Search

We present a general experimental concept for jitter-free pump and probe experiments at free electron lasers. By generating pump and probe pulse from one and the same X-ray pulse using an optical split-and-delay unit, we obtain a temporal resolution that is limited only by the X-ray pulse lengths. In a two-color X-ray pump and X-ray probe experiment with sub 70 fs temporal resolution, we selectively probe the response of orbital and charge degree of freedom in the prototypical functional oxide magnetite after photoexcitation. We find electronic order to be quenched on a time scale of (30 ± 30) fs and hence most likely faster than what is to be expected for any lattice dynamics. Our experimental result hints to the formation of a short lived transient state with decoupled electronic and lattice degree of freedom in magnetite. The excitation and relaxation mechanism for X-ray pumping is discussed within a simple model leading to the conclusion that within the first 10 fs the original photoexcitation decays into low-energy electronic excitations comparable to what is achieved by optical pump pulse excitation. Our findings show on which time scales dynamical decoupling of degrees of freedom in functional oxides can be expected and how to probe this selectively with soft X-ray pulses. Results can be expected to provide crucial information for theories for ultrafast behavior of materials and help to develop concepts for novel switching devices.

Vacuum space charge induced kinetic energy shifts of O 1s and Ru 3d core levels in femtosecond soft X-ray photoemission spectra (PES) have been studied at a free electron laser (FEL) for an oxygen layer on Ru(0001). We fully reproduced the measurements by simulating the in-vacuum expansion of the photoelectrons and demonstrate the space charge contribution of the high-order harmonics in the FEL beam. Employing the same analysis for 400 nm pump-X-ray probe PES, we can disentangle the delay dependent Ru 3d energy shifts into effects induced by space charge and by lattice heating from the femtosecond pump pulse.

One of the most challenging tasks for extreme ultraviolet, soft and hard x-ray free-electron laser photon diagnostics is the precise determination of the photon pulse duration, which is typically in the sub 100 fs range. Nine different methods, able to determine such ultrashort photon pulse durations, were compared experimentally at FLASH, the self-amplified spontaneous emission free-electron laser at DESY in Hamburg, in order to identify advantages and disadvantages of different methods. Radiation pulses at a wavelength of 13.5 and 24.0 nm together with the corresponding electron bunch duration were measured by indirect methods like analyzing spectral correlations, statistical fluctuations, and energy modulations of the electron bunch and also by direct methods like autocorrelation techniques, terahertz streaking, or reflectivity changes of solid state samples. In this paper, we present a comprehensive overview of the various techniques and a comparison of the individual experimental results. The information gained is of utmost importance for the future development of reliable pulse duration monitors indispensable for successful experiments with ultrashort extreme ultraviolet pulses.

Belt drives work often with short center distances and very different wrap arcs so that high adherence characteristics are required at the belt-pulley contact. In addition, the belt flexural stiffness reduces the contact width, but this decrease may be compensated in part by the belt softening due to the shear compliance. [ABSTRACT FROM AUTHOR]

WHICH ARE SOMATIC DISEASES OF MIGRANT CHILDREN? Migrant children form a vulnerable and heterogeneous population estimated at 70 000 in France. Their health is influenced by their living conditions in their home country, stress and exposure to pathogens, unsanitary housing and food insecurity during their migratory route and in their host country, as well as their parents psychological disorders. They present malnutrition, nutritional de¬ficiencies (iron and vitamin D), various dental, skin and intestinal infections, a significant prevalence of tuberculosis, and sometimes imported parasitic infections (malaria, schistosomiasis…) and lead poisoning. An high prevalence of early neurodevelopmental pro¬blems is noticed. Their immunity is insufficient and catch-up vacci¬nation is most often necessary. They require the support of a socio-psycho-medico-educational care network., Competing Interests: Les auteurs déclarent n’avoir aucun lien d’intérêts.

Competing Interests: L’auteure déclare n’avoir aucun lien d’intérêts.

Competing Interests: Les auteurs déclarent ne pas avoir de liens d’intérêts.

Competing Interests: L’auteur déclare n’avoir aucun lien d’intérêts.

