A 71-nucleotide deletion in the periaxin gene in an Italian patient with late-onset slowly progressive demyelinating CMT

Background: Charcot-Marie-Tooth disease (CMT) constitutes a group of heterogeneous hereditary motor and sensor neuropathies. Mutations in the periaxin (PRX) gene cause CMT4F with an autosomal recessive early-onset demyelinating neuropathy and are extremely rare in a non-Romani white population. Methods: We report on a 66-year-old Italian man presenting with slowly progressive and late-onset demyelinating CMT. The molecular analysis was performed using a custom panel containing 39 genes associated with the CMT phenotype. Results: The patient harbored a homozygous PRX 71-nucleotide deletion (c.3286_3356del71, I1096fsX17). Conclusions: This is the first report that describes such a genetic mutation in a population of non-Romani origin

Hacking for Good - Workshop Summary

At the 2019 Charleston Library Conference, five facilitators from a diversity of organizations led a pre-conference called Hacking for Good. The goal of the half-day pre-conference was to introduce participants to the “hacking mindset” beyond the traditionally understood technology-driven terminology. In this context, hacking refersred to an approach of identifying a challenge or set of challenges in their respective knowledge organizations and gathering a set of techniques or approaches to address and overcome those challenges. The pre-conference provided a highly interactive and supportive environment to consider all aspects of a workplace challenge related to workflows and personnel and determine the most effective tools to tackle that challenge

Gulf stream marine hydrokinetic energy off cape hatteras, north carolina

Multi-year measurements of current velocity, salinity, and temperature from fixed and vessel-mounted sensors quantify Gulf Stream (GS) marine hydrokinetic energy (MHK) resource variability and inform development off Cape Hatteras, NC. Vessel transects across the GS demonstrate a jet-like velocity structure with speeds exceeding 2.5 m/s at the surface, persistent horizontal shear throughout the jet, and strongest vertical shears within the cyclonic shear zone. Persistent equatorward flow at the base of the GS associated with the Deep Western Boundary Current (DWBC) produces a local maximum in vertical shear where stratification is weak and is postulated to be a site of strong turbulent mixing. Repeated transects at the same location demonstrate that the velocity structure depends upon whether the GS abuts the shelf slope or is offshore. Currents from a fixed acoustic Doppler current profiler (ADCP) deployed on the shoreward side of the GS exceed 1 m/s 64% of the time 40 m below the surface. The 3.75-year time series of currents from the ADCP mooring document large, roughly weekly variations in downstream and cross-stream speed (−0.5 to 2.5 m/s) and shear (± 0.05 s−1) over the entire water column due to passage of GS meanders and frontal eddies. Current reversals from the mean GS direction occur several times a month, and longer period variations in GS offshore position can result in reduced currents for weeks at a time. Unresolved small-scale shear is postulated to contribute significantly to turbulent mixing

The PsyCoLaus study: methodology and characteristics of the sample of a population-based survey on psychiatric disorders and their association with genetic and cardiovascular risk factors.

ABSTRACT: BACKGROUND: The Psychiatric arm of the population-based CoLaus study (PsyCoLaus) is designed to: 1) establish the prevalence of threshold and subthreshold psychiatric syndromes in the 35 to 66 year-old population of the city of Lausanne (Switzerland); 2) test the validity of postulated definitions for subthreshold mood and anxiety syndromes; 3) determine the associations between psychiatric disorders, personality traits and cardiovascular diseases (CVD), 4) identify genetic variants that can modify the risk for psychiatric disorders and determine whether genetic risk factors are shared between psychiatric disorders and CVD. This paper presents the method as well as somatic and sociodemographic characteristics of the sample. METHODS: All 35 to 66 year-old persons previously selected for the population-based CoLaus survey on risk factors for CVD were asked to participate in a substudy assessing psychiatric conditions. This investigation included the Diagnostic Interview for Genetic Studies to elicit diagnostic criteria for threshold disorders according to DSM-IV and algorithmically defined subthreshold syndromes. Complementary information was gathered on potential risk and protective factors for psychiatric disorders, migraine and on the morbidity of first-degree family members, whereas the collection of DNA and plasma samples was part of the original somatic study (CoLaus). RESULTS: A total of 3,691 individuals completed the psychiatric evaluation (67% participation). The gender distribution of the sample did not differ significantly from that of the general population in the same age range. Although the youngest 5-year band of the cohort was underrepresented and the oldest 5-year band overrepresented, participants of PsyCoLaus and individuals who refused to participate revealed comparable scores on the General Health Questionnaire, a self-rating instrument completed at the somatic exam. CONCLUSIONS: Despite limitations resulting from the relatively low participation in the context of a comprehensive and time-consuming investigation, the PsyCoLaus study should significantly contribute to the current understanding of psychiatric disorders and comorbid somatic conditions by: 1) establishing the clinical relevance of specific psychiatric syndromes below the DSM-IV threshold; 2) determining comorbidity between risk factors for CVD and psychiatric disorders; 3) assessing genetic variants associated with common psychiatric disorders and 4) identifying DNA markers shared between CVD and psychiatric disorders

Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking

Twin studies indicate that additive genetic effects explain most of the variance in nicotine dependence (ND), a construct emphasizing habitual heavy smoking despite adverse consequences, tolerance and withdrawal. To detect ND alleles, we assessed cigarettes per day (CPD) regularly smoked, in two European populations via whole genome association techniques. In these approximately 7500 persons, a common haplotype in the CHRNA3-CHRNA5 nicotinic receptor subunit gene cluster was associated with CPD (nominal P=6.9 x 10(-5)). In a third set of European populations (n= approximately 7500) which had been genotyped for approximately 6000 SNPs in approximately 2000 genes, an allele in the same haplotype was associated with CPD (nominal P=2.6 x 10(-6)). These results (in three independent populations of European origin, totaling approximately 15 000 individuals) suggest that a common haplotype in the CHRNA5/CHRNA3 gene cluster on chromosome 15 contains alleles, which predispose to ND

Drug Development for Rare Paediatric Epilepsies: Current State and Future Directions

Rare diseases provide a challenge in the evaluation of new therapies. However, orphan drug development is of increasing interest because of the legislation enabling facilitated support by regulatory agencies through scientific advice, and the protection of the molecules with orphan designation. In the landscape of the rare epilepsies, very few syndromes, namely Dravet syndrome, Lennox-Gastaut syndrome and West syndrome, have been subject to orphan drug development. Despite orphan designations for rare epilepsies having dramatically increased in the past 10 years, the number of approved drugs remains limited and restricted to a handful of epilepsy syndromes. In this paper, we describe the current state of orphan drug development for rare epilepsies. We identified a large number of compounds currently under investigation, but mostly in the same rare epilepsy syndromes as in the past. A rationale for further development in rare epilepsies could be based on the match between the drug mechanisms of action and the knowledge of the causative gene mutation or by evidence from animal models. In case of the absence of strong pathophysiological hypotheses, exploratory/basket clinical studies could be helpful to identify a subpopulation that may benefit from the new drug. We provide some suggestions for future improvements in orphan drug development such as promoting paediatric drug investigations, better evaluation of the incidence and the prevalence, together with the natural history data, and the development of new primary outcomes

MAO A VNTR polymorphism and amygdala volume in healthy subjects

The X-linked Monoamine Oxidase A (MAO A) gene presents a well known functional polymorphism consisting of a variable number of tandem repeats (VNTR) (long and short variants) previously associated with altered neural function of the amygdala. Using automatic subcortical segmentation (Freesurfer), we investigated whether amygdala volume could be influenced by this genotype. We studied 109 healthy subjects (age range 18-80 years; 59 male and 50 female), 74 carrying the MAO A High-activity allele and 35 the MAO A Low-activity allele. No significant effect of the MAO A polymorphism or interaction effect between polymorphism × gender was found on amygdalar volume. Thus, our findings suggest that the reported impact of the MAO A polymorphism on amygdala function is not coupled with consistent volumetric changes in healthy subjects. Future studies are needed to investigate whether the association between volume of the amygdala and the MAO A VNTR polymorphism is influenced by social/psychological variables, such as impulsivity, trauma history and cigarette smoking behaviour, not taken into account in this work

Embolization in Pediatric Patients: A Comprehensive Review of Indications, Procedures, and Clinical Outcomes

Embolization in pediatric patients encompasses a large spectrum of indications, ranging from the elective treatment of congenital diseases of the cardiovascular system to the urgent management of acute hemorrhagic conditions. In particular, the endovascular treatment of central and peripheral vascular malformations and hypervascular tumors represents a wide chapter for both congenital and acquired situations. Thanks to the progressive availability of low-profile endovascular devices and new embolic materials, the mini-invasive approach has gradually overtaken surgery. In this review, the main embolization procedures will be illustrated and discussed, with a focus on clinical indications and expected outcomes. The most recent mini-invasive techniques will be described, with hints on the cutting-edge devices and embolic materials