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Le concept « une seule santé » lie étroitement la santé humaine et la santé animale car de nombreuses maladies sont des zoonoses. Les exemples historiques témoignant d’une collaboration efficace entre la médecine vétérinaire et la médecine humaine sont nombreux dans la mise au point des premiers vaccins utilisés dans le monde (variole, rage, tétanos, diphtérie, tuberculose, etc.). Mais lorsqu’une maladie nouvelle apparaît chez l’animal, le risque d’une transmission possible à l’Homme est difficile à estimer. Dans ce dernier cas, la perte de confiance du consommateur face aux incertitudes scientifiques peut provoquer une crise sanitaire (exemples de l’encéphalopathie spongiforme bovine et de la peste aviaire H5N1). Mais la plus grave crise que nous connaissons depuis le début de l’année 2020 est celle de la pandémie de Covid-19 qui confirme que la modification des écosystèmes de certaines espèces sauvages comme la chauve-souris fer à cheval peut avoir des conséquences importantes pour la santé publique. Les animaux ayant été malades de la Covid-19 ont été contaminés par l’Homme mais on ne peut pas exclure actuellement le risque de réservoir animal pour le SARS-CoV-2 qui a circulé dans le monde entier.

Summary The multidisciplinary International Committee for the Advancement of Procedural Sedation presents the first fasting and aspiration prevention recommendations specific to procedural sedation, based on an extensive review of the literature. These were developed using Delphi methodology and assessment of the robustness of the available evidence. The literature evidence is clear that fasting, as currently practiced, often substantially exceeds recommended time thresholds and has known adverse consequences, for example, irritability, dehydration and hypoglycaemia. Fasting does not guarantee an empty stomach, and there is no observed association between aspiration and compliance with common fasting guidelines. The probability of clinically important aspiration during procedural sedation is negligible. In the post‐1984 literature there are no published reports of aspiration‐associated mortality in children, no reports of death in healthy adults (ASA physical status 1 or 2) and just nine reported deaths in adults of ASA physical status 3 or above. Current concerns about aspiration are out of proportion to the actual risk. Given the lower observed frequency of aspiration and mortality than during general anaesthesia, and the theoretical basis for assuming a lesser risk, fasting strategies in procedural sedation can reasonably be less restrictive. We present a consensus‐derived algorithm in which each patient is first risk‐stratified during their pre‐sedation assessment, using evidence‐based factors relating to patient characteristics, comorbidities, the nature of the procedure and the nature of the anticipated sedation technique. Graded fasting precautions for liquids and solids are then recommended for elective procedures based upon this categorisation of negligible, mild or moderate aspiration risk. This consensus statement can serve as a resource to practitioners and policymakers who perform and oversee procedural sedation in patients of all ages, worldwide.

Background Domestic pets can contract severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection; however, it is unknown whether the UK B.1.1.7 variant can more easily infect certain animal species or increase the possibility of human‐to‐animal transmission. Methods This is a descriptive case series reporting SARS‐CoV‐2 B.1.1.7 variant infections in a group of dogs and cats with suspected myocarditis. Results The study describes the infection of domestic cats and dogs by the B.1.1.7 variant. Two cats and one dog were positive to SARS‐CoV‐2 PCR on rectal swab, and two cats and one dog were found to have SARS‐CoV‐2 antibodies 2–6 weeks after they developed signs of cardiac disease. Many owners of these pets had developed respiratory symptoms 3–6 weeks before their pets became ill and had also tested positive for COVID‐19. Interestingly, all these pets were referred for acute onset of cardiac disease, including severe myocardial disorders of suspected inflammatory origin but without primary respiratory signs. Conclusions These findings demonstrate, for the first time, the ability for pets to be infected by the B.1.1.7 variant and question its possible pathogenicity in these animals.

Although Zika virus (ZIKV) circulates in sub-Saharan Africa, no case of ZIKV-associated microcephaly has thus far been reported. Here, we report evidence of a possible association between a 2007 outbreak of febrile illness and an increase in microcephaly and possibly ZIKV infection in Gabon.

An association between malaria and risk for death among patients with Ebola virus disease has suggested within-host interactions between Plasmodium falciparum parasites and Ebola virus. To determine whether such an interaction might also influence the probability of acquiring either infection, we used a large snapshot surveillance study from rural Gabon to test if past exposure to Ebola virus is associated with current infection with Plasmodium spp. during nonepidemic conditions. We found a strong positive association, on population and individual levels, between seropositivity for antibodies against Ebola virus and the presence of Plasmodium parasites in the blood. According to a multiple regression model accounting for other key variables, antibodies against Ebola virus emerged as the strongest individual-level risk factor for acquiring malaria. Our results suggest that within-host interactions between malaria parasites and Ebola virus may underlie epidemiologic associations.

Domestic pets can contract SARS-CoV-2 infection but, based on the limited information available to date, it is unknown whether the new British B.1.1.7 variant can more easily infect certain animal species or increase the possibility of human-to-animal transmission. In this study, we report the first cases of infection of domestic cats and dogs by the British B.1.1.7 variant of SARS-CoV-2 diagnosed at a specialist veterinary hospital in the South-East of England. Furthermore, we discovered that many owners and handlers of these pets had developed Covid-19 respiratory symptoms 3-6 weeks before their pets became ill and had also tested PCR positive for Covid-19. Interestingly, all these B.1.1.7 infected pets developed atypical clinical manifestations, including severe cardiac abnormalities secondary to myocarditis and a profound impairment of the general health status of the patient but without any primary respiratory signs. Together, our findings demonstrate for the first time the ability for companion animals to be infected by the B.1.1.7 variant of SARS-CoV-2 and raise questions regarding its pathogenicity in these animals. Moreover, given the enhanced infectivity and transmissibility of B.1.1.7 variant for humans, these findings also highlights more than ever the risk that companion animals may potentially play a significant role in SARS-CoV-2 outbreak dynamics than previously appreciated.

The increased research on bat coronaviruses after severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) allowed the very rapid identification of SARS-CoV-2. This is an excellent example of the importance of knowing viruses harbored by wildlife in general, and bats in particular, for global preparedness against emerging viral pathogens., Bats host many viruses pathogenic to humans, and increasing evidence suggests that rotavirus A (RVA) also belongs to this list. Rotaviruses cause diarrheal disease in many mammals and birds, and their segmented genomes allow them to reassort and increase their genetic diversity. Eighteen out of 2,142 bat fecal samples (0.8%) collected from Europe, Central America, and Africa were PCR-positive for RVA, and 11 of those were fully characterized using viral metagenomics. Upon contrasting their genomes with publicly available data, at least 7 distinct bat RVA genotype constellations (GCs) were identified, which included evidence of reassortments and 6 novel genotypes. Some of these constellations are spread across the world, whereas others appear to be geographically restricted. Our analyses also suggest that several unusual human and equine RVA strains might be of bat RVA origin, based on their phylogenetic clustering, despite various levels of nucleotide sequence identities between them. Although SA11 is one of the most widely used reference strains for RVA research and forms the backbone of a reverse genetics system, its origin remained enigmatic. Remarkably, the majority of the genotypes of SA11-like strains were shared with Gabonese bat RVAs, suggesting a potential common origin. Overall, our findings suggest an underexplored genetic diversity of RVAs in bats, which is likely only the tip of the iceberg. Increasing contact between humans and bat wildlife will further increase the zoonosis risk, which warrants closer attention to these viruses.

