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Humans, Ferritins genetics, Ferritins metabolism, Iron metabolism, Iron Overload diagnosis, and Iron Overload genetics

Hyperferritinaemia is a common laboratory finding that is often associated with metabolic dysfunction and fatty liver. Metabolic hyperferritinaemia reflects alterations in iron metabolism that facilitate iron accumulation in the body and is associated with an increased risk of cardiometabolic and liver diseases. Genetic variants that modulate iron homeostasis and tissue levels of iron are the main determinants of serum levels of ferritin in individuals with metabolic dysfunction, raising the hypothesis that iron accumulation might be implicated in the pathogenesis of insulin resistance and the related organ damage. However, validated criteria for the non-invasive diagnosis of metabolic hyperferritinaemia and the staging of iron overload are still lacking, and there is no clear evidence of a benefit for iron depletion therapy. Here, we provide an overview of the literature on the relationship between hyperferritinaemia and iron accumulation in individuals with metabolic dysfunction, and on the associated clinical outcomes. We propose an updated definition and a provisional staging system for metabolic hyperferritinaemia, which has been agreed on by a multidisciplinary global panel of expert researchers. The goal is to foster studies into the epidemiology, genetics, pathophysiology, clinical relevance and treatment of metabolic hyperferritinaemia, for which we provide suggestions on the main unmet needs, optimal design and clinically relevant outcomes.
(© 2023. Springer Nature Limited.)

Animals, Insecta, Predatory Behavior, Larva, Nymph, Chenopodium quinoa, Heteroptera, and Aphids

In recent years, Liorhyssus hyalinus (Fabricius) (Hemiptera: Rhopalidae) and Nysius simulans Stål (Hemiptera: Lygaeidae) have emerged as important pests of quinoa in Peru, when the crop started to be cultivated at relatively low elevations. The potential of the native lacewing Chrysoperla externa (Hagen) (Neuroptera: Chrysopidae) was evaluated as a biological control agent of these two pest species. Prey consumption on all immature stages of L. hyalinus and N. simulans was assessed, as well as development on first instars of these heteropterans and eggs of Sitotroga cerealella (Olivier) (Lepidoptera: Pyralidae) as a factitious prey. In addition, prey preference was examined in the absence and presence of a preferred prey, Macrosiphum euphorbiae (Thomas) (Hemiptera: Aphididae). Larvae of the predator were not able to feed on L. hyalinus eggs, but they effectively did on N. simulans eggs as well as on all nymphal instars of both species. Nymphs of L. hyalinus were less suitable prey for larval development of C. externa than eggs of S. cerealella, whereas N. simulans was overall an unsuitable prey. There was a clear prey preference of C. externa for aphids over the two heteropteran species, as well as a preference for N. simulans over L. hyalinus. The predation rates in this study indicate the potential of C. externa as a predator of these heteropteran pests that can play a role in both conservation and augmentation biological control programs.
(© 2022. Sociedade Entomológica do Brasil.)

BROWN marmorated stink bug, PREDATION, HEMIPTERA, STINKBUGS, PARASITISM, and LAURACEAE

The invasive brown marmorated stink bug, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae), is a polyphagous pest that disperses from non-crop host plants into crops in search of food. Sassafras trees (Sassafras albidum (Nutt.) Nees; Lauraceae) are found commonly in woodland habitats in the southeastern US and may therefore be a potential host. The main objective of this 2-yr study was to determine if sassafras serves as a host plant for this pest in woodland habitats adjacent to crops in Prattville, Alabama, and Byron, Georgia, USA. Each yr pheromone-baited traps were deployed in the canopy of sassafras trees to capture H. halys. We also evaluated parasitism and predation of H. halys sentinel egg masses by native parasitoids and predators in sassafras. Halyomorpha halys adult males and females as well as second through fifth instars were captured in traps and observed in sassafras trees over the season at both locations each yr of the study. Trissolcus euschisti Ashmead (Hymenoptera: Scelionidae) (67.7%) and Anastatus reduvii (Howard) (Hymenoptera: Eupelmidae) (18.3%) were the primary parasitoid species that emerged from H. halys sentinel egg masses. Stylet sucking (62.3%) and chewing (32.0%) were the primary types of predation on H. halys eggs. We conclude that sassafras is a reproductive host plant for H. halys, and native natural enemies prey on and parasitize H. halys egg masses in this host plant. La chinche hedionda invasora marrón marmolada, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae), es una plaga polífaga que se dispersa de plantas hospedantes no cultivadas a los cultivos en busca de alimento. Se les encuentran en los árboles de sasafrás (Sassafras albidum [Nutt.] Nees; Lauraceae) comúnmente en hábitats boscosos del sureste de los EE. UU. y por lo tanto este puede ser un hospedero potencial. El objetivo principal de este estudio de 2 años fue determinar si el sasafrás sirve como planta hospedera para esta plaga en hábitats boscosos adyacentes a cultivos en Prattville, Alabama, y Byron, Georgia, EE. UU. Cada año, se colocaron trampas cebadas con feromonas en el dosel de los árboles de sasafrás para capturar H. halys. También evaluamos el parasitismo y la depredación de masas de huevos centinela de H. halys por parasitoides nativos y depredadores en sasafrás. Se capturaron machos y hembras adultos así como ninfas del segundo al quinto estadio de Halyomorpha halys en las trampas, y se observaron en árboles de sasafrás durante la temporada en ambos lugares cada año del estudio. Trissolcus euschisti Ashmead (Hymenoptera: Scelionidae) (67,7%) y Anastatus reduvii (Howard) (Hymenoptera: Eupelmidae) (18,3%) fueron las principales especies de parasitoides que emergieron de las masas de huevos centinela de H. halys. La succión por los estiletes (62,3%) y la masticación (32,0%) fueron las principales clases de depredación sobre los huevos de H. halys. Concluimos que el sasafrás es una planta hospedera reproductiva para H. halys, y los enemigos naturales nativos se alimentan y parasitan las masas de huevos de H. halys en esta planta hospedera. [ABSTRACT FROM AUTHOR]

BROWN marmorated stink bug, STINKBUGS, PARASITISM, PREDATION, and HEMIPTERA

Stink bugs, including Halyomorpha halys (Stål) and Nezara viridula (L.), are agricultural pests that feed on fruit in a variety of crops. Monitoring predation and parasitism of stink bug egg masses furthers our understanding of potential biological control tactics. However, best practices for laboratory and field assessments of parasitism and predation of egg masses require further attention. We carried out a series of laboratory and field experiments to test whether parasitism and predation for three types of sentinel H. halys egg masses, fresh, frozen, and refrigerated, varied in agricultural commodities. In addition, we asked if predation and parasitism differed between sentinel and naturally occurring H. halys and N. viridula egg masses in soybean. In the laboratory, more H. halys eggs were parasitized by Trissolcus euschisti (Ashmead) (Hymenoptera: Scelionidae) if they were frozen or refrigerated compared to fresh eggs. Similarly, in the field, parasitism was higher for frozen egg masses than fresh. In 2018 and 2019, H. halys natural egg masses had higher parasitism and lower predation compared to sentinel egg masses in soybean. In a paired field test during 2020 and 2021, there was no difference in parasitism between H. halys natural and sentinel eggs, but much higher incidence of parasitism was detected in natural N. viridula egg masses than sentinel eggs. Collecting natural egg masses is the best methodology for field assessment of parasitism of stink bug egg masses; however, if natural egg masses are not easily available, deploying refrigerated sentinel egg masses is a good alternative. [ABSTRACT FROM AUTHOR]

Child, Humans, Fusidic Acid therapeutic use, Fusidic Acid pharmacology, Methicillin, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Netherlands epidemiology, Staphylococcus aureus, Disease Outbreaks, Microbial Sensitivity Tests, Methicillin-Resistant Staphylococcus aureus, Impetigo drug therapy, Impetigo epidemiology, Staphylococcal Infections drug therapy, and Staphylococcal Infections epidemiology

In this retrospective observational study, we analysed a community outbreak of impetigo with meticillin-resistant Staphylococcus aureus (MRSA), with additional resistance to fusidic acid (first-line treatment). The outbreak occurred between June 2018 and January 2020 in the eastern part of the Netherlands with an epidemiological link to three cases from the north-western part. Forty nine impetigo cases and eight carrier cases were identified, including 47 children. All but one impetigo case had community-onset of symptoms. Pharmacy prescription data for topical mupirocin and fusidic acid and GP questionnaires suggested an underestimated outbreak size. The 57 outbreak isolates were identified by the Dutch MRSA surveillance as MLVA-type MT4627 and sequence type 121, previously reported only once in 2014. Next-generation sequencing revealed they contained a fusidic acid resistance gene, exfoliative toxin genes and an epidermal cell differentiation inhibitor gene. Whole-genome multilocus sequence typing revealed genetic clustering of all 19 sequenced isolates from the outbreak region and isolates from the three north-western cases. The allelic distances between these Dutch isolates and international isolates were high. This outbreak shows the appearance of community-onset MRSA strains with additional drug resistance and virulence factors in a country with a low prevalence of antimicrobial resistance.

Background: Thrombosis is a frequent and severe complication in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Lupus anticoagulant (LA) is a strong acquired risk factor for thrombosis in various diseases and is frequently observed in patients with COVID-19. Whether LA is associated with thrombosis in patients with severe COVID-19 is currently unclear.
Objective: To investigate if LA is associated with thrombosis in critically ill patients with COVID-19.
Patients/methods: The presence of LA and other antiphospholipid antibodies was assessed in patients with COVID-19 admitted to the ICU. LA was determined with dilute Russell's viper venom time (dRVVT) and LA-sensitive activated partial thromboplastin time (aPTT) reagents.
Results: Of 169 patients with COVID-19, 116 (69%) tested positive for at least one antiphospholipid antibody upon admission to the ICU. Forty (24%) patients tested positive for LA; of whom 29 (17%) tested positive with a dRVVT, 19 (11%) tested positive with an LA-sensitive aPTT, and 8 (5%) tested positive on both tests. Fifty-eight (34%) patients developed thrombosis after ICU admission. The odds ratio (OR) for thrombosis in patients with LA based on a dRVVT was 2.5 (95% confidence interval [CI], 1.1-5.7), which increased to 4.5 (95% CI, 1.4-14.3) in patients at or below the median age in this study (64 years). LA positivity based on a dRVVT or LA-sensitive aPTT was only associated with thrombosis in patients aged less than 65 years (OR, 3.8; 95% CI, 1.3-11.4) and disappeared after adjustment for C-reactive protein.
Conclusion: Lupus anticoagulant on admission is strongly associated with thrombosis in critically ill patients with COVID-19, especially in patients aged less than 65 years.
(© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

MISSENSE mutation, GENETIC variation, LIGAND-gated ion channels, NEUROTRANSMITTER receptors, AMPA receptors, and NEURAL development

GRIA1 encodes the GluA1 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors, which are ligand-gated ion channels that act as excitatory receptors for the neurotransmitter L -glutamate (Glu). AMPA receptors (AMPARs) are homo- or heteromeric protein complexes with four subunits, each encoded by different genes, GRIA1 to GRIA4. Although GluA1-containing AMPARs have a crucial role in brain function, the human phenotype associated with deleterious GRIA1 sequence variants has not been established. Subjects with de novo missense and nonsense GRIA1 variants were identified through international collaboration. Detailed phenotypic and genetic assessments of the subjects were carried out and the pathogenicity of the variants was evaluated in vitro to characterize changes in AMPAR function and expression. In addition, two Xenopus gria1 CRISPR-Cas9 F 0 models were established to characterize the in vivo consequences. Seven unrelated individuals with rare GRIA1 variants were identified. One individual carried a homozygous nonsense variant (p.Arg377Ter), and six had heterozygous missense variations (p.Arg345Gln, p.Ala636Thr, p.Ile627Thr, and p.Gly745Asp), of which the p.Ala636Thr variant was recurrent in three individuals. The cohort revealed subjects to have a recurrent neurodevelopmental disorder mostly affecting cognition and speech. Functional evaluation of major GluA1-containing AMPAR subtypes carrying the GRIA1 variant mutations showed that three of the four missense variants profoundly perturb receptor function. The homozygous stop-gain variant completely destroys the expression of GluA1-containing AMPARs. The Xenopus gria1 models show transient motor deficits, an intermittent seizure phenotype, and a significant impairment to working memory in mutants. These data support a developmental disorder caused by both heterozygous and homozygous variants in GRIA1 affecting AMPAR function. [ABSTRACT FROM AUTHOR]

Animals, Biology, Diet, Female, Nymph growth development, Ovum, Heteroptera growth development, Temperature, and Zea mays

When quinoa, Chenopodium quinoa Willd., is cultivated in South America outside of its Andean origin, the heteropterans Liorhyssus hyalinus (Fabricius) and Nysius simulans Stål may emerge as important pests. Here we studied the development and reproduction of both species at different constant temperatures in the laboratory. Egg and nymphal development were investigated at 18, 22, 26, 30, 34, and 36°C. For both species, egg incubation time significantly decreased as the temperature increased. Nymphs did not successfully develop at 18°C and the total nymphal time significantly decreased as the temperature increased from 22 to 36°C. Based on a linear day-degree (DD) model, the lower developmental threshold (LDT) temperatures for eggs and nymphs were estimated to be 16.0 and 17.9°C for L. hyalinus, and 16.1 and 19.7°C for N. simulans, respectively. Thermal requirements for egg and nymphal development were 68.6 and 114.8 DD for L. hyalinus, and 77.7 and 190.3 DD for N. simulans, respectively. Reproduction and adult longevity were studied at 22, 26, 30, and 34°C. For both species preoviposition time decreased as temperature increased, and the oviposition period was longest at 26°C. The highest fecundity and egg viability were observed at 30°C, whereas longevities were higher at 22-26°C than at 30-34°C. As the lowest tested temperatures were not suitable to both heteropterans and 30°C was found to be the optimal temperature for development and reproduction, peak densities are expected in warm areas and seasons.
(© The Author(s) 2022. Published by Oxford University Press on behalf of Entomological Society of America.)

STINKBUGS, BROWN marmorated stink bug, HYMENOPTERA, OVIPARITY, BIOLOGICAL pest control agents, GREENBUG, and HOSTS of parasitoids

• We tested the physiological host ranges of an introduced biocontrol agent (T. basalis) and native parasitoid (T. oenone). • T. basalis attacks and develops in all nine pentatomid taxa we tested. • The native T. oenone attacks and develops in seven out of eight pentatomid species we tested. • Parasitism efficiencies were high for all treatments (>60%). Retrospective host range testing is essential for understanding the physiological host range of introduced biological control agents (BCAs) and updating forecasts of non-target risks. It is especially important to conduct this work if there was no host range testing prior to release of the agent. Trissolcus basalis Wollaston was released in New Zealand in 1949 against green vegetable bug (Nezara viridula [L.]), but host range testing was never undertaken, and subsequent work in the 1960s was only of a qualitative nature and remains incomplete. The host-parasitoid complex between New Zealand pentatomids, T. basalis , and the native pentatomid parasitoid Trissolcus oenone Dodd, is therefore poorly understood. We conducted no-choice oviposition tests between the two resident Trissolcus species and all available New Zealand pentatomid species to characterise the physiological (=fundamental) host ranges of these parasitoids. We present the results of the first retrospective host-specificity study on T. basalis in New Zealand. Our results show T. basalis attacks and develops in all nine pentatomid taxa we exposed it to (including the endemic alpine species Hypsithocus hudsonae Bergroth), while T. oenone attacks and develops in seven out of eight pentatomid species we tested it against (and its capacity to attack H. hudsonae remains unknown). Parasitism efficiencies for all treatments exceeded 60%, while development times were similar for both parasitoids regardless of host. We discuss the importance of physiological host range testing for understanding potential non-target effects. Trissolcus japonicus Ashmead (Hymenoptera: Scelionidae) was recently approved for release in New Zealand against brown marmorated stink bug Halyomorpha halys Stål (Hemiptera: Pentatomidae), subject to its potential establishment, and we examine our results in the context of potential competition between introduced parasitoids for non-target species. [ABSTRACT FROM AUTHOR]

MEDICAL personnel, BLOOD testing, COVID-19 testing, SICK leave, and HOSPITALS

Background: COVID-19 is an ongoing pandemic leading to exhaustion of the hospital care system. Our health care system has to deal with a high level of sick leave of health care workers (HCWs) with COVID-19 related complaints, in whom an infection with SARS-CoV-2 has to be ruled out before they can return back to work. The aim of the present study is to investigate if the recently described CoLab-algorithm can be used to exclude COVID-19 in a screening setting of HCWs. Methods: In the period from January 2021 till March 2021, HCWs with COVID-19-related complaints were prospectively collected and included in this study. Next to the routinely performed SARS-CoV-2 RT-PCR, using a set of naso- and oropharyngeal swab samples, two blood tubes (one EDTA- and one heparin-tube) were drawn for analysing the 10 laboratory parameters required for running the CoLab-algorithm. Results: In total, 726 HCWs with a complete CoLab-laboratory panel were included in this study. In this group, 684 HCWs were tested SARS-CoV-2 RT-PCR negative and 42 cases RT-PCR positive. ROC curve analysis showed an area under the curve (AUC) of 0.853 (95% CI: 0.801–0.904). At a safe cut-off value for excluding COVID-19 of -6.525, the sensitivity was 100% with a specificity of 34% (95% CI: 21 to 49%). No SARS-CoV-2 RT-PCR cases were missed with this cut-off and COVID-19 could be safely ruled out in more than one third of HCWs. Conclusion: The CoLab-score is an easy and reliable algorithm that can be used for screening HCWs with COVID-19 related complaints. A major advantage of this approach is that the results of the score are available within 1 hour after collecting the samples. This results in a faster return to labour process of a large part of the COVID-19 negative HCWs (34%), next to a reduction in RT-PCR tests (reagents and labour costs) that can be saved. [ABSTRACT FROM AUTHOR]

Cross-Sectional Studies, Disease Progression, Humans, Phenotype, Leukoencephalopathies diagnostic imaging, and Leukoencephalopathies genetics

Purpose: Recent reports of individuals with cytoplasmic transfer RNA (tRNA) synthetase-related disorders have identified cases with phenotypic variability from the index presentations. We sought to assess phenotypic variability in individuals with AARS1-related disease.
Methods: A cross-sectional survey was performed on individuals with biallelic variants in AARS1. Clinical data, neuroimaging, and genetic testing results were reviewed. Alanyl tRNA synthetase (AlaRS) activity was measured in available fibroblasts.
Results: We identified 11 affected individuals. Two phenotypic presentations emerged, one with early infantile-onset disease resembling the index cases of AARS1-related epileptic encephalopathy with deficient myelination (n = 7). The second (n = 4) was a later-onset disorder, where disease onset occurred after the first year of life and was characterized on neuroimaging by a progressive posterior predominant leukoencephalopathy evolving to include the frontal white matter. AlaRS activity was significantly reduced in five affected individuals with both early infantile-onset and late-onset phenotypes.
Conclusion: We suggest that variants in AARS1 result in a broader clinical spectrum than previously appreciated. The predominant form results in early infantile-onset disease with epileptic encephalopathy and deficient myelination. However, a subgroup of affected individuals manifests with late-onset disease and similarly rapid progressive clinical decline. Longitudinal imaging and clinical follow-up will be valuable in understanding factors affecting disease progression and outcome.
(© 2021. The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.)

