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Exposure to temperatures outside of a fish's optimal range results in suppression of the immune system, ultimately leaving aquaculture stocks susceptible to disease outbreaks. This effect is exacerbated in triploid fishes, which demonstrate greater susceptibility to stress than their diploid counterparts. This study investigates the impacts of acute heat stress on the abundance of immune transcripts and proteins in diploid and triploid Chinook salmon (Oncorhynchus tshawytscha), an important finfish crop. This study also demonstrates that acute heat stress induces significant increases in the abundance hsp70, hsp90 and il1b transcripts in the head kidneys, gills and heart ventricles of both diploid and triploid Chinook salmon. Widespread dysregulation of antigen-presentation transcripts was also observed in fish of both ploidies. These results suggest that acute heat stress activates acute-phase responses in Chinook salmon and dysregulates antigen presentation, potentially leaving fish more susceptible to infection. At the protein level, IL-1β was differentially expressed in the head kidney and ventricles of diploid and triploid salmon following heat shock. Differential expression of two tapasin-like proteins in diploid and triploid salmon subjected to heat shock was also observed. Altogether, these data indicate that diploid and triploid Chinook salmon respond differently to acute thermal stressors., (© 2024 The Author(s). Journal of Fish Diseases published by John Wiley & Sons Ltd.)

Type 1 diabetes treatment stands at a crucial and exciting crossroad since the 2022 U.S. Food and Drug Administration (FDA) approval of teplizumab to delay disease development. In this Perspective article, we discuss four major conceptual and practical issues that emerged as key to further advance type 1 diabetes research and therapies. First, collaborative networks leveraging the synergy between the type 1 diabetes research and care community members are key to fostering innovation, know-how and translation into the clinical arena worldwide. Second, recent clinical trials in presymptomatic stage 2 and recent-onset stage 3 disease have shown the promise, and potential pitfalls, of using immunomodulatory and/or beta-cell protective agents to achieve sustained remission or prevention. Third, the increasingly appreciated heterogeneity of clinical, immunological, and metabolic phenotypes and disease trajectories is of critical importance to advance the decision-making process for tailored type 1 diabetes care and therapy. Fourth, the clinical benefits of early diagnosis of beta-cell autoimmunity warrant consideration of general population screening for islet autoantibodies, which requires further efforts to address the technical, organizational and ethical challenges inherent to a sustainable program. Efforts are underway to integrate these four concepts into the future directions of type 1 diabetes research and therapy., (© 2024 by the American Diabetes Association.)

Aims/hypothesis: Islet prohormone-processing enzymes convert peptide hormone precursors to mature hormones. Defective beta cell prohormone processing and the release of incompletely processed peptide hormones are observed prior to the onset of diabetes, yet molecular mechanisms underlying impaired prohormone processing during the development of diabetes remains largely unknown. Previous studies have shown that prohormone convertase 1/3 (PC1/3) protein and mRNA expression levels are reduced in whole islets from donors with type 1 diabetes, although whether PC1/3-mediated prohormone processing in alpha and beta cells is disrupted in type 1 diabetes remained to be explored. Herein, we aimed to analyse the expression of PC1/3 in islets from non-diabetic donors, autoantibody-positive donors and donors diagnosed with type 1 diabetes or type 2 diabetes., Methods: Immunostaining and high-dimensional image analysis were performed on pancreatic sections from a cross-sectional cohort of 54 donors obtained from the Network for Pancreatic Organ Donors with Diabetes (nPOD) repository, to evaluate PC1/3 expression patterns in islet alpha, beta and delta cells at different stages of diabetes., Results: Alpha and beta cell morphology were altered in donors with type 1 diabetes, including decreased alpha and beta cell size. As expected, the insulin-positive and PC1/3-positive areas in the islets were both reduced, and this was accompanied by a reduced percentage of PC1/3-positive and insulin-positive/PC1/3-positive cells in islets. PC1/3 and insulin co-localisation was also reduced. The glucagon-positive area, as well as the percentage of glucagon-positive and glucagon-positive/PC1/3-positive cells in islets, was increased. PC1/3 and glucagon co-localisation was also increased in donors with type 1 diabetes. The somatostatin-positive cell area and somatostatin staining intensity were elevated in islets from donors with recent-onset type 1 diabetes., Conclusions/interpretation: Our high-resolution histomorphological analysis of human pancreatic islets from donors with and without diabetes has uncovered details of the cellular origin of islet prohormone peptide processing defects. Reduced beta cell PC1/3 and increased alpha cell PC1/3 in islets from donors with type 1 diabetes pinpointed the functional deterioration of beta cells and the concomitant potential increase in PC1/3 usage for prohormone processing in alpha cells during the pathogenesis of type 1 diabetes. Our finding of PC1/3 loss in beta cells may inform the discovery of new prohormone biomarkers as indicators of beta cell dysfunction, and the finding of elevated PC1/3 expression in alpha cells may encourage the design of therapeutic targets via leveraging alpha cell adaptation in diabetes., (© 2024. The Author(s).)

Objectives: Cardiac surgery associated-acute kidney injury is a common and serious postoperative complication of cardiac surgery, which is associated with increased postoperative morbidity and mortality. This study aimed to explore the association between cardiopulmonary bypass (CPB) blood flow rate (BFR), and major adverse kidney events (MAKEs) at day 30., Design: Retrospective single-center before-after observational study. Patients were divided in 2 groups according to CPB flow rates: a first group with an institutional protocol targeting a CPB-BFR of >2.2 L/min/m² (low CPB-BFR group), and a second group with a modified institutional protocol targeting a CPB-BFR of >2.4 L/min/m² (high CPB-BFR group). The primary outcome was MAKE at 30 days, defined as the composite of death, renal replacement therapy or persistent renal dysfunction., Setting: The data were collected from clinical routines in university hospital., Participants: Adult patients who underwent elective and urgent cardiac surgery without severe chronic renal failure, for whom CPB duration was ≥90 minutes., Interventions: We included 533 patients (low CPB-BFR group, n = 270; high CPB-BFR group, n = 263)., Measurements and Main Results: A significant decrease in MAKE at 30 days was observed in the high CPB-BFR group (3% v 8%; odds ratio [OR], 0.779; 95% confidence interval [CI], 0.661-0.919; p < 0.001) mainly mediated by a lower 30-day mortality in the high CPB-BFR group (1% v 5%; OR, 0.697; 95% CI, 0.595-0.817; p = 0.001), as was renal replacement therapy (1% v 4%; OR, 0.739; 95% CI, 0.604-0.904; p = 0.016)., Conclusions: In patients undergoing cardiac surgery, increased CPB-BFR was associated with a decrease in MAKE at 30 days including mortality and renal replacement therapy., Competing Interests: Declaration of competing interest M.J.L. is cofounder and shareholder of the DiCARTECH company that has been created to build and sell a device that measure Capillary refill time. There are no direct competing interests with the data presented in this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background Secondary peritonitis (SP) arises from direct contamination of the peritoneum by spillage from the gastrointestinal or urogenital tracts. Objective This research aimed to evaluate the clinical and epidemiological characteristics of patients with SP undergoing surgical management and to study potential factors associated with morbidity and mortality in a reference hospital in Eastern Venezuela. Methodology A retrospective cross-sectional study was conducted on patients aged 18 to 80 undergoing surgical treatment for SP at "Dr. Luis Razetti" University Hospital in Barcelona, Anzoátegui state, Venezuela, between January and December 2022. We calculated odds ratios to assess mortality risks based on the presence of postoperative complications. Results Analysis of 168 adult patients revealed a predominantly male population (n=110, 65.5%) with a mean age of 35.63 years (SD=14.34). Generalized peritonitis was observed in 126 cases (75%), primarily originating from the appendix (n=117, 69.6%). Postoperative complications occurred in 18 patients (10.7%); sepsis represented the most common associated complication (n=10, 43.5%). Patients with secondary peritonitis associated with acute appendicitis had a lower mortality rate (p=0.042). Additionally, laparotomy was associated with higher frequencies of complications (p=0.001) and mortality (p=0.025), while open appendectomy showed lower frequencies of complications (p=0.002) and mortality (p=0.035). Notably, patients experiencing postoperative complications had a significantly elevated risk of mortality (OR=98, 95% confidence interval = 21.74 - 441.69). Conclusion The most common source of SP was appendicular. Patients undergoing exploratory laparotomy for the management of SP had a higher frequency of complications and mortality, whereas those undergoing open appendectomy had lower rates of complications and mortality., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. "Dr Luis Razetti" University Hospital Bioethical Committee issued approval Memorandum N° 254-HULR-2021. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, González-Guaimare et al.)

