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Background: To prospectively examine the association between physical fitness and risk of disability retirement in a large population-based cohort. Methods: This study utilized data from Health 2011 survey Physical Activity subsample (n = 4898), combined with information on disability retirement derived from 2 national registers. In total, 2455 individuals aged 18–74 years underwent the physical fitness test protocol concerning measures of cardiorespiratory fitness, muscle strength, and balance. The outcome variable was disability retirement, during the follow-up period of 9 years. After excluding those not at risk of disability retirement (ie, age ≥63 y) or who had already been granted disability pension, and those who had not completed the fitness protocol, the analytical sample included 1381 participants. Data were analyzed using Cox regression model with SPSS (version 29). Results: During the 9-year follow-up period, 61 individuals (4.4%) transitioned to a disability retirement. Cox regression analysis showed an association between the various physical fitness subdomains and the risk of disability retirement. In model 1, all fitness tests were associated with the risk of disability retirement, except the one-leg stand test with hazard ratios ranging from 1.69 (95% CI, 0.86–3.34) to 5.75 (95% CI, 1.84–17.90). Further adjustment for sociodemographic, health behavior, and health-related covariates attenuated the associations and statistical significance was lost, except for the vertical jump test (hazard ratio = 4.33; 95% CI, 1.32–14.10) and 6-minute walk test (hazard ratio = 3.81; 95% CI, 1.35–10.70). Conclusion: These findings highlight the importance of physical fitness for preventing work disability. [ABSTRACT FROM AUTHOR]

BACKGROUND: Interpersonal violence is a leading cause of morbidity, with potentially severe adverse consequences for the mental health of the injured persons. The extent to which violent injury is associated with subsequent suicidal behavior, however, remains unclear. This study aimed to examine how violent injury was associated with subsequent deliberate self-harm and death by suicide. METHODS: This retrospective cohort study used nationwide longitudinal registry data from Norway to identify all individuals presenting to emergency services in 2010-2018 with a violence-related injury, along with sex- and age-matched control individuals from the general population. The primary outcomes were any emergency visit for deliberate self-harm (DSH) and suicide death, observed through 31 December 2018. Rates of each outcome were compared between violence-injured patients and comparison individuals using stratified multivariable Cox regression models, controlling for sociodemographic characteristics as well as history of psychiatric treatment and DSH. Secondary analyses tested for moderation by sex, age, and prior psychiatric treatment. FINDINGS: Violence-injured patients (n = 28,276) had substantially higher rates of DSH (946.7 per 100,000 person-years) and suicide death (74.5 per 100,000) when compared to controls (n = 282,760; 90.0 and 15.2 per 100,000, respectively). The hazard ratios (HRs) remained significantly higher even after accounting for covariates (HRadj for DSH: 5.11; 95% CI: 4.62, 5.66; HRadj for suicide: 2.40; 95% CI: 1.78, 3.24). Sex differences in this association were negligible, but the association between violence injury and DSH increased with age. Violence-injured patients with prior psychiatric treatment had the highest risk of suicidal behavior. INTERPRETATION: Violence-injured patients experience significantly excess rates of suicidal behavior, a finding with potential to inform both clinical intervention and population-level suicide prevention strategies. FUNDING: Fulbright Norway Scholarship.

Purpose: Artificial intelligence can predict the age of an individual using color fundus photographs (CFPs). This study aimed to investigate the accuracy of age prediction in the Kumejima study using fundus parameters and to clarify age-related changes in the fundus. Methods: We used nonmydriatic CFPs obtained from the Kumejima population study, including 1,646 right eyes of healthy participants with reliable fundus parameter measurements. The tessellation fundus index was calculated as R/(R + G + B) using the mean value of the red–green–blue intensity in eight locations around the optic disc and foveal region. The optic disc ovality ratio, papillomacular angle, and retinal vessel angle were quantified as previously described. Least absolute shrinkage and selection operator regression with leave-one-out cross-validation was used to predict age. The relationship between the actual and predicted ages was investigated using Pearson's correlation coefficient. Results: The mean age of included participants (834 males and 812 females) was 53.4 ± 10.1 years. The mean predicted age based on fundus parameters was 53.4 ± 8.9 years, with a mean absolute error of 3.64 years, and the correlation coefficient between actual and predicted age was 0.88 (p < 0.001). Older patients had greater red and green intensities and weaker blue intensities in the peripapillary area (p < 0.001). Conclusions: Age could be predicted using the CFP parameters, and there were notable age-related changes in the peripapillary color intensity. The age-related changes in the fundus may aid the understanding of the mechanism of fundus diseases such as age-related macular degeneration. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have established a history of shoulder dystocia as an important risk factor for shoulder dystocia, but studies on shoulder dystocia by severity are scarce. It is unknown if shoulder dystocia tends to be passed on between generations. We aimed to assess the recurrence risk of shoulder dystocia by severity in the same woman and between generations on both the maternal and paternal side. We also assessed the likelihood of a second delivery and planned cesarean section after shoulder dystocia. Material and methods: This was a population‐based cohort study, using data from the Medical Birth Registry of Norway. To study recurrence in the same mother, we identified 1 091 067 pairs of first and second, second and third, and third and fourth births in the same mother. To study intergenerational recurrence, we identified an individual both as a newborn and as a mother or father in 824 323 mother‐offspring pairs and 614 663 father‐offspring pairs. We used Bayesian log‐binomial multilevel regression to calculate relative risks (RR) with 95% credible intervals. Results: In subsequent deliveries in the same woman the unadjusted RR of recurrence was 7.05 (95% credible interval 6.39–7.79) and 2.99 (2.71–3.31) after adjusting for possible confounders, including current birthweight. The RRs were higher with severe shoulder dystocia as exposure or outcome. With severe shoulder dystocia as both exposure and outcome, unadjusted and adjusted RR was 20.42 (14.25–29.26) and 6.29 (4.41–8.99), respectively. Women with severe and mild shoulder dystocia and those without had subsequent delivery rates of 71.1, 68.9 and 69.0%, respectively. However, the rates of planned cesarean section in subsequent deliveries for those without shoulder dystocia, mild and severe were 1.3, 5.2 and 16.0%, respectively. On the maternal side the unadjusted inter‐generational RR of recurrence was 2.82 (2.25–3.54) and 1.41 (1.05–1.90) on the paternal side. Corresponding adjusted RRs were 1.90 (1.51–2.40) and 1.19 (0.88–1.61), respectively. Conclusions: We found a strong recurrence risk of shoulder dystocia, especially severe, in subsequent deliveries in the same woman. The inter‐generational recurrence risk was higher on the maternal than paternal side. Women with a history of shoulder dystocia had more often planned cesarean section. [ABSTRACT FROM AUTHOR]

Aim: This paper aimed to answer how psychometric methods based on neurotypical populations can serve as valid instruments in the assessment and diagnosis of intellectual disability in individuals with atypical development. The genetic, structural, and functional features of CHARGE make it uniquely suited to address this question. Method: A Norwegian population of individuals with CHARGE (N = 35) underwent assessment procedures according to DSM-5 guidelines for the evaluation of an intellectual disability diagnosis. Results from cognitive testing (Wechsler Intelligence Scales) and parental evaluation of adaptive skills (Vineland Adaptive Behavioral Scale) were obtained and compared to their respective norm samples to explore any methodological inconsistencies. Result: Significant differences emerged between the participants and the norm samples. Global cognition obtained from Wechsler revealed a bimodal distribution, suggesting a two-group sample, with the youngest children forming their own subgroup. Comparisons of the different age-groups' performances demonstrated the lowest results among the preschoolers while the adults scored the highest. The global adaptive behavior score turned out significantly lower than the performance-based scores, thereby deflating the overall estimate of global intellectual abilities. Conclusion: For individuals with CHARGE, the effect of the atypicality seemed most apparent during early childhood, stabilizing and subsiding towards adulthood. The test results' interpretability was weakest for the preschoolers progressively increasing until peaking in adulthood, emphasizing the importance of delaying the assessment and diagnosis of intellectual disability. Because of several validity issues connected to the observation-based measure, complementary testing should precede clinical evaluations when possible in the diagnostics of individuals with CHARGE. [ABSTRACT FROM AUTHOR]

Aim: To evaluate associations between social disadvantage and insulin pump use among adults with type 1 diabetes (T1D) in the context of a universal publicly funded insulin pump programme in Ontario, Canada, and to ascertain whether social disparities in insulin pump programme enrolment have decreased over time. Methods: Population‐based cross‐sectional studies were conducted using administrative healthcare data in Ontario, Canada. First, among adults aged older than 18 years diagnosed with T1D before 31 March 2021, logistic regression was used to assess the association between neighbourhood social disadvantage (Ontario marginalization index quintiles) and insulin pump use. Second, among all paediatric and adult applicants to the insulin pump programme from 1 September 2006 to 31 March 2022, ordinal logistic regression was used to evaluate associations between year of insulin pump initiation and social disadvantage. Results: Among 27 453 adults with T1D, 60% used insulin pumps. Greater social disadvantage was associated with lower odds of insulin pump use (adjusted odds ratio [OR] 0.44 [95% confidence interval {CI} 0.39‐0.48] for greatest vs. lowest social disadvantage quintile). Among 21 002 paediatric and adult applicants to the insulin pump programme, social disparities in pump use decreased in the first 3 years of the programme, plateaued until 2020, then increased from 2020 to 2022, with no change in the odds of being in a higher social deprivation quintile for 2022 relative to 2007 (OR 1.09 [95% CI 0.83‐1.44]). Conclusions: Despite a universal pump programme for individuals with T1D, disparities by social disadvantage persist. Residual financial and non‐financial barriers must be addressed to promote equitable insulin pump uptake. [ABSTRACT FROM AUTHOR]

