Benzimidazole analogues active against adult Schistosoma mansoni: SAR analyses, In vivo efficacy in mice, and preliminary mechanistic studies as potential inhibitors of hemozoin formation.

For over three decades, praziquantel (PZQ) has been the mainstay chemotherapy for prevention and treatment of schistosomiasis. The excessive use of PZQ, coupled with the lack of advanced drug candidates in the current anti-schistosomiasis drug development pipeline, emphasizes the genuine need for new drugs. In the current work, we investigated the antischistosomal potential of a new series of compounds derived from the privileged benzimidazole scaffold, which exhibited low micromolar IC potency in the range of 1.

Collateral damage: the overlooked reproductive health crisis in conflict zones.

Conflict-affected regions face severe reproductive health challenges that disproportionately impact adolescent girls and young women (AGYW) and children, who are especially vulnerable due to the breakdown of healthcare systems and limited access to essential services. AGYW are at heightened risk due to restricted access to family planning, prenatal care, and emergency obstetric services, while children face malnutrition, disease outbreaks, and developmental delays. These challenges have profound long-term consequences for both their physical and psychological well-being.

Returning to Work is Associated with Higher Quality of Life: A LIMB-Q Analysis in Patients with Limb-Threatening Injuries.

Objectives: To identify clinical, demographic, and patient-reported outcomes (PROs) associated with return to work after lower extremity traumatic injury requiring amputation or limb salvage.

Methods: Design: Cross-sectional study.

Setting: Multi-center across 25 countries.

International prevalence patterns of low eGFR in adults aged 18-60 without traditional risk factors from a population-based cross-sectional disadvantaged populations eGFR epidemiology (DEGREE) study.

The disadvantaged populations eGFR (estimated glomerular filtration rate) epidemiology (DEGREE) study was designed to gain insight into the burden of chronic kidney disease (CKD) of undetermined cause (CKDu) using standard protocols to estimate the general-population prevalence of low eGFR internationally. Therefore, we estimated the age-standardized prevalence of eGFR under 60 ml/min per 1.73m in adults aged 18-60, excluding participants with commonly known causes of CKD; an ACR (albumin/creatinine ratio) over 300 mg/g or equivalent, or self-reported or measured (HT) hypertension or (DM) diabetes mellitus, stratified by sex and location.

Eliminating malaria transmission requires targeting immature and mature gametocytes through lipoidal uptake of antimalarials.

Novel antimalarial compounds targeting both the pathogenic and transmissible stages of the human malaria parasite, Plasmodium falciparum, would greatly benefit malaria elimination strategies. However, most compounds affecting asexual blood stage parasites show severely reduced activity against gametocytes. The impact of this activity loss on a compound's transmission-blocking activity is unclear.

Dose-fractionation studies of a phosphatidylinositol 4-kinase inhibitor in a humanized mouse model of malaria.

UCT594 is a 2-aminopyrazine carboxylic acid phosphatidylinositol 4-kinase inhibitor with potent asexual blood-stage activity, the potential for interrupting transmission, as well as liver-stage activities. Herein, we investigated pharmacokinetic/pharmacodynamic (PK/PD) relationships relative to blood-stage activity toward predicting the human dose. Dose-fractionation studies were conducted in the NSG mouse model to determine the PK/PD indices of UCT594, using the minimum parasiticidal concentration as a threshold.

The Tuberculosis Drug Candidate SQ109 and Its Analogs Have Multistage Activity against .

Toward repositioning the antitubercular clinical candidate SQ109 as an antimalarial, analogs were investigated for structure-activity relationships for activity against asexual blood stages of the human malaria parasite pathogenic forms, as well as transmissible, sexual stage gametocytes. We show that equipotent activity (IC) in the 100-300 nM range could be attained for both asexual and sexual stages, with the activity of most compounds retained against a multidrug-resistant strain. The multistage activity profile relies on high lipophilicity ascribed to the adamantane headgroup, and antiplasmodial activity is critically dependent on the diamine linker.

German Translation and Linguistic Validation of the LIMB‑Q: A Patient-reported Outcome Measure for Lower Extremity Trauma.

Background: Lower extremity trauma can have a significant impact on a patient's quality of life. The LIMB-Q is a recently developed and validated patient-reported outcome measure that assesses patient-specific outcomes and experience of health care. The aim of this study was to translate and linguistically validate the LIMB-Q from English to German.

Efficacy of , Isolate ICIPE 7, against , , and spp.

Arthropod vectors are responsible for a multitude of human and animal diseases affecting poor communities in sub-Saharan Africa. Their control still relies on chemical agents, despite growing evidence of insecticide resistance and environmental health concerns. Biorational agents, such as the entomopathogenic fungus , might be an alternative for vector control.

2,8-Disubstituted-1,5-naphthyridines as Dual Inhibitors of Phosphatidylinositol-4-kinase and Hemozoin Formation with Efficacy.

