Hôpital de Vaugirard-Gabriel Pallez

Drosophila is a powerful model system to study the regulatory and effector mechanisms of innate immunity. To identify molecules induced in the course of viral infection in this insect, we have developed a model based on intrathoracic injection of the picorna-like Drosophila C virus (DCV). We have used MALDI-TOF mass spectrometry to compare the hemolymph of DCV infected flies and control flies. By contrast with the strong humoral response triggered by injection of bacteria or fungal spores, we have identified only one molecule induced in the hemolymph of virus infected flies. This molecule, pherokine-2 (Phk-2), is related to OS-D/A10 (Phk-1), which was previously characterized as a putative odor/pheromone binding protein specifically expressed in antennae. The virus-induced molecule is also similar to the product of the gene CG9358 (Phk-3), which is induced by septic injury. Both Phk-2 and Phk-3 are strongly expressed during metamorphosis, suggesting that they may participate in tissue-remodeling.

BACKGROUND AND AIMS: The importance of the hepatocyte ploidisation pattern to the control of cell proliferation and differentiation has been well established. However, there are no data that have characterised hepatocyte ploidy at various stages of chronic liver inflammation and fibrosis in vivo. METHODS: We therefore investigated hepatocyte ploidy/binuclearity patterns in 57 patients with chronic hepatitis, using a recently developed methodology which allows simultaneous hepatocyte ploidy and binuclearity analyses on the same liver section. RESULTS: The percentage of mononuclear diploid hepatocytes was significantly reduced in patients with high hepatitis activity and marked fibrosis (low activity: 75.1 (18.8)% v high activity: 61.8 (21.6)%, p=0.0111, and low fibrosis: 77.3 (13.8)% v high fibrosis: 57.4 (23.3)%, p=0.0002). Accordingly, the percentage of mononuclear polyploid hepatocytes increased in patients with high hepatitis activity and marked fibrosis (low activity: 11.9 (15.5)% v high activity: 22.2 (20.1)%, p=0.0166, and low fibrosis: 9.4 (10.7)% v high fibrosis: 26.4 (21.6)%, p=0.0001). In addition, the fraction of binuclear hepatocytes was significantly higher in patients with hepatitis B virus (HBV) than in those with hepatitis C virus (HCV) infections (HBV: 18.2 (7.6)% v HCV: 12.0 (4.8)%; p=0.0020). Under multivariate analysis, HBV infection was an independent factor accounting for the larger binuclear hepatocyte fraction (p=0.0294). CONCLUSION: Our results revealed an increase in the polyploid hepatocyte fraction which correlates with the severity of chronic hepatitis; moreover, we demonstrated that HBV and HCV related chronic hepatitis exhibited distinctive hepatocyte ploidy patterns, thus allowing the suggestion that these two viral infections may modulate liver ploidy through different mechanisms.

The role of the hepatitis B virus X protein (HBx) in the pathogenesis of hepatitis B virus (HBV) infection remains unclear. HBx exhibits pleiotropic biological effects, whose in vivo relevance is a matter for debate. In the present report, we have used a combination of HBx-expressing transgenic mice and liver cell transplantation to investigate the in vivo impact of HBx expression on liver cell proliferation and viability in a regenerative context. We show that moderate HBx expression inhibits liver regeneration after partial hepatectomy in HBx-expressing transgenic mice. We also demonstrate that the transplantation of HBx-expressing liver cells, isolated from HBx transgenic mice, is sufficient to inhibit overall recipient liver regeneration after partial hepatectomy. Moreover, the injection of serum samples drawn from HBx-expressing transgenic mice mimicked the inhibitory effect of HBx on liver regeneration. Finally, the incubation of primary rat hepatocytes with the supernatant of HBx-expressing liver cells inhibits cellular DNA synthesis. Taken together, our results demonstrate a paracrine inhibitory effect of HBx on liver cell proliferation and lead us to propose HBV as one of the few viruses implicated in human cancer which act, at least in part, through paracrine biological pathways.