This research aimed to systematically uncover the metastatic characteristics and survival rates of lung cancer subtypes and to evaluate the impact of surgery at the primary tumor site on cancer-specific survival in DM lung cancer. We used the Surveillance, Epidemiology, and End Results (SEER) database (2010–2019) to identify primary lung cancers with DM at presentation (M1). Kaplan–Meier (KM) survival curves were generated and compared utilizing log-rank tests. Cox regression methods were employed to determine hazard ratios (HR) and 95% confidence intervals related to CSS factors. Inverse probability of treatment weighting (IPTW) was applied to reduce bias. We analyzed 77,827 M1 lung cancer cases, with 41.22% having DM at presentation. Bone metastasis was most common in ADC, ASC, SCC, LCC; brain in LCNEC; liver in SCLC. Lung was common in TC + AC and SCC. Long-term survival was best in TC + AC and worst in SCLC (p < 0.001). Male gender, age < 50, primary tumor site (main bronchus, lower lobe), large tumor diameter, ADC/SCLC/SCC pathology, and regional lymph node involvement were significant risk factors for multiorgan metastasis. Age ≥ 50, male, large tumor diameter, positive lymph nodes, and multiorgan metastases were associated with lower CSS. In contrast, radiotherapy, chemotherapy, systemic therapy, and surgery were associated with higher CSS rates. Primary tumor resection improved survival in lung cancer patients (excluding small cell lung cancer, SCLC) with single organ metastases (KM log rank p < 0.001, HR = 0.6165; 95% CI (0.5468–0.6951)), especially in brain (p < 0.001, HR = 0.6467; 95% CI (0.5505–0.7596)) and bone (p = 0.182, HR = 0.6289; p < 0.01), but not in liver or intrapulmonary metastases after IPTW. Significant differences in DM patterns and corresponding survival rates exist among lung cancer subtypes. Primary tumor resection improves survival in lung cancer patients (excluding small cell lung cancer, SCLC) with single organ metastases, with better outcomes in patients with brain and bone metastases, while no significant benefit was seen in patients with liver and intrapulmonary metastases. [ABSTRACT FROM AUTHOR]

Background: Education has been shown to be positively associated with cognitive performance. However, the pathways via lifestyle-related disease through which education is related to cognitive performance have not been sufficiently explored. Diabetes is an important lifestyle-related disease with increasing prevalence worldwide. Low education is associated with an increased risk of developing diabetes, while diabetes may also lead to a deterioration in cognitive performance. This study aims to explore if the associations between education and cognitive function is mediated by the diabetes status among older adults. Methods: The data utilized in this study were derived from the first two waves of the Dutch Lifelines Cohort Study (2006–2015). The analyzed sample included 26,131 individuals aged 50 years or above at baseline. The baseline assessment included measurements of educational attainment (exposure) and the potential mediator diabetes. The outcome of cognitive function was assessed using age-standardized reaction times from the psychomotor function and attention tasks, as measured by the Cogstate Brief Battery. The Cogstate Brief Battery was only conducted at the follow-up assessment, not at the baseline assessment. Faster reaction times correspond to higher cognitive performance. The study employed linear and logistic regression models, in addition to a causal mediation approach which estimated the average causal mediation effect (ACME). Results: Higher education was associated with a lower risk of diabetes (b= -0.1976, 95%CI= -0.3354; -0.0597) compared to low or middle education as well as with faster reaction times (b= -0.2023, 95%CI= -0.2246; -0.1798), implying better cognitive function. Diabetes was associated with slower reaction times (b = 0.0617, 95%CI = 0.0162; 0.1072). Most importantly, the mediation approach identified a significant indirect effect of education on cognitive function via the diabetes status (ACME= -0.00061, 95%CI= -0.00142; -0.00011). Discussion: The findings emphasize the potentially importance of diabetes in explaining the role of education in promoting healthy cognitive function and mitigating the risk of cognitive decline. Early detection and treatment of diabetes may be particularly beneficial for individuals with low or middle levels of education in order to maintain good levels of cognitive function. [ABSTRACT FROM AUTHOR]

Introduction: Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly becoming a prevalent cause of hepatocellular carcinoma (HCC). Our study examines the burden of MASH-related HCC globally, regionally, and nationally, along with associated risk factors from 1990 to 2019, considering variables such as age, sex, and socioeconomic status. Objective: We aimed to report the global, regional, and national burden of liver cancer due to MASH and its attributable risk factors between 1990 and 2019, by age, sex, and sociodemographic index (SDI). Methods: Utilizing the Global Burden of Disease 2019 project, we analyzed data on prevalence, mortality, and disability-adjusted life years (DALYs) for liver cancer attributable to MASH across 204 countries. We provided counts and rates per 100,000 population, including 95% uncertainty intervals. Results: In 2019, there were 46.8 thousand cases of MASH-related HCC, leading to 34.7 thousand deaths, and 795.8 thousand DALYs globally. While the prevalence increased by 19.8% since 1990, the death and DALY rates decreased by 5.3% and 15.1%, respectively. The highest prevalence was in High-income Asia Pacific, with the greatest increases observed in Australasia, Central Asia, and High-income North America. Southern Sub-Saharan Africa reported the highest death rate, while the lowest rates were in parts of Latin America, Central Sub-Saharan Africa, and Eastern Europe. DALY rates were the highest in Southern Sub-Saharan Africa and the lowest in Tropical Latin America. Discussion: The burden of MASH-related HCC is expected to rise slightly over the next decade. This disease, which is not associated with the SDI, remains a major public health problem. In addition, the escalating rates of obesity, demographic shifts, and an aging population could position MASH as a leading factor in liver cancer cases, surpassing viral hepatitis. It is imperative, therefore, that the forthcoming years see the implementation of strategic interventions aimed at the early detection and prevention of liver cancer associated with MASH. [ABSTRACT FROM AUTHOR]

Background and Objectives: While the connection between decreased kidney function and diabetes mellitus (DM) is commonly acknowledged, there is insufficient research examining the relationship between higher-than-normal estimated glomerular filtration rate (eGFR) and the incidence risk of new-onset DM. Our research aimed to explore the relationship between an eGFR and the incidence risk of new-onset DM in the Korean general population through a nationwide longitudinal study. Methods: This research employed the cohort records of the National Health Insurance Service in Korea, analyzing records from 2,294,358 individuals between the ages of 20 and 79 who underwent health check-ups between 2010 and 2011. The eGFR levels from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation were used to assess the renal function. New-onset DM was defined as two or more claims with the International Classification of Diseases-10 classification codes E10 to E14, being prescribed any medication for lowering blood glucose, or having a record of fasting plasma glucose levels of ≥126 mg/dL from a health examination after the index date. Results: The mean age of subjects was 47.34 ± 13.76 years. The 150,813 (6.57%) new-onset DM cases were identified over a median follow-up of 9.63 years. In the multivariable Cox regression analysis, in comparison with the 5th decile, the 10th (≥114.12 mL/min/1.73 m2) (hazard ratio (HR): 0.52, 95% confidence interval (CI) (0.50–0.54), p < 0.001) eGFR decile was significantly associated with a decreased incidence of new-onset DM. Moreover, eGFR >120 mL/min/1.73 m2 was associated with a reduced risk of new-onset DM (HR: 0.40, 95% CI (0.39–0.42), p < 0.001). These results were consistent regardless of the presence of impaired glucose tolerance, age, or obesity. Conclusion: Our study showed higher-than-normal eGFR levels were associated with a lower risk of incidence for new-onset DM regardless of the presence of impaired glucose tolerance, age, or obesity. In general population, higher-than-normal eGFR may be associated with a lower risk of incidence of new-onset DM. [ABSTRACT FROM AUTHOR]

Gambling and its impacts are an important public health issue. The relationship between gambling, problem gambling and gambling harm is complex and dynamic. Replicate prevalence studies are useful for surveillance and monitoring gambling impacts within jurisdictions. The purpose of this study was to compare changes in gambling and problem gambling in the Victorian adult population between 2008 and 2018 by investigating individual gambling activities and exploring their relationship with the Victorian gambling ecosystem. Gambling participation has decreased; problem gambling prevalence has not. Investigation beyond these summary measures reveals important details: (a) Electronic Gaming Machines (EGMs), casino table games, race and sports betting ('high-risk activities'), informal private betting, and Keno, and their associations with problem gambling endure. Further, the strength of this association is unaffected by changes in product technology, delivery, or the Victorian environment in which they reside, (b) participation in high-risk activities, excluding EGMs, increased while for other activities they decreased, (c) EGMs continue to pose the greatest risk for Victorians, (d) males and young adults continue having a higher problem gambling prevalence rate and preferring both online gambling and high-risk activities (excluding racing favoured by an ageing, older cohort, and Keno, by all ages), and (e) gambling access and exposure proliferated enabling single site multiple gambling opportunities on high-risk activities. Young adults represented a new vulnerable group as they reach the legal gambling age. The most effective interventions (based on major falls in real expenditure (losses) on EGMs, the highest risk activity) were the smoking bans, removal of ATMs from venues and decreases in bet size. There is great potential for prevention, intervention, and minimising harm in the gambling environment. [ABSTRACT FROM AUTHOR]

