Search

Type 1 diabetes (T1D) is a prototypic T cell-mediated autoimmune disease. Because the islets of Langerhans are insulated from blood vessels by a double basement membrane and lack detectable lymphatic drainage, interactions between endocrine and circulating T cells are not permitted. Thus, we hypothesized that initiation and progression of anti-islet immunity required islet neolymphangiogenesis to allow T cell access to the islet. Combining microscopy and single cell approaches, the timing of this phenomenon in mice was situated between 5 and 8 wk of age when activated anti-insulin CD4 T cells became detectable in peripheral blood while peri-islet pathology developed. This peri-insulitis, dominated by CD4 T cells, respected the islet basement membrane and was limited on the outside by lymphatic endothelial cells that gave it the attributes of a tertiary lymphoid structure. As in most tissues, lymphangiogenesis seemed to be secondary to local segmental endothelial inflammation at the collecting postcapillary venule. In addition to classic markers of inflammation such as CD29, V-CAM, and NOS, MHC class II molecules were expressed by nonhematopoietic cells in the same location both in mouse and human islets. This CD45- MHC class II+ cell population was capable of spontaneously presenting islet Ags to CD4 T cells. Altogether, these observations favor an alternative model for the initiation of T1D, outside of the islet, in which a vascular-associated cell appears to be an important MHC class II-expressing and -presenting cell.

Abstract Relapse after immunosuppression (IS) treatment withdrawal is frequent in patients with Autoimmune Hepatitis (AIH), and non-invasive biomarkers predictive of this risk are lacking. We assessed the frequency of circulating T cell subsets as potential biomarkers of disease activity and predictor of the risk of relapse after IS withdrawal. Serum levels of the cytokine B-cell Activating Factor (BAFF) were also investigated. Blood samples from 58 patients with active AIH, 56 AIH patients in remission, and 31 patients with NASH were analyzed. The frequency of activated CD4+ T peripheral helper (TPH) cells (CD4+CD45RA-CXCR5-PD1+CD38+) and of activated CD8+ T cells (CD8+CD45RA-PD1+CD38+) were assessed by flow cytometry. BAFF levels were determined by ELISA. Activated TPH and CD8+ T cell frequencies were significantly increased in patients with active AIH compared to remission AIH or NASH (TPH: 0.88% of total CD3+ vs. 0.42% and 0.39% respectively, p 0.5% of total CD3+) and/or activated CD8+ T cells (> 0.18% total CD3+) had a higher risk of relapse (80% vs. 15% after 2 years, p = 0.0071). High BAFF serum concentration (> 213pg/ml) was also associated to a higher risk of relapse (57% vs. 11%, p = 0.0452). In conclusion, high frequency of activated TPH and of activated CD8+, as well as high levels of BAFF, before IS discontinuation, were significantly associated to a greater risk of relapse during the first two years. Thus, they represent promising biomarkers to provide personalized clinical follow-up for patients with AIH.

Summary: Background: The lack of sensitive field tests to diagnose blood stages and hypnozoite carriers prevents Testing and Treatment (TAT) strategies to achieve Plasmodium vivax elimination in low-transmission settings, but recent advances in Polymerase Chain Reaction (PCR) and serology position them as promising tools. This study describes a PCR-based TAT strategy (PCRTAT) implemented in Saint Georges (SGO), French Guiana, and explores alternative strategies (seroTAT and seroPCRTAT) to diagnose and treat P. vivax carriers. Methods: The PALUSTOP cohort study implemented in SGO (September 2017 to December 2018) screened participants for P. vivax using PCR tests and treated positive cases. Serology was also performed. Passive detection of P. vivax infection occurred during follow-up. Participants were categorised into overlapping treatment groups based on 2017 PCR and serological results. Strategies were described in terms of participants targeted or missed, primaquine contraindications (pregnancy, G6PD severe or intermediate deficiency), and sociodemographic characteristics. Findings: In 2017, 1567 inhabitants were included, aged 0–92 years. A total of 90 (6%) were P. vivax carriers and 390 seropositive (25%). PCRTAT missed 282 seropositive individuals while seroTAT would have missed 21 PCR-positive cases. Primaquine contraindications ranged from 12% to 17% across strategies. Interpretation: Serology and PCR are promising tools for targeted treatment strategies in P. vivax low-transmission settings, when field compatible sensitive tests will be available. Both seem necessary to capture blood stages and potential hypnozoite carriers, while avoiding mass treatment. However, high primaquine contraindications rates need consideration for successful elimination. Funding: Supported by European Funds for Regional Development, French Guiana Regional Health Agency, Pan American Health Organization, WHO, French Ministry for Research.

