A modern web-based health promotion program for patients in Greece with diabetes 2 and obesity: an interventional study.

BACKGROUND: Health promotion programs are most beneficial in chronic diseases such as diabetes and morbid obesity, which can be positively affected by changes in attitudes, beliefs, and lifestyle. OBJECTIVES: This study aimed to develop an internet-based modern Health Promotion model using interactive online applications through continuing education and participation. METHODS: The goal was to positively impact knowledge, behavior, and quality of life for patients with obesity and/or diabetes. This is a prospective interventional study on patients with obesity or type 2 diabetes. Seventeen two patients who met the inclusion criteria were distributed randomly into two groups (control and intervention) from 2019 to 2021 in Greece. All the participants were given questionaries concerning quality of life anxiety and depression (HADS) attitudes and beliefs, knowledge about their condition and general questions to establish a baseline. A traditional health promotion model was followed for the control group. For participants in the intervention group, a web-based health promotion program was created according to the goals of the research. Participants were instructed to log on 1-2 times a week for 5-15 min, with the understanding that the research team would be monitoring their activities. The website included two knowledge games and personalized educational material based on their needs. RESULTS: The sample comprised 72 patients (36 in control and 36 in the intervention groups). The mean age was 47.8 years for the control group and 42.7 years for the intervention group (p = 0.293). Both study groups had a significant increase in knowledge score on diabetes (Control group:3,24, Intervention group 11,88 p < 0,001) and obesity (Control group:4,9, Intervention group 51,63 p < 0,001) along with a positive attitude score towards fighting obesity (Control group: 1,8, Intervention group 13,6 p < 0,001). Still, the overall change was more remarkable for the intervention group, as indicated by the significant interaction effect of the analysis. Anxiety was decreased only in the intervention group (Control group:0,11, Intervention group - 0,17 p < 0,005). Analysis for QOL during follow-up showed that Physical Health and Level of Independence was improved in both study groups but the degree of improvement was more significant in the intervention group (Control group 0,31,Intervention group 0,73 p < 0,001). Psychological Health was improved only in the intervention group, with better scores at 6 and 12 months compared to controls (Control group 0,28,Intervention group 1,42 p < 0,001). Furthermore, Social relationships were improved only in the intervention group (Control group 0,02, Intervention group 0,56 p < 0,001). CONCLUSIONS: The results of the present study showed that the participants in the intervention group showed significant improvement in knowledge, attitudes, and beliefs after using the internet as a learning tool. The intervention group also showed significantly reduced anxiety and depression arising from chronic illness. All of this resulted in an improved quality of life regarding physical Health, mental Health, and social relationships. Technology and online-based health promotion programs can revolutionize how we approach the prevention and management of chronic and terminal illnesses by improving accessibility, personalizing care, increasing engagement and motivation, improving data analysis, and disease management.

Familial Partial Lipodystrophy: Clinical Features, Genetics and Treatment in a Greek Referral Center.

Familial partial lipodystrophy (FPLD) is a rare syndrome in which a patient's phenotype is not merely dependent on the specific genetic mutation, but it is also defined by a combination of other demographic, environmental and genetic factors. In this prospective observational study in a Greek referral center, we enrolled 39 patients who fulfilled the clinical criteria of FPLD. A genetic analysis was conducted, which included sequence and deletion/duplication analyses of the LMNA and PPRARG genes, along with anthropometric and metabolic parameters. The treatment responses of patients who were eligible for treatment with metreleptin were evaluated at 3 and 12 months. In most of the patients, no significant changes were detected at the exon level, and any mutations that led to changes at the protein level were not associated with the lipodystrophic phenotype. On the contrary, various changes were detected at the intron level, especially in introns 7 and 10, whose clinical significance is considered unknown. In addition, treatment with metreleptin in specific FPLD patients significantly improved glycemic and lipidemic control, an effect which was sustained at the 12-month follow-up. More large-scale studies are necessary to clarify the genetic and allelic heterogeneity of the disease, along with other parameters which could predict treatment response.

Cardioprotection by selective SGLT-2 inhibitors in a non-diabetic mouse model of myocardial ischemia/reperfusion injury: a class or a drug effect?

