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Porcine delta-coronavirus (PDCoV) spillovers were recently detected in febrile children, underscoring the recurrent zoonoses of divergent CoVs. To date, no vaccines or specific therapeutics are approved for use in humans against PDCoV. To prepare for possible future PDCoV epidemics, we isolated PDCoV spike (S)-directed monoclonal antibodies (mAbs) from humanized mice and found that two, designated PD33 and PD41, broadly neutralized a panel of PDCoV variants. Cryoelectron microscopy (cryo-EM) structures of PD33 and PD41 in complex with the S receptor-binding domain (RBD) and ectodomain trimer revealed the epitopes recognized by these mAbs, rationalizing their broad inhibitory activity. We show that both mAbs competitively interfere with host aminopeptidase N binding to neutralize PDCoV and used deep-mutational scanning epitope mapping to associate RBD antigenic sites with mAb-mediated neutralization potency. Our results indicate a PD33-PD41 mAb cocktail may heighten the barrier to escape. PD33 and PD41 are candidates for clinical advancement against future PDCoV outbreaks., Competing Interests: Declaration of interests D.V. is named as inventor on patents for CoV nanoparticle vaccines filed by the University of Washington. D.C., L.P., A.D., K.C., C.S., A.B., and F.B. are employees of Vir Biotechnology and may hold shares in Vir Biotechnology., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Current understanding of soil carbon dynamics suggests that plant litter quality and soil mineralogy control the formation of mineral-associated soil organic carbon (SOC). Due to more efficient microbial anabolism, high-quality litter may produce more microbial residues for stabilisation on mineral surfaces. To test these fundamental concepts, we manipulate soil mineralogy using pristine minerals, characterise microbial communities and use stable isotopes to measure decomposition of low- and high-quality litter and mineral stabilisation of litter-C. We find that high-quality litter leads to less (not more) efficient formation of mineral-associated SOC due to soil microbial community shifts which lower carbon use efficiency. Low-quality litter enhances loss of pre-existing SOC resulting in no effect of litter quality on total mineral-associated SOC. However, mineral-associated SOC formation is primarily controlled by soil mineralogy. These findings refute the hypothesis that high-quality plant litters form mineral-associated SOC most efficiently and advance our understanding of how mineralogy and litter-microbial interactions regulate SOC formation., Competing Interests: Competing interests: The authors declare no competing interests, (© 2024. The Author(s).)

The recurring spillover of pathogenic coronaviruses and demonstrated capacity of sarbecoviruses, such SARS-CoV-2, to rapidly evolve in humans underscores the need to better understand immune responses to this virus family. For this purpose, we characterized the functional breadth and potency of antibodies targeting the receptor binding domain (RBD) of the spike glycoprotein that exhibited cross-reactivity against SARS-CoV-2 variants, SARS-CoV-1 and sarbecoviruses from diverse clades and animal origins with spillover potential. One neutralizing antibody, C68.61, showed remarkable neutralization breadth against both SARS-CoV-2 variants and viruses from different sarbecovirus clades. C68.61, which targets a conserved RBD class 5 epitope, did not select for escape variants of SARS-CoV-2 or SARS-CoV-1 in culture nor have predicted escape variants among circulating SARS-CoV-2 strains, suggesting this epitope is functionally constrained. We identified 11 additional SARS-CoV-2/SARS-CoV-1 cross-reactive antibodies that target the more sequence conserved class 4 and class 5 epitopes within RBD that show activity against a subset of diverse sarbecoviruses with one antibody binding every single sarbecovirus RBD tested. A subset of these antibodies exhibited Fc-mediated effector functions as potent as antibodies that impact infection outcome in animal models. Thus, our study identified antibodies targeting conserved regions across SARS-CoV-2 variants and sarbecoviruses that may serve as therapeutics for pandemic preparedness as well as blueprints for the design of immunogens capable of eliciting cross-neutralizing responses., Competing Interests: J.O. is a consultant for Aerium Therapeutics, Inc. J.O. and J.G are listed on a patent application (22-173-US-PSP2) and license agreement with Aerium Therapeutics, Inc. for C68.61. H.Y.C reported consulting with Ellume, Merck, Abbvie, Pfizer, Medscape, Vindico, and the Bill and Melinda Gates Foundation. She has received research funding from Gates Ventures, and support and reagents from Ellume and Cepheid outside of the submitted work. T.N.S. consults for Apriori Bio and Vir Biotechnology on deep mutational scanning. The lab of T.N.S. has received sponsored research agreements unrelated to the present work from Vir Biotechnology, Aerium Therapeutics, Inc. and Invivyd, Inc., (Copyright: © 2024 Ruiz 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.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing coronavirus mAbs that are sufficiently potent for clinical development and retain activity despite viral evolution remain elusive. We identified a human mAb, designated VIR-7229, which targets the viral receptor-binding motif (RBM) with unprecedented cross-reactivity to all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently neutralizing SARS-CoV-2 variants since 2019, including the recent EG.5, BA.2.86, and JN.1. VIR-7229 tolerates extraordinary epitope variability, partly attributed to its high binding affinity, receptor molecular mimicry, and interactions with RBM backbone atoms. Consequently, VIR-7229 features a high barrier for selection of escape mutants, which are rare and associated with reduced viral fitness, underscoring its potential to be resilient to future viral evolution. VIR-7229 is a strong candidate to become a next-generation medicine., Competing Interests: Declaration of interests L.E.R., A.D.M., D.P., D.B., T.R., J.M.E., K.H., H.V.D., M.G., G.C., C.S., F.Z., E.D., A.R., J.N., Q.T., Y.D., B.T., R.A., S.S., B.G., M.A.S., G. Schnell, J.L.M., F.A.L., N.C., E.C., L.A.P., F.B., J.d.I., M.S.P., A.L., A.T., G. Snell, and D.C. are current or previous employees of Vir Biotechnology and may hold shares in Vir Biotechnology. L.E.R., A.D.M., D.P., E.C., F.B., M.S.P., G. Snell, and D.C. are currently listed as inventors on multiple patent applications that disclose the subject matter described in this paper. J.W.C. is an employee and shareholder of ProtaBody. J.W.C. and ProtaBody have received funding from Vir Biotechnology related to the work described in this paper. I.Z., Z.L., S.P.J.W., G.D.d.M., L.K., H.B., and T.N.S. have received funding through sponsored research awards to their respective institutions from Vir Biotechnology related to the work described in this paper. I.Z. is a current employee of Bristol Myers Squibb. L.A.P. is a former employee and shareholder of Regeneron Pharmaceuticals and is a member of the Scientific Advisory Board AI-driven structure-enabled antiviral platform (ASAP). Regeneron provided no funding for this work. L.A.P. is a current employee of Third Rock Ventures. D.V. is named as inventor on patents for coronavirus vaccines filed by the University of Washington. The lab of T.N.S. has received sponsored research agreements unrelated to the present work from Aerium Therapeutics, Inc. and Invivyd, Inc., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Patients maintained on extracorporeal membrane oxygenation (ECMO) often require systemic anticoagulation to prevent circuit clotting and systemic thromboembolic complications. The optimal intensity of anticoagulation to balance the risk of bleeding and prevention of thrombotic complications in this patient population is not well described. Objective: To compare bleeding events in patients on ECMO anticoagulated with standard vs low intensity heparin protocols. Methods: This single-center, retrospective cohort study included adult patients on VA- or VV-ECMO and anticoagulated with low or standard intensity heparin protocols. The primary outcome was the incidence of major bleeding; secondary outcomes included the incidence of minor bleeding, thrombotic complications, heparin-induced thrombocytopenia, in-hospital mortality, time in therapeutic range, anti-Xa correlation with aPTT, intensive care unit and hospital lengths of stay, oxygenator exchanges, and rate of protocol switching. Results: A total of 27 patients (14 low intensity, 13 standard intensity) were included. There were six major bleeding events in the low intensity group and four in the standard intensity group ( P = 0.69); there were four minor bleeding events in the low intensity group and five in the standard intensity group ( P = 0.69). Seven patients in the standard intensity group switched protocols; zero patients in the low intensity group switched protocols ( P = 0.002). There were no differences in any other outcomes. Conclusions: There was no difference in the incidence of any bleeding or thrombotic events when using a low vs standard intensity heparin protocol in patients on ECMO. A low intensity heparin strategy for patients on ECMO may be feasible and safe., 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.

