Seroprevalence of anti-SARS-CoV-2 IgG at the first epidemic peak in French Guiana, July 2020.

Funder: National Research AgencyFunder: Regional Health Agency of French GuianaFunder: Institut Pasteur Urgence COVID-19 fundraisingBACKGROUND: While Latin America has been heavily affected by the pandemic, only a few seroprevalence studies have been conducted there during the first epidemic wave in the first half of 2020. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional survey was performed between 15 July 2020 and 23 July 2020 among individuals who visited 4 medical laboratories or 5 health centers for routine screening or clinical management, with the exception of symptomatic suggestive cases of covid-19. Samples were screened for the presence of anti-SARS-CoV-2 IgG directed against domain S1 of the SARS-CoV-2 spike protein using the anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) from Euroimmun. CONCLUSIONS/SIGNIFICANCE: The overall seroprevalence was 15.4% [9.3%-24.4%] among 480 participants, ranging from 4.0% to 25.5% across the different municipalities. The seroprevalence did not differ according to gender (p = 0.19) or age (p = 0.51). Among SARS-CoV-2 positive individuals, we found that 24.6% [11.5%-45.2%] reported symptoms consistent with COVID-19. Our findings revealed high levels of infection across the territory but a low number of resulting deaths, which can be explained by French Guiana's young population structure

SNUPN deficiency causes a recessive muscular dystrophy due to RNA mis-splicing and ECM dysregulation

SNURPORTIN-1, encoded by SNUPN, plays a central role in the nuclear import of spliceosomal small nuclear ribonucleoproteins. However, its physiological function remains unexplored. In this study, we investigate 18 children from 15 unrelated families who present with atypical muscular dystrophy and neurological defects. Nine hypomorphic SNUPN biallelic variants, predominantly clustered in the last coding exon, are ascertained to segregate with the disease. We demonstrate that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts and CRISPR/Cas9-mediated mutant cell lines. Additionally, mutant nuclei exhibit defective spliceosomal maturation and breakdown of Cajal bodies. Transcriptome analyses reveal splicing and mRNA expression dysregulation, particularly in sarcolemmal components, causing disruption of cytoskeletal organization in mutant cells and patient muscle tissues. Our findings establish SNUPN deficiency as the genetic etiology of a previously unrecognized subtype of muscular dystrophy and provide robust evidence of the role of SPN1 for muscle homeostasis

Mise en évidence des réarrangements du gène MLL dans les leucémies aigües par PCR ancrée

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

High incidence of acute Q fever among incarcerated people in Cayenne, French Guiana

Q fever is a major public health problem in French Guiana. In recent years, a considerable number of cases has been reported in French Guiana’s penitentiary center. The main objective of this study was to describe the epidemiology of these cases. A retrospective study was conducted at the prison to identify cases of acute Q fever in people incarcerated between 2010 and 2021. During the study period, 16 patients were diagnosed with acute Q fever. The positivity rate varied between 13 and 57%. The annual incidence rate in 2019, 2020 and 2021 was 269 (95% CI: 0-640) 1,120 (95% CI: 290-1950) and 1,931 (95% CI: 60-3810) per 100,000 person-years, respectively. While several vertebrate species have already been shown to play an important role in the transmission of Coxiella burnetii, the full epidemiology picture in the tropics is far from clear, and the prison context, with its controlled environment, could help provide answer

High endemicity of Q fever in French Guiana: A cross sectional study (2007–2017)

International audienceQ fever (QF) is a zoonosis caused by Coxiella burnetii (Cb). French Guiana (FG) had a high incidence but no data have been published since 2006. The objective of this study was to update the incidence and epidemiological data on QF in FG. A retrospective study of all FG Q fever serodiagnosis between 2007 and 2017 was carried out. Among the 695 patients included, the M/F sex-ratio was 2.0 and the median age of 45.3 years (IQR 33.7–56.3). The annual QF incidence rate was 27.4 cases (95%CI: 7.1–47.7) per 100,000 inhabitants ranging from 5.2 in 2007 to 40.4 in 2010. Risk factors associated with Q fever compared to general population were male gender, being born in mainland France, an age between 30 to 59 years-old and a residence in Cayenne and surroundings. The incidence of QF in FG remains high and stable and the highest in the world

Mr-Proadm Elevation Upon Icu Admission Predicts the Outcome of Septic Patients and is Correlated with Upcoming Fluid Overload

IF 3.113International audienceBackground: Among septic patients admitted to the intensive care unit (ICU), early recognition of those with the highest risk of death is of paramount importance. We evaluated the prognostic value of Procalcitonin (PCT), mid regional-proadrenomedullin (MR-proADM), copeptine and CT-proendothelin 1 (CT-ProET 1) concentrations. Methods: This was a prospective cohort study, which included 173 septic patient admitted to one ICU. Blood samples for biomarker measure-ments were obtained upon admission and on day 5. The predictive value of each biomarker regarding the risk of death at day 28 was assessed. The fluid balance was evaluated from admission to day 5. Results: All cause ICU mortality was 36.4%. All the biomarkers except CT-ProET-1 were significantly more elevated in the non-survivors than in the survivors upon day 1. Thiswas especially true for MR-proADM(8.6 [5.9] vs. 4.4 [3.9] nmol/L; P<0.0001) and for the CT-proET-1/MR-proADM ratio (52.9 [22.4] vs. 31.3 [26.6] arbitrary units; P < 0.0001). The best AUROCC values on day 1 were obtained with MR-ProADM and the CT-proET-1/MR-proADM ratio as well (0.75 [0.67-0.85] and 0.82 [0.75-0.89]; 95% CI, respectively). An improved accuracy was achieved on day 5. Moreover, MR-ProADM baseline levels and fluid balance over the 5-day period following ICU admission were strongly correlated (Rho = 0.41; P < 0.001). Conclusions: In patients admitted to the ICU with sepsis, MR-ProADM on admission was the best predictor of short-term clinical outcome if compared with others. This could be related to its ability to predict fluid sequestration

Epidemiology of Infection by Pulmonary Non-Tuberculous Mycobacteria in French Guiana 2008-2018.

International audienceINTRODUCTION: Unlike diseases caused by Mycobacterium tuberculosis, M. leprae and M. ulcerans, the epidemiology of pulmonary non-tuberculous mycobacteria (PNTM) has not received due attention in French Guiana. The main objective of the current study was to define the incidence of these PNTM infections: NTM pulmonary diseases (NTM-PD) and casual PNTM isolation (responsible of latent infection or simple colonization). The secondary objectives were to determine species diversity and geographic distribution of these atypical mycobacteria. METHODS: A retrospective observational study (2008-2018) of French Guiana patients with at least one PNTM positive respiratory sample in culture was conducted. Patients were then classified into two groups: casual PNTM isolation or pulmonary disease (NTM-PD), according to clinical, radiological and microbiological criteria defined by the American Thoracic Society / Infectious Disease Society of America (ATS / IDSA) in 2007. RESULTS: 178 patients were included, out of which 147 had casual PNTM isolation and 31 had NTM-PD. Estimated annual incidence rate of respiratory isolates was 6.17 / 100,000 inhabitants per year while that of NTM-PD was 1.07 / 100,000 inhabitants per year. Among the 178 patients, M. avium complex (MAC) was the most frequently isolated pathogen (38%), followed by M. fortuitum then M. abscessus (19% and 6% of cases respectively), the latter two mycobacteria being mainly found in the coastal center region. Concerning NTM-PD, two species were mainly involved: MAC (81%) and M. abscessus (16%). DISCUSSION/CONCLUSION: This is the first study on the epidemiology of PNTM infections in French Guiana. PNTM's incidence looks similar to other contries and metropolitan France and NTM-PD is mostly due to MAC and M.abscessus. Although French Guiana is the French territory with the highest tuberculosis incidence, NTM should not be overlooked

