Large-scale Epidemiological Studies Research Articles

Sleep Disorders and Sleep Studies Case Reports

Sleep disorders represent a significant public health concern due to their widespread prevalence, impact on overall health, and the economic burden they impose. These disorders encompass a broad spectrum of conditions, ranging from insomnia and obstructive sleep apnea (OSA) to narcolepsy, restless legs syndrome (RLS), and parasomnias. They are often associated with comorbidities such as cardiovascular diseases, metabolic dysfunctions, and mental health disorders, making their identification and management critical. The publication of this work is of high interest as it contributes to the expanding body of literature focused on understanding the complex interplay between sleep disorders and health outcomes. By presenting detailed case reports, this study provides valuable insights into the diagnostic challenges, treatment modalities, and potential avenues for personalized interventions in sleep medicine. Case reports are particularly important in this field as they shed light on unique presentations and rare conditions that might otherwise go unnoticed in large-scale epidemiological studies. From an epidemiological perspective, sleep disorders are highly prevalent globally. According to the World Health Organization (WHO), approximately 30% - 45% of the global population experiences sleep disturbances. Obstructive sleep apnea, for instance, affects nearly 1 billion individuals worldwide, with varying prevalence across age, gender, and geographic regions. Insomnia affects roughly 10% - 30% of adults, with rates as high as 50% - 60% in older populations. Meanwhile, narcolepsy, though rare, is estimated to affect 1 in 2,000 people in the general population. These statistics underscore the pressing need for enhanced diagnostic methods, improved treatment strategies, and comprehensive patient management. By detailing real-world cases, this publication aims to bridge the gap between clinical observations and broader scientific understanding. The insights gained from these case studies have the potential to inform future research directions, improve clinical practices, and ultimately enhance patient outcomes in sleep medicine. Sleep disorders affect millions of individuals globally, disrupting physical, mental, and emotional well-being. Conditions such as insomnia, obstructive sleep apnea (OSA), narcolepsy, and restless legs syndrome (RLS) are among the most studied. This paper examines the etiology, diagnosis, and management of sleep disorders, presenting detailed case reports and integrating relevant sleep study findings. Figures such as polysomnography (PSG) outputs and statistical trends provide visual insights into diagnostic and therapeutic interventions. Sleep disorders encompass a wide range of conditions that significantly disrupt sleep quality and overall well-being. Common disorders such as insomnia, obstructive sleep apnea (OSA), narcolepsy, and restless legs syndrome (RLS) affect millions globally, posing risks to physical health, mental stability, and cognitive performance. This study explores the clinical presentation, diagnostic approaches, and management of sleep disorders through the lens of detailed case reports and sleep study data. Polysomnography (PSG), the gold standard for sleep disorder diagnosis, plays a pivotal role in identifying abnormal sleep patterns, respiratory irregularities, and neural disruptions. Multiple sleep latency tests (MSLT) and actigraphy complement PSG, offering insights into disorders like narcolepsy and circadian rhythm abnormalities. This paper presents three representative case reports: chronic insomnia, severe OSA, and narcolepsy with cataplexy. Each case is analyzed in-depth, highlighting patient history, PSG findings, treatment interventions, and outcomes. For chronic insomnia, cognitive-behavioral therapy for insomnia (CBT-I) and pharmacological intervention resulted in marked improvements in sleep latency and efficiency. In the OSA case, continuous positive airway pressure (CPAP) therapy significantly reduced the apnea-hypopnea index (AHI) and alleviated daytime symptoms. The narcolepsy case demonstrates the efficacy of modafinil and sodium oxybate in managing excessive daytime sleepiness and cataplexy. Despite advancements, challenges persist in the field, including patient adherence to therapy, accessibility to specialized sleep studies, and the ethical implications of AI-driven diagnostic tools. Future research should focus on scalable, patient-centric approaches and the role of emerging technologies in enhancing diagnostic accuracy and treatment efficacy. This paper aims to contribute to the evolving understanding of sleep disorders, bridging clinical case insights with the broader implications for sleep health and research.

