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Sodium-glucose cotransporter-2 inhibitors protect tissues via cellular and mitochondrial pathways:Experimental and clinical evidence

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World Journal of Experimental Medicine 2024年第2期14卷 46-52页

作者： Raúl Lelio Sanz Sebastián García Menéndez Felipe Inserra Leon Ferder walter Manucha Department of Pathology Facultad de Ciencias MédicasUniversidad Nacional de CuyoMendoza 5500Argentina Department of Pharmacology Instituto de Medicina y Biología Experimental de CuyoCentro Científico TecnológicoMendoza 5500Argentina Department of nephrology Universidad de MaimónidesCiudad Autónoma de Buenos Aires C1405Argentina Department of Cardiology Universidad de MaimónidesCiudad Autónoma de Buenos Aires C1405Argentina

Mitochondrial dysfunction is a key driver of cardiovascular disease(CVD)in metabolic syndrome and *** dysfunction promotes the production of reactive oxygen species(ROS),which cause oxidative stress and *** II,the main mediator of the renin-angiotensin-aldosterone system,also contributes to CVD by promoting ROS *** activity of sirtuins(SIRTs),a family of proteins that regulate cellular metabolism,also worsens oxidative *** of energy production by mitochondria is a common feature of all metabolic *** SIRT levels and 5’adenosine monophosphate-activated protein kinase signaling stimulate hypoxia-inducible factor 1 beta,which promotes ***,in turn,increases autophagy and mitophagy,processes that clear cells of debris and protect against *** cotransporter-2 inhibitors(SGLT2i),a class of drugs used to treat type 2 diabetes,have a beneficial effect on these *** clinical trials have shown that SGLT2i improves cardiac function and reduces the rate of cardiovascular and renal ***2i also increase mitochondrial efficiency,reduce oxidative stress and inflammation,and strengthen *** findings suggest that SGLT2i hold great potential for the treatment of ***,they are proposed as anti-aging drugs;however,rigorous research is needed to validate these preliminary findings.

关键词： Sodium-glucose cotransporter-2 inhibitors Cardiovascular diseases Sirtuins Oxidative stress Inflammation Mitochondrial dysfunction

卒中和短暂性脑缺血发作患者的卒中预防指南美国心脏协会/美国卒中协会为医疗卫生专业人员制定的指南

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国际脑血管病杂志 2014年第11期22卷 805-841页

作者： walter n.kernan Bruce Ovbiagele Henry R.Black Dawn M.Bravata Marc I.Chimowitz Michael D.Ezekowitz Margaret C.Fang Marc Fisher Karen L.Furie 洪道俊黄招君李小兵周美鸿吴成斯王博卢艺吴裕臣代表美国心脏协会卒中委员会、心血管和卒中护理委员会、临床心脏病学委员会以及周围血管病委员会南昌大学第一附属医院神经内科 330006

本更新版指南旨在为缺血性卒中或短暂性脑缺血发作存活者的卒中预防提供全面和及时的循证推荐.本指南适用于所有为上述患者提供二级预防的临床医生.这些循证推荐包括危险因素的控制、血管闭塞的干预、心源性栓塞的抗栓治疗以及非心源性... 详细信息

本更新版指南旨在为缺血性卒中或短暂性脑缺血发作存活者的卒中预防提供全面和及时的循证推荐.本指南适用于所有为上述患者提供二级预防的临床医生.这些循证推荐包括危险因素的控制、血管闭塞的干预、心源性栓塞的抗栓治疗以及非心源性栓塞性卒中的抗血小板治疗.还对各种特殊情况下复发性卒中的预防提供了推荐意见,包括主动脉弓粥样硬化、动脉夹层分离、卵圆孔未闭、高同型半胱氨酸血症、高凝状态、抗心磷脂抗体综合征、镰状细胞病、脑静脉窦血栓形成以及妊娠.此外,还有专门的章节对颅内出血后抗栓和抗凝治疗的应用以及指南的实施进行了讨论.

关键词：美国心脏协会声明心房颤动颈动脉狭窄高血压缺血短暂性脑缺血发作预防卒中

Pumping-induced Well Hydraulics and Groundwater Budget in a Leaky Aquifer System with Vertical Heterogeneity in Aquitard Hydraulic Properties

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Acta Geologica Sinica(English Edition) 2024年第2期98卷 477-490页

作者： ZHUAnG Chao LÜChenyang YAn Long LI Yabing ZHOU Zhifang WAnG Jinguo DOU Zhi walter A.ILLMAn School of Earth Sciences and Engineering Hohai UniversityNanjing 211100China School of Geography Earth and Environmental SciencesUniversity of BirminghamBirmingham B152TTU.K. Department of Modern Mechanics University of Science and Technology of ChinaHefei 230027China Department of Earth and Environmental Sciences University of WaterlooOntario N2L 3G1Canada

