Association Between Treatment With Apixaban, Dabigatran, Rivaroxaban, or Warfarin and Risk for Osteoporotic Fractures Among Patients With Atrial Fibrillation: A Population-Based Cohort Study.

BACKGROUND: It is unclear whether anticoagulant type is associated with the risk for osteoporotic fracture, a deleterious complication of anticoagulants among patients with atrial fibrillation (AF). OBJECTIVE: To compare the risk for osteoporotic fracture between anticoagulants. DESIGN: Population-based cohort study. SETTING: Territory-wide electronic health record database of the Hong Kong Hospital Authority. PARTICIPANTS: Patients newly diagnosed with AF between 2010 and 2017 who received a new prescription for warfarin or a direct oral anticoagulant (DOAC) (apixaban, dabigatran, or rivaroxaban). Follow-up ended on 31 December 2018. MEASUREMENTS: Osteoporotic hip and vertebral fractures in anticoagulant users were compared using propensity score-weighted cumulative incidence differences (CIDs). RESULTS: There were 23 515 patients identified (3241 apixaban users, 6867 dabigatran users, 3866 rivaroxaban users, and 9541 warfarin users). Overall mean age was 74.4 years (SD, 10.8), ranging from 73.1 years (warfarin) to 77.9 years (apixaban). Over a median follow-up of 423 days, 401 fractures were identified (crude event number [weighted rate per 100 patient-years]: apixaban, 53 [0.82]; dabigatran, 95 [0.76]; rivaroxaban, 57 [0.67]; and warfarin, 196 [1.11]). After 24-month follow-up, DOAC use was associated with a lower risk for fracture than warfarin use (apixaban CID, -0.88% [95% CI, -1.66% to -0.21%]; dabigatran CID, -0.81% [CI, -1.34% to -0.23%]; and rivaroxaban CID, -1.13% [CI, -1.67% to -0.53%]). No differences were seen in all head-to-head comparisons between DOACs at 24 months (apixaban vs. dabigatran CID, -0.06% [CI, -0.69% to 0.49%]; rivaroxaban vs. dabigatran CID, -0.32% [CI, -0.84% to 0.18%]; and rivaroxaban vs. apixaban CID, -0.25% [CI, -0.86% to 0.40%]). LIMITATION: Residual confounding is possible. CONCLUSION: Among patients with AF, DOAC use may result in a lower risk for osteoporotic fracture compared with warfarin use. Fracture risk does not seem to be altered by the choice of DOAC. These findings may help inform the benefit-risk assessment when choosing between anticoagulants. PRIMARY FUNDING SOURCE: The University of Hong Kong and University College London Strategic Partnership Fund.

Galectin-3 and risk of cardiovascular events and all-cause mortality in type 2 diabetes.

AIMS: Recent clinical studies have shown that galectin-3 is a prognostic indicator in patients with coronary heart disease and in patients with heart failure. Experimental data suggest that galectin-3 may play a role in atherogenesis. We have evaluated whether serum galectin-3 level is associated with cardiovascular outcome in type 2 diabetes. MATERIALS AND METHODS: Galectin-3 was measured in baseline samples in 1495 persons with type 2 diabetes. The primary cardiovascular outcome, incident cardiovascular events, was defined as first non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or death from cardiovascular cause. The secondary outcome was all-cause mortality. RESULTS: At baseline, 12% of the subjects had prevalent cardiovascular disease. Serum galectin-3 was increased in the group with incident cardiovascular events compared with those who remained free of events during follow up (9.03 ± 2.98 ng/mL vs 8.15 ± 2.76, P < 0.01). Serum galectin-3 was also significantly increased in those subjects with a fatal outcome. The hazard ratios (HR) for cardiovascular events and all-cause mortality for individuals in the top quartile were 2.50 (95% CI 1.87, 3.36, P < 0.001) and 3.92 (95%CI 2.55, 6.01, P < 0.001), respectively. In a multivariate Cox regression analysis including traditional risk factors, log (eGFR), baseline albuminuria, and cardiovascular disease status, the HR per standard deviation change in galectin-3 was 1.13 (95% CI 1.02, 1.26, P = 0.02) for cardiovascular events and 1.17 (95% CI 1.01, 1.35, P = 0.04) for all-cause mortality. CONCLUSIONS: Serum galectin-3 is associated with adverse cardiovascular outcomes in persons with type 2 diabetes independent of traditional risk factors.

