A new artificial intelligence system for both stomach and small-bowel capsule endoscopy.

BACKGROUND AND AIMS: Despite the benefits of artificial intelligence in small-bowel (SB) capsule endoscopy (CE) image reading, information on its application in the stomach and SB CE is lacking. METHODS: In this multicenter, retrospective diagnostic study, gastric imaging data were added to the deep learning-based SmartScan (SS), which has been described previously. A total of 1069 magnetically controlled GI CE examinations (comprising 2,672,542 gastric images) were used in the training phase for recognizing gastric pathologies, producing a new artificial intelligence algorithm named SS Plus. A total of 342 fully automated, magnetically controlled CE examinations were included in the validation phase. The performance of both senior and junior endoscopists with both the SS Plus-assisted reading (SSP-AR) and conventional reading (CR) modes was assessed. RESULTS: SS Plus was designed to recognize 5 types of gastric lesions and 17 types of SB lesions. SS Plus reduced the number of CE images required for review to 873.90 (median, 1000; interquartile range [IQR], 814.50-1000) versus 44,322.73 (median, 42,393; IQR, 31,722.75-54,971.25) for CR. Furthermore, with SSP-AR, endoscopists took 9.54 minutes (median, 8.51; IQR, 6.05-13.13) to complete the CE video reading. In the 342 CE videos, SS Plus identified 411 gastric and 422 SB lesions, whereas 400 gastric and 368 intestinal lesions were detected with CR. Moreover, junior endoscopists remarkably improved their CE image reading ability with SSP-AR. CONCLUSIONS: Our study shows that the newly upgraded deep learning-based algorithm SS Plus can detect GI lesions and help improve the diagnostic performance of junior endoscopists in interpreting CE videos.

Associations of soy product intake with all-cause, cardiovascular disease and cancer mortality: Guangzhou Biobank Cohort Study and updated meta-analyses.

PURPOSE: We examined the associations of soy product intake with all-cause, cardiovascular disease (CVD), and cancer mortality and mediations through CVD risk factors based on the Guangzhou Biobank Cohort Study (GBCS), and conducted updated meta-analyses. METHODS: A total of 29,825 participants aged 50 + years were included. Causes of death were identified through record linkage. Soy product intake was assessed by food frequency questionnaire. Cox proportional hazards regression was used to analyze the associations between soy product intake and mortality, yielding hazard ratios (HRs) and 95% confidence intervals (CIs). Mediation analyses with CVD risk factors as mediators, and updated meta-analyses were conducted. RESULTS: During 454,689 person-years of follow-up, 6899 deaths occurred, including 2694 CVD and 2236 cancer. Participants who consumed soy product of 1-6 portions/week, versus no consumption, had significantly lower risks of all-cause and CVD mortality (adjusted HR (95% CI) 0.91 (0.86, 0.97) and 0.87 (0.79, 0.96), respectively). In participants who consumed soy product of ≥ 7 portions/week, the association of higher intake with lower CVD mortality was modestly mediated by total cholesterol (4.2%, 95% CI 1.0-16.6%). Updated meta-analyses showed that the highest level of soy product intake, versus the lowest, was associated with lower risks of all-cause and CVD mortality (pooled HR (95% CI) 0.92 (0.88, 0.96) and 0.92 (0.87, 0.98), respectively). CONCLUSION: Moderate and high soy product intake were associated with lower risks of all-cause and CVD mortality. Our findings provide support for current dietary guidelines recommending moderate soy product intake, and contribute additional evidence regarding the potential protective effects of high soy product intake.

Association of novel and conventional obesity indices with colorectal cancer risk in older Chinese: a 14-year follow-up of the Guangzhou Biobank Cohort Study.

BACKGROUND: Visceral adiposity index (VAI) and a body shape index (ABSI) were newly developed indices for visceral fat mass. Whether they are superior to conventional obesity indices in predicting colorectal cancer (CRC) remains unclear. We examined the associations of VAI and ABSI with CRC risk, and investigated their performance in discriminating CRC risk compared with conventional obesity indices in the Guangzhou Biobank Cohort Study. METHODS: A total of 28,359 participants aged 50 + years without cancer history at baseline (2003-8) were included. CRC were identified from the Guangzhou Cancer Registry. Cox proportional hazards regression was used to assess the association of obesity indices with the CRC risk. Discriminative abilities of obesity indices were assessed using Harrell's C-statistic. RESULTS: During an average follow-up of 13.9 (standard deviation = 3.6) years, 630 incident CRC cases were recorded. After adjusting for potential confounders, the hazard ratio (95% confidence interval) of incident CRC for per standard deviation increment in VAI, ABSI, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) was 1.04 (0.96, 1.12), 1.13 (1.04, 1.22), 1.08 (1.00, 1.17), 1.15 (1.06, 1.24), 1.16 (1.08, 1.25)and 1.13 (1.04, 1.22), respectively. Similar results for colon cancer were found. However, the associations of obesity indices with risk of rectal cancer were non-significant. All obesity indices showed similar discriminative abilities (C-statistics from 0.640 to 0.645), with WHR showing the highest whilst VAI and BMI the lowest. CONCLUSIONS: ABSI, but not VAI, was positively associated with a higher risk of CRC. However, ABSI was not superior to the conventional abdominal obesity indices in predicting CRC.

