MicroRNA detection in carotid atherosclerosis: prospects for clinical use

Carotid atherosclerosis is a significant cause of cerebrovascular disease. However, with many candidate markers, precise assessment of its development and progression risks is still limited. This paper reviews state-of-the-art concepts of microRNA as an atherogenesis biomarker throughout various stages including endothelial dysfunction, cholesterol/lipid metabolism, inflammation, oxidative stress, angiogenesis regulation, and proliferation and migration of vascular smooth muscle cells. Based on the available literature, we have described most significant microRNAs for each stage characterized in brief. We have visualized interactions between microRNAs and validated target genes with MIENTURNET and suggest and justify a set of microRNAs for further pilot studies of carotid atherosclerosis

Navigated repetitive transcranial magnetic stimulation to correct eating behavior in obesity (clinical cases)

Obesity is a pathological condition caused by overweight and requiring medical intervention. The clinical and scientific experience gained over the past decades has allowed researchers to consider this problem as an independent disease with its own pathophysiological features, prevalence, incidence, approaches to therapy and prevention. One of the most important factors in the pathogenesis of obesity is disordered eating behavior, the central regulation of which is carried out with the active participation of the prefrontal cortex. Impact on this area (for example, using non-invasive brain stimulation) may be one of the promising ways to modulate eating behavior. The article describes clinical cases of treatment of morbid obesity using navigated rhythmic transcranial magnetic stimulation (rTMS). Different patterns of dorsolateral prefrontal cortex (DLPFC) activation before and after rTMS are demonstrated. Possible mechanisms of the influence of DLPFC on the formation of eating behavior are also considered. These data underline the important role of DLPFC dysregulation in obesity, as well as show potentially effective neuromodulation techniques

Red Blood Cell Morphodynamics in Patients with Polycythemia Vera and Stroke

Polycythemia vera (PV) is a Ph-negative myeloproliferative neoplasm (MPN) which is characterized by erythrocytosis and a high incidence of thrombotic complications, including stroke. The study aimed to evaluate red blood cell (RBC) morphodynamic properties in PV patients and their possible association with stroke. We enrolled 48 patients with PV in this cross-sectional study, 13 of which have a history of ischemic stroke. The control group consisted of 90 healthy subjects. RBC deformability and aggregation analysis were performed using a laser-assisted optical rotational red cell analyzer. The following parameters were calculated: aggregation amplitude (Amp), RBC rouleaux formation time constant (Tf), time of formation of three-dimensional aggregates (Ts), aggregation index (AI), rate of complete disaggregation (y-dis), and the maximal elongation of RBC (EImax). Statistical analysis was performed with the R programming language. There were significant differences in RBCs morphodynamics features between patients with PV and the control group. Lower EImax (0.47 (0.44; 0.51) vs. 0.51 (0.47; 0.54), p < 0.001) and γ-dis (100 (100; 140) vs. 140 (106; 188) s−1, p < 0.001) along with higher amplitude (10.1 (8.6; 12.2) vs. 7.7 (6.6; 9.2), p < 0.001) was seen in patients with PV compared with control. A statistically significant difference between PV patients with and without stroke in aggregation amplitude was found (p = 0.03). A logistic regression model for stroke was built based on RBC morphodynamics which performed reasonably well (p = 0.01). RBC alterations may be associated with overt cerebrovascular disease in PV, suggesting a possible link between erythrocyte morphodynamics and increased risk of stroke

miR-33a and Its Association with Lipid Profile in Patients with Carotid Atherosclerosis

Atherosclerosis is a chronic inflammatory disease with a complex, multifactorial pathogenesis, which includes lipid metabolism alterations. miR-33a is a microRNA that plays a key role in cholesterol efflux and promotes atherosclerosis, yet its relationship with lipid markers in carotid atherosclerosis (CA) remains unclear. The objective is to evaluate possible associations between miR-33a expression and lipid biomarkers in patients with CA. This was a prospective study that included 61 patients (median age 66.0 years, 55.7% male) with evidence of CA. Lipid profile (total cholesterol, triglycerides [TG], high-density lipoprotein [HDL] and low-density lipoprotein [LDL] cholesterol) was analyzed. Extraction and quantification of miR-33a-5p/3p was performed according to protocol. Patients were further divided depending on the target LDL level (p p p = 0.02). miR-33a up-regulation is associated with CA and may, in fact, be a key player by targeting cholesterol metabolism. A decrease in LDL cholesterol (<1.8 mmol/L) corresponded to lower levels of miR-33a, yet the direction and causality of this association remains unclear

