A multifaceted intervention to improve diagnosis and early management of hospitalised patients with suspected acute brain infections in Brazil, India, and Malawi: an international multicentre intervention study.

Background: Brain infections pose substantial challenges in diagnosis and management and carry high mortality and morbidity, especially in low-income and middle-income countries. We aimed to improve the diagnosis and early management of patients admitted to hospital (adults aged 16 years and older and children aged >28 days) with suspected acute brain infections at 13 hospitals in Brazil, India, and Malawi.

Methods: With hospital stakeholders, policy makers, and patient and public representatives, we co-designed a multifaceted clinical and laboratory intervention, informed by an evaluation of routine practice.

A family of bacterial actin homologs forms a three-stranded tubular structure.

The cytoskeleton is crucial for cell organization and movement. In Eukaryotes, it largely consists of the protein actin, that forms a double-stranded linear filamentous structure in the presence of ATP and disassemble upon ATP hydrolysis. Bacteria also possess actin homologs, that drive fundamental cellular processes, including cell division, shape maintenance, and DNA segregation.

Tracking pollen tube and ovule development reveals rapid responses to pollination in .

Pollination and subsequent fertilization in most angiosperms are precursors of seed and fruit development. Thus, understanding the developmental processes can improve the management of plant reproductive success and food security. Indeed, the window between ovule fertilization and seed development is crucial for the accumulation of metabolites which determines ultimate seed quality and yield.

Patient Determinants and Effects on Adherence of Adverse Drug Reactions to Tuberculosis Treatment: A Prospective Cohort Analysis.

Background: Adverse drug reactions (ADRs) to tuberculosis (TB) medications make treatment completion challenging. We investigated the impact of alcohol, human immunodeficiency virus (HIV), and other patient determinants on ADRs and treatment adherence.

Methods: We administered monthly ADR questionnaires to participants with TB in Worcester, South Africa.

Severe accidental poisonings in children: a British Paediatric Surveillance Unit nationwide prospective study.

Background: Poisoning in children and young people is common. Understanding the incidence, causes and circumstances of severe accidental poisonings, requiring admission and medical intervention, may help healthcare professionals and shape public health interventions.

Methods: A prospective, population-based surveillance study using the British Paediatric Surveillance Unit (BPSU)'s active surveillance methodology (July 2018-July 2019) in the UK and Ireland.

Vitamin B2 Operates by Dual Thermodynamic and Kinetic Mechanisms to Selectively Tailor Urate Crystallization.

Here we demonstrate how a biologically relevant molecule, riboflavin (vitamin B2), operates by a dual mode of action to effectively control crystallization of ammonium urate (NHHU), which is associated with cetacean kidney stones. In situ microfluidics and atomic force microscopy experiments confirm a strong interaction between riboflavin and NHHU crystal surfaces that substantially inhibits layer nucleation and spreading by kinetic mechanisms of step pinning and kink blocking. Riboflavin does not alter the distribution of tautomeric urate isomers, but its adsorption on NHHU crystal surfaces does interfere with the effects of minor urate tautomer by limiting its ability to induce NHHU crystal defects while also suppressing NHHU nucleation and inhibiting crystal growth by 80% at an uncharacteristically low modifier concentration.

IL-1β-driven NF-κB transcription of ACE2 as a Mechanism of Macrophage Infection by SARS-CoV-2.

Coronavirus disease 2019 (COVID-19), caused by infection with the enveloped RNA betacoronavirus, SARS-CoV-2, led to a global pandemic involving over 7 million deaths. Macrophage inflammatory responses impact COVID-19 severity; however, it is unclear whether macrophages are infected by SARS-CoV-2. We sought to identify mechanisms regulating macrophage expression of ACE2, the primary receptor for SARS-CoV-2, and to determine if macrophages are susceptible to productive infection.

Metabolic response of Klebsiella oxytoca to ciprofloxacin exposure: a metabolomics approach.

Introduction: Rapid detection and identification of pathogens and antimicrobial susceptibility is essential for guiding appropriate antimicrobial therapy and reducing morbidity and mortality associated with sepsis.

Objectives: The metabolic response of clinical isolates of Klebsiella oxytoca exposed to different concentrations of ciprofloxacin (the second generation of quinolones antibiotics) were studied in order to investigate underlying mechanisms associated with antimicrobial resistance (AMR).

Methods: Metabolomics investigations were performed using Fourier-transform infrared (FT-IR) spectroscopy as a metabolic fingerprinting approach combined with gas chromatography-mass spectrometry (GC-MS) for metabolic profiling.

Improved Automated Radiosynthesis of [F]Dolutegravir: Toward Clinical Applications.

Positron emission tomography imaging using radiolabeled dolutegravir (DTG) is an interesting approach to understand the biodistribution of this antiretroviral drug at HIV-1 sanctuary sites. In the course of clinical translation, we depict herein an improved and pharmaceutically compliant radiosynthesis of [F]DTG from an original tin precursor. The radiosynthesis was achieved in two steps by copper-mediated radiofluorination, followed by enol ether deprotection using a kit-based AllInOne module.

