Inter- and Intraobserver Variability on Endoscopic Scoring Systems in Crohn's Disease and Ulcerative Colitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Endoscopy scoring is a key component in the diagnosis of ulcerative colitis (UC) and Crohn's disease (CD). Variability in endoscopic scoring can impact patient trial eligibility and treatment effect measurement. In this study, we examine inter- and intraobserver variability of inflammatory bowel disease endoscopic scoring systems in a systematic review and meta-analysis. METHODS: We included observational studies that evaluated the inter- and intraobserver variability using UC (endoscopic Mayo Score [eMS], Ulcerative Colitis Endoscopic Index of Severity [UCEIS]) or CD (Crohn's Disease Endoscopic Index of Severity [CDEIS], Simple Endoscopic Score for Crohn's Disease [SES-CD]) systems among adults (≥18 years of age) and were published in English. The strength of agreement was categorized as fair, moderate, good, and very good. RESULTS: A total of 6003 records were identified. After screening, 13 studies were included in our analysis. The overall interobserver agreement rates were 0.58 for eMS, 0.66 for UCEIS, 0.80 for CDEIS, and 0.78 for SES-CD. The overall heterogeneity (I2) for these systems ranged from 93.2% to 99.2%. A few studies assessed the intraobserver agreement rate. The overall effect sizes were 0.75 for eMS, 0.87 for UCEIS, 0.89 for CDEIS, and 0.91 for SES-CD. CONCLUSIONS: The interobserver agreement rates for eMS, UCEIS, CDEIS, and SES-CD ranged from moderate to good. The intraobserver agreement rates for eMS, UCEIS, CDEIS, and SES-CD ranged from good to very good. Solutions to improve interobserver agreement could allow for more accurate patient assessment, leading to richer, more accurate clinical management and clinical trial data.

This study examined the inter- and intraobserver variability of inflammatory bowel disease endoscopic scoring systems (endoscopic Mayo Score, Ulcerative Colitis Endoscopic Index of Severity, Crohn's Disease Endoscopic Index of Severity, Simple Endoscopic Score for Crohn's Disease) in a systematic review and meta-analysis.

Heterogeneity by age and gender in the association of kidney function with mortality among patients with diabetes - analysis of diabetes registry in Singapore.

BACKGROUND: We aimed to explore the three-way interaction among age, gender, and kidney function on the risk of all-cause mortality and cardiovascular mortality among patients with type 2 diabetes (T2D). METHODS: In a retrospective cohort study, patients aged > 40 years with T2D with serum creatinine and urine albumin measured from 2013 to 2019 were included from a multi-institutional diabetes registry. The exposure was estimated glomerular filtration rate (eGFR), outcomes were all-cause mortality (primary outcome) and cardiovascular disease (CVD) mortality (secondary outcome). We applied multivariable cox proportional hazards regression analysis to compute the association between eGFR and mortality. RESULTS: A total of 36,556 patients were followed for up to 6 years during which 2492 (6.82%) died from all causes, and 690 (1.9%) died from CVD. We observed a significant three-way interaction (p = 0.021) among age (younger, < 65; older, ≥65 years), gender and eGFR for the risk of all-cause mortality. Using age- and gender-specific eGFR of 90 ml/min/1.73m2 as the reference point, the adjusted hazard rate (HR) (95% CI) for all-cause mortality at eGFR of 40 ml/min/1.73m2 was 3.70 (2.29 to 5.99) in younger women and 1.86 (1.08 to 3.19) in younger men. The corresponding adjusted HRs in older women and older men were 2.38 (2.02 to 2.82) and 2.18 (1.85 to 2.57), respectively. Similar results were observed for CVD deaths, although the three-way interaction was not statistically significant. Sensitivity analysis yielded similar results. CONCLUSIONS: In this T2D population, younger women with reduced kidney function might be more susceptible to higher risks of all-cause mortality and CVD mortality than younger men.

Phytosterol intake and risk of coronary artery disease: Results from 3 prospective cohort studies.

