HEPATITIS A. THE FEATURES OF DISEASE COURSE IN ADULTS.

OBJECTIVE: The aim: To analyze the incidence of Hepatitis A in Ukraine and Poltava region and to study the clinical and epidemiological features of the course of Hepatitis A in adult patients. PATIENTS AND METHODS: Materials and methods: The course of HA in 96 hospitalized patients was analyzed. The diagnosis of HA was established on the basis of clinical and epide¬miological data and confirmed by the results of laboratory studies (serological and molecular biological). RESULTS: Results: In 2019, in the Poltava region, there was an increase in the incidence of Hepatitis A with a predominance among sick people of working age, among the urban population. This part of people aged from 60 to 75 years old constitutes 9.4%. This study showed that the waterway was the dominant way of HA transmission. The course of the disease in most hospitalized patients was typical and cyclic, with a predominance of a mixed variant of the pre-jaundice period and jaundice. One third of patients survey that they had fever, which persisted with jaundice. CONCLUSION: Conclusions: The findings of this study indicates that the patients older than 40 years were more likely to have concomitant chronic pathology than younger patients, and Hepatitis A was more severe with the development of prolonged cholestasis, wave-like course and recurrence. In most patients under the age of 40, the course of Hepatitis A was mild, but splenomegaly and severe cytolytic syndrome were more common.

TLR4 and TLR7 genetic polymorphism in patients with HIV/HCV-coinfection: prevalence and gender-related features.

OBJECTIVE: Introduction: HIV-infection and chronic hepatitis C is of great concern of current infectology. The paper is aimed at the study of the prevalence of the of TLR4 gene Gly and TLR7 gene Leu polymorphic alleles among patients with HIV/HCV-coinfection in general and with regard to gender, as well as to determine their role in the development of the infection. PATIENTS AND METHODS: Materials and methods: To achieve the objective of the research a cohort and case-control study has been carried out. The total of 535 people has been examined, including: HIV/HCV-coinfected - 104, HIV-monoinfected - 90, patients with chronic hepatitis C - 166 and almost healthy people (population control group) - 175 subjects. RESULTS: Results and conclusion:The study found thatthe prevalence of the TLR4 gene Gly polymorphic allele among patients with HIV/HCV-coinfection, HIV-monoinfection and chronic hepatitis C accounted for 23.1 %, 14.4 % and 14.5 %, respectively, which is significantly higher than the similar index in controls - 3.3 %. The presence of the TLR4 gene Gly polymorphic allele in the genome increases the risk of HIV/HCV-coinfection development, in case of infection, by 9 (OR=8.70, р=0.000), HIV-monoinfection and chronic hepatitis C by 5 times (OR=4.89, р=0,016 and OR=4.9, р=0.011, respectively). TLR7 gene Leu polymorphic allele is recorded with the frequency of 19.9-26.0 % in patients with HIV/HCV-coinfection, HIV-monoinfection and chronic hepatitis C as compared to controls (25.9 %). In female patients with HIV/HCV-coinfection, HIV-monoinfection, chronic hepatitis C and healthy individuals the TLR7 gene Leu polymorphic allele is recorded by 2.1-3.6 times more frequently than in male patients.

Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes.

To capture the full spectrum of genetic risk for autism, we performed a two-stage analysis of rare de novo and inherited coding variants in 42,607 autism cases, including 35,130 new cases recruited online by SPARK. We identified 60 genes with exome-wide significance (P < 2.5 × 10-6), including five new risk genes (NAV3, ITSN1, MARK2, SCAF1 and HNRNPUL2). The association of NAV3 with autism risk is primarily driven by rare inherited loss-of-function (LoF) variants, with an estimated relative risk of 4, consistent with moderate effect. Autistic individuals with LoF variants in the four moderate-risk genes (NAV3, ITSN1, SCAF1 and HNRNPUL2; n = 95) have less cognitive impairment than 129 autistic individuals with LoF variants in highly penetrant genes (CHD8, SCN2A, ADNP, FOXP1 and SHANK3) (59% vs 88%, P = 1.9 × 10-6). Power calculations suggest that much larger numbers of autism cases are needed to identify additional moderate-risk genes.

A minimal actomyosin-based model predicts the dynamics of filopodia on neuronal dendrites.

Dendritic filopodia are actin-filled dynamic subcellular structures that sprout on neuronal dendrites during neurogenesis. The exploratory motion of the filopodia is crucial for synaptogenesis, but the underlying mechanisms are poorly understood. To study filopodial motility, we collected and analyzed image data on filopodia in cultured rat hippocampal neurons. We hypothesized that mechanical feedback among the actin retrograde flow, myosin activity, and substrate adhesion gives rise to various filopodial behaviors. We formulated a minimal one-dimensional partial differential equation model that reproduced the range of observed motility. To validate our model, we systematically manipulated experimental correlates of parameters in the model: substrate adhesion strength, actin polymerization rate, myosin contractility, and the integrity of the putative microtubule-based barrier at the filopodium base. The model predicts the response of the system to each of these experimental perturbations, supporting the hypothesis that our actomyosin-driven mechanism controls dendritic filopodia dynamics.