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Food security is a commonly screened for health-related social need at hospitals and community settings, and until recently, there were no tools to additionally screen for nutrition security. The purpose of this study was to assess the potential advantage of including a one-item brief nutrition security screener (BNSS) alongside the commonly used two-item Hunger Vital Sign (HVS) food security screener for identifying individuals with diet-related health risks. Cross-sectional survey data were collected from April to June 2021. Generalized linear mixed models were used to assess associations between screening status and dietary and health variables. Recruitment was done across five states (California, Florida, Maryland, North Carolina, and Washington) from community-based organizations. Participants (n = 435) were, on average, 44.7 years old (SD = 14.5), predominantly women (77%), and racially/ethnically diverse. In adjusted analyses, being in the food insecure and nutrition insecure group (but not the food insecure and nutrition secure or food secure and nutrition insecure groups) was associated with significantly increased odds for self-reported "fair" or "poor" general health [OR = 2.914 (95% CI = 1.521–5.581)], reporting at least one chronic condition [2.028 (1.024–4.018)], and "low" fruit and vegetable intake [2.421 (1.258–4.660)], compared with the food secure and nutrition secure group. These findings support using both the HVS and BNSS simultaneously in health-related social needs screening to identify participants at the highest risk for poor dietary and health outcomes and warrant further investigation into applying these screeners to clinical and community settings. [ABSTRACT FROM AUTHOR]

Understanding the links between different phases of outflows from active galactic nuclei is a key goal in extragalactic astrophysics. Here, we compare [O  iii ]  |$\lambda \lambda$| 4960, 5008 outflow signatures in quasars with and without broad absorption lines (BALs), aiming to test how the broad absorption troughs seen in the rest-frame ultraviolet are linked to the narrow line region outflows seen in the rest-frame optical. We present new near-infrared spectra from Magellan/FIRE that cover [O  iii ] in 12 quasars with |$2.1\lt z\lt 2.3$|⁠ , selected to have strong outflow signatures in C  iv |$\lambda$| 1550. Combining with data from the literature, we build a sample of 73 BAL, 115 miniBAL, and 125 non-BAL quasars with |$1.5\lt z\lt 2.6$|⁠. The strength and velocity width of [O  iii ] correlate strongly with the C  iv emission properties, but no significant difference is seen in the [O  iii ] emission-line properties between the BALs, non-BALs, and miniBALs once the dependence on C  iv emission is taken into account. A weak correlation is observed between the velocities of C  iv BALs and [O  iii ] emission, which is accounted for by the fact that both outflow signatures correlate with the underlying C  iv emission properties. Our results add to the growing evidence that BALs and non-BALs are drawn from the same parent population and are consistent with a scenario wherein BAL troughs are intermittent tracers of persistent quasar outflows, with a part of such outflow becoming optically thick along our line of sight for sporadic periods of time within which BALs are observed. [ABSTRACT FROM AUTHOR]

With wider availability of synthetic and semi-synthetic cannabinoids in the consumer space, there is a growing impact on public health and safety. Forensic toxicology laboratories should keep these compounds in mind as they attempt to remain effective in screening for potential sources of human performance impairment. Enzyme-linked immunosorbent assay (ELISA) is a commonly utilized tool in forensic toxicology, as its efficiency and sensitivity make it useful for rapid and easy screening for a large number of drugs. This screening technique has lower specificity, which allows for broad cross-reactivity among structurally similar compounds. In this study, the Cannabinoids Direct ELISA kit from Immunalysis was utilized to assess the cross-reactivities of 24 cannabinoids and metabolites in whole blood. The assay was calibrated with 5 ng/mL of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol and the analytes of interest were evaluated at concentrations ranging from 5 to 500 ng/mL. Most parent compounds demonstrated cross-reactivity ≥20 ng/mL, with increasing alkyl side-chain length relative to Δ9-tetrahydrocannabinol resulting in decreased cross-reactivity. Of the 24 analytes, only the carboxylic acid metabolites, 11-nor-9-carboxy-Δ8-tetrahydrocannabinol, 11-nor-9(R)-carboxy-hexahydrocannabinol and 11-nor-9(S)-carboxy-hexahydrocannabinol, were cross-reactive at levels ≤10 ng/mL. Interestingly, 11-nor-9(R)-carboxy-hexahydrocannabinol demonstrated cross-reactivity at 5 ng/mL, where its stereoisomer 11-nor-9(S)-carboxy-hexahydrocannabinol, did not. As more information emerges about the prevalence of these analytes in blood specimens, it is important to understand and characterize their impact on current testing paradigms. [ABSTRACT FROM AUTHOR]

Herbicides are commonly used in forestry to enhance conifer tree growth by reducing the abundance of competitive, undesired, early successional species. Reducing the abundance of understory species could also lead to changes in community composition that need to be documented to aid the understanding of any downstream ecosystem changes. We examined the effects of glyphosate-based herbicides on the abundance, diversity, and community composition of the understory vegetation community of forests located in the temperate-boreal transition zone. We sampled 37 blocks in two ecoregions of the Acadian Forest in eastern Canada that were harvested over the last 15 years. Species richness, Shannon's diversity, or evenness did not differ among blocks with different herbicide history. However, community composition differed between the non-herbicide and herbicide blocks in both ecoregions. Overall, 26.5% of the plant community variation was explained by the factors herbicide use (10.6%), Biomass Growth Index/site quality (8.6%), time since harvest (3.6%), and ecoregion (1.7%). We found 16 indicator species that differentiated the non-herbicide (9 species) and herbicide blocks (7 species). Indicator species for non-herbicide blocks included two blueberry species, three shrubs (two flowering), and two ferns, whereas indicator species for herbicide blocks were largely perennial forbs. Together, our results indicate that herbicide use does not alter species richness but does reduce shrub abundance, a change that persists throughout the 10 years post-herbicide application captured in our study. The reduced shrub layer likely leads to other changes in the plant community. Herbicide use is associated with subtle changes to the understory plant community, and these changes are missed when only alpha diversity is used to examine the effects of herbicides use on community composition. [ABSTRACT FROM AUTHOR]

This article describes a genome assembly and annotation for Bombus dahlbomii , the giant Patagonian bumble bee. DNA from a single, haploid male collected in Argentina was used for PacBio (HiFi) sequencing, and Hi-C technology was then used to map chromatin contacts. Using Juicer and manual curation, the genome was scaffolded into 18 main pseudomolecules, representing a high-quality, near chromosome-level assembly. The sequenced genome size is estimated at 265 Mb. The genome was annotated based on RNA sequencing data of another male from Argentina, and BRAKER3 produced 15,767 annotated genes. The genome and annotation show high completeness, with >95% BUSCO scores for both the genome and annotated genes (based on conserved genes from Hymenoptera). This genome provides a valuable resource for studying the biology of this iconic and endangered species, as well as for understanding the impacts of its decline and designing strategies for its preservation. [ABSTRACT FROM AUTHOR]