STINKBUGS, OLIVE fly, OLIVE, FRUIT development, BROWN marmorated stink bug, INTRODUCED organisms, and LEAFHOPPERS

Olives, Olea europaea L. (Oleaceae), are an emerging commercial crop in Florida; however, potential arthropod threats during olive tree establishment and fruit development remain uncharacterized. Two potential pests that may threaten olive fruit production directly are native and invasive pentatomid stink bugs, which are important pest species of many crops in the southeast, and the invasive olive fruit fly, Bactrocera oleae (Gmelin) (Diptera: Tephritidae),which is not known to be established in Florida. Monitoring for stink bugs during fruit maturation was done using dual funnel tube traps baited with stink bug lures. Yellow sticky card traps baited with food and pheromone lures were used to monitor for the olive fruit fly. Both trap types were placed in tree canopies in 4 North Central Florida olive groves during the anticipated fruit development period for 2 growing seasons. Whereas neither of the invasive species targeted (Halyomorpha halys Stål [Hemiptera: Pentatomidae] or B. oleae) were detected, several other potential pests were identified including brown stink bugs (Euschistus spp.; Hemiptera: Pentatomidae), glassy winged sharpshooters, Homalodisca vitripennis Germar (Hemiptera: Cicadellidae), and grasshoppers. No fruit damage attributable to arthropod pests was detected although fruit production was very low with limited samples. These results contribute to awareness of potential pests that may jeopardize olive fruit production and aid in the future studies to develop effective monitoring activities for Florida growers. [ABSTRACT FROM AUTHOR]

Anti-Bacterial Agents pharmacology, Geography, Medical, History, 21st Century, Humans, Microbial Sensitivity Tests, Multilocus Sequence Typing, Netherlands epidemiology, Phylogeny, Pilot Projects, Pseudomonas Infections history, Pseudomonas aeruginosa classification, Pseudomonas aeruginosa drug effects, Pseudomonas aeruginosa isolation purification, Public Health Surveillance, beta-Lactam Resistance, beta-Lactamases biosynthesis, Disease Outbreaks, Pseudomonas Infections epidemiology, Pseudomonas Infections microbiology, Pseudomonas aeruginosa genetics, and beta-Lactamases genetics

Verona Integron-encoded Metallo-beta-lactamase (VIM) is the most frequently-encountered carbapenemase in the healthcare-related pathogen Pseudomonas aeruginosa. In the Netherlands, a low-endemic country for antibiotic-resistant bacteria, no national surveillance data on the prevalence of carbapenemase-producing P. aeruginosa (CPPA) was available. Therefore, in 2016, a national surveillance pilot study was initiated to investigate the occurrence, molecular epidemiology, genetic characterization, and resistomes of CPPA among P. aeruginosa isolates submitted by medical microbiology laboratories (MMLs) throughout the country. From 1221 isolates included in the study, 124 (10%) produced carbapenemase (CIM-positive); of these, the majority (95, 77%) were positive for the bla VIM gene using PCR. Sequencing was performed on 112 CIM-positive and 56 CIM-negative isolates (n = 168), and genetic clustering revealed that 75/168 (45%) isolates were highly similar. This genetic cluster, designated Group 1, comprised isolates that belonged to high-risk sequence type ST111/serotype O12, had similar resistomes, and all but two carried the bla VIM-2 allele on an identical class 1 integron. Additionally, Group 1 isolates originated from around the country (i.e. seven provinces) and from multiple MMLs. In conclusion, the Netherlands had experienced a nationwide, inter-institutional, clonal outbreak of VIM-2-producing P. aeruginosa for at least three years, which this pilot study was crucial in identifying. A structured, national surveillance program is strongly advised to monitor the spread of Group 1 CPPA, to identify emerging clones/carbapenemase genes, and to detect transmission in and especially between hospitals in order to control current and future outbreaks.
(© 2021. The Author(s).)

STINKBUGS, BROWN marmorated stink bug, CYTOCHROME oxidase, GENETIC variation, and HEMIPTERA

The arrival, establishment and pest status of Halyomorpha halys in Europe and non-native countries in Asia have been well-documented, with thorough characterisation of the genetic diversity and occurrence of cytochrome oxidase I (COI) haplotypes in Switzerland, France, Hungary, Italy and Greece. However, a number of gaps exist in terms of the characterisation of the haplotype diversity and occurrence of H. halys along the invasion front that covers eastern Europe, western and central Asia. To contribute towards filling this gap, the COI haplotype diversity and distribution were investigated for H. halys collected in Serbia, Ukraine, Russia, Georgia and Kazakhstan. A total of 646 specimens were analysed and five haplotypes were found (H1, H3, H8, H33 and H80). Haplotype H1 was present in all five countries investigated and was the only haplotype detected amongst > 500 specimens collected from Ukraine, Russia and Georgia. H1 (82%) was the dominant haplotype found in Kazakhstan, alongside H3 (18%). In contrast to the low or no diversity observed in these four countries, Serbia had higher haplotype diversity and was represented by five haplotypes. Although H3 was dominant (47%) in Serbia, H1 was also prevalent (40%); the remaining haplotypes (H8, H33 and H80) were minor contributors (1-11%) to the haplotype composition. The results are discussed in context with other known populations in neighbouring countries and patterns of haplotype diversity indicate the movement of successful invasive populations in Europe to generate secondary invasions along the eastern front of the invasion in Eurasia. Possible scenarios regarding the spread of particular haplotypes in these regions are discussed, along with suggestions for future research to fill existing gaps. [ABSTRACT FROM AUTHOR]

BROWN marmorated stink bug, PREDATORY insects, ORCHARDS, ANTS, HYMENOPTERA, and PREDATORY animals

In recent years, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae, Cappaeini) has become an invasive pest in North America and Europe, where it caused extensive damage to agriculture, resulting in great economic losses. Evaluating the potential of native predators in the invaded areas, ants might represent good candidates thanks to their biology, ecology, and behavior. In Italy, H. halys proved to be the top key pest in pear orchards, where the black garden ant, Lasius niger (L.) (Hymenoptera: Formicidae, Lasiini), is the most abundant ant species. The aim of this study was to evaluate the predatory ability of L. niger on the eggs and on all the juvenile instars of H. halys under laboratory conditions. The results indicate that L. niger significantly reduces the survival of the second and third nymphal instars by 56 and 58%, respectively, but it is unable to reduce the egg hatching and the survival of the first, fourth, and fifth instars. Our preliminary results obtained in laboratory conditions suggest a possible role of the ant L. niger in controlling H. halys invasion mainly acting on the smaller and more mobile nymphal stages. The effective role of this species as potential biocontrol agents of H. halys in fruit orchards in association with other ant species as well as with other predatory insects is discussed. [ABSTRACT FROM AUTHOR]

We report the first detection of Trissolcus mitsukurii in France. More than 1860 sentinel egg masses of Halyomorpha halys (BMSB) were exposed in the field during the 2018-2020 period, and 12 specimens of T. mitsukurii emerged from one egg mass. Their taxonomic identification was confirmed both by morphological and molecular analysis. Trissolcus mitsukurii , similar to T. japonicus , is an egg parasitoid of BMSB in its area of origin in Asia, and both species are considered to be candidates for a classical biological control strategy against BMSB. Trissolcus mitsukurii was previously recorded in Italy where it is well established and widespread, and this may be the source of the French population. Possible permanent establishment and dispersion of T. mitsukurii in France should be monitored with emphasis on its potential effect on BMSB populations.

Adolescent, Adult, Aged, Amylases blood, Biopsy, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Dose-Response Relationship, Drug, Double-Blind Method, Female, Glucagon-Like Peptides adverse effects, Humans, Injections, Subcutaneous, Lipase blood, Liver pathology, Liver Cirrhosis drug therapy, Liver Cirrhosis etiology, Liver Cirrhosis pathology, Male, Middle Aged, Non-alcoholic Fatty Liver Disease blood, Non-alcoholic Fatty Liver Disease complications, Non-alcoholic Fatty Liver Disease pathology, Young Adult, Glucagon-Like Peptides administration dosage, and Non-alcoholic Fatty Liver Disease drug therapy

Background: Nonalcoholic steatohepatitis (NASH) is a common disease that is associated with increased morbidity and mortality, but treatment options are limited. The efficacy and safety of the glucagon-like peptide-1 receptor agonist semaglutide in patients with NASH is not known.
Methods: We conducted a 72-week, double-blind phase 2 trial involving patients with biopsy-confirmed NASH and liver fibrosis of stage F1, F2, or F3. Patients were randomly assigned, in a 3:3:3:1:1:1 ratio, to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg or corresponding placebo. The primary end point was resolution of NASH with no worsening of fibrosis. The confirmatory secondary end point was an improvement of at least one fibrosis stage with no worsening of NASH. The analyses of these end points were performed only in patients with stage F2 or F3 fibrosis; other analyses were performed in all the patients.
Results: In total, 320 patients (of whom 230 had stage F2 or F3 fibrosis) were randomly assigned to receive semaglutide at a dose of 0.1 mg (80 patients), 0.2 mg (78 patients), or 0.4 mg (82 patients) or to receive placebo (80 patients). The percentage of patients in whom NASH resolution was achieved with no worsening of fibrosis was 40% in the 0.1-mg group, 36% in the 0.2-mg group, 59% in the 0.4-mg group, and 17% in the placebo group (P<0.001 for semaglutide 0.4 mg vs. placebo). An improvement in fibrosis stage occurred in 43% of the patients in the 0.4-mg group and in 33% of the patients in the placebo group (P = 0.48). The mean percent weight loss was 13% in the 0.4-mg group and 1% in the placebo group. The incidence of nausea, constipation, and vomiting was higher in the 0.4-mg group than in the placebo group (nausea, 42% vs. 11%; constipation, 22% vs. 12%; and vomiting, 15% vs. 2%). Malignant neoplasms were reported in 3 patients who received semaglutide (1%) and in no patients who received placebo. Overall, neoplasms (benign, malignant, or unspecified) were reported in 15% of the patients in the semaglutide groups and in 8% in the placebo group; no pattern of occurrence in specific organs was observed.
Conclusions: This phase 2 trial involving patients with NASH showed that treatment with semaglutide resulted in a significantly higher percentage of patients with NASH resolution than placebo. However, the trial did not show a significant between-group difference in the percentage of patients with an improvement in fibrosis stage. (Funded by Novo Nordisk; ClinicalTrials.gov number, NCT02970942.).
(Copyright © 2020 Massachusetts Medical Society.)

Adolescent, Autism Spectrum Disorder genetics, Autism Spectrum Disorder pathology, Child, Child, Preschool, Chromosome Deletion, Chromosome Disorders physiopathology, DNA Methylation genetics, Epigenesis, Genetic genetics, Female, Haploinsufficiency genetics, Humans, Intellectual Disability genetics, Intellectual Disability physiopathology, Male, Neurodevelopmental Disorders genetics, Neurodevelopmental Disorders physiopathology, Phenotype, Young Adult, Chromosome Disorders genetics, Chromosomes, Human, Pair 1 genetics, Chromosomes, Human, X genetics, DNA-Binding Proteins genetics, and RNA-Binding Proteins genetics

Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms. SPEN encodes a transcriptional repressor commonly deleted in proximal del1p36 syndrome and is located centromeric to the proximal 1p36 critical region. Here, we used clinical data from 34 individuals with truncating variants in SPEN to define a neurodevelopmental disorder presenting with features that overlap considerably with those of proximal del1p36 syndrome. The clinical profile of this disease includes developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI, especially in females. SPEN also emerges as a relevant gene for del1p36 syndrome by co-expression analyses. Finally, we show that haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females, providing further evidence of a specific contribution of the protein to the epigenetic control of this chromosome, and a paradigm of an X chromosome-specific episignature that classifies syndromic traits. We conclude that SPEN is required for multiple developmental processes and SPEN haploinsufficiency is a major contributor to a disorder associated with deletions centromeric to the previously established 1p36 critical regions.
(Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Adult, Antineoplastic Agents, Hormonal therapeutic use, Biomarkers, Tumor metabolism, Breast Neoplasms drug therapy, Female, Humans, Lymphatic Metastasis, Middle Aged, Neoplastic Stem Cells pathology, Prognosis, Randomized Controlled Trials as Topic, Retrospective Studies, Survival Rate, Adaptor Proteins, Vesicular Transport metabolism, Breast Neoplasms metabolism, Breast Neoplasms pathology, Neoplastic Stem Cells metabolism, Progranulins metabolism, and Tamoxifen therapeutic use

Background: The growth factor progranulin has been implicated in numerous biological processes such as wound healing, inflammation and progressive tumorigenesis. Both progranulin and its receptor sortilin are known to be highly expressed in subgroups of breast cancer and have been associated with various clinical properties including tamoxifen resistance. Recent data further suggest that progranulin, via its receptor sortilin, drives breast cancer stem cell propagation in vitro and increases metastasis formation in an in vivo breast cancer xenograft model. In this retrospective biomarker analysis, we aimed to determine whether tumor co-expression of progranulin and sortilin has prognostic and treatment predictive values for breast cancer patients.
Methods: We explored how co-expression of progranulin and sortilin was associated with established clinical markers by analyzing a tissue microarray including 560 randomized premenopausal breast cancer patients receiving either 2 years of tamoxifen treatment or no adjuvant treatment, with a median follow-up time of 28 years. Breast cancer-specific survival was analyzed using Kaplan-Meier and Cox Proportional Hazards regression models to assess the prognostic and predictive value of progranulin and sortilin in relation to known clinical markers.
Results: Co-expression of progranulin and sortilin was observed in 20% of the breast cancer samples. In untreated patients, prognostic considerations could be detailed separately from treatment prediction and the high progranulin and sortilin expressing subgroup was significantly associated with breast cancer-specific death in multivariable analyses (HR=2.188, CI: 1.317-3.637, p=0.003) along with tumor size, high tumor grade and lymph node positivity. When comparing the untreated patients with tamoxifen treated patients in the ERα positive subgroup, co-expression of progranulin and sortilin was not linked to tamoxifen resistance.
Conclusion: Data suggest that co-expression of progranulin and its receptor sortilin is a novel prognostic biomarker combination identifying a highly malignant subgroup of breast cancer. Importantly, this subpopulation could potentially be targeted with anti-sortilin based therapies.

STINKBUGS, BROWN marmorated stink bug, BIOLOGICAL control of insects, HEMIPTERA, BIOLOGICAL pest control agents, BIOLOGICAL pest control, and INTEGRATED pest control

Invasive stink bugs (Hemiptera: Pentatomidae) are responsible for high economic losses to agriculture on a global scale. The most important species, dating from recent to old invasions, include Bagrada hilaris (Burmeister), Halyomorpha halys (Stål), Piezodorus guildinii (Westwood), Nezara viridula (L.), and Murgantia histrionica (Hahn). Bagrada hilaris, H. halys, and N. viridula are now almost globally distributed. Biological control of these pests faces a complex set of challenges that must be addressed to maintain pest populations below the economic injury level. Several case studies of classical and conservation biological control of invasive stink bugs are reported here. The most common parasitoids in their geographical area of origin are egg parasitoids (Hymenoptera: Scelionidae, Encyrtidae, and Eupelmidae). Additionally, native parasitoids of adult stink bugs (Diptera: Tachinidae) have in some cases adapted to the novel hosts in the invaded area and native predators are known to prey on the various instars. Improving the efficacy of biocontrol agents is possible through conservation biological control techniques and exploitation of their chemical ecology. Moreover, integration of biological control with other techniques, such as behavioural manipulation of adult stink bugs and plant resistance, may be a sustainable pest control method within organic farming and integrated pest management programs. However, additional field studies are needed to verify the efficacy of these novel methods and transfer them from research to application. [ABSTRACT FROM AUTHOR]

BIOLOGICAL weed control, BIOLOGICAL pest control agents, CHRYSOMELIDAE, BEETLES, HYMENOPTERA, and EUCALYPTUS

The solitary larval endoparasitoid Eadya daenerys Ridenbaugh (Hymenoptera: Braconidae) is a proposed biocontrol agent of Paropsis charybdis Stål (Coleoptera: Chrysomelidae, Chrysomelinae), a pest of eucalypts in New Zealand. Eadya daenerys oviposition behaviour was examined in two assay types during host range testing, with the aim of improving ecological host range prediction. No‐choice sequential and two‐choice behavioural observations were undertaken against nine closely related species of New Zealand non‐target beetle larvae, including a native beetle, introduced weed biocontrol agents, and invasive paropsine beetles. No behavioural measure was significantly different between no‐choice and two‐choice tests. In sequential no‐choice assays the order of first presentation (target–non‐target) had no significant effect on the median number of attacks or the attack rate while on the plant. Beetle species was the most important factor. Parasitoids expressed significantly lower on‐plant attack rates against non‐targets compared to target P. charybdis larvae. The median number of attacks was always higher towards target larvae than towards non‐target larvae, except for the phylogenetically closest related non‐target Trachymela sloanei (Blackburn) (Coleoptera: Chrysomelidae, Chrysomelinae). Most non‐target larvae were disregarded upon contact, which suggests that the infrequent attack behaviour observed by two individual E. daenerys against Allocharis nr. tarsalis larvae in two‐choice tests and the frass of Chrysolina abchasica (Weise) was probably abnormal host selection behaviour. Results indicate that E. daenerys is unlikely to attack non‐target species apart from Eucalyptus‐feeding invasive paropsines (Chrysomelinae). Non‐lethal negative impacts upon less preferred non‐target larvae are possible if E. daenerys does attack them in the field; however, this is likely to be rare. [ABSTRACT FROM AUTHOR]

HYMENOPTERA, CURCULIONIDAE, HOMOPTERA, PEST control, INSECT collection & preservation, BEETLES, and HEMIPTERA

The knowledge of the entomological fauna in productive systems is important for the agroecological management since beneficial insects are a key resource for pest management in horticultural systems. Scientific information on the biodiversity present in a given area is essential as well as the ecological function and/or feeding habits of the insects. In Alto Valle de Río Negro and Neuquén, horticultural production systems can be described as highly dependent on chemical inputs for pest management and fertilization. The aim of this study is to carry out an inventory of the biodiversity of some families of Hemiptera, Coleoptera (Curculionidae) and Hymenoptera present in peri-urban and rural farms located in Neuquén and Río Negro, respectively. Insects were collected through pitfall and sweeping net on tomato and pepper crops and the surrounding non-cultivated areas. Idiosystatus Berg (Auchenorrhyncha) was cited for the first time from Argentina. Species cited for the first time from Neuquén: Hemiptera: Auchenorrhyncha: Acanalonia chloris (Berg), Syncharina punctatissima (Signoret), Amplicephalus dubius Linnavuori, Exitianus obscurinervis (Stål), Agalliana ensigera Oman and Bergallia signata (Stål); Hemiptera: Heteroptera: Harmostes (Harmostes) prolixus Stål and Atrachelus (Atrachelus) cinereus (Fabricius); Coleoptera: Curculionidae: Hypurus bertrandi (Perris), Naupactus leucoloma Boheman, Otiorhynchus rugosostriatus (Goeze) and Sitona discoideus Gyllenhal and Hymenoptera: Xylocopa (Neoxylocopa) augusti Lepeletier and Pseudagapostemon (Neagapostemon) singularis Jörgensen. Species cited for the first time from Río Negro: Hemiptera: Auchenorrhyncha: Amplicephalus dubius Linnavuori, Amplicephalus marginellanus Linnavuori, Circulifer tenellus (Baker) and Xerophloea viridis (Fabricius); Hemiptera: Heteroptera: Tupiocoris cucurbitaceus (Spinola), Atrachelus (Atrachelus) cinereus (Fabricius), Dichelops furcatus (Fabricius) and Harmostes (Harmostes) prolixus Stål; Coleptera: Curculionidae: Naupactus xanthographus (Germar) and Hymenoptera: Diadasia pereyrae (Holmberg) and Dialictus autranellus (Vachal). [ABSTRACT FROM AUTHOR]

Adolescent, Animals, Child, Child, Preschool, Drosophila Proteins genetics, Drosophila melanogaster, Female, Genes, Dominant, Genetic Variation, Haploinsufficiency, Humans, Infant, Male, Microscopy, Confocal, Neuroglia metabolism, Neurons metabolism, Protein Binding, Zebrafish, Zebrafish Proteins genetics, Chromosomal Proteins, Non-Histone genetics, Developmental Disabilities genetics, Mutation, Missense, Phenotype, and Tumor Suppressor Proteins genetics

SWI/SNF-related intellectual disability disorders (SSRIDDs) are rare neurodevelopmental disorders characterized by developmental disability, coarse facial features, and fifth digit/nail hypoplasia that are caused by pathogenic variants in genes that encode for members of the SWI/SNF (or BAF) family of chromatin remodeling complexes. We have identified 12 individuals with rare variants (10 loss-of-function, 2 missense) in the BICRA (BRD4 interacting chromatin remodeling complex-associated protein) gene, also known as GLTSCR1, which encodes a subunit of the non-canonical BAF (ncBAF) complex. These individuals exhibited neurodevelopmental phenotypes that include developmental delay, intellectual disability, autism spectrum disorder, and behavioral abnormalities as well as dysmorphic features. Notably, the majority of individuals lack the fifth digit/nail hypoplasia phenotype, a hallmark of most SSRIDDs. To confirm the role of BICRA in the development of these phenotypes, we performed functional characterization of the zebrafish and Drosophila orthologs of BICRA. In zebrafish, a mutation of bicra that mimics one of the loss-of-function variants leads to craniofacial defects possibly akin to the dysmorphic facial features seen in individuals harboring putatively pathogenic BICRA variants. We further show that Bicra physically binds to other non-canonical ncBAF complex members, including the BRD9/7 ortholog, CG7154, and is the defining member of the ncBAF complex in flies. Like other SWI/SNF complex members, loss of Bicra function in flies acts as a dominant enhancer of position effect variegation but in a more context-specific manner. We conclude that haploinsufficiency of BICRA leads to a unique SSRIDD in humans whose phenotypes overlap with those previously reported.
(Copyright © 2020 American Society of Human Genetics. All rights reserved.)

