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Black girls in the United States are disproportionately diagnosed with sexually transmitted infections (STIs), which can increase the risk of contracting HIV (human immunodeficiency virus), compared to adolescent girls of other races. Therefore, this study was designed to understand barriers to impactful HIV/STI and substance use prevention programmes for Black girls. Data was collected between October 2021 and June 2022 from twelve focus groups which included (N = 62) participants who identified as Black and female between the ages of 13 and 18 years old. Using intersectionality theory as a guiding framework, the data were analysed thematically. The analysis revealed three themes: 1) need for parent-child discussions on sex; 2) stigma in schools; 3) suggestions for Black girl-centred prevention programming. Participants described minimal discussion about sex in their household as well as STI/HIV and substance abuse stigma as barriers to impactful sex education. They also indicated that current substance use and STI/HIV prevention interventions are not tailored to the experience of Black girls and offered suggestions for improvement. In sum, participants pointed out several barriers to existing sex education and substance abuse prevention programs. Findings revealed that HIV and drug use prevention information and knowledge may be best received from older peers in small private settings that can allow for intimate discussion and sharing of reliable information on HIV education, aetiology, and safer sexual practices. In addition, the study findings support the need to develop a racial and gender-specific prevention programming that fosters peer relationships, social support, and empowerment-based principles.

Abstract Background Self-Directed Learning (SDL) is a theory of andragogy in which adult learners take their own initiative to identify and tailor their individual learning process and outcomes. In undergraduate medical education, SDL aims to develop medical students into lifelong learners. This study aims to estimate the overall effectiveness of self-directed learning compared to traditional didactic learning (TDL). Methods We performed a systematic review and meta-analysis according to the PRISMA statement. A systematic search was used across PubMed, Scopus, Embase and Google Scholar to identify peer-reviewed articles spanning from January 1, 2014, to May 30, 2024. Key words used were “self-directed learning” AND “undergraduate medical education.” Forest plots were generated with the Open Meta-analyst Software, comparing SDL and TDL. Results A total of 2,955 titles and abstracts were screened for eligibility, of which 95 articles met the eligibility criteria for full-text review. Following a more detailed screening, 19 articles met the criteria for inclusion in the systematic review and 14 articles met the criteria for inclusion in the meta-analysis. The systematic review included 2,098 students while the meta-analysis included 1,792 students. The overall mean difference for all studies was 2.399, 95% CI [0.121–4.678], and I2 = 98.56%. Conclusion Self-directed learning compared to traditional didactic learning is an effective learning strategy in medical undergraduate education and has the potential to aid in students’ learning and improve their cognitive performance. Moreover, SDL nurtures qualities such as autonomy, curiosity, and self-regulation, which are essential for success in the ever-evolving field of medicine.

Abstract Adherence to antiretroviral therapy (ART) is essential for the effective management of HIV, which includes keeping the HIV viral load undetectable. This study aimed to determine whether certain ART medications are more “forgiving” of poor adherence in achieving viral suppression. We identified subgroups of ART medication usage and determined the extent to which ART adherence is associated with viral suppression across those subgroups. Data came from claims and clinical records (2017–2019) of 3,552 HIV-positive adult members of a Medicaid managed care plan. Pharmacy fill data were examined to characterize ART medications using latent class analysis (LCA), which captures the complexity of real-world ART usage (i.e., multiple medications, ART switching). LCA yielded five ART medication patterns over three years, mostly characterized by recent medications and formulations of ART, though they varied in number of tablets and in medication class. Mixed effects logistic regression models were estimated to determine whether odds of viral suppression differed by ART adherence level. After adjusting for covariates, those with at least 90% adherence (i.e., 90 to

Background: Erythrodermic psoriasis (EP) is a potentially life-threatening disease, and there is currently no consensus regarding its optimal treatment. Biological drugs approved for Psoriasis Vulgaris treatment have been used as alternatives to traditional medications. Objective: To evaluate the clinical response and tolerability of anti- interleukin 17 (IL17) biologic drugs during a 2-year-follow-up. Methods: This was a retrospective prospective study. EP cases, defined as >75% body surface area involvement, in patients ≥18 years old treated with anti-IL17 for at least 6 consecutive months were enrolled and then followed until 104 weeks. Patient characteristics, overall clinical responses, Psoriasis Area Severity Index score changes, and adverse events were analyzed. Results: Sixteen patients met the criteria, of which 50% had achieved the Psoriasis Area Severity Index 100 response at week 12 and in 93.7% at week 24. In the prospective observation of the cohort, 87.5% were still in remission at week 52 and 81.25% at 104 weeks, without adverse events. The 3 patients in whom the treatment was interrupted lost efficacy and were switched to other therapies. Limitations: Only descriptive analysis was conducted due to the limited number of patients. Conclusions: A satisfactory long-term clinical response without adverse effects was observed in this case series, suggesting the interest of anti-IL17 in EP treatment.

Large waders including herons and egrets are important ecological wetland health indicators since these species are sensitive to a complex set of environmental factors. Anthropogenic factors are driving major changes in coastal and inland wetlands. We investigated the relationship between environmental variables, productivity, fish diversity and large waders in southwestern India. These variables cover climatic variables (rainfall), sediment variables (salinity, pH, organic carbon, nitrogen, phosphorus), water variables (Salinity, pH, temperature, nitrate, phosphate), primary productivity (Chlorophyll-a) and prey availability (mean fish stock availability). Densities of all the studied wader species decreased significantly from 2010 to 2019, with highest densities in agroecosystems or estuarine habitats and in post-monsoon seasons but lowest in mudflats and in monsoon seasons. Structural equational modelling revealed that rainfall and organic carbon positively affected the primary productivity, whereas water variables (nitrate, salinity and phosphate) positively affected the fish stock availability. This in turn positively affected the density of large wading birds. The decreasing trend of water nitrate negatively affected the primary productivity and density of waterbirds while rainfall negatively affected fish stock availability and waterbird density. Sediment phosphorous adversely affected both the biotic variables and the density of waterbirds. Sediment variables (salinity, pH, and phosphorus) increased over years, whereas organic carbon and nitrogen in the sediment decreased significantly. Salinity, water temperature, pH, and phosphate showed a significant increase while water nitrate, and chlorophyll-a decreased over the period of study. Significant decline in fish stock availability and altered environmental variables resulted in long term decline in the abundance of wading birds. Thus, large waders have adapted to these long-term, anthropogenically driven, environmental changes by shifting to agroecosystems and estuaries as their alternate foraging habitats. These population declines indicate consistent decline in ecosystem health of wetlands. Strategies need to be formulated to mitigate declines and restore ecosystem health.

Background Neurohormonal blocking drugs, like beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs), are recommended for treating anthracycline-induced left ventricular dysfunction (AILVD). However, there is limited evidence supporting their benefit. Therefore, this study evaluated associations of neurohormonal blockers and other clinical factors with recovery of left ventricular ejection fraction (LVEF) in patients with AILVD. Methods This retrospective chart review assessed patients treated with at least one dose of anthracycline, then had ≥10% LVEF reduction or post-anthracycline LVEF value

Summary: Genetic factors related to pregnancy-related traits are understudied, especially in ancestrally diverse cohorts. To assess maternal contributions to hypertensive disorders of pregnancy (HDP), we performed a multi-ancestry genome-wide association study (GWAS) of HDP in data from the North Carolina-based Personalized Environment and Genes Study (PEGS) cohort with validation in the UK Biobank (UKBB). The GWAS revealed two maternal loci associated with HDP at the genome-wide significance level. The lead independent variants were rs114954125 on chromosome 2 (near LRP1B; odds ratio [OR] [95% confidence interval {CI}]): 2.96 [2.02–4.34]; p = 2.82 × 10−8) and rs61176331 on chromosome 3 (on RARB; OR (95% CI): 3.08 (2.12–4.48); p = 3.52 × 10−9). We validated the associations near RARB with a meta-analysis of PEGS and the UKBB. We also identified cis-expression quantitative trait loci in the candidate region associated with decreased RARB expression in macrophage cells exposed to Salmonella. Chromatin mapping in FUMA identified a significant interaction within chromosome 3’s enhancer and open chromatin regions, with strong effects observed for RARB and H3P10 gene regulation in mesendoderm cells, mesenchymal stem cells, and trophoblast-like stem cells. We applied existing polygenic scores (PGS) for preeclampsia and gestational hypertension and found that the scores were significantly associated with HDP in PEGS. The findings demonstrate the power of multi-ancestry studies for genetic discovery and highlight the relationship between immune response, regulation, and HDP and the utility of PGS for risk prediction. (PEGS is registered at ClinicalTrials.gov: NCT00341237.)

