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To investigate longitudinal changes in peripapillary choroidal thickness (pCT) and retinal nerve fiber thickness (pRNFLT) in patients with Type 2 diabetes mellitus.This was a prospective observational cohort study. Patients with Type 2 diabetes mellitus without diabetic retinopathy (DR) at baseline were recruited, followed up for three years, and further divided into an incident DR group and a non-DR group according to the outcome. The pCT and pRNFLT were measured through swept-source optical coherence tomography at 1-year interval, and the mean rates of pCT and pRNFLT thinning were compared between the DR groups.A total of 682 patients (682 eyes) were included in the final analysis. After 3-years follow-up, 122 (17.89%) developed DR. Both pCT and pRNFLT progressively thinned (-2.37 [-2.80 to -1.95] µm/year; -0.40 [-0.55 to -0.25] µm/year, respectively, P0.05) and accelerated thinning was observed in the incident DR group. The rates of pCT thinning (-3.92 [-4.96 to -2.88] µm/year, -2.03 [-2.49 to -1.57] µm/year, respectively) and pRNFLT loss (-1.03 [-1.31 to -0.76] µm/year, -0.26 [-0.43 to -0.09] µm/year, respectively) in the incident DR group were 1.93 and 3.96 times faster than those in the non-DR group, respectively. In addition, pCT and pRNFLT thinning were negatively related in Type 2 diabetes mellitus population, and faster pCT thinning indicated slower pRNFLT loss.Patients with Type 2 diabetes mellitus were at a higher risk of developing DR when accelerated pCT and pRNFLT thinning were present, indicating that heavier choroidal damage and retinal neurodegeneration precede clinical DR. The pCT and pRNFLT have the potential to serve as novel sensitive biomarkers of preclinical and early DR.

Background: Retinal parameters could reflect systemic vascular changes. With the advances of deep learning technology, we have recently developed an algorithm to predict retinal age based on fundus images, which could be a novel biomarker for aging and mortality. Therefore, we aim to investigate associations of retinal age gap with arterial stiffness index and incident cardiovascular disease (CVD). Methods: A deep learning model was trained based on 19 200 fundus images of 11 052 participants without any medical history at baseline to predict the retinal age. Retinal age gap (retinal age predicted minus chronological age) was generated for the remaining 35 917 participants. Regression models were used to assess the association between retinal age gap and arterial stiffness index. Cox proportional hazards regression models and restricted cubic splines were used to explore the association between retinal age gap and incident CVD. Results: We found each 1-year increase in retinal age gap was associated with increased arterial stiffness index (β=0.002 [95% CI, 0.001–0.003]; P P =0.014). In the restricted cubic splines analysis, the risk of incident CVD increased significantly when retinal age gap reached 1.21 (hazard ratio=1.05 [95% CI, 1.00–1.10]; P -overall P -nonlinear=0.0681). Conclusions: We found that retinal age gap was significantly associated with arterial stiffness index and incident CVD events, supporting the potential of this novel biomarker in identifying individuals at high risk of future CVD events.

Purpose : The association between visual impairment (VI) and the risk of dementia has been poorly understood. We sought to investigate the VI-dementia relationship in the UK Biobank Study. Design : Prospective cohort study Methods : A total of 117,187 volunteers (aged 40-69 years) deemed free of dementia at baseline were included. Habitual distance visual acuity worse than 0.3 logMAR units in the better-seeing eye was used to define VI. The incident dementia was based on electronically linked hospital inpatient and death records. Results : During a median follow up of 5.96 years, the presence of VI was significantly associated with incident dementia (HR=1.78, 95% CI: 1.18-2.68, P=0.006). There was a clear trend between the severity of VI and the risk of dementia (P for trend=0.002). Conclusions : We found VI was associated with increased risk of dementia, with a progressively greater risk among those with worse visual acuity. Our findings suggested that visual impairment might be a modifiable risk factor for dementia and highlighted the potential value of VI elimination to delay the manifestation of dementia.

Background: Little is known about the association between macronutrient intake and incident dementia. Objective: To identify an optimal range of macronutrient intake associated with reduced risk of dementia. Methods: Our analysis included 93,389 adults aged 60–75 years from the UK Biobank. Diet was assessed using a web-based 24-h recall questionnaire between 2009–2012. Dementia was ascertained using hospital inpatient, death records, and self-reported data up to January 2021. We calculated a macronutrient score based on associations between an individual’s macronutrient intake and incident dementia. Results: During a median follow-up of 8.7 years, 1,171 incident dementia cases were documented. We found U-shape relationships for carbohydrate, fat, and protein intake with incident dementia. Compared to individuals with optimal carbohydrate intake, those with high intake (HR (95%CI): 1.48(1.15–1.91)) but not low intake (1.19(0.89–1.57)) had a higher risk of dementia. In the multivariable analysis, a low-fat intake (HR (95%CI): 1.42(1.11–1.82)) was associated with a higher risk of all-cause dementia. After adjustment for covariates, a high (HR (95%CI): 1.41(1.09–1.83)) but not low protein intake (1.22(0.94–1.57)) was associated with an increased risk of dementia. Individuals in quintiles 3–5 of optimal macronutrient score had a lower risk of dementia compared with those in quintile 1 (HR (95%CI): 0.76(0.64–0.91) for quintile 3, 0.71(0.60–0.85) for quintile 4, 0.74(0.61–0.91) for quintile 5). The association between macronutrient score and incident dementia was significant across subgroups of age, gender, education, and smoking. Conclusion: Moderate intakes of carbohydrate, fat, and protein were associated with the lowest risk of incident dementia.

Metabolic syndrome (MetS) is a clustering of cardiometabolic components, posing tremendous burdens in the aging society. Retinal age gap has been proposed as a robust biomarker associated with mortality and Parkinson's disease. Although MetS and chronic inflammation could accelerate the aging process and increase the risk of mortality, the association of the retinal age gap with MetS and inflammation has not been examined yet.Retinal age gap (retina-predicted age minus chronological age) was calculated using a deep learning model. MetS was defined as the presence of three or more of the following: central obesity, hypertension, dyslipidemia, hypertriglyceridemia, and hyperglycemia. Inflammation index was defined as a high-sensitivity C-reactive protein level above 3.0 mg/L. Logistic regression models were used to examine the associations of retinal age gaps with MetS and inflammation.We found that retinal age gap was significantly associated with MetS and inflammation. Specifically, compared to participants with retinal age gaps in the lowest quartile, the risk of MetS was significantly increased by 10% and 14% for participants with retinal age gaps in the third and fourth quartile (odds ratio [OR]:1.10; 95% confidence interval [CI], 1.01,1.21;, p = .030; OR: 1.14, 95% CI, 1.03,1.26; p = .012, respectively). Similar trends were identified for the risk of inflammation and combined MetS and inflammation.We found that retinal age gaps were significantly associated with MetS as well as inflammation. Given the noninvasive and cost-effective nature and the efficacy of the retinal age gap, it has great potential to be used as a screening tool for MetS in large populations.

We aimed to examine speed of movement and its interactive association with fatness to changes in cardiometabolic risk factors over one year in children. The analysis included 8345 children aged 6–13 years. Cardiometabolic risk score was computed by summing Z-scores of waist circumference, the average of systolic and diastolic blood pressure, fasting glucose, high-density lipoprotein cholesterol (multiplied by −1), and triglycerides. Both high baseline and improvement in speed of movement were associated with favourable changes in percent body fat, lipids, and cardiometabolic risk score. Percentages of the association between baseline speed of movement and changes in cardiometabolic risk score, triglycerides, and high-density lipoprotein cholesterol explained by baseline BMI were 24.6% (19.6–29.1%), 26.2% (19.7–31.1%), and 12.5% (9.6–15.4%), respectively. The corresponding number for percent body fat was 47.0% (40.4–54.1%), 43.3% (36.7–51.7%), and 29.8% (25.0–34.6%), respectively. Speed of movement mediated the association between fatness and cardiometabolic risk factors. Improved speed of movement was associated with a lower increase in blood pressure in obese children only. Speed of movement is a strong predictor of changes in cardiometabolic risk factors. Fatness and speed of movement are interactively associated with cardiometabolic risk factors. Speed of movement may attenuate the positive association between fatness and blood pressure.