BACKGROUND: Phytosterols are structurally similar to cholesterol and partially inhibit intestinal absorption of cholesterol, although their impact on coronary artery disease (CAD) risk remains to be elucidated. OBJECTIVES: This study aimed to prospectively assess the associations between total and individual phytosterol intake and CAD risk in United States health professionals. METHODS: The analysis included 213,992 participants from 3 prospective cohorts-the Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study-without cardiovascular disease or cancer at baseline. Diet was assessed using a validated food frequency questionnaire every 2-4 y since baseline. Associations between phytosterol intake and the risk of CAD, such as nonfatal myocardial infarction and fatal CAD, were evaluated using Cox proportional hazards regression models. RESULTS: More than 5,517,993 person-years, 8725 cases with CAD were documented. Comparing extreme quintiles, pooled hazard ratios (95% CIs) of CAD were 0.93 (0.86, 1.01; P-trend = 0.16) for total phytosterols, 0.89 (0.82, 0.96; P-trend = 0.05) for campesterol, 0.95 (0.88, 1.02; P-trend = 0.10) for stigmasterol, and 0.92 (0.85, 1.00; P-trend = 0.09) for ß-sitosterol. Nonlinear associations were observed for total phytosterols, campesterol, and ß-sitosterol: the risk reduction plateaued at intakes above ∼180, 30, and 130 mg/d, respectively (P-nonlinearity < 0.001). In a subset of participants (N range between 11,983 and 22,039), phytosterol intake was inversely associated with plasma concentrations of total cholesterol, triglycerides, high-density lipoprotein cholesterol, and IL-6 and positively associated with adiponectin, whereas no significant associations were observed for low-density lipoprotein cholesterol or C-reactive protein concentrations. CONCLUSIONS: Higher long-term intake of total and major subtypes of phytosterols may be associated with a modest reduction in CAD risk, displaying a nonlinear relationship that plateau at moderate intake levels. The role of phytosterols in preventing CAD warrants further investigation.

Associations between plant-based dietary patterns and risks of type 2 diabetes, cardiovascular disease, cancer, and mortality - a systematic review and meta-analysis.

BACKGROUND: Plant-based dietary patterns are gaining more attention due to their potential in reducing the risk of developing major chronic diseases, including type 2 diabetes (T2D), cardiovascular disease (CVD), cancer, and mortality, while an up-to-date comprehensive quantitative review is lacking. This study aimed to summarize the existing prospective observational evidence on associations between adherence to plant-based dietary patterns and chronic disease outcomes. METHODS: We conducted a systematic review and meta-analysis of evidence across prospective observational studies. The data sources used were PubMed and MEDLINE, Embase, Web of Science, and screening of references. We included all prospective observational studies that evaluated the association between adherence to plant-based dietary patterns and incidence of T2D, CVD, cancer, and mortality among adults (≥ 18 years). RESULTS: A total of 76 publications were identified, including 2,230,443 participants with 60,718 cases of incident T2D, 157,335 CVD cases, 57,759 cancer cases, and 174,435 deaths. An inverse association was observed between higher adherence to a plant-based dietary pattern and risks of T2D (RR, 0.82 [95% CI: 0.77-0.86]), CVD (0.90 [0.85-0.94]), cancer (0.91 [0.87-0.96]), and all-cause mortality (0.84 [0.78-0.92]) with moderate to high heterogeneity across studies (I2 ranged: 47.8-95.4%). The inverse associations with T2D, CVD and cancer were strengthened when healthy plant-based foods, such as vegetables, fruits, whole grains, and legumes, were emphasized in the definition of plant-based dietary patterns (T2D: 0.79 [0.72-0.87]; CVD: 0.85 [0.80-0.92]; cancer: 0.86 [0.80-0.92]; I2 ranged: 53.1-84.1%). Association for mortality was largely similar when the analyses were restricted to healthy plant-based diets (0.86 [0.80-0.92], I2 = 91.9%). In contrast, unhealthy plant-based diets were positively associated with these disease outcomes. Among four studies that examined changes in dietary patterns, increased adherence to plant-based dietary patterns was associated with a significantly reduced risk of T2D (0.83 [0.71-0.96]; I2 = 71.5%) and a marginally lower risk of mortality (0.95 [0.91-1.00]; I2 = 0%). CONCLUSIONS: Better adherence to plant-based dietary patterns, especially those emphasizing healthy plant-based foods, is beneficial for lowering the risks of major chronic conditions, including T2D, CVD, cancer, as well as premature deaths. REGISTRATION OF REVIEW PROTOCOL: This review was registered at the PROSPERO International Prospective Register of Systematic Reviews ( https://www.crd.york.ac.uk/PROSPERO/ ) with the registration number CRD42022290202.

