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High Frequency of Antiviral Resistance Mutations in HBV Genotypes A2 and H: Multidrug Resistance Strains in Mexico

journal of Clinical and Translational Hepatology 2023年第5期11卷 1023-1034页

作者： Alexis jose-Abrego Sonia Roman joão renato rebello pinho Michele Soares Gomes-Gouvêa Arturo Panduro Department of Genomic Medicine in Hepatology Civil Hospital of Guadalajara“Fray Antonio Alcalde”GuadalajaraJaliscoMexico Health Sciences Center University of GuadalajaraGuadalajaraJaliscoMexico LIM07 Department of GastroenterologyUniversity of São PauloSão PauloBrazil Hospital Israelita Albert Einstein São PauloBrazil

Background and Aims:Lamivudine(3TC),telbivudine(LdT),entecavir(ETV),adefovir(ADF),and tenofovir(TFV)are drugs used to treat hepatitis B virus(HBV)infection,but specific mutations allow some viruses to become resistant to antiviral drugs or to acquire immune escape *** mutations have not been thoroughly investigated in *** study aimed to estimate the prevalence of HBV antiviral resistance and escape ***:This cross-sectional study analyzed 158 *** DNA was extracted,amplified,and sequenced in serum samples using the spin column method,PCR assay,and Sanger’s sequencing,*** genotypes were determined,and HBV mutations were tested using the Geno2pheno ***:overall,68.4%(108/158)of HBV patients were infected with genotype H,followed by G(11.4%,18/158),A2(10.8%,17/158),F1b(6.9.0%,11/158),D(1.9%,3/158),and E(0.6%,1/158),and 5.1%(8/158)had evidence of *** prevalence of resistance mutations was 8.2%(13/158)and the most common combined mutation was rt180M+***,we found the combinations rt180M+rt204V+rt173L(n=2)and rt180M+rt204V+rt202G(n=1)that confer multidrug resistance to 3TC,LdT,and *** mutations were found in genotypes A2(11.8%,2/17),and H(10.2%,11/108),and escape mutations were detected in HBV genotypes A2(11.8%,2/17),H(10.2%,11/108),F1b(9.1%,1/11)and G(5.6%,1/18).Conclusions:The highest prevalence of antiviral resistance mutations or escape mutations was detected in HBV genotypes A2 and *** earliest cases of HBV multidrug resistance were detected in Mexico.

关键词： Hepatitis B virus Drug resistance mutations Multidrug resistance strain Immune escape

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Differences in viral kinetics between genotypes 1 and 3 of hepatitis C virus and between cirrhotic and non-cirrhotic patients during antiviral therapy

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World journal of Gastroenterology 2006年第45期12卷 7271-7277页

作者： josé Eymard Medeiros-Filho Isabel Maria Vicente Guedes de Carvalho Mello joo renato rebello pinho Avidan U Neumann Fernanda de Mello Malta Luiz Caetano da Silva Flair josé Carrilho Hepatology Branch Department of Gastroenterology University of So Paulo School of Medicine So Paulo Brazil Viral Immu-nology Laboratory Instituto Butantan So Paulo Brazil Hepatology Branch Department of Gastroenterology University of S?o Paulo School of Medicine So Paulo Brazil Faculty of Life Sciences Bar-Ilan Univer-sity Ramat-Gan Israel Virology Branch Instituto Adolfo Lutz So Paulo Brazil

