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Do age-associated changes of voltage-gated sodium channel isoforms expressed in the mammalian heart predispose the elderly to atrial fibrillation?

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World Journal of cardiology 2020年第4期12卷 123-135页

作者： Emmanuel Isaac Stephanie m cooper sandra A Jones mahmoud Loubani Department of cardiothoracic Surgery Hull University Teaching HospitalsCottingham HU165JQUnited Kingdom Department of Biomedical sciences University of HullHull HU67RXUnited Kingdom

Atrial fibrillation(AF)is the most common cardiac arrhythmia *** prevalence of the disease increases with age,strongly implying an age-related process underlying the *** a time when people are living longer than ever before,an exponential increase in disease prevalence is predicted *** unraveling the underlying mechanics of the disease is paramount for the development of innovative treatment and prevention *** role of voltage-gated sodium channels is fundamental in cardiac electrophysiology and may provide novel insights into the arrhythmogenesis of ***_v1.5 is the predominant cardiac isoform,responsible for the action potential *** studies have demonstrated that Na_v1.8(an isoform predominantly expressed within the peripheral nervous system)is responsible for cellular arrhythmogenesis through the enhancement of pro-arrhythmogenic *** studies have shown a decline in Na_v1.5 leading to a diminished action potential upstroke during phase ***,the study of human tissue demonstrates an inverse expression of sodium channel isoforms;reduction of Na_v1.5 and increase of Na_v1.8 in both heart failure and ventricular *** strongly suggests that the expression of voltage-gated sodium channels play a crucial role in the development of arrhythmias in the diseased *** aberrant sodium currents has led to novel therapeutic approaches in tackling AF and continues to be an area of emerging *** review will explore how voltage-gated sodium channels may predispose the elderly heart to AF through the examination of laboratory and clinical based evidence.

关键词： Voltage-gated Sodium channels Ageing Atrial fibrillation Nav1.5 Nav1.8 Late sodium current cardiac electrophysiology

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Thalidomide induces mucosal healing in crohn's disease: case report

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World Journal of Gastroenterology 2011年第45期17卷 5028-5031页

作者： márcio Rios Leite sandra Sousa Santos André castro Lyra Jaciane mota Genoile Oliveira Santana Department of Gastroenterology Prof. Edgard Santos University Hospital Federal University of Bahia Salvador Department of Gastrohepatology So Rafael Hospital Monte Tabor Foundation So Marcos Avenue

crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract that is defi ned by relapsing and remitting episodes. Tumor necrosis factor alpha (TNF-α) appears to play a central role in the pathophysiology of the disease. Standard therapies for inflammatory bowel disease fail to induce remission in about 30% of patients. Biological therapies have been associated with an increased incidence of infections, especially infection by mycobacterium tuberculosis (mtb). Thalidomide is an oral immunomodulatory agent with anti-TNF-α properties. Recent studies have suggested that thalidomide is effective in refractory luminal and fistulizing crohn's disease. Thalidomide costimulates T lymphocytes, with greater effect on cD8+ than on cD4+ T cells, which contributes to the protective immune response to mtb infection. We present a case of crohn's disease with gastric, ileal, colon and rectum involvement as well as steroid dependency, which progressed with loss of response to infliximabafter three years of therapy. The thorax computed tomography scan demonstrated a pulmonary nodule suspected to be mtb infection. The patient was started on thalidomide therapy and exhibited an excellent response.

关键词： Anti-tumor necrosis factor alpha crohn’s disease mucosal healing mycobacterium tuberculosis Thalidomide

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contested incrementalism: Elemental’s Quinta monroy settlement fifteen years on

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Frontiers of Architectural Research 2021年第2期10卷 263-273页

作者： David O’Brien sandra carrasco Faculty of Architecture Building and PlanninsThe University of MelbourneMelbourneAustralia school of Architecture and Built Environment University of NewcastleAustralia

Quinta monroy is an award-winning co-designed settlement for 93 families on half a hectare of land at Iquique in northern ***,complaints about the disorderly settlement peaked after the landowner^death and provoked untenured residents to seek government subsidies to redevelop the *** 2003,a government social housing project was coordinated by the,,Elementar,architecture firm with US$10,000 per *** the residenfs temporary relocation,93 modular and interlinked apartments were built around a series of *** apartments,which were designed as,fhalf-houses,m were subsequently co-opted by residents adding rooms in locations planned in advance by *** households have since doubled the size of their apartment and reformed the settlement in ways not anticipated by *** paper details a spatial and ethnographic study of the Quinta monroy settlement since redevelopment to identify opportunities and risks that accompany this type of social housing *** study reveals evidence that residents,capacities to enlarge apartments commonly exceeds the architects expectations and that unregulated expansions often compromise the settlements *** research anticipates further opportunities for expansion in this semi-regulated settlement and investigates possibilities that another contested slum settlement may emerge.

