Examining gender differences in emerging tobacco use using the Adolescents' Need For Smoking Scale

Aims To investigate the influence of gender on emerging tobacco use by testing for gender‐based measurement invariance of the Adolescents' Need for Smoking Scale (ANSS) and examining gender differences on each dimension across increasing levels of amount smoked. Design Cross‐sectional survey. Setting Thirteen secondary schools located in British Columbia, Canada. Participants Data from 1425 youth who reported smoking at least once in the past month. Measurements Survey questions about demographic characteristics, tobacco smoking history and need for smoking. Findings The multi‐dimensional structure of the ANSS is equivalent in boys and girls and the ANSS questions are not gender‐biased. There were no significant gender differences in the levels of physical dependence across increasing levels of amount smoked. Girls scored higher than boys on levels of emotional dependence across increasing levels of life‐time cigarette exposure. Girls also had higher scores on the social dimension of the ANSS compared to boys among those who smoked 100 or more cigarettes. Conclusions Canadian girls score higher than boys on measures of emotional dependence and social attitudes associated with tobacco smoking.     

A novel splice-site variant in CDH23 in a patient with Usher syndrome type 1

ABSTRACT

Background: Gene editing has shown huge potential in correcting aberrant splicing and Cas13 has been identified as being particularly suitable for targeting RNA. It has therefore become increasingly important to highlight new splice site mutations that may be correctable, particularly in genes that are too large to be encoded by AAV vectors. About 20% of Usher Type 1 cases are caused by mutations in CDH23.

Purpose: To report a novel splice site mutation of CDH23 associated with Usher Type 1D.

Materials and Methods: Case report.

Results: A 35-year-old Caucasian female who is congenitally deaf with vestibular dysfunction presented with visual acuity of 6/12 in both eyes. Fundus examination revealed findings typical of retinitis pigmentosa with foveal preservation of photoreceptor layer. Next generation sequencing analysis revealed a novel homozygous variant, c.9319 + 1G>T in CDH23 consistent with the diagnosis of Usher Syndrome Type 1D. The c.9319 + 1G>T variant is predicted to affect splicing at the exon 65/intron 65 boundary, which highly likely leads to complete skipping of exon 65.

Conclusions: We describe a case of a typical Usher Syndrome Type 1D caused by a novel splice site variant in CDH23. Currently there are no treatments for CDH23 related retinal degeneration, partly because the cDNA size of 10kb is too large for AAV vector gene augmentation therapy. Alternative strategies include CRISPR-Cas9 adenine base editors and RNA editing with CRISPR-Cas13. Single-nucleotide editing represents a promising approach for targeting this variant in CDH23 to restore the wildtype splice donor site at this position.     

Molecular pathogenesis of H5 highly pathogenic avian influenza: the role of the haemagglutinin cleavage site motif

The emergence of H5N1 highly pathogenic avian influenza has caused a heavy socio‐economic burden through culling of poultry to minimise human and livestock infection. Although human infections with H5N1 have to date been limited, concerns for the pandemic potential of this zoonotic virus have been greatly intensified following experimental evidence of aerosol transmission of H5N1 viruses in a mammalian infection model. In this review, we discuss the dominance of the haemagglutinin cleavage site motif as a pathogenicity determinant, the host‐pathogen molecular interactions driving cleavage activation, reverse genetics manipulations and identification of residues key to haemagglutinin cleavage site functionality and the mechanisms of cell and tissue damage during H5N1 infection. We specifically focus on the disease in chickens, as it is in this species that high pathogenicity frequently evolves and from which transmission to the human population occurs. With >75% of emerging infectious diseases being of zoonotic origin, it is necessary to understand pathogenesis in the primary host to explain spillover events into the human population. © 2015 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd.     

Evaluation of brivaracetam: a new drug to treat epilepsy

Introduction: High prevalence of therapy-resistant epilepsy demands development of anticonvulsants with new mechanisms of action. Brivaracetam is an analogue of levetiracetam which binds to the synaptic vesicle protein 2A (SV2A) and decreases release of excitatory neurotransmitters.

