How PGL finds a sweet spot in phospholipid membranes: A combined multiscale MD and NMR study.

Glycolipids from pathogenic Mycobacterium tuberculosis play important roles during the interaction of the pathogen with macrophages and can shape the host cell's immune response by modulating its membrane structure and function. Here, we study the phenolic glycolipids (PGLs) present in the envelope of some hypervirulent strains of Mycobacterium tuberculosis and their impact on model membranes. By a combination of molecular modeling and simulations, and solid-state NMR experiments, we show that PGLs, such as the structurally related lipid phthiocerol dimycocerosate, adopt a conical shape in lipid membranes, which destabilizes the lamellar membrane phase and promotes a transition to a nonlamellar inverted-hexagonal phase.

Geographic distribution and associated mortality of invasive aspergillosis and mucormycosis among Medicare enrollees in the United States (2008-2015).

Background: Invasive mold infections-invasive aspergillosis and mucormycosis-have mortality rates as high as 90% in certain patient populations. Some clinical factors, such as prolonged neutropenia, are well-studied and are closely associated with increased mortality. However, the incidence of invasive aspergillosis and mucormycosis across geographic locations and its impact on mortality remains understudied.

Association of antimicrobial consumption with incidence across the departments of an academic medical centre.

Background: infection is a common gastrointestinal disease in healthcare settings, ranging from uncomplicated diarrhoea to life-threatening pseudomembranous colitis. It is associated with increased morbidity, mortality and healthcare costs. The aim of the study was to correlate CDI incidence with total and specific antibiotic consumption across 17 clinical departments of an academic hospital.

miR-363-5p- and IL-34-mediated modulation of pacemaker channel, HCN4, on iPSC-CM: Translation into the human sinus node microenvironment.

Background: The human sinus node (SN) contains cardiac fibroblasts and resident macrophages, with microRNAs (miRNAs) and interleukins as regulators of SN function. However, the mechanisms by which they influence heart rate remain unclear.

Objective: This study aimed to investigate the SN microenvironment, encompassing miRNAs, interleukins, macrophages, and fibroblasts and modulating induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and hence beating rate.

Integrating Nonindividual Patient Features in Machine Learning Models of Hospital-Onset Bacteremia.

Importance: Hospital-onset bacteremia and fungemia (HOB) are common and potentially preventable complications of hospital care.

Objective: To assess whether nonindividual patient features, which summarize interactions with other patients and health care workers (HCWs), can contribute to predictive and causal machine learning models for HOB.

Design, Setting, And Participants: This prognostic study included adult patients admitted to Barnes-Jewish Hospital, an academic hospital in St Louis, Missouri, in 2021.

Outcomes After Arthroscopic Posterior Labral Repair With All-Suture Anchors in Football Players.

Background: Posterior glenoid labral injuries are more common in football players than in the general population. Arthroscopic repair with all-suture anchors has proven to be an effective technique to address other abnormalities, allowing for low-profile constructs that minimize damage to surrounding tissue. Few studies have examined the outcomes of posterior labral repair with all-suture anchors in football players.

Facilitation as an effective strategy to reduce excessive antibiotic prophylaxis in Children's hospitals: A stepped-wedge cluster randomized controlled trial.

Background: Excessive use of postoperative prophylactic antibiotics in children's hospitals is a significant public health concern, leading to increased risks of infections like , multidrug-resistant organisms, and unnecessary healthcare costs. Antibiotic stewardship programs (ASPs) are designed to optimize antibiotic use, but ideal strategies for implementing evidence-based guidelines remain unclear. We tested facilitation, a dynamic process where trained individuals support healthcare personnel in bridging evidence-practice gaps, as a promising strategy for the de-implementation of unnecessary postoperative antibiotics in healthcare.

Influence of Disease Type and Activity on Adalimumab Exposure in Children with Inflammatory Rheumatic Diseases.

Understanding adalimumab pharmacokinetics (PK) in pediatric inflammatory rheumatic diseases (PIRD) could facilitate individualized treatment strategies. This pharmacometric (PMX) analysis, utilizing prospectively collected data, aimed to develop a PMX model investigating associations between disease-specific factors and adalimumab exposure in PIRD. PK data originating from a prospective two-center study including 36 children with PIRD (weight IQR: 33-55 kg) receiving subcutaneous adalimumab (IQR: 30-40 mg biweekly; n = 28 at steady state, n = 8 after first dose, i.

Outcomes of Glenoid Labral Repair Using All-Suture Anchors.

Background: In recent years, innovation in arthroscopic glenoid labral repair techniques has included the development of all-suture anchors. There are multiple potential advantages of all-suture anchors, including decreased bone removal, anchor migration, synovitis/chondral injury, and bone reaction. Despite these potential advantages, few studies have examined clinical outcomes of glenoid labral repair with all-suture anchors.

High-resolution 3D visualization of human hearts with emphases on the cardiac conduction system components-a new platform for medical education, mix/virtual reality, computational simulation.

Introduction: High-resolution digitized cardiac anatomical data sets are in huge demand in clinical, basic research and computational settings. They can be leveraged to evaluate intricate anatomical and structural changes in disease pathology, such as myocardial infarction (MI), which is one of the most common causes of heart failure and death. Advancements in high-resolution imaging and anatomical techniques in this field and our laboratory have led to vast improvements in understanding cardiovascular anatomy, especially the cardiac conduction system (CCS) responsible for the electricity of the heart, in healthy/aged/obese post-mortem human hearts.

Clinical Outcomes of Ulnar Collateral Ligament Repair With Internal Brace Versus Ulnar Collateral Ligament Reconstruction in Competitive Athletes.

Background: The increasing prevalence of ulnar collateral ligament (UCL) injuries, particularly in young athletes, necessitates optimization of treatment options. The introduction of UCL repair with internal bracing offers an exciting alternative to traditional UCL reconstruction.

Purpose: To compare midterm outcomes between UCL repair with internal bracing and UCL reconstruction in competitive athletes.

Identifying sex similarities and differences in structure and function of the sinoatrial node in the mouse heart.

Background: The sinoatrial node (SN) generates the heart rate (HR). Its spontaneous activity is regulated by a complex interplay between the modulation by the autonomic nervous system (ANS) and intrinsic factors including ion channels in SN cells. However, the systemic and intrinsic regulatory mechanisms are still poorly understood.

Performance of Risk Models for Antimicrobial Resistance in Adult Patients With Sepsis.

Importance: The results of prediction models that stratify patients with sepsis and risk of resistant gram-negative bacilli (GNB) infections inform treatment guidelines. However, these models do not extrapolate well across hospitals.

Objective: To assess whether patient case mix and local prevalence rates of resistance contributed to the variable performance of a general risk stratification GNB sepsis model for community-onset and hospital-onset sepsis across hospitals.

HIV replication and tuberculosis risk among people living with HIV in Europe: A multicohort analysis, 1983-2015.

Introduction: HIV replication leads to a change in lymphocyte phenotypes that impairs immune protection against opportunistic infections. We examined current HIV replication as an independent risk factor for tuberculosis (TB).

Methods: We included people living with HIV from 25 European cohorts 1983-2015.

Profiling Reduced Expression of Contractile and Mitochondrial mRNAs in the Human Sinoatrial Node vs. Right Atrium and Predicting Their Suppressed Expression by Transcription Factors and/or microRNAs.

(1) Background: The sinus node (SN) is the main pacemaker of the heart. It is characterized by pacemaker cells that lack mitochondria and contractile elements. We investigated the possibility that transcription factors (TFs) and microRNAs (miRs) present in the SN can regulate gene expression that affects SN morphology and function.

Understanding time to peak effect of propofol as sole agent on bispectral index in children aged 2-12 years.

Background: The pharmacodynamics of propofol in children have previously been described with the proprietary bispectral index (BIS) as an effect-site marker, and it has been suggested that the rate of onset of propofol might be age dependent, that is, a shorter time to peak effect in younger children. However, these analyses were potentially confounded by co-administered drugs, in particular opioids and benzodiazepines. Thus, the goal of this prospective study was to characterize the influence of age and weight on the onset of hypnotic effects from propofol, reflected by the time to peak of propofol effect-site concentration in the absence of additional drugs.

Interactive teaching of medical 3D cardiac anatomy: atrial anatomy enhanced by ECG and 3D visualization.

The most commonly applied way of teaching students to convey the foundations of human anatomy and physiology involves textbooks and lectures. This way of transmitting knowledge causes difficulties for students, especially in the context of three-dimensional imaging of organ structures, and as a consequence translates into difficulties with imagining them. Even despite the rapid uptake of knowledge dissemination provided by online materials, including courses and webinars, there is a clear need for learning programs featuring first-hand immersive experiences tailored to suit individual study paces.

Impact of hydroxyurea on follicle density in patients with sickle cell disease.

The impact of hydroxyurea (HU) on the ovarian reserve of female patients with sickle cell disease (SCD) remains poorly elucidated. Only direct histological analysis of ovarian follicle density can effectively evaluate HU's effect on ovarian reserve. By analyzing digitized slides of ovarian tissue from girls and young women with SCD who underwent ovarian tissue cryopreservation (OTC) before hematological stem cell transplantation, we meticulously counted follicles and categorized them based on their growth stage.

Morphology of human sinoatrial node and its surrounding right atrial muscle in the global obesity pandemic-does fat matter?

Introduction: The sinus node (SN) is the main pacemaker site of the heart, located in the upper right atrium at the junction of the superior vena cava and right atrium. The precise morphology of the SN in the human heart remains relatively unclear especially the SN microscopical anatomy in the hearts of aged and obese individuals. In this study, the histology of the SN with surrounding right atrial (RA) muscle was analyzed from young non-obese, aged non-obese, aged obese and young obese individuals.

Povidone Iodine vs Chlorhexidine Gluconate in Alcohol for Preoperative Skin Antisepsis: A Randomized Clinical Trial.

Importance: Preoperative skin antisepsis is an established procedure to prevent surgical site infections (SSIs). The choice of antiseptic agent, povidone iodine or chlorhexidine gluconate, remains debated.

Objective: To determine whether povidone iodine in alcohol is noninferior to chlorhexidine gluconate in alcohol to prevent SSIs after cardiac or abdominal surgery.

Novel Patient-Friendly Orodispersible Formulation of Ivermectin is Associated With Enhanced Palatability, Controlled Absorption, and Less Variability: High Potential for Pediatric Use.

Ivermectin has been used since the 1980s as an anthelmintic and antiectoparasite agent worldwide. Currently, the only available oral formulation is tablets designed for adult patients. A patient-friendly orodispersible tablet formulation designed for pediatric use (CHILD-IVITAB) has been developed and is entering early phase clinical trials.

Social Factors Associated With Congenital Syphilis in Missouri.

Background: Congenital syphilis disproportionately affects individuals impacted by adverse social determinants of health. Understanding these determinants may help facilitate holistic care.

Methods: We performed a retrospective review of mother-infant dyads with potential congenital syphilis in a Missouri hospital system.

Swissped-RECOVERY: masked independent adjudication for the interpretation of non-randomised treatment in a two-arm open-label randomised controlled trial (methylprednisolone vs immunoglobulins) in Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) involving 10 secondary and tertiary paediatric hospitals in Switzerland.

Objectives: In trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of trial findings. Swissped-RECOVERY was set up as one of the first randomised controlled trials worldwide, investigating the comparative effectiveness of anti-inflammatory treatment with intravenous methylprednisolone or intravenous immunoglobulins in children and adolescents with Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS).

Pharmacokinetics-Based Pediatric Dose Evaluation and Optimization Using Saliva - A Case Study.

Understanding pharmacokinetics (PK) in children is a prerequisite to determine optimal pediatric dosing. As plasma sampling in children is challenging, alternative PK sampling strategies are needed. In this case study we evaluated the suitability of saliva as alternative PK matrix to simplify studies in infants, investigating metamizole, an analgesic used off-label in infants.