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Genetic variables of the glutamatergic system associated with treatment-resistant depression:A review of the literature

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World Journal of Psychiatry 2022年第7期12卷 884-896页

作者： Estela Saez Leire Erkoreka Teresa Moreno-Calle Belen Berjano Ana Gonzalez-Pinto Nieves Basterreche Aurora Arrue Department of Psychiatry Barrualde-Galdakao Integrated Health OrganizationOsakidetza-Basque Health ServiceGaldakao 48960Spain Mental health Network Group Biocruces Bizkaia Health Research InstituteBarakaldo 48903Spain Department of Neurosciences University of the Basque Country UPV/EHULeioa 48940Spain Department of Psychiatry Araba Integrated Health OrganizationOsakidetza-Basque Health ServiceCIBERSAMVitoria-Gasteiz 01004Spain Severe Mental Disorders Group Bioaraba Health Research InstituteVitoria-Gasteiz 01009Spain Zamudio Hospital Bizkaia Mental Health NetworkOsakidetza-Basque Health ServiceZamudio 48170Spain Integrative research Group in Mental health Biocruces Bizkaia Health Research InstituteBarakaldo 48903Spain Neurochemical research Unit Bizkaia Mental Health NetworkOsakidetza-Basque Health ServiceBarakaldo 48903Spain

Depression is a common,recurrent mental disorder and one of the leading causes of disability and global burden of disease *** to 15%-40%of cases do not respond to diverse pharmacological treatments and,thus,can be defined as treatment-resistant depression(TRD).The development of biomarkers predictive of drug response could guide us towards personalized and earlier *** evidence points to the involvement of the glutamatergic system in the pathogenesis of ***,the N-methyl-D-aspartic acid receptor(NMDAR)andα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR),which are targeted by ketamine and esketamine,are proposed as promising pathways.A literature search was performed to identify studies on the genetics of the glutamatergic system in depression,focused on variables related to NMDARs and *** review highlights GRIN2B,which encodes the NR2B subunit of NMDAR,as a candidate gene in the pathogenesis of *** addition,several studies have associated genes encoding AMPAR subunits with symptomatic severity and suicidal *** genes encoding glutamatergic receptors could,therefore,be candidate genes for understanding the etiopathogenesis of TRD,as well as for understanding the pharmacodynamic mechanisms and response to ketamine and esketamine treatment.

关键词： Genetics N-methyl-D-aspartic acid receptor α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor Treatment-resistant depression Ketamine Esketamine

Genetics of adult attachment:An updated review of the literature

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World Journal of Psychiatry 2021年第9期11卷 530-542页

作者： Leire Erkoreka Mercedes Zumarraga Aurora Arrue M Isabel Zamalloa Ainara Arnaiz Olga Olivas Teresa Moreno-Calle Estela Saez Jon Garcia Elena Marin Noemi Varela Ana Gonzalez-Pinto Nieves Basterreche Department of Psychiatry Galdakao-Usansolo HospitalOsakidetza Basque Health ServiceGaldakao 48960Spain Grupo Red de Salud Mental Biocruces Bizkaia Health Research InstituteBarakaldo 48903Spain Department of Neurosciences University of the Basque Country UPV/EHULeioa 48940Spain Department of Neurochemical research Bizkaia Mental Health NetworkOsakidetza Basque Health ServiceBarakaldo 48903Spain Erandio Mental health Center Bizkaia Mental Health NetworkOsakidetza Basque Health ServiceErandio 48950Spain Zaldibar Hospital Bizkaia Mental Health NetworkOsakidetza Basque Health ServiceZaldibar 48250Spain Zamudio Hospital Bizkaia Mental Health NetworkOsakidetza Basque Health ServiceZamudio 48170Spain Bermeo Hospital Bizkaia Mental Health NetworkOsakidetza Basque Health ServiceBermeo 48370Spain Department of Psychiatry BioAraba Research InstituteAraba University HospitalUniversity of the Basque Country(UPV/EHU)CIBERSAMVitoria-Gasteiz 01004Spain Grupo de investigacion integradora en Salud Mental Biocruces Bizkaia Health Research InstituteBarakaldo 48903Spain

Attachment style,which has been theorized to be rooted in childhood bonding experiences,influences adult cognitive,emotional and interpersonal *** its relationship with early experiences,research indicates that the continuity of attachment style across childhood and adulthood is only partial,being a malleable tendency that is shaped throughout development,with an increasing influence of genetics,as it occurs in other cognitive and behavioral *** research indicates that up to 45% of the variability in anxious and 39% in avoidant adult attachment style could be explained by genetic causes,but the precise mechanisms remain unclear.A narrative review is conducted analyzing the existing literature regarding the implication of candidate genes related to oxytocin,dopaminergic pathways,serotonergic pathways and brainderived neurotrophic factor in adult attachment,with both vulnerability and differential susceptibility approaches,yielding mixed *** highlight the lack of genome-wide studies and the scarcity of epigenetic *** on the existing data,we conclude that the genetics of adult attachment is an area that requires further research to clarify its etiological role and that it should be preferably approached as an interaction between nature and nurture.

关键词： Genetics Adult attachment Oxytocin Dopamine Serotonin Brain-derived neurotrophic factor Methylation

m6A levels and expression of its modification genes show significant differences in breast cancer molecular subtypes

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Genes & Diseases 2023年第5期10卷 1751-1754页

作者： Tamara Kleinbielen Felix Olasagasti Elena Beristain Amparo Viguri-Díaz Isabel Guerra-Merino Africa García-Orad Marian Mde Pancorbo BIOMICs research Group Lascaray Research CenterUniversity of the Basque Country UPV/EHUVitoria-GasteizAraba 01006Spain Bioaraba health research institute Vitoria-GasteizAraba 01009Spain Department of Biochemistry and Molecular Biology University of the Basque CountryUPV/EHUVitoria-GasteizAraba 01006Spain Molecular Genetics Laboratory Araba University HospitalOsakidetza Basque Health ServiceVitoria-GasteizAraba 01009Spain Pathology Department Araba University HospitalVitoria-GasteizAraba 01009Spain Department of Genetics Physical Anthropology and Animal PhysiologyUniversity of the Basque Country(UPV/EHU)LeioaBizkaia 48940Spain biocruces bizkaia health research institute BarakaldoBizkaia 48903Spain Department of Zoology and Animal Biology.University of the Basque Country(UPV/EHU) LeioaBizkaia 48940Spain

N6-methyladenosine(m6A)is the most abundant modification in eukaryotic messenger RNA.1 This modification is dynamic,reversible,and mediated by proteins characterized as methyltransferases and *** investigations have found that aberrant expression of methyltransferases and demethylases results in m6A dysregulation and,in consequence,affects the biological functions in which this modification is ***,m6A dysregulation affects the development and maintenance of various diseases,including cancer.2 For this reason,we explored the potential role that m6A modification has in invasive breast cancer of no special type(IBC-NST)and its molecular subtypes luminal A,luminal B HER2-,luminal B HER2+,HER2+,and triple-negative breast cancer(TNBC)whose degree of global m6A methylation has not yet been studied.

关键词： breast cancer HER2

Endovascular treatment for early hepatic artery occlusion after liver transplantation: Angioplasty or stent

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Hepatobiliary & Pancreatic Diseases International 2022年第6期21卷 614-615页

作者： Mikel Gastaca Javier Gomez Ignacio Terreros Hepatobiliary Surgery and Liver Transplantation Unit Biocruces Bizkaia Health Research InstituteHospital Universitario CrucesBilbaoSpain University of the Basque Country BilbaoSpain Servicio de Cirugía General y Aparato Digestivo Hospital Universitario San CecilioGranadaSpain Interventional Radiology Unit Hospital Universitario CrucesBilbaoSpain

To the Editor:We read with great interest the recent article by Zhu et al.[1].In the study,the authors analyzed the outcomes of 26 patients diagnosed with hepatic artery occlusion(HAO)and treated with an endovascular approach(EVT)within the first 30 days after ortho-topic liver transplantation(LT).The median interval from LT to EVT was 7 days,most patients were treated with angioplasty and only two(7.7%)needed stent *** authors should be congrat-ulated as they achieved a 100%of success rate with an 80.8%of 1-year survival rate.

关键词： liver artery after

Early tacrolimus exposure does not impact long-term outcomes after liver transplantation

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World Journal of Hepatology 2021年第3期13卷 362-374页

作者： Mikel Gastaca Patricia Ruiz Javier Bustamante Lorea Martinez-Indart Alberto Ventoso JoséRamón Fernandez Ibone Palomares Mikel Prieto Milagros Testillano Patricia Salvador Maria Senosiain Maria Jesus Suárez Andres Valdivieso Department of HPB Surgery and Liver Transplantation Unit Hospital Universitario CrucesBilbao 48903Spain Department of Hepatology Unit Hospital Universitario CrucesBilbao 48903Spain Department of Bioinformatics and Statistics Platform Biocruces Bizkaia Health Research InstituteHospital Universitario CrucesBilbao 48903Spain

BACKGROUND Tacrolimus trough levels(TTL)during the first weeks after liver transplantation(LT)have been related with long-term renal function and hepatocellular carcinoma ***,the significance of trough levels of tacrolimus during the early post-transplant period for the long-term outcome is under debate AIM To evaluate the effect of TTL during the first month on the long-term outcomes after *** One hundred fifty-five LT recipients treated de novo with once-daily tacrolimus were retrospectively *** with repeated LT or combined transplantation were excluded as well as those who presented renal dysfunction prior to transplantation and/or those who needed induction *** were classified into 2 groups according to their mean TTL within the first month after transplantation:≤10(n=98)and>10 ng/mL(n=57).Multivariate analyses were performed to assess risk factors for patient *** Mean levels within the first month post-transplant were 7.4±1.7 and 12.6±2.2 ng/mL in the≤10 and>10 groups,*** age was higher in the high TTL group 62.9±16.8 years vs 45.7±17.5 years(P=0.002)whilst mycophenolate-mofetil was more frequently used in the low TTL group 32.7%vs 15.8%(P=0.02).Recipient features were generally similar across *** a median follow-up of 52.8 mo(range 2.8-81.1),no significant differences were observed in:Mean estimated glomerular filtration rate(P=0.69),hepatocellular carcinoma recurrence(P=0.44),de novo tumors(P=0.77),new-onset diabetes(P=0.13),or biopsy-proven acute rejection rate(12.2%and 8.8%,respectively;P=0.50).Eighteen patients died during the follow-up and were evenly distributed across groups(P=0.83).Five-year patient survival was 90.5%and 84.9%,respectively(P=0.44),while 5-year graft survival was 88.2%and 80.8%,respectively(P=0.42).Early TTL was not an independent factor for patient mortality in multivariate *** Differences in tacrolimus levels restricted to the fi

关键词： Liver transplantation Tacrolimus levels Prolonged released tacrolimus Oncedaily tacrolimus Renal function Survival Outcomes

Environmental pollution with psychiatric drugs

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World Journal of Psychiatry 2021年第10期11卷 791-804页

作者： Julene Argaluza Saioa Domingo-Echaburu Gorka Orive Juan Medrano Rafael Hernandez Unax Lertxundi Department of Epidemiology and Public health Bioaraba Health Research InstituteVitoria-Gasteiz 01002Spain Department of Pharmacy Alto Deba Integrated Health Care OrganizationArrasate 20500Spain NanoBioCel Group Laboratory of PharmaceuticsSchool of PharmacyUniversity of the Basque Country UPV/EHUPaseo de la Universidad 7Vitoria-Gasteiz 01006Spain Biomedical research Networking Centre in Bioengineering Biomaterials and Nanomedicine(CIBER-BBN)Vitoria-Gasteiz 01006Spain Bioaraba NanoBioCel Research GroupVitoria-Gasteiz 01006Spain Singapore Eye research institute Discovery TowerSingapore 168751Singapore Department of Psychiatry Biocruces Bizkaia Health Research InstituteMental Health Network Research GroupOsakidetzaPortugalete 48920Spain Department of Internal Medicine Araba Mental Health NetworkVitoria-Gasteiz 01006Spain Bioaraba health research institute/Osakidetza Basque health Service Araba Mental Health NetworkAraba Psychiatric HospitalPharmacy ServiceVitoria-Gasteiz 01006AlavaSpain

