These findings imply that baseline miR-409-3p activity in early female embryos is necessary for the expression of normal anxiety levels when they develop into adult females. In addition, elevated embryo miR-409-3p activity, possibly as a consequence of stress-induced elevation of its expression in sperm, may participate in, but may not be sufficient for, the induction of enhanced anxiety. This article is protected by copyright. All rights reserved.BACKGROUND AND OBJECTIVE A systematic review and meta-analysis of randomised controlled trials was undertaken to evaluate the effect of intrathecal dexmedetomidine (DEX) on the duration of postoperative analgesia, postoperative pain scores and incidences of adverse effects. Databases and Data Treatment Database search was performed from inception until January 2019. All randomised controlled trials analysing acute postoperative pain characteristics after intrathecal DEX administration in adults undergoing spinal anaesthesia for elective surgery were included. The primary outcome was postoperative analgesic duration, defined as the time to first analgesic request. The secondary outcomes included pain scores at 6, 12, and 24 post-operative hours and rates of hypotension, bradycardia, shivering and postoperative nausea and vomiting. RESULTS Twenty-four studies comprising a total of 1460 patients were included. Postoperative analgesic duration was prolonged with intrathecal DEX compared to placebo, with a pooled mean difference of 191.3 minutes (95% CI 168.8 to 213.8). Patients who received intrathecal DEX reported lower Visual Analogue Scale (VAS) scores at 24 postoperative hours compared with those patients receiving placebo, with a mean difference (95% CI) of -1.05 (-1.89 to -0.20, p=0.02). There were no differences in the incidence of adverse effects, except for a lower rate of postoperative shivering in the intrathecal DEX group (pooled RR 0.58, 95% CI 0.34 to 0.98, p=0.04). CONCLUSIONS Compared to placebo, intrathecal DEX prolonged postoperative analgesic duration, reduced 24-hour pain intensity and reduced the incidence of shivering without an increase in other adverse effects. This article is protected by copyright. All rights reserved.Autoimmune bullous diseases (AIBDs) are potentially life-threatening disorders comprising intra-epidermal/epithelial (pemphigus) and sub-epidermal/epithelial blistering diseases (pemphigoid and dermatitis herpetiformis). Corticosteroids and non-steroid immunomodulatory agents are the mainstays of treatment. Treatment can be challenging particularly in pemphigus, mucous membrane pemphigoid, and epidermolysis bullosa acquisita which may require more intense immunosuppressive approaches. This article is protected by copyright. All rights reserved.In their review Cai et al. reported that nonalcoholic fatty liver disease (NAFLD) is linked with a risk of atrial fibrillation (AF) partially attributed to metabolic syndrome (MetS) related components NAFLD consists the hepatic component of MetS or in insulin resistance (IR) syndrome. In this regard, we recently reported an influence of Helicobacter pylori infection (Hp-I) on MetS-related NAFLD severity.  https://www.selleckchem.com/  This article is protected by copyright. All rights reserved.Intracellular cAMP (i-cAMP) levels play an important role in acute myeloid leukemia (AML) cell proliferation and differentiation. Its levels are the result of cAMP production, degradation, and exclusion. We have previously described histamine H2 receptors and MRP4/ABCC4 as two potential targets for AML therapy. Acting through histamine H2 receptors histamine increases cAMP production/synthesis, while MRP4/ABCC4 is responsible for the exclusion of this cyclic nucleotide. In this study, we show that histamine treatment induces MRP4/ABCC4 expression, augmenting cAMP efflux and that histamine, in combination with MRP inhibitors, is able to reduce AML cell proliferation. Histamine, through histamine H2 receptor, increases i-cAMP levels and induces MRP4 transcript and protein levels in U937, KG1a, and HL-60 cells. Moreover, histamine induces MRP4 promoter activity in HEK293T cells transfected with histamine H2 receptor (HEK293T-H2 R). Our results support that the cAMP/Epac-PKA pathway, and not MEK/ERK nor PI3K/AKT signaling cascades, is involved in histamine mediated upregulation of MRP4 levels. Finally, the addition of histamine potentiates the inhibition of U937, KG1a, and HL-60 cell proliferation induced by MRP4 inhibitors. Our data highlight that the use of a poly-pharmacological approach aimed at different molecular targets would be beneficial in AML treatment. This article is protected by copyright. All rights reserved.BACKGROUND LASER therapy is now being proposed for the treatment of pelvic organ prolapse (POP) and urinary incontinence (UI). OBJECTIVES To systematically review the available literature on LASER therapy for POP and UI. SEARCH STRATEGY Pubmed, Web Of Science and Embase were searched for relevant articles, using a three concept (POP, UI, LASER therapy) search engine composed as (concept 1 OR concept 2) AND concept 3. SELECTION CRITERIA Only full text clinical studies in English. DATA COLLECTION AND ANALYSIS Data on patient characteristics, LASER setting, treatment outcome and adverse events were independently collected by two researchers. Due to the lack of methodological uniformity meta-analysis was not possible and results are presented narratively. MAIN RESULTS Thirty one studies recruiting 1530 adult women met the inclusion criteria. All studies showed significant improvement either on UI, POP or both, however the heterogeneity of LASER settings, application and outcome measures was huge. Only one study was a randomized controlled trial, two studies were controlled cohort studies. All three were on UI and used standardized validated tools. The risk of bias in the RCT was low on all seven domains; the controlled studies had a serious risk of bias. No major adverse events were reported, mild pain and burning sensation were the most common described adverse events. CONCLUSIONS All studies on vaginal and/or urethral LASER application for POP and UI report improvement, but the quality of studies needs to be improved. This article is protected by copyright. All rights reserved.