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Breast cancer is the second leading cause of death in women globally, and it remains a health burden due to poor therapy response, cancer cell drug resistance, and the debilitating side effects associated with most therapies. One approach to addressing the need to improve breast cancer therapies has been to elucidate the mechanism(s) underpinning this disease to identify key drivers that can be targeted in molecular therapies. The T-box transcription factor, TBX3, is upregulated in breast cancer, in which it contributes to important oncogenic processes, and it has been validated as a potential therapeutic target. Here, we investigated the molecular mechanisms that upregulate TBX3 in breast cancer, and we show that it involves transcriptional activation by c-Myc, post-translational modification by AKT1 and AKT3, and interaction with the molecular chaperone Hsc70. Together, the results from this study provide evidence that c-Myc, AKT, Hsc70, and TBX3 form part of an important oncogenic pathway in breast cancer and thus reveal versatile ways of interfering with the oncogenic activity of TBX3 for the treatment of this neoplasm. Implications: Targeting the c-Myc/AKT/TBX3/Hsc70 signaling axis may be an effective treatment strategy for TBX3-driven breast cancer., (©2024 American Association for Cancer Research.)

Introduction: The overdose crisis in the U.S. disproportionately impacts people experiencing homelessness. Permanent supportive housing (PSH) - permanent, affordable housing with voluntary support services - is an effective, evidence-based intervention to address homelessness. However, overdose risk remains high even after entering PSH for individual and structural reasons. In this study, we aimed to refine a set of evidence-based overdose prevention practices (EBPs) and an associated implementation support package for PSH settings using focus groups with PSH tenants, frontline staff, and leaders., Methods: Our community-academic team identified an initial set of overdose EBPs applicable for PSH through research, public health guidance, and a needs assessment. We adapted these practices based on feedback from focus groups with PSH leaders, staff, and tenants. Focus groups followed semi-structured interview guides developed using the EPIS (Exploration, Preparation, Implementation, Sustainment) framework constructs of inner context, outer context, and bridging factors related to overdose prevention and response., Results: We conducted 16 focus groups with 40 unique participants (14 PSH tenants, 15 PSH staff, 11 PSH leaders); focus groups were held in two iterative rounds and individuals could participate in one or both rounds. Participants were diverse in gender, race, and ethnicity. Focus group participants were enthusiastic about the proposed EBPs and implementation strategies, while contributing unique insights and concrete suggestions to improve upon them. The implementation support package contains an iteratively refined PSH Overdose Prevention (POP) Toolkit with 20 EBPs surrounding overdose prevention and response, harm reduction, and support for substance use treatment and additional core implementation strategies including practice facilitation, tenant-staff champion teams, and learning collaboratives., Conclusions: This manuscript describes how robust community-academic partnerships and input from people with lived experience as tenants and staff in PSH informed adaptation of evidence-based overdose prevention approaches and implementation strategies to improve their fit for PSH settings. This effort can inform similar efforts nationally in other settings serving highly marginalized populations. We are currently conducting a randomized trial of the refined overdose prevention implementation support package in PSH., Competing Interests: Declaration of competing interest The authors do not report any competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Social determinants of health have been shown to influence individual mental health and overall well-being. Additionally, populations that experience stigma and/or discrimination because of race, class, gender, or another identity group experience disproportionately higher rates of mental health disorders than populations that do not experience such marginalization. One way to address upstream social determinants that influence mental health is through systems change initiatives. In 2019, Indiana implemented a statewide Regional Prevention System (RPS) focused on systems change to promote mental health and prevent substance misuse., Methods: We developed a semi-structured interview guide to collect insights about the RPS implementation and sustainability. Potential participants were identified based on their role as an active regional coordinator (n = 9). We conducted qualitative interviews with all 9 regional coordinators in Indiana. Interview recordings were transcribed and coded using an a priori coding framework based on constructs from the Theory of Innovation Implementation and the Consolidated Framework for Implementation Research., Results: Insights about the RPS implementation process are presented across four domains: innovation, system-level, organization-level, and sustainability. In terms of implementation barriers, coordinators encountered hesitancy and distrust from community members, which they had to overcome to gain buy-in. They also described stigma, including community and individual social norms towards mental health and substance misuse, as barriers that challenged efforts to engage community members in the RPS. Facilitators of implementation included having established community infrastructure and external partnerships. In communities without existing infrastructure to support prevention efforts, particularly rural communities, the implementation process took longer but community members welcomed the additional support and valued the new communication platforms created by the RPS. On sustainability, coordinators provided examples of communities that were able to obtain grant funding in support of prevention initiatives launched through the RPS., Conclusion: The process of implementing and sustaining prevention efforts through the RPS varied across communities. Prioritizing the delivery of systems-change efforts in underserved communities that are ready for change, rather than statewide efforts, may offer a better strategy for addressing disparities in the social determinants of health that influence mental health and substance misuse., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Review Board (IRB) at Indiana University (IRB#21864). The IRB determined this study to be exempt under Category 2: interaction involving educational tests, surveys, interviews, or observation of public behavior & would not reasonably place subjects at risk. All participants received a study information sheet prior to participation and provided verbal consent to be recorded at the start of the interview. Consent for publication: Not applicable. Competing interests: Dr. Burns has previously served as a regional coordinator and received compensation from the Indiana Division of Mental Health and Addiction (DMHA) for work performed in Marion County, IN (excluded from this study). At the time of this study, Dr. Burns was no longer in this role and no longer receiving any personal compensation from DMHA., (© 2024. The Author(s).)

Competing Interests: The author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

Competing Interests: The author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

Background: Rising health care costs and consequent increases in Medicare reimbursements have led to many payment reforms over the years. Implementation of the prospective payment system (PPS) for hospitals in 1983 incentivized hospitals to either purchase skilled nursing facilities (SNFs) or utilize their excess capacity to establish one within the hospital. With PPS reimbursement being applied to SNFs in 1998, prior monetary incentives for hospitals to own an SNF disappeared. However, despite the reduction in numbers, many hospitals continued to operate their hospital-based skilled nursing facilities (HBSNFs)., Purpose: This study examines the organizational and market-level factors associated with the survival of HBSNFs using the population ecology of organizations framework., Methodology: Using American Hospital Association survey data, event histories of all U.S. acute care hospitals with an open HBSNF in 1998 were plotted to examine if a hospital closed its HBSNF during a 22-year period (1998-2020). The primary independent variables included hospital size, ownership, total margin, market competition, and Medicare Advantage penetration. The independent and control variables were lagged by 1 year. Cox regressions were conducted to estimate the hazard ratios capturing the risk of HBSNF closure., Results: The results showed that HBSNFs located in large, not-for-profit hospitals and those operating in less competitive markets had greater odds of surviving., Practice Implications: The HBSNF administrators of small, for-profit hospitals and those operating in highly competitive markets could utilize the findings of this study to judiciously allocate slack resources to their HBSNFs to keep those open given the current emphasis on continuity of care by regulatory bodies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This scoping review aimed to identify and summarise evidence on the comfort and functional performance of police officer personal protective equipment (PPE). The Arksey and O'Malley (2005) five-stage framework for scoping reviews was followed. PubMed, CINAHL, Scopus, and Web of Science were searched, and 35 articles were included in the review. The findings show that increased police PPE mass increases heart rate, metabolic energy expenditure, and perceived exertion in response to exercise. Unisex armour designs cause increased discomfort for females with larger bra sizes. PPE reduces joint-specific range of motion, with the design and location impairing movement more than mass. Jumping and sprinting performance is decreased with heavy PPE but unaffected by lighter protection, while agility is compromised with most forms of protection. Future research is needed on the fit and function of PPE for specialist police units, such as mounted police, along with further investigations on how fit can affect functional performance.

Density-dependent competition for food influences the foraging behaviour and demography of colonial animals, but how this influence varies across a species' latitudinal range is poorly understood. Here we used satellite tracking from 21 Northern Gannet Morus bassanus colonies (39% of colonies worldwide, supporting 73% of the global population) during chick-rearing to test how foraging trip characteristics (distance and duration) covary with colony size (138-60 953 breeding pairs) and latitude across 89% of their latitudinal range (46.81-71.23° N). Tracking data for 1118 individuals showed that foraging trip duration and maximum distance both increased with square-root colony size. Foraging effort also varied between years for the same colony, consistent with a link to environmental variability. Trip duration and maximum distance also decreased with latitude, after controlling for colony size. Our results are consistent with density-dependent reduction in prey availability influencing colony size and reveal reduced competition at the poleward range margin. This provides a mechanism for rapid population growth at northern colonies and, therefore, a poleward shift in response to environmental change. Further work is required to understand when and how colonial animals deplete nearby prey, along with the positive and negative effects of social foraging behaviour., Competing Interests: We declare we have no competing interests., (© 2024 The Author(s).)

Keloid disease (KD) is a common connective tissue disorder of unknown aetiopathogenesis with ill-defined treatment. Keloid scars present as exophytic fibroproliferative reticular lesions postcutaneous injury, and even though KD remains neoplastically benign, keloid lesions behave locally aggressive, invasive and expansive. To date, there is limited understanding and validation of biomarkers identified through combined proteomic and genomic evaluation of KD. Therefore, the aim in this study was to identify putative causative candidates in KD by performing a comprehensive proteomics analysis of subcellular fractions as well as the whole cell, coupled with transcriptomics data analysis of normal compared with KD fibroblasts. We then applied novel integrative bioinformatics analysis to demonstrate that NF-kB-p65 (RELA) from the cytosolic fraction and CAPN2 from the whole-cell lysate were statistically significantly upregulated in KD and associated with alterations in relevant key signaling pathways, including apoptosis. Our findings were further confirmed by showing upregulation of both RELA and CAPN2 in KD using flow cytometry and immunohistochemistry. Moreover, functional evaluation using real-time cell analysis and flow cytometry demonstrated that both omeprazole and dexamethasone inhibited the growth of KD fibroblasts by enhancing the rate of apoptosis. In conclusion, subcellular fractionation and metaproteogenomic analyses have identified, to our knowledge, 2 previously unreported biomarkers of significant relevance to keloid diagnostics and therapeutics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Patient data is subject to missingness and errors. Patient portals enable patients managing type 2 diabetes mellitus (T2DM) to review and correct data to avoid retesting, medication errors, and diagnostic mistakes. We examined whether patient portal use was associated with electronic health record (EHR) data timeliness in T2DM care., Research Design and Methods: We analyzed EHR data from a panel of adult patients to determine whether portal use improved data timeliness. EHR data timeliness is measured as the number of days between patient encounters, accounting for mean attribute update periods, where available EHR attribute updates for T2DM measurements were present, including body mass, weight, glycated hemoglobin A1c, cholesterol, blood pressure, serum creatinine, and smoking status. We performed negative binomial regressions with fixed effects to estimate the association between patient portal use and EHR data timeliness. Sensitivity analyses were conducted using Poisson regressions., Results: Nearly a third (31.3%) of patients in our sample actively used the health portal. There were fewer days (111.9 days vs. 136.7 days; p  < 0.001) between EHR attribute updates for patients who used health portals compared to patients who did not. Data timeliness was lower among female, non-Hispanic White Medicare beneficiaries. Based on regression analyses, portal use was associated with an expected 3.6 ( p  < 0.001) percentage point decrease in days between attribute updates, indicating improved EHR timeliness., Conclusion: Improving the quality of health information may streamline decision-making in partnership with patients who produce data points across clinical settings. Active use of patient portals and digital health tools in chronic disease care are critical for care management and clinical decision-making, especially for patients managing type 2 diabetes across clinical settings., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01468-6., Competing Interests: Conflict of interestThe authors of this study have no relevant financial or non-financial interests to disclose., (© The Author(s) 2024.)

Neonatal sepsis remains one of the leading causes of mortality in newborns. Several brainstem-regulated physiological processes undergo disruption during neonatal sepsis. Mechanistic knowledge gaps exist at the interplay between metabolism and immune activation to brainstem neural circuits and pertinent physiological functions in neonates. To delineate this association, we induced systemic inflammation either by TLR4 (LPS) or TLR1/2 (PAM3CSK4) ligand administration in postnatal day 5 mice (PD5). Our findings show that LPS and PAM3CSK4 evoke substantial changes in respiration and metabolism. Physiological trade-offs led to hypometabolic-hypothermic responses due to LPS, but not PAM3CSK4, whereas to both TLR ligands blunted respiratory chemoreflexes. Neuroinflammatory pathways modulation in brainstem showed more robust effects in LPS than PAM3CSK4. Brainstem neurons, microglia, and astrocyte gene expression analyses showed unique responses to TLR ligands. PAM3CSK4 did not significantly modulate gene expression changes in GLAST-1 positive brainstem astrocytes. PD5 pups receiving PAM3CSK4 failed to maintain a prolonged metabolic state repression, which correlated to enhanced gasping latency and impaired autoresuscitation during anoxic chemoreflex challenges. In contrast, LPS administered pups showed no significant changes in anoxic chemoreflex. Electrophysiological studies from brainstem slices prepared from pups exposed to either TLR4 or PAM3CSK4 showed compromised transmission between preBötzinger complex and Hypoglossal as an exclusive response to the TLR1/2 ligand. Spatial gene expression analysis demonstrated a region-specific modulation of PAM3CSK4 within the raphe nucleus relative to other anatomical sites evaluated. Our findings suggest that metabolic changes due to inflammation might be a crucial tolerance mechanism for neonatal sepsis preserving neural control of breathing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: FRMD5 variants were recently identified in patients with developmental delay, ataxia, and eye movement abnormalities., Objectives: We describe 2 patients presenting with childhood-onset ataxia, nystagmus, and seizures carrying pathogenic de novo FRMD5 variants. Weighted gene co-expression network analysis (WGCNA) was performed to gain insights into the function of FRMD5 in the brain., Methods: Trio-based whole-exome sequencing was performed in both patients, and CoExp web tool was used to conduct WGCNA., Results: Both patients presented with developmental delay, childhood-onset ataxia, nystagmus, and seizures. Previously unreported findings were diffuse choreoathetosis and dystonia of the hands (patient 1) and areas of abnormal magnetic resonance imaging signal in the white matter (patient 2). WGCNA showed that FRMD5 belongs to gene networks involved in neurodevelopment and oligodendrocyte function., Conclusions: We expanded the phenotype of FRMD5-related disease and shed light on its role in brain function and development. We recommend including FRMD5 in the genetic workup of childhood-onset ataxia and nystagmus. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

