Search Results (42)

Aim. This study aimed to assess the SARS-CoV-2 herd immunity in the Republic of Armenia (RA) by late 2022. Materials and Methods. A randomized study was conducted from 28 November to 2 December (2022) by the Saint Petersburg Pasteur Institute (Russia) in collaboration with the National Center for Disease Control and Prevention (Armenia). This study was approved by the ethics committees at both organizations. A volunteer cohort (N = 2974) was formed and grouped by participant age, region, or activity. Antibodies (Abs) to viral nucleocapsid antigen (Nc) and receptor-binding domain (RBD) in plasma were determined by ELISA. The statistical significance of differences was calculated using a p < 0.05 threshold, unless noted. Results. At the end of 2022, estimated SARS-CoV-2 seroprevalence (Nc and/or RBD Abs) among the Armenian population was 99% (95%CI: 98.5–99.3). It was evenly distributed throughout the cohort without any significant differences by age, region, or activity. Volunteers with low (32–124 BAU/mL) or medium (125–332 BAU/mL) anti-Nc Ab levels prevailed: 32.4% (95%CI: 30.7–34.1) and 25.5% (95% CI: 24.0–27.1), respectively. Regarding anti-RBD Abs, maximum levels (>450 BAU/mL) were detected in 40% of children. The share of individuals with high anti-RBD Abs levels increased with age, reaching 65% among those aged 70⁺ years. The important contribution to the formation of herd immunity to coronavirus infection was made by vaccination in the preceding period (1 April 2021 to 1 May 2022). The contribution from individuals with post-vaccination immunity was estimated to be above 80%. Hybrid immunity, formed after vaccination of those who had earlier experienced COVID-19, was characterized by greater effectiveness than post-vaccination immunity alone. Conclusions. Within the context of mass prophylactic vaccination, effective herd immunity to SARS-CoV-2 was formed, which helped to stop epidemic spread in the Republic. Full article

Background/Objectives: In the Republic of Serbia, measles vaccination was first introduced in 1971, while combined vaccination (measles, mumps, rubella) was made mandatory in 1996 as part of the national vaccination program. Reported prevalence values for 2023 were <0.75 cases per 100K population for measles, 0.09 cases per 100K for mumps, and no cases of rubella. Methods: This cross-sectional study was performed in May, 2024 as part of the project “Herd Immunity to Vaccine-Preventable and Other Relevant Infections in the Belgradian Population.” It focused on assessing herd immunity to measles, mumps and rubella (MMR) among residents insofar as these remain a public concern despite the availability of vaccines. A total of 2533 subjects were distributed across nine age groups, covering those aged 1–70⁺ years and various professional groups residing in Belgrade. Participants were stratified by age and activity. Upon obtaining individual information by online questionnaire and receiving a signed statement of informed consent, blood samples were obtained for IgG antibody testing (ELISA) to determine MMR serological status. The results were compared to national and international immunization standards to evaluate herd immunity levels. Results: Our results indicate varying levels of immunity for each virus, with specific demographic groups showing different immunity levels. Total measles seroprevalence during this study was 74.7%, with significant variation across all age groups. While high seropositivity was observed in both children (90.7%) and elder age groups (98.4%), middle-aged individuals in the age group 30–49 years showed significantly lower IgG levels. Between 2021 and 2023, there were no registered cases of rubella detected in Serbia, which indicates a high level of immunity. This was confirmed here with consistently high IgG levels across all age groups, with an average seropositivity of 94.8%. Average mumps seropositivity across all age groups was 85.1%. The lowest value was in the young child (1–5 years) age group (76.1%); the highest was in the elderly group (92.6%). Conclusions: The current findings suggest that the Belgradian population has strong overall immunity to MMR, yet with some concerns regarding measles immunity in middle-aged adults, suggesting a potential need for catch-up vaccinations. While rubella status indicates strong herd immunity and minimal risk of outbreaks, mumps immunity in some groups (children, middle-aged adults) is below the protective threshold. While it is still sufficient to prevent widespread transmission, it should be closely observed. To our knowledge, this study is the first of its kind to provide data about MMR seroprevalence in Belgrade. Findings indicate the need for constant surveillance and revaccination of vulnerable/seronegative groups. Full article