AIM: To evaluate the impact of hepatitis C virus (HCV) infection with genotype 1 or 3 and the presence or absence of liver cirrhosis (LC) in the early viral kinetics response to treatment. METHoDS: Naive patients (n = 46) treated with interferon-α (IFN-α) and ribavirin and followed up with frequent early HCV-RNA determinations were analysed. Patients were infected with genotype 1 (n = 28, 7 with LC) or 3 (n = 18, 5 with LC). RESULTS: The fi rst phase decline was larger in geno- type 3 patients than in genotype 1 patients (1.72 vs 0.95 log IU/mL, P ond phase slope decline was also larger in genotype 3 patients than in genotype 1 patients (0.87 vs 0.15 log/wk, P ound in both cirrhotic and non-cirrhotic patients. Genotype 1 cirrhotic patients had a slower 2nd phase slope than non-cirrhotic patients (0.06 vs 0.18 log/wk, P one of genotype 1 cirrhotic patients had a 1st phase decline larger than 1 log (non-cirrhotic patients: 55%, P oward a slower 2nd phase slope was observed in genotype 3 cirrhotic pa- tients but the 1st phase slope decline was not different. Sustained viral response was higher in genotype 3 pa- tients than in genotype 1 patients (72% vs 14%, P otype 1 non-cirrhotic patients than in genotype 1 cirrhotic patients (19% vs 0%). A secondphase decline slower than 0.3 log/wk was predictive of non-response in all groups. CoNCLUSIoN: Genotype 3 has faster early viral decline than genotype 1. Cirrhosis correlates with a slower 2nd phase decline and possibly with a lower 1st phase slope decline in genotype 1 patients.

关键词：肝炎病毒治疗方法肝硬化遗传型

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Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity

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Cellular & Molecular Immunology 2023年第8期20卷 955-968页

作者： Manuel M.Vicente Inês Alves Ângela Fernandes Ana M.Dias Beatriz Santos-Pereira Elena Pérez-Anton Sofia Santos Tao Yang Alexandra Correia Anja Münster-Kühnel Afonso R.M.Almeida Sarina Ravens Gabriel A.Rabinovich Manuel Vilanova Ana E.Sousa SaloméS.pinho i3S–Institute for Research and Innovation in Health University of PortoPortoPortugal Institute of Biomedical Sciences Abel Salazar(ICBAS) University of PortoPortoPortugal Graduate Program in Areas of Basic and Applied Biology(GABBA) ICBASUniversity of PortoPortoPortugal Faculty of Medicine University of PortoPortoPortugal Nephrology Department Centro Hospitalar e Universitário do PortoPortoPortugal Institute of Immunology Hannover Medical SchoolHannoverGermany Institute of Clinical Biochemistry Hannover Medical SchoolHannoverGermany Instituto de Medicina Molecular joão Lobo Antunes Faculdade de MedicinaUniversidade de LisboaLisboaPortugal Laboratorio de Inmunopatología Instituto de Biología y Medicina Experimental(IBYME)Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET)Ciudad de Buenos AiresArgentina Laboratorio de Inmuno-oncología Translacional Instituto de Biología y Medicina Experimental(IBYME)Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET)Ciudad de Buenos AiresArgentina Facultad de Ciencias Exactas y Naturales(FCEyN) Universidad de Buenos AiresCiudad de Buenos AiresArgentina

T-cell development ensures the formation of diverse repertoires of T-cell receptors(TCRs)that recognize a variety of *** is a major posttranslational modification present in virtually all cells,including T-lymphocytes,that regulates activity/*** these structures are known to be involved in TCR-selection in DP thymocytes,it is unclear how glycans regulate other thymic development processes and how they influence susceptibility to ***,we discovered stage-specific glycome compositions during T-cell development in human and murine thymocytes,as well as dynamic *** restricting the N-glycosylation profile of thymocytes to high-mannose structures,using specific glycoengineered mice(Rag1CreMgat1fl/fl),we showed remarkable defects in key developmental checkpoints,includingß-selection,regulatory T-cell generation andγδT-cell development,associated with increased susceptibility to colon and kidney inflammation and *** further demonstrated that a single N-glycan antenna(modeled in Rag1CreMgat2fl/fl mice)is the sine-qua-non condition to ensure normal *** conclusion,we revealed that mannosylated thymocytes lead to a dysregulation in T-cell development that is associated with inflammation susceptibility.

