TIPS in Variceal Bleeding: New and Old Indications

Variceal bleeding is one of the most dreaded complications of cirrhosis and its occurrence is associated with significant morbidity and mortality. During the past 30 years preventative therapies have reduced the risk of the first variceal bleed. Once variceal bleeding occurs use of pharmacologic and endoscopic therapies prevent rebleeding in most patients. The existing recommendations are that TIPS only be used in those patients who fail medical therapy. We reviewed recent literature focusing on the role of early TIPS in management of acute variceal hemorrhage and prevention of re-bleeding.     

Screening and identification of bioactive compounds from citrus against non-structural protein 3 protease of hepatitis C virus genotype 3a by fluorescence resonance energy transfer assay and mass spectrometry

BACKGROUNDHepatitis C virus genotype 3a (HCV G3a) is highly prevalent in Pakistan. Due to the elevated cost of available Food and Drug Administration-approved drugs against HCV, medicinal natural products of potent antiviral activity should be screened for the cost-effective treatment of the disease. Furthermore, from natural products, active compounds against vital HCV proteins like non-structural protein 3 (NS3) protease could be identified to prevent viral proliferation in the host.AIMTo develop cost-effective HCV genotype 3a NS3 protease inhibitors from citrus fruit extracts.METHODSFull-length NS3 without co-factor non-structural protein 4A (NS4A) and codon optimized NS3 protease in fusion with NS4A were expressed in Escherichia coli. The expressed protein was purified by metal ion affinity chromatography and gel filtration. Citrus fruit extracts were screened using fluorescence resonance energy transfer (FRET) assay against the protease and polyphenols were identified as potential inhibitors using electrospray ionization-mass spectrometry (MS)/MS technique. Among different polyphenols, highly potent compounds were screened using molecular modeling approaches and consequently the most active compound was further evaluated against HCV NS4A-NS3 protease domain using FRET assay.RESULTSNS4A fused with NS3 protease domain gene was overexpressed and the purified protein yield was high in comparison to the lower yield of the full-length NS3 protein. Furthermore, in enzyme kinetic studies, NS4A fused with NS3 protease proved to be functionally active compared to full-length NS3. So it was concluded that co-factor NS4A fusion is essential for the purification of functionally active protease. FRET assay was developed and validated by the half maximal inhibitory concentration (IC₅₀) values of commercially available inhibitors. Screening of citrus fruit extracts against the native purified fused NS4A-NS3 protease domain showed that the grapefruit mesocarp extract exhibits the highest percentage inhibition 91% of protease activity. Among the compounds identified by LCMS analysis, hesperidin showed strong binding affinity with the protease catalytic triad having S-score value of -10.98.CONCLUSIONFused NS4A-NS3 protease is functionally more active, which is effectively inhibited by hesperidin from the grapefruit mesocarp extract with an IC₅₀ value of 23.32 µmol/L.     

The influence of covalent and non-covalent functionalization of GNP based nanofluids on its thermophysical,rheological and suspension stability properties

Covalent functionalization (CF-GNPs) and non-covalent functionalization (NCF-GNPs) approaches were applied to prepare graphene nanoplatelets (GNPs). The impact of using four surfactants (SDS, CTAB, Tween-80, and Triton X-100) was studied with four test times (15, 30, 60, and 90 min) and four weight concentrations. The stable thermal conductivity and viscosity were measured as a function of temperature. Fourier transform infrared spectroscopy (FTIR), thermo-gravimetric analysis (TGA), X-ray diffraction (XRD) and Raman spectroscopy verified the fundamental efficient and stable CF. Several techniques, such as dispersion of particle size, FESEM, FETEM, EDX, zeta potential, and UV-vis spectrophotometry, were employed to characterize both the dispersion stability and morphology of functionalized materials. At ultrasonic test time, the highest stability of nanofluids was achieved at 60 min. As a result, the thermal conductivity displayed by CF-GNPs was higher than NCF-GNPs and distilled water. In conclusion, the improvement in thermal conductivity and stability displayed by CF-GNPs was higher than those of NCF-GNPs, while the lowest viscosity was 8% higher than distilled water, and the best thermal conductivity improvement was recorded at 29.2%.

Covalent functionalization (CF-GNPs) and non-covalent functionalization (NCF-GNPs) approaches were applied to prepare graphene nanoplatelets (GNPs).     

