Institut National De La Sante Research Articles

Research trends of glioma-related epilepsy: A bibliometric analysis from 2004 to 2023.

Glioma-related epilepsy (GRE) is a hotspot in recent years and there remains many urgent unsolved issues. This study aimed to conduct bibliometric analysis on GRE research over the past 2 decades. We collected scientific outputs relating to GRE on Web of Science Core Collection (WoSCC) from 2004 to 2023 and conducted visual analysis using VOSviewer and Microsoft Excel. A total of 2697 publications were retrieved with an increasing trend over the past 20years. The USA ranked first in publication number, total citation and H-index. Institut National de la Sante et de la Recherche Medicale (Inserm) was the institution with the most publications. In the field of GRE, core journals were Journal of Neurosurgery, Epilepsia and Neurology. Duffau, Hugues was the author with the most papers and total citations, and the highest H-index. Co-occurrence analysis revealed that the latest research focus of GRE were awake craniotomy, immunotherapy, cognitive impairment, and basic research on pathogenesis, with particular emphasis on the IDH1 mutation. This study intended to gain a deeper understanding of the current global GRE research and identify hotspots, as well as to provide theoretical reference for further studies.

Assessment of the Daily Living Activities of Older People (2004-2023): A Bibliometric and Visual Analysis.

With a rapidly aging global population, comprehending the risks associated with older people's activities of daily living is increasingly important; yet, interdisciplinary analyses remain rare. By providing a bibliometric overview of the capability risks associated with older people's activities of daily living, in order to identify prevailing trends and future directions in the field, the study aims to fill this gap. Using CiteSpace software to analyze data from 928 articles published between 2004 and 2023, the study results demonstrate the growing interest in the capability risks of older people's activities of daily living, with the United States leading in the number of publications, and geriatrics emerging as the dominant discipline. Notably, Institut National de la Sante et de la Recherche Medicale (Inserm) in France emerges as a pivotal contributor in the field. Key research topics encompass risk factors associated with a decline in daily activities and disease-related studies, with emerging trends in cognitive function and instrumental activity research. Future research should prioritize the development of predictive mechanisms for daily living trends, exploration of caregiving solutions, and promotion of interdisciplinary collaboration. This study highlights promising avenues for further research, emphasizing the importance of predictive modeling, innovative caregiving strategies, and interdisciplinary cooperation in addressing capability risks in the activities of daily living of older people.

Bibliometric and visual analysis of membranous nephropathy literature from 2010 to 2023.

Membranous glomerulonephritis, also known as membranous nephropathy (MN), is a common cause of nephrotic syndrome in adults. Despite extensive research on MN, bibliometric studies on the subject are scarce. Therefore, this study aimed to provide a visual analysis of global trends in membranous nephropathy research over the past 13years. This study conducted a bibliometric and visual analysis of global trends in MN research from 2010 to 2023. Articles related to MN were retrieved from the Web of Science Core Collection (WoSCC) database. Tools such as CiteSpace and VOSviewer were utilized to analyze publications, countries, institutions, authors, publishing journals, co-cited references, and keywords to identify the current state and future trends in MN research. The analysis encompassed 1,624 publications, showing an annual increase from 2010 to 2023. The People's Republic of China emerged as the most active country in this field, while France's Sorbonne Universite and Institut National de la Sante et de la Recherche Medicale (Inserm) led in publication volume among academic institutions. Debiec Hanna stood out as the most prolific author. BMC Nephrology had the highest number of publications, making it the most favored journal in the field. The article with the greatest co-citation intensity was "Primary Membranous Nephropathy," a review published in 2017. This study shows that there has been increasing interest in membranous nephropathy over the past 13 years. The most frequently encountered keywords were "membranous nephropathy" "nephrotic syndrome," and "glomerulonephritis." Analysis of emerging terms indicated that "a2 receptor antibody," "domain containing 7a," and "t cell" may remain prominent subjects of research in the forthcoming years. The findings highlight key research trends and areas of interest that can inform researchers, clinicians, and policymakers about the current state of MN research and help guide future research directions and clinical practice.

Crohn's disease from past to present: Research trends and global outcomes with scientometric analysis during 1980 to 2022.

Currently, there is no comprehensive bibliometric study in the literature on Crohn's disease (CD). The aim of this study was to analyze articles published on CD using bibliometric and statistical methods. The aim was to identify current research trends, show global productivity, and determine important players such as countries, journals, institutions, and authors. A total of 16,216 articles published on CD between 1980 and 2022 were analyzed using various statistical and bibliometric methods. Bibliometric network visualization maps were used to perform trend topic analysis, citation analysis, and international collaboration analysis. Spearman's correlation coefficient was used for correlation analysis. The top 3 contributing countries to the literature were the United States of America (USA) (n = 4344, 26.7%), the United Kingdom (UK) (n = 2036, 12.5%) and Germany (n = 1334, 8.2%). The most active institutions were Udice French Research Universities (n = 696), Assistance Publique Hopitaux Paris (n = 570), and Institut National de la Sante et de la Recherche Medicale Inserm (n = 479). The most productive journals were Inflammatory Bowel Diseases (n = 1100), Journal of Crohn's & Colitis (n = 579), and Gut (n = 510). The most prolific author was Colombel JF. (n = 290). The most frequently researched topics from past to present included infliximab, ulcerative colitis, surgery, pediatrics, adalimumab, magnetic resonance imaging, inflammation, perianal CD/perianal fistula, azathioprine, magnetic resonance enterography, small bowel, stricture/strictureplasty, recurrence, therapy/treatment, ustekinumab, mucosal healing, biomarkers, fistula, quality of life, ultrasonography, epidemiology, capsule endoscopy, laparoscopic surgery/laparoscopy, endoscopy, disease activity, postoperative recurrence, and the Nucleotide Binding Oligomerization Domain Containing 2 gene. We have seen an exponential increase in worldwide publications on CD. In recent years, the major research topics related to CD have been ustekinumab, vedolizumab, fecal calprotectin, therapeutic drug monitoring, biologics, biomarkers, exclusive enteral nutrition, microbiome/microbiota, magnetic resonance enterography, anti-TNF, postoperative complications, and mucosal healing. We determined that countries with large economies, particularly the United States, United Kingdom, Germany, France, Canada, Italy, Japan and China, have taken the lead in research contributions to the development of CD literature.

Knowledge fields and emerging trends about extracellular matrix in carotid artery disease from 1990 to 2021: analysis of the scientific literature

BackgroundStroke is a heavy burden in modern society, and carotid artery disease is a major cause. The role of the extracellular matrix (ECM) in the development and progression of carotid artery disease has become a popular research focus. However, there is no published bibliometric analysis to derive the main publication features and trends in this scientific area. We aim to conduct a bibliometric analysis to reveal current status of ECM in carotid artery disease and to predict future hot spots.MethodsWe searched and downloaded articles from the Web of Science Core Collection with “Carotid” and “Extracellular Matrix” as subject words from 1990 to 2021. The complete bibliographic data were analyzed by Bibliometrics, BICOMB, gCLUTO and CiteSpace softwares.ResultsSince 1990, the United States has been the leader in the number of publications in the field of ECM in carotid artery disease, followed by China, Japan and Germany. Among institutions, Institut National De La Sante Et De La Recherche Medicale Inserm, University of Washington Seattle and Harvard University are in the top 3. “Arteriosclerosis Thrombosis and Vascular Biology” is the most popular journal and “Circulation” is the most cited journal. “Clowes AW”, “Hedin Ulf” and “Nilsson Jan” are the top three authors of published articles. Finally, we investigated the frontiers through the strongest citation bursts, conducted keyword biclustering analysis, and discovered five clusters of research hotspots. Our research provided a comprehensive analysis of the fundamental data, knowledge organization, and dynamic evolution of research about ECM in carotid artery disease.ConclusionsThe field of ECM in carotid artery disease has received increasing attention. We summarized the history of the field and predicted five future hotspots through bibliometric analysis. This study provided a reference for researchers in this fields, and the methodology can be extended to other fields.

Estimates of global research productivity in primary ovarian insufficiency from 2000 to 2021: Bibliometric analysis.

Primary ovarian insufficiency (POI) is a heterogeneous disease with diverse clinical phenotypes and etiologies, which is defined as ovarian dysfunction under the age of 40 years. The global prevalence of POI is approximately about 1.1%, and it severely affects female fertility. Nevertheless, bibliometric analysis in this field is extremely limited. We aimed to visualize the research hotspots and trends of POI using bibliometric analysis and tried to predict the future development of this field. The original articles regarding POI were culled from the Web of Science Core Collection. Countries, institutions, journals, authors, and keywords in this field were visually analyzed by employing CiteSpace software and Microsoft Excel 2021 software. A total of 2,999 publications were included for further bibliometric analysis after screening the titles and abstracts stringently. The number of literature regarding POI significantly increased yearly. These publications come from 78 countries. The USA was dominant in the field of POI in terms of the number of publications (865), average citations per item (57.36), and h-index (112). The Institut National De La Sante Et De La Recherche Medicale Inserm is the most high-yield institution in this field with 351 publications. Fertility and Sterility ranked first with the highest number of publications (152), followed by Human Reproduction (138). According to the keyword cluster analysis from 2000 to 2021, the eight keyword clusters encountered frequently were apoptosis, osteoporosis, fertility preservation, mutation, fragile x syndrome, adrenal insufficiency, DNA repair, ovarian reserve. Keyword citation burst analysis revealed that whole-exome sequencing, ovarian tissue cryopreservation, and DNA repair had a citation burst until 2021. Great progress has been made in POI research over the past 20 years, which is widely researched but unevenly developed in the world. In terms of influence, the United States may be in the lead. The research hotspots in POI are mainly pathogenesis and treatment, including genetic mutation, hormone therapy, fertility preservation, and stem cell transplantation.