MicroRNA and Hemostasis Profile of Carotid Atherosclerosis

Carotid atherosclerosis (CA) is an important risk factor for ischemic stroke. We described the miRNA and hemostasis profile of patients with moderate and advanced stages of carotid atherosclerosis and elucidated potential correlations with hemostatic activation. A prospective case-control study included 61 patients with evidence of carotid atherosclerosis (via ultrasound). The study population was divided into groups depending on the degree of carotid artery stenosis: 60% or more (advanced) and p p p = 0.086); miR-29-3p was also higher in the moderate CA group: 10.36 [8.60;14.99] than in advanced CA group: 8.46 [7.47;10.3] (p = 0.001). By-group pairwise correlation analyses revealed at least three clusters with significant positive correlations in the moderate CA group: miR-29-3p with factors V and XII (r = 0.53 and r = 0.37, respectively, p p p < 0.05). Hemostasis parameters did not reveal significant changes in CA patients: the only statistically significant differences concerned factor VIII, plasminogen and (marginally significant) ADAMTS-13 and protein C. Down-regulation of miR-126-5p expression has been identified as a promising biomarker of advanced carotid atherosclerosis with high specificity and sensitivity. Correlation cluster analysis showed potential interplay between miRNAs and hemostatic activation in the setting of carotid atherosclerosis

Dynamics of thermoelastic frictional wear of a coating with piezoelectric interlayer

To study dynamics of a coating wear, this paper deals with an uncoupled thermoelastic contact problem on sliding of a rigid punch over the surface of a thermoelastic coating bonded to an electroelastic interlayer, which itself is bonded to an undeformable substrate. Friction, frictional heating and coating wear on the contact is taken into account. The problem solution was constructed by the Laplace integral transform method and was obtained in the form of the Laplace convolutions. Based on the obtained expressions it is possible to develop technique for monitoring of a coating wear on a sliding contact through values of electric current arising in the piezoelectric interlayer

Dynamics of thermoelastic frictional wear of a coating with piezoelectric interlayer

To study dynamics of a coating wear, this paper deals with an uncoupled thermoelastic contact problem on sliding of a rigid punch over the surface of a thermoelastic coating bonded to an electroelastic interlayer, which itself is bonded to an undeformable substrate. Friction, frictional heating and coating wear on the contact is taken into account. The problem solution was constructed by the Laplace integral transform method and was obtained in the form of the Laplace convolutions. Based on the obtained expressions it is possible to develop technique for monitoring of a coating wear on a sliding contact through values of electric current arising in the piezoelectric interlayer

Genotypes of 2579 patients with phenylketonuria reveal a high rate of BH4 non-responders in Russia.

Phenylalanine hydroxylase (PAH) deficiency is responsible for most cases of phenylketonuria (PKU). Furthermore, numerous studies on BH4-sensitive PAH deficiency have been conducted. To date, BH4, a cofactor of PAH, has not been used to treat PKU in Russia.Genotype data of patients with PKU can be used to predict their sensitivity to BH4 therapy. A cohort of 2579 patients with PKU from Russia was analyzed for 25 common PAH gene mutations using custom allele-specific multiplex ligation-dependent probe amplification-based technology. A mutation detection rate of 84.1% chromosomes was accomplished. Both pathogenic alleles were identified in 73.1% of patients. The most frequent pathogenic variants were p.Arg408Trp (50.9%), p.Arg261Gln (5.3%), p.Pro281Leu (3.5%), IVS12+1G>A (3.1%), IVS10-11G>A (2.6%), and p.Arg158Leu (2.4%). The exact boundaries of a PAH exon 5 deletion were defined as EX5del4154ins268 (c.442-2913_509+1173del4154ins268). Severe phenotypes prevailed in the cohort, and classical PKU was observed in 71.8% cases. Due to the genotype-based prediction, 55.9% of the probands were non-responders to the BH4-treatment, and 20.2% were potential responders. Analysis of genotype data is useful to predict BH4 response in PKU patients. The high rate of non-responders among Russian patients was due to the high allele frequency of severe PAH mutations