Major clinical trials with sodium glucose co-transporter-2 inhibitors (SGLT-2i) exhibit protective effects against heart failure events, whereas inconsistencies regarding the cardiovascular death outcomes are observed. Therefore, we aimed to compare the selective SGLT-2i empagliflozin (EMPA), dapagliflozin (DAPA) and ertugliflozin (ERTU) in terms of infarct size (IS) reduction and to reveal the cardioprotective mechanism in healthy non-diabetic mice. C57BL/6 mice randomly received vehicle, EMPA (10 mg/kg/day) and DAPA or ERTU orally at the stoichiometrically equivalent dose (SED) for 7 days. 24 h-glucose urinary excretion was determined to verify SGLT-2 inhibition. IS of the region at risk was measured after 30 min ischemia (I), and 120 min reperfusion (R). In a second series, the ischemic myocardium was collected (10th min of R) for shotgun proteomics and evaluation of the cardioprotective signaling. In a third series, we evaluated the oxidative phosphorylation capacity (OXPHOS) and the mitochondrial fatty acid oxidation capacity by measuring the respiratory rates. Finally, Stattic, the STAT-3 inhibitor and wortmannin were administered in both EMPA and DAPA groups to establish causal relationships in the mechanism of protection. EMPA, DAPA and ERTU at the SED led to similar SGLT-2 inhibition as inferred by the significant increase in glucose excretion. EMPA and DAPA but not ERTU reduced IS. EMPA preserved mitochondrial functionality in complex I&II linked oxidative phosphorylation. EMPA and DAPA treatment led to NF-kB, RISK, STAT-3 activation and the downstream apoptosis reduction coinciding with IS reduction. Stattic and wortmannin attenuated the cardioprotection afforded by EMPA and DAPA. Among several upstream mediators, fibroblast growth factor-2 (FGF-2) and caveolin-3 were increased by EMPA and DAPA treatment. ERTU reduced IS only when given at the double dose of the SED (20 mg/kg/day). Short-term EMPA and DAPA, but not ERTU administration at the SED reduce IS in healthy non-diabetic mice. Cardioprotection is not correlated to SGLT-2 inhibition, is STAT-3 and PI3K dependent and associated with increased FGF-2 and Cav-3 expression.

Burnout Related to Diabetes Mellitus: A Critical Analysis.

Background: Diabetes burnout is a condition when a patient with diabetes feels tired from his/her disease and neglects it for a certain period or continuously. Objective: Diabetes burnout is frequent, and there is extended literature about psychosocial stress and its negative effects on health. Methods: A search for relevant studies was conducted using PubMed, Google Scholar and ResearchGate. A systematic review was conducted on the relevant articles after critical appraisal. Only publications in English were selected. The objective of this study was to evaluate the association between burnout syndrome and diabetes mellitus. Results: This article mainly focused on studies that evaluated the presence of burnout and diabetes mellitus effects. Diabetes can influence psychological health equally with somatic strength. Relatives can also express depression, guilt, fright, worry, rage, and burnout. Psychosocial job stress and extended working hours are linked with a higher possibility of myocardial infarction, diabetes mellitus, and hypertension. Conclusion: Diabetes burnout is a combination of emotions and practices, ranging from tiredness to indifference, linked with a distressing sense of hopelessness. Revealing this health condition is necessary so that preventive measures can be taken.

Diagnostic Performance of Frequency-Domain Optical Coherence Tomography to Predict Functionally Significant Left Main Coronary Artery Stenosis.

AIMS: The aim of this study was to assess the safety and diagnostic efficacy of frequency-domain optical coherence tomography (FD-OCT) in identifying functional severity of the left main coronary artery (LM) stenosis determined by fractional flow reserve (FFR). METHODS AND RESULTS: 101 patients with LM lesion (20-70% diameter stenosis angiographically) underwent FFR measurement and FD-OCT imaging of the LM. The following parameters were measured by FD-OCT in the LM: reference lumen area (RLA), reference lumen diameter (RLD), minimum lumen area (MLA), minimum lumen diameter (MLD), % lumen area stenosis, and % diameter stenosis. The LM lesions were analyzable by FD-OCT in 88/101 (87.1%) patients. FFR at maximum hyperemia was ≤0.80 in 39/88 (44.3%) patients. FFR values were correlated significantly with FD-OCT-derived LM lumen parameters. An MLA cutoff value of 5.38 mm2 had the highest sensitivity and specificity of 82% and 81%, respectively, followed by an MLD of 2.43 mm (sensitivity 77%, specificity 72%) and AS of 60% (sensitivity 72%, specificity 72%) for predicting FFR <0.80. CONCLUSIONS: FD-OCT is a safe and feasible imaging technique for the assessment of LM stenosis. An FD-OCT-derived MLA of ≤5.38 mm2 strongly predicts the functional severity of an LM lesion.

