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Background Male pattern baldness (androgenetic alopecia, AGA) is a highly heritable trait and the most common form of hair loss in humans. Eight genome-wide significant risk loci for AGA have been identified. Objectives To determine whether a polygenic component contributes to the genetic risk for AGA. Methods This study used a German case-control sample for AGA, which comprised 581 severely affected patients and 617 controls, to determine the contribution of polygenic variance to AGA risk. The sample was divided evenly into discovery and test samples. An additive polygenic risk score was calculated from risk alleles with increasingly liberal P-values in the discovery dataset, which was then used to test for the enrichment of AGA risk score alleles in the independent test samples. Results The polygenic score analysis provided significant evidence for a polygenic contribution to AGA where the amount of variance explained was 1·4-4·5%. Conclusion This study provides evidence for the specific contribution of a polygenic component to the overall heritable risk for AGA. To some degree, the polygenic architecture of AGA might reflect the complexity of the biological pathways involved. Further analyses and strategies that complement conventional genome-wide association studies are needed to identify these factors. These may include pathway-based analyses, the analysis of functional candidate genes and tests for epistatic effects with known loci. [ABSTRACT FROM AUTHOR]

For patients with severe skin wounds, topically applied morphine is an option to induce efficient analgesia due to the presence of opioid receptors in the skin. However, for topical administration it is important to know whether the substance is biotransformed in the skin as this can eventually reduce the concentration of the active agent considerably. We use skin microsomes to elucidate the impact of skin metabolism on the activity of topically applied morphine. We are able to demonstrate that morphine is only glucuronidated in traces, indicating that the biotransformation in the skin can be neglected when morphine is applied topically. Hence, there is no need to take biotransformation into account when setting up the treatment regimen. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Summary Background Male-pattern baldness (androgenetic alopecia, AGA) is the most common form of hair loss among humans. Research has shown that it is caused by genetic factors. Numerous studies have unequivocally identified two major genetic risk loci for AGA: the X-chromosomal AR/ EDA2R locus, and the PAX1/ FOXA2 locus on chromosome 20. Objectives To identify further candidate genes for AGA, and thus gain further insights into this phenotype. Methods A German sample of 581 severely affected cases and 617 controls was used to perform a genome-wide association study. The identified associated locus was further analysed by fine-mapping, and then independently replicated in an Australian sample. Expression and pathway analyses were performed to characterize the susceptibility gene identified. Results The most significant association signal was obtained for rs756853 ( P = 1·64 × 10−7), which is located intronically in the histone deacetylase 9 ( HDAC9) gene. Fine-mapping and a family-based analysis revealed that rs756853 and the 6-kb distal rs2249817 were the most highly associated single nucleotide polymorphisms. The association finding was replicated in an independent Australian sample, when the analysis was restricted to severely affected cases and unaffected controls ( P = 0·026). Analysis of rs2249817 in a combined sample of severely affected German and Australian cases and unaffected controls revealed a strong association signal ( P = 9·09 × 10−8). Tissue expression studies demonstrated HDAC9 expression in various tissues, including tissues of relevance to AGA. No strong genotypic effects were observed in genotype-specific expression or splice studies. Pathway analyses supported the hypothesis that HDAC9 plays a functional role in AGA via interaction with the AR gene. Conclusions The present study suggests that HDAC9 is the third AGA susceptibility gene. [ABSTRACT FROM AUTHOR]

The article presents a study on the use of a global gene expression approach to distinguish expressed genes in nonbalding vs. balding scalp from men with androgenetic alopecia (AGA). The study showed increased levels of enzymatic product prostaglandin D2 (PGD2) and prostaglandin D2 synthase (PTGDS) in balding vs. nonbalding scalp. The study suggests an inhibitory impact of increased PTGDS and PGD2 on hair growth by premature catagen induction.

Many patients with olfactory dysfunction not only experience quantitative reduction of olfactory function, but also suffer from distorted olfactory sensations. This qualitative dysfunction is referred to as parosmia (also called “troposmia”) or phantosmia, with the major difference that distorted olfactory sensations are experienced in the presence or absence of an odor, respectively. Our clinical observations corroborate the literature in terms of a general underestimation of the incidence of olfactory distortions. Based on selected cases we try to show that olfactory distortions exhibit a large variance in their clinical appearance. Further, emphasis is placed on the fact that only a detailed and directed history of the patient can provide cues to the correct diagnosis. [ABSTRACT FROM AUTHOR]

The adhesion and failure mechanism at well-designed titanium-PEEK interfaces within Ti-CF/PEEK laminates are investigated by superposed mode I- and mode II-loading before and after hydrothermal aging. The laser-induced columnar structured oxide layer enhances the adhesion at the Titanium-PEEK interface. PEEK-Polymer that is locked mechanically in the capillary gaps of the columnar oxide structure are stretched and stiffed in the case of loading resulting in good adhesion. The adhesion at the oxide structure reduces by the influence of hydrothermal aging. Basically, the failure mechanism is not changed. Thus, the columnar oxide structure leads to enhanced humidity resistance of the adhesion between titanium and PEEK. The PEEK-Polymer is also locked in the undercuts between the depressions and rims of the laser-induced dot-like surface structure resulting in adhesion. The adhesion at the dot-like structured surface is nearly completely reduced by the influence of hydrothermal aging. The failure mechanism is changed from ductile failure within the PEEK-Polymer to party disrupted rims and melt spatter. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the study that demonstrates fine mapping of androgen receptor (AR) and ectodysplasin A2 receptor (EDA2R) locus among patients with androgenetic alopecia (AGA).