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Gene therapy for Parkinson’s Disease and Ethical Challenges: A Systematic Review

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Advances in Parkinson's Disease 2023年第2期12卷 9-28页

作者： Théodora m. Zohoncon Joseph Sawadogo Abdou Azaque Zoure Abdoul Karim Ouattara marie N. L. Ouedraogo Luc Zongo Paul Ouedraogo Florencia W. Djigma Christelle W. m. Nadembèga Raphael Kabore Djénéba Ouermi Dorcas Obiri-Yeboah jacques Simpore Pietro Annigoni biomolecular Research Centre (CERbA) Ouagadougou Burkina Faso Faculty of medicine University Saint Thomas d’Aquin (USTA) Ouagadougou Burkina Faso Saint Camille Hospital Ouagadougou (HOSCO) Ouagadougou Burkina Faso molecular biology and Genetics Laboratory (LAbIOGENE) Joseph KI-ZERBO University Ouagadougou Burkina Faso National Center for Scientific and Technological Research (CNRST/IRSS) Ouagadougou Burkina Faso Norbert Zongo University/manga University Centre Koudougou Burkina Faso Department of microbiology and Immunology School of Medical Sciences University of Cape Coast Cape Coast Ghana

background: Parkinson’s disease (PD) is a complex, multifactorial neurodegenerative disorder with a pathophysiology deriving from the synergy of abnormal aggregation of neuroinflammation, synuclein and dysfunction of lysosomes, mitochondria and synaptic transport difficulties influenced by genetic and idiopathic factors. Worldwide, PD has a prevalence of 2-3% in people over the age of 65. To date, there is no certified, effective treatment for PD. Aim: The aims of this research were: (i) to present, on the basis of recent advances in molecular genetics and epigenetics, the genomic aspects and challenges of gene therapy trials for PD;(ii) to outline the ethical principles applicable to therapeutic trials for PD. method: A systematic literature review was carried out to identify relevant articles reporting on genomic aspects and gene therapy in PD from 2001 to October 2023. The search was conducted in French and/or English in three databases: Pubmed, Google Scholar and Science Direct. PRISmA guidelines were used in this systematic review. Results: A total of thirty-three publications were selected. An inductive thematic analysis revealed that numerous genetic mutations (SNCA, Parkin, PINK1, DJ-1, LRRK2, ATP13A2, VPS35, Parkin/PRKN, PINK1, DJ1/PARK7) and epigenetic events such as the action of certain miRNAs (miR-7, miR-153, miR-133b, miR-124, miR-137) are responsible for the onset of PD, and that genetic therapy for this pathology raises ethical questions that need to be elucidated in the light of the bioethical principles of autonomy, beneficence, non-maleficence and justice. Conclusion: There is no zero risk in biotechnology. Then, it will be necessary to assess all the potential risks of Parkinson disease’s gene therapy to make the right decision. It is therefore essential to pursue research and, with the guidance of ethics, to advance treatment options and meet the challenges of brain manipulation and its impact on human identity. The golden rule of medicine remai

关键词： Neurodegenerative Diseases Parkinson Disease molecular mechanism Gene Therapy Gene Therapy Ethics

Interest of beta-2-microglobilin Plasma Assay in Iterative Haemodialysis in the Nephrology and Haemodialysis Department of University Teaching Hospital of Point G, bamako, mali

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Open Journal of Nephrology 2020年第4期10卷 282-289页

作者： Saharé Fongoro magara Samaké Seydou Sy Hamadoun Yattara Djénèba Diallo jacques Coulibaly moctar Coulibaly Aboubacar Sidiki Fofana Atabième Kodio Djénéba maiga Aboudou m. Dolo moustapha Tangara Nouhoum Coulibaly brahima Dégoga Ibrahima Koné Nephrology and Haemodialysis Department of the University Teaching Hospital of Point-G Bamako Mali Faculty of medicine of bamako Bamako Mali Nephrology Unit of the Fousseyni DAOU Hospital in Kayes Kayes Mali Nephrology Unit of Ségou Hospital Ségou Mali Nephrology Unit of the mali GAVARDO Hospital of Sébénicoro Bamako Mali Nephrology Unit of Sikasso Hospital Sikasso Mali Nephrology Unit of Somino DOLO Hospital in mopti Mopti Mali