Quantity and Variety in Fruit and Vegetable Consumption and Mortality in Older Chinese: A 15-year Follow-Up of a Prospective Cohort Study.

BACKGROUND: Independent associations of quantity and variety of fruit and vegetables (FVs) with mortality in older people are still unclear. OBJECTIVES: This study aimed to explore the association between the quantity and variety in FV consumption and mortality in older Chinese. METHODS: A total of 19,597 participants of the Guangzhou Biobank Cohort Study aged >50 y were recruited from 2003 to 2006 and followed up until April 2021. The diet was assessed using a 300-item validated FFQ. Variety as a continuous variable was defined as the number of unique FV items (excluding potatoes, legumes, and fruit juices) intake per week over the past week. The associations of quantity and variety of FVs with mortality were analyzed, and analyses by the color of edible parts was performed. Multivariable Cox regression yielded HRs and 95% CIs. RESULTS: During 286,821 person-year of follow-up, 4385 deaths occurred, including 1678 cardiovascular diseases (CVD), 1450 cancer, and 1257 other causes. Compared with the lowest quintile of variety in FV, the highest quintile was associated with lower risks of all-cause (HR: 0.81; 95% CI: 0.73-0.89) and CVD mortality (HR: 0.79; 95% CI 0.67-0.92). A greater variety of green and white FV intake was associated with lower risks of all-cause and CVD morality, and a greater variety of red/purple FV intake was associated with lower risks of all-cause and cancer mortality. However, the quantity of FV intake showed no association with all-cause, CVD, and cancer mortality. CONCLUSION: Our findings have first showed that the variety, rather than quantity, in FV intake was associated with a lower risk of mortality in older Chinese. Dietary guidelines may recommend increasing the variety in FV intake, especially green, red/purple, and white FVs in older people.

Cereal intake and mortality in older Chinese: a 15-year follow-up of a prospective cohort study.

PURPOSE: We examined the association between whole grain and refined grain intake with all-cause, cancer and cardiovascular disease (CVD) mortality using the data from the Guangzhou Biobank Cohort Study. METHODS: 19,597 participants aged 50+ years were recruited from 2003 to 2006 and followed-up until April 2021. Multivariable Cox regression was used to calculate hazard radios (HRs) and 95% confidence intervals (CIs). Substitution analysis was used to replace a serving (50 g/day) of whole grain with a serving of refined grain. RESULTS: During 286,821 person-years of follow-up, 4385 deaths occurred, including 1450 from cancer, 1678 from CVD and 1257 from other causes. Compared with never whole grain intake, the highest intake category of whole grain (> 300 g/week) was associated with lower risk of all-cause (HR 0.90, 95% CI 0.82-0.98) and CVD mortality (HR 0.85, 0.74-0.98). Compared with the low-intake category of refined grain (< 500 g/day), the highest intake category (> 900 g/week) was associated with a lower risk of cancer mortality (HR 0.76, 0.62-0.95), but a higher risk of CVD mortality (HR 1.25, 1.03-1.51). No significant associations were found between whole grain intake and cancer mortality nor refined grain and all-cause mortality. The HRs of all-cause, cancer and CVD mortality substituting a serving of whole grain for refined grain were 0.96 (0.94-0.99), 1.01 (0.99-1.02) and 0.95 (0.90-0.99), respectively. CONCLUSION: We have first shown that in older Chinese, whole grain intake was associated with lower risk of all-cause and CVD mortality. Our results suggest that intake of whole grain of at least 300 g/week and refined grain of ≤ 900 g/day might be suitable for older Asian. Substituting 50 g/day of whole grain for refined grain was associated with a 4-5% lower risk of all-cause and CVD mortality.

A liposomal carbohydrate vaccine, adjuvanted with an NKT cell agonist, induces rapid and enhanced immune responses and antibody class switching.