Deep mutational scanning experiments aid in the surveillance and forecasting of viral evolution by providing prospective measurements of mutational effects on viral traits, but epistatic shifts in the impacts of mutations can hinder viral forecasting when measurements were made in outdated strain backgrounds. Here, we report measurements of the impact of all single amino acid mutations on ACE2-binding affinity and protein folding and expression in the SARS-CoV-2 Omicron BA.2.86 spike receptor-binding domain. As with other SARS-CoV-2 variants, we find a plastic and evolvable basis for receptor binding, with many mutations at the ACE2 interface maintaining or even improving ACE2-binding affinity. Despite its large genetic divergence, mutational effects in BA.2.86 have not diverged greatly from those measured in its Omicron BA.2 ancestor. However, we do identify strong positive epistasis among subsequent mutations that have accrued in BA.2.86 descendants. Specifically, the Q493E mutation that decreased ACE2-binding affinity in all previous SARS-CoV-2 backgrounds is reversed in sign to enhance human ACE2-binding affinity when coupled with L455S and F456L in the currently emerging KP.3 variant. Our results point to a modest degree of epistatic drift in mutational effects during recent SARS-CoV-2 evolution but highlight how these small epistatic shifts can have important consequences for the emergence of new SARS-CoV-2 variants., Competing Interests: T.N.S. consults for Apriori Bio, Metaphore Biotechnologies, and Vir Biotechnology on deep mutational scanning. The lab of T.N.S. has received sponsored research agreements unrelated to the present work from Vir Biotechnology, Aerium Therapeutics, Inc., and Invivyd, Inc. T.N.S. may receive a share of intellectual property revenue as inventor on a Fred Hutchinson Cancer Center-optioned patent related to stabilization of SARS-CoV-2 RBDs., (© The Author(s) 2024. Published by Oxford University Press.)

Background: There have only been two efficacy trials reporting a head-to-head comparison of medications and psychotherapy for PTSD, and neither was conducted in primary care. Therefore, this protocol paper describes a pragmatic trial that compares outcomes of primary care patients randomized to initially receive a brief trauma-focused psychotherapy or a choice of three antidepressants. In addition, because there are few trials examining the effectiveness of subsequent treatments for patients not responding to the initial treatment, this pragmatic trial also compares the outcomes of those switching or augmenting treatments., Method: Patients screening positive for PTSD (n = 700) were recruited from the primary care clinics of 7 Federally Qualified Health Centers (FQHC) and 8 Department of Veterans Affairs (VA) Medical Centers and randomized in the ratio 1:1:2 to one of three treatment sequences: 1) selective serotonin reuptake inhibitor (SSRI) followed by augmentation with Written Exposure Therapy (WET), 2) SSRI followed by a switch to serotonin-norepinephrine reuptake inhibitor (SNRI), or 3) WET followed by a switch to SSRI. Participants complete surveys at baseline, 4 months, and 8 months. The primary outcome is PTSD symptom severity as measured by the PTSD Checklist (PCL-5)., Results: Average PCL-5 scores (M = 52.8, SD = 11.1) indicated considerable severity. The most common bothersome traumatic event for VA enrollees was combat (47.8%), and for FQHC enrollees was other (28.2%), followed by sexual assault (23.4%), and child abuse (19.8%). Only 22.4% were taking an antidepressant at baseline., Conclusion: Results will help healthcare systems and clinicians make decisions about which treatments to offer to patients., Competing Interests: Declaration of competing interest The authors do not have any personal, professional, or financial conflicts of interest to disclose for this work., (Published by Elsevier Inc.)

Background: Exposure to arsenic (As) in well water is a well-documented public health issue for Maine and New Hampshire, as well as for other states in the United States and abroad. Arsenic contamination of well water in these locations is primarily attributed to metasedimentary bedrock that leaches As into groundwater. However, As can also enter groundwater reserves from soils contaminated by the historical use of arsenical pesticides. Approximately half of the households in Maine and New Hampshire rely on private wells, many of which have elevated As. Arsenic exposure has been associated with an increased risk of cancer, cardiovascular disease, reduced infection resistance, and lower intelligence quotient in children. Despite these known health impacts, well water testing and treatment are not universal., Objectives: We have approached the problem of low well water testing rates in Maine and New Hampshire communities by developing the All About Arsenic (AAA) project, which engages secondary school teachers and students as citizen scientists in collecting well water samples for analysis of As and other toxic metals and supports their outreach efforts to their communities., Methods: We assessed this project's public health impact by analyzing student data relative to existing well water quality datasets in both states. In addition, we surveyed private well owners who contributed well water samples to the project to determine the actions taken to mitigate As in well water., Results: Students collected 3,070 drinking water samples for metals testing, and 752 exceeded New Hampshire's As standard of 5  ppb . The AAA data has more than doubled the amount of information available to public health agencies about well water quality in multiple municipalities across both states. Students also collected information about well types and treatment systems. Their data reveal that some homeowners did not know what type of wells they had or whether they had filtration systems. Those with filtration systems were often unaware of the type of system, what the system was filtering for, or whether the system was designed to remove As. Through interviews with pilot survey participants, we learned that some had begun mitigating their exposure to As and other toxic metals in response to test results from the AAA project., Discussion: A school-based approach to collecting and analyzing private well water samples can successfully reach communities with low testing rates for toxic elements, such as As and other metals. Importantly, information generated through the program can impact household decision-making, and students can influence local and state policymaking by sharing information in their communities. https://doi.org/10.1289/EHP13421.

Deep mutational scanning experiments aid in the surveillance and forecasting of viral evolution by providing prospective measurements of mutational effects on viral traits, but epistatic shifts in the impacts of mutations can hinder viral forecasting when measurements were made in outdated strain backgrounds. Here, we report measurements of the impact of all single amino acid mutations on ACE2-binding affinity and protein folding and expression in the SARS-CoV-2 Omicron BA.2.86 spike receptor-binding domain (RBD). As with other SARS-CoV-2 variants, we find a plastic and evolvable basis for receptor binding, with many mutations at the ACE2 interface maintaining or even improving ACE2-binding affinity. Despite its large genetic divergence, mutational effects in BA.2.86 have not diverged greatly from those measured in its Omicron BA.2 ancestor. However, we do identify strong positive epistasis among subsequent mutations that have accrued in BA.2.86 descendants. Specifically, the Q493E mutation that decreased ACE2-binding affinity in all previous SARS-CoV-2 backgrounds is reversed in sign to enhance human ACE2-binding affinity when coupled with L455S and F456L in the currently emerging KP.3 variant. Our results point to a modest degree of epistatic drift in mutational effects during recent SARS-CoV-2 evolution but highlight how these small epistatic shifts can have important consequences for the emergence of new SARS-CoV-2 variants., Competing Interests: Competing Interests. T.N.S. consults for Apriori Bio, Metaphore Biotechnologies, and Vir Biotechnology on deep mutational scanning. The lab of T.N.S. has received sponsored research agreements unrelated to the present work from Vir Biotechnology, Aerium Therapeutics, Inc., and Invivyd, Inc. T.N.S. may receive a share of intellectual property revenue as inventor on a Fred Hutchinson Cancer Center-optioned patent related to stabilization of SARS-CoV-2 RBDs.

