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The association between late replication timing and low transcription rates in eukaryotic heterochromatin is well-known, yet the specific mechanisms underlying this link remain uncertain. In Saccharomyces cerevisiae , the histone deacetylase Sir2 is required for both transcriptional silencing and late replication at the repetitive ribosomal DNA arrays (rDNA). We have previously reported that in the absence of SIR2 , a derepressed RNA PolII repositions MCM replicative helicases from their loading site at the ribosomal origin, where they abut well-positioned, high-occupancy nucleosomes, to an adjacent region with lower nucleosome occupancy. By developing a method that can distinguish activation of closely spaced MCM complexes, here we show that the displaced MCMs at rDNA origins have increased firing propensity compared to the nondisplaced MCMs. Furthermore, we found that both, activation of the repositioned MCMs and low occupancy of the adjacent nucleosomes critically depend on the chromatin remodeling activity of FUN30 . Our study elucidates the mechanism by which Sir2 delays replication timing, and it demonstrates, for the first time, that activation of a specific replication origin in vivo relies on the nucleosome context shaped by a single chromatin remodeler.

Herein, we present a comprehensive total synthesis of cannabidiol integrating both batch and continuous flow conditions. Our approach is planned to streamline the synthesis of olivetolic acid derivatives and utilize an enantiomerically pure monoterpene moiety obtained from naturally occurring (R)-(+)-limonene by photocatalysis. Key reactions, including the synthesis of olivetolic ester and a Friedel-Crafts alkylation, are successfully adapted to continuous flow, resulting in improved yields and selectivities. This study not only offers a scalable and efficient route for cannabidiol synthesis but also contributes to the synthetic approaches to access cannabinoids (diversity synthesis), with potential applications in medicinal and industrial contexts., (© 2024 Wiley-VCH GmbH.)

Background: The appearance of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) initiated the COVID-19 pandemic, resulting in millions of confirmed cases and numerous fatalities. In response, rapid vaccine development efforts were launched to mitigate the pandemic's impact. Despite the high efficacy of COVID-19 vaccines, they are also associated with several common side effects/complications, some of them specific to the multiple sclerosis population. Our goal is to review various types of COVID-19 vaccines, assessing their efficacy, adverse events, their association with an MS relapse following vaccination, and the influence of disease modifying therapies (DMTs) on vaccines' efficacy., Methods: The review was based on a database search that included PubMed/Medline, Embase, Scopus, and the Web of Science conducted from January 2020 to July 2024 using the following MeSH terms: MS, COVID-19, COVID-19 vaccination, vaccine side effects, and vaccine hesitancy., Results: Receiving any type of COVID-19 vaccine is a safer and more reliable approach to building immunity compared to becoming infected with the virus. Complications tend to be mild to moderate, occasionally severe. DMTs could affect the humoral response to the COVID-19 vaccine. Among all DMTs, a notable reduction in the humoral response has been observed in patients who received anti-CD20 and sphingosine-1-phosphate (S1P) receptor modulator drugs after their COVID-19 vaccination., Conclusion: Despite certain drawbacks, the benefits of the COVID-19 vaccine significantly outweigh the associated risks, making it a recommended course of action for people with multiple sclerosis (pwMS). However, physicians need to be mindful of potential complications especially in patients undergoing anti CD20 and manage them appropriately., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

In ecological contexts natural selection might favor individuals with a larger body mass to monopolize resources; however, there is wide variation in body mass within populations and potential factors. In this study, we evaluated whether fruit production limits body mass in one group of Sapajus apella, its effects on behavior, and whether there is a relationship between social status and body mass. We recorded activity patterns using focal follows (20 min), body mass (using a modified Ohaus scale), and community wide fruit production estimates (from 60 fruit traps). Body mass remained relatively stable during periods of food scarcity, but in periods of abundance most individuals gained weight, as indicated by their relative growth rates (RGR). Subordinate subadults showed the highest RGR, as expected by their age. In periods of high fruit production activities as traveling, grooming, and playing were more frequent than during fruit scarcity, suggesting energy maximization and potential energetic constraints. We found differences in behavior within the group, as the alpha male was observed feeding more frequently (and for longer periods of time), was more aggressive (e.g., feeding trees), and received more grooming than other individuals. In addition, the alpha male was 60% heavier than the group's average body mass. Our study supports the hypothesis that body weight gain is related to fruit abundance and that body size is associated with social dominance; however, large individuals (both males and females) seem to incur in high metabolic or reproductive costs, as they do not gain much weight as smaller individuals., (© 2024 Wiley Periodicals LLC.)

Cardiovascular disease (CVD) poses a significant health burden, particularly among individuals of low socioeconomic status (SES) in low- and middle-income countries (LMICs). This study evaluates the clinical effectiveness of cardiac rehabilitation (CR) in addressing CVD outcomes among very low-SES patients in Colombia. Data from participants enrolled in a CR program in Colombia between 2022 and 2023 were analyzed retrospectively. Measures included heart-healthy behaviors, physical/psychological outcomes, and quality of life assessed at 18, 36, and 60 sessions. Significant improvements were observed in exercise capacity, psychological well-being, and quality of life metrics throughout the CR program. However, barriers to CR attendance and the critical need for expanded program availability remain evident, particularly in LMIC settings like Colombia. In conclusion, structured CR programs demonstrate substantial benefits for very low-SES individuals in a LMIC country, highlighting the urgent need for increased program accessibility and equitable healthcare provision to optimize cardiovascular health outcomes.

School nurses (SNs) practicing in DC public and public charter schools were surveyed to assess their perceived role and self-reported preparation to provide behavioral health prevention, early identification, and treatment services in schools. A total of 154 SNs completed a questionnaire about their role in the delivery of behavioral health services and supports. SNs reported they are primarily involved in the identification and referral of students to other school behavioral health professionals. Respondents also reported a lack of training in behavioral health and a desire for more information on related programs and services. This study offers recommendations for educating future SNs and highlights how the DC School Health Services Program utilized study findings to build capacity for SNs employed in practice. This study can help tailor educational opportunities for SNs to maximize their role in school behavioral healthcare process flows and ultimately improve outcomes for students and families., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

In East Africa, community-based conservation models (CBCMs) have been established to support the conservation of wildlife in fragmented landscapes like the Tarangire Ecosystem, Tanzania. To assess how different management approaches maintained large herbivore populations, we conducted line distance surveys and estimated seasonal densities of elephant, giraffe, zebra, and wildebeest in six management units, including three CBCMs, two national parks (positive controls), and one area with little conservation interventions (negative control). Using a Monte-Carlo approach to propagate uncertainties from the density estimates and trend analysis, we analyzed the resulting time series (2011-2019). Densities of the target species were consistently low in the site with little conservation interventions. In contrast, densities of zebra and wildebeest in CBCMs were similar to national parks, providing evidence that CBCMs contributed to the stabilization of these migratory populations in the central part of the ecosystem. CBCMs also supported giraffe and elephant densities similar to those found in national parks. In contrast, the functional connectivity of Lake Manyara National Park has not been augmented by CBCMs. Our analysis suggests that CBCMs can effectively conserve large herbivores, and that maintaining connectivity through CBCMs should be prioritized., (© 2024. The Author(s).)

