Risk Factor For Disease Research Articles

Correlates of sleep variability in a mobile EEG-based volunteer study

Variable sleep patterns are a risk factor for disease, but the reasons some people express greater within-individual variability of sleep characteristics remains poorly understood. In our study, we leverage BSETS, a novel mobile EEG-based dataset in which 1901 nights in total were recorded from 267 extensively phenotyped participants to identify factors related to demographics, mental health, personality, chronotype and sleep characteristics which predict variability in sleep, including detailed sleep macrostructure metrics. Young age, late chronotype, and napping emerged as robust correlates of increased sleep variability. Correlations with other characteristics (such as student status, personality, mental health and co-sleeping) generally disappeared after controlling for age. We critically examine the utility of controlling the correlates of sleep variability for the means of sleep variables. Our research shows that age and sleep habits affecting the amount of sleep pressure at night are the most important factors underlying sleep variability, with a smaller role of other psychosocial variables. The avoidance of daytime naps emerges as the most promising modifiable behavior associated with increased sleep regularity.

The relationship between contact lens ultraviolet light transmittance and myopia progression: a large-scale retrospective cohort study.

The prevalence of myopia is increasing dramatically around the world, and many studies have suggested the possibility that ultraviolet (UV) light is effective to prevent the onset and progression of myopia. However, UV is a risk factor for diseases that cause refractive errors such as cataract and pterygium. In this study, we evaluated the relationship between UV exposure and myopia progression. The dataset consisted of a total of 337 396 eyes of patients in the 12-to-29-year age range, who were prescribed soft contact lenses (SCL) for refractive error at Okada Eye Clinic in Japan between 2002 and 2011. They were tracked over a five-year period and did not change the type of SCL. In this retrospective cohort study based on medical records, we divided patients into two groups, one prescribed SCL with UV protection (UV-SCL), and another prescribed SCL without UV protection (UV+SCL). Change in refractive power over five years was measured and results compared. It was -0.413 diopter (D) in the UV-SCL group and -0.462 D in the UV+SCL group. Thus, the progression of myopia was slower in the UV-SCL group. The results were also analyzed separately by gender and degree of myopia at the time of initial prescription, which all showed significant differences (P<0.001). Results suggest that UV exposure may advance myopia. Further research is needed to investigate the underlying mechanisms that could explain this.

Healthy aging: A novel therapy to reverse age-related damage

Healthy aging: A novel therapy to reverse age-related damage What if we could turn back the clock on age-associated dysfunctions by using a therapy that not only treats symptoms but acts to correct the underlying pathology and restores cells to normal function? Lori A. Birder and Edwin K. Jackson from the University of Pittsburgh School of Medicine, explain how this could be a possibility. Increases in our aging population will put substantive burdens on the public health system as well as on medical and social services. Though age is a risk factor for disease, it is often overlooked in clinical practice. Many older people suffer from more than one disease, with the likelihood of having two or more conditions rising to 60% by 75 years of age, and both aging and multimorbidity contribute to frailty, which is associated with a risk of other complications. While several pharmacologic or cell-based strategies show promise for slowing the progression of several age-associated disorders, most ‘mask’ symptoms but do not reverse the condition or restore healthy form and function. Despite the prevalence and impact of age-related disorders on quality of life in humans, a multitude of age-related conditions continue to be undertreated simply because there are few successful therapeutic options, especially minimally invasive ones, and no preventative strategies nor known modulating interventions that reverse or delay physiologic changes. To further compound the problem, the prevalence of polypharmacy in the aged population can increase the risk of drug-drug interactions, which may complicate the diagnosis of many age-associated disorders.

