[Drugs: minors and harm reduction?] / Drogues : mineur-e-s et réduction des risques ?

The use of controlled substances (narcotics and psychotropic substances) poses increased risks for minors. However, minors are generally excluded from existing harm reduction services (e.g. drug consumption rooms, drug checking, exchange of consumption material). Based on public health considerations, the authors recommend the establishment of harm reduction services for minors.

La consommation de substances soumises à contrôle (stupéfiants et substances psychotropes) présente des risques accrus pour les mineur-e-s. Pourtant, ces derniers sont généralement exclus des offres existantes de réduction des risques et des méfaits (par exemple, locaux de consommation, drug checking, échange de matériel de consommation). Sur la base de considérations de santé publique, les auteurs recommandent la création de services de réduction des risques dédiés aux mineur-e-s.

Stress-Induced Premature Senescence Related to Oxidative Stress in the Developmental Programming of Nonalcoholic Fatty Liver Disease in a Rat Model of Intrauterine Growth Restriction.

Metabolic syndrome (MetS) refers to cardiometabolic risk factors, such as visceral obesity, dyslipidemia, hyperglycemia/insulin resistance, arterial hypertension and non-alcoholic fatty liver disease (NAFLD). Individuals born after intrauterine growth restriction (IUGR) are particularly at risk of developing metabolic/hepatic disorders later in life. Oxidative stress and cellular senescence have been associated with MetS and are observed in infants born following IUGR. However, whether these mechanisms could be particularly associated with the development of NAFLD in these individuals is still unknown. IUGR was induced in rats by a maternal low-protein diet during gestation versus. a control (CTRL) diet. In six-month-old offspring, we observed an increased visceral fat mass, glucose intolerance, and hepatic alterations (increased transaminase levels, triglyceride and neutral lipid deposit) in male rats with induced IUGR compared with the CTRL males; no differences were found in females. In IUGR male livers, we identified some markers of stress-induced premature senescence (SIPS) (lipofuscin deposit, increased protein expression of p21WAF, p16INK4a and Acp53, but decreased pRb/Rb ratio, foxo-1 and sirtuin-1 protein and mRNA expression) associated with oxidative stress (higher superoxide anion levels, DNA damages, decreased Cu/Zn SOD, increased catalase protein expression, increased nfe2 and decreased keap1 mRNA expression). Impaired lipogenesis pathways (decreased pAMPK/AMPK ratio, increased pAKT/AKT ratio, SREBP1 and PPARγ protein expression) were also observed in IUGR male livers. At birth, no differences were observed in liver histology, markers of SIPS and oxidative stress between CTRL and IUGR males. These data demonstrate that the livers of IUGR males at adulthood display SIPS and impaired liver structure and function related to oxidative stress and allow the identification of specific therapeutic strategies to limit or prevent adverse consequences of IUGR, particularly metabolic and hepatic disorders.

Endothelial Colony-Forming Cells Dysfunctions Are Associated with Arterial Hypertension in a Rat Model of Intrauterine Growth Restriction.

Infants born after intrauterine growth restriction (IUGR) are at risk of developing arterial hypertension at adulthood. The endothelium plays a major role in the pathogenesis of hypertension. Endothelial colony-forming cells (ECFCs), critical circulating components of the endothelium, are involved in vasculo-and angiogenesis and in endothelium repair. We previously described impaired functionality of ECFCs in cord blood of low-birth-weight newborns. However, whether early ECFC alterations persist thereafter and could be associated with hypertension in individuals born after IUGR remains unknown. A rat model of IUGR was induced by a maternal low-protein diet during gestation versus a control (CTRL) diet. In six-month-old offspring, only IUGR males have increased systolic blood pressure (tail-cuff plethysmography) and microvascular rarefaction (immunofluorescence). ECFCs isolated from bone marrow of IUGR versus CTRL males displayed a decreased proportion of CD31+ versus CD146+ staining on CD45- cells, CD34 expression (flow cytometry, immunofluorescence), reduced proliferation (BrdU incorporation), and an impaired capacity to form capillary-like structures (Matrigel test), associated with an impaired angiogenic profile (immunofluorescence). These dysfunctions were associated with oxidative stress (increased superoxide anion levels (fluorescent dye), decreased superoxide dismutase protein expression, increased DNA damage (immunofluorescence), and stress-induced premature senescence (SIPS; increased beta-galactosidase activity, increased p16INK4a, and decreased sirtuin-1 protein expression). This study demonstrated an impaired functionality of ECFCs at adulthood associated with arterial hypertension in individuals born after IUGR.

