Rapid resistance profiling of SARS-CoV-2 protease inhibitors.

Resistance to nirmatrelvir (Paxlovid) has been shown by multiple groups and may already exist in clinical SARS-CoV-2 isolates. Here a robust cell-based assay is used to determine the relative potencies of nirmatrelvir, ensitrelvir, and FB2001 against a panel of SARS-CoV-2 main protease (M) variants. The results reveal that these three drugs have at least partly distinct resistance mutation profiles and raise the possibility that the latter compounds may be effective in some instances of Paxlovid resistance and vice versa.

Imaging dose and image quality of kilovoltage imaging implemented on a helical tomotherapy unit.

The purpose of this work was to evaluate the imaging dose for the Accuray Radixact ClearRT system. Low-contrast resolution and CT number consistency was evaluated as well. CTDI measurements were compared to vendor supplied values, and similar measurements were done on a Varian TrueBeam kV cone-beam CT (CBCT) and a Philips Big Bore CT scanner.

The PRO-AGE Tool and Its Association With Post Discharge Outcomes in Older Adults Admitted From the Emergency Department.

Background: Existing risk scores assessing geriatric vulnerability in the emergency department (ED) have shown limited predictive power, especially in diverse populations. We investigated the relationship of a quick and easy-to-administer geriatric vulnerability scoring system with functional decline and mortality in older patients admitted to multiple hospitals through the ED in the United States (US) and Brazil (BR).

Method: Federated, international, multicenter observational study of hospitalized ED patients aged ≥ 65 from US and BR.

Development and validation of machine-learning models for predicting the risk of hypertriglyceridemia in critically ill patients receiving propofol sedation using retrospective data: a protocol.

Introduction: Propofol is a widely used sedative-hypnotic agent for critically ill patients requiring invasive mechanical ventilation (IMV). Despite its clinical benefits, propofol is associated with increased risks of hypertriglyceridemia. Early identification of patients at risk for propofol-associated hypertriglyceridemia is crucial for optimising sedation strategies and preventing adverse outcomes.

Association between resting-state synaptic activity and overall performance in a cognitive visuoconstructive task as revealed by magnetoencephalography (MEG).

Performance of a task involves the engagement of various brain areas, as evidenced by the effects of lesions of particular brain areas and the results of functional neuroimaging and neurophysiological studies. Here we tested the hypothesis that overall task performance would depend on the level of ongoing, resting-state change in synaptic activity of participating areas, such that the degree of success of the outcome would be higher, the higher the resting-state activation. For that purpose, we used 248-sensor magnetoencephalography (MEG) in healthy people to obtain estimates of resting-state synaptic activity in various areas and then correlated those estimates to the average performance score in three visuospatial tasks assessed outside the MEG session using the Montreal Cognitive Assessment (MoCA), namely the Trails, Cube, and Clock Drawing (TCCD) tasks.

Intergenerational Impacts of Historical Trauma on Contemporary Depression Symptoms Among Indigenous Communities.

Introduction: Indigenous communities in the U.S. and Canada have endured generations of historical trauma.

Learning from the roundtable on obesity solutions experiences: A 10-year anniversary point of view.

The Roundtable on Obesity Solutions (ROOS), established in 2014, is a unique organization of multisectoral voices addressing the public health challenge of obesity. The ROOS brings together practitioners, researchers, funders, companies, health systems, government agencies, and the lived experience to dialogue and guide the national conversation about the multilevel challenges and opportunities related to obesity. This paper presents insights and key learnings from a symposium developed to celebrating the 10th Anniversary of the ROOS.

Echocardiogram utilization in hospitalized adults with isolated traumatic brain injury: Propensity-matched analysis of the national inpatient sample 2016-2020.

Background: Early left ventricular systolic dysfunction is common after moderate-severe traumatic brain injury (TBI). Echocardiography (Echo) can evaluate cardiac function across various clinical scenarios; however, its utilization in isolated TBI remains poorly understood. To address this gap, we aim to examine Echo utilization in hospitalized adults with isolated TBI.

Exposed digits increase weight bearing and alter sub-bandage pressures in dogs with forelimb splints.

Objective: The goal of this study was to evaluate the difference in weight bearing in a toes-in splint versus a toes-out forelimb splint and to determine the difference in sub-bandage pressures between the groups. We hypothesized that (1) weight bearing would not be different between the 2 splints and that (2) sub-bandage pressures would be distributed higher on the distal digits in the toes-out splint and pressures would be more evenly distributed across the paw in the toes-in splint.

Methods: In this controlled crossover trial, a random forelimb of 10 healthy dogs was bandaged with a splint that left the digits exposed and again with a splint that encompassed the digits.

Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: ASCO Guideline Update.

Purpose: To provide updated guidance regarding neoadjuvant chemotherapy (NACT) and primary cytoreductive surgery (PCS) among patients with stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer (epithelial ovarian cancer [EOC]).

Methods: A multidisciplinary Expert Panel convened and updated the systematic review.

Results: Sixty-one studies form the evidence base.

New Directions For Women's Health: Expanding Understanding, Improving Research, Addressing Workforce Limitations.

In the United States, the field of women's health faces critical challenges. This article, part of the National Academy of Medicine's Vital Directions for Health and Health Care: Priorities for 2025 initiative, emphasizes the need for a holistic, lifespan approach to women's health that considers biological sex, gender, and intersecting social factors. We identify three key challenges: broadening the understanding of women's health beyond reproductive issues, improving the research ecosystem, and addressing workforce limitations.

Diagnosis of atrial cardiomyopathy: from the electrocardiogram to the new opportunities with multimodality imaging.

Atrial cardiomyopathy (AC) has been defined by the European Heart Rhythm Association as "Any complex of structural, architectural, contractile, or electrophysiologic changes in the atria with the potential to produce clinically relevant manifestations".1 The left atrium (LA) plays a key role in maintaining normal cardiac function; in fact atrial dysfunction has emerged as an essential determinant of outcomes in different clinical scenarios, such as valvular diseases, heart failure (HF), coronary artery disease (CAD) and atrial fibrillation (AF). A comprehensive evaluation, both anatomical and functional, is routinely performed in cardiac imaging laboratories.

Exploring Glypican-3 targeted CAR-NK treatment and potential therapy resistance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and the second leading cause of cancer-related mortality globally. Despite advancements in current HCC treatment, it remains a malignancy with poor prognosis. Therefore, developing novel treatment options for patients with HCC is urgently needed.

Constructs across a hierarchical, dimensional model of psychopathology show differential associations with social and general cognitive ability.

Many psychiatric disorders and associated psychopathology dimensions are related to social cognitive deficits and reduced general cognitive ability. The current study applied a hierarchical, dimensional approach to better understand associations among psychopathology, social cognition, and general cognitive ability. Data were collected from two samples (n = 653), including psychosis-spectrum patients, their first-degree relatives, and individuals from community sources.

The Kinesin Kar3 is Required for Endoplasmic Reticulum-Associated Degradation.

Degradation of aberrant, excess, and regulatory proteins at the endoplasmic reticulum (ER) is a conserved feature of eukaryotic cells, disruption of which contributes to disease. While remarkable progress has been made in recent years, mechanisms and genetic requirements for ER-Associated Degradation (ERAD) remain incompletely understood. We recently conducted a screen for genes required for turnover of a model ER translocon-associated substrate of the Hrd1 ubiquitin ligase in .

Supine Blood Pressure and Risk of Cardiovascular Disease and Mortality.

Importance: Nocturnal hypertension while asleep is associated with substantial increases in risk of cardiovascular disease (CVD) and death. Whether hypertension while supine is a risk factor associated with CVD independent of seated hypertension remains unknown.

Objective: To investigate the association between supine hypertension and CVD outcomes and by hypertension treatment status.

Oral vs Intravenous Antibiotics for Fracture-Related Infections: The POvIV Randomized Clinical Trial.

Importance: Fracture-related infection (FRI) is a serious complication following fracture fixation surgery. Current treatment of FRIs entails debridement and 6 weeks of intravenous (IV) antibiotics. Lab data and retrospective clinical studies support use of oral antibiotics, which are less expensive and may have fewer complications than IV antibiotics.

Association between Sex Hormones and Mood, Cravings and Urges in Males and Females Who Smoke Tobacco.

Background: Mood influences smoking behavior, with sex and sex hormones potentially complicating these relationships. We explored associations between Profile of Mood States (POMS) and Questionnaire on Smoking Urges (QSU) - Brief with sex hormones in men and women who smoke.

Methods: This is a secondary analysis of treatment non-responders from a smoking cessation randomized trial investigating exogenous progesterone's efficacy.

A Lack of Joint Line Tenderness Is Consistent With a Healed Meniscus, But Positive Clinical Examination Findings and MRI Scans Are Inconsistent in Identifying Failure After Meniscal Repair: A Systematic Review and Subgroup Meta-analysis.

Background: The number of meniscal repairs being completed each year is increasing; however, the optimal, cost-effective postoperative assessment to determine the success or failure of a meniscal repair is not well known.

Purpose/hypothesis: The purpose of this systematic review was to identify the clinical examination testing that correlates with objective magnetic resonance imaging (MRI) or second-look arthroscopy (SLA) findings to determine an optimal clinical workup for assessing postoperative meniscal repair healing. It was hypothesized that specific clinical tests would correlate with meniscal repairs that did not heal.

Evaluation of antimicrobial susceptibility testing methods for complex isolates from people with and without cystic fibrosis.

The complex (BCC) is a group of Gram-negative bacteria that cause opportunistic infections, most notably in people with cystic fibrosis (CF), and have been associated with outbreaks caused by contaminated medical products. Antimicrobial susceptibility testing (AST) is often used to guide treatment for BCC infections, perhaps most importantly in people with CF who are being considered for lung transplant. However, recent studies have highlighted problems with AST methods.