beta-2-microglobulin (b2m) is a low molecular weight polypeptide (11,800 Da) that exists in a free form and a form.bound to cell membranes (light chains of HLA class I molecules). Their dosage is used in the exploration and monitoring of renal function in haemodialysis patients, hence the interest of this study, the objective of which is to study the different players involved in the increase of beta-2-microglobulin. materials and methods: This was a prospective and descriptive study from January 1st, 2017 to August 31, 2017 (08 months). All patients with chronic hemodialysis for 3 years or more were included. We analyzed sociodemographic, clinical and paraclinical data. Results: We collected 50 patients. The mean age was 50 ± 4.6 years with extremes of 30 and 82 years. The female sex predominated (52%). Chronic end-stage renal failure was hypertensive (86%), diabetic (4%). All patients benefited from intermittent hemodialysis for 8 hours per week using a low permeability membrane (cuprophane). The average duration of hemodialysis was 68 ± 6.4 months with extremes of 36 and 204 months. Twenty percent (20%) and four percent (4%) of chronic dialysis patients had joint pain and sensory deficit. Phalen’s sign was positive in 2% (1 case), Tinel’s sign in 2% (1 case) and carpal tunnel syndrome in 2% (1 case). The mean serum.beta-2-microglobulin level was 58.34 ng/l with extremes of 16.99 and 112.24 ng/l. There was a correlation between hypertensive nephropathies and beta-2-microglobulin levels above 50 ng/l (P mortality rate was 6%. Conclusion: Our study has objectified factors such as inadequate dialysis (8 hours/week), use of low permeability membrane in the increase of beta-2-microglobulin. The increase in serum.beta-2-microglobulin levels in our patients is evidence of poor purification of medium molecules. Its reduction can be established by improving the quality of dialysis, in particular by

关键词： Chronic Hemodialysis beta-2-microglobulin Carpal Tunnel Syndrome

Performance and calibration of quark/gluon-jet taggers using 140 fb^(-1) of pp collisions at √s=13 TeV with the ATLAS detector

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Chinese Physics C 2024年第2期48卷 1-25页

作者： G. Aad b. Abbott K. Abeling N.J. Abicht S.H. Abidi A. Aboulhorma H. Abramowicz H. Abreu Y. Abulaiti b.S. Acharya C. Adam.bourdarios L. Adamczyk S.V. Addepalli m.J. Addison J. Adelman A. Adiguzel T. Adye A.A. Affolder Y. Afik m.N. Agaras J. Agarwala A. Aggarwal C. Agheorghiesei A. Ahmad F. Ahmadov W.S. Ahmed S. Ahuja X. Ai G. Aielli A. Aikot m. Ait Tamlihat b. Aitbenchikh I. Aizenberg m. Akbiyik T.P.A. Åkesson A.V. Akimov D. Akiyama N.N. Akolkar K. Al Khoury G.L. Alberghi J. Albert P. Albicocco G.L. Albouy S. Alderweireldt m. Aleksa I.N. Aleksandrov C. Alexa T. Alexopoulos F. Alfonsi m. Algren m. Alhroob b. Ali H.m.J. Ali S. Ali S.W. Alibocus m. Aliev G. Alimonti W. Alkakhi C. Allaire b.m.m. Allbrooke J.F. Allen C.A. Allendes Flores P.P. Allport A. Aloisio F. Alonso C. Alpigiani m. Alvarez Estevez A. Alvarez Fernandez m. Alves Cardoso m.G. Alviggi m. Aly Y. Amaral Coutinho A. Ambler C. Amelung m. Amerl C.G. Ames D. Amidei S.P. Amor Dos Santos K.R. Amos V. Ananiev C. Anastopoulos T. Andeen J.K. Anders S.Y. Andrean A. Andreazza S. Angelidakis A. Angerami A.V. Anisenkov A. Annovi C. Antel m.T. Anthony E. Antipov m. Antonelli F. Anulli m. Aoki T. Aoki J.A. Aparisi Pozo m.A. Aparo L. Aperio bella C. Appelt A. Apyan N. Aranzabal S.J. Arbiol Val C. Arcangeletti A.T.H. Arce E. Arena J-F. Arguin S. Argyropoulos J.-H. Arling O. Arnaez H. Arnold G. Artoni H. Asada K. Asai S. Asai N.A. Asbah J. Assahsah K. Assamagan R. Astalos S. Atashi R.J. Atkin m. Atkinson H. Atmani P.A. Atmasiddha K. Augsten S. Auricchio A.D. Auriol V.A. Austrup G. Avolio K. Axiotis G. Azuelos D. babal H. bachacou K. bachas A. bachiu F. backman A. badea P. bagnaia m. bahmani A.J. bailey V.R. bailey J.T. baines L. baines O.K. baker E. bakos D. bakshi Gupta V. balakrishnan R. balasubramanian E.m. baldin P. balek E. ballabene F. balli L.m. baltes W.K. balunas J. balz E. banas m. bandieramonte A. bandyopadhyay S. bansal L. barak m. barakat E.L. barberio D. barberis m. barbero m.Z. barel K.N. barends T. barillari m-S. barisits T. barklow P. baron D.A. baron mo The ATLAS Collaboration

