Dysfunctional high-density lipoproteins in type 2 diabetes mellitus: Molecular mechanisms and therapeutic implications

High density lipoproteins (HDLs) are commonly known for their anti-atherogenic properties that include functions such as the promotion of cholesterol efflux and reverse cholesterol transport, as well as antioxidant and anti-inflammatory activities. However, because of some chronic inflammatory diseases, such as type 2 diabetes mellitus (T2DM), significant changes occur in HDLs in terms of both structure and composition. These alterations lead to the loss of HDLs’ physiological functions, to transformation into dysfunctional lipoproteins, and to increased risk of cardiovascular disease (CVD). In this review, we describe the main HDL structural/functional alterations observed in T2DM and the molecular mechanisms involved in these T2DM-derived modifications. Finally, the main available therapeutic interventions targeting HDL in diabetes are discussed

Statin short-term inhibition of insulin sensitivity and secretion during acute phase of ST-elevation myocardial infarction

Hyperglycemia during myocardial infarction (MI) has a strong and direct association with mortality. In stable patients and experimental models, statins favor the elevation of glycaemia. The present study investigated whether short-course treatment with statins during MI can influence glucose homeostasis and thus the clinical outcome. In this prospective study, euglycemic hyperinsulinemic clamp (EHC) was performed at second (D2) and sixth (D6) day after MI in patients randomized to simvastatin (S)10 or 80 mg/day during hospitalization (n = 27). In addition, patients (n = 550) were treated without (WS) or with simvastatin (S) at 20, 40 or 80 mg/day had HOMA2S on admission (D1) and fifth (D5) day after MI. According to EHC, insulin sensitivity increased by 20 +/- 60% in S10 and decreased by -6 +/- 28% in S80 (p = 0.025). Consistently, the changes in HOMA2S between D1 and D5 were 40 +/- 145% (WS), 22 +/- 117% (S20), 16 +/- 61% (S40) and -2% +/- 88% (S80) (p = 0.001). In conclusion, statin during the acute phase of MI reduces insulin sensitivity in a dose-dependent manner.9CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ301465/2017-

Crossmodal representation of a functional robotic hand arises after extensive training in healthy participants

The way in which humans represent their own bodies is critical in guiding their interactions with the environment. To achieve successful body-space interactions, the body representation is strictly connected with that of the space immediately surrounding it through efficient visuo-tactile crossmodal integration. Such a body-space integrated representation is not fixed, but can be dynamically modulated by the use of external tools. Our study aims to explore the effect of using a complex tool, namely a functional prosthesis, on crossmodal visuo-tactile spatial interactions in healthy participants. By using the crossmodal visuo-tactile congruency paradigm, we found that prolonged training with a mechanical hand capable of distal hand movements and providing sensory feedback induces a pattern of interference, which is not observed after a brief training, between visual stimuli close to the prosthesis and touches on the body. These results suggest that after extensive, but not short, training the functional prosthesis acquires a visuo-tactile crossmodal representation akin to real limbs. This finding adds to previous evidence for the embodiment of functional prostheses in amputees, and shows that their use may also improve the crossmodal combination of somatosensory feedback delivered by the prosthesis with visual stimuli in the space around it, thus effectively augmenting the patients' visuomotor abilities

Omega-3 intake is associated with attenuated inflammatory response and cardiac remodeling after myocardial infarction

Myocardial infarction (MI) elicits an intense acute inflammatory response that is essential for cardiac repair. However, an excessive inflammatory response also favors myocardial apoptosis, cardiac remodeling, and cardiovascular mortality. Omega-3 polyunsaturated fatty acids (-3) bear anti-inflammatory effects, which may mitigate the inflammatory response during MI. This study investigated whether -3 intake is associated with attenuation of the MI-related inflammatory response and cardiac remodeling. ST-elevation MI (STEMI) patients (n=421) underwent clinical, biochemical, nutritional, 3D echocardiogram, Cardiac Magnetic Resonance imaging (CMRi) at 30 days and 3D echocardiogram imaging at six months after the MI. Blood tests were performed at day one (D1) and day five (D5) of hospitalization. Changes in inflammatory markers (D5-D1) were calculated. A validated food frequency questionnaire estimated the nutritional consumption and -3 intake in the last 3months before admission. The intake of -3 below the median (<1.7g/day) was associated with a short-term increase in hs-C-reactive protein [OR:1.96(1.24-3.10); p=0.004], Interleukin-2 [OR:2.46(1.20-5.04); p=0.014], brain-type natriuretic peptide [OR:2.66(1.30-5.44); p=0.007], left-ventricle end-diastolic volume [OR:5.12(1.11-23.52)]; p=0.036] and decreases in left-ventricle ejection fraction [OR:2.86(1.47-6.88); p=0.017] after adjustment for covariates. No differences were observed in the extension of infarcted mass obtained by CMRi. These findings suggest that a reduced daily intake of -3 may intensify outcome-determining mechanisms after STEMI, such as acute inflammatory response and late left ventricular remodeling.18CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ308550/2010-

