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Caliciviruses are a diverse group of non-enveloped, positive-sense RNA viruses with a wide range of hosts and transmission routes. Norovirus is the most well-known member of the Caliciviridae ; the acute gastroenteritis caused by human norovirus (HuNoV), for example, frequently results in closures of hospital wards and schools during the winter months. One area of calicivirus biology that has gained increasing attention over the past decade is the conformational flexibility exhibited by the protruding (P) domains of the major capsid protein VP1. This was observed in structure analyses of capsids encoded by many species and is often a consequence of environmental cues such as metal ions, changes to pH, or receptor/co-factor engagement. This review summarises the current understanding of P-domain flexibility, discussing the role this region plays in caliciviral infection and immune evasion, and highlighting potential avenues for further investigation.

Background: Emerging adults aged 18-30 years face challenges during life transitions, with an added burden of navigating the health care system and additional costs associated with diabetes. This stress is compounded by overall low levels of health insurance literacy in this population, as people may not know about available financial and health care resources to minimize suboptimal diabetes outcomes. This study aimed to tailor a financial and health insurance toolkit to emerging adults with type 1 diabetes, including racially, ethnically diverse, and Medicaid-insured individuals, through community-based participatory action research., Methods: An academic research team and community members from a national organization held six online community advisory board (CAB) content-creation meetings to understand how to tailor a financial and health insurance Toolkit. The CAB was comprised of six racially and insurance-diverse emerging adults with type 1 diabetes and four content experts (clinical, financial, and insurance). Six 60-minute online CAB meetings were held via University Hospitals (UH)-encrypted Zoom over five months. Pre-reading materials were emailed to CAB members before the meetings. A moderator established the purpose of each meeting and briefly discussed meeting rules before each meeting commenced. During the meetings, the moderator guided the discussions and provided the CAB members opportunities to respond and build on one another's feedback. A deductive thematic qualitative analysis was utilized. Three researchers independently coded the cross-referenced and de-identified CAB meeting transcripts and then convened to reach a group consensus. Two CAB members performed member-checking., Results: The following key themes emerged to tailor the Toolkit: ensuring that content covers empowerment and self-advocacy, including genuine stories and multimedia visuals for aesthetics, addressing clinician bias, acknowledging racial and ethnic disparities in care, incorporating cultural representation, and demystifying Medicaid stigma., Conclusions: By successfully partnering with the CAB and a community organization through a community-based participatory action research approach, we will develop a financial and health insurance Toolkit tailored to the needs of racially and ethnically diverse and Medicaid-insured emerging adults with type 1 diabetes., (© 2024. The Author(s).)

Objective: Previous studies have assessed potential risk factors for vasomotor symptoms (VMS) beginning in midlife. We examined whether early adulthood risk factors predict VMS trajectories over time., Methods: We performed a secondary data analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based cohort. We included women who answered questions about VMS at three or more examinations (n = 1,966). We examined whether risk factors at baseline (when participants were aged 18-30 y; average age, 25 y) and the year 15 (Y15) exam (at ages 33-45 y; average age, 40 y) were associated with VMS trajectories from Y15 through Y35. Logistic regression models were used to evaluate the associations with VMS trajectories., Results: We identified three trajectories of VMS presence: minimal (40%), increasing over time (27%), and persistent (33%). Baseline factors associated with persistent VMS over time included Black race, less than a high school education, depressive symptoms, migraines, cigarette use, and at Y15 hysterectomy. Baseline factors associated with increasing VMS over time included Black race and lower body mass index. Risk factors for bothersome VMS were similar and also included thyroid disease, although thyroid disease was not associated with persistence of VMS over time. Associations were similar among women who had not undergone hysterectomy and in Black and White women., Conclusions: Risk factors for VMS may be identified in early adulthood. Further examination of risk factors such as migraines and depressive symptoms in early adulthood may be helpful in identifying therapies for VMS., Competing Interests: Financial disclosures/conflicts of interest: Abbi Lane received past institutional funding from Nutrasource. Richard J. Auchus did contracted research for Neurocrine Biosciences/Diurnal LTD, Spruce Biosciences, Corcept Therapeutics, and Sparrow Pharmaceuticals, and was a consultant for Quest Diagnostics, Corcept Therapeutics, Xeris Pharmaceuticals, Crinetics Pharmaceuticals, Adrenas Therapeutics, PhaseBio Pharmaceuticals, Novo Nordisk, Neurocrine Biosciences/Diurnal LTD, Recordati Rare Diseases, H Lundbeck A/S, and Sparrow Pharmaceuticals. The other authors have nothing to disclose., (Copyright © 2024 by The Menopause Society.)