Pharmacovigilance Bibliometrics: Visualizing Thematic Development in the Category of Pharmacology and Pharmacy in Web of Science.

Introduction: Pharmacovigilance studies include monitoring and preventing the occurrence of new, rare, or serious adverse drug reactions, making it possible to discover new safety issues without delay. Bibliometrics could assist scholars to analyze the development of pharmacovigilance. Methods: The MeSH terms of both pharmacovigilance and “adverse drug reaction reporting system” were retrieved in the Science Citation Index Expanded. The articles from 1974 to July 2021 in the pharmacology and pharmacy category were recruited. The citation reports including the publication numbers, h-index, and sum and average cited times in terms of annuals, countries, organizations, authors and journals were tabulated. The coauthorship relations in the analysis units of countries, organizations, and authors; the top 10 burst references; the document citation network; and the author’s keywords co-occurrence overlay map were visualized by bibliometric software including the website (https://bibliometric.com/), VOSviewer, CiteSpace, and CitNetExplorer. Results: From 1974 to the present, the most high-yield publication year, country, institute, author, and journal were 2020 (n = 222), France (n = 522), Netherlands Pharmacovigilance Centre Lareb (n = 82), Jean–Louis Montastruc (n = 125), Drug Safety (n = 384), respectively, in all 2,128 articles. Similarly, the United States, Institut National de la Sante et de la Recherche Medicale, and Jean–Louis Montastruc had the most coauthorship strength at the macrolevel (global), mesolevel (local), and microlevel (individual). The topics of burst references covered are the development of methodology, issues of patients reporting and under-reporting, evaluation of methods and databases, assessment of causality, and perspectives in pharmacovigilance. Eight clusters were grouped in the document citation network. “Pharmacovigilance,” “adverse drug reactions,” “pharmacoepidemiology,” “drug safety,” and “signal detection” were the research priorities, while “drug-related side effects and adverse reactions,” “VigiBase,” “disproportionality analysis,” “social media,” “FAERS,” “chemotherapy,” “patient safety,” “reporting odds ratio,” and “preventability” might be the future research hotspots. Conclusion: Positive synergies can be observed in this study by employing the multiple software tools which established the relationship between the units of analysis. The bibliometric analysis can organize the thematic development and guide the hotspots of pharmacovigilance in pharmacology and pharmacy.

Remdesivir for the Treatment of Hospitalised Patients with COVID-19 (DisCoVeRy): A Randomised, Controlled, Open-Label Trial

Remdesivir for the Treatment of Hospitalised Patients with COVID-19 (DisCoVeRy): A Randomised, Controlled, Open-Label Trial

Social Inequalities and Dynamics of the COVID-19 Epidemic: Evidence from France

Background: Our main objective was to study the early social dynamics of the COVID-19 epidemic in France, taking into account gender, class, and ethnicity inequalities in living conditions.Methods: A random population-based survey was conducted in France in May 2020, during and post COVID-19 lockdown, in which 77,588 participants aged 18-64 were included in this study. We used multinomial regressions to identify changes in social position and exposure factors associated with symptoms of anosmia/ageusia during the first epidemic peak in late March and thereafter.Findings: In all, 2,045 (1.53% (95%CI 1.46%-1.61%)) participants reported anosmia/ageusia (1.13% during the epidemic peak and 0.40% after), with strong variations according to regions. Women and ethno-racial minorities remained at higher risk of anosmia/ageusia during and after the peak. Whereas senior executive professionals were more affected than lower social classes at the peak of the epidemic, this effect disappeared afterwards. Adjusting on key exposure factors substantially attenuated these associations, except for gender differences. While high density of the place of residence was associated with anosmia/ageusia during the peak, but no longer after, the opposite trend was observed for living in overcrowded housing. Having worked outside the home during lockdown was the most strongly associated exposure factor, and even more so after the peak.Interpretation: The shift in the social profile of the epidemic was related to a shift in exposure factors under the implementation of stringent collective prevention measures. Our results notably stress the importance of working outside the home, all the more so in essential occupations.Funding Statement: Inserm (Institut National de la Santé et de la Recherche Médicale).French Ministry for Research. Drees. Dr. Bajos has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. [856478])Declaration of Interests: None.Ethics Approval Statement: The survey was approved by the CNIL (French independent administrative authority responsible for data protection) on April 25th 2020 (ref: MLD/MFI/AR205138) and by the “Comité de protection des personnes” (French equivalent of the Research Ethics Committee) on April 24th. The survey also obtained an agreement from the “Comité du Label de la statistique publique”, proving its adequacy to statistical quality standards.