Red Blood Cell Morphodynamics in Patients with Polycythemia Vera and Stroke

Polycythemia vera (PV) is a Ph-negative myeloproliferative neoplasm (MPN) which is characterized by erythrocytosis and a high incidence of thrombotic complications, including stroke. The study aimed to evaluate red blood cell (RBC) morphodynamic properties in PV patients and their possible association with stroke. We enrolled 48 patients with PV in this cross-sectional study, 13 of which have a history of ischemic stroke. The control group consisted of 90 healthy subjects. RBC deformability and aggregation analysis were performed using a laser-assisted optical rotational red cell analyzer. The following parameters were calculated: aggregation amplitude (Amp), RBC rouleaux formation time constant (Tf), time of formation of three-dimensional aggregates (Ts), aggregation index (AI), rate of complete disaggregation (y-dis), and the maximal elongation of RBC (EImax). Statistical analysis was performed with the R programming language. There were significant differences in RBCs morphodynamics features between patients with PV and the control group. Lower EImax (0.47 (0.44; 0.51) vs. 0.51 (0.47; 0.54), p −1, p p p = 0.03). A logistic regression model for stroke was built based on RBC morphodynamics which performed reasonably well (p = 0.01). RBC alterations may be associated with overt cerebrovascular disease in PV, suggesting a possible link between erythrocyte morphodynamics and increased risk of stroke

Clinical Characteristics of Cerebrovascular Pathology with Patients Suffering from Ph-Negative Myeloproliferative Disease

Background: Disturbances of microcirculation play a significant role in the development and progression of both acute and chronic cerebrovascular diseases (CVD) and may be associated with different hemogram abnormalities. One of the reasons of the prothrombogenic state of the endothelium is the increase in the number of blood corpuscles leading to (non-Ph) myeloproliferative disorders (MPD) including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PM). Materials and Methods: The study included 167 patients: 102 patients with Ph-MPD and the control group comprising 65 patients with CVD. According to MPD subtype, the patients were divided into three groups: patients with ET (37%, n = 38, male/female 7/31, age 52 ± 7 years), those with PV (40%, n = 41, male/female 20/21, age 50 ± 6 years) and those with PM (23%, n = 23, male/female 5/18, age 54 ± 4 years). Results: In 79% (n = 81) of cases in the study group (with Ph-MPD), patients had chronic CVD, with the most frequently identified symptoms being asthenia (92%) and headache (72%). Headache in Ph-MPD patients was more frequently (86%) associated with PM, while in patients with PV and ET it was equally distributed (70%). Neurological symptoms in 53% of cases were associated with focal changes of the brain on MRI localized in the subcortical area of the frontal and parietal lobes. Twenty-one (21%) patients suffered an acute cerebrovascular accident, 8 of them had thrombotic occlusion of one of the internal carotid arteries leading to hemispheric infarcts. Endothelial function (as measured by flow-dependent dilation of the brachial artery) was severely impaired in all study groups (median 5% with normal cut-off at 10%), the lowest degree of vasodilator activity being specific for patients with a history of stroke (p = 0.011). Conclusion: Patients suffering from MPD had asymptomatic focal changes in the brain in the absence of concomitant vascular disease (hypertension, atherosclerotic vascular disease, heart rhythm disorders) in 50% of cases. MPD, while remaining un- or underdiagnosed, presents a major concern in the cerebrovascular setting. A large number of thrombotic strokes occurring in patients with ET underline the necessity of early diagnostics and preventive therapy in these patients