Impaired brainstem auditory evoked potentials after in utero exposure to high dose paracetamol exposure

Paracetamol is an analgesic and antipyretic medication regarded as the safest over-the-counter pain and fever relief option during pregnancy. Paracetamol and its metabolites are known to reach the developing fetus through direct placental transfer and can cross the blood brain barrier. Several recent, large-scale epidemiologic studies suggest that in utero paracetamol exposure can increase the risk of neurodevelopmental conditions, including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and developmental delay (DD). Since auditory processing deficits are a common feature of ASD, we hypothesized that animals exposed to paracetamol in utero will have impaired auditory brainstem function. We investigated this hypothesis by recording and analyzing click-evoked auditory brainstem responses (ABR) at postnatal day 21 and 29 in Sprague-Dawley rats. In utero exposure to high dose paracetamol exposure had no impact on body or brain weight. However, high dose paracetamol exposure did significantly delay ear opening and resulted in elevated ABR thresholds, and longer wave and interwave latencies. These changes in wave latency extended to the highest click intensity tested but were most severe near threshold. This data suggests that development and function of the auditory brainstem may be impacted by high dose paracetamol exposure and that simple, non-invasive tests of auditory function have utility as an early screening tool for neurodevelopmental disorders.

The Impact of Blood Lead and Its Interaction with Occupational Factors and Air Pollution on Hypertension Prevalence

Large-scale epidemiological studies on the association of blood lead levels with blood pressure and hypertension prevalence are still limited, particularly among lead-exposed workers. The evidence is even more scarce on the interaction of blood lead levels with occupational variables and ambient air pollution levels. We developed mixed-effect models based on a large group of lead-exposed workers (N = 22,002). The results were also stratified by multiple groupings. Compared to participants with blood lead < 20 μg/L, those with levels > 20 μg/L had a 26–37% higher prevalence of hypertension, as well as a 0.65–13.7mmHg higher systolic and diastolic blood pressure. Workers exposed to high PM10 levels had a 21–28% higher risk. Workers exposed to high temperatures had a 0.41–2.46 mmHg greater increase in blood pressure, and those not exposed to dust had a 1.29–1.65 mmHg greater blood pressure increase. Our findings suggested the negative impact of blood lead on blood pressure and the prevalence of hypertension, with workers exposed to high PM10 concentrations, those exposed to occupational high temperature, and those without dust exposure being more vulnerable.

Database study of risk factors for breast cancer-related lymphedema: a statistical analysis of 2359 cases over 10years.

Identifying risk factors for breast cancer-related lymphedema (BCRL) is crucial for its prevention, necessitating large-scale epidemiological studies. Despite their suitability for large-scale surveys, to our knowledge, databases have not been the basis of any study done to investigate BCRL risk factors. This study aimed to test the hypothesis that a database-based study would be useful for identifying BCRL risk factors. Patients with breast cancer diagnosed between April 2009 and March 2020 were identified from the Hiroshima University Hospital's medical database. This retrospective observational study validated the risk factors for BCRL using logistic regression analysis (p < 0.05). Among the total 4471 breast cancer patients identified, 2359 met the study criteria, with a BCRL incidence of 4.8%. Identified risk factors included obesity with a BMI of 25-30 (OR = 3.066, 95% CI 1.408-6.677), severe obesity with a BMI > 30 (OR = 5.791, 95% CI 2.239-14.97), surgical axillary lymph node dissection (OR = 3.212, 95% CI 1.918-5.378), chemotherapy with docetaxel (OR = 1.795, 95% CI 1.062-3.032), and conventional radiation to the breast or chest wall including lymph nodes in the irradiated area (OR = 3.299, 95% CI 1.842-5.910). The BCRL risk factors identified by our database analysis were in line with those documented in previous studies, indicating the usefulness of database-based studies. Future studies should include more patients and study items.

Multicentre Study of Candida parapsilosis Blood Isolates in Türkiye Highlights an Increasing Rate of Fluconazole Resistance and Emergence of Echinocandin and Multidrug Resistance.

Worldwide emergence of clonal outbreaks caused by fluconazole-resistant (FLCR) and the recent emergence of echinocandin- and multidrug-resistant (ECR and MDR) Candida parapsilosis isolates pose serious threats to modern clinics. Conducting large-scale epidemiological studies aimed at determining the genetic composition and antifungal resistance rates is necessary to devise antifungal stewardship and infection control strategies at international, national and local levels. Despite being severely hit by outbreaks due to FLCR C. parapsilosis isolates, such knowledge at the national level is lacking in Türkiye. Herein, we conducted a prospective multicentre study involving five major clinical centres in Türkiye to determine antifungal resistance rates, underlying mechanisms and genetic composition of all isolates. In total, 341 isolates were collected from 265 patients including clinical information. Antifungal susceptibility testing against common antifungals was performed in addition to sequencing of ERG11 and FKS1. Last, isolates were genotyped with short tandem repeat (STR) genotyping to investigate potential nosocomial transmission. The FLCR rate was 26.7% (91/341), out of which 75.8% (69/91) harboured the ERG11Y132F mutation. Patients infected with FLCR isolates had a higher mortality rate compared to their susceptible counterparts (49% for FLCR vs. 42% for susceptible). ECR rate was 2.1% (7/341) and isolates carried FKS1F652L/R658G/W1370R mutations. Concerningly, four ECR isolates were MDR. FLCR isolates grouped in distinct clusters without evidence of inter-hospital transmission, whereas large clusters containing susceptible isolates from all centres were noted. Overall, the increasing prevalence of FLCR C. parapsilosis at national level and the emergence of ECR and MDR isolates pose serious clinical challenges in Türkiye. Therefore, conducting large-scale epidemiological studies are critical to determine the trend of antifungal resistance and to tailor pertinent antifungal stewardship and infection control strategies to effectively curb the spread of drug-resistant C. parapsilosis.