With the improvement in survival of patients undergoing knee reconstructive surgeries, the functional parameter became widely studied heading optimize and minimize motor sequelae. In patients undergoing knee endoprosthesis, proximal tibial or distal femoral resections affect the functioning of the knee extensor mechanism, with possible repercussions on gait. Seventeen patients were selected, divided into two groups, undergoing distal femoral or proximal tibial resection, and gait analysis examination was performed. Changes in gait velocity, cadence, step length, and alterations in the support and balance phase were observed. No major statistically significant differences were found in the kinetic and kinematic parameters between the operated groups. The study corroborates that although tibial resections have a higher theoretical risk of compromising the extensor mechanism, such data were not observed in the analyzed sample., (© 2024. The Author(s), under exclusive licence to Istituto Ortopedico Rizzoli.)

Objective: The authors report no conflicts of interest.To determine baseline sleep characteristics of male/female student-athletes across multiple sports using objective and subjective measures., Design: Prospective study., Setting: Division I college., Participants: Eighty-two male and female Division I student-athletes., Interventions: Participants completed 2 validated sleep questionnaires (Epworth Sleepiness Scale [ESS] and Single-Item Sleep Quality Scale [SISQS]) to assess subjective sleep. They also wore a validated sleep monitoring device (WHOOP 4.0 band) for at least 14 nights to collect objective data on total sleep time (TST) and sleep architecture., Main Outcome Measures: Overnight sleep variables, including TST, time spent awake in bed after falling asleep, time spent in light sleep, rapid eye movement (REM) sleep, and slow-wave sleep (SWS) cycles. Sleep quality and daytime sleepiness were also assessed., Results: There were no statistical differences between male and female student-athletes in average TST, sleep architecture, sleep consistency, SISQS, and ESS scores. The average TST was 409.2 ± 36.3 minutes. Sleep architecture consisted of 25.6% REM, 19.9% SWS, and 54.4% light sleep. The average sleep consistency was 61.6% ± 8.9%. The average SISQS score was 6.48 ± 1.71, and the average ESS score was 7.57 ± 3.82. A significant difference was found in average wake time between males and females (55.0 vs 43.7 min, P = 0.020), with an overall average of 50.2 ± 16.2 minutes., Conclusions: College student-athletes do not typically obtain the recommended amount of sleep. Optimizing sleep can positively affect academic and athletic performance., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The management of elderly acetabular fractures is complex, with high rates of conversion total hip arthroplasty (THA) after open reduction and internal fixation (ORIF), but potentially higher rates of complications after acute THA., Methods: The California Office of Statewide Health Planning and Development database was queried between 2010 and 2017 for all patients aged 60 years or older who sustained a closed, isolated acetabular fracture and underwent ORIF, THA, or a combination. Chi-square tests and Student t tests were used to identify demographic differences between groups. Multivariate regression was used to evaluate predictors of 30-day readmission and 90-day complications. Kaplan-Meier (KM) survival analysis and Cox proportional hazards model were used to estimate the revision surgery-free survival (revision-free survival [RFS]), with revision surgery defined as conversion THA, revision ORIF, or revision THA., Results: A total of 2,184 surgically managed acetabular fractures in elderly patients were identified, with 1,637 (75.0%) undergoing ORIF and 547 (25.0%) undergoing THA with or without ORIF. Median follow-up was 295 days (interquartile range, 13 to 1720 days). 99.4% of revisions following ORIF were for conversion arthroplasty. Unadjusted KM analysis showed no difference in RFS between ORIF and THA (log-rank test P = 0.27). RFS for ORIF patients was 95.1%, 85.8%, 78.3%, and 71.4% at 6, 12, 24 and 60 months, respectively. RFS for THA patients was 91.6%, 88.9%, 87.2%, and 78.8% at 6, 12, 24 and 60 months, respectively. Roughly 50% of revisions occurred within the first year postoperatively (49% for ORIF, 52% for THA). In propensity score-matched analysis, there was no difference between RFS on KM analysis ( P = 0.22)., Conclusions: No difference was observed in medium-term RFS between acute THA and ORIF for elderly acetabular fractures in California. Revision surgeries for either conversion or revision THA were relatively common in both groups, with roughly half of all revisions occurring within the first year postoperatively., Level of Evidence: III., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Purpose: Ankle arthrodesis is a mainstay of surgical management for ankle arthritis. Accurately risk-stratifying patients who undergo ankle arthrodesis would be of great utility. There is a paucity of accurate prediction models that can be used to pre-operatively risk-stratify patients for ankle arthrodesis. We aim to develop a predictive model for major perioperative complication or readmission after ankle arthrodesis., Methods: This is a retrospective cohort study of adult patients who underwent ankle arthrodesis at any non-federal California hospital between 2015 and 2017. The primary outcome is readmission within 30 days or major perioperative complication. We build logistic regression and ML models spanning different classes of modeling approaches, assessing discrimination and calibration. We also rank the contribution of the included variables to model performance for prediction of adverse outcomes., Results: A total of 1084 patients met inclusion criteria for this study. There were 131 patients with major complication or readmission (12.1%). The XGBoost algorithm demonstrates the highest discrimination with an area under the receiver operating characteristic curve of 0.707 and is well-calibrated. The features most important for prediction of adverse outcomes for the XGBoost model include: diabetes, peripheral vascular disease, teaching hospital status, morbid obesity, history of musculoskeletal infection, history of hip fracture, renal failure, implant complication, history of major fracture., Conclusion: We report a well-calibrated algorithm for prediction of major perioperative complications and 30-day readmission after ankle arthrodesis. This tool may help accurately risk-stratify patients and decrease likelihood of major complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc), which leads to motor and non-motor symptoms (NMS). NMS can appear many years before the classical motor symptoms and are associated with the neurodegeneration of several nuclei; in this work, we highlight the neurodegeneration of Locus coeruleus (LC) in PD. The aim was to investigate the effects of depleting SNpc and LC catecholaminergic neurons on behavioral and neurobiological endpoints. Here we used 6-hydroxydopamine (6-OHDA) in order to induced neurotoxic damage in three independent experimental groups: SNpc lesion group, which 6-OHDA was injected into CPu (CPu-6-OHDA), LC lesion group, which 6-OHDA was injected directly on LC to selectively caused a damage on this nucleus (LC-6-OHDA), and the combined SNpc and LC lesion group (CL-6-OHDA). Next, the behavioral studies were performed using the Morris water maze (MWM), open field (OF), and elevated plus maze (EPM). After stereotaxic surgeries, the animals showed a loss of 67% and 77% of Tyrosine hydroxylase (TH) reactive neurons in the SNpc and LC, respectively. The behavioral analysis showed the anxiety-like behavior in CL-6-OHDA group in the EPM test; in the MWM test, the combined lesions (CL-6-OHDA) showed an impairment in memory acquisition and spatial memory; and no changes were observed in locomotor activity in all the tests. Furthermore, our investigation demonstrating the effects of depleting SN and LC catecholaminergic neurons on behavioral and neurobiological parameters. All these data together lead us to believe that a bilateral PD model including a LC bilateral degeneration is potentially a more accurate model to evaluate the NMS in the pathological development of the disease in rodents., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The longevity of current joint replacements is limited by aseptic loosening, which is the primary cause of non-infectious failure for hip, knee, and ankle arthroplasty. Aseptic loosening is typically caused either by osteolysis from particulate wear, or by high shear stresses at the bone-implant interface from over-constraint. Our objective was to demonstrate feasibility of a compliant intramedullary stem that eliminates over-constraint without generating particulate wear. The compliant stem is built around a compliant mechanism that permits rotation about a single axis. We first established several models to understand the relationship between mechanism geometry and implant performance under a given angular displacement and compressive load. We then used a neural network to identify a design space of geometries that would support an expected 100-year fatigue life inside the body. We additively manufactured one representative mechanism for each of three anatomic locations, and evaluated these prototypes on a KR-210 robot. The neural network predicts maximum stress and torsional stiffness with 2.69% and 4.08% error respectively, relative to finite element analysis data. We identified feasible design spaces for all three of the anatomic locations. Simulated peak stresses for the three stem prototypes were below the fatigue limit. Benchtop performance of all three prototypes was within design specifications. Our results demonstrate the feasibility of designing patient- and joint-specific compliant stems that address the root causes of aseptic loosening. Guided by these results, we expect the use of compliant intramedullary stems in joint reconstruction technology to increase implant lifetime., (© 2024 The Authors.)

