Diphtheria, tetanus, and pertussis immunity among healthcare professionals and pregnant women in the Moscow region, Russian federation: A preliminary cross-sectional study.

Despite more than 50 years of primary immunization against diphtheria, pertussis, and tetanus in Russia, complicated illnesses, including fatal ones, still occur. The goal of this preliminary cross-sectional study is to see how well pregnant women and healthcare workers are protected against diphtheria, pertussis, and tetanus. The required sample size (pregnant women and healthcare professionals, as well as pregnant women of two age categories) for this preliminary cross-sectional study was calculated using a confidence value of 0.95 and a probability of 0.05. The required number of participants in each group calculated sample size must be at least 59 people. In the Moscow region (Solnechnogorsk city, Russia), a cross-sectional study of pregnant patients and healthcare professionals interacting with children regularly as part of their job from numerous medical organizations was conducted in the year 2021 (n = 655). Antibodies to diphtheria, tetanus, and pertussis toxoids and microorganisms were measured using an enzyme-linked immunosorbent assay (ELISA). The STATISTICA and IBM SPSS Statistics 26.0 were used to process the study results statistically. Descriptive statistics methods, the Mann-Whitney U-test, discriminant analysis with the stepwise selection and analysis of ROC-curves were applied. IgG against diphtheria was found in 99.5% of pregnant women, tetanus in 91.5%, and pertussis in only 36.5%. According to the results of the discriminant analysis, the value of IgG to pertussis is linked to the value of IgA to pertussis and the gestational periods. Immunity to diphtheria was discovered in 99.1% of medical personnel, tetanus in 96.9%, and pertussis in 43.9%, no significant variations with age. When comparing the levels of immunity of pregnant women and healthcare professionals, it was shown that healthcare workers have greater levels of immunity against diphtheria and tetanus. The novel contribution of this study is that it will reveal the proportion of those vulnerable to pertussis, diphtheria, and tetanus among health workers and pregnant women in all age groups under the current national immunization program in Russia. Considering the data obtained from the preliminary cross-sectional study, we believe that it is necessary to conduct a full-scale study on a larger sample and, based on that, make certain changes to the national immunization program in Russia.

Analysis of the Face Mask Use by Public Transport Passengers and Workers during the COVID-19 Pandemic.

(1) Background: The use of face masks and gloves in public places directly shows the commitment of the population to the established regulations. Public transport is one of the most-at-risk places of contamination. The aim of the study was to analyze the face mask use by public transport passengers and workers during the COVID-19 pandemic. (2) Methods: Public transport passengers and workers were surveyed. Periodic intermittent selective observation was used to gauge the level of adherence to the established regulations among public transport passengers. Factor analysis was used to identify factors determining the face-mask-wearing comfort. (3) Results: The majority of passengers (87.5%) and all transport workers (100%) used face masks and gloves. Most of the users wore only face masks. Only 41.6% of passengers and 74.7% of transport workers wore face masks correctly. Motivational attitudes at the implementation of preventive measures were determined: established regulations in the public place (55.8%) and the protection of one's own health and the health of family members (44.2%). Only 22.5% of those wearing face masks believed that doing so will have any effect on the spread of an infectious disease, and 10.8% wore masks to maintain the health of people around themselves. A low level of social responsibility was demonstrated. For 53.4% of workers, face mask wearing was uncomfortable. The majority of workers had adverse reactions to mask wearing: feeling short of breath (52.8%), hyperemia of face skin (33.8%), and facial hyperhidrosis (67.4%). (4) Conclusions: The comfort of wearing a mask is determined by adverse reactions occurrence, the properties of the mask, working conditions, and the duration of wearing the face mask. It is necessary to develop recommendations to reduce wearing discomfort. These recommendations, along with methods of raising the social responsibility of the population, can contribute to a greater commitment of the population to non-specific prevention measures.

STIM2 Mediates Excessive Store-Operated Calcium Entry in Patient-Specific iPSC-Derived Neurons Modeling a Juvenile Form of Huntington's Disease.

Huntington's disease (HD) is a severe autosomal-dominant neurodegenerative disorder caused by a mutation within a gene, encoding huntingtin protein. Here we have used the induced pluripotent stem cell technology to produce patient-specific terminally differentiated GABA-ergic medium spiny neurons modeling a juvenile form of HD (HD76). We have shown that calcium signaling is dramatically disturbed in HD76 neurons, specifically demonstrating higher levels of store-operated and voltage-gated calcium uptakes. However, comparing the HD76 neurons with the previously described low-repeat HD models, we have demonstrated that the severity of calcium signaling alterations does not depend on the length of the polyglutamine tract of the mutant huntingtin. Here we have also observed greater expression of huntingtin and an activator of store-operated calcium channels STIM2 in HD76 neurons. Since shRNA-mediated suppression of STIM2 decreased store-operated calcium uptake, we have speculated that high expression of STIM2 underlies the excessive entry through store-operated calcium channels in HD pathology. Moreover, a previously described potential anti-HD drug EVP4593 has been found to attenuate high levels of both huntingtin and STIM2 that may contribute to its neuroprotective effect. Our results are fully supportive in favor of the crucial role of calcium signaling deregulation in the HD pathogenesis and indicate that the cornerstone of excessive calcium uptake in HD-specific neurons is a calcium sensor and store-operated calcium channels activator STIM2, which should become a molecular target for medical treatment and novel neuroprotective drug development.

Manifestation of Huntington's disease pathology in human induced pluripotent stem cell-derived neurons.

BACKGROUND: Huntington's disease (HD) is an incurable hereditary neurodegenerative disorder, which manifests itself as a loss of GABAergic medium spiny (GABA MS) neurons in the striatum and caused by an expansion of the CAG repeat in exon 1 of the huntingtin gene. There is no cure for HD, existing pharmaceutical can only relieve its symptoms. RESULTS: Here, induced pluripotent stem cells were established from patients with low CAG repeat expansion in the huntingtin gene, and were then efficiently differentiated into GABA MS-like neurons (GMSLNs) under defined culture conditions. The generated HD GMSLNs recapitulated disease pathology in vitro, as evidenced by mutant huntingtin protein aggregation, increased number of lysosomes/autophagosomes, nuclear indentations, and enhanced neuronal death during cell aging. Moreover, store-operated channel (SOC) currents were detected in the differentiated neurons, and enhanced calcium entry was reproducibly demonstrated in all HD GMSLNs genotypes. Additionally, the quinazoline derivative, EVP4593, reduced the number of lysosomes/autophagosomes and SOC currents in HD GMSLNs and exerted neuroprotective effects during cell aging. CONCLUSIONS: Our data is the first to demonstrate the direct link of nuclear morphology and SOC calcium deregulation to mutant huntingtin protein expression in iPSCs-derived neurons with disease-mimetic hallmarks, providing a valuable tool for identification of candidate anti-HD drugs. Our experiments demonstrated that EVP4593 may be a promising anti-HD drug.