Introduction: Thrombectomy complications remain poorly explored. This study aims to characterize periprocedural intracranial vessel perforation including the effect of thrombolysis on patient outcomes., Patients and Methods: In this multicenter retrospective cohort study, consecutive patients with vessel perforation during thrombectomy between January 2015 and April 2023 were included. Vessel perforation was defined as active extravasation on digital subtraction angiography. The primary outcome was modified Rankin Scale (mRS) at 90 days. Factors associated with the primary outcome were assessed using proportional odds models., Results: 459 patients with vessel perforation were included (mean age 72.5 ± 13.6 years, 59% female, 41% received thrombolysis). Mortality at 90 days was 51.9% and 16.3% of patients reached mRS 0-2 at 90 days. Thrombolysis was not associated with worse outcome at 90 days. Perforation of a large vessel (LV) as opposed to medium/distal vessel perforation was independently associated with worse outcome at 90 days (aOR 1.709, p  = 0.04) and LV perforation was associated with poorer survival probability (HR 1.389, p  = 0.021). Patients with active bleeding >20 min had worse survival probability, too (HR 1.797, p  = 0.009). Thrombolysis was not associated with longer bleeding duration. Bleeding cessation was achieved faster by permanent vessel occlusion compared to temporary measures (median difference: 4 min, p  < 0.001)., Discussion and Conclusion: Vessel perforation during thrombectomy is a severe and frequently fatal complication. This study does not suggest that thrombolysis significantly attributes to worse prognosis. Prompt cessation of active bleeding within 20 min is critical, emphasizing the need for interventionalists to be trained in complication management., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: V. S.-Z. discloses speaker fees from Medtronic Inc. (money paid to institution). M.R.L. discloses unrestricted educational grants from Medtronic and Stryker; consulting for Medtronic, Stereotaxis, Metis Innovative and Aeaean Advisers; equity interest in Proprio, Fluid Biomed, Stroke Diagnostics, Hyperion Surgical, Apertur; editorial board of Journal of NeuroInterventional Surgery; data safety monitoring board of Arsenal Medical. M.-N.P. discloses unrestricted grants from Swiss National Science Foundation (SNF), Bangerter-Rhyner Stiftung, Stryker Neurovascular Inc., Phenox GmbH, Medtronic Inc., Rapid Medical Inc., and Penumbra Inc for the DISTAL trial, grant for SPINNERS trial from Siemens Healthineers AG (money paid to institution) and the following speaker fees: Stryker Neurovascular Inc., Medtronic Inc., Penumbra Inc., Acandis GmbH, Phenox GmbH, Rapid Medical Inc. and Siemens Healthineers AG (money paid to institution).

Background: The modified pouchitis disease activity index (mPDAI) based on clinical symptoms and endoscopic findings is used to diagnose pouchitis, but validated instruments to monitor pouchitis are still lacking. We recently established an endoscopic classification that described 7 endoscopic phenotypes with different outcomes. We assessed symptoms and compared mPDAIs among phenotypes in inflammatory bowel disease (IBD)., Methods: We retrospectively reviewed pouchoscopies and classified them into 7 main phenotypes: normal ( n  = 25), afferent limb (AL) involvement ( n  = 4), inlet involvement ( n  = 14), diffuse ( n  = 7), focal inflammation of the pouch body ( n  = 25), cuffitis ( n  = 18), and pouch-related fistulas ( n  = 10) with a single phenotype were included. Complete-case analysis was conducted., Results: One hundred and three IBD patients were included. The median mPDAI was 0 (IQR 0-1.0) in patients with a normal pouch. Among inflammatory phenotypes, the highest median mPDAI was 4.0 (IQR 2.25-4.75) in cuffitis, followed by 3.0 (IQR 2.5-4.0) in diffuse inflammation, 2.5 (IQR 1.25-4.0) in inlet involvement, 2.5 (IQR 2.0-3.5) in AL involvement, 2.0 (IQR 1.0-3.0) in focal inflammation, and 1.0 (IQR 0.25-2.0) in the fistula phenotype. Perianal symptoms were frequently observed in pouch-related fistulas (8/10, 80%) and cuffitis (13/15, 87%). Among patients with cuffitis, all had incomplete emptying (6/6, 100%)., Conclusions: We correlated the mPDAI with the endoscopic phenotypes and described the limited utility of symptoms in distinguishing between inflammatory phenotypes. Further studies are warranted to understand which symptoms should be monitored for each phenotype and whether mPDAI can be minimized after pouch normalization., Competing Interests: S.A., J.E.O., N.A.C., V.R., L.R.G., Y.Y., C.T., J.R., K.B.S., R.D.H., K.U., B.D.S., N.H.H., and A.S. have no relevant disclosures. R.D.C. is on the speaker’s bureau from AbbVie and Takeda. He is a consultant/advisor for AbbVie Laboratories, BM/celgene, Eli Lilly, Gilead Sciences, Janssen, Pfizer, Takeda, UCB Pharma. He has received clinical trial support/grants from Abbvie, BMS/Celgene, Boehringer Ingelheim, Crohn’s and Colitis Foundation of America, Genentech, Gilead Sciences, Hollister, Medimmune, Mesoblast Ltd., Osiris Therpeutics, Pfizer, Receptos, RedHill Biopharma, Sanofi-Aventis, Schwarz Pharma, Seres Therapeutics, Takeda Pharma, UCB Pharma. His wife is on the board of directors of Aerpio Therapeutics, Novus Therapeutics, Vital Therapeutics, Inc, and NantKwest. M.A.R. has served as a consultant for Pfizer. S.R.D. has served as a consultant for Pfizer and is on the speaker’s bureau for AbbVie. J.P. has received grant support from AbbVie and Takeda. He has served as a consultant for Veraste,. CVS Caremark and is on the advisory board for Takeda, Janssen and Pfizer. E.B.C. is the founder and chief medical officer of AVnovum Therapeutics. D.T.R. has received grant support from Takeda; and has served as a consultant for Abbvie, Altrubio, Amgen, AvaloTherapeutics, Bristol-Myers Squibb, Buhlmann Diagnostics Corp, Chronicles Health, ClostraBio, Connect BioPharma, Cytoki Pharma, Douglas Pharmaceuticals, EcoR1, Ferring Pharma, Image Analysis Group, Index Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Lilly, Odyssey Therapeutics, Pfizer, Prometheus Biosciences, Reistone Biopharma, Samsung Neurologica, Sangamo Therapeutics, Shanghai Pharma Biotherapeutics USA, Takeda, Tissium S.A., and Trellus Health., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Purpose: High doses of venous corticosteroids are currently the only validated treatment for the management of optic neuritis (ON). The objective is to assess the changes in visual function parameters after oral high-dose methylprednisolone in patients with ON., Methods: A retrospective analysis of patients with acute ON was performed. Patients received 1 g per day of oral methylprednisolone for 3 to 5 days. Visual function was measured using the ETDRS test for visual acuity, 30-2 automated visual field test, contrast sensitivity test, and color vision test before treatment, 4 days, 2 weeks, 1 month and 3 months, and 6 months following treatment. To assess anatomical changes, optical coherence tomography of the ganglion cells was performed at various timepoints., Results: Between September 2014 and September 2016, a total of 29 patients were included in the study. More than 80% of patients had recovered normal visual acuity after 3 and 6 months. This recovery of all parameters of visual function was observed as early as 4 days but occurred predominantly within 15 days after the initiation of treatment. We observed a thinning of the ganglion cell layer during the follow-up, which mainly occurs within one month. The P100 wave of visually evoked potentials was discernible in all patients at 6 months. During the 6 years of follow-up, 2 patients had experienced a relapse of ON. No serious adverse effects were observed., Conclusion: This study demonstrated a rapid recovery of all visual function parameters after oral high-dose methylprednisolone ON with no serious adverse effects., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background Postoperative complications (POC) are undesirable consequences of surgery and are a major area of concern adversely affecting the quality of surgical care and patient safety. Emergency surgery has been observed to have a higher incidence of different POC. The analysis of POC is of great importance due to their impact on the quality of life of patients and because they have become an indicator to measure the quality of hospital services. Objective This study aimed to describe the POC of emergency surgeries in patients from the general surgery department of a referral hospital in eastern Venezuela. Methodology A cross-sectional retrospective study was conducted, including patients undergoing emergency surgery at "Dr. Luis Razetti" University Hospital, Barcelona, Venezuela, between November 2022 and May 2023. Results Medical records of 178 patients were analyzed. Most were male (53.7%), with an average age of 34.98 and a standard deviation of 18.2 years. POC was registered in 28 (15.7%) patients, with surgical site infection being the most common in 21 (39.62%) patients. Those over 65 years old (21.4% vs. 6.4%, p=0.013), patients with a history of hypertension (25% vs. 6.3%, p=0.002), hypoalbuminemia (100% vs. 43.8%, p=0.027), diagnosed with peritonitis due to hollow viscus perforation (21.4% vs. 6%, p=0.007), trauma (25% vs. 9.3%, p=0.018), and those with a midline incision (75% vs. 31.3%, p<0.001) had a higher frequency of POC. There was a mortality rate of 2.8% with no significant difference based on the development of POC. Conclusion POC represents a significant cause of morbidity and mortality in patients undergoing emergency surgeries. The studied sample showed a similar frequency of POC compared to previous reports but with lower mortality. Complications were associated with higher frequencies of hypertension, midline approach, hypoalbuminemia, and emergency surgery for peritonitis due to hollow viscus perforation and trauma., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Castañeda-Marquez et al.)