BACKGROUND: Congenital disorders of glycosylation (CDGs) are genetic diseases caused by gene defects in glycan biosynthesis pathways, and there is an increasing number of patients diagnosed with CDGs. Because CDGs show many different clinical symptoms, their accurate clinical diagnosis is challenging. Recently, we have shown that liposome nanoparticles bearing the ALG1-CDG and PMM2-CDG biomarkers (a tetrasaccharide: Neu5Ac-α2,6-Gal-ß1,4-GlcNAc-ß1,4-GlcNAc) stimulate a moderate immune response, while the generated antibodies show relatively weak affinity maturation. Thus, mature antibodies with class switching to IgG are desired to develop high-affinity antibodies that may be applied in medical applications. RESULTS: In the present study, a liposome-based vaccine platform carrying a chemoenzymatic synthesized phytanyl-linked tetrasaccharide biomarker was optimized. The liposome nanoparticles were constructed by dioleoylphosphatidylcholine (DOPC) to improve the stability and immunogenicity of the vaccine, and adjuvanted with the NKT cell agonist PBS57 to generate high level of IgG antibodies. The results indicated that the reformulated liposomal vaccine stimulated a stronger immune response, and PBS57 successfully induce an antibody class switch to IgG. Further analyses of IgG antibodies elicited by liposome vaccines suggested their specific binding to tetrasaccharide biomarkers, which were mainly IgG2b isotypes. CONCLUSIONS: Immunization with a liposome vaccine carrying a carbohydrate antigen and PBS57 stimulates high titers of CDG biomarker-specific IgG antibodies, thereby showing great potential as a platform to develop rapid diagnostic methods for ALG1-CDG and PMM2-CDG.

Association of Multi-Dimensional Factors with Accelerating Age and Constructing a Healthy Lifestyle Index: Guangzhou Biobank Cohort Study.

INTRODUCTION: Ageing process is influenced by multi-dimensional factors collectively. Previous studies examined association of one separate factor with mortality without considering different manifestations of ageing process. We investigated associations of multi-dimensional factors with accelerating age (AA), a proxy to quantify ageing, in older Chinese. METHODS: 9,831 participants from Guangzhou Biobank Cohort Study were included. Four exposure domains of 15 variables including demographic and socio-economic factors, lifestyle factors, stress across the life course, and common diseases were assessed. AA was calculated based on chronological age and eight biomarkers. Traditional multivariable linear and Bayesian Network (BN) models were used. RESULTS: In both traditional and BN models, male sex, smoking, alcohol use, physical inactivity, greater waist circumference, and body mass index (BMI) were associated with higher AA, with the adjusted ß (95% confidence intervals) being 2.75 (2.40-3.09), 1.31 (0.87-1.76), 1.35 (0.55-2.15), 0.64 (0.40-0.88), 0.09 (0.06-0.11), and 0.13 (0.07-0.19) years, respectively. A Healthy Lifestyle Index (HLI) was constructed including the above lifestyle factors (non-smoking, non-alcohol use, physically active, non-central, and non-general obesity) with a point assigned for each. A higher index indicates healthier lifestyle. Compared with participants with an HLI of 5, those with an HLI of 0-2 had 2.90 (2.48-3.32) years older AA. CONCLUSIONS: Male sex, smoking, alcohol use, physical inactivity, greater waist circumference, and BMI were associated with higher AA by 0.09-2.75 years, suggesting that adopting a healthy lifestyle may alleviate process of phenotypic ageing.

Association of fish and meat consumption with non-alcoholic fatty liver disease: Guangzhou Biobank Cohort Study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Unhealthy dietary habit is one of major risk factors of NAFLD. However, the associations between specific types of fish and meat consumption and NAFLD remain inconclusive. We explored the associations of fish and meat consumption with NAFLD risk in middle-aged and older Chinese. METHODS: We collected information on 1,862 participants aged 50 years or older from Guangzhou Biobank Cohort Study in 2009 to 2010. Fish and meat consumption was assessed using a validated food-frequency questionnaire. NAFLD was diagnosed by ultrasound. Multivariable logistic regression was used to examine the associations of fish and meat consumption with the presence of NAFLD. RESULTS: The average age was 61.0 (standard deviation = 6.5) years for the participants, 50.2% were women, and 37.2% were diagnosed with NAFLD. After adjusting for age, sex, education, family income, occupation, smoking status, drinking status, physical activity and several metabolic traits, compared with 0 serving/week (one serving = 50 g), fatty fish consumption of ≥ 3 servings/week showed higher odds of NAFLD (odds ratio (OR) and 95% confidence interval (CI): 1.64 (1.12, 2.39)). The highest (≥ 11 servings/week of red meat and poultry; ≥ 3 servings/week of processed meat) versus the lowest (0-3 servings/week of red meat and poultry; 0 serving/week of processed meat) consumption of all other types of meats, including red meat, poultry and processed meat, showed no association with NAFLD (1.17 (0.75, 1.81), 1.02 (0.42, 2.50) and 0.85 (0.50, 1.45), respectively). Aquatic and sea food, and red meat had negative indirect effects on NAFLD via systolic blood pressure and/or high-density lipoprotein cholesterol. Processed meat had positive indirect effects on NAFLD via body mass index, waist circumference, fasting plasma glucose and triglycerides. CONCLUSION: High consumption of fatty fish was associated with higher NAFLD risk. Our results, if causal, provide evidence that limiting consumption of fatty fish can be considered as part of NAFLD lifestyle prevention and treatment.

In vitro and in vivo evaluation of DC-targeting PLGA nanoparticles encapsulating heparanase CD4+ and CD8+ T-cell epitopes for cancer immunotherapy.

Heparanase has been identified as a universal tumor-associated antigen, but heparanase epitope peptides are difficult to recognize. Therefore, it is necessary to explore novel strategies to ensure efficient delivery to antigen-presenting cells. Here, we established a novel immunotherapy model targeting antigens to dendritic cell (DC) receptors using a combination of heparanase CD4+ and CD8+ T-cell epitope peptides to achieve an efficient cytotoxic T-cell response, which was associated with strong activation of DCs. First, pegylated poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs) were used to encapsulate a combined heparanase CD4+ and CD8+ T-cell epitope alone or in combination with Toll-like receptor 3 and 7 ligands as a model antigen to enhance immunogenicity. The ligands were then targeted to DC cell-surface molecules using a DEC-205 antibody. The binding and internalization of these PLGA NPs and the activation of DCs, the T-cell response and the tumor-killing effect were assessed. The results showed that PLGA NPs encapsulating epitope peptides (mHpa399 + mHpa519) could be targeted to and internalized by DCs more efficiently, stimulating higher levels of IL-12 production, T-cell proliferation and IFN-γ production by T cells in vitro. Moreover, vaccination with DEC-205-targeted PLGA NPs encapsulating combined epitope peptides exhibited higher tumor-killing efficacy both in vitro and in vivo. In conclusion, delivery of PLGA NP vaccines targeting DEC-205 based on heparanase CD4+ and CD8+ T-cell epitopes are suitable immunogens for antitumor immunotherapy and have promising potential for clinical applications.

Associations of face-to-face and non-face-to-face social isolation with all-cause and cause-specific mortality: 13-year follow-up of the Guangzhou Biobank Cohort study.

BACKGROUND: Although social isolation has been associated with a higher mortality risk, little is known about the potential different impacts of face-to-face and non-face-to-face isolation on mortality. We examined the prospective associations of four types of social isolation, including face-to-face isolation with co-inhabitants and non-co-inhabitants, non-face-to-face isolation, and club/organization isolation, with all-cause and cause-specific mortality separately. METHODS: This prospective cohort study included 30,430 adults in Guangzhou Biobank Cohort Study (GBCS), who were recruited during 2003-2008 and followed up till Dec 2019. RESULTS: During an average of 13.2 years of follow-up, 4933 deaths occurred during 396,466 person-years. Participants who lived alone had higher risks of all-cause (adjusted hazard ratio (AHR) 1.24; 95% confidence interval (CI) 1.04-1.49) and cardiovascular disease (CVD) (1.61; 1.20-2.03) mortality than those who had ≥ 3 co-habitant contact after adjustment for thirteen potential confounders. Compared with those who had ≥ 1 time/month non-co-inhabitant contact, those without such contact had higher risks of all-cause (1.60; 1.20-2.00) and CVD (1.91; 1.20-2.62) mortality. The corresponding AHR (95% CI) in participants without telephone/mail contact were 1.27 (1.14-1.42) for all-cause, 1.30 (1.08-1.56) for CVD, and 1.37 (1.12-1.67) for other-cause mortality. However, no association of club/organization contact with the above mortality and no association of all four types of isolation with cancer mortality were found. CONCLUSIONS: In this cohort study, face-to-face and non-face-to-face isolation were both positively associated with all-cause, CVD-, and other-cause (but not cancer) mortality. Our finding suggests a need to promote non-face-to-face contact among middle-aged and older adults.

Life course exposures continually shape antibody profiles and risk of seroconversion to influenza.

