Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly afflicts the elderly population. Soluble oligomers (AβOs) has been implicated in AD ...pathogenesis: however, the molecular events underlying a role for Aβ are not well understood. We studied the effects of AβOs on mitochondrial function and on key proteins that regulate mitochondrial dynamics and biogenesis in hippocampal neurons and PC-12 cells. We find that AβOs treatment caused a reduction in total Mfn1 after a 2 h exposure (42 ± 11%); while DRP1 increased at 1 and 2 h (205 ± 22% and 198 ± 27%, respectively), correlating to changes in mitochondrial morphology. We also observed that SIRT1 levels were reduced after acute and chronic AβOs treatment (68 ± 7% and 77 ± 6%, respectively); while PGC-1α levels were reduced with the same time treatments (68 ± 8% and 67 ± 7%, respectively). Interestingly, we found that chronic treatment with AβOs increased the levels of pSIRT1 (24 h: 157 ± 18%), and we observed changes in the PGC-1α and p-SIRT1 nucleus/cytosol ratio and SIRT1-PGC-1α interaction pattern after chronic exposure to AβOs. Our data suggest that AβOs induce important changes in the level and localization of mitochondrial proteins related with the loss of mitochondrial function that are mediated by a fast and sustained SIRT1/PGC-1α complex disruption promoting a “non-return point” to an irreversible synaptic failure and neuronal network disconnection.
Sentinel lymph node (SLN) biopsy is useful for the prognostic stratification of patients with thick melanoma. Identifying which variables are associated with SLN involvement and establishing risk in ...different subgroups of patients could be useful for guiding the indication of SLN biopsy. The value of complete lymph node dissection (CLND) in patients with a positive SLN biopsy is currently under debate.
To identify factors associated with SLN involvement in thick melanoma we performed a multicentric retrospective cohort study involving 660 patients with thick melanoma who had undergone SLN biopsy. To analyze the role of CLND in thick melanoma patients with a positive SLN biopsy, we built a multivariate Cox proportional hazards model for melanoma-specific survival (MSS) and disease-free survival (DFS) and compared 217 patients who had undergone CLND with 44 who had not.
The logistic regression analysis showed that age, histologic subtype, ulceration, microscopic satellitosis, and lymphovascular invasion were associated with nodal disease. The CHAID (Chi-squared Automatic Interaction Detection) decision tree showed ulceration to be the most important predictor of lymphatic involvement. For nonulcerated melanomas, the histologic subtype lentigo maligna melanoma was associated with a low rate of SLN involvement (4.3%). No significant differences were observed for DFS and MSS between the CLND performed and not-performed groups. Nodal status on CLND was associated with differences in DFS and MSS rates.
We identified subgroups of thick melanoma patients with a low likelihood of SLN involvement. CLND does not offer survival benefit, but provides prognostic information.
In this work the results on the first use of an activated composite membrane (ACM) containing Cyanex 923 for the extraction and transport of phenol are presented. A new dense layer-ACM configuration ...constituted by piperazine showed better stability than that prepared with 1,3-phenylenediamine. The effects of several parameters on the transport of phenol such as feed phase pH, carrier concentration and stripping phase composition were evaluated. The performance of the membrane was also evaluated during continuous additions of phenol and for a long period of time, observing the same rate of extraction and reextraction. Moreover, phenol transport was evaluated starting from synthetic wastewater of resin production plants type. The results exhibit the potential use of ACMs in the elimination and transport of organic species, even when analyte is initially found in complex solutions.
The cardiovascular disease pandemic has promoted the cardiovascular polypill as one of the most scalable public health strategies to improve cardiovascular risk by increasing accessibility and ...adherence to treatments. Data from randomized clinical trials has shown that the polypill strategy significantly improves adherence as well as risk factor control (cholesterol and blood pressure), however, to date, no information from phase IV registries has been available.
We conducted a multicentre, observational and prospective registry of a polypill-based treatment strategy. A total of 1193 patients in Mexico were included. Patient demographics, clinical history, blood pressure, analysis of blood lipids and the Framingham risk score were measured at baseline and after 12 months of treatment with the CNIC-Ferrer polypill.
At one year with the polypill, systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels changed from mean 146.9 mmHg to 128 mmHg (p <0.001), and from 89.1 mmHg to 80.4 mmHg (p <0.001) respectively. LDLc levels were significantly reduced 132.5–107.6 mg/dL (p <0.001). The 10 year Framingham cardiovascular disease risk was also reduced in the high-risk group (33.7 + 22.0 vs. 21.2 + 14.8; p <0.001) and in the intermediate risk group (23.7 + 14.8 vs. 12.7 + 11.4; p <0.001).
To our knowledge, the results of the current study constitute the first real life data on the impact of a polypill therapy on cardiovascular risk factor control. The results show major improvements on the primary outcome, above and beyond those presented previously in the setting of randomized clinical trials.
