Dissecting the respective roles of microbiota and host genetics in the susceptibility of Card9-/- mice to colitis.

BACKGROUND: The etiology of inflammatory bowel disease (IBD) is unclear but involves both genetics and environmental factors, including the gut microbiota. Indeed, exacerbated activation of the gastrointestinal immune system toward the gut microbiota occurs in genetically susceptible hosts and under the influence of the environment. For instance, a majority of IBD susceptibility loci lie within genes involved in immune responses, such as caspase recruitment domain member 9 (Card9). However, the relative impacts of genotype versus microbiota on colitis susceptibility in the context of CARD9 deficiency remain unknown. RESULTS: Card9 gene directly contributes to recovery from dextran sodium sulfate (DSS)-induced colitis by inducing the colonic expression of the cytokine IL-22 and the antimicrobial peptides Reg3ß and Reg3γ independently of the microbiota. On the other hand, Card9 is required for regulating the microbiota capacity to produce AhR ligands, which leads to the production of IL-22 in the colon, promoting recovery after colitis. In addition, cross-fostering experiments showed that 5 weeks after weaning, the microbiota transmitted from the nursing mother before weaning had a stronger impact on the tryptophan metabolism of the pups than the pups' own genotype. CONCLUSIONS: These results show the role of CARD9 and its effector IL-22 in mediating recovery from DSS-induced colitis in both microbiota-independent and microbiota-dependent manners. Card9 genotype modulates the microbiota metabolic capacity to produce AhR ligands, but this effect can be overridden by the implantation of a WT or "healthy" microbiota before weaning. It highlights the importance of the weaning reaction occurring between the immune system and microbiota for host metabolism and immune functions throughout life. A better understanding of the impact of genetics on microbiota metabolism is key to developing efficient therapeutic strategies for patients suffering from complex inflammatory disorders. Video Abstract.

Toxoplasma gondii, a plea for a thorough investigation of its oncogenic potential.

It is estimated that 30 % of the world's population harbours the parasite Toxoplasma gondii, particularly in the brain. Beyond its implication in potentially severe opportunistic or congenital infections, this persistence has long been considered as without consequence. However, certain data in animals and humans suggest that this carriage may be linked to various neuropsychiatric or neurodegenerative disorders. The hypothesis of a potential cerebral oncogenicity of the parasite is also emerging. In this personal view, we will present the epidemiological arguments in favour of an association between toxoplasmosis and cerebral malignancy, before considering the points that could underlie a potential causal link. More specifically, we will focus on the brain as the preferred location for T. gondii persistence and the propensity of this parasite to interfere with the apoptosis and cell cycle signalling pathways of their host cell.

Experimental dataset of the impact assessment of vegetable intercropping on agroeconomic performances, pests and beneficials, and soil resources.

The data presented in this article were collected in the field at an experimental station in southern France under a Mediterranean climate. Experiments were conducted under three plastic walk-in tunnels used as blocks with organic farming practices over two successive years in a completely randomized design. The aim was to compare the intercropping of sweet pepper with basil, onion, lettuce, parsley or French bean to a sole crop of sweet pepper used as a control. The dataset provides information on cultural practices with details on inputs and working times used to estimate economic costs. The data also describe the climatic conditions under tunnels as well as the dynamics of soil nitrate concentration and water tension over time through treatments. Yields, economic benefits and the rates of products with visual defects are presented. In addition, some variables applied exclusively to sweet pepper crops, namely nitrate concentration in petiole sap, growth parameters, abundance of aerial pests and beneficials, incidence of root necrosis, arbuscular mycorrhizal fungi colonization rates and diversity in roots. The field dataset is made publicly available to allow free and easy access for the scientific and professional community to enable analysis and reuse. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Serum tryptophan metabolites are associated with erosive hand osteoarthritis and pain: results from the DIGICOD cohort.