BACKGROUND: Incontinence associated dermatitis (IAD) is an inflammatory skin disease mainly triggered by prolonged skin contact with urine, feces but also liberal detergent use when cleansing the skin. To minimize the epidermal barrier challenge we optimized the design of adult incontinence briefs. In the fluid absorption area we interposed a special type of acidic, curled-type of cellulose between the top sheet in contact with the skin and the absorption core beneath containing the polyacrylate superabsorber. The intention was to minimize disturbance of the already weak acid mantle of aged skin. We also employed air-permeable side panels to minimize skin occlusion and swelling of the stratum corneum. METHODS: The surface pH of diapers was measured after repeated wetting with a urine substitute fluid at the level of the top sheet. Occlusive effects and hydration of the stratum corneum were measured after a 4 hour application of different side panel materials by corneometry on human volunteers. Finally, we evaluated skin symptoms in 12 patients with preexisting IAD for 21 days following the institutional switch to the optimized diaper design. Local skin care protocols remained in place unchanged. RESULTS: The improved design created a surface pH of 4.6 which was stable even after repeated wetting throughout a 5 hour period. The "standard design" briefs had values of 7.1, which is alkaline compared to the acidic surface of normal skin. Side panels made from non-woven material with an air-permeability of more than 1200 l/m2/s avoided excessive hydration of the stratum corneum when compared to the commonly employed air-impermeable plastic films. Resolution of pre-existing IAD skin lesions was noted in 8 out of 12 patients after the switch to the optimized brief design. CONCLUSIONS: An improved design of adult-type briefs can create an acidic pH on the surface and breathable side panels avoid over-hydration of the stratum corneum and occlusion. This may support the epidermal barrier function and may help to reduce the occurrence of IAD.

The current SARS-CoV-2 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID-19 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS-CoV-2 infections may, at least in part, be due also to differences between the viral subspecies with which individuals are infected. A more pertinent question is how we are to overcome the current pandemic. A vaccine against SARS-CoV-2 would offer significant relief, although vaccine developers have warned that design, testing and production of vaccines may take a year if not longer. Vaccines are based on a handful of different designs (i), but the earliest vaccines were based on the live, attenuated virus. As has been the case for other viruses during earlier pandemics, SARS-CoV-2 will mutate and may naturally attenuate over time (ii). What makes the current pandemic unique is that, thanks to state-of-the-art nucleic acid sequencing technologies, we can follow in detail how SARS-CoV-2 evolves while it spreads. We argue that knowledge of naturally emerging attenuated SARS-CoV-2 variants across the globe should be of key interest in our fight against the pandemic.

Plasmacytoid dendritic cells (pDC) are specialized in secretion of type I interferon in response to pathogens. Here we show that natural monoamines and synthetic amines inhibit pDC activation by RNA viruses. Furthermore, a synthetic analogue of histamine reduces type I interferon production in a mouse model of influenza infection. We identify CXC chemokine receptor 4 (CXCR4) as a receptor used by amines to inhibit pDC. Our study establishes a functional link between natural amines and the innate immune system and identifies CXCR4 as a potential 'on-off' switch of pDC activity with therapeutic potential.

Abstract Objective: To compute a risk index for nosocomial infection (NI) surveillance in geriatric long-term-care facilities (LTCFs) and rehabilitation facilities. Design: Analysis of data collected during the French national prevalence survey on NIs conducted in 1996. Risk indices were constructed based on the patient case-mix defined according to risk factors for NIs identified in the elderly. Setting: 248 geriatric units in 77 hospitals located in northern France. Participants: All hospital inpatients on the day of the survey were included. Results: Data from 11,254 patients were recorded. The overall rate of infected patients was 9.9%. Urinary tract, respiratory tract, and skin were the most common infection sites in both rehabilitation facilities and LTCFs. Eleven risk indices, categorizing patients in 3 to 7 levels of increasing NI risk, ranging from 2.7% to 36.2%, were obtained. Indices offered risk adjustment according to NI rate stratification and clinical relevance of risk factors such as indwelling devices, open bedsores, swallowing disorders, sphincter incontinence, lack of mobility, immunodeficiency, or rehabilitation activity. Conclusion: The optimal index should be tailored to the strategy selected for NI surveillance in geriatric facilities in view of available financial and human resources.