Endothelial Progenitor Cells Dysfunctions and Cardiometabolic Disorders: From Mechanisms to Therapeutic Approaches.

Metabolic syndrome (MetS) is a cluster of several disorders, such as hypertension, central obesity, dyslipidemia, hyperglycemia, insulin resistance and non-alcoholic fatty liver disease. Despite health policies based on the promotion of physical exercise, the reduction of calorie intake and the consumption of healthy food, there is still a global rise in the incidence and prevalence of MetS in the world. This phenomenon can partly be explained by the fact that adverse events in the perinatal period can increase the susceptibility to develop cardiometabolic diseases in adulthood. Individuals born after intrauterine growth restriction (IUGR) are particularly at risk of developing cardiovascular diseases (CVD) and metabolic disorders later in life. It has been shown that alterations in the structural and functional integrity of the endothelium can lead to the development of cardiometabolic diseases. The endothelial progenitor cells (EPCs) are circulating components of the endothelium playing a major role in vascular homeostasis. An association has been found between the maintenance of endothelial structure and function by EPCs and their ability to differentiate and repair damaged endothelial tissue. In this narrative review, we explore the alterations of EPCs observed in individuals with cardiometabolic disorders, describe some mechanisms related to such dysfunction and propose some therapeutical approaches to reverse the EPCs dysfunction.

Renal Programming by Transient Postnatal Overfeeding: The Role of Senescence Pathways.

BACKGROUND: Early nutrition influences the risk of chronic kidney diseases (CKDs) development in adulthood. Mechanisms underlying the early programming of altered renal function remain incompletely understood. This study aims at characterizing the role of cell senescence pathways in early programming of CKD after transient postnatal overfeeding. MATERIALS AND METHODS: Reduced litters of 3 mice pups and standard litters of 9 mice pups were obtained to induce overfed animals during lactation and control animals, respectively. Animals were sacrificed at 24 days (weaning) or at 7 months of life (adulthood). Body weight, blood pressure, kidney weight, and glomerular count were assessed in both groups. Senescence pathways were investigated using ß-Galactosidase staining and Western blotting of P16, P21, P53, P-Rb/Rb, and Sirtuin 1 (Sirt1) proteins. RESULTS: Early overfed animals had a higher body weight, a higher blood pressure at adulthood, and a higher glomerular number endowment compared to the control group. A higher ß-Galactosidase activity, a significant increase in P53 protein expression (p = 0.0045) and a significant decrease in P-Rb/Rb ratio (p = 0.02), were observed at weaning in animals who underwent early postnatal overfeeding. Protein expression of Sirt1, a protective factor against accelerated stress-induced senescence, was significantly decreased (p = 0.03) at weaning in early overfed animals. CONCLUSION: Early postnatal overfeeding by litter size reduction is associated with increased expression of factors involved in cellular senescence pathways, and decreased expression of Sirt 1 in the mouse kidney at weaning. These alterations may contribute to CKD programming after early postnatal overfeeding.

[Childhood food allergies: what if personalized medicine started here?] / Allergies alimentaires de l'enfant†: et si la médecine personnalisée commençait ici ?

Children's food allergies are a significant public health burden in industrialized countries. Their prevalence is also increasing in developing countries, reflecting the impact of modern globalized food that challenges humanity to adapt to unprecedented allergenic stress. The understanding of the multiple mechanisms involved in the emergence of these allergies has greatly improved over the past two decades. On the therapeutic level, the eviction regime has shown its limitations and risks in growing individuals. Personalized nutrition represents a promising field of investigation in therapeutic innovations.

Les allergies alimentaires de l'enfant sont un fardeau de santé publique important dans les pays industrialisés. Leur prévalence augmente également dans les pays en croissance, témoignant de l'impact d'une alimentation moderne globalisée qui met l'humanité au défi de s'adapter à un stress allergénique inédit. La compréhension des multiples mécanismes impliqués dans l'émergence de ces allergies a largement progressé depuis deux décennies. Sur le plan thérapeutique, le régime d'éviction a montré ses limites et ses risques chez des individus en croissance. La nutrition personnalisée représente un champ d'investigations, prometteur en innovations thérapeutiques.

Intra-uterine growth restriction induced by maternal low-protein diet causes long-term alterations of thymic structure and function in adult male rat offspring.

