Androgen receptor drives polyamine synthesis creating a vulnerability for prostate cancer.

Supraphysiological androgen (SPA) treatment can paradoxically restrict growth of castration-resistant prostate cancer with high androgen receptor (AR) activity, which is the basis for use of Bipolar Androgen Therapy (BAT) for patients with this disease. While androgens are widely appreciated to enhance anabolic metabolism, how SPA-mediated metabolic changes alter prostate cancer progression and therapy response is unknown. Here, we report that SPA markedly increased intracellular and secreted polyamines in prostate cancer models.

"Crying in the Wilderness"-The Use of Web-Based Support in Telomere Biology Disorders: Thematic Analysis.

Background: Web-based information and social support are commonly used in rare disease communities where geographic dispersion and limited provider expertise complicate in-person support. We examined web-based resource use among caregivers of individuals with telomere biology disorders (TBDs), which are rare genetic conditions with long diagnostic odysseys and uncertain prognoses including multiorgan system cancer risk.

Objective: This study explored internet-based information-seeking and social support practices and perspectives of patients with TBDs and their caregivers.

Mortality Trends and Causes of Death in Myotonic Dystrophy Type 1 Patients From the UK Clinical Practice Research Datalink.

Introduction/aim: Patients with myotonic dystrophy type1 (DM1) have reduced lifespan. This study aimed to quantify mortality risks, and evaluate causes and time trends in DM1.

Methods: We identified 1021 DM1 patients and 15,104 matched DM1-free controls from the United Kingdom (UK) Clinical Practice Research Datalink.

Foveal avascular zone enlargement correlates with visual acuity decline in patients with diabetic retinopathy.

Purpose: The foveal avascular zone (FAZ) area has been explored as a measure of macular ischemia in diabetic retinopathy (DR) but is limited by its wide variability even in healthy individuals. We hypothesized that FAZ enlargement, which we defined as the difference between the functional FAZ (on optical coherence tomography angiography; OCTA) and structural FAZ (en face OCT), may be a more accurate metric of macular ischemia. In this study, we test the hypothesis that FAZ enlargement is associated with decreased best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) and performs better than the functional FAZ as a marker of vision loss.

A helminth enzyme subverts macrophage-mediated immunity by epigenetic targeting of prostaglandin synthesis.

The molecular mechanisms by which worm parasites evade host immunity are incompletely understood. In a mouse model of intestinal helminth infection using (), we show that helminthic glutamate dehydrogenase (heGDH) drives parasite chronicity by suppressing macrophage-mediated host defense. Combining RNA-seq, ChIP-seq, and targeted lipidomics, we identify prostaglandin E (PGE) as a major immune regulatory mechanism of heGDH.

Progression of Capillary Hypoperfusion in Advanced Stages of Nonproliferative Diabetic Retinopathy: 6-month Analysis of RICHARD Study.

Purpose: To evaluate the 6-month progression of retinal capillary perfusion in eyes with advanced stages of nonproliferative diabetic retinopathy (NPDR).

Design: RICHARD (NCT05112445), 2-year prospective longitudinal study.

Participants: Sixty eyes with Diabetic Retinopathy Severity Scale (DRSS) levels 43, 47, and 53 from 60 patients with type 2 diabetes.

Assessment of Tamarind Seed Polysaccharide (TSP) and Hyaluronic Acid (HA) Containing Ophthalmic Solution to Maintain Tear Osmolarity, Ocular Surface Temperature (OST) and Tear Production.

Background: The enhancement of ocular drug delivery is achieved by using biopolymer carriers in liquid ophthalmic preparations. Using natural polysaccharides to formulate ocular medications is attractive because they are economical and readily available. The primary goal of the study was to assess the safety and effectiveness of Tamarind seed polysaccharide (TSP)/Hyaluronic acid (HA) containing Rohto eye drops (TSP/HA drops) in alleviating the signs and symptoms of dry eye disease (DED) under dry environmental conditions using controlled environmental chamber (CEC).

Intersession repeatability of visual function and OCTA metrics in eyes with diabetic macular ischaemia.

Objective: To estimate inter-session coefficient of repeatability (CR) of visual function and OCTA metrics over 3 months in diabetic macular ischaemia (DMI) in stable laser-treated proliferative diabetic retinopathy (PDR) patients.

Methods: This prospective study recruited patients with stable PDR for at least 6 months following pan-retinal photocoagulation with visual acuity of at least 54 ETDRS letters. DMI was confirmed on OCTA as FAZ area of at least 0.

Macular Capillary Nonperfusion in Eyes With Stable Laser-Treated Proliferative Diabetic Retinopathy.

Importance: Some eyes with proliferative diabetic retinopathy (PDR) treated to stability with panretinal photocoagulation (PRP) continue to lose vision without diabetic macular edema. One presumed cause is macular capillary nonperfusion (CNP)-associated ischemia or infarction. Natural history data of macular CNP might guide treatment trials for it.

Please don't go: retinoic acid 'retains' tissue-specific memory.

Tissue-resident memory (T) T cells not only control infection and cancer, but also contribute to inflammatory disease. In a recent study, Obers et al. demonstrate that retinoic acid (RA) and TGF-β direct T residency in mice, with RA uniquely retaining cells in the intestine by limiting migration.

A "rotating menu" of medical uncertainty for families affected by telomere biology disorders: A qualitative interview study.

Background: Medical uncertainty may cause distress and challenge medical decision-making for patients with rare diseases and their caregivers. Few studies have examined the experience and management of medical uncertainty in rare disease and the dynamics of multiple medical uncertainty sources, issues, and management strategies.

