The clinical impact of MTHFR polymorphism on the vascular complications of sickle cell disease

Sickle cell disease (SCD) is one of the most common inherited diseases in the world and the patients present notorious clinical heterogeneity. It is known that patients with SCD present activation of the blood coagulation and fibrinolytic systems, especially during vaso-occlusive crises, but also during the steady state of the disease. We determined if the presence of the factor V gene G1691A mutation (factor V Leiden), the prothrombin gene G20210A variant, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may be risk factors for vascular complications in individuals with SCD. We studied 53 patients with SCD (60% being women), 29 with SS (sickle cell anemia; 28 years, range: 13-52 years) and 24 with SC (sickle-hemoglobin C disease; 38.5 years, range: 17-72 years) hemoglobinopathy. Factor V Leiden, MTHFR C677T polymorphism, and prothrombin G20210A variant were identified by PCR followed by further digestion of the PCR product with specific endonucleases. The following vascular complications were recorded: stroke, retinopathy, acute thoracic syndrome, and X-ray-documented avascular necrosis. Only one patient was heterozygous for factor V Leiden (1.8%) and there was no prothrombin G20210A variant. MTHFR 677TT polymorphism was detected in 1 patient (1.8%) and the heterozygous form 677TC was observed in 18 patients (34%, 9 with SS and 9 with SC disease), a prevalence similar to that reported by others. No association was detected between the presence of the MTHFR 677T allele and other genetic modulation factors, such as alpha-thalassemia, ß-globin gene haplotype and fetal hemoglobin. The presence of the MTHFR 677T allele was associated with the occurrence of vascular complications in SCD, although this association was not significant when each complication was considered separately. In conclusion, MTHFR C677T polymorphism might be a risk factor for vascular complications in SCD.Universidade Federal de São Paulo (UNIFESP) Paulista de Medicina Disciplina de Hematologia e HemoterapiaUNIFESP, Paulista de Medicina Disciplina de Hematologia e HemoterapiaSciEL

Facile synthesis of oxo-/thioxopyrimidines and tetrazoles C–C linked to sugars as novel non-toxic antioxidant acetylcholinesterase inhibitors

Microwave-assisted synthesis of oxo-/thioxopyrimidines and tetrazoles linked to furanoses with D-xylo and D-ribo configuration, and to a D-galacto pyranose is reported and compared to conventional methods. Reaction of dialdofuranoses and dialdopyranoses with a b-keto ester and urea or thiourea under micro wave irradiation at 300 W gave in 10 min the target molecules containing the 2-oxo- or 2-thioxo-pyrimidine ring in high yield. The tetrazole-derived compounds were obtained in two steps by reaction of the formyl group with hydroxylamine hydrochloride, copper sulfate, triethylamine and dicyclohexylcarbodiimide to give an intermediate nitrile, which was then treated with sodium azide. The use of microwave irradiation in the latter step also resulted in a considerably shorter reaction time (10 min) compared to hours under conventional heating to obtain a complete starting materials conversion. Acetylcholinesterase inhibition ranged from 20% to 80% for compounds concentration of 100 lg/mL, demonstrating the potential of this family of compounds for the control of Alzheimer’s disease symptoms. Most of the compounds showed antioxidant activity in the b-carotene/linoleic acid assay, some of them exhibiting IC50 values in the same order of magnitude as those of gallic acid. The bioactive compounds did not show cytotoxic effects to human lymphocytes using the MTT method adapted for non-adherent cells, nor geno toxicity determined by the short-term in vitro chromosomal aberration assay.info:eu-repo/semantics/publishedVersio

Performance And Economic Analysis Of Finished Lambs In Feedlot

This study aimed to evaluate animal performance and economic performance of feedlot crossbred lambs (Santa Inês+ - Suffolk) fed different diets based on hay from Cynodon dactylon genotypes, through the use of financial measures considering only the period of feedlot, without relating it to the complete management cycle. A total of 30 intact crossbred Suffolk lambs, identified with earrings, with an average age of 90 days and an average body weight of 21.5 kg were used in this study. Diets were formulated using as treatments a standard concentrate and hay of the Cynodon dactylon genotypes Jiggs, Vaquero, Tifton 68, Coast-Cross, Tifton 85 and Russell in a 60:40 forage-to-concentrate ratio. The treatments were distributed in a randomized complete block design with five replicates. There were significant differences between diets in terms of total expenditure on food, and the highest values were obtained for the Jiggs genotype (BRL 48.96/animal). The animals fed diets based on Tifton 68 hay had a higher rate of return (2.16%) and profitability (34.63%) compared to the other diets. The use of diets based on Tifton 68 hay for feedlot lambs in the finishing phase brings higher economic returns compared to the remaining diets.37129330