Among all contaminants of emerging interest,drugs are the ones that give rise to the greatest *** of the multiple stages of the drug's life cycle(production,consumption and waste management)is a possible entry point to the different environmental *** drugs have received special attention because of two ***,their use is ***,many of them act on phylogenetically highly conserved neuroendocrine systems,so they have the potential to affect many non-target ***,wastewater is considered the most important source of drugs to the ***,the currently available wastewater treatment plants are not specifically prepared to remove drugs,so they reach practically all environmental matrices,even tap *** drugs are designed to produce pharmacological effects at low concentrations,they are capable of producing ecotoxicological effects on microorganisms,flora and fauna,even on human *** has also been observed that certain antidepressants and antipsychotics can bioaccumulate along the food *** pollution is a complicated and diffuse problem characterized by scientific uncertainties,a large number of stakeholders with different values and interests,and enormous *** solutions consist on acting at source,using medicines more rationally,eco-prescribing or prescribing greener drugs,designing pharmaceuticals that are more readily biodegraded,educating both health professionals and citizens,and improving coordination and collaboration between environmental and healthcare ***,end of pipe measures like improving or developing new purification systems(biological,physical,chemical,combination)that eliminate these residues efficiently and at a sustainable cost should be a ***,we describe and discuss the main aspects of drug pollution,highlighting the specific issues of psychiatric drugs.

关键词： Antipsychotics Pharmaceuticals in the environment Drug pollution Antidepressants Wastewater Ecotoxicity

Control of APN/CD13 and NEP/CD10 on sperm motility

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Asian Journal of Andrology 2010年第6期12卷 899-902页

作者： Nerea Subiran Francisco M. Pinto Ekaitz Agirregoitia Luz Candenas Jon Irazusta Department of Physiology Faculty of Medicine and Dentistry University of the Basque Country Leioa Bizkaia 48940 Spain Chemical research institute - CSiC University of Seville Seville 41092 Spain

Aminopeptidase N （APN/CD13） and neutral endopeptidase （NEP/CD10） are enzymes present in human sperm cells and involved in regulation of sperm motility of noncapacitated spermatozoa. We investigated the involvement of APN/CD 13 and NEP/CD 10 in motility and in kinematic parameters of human capacitated spermatozoa. Sperm cells isolated by a discontinuous Percoll gradient （40%-80%） followed up by swim-up techniques were incubated with the APN/CD 13 -specific inhibitor, leuhistin （100 μmol L^-1）, and the NEP/CD 10-specific inhibitor, thiorphan （1 μmol L^-1）. The complete inhibition of both APN/CD 13 and NEP/CD 10 improved sperm motility. Spermatozoa incubated with the APN/CD13-specific inhibitor lenhistin showed asymmetrical trajectories, whereas sperm trajectories were more regular after treatment with the NEP/CD 10-specific inhibitor thiorphan. In conclusion, APN/CD 13 and NEP/CD 10 modulate the motility of capacitated spermatozoa, although each of the enzymes seems to participate in the control of different aspects of sperm motility. Therefore, both inhibitors may be useful for sperm activation at different functional stages of spermatozoa.