Seroprevalence of SARS-CoV-2 Among Adults in Three Regions of France Following the Lockdown and Associated Risk Factors: A Multicohort Study

Background: To estimate the seroprevalence of SARS-CoV-2 infection in May-June 2020 after the lockdown in adults living in three regions in France and to identify the associated risk factors.Methods: Participants in a survey on COVID-19 from an existing consortia of three general adult population cohorts living in the Ile-de-France (IDF) or Grand Est (GE) - two regions with high rate of COVID-19, or in the Nouvelle-Aquitaine (NA) – with a low rate, were asked to take a dried-blood spot (DBS) for anti-SARS-CoV-2 antibodies.The primary outcome was a positive anti-SARS-CoV-2 ELISA IgG result against the spike protein of the virus (ELISA-S). The secondary outcomes were a positive ELISA IgG against the nucleocapsid protein (ELISA-NP), anti-SARS-CoV-2 neutralizing antibodies titers ≥40 (SN), and predicted positivity obtained from a multiple imputation model (MI). Prevalence estimates were adjusted using sampling weights and post-stratification methods.Findings: Between May 4, 2020 and June 23, 2020, 16,000 participants were asked to provide DBS, and 14,628 were included in the analysis, 983 with a positive ELISA-S, 511 with a positive ELISA-NP, 424 with SN≥40 and 941±31 with a positive MI. Adjusted estimates of seroprevalence (positive ELISA-S) were 10.0% (95%CI 9.1%;10.9%) in IDF, 9.0% (95%CI 7.7%; 10.2%) in GE and 3.1% (95%CI 2.4%; 3.7%), in NA. The adjusted prevalence of positive ELISA-NP, SN and MI were 5.7%, 5.0% and 10.0% in IDF, 6.0%, 4.3% and 8.6% in GE, and 0.6%, 1.3% and 2.5% in NA, respectively. A higher seroprevalence was observed in younger participants and when at least one child or adolescent lived in the same household. A lower seroprevalence was observed in smokers compared to non-smokers.Interpretation: At the end of the lockdown the prevalence of anti-SARS-CoV-2 IgG or neutralizing antibodies remained low in the French adult population, even in regions with high reported rates of COVID-19.Funding Statement: ANR (Agence Nationale de la Recherche, #ANR-20-COVI-000, #ANR-10-COHO-06), Fondation pour la Recherche Médicale (#20RR052-00), Inserm (Institut National de la Santé et de la Recherche Médicale, #C20-26). Additional cohort funding is listed in the manuscript.Declaration of Interests: Prof Fabrice Carrat reports grants from INSERM-ANRS, during the conduct of the study; personal fees from Imaxio, outside the submitted work. Mathilde Touvier, Prof Gianluca Severi, Prof Laurence Meyer, Prof Florence Jusot, Nathanael Lapidus, Delphine Rahib, Nathalie Lydié, Hélène Blanché, Jean-François Deleuze, Marie-Aline Charles, Prof Pierre-Yves Ancel, Alexandra Rouquette, Claude Martin, Prof Xavier de Lamballerie, Prof Marie Zins, Nathalie Bajos declare no competing interest. The remaining authors have no competing interest to declare.Ethics Approval Statement: Ethical approval and written or electronic informed consent were obtained from each participant before enrolment in the original cohort. The SAPRIS survey was approved by the Inserm ethics committee (approval #20-672 dated March 30, 2020). The SAPRIS-SERO study was approved by the Sud-Mediterranée III ethics committee (approval #20.04.22.74247) and electronic informed consent was obtained from all participants for DBS testing.

Chantal M. Boulanger: Exploring the Endothelium.