9255 Use of Race and Ethnicity in Endocrine Clinical Practice Guidelines

Abstract Disclosure: D. Segura Torres: None. K. Raygoza: None. M. Garcia: None. J.P. Brito: None. M.E. McDonnell: None. M. Corrigan: None. C.R. McCartney: None. R. Dhaliwal: None. N.M. Singh Ospina: None. Clinical practice guidelines (CPG) improve healthcare quality by guiding decision making. Recent trends in CPG development emphasize incorporating race/ethnicity terms and health equity considerations. However, the appropriateness of how race/ethnicity is utilized remains uncertain. Objective This study seeks to evaluate the use of race/ethnicity in published Endocrine Society (ES) CPG and elucidate the context in which race and ethnicity terms are used. Methods: We identified 30 active clinical practice guidelines from ES up to January 2023. Two reviewers independently and in duplicate: a) located statements addressing race/ethnicity using an electronic search with 24 keywords, b) determined the statements' location within guidelines, and c) classified them based on content using frameworks by Cerdena and Gilliam. Disagreements were resolved by consensus. Exclusions were made for statements not addressing race and ethnicity terms in the appropriate context (e.g., “minority” of the panel disagreed), as well as for those in references or duplicates. Results: We reviewed 30 clinical practice guidelines, with 19 of them containing statements related to race or ethnicity. After applying exclusion criteria, we identified a final analytic sample of 114 statements. The majority of these statements were found in the body of the clinical guidelines (79%), followed by the evidence-to-decision framework (14%), and clinical recommendations (7%).The predominant classification were statements in which there was biologization of race/ethnicity 55% (n=63). Discussions on racial/ethnic disparities accounted for 23% (n=26) of the statements, with 31% (n=8) of these including explicit considerations of social context. Additionally, there were descriptions of race-specific treatment or diagnosis/screening in 14% (n=16) and 9% (n=10) of the statements, respectively.Less commonly statements of race/ethnicity reflected the consideration of ancestry as a code for race/ethnicity (n=7, 6%), identified ancestry as a risk factor for disease (n=19, 6%), highlighted racial/ethnic groups as understudied n=6, 5%), normalized findings to the majority group (White centeredness) (n=7, 6%), and other categories (7%). None of the statements employed race/ethnicity terms to emphasize cultural humility or the value of inclusivity in guideline committees. Conclusion: We systematically analyzed how race and ethnicity terms are used in ES CPGs. Our findings align with prior assessments made in non-ES CPG, highlighting the prevalent biologization of race and ethnicity constructs. Addressing this trend and incorporating socio-structural context considerations could bolster the impact of clinical guidelines in promoting health equity. Presentation: 6/1/2024

Brain network fingerprints of Alzheimer's disease risk factors in mouse models with humanized APOE alleles

Alzheimer's disease (AD) presents complex challenges due to its multifactorial nature, poorly understood etiology, and late detection. The mechanisms through which genetic and modifiable risk factors influence disease susceptibility are under intense investigation, with APOE being the major genetic risk factor for late onset AD. Yet the impact of unique risk factors on brain networks is difficult to disentangle, and their interactions remain unclear.To model multiple risk factors, including APOE genotype, age, sex, diet, and immunity we used a cross sectional design, leveraging mice expressing human APOE and NOS2 genes, conferring a reduced immune response compared to mouse Nos2. We used network topological and GraphClass analyses of brain connectomes derived from accelerated diffusion-weighted MRI to assess the global and local impact of risk factors, in the absence of AD pathology.Aging and a high-fat diet impacted extensive networks comprising AD-vulnerable regions, including the temporal association cortex, amygdala, and the periaqueductal gray, involved in stress responses. Sex impacted networks including sexually dimorphic regions (thalamus, insula, hypothalamus) and key memory-processing areas (fimbria, septum). APOE genotypes modulated connectivity in memory, sensory, and motor regions, while diet and immunity both impacted the insula and hypothalamus. Notably, these risk factors converged on a circuit comprising 63 of 54,946 total connections (0.11% of the connectome), highlighting shared vulnerability amongst multiple AD risk factors in regions essential for sensory integration, emotional regulation, decision making, motor coordination, memory, homeostasis, and interoception. APOE genotype specific immune signatures support the design of interventions tailored to risk profiles. Sparse Canonical Correlation Analysis (CCA) including spatial memory as a risk factor resulted in a network comprising 80 edges, showing significant overlap with risk-associated networks from GraphClass. The largest overlaps were observed with networks impacted by diet (47 edges), immunity (39 edges), APOE3 vs 4 (26 edges), sex (23 edges), and age (19 edges), the resulting networks supporting the use of sensory cues in spatial memory retrieval.These network-based biomarkers hold translational value for distinguishing high-risk versus low-risk participants at preclinical AD stages, suggest circuits as potential therapeutic targets, and advance our understanding of network fingerprints associated with AD risk.

Iron accumulation/overload and Alzheimer's disease risk factors in the precuneus region: A comprehensive narrative review.

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by amyloid plaques, neurofibrillary tangles, and neuronal loss. Early cerebral and body iron dysregulation and accumulation interact with AD pathology, particularly in the precuneus, a crucial functional hub in cognitive functions. Quantitative susceptibility mapping (QSM), a novel post-processing approach, provides insights into tissue iron levels and cerebral oxygen metabolism and reveals abnormal iron accumulation early in AD. Increased iron deposition in the precuneus can lead to oxidative stress, neuroinflammation, and accelerated neurodegeneration. Metabolic disorders (diabetes, non-alcoholic fatty liver disease (NAFLD), and obesity), genetic factors, and small vessel pathology contribute to abnormal iron accumulation in the precuneus. Therefore, in line with the growing body of literature in the precuneus region of patients with AD, QSM as a neuroimaging method could serve as a non-invasive biomarker to track disease progression, complement other imaging modalities, and aid in early AD diagnosis and monitoring.

Accurate prediction of disease-risk factors from volumetric medical scans by a deep vision model pre-trained with 2D scans.

