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Introduction: Patients with long bone fractures often present to the emergency department (ED) with severe pain and are typically treated with opioid and non-opioid analgesics. Historical data reveals racial disparities in analgesic administration, with White patients more likely to receive analgesics. With the diversifying US population, health equity is increasingly crucial. In this study we aimed to evaluate the early administration of opioid and non-opioid analgesia among Black and White patients with long bone and femur fractures in EDs over different time frames using a substantial database.Methods: We retrospectively extracted Information from 57 US healthcare organizations within the TriNetX database, encompassing 95 million patients. The ED records from 2003–2023 were subjected to propensity score matching for age and gender. We focused on four cohorts: two comprising Black and White patients diagnosed with long bone fractures, and another two with Black and White patients diagnosed solely with femur fractures. We examined analgesic administration rates over 20 years (2003–2023) at five-year intervals (2003–2008; 2008–2013; 2013–2018; 2018–2023), and further analyzed the rates for the most recent two-year period (2021–2023).Results: Disparities in analgesic administration significantly diminished over the study period. For patients with long bone fractures (1,095,052), the opioid administration gap narrowed from 6.3% to 1.1%, while non-opioid administration disparities reduced from 4.4% to 0.3%. Similar trends were noted for femur fractures (265,181). By 2021–2023, no significant differences in analgesic administration were observed between racial groups.Conclusion: Over the past 20 years, the gap in early administration of opioid and non-opioid analgesics for Black and White patients presenting with long bone fractures or femur fractures has been disappearing.

PurposeLong COVID-19 syndrome occurs in 10-20 % of people after a confirmed/probable SARS-COV-2 infection; new symptoms begin within three months of COVID-19 diagnosis and last > 8 weeks. Little is known about risk factors for long COVID, particularly in older people who are at greater risk of COVID complications.MethodsData are from Women's Health Initiative (WHI) postmenopausal women who completed COVID surveys that included questions on whether they had ever been diagnosed with COVID and length and nature of symptoms. Long COVID was classified using standard consensus criteria. Using WHI demographic and health data collected at study enrollment (1993-98) through the present day, machine learning identified the top 20 risk factors for long COVID. These variables were tested in logistic regression models.ResultsOf n = 37,280 survey respondents, 1237 (mean age = 83 years) reported a positive COVID-19 test and 425 (30 %) reported long COVID. Symptoms included an array of neurological, cardio-pulmonary, musculoskeletal, and general fatigue, and malaise symptoms. Long COVID risk factors included weight loss, physical and mobility limitations, and specific heath conditions (e.g., history of heart valve procedure, rheumatoid arthritis).ConclusionsKnowledge of risk factors for long COVID may be the first step in understanding the etiology of this complex disease.

Monitoring and supporting teachers in the classroom, as well as the implementation of curriculum changes, pose problems in South Africa. This is due to an array of challenges such as a lack of resources, communication barriers within the Department of Basic Education (DBE) as well as a lack of proper infrastructure. In the research reported on here we investigated the challenges that curriculum advisors in the Vhembe-West district face and provides insight into some of their daily challenges. This could assist the international platform, especially as developing countries and other Third World Countries can benefit from the outcomes of this research. A qualitative research approach was used where 12 interviews were conducted with curriculum advisors in the Vhembe-West district. The interview questions were e-mailed to them beforehand so that they could familiarise themselves with the questions to be answered. Within a period of 2 weeks thereafter, interviews were conducted and recorded for analysis on Zoom or Microsoft Teams. The data were grouped and are presented in 5 different themes with the aim of highlighting the challenges as well as providing recommendations to deal with the challenges that curriculum advisors experience. The data reveal that curriculum advisors experience that they receive minimal support from their superiors and that the resources at their disposal also prove to be minimal. This study highlights the lack of resources, insufficient infrastructure, and lack of effective communication from management needed for proper curriculum implementation at schools.

Chronic kidney disease (CKD) impacts about 1 in 7 adults in the United States, but African Americans (AAs) carry a disproportionately higher burden of disease. Epigenetic modifications, such as DNA methylation at cytosine-phosphate-guanine (CpG) sites, have been linked to kidney function and may have clinical utility in predicting the risk of CKD. Given the dynamic relationship between the epigenome, environment, and disease, AAs may be especially sensitive to environment-driven methylation alterations. Moreover, risk models incorporating CpG methylation have been shown to predict disease across multiple racial groups. In this study, we developed a methylation risk score (MRS) for CKD in cohorts of AAs. We selected nine CpG sites that were previously reported to be associated with estimated glomerular filtration rate (eGFR) in epigenome-wide association studies to construct a MRS in the Hypertension Genetic Epidemiology Network (HyperGEN). In logistic mixed models, the MRS was significantly associated with prevalent CKD and was robust to multiple sensitivity analyses, including CKD risk factors. There was modest replication in validation cohorts. In summary, we demonstrated that an eGFR-based CpG score is an independent predictor of prevalent CKD, suggesting that MRS should be further investigated for clinical utility in evaluating CKD risk and progression.