Complex exposure histories and immune mediated interactions between influenza strains contribute to the life course of human immunity to influenza. Antibody profiles can be generated by characterizing immune responses to multiple antigenically variant strains, but how these profiles vary across individuals and determine future responses is unclear. We used hemagglutination inhibition titers from 21 H3N2 strains to construct 777 paired antibody profiles from people aged 2 to 86, and developed novel metrics to capture features of these profiles. Total antibody titer per potential influenza exposure increases in early life, then decreases in middle age. Increased titers to one or more strains were seen in 97.8% of participants during a roughly four-year interval, suggesting widespread influenza exposure. While titer changes were seen to all strains, recently circulating strains exhibited the greatest titer rise. Higher pre-existing, homologous titers at baseline reduced the risk of seroconversion to recent strains. After adjusting for homologous titer, we also found an increased frequency of seroconversion against recent strains among those with higher immunity to older previously exposed strains. Including immunity to previously exposures also improved the deviance explained by the models. Our results suggest that a comprehensive quantitative description of immunity encompassing past exposures could lead to improved correlates of risk of influenza infection.

Association of alcohol drinking with incident type 2 diabetes and pre-diabetes: The Guangzhou Biobank Cohort Study.

AIMS: We examined associations of baseline alcohol drinking with incident type 2 diabetes (T2D) or impaired fasting glucose (IFG), and explore whether the associations were modified by genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-1B (ADH1B). MATERIALS AND METHODS: All participants were aged 50+ (mean = 60.45; standard deviation = 6.88) years. Information of alcohol consumption was collected at baseline from 2003 to 2008. Incident T2D was defined as fasting glucose ≥7.0 mmol/L or post-load glucose ≥11.1 mmol/L at follow-up examination (2008-2012), self-reported T2D and/or initiation of hypoglycaemia medication or insulin during follow-up. Impaired fasting glucose was defined as fasting glucose ≥5.6 mmol/L and <7 mmol/L. RESULTS: Of 15,716 participants without diabetes and 11,232 participants without diabetes and IFG at baseline, 1624 (10.33%) developed incident T2D and 1004 (8.94%) developed incident IFG during an average 4 years of follow-up. After multivariable adjustments, compared with never drinking, occasional or moderate alcohol drinking was not associated with risk of incident hyperglycaemia (T2D + IFG) (odds ratio (OR) = 1.10, 95% confidence interval (CI) 0.95-1.27, and 0.90 (0.69-1.18), respectively), whereas heavy alcohol drinking was associated with a higher risk of incident hyperglycaemia (T2D + IFG) (OR = 1.82, 95% CI 1.24-2.68). No interactions of sex, overweight/obesity and genetic polymorphisms of ADH1B/ALDH2 genes with alcohol drinking on incident T2D and/or IFG were found (P for interaction from 0.12 to 0.85). CONCLUSIONS: Our results support a detrimental effect of heavy alcohol use on IFG and T2D. No protective effect was found for those carrying lower risk alleles for ADH1B/ALDH2 genes.

Diet Quality Scores Are Positively Associated with Whole Blood-Derived Mitochondrial DNA Copy Number in the Framingham Heart Study.

BACKGROUND: The association between diet quality and mitochondrial DNA copy number (mtDNA-CN) remains to be examined. OBJECTIVES: We aimed to study the relation between diet quality and mtDNA-CN. METHODS: We analyzed data from 2931 Framingham Heart Study (FHS) participants (mean age of 57 y, 55% females). Whole-genome sequencing was used to calculate mtDNA-CN from whole-blood samples. We examined the cross-sectional associations between 3 diet quality scores, the Dietary Approaches to Stop Hypertension (DASH) score, the Alternative Healthy Eating Index (AHEI), and the Mediterranean diet score (MDS), and mtDNA-CN. Linear mixed models were used to account for maternal lineage. RESULTS: We observed that a higher DASH score was positively associated with mtDNA-CN after adjusting for sex, age, energy intake, smoking status, alcohol intake, and physical activity level. A 1-SD increase in the DASH score was associated with a 0.042-SD greater mtDNA-CN (95% CI: 0.007, 0.077; P = 0.02). Similarly, for each SD increase in AHEI and MDS, the mtDNA-CN SD increased by 0.056 (95% CI: 0.019, 0.092; P = 0.003) and 0.047 (95% CI: 0.01, 0.083; P = 0.01), respectively. Diet quality scores were associated with neutrophil and lymphocyte counts but not platelet counts, e.g., for a 1-SD increase in the DASH, neutrophils decreased by 0.8% (95% CI: 0.5%, 1.1%; P = 4.1 × 10-6), lymphocytes increased by 0.7% (95% CI: 0.4%, 1%, P = 1.2 × 10-5), and there was no significant change in platelet number (0.1 × 1000/µL; 95% CI: -1.6, 1.9; P = 0.89). Further adjustment for neutrophil, lymphocyte, and platelet counts and the associations between diet quality scores and mtDNA-CN were completely attenuated to nonsignificant (P = 0.95, 0.54, and 0.91, respectively). CONCLUSIONS: We observed that higher diet quality is associated with a greater whole-blood derived mtDNA-CN in middle-aged to older adult FHS participants, and that blood cell composition, particularly neutrophil counts, attenuated the association between diet quality and mtDNA-CN.

