Comparative Antiviral Efficacy of Generic Sofosbuvir versus Brand Name Sofosbuvir with Ribavirin for the Treatment of Hepatitis C.

BACKGROUND: Chronic hepatitis C infection is a major cause for liver failure and liver cancer and can be treated with highly effective all oral directly acting antiviral (DAA) drugs. Generic versions of these DAAs are available in India. METHOD: This was an open-label, single-center, prospective, nonrandomized observational study for the comparative safety and efficacy of generic versus brand name sofosbuvir with ribavirin therapy for chronic hepatitis C infection (all genotypes). Between December 2014 and December 2015, 66 patients received either generic sofosbuvir (400mg) or brand name SOLVALDI (400mg) with weight based ribavirin for 24 weeks in a single multispecialty hospital in Mumbai. Monitoring viral loads and safety labs was performed as per national guidelines. RESULTS: Sustained virologic response was 72.4% versus 75.7% (p=0.78) among patients treated with generics and SOVALDI, respectively. At 4 weeks on-treatment, approximately 90% of patients from both groups had undetectable or below the lower limit of quantification. Change in hemoglobin was comparable in both groups (p=0.26). CONCLUSION: Generic versions of sofosbuvir reported in this study are safe and efficacious to treat hepatitis C. However, bioequivalency studies of all generic DAAs need to be performed before wider use of such drugs for the treatment of hepatitis C.

Association between antidepressant prescribing and suicide rates in OECD countries: an ecological study.

INTRODUCTION: We have conducted an ecological study to assess the association between antidepressant prescribing and suicide rates using the Organisation for Economic Co-operation and Development (OECD) health data, making this the largest ecological study in recent times. METHOD: Data were derived for the years 1995-2008 from the OECD health data set. The residuals for all variables were adjusted for country and year within each country. These were then analysed to identify predictors of suicide rate. Pearson's rank correlation coefficient and linear regression model were employed to assess associations and identify significant predictors of suicide rate. RESULTS: Suicide rate has significant positive correlations with antidepressant rates (p=0.031) and unemployment (p=0.028). It also has a significant negative correlation with inpatient psychiatric beds (p=0.039). The actual coefficients are less than ±0.16, indicating weak relationships. After adjusting for other variables, the only variable that is a statistically significant predictor of suicide rate is antidepressant prescribing (p=0.005, r²=0.09). DISCUSSION: Our analysis using this large data set suggests a statistically significant, albeit weak positive, association between antidepressant prescribing and suicide rates.

Identification of irradiated cashew nut by electron paramagnetic resonance spectroscopy.

Cashew nut samples were irradiated at gamma-radiation doses of 0.25, 0.5, 0.75, and 1 kGy, the permissible dose range for insect disinfestation of food commodities. A weak and short-lived triplet (g = 2.004 and hfcc = 30 G) along with an anisotropic signal (g perpendicular = 2.0069 and g parallel = 2.000) were produced immediately after irradiation. These signals were assigned to that of cellulose and CO 2 (-) radicals. However, the irradiated samples showed a dose-dependent increase of the central line (g = 2.0045 +/- 0.0002). The nature of the free radicals formed during conventional processing such as thermal treatment was investigated and showed an increase in intensity of the central line (g = 2.0045) similar to that of irradiation. Characteristics of the free radicals were studied by their relaxation and thermal behaviors. The present work explores the possibility to identify irradiated cashew nuts from nonirradiated ones by the thermal behaviors of the radicals beyond the period, when the characteristic electron paramagnetic resonance spectral lines of the cellulose free radicals have essentially disappeared. In addition, this study for the first time reports that relaxation behavior of the radicals could be a useful tool to distinguish between roasted and irradiated cashew nuts.

Induction of pullulanase production in Bacillus cereus FDTA-13.

Studies were carried out on the production of pullulanase by a newly isolated strain Bacillus cereus FDTA-13. High titres of the enzyme were obtained in a medium containing branched polysaccharides. To further enhance the yield, induction of pullulanase using conventional inducers were studied. Maltooligosaccharides (maltose to maltotetraose) when added in the medium individually, or in a 1:1 combination of maltotriose and maltotetraose resulted different levels of pullulanase compared to control. Growth under carbon limited conditions (5 g l(-1)) with inducers resulted remarkably enhanced pullulanase activity. Pullulanase activity was severely repressed in presence of glucose. Low levels of pullulanase was observed in nitrogen limited medium, even with combinations of several maltosaccharides.

Extraction and quantification of gymnemic acids through gymnemagenin from callus cultures of Gymnema sylvestre.