Discordance Between Creatinine-Based and Cystatin C-Based Estimated GFR: Interpretation According to Performance Compared to Measured GFR.

Rationale & Objective: Use of cystatin C in addition to creatinine to estimate glomerular filtration rate (estimated glomerular filtration rate based on cystatin C [eGFRcys] and estimated glomerular filtration rate based on creatinine [eGFRcr], respectively) is increasing. When eGFRcr and eGFRcys are discordant, it is not known which is more accurate, leading to uncertainty in clinical decision making. Study Design: Cross-sectional analysis. Setting & Participants: Four thousand fifty participants with measured glomerular filtration rate (mGFR) from 12 studies in North America and Europe. Exposures: Serum creatinine and serum cystatin C. Outcomes: Performance of creatinine-based and cystatin C-based glomerular filtration rate estimating equations compared to mGFR. Analytical Approach: We evaluated the accuracy of eGFRcr, eGFRcys, and the combination (eGFRcr-cys) compared to mGFR according to the magnitude of the difference between eGFRcr and eGFRcys (eGFRdiff). We used CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations to estimate glomerular filtration rate. eGFRdiff was defined as eGFRcys minus eGFRcr and categorized as less than -15, -15 to <15, and ≥15 mL/min/1.73 m2 (negative, concordant, and positive groups, respectively). We compared bias (median of mGFR minus eGFR) and the percentage of eGFR within 30% of mGFR. Results: Thirty percent of participants had discordant eGFRdiff (21.0% and 9.6% negative and positive eGFRdiffs, respectively). In the concordant eGFRdiff group, all equations displayed similar accuracy. In the negative eGFRdiff groups, eGFRcr had a large overestimation of mGFR (-13.4 [-14.5 to -12.2] mL/min/1.73 m2) and eGFRcys had a large underestimation (9.9 [9.1-11.2] mL/min/1.73m2), with opposite results in the positive eGFRdiff group. In both negative and positive eGFRdiff groups, eGFRcr-cys was more accurate than either eGFRcr or eGFRcys. These results were largely consistent across age, sex, race, and body mass index. Limitations: Few participants with major comorbid conditions. Conclusions: Discordant eGFRcr and eGFRcys are common. eGFR using the combination of creatinine and cystatin C provides the most accurate estimates among persons with discordant eGFRcr or eGFRcys.

Endoscopist-Level and Procedure-Level Factors Associated With Increased Adenoma Detection With the Use of a Computer-Aided Detection Device.

INTRODUCTION: To investigate the impact of procedure-related and endoscopist-related factors on the effectiveness of a computer-aided detection (CADe) device in adenomas per colonoscopy (APC) detection. METHODS: The SKOUT clinical trial was conducted at 5 US sites. We present prespecified analyses of procedure-related and endoscopist-related factors, and association with APC across treatment and control cohorts. RESULTS: There were numeric increases in APC between SKOUT vs standard colonoscopy in community-based endoscopists, withdrawal time of ≥8 minutes, for endoscopists with >20 years of experience, and endoscopists with baseline adenoma detection rate <45%. DISCUSSION: The application of CADe devices in clinical practice should be carefully evaluated. Larger studies should explore differences in endoscopist-related factors for CADe.

Knowledge of COVID-19 and associated factors among kidney transplant recipients and donors in Singapore.

Background: Effective interventions during the coronavirus disease 2019 (COVID-19) pandemic require an understanding of patients' knowledge and perceptions that influence their behaviour. Our study assessed knowledge of COVID-19 among kidney transplant recipients and donors, hitherto unevaluated. Methods: We conducted a cross-sectional survey among 325 kidney transplant recipients and 172 donors between 1 May 2020 and 30 June 2020. The survey questionnaire assessed knowledge levels of COVID-19, sociodemographic data, health status, psychosocial impact of COVID-19 and precautionary behaviours during the pandemic. Results: The mean COVID-19 knowledge score of the study population was 7.5 (standard deviation: 2.2) out of 10. The mean score was significantly higher among kidney recipients compared to kidney donors (7.9 [1.9] vs. 6.7 [2.6]; P <0.001). Younger age (21-49 vs. ≥50 years) and higher education (diploma and higher vs. secondary and lower) were associated with significantly higher knowledge scores in donors, but not among recipients (P-interactions ≤0.01). In both kidney recipients and donors, financial concerns and/or social isolation were associated with lower knowledge levels. Conclusions: Concerted efforts are needed to improve COVID-19 knowledge in kidney transplant recipients and donors, particularly older donors, donors with lower education and patients with financial concerns or feelings of social isolation. Intensive patient education may mitigate the impact of education levels on COVID-19 knowledge levels.

