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new insights into the pathophysiology of achalasia and implications for future treatment

World Journal of Gastroenterology 2016年第35期22卷 7892-7907页

作者： Janette Furuzawa-Carballeda Samuel Torres-Landa miguel ángel Valdovinos Enrique Coss-Adame Luis A martín del Campo Gonzalo Torres-Villalobos department of Immunology and Rheumatology Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán department of Experimental Surgery Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Idiopathic achalasia is an archetype esophageal motor disorder, causing significant impairment of eating ability and reducing quality of life. The pathophysiological underpinnings of this condition are loss of esophageal peristalsis and insufficient relaxation of the lower esophageal sphincter(LES). The clinical manifestations include dysphagia for both solids and liquids, regurgitation of esophageal contents, retrosternal chest pain, cough, aspiration, weight loss and heartburn. Even though idiopathic achalasia was first described more than 300 years ago, researchers are only now beginning to unravel its complex etiology and molecular pathology. The most recent findings indicate an autoimmune component, as suggested by the presence of circulating anti-myenteric plexus autoantibodies, and a genetic predisposition, as suggested by observed correlations with other well-defined genetic syndromes such as Allgrove syndrome and multiple endocrine neoplasia type 2 B syndrome. Viral agents(herpes, varicella zoster) have also been proposed as causative and promoting factors. Unfortunately, the therapeutic approaches available today do not resolve the causes of the disease, and only target the consequential changes to the involved tissues, such as destruction of the LES, rather than restoring or modifying the underlying pathology. new therapies should aim to stop the disease at early stages, thereby preventing the consequential changes from developing and inhibiting permanent damage. This review focuses on the known characteristics of idiopathic achalasia that will help promote understanding its pathogenesis and improve therapeutic management to positively impact the patient's quality of life.

关键词： Achalasia Treatment Autoimmune disease Pathophysiology

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Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort

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World Journal of Gastroenterology 2019年第4期25卷 433-446页

作者： Patricia Prieto Rafael I Jaén Daniel Calle María Gómez-Serrano Estefanía nú?ez María Fernández-Velasco Paloma martín-Sanz Sergio Alonso Jesús Vázquez Sebastián Cerdán miguel ángel Peinado Lisardo Boscá department of Metabolism and Physiopathology of Inflammatory Diseases Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (Ciber-CV) Instituto de Salud Carlos III (ISCIII) Laboratorio de Imagen Médica Hospital Universitario Gregorio Mara?ón Laboratorio de Proteómica Cardiovascular Centro Nacional de Investigaciones Cardiovasculares (CNIC) Instituto de Investigación Sanitaria del Hospital Universitario la Paz(IdiPaz) Programa de Medicina Predictiva y Personalizada del Cáncer (PMPPC) Fundación Instituto de investigación en ciencias de la salud Germans Trias i PujolCtra Can Ruti

BACKGROUnD Colorectal cancer(CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2(COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in *** To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic *** Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge(Barcelona, Spain) and Germans Trias i Pujol University Hospital(Campus Can Ruti)(Barcelona, Spain). Western blot analysis was used to determine COX-2 levels. deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide n-glycosidase F(PnGase F). Prostaglandin E2(PGE2) levels were determined using a specific ELISA. 1 H high resolution magic angle spinning(HRMAS) analysis was performed using a Bruker AVIII 500 MHz spectrometer and proteomic analysis was performed in a nano-liquid chromatography-tandem mass spectrometer(nano LC-MS/MS) using a QExactive HF orbitrap *** Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients vs the adjacent non-tumor area, which correspond to a glycosylated and less active state of the protein. This fact was associated to a lesser PGE2 production in tumors. These results were corroborated in vitro performing deglycosylation assays in HT29 cell line where COX-2 protein profile was modified after Pn

关键词： Colon Carcinoma Cyclooxygenase Prostaglandin Proteomics High resolution magic angle spinning

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Open versus laparoscopic cholecystectomies in patients with or without type 2 diabetes mellitus in Spain from 2003 to 2013

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Hepatobiliary & Pancreatic Diseases International 2016年第5期15卷 525-532页

