A high polygenic risk score is associated with SSA/SSB antibody positivity and early onset in primary Sjögren's disease.

Objectives: To calculate a polygenic risk score (PRS) based on single nucleotide variants (SNVs) previously associated with primary Sjögren's disease (SjD) with genome-wide significance, and determine the genetic risk for SjD stratified by antibodies, sex and age at diagnosis.

Methods: Patients with SjD (n = 1065) were genotyped using Illumina OmniExpressExome chip. Control genotype data were available (n = 7742).

Associations of Muscle-Strengthening Activity and Cognitive Function in Community-Dwelling Middle-Aged and Older Adults.

Objective: To determine the associations between muscle-strengthening activity (MSA) and cognitive function among middle-aged and older adults.

Methods: This cross-sectional study included 2973 participants aged ≥55 in the Cooper Center Longitudinal Study. Participants self-reported leisure-time physical activity.

Glucose-sensitive insulin with attenuation of hypoglycaemia.

The risk of inducing hypoglycaemia (low blood glucose) constitutes the main challenge associated with insulin therapy for diabetes. Insulin doses must be adjusted to ensure that blood glucose values are within the normal range, but matching insulin doses to fluctuating glucose levels is difficult because even a slightly higher insulin dose than needed can lead to a hypoglycaemic incidence, which can be anything from uncomfortable to life-threatening. It has therefore been a long-standing goal to engineer a glucose-sensitive insulin that can auto-adjust its bioactivity in a reversible manner according to ambient glucose levels to ultimately achieve better glycaemic control while lowering the risk of hypoglycaemia.

Longitudinal Associations of Aerobic Activity, Muscle-Strengthening Activity, and Adiposity with Cardiorespiratory Fitness.

Purpose: Cardiorespiratory fitness (CRF) declines with age, and greater declines increase the risk for adverse health outcomes. Understanding factors that attenuate age-related decreases in CRF can help extend healthy life. We sought to determine the longitudinal associations of aerobic physical activity, muscle-strengthening activity (MSA), and adiposity with CRF.

Dietary patterns and cardiorespiratory fitness in midlife and subsequent all-cause dementia: findings from the cooper center longitudinal study.

Background: Identifying lifestyle factors that independently or jointly lower dementia risk is a public health priority given the limited treatment options available to patients. In this cohort study, we examined the associations between Mediterranean or Dietary Approaches to Stop Hypertension (DASH) diet adherence and cardiorespiratory fitness (CRF) with later-life dementia, and assessed whether the associations between dietary pattern and dementia are modified by CRF.

Methods: Data are from 9,095 adults seeking preventive care at the Cooper Clinic (1987-1999) who completed a 3-day dietary record and a maximal exercise test.

Dynamic gating of perceptual flexibility by non-classically responsive cortical neurons.

The ability to flexibly respond to sensory cues in dynamic environments is essential to adaptive auditory-guided behaviors. Cortical spiking responses during behavior are highly diverse, ranging from reliable trial-averaged responses to seemingly random firing patterns. While the reliable responses of 'classically responsive' cells have been extensively studied for decades, the contribution of irregular spiking 'non-classically responsive' cells to behavior has remained underexplored despite their prevalence.

The small molecule inhibitor of SARS-CoV-2 3CLpro EDP-235 prevents viral replication and transmission in vivo.

The COVID-19 pandemic has led to the deaths of millions of people and severe global economic impacts. Small molecule therapeutics have played an important role in the fight against SARS-CoV-2, the virus responsible for COVID-19, but their efficacy has been limited in scope and availability, with many people unable to access their benefits, and better options are needed. EDP-235 is specifically designed to inhibit the SARS-CoV-2 3CLpro, with potent nanomolar activity against all SARS-CoV-2 variants to date, as well as clinically relevant human and zoonotic coronaviruses.

Anesthetic key points in a patient with a terminal ileum neuroendocrine tumor and a rare carcinoid left heart disease presented for non-cardiac surgery: case report.

Background: Carcinoid tumors are rare neuroendocrine malignancies presenting in an increasing number in our center. The incidence of carcinoid tumors is approximatively between 2.5 and 5 cases per 100,000 people of whom about 50% develop carcinoid syndrome.

Delayed Burr Hole Evacuation Compared With Acute Craniotomy for Acute Subdural Hematoma in Older Patients With Low-Energy Trauma.

Background Acute subdural hematomas commonly require emergent surgical decompression by craniotomy. There is currently limited research on alternative surgical strategies in the elderly population. This study investigates delayed surgical intervention for stable patients with low-energy trauma presenting with acute subdural hematomas.

Suprapubic versus transurethral catheterization for bladder drainage in male rectal cancer surgery (GRECCAR10), a randomized clinical trial.