Objective: Computer aided diagnostics (CAD) systems can automate the differentiation of maxillary sinus (MS) with and without opacification, simplifying the typically laborious process and aiding in clinical insight discovery within large cohorts. Methods: This study uses Hamburg City Health Study (HCHS) a large, prospective, long‐term, population‐based cohort study of participants between 45 and 74 years of age. We develop a CAD system using an ensemble of 3D Convolutional Neural Network (CNN) to analyze cranial MRIs, distinguishing MS with opacifications (polyps, cysts, mucosal thickening) from MS without opacifications. The system is used to find correlations of participants with and without MS opacifications with clinical data (smoking, alcohol, BMI, asthma, bronchitis, sex, age, leukocyte count, C‐reactive protein, allergies). Results: The evaluation metrics of CAD system (Area Under Receiver Operator Characteristic: 0.95, sensitivity: 0.85, specificity: 0.90) demonstrated the effectiveness of our approach. MS with opacification group exhibited higher alcohol consumption, higher BMI, higher incidence of intrinsic asthma and extrinsic asthma. Male sex had higher prevalence of MS opacifications. Participants with MS opacifications had higher incidence of hay fever and house dust allergy but lower incidence of bee/wasp venom allergy. Conclusion: The study demonstrates a 3D CNN's ability to distinguish MS with and without opacifications, improving automated diagnosis and aiding in correlating clinical data in population studies. Level of Evidence: 3 Laryngoscope, 134:3927–3934, 2024 [ABSTRACT FROM AUTHOR]

Introduction: Differences in the prevalence of psychiatric conditions such as psychosis as well as patterns of comorbidity for psychosis have been reported between racial and ethnic groups. It is unclear whether those differences are consistent for comorbid psychosis Methods: Self-reported diagnostic data from American adults ages 18-99 participating in the Collaborative Psychiatric Epidemiology Surveys (CPES) (N ~ 11,844) were used to test the association between four racial and ethnic group categories (White, Asian, Hispanic, Black) and comorbid psychosis. Comorbid psychosis was measured as a 4-level categorical variable (No mental illness nor psychosis, Mental Illness, Psychosis only, comorbid psychosis (i.e., Psychosis + Mental Illness). Chi-square tests were used to determine significant differences in the prevalence of comorbid psychosis by race and ethnicity. A multinomial logistic regression was used to test the association between racial and ethnic classifications and comorbid psychosis after adjusting for common demographic characteristics (i.e., education, sex, income, and age). Results: Relative to White participants, Hispanic and Asian participants were less likely to be affected with comorbid psychosis. (Adjusted Odds Ratio, AORAsian = 0.32, CI = 0.22 - 0.47, p <0.0001, AORHispanic = 0.66, CI = 0.48 - 0.92, p = 0.012). Relative to White participants there was not significant association for comorbid psychosis in Black participants (AORBlack = 0.91, CI = 0.70 - 1.20, p = 0.52) In contrast Hispanic and Black participants were more likely to report psychosis alone (AORHispanic = 1.94, CI = 1.27-2.98, p = 0.002, AORBlack = 1.86, 1.24-2.82, p = 0.003) compared to White participants. Conclusion: There were different patterns of associations by race and ethnicity for psychosis and comorbid psychosis. The lower prevalence of comorbid psychosis in non-White groups may be due to underdiagnosis or underreporting of other mental disorders. [ABSTRACT FROM AUTHOR]

Aim: The trial (NCT04016974) investigated the pharmacokinetics, pharmacodynamics, safety and tolerability of oral semaglutide, the first orally administered glucagon‐like peptide‐1 analogue for type 2 diabetes, in healthy Chinese subjects. Materials and Methods: This single‐centre, multiple‐dose, placebo‐controlled trial randomized 32 healthy Chinese adults to once‐daily oral semaglutide (3 mg escalating to 14 mg) or placebo for 12 weeks. Blood samples were collected regularly during treatment and follow‐up. The primary endpoint was the area under the semaglutide concentration–time curve over a dosing interval (0‐24 h) at steady state (AUC0‐24h,sema,SS). Secondary pharmacokinetic endpoints included the maximum observed semaglutide plasma concentration at steady state (Cmax,sema,SS). Supportive secondary pharmacodynamics endpoints included changes in body weight and fasting plasma glucose. Results: Treatment with all oral semaglutide doses showed dose‐dependent increases in semaglutide exposure in healthy Chinese subjects at steady state, determined by AUC0‐24h,sema,SS (233, 552 and 1288 h·nmol/L for 3, 7 and 14 mg of oral semaglutide, respectively) and Cmax,sema,SS. Oral semaglutide treatment was associated with significant reductions in body weight (p =.0001) and fasting plasma glucose (p =.0011) versus placebo at the end of treatment. The safety and tolerability of oral semaglutide were consistent with the known profile of glucagon‐like peptide‐1 receptor agonists, with no severe or blood‐glucose–confirmed symptomatic hypoglycaemic events, serious adverse events or deaths. The most frequent adverse events were gastrointestinal disorders. Conclusions: At steady state, oral semaglutide exposure was dose dependent and close to dose proportionality in healthy Chinese subjects. This is consistent with previous clinical pharmacology results for oral semaglutide. [ABSTRACT FROM AUTHOR]

Abstract This research aimed to systematically uncover the metastatic characteristics and survival rates of lung cancer subtypes and to evaluate the impact of surgery at the primary tumor site on cancer-specific survival in DM lung cancer. We used the Surveillance, Epidemiology, and End Results (SEER) database (2010–2019) to identify primary lung cancers with DM at presentation (M1). Kaplan–Meier (KM) survival curves were generated and compared utilizing log-rank tests. Cox regression methods were employed to determine hazard ratios (HR) and 95% confidence intervals related to CSS factors. Inverse probability of treatment weighting (IPTW) was applied to reduce bias. We analyzed 77,827 M1 lung cancer cases, with 41.22% having DM at presentation. Bone metastasis was most common in ADC, ASC, SCC, LCC; brain in LCNEC; liver in SCLC. Lung was common in TC + AC and SCC. Long-term survival was best in TC + AC and worst in SCLC (p

Abstract Background Education has been shown to be positively associated with cognitive performance. However, the pathways via lifestyle-related disease through which education is related to cognitive performance have not been sufficiently explored. Diabetes is an important lifestyle-related disease with increasing prevalence worldwide. Low education is associated with an increased risk of developing diabetes, while diabetes may also lead to a deterioration in cognitive performance. This study aims to explore if the associations between education and cognitive function is mediated by the diabetes status among older adults. Methods The data utilized in this study were derived from the first two waves of the Dutch Lifelines Cohort Study (2006–2015). The analyzed sample included 26,131 individuals aged 50 years or above at baseline. The baseline assessment included measurements of educational attainment (exposure) and the potential mediator diabetes. The outcome of cognitive function was assessed using age-standardized reaction times from the psychomotor function and attention tasks, as measured by the Cogstate Brief Battery. The Cogstate Brief Battery was only conducted at the follow-up assessment, not at the baseline assessment. Faster reaction times correspond to higher cognitive performance. The study employed linear and logistic regression models, in addition to a causal mediation approach which estimated the average causal mediation effect (ACME). Results Higher education was associated with a lower risk of diabetes (b= -0.1976, 95%CI= -0.3354; -0.0597) compared to low or middle education as well as with faster reaction times (b= -0.2023, 95%CI= -0.2246; -0.1798), implying better cognitive function. Diabetes was associated with slower reaction times (b = 0.0617, 95%CI = 0.0162; 0.1072). Most importantly, the mediation approach identified a significant indirect effect of education on cognitive function via the diabetes status (ACME= -0.00061, 95%CI= -0.00142; -0.00011). Discussion The findings emphasize the potentially importance of diabetes in explaining the role of education in promoting healthy cognitive function and mitigating the risk of cognitive decline. Early detection and treatment of diabetes may be particularly beneficial for individuals with low or middle levels of education in order to maintain good levels of cognitive function.

Aim: To assess the prevalence of individual obesity‐related complications (ORCs) and multimorbidity (≥ 1, ≥ 2 and ≥ 3 ORCs), and multimorbidity‐associated healthcare costs, over 10 years. Methods: This retrospective open cohort study used Discover, a UK database of linked primary and secondary electronic health records. Adults were stratified by body mass index (BMI; overweight: 25‐< 30 kg/m2; obesity class I: 30‐< 35 kg/m2; obesity class II: 35‐< 40 kg/m2; obesity class III: ≥ 40 kg/m2). Outcomes by year since baseline were assessed for serial cross sections across the study period (1 January 2004 to 31 December 2019; the index date was the date of first eligible BMI measurement). Results: Across 1 410 146 individuals (overweight: 1 008 101; obesity class I: 278 782; obesity class II: 80 621; obesity class III: 42 642), ORC prevalence was higher in successive BMI groups, and increases over time were generally greater for obesity relative to overweight. In those with ORC multimorbidity, both higher BMI and the presence of more ORCs were associated with higher annual per‐person healthcare costs. Costs increased over time in those individuals with obesity and one or more ORC, as well as in those with obesity and two or more ORCs. Conclusions: Higher BMI was associated with higher baseline ORC prevalence and a greater increase in ORC prevalence over time, and with higher healthcare costs in those with multimorbidity. To reduce the burden of overweight and obesity on patients and healthcare systems, the presence, number and type of ORCs should be considered in developing effective, targeted prevention and management care pathways. [ABSTRACT FROM AUTHOR]

Aims: To estimate healthcare resource utilization (HCRU) and healthcare costs by body mass index (BMI) in a UK cohort and to explore how this varied by defined BMI strata. Materials and Methods: This retrospective open cohort study used Discover, a linked primary and secondary electronic health records database covering 2.7 million individuals. Adults were stratified by BMI as: overweight (25–<30 kg/m2); obesity class I (30–<35 kg/m2); obesity class II (35–<40 kg/m2); or obesity class III (≥40 kg/m2). Cost data, comprising primary care, secondary care (inpatient admissions, outpatient appointments and emergency room visits) and prescriptions, were reported for 2015–2019. Results: Overall, 1 008 101 individuals were overweight, 278 782 had obesity class I; 80 621 had obesity class II, and 42 642 had obesity class III. Healthcare costs and HCRU events per person per year increased over time (2015: £851–£1321 and 10.6–13.4 events; 2019: £1143–£1871 and 11.4–14.9 events), and were higher for each successive BMI group. Groups with chronic kidney disease or cardiovascular disease incurred particularly high costs. In 270 493 individuals with obesity in 2019, more than 72% of total healthcare costs were incurred by the highest cost quintile, which had a higher mean age and more obesity‐related complications (ORCs) than lower cost quintiles. Conclusions: The economic impact of obesity could be alleviated by weight management support based on unmet need, to limit the effects of BMI progression and ORC development. [ABSTRACT FROM AUTHOR]