作者： JoséM de miguel-Yanes Manuel Méndez-Bailón Rodrigo Jiménez-García Valentín Hernández-Barrera napoleón Pérez-Farinós Fernando Turégano nuria Munoz-Rivas Ana López-de-Andrés Internal Medicine department Hospital General Universitario“Gregorio Maranón”46Doctor Esquerdo28007MadridSpain Internal Medicine department Hospital Clínico San CarlosCalle Profesor Martín Lagos28040MadridSpain Preventive Medicine and Public Health department Health Sciences FacultyRey Juan Carlos UniversityAvenida de AtenasAlcorcón28292MadridSpain Spanish Agency of Alimentary Safety and nutrition Ministry of HealthSocial Policy and Equality56Alcalá28071MadridSpain Internal Medicine department Hospital Infanta Leonor80Avenida Gran Vía del Este28031MadridSpain Surgery department Hospital General Universitario“Gregorio Maranón”46Doctor Esquerdo28007MadridSpain

BACKGROUnD: This study aimed to compare the rates of open and laparoscopic cholecystectomies and outcomes in patients with or without type 2 diabetes mellitus (T2DM) in Spain from 2003 to 2013. METHODS: We collected all cases of open and laparoscopic cholecystectomies using national hospital discharge data and evaluated the annual cholecystectomy rates stratiifed by T2DM status. We analyzed tendency for in-hospital mortality (IHM). We also analyzed the impact of T2DM on IHM in patients who underwent cholecystectomies. RESULTS: We identiifed 611 533 cholecystectomies (71.3%laparoscopic) in the patients, in whom 78 227 (12.8%) patients had T2DM. The rates of open cholecystectomies were 3-fold higher (130.0/105 vs 41.1/105) in patients with T2DM than in those without T2DM, and the rate of laparoscopic cholecys-tectomies was almost 2-fold higher (195.2/105 vs 111.8/105) in patients with T2DM. The annual rate of laparoscopic pro-cedures showed an 11-year relative increase of 88.3% (from 117.0/105 to 220.3/105) in T2DM and 49.2% (from 79.2/105 to 118.2/105) in patients without T2DM (Pn procedures showed an 11-year relative decrease of 27.6% in patients with T2DM and 37.9% in those without T2DM (Pncy laparoscopic cho-lecystectomy was increased in the 11 years, whereas the rate of emergency open cholecystectomies was decreased (both Pnalysis revealed that older age, higher comorbidity and emergency cholecystectomy were associated with a higher IHM. Compared with patients without T2DM, patients with T2DM demonstrated a lower IHM after open cholecystectomy [OR=0.82 (0.78-0.87)], but a higher IHM after laparoscopic cholecystectomy (OR=1.18 (1.03-1.35))Time-trend analyses showed a signiifcant reduction in IHM in patients with or without T2DM after the two procedures. COnCLUSIOn: The rate of cholecystectomy was higher in patients with T2DM, and laparoscopic cholecystectomy was p

关键词： diabetes mellitus cholecystectomy mortality in-hospital mortality

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Translational pancreatic cancer research:a comparative study on patient-derived xenograft models

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World Journal of Gastroenterology 2018年第7期24卷 794-809页

作者： Mercedes Rubio-Manzanares Dorado Luis miguel Marín Gómez Daniel Aparicio Sánchez Sheila Pereira Arenas Juan Manuel Praena-Fernández Juan Jose Borrero martín Francisco Farfán López miguel ángel Gómez Bravo Jordi Muntané Relat Javier Padillo Ruiz department of Hepatobiliary and Pancreatic Surgery Virgen del Rocio University Hospital Oncology Surgery Cell Therapy and Organ Transplantation Group Institute of Biomedicine of Seville (IBiS) Virgen del Rocio University Hospital University of Seville Statistics Methodology and Evaluation of Research Unit Virgen del Rocio University Hospital Pathology department Virgen del Rocio University Hospital

