Breastfeeding, pregnancy, medicines, neurodevelopment, and population databases: the information desert.

Background: The pharmacoepidemiology of the long-term benefits and harms of medicines in pregnancy and breastfeeding has received little attention. The impact of maternal medicines on children is increasingly recognised as a source of avoidable harm. The focus of attention has expanded from congenital anomalies to include less visible, but equally important, outcomes, including cognition, neurodevelopmental disorders, educational performance, and childhood ill-health.

Transmission of SARS-CoV-2 among children and staff in German daycare centres.

In daycare centres, the close contact of children with other children and employees favours the transmission of infections. The majority of children <6 years attend daycare programmes in Germany, but the role of daycare centres in the SARS-CoV-2 pandemic is unclear. We investigated the transmission risk in daycare centres and the spread of SARS-CoV-2 to associated households.

The enigma of mixed connective tissue disease-challenges in routine care.

Objectives: As a rare and heterogeneous disease, mixed connective tissue disease (MCTD) represents a challenge. Herein, we aimed to unravel potential pitfalls including correct referral diagnosis, distinction from other connective tissue diseases (CTD) and treatment modalities.

Methods: We characterised the MCTD cohort at our tertiary referral centre.

Differential Surface Adsorption Phenomena for Conventional and Novel Surfactants Correlates with Changes in Interfacial mAb Stabilization.

Protein adsorption on surfaces can result in loss of drug product stability and efficacy during the production, storage, and administration of protein-based therapeutics. Surface-active agents (excipients) are typically added in protein formulations to prevent undesired interactions of proteins on surfaces and protein particle formation/aggregation in solution. The objective of this work is to understand the molecular-level competitive adsorption mechanism between the monoclonal antibody (mAb) and a commercially used excipient, polysorbate 80 (PS80), and a novel excipient, -myristoyl phenylalanine--polyetheramine diamide (FM1000).

Targeted Plasmalogen Supplementation: Effects on Blood Plasmalogens, Oxidative Stress Biomarkers, Cognition, and Mobility in Cognitively Impaired Persons.

Plasmalogens are a specific type of glycerophospholipid found in especially high levels in neuronal membranes. Decreased blood and brain levels of docosahexaenoic acid (DHA) containing plasmalogens are associated with decreased cognition and neuromuscular function in humans. Administration of 1-O-alkyl-2-acylglycerol (AAG) plasmalogen precursors containing DHA at the sn-2 position dose-dependently increase blood DHA plasmalogens and are neuroprotective in animal models of neurodegeneration at doses between 10 and 50 mg/kg.

Modification of the Association Between Frequent Aspirin Use and Ovarian Cancer Risk: A Meta-Analysis Using Individual-Level Data From Two Ovarian Cancer Consortia.

Purpose: Frequent aspirin use has been associated with reduced ovarian cancer risk, but no study has comprehensively assessed for effect modification. We leveraged harmonized, individual-level data from 17 studies to examine the association between frequent aspirin use and ovarian cancer risk, overall and across subgroups of women with other ovarian cancer risk factors.

Methods: Nine cohort studies from the Ovarian Cancer Cohort Consortium (n = 2,600 cases) and eight case-control studies from the Ovarian Cancer Association Consortium (n = 5,726 cases) were included.

Hospital length of stay among children with and without congenital anomalies across 11 European regions-A population-based data linkage study.

Background: Congenital anomalies are a leading cause of childhood morbidity, but little is known about the long-term outcomes.

Objective: To quantify the burden of disease in childhood for children with congenital anomalies by assessing the risk of hospitalisation, the number of days spent in hospital and proportion of children with extended stays (≥10 days).

Methods: European population-based record-linkage study in 11 regions in eight countries including children with congenital anomalies (EUROCAT children) and without congenital anomalies (reference children) living in the same regions.

Do Soluble Phosphates Direct the Formose Reaction towards Pentose Sugars?

The formose reaction has been a leading hypothesis for the prebiotic synthesis of sugars such as ribose for many decades but tends to produce complex mixtures of sugars and often tars. Channeling the formose reaction towards the synthesis of biologically useful sugars such as ribose has been a of origins-of-life research. Here, we tested the hypothesis that a simple, prebiotically plausible phosphorylating agent, acetyl phosphate, could direct the formose reaction towards ribose through phosphorylation of intermediates in a manner resembling gluconeogenesis and the pentose phosphate pathway.

Mentoring Medical Education Research: Guidelines from a Narrative Review.

Unlabelled: Mentorship is critical to develop research scholars. Current literature provides mentorship guidance for biomedical research; however, mentorship for educational research is scarce. We explored literature to offer evidence-based guidance for medical education research mentors.

Neurological Complications and Clinical Outcomes of Infective Endocarditis.

Objectives: The aim of this study is to explore the clinical features associated with neurological complications of infective endocarditis (IE) and to assess the impact of neurological complications on clinical outcomes.

