Rationale - The male reproductive system is an organ sensitive to toxins, and nicotine exposure is recognized as a detrimental factor for male sexual function. Taraxasterol, a bioactive compound with antioxidant and antiapoptotic properties, has potential protective effects against cytotoxicity. This study aimed to evaluate the protective effects of taraxasterol against nicotine toxicity in murine Leydig (TM3) and Sertoli (TM4) cell lines. Methods - Prior to the experiment, TM3/4 cells were treated with taraxasterol extract as a protective agent for 24 h. Cytotoxicity was then induced by exposure to nicotine for 24 h. Finally, cell viability was assessed using the MTT assay, and oxidative stress biomarkers, including malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS), were quantified using commercial kits. The expression of steroidogenic and antioxidant enzyme genes was assessed using quantitative real-time PCR, while apoptosis was measured by assessing the DNA fragmentation rate. All experiments were performed in triplicate, and statistical data processing included analysis of variance (ANOVA) followed by a Tukey's post-hoc test (p<0.05). Results - Although TM3/4 cytotoxicity was not detected up to a concentration of 32 & micro;M, a decrease in viability was detected at a concentration of 64 & micro;M (p<0.001). Nicotine caused a dose-dependent decrease in viability, with IC50 values of 81.67 +/- 5.34 & micro;M and 62.64 +/- 2.55 & micro;M for Leydig and Sertoli cells, respectively. Importantly, taraxasterol improved nicotine-impaired cell viability, accelerated the increase in GSH levels, decreased MDA levels, reduced ROS levels, suppressed apoptosis, and downregulated the expression of steroidogenic and antioxidant genes. Conclusion - Taraxasterol effectively protects Leydig and Sertoli cells from nicotine cytotoxicity by restoring cell viability and apoptotic gene expression, attenuating oxidative stress, and reducing apoptosis through steroidogenesis and antioxidant protection.
This study aimed to determine the role of emotional intimacy and sexual attitude in predicting sexual satisfaction, with the mediating role of hedonism and sensation seeking among childless married women in Kazeroon County. Material and Methods - This study was descriptive and correlational in nature. The statistical population consisted of women visiting family health centers in Kazeroon County in the fall of 2024. A total of 150 participants were recruited using convenience sampling. Data were collected using the following instruments: Sexual Satisfaction Scale by Hudson, Harrison and Crosscup, Sexual Knowledge and Attitude Scale by Besharat, Emotional Intimacy Scale by Walker and Thompson, Sensation-Seeking Scale by Zuckerman, and Snaith- Hamilton Pleasure Scale (SHAPS). Data were analyzed at both descriptive and inferential levels. Results - Emotional intimacy and sexual attitude statistically significantly correlated with hedonism, sensation seeking, and sexual satisfaction in women (P<0.050). The direct effect of emotional intimacy on sexual satisfaction was significant (P<0.050) as well. The direct effect of sexual attitude on hedonism and sensation seeking was also significant (P<0.050). Emotional intimacy had an indirect positive significant effect on sexual satisfaction through the mediating influence of hedonism, with a path coefficient of 0.64 (P<0.050). Sexual attitude had an indirect positive effect on sexual satisfaction in women through hedonism, with a path coefficient of 0.10 (P<0.050). Conclusion - This study identifies emotional intimacy, positive sexual attitudes, and hedonism as key predictors of sexual satisfaction among childless married women, highlighting their significant role in enhancing sexual well-being.
The objective of this study was to comparatively examine the effects of different cognitive load types on the development of mental fatigue, taking into account psychoemotional state and gender differences. Methods - The experiment enrolled 35 volunteers (57% women, 43% men). Mental fatigue was induced using 16 sets of cognitive tasks, each lasting 15 minutes. Two experimental series were employed: the first series involved solving an arithmetic subtraction problem, while the second one involved a short-term memory task. The psychoemotional state of the participants and psychological indicators were assessed before and after completing the cognitive load. Psychoemotional state was assessed using the Well-Being, Activity, Mood (WAM) questionnaire and A.B. Leonov's Acute Mental Fatigue Questionnaire. Cognitive functions were assessed using Anfimov's correction tables and the Kraepelin test. Statistical analysis included the Mann-Whitney test, the Wilcoxon signed-rank test, and Spearman correlation analysis. Results - The results demonstrated that arithmetic subtraction caused a more pronounced decrease in attentional performance (p <= 0.01) and an increase in the number of errors, while working memory load was more dependent on psychoemotional state. Substantial gender differences were identified: women had a chronic fatigue index twice as high as men, a greater increase in acute fatigue after the load, and a more pronounced decline in cognitive performance. Correlation analysis revealed a strong relationship between chronic fatigue, psychoemotional state, and cognitive performance, especially in women. The main results indicate that cognitive load causes significant changes in both the psychoemotional sphere and cognitive performance. Conclusion - Our findings highlight the need for a differentiated approach to preventive measures aimed at minimizing the negative consequences of cognitive load.
Objective - The aim of this study was to examine the dynamics of stress biomarkers and their association with psychological characteristics in healthcare workers during a pilot implementation of a program for reducing occupational burnout. Material and Methods - Physicians and nurses (n=20) from various clinics in Irkutsk, Russia, participated in the pilot program. Stress biomarkers included serum levels of thyroid-stimulating hormone (TSH) and dehydroepiandrosterone sulfate (DHEA-S), and salivary cortisol. Psychological indicators were measured using the Maslach Burnout Inventory (MBI), 12-Item Short Form Health Survey (SF-12), Beck Depression Inventory (BDI), the Ways of Coping Questionnaire (WCQ), Mindful Attention and Awareness Scale (MAAS), and the Five Results - At follow-up, increased salivary cortisol levels were observed only in participants with low baseline burnout, while no significant changes in biomarkers were found in participants with high baseline burnout. In contrast, participants with high baseline burnout levels showed improvements in psychological measures, including reduced burnout symptoms and increased mindfulness. Conclusion - The results indicate heterogeneous psychological and physiological changes depending on baseline burnout levels. Psychological improvements were observed predominantly in participants with high burnout levels, while changes in salivary cortisol levels were observed solely in participants with low burnout levels. Given the pilot nature of the study, the results should be interpreted as preliminary.
Shared decision-making (SDM) is a collaborative approach to healthcare that integrates patient preferences with health care provider expertise to improve the quality of decisions. In family planning, SDM is critical to tailoring contraceptive methods to individual needs. This scoping review, conducted in accordance with the PRISMA-ScR guidelines, examined factors influencing SDM implementation. A literature search in PubMed, ProQuest, Cochrane CENTRAL, and ScienceDirect databases identified ten eligible studies focused on reproductive age and health care providers. Results showed that influencing factors fell into three categories: related to health care providers (communication, empathy, decision aids), patient-related (preferences, lifestyle, insurance), and environmental (stigma, cultural norms, logistical barriers). Effective communication and trust were essential for the successful implementation of SDM, while stigma and systemic constraints were significant barriers, particularly in resource-limited settings. This review identifies multilevel factors influencing the implementation of a SDM model in family planning counseling and integrates them into a holistic framework, thereby providing a novel basis for developing and evaluating interventions to strengthen patient-centered decision-making regarding contraception.
Background - Non-functioning pituitary adenoma (NFPA) is a benign tumor that does not secrete excess hormones but can cause a mass effect. Objective - This study evaluated the clinical characteristics, treatment methods, complications, and outcomes of patients with NFPAs at the Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC) in Basra, Iraq. Methods - A retrospective analysis of 202 patients with NFPAs diagnosed between January 2011 and January 2025 was conducted using the FDEMC electronic database. Radiologically confirmed NFPA with a normal hormonal profile or moderate hyperprolactinemia were the inclusion criteria. Collected data included demographics, clinical picture, radiological findings, treatment methods, and postoperative complications. IBM SPSS Statistics was employed for statistical analysis. Statistical significance was assumed at p<0.05. Results - In the cohort (mean age 44.25 +/- 15.88 years, 59.4% women), macroadenomas predominated (76.2%), with their frequency increasing with age (p<0.001). The most common symptoms were headache (33.2%), adrenal insufficiency (31.7%), hypopituitarism (26.2%), and visual field defects (23.3%). Macroadenomas were more often accompanied by visual field defects (29.9% vs. 2.1%, p<0.001), hypopituitarism (33.1% vs. 4.2%, p<0.001), and adrenal insufficiency (40.3% vs. 4.2%, p<0.001) than microadenomas. Hyperprolactinemia was observed in 44.4% of patients, with no differences depending on adenoma size (p=0.849). Transsphenoidal surgery was performed in 43.6% of cases; conservative treatment was used in 48% of cases. Postoperative complications included secondary empty sella syndrome (ESS) (18.8%), residual tumor (23.8%), and diabetes insipidus (6.4%). Conclusion - Macroadenomas prevailed; transsphenoidal surgery was their primary treatment. The high incidence of obesity and hyperprolactinemia warrants further investigation of their association with NFPA. Prospective studies with longer follow-up periods are needed to optimize treatment and outcomes.
Background - There is no single test that can definitively diagnose hypothalamic-pituitary-adrenal (HPA) insufficiency (HPAI). The goal of our study was to evaluate the effectiveness of measuring serum cortisol, serum dehydroepiandrosterone sulfate (DH EA-S), and plasma corticotropin (ACTH) levels vs. the short cosyntropin stimulation test (standard dose of 250 & micro;g) for the diagnosis of HPAI. Methods - This cross-sectional study was conducted at Faiha Specialized Diabetes, Endocrine, and Metabolism Center (FDEMC) in Basra, Iraq, from November 2021 through October 2022. All patients with suspected HPAI were assessed at baseline for serum cortisol, serum DHEA-S, and plasma ACTH, and then underwent a formal short cosyntropin stimulation test as the gold standard. Results - A total of 169 patients participated in the study. Of these, 134 (79.3%) were women. Although the overall age of the cohort ranged from 20 to 80 years (mean +/- standard error: 38.8 +/- 0.94 years), the majority (77.5%) represented the 21-50-year age range. The cutoff value of serum cortisol predicting an abnormal short cosyntropin test result was <5.31 & micro;g/dL, with a maximum sensitivity and specificity of 87.7% and 90.4%, respectively. The serum DHEA-S level of <31.11 & micro;g/dL predicted an abnormal short cosyntropin test result, with a sensitivity of 89.2% and a specificity of 62.7%. The least reliable parameter was the plasma ACTH level, with a cutoff value of <5.30 pg/mL, with the lowest sensitivity and specificity (68.8% and 74.5%, respectively). Conclusion - For excluding HPAI, the serum cortisol level at 9-11 a.m. has the best prognostic value, while DHEA-S has an intermediate value, and plasma ACTH is the least reliable test. The combination of serum cortisol and serum DHEA-S levels provides the best results for diagnosing HPAI.
Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure (HF). Considering the rapidly progressive course of this difficult-to-treat disease and the frequency of decompensation (especially among young patients), DCM poses a significant challenge to the healthcare system. We present a clinical case of successful combination treatment using repeat cell therapy in a young patient with Class IV DCM. The patient was hospitalized with a clinical picture of chronic HF (CHF) with a left ventricular ejection fraction (LVEF) of 20% and elevated N-terminal prohormone of brain natriuretic peptide (NT-prBNP) levels of 25,000 pg/mL. He was followed for two years with optimal medical therapy for CHF. He underwent four courses of autologous cell therapy at four-month intervals. During follow-up, the patient’s clinical condition significantly improved, dyspnea and edema resolved, while physical activity tolerance increased. LVEF has increased to 53%, rGO-BNP marker of HF has normalized, and quality of life has improved based on the Minnesota Multiphasic Personality Inventory (60 pts.).
In this article, we discuss the feasibility of combination antiarrhythmic drug therapy in the form of a polypill. In our opinion, this type of treatment is currently limited by various factors discussed in this article. Large-sample studies are needed to evaluate the efficacy and safety of different antiarrhythmic drug combinations in patients with atrial fibrillation, as well as supraventricular and ventricular arrhythmias.
Introduction - Overweight and obesity are recognized as significant risk factors for adverse outcomes after coronary artery bypass grafting (CABG). One of the key mechanisms linking obesity to the progression of cardiovascular pathology is endothelial dysfunction, marked by reduced nitric oxide (NO) bioavailability. Objective - To evaluate the association between epicardial fat thickness (EFT), NO levels, and echocardiographic parameters in overweight patients during cardiac rehabilitation after CABG. Methods - We enrolled 155 post-CABG patients stratified by body mass index (BMI). Clinical and demographic characteristics, plasma NO levels, and echocardiographic parameters were assessed. Regression analysis was used to identify predictors. Results - Overweight patients exhibited a statistically significant increase in EFT and a decrease in plasma NO levels compared to normalweight patients (p<0.05). EFT correlated positively with left ventricular myocardial mass and diastolic dysfunction. Regression analysis identified BMI as an independent predictor of adverse changes (odds ratio [OR]=1.917; 95% confidence interval [CI]: 1.204-3.052; p=0.006). BMI remained an independent predictor of these changes and demonstrated diagnostic utility in predicting the risk of endothelial dysfunction, as indicated by NO levels. Conclusion - In post-CABG patients, overweight is associated with increased EFT, reduced NO levels, and impaired diastolic function of the myocardium. These findings underscore obesity's role as a significant predictor of endothelial dysfunction and adverse cardiac remodeling postoperatively.
Background — Prenatal alcohol exposure (PAE) causes fetal alcohol spectrum disorder (FASD). The hippocampus, an important part of the limbic system, is pathologically affected in FASD. The goal of this systematic review and meta-analysis was to evaluate biomarkers of neuroinflammation and neurogenesis in the hippocampus in FASD. Methods — All studies reporting the effects of PAE on the hippocampus were collected (as of June 12, 2025) in valid WoS, PubMed, Scopus, and ScienceDirect databases using MeSH keywords. After primary and secondary screening (PRISMA 2020 guidelines), the selected articles underwent study quality assessment (ARRIVE checklist). Data were extracted in two main areas: neuroinflammation (IL-1β, IL-6, and TNF-α cytokines) and neurogenesis (Ki67, DCX, and BrdU markers). Random and fixed effects models (comprehensive meta-analysis software: CMA version 2) were used for statistical analysis. Subgrouping and the I2 index were used to assess heterogeneity. Publication bias and sensitivity were also assessed. P-value of 0.05 or less was considered statistically significant, and a 95% confidence interval (95% CI) was calculated. Results — Of the 231 articles, 8 high-quality experiments were used for data extraction. The total effect of FASD on hippocampal neuroinflammation and neurogenesis was 1.323±0.125 (95% CI=1.078–1.568, p=0.000) and 0.288±0.482 (95% CI=-0.655–1.232, p=0.549), respectively. The results of subgroup analysis were as follows: IL-1β (0.972±0.222, 95% CI=0.537~1.407, p=0.000), IL-6 (1.954±0.204, 95% CI=1.555~2.354, p=0.000), TNF-α (0.916±0.224, 95% CI=0.476~1.356, p=0.000), BrdU+ cells (-1.468±1.109, 95% CI=-3.641~0.705, p=0.185), DCX+ cells (-0.234±1.191, 95% CI=-2.569~2.101, p=0.844), and Ki67+ cells (0.932±0.598, 95% CI=-0.241~2.104, p=0.119. Conclusion — FASD may lead to hippocampal neuroinflammation in neonates.
Objective - To compare the longitudinal dynamics of clinical parameters in patients with arterial hypertension (AH) according to the presence of obstructive airway disease (OAD)-encompassing asthma, chronic obstructive pulmonary disease (COPD), and pre-COPD-during the year following COVID-19-related lung damage. Methods - 127 patients with AH were examined during hospitalization for COVID-19-related lung damage and re-examined at 3 and 12 months after discharge. The OAD group included 38 patients, while the non-OAD group included 89 patients; the groups were matched for age, gender, BMI, severity of AH, and comorbidities. Results - Non-OAD patients had a higher incidence of stage 3 hypertension. One year after discharge, left-ventricular (LV) relaxation disorders were more frequently detected in the non-OAD group. Right-heart structural and functional parameters also worsened: the right atrial volume index increased (15.0 [12.0; 17.8] mm/m2 vs. 16.7 [14.2; 19.5] mm/m2, p=0.004); basal right-ventricular width rose (32.2 +/- 4.7 mm vs. 33.5 +/- 4.7 mm, p=0.007); tricuspid annulus displacement amplitude fell (23.4 +/- 2.7 mm vs. 22.4 +/- 2.2 mm, p=0.009); and its early diastolic velocity decreased (13.0 [11.0; 15.0] cm/s vs. 12.0 [11.0; 14.0] cm/s, p=0.047). Conclusion - In AH patients, the hospital course of COVID-19-related lung damage did not differ between those with and without OAD. One year after discharge, OAD patients showed a significantly reduced frequency of heart failure with preserved ejection fraction (HFpEF) incidence compared to three months after COVID-19. In non-OAD patients, BMI and the prevalence of stage 3 arterial hypertension increased, LV relaxation disorders were more frequent, and right-heart structural and functional parameters were worse compared with OAD patients.
This first-in-human Phase I study assessed the safety and tolerability of the industrial-grade batch of AV-22 dry medicinal extract (Gratiola officinalis L.) (Developing organization: Saratov State Medical University named after V.I. Razumovsky, Ministry of Health of Russia). Objective - To evaluate the safety, tolerability, and maximum tolerated dose (MTD) of a single oral dose of AV-22 in patients with advanced genitourinary cancers. Material and Methods - An open-label, single-center, dose-escalation study was conducted using the classic 3+3 design [12]. Twenty patients with advanced genitourinary cancers were sequentially enrolled in five dose cohorts (125, 250, 375, 500, and 625 mg). Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Tumor response was assessed at day 28 using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Pharmacokinetic analyses quantified plasma concentrations of verbascoside, cucurbitacin D, cucurbitacin E, and cucurbitacin I after oral administration. Concentrations were quantified using a validated method of high-performance liquid chromatography with a mass-selective detector (HPLC-MS/MS) with a linear range of 1-1000 ng/mL (lower limit of quantification (LLOQ): 1 ng/mL). Serial blood samples for pharmacokinetic analysis were collected before and after drug administration at designated time points: 0.5, 1, 3, 6, 9, 12, 15, 18, 24, and 36 hours, as well as on days 7, 14, and 28 (all samples obtained in the morning after an overnight fast). Results - All 20 patients completed the observation protocol (mean age =65.8 +/- 9.6 years). No dose-limiting toxicity (DLT) or serious adverse events were reported, and the maximum tolerated dose (MTD) was not reached at any dose level up to 625 mg. Plasma concentrations of all analyzed active components (verbascoside, cucurbitacins D, E, and I) were below the lower limit of quantification (LLOQ=1 ng/mL) at all sampling time points, precluding the calculation of standard pharmacokinetic parameters (e.g., AUC, Cmax, Tmax, t1/2). Statistically significant changes in individual laboratory parameters (e.g., hemoglobin, thrombin time, and total bilirubin) were small in magnitude and were not accompanied by clinically significant deviations. Follow-up computed tomography or magnetic resonance imaging (CT/MRI) was performed in all patients on day 28: all 20 patients (100%) achieved stable disease, with no partial or complete responses or progressive disease. Conclusion - A single 125-625 mg dose of AV-22 exhibited a favorable safety profile and tolerability in patients with advanced genitourinary cancers. The data obtained justify further studies with multiple doses and extended biomarker monitoring.
Background - Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by polycystic ovaries and associated oxidative stress. This study assessed the potential beneficial effects of ozone therapy on ovarian tissue in mice with induced PCOS. Methods - Forty-two female mice were distributed between six groups: a control group, a PCOS group, a PCOS group treated with ozone (45, 60, and 70 mu g/mL), and a PCOS group treated with clomiphene citrate (1.5 mg/kg). PCOS was induced by injection of estradiol valerate (EV), and treatment was administered for four weeks. Data were analyzed using SPSS software, with a significance level of p<0.05. Results - Histological analysis showed that PCOS significantly disrupted the ovarian structure, decreasing the number of primary (7.80 +/- 0.45 vs. 13.00 +/- 0.71; p<0.05) and preantral follicles (3.00 +/- 1.58 vs. 9.80 +/- 0.84; p<0.05), while increasing the number of antral follicles (12.20 +/- 0.45 vs. 6.20 +/- 0.45; p<0.05) and follicular cysts (7.60 +/- 0.55 vs. 0; p<0.05). Ozone at a dose of 45 mu g/ml significantly restored the number of follicles and improved the corpus luteum count, as well as the thickness of the follicular membrane and granulosa cell layer (p<0.05) compared with other doses. Biochemically, PCOS increased the levels of MDA (25.82 +/- 4.61 vs. 3.04 +/- 0.45 nM/ml; p<0.05) and LH (16.72 +/- 1.54 vs. 8.52 +/- 1.87 mIU/ml; p<0.05), and decreased the level of FSH (1.80 +/- 0.01 vs. 6.86 +/- 0.32 mIU/ml; p<0.05). Ozone at a concentration of 45 mu g/ml significantly normalized these levels (p<0.05), while all doses of ozone and clomiphene citrate reduced the elevated level of DHEA. Gene expression analysis revealed PCOS-induced increase in IGF (similar to 22-fold), Cox2 (similar to 28-fold), and NF-kappa B (similar to 3.5-fold), as well as a similar to 0.2-fold decrease in Nrf2 (p<0.05). Ozone at a dose of 45 mu g/mL effectively reversed these pathological changes (p<0.05) compared with other doses (60 and 70 mu g/mL) in a PCOS mouse model. Conclusion - Ozone therapy at a dose of 45 mu g/mL (compared with other doses in this study) reduced histopathological damage, biochemical imbalances, and inflammatory gene expression in PCOS.
Background - The COVID-19 pandemic and subsequent changes in health policies may have impacted the mental health of medical students in China. Objective - This study aimed to assess the mental health status of Chinese medical students after adjustments to the country's pandemic response measures. Methods - We conducted a cross-sectional online survey of 872 medical students using several standardized instruments: 7-item Generalized Anxiety Disorder (GAD-7), 9-item Patient Health Questionnaire (PHQ-9), 10-item Connor-Davidson Resilience Scale (CD-RISC10), the Impact of Events Scale-Revised (IES-R), and the Simplified Coping Styles Questionnaire (SCSQ). Results - The survey revealed that 25.0% of participants had anxiety symptoms, 35.7% had symptoms of depression, and 22.13% had post-traumatic stress disorder (PTSD). Significant influencing factors included education level, history of close contact with COVID-19 patients, personal history of infection, and physical health status (p<0.05). Multivariate logistic regression revealed that individuals with a history of COVID-19 were more likely to report mild anxiety; higher education was associated with moderate to severe anxiety, as well as mild, moderate, and severe depression; individuals with chronic medical conditions were more likely to report anxiety, depression, and Conclusion - Following policy adjustments in the context of the pandemic, medical students experienced significant mental health problems, such as anxiety, depression, and PTSD. Support efforts should involve upper-year students and students with chronic diseases, and should focus on strengthening resilience and positive coping skills.