The article discusses the concept of chemoprotection of the ovary during chemotherapy as a potential strategy for fertility preservation. It highlights the challenges and limitations of current approaches to fertility preservation, such as cryopreservation, and explores the potential benefits of chemoprotection as a complementary strategy. The study by Wu et al. is referenced, which investigates the use of CHEK1/2 inhibitors to protect the ovary during chemotherapy. The article emphasizes the need for further research and validation of chemoprotective agents, as well as the importance of integrating fertility preservation considerations into oncological trials and drug development. [Extracted from the article]

Climate anomalies are increasing and posing strong selection, which can lead to rapid evolution. This is occurring on a backdrop of interannual variability that might weaken or even reverse selection. However, the effect of interannual climatic variability on rapid evolution is rarely considered. We study the climatic differences that contribute to rapid evolution throughout a 7-year period, encompassing a severe drought across 12 populations of Mimulus cardinalis (scarlet monkeyflower). Plants were grown in a common greenhouse environment under wet and dry treatments, where specific leaf area and date of flowering were measured. We examine the association between trait values and different climate metrics at different time periods, including the collection year, prior years, and cumulative metrics across sequential years. Of the climatic variables we assessed, we find that anomalies in mean annual precipitation best describe trait differences over our study period. Past climates, of 1–2 years prior, are often related to trait values in a conflicting direction to collection-year climate. Uncovering these complex climatic impacts on evolution is critical to better predict and interpret the impacts of climate change. [ABSTRACT FROM AUTHOR]

Background Rapid initiation of antiretroviral therapy (rapid ART) improves clinical outcomes in people with HIV and is endorsed by clinical guidelines. However, logistical challenges limit widespread implementation. We describe an innovative rapid ART model led by pharmacists and its impact on clinical outcomes, including time to viral suppression (TVS). Methods On 1 January 2019, we implemented Pharmacist-Driven Rapid ART (PHARM-D RAPID ART), including rapid ART initiation by pharmacists. Our retrospective cohort study compared TVS, using a Cox proportional hazards model, and clinical outcomes among individuals with a new HIV diagnosis before (1 January 2017 to 31 December 2017) and after (1 January 2019 to 31 December 2019) implementation. Results A total of 108 individuals were included. TVS was significantly shorter (P <.001) for the PHARM-D RAPID ART group (n = 51) compared with the preimplementation group (n = 57) (median: 30 days and 66 days, respectively). Those in the PHARM-D RAPID ART group were significantly more likely to achieve VS at any given time during the study period (adjusted hazard ratio: 3.47 [95% confidence interval, 2.25–5.33]). A total of 94.1% (48/51) of patients in the PHARM-D RAPID ART group were retained in care at 1 year. With a median follow-up of 2.4 years in the PHARM-D RAPID ART group, 98% remained suppressed at last recorded viral load. Conclusions A pharmacist-driven model for rapid ART delivery decreases TVS with high rates of retention in care and durable VS. This model could improve clinical outcomes and increase program feasibility and sustainability. [ABSTRACT FROM AUTHOR]

Gene duplication contributes to the evolution of expression and the origin of new genes, but the relative importance of different patterns of duplicate gene expression and mechanisms of retention remains debated and particularly poorly understood in bacteria. Here, we investigated gene expression patterns for two lab strains of the cyanobacterium Acaryochloris marina with expanding genomes that contain about 10-fold more gene duplicates compared with most bacteria. Strikingly, we observed a generally stoichiometric pattern of greater combined duplicate transcript dosage with increased gene copy number, in contrast to the prevalence of expression reduction reported for many eukaryotes. We conclude that increased transcript dosage is likely an important mechanism of initial duplicate retention in these bacteria and may persist over long periods of evolutionary time. However, we also observed that paralog expression can diverge rapidly, including possible functional partitioning, for which different copies were respectively more highly expressed in at least one condition. Divergence may be promoted by the physical separation of most Acaryochloris duplicates on different genetic elements. In addition, expression pattern for ancestrally shared duplicates could differ between strains, emphasizing that duplicate expression fate need not be deterministic. We further observed evidence for context-dependent transcript dosage, where the aggregate expression of duplicates was either greater or lower than their single-copy homolog depending on physiological state. Finally, we illustrate how these different expression patterns of duplicated genes impact Acaryochloris biology for the innovation of a novel light-harvesting apparatus and for the regulation of recA paralogs in response to environmental change. [ABSTRACT FROM AUTHOR]

The origin of radio emission in different populations of radio-quiet quasars is relatively unknown, but recent work has uncovered various drivers of increased radio-detection fraction. In this work, we pull together three known factors: optical colour (g − i), C  iv distance (a proxy for L / L Edd), and whether or not the quasar contains broad absorption lines (BALQSOs) which signify an outflow. We use SDSS (Sloan Digital Sky Survey) DR14 spectra along with the LOFAR Two Metre Sky Survey Data Release 2 and find that each of these properties have an independent effect. BALQSOs are marginally more likely to be radio-detected than non-BALQSOs at similar colours and L / L Edd, moderate reddening significantly increases the radio-detection fraction and the radio detection increases with L / L Edd above a threshold for all populations. We test a widely used simple model for radio wind shock emission and calculate energetic efficiencies that would be required to reproduce the observed radio properties. We discuss interpretations of these results concerning radio-quiet quasars more generally. We suggest that radio emission in BALQSOs is connected to a different physical origin than the general quasar population since they show different radio properties independent of colour and C  iv distance. [ABSTRACT FROM AUTHOR]

Background Emergency department (ED) clinicians are more frequently providing care, including end-of-life care, to older people. Objectives To estimate the need for ED end-of-life care for people aged ≥65 years, describe characteristics of those dying within 48 hours of ED presentation and compare those dying in ED with those dying elsewhere. Methods We conducted a retrospective cohort study analysing data from 177 hospitals in Australia and New Zealand. Data on older people presenting to ED from January to December 2018, and those who died within 48 hours of ED presentation, were analysed using simple descriptive statistics and univariate logistic regression. Results From participating hospitals in Australia or New Zealand, 10,921 deaths in older people occurred. The 48-hour mortality rate was 6.43 per 1,000 ED presentations (95% confidence interval: 6.31–6.56). Just over a quarter (n = 3,067, 28.1%) died in ED. About one-quarter of the cohort (n = 2,887, 26.4%) was triaged into less urgent triage categories. Factors with an increased risk of dying in ED included age 65–74 years, ambulance arrival, most urgent triage categories, principal diagnosis of circulatory system disorder, and not identifying as an Aboriginal or Torres Strait Islander person. Of the 7,677 older people admitted, half (n = 3,836, 50.0%) had an encounter for palliative care prior to, or during, this presentation. Conclusions Our findings provide insight into the challenges of recognising the dying older patient and differentiating those appropriate for end-of-life care. We support recommendations for national advanced care planning registers and suggest a review of triage systems with an older person-focused lens. [ABSTRACT FROM AUTHOR]