Background and Aims: Healthcare for the increasing number of migrants in Europe, and particularly of unaccompanied minors (UMs) seeking asylum, has become a major challenge. We aimed to describe the health issues of UMs managed in a dedicated pediatric consultation service in a care center in Paris., Methods: All UMs attending a dedicated migrant medical consultation service in Robert Debré Hospital, Paris, France, were included in a single-center retrospective observational study from September 1, 2017, to September 30, 2018., Results: Out of the 107 UMs who were included, 87% had a health problem (n=93) and 52% had an infectious disease (n=56). The main infectious diagnoses were schistosomiasis (22%), latent tuberculosis (22%), intestinal parasitosis (16%), and chronic hepatitis B (8%). Posttraumatic stress disorder (PTSD) and overweight were common (35% and 20%, respectively). The median age was 15 years old (IQR, 14-16), the male/female ratio was 95/12. Most of the children were from sub-Saharan Africa (n=67), 46% had crossed Libya (n=49) and, when compared to the other migration routes, faced an increasing risk of violence (69%, p=0.04), imprisonment (53%, p=0.03), and forced labor (48%, p=0.02). The median duration of the trip before reaching France was 6 months (IQR, 2-13), the median time to consultation was 2 months (0-5) and was not associated with an increased risk of health problems. A total of 43 UMs were lost to follow-up., Conclusion: Health problems, particularly infectious diseases and PTSD, are common among UMs and should prompt an early medical consultation with psychiatric evaluation. Follow-up is problematic and could be improved by an on-line health book., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Background: There are few data on imported schistosomiasis - especially in children. The objectives of the present study were to estimate the prevalence of imported schistosomiasis in at-risk children in the greater Paris region of France and to compare diagnostic methods., Method: Children at risk of schistosomiasis who consulted or were hospitalized in four hospitals in the greater Paris region were prospectively included. Clinical and laboratory data were collected. Urine and feces samples were screened for Schistosoma spp. using microscopy, a point-of-care circulating cathodic antigen and a real-time polymerase chain reaction assay. Serum samples were screened using Western blot, ELISA, indirect hemagglutination, and immunochromatographic assays. The diagnosis was characterized as confirmed (positive microscopy analysis) and as suspected (positive ELISA and Western blot assays). The prevalence of schistosomiasis and the tests' performances were estimated using the latent class method., Results: A total of 114 children were included. Most of the children were newly arrived migrants from sub-Saharan Africa. The mean age was 13.2 years-old. There were 12 (10.5%) confirmed cases and 13 (11.4%) suspected cases. Half of the confirmed and suspected cases were asymptomatic. The prevalence was 24.3%. The ELISA and the Western blot assays presented the same sensitivity (83%) and specificity (99%). The serum immunochromatographic assay also showed good performance., Conclusions: The high prevalence of imported schistosomiasis among at-risk children in the greater Paris region confirms the need for systematic screening. A serum immunochromatographic assay appears to be one of the most effective screening methods for a low cost., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Sickle cell disease (SCD) children are frequent travellers to countries where yellow fever (YF) is endemic, but there are no data regarding the safety and immunogenicity of the vaccine in such children treated with hydroxyurea (HU). The main objective of this study was to compare the tolerance and immune response to YF vaccination in SCD children treated or not with HU., Method: SCD children < 18 years attending the international travel clinics of three large paediatric centres and requiring a first YF vaccination were included in a prospective study. Adverse events were collected 2 weeks after vaccination. YF vaccine antibody titres were measured ~6 months after vaccination., Results: Among the 52 SCD children vaccinated against YF, 17 (33%) were treated with HU. Only mild adverse events, mainly fever and local reaction, were observed in the HU group with a similar frequency in the non-HU group (57 and 35%, respectively, P = 0.30). YF antibody titres were measured in 15/17 patients in the HU group and 23/35 patients in the non-HU group after a median of 6.0 months (3.5-8.5) following vaccination. The geometric mean of YF antibody titre was similar in both groups. A protective antibody level was observed in 85% of the children in the HU group vs 100% in the non-HU group (P = 0.14), suggesting a lower effectiveness of the vaccine in patients on HU similarly to what has been described in patients on immune suppressive therapy for other vaccines., Conclusion: YF vaccination seems to be safe and efficient in SCD children treated with HU. Considering the potential risk of severe complications in cases of YF while travelling in Africa for those patients, the benefit-to-risk ratio argues for YF vaccination in all SCD children. Control of a protective antibody titre may also be useful to ascertain an adequate response in those treated with HU., (© International Society of Travel Medicine 2021. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Aim: In the context of global changes in the epidemiology of internationally adopted children (IACs), the prevalence of infectious diseases and nutritional impairment has not been recently reviewed. Moreover, in France, these characteristics of the children according to their continents of origin and preadoption special needs (SN) status have been incompletely explored., Methods: Demographic, infectious data and anthropometric of all the newly arrived IACs seen in a specialised clinic for international adoptees in Paris, France, between 2013 and 2016 were retrospectively reviewed., Results: Three hundred and fifty IACs [mean age: 3.4 years (±2.7), 204 male] from 39 countries were included; 55% had SN. Ninety-nine patients had at least one infection, 42% being classified as 'serious' (chronic viral infection, tuberculosis or malaria). Chronic viral infection was diagnosed in 26 (7%) patients (HIV: 16 cases, HBV: 5, HCV: 4) and affected especially Asian children (P < .001). The prevalence of stunting, underweight, wasting and microcephaly was, respectively, 25%, 22%, 15% and 8%. Stunting was more frequent in children from Eastern Europe (P = .02), while SN children were more often microcephalic or underweight (respectively P = .03 and .02)., Conclusion: The prevalence of serious infections and nutritional impairment remains high in IACs and requires early detection and careful follow-up., (©2020 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Erythropoietic protoporphyria (EPP) is a rare inherited disease associated with heme metabolism, characterized by severe life-long photosensitivity and liver involvement., Objective: To provide epidemiological data of EPP in Italy., Materials & Methods: Prospective/retrospective data of EPP patients were collected by an Italian network of porphyria specialist centres (Gruppo Italiano Porfiria, GrIP) over a 20-year period (1996-2017)., Results: In total, 179 patients (79 females) with a clinical and biochemical diagnosis of EPP were assessed, revealing a prevalence of 3.15 cases per million persons and an incidence of 0.13 cases per million persons/year. Incidence significantly increased after 2009 (due to the availability of alfa-melanotide, which effectively limits skin photosensitivity). Mean age at diagnosis was 28 years, with only 22 patients (12.2%) diagnosed ≤10 years old. Gene mutations were assessed in 173 (96.6%) patients; most (164; 91.3%) were FECH mutations on one allele in association with the hypomorphic variant, c.315-48C, on the other (classic EPP), and nine (5.2%) were ALAS2 mutations (X-linked EPP). Only one case of autosomal recessive EPP was observed. Of the 42 different FECH mutations, 15 are novel, three mutations collectively accounted for 45.9% (75/164) of the mutations (c.215dupT [27.2%], c.901&#95;902delTG [11.5%] and c.67 + 5G > A [7.2%]), and frameshift mutations were prevalent (33.3%). A form of light protection was used by 109/179 (60.8%) patients, and 100 (56%) had at least one α-melanotide implant. Three cases of severe acute liver involvement, requiring OLT, were observed., Conclusion: These data define, for the first time, the clinical and molecular epidemiology of EPP in Italy.