PURPOSE: Medicine acceptability, which is of the utmost importance for vulnerable patients' adherence, is driven by both user and product characteristics. Herein, a novel multivariate approach integrating the many aspects of acceptability is used to discriminate positively and negatively accepted medicines in the older population. METHODS: An observational study was carried out in eight hospitals and eight nursing homes to collect a large set of real-life data on medicines uses in older patients (≥65 years). Mapping and clustering explored these multiple observational measures and summarised the main information into an intelligible reference framework. Resampling statistics were used to validate the model's reliability. RESULTS: A three-dimensional map and two clusters defining acceptability profiles, as positive or negative, emerged from the 1079 evaluations. Factors of interest (medicines, user features…) were positioned on the map at the barycentre of their evaluations and assigned to an acceptability profile. Focusing on patients' ability to swallow, we have highlighted the tool's efficacy in demonstrating the impact of user features on medicine acceptability. CONCLUSIONS: This multivariate approach provides a relevant judgement criterion for this multi-dimensional concept. Facilitating the choice of the most appropriate dosage form to achieve optimal acceptability in a targeted population, this tool is of real potential to improve clinical decisions.

BACKGROUND: The dynamics of SARS-CoV-2 alpha variant shedding and immune responses at the nasal mucosa remain poorly characterised. METHODS: We measured infectious viral release, antibodies and cytokines in 426 PCR+ nasopharyngeal swabs from individuals harboring non-alpha or alpha variants. FINDINGS: infectious units. Rapid antigenic diagnostic tests were positive in 94% of samples with infectious virus. 68 % of individuals carried infectious virus within two days after onset of symptoms. This proportion decreased overtime. Viable virus was detected up to 14 days. Samples containing anti-spike IgG or IgA did not generally harbor infectious virus. Ct values were slightly but not significantly lower with alpha. This variant was characterized by a fast decrease of infectivity overtime and a marked release of 13 cytokines (including IFN-b, IP-10 and IL-10). INTERPRETATION: The alpha variant displays modified viral decay and cytokine profiles at the nasopharyngeal mucosae during symptomatic infection. FUNDING: This retrospective study has been funded by Institut Pasteur, ANRS, Vaccine Research Institute, Labex IBEID, ANR/FRM and IDISCOVR, Fondation pour la Recherche Médicale.

Research Articles| June 18 2008 ARCHITECTURE MUSCULAIRE DE LA JUNCTION CHOLÉDOCO-PANCRÉATICO- DUODÉNALE Subject Area: Further Areas , Pathology and Cell Biology M. Papamiltiades; M. Papamiltiades Laboratoire de la Chaire d'Anatomie de la Faculté de Médecine de Paris (Prof. G. Cordier) et laboratoire de chirurgie expérimentale (Prof. agr. Marcel Roux) de la Clinique Thérapeutique chirurgicale de ΓHôpital de Vaugirard (Prof. J. Sénèque) Search for other works by this author on: This Site PubMed Google Scholar R. Rettori R. Rettori Laboratoire de la Chaire d'Anatomie de la Faculté de Médecine de Paris (Prof. G. Cordier) et laboratoire de chirurgie expérimentale (Prof. agr. Marcel Roux) de la Clinique Thérapeutique chirurgicale de ΓHôpital de Vaugirard (Prof. J. Sénèque) Search for other works by this author on: This Site PubMed Google Scholar Acta Anatomica (1957) 30 (1-4): 575–600. https://doi.org/10.1159/000141230 Article history Published Online: June 18 2008 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation M. Papamiltiades, R. Rettori; ARCHITECTURE MUSCULAIRE DE LA JUNCTION CHOLÉDOCO-PANCRÉATICO- DUODÉNALE. Acta Anatomica 31 December 1957; 30 (1-4): 575–600. https://doi.org/10.1159/000141230 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsActa Anatomica Search Advanced Search Article PDF first page preview Close Modal This content is only available via PDF. 1957Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. You do not currently have access to this content.