The scientific evolution of Chantal M. Boulanger, PharmD, PhD, has taken her from a French village’s one-room schoolhouse to the Mayo Clinic to a leadership position at the Institut National de la Sante et de la Recherche Medicale (Inserm) in Paris. Chantal M. Boulanger While completing pharmacy studies at the Universite de Lorraine, Boulanger leapt at the chance to spend summers in research laboratories with the aim of pursuing a PhD. Her molecular pharmacology doctoral work, on the intracellular mechanisms associated with vascular smooth muscle relaxation, was conducted at the Universite de Strasbourg in the program headed by Jean-Claude Stoclet. Boulanger’s research career has focused on the role of endothelial cells as a key player in vascular disease development and as a target of cardiovascular risk factors. While she was a research associate at the University Hospital of Basel, Switzerland, Boulanger and T.F. Luscher demonstrated that production of the vasoconstrictor endothelin is downregulated by nitric oxide1 and stimulated by oxidized lipids2 in isolated endothelium, findings that were later confirmed in intact animals and provided new pharmacological targets to address endothelial dysfunction. In a change that required a major shift in laboratory techniques and models, since 2000 Boulanger’s research team at Inserm has investigated the extracellular microvesicles produced by endothelial cell activation. The team demonstrated that circulating microvesicles from patients with myocardial infarction triggered endothelial dysfunction, even in angiographically normal arteries.3 They identified microvesicles in human atherosclerotic plaque as potent prothrombogenic mediators that might represent a major determinant of plaque neovascularization and vulnerability.4 Later, they showed that circulating endothelial microvesicles were associated with cardiovascular and metabolic risk factors in participants in the Framingham offspring study who had no history of cardiovascular disease.5 Currently, Boulanger’s research addresses the regulation of micro-RNA packaging in extracellular vesicles and resulting …

From the Evaluation of Psychotherapies to Research in Psychotherapy and Psychoanalysis

Douze ans se sont écoulés depuis la publication de l’expertise Inserm : Psychothérapie, trois approches évaluées . Où en sommes-nous ? Au niveau international, les études concernant l’efficacité de l’approche psychanalytique se sont multipliées. Parallèlement, les comparaisons d’approches globales sont sorties des priorités de la recherche en psychothérapie, au profit d’études centrées sur les conditions et les causes intervenant dans les processus de changement. En France, un réseau Inserm de recherches fondées sur les pratiques psychothérapiques s’est constitué. Associant cliniciens et chercheurs, il développe depuis 2008 une méthodologie innovante sur l’action thérapeutique. À partir de l’étude approfondie de cas traités dans des conditions naturelles, ses perspectives sont cliniques, pratiques et théoriques. Une centaine de psychanalystes y participent dans les pôles autisme et borderline, et différentes publications rendent compte des observations réalisées.

Proceedings of First Histoplasmosis in the Americas and the Caribbean Meeting, Paramaribo, Suriname, December 4–6, 2015

Histoplasmosis is not defined as a neglected disease, but in Latin America and the Caribbean, it is suspected that nearly 10,000 HIV-positive patients die from histoplasmosis disseminated beyond the respiratory tract yearly, placing this AIDS-defining illness among the main causes of death of HIV patients on a similar level as HIV-associated tuberculosis (1,2). During December 4–6, 2015, researchers and health professionals from 13 countries (Argentina, Brazil, Colombia, French Guiana, Guatemala, Guyana, Mexico, Panama, Surinam, Trinidad and Tobago, the United Kingdom, the United States, and Venezuela), representing organizations including the Pan American Health Organization, the US Centers for Disease Control and Prevention, the Foundation for Scientific Research of Suriname, and the Institut National de la Sante et de la Recherche Medicale, met in Paramaribo, Suriname, to define the next steps necessary to fight disseminated histoplasmosis in HIV patients (Figure).

