Effect of host telomerase inhibition on human cytomegalovirus.

Unlabelled: Treatment options remain limited for human cytomegalovirus (HCMV). Host telomerase has been implicated in the pathogenesis and oncogenesis of multiple herpesviruses, most recently including HCMV. In this study, we investigated the effect of telomerase inhibition on HCMV replication, as well as the mechanism of the interaction between HCMV and host telomerase .

Connecting Past to Present: Does Historical Redlining Affect Current Life Expectancy?

Introduction: Previous research has documented a strong relationship between currently living in the redlined zones of the 1930s and suffering from a higher prevalence of disease. However, little is known about the relationship between historical redlining, modern-day redlining, and current resident health outcomes. This paper aimed to simultaneously model the associations between both historical redlining and modern-day redlining on current health outcomes.

A Case of Lemierre-Like Syndrome in a Pediatric Patient.

Lemierre-like syndrome is a rare, systemic sequelae following a persistent oropharyngeal infection, leading to septic thrombophlebitis of the internal jugular vein (IJV). Lemierre syndrome is caused by the obligate anaerobic organism , innate to the oropharyngeal tract. Lemierre-like syndrome is due to infections caused by other organisms, including methicillin-resistant (MRSA).

Improving Resident Hospital Discharge Communication by Changing Electronic Health Record Templates to Enhance Primary Care Provider Satisfaction.

Background And Objectives: Despite use of standardized electronic health record templates, the structure of discharge summaries may hinder communication from inpatient settings to primary care providers (PCPs). We developed an enhanced electronic discharge summary template to improve PCP satisfaction with written discharge summaries targeting diagnoses, medication reconciliation, laboratory test results, specialist follow-up, and recommendations.

Methods: Resident template usage was measured using statistical process control charts.

Diverse genetic spectrum among patients who met the criteria of hereditary breast, ovarian and pancreatic cancer syndrome.

Objective: Genetic high-risk assessment combines hereditary breast, ovarian and pancreatic cancer into one syndrome. However, there is a lack of data for comparing the germline mutational spectrum of the cancer predisposing genes between these three cancers.

Methods: Patients who met the criteria of the hereditary breast, ovarian and pancreatic cancer were enrolled and received multi-gene sequencing.

Real-world outcomes associated with vonoprazan-based proton pump inhibitor-based therapy for infection in Japan.

Background: Japanese guidelines recommend triple therapy with vonoprazan or a proton pump inhibitor (PPI) in combination with antibiotics to treat () infection. While studies have shown improved eradication rates and reduced costs with vonoprazan PPIs, there is little data describing healthcare resource use (HCRU) and treatment patterns.

Objectives: To compare patients treated with a vonoprazan-based or PPI-based regimen for infection in Japan in terms of their characteristics, HCRU, healthcare costs, clinical outcomes, and treatment patterns.

Aquagenic wrinkling of the palms: review of the literature.

Aquagenic wrinkling of the palms (AWP) is a rare dermatological disease characterized by development of rapid and excessive wrinkling and oedema of the palms and transient whitish or yellowish papules without erythema on the palmar surfaces after immersion in water. This phenomenon can be accompanied by pain and/or pruritus. The most common treatment of AWP involves aluminium-based topicals.

Direct health care costs associated with COVID-19 in the United States.

Data on the real-world health care burden of COVID-19 in the United States are limited. To compare health care resource use (HRU), direct health care costs, and long-term COVID-19-related complications between patients with vs patients without COVID-19 diagnoses. Using IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits administrative claims databases (January 1, 2018, to March 1, 2021), this retrospective, matched cohort study compared patients with a recorded COVID-19 diagnosis to control subjects with no recorded diagnosis for COVID-19, personal history of COVID-19, or pneumonia due to COVID-19.

High-fat diet disrupts REG3γ and gut microbial rhythms promoting metabolic dysfunction.