关键词： N-glycosylation T-cell development Thymocytes Glycocalyx Inflammation

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Microalbuminuria and Kidney Disease Risk in HIV Patients Taking Combined Antiretroviral Therapy

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World journal of AIDS 2014年第2期4卷 242-248页

作者： Huylmer Lucena Chaves Mayanna pinho Batista Adriana de Menezes Gomes Amanda Antunes Costa André Tigre Lima Vinícius Diniz Arcelino do Ceará Pedro Rubens Araújo Carvalho Linna Albuquerque Sampaio Fabrício de Maicy Bezerra Melissa Soares Medeiros Medicine School Unichristus Fortaleza Brazil

objectives: This study proposes to evaluate risk factors for kidney disease in HIV patients treated chronically and correlate with microalbuminuria measurements. Methods: Review charts and analyses of microalbuminuria in subgroup of HIV patients treated at Ceara/Brazil. Results: 149 patients, 69.1% male, mean 38.5 years old, infection mean 86.8 months. Mean Creatinine Clearance 110.2%, Creatinine 0.97, Urea 27.76 mg/dl, CD4+ 600.37 cels/mm3 and detectable viral load 530.59 copies with 61.7% undetectable. Mean Dosages of microalbuminuria/24h 147, 46 ± 820, 45 (N = 48) and microalbuminuria (mg/dl) 32.05 ± 85.25 (N = 43). Kidney Diseases Classification analyses evidenced 6.4% patients in stages ≥3 and 6.2% presented altered Microalbuminuria/24h. Patients using Tenofovir (TDF) 27.27% had Stage 2 and protease inhibitors (PI) had 4.1% in Stage 3. Proteinuria was observed in 5% stage ≥3. Association PI/TDF had 4.1% in Stage 3. No statistical difference between CD4 > or 3 and microalbuminuria/24h > 300 mg (p = 0.69);detectable/undetectable viral load and microalbuminuria/24h (p = 0.63) or stage ≥3 (p = 0.17);relation to Diabetes or arterial hypertension and microalbuminuria 24 h (p = 0.5 and p = 0.21);relation stage ≥3 and microalbuminuria/24h (p = 0.33);relation HIV diagnoses >/onths and stage ≥3 (p = 0.51);or microalbuminuria/24h and TDF (p = 0.4), PI (p = 1), TDF/PI (p = 0.69), Atazanavir (p = 0.4) or Lopinavir/r (p = 1) regimens. There was statistical significance comparing age > or or oalbuminuria/24h (p = 0.55) or microalbuminuria mg/d (p = 0.32). Relating comorbidities risk (Diabetes Mellitus plus Systemic Arterial Hypertension) to Kidney Diseases, it was found that 55.5% patients in Stage 3 or above with comorbidities compared with 15% with comorbidities in lower stages (P = 0.005). Nevertheless, comorbidities presence was not associated with microalbuminuria (p = 0.08). Conclusion: Kidney disease is a real risk for HIV patients and stages ≥

关键词： HIV AIDS Antiretroviral Kidney Disease Microalbuminuria

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Interleukin 28B-related polymorphisms: A pathway for understanding hepatitis C virus infection?

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World journal of Gastroenterology 2013年第42期19卷 7399-7404页

作者： Raquel Francine Liermann Garcia Simone Moreira Ana Lucia de Araújo Ramos Leslie Ecker Ferreira Angelo Alves de Mattos Cristiane Valle Tovo Lysandro Alsina Nader Juliene Antonio Ramos Edson Rondinelli Arnaldo de Jesus Dominici Christian Evangelista Garcia Mauro de Souza Leite pinho Carlos Eduardo Brando-Mello Cristiane Alves Villela-Nogueira Paulo Henrique Condeixa de Frana Departamento de Medicina Universidade da Regio de Joinville/UnivilleJoinville89219-719 Santa CatarinaBrazil Departamento de Clinica Médica e Cirurgia Geral Hospital Municipal So josé Joinville89202-000 Santa CatarinaBrazil Departamento de Clínica Médica Servio de HepatologiaFaculdade de Medicina/Hospital Universitário Clementino Fraga Filho/Universidade Federal do Rio de Janeiro21941-913 Rio de JaneiroBrazil Servio de Gastroenterologia e Hepatologia Irmandade da Santa Casa de Misericórdia/ISCMPAPorto Alegre90020-090 Rio Grande do SulBrazil Servio de Endoscopia Universidade Federal de Pelotas/UFPelPelotas96010-610 Rio Grande do SulBrazil Instituto de Biofísica Carlos Chagas Filho/UFRJ 21941-902 Rio de JaneiroBrazil Departamento de Gastroenterologia Hospital Universitário da Universidade Federal do Maranh o/UFMASo Luis65020-560 MaranhoBrazil Servio de Gastroenterologia Hospital Universitário Gaffrée Guinle/HUGG/UNIRIO20270-004 Rio de JaneiroBrazil

AIM:To analyze the role of rs12979860 and rs8099917polymorphisms in hepatitis C virus(HCV)genotype 1infection of ***:A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C(CHC)who had completed a 48-wk regimen of pegylated-interferonα-2a or-2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and199 healthy blood donors(controls)from a single site between January 2010 and January *** on the patients’response to treatment was *** chain reaction-restriction fragment length polymorphism genotyping of the interleukin(IL)28B gene fragment encompassing the single nucleotide polymorphisms(SNPs)rs12979860(C/T)and rs8099917(T/G)was carried out for 79 of the CHC patients and 199 of the ***-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC ***:SNP rs12979860 genotyping was successful in 99.5%of the controls and 97.2%of the CHC patients,whereas the SNP rs8099917 genotyping was successful in 95.5%of the controls and 100%of the CHC *** genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups,with significantly higher genotype frequencies of CC and TT in the controls(P=0.037 and 0.046,respectively)and of TT and GG in the CHC patients(P=0.0009and 0.0001,respectively).Analysis of the CHC patients who achieved sustained virological response(SVR)to treatment(n=55)indicated that the rs12979860 C allele and CC genotype were predictors of SVR(P=0.02).No significant correlation was found between rs8099917 genotypes and treatment response,but carriers of the T allele showed significantly higher rates of SVR(P=0.02).Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917(P=0.07).CoNCLUSIoN:The higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCVinfec

关键词： Hepatitis C Interleukin 28B Single nucleotide polymorphisms Sustained virological response Brazil

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CXCL9 and CXCL10 display an agedependent profile in Chagas patients:a cohort study of aging in Bambui,Brazil

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Infectious Diseases of Poverty 2020年第3期9卷 132-132页

作者： Fernanda Fortes de Araújo Karen Cecília Lima Torres Sérgio Viana Peixoto Antonio Luiz pinho Ribeiro Juliana Vaz Melo Mambrini Vitor Bortolo Rezende Maria Luiza Lima Silva Antônio Ignácio Loyola Filho Andréa Teixeira-Carvalho Maria Fernanda Lima-Costa olindo Assis Martins-Filho Integrated Research Group in Biomarkers Rene Rachou InstituteOswaldo Cruz FoundationAvenida Augusto de Lima1715–Barro Preto–Belo HorizonteMinas Gerais 30190-002Brazil 不详

