Diagnostic value of exome and whole genome sequencing in craniosynostosis

Background Craniosynostosis, the premature fusion of one or more cranial sutures, occurs in ~1 in 2250 births, either in isolation or as part of a syndrome. Mutations in at least 57 genes have been associated with craniosynostosis, but only a minority of these are included in routine laboratory genetic testing. Methods We used exome or whole genome sequencing to seek a genetic cause in a cohort of 40 subjects with craniosynostosis, selected by clinical or molecular geneticists as being high-priority cases, and in whom prior clinically driven genetic testing had been negative. Results We identified likely associated mutations in 15 patients (37.5%), involving 14 different genes. All genes were mutated in single families, except for IL11RA (two families). We classified the other positive diagnoses as follows: commonly mutated craniosynostosis genes with atypical presentation (EFNB1, TWIST1); other core craniosynostosis genes (CDC45, MSX2, ZIC1); genes for which mutations are only rarely associated with craniosynostosis (FBN1, HUWE1, KRAS, STAT3); and known disease genes for which a causal relationship with craniosynostosis is currently unknown (AHDC1, NTRK2). In two further families, likely novel disease genes are currently undergoing functional validation. In 5 of the 15 positive cases, the (previously unanticipated) molecular diagnosis had immediate, actionable consequences for either genetic or medical management (mutations in EFNB1, FBN1, KRAS, NTRK2, STAT3). Conclusions This substantial genetic heterogeneity, and the multiple actionable mutations identified, emphasises the benefits of exome/whole genome sequencing to identify causal mutations in craniosynostosis cases for which routine clinical testing has yielded negative results

Molecular Adsorbents Recirculating System (MARS): evidence and management pitfalls

published_or_final_versio

Assessment and litigation of ocular injuries by less-lethal weapons.

The main cause of serious ophthalmological injuries, includingviolent eye amputations in the context of so-called less lethalweapons, is the use of blunt objects, such as batons or extendablesticks and the use of kinetic energy projectiles (rubber bullets,pellets, foam projectiles or others). Such injuries in the contextof population control have been considered to constitute cruel,inhuman or degrading treatment or even torture when they arecarried out, intentionally or unintentionally, by State officials(or with their acquiescence or protection) and involve any of thepurposes contemplated in the Convention against Torture. Dueto their special characteristics, they constitute rights violationsthat entail unique difficulties and complexity from both a legaland forensic point of view. This paper addresses some of thesedifficulties with practical legal and forensic recommendations.It is structured in two parts: First, legal, where we considerlegal difficulties and provide suggestions on elements for obtainingevidence are given. Second, medico-psychological andforensic where we review the elements to be considered in theinterview, the medical and ophthalmological evaluation, andthe psychometric, psychological and psychiatric evaluation

The faunal drugstore: Animal-based remedies used in traditional medicines in Latin America

Zootherapy is the treatment of human ailments with remedies made from animals and their products. Despite its prevalence in traditional medical practices worldwide, research on this phenomenon has often been neglected in comparison to medicinal plant research. This review discusses some related aspects of the use of animal-based remedies in Latin America, identifies those species used as folk remedies, and discusses the implications of zootherapy for public health and biological conservation. The review of literature revealed that at least 584 animal species, distributed in 13 taxonomic categories, have been used in traditional medicine in region. The number of medicinal species catalogued was quite expansive and demonstrates the importance of zootherapy as an alternative mode of therapy in Latin America. Nevertheless, this number is certainly underestimated since the number of studies on the theme are very limited. Animals provide the raw materials for remedies prescribed clinically and are also used in the form of amulets and charms in magic-religious rituals and ceremonies. Zootherapeutic resources were used to treat different diseases. The medicinal fauna is largely based on wild animals, including some endangered species. Besides being influenced by cultural aspects, the relations between humans and biodiversity in the form of zootherapeutic practices are conditioned by the social and economic relations between humans themselves. Further ethnopharmacological studies are necessary to increase our understanding of the links between traditional uses of faunistic resources and conservation biology, public health policies, sustainable management of natural resources and bio-prospecting

Light environment - A. Visible light. B. Ultraviolet light

Visible and ultraviolet light environment as related to human performance and safety during space mission

Assessment and litigation of ocular injuries by less-lethal weapons.

The main cause of serious ophthalmological injuries, including violent eye amputations in the context of so-called less lethal weapons, is the use of blunt objects, such as batons or extendable sticks and the use of kinetic energy projectiles (rubber bullets, pellets, foam projectiles or others). Such injuries in the context of population control have been considered to constitute cruel, inhuman or degrading treatment or even torture when they are carried out, intentionally or unintentionally, by State officials (or with their acquiescence or protection) and involve any of the purposes contemplated in the Convention against Torture. Due to their special characteristics, they constitute rights violations that entail unique difficulties and complexity from both a legal and forensic point of view. This paper addresses some of these difficulties with practical legal and forensic recommendations. It is structured in two parts: First, legal, where we consider legal difficulties and provide suggestions on elements for obtaining evidence are given. Second, medico-psychological and forensic where we review the elements to be considered in the interview, the medical and ophthalmological evaluation, and the psychometric, psychological and psychiatric evaluation

Diagnostic value of exome and whole genome sequencing in craniosynostosis

BACKGROUND: Craniosynostosis, the premature fusion of one or more cranial sutures, occurs in ∼1 in 2250 births, either in isolation or as part of a syndrome. Mutations in at least 57 genes have been associated with craniosynostosis, but only a minority of these are included in routine laboratory genetic testing. METHODS: We used exome or whole genome sequencing to seek a genetic cause in a cohort of 40 subjects with craniosynostosis, selected by clinical or molecular geneticists as being high-priority cases, and in whom prior clinically driven genetic testing had been negative. RESULTS: We identified likely associated mutations in 15 patients (37.5%), involving 14 different genes. All genes were mutated in single families, except for IL11RA (two families). We classified the other positive diagnoses as follows: commonly mutated craniosynostosis genes with atypical presentation (EFNB1, TWIST1); other core craniosynostosis genes (CDC45, MSX2, ZIC1); genes for which mutations are only rarely associated with craniosynostosis (FBN1, HUWE1, KRAS, STAT3); and known disease genes for which a causal relationship with craniosynostosis is currently unknown (AHDC1, NTRK2). In two further families, likely novel disease genes are currently undergoing functional validation. In 5 of the 15 positive cases, the (previously unanticipated) molecular diagnosis had immediate, actionable consequences for either genetic or medical management (mutations in EFNB1, FBN1, KRAS, NTRK2, STAT3). CONCLUSIONS: This substantial genetic heterogeneity, and the multiple actionable mutations identified, emphasises the benefits of exome/whole genome sequencing to identify causal mutations in craniosynostosis cases for which routine clinical testing has yielded negative results