BackgroundUntreated hearing loss has an effect on cognition. It is hypothesized that the additional processing required to compensate for the sensory loss affects the cognitive resources available for other tasks and that this could be mitigated by a hearing device.MethodsThe impact on cognition of cochlear implants (CIs) was tested in 100 subjects, ≥60 years old, with bilateral moderately-severe to profound post linguistic deafness using hearing aids. Data was compared pre and 12 and 18 months after cochlear implantation for the speech spatial qualities questionnaire, Mini Mental State Examination (MMSE), Trail making test B (TMTB) and digit symbol coding (DSC) from the Wechsler Adult Intelligence Scale version IV and finally the timed up and go test (TUG). Subjects were divided into young old (60–64), middle old (65–75) and old old (75+) groups. Cognitive test scores and times were standardized according to available normative data.ResultsHearing significantly improved pre- to post-operatively across all age groups. There was no change post-implant in outcomes for TMTB, TUG or MMSE tests. Age-corrected values were within normal expectations for all age groups for the TUG and MMSE. However, DSC scores and TMTB times were worse than normal. There was a significant increase in DSC scores between baseline and 12-months for 60- to 64-year-olds (t[153] = 2.608, p = 0.027), which remained at 18 months (t[153] = 2.663, p = 0.023).DiscussionThe improved attention and processing speed in the youngest age group may be a consequence of reallocation of cognitive resources away from auditory processing due to greatly improved hearing. The oldest age group of participants had cognition scores closest to normal values, suggesting that only the most able older seniors tend to come forward for a CI. Severe to profoundly deaf individuals with hearing aids or cochlear implants were still poorer than age-equivalent normally hearing individuals with respect to cognitive flexibility, attention, working memory, processing speed and visuoperceptual functions. Due to a lack of data for the TUG, TMTB and DSC in the literature for hearing impaired individuals, the results reported here provide an important set of reference data for use in future research.

Abstract Background Plasmodium vivax relapses due to dormant liver hypnozoites can be prevented with primaquine. However, the dose must be adjusted in individuals with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. In French Guiana, assessment of G6PD activity is typically delayed until day (D)14 to avoid the risk if misclassification. This study assessed the kinetics of G6PD activity throughout P. vivax infection to inform the timing of treatment. Methods For this retrospective monocentric study, data on G6PD activity between D1 and D28 after treatment initiation with chloroquine or artemisinin-based combination therapy were collected for patients followed at Cayenne Hospital, French Guiana, between January 2018 and December 2020. Patients were divided into three groups based on the number of available G6PD activity assessments: (i) at least two measurements during the P. vivax malaria infection; (ii) two measurements: one during the current infection and one previously; (iii) only one measurement during the malaria infection. Results In total, 210 patients were included (80, 20 and 110 in groups 1, 2 and 3, respectively). Data from group 1 showed that G6PD activity remained stable in each patient over time (D1, D3, D7, D14, D21, D28). None of the patients with normal G6PD activity during the initial phase (D1–D3) of the malaria episode (n = 44) was categorized as G6PD-deficient at D14. Patients with G6PD activity

There is an urgent need for countries to transition their national food and land-use systems toward food and nutritional security, climate stability, and environmental integrity. How can countries satisfy their demands while jointly delivering the required transformative change to achieve global sustainability targets? Here, we present a collaborative approach developed with the FABLE—Food, Agriculture, Biodiversity, Land, and Energy—Consortium to reconcile both global and national elements for developing national food and land-use system pathways. This approach includes three key features: (1) global targets, (2) country-driven multi-objective pathways, and (3) multiple iterations of pathway refinement informed by both national and international impacts. This approach strengthens policy coherence and highlights where greater national and international ambition is needed to achieve global goals (e.g., the SDGs). We discuss how this could be used to support future climate and biodiversity negotiations and what further developments would be needed.

