Excitoprotective effects of conditional tau reduction in excitatory neurons and in adulthood.

Unlabelled: Tau reduction is a promising therapeutic strategy for Alzheimer's disease. In numerous models, tau reduction via genetic knockout is beneficial, at least in part due to protection against hyperexcitability and seizures, but the underlying mechanisms are unclear. Here we describe the generation and initial study of a new conditional Tau model to address these mechanisms.

GRK5 is required for adipocyte differentiation through ERK activation.

Previous studies have identified G protein-coupled receptor (GPCR) kinase 5 (GRK5) as a genetic factor contributing to obesity pathogenesis, but the underlying mechanism remains unclear. We demonstrate here that Grk5 mRNA is more abundant in stromal vascular fractions of mouse white adipose tissue, the fraction that contains adipose progenitor cells, or committed pre-adipocytes, than in adipocyte fractions. Thus, we generated a GRK5 knockout (KO) 3T3-L1 pre-adipocyte to further investigate the mechanistic role of GRK5 in regulating adipocyte differentiation.

Monoclonal gammopathy in the setting of Pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterized by ulcerative painful lesions with violaceous undermined borders. Up to 75% of PG cases develop in association with an underlying systemic disease. Monoclonal gammopathy is reportedly a concomitant condition with PG, with studies indicating immunoglobulin (Ig) A gammopathy as the most common.

1,25-Dihydroxyvitamin D Suppresses Prognostic Survival Biomarkers Associated with Cell Cycle and Actin Organization in a Non-Malignant African American Prostate Cell Line.

Vitamin D is a steroid hormone that confers anti-tumorigenic properties in prostate cells. Serum vitamin D deficiency has been associated with advanced prostate cancer (PCa), particularly affecting African American (AA) men. Therefore, elucidating the pleiotropic effects of vitamin D on signaling pathways, essential to maintaining non-malignancy, may provide additional drug targets to mitigate disparate outcomes for men with PCa, especially AA men.

The I-PREDICT 50th Percentile Male Warfighter Finite Element Model: Development and Validation of the Thoracolumbar Spine.

Military personnel are commonly at risk of lower back pain and thoracolumbar spine injury. Human volunteers and postmortem human subjects have been used to understand the scenarios where injury can occur and the tolerance of the warfighter to these loading regimes. Finite element human body models (HBMs) can accurately simulate the mechanics of the human body and are a useful tool for understanding injury.

Characterising 24-h skeletal muscle gene expression alongside metabolic & endocrine responses under diurnal conditions.

Context: Skeletal muscle plays a central role in the storage, synthesis, and breakdown of nutrients, yet little research has explored temporal responses of this human tissue, especially with concurrent measures of systemic biomarkers of metabolism.

Objective: To characterise temporal profiles in skeletal muscle expression of genes involved in carbohydrate metabolism, lipid metabolism, circadian clocks, and autophagy and descriptively relate them to systemic metabolites and hormones during a controlled laboratory protocol.

Methods: Ten healthy adults (9M/1F, mean ± SD: age: 30 ± 10 y; BMI: 24.

Using mHealth to reduce disparities in Black maternal health: Perspectives from Black rural postpartum mothers.

Background: Racial disparities are evident in maternal morbidity and mortality rates globally. Black women are more likely to die from pregnancy and childbirth than any other race or ethnicity. This leaves one of the largest gaps in women's health to date.

Dose escalation of biologic treatment in patients with moderate-to-severe psoriasis in Japan.

Patients receiving interleukin (IL)-inhibiting biologics for moderate-to-severe psoriasis (PsO) may be treated with escalated doses to optimize outcomes. This study evaluated escalation prevalence in a Japanese claims analysis of patients with PsO diagnosis preceding IL-inhibiting biologic treatment and ≥1 post-induction maintenance claim (index date) with sufficient data availability from January 2014 to May 2022. Patients with non-persistence were excluded.

Autocalibration based on dilution of a single concentrated standard is used for the determination of silicate in sea water by the modified molybdenum blue method.

The silicate (Si) molybdenum blue method was modified by combining oxalate and ascorbic acid into a single reagent and was used for determining Si in sea water samples. The first step of this automated assay protocol was designed to perform either a calibration by a single Si standard prepared in deionized (DI) water, or to dilute samples in the range of 0-160 μM Si to fit into 0-20 μM Si calibration range using a 20 cm flow cell. By designing the assay protocol to function in batch mode, the influence of salinity on calibration was eliminated, thus making the method suitable for analysis of samples collected in the open ocean, coastal areas, or rivers.

2024 CSANZ Position Statement on Indications, Assessment and Monitoring of Structural and Valvular Heart Disease With Transthoracic Echocardiography in Adults.

