Detection and characterisation of ligand-induced conformational changes in acetylcholine binding proteins using biosensors and X-ray crystallography.

Analysis of ligand-induced structural changes in proteins is challenging due to the lack of experimental methods suited for detection and characterisation of both ligand binding and induced structural changes. We have explored biosensors with different detection principles to study interactions between ligands and acetylcholine binding proteins (AChBPs), soluble homologues of Cys-loop ligand gated ion channels (LGICs) that undergo similar structural changes as LGICs upon ligand binding. X-ray crystallography was used to identify binding sites and establish if the detected conformational changes involved small changes in loop C or major structural changes in the pentamer associated with ion channel opening.

Gone With the Wind: Exploring a Vanished Rock Dove, , Hybrid Zone in the Sahara Desert.

Rock doves () are the wild ancestor of domestic and feral pigeons and had a wide distribution across Eurasia and the northern part of Africa. West African rock doves have been identified as genetically distinct from all other populations, possibly representing a distinct species. This divergence is hypothesized to have arisen through cycles of allopatry during the dry and wet Sahara periods.

Hydrogel-Mediated Sustained Delivery of Corneal Epithelial Extracellular Vesicles: A Strategy for Enhanced Corneal Regeneration.

Extracellular vesicles (EVs) derived from corneal epithelial cells have shown great promise in promoting corneal wound healing and stromal regeneration, but they face challenges with rapid clearance from the eye. This study addresses these challenges by developing a biocompatible collagen-hydrogel sustained delivery system. We successfully isolated, purified, and characterized corneal epithelial EVs (CE-EVs), assessed their efficacy in corneal epithelial healing in vitro, and demonstrated their sustained delivery over 10 days followed by an on-demand release through enzymatic degradation of the hydrogel, which mimics the in vivo scenario.

Defining metabolic abnormalities in acute human traumatic brain injury with cerebral microdialysis and multimodality monitoring.

Objective: We aimed to compare the prevalence and multimodal associations of mitochondrial dysfunction as defined by published cerebral-microdialysis-based criteria versus our novel multimodality-monitoring-based criteria in acute traumatic brain injury patients.

Methods: We retrospectively analyzed neurocritical care monitoring data from 619 acute traumatic brain injury patients. Monitoring modalities included cerebral microdialysis, intracranial pressure, brain tissue oxygenation, cerebral perfusion pressure, and the pressure reactivity index.

Social connectedness without eye contact: 18- but not 9-month-olds use proximal touch to infer third-party joint attention during observational learning.

Decades of research have highlighted the important role of joint attention in early cultural learning. However, most previous studies focused on a limited range of joint attention settings involving the learner's participation in joint attention, characterized by eye contact and triadic gaze following. This has created an incomplete picture, tending to neglect the diversity in which infants experience social connectedness in their daily lives.

COMT inhibition with entacapone for patients with Parkinson's disease and motor complications: the novelty of continuous infusion.

Enhancing levodopa efficacy through peripheral COMT inhibition and using continuous infusion are both established strategies for managing motor fluctuations. Both approaches aim to improve the pharmacokinetics of levodopa in order to maintain a steady delivery of levodopa to the brain, avoid the deep troughs in levodopa plasma concentrations associated with oral levodopa delivery, and thereby reduce OFF time. In this review, we describe the pharmacologic rationale for combining COMT inhibition with entacapone and continuous dopaminergic delivery that led to the development of levodopa/entacapone/carbidopa intestinal gel (LECIG).

Frontiers Shaping the Next Generation of Transformation Product Prediction and Toxicological Assessment.

The characterization of transformation products (TPs) is crucial for understanding chemical fate and potential environmental hazards. TPs form through (a)biotic processes and can be detected in environmental concentrations comparable to or even exceeding their parent compounds, indicating toxicological relevance. However, identifying them is challenging due to the complexity of transformation processes and insufficient data.

Combining mental health and climate-smart agricultural interventions to improve food security in humanitarian settings: study protocol for the THRIVE cluster-randomized controlled trial with mothers in Nakivale refugee settlement, Uganda.

Background: Climate extremes in Africa threaten the food security of war-affected refugees, who often experience mental health challenges that hinder their capacity for agricultural adaptation. Cost-effective, climate-smart farming interventions are crucial for addressing food insecurity in humanitarian contexts, yet evidence on their effectiveness is limited, and the potential benefits of integrating them with mental health interventions remain unexplored. We hypothesize that the success of agricultural interventions, especially under adversity, is influenced by mental health and psychological functioning.