High Prevalence of Small Intestinal Bacterial Overgrowth among Functional Dyspepsia Patients.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO), characterized by either increased numbers or presence of colonic type bacteria in the small bowel has been previously described in functional dyspepsia (FD), based on breath testing. In this study, we aim to examine the prevalence of SIBO among FD patients using small bowel aspirate culture. METHODS: We prospectively enrolled outpatients fulfilling Rome IV criteria for FD. Severity of symptoms was graded using the patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) questionnaire. Patients underwent upper gastrointestinal endoscopy and duodenal fluid was aspirated in sterile traps. SIBO was defined as ≥103 colony forming units/mL of duodenal aspirate and/or presence of colonic type bacteria. Patients undergoing gastroscopy due to gastroesophageal reflux symptoms - control group (CG) - and patients with irritable bowel syndrome (IBS) fulfilling Rome IV criteria were also recruited. RESULTS: We enrolled 227 FD subjects, 30 CG, and 90 IBS patients. Among FD patients, 144 (63.4%), 64 (28.2%), and 19 (8.4%) had postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), and overlapping PDS-EPS syndrome, respectively. SIBO prevalence was 20.8%, 12.5%, and 31.6% among PDS, EPS, and overlapping PDS-EPS FD subtypes, respectively. Overall, SIBO prevalence was significantly higher in FD (44/227 [19.4%]) compared to CG (1/30 [3.3%]) (p = 0.037) and similar to IBS (44/227 [19.4%] vs. 15/90 [16.7%], p = 0.63) subjects. SIBO presence was associated neither with total nor with any subscale score of the PAGI-SYM questionnaire. CONCLUSION: In a cohort of Greek FD patients, SIBO prevalence was similar to that of IBS subjects and higher compared to that of controls.

Micronutrient dietary intakes and their food sources in adults: the Hellenic National Nutrition and Health Survey (HNNHS).

BACKGROUND: The present study aimed to assess micronutrient intake among Greek adults and to identify the main food sources that contribute to it. METHODS: Food consumption data from 2389 participants in the Hellenic National Nutrition and Health Survey (HNNHS), collected with 24-h recalls, was used to calculate micronutrient intakes. Usual nutrient intake was estimated according to the National Cancer Institute method. Nutrient adequacy was estimated using the estimated average requirement (EAR) cut-point method, when available, or adequate intake otherwise. The probability approach was used to determine iron intake adequacy in females of reproductive age. Food group contribution for each nutrient assessed was derived to identify their main food sources. RESULTS: Almost all individuals had vitamin D intake below EAR, whereas vitamins A, E, K and C, as well as potassium intake, were also insufficient in a considerable percentage of the population (>70% in most age groups). Calcium intake was substantially below the EAR for females aged >50 years and males >70 years; the same for magnesium in males >70 years. Furthermore, 50% of females, including those of reproductive age, had intake of folate below EAR. More than 50% of the population (to 79%) exceeded the upper tolerable limit for sodium (2300 mg day-1 ). Food contribution analysis revealed that most vitamins were derived from low-quality foods (i.e. fast-food). CONCLUSIONS: A significant proportion of adults residing in Greece have low nutrient intake and poor food selections. These results provide guidance to public health policy makers for developing strategies to improve the dietary quality in Greece.

Competing Effects of Renin Angiotensin System Blockade and Sodium-Glucose Cotransporter-2 Inhibitors on Erythropoietin Secretion in Diabetes.

