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La communication interauriculaire (CIA) constitue la seconde cardiopathie congénitale la plus importante chez l'enfant, elle représente 6 à 8% des malformations congénitales cardiaques de l'enfant. Toutefois, de nombreuses questions demeurent ouvertes concernant cette pathologie. Ainsi notre objectif était de rapporter la prévalence hospitalière des CIA mais surtout d'en décrire les aspects cliniques, paracliniques et thérapeutiques. Pour y parvenir nous avons réalisé une étude rétrospective descriptive. Les données ont été recueillies grâce à un questionnaire puis saisies et analysées sur Sphinx (V5). La prévalence hospitalière était de 2 pour 1000. L'âge moyen était de 37mois et le sex-ratio de 0,75. Il n'y a eu aucun cas diagnostiqué en anténatal. Une consanguinité parentale était retrouvée dans 30% des cas. Les infections respiratoires étaient présentes dans 24% des cas. Une cardiomégalie était retrouvée dans 35 cas avec une hyper vascularisation pour 63%. L'échographie notait une prédominance du type ostium secundum; la CIA était large dans 63% des cas. La sténose pulmonaire représentait l'atteinte cardiaque associée la plus importante. L'HTAP était présente dans 63% des cas. Les diurétiques étaient très utilisés et seuls 7 enfants avaient bénéficié d'une cure chirurgicale. L'évolution était favorable chez 39 patients soit 79%. Le diagnostic précoce des CIA doit être amélioré ainsi que la prise en charge chirurgicale des formes avec retentissement du nourrisson.

La TVC est rare en général et particulièrement chez l'enfant. La survenue d'une HSA dans ce contexte est une situation très peu fréquente et seuls quelques cas sont rapportés dans la littérature. Sa symptomatologie est variable et souvent trompeuse. Non traitée ou en cas de traitement tardif l'issue peut être fatale ou conduire à des séquelles potentiellement graves. Nous rapportons l'observation d'un nourrisson de 22 mois reçu pour des convulsions avec coma stade II, syndrome d'hypertension intracrânienne et syndrome infectieux. Une septicémie à Pseudomonas spp a était retrouvée à la biologie et le scanner cérébral a permis de poser le diagnostic. Le traitement a été basé sur l'antibiothérapie mais surtout l'anticoagulation. Une nette amélioration clinique a été ainsi notée et le scanner cérébral de contrôle montrait une disparition de la thrombose avec images hémorragiques séquellaires droites. La TVC est une pathologie grave d'origine généralement infectieuse. Le traitement anticoagulant est aujourd'hui sujet à controverse notamment en cas d'hémorragie associée, mais l'expérience clinique serait en faveur de l'efficacité et de l'innocuité de ce traitement.

BackgroundThe COVID-19 pandemic has increased the number of patients in ICUs leading to a worldwide shortage of the intravenous sedative agents obligating physicians to find alternatives including inhaled sedation. Inhaled sedation in French ICU has been previously explored in 2019 (VOL'ICU study). This survey was designed to explore the use of inhaled sedation two years after our first survey and to evaluate how the COVID-19 pandemic has impacted the use of inhaled sedation.MethodsWe designed a national survey, contacting medical directors of French ICUs between June and October 2021. Over a 50-item questionnaire, the survey covered the characteristics of the ICU, data on inhaled sedation, and practical aspects of inhaled ICU sedation for both COVID-19 and non-COVID-19 patients. Answers were compared with the previous survey, VOL'ICU.ResultsAmong the 405 ICUs contacted, 25% of the questionnaires were recorded. Most ICU directors (87%) knew about the use of inhaled ICU sedation and 63% of them have an inhaled sedation's device in their unit. The COVID-19 pandemic increased the use of inhaled sedation in French ICUs. The main reasons said by the respondent were "need for additional sedative" (62%), "shortage of intravenous sedatives" (38%) and "involved in a clinical trial" (30%). The main reasons for not using inhaled ICU sedation were "device not available" (76%), "lack of familiarity" (60%) and "no training for the teams" (58%). More than 70% of respondents were overall satisfied with the use of inhaled sedation. Almost 80% of respondents stated that inhaled sedation was a seducing alternative to intravenous sedation for management of COVID-19 patients.ConclusionThe use of inhaled sedation in ICU has increased fastly in the last 2 years, and is frequently associated with a good satisfaction among the users. Even if the COVID-19 pandemic could have impacted the widespread use of inhaled sedation, it represents an alternative to intravenous sedation for more and more physicians.

Circadian rhythms have been described in numerous tissues of living organisms and are necessary for homeostasis. The understanding of their role in normal and pathological pregnancy is only just emerging. It has been established that clock genes are expressed in the placenta of animals and humans, but the rhythmicity of placenta immune cells is not known. Macrophages from healthy placenta of women at term were isolated and the expression of clock genes BMAL1, CLOCK, PER2, CRY2, and NR1D1 was assessed by qRT-PCR every 4 h over 24 h. Raw data were treated with cosinor analysis to evaluate the significance of the oscillations. Placental macrophages exhibited significant circadian expression of clock genes but one third of placental macrophages lost clock gene rhythmicity; the clock gene oscillations were restored by co-culture with trophoblasts. We wondered if melatonin, a key hormone regulating circadian rhythm, was involved in the oscillations of placental cells. We showed that macrophages and trophoblasts produced melatonin and expressed MT2 receptor. In women who developed preeclampsia during pregnancy, circadian oscillations of placental macrophages were lost and could not be rescued by coculture with trophoblasts from healthy women. Moreover, production and oscillations of melatonin were altered in preeclamptic macrophages. For the first time to our knowledge, this study shows circadian rhythms and melatonin production by placental macrophages. It also shows that preeclampsia is associated with a disruption of the circadian rhythm of placental cells. These results represent a new scientific breakthrough that may contribute to the prevention and treatment of obstetrical pathologies.

Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease in which the immune system attacks healthy tissues. While pharmaceutical therapies are an important part of disease management, behavioral interventions have been implemented to increase patients’ disease self-management skills, provide social support, and encourage patients to take a more active role in their care.Methods: Three interventions are considered in this study; peer-to-peer methodology, patient support group, and a patient navigator program that were implemented among largely African American women with SLE at the Medical University of South Carolina (MUSC). Outcomes of interest were patient activation and lupus self-efficacy. We used a Least Squares Means model to analyze change in total patient activation and lupus self-efficacy independently in each cohort. We adjusted for demographic variables of age, education, income, employment, and insurance.Results: In both unadjusted and adjusted models for patient activation, there were no statistically significant differences among the three intervention methodologies when comparing changes from baseline to post intervention. Differences in total coping score from baseline to post intervention in the patient navigator group (−101.23, p-value 0.04) and differences in scores comparing the patient navigator with the support group were statistically significant (116.96, p-value 0.038). However, only the difference in total coping from baseline to post intervention for the patient navigator program remained statistically significant (−98.78, p-value 0.04) in the adjusted model.Conclusion: Tailored interventions are a critical pathway toward improving disease self-management among SLE patients. Interventions should consider including patient navigation because this method was shown to be superior in improving self-efficacy (coping scores).

Objective The Care-coordination Approach to Learning Lupus Self-Management (CALLS) study was designed to improve SLE disease self-management. This study aims to assess the benefits of the intervention compared with existing lupus care.Methods Participants were randomly assigned to participate in 12-weekly phone sessions with the patient navigator that included structured educational content, care coordination and patient-centred support services, or a usual care control condition. Validated measures of health literacy, self-efficacy, patient activation and disease activity were collected. We used least squares means and linear mixed-effects regression models for each outcome variable to assess the changes in outcome, from baseline to postintervention and to estimate the difference in these changes between the intervention and control group.Results Thirty participants were enrolled and 14 were randomised to the treatment group. For perceived lupus self-efficacy, there was a significant increase in mean score for the intervention group, but not for the control group. With regard to disease activity, the experimental group experienced a slight decrease in mean flare score in the previous 3 months, whereas the control group experienced a slight increase, but this finding did not reach statistical significance. Trends were similar in self-reported global disease activity, but none of the findings were significant. Health literacy and patient activation measure scores remained largely unchanged throughout the study for the two groups.Conclusion These findings suggest that the CALLS intervention may work to improve aspects of SLE disease self-management. Future research will be needed to validate these findings long-term.Trial registration number NCT04400240.