Education plays a greater role than age in cognitive test performance among participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Background: Brazil has gone through fast demographic, epidemiologic and nutritional transitions and, despite recent improvements in wealth distribution, continues to present a high level of social and economic inequality. The ELSA-Brasil, a cohort study, aimed at investigating cardiovascular diseases and diabetes, offers a great opportunity to assess cognitive decline in this aging population through time-sequential analyses drawn from the same battery of tests over time. The purpose of this study is to analyze the influence of sex, age and education on cognitive tests performance of the participants at baseline. Methods: Analyses pertain to 14,594 participants with aged 35 to 74 years, who were functionally independent and had no history of stroke or use of neuroleptics, anticonvulsants, cholinesterase inhibitors or antiparkinsonian agents. Mean age was 52.0 ± 9.0 years and 54.2 % of participants were women. Cognitive tests included the word memory tests (retention, recall and recognition), verbal fluency tests (VFT, animals and letter F) and Trail Making Test B. Multivariable linear regression analysis was used to determine the influence of sociodemographic characteristics on the distribution of the final score of each test. Results: Women had significant and slightly higher scores than men in all memory tests and VFT, but took more time to perform Trail B. Reduced performance in all tests was seen with an increase age and, more importantly, with decrease level of education. The word list and VFT scores decreased at about one word for every 10 years of age whereas higher-educated participants scored four words more on the word list test, and six or seven more correct words on VFT, when compared to lower-educated participants. Additionally, the oldest and less educated participants showed significant lower response rates in all tests. Conclusions: The higher influence of education than age in this Brazilian population reinforce the need for caution in analyzing and diagnosing cognitive impairments based on traditional cognitive tests and the importance of searching for education-free cognitive tests, especially in low and middle-income countries

Análisis del efecto de materiales de cambio de fase sobre la demanda de calefacción en una casa fotovoltaica

CIES2020 - XVII Congresso Ibérico e XIII Congresso Ibero-americano de Energia SolarRESUMEN: Este trabajo evalúa el efecto que tiene la integración de materiales de cambio de fase (MCF) en la envolvente de los edificios, sobre la operación de un sistema de generación solar fotovoltaica acoplado con bomba de calor para cubrir las necesidades térmicas de dicho edificio. A partir de una instalación a escala real, se han realizado modelos en EnergyPlus de diferentes escenarios de estudio intermedios, teniendo en cuenta que la aplicación de los MCF microencapsulados como revestimiento de paredes interiores, requiere de un material de sustrato y un mortero para que se incorpore, evaluando de esta forma el efecto que tiene cada uno de los elementos. Se ha simulado y evaluado el efecto en cada escenario de estudio sobre la demanda energética del demostrador, desde la solución constructiva del fabricante hasta la solución con el mortero aditivado con MCF aplicado como recubrimiento interior de las paredes. En paralelo se ha realizado la simulación mediante TRNSYS de una instalación fotovoltaica de 50, 100, 200 y 300 W conectadas a una bomba de calor sobre la que se ha considerado que tiene un rendimiento en calefacción de 3 y un rendimiento de refrigeración de 2. Los resultados muestran que hay una gran cantidad de energía de calefacción que se pierde en los momentos en los que la demanda de calefacción es reducida y la disponibilidad de energía solar es alta. También se ha podido comprobar que el dimensionado para refrigeración es más crítico que para calefacción. Finalmente cabe indicar que el presente trabajo se ha realizado dentro del marco del proyecto SUDOKET financiado por la convocatoria Interreg SUDOE.ABSTRACT: The present work evaluates the effect that the incorporation of Phase Change Materials (PCM) in the building envelope has in the operation of a solar photovoltaic (PV) generation system coupled with a heat pump for covering the thermal demand of a building. Based on data from a real scale facility, the EnergyPlus models of different case scenarios have been performed, taking into account that the application of microencapsulated PCM as an interior wall coating requires a substrate material and a mortar matrix to be embedded into. The effect on each case scenario on the buildings energy demand, from the manufacturer constructive walls solution until the PCM enhanced mortar applied as the interior wall coating, has been simulated and evaluated. In parallel, the TRNSYS simulation of a solar photovoltaic (PV) system has been performed, considering 50, 100, 200 and 300 W connected to a heat pump with a heating performance of 3 and a cooling performance of 2. The obtained results show that there is a large amount of heating energy that is wasted when the demand for heating is low and the availability of solar energy is high. It has also been demonstrated that sizing for cooling is more critical than for heating. Finally, it should be indicated that this work has been carried out within the SUDOKET project financed by the Interreg SUDOE programme.info:eu-repo/semantics/publishedVersio