BACKGROUND: Anaemia is a common finding in diabetes, particularly in those patients with albuminuria or renal dysfunction and is associated with impaired erythropoietin (EPO) secretion. This review focuses on mechanisms involved in the regulation of erythropoiesis in diabetic patients in an effort to elucidate the competing effects of the renin angiotensin system (RAS) blockade and sodium-glucose cotransporter-2 (SGLT2) inhibitors on haemoglobin concentration and hematocrit values. SUMMARY: The RAS shows significant activation in diabetic subjects. Angiotensin II, its active octapeptide, causes renal tubulointerstitial hypoxia, which stimulates hypoxia-inducible factors (HIF) and increases EPO secretion and erythropoiesis. As expected, drugs that inactivate RAS, such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARB) are associated with a significant hematocrit-lowering effect and/or anaemia in various clinical conditions, including diabetes. Dual blockade by a combination of ACEi and ARB in diabetic patients achieves a better RAS inhibition, but at the same time a worse drop of haemoglobin concentration. Increased glucose reabsorption by SGLTs in diabetic subjects generates a high-glucose environment in renal tubulointerstitium, which may impair HIF-1, damage renal erythropoietin-producing cells (REPs) and decrease EPO secretion and erythropoiesis. SGLT2 inhibitors, which inhibit glucose reabsorption, may attenuate glucotoxicity in renal tubulointerstitium, allowing REPs to resume their function and increase EPO secretion. Indeed, EPO levels increase within a few weeks after initiation of therapy with all known SGLT2 inhibitors, followed by increased reticulocyte count and a gradual elevation of haemoglobin concentration and hematocrit level, which reach zenith values after 2-3 months. Key Messages: The competing effects of RAS blockade and SGLT2 inhibitors on erythropoiesis may have important clinical implications. The rise of hematocrit values by SGLT2 inhibitors given on top of RAS blockade in recent outcome trials may significantly contribute to the cardiorenal protection attained. The relative contribution of each system to erythropoiesis and outcome remains to be revealed in future studies.

ß-Amyloid and mitochondrial-derived peptide-c are additive predictors of adverse outcome to high-on-treatment platelet reactivity in type 2 diabetics with revascularized coronary artery disease.

BACKGROUND AND AIMS: Increased ß-amyloid and decreased mitochondrial-derived peptide (MOTS-c), are reported in diabetes. We investigated their additive value to high on-clopidogrel platelet reactivity (HPR) for adverse outcome in type 2 diabetics after recent revascularization. PATIENTS AND METHODS: In 121 type II diabetics, treated with clopidogrel and aspirin, (93 males, mean age 67.2 years) we measured: (a) maximum platelet aggregation to adenosine diphosphate (ADP) by light transmission aggregometry (LTAmax), (b) malondialdehyde (MDA), as oxidative stress marker, (c) MOTS-c, (d) ß-amyloid blood levels. Cardiac death and acute coronary syndromes (MACE) were recorded during 2 years of follow-up. RESULTS: Out of 121 patients, 32 showed HPR (LTAmax > 48%,). At baseline, HPR was associated with ß-amyloid > 51 pg/ml (p = 0.006) after adjusting clinical variables, HbA1c, MOTS-c, MDA and medication. During follow-up, 22 patients suffered a MACE. HPR, ß-amyloid > 51 pg/ml and MOTS-c < 167 ng/ml were predictors of MACE (relative risk 3.1, 3.5 and 3.8 respectively, p < 0.05) after adjusting for confounders and medication. There was significant interaction between HPR and ß-amyloid or MOTS-c for the prediction of MACE (p < 0.05). Patients with HPR and ß-amyloid > 51 mg/dl or HPR and MOTS-c concentration < 167 ng/ml had a fourfold higher risk for MACE than patients without these predictors (relative risk 4.694 and 4.447 respectively p < 0.01). The above results were confirmed in an external validation cohort of 90 patients with diabetes and CAD. CONCLUSIONS: Increased ß-amyloid or low MOTS-c are additive predictors to high on-clopidogrel platelet reactivity for adverse outcome in diabetics with CAD during 2-years follow-up. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT04027712.

The use of sodium-glucose co-transporter 2 inhibitors in the inpatient setting: Is the risk worth taking?