Coronaviruses have been responsible for numerous viral outbreaks in the past two decades due to the high transmission rate of this family of viruses. The deadliest outbreak is the recent Covid-19 pandemic, which resulted in over 7 million deaths worldwide. SARS-CoV-2 papain-like protease (PL Pro ) plays a key role in both viral replication and host immune suppression and is highly conserved across the coronavirus family, making it an ideal drug target. Herein we describe a fragment-based screen against PL Pro using protein-observed NMR experiments, identifying 77 hit fragments. Analyses of NMR perturbation patterns and X-ray cocrystallized structures reveal fragments bind to two distinct regions of the protein. Importantly none of the fragments identified belong to the same chemical class as the few reported inhibitors, allowing for the discovery of a novel class of PL Pro inhibitors., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The COVID-19 pandemic resulted in increased feelings of emotional distress and disruptions in care across diverse patients subgroups, including those with chronic medical conditions such as inflammatory bowel diseases (IBD). We sought to understand the impact of the pandemic on the physical and emotional well-being of individuals with IBD and concurrent depression and/or anxiety symptoms. We conducted qualitative interviews after the beginning of the pandemic with 46 adults with IBD. Participants reported increased levels of emotional distress, feelings of social isolation, and uncertainty over whether IBD medications put them at increased risk. Young adults discussed feeling as if their lives had been disrupted. In addition, several individuals demonstrated resiliency and emphasized positives about the pandemic, including increased connectivity with family and friends, the convenience of being able to work from home despite their IBD symptoms, and lessened feelings of "missing out." Our findings highlight several opportunities to improve the health and well-being of individuals with IBD and beyond including increased support for combatting social isolation, enhanced counseling about medication risks and benefits, and the incorporation of resiliency skills building., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Critical care pharmacists are considered essential members of the healthcare team; however, justification and recruitment of new positions, especially in the evening or weekend shifts, remains a significant challenge. The purpose of this study was to investigate the number of interventions, type of interventions, and associated cost savings with the addition of 1 board certified critical care clinical pharmacist to evening shift. Methods: This was a prospective collection and characterization of 1 evening shift critical care pharmacist's clinical interventions over a 12-week period. Interventions were collected and categorized daily from 13:00 to 22:00 Monday through Friday. After collection was complete, cost savings estimates were calculated using pharmacy wholesaler acquisition cost. Results: Interventions were collected on 52 of 60 weekdays. A total of 510 interventions were collected with an average of 9.8 interventions accepted per day. The most common interventions included transitions of care, medication dose adjustment, and antibiotic de-escalation and the highest proportion of interventions occurred in the medical intensive care unit. An estimated associated cost avoidance of $66 537.80 was calculated for an average of $1279.57 saved per day. Additionally, 22 (4.1%) of interventions were considered high yield interventions upon independent review by 2 pharmacists. Conclusion: The addition of 1 board-certified critical care pharmacist to evening shift resulted in multiple interventions across several categories and a significant cost avoidance when calculated using conservative measures., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Sikora has received research funding through the Agency for Healthcare Quality and Research (AHRQ) under Award Number R21HS028485 and R01HS029009., (© The Author(s) 2023.)

Participants were 85 individuals who made suicide attempts within two years of their Improving Access to Psychological Therapies (IAPT) assessment, identified using record linkage. Two comparison groups, non-suicidal controls ( n  = 1416) and (ideators, n  = 743) were compared on variables extracted from the standardized IAPT risk assessment interview. Disclosure of a historical suicide attempt or non-suicidal self-injury (NSSI) distinguished those making an attempt from those with suicidal ideation only, but suicidal intent did not. A third of the participants concealed a historical suicide attempt. The IAPT Phobia Scale classified 49.30% of attempters with 100% specificity. The IAPT Phobia Scale may have clinical value in assessing risk but requires validation. Past suicide attempt and NSSI have better clinical risk assessment utility than current suicidal ideation intensity. Risk assessment relying on disclosure is likely to be flawed and risks support being withheld from those assumed to be at lower risk.

US female veterans have higher rates of mental health (MH) disorders compared to US civilian females and, consequently, are at risk for poor MH outcomes during pregnancy. This study evaluated the MH burden and identified the prevalence of antidepressant prescription and discontinuation among pregnant veterans (PGVets). The electronic health records (EHR) of PGVets using the US Veterans Administration's (VA) maternity care benefits over a two-year period were retrospectively reviewed. Inclusion criteria for this study were a current MH diagnosis of depression, anxiety, or posttraumatic stress disorder (PTSD) at the onset of pregnancy (n=351). Outcomes examined included antidepressant use prior to pregnancy, the use and discontinuation of antidepressants during pregnancy, and risk factors for discontinuation. PGVets had a high MH burden, as indicated by multiple comorbid diagnoses of unipolar depression, anxiety, and PTSD in 67% of the sample. At the onset of pregnancy, 163 (46%) were treated with an antidepressant. Only 56 (34%) continued using antidepressants through the pregnancy. Self-discontinuation (34%) and VA provider discontinuation (31%) of antidepressants were found. Among PGVets with documented past suicidal behaviors, 90% discontinued their active antidepressants. PGVets with indicators for more severe MH diagnoses were most likely to discontinue. The MH burden of PGVets and high rates of antidepressant discontinuation have implications for engaging this population in a higher level of perinatal monitoring and intervention. The findings suggest that VA providers and veterans would benefit from risks and benefits education regarding antidepressant use during pregnancy as well as the provision of alternative therapies., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Amidst the dual challenges of an eight-month university closure from nationwide public university strikes in Nigeria and the lingering impacts of the Covid-19 pandemic, we needed to innovate the delivery of BME graduate curriculum to ensure graduate students continued to progress in their studies. To ensure BME graduate students were engaging in team-based, clinician-identified engineering design challenges, we developed a digital design notebook (DDN) using Google Sites as an open-access, collaborative tool for scaffolding and documenting the engineering design process. Student design teams remotely uploaded digital content documenting their project work onto scaffolded DDNs created by program instructors. DDNs were purposefully designed to shepherd students through the design process such that each phase of the design process corresponded to an editable "page" of the DDN. Video lectures, learning resources, assignments, and other program information were embedded into the DDN for students to access throughout their design challenge. Project mentors and program instructors remotely monitored and assessed students' work using the DDN. At the end of the design challenge, students effectively created an e-portfolio which showcased the work they conducted to build a biomedical prototype. Designing and implementing the DDN builds on previous research which demonstrates that "structured" design notebooks can be used as effective tools in engineering design and design thinking education. Our work also leverages educational frameworks for infusing engineering design into existing graduate biomedical engineering curriculum in Nigeria., Competing Interests: Conflict of interestThe author declares that they have no competing interests., (© The Author(s) 2024.)

Substitutions that fix between SARS-CoV-2 variants can transform the mutational landscape of future evolution via epistasis. For example, large epistatic shifts in mutational effects caused by N501Y underlied the original emergence of Omicron, but whether such epistatic saltations continue to define ongoing SARS-CoV-2 evolution remains unclear. We conducted deep mutational scans to measure the impacts of all single amino acid mutations and single-codon deletions in the spike receptor-binding domain (RBD) on ACE2-binding affinity and protein expression in the recent Omicron BQ.1.1 and XBB.1.5 variants, and we compared mutational patterns to earlier viral strains that we have previously profiled. As with previous deep mutational scans, we find many mutations that are tolerated or even enhance binding to ACE2 receptor. The tolerance of sites to single-codon deletion largely conforms with tolerance to amino acid mutation. Though deletions in the RBD have not yet been seen in dominant lineages, we observe tolerated deletions including at positions that exhibit indel variation across broader sarbecovirus evolution and in emerging SARS-CoV-2 variants of interest, most notably the well-tolerated Δ483 deletion in BA.2.86. The substitutions that distinguish recent viral variants have not induced as dramatic of epistatic perturbations as N501Y, but we identify ongoing epistatic drift in SARS-CoV-2 variants, including interaction between R493Q reversions and mutations at positions 453, 455, and 456, including F456L that defines the XBB.1.5-derived EG.5 lineage. Our results highlight ongoing drift in the effects of mutations due to epistasis, which may continue to direct SARS-CoV-2 evolution into new regions of sequence space., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: T.N.S. consults for Apriori Bio, Metaphore Biotechnologies, and Vir Biotechnology on deep mutational scanning. The lab of T.N.S. has received sponsored research agreements unrelated to the present work from Vir Biotechnology and Aerium Therapeutics, Inc. T.N.S. may receive a share of intellectual property revenue as inventor on a Fred Hutchinson Cancer Center-optioned patent related to stabilization of SARS-CoV-2 RBDs., (Copyright: © 2023 Taylor, Starr. 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.)

Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. Here, we show that the African Rhinolophus bat clade 3 sarbecovirus PRD-0038 S has a broad angiotensin-converting enzyme 2 (ACE2) usage and that receptor-binding domain (RBD) mutations further expand receptor promiscuity and enable human ACE2 utilization. We determine a cryo-EM structure of the PRD-0038 RBD bound to Rhinolophus alcyone ACE2, explaining receptor tropism and highlighting differences with SARS-CoV-1 and SARS-CoV-2. Characterization of PRD-0038 S using cryo-EM and monoclonal antibody reactivity reveals its distinct antigenicity relative to SARS-CoV-2 and identifies PRD-0038 cross-neutralizing antibodies for pandemic preparedness. PRD-0038 S vaccination elicits greater titers of antibodies cross-reacting with vaccine-mismatched clade 2 and clade 1a sarbecoviruses compared with SARS-CoV-2 S due to broader antigenic targeting, motivating the inclusion of clade 3 antigens in next-generation vaccines for enhanced resilience to viral evolution., Competing Interests: Declaration of interests N.P.K. and D.V. are named as inventors on patents for coronavirus nanoparticle vaccines filed by the University of Washington. N.P.K. is a co-founder, shareholder, paid consultant, and chair of the scientific advisory board of Icosavax, Inc. and has received an unrelated sponsored research agreement from Pfizer. D.C. is an employee of Vir Biotechnology and may hold shares in Vir Biotechnology. T.N.S. consults for Apriori Bio on DMS. The lab of T.N.S. has received sponsored research agreements unrelated to the present work from Vir Biotechnology and Aerium Therapeutics, Inc. T.N.S. may receive a share of intellectual property revenue as inventor on a Fred Hutchinson Cancer Center-optioned patent related to stabilization of SARS-CoV-2 RBDs. The remaining 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to determine the relationship between medication regimen complexity-intensive care unit (MRC-ICU) score at 24 hours and medication errors identified throughout the ICU. Methods: A single-center, observational study was conducted from August to October 2021. The primary outcome was the association between MRC-ICU at 24 hours and total medication errors identified. During the prospective component, ICU pharmacists recorded medication errors identified over an 8-week period. During the retrospective component, the electronic medical record was reviewed to collect patient demographics, outcomes, and MRC-ICU score at 24 hours. The primary outcome of the relationship of MRC-ICU at 24 hours to medication errors was assessed using Pearson correlation. Results: A total of 150 patients were included. There were 2 pharmacists who recorded 634 errors during the 8-week study period. No significant relationship between MRC-ICU and medication errors was observed ( r 2  = .13, P  = .11). Exploratory analyses of MRC-ICU relationship to major interventions and harm scores showed that MRC-ICU scores >10 had more major interventions (27 vs 14, P  = .27) and higher harm scores (15 vs 7, P  = .33), although these values were not statistically significant. Conclusion: Medication errors appear to occur independently of medication regimen complexity. Critical care pharmacists were responsible for mitigating a large number of medication errors., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Many adolescent health surveys ask if respondents are male or female. Non-response may be due to fear of de-anonymisation or being a gender-nonconforming youth. The present study investigates the frequency of non-response and its potential reasons. To this end, data from 54,833 adolescents aged 11-18 from six countries, participating in the 2018 Health Behaviour in School-aged Children (HBSC) study, were analysed. Respondents were divided into three groups: (1) "Responders" who answered both questions on age and gender, (2) "Age non-responders" who did not answer the question on age, and (3) "Gender non-responders" who answered the question on age but not the one on gender. These groups were compared regarding their non-response to other questions and regarding their health. Overall, 98.0% were responders, 1.6% were age non-responders and 0.4% were gender non-responders. On average, age non-responders skipped more questions (4.2 out or 64) than gender non-responders (3.2) and responders (2.1). Gender non-responders reported more psychosomatic complaints, more frequent substance use and lower family support than responders. This study shows that age and gender non-responders differ in their response styles, suggesting different reasons for skipping the gender question. The health disparities found between the groups suggest that further research should use a more nuanced approach, informed by LGBT+ youth's insights, to measure sex assigned at birth and gender identity.

Purpose: Studying physical activity in toddlers using accelerometers is challenging due to noncompliance with wear time (WT) and activity log (AL) instructions. The aims of this study are to examine relationships between WT and AL completion and (1) demographic and socioeconomic variables, (2) parenting style, and (3) whether sedentary time differs by AL completion., Methods: Secondary analysis was performed using baseline data from a community wellness program randomized controlled trial for parents with toddlers (12-35 mo). Parents had toddlers wear ActiGraph wGT3x accelerometers and completed ALs. Valid days included ≥600-minute WT. Analysis of variance and chi-square analyses were used., Results: The sample (n = 50) comprised racial and ethnically diverse toddlers (mean age = 27 mo, 58% male) and parents (mean age = 31.7 y, 84% female). Twenty-eight families (56%) returned valid accelerometer data with ALs. Participants in relationships were more likely to complete ALs (P < .05). Toddler sedentary time did not differ between those with ALs and those without., Conclusions: We found varied compliance with WT instructions and AL completion. Returned AL quality was poor, presenting challenges in correctly characterizing low-activity counts to improve internal validity of WT and physical activity measures. Support from marital partners may be important for adherence to study protocols.

