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ABSTRACTHeterochromatin is an organizational property of eukaryotic chromosomes, characterized by extensive DNA and histone modifications, that is associated with the silencing of transposable elements and repetitive sequences. Maintaining heterochromatin is crucial for ensuring genomic integrity and stability during the cell cycle. During meiosis, heterochromatin is important for homologous chromosome synapsis, recombination, and segregation, but our understanding of meiotic heterochromatin formation and condensation is limited. In this review, we focus on the dynamics and features of heterochromatin and how it condenses during meiosis in plants. We also discuss how meiotic heterochromatin influences the interaction and recombination of homologous chromosomes during prophase I.

Vertebral compression fractures (VCF) from trauma, osteoporosis, or pathologic reasons are a significant cause of severe pain and decreased functionality, both of which pose a considerable functional and financial burden to the patient.

Introduction: While emergency department (ED) crowding has deleterious effects on patient care outcomes and operational efficiency, impacts on the experience for patients discharged from the ED are unknown. We aimed to study how patient-reported experience is affected by ED crowding to characterize which factors most impact discharged patient experience. Methods: This institutional review board-exempt, retrospective, cohort study included all discharged adult ED patients July 1, 2020–June 30, 2021 with at least some response data to the the National Research Corporation Health survey, sent to most patients discharged from our large, academic medical center ED. Our query yielded 9,401 unique encounters for 9,221 patients. Based on responses to the summary question of whether the patient was likely to recommend our ED, patients were categorized as “detractors” (scores 0-6) or “non-detractors” (scores 7-10). We assessed the relationship between census and patient experience by 1) computing percentage of detractors within each care area and assessing for differences in census and boarder burden between detractors and non-detractors, and 2) multivariable logistic regression assessing the relationship between likelihood of being a detractor in terms of the ED census and the patient’s last ED care area. A second logistic regression controlled for additional patient- and encounter-specific covariates.  Results: Survey response rate was 24.8%. Overall, 13.9% of responders were detractors. There was a significant difference in the average overall ED census for detractors (average 3.70 more patients physically present at the time of arrival, 95% CI 2.33- 5.07). In unadjusted multivariable analyses, three lower acuity ED care areas showed statistically significant differences of detractor likelihood with changes in patient census. The overall area under the curve (AUC) for the unadjusted model was 0.594 (CI 0.577-0.610). The adjusted model had higher AUC (0.673, CI 0.657- 0.690]; P

Alcohol use disorder (AUD) is a complex and widespread disease with limited pharmacotherapies. Preclinical animal models of AUD use a variety of voluntary alcohol consumption procedures to recapitulate different phases of AUD, including binge alcohol consumption and dependence. However, voluntary alcohol consumption in mice is widely variable, making it difficult to reproduce results across labs. Accumulating evidence indicates that different brands of commercially available rodent chow can profoundly influence alcohol intake. In this study, we investigated the effects of three commercially available and widely used rodent diet formulations on alcohol consumption and preference in C57BL/6 J mice using the 24 h intermittent access procedure. The three brands of chow tested were LabDiet 5,001 (LD5001), LabDiet 5,053 (LD5053), and Teklad 2019S (TL2019S) from two companies (Research Diets and Envigo, respectively). Mice fed LD5001 and LD5053 displayed higher levels of alcohol consumption and preference compared to mice fed TL2019S. We also found that alcohol consumption and preference could be rapidly switched by changing the diet 48 h prior to alcohol administration. Sucrose, saccharin, and quinine preferences were not altered, suggesting that the diets did not alter sweet and bitter taste perception. We also found that mice fed LD5001 displayed increased quinine-resistant alcohol intake compared to mice fed TL2019S, suggesting that diets could influence the development of compulsive behaviors such as alcohol consumption. We profiled the gut microbiome of water- and alcohol-drinking mice that were maintained on different diets and found significant differences in bacterial alpha- and beta-diversities, which could impact the gut–brain axis signaling and alcohol consumption.

Lignin-containing cellulose nanofibrils (LCNFs) are mainly produced commercially from treated wood pulp, which can decrease some of the carbon-negative benefits of utilizing biomass feedstock. In this work, LCNFs are prepared from non-wood feedstocks, including agricultural residues such as hemp, wheat straw, and flax. These feedstocks allowed for the preparation of LCNFs with a variety of properties, including tailored hydrophobicity. The feedstocks and their subsequent LCNFs are extensively characterized to determine the roles that feedstocks play on the morphology and properties of their resultant LCNFs. The LCNFs were then incorporated into paper handsheets to study their usefulness in papermaking applications, which indicated good potential for the use of wheat straw LCNFs as a surface additive to improve the oil resistance coating.

Abstract Objective Millions of Americans are infected by influenza annually. A minority seek care in the emergency department (ED) and, of those, only a limited number experience severe disease or death. ED clinicians must distinguish those at risk for deterioration from those who can be safely discharged. Methods We developed random forest machine learning (ML) models to estimate needs for critical care within 24 h and inpatient care within 72 h in ED patients with influenza. Predictor data were limited to those recorded prior to ED disposition decision: demographics, ED complaint, medical problems, vital signs, supplemental oxygen use, and laboratory results. Our study population was comprised of adults diagnosed with influenza at one of five EDs in our university health system between January 1, 2017 and May 18, 2022; visits were divided into two cohorts to facilitate model development and validation. Prediction performance was assessed by the area under the receiver operating characteristic curve (AUC) and the Brier score. Results Among 8032 patients with laboratory‐confirmed influenza, incidence of critical care needs was 6.3% and incidence of inpatient care needs was 19.6%. The most common reasons for ED visit were symptoms of respiratory tract infection, fever, and shortness of breath. Model AUCs were 0.89 (95% CI 0.86–0.93) for prediction of critical care and 0.90 (95% CI 0.88–0.93) for inpatient care needs; Brier scores were 0.026 and 0.042, respectively. Importantpredictors included shortness of breath, increasing respiratory rate, and a high number of comorbid diseases. Conclusions ML methods can be used to accurately predict clinical deterioration in ED patients with influenza and have potential to support ED disposition decision‐making.

Abstract Meiotic recombination requires the specific RecA homolog DMC1 recombinase to stabilize strand exchange intermediates in most eukaryotes. Normal DMC1 levels are crucial for its function, yet the regulatory mechanisms of DMC1 stability are unknown in any organism. Here, we show that the degradation of Arabidopsis DMC1 by the 26S proteasome depends on F-box proteins RMF1/2-mediated ubiquitination. Furthermore, RMF1/2 interact with the Skp1 ortholog ASK1 to form the ubiquitin ligase complex SCFRMF1/2. Genetic analyses demonstrate that RMF1/2, ASK1 and DMC1 act in the same pathway downstream of SPO11-1 dependent meiotic DNA double strand break formation and that the proper removal of DMC1 is crucial for meiotic crossover formation. Moreover, six DMC1 lysine residues were identified as important for its ubiquitination but not its interaction with RMF1/2. Our results reveal mechanistic insights into how the stability of a key meiotic recombinase that is broadly conserved in eukaryotes is regulated.

ObjectiveThe University of California (UC) leadership sought to develop a robust educational response to the epidemic of opioid-related deaths. Because the contributors to this current crisis are multifactorial, a comprehensive response requires educating future physicians about safe and effective management of pain, safer opioid prescribing, and identification and treatment of substance use disorder (SUD).MethodsThe six UC medical schools appointed an opioid crisis workgroup to develop educational strategies and a coordinated response to the opioid epidemic. The workgroup had diverse specialty and disciplinary representation. This workgroup focused on developing a foundational set of educational competencies for adoption across all UC medical schools that address pain, SUD, and public health concerns related to the opioid crisis.ResultsThe UC pain and SUD competencies were either newly created or adapted from existing competencies that addressed pain, SUD, and opioid and other prescription drug misuse. The final competencies covered three domains: pain, SUD, and public health issues related to the opioid crisis.ConclusionsThe authors present a novel set of educational competencies as a response to the opioid crisis. These competencies emphasize the subject areas that are fundamental to the opioid crisis: pain management, the safe use of opioids, and understanding and treating SUD.

Klein et al. use mobility data to forecast COVID-19 admissions for five Massachusetts hospitals. Combining aggregated mobile device data about users’ contact patterns, commuting volume, and mobility range with COVID hospitalizations and test-positivity data increases the lead-time of accurate predictions for individual hospitals.

Introduction People who inject drugs (PWID) have remained a contributor to the consistent HIV incidence rates in the US for decades. Pre-exposure prophylaxis (PrEP) is a promising biomedical intervention for HIV prevention among individuals at risk for HIV infection, including PWID. However, PWID report the lowest rates of PrEP uptake and adherence among at-risk groups. Tailored HIV prevention interventions must include strategies that compensate for cognitive dysfunction among PWID.Methods and analysis Using the multiphase optimisation strategy, we will be conducting a 16-condition factorial experiment to investigate the effects of four different accommodation strategy components to compensate for cognitive dysfunction among 256 PWID on medication for opioid use disorder. This innovative approach will inform optimisation of a highly effective intervention to enhance PWID’s ability to process and utilise HIV prevention content to improve PrEP adherence and HIV risk reduction in a drug treatment setting.Ethics and dissemination The institutional review board at the University of Connecticut approved this protocol (H22-0122) with an institutional reliance agreement with APT Foundation Inc. All participants are required to sign an informed consent form prior to engaging in any study protocols. The results of this study will be disseminated on national and international platforms through presentations at major conferences and journals.Trial registration number NCT05669534.

