INTRODUCTION: Physical inactivity is a well-established risk factor for ischemic stroke, yet the global burden of ischemic stroke attributable to physical inactivity among older adults remains poorly understood. This stu...INTRODUCTION: Physical inactivity is a well-established risk factor for ischemic stroke, yet the global burden of ischemic stroke attributable to physical inactivity among older adults remains poorly understood. This study aimed to investigate the global burden of ischemic stroke attributable to physical inactivity among adults aged 55 and above from 1990 to 2021, focusing on socioeconomic status, regional variations, and temporal trends. MATERIAL AND METHODS: We calculated death and disability-adjusted life years (DALYs) on a global scale and across various Socio-demographic Index (SDI) regions. To analyze temporal trends, we employed joinpoint regression analysis. The total changes in disease burden were partitioned into three fundamental drivers: aging demographics, population expansion, and epidemiological trends. Additionally, the Bayesian age-period-cohort model was applied to forecast future trends. RESULTS: The global age-standardized death rate (ASDR) declined from 12.9 (95% UI: -2.3 to 28.6) in 1990 to 8.8 (95% UI: -2.7 to 21.2) in 2021, with an estimated annual percentage change (EAPC) of -1.53 (95% CI: -1.68 to -1.38). High SDI regions experienced the sharpest declines in both deaths and ASDR, while low and low-middle SDI regions showed slower progress. Joinpoint regression analysis revealed distinct temporal trends, with high SDI regions exhibiting the most substantial declines. Decomposition analysis highlighted the contributions of population growth and aging to increased disease burden, while epidemiological changes played a beneficial role in reducing the burden. Age and sex patterns revealed progressive increases in death and DALY rates with age, along with gender disparities, particularly in older age groups. The Bayesian age-period-cohort (BAPC) model projected a U-shaped trend in global ASDR for males and a consistent decline for females by 2050. CONCLUSIONS: This research offers a thorough evaluation of the global impact of ischemic stroke due to physical inactivity in older adults between 1990 and 2021. The results underscore substantial inequalities in socioeconomic status and regional progress, noting particularly slow advancements in low and middle-income countries. The study highlights the necessity for focused interventions, enhanced healthcare accessibility, and robust stroke prevention initiatives to mitigate the global impact of ischemic stroke linked to physical inactivity. Future investigations should concentrate on examining the socio-economic, cultural, and policy-driven factors shaping these trends, thereby informing evidence-based approaches to alleviate the burden of ischemic stroke.
INTRODUCTION: To evaluate global trends and SDI-related inequalities in the burden of ischemic heart disease (IHD) from 1990 to 2021, and project trajectories to 2035. This analysis provides crucial evidence to inform he...INTRODUCTION: To evaluate global trends and SDI-related inequalities in the burden of ischemic heart disease (IHD) from 1990 to 2021, and project trajectories to 2035. This analysis provides crucial evidence to inform health policy and resource allocation for reducing future disparities. MATERIAL AND METHODS: Using Global Burden of Disease (GBD) 2021 data, we analyzed IHD prevalence, incidence, deaths, and disability-adjusted life years (DALYs) across 204 countries. Analyses included temporal trends, decomposition, inequality assessment, and Bayesian projections. RESULTS: From 1990 to 2021, global age-standardized death rates declined annually by 1.3% and DALYs by 1.2%, while prevalence showed a slight increase (AAPC = 0.03%). High-SDI regions achieved the largest reductions, whereas low- and middle-SDI regions experienced persistent or rising burdens. Decomposition analysis indicated that population growth (110%) and aging (67%) were the main drivers of increasing DALYs, partially offset by epidemiological improvements (-77%). By 2035, despite continued declines in age-standardized rates, the absolute number of IHD cases is projected to increase by 18.2%. CONCLUSIONS: IHD remains a major global health challenge, with substantial SDI-driven disparities that persist despite overall progress. Strengthening prevention in low- and middle-SDI regions, addressing the growing healthcare demands of aging populations, and fostering sustained international collaboration are critical to reducing inequalities, guiding resource allocation, and ultimately alleviating the global burden.