High-Throughput Nucleotide Sequencing, Humans, Klebsiella pneumoniae isolation purification, Netherlands, DNA, Bacterial genetics, Klebsiella Infections microbiology, Klebsiella pneumoniae genetics, and beta-Lactamases genetics

Carbapenemase-producing Klebsiella pneumoniae emerged as a nosocomial pathogen causing morbidity and mortality in patients. For infection prevention it is important to track the spread of K. pneumoniae and its plasmids between patients. Therefore, the major aim was to recapitulate the contents and diversity of the plasmids of genetically related K. pneumoniae strains harboring the beta-lactamase gene bla KPC-2 or bla KPC-3 to determine their dissemination in the Netherlands and the former Dutch Caribbean islands from 2014 to 2019. Next-generation sequencing was combined with long-read third-generation sequencing to reconstruct 22 plasmids. wgMLST revealed five genetic clusters comprised of K. pneumoniae bla KPC-2 isolates and four clusters consisted of bla KPC-3 isolates. KpnCluster-019 bla KPC-2 isolates were found both in the Netherlands and the Caribbean islands, while bla KPC-3 cluster isolates only in the Netherlands. Each K. pneumoniae bla KPC-2 or bla KPC-3 cluster was characterized by a distinct resistome and plasmidome. However, the large and medium plasmids contained a variety of antibiotic resistance genes, conjugation machinery, cation transport systems, transposons, toxin/antitoxins, insertion sequences and prophage-related elements. The small plasmids carried genes implicated in virulence. Thus, implementing long-read plasmid sequencing analysis for K. pneumoniae surveillance provided important insights in the transmission of a KpnCluster-019 bla KPC-2 strain between the Netherlands and the Caribbean.

Anti-Bacterial Agents pharmacology, Bacterial Proteins metabolism, Carbapenem-Resistant Enterobacteriaceae drug effects, Enterobacter cloacae drug effects, Enterobacter cloacae genetics, Enterobacter cloacae isolation purification, Enterobacteriaceae Infections drug therapy, Enterobacteriaceae Infections microbiology, Escherichia coli drug effects, Escherichia coli genetics, Escherichia coli isolation purification, Humans, Interspersed Repetitive Sequences genetics, Klebsiella pneumoniae drug effects, Klebsiella pneumoniae genetics, Klebsiella pneumoniae isolation purification, Meropenem pharmacology, Microbial Sensitivity Tests, Molecular Epidemiology, Netherlands epidemiology, beta-Lactamases metabolism, Bacterial Proteins genetics, Carbapenem-Resistant Enterobacteriaceae genetics, Carbapenem-Resistant Enterobacteriaceae isolation purification, Enterobacteriaceae Infections epidemiology, and beta-Lactamases genetics

Objectives: Carbapenem resistance mediated by mobile genetic elements has emerged worldwide and has become a major public health threat. To gain insight into the molecular epidemiology of carbapenem resistance in The Netherlands, Dutch medical microbiology laboratories are requested to submit suspected carbapenemase-producing Enterobacterales (CPE) to the National Institute for Public Health and the Environment as part of a national surveillance system.
Methods: Meropenem MICs and species identification were confirmed by E-test and MALDI-TOF and carbapenemase production was assessed by the Carbapenem Inactivation Method. Of all submitted CPE, one species/carbapenemase gene combination per person per year was subjected to next-generation sequencing (NGS).
Results: In total, 1838 unique isolates were received between 2014 and 2018, of which 892 were unique CPE isolates with NGS data available. The predominant CPE species were Klebsiella pneumoniae (n = 388, 43%), Escherichia coli (n = 264, 30%) and Enterobacter cloacae complex (n = 116, 13%). Various carbapenemase alleles of the same carbapenemase gene resulted in different susceptibilities to meropenem and this effect varied between species. Analyses of NGS data showed variation of prevalence of carbapenemase alleles over time with bla OXA-48 being predominant (38%, 336/892), followed by bla NDM-1 (16%, 145/892). For the first time in the Netherlands, bla OXA-181 , bla OXA-232 and bla VIM-4 were detected. The genetic background of K. pneumoniae and E. coli isolates was highly diverse.
Conclusions: The CPE population in the Netherlands is diverse, suggesting multiple introductions. The predominant carbapenemase alleles are bla OXA-48 and bla NDM-1 . There was a clear association between species, carbapenemase allele and susceptibility to meropenem.
(Copyright © 2020 National Institute for Public Health and the Environment, Bilthoven, The Netherlands. Published by Elsevier Ltd.. All rights reserved.)

Adolescent, Adult, Aged, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, International Agencies, Male, Mental Disorders etiology, Middle Aged, Monocarboxylic Acid Transporters genetics, Muscular Diseases etiology, Mutation, Neurodevelopmental Disorders etiology, Prognosis, Retrospective Studies, Survival Rate, Symporters genetics, Young Adult, Biomarkers analysis, Mental Disorders pathology, Monocarboxylic Acid Transporters deficiency, Muscular Diseases pathology, Neurodevelopmental Disorders pathology, and Symporters deficiency

Background: Disordered thyroid hormone transport, due to mutations in the SLC16A2 gene encoding monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought to systematically assess the phenotypic characteristics and natural history of patients with MCT8 deficiency.
Methods: We did an international, multicentre, cohort study, analysing retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency followed up in 47 hospitals in 22 countries globally. The key inclusion criterion was genetically confirmed MCT8 deficiency. There were no exclusion criteria. Our primary objective was to analyse the overall survival of patients with MCT8 deficiency and document causes of death. We also compared survival between patients who did or did not attain full head control by age 1·5 years and between patients who were or were not underweight by age 1-3 years (defined as a bodyweight-for-age Z score <-2 SDs or <5th percentile according to WHO definition). Other objectives were to assess neurocognitive function and outcomes, and clinical parameters including anthropometric characteristics, biochemical markers, and neuroimaging findings.
Findings: Between Oct 14, 2014, and Jan 17, 2020, we enrolled 151 patients with 73 different MCT8 (SLC16A2) mutations. Median age at diagnosis was 24·0 months (IQR 12·0-60·0, range 0·0-744·0). 32 (21%) of 151 patients died; the main causes of mortality in these patients were pulmonary infection (six [19%]) and sudden death (six [19%]). Median overall survival was 35·0 years (95% CI 8·3-61·7). Individuals who did not attain head control by age 1·5 years had an increased risk of death compared with patients who did attain head control (hazard ratio [HR] 3·46, 95% CI 1·76-8·34; log-rank test p=0·0041). Patients who were underweight during age 1-3 years had an increased risk for death compared with patients who were of normal bodyweight at this age (HR 4·71, 95% CI 1·26-17·58, p=0·021). The few motor and cognitive abilities of patients did not improve with age, as evidenced by the absence of significant correlations between biological age and scores on the Gross Motor Function Measure-88 and Bayley Scales of Infant Development III. Tri-iodothyronine concentrations were above the age-specific upper limit in 96 (95%) of 101 patients and free thyroxine concentrations were below the age-specific lower limit in 94 (89%) of 106 patients. 59 (71%) of 83 patients were underweight. 25 (53%) of 47 patients had elevated systolic blood pressure above the 90th percentile, 34 (76%) of 45 patients had premature atrial contractions, and 20 (31%) of 64 had resting tachycardia. The most consistent MRI finding was a global delay in myelination, which occurred in 13 (100%) of 13 patients.
Interpretation: Our description of characteristics of MCT8 deficiency in a large patient cohort reveals poor survival with a high prevalence of treatable underlying risk factors, and provides knowledge that might inform clinical management and future evaluation of therapies.
Funding: Netherlands Organisation for Health Research and Development, and the Sherman Foundation.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)

Adolescent, Adult, Age of Onset, Female, Follow-Up Studies, Growth Hormone-Secreting Pituitary Adenoma genetics, Humans, Male, Pituitary Neoplasms genetics, Prognosis, Prospective Studies, Young Adult, Biomarkers analysis, Genetic Testing methods, Growth Hormone-Secreting Pituitary Adenoma diagnosis, Intracellular Signaling Peptides and Proteins genetics, Mass Screening methods, Mutation, and Pituitary Neoplasms diagnosis

Context: Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs).
Objective: To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients.
Design: 12-year prospective, observational study.
Participants & Setting: We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases.
Interventions & Outcome: AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310).
Results: Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650).
Conclusions: Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course.
(© Endocrine Society 2020.)

Sustainable strategies such as classical or augmentative biological control are currently being evaluated for the long-term management of the alien invasive pest Halyomorpha halys (Stål) (Hemiptera: Pentatomidae). A three-year study carried out in northeastern Italy was performed to investigate the distribution and field performance of the H. halys egg parasitoid Trissolcus mitsukurii (Ashmead) (Hymenoptera: Scelionidae), in comparison with other parasitoid species. In the study area, adventive populations of T. mitsukurii were present since 2016, representing the earliest detection of this species in Europe. Trissolcus mitsukurii was the most abundant parasitoid and showed a higher "parasitoid impact" (i.e., number of parasitized eggs over the total number of field-collected eggs) compared to the other species, i.e., Anastatus bifasciatus (Geoffroy) (Hymenoptera: Eupelmidae), Trissolcus basalis (Wollaston) and Trissolcus kozlovi Rjachovskij (Hymenoptera: Scelionidae). The hyperparasitoid Acroclisoides sinicus (Huang and Liao) (Hymenoptera: Pteromalidae) was also recorded. Phylogenetic analysis of T. mitsukurii population distinguished two clades, one covering samples from Italy, Japan and China, the other from South Korea. The present study provides promising results for the biological control of a pest that is having a dramatic impact on a wide range of crops worldwide.

TAMARISKS, ASSASSIN bugs, LIFE history theory, PREDATORY animals, BODY size, and NATURAL history

The harpactorine assassin bug, Zelus tetracanthus (Stål) (Hemiptera: Reduviidae), is an insect predator frequently found in surveys of saltcedar (Tamarix spp.) in Oklahoma. Previous studies in a laboratory showed it could prey on Diorhabda carinulata (Desbrochers) (Coleoptera: Chrysomelidae), a recently introduced biological control agent for Tamarix. An F2 cohort of Z. tetracanthus was reared from egg to adult to measure stage-specific development rates and describe immature stages at 22 ± 1.0°C and 16:8 light:dark hours. The mean times for development of the five instars were 6.96 ± 0.13, 5.18 ± 0.13, 6.94 ± 0.29, 10.92 ± 0.43, and 17.93 ± 0.76 days, respectively. Several anatomical characters to distinguish instars, including body size, body color, and select morphological characters were described. Data from museum collections of Z. tetracanthus suggested the insect has a univoltine life cycle. The development data contrast with a previous description of Z. socius (= Z. tetracanthus) and illustrate the need to further study the variable morphology, natural history, and genetic makeup of the species. [ABSTRACT FROM AUTHOR]

Administration, Oral, Biomarkers analysis, Biopsy, Chenodeoxycholic Acid administration dosage, Chenodeoxycholic Acid therapeutic use, Double-Blind Method, Female, Humans, Liver Function Tests, Male, Middle Aged, Chenodeoxycholic Acid analogs derivatives, and Non-alcoholic Fatty Liver Disease drug therapy

Background: Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH.
Methods: In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6.
Findings: Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group).
Interpretation: Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes.
Funding: Intercept Pharmaceuticals.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)

Animals, Female, Heteroptera physiology, Life Cycle Stages, Solanum lycopersicum parasitology, Male, Pest Control, Biological methods, Biological Control Agents classification, Moths, and Predatory Behavior

Tuta absoluta (Meyrick), a key pest of tomato, is quickly spreading over the world and biological control is considered as one of the control options. Worldwide more than 160 species of natural enemies are associated with this pest, and an important challenge is to quickly find an effective biocontrol agent from this pool of candidate species. Evaluation criteria for control agents are presented, with the advantages they offer for separating potentially useful natural enemies from less promising ones. Next, an aggregate parameter for ranking agents is proposed: the pest kill rate km. We explain why the predator's intrinsic rate of increase cannot be used for comparing the control potential of predators or parasitoids, while km can be used to compare both types of natural enemies. As an example, kill rates for males, females and both sexes combined of three Neotropical mirid species (Campyloneuropsis infumatus (Carvalho), Engytatus varians (Distant) and Macrolophus basicornis (Stål)) were determined, taking all life-history data (developmental times, survival rates, total nymphal and adult predation, sex ratios and adult lifespan) into account. Based on the value for the intrinsic rate of increase (rm) for T. absoluta and for the kill rate km of the predators, we predict that all three predators are potentially able to control the pest, because their km values are all higher than the rm of the pest. Using only km values, we conclude that E. varians is the best candidate for control of T. absoluta on tomato, with C. infumatus ranking second and M. basicornis last.

NILAPARVATA lugens, RICE, INSECT pests, SINGLE nucleotide polymorphisms, FOOD crops, and IDENTIFICATION

Rice is the most important staple food crop, and it feeds more than half of the world population. Brown planthopper (BPH) is a major insect pest of rice that causes 20–80% yield loss through direct and indirect damage. The identification and use of BPH resistance genes can efficiently manage BPH. A molecular marker-based genetic analysis of BPH resistance was carried out using 101 BC1F5 mapping population derived from a cross between a BPH-resistant indica variety Khazar and an elite BPH-susceptible line Huang–Huan–Zhan. The genetic analysis indicated the existence of Mendelian segregation for BPH resistance. A total of 702 high-quality polymorphic single nucleotide polymorphism (SNP) markers, genotypic data, and precisely estimated BPH scores were used for molecular mapping, which resulted in the identification of the BPH38(t) locus on the long arm of chromosome 1 between SNP markers 693,369 and id 10,112,165 of 496.2 kb in size with LOD of 20.53 and phenotypic variation explained of 35.91%. A total of 71 candidate genes were predicted in the detected locus. Among these candidate genes, LOC_Os01g37260 was found to belong to the FBXL class of F-box protein possessing the LRR domain, which is reported to be involved in biotic stress resistance. Furthermore, background analysis and phenotypic selection resulted in the identification of introgression lines (ILs) possessing at least 90% recurrent parent genome recovery and showing superior performance for several agro-morphological traits. The BPH resistance locus and ILs identified in the present study will be useful in marker-assisted BPH resistance breeding programs. [ABSTRACT FROM AUTHOR]

BROWN marmorated stink bug, STINKBUGS, HEMIPTERA, BIOLOGICAL control of insects, and BIOLOGICAL pest control

The Florida predatory stink bug, Euthyrhynchus floridanus L. (Hemiptera: Pentatomidae), is a generalist predator native to North America that feeds on a broad range of lepidopterous and heteropterous key pests in a great diversity of crops and non-crop situations. Feeding tests conducted in the laboratory to determine the most susceptible stage of the brown marmorated stink bug, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae), to third nymphal instar, and male and female E. floridanus, indicated that this predator has great potential for biological control of H. halys nymphs and adult stages. [ABSTRACT FROM AUTHOR]

MELIACEAE, HOST plants, HEMIPTERA, STINKBUGS, and INSECT antifeedants

Currently, the invasive brown marmorated stink bug, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae), is considered an agricultural and nuisance pest in Georgia. The invasive chinaberry tree, Melia azedarach L. (Meliaceae), commonly grows in dense thickets along roadsides, and in woodlands adjacent to agricultural crops across the southeastern USA. Thus, the objective of this study was to determine the potential of M. azedarach to serve as a host plant of H. halys by examining mortality and feeding of first and second instars on M. azedarach leaves vs. carrot (i.e., a control diet), and documenting presence of H. halys on M. azedarach in woodlands at 2 locations in Georgia where this stink bug has become established. Over all sampling dates and locations, the number of H. halys in chinaberry was very low (0.1 per tree), and only 3 late instars and 1 adult were observed feeding on M. azedarach at 1 field site late in the season. Percentage feeding by second instars of H. halys was lower for individuals given M. azedarach leaves vs. those provided with carrot, most likely indicating that compounds in M. azedarach have an antifeeding effect. In fact, mortality for second instars on M. azedarach leaves was very high, and thus we conclude that M. azedarach is an unsuitable host plant for H. halys. [ABSTRACT FROM AUTHOR]

STINKBUGS, INSECT rearing, HOSTS (Biology), AGRICULTURAL pests, BIOLOGICAL pest control agents, and ENCYRTIDAE

The species Ooencyrtus telenomicida (Vassiliev) (Hymenoptera: Encyrtidae) is currently being considered as a candidate for augmentative biological control agent (BCA) against several pests, including Halyomorpha halys (Stål) (Heteroptera: Pentatomidae). Protocols for mass production of a BCA need fundamental information on its biological attributes. Here we tested a possible laboratory host for the rearing of O. telenomicida: the common bug Graphosoma lineatum L. (Heteroptera: Pentatomidae). At tested conditions, O. telenomicida biological parameters were: rm 0.154, offspring production 84.07 specimens/female, sex ratio (% females) 71%, juvenile development time about 16 days, population doubling time 4.52 days, emergence rate about 90%. [ABSTRACT FROM AUTHOR]

Diagnostic Errors statistics numerical data, Escherichia coli isolation purification, Escherichia coli Infections microbiology, Humans, Klebsiella Infections microbiology, Klebsiella pneumoniae isolation purification, Netherlands, Reproducibility of Results, Anti-Bacterial Agents pharmacology, Escherichia coli drug effects, Fosfomycin pharmacology, Klebsiella pneumoniae drug effects, and Microbial Sensitivity Tests methods

Objectives: Fosfomycin susceptibility testing is complicated and prone to error. Before using fosfomycin widely in patients with serious infections, acquisition of WT distribution data and reliable susceptibility testing methods are crucial. In this study, the performance of five methods for fosfomycin testing in the routine laboratory against the reference method was evaluated.
Methods: Ten laboratories collected up to 100 ESBL-producing isolates each (80 Escherichia coli and 20 Klebsiella pneumoniae). Isolates were tested using Etest, MIC test strip (MTS), Vitek2, Phoenix and disc diffusion. Agar dilution was performed as the reference method in a central laboratory. Epidemiological cut-off values (ECOFFs) were determined for each species and susceptibility and error rates were calculated.
Results: In total, 775 E. coli and 201 K. pneumoniae isolates were tested by agar dilution. The ECOFF was 2 mg/L for E. coli and 64 mg/L for K. pneumoniae. Susceptibility rates based on the EUCAST breakpoint of ≤32 mg/L were 95.9% for E. coli and 87.6% for K. pneumoniae. Despite high categorical agreement rates for all methods, notably in E. coli, none of the alternative antimicrobial susceptibility testing methods performed satisfactorily. Due to poor detection of resistant isolates, very high error rates of 23.3% (Etest), 18.5% (MTS), 18.8% (Vitek2), 12.5% (Phoenix) and 12.9% (disc diffusion) for E. coli and 22.7% (Etest and MTS), 16.0% (Vitek2) and 12% (Phoenix) for K. pneumoniae were found. None of the methods adequately differentiated between WT and non-WT populations.
Conclusions: Overall, it was concluded that none of the test methods is suitable as an alternative to agar dilution in the routine laboratory.

