Sorafenib Alters Interstitial Proton and Sodium Levels in the Tumor Microenvironment: A H/Na Spectroscopic Imaging Study.

Cellular metabolism is inextricably linked to transmembrane levels of proton (H), sodium (Na), and potassium (K) ions. Although reduced sodium-potassium pump (Na-K ATPase) activity in tumors directly disturbs transmembrane Na and K levels, this dysfunction is a result of upregulated aerobic glycolysis generating excessive cytosolic H (and lactate) which are extruded to acidify the interstitial space. These oncogene-directed metabolic changes, affecting intracellular Na and H, can be further exacerbated by upregulation of ion exchangers/transporters.

Tumor cell-based liquid biopsy using high-throughput microfluidic enrichment of entire leukapheresis product.

Circulating Tumor Cells (CTCs) in blood encompass DNA, RNA, and protein biomarkers, but clinical utility is limited by their rarity. To enable tumor epitope-agnostic interrogation of large blood volumes, we developed a high-throughput microfluidic device, depleting hematopoietic cells through high-flow channels and force-amplifying magnetic lenses. Here, we apply this technology to analyze patient-derived leukapheresis products, interrogating a mean blood volume of 5.

A Multidisciplinary Approach to Navigating Variants of Uncertain Significance in Sudden Infant Deaths: A Case Report of 2 Siblings With an SCN10A VUS.

The sudden death of a previously healthy infant is a devastating event for a family-the death of 2 even more unimaginable. Prior to the debunking of Meadow's law, a legal concept attributing multiple unexplained infant deaths to Munchausen by proxy, these events could lead to the wrongful prosecution of those who had lost their children to "sudden unexpected infant death (SUID)." Today, these cases, wherein multiple infants within one family pass inexplicably, raise suspicion for a possible genetic cause and point toward a need for postmortem genetic testing.

Associations between subclinical thyroid dysfunction and cardiovascular risk factors according to age and sex.

Context: Subclinical thyroid dysfunction (ScTD) comprising subclinical hypothyroidism (SHypo) and subclinical hyperthyroidism (SHyper) has been associated with increased risk for cardiovascular events.

Objective: To assess associations between ScTD and cardiovascular risk factors (cvRFs) according to age and sex.

Design And Setting: Pooled individual participant data analysis of large prospective cohort studies from the Thyroid Studies Collaboration.

Effect of correcting iron deficiency on the risk of serious infection in heart failure: Insights from the IRONMAN trial.

Aims: Concerns exist that intravenous (IV) iron might increase the risk of infections. The IRONMAN trial provided an opportunity to investigate whether giving IV ferric derisomaltose (FDI) to patients with heart failure and iron deficiency alters the rate of hospitalization or death due to infections.

Methods And Results: IRONMAN was a randomized trial of IV FDI versus usual care in patients with symptomatic heart failure, left ventricular ejection fraction (LVEF) ≤45%, and transferrin saturation (TSAT) <20% or ferritin <100 μg/L.

Longitudinal associations of DXA-measured visceral adipose tissue and cardiometabolic risk in middle-to-older aged adults.

Background And Aims: DXA-measured visceral adipose tissue (VAT) is associated with adverse cardiometabolic risk profiles in cross-sectional studies, but longitudinal associations have not been investigated. We examined the longitudinal associations of baseline and change in VAT with future cardiometabolic risk in Australian participants of the Busselton Healthy Ageing study.

Methods And Results: We studied 3569 participants (54.

Defining Gestational Thyroid Dysfunction Through Modified Nonpregnancy Reference Intervals: An Individual Participant Meta-analysis.

Background: Establishing local trimester-specific reference intervals for gestational TSH and free T4 (FT4) is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific nonpregnancy reference intervals as compared to trimester-specific reference intervals.

Methods: We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy.

Decompression and collagen wrapping of a fibrolipomatous hamartoma of the median nerve: a new approach for a rare and difficult problem.

