There is strong support among smokers in Pakistan to strengthen tobacco control. Given this, policy-makers should strongly consider strengthening existing national policies on tobacco control.There is strong support among smokers in Pakistan to strengthen tobacco control. Given this, policy-makers should strongly consider strengthening existing national policies on tobacco control. Recent studies indicate that sodium-glucose cotransporter 2 (SGLT-2) inhibition increases endogenous glucose production (EGP), potentially counteracting the glucose-lowering potency, and stimulates lipid oxidation and lipolysis. However, the acute effects of SGLT-2 inhibition on hepatic glycogen, lipid, and energy metabolism have not yet been analyzed. We therefore investigated the impact of a single dose of dapagliflozin (D) or placebo (P) on hepatic glycogenolysis, hepatocellular lipid (HCL) content and mitochondrial activity ( ATP). Ten healthy volunteers (control [CON] age 30 ± 3 years, BMI 24 ± 1 kg/m , HbA 5.2 ± 0.1%) and six patients with type 2 diabetes mellitus (T2DM age 63 ± 4 years, BMI 28 ± 1.5 kg/m , HbA 6.1 ± 0.5%) were investigated on two study days (CON-P vs. CON-D and T2DM-P vs. T2DM-D). H/ C/ P MRS was performed before, 90-180 min (MR1), and 300-390 min (MR2) after administration of 10 mg dapagliflozin or placebo. EGP was assessed by tracer dilution techniques. Compared withakdown. HCL and ATP are not significantly affected by a single dose of dapagliflozin.The rise in EGP after SGLT-2 inhibition is due to increased gluconeogenesis, but not glycogenolysis. Changes in glucagon and the insulin-to-glucagon ratio are not associated with an increased hepatic glycogen breakdown. HCL and kATP are not significantly affected by a single dose of dapagliflozin. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk for heart failure hospitalization potentially by inducing sodium excretion, osmotic diuresis, and plasma volume contraction. Few studies have investigated this hypothesis, but none have assessed cumulative sodium excretion with SGLT2 inhibition during standardized sodium intake in patients with type 2 diabetes. The DAPASALT trial was a mechanistic, nonrandomized, open-label study in patients with type 2 diabetes with preserved kidney function on a controlled standardized sodium diet (150 mmol/day). It evaluated the effects of dapagliflozin on sodium excretion, 24-h blood pressure, and extracellular, intracellular, and plasma volumes at the start of treatment (ST) (days 2-4), end of treatment (ET) (days 12-14), and follow-up (FU) (days 15-18). Fourteen patients were included in the efficacy analysis. Adenosine disodium triphosphate manufacturer Mean (SD) baseline sodium excretion (150 [32] mmol/24-h) did not significantly change during treatment (change at ST -7.0 mmol/24-h [95% CI -22.4, 8.4]; change at ET 2.1 mmol/24-h [-28.8, 33.0]). Mean baseline 24-h systolic blood pressure was 128 (10) mmHg and significantly reduced at ST (-6.1 mmHg [-9.1, -3.1]; < 0.001) and ET (-7.2 mmHg [-10.0, -4.3]; < 0.001). Dapagliflozin did not significantly alter plasma volume or intracellular volume, while extracellular volume changed at ST (-0.7 L [-1.3, -0.1]; = 0.02). As expected, 24-h urinary glucose excretion significantly increased during dapagliflozin treatment and reversed during FU. During standardized sodium intake, dapagliflozin reduced blood pressure without clear changes in urinary sodium excretion, suggesting that factors other than natriuresis and volume changes may contribute to the blood pressure-lowering effects.During standardized sodium intake, dapagliflozin reduced blood pressure without clear changes in urinary sodium excretion, suggesting that factors other than natriuresis and volume changes may contribute to the blood pressure-lowering effects. Increased health care use and costs have been reported in individuals with diabetes with comorbid depression. Knowledge regarding cost differences between individuals with diabetes alone and those with diabetes and diagnosed/undiagnosed depression is, however, scarce. We therefore compared use and costs for patients with diabetes and no depression and patients with diabetes and documented depression diagnosis or self-reported depression symptoms for several cost components, including mental health care costs. Data from a 2013 cross-sectional survey of randomly sampled members of a nationwide German statutory health insurance (SHI) provider with diabetes ( = 1,634) were linked individually with SHI data covering four quarters before and after the survey. Self-reported depression symptoms were assessed with the Patient Health Questionnaire-9, with depression diagnosis taken from SHI data. We analyzed health care use and costs, using regression analysis to calculate cost ratios (CRs) with adjustment for sots for mental health services were rather low. Delirium is a potentially preventable disorder characterised by acute disturbances in attention and cognition with fluctuating severity. Postoperative delirium is associated with prolonged intensive care unit and hospital stay, cognitive decline and mortality. The development of biomarkers for tracking delirium could potentially aid in the early detection, mitigation and assessment of response to interventions. Because sleep disruption has been posited as a contributor to the development of this syndrome, expression of abnormal electroencephalography (EEG) patterns during sleep and wakefulness may be informative. Here we hypothesise that abnormal EEG patterns of sleep and wakefulness may serve as predictive and diagnostic markers for postoperative delirium. Such abnormal EEG patterns would mechanistically link disrupted thalamocortical connectivity to this important clinical syndrome. P-DROWS-E (Prognosticating Delirium Recovery Outcomes Using Wakefulness and Sleep Electroencephalography) is a 220-patient prospective observational study. Patient eligibility criteria include those who are English-speaking, age 60 years or older and undergoing elective cardiac surgery requiring cardiopulmonary bypass. EEG acquisition will occur 1-2 nights preoperatively, intraoperatively, and up to 7 days postoperatively. Concurrent with EEG recordings, two times per day postoperative Confusion Assessment Method (CAM) evaluations will quantify the presence and severity of delirium. EEG slow wave activity, sleep spindle density and peak frequency of the posterior dominant rhythm will be quantified. Linear mixed-effects models will be used to evaluate the relationships between delirium severity/duration and EEG measures as a function of time. P-DROWS-E is approved by the ethics board at Washington University in St. Louis. Recruitment began in October 2018. Dissemination plans include presentations at scientific conferences, scientific publications and mass media. NCT03291626.NCT03291626.