Background: In 2005, the Food and Drug Administration placed a black-box warning (the most stringent warning for drugs) on all nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) stating that these agents may cause heart attacks and/or strokes. No level I evidence demonstrates that nonselective NSAIDs increase cardiovascular risk. An alternative hypothesis is that hip and knee osteoarthritis (OA) indirectly causes cardiovascular disease (CVD) through decreased activity and NSAIDs are correlated with CVD as an arthritis treatment., Methods: Systematic reviews were conducted to find observational studies evaluating the association of hip and/or knee OA, CVD, activity, walking, and step counts. The systematic review found studies correlating hip and/or knee OA and CVD morbidity incidence (n = 2); CVD morbidity prevalence (n = 6); odds ratios, relative risks, or hazard ratios of CVD morbidity (n = 11); relative risk, standardized mortality ratios, or hazard ratios of CVD mortality (n = 14); and all-cause mortality hazard ratios associated with NSAID use (n = 3)., Results: Hip OA (5 studies), knee OA (9 studies), and hip and knee OA (6 studies) are linked to an increased risk of CVD morbidity and mortality. Cardiac risk increases with validated disability scores, use of walking aids, walking difficulties, longer follow-up times, younger ages of OA onset, numbers of joints involved, and OA severities. No study linked NSAID use to cardiac disease., Conclusions: All studies with more than 10-year follow-up linked cardiac disease with hip and knee OA. No study linked nonselective NSAID use to CVD. The Food and Drug Administration should reconsider the black-box warnings on naproxen, ibuprofen, and celecoxib., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Most case-control studies compare cancer survivors with general population controls without considering sexual orientation or gender identity. This case-control analysis compared health risk behaviors and health outcomes among sexual and gender minority cancer survivors to those of matched sexual and gender minority participants without cancer (controls)., Methods: Using data from the 2014-2021 Behavioral Risk Factor Surveillance System, a population-based sample of 4507 cancer survivors who self-identified as transgender, gay men, bisexual men, lesbian women, or bisexual women were 1:1 propensity score matched, using age at survey, race and ethnicity, marital status, education, access to health care, and US census region. Within each sexual and gender minority group, behaviors and outcomes were compared between survivors and participants without cancer, and survivors' odds ratios and 95% confidence intervals calculated., Results: Gay male survivors had higher odds of depression, poor mental health, limited usual activities, difficulty concentrating, and fair or poor health. Few differences were observed between bisexual male survivors and participants without cancer. Compared with controls, lesbian female survivors had greater odds of overweight-obese status, depression, poor physical health, and fair or poor health. Bisexual female survivors had the highest rates of current smoking, depression, poor mental health, and difficulty concentrating across all sexual and gender minority groups. Statistically significantly different from transgender controls, transgender survivors had greater odds of heavy alcohol use, physical inactivity, and fair or poor health., Conclusions: This analysis revealed an urgent need to address the high prevalence of engaging in multiple health risk behaviors and not following guidelines to avoid second cancers, additional adverse outcomes, and cancer recurrences among sexual and gender minority cancer survivors., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Inactivation of the retinoblastoma (RB) tumor suppressor in lung adenocarcinoma is associated with the rapid acquisition of metastatic ability and the loss of lung cell lineage commitment. We previously showed that restoration of RB in advanced lung adenocarcinomas in the mouse was correlated with a decreased frequency of lineage decommitted tumors and overt metastases. To identify a causal relationship for RB and its role in reprogramming lineage commitment and reducing metastatic competency in lung adenocarcinoma, we developed multiple tumor spheroid forming lines where RB restoration could be achieved after characterization of the degree of each spheroid's lineage commitment and metastatic ability. Surprisingly, we discovered that RB inactivation dramatically promoted tumor spheroid forming potential in tumors that arise in the KrasLSL-G12D/+; p53flox/flox lung adenocarcinoma model. However, RB reactivation had no effect on the maintenance of tumor spheroid lines once established. In addition, we show that RB-deficient tumor spheroid lines are not uniformly metastatically competent but are equally likely to be nonmetastatic. Interestingly, unlike tumor spheroid maintenance, RB restoration could functionally revert metastatic tumor spheroids to a nonmetastatic cell state. Thus, strategies to reinstate RB pathway activity in lung cancer may reverse metastatic ability and have therapeutic potential. Finally, the acquisition of tumor spheroid forming potential reflects underlying cell state plasticity, which is often predictive of, or even conflated with metastatic ability. Our data support that each is a discrete cell state restricted by RB and question the suitability of tumor spheroid models for their predictive potential of advanced metastatic tumor cell states., Significance: Members of the RB pathway are frequently mutated in lung adenocarcinoma. We show that RB regulates cell state plasticity, tumor spheroid formation, and metastatic competency. Our data indicate that these are independent states where spheroid formation is distinct from metastatic competency. Thus, we caution against conflating spheroid formation and other signs of cell state plasticity with advanced metastatic cell states. Nevertheless, our work supports clinical strategies to reactivate RB pathways., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Introduction: The most common surgical options for geriatric proximal humerus fractures are open reduction and internal fixation (ORIF), hemiarthroplasty (HA), and reverse total shoulder arthroplasty. We used a longitudinal inpatient discharge database to determine the cumulative incidence of conversion to arthroplasty after ORIF of geriatric proximal humerus fractures. The rates of short-term complications and all-cause reoperation were also compared., Patients and Methods: All patients 65 or older who sustained a proximal humerus fracture and underwent either ORIF, HA, or shoulder arthroplasty (SA) as an inpatient from 2000 through 2017 were identified. Survival analysis was performed with ORIF conversion to arthroplasty and all-cause reoperation as the endpoints of interest. Rates of 30-day readmission and short-term complications were compared. Trends in procedure choice and outcomes over the study period were analyzed., Results: A total of 27 102 geriatric patients that underwent inpatient surgical management of proximal humerus fractures were identified. Among geriatric patients undergoing ORIF, the cumulative incidence of conversion to arthroplasty within 10 years was 8.2%. The 10-year cumulative incidence of all-cause reoperation was 12.1% for ORIF patients and less than 4% for both HA and SA patients. Female sex was associated with increased risk of ORIF conversion and younger age was associated with higher all-cause reoperation. ORIF was associated with higher 30-day readmission and short-term complication rates. Over the study period, the proportion of patients treated with ORIF or SA increased while the proportion of patients treated with HA decreased. Short-term complication rates were similar between arthroplasty and ORIF patients in the later cohort (2015-2017)., Conclusion: The 10-year cumulative incidence of conversion to arthroplasty for geriatric patients undergoing proximal humerus ORIF as an inpatient was found to be 8.2%. All-cause reoperations, short-term complications, and 30-day readmissions were all significantly lower among patients undergoing arthroplasty, but the difference in complication rate between arthroplasty and ORIF was attenuated in more recent years. Younger age was a risk factor for reoperation and female sex was associated with increased risk of requiring conversion to arthroplasty after ORIF., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