Background: Extracorporeal photopheresis (ECP) is frequently utilized in the treatment of steroid-refractory acute and chronic graft-versus-host disease (GVHD). Although the mechanism of action is not fully understood, it has been postulated that its therapeutic effect is immunologic tolerance linked to the associated apoptosis of the treated cells. Despite significant advances in allogeneic hematopoietic stem cell transplantation (HSCT), prophylaxis and treatment of GVHD remain a challenge and major limitation associated with this therapy. Use of ECP is a valuable strategy; however, it is time, cost, resource intensive, and not readily accessible., Objective: In an effort to expand access to this therapy, we are investigating the use of cryopreserved ECP-treated cells. This will provide the ability to administer a significant proportion of the treatment at a facility closer to the patient's residence, thereby decreasing the number of visits to the primary treatment center with the goal of improving and expanding access to this therapy. Here we report the effects of cryopreservation on ECP-treated leukocytes., Study Design: Mononuclear cells were pheresed from human patients, ECP-treated, and collected for viability and apoptotic analysis. Cells were then cryopreserved at -80°C or -150°C for 1 week, 1 month, and 3 months. Following thaw, repeat viability and apoptosis studies were performed on the leukocytes., Results: WBC viability for freshly ECP-treated leukocytes was 84.5% ± 3.5 at 1 week, 87.3% ± 5.2 at 1 month, and 79.1% ± 1.1 at 3 months post thaw. Similar results were seen for cells frozen in cryovials. Leukocytes frozen the day after ECP treatment had 1 week and 1 month WBC viabilities of 84.0 ± 4.1 and 83.1 ± 2.1, respectively. Apoptotic potential was well preserved at 3 months, with cryopreserved ECP-treated lymphocytes being 19.2%, 44.5%, 75.5%, and 94.0% apoptotic after thaw on days 0, 1, 2, and 3 in culture, respectively., Conclusions: ECP-treated leukocytes cryopreserved at -80°C or -150°C for 3 months remain viable and as capable of apoptosis as freshly treated cells. Cryopreservation of an ECP-product warrants further in vivo investigation as a strategy to facilitate access to this needed therapy., Competing Interests: Declarations of competing Interest None, (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose: Transgender and nonbinary (TNB) youth face elevated levels of discrimination, stigma, mental health disorders, and suicidality when compared with their cisgender counterparts. Family and school support may mitigate some of the effects of the stressors facing TNB youth. This study aimed to better understand the impact of each of these sources of support on TNB youths' mental health and wellbeing. Methods: We used data collected between 2018 and 2019 as part of the Canadian Trans Youth Health Survey, a bilingual online survey to measure social support, physical health, and mental health in a sample of 220 TNB youth aged 14-25 living in Québec, Canada. We examined the relationships among different sources of support, and mental health and wellbeing outcomes using logistic regression. Analyses were conducted on the full sample and according to linguistic groups (French and English). Results: Participants reported high levels of mental health symptoms, self-harm, and suicidality, and mental health symptoms were higher in the English-speaking group ( p  = 0.005). In models controlling for age, family connectedness was associated with good/excellent self-reported mental health (odds ratio [OR] = 2.62, p  = 0.001) and lower odds of having considered suicide (OR = 0.49, p  = 0.003) or attempted suicide (OR = 0.43, p  = 0.002), whereas school connectedness was associated with higher odds of good/very good/excellent general (OR = 2.42, p  = 0.013) and good/excellent mental (OR = 2.45, p  = 0.045) health. Conclusion: Family and school support present consistent associations with TNB youths' health and may constitute key areas for intervention for those supporting them.

Diagnosis and treatment of postconcussional syndrome (PCS) is challenging because symptoms are vague, difficult to confirm, and attributable to other conditions. There are no uniformly accepted diagnostic PCS criteria. Clinical care largely focuses on symptom reduction and management. Moreover, the coronavirus disease 2019 (COVID-19) pandemic has increased the challenge because post-acute COVID-19 syndrome symptoms overlap with PCS. Future research should center on base rates of PCS-type symptoms in nonneurological samples and the identification and improved understanding of moderating variables contributing to the frequency, intensity, and duration of PCS symptoms., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Cardiothoracic surgical critical care medicine (CT-CCM) is a medical discipline centered on the perioperative care of diverse groups of patients. With an aging demographic and an increase in burden of chronic diseases the utilization of cardiothoracic surgical critical care units is likely to escalate in the coming decades. Given these projections, it is important to assess the state of cardiothoracic surgical intensive care, to develop goals and objectives for the future, and to identify knowledge gaps in need of scientific inquiry. This two-part review concentrates on CT-CCM as its own subspeciality of critical care and cardiothoracic surgery and provides aspirational goals for its practitioners and scientists. In part one, a list of guiding principles and a call-to-action agenda geared towards growth and promotion of CT-CCM are offered. In part two, an evaluation of selected scientific data is performed, identifying gaps in CT-CCM knowledge, and recommending direction to future scientific endeavors.

Background: The optimal vasopressor management for septic patients with left ventricular (LV) dysfunction has not been well established, and current evidence is conflicting regarding the optimal vasopressor discontinuation order., Objective: The objective was to evaluate the impact of LV dysfunction on the hemodynamic management of septic shock by assessing the incidence of clinically significant hypotension after vasopressor discontinuation., Methods: In this single-center, retrospective cohort study, adult patients were included if they met the Sepsis-3 definition of septic shock, had LV dysfunction (defined as an ejection fraction ≤40%), and received norepinephrine and vasopressin as the last vasopressors discontinued. The primary outcome was the incidence of clinically significant hypotension following discontinuation of vasopressin or norepinephrine. Clinically significant hypotension was defined as a MAP less than 60 mmHg and the need for either: 1) the reinstitution of the previously discontinued agent at any dosage, 2) the receipt of at least 500 mL of a crystalloid at a rate of at least 500 mL/hour, 3) or the receipt of at least 25 grams of albumin 5% at a rate of at least 25 gram/hour. Secondary outcomes included intensive care unit (ICU) and hospital lengths of stay, and ICU and hospital mortality., Results: A total of 78 patients met inclusion criteria, with 37 patients having vasopressin discontinued first and 41 having norepinephrine discontinued first. Clinically significant hypotension occurred in 28 patients (76%) following the discontinuation of vasopressin, compared to 28 patients (81%) following the discontinuation of norepinephrine (p = 0.61). ICU length of stay was 9 days in the vasopressin discontinued first cohort, compared to 15 days in the norepinephrine discontinued first cohort (p = 0.01). There was no statistically significant difference in mortality observed., Conclusion: The discontinuation order of norepinephrine and vasopressin did not impact the incidence of clinically significant hypotension in patients with septic shock and LV dysfunction, but may influence ICU length of stay, although other factors may have impacted this finding.

Fragment-based drug design relies heavily on structural information for the elaboration and optimisation of hits. The ability to identify neighbouring binding hot spots, energetically favourable interactions and conserved binding motifs in protein structures through X-ray crystallography can inform the evolution of fragments into lead-like compounds through structure-based design. The composition of fragment libraries can be designed and curated to fit this purpose and herein, we describe and compare screening libraries containing compounds comprising between 2 and 18 heavy atoms. We evaluate the properties of the compounds in these libraries and assess their ability to probe protein surfaces for binding hot spots., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Competing Interests: Conflict of Interest None.