SU-E-T-565: RAdiation Resistance of Cancer CElls Using GEANT4 DNA: RACE

Purpose: The objective of the RACE project is to develop a comparison between Monte Carlo simulation using the Geant4-DNA toolkit and measurements of radiation damage on 3D melanoma and chondrosarcoma culture cells coupled with gadolinium nanoparticles. We currently expose the status of the developments regarding simulations. Methods: Monte Carlo studies are driven using the Geant4 toolkit and the Geant4-DNA extension. In order to model the geometry of a cell population, the opensource CPOP++ program is being developed for the geometrical representation of 3D cell populations including a specific cell mesh coupled with a multi-agent system. Each cell includes cytoplasm and nucleus. The correct modeling of the cell population has been validated with confocal microscopy images of spheroids. The Geant4 Livermore physics models are used to simulate the interactions of a 250 keV X-ray beam and the production of secondaries from gadolinium nanoparticles supposed to be fixed on the cell membranes. Geant4-DNA processes are used to simulate the interactions of charged particles with the cells. An atomistic description of the DNA molecule, from PDB (Protein Data Bank) files, is provided by the so-called PDB4DNA Geant4 user application we developed to score energy depositions in DNA base pairs and sugar-phosphate groups. Results: At the microscopic level, our simulations enable assessing microscopic energy distribution in each cell compartment of a realistic 3D cell population. Dose enhancement factors due to the presence of gadolinium nanoparticles can be estimated. At the nanometer scale, direct damages on nuclear DNA are also estimated. Conclusion: We successfully simulated the impact of direct radiations on a realistic 3D cell population model compatible with microdosimetry calculations using the Geant4-DNA toolkit. Upcoming validation and the future integration of the radiochemistry module of Geant4-DNA will propose to correlate clusters of ionizations with in vitro experiments. All those developments will be released publicly. This work was supported by grants from Plan Cancer 2009-2013 French national initiative managed by INSERM (Institut National de la Sante et de la Recherche Medicale)

Key issues in evolving dementia care: international theory-based policy and practice

Foreword, Professor June Andrews, Director, Dementia Services Development Centre, University of Stirling, Scotland. Introduction. Part I. Conceptualising Dementia. 1. Towards a Holistic Approach for Understanding Dementia, Anthea Innes, Senior Lecturer in Dementia Studies, School of Applied Social Science, University of Stirling, Scotland. 2. Developing Evidence for Action: Dementia Care in Canada, Scott Dudgeon, Chief Executive Officer, Alzheimer Society of Canada. 3. Epidemiology: An Overview of Current and Predicted Epidemiological Factors Shaping Dementia Care, Nicola Coley, Postdoctoral researcher, Institut National de la Sante et de la Recherche Medicale (INSERM)-Toulouse III University UMR1027, Department of Epidemiology and Public Health, Toulouse University Hospital, France Claudine Berr, INSERM research Director, INSERM-Montpellier University Research Unit UMR1061, Department of Neurology, Montpellier University Hospital, France and Sandrine Andrieu, Professor of Epidemiology and Public Health, INSERM-Toulouse III University UMR1027, Department of Epidemiology and Public Health, Toulouse University Hospital, France. 4. Integrated Care and Treatment of Dementia: Defining Best Practice for the Twenty-first Century, Laura Telford, foundation year doctor in geriatric medicine, Victoria Hospital, Kirkaldy, Scotland Emily Gallagher, foundation year doctor in geriatric medicine, Victoria Hospital, Kirkaldy, Scotland and Emma Reynish, Consultant Physician in Internal Medicine and Geriatrics, Victoria Hospital, Kirkcaldy, Scotland and Honorary Professor in Dementia Studies, University of Stirling, Scotland. Part II. Policy Development. 5. Policy to Enable People with Dementia to Live Well with Dementia: Development of the National Dementia Strategy for England, Sube Banerjee, Professor of Mental Health and Ageing, Institute of Psychiatry, King's College London, England. 6. Three Alzheimer Plans in France (2008-2012), Marie-Jo Guisset Martinez, Programmes Manager, Fondation Mederic Alzheimer, France. 7. Implementing a Regional Strategy: The Fife Dementia Strategy, Louise McCabe, Lecturer in Dementia Studies, School of Applied Social Science, University of Stirling, Scotland. 8. Challenges of Developing a Dementia Strategy: The Case of Malta, Charles Scerri, Lecturer in Neuropathology and Neuropsychopharmacology, University of Malta. Part III. Innovative Approaches to Care. 9. The Function of Memory Clinics and Post-diagnostic Services for People Newly-diagnosed with Dementia and their Families, Fiona Kelly, Lecturer in Dementia Studies, School of Applied Social Science, University of Stirling, Scotland and Paulina Szymczynska, Research Associate, Dementia Services Development Centre, University of Stirling, Scotland. 10. Bridging the Gap for Dementia Care in India, Amit Dias, Assistant Professor, Department of Preventive Medicine, Goa Medical College, India. 11. Evaluating the Impact of Environmental Design Features on Physical Activity Levels of Individuals with Dementia Living in Residential Accommodation, Loren deVries, Transitional Nurse Practitioner, The Garrawarra Centre, New South Wales, Australia and Victoria Traynor, Associate Professor, School of Nursing, Midwifery and Indigenous Health, Australia. 12. Innovative Dementia Training in the Deep South of the United States, Christopher Jay Johnson, PhD, retired Professor, Family Therapist and Researcher and Roxanna H. Johnson, Aging Consultants, Inc., USA. Conclusion. The Contributors. Subject Index. Author Index.

Correction: Modulation of Malaria Infection in Anopheles gambiae Mosquitoes Exposed to Natural Midgut Bacteria

There were multiple errors in the second paragraph of the Effect of bacterial challenge on P. falciparum development section of the Results: When efficacy was measured as changes in oocyst intensity, the bacterial challenge had no effect irrespective of the oocyst intensity in the control group (Figure 3C). However, the reduction in oocyst prevalence due to the bacterial exposure was lower when parasite exposure was higher – in feedings that gave rise to the highest oocyst intensities in the PBS control, the bacterial challenge had almost no effect (Figure 3B). In addition, an affiliation of the ninth author is missing: In addition to institution number 7, Antoine Berry is also affiliated with the the following institution: Centre de Physiopathologie de Toulouse-Purpan, Institut National de la Sante et de la Recherche Medicale, UMR1043, CNRS UMR5282, Universite de Toulouse Paul Sabatier, Toulouse, France.

Correction: Potential Role of Estrogen Receptor Beta as a Tumor Suppressor of Epithelial Ovarian Cancer

There was an error in the Funding statement. The correct statement is: This work was supported by grants from ARC (Association pour la Recherche contre le Cancer, Grant No. 3582) (http://www.arc-cancer.net), The Ligue Nationale Contre le Cancer (http://www.ligue-cancer.net). Muriel Busson was supported by FRM (Fondation pour la Recherche Medicale) (http://www.frm.org). DV was a recipient of the Ligue Nationale contre le Cancer. CB was supported by a HFSP fellowship (http://www.hfsp.org/). The K. B. lab is supported by the Agence Nationale de la Recherche (ANR, grant number 2010 JCJC 1104 01) (http://www.agence-nationale-recherche.fr ​/), the Universite Paris-Sud, the Institut National de la Sante et de la Recherche Medicale (INSERM) and the Ligue Nationale Contre le Cancer (Comite Val d'Oise), and is a member of the Laboratory of Excellence LERMIT (Laboratory of Excellence in Research on Medication and Innovative Therapeutics) supported by a grant from ANR (Investissements d´Avenir). Dr Madly Brigitte was supported by the Fondation ARC and Dr Carine Jacquard by INCA (Institut National du Cancer). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Gut microbiota and metabolic diseases: myth or reality?

Microorganisms inhabiting human gastro-intestinal tract exceed the overall number of eukaryotic cells of about one order of magnitude [1–4]. Among the estimated 500–1,000 species [3], the majority has an unknown function, is neither beneficial nor harmful to host and represents the so-called ‘‘normal flora’’ or ‘‘microbiota’’ [5]. Noteworthy, the development of ‘‘next-generation’’ sequencing techniques, as part of the so-called ‘‘Omics’’, provided an holistic investigation allowing the study of the totality of gut microbiota, avoiding the need for lab-cultivation. These new molecular approaches opened the route toward a deeper investigation of the relationship between gut microbiota and host metabolism, focusing on multiple sides. Nowadays, Metagenomics [6, 7], Metatranscriptomics, Metabolomics [8] and Proteomics [9, 10] allow the study of gut microbiota genome, transcriptome and its impact on host metabolic profiles, respectively. In the last decade, an increasing attention has been paid on gut microbiota, given its involvement in functions other than digestion, as the etiology of inflammatory bowel diseases [11–13], autoimmunity [14–16], allergy [17] and even cancer [2]. However, the inner relationship between gut microbiota and host metabolism has been extensively investigated especially focusing on metabolic diseases [5, 18], even if the molecular actors underlying this inner link are yet to be fully understood. Gordon’s team performed pioneering studies using axenic (germfree) mice as a powerful model to study the impact of gut microbiota. Albeit these mice represent a non-physiologic model since the lack of gut microbiota impairs gut physiology [19], it has been shown that the establishment of a gut flora by colonization of axenic recipient mice with gut microbiota from donor mice is able to reverse this phenotype [20]. In addition, axenicity makes these mice resistant to dietinduced obesity, through a mechanism involving the enzyme lipoprotein lipase (LPL) and its inhibitor, the intestinal Fasting-induced adipocyte factor (Fiaf), which is over-activated in germfree conditions. This results in a diminished capacity to harvest energy from nutrients [21]. Gut microbiota ecology has been shown as deeply unbalanced in relation to metabolic diseases and on the top of it, obesity. The division of Firmicutes, a major phylum of gut microbiota in adulthood [22], has been positively correlated to body weight gain and obesity [23, 24]. Conversely, the division of Bacteroidetes, the second most represented phylum of gut bacterial ecology, characterizes a lean phenotype, both in humans and mice [23, 24]. Gordon’s team was even the first to show the transmissibility of obesity by transferring its microbial component (gut microbiota issued from obese mice) into axenic recipient and showing an increased adipose tissue development when compared to recipient mice colonized with gut microbiota issued from lean mice [25]. However, metabolic diseases are always associated with a low-grade chronic inflammation in metabolically active tissues [26, 27]. Therefore, in the quest of a missing link between gut microbiota and inflammation, Burcelin’s team was the first to link inflammation to intestinal microbiota and metabolic diseases by showing that an increase in lipopolysaccharides (LPS) plasma levels (referred to as ‘‘metabolic endotoxemia’’) was the initiator of metabolic M. Serino (&) R. Burcelin Institut National de la Sante et de la Recherche Medicale (INSERM), U858, Toulouse, France e-mail: matteo.serino@inserm.fr