Circ_0005615 Regulates the Progression of Colorectal Cancer Through the miR-873-5p/FOSL2 Signaling Pathway.

To determine the effects of circ_0005615 in CRC development and underneath mechanism. The expression levels of circ_0005615, microRNA-873-5p (miR-873-5p) and FOS-like antigen 2 (FOSL2) mRNA were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of exosome makers, proliferation-related makers and FOSL2 were detected by western blot or immunohistochemistry assay. Cell proliferation was evaluated by cell counting kit-8 (CCK-8) and cell colony formation assays. Cell migration and invasion were demonstrated by a transwell assay. Cell apoptosis was investigated by flow cytometry analysis. The binding relationship between miR-873-5p and circ_0005615 or FOSL2 was predicted by circular RNA interactome and targetscan online databases, respectively, and identified by dual-luciferase reporter assay. The impacts of circ_0005615 silencing on tumor formation were determined by in vivo tumor formation assay. Circ_0005615 expression was dramatically upregulated in serum exosomes of CRC patients compared with the control group. The CRC patients with a high circ_0005615 expression had a poor survival rate. Circ_0005615 and FOSL2 expressions were apparently increased, while miR-873-5p was decreased in CRC tissues or cells relative to control groups. Circ_0005615 knockdown inhibited cell proliferation, migration, and invasion, whereas promoted cell apoptosis in CRC; however, miR-873-5p inhibitor attenuated these impacts. Additionally, circ_0005615 acted as a sponge of miR-873-5p and miR-873-5p bound to FOSL2. FOSL2 overexpression restrained the effects of miR-873-5p mimic on CRC progression. Furthermore, circ_0005615 knockdown suppressed tumor growth in vivo. Circ_0005615 modulated CRC malignant progression by controlling FOSL2 expression through sponging miR-873-5p. This finding lays a foundation for the study on circRNA-mediated CRC therapy.

Urinary polycyclic aromatic hydrocarbon excretion and regional body fat distribution: evidence from the U.S. National Health and Nutrition Examination Survey 2001-2016.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that may contribute to the etiology of obesity. However, it is unclear whether PAHs from environmental sources are associated with regional body fat distribution, and whether the association varies across racial/ethnic groups who may have differential PAH exposure patterns. OBJECTIVES: To examine correlations between PAHs and body fat distribution, and potential racial/ethnic differences among U.S. adults. METHODS: Ten PAHs were measured in spot urine samples from 2691 non-smoking adults (age ≥ 20 years) in the NHANES 2001-2016. Dual-energy X-ray absorptiometry was used to measure fat mass percent (FM%). Partial Pearson correlation coefficients (r) with multivariable adjustment were used to assess PAH-FM% associations. RESULTS: In the total population, 1-naphthalene, 3-fluorene, and 1-pyrene were inversely correlated with total FM% or trunk FM% (adjusted r ranged: - 0.06 to - 0.08), while 2-naphthalene, 9-fluorene, and 4-phenanthrene were positively correlated with the FM% measurements (r: 0.07-0.11). PAH levels are highest among non-Hispanic Blacks, followed by Hispanics and Whites and some of the correlations were different by these races/ethnicities. Among non-Hispanic Whites, no PAH was correlated with FM%. In contrast, 9-fluorene was positively correlated with total FM% (r = 0.20) and trunk FM% (r = 0.22) among Blacks, and 4-phenanthrene was positively correlated with total FM% (r = 0.23) and trunk FM% (r = 0.24) among Hispanics (P-interaction: 0.010-0.025). DISCUSSION: In this US adult population, certain PAHs are significantly associated with higher body fat contents among non-Hispanic Blacks and Hispanics but not non-Hispanic Whites, suggesting that minority groups might be particularly susceptible to PAH's obesogenic effects or the effects of other factors that determine the PAH exposure levels. Alternatively, differences in body composition may contribute to differential PAH metabolism in minority groups. Future studies are warranted to explore the racial/ethnic disparity in PAH exposures, drivers of these exposure differences, and mechanisms through which PAHs may influence body composition by races/ethnicities.