Background: Bladder drainage is systematically used in rectal cancer surgery; however, the optimal type of drainage, transurethral catheterization (TUC) or suprapubic catheterization (SPC), is still controversial. The aim was to compare the rates of urinary tract infection on the fourth postoperative day (POD4) between TUC and SPC, after rectal cancer surgery regardless of the day of removal of the urinary drain.

Methods: This randomized clinical trial in 19 expert colorectal surgery centers in France and Belgium was performed between October 2016 and October 2019 and included 240 men (with normal or subnormal voiding function) undergoing mesorectal excision with low anastomosis for rectal cancer.

Plasma interferon-alpha protein levels during pregnancy are associated with lower birth weight in systemic lupus erythematosus.

Objectives: Adverse pregnancy outcomes are more common in women with systemic lupus erythematosus (SLE) compared with healthy women, but we lack prognostic biomarkers. Plasma interferon alpha (IFNα) protein levels are elevated in a subgroup of pregnant women with SLE, but whether this is associated with pregnancy outcomes is unknown. We investigated the relationship between IFNα, adverse pregnancy outcomes and the presence of autoantibodies in SLE pregnancy.

Tanzania's first Marburg Viral Disease outbreak response: Describing the roles of FELTP graduates and residents.

Viral Haemorrhagic Fever Outbreak presents a significant public health threat, requiring a timely, robust, and well-coordinated response. This paper aims to describe the roles of the Tanzania Field Epidemiology and Laboratory Training Program (TFELTP) graduates and residents in responding to Tanzania's first Marburg Viral Disease (MVD) outbreak. We performed a secondary data analysis using a range of documents, such as rosters of deployed responders and the TFELTP graduate and resident database, to count and describe them.

Structural and Dynamic Features of Acinetobacter baumannii OXA-66 β-Lactamase Explain Its Stability and Evolution of Novel Variants.

OXA-66 is a member of the OXA-51 subfamily of class D β-lactamases native to the Acinetobacter genus that includes Acinetobacter baumannii, one of the ESKAPE pathogens and a major cause of drug-resistant nosocomial infections. Although both wild type OXA-66 and OXA-51 have low catalytic activity, they are ubiquitous in the Acinetobacter genomes. OXA-51 is also remarkably thermostable.

Prenatal diagnosis of meningomyelocele resolves as a mature cystic teratoma in the thoracolumbar region.

A mature cystic teratoma is a mass with heterogeneous appearance, consisting of adult tissue with two or three layers: endoderm, mesoderm, and ectoderm. It is a rare, benign transformation of somatic tissue most commonly found in the sacrococcygeal region and may resemble an uncomplicated spina bifida on prenatal ultrasonography. In this case report, we describe a female newborn with an extremely rare mature cystic teratoma in the thoracolumbar region.

Coronary artery calcification and high-volume physical activity: role of lower intensity vs. longer duration of exercise.

Aims: While high-volume physical activity (PA) has been linked to elevated coronary artery calcification (CAC), the role of intensity vs. duration of PA has not been investigated. The purpose of the study was to examine the role of intensity vs.

Low CD4 + T cell count is related to specific anti-nuclear antibodies, IFNα protein positivity and disease activity in systemic lupus erythematosus pregnancy.

Background: Lymphopenia, autoantibodies and activation of the type I interferon (IFN) system are common features in systemic lupus erythematosus (SLE). We speculate whether lymphocyte subset counts are affected by pregnancy and if they relate to autoantibody profiles and/or IFNα protein in SLE pregnancy.

Methods: Repeated blood samples were collected during pregnancy from 80 women with SLE and 51 healthy controls (HC).

Tumor acidosis-induced DNA damage response and tetraploidy enhance sensitivity to ATM and ATR inhibitors.

Tumor acidosis is associated with increased invasiveness and drug resistance. Here, we take an unbiased approach to identify vulnerabilities of acid-exposed cancer cells by combining pH-dependent flow cytometry cell sorting from 3D colorectal tumor spheroids and transcriptomic profiling. Besides metabolic rewiring, we identify an increase in tetraploid cell frequency and DNA damage response as consistent hallmarks of acid-exposed cancer cells, supported by the activation of ATM and ATR signaling pathways.

Patient global assessment and inflammatory markers in patients with idiopathic inflammatory myopathies - A longitudinal study.

Aim: To explore if patient global assessment (PGA) is associated with inflammation over time and if associations are explained by other measures of disease activity and function in patients with idiopathic inflammatory myopathies (IIM).

Methods: PGA and systemic inflammatory markers prospectively collected over five years were retrieved from the International MyoNet registry for 1200 patients with IIM. Associations between PGA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and creatine kinase (CK) were analyzed using mixed models.