Association of alcohol use with memory decline in middle-aged and older Chinese: a longitudinal cohort study.

BACKGROUND: Previous studies on associations of alcohol use with memory decline showed inconclusive results. We examined these associations using longitudinal data from the Guangzhou Biobank Cohort Study (GBCS) and explored whether these associations varied by sex and age group. METHODS: Memory function was assessed by delayed 10-word recall test (DWRT) and immediate 10-word recall test (IWRT) at both baseline (2003-2008) and follow-up (2008-2012) examinations, expressed as the mean annual change and mean annual rate of change in scores. Memory cognitive impairment was defined by DWRT scores of less than 4. Multivariable linear regression models and restricted cubic spline were used for data analysis. RESULTS: Of 14,827 participants without memory cognitive impairment at baseline, 90.2% were never or occasional drinkers, 5% moderate drinkers, 1.5% excessive drinkers, and 3.3% former drinkers. The mean (standard deviation) age was 60.6 (6.6) years old. During an average of 4.1 years follow-up, 1000 (6.7%) participants developed memory cognitive impairment. After adjusting for confounders, compared with never or occasional drinkers, moderate and excessive drinkers had significant decline in DWRT scores (ß, 95% confidence interval (CI) = -0.04 (-0.08 to -0.01), and - 0.07 (-0.14 to 0.01), respectively), and IWRT scores (ß, 95% CI = -0.10 (-0.19 to -0.01), and - 0.15 (-0.30 to 0.01), respectively) annually. With respect to the mean annual rate of change, moderate and excessive drinkers also showed greater decline in DWRT scores (ß, 95% CI = -1.02% (-1.87% to -0.16%), and - 1.64% (-3.14% to -0.14%), respectively). The associations did not vary by sex and age group (all P values for interaction ≥ 0.10). CONCLUSION: Compared to never or occasional alcohol use, moderate and excessive alcohol users had greater memory decline and the associations did not vary by sex and age group.

Hearing loss and depressive symptoms in older Chinese: whether social isolation plays a role.

BACKGROUND: Existing evidence links hearing loss to depressive symptoms, with the extent of association and underlying mechanisms remaining inconclusive. We conducted a cross-sectional study to examine the association of hearing loss with depressive symptoms and explored whether social isolation mediated the association. METHODS: Eight thousand nine hundred sixty-two participants from Guangzhou Biobank Cohort Study were included. Data on self-reported hearing status, the 15-item Geriatric Depression Scale (GDS-15), social isolation and potential confounders were collected by face-to-face interview. RESULTS: The mean (standard deviation) age of participants was 60.2 (7.8) years. The prevalence of poor and fair hearing was 6.8% and 60.8%, respectively. After adjusting for age, sex, household income, education, occupation, smoking, alcohol use, self-rated health, comorbidities, compared with participants who had normal hearing, those with poor hearing (ß = 0.74, 95% confidence interval (CI) 0.54, 0.94) and fair hearing (ß = 0.59, 95% CI 0.48, 0.69) had higher scores of GDS-15. After similar adjustment, those with poor hearing (odds ratio (OR) = 2.13, 95% CI 1.65, 2.74) or fair hearing (OR = 1.68, 95% CI 1.43, 1.99) also showed higher odds of depressive symptoms. The association of poor and fair hearing with depressive symptoms attenuated slightly but not substantially after additionally adjusting for social isolation. In the mediation analysis, the adjusted proportion of the association mediated through social isolation was 9% (95% CI: 6%, 22%). CONCLUSION: Poor hearing was associated with a higher risk of depressive symptoms, which was only partly mediated by social isolation. Further investigation of the underlying mechanisms is warranted.

Obesity indicators as mediators of association between daytime napping and type 2 diabetes mellitus: the Guangzhou Biobank Cohort Study.