IntroductionThe imperative of medicine is to treat suffering and to cure when possible. This learning module has been designed to expand providers' knowledge of how to sustain life, restore health, relieve suffering, and provide comfort for people who are experiencing cancer-induced pain. The module uses cancer pain as the context through which students can learn interprofessional, team-based, and person-centered approaches to delivery of care.MethodsUsing the facilitator's guide, handouts, and other materials developed for this project, the module can be delivered as an in-person training session (approximately 120 minutes) for small groups of learners (teams of eight to 12 students drawn from multiple health care professions or schools). Prelearning materials and postsession activities are included that can enhance the experience.ResultsThis module was developed and tested with two pilot programs that were evaluated with focus groups, direct observation, and a postsession survey completed by learners. Data demonstrated high approval of and appreciation for the content and structure of the module by both learners and facilitators.DiscussionMany learners work with other health care professionals in their clinical experiences but have not had opportunities to effectively work in interprofessional collaborative practice. This interprofessional education activity allows students from disparate health professions to work together to identify patient-centered treatment options through interprofessional collaborative teamwork in a classroom setting.

OBJECTIVE:To evaluate whether anterior cervical spine surgery offers sustained (7 years) relief in patients with cervicogenic headaches (CGHs), and evaluate the difference between cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) for 1 and 2-level surgeries from a multicenter randomized clinical trial. METHODS:A post hoc analysis was performed of 575 patients who underwent one or 2-level CDA or ACDF for symptomatic cervical spondylosis as part of a prospective randomized clinical trial. Assessment of pain and functional outcome was done with the Neck Disability Index (NDI) in the trial. We used the NDI headache component to assess headache outcome. RESULTS:For both 1- and 2-level CDA and ACDF groups, there was significant headache improvement from preoperative baseline out to 7 years (p < 0.0001). For 1-level surgeries, headache improvement was similar for both groups at the 7-year point. For 2-level treatment, CDA patients had significantly improved headache scores versus ACDF patients at the 7-year point (p = 0.016). CONCLUSION:The headache improvement noted at early follow-up was sustained over the long-term period with ACDF and CDA populations. In the case of 2-level operations, CDA patients demonstrated significantly greater benefit compared to ACDF patients over the long-term. Sinuvertebral nerve irritation at the unco-vasculo-radicular junction and anterior dura may be the cause of CGH. Therefore, it is possible that improved cervical kinematics and preservation of range of motion at adjacent uncovertebral joints in CDA may contribute to the observed difference between the groups.

ObjectiveTo develop an evidence-based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA.MethodsWe identified clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available educational, behavioral, psychosocial, physical, mind-body, and pharmacologic therapies for OA. Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, including rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations.ResultsBased on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self-efficacy and self-management programs, tai chi, cane use, hand orthoses for first carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinflammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exercises, yoga, cognitive behavioral therapy, kinesiotaping for first CMC OA, orthoses for hand joints other than the first CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, duloxetine, and tramadol.ConclusionThis guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision-making that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Introduction: While emergency department (ED) crowding has deleterious effects on patient care outcomes and operational efficiency, impacts on the experience for patients discharged from the ED are unknown. We aimed to study how patient-reported experience is affected by ED crowding to characterize which factors most impact discharged patient experience. Methods: This institutional review board-exempt, retrospective, cohort study included all discharged adult ED patients July 1, 2020–June 30, 2021 with at least some response data to the the National Research Corporation Health survey, sent to most patients discharged from our large, academic medical center ED. Our query yielded 9,401 unique encounters for 9,221 patients. Based on responses to the summary question of whether the patient was likely to recommend our ED, patients were categorized as “detractors” (scores 0–6) or “non-detractors” (scores 7–10). We assessed the relationship between census and patient experience by 1) computing percentage of detractors within each care area and assessing for differences in census and boarder burden between detractors and non-detractors, and 2) multivariable logistic regression assessing the relationship between likelihood of being a detractor in terms of the ED census and the patient’s last ED care area. A second logistic regression controlled for additional patient- and encounter-specific covariates. Results: Survey response rate was 24.8%. Overall, 13.9% of responders were detractors. There was a significant difference in the average overall ED census for detractors (average 3.70 more patients physically present at the time of arrival, 95% CI 2.33–5.07). In unadjusted multivariable analyses, three lower acuity ED care areas showed statistically significant differences of detractor likelihood with changes in patient census. The overall area under the curve (AUC) for the unadjusted model was 0.594 (CI 0.577–0.610). The adjusted model had higher AUC (0.673, CI 0.657–.690]; P