Materials And Methods: The frequency of relevant clinical features was compared in a case series of IE patients with and without neurological complications admitted to a single health care system from 2015 to 2019. Variables with significant differences (p ≤ 0.

Evidence of surface contamination in hospital rooms occupied by patients infected with monkeypox, Germany, June 2022.

The extent of monkeypox virus environmental contamination of surfaces is unclear. We examined surfaces in rooms occupied by two monkeypox patients on their fourth hospitalisation day. Contamination with up to 105 viral copies/cm2 on inanimate surfaces was estimated by PCR and the virus was successfully isolated from surfaces with more than 106 copies.

Wheeze in the time of COVID-19: overcoming obstacles to an unusual diagnosis.

This case is an example of a rare cause of a common clinical presentation (persistent lobar collapse with wheeze). We describe patient management from primary care through to a national thoracic referral centre. We highlight the importance of objective testing to support an asthma diagnosis and the need to consider alternative or additional diagnoses if a patient does not respond to treatment or the clinical course is unexpected.

Molecular subclassification of vulvar squamous cell carcinoma: reproducibility and prognostic significance of a novel surgical technique.

Objectives: Vulvar squamous cell carcinoma is subclassified into three prognostically relevant groups: (i) human papillomavirus (HPV) associated, (ii) HPV independent p53 abnormal (mutant pattern), and (iii) HPV independent p53 wild type. Immunohistochemistry for p16 and p53 serve as surrogates for HPV viral integration and mutational status. We assessed the reproducibility of the subclassification based on p16 and p53 immunohistochemistry and evaluated the prognostic significance of vulvar squamous cell carcinoma molecular subgroups in a patient cohort treated by vulvar field resection surgery.

Generation of functional human oligodendrocytes from dermal fibroblasts by direct lineage conversion.

Oligodendrocytes, the myelinating cells of the central nervous system, possess great potential for disease modeling and cell transplantation-based therapies for leukodystrophies. However, caveats to oligodendrocyte differentiation protocols ( Ehrlich et al., 2017; Wang et al.

Noninvasive Delivery of Biologicals to the Brain.

In the past, psychotherapy and neuropharmacological approaches have been the most common treatments for disordered thoughts, moods, and behaviors. One new path of brain therapeutics is in the deployment of noninvasive approaches designed to reprogram brain function at the cellular level. Treatment at the cellular level may be considered for a wide array of disorders, ranging from mood disorders to neurodegenerative disorders.

Screening neuroimaging in neurologically asymptomatic patients with infective endocarditis.

Background And Purpose: Neurological complications from infective endocarditis (IE) are common and often present with minimal clinical symptoms. In this study, we examine whether screening neuroimaging in asymptomatic patients results in increased detection of neurological complications and leads to improved patient outcomes.

Methods: Using a database of consecutive adults with IE admitted to a single health system from 2015 to 2019, we selected patients who presented without any neurological symptoms and determined whether these patients underwent screening neuroimaging.

Small effects of livestock grazing intensification on diversity, abundance, and composition in a dryland plant community.

Livestock grazing is a globally important land use and has the potential to significantly influence plant community structure and ecosystem function, yet several critical knowledge gaps remain on the direction and magnitude of grazing impacts. Furthermore, much of our understanding of the long-term effects on plant community composition and structure are based on grazer exclusion experiments, which explicitly avoid characterizing effects along grazing intensity gradients. We sampled big sagebrush plant communities using 68 plots located along grazing intensity gradients to determine how grazing intensity influences multiple aspects of plant community structure over time.

Proposed energy-metabolisms cannot explain the atmospheric chemistry of Venus.

Life in the clouds of Venus, if present in sufficiently high abundance, must be affecting the atmospheric chemistry. It has been proposed that abundant Venusian life could obtain energy from its environment using three possible sulfur energy-metabolisms. These metabolisms raise the possibility of Venus's enigmatic cloud-layer SO-depletion being caused by life.

Temporal and geographical variations in survival of children born with congenital anomalies in Europe: A multi-registry cohort study.

Background: Congenital anomalies are a major cause of perinatal, neonatal and infant mortality.

Objectives: The aim was to investigate temporal changes and geographical variation in survival of children with major congenital anomalies (CA) in different European areas.

Methods: In this population-based linkage cohort study, 17 CA registries members of EUROCAT, the European network for the surveillance of CAs, successfully linked data on 115,219 live births with CAs to mortality records.

Long term tolerability and clinical outcomes associated with tocilizumab in the treatment of refractory antibody mediated rejection (AMR) in pediatric renal transplant recipients.

Background: Treatment options for antibody-mediated rejection (AMR) are limited. Recent studies have shown that inhibition of interleukin-6 (IL-6)/interleukin-6 receptor (IL-6R) signaling can reduce inflammation and slow AMR progression.

Methods: We report our experience using monthly tocilizumab (anti-IL6R) in 25 pediatric renal transplant recipients with AMR, refractory to IVIg/Rituximab.