Social Resilience : Earthquake Consequences to an Intense

Disclosed generally the impact they have caused to the life of society intense seismic activity in the area, especially the tectonic situation of Ecuador and particularized on stage at the coastal territory, given its proximity to the Ring of Fire. a balance of the most intense earthquakes occurred during the twentieth century and at the time of this century and is particularized in the consequences resulting therefrom for society is shown. An analysis related to the vision deployed by the UN related to resilience as a capacity to prevent disasters and crises are addressed, as well as to foresee natural disasters, minimize them, take them into account or recover from them on time and in an efficient and sustainable including protection. The results of an assessment of the resilience evacuees at Camp “Los Tamarindos” Portoviejo city where the SV-RES scale methodology that evaluates twelve dimensions developed offered

Successful Implementation of a Perioperative Glycemic Control Protocol in Cardiac Surgery: Barrier Analysis and Intervention Using Lean Six Sigma

Although the evidence strongly supports perioperative glycemic control among cardiac surgical patients, there is scant literature to describe the practical application of such a protocol in the complex ICU environment. This paper describes the use of the Lean Six Sigma methodology to implement a perioperative insulin protocol in a cardiac surgical intensive care unit (CSICU) in a large academic hospital. A preintervention chart audit revealed that fewer than 10% of patients were admitted to the CSICU with glucose <200 mg/dL, prompting the initiation of the quality improvement project. Following protocol implementation, more than 90% of patients were admitted with a glucose <200 mg/dL. Key elements to success include barrier analysis and intervention, provider education, and broadening the project scope to address the intraoperative period

Activation-induced cytidine deaminase localizes to G-quadruplex motifs at mutation hotspots in lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a molecularly heterogeneous group of malignancies with frequent genetic abnormalities. G-quadruplex (G4) DNA structures may facilitate this genomic instability through association with activation-induced cytidine deaminase (AID), an antibody diversification enzyme implicated in mutation of oncogenes in B-cell lymphomas. Chromatin immunoprecipitation sequencing analyses in this study revealed that AID hotspots in both activated B cells and lymphoma cells in vitro were highly enriched for G4 elements. A representative set of these targeted sequences was validated for characteristic, stable G4 structure formation including previously unknown G4s in lymphoma-associated genes, CBFA2T3, SPIB, BCL6, HLA-DRB5 and MEF2C, along with the established BCL2 and MYC structures. Frequent genome-wide G4 formation was also detected for the first time in DLBCL patient-derived tissues using BG4, a structure-specific G4 antibody. Tumors with greater staining were more likely to have concurrent BCL2 and MYC oncogene amplification and BCL2 mutations. Ninety-seven percent of the BCL2 mutations occurred within G4 sites that overlapped with AID binding. G4 localization at sites of mutation, and within aggressive DLBCL tumors harboring amplified BCL2 and MYC, supports a role for G4 structures in events that lead to a loss of genomic integrity, a critical step in B-cell lymphomagenesis

Simultaneous deletion of Tet1 and Tet3 increases transcriptome variability in early embryogenesis

Dioxygenases of the TET (Ten-Eleven Translocation) family produce oxidized methylcytosines, intermediates in DNA demethylation, as well as new epigenetic marks. Here we show data suggesting that TET proteins maintain the consistency of gene transcription. Embryos lacking Tet1 and Tet3 (Tet1/3 DKO) displayed a strong loss of 5-hydroxymethylcytosine (5hmC) and a concurrent increase in 5-methylcytosine (5mC) at the eight-cell stage. Single cells from eight-cell embryos and individual embryonic day 3.5 blastocysts showed unexpectedly variable gene expression compared with controls, and this variability correlated in blastocysts with variably increased 5mC/5hmC in gene bodies and repetitive elements. Despite the variability, genes encoding regulators of cholesterol biosynthesis were reproducibly down-regulated in Tet1/3 DKO blastocysts, resulting in a characteristic phenotype of holoprosencephaly in the few embryos that survived to later stages. Thus, TET enzymes and DNA cytosine modifications could directly or indirectly modulate transcriptional noise, resulting in the selective susceptibility of certain intracellular pathways to regulation by TET proteins.J.K. was supported by a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Research. W.A.P. was supported by the National Science Foundation predoctoral graduate research fellowship while this work was being performed, and subsequently by a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Research. L.C. was the recipient of a Feodor-Lynen fellowship from the Alexander von Humboldt foundation. M.L. is supported by the Max Planck Society within its International Max Planck Research School for Computational Biology and Scientific Computing program (IMPRS-CBSC). A.T. was the recipient of an Irvington postdoctoral fellowship from the Cancer Research Institute. This work was supported by NIH R01 Grants AI044432 and HD065812 (to A.R.) and a Director’s New Innovator Award (DP2-OD-008646-01) (to S.K.).This is the author accepted manuscript. The final version is available from The National Academy of Sciences via http://dx.doi.org/10.1073/pnas.151051011

