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Extreme Medicine

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One of the approaches to cartilage tissue restoration problem relies on cellular technologies that use iPSCs, induced pluripotency stem cells that are an unlimited source of cellular material for tissue engineering with significant differentiation potential. However, there are no standardized protocols for chondrogenic differentiation of iPSCs. This study aimed to make cartilage tissue samples using 3D spheroid cultures and following four chondrogenic differentiation protocols, then compare characteristics of the cartilage samples made under different protocols and isolate the most effective way of differentiation. The iPSCs were differentiated chondrogenically, the four protocols were "long", "short", "combined" and with conditioned medium from a primary culture of autologous chondrocytes; the combinations of TGFβ1, BMP2, Chir 99021, and PK factors varied. Microwell plates were used to make spheroids. Immunocytochemical staining, real-time PCR and histological staining enabled assessment of the synthesis and expression profiles. High rates of synthesis and expression of chondrogenic markers Sox9, aggrecan, type II collagen were observed in spheroids experimented with under the "long", "combined" protocols and the conditioned medium protocol. The "combined" differentiation protocol made chondrogenesis most effective, and conditioned medium was highly efficient in inducing and supporting chondrogenic differentiation.
The rapid switch on of the transient short-term responses involved in adjustment of homeostasis plays a key role in human adaptation to low temperatures that is essential for adjustment to low-temperature environment. The network of signaling pathways together with metabolic regulators provide sufficient plasticity of the cells of immune system, the normal function of which is extremely important for successful human adaptation. Sufficient energy supply to immunocompetent cells makes it possible to form an adequate immune response to any negative factor and to ensure adaptive functional rearrangements. The study was aimed to assess the variants of the immunocompetent cell metabolic pathways involved in acquiring individual cold sensitivity. A total of 180 people aged 25–55 (130 females, 50 males) were assessed before and after the short-term whole body cooling. Enzyme immunoassay was used to define the levels of IL10, IL6, TNFα, irisin, transferrin, sTfR, HIF-1α, Sirt3 in peripheral blood and cell lysate. The levels of glycogen (cytochemical methods) and ATP (luciferin-luciferase assay) in lymphocytes were defined. The decrease in peripheral blood lymphocyte levels after cooling was indicative of the formation of immediate adaptive response and activation of glycolysis amid less intense inflammatory response. The increase in the levels of circulating lymphocytes after the cold esposure was associated with activation of inflammatory responses. The lower ratio of HIF-1α/SIRT3 metabolic regulators was found in the surveyed volunteers who showed no changes in the levels of lymphocytes. This indicated predominance of mitochondrial activity in adaptation to low temperatures.
Mortality rate is one of the main indicators of how healthy a population is, and planning and implementing measures aimed at reducing morbidity and increasing life expectancy in the population is impossible without an adequate analysis and interpretation of mortality data. At the same time, as pointed out by many researchers, there are factors external to a human body being that can have a significant effect on the mortality rate in a population. This study aimed to assess the impact of one of these factors, the number of beds in hospitals (per 10,000 people) of cities with population exceeding 100,000 people. The analysis included data from Rosstat (Russian statistics service) on the population size, mortality, number of hospital beds, average monthly wages in 12 cities within the period from 2017 through 2019. Five cities from these 12 were selected as a more homogeneous subgroup in terms of socio-economic conditions. We found a positive correlation between mortality rate per 1000 inhabitants (R > 0.7; p < 0.009) and the number of hospital beds per 10,000 people in the sample of 12 cities. This correlation was higher (R ≥ 0.9; p < 0.037) in the more homogeneous subgroup. A factor that may condition this correlation may be that of deaths of people from other regions in hospitals of the cities in question, which are counted when estimating the mortality rate and have a significant effect on that estimation. The results of the study point to the need to differentiate between people registered in a city and those living there permanently when assessing mortality rate therein.

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It is important to control the levels of specific IgG against SARS-CoV-2 to ensure the timely monitoring of immunity in patients with COVID-19. Yet it is unclear what antibody levels protect against new infection and how long the protection is maintained. The study was aimed to assess the dynamic changes in the levels of IgG against SARS-CoV-2 by the two-year controlled observation. Healthy individuals (n = 70), COVID-19 survivors (n = 42), and people vaccinated with Sputnik V (n = 43) were enrolled. They were followed-up from April 2020 to April 2022. Serum IgG levels were defined (n = 312) using immunochip and the commercially available test system. Significance of differences was estimated using the Mann–Whitney U test for р ≤ 0.05. IgG levels in the disease survivors (median 97.1; 95% CI: 80–162 BAU/mL) and vaccinated individuals (103.1; 78–139 BAU/mL) were significantly higher than in healthy people (4.3; 4.1–4.5 BAU/mL). Intensity of immune response significantly increased after vaccination of the disease survivors (up to 1023; 657–1191 BAU/mL) or administration of booster dose to vaccinated individuals (413; 213–545 BAU/mL). In elderly convalescents (60+), IgG levels were significantly higher, and in vaccinated people these were significantly lower, than in people under the age of 60. IgG levels decreased faster in vaccinated individuals (after 3–4 months), than in the disease survivors, and stabilized at <100 BAU/mL in 60% of subjects within 5–9 months. Thus, intensity and duration of immune response in COVID-19 survivors and vaccinated people vary significantly depending on age, observation period, and additional vaccinations/revaccinations. Three cases of infection after full vaccination were reported over the entire follow-up period, including infection in a patient having a history of the disease and subsequent vaccination.
Earlier, it has been convincingly established that exposure to ionizing radiation (IR) alters the T cell-mediated immunity in the long term. However, a search for papers describing the effect chronic exposure to radiation has on various subpopulations of T-helpers yielded no results. Therefore, we designed this study seeking to investigate the quantitative characteristics of various subpopulations of T-helpers in the peripheral blood of individuals chronically exposed to low-level radiation for a long period of time. The study involved 102 chronically exposed Techa Riverside residents (Russia) aged 60–87 years. The participants were divided into two groups, one comprised of exposed individuals with the average red bone marrow (RBM) irradiation dose of 567 ± 73 mGy, another, the control group, comprised of people with the irradiation dose below 70 mGy. With the help of flow cytometry, we identified the quantitative characteristics of T-helper subpopulations in the peripheral blood at various stages of their differentiation, as well as various T-helper subpopulations of central and effector memory. The study revealed no significant differences in the composition of T-helper subpopulations in the compared groups. We discovered a significant growth of the double positive follicular T-helper 17 subpopulation in the population of central memory T-helpers, which is associated with the increase of RBM (p = 0.04; S = 0.19), thymus and peripheral lymphoid organs (p = 0.03; S = 0.22) irradiation dose. In the group of exposed individuals, the number of naive T-helpers (p = 0.009) and double positive follicular T-helpers 17 in the TEM subpopulation (p = 0.04) was decreasing as the age of participants increased, and the number of effector memory T-helpers, on the contrary, increased with age (p = 0.04). We have not registered similar phenomena in the comparison group.