Early innate immune events induced by prolonged cold ischemia exacerbate allograft vasculopathy

Background  

Ischemia/reperfusion induced innate immune injury is inescapable in solid organ transplantation. Prolonged cold ischemia exacerbates the primary manifestation of late graft rejection, allograft vasculopathy (AV). The relationship between prolonged cold ischemia and late graft events is unclear and the subject of this study.     

Further genotype – phenotype correlations in neurofibromatosis 2

Selvanathan SK, Shenton A, Ferner R, Wallace AJ, Huson SM, Ramsden RT, Evans DG. Further genotype–phenotype correlations in neurofibromatosis 2. Neurofibromatosis 2 (NF2) is caused by mutations in the NF2 gene predisposing carriers to develop nervous system tumours. Different NF2 mutations result in either loss/reduced protein function or gain of protein function (abnormally behaving mutant allele i.e. truncated protein potentially causing dominant negative effect). We present a comparison between the clinical presentations of patients with mutations that are predicted to produce truncated protein (nonsense/frameshift mutations) to those that results in loss of protein expression (large deletions) to elucidate further genotype–phenotype correlations in NF2. Patients with nonsense/frameshift mutations have a younger age of diagnosis and a higher prevalence/proportion of meningiomas (p = 0.002, p = 0.014), spinal tumours (p = 0.004, p = 0.004) and non‐VIII cranial nerve tumours (p = 0.006, p = 0.003). We also found younger age of diagnosis of vestibular schwannomas (p = 0.007), higher mean numbers of cutaneous lesions (p = 0.003) and spinal tumours (p = 0.006) in these patients. With respect to NF2 symptoms, we found younger age of onset of hearing loss (p = 0.010), tinnitus (p = 0.002), paraesthesiae (p = 0.073), wasting and weakness (p = 0.001) and headaches (p = 0.049) in patients with nonsense/frameshift mutations. Our comparison shows, additional, new correlations between mutations in the NF2 gene and the NF2 disease phenotype, and this further confirms that nonsense/frameshift mutations are associated with more severe NF2 symptoms. Therefore patients with this class of NF2 mutation should be followed up closely.     

Gender specific trends in alcohol use: cross-cultural comparisons from 1998 to 2006 in 24 countries and regions

Objective:  

To examine trends in the prevalence of monthly alcohol use and lifetime drunkenness among 15 year olds in 20 European countries, the Russian Federation, Israel, the United States of America, and Canada.     

Dance is the new metal: adolescent music preferences and substance use across Europe

This study examined relationships between music preferences and substance use (tobacco, alcohol, cannabis) among 18,103 fifteen-year-olds from 10 European countries. In 2005-2006, across Europe, preferences for mainstream Pop (pop chart music) and Highbrow (classical music and jazz) were negatively associated with substance use, while preferences for Dance (house/trance and techno/hardhouse) were associated positively with substance use. In three countries, links were identified between liking Rock (rock, heavy metal punk/hardcore, and gothic) and substance use; associations between Urban (hip-hop and R&B) and substance use were mixed. No substantial gender differences emerged in these patterns, and controlling for relevant covariates did not attenuate the predictive value of substance use. The findings are consistent with the conclusion that music is a robust marker of adolescent substance use.     

Severe aplastic anemia: a prospective study of the effect of early marrow transplantation on acute mortality

A prospective randomized trial of therapy for severe aplastic anemia was designed to compare early bone marrow transplantation with conventional treatments. All patients with a sibling matched at the major histocompatibility region were transplanted. Transplantation was performed with 17-100 (median 33) days of original diagnosis. Conventional treatments included transfusion support with or without androgens. Twenty-four of 36 patients intered on the transplant arm are alive after 4-20 (median 9) mo with full marrow reconstitution. Only two are limited by chronic graft-versus-host disease. In contrast only 12 of 31 conventionally treated patients are alive. Six of these survivors have improved, five incompletely. The 19 nontransplant deaths have occurred within 1-11 (median 3) mo of diagnosis. Compared to nontransplant regimens, early transplantation more effectively restores normal marrow function and decreases the acute mortality of severe marrow aplasia (p = 0.006). Pending longer follow-up, early marrow transplantation appears to be the most effective available treatment for severe aplastic anemia.