The p53 tumor suppressor regulates multiple context-dependent tumor suppressive programs. Although p53 is mutated in ~90% of small cell lung cancer (SCLC) tumors, how p53 mediates tumor suppression in this context is unknown. Here, using a mouse model of SCLC in which endogenous p53 expression can be conditionally and temporally regulated, we show that SCLC tumors maintain a requirement for p53 inactivation. However, we identify tumor subtype heterogeneity between SCLC tumors such that p53 reactivation induces senescence in a subset of tumors, while in others, p53 induces necrosis. We pinpoint cyclophilins as critical determinants of a p53-induced transcriptional program that is specific to SCLC tumors and cell lines poised to undergo p53-mediated necrosis. Importantly, inhibition of cyclophilin isomerase activity, or genetic ablation of specific cyclophilin genes, suppresses p53-mediated necrosis by limiting p53 transcriptional output without impacting p53 chromatin binding. Our study demonstrates that intertumoral heterogeneity in SCLC influences the biological response to p53 restoration, describes a cyclophilin-dependent mechanism of p53-regulated cell death, and uncovers putative mechanisms for the treatment of this most-recalcitrant tumor type., (© 2023. The Author(s).)

Community-based conservation can support livelihoods and biodiversity, while reinforcing local and Indigenous values, cultures, and institutions. Its delivery can help address cross-cutting global challenges, such as climate change, conservation, poverty, and food security. Therefore, understanding trends in community-based conservation is pertinent to setting and implementing global goals. We undertook a horizon scan to prioritize 15 emerging threats and opportunities expected to impact the future effectiveness of community-based conservation. Topics relate to global biodiversity policy; human rights; shifting human geography; inclusion, diversity, equity, and access; conservation finance and income; and economic reforms. Our findings offer guidance on strengthening community-based conservation to achieve global environmental and development goals., Competing Interests: Declaration of interests None declared by authors., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The purpose of this study is to describe the context, curriculum design, and pilot evaluation of the educational program "Sexual and Gender Minority Cancer Curricular Advances for Research and Education" (SGM Cancer CARE), a workshop for early-career researchers and healthcare providers interested in gaining knowledge and skills in sexual and gender minority (SGM) cancer research and healthcare advocacy. A needs assessment of a sample of clinicians and researchers (n = 104) and feedback from an Advisory Board informed the curriculum design of the SGM Cancer CARE workshop. Four SGM-tailored modules, focusing on epidemiology, clinical research, behavioral science and interventions, and community-based participatory approaches, were developed and tested in a 2.5-day virtual format among 19 clinicians and researchers. A fifth module to provide feedback to participants on brief presentations about their SGM cancer research ideas or related efforts was added later. A mixed-methods evaluation comprised of pre- and post-modular online evaluation surveys and virtual focus groups was used to determine the degree to which the workshop curriculum met participant needs. Compared to pre-module evaluations, participants reported a marked increase in SGM cancer research knowledge in post-module scores. Quantitative results were supported by our qualitative findings. In open field response survey questions and post-workshop focus groups, participants reported being extremely pleased with the content and delivery format of the SGM Cancer CARE workshop. Participants did regret not having the opportunity to connect with instructors, mentors, and colleagues in person. The SGM Cancer CARE curriculum was shown to increase the knowledge, skills, and level of preparedness of early-career clinicians and scientists to conduct culturally relevant and appropriate research needed to improve care for SGM persons across the cancer care continuum from prevention to survivorship., (© 2022. The Author(s) under exclusive licence to American Association for Cancer Education.)

Objective: Our primary objectives were to (1) determine the rate of requiring conversion to arthroplasty after open reduction internal fixation (ORIF) of geriatric distal femur fractures and (2) compare 10-year reoperation rates after ORIF versus primary arthroplasty for geriatric distal femur fractures., Design: Propensity-matched retrospective cohort study., Setting: All centers participating in the California Office of Statewide Health Planning and Development (OSHPD) database., Patients/participants: All patients 65 years of age or older who underwent operative management of a distal femur fracture between 2000 and 2017., Intervention: ORIF, total knee arthroplasty (TKA), or distal femur replacement (DFR)., Main Outcome Measurements: Reoperation., Results: A total of 16,784 patients with geriatric distal femur fracture were identified, of which 16,343 (97.4%) underwent ORIF. The cumulative incidence of conversion to arthroplasty within 10 years of ORIF was found to be 3.5%, with young age and female sex identified as risk factors for conversion. There was no significant difference in 10-year reoperation-free survival rate between propensity-matched patients undergoing ORIF versus primary arthroplasty (94.5% vs. 96.2%, P = 0.659). There were no differences in short-term complication or readmission rates between matched treatment cohorts, but arthroplasty was associated with a higher rate of wound infection within 90 days (2.0% vs. 0.2%, P = 0.011)., Conclusions: The 10-year cumulative incidence of conversion to arthroplasty after ORIF was found to be low. There was no significant difference in long-term reoperation-free survival rates between patients undergoing ORIF versus primary arthroplasty. Primary arthroplasty was associated with significantly higher rates of acute wound or joint infection., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no financial disclosures or conflicts of interest related to the current work., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Alemtuzumab is effective in reducing relapse rate and disability, but limited data exist on its effect on cognitive function in relapsing multiple sclerosis (RMS). The present study assessed neurocognitive function and safety associated with alemtuzumab treatment in RMS., Methods: This longitudinal, single-arm, prospective study included people with RMS (aged 25-55 years) who were treated with alemtuzumab in clinical practice in the United States of America and Canada. The first participant was enrolled in December 2016. The primary endpoint was the change from baseline to post-baseline (month [M] 12/24) in MS-COGnitive (MS-COG) composite score. Secondary endpoints included Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT-R), Selective Reminding Test (SRT), Controlled Oral Word Association Test (COWAT), and Automated Neuropsychological Assessment Metrics (ANAM) scores. Depression and fatigue were assessed using Hamilton Rating Scale-Depression (HAM-D) and Fatigue Severity Scale (FSS)/Modified Fatigue Impact Scale (MFIS), respectively. Magnetic resonance imaging (MRI) parameters were assessed when available. Safety was assessed throughout the study. Descriptive statistics were used for the pre-specified statistical analyses. Since the study was terminated early (November 2019) because of operational and resource difficulties, post hoc analyses for statistical inference were performed among participants who had a baseline value and at least one complete post-baseline assessment for cognitive parameters, fatigue, or depression., Results: Of the 112 participants enrolled, 39 were considered as the primary analysis population at M12. At M12, a mean change of 0.25 (95% confidence interval [CI]: 0.04, 0.45; p = 0.0049; effect size [ES]: 0.39) was observed in the MS-COG composite score. Improvements were observed in processing speed (based on PASAT and SDMT; p < 0.0001; ES: 0.62), as well as in individual PASAT, SDMT and COWAT scores. An improvement was also noted in HAM-D (p = 0.0054; ES: -0.44), but not in fatigue scores. Among MRI parameters, decreases in burden of disease volume (BDV; ES: -0.12), new gadolinium-enhancing lesions (ES: -0.41) and newly active lesions (ES: -0.07) were observed at M12. About 92% of participants showed stable or improved cognitive status at M12. There were no new safety signals reported in the study. The most common adverse events (≥10% of participants) were headache, fatigue, nausea, insomnia, urinary tract infection, pain in extremity, chest discomfort, anxiety, dizziness, arthralgia, flushing, and rash. Hypothyroidism (3.7%) was the most frequent adverse event of special interest., Conclusion: The findings from this study suggest that alemtuzumab has a positive impact on cognitive function with significant improvements in processing speed and depression in people with RMS over a period of 12 months. The safety profile of alemtuzumab was consistent with previous studies., Competing Interests: Declaration of Competing Interest This study was funded by Sanofi. Jeffrey Wilken received grants from Biogen; grants and personal fees from Sanofi; consulting fees from Bristol Myers Squibb (BMS); and speaker fees from Biogen, Sanofi, and Serono. Anthony Traboulsee is the MS Society of Canada Research Chair at the University of British Columbia (UBC) supported by the MS/MRI Research Group and received research funding from the MS Society of Canada, Roche, and Sanofi; and also received honoraria or travel support from Consortium of MS Centers, Roche, Sanofi. Flavia Nelson is funded by National Institutes of Health (NIH), the University of Minnesota Institute for translational Neuroscience and is an advisor for Sanofi, Genentech, BMS, Horizon and Novartis. Carolina Ionete reported receiving compensation for advisory board participation for Sanofi, and research support from NIH, National Multiple Sclerosis Society (NMSS), Department of Defense (DOD), Consortium of MS Centers, Dan and Diane Riccio Foundation, Biogen, Roche, and Novartis. Shannon Kolind received research support from Roche, Genzyme, the MS Society of Canada, the Natural Sciences and Engineering Research Council (NSERC), Vancouver Coastal Health Research Institute (VCHRI), Michael Smith Foundation for Health Research (MSFHR), the Canadian Institutes of Health Research (CIHR), Brain Canada, and Milan & Maureen Ilich Foundation, and consulting fees from Novartis. Timothy Fratto has nothing to disclose. Robert Kane has been a consultant for Biogen Idec. Roopali Gandhi, Andreea M. Rawlings, and Nora Roesch are employees of Sanofi and may hold stock and/or stock options in the company. Mark A. Ozog was an employee of Sanofi and may hold stock and/or stock options in the company (at the time of study). John DeLuca reported personal compensation for consulting from Celgene/BMS, Biogen Idec, Novartis, Consortium of MS Centers, and MedRhythms; is a speaker for Sanofi, Biogen IDEC and Excemed; received grant funding from Biogen Idec, EMD Serono, Canadian MS Society, NIH, National Multiple Sclerosis Society, and Consortium of MS Centers., (Copyright © 2023. Published by Elsevier B.V.)