In patients with hypertension, intestinal dysbiosis and increased intestine permeability are commonly observed. Modifications of intestinal microbiota with certain probiotics, prebiotics, and synbiotics, as well as gut m...In patients with hypertension, intestinal dysbiosis and increased intestine permeability are commonly observed. Modifications of intestinal microbiota with certain probiotics, prebiotics, and synbiotics, as well as gut microbiota transfer, have been associated with a reduction in blood pressure. Therefore, these interventions, especially probiotics, can be employed as adjuncts to hypertension therapy. Bacteria constituting dysbiotic intestinal microbiota produce compounds with hypertensinogenic activity (trimethylamine - TMA, pathogen-associated molecular patterns - PAMPs). In addition, in a state of dysbiosis, a decrease in the production of compounds with antihypertensive activity (short-chain fatty acids - SCFAs) is observed. A diet high in salt significantly alters the intestinal microbiota, and such dysbiosis has been implicated in the pathogenesis of salt-sensitive hypertension. This narrative review article discusses the importance of the gut microbiota, its dysbiosis in patients with hypertension, and potential therapeutic options.
INTRODUCTION: We aimed to estimate the incidence of depression among women of childbearing age between 1990 and 2019 in terms of age, sex, country, and Socio-Demographic Index (SDI). MATERIAL AND METHODS: This study anal...INTRODUCTION: We aimed to estimate the incidence of depression among women of childbearing age between 1990 and 2019 in terms of age, sex, country, and Socio-Demographic Index (SDI). MATERIAL AND METHODS: This study analyzed trends in age-standardized incidence rates (ASIR) and disability-adjusted life years (DALYs) using data from the Global Burden of Disease Study. We calculated the estimated annual percentage change (EAPC) and its corresponding 95% confidence interval (CI). RESULTS: From 1990 to 2019, the ASIR (per 100,000) and age-standardized DALY rate (per 100,000) of depression in women of childbearing age showed a decreasing trend, with EAPC values of -0.53 and -0.44, respectively. Singapore's ASIR and Cuba's age-standardized DALY rate had the lowest EAPC (-2.24 and -2.11). Among the 21 geographical regions, the ASIR and DALY in Central Latin America had the highest EAPC (EAPC of 0.74 and 0.66, respectively), while East Asia had the lowest EAPC (-1.79 and -1.45, respectively). When looking at the changes in ASIR and age-standardized DALY rates from a national perspective, Mexico, Spain, and Germany had the largest increases in ASIR and age-standardized DALY rates. The EAPCs of depression ASIR in women of childbearing age were 1.55, 1.46, and 1.17, respectively, and the EAPCs of depression age-standardized DALY rates in women of childbearing age were 1.40, 1.29, and 1.01, respectively. CONCLUSIONS: From 1990 to 2019, there was a consistent downward trend in the burden of depression in women of childbearing age globally. However, certain countries and regions such as Central Latin America (including Mexico) experienced an upward trend in ASIR and age-standardized DALY rates.
INTRODUCTION: Obesity and weight fluctuations across adulthood are well-documented risk factors for cardiovascular diseases (CVDs), while serum uric acid has emerged as a potential metabolic intermediary influencing card...INTRODUCTION: Obesity and weight fluctuations across adulthood are well-documented risk factors for cardiovascular diseases (CVDs), while serum uric acid has emerged as a potential metabolic intermediary influencing cardiovascular health (CVH). However, limited research has explored the life-stage-specific relationships between weight changes, uric acid levels, and CVH trajectories, particularly the mediating role of uric acid in these associations. MATERIAL AND METHODS: Multivariate linear regression was used to evaluate the associations between weight changes, uric acid levels, and CVH score patterns among 1,257 participants in NHANES cycles (2013-2018). Mediation analysis via bootstrap tests was conducted to investigate the role of uric acid in BMI-CVH relationships across life stages, with stratified analysis by sex. RESULTS: Obesity in early and middle adulthood was significantly associated with lower CVH scores in later adulthood. Weight changes exceeding 2.5 kg and stable obesity from middle to late adulthood were linked to increased cardiovascular risk. Serum uric acid levels were negatively associated with CVH scores and positively correlated with BMI and weight gain across all life stages. Uric acid mediated the relationship between BMI and CVH, with the mediating effect being most pronounced in early adulthood. Notably, this mediation effect showed gender differences, with a consistent effect across all stages in women but being significant only in late adulthood in men. CONCLUSIONS: These findings underscore the complex interplay between weight, uric acid, and cardiovascular health. Maintaining a stable weight and effectively managing uric acid levels, with consideration of sex-specific differences, are critical strategies for improving cardiovascular outcomes across the lifespan.
