Circulating metabolomic markers linking diabetic kidney disease and incident cardiovascular disease in type 2 diabetes: analyses from the Hong Kong Diabetes Biobank.

AIMS/HYPOTHESIS: The aim of this study was to describe the metabolome in diabetic kidney disease (DKD) and its association with incident CVD in type 2 diabetes, and identify prognostic biomarkers. METHODS: From a prospective cohort of individuals with type 2 diabetes, baseline sera (N=1991) were quantified for 170 metabolites using NMR spectroscopy with median 5.2 years of follow-up. Associations of chronic kidney disease (CKD, eGFR<60 ml/min per 1.73 m2) or severely increased albuminuria with each metabolite were examined using linear regression, adjusted for confounders and multiplicity. Associations between DKD (CKD or severely increased albuminuria)-related metabolites and incident CVD were examined using Cox regressions. Metabolomic biomarkers were identified and assessed for CVD prediction and replicated in two independent cohorts. RESULTS: At false discovery rate (FDR)<0.05, 156 metabolites were associated with DKD (151 for CKD and 128 for severely increased albuminuria), including apolipoprotein B-containing lipoproteins, HDL, fatty acids, phenylalanine, tyrosine, albumin and glycoprotein acetyls. Over 5.2 years of follow-up, 75 metabolites were associated with incident CVD at FDR<0.05. A model comprising age, sex and three metabolites (albumin, triglycerides in large HDL and phospholipids in small LDL) performed comparably to conventional risk factors (C statistic 0.765 vs 0.762, p=0.893) and adding the three metabolites further improved CVD prediction (C statistic from 0.762 to 0.797, p=0.014) and improved discrimination and reclassification. The 3-metabolite score was validated in independent Chinese and Dutch cohorts. CONCLUSIONS/INTERPRETATION: Altered metabolomic signatures in DKD are associated with incident CVD and improve CVD risk stratification.

Facile Preparation of Carbon Nanotubes/Cellulose Nanofibrils/Manganese Dioxide Nanowires Electrode for Improved Solid-Sate Supercapacitor Performances.

Wearable energy storage devices require high mechanical stability and high-capacitance flexible electrodes. In this study, we design a flexible supercapacitor electrode consisting of 1-dimensional carbon nanotubes (CNT), cellulose nanofibrils (CNF), and manganese dioxide nanowires (MnO2 NWs). The flexible and conductive CNT/CNF-MnO2 NWs suspension was first prepared via ultrasonic dispersion approach, followed by vacuum filtration and hot press to form the composite paper electrode. The morphological studies show entanglement between CNT and CNF, which supports the mechanical properties of the composite. The CNT/CNF-MnO2 NWs electrode exhibits lower resistance when subjected to various bending angles (-120-+120°) compared to the CNT/CNF electrode. In addition, the solid-state supercapacitor also shows a high energy density of 38 µWh cm-2 and capacitance retention of 83.2% after 5000 cycles.

Identification of a Common Variant for Coronary Heart Disease at PDE1A Contributes to Individualized Treatment Goals and Risk Stratification of Cardiovascular Complications in Chinese Patients With Type 2 Diabetes.

OBJECTIVE: In this study we aim to unravel genetic determinants of coronary heart disease (CHD) in type 2 diabetes (T2D) and explore their applications. RESEARCH DESIGN AND METHODS: We performed a two-stage genome-wide association study for CHD in Chinese patients with T2D (3,596 case and 8,898 control subjects), followed by replications in European patients with T2D (764 case and 4,276 control subjects) and general populations (n = 51,442-547,261). Each identified variant was examined for its association with a wide range of phenotypes and its interactions with glycemic, blood pressure (BP), and lipid controls in incident cardiovascular diseases. RESULTS: We identified a novel variant (rs10171703) for CHD (odds ratio 1.21 [95% CI 1.13-1.30]; P = 2.4 × 10-8) and BP (ß ± SE 0.130 ± 0.017; P = 4.1 × 10-14) at PDE1A in Chinese T2D patients but found only a modest association with CHD in general populations. This variant modulated the effects of BP goal attainment (130/80 mmHg) on CHD (Pinteraction = 0.0155) and myocardial infarction (MI) (Pinteraction = 5.1 × 10-4). Patients with CC genotype of rs10171703 had >40% reduction in either cardiovascular events in response to BP control (2.9 × 10-8 < P < 3.6 × 10-5), those with CT genotype had no difference (0.0726 < P < 0.2614), and those with TT genotype had a threefold increase in MI risk (P = 6.7 × 10-3). CONCLUSIONS: We discovered a novel CHD- and BP-related variant at PDE1A that interacted with BP goal attainment with divergent effects on CHD risk in Chinese patients with T2D. Incorporating this information may facilitate individualized treatment strategies for precision care in diabetes, only when our findings are validated.

Altered human gut virome in patients undergoing antibiotics therapy for Helicobacter pylori.

Transient gut microbiota alterations have been reported after antibiotic therapy for Helicobacter pylori. However, alteration in the gut virome after H. pylori eradication remains uncertain. Here, we apply metagenomic sequencing to fecal samples of 44 H. pylori-infected patients at baseline, 6-week (N = 44), and 6-month (N = 33) after treatment. Following H. pylori eradication, we discover contraction of the gut virome diversity, separation of virome community with increased community difference, and shifting towards a higher proportion of core virus. While the gut microbiota is altered at 6-week and restored at 6-month, the virome community shows contraction till 6-month after the treatment with enhanced phage-bacteria interactions at 6-week. Multiple courses of antibiotic treatments further lead to lower virus community diversity when compared with treatment naive patients. Our results demonstrate that H. pylori eradication therapies not only result in transient alteration in gut microbiota but also significantly alter the previously less known gut virome community.

Chitosan-Bead-Encapsulated Polystyrene Sulfonate for Adsorption of Methylene Blue and Regeneration Studies: Batch and Continuous Approaches.

Textile industrialization causes water pollution due to the discharge of industrial effluents into the environment. To reduce the impact of industrial effluent, it must be treated in wastewater treatment plants before discharge into rivers. Among all wastewater treatment approaches, the adsorption process is one method to remove pollutants from wastewater, but it has some limitations in term of reusability and ionic selective adsorption properties. In this study, we prepared cationic poly (styrene sulfonate) (PSS)-incorporated anionic chitosan beads synthesized using the oil-water emulsion coagulation method. The produced beads were characterized using FESEM and FTIR analysis. In batch adsorption studies, the PSS-incorporated chitosan beads exhibited monolayer adsorption processes, that is, exothermic processes that occur spontaneously at low temperatures, which were analyzed based on the adsorption isotherms, adsorption kinetics, and thermodynamics model fittings. The presence of PSS enables cationic methylene blue dye to adsorb to the anionic chitosan structure via electrostatic interaction between the sulfonic group and the dye molecule. The maximum adsorption capacity of PSS-incorporated chitosan beads achieved 42.21 mg/g, as calculated from the Langmuir adsorption isotherm. Finally, the PSS-incorporated chitosan beads demonstrated good regeneration with different types of reagents, especially using sodium hydroxide as a regeneration reagent. With the use of sodium hydroxide regeneration of this adsorbent material, a continuous adsorption setup also demonstrated that PSS-incorporated chitosan beads can be reused for methylene blue adsorption for up to three cycle processes.

High-density lipoprotein subclasses and cardiovascular disease and mortality in type 2 diabetes: analysis from the Hong Kong Diabetes Biobank.

OBJECTIVE: High-density lipoproteins (HDL) comprise particles of different size, density and composition and their vasoprotective functions may differ. Diabetes modifies the composition and function of HDL. We assessed associations of HDL size-based subclasses with incident cardiovascular disease (CVD) and mortality and their prognostic utility. RESEARCH DESIGN AND METHODS: HDL subclasses by nuclear magnetic resonance spectroscopy were determined in sera from 1991 fasted adults with type 2 diabetes (T2D) consecutively recruited from March 2014 to February 2015 in Hong Kong. HDL was divided into small, medium, large and very large subclasses. Associations (per SD increment) with outcomes were evaluated using multivariate Cox proportional hazards models. C-statistic, integrated discrimination index (IDI), and categorial and continuous net reclassification improvement (NRI) were used to assess predictive value. RESULTS: Over median (IQR) 5.2 (5.0-5.4) years, 125 participants developed incident CVD and 90 participants died. Small HDL particles (HDL-P) were inversely associated with incident CVD [hazard ratio (HR) 0.65 (95% CI 0.52, 0.81)] and all-cause mortality [0.47 (0.38, 0.59)] (false discovery rate < 0.05). Very large HDL-P were positively associated with all-cause mortality [1.75 (1.19, 2.58)]. Small HDL-P improved prediction of mortality [C-statistic 0.034 (0.013, 0.055), IDI 0.052 (0.014, 0.103), categorical NRI 0.156 (0.006, 0.252), and continuous NRI 0.571 (0.246, 0.851)] and CVD [IDI 0.017 (0.003, 0.038) and continuous NRI 0.282 (0.088, 0.486)] over the RECODe model. CONCLUSION: Small HDL-P were inversely associated with incident CVD and all-cause mortality and improved risk stratification for adverse outcomes in people with T2D. HDL-P may be used as markers for residual risk in people with T2D.