The application of machine learning to tasks involving volumetric biomedical imaging is constrained by the limited availability of annotated datasets of three-dimensional (3D) scans for model training. Here we report a deep-learning model pre-trained on 2D scans (for which annotated data are relatively abundant) that accurately predicts disease-risk factors from 3D medical-scan modalities. The model, which we named SLIViT (for 'slice integration by vision transformer'), preprocesses a given volumetric scan into 2D images, extracts their feature map and integrates it into a single prediction. We evaluated the model in eight different learning tasks, including classification and regression for six datasets involving four volumetric imaging modalities (computed tomography, magnetic resonance imaging, optical coherence tomography and ultrasound). SLIViT consistently outperformed domain-specific state-of-the-art models and was typically as accurate as clinical specialists who had spent considerable time manually annotating the analysed scans. Automating diagnosis tasks involving volumetric scans may save valuable clinician hours, reduce data acquisition costs and duration, and help expedite medical research and clinical applications.

Trunk-to-leg volume and appendicular lean mass from a commercial 3-dimensional optical body scanner for disease risk identification

Body shape expressed as the trunk-to-leg volume ratio is associated with diabetes and mortality due to the associations between higher adiposity and lower lean mass with Metabolic Syndrome (MetS) risk. Reduced appendicular muscle mass is associated with malnutrition risk and age-related frailty, and is a risk factor for poor treatment outcomes related to MetS and other clinical conditions (e.g.; cancer). These measures are traditionally assessed by dual-energy X-ray absorptiometry (DXA), which can be difficult to access in clinical settings. The Shape Up! Adults trial (SUA) demonstrated the accuracy and precision of 3-dimensional optical imaging (3DO) for body composition as compared to DXA and other criterion measures. Here we assessed whether trunk-to-leg volume estimates derived from 3DO are associated with MetS risk in a similar way as when measured by DXA. We further explored if estimations of appendicular lean mass (ALM) could be made using 3DO to further improve the accessibility of measuring this important frailty and disease risk factor. SUA recruited participants across sex, age (18-40, 40-60, >60 years), BMI (under, normal, overweight, obese), and race/ethnicity (non-Hispanic [NH] Black, NH White, Hispanic, Asian, Native Hawaiian/Pacific Islander) categories. Each participant had whole-body DXA and 3DO scans, and measures of cardiovascular health. The 3DO measures of trunk and leg volumes were calibrated to DXA to express equivalent trunk-to-leg volume ratios. We expressed each blood measure and overall MetS risk in quartile gradations of trunk-to-leg volume previously defined by National Health and Nutrition Examination Survey (NHANES). Finally, we utilized 3DO measures to estimate DXA ALM using ten-fold cross-validation of the entire dataset. Participants were 502 (273 female) adults, mean age=46.0±16.5y, BMI=27.6±7.1kg/m2 and a mean DXA trunk-to-leg volume ratio of 1.47±0.22 (females: 1.43±0.23; males: 1.52±0.20). After adjustments for age and sex, each standard deviation increase in trunk-to-leg volume by 3DO was associated with a 3.3 (95% odds ratio [OR]=2.4-4.2) times greater risk of MetS, with individuals in the highest quartile of trunk-to-leg at 27.4 (95% CI: 9.0-53.1) times greater risk of MetS compared to the lowest quartile. Risks of elevated blood biomarkers as related to high 3DO trunk-to-leg volume ratios were similar to previously published comparisons using DXA trunk-to-leg volume ratios. Estimated ALM by 3DO was correlated to DXA (r2=0.96, root mean square error=1.5kg) using ten-fold cross-validation. Using thresholds of trunk-to-leg associated with MetS developed on a sample of US-representative adults, trunk-to-leg ratio by 3DO after adjustments for offsets showed significant associations to blood parameters and MetS risk. 3DO scans provide a precise and accurate estimation of ALM across the range of body sizes included in the study sample. The development of these additional measures improves the clinical utility of 3DO for the assessment of MetS risk as well as the identification of low muscle mass associated with poor cardiometabolic and functional health.

An exploratory single-arm open-label clinical study to evaluate the combined effect of Vamana and Sarasvata Churna in reducing excessive daytime sleepiness