WHAT IS KNOWN AND OBJECTIVE: In the outpatient setting, sodium-glucose co-transporter 2 inhibitors (SGLT2i) are recognized as effective agents to optimize glycaemia and also developing robust evidence for cardiovascular (CV) and renal protection in people with type 2 diabetes, particularly those at higher risk. However, data on the safety and efficacy of these drugs in hospitalized patients remain limited. The purpose of this review is to discuss the balance between risks and benefits of SGLT2i use in the inpatient setting. METHODS: PubMed, Embase and Google Scholar databases were searched to identify relevant published work. Available evidence on the mechanisms of action and the safety profile of SGLT2i in the context of their use in hospitalized individuals are summarized and discussed in this narrative review. RESULTS AND DISCUSSION: The rationale behind the use of these agents in the inpatient setting is based on the low risk of hypoglycaemia, the practical dosing scheme and the potential to decrease subsequent heart failure admission rates. In addition, data from animal studies indicate the ability of SGLT2i to ameliorate oxidative stress, suppress sympathetic activity, enhance autophagy and promote cardiac remodelling, when administered in the acute phase of CV episodes. On the other hand, these drugs have been linked to specific adverse events related to their mechanism of action, including an increased risk of euglycaemic diabetic ketoacidosis and volume depletion, which raises concerns over their usefulness in inpatients, particularly individuals with multimorbidities. WHAT IS NEW AND CONCLUSION: Potential benefits deriving from the use of SGLT2i in the inpatient setting cannot mitigate possible risks, at least until robust evidence on their efficacy in hospitalized individuals become available. The concept of administering these agents in the acute phase of CV episodes, in people with or without diabetes, requires further evaluation in appropriately designed clinical studies.

Take Control: A randomized trial evaluating the efficacy and safety of self- versus physician-managed titration of insulin glargine 300 U/mL in patients with uncontrolled type 2 diabetes.

AIM: To compare the efficacy and safety of self- versus physician-managed titration of insulin glargine 300 U/mL (Gla-300) in people with inadequately controlled type 2 diabetes. METHODS: Take Control (EudraCT number: 2015-001626-42) was a 24-week, multi-national, open-label, controlled, two-arm, parallel-group study in insulin-naïve and pre-treated participants, randomized 1:1 to a self- or physician-managed titration of Gla-300. The fasting self-monitored plasma glucose (SMPG) target was 4.4 to 7.2 mmol/L. The primary outcome was non-inferiority of glycated haemoglobin (HbA1c) change from baseline to week 24. Secondary outcomes included SMPG target achievement without hypoglycaemia, hypoglycaemia incidence, adverse events and participant-reported outcomes (PROs). RESULTS: At week 24, the least squares (LS) mean HbA1c reduction was 0.97% (10.6 mmol/mol) and 0.84% (9.2 mmol/mol) in the self- and physician-managed groups, respectively, with an LS mean difference of -0.13% [95% confidence interval -0.2619 to -0.0004] (-1.4 mmol/mol [-2.863 to -0.004]), demonstrating non-inferiority (P < 0.0001) and superiority (P = 0.0247) of self- versus physician-managed titration. Significantly more of the self- than physician-managed group achieved SMPG target without hypoglycaemia (67% vs 58%; P = 0.0187). Overall, hypoglycaemia incidence was similar in each group. No safety concerns were reported. In both groups, similar PRO improvements were observed for distress related to diabetes disease burden and for confidence in diabetes self-management, with even more individuals achieving a clinically relevant reduction in emotional burden and fewer individuals with high emotional burden in the self-managed group. CONCLUSIONS: Self-managed titration of Gla-300 was superior to physician-managed titration in terms of HbA1c reduction, accompanied by similar total PRO scores, with a clinically relevant reduction in emotional burden, and similar hypoglycaemia frequency.

Effect of liraglutide on ambulatory blood pressure in patients with hypertension and type 2 diabetes: A randomized, double-blind, placebo-controlled trial.