Background: Several targeted drugs have been recently approved for the treatment of PIK3CA-mutated hormone receptor-positive (HR+)/HER2-negative (HER2−) breast cancer (BC). This study aimed at a comprehensive evaluation of the spectrum of PIK3CA alterations in Russian BC patients. Methods: The tumor material from 1872 patients with ER+/HER2− BC was tested by a combination of PCR-based methods. Results: Mutations were detected in 693/1872 (37%) cases, including 46 BC with two PIK3CA lesions. The three most common substitutions (E542K, E545K, and H1047R) were identified in 542/693 (78%) PIK3CA-mutated cases, while as many as 5.5–12% of identified mutations were not potentially detectable by common commercial kits. The study included patients of Slavic and non-Slavic ethnicities residing in regions with different climate conditions, however, these factors did not influence the distribution of PIK3CA mutations. The presence of PIK3CA variants was associated with older patient age at diagnosis (p = 0.0002), smaller tumor size (p = 0.005), lower grade (p = 0.005), Ki67 <20% (p = 0.0001) and progesterone receptor-positive status (p = 0.002) at the initial disease diagnosis, and fewer distant metastases at the time of the detection of BC spread (p = 0.0001). In a subgroup of 413 BC patients who received adjuvant tamoxifen or aromatase inhibitors, PIK3CA mutations were not associated with resistance to either type of treatment. Conclusions: The results of this study highlight the need to extend the PIK3CA testing beyond the hotspot regions of this gene. Although PIK3CA alterations contribute to the pathogenesis of HR+/HER2− BC and represent a target for several novel drugs, they are not intrinsically associated with unfavorable clinical characteristics of this subtype of cancer disease. Full article

In this report, we document and analyze a case in which the Irkut virus (IRKV) (Mononegavirales: Rhabdoviridae) caused a fatal human case following a bat bite in June 2021. Unfortunately, the available data did not permit a detailed taxonomic classification of the carrier bat (Chiroptera). The event occurred in the southwestern part of the Sikhote-Alin mountain region (Russian Far East) covered by the Ussuri taiga forest. The symptoms of the illness began with the following: fever; pronounced psychomotor and motor agitation; tremor of the lower jaw and tongue; aphasia; dyslexia; and dysphagia. These rapidly developed, leading to a severe and fatal encephalitis. The patient was not vaccinated for rabies and did not receive rabies immunoglobulin. Using brain sections prepared from the deceased, molecular diagnostics were performed: immunofluorescence (polyclonal anti-rabies immunoglobulin) indicating the presence of the lyssavirus antigen; and RT-PCR indicating traces of viral RNA. Sectional material (brain) was used for whole-genome sequencing, resulting in a near-complete sequence of the lyssavirus genome. The obtained genomic sequence was identified as the Irkut virus. A comparative analysis of the new sequence and other currently available IRKV sequences (NCBI) revealed differences. Specifically, amino acid differences between antigenic sites in the isolate and those of the rabies vaccine strain used regionally were noted. The patient history and subsequent analysis confirm human IRKV infection following bat contact. Like other fatal cases of IRKV infection described earlier, this case occurred in the southern part of the Russian Far East. Two have occurred in the southwestern part of the Sikhote-Alin mountain region. This indicates the possible existence of an active, natural viral focus. Full article

This study presents the first comprehensive examination of ¹³⁷Cs behavior in northern taiga ecosystems of the Kola Peninsula, a previously understudied region regarding radionuclide mobility. The background radioactive contamination of these ecosystems stems from global fallout and differs from more extensively studied contaminated areas. Twelve monitoring sites at varying distances from the Kola nuclear power plant were established to assess ¹³⁷Cs accumulation in dominant plant species across three forest tiers. Gamma-spectrometric measurements revealed high mobility of ¹³⁷Cs with specific activity ranging within 4.7–34.5 Bq/kg in trees, 8.4–164.8 Bq/kg in shrubs, and 15.0–94.5 Bq/kg in mosses. Notably, Ericaceae family plants demonstrated the highest accumulation capacity. ¹³⁷Cs concentrations were significantly higher at the background site (30 km from the power plant) than in the sanitary protection zone, indicating no detectable influence from the nuclear facility. Strong correlations (up to |rs| = 0.93) between bioaccumulation indicators and soil properties were found—particularly with potassium content, exchangeable cation concentration, and organic matter content—suggesting that soil characteristics primarily determine ¹³⁷Cs mobility. These findings highlight the potential risk of ¹³⁷Cs movement through food chains in northern taiga ecosystems, with bioaccumulation coefficients exceeding those of central Russian landscapes and being comparable to those of Scandinavian taiga ecosystems. Full article

