Multiscale characterization of the micromechanics of pure Mg

An important limitation of wrought (rolled and extruded) Mg alloys is their inherent strong mechanical anisotropy, a consequence of their hexagonal closed- packed (hcp) lattice. Several reasons contribute to this effect. First, at room temperature, the critical resolved shear stresses (CRSSs) of basal and non-basal slip systems have very different values, spanning several orders of magnitude; second, twinning, a very common deformation mechanism in these materials, exhibits a pronounced polarity, i.e. its activation is dependent on the relative orientation between the c-axis and the applied stress; finally, both hot and cold deformation processing textures are often quite sharp and the way the activation of different slip systems is influenced by the local texture and grain boundary network is not clear. Together, these factors lead to a dependence of the dominant deformation mechanisms on the texture, grain size, testing mode (tension or compression) and the testing direction, resulting in large differences in yield stress values and strain-hardening responses. In this work, we adopt a multiscale characterization strategy to unravel the micromechanisms of pure Mg. First, we present a coupled experimental and simulation study on the nanoindentation of pure Mg at different temperatures to determine the critical resolved shear stress evolution of the different slip systems at the single crystal level [1-3]. For this, several indentations were performed at temperatures between RT and 300 °C in individual grains of a polycrystalline sheet of pure Mg with different crystallographic orientations. The deformation profile and the microstructure around the indents was analyzed by atomic force microscopy (AFM) and electron backscatter diffraction (EBSD), to determine the CRSS of the different slip systems without grain boundary effects. EBSD assisted trace analysis during in-situ SEM mechanical testing of cold-rolled polycrystalline Mg sheets was then used to account for the role of the local microstructure, such as the local texture and grain boundary network, on the activation of the different deformation modes, In particular, it was found that, with decreasing grain size, at room temperature, a clear transition from non-basal to basal-slip dominated flow takes place under tension [4] and a transition from twinning to basal slip takes place under compression [5]. On the other hand, a similar transition from twinning to basal slip takes place with increasing temperature and decreasing strain rate [6]. The emergence of basal slip as a dominant mechanism is shown to be due to increasing levels of connectivity between favorably oriented grains, which facilitate slip transfer across grain boundaries. This study emphasizes the complexity of the micromechanics of pure Mg, where the activation of different deformation modes is strongly affected, not only by their single crystal CRSS levels, but also by the local grain boundary networks and local texture emerging from processing

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Síndrome de distres respiratorio agudo

Acute Respiratory Distress Syndrome (ARDS) is a condition that does not allow normal breathing, limiting oxygenation in the blood, and preventing the proper development of body functions at levels that compromise vital signs that can lead to death if it is not treated in time. This respiratory condition can be further complicated if it interacts with other risk factors or chronic diseases presented by the patient. The treatment, once the acute respiratory deficiency has been determined, is used at the discretion of the specialist doctor based on knowledge of the indicated pathology. Being the most used, phar-macological treatments for the reversal of bronchoconstriction, vasoconstriction, coagulation disorders and inflammatory processes that damage lung tissue. Another option to treat this pathology is ventilation with oscillation with high frequency, which uses a special respirator that allows to improve oxygenation. The general focus of this work is to present the main causes, symptoms and treatments for this pathology. The results were obtained through the development of a bibliographic research, limited to a review methodology, which allows us to conclude that even though much progress has been made in medical studies and with the current clinical technological advances, there is no validated measurement for stratify patients' risk of developing the syndrome, which has raised countless alerts regarding clinical procedures to continue to understand their pathophysiology well and definition to effectively initiate and direct the treatments to be applied, placing greater emphasis on the prevention of this disease.El Síndrome de Distrés Respiratorio Agudo (SDRA) es una condición que no permite una respiración normal, limitando la oxigenación en la sangre, y evitando el buen desenvolvimiento de las funciones del cuerpo en niveles comprometedores de los signos vitales que pueden llevar a la muerte si no es tratado a tiempo. Esta afección respiratoria puede complicarse en mayor manera si este interactúa con otros factores de riesgo o enfermedades crónicas presentadas por el paciente. El tratamiento, una vez determinada la deficiencia respiratoria aguda se emplea a criterio del médico especialista en base a los conocimientos sobre la patología indicada. Siendo los más utilizados, los tratamientos farmacológicos para la reversión de la broncoconstricción, la vasoconstricción, las alteraciones de la coagulación y los procesos inflamatorios que lesionan el tejido pulmonar. Otra opción para tratar esta patología es la ventilación mediante oscilación con frecuencia elevada, la cual utiliza un respirador especial que permite mejorar la oxigenación. El enfoque general del presente trabajo es dar a conocer las principales causas, síntomas y tratamientos para esta patología. Los resultados se obtuvieron mediante el desarrollo de una investigación de tipo bibliográfica, delimitada a una metodología de revisión, que permite concluir que aun y cuando se ha avanzado mucho en estudios médicos y con los avances tecnológicos clínicos de la actualidad no hay una medición validada para estratificar el riesgo de los pacientes de desarrollar el síndrome, lo que ha levantado innumerables alertas en cuanto a los procedimientos clínicos a seguir entendiendo bien su fisiopatología y definición para iniciar y dirigir efectivamente los tratamientos a aplicar, haciendo mayor énfasis en la prevención de esta enfermedad

Microstructure, Mechanical Properties and Creep of Magnesium Alloy Elektron21 Reinforced with AlN Nanoparticles by Ultrasound-Assisted Stirring

International audienc