Urology training in the developing world: The trainers\u27 perspective

Context: Despite producing some of the leading urologists in the world, urological training in the developing world is marred by inconsistency, and a lack of structure and focus on evidence-based practice. In this review we address these issues from the trainers\u27 perspective. Introduction: Teaching the art and science of urological practice is a demanding task. It not only involves helping the resident to develop the depth of cognitive knowledge, but also to have an appropriate surgical judgement, and an ability to act quickly but thoughtfully and, when necessary, decisively. Discussion: The surgeon must have compassion, communication skills, be perceptive and dedicated. Most importantly, however, he or she should have the ability to cut and suture. Not all of these can be inculcated in the training programme, even with the best of efforts. The selection of an appropriate candidate therefore becomes an issue of pivotal importance. The changing focus of urological training incorporates research and evidence-based practice as essential components. It is particularly important in the developing world, as there is a dearth of standardised practice models across the healthcare system. Encouraging female residents can be done by improving and tailoring the working conditions. The \u27brain drain\u27 is a major problem in the developing world, and bureaucracy and government need to take appropriate measures to provide high-quality healthcare facilities with room for professional growth. Conclusions: The future of urology will depend on improved education and training, leading to high-quality urological care, and to developing a service that is patient focused

Internal tides in a dendritic submarine canyon

Submarine canyons are a common geomorphological feature along continental slopes worldwide and often found to be ‘hotspots’ of internal tide activity. However, the majority of well-studied submarine canyons are simple linear incisions or have meandering morphology; internal tide energetics in branching (dendritic) canyons has not previously been investigated. Here we present a high-resolution (500-m) numerical modelling study of the internal tide within Whittard Canyon, a large, dendritic submarine canyon system that incises the Celtic Sea continental slope. A modified version of the Princeton Ocean Model is used to simulate the M2 (semidiurnal) internal tide in the Whittard Canyon region, verified against a hydrographic dataset collected by an autonomous ocean glider. Much of the internal tide energy entering Whittard Canyon originates to the southeast, along the Celtic Sea shelf break. Internal tide generation also occurs within the canyon itself, but is in part compensated by areas of negative energy conversion. Depth-integrated internal tide energy fluxes exceed 8 kW m−1 in the eastern limb of the canyon. The internal tide is topographically steered through the major limbs and along-canyon energy flux is bottom intensified, suggesting topographic focusing. The down canyon extent of bottom intensification closely corresponds to the point that along-canyon slope becomes near-critical to the semidiurnal internal tide. Energetically, the multiple limbs of Whittard Canyon behave differently, some are net sources of internal tide energy whilst others are net sinks. Internal tide energy dissipation also varies between the canyon limbs; bulk dissipation rates are 2.1-7.7 × 10−8 W kg−1 . In addition, the effect of bathymetric resolution on internal tide generation and propagation is investigated by progressively smoothing the model domain. Decreasing the bathymetric resolution reduces internal tide generation and energy dissipation in both Whittard Canyon and the model domain as a whole, however, internal tide energy flux into the canyon is not consistently changed. At least 1.5-km resolution bathymetry is required to adequately resolve the semidiurnal internal tide field in this region of complex topography

The genetics of neuroendocrine prostate cancers: a review of current and emerging candidates

