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"Fourn"
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Une vie mouvementée. Approche biographique du conflit syrien, de la révolution à l’exil
by
Fourn, Léo
2024
Cet article aborde les événements historiques qui secouent la Syrie depuis 2011 à partir d’une approche biographique. En analysant le parcours de Ghania, militante engagée pour la révolution depuis 2011 exilée en France, il cherche à interroger les incidences de la participation à ces événements. Il met ainsi en exergue le rôle des bifurcations ponctuant son parcours en s’efforçant de déceler leurs effets socialisateurs. Il montre qu’en participant au soulèvement, Ghania a connu un processus de subjectivation politique et a intériorisé de nouvelles dispositions. Ces dispositions sont observables dans sa participation prolongée à des actions collectives, plus particulièrement dans son engagement pour la cause des femmes, ainsi qu’à travers sa pratique du témoignage public. Quoique fragilisées par la défaite et l’exil, les incidences de sa participation à la révolution syrienne se révèlent durables. This article adopts a biographical approach to the historical events that have shaken Syria since 2011. By analyzing the path of Ghania, an activist involved in the revolution since 2011 exiled in France, it seeks to question the impact of her participation in these events. It highlights the role of the turning points that punctuate her path and seeks to identify their socializing effects. By participating in the uprising, Ghania experienced a process of political subjectivation and interiorized new dispositions. These dispositions can be observed in her sustained participation in collective actions, particularly in her commitment to the women’s cause, as well as through her practice of public testimony. Although undermined by defeat and exile, the consequences of her participation in the Syrian revolution proved long-lasting.
Journal Article
Protein N-glycosylation, protein folding, and protein quality control
by
Park, S.J., Yonsei University, Seoul, Republic of Korea
,
Kysela, Katarina Gaplovska, University of Zurich, Zurich, Switzerland
,
Lee, Y.S., Yonsei University, Seoul, Republic of Korea
in
Biochemistry
,
Biomedical and Life Sciences
,
Biomedicine
2010
Quality control of protein folding represents a fundamental cellular activity. Early steps of protein N-glycosylation involving the removal of three glucose and some specific mannose residues in the endoplasmic reticulum have been recognized as being of importance for protein quality control. Specific oligosaccharide structures resulting from the oligosaccharide processing may represent a glycocode promoting productive protein folding, whereas others may represent glyco-codes for routing not correctly folded proteins for dislocation from the endoplasmic reticulum to the cytosol and subsequent degradation. Although quality control of protein folding is essential for the proper functioning of cells, it is also the basis for protein folding disorders since the recognition and elimination of non-native conformers can result either in loss-of-function or pathological-gain-of-function. The machinery for protein folding control represents a prime example of an intricate interactome present in a single organelle, the endoplasmic reticulum. Here, current views of mechanisms for the recognition and retention leading to productive protein folding or the eventual elimination of misfolded glycoproteins in yeast and mammalian cells are reviewed.
Journal Article
COVID-19 Vaccine Hesitancy among French People Living with HIV
by
Majerholc, Catherine
,
Vallée, Alexandre
,
Zucman, David
in
Acceptance tests
,
Chronic illnesses
,
Coronaviruses
2021
People living with HIV are a high-risk population concerning the coronavirus 19 (COVID-19) infection, with a poorer prognosis. It is important to achieve high COVID-19 vaccination coverage rates in this group as soon as possible. This project used self-reporting to assess vaccine hesitancy and acceptance among people living with HIV towards the novel COVID-19 vaccine. Sixty-eight (28.7%) participants among the 237 declared their hesitancy to be vaccinated against COVID-19. Participants who expressed concerns about their health (p < 0.001), the requirement of mandatory COVID-19 vaccination (p = 0.017), and their chronic disease status (p = 0.026) were independently associated with the acceptance of vaccination. Conversely, participants presenting general vaccine refusal (p < 0.001), concerns about the serious side effects of COVID-19 vaccines (p < 0.001), and those already thinking having an immune status to COVID-19 (p = 0.008) were independently associated with COVID-19 vaccine hesitancy. Our results suggest that vaccine strategy would be more successful in France with a communication strategy emphasizing the collective benefits of herd immunity in the population living with HIV and reassuring patients with chronic diseases about the safety of the proposed vaccines.
Journal Article
Monkeypox Virus Infection in 18-Year-Old Woman after Sexual Intercourse, France, September 2022
2023
A monkeypox virus outbreak has spread worldwide since April 2022. We report a young woman in France positive for monkeypox virus transmitted through oral and vaginal sex. Ulceronecrotic lesions developed intravaginally and around her vulva. Health professionals should become familiar with all aspects of infection from this virus, including possible vertical transmission.
Journal Article
Cleavage-Independent HIV-1 Trimers From CHO Cell Lines Elicit Robust Autologous Tier 2 Neutralizing Antibodies
by
Crispin, Max
,
de Val, Natalia
,
Wilson, Richard
in
Adjuvants
,
Affinity chromatography
,
Antibodies
2018
Native flexibly linked (NFL) HIV-1 envelope glycoprotein (Env) trimers are cleavage-independent and display a native-like, well-folded conformation that preferentially displays broadly neutralizing determinants. The NFL platform simplifies large-scale production of Env by eliminating the need to co-transfect the precursor-cleaving protease, furin that is required by the cleavage-dependent SOSIP trimers. Here, we report the development of a CHO-M cell line that expressed BG505 NFL trimers at a high level of homogeneity and yields of ~1.8 g/l. BG505 NFL trimers purified by single-step lectin-affinity chromatography displayed a native-like closed structure, efficient recognition by trimer-preferring bNAbs, no recognition by non-neutralizing CD4 binding site-directed and V3-directed antibodies, long-term stability, and proper N-glycan processing. Following negative-selection, formulation in ISCOMATRIX adjuvant and inoculation into rabbits, the trimers rapidly elicited potent autologous tier 2 neutralizing antibodies. These antibodies targeted the N-glycan \"hole\" naturally present on the BG505 Env proximal to residues at positions 230, 241, and 289. The BG505 NFL trimers that did not expose V3
, elicited low-to-no tier 1 virus neutralization
, indicating that they remained intact during the immunization process, not exposing V3. In addition, BG505 NFL and BG505 SOSIP trimers expressed from 293F cells, when formulated in Adjuplex adjuvant, elicited equivalent BG505 tier 2 autologous neutralizing titers. These titers were lower in potency when compared to the titers elicited by CHO-M cell derived trimers. In addition, increased neutralization of tier 1 viruses was detected. Taken together, these data indicate that both adjuvant and cell-type expression can affect the elicitation of tier 2 and tier 1 neutralizing responses
.
Journal Article
Monkeypox Vaccine Hesitancy in French Men Having Sex with Men with PrEP or Living with HIV in France
by
Majerholc, Catherine
,
Zucman, David
,
Vallée, Alexandre
in
Antiretroviral drugs
,
Attitudes
,
Disease prevention
2022
People with pre-exposure prophylaxis (PrEP) or living with HIV are a high-risk population for monkeypox virus (MPXV) infection. It is important to achieve high MPXV vaccination coverage rates in this group. This project used self-reporting to assess vaccine hesitancy for the smallpox vaccine and acceptance among men having sex with men with PrEP or living with HIV. In total, 52 (33.6%) participants among the 155 declared their hesitancy to be vaccinated against MPXV. Moreover, 20.7% patients with PrEP declared a hesitant attitude towards the smallpox vaccine compared to 40.2% of the HIV patients, p = 0.013. This difference remained not significant after adjustment for age (p = 0.119) and after adjustment for both age and number of different sexual partners (p = 0.406). Among PrEP people, those who expressed concerns about people getting more vaccines than needed (p = 0.012) were less likely to accept vaccination, whereas an increased number of different sexual partners during the previous month was significantly associated with acceptance of vaccination (p = 0.034). Among HIV people, those who expressed concerns about being infected by MPXV (p < 0.001), those who expressed that the smallpox vaccine should be compulsory for people at risk (p < 0.001) and those with an increased the number of different sexual partners the previous month (p = 0.018) were significantly associated with higher acceptance of MPXV vaccination. Our results suggest that vaccine strategy would be efficient in France with a communication strategy emphasizing the benefits of vaccination and the potential MPXV risk infection for health in PrEP and HIV people. Other preventive actions should be implemented, including reduction in sexual partners.
Journal Article
Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis
by
Schoindre Yoland
,
Chabi Marie-Laure
,
Salvator Hélène
in
C-reactive protein
,
Clinical trials
,
Coronaviruses
2021
BackgroundHigh levels of serum interleukin-6 (IL-6) correlate with disease severity in COVID-19. We hypothesized that tocilizumab (a recombinant humanized anti-IL-6 receptor) could improve outcomes in selected patients with severe worsening COVID-19 pneumonia and high inflammatory parameters.MethodsThe TOCICOVID study included a prospective cohort of patients aged 16–80 years with severe (requiring > 6 L/min of oxygen therapy to obtain Sp02 > 94%) rapidly deteriorating (increase by ≥ 3 L/min of oxygen flow within the previous 12 h) COVID-19 pneumonia with ≥ 5 days of symptoms and C-reactive protein levels > 40 mg/L. They entered a compassionate use program of treatment with intravenous tocilizumab (8 mg/kg with a maximum of 800 mg per infusion; and if needed a second infusion 24 to 72 h later). A control group was retrospectively selected with the same inclusion criteria. Outcomes were assessed at D28 using inverse probability of treatment weighted (IPTW) methodology.ResultsAmong the 96 patients included (81% male, mean (SD) age: 60 (12.5) years), underlying conditions, baseline disease severity, and concomitant medications were broadly similar between the tocilizumab (n = 49) and the control (n = 47) groups. In the IPTW analysis, treatment with tocilizumab was associated with a reduced need for overall ventilatory support (49 vs. 89%, wHR: 0.39 [0.25–0.56]; p < 0.001). Albeit lacking statistical significance, there was a substantial trend towards a reduction of mechanical ventilation (31% vs. 45%; wHR: 0.58 [0.36–0.94]; p = 0.026). However, tocilizumab did not improve overall survival (wHR = 0.68 [0.31–1.748], p = 0.338). Among the 85 (89%) patients still alive at D28, patients treated with tocilizumab had a higher rate of oxygen withdrawal (82% vs. 73.5%, wHR = 1.66 [1.17–2.37], p = 0.005), with a shorter delay before being weaned of oxygen therapy (mean 11 vs. 16 days; p < 0.001). At D28, the rate of patients discharged from hospital was higher in the tocilizumab group (70% vs. 40%, wHR = 1.82 [1.22–2.75]; p = 0.003). The levels of CRP and fibrinogen post therapy (p < 0.001 for both variables) were significantly lower in the tocilizumab group (interaction test, mixed model). Rates of neutropenia (35% vs. 0%; p < 0.001) were higher in the tocilizumab group, yet rates of infections (22% vs. 38%, p = 0.089) including ventilator-acquired pneumonia (8% vs. 26%, p = 0.022) were higher in the control group.ConclusionThese data could be helpful for the design of future trials aiming to counter COVID-19-induced inflammation, especially before patients require admission to the intensive care unit.
Journal Article
De-simplifying single-tablet antiretroviral treatments for cost savings in France: From the patient perspectives to a 6-month follow-up on generics
by
Doisne, Melanie
,
Majerholc, Catherine
,
Giraud, Jean-Stephane
in
Abacavir
,
Acquired immune deficiency syndrome
,
AIDS
2020
In developed countries, most people living with HIV/AIDS are treated with costly brand single-tablet regimens. Given the economic impact, French guidelines recommend using generic antiretroviral therapy when possible to decrease antiretroviral therapy costs. We aimed to study HIV-infected patients' acceptability to switch from a brand single-tablet regimens [abacavir/lamivudine/dolutegravir (Triumeq.sup.®) or emtricitabine/tenofovir disoproxil fumarate/rilpivirine (Eviplera.sup.® )] to a treatment comprising of two pills: one is a fixed-dose generic combination of 2 Nucleoside Analogs and the second tablet is the third antiretroviral. This study was a prospective observational study in a French hospital. During their follow-up, patients on stable single-tablet regimens were made aware of the possible cost-saving. They were questioned about their willingness and barriers accepting the substitution. Participants chose between the two regimens, either to remain on single-tablet regimens or switch to the de-simplified regimen. Six months later, a second survey was given to the patient who chose to de-simplify and HIV viral load was controlled. The study included 98 patients: 60 receiving emtricitabine/tenofovir disoproxil fumarate/rilpivirine (Eviplera.sup.®) and 38 on abacavir/lamivudine/dolutegravir (Triumeq.sup.®). Forty-five patients accepted the de-simplified treatment, 37 refused and 16 were undecided and followed the decision offered by their physician. The main reason for unwillingness to switch is the number of pills (77.3%). In multivariate model analysis, male patients (p = 0.001) who have taken antiretroviral therapy for over 20 years (p = 0.04) and who retrieve their treatment in their community hospital (p = 0.03) are more likely to accept the switch. Fifty-one patients accepted to replace their single-tablet regimens and six months later, the majority was satisfied; only four returned to single-tablet regimens because of suspected side effects. Half of the people living with HIV/AIDS in our cohort accepted to switch from brand single-tablet regimens to a two-tablet regimen containing generic drugs within a process that emphasizes health expenditure savings.
Journal Article
Electronic medical record alert increases HIV screening rates: the Foch hospital pilot POP-up project
by
Sveltlane, Dimi
,
Majerholc, Catherine
,
Mazaux, Laurence
in
Analysis
,
Care and treatment
,
Country of birth
2022
Background
Despite significant national human immunodeficiency virus (HIV) screening activity, there are persistent delays in screening, and many missed diagnostic opportunities. To facilitate targeted screening, an electronic medical record (EMR) alert reminder was applied in the Foch hospital. Screening rates after implementation were reported.
Methods
A prospective cohort analysis was performed in Foch Hospital between 24 April 2018 and 4 October 2019 among hospitalized patients born in high HIV prevalence countries and/or having social vulnerability criteria (universal health coverage). From the admissions software, when specific low health coverage was provided and/or high-prevalence country of birth was registered, an electronic alert (EMR alert) appeared on the ward where the patient was hospitalized. The EMR alert database was examined for HIV screening and activity responses from each service of the Hospital.
Results
Eight thousand one hundred eighty-one alerts were recovered during the period for 1448 patients. 27 services used the EMR alert. Most of the alerts were directly closed (74.4%), 14.5% of the alerts were closed due to doctors declaring that they did not have time to respond. 297 (3.6%) of the 8181 alerts resulted in a prescription of HIV serology corresponding for 20.5% of the patients.
Conclusion
EMR alert can help to increase the rate of HIV screening in hospital care practice. Through this EMR alert system, HIV screening can be implemented as a common practice like any other medical alternative. Future research should examine the factors influencing physicians’ attitudes to this alert system to improve the HIV screening rate.
Journal Article