Higher bone mineral density in Caucasian, hirsute patients of reproductive age. Positive correlation of testosterone levels with bone mineral density in hirsutism

OBJECTIVE: The mechanisms leading to higher bone mineral density (BMD) in hirsute patients than in healthy controls have seldom been examined. We compared the metabolic, hormonal and bone metabolic parameters in hirsute patients and female controls and correlated BMD and bone metabolic parameters with testosterone, oestradiol and metabolic parameters. PATIENTS: Fifty-one Caucasian, reproductive-aged, hirsute patients referred to the outpatient clinic of an academic tertiary-care medical centre and 63 healthy, female Caucasian controls matched for season, weight and age. MEASUREMENTS: BMD (hip, neck, lumbar and total BMD), bone metabolic parameters (osteocalcin, alkaline phosphatase, PTH, ionized calcium, phosphate and 25-hydroxyvitamin D (25OHD)) and endocrine profiles (androgen status, oestradiol and insulin) were evaluated during follicular phase. Oestradiol measurement was repeated during cycle days 8-12. RESULTS: Lumbar and neck BMD levels were significantly higher in hirsute patients than in controls: (mean +/- SD): lumbar BMD 1.10 +/- 0.12 vs. 1.06 +/- 0.10 g/cm2 and neck BMD 0.91 +/- 0.11 vs. 0.87 +/- 0.12 g/cm2, P < 0.05. Fasting insulin and free testosterone levels were significantly higher in hirsute patients than in controls. Free testosterone correlated positively with neck and hip BMD levels in hirsute patients. During multiple regression analysis, testosterone, oestradiol and waist/hip ratio (WHR) were found to have positive effects on BMD levels independent of body mass index (BMI). 25OHD levels were significantly lower in hirsute patients [42 (13-131)] than in controls [72 (27-196)] nmol/l (geometric mean +/- 2SD), P < 0.001]. CONCLUSION: Hirsute patients demonstrated significantly higher bone mineral density levels than controls, which could be explained by hyperinsulinaemia and higher testosterone levels in hirsute patients compared with controls. The pathogenesis for significantly lower 25-hydroxyvitamin D levels in hirsute patients compared with controls needs to be evaluated in future studies.     

Dynamic Modeling of Cost-effectiveness of Rotavirus Vaccination,Kazakhstan

The government of Kazakhstan, a middle-income country in Central Asia, is considering the introduction of rotavirus vaccination into its national immunization program. We performed a cost-effectiveness analysis of rotavirus vaccination spanning 20 years by using a synthesis of dynamic transmission models accounting for herd protection. We found that a vaccination program with 90% coverage would prevent ≈880 rotavirus deaths and save an average of 54,784 life-years for children <5 years of age. Indirect protection accounted for 40% and 60% reduction in severe and mild rotavirus gastroenteritis, respectively. Cost per life year gained was US $18,044 from a societal perspective and US $23,892 from a health care perspective. Comparing the 2 key parameters of cost-effectiveness, mortality rates and vaccine cost at <US $2.78 per dose, vaccination program costs would be entirely offset. To further evaluate efficacy of a vaccine program, benefits of indirect protection conferred by vaccination warrant further study.     

Low Seroprevalence among Undetected COVID-19 Cases,Faroe Islands,November 2020

We conducted a second nationwide severe acute respiratory syndrome coronavirus 2 seroprevalence study in the Faroe Islands during November 2020. We found crude seroprevalence was 0.3% and prevalence was 0.4% after adjusting for test sensitivity and specificity. This low seroprevalence supports the prevention strategies used in the Faroe Islands.     

Unique and redundant roles of SOX2 and SOX17 in regulating the germ cell tumor fate

Embryonal carcinomas (ECs) and seminomas are testicular germ cell tumors. ECs display expression of SOX2, while seminomas display expression of SOX17. In somatic differentiation, SOX17 drives endodermal cell fate. However, seminomas lack expression of endoderm markers, but show features of pluripotency. Here, we use chromatin immunoprecipitation sequencing to report and compare the binding pattern of SOX17 in seminoma-like TCam-2 cells to SOX17 in somatic cells and SOX2 in EC-like 2102EP cells. In seminoma-like cells, SOX17 was detected at canonical (SOX2/OCT4), compressed (SOX17/OCT4) and noncomposite SOX motifs. SOX17 regulates TFAP2C, PRDM1 and PRDM14, thereby maintaining latent pluripotency and suppressing somatic differentiation. In contrast, in somatic cells canonical motifs are rarely bound by SOX17. In sum, only 12% of SOX17-binding sites overlap in seminoma-like and somatic cells. This illustrates that binding site choice is highly dynamic and cell type specific. Deletion of SOX17 in seminoma-like cells resulted in loss of pluripotency, marked by a reduction of OCT4 protein level and loss of alkaline phosphatase activity. Furthermore, we found that in EC-like cells SOX2 regulates pluripotency-associated genes, most likely by partnering with OCT4. In conclusion, SOX17 (in seminomas) functionally replaces SOX2 (in ECs) to maintain expression of the pluripotency cluster.