Ethnic differences in right ventricular structure and function in urbanized hypertensive patients in the Gornaya Shoriya region

Objective of this study was to compare right ventricular echocardiography parameters in urbanized hypertensive patients of the Shor and non-indigenous ethnic groups in the Mountain Shoria region. Methods The study included patients with arterial hypertension: 58 Shors and 50 non-indigenous urbanized residents, comparable in age, and divided by ethnicity and gender into 4 groups: Shors men (n = 20), Shors women (n = 38), non-indigenous men (n = 15) and non-indigenous women (n = 35). All underwent echocardiographic examination, and the right heart parameters were studied. Results Shor men with arterial hypertension had the lowest values ​​of the pulmonary artery index, the right atrium dimensions, and the highest values ​​of the blood flow velocity in the right ventricle, et' and st' in comparison with non-indigenous men. Shor women have the lowest values Et and Et/At ratios. RV diastolic dysfunction was detected mainly in women, somewhat more often in Shors. Ethnicity was one of the factors associated with the right ventricular diastolic dysfunction presence. Among the factors associated with the RV diastolic dysfunction were risk factors (smoking, obesity), blood pressure, gender, ethnicity, and left ventricular parameters (diastolic dysfunction and the myocardial mass increase). Conclusion Our study established the influence of ethnic differences on the right heart echocardiographic parameters in Shors and Caucasians with arterial hypertension. The revealed differences should improve the assessment of the right heart structure and function in patients with arterial hypertension from small ethnic groups, which will help to improve the diagnosis and treatment of such patients.

Altered retinal structure and function in Spinocerebellar ataxia type 3

Spinocerebellar ataxia type 3 is an autosomal dominant neurodegenerative disorder caused by expansion of a polyglutamine (polyQ)-encoding CAG repeat in the ATXN3 gene. Because the ATXN3 protein regulates photoreceptor ciliogenesis and phagocytosis, we aimed to explore whether expanded polyQ ATXN3 impacts retinal function and integrity in SCA3 patients and transgenic mice. We evaluated the retinal structure and function in five patients with Spinocerebellar ataxia type 3 and in a transgenic mouse model of this disease (YACMJD84.2, Q84) using, respectively, optical coherence tomography (OCT) and electroretinogram (ERG). We further determined in the transgenic mice: a) the retinal expression pattern of ATXN3 and assessed the distribution of cones and rods by immunofluorescence (IF); and b) the retinal ultrastructure by transmission electron microscopy (TEM). Some patients with Spinocerebellar ataxia type 3 in our cohort revealed: i) reduced central macular thickness indirectly correlated with disease duration; ii) decreased thickness of the macula and the ganglion cell layer, and reduced macula volume inversely correlated with disease severity (SARA score); and iii) electrophysiological dysfunction of cones, rods, and inner retinal cells. Transgenic mice replicated the human OCT and ERG findings with aged homozygous Q84/Q84 mice showing a stronger phenotype accompanied by further thinning of the outer nuclear layer and photoreceptor layer and highly reduced cone and rod activities, thus supporting severe retinal dysfunction in these mice. In addition, Q84 mice showed progressive accumulation of ATXN3-positive aggregates throughout several retinal layers and depletion of cones alongside the disease course. TEM analysis of aged Q84/Q84 mouse retinas supported the IF ATXN3 aggregation findings by revealing the presence of high number of negative electron dense puncta in ganglion cells, inner plexiform and inner nuclear layers, and further showed thinning of the outer plexiform layer, thickening of the retinal pigment epithelium and elongation of apical microvilli. Our results indicate that retinal alterations detected by non-invasive eye examination using OCT and ERG could represent a biological marker of disease progression and severity in patients with Spinocerebellar ataxia type 3.