The identification of jets originating from quarks and gluons,often referred to as quark/gluon tagging,plays an important role in various analyses performed at the Large Hadron Collider,as Standard model measurements and searches for new particles decaying to quarks often rely on suppressing a large gluon-induced *** paper describes the measurement of the efficiencies of quark/gluon taggers developed within the ATLAS Collaboration,using √s=13 TeV proton–proton collision data with an integrated luminosity of 140 fb^(-1) collected by the ATLAS *** taggers with high performances in rejecting jets from gluon over jets from quarks are studied:one tagger is based on requirements on the number of inner-detector tracks associated with the jet,and the other combines several jet substructure observables using a boosted decision tree.A method is established to determine the quark/gluon fraction in data,by using quark/gluon-enriched subsamples defined by the jet *** in tagging efficiency between data and simulation are provided for jets with transverse momentum.between 500 GeV and 2 TeV and for multiple tagger working points.

关键词： ATLAS JET QUARK GLUON TAGGING

Hepatitis b and C Immunological and molecular Parameter Analysis in HIV-Positive Patients Undergoing Antiretroviral Therapy at Saint Camille Hospital in Ouagadougou (HOSCO), burkina Faso

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Advances in Infectious Diseases 2022年第1期12卷 20-41页

作者： Denise P. Ilboudo W. W. Eudoxie Kévine Savadogo Théodora m. Zohoncon Estelle Savadogo Yéri Esther Hien Lassina Traore Djéneba Ouermi Wendkuuni Florencia Djigma Christelle m. Nadembega marius belemgnegre Paul Ouedraogo mahamoudou Sanou Damintoti Simplice Karou Yves Traore jacques Simpore Laboratory of molecular biology and molecular Genetics (LAbIOGENE) UFR/SVT University Joseph KI-ZERBO Ouagadougou Burkina Faso University of Fada N’Gourma Fada N’Gourma Burkina Faso Laboratory of biochemistry and Applied Immunology University Joseph KI-ZERBO Ouagadougou Burkina Faso biomolecular Research Center Pietro Annigoni (CERbA) Ouagadougou Burkina Faso Université Saint Thomas d’Aquin Faculté de Médecine Ouagadougou Burkina Faso Hopital Saint Camille Ouagadougou (HOSCO) Ouagadougou Burkina Unité de Formation et de Recherche en Science De la Santé (UFR/SDS) Université Joseph KI-ZERBO (UJKZ) Ouagadougou Burkina Faso Ecole Supérieure des Techniques biologiques et Alimentaires (ESTbA-UL) Université de Lomé Lomé Togo