Abstract Background Nine in every thousand children born in the United Kingdom have congenital heart disease, and 250,000 adults are living with the condition. This study aims to investigate the associations between congenital heart disease and educational outcomes among school-aged children in Scotland. Methods Routine health and education databases were linked to produce a cohort of all singleton children born in Scotland and attending a local authority run primary, secondary, or special school in Scotland at some point between 2009 and 2013. Children with congenital heart disease within this cohort were compared with children unaffected by congenital conditions. Outcomes investigated were special educational need (SEN), absenteeism, exclusion, academic attainment, and unemployment. All analyses were adjusted for sociodemographic and maternity confounders. Absenteeism was investigated as a mediating factor in the associations with attainment and unemployment. Results Of the 715,850 children, 6,295 (0.9%) had congenital heart disease and 4,412 (6.1%) had isolated congenital heart disease. Congenital heart disease and isolated congenital heart disease were both significantly associated with subsequent special educational need (OR 3.45, 95% CI 3.26–3.65, p

AbstractObjectiveDesignSubjectsMethodsResultsConclusion\nKEY POINTSTo investigate whether mental and work-related stress predicts a one-year incidence of sick leave in a cohort of middle-aged working women.The 2016/17 survey was part of the Population Study of Women in Gothenburg, Sweden, with registry data information on sick leave during one year pre- and post-baseline.A cohort of women aged 38 and 50 in 2016/17 (n = 573; 68% participation), of which 504 women were gainfully employed and not on sick leave ± 2 weeks around baseline examination; 493 women had complete data on stress exposure.We studied associations between self-assessed mental and work-related stress and incident sick leave of >14 days during the year following the baseline examination. We used multiple logistic regression, adjusting for age and previous sick leave, and additionally for sleep quality, well-being, and physical activity.Overall, 75 women (16%) experienced at least one period of sick leave after baseline. Permanent stress during the last five years almost tripled the risk for incident sick leave, OR = 2.8 (95% CI 1.2–6.3), independent of previous sick leave, OR = 2.3 (95% CI 1.3–4.2). Among 21 specific work-related problems, conflicts at work, OR = 2.2 (95% CI 1.3–3.6), and low decision latitude, OR = 1.7 (95% CI 1.0–2.9), were associated with incident sick leave. The association with conflicts at work remained upon further covariate adjustment.Low decision latitude and conflicts at work are risk factors for incident sick leave among working women. The impact of conflicts at work, irrespective of own involvement, may indicate a specific vulnerability among women of interest for future interventions.About 75% of around 500 middle-aged women reported mental stress in 2016/17. Low decision latitude and conflicts at work predicted incident sick leave independent of general mental stress and previous periods of sick leave. Efforts to improve the work environment may be essential for interventions aiming to reduce absenteeism among working women. [ABSTRACT FROM AUTHOR]

Probiotics and prebiotics offer a range of advantageous effects on human health. The knowledge, attitudes, and practices (KAP) of individuals can impact their inclination to consume probiotics and prebiotics. The main objective of this study was to examine the KAP of the people in the United Arab Emirates (UAE) about probiotics and prebiotics consumption. Additionally, the study aimed to assess the impact of KAP and sociodemographic factors on the use of probiotics and prebiotics. In order to accomplish this objective, a verified online questionnaire was used with a five-point Likert scale and distributed using an online platform (Google Forms). A cross-sectional research, non-probability sampling was implemented, and G*Power statistical power analysis was used to estimate a sample size of 385 participants. A total of 408 replies were gathered. The population under study consisted of residents in the UAE between the ages of 18 to 64 years old, excluding populations under the age of 18 and those living outside the UAE. A total of 392 participants met the criteria for inclusion in this study. The research ethics committees of UAE University granted the study approval (ERSC_2024_4359), and the validity of the findings was confirmed through face-to-face interviews with around 50 individuals and a Cronbach's alpha test with result of 0.84. The statistical software SPSS version 29.0 for Mac OS was utilized to examine the relationships between KAP variables, including Chi-square tests and Pearson's correlation coefficients. The tests were selected based on their capacity to handle categorical and continuous data, respectively. The female population was 85.2% of the total, while the male population accounts for 14.8%. The age distribution of participants shows that the largest proportion, 68.4%, falls within the 18–24 age range. Out of the participants, 61.5% held a bachelor's degree. Most of the participants, 56.4%, were students, while 29.1% were employees. The average results indicate a significant inclination towards probiotics and prebiotics, as demonstrated by the scores above the midpoint for the six knowledge questions (M = 2.70), six attitude questions (M = 3.10), and six practice questions (M = 3.04). Several studies have examined this phenomenon; however, additional research comparing individuals in the UAE is necessary to fully comprehend the influence of KAP on the consumption of probiotics and prebiotics in the UAE. [ABSTRACT FROM AUTHOR]

Background and aims: Varenicline is one of the most effective smoking cessation treatments. Its supply in England was disrupted in July 2021 due to nitrosamine impurities found by its supplier, Pfizer. This study measured the impact of this disruption on smoking cessation in England. Design, setting and participants: The study used repeated cross‐sectional surveys conducted monthly, from June 2018 to December 2022. Set in England, it comprised a total of 3024 adults who reported smoking during the past year and had made at least one serious attempt to quit in the past 6 months. Measurements: Generalized additive models analyzed the association of the varenicline supply disruption with the trend in self‐reported varenicline use in the most recent quit attempt. We used these results to estimate the population‐level impact of the disruption on smoking cessation. Findings Before July 2021, the proportion of past 6‐month quit attempts using varenicline was stable at approximately 3.9% [risk ratio (RR)trend = 1.034, 95% confidence interval (CI) = 0.823–1.298]. The trend in varenicline use has changed sharply since the supply disruption (RRΔtrend = 0.297, 95% CI = 0.120–0.738), with prevalence falling by 69.3% per year since; from 4.1% in June 2021 to 0.8% in December 2022. Convergently, National Health Service general practitioner prescribing data reported that just 0.1% of prescriptions for smoking cessation treatments in December 2022 were for varenicline. Assuming that varenicline does not return to the market, we estimate that this could result in ~8400 fewer people stopping smoking for at least 6 months, ~4200 fewer long‐term ex‐smokers and ~1890 more avoidable deaths each year. Conclusions: In England, the disruption in supply of varenicline since 2021 has coincided with a substantial fall in the use of varenicline in attempts to quit smoking. [ABSTRACT FROM AUTHOR]

Aim: To prospectively assess the association of smoking timing with the risk of type 2 diabetes (T2D) and examine whether smoking amount or genetic susceptibility might modify the relationship. Materials and Methods: A total of 294 815 participants without diabetes from the UK Biobank, including non‐smokers and smokers with data on the time from waking to first cigarette, were included. Cox proportional hazards models were used to evaluate the association between smoking timing and the risk of incident T2D. Results: During a median follow‐up time of 12 years, a total of 9937 incident cases of T2D were documented. Compared with non‐smokers, a shorter time from waking to first cigarette was significantly associated with a higher risk of incident T2D (P for trend <.001). In the fully adjusted model, the hazard ratios (HRs) (95% confidence interval) associated with smoking timing were 1.46 (1.17–1.81) for more than 2 hours, 1.51 (1.21–1.87) for 1–2 hours, 1.58 (1.34–1.85) for 30–60 minutes, 1.86 (1.57–2.21) for 5–15 minutes and 2.01 (1.60–2.54) for less than 5 minutes. We found that even among those who reported being light smokers, those with the shortest time from waking to first cigarette had a 105% higher risk of T2D with an HR of 2.05 (1.52–2.76), which was comparable with heavy smokers. The genetic risk score for T2D did not modify this association (P‐interaction =.51). Conclusions: Our findings indicate that shorter time from waking to first cigarette is significantly associated with a higher risk of incident T2D. [ABSTRACT FROM AUTHOR]

Transition of young people with chronic kidney disease (CKD) from paediatric to adult healthcare has been associated with poor outcomes, but few population-level studies examine trends in subgroups. We aimed to assess sociodemographic inequalities in changes in unplanned secondary care utilisation occurring across transfer to adult care for people with CKD in England. A cohort was constructed from routine healthcare administrative data in England of young people with childhood-diagnosed CKD who transitioned to adult care. The primary outcome was the number of emergency inpatient admissions and accident and emergency department (A&E) attendances per person year, compared before and after transfer. Injury-related and maternity admissions were excluded. Outcomes were compared via sociodemographic data using negative binomial regression with random effects. The cohort included 4505 individuals. Controlling for age, birth year, age at transfer, region and sociodemographic factors, transfer was associated with a significant decrease in emergency admissions (IRR 0.75, 95% CI 0.64–0.88) and no significant change in A&E attendances (IRR 1.10, 95% CI 0.95–1.27). Female sex was associated with static admissions and increased A&E attendances with transfer, with higher admissions and A&E attendances compared to males pre-transfer. Non-white ethnicities and higher deprivation were associated with higher unplanned secondary care use. Conclusion: Sociodemographic inequalities in emergency secondary care usage were evident in this cohort across the transition period, independent of age, with some variation between admissions and A&E use, and evidence of effect modification by transfer. Such inequalities likely have multifactorial origin, but importantly, could represent differential meetings of care needs. What is Known: • In chronic kidney disease (CKD), transfer from paediatric to adult healthcare is associated with declining health outcomes. • Known differences in CKD outcomes by sociodemographic factors have limited prior exploration in the context of transfer. What is New: • Population-level data was used to examine the impacts of transfer and sociodemographic factors on unplanned secondary care utilisation in CKD. • Healthcare utilisation trends may not reflect known CKD pathophysiology and there may be unexplored sociodemographic inequalities in the experiences of young people across transfer. [ABSTRACT FROM AUTHOR]