AIM: To examines public perceptions, attitudes and knowledge concerning antibiotics, with a particular focus on the impact of OTC accessibility and affordability. BACKGROUND: The availability of over-the-counter (OTC) medicines including antibiotics and economic disparities encourages unsupervised self-medication which may pose a threat to increase antibiotic resistance. METHOD: This cross-sectional survey utilized random sampling, stratified by demographics, to assess adults' perceptions, attitudes and understanding of antibiotics in our region. The questionnaire, covered demographics, usage patterns, resistance knowledge, OTC availability and affordability concerns. Data were gathered through face-to-face interactions and social media. RESULT: Out of 1,024 invited participants, 719 respondents were participated in the survey. Our study reveals that 225(31.2%) of daily and monthly wage earners opt to self-medication, primarily due to the high cost of consultations with 121(16.8%) of respondents citing this as their reason. Despite 195(27.1%) being satisfied with OTC medications, common issues persist such as affordability with 263(36.5%) of daily wage earners finding antibiotics too costly. Compounding the issue, 372(51.7%) do not complete their full course of antibiotics, increasing the risk of resistance. 58.5% of respondents believed that antibiotics are used to treat viral infection such as common cold and influenza. CONCLUSION: The findings of our study indicate that daily wage earners struggle to afford medications. It's important to implement the national pharmaceutical policy more effectively. Increasing the availability and accessibility of generic drugs is essential. Additionally, policies to restrict the purchase of antibiotics without prescription and to educate on their proper use are urgently needed.

Introduction: Neonatal intubation is a lifesaving skill that a variety of clinicians need to establish as it can be required anywhere babies are born or hospitalised and cannot depend on the immediate availability of an experienced senior clinician. However, neonatal intubation is complex and risky, requiring technical and non-technical skill competence. Studies report that rates of successful neonatal intubation by junior clinicians are low, providing a mandate to examine the best methods to improve skill acquisition, retention, and transfer. Method: We utilised PRISMA-ScR methodology to capture the range of training approaches in the simulation and clinical settings, and to assess the range of technical and non-technical skill outcome measures that were used in the included studies. Databases were searched from inception to August 2024 to identify studies reporting outcomes for medical practitioners-in-training, nurses, and nurse practitioners. Identified studies meeting inclusion criteria underwent data charting with study characteristics tabulated. Results: Twenty-six studies (involving 1449 participants) were included. Training methodology was diverse and included self-directed learning, didactic education, demonstration, simulation-based training (SBT), instructor feedback, debriefing and supervised clinical practice. Most of the studies (96 %) used multiple training methods with education and SBT most frequently used. Thirteen studies reported outcomes in clinical settings, including seven that demonstrated changes in technical skills following education and SBT. Two studies that assessed transfer of skills failed to show successful transfer from simulation to a clinical setting. Two articles reported the transfer of skills between direct and video laryngoscope devices. Only one study evaluated skill retention (at 6–9 months) but did not demonstrate proficiency after initial training or at follow up. No studies described the effects of training on non-technical skills. Conclusion: No included studies or combination of studies seems likely to provide a high-certainty evidence-basis for optimal training methodology. Results suggested using a training bundle including education, SBT and supervision. Knowledge gaps remain, including the most effective methodology for non-technical skill training. In addition, the evidence of technical skill retention beyond the immediate training episode, and transfer to a variety of clinical environments is very limited. Given the importance of successful neonatal intubation, more research in these areas is justified.

Abstract Objective To understand how diabetes mellitus (DM) diagnosed at different ages of adulthood are associated with various incident subsequent non-communicable diseases (NCDs). Methods We performed a nationwide population-based analysis comparing 212 participants first diagnosed with DM at 20–39, 40–49, 50–59, or 60–69 years of age, with 17,541 participants without DM history, using data from the Indonesian Family Life Survey. Subsequent NCDs that were examined included hypertension, lung diseases, heart diseases, arthritis, liver diseases, kidney diseases, and digestive diseases. We estimated weighted risk ratios and 95% confidence intervals using Poisson regression, adjusting for age, sex, urbanicity, and tobacco use history. Results Those diagnosed with DM in all age groups had significantly higher risk of hypertension, compared with those without DM history. Compared with those without DM history, younger individuals with DM diagnosed at 20–39 years of age had significantly higher risks of lung diseases and arthritis, and those with DM diagnosed at 20–49 years of age had significantly higher risk of digestive diseases. Older individuals with DM diagnosed at 40–69 years of age had significantly higher risk of liver diseases, and those with DM diagnosed at 40–59 years of age had significantly higher risk of heart diseases, compared with those without DM history. Participants with DM were diagnosed with subsequent NCDs at younger ages compared with those without DM history. Conclusion Our findings contribute to health surveillance and may promote beneficial lifestyle changes in those with early-onset and later-onset DM, which can help prevent subsequent NCDs and improve public health.

Di pasar KPop Indonesia, fan loyalty memainkan peran penting dalam brand ambassador, terutama di industri kecantikan, yang dicontohkan oleh EXO yang mendukung Scarlett Whitening dan Sehun dari EXO untuk Whitelab. Penelitian ini mempelajari dampak fan loyalty dan event marketing terhadap brand image, dengan menganalisis dua event tertentu: "SCARLETT X EXO Glow to You Meet & Greet" dan "Whitelab: One Memorable Day with Scientist Ganteng Oh Sehun." Tanggapan media sosial setelah acara-acara ini memicu ketertarikan, mendorong spekulasi tentang pengaruhnya terhadap brand image. Berfokus pada fandom EXO-L, penelitian ini mengumpulkan data dari 225 responden melalui kuesioner online, dengan menggunakan regresi linier berganda untuk analisis. Hasil penelitian mengungkapkan bahwa fan loyalty dan event marketing secara kolektif memiliki pengaruh yang signifikan terhadap brand image. Menariknya, responden menunjukkan sikap yang lebih positif terhadap Scarlett Whitening dibandingkan dengan Whitelab, menggarisbawahi pentingnya fan loyalty dalam memperkuat brand image melalui event marketing. Penelitian ini mengeksplorasi wawasan tentang peran idol KPop dalam branding, menekankan sinergi antara event marketing dan fan loyalty untuk komunikasi brand yang efektif.

Objective: Cementochronology is a method for assessing chronological age and identifying other life-history parameters (LHPs) from incremental lines of acellular extrinsic fibre cementum (AEFC) in most mammalian teeth. The aim of this study is to question the accuracy of this technique when used as a stand-alone age estimation method, and to examine how the number of observers may alter accuracy. Design: This research is based on an extant clinical study conducted on 10 human teeth with the patients’ anamnestic data. Nine observers used cementochronology to count AEFC incremental lines from 82 digital images. The counting was performed at three non-standardised areas on each image, totalling 246 counts per observer. Resultant observer counts were compared using the coefficient of variation method. Results: The mean deviation of cementum estimated age from known chronological age of the participants in the study is 5.2 years. Conclusion: Our study shows that further critical examination of the current cementochronology technique is essential, due to the subjectivity of line counting. The number of skilled observers in the study may improve the overall accuracy of the technique. These issues have wider implications, as many researchers rely on accurate scientific inferences being made by cementum-based studies to support or refute overarching demographic models and grand evolutionary narratives grounded by life history theory. Until this issue is resolved cementochronology should only be used alongside other age estimation methods.

Abstract Background Black women and people with uteri have utilized collectivistic and relational practices to improve health outcomes in the face of medical racism and discrimination for decades. However, there remains a need for interventions to improve outcomes of uterine fibroids, a condition that disproportionately impacts Black people with uteri. Leveraging personalized approaches alongside evidence that demonstrates the positive impact of social and peer support on health outcomes, we adapted from CenteringPregnancy, an evidence based group prenatal care intervention, for the education and empowerment of patients with uterine fibroids. Methods The present report provides an overview of the study design and planned implementation of CPWF in cohorts at Boston Medical Center and Emory University / Grady Memorial Hospital. After receiving training from the Centering Healthcare Institute (CHI), we adapted the 10-session CenteringPregnancy curriculum to an 8-session hybrid group intervention called Centering Patients with Fibroids (CPWF). The study began in 2022 with planned recruitment of six cohorts of 10-12 participants at each institution. We will conduct a mixed methods evaluation of the program using validated survey tools and qualitative methods, including focus groups and 1:1 interviews. Discussion To date, we have successfully recruited 4 cohorts at Boston Medical Center and are actively implementing BMC Cohort 5 and the first cohort at Emory University / Grady Memorial Hospital. Evaluation of the program is forthcoming.

Abstract The impact of common environmental exposures in combinations with socioeconomic and lifestyle factors on cancer development, particularly for young adults, remains understudied. Here, we leveraged environmental and cancer incidence data collected in New York State at the county level to examine the association between 31 exposures and 10 common cancers (i.e., lung and bronchus, thyroid, colorectal, kidney and renal pelvis, melanoma, non-Hodgkin lymphoma, and leukemia for both sexes; corpus uteri and female breast cancer; prostate cancer), for three age groups (25–49, 50–69, and 70–84 year-olds). For each cancer, we stratified by age group and sex, and applied regression models to examine the associations with multiple exposures simultaneously. The models included 642,013 incident cancer cases during 2010–2018 and found risk factors consistent with previous reports (e.g., smoking and physical inactivity). Models also found positive associations between ambient air pollutants (ozone and PM2.5) and prostate cancer, female breast cancer, and melanoma of the skin across multiple population strata. Additionally, the models were able to better explain the variation in cancer incidence data among 25–49 year-olds than the two older age groups. These findings support the impact of common environmental exposures on cancer development, particularly for younger age groups.

IntroductionAdjuvants added to subunit vaccines augment antigen-specific immune responses. One mechanism of adjuvant action is activation of pattern recognition receptors (PRRs) on innate immune cells. Bordetella colonization factor A (BcfA); an outer membrane protein with adjuvant function, activates TH1/TH17-polarized immune responses to protein antigens from Bordetella pertussis and SARS CoV-2. Unlike other adjuvants, BcfA does not elicit a TH2 response.MethodsTo understand the mechanism of BcfA-driven TH1/TH17 vs. TH2 activation, we screened PRRs to identify pathways activated by BcfA. We then tested the role of this receptor in the BcfA-mediated activation of bone marrow-derived dendritic cells (BMDCs) using mice with germline deletion of TLR4 to quantify upregulation of costimulatory molecule expression and cytokine production in vitro and in vivo. Activity was also tested on human PBMCs.ResultsPRR screening showed that BcfA activates antigen presenting cells through murine TLR4. BcfA-treated WT BMDCs upregulated expression of the costimulatory molecules CD40, CD80, and CD86 and produced IL-6, IL-12/23 p40, and TNF-α while TLR4 KO BMDCs were not activated. Furthermore, human PBMCs stimulated with BcfA produced IL-6. BcfA-stimulated murine BMDCs also exhibited increased uptake of the antigen DQ-OVA, supporting a role for BcfA in improving antigen presentation to T cells. BcfA further activated APCs in murine lungs. Using an in vitro TH cell polarization system, we found that BcfA-stimulated BMDC supernatant supported TFH and TH1 while suppressing TH2 gene programming.ConclusionsOverall, these data provide mechanistic understanding of how this novel adjuvant activates immune responses.

Background and purpose: Information in multiparametric Magnetic Resonance (mpMR) images is relatable to voxel-level tumor response to Radiation Treatment (RT). We have investigated a deep learning framework to predict (i) post-treatment mpMR images from pre-treatment mpMR images and the dose map (“forward models”), and, (ii) the RT dose map that will produce prescribed changes within the Gross Tumor Volume (GTV) on post-treatment mpMR images (“inverse model”), in Breast Cancer Metastases to the Brain (BCMB) treated with Stereotactic Radiosurgery (SRS). Materials and methods: Local outcomes, planning computed tomography (CT) images, dose maps, and pre-treatment and post-treatment Apparent Diffusion Coefficient of water (ADC) maps, T1-weighted unenhanced (T1w) and contrast-enhanced (T1wCE), T2-weighted (T2w) and Fluid-Attenuated Inversion Recovery (FLAIR) mpMR images were curated from 39 BCMB patients. mpMR images were co-registered to the planning CT and intensity-calibrated. A 2D pix2pix architecture was used to train 5 forward models (ADC, T2w, FLAIR, T1w, T1wCE) and 1 inverse model on 1940 slices from 18 BCMB patients, and tested on 437 slices from another 9 BCMB patients. Results: Root Mean Square Percent Error (RMSPE) within the GTV between predicted and ground-truth post-RT images for the 5 forward models, in 136 test slices containing GTV, were (mean ± SD) 0.12 ± 0.044 (ADC), 0.14 ± 0.066 (T2w), 0.08 ± 0.038 (T1w), 0.13 ± 0.058 (T1wCE), and 0.09 ± 0.056 (FLAIR). RMSPE within the GTV on the same 136 test slices, between the predicted and ground-truth dose maps, was 0.37 ± 0.20 for the inverse model. Conclusions: A deep learning-based approach for radiologic outcome-optimized dose planning in SRS of BCMB has been demonstrated.

BackgroundHeart failure with reduced ejection fraction (HFrEF) remains a significant public health issue, with the disease advancing despite neurohormonal antagonism. Energetic dysfunction is a likely contributor to residual disease progression, and we have previously reported a strong association of plasma metabolite profiles with survival among patients with HFrEF. However, the genetic and biologic mechanisms that underlie the metabolite-survival association in HFrEF were uncertain.Methods and resultsWe performed genetic mapping of the key metabolite parameters, followed by mediation analyses of metabolites and genotypes on survival, and genetic pathway analyses. Patients with HFrEF (n = 1,003) in the Henry Ford Pharmacogenomic Registry (HFPGR; 500 self-reported Black/African race patients [AA], 503 self-reported White/European race patients [EA], and 249 deaths over a median of 2.7 years) with genome-wide genotyping and targeted metabolomic profiling of plasma were included. We tested genome-wide association (GWA) of single nucleotide polymorphisms (SNPs) with the prognostic metabolite profile (PMP) and its components; first stratified by race, and then combined via meta-analysis for the entire cohort. Seven independent loci were identified as GWA significant hits in AA patients (3 for PMP and 4 for individual metabolites), one of which was also significant in the entire cohort (rs944469). No genome wide significant hits were found in White/EA patients. Among these SNPs, only rs35792152, (a hit for 3.HBA) tended to be associated with mortality in standard survival analysis (HR = 1.436, p = 0.052). The mediation analyses indicated several significant associations between SNPs, metabolites, and mortality in AA patients. Functional annotation mapping (FUMA) implicated inflammation, DNA metabolic, and mRNA splicing processes.ConclusionsGWAS of key metabolites and survival along with FUMA pathway analysis revealed new candidate genes which unveiled molecular pathways that contribute to HF disease progression via metabolic and energetic abnormalities.