Costs of laparoscopic and open liver and pancreatic resection: A systematic review

AIM: To study costs of laparoscopic and open liver and pancreatic resections, all the compiled data from available observational studies were systematically reviewed.METHODS: A systematic review of the literature was performed using the Medline, Embase, PubMed, and Cochrane databases to identify all studies published up to 2013 that compared laparoscopic and open liver [laparoscopic hepatic resection (LLR) vs open liver resection (OLR)] and pancreatic [laparoscopic pancreatic resection (LPR) vs open pancreatic resection] resection. The last search was conducted on October 30, 2013.RESULTS: Four studies reported that LLR was associated with lower ward stay cost than OLR (2972 USD vs 5291 USD). The costs related to equipment (3345 USD vs 2207 USD) and theatre (14538 vs 11406) were reported higher for LLR. The total cost was lower in patients managed by LLR (19269 USD) compared to OLR (23419 USD). Four studies reported that LPR was associated with lower ward stay cost than OLR (6755 vs 9826 USD). The costs related to equipment (2496 USD vs 1630 USD) and theatre (5563 vs 4444) were reported higher for LPR. The total cost was lower in the LPR (8825 USD) compared to OLR (13380 USD).CONCLUSION: This systematic review support the economic advantage of laparoscopic over open approach to liver and pancreatic resection.     

Cement pulmonary embolism after percutaneous vertebroplasty and kyphoplasty: An overview

BACKGROUND: Because of the aging of the American population, osteoporotic vertebral fractures are becoming a common problem in the elderly. Minimally invasive percutaneous vertebral augmentation techniques have gained a great deal of importance in relieving the pain associated with these fractures, and are becoming the standard of care. METHODS: These procedures involve the injection of polymethylmethacrylate (PMMA) into the vertebral body. However, these techniques have their complications, and among these, pulmonary embolism is one of the most feared. It is attributable to the passage of cement into the pulmonary vasculature. After encountering a case of PMMA embolism in our practice, we decided to highlight this topic and discuss the incidence, clinical presentation, diagnosis, and treatment of cement pulmonary embolisms.     

Comparison of immediate complete denture, tooth and implant-supported overdenture on vertical dimension and muscle activity

PURPOSE

To compare the changes in the occlusal vertical dimension, activity of masseter muscles and biting force after insertion of immediate denture constructed with conventional, tooth-supported and Implant-supported immediate mandibular complete denture.

MATERIALS AND METHODS

Patients were selected and treatment was carried out with all the three different concepts i.e, immediate denture constructed with conventional (Group A), tooth-supported (Group B) and Implant-supported (Group C) immediate mandibular complete dentures. Parameters of evaluation and comparison were occlusal vertical dimension measured by radiograph (at three different time intervals), Masseter muscle electromyographic (EMG) measurement by EMG analysis (at three different positions of jaws) and bite force measured by force transducer (at two different time intervals). The obtained data were statistically analyzed by using ANOVA-F test at 5% level of significance. If the F test was significant, Least Significant Difference test was performed to test further significant differences between variables.

RESULTS

Comparison between mean differences in occlusal vertical dimension for tested groups showed that it was only statistically significant at 1 year after immediate dentures insertion. Comparison between mean differences in wavelet packet coefficients of the electromyographic signals of masseter muscles for tested groups was not significant at rest position, but significant at initial contact position and maximum voluntary clench position. Comparison between mean differences in maximum biting force for tested groups was not statistically significant at 5% level of significance.

CONCLUSION

Immediate complete overdentures whether tooth or implant supported prosthesis is recommended than totally mucosal supported prosthesis.     

Diabetologist's perspective on practice of evidence based diabetes management in India

Diabetes demands early diagnosis, prompt treatment, continuous monitoring and follow up. Physicians play a pivotal role in diabetes management. However, evidence suggests that sub-optimal knowledge of guidelines and other issues may lead to ineffective management and poor patient outcomes. The aim of this research was to identify clinical diabetologist's perspectives on evidence based diabetes management, benefits of and barriers to the practice of evidence based guidelines in management of type 2 diabetes. Clinical diabetologists were administered a semi-structured questionnaire. Qualitative responses were analysed to identify key words, phrases and concepts from respondents. Majority of diabetologist (78.2%) preferred ADA guidelines alone or in combination with others guidelines where as 12.7% diabetologist follow all the guidelines on case by case basis. 27% and 25% diabetologists opined that guidelines ensure uniform standard of care across patient and achievement of diabetes management goals respectively. Poor awareness among physicians (22.7%), western guidelines being not applicable to Indian patients (22.7%), cost to patient (18.2%) were some of the barrier to practice of evidence based diabetes management. Some of the mechanism suggested to improve the practice of evidence based diabetes management included education of physicians in EBM (28.9%), making practice of evidence based guidelines legally binding (10.5%) and wider dissemination of existing guidelines (7.8%).