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ISCHEMIA trial:How to apply the results to clinical practice

World Journal of Cardiology 2021年第8期13卷 237-242页

作者： Rafael Vidal-Perez Alberto Bouzas-Mosquera Jesus Peteiro Jose Manuel Vazquez-Rodriguez Servicio de Cardiologia Unidad de Imagen y Funcion CardiacaComplexo Hospitalario Universitario A Coruna(CHUAC)Centro de Investigacion Biomedica en Red(CIBERCV)-Instituto de Salud Carlos IIIA Coruna 15006Spain Servicio de Cardiología Complexo Hospitalario Universitario A CoruñaA Coruña 15006Spain

During the last years two questions have been continuously asked in chronic coronary syndromes:(1)Do revascularization procedures(coronary artery bypass grafting or percutaneous coronary intervention)really improve symptoms of angina?and(2)Do these techniques improve outcomes,*** they prevent new myocardial infarction events and cardiovascular death?Therefore,there was a need for a large definitive *** study was the ISCHEMIA trial,a large,multicentric trial sponsored by the National Heart,Lung,and Blood *** main trial compared coronary revascularization and optimal medical treatment(OMT)vs OMT alone in 5179 patients enrolled after a stress *** a median 3.2-year follow-up,318 primary outcome events occurred;the adjusted hazard ratio for the invasive strategy as compared with the conservative strategy was 0.93(95%confidence interval 0.80-1.08,P=0.34).The ISCHEMIA trial deeply disrupted many of our prior attitudes regarding management strategies for patients with stable coronary artery *** findings underscore the benefits of disease-modifying OMT for stable coronary artery disease *** main purposes of ischemia assessment before this trial were:Diagnostic purposes,assessment of outcome,and adding to decision-making ***,this changed after the trial *** results of ISCHEMIA might challenge the current diagnostic approach for stable angina patients recommended in the last European Society of Cardiology guidelines on chronic coronary disease that were based on studies published before the ISCHEMIA *** this editorial we propose our approach based on the ISCHEMIA study and the pretest probability for a positive test in patients with chronic coronary syndromes.

关键词： Stable angina Chronic coronary syndrome ISCHEMIA Stress testing Therapy Diagnosis

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The Iberian Roma Population Variant Server(IRPVS)

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Journal of Genetics and Genomics 2024年第7期51卷 769-773页

作者： Fabiola Mavillard Javier Perez-Florido Francisco M.Ortuño Amador Valladares Miren L.Álvarez-Villegas Gema Roldán Rosario Carmona Manuel Soriano Santiago Susarte Pilar Fuentes Daniel López-López Ana María Nuñez-Negrillo Alejandra Carvajal Yolanda Morgado Daniel Arteaga Rosa Ufano Pablo Mir Juan F.Gamella Joaquín Dopazo Carmen Paradas Macarena Cabrera-Serrano instituto de Biomedicina de Sevilla(IBiS) Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaSpain Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud CarlosⅢSevillaSpain Plataforma Andaluza de Medicina Computacional Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevillaSpain Grupo de medicina computacional de sistemas Instituto de Biomedicina de Sevilla(IBiS)Hospital Virgen del RocíoSevillaSpain Nodo de Genómica Funcional (INB-ELIXIR-es)Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevilla 41013Spain Bioinformática en Enfermedades raras(BiER) Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER)Instituto de salud CarlosⅢSevillaSpain departamento de Ingeniería de Computadores Automática y RobóticaUniversidad de GranadaGranadaSpain Servicio de Urgencias de Atención Primaria Distrito SevillaSevillaSpain Centro de Servicios Sociales Negociado de Servicios EspecializadosAyuntamiento de SevillaSevillaSpain departamento de Enfermería Facultad de Ciencias de la SaludUniversidad de GranadaGranadaSpain departamento de Neurología Hospital Virgen de las NievesGranadaSpain departamento de Neurología Hospital Virgen de ValmeSevillaSpain Centro de salud Utrera Sur SevillaSpain Centro de salud Polígono Sur SevillaSpain Unidad de Trastornos del Movimiento Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain departamento de Medicina Facultad de MedicinaUniversidad de SevillaSevilleSpain departamento de Antropología Social Universidad de GranadaSpain Unidad Enfermedades Neuromusculares Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain

In recent years,the number of known disease genes has exponentially grown due to the widespread adoption of cost-effective massive parallel *** identify new disease variants,especially in monogenic disorders,a frequen... 详细信息

关键词： Server filtering massive

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Insight into endoplasmic reticulum-mitochondria contacts in human amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第7期19卷 1407-1408页

作者： Naomi Hartopp Andrea Markovinovic Christopher CJ Miller Patricia Gomez-Suaga Sheffield Institute for Translational Neuroscience University of SheffieldSheffieldUK department of Basic and Clinical Neuroscience Institute of PsychiatryPsychology and NeuroscienceLondonUK Universidad de Extremadura.departamento de Bioquímica y Biología Molecular y Genética Facultad de Enfermería y Terapia OcupacionalCáceresSpain Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas-instituto de salud carlos ⅲ(CIBER-CIBERNED-ISCⅢ) MadridSpain instituto Universitario de Investigación Biosanitaria de Extremadura(INUBE) CáceresSpain

Amyotrophic lateral sclerosis(ALS) is a fastprogressing fatal neurodegenerative disease and the most common form of motor neuron *** is currently no cure and approximately 90% of cases are *** shares genetic causes,clinical and neuropathological features with frontotemporal dementia,the second most common form of presenile *** and frontotemporal dementia are therefore considered a disease spectrum(Abramzon et al.,2020).

关键词： senile sclerosis

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Prevalence of hepatocarcinoma-related hepatitis B virus mutants in patients in grey zone of treatment

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World Journal of Gastroenterology 2019年第38期25卷 5883-5896页

作者： Ana Isabel Gil-García Antonio Madejón Irene Francisco-Recuero Ana López-López Emiliana Villafranca Miriam Romero Araceli García Antonio Olveira Rocío Mena Juan Ramón Larrubia Javier García-Samaniego Hepatology Unit Hospital Universitario La PazMadrid 28046Spain Centro de Investigación Biomédica en Red Instituto de Salud Carlos IIIMadrid 28029Spain instituto de Investigación del Hospital Universitario la Paz Madrid 28046Spain Biochemistry department Faculty of MedicineUniversidad Autónoma de MadridMadrid 28029Spain instituto de Genética Médica y Molecular Hospital Universitario La PazMadrid 28046Spain Translational Hepatology Unit Hospital General Universitario de GuadalajaraGuadalajara 19002Castilla-La ManchaSpain

BACKGROUND Antiviral treatment of patients with chronic hepatitis B(CHB)in the grey zone of treatment comands risk management in order to optimize the health *** this sense,the identification of HBV mutants related with an increased risk of hepatocellular carcinoma(HCC)could be useful to identify subpopulations with potential indication of antiviral *** To analyze the prevalence/persistence of hepatitis B virus(HBV)preS and basal core promoter(BCP)/precore/core variants associated to HCC development in CHB patients in the grey *** Work was designed as a longitudinal retrospective study,including 106 plasma samples from 31 patients with CHB in the grey zone of treatment:Hepatitis B e antigen negative,HBV-DNA levels between 12-20000 IU/mL,normal or discordant transaminase levels during follow up and mild/moderate necroinflammatory activity in liver biopsy or Fibroscan(up to 9.5 kPa).Serum HBVDNA was tested using the Abbott Real Time HBV Assay and the BCP/precore/core and the hepatitis B surface antigen(HBsAg)coding regions were analyzed in positive samples by PCR/bulk-sequencing to identify the HCCrelated HBV *** High-risk HCC related mutants were detected in 24(77%)patients:19(61%)in the BCP/precore/core,and 7(23%)in the HBsAg coding region(2 preS1 and 5 preS2 deletions).The prevalence of preS deletions was genotype-dependent:3/5(60%)patients with preS2 deletions and 1/2 with preS1 deletions were infected with the HBV-E *** HBV-E was the most prevalent in sub-Saharan patients,a correlation between preS deletions and ethnicity was also found:6/8(75%)sub-Saharan vs 1/19(5%)Caucasian patients had preS deletions(P=0.00016).Remarkably,this correlation was maintained in those patients infected with HBV-A,a minor genotype in sub-Saharan patients:2/2 patients infected with HBV-A from West Africa vs 0/6 of Caucasian origin had preS *** HCC related variants were the major strains and persisted over time(up to 48 mo).Pa

关键词： Hepatitis B virus Hepatocellular carcinoma PreS deletions Hepatitis B virus treatment Grey zone

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Bone marrow-derived mononuclear stem cells in the treatment of retinal degenerations

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Neural Regeneration Research 2022年第9期17卷 1937-1944页

作者： Diego García-Ayuso Johnny Di Pierdomenico David García-Bernal Manuel Vidal-Sanz María P.Villegas-Pérez departamento de Oftalmología Facultad de MedicinaUniversidad de MurciaCampus de Ciencias de la saludMurciaSpain instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca(IMIB-Virgen de la Arrixaca) MurciaSpain Servicio de Hematología Hospital Clínico Universitario Virgen de la ArrixacaMurciaSpain

Retinal degenerative diseases affecting the outer retina in its many forms(inherited,acquired or induced)are characterized by photoreceptor loss,and represent currently a leading cause of irreversible vision loss in the *** present,there are very few treatments capable of preventing,recovering or reversing photoreceptor degeneration or the secondary retinal remodeling,which follows photoreceptor loss and can also cause the death of other retinal ***,these diseases are nowadays one of the greatest challenges in the field of ophthalmological *** marrow derived-mononuclear stem cell transplantation has shown promising results for the treatment of photoreceptor *** cells may have the potential to slow down photoreceptor loss,and therefore should be applied in the early stages of photoreceptor ***,because of their possible paracrine effects,they may have a wide range of clinical applications,since they can potentially impact on several retinal cell types at once and photoreceptor degenerations can involve different cells and/or begin in one cell type and then affect adjacent *** intraocular injection of bone marrow derived-mononuclear stem cells also enhances the outcomes of other treatments aimed to protect ***,it is likely that future investigations may combine bone marrow derived-mononuclear stem cell therapy with other systemic or intraocular treatments to obtain greater therapeutic effects in degenerative retinal diseases.

关键词： age-related macular degeneration bone marrow stem cells intravitreal injection macroglia microglia photoreceptor degeneration retinal ganglion cells retinitis pigmentosa subretinal injection transplant

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Comparison of biological fitness in crosses between subspecies of Meccus phyllosomus （Hemiptera： Reduviidae： Triatominae） in southern Mexico

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Insect Science 2017年第1期24卷 114-121页

作者： Jose Alejandro Martinez-Ibarra Benjamin Nogueda-Torres Luis Fernando Salazar-Montano Juan carlos Garcia-Lino demver Arroyo-Reyes Juan Angel Hernandez-Navarro Area de Entomologia Medica Universidad de Guadalajara Ciudad Guzman Jalisco Mexico Becario de COFAA Escuela Nacional de Ciencias Biologicas Instituto Politecnico Nacional D.F. Mexico Carrera de Medicina Departamento de Salud y Bienestar Centro Universitario del Sur Universidad de Guadalajara Ciudad Guzman Jalisco Mexico

Understanding the biological parameters of some triatomine subspecies of Meccus phyllosomus （Burmeister） is a crucial first step in estimating the epidemiologie importance of this group. Biological parameters related to hatching, lifetime, number of blood meals to molt, percentage of females at the end of the cycle, number of laid eggs, and mortality for each instar of 3 M. phyllosomus subspecies [M. p. mazzottii （Usinger）, M. p. pallidipennis （Stal）, and M. p. phyllosomus] and their laboratory hybrids were evaluated and compared. No significant differences （P 〉 0.05） were found among the experimental hybrids （MaPa, MaPhy, PaPhy） and reciprocal cohorts. In 5 （hatching, number of blood meals to molt, accumulative mortality, percentage of females, and mean number of laid eggs） of the 6 studied parameters （with the exception of development time）, the hybrid cohorts had better fitness results than the parental cohorts involved in each set of crosses. The increase in hybrid fitness found in our study could lead to an increase in the epidemiologic risks caused by transmission of Trypanosoma cruzi to humans.

关键词： biological parameters Chagas disease Meccus subspecies Mexico tri- atomines Trypanosoma cruzi transmission

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SNARE complex in axonal guidance and neuroregeneration

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Neural Regeneration Research 2018年第3期13卷 386-392页

作者： Fausto Ulloa Tiziana Cotrufo delia Ricolo Eduardo Soriano Sofia J. Araújo department of Cell Biology Physiology and Immunology School of Biology and Institute of Neurosciences University of Barcelona Barcelona Spain Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Instituto de Salud Carlos III (ISCIII) Madrid Spain Institut de Biologia Molecular de Barcelona (IBMB-CSIC) Parc Cientific de Barcelona Barcelona Spain department of Genetics Microbiology and Statistics School of Biology University of Barcelona Barcelona Spain Vail d 'Hebron Institut de Recerca (VHIR) Barcelona Spain

Through complex mechanisms that guide axons to the appropriate routes towards their targets, axonal growth and guidance lead to neuronal system formation. These mechanisms establish the synaptic circuitry necessary for the optimal performance of the nervous system in all organisms. Damage to these networks can be repaired by neuroregenerative processes which in turn can re-establish synapses between injured axons and postsynaptic terminals. Both axonal growth and guidance and the neuroregenerative response rely on correct axonal growth and growth cone responses to guidance cues as well as correct synapses with appropriate targets. With this in mind, parallels can be drawn between axonal regeneration and processes occurring during embryonic nervous system development. However, when studying parallels between axonal development and regeneration many questions still arise; mainly, how do axons grow and synapse with their targets and how do they repair their membranes, grow and orchestrate regenerative responses after injury. Major players in the cellular and molecular processes that lead to growth cone development and movement during embryonic development are the Soluble N-ethylamaleimide Sensitive Factor （NSF） Attachment Protein Receptor （SNARE） proteins, which have been shown to be involved in axonal growth and guidance. Their involvement in axonal growth, guidance and neuroregeneration is of foremost importance, due to their roles in vesicle and membrane trafficking events. Here, we review the recent literature on the involvement of SNARE proteins in axonal growth and guidance during embryonic development and neuroregeneration.

关键词： SNARE vesicle associated membrane protein synaptosomal associated protein axon guidance neuroregeneration nervous system cell membrane

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Toll-like receptor 4 polymorphisms and bacterial infections in patients with cirrhosis and ascites

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World Journal of Hepatology 2018年第1期10卷 124-133页

作者： Edilmar Alvarado-Tapias carlos Guarner-Argente Elida Oblitas Elisabet Sánchez Silvia Vidal Eva Román Mar Concepción Maria Poca Cristina Gely Oana Pavel Juan Camilo Nieto Cándido Juárez carlos Guarner Germán Soriano department of Gastroenterology Hospital de la Santa Creu i Sant PauBarcelona 08025Spain instituto de salud carlos III Institut de Recerca IIBSant PauUniversitat Autònoma de BarcelonaBellaterra(Cerdanyola del Vallès)08193Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadrid 28029Spain department of Immunology Hospital de la Santa Creu i Sant PauBarcelona 08025Spain Escola Universitària d’Infermeria EUI-Sant Pau Hospital de la Santa Creu i Sant PauBarcelona 08025Spain

AIM To assess the relationship between the presence of toll-like receptor 4(TLR4) polymorphisms and bacterial infections in cirrhotic patients with ascites. METHODS We prospectively included consecutive patients with cirrhosis and ascites hospitalized during a 6-year period. Patients with human immunodeficiency virus(HIV) infection or any other immunodeficiency, patients with advanced hepatocellular carcinoma(beyond Milan's criteria) or any other condition determining poor short-term prognosis, and patients with a permanent urinary catheter were excluded. The presence of D299 G and/or T399 I TLR4 polymorphisms was determined by sequencing and related to the incidence and probability of bacterial infections, other complications of cirrhosis, hepatocellular carcinoma, and mortality during follow-up. A multivariate analysis to identify predictive variables of mortality in the whole series was performed. RESULTS We included 258 patients: 28(10.8%) were carriers of D299G and/or T399I TLR4 polymorphisms(polymorphism group) and 230 patients were not(wildtype group). The probability of developing any bacterial infection at one-year follow-up was 78% in the polymorphism group and 69% in the wild-type group(P = 0.54). The one-year probability of presenting infections caused by gram-negative bacilli(51% vs 44%, P = 0.68), infections caused by gram-positive cocci(49% vs 40%, P = 0.53), and spontaneous bacterial peritonitis(29% vs 34%, respectively, P = 0.99) did not differ between the two groups. The oneyear probability of transplant-free survival was 55% in the polymorphism group and 66% in the wild-type group(P = 0.15). Multivariate analysis confirmed that age, Child-Pugh score, active alcohol intake, previous hepatic encephalopathy, hepatocellular carcinoma and serum creatinine were associated with a higher risk of death during follow-up. CONCLUSION Genetic polymorphisms D299 G and/or T399 I of TLR4 do not seem to play a relevant role in the predisposition of cirrhotic patie