A One Health lens is increasingly significant to address the intertwined challenges in planetary health concerned with the health of humans, nonhuman animals, plants, and ecosystems. A One Health approach can benefit the public health systems in Africa that are overburdened by noncommunicable, infectious, and environmental diseases. Notably, the COVID-19 pandemic revealed the previously overlooked two-fold importance of pharmacogenetics (PGx), for individually tailored treatment of noncommunicable diseases and environmental pathogens. For example, dyslipidemia, a common cardiometabolic risk factor, has been identified as an independent COVID-19 severity risk factor. Observational data suggest that patients with COVID-19 infection receiving lipid-lowering therapy may have better outcomes. However, among African patients, the response to these drugs varies from patient to patient, pointing to the possible contribution of genetic variation in important pharmacogenes. The PGx of lipid-lowering therapies may underlie differences in treatment responses observed among dyslipidemia patients as well as patients comorbid with COVID-19 and dyslipidemia. Genetic variations in APOE, ABCB1, CETP, CYP2C9, CYP3A4, CYP3A5, HMGCR, LDLR, NPC1L1, and SLCO1B1 g enes affect the pharmacogenomics of statins, and they have individually been linked to differential responses to dyslipidemia and COVID-19 treatment. African populations are underrepresented in PGx research. This leads to poor accounting of additional diverse genetic variants that could be important in understanding interindividual and between-population variations in therapeutic responses to dyslipidemia and COVID-19. This expert review examines and synthesizes the salient and priority PGx variations, as seen through a One Health lens in Africa, to improve and inform personalized medicine in both dyslipidemia and COVID-19.

Health literacy is associated with health behaviors and outcomes. Using Andersen's Behavioral Model of Health Services Use, this study examined the role of limited English proficiency (LEP) and social support for the health literacy of Korean American immigrant women, one of the most affected groups by LEP. Researchers surveyed 232 Korean American immigrant women in a metro area in a Southeastern state, U.S. Health literacy was measured by the CDC Behavioral Risk Factor Surveillance System Questionnaire and the California Health Interview Survey. Participants with better English proficiency and larger social support had higher health literacy. LEP and social support interaction was significantly associated with health literacy, illustrating social support as a buffer that mitigates the negative impact of LEP on health literacy. Community programs that enhance social support through community health advocates or peer educators may increase health literacy and reduce health disparities among Korean American immigrant women with LEP.

Background and Objectives: Data on urinary tract infections (UTIs) in very preterm neonates (VPTNs) are scarce. We aimed to (i) describe the characteristics of UTIs in VPTNs and (ii) compare the diagnostic practices of neonatal clinicians to established pediatric guidelines., Methods: All VPTNs (<29 weeks GA) with a suspected UTI at the CHU Sainte-Justine neonatal intensive care unit from January 1, 2014, and December 31, 2019, were included and divided into two definition categories: Possible UTI, and Definite UTI., Results: Most episodes were Possible UTI (87%). Symptoms of UTIs and pathogens varied based on the definition category. A positive urinalysis was obtained in 25%. Possible UTI episodes grew 2 organisms in 62% of cases and <50,000 CFU/mL in 62% of cases., Conclusion: Characteristics of UTIs in VPTNs vary based on the definition category and case definitions used by clinicians differ from that of established pediatric guidelines., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Aim: This systematic review aimed to identify the needs and preferences for cancer care services among Australian First Nations people., Design: Integrative review., Data Sources: An integrative review was conducted. A wide range of search terms were used to increase the sensitivity and specificity of the searches in electronic databases. Methodological quality assessment, data extraction, was conducted independently by two reviewers, and a narrative synthesis was conducted., Results: Forty-two studies were included. A total of 2965 Australian First Nations adults, both men and women of various ages across the lifespan, were represented; no First Nations children affected by cancer were represented in the studies. Three themes emerged which included: (1) discrimination, racism and trauma, resulting from colonization, directly impacted First National people's cancer care experience; (2) cultural ways of knowing, being and doing are fundamental to how First Nations people engage with cancer care services; and (3) First Nations people need culturally safe person-centred cancer care services that address practical needs., Conclusion: Most participants represented in this review experienced discrimination, racism and trauma, resulting from colonization, which directly negatively impacted Aboriginal peoples' cancer care experience. While the Optimal Cancer Pathway (OCP) was launched in Australia several years ago, people with cancer may continue to experience distressing unmet care needs., Patient or Public Contribution: Our team includes both First Nations people, non-First Nations researchers and healthcare professionals with expertise in cancer care. The researchers employed decolonizing restorative approaches to ensure voice, respect, accountability and reciprocity in this review work., Implications for Nursing Practice: Members of the multidisciplinary team including nurses and policymakers should reflect on these findings, ensure that they have up-to-date cultural safety training and stand together with Indigenous and non-Indigenous cancer leaders to take proactive steps to stamp out and dismantle oppression in health, and safely implement the OCP., (© 2023 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Inorganic arsenic (iAs) causes cancer by initiating dynamic transitions between epithelial and mesenchymal cell phenotypes. These transitions transform normal cells into cancerous cells, and cancerous cells into metastatic cells. Most in vitro models assume that transitions between states are binary and complete, and do not consider the possibility that intermediate, stable cellular states might exist. In this paper, we describe a new, two-hit in vitro model of iAs-induced carcinogenesis that extends to 28 weeks of iAs exposure. Through week 17, the model faithfully recapitulates known and expected phenotypic, genetic, and epigenetic characteristics of iAs-induced carcinogenesis. By 28 weeks, however, exposed cells exhibit stable, intermediate phenotypes and epigenetic properties, and key transcription factor promoters (SNAI1, ZEB1) enter an epigenetically poised or bivalent state. These data suggest that key epigenetic transitions and cellular states exist during iAs-induced epithelial-to-mesenchymal transition (EMT), and that it is important for our in vitro models to encapsulate all aspects of EMT and the mesenchymal-to-epithelial transition (MET). In so doing, and by understanding the epigenetic systems controlling these transitions, we might find new, unexpected opportunities for developing targeted, cell state-specific therapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: The author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

Purpose: To compile the literature on the effects of rural hospital closures on the community and summarize the evidence, specifically the health and economic impacts, and identify gaps for future research., Methods: A systematic review of the relevant peer-reviewed literature, published from January 2005 through December 2021, included in the EMBASE, CINAHL, PubMed, EconLit, and Business Source Complete databases, as well as "gray" literature published during the same time period. A total of 21 articles were identified for inclusion., Findings: Over 90% of the included studies were published in the last 8 years, with nearly three-fourths published in the last 4 years. The most common outcomes studied were economic outcomes and employment (76%), emergent, and non-emergent transportation, which includes transport miles and travel time (42.8%), access to and supply of health care providers (38%), and quality of patient outcomes (19%). Eighty-nine percent of the studies that examined economic impacts found unfavorable results, including decreased income, population, and community economic growth, and increased poverty. Between 11 and 15.7 additional minutes were required to transport patients to the nearest emergency facility after closures. A lack of consistency in measures and definition of rurality challenges comparability across studies., Conclusions: The comprehensive impact of rural hospital closures on communities has not been well studied. Research shows predominantly negative economic outcomes as well as increased time and distance required to access health care services. Additional research and consistency in the outcome measures and definition of rurality is needed to characterize the downstream impact of rural hospital closures., (© 2023 The Authors. The Journal of Rural Health published by Wiley Periodicals LLC on behalf of National Rural Health Association.)