Galectin-3 is independently associated with progression of nephropathy in type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Galectin-3 has been implicated in cardiac and renal fibrosis and serves as a prognostic clinical indicator in heart failure. The aim of the present study was to evaluate whether serum galectin-3 level is associated with progressive kidney disease in type 2 diabetes. METHODS: Galectin-3 was measured in baseline samples by ELISA in 1320 participants with type 2 diabetes with eGFR ≥30 ml min-1 1.73 m-2. The primary outcome was defined as doubling of serum creatinine and/or initiation of renal replacement therapy during follow-up. The secondary outcome was progression to macroalbuminuria in individuals with normo- or microalbuminuria at baseline. RESULTS: Serum galectin-3 levels were significantly increased in a random subgroup of 270 type 2 diabetic individuals with eGFR >60 ml min-1 1.73 m-2 compared with an age- and sex-matched non-diabetic control group (7.58 ± 2.29 ng/ml vs 6.10 ± 1.91 ng/ml, respectively, p < 0.01). In the whole diabetic cohort, after a mean follow-up of 9 years, galectin-3 was independently associated with doubling of serum creatinine (HR 1.19; 95% CI 1.14, 1.24, p < 0.001) and incident macroalbuminuria (HR 1.20; 95% CI 1.12, 1.30, p < 0.001), even after adjusting for traditional risk factors, baseline eGFR and albuminuria status. Individuals with galectin-3 levels in the highest quartile had a fourfold risk of renal function loss and threefold risk of incident macroalbuminuria. CONCLUSIONS/INTERPRETATION: Serum galectin-3 was independently associated with progressive renal disease in type 2 diabetes. Further mechanistic studies are warranted to determine whether galectin-3 is simply a disease biomarker or is also a mediator of the development and progression of diabetic nephropathy.

Emergency medicine summary code for reporting CT scan results: implementation and survey results.

PURPOSE: The purpose of the study was to assess the emergency department (ED) providers' interest and satisfaction with ED CT result reporting before and after the implementation of a standardized summary code for all CT scan reporting. MATERIALS AND METHODS: A summary code was provided at the end of all CTs ordered through the ED from August to October of 2016. A retrospective review was completed on all studies performed during this period. A pre- and post-survey was given to both ED and radiology providers. RESULTS: A total of 3980 CT scans excluding CTAs were ordered with 2240 CTs dedicated to the head and neck, 1685 CTs dedicated to the torso, and 55 CTs dedicated to the extremities. Approximately 74% CT scans were contrast enhanced. Of the 3980 ED CT examination ordered, 69% had a summary code assigned to it. Fifteen percent of the coded CTs had a critical or diagnostic positive result. CONCLUSIONS: The introduction of an ED CT summary code did not show a definitive improvement in communication. However, the ED providers are in consensus that radiology reports are crucial their patients' management. There is slightly increased satisfaction with the providers with less than 5 years of experience with the ED CT codes compared to more seasoned providers. The implementation of a user-friendly summary code may allow better analysis of results, practice improvement, and quality measurements in the future.

Validity of major osteoporotic fracture diagnosis codes in the Clinical Data Analysis and Reporting System in Hong Kong.