关键词： APN/CD13 human hypcractivation kinematic motility NEP/CD10 sperm

Colorectal and interval cancers of the Colorectal Cancer Screening Program in the Basque Country (Spain)

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World Journal of Gastroenterology 2017年第15期23卷 2731-2742页

作者： Isabel Portillo Eunate Arana-Arri Isabel Idigoras Isabel Bilbao Lorea Martínez-Indart Luis Bujanda Inaki Gutierrez-Ibarluzea biocruces health research institute Colorectal Cancer Screening Programme OsakidetzaBasque Health Service Department of Gastroenterology Hospital Donostia/Instituto BiodonostiaCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasUniversidad del País Vasco(UPV/EHU Basque Office for health Technology Assessment Ministry for HealthBasque Government

AIM To assess proportions, related conditions and survival of interval cancer(IC).METHODS The programme has a linkage with different clinical databases and cancer registers to allow suitable evaluation. This evaluation involves the detection of ICs after a negative faecal inmunochemical test(FIT), interval cancer FIT(IC-FIT) prior to a subsequent invitation, and the detection of ICs after a positive FIT and confirmatory diagnosis without colorectal cancer(CRC) detected and before the following recommended c o l o n o s c o p y, I C-c o l o n o s c o p y. W e c o n d u c t e d a retrospective observational study analyzing from January 2009 to December 2015 1193602 invited people onto the Programme(participation rate of 68.6%).RESULTS Two thousand five hundred and eighteen cancers were diagnosed through the programme, 18 cases of IC-colonoscopy were found before the recommended follow-up(43542 colonoscopies performed) and 186 IC-FIT were identified before the following invitation of the 769200 negative FITs. There was no statistically significant relation between the predictor variables of ICs with sex, age and deprivation index, but there was relation between location and stage. Additionally, it was observed that there was less risk when the location was distal rather than proximal(OR = 0.28, 95%CI: 0.20-0.40, P < 0.0001), with no statistical significance when the location was in the rectum as opposed to proximal. When comparing the screen-detected cancers(SCs) with ICs, significant differences in survival were found(P < 0.001); being the 5-years survival for SCs 91.6% and IC-FIT 77.8%.CONCLUSION These findings in a Population Based CRC Screening Programme indicate the need of population-based studies that continue analyzing related factors to improve their detection and reducing harm.

关键词： Colorectal cancer Population Screening Programme Interval cancer Faecal immunochemical test Colonoscopy Diagnosis Mortality Survival

CD300a inhibits CD16-mediated NK cell effector functions in HIV-1-infected patients

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Cellular & Molecular Immunology 2019年第12期16卷 940-942页

作者： Joana Vitallé Iñigo Terrén Ane Orrantia Raquel Pérez-Garay Francesc Vidal JoséA.Iribarren Carmen Rodríguez Ana M.López Lirola Enrique Bernal Olatz Zenarruzabeitia Francisco Borrego Immunopathology Group Biocruces Bizkaia Health Research InstituteBarakaldoSpain Hospital Universitari de Tarragona Joan XXIII IISPVUniversitat Rovira i VirgiliTarragonaSpain Servicio de Enfermedades Infecciosas Hospital Universitario DonostiaInstituto de Investigación Sanitaria BiodonostiaDonostia-San SebastiánSpain Centro Sanitario Sandoval Hospital Clínico San CarlosInstituto de Investigación Sanitaria San CarlosMadridSpain Hospital Universitario de Canarias Santa Cruz de TenerifeSpain Department of Clinical Medicine Universidad de Murcia and Hospital General Universitario Reina SofíaMurciaSpain Ikerbasque Basque Foundation for ScienceBilbaoSpain

Natural killer(NK)cell-mediated antibody-dependent cellular cytotoxicity(ADCC)through CD16 plays a critical role in antihuman immunodeficiency virus(HIV)responses.1–3 CD300a is a surface receptor highly expressed on NK cells that has the capacity to inhibit NK cell-mediated cytotoxicity in healthy donors.4 The CD300a molecule has been related to several viral infections and is able to diminish the NK cell killing of pseudorabies-infected cells through interactions with its ligands phosphatidylserine and phosphatidylethanolamine.5 In addition,CD300a expression on B and CD4+T lymphocytes is altered during HIV-1 infection,and combined antiretroviral therapy(cART)does not restore nonpathological expression levels.5,6 However,the expression and function of CD300a on NK cells during HIV-1 infection is still *** have determined the surface expression of CD300a on different NK cell subsets and the capacity of this receptor to inhibit CD16-induced NK cell effector functions in healthy and HIV-1 infected individuals.

关键词： CD16 CD30 ADCC