AIM To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude *** This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations(intraperitoneal, subcutaneous and pancreatic). Histological analysis(haematoxylin-eosin and Masson's trichrome staining) and immunohistochemical assessment of apoptosis(TUnEL), proliferation(Ki-67), angiogenesis(CD31) and fibrogenesis(α-SMA) were performed. When a tumour xenograft reached the target size, it was reimplanted in a new nude mouse. Three sequential tumour xenograft generations were generated(F1, F2 and F3).RESULTS The overall tumour engraftment rate was 61.1%. The subcutaneous model was most effective in terms of tissue growth(69.9%), followed by intraperitoneal(57.6%) and pancreatic(55%) models. Tumour development was faster in the subcutaneous model(17.7 ± 2.6 wk) compared with the pancreatic(23.1 ± 2.3 wk) and intraperitoneal(25.0 ± 2.7 wk) models(P = 0.064). There was a progressive increase in the tumour engraftment rate over successive generations for all three models(F1 28.1% vs F2 71.4% vs F3 80.9%, P no significant differences in tumour xenograft differentiation and cell proliferation between human samples and the three experimental models among the sequential generations of tumour xenografts. However, a progressive decrease in fibrosis, fibrogenesis, tumour vascularisation and apoptosis was observed in the three experimental models compared with the human samples. All three pancreatic patient-derived xenograft models presented similar histological and immunohistochemical *** In our experie

关键词： Immunohistological analysis Pancreatic cancer Patient-derived xenograft Animal model nude mice

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Management of incidentally discovered appendiceal neuroendocrine tumors after an appendicectomy

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World Journal of Gastroenterology 2022年第13期28卷 1304-1314页

作者： JoséLuis Muñoz de nova Jorge Hernando miguel Sampedro núñez Greissy Tibisay Vázquez Benítez Eva María Triviño Ibáñez María Isabel del Olmo García Jorge Barriuso Jaume Capdevila Elena martín-Pérez department of General and Digestive Surgery Hospital Universitario de La PrincesaMadrid 28006Spain department of Surgery Universidad Autónomade MadridMadrid 28029Spain Gastrointestinal and Endocrine Tumor Unit Medical Oncology DepartmentVall d´Hebron University HospitalVall d´Hebron Institute of OncologyBarcelona 08035Spain department of Endocrinology and nutrition Hospital Universitario de La PrincesaMadrid 28006Spain department of Pathology Hospital Universitario Puerta de HierroMadrid 28222Spain department of Pathology Universidad Autónoma de MadridMadrid 28029Spain department of nuclear Medicine Virgen de las Nieves University HospitalGranada 18014Spain department of Endocrinology and nutrition Hospital Universitario i Politècnic La FeValencia 46023Spain Division of Cancer Sciences School of Medical SciencesFaculty of BiologyMedicine and HealthUniversity of ManchesterManchester M139PLUnited Kingdom department of Medical Oncology The Christie NHS Foundation TrustManchester M204BXUnited Kingdom

Appendiceal neuroendocrine tumors(anETs)are an uncommon neoplasm that is relatively indolent in most *** are typically diagnosed in younger patients than other neuroendocrine tumors and are often an incidental finding after an *** there are numerous clinical practice guidelines on management of a nETs,there is continues to be a dearth of evidence on optimal *** of these tumors is stratified according to risk of locoregional and distant ***,there is a lack of consensus regarding tumors that measure 1-2 *** these cases,some histopathological features such as size,tumor grade,presence of lymphovascular invasion,or mesoappendix infiltration must also be *** tomography or magnetic resonance imaging scans are recommended for evaluating the presence of additional disease,except in the case of tumors smaller than 1 cm without additional risk *** receptor scintigraphy or positron emission tomography with computed tomography should be considered in cases with suspected residual or distant *** main point of controversy is the indication for performing a completion right hemicolectomy after an initial appendectomy,based on the risk of lymph node *** main factor considered is tumor size and 2 cm is the most common threshold for indicating a *** factors such as mesoappendix infiltration,lymphovascular invasion,or tumor grade may also be *** the other hand,potential complications,and decreased quality of life after a hemicolectomy as well as the lack of evidence on benefits in terms of survival must be taken into *** this review,we present data regarding the current indications,outcomes,and benefits of a colectomy.

