High versus low dose of 14 days treatment of primaquine in infected patients in Cambodia: a randomised open-label efficacy study.

Background: The WHO malaria treatment guidelines recommend a total dose in the range of 3·5 to 7·0 mg/kg of primaquine to eliminate () hypnozoites and prevent relapses. There are however indications that for tropical isolates, notably from Southeast Asia, the lower dose of 3·5 mg/kg is insufficient. Determining the most effective regimen to eliminate hypnozoites is needed to achieve elimination of this malaria parasite.

Structural basis for the conformational protection of nitrogenase from O.

The low reduction potentials required for the reduction of dinitrogen (N) render metal-based nitrogen-fixation catalysts vulnerable to irreversible damage by dioxygen (O). Such O sensitivity represents a major conundrum for the enzyme nitrogenase, as a large fraction of nitrogen-fixing organisms are either obligate aerobes or closely associated with O-respiring organisms to support the high energy demand of catalytic N reduction. To counter O damage to nitrogenase, diazotrophs use O scavengers, exploit compartmentalization or maintain high respiration rates to minimize intracellular O concentrations.

Live-cell imaging of RNA Pol II and elongation factors distinguishes competing mechanisms of transcription regulation.

RNA polymerase II (RNA Pol II)-mediated transcription is a critical, highly regulated process aided by protein complexes at distinct steps. Here, to investigate RNA Pol II and transcription-factor-binding and dissociation dynamics, we generated endogenous photoactivatable-GFP (PA-GFP) and HaloTag knockins using CRISPR-Cas9, allowing us to track a population of molecules at the induced Hsp70 loci in Drosophila melanogaster polytene chromosomes. We found that early in the heat-shock response, little RNA Pol II and DRB sensitivity-inducing factor (DSIF) are reused for iterative rounds of transcription.

Cross-Sectional Survey of Factors Contributing to COVID-19 Testing Hesitancy Among US Adults at Risk of Severe Outcomes from COVID-19.

Introduction: The United States Centers for Disease Control and Prevention (CDC) advises testing individuals for COVID-19 after exposure or if they display symptoms. However, a deeper understanding of demographic factors associated with testing hesitancy is necessary.

Methods: A US nationwide cross-sectional survey of adults with risk factors for developing severe COVID-19 ("high-risk" individuals) was conducted from August 18-September 5, 2023.

Strongyle faecal egg counts in Swiss horses: A retrospective analysis after the introduction of a selective treatment strategy.

The standard parasite management of horses based on regular anthelmintic treatments, now practiced for decades has resulted in a worrying expansion of resistant helminth populations, which may considerably impair control on the farm level. The aim of the present study was to obtain a retrospective (year 2010 - 2016) nationwide analysis of faecal egg count (FEC) data from the Swiss adult horse population, related to horse age and geographic region. Thirteen labs provided a total of 16,387 FEC data of horses aged four to 39 years (average: 13.

A common human MLKL polymorphism confers resistance to negative regulation by phosphorylation.

Across the globe, 2-3% of humans carry the p.Ser132Pro single nucleotide polymorphism in MLKL, the terminal effector protein of the inflammatory form of programmed cell death, necroptosis. Here we show that this substitution confers a gain in necroptotic function in human cells, with more rapid accumulation of activated MLKL in biological membranes and MLKL overriding pharmacological and endogenous inhibition of MLKL.

Computationally Guided Redesign of a Heme-free Cytochrome with Native-like Structure and Stability.

Metals can play key roles in stabilizing protein structures, but ensuring their proper incorporation is a challenge when a metalloprotein is overexpressed in a non-native cellular environment. Here, we have used computational protein design tools to redesign cytochrome (cyt ), which relies on the binding of its heme cofactor to achieve its proper fold, into a stable, heme-free protein. The resulting protein, ApoCyt, features only four mutations and no metal-ligand or covalent bonds, yet displays improved stability over cyt .

Ubiquitylation of RIPK3 beyond-the-RHIM can limit RIPK3 activity and cell death.

Pathogen recognition and TNF receptors signal via receptor interacting serine/threonine kinase-3 (RIPK3) to cause cell death, including MLKL-mediated necroptosis and caspase-8-dependent apoptosis. However, the post-translational control of RIPK3 is not fully understood. Using mass-spectrometry, we identified that RIPK3 is ubiquitylated on K469.

The population of textile fibres on parapets of high-rise housing in Singapore.

A fibre population study was conducted on the parapets (a low wall along the edge of the walkway) of ten housing estates in Singapore. For each location, the ninth and tenth storeys were investigated and a total of 1256 fibres were classified according to colour and generic fibre class. Being a cosmopolitan city with tropical rainforest climate and no true distinct season, the predominant clothing style in Singapore is one that is light, comfortable and modern.

Preference for initiation of end-of-life care discussion in Indonesia: a quantitative study.

Background: Initiating discussion about death and dying is often considered a difficult topic for healthcare providers, thus there is a need for further research to understand this area, particularly in developing countries. The aim of this study was to describe preferences for the initiation of end-of-life care discussions in Indonesia, comparing the general population and health care professionals.