Transthoracic echocardiography (TTE) is the most widely available and utilised imaging modality for the screening, diagnosis, and serial monitoring of all abnormalities related to cardiac structure or function. The primary objectives of this document are to provide (1) a guiding framework for treating clinicians of the acceptable indications for the initial and serial TTE assessments of the commonly encountered cardiovascular conditions in adults, and (2) the minimum required standard for TTE examinations and reporting for imaging service providers. The main areas covered within this Position Statement pertain to the TTE assessment of the left and right ventricles, valvular heart diseases, pericardial diseases, aortic diseases, infective endocarditis, cardiac masses, pulmonary hypertension, and cardiovascular diseases associated with cancer treatments or cardio-oncology.

Oxidative Stress is a shared characteristic of ME/CFS and Long COVID.

More than 65 million individuals worldwide are estimated to have Long COVID (LC), a complex multisystemic condition, wherein patients of all ages report fatigue, post-exertional malaise, and other symptoms resembling myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). With no current treatments or reliable diagnostic markers, there is an urgent need to define the molecular underpinnings of these conditions. By studying bioenergetic characteristics of peripheral blood lymphocytes in over 16 healthy controls, 15 ME/CFS, and 15 LC, we find both ME/CFS and LC donors exhibit signs of elevated oxidative stress, relative to healthy controls, especially in the memory subset.

A high dose KRP203 induces cytoplasmic vacuoles associated with altered phosphoinositide segregation and endosome expansion.

In animal cells, vacuoles are absent, but can be induced by diseases and drugs. While phosphoinositides are critical for membrane trafficking, their role in the formation of these vacuoles remains unclear. The immunosuppressive KRP203/Mocravimod, which antagonizes sphingosine-1-phosphate receptors, has been identified as having novel multimodal activity against phosphoinositide kinases.

Stakeholder Perceptions of Animal Welfare as a Component of Sustainable Beef Programs in the United States-A Pilot Study.

This study aimed to investigate how stakeholders in the United States beef industry incorporate animal welfare into their sustainability programs. A survey was administered online to the U.S.

Epigenetic Priming by Hypomethylation Enhances the Immunogenic Potential of Tolinapant in T-cell Lymphoma.

Unlabelled: Programmed cell death mechanisms are important for the regulation of tumor development and progression. Evasion of and resistance to apoptosis are significant factors in tumorigenesis and drug resistance. Bypassing apoptotic pathways and eliciting another form of regulated cell death, namely necroptosis, an immunogenic cell death (ICD), may override apoptotic resistance.

Conversion ratios: Why is it so challenging to construct opioid conversion tables?

Standardizing opioid management is challenging due to the absence of a ceiling dose, the unknown ideal therapeutic plasma level, and the lack of an clear relationship between dose and therapeutic response. Opioid rotation or conversion, which is switching from one opioid, route of administration, or both, to another, to improve therapeutic response and reduce toxicities, occurs in 20-40 percent of patients treated with opioids. Opioid conversion is often needed when there are adverse effects, toxicities, or inability to tolerate a certain opioid formulation.

POLR3A-related disorders: From spastic ataxia to generalised dystonia and long-term efficacy of deep brain stimulation.

While biallelic POLR3A loss-of-function variants are traditionally linked to hypomyelinating leukodystrophy, patients with a specific splice variant c.1909+22G>A manifest as adolescent-onset spastic ataxia without overt leukodystrophy. In this study, we reported eight new cases, POLR3A-related disorder with c.

Male elephant management in AZA institutions: Current status and priorities for the future.

Asian elephant (Elephas maximus) and African savanna elephant (Loxodonta africana) populations collectively managed by ex-situ facilities accredited by the Association of Zoos and Aquariums (AZA) face sustainability challenges. Among the priorities to strengthen animal wellbeing and population sustainability is male elephant management. We conducted a survey of AZA facilities currently housing male elephants to assess the status, challenges, and priorities in three areas of male elephant management: musth, socialization, and semen collection.

SNAPSHOT USA 2021: A third coordinated national camera trap survey of the United States.

SNAPSHOT USA is a multicontributor, long-term camera trap survey designed to survey mammals across the United States. Participants are recruited through community networks and directly through a website application (https://www.snapshot-usa.

A Biomimetic Leaflet Scaffold for Aortic Valve Remodeling.

Heart valve disease poses a significant clinical challenge, especially in pediatric populations, due to the inability of existing valve replacements to grow or respond biologically to their microenvironment. Tissue-engineered heart valves (TEHVs) provide a solution by facilitating patient-specific models for self-repair and remodeling. In this study, a 3D-bioprinted TEHV is designed to emulate the trilayer leaflet structure of an aortic valve.