OBJECTIVE: To investigate host and gut-microbiota related Tryptophan metabolism in hand osteoarthritis (HOA). METHODS: The baseline serum concentration of 20 Tryptophan metabolites was measured in 416 HOA patients in a cross-sectional analysis of the DIGICOD cohort. Tryptophan metabolites levels, metabolite-ratios and metabolism pathway activation were compared between erosive (N = 141) and non-erosive HOA (N = 275) by multiple logistic regressions adjusted on age, BMI and sex. The association between Tryptophan metabolite levels and HOA symptoms was investigated by a Spearman's rank correlation analysis. RESULTS: Four serum Tryptophan metabolites, eight metabolite ratios and one metabolism pathway were associated with erosive HOA. Erosive HOA was negatively associated with Tryptophan (odds ratio (OR) = 0.41, 95% confidence interval [0.24-0.70]), indole-3-aldehyde (OR = 0.67 [0.51-0.90]) and 3-OH-anthranilic acid (OR = 1.32 [1.13-1.54]) and positively with 5-OH-Tryptophan levels (OR = 1.41 [1.13-1.77]). The pro-inflammatory kynurenine-indoleamine 2,3-dioxygenase pathway was upregulated in erosive HOA (OR = 1.60 [1.11-2.29]). Eleven metabolites were correlated with HOA symptoms and were mostly pain-related. Serotonin and N-acetyl serotonin levels were negatively correlated with number of tender joints. Indole-3-aldehyde level was negatively correlated and 3-OH-anthranilic acid, 3-OH-kynurenine and 5-OH-Tryptophan levels were positively correlated with number of patients-reported painful joints. Quinolinic acid and 3-OH-kynurenine levels correlated positively with AUSCAN pain. CONCLUSIONS: Tryptophan metabolites disturbance is associated with erosive HOA and pain and emphasize the role of low-grade inflammation and gut dysbiosis in HOA.

The devil is in the detail: reflections on the value and application of cognitive interviewing to strengthen quantitative surveys in global health.

Cognitive interviewing is a qualitative research method for improving the validity of quantitative surveys, which has been underused by academic researchers and monitoring and evaluation teams in global health. Draft survey questions are administered to participants drawn from the same population as the respondent group for the survey itself. The interviewer facilitates a detailed discussion with the participant to assess how the participant interpreted each question and how they formulated their response. Draft survey questions are revised and undergo additional rounds of cognitive interviewing until they achieve high comprehension and cognitive match between the research team's intent and the target population's interpretation. This methodology is particularly important in global health when surveys involve translation or are developed by researchers who differ from the population being surveyed in terms of socio-demographic characteristics, worldview, or other aspects of identity. Without cognitive interviewing, surveys risk measurement error by including questions that respondents find incomprehensible, that respondents are unable to accurately answer, or that respondents interpret in unintended ways. This methodological musing seeks to encourage a wider uptake of cognitive interviewing in global public health research, provide practical guidance on its application, and prompt discussion on its value and practice. To this end, we define cognitive interviewing, discuss how cognitive interviewing compares to other forms of survey tool development and validation, and present practical steps for its application. These steps cover defining the scope of cognitive interviews, selecting and training researchers to conduct cognitive interviews, sampling participants, collecting data, debriefing, analysing the emerging findings, and ultimately generating revised, validated survey questions. We close by presenting recommendations to ensure quality in cognitive interviewing.

Behavioral, Hormonal, Inflammatory, and Metabolic Effects Associated with FGF21-Pathway Activation in an ALS Mouse Model.

In amyotrophic lateral sclerosis (ALS), motor neuron degeneration occurs simultaneously with systemic metabolic dysfunction and neuro-inflammation. The fibroblast growth factor 21 (FGF21) plays an important role in the regulation of both phenomena and is a major hormone of energetic homeostasis. In this study, we aimed to determine the relevance of FGF21 pathway stimulation in a male mouse model of ALS (mutated SOD1-G93A mice) by using a pharmacological agonist of FGF21, R1Mab1. Mice (SOD1-WT and mutant SOD1-G93A) were treated with R1Mab1 or vehicle. Longitudinal data about clinical status (motor function, body weight) and biological parameters (including hormonal, immunological, and metabolomics profiles) were collected from the first symptoms to euthanasia at week 20. Multivariate models were performed to identify the main parameters associated with R1Mab1 treatment and to link them with clinical status, and metabolic pathways involving the discriminant metabolites were also determined. A beneficial clinical effect of R1Mab1 was revealed on slow rotarod (p = 0.032), despite a significant decrease in body weight of ALS mice (p < 0.001). We observed a decrease in serum TNF-α, MCP-1, and insulin levels (p = 0.0059, p = 0.003, and p = 0.01, respectively). At 16 weeks, metabolomics analyses revealed a clear discrimination (CV-ANOVA = 0.0086) according to the treatment and the most discriminant pathways, including sphingolipid metabolism, butanoate metabolism, pantothenate and CoA biosynthesis, and the metabolism of amino acids like tyrosine, arginine, proline, glycine, serine, alanine, aspartate, and glutamate. Mice treated with R1Mab1 had mildly higher performance on slow rotarod despite a decrease on body weight and could be linked with the anti-inflammatory effect of R1Mab1. These results indicate that FGF21 pathway is an interesting target in ALS, with a slight improvement in motor function combined with metabolic and anti-inflammatory effects.

