How to approach and take care of minor adolescents whose situations raise ethical dilemmas? a position paper of the European academy of pediatrics

In the care of adolescents, health care providers often face situations raising ethical concerns or dilemmas, such as refusal of a treatment or hospitalization, or request of confidentiality while engaging in risky behaviors or facing unplanned pregnancy. This position paper provides concrete avenues as how to assess the adolescent's capacity for autonomous decision making, e.g. the patient's competence in a specific situation, and how to elicit informed choice or consent. To do so, professionals need to be sensitized and trained as how to assess the cognitive and socio-psychological development of the young patient. Another challenge for the health professionals is to balance the needs to support patient's autonomy while offering secure guidance and protection if needed. To optimize such a process, they establish a climate of trust and empathy that will allow the patient to participate freely in the decision. In addition, especially when the decisions have potentially important consequences on the health and life, the professionals include, with the adolescent's permission, parents, caregivers or other significant adults, as well as they may request the opinion of other members of the health care team or expert colleagues such as ethicists

Phenotype Presentation and Molecular Diagnostic Yield in Non-5q Spinal Muscular Atrophy

BACKGROUND AND OBJECTIVES: Spinal muscular atrophy (SMA) is mainly caused by homozygous SMN1 gene deletions on 5q13. Non-5q SMA patients' series are lacking, and the diagnostic yield of next-generation sequencing (NGS) is largely unknown. The aim of this study was to describe the clinical and genetic landscape of non-5q SMA and evaluate the performance of neuropathy gene panels in these disorders. METHODS: Description of patients with non-5q SMA followed in the different neuromuscular reference centers in France as well as in London, United Kingdom. Patients without a genetic diagnosis had undergone at least a neuropathy or large neuromuscular gene panel. RESULTS: Seventy-one patients from 65 different families were included, mostly sporadic cases (60.6%). At presentation, 21 patients (29.6%) showed exclusive proximal weakness (P-SMA), 35 (49.3%) showed associated distal weakness (PD-SMA), and 15 (21.1%) a scapuloperoneal phenotype (SP-SMA). Thirty-two patients (45.1%) had a genetic diagnosis: BICD2 (n = 9), DYNC1H1 (n = 7), TRPV4 (n = 4), VCP, HSBP1, AR (n = 2), VRK1, DNAJB2, MORC2, ASAH1, HEXB, and unexpectedly, COL6A3 (n = 1). The genetic diagnostic yield was lowest in P-SMA (6/21, 28.6%) compared with PD-SMA (16/35, 45.7%) and SP-SMA (10/15, 66.7%). An earlier disease onset and a family history of the disease or consanguinity were independent predictors of a positive genetic diagnosis. Neuropathy gene panels were performed in 59 patients with a 32.2% diagnostic yield (19/59). In 13 additional patients, a genetic diagnosis was achieved through individual gene sequencing or an alternative neuromuscular NGS. DISCUSSION: Non-5q SMA is genetically heterogeneous, and neuropathy gene panels achieve a molecular diagnosis in one-third of the patients. The diagnostic yield can be increased by sequencing of other neuromuscular and neurometabolic genes. Nevertheless, there is an unmet need to cluster these patients to aid in the identification of new genes

European recommendations integrating genetic testing into multidisciplinary management of sudden cardiac death.

Sudden cardiac death (SCD) accounts for 10-20% of total mortality, i.e., one in five individuals will eventually die suddenly. Given the substantial genetic component of SCD in younger cases, postmortem genetic testing may be particularly useful in elucidating etiological factors in the cause of death in this subset. The identification of genes responsible for inherited cardiac diseases have led to the organization of cardiogenetic consultations in many countries worldwide. Expert recommendations are available, emphasizing the importance of genetic testing and appropriate information provision of affected individuals, as well as their relatives. However, the context of postmortem genetic testing raises some particular ethical, legal, and practical (including economic or financial) challenges. The Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), together with international experts, developed recommendations on management of SCD after a workshop sponsored by the Brocher Foundation and ESHG in November 2016. These recommendations have been endorsed by the ESHG Board, the European Council of Legal Medicine, the European Society of Cardiology working group on myocardial and pericardial diseases, the ERN GUARD-HEART, and the Association for European Cardiovascular Pathology. They emphasize the importance of increasing the proportion of both medical and medicolegal autopsies and educating the professionals. Multidisciplinary collaboration is of utmost importance. Public funding should be allocated to reach these goals and allow public health evaluation

The supplementation of female dogs with live yeast Saccharomyces cerevisiae var. boulardii CNCM I-1079 acts as gut stabilizer at whelping and modulates immunometabolic phenotype of the puppies

Time around parturition is a stressful period for both bitches and their puppies. The use of probiotics has been proposed, e.g., in pigs, to improve health status of sows, their reproductive performances and in turn, the health and performance of their progeny. The objective of the present study was to evaluate the impact, on both dams and puppies, of a supplementation of bitches with the live yeast Saccharomyces cerevisiae var. boulardii CNCM I-1079 (SB-1079) during the second part of the gestation and the lactation period. A total of 36 bitches of medium and large-sized breeds were enrolled. They were divided into two groups, one of which received 1.3 × 109 colony forming units of live yeast per day. At dam’s level, SB-1079 yeast shaped a different microbiota structure between the two groups just after whelping, impacted alpha diversity and some plasma metabolites related to energy metabolism. Regarding reproductive performances, SB-1079 improved gross energy of the colostrum (1.4 vs. 1.2 kcal of ME/g) as well as the concentration of protein in milk at Day 7 after parturition (10.4 vs. 7.6%). SB-1079 also reduced the odds of having low birth weight in the litter. At puppy’s level, a modulation of immunometabolic phenotype is suggested by the observation of increased growth rates during the early pediatric period (i.e., between 21 and 56 days of life, 225 vs. 190%) and a decrease of the IL-8:IL-10 ratio after vaccination against rabies (4.2 vs. 16.9). Our findings suggest that SB-1079 supplementation during gestation and lactation has the potential to enhance health of bitches and in turn health of puppies through maternal programming

Toenails as biomarker of exposure to essential trace metals: A review

Health problems associated with essential trace metals can result from both inadequate (i.e., low intake) and excessive exposures (i.e., from environmental and/or occupational source). Thus, measuring the exposure level is a real challenge for epidemiologists. Among non-invasive biomarkers that intend to measure long-term exposure to essential trace metals, the toenail is probably the biological matrix with the greatest potential. This systematic review collects the current evidence regarding the validity of toenail clippings as exposure biomarker for trace metals such as boron, cobalt, copper, iron, manganese, molybdenum, selenium, silicon, vanadium and zinc. Special attention was paid to the time-window of exposure reflected by the toenail, the intraindividual variability in exposure levels over time in this matrix, and the relationship of toenail with other biomarkers, personal characteristics and environmental sources. Our search identified 139 papers, with selenium and zinc being the most studied elements. The variability among studies suggests that toenail levels may reflect different degrees of exposure and probably correspond to exposures occurred 3–12 months before sampling (i.e., for manganese/selenium). Few studies assessed the reproducibility of results over time and, for samples obtained 1–6 years apart, the correlation coefficient were between 0.26 and 0.66. Trace metal levels in toenails did not correlate well with those in the blood and urine and showed low-moderate correlation with those in the hair and fingernails.This work was supported by FIS grants PI12/00150, PI17CIII/00034 & PI18/00287 (Instituto de Salud Carlos III, State Secretary of R + D + I and European Union (ERDF/ESF, "Investing in your future"))

Comparative genetic analysis: the utility of mouse genetic systems for studying human monogenic disease

One of the long-term goals of mutagenesis programs in the mouse has been to generate mutant lines to facilitate the functional study of every mammalian gene. With a combination of complementary genetic approaches and advances in technology, this aim is slowly becoming a reality. One of the most important features of this strategy is the ability to identify and compare a number of mutations in the same gene, an allelic series. With the advent of gene-driven screening of mutant archives, the search for a specific series of interest is now a practical option. This review focuses on the analysis of multiple mutations from chemical mutagenesis projects in a wide variety of genes and the valuable functional information that has been obtained from these studies. Although gene knockouts and transgenics will continue to be an important resource to ascertain gene function, with a significant proportion of human diseases caused by point mutations, identifying an allelic series is becoming an equally efficient route to generating clinically relevant and functionally important mouse models

J Med Genet

was previously implicated in periventricular nodular heterotopia (PVNH) in only five individuals and systematic clinical characterisation was not available. The aim of this study is to provide a comprehensive description of the phenotypic and genotypic spectrum of -related neurodevelopmental disorder. We collected detailed phenotypes of an international cohort of individuals (n=17) with variants assembled through the GeneMatcher platform. Missense variants were structurally modelled, and the impact of several were functionally validated. De novo variants (10 missense, 1 frameshift, 1 splice altering resulting in 9 residues insertion) in were identified among 17 unrelated individuals. Detailed phenotypes included intellectual disability (ID), microcephaly, seizures and PVNH. No specific facial characteristics were consistent across all cases, however microretrognathia was common. Various hearing and visual defects were recurrent, and interestingly, some inflammatory features were reported. MRI of the brain frequently showed abnormalities consistent with a neuronal migration disorder. We confirm the role of in an autosomal dominant syndrome with a phenotypic spectrum including severe ID, microcephaly, seizures and PVNH due to impaired neuronal migration

Etude des couplages plasma-spectrometrie de masse en vue d'applications analytiques: mise en oeuvre et especes observees

SIGLEINIST T 70788 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Circulations libertines dans le roman européen (1736-1803)

Cette thèse a pour objet l étude des influences du libertinage galant anglais et français sur la création allemande du dernier tiers du XVIIIe siècle. Le succès de diffusion outre-Rhin de quatre romans de séduction emblématiques du genre (Clarisse Harlove, Les Egarements du coeur et de l esprit, Le Paysan perverti et Les Liaisons dangereuses), plusieurs fois traduits et commentés par la critique contemporaine, légitime la recherche d échos au sein de la production allemande de la fin du siècle ; le recensement de preuves scientifiques d intérêt (aveux d influences, commentaires critiques ou intertextualité explicite) conduit à désigner six écrivains germaniques, lecteurs enthousiastes dont l oeuvre est entrée en résonance avec la tradition du libertinage galant : Christoph Martin Wieland, Sophie von La Roche, Wilhelm Heinse, Ludwig Tieck, Clemens Brentano et Jean Paul. Révélée par la confrontation des romans allemands avec les oeuvres sources , la reprise des motifs essentiels du libertinage galant, typologie des personnages, stratégies de conquête et épisodes-clés des intrigues , n est pas dissociable d une pratique du détournement ; l usage parodique de certains procédés narratifs traditionnels et les jeux d imitation viciée témoignent d une prise de distance dans laquelle s affirment à la fois l originalité des héritiers et la sensibilité plus germanique d une littérature en plein essor. Réorientant de manière significative certains principes fondamentaux de la quête galante, les dernières oeuvres allemandes infléchissent la doctrine libertine initiale et ouvrent sur de nouvelles interrogations existentielles, qui annoncent les figures désenchantées du XIXe siècle.This dissertation is a study of the influence of gallant libertine literature from England and France on German literary creation in the last three decades of the 18th century. The number of translations and critical commentaries which appeared at the time testifies to the successful impact in Germany of four novels of seduction, the very emblems of the genre, namely Clarissa Harlowe, Les Égarements du coeur et de l esprit, Le Paysan perverti and Les Liaisons dangereuses. It is therefore legitimate to search for echoes of those works in the German production of the late 18th century. The survey of scientific evidence of the attention paid to those novels (openly acknowledged influence, critical comments or explicit marks of intertextuality) results in the selection of six German writers, also enthusiastic readers of the books, whose works display a reflection of the tradition of gallant libertine literature, viz. Christoph Martin Wieland, Sophie von La Roche, Wilhelm Heinse, Ludwig Tieck, Clemens Brentano and Jean Paul. The confrontation between the German novels and the sources reveals the presence of the main motifs of gallant libertine literature: typology of characters, strategy of seduction and key phases in the plot. Yet it is inseparable from a systematic use of distortion. The parody of a series of narrative techniques and the recourse to perverted imitation bear witness to a process of distanciation in which both the originality of the literary heirs and the specifically German sensibility of a fast expanding literature assert themselves. By giving new directions to certain fundamental principles of the libertine quest, the latest German works in the corpus alter the initial libertine doctrine and pave the way for new areas of existential questions, thus foreshadowing the disillusioned artistic figures of the 19th century.PARIS3-BU (751052102) / SudocSudocFranceF