tions in TEWL measurements of tape-stripped adult back skin (Fig. S3). ConclusionsIn summary, our results indicate that Calm4 is dispensable for epidermal barrier formation, skin homoeostasis, keratinocyte migration and wound healing. Calm4 À/À mice displayed no overt phenotypes and accordingly, their skin transcriptomes were very similar to wild-type controls. While we found no evidence of functional compensation by the highly homologous Calm5 or other Calmodulin isoforms, it is possible that other Ca 2+-binding proteins can functionally compensate for Calm4 in epidermal barrier formation and/or restoration, for example Calml3, which is highly expressed during the wound re-epithelialization stage in human skin (4). We also cannot rule out that Calm4 plays a nonredundant role in certain specialized responses to epidermal challenges that we did not address, for example pathogen exposure. However, the lack of an in vivo phenotype in mice genetically null for a small epidermal Ca 2+ -binding protein is not unique to Calm4. S100A9 À/À mice also appear grossly normal, even in several in vivo inflammatory assays, where S100A9 is normally expressed at high levels by both keratinocytes and skin-infiltrating leucocytes (9). Our findings therefore reinforce the notion that the establishment, maintenance and repair of the epidermal barrier are tightly regulated events involving a large and sometimes redundant assortment of signalling molecules. AcknowledgementsThe authors thank Dr. Gustavo Gutierrez-Cruz and Dr. Hong-Wei Sun for help with the RNAseq experiments, Kimberly Hilsen for assistance with mouse breeding and Dr. Mary Ann Stepp for input relating to the wound healing studies. This research was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH (ZIA AR041124-15 to M.I. Morasso). Author contributionsJCL, AK and MIM designed the study; JCL and AK performed the research; JCL, AK, PB and MIM analyzed the data; JCL and MIM wrote the paper. Conflict of interestThe authors declare no conflict of interest. Supporting InformationAdditional supporting data may be found in the supplementary information of this article. Figure S1. Fig. 1g). Figure S2. Validation of RNAseq results by qPCR. Data is represented as the average of three biological replicates normalized to actin. Figure S3. Tape stripping of adult back skin leads to an increase in TEWL, but no significant differences between wild-type and Calm4 À/À . Appendix S1. Experimental design. 57Letter to the Editor result shows that leptin level is differentially expressed during hair cycle, the lowest in early anagen phase, upregulated in late anagen phase and the highest in the telogen phase. On the other hand, leptin receptor is detected in keratin 15-positive hair bulge epithelium of both anagen-and telogen-phase hair follicles of mice pelage and vibrissa hair, and hair from human scalp. Leptin contributes to adipocyte-mediated growth inhibition of anagenphase vibrissa hair as demonstrate...

In addition to genetics and androgens, novel factors could play a role in androgenetic alopecia (AGA). This study aims to investigate the association between plasma leptin level with the risk and severity of AGA in men. Forty-eight subjects were enrolled including 29 AGA and 19 non-AGA subjects. The plasma leptin level was significantly higher in AGA subjects, compared to non-AGA subjects (4.45 vs 2.76 ng/mL, P<.05).A higher plasma leptin levels were positively correlated with the risk of developing AGA in multivariate logistic analysis (odds ratio=2.77, P<.05). Leptin from the circulation might impact the development of AGA. | BACKGROUNDAndrogenetic alopecia (AGA) is regarded as an androgen-mediated process that occurs in genetically susceptible patients. However, factors other than androgens are believed to be involved in the pathogenesis of AGA because anti-androgen treatment does not completely reverse miniaturization. [1] Our previous study in men with AGA revealed that obesity is associated with a higher severity of hair loss.[2] Those findings suggested that obesity-associated metabolic changes could be a modulator for the progression of AGA. Leptin is a major adipocyte-derived factor, and its plasma level is commonly up-regulated in obese subjects due to the increased adipose tissue and the concomitant development of central leptin resistance. [3] Leptin has been reported to modulate the growth of hair follicles. [4,5] | QUESTIONS ADDRESSEDWe hypothesize that systemic leptin levels might modulate the growth of hair follicles and subsequently impact the development and severity of hair diseases. Therefore, we conducted the current study to investigate the association between plasma leptin levels with the risk and severity of AGA in men. | EXPERIMENTAL DESIGNMale subjects who were diagnosed as male pattern AGA or healthy volunteers with no history of AGA (non-AGA) at the age of 20-50 years were included in this study. The details of exclusion criteria and assessment of AGA are summarized in Data S1. The blood samples were taken from all subjects in the early morning after 8 hours of fasting.Enzyme-linked immunoassay kits were then used for the quantification of plasma levels of leptin, adiponectin, testosterone, insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1). | RESULTSA total of 48 subjects were enrolled in this study including 29 subjects with AGA and 19 non-AGA control subjects. The mean age of AGA subjects was 28.8 years and non-AGA subjects 34.1 years. Among the AGA subjects, 17 of them were diagnosed as mild severity (grade 2-3) and 12 subjects advanced severity (grade 4-6).BMI was not significantly different between AGA and non-AGA subjects ( Figure 1A) and was not correlated with the onset of AGA Abbreviations: AGA, androgenetic alopecia; BMI, body mass index; IGF, insulin growth factor;OR, odds ratio; TGF, transforming growth factor.F I G U R E 1 BMI and plasma leptin level in AGA group (AGA+) vs non-AGA group (AGA-) and mild AGA group vs severe AGA group...

This study explored and compared the effects of depression and antidepressants on sexual dysfunction in men with diabetes mellitus (DM). Patients and Methods: Patients older than 18 years who had been newly diagnosed with DM (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 250) between 1999 and 2010 were identified from Taiwan's National Health Insurance Research Database and were followed up until 2013. Patients with preexisting depression or sexual dysfunction were excluded. A total of 636,210 patients with DM were enrolled. These patients were divided into two groups: DM with comorbid depression and a matched cohort without depression. The groups were followed up until the end of 2010 for the first diagnosis of sexual dysfunction (ICD-9-CM codes 302.70, 302.71, 302.72, 302.74, 302.75, 302.76, 302.79, 607.84, and V417). A Cox proportional hazard model and a Cox regression model with time-dependent covariates were applied. Results: Patients with DM and depression had a higher risk of sexual dysfunction than those with DM without depression (hazard ratio [HR] = 1.44; 95% confidence interval [CI], 1.33-1.55). The risk of sexual dysfunction was lower in the subgroup who used antidepressants (per 28 cumulative defined daily doses [cDDDs]), HR = 0.96; 95% CI, 0.94-0.97). A significantly lower incidence of sexual dysfunction was also associated with the use of selective serotonin reuptake inhibitors (SSRIs, per 28 cDDD). The adjusted HR was 0.95 (95% CI, 0.93-0.97). Subgroup analysis indicated that SSRI use was significantly associated with an amelioration of erectile dysfunction (per 28 cDDD), with an HR of 0.95 (95% CI, 0.92-0.97). Conclusion: Male patients with DM and depression are at increased risk of sexual dysfunction. Antidepressant use had a small inverse association with the risk of sexual dysfunction in men with DM and depression. Antidepressants, in particular SSRIs, did not increase the risk of sexual dysfunction in this population.