Objective: We explored the experience and management of uncertainty in individuals with telomere biology disorders (TBDs), a set of rare cancer-prone bone marrow failure syndromes, and their caregivers.

Unilateral and bilateral theta burst stimulation for treatment-resistant depression: Follow up on a naturalistic observation study.

Objectives: Theta burst stimulation (TBS) is a novel and faster modality of transcranial magnetic stimulation, which is showing promise as a treatment-resistant depression (TRD) treatment. Though TBS can be applied unilaterally or bilaterally, few studies have compared the effectiveness of both approaches in a naturalistic clinical sample. In this retrospective chart review, we aimed to: (1) replicate previous bilateral sequential TBS effectiveness in a larger cohort of patients at a single centre, (2) present treatment outcome data between unilateral and bilateral TBS approaches, (3) investigate baseline factors associated with our observed outcomes, and (4) examine the sustainability of response, with follow-up data up to 6 months from patients.

Metabolic adaptations of ILC2 and Th2 cells in type 2 immunity.

Type 2 immune responses play a crucial role in host defense against parasitic infections but can also promote the development of allergies and asthma. This response is orchestrated primarily by group 2 innate lymphoid cells (ILC2) and helper type 2 (Th2) cells, both of which undergo substantial metabolic reprogramming as they transition from resting to activated states. Understanding these metabolic adaptations not only provides insights into the fundamental biology of ILC2 and Th2 cells but also opens up potential therapeutic avenues for the identification of novel metabolic targets that can extend the current treatment regimens for diseases in which type 2 immune responses play pivotal roles.

Iodine and Hyperthyroidism: A Double-Edged Sword.

Objective: This article serves as an update to a 1995 review by Braverman and Roti that was publishsed in the inaugural issue of Endocrine Practice.

Methods: We searched PubMed for relevant English-language literature and identified additional papers cited in recent reviews.

Results: Iodine is a trace element found in the Earth's crust that is necessary for the biosynthesis of thyroid hormones.

Glutamine sensing licenses cholesterol synthesis.

The mevalonate pathway produces essential lipid metabolites such as cholesterol. Although this pathway is negatively regulated by metabolic intermediates, little is known of the metabolites that positively regulate its activity. We found that the amino acid glutamine is required to activate the mevalonate pathway.

The impact of a prehospital simulation on medical students' resourcefulness, personal growth initiative, and uncertainty tolerance.

Background: Emergency medicine (EM) physicians often practice in dynamic, high-stress, and uncertain settings with limited resources. Although simulation has been shown to enhance various aspects of student development, its impact on medical students' personal growth initiative, resourcefulness, and tolerance of uncertainty-crucial traits for managing future crises as emergency physicians-remain unclear. The purpose of this study, therefore, was to determine a high-fidelity prehospital simulation's impact on medical students' resourcefulness, personal growth, and tolerance of uncertainty.

A History of the Elimination of Iodine Deficiency Disorders in the Americas: A Dramatic Achievement and Lessons Learned.

Iodine is essential for the synthesis of thyroid hormones, which regulate cell metabolism, growth, and development. Although iodine deficiency (ID) causes adverse health effects across the lifespan, it is particularly problematic in pregnancy, when it can lead to irreversible fetal brain damage. A high prevalence of severe ID, manifesting as endemic goiter and cretinism, predated the arrival of European explorers in the Americas.

Assessing the Quality of Care of Pregnant Patients With Thyrotoxicosis at an Urban Safety Net Hospital.

Objective: Thyrotoxicosis can adversely affect pregnancy. The quality of care (QoC) for thyrotoxicosis in pregnancy at a tertiary care safety net hospital was evaluated based on current guidelines.

Methods: Pregnant patients with thyrotoxicosis or a history of Graves disease who delivered in 2015-2021 were divided into 3 groups: low thyroid stimulating hormone (TSH), active Graves disease, and past Graves disease.

The impact of intravenous versus submucosal dexamethasone on short-term patient response: A randomized controlled trial.

Background: The purpose of this randomized, cross-over trial was to determine if a preoperative dose of dexamethasone administered submucosally is as effective as intravenous (IV) dexamethasone in reducing pain, swelling, and analgesic consumption after periodontal flap surgery.

Methods: Thirty-nine patients planned for two similar flap surgeries under IV sedation were included. Before the first surgery, patients were randomized to receive 8 mg of IV or submucosal dexamethasone.

Comparison of the Diagnosis and Management of Demodex Blepharitis Between Eye Care Practitioners in India and Australasia - A Survey-Based Comparison.

Aim: The primary aim of this study was to compare how eyecare professionals in disparate regions of the world diagnose and manage Demodex blepharitis. A secondary aim was to explore interprofessional differences in diagnostic and management practices.

Methods: Ophthalmologists and optometrists from India and Australia/New Zealand, were invited to complete an online survey on Demodex blepharitis.

A Comparison of Optical Coherence Tomography Angiography Metrics and Artifacts on Scans of Different Sizes in Diabetic Macular Ischemia.

Purpose: Changes in the foveal avascular zone (FAZ) metrics over time are key outcome measures for clinical trials in diabetic macular ischemia (DMI). However, artifacts and automatically delineated FAZ measurements may influence the results. We aimed to compare the artifact frequency and FAZ metrics on 3 × 3 versus 6 × 6 mm optical coherence tomography angiography (OCTA) macular scans in patients with DMI.