Background: In many resource-constrained countries, control of blood pressure (BP) is low. Antihypertensive drug prescribing practices may influence BP control. However, adherence of prescribing to treatment guidelines may not be optimal in resource-constrained settings. The aim of this study was to evaluate the pattern of blood pressure-lowering medication prescribing, and how it adheres to treatment guidelines, and to identify the relationship between medication prescriptions and BP control., Methods: It was a cross-sectional study of hypertensive outpatients at the Korle Bu Teaching Hospital (KBTH) Family Medicine department (FMD)/Polyclinic. Data was collected with a validated structured form. Adherence of "prescribing" to recommendations of the 2017 Standard Treatment Guidelines of Ghana and 2018 European Society of Cardiology guidelines was assessed using a composite measure. We analyzed data with SPSS., Results: About 81% (247/304) of patients received two or more antihypertensive drugs. Most patients (41%; 267/651) received calcium channel blockers (CCB), and 21.8% (142/651), 15.7% (102/651) and 12.7% (83/651) were on diuretics, angiotensin-receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors respectively. CCB plus RAS inhibitor (50%) was the most prescribed two-drug combination. Number of BP drugs per patient had a statistically significant inverse relationship with BP control (beta Coefficient = -0.402; 95% Cl: 1.252-2.470; p  = 0.015). The composite adherence score was 0.73 (moderate adherence) but Single-pill combination (SPC) was poor (3.2%; n  = 8)., Conclusion: Most patients received multiple-pill combination treatment, and overall adherence to guidelines was suboptimal, largely owing to complex drug therapy. Number of drugs predicted BP control. Our findings suggest a need to prioritize simplified treatment, and implement other strategies to improve hypertension guideline adherence. Further research on the influence of SPC on BP control may inform future hypertension guidelines in Ghana and elsewhere in Africa., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Study Design: A retrospective, case-control study., Objective: We aim to build a risk calculator predicting major perioperative complications after anterior cervical fusion. In addition, we aim to externally validate this calculator with an institutional cohort of patients who underwent anterior cervical discectomy and fusion (ACDF)., Summary of Background Data: The average age and proportion of patients with at least one comorbidity undergoing ACDF have increased in recent years. Given the increased morbidity and cost associated with perioperative complications and unplanned readmission, accurate risk stratification of patients undergoing ACDF is of great clinical utility., Methods: This is a retrospective cohort study of adults who underwent anterior cervical fusion at any nonfederal California hospital between 2015 and 2017. The primary outcome was major perioperative complication or 30-day readmission. We built standard and ensemble machine learning models for risk prediction, assessing discrimination, and calibration. The best-performing model was validated on an external cohort comprised of consecutive adult patients who underwent ACDF at our institution between 2013 and 2020., Results: A total of 23,184 patients were included in this study; there were 1886 cases of major complication or readmissions. The ensemble model was well calibrated and demonstrated an area under the receiver operating characteristic curve of 0.728. The variables most important for the ensemble model include male sex, medical comorbidities, history of complications, and teaching hospital status. The ensemble model was evaluated on the validation cohort (n=260) with an area under the receiver operating characteristic curve of 0.802. The ensemble algorithm was used to build a web-based risk calculator., Conclusion: We report derivation and external validation of an ensemble algorithm for prediction of major perioperative complications and 30-day readmission after anterior cervical fusion. This model has excellent discrimination and is well calibrated when tested on a contemporaneous external cohort of ACDF cases., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Lesbian, gay, bisexual, transgender, and queer (LGBTQ+) adults experience a wide variety of unique challenges accessing healthcare. These barriers may be exacerbated among older LGBTQ+ people due to intersecting, marginalized identities. To prepare physicians to address the healthcare needs of older LGBTQ+ adults, graduate medical education (GME) must include training about the specific needs of this population. Prior studies demonstrate a lack of LGBTQ+ training in GME curricula. Here, we investigated the presence of LGBTQ+ curricula in internal medicine residencies and geriatrics fellowships through a national survey. Over 62.0% of internal medicine (n = 49) and 65.6% (n = 21) of geriatric medicine fellowship program directors, responding to the survey, reported content relevant to the health of older LGBTQ+ adults. Education about LGBTQ+ health in internal medicine residencies and geriatrics fellowships is vital for the provision of culturally-competent healthcare and to create an inclusive environment for older LGBTQ+ patients., Competing Interests: MCM has support from the National Institute of Mental Health under Award F30MH118762. The authors report there are no competing interests to declare.

Purpose: Family-centered rehabilitative care optimizes outcomes for children with significant developmental disabilities. Family-centered services involve assessing family resources that promote positive developmental outcomes for children. Little is known regarding family resources in the context of caring for a child with developmental disabilities in Brazil due to an absence of validated measures. This study describes the translation and cultural adaptation of the Family Resource Scale and explored the measurement quality of the resulting measure (the Brazilian-Family Resource Scale, or B-FRS)., Methods: A rigorous serial translation process that emphasized linguistic accuracy as well as cultural adaptation was utilized. The resulting 27-item B-FRS was theoretically related and reflected the contextual intent of the original measure., Results: A four-factor scoring approach yielded acceptable internal consistency estimates for the subscales and total scale score. Overall, low levels of family resources were reported by caregivers of children with Congenital Zika Syndrome. Low family resources were associated with parental depressive and stress-related symptoms., Conclusion: Confirmatory factor analysis of the B-FRS in a larger sample is recommended. Practitioners in Brazil should broadly consider family needs and resources to provide family-centered care that is effective for the child and engages the family in a way that highlights their strengths and promotes positive developmental trajectories.