INTRODUCTION: The aim of the study was to identify gut microbiota (GM) with genetic causal effects on insomnia using Mendelian randomization (MR) and predict potential traditional Chinese medicines (TCMs) for GM-targeted...INTRODUCTION: The aim of the study was to identify gut microbiota (GM) with genetic causal effects on insomnia using Mendelian randomization (MR) and predict potential traditional Chinese medicines (TCMs) for GM-targeted intervention in insomnia. MATERIAL AND METHODS: Summary data from genome-wide association studies (GWAS) on GM and insomnia were obtained from the IEU OpenGWAS database. The R 4.4.1 software, particularly the TwoSampleMR package, was utilized to assess the genetic correlation between GM and insomnia, primarily using the inverse-variance weighted (IVW) method. Functional enrichment analysis was conducted on the genes adjacent to the instrumental variables to explore the signaling pathways through which related GM may mediate insomnia. The CTD and Coremine databases were combined to predict TCM with potential regulatory effects on the genes adjacent to the instrumental variables, and their properties, meridian tropism, and efficacy information were compiled. RESULTS: The MR analysis revealed that Ruminococcaceae and Marvinbryantia were associated with an increased risk of insomnia, while Pasteurellaceae, Olsenella, the Ruminococcus gnavus group, Mollicutes RF9, and Pasteurellales were associated with a decreased risk. The genes adjacent to the instrumental variables were mainly enriched in signaling pathways such as neuroactive ligand-receptor interaction and the mammalian target of rapamycin (mTOR). Representative TCM with high mapping frequencies included Panax ginseng, Curcuma aromatica, Salviae Miltiorrhizae Radix, Zingiber officinale, Glycyrrhizae Radix et Rhizoma, Aucklandiae Radix, Magnoliae Officinalis Cortex, Scutellariae Radix, Ganoderma lucidum, and Poria cocos. CONCLUSIONS: The MR analysis identified seven GM, represented by Ruminococcaceae and Marvinbryantia, that may mediate the occurrence and development of insomnia through signaling pathways such as mTOR and neuroactive ligand-receptor interaction. It predicted potential traditional Chinese medicines that act on GM to intervene in insomnia. This study provided a reference for exploring TCM prevention and treatment strategies for insomnia from the perspective of GM.
INTRODUCTION: Diabetes mellitus (DM) is associated with increased mortality in hospitalized adults. However, data regarding the impact of DM on long-term mortality after discharge in very old patients are scarce. This pr...INTRODUCTION: Diabetes mellitus (DM) is associated with increased mortality in hospitalized adults. However, data regarding the impact of DM on long-term mortality after discharge in very old patients are scarce. This prospective study assessed 3-year post-discharge mortality and its predictive factors in older patients, focusing on possible differences between patients with and without DM. MATERIAL AND METHODS: Medical history, chronic medication use, clinical and laboratory characteristics, Charlson Comorbidity Index (CCI), 5-item Fried Frailty Score (FFS), Clinical Frailty Scale (CFS), Barthel Index (BI), and Katz Index were recorded on admission. RESULTS: A total of 815 older adults (46.0% males) with a median age of 83.0 years (IQR: 77.0-88.0) were included in the study. The 3-year mortality rate was 54.9% in patients with DM ( = 368) and 60.2% in patients without DM ( = 447, = 0.13 between groups). In multivariate logistic analysis, nursing home residency, higher CCI, higher CFS, higher FFS, lower BI, the total number of days of hospitalization in the past year, and hospital-acquired infections were independently associated with the 3-year mortality in both groups. In individuals with DM, lower body mass index (BMI) and elevated urine albumin-to-creatinine ratio (UACR) were identified as additional independent predictors of 3-year mortality. CONCLUSIONS: A high post-discharge mortality rate was observed in very old patients. DM was not identified as an independent factor of post-discharge mortality. Assessment of frailty and disability in very old patients is important for predicting long-term post-discharge mortality. Additionally, in patients with DM, evaluating BMI and UACR may aid in better prediction of 3-year mortality.
