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BACKGROUND: Right adrenal vein (RAV) catheterization can be a very challenging step in adrenal venous sampling (AVS). Visualization of the inferior emissary vein (IEV) may be an indication of successful RAV catheterization. PURPOSE: To compare the rate of successful RAV sampling in the presence of the IEV. MATERIAL AND METHODS: Retrospective review of all consecutive patients with PA who underwent AVS between April 2009 and April 2012 was performed. A total of 30 patients were identified. Procedural images, cortisol, and aldosterone values obtained from sampling of the RAV and inferior vena cava (IVC) were reviewed. Cortisol measurements obtained from RAV samples were divided by measurements from the infra-renal IVC blood samples in order to calculate the selectivity index (SI). An SI >3 was considered indicative of technically successful RAV sampling. RESULTS: RAV sampling was considered technically successful in 29 out of 30 cases (97%). In cases of successful RAV sampling (29 patients), the IEV was identified in 25 patients (86%). The IEV was visualized in isolation in 16 patients (64%), and in conjunction with visualization of the RAV or right adrenal gland stain in nine patients (36%). The IEV was not visualized in the one case of unsuccessful RAV sampling. Visualizing the IEV had a sensitivity of 86.2% for successful RAV sampling. CONCLUSION: The IEV may serve as a reliable landmark for the RAV during RAV sampling.

Several models for the long-term development of T2DM already exist, focusing on the dynamics of the interaction between glycemia, insulinemia and β-cell mass. Current models consider representative (fasting or daily average) glycemia and insulinemia as characterizing the compensation state of the subject at some instant in slow time. This implies that only these representative levels can be followed through time and that the role of fast glycemic oscillations is neglected. An improved model (DPM15) for the long-term progression of T2DM is proposed, introducing separate peripheral and hepatic (liver and kidney) insulin actions. The DPM15 model no longer uses near-equilibrium approximation to separate fast and slow time scales, but rather describes, at each step in slow time, a complete day in the life of the virtual subject in fast time. The model can thus represent both fasting and postprandial glycemic levels and describe the effect of interventions acting on insulin-enhanced tissue glucose disposal or on insulin-inhibited hepatic glucose output, as well as on insulin secretion and β-cell replicating ability. The model can simulate long-term variations of commonly used clinical indices (HOMA-B, HOMA-IR, insulinogenic index) as well as of Oral Glucose Tolerance or Euglycemic Hyperinsulinemic Clamp test results. The model has been calibrated against observational data from the Diabetes Prevention Program study: it shows good adaptation to observations as a function of very plausible values of the parameters describing the effect of such interventions as Placebo, Intensive LifeStyle and Metformin administration. [ABSTRACT FROM AUTHOR]

Recently, we observed a 15% decrease in the incidence of type 1 diabetes (T1D) in Australian 0-4-year-old children following the introduction of RV vaccination [[2], [3]], suggesting that RV vaccination could contribute to the primary prevention of this autoimmune disease. Australian surveillance data [[11]] show that the prevalence of RV G3 strains increased slightly along with an increase in strain diversity in the post-RV vaccine era, but G3 remains a minor component of disease-causing RV strains. RV was prevalent in nurseries, and the change to rooming-in would have altered the timing of exposure to RV, delaying it until later in the first year of life when, based on NOD mouse studies [[17]-[19]], RV might promote rather than retard development of diabetes. [Extracted from the article]

Gastric emptying (GE) can be either delayed or accelerated in diabetes mellitus (DM). However, most research has focused on delayed GE mediated by a chronic hyperglycemic condition in DM. As such, the function of GE in the early stages of DM is not well understood. Interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal tract. In the present study, we investigated changes in GE and ICC networks in the early stages of DM using a streptozotocin-induced type 1 diabetic mouse model. The changes in GE were measured by the 13C-octanoic acid breath test. ICC networks were immunohistochemically detected by an antibody for c-Kit, a specific marker for ICC. Our results showed that GE in type 1 DM was significantly accelerated in the early stages of DM (2–4 weeks after onset). In addition, acute normalization of blood glucose levels by a single administration of insulin did not recover normal GE. ICC networks of the gastric antrum were significantly increased in DM and were not affected by the acute normalization of blood glucose. In conclusion, our results suggest that GE is accelerated in the early stages of DM, and it is associated with increased ICC networks. This mechanism may help to clarify a link between the onset of DM and GE disorders. [ABSTRACT FROM AUTHOR]

Purpose: To investigate if there are differences in macular capillaries between black and white subjects using optical coherence tomography angiography (OCTA) and identify potential factors underlying the epidemiologically-based higher vulnerability of black populations to diabetic retinopathy (DR). Methods: This prospective, observational cross-sectional study included 93 eyes of 47 healthy subjects with no medical history and ocular history who self-identified as black or white and were matched for age, sex, refractive error, and image quality. Subjects underwent OCTA imaging (RTVue-XR Avanti) of the superficial (SCP) and deep (DCP) capillary plexuses and choriocapillaris. AngioAnalytics was used to analyze vessel density (VD) and choriocapillaris % blood flow area (BFA) in the 1mm-diameter fovea, parafovea, and 3mm-diameter circular area including the fovea and parafovea (3x3mm image). Foveal avascular zone (FAZ) was also analyzed. Linear mixed models were used to evaluate for differences between the study groups. Results: Compared to the white subjects in this study, black subjects were found to have: lower foveal VD in the SCP (p<0.05); lower VD in the parafovea and in the 3x3mm image in the DCP (p<0.05); larger FAZ in SCP and DCP (p<0.05); and decreased choriocapillary BFA in the area underlying the fovea, parafovea, and 3x3mm image (p<0.05). Conclusion: In our study, our black subjects had decreased macular capillary vasculature compared to matched white subjects, even in early adulthood and the absence of any systemic or ocular conditions. To our knowledge, this is the first report showing that retinal and choriocapillary vascular differences may contribute to racial disparities in vulnerability to DR. [ABSTRACT FROM AUTHOR]

The profiles of polytraumatized patients in intensive care units were characterized. Serum and salivary markers were compared with normality between Classes I and II of APACHE II and between periods of hospitalization; these results were correlated. This was a prospective study on saliva charts and collection (n = 70). Profile: male, 27 years old, blunt traumas and collisions. Serum parameters with normality: decrease in pH, creatinine at admission to Class I, and at 48 and 72 hours in both classes; K+ at 48 h in Class II; Ca+ on admission in both classes and at 72 h in Class I. Increase in urea at 72 h in Class II, glucose at all times and in all classes, and Ca+ at 48 h in both classes. Class II had high Na+ at 48 and 72 h compared to Class I. In Class I, creatinine reduction occurred in 48 h and 72 h compared to admission and an increase of Ca+ at 48 h with admission. In Class II, pH and Na+ increased at 48 h and 72 h compared to admission. K+ decreased from admission to 48 h and increased from 48 h to 72 h. Urea increased from 48 to 72 hours. Creatinine decreased from admission to 48 and 72 hours. Ca+ increased from admission to 48 hours and decreased from 48 to 72 hours. There was an increase in the saliva levels in both classes and times in relation to normality. There was an increase in urea at admission, glucose at 72 h, and Ca+ at 48 h in Class II compared with Class I. Class I urea increased from admission to 48 h and Ca+ decreased from admission to 48 h. Class II urea decreased from 48 h to 72 h. Strong or very strong positive correlation was identified between blood and creatinine saliva at all times and regular and negative Ca+ at 72 h. This study provides evidence that salivary and serum biomarkers can be used together to monitor the evolution of the clinical symptoms of ICU patients. [ABSTRACT FROM AUTHOR]

Background: Diabetes is the most common comorbidity of necrotizing fasciitis (NF), but the effect of stress-induced hyperglycemia (SIH) on diabetic patients with NF has never been investigated. The aim of this study was to assess whether SIH, as determined by the glycemic gap between admission glucose levels and A1C-derived average glucose levels, predicts adverse outcomes in diabetic patients hospitalized with NF. Methods: We retrospectively reviewed the glycemic gap and clinical outcomes in 252 diabetic patients hospitalized due to NF from 2011 to 2018 in a single medical center in Taiwan. A receiver operating characteristic (ROC) curve was used to analyze the optimal cutoff values for predicting adverse outcomes. Univariate and multivariate logistic regression analyses were employed to identify significant predictors of adverse outcomes. Results: In total, 194 diabetic NF patients were enrolled. Compared with patients without adverse outcomes, patients with adverse outcomes had significantly higher glycemic gaps, Acute Physiology and Chronic Health Evaluation (APACHE) II scores and C-reactive protein (CRP) levels; lower albumin and hemoglobin levels; greater incidence of limb loss; and longer hospital and intensive care unit stays. The glycemic gap positively correlates with the laboratory risk indicator for NF scores, APACHE II scores and CRP levels. A glycemic gap of 146 mg/dL was the optimal cutoff value for predicting adverse outcomes using the ROC curve. Compared with patients with glycemic gaps ≤146 mg/dL, those with glycemic gaps >146 mg/dL had higher APACHE II scores and incidence rates of adverse outcomes, especially bacteremia and acute kidney injury. Multivariate analysis revealed that a glycemic gap >146 mg/dL and APACHE II score >15 were independent predictors of adverse outcomes, while the presence of hyperglycemia at admission was not. Conclusions: An elevated glycemic gap was significantly independently associated with adverse outcomes in diabetic NF patients. Further prospective studies are warranted to validate the role of the glycemic gap in NF patients with diabetes. [ABSTRACT FROM AUTHOR]

Objective: Although previous studies have reported a negative relationship between serum bilirubin concentration and the development of diabetes mellitus (DM), the relationship between bilirubin and insulin resistance has not been thoroughly assessed. This study was designed to determine the relationships between bilirubin, body fat distribution, and adipose tissue inflammation in patients with type 2 DM and the effect of bilirubin in an obese animal model. Method: Body fat distribution was measured using an abdominal dual bioelectrical impedance analyzer in patients with type 2 DM. We also measured glycemic control, lipid profile, serum bilirubin concentration and other clinical characteristics, and determined their relationships with body fat distribution. In the animal study, biliverdin (20 mg/kg daily) was orally administered to high-fat diet (HFD)-induced obese (DIO) mice for 2 weeks, after which intraperitoneal insulin tolerance testing was performed. Then, adipocyte area, adipocytokine expression, and macrophage polarization were evaluated in epididymal adipose tissues. Results: In the clinical study, univariate analysis showed that a lower bilirubin concentration was significantly correlated with higher body mass index, waist circumference, triglyceride, uric acid, creatinine, visceral fat area and lower HDL-C. In multivariate analyses, bilirubin concentration significantly correlated with diastolic blood pressure, creatinine, and visceral fat area. However, there was no association between bilirubin concentration and subcutaneous fat area. In the animal study, DIO mice treated with biliverdin had smaller adipocytes than untreated DIO mice and biliverdin improved HFD-induced insulin resistance. Biliverdin treatment reversed the higher gene expression of Cd11c, encoding an M1 macrophage marker, and Tnfa, encoding the proinflammatory cytokine tumor necrosis factor-α, in the adipose tissues of DIO mice. These data suggest biliverdin administration alleviates insulin resistance by ameliorating inflammation and the dysregulation of adipocytokine expression in adipose tissues of DIO mice. Conclusions: Bilirubin may protect against insulin resistance by ameliorating visceral obesity and adipose tissue inflammation. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) patients are predisposed to several diabetes-related complications. Dysregulation of the haemostatic mechanisms have been implicated. There are however no current studies assessing the levels and activity of protein C (PC), protein S (PS), and antithrombin III (AT III), which are essential in haemostatic regulation, in a single cohort of T2DM patients. This study evaluated the effect of poorly-managed T2DM on the levels and activity of PC, PS, and AT III. Methods: This cross-sectional study was conducted at the Diabetes Clinic, Cocoa Clinic in Kumasi, Ghana. A total of 242 T2DM patients, comprising 152 patients with poorly-managed diabetes and 90 well-managed diabetes patients, were recruited for the study. Fasting blood glucose, liver function tests and lipid profile were performed for each respondent. Glycated haemoglobin (HbA1c) was estimated by turbidimetric inhibition immunoassay. The levels and activity of PC, PS and AT III were measured by solid phase sandwich ELISA method. Results: There was a negative correlation between HbA1c and the levels and activity of PC, PS and AT III. The levels and activity of PC [(5.78 vs 4.64 μg/ml, p<0.0001) and (42.22 vs 36.21 U/ml, p = 0.01) respectively], PS [(22.55 vs 20.29 μg/ml, p = 0.010) and (235.94 vs 211.67 U/ml, p<0.0001) respectively] and AT III [(16.28 vs 14.41μg/ml, p<0.0001) and (176.01 vs 160.09 U/ml, p = 0.03) respectively] were significantly increased in patients with well-managed T2DM compared to the poorly-managed diabetes patients. Likewise, the levels and activity of PC, PS, and AT III was higher among T2DM patients using statins than patients who were statin-naïve. Among patients with well-managed T2DM, those who were on statins had significantly higher levels and activities of PC, PS, and AT III compared to well-managed T2DM patients not on statins. However, there no statistically significant differences between the level and activity of PC, PS, and AT III among poorly-managed T2DM patients with respect to statin status. Conclusion: Poorly-managed type 2 diabetes mellitus is associated with reduced levels and activity of PC, PS and AT III compared to well-managed T2DM. Though use of statins may improve the levels and activity of the PC, PS and AT III in T2DM, their effect is limited in the presence of poorly-controlled T2DM. Proper management of diabetes is essential to reduce the likelihood of thrombotic events among T2DM patients. [ABSTRACT FROM AUTHOR]

Background: Asians are predisposed to a lean heart failure (HF) phenotype. Data on the 'obesity paradox', reported in Western populations, are scarce in Asia and have only utilised the traditional classification of body mass index (BMI). We aimed to investigate the association between obesity (defined by BMI and abdominal measures) and HF outcomes in Asia.Methods and Findings: Utilising the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry (11 Asian regions including Taiwan, Hong Kong, China, India, Malaysia, Thailand, Singapore, Indonesia, Philippines, Japan, and Korea; 46 centres with enrolment between 1 October 2012 and 6 October 2016), we prospectively examined 5,964 patients with symptomatic HF (mean age 61.3 ± 13.3 years, 26% women, mean BMI 25.3 ± 5.3 kg/m2, 16% with HF with preserved ejection fraction [HFpEF; ejection fraction ≥ 50%]), among whom 2,051 also had waist-to-height ratio (WHtR) measurements (mean age 60.8 ± 12.9 years, 24% women, mean BMI 25.0 ± 5.2 kg/m2, 7% HFpEF). Patients were categorised by BMI quartiles or WHtR quartiles or 4 combined groups of BMI (low, <24.5 kg/m2 [lean], or high, ≥24.5 kg/m2 [obese]) and WHtR (low, <0.55 [thin], or high, ≥0.55 [fat]). Cox proportional hazards models were used to examine a 1-year composite outcome (HF hospitalisation or mortality). Across BMI quartiles, higher BMI was associated with lower risk of the composite outcome (ptrend < 0.001). Contrastingly, higher WHtR was associated with higher risk of the composite outcome. Individuals in the lean-fat group, with low BMI and high WHtR (13.9%), were more likely to be women (35.4%) and to be from low-income countries (47.7%) (predominantly in South/Southeast Asia), and had higher prevalence of diabetes (46%), worse quality of life scores (63.3 ± 24.2), and a higher rate of the composite outcome (51/232; 22%), compared to the other groups (p < 0.05 for all). Following multivariable adjustment, the lean-fat group had higher adjusted risk of the composite outcome (hazard ratio 1.93, 95% CI 1.17-3.18, p = 0.01), compared to the obese-thin group, with high BMI and low WHtR. Results were consistent across both HF subtypes (HFpEF and HF with reduced ejection fraction [HFrEF]; pinteraction = 0.355). Selection bias and residual confounding are potential limitations of such multinational observational registries.Conclusions: In this cohort of Asian patients with HF, the 'obesity paradox' is observed only when defined using BMI, with WHtR showing the opposite association with the composite outcome. Lean-fat patients, with high WHtR and low BMI, have the worst outcomes. A direct correlation between high WHtR and the composite outcome is apparent in both HFpEF and HFrEF.Trial Registration: Asian Sudden Cardiac Death in HF (ASIAN-HF) Registry ClinicalTrials.gov Identifier: NCT01633398. [ABSTRACT FROM AUTHOR]

Fragmentation of mitochondrial network has been implicated in many neurodegenerative, renal, and metabolic diseases. However, a quantitative measure of the microscopic parameters resulting in the impaired balance between fission and fusion of mitochondria and consequently the fragmented networks in a wide range of pathological conditions does not exist. Here we present a comprehensive analysis of mitochondrial networks in cells with Alzheimer’s disease (AD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), optic neuropathy (OPA), diabetes/cancer, acute kidney injury, Ca2+ overload, and Down Syndrome (DS) pathologies that indicates significant network fragmentation in all these conditions. Furthermore, we found key differences in the way the microscopic rates of fission and fusion are affected in different conditions. The observed fragmentation in cells with AD, HD, DS, kidney injury, Ca2+ overload, and diabetes/cancer pathologies results from the imbalance between the fission and fusion through lateral interactions, whereas that in OPA, PD, and ALS results from impaired balance between fission and fusion arising from longitudinal interactions of mitochondria. Such microscopic difference leads to major disparities in the fine structure and topology of the network that could have significant implications for the way fragmentation affects various cell functions in different diseases. [ABSTRACT FROM AUTHOR]

Objectives: Traits of metabolic syndrome (MetS) and biomarkers of inflammation and endothelial dysfunction were examined. We investigated the differences of various biomarkers among individuals with or without Mets in a gender-specific manner. The gender-specific associations between E-selectin and MetS were further evaluated. Methods: A total of 205 patients were recruited from the outpatient clinics of Tri-Service General Hospital, Taipei, Taiwan. Inclusion criteria were age between 20–75 years and BMI < 35 kg/m2. Demographic, anthropometric and MetS index data were compared between genders. Markers of inflammation and endothelial dysfunction were compared between individuals with or without MetS by gender. Results: Age-adjusted E-selectin values showed significant positive correlations with BMI, waist-hip ratio, fasting plasma glucose, systolic and diastolic blood pressure, triglycerides, TNF-α, hsCRP and ICAM-1, and inverse correlation with HDL cholesterol. E-selectin levels were positively correlated with numbers of MetS components in females (P < 0.001) but not in males (P = 0.125). Conclusions: Increased E-selectin levels are significantly associated with increased MetS risk in females, but not in males. [ABSTRACT FROM AUTHOR]

Asprosin is a counter-regulatory hormone to insulin which plays a role in fasting. It may therefore also play a role in hypoglycaemia unawareness, which has been subsequently examined in this pilot study. Intravenous glucose tolerance test was used to induce controlled hyperglycemia whereas a hyperinsulinemic clamp test was used to induce a controlled hypoglycaemia in 15 patients with diabetes type 1, with and without hypoglycaemia unawareness. Changes in asprosin plasma levels did not differ between patients with and without hypoglycaemia unawareness. However, nine patients with insulin resistance as well as higher liver stiffness values and low-density lipoprotein but lower high-density lipoprotein levels did not show the expected increase in asprosin plasma levels during hypoglycemia. Therefore, insulin resistance and alterations in liver structure, most likely early stages of non-alcoholic fatty liver disease, seem to be relevant in type 1 diabetes and do not only lead to elevated plasma levels of asprosin, but also to a blunted asprosin response in hypoglycemia. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate whether different levels of fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) in prediabetes are associated with hyperfiltration. Methods: A prospective cohort of 2,022 individuals aged 30–74 years took part in the PREDAPS Study. One cohort of 1,184 participants with prediabetes and another cohort of 838 participants with normal FPG and normal HbA1c were followed for 5 years. Hyperfiltration was defined as an estimated glomerular filtration rate (eGFR) above the age- and gender-specific 95th percentile for healthy control participants, while hypofiltration was defined as an eGFR below the 5th percentile. The prevalence of hyperfiltration was compared for different levels of prediabetes: level 1 of prediabetes: FPG <100 mg/dL plus HbA1c 5.7–6.0% or FPG 100–109 mg/dL plus HbA1c < 5.7%; level 2 of prediabetes: FPG <100 mg/dL plus HbA1c 6.1–6.4% or FPG 100–109 mg/dL plus HbA1c 5.7–6.0% or FPG 110–125 mg/dL plus HbA1c <5.7% and level 3 of prediabetes: FPG 100–109 mg/dL plus HbA1c 6.1–6.4% or FPG 110–125 mg/dL plus HbA1c 5.7–6.4%. Results: The participants with hyperfiltration were significantly younger, had a higher percentage of active smokers, and lower levels of hemoglobin and less use of ACEIs or ARBs. Only level 3 prediabetes based on FPG 100–109 mg/dL plus HbA1c 6.1–6.4% or FPG 110–125 mg/dL plus HbA1c 5.7–6.4% had a significantly higher odds ratio (OR) of hyperfiltration (OR 1.69 (1.05–2.74); P < 0.001) compared with no prediabetes (FPG < 100 mg/dL and HbA1c < 5.7%) after adjustment for different factors. The odds ratios for different levels of HbA1c alone in prediabetes increased progressively, but not significantly. Conclusions: Level 3 of prediabetes based on FPG 100–109 mg/dL plus HbA1c 6.1–6.4% or FPG 110–125 mg/dL plus HbA1c 5.7–6.4% had a significantly higher OR of hyperfiltration compared with participants without prediabetes. [ABSTRACT FROM AUTHOR]

We previously reported that allogeneic, intraperitoneally administered “Neo-Islets,” composed of cultured pancreatic islet cells co-aggregated with high numbers of immunoprotective and cytoprotective Adipose-derived Stem Cells, reestablished, through omental engraftment, redifferentiation and splenic and omental up-regulation of regulatory T-cells, normoglycemia in autoimmune Type-1 Diabetic Non-Obese Diabetic (NOD) mice without the use of immunosuppressive agents or encapsulation devices. Based on these observations, we are currently testing this Neo-Islet technology in an FDA guided pilot study (INAD 012–776) in insulin-dependent, spontaneously diabetic pet dogs by ultrasound-guided, intraperitoneal administration of 2x10e5 Neo-Islets/kilogram body weight to metabolically controlled (blood glucose, triglycerides, thyroid and adrenal functions) and sedated animals. We report here interim observations on the first 4 canine Neo-Islet-treated, insulin-dependent pet dogs that are now in the early to intermediate-term follow-up phase of the planned 3 year study (> 6 months post treatment). Current results from this translational study indicate that in dogs, Neo-Islets appear to engraft, redifferentiate and physiologically produce insulin, and are rejected by neither auto- nor allo-immune responses, as evidenced by (a) an absent IgG response to the allogeneic cells contained in the administered Neo-Islets, and (b) progressively improved glycemic control that achieves up to a 50% reduction in daily insulin needs paralleled by a statistically significant decrease in serum glucose concentrations. This is accomplished without the use of anti-rejection drugs or encapsulation devices. No adverse or serious adverse events related to the Neo-Islet administration have been observed to date. We conclude that this minimally invasive therapy has significant translational relevance to veterinary and clinical Type 1 diabetes mellitus by achieving complete and at this point partial glycemic control in two species, i.e., diabetic mice and dogs, respectively. [ABSTRACT FROM AUTHOR]

Early conversion to everolimus was assessed in kidney transplant recipients participating in the Eurotransplant Senior Program (ESP), a population in whom data are lacking. The SENATOR multicenter study enrolled 207 kidney transplant recipients undergoing steroid withdrawal at week 2 post-transplant (ClinicalTrials.gov [NCT00956293]). At week 7, patients were randomized (1:2 ratio) to continue the previous calcineurin inhibitor (CNI)-based regimen with mycophenolic acid (MPA) and cyclosporine or switch to a CNI-free regimen with MPA, everolimus (5–10 ng/mL) and basiliximab at weeks 7 and 12, then followed for 18 weeks to month 6 post-transplant. The primary endpoint was estimated GFR (eGFR). At week 7, 77/207 (37.2%) patients were randomized (53 everolimus, 24 control). At month 6, eGFR was comparable: 36.5±10.8ml/min with everolimus versus 42.0±13.0ml/min in the control group (p = 0.784). Discontinuation due to adverse events occurred in 27.8% of everolimus-treated patients and 0.0% of control patients (p = 0005). Efficacy profiles showed no difference. In conclusion, eGFR, safety and efficacy outcomes at month 6 post-transplant showed no difference between groups. The everolimus group experienced a higher rate of discontinuation due to adverse events. However, the high rate of non-randomization is highly relevant, indicating this to be a somewhat unstable patient population regardless of treatment. [ABSTRACT FROM AUTHOR]

Objective: To explore clinical factors associated with bacterial translocation in Japanese patients with type 2 diabetes mellitus (T2DM). Methods: The data of 118 patients with T2DM were obtained from two previous clinical studies, and were retrospectively analyzed regarding the clinical parameters associated with bacterial translocation defined as detection of bacteremia and levels of plasma lipopolysaccharide binding protein (LBP), the latter of which is thought to reflect inflammation caused by endotoxemia. Results: LBP level was not significantly different between patients with and without bacteremia. No clinical factors were significantly correlated with the detection of bacteremia. On the other hand, plasma LBP level was significantly correlated with HbA1c (r = 0.312), fasting blood glucose (r = 0.279), fasting C-peptide (r = 0.265), body mass index (r = 0.371), high-density lipoprotein cholesterol (r = -0.241), and inflammatory markers (high-sensitivity C-reactive protein, r = 0.543; and interleukin-6, r = 0.456). Multiple regression analysis identified body mass index, HbA1c, high-sensitivity C-reactive protein, and interleukin-6 as independent determinants of plasma LBP level. Conclusion: The plasma LBP level was similar in patients with and without bacteremia. While both bacteremia and LBP are theoretically associated with bacterial translocation, the detection of bacteremia was not associated with LBP level in T2DM. [ABSTRACT FROM AUTHOR]

This study aimed to assess the renopreventive effect of enalapril and/or paricalcitol on streptozotocin (STZ) diabetes-induced nephropathy and to elucidate their mechanisms of action through investigation of the effects on renal oxidative stress, antioxidant defense system and expressions of TNF-α, p53, caspase-3, and Bcl-2. Diabetes mellitus was induced in fasting male Wistar rats by single intraperitoneal injection of STZ (45 mg /kg b.w.) dissolved in citrate buffer (pH 4.5). Ten days after STZ injection, the diabetic rats were treated with enalapril (25 mg/l of drinking water) and/or paricalcitol (8 μg/kg b.w. per os) dissolved in 5% DMSO daily for 4 weeks. The obtained data revealed that the treatment of diabetic Wistar rats with enalapril and/or paricalcitol led to significant decreases in the elevated serum urea, uric acid, creatinine, sodium and potassium levels; thereby reflecting the improvement of the impaired kidney function. The deteriorated kidney lipid peroxidation, GSH content and GST and catalase activities in diabetic rats were significantly ameliorated as a result of treatment with enalapril and/or paricalcitol. The elevated fasting and post-prandial serum glucose levels and the lowered serum insulin and C-peptide levels were also improved. The treatment with enalapril and paricalcitol in combination was the most potent in decreasing the elevated serum glucose levels. Moreover, the treatment of diabetic rats successfully prevented the diabetes-induced histopathological deleterious changes of kidney and islets of Langerhans of pancreas. In association, the immunohistochemically detected pro-inflammatory cytokine, TNF-α, and apoptotic mediators, p53 and caspase-3, were remarkably decreased in kidney of diabetic rats as a result of treatment while the expression of anti-apoptotic protein Bcl-2 was increased. Based on these findings, it can be concluded that enalapril and paricalcitol alone or in combination can prevent STZ diabetes-induced nephropathy through amelioration of the glycemic state and antioxidant defense system together with the suppression of oxidative stress, inflammation and apoptosis. However, the treatment of diabetic rats with enalapril and paricalcitol in combination has no further significant improvement effects on renal function and damage when compared with enalapril or paclitaxel treated diabetic groups. [ABSTRACT FROM AUTHOR]

Purpose: To investigate intraocular pressure (IOP) readings by non-contact tonometry (NCT) and Goldmann applanation tonometry (GAT) for patients with different degrees of bilateral tearing. Methods: In this study, we reviewed the medical charts of patients complaining of different degrees of bilateral tearing. The tear meniscus height (TMH) and IOP with NCT and GAT were measured. In each patient, a comparison of IOP readings between the eye with lower TMH and the contralateral eye with higher TMH was evaluated. The TMH was graded as follows: grade 1 (low): TMH < 0.2 mm; grade 2 (moderate): 0.2 mm ≤ TMH < 0.6 mm; grade 3 (high): TMH ≥ 0.6 mm. Subsequently, a comparison of IOP readings among eyes with low, moderate, and high TMH was also performed. Results: A total of 120 eyes of 60 patients were enrolled. When comparing the two eyes of a patient, the eye with higher TMH showed higher NCT readings and larger difference in IOP readings between the two tonometries than the eye with lower TMH (P < 0.001 and P < 0.001, respectively). When TMH was classified into grades according to the degree, the high TMH eyes showed higher NCT readings than did the low and moderate TMH eyes (P < 0.001 and P = 0.001, respectively). In addition, the high TMH eyes showed a larger difference in IOP readings between the two tonometries than did the low and moderate TMH eyes (P < 0.001 and P < 0.001, respectively). Conclusion: Eyes with higher TMH showed higher NCT readings and a larger difference in IOP between the two tonometries (NCT and GAT) than those with lower TMH. In patients with tearing, the NCT value may be inaccurate, so it is necessary to measure the GAT. [ABSTRACT FROM AUTHOR]

Background: An assessment of bone strength based on bone mineral density (BMD) underestimates the risk of fracture in patients with diabetes mellitus (T2DM). However, using the trabecular bone score (TBS) for estimating bone microarchitecture, previous studies showed that bone fragility is associated with deterioration of the microstructure concomitantly with decreased BMD. This study was conducted to clarify which of these skeletal-related factors had a more prominent relationship with bone fragility. Research design and methods: A retrospective cross-sectional study was performed at Shimane University Hospital. A total of 548 Japanese patients with T2DM [257 postmenopausal women and 291 men aged over 50 years] were included. TBS of the spine was computed from dual-energy X-ray absorptiometry images obtained from BMD measurements. Results: Vertebral fractures (VFs) were identified in 74 (28.8%) women and 115 (39.5%) men. A relationship between BMD and VFs was observed in the limited subgroup of women with a BMD T-score ≤-1.0. According to multivariate logistic regression analysis, low TBS was significantly correlated with prevalent VFs, independent of BMD in both genders, except for men with a BMD T-score > -1.0. The decision tree showed that the priority factor for determining VFs was TBS, not BMD. Conclusion: Spinal microarchitecture represented by TBS was a more dominant skeletal factor for bone fragility than the decrease in bone mass, independent of BMD, in patients with T2DM. This observation suggests that loss of structural bone quality was crucial underlying pathogenesis for bone brittleness in these populations, regardless of gender. An integrated assessment of bone strength by BMD and TBS would help diagnose diabetic osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Despite dietary recommendations of polyunsaturated fatty acids (PUFAs) for cardiometabolic health, n-3 and n-6 PUFAs and their interplay in relation to diabetes risk remain debated. Importantly, data among pregnant women are scarce. We investigated individual plasma phospholipid n-3 and n-6 PUFAs in early to midpregnancy in relation to subsequent risk of gestational diabetes mellitus (GDM).Methods and Findings: Within the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (n = 2,802), individual plasma phospholipid n-3 and n-6 PUFAs levels were measured at gestational weeks (GWs) 10-14, 15-26, 23-31, and 33-39 among 107 GDM cases (ascertained on average at GW 27) and 214 non-GDM controls. Conditional logistic regression was used, adjusting for major risk factors for GDM. After adjusting for covariates, individual n-3 eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were inversely correlated with insulin-resistance markers, whereas individual n-6 dihomo-gamma-linolenic acid (DGLA) was positively correlated with insulin-resistance markers. At GW 15-26, a standard deviation (SD) increase in total n-3 PUFAs and individual n-3 DPA was associated with a 36% (adjusted odds ratio 0.64; 95% CI 0.42-0.96; P = 0.042) and 33% (0.67; 95% CI 0.45-0.99; P = 0.047) lower risk of GDM, respectively; however, the significance did not persist after post hoc false-discovery rate (FDR) correction (FDR-corrected P values > 0.05). Associations between total n-6 PUFAs and GDM were null, whereas associations with individual n-6 PUFAs were differential. Per SD increase, gamma-linolenic acid (GLA) at GWs 10-14 and DGLA at GWs 10-14 and 15-26 were significantly associated with a 1.40- to 1.95-fold higher risk of GDM, whereas docosatetraenoic acid (DTA) at GW 15-26 was associated with a 45% (0.55; 95% CI 0.37-0.83) lower risk of GDM (all FDR-corrected P values < 0.05). Null associations were observed for linoleic acid (LA) in either gestational window in relation to risk of GDM. Women with high (≥median) n-3 PUFAs and low (Conclusions: Our findings may suggest a potential role of primarily endogenously metabolized plasma phospholipid n-6 PUFAs including GLA, DGLA, and DTA in early to midpregnancy in the development of GDM. Null findings on primarily diet-derived n-3 EPA and DHA and n-6 LA do not provide strong evidence to suggest a beneficial role in prevention of GDM, although not excluding the potential benefit of EPA and DHA on glucose-insulin homeostasis given the inverse associations with insulin-resistance markers. Our findings highlight the importance of assessing individual circulating PUFAs to investigate their distinct pathophysiologic roles in glucose homeostasis in pregnancy. [ABSTRACT FROM AUTHOR]

Context: Multiple factors contribute to sexual dysfunction in men with obesity. Sex hormone levels are commonly abnormal in men with obesity and this abnormality is often the focus of management in clinical practice. The role of small fibre neuropathy in obesity-related sexual dysfunction is not well established. Objective: We aimed to investigate the relationship between sexual function, sex hormone levels and small nerve fibre morphology in men with severe obesity. Materials and methods: A prospective study of 29 men with severe obesity was undertaken. Sexual function was assessed using the European Male Ageing Study Sexual Function Questionnaire. Small nerve fibre morphology was quantified using corneal confocal microscopy. Sex hormone levels were measured by mass spectrophotometry. Results: Erectile dysfunction was present in 72% of the cohort with a higher prevalence of diabetes among the symptomatic group (88% vs 38%, p = 0.006). Corneal nerve fibre length (CNFL) and corneal nerve fibre density (CNFD) were both significantly lower in participants with erectile dysfunction compared to those without (p = 0.039 and p = 0.048 respectively). The erectile function score correlated with CNFL (r = -0.418, p = 0.034) and CNFD (r = -0.411, p = 0.037). Total testosterone and calculated free testosterone levels did not differ significantly between men with or without erectile dysfunction (median 8.8 nmol/L vs 9.0 nmol/L, p = 0.914; and median 176 pmol/L vs 179 pmol/L, p = 0.351 respectively), infrequent sexual thoughts (median 8.1 nmol/L vs 9.2 nmol/L, p = 0.650; and median 184 pmol/L, vs 176 pmol/L, p = 0.619 respectively) and decreased morning erections (median 9.0 nmol/L vs 8.8 nmol/L, p = 0.655; and median 170 pmol/L vs 193 pmol/L, p = 0.278 respectively). Conclusion: Sexual dysfunction is highly prevalent in men with severe obesity. We found an association between small fibre neuropathy with erectile dysfunction with presence of diabetes a likely a significant contributing factor. We found no associations between testosterone levels with sexual symptoms (including frequency of sexual thoughts). The influence of small nerve fibre neuropathy on response to therapeutic interventions and whether interventions that improve small fibre neuropathy can improve erectile function in this population merits further study. [ABSTRACT FROM AUTHOR]

The difficulty in obtaining as well as maintaining weight loss, together with the impairment of metabolic control in conditions like diabetes and cardiovascular disease, may represent pathological situations of inadequate neural communication between the brain and peripheral organs and tissues. Innervation of adipose tissues by peripheral nerves provides a means of communication between the master metabolic regulator in the brain (chiefly the hypothalamus), and energy-expending and energy-storing cells in the body (primarily adipocytes). Although chemical and surgical denervation studies have clearly demonstrated how crucial adipose tissue neural innervation is for maintaining proper metabolic health, we have uncovered that adipose tissue becomes neuropathic (ie: reduction in neurites) in various conditions of metabolic dysregulation. Here, utilizing both human and mouse adipose tissues, we present evidence of adipose tissue neuropathy, or loss of proper innervation, under pathophysiological conditions such as obesity, diabetes, and aging, all of which are concomitant with insult to the adipose organ as well as metabolic dysfunction. Neuropathy is indicated by loss of nerve fiber protein expression, reduction in synaptic markers, and lower neurotrophic factor expression in adipose tissue. Aging-related adipose neuropathy particularly results in loss of innervation around the tissue vasculature, which cannot be reversed by exercise. Together with indications of neuropathy in muscle and bone, these findings underscore that peripheral neuropathy is not restricted to classic tissues like the skin of distal extremities, and that loss of innervation to adipose may trigger or exacerbate metabolic diseases. In addition, we have demonstrated stimulation of adipose tissue neural plasticity with cold exposure, which may ameliorate adipose neuropathy and be a potential therapeutic option to re-innervate adipose and restore metabolic health. [ABSTRACT FROM AUTHOR]

This study aimed to examine the macrophage phenotype and its relationship to renal function and histological changes in human DN and the effect of TREM-1 on high-glucose-induced macrophage activation. We observed that in renal tissue biopsies, the expression of CD68 and M1 was apparent in the glomeruli and interstitium, while accumulation of M2 and TREM-1 was primarily observed in the interstitium. The numbers of CD68, M1, and M2 macrophages infiltrating in the DN group were increased in a process-dependent manner compared with the control group, and the intensities of the infiltrates were proportional to the rate of subsequent decline in renal function. M1 macrophages were recruited into the kidney at an early stage (I+IIa) of DN. The M1-to-M2 macrophage ratio peaked at this time, whereas M2 macrophages predominated at later time points (III) when the percentage of M1/M2 macrophages was at its lowest level. In an in vitro study, we showed that under high glucose conditions, macrophages began to up-regulate their expression of TREM-1, M1, and marker iNOS and decreased the M2 marker MR. However, the above effects of high-glucose were abolished when TREM-1 expression was inhibited by TREM-1 siRNA. In conclusion, our study demonstrated that there was a positive correlation between the M1/M2 activation state and the progress of DN, and TREM-1 played an important role in high-glucose-induced macrophage phenotype transformation. [ABSTRACT FROM AUTHOR]