Objective: Neurocutaneous syndromes have variable multisystem involvement. The multiorgan involvement, potential pathologies, and various treatment options necessitate collaboration and open discussion to ensure optimal treatment in any given patient. These disorders provide quintessential examples of chronic medical conditions that require a lifelong, multidisciplinary approach. The objectives of this study were to 1) perform a systematic review, thoroughly assessing different multidisciplinary clinic layouts utilized in centers worldwide; and 2) characterize an institutional experience with the management of these conditions, focusing on the patient demographics, clinical presentation, complications, and therapeutic strategies seen in a patient population., Methods: A systematic review of studies involving multidisciplinary clinics and their reported structure was performed according to PRISMA guidelines using the PubMed database. Then a retrospective chart review of patients enrolled in the Oklahoma Children's Hospital Neurocutaneous Syndromes Clinic was conducted., Results: A search of the PubMed database yielded 251 unique results. Of these, 15 papers were included in the analysis, which identified 16 clinics that treated more than 2000 patients worldwide. The majority of these clinics treated patients with neurofibromatosis (13/16). The remaining clinics treated patients with von Hippel-Lindau syndrome (n = 1), tuberous sclerosis complex (n = 1), and multiple neurocutaneous syndromes (n = 1). The most commonly represented subspecialties in these clinics were genetics (15/16) and neurology (13/16). Five clinics (31%) solely saw pediatric patients, 10 clinics saw a combination of children and adults, and the final clinic had separate pediatric and adult clinics. The retrospective chart review of the Neurocutaneous Syndromes Clinic demonstrated that 164 patients were enrolled and seen in the clinic from April 2013 to December 2021. Diagnoses were made based on clinical findings or results of genetic testing; 115 (70%) had neurofibromatosis type 1, 9 (5.5%) had neurofibromatosis type 2, 35 (21%) had tuberous sclerosis complex, 2 (1%) had von Hippel-Lindau syndrome, 2 (1%) had Gorlin syndrome, and the remaining patient (0.6%) had Aarskog-Scott syndrome. Patient demographics, clinical presentation, complications, and therapeutic strategies are also discussed., Conclusions: To the best of the authors' knowledge, this is the first detailed description of a comprehensive pediatric neurocutaneous clinic in the US that serves patients with multiple syndromes. There is currently heterogeneity between described multidisciplinary clinic structures and practices. More detailed accounts of clinic compositions and practices along with patient data and outcomes are needed in order to establish the most comprehensive and efficient multidisciplinary approach for neurocutaneous syndromes.

Background: Partial trisomy of the long arm of chromosome 11 is a rare cytogenetic abnormality. It has been characterized by variable sized duplications that lead to a range of phenotypes including growth retardation, developmental delay/intellectual disability, and distinctive craniofacial abnormalities. Congenital heart defects, skeletal abnormalities, urogenital anomalies, and hypotonia are found in some affected individuals., Methods: We describe a 16-year-old patient presented with most of the hallmark phenotypes of trisomy 11q syndrome as well as exhibiting symptoms of hearing loss, seizures, and abnormal endocrinological and ophthalmological findings. Routine chromosome analysis and subsequent chromosomal microarray analysis (CMA) were performed to detect genetic abnormalities in this patient., Results: We identified an abnormal male karyotype with a derivative chromosome 4 due to an unbalanced translocation between chromosomes 4 and chromosome 11. The CMA results revealed a 56 Mb duplication of chromosome 11q14.1-qter and a 874 Kb terminal deletion of the short arm of chromosome 4., Conclusion: A genomic imbalance resulting in partial trisomy 11q was found in a patient with multiple congenital anomalies. We compared the phenotypes of all known "pure" trisomy 11q cases in the literature and find that trisomy 11q23-qter is both recurrent and the most common cytogenetic abnormality found in the reported cases. It is associated with the core features of trisomy 11q syndrome., (© 2022. The Author(s).)

Background: Enoxaparin is the recommended agent for deep vein thrombosis (DVT) chemoprophylaxis in trauma patients. Current literature suggests weight-based dosing is superior to standard dosing for adequate chemoprophylaxis. Literature regarding the use of weight-based enoxaparin in the setting of traumatic brain injury (TBI) however is limited., Methods: A retrospective analysis of adult trauma patients admitted between January 1, 2018 to February 28, 2019 was performed. Sixty-six patients with TBI receiving weight-based enoxaparin met inclusion criteria. Incidence of intracranial hemorrhage (ICH) expansion was the primary endpoint. Newly diagnosed venous thromboembolism (VTE) and death were secondary endpoints., Results: Two patients, out of sixty-six, had progression of their TBI requiring surgical intervention. Newly diagnosed VTE occurred in one patient. No deaths were due to ICH expansion or VTE., Conclusions: Use of weight-based enoxaparin dosing in the setting of TBI shows promise without an increased incidence of ICH expansion when compared to other studies. Level of Evidence and Study Type: Level IV, Therapeutic., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Parents serve as role models and household policy makers for their children's home social environment. Also, parents may influence the home physical environment through the provision of resources to support their children's dietary, activity, and sleep behaviors. Understanding the parental characteristics related to children's home environment may allow for tailoring obesity interventions to families' needs. This study aimed to explore parental qualities (general parenting styles, parent feeding practices, and parental BMI) related to healthy home food, physical activity, media and sleep environment of toddlers. A total of 50 multi-ethnic parents with toddler age children who were enrolled in a randomized pilot study of a wellness program completed the Structure and Control in Parent Feeding (SCPF) questionnaire and Comprehensive General Parenting Questionnaire (CGPQ). Parental BMI was calculated using self-reported weight and height data. The Healthy Home Survey, the Home Food Inventory, the Sleep Environment Questionnaire, and items developed for this study were standardized and summed to create home food, physical activity, screen media, and sleep environment scores; high scores reflected healthier environments. To examine the relationships between parental qualities and the home environment, Pearson's correlation test was performed. Parental BMI and overall healthy home environment were inversely associated (r = -0.306; p = 0.032). Structure in general parenting and parental feeding practice were positively correlated with the overall healthy home environment (r = 0.336; p = 0.026) and healthy home food environment (r = 0.415; p = 0.003), respectively. The coercive control general parenting was inversely related to overall healthy home environment score (r = -0.333; p = 0.022). Based on the findings from this study, parents who provide clear communication, set consistent rules, avoid pressure to control their child's behavior, and have lower BMI tend to live in a home environment that support children's health behaviors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: This global survey of experts assessed the suitability of different health-related interventions for inclusion in school health services (SHSs) to inform development of the World Health Organization global guideline on SHSs., Methods: A review of 138 global World Health Organization publications identified 406 health service interventions for 5- to 19-year-old individuals. These were consolidated, pretested, and pilot-tested in a questionnaire as 86 promotion, prevention, care, or treatment interventions. A total of 1,293 experts were identified through purposive sampling of journal databases and professional networks. In July 2019, experts were invited to complete the questionnaire online in Arabic, Chinese, English, French, Russian, or Spanish. Respondents categorized each intervention as essential, highly suitable, suitable, or unsuitable in SHSs (everywhere or in certain geographic areas only). They could also suggest interventions., Results: Interventions categorized most often as "Essential in SHSs everywhere" (70%-80%) are related to health promotion and health education. Clinical interventions categorized most often in this way (60%-68%) are related to immunization, screening, assessment, and general care. Interventions categorized most often as "Essential in SHSs in certain geographic areas only" (27%-49%) are related to immunization, mass drug administration, and health promotion. Interventions categorized most often as "Unsuitable in SHSs anywhere" (12%-14%) are related to screening of noncommunicable conditions. There were no important regional differences. Of 439 respondents from 81 countries, 188 suggested 378 additional interventions. Question order effect and/or purposive sampling biases may have influenced both quantitative and qualitative results for different types of intervention., Conclusions: Favorable responses to almost all interventions supported their World Health Organization guideline inclusion but provided little guidance for intervention prioritization., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: There are a growing number of older adults with combined age-related vision loss (ARVL) and dementia. Existing literature shows the pervasive impact that both diagnoses have separately on the participation of older adults, however, little is known about the societal participation of older adults with both conditions. As such, the aim of this scoping review was to explore the combined impact of ARVL and dementia on the participation of older adults, with a specific focus on highlighting strategies that help mitigate the impact of ARVL and dementia on participation., Methods: This study utilized a scoping review, informed by the framework by Arksey and O'Malley [1]. Two researchers independently ran a total of 62 search terms across four categories in six databases (PubMed, CINAHL, Scopus, Embase, Medline, PsycINFO), with an initial yield of 2,053 articles. Grey literature was also included in this scoping review and was retrieved from organizational websites, brochures, conference proceedings, and a Google Scholar search. The application of study inclusion criteria resulted in a final yield of 13 empirical studies and 10 grey literature sources., Results: Following detailed thematic analysis of the empirical and grey literature sources, four themes emerged regarding the impact of combined ARVL and dementia on the participation of older adults including: 1) Managing the pragmatic aspects of a dual diagnosis; 2) Diverse approaches to risk assessment and management; 3) Adopting a multi-disciplinary approach to facilitate care and; 4) Using compensatory strategies to facilitate participation., Conclusions: The four themes highlight the challenges older adults with these combined diagnoses experience, which limit their opportunities for meaningful participation. Given the scarcity of research on this topic, future research should identify the type of ARVL and dementia diagnoses of study participants, conduct qualitative research about the lived experiences of older adults with a dual diagnosis, and broaden the geographic scope of research., Competing Interests: The authors have declared that no competing interests exist.