INTRODUCTION: The role of mothers has long been the subject of social stereotyping and debate. Psychological and sociological research suggests that women approach this role with a complex ability to multitask, often pri...INTRODUCTION: The role of mothers has long been the subject of social stereotyping and debate. Psychological and sociological research suggests that women approach this role with a complex ability to multitask, often prioritising family care over career development. MATERIAL AND METHODS: For the present study, an anonymous online questionnaire was developed to collect data from 534 female doctors who are mothers ('mother doctors'). The 32-item questionnaire focused on the relationship between their careers and family life, covering demographic information, family configuration, availability of home help, division of household responsibilities and the impact of these factors on their professional life. RESULTS: The study found that the majority of female doctors surveyed (51.7%) stated unequivocally that motherhood had a significant impact on their approach to patients, with 30.7% indicating a moderate impact. The most commonly cited changes at work related to motherhood were a greater understanding of the needs of patients, especially mothers and children (79.1%), as well as increased empathy (59.0%) and changes in communication style (54.7%) with patients. CONCLUSIONS: Motherhood represents a profoundly transformative experience in the professional lives of women doctors, the impact of which goes far beyond stereotypical limitations. Accumulating evidence suggests that mother doctors not only become more organised and resilient to stress, but also develop leadership skills that can contribute to the transformation of the healthcare system in Poland. Childcare challenges are one of the most significant barriers to academic success for mother doctors.
INTRODUCTION: Appropriate levels of physical activity (PA) can help prevent osteoarthritis (OA) and alleviate its symptoms. However, excessive or prolonged PA has been identified as a potential risk factor for OA. Despit...INTRODUCTION: Appropriate levels of physical activity (PA) can help prevent osteoarthritis (OA) and alleviate its symptoms. However, excessive or prolonged PA has been identified as a potential risk factor for OA. Despite these observations, the genetic causal relationship between PA and OA remains unclear. Therefore, this study aimed to clarify the causal link between PA and OA by investigating their shared genetic factors. MATERIAL AND METHODS: The study utilized genome-wide association study (GWAS) summary data to investigate the relationship between three types of PA - moderate to vigorous physical activity (MVPA), vigorous physical activity (VPA) and strenuous sports or other exercises (SSOE) - and knee osteoarthritis (KOA). A two-sample Mendelian randomization (MR) analysis was conducted using the TwoSampleMR and MRPRESSO packages in R. Sensitivity analyses were performed. Cochran's Q statistic and Rucker's Q statistic were employed to assess heterogeneity. The MR-Egger intercept test was used to evaluate horizontal pleiotropy. Additionally, the MR pleiotropy residual sum and outlier (MR-PRESSO) method was applied to detect horizontal pleiotropy and identify outlier SNPs. A leave-one-out analysis was conducted to determine whether the genetic associations were influenced by any single nucleotide polymorphism (SNP). The MR robust adjusted profile score (MR-RAPS) method was further used to validate the normal distribution of the MR analysis. RESULTS: The results of the MR analysis indicate that MVPA ( = 0.436, odds ratio [OR] = 1.814, 95% confidence interval [CI] [0.405-8.119]), VPA ( = 0.995, OR = 1.011, 95% CI [0.040-25.224]) and SSOE ( = 0.266, OR = 0.258, 95% CI [0.024-2.812]) have no significant genetic causal relationship with KOA. We did not detect any heterogeneity or horizontal pleiotropy ( > 0.05), nor were there any outliers in our MR analysis. Our MR results were not driven by a single SNP and were normally distributed ( > 0.05). CONCLUSIONS: The results of this study provide evidence against a genetic causal relationship between PA and KOA, thereby contributing to the understanding of their correlation. However, the study does not rule out the possibility of a relationship through non-genetic mechanisms.