The phyto-constituents of Gymnema sylvestre are used in the treatment of diabetes and obesity. The present work reports on the extraction of gymnemic acid through gymnemagenin from callus cultures of G. sylvestre. Components were separated on pre-coated silica gel 60 GF254 plates with chloroform:methanol (8:2) and scanned using a densitometric scanner at 205 nm in the near-UV region. Linearity of determination of gymnemagenin was observed in the range 2-10 microg. The average percentage recovery of gymnemagenin from leaf callus extracts was 98.9+/-0.3.

Differential distribution of sequence variations in HPV-16 E6.

OBJECTIVE: The E6 regions of the oncogenic human papillomaviruses (HPVs) are important in carcinogenesis and immune recognition. We examined the E6 DNA sequence from HPV-16-associated cervical cancers to determine the frequency and degree of variation from the consensus sequence in selected populations. METHODS: Samples positive for HPV-16 were analyzed using polymerase chain reaction followed by automated DNA sequencing: 62 from U.S. women, 20 each from Italian and Indian women, and 21 from Thai women. RESULTS: Of 151 codons, 18 contained 24 base substitutions, reflecting the overall conserved nature of this region. The HPV-16 E6 region from U. S. women showed considerably more sequence variation than that from European and Asian women. Five patterns common to U.S. and European and Asian samples accounted for 78% of all tumor-associated viruses. The E6 regions known to be involved in p53 binding and degradation are involved with a surprising degree of sequence variation, whereas the carboxy end of the molecule is highly conserved. CONCLUSIONS: The area of greatest sequence variation includes a proposed human leukocyte antigen interaction site. A novel large deletion in one sample results in loss of all functional regions of E6. These findings were analyzed for possible significance with regard to immune selection and functional importance of the carboxy end of the E6 protein.

Laparoscopic accessory splenectomy for recurrent idiopathic thrombocytopenic purpura and hemolytic anemia.

BACKGROUND: Laparoscopic splenectomy is an effective treatment for idiopathic thrombocytopenic purpura (ITP) and hemolytic anemia that has a remission rate of 80-90%. In some patients in whom the disease persists or recurs, a diagnosis of accessory spleen is made. The long-term efficacy of laparoscopic accessory splenectomy is unknown. METHODS: Patients who underwent laparoscopic accessory splenectomy were followed in the outpatient clinic. The perioperative course, blood counts, and need for medical therapy to maintain a normal count were recorded. RESULTS: Eight patients underwent laparoscopic accessory splenectomy. All procedures were completed laparoscopically, and all patients were discharged on the 1st postoperative day. Patients were available for a follow-up period of 15 months range, (3-27). None of the ITP patients achieved a complete remission. Two of them had a partial remission, and five ITP patients are now being treated with chronic corticosteroids to maintain a platelet count of >100,000/ml. CONCLUSION: Laparoscopic accessory splenectomy is associated with a low rate of morbidity and a short hospital stay. Despite its success in removing all residual splenic tissue, most patients will probably not enjoy a complete remission.

Low-dose irradiation as a measure to improve microbial quality of ice cream.

The present study was undertaken to investigate the efficacy of low-dose irradiation to improve the microbial safety of ice cream. Initially three different flavors (vanilla, strawberry and chocolate) of ice cream were exposed, at -72 degrees C, to doses of 1, 2, 5, 10 and 30 kGy to gamma-radiation. Irradiation at 1 kGy resulted in reduction of microbial population by one log cycle, thus meeting the requirement limits prescribed by Bureau of Indian Standards. Pathogens such as Listeria monocytogenes 036, Yersinia enterocoliticta 5692 and Escherichia coli O157:H19, respectively, showed the D10 values 0.38, 0.15 and 0.2 kGy in ice cream at -72 degrees C suggesting the efficacy of low doses (1 kGy) in eliminating them. Sensory evaluation studies of ice cream irradiated at 1, 2, 3 and 5 kGy by a 15 member panel demonstrated that doses higher than 2 kGy irradiation induced off-odour and an aftertaste was evident in vanilla ice cream. A radiation dose of 1 kGy was sufficient to eliminate the natural number of pathogens present in the ice cream. No statistically significant differences were observed in the sensory attributes of all the three flavours of ice cream either unirradiated or exposed to 1 kGy (P < 0.05).

Production of Aspergillus xylanase by lignocellulosic waste fermentation and its application.