Background Multiplex molecular diagnostic panels have greatly enhanced detection of gastrointestinal pathogens. However, data on the impact of these tests on clinical and patient-centered outcomes are limited. Methods We conducted a prospective, multicenter, stepped-wedge trial to determine the impact of multiplex molecular testing at 5 academic children's hospitals on children presenting to the emergency department with acute gastroenteritis. Caregivers were interviewed on enrollment and 7–10 days after enrollment to determine symptoms, risk factors, subsequent medical visits, and impact on family members. During the pre-intervention period, diagnostic testing was performed at the clinician's discretion. During the intervention period, multiplex molecular testing was performed on all children, with results available to clinicians. The primary outcome was return visits to a healthcare provider within 10 days of enrollment. Results Potential pathogens were identified by clinician-ordered tests in 19 of 571 (3.3%) in the pre-intervention period compared with 434 of 586 (74%) in the intervention period; clinically relevant pathogens were detected in 2.1% and 15%, respectively. In the multivariate model, the intervention was associated with a 21% reduction in the odds of any return visit (odds ratio, 0.79; 95% confidence interval,.70–.90) after adjusting for potential confounders. Appropriate treatment was prescribed in 11.3% compared with 19.6% during the intervention period (P =.22). Conclusions Routine molecular multiplex testing for all children who presented to the ED with acute gastroenteritis detected more clinically relevant pathogens and led to a 21% decrease in return visits. Additional research is needed to define patients most likely to benefit from testing. Clinical Trials Registration. NCT02248285. [ABSTRACT FROM AUTHOR]

Keeping abreast of the antimicrobial stewardship–related articles published each year is challenging. The Southeastern Research Group Endeavor identified antimicrobial stewardship–related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation. [ABSTRACT FROM AUTHOR]

The document is a collection of abstracts from the Third AACC Preanalytical Phase Conference, which focused on implementing preanalytical tools to improve patient care in clinical laboratories. The abstracts cover a range of topics, including improved blood collection practices, positive patient identification devices, evaluation of novel collection systems, and the impact of preanalytical errors on laboratory testing. The conference provided an opportunity for the laboratory community to share ideas and research in the field of preanalytics. The abstracts were submitted by speakers from various countries, highlighting the diverse perspectives in this area of study. [Extracted from the article]

Objective We postulated that adalimumab [ADA] drug clearance [CL] may be a more critical determinant of therapeutic outcome than ADA concentration. This was tested in Crohn's disease [CD] patients undergoing ADA maintenance treatment. Methods CD patients from four cohorts received ADA induction and started maintenance therapy. Therapeutic outcomes consisted of endoscopic remission [ER], sustained C-reactive protein [CRP] based clinical remission [defined as CRP levels below 3 mg/L in the absence of symptoms], and faecal calprotectin [FC] level below 100 µg/g. Serum albumin, ADA concentration, and anti-drug antibody status were determined using immunochemistry and homogeneous mobility shift assay, respectively. CL was determined using a nonlinear mixed effect model with Bayesian priors. Statistical analysis consisted of Mann–Whitney test and logistic regression with calculation of odds ratio. Repeated event analysis was conducted using a nonlinear mixed effect model. Results In 237 enrolled patients [median age 40 years, 45% females], median CL was lower in patients achieving ER as compared with those with persistent active endoscopic disease [median 0.247 L/day vs 0.326 L/day, respectively] [ p  <0.01]. There was no significant difference in ADA concentration between patients in endoscopic remission compared with those with recurrence [median 9.3 µg/mL vs 11.7 µg/mL, respectively]. Sustained CRP-based clinical remission and FC levels below 100 µg/g were generally associated with lower CL and higher ADA concentration. Repeated event analysis confirmed those findings with better performances of CL than concentration in associating with ER and other outcomes. Conclusion Lower ADA clearance is associated with an improved clinical outcome for patients with Crohn's disease and may be a superior pharmacokinetic measure than concentration. [ABSTRACT FROM AUTHOR]

Background Real-world evidence of coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) booster effectiveness among patients with immune dysfunction are limited. Methods We included data from patients in the United States National COVID Cohort Collaborative (N3C) who completed ≥2 doses of mRNA vaccination between 10 December 2020 and 27 May 2022. Immune dysfunction conditions included human immunodeficiency virus infection, solid organ or bone marrow transplant, autoimmune diseases, and cancer. We defined incident COVID-19 BTI as positive results from laboratory tests or diagnostic codes 14 days after at least 2 doses of mRNA vaccination; and severe COVID-19 BTI as hospitalization, invasive cardiopulmonary support, and/or death. We used propensity scores to match boosted versus nonboosted patients and evaluated hazards of incident and severe COVID-19 BTI using Cox regression after matching. Results Among patients without immune dysfunction, the relative effectiveness of booster (3 doses) after 6 months from the primary (2 doses) vaccination against BTI ranged from 69% to 81% during the Delta-predominant period and from 33% to 39% during the Omicron-predominant period. Relative effectiveness against BTI was lower among patients with immune dysfunction but remained statistically significant in both periods. Boosted patients had lower risk of COVID-19–related hospitalization (hazard ratios [HR] ranged from 0.5 [95% confidence interval {CI},.48–.53] to 0.63 [95% CI,.56–.70]), invasive cardiopulmonary support, or death (HRs ranged from 0.46 [95% CI,.41–.52] to 0.63 [95% CI,.50–.79]) during both periods. Conclusions Booster vaccines remain effective against severe COVID-19 BTI throughout the Delta- and Omicron-predominant periods, regardless of patients' immune status. [ABSTRACT FROM AUTHOR]

In active galactic nuclei, the relationship between UV and X-ray luminosity is well studied (often characterised by αox) but often with heterogeneous samples. We have parametrized the intrinsic distribution of X-ray luminosity, L X, for the optically selected sample of SDSS quasars in the Stripe 82 and XXL fields across redshifts 0.5–3.5. We make use of the available XMM observations and a custom pipeline to produce Bayesian sensitivity curves that are used to derive the intrinsic X-ray distribution in a hierarchical Bayesian framework. We find that the X-ray luminosity distribution is well described by a Gaussian function in log10  L X space with a mean that is dependent on the monochromatic 2500 Å UV luminosity, L 2500. We also observe some redshift dependence of the distribution. The mean of the L X distribution increases with redshift while the width decreases. This weak but significant redshift dependence leads to L 2500– L X and L 2500–αox relations that evolve with redshift, and we produce a redshift- and L 2500-dependent αox equation. Neither black hole mass nor Eddington ratio appear to be potential drivers of the redshift evolution. [ABSTRACT FROM AUTHOR]

The purpose of the research was to examine challenges women face in policing that may serve as barriers to the recruitment of other women; identifying challenges is crucial for developing strategies that attract women to the profession. The study employed in-depth, qualitative interviews with 16 policewomen. Emergent themes suggest six initiatives that could aid in recruiting more women: (1) Create recruitment materials that highlight roles that are not gender specific; (2) Provide fitness guidance to alleviate fears of inadequacy; (3) Organize mentorships that engage women interested in the profession; (4) Ensure representation of women in leadership roles; (5) Ensure that leaders identify and address inequities immediately to foster belonging; and (6) Institute family-friendly accommodations that allow recruits to balance work and home life. The officers interviewed reported finding purpose in policing, but they recognized the need to attract women in a concerted effort. Nationwide police departments are challenged to recruit women. Creating images, opportunities, and environments that demonstrate appreciation for women in the profession may aid in recruitment. [ABSTRACT FROM AUTHOR]