Knowledge of the clinical and biological profile of patients infected with HIV and hepatitis b and/or C is essential in order to identify and implement effective management strategies. methods: This was a retrospective descriptive study from January 01, 2016 to June 01, 2021. Adult patients aged at least 18 years infected with HIV type 1 and/or 2, na?ve to ARV treatment. Univariate analyses were assessed using Pearson’s Chi2 test. The Student Newman test was used for comparison between groups using R software version 4.0.2. Objective: To draw up the epidemiological, clinical, paraclinical and evolutionary profiles of HIV-treated-patients in relation to HIV/HbV and HIV/HCV co-infections in order to allow the identification and the implementation of effective management strategies. Results: Of the 379 patients included 280 (73.88%) were women. At treatment initiation, the mean age was 40.14 ± 11.84 years. The majority of patients consulted at WHO stage III (51.45%). Clinical suspicion was the most frequent screening circumstance (51.71%). The pathologies frequently reported at the first consultation were diarrhea (28%) and shingles (16%). body mass index was normal in 50.5% of patients. HIV1 infection was the majority (91.03%). A total of 270 had a CD4 count at treatment initiation. The mean CD4 cell count was 304.17 ± 242.06 cells/μL, and 116 (42.59%) of them had a CD4 ≤ 200 cells/μL. Viral load at treatment initiation was documented in 62 patients (16.35%) and 70.97% of them had a detectable viral load (greater than 1000 copies/mL). The clinical and biological evolution was relatively good in patients after therapeutic initiation. HIV-HbV co-infection was 24.11% and HIV-HCV co-infection was 2.26%. The mortality rate was 3.69%. Conclusion: These results reflect a significant delay in HIV infection diagnosis. Furthermore, hepatitis b and/or C is co-infections that increasingly affect people living with HIV. It also appears that COVID 19 disease has had a strong impact

关键词： HIV Clinical-biological Profile Hepatitis b and C Co-Infection burkina Faso

Specificity of serological screening tests and reference laboratory tests to diagnose gambiense human African trypanosomiasis: a prospective clinical performance study

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Infectious Diseases of Poverty 2024年第4期13卷 48-63页

作者： martial Kassi N'Djetchil Oumou Camara mathurin Koffi mamadou Camara Dramane Kaba jacques Kabore Alkali Tall brice Rotureau Lucy Glover melika barkissa Traorel minayegninrin Kone bamoro Coulibaly Guy Pacome Adingra Aissata Soumah mohamed Gassama Abdoulaye Dansy Camara Charlie Franck Alfred Compaore Aissata Camara Salimatou boiro Elena Perez Anton Paul bessell Nick Van Reet bruno bucheton Vincent Jamonneau Jean-mathieu bart Philippe Solano Sylvain bieler Veerle Lejon Laboratory of biodiversity and Ecosystem management Jean Lorougnon Guede UniversityDaloaCote d'ivoire National Program for Neglected Tropical Disease Control Patient ManagementMinistry of HealthConakryGuinea Trypanosomosis Research Unit Pierre Richet InstituteBouakeCote d'ivoire International Research and Development Centre on Livestock in Subhumid Zones Bobo-DioulassoBurkina Faso National Program for malaria Control ConakryGuinea Parasitology Unit Institut Pasteur de GuineeConakryGuinea Trypanosome molecular biology Unit Department of Parasites and Insect VectorsPasteur InstituteParis Cite UniversityParisFrance Intertryp IRD-CIRAD-University of MontpellierMontpellierFrance Independent Consultant EdinburghUk Department of biomedical Sciences Institute of Tropical MedicineAntwerpBelgium Foundation for Innovative New Diagnostics GenevaSwitzerland

background Serological screening tests play a crucial role to diagnose gambiense human African trypanosomiasis(gHAT).Presently,they preselect individuals for microscopic confrmation,but in future"screen and treat"strategies they willidentify individuals for *** in reported specificities,the development of new rapid diagnos-tic tests(RDT)and the hypothesis that malaria infection may decrease RDT specificity led us to evaluate the specificity of 5 gHAT screening *** During active screening,venous blood samples from 1095 individuals from Cote d'ivoire and Guinea were tested consecutively with commercial(CATT,HAT Sero-K-SeT,Abbott bioline HAT 2.0)and prototype(DCN HAT RDT,HAT Sero-K-SeT 2.0)gHAT screening tests and with a malaria *** with≥1 positive gHAT screening test underwent microscopy and further immunological(trypanolysis with *** LiTat 1.3,1.5 and 1.6;indirect ELISA/***;*** inhibition ELISA with *** LiTat 1.3 and 1.5 VSG)and molecular reference laboratory tests(PCR TbRN3,18S and TgsGP;SHERLOCK 18S Tids,7SL Zoon,and TgsGP;Trypanozoon S2-RT-qPCR 18S2,177T,GPl-PLC and TgsGP in multiplex;RT-qPCR DT8,DT9 and TgsGP in multiplex).microscopic trypanosome detection confrmed gHAT,while other individuals were considered gHAT *** in fractions between groups were assessed by Chi square and differences in specificity between 2 tests on the same individuals by *** One gHAT case was *** test specificities(n=1094)were:CATT 98.9%(95%CI:98.1-99.4%);HAT Sero-K-SeT 86.7%(95%CI:84.5-88.5%);bioline HAT 2.082.1%(95%CI:79.7-84.2%);DCN HAT RDT 78.2%(95%CI:75.7-80.6%);and HAT Sero-K-SeT 2.078.4%(95%CI:75.9-80.8%).In malaria positives,gHAT screening tests appeared less specific,but the difference Was significant only in Guinea for Abbott bioline HAT 2.0(P=0.03)and HAT Sero-K-Set 2.0(P=0.0006).The specificities of immunological and molecular laboratory tests in gHAT seroposit