The specific metabolome profiling of patients infected by SARS-COV-2 supports the key role of tryptophan-nicotinamide pathway and cytosine metabolism.

The biological mechanisms involved in SARS-CoV-2 infection are only partially understood. Thus we explored the plasma metabolome of patients infected with SARS-CoV-2 to search for diagnostic and/or prognostic biomarkers and to improve the knowledge of metabolic disturbance in this infection. We analyzed the plasma metabolome of 55 patients infected with SARS-CoV-2 and 45 controls by LC-HRMS at the time of viral diagnosis (D0). We first evaluated the ability to predict the diagnosis from the metabotype at D0 in an independent population. Next, we assessed the feasibility of predicting the disease evolution at the 7th and 15th day. Plasma metabolome allowed us to generate a discriminant multivariate model to predict the diagnosis of SARS-CoV-2 in an independent population (accuracy > 74%, sensitivity, specificity > 75%). We identified the role of the cytosine and tryptophan-nicotinamide pathways in this discrimination. However, metabolomic exploration modestly explained the disease evolution. Here, we present the first metabolomic study in SARS-CoV-2 patients which showed a high reliable prediction of early diagnosis. We have highlighted the role of the tryptophan-nicotinamide pathway clearly linked to inflammatory signals and microbiota, and the involvement of cytosine, previously described as a coordinator of cell metabolism in SARS-CoV-2. These findings could open new therapeutic perspectives as indirect targets.

[Artesunate and severe malaria in paediatrics]. / Artésunate et paludisme sévère en pédiatrie.

Malaria is a life-threatening infection which affects especially non-immune subjects including children under the age of 5. Imported malaria is a rare disease in Europe but, with the increasing number of travelers and people who are visiting friends or relatives, it is important not to neglect it. Severe malaria leads to many pediatric deaths in countries with limited resources. The treatment of choice is a parenteral antimalarial. For a long time, only quinine was used in that case. Based on strong studies conducted in Asia and Africa, WHO (World Health Organization) has recommended the use of artesunate as a first-line treatment for severe malaria in adults and children since 2010.The use of artesunate has shown a reduction in mortality rate in severe malaria. In Europe, there still are several barriers to the implementation of these recommendations, especially in terms of availability and cost. In pediatrics departments and adults, artesunate is the first-line treatment in severe malaria, although close monitoring is essential, especially at the hematological side, monitoring the development of delayed post-artesunate haemolytic anemia (PADH), a known side effect.

Le paludisme est une infection potentiellement mortelle qui touche particulièrement les sujets non immuns, dont les enfants de moins de 5 ans. Le paludisme d'importation est une pathologie rare en Europe mais, devant l'augmentation du nombre de voyageurs et des personnes en visite dans leur pays d'origine, il est important de ne pas le négliger. L'accès palustre, dans sa forme sévère, entraîne de nombreux décès pédiatriques dans les pays en voie de développement. Le traitement de choix est un anti-malarique par voie parentérale. Pendant longtemps, seule la quinine était utilisée pour cette indication. Sur base de solides études menées en Asie et en Afrique, l'OMS (Organisation Mondiale de la Santé) préconise, depuis 2010, l'utilisation de l'artésunate en première ligne de traitement du paludisme sévère chez l'adulte et chez l'enfant. L'utilisation de l'artésunate permet une réduction de la mortalité dans l'accès palustre sévère. En Europe, plusieurs barrières persistent face à l'application de ces recommandations, notamment en termes de disponibilité et de coût. En pédiatrie et en médecine adulte, l'artésunate est le traitement de choix dans le paludisme sévère même si un monitoring étroit est indispensable, notamment au niveau hématologique, surveillant l'apparition d'anémie hémolytique différée post-artésunate (PADH), effet secondaire désormais reconnu.

Gender dynamics in digital health: overcoming blind spots and biases to seize opportunities and responsibilities for transformative health systems.