Human activities are accelerating rates of biological invasions and climate-driven range expansions globally, yet we understand little of how genomic processes facilitate the invasion process. Although most of the literature has focused on underlying phenotypic correlates of invasiveness, advances in genomic technologies are showing a strong link between genomic variation and invasion success. Here, we consider the ability of genomic tools and technologies to (i) inform mechanistic understanding of biological invasions and (ii) solve real-world issues in predicting and managing biological invasions. For both, we examine the current state of the field and discuss how genomics can be leveraged in the future. In addition, we make recommendations pertinent to broader research issues, such as data sovereignty, metadata standards, collaboration, and science communication best practices that will require concerted efforts from the global invasion genomics community. [ABSTRACT FROM AUTHOR]

The Society of Behavioral Medicine (SBM) supports increased funding for policies in the 2024 Farm Bill that align with a Food is Medicine (FIM) framework and address multiple dimensions of human and planetary health. [ABSTRACT FROM AUTHOR]

Blueshifts – or, more accurately, blue asymmetries – in broad emission lines such as C  iv λ1550 are common in luminous quasars and correlate with fundamental properties such as Eddington ratio and broad absorption line (BAL) characteristics. However, the formation of these blueshifts is still not understood, and neither is their physical connection to the BAL phenomenon or accretion disc. In this work, we present Monte Carlo radiative transfer and photoionization simulations using parametrized biconical disc-wind models. We take advantage of the azimuthal symmetry of a quasar and show that we can reproduce C  iv blueshifts provided that (i) the disc-mid-plane is optically thick out to radii beyond the line formation region, so that the receding wind bicone is obscured; and (ii) the system is viewed from relatively low (that is, more face-on) inclinations (≲40°). We show that C  iv emission-line blueshifts and BALs can form in the same wind structure. The velocity profile of the wind has a significant impact on the location of the line formation region and the resulting line profile, suggesting that the shape of the emission lines can be used as a probe of wind-driving physics. While we are successful at producing blueshifts/blue asymmetries in outflows, we struggle to match the detailed shape or skew of the observed emission-line profiles. In addition, our models produce redshifted emission-line asymmetries for certain viewing angles. We discuss our work in the context of the C  iv λ1550 emission blueshift versus equivalent-width space and explore the implications for quasar disc wind physics. [ABSTRACT FROM AUTHOR]

The Heinz C. Prechter Longitudinal Study of Bipolar Disorder is an ongoing research project that collects comprehensive data on individuals with bipolar disorder and other psychiatric illnesses, as well as control participants. The study focuses on long-term outcomes patterns and various aspects of bipolar disorder, including its functional, physical, emotional, molecular, and neurocognitive aspects. The study has incorporated measures to assess the impact of the COVID-19 pandemic on participants and collects data through self-report assessments, mobile technology, and biological samples. The study has a diverse cohort and aims to increase diversity by actively recruiting participants from underrepresented populations. The data from the study is available through the Heinz C. Prechter Genetic Repository. [Extracted from the article]

Functional human brown and white adipose tissue (BAT and WAT) are vital for thermoregulation and nutritional homeostasis, while obesity and other stressors lead, respectively, to cold intolerance and metabolic disease. Understanding BAT and WAT physiology and dysfunction necessitates clinical trials complemented by mechanistic experiments at the cellular level. These require standardized in vitro models, currently lacking, that establish references for gene expression and function. We generated and characterized a pair of immortalized, clonal human brown (hBA) and white (hWA) preadipocytes derived from the perirenal and subcutaneous depots, respectively, of a 40-year-old male individual. Cells were immortalized with hTERT and confirmed to be of a mesenchymal, nonhematopoietic lineage based on fluorescence-activated cell sorting and DNA barcoding. Functional assessments showed that the hWA and hBA phenocopied primary adipocytes in terms of adrenergic signaling, lipolysis, and thermogenesis. Compared to hWA, hBA were metabolically distinct, with higher rates of glucose uptake and lactate metabolism, and greater basal, maximal, and nonmitochondrial respiration, providing a mechanistic explanation for the association between obesity and BAT dysfunction. The hBA also responded to the stress of maximal respiration by using both endogenous and exogenous fatty acids. In contrast to certain mouse models, hBA adrenergic thermogenesis was mediated by several mechanisms, not principally via uncoupling protein 1 (UCP1). Transcriptomics via RNA-seq were consistent with the functional studies and established a molecular signature for each cell type before and after differentiation. These standardized cells are anticipated to become a common resource for future physiological, pharmacological, and genetic studies of human adipocytes. [ABSTRACT FROM AUTHOR]

Research directed at select prototype pathogens is part of the approach put forth by the National Institute of Allergy and Infectious Disease (NIAID) to prepare for future pandemics caused by emerging viruses. We were tasked with identifying suitable prototypes for four virus families of the Bunyavirales order (Phenuiviridae , Peribunyaviridae , Nairoviridae , and Hantaviridae). This is a challenge due to the breadth and diversity of these viral groups. While there are many differences among the Bunyavirales , they generally have complex ecological life cycles, segmented genomes, and cause a range of human clinical outcomes from mild to severe and even death. Here, we delineate potential prototype species that encompass the breadth of clinical outcomes of a given family, have existing reverse genetics tools or animal disease models, and can be amenable to a platform approach to vaccine testing. Suggested prototype pathogens outlined here can serve as a starting point for further discussions. [ABSTRACT FROM AUTHOR]

Understanding whether and how resource limitation alters phenotypic selection on floral traits is key to predict the evolution of plant–pollinator interactions under climate change. Two important resources predicted to decline with our changing climate are pollinators and water in the form of increased droughts. Most work, however, has studied these selective agents separately and in the case of water deficit, studies are rare. Here, we use the common morning glory (Ipomoea purpurea) to investigate the effects of experimental reduction in pollinator access and water availability on floral signals and nectar rewards and their effects on phenotypic selection on these traits. We conducted a manipulative experiment in a common garden, where we grew plants in three treatments: (1) pollinator restriction, (2) water reduction and (3) unmanipulated control. Plants in pollinator restriction and control treatments were well-watered compared to water deficit. We found that in contrast to pollinator restriction, water deficit had strong effects altering floral signals and nectar rewards but also differed in the direction and strength of selection on these traits compared to control plants. Water deficit increased the opportunity for selection, and selection in this treatment favoured lower nectar volumes and larger floral sizes, which might further alter pollinator visitation. In addition, well-watered plants, both in control and pollinator deficit, showed similar patterns of selection to increase nectar volume suggesting non-pollinator-mediated selection on nectar. Our study shows that floral traits may evolve in response to reduction in water access faster than to declines in pollinators and reinforces that abiotic factors can be important agents of selection for floral traits. Although only few experimental selection studies have manipulated access to biotic and abiotic resources, our results suggest that this approach is key for understanding how pollination systems may evolve under climate change. [ABSTRACT FROM AUTHOR]