Background: Organoids are a valuable model for studying hereditary diseases such as cystic fibrosis (CF). Recombinant adenoviral (rAdV) and adeno-associated viral (rAAV) vectors are promising tools for CF gene therapy and genome editing. Objective: This study aims to determine the most efficient viral vector (rAdV5, rAAV serotypes 5, 6 and 9) and transduction protocol for delivering transgenes to lung organoids (LOs), providing a foundation for future CF gene therapy development. Methods: Three transduction protocols were used taking into account the specificities of LOs’ cultivation in specific matrices, both with and without organoid extraction from the matrix. This work was carried out on organoids from a healthy donor (LOs-WT) and on a patient with cystic fibrosis (LOs-CF). Results: High transduction efficiency was observed with rAdV5 (30% cells), rAAV6 (>80% cells), and rAAV9 (>40% cells). rAdV5 and rAAV9 transduced basal and secretory cells with >90% efficiency. For rAAV9, Protocol 1 (without extraction of organoids from the matrix) showed lower transduction efficiency (33% for LOs-WT, 9% for LOs-CF), significantly lower than that of Protocols 2 (60% for LOs-WT, 59% for LOs-CF) and 3 (46% for LOs-WT, 35% for LOs-CF) with organoid extraction from the matrix (p < 0.005). Conclusions: rAdV5 and rAAV9 are the most promising vectors for the delivery of transgenes to basal and secretory cells in a lung organoid model, providing a solid foundation for CF gene therapy development. Full article

Specific prevention of measles, mumps, and rubella (MMR) is the main prerequisite for a radical reduction in the incidence of these infections in the Kyrgyz Republic (KR). An increase in the number of seronegative individuals observed in recent years has led to an increase in measles incidence. This is directly related to a decrease in collective immunity, which provides protection for the population only in conditions of a high density of immunized individuals and their uniform distribution in the population. The only way to estimate the number of immunized individuals is by conducting serological surveys of collective immunity. Aim of the study: The aim was to study the level of collective immunity to the MMR viruses in the KR. Materials and methods: This study involved a cohort of 6617 residents (volunteers) aged 1 to 70⁺ years, formed in accordance with the Rospotrebnadzor program “Assessment of collective immunity to vaccine-preventable and other relevant infections” and stratified by age and region of residence. During the study, participants filled out a questionnaire and gave venous blood samples to determine IgG antibodies to MMR viruses (ELISA using certified Russian test systems). Results: In December 2023, collective immunity ensured epidemiological well-being only with respect to rubella. The volunteer seropositivity was 94.2% (95% CI: 93.7–94.8). The average measles seropositivity was 78.9% (95% CI: 77.9–79.9). It was significantly lower in children aged 1–17 years and significantly higher than the cohort average in individuals aged ≥18 years. The average mumps seropositivity was 76.4% (95% CI: 75.3–77.4), with the minimum level noted among individuals aged 12–29 years (63.8%; 95% CI: 61.4–66.2). The maximum levels of mumps seropositivity were noted among children aged 6–11 years and older adults who had likely experienced mumps (50–70⁺ years). Seroprevalence distributions by activity correlated with age distributions (all infections). Conclusions: The system of targeted prophylaxis of vaccine-preventable infections adopted in the KR has contributed to the formation of a high level of rubella collective immunity and, to a lesser extent, measles and mumps immunity. The recent trend towards increases in measles and mumps incidence in the KR requires additional efforts to increase collective immunity to these infections. Full article

The severity of MeV infection has been greatly reduced by the development of a live attenuated vaccine, which has been incorporated into vaccination programs in many countries. However, poor access to health facilities, and above all, the increase in anti-vaccination movements, has prevented the achievement of sufficient vaccination coverage. In outbreak scenarios, a rapid and transportable method can improve differential diagnosis, including removing ambiguity in suspected measles cases, contacts, or a cohort. In response to the need, we have developed a new RT-qPCR-based MeV detection assay. The LOD of the developed assay was determined on different PCR machines and the higher threshold was 1–1.2 10³ copies/mL. The joint diagnostic sensitivity of ELISA and RT-PCR (used together) was 100%, and used combinedly, these two methods enable detection of all measles-infected persons, which is extremely important for controlling contagion and spread of infection. During the clinical validation of the assay on 200 clinical samples from measles-suspected cases using ELISA, 157 samples showed a positive result, while 163 positive cases were confirmed by the RT-qPCR assay. The concordance between the two techniques was 93%. According to our results, the real-time RT-PCR approach used in our study is more sensitive and appears to be a more promising method for measles diagnosis during early stages of the disease, likely before the rise of specific IgM antibodies detected by ELISA. Full article

