Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy

Mutations in the gene encoding dystrophin, a protein that maintains muscle integrity and function, cause Duchenne muscular dystrophy (DMD). The deltaE50-MD dog model of DMD harbors a mutation corresponding to a mutational “hotspot” in the human DMD gene. We used adeno-associated viruses to deliver CRISPR gene editing components to four dogs and examined dystrophin protein expression 6 weeks after intramuscular delivery (n = 2) or 8 weeks after systemic delivery (n = 2). After systemic delivery in skeletal muscle, dystrophin was restored to levels ranging from 3 to 90% of normal, depending on muscle type. In cardiac muscle, dystrophin levels in the dog receiving the highest dose reached 92% of normal. The treated dogs also showed improved muscle histology. These large-animal data support the concept that, with further development, gene editing approaches may prove clinically useful for the treatment of DMD

Structure-property and composition-property relationships for poly(ethylene terephthalate) surfaces modified by helium plasma-based ion implantation

The surfaces of untreated and helium plasma-based ion implantation (He PBII) treated poly(ethylene terephthalate) (PET) samples were characterised by reflectance colorimetry, contact angle studies and measurements of surface electrical resistance. The results were related to the structural and compositional data obtained by the authors earlier on parallel samples by XPS and Raman spectroscopy. Inverse correlations between lightness and ID/IG ratio and between chroma and ID/IG ratio were obtained, suggesting that the PBII-treated PET samples darken and their colourfulness decreases with the increase of the portion of aromatic sp2 carbon rings in the chemical structure of the modified layer. Direct correlation between water contact angle and the ID/IG ratio and inverse correlations between surface energy and ID/IG ratio and between dispersive component of surface energy and ID/IG ratio were found, reflecting that surface wettability, surface energy and its dispersive component decrease with the formation of surface structure, characterised again by enhanced portion of aromatic sp2 carbon rings. The surface electrical resistance decreased with the increase of the surface C-content determined by XPS and also with the increase of the surface concentration of conjugated double bonds, reflected by the increase of the pi-pi* shake-up satellite of the C 1s peak

Mindfulness and self-regulation: A comparison of longterm to short-term meditators

ABSTRACT: While Western researchers have mostly conceived of mindfulness as a way of regulating negative affect, Buddhist tradition and some recent studies suggest that mindfulness could be useful in regulating impulses as well. It was hypothesized that long-term meditators ($5 years of committed practice) would demonstrate greater self-regulatory skills as measured by the Self Regulation Questionnaire (SRQ) than short-term meditators. However, no significant differences were found between the groups. Experienced and novice meditators could have different motivations for practicing mindfulness, and this could have affected both groups' SRQ scores in various ways. Also, it is possible that if mindfulness does decrease impulsive behavior, it does so by mechanisms other than those proffered by the social cognitive view of self-regulation as represented by the SRQ

Nonmedical prescription psychiatric drug use and the darknet: A cryptomarket analysis

Nonmedical prescription psychiatric drug use (NMPDU) is an increasing global health problem, with recent concern focusing on darknet cryptomarkets as sources of procurement. There is a shortage of evidence regarding comparative worldwide NMPDU trends, due in part to data collection difficulties. This problem is particularly marked for non-opioid drugs, particularly those psychiatric drugs which act on the central nervous system (CNS) and have high misuse potential and are associated with high levels of dependency and fatal overdose. This paper therefore has two goals: 1) to report on the kinds of psychiatric prescription drugs available on cryptomarkets, and 2) to use this data to uncover temporal and geographical trends in sales of these products, potentially informing policy regarding NMPDU more generally. Method Digital trace data collected from 31 cryptomarkets in operation between September 2013 and July 2016 was analysed by country of origin descriptively and for trends in the sales for 7 psychiatric drug groupings, based on their main indication or intended use in psychiatric practice. Results Sedatives (such as diazepam and alprazolam) and CNS stimulants (mainly Adderall, modafinil and methylphenidate) had the greatest share of sales, but usage and trends varied by location. The UK has high and rising levels of sedative sales, whilst the USA has the greatest stimulant sales and increasing sedative rates. Sales of drugs used in the treatment of opioid dependency are also substantial in the USA. The picture is less clear in mainland Europe with high sales levels reported in unexpected Central and Northern European countries. There is evidence of a move towards the more potent sedative alprazolam – already implicated as a source of problematic NMPDU in the USA – in Australia and the UK. Sales of drugs such as antidepressants, antipsychotics, mood stabilisers and antidementia drugs – all drugs with limited abuse potential – were negligible, indicating minimal levels of online cryptomarket procurement for self-medicating mental health problems. Conclusion Predominantly, psychiatric drugs with potent sedative, stimulant or euphoriant effects are sold on cryptomarkets and this varies by country. With some caveats regarding the limitations of cryptomarket digital trace data taken into account, the study of trends of these products sold online over time may offer a novel and increasingly important window onto wider drug purchasing habits

Eight-month-old infants’ behavioural responses to peers’ emotions as related to the asymmetric frontal cortex activity

Infants are sensitive to and converge emotionally with peers’ distress. It is unclear whether these responses extend to positive affect and whether observing peer emotions motivates infants’ behaviors. This study investigates 8-month-olds’ asymmetric frontal EEG during peers’ cry and laughter, and its relation to approach and withdrawal behaviors. Participants observed videos of infant crying or laughing during two separate sessions. Frontal EEG alpha power was recorded during the first, while infants’ behaviors and emotional expressions were recorded during the second session. Facial and vocal expressions of affect suggest that infants converge emotionally with their peers’ distress, and, to a certain extent, with their happiness. At group level, the crying peer elicited right lateralized frontal activity. However, those infants with reduced right and increased left frontal activity in this situation, were more likely to approach their peer. Overall, 8-month-olds did not show asymmetric frontal activity in response to peer laughter. But, those infants who tended to look longer at their happy peer were more likely to respond with left lateralized frontal activity. The link between variations in left frontal activity and simple approach behaviors indicates the presence of a motivational dimension to infants’ responses to distressed peers

Partners for the optimal organisation of the healthcare continuum for high users of health and social services: protocol of a developmental evaluation case study design

Contains fulltext : 138964.pdf (publisher's version ) (Open Access)INTRODUCTION: Case management allows us to respond to the complex needs of a vulnerable clientele through a structured approach that promotes enhanced interaction between partners. Syntheses on the subject converge towards a need for a better description of the relationships between programmes and their local context, as well as the characteristics of the clienteles and programmes that contribute to positive impacts. The purpose of this project is thus to describe and evaluate the case management programmes of four health and social services centres in the Saguenay-Lac- Saint-Jean region of Quebec, Canada, in order to inform their improvement while creating knowledge on case management that can be useful in other contexts. METHODS AND ANALYSIS: This research relies on a multiple embedded case study design based on a developmental evaluation approach. We will work with the case management programme for high users of hospital services of each centre. Three different units of analysis will be interwoven to obtain an in-depth understanding of each case, that is: (1) health and social services centre and local services network, (2) case management programme and (3) patients who are high users of services. Two strategies for programme evaluation (logic models and implementation analysis) will guide the mixed data collection based on qualitative and quantitative methods. This data collection will rely on: (1) individual interviews and focus groups; (2) participant observation; (3) document analysis; (4) clinical and administrative data and (5) questionnaires. Description and comparison of cases, and integration of qualitative and quantitative data will be used to guide the data analysis. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Research Boards of the four health and social services centres (HSSCs) involved. Findings will be disseminated by publications in peer-reviewed journals, conferences, and policy and practice partners in local and national government

Correction of Three Prominent Mutations in Mouse and Human Models of Duchenne Muscular Dystrophy by Single-Cut Genome Editing

Olson and colleagues generated new mouse and human iPSC models of Duchenne muscular dystrophy (DMD), harboring common exon deletions found in DMD patients. A CRISPR-Cas9 single-cut genome editing approach enabled exon skipping and exon reframing to efficiently restore dystrophin expression in the DMD models