BackgroundExcessive Daytime Sleepiness (EDS) is inferred as persistent sleepiness and often a general lack of energy during the day even after apparently adequate or even prolonged nighttime sleep. The subjects may not be identifying excessive daytime sleepiness but may present as feeling tired, lack of energy etc. They may seem apparently healthy and without any other systemic illness. The prevalence was found to be as high as 18 % in 2012 in United Kingdom. Also, it is a risk factor for diseases like Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases. Conventional management (Modafinil, Sodium Oxybate and Stimulants) addresses only the subjective condition in EDS and is associated with adverse effects compromising the quality of life. In the current health scenario there is a need for alternative interventions to manage this disease. On analyzing this condition through Ayurveda, we could understand it as Nidradhikya (Excessive daytime sleepiness) which is caused due to vitiated Kapha Dosha along with Vriddha Tamoguna (increased Tamoguna) that can be managed by Shodhana (biopurification) followed Shamana (pacification) therapies. ObjectiveThis study was aimed to assess the combined effect of Vamana (therapeutic vomiting) and Sarasvata Churna in reducing Excessive Daytime Sleepiness. Materials and methodsThis was a single-arm exploratory open-label clinical trial. 10 subjects having EDS diagnosed using Modified Epworth Sleepiness Scale (MESS) with a score of 10–24 with proper exclusion were recruited from OPD and IPD, Department of Kāyacikitsa, Amrita School of Ayurveda. All the participants were clinically examined, sought for medical history and further checked biochemically to exclude any other systemic illness that may lead to this condition. Only healthy subjects with quality night sleep (assessed by PSQI) and without any other systemic illness were selected. The treatment protocol adopted was Vamana Karma followed by 30 days of Sarasvata Churna as Shamana Aushadha (medicine for pacification). Assessment was done using MESS on 0th day and after 30 days of Shamana Aushadha Sevana. After completion of treatment, the results were statistically analysed using Wilcoxon Signed Rank Test and final conclusion was drawn. ResultsOn analysis of the symptoms using Modified Epworth Sleepiness Scale, the mean total score reduced from 14.8 to 2.8 with 81.08 % relief in these 10 subjects and a significant p value < 0.05 after Vamana followed by 30 days of Shamana Aushadha Sevana. DiscussionVamana helps in Kapha Nirharana (expelling) which removes the Avarana (occlusion) of Manas seen in Nidradhikya. This results in Hrit Shuddhi (purity of heart) that helps in bringing the equilibrium of Mano Gunas (qualities of mind) (Satvoudaryam Tamojayaha) which forms the line of management. Sarasvata Churna which was administered as Shamana Aushadha possesses Medhya (Nootropic), Buddhi Smriti Dhriti Vardhaka (intellect, memory and patience promoting) attributes and is being indicated in Vicetas. Most of the drugs in Sarasvata Churna are Rasayana (rejuvenation) that imparts Indriya Bala (strengthening of senses) and Priti (contempt) to Manas by Prinana (nourishing) of Rasa Dhatu. ConclusionFrom this study, we could conclude that the combination of Vamana Karma followed by Sarasvata Churna administration is effective in reducing EDS.

Abstract P407: Sex and age differences in cardiovascular health in youth referred for hypertension disorders at baseline: A SUPERHERO Registry analysis

Background: The prevalence of hypertension (HTN) and other cardiovascular (CV) disease risk factors (e.g., target organ injury (TOI), obesity, dyslipidemia, hyperglycemia) are increasing steadily in youth. In adults, sex and age differences are established, but remain unknown in children (1–12 years) and adolescents (≥13 years). Objective: Determine sex and age differences in blood pressure (BP) severity, TOI, and CV health in youth referred for HTN disorders. Design/Methods: Cross-sectional analysis of baseline data from the Study of the Epidemiology of Pediatric Hypertension (SUPERHERO), a multisite retrospective Registry of youth referred to subspecialty care for HTN disorders using EHR data. Inclusion criteria were an initial subspecialty clinic visit for HTN disorders identified by ICD-10 codes from 1/1/2016–12/31/2023 and age &lt;19 years. Exclusion criteria were kidney failure on dialysis, kidney transplantation, or pregnancy by ICD-10 codes. The exposures were sex and age at the index visit. Outcomes were BP severity at the index visit based on age, sex, and height-based U.S. guidelines, obesity by BMI or weight-for-length percentiles, and dyslipidemia, hyperglycemia, and TOI (heart and kidney-specific) by ICD-10 codes. We estimated the associations with unadjusted generalized linear models; our directed acyclic graphs did not identify any open, biasing paths necessitating adjustment for confounding factors . Results: Of the 9,356 participants, mean age ± SD was 12.8 ±4.5 years, 36% (n=3,372) were female, 56% (n=5,261) were adolescents, 23% (n=2,162) had stage 2 HTN, 5% (n=451) had TOI (2% heart, 3% kidney), 60% (n=5,655) had obesity, 9% (n=834) had dyslipidemia, and 10% (n=944) had hyperglycemia. Despite less BP severity, females had a higher risk of kidney TOI (RR 1.49, CI: 1.19 to 1.86), hyperglycemia (RR 1.48, CI: 1.3 to 1.68), and number of CV health risk factors (RR 1.1, CI:1.01 to 1.19). Compared to children, adolescents were more likely to have worse BP severity (RR 1.7, CI: 1.6 to 1.8) and HTN (RR 1.1, CI:1.1 to 1.2), and less risk for dyslipidemia (RR: 0.8, 0.7 to 0.9) Conclusions: In a large multisite cohort of youth referred for HTN disorders, females had a 49% higher risk of TOI and 48% greater risk for hyperglycemia despite lower BP severity. Adolescents had more severe BP and HTN compared to children. Next steps in this study include investigating age and sex differences in ambulatory BP and laboratory and echocardiogram data.