PURPOSE: Large medical record databases facilitate epidemiology research in fracture. However, the validity of fracture in the databases is needed to ensure the reliability of data. We aimed to assess the validity of International Classification of Diseases, 9th Revision (ICD-9) code algorithms for identifying major osteoporotic fracture in the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong. METHODS: The CDARS is a database developed by the Hong Kong Hospital Authority for research purpose. We used ICD-9 code algorithm for identifying major osteoporotic fracture, including vertebral fracture, humerus fracture, forearm/wrist fracture, and hip fracture, in CDARS in 2005-2016. As high positive predictive value (PPV) is critically important in epidemiology research, we sought to determine the PPV of fracture diagnostic code in terms of ICD-9 relative to the radiography imaging and clinical notes. A total of 380 major osteoporotic fracture cases (vertebral fracture: 101 cases; humerus fracture: 81 cases; forearm/wrist fracture: 94 cases; and hip fracture: 104 cases) were randomly selected and validated. RESULTS: In 380 fracture cases, the overall PPV was 96.8%. In subgroup analysis, PPV of 100% was observed for hip, humerus, and forearm/wrist fractures, whereas PPV of 86% was observed for vertebral fracture. CONCLUSIONS: The use of ICD-9 code algorithm to identify major osteoporotic fracture in CDARS is a valid tool with a very high PPV. However, cautious interpretation is required when the study focuses on incident vertebral fracture. Copyright © 2017 John Wiley & Sons, Ltd.

Association Between Dabigatran vs Warfarin and Risk of Osteoporotic Fractures Among Patients With Nonvalvular Atrial Fibrillation.

Importance: The risk of osteoporotic fracture with dabigatran use in patients with nonvalvular atrial fibrillation (NVAF) is unknown. Objective: To investigate the risk of osteoporotic fracture with dabigatran vs warfarin in patients with NVAF. Design, Setting, and Participants: Retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with NVAF from 2010 through 2014 and prescribed dabigatran or warfarin were matched by propensity score at a 1:2 ratio with follow-up until July 31, 2016. Exposures: Dabigatran or warfarin use during the study period. Main Outcomes and Measures: Risk of osteoporotic hip fracture and vertebral fracture was compared between dabigatran and warfarin users using Poisson regression. The corresponding incidence rate ratio (IRR) and absolute risk difference (ARD) with 95% CIs were calculated. Results: Among 51 496 patients newly diagnosed with NVAF, 8152 new users of dabigatran (n = 3268) and warfarin (n = 4884) were matched by propensity score (50% women; mean [SD] age, 74 [11] years). Osteoporotic fracture developed in 104 (1.3%) patients during follow-up (32 dabigatran users [1.0%]; 72 warfarin users [1.5%]). Results of Poisson regression analysis showed that dabigatran use was associated with a significantly lower risk of osteoporotic fracture compared with warfarin (0.7 vs 1.1 per 100 person-years; ARD per 100 person-years, -0.68 [95% CI, -0.38 to -0.86]; IRR, 0.38 [95% CI, 0.22 to 0.66]). The association with lower risk was statistically significant in patients with a history of falls, fractures, or both (dabigatran vs warfarin, 1.6 vs 3.6 per 100 person-years; ARD per 100 person-years, -3.15 [95% CI, -2.40 to -3.45]; IRR, 0.12 [95% CI, 0.04 to 0.33]), but not in those without a history (0.6 vs 0.7 per 100 person-years; ARD per 100 person-years, -0.04 [95% CI, 0.67 to -0.39]; IRR, 0.95 [95% CI, 0.45 to 1.96]) (P value for interaction, <.001). Conclusions and Relevance: Among adults with NVAF receiving anticoagulation, the use of dabigatran compared with warfarin was associated with a lower risk of osteoporotic fracture. Additional study, perhaps including randomized clinical trials, may be warranted to further understand the relationship between use of dabigatran vs warfarin and risk of fracture.

Molecular Regulation and Oncogenic Functions of TSPAN8.