Aged, Biomarkers, Bridged-Ring Compounds administration dosage, Bridged-Ring Compounds adverse effects, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Molecular Targeted Therapy, Mutation, Primary Myelofibrosis diagnosis, Primary Myelofibrosis genetics, Primary Myelofibrosis mortality, Protein Kinase Inhibitors administration dosage, Protein Kinase Inhibitors adverse effects, Pyrimidines administration dosage, Pyrimidines adverse effects, Treatment Outcome, Bridged-Ring Compounds therapeutic use, Primary Myelofibrosis drug therapy, Protein Kinase Inhibitors therapeutic use, and Pyrimidines therapeutic use

Myelofibrosis (MF) is a chronic yet progressive myeloid neoplasm in which only a minority of patients undergo curative therapy, hematopoietic stem cell transplantation. Ruxolitinib, a JAK1/2 inhibitor, is the lone therapy approved for MF, offering a clear symptom and spleen benefit at the expense of treatment-related cytopenias. Pacritinib (PAC), a multi-kinase inhibitor with specificity for JAK2, FLT3, and IRAK1 but sparing JAK1, has demonstrated clinical activity in MF with minimal myelosuppression. Due to an FDA-mandated full clinical hold, the randomized phase 3 PERSIST trials were abruptly stopped and PAC was immediately discontinued for all patients. Thirty-three patients benefitting from PAC on clinical trial prior to the hold were allowed to resume therapy on an individual, compassionate-use basis. This study reports the detailed outcomes of 19 of these PAC retreatment patients with a median follow-up of 8 months. Despite a median platelet count of 49 × 10 9 /L at restart of PAC, no significant change in hematologic profile was observed. Grade 3/4 adverse events of epistaxis (n = 1), asymptomatic QT prolongation (n = 1), and bradycardia (n = 1) occurred in three patients within the first 3 months of retreatment. One death due to catheter-associated sepsis occurred. The median time to discontinuation of PAC therapy on compassionate use for all 33 patients was 12.2 (95% CI 8.3-NR) months. PAC retreatment was associated with modest improvement in splenomegaly without progressive myelosuppression and supports the continued development of this agent for the treatment of MF second line to ruxolitinib or in the setting of treatment-limiting thrombocytopenia.

Adolescent, Cell Count, Child, Collagen metabolism, Cytokines biosynthesis, Cytokines genetics, Female, Gene Expression Regulation, Humans, Male, Muscle Fibers, Skeletal pathology, RNA, Ribosomal genetics, Real-Time Polymerase Chain Reaction, Ribosomes genetics, Ribosomes pathology, Satellite Cells, Skeletal Muscle pathology, Brain Injuries pathology, Cerebral Palsy pathology, Extracellular Matrix pathology, Muscle, Skeletal pathology, and RNA, Ribosomal biosynthesis

Introduction: Children with cerebral palsy (CP) and acquired brain injury (ABI) commonly develop muscle contractures with advancing age. An underlying growth defect contributing to skeletal muscle contracture formation in CP/ABI has been suggested.
Methods: The biceps muscles of children and adolescents with CP/ABI (n = 20) and typically developing controls (n = 10) were investigated. We used immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blotting to assess gene expression relevant to growth and size homeostasis.
Results: Classical pro-inflammatory cytokines and genes involved in extracellular matrix (ECM) production were elevated in skeletal muscle of children with CP/ABI. Intramuscular collagen content was increased and satellite cell number decreased and this was associated with reduced levels of RNA polymerase I transcription factors, 45s pre-rRNA and 28S rRNA.
Discussion: The present study provides novel data suggesting a role for pro-inflammatory cytokines and reduced ribosomal production in the development/maintenance of muscle contractures, possibly underlying stunted growth and perimysial ECM expansion. Muscle Nerve 58: 277-285, 2018.
(© 2018 Wiley Periodicals, Inc.)

The work's aims were to identify both harmful and helpful insect species for safflower crop and to study their distribution along time in relation to plant phenological state. The insect species identified as harmful were: Uroleucon jaceae L., Capitophorus elaeagni, Frankliniella occidentalis P., Dichelops furcatus (F.), Athaumasthus haematicus (Stál), Nezara viridula (L.), Nysius simulans Stál, Edessa meditabunda (F.), Piezodorus guildinii (W.), Helicoverpa zea B., Epicauta adspersa K., Spodoptera frugiperda (J. E. Smith), Chauliognathus scriptus (Germ.), Pantomorus auripes H. and Rachiplusia nu (G.). Regarding aphids, their highest density was observed at the beginning of November, when crop was in the state of branching, with invasion mainly of the upper third of plants: leaves, young shoots and flower heads. Among all harmful true bugs found in the crop, red bug - Athaumastus haematicus (Stál)- comprised the highest proportion and was detected before aphids attacks, when stem elongation of plants was just beginning. As for beneficial species, the six insects detected in sufflower crop were Hippodamia convergens G., Eriopis connexa G., Harmonia axyridis (P.), Nabis sp., Ophion sp. and Apis melifera L., besides various spider species. The coccinellids- Hippodamia convergens; Eriopis connexa and Harmonia axydiris performed as the main natural control agents at crop. KE [ABSTRACT FROM AUTHOR]

Bacterial Infections drug therapy, Bacterial Infections epidemiology, Drug Resistance, Bacterial, Humans, Netherlands epidemiology, Recurrence, Risk Factors, Anti-Bacterial Agents pharmacology, Bacteria drug effects, and Bacterial Infections microbiology

Background: Direct health effects of antibiotic resistance are difficult to assess. We quantified the risk of recurrent bacteremia associated with resistance.
Methods: We extracted antimicrobial susceptibility testing data on blood isolates from the Dutch surveillance system for antimicrobial resistance between 2008 and 2017. First and first recurrent (4-30 days) bacteremia episodes were categorized as susceptible, single nonsusceptible, or co-nonsusceptible to third-generation cephalosporins without or with carbapenems (Enterobacteriaceae), ceftazidime without or with carbapenems (Pseudomonas species), aminopenicillins without or with vancomycin (Enterococcus species), or as methicillin-sensitive/-resistant S. aureus (MSSA/MRSA). We calculated risks of recurrent bacteremia after nonsusceptible vs susceptible first bacteremia, estimated the crude population attributable effect of resistance for the Netherlands, and calculated risks of nonsusceptible recurrent bacteremia after a susceptible first episode.
Results: Risk ratios for recurrent bacteremia after a single- and co-nonsusceptible first episode, respectively, vs susceptible first episode, were 1.7 (95% confidence interval [CI], 1.5-2.0) and 5.2 (95% CI, 2.1-12.4) for Enterobacteriaceae, 1.3 (95% CI, 0.5-3.1) and 5.0 (95% CI, 2.9-8.5) for Pseudomonas species, 1.4 (95% CI, 1.2-1.7) and 1.6 (95% CI, 0.6-4.2) for Enterococcus species, and 1.6 (95% CI, 1.1-2.4) for MRSA vs MSSA. The estimated population annual number of recurrent bacteremias associated with nonsusceptibility was 40. The risk of nonsusceptible recurrent bacteremia after a susceptible first episode was at most 0.4% (Pseudomonas species).
Conclusions: Although antibiotic nonsusceptibility was consistently associated with higher risks of recurrent bacteremia, the estimated annual number of additional recurrent episodes in the Netherlands (40) was rather limited.

Adolescent, Adult, Aged, Aged, 80 and over, Breast Neoplasms mortality, Breast Neoplasms pathology, Breast Neoplasms therapy, Disease-Free Survival, Female, Genotype, Humans, Middle Aged, Mutation, Neoplasm Staging, Prognosis, Proportional Hazards Models, Receptor, ErbB-2 metabolism, Receptors, Estrogen metabolism, Survival Rate, Young Adult, Breast Neoplasms genetics, and Class I Phosphatidylinositol 3-Kinases genetics

Purpose Phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated their prognostic relevance by performing a pooled analysis of individual patient data. Patients and Methods Associations between PIK3CA status and clinicopathologic characteristics were tested by applying Cox regression models adjusted for age, tumor size, nodes, grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, treatment, and study. Invasive disease-free survival (IDFS) was the primary end point; distant disease-free survival (DDFS) and overall survival (OS) were also assessed, overall and by breast cancer subtypes. Results Data from 10,319 patients from 19 studies were included (median OS follow-up, 6.9 years); 1,787 patients (17%) received chemotherapy, 4,036 (39%) received endocrine monotherapy, 3,583 (35%) received both, and 913 (9%) received none or their treatment was unknown. PIK3CA mutations occurred in 32% of patients, with significant associations with ER positivity, increasing age, lower grade, and smaller size (all P < .001). Prevalence of PIK3CA mutations was 18%, 22%, and 37% in the ER-negative/HER2-negative, HER2-positive, and ER-positive/HER2-negative subtypes, respectively. In univariable analysis, PIK3CA mutations were associated with better IDFS (HR, 0.77; 95% CI, 0.71 to 0.84; P < .001), with evidence for a stronger effect in the first years of follow-up (0 to 5 years: HR, 0.73; 95% CI, 0.66 to 0.81; P < .001; 5 to 10 years: HR, 0.82; 95% CI, 0.68 to 0.99; P = .037); > 10 years: (HR, 1.15; 95% CI, 0.84 to 1.58; P = .38; P heterogeneity = .02). In multivariable analysis, PIK3CA genotype remained significant for improved IDFS ( P = .043), but not for the DDFS and OS end points. Conclusion In this large pooled analysis, PIK3CA mutations were significantly associated with a better IDFS, DDFS, and OS, but had a lesser prognostic effect after adjustment for other prognostic factors.

BIODIVERSITY, GRASSHOPPER behavior, BIOMES, PHYLOGENY, and SPECIES distribution

Abstract: The open vegetation biomes, within the limits of the Chacoan subregion, occur along a diagonal in eastern South America covering a large range of environmental conditions. In order to contribute to the knowledge on the biodiversity of these open biomes, we analysed the phylogenetic relationships of the grasshopper genus Zoniopoda to the remaining South American Romaleinae, and examined the biogeographical patterns of diversification of the genus. The study is based on morphological and molecular (COI and H3) evidence, including 12 species of Zoniopoda and 17 species of four tribes of South American Romaleinae. We describe a new species of Zoniopoda, and test its taxonomic placement within the group. Results of our phylogenetic analyses recovered Zoniopoda as a monophyletic group with high support values. According to the dispersion–vicariance analysis, the ancestor of Zoniopoda may have been distributed in an area corresponding to the Chacoan and Cerrado provinces. A vicariant event, that could be explained by the uplift of the Brazilian Plateau and the subsidence of the Chaco, is hypothesized to have occurred splitting the ancestral distribution of Zoniopoda, resulting in the independent evolution of the Tarsata group within the Cerrado and the Iheringi group in the Chacoan subregion. This published work has been registered in ZooBank, http://zoobank.org/urn:lsid:zoobank.org:act:FCFB4C5D-1741-46F1-8E25-B37ED2B9D872. [ABSTRACT FROM AUTHOR]

Biodiversity and Conservation of Natural Resources

MIRIDAE, EGGS as food, PREDATORY animals, TEMPERATURE effect, and MEDITERRANEAN flour moth

Three Neotropical predators Campyloneuropsis infumatus (Carvalho), Engytatus varians (Distant) and Macrolophus basicornis (Stål) (Hemiptera: Miridae) are considered in Brazil as potential biological control agents of Tuta absoluta Meyrick (Lepidoptera: Gelechiidae) and other tomato pests. This study evaluated the effect of five constant temperatures (16, 20, 24, 28 and 32°C, all ±1°C) on the reproduction, population growth and longevity of these predatory mirids. Adults freshly emerged from nymphs reared at each temperature, were separated in couples and kept in 1.7 l glass pots with tobacco plant seedlings (Nicotiana tabacum L., cv. TNN) as oviposition substrate and ad libitum Ephestia kuehniella (Zeller) (Lepidoptera: Pyralidae) eggs as food. The shortest pre-oviposition and the longest oviposition periods were observed at 24°C and 28°C in all three mirid species. At 24°C all three species showed the highest daily and total fecundities. The population growth parameters represented by the intrinsic rate of increase (rm) and the finite rate of increase (λ) were highest at 24°C and 28°C, and the net reproductive rate (R0) was highest at 24°C for all three species. Longevities of both males and females were longest at 24°C and 28°C in all three mirids. The size of tibia and adult weight in the three species were greatest at 20°C and 28°C, respectively. Differences in values for all above variables were small and often statistically non-significant for the three mirid species at the same temperature. Also, not a single significant difference was found for any of the growth parameters at each of the temperatures, including rm. The results indicate that temperatures in the range from 24-28°C are best for reproduction and population growth of C. infumatus, E. varians and M. basicornis. The factitious prey E. kuehniella is an excellent food source and tobacco plants provide a good rearing substrate for these mirids. The obtained results may assist in developing a mass rearing method for C. infumatus, E. varians and M. basicornis, in determining optimal timing and frequency of mirid releases in the crop, and in determining whether they are active at the temperature spectrum observed during tomato production in the field or greenhouse. [ABSTRACT FROM AUTHOR]

Female, Genes, Recessive, Humans, Male, Pregnancy, Congenital Abnormalities genetics, Genetic Diseases, Inborn diagnosis, Parents, Prenatal Diagnosis methods, and Exome Sequencing

Objective: Rare genetic disorders resulting in prenatal or neonatal death are genetically heterogeneous, but testing is often limited by the availability of fetal DNA, leaving couples without a potential prenatal test for future pregnancies. We describe our novel strategy of exome sequencing parental DNA samples to diagnose recessive monogenic disorders in an audit of the first 50 couples referred.
Method: Exome sequencing was carried out in a consecutive series of 50 couples who had 1 or more pregnancies affected with a lethal or prenatal-onset disorder. In all cases, there was insufficient DNA for exome sequencing of the affected fetus. Heterozygous rare variants (MAF < 0.001) in the same gene in both parents were selected for analysis. Likely, disease-causing variants were tested in fetal DNA to confirm co-segregation.
Results: Parental exome analysis identified heterozygous pathogenic (or likely pathogenic) variants in 24 different genes in 26/50 couples (52%). Where 2 or more fetuses were affected, a genetic diagnosis was obtained in 18/29 cases (62%). In most cases, the clinical features were typical of the disorder, but in others, they result from a hypomorphic variant or represent the most severe form of a variable phenotypic spectrum.
Conclusion: We conclude that exome sequencing of parental samples is a powerful strategy with high clinical utility for the genetic diagnosis of lethal or prenatal-onset recessive disorders. © 2017 The Authors Prenatal Diagnosis published by John Wiley & Sons Ltd.
(© 2017 The Authors Prenatal Diagnosis published by John Wiley & Sons Ltd.)

BIODIVERSITY, VERTEBRATES, HABITATS, GLACIATION, and PLIOCENE Epoch

It is now rare to find a semi-aquatic organism group with which to vigorously test whether their diversification model and distribution pattern are closely related to the Cenozoic temperature variation. This hypothesis is explored for water striders of the genera Aquarius Schellenberg, Gerris Fabricius and Limnoporus Stål, which comprise a monophyletic clade with primarily Holarctic distribution. We sample almost 90% of the currently recognized Aquarius, Gerris and Limnoporus species. Five DNA fragments from 62 species are used to reconstruct a phylogram. Divergence time is estimated using Bayesian relaxed-clock method and three fossil calibrations. We investigate diversification dynamics, biogeography and ancestral state reconstruction by using maximum-likelihood, Bayesian and parsimony approaches. Our results showed that the crown of the three genera originated and underwent an initial diversification in Asia at 72 Ma (HPD: 59-86 Ma) in the Late Cretaceous, subsequently expanding into other regions via dispersal. The Bering Land Bridge was the major migration route between Eurasia and North America but was interrupted before the early Oligocene (34 Ma). Ancestors most likely used lentic habitats, and a minimum of two independent shifts to lotic habitats occurred in the initial diversification. Cenozoic temperature variation regulated the evolutionary history of Holarctic water striders of the genera Aquarius, Gerris and Limnoporus. Temperature warming during Stage I (52-66 Ma) was associated with the disappearance of shallow lentic habitats; this phenomenon forced certain lentic lineages to colonize new lotic habitats and promoted the diversification of lineages. Temperature cooling during Stage II (after 34 Ma) was associated with the fragmentation of water habitats of the 'mixed-mesophytic' belt, resulting in the extinction of historical taxa and influencing close lineages that shaped the present disjunct Eurasian-North American distribution. [ABSTRACT FROM AUTHOR]

ZOOLOGICAL nomenclature, LEAFHOPPERS, PARROTFISHES, BURSA fabricii, and ANNOTATIONS

A synoptic, annotated catalogue is provided, documenting the long history of vacillated nomenclature usages between leafhopper family-group names Gyponidae Stål 1870c and Scaridae Amyot & Serville 1843a (nec Scaridae Rafinesque 1810b), between genus-group names Gypona Germar 1821a and Scaris Le Peletier & Serville 1828a (nec Scaris Chaudoir 1879), synonyms, and use of Docalidia ferruginea (Fabricius) in the literature for Iassus ferrugineus, beginning at the formation of each taxon and ending at the present. Authors' annotations, where applicable, follow each citation. A photograph of the lectotype of Iassus ferrugineus Fabricius (Coelidiinae) and a misidentified specimen (Gyponinae) by Germar are shown for comparative purposes. [ABSTRACT FROM AUTHOR]

HEMIPTERA, STINKBUGS, INSECT behavior, BROWN marmorated stink bug, and INSECT traps

Light trapping is a common method for monitoring and capturing insects such as the invasive agricultural pest, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae). Efforts to develop more effective trapping methods for H. halys have led to research investigating the response of this insect to potentially exploitable stimuli. A behavioral study was conducted to examine the response of H. halys to various light stimuli. Seven intensities (0 [control: dark], 0.1, 10, 50, 75, 100, and 155 lx) of white light were tested. The most attractive intensity for H. halys was 75 lx for adult males and females. Nymphal instars 2 to 5, adult males, and adult females were also exposed to 75 lx white light. Adult males were significantly more attracted to the light than any other life stage. Adults were also exposed to green, orange, red, white, and yellow light. All colors tested were attractive to H. halys. White light was significantly more attractive than the other tested colors. The findings of this study suggest that the incorporation of a white light into H. halys traps may increase the number captured. [ABSTRACT FROM AUTHOR]

ARTHROPODA, ARBOREAL animals, SALTCEDAR, and LARVAE

Although biological control agents are imported without the constraints exerted by their native natural enemies, many native, generalist arthropod predators might use the new food source after release in the field. Predation by native arthropods is a potential obstacle to establishment of Diorhabda spp. as a biological control agent against saltcedar, Tamarix spp. Arboreal predaceous insects were surveyed at the Great Salt Plains National Wildlife Refuge to identify possible predators that could affect establishment of the northern tamarisk beetle, Diorhabda carinulata (Desbrochers), in Oklahoma. Results of the survey showed that 57% of the arthropods were represented by five insects, Zelus tetracanthus (Stål) (Hemiptera: Reduviidae) (21%); several species of Chrysoperla (Neuroptera: Chrysopidae) (11%); the insidious flower bug, Orius insidiosus (Say) (Hemiptera: Anthocoridae) (10%); Collops quadrimaculatus (F.) Coleoptera: Melydridae) (8%); and the sevenspotted lady beetle, Coccinella septempunctata L. (Coleoptera: Coccinellidae) (6%), in saltcedar stands. No-choice feeding studies demonstrated that eggs and larvae of D. carinulata were accepted prey for larvae of Chrysoperla rufilabris (Burmeister) and sevenspotted lady beetle adults but not larvae. Northern tamarisk beetle larvae were accepted prey for Z. tetracanthus. [ABSTRACT FROM AUTHOR]

Animals, Housing, Seasons, Chemotaxis, Heteroptera physiology, Insect Control, and Pheromones pharmacology

The brown marmorated stink bug, Halyomorpha halys (Stål), is an invasive species from Asia capable of causing severe agricultural damage. It can also be a nuisance pest when it enters and exits anthropogenic overwintering sites. In recent years, pheromone lures and traps for H. halys have been developed and used to monitor populations in field studies. To date, no study has investigated the applicability of these monitoring tools for use indoors by building residents during the overwintering period. Herein, we 1) assessed when in late winter (diapause) and spring (postdiapause) H. halys begins to respond to its pheromone (10,11-epoxy-1-bisabolen-3-ol), 2) evaluated whether pheromone-based tools can be used reliably for monitoring H. halys adults in unheated and heated buildings, and 3) elucidated the potential for indoor management using pheromone-baited traps. A 2-yr trapping study suggested that H. halys began to respond reliably to pheromone-baited traps after a critical photoperiod of 13.5 h in the spring. Captures before that point were not correlated with visual counts of bugs in buildings despite robust populations, suggesting currently available pheromone-baited traps were ineffective for surveillance of diapausing H. halys. Finally, because baited traps captured only 8-20% of the adult H. halys known to be present per location, they were not an effective indoor management tool for overwintering H. halys. Our study contributes important knowledge about the capacity of H. halys to perceive its pheromone during overwintering, and the ramifications thereof for building residents with nuisance problems.
(Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by US Government employees and is in the public domain in the US.)