En este trabajo se determina n l as constantes de acidez del ácido ascórbico ( AA ) por polarimetría, mediante una titulación ácido - base . Los resultados obtenidos por esta técnica se procesaron ...mediante el ajuste de los ángulos de rotación medidos como función del pH, utilizando para el ajuste las leyes de Biot y de aditividad para los ángulos de rotación . Se reali zaron ajustes de partes seleccionadas de la función, tanto por regresión no lineal como por regresión lineal . Los valores más confiables obtenidos son pK a1 = 4.1 49 ± 0.0 22 y pK a2 = 1 1 . 927 ± 0.0 62, por regresión no lineal de los datos a A= 578 nm, con desviaciones estándar de la regresión de 0.046 y 0.075 , re s pectivamente. Estos valores son comparables con los valores reportados con otras técnicas.
National, regional and global scientific production and research capacity for physical activity - PA may contribute to improving public health PA policies and programs. There is an uneven ...distribution of research productivity by region and country income group, where countries with the highest burden of non-communicable diseases attributable to physical inactivity having low research productivity. A first step towards improving global research capacity is to objectively quantify patterns, trends, and gaps in PA research. This study describes national, regional and global trends and patterns of PA research from 1950 to 2019.
A systematic review using searches in PubMed, SCOPUS and ISI Web of Knowledge databases was conducted in August 2017 and updated between January and May 2020. The review was registered at the PROSPERO database number CRD42017070153. PA publications per 100,000 inhabitants per country was the main variable of interest. Descriptive and time-trend analyses were conducted in STATA version 16.0.
The search retrieved 555,468 articles of which 75,756 were duplicates, leaving 479,712 eligible articles. After reviewing inclusion and exclusion criteria, 23,860 were eligible for data extraction. Eighty-one percent of countries (n = 176) had at least one PA publication. The overall worldwide publication rate in the PA field was 0.46 articles per 100,000 inhabitants. Europe had the highest rate (1.44 articles per 100,000 inhabitants) and South East Asia had the lowest (0.04 articles per 100,000 inhabitants). A more than a 50-fold difference in publications per 100,000 inhabitants was identified between high and low-income countries. The least productive and poorest regions have rates resembling previous decades of the most productive and the richest.
This study showed an increasing number of publications over the last 60 years with a growing number of disciplines and research methods over time. However, striking inequities were revealed and the knowledge gap across geographic regions and by country income groups was substantial over time. The need for regular global surveillance of PA research, particularly in countries with the largest data gaps is clear. A focus on the public health impact and global equity of research will be an important contribution to making the world more active.
Visceral leishmaniasis is an opportunistic disease in HIV-1 infected individuals, unrecognized as a determining factor for AIDS diagnosis. The growing geographical overlap of HIV-1 and
infections is ...an emerging challenge worldwide, as co-infection increases morbidity and mortality for both infections. Here, we determined the prevalence of people living with HIV (PWH) with a previous or ongoing infection by
and investigated the virological and immunological factors associated with co-infection. We adopted a two-stage cross-sectional cohort (CSC) design (CSC-I,
= 5,346 and CSC-II,
= 317) of treatment-
HIV-1-infected individuals in Bahia, Brazil. In CSC-I, samples collected between 1998 and 2013 were used for serological screening for leishmaniasis by an in-house Enzyme-Linked Immunosorbent Assay (ELISA) with SLA (Soluble
Antigen), resulting in a prevalence of previous or ongoing infection of 16.27%. Next, 317 PWH were prospectively recruited from July 2014 to December 2015 with the collection of sociodemographic and clinical data. Serological validation by two different immunoassays confirmed a prevalence of 15.46 and 8.20% by anti-SLA, and anti-HSP70 serology, respectively, whereas 4.73% were double-positive (DP). Stratification of these 317 individuals in DP and double-negative (DN) revealed a significant reduction of CD4
counts and CD4
/CD8
ratios and a tendency of increased viral load in the DP group, as compared to DN. No statistical differences in HIV-1 subtype distribution were observed between the two groups. However, we found a significant increase of CXCL10 (
= 0.0076) and a tendency of increased CXCL9 (
= 0.061) in individuals with DP serology, demonstrating intensified immune activation in this group. These findings were corroborated at the transcriptome level in independent Leishmania- and HIV-1-infected cohorts (Swiss HIV Cohort and Piaui Northeast Brazil Cohort), indicating that CXCL10 transcripts are shared by the IFN-dominated immune activation gene signatures of both pathogens and positively correlated to viral load in untreated PWH. This study demonstrated a high prevalence of PWH with
seropositivity in Bahia, Brazil, linked to IFN-mediated immune activation and a significant decrease in CD4
levels. Our results highlight the urgent need to increase awareness and define public health strategies for the management and prevention of HIV-1 and
co-infection.
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