A progeroid syndrome caused by a deep intronic variant in TAPT1 is revealed by RNA/SI‐NET sequencing

Abstract Exome sequencing has introduced a paradigm shift for the identification of germline variations responsible for Mendelian diseases. However, non‐coding regions, which make up 98% of the genome, cannot be captured. The lack of functional annotation for intronic and intergenic variants makes RNA‐seq a powerful companion diagnostic. Here, we illustrate this point by identifying six patients with a recessive Osteogenesis Imperfecta (OI) and neonatal progeria syndrome. By integrating homozygosity mapping and RNA‐seq, we delineated a deep intronic TAPT1 mutation (c.1237‐52 G>A) that segregated with the disease. Using SI‐NET‐seq, we document that TAPT1's nascent transcription was not affected in patients' fibroblasts, indicating instead that this variant leads to an alteration of pre‐mRNA processing. Predicted to serve as an alternative splicing branchpoint, this mutation enhances TAPT1 exon 12 skipping, creating a protein‐null allele. Additionally, our study reveals dysregulation of pathways involved in collagen and extracellular matrix biology in disease‐relevant cells. Overall, our work highlights the power of transcriptomic approaches in deciphering the repercussions of non‐coding variants, as well as in illuminating the molecular mechanisms of human diseases

Loss of PYCR2 Causes Neurodegeneration by Increasing Cerebral Glycine Levels via SHMT2

Patients lacking PYCR2, a mitochondrial enzyme that synthesizes proline, display postnatal degenerative microcephaly with hypomyelination. Here we report the crystal structure of the PYCR2 apo-enzyme and show that a novel germline p.Gly249Val mutation lies at the dimer interface and lowers its enzymatic activity. We find that knocking out Pycr2 in mice phenocopies the human disorder and depletes PYCR1 levels in neural lineages. In situ quantification of neurotransmitters in the brains of PYCR2 mutant mice and patients revealed a signature of encephalopathy driven by excessive cerebral glycine. Mechanistically, we demonstrate that loss of PYCR2 upregulates SHMT2, which is responsible for glycine synthesis. This hyperglycemia could be partially reversed by SHMT2 knockdown, which rescued the axonal beading and neurite lengths of cultured Pycr2 knockout neurons. Our findings identify the glycine metabolic pathway as a possible intervention point to alleviate the neurological symptoms of PYCR2-mutant patients. Escande-Beillard et al. establish a mouse model of PYCR2 inactivation that phenocopies human neurodegenerative disease (HLD10). Metabolomic and functional analyses in mutant mice and patients reveal that cerebral hyperglycinemia is a driver of the disease, which can be corrected by inhibiting SHMT2

Impact of a stay in the intensive care unit on the preparation of Advance Directives: Descriptive, exploratory, qualitative study.

IF 1.542International audienceBACKGROUND:Our objective was to assess, through a qualitative, exploratory study, the thought processes of patients regarding the formulation of Advance Directives (AD) after a stay in the ICU.METHODS:Study performed from May to July 2016 using telephone interviews performed by four senior ICU physicians. Inclusion criteria were: patients discharged from ICU to home >3 months previously. Semi-directive interviews with patients focused on 5 main points surrounding AD.RESULTS:In total, among 159 eligible patients, data from 94 (59%) were available for analysis.Among all those interviewed, 83.5% had never heard of "Advance Directives". Only 2% had executed AD before ICU admission, and 7% expressed a desire to prepare AD further to their ICU stay. Among the barriers to preparation of AD, lack of information was the main reason cited for not executing AD. Patients noted the following in their AD:withdrawal of life-support in case of vegetative/minimally conscious state or when there is no longer any hope, in case of uncontrollable pain, and if impossible to wean from mechanical ventilation.CONCLUSION:The ideal time to engage patients in these discussions is most likely well before an acute health event occurs, although this warrants further investigation both before and after ICU admissions