AIMS: To assess the effect of liraglutide on 24-hour ambulatory blood pressure and heart rate in patients with hypertension (pre- and stage 1 hypertension) and inadequately controlled Type 2 diabetes (glycated haemoglobin 7%-10% [53-86 mmol/mol]). MATERIALS AND METHODS: Eligible patients for this investigator-initiated, parallel-group, randomized, double-blind trial were on stable background antihyperglycaemic therapy excluding insulin, glucagon-like peptide-1 receptor agonists and dipeptidyl-peptidase-4 inhibitors. Participants were centrally randomized in a 1:1 ratio to daily liraglutide 0.6 mg, titrated to 1.2 mg after the first week, or placebo for 5 weeks. The primary outcome was change in 24-hour ambulatory systolic blood pressure (SBP), and secondary outcomes included change in ambulatory diastolic blood pressure (DBP) and heart rate. We also assessed renal sodium handling. RESULTS: Of 87 patients assessed for eligibility, 62 (66.1% men) with a mean age of 60.2 years were randomized to liraglutide (n = 31) or placebo (n = 31). All participants received background therapy with metformin, whilst 35.5% were treated concomitantly with sulphonylureas and 14.5% with pioglitazone. Compared with placebo, liraglutide reduced 24-hour SBP by -5.73 mm Hg (95% confidence interval [CI] -9.81 to -1.65) and had a neutral effect on 24-hour DBP (mean difference - 1.42 mm Hg; 95% CI -4.25 to 1.40), whilst increasing 24-hour heart rate by 6.16 beats/min (95% CI 3.25 to 9.07). Findings were consistent for daytime and night-time measurements. Liraglutide did not increase urine sodium excretion. CONCLUSION: Based on 24-hour ambulatory measurements, short-term treatment with liraglutide had a favourable effect on SBP whilst increasing heart rate.

Problem Gambling in Greece: Prevalence and Risk Factors During the Financial Crisis.

In Greece no study has ever been conducted on the prevalence of problem gambling. Therefore, a cross-sectional survey was carried out amid the recession aiming to (1) estimate past year prevalence of problem gambling, (2) explore socio-economic and demographic differences among gamblers and non gamblers, (3) explore socio-economic and demographic differences among gamblers who started gambling prior and during the downturn and (4) identify its risk factors with a special interest in the influence of the recession. To this end, data emanating from a telephone and patron survey were combined. A random and representative sample of 3.404 people participated in the telephone survey and 2.400 in the patron survey. The interview schedule was the same in both studies. The presence of problem gambling was assessed with the Canadian Problem Gambling Index. Information on participants' socio-economic and demographic characteristics as well as their ways of dealing financially with the crisis were collected. Findings indicated that 2.4% of respondents met criteria for problem gambling. Male gender, minority status, living with family of origin, low educational level and low to zero income were found to constitute the risk factors of the disorder. Moreover, having started gambling during the recession increased the odds of suffering from problem gambling; however this finding was gender-specific. Thus, people end up in problem gambling through various pathways, with these trajectories being different for men and women. Any intervention should address the complexity of the issue and be tailored by gender.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Metabolic Disease or Disturbed Homeostasis due to Focal Inflammation in the Hypothalamus?

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease characterized by debilitating fatigue, lasting for at least 6 months, with associated malaise, headaches, sleep disturbance, and cognitive impairment, which severely impacts quality of life. A significant percentage of ME/CFS patients remain undiagnosed, mainly due to the complexity of the disease and the lack of reliable objective biomarkers. ME/CFS patients display decreased metabolism and the severity of symptoms appears to be directly correlated to the degree of metabolic reduction that may be unique to each individual patient. However, the precise pathogenesis is still unknown, preventing the development of effective treatments. The ME/CFS phenotype has been associated with abnormalities in energy metabolism, which are apparently due to mitochondrial dysfunction in the absence of mitochondrial diseases, resulting in reduced oxidative metabolism. Such mitochondria may be further contributing to the ME/CFS symptomatology by extracellular secretion of mitochondrial DNA, which could act as an innate pathogen and create an autoinflammatory state in the hypothalamus. We propose that stimulation of hypothalamic mast cells by environmental, neuroimmune, pathogenic and stress triggers activates microglia, leading to focal inflammation in the brain and disturbed homeostasis. This process could be targeted for the development of novel effective treatments.

The impact of oral anti-diabetic medications on heart failure: lessons learned from preclinical studies.

