Sexed up: theorizing the sexualization of culture

This paper reviews and examines emerging academic approaches to the study of ‘sexualized culture’; an examination made necessary by contemporary preoccupations with sexual values, practices and identities, the emergence of new forms of sexual experience and the apparent breakdown of rules, categories and regulations designed to keep the obscene at bay. The paper maps out some key themes and preoccupations in recent academic writing on sex and sexuality, especially those relating to the contemporary or emerging characteristics of sexual discourse. The key issues of pornographication and democratization, taste formations, postmodern sex and intimacy, and sexual citizenship are explored in detail. </p

Candidate gene resequencing in a large bicuspid aortic valve-associated thoracic aortic aneurysm cohort: SMAD6 as an important contributor

Bicuspid aortic valve (BAV) is the most common congenital heart defect. Although many BAV patients remain asymptomatic, at least 20% develop thoracic aortic aneurysm (TAA). Historically, BAV-related TAA was considered as a hemodynamic consequence of the valve defect. Multiple lines of evidence currently suggest that genetic determinants contribute to the pathogenesis of both BAV and TAA in affected individuals. Despite high heritability, only very few genes have been linked to BAV or BAV/TAA, such as NOTCH1, SMAD6, and MAT2A. Moreover, they only explain a minority of patients. Other candidate genes have been suggested based on the presence of BAV in knockout mouse models (e.g., GATA5, NOS3) or in syndromic (e.g., TGFBR1/2, TGFB2/3) or non-syndromic (e.g., ACTA2) TAA forms. We hypothesized that rare genetic variants in these genes may be enriched in patients presenting with both BAV and TAA. We performed targeted resequencing of 22 candidate genes using Haloplex target enrichment in a strictly defined BAV/TAA cohort (n = 441; BAV in addition to an aortic root or ascendens diameter = 4.0 cm in adults, or a Z-score = 3 in children) and in a collection of healthy controls with normal echocardiographic evaluation (n = 183). After additional burden analysis against the Exome Aggregation Consortium database, the strongest candidate susceptibility gene was SMAD6 (p = 0.002), with 2.5% (n = 11) of BAV/TAA patients harboring causal variants, including two nonsense, one in-frame deletion and two frameshift mutations. All six missense mutations were located in the functionally important MH1 and MH2 domains. In conclusion, we report a significant contribution of SMAD6 mutations to the etiology of the BAV/TAA phenotype

Long-term wheel running compromises diaphragm function but improves cardiac and plantarflexor function in the mdx mouse

Dystrophin-deficient muscles suffer from free radical injury, mitochondrial dysfunction, apoptosis, and inflammation, among other pathologies that contribute to muscle fiber injury and loss, leading to wheelchair confinement and death in the patient. For some time, it has been appreciated that endurance training has the potential to counter many of these contributing factors. Correspondingly, numerous investigations have shown improvements in limb muscle function following endurance training in mdx mice. However, the effect of long-term volitional wheel running on diaphragm and cardiac function is largely unknown. Our purpose was to determine the extent to which long-term endurance exercise affected dystrophic limb, diaphragm, and cardiac function. Diaphragm specific tension was reduced by 60% (P < 0.05) in mice that performed 1 yr of volitional wheel running compared with sedentary mdx mice. Dorsiflexor mass (extensor digitorum longus and tibialis anterior) and function (extensor digitorum longus) were not altered by endurance training. In mice that performed 1 yr of volitional wheel running, plantarflexor mass (soleus and gastrocnemius) was increased and soleus tetanic force was increased 36%, while specific tension was similar in wheel-running and sedentary groups. Cardiac mass was increased 15%, left ventricle chamber size was increased 20% (diastole) and 18% (systole), and stroke volume was increased twofold in wheel-running compared with sedentary mdx mice. These data suggest that the dystrophic heart may undergo positive exercise-induced remodeling and that limb muscle function is largely unaffected. Most importantly, however, as the diaphragm most closely recapitulates the human disease, these data raise the possibility of exercise-mediated injury in dystrophic skeletal muscle

Efficacy and tolerability of brivaracetam in patients with intellectual disability and epilepsy

Patients with intellectual disability (ID) are often excluded from clinical trials, and little is known about the best approach to treat their epilepsy. Brivaracetam (BRV) is a new antiepileptic drug (AED) for adjunctive treatment in patients with focal-onset seizures with or without secondary generalization. We analyzed the efficacy and tolerability of BRV in patients with ID and epilepsy who either had or had not previously received treatment with levetiracetam (LEV). Data on efficacy and tolerability were retrospectively collected. After the initial start of BRV in our tertiary epilepsy center, we analyzed medical records at 0, 3, 6 and 12 months of follow-up. 116 patients were included (mean age = 34.9 years, 44% female). All had complete data of 3-month follow-up, 76 of 6-month follow-up, and 39 patients of 1-year follow-up. Median starting dose of BRV was 50.0 mg/day and the mean number of concomitant AEDs was 2.6. Seizure reduction and no side effects were reported in more than half of all patients. The most reported side effects were somnolence, dizziness and aggression. Retention rates for BRV were 84.4%, 75.5% and 58.1% after 3, 6 and 12 months, respectively. Seizure reduction and side effects did not differ significantly between the groups with or without previous LEV treatment. We demonstrate that BRV is effective and well tolerated in patients with epilepsy and ID, even in those where previous LEV treatment failed