Symphysiotomy: a viable approach for delayed management of posterior urethral injuries in children

PURPOSE: The outcome of symphysiotomy for accessing pelvic fracture related, obliterative urethral strictures is described. MATERIALS AND METHOD: In 7 boys and 3 girls 4 to 13 years old (mean age 6) surgical correction of a pelvic fracture related, obliterative urethral stricture was achieved through symphysiotomy. The stricture involved a prostatomembranous location in boys and complete vesicourethral distraction in girls. Patients were followed an average of 2.5 years (range 6 months to 4 years) by physical examination, urethrography and endoscopy. RESULTS: The stricture was successfully corrected in all patients and all void with a normal flow. All boys are continent but 2 of the 3 girls had early incontinence, which resolved with time in 1. In 2 of the 10 cases a previous attempt at perineal repair had already failed. No patient required urethrotomy or dilation and none had significant hemorrhage, fistulization, bladder hernia, chronic pain or secondary gait disturbance. CONCLUSIONS: Symphysiotomy is hereby revisited as a simple and effective approach for repairing traumatic posterior urethral injuries in the pediatric population. It can be performed instead of transpubic urethroplasty to manage long or otherwise complicated strictures.     

Significant Association of rs77493513 Polymorphism in 3'-UTR of the NRG1 Gene with the Risk of Multiple Sclerosis Disease

Metabolic Brain Disease - Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disease characterized by demyelination of the central nervous system (CNS). Neuregulin 1 (NRG1) is a...     

A novel fluorometric assay for aldo-keto reductase 1C3 predicts metabolic activation of the nitrogen mustard prodrug PR-104A in human leukaemia cells

Aldo-keto reductase 1C3 (AKR1C3, EC 1.1.1.188) metabolises steroid hormones, prostaglandins and xenobiotics, and activates the dinitrobenzamide mustard prodrug PR-104A by reducing it to hydroxylamine PR-104H. Here, we describe a functional assay for AKR1C3 in cells using the fluorogenic probe coumberone (a substrate for all AKR1C isoforms) in conjunction with a specific inhibitor of AKR1C3, the morpholylurea SN34037. We use this assay to evaluate AKR1C3 activity and PR-104A sensitivity in human leukaemia cells. SN34037-sensitive reduction of coumberone to fluorescent coumberol correlated with AKR1C3 protein expression by immunoblotting in a panel of seven diverse human leukaemia cell lines, and with SN34037-sensitive reduction of PR-104A to PR-104H. SN34037 inhibited aerobic cytotoxicity of PR-104A in high-AKR1C3 TF1 erythroleukaemia cells, but not in low-AKR1C3 Nalm6 pre-B cell acute lymphocytic leukaemia (B-ALL) cells, although variation in PR-104H sensitivity confounded the relationship between AKR1C3 activity and PR-104A sensitivity across the cell line panel. AKR1C3 mRNA expression showed wide variation between leukaemia patients, with consistently higher levels in T-ALL than B-ALL. In short term cultures from patient-derived paediatric ALL xenografts, PR-104A was more potent in T-ALL than B-ALL lines, and PR-104A cytotoxicity was significantly inhibited by SN34037 in T-ALL but not B-ALL. Overall, the results demonstrate that SN34037-sensitive coumberone reduction provides a rapid and specific assay for AKR1C3 activity in cells, with potential utility for identifying PR-104A-responsive leukaemias. However, variations in PR-104H sensitivity indicate the need for additional biomarkers for patient stratification.     

Applying Wells score to inconclusive perfusion only modified PIOPED II (Prospective Investigation of Pulmonary Embolism Diagnosis II) readings in order to optimize the lung scintigraphy diagnostic yield in acute pulmonary embolism detection

Annals of Nuclear Medicine - When using perfusion only modified PIOPED II criteria for PE detection, generated non-diagnostic scans are found to be the main diagnostic restriction. The objective of...     

Collapsin response‐mediator protein 5 (CRMP5) phosphorylation at threonine 516 regulates neurite outgrowth inhibition

The collapsin response‐mediator proteins (CRMPs) are multifunctional proteins highly expressed during brain development but down‐regulated in the adult brain. They are involved in axon guidance and neurite outgrowth signalling. Among these, the intensively studied CRMP2 has been identified as an important actor in axon outgrowth, this activity being correlated with the reorganisation of cytoskeletal proteins via the phosphorylation state of CRMP2. Another member, CRMP5, restricts the growth‐promotional effects of CRMP2 by inhibiting dendrite outgrowth at early developmental stages. This inhibition occurs when CRMP5 binds to tubulin and the microtubule‐associated protein MAP2, but the role of CRMP5 phosphorylation is still unknown. Here, we have studied the role of CRMP5 phosphorylation by mutational analysis. Using non‐phosphorylatable truncated constructs of CRMP5 we have demonstrated that, among the four previously identified CRMP5 phosphorylation sites (T509, T514, T516 and S534), only the phosphorylation at T516 residue was needed for neurite outgrowth inhibition in PC12 cells and in cultured C57BL/6J mouse hippocampal neurons. Indeed, the expression of the CRMP5 non‐phosphorylated form induced a loss of function of CRMP5 and the mutant mimicking the phosphorylated form induced the growth inhibition function seen in wildtype CRMP5. The T516 phosphorylation was achieved by the glycogen synthase kinase‐3β (GSK‐3β), which can phosphorylate the wildtype protein but not the non‐phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin‐binding property of CRMP5. Therefore, CRMP5‐induced growth inhibition is dependent on T516 phosphorylation through the GSK‐3β pathway. The findings provide new insights into the mechanisms underlying neurite outgrowth.     

Preparation of GO/SiO2/PEA as a new solid base catalyst for the green synthesis of some spirooxindole derivatives

Efficient and green one pot multi component synthesis of some spirooxindole derivatives in the presence of graphene oxide functionalized with 2-(1-piperazinyl) ethylamine (GO/SiO₂/PEA) as a solid base catalyst was studied. GO/SiO₂/PEA has been obtained through a two step reaction and characterized by Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), thermo gravimetric analysis (TGA), Raman spectroscopy and X-ray diffraction (XRD). Green reaction conditions, short reaction times, reusable catalyst and a high to excellent yield of products are some of the advantageous of the presented method.

Efficient and green one pot multi component synthesis of some spirooxindole derivatives in the presence of graphene oxide functionalized with 2-(1-piperazinyl) ethylamine (GO/SiO₂/PEA) as a solid base catalyst was studied.     

A rare sighting: left atrial appendage thrombus seen on transthoracic echocardiogram

The left atrial appendage(LAA)is the most common site of left atrial thrombus with more than 90％of thrombi formed within this structure.[1]Transesophageal echoc...