In groundwater hydrology,aquitard heterogeneity is often less considered compared to aquifers,despite its significant impact on groundwater hydraulics and groundwater resources evaluation.A semi-analytical solution is derived for pumping-induced well hydraulics and groundwater budget with consideration of vertical heterogeneity in aquitard hydraulic conductivity(K)and specific storage(S_(s)).The proposed new solution is innovative in its partitioning of the aquitard into multiple homogeneous sub-layers to enable consideration of various forms of vertically heterogeneous K or S_(s).Two scenarios of analytical investigations are explored:one is the presence of aquitard interlayers with distinct K or S_(s) values,a common field-scale occurrence;another is an exponentially depth-decaying aquitard S_(s),a regional-scale phenomenon supported by statistical *** investigations reveal that a low-K interlayer can significantly increase aquifer drawdown and enhance aquifer/aquitard depletion;a high-S_(s) interlayer can noticeably reduce aquifer drawdown and increase aquitard *** of low-K or high-S_(s) interlayers also significantly impact well hydraulics and groundwater *** the context of an exponentially depth-decaying aquitard S_(s),a larger decay exponent can enhance aquifer *** using current models with a vertically homogeneous aquitard,half the sum of the geometric and harmonic means of exponentially depth-decaying aquitard S_(s) should be used to calculate aquitard depletion and unconfined aquifer leakage.

关键词： hydrogeology aquitard vertical heterogeneity semi-analytical solution well hydraulics groundwater budget

Between Quantum Mechanics and General Relativity

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Journal of Modern Physics 2024年第8期15卷 1199-1228页

作者： walter James Christensen Jr. Department of Physics and Astronomy Cal Poly Pomona University Pomona USA

The origin of elementary particle mass is considered as a function of n-valued graviton quanta. To develop this concept we begin in a cold region of “empty space” comprised of only microscopic gravitons oscillating at angular frequency ω. From opposite directions enters a pair of stray protons. Upon colliding, heat and energy are released. Customarily, this phase and what follows afterward would be described by Quantum Chromodynamics (QCD). Instead, we argue for an intermediary step. One in which neighboring gravitons absorb discrete amounts of plane-wave energy. Captured by the graviton, the planewave becomes a standing wave, whereupon its electromagnetic energy densities are converted into gravitational quanta. Immediately thereafter an elementary particle is formed and emitted, having both mass and spin. From absorption to conversion to emission occurs in less than 3.7 × 10−16 s. During this basic unit of hybrid time, general relativity and quantum physics unite into a common set of physical laws. As additional stray protons collide the process continues. Over eons, vast regions of spacetime become populated with low-mass particles. These we recognize to be dark matter by its effects on large scale structures in the universe. Its counterpart, dark energy, arises when the conversion of gravitational quanta to particle emission is interrupted. This causes the gravitational quanta to be ejected. It is recognized by its large scale effects on the universe.

关键词： Dark Matter and Energy Gravitational Quanta Graviton Standing Wave Schwarzschild Metric General Relativity Quantum Physics Unified Field Theory Blackholes

Diet quality in patients with stroke

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Stroke & Vascular neurology 2019年第3期4卷 154-157页

作者： Jennifer L Dearborn Tehmina Khera Meghan Peterson Zartashia Shahab walter n.kernan Department of neurology Beth Israel Deaconess Medical CenterBostonMassachusettsUSA Department of neurology Yale UniversityNew HavenConnecticutUSA Department of Internal Medicine Yale University School of MedicineNew HavenConnecticutUSA

Objective A healthy diet is associated with reduced risk for stroke,myocardial infarction,cancer and *** examined the prevalence of a healthy diet in patients with a recent stroke or transient ischaemic attack(TIA).Methods We recruited a convenience sample of 95 patients with a recent ischaemic stroke or *** information from a 125-item Food Frequency Questionnaire,we calculated dietary quality and the percentage of patients meeting recommended daily intake(RDI)for common macronutrients and *** The mean age of patients was 66 years(SD:16)and 46%were women.39 patients(41%)were classified as having a healthy diet(35%of men and 48%of women).The majority of patients were within the RDI for carbohydrates(56.8%),total fat(61.1%),long-chain n-3 fats(68.4%),polyunsaturated fats(79.0%)and protein(96.8%).Very few patients consumed the recommended intake for sodium(25.3%),and even fewer consumed the RDI for potassium(4.2%),with the majority of patients consuming too much sodium and too little *** We found that most patients with recent stroke or TIA were not following a healthy diet before their stroke *** most patients,sodium intake was much above and potassium intake was much below RDI.

关键词： patients intake potassium

High density lipoprotein as a therapeutic target:Focus on its functionality

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BIOCELL 2023年第11期47卷 2361-2383页

作者： LEOnARDO GÓMEZ ROSSO BELÉn DAVICO EZEQUIEL LOZAnO CHIAPPE walter TETZLAFF LAURA BOERO FERnAnDO BRITES MAXIMILIAnO MARTÍn School of Pharmacy and Biochemistry Laboratory of Lipids and AtherosclerosisDepartment of Clinical BiochemistryUniversity of Buenos AiresNational Scientific and Technical Research Council(CONICET)Buenos Aires1113Argentina

Cardiovascular diseases(CVDs)are the leading cause of death *** are a group of disorders of the heart and blood vessels and include coronary heart disease,cerebrovascular disease and rheumatic heart disease among other *** are multiple independent risk factors for CVD,including hypertension,age,smoking,insulin resistance,elevated low-density lipoprotein cholesterol(LDL-C)levels,and triglyceride ***-C levels have traditionally been the target for therapies aimed at reducing CVD *** density lipoprotein(HDL)constitutes the only lipoprotein fraction with atheroprotective *** HDL-targeted therapies have focused on increasing HDL-C ***,clinical trials have shown that raising HDL-C with niacin failed to achieve CVD reduction.A possible explanation for these findings is that these drugs could interfere with lipid metabolism and cause alterations in HDL structure and composition,leading to loss of *** a result,targeting HDL-C levels would be insufficient to achieve CVD risk reduction,making HDL functionality a more desirable focus for HDL-directed *** are several drugs which show the potential to improve HDL *** drugs include molecules already approved for human use,such as statins and niacin,and particularly,compounds currently undergoing development such as apolipoprotein A-I mimetics and reconstituted HDL *** therapies show promising potential to improve HDL functionality *** therapeutic strategies should incorporate HDL functionality as a main target of interest.

关键词： HDL Cholesterol efflux rHDL Apo A-I mimetics Statins Paraoxonase

The secrets to running economy

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Journal of Sport and Health Science 2022年第3期11卷 273-274页

作者： walter Herzog Human Performance Laboratory Faculty of KinesiologyUniversity of CalgaryCalgaryAB T2N 1N4Canada

Every once in a while,a sport is revolutionized by a discovery or a new *** the mid-1980s,cross-country skiing was changed forever by the introduction of the skating *** Fosbury revolutionized high-jumping when he won the Olympic Games by crossing the bar“backwards”,and the development of the“klapp-skate”led to vast improvements of world records in speed skating.

关键词： technique. backward revolution

Continuous Finite Element Subgrid Basis Functions for Discontinuous Galerkin Schemes on Unstructured Polygonal Voronoi Meshes

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Communications in Computational Physics 2022年第6期32卷 259-298页

作者： walter Boscheri Michael Dumbser Elena Gaburro Department of Mathematics and Computer Science University of FerraraVia Machiavelli 3044121 FerraraItaly Department of Civil Environmental and Mechanical EngineeringUniversity of TrentoVia Mesiano 7738123 TrentoItaly Inria Univ.BordeauxCNRSBordeaux INPIMBUMR 5251200 Avenue de la Vieille Tour33405 Talence cedexFrance

We propose a new high order accurate nodal discontinuous Galerkin(DG)method for the solution of nonlinear hyperbolic systems of partial differential equations(PDE)on unstructured polygonal Voronoi *** than using classical polynomials of degree n inside each element,in our new approach the discrete solution is represented by piecewise continuous polynomials of degree n within each Voronoi element,using a continuous finite element basis defined on a subgrid inside each *** call the resulting subgrid basis an agglomerated finite element(AFE)basis for the DG method on general polygons,since it is obtained by the agglomeration of the finite element basis functions associated with the subgrid *** basis functions on each sub-triangle are defined,as usual,on a universal reference element,hence allowing to compute universal mass,flux and stiffness matrices for the subgrid triangles once and for all in a pre-processing stage for the reference element ***,the construction of an efficient quadrature-free algorithm is possible,despite the unstructured nature of the computational *** order of accuracy in time is achieved thanks to the ADER approach,making use of an element-local space-time Galerkin finite element *** novel schemes are carefully validated against a set of typical benchmark problems for the compressible Euler and navier-Stokes *** numerical results have been checked with reference solutions available in literature and also systematically compared,in terms of computational efficiency and accuracy,with those obtained by the corresponding modal DG version of the scheme.

关键词： Continuous finite element subgrid basis for DG schemes high order quadraturefree ADER-DG schemes unstructured Voronoi meshes comparison of nodal and modal basis compressible Euler and navier-Stokes equations

Does eccentric exercise stimulate sarcomerogenesis?

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Journal of Sport and Health Science 2022年第1期11卷 40-42页

作者： walter Herzog Heiliane de Brito Fontana Human Performance Laboratory Faculty of KinesiologyUniversity of CalgaryAB T2N 1N4Canada Department of Morphological Sciences School of Biological SciencesFederal University of Santa CatarinaFlorianopolis88040-900Brazil

Eccentric exercise has been associated with an increase in serial sarcomere number in some studies,1 but not in others.2 Similarly,increasing excursion of muscles resulted in sarcomerogenesis in some studies using growing animals,3 but not in others using skeletally mature animals.4 However,chronic elongation and chronic shortening appears to be a strong regulator of sarcomere number increase5,6 and decrease,5,7 respectively,in animal *** an abundance of research on the regulation of sarcomerogenesis under a variety of conditions,the mechanisms underlying in series sarcomere number adaptations in skeletal muscles remain a puzzle,especially in non-invasive human studies where measurements of sarcomerogenesis following interventions have not been possible to date.

关键词： spite has exercise