New aromatic co-polyamide-imides (coPAIs) containing both carboxyl and hydroxyl groups in the repeating units were synthesized for the first time. Transport, thermal and morphological properties of dense nonporous membranes from PAIs obtained using the diacid chloride of 2-(4-carboxyphenyl)-1,3-dioxoisoindoline-5-carboxylic acid and diamines 5,5′-methylene-bis (2-aminophenol)) and 3,5-Diaminobenzoic acid, taken in molar ratios of 7:3, 1:1, and 3:7, have been studied. High levels of membrane permeability accompanied by high selectivity for mixtures of liquids with significantly different polarities were determined by realization of intra- and intermolecular interactions in polymer, which was proved by thermal analyses and hydrodynamic characteristics of coPAIs. This effect is discussed in the context of the effectiveness of intermolecular interactions between polymer chains containing carboxyl and hydroxyl functional groups. Full article

Background: Data from birth registries can be studied to assess the prevalence of prenatal alcohol use and associated maternal and neonatal outcomes. Methods: Linked maternal and neonatal data (2015–2018) for alcohol-exposed pregnancies were obtained from the Better Outcomes Registry and Network (BORN) Ontario. Descriptive statistics were generated for maternal demographics, prenatal substance use, mental health/substance use history, and neonatal outcomes. Logistic regression models were performed to assess the odds of prenatal heavy (binge or weekly) alcohol and other substance use based on mental health/substance use history and other maternal demographics, and the impacts of heavy alcohol use and other prenatal substance exposures on neonatal outcomes. Results: A total of 10,172 (2.4%) women reported alcohol use during pregnancy. One-third had pre-existing or current mental health and/or substance use problems, which was associated with significantly higher odds of heavy alcohol use during pregnancy. Prenatal exposure to heavy alcohol use was associated with increased odds of neonatal abstinence syndrome (2.5 times); respiratory distress syndrome (2.3 times); neonatal intensive care unit (NICU) admission (58%); and hyperbilirubinemia (57%). Prenatal exposure to one or more substances in addition to alcohol was associated with significantly higher odds of fetal/maternal/placental pregnancy complications; preterm birth; NICU admission; low APGAR scores; one or more confirmed congenital anomalies at birth; respiratory distress syndrome; and intrauterine growth restriction. Conclusions: It is crucial to routinely screen childbearing-age and pregnant women for alcohol and other substance use as well as mental health problems in order to prevent adverse maternal and neonatal outcomes. Full article

Hemorrhagic fever with renal syndrome (HFRS) and tick-borne encephalitis (TBE) are the most common viral diseases in Russia. HFRS is caused by six different types of hantaviruses: Hantaan, Amur, Seoul, Puumala, Kurkino, and Sochi, which are transmitted to humans through small mammals of the Muridae and Cricetidae families. TBE is caused by viruses belonging to five different phylogenetic subtypes. The similarities in the ecology of HFRS and TBE pathogens is presented here. Hantavirus-infected small mammals can transmit the virus to uninfected animals, and ticks can also transmit hantavirus to other ticks and mammals. Hantavirus transmission from ticks to humans is possible only hypothetically based on indirect data. Over the past 23 years, 164,582 cases of HFRS (4.9 per 10⁵ people) and 71,579 cases of TBE (2.5 per 10⁵ people) were registered in Russia. The mortality rate was 0.4% (668 cases) in HFRS and 1.6% deaths (1136 cases) in TBE. There were 4030 HFRS (2.5%) and 9414 TBE (13%) cases in children under 14 years old. HFRS and TBE cases were registered in 42 out of 85 Russian regions; in 18—only HFRS, in 13—only TBE, and 12 had no reported cases. The prospects of applying a combined vaccine for HFRS and TBE prevention are shown in this paper. Full article

Children and youths diagnosed with FASD may experience a range of adverse health and social outcomes. This cross-sectional study investigated the characteristics and outcomes of children and youths diagnosed with FASD between 2015 and 2018 at the Sunny Hill Centre in British Columbia, Canada and examined the relationships between prenatal substance exposures, FASD diagnostic categories, and adverse health and social outcomes. Patient chart data were obtained for 1187 children and youths diagnosed with FASD and analyzed. The patients (mean age: 9.7 years; range: 2–19) had up to 6 physical and 11 mental health disorders. Prenatal exposure to other substances (in addition to alcohol) significantly increased the severity of FASD diagnosis (OR: 1.18): the odds of FASD with sentinel facial features (SFF) were 41% higher with prenatal cigarette/nicotine/tobacco exposure; 75% higher with exposure to cocaine/crack; and two times higher with exposure to opioids. Maternal mental health issues and poor nutrition also increase the severity of FASD diagnosis (60% and 6%, respectively). Prenatal exposure to other substances in addition to alcohol significantly predicts involvement in the child welfare system (OR: 1.52) and current substance use when adjusted for age (aOR: 1.51). Diagnosis of FASD with SFF is associated with an increased number of physical (R² = 0.071, F (3,1183) = 30.51, p = 0.000) and mental health comorbidities (R² = 0.023, F (3,1185) = 9.51, p = 0.000) as compared to FASD without SFF adjusted for age and the number of prenatal substances. Screening of pregnant women for alcohol and other substance use, mental health status, and nutrition is extremely important. Full article