Chitosan Fibers Loaded with Limonite as a Catalyst for the Decolorization of Methylene Blue via a Persulfate-Based Advanced Oxidation Process.

Wastewater generated from industries seriously impacts the environment. Conventional biological and physiochemical treatment methods for wastewater containing organic molecules have some limitations. Therefore, identifying other alternative methods or processes that are more suitable to degrade organic molecules and lower chemical oxygen demand (COD) in wastewater is necessary. Heterogeneous Fenton processes and persulfate (PS) oxidation are advanced oxidation processes (AOPs) that degrade organic pollutants via reactive radical species. Therefore, in this study, limonite powder was incorporated into porous regenerated chitosan fibers and further used as a heterogeneous catalyst to decompose methylene blue (MB) via sulfate radical-based AOPs. Limonite was used as a heterogeneous catalyst in this process to generate the persulfate radicals (SO4-·) that initiate the decolorization process. Limonite-chitosan fibers were produced to effectively recover the limonite powder so that the catalyst can be reused repeatedly. The formation of limonite-chitosan fibers viewed under a field emission scanning electron microscope (FESEM) showed that the limonite powder was well distributed in both the surface and cross-section area. The effectiveness of limonite-chitosan fibers as a catalyst under PS activation achieved an MB decolorization of 78% after 14 min. The stability and reusability of chitosan-limonite fibers were evaluated and measured in cycles 1 to 10 under optimal conditions. After 10 cycles of repeated use, the limonite-chitosan fiber maintained its performance up to 86%, revealing that limonite-containing chitosan fibers are a promising reusable catalyst material.

Biogenic Synthesis of Copper-Based Nanomaterials Using Plant Extracts and Their Applications: Current and Future Directions.

Plants have been used for multiple purposes over thousands of years in various applications such as traditional Chinese medicine and Ayurveda. More recently, the special properties of phytochemicals within plant extracts have spurred researchers to pursue interdisciplinary studies uniting nanotechnology and biotechnology. Plant-mediated green synthesis of nanomaterials utilises the phytochemicals in plant extracts to produce nanomaterials. Previous publications have demonstrated that diverse types of nanomaterials can be produced from extracts of numerous plant components. This review aims to cover in detail the use of plant extracts to produce copper (Cu)-based nanomaterials, along with their robust applications. The working principles of plant-mediated Cu-based nanomaterials in biomedical and environmental applications are also addressed. In addition, it discusses potential biotechnological solutions and new applications and research directions concerning plant-mediated Cu-based nanomaterials that are yet to be discovered so as to realise the full potential of the plant-mediated green synthesis of nanomaterials in industrial-scale production and wider applications. This review provides readers with comprehensive information, guidance, and future research directions concerning: (1) plant extraction, (2) plant-mediated synthesis of Cu-based nanomaterials, (3) the applications of plant-mediated Cu-based nanomaterials in biomedical and environmental remediation, and (4) future research directions in this area.

The impact of antenatal massage practice on intrapartum massage application and their associations with the use of analgesics during labour : Sub-analysis of a randomised control trial.