Gut microbial diurnal oscillations are important diet-dependent drivers of host circadian rhythms and metabolism ensuring optimal energy balance. However, the interplay between diet, microbes, and host factors sustaining intestinal oscillations is complex and poorly understood. Here, using a mouse model, we report the host C-type lectin antimicrobial peptide Reg3γ works with key ileal microbes to orchestrate these interactions in a bidirectional manner and does not correlate with the intestinal core circadian clock.

Impact of BRCA mutation on the survival and risk of contralateral breast cancer in Asian breast cancer patients.

Purpose: Breast cancer is increasing around the globe, including Asia. We aimed to examine the survival and risk of contralateral breast cancer (CBC) in Asian breast cancer patients with BRCA mutations.

Methods: A total of 128 breast cancer patients with germline BRCA mutations and 4,754 control breast cancer patients were enrolled.

Indirect comparison of apomorphine sublingual film and levodopa inhalation powder for Parkinson's disease 'OFF' episodes.

To compare efficacy of apomorphine sublingual film (APL) and levodopa inhalation powder (CVT-301) for 'on-demand' treatment of Parkinson's disease 'OFF' episodes. Patient-level data from an APL pivotal study were re-weighted to match average baseline characteristics from a CVT-301 study (SPAN-PD). Placebo-adjusted treatments were compared at week 12.

Medical costs for managing chronic kidney disease and related complications in patients with chronic kidney disease and type 2 diabetes.

Objective: To provide cost estimates for chronic kidney disease (CKD) management and major CKD complications among patients with CKD and type 2 diabetes (T2D).

Study Design: A retrospective cohort study of 52,599 adults with CKD and T2D using Optum Clinformatics claims data from 2014 to 2019.

Methods: Medical costs associated with CKD management, renal replacement therapies (RRTs), major CKD complications (eg, myocardial infarction, stroke, heart failure, atrial fibrillation, and hyperkalemia), and death were estimated using generalized estimating equations adjusting for baseline demographics, complications, and medical costs.

Circulating Tumor DNA as a Predictive Marker of Recurrence for Patients With Stage II-III Breast Cancer Treated With Neoadjuvant Therapy.

Background: Patients with stage II to III breast cancer have a high recurrence rate. The early detection of recurrent breast cancer remains a major unmet need. Circulating tumor DNA (ctDNA) has been proven to be a marker of disease progression in metastatic breast cancer.

Crossroads between membrane trafficking machinery and copper homeostasis in the nerve system.

Imbalanced copper homeostasis and perturbation of membrane trafficking are two common symptoms that have been associated with the pathogenesis of neurodegenerative and neurodevelopmental diseases. Accumulating evidence from biophysical, cellular and studies suggest that membrane trafficking orchestrates both copper homeostasis and neural functions-however, a systematic review of how copper homeostasis and membrane trafficking interplays in neurons remains lacking. Here, we summarize current knowledge of the general trafficking itineraries for copper transporters and highlight several critical membrane trafficking regulators in maintaining copper homeostasis.

Early-Life Microbial Restitution Reduces Colitis Risk Promoted by Antibiotic-Induced Gut Dysbiosis in Interleukin 10 Mice.

Background & Aims: Perturbations in the early-life gut microbiome are associated with increased risk for complex immune disorders like inflammatory bowel diseases. We previously showed that maternal antibiotic-induced gut dysbiosis vertically transmitted to offspring increases experimental colitis risk in interleukin (IL) 10 gene deficient (IL10) mice, a finding that may result from the loss/lack of essential microbes needed for appropriate immunologic education early in life. Here, we aimed to identify key microbes required for proper development of the early-life gut microbiome that decrease colitis risk in genetically susceptible animals.

Real-World Treatment Profiles, Clinical Outcomes, and Healthcare Resource Utilization of Patients with Migraine Prescribed Erenumab: A Multicenter Chart-Review Study of US Headache Centers.