关键词： Cirrhosis Genetic polymorphisms Toll-like receptor 4 Bacterial infections Ascites

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Hypoglycemia associated with fluoxetine treatment in a patient with type 1 diabetes

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World Journal of Clinical Cases 2013年第5期1卷 169-171页

作者： Betina Biagetti Rosa Corcoy Servei d’Endocrinologia i Nutrició Hospital de la Santa Creu i Sant Pau Avgda Sant Antoni M Claret 167 08025 Barcelona Spain departament de Medicina Universitat Autònoma de Barcelona 08193 Belllaterra Spain CIBER Bioengineering Biomaterials and Nanotechnology Instituto de Salud Carlos Ⅲ 28029 Madrid Spain

We report on a patient with type 1 diabetes mellitus who presented with recurrent episodes of hypoglycemia and a marked reduction in her daily insulin requirements after introduction of fluoxetine. This 25-yearold Caucasian woman had been followed up at the outpatient clinic for type 1 diabetes mellitus and prepregnancy care. She used a continuous subcutaneous insulin infusion with lispro and her daily insulin dose was 0.5 IU/kg per day. She had no chronic diabetic complications or hypoglycemia unawareness. Fluoxetine at a daily dose of 20 mg had been started because of depressive symptoms and within one week, she presented recurrent hypoglycemic episodes that prompted a progressive reduction in the insulin dose down to 0.3 IU/kg per day. The reduced insulin requirements continued during the period of fluoxetine treatment while glycated hemoglobin remained stable. She had no concurrent additional cause to explain the reduced insulin requirements. After fluoxetine was stopped, insulin re-quirements progressively increased and returned to the patient′s usual dose.

关键词： Fluoxetine Selective serotonin-reuptake inhibitor Hypoglycemia Diabetes mellitus

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Clinical applications of high-throughput genetic diagnosis in inherited retinal dystrophies: Present challenges and future directions

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World Journal of Medical Genetics 2015年第2期5卷 14-22页

作者： Gemma Marfany Roser Gonzàlez-Duarte departament de Genètica Facultat de Biologia Universitat de Barcelona CIBER Instituto de Salud Carlos Ⅲ IBUB Institut de Biomedicina de la Universitat de Barcelona

The advent of next generation sequencing(NGS) tech-niques has greatly simplified the molecular diagnosis and gene identification in very rare and highly heterogeneous Mendelian disorders. Over the last two years, these approaches, especially whole exome sequencing(WES), alone or combined with homozygosity mapping and linkage analysis, have proved to be successful in the identification of more than 25 new causative retinal dystrophy genes. NGS-approaches have also identified a wealth of new mutations in previously reported genes and have provided more comprehensive information concerning the landscape of genotype-phenotype correlations and the genetic complexity/diversity of human control populations. Although whole genome sequencing is far more informative than WES, the functional meaning of the genetic variants identified by the latter can be more easily interpreted, and final diagnosis of inherited retinal dystrophies is extremely successful, reaching 80%, particularly for recessive cases. Even considering the present limitations of WES, the reductions in costs and time, the continual technical improvements, the implementation of refined bioinformatic tools and the unbiased comprehensive genetic information it provides, make WES a very promising diagnostic tool for routine clinical and genetic diagnosis in the future.

关键词： Next generation sequencing Identification of novel causative genes Inherited retinal dystrophies Genetic diagnosis Whole exome sequencing

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