Background The thoracic ultrasound (TUS) is a monitoring tool that has gained worldwide popularity in various scenarios, offering the opportunity for dynamic, bedside evaluations. Recent studies indicate that the use of TUS enables the diagnosis of pathologies resulting from blunt chest trauma (BCT), yielding favorable outcomes. This study aimed to compare the utility of TUS versus chest radiography (CXR) in diagnosing pulmonary pathologies resulting from closed-chest traumas. Methodology A prospective cross-sectional study was conducted with a sample of 58 patients diagnosed with BCT who sought emergency care at the "Dr. Luis Razetti" University Hospital in Barcelona, Venezuela, from November 2023 to January 2024. Results Of the patients, 75.9% (n = 44) were male, with an average age of 37.8 years (standard deviation = 18.4 years). Injuries were reported in 8.6% (n = 5) of the patients, including 60% (n = 3) pneumothorax and 40% (n = 2) hemothorax. Ultrasound results coincided with CXR in 94.8% (n = 55) of the cases, with a Cohen's kappa coefficient of 0.9 (95% confidence interval (CI) = 0.642-1.0). TUS demonstrated higher sensitivity than CXR (100% vs. 60%) for detecting hemothorax and pneumothorax in patients with BCT, with an area under the receiver operating characteristic curve of 0.991 (95% CI = 0.968-1.013). Conclusions BCT predominantly occurred in young males, resulting primarily in pneumothorax and hemothorax lesions, detectable with higher sensitivity through TUS compared to CXR. The use of TUS should be considered an essential component of the initial assessment for individuals with BCT., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Uzcategui-Gutierrez et al.)

In 2019, the US Department of Health and Human Services launched the Ending the HIV Epidemic in the US initiative (EHE) with the goal of reducing new HIV infections by 90% by 2030. This initiative identifies 4 pillars (diagnose, treat, prevent, and respond) to address the HIV epidemic in the United States. To advance the EHE goals, the Federal Bureau of Prisons (FBOP) has implemented interventions at all points of the HIV care continuum. The FBOP has addressed the EHE pillar of prevention through implementing preexposure prophylaxis, developing a strategy to decrease the risk of new HIV infection, and providing guidance to FBOP healthcare providers. This article describes the implementation of programs to improve the HIV care continuum and end the epidemic of HIV within the FBOP including a review of methodology to implement an HIV preexposure prophylaxis program.

Background Difficult laparoscopic cholecystectomy (DLC) denotes the surgical extraction of the gallbladder under circumstances where associated conditions within the same organ, adjacent structures, or patient-specific conditions impede a smooth, expeditious, and comfortable dissection. It is imperative to utilize tools that aid in anticipating this challenging surgical scenario, enabling the implementation of appropriate measures. Objective This study aimed to assess the effectiveness of the Labbad-Vivas score (LVS) in predicting DLC and its correlation with the Parkland Grading Scale (PGS). Methodology A prospective study was conducted, including patients diagnosed with gallstone disease undergoing LC (laparoscopic cholecystectomy) at the "Dr. Luis Razetti" University Hospital in Barcelona, Venezuela, between September and December 2023. Results Forty patients were studied, with 80% (n=32) being female and 95% (n=38) under the age of 65; surgeries were elective in 72.5% (n=29) of cases; 35% (n=14) had an LVS ≥16 (difficult cholecystectomy); and 62.5% (n=25) of patients presented Grades 1 and 2 on the PGS. Total cholecystectomy was performed in 95% (n=38) of the patients. The LVS showed a sensitivity of 80%, specificity of 92%, positive predictive value of 85.7%, and negative predictive value of 88.5% to predict DLC, with an area under the receiver operating characteristic curve of 0.897 (95% confidence interval (CI) = 0.792-1.003). A Pearson correlation coefficient of 0.805 (95% CI = 0.656 - 0.904) was obtained between both scores. Conclusion The use of the LVS score in the preoperative setting is feasible as a predictor of DLC, given its effectiveness and high correlation with the PGS., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Serrano-González et al.)

Coxsackievirus B (CVB) infection of pancreatic β cells is associated with β cell autoimmunity and type 1 diabetes. We investigated how CVB affects human β cells and anti-CVB T cell responses. β cells were efficiently infected by CVB in vitro, down-regulated human leukocyte antigen (HLA) class I, and presented few, selected HLA-bound viral peptides. Circulating CD8 + T cells from CVB-seropositive individuals recognized a fraction of these peptides; only another subfraction was targeted by effector/memory T cells that expressed exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with β cell antigen GAD. Infected β cells, which formed filopodia to propagate infection, were more efficiently killed by CVB than by CVB-reactive T cells. Our in vitro and ex vivo data highlight limited CD8 + T cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CD8 + T cells recognizing structural and nonstructural CVB epitopes provide biomarkers to differentially follow response to infection and vaccination.

Sleep and circadian rhythm disturbance are predictors of poor physical and mental health, including dementia. Long-term digital technology-enabled monitoring of sleep and circadian rhythms in the community has great potential for early diagnosis, monitoring of disease progression, and assessing the effectiveness of interventions. Before novel digital technology-based monitoring can be implemented at scale, its performance and acceptability need to be evaluated and compared to gold-standard methodology in relevant populations. Here, we describe our protocol for the evaluation of novel sleep and circadian technology which we have applied in cognitively intact older adults and are currently using in people living with dementia (PLWD). In this protocol, we test a range of technologies simultaneously at home (7-14 days) and subsequently in a clinical research facility in which gold standard methodology for assessing sleep and circadian physiology is implemented. We emphasize the importance of assessing both nocturnal and diurnal sleep (naps), valid markers of circadian physiology, and that evaluation of technology is best achieved in protocols in which sleep is mildly disturbed and in populations that are relevant to the intended use-case. We provide details on the design, implementation, challenges, and advantages of this protocol, along with examples of datasets.

Background: Community initiatives can shape health behaviors, such as physical activity and dietary habits, across a population and help reduce the risk of developing chronic disease. To achieve this goal and impact health outcomes, Pasadena Vibrant Community aimed to engage communities in an ongoing dialogue about the importance of healthy behaviors, implement and advance community-based strategies to promote health, and improve diet and physical activity behaviors. The initiative was centered around a collaboration between a backbone organization, steering committee, and 7 collaborating organizations funded to implement multicomponent, evidence-based programs.. The common agenda was detailed in a community action plan, which included 19 interventions targeting healthy eating and active living among adults and youth in Pasadena, Texas., Methods: A mixed methods evaluation of the initiative was conducted over 4 years. Data sources included document reviews of quarterly progress reports (n = 86) and supplemental data reports (n = 16) provided by collaborating organizations, annual Steering Committee surveys (n = 4), and interviews conducted with staff from a subset of Collaborating Organizations (n = 4)., Results: The initiative reached over 50,000 community members per year through 19 evidence-based interventions and impacted health outcomes, including knowledge and adoption of healthy eating practices and increased physical activity. Thirty-one systems-level changes were implemented during the initiative, including 16 environmental changes. Steering Committee meetings and shared goals enabled connections, communication, and cooperation, which allowed Collaborating Organizations to address challenges and combine resources to deliver their programs., Conclusions: Community initiatives can effectively permeate the community by reaching individuals, improving physical activity and dietary habits, and ensuring sustainability. Based on the experience reported here, the success of a community initiative can be facilitated if collaborating organizations come together to implement evidence-based interventions and tailor them to the community, and if they are empowered by significant leadership and supportive collaboration and aligned by a common agenda., (© 2024. The Author(s).)