BROWN marmorated stink bug, HEMIPTERA, INTRODUCED insects, INSECT pests, PHEROMONES, INSECT traps, INSECT population density, and ECONOMICS

Halyomorpha halys Stål (Hemiptera: Pentatomidae) is an invasive insect that causes severe economic damage to multiple agricultural commodities. Several monitoring tools, including pheromone and light-baited black pyramid traps, have been developed to monitor H. halys. Here, we evaluated the attractiveness of these traps baited with only light, only pheromone, or the combination in comparison with unbaited traps throughout the growing season in regions with high and low H. halys population densities. In regions with high population densities in the Mid-Atlantic, all traps baited with pheromone or lights performed better than control traps. During mid-season, traps containing lights captured more H. halys adults, whereas pheromone-baited traps captured greater numbers during the late season. In low density regions in the Pacific Northwest, traps with lights or pheromone captured more H. halys adults than control traps. In addition, we evaluated the influence of competing light sources associated with anthropogenic structures. When light traps were deployed next to these additional light sources, H. halys captures in pyramid traps baited with light were not significantly reduced. Overall, our results indicate that both light and pheromone traps can be used to detect H. halys activity in low and high density populations. [ABSTRACT FROM AUTHOR]

HIGGS bosons, SCALAR field theory, SUPERSYMMETRY, STANDARD model (Nuclear physics), DARK matter, and MATHEMATICAL models

The goal of this report is to summarize the current situation and discuss possible search strategies for charged scalars, in non-supersymmetric extensions of the Standard Model at the LHC. Such scalars appear in Multi-Higgs-Doublet models, in particular in the popular Two-Higgs-Doublet model, allowing for charged and additional neutral Higgs bosons. These models have the attractive property that electroweak precision observables are automatically in agreement with the Standard Model at the tree level. For the most popular version of this framework, Model II, a discovery of a charged Higgs boson remains challenging, since the parameter space is becoming very constrained, and the QCD background is very high. We also briefly comment on models with dark matter which constrain the corresponding charged scalars that occur in these models. The stakes of a possible discovery of an extended scalar sector are very high, and these searches should be pursued in all conceivable channels, at the LHC and at future colliders. [ABSTRACT FROM AUTHOR]

NEISSERIA gonorrhoeae, SEXUALLY transmitted diseases, ANTIBIOTICS, CHLAMYDIA trachomatis, GYNECOLOGISTS, DIAGNOSIS, CHLAMYDIA infection diagnosis, GENITOURINARY disease diagnosis, GONORRHEA diagnosis, CLINICS, GENITOURINARY diseases, GONORRHEA, DISEASES in men, NEISSERIA, PHARYNGEAL diseases, PHYSICIANS, GENERAL practitioners, CROSS-sectional method, and RECTAL diseases

Background: Gonorrhoea, caused by Neisseria gonorrhoeae (NG), can cause reproductive morbidity, is increasingly becoming resistant to antibiotics and is frequently asymptomatic, which shows the essential role of NG test practice. In this study we wanted to compare NG diagnostic testing procedures between different STI care providers serving a defined geographic Dutch region (280,000 inhabitants).Methods: Data on laboratory testing and diagnosis of urogenital and extragenital (i.e. anorectal and oropharyngeal) NG were retrieved from general practitioners (GPs), an STI clinic, and gynaecologists (2006-2010). Per provider, we assessed their contribution regarding the total number of tests performed and type of populations tested, the proportion of NG positives re-tested (3-12 months after treatment) and test-of-cure (TOC, within 3 months post treatment).Results: Overall, 17,702 NG tests (48.7% STI clinic, 38.2% GPs, 13.1% gynaecologists) were performed during 15,458 patient visits. From this total number of tests, 2257 (12.7%) were extragenital, of which 99.4% were performed by the STI clinic. Men were mostly tested at the STI clinic (71%) and women by their GP (43%). NG positivity per visit was 1.6%; GP 1.9% (n = 111), STI clinic 1.7% (n = 131) and gynaecology 0.2% (n = 5). NG positivity was associated with Chlamydia trachomatis positivity (OR: 2.06, 95% confidence interval: 1.46-2.92). Per anatomical location, the proportion of NG positives re-tested were: urogenital 20.3% (n = 36), anorectal 43.6% (n = 17) and oropharyngeal 57.1% (n = 20). NG positivity among re-tests was 16.9%. Proportions of NG positives with TOC by anatomical location were: urogenital 10.2% (n = 18), anorectal 17.9% (n = 7) and oropharyngeal 17.1% (n = 6).Conclusions: To achieve best practice in relation to NG testing, we recommend that: 1) GPs test at extragenital sites, especially men who have sex with men (MSM), 2) all care providers consider re-testing 3 to 12 months after NG diagnosis and 3) TOC is performed following oropharyngeal NG diagnosis in settings which provide services to higher-risk men and women (such as STI clinics). [ABSTRACT FROM AUTHOR]

PHYLOGENY, MORPHOGENESIS, EVOLUTIONARY developmental biology, ORGANISMS, MICROBIAL ecology, and TAXONOMY

Robust phylogenetic hypotheses have become key for studies addressing the evolutionary biology and ecology of various groups of organisms. In the species-rich heteropteran superfamily Pentatomoidea, phylogenies at lower taxonomic levels are still scarce and mostly employ exclusively morphological data. In this study, we conducted a total evidence phylogeny focusing on the tribe Carpocorini (Pentatomidae), using morphological data and four DNA markers ( COI, Cytb, 16S and 28S rDNA; ∼2330 bp; 32 taxa) in order to investigate the relationships within Euschistus Dallas, one of the most speciose pentatomid genera, and between Euschistus and related genera. Our hypotheses generated by maximum likelihood and Bayesian inference show that the current taxonomic composition and classification of Euschistus and allied genera are in need of revision. Euschistus was recovered as nonmonophyletic, with the subgenera forming four independent lineages: Euschistus ( Euschistus) and Euschistus ( Lycipta) Stål are sister groups; Euschistus ( Euschistomorphus) Jensen-Haarup is more closely related to Dichelops Spinola and Agroecus Dallas; and Mitripus Rolston is divided into two clades closely related to Sibaria Stål and Ladeaschistus Rolston. We chose not to change the classification of E. ( Euschistomorphus) until further data become available, and propose to split Euschistus into three genera with the exclusion of Euschistus ( Mitripus) and all of its species. Here we elevate Mitripus to genus rank to include M. acutus comb.n., M. convergens comb.n. and M. legionarius comb.n., and propose Adustonotus Bianchi gen.n. to include A. anticus comb.n., A. latus comb.n., A. tauricornis comb.n., A. grandis comb.n., A. hansi comb.n., A. paranticus comb.n., A. irroratus comb.n. and A. saramagoi comb.n. We also provide identification keys to the genera Adustonotus gen.n., Ladeaschistus, Mitripus n. rank and Sibaria, here defined as the Mitripus genus group, and to the species of Mitripus and Adustonotus gen.n. Our results provide insights into the current status of the classification of the Pentatomidae, suggesting the need for phylogenetic analyses at different taxonomic levels within stink bugs. This published work has been registered in ZooBank, . [ABSTRACT FROM AUTHOR]

HEMIPTERA and STINKBUGS

The Neotropical genus Lincus Stål, 1867 is frequently associated with the transmission of diseases to palms and coconut trees (Elaeis guineensis and Cocos nucifera) in commercial plantations in South America. Here we update the geographical distribution of 15 species of Lincus collected in E. guineensis and C. nucifera in the Neotropics. The geographical range of five species is expanded with new countries recorded for L. malevolus and L. styliger, and detailed geographic information is given for the first time for L. lobuliger and L. securiger. [ABSTRACT FROM AUTHOR]

DOUBLE-stranded RNA, SAP (Plant), INSECT-plant relationships, INSECT pests, and GENE silencing

Double-stranded RNA (dsRNA)-mediated gene silencing, also known as RNA interference (RNAi), has been a breakthrough technology for functional genomic studies and represents a potential tool for the management of insect pests. Since the inception of RNAi numerous studies documented successful introduction of exogenously synthesized dsRNA or siRNA into an organism triggering highly efficient gene silencing through the degradation of endogenous RNA homologous to the presented siRNA. Managing hemipteran insect pests, especially Halyomorpha halys (Stål) (Heteroptera: Pentatomidae), the brown marmorated stink bug (BMSB), is critical to food productivity. BMSB was recently introduced into North America where it is both an invasive agricultural pest of high value specialty, row, and staple crops, as well as an indoor nuisance pest. RNAi technology may serve as a viable tool to manage this voracious pest, but delivery of dsRNA to piercing-sucking insects has posed a tremendous challenge. Effective and practical use of RNAi as molecular biopesticides for biocontrol of insects like BMSB in the environment requires that dsRNAs be delivered in vivo through ingestion. Therefore, the key challenge for molecular biologists in developing insect-specific molecular biopesticides is to find effective and reliable methods for practical delivery of stable dsRNAs such as through oral ingestion. Here demonstrated is a reliable delivery system of effective insect-specific dsRNAs through oral feeding through a new delivery system to induce a significant decrease in expression of targeted genes such as JHAMT and Vg. This state-of-the-art delivery method overcomes environmental delivery challenges so that RNAi is induced through insect-specific dsRNAs orally delivered to hemipteran and other insect pests. [ABSTRACT FROM AUTHOR]

Adult, Aged, Biomarkers blood, Fatty Acids blood, Female, Fibrosis, Glycerophospholipids blood, Humans, Liver pathology, Liver Cirrhosis etiology, Logistic Models, Male, Middle Aged, Multivariate Analysis, Prospective Studies, Risk Factors, Severity of Illness Index, Surveys and Questionnaires, Sweden, Young Adult, Alcohol Drinking, Liver Cirrhosis pathology, Non-alcoholic Fatty Liver Disease complications, and Non-alcoholic Fatty Liver Disease pathology

Background and Aim: Moderate alcohol consumption has been associated with a lower risk of disease severity in non-alcoholic fatty liver disease (NAFLD). It is unclear if this reflects current or lifetime drinking, or can be attributed to confounders such as diet and exercise. We evaluated the impact of lifetime alcohol consumption on fibrosis severity in NAFLD.
Methods: We prospectively enrolled 120 subjects with biopsy-proven NAFLD and through detailed questionnaires examined lifetime alcohol consumption, diet and physical activity. Main outcome measures were odds ratios (OR) for fibrosis stage, calculated through ordinal regression after adjustment for body mass index, diabetes mellitus type 2, smoking and age at biopsy. A biomarker for recent alcohol consumption, phosphatidyl ethanol (PEth) was sampled.
Results: An increase in median weekly alcohol consumption to a maximum of 13 drinks per week was associated with lower fibrosis stage (adjusted OR for each incremental unit, 0.86; 95% CI, 0.76-0.97; p = .017). The lowest risk for fibrosis was found with the lowes`t odds seen in the top quartile of alcohol consumption (aOR 0.23; 95% CI 0.08-0.66; p = .006). Adding soft drink and coffee consumptions, and physical activity to the model did not change the estimates. Subjects with PEth ≥0.3 μmol/L had higher ORs for a higher fibrosis stage (aOR 2.77; 95% CI 1.01-7.59; p = .047).
Conclusion: Lifetime alcohol consumption with up to 13 units per week is associated with lower fibrosis stage in NAFLD. Elevated PEth is associated with higher stages of fibrosis.

Adult, Aged, Aged, 80 and over, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Cohort Studies, Female, Follow-Up Studies, Humans, Immunoenzyme Techniques, Lymphatic Metastasis, Middle Aged, Neoplasm Grading, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local metabolism, Neoplasm Staging, Prognosis, Receptor, ErbB-2 metabolism, Receptors, Estrogen metabolism, Receptors, Progesterone metabolism, Survival Rate, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor metabolism, Breast Neoplasms classification, Breast Neoplasms pathology, and Neoplasm Recurrence, Local pathology

Background: The St Gallen surrogate definition of the intrinsic subtypes of breast cancer consist of five subgroups based on estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor type 2 (HER2), and Ki-67. PgR and Ki-67 are used for discriminating between the 'Luminal A-like' and 'Luminal B-like (HER2-negative)' subtypes. Histological grade (G) has prognostic value in breast cancer; however, its relationship to the St Gallen subtypes is not clear. Based on a previous pilot study, we hypothesized that G could be a primary discriminator for ER-positive/HER2-negative breast cancers that were G1 or G3, whereas Ki-67 and PgR could provide additional prognostic information specifically for patients with G2 tumors. To test this hypothesis, a larger patient cohort was examined.
Patients and Methods: Six hundred seventy-one patients (≥35 years of age, pT1-2, pN0-1) with ER-positive/HER2-negative breast cancer and complete data for PgR, Ki-67, G, lymph node status, tumor size, age, and distant disease-free survival (DDFS; median follow-up 9.2 years) were included.
Results: 'Luminal A-like' tumors were mostly G1 or G2 (90%) whereas 'Luminal B-like' tumors were mostly G2 or G3 (87%) and corresponded with good and poor DDFS, respectively. In 'Luminal B-like' tumors that were G1 (n = 23), no metastasis occurred, whereas 14 of 40 'Luminal A-like' tumors that were G3 metastasized. In the G2 subgroup, low PgR and high Ki-67 were associated with an increased risk of distant metastases, hazard ratio (HR) and 95% confidence interval (CI) 1.8 (0.95-3.4) and 1.5 (0.80-2.8), respectively.
Conclusions: Patients with ER-positive/HER2-negative/G1 breast cancer have a good prognosis, similar to that of 'Luminal A-like', while those with ER-positive/HER2-negative/G3 breast cancer have a worse prognosis, similar to that of 'Luminal B-like', when assessed independently of PgR and Ki-67. Therapy decisions based on Ki-67 and PgR might thus be restricted to the subgroup G2.

RICE diseases & pests, NILAPARVATA lugens, LOCUS (Genetics), GENETIC markers in plants, and RICE breeding

Brown planthopper ( BPH), Nilaparvata lugens Stål ( Hemiptera: Delphacide), is a destructive insect pest of rice, Oryza sativa L. ( Poaceae), in rice-producing areas worldwide. Host plant resistance is a major aspect of managing this pest. In this study, a mapping population consisting of 150 F3 lines, derived from a cross of MR276 and Rathu Heenati, was used to detect and analyse quantitative trait loci ( QTLs) for the resistance to BPH. Composite Interval Mapping ( CIM) was used for QTL detection. In total 10 QTLs controlling BPH resistance were mapped on chromosomes 1, 3, 6, 7, 9, 10, and 12. Four QTLs - qBph-1-1, qBph-3-1, qBph-6-1, and qBph-7-1 - were mapped on chromosomes 1, 3, 6, and 7 in the standard seedbox screening test, explaining 41% of the phenotypic variance. Two QTLs, qBph-6-1 and qBph-9-1, were detected on chromosomes 6 and 9 in the honeydew test, accounting for 32% of the total phenotypic variance. Moreover, four QTLs - qBph-3-1, qBph-6-1, qBph-10-1, and qBph-12-1 - were identified on chromosomes 3, 6, 10, and 12 expressing antixenosis to BPH and explaining 41% of the phenotypic variance. QTL qBph-3-1 was located in the chromosomal region between markers RM231 and RM3872 on chromosome 3, and QTL qBph-6-1 was located in the region between RM588 and RM204 on chromosome 6, indicating that these regions have a major effect in controlling the resistance to BPH in the population studied. The molecular markers linked to QTLs that are identified will be useful in the development of varieties resistant to BPH. Our study contributes to the development of genetic material for breeding programmes and marker-assisted selection ( MAS) in rice to improve BPH resistance. [ABSTRACT FROM AUTHOR]

A crude rice extract caused a higher probing response than did the control in the green rice leafhopper, Nephotettix nigropictus . Bioassay-guided separation led to the isolation of four active compounds, isoscoparin 2″- O -glucoside, isoscoparin 2″- O -(6‴-( E )-feruloyl)glucoside, isoscoparin 2″- O -(6‴-( E )- p -coumaroyl)glucoside, and isovitexin 2″- O -(6‴-( E )-feruloyl)glucoside from ODS 40% methanol in water faction. Each of the compounds, or any combination without one of the four compounds, caused weaker probing responses than the crude rice extract. The activity was recovered only when all the compounds were combined.