Background:Chagas disease is endemic in Latin America and still represents an important public health problem in the *** cardiomyopathy is the most significant chronic form due to its association with morbidity and *** last decade has seen increasing evidence that inflammatory cytokines and chemokines are responsible for the generation of inflammatory infiltrate and tissue damage,with chronic chagasic cardiomyopathy patients presenting a pro-inflammatory immune *** studies have evaluated the role of chemokines in experimental *** infection,few have addressed their systemic profile,especially for human infection and in aging *** present work aimed to use the data from a large population based study of older adults,conducted in an endemic area for Chagas disease,to examine the association between serum levels of cytokines and chemokines,*** infection and electrocardiogram(ECG)***:The present work evaluated serum levels of CCL2,CXCL9,CXCL10,CCL5,CXCL8,IL-1β,IL-6,TNF,IL-12 and IL-10 by Flow Cytometric Bead Array assay(CBA)and the results expressed in pg/*** baseline survey started in January 1st 1997,with 1284 participants of an aged population-based *** signed an informed consent at baseline and at each subsequent visit and authorized death certificate and medical records ***:our results demonstrated that Chagas disease patients had higher serum levels of CXCL9,CXCL10 and IL-1βand lower serum levels of CCL5 than non-infected ***,our data demonstrated that CXCL9 and CXCL10 increased in an age-dependent profile in Chagas disease ***:Together,this study provided evidences that serum biomarkers increase along the age continuum and may have potential implications for establishing clinical management protocols and therapeutic intervention in Chagas disease patients.

关键词： Chagas disease Immune biomarkers Chemokines Cytokines Cohort

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Decline in subarachnoid haemorrhage volumes associated with the first wave of the CoVID- 19 pandemic

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Stroke & Vascular Neurology 2021年第4期6卷 542-552,I0026-I0032页

作者： Thanh N Nguyen Diogo C Haussen Muhammad M Qureshi Hiroshi Yamagami Toshiyuki Fujinaka ossama Y Mansour Mohamad Abdalkader Michael Frankel Zhongming Qiu Allan Taylor Pedro Lylyk omer F Eker Laura Mechtouff Michel Piotin Fabricio oliveira Lima Francisco Mont'Alverne Wazim Izzath Nobuyuki Sakai Mahmoud Mohammaden Alhamza R Al-Bayati Leonardo Renieri Salvatore Mangiafico David ozretic Vanessa Chalumeau Saima Ahmad Umair Rashid Syed Irteza Hussain Seby john Emma Griffin john Thornton jose Antonio Fiorot Rodrigo Rivera Nadia Hammami Anna M Cervantes-Arslanian Hormuzdiyar H Dasenbrock Huynh Le Vu Viet Quy Nguyen Steven Hetts Romain Bourcier Romain Guile Melanie Walker Malveeka Sharma Don Frei Pascal Jabbour Nabeel Herial Fawaz Al-Mufti Atilla ozcan ozdemir ozlem Aykac Dheeraj Gandhi Chandril Chugh Charles Matouk Pascale Lavoie Randall Edgell Andre Beer-Furlan Michael Chen Monika Killer-oberpfalzer Vitor Mendes Pereira Patrick Nicholson Vikram Huded Nobuyuki ohara Daisuke Watanabe Dong Hun Shin Pedro SC Magalhaes Raghid Kikano Santiago ortega-Gutierrez Mudassir Farooqui Amal Abou-Hamden Tatsuo Amano Ryoo Yamamoto Adrienne Weeks Elena A Cora Rotem Sivan-Hoffmann Roberto Crosa Markus Möhlenbruch Simon Nagel Hosam Al-Jehani Sunil A Sheth Victor S Lopez Rivera James E Siegler Achmad Fidaus Sani Ajit S Puri Anna Luisa Kuhn Gianmarco Bernava Paolo Machi Daniel G Abud octavio M Pontes-Neto Ajay K Wakhloo Barbara Voetsch Eytan Raz Shadi Yaghi Brijesh P Mehta Naoto Kimura Mamoru Murakami Jin Soo Lee Ji Man Hong Robert Fahed Gregory Walker Eiji Hagashi Steve M Cordina Hong Gee Roh Ken Wong Juan F Arenillas Mario Martinez-Galdamez jordi Blasco Alejandro Rodriguez Vasquez Luisa Fonseca M Luis Silva Teddy Y Wu Simon john Alex Brehm Marios Psychogios William J Mack Matthew Tenser Tatemi Todaka Miki Fujimura Roberta Novakovic Jun Deguchi Yuri Sugiura Hiroshi Tokimura Rakesh Khatri Michael Kelly Lissa Peeling Yuichi Murayama Hugh Stephen Winters johnny Wong Mohamed Teleb Jeremy Payne Hiroki Fukuda Kosuke Miyake Junsuke Shimbo Yusuke Sug Neurology RadiologyBoston Medical CenterBostonMassachusettsUSA Neurology Marcus Stroke&Neuroscience CenterGrady Memorial HospitalEmory University School of MedicineAtlantaGAUSA Radiology Radiation OncologyBoston University School of MedicineBostonMassachusettsUSA Neurology National Hospital Organization Osaka National HospitalOsakaJapan Neurosurgery National Hospital Organization Osaka National HospitalOsakaJapan Neurology Alexandria UniversityAlexandriaEgypt Radiology Boston Medical CenterBostonMassachusettsUSA Department of Neurology Xinqiao HospitalChongqingChina Neurosurgery University of Cape TownRondeboschWestern CapeSouth Africa Neurosurgery Interventional NeuroradiologyClinica La Sagrada FamiliaBuenos AiresArgentina Neuroradiologie Neurologie VasculaireHospices Civils de LyonLyonAuvergne-Rhône AlpesFrance Neurologie Vasculaire Hospices Civils de LyonLyonAuvergne-Rhône AlpesFrance Interventional Neuroradiology Fondation Ophtalmologique Adolphe de RothschildParisÎle-de FranceFrance Neurology Hospital Geral de FortalezaFortalezaBrazil Interventional Neuroradiology Hospital Geral de FortalezaFortalezaBrazil Neuroradiology Nottingham University Hospitals NHS TrustNottinghamUK Department of Neurosurgery Kobe City Medical Center General HospitalKobeHyogoJapan Interventional Neurovascular Unit University Hospital CareggiFirenzeToscanaItaly Neuroradiology University Hospital Centre ZagrebZagrebCroatia Interventional Neuroradiology Hopital BicetreLe Kremlin-BicetreFrance Stroke and Interventional Neuroradiology Lahore General HospitalLahorePakistan Neurological Institute Cleveland Clinic Abu DhabiAbu DhabiUAE Department of Radiology Beaumont HospitalDublinIreland Neurology Stroke UnitHospital-Estadual CentralVitoriaBrazil Neuroradiology Instituto de Neurocirugia Dr AsengoSantiagoChile Interventional Neuroradiology Institut National de NeurologieTunisTunisia Neurology Boston Medical CenterBostonMassachusettsUSA Neurosurgery Boston Medical Center