Despite antiretroviral therapy (ART), chronic forms of HIV-associated neurocognitive disorders (HAND) affect an estimated 50% of individuals living with HIV, greatly impacting their quality of life. The prevailing theory of HAND progression posits that chronic inflammation arising from the activation of latent viral reservoirs leads to progressive damage in the central nervous system (CNS). Recent evidence indicates that blood-brain barrier (BBB) pericytes are capable of active HIV-1 infection; however, their latent infection has not been defined. Given their location and function, BBB pericytes are poised to be a key viral reservoir in the development of HAND. We present the first transcriptional analysis of uninfected, active, and latent human BBB pericytes, revealing distinct transcriptional phenotypes. In addition, we demonstrate that latent infection of BBB pericytes relies on AKT signaling for reservoir survival. These findings provide insight into the state of reservoir maintenance in the CNS during HIV-1 infection and provide novel targets for reservoir clearance., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Sleep timing varies between individuals and can be altered in mental and physical health conditions. Sleep and circadian sleep phenotypes, including circadian rhythm sleep-wake disorders, may be driven by endogenous physiological processes, exogeneous environmental light exposure along with social constraints and behavioural factors. Identifying the relative contributions of these driving factors to different phenotypes is essential for the design of personalised interventions. The timing of the human sleep-wake cycle has been modelled as an interaction of a relaxation oscillator (the sleep homeostat), a stable limit cycle oscillator with a near 24-hour period (the circadian process), man-made light exposure and the natural light-dark cycle generated by the Earth's rotation. However, these models have rarely been used to quantitatively describe sleep at the individual level. Here, we present a new Homeostatic-Circadian-Light model (HCL) which is simpler, more transparent and more computationally efficient than other available models and is designed to run using longitudinal sleep and light exposure data from wearable sensors. We carry out a systematic sensitivity analysis for all model parameters and discuss parameter identifiability. We demonstrate that individual sleep phenotypes in each of 34 older participants (65-83y) can be described by feeding individual participant light exposure patterns into the model and fitting two parameters that capture individual average sleep duration and timing. The fitted parameters describe endogenous drivers of sleep phenotypes. We then quantify exogenous drivers using a novel metric which encodes the circadian phase dependence of the response to light. Combining endogenous and exogeneous drivers better explains individual mean mid-sleep (adjusted R-squared 0.64) than either driver on its own (adjusted R-squared 0.08 and 0.17 respectively). Critically, our model and analysis highlights that different people exhibiting the same sleep phenotype may have different driving factors and opens the door to personalised interventions to regularize sleep-wake timing that are readily implementable with current digital health technology., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: DJD and ACS are consultants for F. Hoffmann-La Roche, Ltd., (Copyright: © 2023 Skeldon 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.)

Brain remodeling after an ischemic stroke represents a promising avenue for exploring the cellular mechanisms of endogenous brain repair. A deeper understanding of these mechanisms is crucial for optimizing the safety and efficacy of neuroprotective treatments for stroke patients. Here, we interrogated the role of extracellular vesicles, particularly exosomes, as potential mediators of endogenous repair within the neurovascular unit (NVU). We hypothesized that these extracellular vesicles may play a role in achieving transient stroke neuroprotection. Using the established ischemic stroke model of middle cerebral artery occlusion in adult rats, we detected a surged in the extracellular vesicle marker CD63 in the peri-infarct area that either juxtaposed or co-localized with GFAP-positive glial cells, MAP2-labeled young neurons, and VEGF-marked angiogenic cells. This novel observation that CD63 exosomes spatially and temporally approximated glial activation, neurogenesis, and angiogenesis suggests that extracellular vesicles, especially exosomes, contribute to the endogenous repair of the NVU, warranting exploration of extracellular vesicle-based stroke therapeutics.

Paravalvular leak (PVL), conduction disturbances, and vascular complications remain the most common complications after TAVR. To address these adverse outcomes, the third generation of transcatheter heart valves has been developed. The last generation prosthesis provides an outer pericardial wrap for enhanced sealing and PVL prevention. This study aimed to compare the incidence and severity of PVL and 1-year survival after TAVR using SAPIEN 3 with those using EVOLUT PRO. An observational retrospective analysis was conducted in 1,481 patients who underwent TAVR for symptomatic severe aortic stenosis in 6 different European centers. The primary end point was to assess the frequency and severity of PVL at 30 days after TAVR. The secondary end point was to compare 1-year survival using EVOLUT PRO with that using SAPIEN 3. SAPIEN 3 transcatheter heart valve was implanted in 78.3% of study participants (n = 1,160) whereas EVOLUT PRO was implanted in 21.7% (n = 321). PVL is more commonly observed in patients treated with EVOLUT PRO at prehospital discharge (55.1% vs 37.3%) and at 1-month (51% vs 41.4%) and 1-year (51.3% vs 39.3%) follow-up. This difference mainly concerns low-grade (mild/trace) PVL. The frequency of high-degree (moderate/severe) PVL was almost similar in both groups throughout the study period (5.3% vs 5.8% before hospital discharge, 4% vs 3.1% at 1 month, and 3.2% vs 4.9% at 1 year). No significant difference in survival over 1 year has been observed (hazard ratio 0.73 [0.33 to 1.63], p = 0.442) (Graphical abstract). In conclusion, the detection rate of PVL after TAVR with third-generation heart valves remains high, and there are no major differences between the devices regarding the frequency of significant (moderate/severe) PVL and survival., Competing Interests: Declaration of Competing Interest Dr. Regueiro has served as a proctor for Abbott and Meril Life. Dr. Nombela-Franco has served as a proctor for Abbott and as a consultant for Edwards Lifesciences Inc. and Boston Scientific. Dr. Amat-Santos serves as a proctor for Boston Scientific and Meril Life. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) results from direct penetrating and indirect non-penetrating forces that alters brain functions, affecting millions of individuals annually. Primary injury following TBI is exacerbated by secondary brain injury; foremost is the deleterious inflammatory response. One therapeutic intervention being increasingly explored for TBI is hyperbaric oxygen therapy (HBOT), which is already approved clinically for treating open wounds. HBOT consists of 100% oxygen administration, usually between 1.5 and 3 atm and has been found to increase brain oxygenation levels after hypoxia in addition to decreasing levels of inflammation, apoptosis, intracranial pressure, and edema, reducing subsequent secondary injury. The following review examines recent preclinical and clinical studies on HBOT in the context of TBI with a focus on contributing mechanisms and clinical potential. Several preclinical studies have identified pathways, such as TLR4/NF-kB, that are affected by HBOT and contribute to its therapeutic effect. Thus far, the mechanisms mediating HBOT treatment have yet to be fully elucidated and are of interest to researchers. Nonetheless, multiple clinical studies presented in this review have examined the safety of HBOT and demonstrated the improved neurological function of TBI patients after HBOT, deeming it a promising avenue for treatment.

Purpose: Poor eye-health knowledge and health literacy are pervasive, contributing to worse outcomes. This study aims to examine short- and long-term eye-health knowledge retention following eye-health education interventions in adults., Methods: Vision Detroit was an outreach vision screening program that integrated a 5-Point Teaching Intervention (5PTI), at a Southwest Community Center (SW-CC) from 2015-2017. The 5PTI consists of eye-health learning points developed to verbally educate patients. During vision screenings, eye-health knowledge tests were administered before and after 5PTI (Test 1 and Test 2, respectively). In 2016, Community Eye-Health Education Interventions (CHEI) were initiated at the SW-CC. During CHEI, bilingual healthcare students taught voluntary SW-CC members the 5PTI learning points, regardless of participant interest to attend future screenings. CHEI sessions occurred on separate dates prior to vision screening events. Test 1 and Test 2 scores were compared for all participants. Test 1 scores were compared for those who underwent CHEI prior to vision screening (CHEI positive) versus those who did not (CHEI negative)., Results: Two-hundred-seventeen adult patients met inclusion criteria, with 75.8% women, 82.6% Hispanic, mean age 50.4 ± 16.2 years, 74.6% had high school or less education, and 49.2% had health insurance. Test 1 to Test 2 scores improved after 5PTI (71.2 ± 26.4% vs. 97.2 ± 9.9%, p < .00001). Forty-eight participants attended CHEI and subsequent vision screening. Test 1 scores were higher among those CHEI positive versus CHEI negative (81.1 ± 2.1% vs. 68.3 ± 3.4%, p = .0027)., Conclusion: Simple eye-health education interventions, delivered during vision screenings and via community-based education, can improve eye-health knowledge.

Background: The clinical heterogeneity of chronic rhinosinusitis (CRS) and bronchial asthma is attributable to different underlying inflammatory profiles. However, the similarity between CRS with nasal polyps (CRSwNP) and type-2 asthma pathophysiology speculates that one biological therapy could affect both comorbidities. Despite dupilumab, a monoclonal antibody that targets IL-4α and IL-13 receptors, being used in patients with nasal polyps and severe asthma, real-life data about its efficacy in improving the quality of life and patient symptoms is still lacking. This study's primary objective was to evaluate dupilumab treatment's effect on the frequency of olfactory symptoms and health-related quality of life tests as measured by the Sino-nasal outcome test (SNOT-22) in patients with NP. The secondary objective was the effect of dupilumab on asthma symptom control as measured by the asthma control test (ACT)., Methods: A prospective study was conducted of 166 patients with CRSwNP, with or without asthma. The following variables were collected at baseline and after at least six months of continuous dupilumab therapy; SNOT-22, olfactory symptoms frequency, and ACT score., Results: Asthma prevalence in patients with CRSwNP was high (59.63%), and being female with a history of frequent use of oral corticosteroid (OCS) courses and repeated unsuccessful nasal and para-nasal surgeries for polyposis increased the likelihood of having underlying asthma by 2, 1 and 4 times more, respectively. Additionally, being asthmatic required a longer duration of dupilumab treatment. However, both the health-related quality of life and olfactory symptoms improved equally in both groups., Conclusion: Even with associated comorbid asthma in patients with CRSwNP, treatment with dupilumab could improve the quality of life, olfactory symptoms, and asthma symptom control., (© 2023. The Author(s).)

Introduction: There is a high prevalence of mental health problems among university students. Better prediction and treatment access for this population is needed. In recent years, short-term dynamic factors, which can be assessed using experience sampling methods (ESM), have presented promising results for predicting mental health problems., Methods and Analysis: Undergraduate students from five public universities in Spain are recruited to participate in two web-based surveys (at baseline and at 12-month follow-up). A subgroup of baseline participants is recruited through quota sampling to participate in a 15-day ESM study. The baseline survey collects information regarding distal risk factors, while the ESM study collects short-term dynamic factors such as affect, company or environment. Risk factors will be identified at an individual and population level using logistic regressions and population attributable risk proportions, respectively. Machine learning techniques will be used to develop predictive models for mental health problems. Dynamic structural equation modelling and multilevel mixed-effects models will be considered to develop a series of explanatory models for the occurrence of mental health problems., Ethics and Dissemination: The project complies with national and international regulations, including the Declaration of Helsinki and the Code of Ethics, and has been approved by the IRB Parc de Salut Mar (2020/9198/I) and corresponding IRBs of all participating universities. All respondents are given information regarding access mental health services within their university and region. Individuals with positive responses on suicide items receive a specific alert with indications for consulting with a health professional. Participants are asked to provide informed consent separately for the web-based surveys and for the ESM study. Dissemination of results will include peer-reviewed scientific articles and participation in scientific congresses, reports with recommendations for universities' mental health policy makers, as well as a well-balanced communication strategy to the general public., Study Registration: osf.io/p7csq., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Equitable access to coronavirus 2019 (COVID-19) screening is important to reduce transmission and maintain in-person learning for middle school communities, particularly in disadvantaged schools. Rapid antigen testing, and at-home testing in particular, could offer substantial advantages over onsite testing from a school district's perspective, but it is unknown if engagement in at-home testing can be initiated and sustained. We hypothesized that an at-home COVID-19 school testing program would be noninferior to an onsite school COVID-19 testing program with regard to school participation rates and adherence to a weekly screening testing schedule., Methods: We enrolled 3 middle schools within a large, predominantly Latinx-serving, independent school district into a noninferiority trial from October 2021 to March 2022. Two schools were randomized to onsite and 1 school to at-home COVID-19 testing programs. All students and staff were eligible to participate., Results: Over the 21-week trial, at-home weekly screening testing participation rates were not inferior to onsite testing. Similarly, adherence to the weekly testing schedule was not inferior in the at-home arm. Participants in the at-home testing arm were able to test more consistently during and before returning from school breaks than those in the onsite arm., Conclusions: Results support the noninferiority of at-home testing versus onsite testing both in terms of participation in testing and adherence to weekly testing. Implementation of at-home COVID-19 screening testing should be part of schools' routine COVID-19 prevention efforts nationwide; however, adequate support is essential to ensure participation and persistence in regular at-home testing., (Copyright © 2023 by the American Academy of Pediatrics.)

Objective: To understand the attitudes towards COVID-19 vaccination and trusted sources of vaccination-related information among persons incarcerated in the Federal Bureau of Prisons., Methods: From June-July 2021, persons incarcerated across 122 facilities operated by the Federal Bureau of Prisons were invited to participate in a survey asking their reasons for receiving or declining COVID-19 vaccination and the information sources they relied upon to make these decisions. Descriptive analyses were conducted., Results: A total of 130,789 incarcerated persons with known vaccination status were invited to participate in the survey. At the time of survey, 78,496 (62%) were fully vaccinated; 3,128 (3%) were partially vaccinated and scheduled to complete their second dose, and 44,394 (35%) had declined either a first or second dose. 7,474 (9.5%) of the fully vaccinated group and 2,302 (4.4%) of the group declining either a first or second dose chose to participate in the survey; an overall survey return rate of 7.6% (n = 9,905). Among vaccinated respondents, the most common reason given for accepting vaccination was to protect their health (n = 5,689; 76.1%). Individuals who declined vaccination cited concerns about vaccine side effects (n = 1,304; 56.6%), mistrust of the vaccine (n = 1,256; 54.6%), and vaccine safety concerns (n = 1,252; 54.4%). Among those who declined, 21.2% (n = 489) reported that they would choose to be vaccinated if the vaccine was offered again. Those who declined also reported that additional information from outside organizations (n = 1128; 49.0%), receiving information regarding vaccine safety (n = 841; 36.5%), and/or speaking with a trusted medical advisor (n = 565; 24.5%) may influence their decision to be vaccinated in the future., Conclusion: As the COVID-19 pandemic continues, it is important to increase vaccine confidence in prisons, jails, and detention facilities to reduce transmission and severe health outcomes. These survey findings can inform the design of potential interventions to increase COVID-19 vaccine uptake in these settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Aims/hypothesis: Insulitis is not present in all islets, and it is elusive in humans. Although earlier studies focused on islets that fulfilled certain criteria (e.g. ≥15 CD45 + cells or ≥6 CD3 + cells), there is a fundamental lack of understanding of the infiltration dynamics in terms of its magnitude (i.e. how much) and extent (i.e. where). Here, we aimed to perform an in-depth characterisation of T cell infiltration by investigating islets with moderate (1-5 CD3 + cells) and high (≥6 CD3 + cells) infiltration in individuals with and without type 1 diabetes., Methods: Pancreatic tissue sections from 15 non-diabetic, eight double autoantibody-positive and ten type 1 diabetic (0-2 years of disease duration) organ donors were obtained from the Network for Pancreatic Organ Donors with Diabetes, and stained for insulin, glucagon, CD3 and CD8 by immunofluorescence. T cell infiltration was quantified in a total of 8661 islets using the software QuPath. The percentage of infiltrated islets and islet T cell density were calculated. To help standardise the analysis of T cell infiltration, we used cell density data to develop a new T cell density threshold capable of differentiating non-diabetic and type 1 diabetic donors., Results: Our analysis revealed that 17.1% of islets in non-diabetic donors, 33% of islets in autoantibody-positive and 32.5% of islets in type 1 diabetic donors were infiltrated by 1 to 5 CD3 + cells. Islets infiltrated by ≥6 CD3 + cells were rare in non-diabetic donors (0.4%) but could be found in autoantibody-positive (4.5%) and type 1 diabetic donors (8.2%). CD8 + and CD8 - populations followed similar patterns. Likewise, T cell density was significantly higher in the islets of autoantibody-positive donors (55.4 CD3 + cells/mm 2 ) and type 1 diabetic donors (74.8 CD3 + cells/mm 2 ) compared with non-diabetic individuals (17.3 CD3 + cells/mm 2 ), which was accompanied by higher exocrine T cell density in type 1 diabetic individuals. Furthermore, we showed that the analysis of a minimum of 30 islets and the use of a reference mean value for T cell density of 30 CD3 + cells/mm 2 (the 30-30 rule) can differentiate between non-diabetic and type 1 diabetic donors with high specificity and sensitivity. In addition, it can classify autoantibody-positive individuals as non-diabetic or type 1 diabetic-like., Conclusions/interpretation: Our data indicates that the proportion of infiltrated islets and T cell density change dramatically during the course of type 1 diabetes, and these changes can be already observed in double autoantibody-positive individuals. This suggests that, as disease progresses, T cell infiltration extends throughout the pancreas, reaching the islets and exocrine compartment. While it predominantly targets insulin-containing islets, large accumulations of cells are rare. Our study fulfils the need to further understand T cell infiltration, not only after diagnosis but also in individuals with diabetes-related autoantibodies. Furthermore, the development and application of new analytical tools based on T cell infiltration, like the 30-30 rule, will allow us to correlate islet infiltration with demographic and clinical variables with the aim of identifying individuals at the very early stages of the disease., (© 2023. The Author(s).)