Background: A few studies have linked dietary patterns and sleep to cognitive decline. Objective: To examine the independent and joint associations of dietary patterns and sleep with cognitive decline. Methods: Our analysis included 2,307 participants aged 55– 89 years at baseline from the China Health and Nutrition Survey. Dietary intake was assessed using weighing methods in combination with 24 h dietary recalls for three consecutive days. Exploratory factor analysis was applied to identify major dietary factors. Cognition was assessed in 1997, 2000, 2004, 2006, and 2015. Results: Five dietary patterns were identified: dairy-fruits-fast foods, grains-vegetables-pork, plant-based food, beans-mushroom, and beverages-nuts patterns. Beans-mushroom pattern and sleep duration of 8 h/day were defined as healthy habits. There was a positive association between the beans-mushroom pattern and change in the global cognitive Z-score over seven years (β (95% CI) for quintile 5 versus quintile 1:0.17 (0.05, 0.30)). Compared to individuals with sleep duration of 8 h/day, those with sleep duration of≤5 h/day (β (95% CI): – 0.23 (– 0.45, – 0.00)) or > 10 h/day (– 0.52 (– 0.73, – 0.32)) had a greater decrease in global cognitive Z-score. Compared to individuals with no healthy patterns, those with a healthy dietary pattern only (β (95% CI): 0.18 (0.08, 0.28)), healthy sleep pattern only (0.13 (0.04, 0.23), and both healthy dietary and sleep patterns (0.19 (0.08, 0.31)) had a relative increase in global cognitive Z-score. Conclusion: Our findings highlight the importance of involving both diet and sleep as intervention priorities for the potential prevention of cognitive decline.

Purpose To examine whether vision impairment and eye diseases are independently associated with memory decline in older adults. Design Cohort study. Methods We included 8,315 participants aged 50-94 years in China Health and Retirement Longitudinal Study (CHARLS) from China and 8,939 participants aged 50-95 years in Health and Retirement Study (HRS) from the United States in our analysis. Results During 4.0 years’ follow-up, the composite memory decreased by 0.16 points in CHARLS. During 3.9 years’ follow-up, the composite memory decreased by 0.51 in HRS. Distance vision impairment was inversely associated with an annual change in composite memory (β [95% CI]: –0.07 [–0.12, –0.01]) and immediate memory (–0.04 [–0.07, –0.02]) in CHARLS, and the corresponding values in HRS were –0.19 (–0.34, –0.05) and –0.07 (–0.13, –0.00), respectively. Near vision impairment was inversely associated with an annual change in delayed memory in CHARLS and composite memory, immediate memory, and delayed memory in HRS. In HRS, the association between distance vision impairment and memory decline was observed in individuals aged

Background Aberrant epigenetic modifications such as DNA methylation may contribute to the pathogenesis of DR. We aimed at elucidating the role of novel DNA methylation modifications in diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) using an extreme phenotypic design. Methods/results Two consecutive studies were conducted. A cross-sectional study using an extreme phenotypic design was conducted to identify rare methylation modifications that might contribute to DR pathogenesis. A 2-year longitudinal nested case–control study was conducted to validate the results and assess whether these novel methylation modifications could be used as biomarkers for predicting DR onset. A large number of differentially methylated CpG sites were identified in the cross-sectional study, and two (cg12869254 and cg04026387) corresponding to known genes were replicated in the longitudinal study. Higher methylation of cg12869254 significantly correlated with macular RNFL thinning in the superior and nasal subregions, and that of cg04026387 correlated with reduced deep capillary plexus VD in the superior and inferior subregions after adjusting for covariates. Conclusions Cg12869254 and cg04026387 hypermethylation may complement the known risk factors that contribute to the pathogenesis of DR and as novel biomarkers for disease prediction.

Background Plasma metabolomic profile is disturbed in dementia patients, but previous studies have discordant conclusions. Methods Circulating metabolomic data of 110,655 people in the UK Biobank study were measured with nuclear magnetic resonance technique, and incident dementia records were obtained from national health registers. The associations between plasma metabolites and dementia were estimated using Cox proportional hazard models. The 10-fold cross-validation elastic net regression models selected metabolites that predicted incident dementia, and a 10-year prediction model for dementia was constructed by multivariable logistic regression. The predictive values of the conventional risk model, the metabolites model, and the combined model were discriminated by comparison of area under the receiver operating characteristic curves (AUCs). Net reclassification improvement (NRI) was used to estimate the change of reclassification ability when adding metabolites into the conventional prediction model. Results Amongst 110,655 participants, the mean (standard deviation) age was 56.5 (8.1) years, and 51 186 (46.3%) were male. A total of 1439 (13.0%) developed dementia during a median follow-up of 12.2 years (interquartile range: 11.5–12.9 years). A total of 38 metabolites, including lipids and lipoproteins, ketone bodies, glycolysis-related metabolites, and amino acids, were found to be significantly associated with incident dementia. Adding selected metabolites (n=24) to the conventional dementia risk prediction model significantly improved the prediction for incident dementia (AUC: 0.824 versus 0.817, p =0.042) and reclassification ability (NRI = 4.97%, P = 0.009) for identifying high risk groups. Conclusions Our analysis identified various metabolomic biomarkers which were significantly associated with incident dementia. Metabolomic profiles also provided opportunities for dementia risk reclassification. These findings may help explain the biological mechanisms underlying dementia and improve dementia prediction.

Background Dual sensory impairment is affecting over 10% of older adults worldwide. However, the long-term effect of dual sensory impairment (DSI) on the risk of mortality remains controversial. We aim to investigate the impact of single or/and dual sensory impairment on the risk of mortality in a large population-based sample of the adult in the UK with 14-years of follow-up. Methods This population-based prospective cohort study included participants aged 40 and over with complete records of visual and hearing functions from the UK Biobank study. Measurements of visual and hearing functions were performed at baseline examinations between 2006 and 2010, and data on mortality was obtained by 2021. Dual sensory impairment was defined as concurrent visual and hearing impairments. Cox proportional hazards regression models were employed to evaluate the impact of sensory impairment (dual sensory impairment, single visual or hearing impairment) on the hazard of mortality. Results Of the 113,563 participants included in this study, the mean age (standard deviation) was 56.8 (8.09) years, and 61,849 (54.5%) were female. At baseline measurements, there were 733 (0.65%) participants with dual sensory impairment, 2,973 (2.62%) participants with single visual impairment, and 13,560 (11.94%) with single hearing impairment. After a follow-up period of 14 years (mean duration of 11 years), 5,992 (5.28%) participants died from all causes. Compared with no sensory impairment, dual sensory impairment was significantly associated with an estimated 44% higher hazard of mortality (hazard ratio: 1.44 [95% confidence interval, 1.11–1.88], p = 0.007) after multiple adjustments. Conclusions Individuals with dual sensory impairment were found to have an independently 44% higher hazard of mortality than those with neither sensory impairment. Timely intervention of sensory impairment and early prevention of its underlying causes should help to reduce the associated risk of mortality.

Using a geographical information system (GIS), we investigated the spatiotemporal evolution of a cataract surgery service and its association with socioeconomic factors and private insurance, based on 10-year real-world medical claim data in an Australian population. The data collected cover a decade (2007–2016) from the “45 and Up Study”. A total of 234,201 participants within the cataract surgery service were grouped into 88 Statistical Area Level 3 (SA3s) according to their residential postcodes in New South Wales Australia. We analyzed the spatiotemporal variations and geographical distribution inequality in cataract surgery incidence and its respect to socioeconomic status (SES) and private health insurance coverage by Spearman correlation analysis and Moran’s I test. Then these variations were intuitive displayed by six-quartile maps and a local indicator of spatial association (LISA) maps based on GIS. The average cumulative age-gender-standardized of the incidence of cataract surgery (ICS) was 8.85% (95% CI, 5.33–15.6). Spatial variation was significant (univariate Moran’s I = 0.45, P = 0.001) with incidence gradually decreasing from the coastal regions to the north-western inland regions, suggesting inequality in the cataract surgery service across the state of New South Wales. Notably, clustering of the low incidence areas had gradually disappeared over the decade, suggesting that the cataract surgery service has improved over time. Low scores on the “index of socioeconomic disadvantages” (IRSD) and high private health insurance coverage were significantly associated with a higher incidence of cataract surgery (bivariate Moran’s I = −0.13 and 0.23, P P = 0.02), which is displayed on the map visually and obviously. Spatiotemporal variations in the incidence of cataract surgery are significant, but the low incidence area had gradually disappeared over time. High socioeconomic status and private insurance contribute to a higher incidence of cataract surgery in Australia.