Tetraspanins, a superfamily of small integral membrane proteins, are characterized by four transmembrane domains and conserved protein motifs that are configured into a unique molecular topology and structure in the plasma membrane. They act as key organizers of the plasma membrane, orchestrating the formation of specialized microdomains called "tetraspanin-enriched microdomains (TEMs)" or "tetraspanin nanodomains" that are essential for mediating diverse biological processes. TSPAN8 is one of the earliest identified tetraspanin members. It is known to interact with a wide range of molecular partners in different cellular contexts and regulate diverse molecular and cellular events at the plasma membrane, including cell adhesion, migration, invasion, signal transduction, and exosome biogenesis. The functions of cell-surface TSPAN8 are governed by ER targeting, modifications at the Golgi apparatus and dynamic trafficking. Intriguingly, limited evidence shows that TSPAN8 can translocate to the nucleus to act as a transcriptional regulator. The transcription of TSPAN8 is tightly regulated and restricted to defined cell lineages, where it can serve as a molecular marker of stem/progenitor cells in certain normal tissues as well as tumors. Importantly, the oncogenic roles of TSPAN8 in tumor development and cancer metastasis have gained prominence in recent decades. Here, we comprehensively review the current knowledge on the molecular characteristics and regulatory mechanisms defining TSPAN8 functions, and discuss the potential and significance of TSPAN8 as a biomarker and therapeutic target across various epithelial cancers.

Comparison of Serum Ketone Levels and Cardiometabolic Efficacy of Dapagliflozin versus Sitagliptin among Insulin-Treated Chinese Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Insulin-treated patients with long duration of type 2 diabetes mellitus (T2DM) are at increased risk of ketoacidosis related to sodium-glucose co-transporter 2 inhibitor (SGLT2i). The extent of circulating ketone elevation in these patients remains unknown. We conducted this study to compare the serum ketone response between dapagliflozin, an SGLT2i, and sitagliptin, a dipeptidyl peptidase-4 inhibitor, among insulin-treated T2DM patients. METHODS: This was a randomized, open-label, active comparator-controlled study involving 60 insulin-treated T2DM patients. Participants were randomized 1:1 for 24-week of dapagliflozin 10 mg daily or sitagliptin 100 mg daily. Serum ß-hydroxybutyrate (BHB) levels were measured at baseline, 12 and 24 weeks after intervention. Comprehensive cardiometabolic assessments were performed with measurements of high-density lipoprotein cholesterol (HDL-C) cholesterol efflux capacity (CEC), vibration-controlled transient elastography and echocardiography. RESULTS: Among these 60 insulin-treated participants (mean age 58.8 years, diabetes duration 18.2 years, glycosylated hemoglobin 8.87%), as compared with sitagliptin, serum BHB levels increased significantly after 24 weeks of dapagliflozin (P=0.045), with a median of 27% increase from baseline. Change in serum BHB levels correlated significantly with change in free fatty acid levels. Despite similar glucose lowering, dapagliflozin led to significant improvements in body weight (P=0.006), waist circumference (P=0.028), HDL-C (P=0.041), CEC (P=0.045), controlled attenuation parameter (P=0.007), and liver stiffness (P=0.022). Average E/e', an echocardiographic index of left ventricular diastolic dysfunction, was also significantly lower at 24 weeks in participants treated with dapagliflozin (P=0.037). CONCLUSION: Among insulin-treated T2DM patients with long diabetes duration, compared to sitagliptin, dapagliflozin modestly increased ketone levels and was associated with cardiometabolic benefits.

Quality of life concerns and depression among hematopoietic stem cell transplant survivors.

PURPOSE: This study examined quality of life, transplant-related concerns, and depressive symptoms and their demographic and medical correlates at 1 to 3 years following hematopoietic stem cell transplantation (HSCT). METHODS: HSCT survivors (N=406) completed telephone-administered questionnaires that assessed demographic variables, functional status, quality of life, transplant-related concerns, and depressive symptoms. RESULTS: The most prevalent concerns among HSCT survivors included physical symptoms (e.g., fatigue and pain), maintaining current health status and employment, changes in appearance, and lack of sexual interest and satisfaction. In addition, almost one-third (32%) of survivors age 40 years and younger reported concern about their ability to have children. Unemployed survivors and those with lower incomes and worse functional status were more likely to experience poorer quality of life in multiple domains. Fifteen percent of the sample reported moderate to severe depressive symptoms, and these symptoms were higher among allogeneic transplant recipients and those with lower functional status. CONCLUSIONS: Results suggest that interventions are needed to address physical symptoms, coping with an uncertain future, infertility, and sexual issues during the early phase of HSCT survivorship.