Much remains to ensure that digital health affirms rather than retrenches inequality, including for gender. Drawing from literature and from the SEARCH projects in this supplement, this commentary highlights key gender dynamics in digital health, including blind spots and biases, as well as transformative opportunities and responsibilities. Women face structural and social barriers that inhibit their participation in digital health, but are also frequently positioned as beneficiaries without opportunities to shape such projects to better fit their needs. Furthermore, overlooking gender relations and focussing on women in isolation can reinforce, rather than address, women's exclusions in digital health, and worsen negative unanticipated consequences. While digital health provides opportunities to transform gender relations, gender is an intimate and deeply structural form of social inequality that rarely changes due to a single initiative or short-term project. Sustained support over time, across health system stakeholders and levels is required to ensure that transformative change with one set of actors is replicated and reinforced elsewhere in the health system. There is no one size prescriptive formula or checklist. Incremental learning and reflection is required to nurture ownership and respond to unanticipated reactions over time when transforming gender and its multiple intersections with inequality.

Methodological development and biological observations of cell free DNA with a simple direct fluorescent assay in colorectal cancer.

BACKGROUND: Cell free DNA (cfDNA) has shown promising utility as prognostic biomarker for patients with colorectal cancer (CRC), with an ongoing need to optimize and validate the laboratory methodology. Here, we report our optimization and validation of a direct fluorescent assay and display the potential utility in patients with colorectal cancer. METHODS: Plasma cfDNA was analyzed by a direct fluorescent assay (DFA) and compared to quantification by droplet digital PCR (ddPCR). For clinical validation, baseline blood samples were available for a total of 273 patients from six different Nordic trials, covering patients with locally advanced rectal cancer (n = 176, cohorts A + B), liver limited metastatic CRC (n = 75C + D) and wide spread metastatic CRC (n = 22 E + F). RESULTS: Validating the DFA analysis with ddPCR revealed a strong correlation with an R2 of 0.81. For the clinical cohorts, the levels of cfDNA were: 0.8 ng/uL (95%CI 0.75-0.83) (A + B), 0.93 ng/uL (95%CI 0.86-1.02) (C + D) and 1.2 ng/uL (95%CI 0.85-1.47) (E + F), respectively (p < 0.01). All cohorts of colorectal cancer had higher levels of cell free DNA than healthy individuals (n = 94) (p < 0.01). CONCLUSION: Analysis of cell free DNA by a direct fluorescent assay could be an attractive laboratory option for a rapid inexpensive quantification of cell free DNA.

[Retinal hemangioblastoma: Treatment strategy and long-term follow-up in a retrospective cohort]. / Hémangioblastomes rétiniens : stratégie thérapeutique et suivi à long terme dans une cohorte rétrospective.

INTRODUCTION: Retinal hemangioblastoma (RH) is a benign vascular tumor frequently associated with Von Hippel-Lindau disease (VHL). Tumor growth of RH may lead to deterioration of visual acuity, which can be difficult to treat. Early diagnosis may reduce complication rate and side effects of treatment. The present retrospective study evaluates the long-term follow-up and complications of RH treatment as a function of the therapeutic strategy used. MATERIALS AND METHODS: The study included patients with RH, followed at Croix Rousse university hospital, Lyon between 2010 and 2017. The following clinical features were recorded : age at diagnosis, presenting symptom, presence of VHL disease, treatments used, post-therapeutic complications and visual outcomes. RESULTS: Seven eyes of five patients were included in our study. Eighty percent of the patients had a mutation in the VHL gene. Four eyes (57%) were treated with laser photocoagulation and three eyes (43%) were treated with cryotherapy. The mean duration of follow-up was 35 months. One of the eyes treated using laser photocoagulation was complicated by an early epiretinal membrane with no visual consequence. Of the eyes treated by cryoapplication, one was complicated by a vitreous hemorrhage, and another by a rhegmatogenous retinal detachment, both of which resulted in a decrease in visual acuity. CONCLUSION: The long-term outcome for patients treated for RH was relatively good. Complications were strongly correlated with the initial size of the vascular tumor. Early diagnosis seems to improve visual outcomes. Ophthalmologic monitoring should be part of the systemic, multidisciplinary management.

Where technology does not go: specialised neonatal care in resource-poor and conflict-affected contexts.