Relations between sensory functions and Alzheimer's disease are still under-explored. To understand them better, the Fondation Médéric Alzheimer has brought together a multi-disciplinary expert group. Aristote's five senses must be enhanced by today's knowledge of proprioception, motor cognition and pain perception. When cognition breaks down, the person with dementia perceives the world around her with her sensory experience, yet is unable to integrate all this information to understand the context. The treatment of multiple sensory inputs by the brain is closely linked to cognitive processes. Sensory deficits reduce considerably the autonomy of people with dementia in their daily life and their relations with others, increase their social isolation and the risk of accidents. Professionals involved with neurodegenerative diseases remain poorly aware of sensory deficits, which can bias the results of cognitive tests. However, there are simple tools to detect these deficits, notably for vision, hearing and balance disorders, which can be corrected. Many interventions for cognitive rehabilitation or quality of life improvement are based on sensory functions. The environment of people with dementia must be adapted to become understandable, comfortable, safe and eventually therapeutic.

Leptin acts on the hypothalamus to reduce food intake and on a number of non-neuronal tissues via specific receptors (Lepr). The use of in situ hybridisation to map the Lepr gene in pre-natal mice revealed transcripts in the yolk sac in various structures of the central nervous system and in mesoderm-derived tissues, such as cartilage/bone primordia and musculoaponeurotic laminae. At later stages, significant amounts of Lepr were expressed in the region surrounding the developing eye of the embryo. Lepr was also found to be expressed in the choroid, sclera and connective tissues of the limbus in the adult eye. In conclusion, we have identified new targets for leptin action during embryogenesis and adulthood.

We derive an asymptotic expansion for the distribution of a compound sum of independent random variables, all having the same rapidly varying subexponential distribution. The examples of a Poisson and geometric number of summands serve as an illustration of the main result. Complete calculations are done for a Weibull distribution, with which we derive, as examples and without any difficulties, seven-term expansions.

Abstract The mechanisms that allowed for the SARS-CoV-2 B.1.1.7 variant to rapidly outcompete pre-existing variants in many countries remain poorly characterized. Here, we analyzed viral release, anti-SARS-CoV-2 antibodies and cytokine production in a retrospective series of 427 RT–qPCR+ nasopharyngeal swabs collected in COVID-19 patients harbouring either non-B.1.1.7 or B.1.17 variants. We utilized a novel rapid assay, based on S-Fuse-T reporter cells, to quantify infectious SARS-CoV-2. With both non-B.1.1.7 and B.1.1.7 variants, viral titers were highly variable, ranging from 0 to >10 6 infectious units, and correlated with viral RNA levels. Lateral flow antigenic rapid diagnostic tests (RDTs) were positive in 96% of the samples harbouring infectious virus. About 67 % of individuals carried detectable infectious virus within the first two days after onset of symptoms. This proportion decreased overtime, and viable virus was detected up to 14 days. Samples containing anti-SARS-CoV-2 IgG or IgA did not generally harbour infectious virus. The proportion of individuals displaying viable virus or being RDT-positive was not higher with B.1.1.7 than with non-B.1.1.7 variants. Ct values were slightly but not significantly lower with B.1.1.7. The variant was characterized by a fast decrease of infectivity overtime and a marked release of 17 cytokines (including IFN-β, IP-10, IL-10 and TRAIL). Our results highlight differences between non-B.1.1.7 and B.1.1.7 variants. B.1.1.7 is associated with modified viral decays and cytokine profiles at the nasopharyngeal mucosae during symptomatic infection.

In the context of therapeutic education for people living with HIV in Africa, educational tools must be adapted to their living environment. OBJECTIVES: To describe the process of designing education tools for patients living with HIV and evaluate their use by African caregivers-educators. METHODS: An eight-step participatory and formative process was carried out to design educational tools. Twenty-one caregivers-educators from nine French-speaking African countries in three focus groups were interviewed on the way in which they used these tools. RESULTS: Fourteen people were trained in the process of designing the tools and training caregivers-educators in their use. Two toolkits were developed (adults and children/adolescents). The image folder was the tool most commonly used. Educators in all countries used tools to address self-care and psychosocial coping skills. The criteria for choosing the tools were linked to their attractiveness, ease of use, their adaptation to the patient's needs and characteristics, and the degree of mastery by the caregiver-educator. The tools helped to structure the education sessions. Brakes to their use were organizational and lack of experience or mastery. CONCLUSION: The participatory and formative approach enabled educators working with patients living with HIV in French-speaking Africa to appropriate the tools. Training was a crucial step in enabling caregiver-educators to master and disseminate the tools, and design new tools.