INTRODUCTION: Asthma and chronic obstructive pulmonary disease (COPD) are two common respiratory ailments with an overlapping pathogenesis. MATERIAL AND METHODS: In this study, using a two-sample Mendelian randomization...INTRODUCTION: Asthma and chronic obstructive pulmonary disease (COPD) are two common respiratory ailments with an overlapping pathogenesis. MATERIAL AND METHODS: In this study, using a two-sample Mendelian randomization (MR) approach and analyzing publicly available genome-wide association study (GWAS) datasets, we explored the causal impact of asthma on the onset of COPD. RESULTS: Results: Using genetic instrumental variables associated with asthma ( < 5 × 10) and applying multiple MR methods (IVW, MR-Egger, and weighted median), we identified a significant causal relationship between asthma and COPD. The inverse variance weighted (IVW) method indicated that asthma increases the risk of developing COPD with an odds ratio (OR) of 1.35 (95% confidence interval [CI]: 1.12-1.58, = 0.002). Additionally, multivariable MR analysis was performed to account for potential confounders, such as eosinophil count, smoking, and falls, which demonstrated that the association remains significant even after adjusting for these factors (OR = 1.29, 95% CI: 1.08-1.50, = 0.004). CONCLUSIONS: This study provides robust evidence supporting the causal link between asthma and COPD, offering a more comprehensive understanding of their relationship.
INTRODUCTION: Sepsis arises from dysregulated inflammation in response to infection, precipitating organ dysfunction. Circulating inflammatory mediators likely contribute to sepsis pathogenesis, but their precise roles r...INTRODUCTION: Sepsis arises from dysregulated inflammation in response to infection, precipitating organ dysfunction. Circulating inflammatory mediators likely contribute to sepsis pathogenesis, but their precise roles remain unclear. We aimed to evaluate potential causal impacts of inflammatory proteins on sepsis risk. MATERIAL AND METHODS: We performed a two-sample Mendelian randomization study evaluating causal associations for 91 inflammatory proteins with sepsis risk. Genetic instruments were derived from a published genome-wide association study of plasma proteins. Sepsis outcome data were obtained from the UK Biobank and FinnGen cohort. Inverse-variance weighted analysis was conducted along with several sensitivity analyses. RESULTS: The analyses identified significant causal associations for several inflammatory proteins with sepsis risk. TRAIL exhibited a causal effect on increased overall sepsis risk (OR = 1.10, 95% CI: 1.03-1.17). CCL28 showed a causal link to higher 28-day sepsis mortality in critical care (OR = 3.32, 95% CI: 1.18-9.29). CCL4 demonstrated a causal association with increased 28-day sepsis mortality (OR = 1.81, 95% CI: 1.06-1.31). Meanwhile, beta-NGF was found to be causally protective for sepsis (OR = 0.77, 95% CI: 0.60-0.99), and TNFB also showed a causally protective effect (OR = 0.95, 95% CI: 0.91-1.00). CONCLUSIONS: Our study elucidates roles of inflammatory mediators in sepsis pathogenesis. The identified proteins may serve as biomarkers or therapeutic targets. TRAIL signaling inhibition may hold promise for future clinical translation given its causal links to increased sepsis risk and mortality. CCL28 and CCL4 also represent potential immunological drivers of sepsis mortality worthy of further investigation. Meanwhile, the neurotrophins beta-NGF and TNFB emerged as having protective effects in sepsis that could be therapeutically augmented. Further experimental validation is warranted to confirm the observed causal relationships. Our findings provide targets for future mechanistic and clinical examination to impact patient prognosis.
Ensuring an adequate supply of essential micronutrients while preventing excessive intakes that could lead to adverse effects presents a challenge in the context of food supplement regulation, in the absence of harmoniza...Ensuring an adequate supply of essential micronutrients while preventing excessive intakes that could lead to adverse effects presents a challenge in the context of food supplement regulation, in the absence of harmonization in the European Union. This paper examines the scientific rationale and regulatory frameworks governing the definition of maximum allowable levels for vitamins and minerals in food supplements. Existing legislation, scientific literature, and institutional documents were considered, focusing on the different factors influencing the risk-benefit assessment, such as dietary habits, selection of the reference population, and the contribution of fortified and enriched foods to total nutrient intake. While a precautionary approach has been proposed to prevent potential risks linked to excessive intakes, too restrictive limits may undermine the nutritional role of supplementation. Future regulatory frameworks should integrate both safety and efficacy considerations, ensuring that supplements contribute meaningfully to micronutrient adequacy while preventing excessively high intake levels.