BROWN marmorated stink bug, AGRICULTURAL ecology, POPULATION dynamics, PHYSIOLOGICAL control systems, and PARASITISM

Understanding native natural enemy impacts on the invasive brown marmorated stink bug, Halyomorpha halys (Stål), offers insight into the population dynamics of this invasive pest and the potential for biological control. This two-year study offers a broad-scale assessment of mortality factors affecting sentinel and naturally laid H. halys eggs in agroecosystems in the pest’s invaded range in eastern North America. Predation and parasitism rates varied among states and crops, but overall were low. Average maximum levels of biological control were estimated to be about 19% and 20% in 2013 and 2014, respectively. Of the eggs destroyed by natural enemies, chewing predation was the most prevalent. Parasitism by native parasitoids was very low, with adult parasitoids emerging from <1% of eggs averaged across crops, locations, and years; an additional 2.8% of eggs contained partially developed parasitoids. Lower percentages of sentinel H. halys hatched in organically versus conventionally managed crops, and in most cases had higher percentages of predation. Parasitism of sentinel and naturally laid eggs of the native stink bugs Euschistus servus (Say) and Chinavia hilare (Say) averaged 49.3% (±8.6 SE) and 0.6% (±0.3), respectively, across locations and years. Telenomus podisi (Ashmead) was the most common parasitoid parasitizing E. servus and H. halys eggs, but rarely did >1 individual parasitoid emerge from a H. halys egg mass. Parasitism of H. halys eggs by a complex of parasitoids is an important population regulation factor in its native Asian range, but this study found that parasitoids native to eastern US agroecosystems do not provide that service in this introduced region. The greatest potential for biological control of H. halys may be via classical biological control by the Asian parasitoid Trissolcus japonicus (Ashmead), which has recently been detected in both the eastern and western US. [ABSTRACT FROM AUTHOR]

STIMULANTS, LEAFHOPPERS, RICE diseases & pests, BIOLOGICAL assay, and METHANOL

A crude rice extract caused a higher probing response than did the control in the green rice leafhopper, Nephotettix nigropictus. Bioassay-guided separation led to the isolation of four active compounds, isoscoparin 2"-O-glucoside, isoscoparin 2"-O-(6"'-(E)-feruloyl)glucoside, isoscoparin 2"-O-(6"'-(E)-p-coumaroyl)glucoside, and isovitexin 2"-O-(6"'- (E)-feruloyl)glucoside from ODS 40% methanol in water faction. Each of the compounds, or any combination without one of the four compounds, caused weaker probing responses than the crude rice extract. The activity was recovered only when all the compounds were combined. [ABSTRACT FROM AUTHOR]

NONFICTION

Books reviewed in this issue L iterature and F ine A rts Martinsen, Deborah A., and Olga Maiorova, eds. Dostoevsky in Context. Marullo, Thomas Gaiton. Heroine Abuse: Dostoevsky's Netochka Nezvanova and the Poetics of Codependency. Salmond, Wendy, Wilfried Zeisler, and Russell E. Martin. Konstantin Makovsky: The Tsar's Painter in America and Paris. Gregory, Serge. Antosha and Levitasha: The Shared Lives and Art of Anton Chekhov and Isaac Levitan. Pickford, Henry W. Thinking with Tolstoy and Wittgenstein: Expression, Emotion, and Art. Wunsche, Isabel. The Organic School of the Russian Avant-Garde: Nature's Creative Principles. Weld, Sara Pankenier. Voiceless Vanguard: The Infantilist Aesthetic of the Russian Avant-Garde. Mitchell, Rebecca. Nietzsche's Orphans: Music, Metaphysics, and the Twilight of the Russian Empire. Bartlett, Rosamund, and Sarah Dadswell, eds. and trans. Victory over the Sun: The World's First Futurist Opera. Kukulin, Il'ia. Mashiny zashumevshego vremeni: Kak sovetskii montazh stal metodom neofitsial'noi kul'tury. Van Buskirk, Emily. Lydia Ginzburg's Prose: Reality in Search of Literature. Garipova, Nailya, and Juan José Torres Núñez, eds. Women in Nabokov's Life and Art. Blackwell, Stephen H., and Kurt Johnson, eds. Fine Lines: Vladimir Nabokov's Scientific Art. Skomp, Elizabeth A., and Benjamin M. Sutcliffe. Ludmila Ulitskaya and the Art of Tolerance. Cederlöf, Henriette. Alien Places in Late Soviet Science Fiction: The 'Unexpected Encounters' of Arkady and Boris Strugatsky as Novels and Films. Anderson, Richard. Russia. H istory Barnes, Ian. Restless Empire: A Historical Atlas of Russia. Soroka, Marina, and Charles A. Ruud. Becoming a Romanov: Grand Duchess Elena of Russia and Her World (1807-1873). Suny, Ronald Grigor. ' They Can Live in the Desert but Nowhere Else': A History of the Armenian Genocide. Siegel, Jennifer. For Peace and Money: French and British Finance in the Service of Tsars and Commissars. Stoff, Laurie S. Russia's Sisters of Mercy and the Great War: More than Binding Men's Wounds. Smele, Jonathan D. The 'Russian' Civil Wars, 1916-1926: Ten Years That Shook the World. Dornik, Wolfram, et al., eds. The Emergence of Ukraine: Self-Determination, Occupation, and War in Ukraine, 1917-1922. Khalid, Adeeb. Making Uzbekistan: Nation, Empire, and Revolution in the Early USSR. Graham, Loren. Lysenko's Ghost: Epigenetics and Russia. Levin, Zeev. Collectivization and Social Engineering: Soviet Administration and the Jews of Uzbekistan, 1917-1939. Jordan, Pamela A. Stalin's Singing Spy: The Life and Exile of Nadezhda Plevitskaya. Whitewood, Peter. The Red Army and the Great Terror: Stalin's Purge of the Soviet Military. Horowitz, Brian, and Leonid Katsis, eds. Vladimir Jabotinsky's Story of My Life. Ellis, Frank. Barbarossa 1941. Harrison, Richard W. ed. and trans. Rollback: The Red Army's Winter Offensive along the Southwestern Strategic Direction, 1942-1943. Harrison, Richard W. ed. and trans. Prelude to Berlin: The Red Army's Offensive Operations in Poland and Eastern Germany, 1945. Fitzpatrick, Sheila. On Stalin's Team: The Years of Living Dangerously in Soviet Politics. Karlsson, Klas-Göran, Johan Stenfeldt, and Ulf Zander, eds. Perspectives on the Entangled History of Communism and Nazism: A Comnaz Analysis. Varga-Harris, Christine. Stories of House and Home: Soviet Apartment Life during the Khrushchev Years. Friedman, Jeremy. Shadow Cold War: The Sino-Soviet Competition for the Third World. Lesourd, Françoise, ed. Les mutations religieuses en Russie: Conversions et sécularisation. Haslam, Jonathan. Near and Distant Neighbors: A New History of Soviet Intelligence. Pipes, Richard. Alexander Yakovlev: The Man Whose Ideas Delivered Russia from Communism. Weeks, Theodore R. Vilnius between Nations, 1795-2000. Luehrmann, Sonja. Religion in Secular Archives: Soviet Atheism and Historical Knowledge. Brumfield, William Craft. Architecture at the End of the Earth: Photographing the Russian North. S ocial S ciences, C ontemporary R ussia, and O ther Rogers, Douglas. The Depths of Russia: Oil, Power, and Culture after Socialism. Hedlund, Stefan. Putin's Energy Agenda: The Contradictions of Russia's Resource Wealth. Nalbandov, Robert. Not by Bread Alone: Russian Foreign Policy under Putin. Pacer, Valerie A. Russian Foreign Policy under Dmitry Medvedev, 2008-2012. Prina, Federica. National Minorities in Putin's Russia: Diversity and Assimilation. Soldatov, Andrei, and Irina Borogan. The Red Web: The Struggle between Russia's Digital Dictators and the New Online Revolutionaries. Stanislav, Markus. Property, Predation and Protection: Piranha Capitalism in Russia and Ukraine. White, Stephen, and Valentina Feklyunina. Identities and Foreign Policies in Russia, Ukraine and Belarus: The Other Europes. [ABSTRACT FROM AUTHOR]

Adenoma genetics, Adolescent, Adult, Female, Gene Frequency, Growth Hormone-Secreting Pituitary Adenoma genetics, Humans, Male, Mexico, Mutation, Young Adult, Acromegaly genetics, Gigantism genetics, and Intracellular Signaling Peptides and Proteins genetics

Although aryl hydrocarbon receptor-interacting protein (AIP) mutations are rare in sporadic acromegaly, their prevalence among young patients is nonnegligible. The objectives of this study were to evaluate the frequency of AIP mutations in a cohort of Mexican patients with acromegaly with disease onset before the age of 30 and to search for molecular abnormalities in the AIP gene in teeth obtained from the "Tampico Giant". Peripheral blood DNA from 71 patients with acromegaly (51 females) with disease onset <30 years was analysed (median age of disease onset of 23 years) and correlated with clinical, biochemical and imaging characteristics. Sequencing was also carried out in DNA extracted from teeth of the Tampico Giant. Five patients (7 %) harboured heterozygous, germline mutations of the AIP gene. In two of them (a 9-year-old girl with gigantism and a young man with symptoms of GH excess since age 14) the c.910C>T (p.Arg304Ter), well-known truncating mutation was identified; in one of these two cases and her identical twin sister, the mutation proved to be a de novo event, since neither of their parents were found to be carriers. In the remaining three patients, new mutations were identified: a frameshift mutation (c.976_977insC, p.Gly326AfsTer), an in-frame deletion (c.872_877del, p.Val291_Leu292del) and a nonsense mutation (c.868A > T, p.Lys290Ter), which are predicted to be pathogenic based on in silico analysis. Patients with AIP mutations tended to have an earlier onset of acromegaly and harboured larger and more invasive tumours. A previously described genetic variant of unknown significance (c.869C > T, p.Ala299Val) was identified in DNA from the Tampico Giant. The prevalence of AIP mutations in young Mexican patients with acromegaly is similar to that of European cohorts. Our results support the need for genetic evaluation of patients with early onset acromegaly.

Tuta absoluta (Meyrick) has quickly developed into a significant tomato pest worldwide. While the recently found mirid predators Macrolophus basicornis (Stal), Engytatus varians (Distant) and Campyloneuropsis infumatus (Carvalho) of this pest are able to establish and reproduce on tomato, biological knowledge of these mirids is still limited. Here we describe the functional response of the three mirid predators of the tomato pest T. absoluta when offered a range of prey densities (four, eight, 16, 32, 64, 128 and 256 eggs) during a 24 h period inside cylindrical plastic cages in the laboratory. Engytatus varians and M. basicornis showed a type III functional response, whereas C. infumatus showed a type II functional response. At the highest prey densities, C. infumatus consumed an average of 51.0 eggs, E. varians 91.1 eggs, and M. basicornis 100.8 eggs. Taking all information into account that we have collected of these three Neotropical mirid species, we predict that M. basicornis might be the best candidate for control of the tomato borer in Brazil: it has the highest fecundity, the largest maximum predation capacity, and it reacts in a density-dependent way to the widest prey range.
Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

PARASITOIDS, BROWN marmorated stink bug, PLANT parasites, INTRODUCED insects, LADYBUGS, STINKBUGS, and SPECIES distribution

Halyomorpha halys is an invasive species, originating from East Asia, which was accidentally introduced in some areas of North America and Europe, where severe damages to different vegetable crops and fruit plants were recorded. Several studies in different countries focused on the possibility to apply biological control by means of eggparasitoids. The main egg-parasitoids in the original area are unfortunately non-specific and thus the application of classical biological control is questionable. On the other hand, the possibility of using augmentative biological control by native egg-parasitoids able to exploit the new host is an interesting possibility in both Europe and the USA. In a preliminary assay, frozen egg masses of H. halys were exposed in the field in Central Italy. Results showed that some eggs were exploited by parasitoids belonging to the species Anastatus bifasciatus and Ooencyrtus telenomicida. Therefore, different native egg-parasitoids species widespread in Europe were tested in the laboratory in order to explore their ability to parasitize H. halys eggs. To this end, no-choice tests were carried out in climatic chambers (26°C, 70%RH, 16:8 L:D) in order to evaluate the parasitization potential of females collected in the wild. Conducted tests pointed out that A. bifasciatus and especially O. telenomicida may be potential candidates for the biological control of H. halys. In particular, O. telenomicida was able to parasitize the 35.56% of the exposed host eggs in the lab tests. New adults successfully emerged from the 22.92% of the eggs, and on the whole, this egg-parasitoid caused a significant hatching reduction of the H. halys eggs (more than 70%). Conversely, Telenomus chloropus and Ooencyrtus pityocampae were less promising species as biocontrol agents of this agricultural pest. Preliminary trials in pear orchards consisting of field releases of laboratory-reared specimens of O. telenomicida, one of the potential candidates for biological control, showed that this parasitoid is actually able to discover egg masses of H. halys (sentinel frozen egg masses) and to successfully parasitize them. [ABSTRACT FROM AUTHOR]

Adenoma genetics, Adenoma pathology, Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Genetic Testing, Germ-Line Mutation, Growth Hormone-Secreting Pituitary Adenoma genetics, Growth Hormone-Secreting Pituitary Adenoma pathology, Humans, Longitudinal Studies, Male, Middle Aged, Mutation, Pituitary Neoplasms genetics, Pituitary Neoplasms pathology, Prospective Studies, Young Adult, Adenoma diagnosis, Growth Hormone-Secreting Pituitary Adenoma diagnosis, Intracellular Signaling Peptides and Proteins genetics, and Pituitary Neoplasms diagnosis

Context: Familial isolated pituitary adenoma (FIPA) due to aryl hydrocarbon receptor interacting protein (AIP) gene mutations is an autosomal dominant disease with incomplete penetrance. Clinical screening of apparently unaffected AIP mutation (AIPmut) carriers could identify previously unrecognized disease.
Objective: To determine the AIP mutational status of FIPA and young pituitary adenoma patients, analyzing their clinical characteristics, and to perform clinical screening of apparently unaffected AIPmut carrier family members.
Design: This was an observational, longitudinal study conducted over 7 years.
Setting: International collaborative study conducted at referral centers for pituitary diseases.
Participants: FIPA families (n 216) and sporadic young-onset (30 y) pituitary adenoma patients (n 404) participated in the study.
Interventions: We performed genetic screening of patients for AIPmuts, clinical assessment of their family members, and genetic screening for somatic GNAS1 mutations and the germline FGFR4 p.G388R variant.
Main Outcome Measure(s): We assessed clinical disease in mutation carriers, comparison of characteristics of AIPmut positive and negative patients, results of GNAS1, and FGFR4 analysis.
Results: Thirty-seven FIPA families and 34 sporadic patients had AIPmuts. Patients with truncating AIPmuts had a younger age at disease onset and diagnosis, compared with patients with nontruncating AIPmuts. Somatic GNAS1 mutations were absent in tumors from AIPmut-positive patients, and the studied FGFR4 variant did not modify the disease behavior or penetrance in AIPmut-positive individuals. A total of 164 AIPmut-positive unaffected family members were identified; pituitary disease was detected in 18 of those who underwent clinical screening.
Conclusions: A quarter of the AIPmut carriers screened were diagnosed with pituitary disease, justifying this screening and suggesting a variable clinical course for AIPmut-positive pituitary adenomas.

LANTANA camara, ORNAMENTAL plants, BIOSAFETY, QUARANTINE, ECOSYSTEM dynamics, NATURALIZATION, and WEEDS

The article presents a research focused on analyzing the status of ornamental plant lantana camara that grows in the urban areas and also discusses its implication on the biosafety and quarantine of the region. Various topics discussed in the research includes natural enemies of lantana, natural ecosystem of Botswana and impact of naturalization on weed removal.

Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Confidence Intervals, Disease-Free Survival, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Liver Neoplasms mortality, Liver Neoplasms pathology, Male, Middle Aged, Niacinamide therapeutic use, Patient Selection, Proportional Hazards Models, Remission Induction, Sorafenib, Survival Analysis, Time Factors, Treatment Outcome, Antibodies, Monoclonal therapeutic use, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Niacinamide analogs derivatives, and Phenylurea Compounds therapeutic use

Background: VEGF and VEGF receptor-2-mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis. Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor-2 antagonist. We aimed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following first-line therapy with sorafenib.
Methods: In this randomised, placebo-controlled, double-blind, multicentre, phase 3 trial (REACH), patients were enrolled from 154 centres in 27 countries. Eligible patients were aged 18 years or older, had hepatocellular carcinoma with Barcelona Clinic Liver Cancer stage C disease or stage B disease that was refractory or not amenable to locoregional therapy, had Child-Pugh A liver disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, had previously received sorafenib (stopped because of progression or intolerance), and had adequate haematological and biochemical parameters. Patients were randomly assigned (1:1) to receive intravenous ramucirumab (8 mg/kg) or placebo every 2 weeks, plus best supportive care, until disease progression, unacceptable toxicity, or death. Randomisation was stratified by geographic region and cause of liver disease with a stratified permuted block method. Patients, medical staff, investigators, and the funder were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01140347.
Findings: Between Nov 4, 2010, and April 18, 2013, 565 patients were enrolled, of whom 283 were assigned to ramucirumab and 282 were assigned to placebo. Median overall survival for the ramucirumab group was 9·2 months (95% CI 8·0-10·6) versus 7·6 months (6·0-9·3) for the placebo group (HR 0·87 [95% CI 0·72-1·05]; p=0·14). Grade 3 or greater adverse events occurring in 5% or more of patients in either treatment group were ascites (13 [5%] of 277 patients treated with ramucirumab vs 11 [4%] of 276 patients treated with placebo), hypertension (34 [12%] vs ten [4%]), asthenia (14 [5%] vs five [2%]), malignant neoplasm progression (18 [6%] vs 11 [4%]), increased aspartate aminotransferase concentration (15 [5%] vs 23 [8%]), thrombocytopenia (13 [5%] vs one [<1%]), hyperbilirubinaemia (three [1%] vs 13 [5%]), and increased blood bilirubin (five [2%] vs 14 [5%]). The most frequently reported (≥1%) treatment-emergent serious adverse event of any grade or grade 3 or more was malignant neoplasm progression.
Interpretation: Second-line treatment with ramucirumab did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma. No new safety signals were noted in eligible patients and the safety profile is manageable.
Funding: Eli Lilly and Co.
(Copyright © 2015 Elsevier Ltd. All rights reserved.)

BIOLOGICAL control of plant parasites, LEPIDOPTERA, ENTOMOPHAGOUS insects, PREDATORY insects, and HORTICULTURE

Pest suppression through biological control seeks to maximize the action of the pest's natural enemies with the goal of reducing pesticide use. We present a summary of published studies and original findings on several entomophagous species as biocontrol agents of Tuta absoluta (Meyrick, 1917) (Lepidoptera: Gelechiidae), a key pest of tomato crops in Argentina, with the aim to select potential candidates for its management. Spontaneously occurring T. absoluta egg parasitism was lower than that inflicted by the larval parasitoids Dineulophus phthorimaeae (De Santis, 1983) (Hymenoptera: Eulophidae) and Pseudapanteles dignus (Muesebeck, 1938) (Hymenoptera: Braconidae). These parasitoids exhibit important life history traits in laboratory conditions and produce relevant amounts of T. absoluta mortality in the field. Surveys carried out in Tucumán and Buenos Aires provinces, Argentina, revealed that D. phthorimaeae and P. dignus coexist in tomato and eggplant crops; T. absoluta- P. dignus interaction is also found on other non-cultivated solanaceous species present in horticultural farms. In addition, studies are currently under way to determine the predation ability of Zelus obscuridorsis (Stål, 1860) (Hemiptera: Reduviidae) on both larvae and adults of the pest. Finally, we discuss the prospects for implementing experimental augmentative releases of P. dignus to control the pest, a candidate selected considering various positive biological traits and because of its simple mass production and manipulation compared with other antagonists of T. absoluta. [ABSTRACT FROM AUTHOR]

Adenoma epidemiology, Adrenal Gland Neoplasms epidemiology, Adult, Cohort Studies, Female, Genetic Association Studies, Genetic Testing, Humans, Male, Middle Aged, Paraganglioma epidemiology, Pheochromocytoma epidemiology, Pituitary Neoplasms epidemiology, Young Adult, Adenoma genetics, Adrenal Gland Neoplasms genetics, Genetic Heterogeneity, Genetic Predisposition to Disease, Paraganglioma genetics, Pheochromocytoma genetics, and Pituitary Neoplasms genetics

Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence.
Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL.
Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples.
Setting: The study was conducted at university hospitals.
Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study.
Outcome: Outcomes included genetic screening and clinical characteristics.
Results: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context.
Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma.