Molecular epidemiology of extended-spectrum beta-lactamase producing Gram-negative bacteria among surgical site infection patients in Ethiopia: a multicenter prospective study.

Extended-spectrum beta-lactamases (ESBLs) producing Gram-negative bacteria are public health threats. This study aims to characterize ESBL-producing Gram-negative bacteria (GNB) isolated from surgical site infection patients. A multicenter cross-sectional study was conducted at four hospitals located in central (Addis Ababa), southern (Hawassa), northern (Debre Tabor), and Southwestern (Jimma) parts of Ethiopia.

Immune-coagulation dynamics in severe COVID-19 revealed by autoantibody profiling and multi-omics integration.

Severe COVID-19 is characterized by immune-coagulation dysregulation, yet the contribution of related autoantibodies remains poorly understood. We investigated relationships between plasma autoantibody reactivities, whole-blood transcriptomics, plasma proteomics, and clinical laboratory parameters in a cohort of hospitalized COVID-19 patients. Transcriptomic analysis revealed that 42 curated coagulation and complement cascade genes were upregulated in severe cases compared to healthy controls, with 15 genes, including CR1L, ELANE, ITGA2B, ITGB3, VWF, TFPI, PROS1, MMRN1, and SELP (> 1.

Trends in inhaler use and associated carbon footprint: a sales data-based study in Europe.

Background: Physicians are being encouraged to favour dry powder inhalers (DPI) over pressurised metered dose inhalers (pMDI) on environmental grounds. The EU is reviewing the F-gas regulation to accelerate emission phase-down targets. Thoughtful use of inhalers can reduce emissions while promoting positive clinical outcomes.

Anticoagulation and antiplatelet strategies used in Sweden in patients with myocardial infarction and concomitant atrial fibrillation: nationwide cohort study.

Background: Optimal antithrombotic therapy and its duration, whether triple therapy with dual antiplatelets plus oral anticoagulant (OAC), or dual antithrombotic therapy with an antiplatelet plus OAC, is uncertain for patients with myocardial infarction (MI) and atrial fibrillation (AF).

Methods: Patients registered in SWEDEHEART (Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies) for their first MI between 2011 and 2021 with a history or new-onset AF were included (n=26 574). Linkage between SWEDEHEART and Swedish administrative health databases was performed, and pseudonymised data analysed.

Evidence for deliberate burial of the dead by .

In this study, we describe new results of excavations in the Dinaledi Subsystem of the Rising Star cave system, South Africa. In two areas within the Hill Antechamber and the Dinaledi Chamber, this work uncovered concentrations of abundant fossils including articulated, matrix-supported skeletal regions consistent with rapid covering by sediment prior to the decomposition of soft tissue. We additionally re-examine the spatial positioning of skeletal material and associated sediments within the Puzzle Box area, from which abundant remains representing a minimum of six individuals were recovered in 2013 and 2014.

Language, Speech, and Oral Motor Performance in Children With Developmental Coordination Disorder: A Systematic Review.

Background: Developmental coordination disorder is a neurodevelopmental disorder characterised by motor difficulties that significantly and persistently impact activities of daily living and participation. It has been suggested that children with (probable) developmental coordination disorder (pDCD) experience challenges in the domain of language, speech, and oral motor development.

Aim: This systematic review provides an overview of recent studies assessing challenges in these domains in children with (p)DCD.

Host Traits Impact the Outcome of Metagenomic Library Preparation From Dental Calculus Samples Across Diverse Mammals.

Dental calculus metagenomics has emerged as a valuable tool for studying the oral microbiomes of humans and a few select mammals. With increasing interest in wild animal microbiomes, it is important to understand how widely this material can be used across the mammalian tree of life, refine the related protocols and understand the expected outcomes and potential challenges of dental calculus sample processing. In this study, we significantly expand the breadth of studied host species, analysing laboratory and bioinformatics metadata of dental calculus samples from 32 ecologically and phylogenetically diverse mammals.

Global metabolomics profiling of glucuronides in human plasma, fecal, and cerebrospinal fluid samples.