Aging in fragile X syndrome

Many studies have focused on the behavior and cognitive problems in young patients with fragile X syndrome (FXS), but there are no studies about the problems in aging for those with FXS. The discovery of the fragile X-associated tremor ataxia syndrome (FXTAS), a neurodegenerative disorder related to elevated FMR1-mRNA, in elderly men and some women with the premutation, intensified the need for aging studies in FXS. Approximately 40% of males with FXS have repeat size mosaicism and as a result, some of these individuals also have elevated levels of FMR1-mRNA which theoretically puts them at risk for FXTAS. Here, we have surveyed all of the aging patients with FXS that we have followed over the years to clarify the medical complications of aging seen in those with FXS. Data was collected from 62 individuals with the FXS full mutation (44 males; 18 females) who were at least 40 years old at their most recent clinical examination. We found that the five most frequent medical problems in these patients were neurological problems (38.7%), gastrointestinal problems (30.6%), obesity (28.8%), hypertension (24.2%) and heart problems (24.2%). Movement disorders were significantly different between males and females (38.6% vs.10.2%, p = 0.029). We did not find any differences in medical problems between those with a full mutation and those with mosaicism. Identification of medical problems associated with aging in FXS is important to establish appropriate recommendations for medical screening and treatment considerations

Predictive models of insulin resistance derived from simple morphometric and biochemical indices related to obesity and the metabolic syndrome in baboons

<p>Abstract</p> <p>Background</p> <p>Non-human primates are valuable models for the study of insulin resistance and human obesity. In baboons, insulin sensitivity levels can be evaluated directly with the euglycemic clamp and is highly predicted by adiposity, metabolic markers of obesity and impaired glucose metabolism (i.e. percent body fat by DXA and HbA_1c). However, a simple method to screen and identify obese insulin resistant baboons for inclusion in interventional studies is not available.</p> <p>Methods</p> <p>We studied a population of twenty baboons with the euglycemic clamp technique to characterize a population of obese nondiabetic, insulin resistant baboons, and used a multivariate linear regression analysis (adjusted for gender) to test different predictive models of insulin sensitivity (insulin-stimulated glucose uptake = Rd) using abdominal circumference and fasting plasma insulin. Alternatively, we tested in a separate baboon population (n = 159), a simpler model based on body weight and fasting plasma glucose to predict the whole-body insulin sensitivity (Rd/SSPI) derived from the clamp.</p> <p>Results</p> <p>In the first model, abdominal circumference explained 59% of total insulin mediated glucose uptake (Rd). A second model, which included fasting plasma insulin (log transformed) and abdominal circumference, explained 64% of Rd. Finally, the model using body weight and fasting plasma glucose explained 51% of Rd/SSPI. Interestingly, we found that percent body fat was directly correlated with the adipocyte insulin resistance index (r = 0.755, p < 0.0001).</p> <p>Conclusion</p> <p>In baboons, simple morphometric measurements of adiposity/obesity, (i.e. abdominal circumference), plus baseline markers of glucose/lipid metabolism, (i.e. fasting plasma glucose and insulin) provide a feasible method to screen and identify overweight/obese insulin resistant baboons for inclusion in interventional studies aimed to study human obesity, insulin resistance and type 2 diabetes mellitus.</p

Detection of G-quadruplex DNA in mammalian cells

It has been proposed that guanine-rich DNA forms four-stranded structures in vivo called G-quadruplexes or G4 DNA. G4 DNA has been implicated in several biological processes, but tools to study G4 DNA structures in cells are limited. Here we report the development of novel murine monoclonal antibodies specific for different G4 DNA structures. We show that one of these antibodies designated 1H6 exhibits strong nuclear staining in most human and murine cells. Staining intensity increased on treatment of cells with agents that stabilize G4 DNA and, strikingly, cells deficient in FANCJ, a G4 DNA-specific helicase, showed stronger nuclear staining than controls. Our data strongly support the existence of G4 DNA structures in mammalian cells and indicate that the abundance of such structures is increased in the absence of FANCJ. We conclude that monoclonal antibody 1H6 is a valuable tool for further studies on the role of G4 DNA in cell and molecular biology

Cross-Sectional Exploration of Plasma Biomarkers of Alzheimer\u27s Disease in Down Syndrome: Early Data from the Longitudinal Investigation for Enhancing Down Syndrome Research (LIFE-DSR) Study

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ1-40, Aβ1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology