30 research outputs found

    Prevalence and phenotypic features of polycystic ovary syndrome among patients attending gynaecology clinic in two referral hospitals in Yaoundé, Cameroon

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    Background: Polycystic ovary syndrome (PCOS) is a common gynaecological endocrine disease in women at reproductive age. This study aimed to determine the prevalence and phenotypes of PCOS among women attending gynecology clinic at the two referral hospitals in Yaoundé.Methods: It was a cross sectional retrospective study involving women attending the gynecology clinic of two referral hospitals in Yaoundé, Cameroon from January 2016 to March 2018. The socio-demographic information, clinical and laboratory characteristics of each patient were collected from the medical files.Results: A total of 143 patients diagnosed with PCOS were included. The prevalence of PCOS was estimated at 3.5%. The mean age of patients was 29.18±4.5 years with a range of 17 to 41 years. Most patients were either overweight (31.7%) or obese (43%) and 0.7% patients were underweight. The most frequent presentations of PCOS patients were infertility (74.1%), oligomenorrhea/amenorrhea (68.5%), hirsutism (62,9%) and acne (20.3%). The different phenotypes represented were classical phenotype A: 69% (99/143), phenotype B: 17% (24/143), phenotype C: 09% (13/143) and phenotype D: 05% (07/143). Medical treatment (76.9%) and general measures (23.1%) were the most frequent therapeutic options among PCOS patients. In vitro fertilization (08.4%) and surgical drilling (07%) was also used.Conclusions: Prevalence of PCOS in our setting is 3.5%. The classical phenotype A is the most common. It is important to think about PCOS in women attending gynecology clinic

    Defining single molecular forces required for Notch activation using nano yoyo

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    Notch signaling, involved in development and tissue homeostasis, is activated at the cell-cell interface through ligand-receptor interactions. Previous studies have implicated mechanical forces in the activation of Notch receptor upon binding to its ligand. Here we aimed to determine the single molecular force required for Notch activation by developing a novel low tension gauge tether (LTGT). LTGT utilizes the low unbinding force between single-stranded DNA (ssDNA) and E. coli ssDNA binding protein (SSB) (~4 pN dissociation force at 500 nm/s pulling rate). The ssDNA wraps around SSB and, upon application of force, unspools from SSB, much like the unspooling of a yoyo. One end of this nano yoyo is attached to the surface though SSB while the other end presents a ligand. A Notch receptor, upon binding to its ligand, is believed to undergo force-induced conformational changes required for activating downstream signaling. If the required force for such activation is larger than 4 pN, ssDNA will unspool from SSB and downstream signaling will not be activated. Using these LTGTs, in combination with the previously reported TGTs that rupture double stranded DNA at defined forces, we demonstrate that Notch activation requires forces between 4-12 pN, assuming an in vivo loading rate of 60 pN/s. Taken together, our study provides a direct link between single-molecular forces and Notch activation

    Structural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent TLR4 signaling

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    Toll-like receptor (TLR) signaling is a key innate immunity response to pathogens. Recruitment of signaling adapters such as MAL (TIRAP) and MyD88 to the TLRs requires Toll/interleukin-1 receptor (TIR)-domain interactions, which remain structurally elusive. Here we show that MAL TIR domains spontaneously and reversibly form filaments in vitro. They also form cofilaments with TLR4 TIR domains and induce formation of MyD88 assemblies. A 7-Å-resolution cryo-EM structure reveals a stable MAL protofilament consisting of two parallel strands of TIR-domain subunits in a BB-loop-mediated head-to-tail arrangement. Interface residues that are important for the interaction are conserved among different TIR domains. Although large filaments of TLR4, MAL or MyD88 are unlikely to form during cellular signaling, structure-guided mutagenesis, combined with in vivo interaction assays, demonstrated that the MAL interactions defined within the filament represent a template for a conserved mode of TIR-domain interaction involved in both TLR and interleukin-1 receptor signaling

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

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    Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

    Modelling acid stimulation in the enhanced geothermal system of Soultz-sous-Forêts (Alsace, France)

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    The Soultz-sous-Forêts geothermal plant in northern Alsace (France) is under consideration for a campaign to actively stimulate the low-permeability granitic reservoir. The operation of the enhanced geothermal system requires the re-injection of fluid into the geothermal reservoir, which can cause a strong disequilibrium between the fluid and the granitic rock, as well as the possible dissolution/precipitation of minerals. These mineralogical transformations may have a significant impact on porosity, permeability and fluid pathways in the geothermal reservoir. Various studies have reported that the hydraulic connection between the injection well and the production well is quite poor. Therefore, chemical stimulations are necessary to increase the productivity and injectivity of the Soultz geothermal system. Before performing chemical stimulation in the Soultz geothermal system, a modelling approach is considered to discuss different scenarios in terms of the choice of acid and the amount and duration of acid injection. The approach used in this work is based on the geochemical code KIRMAT, which enables us to represent the geothermal reservoir using single-porosity and double-porosity models. The code evaluates the changes in the porosity and permeability of the Soultz reservoir based on the evolution of all primary and secondary minerals as a function of time in the geothermal system. The modelling results showed that chemical stimulation could significantly increase porosity and perme-ability; however, for both single and double-porosity models, the improved zones are very limited and are only present within a few meters of the reinjection well. The modelling results obtained from the sensitivity case studies showed the significant impact of the Darcy velocity, the initial concentration of the acid used, the duration of the injection and the initial calcite amount, especially in regard to the changes in porosity and the mineralogical transformation of the zone around the acid-injected well. Higher concentrations of the HCl solution also increase the dissolution of primary minerals and then exhibit a stronger porosity increase in the zone around the injection well, but further, precipitation reduces the positive achievements of chemical stimulation

    EX025/2003 1 Face verification using biometric hashing

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    Face-based biometrics approach has proved to be robust and efficient for verification systems (comparison with a reference database). While it opens the door to a range of applications principally aimed at securing areas, it fails to get its way to high-security systems, such as banking transactions. In this thesis, we outline an attempt to take a first step in the latter direction, by generating a unique bit-string per person with an almost error-tolerant transformation of the eigenprojections of a face, from an image processing view point. The discretization is carried out by first projecting the eigencoefficients of the face on a pseudo-random space, then keeping the resulting coordinates that meet a discriminating criterion, and finally deciding each bit on the sign of each selected coordinate. This pseudo-random sequence can be provided by a physical token. In the end, some experiments show that a system tolerant of image capture offsets could be built upon our results, opening the way to possible applications of interest in the cryptographic field

    Performance et équilibre de vie. Les environnements sportifs favorables à la performance paralympique.

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    Le projet ANR PARAPERF « Optimisation de la performance paralympique :de l’identification à l’obtention de la médaille » issu de l’appel à projets ProgrammesPrioritaires de Recherche Sport de Très Haute Performance, a pour objectifde comprendre les enjeux spécifiques de la très haute performance paralympiqueselon les trajectoires de performance, le matériel sportif et l’environnementdes sportifs paralympiques.Ce projet inclut 13 laboratoires de recherche et deux fédérations sportives partenaires,la Fédération Française Handisport (FFH) et la Fédération Française de Tir (FFTir).Dans le cadre d’une mutualisation avec une partie du travail de thèsede Valentine Duquesne, le Comité Paralympique et Sportif Français (CPSF) est égalementpartenaire de la recherche présentée ici.Ce rapport présente certains résultats du lot de travail 3 « Environnementset parcours des parasportifs » qui vise spécifiquement à décrire les conditionsde préparation socio-environnementales, psychologiques et juridiquesdes parasportifs, et d’identifier les conditions les plus propices à la hauteperformance paralympique.Ce rapport a bénéficié des échanges avec certains acteurs du monde paralympique(cadres fédéraux, entraîneurs et parasportifs) survenus lors des ateliers du 10 mai 2022.Pour réaliser ce travail, trois approchesscientifiques ont été mobiliséesde manière complémentaire :la sociologie, la psychologie et le droit.L’enquête sociologique a été réaliséeen deux temps. :La première partie était centrée surl’administration de deux questionnaires,l’un destiné aux parasportifs et l’autreaux acteurs qui les accompagnent.La deuxième partie a consisté en laréalisation de 57 entretiens auprès desparasportifs, des membres de leur staffet parfois de leur famille.La recherche en psychologie s’estdéroulée quant à elle en trois étapes :d’abord la passation de 15 entretiensavec des parasportifs, puis la passationd’un questionnaire auprès de92 parasportifs, et enfin la réalisationd’une série d’entretiens individuelset collectifs auprès des parasportifs et deleur assistant, guide ou pilote.Pour finir, la recherche juridique s’estappuyée sur 34 entretiens réalisés auprèsdes parasportifs, des assistants, guideset pilotes mais aussi auprès des acteurset experts du monde paralympique(notamment les entraîneurs, les headcoacheset les responsables de laperformance).Pour conclure cette partie introductive,il est important de préciser que tout aulong de ce rapport, nous ferons référenceà différents niveaux de performance desparasportifs. En sociologie, la qualificationdes niveaux de performance desparasportifs a été effectuée en se basantsur le modèle Foundation – Talent – Elite –Mastery (modèle FTEM) fondé par l’InstitutAustralien du Sport (AIS) qui caractérisela performance sportive suivant plusieursstades de développement :Le stade Fondation (Foundation)correspond à l’acquisition desfondamentaux relatifs aux disciplinessportives.Le stade Talent correspondà l’identification par les institutionssportives en charge de la performance,de parasportifs susceptibles de développerdes hauts niveaux de performance à courtou long terme.Le stade Elite correspond auxparasportifs ayant représenté leur paysau sein de compétitions internationaleset éventuellement réalisé des podiums.Le stade Mastercorrespond aux parasportifsmultimédaillés à l’international depuisau moins les quatre dernières années.Il s’agit donc ici de parasportifsqui dominent leur discipline depuisun nombre d’années significatif.En psychologie, la qualification de laperformance a été réalisée via un indicede performance (minimum 0 et maximum34) calculé en fonction des compétitionseffectuées et des résultats qui y ont étéobtenus par les parasportifs
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