Background Postpartum hypertension is a risk factor for severe maternal morbidity; however, barriers exist for diagnosis and treatment. Remote blood pressure (BP) monitoring programs are an effective tool for monitoring BP and may mitigate maternal health disparities. We aimed to describe and evaluate engagement in a remote BP monitoring program on BP ascertainment during the first 6‐weeks postpartum among a diverse patient population. Methods and Results A postpartum remote BP monitoring program, using cell‐enabled technology and delivered in multiple languages, was implemented at a large safety‐net hospital. Eligible patients are those with hypertensive disorders before or during pregnancy. We describe characteristics of patients enrolled from January 2021 to May 2022 and examine program engagement by patient characteristics. Linear regression models were used to calculate mean differences and 95% CIs between characteristics and engagement metrics. We describe the prevalence of patients with BP ≥140/or >90 mm Hg. Among 1033 patients, BP measures were taken an average of 15.2 days during the 6‐weeks, with the last measurement around 1 month (mean: 30.9 days), and little variability across race or ethnicity. Younger maternal age (≤25 years) was associated with less frequent measures (mean difference, −4.3 days [95% CI: −6.1 to −2.4]), and grandmultiparity (≥4 births) was associated with shorter engagement (mean difference, −3.5 days [95% CI, −6.1 to −1.0]). Prevalence of patients with BP ≥140/or >90 mm Hg was 62.3%, with differences by race or ethnicity (Black: 72.9%; Hispanic: 52.4%; White: 56.0%). Conclusions A cell‐enabled postpartum remote BP monitoring program was successful in uniformly monitoring BP and capturing hypertension among a diverse, safety‐net hospital population.

Objective: RNA-dependent RNA polymerase (RdRp) is a protein that is essential in the replication and transcription processes of SARS-CoV-2. RdRp inhibitors must be sought, particularly in the identification of active substances in herbal or human dietary sources. The purpose of this study was to investigate the molecular docking of phytochemistry from the leaves of Sauropus androgynus against the RdRp protein. Methods: This in silico study was performed using AutoDock Tools 1.5.7, AutoDock Vina v1.2.3 software, and BIOVIA Discovery Studio Visualizer 4.1. Results: Afzelin, kaempferol, and trifolin were found as phytochemistry in Sauropus androgynus leaves. Among the three flavonoid molecules, afzelin has the lowest negative binding affinity (−7.677 kcal/mol), followed by trifolin (−6.906 kcal/mol) and kaempferol (−6.65 kcal/mol). All three flavonoid compounds have a binding affinity that is more negative than the three conventional drugs (favipiravir, remdesivir, ribavirin). Conclusions: Flavonoid from the leaves of Sauropus androgynus leaves can be utilized as candidate for herbal or complementary medicine as an inhbitor of RdRp for COVID-19 treatment.

ABSTRACT Wastewater surveillance has emerged as a crucial public health tool for population-level pathogen surveillance. Supported by funding from the American Rescue Plan Act of 2021, the FDA‘s genomic epidemiology program, GenomeTrakr, was leveraged to sequence SARS-CoV-2 from wastewater sites across the United States. This initiative required the evaluation, optimization, development, and publication of new methods and analytical tools spanning sample collection through variant analyses. Version-controlled protocols for each step of the process were developed and published on protocols.io. A custom data analysis tool and a publicly accessible dashboard were built to facilitate real-time visualization of the collected data, focusing on the relative abundance of SARS-CoV-2 variants and sub-lineages across different samples and sites throughout the project. From September 2021 through June 2023, a total of 3,389 wastewater samples were collected, with 2,517 undergoing sequencing and submission to NCBI under the umbrella BioProject, PRJNA757291. Sequence data were released with explicit quality control (QC) tags on all sequence records, communicating our confidence in the quality of data. Variant analysis revealed wide circulation of Delta in the fall of 2021 and captured the sweep of Omicron and subsequent diversification of this lineage through the end of the sampling period. This project successfully achieved two important goals for the FDA’s GenomeTrakr program: first, contributing timely genomic data for the SARS-CoV-2 pandemic response, and second, establishing both capacity and best practices for culture-independent, population-level environmental surveillance for other pathogens of interest to the FDA.IMPORTANCEThis paper serves two primary objectives. First, it summarizes the genomic and contextual data collected during a Covid-19 pandemic response project, which utilized the FDA’s laboratory network, traditionally employed for sequencing foodborne pathogens, for sequencing SARS-CoV-2 from wastewater samples. Second, it outlines best practices for gathering and organizing population-level next generation sequencing (NGS) data collected for culture-free, surveillance of pathogens sourced from environmental samples.

Abstract Objectives To perform a descriptive analysis of a series of patients with recurrent macroscopic haematuria after a primary standard evaluation including computed tomography urography (CTU) and cystoscopy negative for urinary bladder cancer (UBC) and upper tract urothelial cancer (UTUC) and to identify potential factors associated with occurrence of recurrent macroscopic haematuria. Methods All patients older than 50 years who underwent urological investigation for macroscopic haematuria with both cystoscopy and CTU 2015–2017 were retrospectively reviewed. A descriptive analysis of the primary and later investigations for recurrent macroscopic haematuria was performed. To investigate the association between explanatory variables and the occurrence of recurrent macroscopic haematuria, a Poisson regression analysis was performed. Results A total of 1395 eligible individuals with primary standard investigation negative for UBC and UTUC were included. During a median follow‐up of 6.2 (IQR 5.3–7) years, 248 (18%) patients had recurrent macroscopic haematuria, of whom six patients were diagnosed with UBC, two with prostate cancer, one with renal cell carcinoma and one had a suspected UTUC at the repeated investigation. Within 3 years, 148 patients (11%) experienced recurrent macroscopic haematuria, of whom two patients were diagnosed with low‐grade UBC (TaG1–2), one with T2G3 UBC and one with low‐risk prostate cancer. The presence of an indwelling catheter, use of antithrombotic medication, pathological findings at CTU or cystoscopy or history of pelvic radiotherapy were all statistically significant independent predictors for increased risk for recurrent macroscopic haematuria. Conclusion In the case of recurrent macroscopic haematuria within 3 years of primary standard evaluation for urinary tract cancer, there was a low risk of later urological malignancies in patients initially negative for UBC and UTUC. Therefore, waiting 3 years before conducting another complete investigation in cases of recurrent macroscopic haematuria might be appropriate.

Abstract Sleep disturbances like poor and insufficient sleep are common among medical students in the Middle East and North Africa (MENA) countries; however, the extent of medically defined sleep disorders (SDs) remains unclear. This meta-analysis determines SD prevalence and identifies associated factors among medical students in the MENA. PubMed, Web of Science, Google Scholar, and reference lists of included studies were searched (latest search: June 2022). Meta-analyses included 22 studies and were performed using random-effect models. Included studies used self-reported screening tools for assessing SDs and then estimated the proportion of participants at high risk of developing a SD. Central disorders of hypersomnolence were the most prevalent SD [prevalencepooled range: 30.9% (Jordan) to 62.5% (Saudi Arabia)], followed by insomnia disorders [prevalencepooled range: 30.4% (Jordan) to 59.1% (Morocco)], circadian rhythm sleep–wake disorders [prevalencepooled range: 13.5% (Jordan) to 22.4% (Saudi Arabia)], sleep-related breathing disorders [prevalencepooled range: 12.2% (Jordan) to 22.5% (Pakistan)], sleep-related movement disorders [prevalencepooled range: 5.9% (Egypt) to 30.6% (Saudi Arabia)], and parasomnias [prevalencepooled range: 5.6% (Jordan) to 17.4% (Saudi Arabia)]. Female sex, studying in the latter academic years, having anxiety, excessive internet use, and poor academic performance were significantly associated with SDs. SDs are prevalent among MENA medical students. Implementing student-centered interventions targeting high risk groups in medical schools should be considered to improve students’ health and wellbeing.

Abstract The role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by assessing the role of specific biological domains of PTHrP in tumor progression through stable expression of PTHrP (-36-139aa) or truncated forms with deletion of the nuclear localization sequence (NLS) alone or in combination with the C-terminus. Although the full-length PTHrP molecule (-36-139aa) did not alter tumorigenesis, PTHrP lacking the NLS alone accelerated primary tumor growth by downregulating p27, while PTHrP lacking the NLS and C-terminus repressed tumor growth through p27 induction driven by the tumor suppressor leukemia inhibitory factor receptor (LIFR). Induction of p27 by PTHrP lacking the NLS and C-terminus persisted in bone disseminated cells, but did not prevent metastatic outgrowth, in contrast to the primary tumor site. These data suggest that the PTHrP NLS functions as a tumor suppressor, while the PTHrP C-terminus may act as an oncogenic switch to promote tumor progression through differential regulation of p27 signaling.