关键词： Human African trypanosomiasis Trypanosoma brucei gambiense Diagnosis Specificity Rapid diagnostic test Immunoloaical test molecular test

Spectrum of meningitis in Adult at the Douala General Hospital

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World Journal of Neuroscience 2014年第2期4卷 144-151页

作者： Yacouba N. mapoure Henry N. Luma Dieudonné Gnonlonfoun Paul m. Ossou-Guiet Xaverie biloa jacques N. Doumbe Hugo bertrand N. mbatchou benjamin Clet N. Tchaleu Julius Y. Fonsah Albert S. mouelle Alfred K. Njamnshi Department of Clinical Sciences Douala General Hospital Douala Cameroon Department of Clinical Sciences The University of Douala Douala Cameroon Department of Clinical Sciences Université des Montagnes Douala Cameroon Department of Neurology Brazzaville University Teaching Hospital Brazzaville Congo Department of Neurology National University Hospital Centre Cotonou Bénin Department of Neurology The University of Yaoundé I Yaoundé Cameroon Department of Neurology Yaoundé Central Hospital Yaoundé Cameroon

Objectives: Describe the clinical, aetiological and prognostic features of infectious meningitis in adults at the Douala General Hospital (DGH). Patients and methods: We carried out a 5-year retrospective cross-sectional study at the DGH, on data from the registers of the bacteriology and biochemistry laboratories. Cases of meningitis were identified from the results of the cerebrospinal fluid (CSF) analysis, and the patient clinical file was obtained. Cases files of patients aged 15 years and above were included. For each patient, sociodemographic, clinical features and hospital mortality data were extracted. Results: During study period, 1877 CSF analyses were recorded and 135 were enrolled for data analysis. Up to 74 patients (55%) were male and the mean age was 40.04 ± 12.5 years. The time lapse between the onset of symptoms and consultation was 12.24 ± 11.16 days. The main clinical signs were meningeal syndrome (96.3%), neck stiffness (71.1%), reduced alertness (64.4%) and confusional states (55.6%). The main aetiology was bacterial (45.19%) withStreptococcus pneumoniae?(45.90%) and?Neisseria meningitis?(29.51%) leading. The other aetiologies were viral (21.48%), fungal with?Cryptococcus neoformans?(20%) and meningeal tuberculosis (13.33%). Fifty eight patients (42.9%) had a positive HIV serology. The mean duration of hospitalization was 9.05 ± 8.1 days, and the total in-hospital mortality was 25.18%. 117 patients (86.8%) had received antibiotherapy before diagnosis. Conclusion: The clinical features of meningitis in the DGH are as in classical description. However, the mortality is high and the major aetiologies appear to be associated with HIV infection at least in part. Prospective multi-centric studies are needed to provide more evidence for the development of staged management guidelines in our resource-limited settings.