The origin of fracture in the I-ECAP of AZ31B magnesium alloy

Magnesium alloys are very promising materials for weight-saving structural applications due to their low density, comparing to other metals and alloys currently used. However, they usually suffer from a limited formability at room temperature and low strength. In order to overcome those issues, processes of severe plastic deformation (SPD) can be utilized to improve mechanical properties, but processing parameters need to be selected with care to avoid fracture, very often observed for those alloys during forming. In the current work, the AZ31B magnesium alloy was subjected to SPD by incremental equal-channel angular pressing (I-ECAP) at temperatures varying from 398 K to 525 K (125 °C to 250 °C) to determine the window of allowable processing parameters. The effects of initial grain size and billet rotation scheme on the occurrence of fracture during I-ECAP were investigated. The initial grain size ranged from 1.5 to 40 µm and the I-ECAP routes tested were A, BC, and C. Microstructures of the processed billets were characterized before and after I-ECAP. It was found that a fine-grained and homogenous microstructure was required to avoid fracture at low temperatures. Strain localization arising from a stress relaxation within recrystallized regions, namely twins and fine-grained zones, was shown to be responsible for the generation of microcracks. Based on the I-ECAP experiments and available literature data for ECAP, a power law between the initial grain size and processing conditions, described by a Zener–Hollomon parameter, has been proposed. Finally, processing by various routes at 473 K (200 °C) revealed that route A was less prone to fracture than routes BC and C

Metabolic and nutritional triggers associated with increased risk of liver complications in SARS-CoV-2

Obesity, diabetes, cardiovascular and respiratory diseases, cancer and smoking are risk factors for negative outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can quickly induce severe respiratory failure in 5% of cases. Coronavirus disease-associated liver injury may occur during progression of SARS-CoV-2 in patients with or without pre-existing liver disease, and damage to the liver parenchyma can be caused by infection of hepatocytes. Cirrhosis patients may be particularly vulnerable to SARS-CoV-2 if suffering with cirrhosis-associated immune dysfunction. Furthermore, pharmacotherapies including macrolide or quinolone antibiotics and steroids can also induce liver damage. In this review we addressed nutritional status and nutritional interventions in severe SARS-CoV-2 liver patients. As guidelines for SARS-CoV-2 in intensive care (IC) specifically are not yet available, strategies for management of sepsis and SARS are suggested in SARS-CoV-2. Early enteral nutrition (EN) should be started soon after IC admission, preferably employing iso-osmolar polymeric formula with initial protein content at 0.8 g/kg per day progressively increasing up to 1.3 g/kg per day and enriched with fish oil at 0.1 g/kg per day to 0.2 g/kg per day. Monitoring is necessary to identify signs of intolerance, hemodynamic instability and metabolic disorders, and transition to parenteral nutrition should not be delayed when energy and protein targets cannot be met via EN. Nutrients including vitamins A, C, D, E, B6, B12, folic acid, zinc, selenium and ω-3 fatty acids have in isolation or in combination shown beneficial effects upon immune function and inflammation modulation. Cautious and monitored supplementation up to upper limits may be beneficial in management strategies for SARS-CoV-2 liver patients

Incremental proximal methods for large scale convex optimization

Laboratory for Information and Decision Systems Report LIDS-P-2847We consider the minimization of a sum∑m [over]i=1 fi (x) consisting of a large number of convex component functions fi . For this problem, incremental methods consisting of gradient or subgradient iterations applied to single components have proved very effective. We propose new incremental methods, consisting of proximal iterations applied to single components, as well as combinations of gradient, subgradient, and proximal iterations. We provide a convergence and rate of convergence analysis of a variety of such methods, including some that involve randomization in the selection of components.We also discuss applications in a few contexts, including signal processing and inference/machine learning.United States. Air Force Office of Scientific Research (grant FA9550-10-1-0412

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters