Autosomal dominant SCA5 and autosomal recessive infantile SCA are allelic conditions resulting from SPTBN2 mutations

Although many genes have been identified for the autosomal recessive cerebellar ataxias (ARCAs), several patients are unlinked to the respective loci, suggesting further genetic heterogeneity. We combined homozygosity mapping and exome sequencing in a consanguineous Egyptian family with congenital ARCA, mental retardation and pyramidal signs. A homozygous 5-bp deletion in SPTBN2, the gene whose in-frame mutations cause autosomal dominant spinocerebellar ataxia type 5, was shown to segregate with ataxia in the family. Our findings are compatible with the concept of truncating SPTBN2 mutations acting recessively, which is supported by disease expression in homozygous, but not heterozygous, knockout mice, ataxia in Beagle dogs with a homozygous frameshift mutation and, very recently, a homozygous SPTBN2 nonsense mutation underlying infantile ataxia and psychomotor delay in a human family. As there was no evidence for mutations in 23 additional consanguineous families, SPTBN2-related ARCA is probably rare.     

Exploiting PI3K/mTOR signaling to accelerate epithelial wound healing

The molecular circuitries controlling the process of skin wound healing have gained new significant insights in recent years. This knowledge is built on landmark studies on skin embryogenesis, maturation, and differentiation. Furthermore, the identification, characterization, and elucidation of the biological roles of adult skin epithelial stem cells and their influence in tissue homeostasis have provided the foundation for the overall understanding of the process of skin wound healing and tissue repair. Among numerous signaling pathways associated with epithelial functions, the PI3K/Akt/mTOR signaling route has gained substantial attention with the generation of animal models capable of dissecting individual components of the pathway, thereby providing a novel insight into the molecular framework underlying skin homeostasis and tissue regeneration. In this review, we focus on recent findings regarding the mechanisms involved in wound healing associated with the upregulation of the activity of the PI3K/Akt/mTOR circuitry. This review highlights critical findings on the molecular mechanisms controlling the activation of mTOR, a downstream component of the PI3K–PTEN pathway, which is directly involved in epithelial migration and proliferation. We discuss how this emerging information can be exploited for the development of novel pharmacological intervention strategies to accelerate the healing of critical size wounds.     

Comparative dynamics of four smoking withdrawal symptom scales

Aims To examine the association of person‐specific trajectories of withdrawal symptoms of urge‐to‐smoke, negative affect, physical symptoms and hunger during the first 7 days after smoking cessation with abstinence at end of treatment (EOT) and at 6 months. Design Hierarchical linear modeling (HLM) was used to model person‐specific trajectory parameters (level, slope, curvature and volatility) for withdrawal symptoms. Setting University‐based smoking cessation trials. Participants Treatment‐seeking smokers in clinical trials of transdermal nicotine versus nicotine spray (n = 514) and bupropion versus placebo (n = 421). Measurements Self‐reported withdrawal symptoms for 7 days after the planned quit date, and 7‐day point prevalence and continuous abstinence at EOT and 6 months. Findings In regressions that included trajectory parameters for one group of withdrawal symptoms, both urge‐to‐smoke and negative affect were predictive of abstinence while physical symptoms and hunger were generally not predictive. In stepwise regressions that included the complete set of trajectory parameters across withdrawal symptoms (for urge‐to‐smoke, negative affect, physical symptoms and hunger), with a single exception only the trajectory parameters for urge‐to‐smoke were predictive. Area under the receiver operator characteristic curve was 0.594 for covariates alone, and 0.670 for covariates plus urge‐to‐smoke trajectory parameters. Conclusions Among a number of different withdrawal symptoms (urge‐to‐smoke, negative affect, physical symptoms and hunger) urge‐to‐smoke trajectory parameters (level, slope and volatility) over the first 7 days of smoking cessation show the strongest prediction of both short‐ and long‐term relapse. Other withdrawal symptoms increase the predictive ability by negligible amounts.     

Factors Influencing Improvement of Trauma-Related Symptoms Among Somali Refugee Youth in Urban Kenya

Somali refugee youth present with a heightened risk for common mental disorders (CMDs), and yet few studies have discussed factors influencing mental health outcomes after psychosocial interventions. This study aimed to identify key factors that contribute to the improvement of CMD symptoms among Somali youth displaced in urban Kenya. Logistic regression analyses revealed that trauma exposure and emotional coping predict overall symptom improvement, pointing to a differential intervention effect on those with differing levels of religious belief and attitudes toward violence. This study provides insights into how psychosocial factors likely contribute to positive intervention outcomes in Somali refugee youth.

     

Semen quality of fertile US males in relation to their mothers' beef consumption during pregnancy

BACKGROUND To look at possible long-term risks from anabolic steroids and other xenobiotics in beef, we examined men's semen quality in relation to their mother's self-reported beef consumption during pregnancy. METHODS: The study was carried out in five US cities between 1999 and 2005. We used regression analyses to examine semen parameters in 387 partners of pregnant women in relation to the amount of beef their mothers reported eating while pregnant. Mothers' beef consumption was also analysed in relation to the son's history of previous subfertility. RESULTS Sperm concentration was inversely related to mothers' beef meals per week (P = 0.041). In sons of "high beef consumers" (>7 beef meals/week), sperm concentration was 24.3% lower (P = 0.014) and the proportion of men with sperm concentration below 20 x 10(6)/ml was three times higher (17.7 versus 5.7%, P = 0.002) than in men whose mothers ate less beef. A history of previous subfertility was also more frequent among sons of "high beef consumers" (P = 0.015). Sperm concentration was not significantly related to mother's consumption of other meat or to the man's consumption of any meat. CONCLUSIONS These data suggest that maternal beef consumption, and possibly xenobiotics in beef, may alter a man's testicular development in utero and adversely affect his reproductive capacity.