BACKGROUND: Massage during labour is one form of intrapartum non-pharmacological pain relief but it is not known whether the frequency of practicing these massage techniques among couples during the antenatal period could enhance the effectiveness of intrapartum massage. This study was to evaluate the association between compliance of antenatal massage practice with intrapartum application and their impact on the use of analgesics during labour. METHODS: This was a sub-analysis of a childbirth massage programme which was carried out in two public hospitals with total births of around 8000 per year. Data from women who were randomized to the massage group were further analysed. After attending the pre-birth training class on massage at 36 weeks gestation, couples would be encouraged to practice at home. Their compliance with massage at home was classified as good if they had practiced for at least 15 minutes for three or more days in a week, or as poor if the three-day threshold had not been reached. Application of intrapartum massage was quantified by the duration of practice divided by the total duration of the first stage of labour. Women's application of intrapartum massage were then divided into above and below median levels according to percentage of practice. Logistic regression was used to assess the use of epidural analgesia or pethidine, adjusted for duration of labour and gestational age when attending the massage class. RESULTS: Among the 212 women included, 103 women (48.6%) achieved good home massage compliance. No significant difference in the maternal characteristics or birth outcomes was observed between the good and poor compliance groups. The intrapartum massage application (median 21.1%) was inversely associated with duration of first stage of labour and positively associated with better home massage practice compliance (p = 0.04). Lower use of pethidine or epidural analgesia (OR 0.33 95% CI 0.12, 0.90) was associated with above median intrapartum massage application but not antenatal massage compliance, adjusted for duration of first stage of labour. CONCLUSIONS: More frequent practice of massage techniques among couples during antenatal period could enhance the intrapartum massage application, which may reduce the use of pethidine and epidural analgesia. TRIAL REGISTRATION: (CCRBCTR) Unique Trial Number CUHK_ CCRB00525 .

Nonalbuminuric Diabetic Kidney Disease and Risk of All-Cause Mortality and Cardiovascular and Kidney Outcomes in Type 2 Diabetes: Findings From the Hong Kong Diabetes Biobank.

RATIONALE & OBJECTIVE: Nonalbuminuric diabetic kidney disease (DKD) has become the prevailing DKD phenotype. We compared the risks of adverse outcomes among patients with this phenotype compared with other DKD phenotypes. STUDY DESIGN: Multicenter prospective cohort study. SETTINGS & PARTICIPANTS: 19,025 Chinese adults with type 2 diabetes enrolled in the Hong Kong Diabetes Biobank. EXPOSURES: DKD phenotypes defined by baseline estimated glomerular filtration rate (eGFR) and albuminuria: no DKD (no decreased eGFR or albuminuria), albuminuria without decreased eGFR, decreased eGFR without albuminuria, and albuminuria with decreased eGFR. OUTCOMES: All-cause mortality, cardiovascular disease (CVD) events, hospitalization for heart failure (HF), and chronic kidney disease (CKD) progression (incident kidney failure or sustained eGFR reduction ≥40%). ANALYTICAL APPROACH: Multivariable Cox proportional or cause-specific hazards models to estimate the relative risks of death, CVD, hospitalization for HF, and CKD progression. Multiple imputation was used for missing covariates. RESULTS: Mean participant age was 61.1 years, 58.3% were male, and mean diabetes duration was 11.1 years. During 54,260 person-years of follow-up, 438 deaths, 1,076 CVD events, 298 hospitalizations for HF, and 1,161 episodes of CKD progression occurred. Compared with the no-DKD subgroup, the subgroup with decreased eGFR without albuminuria had higher risks of all-cause mortality (hazard ratio [HR], 1.59 [95% CI, 1.04-2.44]), hospitalization for HF (HR, 3.08 [95% CI, 1.82-5.21]), and CKD progression (HR, 2.37 [95% CI, 1.63-3.43]), but the risk of CVD was not significantly greater (HR, 1.14 [95% CI, 0.88-1.48]). The risks of death, CVD, hospitalization for HF, and CKD progression were higher in the setting of albuminuria with or without decreased eGFR. A sensitivity analysis that excluded participants with baseline eGFR <30 mL/min/1.73 m2 yielded similar findings. LIMITATIONS: Potential misclassification because of drug use. CONCLUSIONS: Nonalbuminuric DKD was associated with higher risks of hospitalization for HF and of CKD progression than no DKD, regardless of baseline eGFR.

Clinical Predictors and Long-term Impact of Acute Kidney Injury on Progression of Diabetic Kidney Disease in Chinese Patients With Type 2 Diabetes.