Methods: This cross-sectional, descriptive study analysed quantitative data from 368 respondents to an online questionnaire (255 general population (69%); 113 healthcare professionals (31%)) utilizing consecutive sampling and snowball sampling methods.

In vivo studies on Citrobacter rodentium and host cell death pathways.

Citrobacter rodentium is a mouse-specific extracellular enteropathogen, commonly used as a small animal model for studying human enteropathogenic Escherichia coli infections. Both pathogens share a core set of virulence factors, including a type III secretion system, which enables translocation of effector proteins into infected cells to subvert host antimicrobial responses. Notably, these bacterial effectors have been reported to specifically target components of the apoptotic, necroptotic and pyroptotic signaling cascades in vivo, resulting in compromised immune cell recruitment and impaired mucosal homeostasis.

Association Between Removal of a Warning Against Cephalosporin Use in Patients With Penicillin Allergy and Antibiotic Prescribing.

Importance: Electronic health records (EHRs) often include default alerts that can influence physician selection of antibiotics, which in turn may be associated with a suboptimal choice of agents and increased antibiotic resistance.

Objective: To examine whether removal of a default alert in the EHR to avoid cephalosporin use in patients with penicillin allergies is associated with changes in cephalosporin dispensing or administration in these patients.

Design, Setting, And Participants: This retrospective cohort study of a natural experiment included data on patients who had received antibiotic treatment in the hospital or outpatient setting in 2 regions of a large, integrated health system in California from January 1, 2017, to December 31, 2018.

An acetate-yielding diet imprints an immune and anti-microbial programme against enteric infection.

Objectives: During gastrointestinal infection, dysbiosis can result in decreased production of microbially derived short-chain fatty acids (SCFAs). In response to the presence of intestinal pathogens, we examined whether an engineered acetate- or butyrate-releasing diet can rectify the deficiency of SCFAs and lead to the resolution of enteric infection.

Methods: We tested whether a high acetate- or butyrate-producing diet (HAMSA or HAMSB, respectively) condition infection in mice and assess its impact on host-microbiota interactions.

Metastasis of Lung Adenocarcinoma to the Lacrimal Sac.

The authors report an unusual case of lung adenocarcinoma metastasis to the lacrimal sac. A 61-year-old woman with stage IV non-small cell lung cancer presented with left facial pain and epiphora. She was found to have an elevated tear meniscus associated with a firm, fixed medial canthal mass.

The diverse roles of RIP kinases in host-pathogen interactions.

Receptor Interacting Protein Kinases (RIPKs) are cellular signaling molecules that are critical for homeostatic signaling in both communicable and non-communicable disease processes. In particular, RIPK1, RIPK2, RIPK3 and RIPK7 have emerged as key mediators of intracellular signal transduction including inflammation, autophagy and programmed cell death, and are thus essential for the early control of many diverse pathogenic organisms. In this review, we discuss the role of each RIPK in host responses to bacterial and viral pathogens, with a focus on studies that have used pathogen infection models rather than artificial stimulation with purified pathogen associated molecular patterns.

The association between cigarette smoking, cancer screening, and cancer stage: a prospective study of the women's health initiative observational cohort.

Objective: To assess the dose-dependent relationship between smoking history and cancer screening rates or staging of cancer diagnoses.

Design: Prospective, population-based cohort study.

Setting: Questionnaire responses from the Women's Health Initiative (WHI) Observational Study.

Complete RPE and outer retinal atrophy in patients receiving anti-VEGF treatment for neovascular age-related macular degeneration.

Importance: Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness with several intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents available for its management such as aflibercept, bevacizumab, and ranibizumab. However, direct comparisons between these three agents among the same patient population are limited.

Objective: To assess the rate and growth of complete retinal pigment epithelium and outer retinal atrophy (cRORA) in eyes with nAMD treated with aflibercept, bevacizumab, and/or ranibizumab.

Patient-reported outcomes and quality of life in recessive dystrophic epidermolysis bullosa: A global cross-sectional survey.

Background: A spectrum of skin disease severity exists in patients with recessive dystrophic epidermolysis bullosa (RDEB).

Objective: To characterize the patient-reported outcomes and quality of life (QOL) in patients with RDEB.

Methods: A cross-sectional study of patients with RDEB surveyed through the global EBCare Registry.

Subthreshold laser therapy for macular oedema from branch retinal vein occlusion: focused review.

Retinal vein occlusion is the second-leading cause of vision loss by retinal vascular disease. Subthreshold micropulse laser therapy (SLT) is safer than conventional laser photocoagulation (CLP), yet existing reviews of its use for branch retinal vein occlusion (BRVO) are limited in scope. A literature search of PubMed, Google Scholar, Embase, Cochrane Library and ClinicalTrials.

Association between financial links to indoor tanning industry and conclusions of published studies on indoor tanning: systematic review.

Objective: To assess whether an association exists between financial links to the indoor tanning industry and conclusions of indoor tanning literature.

Design: Systematic review.

Data Sources: PubMed, Embase, and Web of Science, up to 15 February 2019.