Understanding the relationship between the microbiome and the structure and function of the pig gastrointestinal tract

The gut epithelium acts as a barrier to the gut environment. The integrity of the epithelial structure and function is thus critical for microbiome-host interaction. The gut microbiome can regulate the utilization and synthesis of mucin, the expressions of the intercellular junction complex, and the functioning of specific epithelial cells, such as enterochromaffin cells and stem cells in pigs. The factors involved include microbial metabolites, especially short-chain fatty acids and host-microbe co-metabolism. Recent studies have revealed the essential role of amino acid metabolism in regulating the gut microbiome and epithelial barrier. This chapter discusses how the pig gut microbiome modulates epithelial structure and function, highlighting findings that reflect the relationship between the gut microbiome, intestinal structure and function.

Circulating miRNAs and Vascular Injury Markers Associate with Cardiovascular Function in Older Patients Reaching End-Stage Kidney Disease

The prevalence of end-stage kidney disease (ESKD) is rapidly increasing and mostly occurring in patients aged 65 years or older. The main cause of death in these patients is cardiovascular disease (CVD). Novel markers of vascular integrity may thus be of clinical value for identifying patients at high risk for CVD. Here we associated the levels of selected circulating angiogenic miRNAs, angiopoietin-2 (Ang-2) and asymmetric dimethylarginine (ADMA) with cardiovascular structure and function (as determined by cardiovascular MRI) in 67 older patients reaching ESKD that were included from ‘The Cognitive decline in Older Patients with End stage renal disease’ (COPE) prospective, multicentered cohort study. We first determined the association between the vascular injury markers and specific heart conditions and observed that ESKD patients with coronary heart disease have significantly higher levels of circulating ADMA and miR-27a. Moreover, circulating levels of miR-27a were higher in patients with atrial fibrillation. In addition, the circulating levels of the vascular injury markers were associated with measures of cardiovascular structure and function obtained from cardiovascular MRI: pulse wave velocity (PWV), ejection fraction (EF) and cardiac index (CI). We found Ang-2 and miR-27a to be strongly correlated to the PWV, while Ang-2 also associated with ejection fraction. Finally, we observed that in contrast to miR-27a, Ang-2 was not associated with a vascular cause of the primary kidney disease, suggesting Ang-2 may be an ESKD-specific marker of vascular injury. Taken together, among older patients with ESKD, aberrant levels of vascular injury markers (miR-27a, Ang-2 and ADMA) associated with impaired cardiovascular function. These markers may serve to identify individuals at higher risk of CVD, as well as give insight into the underlying (vascular) pathophysiology.

Short-term melatonin supplementation decreases oxidative stress but does not affect left ventricular structure and function in myxomatous mitral valve degenerative dogs

Background Cardiac wall stress and high oxidative stress are often found in cases of myxomatous mitral valve degenerative (MMVD) disease and can lead to myocardial injuries and cardiac dysfunction. Melatonin, an antioxidant, has been shown to exert cardioprotection in laboratory animal models. However, its effect on metabolic parameters and left ventricular (LV) adaptation in MMVD dogs has rarely been investigated. This clinical trial hypothesized that a melatonin supplement for 4 weeks would improve metabolic parameters, LV structure (diameters and wall thickness), and LV function in MMVD dogs. Blood profiles, echocardiograms, and oxidative stress levels were obtained from 18 dogs with MMVD stage B2 and C at baseline and after prescribed Melatonin (2 mg/kg) for 4 weeks. Eleven dogs with MMVD stage B2 and C, which received a placebo, were evaluated as a control group. Results In this clinical trial, the baseline plasma malondialdehyde (MDA) was no different between the treatment and placebo groups. The post-treatment plasma MDA levels (4.50 ± 0.63 mg/mL) in the treatment group was significantly decreased after 4 weeks of melatonin supplementation compared to pre-treatment levels (7.51 ± 1.11 mg/mL) (P = 0.038). However, blood profiles and LV structure and function investigated using echocardiography were found not to different between pre-and post-treatment in each group. No adverse effects were observed following melatonin supplementation. Conclusions This clinical trial demonstrated that a melatonin supplement for 4 weeks can attenuate oxidative stress levels in MMVD dogs, especially in MMVD stage C, but does not result in LV structural changes or LV function in MMVD dogs of either stage B2 or stage C.