关键词： neuroendocrine tumors Carcinoid tumor Appendiceal neoplasms Colectomy neoplasm grading Treatment outcome

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Litter buffet:On the use of trash bins by birds in six boreal urban settlements

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Avian Research 2023年第2期14卷 182-190页

作者： Michelle García-Arroyo miguel A.Gomez-martínez Ian MacGregor-Fors Ecosystems and Environment Research Programme Faculty of Biological and Environmental SciencesUniversity of HelsinkiNiemenkatu 73Lahti15140Finland Instituto de Biotecnología y Ecología Aplicada(InBIOTECA) Universidad VeracruzanaXalapa91090Mexico

Unintentional food resources in urban areas(street litter,food leftovers,overflowing trash bins)are dietary components of some urban-exploiter bird *** this study,we report on 13 bird species in six southern Finnish cities using urban trash bins and describe differences in their activity when provided with food resources(i.e.,bait)in different bin *** used generalized linear models(GLM)and classification and regression trees(CART)to test for associations between environmental variables and bird activity at the *** activity at the binscapes significantly differed among all cities and among types of bins and was significantly higher after placing bait in all *** with the largest opening had more activity as opposed to those with smaller openings or *** and gulls had the highest activity,with corvids usually being present before the bait was placed and gulls increasing their activity *** differences show that trash bin foraging is highly malleable and thus susceptible to management preventing its *** waste management measures could aid in reducing the number of species close to bins and their surroundings,benefiting both bird and human health.

关键词： Avian Behavior Binscape Food resources Urban ecology

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West nile virus: A re-emerging pathogen revisited

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World Journal of Virology 2012年第2期1卷 51-70页

作者： miguel A martín-Acebes Juan-Carlos Saiz department of Biotechnology Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria 28040 Madrid Spain

West nile virus(WnV), a flavivirus of the Flaviviridae family, is maintained in nature in an enzootic transmission cycle between avian hosts and ornithophilic mosquito vectors, although the virus occasionally infects other vertebrates. WnV causes sporadic disease outbreaks in horses and humans, which may result in febrile illness, meningitis, encephalitis and flaccid paralysis. Until recently, its medical and veterinary health concern was relatively low; however, the number, frequency and severity of outbreaks with neurological consequences in humans and horses have lately increased in Europe and the Mediterranean basin. Since its introduction in the Americas, the virus spread across the continent with worrisome consequences in bird mortality and a considerable number of outbreaks among humans and horses, which have resulted in the largest epidemics of neuroinvasive WnV disease ever documented. Surprisingly, its incidence in human and animal health is very different in Central and South America, and the reasons for it are not yet understood. Even though great advances have been obtained lately regarding WnV infection, and although efficient equine vaccines are available, no specific treatments or vaccines for humanuse are on the market. This review updates the most recent investigations in different aspects of WnV life cycle: molecular virology, transmission dynamics, host range, clinical presentations, epidemiology, ecology, diagnosis, control, and prevention, and highlights some aspects that certainly require further research.

关键词： West nile virus Emerging pathogen Molecular biology Diagnosis Pathology Epidemiology Vaccines Antivirals

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Healthy diet,depression and quality of life:A narrative review of biological mechanisms and primary prevention opportunities

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World Journal of Psychiatry 2021年第11期11卷 997-1016页

作者： Octavio Pano Elena H martínez-Lapiscina Carmen Sayón-Orea miguel Angel martinez-Gonzalez Jose Alfredo martinez Almudena Sanchez-Villegas Preventive Medicine and Public Health University of NavarrePamplona 31008Spain department of neurology Center of neuroimmunology Hospital Clinic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi SunyerBarcelona 08036Spain department of Preventive Medicine and Public Health University of NavarraPamplona 31008Spain IdiSnA Navarra Institute for Health ResearchPamplona 31008Spain department of Public Health Navarra Institute of Public Health and EpidemiologyPamplona 31003Spain CIBER Pathophysiology of Obesity and nutrition Institute of Health Carlos IIIMadrid 28049Spain department of nutrition Harvard T.H.Chan School of Public HealthBostonMA 02115United States department of Food Sciences and Physiology University of NavarrePamplona 31008Spain Precision nutrition and Cardiometabolic Health Program IMDEA Food InstituteMadrid 28049Spain department of Clinical Sciences University of Las Palmas Gran CanariaLas Palmas Gran Canaria 35080Spain

Unipolar depressive disorder(UDD)affects more than 264 million people worldwide and was projected well before the severe acute respiratory syndrome coronavirus 2 pandemic to be the leading cause of disability-adjusted life years lost in *** is imperative for leading economies to implement preventive strategies targeted towards UDD,given consistent policies are currently *** established similarities between the aetiological hypotheses of depression and cardiometabolic diseases are shifting paradigms within this *** is believed that dietary practices could potentially reduce the incidence of depression;similar to their effects on ***,the aim of this review was to compile current evidence on healthy dietary patterns as suitable contributors towards primary prevention strategies against *** of the well-known biological mechanisms behind depression have been positively associated with healthful diets and dietary patterns to varying ***,a common factor of UDD is the production and overall effects of inflammatory cytokines,such as interleukin-6,tumor necrosis factor-α,and Creactive *** compounds have been associated with depressive symptoms,disturbances in neuroendocrine function,leaky gut,monoamine activity and brain function,while also being key factors in the development of cardiometabolic *** Mediterranean diet(MD)in particular,is well supported by first-level evidence regarding its preventive qualities against metabolic and cardiovascular diseases and thus considered a model for healthy eating by various *** one of the few clinical trials investigating these associations,the PREDIMED trial,individuals with diabetes assigned to a MD supplemented with mixed tree nuts experienced a 41%relative risk reduction for developing ***,there is a need to include health related quality of life as an indicator of physical and mental well-being,considering its putative associations

关键词： depression nutrition Mediterranean Quality of life Primary prevention Epidemiology

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Effect of transjugular intrahepatic portosystemic shunt on pulmonary gas exchange in patients with portal hypertension and hepatopulmonary syndrome

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World Journal of Gastroenterology 2005年第43期11卷 6858-6862页

作者： Graciela martínez-Pallí Britt B Drake Joan-Carles García-Pagán Joan-Albert Barberà miguel R Arguedas Robert Rodriguez-Roisin Jaume Bosch Michael B Fallon Servei d'Anestesiologia i Reanimació. Hospital Clínic University of Alabama at Birmingham Liver Center Hepatic Hemodynamic Laboratory Servei de Pneumologia i Al.lèrgia Respiratòria

AIM: To assess the impact of transjugular intrahepatic portosystemic shunt (TIPS) on pulmonary gas exchange and to evaluate the use of TIPS for the treatment of hepatopulmonary syndrome (HPS).METHODS: Seven patients, three of them with advanced HPS, in whom detailed pulmonary function tests were performed before and after TIPS placementat the University of Alabama Hospital and at the Hospital Clinic, Barcelona, were ***: TIPS patency was confirmed by hemodynamic evaluation. no changes in arterial blood gases were observed in the overall subset of patients. Transient arterial oxygenation improvement was observed in only one HPS patient, early after TIPS, but this was not sustained 4 mo ***: TIPS neither improved nor worsened pulmonary gas exchange in patients with portal hypertension. This data does not support the use of TIPS as a specific treatment for HPS. However, it does reinforce the view that TIPS can be safely performed for the treatment of other complications of portal hypertension in patients with HPS.

关键词： Portal hypertension Transjugular intrahepaticportosystemic shunt Pulmonary gas exchange Hepatopulmonary syndrome

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Mediterranean diet as the ideal model for preventing non-alcoholic fatty liver disease (nAFLD)

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Hepatobiliary Surgery and nutrition 2020年第3期9卷 379-381页

作者： miguel A.martínez-González Gorka Bastarrika Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la nutrición(CIBEROBn) Institute of Health CarlosⅢMadridSpain University of navarra Department of Preventive Medicine and Public HealthIDISNAPamplonaSpain department of nutrition Harvard T.H.Chan School of Public HealthBostonMAUSA University of navarra Department of RadiologyClínica Universidad de NavarraPamplonaSpain

The prevalence of nonalcoholic fatty liver disease(nAFLD)has dramatically increased in the 2–3 last decades and it represents the most frequent global cause of liver disease,affecting 25%to 45%of adults in most studi... 详细信息

关键词： nAFLD liver prevalence

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