Rubinwhitley4366

SUMOylation is a post-translational modification that regulates protein signalling and complex formation by adjusting the conformation or protein-protein interactions of the substrate protein. There is a compelling and rapidly expanding body of evidence that, in addition to SUMOylation of nuclear proteins, SUMOylation of extranuclear proteins contributes to the control of neuronal development, neuronal stress responses and synaptic transmission and plasticity. In this brief review we provide an update of recent developments in the identification of synaptic and synapse-associated SUMO target proteins and discuss the cell biological and functional implications of these discoveries.Aims To examine the effectiveness of extracorporeal magnetic stimulation for treatment of stress urinary incontinence DESIGN Systematic review and meta-analysis. Data resources Four electronic databases from inception to 18 May 2019. Review methods Two authors independently performed the search, assessed the methodological quality and extracted data. The final studies included in the analysis were selected after reaching consensus with the third author. Results A total of 20 studies were included in the systematic review and 12 of these in the meta-analysis. Quality assessment indicated that only eight of 17 randomized controlled trials had low risk in overall risk of bias, whereas all controlled trials had serious risk of bias. The weighted mean effect size of magnetic stimulation on quality of life, number of leakages, pad test outcomes and number of incontinence events was 1.045 (95% CI 0.409-1.681), -0.411 (95% CI 0.178-0.643), -0.290 (95% CI 0.025-0.556) and -0.747 (95% CI -1.122 to -0.372), respectively. Subgroup analysis revealed a significant difference in the type of quality of life measurement used. Sensitivity analyses revealed that a high degree of heterogeneity persisted even after omitting studies individually. Conclusions Extracorporeal magnetic stimulation may be effective in treating urinary incontinence and improving quality of life without major safety concerns. However, because of a high degree of heterogeneity among studies, inferences from the results must be made with caution. Impact We recommend that clinical nurses apply extracorporeal magnetic stimulation to treat stress urinary incontinence among female patients and encourage researchers to conduct further qualitative and quantitative studies to develop consistent content and dosage for the intervention. Study registration The review protocol was registered a priori and published online in the PROSPERO database of systematic reviews (www.crd.york.ac.uk/Prospero with the registration number #CRD42019138835).Mixed neuroendocrine and non-neuroendocrine neoplasms (MiNENs) of the digestive system represent a challenging task for both pathologists and clinicians. Their nomenclature has changed several times and their diagnostic criteria, classification, and clinical behaviour have been matter of debate over the past years. Although several attempts have been made to elucidate the pathogenesis and biology of MiNENs, some issues remain still open. This review will provide a historical background that helps to understand the evolution of the concept and nomenclature of mixed neoplasms a revision of the knowledge on this topic, including molecular aspects, to give the reader a comprehensive and practical overview on this challenging field of pathology a focus on the diagnostic criteria and on the determination of prognostic and predictive factors a description of the different tumour types in the different sites of origin.Background Dermatophytic infections have undergone unprecedented changes in India in the recent past. Clinical trials to find out the effectiveness of the four main oral antifungal drugs are lacking. Objectives We tested the effectiveness of oral fluconazole, griseofulvin, itraconazole and terbinafine in chronic and chronic relapsing tinea corporis, tinea cruris and tinea faciei in an investigator-initiated, randomized, pragmatic trial. Methods Two hundred patients with microscopy-confirmed tinea were allocated to four groups (50 patients in each group) fluconazole 5 mg kg-1 per day, griseofulvin 10 mg kg-1 per day, itraconazole 5 mg kg-1 per day and terbinafine 7·5 mg kg-1 per day. Allocation was performed by concealed block randomization and the patients were treated for 8 weeks or until cure. Effectiveness was calculated based on intention-to-treat analysis. The trial was registered with the Clinical Trials Registry India (CTRI/2017/04/008281). Results At 4 weeks, all drugs were similarly ineffective, with cure rates being 8% or less (P = 0·42). At 8 weeks, the numbers of patients cured were as follows fluconazole 21 (42%), griseofulvin seven (14%), itraconazole 33 (66%) and terbinafine 14 (28%) (P less then 0·001). Itraconazole was superior to fluconazole, griseofulvin and terbinafine (adjusted P ≤ 0·048). Relapse rates after 4 and 8 weeks of cure with the four treatments were not different (P ≥ 0·42). Numbers needed to treat (vs. ITD-1 griseofulvin), calculated on the basis of cure rates at 8 weeks, were as follows fluconazole 4, itraconazole 2 and terbinafine 8. Conclusions The results show limited effectiveness of all four antifungal drugs. In view of cure rates and the number needed to treat, itraconazole is the most effective drug, followed by fluconazole (daily), terbinafine and then griseofulvin, in chronic and chronic relapsing dermatophytosis in India.The endoplasmic reticulum (ER) is an important intracellular compartment in eukaryotic cells and has diverse functions, including protein synthesis, protein folding, lipid metabolism and calcium homeostasis. ER functions are disrupted by various intracellular and extracellular stimuli that cause ER stress, including the inhibition of glycosylation, disulphide bond reduction, ER calcium store depletion, impaired protein transport to the Golgi, excessive ER protein synthesis, impairment of ER-associated protein degradation and mutated ER protein expression. Distinct ER stress signalling pathways, which are known as the unfolded protein response, are deployed to maintain ER homeostasis, and a failure to reverse ER stress triggers cell death. Sphingolipids are lipids that are structurally characterized by long-chain bases, including sphingosine or dihydrosphingosine (also known as sphinganine). Sphingolipids are bioactive molecules long known to regulate various cellular processes, including cell proliferation, migration, apoptosis and cell-cell interaction.