Background: Anemia is a common finding in patients with diabetes, even in the absence of kidney disease and is a risk factor for adverse outcomes, including all-cause and cardiovascular mortality. Despite this, relatively little is known about the burden of anemia among adults with diabetes in sub-Saharan Africa. The aim of this study was to determine the prevalence of anemia and its association with renal disease among diabetic adult outpatients attending a hospital in Northeast Ethiopia. Methods: A cross-sectional study was conducted among 412 diabetic adults at the diabetes clinic of Dessie Referral hospital in Northeast Ethiopia, from January to April 2018. Each patient provided a blood sample for hemoglobin and serum creatinine levels and urine for albuminuria. Anemia was defined by World Health Organization criteria (<13 g/dl for men and <12 g/dl for women). Glomerular filtration rate (GFR) was estimated using the 4-variable Modification of Diet in Renal Disease (MDRD) equation. Chronic kidney disease (CKD) was classified into 5 stages based on the eGFR and albuminuria. Results: Anemia was present in 26.7% of the participants, and CKD in 43.0%. Anemia was more prevalent in patients with CKD (39.5%) than those without CKD (17.0%; P < 0.001). The prevalence of anemia increased with stage of CKD, from 22.6% at stage 1 to 100% at stage 4. Fifteen percent of the patients had anemia below the treatment threshold of 11 g ⁄dl. In multivariate analysis, older age (AOR = 2.41, 95% CI 1.11–5.21); type 2 diabetes (AOR = 2.40, 95% CI 1.14–5.08); presence of hypertension (AOR = 3.78, 95% CI 1.35–10.57); high systolic BP (AOR = 1.05, 95% CI 1.02–1.08); serum creatinine (AOR = 12.80, 95% CI 3.90–87.98) and low GFR (AOR = 9.50, 95% CI 4.05–22.28) were independently associated with greater odds for the presence of anemia Conclusions: Anemia is commonly present among diabetic adults attending our diabetes outpatient clinic in Northeast Ethiopia, including those without kidney disease. Our findings highlight the need for incorporating anemia screening into routine diabetes care to enable early detection and treatment of anemia and hence improve the overall care of patients with diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Heart rate recovery (HRR) is a marker of parasympathetic activity recovery after exercise, and it is associated with cardiovascular mortality and total mortality. Impaired renal function is also associated with cardiac mortality. The aim of this study was to investigate the association between HRR after exercise and renal function in patients referred for a treadmill exercise test. Patients and methods: This cross-sectional study was conducted at a regional hospital in southern Taiwan. Patients who completed a symptom-limited treadmill exercise test from January 2015 to February 2018 were recruited. Before the treadmill exercise test, patients were asked to complete a questionnaire on the past disease history and lifestyle factors. Serum creatinine measurement within two years prior to or after the date of the treadmill exercise test of the patients was also obtained from the medical records for these patients. Estimated glomerular filtration rate (eGFR) was calculated. Simple and multiple linear regression analyses were performed to investigate the association between one-minute HRR and eGFR. Results: A total of 2,825 patients completed the treadmill exercise test, and serum creatinine measurement was identified from medical records for 2,153 patients (76.2%). Multiple linear regression analysis revealed that a lower eGFR was significantly associated with lower one-minute HRR (P< 0.001), adjusting for other significant independent factors, including age, waist circumference, type 2 diabetes mellitus, and smoking. Conclusions: In this cross-sectional observational study, a lower eGFR was significantly and independently associated with decreased one-minute HRR, suggesting that parasympathetic activity recovery after exercise could be impaired by a decrease in renal function. [ABSTRACT FROM AUTHOR]

Background: Sleep duration affects health in various ways. The objective of the present study was to investigate the relationships among sleep duration, daytime napping and kidney function in a middle-aged apparently healthy Chinese population. Methods: According to self-reported total sleep and daytime napping durations, 33,850 participants who were 38–90 years old and recruited from eight regional centers were divided into subgroups. Height, weight, waist circumference, hip circumference, blood pressure, biochemical indexes, fasting blood glucose (FBG), postprandial blood glucose (PBG), HbA1c, creatinine and urinary albumin-creatinine ratio (UACR) were measured and recorded for each subject. Microalbuminuria was defined as UACR ≥30 mg/g, chronic kidney disease (CKD) was defined as eGFR <60 ml/min, and hyperfiltration was defined as eGFR ≥135 ml/min. Multiple logistic regression was applied to investigate the association between sleep and kidney function. Results: Compared to sleeping for 7–8 h/day, the ORs for microalbuminuria for sleeping for >9 h/day, 8–9 h/day 6–7 h/day and <6 h/day were 1.343 (1.228–1.470, P<0.001), 1.223 (1.134–1.320, P<0.001), 1.130 (1.003–1.273, P = 0.045) and 1.140 (0.908–1.431, P = 0.259), respectively. The eGFR levels exhibited a U-shaped association with sleep duration among subjects with an eGFR ≥90 ml/min and an N-shaped association with sleep duration among subjects with an eGFR <90 ml/min. The OR for hyperfiltration for >9 h/day of sleep was 1.400 (1.123–1.745, P = 0.003) among participants with an eGFR ≥90 ml/min. Daytime napping had a negative effect on renal health. Compared to the absence of a napping habit, the ORs for microalbuminuria for 0–1 h/day, 1–1.5 h/day and >1.5 h/day of daytime napping were 1.552 (1.444–1.668, P<0.001), 1.301 (1.135–1.491, P<0.001) and 1.567 (1.353–1.814, P<0.001), respectively. Conclusion: The association of total sleep duration with renal health outcomes is U-shaped. Daytime napping has a negative effect on renal health. [ABSTRACT FROM AUTHOR]

Introduction: Telomeres and telomerase play important role in maintaining chromosome integrity and genomic stability. Recent epidemiologic data showed inconsistent findings which suggested that both short and long leukocyte telomeres could be associated with increased risk of pancreatic cancer. We prospectively examined the association between telomere length and pancreatic cancer risk in a population-based cohort study. Methods: The Singapore Chinese Health Study recruited 63,257 Chinese aged 45 to 74 years from 1993 to 1998 in Singapore. Relative telomere length in peripheral blood leukocytes was quantified using a validated monochrome multiplex quantitative polymerase chain reaction method in 26,540 participants, including 116 participants who later developed pancreatic cancer after an average of 13 years of follow-up. Cox proportional hazard regression method was used to calculate hazard ratio (HR) and its 95% confidence interval (CI) of pancreatic cancer risk associated with telomere length, with adjustment for confounding factors. Results: Longer telomeres were significantly associated with higher risk of pancreatic cancer (Ptrend = 0.02). Compared with lowest quartile, subjects with highest quartile of telomere length had an HR of 2.18 (95% CI: 1.25–3.80) for developing pancreatic cancer. In stratified analysis, this association remained among pancreatic adenocarcinoma patients but not among pancreatic non-adenocarcinoma patients. In continuous scale, the HRs and 95% CIs were 3.08 (1.17–8.11) for adenocarcinoma patients and 1.47 (0.43–5.06) for non-adenocarcinoma patients. The HRs and 95% CIs of the highest quartile of telomere length, compared with the lowest quartile, for adenocarcinoma and non-adenocarcinoma were 2.50 (1.22–5.13) and 1.63 (0.66–4.03), respectively. The length of follow-up from the collection of blood for the measurement of telomere length to the diagnosis of cancer (median = 8.0, range: from 5.0 months to 16.2 years) had no significant impact on the association between telomere length and pancreatic cancer risk. Conclusions: The present study demonstrates that longer telomeres are associated with increased risk of overall pancreatic cancer. [ABSTRACT FROM AUTHOR]

Diabetes plays an important role in the complex relationship between chronic kidney disease (CKD) and cardiovascular disease. This retrospective observational study compared the influence of estimated glomerular filtration rate (eGFR) and proteinuria on the risk of major adverse cardiovascular event (MACE; myocardial infarction or stroke) in CKD patients with and without diabetes. Data were from a linked database of UK electronic health records. Individuals with CKD and no prior MACE were classified as type 1 diabetes (T1DM; n = 164), type 2 diabetes (T2DM; n = 9,711), and non-diabetes (non-DM; n = 75,789). Monthly updated time-dependent Cox proportional hazard models were constructed to calculate adjusted hazard ratios (aHRs) for progression to MACE from first record of abnormal eGFR or proteinuria (index date). In non-DM, aHRs (95% CIs) by baseline eGFR category (referent G2) were G1: 0.70 (0.55–0.90), G3a: 1.28 (1.20–1.35), G3b: 1.64 (1.52–1.76), G4: 2.19 (1.98–2.43), and G5: 3.12 (2.44–3.99), and by proteinuria category (referent A1) were A2: 1.13 (1.00–1.28), A2/3 (severity indeterminable): 1.58 (1.28–1.95), and A3: 1.64 (1.38–1.95). In T2DM, aHRs were G1: 0.98 (0.72–1.32), G3a: 1.18 (1.03–1.34), G3b: 1.31 (1.12–1.54), G4: 1.87 (1.53–2.29), G5: 2.87 (1.82–4.52), A2: 1.22 (1.04–1.42), A2/3: 1.45 (1.17–1.79), and A3: 1.82 (1.53–2.16). Low numbers in T1DM precluded analysis. Modelling T2DM and non-DM together, aHRs were, respectively, G1: 3.23 (2.38–4.40) and 0.70 (0.55–0.89); G2: 3.18 (2.73–3.70) and 1.00 (referent); G3a: 3.65 (3.13–4.25) and 1.28 (1.21–1.36); G3b: 4.01 (3.40–4.74) and 1.65 (1.54–1.77); G4: 5.78 (4.70–7.10) and 2.21 (2.00–2.45); G5: 9.00 (5.71–14.18) and 3.14 (2.46–4.00). In conclusion, reduced eGFR and proteinuria were independently associated with increased risk of MACE regardless of diabetes status. However, the risk of MACE in the same eGFR state was 4.6–2.4 times higher in T2DM than in non-DM. [ABSTRACT FROM AUTHOR]