Context: Although cerebral perfusion (CP) is preserved across a wide range of mean arterial pressures (MAP) through cerebral-vascular autoregulation, the relationship between MAP and CP in refracto...

Despite the probable zoonotic origin of SARS-CoV-2, only limited research efforts have been made to understand the role of companion animals in SARS-CoV-2 epidemiology. According to recent serological prevalence studies, human-to-companion animal transmission is quite frequent, which led us to consider that the risk of SARS-CoV-2 transmission from animal to human, albeit negligible in the present context, may have been underestimated. In this study, we provide the results of a prospective survey that was conducted to evaluate the SARS-CoV-2 isolation rate by qRT-PCR in dogs and cats with different exposure risks and clinical statuses. From April 2020 to April 2021, we analyzed 367 samples and investigated the presence of SARS-CoV-2 RNA using qRT-PCR. Only four animals tested positive, all of them being cats. Three cats were asymptomatic and one presented a coryza-like syndrome. We describe in detail the infection in two cats and the associated clinical characteristics. Importantly, we obtained SARS-CoV-2 genomes from one infected animal and characterized them as Alpha variants. This represents the first identification of the SARS-CoV-2 Alpha variant in an infected animal in France.

International audience; Background: Cervical cancer is the fourth most common malignancy in women worldwide. However, screening with human papillomavirus (HPV) molecular tests holds promise for reducing cervical cancer incidence and mortality in low-and middle-income countries. The performance of the Abbott RealTime High-Risk HPV test (AbRT) was evaluated in 83 cervical smear specimens and compared with a conventional nested PCR coupled to high-throughput sequencing (HTS) to identify the amplicons.Results: The AbRT assay detected at least one HPV genotype in 44.57% of women regardless of the grade of cervical abnormalities. Except for one case, good concordance was observed for the genotypes detected with the AbRT assay in the high-risk HPV category determined with HTS of the amplicon generated by conventional nested PCR.Conclusions: The AbRT test is an easy and reliable molecular tool and was as sensitive as conventional nested PCR in cervical smear specimens for detection HPVs associated with high-grade lesions. Moreover, sequencing amplicons using an HTS approach effectively identified the genotype of the hrHPV identified with the AbRT test.

Nadolol is a β-adrenergic antagonist that has been shown to be efficacious in the treatment of infantile hemangioma. It has been suggested that this drug may have fewer side effects compared with the gold standard therapy, propranolol, because it does not exhibit membrane-stabilizing effects and has little ability to cross the blood-brain barrier. However, the pharmacokinetics and safety of nadolol in infants are not well understood, potentially making this therapy dangerous. β-adrenergic antagonist toxicity causes bradycardia, hypotension, hypoglycemia, and even death. We report a case of a 10-week-old girl who was started on nadolol for infantile hemangioma, died 7 weeks later, and was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. The infant had no bowel movements for 10 days before her death, which we hypothesize contributed to nadolol toxicity. Pharmacokinetics studies show a large fraction of oral nadolol either remains in the feces unchanged or is excreted into feces via the biliary system, allowing continued absorption over time in infants who stool infrequently. Propranolol may be a safer therapy overall. Not only does it have a shorter half-life, but propranolol is hepatically metabolized and renally eliminated, allowing for less drug accumulation in healthy infants with variable stooling patterns. We suggest that if nadolol is selected for therapy, pediatricians should instruct parents to monitor their infants’ bowel movements closely and encourage early intervention in the event of decreased stooling. This intervention may greatly improve the safety of nadolol in this vulnerable patient population.

INTRODUCTION: Calcium channel blocker (CCB) overdoses cause significant morbidity and mortality. Dihydropyridine CCBs cause peripheral vascular dilation and at high doses cardiac dysfunction. Amlodipine, a dihydropyridine, causes peripheral vasodilation from release of nitric oxide (NO) in addition to calcium channel blockade; NO scavenging is a potential treatment. Methylene blue (MB) inhibits NO directly and inhibits NO production. We compared the effects of MB versus norepinephrine (NE), with time to death as the primary outcome, in a porcine amlodipine toxicity model. METHODS: Animals were anesthetized and instrumented, and an amlodipine infusion was administered to mimic oral overdose. After 70 minutes, each group was resuscitated with normal saline. Animals in each group were then randomized to receive either MB or NE. Hemodynamic parameters, including mean arterial pressure and cardiac output, were recorded every 10 minutes. The primary outcome was survival time (Kaplan-Meier analysis and log-rank test). RESULTS: Interim analysis after 15 animals (7 MB, 8 NE) revealed that MB was clearly not superior to NE. Overall, 1 of 7 animals in the MB group survived to 300 minutes compared with 2 of 8 animals in the NE group. The median survival time was 100 minutes for the MB group and 177 minutes for the NE group. Survival time did not differ by group (log-rank test p = 0.29). CONCLUSION: In this porcine model of amlodipine toxicity, methylene blue did not improve survival time compared with norepinephrine. Whether methylene blue is beneficial in combatting distributive shock in amlodipine toxicity remains unclear and requires further study.

Although pain is one of the most prevalent and bothersome symptoms children with cancer experience, evidence-based guidance regarding assessment and management is lacking. With 44 international, multidisciplinary healthcare professionals and nine patient representatives, we aimed to develop a clinical practice guideline (following GRADE methodology), addressing assessment and pharmacological, psychological, and physical management of tumor-, treatment-, and procedure-related pain in children with cancer. In this paper, we present our thorough methodology for this development, including the challenges we faced and how we approached these. This lays the foundation for our clinical practice guideline, for which there is a high clinical demand.

INTRODUCTION: Dextromethorphan hydrobromide is widely available as an over-the-counter cough suppressant. A semi-synthetic opioid displaying N-methyl-d-aspartate receptor antagonism, it is commonly abused for recreational purposes. Spuriously elevated serum chloride concentrations are a well-described phenomenon in the setting of dextromethorphan hydrobromide toxicity, but evidence to suggest the development of tolerance is limited to case reports. CASE: A 32-year-old male known to chronically ingest dextromethorphan hydrobromide for recreational purposes presented to regional hospitals on 179 occasions over 110 months and was treated for dextromethorphan toxicity on 163/174 (93.7%) of these visits. He reported a subjective need to increase his dosing over time to achieve the same degree of intoxication. Measured serum chloride over this period (n = 217) ranged from 98 to 138 mEq/L (median 115 mEq/L, IQR 110–123 mEq/L). Measured concentrations over the 110-month period progressively rose, with a fitted plot of 111.15 + 0.00232x describing the rise in measured chloride. Though not formally assessed, anion gaps tended to become progressively more negative over the observed period. DISCUSSION: We report a patient with persistent dextromethorphan hydrobromide abuse at escalating doses whose mean serum chloride concentration increased, on average, by 0.00232 mEq/L every day over a 110-month period. This case demonstrates progressive spurious hyperchloremia secondary to bromide interference in hospital-based chloride assays, supporting the patient’s reported need to dose escalate to the same desired effect. Although this artefactual laboratory finding is a well-documented result of bromide ingestion, it may be useful in identifying patterns of dextromethorphan hydrobromide use that suggest tolerance.

Although central Africa is classified as having a high endemicity of hepatitis B virus (HBV) and hepatitis D virus (HDV) infection, there is paucity of prevalence studies. For the first time on a country-wide level in Central Africa, we show in Gabon an overall 7.4% prevalence of Hepatitis B surface antigen (HBsAg) and that more than 25% of the HBsAg-positive population are infected by HDV. Although HBV prevalence did not differ significantly between provinces, there is a north-south split in the distribution of HDV seroprevalence, with the highest rates (>66.0%) correlating with the presence of specific ethnic groups in the northeastern provinces. Genotyping revealed high genetic diversity of the HBV and HDV strains circulating in Gabon, including many restricted to this region of the globe. This work confirmed that high exposure to HBV and HDV infection reported in selected regions of Gabon holds true across the whole country.

International audience; For more than 95% of acute febrile jaundice cases identified through surveillance for yellow fever, a reemerging arthropod-borne viral disease, no etiological exploration is ever done. The aim of this study was to test for other arthropod-borne viruses that can induce the same symptoms in patients enrolled in the yellow fever surveillance in the Democratic Republic of the Congo (DRC). Of 652 patients included in the surveillance of yellow fever in DRC from January 2003 to January 2012, 453 patients that tested negative for yellow fever virus (YFV) immunoglobulin M (IgM) antibodies were selected for the study. Real-time polymerase chain reaction was performed for the detection of dengue, West Nile, Chikungunya, O'nyong-nyong, Rift Valley fever, Zika, and YFV. The average age of patients was 22.1 years. We reported 16 cases (3.5%; confidence interval [CI]: 0.8-5.2) of dengue (serotypes 1 and 2) and 2 cases (0.4%; CI: 0.0-1.0) of Chikungunya. Three patients were co-infected with the two serotypes of dengue virus. Three cases of dengue were found in early July 2010 from the city of Titule (Oriental province) during a laboratory-confirmed outbreak of yellow fever, suggesting simultaneous circulation of dengue and yellow fever viruses. This study showed that dengue and Chikungunya viruses are potential causes of acute febrile jaundice in the DRC and highlights the need to consider dengue and Chikungunya diagnosis in the integrated disease surveillance and response program in the DRC. A prospective study is necessary to establish the epidemiology of these diseases.

Non-malarial febrile illness outbreaks were documented in 2007 and 2010 in Gabon. After investigation, these outbreaks were attributed to the chikungunya and dengue viruses (CHIKV and DENV). However, for more than half of the samples analyzed, the causative agent was not identified. Given the geographical and ecological position of Gabon, where there is a great animal and microbial diversity, the circulation of other emerging viruses was suspected in these samples lacking aetiology. A total of 436 undiagnosed samples, collected between 2007 and 2013, and originating from 14 urban, suburban, and rural Gabonese locations were selected. These samples were used for viral isolation on newborn mice and VERO cells. In samples with signs of viral replication, cell supernatants and brain suspensions were used to extract nucleic acids and perform real-time RT-PCR targeting specific arboviruses, i.e., CHIKV, DENV, yellow fever, Rift Valley fever, and West Nile and Zika viruses. Virus isolation was conclusive for 43 samples either on newborn mice or by cell culture. Virus identification by RT-PCR led to the identification of CHIKV in 37 isolates. A total of 18 complete genomes and 19 partial sequences containing the E2 and E1 genes of CHIKV were sequenced using next-generation sequencing technology or the Sanger method. Phylogenetic analysis of the complete genomes showed that all the sequences belong to the East Central South Africa lineage. Furthermore, we identified 2 distinct clusters. The first cluster was made up of sequences from the western part of Gabon, whereas the second cluster was made up of sequences from the southern regions, reflecting the way CHIKV spread across the country following its initial introduction in 2007. Similar results were obtained when analyzing the CHIKV genes of the E2 and E1 structural proteins. Moreover, study of the mutations found in the E2 and E1 structural proteins revealed the presence of several mutations that facilitate the adaptation to the Aedes albopictus mosquito, such as E2 I211T and E1 A226V, in all the Gabonese CHIKV strains. Finally, sequencing of 6 additional viral isolates failed to lead to any conclusive identification.

International audience; Canine distemper (CD) is the most deadly disease in dogs with mortality rates reaching 50%. The pathological agent, the CD virus (CDV), generally causes a severe systemic disease, although the nervous form can coexist with the acute catarrhal form in the same individual. In this study, we describe an outbreak of 18 cases of CD that occurred in 2015 in a German Shepherd dog population in northwestern Gabon. In addition, we determined the sequence of the CDV genotype associated with this fatal distemper infection in Gabon and compared it with other published CDV sequences. The CDV was detected using RT-PCR on cDNA from RNA of harvested brains and other organs. The identification was confirmed by sequencing amplicons. Moreover, we obtained the whole genome sequence using high-throughput sequencing. Phylogenetic analysis revealed that Gabonese CDV strain clustered with European strains belonging to the Europe genotype. This study provided the first molecular detection of the CDV strain associated with this fatal distemper infection in Central Africa region.

Chronic renal failure leads to many metabolic disorders affecting reproductive function. For men, hypergonadotropic hypogonadism, hyperprolactinemia, spermatic alterations, decreased libido and erectile dysfunction are described. Kidney transplantation improves sperm parameters and hormonal function within 2 years. But sperm alterations may persist with the use of immunosuppressive drugs. In women, hypothalamic-pituitary-ovarian axis dysfunction due to chronic renal failure results in menstrual irregularities, anovulation and infertility. After kidney transplantation, regular menstruations usually start 1 to 12 months after transplantation. Fertility can be restored but luteal insufficiency can persist. Moreover, 4 to 20% of women with renal transplantation suffer from premature ovarian failure syndrome. In some cases, assisted reproductive technologies can be required and imply risks of ovarian hyperstimulation syndrome and must be performed with caution. Pregnancy risks for mother, fetus and transplant are added to assisted reproductive technologies ones. Only 7 authors have described assisted reproductive technologies for patients with kidney transplantation. No cases of haemodialysis patients have been described yet. So, assisted reproductive technologies management requires a multidisciplinary approach with obstetrics, nephrology and reproductive medicine teams' agreement.

Rift Valley fever (RVF) is a zoonotic disease, which caused several epidemics in humans in many countries of Africa. Using an inhibition enzyme-linked immunosorbent assay (ELISA), real-time reverse transcription PCR, and nested one-step reverse transcription PCR, we conducted a cross-sectional study in populations of sheep and goats from the Mongo County in 2014 to determine the circulation of the Rift Valley fever virus (RVFV) in small ruminants from this area. From a total of 201 small ruminants (95 sheep and 106 goats), the overall IgG seroprevalence against the RVFV was 6.47% (13/201). No RVFV RNA was detected in the animal plasmas. Logistic regression analysis showed that age, species, sex, and locality were not the significant risk factors. The findings of this study highlight the risk of RVF for domestic ruminants bred in this region and for the human rural population living in contact with these animals and they emphasize the need to develop adequate control measures to limit this threat.

Sickle Cell Disease (SCD) is an important cause of death in young children in Africa, which the World Health Organization has declared a public health priority. Although SCD has been studied at the continental scale and at the local scale, a picture of its distribution at the scale of an African country has never been given. The aim of this study is to provide such a picture for the Republic of Gabon, a country where precisely the epidemiology of SCD has been poorly investigated. To this effect, 4250 blood samples from persons older than 15 were collected between June 2005 and September 2008 in 210 randomly selected villages from the nine administrative provinces of Gabon. Two methods were used to screen Sickle Cell Trait (SCT) carriers: isoelectric focusing (IEF) and high-performance liquid chromatography (HPLC). SCT prevalence in Gabon was 21.1% (895/4249). SCT prevalence was significantly larger for the Bantu population (21.7%, n = 860/3959) than for the Pygmy population (12.1%, n = 35/290), (p = 0.00013). In addition, the presence of Plasmodium sp. was assessed via thick blood examination. Age was positively associated with SCT prevalence (odds-ratio for an increase of 10 years in age = 1.063, p = 0.020). Sex was not associated with SCT prevalence. The study reveals the absence of homozygous sickle-cell patients, and marked differences in SCT prevalence between the Gabonese provinces, and also between population groups (Bantu vs Pygmy). These findings could be used by the public health authorities to allocate medical resources and target prevention campaigns.

Providing effective sedation and analgesia in infants and children admitted on a Pediatric Intensive Care Unit (PICU) is a cornerstone of daily patient care and probably one of the most challenging tasks facing PICU professionals. The wide range in age, weight and body composition, underlying medical and neurological diseases, the usually high sensory stimulatory environment, the repetitive physical stimuli related to medical therapy (e.g., physical examination, invasive procedures, and interventions) and—most importantly—the scarcity of high quality evidence applicable for daily practice may all contribute to this difficulty. A holistic comfort directed policy, including both pharmacological interventions as well as non-pharmacological strategies is promoted. For assessing comfort and/or pain several instruments are available. Particular attention should be paid to certain challenging clinical problems related to sedation, i.e. the management of refractory agitation, drug withdrawal and delirium.

Examination and comparison of the current DSM-IV-TR and the proposed revisions for the forthcoming DSM-5, with regard to neuropsychiatric aspects of critical illness, identified five important issues. These remain to be addressed in order to improve the care of critically ill patients. These are 1) sickness behavior, as part of the organic reaction types of the brain; 2) delirium in children and the "Differential Diagnosis of Mental Disorders Due to a General Medical Condition" in children; 3) catatonia; 4) regressive disorders in childhood in relation to somatic disorders (e.g., anti-NMDAR encephalitis); 5) age-related diagnostic criteria in relation to neuro-psychiatric disorders.

Background Extracorporeal photopheresis (ECP) is an established treatment for graft-versus-host disease (GVHD). Various haematocrit thresholds have been used to trigger red blood cells transfusion prior to ECP. Moderate-to-severe GVHD is frequently complicated by anaemia; the safety and collection efficiency with a lower haematocrit for ECP is unknown. Methods We prospectively enrolled 26 consecutive adult GVHD patients with haematocrits between 25% and 28·9% who received ECP on the CELLEX system. Preprocedural transfusion was withheld. We monitored the adverse events and transfusions avoided. A complete blood cell count with differential was performed on preprocedural peripheral blood and buffy coat collected. Lymphocyte fold enrichment (LFE) was compared between this cohort and two historical control groups with haematocrits of 29% or higher. Results Red Blood Cells transfusion was avoided in the lower-haematocrit cohort without adverse events. The median LFE was 4·5 (95%CI, 3·1–5·7) in the lower-haematocrit cohort and 5·2 (95%CI, 4·1–6·5) in the higher-haematocrit CELLEX-treated control group. The median difference was 0·7 (95%CI, −0·3 to 2·0, P = 0·14). It could not be established that the lower-haematocrit cohort was non-inferior to the higher-haematocrit control group with a prespecified non-inferiority margin of 1·3. However, LFE was significantly higher in the lower-haematocrit cohort than the higher-haematocrit UVAR XTS-treated control group (P < 0·01). Conclusion Buffy coat can be collected for ECP using CELLEX in GVHD patients with a haematocrit of 25% or higher, with a collection efficiency superior to that in patients with higher haematocrits but treated using UVAR XTS. No increase in adverse events was observed at these lower haematocrits.

Crimean Congo hemorrhagic fever virus (CCHFV) is a highly virulent tick-borne pathogen that causes hemorrhagic fever in humans. The geographic range of human CCHF cases largely reflects the presence of ticks. However, highly similar CCHFV lineages occur in geographically distant regions. Tick-infested migratory birds have been suggested, but not confirmed, to contribute to the dispersal. Bats have recently been shown to carry nairoviruses distinct from CCHFV. In order to assess the presence of CCHFV in a wide range of bat species over a wide geographic range, we analyzed 1,135 sera from 16 different bat species collected in Congo, Gabon, Ghana, Germany, and Panama. Using a CCHFV glycoprotein-based indirect immunofluorescence test (IIFT), we identified reactive antibodies in 10.0% (114/1,135) of tested bats, pertaining to 12/16 tested species. Depending on the species, 3.6%–42.9% of cave-dwelling bats and 0.6%–7.1% of foliage-living bats were seropositive (two-tailed t-test, p = 0.0447 cave versus foliage). 11/30 IIFT-reactive sera from 10 different African bat species had neutralizing activity in a virus-like particle assay. Neutralization of full CCHFV was confirmed in 5 of 7 sera. Widespread infection of cave-dwelling bats may indicate a role for bats in the life cycle and geographic dispersal of CCHFV.