Background: Homeless people have a higher risk of COVID-19 infection, linked to several social, economic and environmental determinants, frequent comorbidities, obstacles to exercising their constitutional social and health rights, poor medical cover, and insufficient use of the healthcare system. Data on COVID-19 vaccine uptake and its main determinants are lacking for this underserved population. Objectives: To construct and test a conceptual framework to model structural social determinants of COVID-19 vaccine uptake among underserved homeless populations, and to test this model to identify the determinants of COVID-19 vaccine uptake on the homeless population living in two metropolitan areas in France. Methods: We implemented a multicenter cross-sectional survey from 15/11/2021 to 22/12/2021 in homeless adults in the city of Marseille and in the greater Paris area. Persons sheltered in migrant worker hostels or in emergency social shelters, members of the COVID HOMELESS cohort study in Marseille, and Travelers living in traditional housing were all eligible. A standardized face-to-face questionnaire was administered to the participants where they lived in various languages by trained interviewers. We used structural equation modeling to analyze the structural social determinants of COVID-19 vaccine uptake, the latter defined as receiving at least one dose. Results: The participation rate was 64 %, accounting for 3811 participants. There were three main factors associated with greater vaccine uptake: i) opportunity, which included having a personal general practitioner (β = 0.05, p

IntroductionGiven the high infection rate of sexually transmitted infections (STI) among migrant women sex workers (WSWs), it is necessary to understand how to improve prevention, information and care for this vulnerable population. Community health workers (CHWs), by linking community to health services, are positioned to improve health outcomes in migrant communities. This article aims to describe a pilot innovative intervention performed by CHWs to improve sexual health in migrant WSWs.MethodsThis one-year intervention study used a respondent-driven sampling (RDS) to recruit a representative cohort of migrant WSWs in Marseille, France. Four CHWs were recruited from different communities and participated in all stages of the research. They performed individual and group interventions of prevention, support in care and empowerment. Data on participant characteristics, type of intervention and adherence to the intervention were reported via questionnaires given to participants. Simultaneously, semi-structured interviews and informal interviews of migrant WSW, CHWs and care providers were carried out.ResultsA total of 132 migrant WSWs were included in the cohort. Very few of them knew about PrEP (12%) or already used HIV post-exposure treatment (9%). Migrant WSWs were often victims of rape or racism, 15 and 21%, respectively. In two-thirds of cases the level of health literacy was low. Participants suffered from a combination of vulnerability factors: difficulties with access to social rights, food or housing. Only 13% reported having benefited from medical follow-up or assistance by an NGO in the 3 months prior to the program. By 3 months, more than one third of the participants had been tested for HIV (35%) and 63% knew about PrEP. A total retention rate of 70% was reported in the cohort after 6 months.ConclusionCHWs enabled to improve care access for migrant WSWs by improving the collaboration between care and social actors at a local level. Through these “bring-back-to” interventions for this hard-to-reach population, CHWs enabled an optimization of the care pathway. Our results also highlight the importance of a population-based approach for individual and group support of empowerment interventions in order to strengthen their capacity for action.

Abstract Background Hearing loss impacts health-related quality of life and general well-being and was identified in a Lancet report as one of the largest potentially modifiable factors for the prevention of age-related dementia. There is a lack of robust data on how cochlear implant treatment in the elderly impacts quality of life. The primary objective was to measure the change in health utility following cochlear implantation in individuals aged ≥ 60 years. Methods This study uniquely prospectively recruited a large multinational sample of 100 older adults (mean age 71.7 (SD7.6) range 60–91 years) with severe to profound hearing loss. In a repeated-measures design, pre and post implant outcome measures were analysed using mixed-effect models. Health utility was assessed with the Health Utilities Index Mark III (HUI3). Subjects were divided into groups of 60–64, 65–74 and 75 + years. Results At 18 months post implant, the mean HUI3 score improved by 0.13 (95%CI: 0.07–0.18 p 0.20). At baseline 90% of participants had no or mild depression and there was no change in mean depression scores after implant. Categories of Auditory perception scale showed that all subjects achieved a level of speech sound discrimination without lip reading post implantation (level 4) and at least 50% could use the telephone with a known speaker. Conclusions Better hearing improved individuals’ quality of life, ability to communicate verbally and their ability to function independently. They felt less lonely and less handicapped by their hearing loss. Benefits were independent of age group. Cochlear implants should be considered as a routine treatment option for those over 60 years with bilateral severe to profound hearing loss. Trial Registration ClinicalTrials.gov ( http://www.clinicaltrials.gov/ ), 7 March 2017, NCT03072862.

Abundance estimation of wildlife populations is frequently derived from systematic survey data. Accuracy and precision of estimates, however, depend on the number of replicate surveys, and on adjustments made for animals unavailable to (availability bias), or available but undetected (perception bias) by observers. This study offers a comprehensive analysis of the relative influence of methodological, environmental and behavioral factors on availability bias estimates from photographic and visual aerial surveys of a small cetacean with a highly clumped distribution, the beluga (Delphinapterus leucas). It also estimates the effect of the number of surveys on accuracy and precision of abundance estimates, using 28 replicate visual surveys flown within a 16—29 day window depending on survey year. Availability bias was estimated using detailed dive data from 27 beluga from the St. Lawrence Estuary, Canada, and applied to systematic visual and photographic aerial surveys of this population, flown using various survey platforms. Dive and surface interval durations varied among individuals, and averaged (weighted) 176.6 s (weighted s.e. = 12.6 s) and 51.6 s (weighted s.e. = 4.5 s), respectively. Dive time and instantaneous availability, but not surface time, were affected by local turbidity, seafloor depth, whale behavior (i.e., whether beluga were likely in transit or not), and latent processes that were habitat-specific. Overall, adjustments of availability for these effects remained minor compared to effects from survey design (photographic or visual) and type of platform, and observer search patterns. For instance, mean availability varied from 0.33—0.38 among photographic surveys depending on sightings distribution across the study area, but exceeded 0.40 for all visual surveys. Availability also varied considerably depending on whether observers searched within 0-90° (0.42—0.60) or 170° (0.70—0.80). Simulation-based power analysis indicates a large benefit associated with conducting more than 1 or 2 survey reps, but a declining benefit of conducting > 5—10 survey reps. An increase in sample size from 2, to 5, and 10 reps decreased the CV from 30, to 19 and 13%, respectively, and increased the probability of the abundance estimate being within 15% of true abundance from 0.42, to 0.59 and 0.69 in species like beluga.

IntroductionCertain living conditions, such as homelessness, increase health risks in epidemic situations. We conducted a prospective observational cohort study to investigate the impact of the COVID-19 pandemic on morbidity and mortality in adult people who were homeless.MethodsThe study population comprised around 40% of the entire population experiencing homelessness in Marseille. They were enrolled at 48 different locations during the first pandemic wave (June to August 2020) and were followed up 3 and 6 months later. Rapid serological screening for SARS-CoV-2 was performed by community outreach teams at each follow-up, who also conducted interviews. Death registers and hospital administrative databases were consulted.ResultsA total of 1,332 participants [mean age 40.1 years [SD 14.2], women 339 (29.9%)] were enrolled in the cohort. Of these, 192 (14.4%) participants were found positive for COVID-19 and were propensity score matched (1:3) and compared with 553 non-COVID-19 cases. Living in emergency shelters was associated with COVID-19 infection. While 56.3% of the COVID-19-infected cohort reported no symptoms, 25.0% were hospitalized due to the severity of the disease. Presence of three or more pre-existing comorbidities was associated with all-cause hospitalization. Among COVID-19 cases, only older age was associated with COVID-19 hospitalization. Three deaths occurred in the cohort, two of which were among the COVID-19 cases.ConclusionThe study provides new evidence that the population experiencing homelessness faces higher risks of infection and hospitalization due to COVID-19 than the general population. Despite the efforts of public authorities, the health inequities experienced by people who are homeless remained major. More intensive and appropriate integrated care and earlier re-housing are needed.

Abstract Background A steady decline in the number of cases of malaria was observed in the 2000s in French Guiana. This enabled regional health policies to shift their public health goal from control to elimination. To include inhabitants in this strategy, the main objective of this study was to describe knowledge about malaria, and related attitudes and practices in persons living in the French Guiana border. Methods We conducted a survey in people over 15 years old living in the twelve neighbourhoods of Saint-Georges de l’Oyapock with the highest malaria incidence. It comprised a 147-item questionnaire which collected data on socio-demographic characteristics and included a Knowledge Attitude and Practices survey on malaria. Knowledge-related data were studied using exploratory statistical methods to derive summary variables. A binary variable assessing level of knowledge was proposed and then assessed using exploratory approaches. Results The mean age of the 844 participants was 37.2 years [15.8], the male/female sex ratio was 0.8. In terms of nationality, 485 (57.5%) participants were Brazilian and 352 (41.7%) French. One third (305, 36.1%) spoke Brazilian Portuguese as their native language, 295 (34.9%) the Amerindian language Palikur, 36 (4.3%) French. The symptoms of malaria and prevention means were poorly known by 213 (25.2%) and 378 (44.8%) respondents, respectively. A quarter (206, 24.4%) did not know that malaria can be fatal. Overall, 251 people (29.7%) had an overall poor level of knowledge about malaria. Being under 25 years old, living in a native Amerindian neighbourhood, having an Amerindian mother tongue language, having risk behaviours related to gold mining were significantly associated with a poor level of knowledge. Conclusions This study is the first to describe the poor level of knowledge about malaria in populations living in the malaria endemic border area along the Oyapock river in French Guiana. Results will allow to reinforce, to diversify and to culturally adapt prevention messages and health promotion to increase their effectiveness with a view to quickly reaching the goal of malaria elimination through empowerment.

