MGRN1 depletion promotes intercellular adhesion in melanoma by upregulation of E-cadherin and inhibition of CDC42.

Mahogunin Ring Finger 1 is an E3-ubiquitin ligase encoded by the color gene MGRN1. Our previous in vitro and in vivo studies demonstrated that Mgrn1 deletion in mouse melanoma cells induced cell differentiation and adhesion, and decreased cell motility and invasion on collagen I, and lung colonization in an in vivo model. Here, we investigated the role of MGRN1 on human melanoma cell morphology, adhesion and expression of genes/proteins involved in an EMT-like transition. We demonstrated that wild-type BRAF human melanoma cells adopted a clustering-like morphology on collagen I, with permanent MGRN1 abrogation resulting in bigger cell clusters. Enhanced intercellular adhesion was mostly mediated by induction of E-cadherin and higher co-localization with ß-catenin. Transcriptional upregulation of E-cadherin likely occurred through downregulation of the ZEB1 repressor. Finally, pulldown assays showed reduced activation of CDC42 in the absence of MGRN1, which was reverted after E-cadherin silencing. Overall, these findings highlight a new MGRN1-dependent pathway regulating melanoma cell shape, motility, and invasion potential.

Oxycodone improves pain control and quality of life in anticonvulsant-pretreated spinal cord-injured patients with neuropathic pain.

STUDY DESIGN: A 3-month follow-up, observational, prospective, multicenter, study in traumatic spinal cord-injured (SCI) patients with neuropathic pain (NP). OBJECTIVES: To assess the effectiveness and safety of oxycodone treatment in SCI patients with anticonvulsants-refractory NP. SETTING: 'Spinal injury follow-up units' throughout Spain. METHODS: Data regarding NP characteristics were collated from male and female adults with traumatic SCI and difficult-to-control central NP of moderate-to-severe intensity (visual analog scale (VAS) ≥4) persisting ≥1 month, who had been para- or tetraplegic for ≥2 months, had been previously treated with anticonvulsants and were now treated with oxycodone. RESULTS: In all, 54 out of the 57 patients recruited were assessable. A total of 81% were men and the mean age was 46.4. Patients were treated with oxycodone, 83% combined with anticonvulsant. Pain intensity (VAS: 7.1 ± 1.3-4.3 ± 1.7) and Lattinen total score (13.2 ± 3-7.7 ± 3.4) decreased significantly (P < 0.001) along the study. No patient got worse regarding pain impact on physical activity and on sleep (Lattinen scale). EQ-5D VAS showed a trend to increase (P = 0.061) and the index of preference values increased significantly from baseline to month 3 (0.26-0.62; P < 0.001). A total of 53.7% patients showed at least one treatment-related adverse event, with constipation being the most frequent one (33.3%). CONCLUSION: Oxycodone treatment, mostly in combination with anticonvulsants, in SCI patients with NP decreases pain intensity, improves health-related quality of life and diminishes the impact of pain on physical activity and sleep.

Intermittent catheterisation with hydrophilic-coated catheters (SpeediCath) reduces the risk of clinical urinary tract infection in spinal cord injured patients: a prospective randomised parallel comparative trial.

OBJECTIVES: To compare the performance of SpeediCath hydrophilic-coated catheters versus uncoated polyvinyl chloride (PVC) catheters, in traumatic spinal cord injured patients presenting with functional neurogenic bladder-sphincter disorders. METHODS: A 1-year, prospective, open, parallel, comparative, randomised, multi centre study included 123 male patients, > or =16 y and injured within the last 6 months. Primary endpoints were occurrence of symptomatic urinary tract infection (UTI) and hematuria. Secondary endpoints were development of urethral strictures and convenience of use. The main hypothesis was that coated catheters cause fewer complications in terms of symptomatic UTIs and hematuria. RESULTS: 57 out of 123 patients completed the 12-month study. Fewer patients using the SpeediCath hydrophilic-coated catheter (64%) experienced 1 or more UTIs compared to the uncoated PVC catheter group (82%) (p = 0.02). Thus, twice as many patients in the SpeediCath group were free of UTI. There was no significant difference in the number of patients experiencing bleeding episodes (38/55 SpeediCath; 32/59 PVC) and no overall difference in the occurrence of hematuria, leukocyturia and bacteriuria. CONCLUSIONS: The results indicate that there is a beneficial effect regarding UTI when using hydrophilic-coated catheters.

[Do the incontinent patients improve their equality of life using a humidity detector device?]. / Mejora un detector de humedad la calidad de vida de los pacientes con incontinencia urinaria?: un estudio piloto.

BACKGROUND: To evaluate the effect of a humidity detector device on the quality of life of patients with urinary incontinence IU. METHOD: Quasi-experimental study: a series of ten cases followed for a month. The devices were placed and the questionnaires filled in before and after using it for at least ten hours a day during a month. Health related quality of life was assessed through the questionnaires for IU convalidated and adapted to our specific environment: Urogenital Inventory Distress (UDI) and Incontinence Impact Questionary (IIQ). An improvement of 58 points by a four option Likert scale was considered a positive impact in the quality of life (IIQ). The scores obtained in UDI and IIQ are described before and after use the device and paried T test and Wilcoxon sign test were carried out to compare the scores obtained in each instance. The capacity to detect a difference of 58 points on the UDI scale was calculated (minimum relevant difference). A binomial test was undertaken to ascertain a probability of achieving an increase in the above mentioned index which would exceed the clinical relevance threshold. RESULTS: Average increase in IIQ improvement: x = 5.48 (Std Error = 20.43) 95% CI = -34.56 to 45.56. Average increase in UDI improvement: x = -11.87 (Std Error = 20.70) 95% IC = -52.45 to 28.70. The power of the analysis to detect as relevant a difference of a 588 point increase in IIQ 71.1% and probability of obtaining a relevant improvement in the questionnaire IIQ 10% (IC 95%) 0% to 39.4%. CONCLUSIONS: A negative impact in the Quality of Life due to frequent changes of incontinence pads.