OBJECTIVE: To examine the mediating effect of obesity indicators on the association between daytime napping and type 2 diabetes mellitus (T2DM) qualitatively and quantitatively using baseline data from the Guangzhou Biobank Cohort Study. METHODS: Twenty-nine thousand three hundred fifty-five participants aged 50+ years were included in this cross-sectional study. Mediation analysis was used to assess the mediating effect of body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) on the association between daytime napping and T2DM after adjustment for sex, age, education, occupation, smoking status, alcohol use and physical activity. RESULTS: The mean (standard deviation) age of participants was 61.5 ( 7.1) years. The prevalence of T2DM and daytime napping was 12.5% and 65.2%, respectively. After adjustment for potential confounders, WC, WHR and WHtR showed partial mediating effects on the association between daytime napping and T2DM, with the proportion (95% confidence interval) of mediation effect being 10.17% (8.14-14.43%), 14.91% (11.95-21.24%) and 9.36% (7.49-13.29%), respectively. No mediating effect of BMI or HC on the association between daytime napping and T2DM was found. CONCLUSIONS: Our results showed significant mediating effects of WC, WHR and WHtR on the association between daytime napping and T2DM, suggesting that waist circumference management could be important in daytime nappers.

Mendelian Randomization Focused Analysis of Vitamin D on the Secondary Prevention of Ischemic Stroke.

BACKGROUND AND PURPOSE: Experimental studies showed vitamin D (Vit-D) could promote vascular regeneration and repair. Prior randomized studies had focused mainly on primary prevention. Whether Vit-D protects against ischemic stroke and myocardial infarction recurrence among subjects with prior ischemic insults was unknown. Here, we dissected through Mendelian randomization any effect of Vit-D on the secondary prevention of recurrent ischemic stroke and myocardial infarction. METHODS: Based on a genetic risk score for Vit-D constructed from a derivation cohort sample (n=5331, 45% Vit-D deficient, 89% genotyped) via high-throughput exome-chip screening of 12 prior genome-wide association study-identified genetic variants of Vit-D mechanistic pathways (rs2060793, rs4588, and rs7041; F statistic, 73; P<0.001), we performed a focused analysis on prospective recurrence of myocardial infarction (MI) and ischemic stroke in an independent subsample with established ischemic disease (n=441, all with prior first ischemic event; follow-up duration, 41.6±14.3 years) under a 2-sample, individual-data, prospective Mendelian randomization approach. RESULTS: In the ischemic disease subsample, 11.1% (n=49/441) had developed recurrent ischemic stroke or MI and 13.3% (n=58/441) had developed recurrent or de novo ischemic stroke/MI. Kaplan-Meier analyses showed that genetic risk score predicted improved event-free survival from recurrent ischemic stroke or MI (log-rank, 13.0; P=0.001). Cox regression revealed that genetic risk score independently predicted reduced risk of recurrent ischemic stroke or MI combined (hazards ratio, 0.62 [95% CI, 0.48-0.81]; P<0.001), after adjusted for potential confounders. Mendelian randomization supported that Vit-D is causally protective against the primary end points of recurrent ischemic stroke or MI (Wald estimate: odds ratio, 0.55 [95% CI, 0.35-0.81]) and any recurrent or de novo ischemic stroke/MI (odds ratio, 0.64 [95% CI, 0.42-0.91]) and recurrent MI alone (odds ratio, 0.52 [95% CI, 0.30-0.81]). CONCLUSIONS: Genetically predicted lowering in Vit-D level is causal for the recurrence of ischemic vascular events in persons with prior ischemic stroke or MI.

Brain-derived neurotrophic factor gene variants and obesity in former smokers.

OBJECTIVE: From genome-wide association studies, brain-derived neurotrophic factor (BDNF) locus on chromosome 11 was the only SNP associated with both smoking and body mass index (BMI) in European, African and Asian population. This study aims to explore the unique genetic predisposition to obesity in former smokers by examining the effects of BDNF on BMI and waist circumference (WC). METHODS: The study design is case-control study with a cohort validation in supplementary. We included 15,072 ethnic Chinese participants in the Guangzhou Biobank Cohort Study (GBCS) with data of four BDNF SNPs related to both BMI and smoking behavior. We used baseline smoke exposure data in 2003-2007 and follow-up outcomes of general obesity (by BMI) and central obesity (WC) in 2008-2012. Odds ratios (ORs) and 95% confidence intervals (CIs) for general obesity and central obesity associated with these SNPs were derived from logistic regression. RESULTS: Of 15,072 participants (3169 men and 11,903 women), 1664 (11.0%) had general and 7868 (52.2%) had central obesity. In 1233 former smokers, the rs6265 GG, versus AA, genotype was associated with higher risks of general obesity (OR = 1.79, 95% CI = 1.06-3.01) and central obesity (OR = 2.08, 95% CI = 1.47-2.92) after adjustment. These associations were not significant in never or current smokers. In former heavy (≥20 cigarettes/day) smokers, the rs6265 GG genotype showed a higher odds for general obesity (OR = 2.15, 95% CI = 1.05-4.40), while no association was found in former light (1-9 cigarettes/day) smokers. Similar results were found for the association of rs6265 with central obesity and for the associations of other two BDNF SNPs (rs4923457 and rs11030104) with both general and central obesity. CONCLUSIONS: We firstly identified the genetic predisposition (BDNF SNPs) to general and central obesity in former smokers, particularly in former heavy smokers. The different associations of the SNPs for general/central obesity in different smoke exposure groups may be related to the competitive performance of the sites and epigenetic modification, which needs further study.

