Structural effects of high laser power densities on an early bacteriorhodopsin photocycle intermediate.

Time-resolved serial crystallography at X-ray Free Electron Lasers offers the opportunity to observe ultrafast photochemical reactions at the atomic level. The technique has yielded exciting molecular insights into various biological processes including light sensing and photochemical energy conversion. However, to achieve sufficient levels of activation within an optically dense crystal, high laser power densities are often used, which has led to an ongoing debate to which extent photodamage may compromise interpretation of the results.

Biomechanical Comparison of Three Locking Compression Plate Constructs from Three Manufacturers under Cyclic Torsional Loading in a Fracture Gap Model.

Objective:  The aim of the study was to compare the stiffness and cyclic fatigue of locking compression plate constructs from three manufacturers, DePuy Synthes (DPS), Knight Benedikt (KB), and Provet Veterinary Instrumentation (Vi), under cyclic torsion.

Methods:  The constructs of DPS, KB, and Vi were assembled by fixing a 10-hole 3.5-mm stainless steel locking compression plate 1 mm away from a validated bone model with a fracture gap of 47 mm.

Capturing the blue-light activated state of the Phot-LOV1 domain from Chlamydomonas reinhardtii using time-resolved serial synchrotron crystallography.

Light-oxygen-voltage (LOV) domains are small photosensory flavoprotein modules that allow the conversion of external stimuli (sunlight) into intracellular signals responsible for various cell behaviors (e.g. phototropism and chloroplast relocation).

Nutrient-sensitizing drug repurposing screen identifies lomerizine as a mitochondrial metabolism inhibitor of chronic myeloid leukemia.

In chronic myeloid leukemia (CML), the persistence of leukemic stem cells (LSCs) after treatment with tyrosine kinase inhibitors (TKIs), such as imatinib, can lead to disease relapse. It is known that therapy-resistant LSCs rely on oxidative phosphorylation (OXPHOS) for their survival and that targeting mitochondrial respiration sensitizes CML LSCs to imatinib treatment. However, current OXPHOS inhibitors have demonstrated limited efficacy or have shown adverse effects in clinical trials, highlighting that identification of clinically safe oxidative pathway inhibitors is warranted.

Childhood vaccination trends during 2019 to 2022 in Tanzania and the impact of the COVID-19 pandemic.

The COVID-19 pandemic has significantly disrupted healthcare systems at all levels globally, notably affecting routine healthcare services, such as childhood vaccination. This study examined the impact of these disruptions on routine childhood vaccination programmes in Tanzania. We conducted a longitudinal study over four years in five Tanzanian regions: Mwanza, Dar es Salaam, Mtwara, Arusha, and Dodoma.

Achalasia-associated megaoesophagus presenting with dyspnoea and cough.

We present an unusual case of achalasia presenting with dyspnoea and persistent cough. These symptoms persisted for months, leading to the patient undergoing a chest X-ray by her general practitioner which showed right basal consolidation and a density extending along the right mediastinum. CT scan was done which revealed megaoesophagus with a diameter of 7 cm causing tracheal compression, as well as right basal consolidation, consistent with aspiration.

African foods for deep learning-based food recognition systems dataset.

African foods have socio-cultural significance that extends through migration, tourism, and marriage. Africans travel and integrate within the continent through intermarriages. There are over a thousand cultural aspects that differ such as language, food, dressing, beliefs and customs.

A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers.

Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we describe a multi-reservoir, high viscosity extruder as a step towards automation of sample delivery at XFELs.

An intellectual-disability-associated mutation of the transcriptional regulator impairs glutamatergic neurotransmission.

Advances in genome sequencing technologies have favored the identification of rare mutations linked to neurological disorders in humans. Recently, a autosomal dominant mutation in was identified (NM_052876.3: c.

Prothrombin Complex Concentrate vs Factor VII for Refractory Bleeding in Cardiac Surgery.

Background: Perioperative bleeding remains an important complication of cardiac surgery. Current guidelines support goal-directed use of coagulation factor concentrates in refractory bleeding, but the optimal strategy is unclear. Four-factor prothrombin complex concentrate (4F-PCC) has theoretical advantages over recombinant activated factor VII (rFVIIa) because of expanded mechanistic targets and lower rates of adverse events, but comparative data are limited.

Managing and Preventing Migraine in the Emergency Department: A Review.

Migraine is a leading cause of disability worldwide, and acute migraine attacks are a common reason for patients to seek care in the emergency department (ED). There have been recent advancements in the care of patients with migraine, specifically emerging evidence for nerve blocks and new pharmacological classes of medications like gepants and ditans. This article serves as a comprehensive review of migraine in the ED, including diagnosis and management of acute complications of migraine (eg, status migrainosus, migrainous infarct, persistent aura without infarction, and aura-triggered seizure) and use of evidence-based migraine-specific treatments in the ED.

Ultrafast structural changes direct the first molecular events of vision.

Vision is initiated by the rhodopsin family of light-sensitive G protein-coupled receptors (GPCRs). A photon is absorbed by the 11-cis retinal chromophore of rhodopsin, which isomerizes within 200 femtoseconds to the all-trans conformation, thereby initiating the cellular signal transduction processes that ultimately lead to vision. However, the intramolecular mechanism by which the photoactivated retinal induces the activation events inside rhodopsin remains experimentally unclear.

Watching the release of a photopharmacological drug from tubulin using time-resolved serial crystallography.

The binding and release of ligands from their protein targets is central to fundamental biological processes as well as to drug discovery. Photopharmacology introduces chemical triggers that allow the changing of ligand affinities and thus biological activity by light. Insight into the molecular mechanisms of photopharmacology is largely missing because the relevant transitions during the light-triggered reaction cannot be resolved by conventional structural biology.

Effects of Angled Dynamic Compression Holes in a Tibial Plateau Levelling Osteotomy Plate on Cranially Directed Fragment Displacement.

Objective:  To compare angled dynamic compression holes in a tibial plateau levelling osteotomy (TPLO) plate to a commercially available TPLO plate in an ovine cadaveric model.

Study Design:  Ovine tibias (40 bones) were mounted on a custom-made securement device and radiopaque markers were placed to aid radiographic measurements. A standard TPLO procedure was performed on each tibia with either a custom-made six-hole 3.

A spatio-temporal framework for modelling wastewater concentration during the COVID-19 pandemic.

The potential utility of wastewater-based epidemiology as an early warning tool has been explored widely across the globe during the current COVID-19 pandemic. Methods to detect the presence of SARS-CoV-2 RNA in wastewater were developed early in the pandemic, and extensive work has been conducted to evaluate the relationship between viral concentration and COVID-19 case numbers at the catchment areas of sewage treatment works (STWs) over time. However, no attempt has been made to develop a model that predicts wastewater concentration at fine spatio-temporal resolutions covering an entire country, a necessary step towards using wastewater monitoring for the early detection of local outbreaks.

Quantum kinematics in terms of observable quantities and the chirality of entangled two-qubit states.

We consider the kinematics of bipartite quantum states as determined by observable quantities, in particular the Bloch vectors of the subsystems. In examining the simplest case of a pair of two-level systems, there is a remarkable connection between the presence of non-classical correlations and the chirality of the two bases generated by the singular value decomposition of the correlation matrix of the Bloch vectors. We investigate the limits imposed by quantum mechanics of this effect and its relationship with other methods on quantifying the system's non-classical behavior.