The prevalence of heart failure (HF) in the diabetic population has rapidly increased over the past 2 decades, triggering research about the impact of oral anti-diabetic medications on it. Unfortunately, not all success at the bench in preclinical experiments has translated to success at the bedside. On the other hand, recent promising clinical data from oral SGLT2 inhibitors mainly lack mechanistic explanation from experimental studies. Hence, it is critical to understand the lessons learned from prior translational studies to gain a better knowledge of the mechanisms of oral anti-diabetic drugs in HF. This review aims to summarize the results from preclinical studies regarding the interaction between oral anti-diabetic medications and heart failure development and/or exacerbation. Although there is a wide spectrum of controversial results, the underlying hope is that the clinical success rate will improve and the adverse events during ineffective targeted therapy will be limited.

Possible mechanisms of direct cardiovascular impact of GLP-1 agonists and DPP4 inhibitors.

Diabetes mellitus is a leading cause of cardiovascular morbidity and mortality worldwide. Traditional antidiabetic therapies targeting hyperglycemia reduce diabetic microvascular complications but have minor effects on macrovascular complications, including cardiovascular disease. Instead, cardiovascular complications are improved by antidiabetic medications (metformin) and other therapies (statins, antihypertensive medications) ameliorating insulin resistance and other associated metabolic abnormalities. Novel classes of antidiabetic drugs have proven efficacious in improving glycemia, while at the same time exert beneficial effects on pathophysiologic mechanisms of diabetes-related cardiovascular disease. In the present review, we will present current evidence of the cardiovascular effects of two new classes of antidiabetic medications, glucagon-like peptide 1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP4) inhibitors, focusing from mechanistic preclinical and clinical investigation to late-phase clinical testing.

Effects of 6-month treatment with the glucagon like peptide-1 analogue liraglutide on arterial stiffness, left ventricular myocardial deformation and oxidative stress in subjects with newly diagnosed type 2 diabetes.

BACKGROUND: Incretin-based therapies are used in the treatment of type 2 diabetes mellitus (T2DM) and obesity. We investigated the changes in arterial stiffness and left ventricular (LV) myocardial deformation after 6-month treatment with the GLP-1 analogue liraglutide in subjects with newly diagnosed T2DM. METHODS: We randomized 60 patients with newly diagnosed and treatment-naive T2DM to receive either liraglutide (n = 30) or metformin (n = 30) for 6 months. We measured at baseline and after 6-month treatment: (a) carotid-femoral pulse wave velocity (PWV) (b) LV longitudinal strain (GLS), and strain rate (GLSR), peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography. LV untwisting was calculated as the percentage difference between peak twisting and untwisting at MVO (%dpTw-UtwMVO), at peak (%dpTw-UtwPEF) and end of early LV diastolic filling (%dpTw-UtwEDF) (c) Flow mediated dilatation (FMD) of the brachial artery and percentage difference of FMD (FMD%) (d) malondialdehyde (MDA), protein carbonyls (PCs) and NT-proBNP. RESULTS: After 6-months treatment, subjects that received liraglutide presented with a reduced PWV (11.8 ± 2.5 vs. 10.3 ± 3.3 m/s), MDA (0.92 [0.45-2.45] vs. 0.68 [0.43-2.08] nM/L) and NT-proBNP (p < 0.05) in parallel with an increase in GLS (- 15.4 ± 3 vs. - 16.6 ± 2.7), GLSR (0.77 ± 0.2 vs. 0.89 ± 0.2), pUtwVel (- 97 ± 49 vs. - 112 ± 52°, p < 0.05), %dpTw-UtwMVO (31 ± 10 vs. 40 ± 14), %dpTw-UtwPEF (43 ± 19 vs. 53 ± 22) and FMD% (8.9 ± 3 vs. 13.2 ± 6, p < 0.01). There were no statistically significant differences of the measured markers in subjects that received metformin except for an improvement in FMD. In all subjects, PCs levels at baseline were negatively related to the difference of GLS (r = - 0.53) post-treatment and the difference of MDA was associated with the difference of PWV (r = 0.52) (p < 0.05 for all associations) after 6-month treatment. CONCLUSIONS: Six-month treatment with liraglutide improves arterial stiffness, LV myocardial strain, LV twisting and untwisting and NT-proBNP by reducing oxidative stress in subjects with newly diagnosed T2DM. ClinicalTrials.gov Identifier NCT03010683.

t-SNE Visualization of Large-Scale Neural Recordings.