Prevention of malaria is based on personal vector-control measures (PVCMs) to avoid mosquito bites at night and chemoprophylaxis if justified by the risk of contracting the disease. The most effective PVCM is the use of insecticide-treated mosquito nets. The decision to prescribe chemoprophylaxis, mainly to prevent Plasmodium falciparum infection, depends on the benefit-risk ratio. Overall, the risk of contracting malaria is 1,000-fold lower during a stay in the tropical regions of Asia or the Americas than in sub-Saharan Africa. For "conventional" stays (less than one month with nights spent in urban areas) in low-risk settings in tropical Asia and America, the risk of being infected with Plasmodium parasites (≤1/100,000) is equivalent or lower than that of experiencing serious adverse effects caused by chemoprophylaxis. Preventive medication is therefore no longer recommended. By contrast, in other settings and particularly in sub-Saharan Africa, chemoprophylaxis is the most effective measure against malaria. However, it is worth noting that no single preventive measure provides full protection. Regardless of the level of risk or chemoprophylaxis-related indication, protection against mosquito bites and rapid management of febrile illness after returning from an endemic area are also critical to prevent malaria. Finally, migrants of sub-Saharan origin visiting friends and relatives in their country of origin form a high-risk group who should be recommended chemoprophylaxis in the same way as any other travelers-with a preference for the least expensive molecules (doxycycline)., (Copyright © 2019. Published by Elsevier Masson SAS.)

Since the 2007 French guidelines on imported Falciparum malaria, the epidemiology, treatment, and prevention of malaria have changed considerably requiring guidelines for all Plasmodium species to be updated. Over the past decade, the incidence of imported malaria has decreased in all age groups, reflecting the decrease in the incidence of malaria in endemic areas. The rates of severe pediatric cases have increased as in adults, but fatalities are rare. The parasitological diagnosis requires a thick blood smear (or a rapid immunochromatographic test) and a thin blood film. Alternatively, a rapid antigen detection test can be paired with a thin blood film. Thrombocytopenia in children presenting with fever is highly predictive of malaria following travel to a malaria-endemic area and, when detected, malaria should be strongly considered. The first-line treatment of uncomplicated P. falciparum malaria is now an artemisinin-based combination therapy (ACT), either artemether-lumefantrine or artenimol-piperaquine, as recommended by the World Health Organization in endemic areas. Uncomplicated presentations of non-falciparum malaria should be treated either with chloroquine or ACT. The first-line treatment of severe malaria is now intravenous artesunate which is more effective than quinine in endemic areas. Quinine is restricted to cases where artesunate is contraindicated or unavailable. Prevention of malaria in pediatric travelers consists of nocturnal personal protection against mosquitoes (especially insecticide-treated nets) combined with chemoprophylaxis according to the risk level., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Criminal investigations of suspected murder cases require estimating the post-mortem interval (PMI, or time after death) which is challenging for long PMIs. Here we present the case of human remains found in a Swiss forest. We have used a multidisciplinary approach involving the analysis of bones and soil samples collected beneath the remains of the head, upper and lower body and "control" samples taken a few meters away. We analysed soil chemical characteristics, mites and nematodes (by microscopy) and micro-eukaryotes (by Illumina high throughput sequencing). The PMI estimate on hair 14 C-data via bomb peak radiocarbon dating gave a time range of 1 to 3 years before the discovery of the remains. Cluster analyses for soil chemical constituents, nematodes, mites and micro-eukaryotes revealed two clusters 1) head and upper body and 2) lower body and controls. From mite evidence, we conclude that the body was probably brought to the site after death. However, chemical analyses, nematode community analyses and the analyses of micro-eukaryotes indicate that decomposition took place at least partly on site. This study illustrates the usefulness of combining several lines of evidence for the study of homicide cases to better calibrate PMI inference tools.