Representation of female surgical residents has slowly increased, but underrepresented in medicine (URiM) representation remains disappointingly low. National residency matching reports suggest that meaningful research experience improves surgical residency match success - therefore, formal funding opportunities and early mentorship for URiM medical students. In this study, we catalog medical student (MS) funding opportunities (funding type, eligibility by year, mission, compensation, length of commitment, number of awardees, and dollar investment amount per student) from 7 surgical departments (general surgery, thoracic surgery, vascular surgery, plastic surgery, otorhinolaryngology, orthopedic surgery, neurosurgery) within 196 US medical schools and 20 professional surgical educational organizations through manually searching web pages. We recorded 146 surgical funding opportunities from medical school surgical departments and 16 surgical funding opportunities from professional organizations. Overall, we find that medical institutions' surgical departments and professional surgical educational organizations may not be effectively utilizing recruitment strategies in MS funding opportunities.

Ocean beaches are a major recreational attraction in many coastal cities, requiring accurate visitor counts for infrastructure planning and value estimation. We developed a novel method to assess beach usage on the Gold Coast, Australia, using 507 drone surveys across 24 beaches. The surveys covered 30 km of coastline, accounting for different seasons, times of day, and environmental conditions. Two AI models were employed: one for counting people on land and in water (91–95% accuracy), and another for identifying usage types (85–92% accuracy). Using drone data, we estimated annual beach usage at 34 million people in 2022/23, with 55% on land and 45% in water—approximately double the most recent estimate from lifeguard counts, which are spatially limited and prone to human error. When applying similar restrictions as lifeguard surveys, drone data estimated 15 million visits, aligning closely with lifeguard counts (within 9%). Temporal (time of day, day of the week, season) and spatial (beach location) factors were the strongest predictors of beach usage, with additional patterns explained by weather variables. Our method, combining drones with AI, enhances the coverage, accuracy, and granularity of beach monitoring, offering a scalable, cost-effective solution for long-term usage assessment.

Introduction: In Cerebral Palsy (CP), sensory perception is affected in addition to the motor symptoms. Now-a-days, treatment solely focuses on diagnosed motor deficiencies, often overlooking underlying sensory abnormalities and their examination. Therefore, including a clinical sensory examination in the evaluation of children with CP is crucial. Aim: To develop a validated measure for assessing sensory processing among children with CP. Materials and Methods: This study, conducted as part of a Ph.D. research project, employed an exploratory sequential research design. It commenced on March 1, 2020, and concluded on October 18, 2021, at the Physiotherapy Out Patient Department (OPD) of Swami Vivekanand Subharti University in Meerut, Uttar Pradesh, India. Validity tests, including Scale Level Content Validity Index (CVI) and Spearman rank correlation methods, were used alongside other subtests. The study consisted of two phases: Development and Validation. An extensive literature search and parent interviews were conducted to comprehensively understand and collect information on sensory issues. Based on this information, a preliminary questionnaire draft was created. Three categories of validity-content, face, and concurrent-were tested. Content validation involved employing a three-round online Delphi approach. Face validity was assessed through opinions from clinicians regarding the questionnaire’s appearance. Concurrent validity was established by comparing the Sensory Outcome Measure (SOM) with the criterion measure scale, Short Sensory Profile (SSP). Results: For all items, Content Validity Ratio (CVR) and itemlevel CVI values ranged from 0.8 to 1. The overall Scale Level CVI (average) for the scale was 0.890625. Experts exhibited a 96% agreement regarding the appearance of the questionnaire, indicating complete agreement. The Spearman rank correlation coefficient value was 0.866, and the correlation graph indicated a positive association between the two scales in terms of concurrent validity. Conclusion: The Sensory Outcome Measure (SOM) has been developed as a valid scale with high content and face validity, along with excellent concurrent validity. SOM is the first measuring scale developed in India and used for assessing sensory deficits in children with CP.

IntroductionThis study conducts a bibliometric analysis on neurofeedback research to assess its current state and potential future developments.MethodsIt examined 3,626 journal articles from the Web of Science (WoS) using co-citation and co-word methods.ResultsThe co-citation analysis identified three major clusters: “Real-Time fMRI Neurofeedback and Self-Regulation of Brain Activity,” “EEG Neurofeedback and Cognitive Performance Enhancement,” and “Treatment of ADHD Using Neurofeedback.” The co-word analysis highlighted four key clusters: “Neurofeedback in Mental Health Research,” “Brain-Computer Interfaces for Stroke Rehabilitation,” “Neurofeedback for ADHD in Youth,” and “Neural Mechanisms of Emotion and Self-Regulation with Advanced Neuroimaging.DiscussionThis in-depth bibliometric study significantly enhances our understanding of the dynamic field of neurofeedback, indicating its potential in treating ADHD and improving performance. It offers non-invasive, ethical alternatives to conventional psychopharmacology and aligns with the trend toward personalized medicine, suggesting specialized solutions for mental health and rehabilitation as a growing focus in medical practice.

Objective: In this study, we thoroughly analyzed how balanced the left and right sides of the external acoustic meatus are. Despite previous research focusing on the consistency of various anatomical features and the shape of the external acoustic meatus, which are important for creating guidelines to assess changes in the skull, there hasn't been enough attention given to how symmetrical it is. Our aim was to fill this gap by providing a comprehensive examination of its bilateral symmetry, which is crucial for accurate evaluations in dentistry and medicine. Study design: After importing 26 cone-beam computed tomography scans of patients into the ITK-SNAP 3D imaging software, a midsagittal plane was set up as the plane of symmetry for each patient. With this plane, we compared the positions of the most superior and inferior left and right points of the external acoustic meatus. We also compared the lengths and depths of the lines connecting the two points. Results: There were no statistically significant differences in the position, length, or depth of the external acoustic meatus between the right and left halves of the skull. Conclusion: Specific points on the skull, such as the highest (most superior MSP) and lowest (most inferior MIP) points, demonstrated a high degree of symmetry in the left and right halves. They demonstrated sufficient symmetry to establish a reliable reference plane. Along with the trajectory connecting them, these points can serve as viable alternatives to the Porion for three-dimensional imaging.

Background: Menstruation is an important physiological function of the female reproductive system. The absence of menstruation is called amenorrhea. Many genetic and nongenetic causes are responsible for primary or secondary amenorrhea. This study aimed to determine the types chromosomal abnormalities among patients with primary or secondary amenorrhea. Methods: It was a cross-sectional study conducted in the Department of Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka, from September 2019 to August 2021. A total of 115 women who had come for a karyotype test with complaints of pathological amenorrhea were purposively selected. One hundred five cases presented with primary amenorrhea, and 10 cases presented with secondary amenorrhea. Karyotype analysis in peripheral blood by G-banding was carried out using the standard method. Results: Among the 105 patients with primary amenorrhea, 53.3% of patients had a normal karyotype (46, XX), and 46.6% had chromosomal abnormalities (numerical or structural). Turner syndrome classic, 45, XO (16.2%) and 46, XY DSD (Disorders of Sexual Development) (11.4%) were the two most frequent chromosomal abnormalities found in the patients with primary amenorrhea. Among the 10 cases with secondary amenorrhea, seven patients had normal karyotype, and three patients had chromosomal abnormalities (2 had sex chromosomal abnormalities, and 1 had a structural abnormality of autosome). Conclusion: The study of chromosomal abnormalities will help in the early and accurate diagnosis of the underlying aetiology of primary or secondary amenorrhea. It will also help in the management and proper counselling of cases.

