Unraveling the evolutionary origin of the complex Nuclear Receptor Element (cNRE), a cis-regulatory module required for preferential expression in the atrial chamber.

Cardiac function requires appropriate proteins in each chamber. Atria requires slow myosin to act as reservoirs, while ventricles demand fast myosin for swift pumping. Myosins are thus under chamber-biased cis-regulation, with myosin gene expression imbalances leading to congenital heart dysfunction. To identify regulatory inputs leading to cardiac chamber-biased expression, we computationally and molecularly dissected the quail Slow Myosin Heavy Chain III (SMyHC III) promoter that drives preferential expression to the atria. We show that SMyHC III gene states are orchestrated by a complex Nuclear Receptor Element (cNRE) of 32 base pairs. Using transgenesis in zebrafish and mice, we demonstrate that preferential atrial expression is achieved by a combinatorial regulatory input composed of atrial activation motifs and ventricular repression motifs. Using comparative genomics, we show that the cNRE might have emerged from an endogenous viral element through infection of an ancestral host germline, revealing an evolutionary pathway to cardiac chamber-specific expression.

Prevalence of low bone mineral density at axial sites and fracture risk in Bulgarian population.

Background: Osteoporosis is a common chronic disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of the bone, which are associated with increased risk of fragility fractures. Currently the most popular tool is the fracture risk assessment model FRAX to calculate the 10-year probability of major osteoporotic fractures (MOF) and hip fractures (HF). Objective: To investigate the prevalence of low BMD at axial sites and fracture risk in Bulgarian population. Methods: We retrospectively analyzed dual energy X-ray absorptiometry (DXA) scan results of 12 478 subjects. Scan results included BMD and T-score assessments of lumbar spine and femoral neck. FRAX major osteoprotic fracture (MOF) and FRAX hip fracture (HF) were assessed in subjects between 40 and 90 years using BMD values. Results: Of total 12478 subjects, 12119 were women and 359 were men. The mean age of the subjects was 61 years (yrs.) ± 10 yrs. The overall prevalence of low BMD at the lumbar spine was 6084/9336 subjects (65.2%). 3502/9336 subjects (37.5%) were considered as osteopenic and 2582/9336 subjects (27.7%) were considered as osteoporotic. The overall prevalence of low BMD at the femoral neck was 2036/3140 (64.8%). 1641/3140 subjects (52.3%) were classified as osteopenic and 395/3 140 subjects (12.6%) were classified as osteoporotic. The mean values of FRAX MOF and FRAX HF increased significantly with increasing the age interval. Conclusion: This study is the largest epidemiological research in Bulgaria up to date about the prevalence of low BMD at axial sites.

Cognitive Impairment and Affective Disorders in Patients With Obstructive Sleep Apnea Syndrome.

Sleep-related breathing disorders could be accompanied by or caused by a variety of medical conditions. They are considered to be a significant medical and social problem. Together with excessive daytime sleepiness, patients with obstructive sleep apnea experience neuropsychological symptoms such as anxiety, attention deficits, cognitive impairment, depressive symptoms and other psychological disturbances leading to social adjustment difficulties. Patients diagnosed with obstructive sleep apnea demonstrate a decline in a wide spectrum of cognitive abilities, including memory, attention, psychomotor speed, executive, verbal and visual-spatial skills. The aim of this study is to investigate the cognitive functioning and affective disorders among patients with obstructive sleep apnea syndrome and to examine the frequency and severity of cases in comparison with a control group consisting of healthy volunteers. Our research has shown that there is a relation between sleep apnea and cognitive impairments and affective changes. This relation can be explained by the direct effect of the syndrome on the patient, where the main connecting factor is the severity and the distribution of excessive daytime sleepiness. Along with treatment of the somatic medical condition, it is extremely important that the patient's mental state is treated as well. Trial Registration: 57/2013, Medical University - Sofia, Bulgaria.