Background: Cardiac amyloidosis is caused by abnormal extracellular deposition of insoluble fibrils in cardiac tissue. It can be fatal when untreated and is often underdiagnosed. Understanding the ethnic/racial differences in risk factors is critical for early diagnosis and treatment to improve clinical outcomes., Methods: We performed a retrospective cross-sectional study utilizing the National Inpatient Sample database from 2015 to 2018 using ICD-10-CM codes. The primary variables of interest were race/ethnicity and amyloidosis subtypes, while the primary outcomes were in-hospital mortality, gastrointestinal bleeding, renal failure, and hospital length-of-stay., Results: Amyloidosis was reported in 0.17% of all hospitalizations (N  =  19,678,415). Of these, 0.09% were non-Hispanic whites, 0.04% were non-Hispanic blacks, and 0.02% were Hispanic. Hospitalizations with ATTR amyloidosis subtype were frequently observed in older individuals and males with coronary artery disease, whereas AL amyloidosis subtype was associated with non-Hispanic whites, congestive heart failure, and longer hospital length of stay. Renal failure was associated with non-Hispanic blacks (adjusted relative risk [RR]  =  1.31, p < 0.001), Hispanics (RR  =  1.08, p  =  0.028) and had an increased risk of mortality. Similarly, the hospital length of stay was longer with non-Hispanic blacks (RR  =  1.19, p < 0.001) and Hispanics (RR  =  1.05, p  =  0.03) compared to non-Hispanic whites. Hispanics had a reduced risk of mortality (RR  =  0.77, p  =  0.028) compared to non-Hispanic whites and non-Hispanic blacks, and no significant difference in mortality was seen between non-Hispanic whites and non-Hispanic blacks (RR  =  1.00, p  =  0.963)., Conclusions: Our findings highlight significant ethnic/racial differences in risk factors and outcomes among amyloidosis-related US hospitalizations that can possibly be used for early detection, treatment, and better clinical outcomes., Competing Interests: Conflict of Interest Statement/Disclosures The authors have no financial or other conflicts of interest to disclose., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Renal hyperfiltration (RHF) is a prevalent phenomenon in critically ill patients characterized by augmented renal clearance (ARC) and increased of elimination of renally eliminated medications. Multiple risk factors had been described and potential mechanisms may contribute to the occurrence of this condition. RHF and ARC are associated with the risk of suboptimal exposure to antibiotics increasing the risk of treatment failure and unfavorable patient outcomes. The current review discusses the available evidence related to the RHF phenomenon, including definition, epidemiology, risk factors, pathophysiology, pharmacokinetic variability, and considerations for optimizing the dosage of antibiotics in critically ill patients., Competing Interests: The authors declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article., (Copyright © 2023 Jorge Rico-Fontalvo et al.)

Background: Data are scarce on differences in the rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection after the first infection., Aims: We examined nationwide data on SARS-CoV-2 reinfection in Kuwait according to four-time windows to reinfection: 29-45 days, 46-60 days, 61-90 days, and ≥ 91 days., Methods: This was a population-level retrospective cohort study conducted between 31 March 2020 and 31 March 2021. We reviewed evidence of second positive RT-PCR test results for those who had previously recovered from COVID-19 and tested negative., Results: Reinfection rates were: 0.52% for reinfection window 29-45 days, 0.36% for 45-60 days, 0.29% for 61-90 days, and 0.20% for ≥ 91 days. The mean age (standard deviation [SD]) of individuals with the shortest reinfection time interval (29-45 days) was significantly older than the mean age of all other groups - 43.3 years (SD 17.5) compared with: 39.0 years (SD 16.5), P = 0.037 for 46-60-day interval; 38.3 years (SD 16.5), P = 0.002 for 61-90-day interval; and 39.2 years (SD 14.4), P = 0.001 for ≥ 91-days interval., Conclusion: SARS-CoV-2 reinfection was uncommon among this adult population. Older age was associated with a shorter time to reinfection., (Copyright © Authors 2023; Licensee: World Health Organization. EMHJ is an open access journal. This paper is available under the Creative Commons Attribution Non-Commercial ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Background: In hospitalized patients with COVID-19, acute kidney injury (AKI) is associated with higher mortality, but data are lacking on healthcare resource utilization (HRU) and costs related to AKI, community-acquired AKI (CA-AKI), and hospital-acquired AKI (HA-AKI). Objectives: To quantify the burden of AKI, CA-AKI, and HA-AKI among inpatients with COVID-19. Methods: This retrospective cohort study included inpatients with COVID-19 discharged from US hospitals in the Premier PINC AI™ Healthcare Database April 1-October 31, 2020, categorized as AKI, CA-AKI, HA-AKI, or no AKI by ICD-10-CM diagnosis codes. Outcomes were assessed during index (initial) hospitalization and 30 days postdischarge. Results: Among 208 583 COVID-19 inpatients, 30%, 25%, and 5% had AKI, CA-AKI, and HA-AKI, of whom 10%, 7%, and 23% received dialysis, respectively. Excess mortality, HRU, and costs were greater for HA-AKI than CA-AKI. In adjusted models, for patients with AKI vs no AKI and HA-AKI vs CA-AKI, odds ratios (ORs) (95% CI) were 3.70 (3.61-3.79) and 4.11 (3.92-4.31) for intensive care unit use and 3.52 (3.41-3.63) and 2.64 (2.52-2.78) for in-hospital mortality; mean length of stay (LOS) differences and LOS ratios (95% CI) were 1.8 days and 1.24 (1.23-1.25) and 5.1 days and 1.57 (1.54-1.59); and mean cost differences and cost ratios were $7163 and 1.35 (1.34-1.36) and $19 127 and 1.78 (1.75-1.81) (all P  < .001). During the 30 days postdischarge, readmission LOS was ≥6% longer for AKI vs no AKI and HA-AKI vs CA-AKI; outpatient costs were ≥41% higher for HA-AKI vs CA-AKI or no AKI. Only 30-day new dialysis (among patients without index hospitalization dialysis) had similar odds for HA-AKI vs CA-AKI (2.37-2.8 times higher for AKI, HA-AKI, or CA-AKI vs no AKI). Discussion: Among inpatients with COVID-19, HA-AKI had higher excess mortality, HRU, and costs than CA-AKI. Other studies suggest that interventions to prevent HA-AKI could decrease excess morbidity, HRU, and costs among inpatients with COVID-19. Conclusions: In adjusted models among COVID-19 inpatients, AKI, especially HA-AKI, was associated with significantly higher mortality, HRU, and costs during index admission, and higher dialysis and longer readmission LOS during the 30 days postdischarge. These findings support implementation of interventions to prevent HA-AKI in COVID-19 patients., Competing Interests: R.H.M., N.A.R., and L.A.C. are full-time employees of Premier, Inc., which received payment from bioMerieux to conduct the study, and have no competing interests with respect to the study. R.H.M., N.A.R., and L.A.C. had access to the study data. J.T., P.M., J.P.K., A.S., and T.R. are full-time employees of bioMerieux, Inc., and P.M. and J.P.K. are inventors on patents assigned to bioMerieux and own shares in bioMerieux. J.L.K. reports consulting fees and research support from Astute-bioMerieux, Fresenius Medical, Mallinckrodt, Novartis, Guard Therapeutics, and the NIH and speakers bureau fees from NXStage Medical. The authors report no other conflicts of interest with this work.