We investigated the knowledge of female genital mutilation (FGM) among 60 general and 52 specialized travel medicine practitioners. Less than 50% of these practitioners had adequate knowledge of FGM. Only 42.9% declared having encountered FGM. FGM is likely underestimated in health facilities. Medical education and supporting information should be developed to better address and prevent FGM., (© International Society of Travel Medicine, 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Dengue is the arboviral disease that has massively spread in intertropical regions these past few years. The rise in imported cases of dengue and the rapid spread of the Aedes vector mosquitoes in continental France since 2004 explain the occurrence of indigenous dengue cases among the nonimmune population and points to an epidemic risk. Severe dengue cases are rare, but lethality is highest among children under 5 years of age. Like pediatricians in tropical regions, we must learn how dengue presents in metropolitan France and how it can be managed, and pay special attention to severe and potentially fatal forms. The epidemiological, pathophysiological, clinical, diagnostic, and therapeutic characteristics of dengue are presented herein., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: The number of trips to the tropics taken by children with chronic health disorders (CHDs) is increasing., Methods: All of the children with CHDs who attended two international vaccination centres in France before travelling to the tropics were included in a prospective, exposed/unexposed study. Each child was age-matched with two control children and followed for 1 month after returning from the tropics., Results: Fifty-six children with CHDs and 107 control children were included. The children's median age was 6 years old (IQR 2-11). Of the study participants, 127/163 (78%) travelled to West Africa, mainly to visit relatives. The median duration of the stay was 42 days (IQR 31-55). The age of the children, the destination and the duration of the trip were similar between the two groups. Sickle cell disease (23/56) and asthma (16/56) were the most common CHDs. Overall, the children with CHDs experienced more clinical events than the control patients did (p<0.05); however, there was no difference when chronic disease exacerbations were excluded (p=0.64) or when only the period abroad was considered (p=0.24). One child with a recent genetic diagnosis of atypical haemolytic uraemic syndrome died from a first disease exacerbation., Conclusions: Health problems among children with CHDs travelling abroad are mainly related to chronic disease exacerbations, which mostly occur after the children return. Patients with diseases that require highly specialised care for an exacerbation should avoid travelling to resource-limited tropical countries., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Child travelers are numerous, exposed to the risk of diseases, both infectious and noninfectious, for which practitioners often lack experience. The assessment of febrile returning child travelers is becoming more frequent and challenging. The question of previous travel should be foremost in the checklist of the interview of any febrile child traveler, because this implies a possible tropical disease such as malaria that may be life-threatening. These need to be investigated and treated effectively and rapidly. There are highly contagious infections that could pose public health risks requiring implementation of hygienic and public health measures. A detailed immunization, medical, and travel history for exposure to infectious risks using geographic, seasonal, environmental, sociocultural, and epidemiological data are needed. Along with clinical examination and elementary first-line investigations, the history should guide second-line exams, which will provide the etiology and optimal treatment in approximately 75 % of cases. The majority of children will have a cosmopolitan infection that resolves spontaneously or is simple to treat. Malaria will need urgent and specific treatment. This article describes guidance on first-line evaluation and management of febrile child travelers as recommended in France., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The DevelopAKUre project is underway to test nitisinone as a specific treatment to counteract this derangement of the phenylalanine-tyrosine catabolic pathway. We analysed DNA of 40 AKU patients enrolled for SONIA1, the first study in DevelopAKUre, and of 59 other AKU patients sent to our laboratory for molecular diagnostics. We identified 12 novel DNA variants: one was identified in patients from Brazil (c.557T>A), Slovakia (c.500C>T) and France (c.440T>C), three in patients from India (c.469+6T>C, c.650-85A>G, c.158G>A), and six in patients from Italy (c.742A>G, c.614G>A, c.1057A>C, c.752G>A, c.119A>C, c.926G>T). Thus, the total number of potential AKU-causing variants found in 380 patients reported in the HGD mutation database is now 129. Using mCSM and DUET, computational approaches based on the protein 3D structure, the novel missense variants are predicted to affect the activity of the enzyme by three mechanisms: decrease of stability of individual protomers, disruption of protomer-protomer interactions or modification of residues in the region of the active site. We also present an overview of AKU in Italy, where so far about 60 AKU cases are known and DNA analysis has been reported for 34 of them. In this rather small group, 26 different HGD variants affecting function were described, indicating rather high heterogeneity. Twelve of these variants seem to be specific for Italy.

Background: In erythropoietic protoporphyria (EPP), an inherited disease of porphyrin-biosynthesis, the accumulation of protoporphyrin in the skin causes severely painful phototoxic reactions. Symptom prevention was impossible until recently when afamelanotide became available. Afamelanotide-induced skin pigmentation has statistically significantly improved light-tolerance, although the clinical significance of the statistical effect was unknown., Objectives: To assess clinical effectiveness by recording compliance and safety during prolonged use., Methods: We report longitudinal observations of 115 ambulatory patients with EPP, who were treated with a total of 1023 afamelanotide implants over a period of up to 8 years at two porphyria centres; one in Rome, Italy, and the other in Zurich, Switzerland., Results: Since the treatment first became available in 2006, the number of patients treated with 16 mg afamelanotide implants rose continuously until June 2014, when 66% of all patients with EPP known to the porphyria centres were treated. Only three patients considered afamelanotide did not meet their expectations for symptom improvement; 23% discontinued the treatment for other, mostly compelling, reasons such as pregnancy or financial restrictions. The quality of life (QoL) scores, measured by an EPP-specific questionnaire, were 31 ± 24% of maximum prior to afamelanotide treatment, rose to 74% after starting afamelanotide and remained at this level during the entire observation period. Only minor adverse events attributable to afamelanotide, predominantly nausea, were recorded., Conclusion: Based on the improved QoL scores, high compliance and low discontinuation rates, we conclude that afamelanotide exhibits good clinical effectiveness and good safety in EPP under long-term routine conditions., (© 2014 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Hereditary hemochromatosis (HH) is a heterogeneous disorder of iron metabolism. The most common form of the disease is Classic or type 1 HH, mainly caused by a biallelic missense p.Cys282Tyr (c.845G>A) mutation in the HFE gene. However, the penetrance of p.Cys282Tyr/p.Cys282Tyr genotype is incomplete in terms of both biochemical and clinical expressivity. Lack of penetrance is thought to be caused by several genetic and environmental factors. Recently, a lot of evidences on HH genetic modifiers were produced, often without conclusive results. We investigated 6 polymorphisms (rs10421768 in HAMP gene, rs235756 in BMP2 gene, rs2230267 in FTL gene, rs1439816 in SLC40A1 gene, rs41295942 in TFR2 gene and rs2111833 in TMPRSS6 gene) with uncertain function in order to further evaluate their role in an independent cohort of 109 HH type 1 patients. Our results make it likely the role of rs10421768, rs235756, rs2230267 and rs1439816 polymorphisms, respectively in HAMP, BMP2, FTL and SLC40A1 genes in HH expressivity. In addition, previous and our findings support a hypothetical multifactorial model of HH, characterized by a principal gene (HFE in HH type 1) and minor genetic and environmental factors that still have to be fully elucidated., (Copyright © 2015. Published by Elsevier Inc.)

Consultation of child traveler has two main objectives: to assess of health risk related to the child's health status and history and also the risk related to travel environment; to counsel and prescribe preventive measure to reduce these travel health risks. The evaluation is based on physical examination and a detailed interview including personal history and information regarding the regions of proposed travel. Up to date knowledge of the epidemiology of visited sites, preventive measures and presumptive treatment is required. Essential health recommendations include, in case of exposure, prevention of malaria, arthropod borned diseases and vaccine preventable diseases. For all destinations advice regarding prevention of diarrhea, accident risks and aggravation of preexisting chronic diseases is needed. Universal primary prevention counselling is valuable for all travellers regardless of their age. In the case of children, special attention must be given to food and water hygiene, sun and heat exposure, swimming risks and transports security measures. Evaluation of risk and health education take time and often several visits are needed to complete the immunization schedule before departure., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Use of topical insect repellent is an important component in prophylaxis of arthropod bite vector borne diseases. Topical insect repellent are used in a three part management regimen, along with impregnated clothing and mosquito netting. Parental training for efficacious and secure use of repellents for their children is essential part of a successful strategy to combat Lyme borreliosis, dengue fever, Chikungunya, West Nile virus infection and malaria, amongst children, according to local epidemiological risks. Rational repellent prescription for a child must take into account age, active substance concentration, topical substance tolerance, nature and surface of the skin to protect, number of daily applications, and the length of use in a benefit-risk ratio assessment perspective. The 4 currently repellents recommended by Whopes (Who) for their long lasting efficacy and patient tolerance are: 1) Citriodiol (PMD), 2) DEET, 3) Icaridine (KB3023), and 4) IR3535. In field trials the minimum required concentration of each four of these agents to be effective for 3 hours against most arthropods is 20% (in cream, roll-on or spray vehicle). Described side effects of these agents are mild, being limited to local irritative dermatitis and allergy. The risk of severe side effects has been related to DEET misused and neurotoxicity. The international recommendations concerning utilization of topical repellent amongst children for prophylaxis of arthropod borne diseases is concerning short term usage (several weeks). But the use of repellent is sub chronic or chronic amongst the majority of children living in subtropical regions where these vector borne diseases are endemic. And toxicity of topical repellent when used sub-chronically and chronically is not well studied in pediatric age groups. Taking into account these considerations, the current recommendations of the French Group of Tropical Paediatrics are to teach the parents of children who live in arthropod vector disease endemic regions to use topical insect repellent on their children with the recommended age related frequency in the following way: the use of topical repellent in infants above 6 months, once daily. Only in exceptional circumstances of severe arthropod exposure risk, their brief use in nursing infants as young as 2 months is acceptable, however with never more than 1 application daily. From ages 1 to 12 years, 2 applications daily may be safely used; 3 applications daily after 12 years old through adulthood.