Serum from Hypertensive Patients Induces Cancer-Supporting Phenotype of Vascular Endothelium In Vitro.

Large-scale epidemiological studies have established a bidirectional association between hypertension and cancer. However, the underlying mechanisms explaining this connection remain unclear. In our study, we investigated whether serum from patients with hypertension (HT) could enhance the aggressiveness of cancer cells in vitro through alterations in endothelial cell phenotype. Experiments were performed using EAhy926 endothelial cells and ovarian (SKOV-3), colorectal (SW480), pancreatic (PSN-1), breast (MCF-7), and lung (A549) cancer cell lines. This study showed that conditioned medium (CM) produced by EAhy926 cells, when exposed to serum from patients with untreated hypertension (HT-CM), promotes the proliferation, migration, and invasion of every cancer cell line tested. In addition, endothelial cells subjected to HT serum promote the adhesion of all cancer cell types except PSN-1. An intensified transendothelial invasion of cancer cells was accompanied by decreased expression of junctional proteins (connexin 43, E-cadherin, occluding, desmoglein) in HT serum-treated endothelial cells. Quantitative analysis of the secretome of endothelial cells subjected to HT serum showed that they secrete increased amounts of CCL2, CXCL1, CXCL8, bFGF, HGF, IL-6, PAI-1, and TGF-β1. Moreover, cancer cells exposed to HT-CM display increased mRNA expression for several pro-cancerogenic agents, including CXCL8, tPA, and VEGF. Our report shows that hypertension may potentiate cancer cell aggressiveness by modulating endothelial cell phenotype. Further tests with antihypertensive drugs are required to assess whether effective treatment of hypertension can mitigate its cancer-promoting potential.

Genetic Risk Scores for the Clinical Rheumatologist.

The advent of genome-wide sequencing and large-scale genetic epidemiological studies has led to numerous opportunities for the application of genetics in clinical medicine. Leveraging this information toward the formation of clinically useful tools has been an ongoing research goal in this area. A genetic risk score (GRS) is a measure that attempts to estimate the cumulative contribution of established genetic risk factors toward an outcome of interest, taking into account the cumulative risk that each of these individual genetic risk factors conveys. The purpose of this perspective is to provide a systematic framework to evaluate a GRS for clinical application. Since the initial polygenic risk score methodology in 2007, there has been increasing GRS application across the medical literature. In rheumatology, this has included application to rheumatoid arthritis, gout, spondyloarthritis, lupus, and inflammatory arthritis. GRSs are particularly relevant to rheumatology, where common diseases have many complex genetic factors contributing to risk. Despite this, there is no widely accepted method for the critical application of a GRS, which can be a particular challenge for the clinical rheumatologist seeking to clinically apply GRSs. This review provides a framework by which the clinician may systematically evaluate a GRS. As genotyping becomes more accessible and cost-effective, it will become increasingly important to recognize the clinical applicability of GRSs and identify those of the highest utility for patient care. This framework for the evaluation of a GRS will also help ensure reliability among GRS research in rheumatology, thereby helping to advance the field.

Molecular and serological diagnosis of the circulating Trypanosoma evansi in Egyptian livestock with risk factors assessment