Background: Nine in every thousand children born in the United Kingdom have congenital heart disease, and 250,000 adults are living with the condition. This study aims to investigate the associations between congenital heart disease and educational outcomes among school-aged children in Scotland. Methods: Routine health and education databases were linked to produce a cohort of all singleton children born in Scotland and attending a local authority run primary, secondary, or special school in Scotland at some point between 2009 and 2013. Children with congenital heart disease within this cohort were compared with children unaffected by congenital conditions. Outcomes investigated were special educational need (SEN), absenteeism, exclusion, academic attainment, and unemployment. All analyses were adjusted for sociodemographic and maternity confounders. Absenteeism was investigated as a mediating factor in the associations with attainment and unemployment. Results: Of the 715,850 children, 6,295 (0.9%) had congenital heart disease and 4,412 (6.1%) had isolated congenital heart disease. Congenital heart disease and isolated congenital heart disease were both significantly associated with subsequent special educational need (OR 3.45, 95% CI 3.26–3.65, p < 0.001 and OR 1.98, 95% CI 1.84–2.13, p < 0.001 respectively), absenteeism (IRR 1.13, 95% CI 1.10–1.16, p < 0.001 and IRR 1.10, 95% CI 1.06–1.13, p < 0.001 respectively), and low academic attainment (OR 1.69, 95% CI 1.39–2.07, p < 0.001 and OR 1.35, 95% CI 1.07–1.69, p = 0.011 respectively). Neither congenital heart disease nor isolated congenital heart disease were associated with school exclusion. Only congenital heart disease (OR 1.21, 95% CI 1.03–1.42, p = 0.022) but not isolated congenital heart disease was associated with unemployment. When days absent were included in the analyses investigating attainment and unemployment, the conclusions were not altered. Conclusion: Children with congenital heart disease have greater special educational need, lower school attendance, attain lower examination grades and have greater unemployment compared to peers. In addition to healthcare support, affected children need educational support to avoid additional impact on their long-term wellbeing. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) have been implicated in chronic diseases in adults, but their role in paediatric populations remains uncertain. This study, conducted on the Italian sample of the I.Family project, aimed to investigate the relationship between dietary and urinary fluorescent AGEs in children and adolescents. The secondary objective was to investigate the sources of dietary AGEs (dAGEs) and their association with dietary composition and anthropometric parameters. Dietary data were collected from 1048 participants via 24 h dietary recall in 2013/2014 to estimate dAGEs intake, while urinary fluorescent AGE levels were measured in 544 individuals. Participants were stratified based on dAGEs intake and compared with respect to urinary fluorescent AGE levels, anthropometric measurements, and dietary intake. The results showed no significant correlation between dietary and urinary fluorescent AGE levels, nor between dAGEs and anthropometric parameters. Notably, higher dAGEs were associated with a diet richer in protein (especially from meat sources) and fat and lower in carbohydrates. In addition, the consumption of ultra-processed foods was lower in participants with a higher DAGE intake. This study highlights the lack of a clear association between dietary and urinary fluorescent AGEs in children, but suggests a distinctive dietary pattern associated with increased dAGEs intake. Further investigation is warranted to elucidate the potential health implications of dAGEs in paediatric populations. [ABSTRACT FROM AUTHOR]

Aim: To explore the relationship between proinflammatory diet, habitual salt intake and the onset of type 2 diabetes. Methods: This prospective study was conducted among 171 094 UK Biobank participants who completed at least one 24‐h dietary questionnaire and were free of diabetes at baseline. Participants were followed up until 1 March 2023 for type 2 diabetes incidence, with diagnosis information obtained from linked medical records. An Energy‐adjusted Diet Inflammatory Index (E‐DII) was calculated based on 28 food parameters. Habitual salt intake was determined through the self‐reported frequency of adding salt to foods. The associations between E‐DII, habitual salt intake and type 2 diabetes incidence were tested by the Cox proportional hazard regression model. Results: Over a median follow‐up period of 13.5 years, 6216 cases of type 2 diabetes were documented. Compared with participants with a low E‐DII (indicative of an anti‐inflammatory diet), participants with a high E‐DII (indicative of a proinflammatory diet) had an 18% heightened risk of developing type 2 diabetes. The association between E‐DII and type 2 diabetes tends to be linear after adjustment for major confounders. Participants with a proinflammatory diet and always adding salt to foods had the highest risk of type 2 diabetes incidence (hazard ratio 1.60, 95% confidence interval 1.32‐1.94). Conclusions: Our findings indicate that a proinflammatory diet and higher habitual salt intake were associated with an increased risk of type 2 diabetes. These results support the public health promotion of an anti‐inflammatory diet and reducing salt intake to prevent the onset of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: To determine the magnitude of the association between abdominal adiposity and low‐grade inflammation in persons with recently diagnosed type 2 diabetes (T2D) and to determine to what extent this association is mediated by low physical activity level, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, hypertension, and comorbidities. Materials and Methods: We measured waist circumference, clinical characteristics, and inflammatory markers i.e. tumour necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), and high‐sensitivity C‐reactive protein (hsCRP), in >9000 persons with recently diagnosed T2D. We applied multiple mediation analysis using structural equation modelling, with adjustment for age and sex. Results: Waist circumference as a proxy for abdominal adiposity was positively associated with all inflammatory markers. Hence, a one‐standard deviation (SD) increase in waist circumference (SD = 15 cm) was associated with a 22%, 35%, and 46% SD increase in TNF‐α (SD = 1.5 pg/mL), IL‐6 (SD = 4.4 pg/mL), and hsCRP (SD = 6.9 mg/L), respectively. The level of hyperinsulinaemia assessed by fasting C‐peptide was quantitatively the most important mediator, accounting for 9%–25% of the association between abdominal adiposity and low‐grade inflammation, followed by low physical activity (5%–7%) and high triglyceride levels (2%–6%). Although mediation of adiposity‐induced inflammation by greater comorbidity and higher glycated haemoglobin levels reached statistical significance, their impact was minor (1%–2%). Conclusions: In persons with recently diagnosed T2D, there was a clear association between abdominal adiposity and low‐grade inflammation. A considerable part (20%–40%) of this association was mediated by other factors, with hyperinsulinaemia as a potentially important driver of adiposity‐induced inflammation in T2D. [ABSTRACT FROM AUTHOR]

The rise of online gambling has drawn attention towards offshore gambling. Currently there is lack of evidence on reasons and motivations to gamble on offshore gambling sites. This study investigated the general gambling motives of onshore and offshore gamblers, and the reasons to gamble on offshore gambling sites. The study used binary logistic regression model to analyze the data from Finnish Gambling 2019 population survey including adult past-year online gamblers (n = 1,422). The validated measure for problem gambling severity (PGSI, Problem Gambling Severity Index) was used. Furthermore, data-driven qualitative analysis was used to form categories for the reasons to gamble on offshore gambling sites. Offshore gambling was more common among men and younger age groups than among women or older age groups. Offshore gamblers gambled less often for money or worthy causes than onshore gamblers. Furthermore, offshore gamblers had more different types of motives to gamble, they gambled more frequently and had higher problem gambling severity scores (PGSI) than onshore gamblers. Finally, the most common reasons to gamble offshore were: (1) larger game supply and game features, (2) benefits, bonuses, and the usability of the website, and (3) inner motivation. Offshore gambling is characterized with intensity and diversity of gambling behavior and motives, and it poses a risk especially for young men. [ABSTRACT FROM AUTHOR]

Background and Purpose: Recent studies have suggested an association between dysfunction of the choroid plexus and the glymphatic system. However, information is inconclusive. Following a population-based study design, we aimed to assess the association between choroid plexus calcifications (CPCs)—as a surrogate of choroid plexus dysfunction—and severity and progression of putative markers of glymphatic dysfunction, including white matter hyperintensities (WMH) of presumed vascular origin and abnormally enlarged basal ganglia perivascular spaces (BG-PVS). Methods: This study recruited community-dwellers aged ≥40 years living in neighboring Ecuadorian villages. Participants who had baseline head CTs and brain MRIs were included in cross-sectional analyses and those who additional had follow-up MRIs (after a mean of 6.4 ± 1.5 years) were included in longitudinal analyses. Logistic and Poisson regression models, adjusted for demographics and cardiovascular risk factors, were fitted to assess associations between CPCs and WMH and enlarged BG-PVS severity and progression. Results: A total of 590 individuals were included in the cross-sectional component of the study, and 215 in the longitudinal component. At baseline, 25% of participants had moderate-to-severe WMH and 27% had abnormally enlarged BG-PVS. At follow-up, 36% and 20% of participants had WMH and enlarged BG-PVS progression, respectively. Logistic regression models showed no significant differences between CPCs volumes stratified in quartiles and severity of WMH and enlarged BG-PVS. Poisson regression models showed no association between the exposure and WMH and enlarged BG-PVS progression. Baseline age remained significant in these models. Conclusions: Choroid plexus calcifications are not associated with putative markers of glymphatic system dysfunction. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) patients suffer high risks of mortality. Ondansetron has been verified to be effective in improving the prognosis of some kinds of critically ill patients. We design this study to explore whether ondansetron use is associated with lower risks of mortality among TBI patients. Methods: TBI patients from the Medical Information Mart for Intensive Care-III were collected. The usage of ondansetron, including intravenous injection and oral tablet, since admission to the Beth Israel Deaconess Medical Center between 2001 and 2012 was identified. Univariate and multivariate logistic regression were performed to analyze the relationship between the ondansetron use and mortality of TBI patients. Propensity score matching (PSM) was utilized to generate balanced cohorts of the non-ondansetron use group and ondansetron use group. Sub-group analysis was performed to verify the association between the ondansetron use and mortality of TBI patients in different TBI severity levels after PSM. Results: In TBI cohorts before PSM, the usage incidence of ondansetron was 37.2%. The 30-day mortality was significantly lower in the ondansetron group (p < 0.001). The multivariate logistic regression showed that ondansetron was associated with the lower mortality of TBI patients (p = 0.008). In TBI cohorts after PSM, the 30-day mortality of the ondansetron group was lower than that of the non-ondansetron group, although without statistical significance (p = 0.079). Logistic regression indicated ondansetron use was significantly associated with the lower mortality of moderate-to-severe TBI (p < 0.001) but not mild TBI (p = 0.051). In addition, Cox regression also presented that ondansetron use was significantly associated with the lower mortality of moderate-to-severe TBI (p < 0.001) but not mild TBI (p = 0.052). Conclusion: Ondansetron usage is associated with a lower mortality risk of moderate-to-severe TBI but not mild TBI patients. Ondansetron may be a novel adjunctive therapeutic strategy to improve the prognosis of moderateto-severe TBI patients. [ABSTRACT FROM AUTHOR]