关键词： Social housing Incremental development co-design Aravena chile

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Non-alcoholic fatty liver disease and obesity: Biochemical, metabolic and clinical presentations

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World Journal of Gastroenterology 2014年第28期20卷 9330-9337页

作者： sandra milic Davorka Lulic Davor Stimac Division of Gastroenterology Department of Internal MedicineUniversity Hospital Rijeka

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BmI) > 30 kg/m2. However, the distribution of fat tissue plays a greater role in insulin resistance than the BmI. The large amount of visceral adipose tissue (VAT) in morbidly obese (BmI > 40 kg/m2) individuals contributes to a high prevalence of NAFLD. Free fatty acids derived from VAT tissue, as well as from dietary sources and de novo lipogenesis, are released to the portal venous system. Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD. In addition, secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways, which are also activated by free fatty acids, and contribute to insulin resistance. most NAFLD patients are asymptomatic on clinical presentation, even though some may present with fatigue, dyspepsia, dull pain in the liver and hepatosplenomegaly. Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications, anti-obesity medication and bariatric surgery. This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease. The relative contribution of visceral and liver fat to insulin resistance is discussed, and recommendations for clinical evaluation of affected individuals is provided.

关键词： Fatty liver Insulin resistance Intra-abdominal fat metabolism Non-alcoholic fatty liver disease Obesity

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methods and parameters of melting curve analysis for identification of Leishmania species:A scoping review

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Asian Pacific Journal of Tropical medicine 2021年第12期14卷 528-542页

作者： Juliana J G Ferreira Fernanda S Nascimento Glaucia E B marcon Eros A de Almeida sandra c B costa Laboratório de Diagnóstico de Doenças Infecciosas por Técnicas de Biologia molecular Departamento de Clínica MédicaFaculdade de Ciências MédicasUniversidade Estadual de Campinas(UNICAMP)Campinas13083-887SPBrazil Fundação Oswaldo cruz mato Grosso do Sul(FIOcRUZ mS) Rua Gabriel Abrão92Jardim das NaçõesCampo Grande79081-746 MSBrazil Grupo de Estudos em Doença de chagas Departamento de Clínica MédicaFaculdade de Ciências MédicasUniversidade Estadual de Campinas(UNICAMP)Campinas13083-887SPBrazil

Leishmaniasis is a set of diseases with a worldwide distribution that affects mainly economically underprivileged populations in developing countries. It has a major impact on public health, with a global cost of billions of dollars per year. The treatment and control of leishmaniasis vary according to the Leishmania species involved, which require reliable methods for species identification. Since most of the currently used methods have limitations, there is a need for assays that allow rapid, precise identification of the offending species. Real-time polymerase chain reactions in conjunction with dissociation curve analysis have been used to detect differences in the DNA composition of selected genes of Leishmania spp. Kinetoplast DNA is the main molecular target used because of its high copy number per parasite, but other targets have also been studied. As part of an effort to establish melting temperature standards for each target gene, we have reviewed the pertinent literature available in public databases, including Pub med, Web of science, sci ELO and LILAcS, using the keywords "Leishmania", "leishmaniasis", "realtime PcR", "melting temperature", and "melting curve", alone or in combination. After applying eligibility criteria, 27 articles were selected for analysis. A considerable variation in the methodologies analyzed was found regarding molecular targets, standardization of the methods, reproducibility and specificity. Because of this, statistical analysis was not performed. In most cases, the methods were able to differentiate the parasite at the subgenus level or few species regardless of the target chosen.