Objectives We aimed to develop machine learning models and evaluate their performance in predicting HIV and sexually transmitted infections (STIs) diagnosis based on a cohort of Australian men who have sex with men (MSM). Methods We collected clinical records of 21,273 Australian MSM during 2011–2017. We compared accuracies for predicting HIV and STIs (syphilis, gonorrhoea, chlamydia) diagnosis using four machine learning approaches against a multivariable logistic regression (MLR) model. Results Machine learning approaches consistently outperformed MLR. Gradient boosting machine (GBM) achieved the highest area under the receiver operator characteristic curve for HIV (76.3%) and STIs (syphilis, 85.8%; gonorrhoea, 75.5%; chlamydia, 68.0%), followed by extreme gradient boosting (71.1%, 82.2%, 70.3%, 66.4%), random forest (72.0%, 81.9%, 67.2%, 64.3%), deep learning (75.8%, 81.0%, 67.5%, 65.4%) and MLR (69.8%, 80.1%, 67.2%, 63.2%). GBM models demonstrated the ten greatest predictors collectively explained 62.7-73.6% of variations in predicting HIV/STIs. STIs symptoms, past syphilis infection, age, time living in Australia, frequency of condom use with casual male sexual partners during receptive anal sex and the number of casual male sexual partners in the past 12 months were most commonly identified predictors. Conclusions Machine learning approaches are advantageous over multivariable logistic regression models in predicting HIV/STIs diagnosis.

Background Little is known regarding life-course trajectories of important diseases. We aimed to identify diseases that were strongly associated with mortality and test temporal trajectories of these diseases before mortality. Methods Our analysis was based on UK Biobank. Diseases were identified using questionnaires, nurses’ interviews, or inpatient data. Mortality register data were used to identify mortality up to January 2021. The association between 60 individual diseases at baseline and in the life course and incident mortality was examined using Cox proportional regression models. Those diseases with great contribution to mortality were identified and disease trajectories in life course were then derived. Results During a median follow-up of 11.8 years, 31,373 individuals (median age at death (interquartile range): 70.7 (65.3–74.8) years, 59.4% male) died of all-cause mortality (with complete data on diagnosis date of disease), with 16,237 dying with cancer and 6702 with cardiovascular disease (CVD). We identified 37 diseases including cancers and heart diseases that were associated with an increased risk of mortality independent of other diseases (hazard ratio ranged from 1.09 to 7.77). Among those who died during follow-up, 2.2% did not have a diagnosis of any disease of interest and 90.1% were diagnosed with two or more diseases in their life course. Individuals who were diagnosed with more diseases in their life course were more likely to have longer longevity. Cancer was more likely to be diagnosed following hypertension, hypercholesterolemia, CVD, or digestive disorders and more likely to be diagnosed ahead of CVD, chronic kidney disease (CKD), or digestive disorders. CVD was more likely to be diagnosed following hypertension, hypercholesterolemia, or digestive disorders and more likely to be diagnosed ahead of cancer or CKD. Hypertension was more likely to precede other diseases, and CKD was more likely to be diagnosed as the last disease before more mortality. Conclusions There are significant interplays between cancer and CVD for mortality. Cancer and CVD were frequently clustered with hypertension, CKD, and digestive disorders with CKD highly being diagnosed as the last disease in the life course. Our findings underline the importance of health checks among middle-aged adults for the prevention of premature mortality.

PurposeTo assess the impact of retinopathy and systemic vascular comorbidities on the all-cause mortality in a representative U.S. sample.MethodsA total of 5703 participants (≥40 years old) from the 2005-2008 National Health and Nutrition Examination Survey. The Early Treatment Diabetic Retinopathy Study grading scale was used to evaluate the retinopathy status. Systemic vascular comorbidities included diabetes mellitus (DM), high blood pressure (HBP), chronic kidney disease (CKD) and cardiovascular disease (CVD). Time to death was calculated as the time from baseline to either the date of death or censoring (December 31st, 2015), whichever came first. Risks of mortality were estimated using Cox proportional hazards models after adjusting for confounders and vascular comorbidities.ResultsAfter a median follow-up of 8.33 years (IQR: 7.50-9.67 years), there were 949 (11.8%) deaths from all causes. After adjusting for confounders, the presence of retinopathy predicted higher all-cause mortality (hazard ratio (HR), 1.41; 95% confidence interval (CI), 1.08-1.83). The all-cause mortality among participants with both retinopathy and systemic vascular comorbidities including DM (HR, 1.72; 95% CI, 1.21-2.43), HBP (HR, 1.47; 95% CI, 1.03-2.10), CKD (HR, 1.73; 95% CI, 1.26-2.39) and CVD (HR, 1.92; 95% CI, 1.21-3.04) was significantly higher than that among those without either condition. When stratified by diabetic or hypertension status, the co-occurrence of retinopathy and CKD or CVD further increased the all-cause mortality compared to those without either condition.ConclusionsThe co-occurrence of retinopathy and systemic vascular conditions predicted a further increase in the risk of mortality. More extensive vascular risk factor assessment and management are needed to detect the burden of vascular pathologies and improve long-term survival in individuals with retinopathy.

ObjectivesTo investigate the spatial distribution of 10-year incidence of diagnosed type 2 diabetes mellitus (T2DM) and its association with obesity and physical inactivity at a reginal level breakdown.MethodsDemographic, behavioral, medical and pharmaceutical and diagnosed T2DM incidence data were collected from a cohort of 232,064 participants who were free of diabetes at enrolment in the 45 and Up Study, conducted in the state of New South Wales (NSW), Australia. We examined the geographical trend and correlation between obesity prevalence, physical inactivity rate and age-and-gender-adjusted cumulative incidence of T2DM, aggregated based on geographical regions.ResultThe T2DM incidence, prevalence of obesity and physical inactivity rate at baseline were 6.32%, 20.24%, and 18.7%, respectively. The spatial variation of T2DM incidence was significant (Moran’s I=0.52; pConclusionThe spatial distribution of T2DM incidence is significantly associated with the geographical prevalence of obesity and physical inactivity rate. Regional campaigns advocating the importance of physical activities in response to the alarming T2DM epidemic should be promoted.

Little is known about whether the association of hypertension with brain volume and dementia is modified by an individual’s age at their diagnosis of hypertension. Our analysis was based on the UK Biobank with baseline data collected between 2006 and 2010. Brain magnetic resonance imaging was used to measure brain volumes between 2014 and 2019. Dementia was ascertained using hospital inpatient, mortality, and self-reported data until 2021. We randomly selected a control participant for each hypertensive participant stratified by hypertension diagnosis age using propensity score. The cohort comprised 11 399 individuals with hypertension and 11 399 controls for the brain volume analysis and 124 053 individuals with hypertension and 124 053 controls for the dementia analysis. Individuals with hypertension diagnosed at ages

ImportanceVision loss and depression are common conditions with major health implications. However, mechanisms of the association of visual health (across the full acuity spectrum) with depression remain unclear.ObjectiveTo characterize the association between visual health and depression and investigate the association between depression and brain microstructure and macrostructure in subgroups divided by visual acuity.Design, Setting, and ParticipantsIn the UK Biobank Study cohort, 114 583 volunteers were included at baseline from March to June 2006 to July 2010. Habitual distance visual acuity was examined using the logarithm of the minimum angle of resolution (LogMAR) characters. Depression was identified based on Patient Health Questionnaire (PHQ) or through an interview-based psychiatric diagnosis. Subgroup participants completed multimodal magnetic resonance imaging (MRI) of the brain and PHQ evaluation during the imaging visit after 2014. Data were analyzed from May 5 to August 9, 2022.Main Outcomes and MeasuresDepression, depressive symptoms, and imaging-derived phenotypes from T1-weighted and diffusion MRI.ResultsOf the 114 583 participants from the UK Biobank Study, 62 401 (54.5%) were women, and the mean (SD) age was 56.8 (8.1) years (range, 39-72 years). A 1-line worse visual acuity (0.1 LogMAR increase) was associated with 5% higher odds of depression (odds ratio, 1.05 [95% CI, 1.04-1.07]) after adjustment for age, sex, race and ethnicity, Townsend index, educational qualifications, smoking, alcohol consumption, obesity, physical activity, history of hypertension, diabetes, hyperlipidemia, and family history of depression. Of the 7844 participants eligible for MRI analysis, there were linear associations between PHQ score and the left volume of gray matter in supracalcarine cortex (coefficient, 7.61 [95% CI, 3.90-11.31]) and mean isotropic volume fraction (ISOVF) in the right fornix (cres) and/or stria terminalis (coefficient, 0.003 [95% CI, 0.001-0.004]) after correction for multiple comparison. In addition, their association could be moderated by visual acuity, whereby increased PHQ score was associated with higher ISOVF levels only among those with poorer visual acuity (P = .02 for interaction).Conclusions and RelevanceThis study suggests an association between visual health and depression and that the diffusion characteristic of ISOVF in the fornix (cres) and/or stria terminalis is associated with depressive symptoms in participants with poorer visual acuity.

