TransLeish: Identification of membrane transporters essential for survival of intracellular Leishmania parasites in a systematic gene deletion screen.

For the protozoan parasite Leishmania, completion of its life cycle requires sequential adaptation of cellular physiology and nutrient scavenging mechanisms to the different environments of a sand fly alimentary tract and the acidic mammalian host cell phagolysosome. Transmembrane transporters are the gatekeepers of intracellular environments, controlling the flux of solutes and ions across membranes. To discover which transporters are vital for survival as intracellular amastigote forms, we carried out a systematic loss-of-function screen of the L.

Exploitation of phylum-spanning omics resources reveals complexity in the nematode FLP signalling system and provides insights into flp-gene evolution.

Background: Parasitic nematodes significantly undermine global human and animal health and productivity. Parasite control is reliant on anthelmintic administration however over-use of a limited number of drugs has resulted in escalating parasitic nematode resistance, threatening the sustainability of parasite control and underscoring an urgent need for the development of novel therapeutics. FMRFamide-like peptides (FLPs), the largest family of nematode neuropeptides, modulate nematode behaviours including those important for parasite survival, highlighting FLP receptors (FLP-GPCRs) as appealing putative novel anthelmintic targets.

A W1282X cystic fibrosis mouse allows the study of pharmacological and gene-editing therapeutics to restore CFTR function.

Background: People with cystic fibrosis carrying two nonsense alleles lack CFTR-specific treatment. Growing evidence supports the hypothesis that nonsense mutation identity affects therapeutic response, calling for mutation-specific CF models. We describe a novel W1282X mouse model and compare it to an existing G542X mouse.

Somatostatin interneuron fate-mapping and structure in a Pten knockout model of epilepsy.

Disruption of inhibitory interneurons is common in the epileptic brain and is hypothesized to play a pivotal role in epileptogenesis. Abrupt disruption and loss of interneurons is well-characterized in status epilepticus models of epilepsy, however, status epilepticus is a relatively rare cause of epilepsy in humans. How interneuron disruption evolves in other forms of epilepsy is less clear.

Smartphone Magnetometers for Assessing Programmable Shunt Valve Settings: A Proof-of-Concept Study.

Background And Objectives: Programmable shunt valves (PSVs) used to treat hydrocephalus require specialized valve-specific devices that determine their setting. However, these devices are typically only accessible in major medical centers. This study explores the feasibility of using smartphone magnetometers to assess PSV settings.

Global analysis of neuropeptide receptor conservation across phylum Nematoda.

Background: The phylum Nematoda is incredibly diverse and includes many parasites of humans, livestock, and plants. Peptide-activated G protein-coupled receptors (GPCRs) are central to the regulation of physiology and numerous behaviors, and they represent appealing pharmacological targets for parasite control. Efforts are ongoing to characterize the functions and define the ligands of nematode GPCRs, with already most peptide GPCRs known or predicted in Caenorhabditis elegans.

Enhanced antifouling and anti-swarming properties poly (sulfobetaine methacrylate-co-2-hydroxy-3-phenoxypropyl acrylate) hydrogel coatings for urinary catheters.

Catheter-associated urinary tract infection (CAUTI) remains an unsolved challenge to date, particularly with the emergence and rapid spread of antimicrobial-resistant bacterial pathogens. Despite extensive research, a catheter coating that can offer intrinsic resistance to host protein deposition, bacterial biofilm formation, and swarming is still urgently required. Zwitterionic hydrogel coatings due to their superior lubricity and antifouling properties represent a promising candidate, but their weak mechanical stability in water and poor resistance to bacterial swarming migration limit their application in urinary catheters for infection control.

When "replicability" is more than just "reliability": The Hubble constant controversy.

We propose that the epistemic functions of replication in science are best understood by relating them to kinds of experimental error/uncertainty. One kind of replication, which we call "direct replications," principally serves to assess the reliability of an experiment through its precision: the presence and degree of random error/statistical uncertainty. The other kind of replication, which we call "conceptual replications," principally serves to assess the validity of an experiment through its accuracy: the presence and degree of systematic errors/uncertainties.

Rationale, design, and participant characteristics of the FAITH! Heart Health+ study: An exploration of the influence of the social determinants of health, stress, and structural racism on African American cardiovascular health.

Background: African Americans (AAs) face cardiovascular health (CVH) disparities linked to systemic racism. The 2020 police killing of Mr. George Floyd in Minneapolis, Minnesota, alongside the COVID-19 pandemic, exacerbated adverse psychosocial factors affecting CVH outcomes among AAs.

Patient-Reported Outcomes From the Phase III HIMALAYA Study of Tremelimumab Plus Durvalumab in Unresectable Hepatocellular Carcinoma.

Purpose: In the phase III HIMALAYA study (ClinicalTrials.gov identifier: NCT03298451) in unresectable hepatocellular carcinoma (uHCC), the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen significantly improved overall survival versus sorafenib, and durvalumab monotherapy was noninferior to sorafenib. Patient-reported outcomes (PROs), a secondary outcome from HIMALAYA, are reported here.

Comparing an Integrated Amphiphilic Surfactant to Traditional Hydrophilic Coatings for the Reduction of Catheter-Associated Urethral Microtrauma.