关键词： Leishmaniasis melting temperature Real-time PcR

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Nano to micro size transition of hydroxyapatite in porcine bone during heat treatment with low heating rates

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Progress in Natural science:materials International 2020年第4期30卷 494-501页

作者： Angélica m.castillo-Paz sandra m.Londo?o-Restrepo Liliana Tirado-mejía m.A.mondragón mario E.Rodríguez-García Grupo de Optoelectrónica Instituto Interdisciplinario de las Ciencias Universidad del Quindío centro de Investigación y de Estudios Avanzados del IPN Departamento de Nanotecnología Centro de Física Aplicada y Tecnología Avanzada Universidad Nacional Autónoma de México Campus Juriquilla

This work focuses on the changes of raw hydroxyapatite obtained from porcine bones during heat treatment with heating rates of 2.5 and 5.0 °c/min between 600 °c and 1100 °c. High-Resolution transmission electron microscopy(HR-TEm) images showed that raw hydroxyapatite was formed by high-ordered nanometric platelet crystals with a length of around 18 nm and width around 7 nm. High-Resolution scanning electron microscopy(HR-SEm) images evidenced the coalescence phenomena during heating giving. It was found that the growth of the crystals and the transition from nano to a micro-size occurred at around 700 °c. And the changes in the full width at half maximum(FWHm) for the characteristic(002) plane of the X-ray diffraction patterns and the FWHm of the characteristic Raman band at 960 cm-1 for ν1 PO43-exhibited the transition from nano to a micro size, that was confirmed by HR-SEm images and the thermogravimetric(TG) analysis. The porosity of the BIOHAp changes from intra nanometric to intercrystalline.

关键词： Bone composition Hydroxyapatite nanoparticles mineral composition Porosity formation Raman analysis

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curcumin-loaded polymeric nanoparticles for neuro-protection in neonatal rats with hypoxic-ischemic encephalopathy

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Nano Research 2018年第10期11卷 5670-5688页

作者： Andrea Joseph Thomas Wood chih-chung chen Kylie corry Jessica m. Snyder sandra E. Juul Pratik Parikh Elizabeth Nance Department of chemical Engineering University of Washington Seattle WA 98195 USA Division of Neonatology Department of Pediatrics University of Washington Seattle WA 98195 USA Department of comparative medicine University of Washington Seattle WA 98195 USA Department of Radiology University of Washington Seattle WA 98195 USA

Hypoxic-ischemic encephalopathy is the leading cause of permanent brain injury in term newborns and currently has no cure. Inflammatory processes play a key role in the progression of this disease and may be amenable to a targeted pharmaceutical intervention. curcumin is a dietary compound with potent anti-inflammatory, antioxidant, and antiapoptotic properties but is limited in therapeutic applications due to its low aqueous solubility, low bioavailability, and rapid first-pass hepatic metabolism. To address these limitations, loading curcumin into poly（lactic-co-glycolic acid）-poly（ethylene glycol）（PLGA-PEG） nanoparticles may increase relevant pharmacokinetic parameters and allow for effective drug delivery to the brain. Using the Vannucci model of unilateral hypoxic-ischemic brain injury in neonatal rats, we studied the in vivo effect of curcumin-loaded PLGA-PEG nanoparticles on brain uptake and diffusion of curcumin and on neuroprotection. The curcumin-loaded nanoparticles were able to overcome the impaired blood-brain barrier, diffuse effectively through the brain parenchyma, localize in regions of injury, and deliver a protective effect in the injured neonatal brain. The application of curcumin and PLGA-PEG nanoparticle-mediated delivery to a clinically relevant model of neonatal brain injury provides greater opportunities for clinical translation of targeted therapies for hypoxic-ischemic encephalopathy.

关键词： drug delivery neuroprotection brain penetrating neonatal hypoxia-ischemia curcumin nanotherapeutics

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Transcranial magnetic stimulation: potential treatment for co-occurring alcohol, traumatic brain injury and posttraumatic stress disorders

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Neural Regeneration Research 2014年第19期9卷 1712-1730页

作者： Amy A.Herrold sandra L.Kletzel Brett c.Harton R.Andrew chambers Neil Jordan Theresa Louise-Bender Pape Edward Hines Jr.VA Hospital Research Service PO Box 5000 (M/C 151H)HinesILUSA The Department of Veterans Affairs (VA) Center for Innovation for Complex Chronic HealthcareEdward Hines Jr.VA HospitalPO Box 5000 (M/C 151H)HinesILUSA Department of Psychiatry & Behavioral sciences Northwestern University Feinberg School of Medicine446 East Ontario#7-200ChicagoILUSA chicago Association for Research and Education in science HinesILUSA Department of Psychiatry Laboratory for Translational Neuroscience of Dual Diagnosis & DevelopmentNeuroscience Research CenterIndiana University School of Medicine320 West 15~(th)StreetIndianapolisINUSA Northwestern University Feinberg school of medicine Department of Physical Medicine and RehabilitationOffice of Medical Educ.(1574)345 E.Superior St.ChicagoILUSA