Prostate cancer (PC) displays a strong familial link and genetic factors; genes regulating inflammation may have a pivotal role in the disease. Epigenetic changes control chromosomal integrity, gene functions, and, ultimately, carcinogenesis. The most widely studied epigenetic event in PC is aberrant DNA methylation (hypo- and hypermethylation); besides this, chromatin remodeling and micro RNA (miRNA) are other studied alterations in PC. These all lead to genomic instability and inappropriate gene expression. Causative dysfunction of histone modifying enzymes results in generic and locus-specific changes in chromatin remodeling. miRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen-receptor signaling and apoptosis. These epigenetic alterations have the potential to act as biomarkers for PC for screening and diagnosis as well as prognosis and follow-up. The variable biological potential for a newly diagnosed PC is one of the biggest challenges. The other major clinical problem is in the management of castration-resistant PC. Neuroendocrine (NE) differentiation is one of the putative explanations for the development of castration-resistant disease. Most advanced and poorly differentiated cancer does not produce prostate-specific antigen (PSA) in response to disease progression. Circulating and tissue biomarkers like chromogranin A (CgA) thus become important tools. There is the potential to use various genetic and epigenetic alterations and NE differentiation as therapeutic targets in the management of PC. However, we are still some distance from developing clinically effective tools. Valuable insights into the nature of NE differentiation in PC have been gained in the last decades, but additional understanding of its pathogenetic mechanisms is needed. This will help in devising novel therapeutic strategies to develop targeted therapies. CgA has the potential to become an important marker of advanced castration-resistant PC in cases where prostate-specific antigen can no longer be relied upon. Aberrant androgen-receptor signaling at various levels provides evidence of the importance of this pathway for the development of castration-resistant PC. Many epigenetic influences - in particular, the role of changing miRNA expression - provide valuable insights. Currently, massive sequencing efforts are underway to define important somatic genetic alterations (amplifications, deletions, point mutations, translocations) in PC, and these alterations hold great promise as prognostic markers and for predicting response to therapy

Non-surgical Management of Endodontic Periradicular Pathosis - A Clinical Research

Background: In most cases the aetiological factors of periradicular diseases are oral contaminants through the root canal or degenerating pulpal tissues. Therefore, the mere surgical removal of the periapical lesions without proper root canal disinfection and obturation will not result in the healing of the periradicular tissues. On the other hand, traditional surgical technique rather fearful and troublesome job due to various reasons. So successful apical and periapical repair depends on conventional root canal treatment - a non surgical procedure. Crucial to this management and ultimate success is the complete debridement of the root canal system, followed by three-dimensional obturation to seal both the apical foramen and coronal orifice. Objective: Thus, the purpose of this study was to clinically verify the possibility of management of periradicular pathosis by non-surgical conventional root canal therapy. Methods: The present study was a prospective observational study carried out in the department of Conservative Dentistry and Endodontics, Faculty of Dentistry, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka. Here, 75 cases of eondodontically involved symptomatic non-vital teeth having periradicular pathosis were managed by conventional root canal therapy. Result: After 18 months follow up with post operative clinical and radiological evaluations, in this study the final outcome was favourable-88%, doubtful-08 %, and failure-04%. Key words: Endodontics; Periarticular pathosisDOI: 10.3329/bsmmuj.v1i1.3694 BSMMU J 2008; 1(1): 22-2

Interaction between the AAA+ protease CIpXP and the adaptor protein SspB

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2010."June 2010." Cataloged from PDF version of thesis.Includes bibliographical references (p. 96-102).Proteolysis plays a vital role in cellular processes including regulatory pathways and protein quality control in prokaryotes and eukaryotes. ATP-dependent protein degradation is mediated by multimeric protease complexes, each consisting of a AAA+ ATPase and a peptidase component. Substrate selection by the proteases is a highly regulated process to ensure minimal errant protein degradation. Substrates are usually recognized by proteases through degradation tags or degrons. Accessory proteins called adaptors can also modulate substrate selection by proteases. These adaptors have the potential to affect substrate specificity as well as expand the repertoire of substrates that can be degraded by proteases. Understanding how proteases interact with a wide range of adaptors and substrates can provide valuable insight into the complex process of substrate selection. In this thesis, I have investigated the interaction between the AAA+ protease CIpXP and the adaptor protein SspB. The highly conserved N-terminal domain of the unfoldase CIpX interacts with SspB and other specific adaptor proteins and substrates. However, these binding partners do not use one simple sequence motif to mediate the protein-protein interaction. This diversity in protein-binding was further demonstrated by the cross-species CIpX-SspB interactions in Caulobacter crescentus and Escherichia coli. Despite little sequence homology, C. crescentus SspB (ccSspBa) and E. coli SspB (EcSspB) are able to interact with CIpX from either species. We analyzed these interactions to understand how the N-terminal domain of CIpX is able to recognize diverse adaptors and substrates while still retaining specificity. We identified the region important for interaction of ccSspBa with CIpX. Mutagenesis studies of the C-terminal region of the adaptor were conducted and the variants were tested for their ability to functionally interact with the CIpXP protease. Using these data and the results of peptide-binding experiments, we identified residues within the C-terminal region of ccSspBa that are important for tethering to CIpX. We also conducted functional and peptide-binding studies on the EcSspB CIpX-binding (XB) region. Interestingly, the two XB regions are very different in both length and sequence. However, despite this dissimilarity, competition studies argue that the two XB peptides bind to identical or overlapping sites of the CIpX N domains of C. crescentus and E. coli. This cross-species interaction between SspB and CIpX highlights how the CIpX N domain provides a versatile platform for binding a variety of adaptors and substrates. We also performed a proteomic-screen to investigate the effect of SspB on CIpXP substrate profile in E. coli. The preliminary data has provided a list of candidate SspB-interacting substrates, further analyses of which will contribute to the understanding of the biological impact of SspB on substrate selection by CIpXP.by Tahmeena Chowdhury.Ph.D