Introduction retinal age derived from fundus images using deep learning has been verified as a novel biomarker of ageing. We aim to investigate the association between retinal age gap (retinal age–chronological age) and incident Parkinson’s disease (PD). Methods a deep learning (DL) model trained on 19,200 fundus images of 11,052 chronic disease-free participants was used to predict retinal age. Retinal age gap was generated by the trained DL model for the remaining 35,834 participants free of PD at the baseline assessment. Cox proportional hazards regression models were utilised to investigate the association between retinal age gap and incident PD. Multivariable logistic model was applied for prediction of 5-year PD risk and area under the receiver operator characteristic curves (AUC) was used to estimate the predictive value. Results a total of 35,834 participants (56.7 ± 8.04 years, 55.7% female) free of PD at baseline were included in the present analysis. After adjustment of confounding factors, 1-year increase in retinal age gap was associated with a 10% increase in risk of PD (hazard ratio [HR] = 1.10, 95% confidence interval [CI]: 1.01–1.20, P = 0.023). Compared with the lowest quartile of the retinal age gap, the risk of PD was significantly increased in the third and fourth quartiles (HR = 2.66, 95% CI: 1.13–6.22, P = 0.024; HR = 4.86, 95% CI: 1.59–14.8, P = 0.005, respectively). The predictive value of retinal age and established risk factors for 5-year PD risk were comparable (AUC = 0.708 and 0.717, P = 0.821). Conclusion retinal age gap demonstrated a potential for identifying individuals at a high risk of developing future PD.

OBJECTIVES: To investigate if smoking was related to the risk of cataract surgery in diabetic patients. METHODS: A total of 9578 diabetic participants aged 45–65 years were enrolled from the 45 and Up Study, the largest population-based cohort study in Australia. Baseline questionnaire data were linked to the Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) database, which were both available from 2004 to 2016. Cataract surgery was determined according to the MBS. Smoking status were assessed by questionnaire. Cox regression was used to evaluate the association between smoking and incidence of cataract surgery during the follow-up. RESULTS: During a mean follow-up of 8.4 years, 995 participants underwent cataract surgery with a corresponding incidence of 12.4 cases per 1000 person-years. In all, 10.8% of participants were current smokers at baseline, 38.7% were former smokers, and 50.5% were never smokers. The incidence of cataract surgery was non-significantly higher in never-smoker compared to former or current smokers. Regression analysis showed no significant difference in cataract surgical risk among former, current, and never smokers. In addition, neither time since quitting of smoking nor age at quitting was associated with the risk of cataract surgery, although there was a marginally significant trend in a lower risk of cataract surgery with longer smoking cessation time for participant with normal weight (P for trend = 0.05). CONCLUSIONS: Despite that smoking was found to be related to the cataract and cataract surgery in the general population, we did not find any association between smoking and cataract surgery in diabetic patients.

IMPORTANCE: The rate and determinants of persistence to topical glaucoma medications are important for identifying patients at high risk of discontinuing medications and designing targeted approaches to improve persistence. BACKGROUND: To evaluate the rate and determinants of persistence to topical glaucoma medications among middle-aged and older Australian adults. DESIGN: Population-based cohort study. PARTICIPANTS: Participants in need of persistent topical glaucoma medications in the 45 and Up Study. METHODS: The 45 and Up Study is a large-scale population-based cohort study. Participants were classified as needing persistent topical glaucoma medications if at least three claims with related prescriptions were recorded. Persistence was defined as topical glaucoma medications were filled within 90 days. MAIN OUTCOME MEASURES: The rates and determinants of medication persistence at 2-year follow-up. RESULTS: A total of 12 899 patients requiring persistent topical glaucoma medications were identified. Among them, 9019 (69.9%) had persisted with their glaucoma medications for at least 2 years. Multiple logistic regression analysis documented significant effects of patient-related factors (gender, socioeconomic status, language spoken at home, lifestyle and comorbidities) and drug-related factors (total number and drug class) on the persistence rate. Those most at risk groups of non-persistence were those patients living in remote areas (odds ratio, OR: 0.59, 95% confidence interval, CI: 0.37-0.92), having family income over 70 000 AUD/year (OR: 0.53, 95% CI: 0.45-0.62), speaking other languages at home (OR: 0.61, 95% CI: 0.53-0.68), and using cholinergic classes of medications (OR: 0.55, 95% CI: 0.38-0.79). CONCLUSIONS AND RELEVANCE: Our data has shown a medium level of persistence to topical glaucoma medication among middle-aged and older Australian adults. However, efforts are still needed to improve the rate of persistence.

Background/aimsTo evaluate the associations of dietary consumption with the 10-year incidence of diabetic retinopathy (DR) progression in working-aged Australians with diabetes.MethodsWe obtained longitudinal data of all diabetic subjects aged 45–65 years from the baseline of the 45 and Up Study and linked this data with Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme claims until 2016. Retinal photocoagulation (RPC), as determined based on the MBS data, was used as a proxy measure of DR progression. Dietary measurements were assessed via self-reported consumption of meat, dairy products, whole-meal bread, breakfast cereal, vegetables, fruit and fruit juice using a self-administered questionnaire at baseline. Cox regression was used to assess the association between dietary consumption and incident RPC during the follow-up period.ResultsA total of 8122 participants were included in the current analysis with a mean age of 57.2±5.2 years. During a mean follow-up of 8.6 years, 314 participants (3.8% of baseline) received RPC. Higher consumption of cheese and whole-meal bread was associated with a lower risk of incident RPC, with the HRs of the highest quartiles versus the lowest being 0.58 (95% CI 0.41 to 0.83; test for trend, p=0.007) and 0.64 (0.46 to 0.89; p=0.04), respectively. Body mass index, insulin treatment and gender were significant modifiers for the association between cheese/whole-meal bread and RPC.ConclusionConsumption of cheese and whole-meal bread could reduce the risk of DR progression among the working-aged Australian population with diabetes.

To investigate the association between outdoor time and the risk of cataract surgery in a large Australian population.This was a population-based prospective cohort study with 137,133 participants 45 to 65 years of age and without prior history of cataract surgery from the 45 and Up Study. Outdoor hours per day on weekdays and weekends, as well as tanning with repeated sun exposure, were assessed by a self-administered baseline questionnaire. Cataract surgery events were confirmed by the Medicare Benefits Schedule from baseline until the end of follow-up in 2016.During a mean follow-up of 9 years, 14,338 participants received cataract surgery with a corresponding incidence of 10.5%. Multiple Cox regression analysis showed that more outdoor hours on weekends (P trend0.001) and the ability to get tanned by repeated sun exposure (P trend = 0.041) were significantly associated with a lower risk of cataract surgery, whereas more outdoor hours on weekdays were nominally significantly associated (P trend = 0.055). Participants who spent 10+ hours outdoors on weekends had 9% decreased risk compared with those who spent ≤2 hours outdoors. In addition, compared to participants who got very tanned by repeated sun exposure, those less likely to get tanned had a 5% to 7% increased risk of cataract surgery.In this large Australian cohort 45 to 65 years of age, more outdoor time and ease of tanning with sun exposure were associated with a lower incidence of cataract surgery.With proper sun protection, more outdoor time may lead to a lower risk of severe cataracts requiring surgery.