Alcohol use disorder （AUD）, mild traumatic brain injury （mTBI）, and posttraumatic stress disorder （PTSD） commonly co-occur （AUD ＋ mTBI ＋ PTSD）. These conditions have overlapping symptoms which are, in part, reflective of overlapping neuropathology. These conditions become problematic because their co-occurrence can exacerbate symptoms. Therefore, treatments must be developed that are inclusive to all three conditions. Repetitive transcranial magnetic stimulation （rTmS） is non-invasive and may be an ideal treatment for co-occurring AUD ＋ mTBI ＋ PTSD. There is accumulating evidence on rTmS as a treatment for people with AUD, mTBI, and PTSD each alone. However, there are no published studies to date on rTmS as a treatment for co-occurring AUD ＋ mTBI ＋ PTSD. This review article advances the knowledge base for rTmS as a treatment for AUD ＋ mTBI ＋ PTSD. This review provides background information about these co-occurring conditions as well as rTmS. The existing literature on rTmS as a treatment for people with AUD, TBI, and PTSD each alone is reviewed. Finally, neurobiological findings in support of a theoretical model are discussed to inform TmS as a treatment for co-occurring AUD ＋ mTBI ＋ PTSD. The peer-reviewed literature was identified by targeted literature searches using Pubmed and supplemented by cross-referencing the bibliographies of relevant review articles. The existing evidence on rTmS as a treatment for these conditions in isolation, coupled with the overlapping neuropathology and symptomology of these conditions, suggests that rTmS may be well suited for the treatment of these conditions together.

关键词： transcranial magnetic stimulation traumatic brain injury posttraumatic stress disorder treatment neuroimaging substance use disorders addiction co-morbidity mental health disorders behavioral health neuroimaging non-invasive brain stimulation

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cardiovascular rehabilitation in patients aged 70-year-old or older:benefits on functional capacity,physical activity and metabolic profile in younger *** patients

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Journal of Geriatric cardiology 2020年第9期17卷 544-553页

作者： marta Fontes-Oliveira maria Trêpa Patrícia Rodrigues Preza Fernandes sandra magalhães Sofia cabral mário Santos Severo Torres cardiology Department University Hospital Centre of PortoPortoPortugal cardiac Rehabilitation Unit Cardiology DepartmentUniversity Hospital Centre of PortoPortoPortugal Pulmonary Vascular Disease Unit University Hospital Centre of PortoPortoPortugal

Background The benefits of exercise-based cardiac rehabilitation(EBcR)programs in post-acute myocardial infarction(AmI)patients have been *** aim was to assess the impact of EBcR in³70-years-old *** post-AmI *** We retrospectively evaluated patients who underwent a supervised EBcR protocol,twice a week during 6-12 *** evaluated changes in several outcomes based on pre-and post-cRP *** Of a total of 1607 patients,333(21%)were³*** the EBcR,an overall improvement on functional capacity,daily physical activity,lipid profile,body mass index,glycated hemoglobin(HbA1c),N-terminal pro-brain natriuretic peptide(NT-pro-BNP)and c-reactive protein was observed in both younger and older patients(Pmaller benefit on the increment of daily physical activity and lipid profile improvement,but a larger reduction in *** the multivariate analysis,only improvements on daily physical activity and HbA1c were dependent on *** As their younger counterparts,older patients,significantly improved functional capacity,metabolic parameters and level of daily physical activity after EBcR.

关键词： Aging cardiovascular prevention Exercise-based cardiac rehabilitation

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Influence of parameters on the microstructure of a duplex stainless steel joint welded by a GmAW welding process

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Progress in Natural science:materials International 2022年第4期32卷 415-423页

作者： sandra chacón-Fernández Antonio Portolés García Gerardo Romaní Labanda Universidad Politécnica de madrid Escuela Técnica Superior de Ingenieros Industriales UPM

Duplex stainless steels（DSSs） are widely used in industry for their desirable properties. Any fusion welding technique modifies the microstructure and, consequently, the properties of the material. This paper presents a parametric study of the variables that determine the energy contribution（current, voltage and welding speed） and the structural modifications produced during gas metal arc welding. The analysis comprises metallographic study,phase balance, dimensioning of the weld beads and tensile and hardness tests. The influence of the variables studied on the thermal cycles obtained（temperatures reached and cooling rate） was determined by using a finite element model. The results showed that, in addition to the indicated parameters, the parameter power transfer per volume（W/m3） and the geometry in the bead must be controlled due to their influence on the heat flow distribution and phase balance.

关键词： Welding Heat input GmAW Duplex stainless steels (DSS) Finite element model (FEm)

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