Early malnutrition, the first environmental cause of intra-uterine growth restriction, impairs development of the thymus. Alterations of the thymic structure and function are reported at young ages in murine and ovine models. However, descriptions of thymic consequences of fetal malnutrition at adulthood are scarce. The present study investigates thymic structure, protein expression and cell selection process observed at postnatal day 180 (PND180) in male offspring of rats exposed to maternal low-protein diet (mLPD) compared with control diet during gestation. The thymic index was lower in adult offspring exposed to mLPD (P < 0·05). The thymic cortico-medullar ratio was lower in adult offspring exposed to mLPD (P < 0·05). At PND180, the protein expression of the lymphotoxin ß receptor (P < 0·05), the autoimmune regulator (P < 0·05) and Forkhead Box P3 (FoxP3; P < 0·05) was all significantly lower in the mLPD group. The CD4+:CD8+ single-positive thymocyte subpopulation ratio and CD4+:CD8+ lymphocyte subpopulation ratio were increased in the mLPD group (P < 0·05). Among CD3+ lymphocytes, the proportions of CD4+CD8+ double-positive lymphocytes, CD31+ recent thymic emigrants and CD4+FoxP3+ lymphocytes were not significantly different between mLPD and control groups. These findings suggest mLPD during gestation induced long-lasting alterations in the development of thymic structure and thymic cell maturation and selection process in adult male rat offspring.

Calorie Restriction in Adulthood Reduces Hepatic Disorders Induced by Transient Postnatal Overfeeding in Mice.

Impaired early nutrition influences the risk of developing metabolic disorders in later life. We observed that transient postnatal overfeeding (OF) in mice induces long-term hepatic alterations, characterized by microsteatosis, fibrosis associated with oxidative stress (OS), and stress-induced premature senescence (SIPS). In this study, we investigated whether such changes can be reversed by moderate calorie restriction (CR). C57BL/6 male mice pups were maintained during lactation in litters adjusted to nine pups in the normal feeding (NF) group and three pups in the transient postnatal OF group. At six months of age, adult mice from the NF and OF groups were randomly assigned to an ad libitum diet or CR (daily energy supply reduced by 20%) for one month. In each group, at the age of seven months, analysis of liver structure, liver markers of OS (superoxide anion, antioxidant defenses), and SIPS (lipofuscin, p53, p21, p16, pRb/Rb, Acp53, sirtuin-1) were performed. CR in the OF group reduced microsteatosis, decreased levels of superoxide anion, and increased protein expression of catalase and superoxide dismutase. Moreover, CR decreased lipofuscin staining, p21, p53, Acp53, and p16 but increased pRb/Rb and sirtuin-1 protein expression. CR did not affect the NF group. These results suggest that CR reduces hepatic disorders induced by OF.

[When everything is frozen, start moving again: the FIT@CHUV program]. / Quand tout est gelé, se remettre à bouger†: programme FIT@CHUV.

The adolescent's painful functional disorders deserve management by a specialized interdisciplinary team. In recent years, intensive interdisciplinary physical therapy (IIPT) programs have developed in a hospital environment in Europe and around the world. While the short-term objective is often to restore trust between the patient and the therapists by relieving parents of the need to coordinate a network of multidisciplinary practitioners. These programs have proven to be effective in the medium and long term in improving the patient's clinical performance and for the benefits associated with restoring normal life for the family. Finally, these programs can have a positive impact in a cost-benefit approach when considering these often long and complex care arrangements.

Les troubles fonctionnels douloureux chroniques de l'adolescent méritent une prise en charge interdisciplinaire spécialisée. Depuis quelques années, des programmes de thérapie physique intensive interdisciplinaire (intensive interdisciplinary physical therapy, IIPT) se sont développés dans un environnement hospitalier en Europe et dans le monde. Si l'objectif à court terme est souvent de remettre les patients en mouvement, un autre objectif est de restaurer une confiance entre le patient et les professionnels de la santé en soulageant notamment les parents de la coordination d'un réseau de praticiens multidisciplinaires. Ces programmes ont montré leur efficacité à moyen et long termes sur l'amélioration clinique du patient et sur les bénéfices associés à la reprise d'une vie normale pour la famille. Enfin, ces programmes peuvent avoir un impact positif en termes de coût/bénéfice dans ces prises en charge souvent longues et complexes.

Offspring of mothers with hyperglycaemia in pregnancy: The short term and long-term impact. What is new?