Introduction: The proper use of antimicrobials is a challenge in healthcare establishments., Objectives: Describe the detailed antimicrobial consumption profile in 2021-2022. Describe the annual evolutionary profile of the use of antimicrobials in days of therapy/1000 patient days, antibiotic spectrum index/1000 patients days and according to the proportion of days of therapy administered by parenteral route from 2005-2006 to 2021-2022., Method: Descriptive and retrospective study. All patients admitted to our mother-child hospital center between April 1, 2005 and March 31, 2022 were included. The study covers the consumption of all antimicrobials through the AWare classification of the World Health Organization and antibiotic spectrum index., Results: A total of 673.9 days of therapy/1000 patients days was calculated in 2021-2022, i.e. 550.8 for antibiotics, 46.5 for antivirals, 67.9 for antifungals and 8.7 for others. A total of 2436 ASI/1000 patient days was calculated in 2021-2021. According to the AWaRe classification, in 2021-2022, 52.1% (287/551) of days of therapy/1000 patients days referred to the "Access" group, 47.8% (263/551) to the "Watch" group and 0.2% (1/551) to the "Reserve" group., Conclusion: This study aims to explore the use of antimicrobials in a mother-child hospital center. It puts into perspective a stable or even slightly decreasing use of a selection of antimicrobials and compares favorably with published data. Antibiotic governance is based in particular on the periodic evaluation of consumption. Our study illustrates different approaches to quantify and describe this use., (Copyright © 2023. Published by Elsevier Masson SAS.)

Experiencing bereavement as a child or young person (CYP) can have long-lasting effects. The societal and environmental burdens of the SARS-CoV-2 pandemic exacerbated the experience of loss and grief for many CYP, who were unable to access their usual the support networks. However, it is still unclear what is currently known and not known about the experiences of CYP bereaved during the SARS-CoV-2 pandemic. This review used the framework of Arksey and O'Malley and included five stages: (1) identifying the research question; (2) identifying relevant studies; (3) study selection; (4) charting the data; (5) collating, summarizing, and reporting the results. The methodological quality of the included studies was also assessed using the Critical Appraisal Skills Programme tool. The PRISMA framework was used for reporting the results. The electronic databases Medline, PsychINFO, CINAHL, and PubMed were searched for relevant articles. A total of three papers meeting the inclusion criteria were included in this review and two main themes identified: (1) support (which included sub-themes; social isolation and the impact on support; support from family and friends; wider support networks); (2) Emotional impact of bereavement during a pandemic. Access to support networks is crucial for CYP to understand and process their emotions relating to their bereavement experience. The pandemic meant that many usual support networks such as family and friends were inaccessible to CYP, who struggled to deal with their experience of grief during this time. Schools are a valuable support mechanism and can help CYP understand their emotions through open discussions about their bereavement. The limited empirical evidence currently available in this area of research demonstrates an important need to further understanding of the long-term impacts of dealing with pandemic-related loss in childhood.

Problem: Models of care for women with gestational diabetes mellitus (GDM) have evolved in an ad hoc way and do not meet women's needs., Background: GDM affects 50,000 Australian women per annum with prevalence quadrupling in the last ten years. Many health services are struggling to provide a quality service. People with diabetes are calling for care that focuses on their wellbeing more broadly., Aim: To examine the holistic (emotional, social, economic, and spiritual) care needs of women with GDM., Methods: Qualitative and mixed-methods studies capturing the healthcare experiences of women with GDM were searched for in CINAHL, Medline, Web of Science and Scopus. English-language studies published between 2011 and 2023 were included. Quality of studies was assessed using Crowe Critical Appraisal Tool and NVIVO was used to identify key themes and synthesise data., Findings: Twenty-eight studies were included, representing the experiences of 958 women. Five themes reflect women's holistic needs through their journey from initial diagnosis to postpartum: psychological impact, information and education, making change for better health, support, and care transition., Discussion: The biomedical, fetal-centric model of care neglects the woman's holistic wellbeing resulting in high levels of unmet need. Discontinuity between tertiary and primary services results in a missed opportunity to assist women to make longer term changes that would benefit themselves (and their families) into the future., Conclusions: The provision of holistic models of care for this cohort is pivotal to improving clinical outcomes and the experiences of women with GDM., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The goal of this study is to assess the feasibility of airway geometry as a biomarker for autism spectrum disorder (ASD). Chest computed tomography images of children with a documented diagnosis of ASD as well as healthy controls were identified retrospectively. Fifty-four scans were obtained for analysis, including 31 ASD cases and 23 controls. A feature selection and classification procedure using principal component analysis and support vector machine achieved a peak cross validation accuracy of nearly 89% using a feature set of eight airway branching angles. Sensitivity was 94%, but specificity was only 78%. The results suggest a measurable difference in airway branching angles between children with ASD and the control population., (© 2023 American Association for Anatomy.)

Objectives: To examine the relationship between preventive dental visits (PDVs) and medical expenditures while mitigating bias from unobserved confounding factors., Study Design: Retrospective data analysis of Indiana Medicaid enrollment and claims data (2015-2018) and the Area Health Resources Files., Methods: An instrumental variable (IV) approach was used to estimate the relationship between PDVs and medical and pharmacy expenditures among Medicaid enrollees. The instrument was defined as the number of adult enrollees with at least 1 nonpreventive dental claim per total Medicaid enrollees within a Census tract per year., Results: In naive analyses, enrollees had on average greater medical expenditures if they had a prior-year PDV (β = $397.21; 95% CI, $184.23-$610.18) and a PDV in the same year as expenditures were measured (β = $344.81; 95% CI, $193.06-$496.56). No significant differences in pharmacy expenditures were observed in naive analyses. Using the IV approach, point estimates of overall medical expenditures for the marginal enrollee who had a prior-year PDV (β = $325.17; 95% CI, -$708.03 to $1358.37) or same-year PDV (β = $170.31; 95% CI, -$598.89 to $939.52) were similar to naive results, although not significant. Our IV approach indicated that PDV was not endogenous in some specifications., Conclusions: This is the first study to present estimates with causal inference from a quasi-experimental study of the effect of PDVs on overall medical expenditures. We observed that prior- or same-year PDVs were not related to overall medical or pharmacy expenditures.

Skin tears, defined as traumatic wounds caused by mechanical forces, can be debilitating for individuals, causing pain and reduced mobility. Although skin tears can develop throughout the lifespan, older age can make the skin increasingly susceptible to this type of injury. Studies have found wide variation in the incidence and prevalence of skin tears, in part because of suboptimal recognition and reporting practices among healthcare professionals. Effective prevention of skin tears requires a standardised approach to risk assessment, prevention, recognition and classification, such as that offered by the International Skin Tear Advisory Panel (ISTAP) best practice recommendations. This article examines the literature on the incidence, prevalence, prevention and recognition of skin tears, and outlines some of the ISTAP best practice recommendations on risk assessment, prevention and recognition. The authors also consider the need for patient and healthcare professional education to optimise the prevention of skin tears., Competing Interests: None declared, (© 2023 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Symmetry-protected topological crystalline insulators (TCIs) have primarily been characterized by their gapless boundary states. However, in time-reversal- ([Formula: see text]-) invariant (helical) 3D TCIs-termed higher-order TCIs (HOTIs)-the boundary signatures can manifest as a sample-dependent network of 1D hinge states. We here introduce nested spin-resolved Wilson loops and layer constructions as tools to characterize the intrinsic bulk topological properties of spinful 3D insulators. We discover that helical HOTIs realize one of three spin-resolved phases with distinct responses that are quantitatively robust to large deformations of the bulk spin-orbital texture: 3D quantum spin Hall insulators (QSHIs), "spin-Weyl" semimetals, and [Formula: see text]-doubled axion insulator (T-DAXI) states with nontrivial partial axion angles indicative of a 3D spin-magnetoelectric bulk response and half-quantized 2D TI surface states originating from a partial parity anomaly. Using ab-initio calculations, we demonstrate that β-MoTe 2 realizes a spin-Weyl state and that α-BiBr hosts both 3D QSHI and T-DAXI regimes., (© 2024. The Author(s).)

Rationale/purpose: 1.Mass gathering events have resumed with the availability of SARS-CoV-2 vaccines. However, the pandemic is ongoing and such events potentially contribute to upsurges in COVID-19 cases. There is mounting evidence that public health mitigation strategies such as mask requirements, capacity restrictions, and physical distancing reduce transmission risk. However, evidence suggests imperfect compliance with these strategies. This study aimed to quantify spectators' masking behaviors and identify correlates of mask-wearing during a major sporting event., Design/methodology/approach: 2.This study used a repeated cross-sectional design, in which trained observers used a web-based application to record counts of mask-wearing., Findings: 3.Overall, 74% of spectators observed correctly wore masks. Mask-wearing behavior was associated with presumed sex, location of the spectator, game competitiveness, and whether the teams playing originated from a state with an active mask mandate., Implications: 4.Understanding the factors associated with masking behavior may help venues prepare for future events and identify innovative and targeted strategies to promote compliance with public health mitigation measures., Contribution: 5.This study makes contributions to understanding how to manage public health risks during a high-profile sporting event, specifically by identifying spectator-, game-, venue-, and state-level factors associated with mask-wearing.

Objective: We sought to measure the association of dental provider density and receipt of dental care among Medicaid-enrolled adults., Methods: We used four years of Indiana Medicaid claims and enrollment data (2015 to 2018) and the Area Health Resources File to examine the relationship between any dental visit (ADV) or any preventive dental visit (PDV) and three county-level measures of dental provider density (the total number of Medicaid-participating dentists, a binary indicator of a federally qualified health center (FQHC) with a Medicaid-participating dentist, and the overall county dentist-to-population ratio)., Results: The likelihood of ADV or PDV increased with greater density of Medicaid-participating dentists as well as dentists accepting Medicaid working at an FQHC within the county. The overall dentist-to-population ratio was not associated with dental care use among the adult Medicaid population., Conclusion: Dentist participation in Medicaid program may be a modifiable barrier to Medicaid-enrolled adults' receipt of dental care.

Importance: There is a paucity of systematically captured data on the costs incurred by society-individuals, families, and communities-from untreated mental illnesses in the US. However, these data are necessary for decision-making on actions and allocation of societal resources and should be considered by policymakers, clinicians, and employers., Objective: To estimate the economic burden associated with untreated mental illness at the societal level., Design, Setting, and Participants: This cross-sectional study used multiple data sources to tabulate the annual cost of untreated mental illness among residents (≥5 years old) in Indiana in 2019: the US National Survey on Drug Use and Health, the National Survey of Children's Health, Indiana government sources, and Indiana Medicaid enrollment and claims data. Data analyses were conducted from January to May 2022., Main Outcomes and Measures: Direct nonhealth care costs (eg, criminal justice system, homeless shelters), indirect costs (unemployment, workplace productivity losses due to absenteeism and presenteeism, all-cause mortality, suicide, caregiver direct health care, caregiver productivity losses, and missed primary education), and direct health care costs (disease-related health care expenditures)., Results: The study population consisted of 6 179 105 individuals (median [SD] age, 38.0 [0.2] years; 3 132 806 [50.7%] were women) of whom an estimated 429 407 (95% CI, 349 526-528 171) had untreated mental illness in 2019. The economic burden of untreated mental illness in Indiana was estimated to be $4.2 billion annually (range of uncertainty [RoU], $2.1 billion-$7.0 billion). The cost of untreated mental illness included $3.3 billion (RoU, $1.7 billion-$5.4 billion) in indirect costs, $708.5 million (RoU, $335 million-$1.2 billion) in direct health care costs, and $185.4 million (RoU, $29.9 million-$471.5 million) in nonhealth care costs., Conclusion and Relevance: This cross-sectional study found that untreated mental illness may have significant financial consequences for society. These findings put into perspective the case for action and should be considered by policymakers, clinicians, and employers when allocating societal resources and funding. States can replicate this comprehensive framework as they prioritize key areas for action regarding mental health services and treatments.

Socioeconomic factors such as poor health and poor nutrition in low- and middle-income countries (LMICs) may favour inflammatory reactions, thus contributing to the recurrence of rheumatic fever (RF) and thereby modifying trends in rheumatic heart disease (RHD). Apart from epidemiological studies, studies of HIV infections in RHD patients are limited. This systematic review synthesises data on the prevalence and impact of HIV infections or AIDS on RHD from PubMed, Scopus, Web of Science databases up to April 2021. The outcomes were managed using PRISMA guidelines. Of a total of 15 studies found, 10 were eligible for meta-analyses. Meta-analysis found that 17% (95 % CI 8-33, I 2 = 91%) of adults in cardiovascular disease (CVD) cohorts in Southern Africa are HIV positive. The proportion of RHD diagnosed among people living with HIV was 4% (95% CI 2-8, I 2 = 79%) for adults but lower [2% (95% CI 1-4, I 2 = 87%)] among perinatally infected children. Despite limited reporting, HIV-infected patients with RHD are prone to other infections that may enhance cardiac complications due to poor immunological control. PROSPERO registration number: CRD42021237046., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)

Competing Interests: The author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request.