Circadian rhythms are present in almost all living organisms, and their activity relies on molecular clocks. In prokaryotes, a functional molecular clock has been defined only in cyanobacteria. Here, we investigated the presence of circadian rhythms in non-cyanobacterial prokaryotes. The bioinformatic approach was used to identify a homologue of KaiC (circadian gene in cyanobacteria) in Escherichia coli. Then, strains of E. coli (wild type and mutants) were grown on blood agar, and sampling was made every 3 h for 24 h at constant conditions. Gene expression was determined by qRT-PCR, and the rhythmicity was analyzed using the Cosinor model. We identified RadA as a KaiC homologue in E. coli. Expression of radA showed a circadian rhythm persisting at least 3 days, with a peak in the morning. The circadian expression of other E. coli genes was also observed. Gene circadian oscillations were lost in radA mutants of E. coli. This study provides evidence of molecular clock gene expression in E. coli with a circadian rhythm. Such a finding paves the way for new perspectives in antibacterial treatment.

The rapid spread, severity, and lack of specific treatment for COVID-19 resulted in hasty drug repurposing. Conceptually, trials of antivirals were well-accepted, but twentieth century antimalarials sparked an impassioned global debate. Notwithstanding, antiviral and immunomodulatory effects of aminoquinolines have been investigated in vitro, in vivo and in clinical trials for more than 30 years. We review the mechanisms of action of (hydroxy)chloroquine on immune cells and networks and discuss promises and pitfalls in the fight against SARS-CoV-2, the agent of the COVID-19 outbreak.

The host defense against pathogens varies among individuals. Among the factors influencing host response, those associated with circadian disruptions are emerging. These latter depend on molecular clocks, which control the two partners of host defense: microbes and immune system. There is some evidence that infections are closely related to circadian rhythms in terms of susceptibility, clinical presentation and severity. In this review, we overview what is known about circadian rhythms in infectious diseases and update the knowledge about circadian rhythms in immune system, pathogens and vectors. This heuristic approach opens a new fascinating field of time-based personalized treatment of infected patients.

Abstract Background The long-term benefits of antiretroviral treatment (ART) are associated with metabolic complications, especially lipodystrophy, which has been well described among HIV-infected adults and children on ART in developed settings. Specifically, stavudine, and to a lesser extent zidovudine and protease inhibitors (PI), have been consistently implicated in the development of lipodystrophy. In 2006, following advice from the WHO, Senegal began phasing out stavudine from first-line ART. The objectives of this cross-sectional analysis are to assess and identify risk factors affecting the prevalence of lipodystrophy in Senegalese children and adolescents on long-term ART participating in a cohort study. Methods Lipodystrophy was clinically assessed in two- to 18-year-old children on ART for at least six months and with no concurrent severe acute malnutrition. Risk factors for lipodystrophy were identified using stepwise multivariable logistic regression. Explanatory variables included clinical and personal data, immunovirologic status, and therapeutic history. Results Overall, 254 children were assessed for lipodystrophy. The median age was 10.9 years (IQR: 8.1–14.2) and the median duration on ART was 54 months (32–84). Only 18% had been previously treated with stavudine, with a median treatment duration of 8 months (5–25). Ongoing treatment included 76% of children receiving zidovudine (median duration of 48 months (26–74)) and 27% receiving PI (lopinavir/ritonavir; median duration of 49 months (23–59)). Mild signs of lipodystrophy were observed in 33 children (13%): 28 with lipoatrophy, 4 with lipohypertrophy and one with combined type. Boys were more likely to present with lipoatrophy than girls (aOR: 4.3, 95% CI: 1.6–11.7). Children previously treated with stavudine for ≥1 year had a greater risk for lipoatrophy than those never exposed (3.8, 1.0–14.0), although the association was weak. There was no association between lipodystrophy and age or current or cumulative treatment with lopinavir/ritonavir or zidovudine. Conclusions We report low prevalence of mild lipodystrophy in children and adolescents on long-term ART receiving a stavudine-sparing regimen. These findings are reassuring for clinicians in low-income settings where zidovudine is massively prescribed and lopinavir/ritonavir is the only widely available PI. Trial registration ClinicalTrials.gov identifier: NCT01771562 (registration date: 01/18/2013).

The United States has a deficit of rheumatology specialists. This leads to an increased burden in accessing care for patients requiring specialized care. Given that most rheumatologists are located in urban centers at large hospitals, many lupus patients must travel long distances for routine appointments. The present work aims to determine whether travel burden is associated with increased levels of depression and anxiety among these patients. Data for this study were collected from baseline visits of patients participating in a lupus study at MUSC. A travel/economic burden survey was assessed as well as the 8-item Patient Health Questionnaire (PHQ-8) and the 7-item Generalized Anxiety Disorder (GAD-7) survey as measures of depression and anxiety, respectively. Linear regression models were used to assess the relationship between travel burden and depression and anxiety. Frequency of healthcare visits was significantly associated with increased depression (β = 1.3, p = 0.02). Significant relationships were identified between anxiety and requiring time off from work for healthcare appointments (β = 4, p = 0.02), and anxiety and perceived difficulty in traveling to primary care providers (β = 3.1, p = 0.04). Results from this study provide evidence that travel burden can have an effect on lupus patients’ anxiety and depression levels.

The intracellular bacterium Coxiella burnetii is responsible for Q fever, an infectious disease that increases the risk of abortion, preterm labor, and stillbirth in pregnant women. It has been shown that C. burnetii replicates in BeWo trophoblast cell line and inhibits the activation and maturation of decidual dendritic cells. Although tissue macrophages are known to be targeted by C. burnetii, no studies have investigated the interplay between placental macrophages and C. burnetii. Here, CD14+ macrophages from 46 full-term placentas were isolated by positive selection. They consisted of a mixed population of maternal and fetal origin as shown by genotype analysis. We showed that C. burnetii organisms infected placental macrophages after 4 h. When these infected macrophages were incubated for an additional 9-day culture, they completely eliminated organisms as shown by quantitative PCR. The ability of placental macrophages to form multinucleated giant cells was not affected by C. burnetii infection. The transcriptional immune response of placental macrophages to C. burnetii was investigated using quantitative real-time RT-PCR on 8 inflammatory and 10 immunoregulatory genes. C. burnetii clearly induced an inflammatory profile. Interestingly, the production by placental macrophages of interferon-γ, a cytokine known to be involved in efficient immune responses, was dramatically increased in response to C. burnetii. In addition, a clear correlation between interferon-γ production and C. burnetii elimination was found, suggesting that macrophages from full-term placentas eliminate C. burnetii under the control of an autocrine production of interferon-γ.

The circadian rhythm of the body temperature (CRBT) is a marker of the central biological clock that results from multiple complex biological processes. In mammals, including humans, the body temperature displays a strict circadian rhythm and has to be maintained within a narrow range to allow optimal physiological functions. There is nowadays growing evidence on the role of the temperature circadian rhythm on the expression of the molecular clock. The CRBT likely participates in the phase coordination of circadian timekeepers in peripheral tissues, thus guaranteeing the proper functioning of the immune system. The disruption of the CRBT, such as fever, has been repeatedly described in diseases and likely reflects a physiological process to activate the molecular clock and trigger the immune response. On the other hand, temperature circadian disruption has also been described as associated with disease severity and thus may mirror or contribute to immune dysfunction. The present review aims to characterize the potential implication of the temperature circadian rhythm on the immune response, from molecular pathways to diseases. The origin of CRBT and physiological changes in body temperature will be mentioned. We further review the immune biological effects of temperature rhythmicity in hosts, vectors, and pathogens. Finally, we discuss the relationship between circadian disruption of the body temperature and diseases and highlight the emerging evidence that CRBT monitoring would be an easy tool to predict outcomes and guide future studies in chronotherapy.