Abstract Background Acute ankle sprains represent one of the most common traumatic injuries to the musculoskeletal system. Many individuals with these injuries experience unresolved symptoms such as instability and recurrent sprains, leading to chronic ankle instability (CAI), which affects their ability to maintain an active lifestyle. While rehabilitation programs focusing on sensorimotor, neuromuscular, strength and balance training are primary treatments, some patients require surgery when rehabilitation fails. A critical analysis of the patient-reported outcome tools (PROs) used to assess CAI surgical outcomes raises some concerns about their measurement properties in CAI patients, which may ultimately affect the quality of evidence supporting current surgical practice. The aim of this research is to develop and validate a new PRO for the assessment of ankle instability and CAI treatment outcomes, following recent methodological guidelines, with the implicit aim of contributing to the generation of scientifically meaningful evidence for clinical practice in patients with ankle instability. Methods Following the COnsensus-based Standards for the selection of Health Measurement Instruments (COSMIN), an Ankle Instability Treatment Index (AITI) will be developed and validated. The process begins with qualitative research based on face‒to‒face interviews with CAI individuals to explore the subjective experience of living with ankle instability. The data from the interviews will be coded following an inductive approach and used to develop the AITI content. The preliminary version of the scale will be refined through an additional round of face‒to‒face interviews with a new set of CAI subjects to define the AITI content coverage, relevance and clarity. Once content validity has been examined, the AITI will be subjected to quantitative analysis of different measurement properties: construct validity, reliability and responsiveness. Discussion The development of AITI aims to address the limitations of existing instruments for evaluating surgical outcomes in patients with CAI. By incorporating patient input and adhering to contemporary standards for validity and reliability, this tool seeks to provide a reliable and meaningful assessment of treatment effects. Trial registration Not applicable.

Introduction: Patients with long bone fractures often present to the emergency department (ED) with severe pain and are typically treated with opioid and non-opioid analgesics. Historical data reveals racial disparities in analgesic administration, with White patients more likely to receive analgesics. With the diversifying US population, health equity is increasingly crucial. In this study we aimed to evaluate the early administration of opioid and non-opioid analgesia among Black and White patients with long bone and femur fractures in EDs over different time frames using a substantial database. Methods: We retrospectively extracted Information from 57 US healthcare organizations within the TriNetX database, encompassing 95 million patients. The ED records from 2003–2023 were subjected to propensity score matching for age and gender. We focused on four cohorts: two comprising Black and White patients diagnosed with long bone fractures, and another two with Black and White patients diagnosed solely with femur fractures. We examined analgesic administration rates over 20 years (2003–2023) at five-year intervals (2003–2008; 2008–2013; 2013–2018; 2018–2023), and further analyzed the rates for the most recent two-year period (2021–2023). Results: Disparities in analgesic administration significantly diminished over the study period. For patients with long bone fractures (1,095,052), the opioid administration gap narrowed from 6.3% to 1.1%, while non-opioid administration disparities reduced from 4.4% to 0.3%. Similar trends were noted for femur fractures (265,181). By 2021–2023, no significant differences in analgesic administration were observed between racial groups. Conclusion: Over the past 20 years, the gap in early administration of opioid and non-opioid analgesics for Black and White patients presenting with long bone fractures or femur fractures has been disappearing.

Abstract Chronic kidney disease (CKD) impacts about 1 in 7 adults in the United States, but African Americans (AAs) carry a disproportionately higher burden of disease. Epigenetic modifications, such as DNA methylation at cytosine-phosphate-guanine (CpG) sites, have been linked to kidney function and may have clinical utility in predicting the risk of CKD. Given the dynamic relationship between the epigenome, environment, and disease, AAs may be especially sensitive to environment-driven methylation alterations. Moreover, risk models incorporating CpG methylation have been shown to predict disease across multiple racial groups. In this study, we developed a methylation risk score (MRS) for CKD in cohorts of AAs. We selected nine CpG sites that were previously reported to be associated with estimated glomerular filtration rate (eGFR) in epigenome-wide association studies to construct a MRS in the Hypertension Genetic Epidemiology Network (HyperGEN). In logistic mixed models, the MRS was significantly associated with prevalent CKD and was robust to multiple sensitivity analyses, including CKD risk factors. There was modest replication in validation cohorts. In summary, we demonstrated that an eGFR-based CpG score is an independent predictor of prevalent CKD, suggesting that MRS should be further investigated for clinical utility in evaluating CKD risk and progression.