Purpose of review Painful and/or stressful medical procedures mean a substantial burden for sick children. There is good evidence that procedural comfort can be optimized by a comprehensive comfort-directed policy containing the triad of non-pharmacological strategies (NPS) in all cases, timely or preventive procedural analgesia if pain is an issue, and procedural sedation. Recent findings Based both on well-established theoretical frameworks as well as an increasing body of scientific evidence NPS need to be regarded an inextricable part of procedural comfort care. Summary Procedural comfort care must always start with a child-friendly, nonthreatening environment in which well-being, confidence, and self-efficacy are optimized and maintained. This requires a reconsideration of the medical spaces where we provide care, reduction of sensory stimulation, normalized professional behavior, optimal logistics, and coordination and comfort-directed and age-Appropriate verbal and nonverbal expression by professionals. Next, age-Appropriate distraction techniques and/or hypnosis should be readily available. NPS are useful for all types of medical and dental procedures and should always precede and accompany procedural sedation. NPS should be embedded into a family-centered, care-directed policy as it has been shown that family-centered care can lead to safer, more personalized, and effective care, improved healthcare experiences and patient outcomes, and more responsive organizations.

International audience; Recent studies have revealed a large diversity of Plasmodium spp. among African great apes. Some of these species are related to Plasmodium falciparum, the most virulent agent of human malaria (subgenus Laverania), and others to Plasmodium ovale, Plasmodium malariae and Plasmodium vivax (subgenus Plasmodium), three other human malaria agents. Laverania parasites exhibit strict host specificity in their natural environment. Plasmodium reichenowi, Plasmodium billcollinsi, Plasmodium billbrayi and Plasmodium gaboni infect only chimpanzees, while Plasmodium praefalciparum, Plasmodium blacklocki and Plasmodium adleri are restricted to gorillas and Plasmodium falciparum is pandemic in humans. This host specificity may be due to genetic and/or environmental factors. Infrastructures hosting captive primates, such as sanctuaries and health centres, usually concentrate different primate species, thus favouring pathogen exchanges. Using molecular tools, we analysed blood samples from captive non-human primates living in Gabon to evaluate the risk of Plasmodium spp. transfers between host species. We also included blood samples from workers taking care of primates to assess whether primate-human parasite transfers occurred. We detected four transfers of Plasmodium from gorillas towards chimpanzees, one from chimpanzees to gorillas, three from humans towards chimpanzees and one from humans to mandrills. No simian Plasmodium was found in the blood samples from humans working with primates. These findings demonstrate that the genetic barrier that determines the apparent host specificity of Laverania is not completely impermeable and that parasite exchanges between gorillas and chimpanzees are possible in confined environments.

Hepatitis E virus (HEV) is one of the most common causes of acute hepatitis in tropical and temperate climates. Tropical genotypes 1 and 2 are associated with food-borne and waterborne transmission. Zoonotic reservoirs (mainly pigs, wild boar, and deer) are considered for genotypes 3 and 4, which exist in temperate climates. In view of the association of several zoonotic viruses with bats, we analyzed 3,869 bat specimens from 85 different species and from five continents for hepevirus RNA. HEVs were detected in African, Central American, and European bats, forming a novel phylogenetic clade in the family Hepeviridae . Bat hepeviruses were highly diversified and comparable to human HEV in sequence variation. No evidence for the transmission of bat hepeviruses to humans was found in over 90,000 human blood donations and individual patient sera. Full-genome analysis of one representative virus confirmed formal classification within the family Hepeviridae . Sequence- and distance-based taxonomic evaluations suggested that bat hepeviruses constitute a distinct genus within the family Hepeviridae and that at least three other genera comprising human, rodent, and avian hepeviruses can be designated. This may imply that hepeviruses invaded mammalian hosts nonrecently and underwent speciation according to their host restrictions. Human HEV-related viruses in farmed and peridomestic animals might represent secondary acquisitions of human viruses, rather than animal precursors causally involved in the evolution of human HEV.

Introduction: Weight loss amongst women with polycystic ovary syndrome (PCOS) is crucial to reduce the risk of endocrine, reproductive and metabolic complications including hirsutism, menstrual disturbances and cardiovascular disease. With approximately 50% of women with PCOS being overweight or obese, effective dietary management of weight in PCOS is essential. However, there is inconsistent evidence as to whether specifically modified diets (e.g. reduced carbohydrate diets) are more effective at achieving weight loss amongst women with PCOS than are conventional healthy hypocaloric diets. Material and Methods: A systematic review and meta-analysis of randomized controlled trials that had compared weight and BMI between women with PCOS who had undergone either a specifically modified diet or a conventional healthy hypocaloric diet were performed. Six electronic databases were searched, a manual search of the reference lists of the included studies was carried out and authors were contacted for additional information. Nine studies with a total of 395 participants (all with a body mass index [BMI] ≥30) were included in the meta-analysis. The effect size used was the mean difference in post-intervention weight and BMI between participants who had undergone a specifically modified diet and participants who had undergone a conventional healthy hypocaloric diet. Results: There were no differences between groups in post-intervention weight (mean difference 1.26, 95% confidence interval (CI) -0.92 to 3.43, p = .26; heterogeneity I2 = 50%, p = .04) or BMI (mean difference 0.15, 95% CI -0.93 to 1.23, p = 0.79; heterogeneity I2 = 44%, p = 0.10). Subgroup analyses according to the presence of a dietary run-in period (a period at the start of the study during which all participants are placed on an identical diet in order to equalize them on variables influenced by diet), intervention duration and type of diet and a sensitivity analysis according to study quality were not significant. Conclusions: Whilst the results should be interpreted in light of the moderate heterogeneity observed, they suggest that specifically modified diets offer no added benefit for weight loss in women with PCOS over conventional healthy hypocaloric diets. The findings of this meta-analysis may promote the unification of guidelines for the dietary management of PCOS and allow clinicians to be confident in prescribing conventional healthy hypocaloric diets for weight loss amongst their PCOS patients.