Background: Our daily intake of food provides nutrients for the maintenance of health, growth, and development. The field of nutrigenomics aims to link dietary intake/nutrients to changes in epigenetic status and gene expression., Summary: Although the relationship between our diet and our genes in under intense investigation, there is still a significant aspect of our genome that has received little attention with regard to this. In the past 15 years, the importance of genome organization has become increasingly evident, with research identifying small-scale local changes to large segments of the genome dynamically repositioning within the nucleus in response to/or mediating change in gene expression. The discovery of these dynamic processes and organization maybe as significant as dynamic plate tectonics is to geology, there is little information tying genome organization to specific nutrients or dietary intake., Key Messages: Here, we detail key principles of genome organization and structure, with emphasis on genome folding and organization, and link how these contribute to our future understand of nutrigenomics., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

The Supreme Court's 2020 ruling prohibiting workplace discrimination based on sexual orientation or gender identity ( Bostock v Clayton County ) offers new legal protections for LGBTQ+ employees and allies and new opportunities for academic medicine to advance LGBTQ+ inclusion at their institutions. In this perspective piece, the authors examine the history of LGBTQ+ community recognition, tolerance, protections, and ongoing inclusion and the advocacy efforts led by LGBTQ+ patients, community activists, and medical colleagues. They also examine the current limitations of the court's ruling and recommend future actions to advance workplace and health equity. While recent advancements in equality have not erased chronic barriers to inclusion and advancement, they can pave the way for leaders in research, education, and clinical care to shape national health guidelines and policies that impact the health of all Americans., (Copyright © 2022 by the Association of American Medical Colleges.)

Over the last decades, increased emission of greenhouse gases has led to hot weather extremes, heavy precipitation and worsening of agricultural and ecological droughts. Although Africa's contribution to climate change is minimal, the continent is especially vulnerable to its effects. This report aims to describe the effect of climate change leading to drought in Kilifi County, Kenya, and the communities' experiences of this effect on food availability. During their community rotation, residents from a university in Nairobi, Kenya, evaluated changes in weather patterns and nutrition indicators in Kilifi County and conducted focus group discussions (FGDs) with community members and health care stakeholders to explore challenges in access to adequate nutrition and possible local solutions. Kilifi County has one of the highest rates of undernutrition in Kenya, with one in five under-5 children being underweight. County data showed that rainfall in the last 4 years has become increasingly unpredictable, resulting in reduced household milk production, one of the indicators of nutrition security. Three major themes emerged from the FGDs: lack of food variety, collapse of drought mitigating projects and increasing poverty levels. Possible solutions to these problems include promoting alternatives to the current diet that are culturally sensitive and adaptable to recent climate changes, ensuring continuity of agricultural and financial support projects and improved local leadership and governance.

Background: C5 palsy is a common postoperative complication after cervical fusion and is associated with increased health care costs and diminished quality of life. Accurate prediction of C5 palsy may allow for appropriate preoperative counseling and risk stratification. We primarily aim to develop an algorithm for the prediction of C5 palsy after instrumented cervical fusion and identify novel features for risk prediction. Additionally, we aim to build a risk calculator to provide the risk of C5 palsy., Methods: We identified adult patients who underwent instrumented cervical fusion at a tertiary care medical center between 2013 and 2020. The primary outcome was postoperative C5 palsy. We developed ensemble machine learning, standard machine learning, and logistic regression models predicting the risk of C5 palsy-assessing discrimination and calibration. Additionally, a web-based risk calculator was built with the best-performing model., Results: A total of 1024 patients were included, with 52 cases of C5 palsy. The ensemble model was well-calibrated and demonstrated excellent discrimination with an area under the receiver-operating characteristic curve of 0.773. The following features were the most important for ensemble model performance: diabetes mellitus, bipolar disorder, C5 or C4 level, surgical approach, preoperative non-motor neurologic symptoms, degenerative disease, number of fused levels, and age., Conclusions: We report a risk calculator that generates patient-specific C5 palsy risk after instrumented cervical fusion. Individualized risk prediction for patients may facilitate improved preoperative patient counseling and risk stratification as well as potential intraoperative mitigating measures. This tool may also aid in addressing potentially modifiable risk factors such as diabetes and obesity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Abstract: Electroconvulsive therapy (ECT) is a highly therapeutic and cost-effective treatment for severe and/or treatment-resistant major depression. However, because of the varied clinical practices, there is a great deal of heterogeneity in how ECT is delivered and documented. This represents both an opportunity to study how differences in implementation influence clinical outcomes and a challenge for carrying out coordinated quality improvement and research efforts across multiple ECT centers. The National Network of Depression Centers, a consortium of 26+ US academic medical centers of excellence providing care for patients with mood disorders, formed a task group with the goals of promoting best clinical practices for the delivery of ECT and to facilitate large-scale, multisite quality improvement and research to advance more effective and safe use of this treatment modality. The National Network of Depression Centers Task Group on ECT set out to define best practices for harmonizing the clinical documentation of ECT across treatment centers to promote clinical interoperability and facilitate a nationwide collaboration that would enable multisite quality improvement and longitudinal research in real-world settings. This article reports on the work of this effort. It focuses on the use of ECT for major depressive disorder, which accounts for the majority of ECT referrals in most countries. However, most of the recommendations on clinical documentation proposed herein will be applicable to the use of ECT for any of its indications., Competing Interests: D.F.M. has received research support for the clinical study of ketamine in depression and past travel expenses for program and research development from the National Network of Depression Centers. He has research support from Janssen at present. He has past research funding from Neuronetics and St. Jude Medical in the past 10 years; Mustafa Husain has received support from the National Institutes of Health (NIH), National Institute of Mental Health (NIMH), National Institute on Aging (NIA), National Institute of Neurological Disorders and Stroke, Brain Initiative, and the Stanley Medical Research Institute. He has received industry grant support from Abbott, Cyberonics, Neuronetics, Brainsway, and NeoSync; William M. McDonald is a member of the American Psychiatric Association Council on Research representing electroconvulsive therapy and neuromodulation therapies. He is compensated as the chair of the Data Safety and Monitoring Board (DSBM) for an NIA multicenter study. He is on the Board of Skyland Trail and 3Keys. He is a paid consultant for Signant Health. He has received past funding from the Stanley Foundation, Soterix, Neuronetics, NeoSync, and Cervel Neurotherapeutics. He has an endowed chair funded by the JB Fuqua Foundation. S. Selek received internal funding from the University of Texas Health Science Center at Houston McGovern Medical School, Louis A. Faillace Department of Psychiatry. S.M.M. has received research funding from the NIH and is a consultant for the Pearson Assessment. E.A. has received funding from the NIA. J.H.W. is a consultant or has equity interest at Mindstreet Inc; American Psychiatric Publishing, Inc; Guilford Press; and Simon and Schuster Book Royalties. He has received grant support from the Agency for Healthcare Research and Quality. T.S. has received funding from the NIH and the Foundation of Hope for Research and Treatment of Mental Illness. W.I. has received funding from the NIMH T32 Psychiatric Epidemiology Training Program (T32MH014592-41). I.M.R. was supported by the NIMH (R01 MH121542) and The Jager Family Foundation. P.P.Z., M.M., R.W.S., S.K.C., K.R., B.R.C., S.J.S., P.D.P., R.D.W., N.F.R., M.T.B., M.C., K.G., A.F., N.T.T., O.F.P., M.J.D., K.K., S. Sampson, and Y.S. have no conflicts of interest or financial disclosures to report., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Notwithstanding the availability of effective treatments, asymptomatic nature and the interminable treatment length, adherence to medication remains a substantial challenge among patients with hypertension. Suboptimal adherence to BP-lowering agents is a growing global concern that is associated with the substantial worsening of disease, increased service utilization and health-care cost escalation. This study aimed to explore medication adherence and its associated factors among hypertension outpatients attending a tertiary-level cardiovascular hospital in Tanzania., Methods: The pill count adherence ratio (PCAR) was used to compute adherence rate. In descriptive analyses, adherence was dichotomized and consumption of less than 80% of the prescribed medications was used to denote poor adherence. Logistic regression analyses was used to determine factors associated with adherence., Results: A total of 849 outpatients taking antihypertensive drugs for ≥1 month prior to recruitment were randomly enrolled in this study. The mean age was 59.9 years and about two-thirds were females. Overall, a total of 653 (76.9%) participants had good adherence and 367 (43.2%) had their blood pressure controlled. Multivariate logistic regression analysis showed; lack of a health insurance (OR 0.5, 95% CI 0.3-0.7, p<0.01), last BP measurement >1 week (OR 0.6, 95% CI 0.4-0.8, p<0.01), last clinic attendance >1 month (OR 0.4, 95% CI 0.3-0.6, p<0.001), frequent unavailability of drugs (OR 0.6, 95% CI 0.3-0.9, p = 0.03), running out of medication before the next appointment (OR 0.6, 95% CI 0.4-0.9, p = 0.01) and stopping medications when asymptomatic (OR 0.6, 95% CI 0.4-0.8, p<0.001) to be independent associated factors for poor adherence., Conclusion: A substantial proportion of hypertensive outpatients in this tertiary-level setting had good medication adherence. Nonetheless, observed suboptimal blood pressure control regardless of a fairly satisfactory adherence rate suggests that lifestyle modification plays a central role in hypertension management., Competing Interests: The authors declare that they have no conflicts of interest in relation to this work., (© 2022 Pallangyo et al.)