ObjectivesNonalcoholic fatty liver disease is the most common chronic liver disease in children. Elafibranor, a dual peroxisome proliferator-activated receptor α/δ agonist, has been proposed as a treatment for nonalcoholic steatohepatitis (NASH). The aims were to (1) describe pharmacokinetics (PK), safety, and tolerability of oral elafibranor at 2 doses (80 and 120 mg) in children 8-17 years and (2) assess changes in aminotransferases.MethodsChildren with NASH were randomized to open-label elafibranor 80 mg or 120 mg daily for 12 weeks. The intent-to-treat analysis included all participants who received at least 1 dose. Standard descriptive statistics and PK analyses were performed.ResultsTen males [mean 15.1 years, standard deviation (SD) 2.2] with NASH were randomized to 80 mg (n = 5) or 120 mg (n = 5). Baseline mean alanine aminotransferase (ALT) was 82 U/L (SD 13) and 87 U/L (SD 20) for 80 mg and 120 mg groups, respectively. Elafibranor was rapidly absorbed and well tolerated. Elafibranor plasma exposure increased between the 80 mg and 120 mg dose with a 1.9- and 1.3-fold increase in median Cmax and AUC 0-24 , respectively. End of treatment mean ALT was 52 U/L (SD 20) for the 120 mg group, with a relative mean ALT change from baseline of -37.4% (SD 23.8%) at 12 weeks.ConclusionsOnce daily dosing of elafibranor was well tolerated in children with NASH. There was a 37.4% relative reduction from mean baseline ALT in the 120 mg group. Decreasing ALT may be associated with improvement in liver histology, thus could be considered a surrogate for histology in early phase trials. These results may support further exploration of elafibranor in children with NASH.

Abstract Background The advancement of sequencing technologies results in the rapid release of hundreds of new genome assemblies a year providing unprecedented resources for the study of genome evolution. Within this context, the significance of in-depth analyses of repetitive elements, transposable elements (TEs) in particular, is increasingly recognized in understanding genome evolution. Despite the plethora of available bioinformatic tools for identifying and annotating TEs, the phylogenetic distance of the target species from a curated and classified database of repetitive element sequences constrains any automated annotation effort. Moreover, manual curation of raw repeat libraries is deemed essential due to the frequent incompleteness of automatically generated consensus sequences. Results Here, we present an example of a crowd-sourcing effort aimed at curating and annotating TE libraries of two non-model species built around a collaborative, peer-reviewed teaching process. Manual curation and classification are time-consuming processes that offer limited short-term academic rewards and are typically confined to a few research groups where methods are taught through hands-on experience. Crowd-sourcing efforts could therefore offer a significant opportunity to bridge the gap between learning the methods of curation effectively and empowering the scientific community with high-quality, reusable repeat libraries. Conclusions The collaborative manual curation of TEs from two tardigrade species, for which there were no TE libraries available, resulted in the successful characterization of hundreds of new and diverse TEs in a reasonable time frame. Our crowd-sourcing setting can be used as a teaching reference guide for similar projects: A hidden treasure awaits discovery within non-model organisms.

BackgroundRacial and ethnic disparities in COVID-19 risk are well-documented; however, few studies in older adults have examined multiple factors related to COVID-19 exposure, concerns, and behaviors or conducted race- and ethnicity- stratified analyses. The Women's Health Initiative (WHI) provides a unique opportunity to address those gaps.MethodsWe conducted a secondary analysis of WHI data from a supplemental survey of 48,492 older adults (mean age 84 years). In multivariable-adjusted modified Poisson regression analyses, we examined predisposing factors and COVID-19 exposure risk, concerns, and behaviors. We hypothesized that women from minoritized racial or ethnic groups, compared to Non-Hispanic White women, would be more likely to report: exposure to COVID-19, a family or friend dying from COVID-19, difficulty getting routine medical care or deciding to forego care to avoid COVID-19 exposure, and having concerns about the COVID-19 pandemic.ResultsAsian women and Non-Hispanic Black/African American women had a higher risk of being somewhat/very concerned about risk of getting COVID 19 compared to Non-Hispanic White women and each were significantly more likely than Non-Hispanic White women to report forgoing medical care to avoid COVID-19 exposure. However, Asian women were 35% less likely than Non-Hispanic White women to report difficulty getting routine medical care since March 2020 (aRR 0.65; 95% CI 0.57, 0.75).ConclusionsWe documented COVID-related racial and ethnic disparities in COVID-19 exposure risk, concerns, and care-related behaviors that disfavored minoritized racial and ethnic groups, particularly Non-Hispanic Black/African American women.

The surgical management of posterior cruciate ligament (PCL) injuries can be challenging. As most PCL injuries occur in a flexed knee position, the anterolateral bundle is thought to be more commonly injured than the posteromedial bundle (PMB); however, in hyperextension, the PMB plays a more significant role. The smaller size of the PMB compared with the anterolateral bundle and its lower strength may explain why isolated hyperextension PMB injuries can be easily overlooked. In this Technical Note, a surgical technique to perform a nonanatomic PMB augmentation of the PCL using a gracilis tendon autograft or allograft is reported. These technical features aim to overcome current limitations in existing techniques to address the symptoms after partial PCL hyperextension injuries.

We present a genome assembly from an individual female Vipera ursinii rakosiensis (the Hungarian meadow viper; Chordata; Lepidosauria; Squamata; Viperidae). The genome sequence is 1,625.0 megabases in span. Most of the assembly is scaffolded into 19 chromosomal pseudomolecules, including the W and Z sex chromosomes. The mitochondrial genome has also been assembled and is 17.38 kilobases in length.