Multi-scale analysis of radio-frequency performance of 2D-material based field-effect transistors.

Two-dimensional materials (2DMs) are a promising alternative to complement and upgrade high-frequency electronics. However, in order to boost their adoption, the availability of numerical tools and physically-based models able to support the experimental activities and to provide them with useful guidelines becomes essential. In this context, we propose a theoretical approach that combines numerical simulations and small-signal modeling to analyze 2DM-based FETs for radio-frequency applications. This multi-scale scheme takes into account non-idealities, such as interface traps, carrier velocity saturation, or short channel effects, by means of self-consistent physics-based numerical calculations that later feed the circuit level via a small-signal model based on the dynamic intrinsic capacitances of the device. At the circuit stage, the possibilities range from the evaluation of the performance of a single device to the design of complex circuits combining multiple transistors. In this work, we validate our scheme against experimental results and exemplify its use and capability assessing the impact of the channel scaling on the performance of MoS2-based FETs targeting RF applications.

The effect of weight loss and exercise on Health-Related Quality of Life (HRQOL) following Endoscopic Bariatric Therapies (EBT) for obesity.

INTRODUCTION: Endoscopic bariatric therapies (EBT) have demonstrated to induce weight loss and improve comorbidities in obese patients. However, little is known about its impact on health-related quality of life (HRQOL) outcomes and physical activity status. This study aimed to evaluate the change in HRQOL and physical activity following EBT induced weight loss in obese patients. METHODS: We approached 181 patients who underwent EBT in a standardized multidisciplinary follow-up program to participate in the study. We provided them two questionnaires-a) Short Form-36 health survey with the physical (PSC) and mental (MSC) summary component scores to capture generic HRQOL, and b) international physical activity questionnaire (IPAQ) for physical activity (PA). We administered the survey at baseline and at 9 months post-procedure. We expressed the procedure outcome as percentage total body weight loss (%TBWL). We expressed continuous variables as mean (SD) or median and categorical variables as percentages. We used non-parametric tests for comparison and performed multivariable linear regression analysis to identify factors associated with improvement in HRQOL. RESULTS: The mean age was 42.2 (11.3) years, and the mean BMI was 38 (5.9)kg/m2. A majority of them were female (n-132, 73%). The EBT included intragastric balloons (n-136, 75%) and endoscopic sleeve gastroplasty (n-24, 25%). The mean %TBWL achieved after the intervention was 16.9 (9.7)%. We noticed a significant improvement in the median PSC (77.8 vs. 90.4, p < 0.001) and MSC (67 vs. 80.2, p < 0.001) scores after EBT. Similarly, we observed a significant positive change in physical activity compared to baseline (1606.2 vs. 2749 MET-minutes/week, p = < 0.001). Linear regression analysis showed an increase in %TBWL was associated with significant improvement in PSC (ß = 0.193, p = 0.003) and MSC (ß = 0.166, p = 0.02) scores of HRQOL, and likewise, increase in PA was independently associated with improvement in MSC (ß = 0.192, p = 0.01). We did not find any difference in outcome based on gender or the type of intervention. CONCLUSION: EBT improves HRQOL in obese patients regardless of the type of intervention. The weight loss induced by EBT and the improvement in PA positively influence the health outcomes and quality of life.

Multifunctional targets of dietary polyphenols in disease: a case for the chemokine network and energy metabolism.

Chronic, non-acute inflammation is behind conditions that represent most of the disease burden in humans and is clearly linked to immune and metabolic mechanisms. The convergence of pathways involving the immune response, oxidative stress, increased circulating lipids and aberrant insulin signaling results in CCL2-associated macrophage recruitment and altered energy metabolism. The CCL2/CCR2 pathway and the energy sensor AMP-activated protein kinase (AMPK) are attractive therapeutic targets as a part of preventive management of disease. Several effects of polyphenols are useful in this scenario, including a reduction in the activities of cytokines and modulation of cellular metabolism through histone deacetylase inhibitors, AMPK activators, calorie-restriction mimetics or epigenetic regulators. Research is currently underway to develop orally active drugs with these effects, but it is convenient to examine more closely what we are eating. If a lack of relevance in terms of toxicity and substantial effectiveness are confirmed, plant-derived components may provide useful druggable components and dietary supplements. We consider therapeutic actions as a combination of synergistic and/or antagonistic interactions in a multi-target strategy. Hence, improvement in food through enrichment with polyphenols with demonstrated activity may represent a major advance in the design of diets with both industrial and sanitary value.