Psychological distress and associated factors among kidney transplant recipients and living kidney donors during COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused significant psychological distress globally. Our study assessed the prevalence of psychological distress and associated factors during COVID-19 pandemic among kidney transplant recipients and kidney donors. METHODS: A cross-sectional survey of 497 participants (325 recipients and 172 donors) was conducted from 1st May to 30th June 2020 in Singapore. The survey questionnaire assessed knowledge levels of COVID-19, socio-demographic data, health status, psychosocial impact of COVID-19, and precautionary behaviors during the pandemic. Psychological distress was defined as having anxiety, depression, or stress measured by the validated Depression, Anxiety and Stress Scale-21. Linear regression analyses were used to assess factors associated with higher psychological distress. RESULTS: The prevalence of psychological distress was 14.3% (95% confidence interval: 11.5-17.6%) in the overall population; it was 12.8% (9.79-16.6%) in recipients and 13.4% (9.08-19.6%) in donors with no significant difference (P = 0.67). Younger age (21-49 vs. ≥50 years), unmarried status, non-Singapore citizen, worse health conditions, and worrying about physical and mental health were associated with higher psychological distress. Malays (versus Chinese), taking precautionary measures (hand sanitization), and receiving enough information about COVID-19 were associated with lower psychological distress. No interactions were observed between recipients and donors. CONCLUSIONS: At least one in ten recipients and donors suffer from psychological distress during COVID-19 pandemic. Focused health education to younger adults, unmarried individuals, non-Singapore citizens, and those with poor health status could potentially prevent psychological distress in recipients and donors.

Chronic kidney disease biomarkers and mortality among older adults: A comparison study of survey samples in China and the United States.

OBJECTIVES: Among older adults in China and the US, we aimed to compare the biomarkers of chronic-kidney-diseases (CKD), factors associated with CKD, and the correlation between CKD and mortality. SETTING: China and the US. STUDY DESIGN: Cross-sectional and prospective cohorts. PARTICIPANTS: We included 2019 participants aged 65 and above from the Chinese Longitudinal Healthy Longevity Study (CLHLS) in 2012, and 2177 from US National Health and Nutrition Examination Survey (NHANES) in 2011-2014. OUTCOMES: Urinary albumin, urinary creatinine, albumin creatinine ratio (ACR), serum creatinine, blood urea nitrogen, plasma albumin, uric acid, and estimated glomerular filtration rate (eGFR). CKD (ACR ≥ 30 mg/g or eGFR< 60 ml/min/1.73m2) and mortality. ANALYTICAL APPROACH: Logistic regression and Cox proportional hazard models. Covariates included age, sex, race, education, income, marital status, health condition, smoking and drinking status, physical activity and body mass index. RESULTS: Chinese participants had lower levels of urinary albumin, ACR, and uric acid than the US (mean: 25.0 vs 76.4 mg/L, 41.7 vs 85.0 mg/g, 292.9 vs 341.3 µmol/L). In the fully-adjusted model, CKD was associated with the risk of mortality only in the US group (hazard ratio [HR], 95% CI: 2.179, 1.561-3.041 in NHANES, 1.091, 0.940-1.266 in CLHLS). Compared to eGFR≥90, eGFR ranged 30-44 ml/min/1.73m2 was only associated with mortality in the US population (HR, 95% CI: 2.249, 1.141-4.430), but not in the Chinese population (HR, 95% CI: 1.408, 0.884-2.241). CONCLUSIONS: The elderly participants in the US sample had worse CKD-related biomarker levels than in China sample, and the association between CKD and mortality was also stronger among the US older adults. This may be due to the biological differences, or co-morbid conditions.

Ethnic variation, socioeconomic status, and factors associated with cardio-metabolic multi-morbidity among uncontrolled hypertension in multiethnic Singapore.