关键词： meningitis Signs Aetiologies mortality Adults Douala Cameroon

Evolution of HbV Viral Load during Clinical and biological Follow-Up of Chronic Hepatitis b Patients at the Saint Camille Hospital in Ouagadougou

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Advances in Infectious Diseases 2023年第4期13卷 550-563页

作者： Théodora mahoukèdè Zohoncon T. Rose Clémence Ido Da Nicaise Zagre Pauline belemkoabga Denise P. Ilboudo Abdoul Karim Ouattara Paul Ouedraogo jacques Simpore Department of molecular biology H&#244pital Saint Camille de Ouagadougou (HOSCO) Ouagadougou Burkina Faso Faculté de médecine Université Saint Thomas d’Aquin (USTA) Ouagadougou Burkina Faso Laboratoire de biologie moléculaire et de Génétique (LAbIOGENE) Université Joseph KI-ZERBO Ouagadougou Burkina Faso Centre de Recherche biomoléculaire Pietro Annigoni (CERbA) Ouagadougou Burkina Faso

Hepatitis b virus (HbV) infection is a major public health problem worldwide. The aim of this study was to document the dynamics of HbV viral load during the follow-up of chronic hepatitis b patients at the Saint Camille Hospital in Ouagadougou (HOSCO) from 2017 to 2021. This descriptive retrospective study was carried out in the Hepato-Gastro-Enterology Department of HOSCO and focused on patients who were undergoing treatment for chronic viral hepatitis b. A total of 260 cases of chronic hepatitis b were included in the study. The most affected age group was 21 to 30 years, accounting for 48.08% of the cases. Lifestyle factors included alcohol consumption (3.08%) and tobacco use (2.69%). major risk factors for transmission included lack of vaccination (98.46%), family history of HbV infection (68.00%) and engagement in high-risk activities (28.00%). Patients requiring treatment were prescribed Tenofovir 300 mg tablets. FibroScan® showed the presence of stage F3-F4 fibrosis (2.14%) and S3 steatosis (13.33%). After one year of follow-up, 6.92% of patients achieved an undetectable viral load with normalized transaminase levels. The majority of other patients had a detectable viral load but below 20,000 IU/mL. The prevalence of viral hepatitis b remains significant worldwide. Although effective and well-monitored treatment can lead to undetectable viremia, prevention remains the most effective strategy for successful management of this disease.

关键词： Chronic Viral Hepatitis b Viral DNA Follow-Up Evolution of Viral Load

一种兼具高强度、高应变硬化率和高塑性的新型钛合金

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世界有色金属 2015年第3期40卷 31-34页

作者：逯冉 F.Sun J.Y.Zhang m.marteleur C.brozek E.F.Rauch m.Veron P.Vermaut P.J.jacques F.Prim 北京中色鑫桥商贸中心 Institut de Recherche de Chimie Paris CNRS UMR 8247–Chimie Paris Tech 11 rue Pierre et Marie Curie75005 Paris France Universite'Catholique de Louvain Institute of MechanicsMaterials and Civil Engineering IMAP Place Sainte Barbe 2B-1348 Louvain-la-Neuve Belgium Univ.Grenoble Alpes SIMAP F-38000 Grenoble France CNRS SIMAP F-38000 Grenoble France Universite' Catholique de Louvain Institute of MechanicsMaterials and Civil Engineering IMAP Place Sainte Barbe 2B-1348 Louvain-la-Neuve Belgium

本研究设计了一种三元亚稳β钛合金Ti-9mo-6W(质量百分数)。由于该合金变形时会联合出现相变诱发塑性效应和孪晶诱发塑性效应,使该合金的加工硬化速率可以接近2 100mPa,均匀变形能力高于35%。为了深入了解Ti-9mo-6W合金的变形过程,对其... 详细信息

本研究设计了一种三元亚稳β钛合金Ti-9mo-6W(质量百分数)。由于该合金变形时会联合出现相变诱发塑性效应和孪晶诱发塑性效应,使该合金的加工硬化速率可以接近2 100mPa,均匀变形能力高于35%。为了深入了解Ti-9mo-6W合金的变形过程,对其变形过程中的显微组织进行了详细分析。结果表明,Ti-9mo-6W合金变形过程中存在{332}机械孪晶、应力诱发ω相、应力诱发α"马氏体等不同的变形机制,综合作用使合金内部最终形成了具有高度协合性的复杂网络变形组织。

关键词：钛合金孪晶马氏体相变转变组织

CmV蚜传相关蛋白CP基因的克隆与变异分析

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CMV蚜传相关蛋白CP基因的克隆与变异分析