We analyse the rest-frame ultraviolet (UV) spectra of 2531 high-redshift (3.5 < z < 4.0) quasars from the Sloan Digital Sky Survey DR16Q catalogue. In combination with previous work, we study the redshift evolution of the rest-frame UV line properties across the entire redshift range, 1.5 < z < 4.0. We improve the systemic redshift estimates at z > 3.5 using a cross-correlation algorithm that employs high signal-to-noise template spectra spanning the full range in UV emission line properties. We then quantify the evolution of C  iv and He  ii emission line properties with redshift. The increase in C  iv blueshifts with cosmological redshift can be fully explained by the higher luminosities of quasars observed at high redshifts. We recover broadly similar trends between the He  ii equivalent width and C  iv blueshift at both 1.5 < z < 2.65 and 3.5 < z < 4.0 suggesting that the blueshift depends systematically on the spectral energy density (SED) of the quasar and there is no evolution in the SED over the redshift range 1.5 < z < 4.0. C  iv blueshifts are highest when L / L |$_\text {Edd} \ge$| 0.2 and M bh ≥ 109 M⊙ for the entire 1.5 < z < 4.0 sample. We find that luminosity matching samples as a means to explore the evolution of their rest-frame UV emission line properties is only viable if the samples are also matched in the M bh – L / L |$_\text {Edd}$| plane. Quasars at z ≥ 6 are on average less massive and have higher Eddington-scaled accretion rates than their luminosity-matched counterparts at 1.5 < z < 4.0, which could explain the observed evolution in their UV line properties. [ABSTRACT FROM AUTHOR]

Mother's Curse alleles represent a significant source of potential male fitness defects. The maternal inheritance of mutations with the pattern of sex-specific fitness effects, s ♀ > 0 > s ♂ ⁠ , allows Mother's Curse alleles to spread through a population even though they reduce male fitness. Although the mitochondrial genomes of animals contain only a handful of protein-coding genes, mutations in many of these genes have been shown to have a direct effect on male fertility. The evolutionary process of nuclear compensation is hypothesized to counteract the male-limited mitochondrial defects that spread via Mother's Curse. Here we use population genetic models to investigate the evolution of compensatory autosomal nuclear mutations that act to restore the loss of fitness caused by mitochondrial mutation pressures. We derive the rate of male fitness deterioration by Mother's Curse and the rate of restoration by nuclear compensatory evolution. We find that the rate of nuclear gene compensation is many times slower than that of its deterioration by cytoplasmic mutation pressure, resulting in a significant lag in the recovery of male fitness. Thus, the numbers of nuclear genes capable of restoring male mitochondrial fitness defects must be large in order to sustain male fitness in the face of mutation pressures. [ABSTRACT FROM AUTHOR]

The use of next-generation sequencing technology has enabled phylogenetic studies with hundreds of thousands of taxa. Such large-scale phylogenies have become a critical component in genomic epidemiology in pathogens such as SARS-CoV-2 and influenza A virus. However, detailed phenotypic characterization of pathogens or generating a computationally tractable dataset for detailed phylogenetic analyses requires objective subsampling of taxa. To address this need, we propose parnas , an objective and flexible algorithm to sample and select taxa that best represent observed diversity by solving a generalized k-medoids problem on a phylogenetic tree. parnas solves this problem efficiently and exactly by novel optimizations and adapting algorithms from operations research. For more nuanced selections, taxa can be weighted with metadata or genetic sequence parameters, and the pool of potential representatives can be user-constrained. Motivated by influenza A virus genomic surveillance and vaccine design, parnas can be applied to identify representative taxa that optimally cover the diversity in a phylogeny within a specified distance radius. We demonstrated that parnas is more efficient and flexible than existing approaches. To demonstrate its utility, we applied parnas to 1) quantify SARS-CoV-2 genetic diversity over time, 2) select representative influenza A virus in swine genes derived from over 5 years of genomic surveillance data, and 3) identify gaps in H3N2 human influenza A virus vaccine coverage. We suggest that our method, through the objective selection of representatives in a phylogeny, provides criteria for quantifying genetic diversity that has application in the the rational design of multivalent vaccines and genomic epidemiology. PARNAS is available at https://github.com/flu-crew/parnas. [ABSTRACT FROM AUTHOR]

The ability to provision offspring with milk is a significant adaptive feature of mammals that allows for considerable maternal regulation of offspring beyond gestation, as milk provides complete nutrition for developing neonates. For mothers, lactation is a period of marked increases in energetic and nutritive demands to support milk synthesis; because of this considerable increase in demand imposed on multiple physiological systems, lactation is particularly susceptible to the effects of chronic stress. Here, we present work that explores the impact of chronic stress during lactation on maternal lactation performance (i.e. milk quality and quantity) and the expression of key milk synthesis genes in mammary tissue using a Sprague–Dawley rat model. We induced chronic stress using a well-established, ethologically relevant novel male intruder paradigm for 10 consecutive days during the postpartum period. We hypothesized that the increased energetic burden of mounting a chronic stress response during lactation would decrease lactation performance. Specifically, we predicted that chronic exposure to this social stressor would decrease either milk quality (i.e. composition of proximate components and energy density) or quantity. We also predicted that changes in proximate composition (i.e. lipid, lactose, and protein concentrations) would be associated with changes in gene expression levels of milk synthesis genes. Our results supported our hypothesis that chronic stress impairs lactation performance. Relative to the controls, chronically stressed rats had lower milk yields. We also found that milk quality was decreased; milk from chronically stressed mothers had lower lipid concentration and lower energy density, though protein and lactose concentrations were not different between treatment groups. Although there was a change in proximate composition, chronic stress did not impact mammary gland expression of key milk synthesis genes. Together, this work demonstrates that exposure to a chronic stressor impacts lactation performance, which in turn has the potential to impact offspring development via maternal effects. [ABSTRACT FROM AUTHOR]

Meiotic recombination is both a fundamental biological process required for proper chromosomal segregation during meiosis and an important genomic parameter that shapes major features of the genomic landscape. However, despite the central importance of this phenotype, we lack a clear understanding of the selective pressures that shape its variation in natural populations, including humans. While there is strong evidence of fitness costs of low rates of recombination, the possible fitness costs of high rates of recombination are less defined. To determine whether a single lower fitness bound can explain the variation in recombination rates observed in human populations, we simulated the evolution of recombination rates as a sexually dimorphic quantitative trait. Under each scenario, we statistically compared the resulting trait distribution with the observed distribution of recombination rates from a published study of the Icelandic population. To capture the genetic architecture of recombination rates in humans, we modeled it as a moderately complex trait with modest heritability. For our fitness function, we implemented a hyperbolic tangent curve with several flexible parameters to capture a wide range of existing hypotheses. We found that costs of low rates of recombination alone are likely insufficient to explain the current variation in recombination rates in both males and females, supporting the existence of fitness costs of high rates of recombination in humans. With simulations using both upper and lower fitness boundaries, we describe a parameter space for the costs of high recombination rates that produces results consistent with empirical observations. [ABSTRACT FROM AUTHOR]