INTRODUCTION: Plasma concentrations of cell-free DNA (cfDNA) serve as markers of overtraining or muscle injury. We examined whether nuclear (n) or mitochondrial (mt) cfDNA has potential as a marker of muscle burden or da...INTRODUCTION: Plasma concentrations of cell-free DNA (cfDNA) serve as markers of overtraining or muscle injury. We examined whether nuclear (n) or mitochondrial (mt) cfDNA has potential as a marker of muscle burden or damage. MATERIAL AND METHODS: Ten healthy, physically active volunteers (6 females, aged 27.1 ±6.8 years) performed a downhill running test. Samples for cfnDNA and cell-free mitochondrial DNA (cfmtDNA) analysis were collected before, 30 min, 1 h, and 14 days after the downhill run. CfnDNA and cfmtDNA (two markers for each) were analyzed using qPCR. RESULTS: There was an extreme (~40-fold) increase in cfnDNA at the 30-min time-point against the baseline ( < 0.00001 for both markers), followed by a quick drop to baseline levels after 1 h after the end of the downhill run for all subjects. In contrast, plasma levels of cfmtDNA did not increase significantly ( = 0.27 and 0.12). It reflects the fact that in 6 subjects, the pattern was similar as for cfnDNA, but in 4 subjects a decrease of cfmtDNA concentration was observed at the 30-min time-point. These differences correlate with age, body mass index, and sex of the participants. Plasma cfnDNA significantly ( < 0.01 for all) correlated with concentrations of muscle damage markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LD), and chemokines MIP-1α and IP-10 (positive). No homogeneous correlation between cfmtDNA and biomarkers was detected. CONCLUSIONS: Our study confirmed the extreme release and clearance of cfnDNA in physically active subjects after strenuous exercise. In contrast, the trajectory of cfmtDNA concentrations seems to have much higher inter-individual variability than cfnDNA concentrations.
INTRODUCTION: Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC). Epidemiological studies have found that patients with IBD are more likely to suffer from cardiovascular diseases (...INTRODUCTION: Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC). Epidemiological studies have found that patients with IBD are more likely to suffer from cardiovascular diseases (CVDs) than the general population. However, so far, no exact causal association has been demonstrated between IBD and CVDs, and more research is needed to clarify this relationship. MATERIAL AND METHODS: The two-sample Mendelian randomization (MR) method was used to explore the causal effect of IBD on CVDs. The exposure factor was IBD, including CD and UC. The outcome was CVDs, including chronic heart failure, atrial fibrillation, coronary heart disease, myocardial infarction and hypertension. The single nucleotide polymorphisms (SNPs) are all from the FinnGen genome-wide association study sample database. The CD samples included 210,300 controls and 807 cases, and the UC samples included 215,806 controls and 2701 cases. The samples included are all European samples. SNPs associated with Crohn's disease and ulcerative colitis were extracted from the IEUGWAS database and quality control and screening were carried out. Inverse variance weighted (IVW), MR-Egger, weighted median and other methods were used to study the causal relationship between them and CVDs. Finally, Cochrane's Q test, MR-Egger and the leave-one method were used for sensitivity analysis. RESULTS: In this study, 4 SNPs strongly associated with Crohn's disease and 12 SNPs strongly associated with ulcerative colitis were screened. The IVW method of genetic prediction revealed a positive correlation between Crohn's disease and the risk of chronic heart failure (OR =1.02; 95% CI: 1.00-1.04), and there was a positive correlation between ulcerative colitis and the risk of chronic heart failure (OR = 1.03; 95% CI: 1.00-1.06). IVW, MR-Egger and weighted median showed that Crohn's disease and ulcerative colitis were not associated with the risk of atrial fibrillation, coronary heart disease, myocardial infarction or hypertension. Sensitivity analysis showed that the results are robust. CONCLUSIONS: Crohn's disease and ulcerative colitis are associated with an increased risk of chronic heart failure, but they are not associated with the risk of other CVDs.