Metabolite patterns link diet, obesity, and type 2 diabetes in a Hispanic population.

INTRODUCTION: Obesity is a precursor of type 2 diabetes (T2D). OBJECTIVES: Our aim was to identify metabolic signatures of T2D and dietary factors unique to obesity. METHODS: We examined a subsample of the Boston Puerto Rican Health Study (BPRHS) population with a high prevalence of obesity and T2D at baseline (n = 806) and participants (without T2D at baseline) at 5-year follow-up (n = 412). We determined differences in metabolite profiles between T2D and non-T2D participants of the whole sample and according to abdominal obesity status. Enrichment analysis was performed to identify metabolic pathways that were over-represented by metabolites that differed between T2D and non-T2D participants. T2D-associated metabolites unique to obesity were examined for correlation with dietary food groups to understand metabolic links between dietary intake and T2D risk. False Discovery Rate method was used to correct for multiple testing. RESULTS: Of 526 targeted metabolites, 179 differed between T2D and non-T2D in the whole sample, 64 in non-obese participants and 120 unique to participants with abdominal obesity. Twenty-four of 120 metabolites were replicated and were associated with T2D incidence at 5-year follow-up. Enrichment analysis pointed to three metabolic pathways that were overrepresented in obesity-associated T2D: phosphatidylethanolamine (PE), long-chain fatty acids, and glutamate metabolism. Elevated intakes of three food groups, energy-dense takeout food, dairy intake and sugar-sweetened beverages, associated with 13 metabolites represented by the three pathways. CONCLUSION: Metabolic signatures of lipid and glutamate metabolism link obesity to T2D, in parallel with increased intake of dairy and sugar-sweetened beverages, thereby providing insight into the relationship between dietary habits and T2D risk.

Risk Factors Associated with Vitamin D Status among Older Puerto Rican Adults.

BACKGROUND: Vitamin D deficiency has been associated with health problems globally, but there is limited information on vitamin D status and associated risk factors among adults in underserved populations. OBJECTIVE: This study aimed to identify risk factors for vitamin D deficiency/insufficiency among Puerto Rican adults from the Boston Puerto Rican Health Study (BPRHS). METHODS: A total of 822 adults (45-75 y, at baseline) were included in these analyses. Deficiency was defined as serum 25-hydroxyvitamin D [25(OH)D] <30 and insufficiency as 30 to <50 nmol/L. Dietary intake was assessed with a validated FFQ. Associations between risk factors, including dietary vitamin D, supplement use, ancestry, skin pigmentation, months in the past year spent in a southern climate, and serum 25(OH)D were assessed with multivariable general linear models. RESULTS: Approximately 13% of participants were deficient in 25(OH)D and another 43% insufficient. Skin pigment was associated with 25(OH)D using 3 measures, greater African ancestry (ß ± SE) (-7.74 ± 2.91, P = 0.01); interviewer assessed dark or medium, compared with white, skin tone, (-5.09 ± 2.19, P = 0.02 and -5.89 ± 1.58, P < 0.001, respectively); and melanin index of the upper inner right arm, assessed using a spectrophotometer (-2.04 ± 0.84, P = 0.02). After adjusting for ancestry, factors associated with lower serum 25(OH)D included smoking (-4.49 ± 1.58, P = 0.01); BMI (-0.21 ± 0.10, P = 0.04); and spring compared with autumn blood draw (-4.66 ± 1.68, P = 0.004). Factors associated with higher serum 25(OH)D included female sex compared with male (4.03 ± 1.58, P = 0.01); dietary vitamin D intake µg/d (0.71 ± 0.25, P < 0.004); vitamin D supplement use (4.50 ± 1.87, P = 0.02); income to poverty ratio (0.01 ± 0.01, P = 0.06), and months in a southern climate during the past year (0.96 ± 0.56, P = 0.09). CONCLUSIONS: Vitamin D deficiency/insufficiency was prevalent in this Puerto Rican population living in the northeastern USA. Several factors were associated with this, which may assist in identifying those at risk. Interventions are needed to improve serum 25(OH)D concentration, particularly among those with limited exposure to sunlight.