Using ≈190 000 spectra from the 17th data release of the Sloan Digital Sky Survey (SDSS), we investigate the ultraviolet emission line properties in z ≈ 2 quasars. Specifically, we quantify how the shape of C  iv  λ1549 and the equivalent width (EW) of He  ii  λ1640 depend on the black hole mass and Eddington ratio inferred from Mg  ii  λ2800. Above L / L Edd ≳ 0.2, there is a strong mass dependence in both C  iv blueshift and He  ii EW. Large C  iv blueshifts are observed only in regions with both high mass and high accretion rate. Including X-ray measurements for a subsample of 5000 objects, we interpret our observations in the context of AGN accretion and outflow mechanisms. The observed trends in He  ii and 2 keV strength are broadly consistent with theoretical qsosed models of AGN spectral energy distributions (SEDs) for low spin black holes, where the ionizing SED depends on the accretion disc temperature and the strength of the soft excess. High spin models are not consistent with observations, suggesting SDSS quasars at z ≈ 2 may in general have low spins. We find a dramatic switch in behaviour at L / L Edd ≲ 0.1: the ultraviolet emission properties show much weaker trends, and no longer agree with qsosed predictions, hinting at changes in the structure of the broad line region. Overall, the observed emission line trends are generally consistent with predictions for radiation line driving where quasar outflows are governed by the SED, which itself results from the accretion flow and hence depends on both the SMBH mass and accretion rate. [ABSTRACT FROM AUTHOR]

Social workers play a critical role in modern public defender offices, whether performing mitigation work for pretrial negotiations and sentencing hearings or helping clients to secure access to basic human needs. Although social workers have held in-house positions in public defender offices since at least the 1970s, their service is largely limited to mitigation practice and traditional social work. This article raises an opportunity for social workers to broaden their capacity within public defense by pursuing investigator positions. A case is made for interested social workers to draw upon their education, training, and experience to showcase the alignment between their talents and the requisite skills and performance required of investigative work. Evidence is offered to support the notion that social workers bring skills and a social justice orientation to investigative work that can provide for fresh insight and innovation in investigation and defense strategy. The value brought to investigation by social workers throughout a legal defense is specified, as are considerations for applying and interviewing for investigator positions as social workers. [ABSTRACT FROM AUTHOR]

Sharing cancer gene variant and relevant clinical data could accelerate progress in cancer genomics. However, data sharing is currently impeded by issues related to financial sustainability, equity, incentives, privacy and security, and data quality. Evidence-based policy options to facilitate data sharing in these domains, and ultimately improve interpretation of cancer-associated genomic variants, are therefore needed. We conducted a modified policy Delphi with expert stakeholders that involved generating, evaluating, and ranking potential policy options to address these issues, with a focus on the US context. We found policy options in the financial sustainability domain were highly ranked, particularly stable funding for trusted entities. However, some Delphi panelists noted that the culture of public research funding has favored short-term grants. Panelists favored policy options focused on action by funders, which had the highest overall total scores that combined effectiveness and feasibility ratings and priority ranking within domains. Panelists also endorsed some policy options connected to actors such as journals, but they were more skeptical of policy options connected to legislative actors and data resources. These findings are critical inputs for policy makers as they consider policies to enable sharing of cancer gene variant data to improve health. [ABSTRACT FROM AUTHOR]

BACKGROUND Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero , to normal cell turnover during adulthood, as well as the elimination of infected or damaged cells throughout life. Quality control through regulation of cell death pathways is particularly important in the germline, which is responsible for the generation of offspring. Women are born with their entire supply of germ cells, housed in functional units known as follicles. Follicles contain an oocyte, as well as specialized somatic granulosa cells essential for oocyte survival. Follicle loss—via regulated cell death—occurs throughout follicle development and life, and can be accelerated following exposure to various environmental and lifestyle factors. It is thought that the elimination of damaged follicles is necessary to ensure that only the best quality oocytes are available for reproduction. OBJECTIVE AND RATIONALE Understanding the precise factors involved in triggering and executing follicle death is crucial to uncovering how follicle endowment is initially determined, as well as how follicle number is maintained throughout puberty, reproductive life, and ovarian ageing in women. Apoptosis is established as essential for ovarian homeostasis at all stages of development and life. However, involvement of other cell death pathways in the ovary is less established. This review aims to summarize the most recent literature on cell death regulators in the ovary, with a particular focus on non-apoptotic pathways and their functions throughout the discrete stages of ovarian development and reproductive life. SEARCH METHODS Comprehensive literature searches were carried out using PubMed and Google Scholar for human, animal, and cellular studies published until August 2022 using the following search terms: oogenesis, follicle formation, follicle atresia, oocyte loss, oocyte apoptosis, regulated cell death in the ovary, non-apoptotic cell death in the ovary, premature ovarian insufficiency, primordial follicles, oocyte quality control, granulosa cell death, autophagy in the ovary, autophagy in oocytes, necroptosis in the ovary, necroptosis in oocytes, pyroptosis in the ovary, pyroptosis in oocytes, parthanatos in the ovary, and parthanatos in oocytes. OUTCOMES Numerous regulated cell death pathways operate in mammalian cells, including apoptosis, autophagic cell death, necroptosis, and pyroptosis. However, our understanding of the distinct cell death mediators in each ovarian cell type and follicle class across the different stages of life remains the source of ongoing investigation. Here, we highlight recent evidence for the contribution of non-apoptotic pathways to ovarian development and function. In particular, we discuss the involvement of autophagy during follicle formation and the role of autophagic cell death, necroptosis, pyroptosis, and parthanatos during follicle atresia, particularly in response to physiological stressors (e.g. oxidative stress). WIDER IMPLICATIONS Improved knowledge of the roles of each regulated cell death pathway in the ovary is vital for understanding ovarian development, as well as maintenance of ovarian function throughout the lifespan. This information is pertinent not only to our understanding of endocrine health, reproductive health, and fertility in women but also to enable identification of novel fertility preservation targets. [ABSTRACT FROM AUTHOR]

We read with great interest Dr Benatar and colleagues' detailed description of pre-diagnosis periods in amyotrophic lateral sclerosis (ALS).[1] We are a group of people living with (or affected by) genetic forms of ALS/FTD (frontotemporal dementia). In response to the forthcoming FDA review of an antisense oligonucleotide targeting therapy for the treatment of SOD1-associated ALS, we conducted a survey of presymptomatic ALS/FTD gene carriers using Google forms via email and social media.[2] The anonymous survey was fielded on 30 September 2022 and closed on 21 October 2022. At a recent FDA patient-led listening session, one of the directors of the Division of Neurology 1 agreed, stating, 'Well, I just want to be clear that from the FDA's perspective, we do consider the presymptomatic stage in genetic mutation carriers as part of the ALS disease process. [Extracted from the article]

