BackgroundLong-living adults often maintain cognitive function despite neuropathological changes, which is often attributed to cognitive resilience (CR)—a combined effect of cognitive and cerebral reserves. CR is influenced by genetic, clinical, sociodemographic, and environmental factors.Materials and methodsWe investigated genetic, clinical, and environmental predictors of CR in 198 dementia-free long-living adults via two neuropsychological examinations over a 2-year period, a geriatric assessment, and a genome-wide association study (GWAS).ResultsLimited mobility, reduced walking, hearing impairment, depression, anemia, lower quality of life, and decreased BMI were key accelerators of CI. Depression, hypercholesterolemia, and lack of hobbies increased the risk of mild cognitive impairment (MCI)-to-dementia progression. GWAS identified CR-associated genetic variants, including a missense mutation in SYNGAP1 (Ile1115Thr) not previously linked to cognitive disorders.ConclusionOur findings corroborated established risk factors for cardiovascular diseases and identified population-specific patterns, with APOE ε4 showing no significant association. Both protein-coding regions and non-coding elements were implicated in CI, suggesting that it is underlain by complex regulatory mechanisms.
Tenuazonic acid (TeA), a mycotoxin produced by Alternaria spp., is a common food contaminant whose potential immunomodulatory effects remain insufficiently characterized. This study investigated changes in circulating cytokine and routine hematological profiles following repeated oral TeA exposure in rats and comparatively reanalyzed a previously reported acute-exposure dataset to explore Orthogonal Implicit Projection (OIP) for multivariate interpretation of correlated biomarker responses. The repeated-dose experiment included 24 male Wistar rats (0, 0.36, and 1.55 mg/kg for 14 days; n = 8 per group), whereas the previously reported acute-exposure dataset comprised 30 rats (vehicle, purified TeA at 30 mg/kg, or an Alternaria alternata extract containing an equivalent TeA dose; n = 10 per group). Repeated TeA administration was associated with marked cytokine alterations, including increased IL-1β at the highest dose and intermediate-dose peaks of TNF-α, IL-2, IL-10, IL-13, and IL-17A, indicating monotonic and non-monotonic response patterns. Acute exposure to purified TeA and the A. alternata extract produced broadly similar cytokine profiles, with increased IFN-γ, IL-1β, IL-6, IL-17A, MCP-1, MIP-1α, and TNF-α, reduced IL-10, and lower IL-10/IL-17A ratios compared with controls. Routine hematological indices showed only modest changes. Exploratory OIP analysis complemented conventional statistical methods by facilitating interpretation of coordinated biomarker responses. Overall, repeated oral TeA exposure was associated with marked cytokine alterations, while comparative reanalysis of the acute-exposure dataset demonstrated a distinct cytokine response under acute exposure conditions. Further studies are needed to clarify the underlying biological mechanisms and their relevance to dietary exposure.
Volatile organic compounds (VOCs) in the vapor phase above an industrial sample of sodium polyacrylate were investigated under various temperature conditions using gas chromatography-mass spectrometry combined with headspace analysis (HS-GC-MS), with the aim of identifying impurities and thermal degradation products. Conditions ensuring effective chromatographic separation of the degradation products mixture with acceptable resolution of major and minor component peaks were proposed. The sodium polyacrylate samples were thermostated at temperatures simulating operational (30 and 60°C) and extreme technological (190°C) conditions, both with and without air purging. The absence of VOCs in the original industrial sample after thermostating at temperatures up to 60°C was established. At 190°C, nine thermal degradation products and impurities were identified for the first time in the vapor phase, including propylene glycol, 1,4-butanediol, nonanal, dimethyl glutarate, alkyl acetals, bicyclic terpenes (cedrene, longifolene), and 2,6-di-tert-butylquinone (antioxidant degradation product). It was demonstrated that short-term purging of the sample with air at 190°C leads to a significant (by an order of magnitude) reduction in the concentrations of all identified VOCs. Based on an analysis of published toxicological data, it was concluded that the identified VOCs pose a low inhalation risk. The obtained results are important for developing safety measures for the high-temperature processing of sodium polyacrylate and confirm its status as a low-hazard material.
Atopic dermatitis is a chronic multifactorial inflammatory skin disease characterized by pruritus, a relapsing course, and characteristic morphological and topographical features that develops in genetically predisposed individuals against the background of a T2-immune response. Cytokines from T helper 2 and type 2 innate lymphoid cells — interleukins 4, 13, and 31 — play a key role in the pathogenesis of the disease, activating the JAK/STAT signaling pathways (primarily JAK1/STAT6). Despite the proven efficacy of selective Janus kinase inhibitors, including the selective Janus kinase inhibitor upadacitinib, in many inflammatory diseases, including atopic dermatitis, there remains a need to accumulate real-world clinical data, especially in patients with refractory atopic dermatitis and comorbid conditions. Aim — to evaluate the long-term efficacy, safety, and dynamics of potential biomarkers during upadacitinib therapy in patients with severe atopic dermatitis and comorbid pathology. This case series presents data from 5 adult patients (3 men, 2 women) with severe atopic dermatitis refractory to standard therapy. All patients received upadacitinib 30 mg once daily for 52 weeks. Efficacy was assessed by dynamics in Scoring Atopic Dermatitis Index, Eczema Area and Severity Index, Investigator’s Global Assessment scores, Numerical Rating Scale; Dermatology Life Quality Index. Safety was evaluated through monitoring of adverse events. Gene expression of cytokines (TARC/CCL17, MDC/CCL22, PARC/CCL18, CTACK/CCL27, eotaxin-3/CCL26, interleukins 4, 13, 17, 22, 25, 33, thymic stromal lymphopoietin) was analyzed using real-time polymerase chain reaction at baseline and at week 16 of therapy. Control over atopic dermatitis symptoms was achieved in all patients: by week 40, 100 % (5/5) of patients had achieved an Eczema Area and Severity Index 90 response, which was maintained until the end of the 52-week observation period. The median Scoring Atopic Dermatitis Index decreased from 65.3 to 2.6 by week 40, and the median Eczema Area and Severity Index score decreased from 47.6 to 0.7 by week 28. Numerical Rating Scale score decreased from 5 to 1 (median) by week 16. During the observation period, 26 mild adverse events were recorded; no serious adverse events were reported. Complete drug-induced remission was observed in one female patient with comorbid alopecia areata. No statistically significant changes were detected in the profile of the studied biomarkers. In this case series, upadacitinib demonstrated high efficacy and a favorable safety profile in patients with severe refractory atopic dermatitis over 52 weeks of therapy. The observed remission of comorbid alopecia areata expands understanding of the drug’s therapeutic potential. Larger prospective studies are needed to confirm these findings and to identify predictive biomarkers.
Relevance . Invasive meningococcal disease (IMD) is one of the most dangerous infectious diseases due to its rapid progression and high risk of fatal outcomes, with infants in their first year of life, starting from the first months, being at greatest risk. Evaluation of the safety and efficacy of co-administration of meningococcal conjugate vaccine MenACWY-TT with pediatric vaccines is necessary for its potential use in the immunization program for infants. Aims . To evaluate the immunogenicity and safety profile of MenACWY-TT vaccine administered according to a 2+1 schedule (vaccination at 3 and 6 months, booster at 12 months), when co-administered with National Immunization Schedule vaccines in healthy children in the Russian Federation. Materials and Methods. An open-label, randomized, multicenter, active-controlled Phase III study was conducted at 8 centers in the Russian Federation. The immunogenicity and safety of MenACWY-TT immunization according to a 2+1 schedule at 3, 6, and 12 months of age co-administered with National Immunization Schedule vaccines, were studied. The study enrolled 225 healthy infants who were randomized in a 2:1 ratio to the MenACWY-TT + routine vaccines group (n = 150) or the comparator group receiving routine vaccines only (n = 75). Immunogenicity against meningococcal serogroups A, C, W, and Y was determined by serum bactericidal assay using human complement (hSBA), and in a subset of vaccinated participants, additionally with rabbit complement (rSBA). Safety was assessed for 30 days after each injection; monitoring for serious adverse events (SAEs) continued until the final visit—30 days after the booster dose at 12 months. Results . At 30 days after the booster dose (12 months), the proportion of participants with seroprotection (hSBA ≥ 1:8) in the MenACWY-TT group was 89.6 % (serogroup A), 82.3 % (C), and 80.2 % (Y and W); in post-hoc analysis excluding one center (at which significantly different values were recorded compared to other sites) – ≥ 93.8 % for all serogroups. After the primary series (at 6 months), serological response was achieved in 70.1–94.8 % of participants. The immunogenicity of routine vaccines when co-administered was comparable to the comparator group. Local reactions to MenACWY-TT (erythema 7.4 %, tenderness 6.0 %) were mild or moderate in severity. Serious adverse events (SAEs) were reported in 2.7 % of participants in both groups, with no established relationship to vaccination. Conclusion . The MenACWY-TT vaccine administered according to a 2+1 schedule from the first months of life demonstrated good immunogenicity and a favorable safety profile when co-administered with pediatric vaccines of the National Immunization Schedule for routine immunization of infants.
