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Adult, Humans, Prospective Studies, Cross-Sectional Studies, Models, Statistical, Prognosis, Fibrin Fibrinogen Degradation Products analysis, Venous Thromboembolism diagnosis, Venous Thromboembolism epidemiology, Pulmonary Embolism diagnosis, and Pulmonary Embolism epidemiology

Aims: Risk stratification is used for decisions regarding need for imaging in patients with clinically suspected acute pulmonary embolism (PE). The aim was to develop a clinical prediction model that provides an individualized, accurate probability estimate for the presence of acute PE in patients with suspected disease based on readily available clinical items and D-dimer concentrations.
Methods and Results: An individual patient data meta-analysis was performed based on sixteen cross-sectional or prospective studies with data from 28 305 adult patients with clinically suspected PE from various clinical settings, including primary care, emergency care, hospitalized and nursing home patients. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict objectively confirmed PE at baseline or venous thromboembolism (VTE) during follow-up of 30 to 90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value <0.10. Discrimination (c-statistic with 95% confidence intervals [CI] and prediction intervals [PI]) and calibration (outcome:expected [O:E] ratio and calibration plot) were evaluated based on internal-external cross-validation. The accuracy of the model was subsequently compared with algorithms based on the Wells score and D-dimer testing. The final model included age (in years), sex, previous VTE, recent surgery or immobilization, haemoptysis, cancer, clinical signs of deep vein thrombosis, inpatient status, D-dimer (in µg/L), and an interaction term between age and D-dimer. The pooled c-statistic was 0.87 (95% CI, 0.85-0.89; 95% PI, 0.77-0.93) and overall calibration was very good (pooled O:E ratio, 0.99; 95% CI, 0.87-1.14; 95% PI, 0.55-1.79). The model slightly overestimated VTE probability in the lower range of estimated probabilities. Discrimination of the current model in the validation data sets was better than that of the Wells score combined with a D-dimer threshold based on age (c-statistic 0.73; 95% CI, 0.70-0.75) or structured clinical pretest probability (c-statistic 0.79; 95% CI, 0.76-0.81).
Conclusion: The present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study.
Registration: PROSPERO ID 89366.
(© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Nuclear receptor subfamily 2 group F member 2 (NR2F2 or COUP-TF2) encodes a transcription factor which is expressed at high levels during mammalian development. Rare heterozygous Mendelian variants in NR2F2 were initially identified in individuals with congenital heart disease (CHD), then subsequently in cohorts of congenital diaphragmatic hernia (CDH) and 46,XX ovotesticular disorders/differences of sexual development (DSD); however, the phenotypic spectrum associated with pathogenic variants in NR2F2 remains poorly characterized. Currently, less than 40 individuals with heterozygous pathogenic variants in NR2F2 have been reported. Here, we review the clinical and molecular details of 17 previously unreported individuals with rare heterozygous NR2F2 variants, the majority of which were de novo. Clinical features were variable, including intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, and vascular malformations, thus expanding the phenotypic spectrum associated with NR2F2 variants. The variants seen were predicted loss of function, including a nonsense variant inherited from a mildly affected mosaic mother, missense and a large deletion including the NR2F2 gene. Our study presents evidence for rare, heterozygous NR2F2 variants causing a highly variable syndrome of congenital anomalies, commonly associated with heart defects, developmental delays/intellectual disability, dysmorphic features, feeding difficulties, hypotonia, and genital anomalies. Based on the new and previous cases, we provide clinical recommendations for evaluating individuals diagnosed with an NR2F2-associated disorder.
(© 2023. The Author(s), under exclusive licence to European Society of Human Genetics.)

FARS2 encodes the mitochondrial phenylalanyl-tRNA synthetase (mtPheRS), which is essential for charging mitochondrial (mt-) tRNA Phe with phenylalanine for use in intramitochondrial translation. Many biallelic, pathogenic FARS2 variants have been described previously, which are mostly associated with two distinct clinical phenotypes; an early onset epileptic mitochondrial encephalomyopathy or a later onset spastic paraplegia. In this study, we report on a patient who presented at 3 weeks of age with tachypnoea and poor feeding, which progressed to severe metabolic decompensation with lactic acidosis and seizure activity followed by death at 9 weeks of age. Rapid trio whole exome sequencing identified compound heterozygous FARS2 variants including a pathogenic exon 2 deletion on one allele and a rare missense variant (c.593G > T, p.(Arg198Leu)) on the other allele, necessitating further work to aid variant classification. Assessment of patient fibroblasts demonstrated severely decreased steady-state levels of mtPheRS, but no obvious defect in any components of the oxidative phosphorylation system. To investigate the potential pathogenicity of the missense variant, we determined its high-resolution crystal structure, demonstrating a local structural destabilization in the catalytic domain. Moreover, the R198L mutation reduced the thermal stability and impaired the enzymatic activity of mtPheRS due to a lower binding affinity for tRNA Phe and a slower turnover rate. Together these data confirm the pathogenicity of this FARS2 variant in causing early-onset mitochondrial epilepsy.
Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose.
(Copyright © 2023 Elsevier Inc. All rights reserved.)

Humans, Mice, Animals, Obesity metabolism, Myeloid Cells metabolism, Stress, Physiological, and Non-alcoholic Fatty Liver Disease metabolism

Although multiple populations of macrophages have been described in the human liver, their function and turnover in patients with obesity at high risk of developing non-alcoholic fatty liver disease (NAFLD) and cirrhosis are currently unknown. Herein, we identify a specific human population of resident liver myeloid cells that protects against the metabolic impairment associated with obesity. By studying the turnover of liver myeloid cells in individuals undergoing liver transplantation, we find that liver myeloid cell turnover differs between humans and mice. Using single-cell techniques and flow cytometry, we determine that the proportion of the protective resident liver myeloid cells, denoted liver myeloid cells 2 (LM2), decreases during obesity. Functional validation approaches using human 2D and 3D cultures reveal that the presence of LM2 ameliorates the oxidative stress associated with obese conditions. Our study indicates that resident myeloid cells could be a therapeutic target to decrease the oxidative stress associated with NAFLD.
(© 2023. The Author(s).)

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]