Carbamylated Lipoproteins and Progression of Diabetic Kidney Disease.

BACKGROUND AND OBJECTIVES: Protein carbamylation is a consequence of uremia and carbamylated lipoproteins contribute to atherogenesis in CKD. Proteins can also be carbamylated by a urea-independent mechanism, and whether carbamylated lipoproteins contribute to the progression of CKD has not been investigated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A case-control study was performed to determine whether there were changes in plasma levels of carbamylated lipoproteins in individuals with type 2 diabetes with eGFR >60 ml/min per 1.73 m2 compared with a group of age- and sex-matched healthy controls. A cohort of 1320 patients with type 2 diabetes with baseline eGFR ≥30 ml/min per 1.73 m2 was longitudinally followed up to evaluate the association between carbamylated lipoproteins and progression of CKD. The primary kidney outcome was defined as doubling of serum creatinine and/or initiation of KRT during follow-up. Plasma carbamylated LDLs and HDLs was measured by ELISA. RESULTS: In individuals with diabetes with eGFR >60 ml/min per 1.73 m2, both plasma carbamylated LDL and HDL levels were higher compared with healthy controls (P<0.001). After a mean follow-up of 9 years of the diabetic cohort, individuals in the top quartile of carbamylated LDL (hazard ratio, 2.21; 95% confidence interval, 1.42 to 3.46; P<0.001) and carbamylated HDL (hazard ratio, 4.53; 95% confidence interval, 2.87 to 7.13; P<0.001) had higher risk of deterioration of kidney function compared with those in the lowest quartile. On multivariable Cox regression analysis, plasma carbamylated LDL was no longer associated with kidney outcome after adjusting for baseline eGFR and potential confounding factors. However, the association between plasma carbamylated HDL and kidney outcome remained significant and was independent of HDL cholesterol. CONCLUSIONS: Plasma carbamylated HDL but not carbamylated LDL was independently associated with progression of CKD in patients with type 2 diabetes.

Glycogenic hepatopathy as an unusual etiology of deranged liver function in a patient with type 1 diabetes: A case report.

RATIONALE: Deranged liver function is a common finding among patients with diabetes mellitus. We report a case of liver biopsy-proven glycogenic hepatopathy (GH) in a patient with long-standing poorly controlled type 1 diabetes (DM1), presented with recurrent transaminitis. PATIENT CONCERNS: A 28-year-old Chinese woman was noted to have deranged liver function with transaminases elevated to more than 15 times the upper limit of normal. DIAGNOSIS: She had underlying long-standing poorly controlled DM1. Blood tests including hepatitis serology and autoimmune panel were negative. Liver biopsy confirmed the diagnosis of GH, showing an increase in glycogen deposition with intact liver parenchymal architecture, and no inflammation or significant fibrosis. INTERVENTIONS: Her glycemic control was optimized. OUTCOMES: Her transaminase levels normalized upon subsequent follow-up with improved glycemic control. LESSONS: GH is suspected when transaminase flare occurs in patients with poorly controlled DM1, usually with exaggerated hemoglobin A1c levels, especially after drug-induced, viral, autoimmune and metabolic liver diseases are excluded. The gold standard of diagnosis is liver biopsy. When diagnosis of GH is ascertained, the mainstay of treatment is to optimize glycemic control. Typically, the transaminases may become normal within days to months after improvement of glycemic control. Compared to non-alcoholic fatty liver disease, GH is associated with favorable prognosis and runs a benign course, making this differentiation clinically important.

A zinc-finger fusion protein refines Gal4-defined neural circuits.