We aim to assess the long-term impact of acute kidney injury (AKI) on progression of diabetic kidney disease (DKD) and all-cause mortality and investigate determinants of AKI in Chinese patients with type 2 diabetes (T2D). A consecutive cohort of 9,096 Chinese patients with T2D from the Hong Kong Diabetes Register was followed for 12 years (mean ± SD age 57 ± 13.2 years; 46.9% men; median duration of diabetes 5 years). AKI was defined based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria using serum creatinine. Estimated glomerular filtration rate measurements were used to identify the first episode with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Polygenic risk score (PRS) composed of 27 single nucleotide polymorphisms (SNPs) known to be associated with serum uric acid (SUA) in European populations was used to examine the role of SUA in pathogenesis of AKI, CKD, and ESRD. Validation was sought in an independent cohort including 6,007 patients (age 61.2 ± 10.9 years; 59.5% men; median duration of diabetes 10 years). Patients with AKI had a higher risk for developing incident CKD (hazard ratio 14.3 [95% CI 12.69-16.11]), for developing ESRD (12.1 [10.74-13.62]), and for all-cause death (7.99 [7.31-8.74]) compared with those without AKI. Incidence rate for ESRD among patients with no episodes of AKI and one, two, and three or more episodes of AKI was 7.1, 24.4, 32.4, and 37.3 per 1,000 person-years, respectively. Baseline SUA was a strong independent predictor for AKI. A PRS composed of 27 SUA-related SNPs was associated with AKI and CKD in both discovery and replication cohorts but not ESRD. Elevated SUA may increase the risk of DKD through increasing AKI. The identification of SUA as a modifiable risk factor and PRS as a nonmodifiable risk factor may facilitate the identification of individuals at high risk to prevent AKI and its long-term impact in T2D.

Application of droplet digital polymerase chain reaction of plasma methylated septin 9 on detection and early monitoring of colorectal cancer.

Methylated septin 9 (SEPT9) has been approved for non-invasive screening of colorectal cancer (CRC), but data on monitoring of CRC is sparse. Droplet digital polymerase chain reaction (ddPCR), with higher detection precision and simpler quantification than conventional PCR, has not been applied in SEPT9 detection. We explored the role of SEPT9 ddPCR for CRC detection and to measure serial SEPT9 levels in blood samples of CRC patients before and 3-month after surgery. SEPT9 methylated ratio, methylated abundance, and CEA levels were all higher in CRC patients than normal controls (all P < 0.05). The area under the curve (AUC) for methylated ratio and abundance to detect CRC was 0.707 and 0.710, respectively. There was an increasing trend for SEPT9 methylated abundance from proximal to distal cancers (P = 0.017). At 3-month after surgery, both methylated abundance and ratio decreased (P = 0.005 and 0.053, respectively), especially methylated abundance in stage III and distal cancer (both P < 0.01). We have developed a ddPCR platform for the quantitative detection of plasma SEPT9 in CRC patients. SEPT9 methylated abundance had an early post-operative decline, which may be useful in monitoring of treatment response.

A comparative analysis between low-dose-rate brachytherapy and external beam radiation therapy for low- and intermediate-risk prostate cancer in Asian men.

OBJECTIVE: To report the long-term clinical outcomes of low-risk (LR) and intermediate-risk (IR) prostate cancer patients treated with low-dose-rate brachytherapy (LDR-BT) and external beam radiation therapy (EBRT). PATIENTS AND METHODS: Men with biopsy-proven low- and intermediate-risk prostate cancer received EBRT and LDR-BT in an Asian academic center from 2000 to 2019 were reviewed. Kaplan-Meier survival analysis was performed to compare biochemical failure-free survival (bFFS) and overall survival (OS) between LDR and EBRT in the low- and intermediate-risk cohorts. RESULTS: 642 patients (521 EBRT and 121 LDR-BT) with low- and intermediate-risk prostate cancer were included for analysis. In the intermediate-risk group, 5- and 10-year bFFS was 96%, 89% and 86%, 61% for LDR-BT and EBRT, respectively. LDR-BT was associated with a statistically significant improvement of bFFS in the intermediate-risk cohort (HR 2.7, p = 0.02). In the low-risk cohort, no difference of bFFS was found between LDR-BT and EBRT (HR 1.9, p = 0.08). Hormone therapy was more common in EBRT than LDR-BT for intermediate-risk group (71% versus 44%, p < 0.05). Prostate cancer-specific mortality was low in both EBRT (1%) and LDR-BT (2%) cohorts. No significant difference in OS was found between LDR-BT and EBRT in low- and intermediate-risk group (HR 2.1, p = 0.2 and HR = 1.7, p = 0.3). CONCLUSION: In our retrospective study, LDR-BT is associated with superior bFFS compared with EBRT in Asian men with intermediate-risk prostate cancer.