This study aimed to characterize and determine the prevalence and the associated risk factors of trypanosomiasis in different Egyptian livestock from various governorates using molecular and serological techniques, adding to an assessment of some biochemical alterations in serum samples. A total 1019 blood samples were collected from nine governorates in the period from January 2020 to September 2021 from cattle (n = 752), buffaloes (n = 42), sheep (n = 65), goats (n = 60), donkeys (n = 54), and horses (n = 46). Molecular investigation followed by sequencing confirmed the presence of only Trypanosoma evansi (T. evansi) infection with a prevalence rate of 3.73 % (38/1019). Serologically, T. evansi was detected by indirect ELISA in 11 samples out of 519 negative PCR ones, with an overall prevalence 2.1 %. Furthermore, statistical difference was found between investigated governorates in both molecular and seroprevalence. Surprisingly, the risk of T. evansi infection was significantly (P < 0.05) higher in winter (9.83 %) than in autumn (1.4 %), while no infection was recorded in the spring and summer seasons. No significant difference regarding animal hosts, age, and sex as risk factors was recorded. Serum biochemical analysis showed a non-significant decrease of total proteins, albumin, A/G ratio, and HDL-cholesterol in cattle, equine, and goats with a non-significant increase in total globulins level. In sheep, a significant increase was determined in all tested parameters except a significant decrease in the level of albumin and A/G ratio. To the best of our knowledge, this is the first large-scale epidemiological study determining the endemicity of the neglected T. evansi infection in different animal species in multiple governorates of Egypt. It is recommended to use both molecular and serological techniques for efficient diagnosis of trypanosomiasis as a preliminary approach to control the disease.

John Schulenberg as a developmental scholar and mentor: Personal reflections.

John Schulenberg has had significant impact on developmental science. His conceptual writing and empirical research, grounded in developmental contextualism, emphasized the critical role that developmental transitions play in shaping health risks, especially substance use, across the life course. Schulenberg's integration of developmental concepts with large-scale epidemiological studies, particularly through his leadership in the Monitoring the Future study, provides key insights into how significant life changes-such as school transitions, employment, and relationships-interact to influence well-being across adolescence and early adulthood. He was a fierce advocate for adolescence and young adulthood being critical phases of life, deserving of focused attention and support. John was also a devoted mentor to the next generation of developmental scientists. This commentary reflects on John Schulenberg's legacy, highlighting five of his foundational concepts (developmental tasks, transitions, trajectories, turning points, and timing) and celebrating his role as a generative and joyful mentor. He fostered open intellectual dialog, promoted and celebrated career development, and took pleasure in life inside and outside work, helping early career scientists to develop innovative and impactful research programs. Schulenberg's commitment to positive relationships and celebrating success is an enduring model for future generations of developmental scientists and mentors.

Evaluating vitamin D status in Chinese pre-school children using dried blood spots coupled with liquid chromatograph coupled with mass spectrometer.

Vitamin D is an essential micronutrient for multiple physiological processes, and its deficiency remains a world-wide public health problem that cannot be ignored. Dried blood spot (DBS) is a convenient tool in large-scale epidemiological studies, but its application in evaluating vitamin D status in Chinese population is still scarce. Herein, we aimed to determine the vitamin D status in Chinese pre-school children using DBS coupled with LC-MS/MS method. We first developed a sensitive and reliable method for the determination of 25-hydroxyvitamin D (25(OH)D) in DBS samples using an ultra-high-performance liquid chromatograph coupled with triple quadrupole mass spectrometer (UHPLC-QQQ-MS/MS). Next, we conducted a pilot study to compare the 25(OH)D concentration in DBS and serum samples. Finally, the assay method was used to evaluate vitamin D status in Chinese pre-school children. The present method was validated to be reliable and robust for the determination of 25(OH)D in DBS samples. Comparable consistency was observed between the 25(OH)D concentration in DBS and serum samples. A total of 3826 DBS samples collected from children aged 1-7 years were determined. The median concentration of 25(OH)D was 19.57 ng/mL (interquartile range 14.73-24.36 ng/mL), and decreased from 1 to 7 years of age. In addition, 13.51% of male children and 15.12% female children are found to be deficient in 25(OH)D. DBS coupled with LC-MS/MS is a feasible strategy to evaluate vitamin D status in epidemiological studies. And vitamin D deficiency remains a common health problem in Chinese pre-school children.

Investigating Exposure and Hazards of Micro- and Nanoplastics During Pregnancy and Early Life (AURORA Project): Protocol for an Interdisciplinary Study.

Micro- and nanoplastics (MNPs) are emerging pollutants of concern with ubiquitous presence in global ecosystems. MNPs pose potential implications for human health; however, the health impacts of MNP exposures are not yet understood. Recent evidence suggests that MNPs can cross the placental barrier, underlying the urgent need to understand their impact on reproductive health and development. The Actionable eUropean ROadmap for early-life health Risk Assessment of micro- and nanoplastics (AURORA) project will investigate MNP exposures and their biological and health effects during pregnancy and early life, which are critical periods due to heightened vulnerability to environmental stressors. The AURORA project will enhance exposure assessment capabilities for measuring MNPs, MNP-associated chemicals, and plastic additives in human tissues, including placenta and blood. In this interdisciplinary project, we will advance methods for in-depth characterization and scalable chemical analytical strategies, enabling high-resolution and large-scale toxicological, exposure assessment, and epidemiological studies. The AURORA project performs observational studies to investigate determinants and health impacts of MNPs by including 800 mother-child pairs from 2 existing birth cohorts and 110 women of reproductive age from a newly established cohort. This will be complemented by toxicological studies using a tiered-testing approach and epidemiological investigations to evaluate associations between maternal and prenatal MNP exposures and health perturbations, such as placental function, immune-inflammatory responses, oxidative stress, accelerated aging, endocrine disruption, and child growth and development. The ultimate goal of the AURORA project is to create an MNP risk assessment framework and identify the remaining knowledge gaps and priorities needed to comprehensively assess the impact of MNPs on early-life health. In the first 3 years of this 5-year project (2021-2026), progress was made toward all objectives. This includes completion of recruitment and data collection for new and existing cohorts, development of analytical methodological protocols, and initiation of the toxicological tiered assessments. As of September 2024, data analysis is ongoing and results are expected to be published starting in 2025. As plastic pollution increases globally, it is imperative to understand the impact of MNPs on human health, particularly during vulnerable developmental stages such as early life. The contributions of the AURORA project will inform future risk assessment. DERR1-10.2196/63176.

A rapid economical multiplex PCR-RFLP method for molecular detection and genotyping of Giardia duodenalis clinical isolates

Giardia duodenalis is a common cause of diarrheal illness in regions with limited resources. The demand for rapid and cost-effective detection and genotyping methods in large-scale epidemiological studies and clinical diagnostics is imperative. Hence, we developed a multiplex PCR-RFLP technique targeting the tpi gene of G. duodenalis. The assay successfully screened G. duodenalis positive clinical samples (6.33 %; 36/565). It was also able to categorize the isolates into assemblages A (41.66 %; 13/36) and B (58.33 %; 23/36), as well as into subassemblages: AI (13.8 %; 5/36), AII (27.77 %; 10/36), BIII (36.11 %; 15/36) and BIV (22.22 %; 8/36). High diagnostic sensitivity (94.2 %), specificity (100 %) and accuracy (97.1 %) of the PCR assay were obtained, indicating its reliability for diagnosing giardiasis. Notably, the assay demonstrated close concordance with microscopy (κ=0.85) and reference PCR (κ=0.98) results. The optimized method offers a cost-effective and rapid approach for G. duodenalis detection and genotyping, convenient for epidemiological studies and clinical diagnostics.

B-021 Impact of Assay Conditions on FT4 Measurement Accuracy of Equilibrium Dialysis LC/MS/MS Clinical Assay

Abstract Background Reliable FT4 measurements are vital for accurate diagnosis and effective management of thyroid disorders. However, currently used FT4 immunoassays (IAs) lack standardization, leading to significant variations between platforms. Equilibrium dialysis (ED) coupled with LC-MS/MS analysis, considered the gold standard for FT4 measurement, has been adopted as a reference measurement procedure (RMP) for IA standardization. This study aimed to establish a high-throughput version of the routine clinical FT4 assay based on ED-LC/MS/MS technology and assess the impact of altered assay conditions on measurement accuracy. Methods A commercially available micro-ED plate was employed for ED-LC/MS/MS analysis. FT4 extraction from the dialysate was performed by utilizing a 96-well C18 SPE plate, followed by FT4 quantitation via LC-MS/MS in positive ion mode. Certified primary reference material was used to calibrate the assay. To evaluate assay robustness, the effects of minor method modifications were studied, including incubation time of ED, serum/buffer ratios in ED inserts, ED incubation temperature, shaker speed during ED, serum sample dilution ratio, and dialysate sample dilution ratio. Additionally, short-term and long-term stability of serum FT4 were assessed. Results The developed ED-LC/MS/MS assay successfully resolved T4, T3, reverse triiodothyronine (rT3), and other interferences within 4 minutes using C18 chromatography. The assay's linear range (0.5-100 pg/mL) encompassed clinically relevant FT4 concentrations across hypo- and hyperthyroid patient samples. Excellent agreement was observed between the routine assay based on ED-LC/MS/MS and CDC RMP with a Deming regression slope near 1 (95%CI: 0.87-1.06). Furthermore, serum/buffer ratios from 1:1 to 1:2.5 in ED inserts, shaker speeds from 75 to 150 rpm, and ED incubation times from 16 to 20 hours did not significantly affect FT4 measurement. However, elevated ED temperature (38°C) led to a more than 10% increase in FT4 values. Serum FT4 remained stable when exposed to room temperature for 12 hours, five freeze-thaw cycles, and -70°C storage for 1.5 years. Additionally, dilution of sera by up to 3-fold before ED did not alter FT4 measurement results. Diluting dialysate samples at least 3 times prior to SPE extraction proved accurate for samples exceeding the calibration curve range. Conclusions In conclusion, we successfully developed a routine clinical FT4 assay based on ED-LC/MS/MS that generates data comparable to the RMP. The assay exhibits robustness, with several altered conditions not significantly impacting measurement accuracy. This high-throughput and accurate assay demonstrates suitability for both clinical laboratories and large-scale epidemiological studies. Disclaimer: The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. Use of trade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention, the Public Health Service, and the US Department of Health and Human Services.