The pathogenesis of coronavirus disease 2019 (COVID-19) pneumonia remains poorly understood. The urine proteome of hospitalized patients with severe COVID-19 pneumonia, compared with severe non-COVID-19 pneumonia controls, was distinct and associated with lower abundance of several host proteins. Protein-specific machine learning analysis outlined biomarker combinations able to differentiate COVID-19 pneumonia from non-COVID-19 pneumonia controls., Competing Interests: Potential conflicts conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Understanding factors associated with risk of pain allows residents and clinicians to plan care and set priorities, however, factors associated with pain in nursing home residents has not been conclusively studied., Aim: To evaluate the association between pain and nursing home (NH) resident demographic and clinical characteristics., Design: Retrospective analysis of Minimum Data Set 3.0 records of nursing home residents residing in 44 Indiana NHs between September 27, 2011 and December 27, 2019 (N = 9,060)., Results: Pain prevalence in this sample of NH residents was 23.7%. Of those with pain, 28.0% experienced moderate to severe/frequent pain and 54.6% experienced persistent pain. Risk factors for moderate to severe/frequent pain include female sex; living in a rural setting; intact, mildly, or moderately impaired cognition; arthritis; contracture; anxiety; and depression. In contrast, stroke and Alzheimer's disease and Alzheimer's-disease related dementias (AD/ADRD) were associated with decreased risk of reporting moderate to severe/frequent pain, likely representing both the under-assessment and under-reporting of pain among cognitively impaired NH residents. Risk factors for persistent pain included age <70, Black race, living in a rural location, intact cognition, contracture, and depression., Conclusions: Pain remains a pressing problem for NH residents. In this study, we identified demographic and clinical factors associated with moderate to severe frequent pain and persistent pain. Residents with a diagnosis of AD/ADRD were less likely to report pain, likely representing the difficulty of evaluating pain in these residents. It is important to note that those with cognitive impairment may not experience any less pain, but assessment and reporting difficulties may make them appear to have less pain. Knowledge of factors associated with pain for NH residents has the potential for improving the ability to predict, prevent, and provide better pain care in NH residents., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Disclosures/conflicts of interest: Connie S. Cole: no conflicts of interest Janet S. Carpenter: University of Wisconsin Milwaukee, relationship now ended; Simumetrix, relationship now ended; Mapi Research Trust, relationship ongoing. Justin Blackburn: no conflicts of interest Chen X. Chen: no conflicts of interest Susan E. Hickman: no conflicts of interest, (Copyright © 2023 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Background: Spinal anaesthesia, the most common form of anaesthesia for caesarean section, leads to sympathetic blockade and profound maternal hypotension resulting in adverse maternal and neonatal outcomes. Hypotension, nausea and vomiting remain common but until the publication of the National Institute of Health and Care Excellence (NICE) 2021 guidance, no national guideline existed on how best to manage maternal hypotension following spinal anaesthesia for caesarean section. A 2017 international consensus statement recommended prophylactic vasopressor administration to maintain a systolic blood pressure of >90% of an accurate pre-spinal value, and to avoid a drop to <80% of this value. This survey aimed to assess regional adherence to these recommendations, the presence of local guidelines for management of hypotension during caesarean section under spinal anaesthesia, and the individual clinician's treatment thresholds for maternal hypotension and tachycardia., Methods: The West Midlands Trainee-led Research in Anaesthesia and Intensive Care Network co-ordinated surveys of obstetric anaesthetic departments and consultant obstetric anaesthetists across 11 National Health Service Trusts in the Midlands, England., Results: One-hundred-and-two consultant obstetric anaesthetists returned the survey and 73% of sites had a policy for vasopressor use; 91% used phenylephrine as the first-line drug but a wide range of recommended delivery methods was noted and target blood pressure was only listed in 50% of policies. Significant variation existed in both vasopressor delivery methods and target blood pressures., Conclusions: Although NICE has since recommended prophylactic phenylephrine infusion and a target blood pressure, the previous international consensus statement was not adhered to routinely., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Dystonia is common, debilitating, often medically refractory, and difficult to diagnose. The gold standard for both clinical and mouse model dystonia evaluation is subjective assessment, ideally by expert consensus. However, this subjectivity makes translational quantification of clinically-relevant dystonia metrics across species nearly impossible. Many mouse models of genetic dystonias display abnormal striatal cholinergic interneuron excitation, but few display subjectively dystonic features. Therefore, whether striatal cholinergic interneuron pathology causes dystonia remains unknown. To address these critical limitations, we first demonstrate that objectively quantifiable leg adduction variability correlates with leg dystonia severity in people. We then show that chemogenetic excitation of striatal cholinergic interneurons in mice causes comparable leg adduction variability in mice. This clinically-relevant dystonic behavior in mice does not occur with acute excitation, but rather develops after 14 days of ongoing striatal cholinergic interneuron excitation. This requirement for prolonged excitation recapitulates the clinically observed phenomena of a delay between an inciting brain injury and subsequent dystonia manifestation and demonstrates a causative link between chronic striatal cholinergic interneuron excitation and clinically-relevant dystonic behavior in mice. Therefore, these results support targeting striatal ChIs for dystonia drug development and suggests early treatment in the window following injury but prior to dystonia onset., One Sentence Summary: Chronic excitation of dorsal striatal cholinergic interneuron causes clinically-relevant dystonic phenotypes in mice.

Purpose: To examine the longitudinal relationship between the age or shelf-life of common type 2 diabetes laboratory tests for serum creatinine, cholesterol, and glycated hemoglobin A1c conducted in outpatient settings and subsequent inpatient hospitalizations and emergency department visits., Methods: This study analyzes panel data from two healthcare delivery systems' electronic health records (EHR) for patients aged 18 years and older managing type 2 diabetes. We used EHR data to quantify the age of three laboratory tests: serum creatinine, cholesterol, and glycated hemoglobin A1c. Encounter data were used to determine the frequency of inpatient hospitalizations and emergency department visits. Negative binomial regressions with fixed effects were performed to compute marginal effects, levels of statistical significance, and 95% confidence intervals., Results: The average age for serum creatinine laboratory tests was 1.51 months (95%CI: 1.49-1.53). We computed older average ages for hemoglobin A1c (mean:6.17 months; 95%CI: 6.11-6.23) and serum creatinine tests (mean: 8.73; 95%CI: 8.65-8.81). Older laboratory tests were associated with an increase in the total expected counts of subsequent inpatient hospitalizations (ME = 0.047; p < 0.001) and ED visits (ME = 0.034; p < 0.001)., Conclusion: Findings from this study indicate that older type 2 diabetes laboratory tests are associated with increases in the total expected count of subsequent inpatient hospitalizations and emergency department visits. Future research should examine the actionability of laboratory test values to determine associations with healthcare outcomes., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01250-0., Competing Interests: Competing InterestsThe authors of this study have no relevant financial or non-financial interests to disclose., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background and Objectives: More than nine million U.S. adults have a co-occurring mental health and substance use disorder. The self-medication hypothesis suggests that individuals with unmet need may alleviate the symptoms of their mental illness by using alcohol or drugs. We examine the relationship between unmet mental health need and subsequent substance use among individuals with a history of depression as well as differences in metro and nonmetro areas., Methods: We used repeated cross-sectional data from the National Survey on Drug Use and Health (NSDUH), 2015-2018 after identifying individuals with depression in the past year (n = 12,211). We used logistic regressions with interaction terms to examine the association between unmet need for mental health care and substance use by geographic location., Results: Unmet mental health need was associated with increased use of marijuana (odds ratio [OR] = 1.32, 95% confidence interval [CI]: 1.08-1.64), illicit drugs (OR = 1.75, 95% CI: 1.19-2.58), and prescription drugs (OR = 1.89, 95% CI: 1.19-3.00) among individuals with depression, which did not vary by geographic location. Unmet need was not associated with increased heavy alcohol drinking (OR = 0.87, 95% CI: 0.60-1.26)., Discussion and Conclusions: No differences in substance usage between metro and nonmetro populations were observed for those with an unmet need for mental health care. We found support for the self-medication hypothesis among individuals with depression with respect to alcohol., Scientific Significance: We examine whether individuals with depression and unmet care needs are more likely to self-medicate with substances including prescription drugs. Due to higher unmeet needs in nonmetro areas, we examine whether the likelihood of self-medication differs in metro and nonmetro areas., (© 2023 The Authors. The American Journal on Addictions published by Wiley Periodicals LLC on behalf of The American Academy of Addiction Psychiatry (AAAP).)

