Thyroid hormone promotes fetal neurogenesis.

Maternal low thyroxine (T4) serum levels during the first trimester of pregnancy correlate with cerebral cortex volume and mental development of the progeny, but why neural cells during early fetal brain development are vulnerable to maternal T4 levels remains unknown. In this study, using iPSCs obtained from a boy with a loss-of-function mutation in MCT8-a transporter previously identified as critical for thyroid hormone uptake and action in neural cells-we demonstrate that thyroid hormones induce transcriptional changes that promote the progression of human neural precursor cells along the dorsal projection trajectory. Consistent with these findings, single-cell, spatial, and bulk transcriptomics from MCT8-deficient cerebral organoids and cultures of human neural precursor cells underscore the necessity for optimal thyroid hormone levels for these cells to differentiate into neurons.

Lower Serum Triiodothyronine Levels Constitute an Independent Risk Factor for Dyslipidemia in Levothyroxin-Treated Patients.

Objective: Levothyroxine (LT4) is the standard treatment for hypothyroidism; yet many patients show reduced triiodothyronine (T3) levels despite normal thyrotropin (TSH). The clinical impact of the incomplete normalization of T3 homeostasis, including potential metabolic consequences, remains uncertain This study aimed to determine whether lower serum free T3 (FT3) levels in LT4-treated individuals constitute an independent risk factor for dyslipidemia.

Methods: We analyzed data from the Longitudinal Study of Adult Health in Brazil (ELSA-Brasil), which followed 15 105 civil servants aged 35-74 over 3 study waves (2008-2019).

Real-world effectiveness and safety of first-line chemoimmunotherapy combinations in metastatic non-small cell lung cancer with programmed death ligand-1 < 50%: results from an Italian observational study.

Introduction: This multi-center, observational cohort study aimed to evaluate the real-world effectiveness and safety of two first-line chemoimmunotherapy combinations-pembrolizumab plus chemotherapy and nivolumab/ipilimumab plus chemotherapy-in patients with metastatic non-small cell lung cancer (NSCLC) and programmed death ligand-1 (PD-L1) expression < 50%.

Patients And Methods: The primary objectives were progression-free survival (PFS) and overall survival (OS) in the overall population. Secondary objectives included the incidence of chemotherapy-related and immune-related adverse events (irAEs).

Measuring hypothyroidism disease control using a TSH-based "time-in-range".

Context: Time-in-range (TIR) using sequential thyroid stimulating hormone (TSH) levels during levothyroxine (LT4) treatment could serve as a measure of chronic disease control in hypothyroidism.

Objectives: Primary objectives: 1) develop a method of estimating TIR, and 2) determine the impact of patient sociodemographic characteristics on TIR. Secondary objective: investigate the relationship between TIR and time to cardiovascular event.

Treatment of Hypothyroidism that Contains Liothyronine is Associated with Reduced Risk of Dementia and Mortality.

Introduction: Standard levothyroxine (LT4) therapy may not fully address all risks associated with hypothyroidism-especially cognitive decline, dementia, and mortality-even when TSH levels are normalized. Observational studies link hypothyroidism to higher dementia rates; the role of LT4 plus liothyronine (T3) therapies remains uncertain.

Methods: This retrospective cohort study analyzed TriNetX data, comparing 1.

Thyroid Hormone Promotes Fetal Neurogenesis.

Maternal low thyroxine (T4) serum levels during the first trimester of pregnancy correlate with cerebral cortex volume and mental development of the progeny, but why neural cells during early fetal brain development are vulnerable to maternal T4 levels remains unknown. In this study, using iPSCs obtained from a boy with a loss-of-function mutation in MCT8-a transporter previously identified as critical for thyroid hormone uptake and action in neural cells-we demonstrate that thyroid hormones induce transcriptional changes that promote the progression of human neural precursor cells along the dorsal projection trajectory. Consistent with these findings, single-cell, spatial, and bulk transcriptomics from MCT8-deficient cerebral organoids and cultures of human neural precursor cells underscore the necessity for optimal thyroid hormone levels for these cells to differentiate into neurons.