Background: End stage ankle osteoarthritis (OA) is debilitating. Surgical management consists of either ankle arthrodesis (AA) or a total ankle replacement (TAR). The purpose of this study is to assess the trends in operative intervention for end stage ankle OA in an Australian population. Methods: This is a retrospective epidemiological study of 15,046 surgeries. Data were collected from publicly available national registries including the Australian Medicare Database and Australian Orthopaedic Association National Joint Replacement Registrar from 2001 to 2020. Results: There was a significant increase in all ankle surgeries performed across the period of interest. AA remained the more commonly performed procedure throughout the course of the study (11,946 cases, 79.4%) and was never surpassed by TAR (3100, 20.6%). The overall proportions demonstrated no significant changes from 2001 to 2020. Conclusion: The incidence of ankle surgeries continues to increase with the ageing and increasingly comorbid population of Australia. Despite demonstrating no significant overall change in the ratio of TAR and AA in our study population and period, there are noticeable trends within the timeframe, with a recent surge favouring TAR in the last 5 years. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is there a difference in the time interval between the first and second live births among individuals with and without recurrent pregnancy loss (RPL)? SUMMARY ANSWER Primary RPL (two or more pregnancy losses before the first live birth) is associated with a shorter time interval between the first and second live births compared with individuals without RPL, but this association is reversed in patients with secondary RPL (RPL patients with no or one pregnancy loss before the first live birth). WHAT IS KNOWN ALREADY There is limited information regarding the ability to have more than one child for patients with RPL. Previous studies have investigated the time to live birth and the live birth rate from the initial presentation to clinical providers. Most of the previous studies have included only patients treated at specialized RPL clinics and thus may be limited by selection bias, including patients with a more severe condition. STUDY DESIGN, SIZE, DURATION We conducted a population-based retrospective cohort study of 184 241 participants who delivered in British Columbia, Canada, and had at least two recorded live births between 2000 and 2018. The aim was to study the differences in the time interval between the first and second live births and the prevalence of pregnancy complications in patients with and without RPL. Additionally, 198 319 individuals with their first live birth between 2000 and 2010 were studied to evaluate cumulative second live birth rates. PARTICIPANTS/MATERIALS, SETTING, METHODS Among individuals with at least two recorded live births between 2000 and 2018, 12 321 patients with RPL and 171 920 participants without RPL were included. RPL was defined as at least two pregnancy losses before 20 weeks gestation. Patients with primary RPL had at least two pregnancy losses occurring before the first live birth, while patients with secondary RPL had no or one pregnancy loss before the first live birth. We compared the time interval from the first to second live birth in patients with primary RPL, those with secondary RPL, and participants without RPL using generalized additive models to allow for a non-linear relationship between maternal age and time interval between first and second live births. We also compared prevalence of pregnancy complications at the first and second live births between the groups using non-parametric Kruskal–Wallis H test and Fisher's exact test for continuous and categorical variables, respectively. We assessed the cumulative second live birth rates in patients with primary RPL and those without RPL, among participants who had their first live birth between 2000 and 2010. Cox proportional hazards model was used to estimate and compare hazard ratios between the two groups using a stratified modelling approach. MAIN RESULTS AND THE ROLE OF CHANCE The adjusted time interval between the first and second live births was the longest in patients with secondary RPL, followed by individuals without RPL, and the shortest time interval was observed in patients with primary RPL: 4.34 years (95% CI: 4.09–4.58), 3.20 years (95% CI: 3.00–3.40), and 3.05 years (95% CI: 2.79–3.32). A higher frequency of pregnancy losses was associated with an increased time interval between the first and second live births. The prevalence of pregnancy complications at the first and second live births, including gestational diabetes, hypertensive disorder of pregnancy, preterm birth, and multiple gestations was significantly higher in patients with primary RPL compared with those without RPL. The cumulative second live birth rate was significantly lower in patients with primary RPL compared with individuals without RPL. LIMITATIONS, REASONS FOR CAUTION This study may be limited by its retrospective nature. Although we adjusted for multiple potential confounders, there may be residual confounding due to a lack of information about pregnancy intentions and other factors, including unreported pregnancy losses. WIDER IMPLICATIONS OF THE FINDINGS The results of this study provide information that will help clinicians in the counselling of RPL patients who desire a second child. STUDY FUNDING/COMPETING INTEREST(S) This study was supported in part by a grant from the Canadian Institutes of Health Research (CIHR): Reference Number W11-179912. M.A.B. reports research grants from CIHR and Ferring Pharmaceutical. He is also on the advisory board for AbbVie, Pfizer, and Baxter. The other authors report no conflict of interest. TRIAL REGISTRATION NUMBER NCT04360564. [ABSTRACT FROM AUTHOR]

BACKGROUND: Children in low-resource countries like Georgia often have limited access to assessment measures for mental health care services. This study adapts and validates the mental health screening tool the Strength and Difficulties Questionnaire for use in Georgian children. METHODS: A total of 16 654 children were assessed by a parent and/or teacher using Georgian-adapted Strength and Difficulties Questionnaire. Receiver operating characteristic analyses were performed to assess the discriminative validity of the Strength and Difficulties Questionnaires and to establish an optimal cutoff score. RESULTS: Data from 15 738 parents- and 13 560 teachers-administered Strength and Difficulties Questionnaire were analyzed. The internal consistency analysis showed Cronbachs alpha to be 0.625 and 0.621 for parent- and teacher-administered Strength and Difficulties Questionnaire, respectively. The area under the curve (95% CI) shows that the Strength and Difficulties Questionnaire can differentiate risk group children from typically developing peers: parent-administered questionnaires-0.629 (0.556-0.702) and teacher-administered questionnaires-0.680 (0.611-0.789). Parent-administered Strength and Difficulties Questionnaire has a cutoff value of 16 or more with 92.5% of sensitivity and teacher-administered Strength and Difficulties Questionnaire-14 or more with a sensitivity of 85.6%. CONCLUSION: The study finds that the Strength and Difficulties Questionnaire is a valid screening instrument and does not depend on the informant-parent or teacher. It suggests that with appropriate cultural adaptation, the SDQ can be used in the Republic of Georgia to identify children at risk for mental disorders and help guide resource allocation.

IntroductionMonitoring the pharmacotherapy adherence in society is crucial for identifying occurance and causes of potential inadequate use of drugs and inform providers about the need for better customer counceling. It is necessary component of the strategic planning of the quality of healthcare services. This population- based study aimed to assess the medication intake adherence in the Republic of Serbia and the individual factors and health system variables influencing its pattern.MethodsWe applied a cross-sectional approach to study medication intake adherence using a secondary analysis of the latest 2019 Serbian National Health Survey data. The statistical modeling of the pharmacotherapy adherence incorporated sociodemographic data, self-reported disease, and lifestyle behavior.ResultsIn 2019, in the representative sample of 12,066 adults in Serbia, requiring prescribed medicine, 49.8% did comply with the prescribed drugs, and 50.2% do not. Participants who adhered to prescribed medication were significantly (p

This research letter discusses a study that explores the suicide rates among individuals with diabetes in the United States. The study reveals that individuals with diabetes have a higher risk of suicide compared to the general population. The risk is particularly elevated among White patients with diabetes, but diabetes is a larger risk factor for suicide among Black patients. Additionally, females with diabetes are more susceptible to suicide than males, and all levels of urbanization are associated with a higher suicide risk. The study suggests that targeted interventions for at-risk populations could help reduce suicide rates among individuals with diabetes. However, the study has limitations, such as the lack of differentiation between type 1 and type 2 diabetes in the data and the inability to establish a causal relationship between diabetes and suicide. The authors emphasize the urgent need for action from policymakers, investigators, and healthcare professionals to address the growing burden of both diabetes and suicide in the United States. [Extracted from the article]

Abstract Background Early-onset dementia (EOD, onset age

Abstract Large-scale copy number variants (CNVs) are structural alterations in the genome that involve the duplication or deletion of DNA segments, contributing to genetic diversity and playing a crucial role in the evolution and development of various diseases and disorders, as they can lead to the dosage imbalance of one or more genes. Massively parallel sequencing (MPS) has revolutionized the field of genetic analysis and contributed significantly to routine clinical diagnosis and screening. It offers a precise method for detecting CNVs with exceptional accuracy. In this context, a non-invasive prenatal test (NIPT) based on the sequencing of cell-free DNA (cfDNA) from pregnant women’s plasma using a low-coverage whole genome MPS (WGS) approach represents a valuable source for population studies. Here, we analyzed genomic data of 12,732 pregnant women from the Slovak (9,230), Czech (1,583), and Hungarian (1,919) populations. We identified 5,062 CNVs ranging from 200 kbp and described their basic characteristics and differences between the subject populations. Our results suggest that re-analysis of sequencing data from routine WGS assays has the potential to obtain large-scale CNV population frequencies, which are not well known and may provide valuable information to support the classification and interpretation of this type of genetic variation. Furthermore, this could contribute to expanding knowledge about the central European genome without investing in additional laboratory work, as NIPTs are a relatively widely used screening method.