Our aim was to utilise a 241-gene RNA hybridisation capture sequencing (CaptureSeq) gene panel to identify unexpected fusions in undifferentiated, unclassified or partly classified sarcomas of young individuals (<40 years). The purpose was to determine the utility and yield of a large, targeted fusion panel as a tool for classifying tumours that do not fit typical diagnostic entities at the time of the original diagnosis. RNA hybridisation capture sequencing was performed on 21 archival resection specimens. Successful sequencing was obtained in 12 of 21 samples (57%), two of which (16.6%) harboured translocations. A novel NEAT1::GLI1 fusion, not previously reported in the literature, presented in a young patient with a tumour in the retroperitoneum, which displayed low grade epithelioid cells. The second case, a localised lung metastasis in a young male, demonstrated a EWSR1::NFATC2 translocation. No targeted fusions were identified in the remaining 83.4% (n=10) of cases. Forty-three per cent of the samples failed sequencing as a result of RNA degradation. RNA-based sequencing is an important tool, which helps to redefine the classification of unclassified or partly classified sarcomas of young adults by identifying pathogenic gene fusions in up to 16.6% of the cases. Unfortunately, 43% of the samples underwent significant RNA degradation, falling below the sequencing threshold. As CaptureSeq is not yet available in routine pathology practice, increasing awareness of the yield, failure rate and possible aetiological factors for RNA degradation is fundamental to maximise laboratory procedures to improve RNA integrity, allowing the potential identification of significant gene alterations in solid tumours., (Copyright © 2023 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Electrochemistry education of future researchers and citizens is crucial if we are to decarbonise economies and reach targets for net zero. In this paper, we take an overview of electrochemistry within school education. We used curriculum documents obtained from national and state education department websites and from local teachers, examples of assessments and insights from the chemistry education literature to evaluate the extent of electrochemistry education around the world. We found that there is a great deal of electrochemistry included in the intended curriculum for high schools although there is variability depending on how early students are able to specialise in a smaller number of subjects. A range of contexts are used to illustrate the key ideas including galvanic and electrolytic cells, electrolysis and analysis. There is generally constructive alignment between assessment items and the intended curriculum although in some cases assessment was more simplistic than the intended curriculum would suggest. The effectiveness of the taught curriculum is undermined by low teacher confidence in teaching electrochemistry especially more advanced concepts. Additionally, there are a number of misconceptions generated when students learn electrochemistry with some of these potentially arising from published resources such as textbooks., Supplementary Information: The online version contains supplementary material available at 10.1007/s10008-023-05548-0., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Sex determination is the process whereby the bipotential embryonic gonads become committed to differentiate into testes or ovaries. In genetic sex determination (GSD), the sex determining trigger is encoded by a gene on the sex chromosomes, which activates a network of downstream genes; in mammals these include SOX9, AMH and DMRT1 in the male pathway, and FOXL2 in the female pathway. Although mammalian and avian GSD systems have been well studied, few data are available for reptilian GSD systems., Results: We conducted an unbiased transcriptome-wide analysis of gonad development throughout differentiation in central bearded dragon (Pogona vitticeps) embryos with GSD. We found that sex differentiation of transcriptomic profiles occurs at a very early stage, before the gonad consolidates as a body distinct from the gonad-kidney complex. The male pathway genes dmrt1 and amh and the female pathway gene foxl2 play a key role in early sex differentiation in P. vitticeps, but the central player of the mammalian male trajectory, sox9, is not differentially expressed in P. vitticeps at the bipotential stage. The most striking difference from GSD systems of other amniotes is the high expression of the male pathway genes amh and sox9 in female gonads during development. We propose that a default male trajectory progresses if not repressed by a W-linked dominant gene that tips the balance of gene expression towards the female trajectory. Further, weighted gene expression correlation network analysis revealed novel candidates for male and female sex differentiation., Conclusion: Our data reveal that interpretation of putative mechanisms of GSD in reptiles cannot solely depend on lessons drawn from mammals., (© 2023. The Author(s).)

Background: The AquaCHROM™ ECC method from CHROMagar is intended for the detection and enumeration of Escherichia coli and coliform bacteria in 100 mL water samples after 18-24 h of incubation at 35-37°C., Objective: To validate the AquaCHROM ECC method for qualitative and quantitative detection of E. coli and coliforms with different water matrixes., Methods: Inclusivity/exclusivity studies were conducted. AquaCHROM ECC was compared to U.S. cultural reference methods in unpaired matrix studies for detection of E. coli and coliforms in tap water, well water, lake water, and bottled water, and for enumeration in tap water, well water, and lake water. Three production lots of AquaCHROM ECC were tested for product consistency and stability. Variations in incubation time and temperature were evaluated in robustness testing., Results: Inclusivity/exclusivity results demonstrated expected performance with the exception of three strains of Salmonella enterica, two species of Shigella, and one strain of Aeromonas, which turned the media blue or yellow. Results from the matrix studies demonstrated that AquaCHROM ECC and the reference methods are not statistically different for detection of E. coli and coliforms and statistically equivalent for enumeration of E. coli and coliforms. The AquaCHROM ECC powder production was proven to be consistent with a 24-month shelf life. Variation in temperature did not affect the method performance. Shortening the incubation time is not recommended., Conclusion: AquaCHROM ECC is an effective method for the detection and enumeration of E. coli and coliforms for the water matrixes evaluated., Highlights: The AquaCHROM ECC method is a quick, one-step method for the recovery and enumeration of E. coli and coliforms in 100 mL water samples. It is a non-agar-based chromogenic medium which provides a clear result without the use of a UV lamp., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Frequent testing for Legionella concentration in water is required by most health risk monitoring organizations worldwide. Domestic hot water and cooling tower water networks must be regularly controlled to prevent Legionnaires' disease, a potentially deadly lung infection. MICA Legionella is the fastest culture-based detection method for all serogroups of Legionella pneumophila, with automatic enumeration in 48 h and no need for confirmation., Objective: This study compares the performance and robustness of MICA Legionella with the reference method ISO 11731:2017 for the enumeration of culturable L. pneumophila., Methods: MICA Legionella and ISO 11731:2017 results were compared for domestic hot water and cooling tower water. Inclusivity and exclusivity were tested on reference and environmental strains. Ruggedness, lot-to-lot consistency, and stability of the reagents kit were also studied., Results: Enumeration of L. pneumophila by MICA Legionella was statistically equivalent to ISO 11731:2017 in both matrixes. In cooling tower waters, MICA Legionella showed better sensitivity than ISO 11731:2017. It presented a 94% sensitivity and a 97% specificity., Conclusion: MICA Legionella is a highly sensitive and specific method for culturable L. pneumophila enumeration. It presents, in 48 hours, equivalent or better results than ISO 11731:2017. Its protocol is robust to variations. Its reagents kit is stable for up to 18 months., Highlights: MICA Legionella is a robust and reliable method for the enumeration of culturable L. pneumophila in domestic and cooling tower water. It reduces significantly the number of sample pretreatments required in ISO 11731:2017. Automatic identification and enumeration of L. pneumophila microcolonies eliminates the requirement to have skilled analysts and limits the results variability. It also greatly reduces the time to results to 48 h instead of 7-10 days with ISO 11731:2017 while providing statistically equivalent results., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL.)

Purpose: The number of patients tapered from long-term opioid therapy (LTOT) has increased in recent years in the United States. Some patients tapered from LTOT report improved quality of life, while others face increased risks of opioid-related hospital use. Research has not yet established how the risk of opioid-related hospital use changes across LTOT dose and subsequent tapering. Our objective was to examine associations between recent tapering from LTOT with odds of opioid-related hospital use., Methods: Case-crossover design using 2014-2018 health information exchange data from Indiana. We defined opioid-related hospital use as hospitalizations, and emergency department (ED) visits for a drug overdose, opioid abuse, and dependence. We defined tapering as a 15% or greater dose reduction following at least 3 months of continuous opioid therapy of 50 morphine milligram equivalents (MME)/day or more. We used conditional logistic regression to estimate odds ratios (OR) with 95% confidence intervals (CI)., Results: Recent tapering from LTOT was associated with increased odds of opioid-related hospital use (OR: 1.50, 95%CI: 1.34-1.63), ED visit (OR: 1.52; 95%CI: 1.35-1.72), and inpatient hospitalization (OR: 1.40; 95%CI: 1.20-1.65). We found no evidence of heterogeneity of the effect of tapering on opioid-related hospital use by gender, age, and race. Recent tapering among patients on a high baseline dose (>300 MME) was associated with increased odds of opioid-related hospital use (OR: 2.95, 95% CI: 2.12-4.11, p < 0.001) compared to patients on a lower baseline doses., Conclusions: Recent tapering from LTOT is associated with increased odds of opioid-related hospital use., (© 2022 John Wiley & Sons Ltd.)