Background: Statin therapy is recommended for people with type 2 diabetes (T2D) to lower cardiovascular risk; however, evidence suggests that significant gaps in statin therapy exist., Objective: To evaluate (1) the impact of a community pharmacist-led model for initiating statin therapy in people with type 2 diabetes (T2D) on statin initiation and (2) pharmacists' self-reported perceptions of the intervention feasibility and fidelity to the intervention., Methods: This was a type 1 hybrid effectiveness-implementation study of 9 intervention and 18 control pharmacies within a community pharmacy chain. Pharmacy staff proactively identified patients with T2D not taking a statin and prescribed a statin via a collaborative practice agreement or facilitated acquisition of a prescription from the patient's preferred prescriber. The eligible population included patients aged 18-84 years with T2D, who had filled ≥60 days' supply of one, noninsulin, diabetes medication in a rolling 6-month period, and who had not filled a statin during the same period. A Cox proportional hazards model was used to compare time to statin initiation. Pharmacists at intervention pharmacies completed a survey at 6 and 12 months after implementation (March and August 2019, respectively) to assess intervention feasibility and fidelity., Results: For the statin initiation analysis, 1670 intervention patients were matched to 3358 control patients. Overall, 26.3% (n=442) of intervention patients and 25.4% (n=854) of control patients initiated a statin within 12 months of their index date. There was no difference in statin initiation likelihood between intervention and control patients (hazard ratio: 1.00; 95% CI: 0.83, 1.21). Fifteen pharmacists completed the 6-month survey (33% response rate), and 12 completed the 12-month survey (26%). The intervention's feasibility score was 4.0 at 6 months and 4.2 at 12 months, indicating an increase in perceived feasibility. Fidelity decreased from 6 to 12 months., Conclusion: The community pharmacist-led intervention resulted in more patients initiating statin therapy as compared to usual care; however, the differences were not statistically significant. Pharmacists perceived the intervention to be feasible; however, fidelity decreased over time., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Some reports have discussed the development of a new entity called vaccine-induced immune thrombotic thrombocytopenia after COVID-19 vaccination. In this case series, we are describing four patients who have developed lupus anticoagulant-associated venous thromboembolism after Pfizer mRNA COVID-19 vaccination. All were COVID-19 negative on admission. Three had developed thrombosis after the first dose and one after the second dose of vaccination. All of them had venous thrombosis. Three patients developed thrombosis 2 weeks after vaccination and the fourth patient had developed thrombosis after 3 weeks of vaccination. None of the patients had thrombocytopenia on or during admission as seen in the case of vaccine-induced immune thrombotic thrombocytopenia. All patients had positive lupus anticoagulant and negative anticardiolipin antibodies and antibeta2 glycoprotein I. All of them were stable on discharge and were treated with low molecular weight heparin followed by warfarin. We suggest the presence of a possible link between the development of antiphospholipid antibodies and COVID-19 vaccine that requires further assessment., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Prevalence of Parkinson's Disease (PD) in the Philippines has been estimated to be < 1 % based on a 2007 nationwide survey conducted by the Philippine Neurological Association, but without case ascertainment. Since there is still paucity of data, we aim to determine the prevalence of PD in a rural community and the possible predisposing factors on the development of the disease., Methods: This is a two-phase descriptive study which investigated the prevalence of PD and associated risk factors in a randomly selected rural community in Candelaria, Quezon Province. A validated screening questionnaire was utilized, and case ascertainment was done in eligible respondents., Results: A total of 365 respondents aged ≥ 20 years were randomly surveyed from 2016 to 2017. Two cases of PD aged ≥ 60 years were reported. Thus, the prevalence of PD in the community was 0.55 %. Age-specific prevalence of PD among individuals ≥ 60 years was 4.35 %.Insecticide use was infrequent in the community and was recorded in one PD patient. Protective factors like smoking and drinking tea were not observed in both cases whereas coffee intake was reported in one PD patient., Conclusion: This community-based epidemiologic study on PD is consistent with a nationwide study. The study portrayed certain demographic and environmental features inherent in a community, which are potential confounding variables in PD development. Future larger population studies be recommended to establish PD in the advancing age and to further support the link of various factors with PD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

A GGGGCC 24+ hexanucleotide repeat expansion (HRE) in the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), fatal neurodegenerative diseases with no cure or approved treatments that substantially slow disease progression or extend survival. Mechanistic underpinnings of neuronal death include C9ORF72 haploinsufficiency, sequestration of RNA-binding proteins in the nucleus, and production of dipeptide repeat proteins. Here, we used an adeno-associated viral vector system to deliver CRISPR/Cas9 gene-editing machineries to effectuate the removal of the HRE from the C9ORF72 genomic locus. We demonstrate successful excision of the HRE in primary cortical neurons and brains of three mouse models containing the expansion (500-600 repeats) as well as in patient-derived iPSC motor neurons and brain organoids (450 repeats). This resulted in a reduction of RNA foci, poly-dipeptides and haploinsufficiency, major hallmarks of C9-ALS/FTD, making this a promising therapeutic approach to these diseases., (© 2022. The Author(s).)

Mitochondrial dysfunction has been reported in chronic obstructive pulmonary disease (COPD). Transfer of mitochondria from mesenchymal stem cells to airway smooth muscle cells (ASMCs) can attenuate oxidative stress-induced mitochondrial damage. It is not known whether mitochondrial transfer can occur between structural cells in the lungs or what role this may have in modulating bioenergetics and cellular function in healthy and COPD airways. Here, we show that ASMCs from both healthy ex-smokers and subjects with COPD can exchange mitochondria, a process that happens, at least partly, via extracellular vesicles. Exposure to cigarette smoke induces mitochondrial dysfunction and leads to an increase in the donation of mitochondria by ASMCs, suggesting that the latter may be a stress response mechanism. Healthy ex-smoker ASMCs that receive mitochondria show increases in mitochondrial biogenesis and respiration and a reduction in cell proliferation, irrespective of whether the mitochondria are transferred from healthy ex-smoker or COPD ASMCs. Our data indicate that mitochondrial transfer between structural cells is a homeostatic mechanism for the regulation of bioenergetics and cellular function within the airways and may represent an endogenous mechanism for reversing the functional consequences of mitochondrial dysfunction in diseases such as COPD.

Background: Body weight changes occur frequently during advanced stages of Spinocerebellar Ataxia type 2 (SCA2), nevertheless limited information exists on biomarkers of nutritional status of these patients., Objective.: To assess changes in surrogate nutritional markers of SCA2 patients; to explore their associations with expanded CAG repeats and disease severity., Methods: One-hundred-thirteen SCA2 patients and 50 healthy controls underwent a comprehensive anthropometrical and biochemical assessment protocol of the nutritional status. Neurological and genotype assessments were also performed., Results: A decrease in weight, body mass index (BMI), cutaneous skinfold thickness, fat mass, arm muscle circumference, calf circumference and skeletal muscle mass was observed in SCA2 patients compared to the controls. The total/HDL cholesterol ratio was significantly reduced in patients. BMI was correlated with the age at onset. Overall, anthropometric measures were correlated with clinical markers of disease severity and were more evident in severe and moderate cases., Conclusions: Using anthropometric measures in the assessment of the nutritional status of SCA2 patients might provide hints about pathophysiological mechanisms that underlie metabolic abnormalities in SCA2. Anthropometric are close related with disease severity and progression, and trigger preventive therapies aimed to ameliorate weight loss and wasting in these patients.

The COVID-19 pandemic has affected millions of people, including hundreds of deaths. The search for adequate treatments and interventions that influence poor prognostic factors and reduce mortality has led to excessive use of antibiotics based on the possible existence of bacterial co-infection. However, there is no evidence to justify the systematic use of antimicrobials in COVID-19. The recommendations seek to provide knowledge regarding treatment; standardizing a management algorithm requires validation in clinical trials and studies of greater methodological rigor., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Dueñas-Castell et al.)

Background: Several pieces of evidence have shown the neurotrophic effect of erythropoietin (EPO) and its introduction in the therapeutic practice of neurological diseases. However, its usefulness in the treatment of spinocerebellar ataxia type 2 (SCA2) has not been proven despite the fact that it is endogenously reduced in these patients., Objective: The study aims to investigate the safety, tolerability, and clinical effects of a nasally administered recombinant EPO in SCA2 patients., Methods: Thirty-four patients were enrolled in this double-blind, randomized, placebo-controlled, phase I-II clinical trial of the nasally administered human-recombinant EPO (NeuroEPO) for 6 months. The primary outcome was the change in the spinocerebellar ataxia functional index (SCAFI), while other motor, neuropsychological, and oculomotor measures were assessed., Results: The 6-month changes in SCAFI score were slightly higher in the patients allocated to NeuroEPO treatment than placebo in spite of the important placebo effect observed for this parameter. However, saccade latency was significantly decreased in the NeuroEPO group but not in placebo. The frequency and severity of adverse events were similar between both groups, without evidences of hematopoietic activity of the drug., Conclusions: This study demonstrated the safety and tolerability of NeuroEPO in SCA2 patients after 6 months of treatments and suggested a small clinical effect of this drug on motor and cognitive abnormalities, but confirmatory studies are warranted. © 2022 International Parkinson and Movement Disorder Society., (© 2022 International Parkinson and Movement Disorder Society.)