Abstract Background Low muscle mass is associated with adverse health outcomes such as functional decline and all-cause mortality. This study investigated the relationship between the risk of low muscle mass and the training period and/or frequency of resistance training (RT). Methods We included 126,339 participants (81,263 women) from nationwide cohorts in Korea. Low muscle mass was defined based on the fat-free mass index. To investigate the presence of an inverse dose–response relationship between RT levels and the risk of low muscle mass, the training period (months) and frequency (per week) of RT were used. Multiple logistic regression models were used to assess the risk of low muscle mass according to the RT levels. Results Prevalence rates for low muscle mass in our study population were 21.27% and 6.92% in men and women, respectively. When compared with not performing RT, performing RT for 3–4 days/week and ≥5 days/week decreased the risk of low muscle mass by 22% and 27%, respectively, and performing RT for 12–23 months and ≥24 months decreased the risk by 19% and 41%, respectively. When simultaneously considering both training period and frequency, performing RT for either 3–4 days/week or ≥5 days/week was significantly related to risk reduction, provided that the training period was at least 1 year. Importantly, performing RT for more than 2 years resulted in an additional risk reduction. However, there was no additional effect of performing RT for ≥5 days/week compared to 3–4 days/week, regardless of whether the RT duration was 1–2 years or more than 2 years. Conclusions Since performing RT for 5 days/week or more did not yield any additional effects on the risk of low muscle mass, performing RT for 3–4 days/week was sufficient to prevent low muscle mass. The effectiveness of this preventive measure can be further enhanced by engaging in long-term RT, specifically for more than 2 years.

This document is an editorial published in the journal Frontiers in Plant Science. It discusses the analysis of plastomes, which are the genomes of plant chloroplasts, and related bioinformatics tools. The editorial emphasizes the importance of comprehensive studies on plastomes for plant phylogenetic reconstruction and molecular identification. It also mentions the challenges in assembling and analyzing plastomes with unique features and introduces a research topic on this subject, which includes ten research articles. The document suggests that future research should focus on studying plastomes in parasitic plants, saprophytic plants, and plants living in extreme environments. [Extracted from the article]

Large-scale copy number variants (CNVs) are structural alterations in the genome that involve the duplication or deletion of DNA segments, contributing to genetic diversity and playing a crucial role in the evolution and development of various diseases and disorders, as they can lead to the dosage imbalance of one or more genes. Massively parallel sequencing (MPS) has revolutionized the field of genetic analysis and contributed significantly to routine clinical diagnosis and screening. It offers a precise method for detecting CNVs with exceptional accuracy. In this context, a non-invasive prenatal test (NIPT) based on the sequencing of cell-free DNA (cfDNA) from pregnant women's plasma using a low-coverage whole genome MPS (WGS) approach represents a valuable source for population studies. Here, we analyzed genomic data of 12,732 pregnant women from the Slovak (9,230), Czech (1,583), and Hungarian (1,919) populations. We identified 5,062 CNVs ranging from 200 kbp and described their basic characteristics and differences between the subject populations. Our results suggest that re-analysis of sequencing data from routine WGS assays has the potential to obtain large-scale CNV population frequencies, which are not well known and may provide valuable information to support the classification and interpretation of this type of genetic variation. Furthermore, this could contribute to expanding knowledge about the central European genome without investing in additional laboratory work, as NIPTs are a relatively widely used screening method. [ABSTRACT FROM AUTHOR]

Aim: Socio‐economic status (SES) influences diabetes onset, progression and treatment. In this study, the associations between SES and use of hospital care were assessed, focusing on hospitalizations, technology and cardiovascular complications. Materials and Methods: This was an observational cohort study comprising 196 695 patients with diabetes (all types and ages) treated in 65 hospitals across the Netherlands from 2019 to 2020 using reimbursement data. Patients were stratified in low, middle, or high SES based on residential areas derived from four‐digit zip codes. Results: Children and adults with low SES were hospitalized more often than patients with middle or high SES (children: 22%, 19% and 15%, respectively; p <.001, adults: 28%, 25% and 23%; p <.001). Patients with low SES used the least technology: no technology in 48% of children with low SES versus 40% with middle SES and 38% with high SES. In children, continuous subcutaneous insulin infusion (CSII) and real‐time continuous glucose monitoring (rtCGM) use was higher in high SES {CSII: odds ratio (OR) 1.54 [95% confidence interval (CI) 1.35‐1.76]; p <.001; rtCGM OR 1.39 [95% CI 1.20‐1.61]; p <.001} and middle SES [CSII: OR 1.41 (95% CI 1.24‐1.62); p <.001; rtCGM: OR 1.27 (95% CI 1.09‐1.47); p =.002] compared with low SES. Macrovascular (OR 0.78 (95% CI 0.75‐0.80); p <.001) and microvascular complications [OR 0.95 (95% CI 0.93‐0.98); p <.001] occurred less in high than in low SES. Conclusions: Socio‐economic disparities were observed in patients with diabetes treated in Dutch hospitals, where basic health care is covered. Patients with low SES were hospitalized more often, used less technology, and adults with high SES showed fewer cardiovascular complications. These inequities warrant attention to guarantee equal outcomes for all. [ABSTRACT FROM AUTHOR]

Aim: To characterize the impact of the COVID‐19 pandemic on diabetes diagnosis using data from Alberta's Tomorrow Project (ATP), a population‐based cohort study of chronic diseases in Alberta, Canada. Materials and Methods: The ATP participants who were free of diabetes on 1 April 2018 were included in the study. A time‐segmented regression model was used to compare incidence rates of diabetes before the COVID‐19 pandemic, during the first two COVID‐19 states of emergency, and in the period when the state of emergency was relaxed, after adjusting for seasonality, sociodemographic factors, socioeconomic status, and lifestyle behaviours. Results: Among 43 705 ATP participants free of diabetes (65.5% females, age 60.4 ± 9.5 years in 2018), the rate of diabetes was 4.75 per 1000 person‐year (PY) during the COVID‐19 pandemic (up to 31 March 2021), which was 32% lower (95% confidence interval [CI] 21%, 42%; p < 0.001) than pre‐pandemic (6.98 per 1000 PY for the period 1 April 2018 to 16 March 2020). In multivariable regression analysis, the first COVID‐19 state of emergency (first wave) was associated with an 87.3% (95% CI −98.6%, 13.9%; p = 0.07) reduction in diabetes diagnosis; this decreasing trend was sustained to the second COVID‐19 state of emergency and no substantial rebound (increase) was observed when the COVID‐19 state of emergency was relaxed. Conclusions: The COVID‐19 public health emergencies had a negative impact on diabetes diagnosis in Alberta. The reduction in diabetes diagnosis was likely due to province‐wide health service disruptions during the COVID‐19 pandemic. Systematic plans to close the post‐COVID‐19 diagnostic gap are required in diabetes to avoid substantial downstream sequelae of undiagnosed disease. [ABSTRACT FROM AUTHOR]

Background and purpose: Influenza vaccination is associated with a longer‐term protective effect against stroke; however, it has a short‐term inflammatory response which may increase short‐term risk of stroke. The aim was to investigate the association between influenza vaccination and short‐term risk of stroke in adults. Methods: Administrative data were obtained from the Alberta Health Care Insurance Plan for all adults in Alberta, Canada, from September 2009 to December 2018. The hazard of any stroke (acute ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage and transient ischaemic attack) within 3, 7, 14, 21 and 30 days of influenza vaccination compared to unexposed time was analysed using Andersen−Gill Cox models, with adjustment for age, sex, anticoagulant use, atrial fibrillation, chronic obstructive pulmonary disease, diabetes, hypertension, income quintile, and rural or urban home location. Results: In the entire cohort consisting of 4,141,209 adults (29,687,899 person‐years), 1,769,565 (42.7%) individuals received at least one vaccination. In total 38,126 stroke events were recorded with 1309 occurring within 30 days of a vaccination event. Influenza vaccination was associated with a significantly reduced hazard of stroke within 3 days (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.73–0.93), 7 days (HR 0.87, 95% CI 0.80–0.95), 14 days (HR 0.87, 95% CI 0.81–0.93), 21 days (HR 0.85, 95% CI 0.80–0.91) and 30 days (HR 0.66, 95% CI 0.65–0.68). Conclusions: An increased early risk associated with vaccination was not observed. The risk of stroke was reduced at all time points within 30 days after influenza vaccination. [ABSTRACT FROM AUTHOR]

Background: Fertility‐sparing surgery (FSS) is an alternative choice of young patients who have not completed their family planning and still have fertility needs. The aims of this study were to compare the outcomes of early‐stage epithelial ovarian cancer (EOC) patients undergoing FSS and radical comprehensive staging surgery (RCS), and the suitability of FSS. Methods: A total of 1297 patients aged between 20 and 44 years with newly diagnosed early‐stage EOC were recruited from the Taiwan Cancer Registry database between 2009 and 2017. Site‐specific surgery codes were used to distinguish patients in FSS group or RCS group. Cancer‐specific survival (CSS) was evaluated using Kaplan–Meier method with log‐rank test and Cox regression model. Results: There were 401 and 896 patients in FSS and RCS group. Patients in FSS group were with younger age and mostly had Stage I disease. In contrast, patients in RCS group were older. There were more Stage II, high‐grade (Grade 3) disease, and adjuvant chemotherapy in RCS group. Stage and tumor grade were two independent factors correlating with CSS and the type of surgery showed no effect on CSS (HR: 1.09, 95% CI: 0.66–1.77, p = 0.73) in multivariable analysis. In multivariable analysis, the clear cell carcinoma group who underwent FSS demonstrated better CSS compared to those in the RCS group (HR: 0.28, 95% CI: 0.06–0.82, p = 0.04). A total of 17 women who underwent FSS developed second malignancies of the uterine corpus or contralateral ovary. Conclusion: FSS can be a safe alternative procedure in selected young patients of Stage I EOC who have fertility desire. Endometrial biopsy before or during FSS and regular surveillance to detect recurrence are mandatory for ovarian cancer patients undergoing FSS. [ABSTRACT FROM AUTHOR]

Objective: Abnormal ankle-brachial index (ABI) determinations may be associated with an increased risk of incident strokes. However, the impact of previous strokes in this relationship is unknown. We estimated the role of previous strokes on the association between abnormal ABI determinations and incident stroke risk in community-dwelling older adults. Methods: Atahualpa residents aged ≥60 years received ABI determinations, cardiovascular risk factors assessment, and brain MRIs. ABIs were classified as abnormal if ≤0.9 or ≥1.4. Incident strokes were diagnosed by a certified neurologist with the aid of a post-event MRI. Poisson regression models were fitted to estimate stroke incidence rate ratio (IRR) according to categories of ABI. Results: Analysis included 389 participants (mean age: 68.2 ± 8.1 years). Eighty-six persons (22%) had abnormal ABI determinations. Incident strokes occurred in 38 (9.8%) individuals after a mean follow-up of 6.1 ± 1.9 years. Abnormal ABIs were associated with incident strokes in unadjusted analyses (p = 0.002) as well as in a Poisson regression model adjusted for demographics and clinical covariates (IRR: 2.57; 95% C.I.: 1.29–5.13), but not when the model was adjusted for neuroimaging covariates (IRR: 1.46; 95% C.I.: 0.67–3.20). Interaction models showed that having both abnormal ABI and non-lacunar strokes at baseline made the individual 9.7 times more likely to have an incident stroke (95% C.I.: 3.87–24.4). The risk was reduced to 2.2 (95% C.I.: 0.96–5.13) for those who only had an abnormal ABI. Conclusions: An abnormal ABI is associated with a doubling the risk of incident strokes, but its importance is superseded by history of non-lacunar strokes. [ABSTRACT FROM AUTHOR]

Background: Low muscle mass is associated with adverse health outcomes such as functional decline and all-cause mortality. This study investigated the relationship between the risk of low muscle mass and the training period and/or frequency of resistance training (RT). Methods: We included 126,339 participants (81,263 women) from nationwide cohorts in Korea. Low muscle mass was defined based on the fat-free mass index. To investigate the presence of an inverse dose–response relationship between RT levels and the risk of low muscle mass, the training period (months) and frequency (per week) of RT were used. Multiple logistic regression models were used to assess the risk of low muscle mass according to the RT levels. Results: Prevalence rates for low muscle mass in our study population were 21.27% and 6.92% in men and women, respectively. When compared with not performing RT, performing RT for 3–4 days/week and ≥5 days/week decreased the risk of low muscle mass by 22% and 27%, respectively, and performing RT for 12–23 months and ≥24 months decreased the risk by 19% and 41%, respectively. When simultaneously considering both training period and frequency, performing RT for either 3–4 days/week or ≥5 days/week was significantly related to risk reduction, provided that the training period was at least 1 year. Importantly, performing RT for more than 2 years resulted in an additional risk reduction. However, there was no additional effect of performing RT for ≥5 days/week compared to 3–4 days/week, regardless of whether the RT duration was 1–2 years or more than 2 years. Conclusions: Since performing RT for 5 days/week or more did not yield any additional effects on the risk of low muscle mass, performing RT for 3–4 days/week was sufficient to prevent low muscle mass. The effectiveness of this preventive measure can be further enhanced by engaging in long-term RT, specifically for more than 2 years. [ABSTRACT FROM AUTHOR]

Background: The adoption of direct oral anticoagulants (DOACs) has changed practice in prevention of stroke in atrial fibrillation (AF). We used Irish data national data on stroke and anticoagulation therapy over 9 years to investigate changes in anticoagulation practice and potential consequences on stroke prevalence and thrombolysis. Methods: AF, anticoagulation, thrombolysis, and stroke data from the Irish National Audit of Stroke (INAS) 2013–2021 were reviewed. The proportion of patients with ischemic stroke (IS) and intracerebral hemorrhage (IH) with known AF admitted on anticoagulation was determined. Effects on age distribution in the population and thrombolysis practice were assessed. Results: AF data were available on 34,630 of 35,241 individuals (98.3%) included in INAS; median age was 74 years and 56% were male. AF was found in 10,016 (28.9%, 9059 IS, 957 IH). 6313 had known AF prior to stroke (63.1%). The proportion all total IS due to AF decreased by 15.3% (31.3%−26.5%, chi-square = 24.6, p < 0.0001). The proportion of IH did not change significantly (21.6%–20.2%, chi-square = 1.8, p = 0.18). Over the 9 years, 3875 (38.6%) of the subjects with AF were recorded as receiving anticoagulants at admission. In 2013, 4.4% of AF-associated strokes were admitted on a DOAC and 21.4% on warfarin; by 2021, 44.1% were receiving a DOAC and 6.2% warfarin. There was a strong inverse correlation between the proportion of anticoagulated stroke patients and the total proportion of AF-associated strokes over time (r = −0.82, p = 0.006). In contrast, no correlation was found between increasing DOAC usage and IH (r = 0.14, p = 0.71). Increased anticoagulation usage correlated with a reduction in patients ⩾ 80 years (r = −0.83, p = 0.006) and also correlated with a relative reduction of 30.1% in subjects thrombolysed <4 h from onset (r = −0.89, p = 0.001) Conclusion: DOACs have led to increased use of anticoagulation, but warfarin use fell by two-thirds. There has been a reduction in the proportion of AF-associated IS without a noticeable increase in IH. Increased anticoagulation correlated with reduced numbers of strokes in those >80 years and in the proportion of patients thrombolysed. [ABSTRACT FROM AUTHOR]

Noonan syndrome is a group of diseases with a similar clinical picture, consisting of 16 diseases caused by mutations in 15 genes. According to the literature, approximately half of all cases are attributed to Noonan syndrome type 1, NSML, caused by mutations in the PTPN11 gene. We analyzed 456 unrelated probands using a gene panel NGS, and in 206 cases, the cause of the disease was identified. Approximately half of the cases (107) were caused by variants in the PTPN11 gene, including three previously undescribed variants, one of which was classified as VOUS, and the other two as LP causative complex alleles. Frequent variants of the PTPN11 gene characteristics for Russian patients were identified, accounting for more than 38% (c.922A>G p.Asn308Asp, c.417G>C p.Glu139Asp, c.1403C>T p.Thr468Met) of all cases with mutations in the PTPN11 gene. A comparative characterization of frequent variants of the PTPN11 gene in different populations is shown. The most common features of Noonan syndrome in the studied sample were facial dysmorphisms and cardiovascular system abnormalities. A lower representation of patients with growth delay was observed compared to previously described samples. [ABSTRACT FROM AUTHOR]

Aim: To examine the association between 1‐hour plasma glucose (PG) concentration and markers of non‐alcoholic fatty liver disease (NAFLD) assessed by transient elastography (TE). Methods: We performed TE in 107 metabolically well‐characterized non‐diabetic White individuals. Controlled attenuation parameter (CAP) was used to quantify liver steatosis, while liver stiffness marker (LS) was used to evaluate fibrosis. Results: Controlled attenuation parameter correlated significantly with 1‐hour PG (r = 0.301, P < 0.01), fasting insulin (r = 0.285, P < 0.01), 2‐hour insulin (r = 0.257, P < 0.02), homeostasis model assessment index of insulin resistance (r = 0.252, P < 0.01), high‐density lipoprotein cholesterol (r = −0.252, P < 0.02), body mass index (BMI; r = 0.248, P < 0.02) and age (r = 0.212, P < 0.03), after correction for age, sex and BMI. In a multivariable linear regression analysis, 1‐hour PG (β = 0.274, P = 0.008) and fasting insulin levels (β = 0.225, P = 0.029) were found to be independent predictors of CAP. After excluding subjects with prediabetes, 1‐hour PG was the sole predictor of CAP variation (β = 0.442, P < 0.001). In a logistic regression model, we observed that the group with 1‐hour PG ≥ 8.6 mmol/L (155 mg/dL) had a significantly higher risk of steatosis (odds ratio 3.98, 95% confidence interval 1.43‐11.13; P = 0.008) than individuals with 1‐hour PG < 8.6 mmol/L, after correction for potential confounders. No association was observed between 1‐hour PG and LS. Conclusion: Our data confirm that 1‐hour PG ≥ 8.6 mmol/L is associated with higher signs of NAFLD, even among individuals with normal glucose tolerance, categorized as low risk by canonical diagnostic standards. TE is a safe low‐impact approach that could be employed for stratifying the risk profile in these patients, with a high level of accuracy. [ABSTRACT FROM AUTHOR]