HUPO’s Effort To Define the Liver Proteome

HUPO’s Effort To Define the Liver Proteome

Erratum

Torgovnik and colleagues' letter offers us the opportunity to clarify some of our results. Torgovnik and colleagues state that the number of patients included in our study1 was small, and that some recovered with placebo, whereas others did not respond to botulinum toxin type A (BTX-A). We would counter that the results of our controlled and blinded study were straightforward on most outcomes. We also acknowledge that large samples are generally needed to achieve significance in pharmacological studies of neuropathic pain.2 The recovery observed in a few placebo-treated patients is in keeping with generally high placebo effects in neuropathic pain.3 The fact that BTX-A was poorly effective in some patients is consistent with meta-analyses showing that the proportion of responders to antineuropathic drugs generally does not exceed 30%.2 Interestingly, the effects of BTX-A were inversely correlated to the severity of thermal deficits (eg, nonresponders had more severe nociceptive fiber impairment than those who responded well to treatment),1 which constitutes a first step toward identifying responder profiles to BTX-A. Torgovnik and colleagues state that the evidence for efficacy of BTX-A is not infallible in neuropathic pain and migraine. Disparate findings were, indeed, reported with BTX-A in migraine in several class I trials4; however, our study is the first class I trial showing efficacy in painful focal neuropathies. The results obtained with BTX-A in migraine, the mechanism of which bears little similarity to that of neuropathic pain, cannot preclude efficacy in neuropathic pain. More generally, Torgovnik and colleagues appear to address the relevance of evidence-based medicine; however, well-conducted, randomized, placebo-controlled trials are crucially needed in neuropathic pain and have notably contributed to the disregard of various ineffective treatments, such as benzodiazepines and sympatholytics.2 Although we acknowledge that further trials are necessary to expand indications for botulinum toxin to other types of neuropathic pain and to better understand its mechanisms of action, we believe that our study offers promising new therapeutic perspectives for botulinum toxin.5 The last comment from Torgovnik and colleagues concerns our relationship with Allergan. On one occasion in 2004, Danièle Ranoux received an honorarium from Allergan in the amount of 2,500 euros for an educational program regarding the respective potencies of botulinum toxin (Botox) and BTX-A (Dysport) on muscle tone.6 The last contact she had with Allergan was in 2006 concerning a study of the clinical differences between various botulinum toxin formulations, which was published in a supplemental issue of European Journal of Neurology,7 sponsored by an unrestricted education grant from Allergan.7 Dr Ranoux did not receive honoraria for this publication. Although we mentioned in our article1 that Allergan supplied the BTX-A that was used in the study, we neglected to disclose this previous relationship with Allergan because the honorarium in question was totally unrelated to the study published in Annals, and we do not believe that this past relationship could constitute a potential conflict of interest or source of bias for the current study, which used an appropriately controlled and blinded design. To be clear, we did not receive support from Allergan in any aspect (ie, financial, study design, statistical analysis, manuscript writing, or data management) for the study published in Annals,1 which was made possible through a collaboration between Danièle Ranoux, a botulinum toxin specialist, and Institut National de la Sante et de la Recherche Médicale neurologists and pain specialists. Editors note: The editors recognize that standards for disclosures of potential conflicts of interest cannot be codified easily to fit all possible situations; however, we have initiated a policy requiring acknowledgment of all financial ties to forprofit organizations whose products are in any way related to the study submitted to Annals. The editors consider any such relationship a conflict of interest if it took place within 2 years of the initiation of the study.