Here we report the characterization of four novel mutations and a previously described one of the coproporphyrinogen III oxidase (CPO) gene in five Italian patients affected by Hereditary Coproporphyria (HCP). Three of the novel genetic variants are missense mutations (p.Gly242Cys; p.Leu398Pro; p.Ser245Phe) and one is a frameshift mutation (p.Gly188TrpfsX45).

Each year hundreds of thousands of children leave France to travel to developing countries where they are exposed to infectious agents that can be prevented by vaccination. During the child's pre-travel check-up, practitioners should check that all mandatory immunizations are up-to-date and provide advice on relevant vaccines in function of the epidemiological situation at the chosen destination. However various factors hinder full compliance with this approach and some vaccines are underused. Underused vaccines are referred to as neglected vaccines. In the French vaccination schedule three vaccinations can be considered as neglected. The first is the hepatitis B vaccine that has a low coverage level in France due to strong reluctance to its use despite the fact that the virus is widespread in tropical areas. The second is pneumococcal vaccine that should be administered to all infants less than 2 years of age, especially for travel to areas where pneumonia and meningitis are frequent. The third is BCG vaccine that is now at greater risk of being neglected in child travellers because its use has been downgraded from a general requirement to a recommendation only for children at risk. A serious limitation on the use of travel vaccinations is cost that can lead families to neglect some infectious risk such as hepatitis A that is a major risk for child travellers as well as for their relatives during or after the trip and typhoid fever that is essentially an imported disease. Rabies vaccine is also underused due to its cost and to poor understanding of the risk by many practitioners and families. The purpose of this article is to underline the need to improve information and access to vaccines that are all too often neglected in child travellers.

Aims: Neointima formation after vascular injury is strongly associated with inflammation. Rapamycin inhibits human neointima formation and reduces expression of the proinflammatory cytokine endothelial-monocyte activating peptide II (EMAP-II) in vitro. Here we investigated the interplay between EMAP-II and rapamycin after vascular injury in vivo., Methods and Results: In a mouse model of vascular injury, mice were either not treated, given everolimus, a rapamycin derivate, or subjected to simultaneous challenge with everolimus and EMAP-II. EMAP-II expression was measured in coronary artery smooth muscle cells (CASMC) and monocytic cells in vitro and in patients after percutaneous coronary intervention (PCI). After vascular injury, rapamycin reduced neointima formation and adventitial thickening. Immunohistochemistry revealed reduced EMAP-II protein expression and suppressed recruitment of inflammatory cells. Simultaneous challenge with EMAP-II counteracted these effects of rapamycin. Expression of EMAP-II and its inhibition by rapamycin was confirmed in CASMC and monocytic cells. In patients, EMAP-II upregulation was confined to PCI of distal coronary artery segments and profoundly suppressed by oral rapamycin treatment., Conclusion: These data suggest important yet unrecognized roles of EMAP-II and adventitial inflammation in neointima formation: Through inhibition of EMAP-II, rapamycin reduces the recruitment of inflammatory cells to the adventitia and supports an early and bland healing.

Vector transmitted diseases are often a serious threat for child health, especially for children traveller in tropical regions. Few arthropod borne diseases are preventable by immunization or chimioprophylaxis. Prevention of most of them is based on personal protection against arthropod bites. The evidence of its efficacy has been established by the use of impregnated bed nets, impregnated clothes with permethrin or mosquito repellent which reduced significantly child malaria morbidity and mortality in endemic countries. These personal protective measures are able to minimize arthropod bites and prevent Chikungunya infection, dengue fever and Lyme disease. The choice of a repellent among the commercialised products need to be efficacy and safety evidence based. This article propose to raise this issue and to give pragmatic recommendations, with a focus to children below 30 months who are at a high toxicological risk. Severity of these diseases allowed to use potentially toxic repellents if misused.