Setting: Although neonatal mortality is gradually decreasing worldwide, 98% of neonatal deaths occur in low- and middle-income countries, where hospital care for sick and premature neonates is often unavailable. Médecins Sans Frontières Operational Centre Brussels (MSF-OCB) managed eight specialised neonatal care units (SNCUs) at district level in low-resource and conflict-affected settings in seven countries. Objective: To assess the performance of the MSF SNCU model across different settings in Africa and Southern Asia, and to describe the set-up of eight SNCUs, neonate characteristics and clinical outcomes among neonates from 2012 to 2015. Design: Multicentric descriptive study. Results: The MSF SNCU model was characterised by an absence of high-tech equipment and an emphasis on dedicated nursing and medical care. Focus was on the management of hypothermia, hypoglycaemia, feeding support and early identification/treatment of infection. Overall, 11 970 neonates were admitted, 41% of whom had low birthweight (<2500 g). The main diagnoses were low birthweight, asphyxia and neonatal infections. Overall mortality was 17%, with consistency across the sites. Chances of survival increased with higher birthweight. Conclusion: The standardised SNCU model was implemented across different contexts and showed in-patient outcomes within acceptable limits. Low-tech medical care for sick and premature neonates can and should be implemented at district hospital level in low-resource settings.

Contexte: La mortalité néonatale diminue progressivement dans le monde, mais 98% des décès néonataux surviennent encore dans les pays à revenu faible et moyen, où les soins hospitaliers pour les nouveaux-nés malades et prématurés sont souvent indisponibles. Médecins Sans Frontières Centre d'Opérations Bruxelles (MSF-OCB) a géré huit unités spécialisées de soins néonataux (SNCU) au niveau du district dans des contextes de faibles ressources et affectés par des conflits dans sept pays.Objectif: Evaluer la performance du modèle de MSF-SNCU dans différents contextes en Afrique et en Asie du Sud Est. Les objectifs ont été de décrire la mise en place des huit SNCU, les caractéristiques des nouveau-nés et les résultats cliniques de 2012 à 2015.Schema: Etude descriptive multicentrique.Résultats: Le modèle de MSF-SNCU a été caractérisé par l'absence de machines de haute technologie et l'accent mis sur des soins infirmiers dévoués et des soins médicaux. La prise en charge s'est concentrée sur la gestion de l'hypothermie, de l'hypoglycémie, du soutien à l'alimentation et de l'identification/du traitement précoces d'une infection. Dans l'ensemble, 11 970 nouveau-nés ont été admis, dont 41% ont eu un faible poids de naissance (<2500 g). Les principaux diagnostics ont été un faible poids de naissance, une hypoxie et des infections néonatales. La mortalité d'ensemble a été de 17%, similaire dans les différents sites. Les chances de survie ont augmenté parallèlement au poids de naissance.Conclusion: Le modèle standardisé de SNCU a été mis en œuvre dans différents contextes et les résultats pour les nouveau-nés hospitalisés se sont avérés être dans des limites acceptables. Des soins médicaux de basse technologie pour les nouveau-nés malades et prématurés peuvent et doivent être mis en œuvre au niveau des hôpitaux de district dans les contextes de faibles ressources.

Marco de referencia: La mortalidad neonatal ha disminuido de manera gradual en todo el mundo, pero el 98% de las muertes neonatales ocurre en los países de bajos y medianos ingresos, que no suelen contar con una atención hospitalaria de los neonatos prematuros. El centro operativo de Bruselas de Médecins Sans Frontières (MSF-OCB) administra ocho unidades de atención neonatal especializada (SNCU) en entornos de bajos recursos y afectados por conflictos, a nivel distrital en siete países.Objetivo: Evaluar el desempeño del modelo SNCU de MSF en diferentes entornos en África y el sureste asiático. Se describe la puesta en marcha de ocho unidades, las características de los neonatos y los desenlaces clínicos del 2012 al 2015.Método: Fue este un estudio descriptivo multicéntrico.Resultados: El modelo SNCU de MSF se caracterizó por la falta de dispositivos de alta tecnología y una prioridad atribuida a la prestación de atención médica y de enfermería por parte de profesionales dedicados. Se concedió un interés especial al manejo de la hipotermia, la hipoglucemia, el apoyo alimentario y la detección precoz y el tratamiento de las infecciones. Se ingresaron 11 970 neonatos, de los cuales el 41% consistió en lactantes con bajo peso al nacer (<2500 g). Los principales diagnósticos fueron bajo peso al nacer, asfixia perinatal e infecciones neonatales. En general, la mortalidad fue 17%, en proporción uniforme en todos los centros. Las probabilidades de supervivencia aumentaban con un mayor peso al nacer.Conclusión: El modelo normalizado SNCU se introdujo en diferentes contextos y ofreció a los pacientes ingresados desenlaces dentro de límites aceptables. La atención médica de los neonatos prematuros y enfermos en plataformas de baja tecnología es viable y se debería introducir en los hospitales de nivel distrital de los entornos con bajos recursos.