Aptamers have been the subject of more than 144 000 papers to date. However, there has been a growing concern that discrepancies in the reporting of aptamer research limit the reliability of these reagents for research and other applications. These observations noting inconsistencies in the use of our RNA antilysozyme aptamer served as an impetus for our systematic review of the reporting of aptamer sequences in the literature. Our detailed examination of the literature citing the RNA antilysozyme aptamer revealed that 93% of the 61 publications reviewed reported unexplained altered sequences with 96% of those using DNA variants. The 10 most cited aptamers were examined using a standardized methodology in order to categorize the extent to which the sequences themselves and altered sequences were adequately described in the literature. Our review of 780 aptamer publications spanned decades, multiple journals, and research groups and revealed that 41% of the papers reported unexplained sequence alterations or omitted sequences. We identified 10 common categories of sequence alterations including deletions, substitutions, and additions, among others. Overall, our findings can be used as a starting point for building better practices in author submissions and publication standards, elevating the rigor and reproducibility of aptamer research.

Base editors (BEs) have opened new avenues for the treatment of genetic diseases. However, advances in delivery approaches are needed to enable disease targeting of a broad range of tissues and cell types. Adeno-associated virus (AAV) vectors remain one of the most promising delivery vehicles for gene therapies. Currently, most BE/guide combinations and their promoters exceed the packaging limit (∼5 kb) of AAVs. Dual-AAV delivery strategies often require high viral doses that impose safety concerns. In this study, we engineered an adenine base editor (ABE) using a compact Cas9 from Neisseria meningitidis (Nme2Cas9). Compared with the well-characterized Streptococcus pyogenes Cas9-containing ABEs, ABEs using Nme2Cas9 (Nme2-ABE) possess a distinct protospacer adjacent motif (N 4 CC) and editing window, exhibit fewer off-target effects, and can efficiently install therapeutically relevant mutations in both human and mouse genomes. Importantly, we show that in vivo delivery of Nme2-ABE and its guide RNA by a single AAV vector can efficiently edit mouse genomic loci and revert the disease mutation and phenotype in an adult mouse model of tyrosinemia. We anticipate that Nme2-ABE, by virtue of its compact size and broad targeting range, will enable a range of therapeutic applications with improved safety and efficacy due in part to packaging in a single-vector system., Competing Interests: H.Z., N.B., P.L., X.D.G., S.A.W., W.X., and E.J.S. are coinventors on patent filings related to this study. G.G. is scientific cofounder, scientific advisor, and equity holder of Voyager Therapeutics, Adrenas Therapeutics, and Aspa Therapeutics. E.J.S. is a cofounder, scientific advisor, and equity holder of Intellia Therapeutics, and a member of the scientific advisory board of Tessera Therapeutics., (Copyright 2022, Mary Ann Liebert, Inc., publishers.)

The emotional and psychological toll of the COVID-19 pandemic has been characterized as a parallel pandemic, disproportionately affecting health care workers when compared to the general population. Recognizing the tragic effects that the pandemic was having on the psyche of our health care workers, a multidisciplinary peer-support program called Helping Healers Heal was augmented to address these complex needs in a large, urban, academic medical center in the Bronx, NY. A multimodal approach including wellness events, emotional support rounds, fast-tracked connections with therapeutic support, and coalition building was used to reach 80% of staff from May through August, 2020. The multidisciplinary team planned events and interventions to appeal to the myriad ways people cope and build resilience, and by utilizing existing resources, it proved extremely cost-effective. In a survey of the program's participants, 94% of respondents "agreed" or "strongly agreed" that their participation helped alleviate stress., (Copyright © 2021 the American College of Medical Quality.)

Methicillin-resistant Staphylococcus (MRS) is a leading cause of skin and soft tissue infections in companion animals, with limited treatment options available due to the frequent cross-resistance of MRS to other antibiotics. In this study, we report the prevalence, species distribution, genetic diversity, resistance mechanism and cross-resistance patterns of MRS isolated from companion animal (mostly dog and cat) clinical cases submitted to Iowa State University Veterinary Diagnostic Laboratory (ISU VDL) between 2012 and 2019. The majority of isolates were identified as Staphylococcus pseudintermedius (68.3%; 2379/3482) and coagulase-negative Staphylococcus (CoNS) (24.6%; 857/3482), of which 23.9% and 40.5% were phenotypically resistant to methicillin, respectively. Cross resistance to other β-lactams (and to a lesser extent to non-β-lactams) was common in both methicillin-resistant S. pseudintermedius (MRSP) and CoNS (MRCoNS), especially when oxacillin MIC was ≥4 μg/mL (vs. ≥0.5−<4 μg/mL). The PBP2a protein was detected by agglutination in 94.6% (521/551) MRSP and 64.3% (146/227) MRCoNS. A further analysis of 31 PBP2a-negative MRS isolates (all but one MRCoNS) indicated that 11 were mecA gene-positive while 20 were negative for mecA and other mec genes by PCR. The resistance to last-resort anti-staphylococcal human drugs (e.g., tigecycline, linezolid, vancomycin) among the MRS tested was none to very low. Even though genotyping indicated an overall high level of genetic diversity (87 unique PFGE patterns and 20 MLST types) among a subset of MRSP isolates tested (n = 106), certain genotypes were detected from epidemiologically connected cases at the same or different time points, suggesting persistence and/or nosocomial transmission. These results indicate a relatively high prevalence of MRS from companion animals in the Midwestern US; therefore, it is important to perform routine susceptibility testing of Staphylococcus in veterinary clinical settings for the selection of appropriate antimicrobial therapy.

The mass of the W boson, a mediator of the weak force between elementary particles, is tightly constrained by the symmetries of the standard model of particle physics. The Higgs boson was the last missing component of the model. After observation of the Higgs boson, a measurement of the W boson mass provides a stringent test of the model. We measure the W boson mass, M W , using data corresponding to 8.8 inverse femtobarns of integrated luminosity collected in proton-antiproton collisions at a 1.96 tera-electron volt center-of-mass energy with the CDF II detector at the Fermilab Tevatron collider. A sample of approximately 4 million W boson candidates is used to obtain [Formula: see text] , the precision of which exceeds that of all previous measurements combined (stat, statistical uncertainty; syst, systematic uncertainty; MeV, mega-electron volts; c , speed of light in a vacuum). This measurement is in significant tension with the standard model expectation.

There is considerable evidence that patients with inflammatory conditions are at higher risk of developing cardiovascular (CV) disease including carotid artery stenosis. CV disease accounts for 35-50% of the excess mortality in patients with inflammatory diseases such as rheumatoid arthritis, with cerebrovascular disease being the second leading cause of death. We review current evidence regarding the association of inflammatory conditions and specifically carotid artery disease. Clinical epidemiological observations suggest that mechanisms other than classic risk factors may promote accelerated atherogenesis in rheumatoid and other inflammatory arthritis and carotid artery disease is increased in individuals with these conditions. Additional studies to better understand the underlying mechanisms and targeted strategies to mitigate such risk are indicated. For now, lifestyle modifications, aggressive treatment of risk factors and lipid lowering therapy in appropriate individuals is indicated., Competing Interests: Conflict of Interest None declared for Tayana Rodriguez, Angelical Lehker and Debabrata Mukherjee. Dimitri P Mikhailidis has given talks, acted as a consultant or attended conferences sponsored by Amgen and Novo Nordisk., (Copyright © 2021 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Anorexia nervosa (AN) is a disorder characterized by an incapacitating fear of weight gain and by a disturbance in the way the body is experienced, facets that motivate dangerous weight loss behaviors. Multimodal neuroimaging studies highlight atypical neural activity in brain networks involved in interoceptive awareness and reward processing., Methods: The current study used resting-state neuroimaging to model the architecture of large-scale functional brain networks and characterize network properties of individual brain regions to clinical measures. Resting-state neuroimaging was conducted in 62 adolescents, 22 (21 female) with a history of AN and 40 (39 female) healthy controls (HCs). Sensorimotor and basal ganglia regions, as part of a 165-region whole-brain network, were investigated. Subject-specific functional brain networks were computed to index centrality. A contrast analysis within the general linear model covarying for age was performed. Correlations between network properties and behavioral measures were conducted (significance q < .05)., Results: Compared to HCs, AN had lower connectivity from sensorimotor regions, and greater connectivity from the left caudate nucleus to the right postcentral gyrus. AN demonstrated lower sensorimotor centrality, but higher basal ganglia centrality. Sensorimotor connectivity dyads and centrality exhibited negative correlations with body dissatisfaction and drive for thinness, two essential features of AN., Conclusions: These findings suggest that AN is associated with greater communication from the basal ganglia, and lower information propagation in sensorimotor cortices. This is consistent with the clinical presentation of AN, where individuals exhibit patterns of rigid habitual behavior that is not responsive to bodily needs, and seem "disconnected" from their bodies., (© 2022. The Author(s).)