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Gay and bisexual men (GBM) engaging in chemsex can face various health and well-being-related challenges, the extent of which remains unknown given the limited research in the context of the COVID-19 pandemic. This paper examines the pandemic impacts on the health needs of GBM who engaged in chemsex and their experiences with related services. We applied interpretive description to produce knowledge with direct implications for improving practices and policies. Data were collected between July 2020 and January 2021 using in-depth semi-structured interviews with eight key informants who held chemsex expertise and 13 GBM with chemsex lived experiences. Interviews were transcribed, anonymized, and analyzed thematically, yielding three interrelated themes. First, participants argued that the COVID-19 public health response was heteronormative and moralizing, reinforcing feelings of shame among GBM who engaged in chemsex and further isolating them. This added a layer of stigma and exposed them to increased drug-related risks by obstructing harm reduction practices. Second, participants contended how the pandemic worsened the scarcity and shortcomings of chemsex-specialized services. The mandatory shift to online services made it harder to form meaningful therapeutic relationships, especially given the unique sensitivity and stigma associated with chemsex, further heightened during the pandemic. Third, this online shift simultaneously facilitated access to personalized and culturally sensitive care, especially for those with less urgent needs. Our findings' implications emphasize the importance of adopting a comprehensive approach in chemsex care, integrating both in-person and online methods, to counteract health iniquities reinforced by the pandemic and the institutional responses to it., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Hepatitis C virus (HCV) disproportionately affects certain sub-populations, including people with experience of incarceration (PWEI). Little is known about how perceptions of HCV and treatment have changed despite simplifications in testing and treatment in carceral settings. Nineteen semi-structured interviews were conducted with people living with or having a history of HCV infection released from Quebec provincial prison. Interviews were guided by the Common Sense Self-Regulation Model (CS-SRM) and aimed to explore cognitive and emotional representations of HCV and coping strategies. Among the 19 participants, seven (37%) were diagnosed with HCV in prison and 14 (74%) had previously received HCV treatment. Participants' HCV illness perceptions were influenced by fear (of HCV transmission, death, and the well-being of family) and stigma (related to HCV, injection drug use, and incarceration). While some sought education and social and professional support, others self-isolated or engaged in high-risk behaviors to cope. Despite advances in HCV treatment, PWEI continue to experience various forms of stigma and fear surrounding their HCV diagnosis, resulting in delayed HCV care. These findings provide insights into how prison-based healthcare providers can better utilize HCV illness perceptions to evaluate willingness to engage in HCV care among PWEI.

The efficient importation of quantified gene expression data is pivotal in transcriptomics. Historically, the R package Tximport addressed this need by enabling seamless data integration from various quantification tools. However, the Python community lacked a corresponding tool, restricting cross-platform bioinformatics interoperability. We introduce Pymportx, a Python adaptation of Tximport, which replicates and extends the original package's functionalities. Pymportx maintains the integrity and accuracy of gene expression data while improving processing speed and integration within the Python ecosystem. It supports new data formats and includes tools for enhanced data exploration and analysis. Available under the MIT license, Pymportx integrates smoothly with Python's bioinformatics tools, facilitating a unified and efficient workflow across the R and Python ecosystems. This advancement not only broadens access to Python's extensive toolset but also fosters interdisciplinary collaboration and the development of cutting-edge bioinformatics analyses., (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

Space division multiplexing (SDM) systems using few-mode fibers (FMF) are essential for next-generation fiber optic communications. Optical amplifiers with low noise, minimal differential modal gain (DMG), and minimal differential spectral gain (DSG) are essential for these systems. In this work, we present a method to design and optimize a two-stage few-mode erbium-doped fiber amplifier (FM-EDFA) using a joint DMG-DSG minimization approach. This methodology involves the pumping profile design and the gain flattening filter design. Simulation results show the two-stage FM-EDFA achieves DMG and DSG below 2.8 dB and 0.42 dB, respectively, with an optical signal-to-noise ratio above 19 dB across the C-band, enabling a system capacity of 48.6 Tbps. This work reveals the effectiveness of this two-stage FM-EDFA for optical amplification in the context of SDM systems.

Background: Patient navigation increases linkage to hepatitis C virus (HCV) care following release from prison; however, little is known about the services patient navigators should provide to maximize linkage to care. We aimed to identify perceived barriers and facilitators to linkage to HCV care post-release, and to determine patient navigator services and characteristics best suited to address barriers to linkage to care among people released from prison., Methods: Ten semi-structured interviews were conducted with adult (age ≥18 years) men living with chronic HCV, released from the largest Quebec provincial prison, and linked to HCV care by a patient navigator. Interviews were guided by the Socio-Ecological Model (SEM) and aimed to explore the multi-level barriers and facilitators to linkage to HCV care post-release. Interviews were audio-recorded, transcribed, and analyzed using a deductive, thematic approach., Results: The median age of participants was 54 years. Barriers to linkage to HCV care included competing priorities post-release (e.g., substance use, mental health issues, unstable housing), stigma (related to HCV, injection drug use, and incarceration), and lack of transportation. Facilitators included social support, established relationships with existing healthcare providers, prior cure with direct-acting antivirals, and HCV-related health literacy and knowledge. Perceived essential patient navigator services to enhance linkage included pre-release discharge appointments, housing assistance, and facilitated transportation to HCV appointments. Ensuring a consistent, non-judgemental, and empathetic patient navigator were considered important characteristics; lived experiences of incarceration and/or HCV were not felt to be essential for a patient navigator., Conclusions: Interventions that seek to improve linkage to HCV care for people following release from prison should address many levels (individual, interpersonal, and policy) of the SEM. While people experience several competing priorities post-release, having an empathetic and consistent patient navigator, regardless of their lived experiences of HCV and/or incarceration, may improve linkage to HCV care post-release., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AM, LR, DOP, CD, SC, LdB, AP, ML, and AH report no competing interests. NK reports grants for investigator-initiated studies from ViiV Healthcare, Abbvie, and Gilead, advisory fees from Gilead Sciences, ViiV Healthcare, Merck, and Abbvie, and speaker fees from Gilead Sciences, Abbvie, and Merck, all outside this work. GS has acted as speaker for Merck, Gilead, Abbvie, Novo Nordisk, Pfizer, served as an advisory board member for Pfizer, Merck, Novo Nordisk, Gilead, and has received unrestricted research funding from Theratecnologies Inc. MBK reports grants for investigator-initiated studies from ViiV Healthcare, AbbVie, Merck and Gilead, and consulting fees from ViiV Healthcare, AbbVie and Gilead, all outside the submitted work. BL has received consultancy fees and/or honoraria and research funds from Gilead, ViiV Healthcare, and Merck. JC has received research funding from ViiV Healthcare, Merck, and Gielead, consulting fees from ViiV Healthcare and Gilead, and payment for lectures from Gilead, all outside this work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

In North America, LGBTQ+ youth have high rates of cannabis use and face mental health issues. We conducted a photovoice study to describe the perspectives, needs, and motivations of forty-six LGBTQ+ youth who use cannabis as they access mental healthcare services. Participants' photographs were discussed in individual semi-structured interviews conducted by peer researchers. Following a thematic analysis of the interview transcripts, we first found that, beyond medication, LGBTQ+ youth sought mental health services facilitating introspection to better understand their sexual and gender identities and mental health. Second, participants sought affirming health professionals but often felt judged by providers. Third, access to desired services was often described as uncertain and taxing, which impacted their mental health. Fourth, participants' agency was determined by their experience with mental health services, which translated into resilience to tackle access challenges and cannabis use to mitigate their mental health struggles. Our findings point to the need for mental healthcare delivery that goes beyond medication provision but which in addition foster therapeutic processes based on a holistic understanding of mental health. A trusting dynamic between health professionals and LGBTQ+ youth is imperative to counteract the feelings of stigma experienced by LGBTQ+ youth using cannabis in Canada.

Background: Health care utilization is higher in individuals with multiple sclerosis (MS) than in the general population. However, there are limited data on the reasons for their hospital admissions. Our primary objective is to analyze the reasons for the hospitalization of individuals with MS with the goal of identifying preventable causes., Methods: We conducted a retrospective analysis of a cohort of adults with a confirmed diagnosis of MS admitted to Duke University Hospital between January 2018 and January 2020. This yielded a cohort of 210 individuals. Data were analyzed using descriptive statistics., Results: The most common reason for admission was urinary tract infection (UTI; 10.3%). The average length of stay was 6.1 days for the individuals with MS vs 5.5 days for the general population. The 30-day readmission rates were 14.9% and 15.5%, respectively. A significant number of admitted patients were not on any disease-modifying therapy (DMT), and no difference in median age was identified between those with a DMT vs those without., Conclusions: Length of stay and readmission rates were similar to those of the general population in this contemporary cohort. Given the prevalence of bladder dysfunction in MS, it is not surprising that a UTI was the most common reason for admission. Actively addressing management of and techniques for bladder dysfunction may decrease the admission rate for individuals with MS. Though we now have more treatment options for MS, many individuals with the highest health care utilization are not on a DMT. Future research is needed to identify the factors that can be addressed to support these patients and reduce preventable hospitalizations., (© 2024 Consortium of Multiple Sclerosis Centers.)

Optic neuritis (ON) can present as the first demyelinating attack in both multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), which may require different treatment depending on the final diagnosis. We present 2 young Hispanic women who presented with ON during pregnancy, one of whom was diagnosed with MS and the other with MOGAD. We describe key clinical features to help differentiate between MS and MOGAD including ON features, brain and spinal MRI, CSF profiles, and serum MOG and aquaporin-4 (AQP-4) antibodies, which all can help guide clinicians to an ultimate diagnosis. Pregnancy is usually considered an immunotolerant state because complex immunologic shifts arising to support tolerance of the developing fetus seem to decrease the risk of relapses. However, relapses may still occur during pregnancy, and relapse rates increase immediately postpartum. Our cases raise the possibility that young Hispanic patients may face increased risk of demyelinating disease activity even during the relatively immunotolerant state of pregnancy. A high index of suspicion for demyelinating disease should be maintained to accelerate diagnosis and prevent disability.

Delirium is an acute decline or fluctuation in attention, awareness, or other cognitive function that can lead to serious adverse outcomes. Despite the severe outcomes, delirium is frequently unrecognized and uncoded in patients' electronic health records (EHRs) due to its transient and diverse nature. Natural language processing (NLP), a key technology that extracts medical concepts from clinical narratives, has shown great potential in studies of delirium outcomes and symptoms. To assist in the diagnosis and phenotyping of delirium, we formed an expert panel to categorize diverse delirium symptoms, composed annotation guidelines, created a delirium corpus with diverse delirium symptoms, and developed NLP methods to extract delirium symptoms from clinical notes. We compared 5 state-of-the-art transformer models including 2 models (BERT and RoBERTa) from the general domain and 3 models (BERT_MIMIC, RoBERTa_MIMIC, and GatorTron) from the clinical domain. GatorTron achieved the best strict and lenient F1 scores of 0.8055 and 0.8759, respectively. We conducted an error analysis to identify challenges in annotating delirium symptoms and developing NLP systems. To the best of our knowledge, this is the first large language model-based delirium symptom extraction system. Our study lays the foundation for the future development of computable phenotypes and diagnosis methods for delirium.

Background: Organophosphate, pyrethroid, and neonicotinoid insecticides have resulted in adrenal and gonadal hormone disruption in animal and in vitro studies; limited epidemiologic evidence exists in humans. We assessed relationships of urinary insecticide metabolite concentrations with adrenal and gonadal hormones in adolescents living in Ecuadorean agricultural communities., Methods: In 2016, we examined 522 Ecuadorian adolescents (11-17y, 50.7% female, 22% Indigenous; ESPINA study). We measured urinary insecticide metabolites, blood acetylcholinesterase activity (AChE), and salivary testosterone, dehydroepiandrosterone (DHEA), 17β-estradiol, and cortisol. We used general linear models to assess linear (β = % hormone difference per 50% increase of metabolite concentration) and curvilinear relationships (β 2  = hormone difference per unit increase in squared ln-metabolite) between ln-metabolite or AChE and ln-hormone concentrations, stratified by sex, adjusting for anthropometric, demographic, and awakening response variables. Bayesian Kernel Machine Regression was used to assess non-linear associations and interactions., Results: The organophosphate metabolite malathion dicarboxylic acid (MDA) had positive associations with testosterone (β boys  = 5.88% [1.21%, 10.78%], β girls  = 4.10% [-0.02%, 8.39%]), and cortisol (β boys  = 6.06 [-0.23%, 12.75%]. Para-nitrophenol (organophosphate) had negatively-trending curvilinear associations, with testosterone (β 2 boys  = -0.17 (-0.33, -0.003), p = 0.04) and DHEA (β 2 boys  = -0.49 (-0.80, -0.19), p = 0.001) in boys. The neonicotinoid summary score (β boys  = 5.60% [0.14%, 11.36%]) and the neonicotinoid acetamiprid-N-desmethyl (β boys  = 3.90% [1.28%, 6.58%]) were positively associated with 17β-estradiol, measured in boys only. No associations between the pyrethroid 3-phenoxybenzoic acid and hormones were observed. In girls, bivariate response associations identified interactions of MDA, Para-nitrophenol, and 3,5,6-trichloro-2-pyridinol (organophosphates) with testosterone and DHEA concentrations. In boys, we observed an interaction of MDA and Para-nitrophenol with DHEA. No associations were identified for AChE., Conclusions: We observed evidence of endocrine disruption for specific organophosphate and neonicotinoid metabolite exposures in adolescents. Urinary organophosphate metabolites were associated with testosterone and DHEA concentrations, with stronger associations in boys than girls. Urinary neonicotinoids were positively associated with 17β-estradiol. Longitudinal repeat-measures analyses would be beneficial for causal inference., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Research-based education at the undergraduate level is ideal for fostering the training of future scientists. In an undergraduate Developmental Biology course, this learning strategy requires the availability of model species and enough research reagents, not only for technique training but also for the development of student original projects. This might be challenging in most countries, where resources are limited. Hence, there is a need to develop low-cost solutions for use in the classroom. In this study, we describe the optimization and use of two low-cost protocols in zebrafish embryos for hands-on practical sessions and project-based learning in a Developmental Biology undergraduate course in Ecuador. These protocols were designed for the practical and experimental learning of vertebrate meroblastic cleavage, gastrulation, and neural crest differentiation. The proposed protocols have been previously described in the literature and use silver nitrate and alcian blue, two relatively inexpensive reagents, to label cell membranes and cartilage. The silver nitrate protocol allows the study of cell contact formation during cleavage and the identification of cellular changes during gastrulation, including yolk internalization and epiboly. The alcian blue staining allows the analysis of cranial mesenchymal differentiation into cartilage. These protocols are ideal for practical sessions due to their ease of application, quick results, adaptability to the class schedule, and robustness in the hands of beginning researchers. Finally, these protocols are adaptable for research-based class projects.

Purpose: Empathy is an important construct in patient-physician relationships, particularly critical in family physicians' daily practice. We aimed to understand how empathy has been conceived and integrated into family medicine postgraduate training., Materials and Methods: Medline, PsyINFO, and Embase were searched in this systematic mixed studies systematic review. Two independent reviewers screened abstracts and full texts. Disagreements were solved through research team consensus-based discussion. Included studies were synthesized thematically., Results: A total of 18 studies were included. Four themes were identified. (1) Empathy definition. Included studies stressed the cognitive component of empathy, paired either with a behavioural or an affective response. (2) Empathy modifiers. Starting residency right after medical school, having a role model, having high empathy levels before residency, having children, being married, and being exposed to patient involvement in education were found to have a positive impact on empathy. (3) Empathy-burnout relationship. Whereas greater burnout was related to lower empathy levels, excess empathy seems to favour burnout through 'compassion fatigue.' (4) Educational programs for empathy development. Five programs were identified: a communication workshop, a patient-led program, a mindfulness program, a family-oriented intervention, and an arts-based program., Conclusions: Studies mostly measured the cognitive component of empathy. The moral component of empathy was underrepresented in the conceptualization of empathy and the development of educational interventions. Conflicting evidence exists regarding the decline of empathy levels during the family medicine residency. Longitudinal designs should be privileged when exploring the evolution of empathy levels across the continuum of medical education.

Base excision repair (BER) generates gapped DNA intermediates containing a 5'-terminal 2-deoxyribose-5-phosphate (5'-dRP) group. In mammalian cells, gap filling and dRP removal are catalyzed by Pol β, which belongs to the X family of DNA polymerases. In higher plants, the only member of the X family of DNA polymerases is Pol λ. Although it is generally believed that plant Pol λ participates in BER, there is limited experimental evidence for this hypothesis. Here we have characterized the biochemical properties of Arabidopsis thaliana Pol λ (AtPol λ) in a BER context, using a variety of DNA repair intermediates. We have found that AtPol λ performs gap filling inserting the correct nucleotide, and that the rate of nucleotide incorporation is higher in substrates containing a C in the template strand. Gap filling catalyzed by AtPol λ is most efficient with a phosphate at the 5'-end of the gap and is not inhibited by the presence of a 5'-dRP mimic. We also show that AtPol λ possesses an intrinsic dRP lyase activity that is reduced by mutations at two lysine residues in its 8-kDa domain, one of which is present in Pol λ exclusively and not in any Pol β homolog. Importantly, we also found that the dRP lyase activity of AtPol λ allows efficient completion of uracil repair in a reconstituted short-patch BER reaction. These results suggest that AtPol λ plays an important role in plant BER., (© 2024. The Author(s).)

The ultrasound characteristics of thyroid nodules guide the evaluation of thyroid cancer in patients with thyroid nodules. However, the characteristics of thyroid nodules are often documented in clinical narratives such as ultrasound reports. Previous studies have examined natural language processing (NLP) methods in extracting a limited number of characteristics (<9) using rule-based NLP systems. In this study, a multidisciplinary team of NLP experts and thyroid specialists, identified thyroid nodule characteristics that are important for clinical care, composed annotation guidelines, developed a corpus, and compared 5 state-of-the-art transformer-based NLP methods, including BERT, RoBERTa, LongFormer, DeBERTa, and GatorTron, for extraction of thyroid nodule characteristics from ultrasound reports. Our GatorTron model, a transformer-based large language model trained using over 90 billion words of text, achieved the best strict and lenient F1-score of 0.8851 and 0.9495 for the extraction of a total number of 16 thyroid nodule characteristics, and 0.9321 for linking characteristics to nodules, outperforming other clinical transformer models. To the best of our knowledge, this is the first study to systematically categorize and apply transformer-based NLP models to extract a large number of clinical relevant thyroid nodule characteristics from ultrasound reports. This study lays ground for assessing the documentation quality of thyroid ultrasound reports and examining outcomes of patients with thyroid nodules using electronic health records., (©2023 AMIA - All rights reserved.)

Background: Analysis of circulating tumor DNA (ctDNA) is increasingly used for clinical decision-making in oncology. However, ctDNA could represent ≤ 0.1 % of cell-free DNA in early-stage tumors and its detection requires high-sensitive techniques such as digital PCR (dPCR)., Methods: In 46 samples from patients with early-stage breast cancer, we compared two leading dPCR assays for ctDNA analysis: QX200 droplet digital PCR (ddPCR) system from Bio-Rad which is the gold-standard in the field, and Absolute Q plate-based digital PCR (pdPCR) system from Thermo Fisher Scientific which has not been reported before. We analyzed 5 mL of baseline plasma samples prior to any treatment., Results: Both systems displayed a comparable sensitivity with no significant differences observed in mutant allele frequency. In fact, ddPCR and pdPCR possessed a concordance > 90 % in ctDNA positivity. Nevertheless, ddPCR exhibited higher variability and a longer workflow. Finally, we explored the association between ctDNA levels and clinicopathological features. Significantly higher ctDNA levels were present in patients with a Ki67 score > 20 % or with estrogen receptor-negative or triple-negative breast cancer subtypes., Conclusion: Both ddPCR and pdPCR may constitute sensitive and reliable tools for ctDNA analysis with an adequate agreement in early-stage breast cancer patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Haematuria is a common complication in prostate cancer patients receiving anticoagulation for venous thromboembolism (VTE). Early identification of at-risk patients might help to reduce its incidence and severity., Methods: We used data from the RIETE registry to develop a prognostic score for haematuria during the first year of anticoagulation for VTE. The prognostic score was built using regression coefficients., Results: From March 2001 through March 2021, 1934 patients with prostate cancer and acute VTE were enrolled. Of these, 1034 (53 %) initially presented as pulmonary embolism and 900 (47 %) as isolated deep vein thrombosis (DVT). During anticoagulation (median 181 days; inter-quartile range: 97-354), 99 patients (5.1 %) developed haematuria (fatal 1, major 27, non-major 72). The incidence rate was: 8 events per 100 patient-years (95%CI 6.5-9.7). Median time to haematuria was 53 days (IQR 4-134). On multivariable analysis, recent haematuria, initial presentation as DVT, comorbidity, metastases, haemoglobin levels <11 g/dL, creatinine >1.2 mg/dL, and radiotherapy independently predicted the risk for haematuria. C-statistics was 0.71 (95%CI: 0.65-0.77). A cut-off of ≥1.5 points classified 312 patients (20 %) at high-risk and had the highest sensitivity (51 %; 95%CI: 39-62) and specificity (82 %; 95%CI: 79-83). Our score improved the performance and non-event net reclassification index (NRI) of the RIETE score (c-statistics: 0.61; 95%CI: 0.54-0.68; NRI: 0.09) or VTE-BLEED score (c-statistics: 0.64; 95%CI: 0.58-0.71; NRI: 0.76)., Conclusions: A prognostic score for haematuria during anticoagulation for VTE performed well in patients with prostate cancer, and improved identification compared to other validated scores., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aims: This study aimed to examine antibiotic resistance and the epidemiology of extended-spectrum β-lactamases (ESBL)-producing Escherichia coli associated with bloodstream infections over a period of 10 years., Methods and Results: Isolates were collected from January 2009 to December 2019 and those testing for E. coli were included. Antibiotic susceptibility was tested using the VITEK® system. Selected isolates were further characterized by amplification of marker genes (virulence traits, phylogroups, and sequence types). A total of 166 ESBL-producing E. coli were recovered. The blaCTX-M-15 allele was the most abundant. Most of the isolates were resistant to ceftriaxone, cefepime, ceftazidime, ampicillin/sulbactam, piperacillin/tazobactam, and ciprofloxacin. No resistance to carbapenems was registered. More than 80% of bacteria were classified as extraintestinal pathogenic E. coli (ExPEC), and the combination of virulence traits:papA-papC-kpsMII-uitA was the most common. Phylogroup B2 was the most prevalent, and bacteria predominantly belonged to ST131., Conclusions: There was an increase in the ExPEC ESBL-E coli in bloodstream infections and the relationship between the isolates found in these infections during these 10 years., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Habitat conversion and climate change are fundamental drivers of biodiversity loss worldwide but are often analyzed in isolation. We used a continental-scale, decades-long database of more than 150,000 bird nesting attempts to explore how extreme heat affects avian reproduction in forests, grasslands, and agricultural and developed areas across the US. We found that in forests, extreme heat increased nest success, but birds nesting in agricultural settings were much less likely to successfully fledge young when temperatures reached anomalously high levels. Species that build exposed cup nests and species of higher conservation concern were particularly vulnerable to maximum temperature anomalies in agricultural settings. Finally, future projections suggested that ongoing climate change may exacerbate the negative effects of habitat conversion on avian nesting success, thereby compromising conservation efforts in human-dominated landscapes.

Background: The spread of antibiotic-resistant bacteria may be driven by human-animal-environment interactions, especially in regions with limited restrictions on antibiotic use, widespread food animal production, and free-roaming domestic animals. In this study, we aimed to identify risk factors related to commercial food animal production, small-scale or "backyard" food animal production, domestic animal ownership, and practices related to animal handling, waste disposal, and antibiotic use in Ecuadorian communities., Methods and Findings: We conducted a repeated measures study from 2018 to 2021 in 7 semirural parishes of Quito, Ecuador to identify determinants of third-generation cephalosporin-resistant E. coli (3GCR-EC) and extended-spectrum beta-lactamase E. coli (ESBL-EC) in children. We collected 1,699 fecal samples from 600 children and 1,871 domestic animal fecal samples from 376 of the same households at up to 5 time points per household over the 3-year study period. We used multivariable log-binomial regression models to estimate relative risks (RR) of 3GCR-EC and ESBL-EC carriage, adjusting for child sex and age, caregiver education, household wealth, and recent child antibiotic use. Risk factors for 3GCR-EC included living within 5 km of more than 5 commercial food animal operations (RR: 1.26; 95% confidence interval (CI): 1.10, 1.45; p-value: 0.001), household pig ownership (RR: 1.23; 95% CI: 1.02, 1.48; p-value: 0.030) and child pet contact (RR: 1.23; 95% CI: 1.09, 1.39; p-value: 0.001). Risk factors for ESBL-EC were dog ownership (RR: 1.35; 95% CI: 1.00, 1.83; p-value: 0.053), child pet contact (RR: 1.54; 95% CI: 1.10, 2.16; p-value: 0.012), and placing animal feces on household land/crops (RR: 1.63; 95% CI: 1.09, 2.46; p-value: 0.019). The primary limitations of this study are the use of proxy and self-reported exposure measures and the use of a single beta-lactamase drug (ceftazidime with clavulanic acid) in combination disk diffusion tests for ESBL confirmation, potentially underestimating phenotypic ESBL production among cephalosporin-resistant E. coli isolates. To improve ESBL determination, it is recommended to use 2 combination disk diffusion tests (ceftazidime with clavulanic acid and cefotaxime with clavulanic acid) for ESBL confirmatory testing. Future studies should also characterize transmission pathways by assessing antibiotic resistance in commercial food animals and environmental reservoirs., Conclusions: In this study, we observed an increase in enteric colonization of antibiotic-resistant bacteria among children with exposures to domestic animals and their waste in the household environment and children living in areas with a higher density of commercial food animal production operations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Amato et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Herbicides are the most used class of pesticides worldwide, and insect repellents are widely used globally. Yet, there is a dearth of studies characterizing the associations between these chemical groups and human neurobehavior. Experimental studies suggest that glyphosate and 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides can affect neurobehavior and the cholinergic and glutamatergic pathways in the brain. We aim to assess whether herbicides and insect repellents are associated with neurobehavioral performance in adolescents., Methods: We assessed 519 participants (11-17 years of age) living in agricultural communities in Ecuador. We quantified urinary concentrations of glyphosate, 2,4-D, and two N,N-diethyl-meta-toluamide (DEET) insect repellent metabolites [3-(diethylcarbamoyl)benzoic acid (DCBA) and 3-(ethylcarbamoyl)benzoic acid (ECBA)] using isotope-dilution mass spectrometry. We assessed neurobehavioral performance using 9 subtests across 5 domains (attention/inhibitory control, memory/learning, language, visuospatial processing, and social perception). We characterized the associations using generalized estimating equations and multiple imputation for metabolites below detection limits. Models were adjusted for demographic and anthropometric characteristics, urinary creatinine, and sexual maturation. Mediation by salivary cortisol, dehydroepiandrosterone, 17 β -estradiol , and testosterone was assessed using structural equation modeling., Results: The mean of each neurobehavioral domain score was between 7.0 and 8.7 [standard deviation (SD) range: 2.0-2.3]. Glyphosate was detected in 98.3% of participants, 2,4-D in 66.2%, DCBA in 63.3%, and ECBA in 33.4%. 2,4-D was negatively associated with all neurobehavioral domains, but statistically significant associations were observed with attention/inhibition [score difference per 50% higher metabolite concentration ( β ) = - 0.19 95% confidence interval (CI): - 0.31 , - 0.07 ], language [ β = - 0.12 (95% CI: - 0.23 , - 0.01 )], and memory/learning [ β = - 0.11 (95% CI: - 0.22 , 0.01)]. Glyphosate had a statistically significant negative association only with social perception [ β = - 0.08 (95% CI: - 0.14 , - 0.01 )]. DEET metabolites were not associated with neurobehavioral performance. Mediation by gender and adrenal hormones was not observed., Conclusion: This study describes worse neurobehavioral performance associated with herbicide exposures in adolescents, particularly with 2,4-D. Replication of these findings among other pediatric and adult populations is needed. https://doi.org/10.1289/EHP11383.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The coronavirus 2019 (COVID-19) pandemic has had significant impacts on health systems, population dynamics, public health awareness, and antibiotic stewardship, which could affect antibiotic resistant bacteria (ARB) emergence and transmission. In this study, we aimed to compare knowledge, attitudes, and practices (KAP) of antibiotic use and ARB carriage in Ecuadorian communities before versus after the COVID-19 pandemic began. We leveraged data collected for a repeated measures observational study of third-generation cephalosporin-resistant E. coli (3GCR-EC) carriage among children in semi-rural communities in Quito, Ecuador between July 2018 and September 2021. We included 241 households that participated in surveys and child stool sample collection in 2019, before the pandemic, and in 2021, after the pandemic began. We estimated adjusted Prevalence Ratios (aPR) and 95% Confidence Intervals (CI) using logistic and Poisson regression models. Child antibiotic use in the last 3 months declined from 17% pre-pandemic to 5% in 2021 (aPR: 0.30; 95% CI 0.15, 0.61) and 3GCR-EC carriage among children declined from 40 to 23% (aPR: 0.48; 95% CI 0.32, 0.73). Multi-drug resistance declined from 86 to 70% (aPR: 0.32; 95% CI 0.13; 0.79), the average number of antibiotic resistance genes (ARGs) per 3GCR-EC isolate declined from 9.9 to 7.8 (aPR of 0.79; 95% CI 0.65, 0.96), and the diversity of ARGs was lower in 2021. In the context of Ecuador, where COVID-19 prevention and control measures were strictly enforced after its major cities experienced some of the world's the highest mortality rates from SARS-CoV-2 infections, antibiotic use and ARB carriage declined in semi-rural communities of Quito from 2019 to 2021., (© 2023. Springer Nature Limited.)

Background: Posttraumatic stress disorder is characterized by deficits in cognitive flexibility related to dysfunction of the medial prefrontal cortex (mPFC). Exposure therapy can effectively reverse these deficits. Fear extinction in rodents bears similarity to exposure therapy. Extinction reverses chronic stress-induced deficits in cognitive flexibility on the attentional set-shifting test (AST), an mPFC-mediated process. This therapeutic effect requires activity of pyramidal neurons and brain derived neurotrophic factor (BDNF) signaling in infralimbic cortex (IL). However, the circuit mechanisms governing BDNF-mediated plasticity initiated by extinction in IL are unknown. The ventral hippocampus (vHipp) plays a role in regulating IL activity during extinction, and plasticity in vHipp is necessary for extinction memory consolidation. Therefore, we investigated the role of vHipp input to IL in the effects of extinction in reversing stress-induced cognitive deficits., Methods: vHipp input to IL was silenced using a Gi-Designer Receptors Exclusively Activated by Designer Drugs (DREADD) via local infusion of clozapine-N-oxide (CNO) into IL before extinction. A day later, rats were tested on AST. In a separate experiment, we tested whether vHipp input to the IL induces BDNF signaling to exert therapeutic effects. We activated the vHipp using a Gq-DREADD, and injected an anti-BDNF neutralizing antibody into IL. Rats were tested on the AST 24 hours later., Results: Silencing the vHipp input to IL prevented the beneficial effects of extinction in reversing stress-induced cognitive deficits. Activating vHipp input to IL in the absence of extinction was sufficient to reverse stress-induced deficits in set-shifting. The beneficial effects were blocked by local infusion of a neutralizing anti-BDNF antibody into IL., Conclusions: vHipp-driven BDNF signaling in IL is critical for extinction to counteract the deleterious cognitive effects of chronic stress., (© The Author(s) 2023. Published by Oxford University Press on behalf of CINP.)

The European Society of Organ Transplantation (ESOT) strives to promote equity, diversity, and inclusion (EDI) across all its activities. We surveyed the transplant community's experiences and perspectives regarding EDI within ESOT as an organization and its educational activities, and research in general. A total of 299 respondents completed the questionnaire. About half agreed that ESOT's Executive Committee, Council, and Sections/Committees are diverse and inclusive (51%) and that ESOT promotes EDI in its live and digital educational activities (54%). Forty percent of respondents agreed that scientific and clinical trials in the field of transplantation are diverse and inclusive. Despite the wide distribution of the survey, most of the respondents self-identified as White and were either physician or surgeon. However, the results contribute a unique insight into the experiences and perspectives of the transplantation community regarding EDI. Whilst ESOT is committed to the principles of EDI, perceptions and the high number of proposals show the apparent need to prioritize efforts to embed EDI across ESOT and transplantation science. These data should constitute a starting point for change and provide guidance for future efforts to promote EDI within the transplantation community., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pengel, Kaisar, Benjamens, Ibrahim, Ricci, Bellini, Breithaupt-Faloppa, Falk, Maple, Marson, Ortiz, Papalois, Paredes and Forsberg.)

Urban sustainability and sustainable mobility have become the central focus of sustainable development initiatives. The city of 15 models seeks to ensure that urban development is sustainable. This paper evaluates the current state of mobility and the use of sustainable transport in the specific context of the city of Antofagasta, which, due to its characteristics of urban expansion and its mining activity, has been considered an international reference case. In particular, we study how the current urban structure shapes the city's travel patterns and identify opportunities for public policy actions to focus their investment and urban intervention efforts on the essential aspects that make it possible to achieve 15- or 20-min territories. The results reveal the need for urban development initiatives to focus on improving the supply of goods and services in areas with low installed capacity, promoting the culture of micro-neighbourhoods, and encouraging cycling. In particular, only 10% of trips, for all purposes and all modes of transport, are completed in less than 15 min. And about 58% of trips, for all purposes and all modes, are completed in less than 30 min. In the marginal effects of the multinomial logit model, a one-unit increase in travel time increases the probability of choosing to travel by public transport by 63% and decreases the probability of walking by 41%., (© 2023. The New York Academy of Medicine.)

Apples are the third most produced fruit in the world, but their production is often pesticide-intensive. Our objective was to identify options for pesticide reduction using farmer records from 2549 commercial apple fields in Austria during five years between 2010 and 2016. Using generalized additive mixed modeling, we examined how pesticide use was related to farm management, apple varieties, and meteorological parameters, and how it affected yields and toxicity to honeybees. Apple fields received 29.5 ± 8.6 (mean ± SD) pesticide applications per season at a rate of 56.7 ± 22.7 kg ha -1 , which included a total of 228 pesticide products with 80 active ingredients. Over the years, fungicides accounted for 71 % of the pesticide amounts applied, insecticides for 15 %, and herbicides for 8 %. The most frequently used fungicides were sulfur (52 %), followed by captan (16 %) and dithianon (11 %). Of insecticides, paraffin oil (75 %) and chlorpyrifos/chlorpyrifos-methyl (6 % combined) were most frequently used. Among herbicides, glyphosate (54 %), CPA (20 %) and pendimethalin (12 %) were most often used. Pesticide use increased with increasing frequency of tillage and fertilization, increasing field size, increasing spring temperatures, and drier summer conditions. Pesticide use decreased with increasing number of summer days with maximum temperatures >30 °C and number of warm, humid days. Apple yields were significantly positively related to the number of heat days, warm humid nights, and pesticide treatment frequency, but were not affected by frequency of fertilization and tillage. Honeybee toxicity was not related to insecticide use. Pesticide use and yield were significantly related to apple varieties. Our analysis shows that pesticide use in the apple farms studied can be reduced by less fertilization and tillage, partly because yields were >50 % higher than the European average. However, weather extremes related to climate change, such as drier summers, could challenge plans to reduce pesticide use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Deep brain stimulation (DBS) is commonly used to alleviate motor symptoms in several movement disorders. However, the procedure is invasive, and the technology has remained largely stagnant since its inception decades ago. Recently, we have shown that wireless nanoelectrodes may offer an alternative approach to conventional DBS. However, this method is still in its infancy, and more research is required to characterize its potential before it can be considered as an alternative to conventional DBS., Objectives: Herein, we aimed to investigate the effect of stimulation via magnetoelectric nanoelectrodes on primary neurotransmitter systems that have implications for DBS in movement disorders., Methods: Mice were injected with either magnetoelectric nanoparticles (MENPs) or magnetostrictive nanoparticles (MSNPs, as a control) in the subthalamic nucleus (STN). Mice then underwent magnetic stimulation, and their motor behavior was assessed in the open field test. In addition, magnetic stimulation was applied before sacrifice and post-mortem brains were processed for immunohistochemistry (IHC) to assess the co-expression of c-Fos with either tyrosine hydroxylase (TH), tryptophan hydroxylase-2 (TPH2) or choline acetyltransferase (ChAT)., Results: Stimulated animals covered longer distances in the open field test when compared to controls. Moreover, we found a significant increase in c-Fos expression in the motor cortex (MC) and paraventricular region of the thalamus (PV-thalamus) after magnetoelectric stimulation. Stimulated animals showed fewer TPH2/c-Fos double-labeled cells in the dorsal raphe nucleus (DRN), as well as TH/c-Fos double-labeled cells in the ventral tegmental area (VTA), but not in the substantia nigra pars compacta (SNc). There was no significant difference in the number of ChAT/ c-Fos double-labeled cells in the pedunculopontine nucleus (PPN)., Conclusions: Magnetoelectric DBS in mice enables selective modulation of deep brain areas and animal behavior. The measured behavioral responses are associated with changes in relevant neurotransmitter systems. These changes are somewhat similar to those observed in conventional DBS, suggesting that magnetoelectric DBS might be a suitable alternative., Competing Interests: Conflict of interest All authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