The analysis of behavior requires that the underlying neuronal circuits are identified and genetically isolated. In several major model species-most notably Drosophila-neurogeneticists identify and isolate neural circuits with a binary heterologous expression-control system: Gal4-UASG. One limitation of Gal4-UASG is that expression patterns are often too broad to map circuits precisely. To help refine the range of Gal4 lines, we developed an intersectional genetic AND operator. Interoperable with Gal4, the new system's key component is a fusion protein in which the DNA-binding domain of Gal4 has been replaced with a zinc finger domain with a different DNA-binding specificity. In combination with its cognate binding site (UASZ) the zinc-finger-replaced Gal4 ('Zal1') was functional as a standalone transcription factor. Zal1 transgenes also refined Gal4 expression ranges when combined with UASGZ, a hybrid upstream activation sequence. In this way, combining Gal4 and Zal1 drivers captured restricted cell sets compared with single drivers and improved genetic fidelity. This intersectional genetic AND operation presumably derives from the action of a heterodimeric transcription factor: Gal4-Zal1. Configurations of Zal1-UASZ and Zal1-Gal4-UASGZ are versatile tools for defining, refining, and manipulating targeted neural expression patterns with precision.

Association of Alendronate and Risk of Cardiovascular Events in Patients With Hip Fracture.

The risk of cardiovascular events (CVEs) with alendronate use in real-world hip fracture patients is unknown. This study aimed to investigate the risk of CVE with and without use of alendronate in patients with hip fracture. We conducted a retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with hip fracture from 2005 through 2013 were followed until November 6, 2016. Alendronate and other antiosteoporosis medications use during the study period were examined. We matched treated and nontreated patients based on time-dependent propensity score. The risks of cardiovascular mortality, myocardial infarction, and stroke between treatment groups were evaluated using conditional Cox regression stratified by match pairs. To examine the associations over time, outcomes were assessed at 1 year, 3 years, 5 years, and 10 years. Among 34,991 patients with newly diagnosed hip fracture, 4602 (13.2%) received antiosteoporosis treatment during follow-up. Physical functioning or survival prospect was not significantly different between treated and nontreated patients. A total of 4594 treated patients were matched with 13,568 nontreated patients. Results of Cox regression analysis revealed that alendronate was associated with a significantly lower risk of 1-year cardiovascular mortality (HR 0.33; 95% CI, 0.17 to 0.65) and incident myocardial infarction (HR 0.55; 95% CI, 0.34 to 0.89), whereas marginally significant reduction in risk of stroke was observed at 5 years and 10 years (HR at 5 years: 0.82; 95% CI, 0.67 to 1.00; p = 0.049; HR at 10 years: 0.83; 95% CI, 0.69 to 1.01; p = 0.065). The strength of the association declined over time but remained significant. Similar results were observed when all nitrogen-containing bisphosphonates (N-BPs) were analyzed together. These findings were robust in multiple sensitivity analyses. Additional studies in other population samples and randomized clinical trials may be warranted to further understand the relationship between use of various antiosteoporosis medication and risk of CVE in patients with hip fracture. © 2018 American Society for Bone and Mineral Research.

Validation of the Pooled Cohort equations in a long-term cohort study of Hong Kong Chinese.

BACKGROUND: The 2013 American College of Cardiology and the American Heart Association guidelines recommended the Pooled Cohort equations for evaluation of cardiovascular (CV) risk of individuals. OBJECTIVE: We investigated the usefulness of the Pooled Cohort equations in Chinese by validating this risk prediction model using the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS) cohort. METHODS: The Hong Kong CRISPS is a population-based prospective cohort study of CV risk factors among 2895 Chinese men and women (aged 25-74 years) initiated in 1995. CV events were ascertained until December 2012. The discrimination and calibration of the Pooled Cohort equations were evaluated and compared with the Framingham CV risk equation. A Hosmer-Lemeshow chi-square statistic (X(2)) of <20 indicated good calibration. RESULTS: The discrimination power of the 2 models in both men and women was moderate. The calibration score of both models were unacceptable in men (Pooled Cohort X(2), 24.1; Framingham X(2), 20.1), but was satisfactory in women (10.1 and 12.1, respectively). In men, with recalibration of the model using the CRISPS data, the accuracy of prediction improved. Recalibration, however, could not be applied to the Pooled Cohort model because the degree of miscalibration varied across the different risk categories. CONCLUSIONS: The Pooled Cohort equations provide poor calibration and moderate discrimination in Hong Kong Chinese, especially in men. In contrast, the Framingham CV risk equation can be applied to the Chinese population but requires recalibration in men.

Serum Level of Soluble Receptor for Advanced Glycation End Products Is Associated with A Disintegrin And Metalloproteinase 10 in Type 1 Diabetes.

BACKGROUND: The receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of diabetic complications, and soluble forms of the receptor (sRAGE) can counteract the detrimental action of the full-length receptor by acting as decoy. Soluble RAGE is produced by alternative splicing [endogenous secretory RAGE (esRAGE)] and/or by proteolytic cleavage of the membrane-bound receptor. We have investigated the role of A Disintegrin And Metalloproteinase 10 (ADAM10) in the ectodomain shedding of RAGE. METHODS: Constitutive and insulin-induced shedding of RAGE in THP-1 macrophages by ADAM10 was evaluated using an ADAM10-specific metalloproteinase inhibitor. Serum ADAM10 level was measured in type 1 diabetes and control subjects, and the association with serum soluble RAGE was determined. Serum total sRAGE and esRAGE were assayed by ELISA and the difference between total sRAGE and esRAGE gave an estimated measure of soluble RAGE formed by cleavage (cRAGE). RESULTS: RAGE shedding (constitutive and insulin-induced) was significantly reduced after inhibition of ADAM10 in macrophages, and insulin stimulated ADAM10 expression and activity. Diabetic subjects have higher serum total sRAGE and esRAGE (p<0.01) than controls, and serum ADAM10 was also increased (p<0.01). Serum ADAM10 correlated with serum cRAGE in type 1 diabetes (r = 0.40, p<0.01) and in controls (r = 0.31. p<0.01) but no correlations were seen with esRAGE. The association remained significant after adjusting for age, gender, BMI, smoking status and HbA1c. CONCLUSION: Our data suggested that ADAM10 contributed to the shedding of RAGE. Serum ADAM10 level was increased in type 1 diabetes and was a significant determinant of circulating cRAGE.

Acute effects of raisin consumption on glucose and insulin reponses in healthy individuals.

Raisins are popular snacks with a favourable nutrient profile, being high in dietary fibre, polyphenols and a number of vitamins and minerals, in addition to being rich in fructose. In light of evidence demonstrating improvements in glycaemic control with moderate fructose intake and low-glycaemic index (GI) fruits, our aim was to determine the GI, insulin index (II) and postprandial responses to raisins in an acute feeding setting. A total of ten healthy participants (four male and six female) consumed breakfast study meals on four occasions over a 2- to 8-week period: meal 1: white bread (WB) (108 g WB; 50 g available carbohydrate) served as the control and was consumed on two separate occasions; meal 2: raisins (R50) (69 g raisins; 50 g available carbohydrate); and meal 3: raisins (R20) (one serving, 28 g raisins; 20 g available carbohydrate). Postprandial glucose and insulin were measured over a 2 h period for the determination of GI, glycaemic load (GL) and II. The raisin meals, R50 and R20, resulted in significantly reduced postprandial glucose and insulin responses when compared with WB (P < 0·05). Furthermore, raisins were determined to be low-GI, -GL and -II foods. The favourable effect of raisins on postprandial glycaemic response, their insulin-sparing effect and low GI combined with their other metabolic benefits may indicate that raisins are a healthy choice not only for the general population but also for individuals with diabetes or insulin resistance.

Randomised trial of expressive writing for distressed metastatic breast cancer patients.

Women with metastatic breast cancer and significant psychological distress (N = 87) were assigned randomly to engage in four home-based sessions of expressive writing or neutral writing. Women in the expressive writing group wrote about their deepest thoughts and feelings regarding their cancer, whereas women in the neutral writing group wrote about their daily activities in a factual manner. No statistically significant group differences in existential and psychological well-being, fatigue and sleep quality were found at 8-weeks post-writing. However, the expressive writing group reported significantly greater use of mental health services during the study than the neutral writing group (55% vs. 26%, respectively; p < 0.05). Findings suggest that expressive writing may improve the uptake of mental health services among distressed cancer patients, but is not broadly effective as a psychotherapeutic intervention.