Chikungunya virus (CHIKV), an alphavirus of the Togaviridae family, is a small enveloped virus enclosing a single-stranded positive-sense RNA genome of approximately 12kb [1]. First isolated in 1953, CHIKV has since caused numerous outbreaks in Africa and Southeast Asia [1, 2]. In the last few years, CHIKV has spread to new regions of the world, including Indian Ocean islands [3–8], Central Africa [9–11] and even Europe [12]. A CHIKV outbreak in La Reunion island counted 266,000 clinical cases in 2005–2006 [3, 4], and at least 1.3 million cases were estimated in India in 2006–2007 [5–7]. Increased human mobility, spread of mosquito larvae through the international trade of used tires, and increased insecticide resistance have all contributed to the spread of CHIKV outbreaks. The very recent discovery of Aedes albopictus, a vector for CHIKV, and the first imported case of Chikungunya fever (CHIKF) in the south of France, as well as the recent outbreak in Italy in 2007, illustrate the potential for worldwide dissemination [12–14], making this virus a major threat to public health [15]. CHIKF is an acute illness. After a silent incubation period lasting 2–4 days, patients generally display an abrupt high fever, followed by skin rash and painful polyarthralgia. Symptoms may persist 3–7 days during the acute phase of the disease; however, chronic and incapacitating arthralgia can persist for months or even years [16]. Although CHIKF is not generally considered life-threatening, severe forms involving neurological and hepatological complications can occur, and fatalities were recently reported [17, 18]. Previous studies have focused mostly on the mosquito vectors [13, 17, 19–26], the genotyping and molecular characterization of CHIKV isolates, and outbreak epidemiology [1, 4–6, 27]. Few studies have focused on CHIKF pathogenesis. Three studies have attempted to correlate cytokine and chemokine profiles with CHIKF disease characteristics [28–30]. For instance, severe CHIKF has been linked to increased plasma levels of proinflammatory interleukins IL-12 and IL-6, as well as decreased levels of proinflammatory chemokine RANTES [28, 30]. A few other cytokines and chemokines have also been found to be upregulated during CHIKV infection (IL-7, IL-12, IP-10, MCP-1, IFN-α, and IFN-γ), although only a limited number of patients have been studied and at a unique time point during the acute phase [28–31]. Somewhat contradictory results have been published regarding the cytokines IL-1β and IL-10 [28, 30]. Virtually nothing is known about the mounting of adaptive immune responses to CHIKV infection. T and B lymphocytes and monocyte-derived dendritic cells are not susceptible to CHIKV infection [32] but their role in the clearance of infected cells or possibly in the pathogenesis of the disease remains completely unestablished. Furthermore, although CHIKV is known to induce apoptosis in vitro [16], the expression of markers of apoptosis ex vivo is still undocumented. Although the human immune response to CHIKV infection is poorly documented [28, 29, 32], the much more studied other members of the alphavirus genera bring some indications as to the possible interactions between CHIKV and the host's immune system. These studies show that the capacity of many alphaviruses to induce a severe disease is directly dependant on its ability to avoid or subvert the hosts' innate immunity. Type I Interferons (essentially IFN-α/β) are produced by most cell types and constitute the first line of defense against viral infections. Sindbis virus and Eastern equine encephalitis virus replication are strongly inhibited by IFN (types I and II) treatment [33–35], and in the absence of type I IFNs, the severity of Sindbis-induced disease is highly increased in animal models [33, 36]. A prominent role for type I IFNs in CHIKV clearance has also been suggested by both in vitro and animal models [32, 37]. Although the increasing impact of CHIKF in public health greatly exceeds that of other alphaviruses, immune responses to CHIKV infection have been neglected in comparison. Here, we conducted a large ex vivo study based on multiplex analysis of cytokine, chemokine, and growth factor plasmatic profiles of 69 CHIKF patients from the Gabonese outbreak of 2007. This is the largest cohort of CHIKF patients ever studied in this matter. Furthermore, we present phenotypic data on the T lymphocyte immune responses that occur during acute CHIKV infection in humans.

Two young girls without a notable medical history except for asthma presented with an acute toxic encephalopathy with very low serine concentrations both in plasma and cerebrospinal fluid (CSF) comparable to patients with 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency. Clinical symptoms and enzyme measurement (in one patient) excluded 3-PGDH deficiency. Deficiencies in other serine biosynthesis enzymes were highly unlikely on clinical grounds. On basis of the fasting state, ketone bodies and lactate in plasma, urine and CSF, we speculate that reduced serine levels were due to its use as gluconeogenic substrate, conversion to pyruvate by brain serine racemase or decreased L-serine production because of a lack of glucose. These are the first strikingly similar cases of patients with a clear secondary serine deficiency associated with a toxic encephalopathy.

International audience; The objective of this study was to investigate, under circumstances of routine care, the impact of paediatric delirium (PD) on length of stay in the paediatric intensive care unit (PICU) as well as on direct financial costs. A five-year prospective observational study (2002–2007) was carried out in a tertiary eight-bed PICU in the Netherlands. Critically ill children aged 1 to 18 years who were acutely, non-electively and consecutively admitted to the PICU and detected as having PD in routine care were compared to critically ill children aged 1 to 18 years without signs of PD. PD, population characteristics and severity of illness at admission were used as predictors for length of PICU stay. Differences in length of stay yielded short-term, direct medical costs associated with PD. Forty-nine children with and 98 children without PD were included. PD prolonged length of PICU stay with 2.39 days, independent of severity of illness, age, gender, mechanical ventilation and medical indication for admission ( = 0.38

The prevalence of hepatitis B virus (HBV) surface antigen was significantly higher in urban (12.9%) than in rural (7.6%) populations ( P = 0.003), but no difference was found in the prevalence of hepatitis delta virus (HDV), which was high in both populations. Phylogenetic analysis showed the circulation of HBV-A3 and -E genotypes and the presence of HDV-1, HDV-7, and HDV-8 clades.

Our aim was to evaluate a type 3 portable simplified device as a screening tool for obstructive sleep apnoea (OSA) in coronary patients.In 50 patients selected independently from sleep complaints, we compared the number of respiratory events per hour of valid recording time counted automatically by the device and the number counted manually per hour of sleep on polysomnography performed at home during the same night.Five patients were excluded because of technical failures. Estimated OSA prevalences (95% confidence interval) for apnoea/hypopnoea index (AHI) cut-offsor = 5,or = 15, andor = 30 by polysomnography were 0.93 (0.81-0.98), 0.69 (0.53-0.81), and 0.27 (0.15-0.42), respectively. The device would have correctly diagnosed 75% of patients with severe OSA (AHIor = 30 by polysomnography) and would have classified the remaining 25% as having moderate OSA.This ambulatory device may prove valuable in reducing the costs of diagnosing and managing OSA in coronary patients.