Introduction: Erenumab, a first-in-class monoclonal antibody targeting the calcitonin gene-related peptide pathway, was approved by the US Food and Drug Administration in 2018 for the prevention of migraine in adults. There is limited data available on its impact in real-world settings. The study aim was to characterize the real-world treatment profiles, clinical outcomes, and healthcare resource utilization of patients prescribed erenumab from select major US headache centers.

The Effect of Numbered Jerseys on Directed Commands, Teamwork, and Clinical Performance During Simulated Emergencies.

Communication and teamwork are essential during inpatient emergencies such as cardiac arrest and rapid response (RR) codes. We investigated whether wearing numbered jerseys affect directed commands, teamwork, and performance during simulated codes. Eight teams of 6 residents participated in 64 simulations.

Quantifying the Oligomeric States of Membrane Proteins in Cells through Super-Resolution Localizations.

Transitions between different oligomeric states of membrane proteins are essential for proper cellular functions. However, the quantification of their oligomeric states in cells is technically challenging. Here we developed a new method to quantify oligomeric state(s) of highly expressed membrane proteins using the probability density function of molecule density ( PDF) calculated from super-resolution localizations.

Allele Specific Expression of MICA Variants in Human Fibroblasts Suggests a Pathogenic Mechanism.

The major histocompatibility complex class I chain-related gene A (MICA) is involved in immune responses of both nature killer (NK) cells and subsets of T cells with its receptor NKG2D. MICA is highly polymorphic in sequence which leads to MICA protein variants with distinct features. Specific polymorphisms of MICA have been associated with inflammatory diseases, including ankylosing spondylitis (AS), ulcerative colitis (UC) and Behçet's disease.

SIRT3 Is Crucial for Maintaining Skeletal Muscle Insulin Action and Protects Against Severe Insulin Resistance in High-Fat-Fed Mice.

Protein hyperacetylation is associated with glucose intolerance and insulin resistance, suggesting that the enzymes regulating the acetylome play a role in this pathological process. Sirtuin 3 (SIRT3), the primary mitochondrial deacetylase, has been linked to energy homeostasis. Thus, it is hypothesized that the dysregulation of the mitochondrial acetylation state, via genetic deletion of SIRT3, will amplify the deleterious effects of a high-fat diet (HFD).

Angiopoietin-like 4 (Angptl4) protein is a physiological mediator of intracellular lipolysis in murine adipocytes.

Intracellular triacylglycerol (TG) hydrolysis and fatty acid release by the white adipose tissue (WAT) during a fast is stimulated by counter-regulatory factors acting in concert, although how adipocytes integrate these lipolytic inputs is unknown. We tested the role of angiopoietin-like 4 (Angptl4), a secreted protein induced by fasting or glucocorticoid treatment, in modulating intracellular adipocyte lipolysis. Glucocorticoid receptor blockade prevented fasting-induced tissue Angptl4 expression and WAT TG hydrolysis in mice, and TG hydrolysis induced by fasts of 6 or 24 h was greatly reduced in mice lacking Angptl4 (Angptl4(-/-)).

Using physical models to study the gliding performance of extinct animals.

Aerodynamic studies using physical models of fossil organisms can provide quantitative information about how performance of defined activities, such as gliding, depends on specific morphological features. Such analyses allow us to rule out hypotheses about the function of extinct organisms that are not physically plausible and to determine if and how specific morphological features and postures affect performance. The purpose of this article is to provide a practical guide for the design of dynamically scaled physical models to study the gliding of extinct animals using examples from our research on the theropod dinosaur, †Microraptor gui, which had flight feathers on its hind limbs as well as on its forelimbs.

Releasable PEGylation of mesothelin targeted immunotoxin SS1P achieves single dosage complete regression of a human carcinoma in mice.

Recombinant immunotoxins exhibit targeting and cytotoxic functions needed for cell-specific destruction. However, antitumor efficacy, safety, and pharmacokinetics of these therapeutics might be improved by further macromolecular engineering. SS1P is a recombinant anti-mesothelin immunotoxin in clinical trials in patients with mesothelin-expressing tumors.