Nocturnal enuresis—theoretic background and practical guidelines

Nocturnal polyuria, nocturnal detrusor overactivity and high arousal thresholds are central in the pathogenesis of enuresis. An underlying mechanism on the brainstem level is probably common to these mechanisms. Enuretic children have an increased risk for psychosocial comorbidity. The primary evaluation of the enuretic child is usually straightforward, with no radiology or invasive procedures required, and can be carried out by any adequately educated nurse or physician. The first-line treatment, once the few cases with underlying disorders, such as diabetes, kidney disease or urogenital malformations, have been ruled out, is the enuresis alarm, which has a definite curative potential but requires much work and motivation. For families not able to comply with the alarm, desmopressin should be the treatment of choice. In therapy-resistant cases, occult constipation needs to be ruled out, and then anticholinergic treatment—often combined with desmopressin—can be tried. In situations when all other treatments have failed, imipramine treatment is warranted, provided the cardiac risks are taken into account

Protein phosphatase 2Cδ/Wip1 regulates phospho-p90RSK2 activity in lesional psoriatic skin

Mads K Rasmussen, Jakob Nielsen, Rasmus B Kjellerup, Stine M Andersen, Anne H Rittig, Claus Johansen, Lars Iversen, Borbala Gesser Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark Objectives: P90 ribosomal S6 kinase (RSK) 1 and 2 are serine/threonine protein kinases believed to mediate proliferation and apoptosis via the extracellular signal-regulated kinases (ERK1/2) signaling pathway. Macrophage migration inhibitory factor (MIF) and epidermal growth factor (EGF) are activators of this pathway and are elevated in the serum of patients with psoriasis compared with healthy controls. Studies on COS-7 cell cultures have shown that protein phosphatase 2Cδ (PP2Cδ) decreases the activity of RSK2 following EGF stimulation. We therefore hypothesize that PP2Cδ regulates RSK2 activity in psoriasis. Methods: In paired biopsies from nonlesional (NL) and lesional (L) skins, we analyzed the level of RSK1, 2 phosphorylation and the expression of PP2Cδ isoforms, integrin-linked kinase-associated serine/threonine phosphatase (ILKAP) and wild-type p53-induced phosphatase 1 (Wip1) by Western blotting, immunofluorescence and coimmunoprecipitation with monoclonal antibody for RSK2. The induction of Wip1 by MIF or EGF was studied in cultured normal human keratinocytes.Results: The protein level of RSK1, 2 phosphorylated at T573/T577 was significantly increased in L compared with NL psoriatic skin, while phosphorylation at S380/S386 was reduced in L compared with NL psoriatic skin when assayed by Western blotting and immunofluorescence microscopy. ILKAP expression was significantly higher in L than in NL skin, whereas Wip1 was expressed in similar amounts but showed increased coimmunoprecipitation with RSK2 in L compared with NL psoriatic skin. In cultured normal human keratinocytes stimulated with MIF, Wip1 phosphorylation and Wip1 expression were increased after 24 hours, but not when costimulated with dimethyl fumarate (DMF). The increased coimmunoprecipitation of Wip1 with RSK2 was significantly induced by EGF or MIF activation at 24 hours and could be significantly inhibited by DMF or the ERK1/2 inhibitor PD98059. Conclusion: The complex formation of Wip1 with RSK2 indicates a direct interaction reducing P-RSK2 (S386) activation in L skin and indicates that Wip1 has a role in the pathogenesis of psoriasis. Keywords: P90 RSK1, 2, EGF, MIF, PP2Cδ/ILKAP, PP2Cδ/Wip

Altered Primary Motor Cortex Structure, Organization, and Function in Chronic Pain:A Systematic Review and Meta-Analysis

Chronic pain can be associated with movement abnormalities. The primary motor cortex (M1) has an essential role in the formulation and execution of movement. A number of changes in M1 function have been reported in studies of people with chronic pain. This review systematically evaluated the evidence for altered M1 structure, organization, and function in people with chronic pain of neuropathic and non-neuropathic origin. Database searches were conducted and a modified STrengthening the Reporting of OBservational studies in Epidemiology checklist was used to assess the methodological quality of included studies. Meta-analyses, including preplanned subgroup analyses on the basis of condition were performed where possible. Sixty-seven studies (2,290 participants) using various neurophysiological measures were included. There is conflicting evidence of altered M1 structure, organization, and function for neuropathic and non-neuropathic pain conditions. Meta-analyses provided evidence of increased M1 long-interval intracortical inhibition in chronic pain populations. For most measures, the evidence of M1 changes in chronic pain populations is inconclusive. Perspective: This review synthesizes the evidence of altered M1 structure, organization, and function in chronic pain populations. For most measures, M1 changes are inconsistent between studies and more research with larger samples and rigorous methodology is required to elucidate M1 changes in chronic pain populations