CACAO diseases & pests, INSECT baits & repellents, INSECT pest control, KAOLIN, and HELOPELTIS

The use of particle film technology has not been documented previously to protect cacao (Theobroma cacao L.; Malvales: Malvaceae) against insect feeding. Laboratory assessment of the use of local kaolin against the cacao mirid bug, Helopeltis collaris Stal (Hemiptera: Miridae), revealed a highly positive and statistically significant repellence of this insect pest on kaolin-treated cacao pods. This result warrants follow up field studies to evaluate further the potential of kaolin clay to control cacao pests in the Philippines. [ABSTRACT FROM AUTHOR]

Adult, Aged, Blood Chemical Analysis, Case-Control Studies, Enzyme-Linked Immunosorbent Assay, Female, Hepcidins genetics, Humans, Kidney Failure, Chronic blood, Limit of Detection, Liver metabolism, Liver Diseases blood, Male, Middle Aged, RNA, Messenger metabolism, Tandem Mass Spectrometry, Young Adult, and Hepcidins blood

Background: Hepcidin-25 is a potential marker for iron disorders with a demand for accessible assays. This study aimed to evaluate a commercial competitive enzyme-linked immunosorbent assay (cELISA) for hepcidin quantitation.
Methods: Serum samples; 95 healthy subjects (HS), six patients with iron deficiency (ID), 84 patients with liver disorders (LD) and 220 hemodialysis patients (HD), were analyzed. Controls were used for imprecision, while accuracy was evaluated by quantitating hepcidin-25 with LC-MS/MS in 149 samples. Cross-reactivity for hepcidin-20 and hepcidin-22 was tested. Hepcidin-mRNA expression in 37 liver biopsies was measured.
Results: S-hepcidin ranged from 8-76 and 2-31 μg/L in healthy men and women. Levels in ID, LD and HD significantly differed from HS. Total coefficients of variation (CV) for controls were 24% and 22%. Within-sample CV was 10%. Despite a good correlation with LC-MS/MS (r = 0.89), the cELISA showed higher values and detected hepcidin-20 and hepcidin-22. Hepcidin-mRNA correlated well with S-hepcidin using cELISA and LC-MS/MS (r = 0.69 and 0.64).
Conclusions: The correlation with LC-MS/MS is good and the examined kit can differentiate between patient groups although it is not specific for hepcidin-25. Considering ELISA's capacity to readily be set up, the investigated kit can be applied. Specific reference ranges are required.

BROOD parasitism, STINKBUGS, INTRODUCED insects, BIOLOGICAL control of insects, and INSECT body composition

Native to eastern Asia, the brown marmorated stink bug (BMSB), Halyomorpha halys (Stål), has become a serious invasive pest in North America. Consequently, accurate assessment of parasitism rates under field conditions is critical for determining baseline parasitism rates of native egg parasitoids on BMSB, and for future evaluations of native or exotic parasitoid biological control release strategies and impacts. BMSB sentinel (laboratory-laid) egg masses have typically been used for this purpose, even though they could be providing misleading estimates of parasitoid activity. Accordingly, we compared the use of BMSB sentinel (laboratory-laid) and wild (naturally field-laid) egg masses in 2012 and 2013 to examine rates of parasitism and the parasitoid community composition of indigenous egg parasitoids in outdoor ornamental nurseries. Wild egg masses consistently had higher rates of parasitism than sentinel egg masses. In 2012, wild egg masses had a mean percent parasitism of 28.4% compared to 4.6% in sentinel egg masses, while in 2013 the difference between the two methods increased even further with a mean percent parasitism of 55.3% in wild egg masses compared to 0.8% in sentinel eggs. Furthermore, we found greater total numbers of parasitoids (889, 42) and greater species richness (seven, five), when using wild egg masses compared to sentinel egg masses, respectively. While sentinel egg masses provide a rapid and convenient way to assess the presence of natural enemies, our findings indicate that using sentinel egg masses could dramatically underestimate actual rates of parasitism and provide inaccurate estimates of parasitoid community composition. Future studies should address potential mechanisms underlying these patterns such as lack of certain host cues required by parasitoids in sentinel compared to wild egg masses. [ABSTRACT FROM AUTHOR]

The aim of this paper is to report the differential diagnosis undertaken in a 47-year-old patient who was admitted for severe pancytopenia at the Department of Internal Medicine, Tomas Bata Regional Hospital in Zlín in August 2012. As the initial examinations regarding inflammation, tumours, infections and systemic diseases were negative, myelodysplastic syndrome was suspected. Trephine biopsy was performed, but myelodysplastic syndrome was not confirmed. The patient quickly became dependent on transfusions and suffered from recurrent infections. The differential diagnostic process was further complicated by the patient's repeated refusal to be hospitalized at the department of Internal Medicine. Repeated CT scans showed increasing splenomegaly and eventually multiple osteoplastic and mixed deposits in the pelvic bone appeared, pointing to a probable malignancy. The patient was referred for further investigation to the Department of Internal Medicine, Haematology and Oncology Clinic, University Hospital Brno-Bohunice. The indicated whole-body PET/CT found extensive deposits of viable tumour tissue in the chest wall. Histological samples were taken and corticosteroid treatment was started. However, this resulted in tumour lysis syndrome followed by kidney failure. The patient developed multiple organ failure with disseminated intravascular coagulopathy and died on the day that the histological diagnosis of undifferentiated sarcoma was made. [ABSTRACT FROM AUTHOR]

Aldehydes chemistry, Benzamides chemistry, Catalysis, Cyclohexanones chemistry, Hydrophobic and Hydrophilic Interactions, Naphthalimides chemistry, Proline chemistry, Spectrometry, Fluorescence, Stereoisomerism, Water chemistry, Nanoparticles chemistry, and Polymers chemistry

Here, a modular approach is reported to introduce a specific function into single-chain polymeric nanoparticles (SCPNs). Hereto, an amphiphilic polymer with pendant benzene-1,3,5-tricarboxamide (BTA) units is mixed with a "free" BTA that contains a functional group, either a fluorescent naphthalimide or a catalytically active l-proline. Taking advantage of hydrophobic interactions and self-recognition properties of the BTA units, the "free" BTAs are captured into the interior of the SCPN in water as evidenced by fluorescence studies. To illustrate that function can be readily introduced using a modular approach, l-proline-based BTAs are incorporated to procure a catalytically active SCPN in water. The aldol reaction between p-nitrobenzaldehyde and cyclohexanone shows good conversions at low catalyst loadings and substrate concentrations, and high stereoselectivities are obtained (de = 91% and ee = 98%).
(© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

ESSENTIAL oils, REPELLENTS, STINKBUGS, HEMIPTERA, LEMONGRASS oil, SPEARMINT oil, and METHYL benzoate

The brown marmorated stink bug ( BMSB), Halyomorpha halys ( Stål), native to Northeastern Asia, is a serious invasive pest in the United States, Canada, Switzerland, Germany and France. Several common essential oils and their compositions were tested against BMSBs as potential repellents. All the tested individual essential oils and a ternary oil blend showed significant repellency to both BMSB nymphs and adults. Clove oil, lemongrass oil, spearmint oil, ylang-ylang oil, and the ternary oil mixture (clove, lemongrass and spearmint) almost completely blocked attraction of BMSBs to the stink bug attractant-baited traps; whereas wintergreen oil, geranium oil, pennyroyal oil and rosemary oil resulted in 60-85% trap catch reductions. Over 20 BMSB antennally active compounds were identified from SPME headspace samples of the eight repellent essential oils using GC- EAD and GC- MS techniques. Among the synthetic EAD-active compounds tested in the field, eugenol, l-carvone, p/l-menthone, pulegone, methyl salicylate, trans/ cis-citral, methyl benzoate and β-caryophyllene significantly reduced trap catches of BMSBs by 72-99%; these compounds are likely responsible for the repellency of their corresponding essential oils. Surprisingly, a synthetic mixture of the predacious spined soldier bug ( SSB) [ Podisus maculiventris (Say)] aggregation pheromone ( trans-2-hexenal, α-terpineol and benzyl alcohol) also showed a significant inhibition of BMSB response to its attractants. These repellent essential oils and their active compounds, as well as the synthetic SSB pheromone, are potentially useful as part of an efficient, environmentally sound semiochemical-based IPM programme to combat this serious invasive stink bug. [ABSTRACT FROM AUTHOR]

Aged, Female, Genome, Human, Genome-Wide Association Study, Hemochromatosis complications, Hemochromatosis pathology, Hemochromatosis Protein, Homozygote, Humans, Iron metabolism, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Hemochromatosis genetics, Histocompatibility Antigens Class I genetics, Liver Cirrhosis genetics, Membrane Proteins genetics, and Subtilisins genetics

Genome-wide association studies (GWAS) have revealed genetic determinants of iron metabolism, but correlation of these with clinical phenotypes is pending. Homozygosity for HFE C282Y is the predominant genetic risk factor for hereditary hemochromatosis (HH) and may cause liver cirrhosis. However, this genotype has a low penetrance. Thus, detection of yet unknown genetic markers that identify patients at risk of developing severe liver disease is necessary for better prevention. Genetic loci associated with iron metabolism (TF, TMPRSS6, PCSK7, TFR2 and Chr2p14) in recent GWAS and liver fibrosis (PNPLA3) in recent meta-analysis were analyzed for association with either liver cirrhosis or advanced fibrosis in 148 German HFE C282Y homozygotes. Replication of associations was sought in additional 499 Austrian/Swiss and 112 HFE C282Y homozygotes from Sweden. Only variant rs236918 in the PCSK7 gene (proprotein convertase subtilisin/kexin type 7) was associated with cirrhosis or advanced fibrosis (P = 1.02 × 10(-5)) in the German cohort with genotypic odds ratios of 3.56 (95% CI 1.29-9.77) for CG heterozygotes and 5.38 (95% CI 2.39-12.10) for C allele carriers. Association between rs236918 and cirrhosis was confirmed in Austrian/Swiss HFE C282Y homozygotes (P = 0.014; ORallelic = 1.82 (95% CI 1.12-2.95) but not in Swedish patients. Post hoc combined analyses of German/Swiss/Austrian patients with available liver histology (N = 244, P = 0.00014, ORallelic = 2.84) and of males only (N = 431, P = 2.17 × 10(-5), ORallelic = 2.54) were consistent with the premier finding. Association between rs236918 and cirrhosis was not confirmed in alcoholic cirrhotics, suggesting specificity of this genetic risk factor for HH. PCSK7 variant rs236918 is a risk factor for cirrhosis in HH patients homozygous for the HFE C282Y mutation.
(© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

In Arabidopsis thaliana, seven cyclin-dependent kinase (CDK) inhibitors have been identified, designated interactors of CDKs or Kip-related proteins (KRPs). Here, the function of KRP6 was investigated during cell cycle progression in roots infected by plant-parasitic root-knot nematodes. Contrary to expectations, analysis of Meloidogyne incognita-induced galls of KRP6-overexpressing lines revealed a role for this particular KRP as an activator of the mitotic cell cycle. In accordance, KRP6-overexpressing suspension cultures displayed accelerated entry into mitosis, but delayed mitotic progression. Likewise, phenotypic analysis of cultured cells and nematode-induced giant cells revealed a failure in mitotic exit, with the appearance of multinucleated cells as a consequence. Strong KRP6 expression upon nematode infection and the phenotypic resemblance between KRP6 overexpression cell cultures and root-knot morphology point toward the involvement of KRP6 in the multinucleate and acytokinetic state of giant cells. Along these lines, the parasite might have evolved to manipulate plant KRP6 transcription to the benefit of gall establishment.
(© 2014 American Society of Plant Biologists. All rights reserved.)

HEMIPTERA, ORYZA, PARASITOIDS, RICE, PLANTING, STINKBUGS, and PARASITES

The rice stem bug, Tibraca limbativentris Stal. (Hemiptera: Pentatomidae) is one of the most important pests of rice crops, especially irrigated crops. Plant defence strategies against these bugs may involve the emission of chemical compounds, which are released following herbivore attacks, directly or indirectly harming pest performance. The aim of this study was to evaluate the influence of constitutive and herbivory-induced volatiles from rice plants (Oryza sativa L.) on the behavioural responses of T. limbativentris adults and egg parasitoids Trissolcus basalis (Wollaston) and Telenomus podisi (Ashmead) (Hymenoptera, Platygastridae). Plant volatiles were collected from undamaged plants of the rice cultivar IRGA 424 and from plants that suffered herbivory by five males or five females of T. limbativentris. Air-entrainment extracts were analysed by GC–flame ionization detector and GC–MS, and insect responses evaluated in a ‘Y’ olfactometer. T. limbativentris feeding damaged on rice plants induced the release of 16 volatiles compounds in a higher amounts compared to undamaged plants The main compounds induced were (E)-2-hexenal, (E)-2-octen-1-ol, methyl salicylate and α-muurolene. Female bugs were significantly attracted to air-entrainment extracts containing volatiles from undamaged plants compared with air-entrainment extracts containing volatiles emitted from plants damaged by T. limbativentris, whereas males showed no preference. Telenomus podisi females were significantly attracted to volatiles from air-entrainment extracts of plants damaged by females, whereas T. basalis showed no preference. These results suggest that rice plants may be emitting defence compounds, which could be avoided by T. limbativentris females and also acted indirectly by attracting natural enemies. [ABSTRACT FROM AUTHOR]

Androstadienes therapeutic use, Antineoplastic Agents, Hormonal pharmacology, Aromatase Inhibitors therapeutic use, Biomarkers, Tumor genetics, Breast pathology, Breast Neoplasms genetics, Breast Neoplasms pathology, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Enzyme Activators pharmacology, ErbB Receptors antagonists inhibitors, Erlotinib Hydrochloride, Estrogen Receptor alpha antagonists inhibitors, Estrogen Receptor alpha genetics, Female, Gene Expression Regulation, Neoplastic, Genetic Association Studies, Genetic Variation, Humans, Letrozole, MCF-7 Cells, Nitriles therapeutic use, Protein Kinase Inhibitors pharmacology, Quinazolines pharmacology, RNA Interference, RNA, Small Interfering, Tamoxifen pharmacology, Tamoxifen therapeutic use, Toremifene pharmacology, Toremifene therapeutic use, Triazoles therapeutic use, Breast Neoplasms drug therapy, Drug Resistance, Neoplasm genetics, Estrogen Receptor alpha metabolism, Indazoles pharmacology, and Proto-Oncogene Proteins c-vav genetics

Introduction: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor α (ERα) are among the most effective systemic treatments for ERα-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through mechanisms that involve ERα transcriptional regulatory plasticity. Herein we identify VAV3 as a critical component in this process.
Methods: A cell-based chemical compound screen was carried out to identify therapeutic strategies against resistance to endocrine therapy. Binding to ERα was evaluated by molecular docking analyses, an agonist fluoligand assay and short hairpin (sh)RNA-mediated protein depletion. Microarray analyses were performed to identify altered gene expression. Western blot analysis of signaling and proliferation markers, and shRNA-mediated protein depletion in viability and clonogenic assays, were performed to delineate the role of VAV3. Genetic variation in VAV3 was assessed for association with the response to tamoxifen. Immunohistochemical analyses of VAV3 were carried out to determine its association with therapeutic response and different tumor markers. An analysis of gene expression association with drug sensitivity was carried out to identify a potential therapeutic approach based on differential VAV3 expression.
Results: The compound YC-1 was found to comparatively reduce the viability of cell models of acquired resistance. This effect was probably not due to activation of its canonical target (soluble guanylyl cyclase), but instead was likely a result of binding to ERα. VAV3 was selectively reduced upon exposure to YC-1 or ERα depletion, and, accordingly, VAV3 depletion comparatively reduced the viability of cell models of acquired resistance. In the clinical scenario, germline variation in VAV3 was associated with the response to tamoxifen in Japanese breast cancer patients (rs10494071 combined P value = 8.4 × 10-4). The allele association combined with gene expression analyses indicated that low VAV3 expression predicts better clinical outcome. Conversely, high nuclear VAV3 expression in tumor cells was associated with poorer endocrine therapy response. Based on VAV3 expression levels and the response to erlotinib in cancer cell lines, targeting EGFR signaling may be a promising therapeutic strategy.
Conclusions: This study proposes VAV3 as a biomarker and a rationale for its use as a signaling target to prevent and/or overcome resistance to endocrine therapy in breast cancer.

HEMIPTERA, HOST plants, RICE diseases & pests, ECHINOCHLOA, and REPRODUCTION

Obtaining eggs of Oebalus insularis Stal., for the multiplication of Telenomus podisi Ashmead depends on the quality of the food provided by diverse host plants. Therefore, the biological and reproductive performance of O. insularis on Oryza sativa L. and Echinochloa colona (L.) was determined at 28±2°C, 80 ± 5% of relative humidity and 12 hours photophase. The duration of the period of nymph eclosion until the emergence of the adult of O. insularis varied between 20,9 and 21,2 days, for O. sativa and E. colona, respectively. The longevity of the female and male of O. insularis was statistically similar on both host plants. The female longevity was higher than that shown by the male, varying between 15 and 12 days, respectively. The O. insularis female fed with E. colona presented a high number of eggs per batch, total number of eggs per female and the eclosion rate of nymphs was higher. The biological and reproductive parameters of this insect confirmed their adaptation to the alternative host E. colona, optimizing the production of eggs subjected to T. podisi parasitism. [ABSTRACT FROM AUTHOR]

SEROTONIN transporters, SEROTONIN uptake inhibitors, POSITRON emission tomography, CEREBRAL cortex, SOCIAL psychology, and MEDICAL imaging systems

Objective: This study examined the long-term effects of fluoxetine administered to juvenile rhesus monkeys who, as young adults, were imaged with positron emission tomography for two serotonergic markers: serotonin transporter (SERT) and serotonin 1A (5-HT1A) receptor. An equal number of monkeys separated from their mothers at birth-an animal model of human childhood stress-were also studied. Method: At birth, 32 male rhesus monkeys were randomly assigned to either maternal separation or normal rearing conditions. At age 2, half (N=8) of each group was randomly assigned to fluoxetine (3 mg/kg) or placebo for 1 year. To eliminate the confounding effects of residual drug in the brain, monkeys were scanned at least 1.5 years after drug discontinuation. Social interactions were assessed both during and after drug administration. Results: Fluoxetine persistently upregulated SERT, but not 5-HT1A receptors, in both the neocortex and the hippocampus. Whole-brain voxel-wise analysis revealed that fluoxetine had a significant effect in the lateral temporal and cingulate cortices. In contrast, neither maternal separation by itself nor the rearing-by-drug interaction was significant for either marker. Fluoxetine had no significant effect on the behavioral measures. Conclusions: Fluoxetine administered to juvenile monkeys upregulates SERT into young adulthood. Implications regarding the efficacy or potential adverse effects of SSRIs in patients cannot be directly drawn from this study. Its purpose was to investigate effects of SSRIs on brain development in nonhuman primates using an experimental approach that randomly assigned long-term SSRI treatment or placebo. [ABSTRACT FROM AUTHOR]

Biomarkers, Tumor metabolism, Breast Neoplasms genetics, Breast Neoplasms metabolism, Cadherins metabolism, Colorectal Neoplasms genetics, Colorectal Neoplasms metabolism, Epithelial-Mesenchymal Transition genetics, Gene Expression Regulation, Neoplastic genetics, Homeodomain Proteins metabolism, Humans, Immunohistochemistry, In Situ Hybridization, Laser Capture Microdissection, Liver Neoplasms secondary, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Survival Analysis, Transcription Factors metabolism, Zinc Finger E-box-Binding Homeobox 1, Breast Neoplasms physiopathology, Colorectal Neoplasms physiopathology, Epithelial-Mesenchymal Transition physiology, Gene Expression Regulation, Neoplastic physiology, Liver Neoplasms metabolism, MicroRNAs metabolism, and Signal Transduction physiology

The role of the epithelial-mesenchymal transition (EMT) in cancer has been studied extensively in vitro, but involvement of the EMT in tumorigenesis in vivo is largely unknown. We investigated the potential of microRNAs as clinical markers and analyzed participation of the EMT-associated microRNA-200-ZEB-E-cadherin pathway in cancer progression. Expression of the microRNA-200 family was quantified by real-time RT-PCR analysis of fresh-frozen and microdissected formalin-fixed paraffin-embedded primary colorectal tumors, normal colon mucosa, and matched liver metastases. MicroRNA expression was validated by in situ hybridization and after in vitro culture of the malignant cells. To assess EMT as a predictive marker, factors considered relevant in colorectal cancer were investigated in 98 primary breast tumors from a treatment-randomized study. Associations between the studied EMT-markers were found in primary breast tumors and in colorectal liver metastases. MicroRNA-200 expression in epithelial cells was lower in malignant mucosa than in normal mucosa, and was also decreased in metastatic compared to non-metastatic colorectal cancer. Low microRNA-200 expression in colorectal liver metastases was associated with bad prognosis. In breast cancer, low levels of microRNA-200 were related to reduced survival and high expression of microRNA-200 was predictive of benefit from radiotheraphy. MicroRNA-200 was associated with ER positive status, and inversely correlated to HER2 and overactivation of the PI3K/AKT pathway, that was associated with high ZEB1 mRNA expression. Our findings suggest that the stability of microRNAs makes them suitable as clinical markers and that the EMT-related microRNA-200-ZEB-E-cadherin signaling pathway is connected to established clinical characteristics and can give useful prognostic and treatment-predictive information in progressive breast and colorectal cancers.