Virtual reality solution to promote adapted physical activity in older adults: outcomes from VR2Care project exploratory study.

Background: Insufficient physical activity is one of the leading risk factors for death worldwide. Regular exercise can improve physical performance and quality of life, reduce the risks of falls and depressive symptoms, and reduce the likelihood of cognitive decline in older adults. Virtual reality (VR) and serious games (SG) are promising tools to improve physical and cognitive functioning.

Overnutrition directly impairs thyroid hormone biosynthesis and utilization, causing hypothyroidism, despite remarkable thyroidal adaptations.

Thyroid hormones (THs: T and T ) are key regulators of metabolic rate and nutrient metabolism. They are controlled centrally and peripherally in a coordinated manner to elegantly match T -mediated energy expenditure (EE) to energy availability. Hypothyroidism reduces EE and has long been blamed for obesity; however, emerging evidence suggests that, instead, obesity may drive thyroid dysfunction.

Praja2 controls P-body assembly and translation in glioblastoma by non-proteolytic ubiquitylation of DDX6.

Glioblastoma multiforme (GBM) is the most lethal form of malignant brain tumor in adults. Dysregulation of protein synthesis contributes to cancer cell plasticity, driving GBM cell heterogeneity, metastatic behavior, and drug resistance. Understanding the complex network and signaling pathways governing protein translation, is therefore an important goal for GBM treatment.

FVB But Not B6 Mice Carrying the Thr92Ala-Dio2 Polymorphism Have Impaired Thyroid Hormonogenesis and Goiter.

The Thr92Ala-Dio2 polymorphism is prevalent worldwide, with about 50% of the population carrying at least 1 allele. The Ala92-Dio2 allele encodes a less active type 2 deiodinase enzyme and has been associated with neurodegenerative diseases, hypertension, and insulin resistance. To understand why its phenotypic effects are variable across different populations, in this study we examined the impact of genetic background on the Thr92Ala-Dio2 polymorphism.

Shared Decisionmaking in the Treatment of Hypothyroidism.

Background: Hypothyroidism, a condition characterized by an underactive thyroid gland, affects millions worldwide, leading to cognitive and metabolic slowdowns. It is most prevalent in women and older adults, with causes including autoimmune thyroiditis, surgical thyroidectomy, and certain medications.

Standard Of Care And Limitations: The standard treatment involves synthetic levothyroxine (LT4) monotherapy, which alleviates symptoms by converting to the active hormone, T3.

Variable transduction of thyroid hormone signaling in structures of the mouse brain.

L-thyroxine (L-T4) monotherapy is the standard treatment for hypothyroidism, administered daily to normalize TSH levels. Once absorbed, T4 is converted to T3 to alleviate most symptoms. However, this treatment abnormally elevates plasma T4 levels in over 50% of patients.

Integrative Protocol for Generation of iPSC-Derived 3D Human Hepatic Organoids.

Obtaining stable hepatic cells in culture poses a significant challenge for liver studies. Bearing this in mind, an optimized method is depicted utilizing human induced pluripotent stem cells (hiPSCs) to generate 3D cultures of human hepatic organoids (HHOs). The utilization of HHOs offers a valuable approach to understanding liver development, unraveling liver diseases, conducting high-throughput studies for drug development, and exploring the potential for liver transplantation.

L-Arginine supplementation as mitochondrial therapy in diabetic cardiomyopathy.

In patients with type II diabetes, the development of diabetic cardiomyopathy (DC) is associated with a high risk of mortality. Left ventricular hypertrophy, diastolic dysfunction, and exercise intolerance are the first signs of DC. The underlying mechanisms are not fully elucidated, and there is an urgent need for specific biomarkers and molecular targets for early diagnosis and treatment.

The Impact of Hypothyroidism on Cardiovascular-Related Healthcare Utilization in the US Population With Diabetes.