Purpose/Background: Percutaneous left ventricular assist devices (pVADs) require a continuous purge solution containing heparin to prevent pump thrombosis and device failure. Data regarding alternative options in patients who have suspected heparin-induced thrombocytopenia (HIT) are limited. Methods: In this report, we describe a 68-year-old white man with cardiogenic shock with an Impella CP device managed with a low concentration argatroban-based purge solution secondary to a suspected diagnosis of HIT. Results: The purge solution was initiated as argatroban in dextrose 10% at a concentration of 0.12 mg/mL and was subsequently decreased twice to 0.06 and 0.015 mg/mL based on the patient's clinical course. Conclusions: This case report describes the safe and effective use of argatroban purge solution necessary for anticoagulation although further studies are needed to confirm these findings., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Psychiatric medication nonadherence continues to be a leading cause of poor health outcomes for individuals experiencing homelessness. Identifying the sociodemographic factors that contribute to medication nonadherence may help guide strategies to care for and support this group. This study examined 200 adults with depression diagnoses and active anti-depressant prescriptions (Mage = 43.98 ± 12.08, 59.4% Caucasian, 58.5% male, 70% uninsured, 89.5% unemployed) and 181 adults with anxiety diagnoses and active anti-anxiety prescriptions (Mage = 43.45 ± 11.02, 54.4% Caucasian, 57.5% male, 66.3% uninsured, 88.9% unemployed) recruited from six homeless-serving agencies in Oklahoma City. Self-reported sociodemographic variables included: age, sex, race/ethnicity, education, monthly income, employment status, and health insurance status. Adjusted logistic regression analyses revealed that employed (OR = 4.022, CI 0.95 : 1.244-13.004) and insured (OR = 2.923, CI 0.95 : 1.225-6.973) participants had greater odds of depression medication nonadherence. For anxiety, being employed (OR = 3.573, CI 0.95 : 1.160-11.010) was associated with greater odds of anxiety medication nonadherence, whereas having depression and anxiety diagnostic comorbidity (OR = 0.333, CI 0.95 : 0.137-0.810) was associated with lower odds of anxiety medication nonadherence. Interventions aimed at facilitating accessible prescription acquisition or otherwise reducing barriers to prescription medications for employed adults, including those with health insurance, may benefit adherence, but more research is needed. Future studies would benefit from using a qualitative approach to better delineate nuanced barriers to psychiatric medication adherence.

This study evaluated the feasibility and effects of the Families Understanding Nutrition and Physically Active Lifestyles (FUNPALs) Playgroup on toddler (12-36-month-old) diet and activity behaviors. Parent-toddler dyads were recruited from disadvantaged communities and randomly assigned to receive 10-weekly sessions of the FUNPALs Playgroup ( n = 24) or dose-matched health education control group ( n = 26). FUNPALs Playgroups involved physical and snack activities, delivery of health information, and positive parenting coaching. The control group involved group health education for parents only. Process outcomes (e.g., retention rate, fidelity) and focus groups determined feasibility and perceived effects. To evaluate preliminary effects, validated measures of toddler diet (food frequency questionnaire and a carotenoid biomarker), physical activity (PA; accelerometers), general and feeding parenting (self-report surveys), and home environment (phone interview) were collected pre and post. The sample comprised parents (84% female) who self-identified as Hispanic/Latino (38%) and/or African American (32%). Retention was high (78%). Parents from both groups enjoyed the program and perceived improvements in their children's health behaviors. Objective measures demonstrated improvement with large effects (η 2 = 0.29) in toddler diet ( p < 0.001) but not PA ( p = 0.099). In conclusion, the FUNPALs Playgroup is feasible and may improve toddler eating behaviors.

The current study utilized data from the Social Justice Sexuality Project to investigate influences on psychological well-being of LGBT+ Muslims (N = 75) in the United States. Specifically, path analyses were used to examine the association between spiritual and religious engagement, LGBT community involvement, outness, and family support with psychological well-being. Control variables included lifespan Islam involvement, age, income, and the age at which the participant came out to themselves. Findings illustrate spiritual and religious engagement, outness, and income were all positively related to psychological well-being. Moreover, individuals who had converted to Islam but were not raised in the faith had significantly lower psychological well-being than those who had a consistent experience with Islam from their childhood until the time of the study. The present investigation provides critical contributions to the study of gender and sexual minorities in the United States and the experiences of currently practicing LGBT+ Muslims and those who were raised Muslim. Clinical implications and future research suggestions are discussed.

Study Objective: The purpose of this study was to evaluate the utility of routine anti-Xa peak monitoring for trauma patients initiated on weight-based enoxaparin for venous thromboembolism (VTE) prophylaxis and identify patient populations where monitoring is necessary., Design: Retrospective study., Setting: Augusta University (AU) Medical Center in Augusta, Georgia, a level 1 trauma center., Patients: Adult patients admitted to the trauma surgery service requiring chemical VTE prophylaxis., Intervention: At least three consecutive doses of enoxaparin 0.5 mg/kg subcutaneously every 12 hour for VTE prophylaxis prior to an anti-Xa peak as the initial chemical VTE prophylaxis strategy., Measurements: The primary end point was the percentage of patients who achieved goal anti-Xa peak of 0.2-0.6 unit/ml. The incidence of newly diagnosed VTE and clinically significant bleeding were assessed as secondary end points., Main Results: From January 1, 2018, through February 28, 2019, 300 patients met inclusion criteria. Anti-Xa peaks were within goal in 91% of all patients, 7.7% were below goal, and 1.3% were above goal. For patients who did not meet the goal, dose adjustments were made in 70.4% of patients. New levels were obtained in 73.7% of those patients, and all repeat levels was within goal. Clinically significant bleeding occurred in 5.3% of patients. Newly diagnosed VTE occurred in 1.7% of patients., Conclusions: The use of initial weight-based enoxaparin dosing in trauma patients routinely achieved the prespecified target anti-Xa goal. In conclusion, anti-Xa levels are not necessary for routine monitoring of weight-based enoxaparin for VTE prophylaxis in trauma patients. Incidence of clinically significant bleeding and newly diagnosed VTE were similar to previous studies., (© 2021 Pharmacotherapy Publications, Inc.)