Current management of advanced and metastatic renal cell carcinoma.

Introduction:Unresectable renal cell carcinoma (RCC) is a technically incurable condition. Historically, RCC is resistant to chemotherapy and radiotherapy. Cytokine therapy was until recently considered the mainstay of treatment. However, responses are modest. Improvement in the understanding of the biology of RCC, particularly the hereditary types, is providing the basis for novel therapeutic targets. Our aim was to review the clinical utility of various systemic agents and surgery in the management of advanced RCC and suggest practice guidelines in the light of current literature. Materials and Methods: Evidence was collected by review of current literature, guidelines of the American and European associations and the national comprehensive cancer network. Results: Treatment of advanced RCC has recently undergone a major change with the development of targeted agents and potent angiogenesis inhibitors. Small-molecule multikinase inhibitors that target vascular endothelial growth factor receptors have a favorable toxicity profile and can prolong time to progression and preserve quality of life when used in newly diagnosed or previously treated Patients, bevacizumab enhances the response rate and prolongs disease control when added to interferon-alpha. Temsirolimus, a mammalian target of rapamycin inhibitor, prolongs the survival duration of Patients with poor-risk disease. All currently available agents have variable toxicity profile and they, at best, improve survival by a few months. Surgery still has a significant role in the management of stage IV RCC. Conclusions: Supportive care and surgery remain the mainstay of treatment even in the management of advanced and metastatic RCC. Systemic therapeutic agents are showing promising results

Internal tides in Whittard Canyon

Submarine canyons are common bathymetric features incising the shelf edge and are known to trap and focus internal waves leading to high levels of turbulent mixing. Whittard Canyon, located at the Celtic Sea shelf edge, is a dendritic canyon where little is known about the internal tide, yet where it is postulated to have a huge impact on biology within the canyon and also play a role in the generation of nepheloid layers. High-resolution simulations of the M2 tide in Whittard Canyon using a modified version of the Princeton Ocean Model are used to determine the generation, propogation, spatial structure and dissipation of the internal tide within the canyon. Shamrock canyon and Brenot Spur are identified as key remote sources of internal tide generation, which modulate local generation in a flux-conversion feedback mechanism which causes the observed assymmetry in barotropic-tobaroclinic conversion within the canyon limbs. Depth-integrated baroclinic energy flux within the canyon is elevated, but variably so in different limbs, with values reaching >8 kW m¡1. The eastern limb of the canyon is notable for being particularly energetic. Enhancement of near-bottom baroclinic tidal currents are seen within the canyon with velocities reaching 0.4 m s¡1. The three-dimensional structure exhibits bottom intensification due to topographic focusing by the steep canyon walls, and the dominantly supercritical limb heads. Within the upper canyon the internal tide exhibits a typical mode-1 structure. Cores of baroclinic energy flux, in a dominantly up-canyon direction, form over the depth range of 1000-2500 m and are correlated with potential source regions for nepheloid layers. The sensitivity of the model to bathymetric resolution is tested and it is found that using 500 m resolution bathymetry results in domain-averaged conversion rates higher than for the smoothed bathymetries tested, highlighting the need for high-quality, high-resolution bathymetric datasets