Mutations and a low-expressed allele IVS3-48c (in trans to the mutation) of the ferrochelatase (FECH) gene are responsible for erythropoietic protoporphyria (EPP) which is characterized clinically by cutaneous photosensitivity. In this study of 15 Italian EPP families, we identified 10 different FECH gene mutations, six of them were novel mutations (Q32X; IVS2-2, a-->g; IVS3-67, g-->a; 488-501del 14bp; IVS5-3, c-->t and 757-761delAGAAG). Four were known mutations (213insT; R115X; S264L and 899-900delTG). Real-time PCR quantification of FECH mRNA from a patient carrying mutation IVS-67, g-->a revealed a 51% reduction in the normal FECH transcript. This mutation generated an abnormal mRNA species with a 63-bp intron 3 retention--the same mRNA species which the low-expressed FECH allele IVS3-48c also produces. In addition, a double intronic deletion (IVS8-61 del ag /IVS9-58 del a) was found in some patients as well as their healthy relatives of this cohort. Sequencing of 50 Italian control subjects revealed an 11% prevalence of the double deletion. However, the double intronic deletion is not a disease-causing mutation as evidenced by a normal amount of FECH mRNA measured from a non-porphyric individual who carried the double deletion. Another interesting finding of this study was a 1% prevalence of IVS3-48c allele in the white Italian population, comparing to 11% in the French population. Further epidemiological studies are needed to test whether the 1% frequency of the low-expressed IVS3-48c allele is associated with a low prevalence of EPP in the white Italian population.

Each year, half a million of children leave France to travel towards countries south or east of the European Union, sometimes in poor sanitary conditions. In order to propose essential or useful immunizations for these trips, the current synthesis will allow the practitioner to insure that the routine French immunization schedule has been followed, and to complete it if needed, to protect the child according to the epidemiological situation in the visited area, to try to reduce the limitations of the immunization of the traveler child. In case of emergency, or close departure, it may be useful to follow an accelerated schedule of the last minute, and, sometimes, to immunize traveler children with a chronic disease. Informations on Internet sites useful for the knowledge of current infectious risks in the destination country are also provided.

The accumulation of smooth muscle and endothelial cells is essential for remodeling and repair of injured blood vessel walls. Bone marrow-derived progenitor cells have been implicated in vascular repair and remodeling; however, the mechanisms underlying their recruitment to the site of injury remain elusive. Here, using real-time in vivo fluorescence microscopy, we show that platelets provide the critical signal that recruits CD34+ bone marrow cells and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells to sites of vascular injury. Correspondingly, specific inhibition of platelet adhesion virtually abrogated the accumulation of both CD34+ and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells at sites of endothelial disruption. Binding of bone marrow cells to platelets involves both P-selectin and GPIIb integrin on platelets. Unexpectedly, we found that activated platelets secrete the chemokine SDF-1alpha, thereby supporting further primary adhesion and migration of progenitor cells. These findings establish the platelet as a major player in the initiation of vascular remodeling, a process of fundamental importance for vascular repair and pathological remodeling after vascular injury.

Context and Objectives: Imported P. falciparum malaria cases are rising in France reaching 1300 estimated children in 2000. Three years after the publication of therapeutic guidelines, the Groupe de Pédiatrie Tropicale conducted an observational survey in order to describe the practice of acute uncomplicated malaria treatments in children, to identify their limits and to make proposals to improve them., Methods: A self administrated questionnaire has been proposed to 29 pediatric wards declaring over 10 malaria cases in 2000. Questions were focused on treatment practices and monitoring of children diagnosed with acute uncomplicated malaria in 2002., Results: Twenty-six services, who treated more than 700 children, responded. Twenty-two on 26 services hospitalized systematically malaria cases. Mean duration of hospitalization was 2.2 days (S.D. +/- 0.9). First line treatment was halofantrine in 22 on 26 services and mefloquine in four services. A second halofantrine dose was given systematically at day 7 in three services. No clinical cardiac effects happened. Quinine was used in perfusion only in cases of gastric intolerance. Treatment failure has never been experienced in the 22 services using halofantrine and has been experienced at least once in two on four wards using mefloquine. Relapse occurred at least once in 19 on 22 wards treating with halofantrine., Discussion: Halofantrine with hospitalization is still the leading treatment of acute uncomplicated malaria in children in France. In spite of the absence of clinical cardiac incident, a second cure of halofantrine was not often used, exposing to a high rate of relapse. Mefloquine is three time more used than in 1997, in spite of its digestives side effects that can explain failures of treatment. When done, the systematic clinical and parasitological control confirms failures after mefloquine and the high incidence of relapse after one cure of halofantrine. Only used in case of severity or digestive disorders, quinine is a little less prescribed in acute uncomplicated malaria in 2001 than in 1997., Conclusions: The limitations of antimalarial drugs used in France in case of acute malaria argue for an improvement of protocols (systematic second reduced dose of halofantrine after day 7, mefloquine associated with antiemetic drug) and a systematic clinical and parasitological monitoring. As alternative, efficient combinations of antimalarial as first line treatment are needed in France.