Background — C-reactive protein (CRP) and cancer antigen 15-3 (CA 15-3) are commonly studied biomarkers in breast cancer, but their prognostic significance at diagnosis remains unclear. Aim: Our study aimed to assess the prognostic value of serum CRP and CA 15-3 levels in newly diagnosed breast cancer patients. Methods — We enrolled 39 patients with primary breast cancer in our single-center study. Serum CRP and CA 15-3 levels were measured at diagnosis. Receiver operating characteristic (ROC) analysis was employed to determine optimal cut-off values. Survival outcomes were analyzed. Results — Elevated CRP and CA 15-3 levels were associated with shorter progression-free survival and overall survival. In particular, CRP demonstrated significant prognostic value. However, due to the critically small sample size, the obtained results should be considered preliminary. Conclusion — Serum CRP and CA 15-3 levels may serve as potential prognostic markers in breast cancer. These results are hypothetical and require confirmation in larger cohorts.
Background - Fibroepithelial tumors of the mammary gland known as fibroadenoma (FA), being one of the most common variants, represent a rather heterogeneous group of diseases, the pathogenetic mechanisms of which remain largely unknown. This study aimed at analyzing two categories of putative changes in the cell-mediated immunity in women diagnosed with FA: (a) changes affecting the transcriptomic profile of the peripheral blood mononuclear cell (PBMC) fraction and the spectrum of activated/ dysregulated signaling pathways that form a specific immune and stromal environment of the tumor; and (b) changes in (co-)expression of immune checkpoint markers - CD279/PD-1, CD274/PD-L1, CD366/TIM3 and CD223/LAG3-in the CD4 and CD8 subsets of circulating T lymphocytes. Methods - Transcriptome profiling was performed using high-throughput RNA sequencing on the Illumina next-generation sequencing platform, followed by bioinformatic analysis of the resulting datasets including differential gene expression and signaling pathway enrichment analysis. Immune checkpoint marker expression patterns were identified using multicolor flow cytometry. Results - Principal component analysis and hierarchical clustering of the transcriptome datasets revealed three clusters, with the FA cluster clearly distinguishable from the control group. DESeq2 software package detected a total of 334 genes with differential expression between PBMCs from FA patients and healthy controls (with an adjusted p-value <0.05 and fold change of expression (FC)>2.0). Gene Ontology (GO) and KEGG enrichment analyses revealed that differentially expressed genes (DEGs) were enriched in over 500 GO terms of the Biological Processes sub-ontology with a false discovery rate (FDR) set to <0.01 and more than 20 KEGG signaling pathways (FDR<0.25). The most frequently occurring GO terms included Th1 activation processes, monocyte maturation, and inflammatory responses mediated by interferon-gamma (IFN-gamma) and IL-12 signaling pathways, as well as IL-1, IL-6, IL-8, and TNF alpha-dependent pathways. Genes enriched in the negative regulation of mononuclear cell migration and T cell differentiation (via IL-4-and IL-10-dependent mechanisms) were downregulated. Another group of overrepresented terms was related to the cellular response to stress including the antioxidant defense responses mediated by metallothionein MT1E and SOD1. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the involvement of various functional activities of antigen-presenting cells (macrophages, dendritic cells). Gene set enrichment analysis (GSEA) was performed using molecular signatures obtained from the MSigDB database (viz., the C4 and C7 ImmuneSigDB, and Hallmark subcollections) revealed that transcriptomic changes detected in the FA datasets were linked to specific metaprograms and gene networks associated with cancer, such as epithelial-mesenchymal transition (EMT) or myofibroblast-specific metaprogram (FDR<0.05; normalized enrichment score: |NES|>1.5). GSEA also demonstrated the involvement of pathways responsible for the differentiation and functional activity of regulatory T cells (Treg) (FDR<0.05, |NES|>1.8) and altered PD1 expression status (PD1(low)/PD1(high)), indicating immune exhaustion. Flow cytometry analysis demonstrated an increase (p<0.05, U test) in the percentage of CD4/CD8 T cells co-expressing three checkpoint markers (PD1(+)PD-L1(+)TIM3(+)or PD1(+)PD-L1(+)LAG3(+) cells) in PBMCs from FA patients vs. the control group, suggesting enhanced immune checkpoint signaling and expansion of exhausted T cells. Conclusion - To our knowledge, this is the first study to examine the transcriptomic features of circulating lymphocytes and monocytes in women diagnosed with breast FA and the first to analyze the co-expression pattern of immune checkpoint markers. Our results demonstrate the involvement of specific immune system molecular pathways in the pathogenesis of FA and the intensification of immune exhaustion mechanisms.
Objectives - To determine whether vertical take-off and landing (VTOL) drone transport affects parameters of a global hemostasis assay and to identify UAV transport conditions that preserve sample integrity. Methods - Platelet-free plasma was prepared from whole-blood samples collected from 30 healthy volunteers (11 men, 19 women; ages 22-38 years) according to pre-analytical standard operating procedures. Thrombodynamics (Hemacore T-2, Russia) was employed to assess lag time (Tlag), initial and stationary clot-growth velocities (Vi, Vst), clot size (CS), clot density (D), and spontaneous clotting time (Tsp). Samples were evaluated under three conditions: (i) immediately after collection; (ii) after laboratory storage (reference); and (iii) after transport by the InnoVtol-3s VTOL UAV over distances up to 250 km. Results - No statistically significant differences were observed among the Immediate, Reference, and UAV-transported groups for Vi, Vst, Tlag, CS, or D (Kruskal-Wallis test with Dunn-Holm; padj >= 0.05 for all pairwise contrasts.) Spontaneous clotting time (Tsp) was absent in all samples within the observation window. Across all groups, values remained within analytical variation (<4%), indicating assay stability under the tested transport conditions. This study is the first to demonstrate that transporting plasma samples via a VTOL UAV (InnoVtol-3s) does not significantly affect the analytical outcomes of global coagulation testing using the Thrombodynamics assay. Conclusions - Under the examined conditions, VTOL UAV transport preserved the analytical integrity of Thrombodynamics in plasma from healthy donors. These findings are preliminary and warrant further investigation.
Background — Tuberculosis (TB) is a priority health problem on the global health agenda. TB programs face challenges with delays in diagnosis and treatment. Perceived stigma can prevent people from seeking testing, accessing health services and treatment. Objective — To review and document the existing evidence on the impact of stigma on TB prevention and control efforts. Methods — The study used a scoping review method, which follows PRISMA as a guideline. Articles were identified in the Scopus database. The search was conducted on September 1, 2024. The study also employed bibliometric analysis using VOSviewer software version 1.6.20. Results — A total of 31 articles on stigma in TB patients published in 2020-2024 were reviewed: 18 articles (58.06%) were related to access to health services, 8 articles (25.81%) dealt with medication adherence, and 5 articles (16.13%) were about provisioning TB preventive therapy. Studies on stigma in TB cases still dominate in cases involving adults, effect of gender issue, TB-HIV links, and are related to health awareness, attitudes and behavior. Conclusion — This study provides evidence on the impact of persistent community stigma, which is a barrier to TB elimination efforts. Stigma discourages TB patients from seeking health care, affects their medication adherence and provision of TB preventive therapy.
An analysis of large-scale studies utilizing actigraphy and wearable devices for continuous monitoring of physiological measures was conducted. Data had been obtained from the UK Biobank and the National Health and Nutrition Examination Survey (NHANES) for use in the studies. The link between circadian rhythm deviations and health status was investigated. The amplitude and phase of circadian rhythms, along with variability parameters of physical activity, skin temperature, and light exposure, were found to be informative markers of key health indicators, including morbidity, mortality, and life expectancy. These findings highlight the critical role of circadian markers – amplitude, phase, and variability – in predicting health risks related to metabolic and sleep disorders, emotional well-being, and cognitive function. By exploring nonlinear associations between chronotype and health risks, we propose that personalized adjustment of sleep-wake phase, based on light hygiene and physical activity regimes and taking into account age, sex, and genetic cofactors, may contribute to the advancement of health-preserving technologies and the extension of human lifespan.
