Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis

Multifactorial mechanisms underlying late-onset Alzheimer’s disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system’s integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions

Impact of Lipodystrophy on the prevalence and components of metabolic syndrome in HIV-infected patients

Background: In HIV-infected patients, combination antiretroviral therapy (cART) is associated with clinical lipodystrophy (CL) and metabolic abnormalities (MA). This study aimed to evaluate the prevalence of the metabolic syndrome (MS) and its components, and to determine whether patients with or without CL had a different prevalence of MA.Methods: We evaluated 345 HIV-infected patients on cART using two different MS definitions (NCEP-ATPIII-2005 and IDF-2005) and the Framingham risk score.Results: CL was present in 58.7% of the patients. The prevalence of the MS was 52.2% (ATPIII) and 43.2% (IDF), and it was not significantly different between patients with (W) or without (WT) CL, regardless of the definition used (ATPIII WCL 52.9% vs WT CL 51.1%; p = 0.738; IDF WCL 41.3% vs WTCL 46.0%; p = 0.379). Moderate concordance was observed between the 2 definitions (kappa = 0.484; p < 0.001) and after gender stratification there was good concordance in women (kappa = 0.759; p < 0.001). Patients with CL had lower waist circumference and HDL-C and higher triglycerides levels. In women, CL was significantly associated with MS, hypertriglyceridemia and low HDL cholesterol independently of age, cART and BMI. Patients with CL had a significantly higher risk of coronary heart disease at 10 years, measured by the Framingham risk score, than patients without CL. Those with CL and with MS had higher frequencies of moderate and high risk categories than those without MS.Conclusions: The prevalence of the MS was high in these HIV-infected patients with an age average of 40 years and this finding could explain why HIV patients have an increased risk for cardiovascular disease (CVD). © 2011 Freitas et al; licensee BioMed Central Ltd

Central/peripheral fat mass ratio is associated with increased risk of hypertension in hiv-infected patients

The data on the risk of hypertension in human immunodeficiency virus (HIV)-infected patients, particularly in those with lipodystrophy, are controversial. The authors assessed the impact of lipodystrophy on hypertension in a cohort of HIV-infected adults receiving combination antiretroviral therapy. This was a cross-sectional study in which lipodystrophy (clinically and fat mass ratio [FMR]-defined), blood pressure, and body composition (dual-energy x-ray absorptiometry and computed tomography) were evaluated in 368 HIV adults. The prevalence of hypertension in HIV patients with or without clinically or FMR-defined lipodystrophy was similar (with clinical lipodystrophy 35.3% vs without 32.9%, not significant; with FMR lipodystrophy 41.7% vs without 32.2%, not significant). When HIV-infected patients were classified into 4 categories of fat distribution (based on the presence or absence of lipoatrophy and abdominal prominence), isolated lipoatrophy was not significantly associated with hypertension, but patients with isolated central fat accumulation and mixed forms of lipodystrophy had a significantly higher prevalence of hypertension. Hypertensive HIV patients had significantly higher total fat, central, and central/peripheral fat mass ratio than normotensive ones. After adjustment for age, sex, smoking, and body mass index, hypertension remains significantly associated with central/peripheral fat mass ratio (odds ratio, 1.258; 95% confidence interval, 1.008-1.569). Hypertension was not more prevalent in lipodystrophic HIV-infected patients, but was significantly associated with central/peripheral fat mass ratio. © 2012 Wiley Periodicals, Inc

Lipodystrophy defined by Fat Mass Ratio in HIV-infected patients is associated with a high prevalence of glucose disturbances and insulin resistance

Introduction: Combined antiretroviral therapy (cART) in the treatment of HIV-1 infection has been associated with complications, including lipodystrophy, hyperlipidaemia, insulin resistance (IR) and diabetes.Aims: To compare the prevalence of glucose homeostasis disturbances and IR in HIV patients on cART according to the presence of lipodystrophy (defined clinically and by Fat Mass Ratio) and different patterns of fat distribution and to establish their associations.Design: Cross-sectional cohort study.Methods: We evaluated body composition and IR and insulin sensitivity indexes in 345 HIV-infected adults.Results: Patients with clinical lipodystrophy (CL) had higher plasma glucose levels than patients without CL, without significant differences in plasma insulin levels, A1c, HOMA-IR, HOMA-B, QUICKI, or MATSUDA index. Patients with lipodystrophy defined by FMR had higher plasma glucose and insulin levels, A1c, HOMA-IR, QUICKI and MATSUDA than patients without lipodystrophy, without differences in HOMA-B. Higher insulin resistance (HOMA-IR ≥ 4) was present in patients with FMR-defined lipodystrophy. Patients with FMR-defined lipodystrophy had a higher prevalence of IFG, IGT and DM than patients without lipodystrophy. Significant associations between HOMA-IR and total, central and central/peripheral fat evaluated by CT at abdominal level were found and no association between HOMA-IR and peripheral fat. Association between HOMA-IR and total and trunk fat but no association with leg and arm fat (evaluated by DXA) was found.Conclusions: IR and glucose disturbances were significantly increased in patients with FMR-defined lipodystrophy. FMR lipodystrophy definition seems to be a more sensitive determinant of insulin resistance and glucose disturbances than clinical definition. © 2012 Freitas et al.; licensee BioMed Central Ltd.Research Fellowship Dr. Manuel Almeida Ruas, Portuguese Society of Diabetology. Research Fellowship of the Portuguese Association for Clinical Study of AIDS. Research Grant to support doctoral studies in the area of HIV/ AIDS, GlaxoSmithKline Foundation of Health Sciences

Four distinct trajectories of tau deposition identified in Alzheimer's disease

Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging

The effect of acute exercise on cognitive performance in children with and without ADHD

AbstractBackgroundAttention deficit hyperactivity disorder (ADHD) is a common childhood disorder that affects approximately 11% of children in the United States. Research supports that a single session of exercise benefits cognitive performance by children, and a limited number of studies have demonstrated that these effects can also be realized by children with ADHD. The purpose of this study was to examine the effect of acute exercise on cognitive performance by children with and without ADHD.MethodsChildren with and without ADHD were asked to perform cognitive tasks on 2 days following treatment conditions that were assigned in a random, counterbalanced order. The treatment conditions consisted of a 30-min control condition on 1 day and a moderate intensity exercise condition on the other day.ResultsExercise significantly benefited performance on all three conditions of the Stroop Task, but did not significantly affect performance on the Tower of London or the Trail Making Test.Conclusionchildren with and without ADHD realize benefits in speed of processing and inhibitory control in response to a session of acute exercise, but do not experience benefits in planning or set shifting

miRNA in situ hybridization in circulating tumor cells - MishCTC

irculating tumor cells (CTCs) must be phenotypically and genetically characterized before they can be utilized in clinical applications. Here, we present the first protocol for the detection of miRNAs in CTCs using in situ hybridization (ISH) combined with immunomagnetic selection based on cytokeratin (CK) expression and immunocytochemistry. Locked-Nucleic Acid (LNA) probes associated with an enzyme-labeled fluorescence (ELF) signal amplification approach were used to detect miRNA-21 in CTCs. This protocol was optimized using both epithelial tumor (MDA-MB468) and epithelial non-tumor (MCF-10A) cell lines, and miRNA-21 was selected as the target miRNA because of its known role as an onco-miRNA. Hematopoietic cells do not express miRNA-21; thus, miRNA-21 is an ideal marker for detecting CTCs. Peripheral blood samples were taken from 25 cancer patients and these samples were analyzed using our developed protocol. Of the 25 samples, 11 contained CTCs. For all 11 CTC-positive samples, the isolated CTCs expressed both CK and miRNA-21. Finally, the protocol was applied to monitor miRNA-21 expression in epithelial to mesenchymal transition (EMT)-induced MCF-7 cells, an epithelial tumor cell line. CK expression was lost in these cells, whereas miRNA-21 was still expressed, suggesting that miRNA-21 might be a good marker for detecting CTCs with an EMT phenotype.JJDM thanks the Spanish Ministerio de Economía y Competitividad for a Ramón y Cajal Fellowship (Grant CTQ2012-34778). This research was partially supported by Marie Curie Career Integration Grants within the 7th European Community Framework Program (FP7-PEOPLE-2011-CIG-Project Number 294142 to RMSM and FP7-PEOPLE-2012-CIG-Project Number 322276 toJJDM). Thisresearch wasalso partially supported by Consejeria de Salud de la Junta de Andalucı ́ a (PI0294-2012)

Time-resolved thermal lens measurements of the thermo-optical properties of glasses at low temperature down to 20 K

In this work the time resolved thermal lens spectrometry was applied to measure the absolute values of the thermo-optical properties of low silica calcium aluminosilicate and soda lime glasses at low temperatures, in the range between 20 and 300 K. The thermal relaxation calorimetry was used as a complementary technique to determine the specific heat. The results showed a marked decrease of the thermal diffusivity with the temperature rise, with a dependence similar to that of the mean free path (similar to T-1) in the interval between 20 and 70 K, while in the range between 70 and 300 K the dependence was T-(0.33 +/- 0.02). The marked variation of the temperature coefficient of the optical path length change with the temperature rise was attributed to the increase in the coefficient of the electronic polarizability. The results also showed that for the aluminosilicate glass the excess in the specific heat correlated to the so-called boson peak occurred at about 17 K, higher than that of soda lime, which occurs at about 12 K. In conclusion, our results showed the ability of the time resolved thermal lens to determine the thermo-optical properties of glasses at low temperatures, bringing possibilities for experiments in a wide range of optical materials.712

The evolution of diabetic chronic complications after pancreas transplantation

Pancreas transplantation is an invasive procedure that can restore and maintain normoglycemic level very successfully and for a prolonged period in DM1 patients. The procedure elevates the morbimortality rates in the first few months following the surgery if compared to kidney transplants with living donors, but it offers a better quality of life to patients