IntroductionExposure to endocrine disrupting chemicals (EDCs), such as phthalates, can negatively impact maternal and child health, contributing to impaired fetal growth, preterm birth, and pregnancy complications, as well as increased downstream risks of cardiometabolic disease and breast cancer. Notably, women of color (WOC) are the largest consumers of personal care products, which are a common source of EDC exposure.MethodsThe Let's Reclaim Our Ancestral Roots (Let's R.O.A.R) Pilot Study developed an educational intervention delivered during pregnancy to promote reduced use of phthalate-containing hair care products (HCPs). This mixed-methods study included: (1) a quantitative analysis and (2) a qualitative analysis of the educational sessions and the semi-structured focus groups to evaluate the factors that influenced the hair care practices and product choices of WOC at various stages of life, including their current pregnancy (hereafter referred to as the hair journey). During the sessions, participants learned about EDCs (with a focus on phthalates), the unequal burden of exposure for WOC, adverse implications of exposure, and exposure reduction strategies. Focus group sessions provided insight into participants' hair journeys from childhood to the current pregnancy and explored factors during their hair product selection process. All sessions were transcribed and imported into NVivo Version 12 for coding and thematic analysis.ResultsA total of 46 individuals were enrolled in the study, and 31 participated in an educational session. This current work synthesizes the qualitative analysis of this study. We identified two important life stages (before and after gaining agency over hair care practices and product choices) and three dominant themes related to HCP use: (1) products that impacted the hair journey, which involved all mentions of hair products, (2) factors that influenced the hair journey, which included individuals or entities that shaped participants' hair experiences, and (3) the relationship between hair and sense of self, where sense of self was defined as the alignment of one's inner and outer beauty.ConclusionThe themes intersected and impacted the participants' hair journey. Cultural integration was a sub-theme that overlapped within the dominant themes and participants discussed the effect of traditions on their hair experiences.

This study investigates the educational implications of the association between social media use and mental well-being in the post-pandemic period. As educational practices increasingly incorporate digital platforms, understanding the impact of students' social media engagement on their mental health is imperative. The role of education in the transformation of information and knowledge within the realm of social media contributes to the significant influences towards individuals’ mental well-being, especially during the COVID-19 pandemic. Education also serves as an instrument of social change to help reduce anxiety of COVID-19 among people. This research, therefore, aimed at investigating the association between social media use and COVID-19 Anxiety and mental well-being among Malaysian adolescents. It focused on the importance of educational implications in the associations among the study variables. Using a convenience sampling technique with a correlational research design, 329 adolescents, 18 to 25 years old, were selected for this study. Social Networking Usage Questionnaire (SNUQ), Coronavirus Anxiety Scale (CAS) and Warwick-Edinburgh Mental Well-being Scale (WEMWBS) were uutilised to measure social media use, anxiety of COVID-19 and mental well-being of the adolescents respectively. Three scales showed high internal consistency with α = .92 for SNUQ, α = .90 for CAS, and α = .94 for WEMWBS. The findings of the study indicated a significant positive association between social media use and COVID-19 anxiety (r = .12, n = 329, p < .05), and a significant positive relationship between social media use and mental well-being (r = .19, n = 329, p < .001). However, results showed an insignificant association between COVID-19 anxiety and mental well-being among adolescents (r = -.051, n = 329, p > .001). The study concluded that the use of social media as a platform for educational transfer and information change abstains from anxiety of COVID-19 and uplifts awareness among Malaysian adolescents on the salient positive influences of it towards their mental health.

Background: A needs assessment identifies the differences between actual and ideal situations to facilitate the development of a new programme or improve existing services. Objectives: This article shares our experiences conducting the needs assessment in a context where people had limited or no understanding of the need being assessed. Method: Adhering to a three-phase model – comprising pre-assessment, assessment, and post-assessment – we employed diverse data collection methods, including quantitative survey, qualitative interviews, and environmental scan. Results: The findings underscored the necessity of expanding rehabilitation services in Ethiopia, with a shift from a purely medical focus to addressing issues associated with daily functioning and community engagement. These issues align closely with the core expertise and responsibilities of occupational therapists. Participants expressed support for the introduction of occupational therapy in Ethiopia and willingness to incorporate the practice of occupational therapists in their settings. The challenges encountered were how to ask about occupational therapy when it is not well known by members of the local population and how to introduce the profession without biasing participants’ responses. Conclusion: Conducting a needs assessment was critical to developing occupational therapy services in Ethiopia. We welcome others to learn from our experiences. Contribution: This manuscript details the assessment process and delves into the challenges we encountered and lessons learned. It extends methodological suggestions to inform future evaluations and contributes valuable insights to the broader discourse on needs assessment and programme development in a context where people have limited awareness of services, such as occupational therapy.

Cells must access resources to survive, and the anatomy of multicellular structures influences this access. In diverse multicellular eukaryotes, resources are provided by internal conduits that allow substances to travel more readily through tissue than they would via diffusion. Microbes growing in multicellular structures, called biofilms, are also affected by differential access to resources and we hypothesized that this is influenced by the physical arrangement of the cells. In this study, we examined the microanatomy of biofilms formed by the pathogenic bacterium Pseudomonas aeruginosa and discovered that clonal cells form striations that are packed lengthwise across most of a mature biofilm's depth. We identified mutants, including those defective in pilus function and in O-antigen attachment, that show alterations to this lengthwise packing phenotype. Consistent with the notion that cellular arrangement affects access to resources within the biofilm, we found that while the wild type shows even distribution of tested substrates across depth, the mutants show accumulation of substrates at the biofilm boundaries. Furthermore, we found that altered cellular arrangement within biofilms affects the localization of metabolic activity, the survival of resident cells, and the susceptibility of subpopulations to antibiotic treatment. Our observations provide insight into cellular features that determine biofilm microanatomy, with consequences for physiological differentiation and drug sensitivity.

Introduction: Polymorphisms in genes responsible for the metabolism and transport of tacrolimus have been demonstrated to influence clinical outcomes for patients following allogeneic hematologic stem cell transplant (allo-HSCT). However, the clinical impact of germline polymorphisms specifically for oral formulations of tacrolimus is not fully described.Methods: To investigate the clinical impact of genetic polymorphisms in CYP3A4, CYP3A5, and ABCB1 on oral tacrolimus pharmacokinetics and clinical outcomes, we prospectively enrolled 103 adult patients receiving oral tacrolimus for the prevention of graft-versus-host disease (GVHD) following allo-HSCT. Patients were followed in the inpatient and outpatient phase of care for the first 100 days of tacrolimus therapy. Patients were genotyped for CYP3A5 *3 (rs776746), CYP3A4 *1B (rs2740574), ABCB1 exon 12 (rs1128503), ABCB1 exon 21 (rs2032582), ABCB1 exon 26 (rs1045642).Results: Expression of CYP3A5 *1 was highly correlated with tacrolimus pharmacokinetics in the inpatient phase of care (p < 0.001) and throughout the entirety of the study period (p < 0.001). Additionally, Expression of CYP3A5 *1 was associated with decreased risk of developing AKI as an inpatient (p = 0.06). Variants in ABCB1 were not associated with tacrolimus pharmacokinetics in this study. We were unable to discern an independent effect of CYP3A4 *1B or *22 in this population.Conclusion: Expression of CYP3A5 *1 is highly influential on the pharmacokinetics and clinical outcomes for patients receiving oral tacrolimus as GVHD prophylaxis following allo-HSCT.

AbstractThe rapid growth and success of sharing economy, particularly e-hailing services, have attracted many organisations to participate in this business. As a result, e-hailing organisations need strategies that enable them to compete in the market. One of the strategies that could help e-hailing organisations to stay competitive is to understand users’ perception of value. The aim of this study is to identify the values that users gain when they use e-hailing services. From there, this study also sought to determine the specific values, which contribute to satisfaction with e-hailing services. The Theory of Consumption Value was applied to examine as users’ perceived value with the inclusion of sustainability value. Based on the Partial Least Squares analysis via the software SmartPLS 3.2.8, users’ perceived value, which consists of economic value, convenience value, sustainability value, and hedonic value positively influences users’ satisfaction, while symbolic value negatively influences users’ satisfaction. The Importance-Performance Matrix Analysis (IPMA) results revealed that hedonic value is the most important value that contributes to users’ satisfaction. Theoretical and managerial implications as well as research limitations are duly discussed.

The aim of this work was to enhance the biological feasibility of a deep convolutional neural network-based in-silico model of neurodegeneration of the visual system by equipping it with a mechanism to simulate neuroplasticity. Therefore, deep convolutional networks of multiple sizes were trained for object recognition tasks and progressively lesioned to simulate neurodegeneration of the visual cortex. More specifically, the injured parts of the network remained injured while we investigated how the added retraining steps were able to recover some of the model’s object recognition baseline performance. The results showed with retraining, model object recognition abilities are subject to a smoother and more gradual decline with increasing injury levels than without retraining and, therefore, more similar to the longitudinal cognition impairments of patients diagnosed with Alzheimer’s disease (AD). Moreover, with retraining, the injured model exhibits internal activation patterns similar to those of the healthy baseline model when compared to the injured model without retraining. Furthermore, we conducted this analysis on a network that had been extensively pruned, resulting in an optimized number of parameters or synapses. Our findings show that this network exhibited remarkably similar capability to recover task performance with decreasingly viable pathways through the network. In conclusion, adding a retraining step to the in-silico setup that simulates neuroplasticity improves the model’s biological feasibility considerably and could prove valuable to test different rehabilitation approaches in-silico.

ABSTRACTAdolescents are the drivers of social change and transformation in any community. Their ability to deal with stressors will determine their well-being and ability to contribute to society. Thus, the present study assessed the relationship between trait emotional intelligence (Trait EI), coping styles, and adolescent stress. In particular, it investigated the role of coping styles as a mediator between Trait EI and adolescent stress. Three hundred fifty-seven adolescents studying in schools in Delhi participated in the study. The study revealed a significant association between Trait EI, coping styles, and adolescent stress. Furthermore, the mediation analysis revealed that the relationship between Trait EI and adolescent stress was partially mediated by emotion-oriented coping style. Task and avoidance-oriented coping did not act as mediators. The current findings have implications for psychologists, school counsellors, and mental health researchers involved in building stress management programs to nurture life skills among adolescents.

The regulation and direction of CD4+ T cells into phenotypic and functional lineages is coordinated by a complex set of mechanisms. Here the authors show a role for Aiolos as a regulator of the CD4+ cytotoxic and T follicular helper lineages.

Abstract Background The COVID-19 pandemic has caused morbidity and mortality, particularly among vulnerable populations. We aimed to assess social and demographic characteristics associated with COVID-19 severity among symptomatic participants during pregnancy. Methods The International Registry of Coronavirus Exposure in Pregnancy is a multinational, longitudinal observational cohort study of adult participants tested for SARS-CoV-2 or who received clinical diagnosis of COVID-19 during pregnancy (NCT04366986). Disease severity status of mild, moderate, or severe was determined based on symptoms and healthcare utilization. Stratified by current versus recent pregnancy at enrollment, univariate mixed-effects logistic regression modeling was used to characterize association between social and demographic characteristics with COVID-19 severity, using a cumulative mixed effect model with country as a random effect. Results The odds of developing more severe COVID-19 (odds ratio [95% confidence interval]) were higher among participants with lower socioeconomic status (poor: 2.72 [2.01,3.69]; lower-middle class: 2.07 [1.62,2.65] vs wealthy), among participants with lower educational attainment (high school: 1.68 [1.39,2.03];

This article starts from a special scientific interest regarding the historical textbooks of the Ladin school in the province of Bolzano. It subjects to a didactic and linguistic analysis the book «Flus de munt» [Mountain flowers], a reading book for primary schools of the Badia valley (South Tyrol), published in three editions between 1967 and 1978. Particularly, the question is asked, what didactic and linguistic relevance this book had and how it influenced the teaching of Ladin in the Ladin school in the years and decades following its publication. From a didactic point of view, it is of great importance to reconstruct with which objectives the book was produced and how this process was perceived by the authors themselves. Instead, from a linguistic point of view, «Flus de munt» stands out as one of the first schoolbooks written entirely in the Ladin language, using two Ladin variants for the same valley: the «Badiotto » and the «Marebbano». Moreover, the book plays a significant role in the development of a (linguistic and cultural) Ladin identity.

Background: Neonatal polycythemia is a condition that is incidentally encountered in clinical practice. It is characterized by elevated hemoglobin levels (above 22 g/dL) and hematocrit ratios above 65%. It is important to understand both the prevalence as well as the related risk factors of this condition as untreated preventable risk factors can result in the development of hyperviscosity syndromes leading to potential multiple organ failure. Prevalence and Risk Factors: Risk factors include the presence of twin-to-twin transfusion, pre-eclampsia, maternal hypertension, operator-dependent cord clamping, and the presence of co-morbid conditions in neonates. The prevalence of neonatal polycythemia varies among regions and factors that may affect this variation include elevation above sea level of the patient and the mother, management of perinatal conditions such as gestational diabetes mellitus, and the method of delivery. Conclusions: From this study, it is evident that not only do existing neonatal and maternal risk factors such as twin-to-twin transfusion syndrome and post-term deliveries, respectively, increase the risk of neonatal polycythemia but also the geographical and socioeconomic status are major factors. It is therefore imperative to conduct more thorough large-scale cohort studies to further understand the reasons for this.

The objective of this study was to assess the factor structure of the 26-item Eating Attitude Test (EAT-26) through confirmatory factor analysis (CFA) among 1,084 undergraduate students in Malaysia. The initial findings indicated a lack of support for the proposed three-factor structure. Model modifications were made due to the inadequate initial fit. The fit of the model was significantly improved by excluding items with factor loadings below 0.40 and integrating residual covariances. In conclusion, it is necessary to make contextual modifications to the EAT-26 in order to effectively utilize it among Malaysian undergraduates. This highlights the significance of cultural adaptations in psychological instruments.

ABSTRACT The inflammasome is essential for host defense against intracellular bacterial pathogens, including Legionella pneumophila, the causative agent of the severe pneumonia Legionnaires’ disease. Inflammasomes recruit and activate caspases, which promote IL-1 family cytokine release and pyroptosis to restrict infection. In mice, interferon (IFN) signaling promotes inflammasome responses against L. pneumophila and other bacteria, in part, through inducing a family of IFN-inducible GTPases known as guanylate-binding proteins (GBPs). Within murine macrophages, IFN promotes the rupture of the L. pneumophila-containing vacuole (LCV), while GBPs are dispensable for vacuole rupture. Instead, GBPs facilitate the lysis of cytosol-exposed L. pneumophila. In contrast, the functions of IFN-γ and GBPs in human inflammasome responses to L. pneumophila are poorly understood. Here, we show that IFN-γ enhances caspase-1- and caspase-4-dependent inflammasome responses to L. pneumophila in human macrophages. We find that human GBP1 is required for these IFN-γ-driven inflammasome responses. Furthermore, we find that GBP1 co-localizes with L. pneumophila and/or LCVs in a type IV secretion system (T4SS)-dependent manner and facilitates damage to the LCV, resulting in increased bacterial access to the host cell cytosol. Our findings reveal species- and pathogen-specific differences in how GBPs function during infection. Importance Inflammasomes are essential for host defense against intracellular bacterial pathogens like Legionella, as they activate caspases, which promote cytokine release and cell death to control infection. In mice, interferon (IFN) signaling promotes inflammasome responses against bacteria by inducing a family of IFN-inducible GTPases known as guanylate-binding proteins (GBPs). Within murine macrophages, IFN promotes the rupture of the Legionella-containing vacuole (LCV), while GBPs are dispensable for this process. Instead, GBPs facilitate the lysis of cytosol-exposed Legionella. In contrast, the functions of IFN and GBPs in human inflammasome responses to Legionella are poorly understood. We show that IFN-γ enhances inflammasome responses to Legionella in human macrophages. Human GBP1 is required for these IFN-γ-driven inflammasome responses. Furthermore, GBP1 co-localizes with Legionella and/or LCVs in a type IV secretion system (T4SS)-dependent manner and promotes damage to the LCV, which leads to increased exposure of the bacteria to the host cell cytosol. Thus, our findings reveal species- and pathogen-specific differences in how GBPs function to promote inflammasome responses.