To examine the impact of diet on the incidence of cataract surgery among the working-aged diabetic population in Australia.This cohort study was conducted among 8,752 participants with diabetes aged 45-65 years who were recruited to the 45 and Up Study from 2006 to 2016. The data was linked to the Medicare Benefits Schedule to obtain data on cataract surgery. Diabetes was defined as self-reported on questionnaire or diabetes medication history based on Pharmaceutical Benefits Scheme. Diet was assessed at baseline, using a self-administered questionnaire and healthy diet scores were calculated based on Australian Dietary Guidelines. Cox regression was used to evaluate the association between diet and the incidence of cataract surgery during the follow-up.During a mean follow-up of 8.4 years (73,431 person-years), 914 diabetic participants underwent cataract surgery with a corresponding rate of 12.4 cases per 1,000 person-years. After adjusting for age and gender, the hazard ratios (HR) of cataract surgery for the highest compared to the lowest intake quintile of red meat and poultry were 1.24 (95% CI, 1.00-1.55) and 1.24 (95% CI, 1.02-1.51), respectively. Further adjustment for demographic, lifestyle and dietary factors resulted in no significant difference between cataract surgery risk and healthy diet scores or specific diet groups. In gender-stratified analyses, increasing consumption of red meat (HR for highest versus lowest quintile, 1.39; 95% CI, 1.00-1.93; P for trend = 0.01) and poultry (HR for highest versus lowest quintile, 1.40; 95% CI, 1.05-1.87; P for trend = 0.01) were associated with a higher risk of cataract surgery in women after adjustment of age, gender, income, education level, body mass index, hypertension, cardiovascular disease, family history of diabetes, diabetes duration, insulin use, lifestyle, and other dietary factors.Higher consumption of red meat and poultry is related to an elevated risk of cataract surgery in the working-aged female population with diabetes.

Background: Epithelial ovarian cancer (EOC) has the lowest survival rate among female reproductive cancers present with symptoms of aggressive malignancies, poor prognosis, drug resistance and postoperative recurrence. The majority of patients with EOC are diagnosed at an advanced stage due to the therapeutic challenges including lack of early diagnosis and effective therapeutic targets for EOC.Methods: Pan-cancer analyses were performed to explore the features of Forkhead box (FOX) A1 (FOXA1) using data from TCGA and GTEx database. R package “clusterprofiler” was used to perform the enrichment analysis of FOXA1 in EOC. Data downloaded from Drug Sensitivity in Cancer (GDSC) database were used to evaluate the association between FOXA1 and anti-tumor drug sensitivity. In experimental verification, FOXA1 expression was detected using qRT-PCR and Western blot assays. Western blot, immunofluorescence staining and transwell assays were used to assess the influence of FOXA1 silencing on epithelial-mesenchymal transition (EMT) of EOC cellsResults: We found that FOXA1 was highly expressed in EOC and predicted poorer survival of EOC patients. We observed that FOXA1 expression was positively correlated EMT related pathways. Through experimental verification, we found the underlying function of FOXA1 to promote EMT in ovarian cancers. Results from western blot, immunofluorescence staining and transwell assays showed that FOXA1 silencing impeded the progression of EMT and invasiveness of the cancer cells. Furthermore, CCK-8 and invasion assays suggested that siRNA-FOXA1 attenuated the ability of cancer cells to metastasize and proliferate. Dual-luciferase reporter assays confirmed the binding activity of FOXA1 to the promoter of connective tissue growth factor (CTGF). In addition, we found that FOXA1 was closely correlated immunosuppressive microenvironment of EOC. High FOXA1 expression may contribute to resistance of many anti-cancer drugs.Conclusions: Our results predict and validate the function of FOXA1 in promoting EMT and the progression of disease in EOC. Targeting FOXA1 may improve the sensitivity of EOC treatment.

Background/aimsTo investigate the feasibility and accuracy of using machine learning (ML) techniques on self-reported questionnaire data to predict the 10-year risk of cataract surgery, and to identify meaningful predictors of cataract surgery in middle-aged and older Australians.MethodsBaseline information regarding demographic, socioeconomic, medical history and family history, lifestyle, dietary and self-rated health status were collected as risk factors. Cataract surgery events were confirmed by the Medicare Benefits Schedule Claims dataset. Three ML algorithms (random forests [RF], gradient boosting machine and deep learning) and one traditional regression algorithm (logistic model) were compared on the accuracy of their predictions for the risk of cataract surgery. The performance was assessed using 10-fold cross-validation. The main outcome measures were areas under the receiver operating characteristic curves (AUCs).ResultsIn total, 207 573 participants, aged 45 years and above without a history of cataract surgery at baseline, were recruited from the 45 and Up Study. The performance of gradient boosting machine (AUC 0.790, 95% CI 0.785 to 0.795), RF (AUC 0.785, 95% CI 0.780 to 0.790) and deep learning (AUC 0.781, 95% CI 0.775 to 61 0.786) were robust and outperformed the traditional logistic regression method (AUC 0.767, 95% CI 0.762 to 0.773, all pConclusionsThe study demonstrated that ML modelling was able to reasonably accurately predict the 10-year risk of cataract surgery based on questionnaire data alone and was marginally superior to the conventional logistic model.

Childhood hypertension has increasingly become a public health problem globally. However, limited literature research examined the effect of comprehensive interventions including nutrition education and physical activity on blood pressure among children. A total of 6764 children aged 7&ndash, 13 years were analyzed based on a multicenter randomized controlled trial for comprehensive interventions in 30 primary schools in China to evaluate the effects on blood pressure, which lasted for two semesters. The standards used for the diagnosis of high blood pressure were the cut-off points based on age and sex for Chinese children. Compared with the control group, the intervention effects were &minus, 0.5 mm Hg (95% confidence interval (CI): &minus, 1.1, 0, p = 0.064) for diastolic blood pressure and &minus, 0.9 mmHg (95% CI: &minus, 1.5, &minus, 0.3, p = 0.005) for systolic blood pressure. For the incidence of high blood pressure, the changes were &minus, 1.4% in the intervention group and 0.4% in the control group (1.8% difference between the two groups, p = 0.015) after trial. The school-based comprehensive interventions appeared to have moderate effects on high blood pressure prevention among children in China.

This study aimed to examine whether pulmonary function and cognition are independently associated at multiple time points. We included 8264 participants (49.9% women) aged 50–94 years at baseline from the China Health and Retirement Longitudinal Study in our analysis. Participants were enrolled in 2011 and followed up in 2013 and 2015. Cognitive function was assessed through a face-to-face interview in each survey. Pulmonary function was assessed via peak expiratory flow. Pulmonary function and cognitive function decreased significantly with age in both genders. Individuals in quintile 5 of pulmonary function had a relative increase in immediate memory (β [95% CI]: 0.19 [0.09, 0.30]) and delayed memory (0.16 [0.04, 0.28]) during follow-up compared with those in quintile 1. In the repeated-measures analysis, each standard deviation increment of pulmonary function was associated with a 0.44 (95% CI: 0.34, 0.53), 0.12 (0.09, 0.15), 0.12 (0.08, 0.16), 0.08 (0.06, 0.11), and 0.10 (0.07, 0.14) higher increase in global cognitive score, immediate memory, delayed memory, orientation, and subtraction calculation, respectively. The inverse association between pulmonary function and cognitive decline during follow-up was more evident in women (p for interaction = .0333), low-educated individuals (p for interaction = .0002), or never smokers (p for interaction = .0412). In conclusion, higher baseline pulmonary function was independently associated with a lower rate of cognitive decline in older adults. The positive association between pulmonary function and cognition was stronger in women, lower-educated individuals, or never smokers.

Fc fragment of IgG-binding protein (FCGBP) is differentially expressed in various tumors. However, the correlation between FCGBP and immune cell infiltration in ovarian cancer remains unclear. FCGBP expression was analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data, and the ovarian cancer expression profile was analyzed using the Gene Expression Omnibus database. The clinical prognostic value of FCGBP was evaluated using clinical survival data from TCGA. Enrichment analysis of FCGBP was performed using the R package clusterProfiler. Based on known immune cell infiltration scores for samples found in TCGA, we analyzed the association between immune cell infiltration level and FCGBP expression. FCGBP was highly expressed and associated with poorer overall survival (p = 0.00051) and disease-specific survival (p = 0.0012) in ovarian cancer and other tumors. Additionally, high FCGBP expression correlated significantly with immune-related gene sets, including those involved in chemokine signaling pathways and innate and adaptive immunity. Further analysis showed that M2 macrophage infiltration increased and M1 macrophage infiltration decreased in tissues with high FCGBP expression. Our study suggests that FCGBP contributes to M2 macrophage polarization by acting as an oncogene in ovarian cancer. FCGBP may represent a clinically helpful biomarker for predicting overall survival of ovarian cancer patients.

