University of Erlangen-Nuremberg

About: University of Erlangen-Nuremberg is a education organization based out in Erlangen, Bayern, Germany. It is known for research contribution in the topics: Population & Immune system. The organization has 42405 authors who have published 85600 publications receiving 2663922 citations.

Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2010

Abstract: As in previous years, the consensus group to consider the use of biological agents in the treatment of rheumatic diseases met during the 13th Annual Workshop on Advances in Targeted Therapies in April, 2011. The group consisted of rheumatologists from a number of universities among the continents of Europe, North America, South America, Australia and Asia. Pharmaceutical industry support was obtained from a number of companies for the annual workshop itself, but these companies had no part in the decisions about the specific programme or about the academic participants at this conference. Representatives of the supporting sponsors participated in the initial working groups to supply factual information. The sponsors did not participate in the drafting of the consensus statement. This consensus was prepared from the perspective of the treating physician. In view of the new data for abatacept, B cell-specific agents, interleukin 1 (IL-1) antagonists, tocilizumab (TCZ) and tumour necrosis factor α blocking agents (TNF inhibitors), an update of the previous consensus statement is appropriate. To allow ease of updating, the 2010 (data from March 2009 to January 2010) updates are incorporated into the body of the article, while 2011 updates (February 2010–January 2011) are separated and highlighted. The consensus statement is annotated to document the credibility of the data supporting it as much as possible. This annotation is that of Shekelle et al and is described in appendix 1.1 We have modified the Shekelle annotation by designating all abstracts as ‘category D evidence’, whether they describe well-controlled trials or not, as details of the study were often not available in the abstracts. Further, the number of possible references has become so large that reviews are sometimes included; if they contain category A references, they will be referred to as category A evidence. The rheumatologists and bioscientists who attended …

The effectiveness of treatment for sexual offenders: A comprehensive meta-analysis

Abstract: The article reports a meta-analysis on controlled outcome evaluations of sexual offender treatment. From 2,039 documents published in five languages, 69 studies containing 80 independent comparisons between treated and untreated offenders fulfilled stepwise eligibility criteria (total N = 22,181). Despite a wide range of positive and negative effect sizes, the majority confirmed the benefits of treatment. Treated offenders showed 6 percentage points or 37% less sexual recidivism than controls. Effects for violent and general recidivism were in a similar range. Organic treatments (surgical castration and hormonal medication) showed larger effects than psychosocial interventions. However, this difference was partially confounded with methodological and offender variables. Among psychological programs, cognitive–behavioral approaches revealed the most robust effect. Nonbehavioral treatments did not demonstrate a significant impact. There was no outcome difference between randomized and other designs, however, group equivalence was associated with slightly larger effects. Various other moderators had a stronger impact on effect size (e.g., small sample size, quality of outcome reporting, program completion vs. dropout, age homogeneity, outpatient treatment, and authors’ affiliation with the program). More differentiated, high-quality evaluations are needed to clarify: What works for whom under which circumstances?

Structure-based discovery of opioid analgesics with reduced side effects

Abstract: Morphine is an alkaloid from the opium poppy used to treat pain. The potentially lethal side effects of morphine and related opioids-which include fatal respiratory depression-are thought to be mediated by μ-opioid-receptor (μOR) signalling through the β-arrestin pathway or by actions at other receptors. Conversely, G-protein μOR signalling is thought to confer analgesia. Here we computationally dock over 3 million molecules against the μOR structure and identify new scaffolds unrelated to known opioids. Structure-based optimization yields PZM21-a potent Gi activator with exceptional selectivity for μOR and minimal β-arrestin-2 recruitment. Unlike morphine, PZM21 is more efficacious for the affective component of analgesia versus the reflexive component and is devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses. PZM21 thus serves as both a probe to disentangle μOR signalling and a therapeutic lead that is devoid of many of the side effects of current opioids.

RAD51B in Familial Breast Cancer

Abstract: Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.