There are no studies reporting the effects of Salmonella enterica subsp. enterica serovar Infantis ( S . Infantis) on intestinal architecture and immunoglobulin serum levels in chickens. Here, we measured these parameters and hypothesized whether probiotic administration could modulate the observed outcomes. Two-hundred 1-day-old COBB 500 male chicks were allocated into four groups: (I) the control, (II) the group treated with L. fermentum , (III) the group exposed to S . Infantis, and (IV) the group inoculated with both bacteria. At 11 days post infection, blood was gathered from animals which were then euthanized, and samples from the small intestine were collected. Intestinal conditions, as well as IgA and IgM serum levels, were assessed. S . Infantis reduced villus-height-to-crypt-depth (VH:CD) ratios in duodenal, jejunal, and ileal sections compared to control conditions, although no differences were found regarding the number of goblet cells, muc-2 expression, and immunoglobulin concentration. L. fermentum improved intestinal measurements compared to the control; this effect was also evidenced in birds infected with S . Infantis. IgM serum levels augmented in response to the probiotic in infected animals. Certainly, the application of L. fermentum elicited positive outcomes in S . Infantis-challenged chickens and thus must be considered for developing novel treatments designed to reduce unwanted infections.

Background: Many people living with HIV struggle to consistently adhere to antiretroviral therapy, fail to achieve long-term virologic control and remain at risk for HIV-related disease progression, development of resistance and may transmit HIV infection to others., Objective: To determine if switching from current multi-tablet (curART) to single-tablet antiretroviral therapy (abacavir/lamivudine/dolutegravir; ABC/3TC/DTG), both combined with individualized adherence support, would improve HIV suppression in non-adherent vulnerable populations., Methods: TriiADD was an investigator-initiated randomized, multicentre, open label study. HIV+ adults with documented non-adherence on curART were randomized in a 1:1 ratio to immediately switch to ABC/3TC/DTG or to continue curART. Both arms received adherence support. The primary outcome was the proportion of participants in each arm with HIV RNA < 50 copies/mL 24 weeks after randomization., Results: In total, 50 people were screened and 27 randomized from 11 sites across Canada before the trial was stopped early due to slow recruitment. Participants were predominantly from ethnocultural communities, Indigenous people and/or had a history of injection drug use. The proportion achieving HIV RNA < 50 copies/mL at week 24 was 4/12 (33%) in the curART arm vs 7/13 (54%) in the ABC/3TC/DTG arm; median Bayesian risk difference, 5% (95% CrI, -17 to 28%) higher for those randomized to ABC/3TC/DTG. We encountered difficulties with recruitment of participants without prior drug resistance, retention despite intensive support, reliably measuring adherence and in overcoming entrenched adherence barriers., Conclusion: Results of our trial are consistent with a slight improvement in viral suppression in a vulnerable population when a single tablet regimen is combined with patient-level adherence support. Beyond treatment simplicity and tolerability, tailored interventions addressing stigma and social determinants of health are still needed. The numerous challenges we encountered illustrate how randomised trials may not be the best approach for assessing adherence interventions in vulnerable populations., Competing Interests: M.B.K. has received research support and consulting fees from ViiV Healthcare, AbbVie and Gilead. S.W. has received grants, consulting fees, lecture fees, nonfinancial support, and fees for the development of educational presentations from ViiV Health Care, GSK, Merck, Janssen, and Gilead Sciences. A.W. received consulting fees and honoraria from Merck, Gilead, ViiV Healthcare, and AbbVie. V.M.-L. has received research support from Gilead and Merck and consulting fees from AbbVie. N.P. has received honoraria from Gilead and ViiV Healthcare. B.C. is a board member, consultant, and has received grants and payment for lectures from AbbVie, Gilead, and Merck, and payment for educational presentations from AbbVie. J.A. serves on Advisory Boards for Gilead and ViiV and has performed contract research and other work for Gilead, ViiV and Merck. J.-G.B. has received consulting fees from Gilead Sciences, Merck, ViiV Healthcare, grants from Gilead Sciences, Merck, ViiV Healthcare, and payment for lectures from Gilead Sciences, Merck, ViiV Healthcare. C.F. has received grants from AbbVie, Gilead Sciences, Merck, and ViiV Healthcare. B.L. has received for investigator-initiated studies from ViiV Healthcare, Merck, and Gilead; consulting fees from ViiV Healthcare, Merck, and Gilead. He is the holder of a Canadian Institutes for Health Research, Strategy for Patient-Oriented Research Mentorship Chair in Innovative Clinical Trials for HIV Care. D.H.S.T. has received investigator-initiated research grants from AbbVie, Gilead Sciences inc. and ViiV Healthcare. D.H.S.T. is a Site Principal Investigator for clinical trials sponsored by Glaxo Smith Kline. Also, D.H.S.T. reports grants, personal fees from Canadian Institutes of Health Research, grants from Canada Research Chairs, grants from CIHR Canadian HIV Trials Network, during the conduct of the study. S.T. reports grants from GSK, outside the submitted work. The authors report no other conflicts of interest to declare., (© 2022 Klein et al.)

This Guide for Living Donor Kidney Transplantation (LDKT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this Guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes. Moreover, the role of living donors in the current KT context should recover the level of importance it had until recently. To this end the new forms of incompatible HLA and/or ABO donation, as well as the paired donation which is possible in several hospitals with experience in LDKT, offer additional ways to treat renal patients with an incompatible donor. Good results in terms of patient and graft survival have expanded the range of circumstances under which living renal donors are accepted. Older donors are now accepted, as are others with factors that affect the decision, such as a borderline clinical history or alterations, which when evaluated may lead to an additional number of transplantations. This Guide does not forget that LDKT may lead to risk for the donor. Pre-donation evaluation has to centre on the problems which may arise over the short or long-term, and these have to be described to the potential donor so that they are able take them into account. Experience over recent years has led to progress in risk analysis, to protect donors' health. This aspect always has to be taken into account by LDKT programmes when evaluating potential donors. Finally, this Guide has been designed to aid decision-making, with recommendations and suggestions when uncertainties arise in pre-donation studies. Its overarching aim is to ensure that informed consent is based on high quality studies and information supplied to donors and recipients, offering the strongest possible guarantees., (Copyright © 2022. Published by Elsevier España, S.L.U.)

Significant evolutionary shifts in locomotor behaviour often involve comparatively subtle anatomical transitions. For dinosaurian and avian evolution, medial overhang of the proximal femur has been central to discussions. However, there is an apparent conflict with regard to the evolutionary origin of the dinosaurian femoral head, with neontological and palaeontological data suggesting seemingly incongruent hypotheses. To reconcile this, we reconstructed the evolutionary history of morphogenesis of the proximal end of the femur from early archosaurs to crown birds. Embryological comparison of living archosaurs (crocodylians and birds) suggests the acquisition of the greater overhang of the femoral head in dinosaurs results from additional growth of the proximal end in the medial-ward direction. On the other hand, the fossil record suggests that this overhang was acquired by torsion of the proximal end, which projected in a more rostral direction ancestrally. We reconcile this apparent conflict by inferring that the medial overhang of the dinosaur femoral head was initially acquired by torsion, which was then superseded by mediad growth. Details of anatomical shifts in fossil forms support this hypothesis, and their biomechanical implications are congruent with the general consensus regarding broader morpho-functional evolution on the avian stem.

The more restrictive regulations of pesticides in Europe have led to an increase in conservation biological control (CBC) research. However, little attention has been paid to the main determinants of Lobesia botrana parasitism. The Douro Demarcated Region landscape offers scope for the use of CBC. The study was conducted between 2002 and 2015 aiming at: (i) identifying parasitoids associated with L. botrana and evaluating their impact as biological control agents in each generation of the pest, and (ii) evaluating the effect of both the proportion of ecological infrastructures (EI) near the vineyards, and the impact of management practices (chemical treatments and ground cover) on the parasitism of L. botrana . A total of 3226 larvae/pupae of L. botrana were collected (15% were parasitized and 485 parasitoids emerged). A complex of 16 taxa of parasitoids was identified, the majority belonging to Hymenoptera. The most abundant were Elachertus sp. (Eulophidae), Campoplex capitator Aubert (Ichneumonidae), and Brachymeria tibialis (Walker) (Chalcididae), which represented 62.5, 12.6, and 12.0% of the total assemblage of parasitoids which emerged, respectively. The percentage of parasitism ranged from 0.0 to 61.5% (first generation), from 0.0 to 36.8% (second generation), and from 0.0 to 12.1% (third generation). Importantly, it was found that the parasitism rate was higher in vineyards with ground cover. In addition, EI in the area surrounding the vineyards produced a significant increase in parasitism. These results suggest potential for CBC of L. botrana if EI around vineyards, and ground cover with native perennial plants within vineyards, are encouraged.

Increasing diversity on farms can enhance many key ecosystem services to and from agriculture, and natural control of arthropod pests is often presumed to be among them. The expectation that increasing the size of monocultural crop plantings exacerbates the impact of pests is common throughout the agroecological literature. However, the theoretical basis for this expectation is uncertain; mechanistic mathematical models suggest instead that increasing field size can have positive, negative, neutral, or even nonlinear effects on arthropod pest densities. Here, we report a broad survey of crop field-size effects: across 14 pest species, 5 crops, and 20,000 field years of observations, we quantify the impact of field size on pest densities, pesticide applications, and crop yield. We find no evidence that larger fields cause consistently worse pest impacts. The most common outcome (9 of 14 species) was for pest severity to be independent of field size; larger fields resulted in less severe pest problems for four species, and only one species exhibited the expected trend of larger fields worsening pest severity. Importantly, pest responses to field size strongly correlated with their responses to the fraction of the surrounding landscape planted to the focal crop, suggesting that shared ecological processes produce parallel responses to crop simplification across spatial scales. We conclude that the idea that larger field sizes consistently disrupt natural pest control services is without foundation in either the theoretical or empirical record.

Salmonella enterica serovars cause infections in humans. S. enterica subsp. enterica serovar Infantis is considered relevant and is commonly reported in poultry products. Evaluating innovative approaches for resisting colonization in animals could contribute to the goal of reducing potential human infections. Microalgae represent a source of molecules associated with performance and health improvement in chickens. Tetraselmis chuii synthesizes fermentable polysaccharides as part of their cell wall content; these sugars are known for influencing caecal bacterial diversity. We hypothesized if its dietary administration could exert a positive effect on caecal microbiota in favor of a reduced S. Infantis load. A total of 72 one-day-old broiler chickens (COBB 500) were randomly allocated into three groups: a control, a group infected with bacteria (day 4), and a group challenged with S. Infantis but fed a microalgae-based diet. Caecal samples ( n = 8) were collected two days post-infection. A PMAxx TM -based qPCR approach was developed to assess differences regarding bacterial viable load between groups. The inclusion of the microalga did not modify S. Infantis content, although the assay proved to be efficient, sensitive, and repeatable. The utilized scheme could serve as a foundation for developing novel PCR-based methodologies for estimating Salmonella colonization.

Living birds (Aves) have bodies substantially modified from the ancestral reptilian condition. The avian pelvis in particular experienced major changes during the transition from early archosaurs to living birds 1,2 . This stepwise transformation is well documented by an excellent fossil record 2-4 ; however, the ontogenetic alterations that underly it are less well understood. We used embryological imaging techniques to examine the morphogenesis of avian pelvic tissues in three dimensions, allowing direct comparison with the fossil record. Many ancestral dinosaurian features 2 (for example, a forward-facing pubis, short ilium and pubic 'boot') are transiently present in the early morphogenesis of birds and arrive at their typical 'avian' form after transitioning through a prenatal developmental sequence that mirrors the phylogenetic sequence of character acquisition. We demonstrate quantitatively that avian pelvic ontogeny parallels the non-avian dinosaur-to-bird transition and provide evidence for phenotypic covariance within the pelvis that is conserved across Archosauria. The presence of ancestral states in avian embryos may stem from this conserved covariant relationship. In sum, our data provide evidence that the avian pelvis, whose early development has been little studied 5-7 , evolved through terminal addition-a mechanism 8-10 whereby new apomorphic states are added to the end of a developmental sequence, resulting in expression 8,11 of ancestral character states earlier in that sequence. The phenotypic integration we detected suggests a previously unrecognized mechanism for terminal addition and hints that retention of ancestral states in development is common during evolutionary transitions., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Phenomenon: Clinical teachers perform overlapping tasks in education and patient care. They are therefore expected to juggle many professional identities such as educator and clinician. Yet little is known about how clinical teachers negotiate their professional identities. The present research examined the lived experiences of clinical teachers as they manage and make sense of their professional identities in the context of a faculty development program., Approach: This study adopted interpretative phenomenological analysis, which is an idiographic and inductive methodological approach that enables an in-depth examination of how people conceptualize their personal and social worlds. In-depth semi-structured individual interviews were conducted with six purposively sampled Brazilian clinical teachers who were attending a faculty development program. Each participant's lived experience was analyzed independently. Then, these individual analyses were compared against each other to identify convergence and divergence., Findings: Participants recognized one identity, which was labeled as embedding identity , containing other identities and roles. Participants integrated their professional identities in agreement with their personal identities, values, and beliefs, striving thus for identity consonance. Participants understood their craft as a relational process by which they wove themselves into their context and entangled their experience with that of others. They, however, diverged when recognizing who their peers were; whereas some named a single professional group (i.e., family physicians), others had a more comprehensive view and considered as peers healthcare professionals, students, and even patients. Finally, participants identified time constraints and lower prestige of family medicine as a medical discipline vis-à-vis other specialties as challenges posed by their contexts., Insights: Clinical teachers have multifaceted identities, to which they give a sense, manage, and integrate into their daily practice. Participants recognized an embedding identity and looked for common points between the identities it contained, which allowed them to meaningfully reconcile the different demands from their overlapping professional identities. Thus, this research introduces the notion of embedding identity as a strategy to make sense of many professional identities. Variability in the embedding identities depicted in this investigation suggests the fluid and contextualized character of professional identity development. How participants saw themselves also influenced how they behaved and interacted with others accordingly. Understanding clinical teacher identity development enriches current perspectives of what it is like to be one of these medical professionals. Faculty development programs ought to consider these perspectives to better support clinical teachers in meeting the overlapping demands in education and patient care.

Post-traumatic stress disorder (PTSD) is a debilitating illness characterized by dysfunction in the medial prefrontal cortex (mPFC). Although both pharmacological and cognitive behavioral interventions have shown some promise at alleviating symptoms, high attrition and persistence of treatment-resistant symptoms pose significant challenges that remain unresolved. Specifically, prolonged exposure therapy, a gold standard intervention to treat PTSD, has high dropout rates resulting in many patients receiving less than a fully effective course of treatment. Administering pharmacological treatments together with behavioral psychotherapies like prolonged exposure may offer an important avenue for enhancing therapeutic efficacy sooner, thus reducing the duration of treatment and mitigating the impact of attrition. In this study, using extinction learning as a rat model of exposure therapy, we hypothesized that administering ketamine as an adjunct treatment together with extinction will enhance the efficacy of extinction in reversing stress-induced deficits in set shifting, a measure of cognitive flexibility. Results showed that combining a sub-effective dose of ketamine with a shortened, sub-effective extinction protocol fully reversed stress-induced cognitive set-shifting deficits in both male and female rats. These effects may be due to shared molecular mechanisms between extinction and ketamine, such as increased neuronal plasticity in common circuitry (e.g., hippocampus-mPFC), or increased BDNF signaling. This work suggests that fast-acting drugs, such as ketamine, can be effectively used in combination with behavioral interventions to reduce treatment duration and potentially mitigate the impact of attrition. Future work is needed to delineate other pharmacotherapies that may complement the effects of extinction via shared or independent mechanisms., Competing Interests: Dr. Paredes, Mrs. Knippenberg, Dr. Bulin and Mrs. Keppler have no competing interests. Dr. Morilak receives in-kind research support from 10.13039/501100013327Lundbeck that has no relation to the work presented in this paper., (© 2022 The Authors.)

Variability in population densities is key to the ecology of natural systems but also has great implications for agriculture. Farmers' decisions are heavily influenced by their risk aversion to pest outbreaks that result in major yield losses. However, the need for long-term pest population data across many farms has prevented researchers from exploring the drivers and implications of pest population variability (PV). Here, we demonstrate the critical importance of PV for sustainable farming by analyzing 13 years of pest densities across >1300 Spanish olive groves and vineyards. Variable populations were more likely to cause major yield losses, but also occasionally created temporal windows when densities fell below insecticide spray thresholds. Importantly, environmental factors regulating pest variability were very distinct from factors regulating mean density, suggesting variability needs to be uniquely managed. Finally, we found diversifying landscapes may be a win-win situation for conservation and farmers, as diversified landscapes promote less abundant and less variable pest populations. Therefore, we encourage agricultural stakeholders to increase the complexity of the landscapes surrounding their farms through conserving/restoring natural habitat and/or diversifying crops., (© 2022 The Ecological Society of America.)

Background: Direct-acting antiviral (DAA) uptake is challenging across HIV-hepatitis C (HCV) coinfected populations. This study sought to identify barriers and facilitators related to DAA uptake in priority populations in Canada., Methods: This qualitative descriptive study included 11 people living with HIV with a history of HCV and 15 HCV care providers. Participants were part of either nominal groups (n = 4) or individual interviews (n = 6) in which they identified and ranked barriers and facilitators to DAA uptake. Consolidated lists of barriers and facilitators were identified thematically., Results: Patient participants highly ranked the following barriers: competing priorities and needs (ie, social instability and mental health), delays in care, lack of adherence, and polypharmacy. Provider participant top barriers were the following: competing priorities and needs (ie, social chaos), delays in care (eg, systemic barriers, difficulties engaging patients, lack of trained HCV providers), and HCV-related stigma. Patient participants identified having a strong network of health care providers, family, and friends, possessing intrinsic motivation, and DAAs being a simple and tolerable oral treatment as important facilitators. Provider participant top-ranked facilitators were having resources to identify hard-to-reach populations (eg, patient navigation, outreach), holistic care and addiction management, provider HCV education, and a strong network of interprofessional collaboration., Conclusion: The barriers to DAA initiation addressed by patients and providers overlapped, with some nuances. Multidisciplinary care fostering a strong supportive network and intrinsically motivated patients along with HCV education emerged as key facilitators. This study provides insights for developing potential strategies to improve DAA uptake among HIV-HCV coinfected people in Canada., Competing Interests: MB Klein reports grants from Gilead, during the conduct of the study; grants from ViiV Healthcare, grants from Merck, grants from AbbVie, outside the submitted work. B Lebouché reports grants for investigator-initiated studies from ViiV Healthcare, Merck, and Gilead; consulting fees from ViiV Healthcare, Merck, and Gilead. He is the holder of a Canadian Institutes for Health Research, Strategy for Patient-Oriented Research Mentorship Chair in Innovative Clinical Trials for HIV Care and is also supported by a career award, LE 250, from the Quebec’s Ministry of Health for researchers in Family Medicine. The other authors have nothing to disclose., (Copyright © 2022 Canadian Association for the Study of the Liver.)

Background: Organophosphates are insecticides that inhibit the enzymatic activity of acetylcholinesterase (AChE). Because of this, AChE is considered a physiological marker of organophosphate exposure in agricultural settings. However, limited research exists on the associations between urinary organophosphate metabolites and AChE activity in children., Methods: This study included 526 participants from 2 exams (April and July-October 2016) of ages 12-17 years living in agricultural communities in Ecuador. AChE activity was measured at both examinations, and organophosphate metabolites, including para-nitrophenol (PNP), 3,5,6-trichloro-2-pyridinol (TCPy), and malathion dicarboxylic acid (MDA) were measured in urine collected in July-October. We used generalized estimating equation generalized linear model (GEEGLM), adjusting for hemoglobin, creatinine, and other demographic and anthropometric covariates, to estimate associations of urinary metabolite concentrations with AChE activity (July-October) and AChE% change between April and July-October., Results: The mean (SD) of AChE and AChE% change (April vs July-October) were 3.67 U/mL (0.54) and -2.5% (15.4%), respectively. AChE activity was inversely associated with PNP concentration, whereas AChE% change was inversely associated with PNP and MDA. There was evidence of a threshold: difference was only significant above the 80th percentile of PNP concentration (AChE difference per SD increase of metabolite = -0.12 U/mL [95%CI: 0.20, -0.04]). Likewise, associations with AChE% change were significant only above the 80th percentile of TCPy (AChE % change per SD increase of metabolite = -1.38% [95%CI: 2.43%, -0.32%]) and PNP -2.47% [95%CI: 4.45%, -0.50%]). PNP concentration at ≥80th percentile was associated with elevated ORs for low AChE activity of 2.9 (95% CI: 1.5, 5.7) and for AChE inhibition of ≤ -10% of 3.7 (95% CI: 1.4, 9.8)., Conclusions: Urinary organophosphate metabolites, including PNP, TCPy and MDA, particularly at concentrations above the 80th percentile, were associated with lower AChE activity among adolescents. These findings bring attention to the value of using multiple constructs of pesticide exposure in epidemiologic studies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Limb muscles are remarkably complex and evolutionarily labile. Although their anatomy is of great interest for studies of the evolution of form and function, their homologies among major amniote clades have remained obscure. Studies of adult musculature are inconclusive owing to the highly derived morphology of modern amniote limbs but correspondences become increasingly evident earlier in ontogeny. We followed the embryonic development of forelimb musculature in representatives of six major amniote clades and found, contrary to current consensus, that these early splitting patterns are highly conserved across Amniota. Muscle mass cleavage patterns and topology are highly conserved in reptiles including birds, irrespective of their skeletal modifications: the avian flight apparatus results from slight early topological modifications that are exaggerated during ontogeny. Therian mammals, while conservative in their cleavage patterns, depart drastically from the ancestral amniote musculoskeletal organization in terms of topology. These topological changes occur through extension, translocation and displacement of muscle groups later in development. Overall, the simplicity underlying the apparent complexity of forelimb muscle development allows us to resolve conflicting hypotheses about homology and to trace the history of each individual forelimb muscle throughout the amniote radiations., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)