Background: Diabetic cardiomyopathy (DM CMP) is defined as cardiomyocyte damage and ventricular dysfunction directly associated with diabetes independent of concomitant coronary artery disease or hypertension. Matrix metalloproteinases (MMPs), especially MMP-2, have been reported to underlie the pathogenesis of DM CMP by increasing extracellular collagen content. Purpose: We hypothesized that two discrete MMP-2 isoforms (full length MMP-2, FL-MMP-2; N-terminal truncated MMP-2, NTT-MMP-2) are induced by high glucose stimulation in vitro and in an experimental diabetic heart model. Methods: Rat cardiomyoblasts (H9C2 cells) were examined to determine whether high glucose can induce the expression of the two isoforms of MMP-2. For the in vivo study, we used the streptozotocin-induced DM mouse heart model and age-matched controls. The changes of each MMP-2 isoform expression in the diabetic mice hearts were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical stains were conducted to identify the location and patterns of MMP-2 isoform expression. Echocardiography was performed to compare and analyze the changes in cardiac function induced by diabetes. Results: Quantitative RT-PCR and immunofluorescence staining showed that the two MMP-2 isoforms were strongly induced by high glucose stimulation in H9C2 cells. Although no definite histologic features of diabetic cardiomyopathy were observed in diabetic mice hearts, left ventricular systolic dysfunction was determined by echocardiography. Quantitative RT-PCR and IHC staining showed this abnormal cardiac function was accompanied with the increases in the mRNA levels of the two isoforms of MMP-2 and related to intracellular localization. Conclusion: Two isoforms of MMP-2 were induced by high glucose stimulation in vitro and in a Type 1 DM mouse heart model. Further study is required to examine the role of these isoforms in DM CMP. [ABSTRACT FROM AUTHOR]

Background and objectives: In the present article, we explore a novel strategy of selenium nanoparticles (Se-NPs) for the treatment of type 2 diabetes mellitus (T2DM) by investigating the effect of Se-NPs alone and in combination with standard anti-diabetic drug metformin (MET) in high-fat diet/streptozotocin (HFD/STZ)-induced T2DM. Methods: HFD was supplemented daily to experimental rats for 8 weeks, followed by a single low dose injection of 35 mg/kg of STZ to induce T2DM. The synergistic effect of the different therapeutic strategies on diabetic complications was evaluated after the Se-NPs and MET administration for 8 weeks. Molecular and biochemical analyses were conducted to figure out the effectiveness of our treatment on insulin sensitivity, oxidative mediators and inflammatory markers. Results: Our observations demonstrated that HFD/STZ-induced rats have a toxic effect on serum and hepatic tissues resulted in inducing remarkable oxidative damage and hyper-inflammation with a significant disturbance in the insulin signaling pathway. Experimental animals either treated with mono-therapeutic-two doses Se-NPs (0.1 and 0.4 mg/kg) and/or MET (100 mg/kg) alone as well as the combined therapy resulted in a remarkable protective anti-diabetic effect illustrated by significant decreases in fasting blood glucose and insulin levels after 8 weeks treatment. At the same time, the levels of active insulin signaling proteins pIRS1/pAKT/pGSK-3β/pAMPK were significantly improved. Moreover, Se-NPs exhibited an anti-inflammatory effect by the mitigation of cytokine expression and a balance between oxidative stress and antioxidant status was restored. Furthermore, the anti-diabetic drug MET administration also exhibited a significant improvement in diabetic complications after the treatment period. Conclusion: This study provides mightily the mechanism of action of combined Se-NPs and MET as a promising therapeutic alternative that synergistically alleviates most of diabetic complications and insulin resistance. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) is a major sexual problem for men. Nogo-B receptor (NgBR) has been found to be involved in the regulation of vascular remodeling and angiogenesis. The present study explores the effects of NgBR in penile corpus cavernosum in rats with diabetic ED. Firstly, the ED model of Sprague Dawley rats was established. Hematoxylin-eosin staining and Masson staining were conducted to observe pathological morphology. Immunochemical assay was adopted to detect α-smooth muscle actin (α-SMA), NgBR and intercellular cell adhesion molecule-1 (ICAM-1) expression. Reverse transcription quantitative polymerase chain reaction assay and Western blot analysis were carried out for the assessment of NgBR, factors correlated to ICAM-1, including steroid receptor coactivator (SRC) and proline-rich tyrosine kinase2 (PYK2), and factors associated with apoptosis, including B-cell lymphoma-2 (Bcl-2), Bcl-2 associated protein X (Bax), caspase 3 and cleaved-caspase 3. The results found that capillaries and vascular smooth muscle cell content reduced, and NgBR and ICAM-1 were elevated in rats with diabetic ED. si-NgBR relieved ED by decreasing penile corpus cavernosum smooth muscle systolic percentage and increasing erectile time and rate, intracavernous pressure (ICP)/mean arterial pressure (MAP) and diastolic percentage, improving the pathological changes and inhibiting cavernosum cell apoptosis. si-NgBR also resulted in the down-regulation of ICAM-1 and downstream SRC and PYK2 and promoted α-SMA expression. In conclusion, si-NgBR can provide a potential therapy for diabetic ED in rats by down-regulating ICAM-1, SRC and PYK2, making it a potential therapeutic option for diabetic ED. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is third in prevalence and mortality among all cancers in the US. Currently, the United States Preventative Services Task Force (USPSTF) recommends anyone ages 50–75 and/or with a family history to be screened for CRC. To improve screening specificity and sensitivity, we have built an artificial neural network (ANN) trained on 12 to 14 categories of personal health data from the National Health Interview Survey (NHIS). Years 1997–2016 of the NHIS contain 583,770 respondents who had never received a diagnosis of any cancer and 1409 who had received a diagnosis of CRC within 4 years of taking the survey. The trained ANN has sensitivity of 0.57 ± 0.03, specificity of 0.89 ± 0.02, positive predictive value of 0.0075 ± 0.0003, negative predictive value of 0.999 ± 0.001, and concordance of 0.80 ± 0.05 per the guidelines of Transparent Reporting of Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) level 2a, comparable to current risk-scoring methods. To demonstrate clinical applicability, both USPSTF guidelines and the trained ANN are used to stratify respondents to the 2017 NHIS into low-, medium- and high-risk categories (TRIPOD levels 4 and 2b, respectively). The number of CRC respondents misclassified as low risk is decreased from 35% by screening guidelines to 5% by ANN (in 60 cases). The number of non-CRC respondents misclassified as high risk is decreased from 53% by screening guidelines to 6% by ANN (in 25,457 cases). Our results demonstrate a robustly-tested method of stratifying CRC risk that is non-invasive, cost-effective, and easy to implement publicly. [ABSTRACT FROM AUTHOR]

Objective: Detection of vascular endothelial growth factor (VEGF) levels in ocular tissue may perhaps provide insight into the role of VEGF in the pathogenesis and progression of diabetic retinopathy (DR). The aim of this study was to evaluate the levels of VEGF in tears and serum amongst type 2 diabetes mellitus (DM) patients. Methods: A comparative cross-sectional study was conducted between August 2016 and May 2018 involving type 2 DM patients with no DR, non-proliferative DR (NPDR), and proliferative DR (PDR). Tear samples were collected using no.41 Whatman filter paper (Schirmer strips) and 5 mL blood samples were drawn by venous puncture. VEGF levels in tears and serum were measured by enzyme-linked immunosorbent assay. Results: A total of 88 type 2 DM patients (no DR: 30 patients, NPDR: 28 patients, PDR: 30 patients) were included in the study. Mean tear VEGF levels were significantly higher in the NPDR and PDR groups (114.4 SD 52.5 pg/mL and 150.8 SD 49.7 pg/mL, respectively) compared to the no DR group (40.4 SD 26.5 pg/mL, p < 0.001). There was no significant difference in the mean serum VEGF levels between the three groups. There was a fair correlation between serum and tear VEGF levels (p = 0.015, r = 0.263). Conclusion: VEGF levels in tears were significantly higher amongst diabetic patients with DR compared to those without DR and were significantly associated with the severity of DR. There was a fair correlation between serum and tear VEGF levels. Detection of VEGF in tears is a good non-invasive predictor test for the severity of DR. A large cohort study is needed for further evaluation. [ABSTRACT FROM AUTHOR]

Purpose: To examine outcomes of 23-gauge (23G) pars plana vitrectomy (PPV) for complex diabetic tractional retinal detachment (TRD) in Chicago's Cook County Health and Hospitals System (CCHHS). Materials and methods: This is a retrospective noncomparative study of diabetic TRD cases that underwent PPV at CCHHS. Primary retinal reattachment rate, visual function, and postoperative complications were analyzed. Results: Sixty nine consecutive cases were included. Primary reattachment and final attachment were achieved in 68/69 eyes (98.6%). Secondary retinal detachment was noted in 1 eye (1.4%). Vitreous hemorrhage requiring repeat PPV developed in 5 eyes (7.2%) and reoperation due to other complications was required in 4/69 eyes (5.8%). Perfluoropropane (C3F8) gas tamponade was used in 91.3% of eyes and silicone oil in 8.7% of eyes. Mean LogMAR visual acuity significantly improved from 1.84 ± 0.61 to 0.93 ± 0.66, (P<0.0001). Vision was stabilized or improved in 66 eyes (95.7%). Visual acuity of 20/200 or better was achieved in 49/69 eyes (71.0%) and 20/50 or better in 16/69 eyes (23.2%). Conclusions: Even in patients with severe and advanced diabetic TRD pathology and unique demographics as seen in CCHHS, modern vitrectomy techniques can provide excellent anatomical and visual outcomes. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the action of molecules in carbohydrate metabolism disorders during pregnancy. The concentration of different types of cytokines and vascular endothelial growth factor (VEGF) in the plasma were measured in 4 groups of women: Group I, normal pregnancy (n = 10); Group II, patients with gestational DM (n = 12); Group III, pregnant patients with preexisting DM (n = 16); and Group IV, diabetic non-pregnant women (n = 22). The plasma VEGF concentration was significantly higher in the women in Group IV than in other groups (P <0.01). The concentration of the soluble form of the VEGF receptor-1 (sVEGFR-1) was significantly higher in Group I than in other groups (P <0.01). The concentration of soluble form of the VEGF receptor-2 (sVEGFR-2) was significantly lower in Groups I than in other groups (P <0.05). The concentrations of monocyte chemotactic protein-1 (MCP-1) and eotaxin were significantly lower in Group I than in Groups III and IV. The levels of interleukin (IL)-8, IL-6, and tumor necrosis factor-α (TNF-α) were significantly higher in Group I than in Group IV. Both the VEGF-related molecules and the Inflammatory cytokines are altered in pregnant women with the carbohydrate metabolism disorders. [ABSTRACT FROM AUTHOR]

