Small molecule APOL1 inhibitors as a precision medicine approach for APOL1-mediated kidney disease.

Chronic kidney disease affects ~10% of people worldwide and there are no disease modifying therapeutics that address the underlying cause of any form of kidney disease. Genome wide association studies have identified the G1 and G2 variants in the apolipoprotein L1 (APOL1) gene as major contributors to a subtype of proteinuric kidney disease now referred to as APOL1-mediated kidney disease (AMKD). We hypothesized that inhibition of APOL1 could have therapeutic potential for this genetically-defined form of kidney disease.

Aeromedical evacuation-relevant hypobaria following traumatic brain injury in rats contributes to cerebral blood flow depression, altered neurochemistry, and increased neuroinflammation.

Aircraft cabins are routinely pressurized to the equivalent of 8000 ft altitude. Exposure of lab animals to aeromedical evacuation relevant hypobaria after traumatic brain injury worsens neurological outcomes, which is paradoxically exacerbated by hyperoxia. This study tested the hypothesis that exposure of rats to hypobaria following cortical impact reduces cerebral blood flow, increases neuroinflammation, and alters brain neurochemistry.

Behavioral assessment of well-being in the naïve laboratory ferret (Mustela putorius furo).

Domestic ferrets (Mustela putorius furo) are an emerging model species in biomedical research. While behavioral studies are a critical translational tool for evaluating neurologic function in disease models and toxicology studies, there is a lack of ferret-specific behavioral assays and corresponding data on baseline behavior. Play behavior is a promising target for evaluation of psychological well-being, particularly because ferrets engage in solitary and social play well into adulthood.

Clinical study design strategies to mitigate confounding effects of time-dependent clearance on dose optimization of therapeutic antibodies.

Time-dependent pharmacokinetics (TDPK) is a frequent confounding factor that misleads exposure-response (ER) analysis of therapeutic antibodies, where a decline in clearance results in increased drug exposure over time in patients who respond to therapy, causing a false-positive ER finding. The object of our simulation study was to explore the influence of clinical trial designs on the frequency of false-positive ER findings. Two previously published population PK models representative of slow- (pembrolizumab) and fast-onset (rituximab) TDPK were used to simulate virtual patient cohorts with time-dependent clearance and the frequency of false-positive ER findings.

Warm temperature inhibits cytoplasmic incompatibility induced by endosymbiotic Rickettsiella in spider hosts.

Bacterial endosymbionts manipulate reproduction in arthropods to increase their prevalence in the host population. One such manipulation is cytoplasmic incompatibility (CI), wherein the bacteria sabotage sperm in infected males to reduce the hatch rate when mated with uninfected females, but zygotes are 'rescued' when that male mates with an infected female. In the spider Mermessus fradeorum (Linyphiidae), Rickettsiella symbionts cause variable levels of CI.

Generally applicable physics-based equation of state for liquids.

Physics-based first-principles pressure-volume-temperature equations of state (EOS) exist for solids and gases but not for liquids due to the long-standing fundamental problems involved in liquid theory. Current EOS models that are applicable to liquids and supercritical fluids at liquid-like density under conditions relevant to planetary interiors and industrial processes are complex empirical models with many physically meaningless adjustable parameters. Here, we develop a generally applicable physics-based (GAP) EOS for liquids including supercritical fluids at liquid-like density.

Could primary care records be used to identify women at risk of perinatal anxiety? A mixed-methods study.

Background: Perinatal anxiety (PNA) occurs throughout the antenatal period or up to 1 year after childbirth, with a prevalence of 21%.

Aim: To investigate if primary care records could be used to identify women at 'higher risk' of PNA.

Method: Mixed-methods approach using quantitative and qualitative methods.

How can we improve support for women with perinatal anxiety in primary care? A qualitative study.

Background: Perinatal anxiety (PNA) occurs during pregnancy and up to 12 months post-partum. PNA affects more than 21% of women and can impact adversely on mothers, children and their families. National Institute for Health and Care Excellence (NICE) guidance identified evidence gaps around non-pharmacological interventions for PNA.

Utilizing gas flux from automated head chamber systems to estimate dietary energy values for beef cattle fed a finishing diet.

Dietary net energy for maintenance (NEm) and gain (NEg) can be estimated using calculations based on live performance or adjusted-final body weight, which is calculated based on carcass characteristics. These values are commonly referred to as performance-adjusted (pa) NEm (paNEm) and NEg (paNEg). The NEm and NEg of a diet can also be estimated by adding recovered energy (RE) with heat production (HP) derived from an automated head chamber system (AHCS), which we will term gas-adjusted (ga) NEm (gaNEm) and NEg (gaNEg).

Recommendations on visit duration and sample number requirements for an automated head chamber system.

Automated head chamber systems (AHCS; GreenFeed, C-Lock Inc., Rapid City, SD) increasingly are being used for measuring the gas flux of unrestrained cattle. There are a wide range of recommendations for what constitutes a "good" visit (i.

A TriAdj-Adjuvanted CPAF Protein Vaccine Is Highly Immunogenic in Pigs.

() infections are the most common sexually transmitted infection (STI). Despite effective antibiotics for , undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as () in pigs.

Prison Health Care Issues in Kansas and Ohio: The Perspective of Incarcerated Women.

This article about women's prison-based health care reports quantitative findings from surveying 206 female prisoners and qualitative findings from 45 female prisoners interviewed in one prison in Kansas and three prisons in Ohio. Respondents expressed concerns about the availability of quality prison health care and the timeliness of attention to requests for assistance. Additionally, respondents identified administrative barriers to receiving quality health care within each state.

Expanding the possible: exploring the role for heterodox economics in integrated climate-economy modeling.

This paper explores the degree to which heterodox economics can contribute to the development and use of climate-economy integrated assessment models. To do so, it introduces the field of integrated assessment modeling, with a focus on the core economic methodology used by various types of models. It then summarizes some of the literature critiquing these models and how they inform policy.

Quantifying changes in individual-specific template-based representations of center-of-mass dynamics during walking with ankle exoskeletons using Hybrid-SINDy.

Ankle exoskeletons alter whole-body walking mechanics, energetics, and stability by altering center-of-mass (CoM) motion. Controlling the dynamics governing CoM motion is, therefore, critical for maintaining efficient and stable gait. However, how CoM dynamics change with ankle exoskeletons is unknown, and how to optimally model individual-specific CoM dynamics, especially in individuals with neurological injuries, remains a challenge.

Pentosan polysulfate and a pigmentary maculopathy: causation versus correlation?

Introduction: Interstitial cystitis (IC) is a chronic disease with urinary tract symptoms and pain. Pentosan polysulfate (PPS) is the only U.S.

Evaluating the performance of Plasmodium falciparum genetics for inferring National Malaria Control Program reported incidence in Senegal.

Genetic surveillance of the parasite shows great promise for helping National Malaria Control Programs (NMCPs) assess parasite transmission. Genetic metrics such as the frequency of polygenomic (multiple strain) infections, genetic clones, and the complexity of infection (COI, number of strains per infection) are correlated with transmission intensity. However, despite these correlations, it is unclear whether genetic metrics alone are sufficient to estimate clinical incidence.

Malaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal.

We here analyze data from the first year of an ongoing nationwide program of genetic surveillance of Plasmodium falciparum parasites in Senegal. The analysis is based on 1097 samples collected at health facilities during passive malaria case detection in 2019; it provides a baseline for analyzing parasite genetic metrics as they vary over time and geographic space. The study's goal was to identify genetic metrics that were informative about transmission intensity and other aspects of transmission dynamics, focusing on measures of genetic relatedness between parasites.

Time-dependent clearance can confound exposure-response analysis of therapeutic antibodies: A comprehensive review of the current literature.

Exposure-response (ER) analysis is used to optimize dose and dose regimens during clinical development. Characterization of relationships between drug exposure and efficacy or safety outcomes can be utilized to make dose adjustments that improve patient response. Therapeutic antibodies typically show predictable pharmacokinetics (PK) but can exhibit clearance that decreases over time due to treatment.

An Experimental Field Trial Investigating the Use of Bacteriophage and Manure Slurry Applications in Beef Cattle Feedlot Pens for Mitigation.

Post-harvest mitigation techniques are insufficient at addressing harbored in cattle lymph nodes, necessitating the exploration of pre-harvest alternatives that reduce prior to dissemination to the lymph nodes. A 2 × 2, unbalanced experiment was conducted to determine the effectiveness of pre-harvest treatments applied to the pen surface for mitigation in cattle. Treatments included manure slurry intended to mimic pen run-off water (n = 4 pens), a bacteriophage cocktail (n = 4), a combination of both treatments (n = 5), and a control group (n = 5) that received no treatment.

Qualitative Analysis of Patient Experiences Reaching Urethroplasty for Recurrent Urethral Stricture Disease.

Purpose: Despite the inferior outcomes, urethral stricture patients often undergo multiple endoscopic procedures prior to undergoing definitive urethroplasty. We sought to qualitatively evaluate the patient experience of obtaining urethroplasty to better understand the impact of this experience on quality of life.

Materials And Methods: Patients treated with urethroplasty between September 2019 and July 2021 were identified and invited to participate in our study if they had undergone ≥ 2 endoscopic procedures prior to urethroplasty.

Sampling for malaria molecular surveillance.

Strategic use of Plasmodium falciparum genetic variation has great potential to inform public health actions for malaria control and elimination. Malaria molecular surveillance (MMS) begins with a strategy to identify and collect parasite samples, guided by public-health priorities. In this review we discuss sampling design practices for MMS and point out epidemiological, biological, and statistical factors that need to be considered.

Rationale and design of an implant procedure and pivotal study to evaluate safety and effectiveness of Medtronic's tibial neuromodulation device.

Percutaneous tibial neuromodulation is a medical guideline recommended therapy for treating symptoms of overactive bladder. Stimulation is delivered to the tibial nerve via a thin needle placed percutaneously for 30 min once a week for 12-weeks, and monthly thereafter. Studies have shown that this therapy can effectively relieve symptoms of overactive bladder; however, the frequent office visits present a barrier to patients and can impact therapy effectiveness.

Contraceptive Adoption and Changes in Empowerment in Kenya, Nigeria, and Senegal.

Women's empowerment and contraceptive use are critical to achieving gender equality. The positive association between more empowered women and higher rates of contraceptive use has been well-established by cross-sectional research. However, there remains a gap in understanding the longitudinal relationship between contraceptive adoption and changes to women's empowerment.