Introduction. Current curative treatment of acute myeloid leukemia is based on intensive chemotherapy and hematopoietic stem cell transplantation with a significant risk of severe adverse effects, including leukemogenic and cancerogenic ones. Objectives. The study is aimed at assessing of incidence and types of malignant tumours in successfully treated acute myeloid leukemia patients. Methods. A retrospective analysis consists of 256 patients diagnosed with acute myeloid leukemia at the Department of Hemato-Oncology in Olomouc in 1996-2008 who were treated with intensive chemotherapy and achieved complete remission of the disease. Results. Second malignancy occurred in 11 individuals (4.3%) after successful treatment of acute myeloid leukemia. Observed age-standardized incidence of these tumours, 8.29/1,000 person-years, 95% Cl = (2.99; 13.58), was not significantly different from the incidence in population. Five patients died of the second malignancy. [ABSTRACT FROM AUTHOR]

Animals, Bacillus thuringiensis Toxins, Binding Sites, Insect Control, Insect Proteins metabolism, Microvilli metabolism, Peptide Hydrolases metabolism, Proteolysis, Bacterial Proteins metabolism, Endotoxins metabolism, Hemiptera metabolism, and Hemolysin Proteins metabolism

To understand the low toxicity of Cry toxins in planthoppers, proteolytic activation of Cry1Ab in Nilaparvata lugens was studied. The proteolytic processing of Cry1Ab protoxin by N. lugens midgut proteases was similar to that by trypsin activated Cry1Ab. The Cry1Ab processed with N. lugens midgut proteases was highly insecticidal against Plutella xylostella. However, Cry1Ab activated either by trypsin or the gut proteases of the brown planthopper showed low toxicity in N. lugens. Binding analysis showed that activated Cry1Ab bound to brush border membrane vesicles (BBMV) from N. lugens at a significantly lower level than to BBMV from P. xylostella.
(Copyright © 2013 Elsevier Inc. All rights reserved.)

Escherichia coli isolation purification, Escherichia coli Infections microbiology, Humans, Microbial Sensitivity Tests methods, Microbial Sensitivity Tests standards, Sepsis microbiology, beta-Lactam Resistance, Amoxicillin pharmacology, Anti-Bacterial Agents pharmacology, Clavulanic Acid pharmacology, and Escherichia coli drug effects

Objectives: The CLSI recommends a fixed 2 : 1 ratio of co-amoxiclav for broth microdilution susceptibility testing of Enterobacteriaceae, while EUCAST recommends a fixed 2 mg/L clavulanate concentration. The aims of this study were: (i) to determine the influence of a switch from CLSI to EUCAST methodology on Escherichia coli susceptibility rates; (ii) to compare susceptibility results obtained using EUCAST-compliant microdilution with those from disc diffusion and the Etest; and (iii) to evaluate the clinical outcome of patients with E. coli sepsis treated with co-amoxiclav in relation to the susceptibility results obtained using either method.
Methods: Resistance rates were determined in three laboratories that switched from CLSI to EUCAST cards with the Phoenix system (Becton Dickinson) as well as in 17 laboratories that continued to use CLSI cards with the VITEK 2 system (bioMérieux). In one laboratory, isolates were simultaneously tested by both the Phoenix system and either disc diffusion (n = 471) or the Etest (n = 113). Medical and laboratory records were reviewed for E. coli sepsis patients treated with co-amoxiclav monotherapy.
Results: Only laboratories that switched methodology showed an increase in resistance rates - from 19% in 2010 to 31% in 2011 (P < 0.0001). All isolates that tested susceptible by microdilution were also susceptible by disc diffusion or the Etest, but of 326 isolates that tested resistant by microdilution, 43% and 59% tested susceptible by disc diffusion and the Etest, respectively. Among the 89 patients included there was a better correlation between clinical response and measured MICs using the Phoenix system than the Etest.
Conclusions: EUCAST methodology resulted in higher co-amoxiclav E. coli resistance rates than CLSI methodology, but correlated better with clinical outcome. EUCAST-compliant microdilution and disc diffusion provided discrepant results.

HEMIPTERA, COREIDAE, INSECT development, OPUNTIA, and FEROCACTUS

Narnia femorata Stål (Hemiptera: Heteroptera: Coreidae) is a leaffooted bug commonly found on Opuntia and Ferocactus cacti (Cactaceae) in southern New Mexico. Although general information has been published on the biology of this species, detailed studies are limited, particularly in America north of Mexico. Therefore, we conducted a study of this bug's life history in southern New Mexico from August 2010 to May 2012, reared the bug in the laboratory, and described the immature stages. Six prickly pear cactus plants, Opuntia phaeacantlut Engelmann, and four barrel cactus plants, Ferocactus wislizeni (Engelmann) Britton & Rose, were examined weekly to record numbers of the various life stages, adult sex ratios, and behavioral activities. Adults of this apparently bivoltine species overwintered in plant debris at the bases of their host plants. They emerged in late February to deposit eggs in rows along the underside of cactus spines. Nymphs were found from late February through late December. Nymphs of the first generation were most abundant April through June on and around developing flowers of O. phaeacantha. Those of the second generation were most abundant during August and September on maturing fruit of O. phaeacantha and developing flowers and maturing fruit of F. wislizeni. The bug also was reared from egg to adult under controlled laboratory conditions on fruit and pads of O. phaeacantha at 25 ± 0.01°C under a photoperiod of 14:10 (L:D) h. The incubation period averaged 12.70 d. The five stadia averaged 3.84, 11.00, 12.12, 17.06, and 22.94 d, respectively. Instars can be distinguished readily by differences in several morphological features in addition to body size and coloration. [ABSTRACT FROM AUTHOR]

Animals, Bacterial Proteins genetics, Chi-Square Distribution, DNA, Bacterial analysis, DNA, Bacterial genetics, Drug Resistance, Bacterial, Escherichia coli genetics, Escherichia coli isolation purification, Escherichia coli Infections microbiology, Humans, Microbial Sensitivity Tests, beta-Lactamases metabolism, Anti-Bacterial Agents pharmacology, Escherichia coli drug effects, Escherichia coli enzymology, Meat microbiology, Poultry microbiology, and beta-Lactamases genetics

The concurrent presence of bla CTX-M-1 and bla TEM-52 genes on similar plasmids of Escherichia coli isolated from poultry, chicken meat and humans supports the occurrence of food-borne transmission of extended-spectrum beta-lactamase (ESBL) genes. ESBL-producing E. coli (ESBL-E. coli) are most frequently detected in hospitalised patients and are known to spread in healthcare settings. We hypothesised that poultry-associated (PA) ESBL genes are predominant in the community, where acquisition is fuelled by food contamination, whereas non-PA ESBL genes are predominant in hospitals, with acquisition fuelled by cross-transmission. Then, differences in antimicrobial selective pressure in hospitals and poultry would create differences in co-resistance between PA and non-PA ESBL-E. coli. We, therefore, determined the prevalence and co-resistance of PA and non-PA ESBL-E. coli in community-acquired and nosocomial urinary tract infections in humans and bla CTX-M-1 and bla TEM-52 isolates from poultry. A total of 134 human ESBL-E. coli urine isolates were included in this study. Isolates containing bla CTX-M-1 or bla TEM-52 were considered to be PA, with the remainder being non-PA. Also, 72 poultry ESBL-E. coli were included. Minimum inhibitory concentration (MIC) values were determined by broth microdilution. The prevalence of PA ESBL genes in isolates obtained in general practice and hospitals was 28 % versus 30 % (n.s.). Human PA ESBL-E. coli were more frequently susceptible to ciprofloxacin (51 % vs. 25 %; p = 0.0056), gentamicin (86 % vs. 63 %; p = .0.0082), tobramycin (91 % vs. 34 %; p = 0.0001) and amikacin (98 % vs. 67 %; p = 0.0001) compared to human non-PA ESBL-E. coli. PA ESBL-E. coli are not more prevalent in community acquired than nosocomial urine samples, but are more often susceptible to ciprofloxacin and aminoglycosides than non-PA ESBL-E. coli. This does not support the existence of different reservoirs of ESBL genes.

Give 'em structure: The presence of structuring elements in polymers that were functionalized with catalytic units resulted in a new class of enzyme mimics, which are only active in the folded state (see picture). The conformationally adaptive hydrophobic environment that surrounds the catalytic site allows the very efficient catalysis of an aldol reaction in water with Michaelis–Menten kinetics. [ABSTRACT FROM AUTHOR]

Biomarkers, Tumor metabolism, Female, Humans, Middle Aged, Phosphorylation, Postmenopause, Predictive Value of Tests, Receptors, Estrogen metabolism, Retrospective Studies, Serine metabolism, Treatment Outcome, Antineoplastic Agents, Hormonal pharmacology, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Proto-Oncogene Proteins c-akt metabolism, TOR Serine-Threonine Kinases metabolism, and Tamoxifen pharmacology

The frequent alterations of the PI3K/Akt/mTOR-growth signaling pathway are proposed mechanisms for resistance to endocrine therapy in breast cancer, partly through regulation of estrogen receptor α (ER) activity. Reliable biomarkers for treatment prediction are required for improved individualized treatment. We performed a retrospective immunohistochemical analysis of primary tumors from 912 postmenopausal patients with node-negative breast cancer, randomized to either tamoxifen or no adjuvant treatment. Phosphorylated (p) Akt-serine (s) 473, p-mTOR-s2448, and ER phosphorylations-s167 and -s305 were evaluated as potential biomarkers of prognosis and tamoxifen treatment efficacy. High expression of p-mTOR indicated a reduced response to tamoxifen, most pronounced in the ER+/progesterone receptor (PgR) + subgroup (tamoxifen vs. no tamoxifen: hazard ratio (HR), 0.86; 95 % confidence interval (CI), 0.31-2.38; P = 0.78), whereas low p-mTOR expression predicted tamoxifen benefit (HR, 0.29; 95 % CI, 0.18-0.49; P = 0.000002). In addition, nuclear p-Akt-s473 as well as p-ER at -s167 and/or -s305 showed interaction with tamoxifen efficacy with borderline statistical significance. A combination score of positive pathway markers including p-Akt, p-mTOR, and p-ER showed significant association with tamoxifen benefit (test for interaction; P = 0.029). Cross-talk between growth signaling pathways and ER-signaling has been proposed to affect tamoxifen response in hormone receptor-positive breast cancer. The results support this hypothesis, as an overactive pathway was significantly associated with reduced response to tamoxifen. A clinical pre-treatment test for cross-talk markers would be a step toward individualized adjuvant endocrine treatment with or without the addition of PI3K/Akt/mTOR pathway inhibitors.

DIAGNOSIS of diabetes, KIDNEY disease diagnosis, LIVER, GENETIC polymorphisms, GENETICS, GENETIC mutation, and ANATOMY

Diabet. Med. 30, 114-117 (2013) Abstract Aims Hepatocyte nuclear factor 1β ( HNF1B) mutations cause a syndrome of renal cysts and diabetes, with whole gene deletions accounting for approximately 50% of cases. The severity of the renal phenotype is variable, from enlarged cystic kidneys incompatible with life to normal renal development and function. We investigated the prevalence of HNF1B deletions in patients with diabetes but no known renal disease. Methods We tested 461 patients with familial diabetes diagnosed before 45 years, including 258 probands who met clinical criteria for maturity-onset diabetes of the young (two generations affected and at least one family member diagnosed under 25 years). A fluorescent polymerase chain reaction assay was used to analyse two intragenic polymorphic HNF1B markers and identify heterozygous patients who therefore did not have whole gene deletions. Those patients homozygous for both markers were then tested for an HNF1B deletion using multiplex ligation-dependent probe amplification. Results Heterozygous HNF1B intragenic polymorphisms were identified in 337/461 subjects. Multiplex ligation-dependent probe amplification analysis showed an HNF1B gene deletion in three of the remaining 124 probands, all of whom met the criteria for maturity-onset diabetes of the young. Testing of their relatives identified three additional deletion carriers and ultrasound scanning showed renal developmental abnormalities in three of these six patients. Conclusions We estimate that HNF1B mutations account for < 1% of cases of maturity-onset diabetes of the young. Although HNF1B mutations are a rare cause of diabetes in the absence of known renal disease, a genetic diagnosis of renal cysts and diabetes syndrome is important as it raises the possibility of subclinical renal disease and the 50% risk of renal cysts and diabetes syndrome in the patient's offspring. [ABSTRACT FROM AUTHOR]

STINKBUGS, DIAPAUSE, RICE diseases & pests, ANDROPOGON, PESTS, PLANT parasites, and REPRODUCTION

The rice stalk stink bug, Tibraca limbativentris Stål (Hemiptera: Pentatomidae), is a major pest of rice crops throughout Latin America. We investigated the occurrence of diapause in T. limbativentris, as well as the role of West Indian foxtail, Andropogon bicornis L.(Poaceae), in its seasonal abundance and mortality. This plant grows spontaneously in grasslands from Mexico to Argentina, including at the edges of rice fields in southern Brazil. Tussocks of A. bicornis were collected in Eldorado do Sul, State of Rio Grande do Sul, Brazil throughout one yr and examined to sample rice stalk stink bugs. We collected in 2,355 T. limbativentris adults from 208 tussocks, totalling 2,205 live and 150 dead individuals. Live insects were dissected to determine the reproductive stage and to assess the presence of the fat body. We describe the occurrence of imaginal diapause and the use of A. bicornis as a shelter for this rice pest. Overwintering lasted 7 mo; arrival at the refuge occurred in early autumn (late Mar); the permanence period began in Jun, and extended to the end of Sep. From Oct the population decreased gradually until total departure from the tussocks in Jan. Thus, here we highlight the role of A. bicornis as an hibernation site for T. limbativentris in southern Brazil. [ABSTRACT FROM AUTHOR]

REOVIRUSES, CHINESE mitten crab, VIRION, and FRESHWATER crabs

A second type of freshwater crab reovirus has been isolated from Chinese mitten crab, Eriocheir sinensis H. Milne Edwards, in China; we named it E. sinensis reovirus ( EsRV816). The negatively stained virion is a non-enveloped icosahedral particle, 60 ± 5 nm in diameter. Its genome is composed of 10 dsRNA linear pieces exhibiting an electrophoretic pattern of 5/3/2. The largest segment (RNA-1) was cloned and sequenced. The deduced amino acid sequence, corresponding to the RdRp of the virus, showed 26% identity with the RdRp of Operophtera brumata (L.) cypovirus 19 in the genus Cypovirus and 24% identity with RdRp of Nilaparvata lugens (Stal) reovirus in the genus Fijivirus. On the basis of its ultrastructure and physicochemical properties, this virus is quite different from other crab reoviruses, and particularly with another freshwater crab reovirus EsRV905, recently classified in a new genus Cardoreovirus. This virus ( EsRV816) possesses all the characters of the members of the reoviridae family and could represent a new genus. [ABSTRACT FROM AUTHOR]

Biota, DNA Primers genetics, Databases, Genetic, Ecology methods, Microsatellite Repeats, and Polymorphism, Single Nucleotide

This article documents the addition of 473 microsatellite marker loci and 71 pairs of single-nucleotide polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Barteria fistulosa, Bombus morio, Galaxias platei, Hematodinium perezi, Macrocentrus cingulum Brischke (a.k.a. M. abdominalis Fab., M. grandii Goidanich or M. gifuensis Ashmead), Micropogonias furnieri, Nerita melanotragus, Nilaparvata lugens Stål, Sciaenops ocellatus, Scomber scombrus, Spodoptera frugiperda and Turdus lherminieri. These loci were cross-tested on the following species: Barteria dewevrei, Barteria nigritana, Barteria solida, Cynoscion acoupa, Cynoscion jamaicensis, Cynoscion leiarchus, Cynoscion nebulosus, Cynoscion striatus, Cynoscion virescens, Macrodon ancylodon, Menticirrhus americanus, Nilaparvata muiri and Umbrina canosai. This article also documents the addition of 116 sequencing primer pairs for Dicentrarchus labrax.
(© 2012 Blackwell Publishing Ltd.)

Animals, Brazil, DNA, Bacterial analysis, Hemiptera classification, Insect Vectors classification, Phytoplasma classification, Phytoplasma genetics, Phytoplasma isolation purification, Polymerase Chain Reaction, Population Density, Sequence Analysis, DNA, Species Specificity, Citrus microbiology, Hemiptera microbiology, Insect Vectors microbiology, Phytoplasma physiology, Plant Diseases microbiology, and Plant Weeds growth development

Huanglongbing (HLB) is a severe citrus (Citrus spp.) disease associated with the bacteria genus Candidatus Liberibacter, detected in Brazil in 2004. Another bacterium was found in association with HLB symptoms and characterized as a phytoplasma belonging to the 16SrIX group. The objectives of this study were to identify potential leafhopper vectors of the HLB-associated phytoplasma and their host plants. Leafhoppers were sampled every other week for 12 mo with sticky yellow cards placed at two heights (0.3 and 1.5 m) in the citrus tree canopy and by using a sweep net in the ground vegetation of two sweet orange, Citrus sinensis (L.) Osbeck, groves infected by the HLB-phytoplasma in São Paulo state. Faunistic analyses indicated one Agalliinae (Agallia albidula Uhler) and three Deltocephalinae [Balclutha hebe (Kirkaldy), Planicephalus flavicosta (Stål), and Scaphytopius (Convelinus) marginelineatus (Stål)] species, as the most abundant and frequent leafhoppers (Hemiptera: Cicadellidae). Visual observations indicated an association of leafhopper species with some weeds and the influence of weed species composition on leafhopper abundance in low-lying vegetation. S. marginelineatus and P. flavicosta were more frequent on Sida rhombifolia L. and Althernantera tenella Colla, respectively, whereas A. albidula was observed more often on Conyza bonariensis (L.) Cronq. and B. hebe only occurred on grasses. DNA samples of field-collected S. marginelineatus were positive by polymerase chain reaction and sequencing tests for the presence of the HLB-phytoplasma group, indicating it as a potential vector. The association of leafhoppers with their hosts may be used in deciding which management strategies to adopt against weeds and diseases in citrus orchards.

PARENTAL behavior in animals, BELOSTOMA, INSECT evolution, SEXUAL dimorphism in animals, MULTIVARIATE analysis, INSECT adaptation, and INSECTS

Current evidence suggests that sexual size dimorphism (SSD) reflects the male and female adaptation to their different reproductive roles. Belostoma and Lethocerus species, included in Belostomatidae, present different kinds of paternal care. Females of Belostoma Latreille species lay their eggs on the back of males. Males carry, aerate and protect the clutch until hatching, which is critical for offspring survival. Males of Lethocerus Mayr species exhibit some parental care behavior but do not carry the eggs. The genera are nearly related. We studied and compared the SSD patterns of B. oxyurum (Dufour), B. micantulum (Stål), B. elegans (Mayr), B. bifoveolatum Spinola, B. gestroi Montandon and Lethocerus annulipes (Herrich-Schäffer) by means of a multivariate approach to distinguish selection targets in different components of size. Morphometric analysis revealed that SSD patterns vary among traits and that the arrangements are similar in Belostoma species, showing a common trend under resembling selective mechanisms. The widespread SSD trend in insects is that all components of body size are biased towards females, generally related to a fecundity advantage, a pattern now also detected in L. annulipes. We found in Belostoma species that the male has relatively longer middle and hind legs. We propose that SSD in hind legs biased towards males is a selective response for paternal care; they denote a brood-adapted morphology. The middle leg enlargement may be an associated response to maintain effective locomotion. [ABSTRACT FROM AUTHOR]