Strains of Aspergillus terreus and A. niger, known to produce xylanase with undetectable amounts of cellulase, were studied for xylanase (EC 3.2.1.8) production on various lignocellulosic substrates using solid state fermentation. Of the lignocellulosic substrates used, wheat bran was the best for xylanase production. The effects of various parameters, such as moistening agent, level of initial moisture content, temperature of incubation, inoculum size and incubation time, on xylanase production were studied. The best medium for A. terreus was wheat bran moistened with 1:5 Mandels and Strenberg mineral solution containing 0.1% tryptone, at 35 degrees C, and at inoculum concentration 2x107-2x108 spores 5 g-1 substrate; for A. niger, the best medium was wheat bran moistened with 1:5 Mandels and Strenberg mineral solution containing 0.1% yeast extract, at 35 degrees C, and at an inoculum concentration of 2x107-2x108 spores 5 g-1 substrate. Under these conditions, A. terreus produced 68.9 IU ml-1 of xylanase, and A. niger, 74.5 IU ml-1, after 4 d of incubation. A crude culture filtrate of the two Aspergillus strains was used for the hydrolysis of various lignocellulosic materials. Xylanase preparations from the two strains selectively removed the hemicellulose fraction from all lignocellulosic materials tested.

Irradiation of chewable tobacco mixes for improvement in microbiological quality.

Microbiological quality of chewable tobacco mixes traditionally known as "Gutkha" was studied. The microbiological analysis of 15 samples analyzed revealed high bacterial and fungal counts. The total viable counts were in the range of 1.8 x 10(4) to 7.2 x 10(4) CFU g(-1) and the yeast and mold count from 3.6 x 10(3) to 7.1 x 10(4) CFU g(-1). The proteolytic and lipolytic counts were 9 x 10(2) to 2.6 x 10(3) CFU g(-1) and 2.6 x 10(3) CFU g(-1), on an average, respectively. Lecithinase-positive Staphylococcus aureus was found in 2 of the 15 samples analyzed; the counts were up to 3.4 x 10(3) CFU g(-1). Coliform and Salmonella spp. were found to be absent. Aflatoxins B , B2, and G2 were found to be present in all the samples. These samples were exposed to gamma radiation (60Co) at 1-, 2-, 3-, 5-, 10-, and 25-kGy doses. The decrease in total viable count and fungal count was noticed with increase of radiation dose. The 3-kGy dose was observed to be the sterilization dose for Gutkha. At this dose no survival of organisms was noticed and no revival was observed during postirradiation storage at room temperature for 6 months.

Mobile radiography CQI: an inter-national study.

Mobile or bedside radiography has been and is a staple diagnostic and follow-up tool used readily by the many medical disciplines, such as cardiology, surgery, orthopedics, pediatrics, neonatology, etc. Ironically, in the past a student or the least qualified technologist was sent to perform the bedside exam. Moreover, it was almost expected that poor but acceptable film quality would result or that repeat films were almost always to be taken. Inefficiency with respect to quality of exam, the time the exam takes, or film repeats can be costly. The price of inefficiency is the cost involved in doing things incorrectly or not in the most efficient manner, i.e., incurring inefficiencies instead of operating in an ideal manner. The purpose of this study was to compare the total cost of inefficiently organized, scheduled and performed mobile radiography at three large teaching hospitals in various locations and of diverse patient loads, as a means of determining how best to increase utilization and performance. The study was performed at the 489-bed New England Deaconess Hospital (NEDH), the 644-bed Sentara Norfolk General Hospital (SNGH), and the 1500-bed Rheinische Westfalische Technische Hochschule (RWTH) in Aachen, Germany. Similar standardized study methods were utilized at all three institutions where extended observation of mobile utilization, areas of inefficiency, time wasted per episode and number of episodes per time period were determined. Data were loggedin at three standardized time periods, summated, and then multiplied by technologist hourly pay rate. This sum was extrapolated over 52 weeks to give the total annual cost of inefficiently organized mobile radiography. For NEDH the cost of total inefficiency was $75,453, for SNGH $49,586, while for RWTH it was $9,519. Eighteen areas of inefficiency were identified and grouped, such as lack of spatial cohesiveness and lack of communication leading to film duplication, etc. While inefficiencies in the delivery of hospital based health care are well known, this study attempts to quantify and determine a dollar value for each process found as inefficient. Key inefficiencies were found to be common at large hospitals no matter whether in the United States or Europe. These impairments are responsible for a disproportionate share of overall inefficiency, and their elimination (achievable by simple solutions) would result in drastic cost reductions (ranging from 40-75% at the institutions studied). Thus this study is important in view of spiralling costs, as it is a key component of total quality management (TQM) in radiology and a continuous quality improvement (CQI) tool for mobile radiology specifically.

