Student Perceptions of the Professional Behavior of Faculty Physicians

This study was conducted to obtain a baseline understanding of the professional behavior of clinical faculty physicians from the medical students’ perspective. Students completed a professionalism evaluation of supervising faculty at the end of each required third-year clerkship over a one year period. Results were analyzed by specific behaviors and across clerkships. Differences were noted in the frequency of the types of problems seen, and varied by clerkship discipline. The most common transgressions of professional behavior reported were the use of derogatory language towards other services or patients and the disrespectful treatment of others. Our study served to provide objective feedback to the faculty about student perceptions of faculty as role models for professionalism while on clinical rotations

Understanding the hydrogeochemical evolution of groundwater in coastal aquifers of southwest Bangladesh

Groundwater development in coastal aquifers of southwest Bangladesh is challenged by both natural and anthropogenic activities resulting in a landward migration of marine waters and increase in the risk of seawater intrusion. In some cases, infiltration of dissolved evaporite salts in the shallow aquifer and presence of connate water in the deep aquifer (DA) are the sources of groundwater salinity other than modern seawater intrusion. A detail investigation of these sources is imperative for a sustainable development and management of coastal aquifers. This work investigates the hydrogeochemical processes affecting groundwater chemistry by interpreting conventional plots, ionic delta, HFE-diagram, stable isotopes, and geochemical modelling. There are three hydrogeological units delineated in this area: upper shallow aquifer (USA) (<100 m bgl), lower shallow aquifer (LSA) (100-200 m bgl) and DA (below 200 m bgl). The hydrochemistry data reveal that the median values of total dissolved solids of the aquifers have a decreasing trend from top to bottom: USA with 7012 mg/l, LSA with 2622 mg/l and DA with 787 mg/l. Sodium is the dominant cation in all waters. The dominant anion in DA is HCO3 - , but in shallow aquifers Cl- . The main water type based on the classification of Stuyfzand (1989) is the brackish to saline NaCl type in the shallow aquifers. The Br- /Clratio and relatively enriched δ18O values in these NaCl waters suggest an origin derived from evaporate dissolution. Reverse cation exchange during intrusion, replacing Na+ with Ca2+, results in CaCl and CaMix water types. These waters infiltrate into the LSA. The water in the DA is mainly fresh NaHCO3+ type which originated by cation exchange from infiltrating fresh water. Ca2+ was replaced by Na+ due to the cation exchange, the water became undersaturated with respect to calcite and secondary calcite dissolution caused elevated bicarbonate concentrations. Near the present-day shoreline and at larger depths, the NaHCO3+ type water mixes with connate water, increasing salinity. The enriched δ18O values in the DA suggest an origin in a warmer climate, implying that this water has infiltrated a long time ago, much farther inland, probably during the Holocene climatic optimum. It can be expected that the salinization of the shallow aquifers will continue to increase if evaporite deposition and seasonal flooding occur. For a sustainable use of the groundwater resource in this coastal region and to prevent from even further worsening of water quality in its shallow aquifers, it is advised to develop future exploitations in the DA

Impacts of Large-Scale Groundwater Exploitation Based on Long-Term Evolution of Hydraulic Heads in Dhaka City, Bangladesh

Dhaka city has emerged as the fastest-growing megacity, having more than 20 million inhabitants, with a growth rate of 3.62%. Unplanned and rapid urbanization, coupled with exponential population growth, has significantly altered the groundwater dynamics in Dhaka city. This study concentrates on the evolution of long-term piezometric heads of the Upper Dupi Tila aquifer (UDA) and the Middle Dupi Tila aquifer (MDA) based on long-term hydrographs, piezometric maps and synthetic graphical overviews of piezometric trends. Due to over-exploitation, the piezometric level (PL) has declined deeper than −85 and −65 m PWD (Public Works Department reference datum) in UDA and MDA, respectively. The highest rate of decline was observed in the south-central to southeastern parts of the city both in UDA (4.0 m/year) and MDA (5.74 m/year). The results clearly show that the rates of decline in PL vary from 2.25 to 5.74 m/year in both aquifers of the city, and urban expansion has greatly affected the shape and extent of the depression cone over the past four decades. The magnitudes of the depression cones in both aquifers seem to pose a considerable threat to groundwater resources, indicating that the current exploitation is not sustainable at all.</jats:p

The impact of urbanization and rapid population growth on the groundwater regime in Dhaka city, Bangladesh

Dhaka city with an area of about 306 Km2 and a population of more than 20 million is located in the central part of Bangladesh. Immense and prolonged groundwater abstraction due to rapid unplanned urbanization and population blast in this city have led to significant decline in groundwater level in the last three decades. 78% of the supplied water comprises groundwater from the Dupi Tila Sandstone aquifer system. Hydrogeological and geophysical data aided to the delineation of three different aquifers (based on lithology): Upper Dupi Tila aquifer (UDA), Middle Dupi Tila aquifer (MDA) and Lower Dupi Tila aquifer (LDA). The evaluation of long-term hydrographs, piezometric maps and synthetic graphical overviews of piezometric trends in both the UDA and MDA depicts that the rate of dropping of groundwater level (GWL) is very substantial. Massive pumping in the city has altered its natural hydrologic system. The groundwater level has dropped on average 2.25 m/year and 2.8 m/year in UDA and MDA, respectively, in the whole city in 2018, whereas the average rate of decline in the center of the depression cone during this time was 4.0 m/year and 5.74 m/year respectively. Presently, the groundwater level elevation has declined to levels lower than -85 and -65 m PWD in UDA and MDA, respectively. The changes in pattern and magnitude of depression cones in UDA and MDA are directly associated with the city expansion and number of deep tube wells installed over a certain period in particular parts of the city. The depletion of GWL from 1980 to 2018 is very notable. There is only limited vertical recharge possible in the UDA and MDA as they are semi-confined aquifers, and only lateral flow mostly in the UDA and MDA from the surroundings is to be expected. In this regard the long-term management of groundwater resources in Dhaka city is urgently needed, otherwise the condition may go beyond control

Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer

Influence of routine computed tomography on predicted survival from blunt thoracoabdominal trauma

Item does not contain fulltextINTRODUCTION: Many scoring systems have been proposed to predict the survival of trauma patients. This study was performed to evaluate the influence of routine thoracoabdominal computed tomography (CT) on the predicted survival according to the trauma injury severity score (TRISS). PATIENTS AND METHODS: 1,047 patients who had sustained a high-energy blunt trauma over a 3-year period were prospectively included in the study. All patients underwent physical examination, conventional radiography of the chest, thoracolumbar spine and pelvis, abdominal sonography, and routine thoracoabdominal CT. From this group with routine CT, we prospectively defined a selective CT (sub)group for cases with abnormal physical examination and/or conventional radiography and/or sonography. Type and extent of injuries were recorded for both the selective and the routine CT groups. Based on the injuries found by the two different CT algorithms, we calculated the injury severity scores (ISS) and predicted survivals according to the TRISS methodology for the routine and the selective CT algorithms. RESULTS: Based on injuries detected by the selective CT algorithm, the mean ISS was 14.6, resulting in a predicted mortality of 12.5%. Because additional injuries were found by the routine CT algorithm, the mean ISS increased to 16.9, resulting in a predicted mortality of 13.7%. The actual observed mortality was 5.4%. CONCLUSION: Routine thoracoabdominal CT in high-energy blunt trauma patients reveals more injuries than a selective CT algorithm, resulting in a higher ISS. According to the TRISS, this results in higher predicted mortalities. Observed mortality, however, was significantly lower than predicted. The predicted survival according to MTOS seems to underestimate the actual survival when routine CT is used

Acyl-Protein Thioesterase 2 Catalizes the Deacylation of Peripheral Membrane-Associated GAP-43

An acylation/deacylation cycle is necessary to maintain the steady-state subcellular distribution and biological activity of S-acylated peripheral proteins. Despite the progress that has been made in identifying and characterizing palmitoyltransferases (PATs), much less is known about the thioesterases involved in protein deacylation. In this work, we investigated the deacylation of growth-associated protein-43 (GAP-43), a dually acylated protein at cysteine residues 3 and 4. Using fluorescent fusion constructs, we measured in vivo the rate of deacylation of GAP-43 and its single acylated mutants in Chinese hamster ovary (CHO)-K1 and human HeLa cells. Biochemical and live cell imaging experiments demonstrated that single acylated mutants were completely deacylated with similar kinetic in both cell types. By RT-PCR we observed that acyl-protein thioesterase 1 (APT-1), the only bona fide thioesterase shown to mediate deacylation in vivo, is expressed in HeLa cells, but not in CHO-K1 cells. However, APT-1 overexpression neither increased the deacylation rate of single acylated GAP-43 nor affected the steady-state subcellular distribution of dually acylated GAP-43 both in CHO-K1 and HeLa cells, indicating that GAP-43 deacylation is not mediated by APT-1. Accordingly, we performed a bioinformatic search to identify putative candidates with acyl-protein thioesterase activity. Among several candidates, we found that APT-2 is expressed both in CHO-K1 and HeLa cells and its overexpression increased the deacylation rate of single acylated GAP-43 and affected the steady-state localization of diacylated GAP-43 and H-Ras. Thus, the results demonstrate that APT-2 is the protein thioesterase involved in the acylation/deacylation cycle operating in GAP-43 subcellular distribution

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved