Erectile dysfunction and quality of life in type 2 diabetic patients: a serious problem too often overlooked.

OBJECTIVE—Within the context of a large, nationwide outcomes research program in type 2 diabetes, we assess the prevalence of self-reported erectile dysfunction and evaluate its impact on quality of life. RESEARCH DESIGN AND METHODS—The study involved 1,460 patients enrolled by 114 diabetes outpatient clinics and 112 general practitioners. Patients were asked to complete a questionnaire investigating their ability to achieve and maintain an erection. Various aspects of quality of life were also assessed depressive using the following instruments: SF-36 Health Survey, diabetes health distress, psychological adaptation to diabetes, depressive symptoms (CES-D scale), and quality of sexual life. RESULTS—Overall, 34% of the patients reported frequent erectile problems, 24% reported occasional problems, and 42% reported no erectile problems. After adjusting for patient characteristics, erectile dysfunction was associated with higher levels of diabetes-specific health distress and worse psychological adaptation to diabetes, which were, in turn, related to worse metabolic control. Erectile problems were also associated with a dramatic increase in the prevalence of severe depressive symptoms, lower scores in the mental components of the SF-36, and a less satisfactory sexual life. A total of 63% of the patients reported that their physicians had never investigated their sexual problems. CONCLUSIONS—Erectile dysfunction is extremely common among type 2 diabetic patients and is associated with poorer quality of life, as measured with generic and diabetes-specific instruments. Despite their relevance, sexual problems are seldom investigated by general practitioners and specialists

Quality of Care and Outcomes in Type 2 Diabetic Patients A comparison between general practice and diabetes clinics

OBJECTIVE—The role of general practice and diabetes clinics in the management of diabetes is still a matter of debate. Methodological flaws in previous studies may have led to inaccurate conclusions when comparing the care provided in these different settings. We compared the care provided to type 2 diabetic patients attending diabetes outpatient clinics (DOCs) or being treated by a general practitioner (GP) using appropriate statistical methods to adjust for patient case mix and physician-level clustering. RESEARCH DESIGN AND METHODS—We prospectively evaluated the process and intermediate outcome measures over 2 years in a sample of 3,437 patients recruited by 212 physicians with different specialties practicing in 125 DOCs and 103 general practice offices. Process measures included frequency of HbA1c, lipids, microalbuminuria, and serum creatinine measurements and frequency of foot and eye examinations. Outcome measures included HbA1c, blood pressure, and total and LDL cholesterol levels. RESULTS—Differences for most process measures were statistically significantly in favor of DOCs. The differences were more marked for patients who were always treated by the same physician within a DOC and if that physician had a specialty in diabetology. Less consistent differences in process measures were detected when patients followed by GPs were compared with those followed by physicians with a specialty other than diabetology. As for the outcomes considered, patients attending DOCs attained better total cholesterol levels, whereas no major differences emerged in terms of metabolic control and blood pressure levels between DOCs and GPs. Physicians' specialties were not independently related to patient outcomes. CONCLUSIONS—Being followed always by the same physician in a DOC, particularly if the physician had a specialty in diabetes, ensured better quality of care in terms of process measures. In the short term, care provided by DOCs was also associated with better intermediate outcome measures, such as total cholesterol levels

Tolerogenic IL-10-engineered dendritic cell-based therapy to restore antigen-specific tolerance in T cell mediated diseases

Tolerogenic dendritic cells play a critical role in promoting antigen-specific tolerance via dampening of T cell responses, induction of pathogenic T cell exhaustion and antigen-specific regulatory T cells. Here we efficiently generate tolerogenic dendritic cells by genetic engineering of monocytes with lentiviral vectors co-encoding for immunodominant antigen-derived peptides and IL-10. These transduced dendritic cells (designated DCIL-10/Ag) secrete IL-10 and efficiently downregulate antigen-specific CD4+ and CD8+ T cell responses from healthy subjects and celiac disease patients in vitro. In addition, DCIL-10/Ag induce antigen-specific CD49b+LAG-3+ T cells, which display the T regulatory type 1 (Tr1) cell gene signature. Administration of DCIL-10/Ag resulted in the induction of antigen-specific Tr1 cells in chimeric transplanted mice and the prevention of type 1 diabetes in pre-clinical disease models. Subsequent transfer of these antigen-specific T cells completely prevented type 1 diabetes development. Collectively these data indicate that DCIL-10/Ag represent a platform to induce stable antigen-specific tolerance to control T-cell mediated diseases

Low P66shc with High SerpinB3 Levels Favors Necroptosis and Better Survival in Hepatocellular Carcinoma.

Cell proliferation and escape from apoptosis are important pathological features of hepatocellular carcinoma (HCC), one of the tumors with the highest mortality rate worldwide. The aim of the study was to evaluate the expression of the pro-apoptotic p66shc and the anti-apoptotic SerpinB3 in HCCs in relation to clinical outcome, cell fate and tumor growth. p66shc and SerpinB3 were evaluated in 67 HCC specimens and the results were correlated with overall survival. Proliferation and cell death markers were analyzed in hepatoma cells overexpressing SerpinB3, under different stress conditions. p66shc-/- mice and xenograft models were also used to assess the effects of p66shc and SerpinB3 on tumor growth. In patients with HCC, the best survival was observed in the subgroup with p66shc levels below median values and SerpinB3 levels above median values. Mice p66shc-/- showed high levels of SerpinB3, while in HepG2 cells overexpressing SerpinB3, p66shc expression was trivial. HepG2 overexpressing SerpinB3 cells were more prone to die after oxidizing treatments, such as diamide or high concentration H2O2. These cells injected in nude mice developed tumors five times smaller than those from control HepG2 cells. Tumors originating from HepG2 overexpressing SerpinB3 cells showed decreased activated Caspase-8, with concomitant increase of RIP3K and decreased levels of cleaved RIP3K, typical features of necroptosis. In conclusion, in patients affected by HCC, the pattern characterized by p66shc downregulation and elevated SerpinB3 levels was associated with markedly better survival. This pattern favored necroptosis in experimental high-stress conditions

Cerium Oxide Nanoparticles Protect Cardiac Progenitor Cells from Oxidative Stress

Cardiac progenitor cells (CPCs) are a promising autologous source of cells for cardiac regenerative medicine. However, CPC culture in vitro requires the presence of microenvironmental conditions (a complex array of bioactive substance concentration, mechanostructural factors, and physicochemical factors) closely mimicking the natural cell surrounding in vivo, including the capability to uphold reactive oxygen species (ROS) within physiological levels in vitro. Cerium oxide nanoparticles (nanoceria) are redox-active and could represent a potent tool to control the oxidative stress in isolated CPCs. Here, we report that 24 h exposure to 5, 10, and 50 !g/mL of nanoceria did not a!ect cell growth and function in cardiac progenitor cells, while being able to protect CPCs from H2O2-induced cytotoxicity for at least 7 days, indicating that nanoceria in an e!ective antioxidant. Therefore, these "ndings con"rm the great potential of nanoceria for controlling ROS-induced cell damage

Amyotrophic Lateral Sclerosis Multiprotein Biomarkers in Peripheral Blood Mononuclear Cells

Amyotrophic lateral sclerosis (ALS) is a fatal progressive motor neuron disease, for which there are still no diagnostic/prognostic test and therapy. Specific molecular biomarkers are urgently needed to facilitate clinical studies and speed up the development of effective treatments.We used a two-dimensional difference in gel electrophoresis approach to identify in easily accessible clinical samples, peripheral blood mononuclear cells (PBMC), a panel of protein biomarkers that are closely associated with ALS. Validations and a longitudinal study were performed by immunoassays on a selected number of proteins. The same proteins were also measured in PBMC and spinal cord of a G93A SOD1 transgenic rat model. We identified combinations of protein biomarkers that can distinguish, with high discriminatory power, ALS patients from healthy controls (98%), and from patients with neurological disorders that may resemble ALS (91%), between two levels of disease severity (90%), and a number of translational biomarkers, that link responses between human and animal model. We demonstrated that TDP-43, cyclophilin A and ERp57 associate with disease progression in a longitudinal study. Moreover, the protein profile changes detected in peripheral blood mononuclear cells of ALS patients are suggestive of possible intracellular pathogenic mechanisms such as endoplasmic reticulum stress, nitrative stress, disturbances in redox regulation and RNA processing.Our results indicate that PBMC multiprotein biomarkers could contribute to determine amyotrophic lateral sclerosis diagnosis, differential diagnosis, disease severity and progression, and may help to elucidate pathogenic mechanisms

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Search for supersymmetry in events with one lepton and multiple jets in proton-proton collisions at root s=13 TeV

Peer reviewe