Objective: Dropouts are frequent among eating disorder (ED) patients, but less is known about their natural history. This paper assesses the outcome of outpatients who dropped out from a therapy programme and its possible causes., Material and Methods: From 1992 to 1994, we assessed 222 ED subjects. Psychiatrists expert in EDs evaluated these subjects by defining baseline parameters and diagnosis was made according to the 3rd revisioned edition of the Diagnostic and Statistical Manual of Mental Disorders. One hundred and twenty-eight subjects (57%) dropped out during the treatment. In 1997, we contacted them, reassessed the same baseline parameters and asked for a self-judgment about their social and clinical condition during the previous 2-5 years. Patients were classified as "improved" and "not improved" (stationary or worse) according to their social, physical and psychological condition. The relation between baseline condition and outcome was determined statistically., Results: Seventy-one percent of subjects were "improved" and no deaths were recorded. A significant correlation was found between "duration of illness" and no treatment following a dropout., Discussion: The high percentage of improvement among dropouts was unexpected. Shorter duration of illness and lack of specific therapy in the improved patients suggest the existence of a subset of ED patients with acute onset and a spontaneous tendency to improve. This point obviously requires further investigation.

Aim: To investigate the feasibility and efficacy of hepatitis C virus screening in drug users in an addiction out-patient unit., Patients and Methods: All patients followed in an addiction out-patient unit were asked to undergo anti-hepatitis C virus antibody testing; further evaluation and treatment if indicated, were offered to positive patients. When treatment was initiated (Metavir score >=F2), patients were followed-up both by the hepatologist and the out-patient unit physician., Results: Between July 1997 and September 2000, 404 consecutive patients (310 men, mean age: 32, alcohol intake >=50 g per day in 51%, 94% in opiate substitution program) were included. Sixty-six per cent (269/404) of patients agreed to undergo HCV antibodies testing: 84% had a positive test. 68% of these patients accepted ALT serum measurement and 120 had indications for liver biopsy. Eighty-eight liver biopsies were performed, showing severe fibrosis (Metavir score F3 or F4) in 20 cases (22%). Ethanol intake was significantly correlated to fibrosis (P<0.05). Antiviral treatment was indicated in 47 patients but was only initiated in 27 due to patient refusal (n=7) or contraindication (n=13). Treatment had to be discontinued in 12 cases because of psychiatric side effects (depression: n=3; delirium: n=3; severe irritability: n=3; relapse with heroin injection: n=3). Finally, only 5 patients were sustained responders., Conclusion: Despite the high seroprevalence of HCV antibodies in this unit, the benefits of antiviral therapy are low due to high drop out rate. Ethanol withdrawal should be the highest priority in these patients.

We have compared the migraine-inducing effect of nitroglycerin ointment applied to the frontotemporal region of the head, which is innervated by the ophthalmic and maxillary divisions of the trigeminal nerve, with that of nitroglycerin applied to the chin (innervated by the mandibular division), the posterolateral region of the neck (innervated by the second and third cervical roots), the lateral surface of the proximal third of the forearm (innervated by the sixth cervical root), and the medial surface of the upper-arm region (second dorsal root). One hundred patients suffering from migraine without aura were randomly divided into five equal groups. Each group received an application of 5 mg nitroglycerin in 2% ointment on a preselected body area for 2 hours. Frontotemporal nitroglycerin induced a significantly greater number of early onset migraine attacks with respect to the arm and forearm regions. In all cases, nitroglycerin applied to the frontotemporal region resulted in subsequent migraine, whereas there was a significant number of negative trials with nitroglycerin applied to the neck, arm, and forearm vs the frontotemporal area. It, therefore, appears that the trigeminal nerve endings in the affected frontotemporal region are particularly sensitive to the migraine-inducing effect of the nitrate. This suggests a peripheral neurogenic hypothesis of migraine genesis.

A number of pharmacological evidence supports the view that somatostatin (SS) may be importantly involved in the seizure susceptibility both in humans and in laboratory animals. In a previous report the Authors have provided the finding that a short-term carbamazepine (CBZ) administration is able to reduce SS-CSF-IR in epileptic patients. The present study has been carried out to investigate whether a long-term treatment with CBZ affects in a similar way SS-IR content in CSF from temporal lobe epileptics (CPS). The results confirm and expand previous evidence suggesting that CBZ lowering effect on CSF-SS-IR may be relevant to its anticonvulsivant action.