Preparation, characterization and application of Aspergillus sp. xylanase immobilized on Eudragit S-100.

Aspergillus sp. 5 (strain 5) and Aspergillus sp. 44 (strain 44) produced xylanase (34.3 and 32.7 IU ml-1, respectively) with very low levels of cellulases when grown on 1% wheat bran medium. Xylanase was non-covalently immobilized on Eudragit S-100 for saccharification. The system retained 70 and 80% of strain 5 and strain 44 xylanase activity, respectively. On immobilization, optimum temperature of activity broadened between 50 and 60 degrees C as compared to 50 degrees C in the case of the free enzymes. No significant shift in the pH optima was observed on immobilization. However, immobilization increased enzyme stability mainly by decreasing the temperature sensitivity to the inactivation reaction. The K(m) values increased from 5.6 to 8.3 mg ml-1 for strain 5 xylanase and 7.0 to 9.0 mg ml-1 for strain 44 xylanase. Enzymatic saccharification of xylan and wheat bran was improved on xylanase immobilization. Immobilized xylanase from both the strains produced three times more sugar as compared to free xylanase. In repeated batch saccharification studies immobilized xylanase was recycled three times without loss of enzyme activity.

Adenocarcinoma of bladder.

Forty-eight patients with adenocarcinoma (21 urachal and 27 non-urachal) of the bladder were treated at the Tata Memorial Hospital between 1976 and 1992. The study group consisted of 32 men and 16 women. The urachal tumours were more common in younger patients (mean age: 49 years) than were non-urachal tumours (mean age: 58 years). The overall 5-year survival in this series was 37%. Stage and grade were powerful predictors of outcome. Patients with non-urachal tumours showed an overall survival rate of 29.9% compared with 45.7% in patients with urachal tumours (P= 0.14). Radical cystectomy was the most common treatment modality in patients with non-urachal tumours and yielded an overall 5-year survival of 35%. Patients with urachal tumours were treated with either partial cystectomy or radical cystectomy. The 5-year survival following partial cystectomy was 56.3% compared with 25.9% following a radical cystectomy and the difference between the two was not statistically significant (P = 0.76).

Isolation of wild Xanthomonas strains from agricultural produce, their characterization and potential related to polysaccharide production.

One hundred fifty wild strains of Xanthomonas were isolated on five selective and nonselective media. The comparative effectivity of the five media has been discussed. Fifteen polysaccharide-producing strains shortlisted were identified up to species level. These were studied for polysaccharide production in shake flasks using YM media. The highest final yield of 21.3 g/L of the amount of carbon source supplied has been obtained in the optimum medium in shake-flask experiments from Xanthomonas campestris (ICa-125 strain isolated from cabbage. Rheological properties of the exocellular polysaccharide (EPS) have been compared with standard xanthan. EPS from X. campestris ICa-125 was found to be superior with respect to heat stability and effect of electrolytes as compared to standard xanthan.

A prospective randomized trial of feeding methods in very low birth weight infants.

OBJECTIVE: To test the hypothesis that very low birth weight infants fed by continuous nasogastric gavage (CNG) would achieve full enteral feedings (100 kcal/kg/d) at an earlier postnatal age and have less feeding intolerance (FI) than infants fed by intermittent bolus gavage (IBG). METHODS: Eighty infants were stratified by birth weight (700 to 1000 g and 1001 to 1250 g) and randomized into CNG or IBG feeding groups. CNG infants were comparable with IBG in birth weight, gestational age, sex, race, and day of onset of feeding (5.7 +/- 2.1 days vs 5.6 +/- 2.2 days, respectively). Feedings were given as undiluted Similac Special Care formula (Ross Laboratories, Columbus, OH) via a specific protocol designed for each 50 to 100 g birth weight category. Feedings were advanced isoenergetically by a maximum of 25 mL/kg/d until an endpoint of 100/kcal/kg/d for at least 48 hours was reached. An infant whose feedings were withheld for >12 hours based on predetermined criteria was considered to have an episode of FI. RESULTS: Infants in the CNG group reached full enteral feeding at 17.1 +/- 8.9 days compared with 15.5 +/- 5.5 days in the IBG group; these were not statistically different. Secondary outcome variables such as days to regain birth weight (CNG, 12.6 +/- 5 days vs IBG, 12.5 +/- 3.7 days), days to reach discharge weight of 2040 g (CNG, 60 +/- 13.4 days vs IBG, 62 +/- 13.6 days), and number of episodes of FI were not significantly different between feeding methods. FI was primarily associated with birth weight