Retroviruses package their full-length, dimeric genomic RNA (gRNA) via specific interactions between the Gag polyprotein and a “Ψ” packaging signal located in the gRNA 5′-UTR. Rous sarcoma virus (RSV) gRNA has a contiguous, well-defined Ψ element, that directs the packaging of heterologous RNAs efficiently. The simplicity of RSV Ψ makes it an informative model to examine the mechanism of retroviral gRNA packaging, which is incompletely understood. Little is known about the structure of dimerization initiation sites or specific Gag interaction sites of RSV gRNA. Using selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE), we probed the secondary structure of the entire RSV 5′-leader RNA for the first time. We identified a putative bipartite dimerization initiation signal (DIS), and mutation of both sites was required to significantly reduce dimerization in vitro. These mutations failed to reduce viral replication, suggesting that in vitro dimerization results do not strictly correlate with in vivo infectivity, possibly due to additional RNA interactions that maintain the dimers in cells. UV crosslinking-coupled SHAPE (XL-SHAPE) was next used to determine Gag-induced RNA conformational changes, revealing G218 as a critical Gag contact site. Overall, our results suggest that disruption of either of the DIS sequences does not reduce virus replication and reveal specific sites of Gag–RNA interactions.

L'hypothyroïdie de l'enfant é été peu étudiée au Sénégal. Le but de cette étude était d'évaluer les aspects épidémiologiques, diagnostiques et évolutifs de l'hypothyroïdie congénitale. Il s'agissait d'une étude rétrospective descriptive et analytique portant sur tous les enfants suivis pour hypothyroïdie congénitale au Centre Hospitalier National d'Enfants Albert Royer sur la période de 2001 à 2014 (14 ans). A partir des dossiers des malades, nous avons recueilli et analysé les données sociodémographiques, cliniques et évolutives. Au total, 28 patients ont été inclus, soit une moyenne de 2 cas par an. L'âge moyen de découverte de l'hypothyroïdie était de 54,25 , 43 mois avec une prédominance féminine (Sex- ratio 0,47). Seuls 2 cas d'hypothyroïdie ont été diagnostiqués dans la période néonatale. La consanguinité était présente chez 68% des patients. Les signes cliniques étaient dominés par le retard des acquisitions psychomotrices (96%), l'hypothermie (46%), la dysmorphie cranio-faciale (43%) et le goitre (39%). Le retard statural était constant au-delà de 6 mois.

BackgroundSurrogate markers of protective immunity to malaria in humans are needed to rationalize malaria vaccine discovery and development. In an effort to identify such markers, and thereby provide a clue to the complex equation malaria vaccine development is facing, we investigated the relationship between protection acquired through exposure in the field with naturally occurring immune responses (i.e., induced by the parasite) to molecules that are considered as valuable vaccine candidates.Methods and findingsWe analyzed, under comparative conditions, the antibody responses of each of six isotypes to five leading malaria vaccine candidates in relation to protection acquired by exposure to natural challenges in 217 of the 247 inhabitants of the African village of Dielmo, Senegal (96 children and 121 older adolescents and adults). The status of susceptibility or resistance to malaria was determined by active case detection performed daily by medical doctors over 6 y from a unique follow-up study of this village. Of the 30 immune responses measured, only one, antibodies of the IgG3 isotype directed to merozoite surface protein 3 (MSP3), was strongly associated with clinical protection against malaria in all age groups, i.e., independently of age. This immunological parameter had a higher statistical significance than the sickle cell trait, the strongest factor of protection known against Plasmodium falciparum. A single determination of antibody was significantly associated with the clinical outcome over six consecutive years in children submitted to massive natural parasite challenges by mosquitoes (over three parasite inoculations per week). Finally, the target epitopes of these antibodies were found to be fully conserved.ConclusionsSince anti-MSP3 IgG3 antibodies can naturally develop along with protection against P. falciparum infection in young children, our results provide the encouraging indication that these antibodies should be possible to elicit by vaccination early in life. Since these antibodies have been found to achieve parasite killing under in vitro and in vivo conditions, and since they can be readily elicited by immunisation in naïve volunteers, our immunoepidemiological findings support the further development of MSP3-based vaccine formulations.