Purpose: Posterior cervical fusion is associated with increased rates of complications and readmission when compared to anterior fusion. Machine learning (ML) models for risk stratification of patients undergoing posterior cervical fusion remain limited. We aim to develop a novel ensemble ML algorithm for prediction of major perioperative complications and readmission after posterior cervical fusion and identify factors important to model performance., Methods: This is a retrospective cohort study of adults who underwent posterior cervical fusion at non-federal California hospitals between 2015 and 2017. The primary outcome was readmission or major complication. We developed an ensemble model predicting complication risk using an automated ML framework. We compared performance with standard ML models and logistic regression (LR), ranking contribution of included variables to model performance., Results: Of the included 6822 patients, 18.8% suffered a major complication or readmission. The ensemble model demonstrated slightly superior predictive performance compared to LR and standard ML models. The most important features to performance include sex, malignancy, pneumonia, stroke, and teaching hospital status. Seven of the ten most important features for the ensemble model were markedly less important for LR., Conclusion: We report an ensemble ML model for prediction of major complications and readmission after posterior cervical fusion with a modest risk prediction advantage compared to LR and benchmark ML models. Notably, the features most important to the ensemble are markedly different from those for LR, suggesting that advanced ML methods may identify novel prognostic factors for adverse outcomes after posterior cervical fusion., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cardiovascular disease (CVD) is the biggest cause of death globally. CVD is caused by atherosclerosis which is the accumulation of fatty deposits, often within the fine arteries of the heart or brain. These blockages reduce blood flow and lead to oxygen starvation (ischemia) which can lead to heart attacks and strokes. To treat blocked arteries an implantable device called a stent re-opens the artery to reinstate blood flow to the organ. The stent itself can become blocked over time by cell growth (intimal hyperplasia) which is characterised by excessive smooth muscle cell proliferation. Sensors based on electrical impedance spectroscopy (EIS) embedded in a stent could detect this re-blocking to allow for early intervention. Using platinum interdigitated electrodes on silicon sensor wafers we were able to co-culture different ratios of mouse smooth muscle cells and mouse endothelial cells on these sensors. This mimics the complex, multicellular environment which a stent is found in vivo when undergoing neo-intimal hyperplasia. Trends in the cell impedances were then characterised using the detection frequency and the gradient of change between populations over time which we termed 'Peak Cumulative Gradients (PCG). PCGs were calculated to successfully discriminate each cell type. This work moves towards a sensor that may help guide clinician's decision-making in a disease that is historically silent and difficult to detect. Clinical Relevance-This moves towards an early warning system for the detection of neo intimal hyperplasia ultimately leading to a reduction in stent complications.

Purpose: Facial trauma and orbital fractures are common reasons for ophthalmology consultation in the emergency department (ED). The purpose of this study is to assess intervention rates and evaluate the acuity of ophthalmology consultation for orbital fractures in the ED., Basic Procedures: A retrospective chart review of orbital fractures was conducted over a 23-month period. 379 cases of orbital fractures were identified in a single-center study. All patients that received an ophthalmology consultation in the ED were included. Demographics, mechanism and location of orbital fracture, ophthalmic complications, and surgical and non-surgical ophthalmic interventions were recorded. The primary study outcome was the rate of ophthalmic consultation and intervention with and without retrospective application of our proposed South Texas Orbital Fracture Protocol (STOP)., Results: Immediate ophthalmic intervention was performed in 18.7% of patients. Statistically significant subjective, radiographic, and physical exam features correlating with ophthalmic intervention were identified and included globe rupture, concern for entrapment, orbital roof fractures, and retrobulbar hematoma. Retrospective application of our proposed South Texas Orbital Fracture Protocol (STOP) would have resulted in 186 of 379 patients requiring ophthalmology consultation, thus reducing consultation rate by 51% with an improved rate of intervention from 18.7% to 37.6%., Conclusions: Orbital fractures can be associated with severe ocular complications. Most cases, however, do not require emergent evaluation by an ophthalmologist. We propose the South Texas Orbital Fracture Protocol (STOP) for proper assessment and triaging of orbital fractures in the ED. While this clinical decision-making tool requires validation, it may offer improved healthcare efficiency, reduced costs, fewer unnecessary inter-facility transfers, and less burnout for ophthalmology residents., Competing Interests: Declaration of Competing Interest There were no relevant financial conflicts of interest regarding this work. There was no funding received for this study., (Published by Elsevier Inc.)