Effect of leptin and adiponectin on the expression of cytokine genes IL-1β, IL-6 AND TNFα in lymphocytes

Metabolic syndrome (MS) is one of the world’s topical health problems. Large-scale epidemiological studies on the prevalence of MS in the world have not been conducted, but according to different authors, depending on the region of residence, the composition of the study population and the diagnostic criteria used, the incidence of MS is at least 10%, and according to estimates of the International Diabetes Federation IDF – up to 25% of the adult population. The metabolic changes in MS are explained by a disturbance in the balance of mediators synthesized by adipose tissue (adiponectin, leptin, resistin, visfatin, vaspin and others); MS is also considered as a subclinical chronic inflammatory process characterized by excessive synthesis of proinflammatory and deficiency of anti-inflammatory cytokines. According to modern ideas, changes in the cellular and humoral immunity in MS are largely due to the imbalance of adipokines: leptin and adiponectin. Increased functional activity of immune cells, including lymphocytes, leads to changes in cytokine gene expression. In the present work, we studied in vitro the expression of IL-1â, IL-6 and TNFá genes in peripheral blood lymphocytes under the influence of adipokines at concentrations characteristic of MS. As a result, differential effects of adipokines on lymphocytes of MS patients and conditionally healthy individuals were found. In conditionally healthy individuals, incubation of lymphocytes with adipokines leptin, adiponectin and their combination, as well as in the presence of physiological solution causes an increase in IL-6 gene expression. The most noticeable effect was observed when cultured with adiponectin. Thus, in norm, with a decrease in the physiological concentration of adiponectin, the expression of IL-6 in lymphocytes increases, indicating insufficient realization of the anti-inflammatory effect of adiponectin. In MS, IL-6 gene expression increases in lymphocytes isolated from peripheral blood in vitro after incubation with adiponectin, a combination of adiponectin and leptin, as well as in the presence of physiological solution. No changes in IL-6 gene expression under the effect of high concentration of leptin were detected. Probably, our results reflect the phenomenon of lymphocyte resistance to leptin action in MS, as under its influence there is not activation of lymphocytes characteristic in vivo, but on the contrary, decrease of activated subpopulations, also there is no change in IL-6 gene expression. Thus, adipokines in concentrations characteristic of metabolic syndrome influence the functional activity of peripheral blood lymphocytes.

Per-and polyfluoroalkyl substances and disrupted sleep: mediating roles of proteins

BackgroundPer-and polyfluoroalkyl substances (PFAS) contamination may disrupt sleep through disrupted metabolic and immune functions. The study aims to investigate the association and potential mechanism between PFAS and sleep. MethodsWe included 136 young adults recruited between 2014-2018 and 76 were re-assessed between 2020-2022. Additional 8 participants only had complete data between 2020-2022. Plasma PFAS (PFOS, PFOA, PFHxS, PFHpS, PFPeS, PFNA, PFDA) were measured at both visits using liquid-chromatography high-resolution mass spectrometry. Plasma proteins were measured by Olink® Explore 384 Cardiometabolic and Inflammation Panel I. Sleep duration was self-reported at both visits along with follow-up sleep disturbance and sleep-related impairment using validated instruments. We utilized multiple linear regression to explore the association between individual PFAS (in tertile) and these sleep outcomes. PFAS associated with sleep outcomes were subjected to computational toxicology analysis using the Comparative Toxicogenomics Database and Toxicology in the 21st Century database to identify potential genetic links between them. Mediation analysis using proteomic data was then performed to confirm the findings from computational toxicology analysis. ResultsAt baseline, one tertile increase in PFDA was associated with 0.39 (95 % CI: 0.05, 0.73) hours of shorter nightly sleep duration, and, at follow-up, PFHxS and PFOA were associated with 0.39 (95 % CI: 0.05, 0.72) and 0.32 (95 % CI: 0.01, 0.63) hours shorter sleep duration, respectively. One tertile increase in PFOS exposure was associated with a 2.99-point increase in sleep disturbance scores (95 % CI: 0.67, 5.31) and a 3.35-point increase in sleep-related impairment scores (95 % CI: 0.51, 6.20). Computational toxicology and mediation analyses identified potential mediating roles for several proteins in the PFAS-sleep associations, including 11-beta-dehydrogenase isozyme 1 (HSD11B1), cathepsin B (CTSB) and several immune system-related proteins. ConclusionFuture large scale epidemiological and mechanistic studies should confirm our findings and test effect measure modification of the associations by age.