Identifying patients with hypertension at high risk of cardio-metabolic multi-morbidity (CMM) is key for intervention. We examined the independent association of CMM with ethnicity and socioeconomic status (SES) among patients with uncontrolled hypertension. Demographic, socioeconomic, lifestyle, and clinical factors were obtained from 921 patients aged ≥40 years with hypertension in the multiethnic Singapore. CMM was defined as having ≥2 chronic diseases (diabetes mellitus, heart disease, stroke, and chronic kidney disease), which were confirmed by medical records or laboratory measurements. The overall CMM prevalence was 20.9% (95% confidence interval [CI]: 18.4-23.6%). The CMM prevalence was higher in Malays (27.1%) and Indians (30.2%) than Chinese (18.8%), and it was higher among patients with lower SES (ranging from 21.3 to 23.9% using education, employment status, housing ownership and housing types as proxies) compared to those with higher SES (13.1-20.8%). In a multivariate model comprising demographic and socioeconomic factors (age, sex, ethnicity and SES), higher CMM odds were independently associated with ethnic minorities (Malays [OR 1.81; 95% CI: 1.10-2.98] or Indians [OR 2.21; 95% CI: 1.49-3.29] vs. Chinese) and lower SES (unemployment [OR 1.45; 95% CI: 1.02-2.05] and residing in smaller public housing [OR 1.95; 95% CI: 1.16-3.28]). Other correlates of CMM included age, men, central obesity, and poorer dietary quality (lower fruits and vegetables intakes). CMM affected one out of five patients with hypertension in Singapore. Intervention programs should target patients with hypertension, particularly those of ethnic minorities and from lower socioeconomic strata.

Whole Brain Mapping of Neurons Innervating Extraorbital Lacrimal Glands in Mice and Rats of Both Genders.

The extraorbital lacrimal glands (ELGs) secret tears to maintain a homeostatic environment for ocular surfaces, and pheromones to mediate social interactions. Although its distinct gender-related differences in mice and rats have been identified, its comprehensive histology together with whole-brain neuronal network remain largely unknown. The primary objective of the present study was to investigate whether sex-specific differences take place in histological and physiological perspectives. Morphological and histological data were obtained via magnetic resonance imaging (MRI), hematoxylin-eosin (HE) staining in mice and rats of both genders. The innervating network was visualized by a pseudorabies virus (PRV) mediated retrograde trans-multi-synaptic tracing system for adult C57BL6/J mice of both genders. In terms of ELGs' anatomy, mice and rats across genders both have 7 main lobes, with one exception observed in female rats which have only 5 lobes. Both female rats and mice generally have relatively smaller shape size, absolute weight, and cell size than males. Our viral tracing revealed a similar trend of innervating patterns antero-posteriorly, but significant gender differences were also observed in the hypothalamus (HY), olfactory areas (OLF), and striatum (STR). Brain regions including piriform area (Pir), post-piriform transition area (TR), central amygdalar nucleus (CEA), medial amygdalar nucleus (MEA), lateral hypothalamic area (LHA), parasubthalamic nucleus (PSTN), pontin reticular nucleus (caudal part) (PRNc), and parabrachial nucleus, (PB) were commonly labeled. In addition, chemical isotope labeling-assisted liquid chromatography-mass spectrometry (CIL-LC-MS) and nuclear magnetic resonance spectroscopy (NMR spectroscopy) were performed to reveal the fatty acids and metabolism of the ELGs, reflecting the relationship between pheromone secretion and brain network. Overall, our results revealed basic properties and the input neural networks for ELGs in both genders of mice, providing a structural basis to analyze the diverse functions of ELGs.

Socioeconomic status and ethnic variation associated with type 2 diabetes mellitus in patients with uncontrolled hypertension in Singapore.