Abstract Molecular detection methods have revealed higher sensitivity and specificity than conventional microscopy or rapid diagnostic tests for malaria diagnosis. In this study, we implemented, evaluated and validated according to the ISO 15,189 requirements, a multiplex real-time PCR assay to detect and identify the five human malaria parasites. DNA samples were extracted from whole blood or dried blood spots drawn from patients. Based on the External Quality Assessment (whole blood), this method shows 100% sensitivity and specificity. This PCR detected P. vivax up to 0.25 p/µl, P. falciparum and P. knowlesi up to 0.5 p/µl, P. ovale up to 1 p/µl and P. malariae up to 5 p/µl of blood. From blood spots (extraction from four punches), it detected P. vivax at 5 p/µl, P. falciparum, P. ovale and P. knowlesi at 20 p/µl and P. malariae at 125 p/µl. In conclusion, this quantitative PCR shows excellent performance, is easy to use and DNA saver. It is especially useful to actively screen large population groups and identify the five human malaria parasites in a context of low malaria transmission.

Abstract Cystic fibrosis related diabetes (CFRD) is observed in 20–50% of adults with cystic fibrosis (CF). Pancreas abnormalities on imaging, e.g. pancreas lipomatosis, are frequent in subjects with CF. We hypothesized that specific abnormalities may characterize patients with CFRD. We performed a retrospective study comparing the computed tomography (CT) of participants with CF with or without diabetes (“CFRD” and “CF control” groups). We classified the pancreas on imaging according to 3 categories: normal, partial lipomatosis and complete lipomatosis of the pancreas. We also assessed the presence or absence of pancreatic calcifications. Forty-one CFRD and 53 CF control participants were included. Only 2% of the patients with CFRD had a normal pancreas, as compared with 30% of the participants from the CF control group (p = 0.0016). Lipomatosis was more frequent in subjects with CFRD and was related to exocrine pancreatic insufficiency (EPI) and to severe CFTR mutations (classes I to III). Nine participants with diabetes (22%) presented with pancreatic calcifications, versus none of the control participants (p = 0.0003). In conclusion, pancreas imaging was almost always abnormal in subjects with CFRD, while it was normal in a third of the CF control subjects. Pancreatic calcifications were specific of subjects with CFRD.

To leverage agriculture's potential to better benefit both people and nature, policymakers need clear messages about which farming practices positively impact biodiversity and yields, and when trade-offs arise. Existing reviews analyse effects of different agricultural practices on either biodiversity or yield, without considering interactions. Here, we applied multinomial and quantile regression models to synthesize global evidence of synergies and trade-offs between biodiversity and yield, using 764 paired observations (from 43 studies across 18 countries) comparing diversified and simplified farming systems. Results show that farmland diversification led to win-win outcomes for biodiversity and yield in 23% of cases, while a win for biodiversity coupled with a loss in yield was the most likely outcome (28% of cases). Yield and biodiversity responses were negatively correlated, meaning that diversifying farming systems solely in pursuit of production goals is unlikely to lead to markedly better outcomes for biodiversity, or vice-versa. Yet certain situations made win-win significantly more likely, including when crop and animal production, or multiple diversification practices (e.g., intercropping and cover crops), were combined, when no agrochemicals were applied, when diversification occurred in temperate climates, and when diversification enhanced below-ground taxa. Win-win was also more likely than lose-lose when biodiversity was measured as richness or richness-evenness, but not abundance, suggesting that in certain contexts diversified farming can effectively enhance species diversity while increasing agricultural yields. Overall, crop commodity group and bioclimatic location were amongst the most important contextual factors influencing the likelihood of a synergy or trade-off between biodiversity and yield, and diversification that accounts for these is less likely to lead to unexpected outcomes. Our novel method and up-to-date review show that farmland diversification frequently leads to better outcomes for biodiversity and/or agricultural production when compared to monocultures and farmland stripped of natural vegetation, opening a pathway to more sustainable agricultural production.