Development of genome-wide polygenic risk scores for lipid traits and clinical applications for dyslipidemia, subclinical atherosclerosis, and diabetes cardiovascular complications among East Asians.

BACKGROUND: The clinical utility of personal genomic information in identifying individuals at increased risks for dyslipidemia and cardiovascular diseases remains unclear. METHODS: We used data from Biobank Japan (n = 70,657-128,305) and developed novel East Asian-specific genome-wide polygenic risk scores (PRSs) for four lipid traits. We validated (n = 4271) and subsequently tested associations of these scores with 3-year lipid changes in adolescents (n = 620), carotid intima-media thickness (cIMT) in adult women (n = 781), dyslipidemia (n = 7723), and coronary heart disease (CHD) (n = 2374 cases and 6246 controls) in type 2 diabetes (T2D) patients. RESULTS: Our PRSs aggregating 84-549 genetic variants (0.251 < correlation coefficients (r) < 0.272) had comparably stronger association with lipid variations than the typical PRSs derived based on the genome-wide significant variants (0.089 < r < 0.240). Our PRSs were robustly associated with their corresponding lipid levels (7.5 × 10- 103 < P < 1.3 × 10- 75) and 3-year lipid changes (1.4 × 10- 6 < P < 0.0130) which started to emerge in childhood and adolescence. With the adjustments for principal components (PCs), sex, age, and body mass index, there was an elevation of 5.3% in TC (ß ± SE = 0.052 ± 0.002), 11.7% in TG (ß ± SE = 0.111 ± 0.006), 5.8% in HDL-C (ß ± SE = 0.057 ± 0.003), and 8.4% in LDL-C (ß ± SE = 0.081 ± 0.004) per one standard deviation increase in the corresponding PRS. However, their predictive power was attenuated in T2D patients (0.183 < r < 0.231). When we included each PRS (for TC, TG, and LDL-C) in addition to the clinical factors and PCs, the AUC for dyslipidemia was significantly increased by 0.032-0.057 in the general population (7.5 × 10- 3 < P < 0.0400) and 0.029-0.069 in T2D patients (2.1 × 10- 10 < P < 0.0428). Moreover, the quintile of TC-related PRS was moderately associated with cIMT in adult women (ß ± SE = 0.011 ± 0.005, Ptrend = 0.0182). Independent of conventional risk factors, the quintile of PRSs for TC [OR (95% CI) = 1.07 (1.03-1.11)], TG [OR (95% CI) = 1.05 (1.01-1.09)], and LDL-C [OR (95% CI) = 1.05 (1.01-1.09)] were significantly associated with increased risk of CHD in T2D patients (4.8 × 10- 4 < P < 0.0197). Further adjustment for baseline lipid drug use notably attenuated the CHD association. CONCLUSIONS: The PRSs derived and validated here highlight the potential for early genomic screening and personalized risk assessment for cardiovascular disease.

Obesity, clinical, and genetic predictors for glycemic progression in Chinese patients with type 2 diabetes: A cohort study using the Hong Kong Diabetes Register and Hong Kong Diabetes Biobank.