Common molecular and pathophysiological underpinnings of delirium and Alzheimer’s disease: molecular signatures and therapeutic indications

BackgroundDelirium and Alzheimer's disease (AD) are common causes of cognitive dysfunction among older adults. These neurodegenerative diseases share a common and complex relationship, and can occur individually or concurrently, increasing the chance of permanent mental dysfunction. However, the common molecular pathophysiology, key proteomic biomarkers, and functional pathways are largely unknown, whereby delirium is superimposed on AD and dementia.MethodsWe employed an integrated bioinformatics and system biology analysis approach to decipher such common key proteomic signatures, pathophysiological links between delirium and AD by analyzing the gene expression data of AD-affected human brain samples and comparing them with delirium-associated proteins. The present study identified the common drug target hub-proteins examining the protein–protein interaction (PPI) and gene regulatory network analysis. The functional enrichment and pathway analysis was conducted to reveal the common pathophysiological relationship. Finally, the molecular docking and dynamic simulation was used to computationally identify and validate the potential drug target and repurposable drugs for delirium and AD.ResultsWe detected 99 shared differentially expressed genes (sDEGs) associated with AD and delirium. The sDEGs-set enrichment analysis detected the transmission across chemical synapses, neurodegeneration pathways, neuroinflammation and glutamatergic signaling pathway, oxidative stress, and BDNF signaling pathway as the most significant signaling pathways shared by delirium and AD. The disease-sDEGs interaction analysis highlighted the other disease risk factors with delirium and AD development and progression. Among the sDEGs of delirium and AD, the top 10 hub-proteins including ALB, APP, BDNF, CREB1, DLG4, GAD1, GAD2, GFAP, GRIN2B and GRIN2A were found by the PPI network analysis. Based on the maximum molecular docking binding affinities and molecular dynamic simulation (100 ns) results, the ALB and GAD2 were found as prominent drug target proteins when tacrine and donepezil were identified as potential drug candidates for delirium and AD.ConclusionThe study outlined the common key biomolecules and biological pathways shared by delirium and AD. The computationally reported potential drug molecules need a deeper investigation including clinical trials to validate their effectiveness. The outcomes from this study will help to understand the typical pathophysiological relationship between delirium and AD and flag future therapeutic development research for delirium.

Design and Psychometrics of the Awareness and Self-Care Performance Questionnaire of Diabetic Patients in the Coronavirus Disease 2019 Pandemic

Background: The sudden emergence of the coronavirus disease 2019 (COVID-19) epidemic worldwide has led to numerous problems for patients with chronic diseases, such as diabetics, due to the lack of required information to deal with the disease. The present research aims to investigate the design and psychometrics of the Awareness and Self-Care Performance Questionnaire of diabetic patients during the COVID-19 pandemic. Methods: The present methodological study aimed to investigate the design and psychometrics of the Awareness and Self-Care Performance Questionnaire. The face and content validity were assessed through both quantitative and qualitative studies. For the quantitative study, 100 diabetic patients were randomly selected during the COVID-19 pandemic. The reliability of the questionnaire was assessed using the internal consistency method by Cronbach’s alpha coefficient. Results: The original version of the questionnaire was designed with 82 items and the final version with 56 items (awareness [32 items] and self-care performance [24 items]) with seven areas, including disease characteristics, prevention ways, ways of disease transmission, disease symptoms, disease risk factors, diet, and care methods. The content validity index (CVI) was 0.97, the content validity ratio (CVR) was 0.93, and the internal consistency of the questionnaire was calculated to be 0.80 using Cronbach’s alpha coefficient, showing the appropriate validity and reliability of this questionnaire. Conclusion: The Awareness and Self-Care Performance Questionnaire of diabetic patients in the COVID-19 pandemic possesses the required validity and reliability to evaluate the knowledge level of diabetic patients in infectious pandemics, such as COVID-19, and it has the applicability to be used in similar conditions. It is suggested that the questionnaire’s construct validity be measured to enhance the content validity.