BackgroundComprehensive and appropriate health care provision to women and girls with female genital mutilation or cutting (FGM/C) is lacking. Use of visuals in health care provider (HCP) consultations facilitates the communication of health information and its comprehension by patients. A web app featuring a 3D visualization of the genitourinary anatomy was developed to support HCPs in conferring clinical information about FGM/C to patients. ObjectiveThe aim of this study was to explore HCP perspectives on the use of visuals in discussion about FGM/C with their patients as well as to obtain their feedback on whether an interactive 3D web app showing the genitourinary anatomy would be helpful in patient consultations about FGM/C, identifying key features that are relevant to their clinical practice. MethodsWe evaluated the web app through a semistructured interview protocol with seven HCPs from various disciplines experienced in care for women and girls with FGM/C in migration-destination settings. Interviews were audio- and video-recorded for transcription, and were then analyzed thematically for contextualized data regarding HCPs’ willingness to use a 3D web app visualizing anatomy in FGM/C consultations with patients. ResultsAll but one of the seven participants expressed keen interest in using this web app and its 3D visuals of anatomy in FGM/C consultations with patients. Participants shared the common contexts for the use of visuals in health care for FGM/C and the concepts they are used to support, such as to help describe a patient’s genitals after FGM/C and reinforce an understanding of clitoral anatomy, to illustrate the process of defibulation, or to explain the physiological effects of FGM/C. Participants also highlighted the benefit of using visuals that patients can relate to, expressing approval for the ability to customize the vulva by FGM/C subtype, skin tone, and complexity of the visual shown in the web app. Despite critiques that the visualization may serve to perpetuate idealistic standards for how a vulva should look, participants largely agreed on the web app’s perceived usefulness to clinical practice and beyond. ConclusionsEvaluation of the web app developed in this study identified that digital tools with 3D models of the genitourinary anatomy that are accessible, informative, and customizable to any specific patient are likely to aid HCPs in communicating clinical information about FGM/C in consultations. Universal access to the web app may be particularly useful for HCPs with less experience in FGM/C. The app also prompts options for applications such as for personal use, in medical education, in patient medical records, or in legal settings. Further qualitative research with patients is required to confirm that adoption of the web app by HCPs in a consultation setting will indeed benefit patient care for women and girls with FGM/C.

Patient outcomes are highly dependent on the accurate and timely receipt of medications. Patient assistance programs (PAPs) provide key medications to uninsured patients at little to no cost. In Texas and our county, nearly 1 in 5 people are uninsured. Approximately 3,500 uninsured patients over the past year have received care from our clinic. PAP applications require various administrative steps to obtain approval for medication assistance, resulting in delays for patients to receive their medications. To combat these delays, we implemented a new electronic system, which has significantly decreased all administrative steps in completing applications.

Natural gas extraction is a critical driver of the economy in western North America. Ecological reclamation is important to ensure surface disturbance impacts associated with natural gas development are not permanent and to assist native biota. Previous studies in semi-arid natural gas fields within Sublette County, Wyoming, USA have shown insects respond favorably to 1–3-year-old well pads undergoing reclamation compared to older successional reference vegetation communities dominated by Wyoming big sagebrush (Artemisia tridentata spp. Wyomingensis). Here, we examined well pads which were initially seed 5, 8, 10, 11, and 12 years prior to our study. We used a free, image-based software called SamplePointv. 1.60 to quantify vegetation on these well pads and adjacent reference areas from cell phone camera photographs. Insects were collected with a sweep net and identified to the family and morphospecies level. Statistical analyses were conducted to compare both vegetation and insect communities between reclamation sites and their paired reference area. We found little statistical difference between vegetation communities across our study but found significantly more insect abundance on reclaimed well pads than reference areas in 3 of 5 years and significantly higher family and morphospecies richness on reclaimed well pads in 4 of 5 years. A total of 2036 individual insects representing 270 species from 71 families across 11 orders were identified across this study. A total of 1557 individuals (76.5%) were found on reclamation sites, whereas 479 (23.5%) were found in reference areas across the entire study. A total of 233 species (86.3% of total) were found on reclamation sites, whereas 121 species (44.8% of total) were found in reference areas across the entire study. A total of 67 families (94.4% of total) were found on reclamation sites, whereas 45 families (63.4% of total) were found in reference areas across the entire study. All 11 orders found in the study were found on reclamation sites, whereas 9 orders were found in reference areas across the entire study. Our results suggest reclamation of natural gas well pads within an old successional stand of sagebrush continues to support higher levels of insect biodiversity and abundance for at least 12 years. As insects are the most diverse group of animals on Earth and because they provide a wide array of ecosystem services, our findings suggest ecological reclamation plays an important role in returning biodiversity and ecosystem functionality to a semi-arid and old successional sagebrush–steppe ecosystem.

OBJECTIVES/GOALS: The objective of this research was to determine the associations of candidate genetic variants withdrug-induced long QT syndrome (diLQTS) risk, an adverse effect of over 150 FDA-approved drugsthat can lead to cardiac arrhythmias and sudden cardiac death. METHODS/STUDY POPULATION: This was a retrospective observational study of the genomic biobank at the University of Michigan Health System. Patients treated with a high-risk QT-prolonging drug and ECG measurements were included. The primary outcome was exaggerated prolongation of the QTc interval (i.e., >60 ms change from baseline and/or >500 ms absolute value) corrected using Bazett. We analyzed 3 genetic variants: KCNE1-D85N (rs1805128), SCN5A-G615E (rs12720452) and KCNE2-I57T (rs7415448) in the dominant genetic model. A Bonferroni-corrected p-value of 0.017 was considered statistically significant using logistic regression adjusted for clinical covariates. RESULTS/ANTICIPATED RESULTS: In total 6,083 self-reported white patients were included (12% event rate). The adjusted odd ratio for KCNE1-D85N was 2.24 (95%CI: 1.35-3.57; p=0.0011). The adjusted odds ratio forKCNE2-I57T was 1.40 (95%CI: 0.26-5.78, p=0.662). Only 4 total patients carried the SCN5A-G615E variant, and none of the carriers had prolonged QTc. DISCUSSION/SIGNIFICANCE: This is the largest study of candidate genetic variants in cardiac ion channels associated with the diLQTS risk. KCNE1-D85N was associated with diLQTS risk, while KCNE2-I57T was suggestive of a potential association. KCNE1-D85N should be considered in clinical guidelines as a risk factor of diLQTS.

Cross-sectional surveys have found variations in how prepared medical students feel to prescribe antibiotics responsibly, but insights are lacking on the stability of these outcomes. In a 2015 survey, final-year Swedish medical students reported very high preparedness levels across a comprehensive range of relevant curriculum topics. We repeated this survey in 2021 to assess the stability of previous findings and to capture the potential impacts of the COVID-19 pandemic. Final-year students in 2015 and 2021 at all seven Swedish medical schools were eligible to participate in an online survey covering curricula topics, teaching methods and COVID-19 impacts (2021). Eligible students received email invitations and reminders from local coordinators. Students from six of seven medical schools participated in both surveys, with response rates of 24.1% (309/1281) in 2021 and 21.3% (239/1124) in 2015. The average global preparedness was 77.0% and 83.2%, respectively (p < 0.001), with lower preparedness levels in 24/27 curriculum topics in 2021. Students at certain universities reported COVID-19 impacts on antibiotic prescribing education (format, duration and perceived quality). Self-reported preparedness levels have fallen slightly but remain high compared with 2015 levels in other European countries. Students consistently reported lower preparedness in specific topics; improvement efforts should consider focusing on these areas, particularly in the context of the ongoing implementation of programmes leading to a full licence upon graduation.