Intragenic CpG dinucleotides are tightly conserved in evolution yet are also vulnerable to methylation-dependent mutation, raising the question as to why these functionally critical sites have not been deselected by more stable coding sequences. We previously showed in cell lines that altered exonic CpG methylation can modify promoter start sites, and hence protein isoform expression, for the human TP53 tumor suppressor gene. Here we extend this work to the in vivo setting by testing whether synonymous germline modifications of exonic CpG sites affect murine development, fertility, longevity, or cancer incidence. We substituted the DNA-binding exons 5-8 of Trp53, the mouse ortholog of human TP53, with variant-CpG (either CpG-depleted or -enriched) sequences predicted to encode the normal p53 amino acid sequence; a control construct was also created in which all non-CpG sites were synonymously substituted. Homozygous Trp53-null mice were the only genotype to develop tumors. Mice with variant-CpG Trp53 sequences remained tumor-free, but were uniquely prone to dental anomalies causing jaw malocclusion (p < .0001). Since the latter phenotype also characterises murine Rett syndrome due to dysfunction of the trans-repressive MeCP2 methyl-CpG-binding protein, we hypothesise that CpG sites may exert non-coding phenotypic effects via pre-translational cis-interactions of 5-methylcytosine with methyl-binding proteins which regulate mRNA transcript initiation, expression or splicing, although direct effects on mRNA structure or translation are also possible., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Epstein et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Domestic violence (DV) shelters are an essential service for survivors and their children. While research has demonstrated global increases in DV during COVID-19, little is known about the experiences of DV shelter staff. This study aimed to understand DV shelter staff's experiences and how they navigated the early stages of the pandemic., Methods: Researchers disseminated a cross-sectional online survey, first to state DV coalitions and then directly to DV shelters. Univariate and bivariate analyses were used for multiple-choice items, and patterns were identified using thematic analysis for open-ended responses., Results: Survey participants included 368 DV staff (180 leadership, 167 direct services, and 21 other roles) from 48 states. They reported little change to their schedules and mixed feelings of shelter preparedness for the pandemic. Participants described shelter methods for preventing the spread of COVID-19, changes in shelter policies and satisfaction with such policies, and the impacts of the pandemic on themselves and survivors. Balancing survivor autonomy with the health and safety of staff and other residents proved to be one of the most consistently challenging tasks. Participants also described how programs adapted to changing regulations and continued to serve survivors throughout this challenging time., Conclusion: Several innovative practices were implemented by staff throughout the pandemic, including expansions in technology use and non-residential services. Most reported feeling prepared for a similar crisis in the future. We offer five recommendations for DV shelters and their funders, including increased mental health support for staff and greater transparency in policies for both shelter residents and staff., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Understanding changes in nursing home (NH) resident pain over time would provide a more informed perspective, allowing opportunities to alter the course of illness, plan care, and set priorities. Therefore, the purpose of this analysis was to identify and characterize clinically meaningful, dynamic pain trajectories in NH residents., Methods: Retrospective longitudinal analysis of NH resident pain scores with a length of stay >100 days (N = 4864). Group-based trajectory modeling was applied to Minimum Data Set 3.0 assessments to identify pain trajectories. Trajectories were then characterized using unadjusted and adjusted cross-sectional associations between residents' demographic and clinical characteristics and their pain trajectory., Results: We identified four distinct trajectories: (1) consistent pain absence (48.9%), (2) decreasing-increasing pain presence (21.8%), (3) increasing-decreasing pain presence (15.3%), and (4) persistent pain presence (14.0%). Demographics of younger age and living in a rural area were associated with the persistent pain presence trajectory. Clinical variables of obesity and intact cognition were associated with being in the persistent pain presence trajectory. A smaller proportion of residents with moderately or severely impaired cognition were in any of the trajectory groups with pain., Conclusions: We identified and characterized four pain trajectories among NH residents, including persistent pain presence which was associated with demographic characteristics (younger, female, rural) and clinical factors (obese, fracture, contracture). Moreover, residents with a diagnosis of Alzheimer's disease or dementia were less likely to be in any of the three trajectories with pain, likely representing the difficulty in evaluating pain in these residents. It is important that NH staff understand, recognize, and respond to the factors associated with the identified pain trajectories to improve mitigation of potentially persistent pain (e.g., hip fracture, contracture) or improve proxy pain assessment skills for residents at risk for under reporting of pain (e.g., Alzheimer's Disease)., (© 2022 The American Geriatrics Society.)

Avoidable hospitalizations among nursing home residents result in poorer health outcomes and excess costs. Consequently, efforts to reduce avoidable hospitalizations have been a priority over the recent decade. However, many potential interventions are time-intensive and require dedicated clinical staff, although nursing homes are chronically understaffed. The OPTIMISTIC project was one of seven programs selected by CMS as "enhanced care & coordination providers" and was implemented from 2012 to 2020. This qualitative study explores the perceptions of the nurses that piloted a virtual care support project developed to expand the program's reach through telehealth, and specifically considered how nurses perceived the effectiveness of this program. Relationships, communication, and access to information were identified as common themes facilitating or impeding the perceived effectiveness of the implementation of virtual care support programs within nursing homes., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Kathleen Unroe serves as the CMO of Probari, Inc, a program to train nurses to reduce nursing home hospital transfers. There are no other potential conflicts of interest to report., (© The Author(s) 2023.)

Background: The 3M™ Petrifilm™ Rapid Yeast and Mold Count (RYM) Plate contains nutrients supplemented with antibiotics, a cold-water-soluble gelling agent, and an indicator system that facilitates yeast and mold enumeration in 48-60 h., Objective: The objective of this study is to evaluate the 3M Petrifilm RYM Plate in a matrix extension study for the enumeration of yeast and mold on stainless steel, sealed concrete, and rubber surfaces., Methods: The 3M Petrifilm RYM Plate was compared to the U.S. Food and Drug Administration Bacteriological Analytical Manual, Ch. 18: Yeasts, Molds and Mycotoxins in a paired matrix study for enumeration of yeast and mold on stainless steel, sealed concrete, and rubber environmental surfaces., Results: The 3M Petrifilm RYM Plate demonstrated equivalent performance to the reference method for enumeration of yeast and mold from stainless steel, sealed concrete, and rubber environmental surfaces. There were no significant statistical differences between the 3M Petrifilm RYM Plate and reference method results for the three matrixes evaluated., Conclusion: The 3M Petrifilm RYM Plate is an effective plating method for enumerating yeast and mold when analyzing stainless steel, sealed concrete, and rubber surfaces., Highlights: The 3M Petrifilm RYM Plate method allows the user to obtain accurate results within 48-60 h in the matrices evaluated for the presence of yeast and mold when incubated at 25 ± 1°C or 28 ± 1°C. Interpretation and colony counting was straightforward and the 3M Petrifilm RYM Plate method required no additional agar or Petri dishes, creating an easier workflow by cutting down on supplies, sample plating time, and most noticeably, occupying less space in the incubator., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL.)