Bladder outlet physiology in the context of lower urinary tract dysfunction

Physiological function of the bladder outlet is complex and symptomatic consequences can result from outlet dysfunction. Within the outlet, smooth, and skeletal muscles constitute the contractile apparatus, but additional cell types include interstitial cells and neuroendocrine cells, and various transmitters are present in the innervation, raising the possibility of unrecognized functional subtleties. Key outlet functions are; maintained closure for urine storage, increased closure (guarding) during exertion, sustained opening for voiding, transient opening for territorial marking in animals and orthograde male ejaculation. These are co-ordinated by several spinal and higher CNS centers, with overlap of the somatic, sympathetic and parasympathetic nervous systems. During voiding, urethral afferents may be important in maintaining detrusor contraction until completion of bladder emptying. Some of the bladder outlet afferents may be shared with the anal sphincter. Dysfunction of the outlet leads to conditions such as retrograde ejaculation, Fowler's syndrome, and detrusor sphincter dyssynergia. Urethral relaxation during urine storage may lead to urinary urgency, which may be misleadingly labeled as overactive bladder. Research priorities are numerous, including; peripheral cellular integrative physiology, interactions with other pelvic organs, interconnectivity of the CNS centers at all levels of the neuraxis, and standardized animal models of outlet functions such as reflex-driven voiding.     

Effect of ultrasonication with EDTA or MTAD on smear layer, debris and erosion scores

The purpose of this study was to compare the effects of ultrasonication with ethylenediaminetetraacetic acid (EDTA) and a mixture of tetracycline isomer, an acid, and a detergent (MTAD) as final canal irrigants on the smear layer, debris and erosion scores. Fifty-eight extracted single-rooted human teeth were instrumented with ProTaper rotary files up to size F3. According to the final irrigation regimen, the samples were distributed into the following groups: EDTA, MTAD, EDTA ultrasonicated for 1 min, and MTAD ultrasonicated for 1 min. The smear layer, debris and erosion scores were recorded at the apical, middle, and coronal third of each canal using a scanning electron microscope. Data were subjected to statistical evaluation using the Kruskal-Wallis and Mann-Whitney tests (P < 0.05). There were no significant differences in smear layer or debris removal between the experimental groups. EDTA caused significantly more erosion at the middle level than MTAD. Also EDTA resulted in more erosion at the coronal level than MTAD when subjected to ultrasonication. Ultrasonic activation of EDTA significantly increased its erosive effects at the middle and coronal levels. Based on the present findings, MTAD appears to cause less dentinal erosion while allowing proper removal of the smear layer and debris.     

How should we assess knowledge translation in research organizations; designing a knowledge translation self-assessment tool for research institutes (SATORI)

Background  

The knowledge translation self-assessment tool for research institutes (SATORI) was designed to assess the status of knowledge translation in research institutes. The objective was, to identify the weaknesses and strengths of knowledge translation in research centres and faculties associated with Tehran University of Medical Sciences (TUMS).     

Fruits and vegetables consumption and esophageal squamous cell carcinoma: a case-control study

The authors examined the association of food group intakes and the risk of esophageal squamous cell carcinoma (SCC) in a hospital-based case-control study in Iran. In total, 47 patients with esophageal SCC and 96 controls underwent face-to-face private interviews. Usual dietary intake was assessed using a semiquantitative food frequency questionnaire. Multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals. Cases had higher tobacco consumption and symptomatic gastresophageal reflux, whereas controls had higher mean body mass index (25.3 vs. 20.4) and years of education. A protective independent effect was observed for the highest tertile of total fruit consumption (OR: 0.13, CI: 0.04-0.45, P value = 0.001). Within the group of fruits, a significant inverse association was observed for bananas and kiwis (P for trends: 0.03 and 0.02, respectively). The risk of SCC decreased monotonically with increasing intake frequency of oranges (P value for trend = 0.01). The effect of total vegetable consumption on esophageal SCC was not significant, although a reduction in risk was observed in the highest tertile of intake (OR: 0.66, CI: 0.23-1.87, P value = 0.43). The results of the present study suggest a reasonable association between fruit consumption and esophageal SCC in a Middle Eastern high-risk population.     

Synthesis and structural studies of pentacycloundecane-based HIV-1 PR inhibitors: a hybrid 2D NMR and docking/QM/MM/MD approach

Pentacycloundecane (PCU) lactam-peptide based HIV protease inhibitors were synthesized and nanomolar activity against the resistance-prone wild type C-South African HIV protease is reported. NMR investigations indicated that the activity is related to the chirality of the PCU moiety and its ability to induce conformations of the coupled peptide side chain. EASY-ROESY NMR experiments gave information about the 3D structure of the cage peptides and 3D solution structure could be linked to the experimental IC₅₀ activity profile of the considered inhibitors. QM/MM/MD simulations of the inhibitors in solution confirmed the NMR observed conformations. Docking experiments and QM/MM/MD simulations of the inhibitor-HIV PR complexes were also performed. These computational results complimented the experimental inhibition activities and enabled us to report a unique binding mode for PCU-based inhibitors at the active site of HIV-protease enzyme. A conserved hydrogen bonding pattern between the norstatine type functional group of the PCU hydroxylactam and active site residues, ASP25/ASP25′, was observed in all active compounds. The biological significance and possible mode of inhibition by PCU-based HIV PR inhibitors discussed herein provide us with a deeper understanding of the mode of action of these novel inhibitors. The PCU-peptides are between 6000 and 8500 time less toxic to human MT-4 cells than Lopinavir. This potentially creates new application avenues for these putative inhibitors to be investigated against a vast number of other disease-related proteases.