Hydrophilic-coated intermittent catheters have improved the experience of intermittent urinary catheterization for patients compared to conventional gel-lubricated uncoated catheters. However, the incorporation of polyvinylpyrrolidone (PVP) within hydrophilic coatings can lead to significant issues with coating dry-out. Consequently, increased force on catheter withdrawal may cause complications, including urethral microtrauma and pain.

Infection Is Not Associated With Plasma or Cryoprecipitate Transfusion Volumes in Trauma: A Retrospective Study Using the National Trauma Data Bank.

Packed red blood cell (PRBC) transfusion has been shown to increase nosocomial infection risk in the injured population; however, the post-traumatic infectious risk profiles of non-PRBC blood products are less clear. We hypothesized that plasma (fresh frozen plasma [FFP]), platelet (PLT), and cryoprecipitate administration would not be associated with increased rates of nosocomial infections. We performed a retrospective, matched, case-control study utilizing the American College of Surgeons National Trauma Data Bank data for 2019.

Factors associated with interobserver variation amongst pathologists in the diagnosis of endometrial hyperplasia: A systematic review.

Objective: Reproducible diagnoses of endometrial hyperplasia (EH) remains challenging and has potential implications for patient management. This systematic review aimed to identify pathologist-specific factors associated with interobserver variation in the diagnosis and reporting of EH.

Methods: Three electronic databases, namely MEDLINE, Embase and Web of Science, were searched from 1st January 2000 to 25th March 2023, using relevant key words and subject headings.

A Scanning Tunneling Microscopy Study of the Photoisomerization of Diazocine.

Azobenzenes are fascinating molecular machines that can reversibly transform between two isomeric forms by an external stimulus. Diazocine, a type of bridged azobenzene, has been shown to possess enhanced photoexcitation properties. Due to the distortion caused by the ethyl bridge in the E-isomer, the Z-form becomes the thermodynamically stable configuration.

Transient Seizure Clusters and Epileptiform Activity Following Widespread Bilateral Hippocampal Interneuron Ablation.

Interneuron loss is a prominent feature of temporal lobe epilepsy in both animals and humans and is hypothesized to be critical for epileptogenesis. As loss occurs concurrently with numerous other potentially proepileptogenic changes, however, the impact of interneuron loss in isolation remains unclear. For the present study, we developed an intersectional genetic approach to induce bilateral diphtheria toxin-mediated deletion of Vgat-expressing interneurons from dorsal and ventral hippocampus.

Association and disparities of food insecurity and exposure to violence: analysis of the National Survey of Children's Health.

Context: Lack of access to food is a significant concern for child well-being, and it creates many health disparities and adverse social outcomes. Food insecurity and its many associated risk factors increase parental stress, which are strongly correlated with an increased risk of child abuse and maltreatment. Research now identifies being witness to domestic abuse as a form of child maltreatment, and exposure to violence in the community has been shown to result in similar long-term impacts.

Diffusion of excellence: evaluating a system to identify, replicate, and spread promising innovative practices across the Veterans health administration.

Introduction: The Veterans Health Administration (VHA) Diffusion of Excellence (DoE) program provides a system to identify, replicate, and spread promising practices across the largest integrated healthcare system in the United States. DoE identifies innovations that have been successfully implemented in the VHA through a Shark Tank style competition. VHA facility and regional directors bid resources needed to replicate promising practices.

Bullous Pemphigoid Causing Successive Emergency Department Visits.

Case Presentation: In this case presentation, an 84-year-old male with Fitzpatrick type IV skin tone experienced blistering due to bullous pemphigoid (BP), first on the distal upper left extremity and then on the distal lower extremities, chest, and back. These symptoms resulted in three visits to the emergency department within a month, as well as an episode of hospitalization. Despite treatment, the blistering did not resolve until future outpatient care with dermatology.

The impact of socioeconomic status on health practices via health lifestyles: Results of qualitative interviews with Americans from diverse socioeconomic backgrounds.

We performed 55 qualitative interviews with Americans from diverse socioeconomic backgrounds from a small city in the Northeast to better understand the complex process through which socioeconomic status (SES) influences the health practices persons carry out. We argue that SES not only influences health practices directly, but also via shaping interviewees' health lifestyles. We describe four connected ways that SES shapes interviewees' health lifestyles: (a) the impact of physical and mental illness on how much time, energy, and resources can be devoted to health; (b) the impact of social connections on opportunities to engage in healthy practices; (c) variation in interviewees' sense of control over health and health practices; and (d) how intentional and planned out interviewees' health lifestyles are.

Use of solid thermolytic salts to facilitate microwave-induced in situ amorphization.

Moisture was frequently used as dielectric heating source in classical microwave-able systems to facilitate microwave-induced in situ amorphization, however such systems may face the potential of drug hydrolysis. In this study, solid thermolytic salts were proposed to function as moisture substitutes and their feasibility and impacts on microwave-induced in situ amorphization were investigated. It was found that NHHCO was a promising solid alkaline salt to facilitate both microwave-induced in situ amorphization and in situ salt formation of acidic indomethacin (IND).