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Guimier A, de Pontual L, Braddock SR, Torti E, Pérez-Jurado LA, Muñoz-Cabello P, Arumí M, Monaghan KG, Lee H, Wang LK, Pluym ID, Lynch SA, Stals K, Ellard S, Muller C, Houyel L, Cohen L, Lyonnet S, Bajolle F, Amiel J, and Gordon CT
Human molecular genetics [Hum Mol Genet] 2023 Jan 13; Vol. 32 (3), pp. 353-356.
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Humans, Heart Defects, Congenital, and Truncus Arteriosus, Persistent
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Vendrik KEW, Kuijper EJ, Dimmendaal M, Silvis W, Denie-Verhaegh E, de Boer A, Postma B, Schoffelen AF, Ruijs WLM, Koene FMHPA, Petrignani M, Hooiveld M, Witteveen S, Schouls LM, and Notermans DW
Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin [Euro Surveill] 2022 Dec; Vol. 27 (49).
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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
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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.
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Noordermeer T, Schutgens REG, Visser C, Rademaker E, de Maat MPM, Jansen AJG, Limper M, Cremer OL, Kruip MJHA, Endeman H, Maas C, de Laat B, and Urbanus RT
Research and practice in thrombosis and haemostasis [Res Pract Thromb Haemost] 2022 Sep 16; Vol. 6 (6), pp. e12809. Date of Electronic Publication: 2022 Sep 16 (Print Publication: 2022).
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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).)
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Ismail, Vardha, Zachariassen, Linda G., Godwin, Annie, Sahakian, Mane, Ellard, Sian, Stals, Karen L., Baple, Emma, Brown, Kate Tatton, Foulds, Nicola, Wheway, Gabrielle, Parker, Matthew O., Lyngby, Signe M., Pedersen, Miriam G., Desir, Julie, Bayat, Allan, Musgaard, Maria, Guille, Matthew, Kristensen, Anders S., and Baralle, Diana
- American Journal of Human Genetics. July 7, 2022, Vol. 109 Issue 7, 1217
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Cruces L, de la Peña E, and De Clercq P
Journal of insect science (Online) [J Insect Sci] 2022 Jul 01; Vol. 22 (4).
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Animals, Biology, Diet, Female, Nymph growth development, Ovum, Heteroptera growth development, Temperature, and Zea mays
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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.)
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Kawagoe, James C, Abrams, Adelaine E, Lourie, Austin P, and Walse, Spencer S
- Pest Management Science; Jul2022, Vol. 78 Issue 7, p3090-3097, 8p
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STINKBUGS, BROWN marmorated stink bug, CARBON dioxide, FUMIGATION, ATMOSPHERIC carbon dioxide, HEMIPTERA, and DILUTION
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BACKGROUND: The brown marmorated stink bug (BMSB), Halyomorpha halys, has caused significant agricultural damage to numerous hosts, so agricultural producers seek to limit its spread. Where established, BMSB can also cause substantial urban and commercial disturbance, as overwintering adults may seek refuge inside dwellings, covered spaces, vehicles, and consignments. Phytosanitary authorities are most concerned with the importation of 'hitchhiking' adults in this refugia, with certain countries requiring a quarantine treatment to mitigate risk. This study explores fumigation with ethyl formate, applied as 16.7% by mass dilution in carbon dioxide, for control of adult BMSB. RESULTS: The induction of diapause, to simulate overwintering physiology, resulted in 2‐ and 3‐fold increases in the tolerance of adults toward this ethyl formate fumigation at 10 ± 0.5 °C (x¯±2s) lasting for 8 and 12 h, respectively. However, a decreased tolerance (0.7‐fold) of diapausing specimens was observed for a 4‐h duration. Diapausing and nondiapausing adult BMSB can be controlled at the probit 9 level if the headspace concentration of ethyl formate, [EF], in the carbon dioxide mixture is maintained ≥7.68 mg L−1 for 12 h at 10 ± 0.5 °C (x¯±2s). If the duration is shortened to 4 h, [EF] must be maintained ≥14.73 mg L−1 over the course of fumigation. CONCLUSION: The toxicity of ethyl formate in this mixture can be distinct for different physiological states of the same life stage, as evidenced by a ca. 3‐fold increase in the Haber's z parameter for adult BMSB when in diapause. Respective to the physiological state of adults, this study identifies how the applied dose and/or treatment duration can be modulated (i.e. tuned) to ensure adequate toxicological efficacy toward BMSB infesting hosts or refuge at temperatures ca. >10 °C. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]
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Leers, Math P. G., Deneer, Ruben, Mostard, Guy J. M., Mostard, Remy L. M., Boer, Arjen-Kars, Scharnhorst, Volkher, Stals, Frans, Kleinveld, Henne A., and van Dam, Dirk W.
PLoS ONE . 6/28/2022, Vol. 17 Issue 6, p1-12. 12p.
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MEDICAL personnel, BLOOD testing, COVID-19 testing, SICK leave, and HOSPITALS
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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]
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Cruces L, de la Peña E, Livia C, and De Clercq P
Neotropical entomology [Neotrop Entomol] 2022 Jun 21. Date of Electronic Publication: 2022 Jun 21.
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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.)
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Panizzi, A. R. and Lucini, T. L.
- Arthropod - Plant Interactions. February, 2022, Vol. 16 Issue 1, p1, 14 p.
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Phillips, Eleanor F., Allan, Sandra A., and Gillett-Kaufman, Jennifer L.
Florida Entomologist . Dec2021, Vol. 104 Issue 4, p265-273. 9p.