Effects of transcranial direct current stimulation on cognition in MCI with Alzheimer's disease risk factors using Bayesian analysis

Despite the growing interest in precision medicine-based therapies for Alzheimer's disease (AD), little research has been conducted on how individual AD risk factors influence changes in cognitive function following transcranial direct current stimulation (tDCS). This study evaluates the cognitive effects of sequential tDCS on 63 mild cognitive impairment (MCI) patients, considering AD risk factors such as amyloid-beta deposition, APOE ε4, BDNF polymorphism, and sex. Using both frequentist and Bayesian methods, we assessed the interaction of tDCS with these risk factors on cognitive performance. Notably, we found that amyloid-beta deposition significantly interacted with tDCS in improving executive function, specifically Stroop Word-Color scores, with strong Bayesian support for this finding. Memory enhancements were differentially influenced by BDNF Met carrier status. However, sex and APOE ε4 status did not show significant effects. Our results highlight the importance of individual AD risk factors in modulating cognitive outcomes from tDCS, suggesting that precision medicine may offer more effective tDCS treatments tailored to individual risk profiles in early AD stages.

Risk for progression to type 1 diabetes in first-degree relatives under 50 years of age.

The detection of pancreatic autoantibodies in first-degree relatives of patients with type 1 diabetes (T1D) is considered a risk factor for disease. Novel available immunotherapies to delay T1D progression highlight the importance of identifying individuals at risk who might benefit from emerging treatments. The objective was to assess the autoimmunity in first-degree relatives of patients with T1D, estimate the time from autoimmunity detection to the onset of clinical diabetes, and identify the associated risk factors. Retrospective multicenter study of 3,015 first-degree relatives of patients with T1D recruited between 1992 and 2018. Pancreatic autoantibodies (IAA, GADA, IA2A, and ZnT8A) were determined by radioimmunoassay, starting the analyses at diagnosis of the proband. All those with positive autoimmunity and normal fasting blood glucose without clinical symptoms of diabetes were followed up in the study. The progression rate to T1D was assessed according to sex, relationship with the proband, age at autoimmunity detection, type/number of autoantibodies, and HLA-DRB1 genotype. Cox proportional-hazard models and Kaplan-Meier survival plots were used for statistical analyses. Among the relatives, 21 progenitors [43.7 years (IQR: 38.1-47.7)] and 27 siblings [7.6 years (IQR: 5.8-16.1)] had positive autoantibodies. Of these, 54.2% (95% CI: 39.2%-68.6%) developed T1D (age at autoimmunity detection 11 months to 39 years) in a median of 5 years (IQR: 3.6-8.7; ranged from 0.9 to 22.6 years). Risk factors associated with faster progression to T1D were multiple autoimmunity and <20 years at autoimmunity detection. Younger relatives (<20 years) with multiple autoantibodies had a 5-year cumulative risk of developing diabetes of 52.9% (95% CI: 22.1%-71.6%) and a 20-year risk of 91.2% (95% CI: 50.5%-98.4%). The 20-year risk decreased to 59.9% (95% CI: 21.9%-79.5%) if only one risk factor was met and to 35.7% (95% CI: 0.0%-66.2%) if the relative was older than 20 years with one autoantibody. In first-degree relatives with autoimmunity, the time to progression to T1D is faster in children and adolescents with multiple autoantibodies. Young adults are also at risk, which supports their consideration in screening strategies for people at risk of developing T1D.

Genome wide association study of clinical duration and age at onset of sporadic CJD.

Human prion diseases are rare, transmissible and often rapidly progressive dementias. The most common type, sporadic Creutzfeldt-Jakob disease (sCJD), is highly variable in clinical duration and age at onset. Genetic determinants of late onset or slower progression might suggest new targets for research and therapeutics. We assembled and array genotyped sCJD cases diagnosed in life or at autopsy. Clinical duration (median:4, interquartile range (IQR):2.5-9 (months)) was available in 3,773 and age at onset (median:67, IQR:61-73 (years)) in 3,767 cases. Phenotypes were successfully transformed to approximate normal distributions allowing genome-wide analysis without statistical inflation. 53 SNPs achieved genome-wide significance for the clinical duration phenotype; all of which were located at chromosome 20 (top SNP rs1799990, pvalue = 3.45x10-36, beta = 0.34 for an additive model; rs1799990, pvalue = 9.92x10-67, beta = 0.84 for a heterozygous model). Fine mapping, conditional and expression analysis suggests that the well-known non-synonymous variant at codon 129 is the obvious outstanding genome-wide determinant of clinical duration. Pathway analysis and suggestive loci are described. No genome-wide significant SNP determinants of age at onset were found, but the HS6ST3 gene was significant (pvalue = 1.93 x 10-6) in a gene-based test. We found no evidence of genome-wide genetic correlation between case-control (disease risk factors) and case-only (determinants of phenotypes) studies. Relative to other common genetic variants, PRNP codon 129 is by far the outstanding modifier of CJD survival suggesting only modest or rare variant effects at other genetic loci.

Effect Of Coffee Drinking Habit to Blood Pressure and Hemoglobin Levels on Women of Childbearing Age

Background: Tenggerese people, especially women, have a habit of drinking coffee, and it has become a daily habit. Coffee is often associated with risk factors for diseases in the community such as anemia and hypertension. This study aims to determine the effect of coffee drinking quantity (1-2 cups, 3-4 cups, and ≥ 5 cups of coffee per day) on hemoglobin levels and blood pressure. Subjects and Method: A quantitative study with a cross-sectional study design was done. This study population was women of reproductive age (15 to 49 years) in Ngadipuro Hamlet, Tengger, East Java, Indonesia. The independent variable of this study is the of daily coffee drinking per cup and the dependent variable of this study is the hemoglobin levels in women of childbearing age. The study instrument used was a questionnaire to screen for those who were a daily coffee drinker and a blood hemoglobin rapid test kit was used to measure the level of hemoglobin.The number of samples in this study was 193 respondents which was chosen using the random sampling technique. Analysis of the quantity of coffee drinking on hemoglobin levels by the Annova test while on blood pressure by the Kruskal Wallis test through SPSS software. Results: The result showed that the quantity of coffee per day on hemoglobin levels had a significance p&lt;0.001. While the quantity of coffee per day on blood pressure had a significance p=0.361. Conclusion: It can be concluded that drinking 1-2 cups of coffee, 3-4 cups, and ≥ 5 cups of coffee daily simultaneously affects hemoglobin levels. In this case, the more quantity of coffee per day, the lower the hemoglobin level. However, the quantity of coffee had no significant effect on blood pressure.

Factors Predictive of Non-Alcoholic Fatty Liver Disease in Non-Obese Pakistani Population

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of chronic liver disease worldwide, with a rising incidence in developing countries. In Pakistan, the estimated prevalence ranges from 14-47%. Studies have shown that NAFLD is also not uncommon among the non-obese lean population. Objective: The aim of this study was to evaluate the factors predictive of non-alcoholic fatty liver disease in a non-obese Pakistani population, defined by a body mass index (BMI) of less than 23 kg/m². Methods: This cross-sectional study was conducted at the Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation from November 1, 2020, to October 31, 2021. A total of 194 patients with BMI &lt; 23 kg/m² presenting with abdominal pain were included. Exclusion criteria were viral hepatitis, significant alcohol intake, hepatocellular carcinoma, or other malignancies. Data collection involved recording demographic information, medical history, and clinical parameters. Ultrasound abdomen examinations were performed after 8-10 hours of fasting to diagnose NAFLD. Clinical assessments included history of hypertension and smoking, and laboratory tests such as liver function tests, fasting blood sugar levels, and lipid profiles. The primary outcome was the presence of fatty liver on ultrasound. Statistical analysis was conducted using SPSS version 25.0. Continuous variables were analyzed using the Student t-test and categorical variables using the Chi-square test. Significant variables in univariate analysis underwent multivariate logistic regression to identify independent predictors of lean NAFLD. A p-value ≤ 0.05 was considered significant. Results: Out of the 194 patients, 107 (55.2%) were females. The mean age was 36.1 ± 9.6 years, and the mean BMI was 21 ± 1.7 kg/m². NAFLD was detected in 48 (24.7%) patients. Among the study population, 78 (40.2%) were hypertensive, 40 (20.6%) were diabetic, 49 (25.3%) were smokers, and 54 (27.8%) had increased triglyceride levels. Decreased HDL-C levels were observed in 72 (37.1%) patients. Univariate analysis identified hypertension (p ≤ 0.001), diabetes (p ≤ 0.001), smoking (p ≤ 0.001), hypertriglyceridemia (p ≤ 0.001), and decreased HDL-C levels (p ≤ 0.001) as significant factors. Multivariate logistic regression showed that diabetes (OR: 9.4, p = 0.037), smoking (OR: 46.4, p ≤ 0.001), hypertriglyceridemia (OR: 4.75, p = 0.016), and decreased HDL-C levels (OR: 36.8, p ≤ 0.001) were independently associated with lean NAFLD. Conclusion: Non-obese individuals with a BMI less than 23 kg/m² can develop NAFLD and related complications. The study identified diabetes, smoking, hypertriglyceridemia, and decreased HDL-C levels as significant predictors of lean NAFLD. Further studies are needed to enhance the understanding of the disease's risk factors and behavior in this population.

Melanoma immunotherapy longitudinal database: A comprehensive approach to capture oncological and toxicity data.