Downy mildew warning systems for vineyards cultivated under plastic covering - influence on yield and quality

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Competing risk analysis on outcome after hepatic resection of hepatocellular carcinoma in cirrhotic patients

To investigate death for liver failure and for tumor recurrence as competing events after hepatectomy of hepatocellular carcinoma. METHODS Data from 864 cirrhotic Child-Pugh class A consecutive patients, submitted to curative hepatectomy (1997-2013) at two tertiary referral hospitals, were used for competing-risk analysis through the Fine and Gray method, aimed at assessing in which circumstances the oncological benefit from tumour removal is greater than the risk of dying from hepatic decompensation. To accomplish this task, the average risk of these two competing events, over 5 years of follow-up, was calculated through the integral of each cumulative incidence function, and represented the main comparison parameter. RESULTS Within a median follow-up of 5.6 years, death was attributable to tumor recurrence in 63.5%, and to liver failure in 21.2% of cases. In the first 16 mo, the risk of dying due to liver failure exceeded that of dying due to tumor relapse. Tumor stage only affects death from recurrence; whereas hepatitis C infection, Model for End-stage Liver Disease score, extent of hepatectomy and portal hypertension influence death from liver failure (P < 0.05 in all cases). The combination of these clinical and tumoral features identifies those patients in whom the risk of dying from liver failure did not exceed the tumour-related mortality, representing optimal surgical candidates. It also identifies those clinical circumstances where the oncological benefit would be borderline or even where the surgery would be harmful. CONCLUSION Having knowledge of these competing events can be used to weigh the risks and benefits of hepatic resection in each clinical circumstance, separating optimal from non-optimal surgical candidates

Development of a prognostic score to predict response to Yttrium-90 radioembolization for hepatocellular carcinoma with portal vein invasion

Background & Aims: Yttrium-90 transarterial radioembolization (TARE) has shown promising efficacy in the treatment of patients with hepatocellular carcinoma (HCC), associated with portal vein tumor thrombus (PVTT). The aim of this study is to identify prognostic factors for survival in patients with HCC and PVTT undergoing TARE, and build a prognostic classification for these patients. Methods: This is a single center retrospective study conducted over six years (2010-2015), on consecutive patients undergoing TARE. Patients were included if they met the following criteria: presence of at least one measurable HCC, presence of PVTT not occluding the main portal trunk, absence of extrahepatic metastases, Child-Pugh score within B7, Eastern Cooperative Oncology Group performance status 0-1. Uni- and multivariable analysis was used to explore the variables that showed an independent relationship with survival. A prognostic score was then derived, and three prognostic categories were identified. Results: A total of 120 patients were included in the study. Median overall survival (OS) was 14.1 months (95% CI 10.7-17.5) and median progression-free survival (PFS) was 6.5 months (95% CI 3.8-9.2). The only variables independently correlated with OS were bilirubin, extension of PVTT and tumor burden. Three prognostic categories were identified: favourable prognosis (0 points), intermediate prognosis (2-3 points) and dismal prognosis (>3 points). Median OS in the three categories was 32.2 months, 14.9 months and 7.8 months respectively (p <0.0001). PFS (p = 0.045) and the risk of liver decompensation (p <0.0001) also significantly differed along the same prognostic categories. Conclusions: Radioembolization with Yttrium-90 is an effective therapy for patients with HCC and PVTT. The proposed prognostic stratification may help to better identify good candidates for the treatment, and those for whom TARE may be futile. Lay summary: Yttrium-90 transarterial radioembolization (TARE) is a microembolic procedure that minimizes alterations to hepatic arterial flow, and thus can be safely performed in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). In this study, we retrospectively evaluated the independent predictors of long-term outcomes in patients with HCC and PVTT treated with TARE. Bilirubin level, extension of PVTT and tumor burden were independently related to post-treatment survival: the combination of these factors allowed us to build a prognostic stratification that may help to better identify good candidates for the treatment, and those for whom TARE may be futile. (C) 2018 European Association for the Study of the Liver. d