Recently, lysergic acid diethylamide (LSD) has become a resurgent drug of abuse. The detection of LSD is problematic because of the low dosage taken by users, light and heat sensitivity of the analyte and the lack of efficient analytical methods. Presented here is the validation of an automated sample preparation method for the analysis of LSD and its primary urinary metabolite, 2-oxo-3-hydroxy-LSD (OHLSD), in urine samples by liquid chromatography–tandem mass spectrometry. Analytes were extracted from urine using an automated Dispersive Pipette XTRaction method on Hamilton STAR and STARlet liquid handling systems. The limit of detection for both analytes was administratively defined at the lowest calibrator used in the experiments, and the limit of quantitation was 0.05 ng/mL for both analytes. All validation criteria were acceptable per Department of Defense Instruction 1010.16 requirements. This method offers an efficient, sensitive analytical solution to routinely evaluate large numbers of urine specimens for LSD in workplace drug deterrence programs. [ABSTRACT FROM AUTHOR]

Prolonged coronavirus disease 2019 may generate new viral variants. We report an immunocompromised patient treated with monoclonal antibodies who experienced rebound of viral RNA and emergence of an antibody-resistant (>1000-fold) variant containing 5 mutations in the spike gene. The mutant virus was isolated from respiratory secretions, suggesting the potential for secondary transmission. [ABSTRACT FROM AUTHOR]

The pBR322 plasmid DNA was irradiated with 35 MeV electrons, 228 MeV protons and 300 kVp X-rays to quantify DNA damage and make comparisons of DNA damage between radiation modalities. Plasmid was irradiated in a medium containing hydroxyl radical scavengers in varying concentrations. This altered the amount of indirect hydroxyl-mediated DNA damage, to create an environment that is more closely associated with a biological cell. We show that increasing hydroxyl scavenger concentration significantly reduced post-irradiation DNA damage to pBR322 plasmid DNA consistently and equally with three radiation modalities. At low scavenging capacities, irradiation with both 35 MeV electrons and 228 MeV protons resulted in increased DNA damage per dose compared with 300 kVp X-rays. We quantify both single-strand break (SSB) and double-strand break (DSB) induction between the modalities as a ratio of yields relative to X-rays, referred to as relative biological effectiveness (RBE). RBESSB values of 1.16 ± 0.15 and 1.18 ± 0.08 were calculated for protons and electrons, respectively, in a low hydroxyl scavenging environment containing 1 mM Tris–HCl for SSB induction. In higher hydroxyl scavenging capacity environments (above 1.1 × 106 s−1), no significant differences in DNA damage induction were found between radiation modalities when using SSB induction as a measure of RBE. Considering DSB induction, significant differences were only found between X-rays and 35 MeV electrons, with an RBEDSB of 1.72 ± 0.91 for 35 MeV electrons, indicating that electrons result in significantly more SSBs and DSBs per unit of dose than 300 kVp X-rays. [ABSTRACT FROM AUTHOR]

Few studies have assessed the association between endogenous steroid hormone levels and a subsequent diagnosis of endometriosis. We prospectively evaluated premenopausal plasma sex hormone levels and the risk of laparoscopically confirmed endometriosis in a nested case-control study within Nurses' Health Study II. Between blood collection (1996–1999) and 2009, we ascertained 446 women with incident endometriosis and matched them to 878 controls through risk-set sampling. We conducted multivariable conditional logistic regression accounting for matching and confounders to estimate relative risks (RRs) and 95% confidence intervals (CIs). Women with greater early follicular-phase total or free estradiol levels had a nonlinear increased risk of endometriosis (early follicular total estradiol: second quartile vs. first, RR = 2.23 (95% CI: 1.44, 3.47); third quartile, RR = 1.83 (95% CI: 1.16, 2.88); fourth quartile, RR = 1.68 (95% CI: 1.05, 2.68); early follicular free estradiol: second quartile vs. first, RR = 1.63 (95% CI: 1.05, 2.54); third quartile, RR = 2.02 (95% CI: 1.31, 3.12); fourth quartile, RR = 1.04 (95% CI: 0.66, 1.65)). Free testosterone assessed in quartile categories was not associated with endometriosis, although a threshold effect was observed, with a positive association among women in the top 2% of free testosterone levels. Levels of mid–luteal-phase total and free estradiol, follicular and luteal estrone, total testosterone, progesterone, and sex hormone binding globulin were not associated with endometriosis risk. These results support the role of sex steroids in endometriosis etiology, although the relationships suggest complex threshold effects. [ABSTRACT FROM AUTHOR]

Background and Aims Mesenchymal stem cells [MSCs] have been used for the treatment of perianal Crohn's fistulising disease by direction injection. No studies to date have included patients with an ileal pouch-anal anastomosis [IPAA] in situ. Methods A phase IB/IIA, randomised, control trial of bone marrow-derived, allogeneic MSCs via direct injection to treat adult patients with a peripouch fistula[s] was conducted; 75 million MSCs were administered with a 22 G needle, with repeat injection at 3 months if complete clinical and radiographic healing was not achieved. Adverse and serious adverse events at post-procedure Day 1, Week 2, Week 6, Month 3, Month 6, and Month 12 were assessed. Clinical healing, radiographic healing per pelvic magnetic resonance imaging [MRI], and patient-reported outcomes were assessed at the same time points. Results A total of 22 patients were enrolled and treated; 16 were treated and six were controls. There were no adverse or serious adverse events related to MSC therapy. At 6 months, 31% of the treatment group and 20% of the control had complete clinical and radiographic healing. When stratifying the treatment group into perianal [ n  = 7] and ano-vaginal [ n  = 8] fistulas, 6-month healing in the treatment groups was 57% and 0%, respectively. The perianal Crohn's disease activity index [PCDAI], Wexner incontinence score, and van Assche score all significantly decreased in treatment patients at 6 months; only the PCDAI decreased in the control group. Conclusion Bone marrow-derived, allogeneic MSCs offer a safe and effective alternative treatment approach for peripouch fistulas in the setting of a Crohn's like phenotype of the pouch [ClinicalTrials.gov Identifier: NCT04519684.] [ABSTRACT FROM AUTHOR]

Background Beginning in late 2021, we observed a significant increase in SARS-CoV-2 reinfections in pediatric patients evaluated at our institution. We aimed to characterize the children with SARS-CoV-2 reinfection, determine the number of SARS-CoV-2 reinfections, and characterize the intervals between two infections in our patient population. Methods From March 2020 to September 2022, we identified children ≤21 years old who had ≥2 SARS-CoV-2 infections using laboratory reports. We then defined the type of SARS-CoV-2 variant in the first and subsequent infections by mutation-specific typing or local epidemiology data. Clinical outcomes and the intervals between SARS-CoV-2 infections were assessed. Results We identified 541 children with ≥2 SARS-CoV-2 infections. The median interval between two infections was 229 days. The hospitalization rate was lower in the second infection. Reinfection counts were higher during the periods that Omicron variants predominated. Reinfection occurred more rapidly when Omicron variants were circulating with some occurring in less than 90 days. Conclusions As SARS-CoV-2 continues to evolve, there is a need for ongoing surveillance to identify the frequency and time interval between reinfections and to re-evaluate the definition of SARS-CoV-2 reinfections. [ABSTRACT FROM AUTHOR]