Glucuronidation is the major phase II biotransformation reaction that facilitates the clearance of exogenous compounds from the human body. Glucuronidated metabolites have been investigated in urine samples at a broad scale; however, their characterization in other human biospecimens is underexplored. Our study has now performed a comprehensive profiling of glucuronides in plasma, fecal, and cerebrospinal fluid (CSF) of humans.

Ticagrelor and Aspirin or Aspirin Alone after Coronary Surgery for Acute Coronary Syndrome.

Background: Patients benefit from antiplatelet therapy after coronary-artery bypass grafting (CABG) for an acute coronary syndrome. Whether the addition of ticagrelor to aspirin, as compared with aspirin alone, further reduces the risk of adverse cardiovascular outcomes is unclear.

Methods: In this open-label, registry-based, clinical trial conducted at 22 Nordic cardiothoracic surgery centers, we randomly assigned patients in a 1:1 ratio to receive either ticagrelor plus aspirin or aspirin alone for 1 year after CABG for an acute coronary syndrome.

Identification of cystatin C as a new marker of glomerular filtration rate, and of shrunken pore syndrome - a new kidney disorder defining selective glomerular hypofiltration syndromes - calls for expansion of the international KDIGO guidelines.

Cystatin C was identified as a marker of glomerular filtration rate (GFR) in 1979, and the parallel analysis of cystatin C and creatinine led to the identification of shrunken pore syndrome (SPS) - a new kidney disorder - in 2015. Since then, it has been shown that cystatin C in many aspects is superior to creatinine as a marker of GFR and cardiovascular risk. SPS, an entity within the selective glomerular hypofiltration syndromes (SGHS), has been demonstrated to be associated with a strong increase in morbidity and mortality in several populations.

Effects of anticoagulation in patients with device-detected atrial fibrillation and multiple stroke risk factors: a win ratio analysis of the NOAH-AFNET 6 trial.

Aims: Patients with device-detected atrial fibrillation (DDAF) have a lower stroke risk than those with ECG-diagnosed AF, requiring careful evaluation of oral anticoagulation benefits vs. its inherent bleeding risk.

Methods And Results: An unmatched win ratio analysis was performed of the NOAH-AFNET 6 trial dataset, using components of the primary efficacy and safety outcomes of the trial.

Fun Leads the Way-Healthcare Staff's Experiences of Promoting Physical Activity Among Children Who Survived a Brain Tumor: A Qualitative Study.

The majority of children who survive a brain tumor suffer from late effects. Physical activity can have a positive impact on physical fitness and mitigate late effects. Despite this, survivors are less physically active than their peers.

Proteomics-enabled learning machine algorithms enhance the prediction of cardiovascular diseases in patients with type 2 diabetes mellitus.

Background And Aims: Estimating the risk of cardiovascular disease (CVD) complications in type 2 diabetes mellitus (T2DM) patients is critical in the medical decision-making process. This study aimed to use a machine learning technique combined with proteomics to develop personalized models for predicting CVD in patients with T2DM.

Methods And Results: In total, 874 patients with T2DM and 2,920 Olink proteins obtained from the UK Biobank were used in this study.

Integrative proteomic analysis provides novel therapeutic insights for etiological subtypes of diabetes.

Aims: Type 2 diabetes (T2D) is a highly heterogeneous disease characterised by subtypes with variations in aetiology, disease progression, and risk of complications. However, potential drug targets for these subtypes have not been explored. This study aims to investigate potential drug targets by integrating proteomics.

Maternal and Interpregnancy Factors and Risks of First-Time Preeclampsia in Second Pregnancy: A Swedish National Cohort Study.

Objective: To investigate factors associated with first-time preeclampsia in second pregnancies.

Design: Population-based cohort study using Swedish national registers.

Setting: Sweden 1992-2019.

Helicobacter pylori Screening After Acute Myocardial Infarction: The Cluster Randomized Crossover HELP-MI SWEDEHEART Trial.

Importance: Upper gastrointestinal bleeding is common after myocardial infarction.

Objective: To determine whether routine screening for Helicobacter pylori infection during hospitalization for myocardial infarction reduces bleeding events and improves clinical outcomes.

Design, Setting, And Participants: A nationwide, open-label, 2-period, 2-sequence, cluster randomized, crossover clinical trial using a clinical registry for study population definition and data collection merged with national Swedish health data registries.