PURPOSE: To investigate the geographic variation in the cumulative incidence of private cataract surgery (PCS) and its association with remoteness, socioeconomic, and private health insurance coverage indexes in a large Australian population. METHODS: A prospective population-based study of 266,896 Australian adults living in New South Wales (NSW) aged 45 years older and over were enrolled in the 45 and Up Study. PCS was identified using Medicare claims data. Participants were assigned to a Statistical Area Level 3 (SA3) based on residential postcode in NSW. Cumulative incidence of PCS (number of surgery per 100,000 population from 2006 to 2016) among 89 SA3s was calculated and standardized to the baseline population. Remoteness and socioeconomic deprivation was derived from Australian Bureau of Statistics (ABS). Private health insurance coverage rates were obtained from the baseline interview. RESULTS: A total of 257,237 participants with complete data were included in the current analysis. During the study period, a total of 67,707 cataract surgeries were performed among 39,744 participants. Cumulative incidence of PCS varied from 14,897 to 37,314 per 100,000 across 89 SA3s. Multivariable adjusted regression models showed that remoteness index and private health insurance coverage rates were independently associated with cumulative incidence of PCS (all P

Background: Findings for associations between cardiorespiratory fitness (CRF) and cardiometabolic risk (CMR) factors are inconsistent, and the interactive association between CRF and fatness with CMR factors is unclear in children. Our study aimed to examine whether CRF and fatness are independently and interactively associated with CMR factors.Methods: We included 5,869 children aged 6–13 years in the analysis. Physical examinations, blood tests, and CRF were measured at baseline and 1 year later. Cardiometabolic risk score (CMRS) was computed by summing Z scores of waist circumference (WC), averaged systolic and diastolic blood pressure, glucose, high-density lipoprotein cholesterol (HDL-C, multiplied by −1), and triglycerides.Results: There was a high correlation between fatness and CRF in both boys and girls. High baseline CRF was independently associated with favorable changes in CMRS, BMI, WC, percent body fat (PBF), total cholesterol, LDL-C, and HDL-C (all P < 0.025). Improved CRF was independently associated with favorable changes in CMRS, BMI, WC, PBF, total cholesterol, LDL-C, HDL-C, triglycerides, and fasting glucose (all P < 0.0321). Baseline BMI was positively associated with changes in CMRS, WC, blood pressure, triglycerides, insulin, and HOMA-IR (all P < 0.0462). Low PBF at baseline was associated with favorable changes in CMRS, BMI, WC, blood pressure, HDL-C, triglycerides, insulin, and HOMA-IR (all P < 0.0423). The percentage of the total effect of baseline CRF on changes in CMRS, triglycerides, HDL-C, PBF, and WC mediated by baseline BMI was 66.0, 61.6, 40.3, 20.7, and 9.2%, respectively. Baseline CRF was a significant mediator for the association between baseline BMI and changes in CMRS (mediated by 4.3%), triglycerides (5.1%), and HDL-C (12.0%). An inverse association was found between baseline CRF and CMRS in children with high baseline BMI/PBF only. Improved CRF was associated with decreased BMI and WC in children with low baseline CRF.Conclusions: Fatness and CRF are each independently associated with changes in CMR factors. Fatness is a major mediator for the association between CRF and CMR factors, whereas the association between fatness and CMR factors is also mediated by CRF. The beneficial effect of high CRF on CMR factors was more evident in obese or unfit children.

Although socioeconomic, behavioural, psychological, and biological factors have been individually linked to multimorbidity, data on the importance of these factors are limited. Our study aimed to determine the leading predictors for multimorbidity of chronic conditions in middle-aged Australian adults using machine learning methods. We included 53,867 participants aged 45-64 years from the 45 and Up Study who were free of eleven predefined chronic conditions at baseline (2006-2009) in the analysis. Incident multimorbidity was defined by the co-existence of ≥2, ≥3, or ≥ 4 conditions during follow-up until December 31, 2016. The five leading predictors for multimorbidity in men were age (7.2-20.5% of total variance), body mass index (6.5-15.4%), smoking (4.0-8.3%), chicken intake (3.6-7.5%), and red meat intake (4.6-6.3%) across the three definitions. Leading predictors varied across the three definitions in women, but the four common ones were body mass index (6.3-20.1%), age (6.2-16.4%), chicken intake (4.1-8.3%), and red meat intake (4.2-4.7%). The ten leading modifiable health factors accounted for 39.4-46.1% of total variance across the three definitions. Men with 6-10 health factors had 46-54% lower risks for multimorbidity compared with those reporting ≤2. The corresponding percentage for women was 45-52%. Non-behavioural factors including psychological distress, low education and income and high relative economic disadvantage were among the leading risk factors for multimorbidity. In conclusion, modifications on behavioural factors including diets, physical activity, smoking, alcohol consumption may reduce the risk of multimorbidity in middle-aged adults, whereas individuals with low socioeconomic status or psychological distress are at the highest priority for intervention.

The clustering of diet quality, physical activity, and sleep and its association with cardiometabolic risk (CMR) factors remains to be explored. We included 5315 children aged 6&ndash, 13 years in the analysis. CMR score (CMRS) was computed by summing Z-scores of waist circumference, an average of systolic and diastolic blood pressure, fasting glucose, high-density lipoprotein cholesterol (multiplying by &minus, 1), and triglycerides. Low diet quality and low cardiorespiratory fitness (CRF) were more likely to be seen in a pair, but low diet quality was less likely to be clustered with unhealthy sleep patterns. Low diet quality, low CRF, and unhealthy sleep pattern was associated with a 0.63, 0.53, and 0.25 standard deviation (SD) higher increase in CMRS, respectively. Compared to children with no unhealthy factor (&minus, 0.79 SD), those with &ge, 1 unhealthy factor had a higher increase (&minus, 0.20 to 0.59 SD) in CMRS. A low diet quality-unhealthy sleep pattern resulted in the highest increase in CMRS, blood pressure, and triglycerides. A low diet quality&ndash, low CRF-unhealthy sleep pattern resulted in the highest increase in fatness and fasting glucose. Unhealthy factor cluster patterns are complex, however, their positive associations with changes in CMR factors are consistently significant in children. Some specific patterns are more harmful than others for cardiometabolic health.

We examined whether energy and macronutrient intake from different meals was associated with changes in cardiometabolic risk (CMR) factors in children. CMR score (CMRS) was computed by summing Z-scores of waist circumference, the average of systolic and diastolic blood pressure, fasting glucose, high-density lipoprotein cholesterol (multiplying by &minus, 1), and triglycerides. We included 5517 children aged 6&ndash, 13 years from six major cities in China. Five meal patterns were identified according to energy intake: balanced, breakfast dominant, lunch dominant, dinner dominant, and snack dominant patterns. These patterns were not significantly associated with changes in CMR factors. Carbohydrate intake (% energy) at lunch was positively associated with the change in CMRS (beta coefficient (95% CI): (0.777 (0.509, 1.046) in quintile 5 versus quintile 1). A positive association between carbohydrate intake at dinner and change in CMRS was observed. High protein intake at both lunch and dinner was associated with a favorable change in CMRS. Moderate fat intake at lunch was associated with a lower increase in CMRS. Meal patterns driven by energy were not significantly associated with CMR factors, however, a low carbohydrate-high protein-moderate fat lunch and low carbohydrate-high protein dinner were associated with favorable changes in CMRS in children.

Background Identifying leading dietary determinants for cardiometabolic risk (CMR) factors is urgent for prioritizing interventions in children. We aimed to identify leading dietary determinants for the change in CMR and create a healthy diet score (HDS) to predict CMR in children. Methods We included 5676 children aged 6–13 years in the final analysis with physical examinations, blood tests, and diets assessed at baseline and one year later. CMR score (CMRS) was computed by summing Z-scores of waist circumference, an average of systolic and diastolic blood pressure (SBP and DBP), fasting glucose, high-density lipoprotein cholesterol (HDL-C, multiplying by − 1), and triglycerides. Machine learning was used to identify leading dietary determinants for CMR and an HDS was then computed. Results The nine leading predictors for CMRS were refined grains, seafood, fried foods, sugar-sweetened beverages, wheat, red meat other than pork, rice, fungi and algae, and roots and tubers with the contribution ranging from 3.9 to 19.6% of the total variance. Diets high in seafood, rice, and red meat other than pork but low in other six food groups were associated with a favorable change in CMRS. The HDS was computed based on these nine dietary factors. Children with HDS ≥8 had a higher decrease in CMRS (β (95% CI): − 1.02 (− 1.31, − 0.73)), BMI (− 0.08 (− 0.16, − 0.00)), SBP (− 0.46 (− 0.58, − 0.34)), DBP (− 0.46 (− 0.58, − 0.34)), mean arterial pressure (− 0.50 (− 0.62, − 0.38)), fasting glucose (− 0.22 (− 0.32, − 0.11)), insulin (− 0.52 (− 0.71, − 0.32)), and HOMA-IR (− 0.55 (− 0.73, − 0.36)) compared to those with HDS ≦3. Improved HDS during follow-up was associated with favorable changes in CMRS, BMI, percent body fat, SBP, DBP, mean arterial pressure, HDL-C, fasting glucose, insulin, and HOMA-IR. Conclusion Diets high in seafood, rice, and red meat other than pork and low in refined grains, fried foods, sugar-sweetened beverages, and wheat are leading healthy dietary factors for metabolic health in children. HDS is strongly predictive of CMR factors.