Enveloped viruses encode specialised glycoproteins that mediate fusion of viral and host membranes. Discovery and understanding of the molecular mechanisms of fusion have been achieved through structural analyses of glycoproteins from many different viruses, and yet the fusion mechanisms of some viral genera remain unknown. We have employed systematic genome annotation and AlphaFold modelling to predict the structures of the E1E2 glycoproteins from 60 viral species in the Hepacivirus, Pegivirus, and Pestivirus genera. While the predicted structure of E2 varied widely, E1 exhibited a very consistent fold across genera, despite little or no similarity at the sequence level. Critically, the structure of E1 is unlike any other known viral glycoprotein. This suggests that the Hepaci-, Pegi-, and Pestiviruses may possess a common and novel membrane fusion mechanism. Comparison of E1E2 models from various species reveals recurrent features that are likely to be mechanistically important and sheds light on the evolution of membrane fusion in these viral genera. These findings provide new fundamental understanding of viral membrane fusion and are relevant to structure-guided vaccinology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Oliver et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The purpose of the study was to provide initial evidence for the internal consistency and convergent validity of the nine-item avoidant/restrictive food intake disorder screen (NIAS) in a sample of transgender and nonbinary (TGNB) youth and young adults., Methods: Returning patients at a Midwestern gender clinic ( n =164) ages 12-23 completed the NIAS, sick, control, one stone, fat, food (SCOFF), patient health questionnaire 9 (PHQ-9), and generalized anxiety disorder 7 (GAD-7) during their clinic visit. Age, sex assigned at birth, gender identity, weight, and height were also collected. Confirmatory factor analysis was used to establish the hypothesized three-factor structure of the NIAS in this sample. Relationships between the NIAS subscales and anthropometric data, SCOFF, PHQ-9, GAD-7, and sex assigned at birth were explored for convergent and divergent validity, and proposed screening cutoff scores were used to identify the prevalence of likely avoidant/restrictive food intake disorder (ARFID) in this population., Results: The three-factor structure of the NIAS was an excellent fit to the current data. Approximately one in five (22%) of the participants screened positive for ARFID. Approximately one in four participants scored above the picky eating (27.4%) or appetite (23.9%) cutoffs. Assigned female at birth participants scored significantly higher on the NIAS-Total, Appetite, and Fear subscales than those assigned male at birth. NIAS-Total was significantly related to all convergent validity variables other than age, with a moderate-strong correlation with other symptom screeners (SCOFF, PHQ-9, GAD-7), and a small negative correlation with body mass index percentile., Conclusions: Evidence supports the NIAS as a valid measure to screen for ARFID among TGNB youth and young adults., Competing Interests: No competing financial interests exist., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

E1 and E2 (E1E2), the fusion proteins of Hepatitis C Virus (HCV), are unlike that of any other virus yet described, and the detailed molecular mechanisms of HCV entry/fusion remain unknown. Hypervariable region-1 (HVR-1) of E2 is a putative intrinsically disordered protein tail. Here, we demonstrate that HVR-1 has an autoinhibitory function that suppresses the activity of E1E2 on free virions; this is dependent on its conformational entropy. Thus, HVR-1 is akin to a safety catch that prevents premature triggering of E1E2 activity. Crucially, this mechanism is turned off by host receptor interactions at the cell surface to allow entry. Mutations that reduce conformational entropy in HVR-1, or genetic deletion of HVR-1, turn off the safety catch to generate hyper-reactive HCV that exhibits enhanced virus entry but is thermally unstable and acutely sensitive to neutralising antibodies. Therefore, the HVR-1 safety catch controls the efficiency of virus entry and maintains resistance to neutralising antibodies. This discovery provides an explanation for the ability of HCV to persist in the face of continual immune assault and represents a novel regulatory mechanism that is likely to be found in other viral fusion machinery., Competing Interests: LS, MK, CL, MP, LW, TD, WL, DM, MK, GG, DB, WR, CI, AS, JG No competing interests declared, ZK Where authors are identified as personnel of the International Agency for Research on Cancer/WHO, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/WHO, (© 2022, Stejskal, Kalemera et al.)

Geriatric physical therapy requires a unique skill set and knowledge to provide best practice care. The skill set requires clinicians to recognize the significance of the continuum of aging from optimal to pathology-influenced aging and how psychosocial, environmental, behavioral, accessibility, and economic factors affect this aging continuum, optimal health, and wellness. Employing this distinctive skill set while also utilizing evidence-based practice, acknowledging the variability observed in older adults, and utilizing interwoven care systems that impact outcomes are key characteristics of best practice. The Academy of Geriatric Physical Therapy developed best practice guidelines consisting of 6 principles needed to ensure patients receive the care that they deserve. Best practice principles include person-centered care, anti-ageist beliefs, holistic assessment using sound outcome measures, evidence-based interventions, physical activity promotion, and interprofessional collaborative practice. This executive summary presents these principles along with suggested action steps for each element of best practice. The aims are to encourage individual self-assessment, promote improvement in practice on an individual and facility/system level, increase communication and collaboration with other health care providers about global best practices for older adults, and to further target education, resources, and advocacy toward achieving best practice on a larger scale., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 APTA Geriatrics, An Academy of the American Physical Therapy Association.)

Exercise is associated with protective effects, yet most adult women in this country do not meet the physical activity recommendations set forth in the Physical Activity Guidelines for Americans. This article discusses how exercise affects disease and prevents functional decline. It also clarifies why exercise is not a generic cure-all but is instead a tool physicians can use with precision to affect a myriad of health issues. Specifics will be provided regarding physical fitness assessments and comprehensive treatments and how physicians can be more involved in using physical fitness to keep their older female patients healthy., Competing Interests: Disclosure The authors have no commercial or financial conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to describe the prevalence of and relationships among disordered eating, food insecurity, and weight status among transgender and gender nonbinary youth and young adults. Methods: This cross-sectional study involved a screening protocol to assess disordered eating and food insecurity risk from September to December of 2019 at a gender clinic using five validated measures: (1) previous eating disorder diagnosis (yes/no); (2) Sick, Control, One Stone, Fat, Food Questionnaire (SCOFF); (3) Adolescent Binge Eating Disorder Questionnaire (ADO-BED); (4) Nine-Item Avoidant/Restrictive Food Intake Disorder Screen (NIAS); and (5) Hunger Vital Sign. Age, assigned sex at birth, gender identity, stage of medical transition, and body mass index were collected. Pearson's r correlation coefficients, between-groups t -tests, one-way analysis of variance tests, and Tukey's honest significant difference test were used to characterize the relationships between variables. Results: A total of 164 participants ages 12-23 years completed the screener. Using assigned sex at birth, 1.8% were underweight, 53% were a healthy weight, 17.1% were overweight, and 28.0% were obese. An estimated 8.7% reported a previous eating disorder diagnosis, 28.0% screened positive on the SCOFF, 9.1% on the ADO-BED, 75.0% on the NIAS, and 21.2% on the Hunger Vital Sign. Transgender males scored higher on the NIAS than transgender females ( p  = 0.03). Those with a previous eating disorder diagnosis scored significantly higher on the Hunger Vital Sign ( p  < 0.05). Conclusion: Gender clinics should routinely screen for disordered eating, food insecurity, overweight, and obesity to identify patients in need of further evaluation and referral.

Phelgmasia cerulea dolens (PCD) is a rare cause of shock that can complicate deep venous thrombosis and carries a high risk of mortality. We present a case of extensive bilateral lower extremity deep vein thrombosis associated with an inferior vena cava filter which rapidly progressed to PCD and refractory shock.

The development of cell therapy for repairing damaged or diseased skeletal muscle has been hindered by the inability to significantly expand immature, transplantable myogenic stem cells (MuSCs) in culture. To overcome this limitation, a deeper understanding of the mechanisms regulating the transition between activated, proliferating MuSCs and differentiation-primed, poorly engrafting progenitors is needed. Here, we show that methyltransferase Setd7 facilitates such transition by regulating the nuclear accumulation of β-catenin in proliferating MuSCs. Genetic or pharmacological inhibition of Setd7 promotes in vitro expansion of MuSCs and increases the yield of primary myogenic cell cultures. Upon transplantation, both mouse and human MuSCs expanded with a Setd7 small-molecule inhibitor are better able to repopulate the satellite cell niche, and treated mouse MuSCs show enhanced therapeutic potential in preclinical models of muscular dystrophy. Thus, Setd7 inhibition may help bypass a key obstacle in the translation of cell therapy for muscle disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Skeletal muscle adipose tissue (AT) infiltration (myosteatosis) increases with aging and may contribute to the development of Type 2 diabetes mellitus (T2DM). It remains unclear if myosteatosis is associated to glucose and insulin homeostasis independent of total and central adiposity., Design and Methods: The association between intermuscular AT (IMAT) in the abdominal skeletal muscles (total, paraspinal, and psoas) and fasting serum glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) in 393 nondiabetic Caucasian men aged 65+ was evaluated. Abdominal IMAT, visceral AT (VAT), and subcutaneous AT (SAT) (cm(3) ) were measured by quantitative computed tomography at the L4-L5 intervertebral space., Results: In age, study site, height, and muscle volume adjusted regression analyses, total abdominal and psoas (but not paraspinal) IMAT were positively associated with glucose, insulin, and HOMA-IR (all P < 0.003). The associations between total abdominal and psoas IMAT and insulin and HOMA-IR remained significant after further adjusting for lifestyle factors, as well as duel-energy x-ray absorptiometry (DXA) measured total body fat, VAT, or SAT in separate models (all P < 0.009)., Conclusions: A previously unreported, independent association between abdominal myosteatosis and hyperinsulinemia and insulin resistance among older Caucasian men was indicated. These associations may be specific for particular abdominal muscle depots, illustrating the potential importance of separately studying specific muscle groups., (Copyright © 2013 The Obesity Society.)

Active learning techniques encourage students to participate in acquiring skills and knowledge. One technique that encourages active learning is patient simulation. Patient simulation tools can range from simple part-task trainers to complex high-fidelity simulators. A variety of human simulators can be used to teach basic patient care skills or more complex skills such as trauma management. Simulation research has demonstrated students can improve scores on standardized tests as well as improve their confidence. Research is still needed to address the long-term impact of patient simulation training. Although simulations have gained popularity, researchers caution that they should always be used as part of clinical education and not as a substitute., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: To demonstrate how principal components analysis can be used to describe patterns of weight changes in response to an intensive lifestyle intervention., Methods: Principal components analysis was applied to monthly percent weight changes measured on 2,485 individuals enrolled in the lifestyle arm of the Action for Health in Diabetes (Look AHEAD) clinical trial. These individuals were 45 to 75 years of age, with type 2 diabetes and body mass indices greater than 25 kg/m(2). Associations between baseline characteristics and weight loss patterns were described using analyses of variance., Results: Three components collectively accounted for 97.0% of total intrasubject variance: a gradually decelerating weight loss (88.8%), early versus late weight loss (6.6%), and a mid-year trough (1.6%). In agreement with previous reports, each of the baseline characteristics we examined had statistically significant relationships with weight loss patterns. As examples, males tended to have a steeper trajectory of percent weight loss and to lose weight more quickly than women. Individuals with higher hemoglobin A(1c) (glycosylated hemoglobin; HbA(1c)) tended to have a flatter trajectory of percent weight loss and to have mid-year troughs in weight loss compared to those with lower HbA(1c)., Conclusions: Principal components analysis provided a coherent description of characteristic patterns of weight changes and is a useful vehicle for identifying their correlates and potentially for predicting weight control outcomes.

Background: Obesity in the United States has increased significantly during the past several decades. The role of calcium in the maintenance of a healthy body weight remains controversial., Methods: A randomized, double-blinded, placebo-controlled trial was performed with 36 282 postmenopausal women, aged 50 to 79 years, who were already enrolled in the dietary modification and/or hormone therapy arms of the Women's Health Initiative clinical trial. Women were randomized at their first or second annual visit to receive a dose of 1000 mg of elemental calcium plus 400 IU of cholecalciferol (vitamin D) or placebo daily. Change in body weight was ascertained annually for an average of 7 years., Results: Women receiving calcium plus cholecalciferol supplements vs women receiving placebo had a minimal but consistent favorable difference in weight change (mean difference, -0.13 kg; 95% confidence interval, -0.21 to -0.05; P = .001). After 3 years of follow-up, women with daily calcium intakes less than 1200 mg at baseline who were randomized to supplements were 11% less likely to experience small weight gains (1-3 kg) and 11% less likely to gain more moderate amounts of weight (>3 kg) (P for interaction for baseline calcium intake = .008)., Conclusion: Calcium plus cholecalciferol supplementation has a small effect on the prevention of weight gain, which was observed primarily in women who reported inadequate calcium intakes., Trial Registration: clinicaltrials.gov Identifier: NCT00000611.