How do low-birthweight neonates fare 2 years after discharge from a low-technology neonatal care unit in a rural district hospital in Burundi?

OBJECTIVES: As neonatal care is being scaled up in economically poor settings, there is a need to know more on post-hospital discharge and longer-term outcomes. Of particular interest are mortality, prevalence of developmental impairments and malnutrition, all known to be worse in low-birthweight neonates (LBW, <2500 g). Getting a better handle on these parameters might justify and guide support interventions. Two years after hospital discharge, we thus assessed: mortality, developmental impairments and nutritional status of LBW children. METHODS: Household survey of LBW neonates discharged from a neonatal special care unit in Rural Burundi between January and December 2012. RESULTS: Of 146 LBW neonates, 23% could not be traced and 4% had died. Of the remaining 107 children (median age = 27 months), at least one developmental impairment was found in 27%, with 8% having at least five impairments. Main impairments included delays in motor development (17%) and in learning and speech (12%). Compared to LBW children (n = 100), very-low-birthweight (VLBW, <1500 g, n = 7) children had a significantly higher risk of impairments (intellectual - P = 0.001), needing constant supervision and creating a household burden (P = 0.009). Of all children (n-107), 18% were acutely malnourished, with a 3½ times higher risk in VLBWs (P = 0.02). CONCLUSIONS: Reassuringly, most children were thriving 2 years after discharge. However, malnutrition was prevalent and one in three manifested developmental impairments (particularly VLBWs) echoing the need for support programmes. A considerable proportion of children could not be traced, and this emphasises the need for follow-up systems post-discharge.

[Gonococcal ophthalmia neonatorum: Clinical illustration, prevention, and future prospects]. / Conjonctivite néonatale à Neisseria Gonorrhoeae : illustration clinique, prophylaxie et perspectives d'avenir.

A 6-day-old infant presented with a bilateral suppurative ocular discharge with a conjunctival erythema. Polymerase chain reaction was performed on the pus and showed the presence of Neisseria gonorrhoeae DNA. Therapy with intravenous cefotaxime was initiated and completed with local application of tobramycin. This infection was associated with a small unilateral corneal lesion, with rapid resolution. This case provides the opportunity to focus on newborn suppurative conjunctivitis and its treatment. The different prophylaxes available (silver nitrate, povidone-iodine, local antibiotics, etc.) and their respective advantages and disadvantages are reviewed. There is no clear consensus on the most effective solution. Additionally, universal prophylaxis is challenged in several countries, where it is no longer recommended.

The development and evaluation of a community-based clinical diagnosis tool and treatment regimen for postpartum sepsis in Bangladesh and Pakistan.

BACKGROUND: Postpartum sepsis accounts for most maternal deaths between three and seven days postpartum, when most mothers, even those who deliver in facilities, are at home. Case fatality rates for untreated women are very high. Newborns of ill women have substantially higher infection risk. METHODS/DESIGN: The objectives of this study are to: (1) create, field-test and validate a tool for community health workers to improve diagnostic accuracy of suspected puerperal sepsis; (2) measure incidence and identify associated risk factors and; (3) describe etiologic agents responsible and antibacterial susceptibility patterns. This prospective cohort study builds on the Aetiology of Neonatal Infection in South Asia study in three sites: Sylhet, Bangladesh and Karachi and Matiari, Pakistan. Formative research determined local knowledge of symptoms and signs of postpartum sepsis, and a systematic literature review was conducted to design a diagnostic tool for community health workers to use during ten postpartum home visits. Suspected postpartum sepsis cases were referred to study physicians for independent assessment, which permitted validation of the tool. Clinical specimens, including urine, blood, and endometrial material, were collected for etiologic assessment and antibiotic sensitivity. All women with puerperal sepsis were given appropriate antibiotics. DISCUSSION: This is the first large population-based study to expand community-based surveillance for diagnoses, referral and treatment of newborn sepsis to include maternal postpartum sepsis. Study activities will lead to development and validation of a diagnostic tool for use by community health workers in resource-poor countries. Understanding the epidemiology and microbiology of postpartum sepsis will inform prevention and treatment strategies and improve understanding of linkages between maternal and neonatal infections.