Partly standing internal tides in a dendritic submarine canyon observed by an ocean glider

An autonomous ocean glider is used to make the first direct measurements of internal tides within Whittard Canyon, a large, dendritic submarine canyon system that incises the Celtic Sea continental slope and a site of high benthic biodiversity. This is the first time a glider has been used for targeted observations of internal tides in a submarine canyon. Vertical isopycnal displacement observations at different stations fit a one-dimensional model of partly standing semidiurnal internal tides – comprised of a major, incident wave propagating up the canyon limbs and a minor wave reflected back down-canyon by steep, supercritical bathymetry near the canyon heads. The up-canyon internal tide energy flux in the primary study limb decreases from 9.2 to 2.0 kW m−1 over 28 km (a dissipation rate of View the MathML source), comparable to elevated energy fluxes and internal tide driven mixing measured in other canyon systems. Within Whittard Canyon, enhanced mixing is inferred from collapsed temperature-salinity curves and weakened dissolved oxygen concentration gradients near the canyon heads. It has previously been hypothesised that internal tides impact benthic fauna through elevated near-bottom current velocities and particle resuspension. In support of this, we infer order 20 cm s−1 near-bottom current velocities in the canyon and observe high concentrations of suspended particulate matter. The glider observations are also used to estimate a 1 °C temperature range and 12 μmol kg−1 dissolved oxygen concentration range, experienced twice a day by organisms on the canyon walls, due to the presence of internal tides. This study highlights how a well-designed glider mission, incorporating a series of tide-resolving stations at key locations, can be used to understand internal tide dynamics in a region of complex topography, a sampling strategy that is applicable to continental shelves and slopes worldwide

Tailored metabolic workup for urolithiasis – the debate continues

Abstract Urolithiasis is one of the commonest afflictions of the urinary tract. Stones are of various chemical compositions, some share some common etiology; but most are specific to the structure and composition of stone. In view of highly recurrent nature of this condition, it is logical to have strategies for prevention. However, due to multiple factors most patients receive no or fragmented information on prevention. The current controversy is to the extent of metabolic workup in adult first time stone former. This requires longitudinal studies to show benefit in prevention strategies. Patients at high risk can have recurrence in weeks to years, depending upon the composition and attending risk factor. They should be targeted with concentric and tailored prevention protocols. The major urological guidelines (EAU and AUA) recommend basic stone workup for all patients. However, indication for detailed workup are less well documented, so one potential solution is to tailor metaphylaxis strategies for individual patient

Comparison of Implant Success Rate Between Direct And Indirect Sinus Lift Procedure

Objective: The objective of the study is to compare gain in bone height and post-operative complications e with direct and indirect sinus lift procedure. Methods: This prospective clinical study was conducted at the department of Science of Dental Materials, University Medical and Dental college Faisalabad, in a period of one year from November 2021 to November 2022. For patients in the 20-50 years age range either gender with maxillary posterior edentulous regions but with a low sinus and deficient alveolar ridge, implant retained prostheses would be a viable option. Results: Results showed that pain and gingival inflammation resolved at 1st week postoperatively. These two parameters frequency was higher in patients with indirect method as compared to patients who were treated with direct method. Swelling was also settled in both treatment groups after 1st week postoperatively. However, frequency of swelling was higher in indirect method as that of direct method but the difference was not statistically significant. There is significant change in bone height postoperatively in both treatment groups. But gain in mean bone height was significantly higher in patients treated with direct approach. Conclusion: This study did not find a significant difference between direct versus indirect sinus lift procedures in terms of swelling, inflammation, and pain following surgery. Indirect sinus lifts, however, result in a significantly lower bone height gain than direct sinus lifts.   Key Words: Edentulism, Sinus lift procedures, Direct, Indirect, Bone height, Sinus surgery