Fibrolipomatous hamartoma is a rare benign slow growing fibrofatty tumor of peripheral nerves of unknown etiology. Clinical presentation may mimic carpal tunnel syndrome when involving the median nerve. We present a case of FLH of the median nerve in a 59-year-old female treated with decompression and collagen nerve wrapping.

Connectome-driven neural inventory of a complete visual system.

Vision provides animals with detailed information about their surroundings, conveying diverse features such as color, form, and movement across the visual scene. Computing these parallel spatial features requires a large and diverse network of neurons, such that in animals as distant as flies and humans, visual regions comprise half the brain's volume. These visual brain regions often reveal remarkable structure-function relationships, with neurons organized along spatial maps with shapes that directly relate to their roles in visual processing.

Tumor cell-based liquid biopsy using high-throughput microfluidic enrichment of entire leukapheresis product.

Circulating Tumor Cells (CTCs), interrogated by sampling blood from patients with cancer, contain multiple analytes, including intact RNA, high molecular weight DNA, proteins, and metabolic markers. However, the clinical utility of tumor cell-based liquid biopsy has been limited since CTCs are very rare, and current technologies cannot process the blood volumes required to isolate a sufficient number of tumor cells for in-depth assays. We previously described a high-throughput microfluidic prototype utilizing high-flow channels and amplification of cell sorting forces through magnetic lenses.

A review of sources of resistance to turnip yellows virus (TuYV) in species.

Turnip yellows virus (TuYV; previously known as beet western yellows virus) causes major diseases of species worldwide resulting in severe yield-losses in arable and vegetable crops. It has also been shown to reduce the quality of vegetables, particularly cabbage where it causes tip burn. Incidences of 100% have been recorded in commercial crops of winter oilseed rape () and vegetable crops (particularly ) in Europe.

Use of thyroid hormones in hypothyroid and euthyroid patients: A survey of members of the Endocrine Society of Australia.

Objective: Hypothyroidism is a common endocrine condition usually managed with levothyroxine (LT4). However, controversy remains around the use of liothyronine (LT3). We aimed to investigate the practices of Australian endocrinologists when managing patients with hypothyroidism, their use of LT3 + LT4 combination therapy and use of thyroid hormones in euthyroid patients.

Fatal Case of Exercise Collapse Associated with Sickle Cell Trait with Novel Underlying LAMA2 Mutation.

Sickle cell trait is typically thought to be an asymptomatic carrier state, but it is rarely associated with exertional rhabdomyolysis in cases termed Exercise Collapse Associated with Sickle Cell Trait (ECAST). In a subset of these cases, underlying disease contributes to the development and/or severity of the ensuing medical complications. We describe the first ever case of ECAST reported in a previously asymptomatic, multiply deployed, highly physically active service member with an underlying heterozygous LAMA2 mutation.

Conversion of First Metatarsal-Phalangeal Joint Arthrodesis to Arthroplasty: A Case Report.

Introduction: Arthrodesis remains the gold standard for most first metatarsal-phalangeal joint (1MTPJ) pathologic conditions due to its high patient satisfaction, low complication rates, and consistent data. 1MTPJ arthroplasty remains a pursued procedure given the advantages described above, but the literature remains complicated and controversial as a primary surgical treatment. To the authors' knowledge, there is no prior report describing utilization of arthroplasty as an approach to managing clinical failure of a successful fusion in the setting of a technically successful procedure without a post-operative complication.

Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget's disease of bone.

Introduction: Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment.

Methods: We randomised 222 individuals at increased risk of PDB because of pathogenic variants to receive 5 mg zoledronic acid (ZA) or placebo.

Age-dependent genetic regulation of osteoarthritis: independent effects of immune system genes.

Objectives: Osteoarthritis (OA) is a joint disease with a heritable component. Genetic loci identified via genome-wide association studies (GWAS) account for an estimated 26.3% of the disease trait variance in humans.