Structure-activity relationship studies of 2,8-disubstituted-1,5-naphthyridines, previously reported as potent inhibitors of () phosphatidylinositol-4-kinase β (PI4K), identified 1,5-naphthyridines with basic groups at 8-position, which retained PI4K inhibitory activity but switched primary mode of action to the host hemoglobin degradation pathway through inhibition of hemozoin formation. These compounds showed minimal off-target inhibitory activity against the human phosphoinositide kinases and MINK1 and MAP4K kinases, which were associated with the teratogenicity and testicular toxicity observed in rats for the PI4K inhibitor clinical candidate MMV390048. A representative compound from the series retained activity against field isolates and lab-raised drug-resistant strains of .

Optimal Treatment Order With Fibula-Free Flap Reconstruction, Oncologic Treatment, and Dental Implants: A Systematic Review and Meta-Analysis.

Head and neck cancer (HNC) patients benefit from craniofacial reconstruction, but no clear guidance exists for rehabilitation timing. This meta-analysis aims to clarify the impact of oncologic treatment order on implant survival. An algorithm to guide placement sequence is also proposed in this paper.

hERG, Life Cycle, and Cross Resistance Profiling of New Azabenzimidazole Analogues of Astemizole.

Toward addressing the cardiotoxicity liability associated with the antimalarial drug astemizole (AST, hERG IC = 0.0042 μM) and its derivatives, we designed and synthesized analogues based on compound ( NF54 IC = 0.012 μM; hERG IC = 0.

Socioeconomic Disparities in Postoperative Outcomes of Osteocutaneous Fibula Free Flaps for Head and Neck Reconstruction.

Background: Osteocutaneous fibula free flaps (FFFs) are a fundamental component of reconstructive surgery in the head and neck region, particularly after traumatic injuries or oncologic resections. Despite their utility, FFFs are associated with various postoperative complications, such as infection, flap failure, and donor site morbidity, impacting up to 54% of cases. This study aimed to investigate the influence of socioeconomic variables, with a particular focus on median household income (MHI), on the incidence of postoperative complications in FFF reconstruction for head and neck cancer.

Complications Following Tissue Expander-Based Reconstruction in Pediatric Burn Injuries: A Retrospective Analysis.

Background: Tissue expansion has been widely used to reconstruct soft tissue defects following burn injuries in pediatric patients, allowing for satisfactory cosmetic and functional outcomes. Factors impacting the success of tissue expander (TE)-based reconstruction in these patients are poorly understood. Herein, we aim to determine the risk factors for postoperative complications following TE-based reconstruction in pediatric burn patients.

Understanding the National Institute for Health and Care Excellence Severity Premium: Exploring Its Implementation and the Implications for Decision Making and Patient Access.

Objectives: This study aimed to evaluate the impact of the National Institute for Health and Care Excellence's (NICE) new severity modifier, which has replaced the end-of-life (EoL) premium, on future NICE recommendations, considering past decision-making patterns.

Methods: NICE technology appraisals (TAs) published between January 2020 and December 2022 were reviewed. Summary statistics were generated to assess how the new severity modifier might affect hypothetical decision making in historical TAs.

Evaluation of the solar-powered Silver Bullet 2.1 (Lumin 8) light trap for sampling malaria vectors in western Kenya.

Background: Centers for Disease Control and Prevention (CDC) light traps are widely used for sampling mosquitoes. However, this trap, manufactured in the USA, poses challenges for use in sub-Saharan Africa due to procurement costs and shipping time. Traps that are equally efficient than the CDC light trap, but which are amenable for use in remote African settings and made in Africa, are desirable to improve local vector surveillance.

A randomized, double-blind placebo-control study assessing the protective efficacy of an odour-based 'push-pull' malaria vector control strategy in reducing human-vector contact.

Novel malaria vector control strategies targeting the odour-orientation of mosquitoes during host-seeking, such as 'attract-and-kill' or 'push-and-pull', have been suggested as complementary tools to indoor residual spraying and long-lasting insecticidal nets. These would be particularly beneficial if they can target vectors in the peri-domestic space where people are unprotected by traditional interventions. A randomized double-blind placebo-control study was implemented in western Kenya to evaluate: a 'push' intervention (spatial repellent) using transfluthrin-treated fabric strips positioned at open eave gaps of houses; a 'pull' intervention placing an odour-baited mosquito trap at a 5 m distance from a house; the combined 'push-pull' package; and the control where houses contained all elements but without active ingredients.

Evaluating Disparities in Pathways to Breast Reconstruction.

Background:  Rates of postmastectomy breast reconstruction have been shown to vary by racial, ethnic, and socioeconomic factors. In this study, we evaluated disparities across pathways toward breast reconstruction.

Methods:  All women who underwent mastectomy for breast cancer at a single institution from 2017 to 2018 were reviewed.

Antimalarial Imidazopyridines Incorporating an Intramolecular Hydrogen Bonding Motif: Medicinal Chemistry and Mechanistic Studies.

We previously identified a novel class of antimalarial benzimidazoles incorporating an intramolecular hydrogen bonding motif. The frontrunner of the series, analogue , showed nanomolar activity against the chloroquine-sensitive NF54 and multi-drug-resistant K1 strains of (NF54 IC = 0.079 μM; K1 IC = 0.