Purpose: This study aims to provide a comprehensive description of the phenotypic and genotypic spectrum of SNAP25 developmental and epileptic encephalopathy (SNAP25-DEE) by reviewing newly identified and previously reported individuals., Methods: Individuals harboring heterozygous missense or loss-of-function variants in SNAP25 were assembled through collaboration with international colleagues, matchmaking platforms, and literature review. For each individual, detailed phenotyping, classification, and structural modeling of the identified variant were performed., Results: The cohort comprises 23 individuals with pathogenic or likely pathogenic de novo variants in SNAP25. Intellectual disability and early-onset epilepsy were identified as the core symptoms of SNAP25-DEE, with recurrent findings of movement disorders, cerebral visual impairment, and brain atrophy. Structural modeling for all variants predicted possible functional defects concerning SNAP25 or impaired interaction with other components of the SNARE complex., Conclusion: We provide a comprehensive description of SNAP25-DEE with intellectual disability and early-onset epilepsy mostly occurring before the age of two years. These core symptoms and additional recurrent phenotypes show an overlap to genes encoding other components or associated proteins of the SNARE complex such as STX1B, STXBP1, or VAMP2. Thus, these findings advance the concept of a group of neurodevelopmental disorders that may be termed "SNAREopathies."

The Anecdata website and its corresponding mobile app provide unique features to meet the needs of a wide variety of diverse citizen science projects from across the world. The platform has been developed with the help of continuous feedback from community partners, project leaders, and website users and currently hosts more than 200 projects. Over 8,000 registered users have contributed more than 30,000 images and over 50,000 observations since the platform became open to the public in 2014. From its inception, one of the core tenets of Anecdata's mission has been to make data from citizen science projects freely accessible to project participants and the general public, and in the platform's first few years, it followed a completely open data access model. As the platform has grown, hosting ever more projects, we have found that this model does not meet all project needs, especially where endangered species, property access rights, participant safety in the field, and personal privacy are concerned. We first introduced features for data and user privacy as part of "All About Arsenic," a National Institutes of Health (NIH)/National Institute of General Medical Sciences (NIGMS) Science Education Partnership Award (SEPA)-funded project at MDI Biological Laboratory, which engages middle and high school teachers and students from schools across Maine and New Hampshire in sampling their home well water for analysis of arsenic and other heavy metals. In order to host this project on Anecdata, we developed features for spatial privacy or "geoprivacy" to conceal the coordinates of samplers' homes, partial data redaction tools we call "private fields" to withhold certain sample registration questions from public datasets, and "participant anonymity" to conceal which user account uploaded an observation. We describe the impetus for the creation of these features, challenges we encountered, and our technical approach. While these features were originally developed for the purposes of a public health and science literacy project, they are now available to all project leaders setting up projects on Anecdata.org and have been adopted by a number of projects, including Mass Audubon's Eastern Meadowlark Survey, South Carolina Aquarium's SeaRise, and Coastal Signs of the Seasons (SOS) Monitoring projects., Competing Interests: Conflict of Interest: 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.

Prior research with a sample of male probationers indicates severity levels of one arresting intimate partner violence (IPV) offense are predictive of future frequency of such offenses and treatment completion. This study is an extended analysis looking at severity ratings across two IPV offenses to measure violence stability. The stability of IPV severity levels was analyzed in a sample of offenders in Lake County, Illinois. Offender subtypes of generally violent (GV) men and family only (FO) violent men were incorporated into stability analyses using generalized linear mixed modeling (GLMM) to determine whether certain types of offenders vary in violence levels over time. The purpose was to determine the predictive utility of using a single offense to determine the domestic violence trajectory for male probationers. Reoffense records of 80 men were collected from a larger sample of 352 males, ages 17 to 72 placed on probation in Lake County, Illinois, between 2006 and 2008. Severity of offenses was coded dichotomously based on a behaviorally derived measure. Results demonstrate 64% of reoffenders remained stable in IPV severity. Overall, severity levels decreased across time. This is the first study to use a probationary sample of men to analyze violence stability trends over time. This study confirms the utility of measuring a single offense to predict future violence trajectories for IPV offenders.

Background: Rates of obesity continue to rise worldwide as evidenced in the 2017 Centers for Disease Control and Prevention (CDC) report that indicated over 35% of United States (US) citizens are obese, with Louisiana ranked as the fifth most obese state in America. Since large clinical trials tend to exclude obese patients, health care providers are faced with concerns of under- or overdosing these patients on warfarin., Methods: This retrospective chart review evaluated patients who reported to a community anticoagulation clinic for warfarin management between 1 June 2017 and 30 September 2017. Along with baseline demographics, chronic use of drugs that have clinically significant interactions with warfarin, social activity such as tobacco use and alcohol consumption, were collected. Body mass indexes (BMI) were collected and categorized according to the World Health Organization definitions as follows: Normal (BMI 18-24.9 kg/m 2 ), Overweight (25-29.9 kg/m 2 ), Obesity Class I (30-34.9 kg/m 2 ), Obesity Class II (35-39.9 kg/m 2 ), Obesity Class III (⩾40 kg/m 2 ). The primary outcome was the mean 90-day warfarin dose required to maintain "intermediate control" or "good control" of international normalized ratio (INR), stratified by BMI classifications. The secondary outcome was the time in therapeutic range (TTR) stratified by BMI classifications., Results: A total of 433 patient encounters were included in this study. There was a total of 43 encounters in the Normal BMI category, 111 Overweight encounters, 135 Obesity Class I encounters, 45 Obesity Class II encounters, and 99 Obesity Class III encounters. Approximately 63% of the study population were male, and over 90% the patients were African American. The Obesity Class I and Obesity Class II class required an average of 11.47 mg and 17.10 mg more warfarin, respectively, to maintain a therapeutic INR when compared with the Normal BMI category. These findings were statistically significant with p values of 0.007 and <0.001, respectively. Additionally, upon comparing the Overweight BMI category with the Obesity Class II category, there was a mean warfarin dose difference of 11.22 mg ( p  = 0.010) more in Obesity Class II encounters to maintain a therapeutic INR. In the secondary analysis of TTR, Overweight category encounters had the highest TTR, whereas encounters in the Normal BMI category had the lowest TTR., Conclusion: As BMI increases, there is an increased chronic warfarin requirement to maintain "intermediate control" or "good control" of INR between 2 and 3 in an ambulatory care setting.

The presence of suitable cavities or pockets on protein structures is a general criterion for a therapeutic target protein to be classified as 'druggable'. Many disease-related proteins that function solely through protein-protein interactions lack such pockets, making development of inhibitors by traditional small-molecule structure-based design methods much more challenging. The 22 kDa bacterial thiol oxidoreductase enzyme, DsbA, from the gram-negative bacterium Burkholderia pseudomallei (BpsDsbA) is an example of one such target. The crystal structure of oxidized BpsDsbA lacks well-defined surface pockets. BpsDsbA is required for the correct folding of numerous virulence factors in B. pseudomallei, and genetic deletion of dsbA significantly attenuates B. pseudomallei virulence in murine infection models. Therefore, BpsDsbA is potentially an attractive drug target. Herein we report the identification of a small molecule binding site adjacent to the catalytic site of oxidized BpsDsbA. 1 H N CPMG relaxation dispersion NMR measurements suggest that the binding site is formed transiently through protein dynamics. Using fragment-based screening, we identified a small molecule that binds at this site with an estimated affinity of K D  ~ 500 µM. This fragment inhibits BpsDsbA enzymatic activity in vitro. The binding mode of this molecule has been characterized by NMR data-driven docking using HADDOCK. These data provide a starting point towards the design of more potent small molecule inhibitors of BpsDsbA.