e23314 Background: Evaluating immunotherapy approaches is consistently performed in melanoma, a forefront cancer in immunotherapy responsiveness. Although immune checkpoint inhibitors (ICIs) showed the highest significant survival benefits in melanoma, 50% of patients experience recurrence/refractory disease, and ~59% develop grade 3/4 immune-related adverse events (irAEs). Thus, understanding the disease's natural history, exploring biomarkers of response/toxicity, and identifying the efficacy/safety of immunotherapy using real-world data is warranted. Methods: We established a centralized pro-/retrospective database on Research Electronic Data Capture (REDCap), encompassing patients' demographics/comorbidities, disease risk factors, clinicopathological parameters, genomic/immune profiling, treatment modalities, tumor outcomes, irAEs, and patients’ reported outcomes (PROs). Additionally, to streamline data collection and minimize the required time, effort, and cost for manual retrieval, we developed an automated pathway for data capture using MD Anderson Cancer Center (MDACC) electronic data capture (EDC) tools which pull clinical data from EPIC. Data quality will be validated by comparing it to manually retrieved data from an ongoing study of melanoma patients treated with ICIs in the adjuvant setting (NCT04990726). Results: A total of 4074 immunotherapy-treated melanoma patients were identified. We automatically captured demographics and laboratory values at predefined time points from REDCap, along with PROs using validated electronic self-reported questionnaires already built in REDCap. We also automatically captured family history, comorbidities, pathology data, and cancer treatments from the Data Management Initiative (DMI) validated software that automatically captures data from 12 various institutional sources that complement each other, including Radiation Oncology Database, the Biospecimen Information Management System,...etc. Moreover, genomic data were automatically pulled from the Molecular and Clinical Data Integration Platform for 1850 patients. Automated capture of tumor response and irAEs according to the Response Evaluation Criteria in Solid Tumors 1.1. and Common Terminology Criteria for Adverse Events version-5, respectively are currently ongoing and will be presented. Conclusions: Integrating EDC tools demonstrated accurate real-time data capture and minimized the manual retrieval burden. Our immunotherapy-treated melanoma patients’ cohort provides a comprehensive and a valuable resource for exploring the safety signals and efficacy of various immunotherapeutic approaches beyond clinical trials.

Care for the cerebrovascular accident survivors: experiences of family caregivers

BackgroundThe role of family caregivers in the management of cerebrovascular accident survivors is invaluable. So far, there is a strong evidence affirming the effectiveness of family support for cerebrovascular accident survivors. Meanwhile, caring for cerebrovascular survivors can be labour and time intensive and pretty stressful for caregivers. The purpose of the study was to examine the lived experiences of family caregivers of cerebrovascular accident survivors in the Ho Municipality in the Volta Region of Ghana. This aims are to establish their caregivers’ knowledge, preparedness, and impact of caregiving on the caregiver, and coping strategies caregivers adopted.MethodsUsing a four-item (with 14 prompts) interview guide and descriptive phenomenological approach, we gathered and analysed data from 37 family caregivers in the Ho Municipality of Ghana.ResultsWe found that caregivers had limited knowledge about cerebrovascular disease-risk factors and were ill-prepared for their caregiving roles. Additionally, we found limited knowledge about coping strategies among the caregivers. We further report that some caregivers lost close relationships, and their jobs because of the caregiving, they also used fasting and prayer as coping strategies.ConclusionsCaregivers suffered broken relationship, loss their jobs and incomes due to their caregiving roles. Moreover, some engaged in fasting and prayers, and alcohol use to cope with the stress associated with caring for the cerebrovascular accident survivors. We discussed the potential implications of our findings on the realisation of the Sustainable Development Goal 3.4. The aim of this goal is to reduce by 75% premature deaths due to cerebrovascular and other non-communicable diseases by 2030.

Assessment of vitamin D status and associated risk factors in high-altitude populations affected by multiple sclerosis: A case-control study.

Several studies have suggested a correlation between serum vitamin D (VitD) level and multiple sclerosis (MS). MS has a known latitudinal distribution pattern, with greater incidence, prevalence, and mortality rates at higher latitudes. This study aims to assess levels of VitD and serum potassium in subjects with MS and the impact of gender and age as disease risk factors. A cross-sectional case-control study was conducted in a high-altitude region of Saudi Arabia. VitD deficiency was defined as serum 25 (OH)D level of ≤20 ng/mL and insufficiency as a serum level between >20 ng/mL and <30 ng/mL. Two hundred patients with MS volunteered for the study, and 160 healthy participants served as controls. VitD and serum potassium were measured in patients and controls. Student t test and regression analysis were used to analyze the data. The average MS patient age was 37.37 ± 10.8 years. Most (73.02%) MS patients suffered from deficient vitamin D, while insufficiency (20-29 ng/mL) was found in 12.17%. Only 6.35% had sufficient vitamin D (30-40 ng/mL). VitD was significantly decreased in MS patients compared to the healthy controls (17.036 vs 25.01 ng/mL, P < .001), while serum potassium was also decreased (4.278 vs 4.329 mmol/L, P = .269). Risk factors found to have a statistically significant association with MS included female gender (odd ratio [OR] = 1.72, 95% confidence interval: 1.016-2.915; P = .044) and patient age < 40 years (OR = 1.04, 95% confidence interval: 1.023-1.054; P = .044). VitD was significantly lower in MS patients. The prevalence of MS was higher among women and younger individuals in a high-altitude population in Saudi Arabia.