Biological monitoring of exposure to benzene in water pipe smokers of rural Western Uttar Pradesh (India)

Aim: Present study was performed to investigate the possible human exposure to benzene through water pipe smoking, if any, in the selected rural population of Western Uttar Pradesh. Methodology: Urine samples from water pipe smokers of both the sexes were collected and analyzed for urinary concentration of phenol, creatinine and malondialdehyde employing standard methods. Results: The results showed that tobacco used by selected rural population contained traces of benzene in the range of 2.75 to 9.682µl ml-1. Analysis of urine samples for phenol, a major metabolite of benzene, showed its increased concentrations in water pipe smokers than non smokers. Further, the effects of age and gender differences on the excretion of phenol were also recorded. Female water pipe smokers were found to be more vulnerable to benzene exposure than male smokers. Intriguingly, alcoholic water pipe smokers were less vulnerable than the non-alcoholic smokers. Interpretation: It is concluded that respiratory, cardiac and haematological disorders caused by water pipe smoking might be attributed to long term benzene exposure amongst water pipe smokers. Large scale epidemiological studies are warranted in Indian rural population considering WHO (Framework Convention on Tobacco Control) regulations of water pipe smoking and tobacco products. Key words: Biological monitoring, Benzene, Oxidative stress, Phenol, Tobacco, Waterpipe smoking

Sarcopenia in the era of precision health: Toward personalized interventions for healthy longevity.

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, significantly impacts health outcomes in older adults. This review explores the evolving landscape of sarcopenia research, with a particular focus on its unique characteristics in Asian populations and emerging pharmaceutical interventions. Recent studies have revealed distinct patterns of muscle mass decline in Asian adults, particularly in women, challenging the universal application of global sarcopenia diagnostic criteria. The Asian Working Group for Sarcopenia has proposed region-specific diagnostic criteria, acknowledging these ethnic variations. Prevalence estimates of sarcopenia vary widely, ranging from 10% to 40% in community-dwelling older adults. For specific chronic conditions, the prevalence of sarcopenia is notably higher, reaching 35% for cardiovascular diseases and 24.5% for chronic kidney disease. Sarcopenia is strongly associated with various chronic conditions, increasing the risk of falls by 1.5 to 3 times and significantly increasing mortality risk by 29% to 51%. Current management strategies primarily involve resistance exercise and nutritional interventions, with a recommended daily protein intake of at least 1.2 g/kg to maintain muscle health. Pharmaceutical development has gained significant momentum, with over 20 compounds in various stages of clinical trials. These include myostatin inhibitors, selective androgen receptor modulators, ghrelin receptor agonists, mesenchymal stem cell therapy, and follistatin gene therapy. However, the unique dietary patterns, cultural contexts, and potentially distinct drug responses in Asian populations necessitate tailored interventions and Asia-specific clinical trials. Future directions include refining Asian-specific diagnostic criteria, conducting large-scale epidemiological studies across multiple Asian countries, developing culturally appropriate interventions, integrating sarcopenia management into chronic disease care, and advancing pharmaceutical research with a focus on Asian populations. In conclusion, sarcopenia emerges as a critical nexus in the aging process, intricately linked with multiple organ systems and chronic conditions, underscoring the imperative for its recognition as a cornerstone in person-centered care and the holistic management of age-related health challenges.

Predictors of sleepiness in a large-scale epidemiology study ESSE-RF.

To identify predictors of excessive daytime sleepiness we analyzed data from the 'Epidemiology of cardiovascular diseases in regions of Russia (ESSE-RF)' study. Data from participants of the cohort study ESSE-RF (2012-2013), aged 25-64 years, from 13 regions of Russia were analyzed (2012-2013). The participants were interviewed regarding their sleep complaints, including difficulties with initiating and maintaining sleep, sleepiness, and use of sleeping pills. Sleepiness was considered significant if it occurred at least three times a week. The examination encompassed social, demographic, and anthropometric measures, lifestyle factors, self-reported diseases, and laboratory parameters. The final analysis included 13,255 respondents. Frequent (≥3 times/week) sleepiness was reported by 5,8%, and occasional sleepiness (1-2 times/week) by 10.8% of respondents. Multivariate regression analysis identified significant predictors of frequent sleepiness. Sleep complaints (insomnia, sleep apnea, snoring) and frequent use of sleep medication were prominent factors. Additionally, age, female gender, higher education, and retirement status were associated with sleepiness. Beyond demographics and sleep, the analysis revealed predictors: abnormal anxiety levels, low high-density lipoprotein, high salt intake and following medical conditions: arrhythmia, hypertension, myocardial infarction, other heart diseases, and renal disease. This study identified a significant prevalence of EDS in Russians, aligning with global trends. However, findings suggest potential regional variations. Analysis revealed a complex interplay of factors contributing to EDS, highlighting the importance of individualized treatment approaches for improved sleep health.

Cost-Utility Analysis of Stereotactic Body Radiation Therapy Versus Surgery for Patients With Stage I Non-small Cell Lung Cancer in Japan.

Stereotactic body radiation therapy (SBRT) for patients with operable stage I non-small cell lung cancer (NSCLC) is less invasive than surgery. However, differences in lifetime costs and patient outcomes remain unclear. In this study, a cost-utility analysis of SBRT compared with surgery for Japanese patients with operable stage I NSCLC was conducted. A partitioned survival model was constructed using each treatment arm's overall survival (OS) and progression-free survival (PFS) data. The data for the SBRT arm were extracted from the Japanese multicenter cohort study, which enrolled 678 medically operable patients with stage I NSCLC, and patient registry data were used for the surgery arm. The 5-year OS rate was 78.2% for SBRT and 74.8% for surgery from both studies. The 5-year PFS rate was 57.0% for SBRT and 63.4% for surgery. The quality of life values of PFS and progressive disease were obtained from domestic and overseas literature (PFS: 0.74, progressive disease: 0.65). The time horizon was set to 10 years. The expected costs and quality-adjusted life years for each treatment group were calculated. All costs are expressed in Japanese yen converted to US dollars (USD). SBRT was the dominant strategy, reducing treatment costs by 4,443.8 USD and increasing quality-adjusted life years by 0.131 compared with surgery. According to probabilistic sensitivity analysis, the probability of SBRT being dominant and cost-effective was 50.6% and 72.4%, respectively. Under the budget impact analysis, the total savings for the patients with stage I NSCLC in Japan was 6,252,870.0 USD (n = 1,407). SBRT is a more cost-effective option than surgery in patients with medically operable stage I NSCLC in Japan. Large-scale epidemiologic studies that reflect the latest clinical realities, such as OS/PFS, will be needed to validate this study's robustness.

Arsenic speciation analysis in human urine for long term epidemiological studies: The Multi-Ethnic Study of Atherosclerosis (MESA)

Arsenic is a ubiquitous toxic metalloid causing serious health problems. Speciation analysis of arsenic in human urine provides valuable insights for large-scale epidemiological studies and informs on sources of exposure as well as human metabolism. The Multi-Ethnic Study of Atherosclerosis (MESA) is a valuable cohort for assessing chronic low-moderate arsenic exposure and health effects in an ethnically diverse US population. We present a state-of-the-art arsenic speciation analysis methodology and its application to 7677 MESA spot urine samples based on high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry. This method is fast, robust and detects a total of 11 individual As species at method detection limits of 0.02–0.03 μg arsenic/L urine for each individual species. Our analytical approach features excellent mean method accuracy (98%) and precision (5%) for the main arsenic species in urine (arsenobetaine, methylarsonic acid, dimethylarsinic acid, and total inorganic As); intra- (3–6%) and inter-day coefficients of variability (5–6%); column recovery (96 ± 7%); and spike recovery (97 ± 6%). The main arsenic species were detectable in ≥95% of urine samples due to the implementation of an oxidation step. Each individual minor arsenic species was detectable in ≤25% of all urines, although at least one of them was detected in almost half the participants. We identified two minor urinary arsenic species as dimethylarsinoylacetic acid and dimethylarsinoylpropionic acid, potential metabolites of seafood-related arsenicals. We observed differences in individual As species excretion by race/ethnicity, with Asian-American participants featuring 3–4 times higher concentrations compared to other participants. We also found differences by site, body mass index, smoking status, rice intake, and water arsenic levels, potentially indicating different exposures or related to individual bio-metabolism. The proposed approach is suitable for epidemiological studies and the collected data will constitute the base for future research on potential health effects of chronic low-level arsenic exposure.