The continuing rise in the global prevalence of diabetes and overweight or obesity has become a major burden for global health, as the pandemic is affecting both high and low-middle income countries (LMIC). At the same time, a similar pattern has been observed for all forms of hyperglycemia in pregnancy (HIP), diabetes during pregnancy and gestational diabetes. The offspring of mothers with HIP and/or overweight-obesity is receiving increasing attention as advances in early detection and treatment of HIP did not completely prevent macrosomia and its associated short-term perinatal disorders, whilst long term consequences are observed in the mother and in offspring as it reaches adulthood. This review discusses the current developments in the consequences of HIP in the offspring, with a particular focus on its long-term health at adulthood, and on intergenerational and transgenerational effects. HIP is emerging as one of the factors that can contribute, during the window of sensitivity to environmental cues constituted by the preconception, pregnancy, and early childhood, and as an amplifying factor linked to reproduction, to the current global epidemic of diabetes and non-communicable diseases (NCDs).

Perinatal Origins of Adult Disease.

Epidemiological and experimental studies have shown that the peri-conception period, pregnancy, and infancy are windows of particular sensibility to environmental clues which influence lifelong trajectories across health and disease. Nutrition, stress, and toxins induce epigenetic marks that control long-term gene expression patterns and can be transmitted transgenerationally. Chronic diseases of adulthood such as hypertension, diabetes, and obesity thus have early, developmental origins in the perinatal period. The early epigenome, in interaction with other actors such as the microbiome, add powerful layers of diversity to the biological predisposition generated by the genome. Such "programming" is a normal, adaptive component of development, including in normal pregnancies and births. However, perinatal disease, either maternal (such as pre-eclampsia, ges-tational diabetes, or inflammatory disease) or fetal, and neonatal diseases (such as intrauterine growth restriction and preterm birth) are major conditions of altered programming, translated into an increased risk for chronic disease in these patients when they reach adulthood. Early prevention, optimal perinatal nutrition, and specific follow-up measures are key factors in the early preservation of long-term health.

[Together we are stronger: management of complex functional disorders during adolescence]. / L'union fait la force :traitement des troubles fonctionnels complexes à l'adolescence.

Functional disorder during adolescence is a very complex problem too often limited to a psychological origin. Its pathogenesis remains unclear but it definitively associates individual and environmental factors. Recent data show anatomo-functional evidence of neural networks of the brain that is involved in pain and its psychological representation as well as the representation of pain in the body. We describe a holistic approach to manage functional disorders that include the family and promote adolescent centered care in order to reach a rapid and optimal rehabilitation.

Le trouble fonctionnel de l'adolescent est une pathologie complexe trop souvent réduite à un abord exclusivement psychologique. Sa genèse est encore insuffisamment comprise, mais elle associe certainement des facteurs individuels et environnementaux. Les données récentes montrent qu'il existe un support anatomo-fonctionnel au sein des réseaux neuronaux cérébraux impliqués dans la douleur et sa représentation psychique et corporelle. A l'instar des réseaux neuronaux, il s'agit souvent aussi d'une difficulté de travailler en réseau interdisciplinaire. Nous proposons ici une approche holistique de ces troubles, incluant les familles et plaçant l'adolescent au centre d'une prise en charge qui vise une réhabilitation rapide.

Transient postnatal overfeeding causes liver stress-induced premature senescence in adult mice.

Unbalanced nutrition early in life is increasingly recognized as an important factor in the development of chronic, non-communicable diseases at adulthood, including metabolic diseases. We aimed to determine whether transient postnatal overfeeding (OF) leads to liver stress-induced premature senescence (SIPS) of hepatocytes in association with liver structure and hepatic function alterations. Litters sizes of male C57BL/6 mice were adjusted to 9 pups (normal feeding, NF) or reduced to 3 pups during the lactation period to induce transient postnatal OF. Compared to the NF group, seven-month-old adult mice transiently overfed during the postnatal period were overweight and developed glucose intolerance and insulin resistance. Their livers showed microsteatosis and fibrosis, while hepatic insulin signaling and glucose transporter protein expressions were altered. Increased hepatic oxidative stress (OS) was observed, with increased superoxide anion production, glucose-6-phosphate dehydrogenase protein expression, oxidative DNA damage and decreased levels of antioxidant defense markers, such as superoxide dismutase and catalase proteins. Hepatocyte senescence was characterized by increased p21WAF, p53, Acp53, p16INK4a and decreased pRb/Rb and Sirtuin-1 (SIRT-1) protein expression levels. Transient postnatal OF induces liver OS at adulthood, associated with hepatocyte SIPS and alterations in liver structure and hepatic functions, which could be mediated by a SIRT-1 deficiency.

[Novelties 2016 in pediatrics]. / Pédiatrie.

Nutrition is central in pediatric care : essential for growth and development, it plays also a role in the prevention of many diseases.Even if breastfeeding is highly recommended, its implementation may be difficult in particular for premature and ill newborns. The creation of a specific unit for breastfeeding support in neonatology allows to help mothers willing to nurse and to improve the rate of breastfeeding for these vulnerable infants.Eating disorders represent an important challenge for patient care. Early detection and rapid management of anorexia is essential for the prognosis. This article describes the challenges and the practical process underlying the development of a practical guideline to manage children and adolescents hospitalized for anorexia.

La nutrition est un thème central en pédiatrie : essentielle pour la croissance et le développement de l'enfant, elle joue également un rôle dans la prévention de nombreuses maladies.Bien que fortement recommandée, la mise en place de l'allaitement peut être difficile en particulier chez les nouveau-nés prématurés ou malades. La création d'une unité de soutien à l'allaitement en néonatologie a permis d'offrir un soutien aux mères souhaitant allaiter et d'améliorer le taux de lactation. Les troubles du comportement alimentaire représentent un important challenge de prise en charge. Une détection et une prise en charge rapide de l'anorexie sont essentielles pour le pronostic. Cet article décrit les enjeux et le processus parcouru pour élaborer un guide de prise en charge des enfants et adolescent(e)s hospitalisé(e)s pour une anorexie.

Risk of Bacterial Meningitis in Children 6 to 11 Months of Age With a First Simple Febrile Seizure: A Retrospective, Cross-sectional, Observational Study.

OBJECTIVES: National and international guidelines are very heterogeneous about the necessity to perform a lumbar puncture (LP) in children under 12 months of age with a first simple febrile seizure. We estimated the risk of bacterial meningitis in children aged 6 to 11 months with a first simple febrile seizure. METHODS: This multicenter retrospective study was conducted in seven pediatric emergency departments (EDs) in the region of Paris, France. Visits of patients aged 6 to 11 months for a first simple febrile seizure from January 2007 to December 2011 were analyzed. Bacterial meningitis was sequentially sought for by 1) analyzing bacteriologic data at the time of the visit, 2) looking for data from a second visit to the hospital after the index visit, and 3) phone calling the child's parents to determine the symptom evolution after the index visit. Infants lost to this follow-up were searched for in a national bacterial meningitis database. RESULTS: From a total of 1,183,487 visits in the seven pediatric EDs, 116,503 were for children 6 to 11 months of age. From these, 205 visits were for a first simple febrile seizure. An LP was performed in 61 patients (29.8%). The outcome bacterial meningitis was ascertainable for 168 (82%) visits. No bacterial meningitis was found among these patients (95% confidence interval = 0% to 2.2%). None of the 37 infants lost to our follow-up were registered in the national database as having bacterial meningitis. CONCLUSIONS: Among children between 6 and 11 months of age with a first simple febrile seizure, the risk of bacterial meningitis is extremely low. These results should encourage national and international societies to either develop or endorse guidelines limiting routine LP in these infants and contribute to widely homogenized management practices.

Vaccine coverage of healthcare students in hospitals of the Paris region in 2009: the Studyvax survey.

INTRODUCTION: Healthcare students should comply with the same vaccination recommendations as employed healthcare professionals. Vaccination coverage data for healthcare students are lacking MATERIALS AND METHODS: This cross-sectional survey was carried out on medical, nursing and midwifery students in 15 hospitals of the Assistance Publique - Hôpitaux de Paris with a maternity ward. All midwifery students were surveyed, and a subset of medical and nursing students were selected from 10 hospitals by three-stage random sampling. Data were collected by face-to-face interviews and verified from health records. RESULTS: A total of 432 students were included in the study (178 medical, 147 nursing, 107 midwifery), of whom 376 (87%) had proof of vaccination. The confirmed coverage for compulsory vaccinations was 96.9% for the booster dose of diphtheria-tetanus-poliomyelitis vaccine, 93.6% for BCG and 91.8% for at least three doses of hepatitis B. The coverage for recommended vaccinations confirmed by a vaccine booklet was 44% for pertussis (booster at 11-13 or 16-18 years of age), and 79.3% and 49.6% for the first and second doses of measles, respectively. The rate for influenza vaccination was 39.6%, based on self-reported information. Of the 27 students without any history of varicella infection, six had been vaccinated. DISCUSSION: Vaccination coverage of healthcare students is high for compulsory vaccinations, but largely insufficient for recommended vaccinations. Increased awareness regarding the required vaccinations is necessary in this population, as well as stronger enforcement prior to initiating clinical work.