Metformin: a cheap and well-tolerated drug that provides benefits for viral infections.

OBJECTIVES: Insulin resistance in viral infections is common. We have explored the effectiveness of metformin for alleviating insulin resistance in HIV-infected patients and assessed the relevance of the ataxia-telangiectasia mutated (ATM) rs11212617 variant in the clinical response with the rationale that metformin modulates cellular bioenergetics in an ATM-dependent process. METHODS: HIV-infected patients (n = 385) were compared with controls recruited from the general population (n = 300) with respect to the genotype distribution of the ATM rs11212617 variant and its influence on selected metabolic and inflammatory variables. We also followed up a subset of male patients with HIV and hepatitis C virus (HCV) coinfection (n = 47) who were not receiving antiviral treatment and for whom metformin was prescribed for insulin resistance, which tends to have a higher incidence and severity in coinfected patients. RESULTS: Among the HIV-infected patients, human cytomegalovirus (91.9%) and HCV (62.3%) coinfections were frequent. Selected metabolic and/or inflammatory variables were significantly altered in infected patients. Treatment with metformin in HIV and HCV coinfected patients was well tolerated and significantly increased the sensitivity of peripheral tissues to insulin. The minor allele (C) of the rs11212617 variant was associated with treatment success and may affect the course of insulin resistance in response to metformin (odds ratio 1.21; 95% confidence interval 1.07-1.39; P = 0.005). There were no differences between treated and untreated patients in viral loads or variables measuring immune defence, indicating that toxicity is unlikely. CONCLUSIONS: We provide novel data suggesting that identification of the ATM rs11212617 variant may be important in assessing the glycaemic response to metformin treatment for insulin resistance in HIV-infected patients.

The role of combined assessment of defense against oxidative stress and inflammation in the evaluation of peripheral arterial disease.

Atherosclerosis in symptomatic peripheral arterial disease affects wide portions of numerous arteries in lower extremities. The resulting active inflammation in a considerable amount of arterial tissue facilitates systemic detection via measurement of inflammation-related variables. We reasoned that the combined assessment of defense against oxidative stress, in the form of paraoxonase-1 (PON1), and monocyte migration measured as circulating (C-C motif) ligand 2 (CCL2), may play a role in the evaluation of these patients. Plasma CCL2 and serum PON1-related variables, assessed by their interaction with functional genetic variants, were measured in a cross-sectional study in patients with symptomatic PAD. We found that PON1 activity and concentration were significantly lower and CCL2 concentration higher in PAD patients compared to controls, that the combination of plasma CCL2 and PON1- related values, especially PON1 concentration differentiated, almost perfectly, controls from patients and that the expression of CCL2 and PON1 generally co-localized in the atherosclerotic lesion. Since no association with genetic variants was found, such a relationship is probably the result of the disease. Our data suggest a coordinated role between CCL2 and PON1 that may be detected in blood with simple measurements and may represent an indicator of the extent of atherosclerosis.

Continuous administration of polyphenols from aqueous rooibos (Aspalathus linearis) extract ameliorates dietary-induced metabolic disturbances in hyperlipidemic mice.

The incidence of obesity and related metabolic diseases is increasing globally. Current medical treatments often fail to halt the progress of such disturbances, and plant-derived polyphenols are increasingly being investigated as a possible way to provide safe and effective complementary therapy. Rooibos (Aspalathus linearis) is a rich source of polyphenols without caloric and/or stimulant components. We have tentatively characterized 25 phenolic compounds in rooibos extract and studied the effects of continuous aqueous rooibos extract consumption in mice. The effects of this extract, which contained 25% w/w of total polyphenol content, were negligible in animals with no metabolic disturbance but were significant in hyperlipemic mice, especially in those in which energy intake was increased via a Western-type diet that increased the risk of developing metabolic complications. In these mice, we found hypolipemiant activity when given rooibos extract, with significant reductions in serum cholesterol, triglyceride and free fatty acid concentrations. Additionally, we found changes in adipocyte size and number as well as complete prevention of dietary-induced hepatic steatosis. These effects were not related to changes in insulin resistance. Among other possible mechanisms, we present data indicating that the activation of AMP-activated protein kinase (AMPK) and the resulting regulation of cellular energy homeostasis may play a significant role in these effects of rooibos extract. Our findings suggest that adding polyphenols to the daily diet is likely to help in the overall management of metabolic diseases.

Nonconcordance between subclinical atherosclerosis and the calculated Framingham risk score in HIV-infected patients: relationships with serum markers of oxidation and inflammation.

OBJECTIVES: HIV-infected patients show an increased cardiovascular disease (CVD) risk resulting, essentially, from metabolic disturbances related to chronic infection and antiretroviral treatments. The aims of this study were: (1) to evaluate the agreement between the CVD risk estimated using the Framingham risk score (FRS) and the observed presence of subclinical atherosclerosis in HIV-infected patients; (2) to investigate the relationships between CVD and plasma biomarkers of oxidation and inflammation. METHODS: Atherosclerosis was evaluated in 187 HIV-infected patients by measuring the carotid intima-media thickness (CIMT). CVD risk was estimated using the FRS. We also measured the circulating levels of interleukin-6, monocyte chemoattractant protein-1 (MCP-1) and oxidized low-density lipoprotein (LDL), and paraoxonase-1 activity and concentration. RESULTS: There was a weak, albeit statistically significant, agreement between FRS and CIMT (kappa=0.229, P<0.001). A high proportion of patients with an estimated low risk had subclinical atherosclerosis (n=66; 56.4%). In a multivariate analysis, the presence of subclinical atherosclerosis in this subgroup of patients was associated with age [odds ratio (OR) 1.285; 95% confidence interval (CI) 1.084-1.524; P=0.004], body mass index (OR 0.799; 95% CI 0.642-0.994; P=0.044), MCP-1 (OR 1.027; 95% CI 1.004-1.050; P=0.020) and oxidized LDL (OR 1.026; 95% CI 1.001-1.051; P=0.041). CONCLUSION: FRS underestimated the presence of subclinical atherosclerosis in HIV-infected patients. The increased CVD risk was related, in part, to the chronic oxidative stress and inflammatory status associated with this patient population.

The aqueous extract of Hibiscus sabdariffa calices modulates the production of monocyte chemoattractant protein-1 in humans.

Diet supplementation and/or modulation is an important strategy to significantly improve human health. The search of plants as additional sources of bioactive phenolic compounds is relevant in this context. The aqueous extract of Hibiscus sabdariffa is rich in anthocyanins and other phenolic compounds including hydroxycitric and chlorogenic acids. Using this extract we have shown an effective protection of cultured peripheral blood mononuclear cells from the cellular death induced by H(2)O(2) and a significant role in the production of inflammatory cytokines. In vitro, the extract promotes the production of IL-6 and IL-8 and decreases the concentration of MCP-1 in supernatants in a dose-dependent manner. In humans, the ingestion of an acute dose of the extract (10g) was well tolerated and decreased plasma MCP-1 concentrations significantly without further effects on other cytokines. This effect was not due to a concomitant increase in the antioxidant capacity of plasma. Instead, its mechanisms probably involve a direct inhibition of inflammatory and/or metabolic pathways responsible for MCP-1 production, and may be relevant in inflammatory and chronic conditions in which the role of MCP-1 is well established. If beneficial effects are confirmed in patients, Hibiscus sabdariffa could be considered a valuable traditional herbal medicine for the treatment of chronic inflammatory diseases with the advantage of being devoid of caloric value or potential alcohol toxicity.

Pitfalls in measuring high-density lipoprotein cholesterol concentrations in HIV-infected patients.

OBJECTIVES: HIV infection and its treatment are associated with dyslipidaemia and increased risk of cardiovascular disease. Accurate high-density lipoprotein (HDL) cholesterol values are necessary for the management of these abnormalities, but current methods have not been properly assessed in these patients. The aim of this study was to assess in HIV-infected patients the consistency and accuracy of a synthetic polymer/detergent homogeneous assay used to measure HDL cholesterol concentrations and to evaluate the impact of storage. METHODS: HDL cholesterol was measured using a synthetic polymer/detergent homogeneous method in samples from HIV-infected patients and healthy subjects for each of the storage regimens: baseline, after 1 week at 4 degrees C, and after 12 months at -80 degrees C. The ultracentrifugation and precipitation assays were used for comparison. RESULTS: Three out of every 20 samples from HIV-infected patients had discrepant HDL cholesterol values with respect to the ultracentrifugation method. Overestimation was associated with high C-reactive protein concentrations and underestimation with plasma gamma-globulin concentrations, an effect that was amplified by any of the storage conditions tested. CONCLUSIONS: Caution is needed when using the synthetic polymer/detergent homogeneous method for direct measurement of HDL cholesterol concentrations in HIV-infected patients. This assay is of limited use in clinical trials in which frozen samples are analysed.