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STINKBUGS, OLIVE fly, OLIVE, FRUIT development, BROWN marmorated stink bug, INTRODUCED organisms, and LEAFHOPPERS
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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]
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Abrams, Adelaine E., Alvarez, Alfredo, Rodriguez, Matthew S., Kron, Cindy R., Bellamy, Dave E., and Walse, Spencer S.
- Journal of Economic Entomology. December, 2021, Vol. 114 Issue 6, p2297, 10 p.
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Pirzadian J, Persoon MC, Severin JA, Klaassen CHW, de Greeff SC, Mennen MG, Schoffelen AF, Wielders CCH, Witteveen S, van Santen-Verheuvel M, Schouls LM, and Vos MC
Scientific reports [Sci Rep] 2021 Oct 25; Vol. 11 (1), pp. 21015. Date of Electronic Publication: 2021 Oct 25.
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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
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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).)
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Gariepy, Tara D., Musolin, Dmitry L., Konjević, Aleksandra, Karpun, Natalia N., Zakharchenko, Vilena Y., Zhuravleva, Elena N., Tavella, Luciana, Bruin, Allison, and Haye, Tim
NeoBiota . 9/30/2021, Vol. 68, p53-77. 25p.
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STINKBUGS, BROWN marmorated stink bug, CYTOCHROME oxidase, GENETIC variation, and HEMIPTERA
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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]
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Kaptein, F H J, Stals, M A M, Klaase, E, Kapteijn, M Y, Cannegieter, S C, Taphoorn, M J B, Dirven, L, Huisman, M V, Koekkoek, J A F, and Klok, F A
- Neuro-Oncology; 2021 Supplement, Vol. 23, pii38-ii38, 1p
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Bulgarini, Giacomo, Castracani, Cristina, Mori, Alessandra, Grasso, Donato A., and Maistrello, Lara
Entomologia Experimentalis et Applicata . Sep2021, Vol. 169 Issue 9, p799-806. 8p.
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BROWN marmorated stink bug, PREDATORY insects, ORCHARDS, ANTS, HYMENOPTERA, and PREDATORY animals
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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]
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Bout A, Tortorici F, Hamidi R, Warot S, Tavella L, and Thomas M
Insects [Insects] 2021 Aug 24; Vol. 12 (9). Date of Electronic Publication: 2021 Aug 24.
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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.
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Cornelius, Mary L., Vinyard, Bryan T., Weber, Donald C., and Greenstone, Matthew H.
- Journal of Economic Entomology. April, 2021, Vol. 114 Issue 2, p590, 7 p.
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Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V, Sanyal AJ, Sejling AS, and Harrison SA
The New England journal of medicine [N Engl J Med] 2021 Mar 25; Vol. 384 (12), pp. 1113-1124. Date of Electronic Publication: 2020 Nov 13.
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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
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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.)
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Radio FC, Pang K, Ciolfi A, Levy MA, Hernández-García A, Pedace L, Pantaleoni F, Liu Z, de Boer E, Jackson A, Bruselles A, McConkey H, Stellacci E, Lo Cicero S, Motta M, Carrozzo R, Dentici ML, McWalter K, Desai M, Monaghan KG, Telegrafi A, Philippe C, Vitobello A, Au M, Grand K, Sanchez-Lara PA, Baez J, Lindstrom K, Kulch P, Sebastian J, Madan-Khetarpal S, Roadhouse C, MacKenzie JJ, Monteleone B, Saunders CJ, Jean Cuevas JK, Cross L, Zhou D, Hartley T, Sawyer SL, Monteiro FP, Secches TV, Kok F, Schultz-Rogers LE, Macke EL, Morava E, Klee EW, Kemppainen J, Iascone M, Selicorni A, Tenconi R, Amor DJ, Pais L, Gallacher L, Turnpenny PD, Stals K, Ellard S, Cabet S, Lesca G, Pascal J, Steindl K, Ravid S, Weiss K, Castle AMR, Carter MT, Kalsner L, de Vries BBA, van Bon BW, Wevers MR, Pfundt R, Stegmann APA, Kerr B, Kingston HM, Chandler KE, Sheehan W, Elias AF, Shinde DN, Towne MC, Robin NH, Goodloe D, Vanderver A, Sherbini O, Bluske K, Hagelstrom RT, Zanus C, Faletra F, Musante L, Kurtz-Nelson EC, Earl RK, Anderlid BM, Morin G, van Slegtenhorst M, Diderich KEM, Brooks AS, Gribnau J, Boers RG, Finestra TR, Carter LB, Rauch A, Gasparini P, Boycott KM, Barakat TS, Graham JM Jr, Faivre L, Banka S, Wang T, Eichler EE, Priolo M, Dallapiccola B, Vissers LELM, Sadikovic B, Scott DA, Holder JL Jr, and Tartaglia M
American journal of human genetics [Am J Hum Genet] 2021 Mar 04; Vol. 108 (3), pp. 502-516. Date of Electronic Publication: 2021 Feb 16.
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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
- Abstract
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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.)
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Álvarez, Leopoldo J., Bernardis, Adela M., Defea, Bárbara S., Dellapé, Pablo M., Del Río, María G., Gittins López, Cecilia G., Lanteri, Analía A., López Armengol, María F., Marino De Remes Lenicov, Ana M., Minghetti, Eugenia, Paradell, Susana L., and Rizzo, María E.
- Revista de la Sociedad Entomológica Argentina. March, 2021, Vol. 80 Issue 1, p48, 22 p.
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