AimTo investigate the association between physical activity (PA) and incidence of cataract surgery among patients with diabetes.MethodsWe obtained data from all diabetic subjects aged 45-65 years from the baseline of the prospective 45 and Up Study from 2006 to 2009 and linked to the Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) until 2016. Diabetes was defined as self-reported on questionnaire or diabetes medication history based on PBS. Cataract surgery was determined based on the MBS, and metabolic equivalent intensity level number of PA sessions per week was used to assess PA. Cox regression was used to assess the association between baseline PA and cataract surgery during the follow-up.ResultsA total of 9113 diabetic participants in the 45 and Up Study were included in the current analysis with a mean age of 57.3±5.2 years (43.6% female). During a mean follow-up of 8.8 years, 950 participants (10.4% of baseline) received cataract surgery with a corresponding incidence of 12.4/1000 person-years. Cox regression analysis showed that people with less PA (p=0.01), older age (pConclusionsMore vigorous PA was independently associated with a reduced risk of cataract surgery in working-aged patients with diabetes.

Purpose To examine the association between adiposity by differing measures and incident cataract and identify important factors contributing to the association. Methods Our analysis included 153,139 adults from the UK Biobank, aged 40 to 70 years at baseline (2006–2010). Cataract was ascertained using hospital inpatient, and self-reported data until the early of 2021. Anthropometric measures, body fat percentage, and glycosylated hemoglobin (HbA1c) were measured at baseline. Results During a median follow-up of 10.9 years, 15,255 cases of incident cataract were documented. HbA1c was an important contributor to the association between obesity and incident cataract. Obesity; defined by body mass index was associated with an increased risk of cataract (hazard ratio [HR], 1.21 95% confidence interval [CI], 1.16–1.26), and this association was attenuated but remained significant after additional adjustment for HbA1c (HR, 1.05; 95% CI, 1.00–1.10). Similar results were observed for obesity defined by waist circumference or waist-to-hip ratio. Obesity defined by fat percentage was associated with an increased risk of cataract before but not after adjustment for covariates. The association between obesity defined by body mass index and incident cataract was positively significant in individuals with normal HbA1c (HR, 1.07; 95% CI, 1.02–1.13), but inversely significant in those with prediabetes (HR, 0.80; 95% CI, 0.67–0.96) or diabetes (HR, 0.74; 95% CI, 0.61–0.89). Conclusions Anthropometric measurements are more predictive of cataract than bioelectrical impedance measures. Diabetes plays an important role in the association between obesity and incident cataract.

Background Malleolar fracture, which is present in 37–53% of human ankle osteoarthritis (OA), is the most common type of fracture in the ankle joint. In spite of this, no rat animal model has been developed for this type of injury to date. Here, we established a rat ankle post-traumatic OA (PTOA) model induced by malleolar fracture; this model will be useful in ankle OA research. Methods Two-month-old male Sprague Dawley (SD) rats were randomized into 2 groups (n = 19 per group): 1) malleolus articular fracture, dislocation, and immediate reduction on the right joints and 2) malleolus articular fracture on the right ankle. The contralateral ankle joints were used as controls. The fracture and healing processes were confirmed and monitored by radiography. Changes in inflammation were monitored in vivo by fluorescence molecular tomography (FMT). Cartilage damage and changes in expression of OA-related genes were analyzed by histology, immunohistochemistry, Real-time quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) at 8 weeks post-surgery. Results X-rays showed that all fractures were healed at 8 weeks post-surgery. A reproducible, mild to moderate degree of OA cartilage damage with reduced aggrecan was detected by histology in all animals in both groups but there was no significant difference between the two groups. Decreased Col-II and increased Col-X and MMP-13 levels were detected by qPCR, immunohistochemistry, ELISA and FMT from both groups cartilage. Conclusions Malleolus articular fracture alone induces ankle OA with lesions on the central weight bearing area of the tibiotalar joint in rats. This model will provide a reproducible and useful tool for researchers to study ankle OA.

ObjectiveTo examine the association of physical activities (PA) with diabetic retinopathy (DR) progression based on a 10-year follow-up of a large cohort of working-aged diabetic populations in Australia.MethodsNine thousand and eighteen working-aged diabetic patients were enrolled from the baseline of the 45 and Up Study from New South Wales, Australia. Self-reported PA collected by questionnaire at baseline in 2006 was graded into low (ResultsIn the fully adjusted model, higher PA level was significantly associated with a lower risk of RPC incident (Cox-regression, p-value for trend = 0.002; medium vs. low, hazard ratio (HR) = 0.78, 95% Confidence Interval (CI): 0.61–0.98; high vs. low, HR = 0.61, 95%CI: 0.36–0.84. In addition, gender, body mass index, insulin treatment, family history of diabetes, history of cardiovascular disease were significant effect modifiers for the association between PA and RPC.ConclusionsHigher PA level was independently associated with a lower risk of DR progression among working-aged diabetic populations in this large cohort study.

Objectives SMAD3 is pivotal in the biology functions of various tumors. This study is aiming to study the relationship among SMAD3, long noncoding RNAs (lncRNAs) OPA-interacting protein 5 antisense transcript 1 (OIP5-AS1), and miR-143-3p, and their effects on cervical cancer. Methods In our research, real-time polymerase chain reaction and western blot assay were conducted to detect the expression level of messenger RNA and protein in tumor tissues and cells. Transfection of lncRNA OIP5-AS1, miR-143-3p, or SMAD3 was performed to investigate their potential effects on the function of cell as well as the relationship among them in cervical cell lines via 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) together with transwell assays or dual-luciferase reporter assay respectively. Results SMAD3, lncRNA OIP5-AS1 expression is significantly enhanced in cervical cancer tissues and cell lines, but miR-143-3p was inhibited. LncRNA OIP5-AS1 is demonstrated to mediate the physiological process of cervical cancer cells. Moreover, silencing SMAD3 via siRNA suppressed cell number, viability, migration and invasion, whereas overexpression of OIP5-AS1 promoted these abilities. Furthermore, lncRNA OIP5-AS1 exert its function via sponging miR-143-3p to regulate SMAD3 expression. Conclusions LncRNA OIP5-AS1 promoted SMAD3 expression via mediating miR-143-3p to promote migration and invasion of cervical cancer cells.

Objective: This study aimed to examine the association between baseline and changes in dietary quality assessed by the Alternative Healthy Eating Index-2010 (AHEI-2010) and abdominal aortic calcification (AAC) among community-dwelling older adults. Design: Population-based longitudinal study. Setting: A subset of the Melbourne Collaborative Cohort Study (MCCS). Participants: 262 community-dwelling adults (60% female) aged 53 ± 5 years at baseline. Measurements: Dietary intake was assessed using validated Food Frequency Questionnaires at baseline (1990-1994) and follow-up (2010-2011). AAC was evaluated by radiography and dual-energy x-ray absorptiometry (DXA) at follow-up. Results: Higher baseline AHEI-2010 score was associated with lower AAC severity by radiography [OR (95% CI) for Tertile 3 VS Tertile 1: 0.53 (0.29-0.99)] after adjustment for gender, age, physical activity, smoking, BMI, systolic blood pressure, plasma total cholesterol, calcium and energy intake. The association between AHEI-2010 and AAC severity by DXA was also significant in the multivariate-adjusted model [OR (95% CI) for Tertile 3 VS Tertile 1: 0.38 (0.20-0.70)]. Changes in AHEI-2010 over 18 years were not associated with AAC severity. Conclusion: Baseline but not the changes in AHEI-2010 was inversely associated with the risk of AAC severity suggesting that ahigh quality diet might help prevent or delay the progression of AAC in community-dwelling older adults and the benefits might be manifested over the long-term.