Aspergillus spp. invasive external otitis: favourable outcome with a medical approach.

Aspergillus spp. invasive external otitis (IEO) is a rare infection. We performed a seven-year, single-centre retrospective study from 2007 to 2014 including all patients with proven Aspergillus spp. IEO. Twelve patients were identified. All patients had a poorly controlled diabetes mellitus and one underwent solid organ transplant. The most frequently isolated species was Aspergillus flavus (n = 10) and voriconazole was the first-line therapy in all cases, with a median length of treatment of 338.5 days (158-804 days). None of the patients underwent extensive surgery. The clinical outcome was excellent. However, otological sequelae were reported, including hearing impairment (n = 7) and facial palsy (n = 3).

[Mid-dermal elastolysis after insertion of a pacemaker]. / Élastolyse du derme moyen après pose d'un stimulateur cardiaque.

BACKGROUND: Mid-dermal elastolysis (MDE) is a rare acquired disease of elastic tissue histologically characterized by focal loss of elastic fibres within the mid-dermis. While the mechanisms leading to MDE remain unknown, increased degradation of elastic fibres may be involved. Many factors potentially triggering such degradation have been suggested. PATIENTS AND METHODS: A 58-year-old man consulted for an asymptomatic reticulated eruption that began in the area of a pacemaker implanted six weeks earlier. The eruption consisted of erythematous polycyclic and coalescing macules with a wrinkled centre. Histopathology with orcein staining revealed focal loss of elastic fibres in the superficial reticular dermis only. Hypersensitivity reaction to any components of the pacemaker was ruled out by means of allergy exploration. Laboratory investigations including autoimmunological and haematological factors were unremarkable. A diagnosis was made of a reticular variant of MDE following insertion of a pacemaker. DISCUSSION: We report the second case of MDE following the insertion of a pacemaker, which could have triggered an inflammatory response directed specifically towards the elastic fibres.

Methylation profile of the promoters of Nanog and Oct4 in ICSI human embryos.

STUDY QUESTION: What is the methylation status of the Nanog and Oct4 promoters in human gametes and ICSI embryos and is abnormal reprogramming of their methylation associated with developmental failure of ICSI embryos? SUMMARY ANSWER: Developmental failure of human ICSI embryos is associated with high methylation of the Oct4 promoter. WHAT IS KNOWN ALREADY: Nanog and Oct4 genes play critical roles in the establishment and maintenance of pluripotency during normal early embryonic development, and both are negatively regulated through the methylation of their promoters. STUDY DESIGN, SIZE AND DURATION: We analysed the methylation profile of Nanog and Oct4 promoters in 5 control sperm from normally fertile men, 70 metaphase II oocytes, 21 4-cell control ICSI embryos, 7 control blastocysts and 45 ICSI embryos arrested at 2- to 8-cell stage following prolonged culture. PARTICIPANTS, MATERIALS, SETTING AND METHODS: Embryos and gametes were donated for research by patients from the Department of Reproductive Medicine at the Hôpital Femme Mère Enfant (Bron, France) and the Clinique du Tonkin (Villeurbanne, France) after giving their informed consent. MAIN RESULTS: For both promoters, high methylation was observed in sperm cells. Although, in general, the promoters were unmethylated in oocytes, the methylation of some alleles was observed, particularly in oocytes from women with known infertility. Both gene promoters were hypomethylated in control blastocyst ICM (inner cell mass) and in control 2-8-cells embryos obtained from 6 out of 8 couples. However, they appeared highly methylated in embryos obtained from the other two couples. In most arrested ICSI embryos, the Nanog promoter was unmethylated while the Oct4 promoter was highly methylated. High methylation of the Oct4 promoter was significantly more pronounced in embryos from couples where a male factor was the only known cause of infertility. When the embryos were heterozygous for a G/A single nucleotide polymorphism, both alleles could be methylated, each likely representing a paternally inherited or a maternally inherited copy. LIMITATIONS AND REASONS FOR CAUTION: The study was done on a limited number of oocytes and embryos and the gametes of the couples were not available. WIDER IMPLICATIONS OF THE FINDINGS: These results provide new insight regarding the roles of epigenetic abnormalities in early developmental failure in humans. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. There was no competing interest.