Background: Based on the association of common GLIS3 variants with various forms of diabetes and the biological role of GLIS3 in beta-cells, we sequenced GLIS3 in non-diabetic and diabetic Danes to investigate the effect of rare missense variants on glucose metabolism. Methods: We sequenced 53 patients with maturity-onset diabetes of the young (MODY), 5,726 non-diabetic participants, 2,930 patients with newly diagnosed type 2 diabetes and 206 patients with glutamic acid decarboxylase antibody (GADA) -positive diabetes. Results: In total we identified 86 rare (minor allele frequency < 0.1%) missense variants. None was considered causal for the presence of MODY. Among patients with type 2 diabetes, we observed a higher prevalence of rare GLIS3 missense variants (2.5%) compared to non-diabetic individuals (1.8%) (odds ratio of 1.37 (interquartile range:1.01–1.88, p = 0.04)). A significantly increased HbA1c was found among patients with type 2 diabetes and with GADA-positive diabetes carrying rare GLIS3 variants compared to non-carriers of rare GLIS3 variants with diabetes (p = 0.02 and p = 0.004, respectively). One variant (p.I28V) was found to have a minor allele frequency of only 0.03% among patients with type 2 diabetes compared to 0.2% among non-diabetic individuals suggesting a protective function (odds ratio of 0.20 (interquartile range: 0.005–1.4, p = 0.1)), an effect which was supported by publically available data. This variant was also associated with a lower level of fasting plasma glucose among non-diabetic individuals (p = 0.046). Conclusion: Rare missense variants in GLIS3 associates nominally with increased level of HbA1c and increased risk of developing type 2 diabetes. In contrast, the rare p.I28V variant associate with reduced level of fasting plasma glucose and may be protective against type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Sleep-disordered breathing (SDB) is common in patients with kidney disease; but often underdiagnosed as it is infrequently assessed in clinical practice. The objective of this study was to assess the risk factors of SDB in haemodialysis patients, and to identify useful assessment tools to detect SDB in this population. Methods: We used nocturnal oximetry, Epworth Sleepiness Scale (ESS) and STOPBANG questionnaire to screen for SDB in haemodialysis patients. Presence of SDB was defined by Oxygen desaturation index (ODI≥5/h), and further confirmed by apnoea-hypopnea index (AHI) from an in-laboratory polysomnography. Blood samples were collected prior to commencing a haemodialysis treatment. Results: SDB was detected in 70% of participants (N = 107, mean age 67 years). STOPBANG revealed that 89% of participants were at risk of SDB; however, only 17% reported daytime sleepiness on the ESS. Of the participants who underwent polysomnography (n = 36), obstructive sleep apnoea was identified in 86%, and median AHI was 34.5/h. Oximetry and AHI results were positively correlated (r = 0.62, P = 0.0001), as were oximetry and STOPBANG (r = 0.48; P<0.0001), but not ESS (r = 0.19; P = 0.08). Multivariate analysis showed that neck circumference (OR: 1.20; 95% CI: 1.07–1.34; P = 0.02) and haemoglobin (OR: 0.93; 95% CI: 0.88–0.97; P = 0.003) were independently associated with the presence of SDB. Conclusion: Dialysis patients with a large neck circumference and anaemia are at risk of SDB; using nocturnal oximetry is practical and reliable to screen for SDB and should be considered in routine management of dialysis patients, particularly for those who demonstrate risk factors. [ABSTRACT FROM AUTHOR]

Objective: To compare systemic conditions at the time of diagnosis between patients with central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). Design: This study included patients diagnosed with CRVO or BRVO between February 2009 and August 2017 at three branch hospitals of Hallym University Medical Center. Demographic and anthropometric variables, systemic comorbidity profiles, and laboratory findings at diagnosis were collected from a clinical data warehouse system, and were compared between the CRVO and BRVO groups. Result: Four hundred and seventeen patients with CRVO and 1,511 patients with BRVO were included. The mean age was 61.8 ± 13.9 years, which was comparable between two groups (P = .332). Female proportion was higher in the BRVO group (55.0%) than in the CRVO group (48.0%; P = .013). Diabetes mellitus (P = .017) and chronic kidney disease (P = .004) were more prevalent in the CRVO group. Serum homocysteine level was abnormally high in 23.5% of CRVO patients and in 8.4% of BRVO patients (P < .001). Blood urea nitrogen and serum creatinine levels were abnormally elevated in more subjects with CRVO (P = .002). Conclusion: CRVO is associated with higher prevalence of diabetes mellitus and chronic kidney disease, as well as with elevated serum homocysteine level. These results might suggest a difference between the pathophysiologies of CRVO and BRVO. [ABSTRACT FROM AUTHOR]

Background: Although hypokalemia has been viewed as a significant concern among patients with heart failure (HF), recent advances in HF management tend to increase the risk of hyperkalemia. Objective: To characterize contemporary data regarding correlates and prognostic values of dyskalemia in patients with HF. Design, setting, and participants: In cross-sectional and longitudinal analyses, we studied 142,087 patients with newly diagnosed HF in US nationwide Veterans Administration database from 2005 through 2013. Exposures: Demographic characteristics, laboratory variables, comorbidities, and medication use for the analysis of correlates of dyskalemia as well as potassium level in the analysis of mortality. Main Outcomes and Measures: Dyskalemia and mortality. Results: Hypokalemia (<3.5 mmol/L) at baseline was observed in 3.0% of the population, whereas hyperkalemia (≥5.5 mmol/L) was seen in 0.9%. An additional 20.4% and 5.7% had mild hypokalemia (3.5–3.9 mmol/L) and mild hyperkalemia (5.0–5.4 mmol/L). Key correlates were black race, higher blood pressure, and use of potassium-wasting diuretics for hypokalemia, and lower kidney function for hyperkalemia. Baseline potassium levels showed a U-shaped association with mortality, with the lowest risk between 4.0–4.5 mmol/L. With respect to potassium levels over a year after HF diagnosis, persistent (>50% of measurements), intermittent (>1 occurrence but ≤50%), and transient (1 occurrence) hypo- and hyperkalemia were also related to increased mortality in a graded fashion regardless of the aforementioned thresholds for dyskalemia. These dyskalemic patterns were also related to other clinical actions and demands such as emergency room visit. Conclusions: Potassium levels below 4 mmol/L and above 5 mmol/L at and after HF diagnosis were associated with poor prognosis and the clinical actions. HF patients (particularly with risk factors for dyskalemia like black race and kidney dysfunction) may require special attention for both hypo- and hyperkalemia. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is featured by increased plasma very low density lipoproteins (VLDL). The extent to which plasma apolipoprotein E (ApoE) levels are elevated in NAFLD is unclear. We determined whether plasma ApoE is elevated in subjects with suspected NAFLD. Plasma ApoE and genotypes were determined in 6,762 participants of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort. A Fatty Liver Index (FLI) ≥ 60 was used as a proxy of NAFLD. A total of 1,834 participants had a FLI ≥ 60, which coincided with increased triglycerides, non-HDL cholesterol, ApoB and ApoE (all P<0.001). In multivariable linear regression analysis, plasma ApoE levels were positively associated with an elevated FLI when taking account of ApoE genotypes and other clinical and laboratory covariates (fully adjusted model: β = 0.201, P<0.001). Stratified analysis for ApoE genotypes (ApoE ε3ε3 homozygotes, ApoE ε2 carriers, and ApoE ε3ε4 and ε4ε4 carriers combined), also showed positive associations of plasma ApoE levels with an elevated FLI in each group (all P<0.001). In conclusion, it is suggested that NAFLD is characterized by increased plasma ApoE levels, even when taking account of the various ApoE genotypes. Increased plasma ApoE may contribute to altered VLDL metabolism and to increased atherosclerosis susceptibility in NAFLD. [ABSTRACT FROM AUTHOR]

We aimed to investigate the clinical factors affecting the therapeutic effectiveness of the sodium–glucose cotransporter-2 inhibitor empagliflozin in patients with type 2 diabetes mellitus (T2DM). We reviewed the medical records of 374 T2DM patients aged between 20 and 75 years who were prescribed empagliflozin 10 mg or 25 mg as add-on therapy for more than 90 consecutive days. Changes in hemoglobin A1c (HbA1c) from baseline levels and the reduction in body weights of the study participants were assessed. We found that younger patients (≤ 50 years), patients with the highest levels of HbA1c (>9%) at baseline, patients with an estimated glomerular filtration rate (eGFR) of >90 mL/min/1.73 m2, and patients with a shorter duration of T2DM (< 10 years) were more likely to exhibit a better glycemic response. Multivariate linear regression analysis revealed that a shorter duration of T2DM, higher baseline levels of HbA1c, and higher eGFR were positively associated with HbA1c reduction. Higher BMI and lower HbA1c levels were predictors of a more significant reduction in body weight among patients taking empagliflozin. The glucose-lowering effect of empagliflozin was more evident in T2DM patients with higher baseline HbA1c levels, better renal function, and shorter duration of T2DM. [ABSTRACT FROM AUTHOR]