INTRODUCTION: Reduced concentrations of glucose-6-phospate dehydrogenase (G6PD) render erythrocytes susceptible to hemolysis under conditions of oxidative stress. In favism, the ingestion of fava beans induces an oxidative stress to erythrocytes, leading to acute hemolysis. DISCUSSION: The simultaneous occurrence of methemoglobinemia has been reported only scarcely, despite the fact that both phenomena are the consequence of a common pathophysiologic mechanism. The presence of methemoglobinemia has important diagnostic and therapeutic consequences. We report a previously healthy boy who presented with combined severe hemolytic anemia and cyanosis due to methemoglobinemia, following the ingestion of fava beans. His condition was complicated by the development of transient acute renal failure. A G6PD-deficiency was diagnosed. We review the literature on the combination of acute hemolysis and methemoglobinemia in favism. Pathophysiologic, diagnostic, and therapeutic aspects of this disorder are discussed.

International audience; We developed a mouse model of allergy to wheat flour gliadins, a protein fraction containing major wheat allergens. We compared the antibody responses (i.e., specific IgE and IgG1) and the profiles of cytokines secreted by reactivated splenocytes induced after intraperitoneal injections of gliadins in three strains of mice, namely, Balb/cJ, B10.A, and C3H/HeJ. The intensities of the allergic reactions elicited by intranasal challenge were also compared. Both the sensitization and elicitation were the highest in Balb/cJ mice, whereas weak or no reaction was observed in the others strains. Interestingly, the specificity of the mouse IgE against the different gliadins (i.e., alpha-, beta-, gamma-, omega 1,2-, and omega 5-gliadin) was similar to that observed in children allergic to wheat flour. Balb/cJ mice may thus provide a relevant model for the study of sensitization and elicitation by wheat gliadins and for improving our understanding of the specific role and mechanisms of action of the different classes of gliadins.

Hypospermia is a semen volume lower than 2 mL on at least two semen analyses. The etiologies of hypospermia are many and may be divided into two pathophysiologic sub-groups: disturbances of ejaculation reflex leading to partial retrograde ejaculation and seminal glands and ducts anatomic and functional anomalies. In this last pathologic mechanism, the mutations of CFTR gene, involved in many different forms of cystic fibrosis, represent a possible cause of hypospermia. The molecular anomaly of CFTR gene's screening is very important for the potential descendents and for the patient himself. It must be considered any time clinic and/or paraclinic context is evocative.

Delirium in children is a serious but understudied neuropsychiatric disorder. So there is little to guide the clinician in terms of identifying those at risk.To study, in a pediatric intensive care unit (PICU), the predictive power of widely used generic pediatric mortality scoring systems in relation to the occurrence of pediatric delirium (PD).Four-year prospective observational study, 2002-2005. Predictors used were the Pediatric Index of Mortality (PIM) and Pediatric Risk of Mortality (PRISM II).A tertiary 8-bed PICU in The Netherlands.877 critically ill children who were acutely, nonelectively, and consecutively admitted.Pediatric delirium.Out of 877 children with mean age 4.4 yrs, 40 were diagnosed with PD (Cumulative incidence: 4.5%), 85% of whom (versus 40% with nondelirium) were mechanically ventilated. The area under the curve was 0.74 for PRISM II and 0.71 for the PIM, with optimal cut-off points at the 60th centile (PRISM: sensitivity: 76%; specificity: 62%; PIM: sensitivity: 82%; specificity: 62%). A PRISM II or PIM score above the 60th centile was strongly associated with later PD in terms of relative risk (PRISM II: risk ratio = 4.9; 95% confidence interval: 2.3-10.1; PIM: RR = 6.7; 95% confidence interval: 3.0-15.0). Given the low incidence of PD, values for positive predictive value were lower (PRISM II: 8.3%; PIM: 8.9%, rising to, respectively, 10.1% and 10.6% in mechanically ventilated patients) and values for negative predictive value were higher (PRISM II: 98.3%; PIM: 98.7%).Given the relatively low incidence of delirium, a low detection rate biased toward the most severe cases cannot be excluded.Given the fact that PIM and PRISM II are widely used mortality scoring instruments, prospective associations with PD suggest additional value for ruling in, or out, patients at risk of PD.

SummaryWe describe four children with Dravet syndrome treated with the combination of valproic acid (VPA) and topiramate (TPM) who developed transient liver toxicity. The time-interval between fever, administration of acetaminophen, epileptic status and liver enzyme disturbances in our four cases suggests that accumulation of toxic acetaminophen-metabolites is possibly responsible for liver toxicity. If acetaminophen and its metabolites cause those liver problems in children treated with the combination of VPA and TPM, the advice to use acetaminophen for treating fever in children using this combination, should be changed. Only future clinical observations and research can solve this clinical dilemma.

Background Dengue virus (DENV) is the most prominent arbovirus worldwide, causing major epidemics in South-East Asia, South America and Africa. In 2010, a major DENV-2 outbreak occurred in Gabon with cases of patients co-infected with chikungunya virus (CHIKV). Although the innate immune response is thought to be of primordial importance in the development and outcome of arbovirus-associated pathologies, our knowledge of the role of natural killer (NK) cells during DENV-2 infection is in its infancy. Methodology We performed the first extensive comparative longitudinal characterization of NK cells in patients infected by DENV-2, CHIKV or both viruses. Hierarchical clustering and principal component analyses were performed to discriminate between CHIKV and DENV-2 infected patients. Principal Findings We observed that both activation and differentiation of NK cells are induced during the acute phase of infection by DENV-2 and CHIKV. Combinatorial analysis however, revealed that both arboviruses induced two different signatures of NK-cell responses, with CHIKV more associated with terminal differentiation, and DENV-2 with inhibitory KIRs. We show also that intracellular production of interferon-γ (IFN-γ) by NK cells is strongly stimulated in acute DENV-2 infection, compared to CHIKV. Conclusions/Significance Although specific differences were observed between CHIKV and DENV-2 infections, the significant remodeling of NK cell populations observed here suggests their potential roles in the control of both infections., Author Summary Dengue fever is the most important arthropod-borne viral disease worldwide, affecting 50 to 100 million individuals annually. The clinical picture associated with acute dengue virus (DENV) infections ranges from classical febrile illness to life-threatening disease. The innate immunity is the first line of defense in the control of viral replication. In this article, we examine the particular role of natural killer (NK) cells in DENV infection at different time points after the onset of symptoms. This extensive study was performed in comparison with patients infected by Chikungunya virus (CHIKV), another major arbovirus transmitted by the same mosquito vectors, and co-infected CHIKV/DENV-2 patients. We observed that DENV2 and CHIKV induced different signatures of NK-cell responses suggesting specific roles in the control of both infections.