BACKGROUND: Type 2 diabetes (T2D) is a progressive disease whereby there is often deterioration in glucose control despite escalation in treatment. There is significant heterogeneity to this progression of glycemia after onset of diabetes, yet the factors that influence glycemic progression are not well understood. Given the tremendous burden of diabetes in the Chinese population, and limited knowledge on factors that influence glycemia, we aim to identify the clinical and genetic predictors for glycemic progression in Chinese patients with T2D. METHODS AND FINDINGS: In 1995-2007, 7,091 insulin-naïve Chinese patients (mean age 56.8 ± 13.3 [SD] years; mean age of T2D onset 51.1 ± 12.7 years; 47% men; 28.4% current or ex-smokers; median duration of diabetes 4 [IQR: 1-9] years; mean HbA1c 7.4% ± 1.7%; mean body mass index [BMI] 25.3 ± 4.0 kg/m2) were followed prospectively in the Hong Kong Diabetes Register. We examined associations of BMI and other clinical and genetic factors with glycemic progression defined as requirement of continuous insulin treatment, or 2 consecutive HbA1c ≥8.5% while on ≥2 oral glucose-lowering drugs (OGLDs), with validation in another multicenter cohort of Hong Kong Diabetes Biobank. During a median follow-up period of 8.8 (IQR: 4.8-13.3) years, incidence of glycemic progression was 48.0 (95% confidence interval [CI] 46.3-49.8) per 1,000 person-years with 2,519 patients started on insulin. Among the latter, 33.2% had a lag period of 1.3 years before insulin was initiated. Risk of progression was associated with extremes of BMI and high HbA1c. On multivariate Cox analysis, early age at diagnosis, microvascular complications, high triglyceride levels, and tobacco use were additional independent predictors for glycemic progression. A polygenic risk score (PRS) including 123 known risk variants for T2D also predicted rapid progression to insulin therapy (hazard ratio [HR]: 1.07 [95% CI 1.03-1.12] per SD; P = 0.001), with validation in the replication cohort (HR: 1.24 [95% CI 1.06-1.46] per SD; P = 0.008). A PRS using 63 BMI-related variants predicted BMI (beta [SE] = 0.312 [0.057] per SD; P = 5.84 × 10-8) but not glycemic progression (HR: 1.01 [95% CI 0.96-1.05] per SD; P = 0.747). Limitations of this study include potential misdiagnosis of T2D and lack of detailed data of drug use during follow-up in the replication cohort. CONCLUSIONS: Our results show that approximately 5% of patients with T2D failed OGLDs annually in this clinic-based cohort. The independent associations of modifiable and genetic risk factors allow more precise identification of high-risk patients for early intensive control of multiple risk factors to prevent glycemic progression.

Combined Use of Common Fecal and Blood Markers for Detection of Endoscopically Active Inflammatory Bowel Disease.

INTRODUCTION: Monitoring of disease activity is essential in patients with inflammatory bowel disease. Although endoscopic remission is the ideal therapeutic goal, noninvasive biomarkers (blood and fecal) are more acceptable to patients and are less costly. We evaluated the performance of combinations of fecal and blood markers on the detection of endoscopically active disease. METHODS: Patients with ulcerative colitis (UC) or Crohn's disease (CD) on stable medications were recruited. Blood markers included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, platelet count (PLT), and hemoglobin. Fecal biomarkers included fecal calprotectin (FCT) and fecal immunochemical test (FIT). These markers were compared with the endoscopic Mayo score for UC and the Simple Endoscopic Score for CD. RESULTS: One hundred thirteen patients (mean age 44.7 years, 63.7% men, 54.9% patients with UC and 45.1% patients with CD) were recruited. FCT correlated well with FIT (r = 0.58), CRP (r = 0.56), ESR (r = 0.40), albumin (r = -0.54), PLT (r = 0.61), and hemoglobin (r = -0.35; all Ps < 0.001). Among 66 patients with endoscopic evaluation, 39.4% with endoscopically active disease had higher FCT, FIT, CRP, ESR, PLT, lower albumin, and hemoglobin compared with those in endoscopic remission (all Ps < 0.01). All 7 markers demonstrated good area under receiver operating characteristics (>0.7), with FCT being the best (0.91) for endoscopically active disease. Combining FCT and FIT improved the specificity to 95%, but the sensitivity decreased to 65.4%. In the subgroup analysis of UC, adding PLT to FIT improved the sensitivity and specificity to 100% and 90.9%, respectively. DISCUSSION: The combined use of fecal biomarkers and blood indexes is superior to the use of fecal biomarkers alone in identifying endoscopically active disease.

A Hong Kong Chinese kindred with familial hypocalciuric hypercalcaemia caused by AP2S1 mutation.

Familial hypocalciuric hypercalcaemia (FHH) is a genetic disorder of altered calcium homeostasis. Mutations in the CASR, GNA11 and AP2S1 genes have been reported to cause FHH. We report a Hong Kong Chinese kindred with FHH type 3 (FHH3) caused by mutations in AP2S1. The proband, a 51-year-old woman with hypercalcaemia, was initially diagnosed to have primary hyperparathyroidism but repeated parathyroidectomy failed to normalize her plasma calcium concentrations. Later, FHH was suspected and yet no mutations were identified in the CASR gene which causes FHH type 1 (FHH1), the most common form of FHH. Genetic testing of AP2S1 revealed a heterozygous c.43C>T (p.Arg15Cys) mutation, confirming the diagnosis of FHH3. The elder brother and niece of the proband, who both have hypercalcaemia, were found to harbour the same mutation. To our knowledge, this is the first Chinese kindred of FHH3 reported in the English literature.

