Sex-Based Mechanisms of Cardiac Development and Function: Applications for Induced-Pluripotent Stem Cell Derived-Cardiomyocytes.

Males and females exhibit intrinsic differences in the structure and function of the heart, while the prevalence and severity of cardiovascular disease vary in the two sexes. However, the mechanisms of this sex-based dimorphism are yet to be elucidated. Sex chromosomes and sex hormones are the main contributors to sex-based differences in cardiac physiology and pathophysiology. In recent years, the advances in induced pluripotent stem cell-derived cardiac models and multi-omic approaches have enabled a more comprehensive understanding of the sex-specific differences in the human heart. Here, we provide an overview of the roles of these two factors throughout cardiac development and explore the sex hormone signaling pathways involved. We will also discuss how the employment of stem cell-based cardiac models and single-cell RNA sequencing help us further investigate sex differences in healthy and diseased hearts.

Thyroid volume influences serum calcitonin levels in a thyroid-healthy population: results of a 3-assay, 519 subjects study.

BACKGROUND: We aimed to assess determinants for serum calcitonin (CT) levels and to define reference ranges for different CT immunoassays integrating thyroid ultrasonography (TUS) and conventional clinical and biochemical criteria to select the reference population. METHODS: Five hundred and nineteen thyroid-healthy subjects were included in this prospective cross-sectional population study. Thyroid volume was measured by TUS, while serum CT levels were measured by three different immunoassays. RESULTS: Significant interassay differences were found and the agreement between assays was poor. CT levels were higher in males than in females in all immunoassays. Using the first two assays, both gender and thyroid volume were independent determinants for CT levels. While using the third assay, one thyroid volume was the only determinant for CT levels. CONCLUSIONS: Thyroid volume is a relevant determinant for CT levels. In the clinical practice, the difference of the thyroid sizes in males and females warrants gender-specific reference ranges.

Serum thyroglobulin reference values according to NACB criteria in healthy subjects with normal thyroid ultrasound.

BACKGROUND: The present study was undertaken to establish serum thyroglobulin (Tg) normal reference values in a large group of healthy subjects. METHODS: Four hundred and thirty-eight non-smoking healthy subjects were selected to assess the Tg reference values (209 males, 229 non-pregnant females, age 34.7±13.1 years). Inclusion criteria were: no personal or familial history of thyroid disease, thyrotropin levels from 0.5 to 2.00 mUI/L, negative thyroperoxidase and thyroglobulin antibodies. In addition, the patients had a normal size thyroid (females ≤18 mL, males ≤25 mL) without nodules on the thyroid ultrasound (TUS). According to National Academy of Clinical Biochemistry (NACB) criteria the Tg results were transformed to a logarithmic scale and reference ranges were calculated as mean±2 SD. RESULTS: Serum Tg was measured on the Beckman Coulter UniCel DxI 800 automated platform by the simultaneous 1-step immunoenzymatic Access Thyroglobulin assay (Beckmann-Coulter SA, Nyon, Switzerland). Serum Tg levels were higher in females than in males (p=0.0022). Accordingly, gender-specific reference values were calculated (i.e., males: 1.40-29.2 ng/mL; females: 1.50-38.5 ng/mL). CONCLUSIONS: To the best of the authors' knowledge, the first reference interval study for Tg that integrates NACB criteria and TUS assessment for the selection of the reference population is provided here.