Objective: Although proximal neck dilatation following infrarenal endovascular aneurysm repair (EVAR) is common and is associated with proximal graft failure, little is known about sealing zone dilatation and its clinical relevance following fenestrated EVAR (FEVAR). We studied proximal seal dilatation (PSD) dynamics following FEVAR and assessed its clinical significance., Methods: We included all consecutive patients treated for a juxta-/supra-renal aneurysm with fenestrated EVAR using the Zenith Fenestrated Endovascular Graft (Cook Medical, Bloomington, Ind) from 2008 to 2018 in two large teaching hospitals in the Netherlands. The primary outcome was PSD over time and was determined using a linear mixed-effects model. Secondary outcomes included associations for early PSD and difference in aortic dilatation at the level of the covered stent compared with the bare stent. Proximal seal-related adverse events were also obtained., Results: Our cohort included 84 patients with a median computed tomography angiography follow-up time of 24.5 months (interquartile range [IQR], 17-42 months). Maximum aneurysm diameter was 60.1 mm (IQR, 56.9-67.2 mm). Mean proximal seal diameter at baseline was 26.2 mm (standard deviation [SD], ±2.8 mm), mean stent oversizing was 20.1% (SD, ±9.1%), and mean proximal seal length was 29.5 mm (SD, ±11.7 mm). Proximal seal dilatation of 1.7 mm (95% confidence interval [CI], 1.4-2.1 mm) was found in the first year, decelerating thereafter (second year, 0.9 mm/year; 95% CI, 0.7-1.1 mm/y). Over 10% PSD at 1 year occurred in 22 patients (27%) and was associated with stent graft oversizing (odds ratio, 1.1; 95% CI, 1.03-1.2; P = .008) and a lower number of target vessels (four fenestrations/ref two fenestrations: odds ratio, 0.13; 95% CI, 0.02-0.74; P = .029). At last available imaging, dilatation difference was higher at the level of the covered stent compared with the bare stent (3.0 mm [IQR, 1.3-5.1 mm] vs 1.6 mm [IQR, 0.8-2.5 mm]; P < .001). During the study period, only one patient (1.2%) developed a proximal seal-related adverse event (type IA endoleak)., Conclusions: PSD is present following FEVAR, occurring at a faster rate in the first year and subsequently decelerating thereafter, similarly to neck dilatation after standard infrarenal EVAR. Although its clinical implication seems to remain limited in the first years following implantation, further research is required to assess the effect of PSD on long-term FEVAR outcomes., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The demand and incidence of anatomic total shoulder arthroplasty (aTSA) procedures is projected to increase substantially over the next decade. There is a paucity of accurate risk prediction models which would be of great utility in minimizing morbidity and costs associated with major post-operative complications. Machine learning is a powerful predictive modeling tool and has become increasingly popular, especially in orthopedics. We aimed to build a ML model for prediction of major complications and readmission following primary aTSA., Methods: A large California administrative database was retrospectively reviewed for all adults undergoing primary aTSA between 2015 to 2017. The primary outcome was any major complication or readmission following aTSA. A wide scope of standard ML benchmarks, including Logistic regression (LR), XGBoost, Gradient boosting, AdaBoost and Random Forest were employed to determine their power to predict outcomes. Additionally, important patient features to the prediction models were indentified., Results: There were a total of 10,302 aTSAs with 598 (5.8%) having at least one major post-operative complication or readmission. XGBoost had the highest discriminative power (area under receiver operating curve AUROC of 0.689) of the 5 ML benchmarks with an area under precision recall curve AURPC of 0.207. History of implant complication, severe chronic kidney disease, teaching hospital status, coronary artery disease and male sex were the most important features for the performance of XGBoost. In addition, XGBoost identified teaching hospital status and male sex as markedly more important predictors of outcomes compared to LR models., Conclusion: We report a well calibrated XGBoost ML algorithm for predicting major complications and 30-day readmission following aTSA. History of prior implant complication was the most important patient feature for XGBoost performance, a novel patient feature that surgeons should consider when counseling patients., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Complex facial lacerations are frequently encountered in the combat environment. Trauma with soft-tissue loss of the periorbital region offers particular challenges in terms of operative reconstruction. Cicatricial changes in the sub-acute phase can lead to eyelid malposition and lagophthalmos. The authors present a novel technique for acute reconstruction of periorbital trauma with eyelid soft-tissue loss with simultaneous full-thickness skin grafting and amniotic membrane grafting. The technique involves standard preparation of the surgical area of injury and infiltration with local anesthetic. Initially, the area of injury is copiously irrigated, and debridement of any necrotic tissue is accomplished. Amniotic membrane grafting is then performed over the defect. Approximately 2 mm × 2 mm full-thickness skin grafts are procured and distributed over the initial amniotic membrane graft. A second amniotic membrane graft is then secured over the skin graft-amniotic membrane graft complex with cyanoacrylate tissue adhesive. A bolstered suture tarsorrhaphy is performed to minimize tissue trauma during the healing process. The operative and postsurgical outcomes were assessed. The graft site healed well without cicatricial changes or lagophthalmos. Peripheral small papillomatous lesions did develop requiring excision for cosmesis, but ultimately the graft site demonstrated appropriate coverage and healthy re-epithelialization over the previous defect. This case demonstrates the viability of simultaneous full-thickness skin grafting with concomitant amniotic membrane grafting for the acute reconstruction of periorbital trauma with eyelid anterior lamella tissue loss. An excellent cosmetic and functional outcome was attained. By providing acute reconstruction, the risk of damage secondary to cicatricial periorbital changes may be avoided., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

An adequate daily intake of minerals is essential for the prevention of chronic nutrition-related and degenerative diseases, including cancer, cardiovascular disease, and obesity. Seaweeds are marine aquatic vegetable that are rich in nutrients. They also have a natural and sustainable origin and clean and renewable sources when they come from marine aquaculture or controlled fisheries. Seaweeds have high nutritional value as a source of polyunsaturated fatty acids, proteins, carbohydrates, vitamins, and especially minerals. They are known for their high mineral content, which is gathered from seawater depending on the seasonal variation and the environment. Seaweeds are consequently rich in macro-elements and trace elements, with a mineral content at least 10 times higher than terrestrial plants and reaching 20-50% of its dry weight. Therefore, seaweeds can make an important contribution to the daily intake of minerals and are a promising source of essential minerals for functional food, food supplements, and nutraceuticals. The aim of the present review is to compare the contents of essential minerals (K, Ca, Na, P, Cu, Fe, Se, Mn, Zn, Mg, Cr, and I) as well as potential toxic minerals (Hg, Pb, Cd, As, and Al) in 14 main edible seaweeds that have availability of biomass from harvest and aquaculture. Another goal is to establish their safety in foods and contributions to the Recommended Dietary Allowance (RDA) and adequate intake (AI) values.

Introduction: Previous research has shown that patients from historically marginalized groups in the United States tend to have poorer outcomes after joint replacement surgery and that they are less likely to receive joint replacement surgery at high-volume hospitals. However, little is known regarding how this group of patients chooses their joint replacement surgeon. The purpose of this study was to understand the factors influencing the choice of joint replacement surgeon amongst a diverse group of patients., Methods: Semi-structured interviews were conducted with Medicare patients who underwent a hip or knee replacement within the last 24 months (N = 38) at an academic and community hospital. Interviews were audio recorded, transcribed and verified for accuracy. Transcripts were reviewed using iterative content analysis to extract key themes related to how respondents chose their joint replacement surgeon., Results and Discussion: MD referral/recommendation appears to be the strongest factor influencing joint replacement surgeon choice. Other key considerations are hospital reputation and surgeon attributes-including operative experience, communication skills, and participation in shared decision-making. Gender/ethnicity of a surgeon, industry payments to surgeons, number of publications and cost did not play a large role in surgeon choice., Conclusion and Clinical Relevance: The process of choosing a joint replacement surgeon is a complex decision-making process with several factors at play. Despite growing availability of information regarding surgeons, patients largely relied on referrals for choosing their joint replacement surgeon regardless of ethnicity. Referring physicians need to ensure that patients are able to access hospital and surgeon outcomes, operative volume, and industry-payment information to learn more about their orthopedic surgeons in order to make an informed choice., Competing Interests: Declaration of Competing Interest Dr. Buerba reports grants from J. Robert Gladden Society (JRGOS) during the conduct of the study. All other authors have nothing to disclose., (Copyright © 2021 National Medical Association. Published by Elsevier Inc. All rights reserved.)