Context: Suboptimal treatment of hypothyroidism (HT) is associated with adverse cardiovascular disease (CVD) outcomes, for which patients with diabetes mellitus (DM) are at increased risk.

Objective: This study aimed to compare CVD-related healthcare utilization in DM patients with and without HT in the US population.

Methods: Participant data were collected from the Medical Expenditure Panel Survey (MEPS) over 10 years (2011-2020).

Cardiac involvement in Anderson-Fabry disease. The role of advanced echocardiography.

Anderson-Fabry disease (AFD) is a lysosomal storage disorder, depending on defects in alpha galactosidase A activity, due to a mutation in the galactosidase alpha gene. Cardiovascular involvement represents the leading cause of death in AFD. Cardiac imaging plays a key role in the evaluation and management of AFD patients.

Treatment Preferences in Patients With Hypothyroidism.

Context: Levothyroxine (L-T4) monotherapy is the standard of care for the treatment of hypothyroidism. A minority of L-T4-treated patients remain symptomatic and report better outcomes with combination therapy that contains liothyronine (L-T3) or with desiccated thyroid extract (DTE).

Objective: This work aimed to assess patient preferences in the treatment of hypothyroidism.

Serum parathormone, vitamin D and cardiovascular risk factors and markers: A pilot study.

Background And Aims: Vitamin D deficiency is a common cause of secondary hyperparathyroidism, particularly in elderly people. The aim of this study was to evaluate the associations of serum vitamin D and parathormone (PTH) concentrations with blood pressure values and hypertension-mediated target organ damage (HMOD), including left ventricular (LV) hypertrophy and carotid plaque (CP).

Methods And Results: We enrolled consecutive patients admitted to the Hypertension Center of Federico II University Hospital in Naples, Italy.

The Musashi-1-type 2 deiodinase pathway regulates astrocyte proliferation.

Thyroid hormone (TH) is a critical regulator of cellular function and cell fate. The circulating TH level is relatively stable, while tissue TH action fluctuates according to cell type-specific mechanisms. Here, we focused on identifying mechanisms that regulate TH action through the type 2 deiodinase (D2) in glial cells.

Thr92Ala-DIO2 heterozygosity is associated with skeletal muscle mass and myosteatosis in patients with COVID-19.

Introduction: The type 2 deiodinase and its Thr92Ala-DIO2 polymorphism have been linked to clinical outcomes in acute lung injury and coronavirus disease 2019 (COVID-19).

Objective: The objective was to identify a potential association between Thr92Ala-DIO2 polymorphism and body composition (appendicular muscle mass, myosteatosis, and fat distribution) and to determine whether they reflect the severity or mortality associated with the disease.

Methods: In this prospective cohort study (June-August 2020), 181 patients hospitalized with moderate-to-severe COVID-19 underwent a non-contrast-enhanced computed tomography (CT) of the thorax to assess body composition, laboratory tests, and genotyping for the Thr92Ala-DIO2 polymorphism.

TSH Trajectories During Levothyroxine Treatment in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) Cohort.

Context: Thyroid-stimulating hormone (TSH) trajectory classification represents a novel approach to defining the adequacy of levothyroxine (LT4) treatment for hypothyroidism over time.

Objective: This is a proof of principle study that uses longitudinal clinical data, including thyroid hormone levels from a large prospective study to define classes of TSH trajectories and examine changes in cardiovascular (CV) health markers over the study period.

Methods: Growth mixture modeling (GMM), including latent class growth analysis (LCGA), was used to classify LT4-treated individuals participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) based on serial TSH levels.

Cardiopulmonary determinants of reduced exercise tolerance in Fabry disease.

Fabry disease (FD), also known as Anderson-Fabry disease, is a hereditary disorder of glycosphingolipid metabolism, caused by a deficiency of the lysosomal alpha-galactosidase A enzyme. This causes a progressive accumulation of glycosphingolipids in tissues and organs which represents the main pathogenetic mechanism of FD. The disease is progressive and multisystemic and is characterized by early symptoms and late complications (renal, cardiac and neurological dysfunction).