Methylated Septin 9 and Carcinoembryonic Antigen for Serological Diagnosis and Monitoring of Patients with Colorectal Cancer After Surgery.

With the increasing incidence and mortality of colorectal cancer (CRC), early and accurate diagnosis is of paramount priority to combat this cancer. Epigenetic alterations such as DNA methylation are innovative biomarkers for CRC, due to their stability, frequency, and accessibility in bodily fluids. In this study, blood samples were prospectively collected from patients before and after operation for CRC for determination of methylated septin 9 (mSEPT9) and compared to carcinoembryonic antigen (CEA). The sensitivity of using mSEPT9 methylation status for diagnosing CRC was significantly higher than using elevated CEA levels (73.2% vs 48.2%; p value < 0.001). The sensitivities of both tests increased with higher tumor staging (P = 0.004 and 0.04 respectively). Combined mSEPT9 and CEA had higher accuracy than single CEA or mSEPT9 (P = 0.009 and 0.532 separately). An increase in the methylation level of mSEPT9 detected in the post-operative samples was associated with a higher mortality rate (15.2% vs 1.8%; P = 0.024) and the presence of metastasis (27.3% vs 7.0%; P = 0.013). mSEPT9 was more sensitive than CEA for diagnosing CRC, and combined mSEPT9 and CEA was more accurate. After curative resection, detection of increased mSEPT9 methylation level may indicate adverse outcomes.

Savouring and psychological well-being in family dyads coping with cancer: An actor-partner interdependence model.

Previous studies have investigated interdependence of the associations between predictors and negative psychological outcomes in dyads of cancer patients and family caregivers. This study examined the dyadic effects of perceived capability of savouring the moment on psychological well-being. A total of 152 dyads of cancer patients and caregivers reported their perceived capability of savouring the moment (Savoring Beliefs Inventory), state positive affect (Chinese Affect Scale) and life satisfaction (Satisfaction With Life Scale) within 6 months following diagnosis. Actor-Partner Interdependence Model (APIM) demonstrated that patients' and caregivers' savouring the moment was positively associated with their own positive affect and life satisfaction (actor effects: ßs = 0.309-0.603, 95% CIs = 0.171-0.502, 0.446-0.703, ps < 0.001). Patients' savouring the moment was positively associated with caregivers' positive affect (ß = 0.158, 95% CI = 0.018, 0.299, p = 0.028), whereas caregivers' savouring the moment was positively associated with patients' life satisfaction (ß = 0.158, 95% CI = 0.026, 0.289, p = 0.020). Partner effects between caregivers' savouring the moment and patients' positive affect and between patients' savouring the moment and caregivers' life satisfaction were not significant. The findings suggest the role of savouring in psychological well-being within patient-caregiver dyads, highlighting the importance of investigating positive psychological pathways in their joint adaptation.

Highly stable binder free CNTs/rGO aerogel electrode for decolouration of methylene blue & palm oil mill effluent via electro-Fenton oxidation process.

In this study, single wall carbon nanotubes (CNTs)/reduced graphene oxides (rGO) aerogels were prepared by a one-pot hydrothermal process without using a binder. The produced CNTs/rGO aerogel was used as cathode in electro-Fenton system for the decolouration of methylene blue (MB) and palm oil mill effluent (POME). The addition of CNTs increased the surface area, pore volume and conductivity of the rGO aerogel, which further enhanced their performance as cathode towards the decolouration of MB and POME via electro-Fenton reaction. Complete decolouration of MB using rGO aerogel without CNTs could not be achieved. The effect of electro-Fenton reaction parameters conducted using the aerogel samples including, current, electrolyte concentrations and pH, were investigated accordingly. The CNTs/rGO aerogel electrode also showed high stability and reusability for up to six consecutive treatment cycles for MB. Besides, the CNTs/rGO aerogel also showed good performance in treating POME with 69.8%, 47.6% and 58.1% of reduction in true colour, total organic carbon (TOC) and chemical oxygen demand (COD), respectively, via 60 minutes electro-Fenton reaction. This study showed that CNTs/rGO aerogels with high porosity and stability can be prepared using simple procedure without adding binder. This fully carbon-based aerogel can serve as effective cathode for decolouration of organic dye and effluent.