Invasive aspergillosis is extremely rare in immunocompetent children. Here we describe the clinical, radiologic, and laboratory course of fatal invasive pulmonary and central nervous system aspergillosis in a previously healthy child after a near-drowning incident with submersion in a pond. Findings were compared with data from the literature, which is reviewed. Serum Aspergillus galactomannan levels were determined retrospectively and were compared with the results of routine microbiological and radiologic examinations, showing a significant diagnostic and therapeutic delay of the routine diagnostic approach in comparison with the use of the Aspergillus galactomannan assay. This delay may have contributed to the fatal course. Serial determination of serum Aspergillus galactomannan may be helpful in diagnosing invasive aspergillosis early in case of pulmonary disease after near-drowning and may contribute to an early appropriate treatment. Currently voriconazole, eventually in combination with caspofungin, should be considered as the drug of choice in the management of invasive aspergillosis after near-drowning.

Lymphocytic choriomeningitis virus (LCMV) can cause acute fatal disease on all continents but was never detected in Africa. We report the first detection of LCMV RNA in a common European house mouse ( Mus musculus domesticus ) in Africa. Phylogenetic analyses show a close relationship with North American strains. These findings suggest that there is a risk of the appearance of LCMV acute encephalitis cases. This is a perfect example of virus dissemination by its natural host that may have dramatic public health consequences.

International audience; African great apes are naturally infected by a multitude of Plasmodium species most of them recently discovered, among which several are closely related to human malaria agents. However, it is still unknown whether these animals can serve as source of infections for humans living in their vicinity. To evaluate this possibility, we analysed the nature of Plasmodium infections from a bank of 4281 human blood samples collected in 210 villages of Gabon, Central Africa. Among them, 2255 were detected positive to Plasmodium using molecular methods (Plasmodium Cytochrome b amplification). A high throughput sequencing technology (454 GS-FLX Titanium technology, Roche) was then used to identify the Plasmodium species present within each positive sample. Overall, we identified with confidence only three species infecting humans in Gabon: P. falciparum, P. malariae and P. ovale. None of the species known to infect non-human primates in Central Africa was found. Our study shows that ape Plasmodium parasites of the subgenus Laverania do not constitute a frequent source of infection for humans. It also suggests that some strong host genetic barriers must exist to prevent the cross species transmission of ape Plasmodium in a context of ever increasing contacts between humans and wildlife.

Ebolaviruses and Marburgviruses (family Filoviridae) are among the most virulent pathogens for humans and great apes causing severe haemorrhagic fever and death within a matter of days. This group of viruses is characterized by a linear, non-segmented, single-stranded RNA genome of negative polarity. The overall burden of filovirus infections is minimal and negligible compared to the devastation caused by malnutrition and other infectious diseases prevalent in Africa such as malaria, dengue or tuberculosis. In this paper, we review the knowledge gained on the eco/epidemiology, the pathogenesis and the disease control measures for Marburg and Ebola viruses developed over the last 15 years. The overall progress is promising given the little attention that these pathogen have achieved in the past; however, more is to come over the next decade given the more recent interest in these pathogens as potential public and animal health concerns. Licensing of therapeutic and prophylactic options may be achievable over the next 5-10 years.

Along the menstrual cycle and during pregnancy, small blood vessels proliferate within the uterus and the ovulating ovary. Angiogenic factors such as VEGF are involved in this phenomenon. In the ovulating ovary, neo-angiogenesis spreads progressively inside the dominant follicle wall and plays a role in the maintenance of the corpus luteum, under the influence of LH (or HCG during pregnancy). In ART, the measure of the blood flow is interesting since it correlates to the number and quality of harvested oocytes. Follicle hypoxia may impair chromosomal organization and separation within the oocyte. This neo-angiogenesis is also important in endometrium, in particular for embryo implantation. Ultrasounds with Doppler allow to estimate the endometrial receptivity, especially in IVF cycles. It is assumed that chance for ongoing pregnancy is almost zero if: endometrial thickness is 3. Doppler ultrasounds are a useful and even mandatory complement to standard vaginal ultrasonoghraphy in ART. It can be viewed as an indicator of the endometrial and follicular "well-being".

Study objective To evaluate the effect of carbon dioxide (CO 2 ) pneumoperitoneum and retropneumoperitoneum insufflation on CO 2 excretion. Design Prospective study. Setting Operating room and recovery room in a teaching hospital. Patients 29 patients scheduled for orthopedic spine fusion surgery. Interventions Patients received either transperitoneal insufflation (n = 12) or retroperitoneal insufflation (n = 17). Measurements and main results: Increases in the partial pressure of end-tidal CO 2 (PetCO 2 ) and arterial CO 2 tension (PaCO 2 ) during retropneumoperitoneum exceeded those obtained during pneumoperitoneum. Furthermore, PetCO 2 increased faster during retroperitoneum and did not reach a plateau. Finally, 76% of the patients in this group required ventilatory adjustment due to high PetCO 2 levels. Conclusions This study may focus attention on the need for continuous ventilatory adjustments during transperitoneal endoscopic surgery.

In 2010, a large outbreak of poliomyelitis with unusual 47% lethality occurred in Pointe Noire, Republic of Congo. Vaccine-mediated immunity against the outbreak virus was never investigated. A wild poliovirus 1 (WPV1) isolated from a fatal case (termed PV1-RC2010) showed a previously unknown combination of amino acid exchanges in critical antigenic site 2 (AgS2, VP1 capsid protein positions 221SAAL→221PADL). These exchanges were also detected in an additional 11 WPV1 strains from fatal cases. PV1-RC2010 escaped neutralization by three different mAbs relevant for AgS2. Virus neutralization was tested in sera from fatal cases, who died before supplementary immunization (n = 24), Gabonese recipients of recent oral polio vaccination (n = 12), routinely vaccinated German medical students (n = 34), and German outpatients tested for antipoliovirus immunity (n = 17) on Vero, human rhabdomyosarcoma, and human epidermoid carcinoma 2 cells. Fatal poliomyelitis cases gave laboratory evidence of previous trivalent vaccination. Neutralizing antibody titers against PV1-RC2010 were significantly lower than those against the vaccine strain Sabin-1, two genetically distinct WPV1s isolated in 1965 and 2010 and two genetically distinct vaccine-derived PV strains. Of German vaccinees tested according to World Health Organization protocols, 15–29% were unprotected according to their neutralization titers (

Chikungunya virus (CHIKV) is an alphavirus of the Togaviridae family that causes chronic and incapacitating arthralgia in human populations. Since its discovery in 1952, CHIKV was responsible for sporadic and infrequent outbreaks. However, since 2005, global Chikungunya outbreaks have occurred, inducing some fatalities and associated with severe and chronic morbidity. Chikungunya is thus considered as an important re-emerging public health problem in both tropical and temperate countries, where the distribution of the Aedes mosquito vectors continues to expand. This review highlights the most recent advances in our knowledge and understanding of the epidemiology, biology, treatment and vaccination strategies of CHIKV.