INTRODUCTION: The burden of type 2 diabetes mellitus (T2DM) and related vascular complications is particularly high in Asians and ethnic minorities living in the West. However, the association of T2DM with socioeconomic status (SES) and ethnicity has not been widely studied in populations living in Asia. Therefore, we investigated these associations among the multiethnic population with uncontrolled hypertension in Singapore. RESEARCH DESIGN AND METHODS: In a cross-sectional study using baseline data of a 2-year randomized trial in Singapore, we obtained demographic, SES, lifestyle and clinical factors from 915 patients aged ≥40 years with uncontrolled hypertension. T2DM was defined as having either: (i) self-reported 'physician-diagnosed diabetes confirmed through medical records' or taking antidiabetes medications, (ii) fasting blood glucose levels ≥7.0 mmol/dL or (iii) hemoglobin A1c ≥6.5%. The SES proxies included education, employment status, housing ownership and housing type, and the ethnicities were Chinese, Malays and Indians. Logistic regression analyses were used to evaluate the association of T2DM with SES and ethnicity. RESULTS: Higher proportion of T2DM was observed in Malays (40.0%) and Indians (56.0%) than Chinese (26.8%) (p<0.001), and in patients with lower SES (ranging from 25.7% to 66.2% using different proxies) than those with higher SES (19.4% to 32.0%). In a multivariate model comprising age, gender, ethnicity and SES, Malay ethnicity (OR 1.59; 95% CI 1.04 to 2.44, p=0.031) or Indian ethnicity (OR 3.65; 95% CI 2.25 to 5.91, p<0.001) versus Chinese and housing type (residing in one to three rooms (OR 2.00; 95% CI 1.16 to 3.43, p=0.012) or four to five rooms public housing (OR 1.86; 95% CI 1.13 to 3.04, p=0.013) vs private housing) were associated with higher T2DM odds. The associations of Indians and one to three rooms public housing with T2DM met the significance after accounting for multiple testing (p≤0.0125). CONCLUSION: Our study suggests that housing type and ethnic variation are independently associated with higher T2DM risk in patients with uncontrolled hypertension in Singapore. Further studies are needed to validate our results. TRIAL REGISTRATION NUMBER: NCT02972619.

Formononetin/methyl-ß-cyclodextrin inclusion complex incorporated into electrospun polyvinyl-alcohol nanofibers: Enhanced water solubility and oral fast-dissolving property.

Improving solubility and administration route of isoflavone formononetin (FMN) are critical factors to improve its bioavailability in the oral cavity. This study fabricated fast-dissolving nanofibers containing FMN/methyl-ß-cyclodextrin (FMN/Me-ß-CD) inclusion complex. The solubility of FMN could be increased by approximately 50 times at 20 mM aqueous Me-ß-CD. Interactions and thermodynamic parameters of the host-guest inclusion complex were studied by a fluorescence quenching method. The structure and mechanisms of the complex were further studied by molecular docking and molecular dynamics. Finally, polyvinyl-alcohol (PVA) nanofibrous webs containing the FMN/Me-ß-CD inclusion complex were fabricated by electrospinning. The dissolution test demonstrated that the FMN/Me-ß-CD/PVA nanofibers can be dissolved in artificial saliva within approximately 2 s. This study shows the potential of Me-ß-CD inclusion and electrospinning to improve solubility and administration route of isoflavones.

Performance and Determinants of Serum Creatinine and Cystatin C-Based GFR Estimating Equations in South Asians.

INTRODUCTION: The creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) equation was calibrated for the general Pakistan population (eGFRcr-PK) to eliminate bias and improve accuracy. Cystatin C-based CKD-EPI equations (eGFRcys and eGFRcr-cys) have not been assessed in this population, and non-GFR determinants of cystatin C are unknown. METHODS: We assessed eGFRcys, eGFRcr-cys, and non-GFR determinants of cystatin C in a cross-sectional study of 557 participants (≥40 years of age) from Pakistan. We compared bias (median difference in measured GFR [mGFR] and eGFR), precision (interquartile range [IQR] of differences), accuracy (percentage of eGFR within 30% of mGFR), root mean square error (RMSE), and classification of mGFR <60 ml/min/1.73 m2 (area under the receiver operating characteristic curve [AUC] and net reclassification index [NRI]) among eGFR equations. RESULTS: We found that eGFRcys underestimated mGFR (bias, 12.7 ml/min/1.73 m2 [95% confidence interval {CI} 10.7-15.2]). eGFRcr-cys did not improve performance over eGFRcr-PK in precision (P = 0.52), accuracy (P = 0.58), or RMSE (P = 0.49). Results were consistent among subgroups by age, sex, smoking, body mass index (BMI), and eGFR. NRI was 7.31% (95% CI 1.52%-13.1%; P < 0.001) for eGFRcr-cys versus eGFRcr-PK, but AUC was not improved (0.92 [95% CI 0.87-0.96] vs. 0.90 [95% CI 0.86-0.95]; P = 0.056). Non-GFR determinants of higher cystatin C included male sex, smoking, higher BMI and total body fat, and lower lean body mass. CONCLUSION: eGFRcys underestimated mGFR in South Asians and eGFRcr-cys did not offer substantial advantage compared with eGFRcr-PK. Future studies are warranted to better understand the large bias in eGFRcys and non-GFR determinants of cystatin C in South Asians.