Le rêve-éveillé en psychothérapie psychanalytique demeure fidèle à l’inspiration première de Desoille qui fut le créateur du rêve-éveillé-dirigé. Dans les cures où le problème familial est au centre de la problématique, il joue son rôle de parole métaphorique. Grâce à lui, l’indicible peut se vivre, se dire et se résoudre. Il est aussi chemin vers le secret de famille pressenti et peu à peu dévoilé ou arraché au fantasme. Ces thèmes seront développés à travers trois exemples cliniques.

Dans les livres pour enfants, curieusement, les références culturelles abondent — au moins autant qu'en littérature générale, tant pour des raisons didactiques que parce que l'humour et la complicité, leurs ingrédients premiers, se nourrissent de sous-entendus. Ce qui n'en facilite pas la traduction, le jeune lecteur de la culture d'accueil disposant, sur la culture d'origine, d'un bagage de références plus léger encore que l'adulte. Difficulté qui culmine avec le dilemme des allusions. Comment préserver à l'implicite son statut et sa saveur d'implicite ? Comment naviguer entre ces deux écueils : le risque de produire un texte sybillin qui découragera le jeune lecteur, et celui de surexpliciter, qui privera le texte traduit d'une dimension essentielle, son étrangeté — ou, dans le cas d'un texte fort étrange lui-même à sa propre culture, sa double étrangeté ?

Des formes faciles à observer, cannelures de puits et cannelures glaciaires de paroi dans les grottes, cannelures nivales et pluviales dans les lapiaz, lapiaz à tétraèdres, rigoles de karst semi-couvert et lapiaz à rigoles et bourrelets, sont des indicateurs climatiques. Les variations climatiques ont modifié leurs relations mutuelles, ainsi qu’avec d’autres formes de lapiaz ou de relief.

We derive an asymptotic expansion for the distribution of a compound sum of independent random variables, all having the same rapidly varying subexponential distribution. The examples of a Poisson and geometric number of summands serve as an illustration of the main result. Complete calculations are done for a Weibull distribution, with which we derive, as examples and without any difficulties, seven-term expansions.

(1) Background/Objectives: Human papillomavirus (HPV) testing is hypothesised to detect cervical intraepithelial neoplasia grade 3 (CIN3) earlier than cervical cytology, which could translate into several clinical benefits. This study aimed to confirm that HPV testing detects CIN3 lesions of smaller size (or linear extension) and to assess whether this is associated with a decreased risk of stromal microinvasion (≤3 mm) (microinvasive or stage IA1 cervical carcinoma). (2) Methods: The study was conducted in a referral centre for cervical pathology in Italy. Eligible were 3744 patients aged 30–64 years who underwent local excision of the cervix between 1992 and 2021 and were diagnosed with CIN3, with or without microinvasion. Data were analysed using logistic and multinomial regression models. (3) Results: Overall, 1156 (30.9%) CIN3 cases were detected by the HPV test, and 2588 (69.1%) by cervical cytology. The lesion size was smaller in HPV test-detected CIN3 (median, 6 mm; interquartile range (IQR), 4–8 mm) than in cytology-detected CIN3 (median, 7 mm; IQR, 5–9 mm; p < 0.001). HPV test-detected CIN3 was over 50% less likely to have a size >6 mm combined with massive glandular crypt involvement. Stromal microinvasion occurred in 20/1156 (1.7%) HPV test-detected lesions versus 87/2588 (3.4%) cytology-detected lesions (p = 0.006), corresponding to an approximately 50% lower age-adjusted risk. The smaller size of HPV test-detected CIN3 and its lower degree of glandular crypt involvement interacted additively, rather than multiplicatively, in reducing the risk of stromal microinvasion. Over 46% of the association between detection mode and stromal microinvasion was explained by the size/involvement composite variable. (4) Conclusions: HPV testing detects CIN3 lesions of smaller size than cervical cytology. HPV test-detected CIN3 has a lower risk of stromal microinvasion. This association is mediated to a substantial extent by the smaller lesion size and the less extensive glandular crypt involvement, which interact in an additive manner. These findings may have other important clinical implications. First, the prevalence of disease persistence after treatment may decrease. Second, smaller lesions are likely to be treated with more limited excisions. Third, this may contribute to a lower rate of preterm birth in subsequent pregnancies.