To evaluate the effect of 3D printing in treating trimalleolar fractures and its roles in physician-patient communication, thirty patients with trimalleolar fractures were randomly divided into the 3D printing assisted-design operation group (Group A) and the no-3D printing assisted-design group (Group B). In Group A, 3D printing was used by the surgeons to produce a prototype of the actual fracture to guide the surgical treatment. All patients underwent open reduction and internal fixation. A questionnaire was designed for doctors and patients to verify the verisimilitude and effectiveness of the 3D-printed prototype. Meanwhile, the operation time and the intraoperative blood loss were compared between the two groups. The fracture prototypes were accurately printed, and the average overall score of the verisimilitude and effectiveness of the 3D-printed prototypes was relatively high. Both the operation time and the intraoperative blood loss in Group A were less than those in Group B (P<0.05). Patient satisfaction using the 3D-printed prototype and the communication score were9.3±0.6points. A 3D-printed prototype can faithfully reflect the anatomy of the fracture site; it can effectively help the doctors plan the operation and represent an effective tool for physician-patient communication.

To determine whether adiposity assessed by dual-energy X-ray absorptiometry (DXA) compared to simple anthropometric assessments, are more predictive of abdominal aortic calcification (AAC), a risk factor for atherosclerosis. A cross-sectional study of 312 participants (60.3 % female) aged 70.6 ± 5.6 years was conducted in 2010-2011. AAC was assessed by radiography. Adiposity was estimated for whole body, trunk, android, gynoid and visceral regions using DXA in addition to body mass index (BMI), waist circumference (WC) and waist to hip ratio (WHR). WHR [tertile 1 as reference, OR (95 % CI) for tertile 3: 3.62 (1.35-9.72)] and android to gynoid fat ratio [tertile 3: 2.87 (1.03-8.01)] were independent predictors of AAC severity among men. Positive associations with AAC severity were observed for WC [tertile 1 as reference, OR for tertile 3: 2.46 (1.12-5.41)], % trunk fat mass [tertile 2: 3.26 (1.52-7.03)], % android fat mass [tertile 2: 2.42 (1.13-5.18), tertile 3: 2.20 (1.02-4.73)] and visceral fat area [tertile 2: 2.28 (1.06-4.87), tertile 3: 2.32 (1.01-5.34)] among women. Indices of total body composition, BMI and % body fat mass were not associated with AAC severity in either men or women. Simple anthropometric measures, WHR and WC were the best predictors of AAC severity in men and women respectively, although higher android to gynoid fat ratio and central fat, assessed by DXA, were also predictive of higher risks of AAC severity in men and women respectively. Our findings add to existing evidence that relatively inexpensive and easily obtained anthropometric measures can be clinically useful indicators of atherosclerosis risk.

To determine whether there is a correlation between the concentration of Indian hedgehog (Ihh) in synovial fluid (SF) and the severity of cartilage damage in the human knee joints, the knee cartilages from patients were classified using the Outer-bridge scoring system and graded using the Modified Mankin score. Expression of Ihh in cartilage and SF samples were analyzed with immunohistochemistry (IHC), western blot, and enzyme-linked immunosorbent assay (ELISA). Furthermore, we detected and compared Ihh protein levels in rat and mice cartilages between normal control and surgery-induced osteoarthritis (OA) group by IHC and fluorescence molecular tomography in vivo respectively. Ihh expression was increased 5.2-fold in OA cartilage, 3.1-fold in relative normal OA cartilage, and 1.71-fold in OA SF compared to normal control samples. The concentrations of Ihh in cartilage and SF samples was significantly increased in early-stage OA samples when compared to normal samples (r = 0.556; p < 0.001); however, there were no significant differences between normal samples and late-stage OA samples. Up-regulation of Ihh protein was also an early event in the surgery-induced OA models. Increased Ihh is associated with the severity of OA cartilage damage. Elevated Ihh content in human knee joint synovial fluid correlates with early cartilage lesions.

Background Childhood obesity and its related metabolic and psychological abnormalities are becoming serious health problems in China. Effective, feasible and practical interventions should be developed in order to prevent the childhood obesity and its related early onset of clinical cardiovascular diseases. The objective of this paper is to describe the design of a multi-centred random controlled school-based clinical intervention for childhood obesity in China. The secondary objective is to compare the cost-effectiveness of the comprehensive intervention strategy with two other interventions, one only focuses on nutrition education, the other only focuses on physical activity. Methods/Design The study is designed as a multi-centred randomised controlled trial, which included 6 centres located in Beijing, Shanghai, Chongqing, Shandong province, Heilongjiang province and Guangdong province. Both nutrition education (special developed carton style nutrition education handbook) and physical activity intervention (Happy 10 program) will be applied in all intervention schools of 5 cities except Beijing. In Beijing, nutrition education intervention will be applied in 3 schools and physical activity intervention among another 3 schools. A total of 9750 primary students (grade 1 to grade 5, aged 7-13 years) will participate in baseline and intervention measurements, including weight, height, waist circumference, body composition (bioelectrical impendence device), physical fitness, 3 days dietary record, physical activity questionnaire, blood pressure, plasma glucose and plasma lipid profiles. Data concerning investments will be collected in our study, including costs in staff training, intervention materials, teachers and school input and supervising related expenditure. Discussion Present study is the first and biggest multi-center comprehensive childhood obesity intervention study in China. Should the study produce comprehensive results, the intervention strategies would justify a national school-based program to prevent childhood obesity in China. Trial Registration Chinese clinical trial registry (Primary registry in the WHO registry network) Identifier: ChiCTR-TRC-00000402

ObjectiveTo determine whether educational level and overweight/obesity was associated with the development of diabetes among Chinese adult men and women.MethodsA cohort (2000-2011) of 10 704 participants aged 18-59 years (8 238 men, 2 466 women) in Qingdao Port Health Study (QPHS) were recruited in this study. The personal lifestyle, height, weight, waist circumference, resting heart rate, blood pressure, fasting blood glucose, total cholesterol, triglycerides and plasma uric acid were collected annually in a comprehensive health checkup program. Cox proportional hazards regression models were used to estimate the association of factors and incidence of diabetes.ResultsDuring 110 825 person-years of follow-up, 1 056 new onset cases (9.5 per 1 000 person-years) of diabetes were identified. With normal weight as reference, the multiple-adjusted hazard ratio (HR) (95%CI) of diabetes was 1.69(1.38-2.09) for overweight and 2.24(1.66-3.02) for obesity among men, which was 1.81(1.12-2.92) and 2.58(1.37-4.86) among women, respectively. Compared with the participants with high educational level, those with low educational level had a higher risk of diabetes (multiple-adjusted HR (95%CI): 1.43(1.11-1.86)) among men. The association was not found among women and the adjusted HR (95%CI) of diabetes was 1.56(0.89-2.76). The increased risks of low educational level were independent of mediators among men, through normal weight (P for trend = 0.0313) and overweight (P for trend = 0.0212) group but not obesity group (P for trend = 0.0957).ConclusionBaseline overweight/obesity was an independent risk factor for diabetes for both men and women. Low educational level was adversely associated with incidence of diabetes through normal weight, overweight and obesity groups, with the association being substantially attenuated by mediating factors only in the obesity group among men. The association was not found among women.

BackgroundThe association of dietary pattern with chronic diseases has been investigated widely in western countries. However, information is quite limited among children in China. Our study is aimed to identify the dietary patterns of Chinese children and examine their association with obesity and related cardiometabolic risk factors.MethodsA total of 5267 children were selected using multistage random sampling from 30 primary schools of 5 provincial capital cities in China. Dietary intake was derived from 24 hour dietary recall for three consecutive days. Anthropometric measurements, glucose and lipid profiles were obtained. Factor analysis combined with cluster analysis was used for identifying major dietary patterns. The associations of dietary patterns with obesity and related cardiometabolic risk factors were examined by logistic regression analysis.ResultsThree mutually exclusive dietary patterns were identified, which were labeled as the healthy dietary pattern, the transitive dietary pattern, and the Western dietary pattern. Compared with children of the healthy dietary pattern, the multiple-adjusted odds ratios (95% confidence interval (CI)) of obesity were 1.11 (0.89-1.38) for children with the transitive dietary pattern and 1.80 (1.15-2.81) for children with the Western dietary pattern, which was 1.31 (95%CI 1.09-1.56) and 1.71 (95%CI: 1.13-2.56), respectively, for abdominal obesity. The Western dietary pattern was associated with significantly higher concentrations of low-density lipoprotein cholesterol (PConclusionsThe Western dietary pattern characterized by red meat, eggs, refined grain and products, was positively associated with odds of obesity, the levels of plasma glucose, low-density lipoprotein cholesterol and triglycerides, and was inversely associated with the level of high-density lipoprotein cholesterol.