Radiation dermatitis (RD) is one of the most common side effects of radiation therapy. However, to date, there is a lack of both specific treatments for RD and validated experimental animal models with the use of various sources of ionizing radiation (IR) applied in clinical practice. The aim of this study was to develop and validate a model of acute RD induced using proton radiation in mice. Acute RD (Grade 2–4) was obtained with doses of 30, 40, and 50 Gy, either with or without depilation. The developed model of RD was characterized by typical histological changes in the skin after irradiation. Moreover, the depilation contributed to a skin histology alteration of the irradiated mice. The assessment of animal vital signs indicated that there was no effect of proton irradiation on the well-being or general condition of the animals. This model can be used to develop effective therapeutic agents and study the pathogenesis of radiation-induced skin toxicity, including that caused by proton irradiation. Full article

Background: Progressive myocardial remodeling (MR) in chronic heart failure (CHF) leads to aggravation of systolic dysfunction (SD) and clinical manifestations. Identification of metabolomic markers of these processes may help in the search for new therapeutic approaches aimed at achieving reversibility of MR and improving prognosis in patients with CHF. Methods: To determine the relationship between plasma acylcarnitine (ACs) levels, MR parameters and clinical characteristics, in patients with CHF of ischemic etiology (n = 79) and patients with coronary heart disease CHD (n = 19) targeted analysis of 30 ACs was performed by flow injection analysis mass spectrometry. Results: Significant differences between cohorts were found for the levels of 11 ACs. Significant positive correlations (r > 0.3) between the medium- and long-chain ACs (MCACs and LCACs) and symptoms (CHF NYHA functional class (FC); r = 0.31−0.39; p < 0.05); negative correlation (r = −0.31−0.34; p < 0.05) between C5-OH and FC was revealed. Positive correlations of MCACs and LCACs (r = 0.31−0.48; p < 0.05) with the left atrium size and volume, the right atrium volume, right ventricle, and the inferior vena cava sizes, as well as the pulmonary artery systolic pressure level were shown. A negative correlation between C18:1 and left ventricular ejection fraction (r = −0.31; p < 0.05) was found. However, a decrease in levels compared to referent values of ACs with medium and long chain lengths was 50% of the CHF-CHD cohort. Carnitine deficiency was found in 6% and acylcarnitine deficiency in 3% of all patients with chronic heart disease. Conclusions: ACs may be used in assessing the severity of the clinical manifestations and MR. ACs are an important locus to study in terms of altered metabolic pathways in patients with CHF of ischemic etiology and SD. Further larger prospective trials are warranted and needed to determine the potential benefits to treat patients with CV diseases with aberrate AC levels. Full article

We examined the effects of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline on markers of liver injury, oxidative status, and the extent of inflammatory and apoptotic processes in rats with acetaminophen-induced liver damage. The administration of acetaminophen caused the accumulation of 8-hydroxy-2-deoxyguanosine and 8-isoprostane in the liver and serum, as well as an increase in biochemiluminescence indicators. Oxidative stress resulted in the activation of pro-inflammatory cytokine and NF-κB factor mRNA synthesis and increased levels of immunoglobulin G, along with higher activities of caspase-3, caspase-8, and caspase-9. The administration of acetaminophen also resulted in the development of oxidative stress, leading to a decrease in the level of reduced glutathione and an imbalance in the function of antioxidant enzymes. This study discovered that 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline reduced oxidative stress by its antioxidant activity, hence reducing the level of pro-inflammatory cytokine and NF-κB mRNA, as well as decreasing the concentration of immunoglobulin G. These changes resulted in a reduction in the activity of caspase-8 and caspase-9, which are involved in the activation of ligand-induced and mitochondrial pathways of apoptosis and inhibited the effector caspase-3. In addition, 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline promoted the normalization of antioxidant system function in animals treated with acetaminophen. As a result, the compound being tested alleviated inflammation and apoptosis by decreasing oxidative stress, which led to improved liver marker indices and ameliorated histopathological alterations. Full article