Background and Aims Rectovaginal fistula occurs in up to 10–20% of women with Crohn's disease, significantly affecting their quality of life. We sought to determine outcomes of single and repeat operative interventions. Methods A retrospective review of all adult patients with a Crohn's-related rectovaginal fistula, who underwent an operation between 1995 and 2021, was performed. Data collected included patient demographics, Crohn's-related medical treatment, surgical intervention, postoperative outcomes, and fistula outcomes. Results A total of 166 patients underwent 360 operations; mean age was 42.8 [+/-13.2] years; 34 [20.7%] patients were current and 58 [35.4%] former smokers. The most commonly performed procedure was: a local approach [ n  = 160, 44.5%] using fibrin glue, fistulotomy/fistulectomy, or seton placement; followed by a transvaginal/transanal approach [ n  = 113, 31.4%] with an advancement flap repair [including Martius advancement flap] and episoproctotomy; a transabdominal approach [ n  = 98, 27.2%] including proctectomy or re-do anastomosis; and finally gracilis muscle interposition [ n  = 8, 2.2%]. The median number of operative interventions per patient was 2 [1.0–3.0] procedures. The overall fistula healing rate per patient was 71.7% [ n  = 119] at a median follow-up of 5.5 [1.2–9.8] years. Factors that impaired healing included former smoking (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.31–0.87, p  = 0.014) and seton insertion [OR 0.42, 95% CI 0.21–0.83, p  = 0.012]. Conclusion Over two-thirds of Crohn's-related rectovaginal fistulas can achieve closure with multiple surgical interventions. Smoking and seton usage negatively affect healing rates and should be avoided. [ABSTRACT FROM AUTHOR]

Background Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disease characterized by painful nodules, drainage and scarring in skin folds. Injectable adalimumab is the only drug approved by the US Food and Drug Administration for the treatment of HS. Although systemic Janus kinase (JAK) inhibitors show promise, serious side-effects have been reported. There are no highly effective topical treatments for HS; furthermore, the contribution of epidermal keratinocytes to the intense inflammation has largely been unexplored. Objectives We investigated the role of keratinocytes and epidermal immune cells in HS inflammation at all Hurley stages of disease severity. We aimed to determine whether ruxolitinib can mitigate inflammation from keratinocytes and to develop a better understanding of how topical therapeutics might benefit patients with HS. Methods We used skin samples from 87 patients with HS (Hurley stages I–III) and 39 healthy controls to compare keratinocyte- and immune cell-driven epidermal inflammation, in addition to the response of lesional HS keratinocytes to treatment with interferon (IFN)-γ and ruxolitinib. We used haematoxylin and eosin staining, immunohistochemistry, immunoblotting and quantitative reverse-transcription polymerase chain reaction assessments in whole skin, isolated epidermis, and cultured keratinocytes from healthy controls and both nonlesional and lesional HS skin to identify and define epidermal and keratinocyte-mediated inflammation in HS and how this may be targeted by therapeutics. Results HS lesional keratinocytes autonomously secreted high levels of chemokines, such as CCL2, CCL3 and CXCL3, which recruited neutrophils, CD8 T cells, and natural killer cells to the epidermis. Keratinocytes were the dominant source of tumour necrosis factor-α and interleukin (IL)-6 in HS lesions with little to no contribution from underlying dermal immune cells. In the presence of IFN-γ, which is dependent on immune cell infiltrate in vivo , keratinocytes expressed increased levels of additional cytokines including IL-1β, IL-12, IL-23 and IL-36γ. The JAK inhibitor ruxolitinib mitigated the expression of inflammatory cytokines and chemokines in HS lesional keratinocytes, thus providing a rationale for future study as a topical treatment for HS. Conclusions This study demonstrates that keratinocytes actively recruit immune cells to HS epidermis and interactions between these cells drive a broad inflammatory profile in HS epidermis. Targeting epidermal inflammation in HS with novel topical formulations may be highly efficacious with reduced systemic side-effects. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare results from five commercial hair testing laboratories conducting workplace drug testing with regard to bias, precision, selectivity and decontamination efficiency. Nine blind hair specimens, including cocaine-positive drug user specimens (some contaminated with methamphetamine) and negative specimens contaminated with cocaine, were submitted in up to five replicates to five different laboratories. All laboratories correctly identified cocaine in all specimens from drug users. For an undamaged hair specimen from a cocaine user, within-laboratory Coefficients of Variation (CVs) of 5–22% (median 8%) were reported, showing that it is possible to produce a homogenous proficiency testing sample from drug user hair. Larger CVs were reported for specimens composed of blended hair (up to 29%) and curly/damaged hair (19–67%). Quantitative results appeared to be method-dependent, and the reported cocaine concentrations varied up to 5-fold between the laboratories, making interlaboratory comparisons difficult. All laboratories reported at least one positive result in specimens contaminated with cocaine powder, followed by sweat and shampoo treatments. Benzoylecgonine, norcocaine, cocaethylene and hydroxylated cocaine metabolites were all detected in cocaine powder-contaminated specimens. This indicates that current industry standards for analyzing and reporting positive cocaine results are not completely effective at identifying external contamination. Metabolite ratios between meta - or para -hydroxy-cocaine and cocaine were 6- and 10-fold lower in contaminated specimens compared to those observed in cocaine user specimens, supporting their potential use in distinguishing samples positive due to contamination and drug use. [ABSTRACT FROM AUTHOR]

The evolution of eusociality requires that individuals forgo some or all their own reproduction to assist the reproduction of others in their group, such as a primary egg-laying queen. A major open question is how genes and genetic pathways sculpt the evolution of eusociality, especially in rudimentary forms of sociality—those with smaller cooperative nests when compared with species such as honeybees that possess large societies. We lack comprehensive comparative studies examining shared patterns and processes across multiple social lineages. Here we examine the mechanisms of molecular convergence across two lineages of bees and wasps exhibiting such rudimentary societies. These societies consist of few individuals and their life histories range from facultative to obligately social. Using six species across four independent origins of sociality, we conduct a comparative meta-analysis of publicly available transcriptomes. Standard methods detected little similarity in patterns of differential gene expression in brain transcriptomes among reproductive and non-reproductive individuals across species. By contrast, both supervised machine learning and consensus co-expression network approaches uncovered sets of genes with conserved expression patterns among reproductive and non-reproductive phenotypes across species. These sets overlap substantially, and may comprise a shared genetic "toolkit" for sociality across the distantly related taxa of bees and wasps and independently evolved lineages of sociality. We also found many lineage-specific genes and co-expression modules associated with social phenotypes and possible signatures of shared life-history traits. These results reveal how taxon-specific molecular mechanisms complement a core toolkit of molecular processes in sculpting traits related to the evolution of eusociality. [ABSTRACT FROM AUTHOR]