Dyslipidemia is a well-established risk factor for cardiovascular diseases. Although, advances in genome-wide technologies have enabled the discovery of hundreds of genes associated with blood lipid phenotypes, most of the heritability remains unexplained. Here we performed targeted resequencing of 13 bona fide candidate genes of dyslipidemia to identify the underlying biological functions. We sequenced 940 Sikh subjects with extreme serum levels of hypertriglyceridemia (HTG) and 2,355 subjects were used for replication studies; all 3,295 participants were part of the Asian Indians Diabetic Heart Study. Gene-centric analysis revealed burden of variants for increasing HTG risk in GCKR (p = 2.1x10-5), LPL (p = 1.6x10-3) and MLXIPL (p = 1.6x10-2) genes. Of these, three missense and damaging variants within GCKR were further examined for functional consequences in vivo using a transgenic zebrafish model. All three mutations were South Asian population-specific and were largely absent in other multiethnic populations of Exome Aggregation Consortium. We built different transgenic models of human GCKR with and without mutations and analyzed the effects of dietary changes in vivo. Despite the short-term of feeding, profound phenotypic changes were apparent in hepatocyte histology and fat deposition associated with increased expression of GCKR in response to a high fat diet (HFD). Liver histology of the GCKRmut showed severe fatty metamorphosis which correlated with ~7 fold increase in the mRNA expression in the GCKRmut fish even in the absence of a high fat diet. These findings suggest that functionally disruptive GCKR variants not only increase the risk of HTG but may enhance ectopic lipid/fat storage defects in absence of obesity and HFD. To our knowledge, this is the first transgenic zebrafish model of a putative human disease gene built to accurately assess the influence of genetic changes and their phenotypic consequences in vivo. [ABSTRACT FROM AUTHOR]

Background/Aim: No-reflow is a serious and frequent event during primary percutaneous coronary intervention (PPCI) for acute ST segment elevation myocardial infarction (STEMI). The aim of this study was to identify possible predictors for no-reflow. Patients and methods: We investigated 218 patients with acute anterior STEMI who underwent PPCI from December 2016 to December 2018. No-reflow was defined as a coronary TIMI flow grade of ≤ 2. TIMI flow grade 3 was defined as normal reflow. Results: In our study, the no-reflow phenomenon was observed in 39 patients (18%) during angiography. The patients of no-reflow group were found to be more older, diabetics, longer pain-to-balloon time, lower blood pressure, higher platelet counts and higher levels of D-Dimer and Cystatin C (Cys-C). In multivariate logistic regression analysis, only diabetes (OR = 0.371, 95% CI: 0.157–0.872, P = 0.023), longer pain-to-balloon time (OR = 1.147, 95% CI: 1.015–1.297, P = 0.028) and higher Cys-C level (OR = 10.07, 95% CI: 2.340–43.377, P = 0.002) were predictors for no-reflow. Conclusion: Cys-C might be a useful predictor for the no-reflow phenomenon after PPCI in STEMI patients. It might help to screen STEMI patients with high risk of no-reflow on admission. [ABSTRACT FROM AUTHOR]

Since both retinopathy and nephropathy are major diabetic microvascular complications, we investigated whether severity of diabetic retinopathy (DR) has adverse effects on renal function and albuminuria in the patients with type 2 diabetes mellitus (DM). We screened 2,197 adult patients with type 2 DM who had undergone fundus exam between August 2006 and February 2014. Among them, 1,592 subjects with available serial renal function and albuminuria measurement were included in the analysis. DR status was classified as no DR, non-proliferative DR (NPDR), and proliferative DR (PDR). The risk of CKD progression was assessed according to DR severity. A total of 384 (24.1%) had NPDR and 202 (12.7%) had PDR at either eye. The mean follow-up period was 5.6±2.1 years. DR was associated with lower body mass index, lower plasma hemoglobin, lower serum albumin level, longer duration of DM, poorer control of blood sugar, lower estimated glomerular filtration rate (eGFR), and greater amount of albuminuria. Interestingly, baseline DR severity was associated with faster renal function decline and greater albuminuria progression. In multivariate analysis, NPDR had 2.9 times and PDR had 16.6 times higher risk for CKD progression. Our findings showed that baseline DR severity is a prognostic factor for future CKD progression in type 2 DM patients. Therefore, clinicians must evaluate DR severity at the first visit and closely monitor renal function and albuminuria in the subjects with severe DR. [ABSTRACT FROM AUTHOR]

Induced pluripotent stem cell derived cardiomyocytes (iPSC-CM) have the potential to transform regenerative cardiac medicine and the modelling of cardiac disease. This is of particular importance in the context of diabetic cardiomyopathy where diabetic individuals exhibit reduced cardiac diastolic contractile performance in the absence of vascular disease, significantly contributing towards high cardiovascular morbidity. In this study, the capacity of iPSC-CM to act as a novel cellular model of cardiomyocytes was assessed. The diabetic phenotype is characterised by insulin resistance, therefore there was a specific focus upon metabolic parameters. Despite expressing crucial insulin signalling intermediates and relevant trafficking proteins, it was identified that iPSC-CM do not exhibit insulin-stimulated glucose uptake. iPSC-CM are spontaneously contractile however contraction mediated uptake was not found to mask any insulin response. The fundamental limitation identified in these cells was a critical lack of expression of the insulin sensitive glucose transporter GLUT4. Using comparative immunoblot analysis and the GLUT-selective inhibitor BAY-876 to quantify expression of these transporters, we show that iPSC-CM express high levels of GLUT1 and low levels of GLUT4 compared to primary cardiomyocytes and cultured adipocytes. Interventions to overcome this limitation were unsuccessful. We suggest that the utility of iPSC-CMs to study cardiac metabolic disorders may be limited by their apparent foetal-like phenotype. [ABSTRACT FROM AUTHOR]

Introduction: Liver transplant (LT) recipients have limited understanding of post-transplant chronic kidney disease (CKD) despite an excellent pre-existing framework of transplant care. This pilot study examined the efficacy and feasibility of a tailored educational and goal-setting tool in improving CKD knowledge among LT recipients with early-stage CKD. Methods: In this prospective cohort study, we administered the CKD educational and goal-setting tool to 81 LT recipients between 7/1/2016 and 12/31/2017. We excluded patients with simultaneous liver-kidney transplantation, eGFR<30 ml/min, non-English speaking, on hemodialysis or listed for kidney transplantation. The pre- and post-education knowledge scores were compared using a paired t-test. Linear regression was used to assess the independent predictors of change in knowledge score. Results: Mean age was 56.3 years, 69.1% were males, 85.2% were Caucasians and mean eGFR was 61.2 ± 20.0 ml/min. The CKD educational and goal-setting tool improved the CKD knowledge scores among LT recipients (pre: 71.8 ± 16.6%, post: 83.3 ± 10.4%; p<0.001). In an adjusted model (r2 = 0.75), those with lower pre-education knowledge scores had the most improvement in their post-education knowledge scores (β = -83.2; p<0.001). Two-thirds stated their most important self-management goal and reported motivation to follow this goal. Time spent for the CKD education was approximately 15 minutes. Conclusions: A simple LT-specific patient educational and goal-setting tool effectively improved CKD knowledge. Implementation of this tailored intervention will improve CKD awareness and may promote goal-setting in the target population. [ABSTRACT FROM AUTHOR]

Background: Unusual radiological images may delay diagnosis of pulmonary tuberculosis. This study aimed to analyze the risk factors for an atypical radiological image in patients with pulmonary tuberculosis. Methods: We retrospectively analyzed data from patients admitted to one hospital from January 2013 to December 2016 for sputum smear-positive lung tuberculosis who underwent chest computed tomography (CT) on admission. Patients whose sputum cultures were positive for general bacteria were excluded. Patient characteristics and laboratory data were compared between patients with cavity and those without and between patients with upper predominant lung involvement and those without. Results: This study included 94 (93%) of 101 patients who underwent chest CT. The non-cavity group was older, had a greater number of females, had a lower C-reactive protein (CRP) level, and had a lower glomerular filtration rate. Multivariate analysis showed that a low CRP level (OR 0.808; 95% CI 0.674–0.967; p = 0.020) significantly predicted non-cavity pulmonary tuberculosis. The non-upper predominant lung involvement group was older and had a greater number of females, poorer performance status, a higher CRP level, and a lower serum albumin level. A poor performance status (OR 2.155; 95% CI 1.257–3.693; p = 0.005) was found to significantly predict pulmonary tuberculosis with non-upper predominant lung distributions. Conclusions: A low CRP level and poor performance status were associated with non-cavity and non-upper predominant lung distribution, respectively, in patients with pulmonary tuberculosis. Tuberculosis patients with these characteristics may present unusual chest images. [ABSTRACT FROM AUTHOR]

Retinal fundus imaging is a non-invasive method that allows visualizing the structure of the blood vessels in the retina whose features may indicate the presence of diseases such as diabetic retinopathy (DR) and glaucoma. Here we present a novel method to analyze and quantify changes in the retinal blood vessel structure in patients diagnosed with glaucoma or with DR. First, we use an automatic unsupervised segmentation algorithm to extract a tree-like graph from the retina blood vessel structure. The nodes of the graph represent branching (bifurcation) points and endpoints, while the links represent vessel segments that connect the nodes. Then, we quantify structural differences between the graphs extracted from the groups of healthy and non-healthy patients. We also use fractal analysis to characterize the extracted graphs. Applying these techniques to three retina fundus image databases we find significant differences between the healthy and non-healthy groups (p-values lower than 0.005 or 0.001 depending on the method and on the database). The results are sensitive to the segmentation method (manual or automatic) and to the resolution of the images. [ABSTRACT FROM AUTHOR]