Patients age 50 and older who are seen by primary care doctors are in various stages of wellness, ranging from healthy to frail. Because of this diversity, exercise prescription needs to be individualized, based on many of the same principles as drug prescription. Fitness programs typically include exercises to improve posture, aerobics, flexibility, strength, and balance. Exercising for 5 minutes a day is a good starting point, with sessions increasing gradually to 20 to 30 minutes. Trunk strengthening exercise can help patients stand from soft, low chairs. Ankle exercises can reduce the risk of falls and hip fractures. Weight training is safe and effective exercise for older patients.

Exercise provides important benefits for older adults in the areas of cardiovascular function, strength and muscle mass, postural stability, and psychological function. These benefits can be achieved by those who are healthy, as well as by the frail and very old. Physicians can use a simple screening test to identify patients at risk for loss of mobility and function due to muscle weakness. Exercise helps prevent hip fractures from falls by increasing bone density, coordination, balance, and muscle strength. It is also an important treatment for patients with arthritis, Parkinson's disease, stroke, and other chronic diseases of aging. Patients who exercise show improvements in depressive symptoms and sleep disorders.

Most older Americans are not physically fit and do not exercise regularly. This is especially true of older women, who are weaker than men and become disabled and dependent in the later years at a much greater rate. Exercise can increase the body's metabolism and make it more efficient in burning calories. Physical fitness also makes respiration more efficient. Evidence suggests strongly that the physically fit live 2 to 3 years longer and have a better quality of life than sedentary individuals. Any time is the best time for a person of any age to start exercising. Exercise is movement--dancing, walking, lifting a weight, using the body. Older individuals tend to be willing to exercise if they are given appropriate recommendations and follow-up.

The Multicenter Automatic Defibrillator Implantation Trial (MADIT) showed improved survival with defibrillator therapy but was restricted to coronary artery disease patients with nonsustained ventricular tachycardia (NSVT) and inducible nonsupressible VT. The outcome of patients without inducible VT or inducible but suppressed VT still remains unclear. We performed risk stratification at electrophysiologic (EP) study in 111 consecutive unselected patients with nonsustained VT and coronary artery disease and randomized them to drug or device therapy. Follow-up on selected therapy was 1-71 (mean 27 +/- 20) months. Of 111 patients, 39 patients (35%) had inducible sustained VT at baseline EP study and were stratified to a "higher" risk group (group 1) for sudden death. In 9 of these patients (group 1A), sustained VT was suppressed with class IA antiarrhythmic drugs; in the remaining 30 patients (group 1B) sustained VT was not suppressed with class IA antiarrhythmic drugs. The other 72 of 111 patients (65%) had no inducible sustained VT at EP study and were stratified to a "lower"-risk group (group 2) for sudden death. Mean LVEF in group 1 was 30 +/- 10% versus 37 +/- 9% in group 2 (p = 0.001). Selected therapy in group 1 was an implantable cardioverter defibrillator (16 patients) or guided drug therapy (electrophysiologically guided class I antiarrhythmic drugs = 7 patients; Holter-guided class III antiarrhythmic drugs = 16 patients). In group 2, empiric drug therapy included beta blockers in 29 patients or Holter-guided class III antiarrhythmic drugs in 17 patients, with no antiarrhythmic drug therapy being administered in 26 patients. Mean LVEF tended to be lower in patients receiving class III antiarrhythmic drug therapy (34 +/- 12%) than in patients receiving beta blockers (40 +/- 10%, p = 0.06). Three-year total survival was comparable in group 1 (70%) and in group 2 (81%), but sudden cardiac death mortality tended to be lower in group 1 versus group 2 (0 vs 9%, p = 0.09). Patients receiving class III antiarrhythmic therapy had significantly higher 3-year all cause (40%, p = 0.04) and sudden death (25%, p = 0.06) mortality than patients receiving beta blockers (17% and 8% respectively) or no antiarrhythmic drug therapy (4% and 0%, respectively). The following conclusions can be drawn from this analysis: (1) Electrophysiologically guided drug therapy and implantable defibrillators can minimize the risk of sudden cardiac death in patients with coronary artery disease and inducible sustained VT stratified to higher risk of sudden death. A comparable outcome with respect to sudden death prevention in drug-suppressed or drug-refractory patients suggests limited prognostic benefit of class IA drug testing. (2) Lower-risk patients with severely depressed LVEF and minimal or no symptoms do not have a favorable outcome with respect to sudden and all-cause mortality on Holter-guided class III drug therapy. However, asymptomatic patients with mildly depressed left ventricular function have low sudden death event rates on beta blocker or no antiarrhythmic drug therapy.