Areas covered: Relevant published studies were searched for by predefined strategy in MEDLINE, EBSCO and SCINDEKS electronic databases. Brivaracetam is effective as adjunctive therapy for uncontrolled partial-onset seizures with or without secondary generalization in patients 16 years and older with epilepsy. It reduces baseline-adjusted focal seizure frequency per week from 7.3 to 12.8% over placebo. Adverse events rate in patients with brivaracetam is not higher than in patients with placebo.

Expert opinion: Brivaracetam is an important step forward in the treatment of therapy-resistant partial-onset seizures with or without secondary generalization. Its development was systematic and targeted. Due to its efficacy and excellent safety profile, it is likely that brivaracetam will be often prescribed. In future, efficacy and safety of brivaracetam should be tested in monotherapy settings and also in the first-line therapy of partial-onset seizures.     

The Landscape of microRNA Targeting in Prostate Cancer Defined by AGO-PAR-CLIP

MicroRNA (miRNA) deregulation in prostate cancer (PCa) contributes to PCa initiation and metastatic progression. To comprehensively define the cancer-associated changes in miRNA targeting and function in commonly studied models of PCa, we performed photoactivatable ribonucleoside-enhanced cross-linking immunoprecipitation of the Argonaute protein in a panel of PCa cell lines modeling different stages of PCa progression. Using this comprehensive catalogue of miRNA targets, we analyzed miRNA targeting on known drivers of PCa and examined tissue-specific and stage-specific pathway targeting by miRNAs. We found that androgen receptor is the most frequently targeted PCa oncogene and that miR-148a targets the largest number of known PCa drivers. Globally, tissue-specific and stage-specific changes in miRNA targeting are driven by homeostatic response to active oncogenic pathways. Our findings indicate that, even in advanced PCa, the miRNA pool adapts to regulate continuing alterations in the cancer genome to balance oncogenic molecular changes. These findings are important because they are the first to globally characterize miRNA changes in PCa and demonstrate how the miRNA target spectrum responds to staged tumorigenesis.     

Coronary myocardial bridge: an innocent bystander?

Myocardial bridge (MB) or tunneled coronary artery is an inborn abnormality, which implicates a systolic vessel compression with a persistent mid-late diastolic diameter reduction. Myocardial bridges are often observed during coronary angiography with an incidence of 0.5%-5.5%. The most involved coronary artery is the left anterior descending artery followed by the diagonal branches, the right coronary artery, and the left circumflex. The overall long-term prognosis is generally benign. However, several risk or precipitating factors (e.g., high heart rate, left ventricular hypertrophy, decreased peripheral vascular resistance) may trigger symptoms (most frequently angina). Herein, we describe two cases of symptomatic myocardial bridge, where medical treatment (i.e., inotropic negative drug) and coronary stenting were successfully utilized to treat this pathology. We also focus on the clinical presentation, and the diagnostic and therapeutic modalities to correctly manage this frequently observed congenital coronary abnormality, underlining the fact that in cases of typical angina symptoms without any significant coronary artery disease, MB should be considered as a possible differential diagnosis.     

Communication Capacity Building through Pharmacy Practice Simulation

Objective. To examine the effectiveness of simulated learning modules (SLMs) encompassing EXcellence in Cultural Experiential Learning and Leadership (EXCELL) core competencies in enhancing pharmacy students’ professional communication skills.Methods. Students completed three hours of preparatory lectures and eight hours of workshops comprising six SLMs themed around pharmacy practice and pharmacy placements. Each SLM comprised role-plays with actors, facilitation using EXCELL Social Interaction Maps (SIMs), and debriefing. Evaluations of SLMs included quantitative and qualitative survey responses collected before, during and after workshops, and after placements. Facilitators reflected on SLMs as a pedagogic modality.Results. Student feedback was positive about SLMs as an effective learning tool. The majority indicated areas of new learning and found SLMs enhanced their professional skills and confidence. Facilitator feedback was positive, and suggested SLM optimization strategies.Conclusion. Student and teaching team recommendations will inform future curriculum development including the optimization of SLMs in pharmacy education.