Background During the CoVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were *** study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ruptured aneurysm coiling interventions demonstrated similar *** We conducted a cross-sectional,retrospective,observational study across 6 continents,37 countries and 140 comprehensive stroke *** with the diagnosis of SAH,aneurysmal SAH,ruptured aneurysm coiling interventions and CoVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases,10th Revision,*** 3-month cumulative volume,monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before(1 year and immediately before)and during the pandemic,defined as 1 March-31 May *** prior 1-year control period(1 March-31 May 2019)was obtained to account for seasonal *** There was a significant decline in SAH hospitalisations,with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic,representing a relative decline of 22.5%(95%CI−24.3%to−20.7%,polisation of ruptured aneurysms declined with 1170-1035 procedures,respectively,representing an 11.5%(95%CI−13.5%to−9.8%,p=0.002)relative *** analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations,a 24.9%relative decline(95%CI−28.0%to−22.1%,poiling was noted in low coiling volume hospitals of 41.1%(95%CI 32.3%to 50.6%,p=0.008)despite a decrease in SAH admissions in this *** There was a relative decrease in the volume of SAH hospitalisations,aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the CoVID-19 *** findings in SAH are consistent with a decrease in other emergencies,such as stroke and myocardial infarction.

关键词： diagnosis representing subarachnoid

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