Polyoxometalate inhibition of SOX2-mediated tamoxifen resistance in breast cancer.

Background: Increased cancer stem cell (CSC) content and SOX2 overexpression are common features in the development of resistance to therapy in hormone-dependent breast cancer, which remains an important clinical challenge. SOX2 has potential as biomarker of resistance to treatment and as therapeutic target, but targeting transcription factors is also challenging. Here, we examine the potential inhibitory effect of different polyoxometalate (POM) derivatives on SOX2 transcription factor in tamoxifen-resistant breast cancer cells.

Whole-body distribution of tenofovir, emtricitabine and dolutegravir in non-human primates.

Background: One major barrier to HIV cure is the persistence of virus, possibly linked to an insufficient antiretroviral drug (ARV) distribution into tissues.

Objectives: To draw the whole-body distribution of three antiretroviral drugs-tenofovir disoproxil fumarate, emtricitabine and dolutegravir-in non-human primates (NHPs).

Methods: Eight uninfected NHPs received a single injection of a solution containing the three ARVs.

Rapid Classification and Differentiation of Sepsis-Related Pathogens Using FT-IR Spectroscopy.

Sepsis is a life-threatening condition arising from a dysregulated host immune response to infection, leading to a substantial global health burden. The accurate identification of bacterial pathogens in sepsis is essential for guiding effective antimicrobial therapy and optimising patient outcomes. Traditional culture-based bacterial typing methods present inherent limitations, necessitating the exploration of alternative diagnostic approaches.

The impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs.

Background: In South Africa, an estimated 11% of the population have high alcohol use, a major risk factor for TB. Alcohol and other substance use are also associated with poor treatment response, with a potential mechanism being altered TB drug pharmacokinetics.

Objectives: To investigate the impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs in participants with pulmonary TB.

An incentive-based text-messaging intervention to reduce maternal alcohol use during pregnancy and lactation in South Africa (MaRISA study): Findings from a single-arm pilot study.

Background: South Africa has the highest rate of fetal alcohol spectrum disorders (FASD) globally. As with alcohol use during pregnancy, alcohol consumption while breastfeeding adversely impacts infant development. We pilot tested an incentive-based text-messaging intervention to reduce alcohol use during pregnancy and lactation in South Africa.

The Rapid Emergence of Hypervirulent Species and as Major Health Threats in Southeast Asia: The Urgent Need for Recognition as Neglected Tropical Diseases.

The World Health Organization (WHO)'s list of neglected tropical diseases (NTDs) highlights conditions that are responsible for devastating health, social and economic consequences, and yet, they are overlooked and poorly resourced. The NTD list does not include conditions caused by Gram-negative bacilli (GNB). Infections due to GNB cause significant morbidity and mortality and are prevalent worldwide.

The overlap of accessory virulence factors and multidrug resistance among clinical and surveillance Klebsiella pneumoniae isolates from a neonatal intensive care unit in Nepal: a single-centre experience in a resource-limited setting.

Background: There is a lack of data on the characteristics of overlap between acquired antimicrobial resistance and virulence factors in Klebsiella pneumoniae in high-risk settings, especially with the inclusion of surveillance isolates along with the clinical. We investigated K. pneumoniae isolates, from a neonatal intensive care unit (NICU) in Nepal, for the presence of both accessory virulence factors and acquired antimicrobial resistance.

Perceptions of perinatal alcohol use and treatment needs in Cape Town, South Africa: a qualitative study.

Background: South Africa has one of the world's highest rates of foetal alcohol spectrum disorders (FASD). Recent evidence also showed that alcohol use during lactation significantly compromises child development in children exposed to alcohol through breastfeeding, independent of prenatal alcohol exposure. This study explored perceptions of perinatal alcohol use and treatment needs in Cape Town, South Africa, to inform the development of an intervention to encourage alcohol abstinence during pregnancy and breastfeeding.

The causes of bacterial bloodstream infections and antimicrobial resistance patterns in children attending a secondary care hospital in Bhaktapur, Nepal, 2017-2022: a retrospective study.

Objectives: Data on antimicrobial resistance (AMR) among children in Nepal are limited. Here we have characterized the causes of bacterial bloodstream infections (BSIs), antimicrobial resistance patterns and the mechanisms of β-lactamase production in Enterobacterales among children attending outpatient and inpatient departments of a secondary care paediatric hospital in Nepal.

Methods: We retrospectively collected demographic and clinical data of culture-proven bacterial BSIs between January 2017 and December 2022 among children <18 years attending a 50-bedded paediatric hospital.

Identifying and Validating Alcohol Diagnostics for Injury-Related Trauma in South Africa: Protocol for a Mixed Methods Study.

Background: The burden of alcohol use among patients with trauma and the relative injury risks is not routinely measured in South Africa. Given the prominent burden of alcohol on hospital trauma departments, South Africa needs practical, cost-effective, and accurate alcohol diagnostic tools for testing, surveillance, and clinical management of patients with trauma.

Objective: This study aims to validate alcohol diagnostics for injury-related trauma and assess its use for improving national health practice and policy.