Electrophysiology is entering the era of big data. Multiple probes, each with hundreds to thousands of individual electrodes, are now capable of simultaneously recording from many brain regions. The major challenge confronting these new technologies is transforming the raw data into physiologically meaningful signals, that is, single unit spikes. Sorting the spike events of individual neurons from a spatiotemporally dense sampling of the extracellular electric field is a problem that has attracted much attention (Rey, Pedreira, & Quian Quiroga, 2015 ; Rossant et al., 2016 ) but is still far from solved. Current methods still rely on human input and thus become unfeasible as the size of the data sets grows exponentially. Here we introduce the [Formula: see text]-student stochastic neighbor embedding (t-SNE) dimensionality reduction method (Van der Maaten & Hinton, 2008 ) as a visualization tool in the spike sorting process. t-SNE embeds the [Formula: see text]-dimensional extracellular spikes ([Formula: see text] = number of features by which each spike is decomposed) into a low- (usually two-) dimensional space. We show that such embeddings, even starting from different feature spaces, form obvious clusters of spikes that can be easily visualized and manually delineated with a high degree of precision. We propose that these clusters represent single units and test this assertion by applying our algorithm on labeled data sets from both hybrid (Rossant et al., 2016 ) and paired juxtacellular/extracellular recordings (Neto et al., 2016 ). We have released a graphical user interface (GUI) written in Python as a tool for the manual clustering of the t-SNE embedded spikes and as a tool for an informed overview and fast manual curation of results from different clustering algorithms. Furthermore, the generated visualizations offer evidence in favor of the use of probes with higher density and smaller electrodes. They also graphically demonstrate the diverse nature of the sorting problem when spikes are recorded with different methods and arise from regions with different background spiking statistics.

Meta-analysis of randomized controlled trials challenging the usefulness of purgative preparation before small-bowel video capsule endoscopy.

BACKGROUND: The usefulness of purgative preparation before small-bowel video capsule endoscopy is controversial. We aimed to examine the effect of purgative preparation on small-bowel video capsule endoscopy outcomes. METHODS: We performed literature searches in MEDLINE and the Cochrane library for randomized controlled trials evaluating the effect of purgative preparation (polyethylene glycol, sodium phosphate, others) vs. clear-liquid diet/fasting in patients undergoing small-bowel capsule endoscopy. Meta-analysis outcomes included the examination's diagnostic yield, small-bowel mucosal visualization quality, the examination's completion rate, and gastric and small-bowel transit times. The effect size on study outcomes was calculated using a fixed- or random-effect model, as appropriate, and is shown as the risk ratio (RR) with 95 % confidence interval (CI). RESULTS: We identified 12 eligible trials with 17 sets of data including 1221 subjects. Significant heterogeneity was detected with no evidence of publication bias. As compared with clear-liquid diet, purgative bowel preparation did not increase capsule endoscopy diagnostic yield (RR 1.17 [95 %CI 0.97 to 1.40]; P = 0.11). Neither the small-bowel mucosal visualization quality (RR 1.14 [95 %CI 0.96 to 1.35]; P = 0.15) nor completion rate for the examination (RR 0.99 [95 %CI 0.95 to 1.04]; P = 0.76) significantly improved after purgative preparation. Purgatives also had no effect on video capsule endoscopy gastric and small-bowel transit times. CONCLUSIONS: Our analysis challenges the usefulness of purgative preparation for improving the diagnostic yield of small-bowel video capsule endoscopy and the quality of small-bowel mucosal visualization.

PCOS remains a diagnosis of exclusion: a concise review of key endocrinopathies to exclude.

Polycystic ovarian syndrome (PCOS) is a heterogenous disorder associated with clinical, endocrine and ultrasonographic features that can also be encountered in a number of other diseases. It has traditionally been suggested that prolactin excess, enzymatic steroidogenic abnormalities and thyroid disorders need to be excluded before a diagnosis of PCOS is made. However, there is paucity of data regarding the prevalence of PCOS phenotype in some of these disorders, whereas other endocrine diseases that exhibit PCOS-like features may elude diagnosis and proper management if not considered. This article reviews the data of currently included entities that exhibit a PCOS phenotype and those that potentially need to be looked for, and attempts to identify specific features that distinguish them from idiopathic PCOS.