DEVELOPMENT OF CARBON TETRACHLORIDE-INDUCED CHRONIC HEPATOTOXICITY MODEL IN RATS AND ITS APPLICATION IN EVALUATION OF HEPATOPROTECTIVE ACTIVITY OF SILYMARIN

Objective: The objective of the present work is to develop carbon tetrachloride (CCl4)-induced chronic hepatotoxicity model in rats and its applicationin evaluation of hepatoprotective activity of silymarin.Methods: Animals were divided into four groups. Three groups were the disease induction group and 4th was the treatment group. In disease inductiongroups, chronic liver injury was induced by administration of CCl4 through intraperitoneal route (1 ml/kg) for 7-8 weeks. For treatment Group, 1 mlsilymarin suspension (orally) and CCl4 was given for 7-8 weeks. During disease induction and treatment period (7-8 weeks), blood samples werecollected and serum was separated which in turn used to analyze liver function tests such as serum glutamate oxaloacetate transaminase (SGOT),serum glutamate pyruvate transaminase (SGPT), alkaline phosphate (ALP), direct bilirubin, total protein (TP), and albumin (Alb) levels. Along withliver functional tests, tests to check cholesterol, glucose, and malondialdehyde (MDA) were also performed. Liver fibrosis and cirrhosis was quantifiedby histopathological studies of small portion of the excised liver. Model was validated by repetition of the experiment. Intermediate dissection wascarried out to measure an extent of liver damage.Result: Serum SGOT, SGPT, ALP, and direct bilirubin were found to be significantly higher in CCl4 intoxicated rats. TP and Alb were decreased, andMDA was found to be significantly higher in CCl4 intoxicated rats, which is the main end product of lipid peroxidation. Whereas in the treatment groupsilymarin improved the liver functions in CCl4 toxicated drug.Conclusion: We conclude that protein oxidation may play a role in the pathogenesis of CCl4 induced liver injury. The accumulation of oxidized proteinsmay be an early indication of CCl4 induced liver damage and silymarin found to be effective in liver injury by inhibiting protein oxidation

Improving Navigation for Street Data Using Mobile Augmented Reality

ABSTRAC

Permanent Nonselective His Bundle Pacing in an Adult with L-Transposition of the Great Arteries and Complete AV Block

We report the placement of a permanent transvenous nonselective His bundle pacing lead in conjunction with a transvenous pacemaker/implantable cardioverter-defibrillator in an adult with Levo-Transposition of the Great Arteries (L-TGA) and a stenotic coronary sinus (CS) ostium, which would not accommodate a transvenous left ventricular (LV) pacing lead. Nonselective His bundle pacing provided a nearly identical ventricular activation pattern in this previously unpaced patient. Many L-TGA patients will have an eventual need for permanent pacing and, given the challenges of CS cannulation, His bundle pacing may represent a preferred modality rather than pure morphologic LV pacing or surgical systemic ventricular lead placement to achieve optimal electrical synchrony

Exploring the cognitive processes of both Arabic and English-speaking patients when completing the brief pain inventory: A qualitative study

Background: Brief Pain Inventory (BPI) is one of the most commonly used self-initiated questionnaire for people with chronic pain. Although the questionnaire has been translated into multiple different languages and tested for its inter-tester reliability, no study has currently explored the differences in interpretation of this questionnaire between non-English speakers as compared to English-speakers. Purpose: Using the Arabic-language group as the comparator, this study explored the interpretation of the English and Arabic language Brief Pain Inventory (BPI) among participants living with chronic neuromusculoskeletal pain from Arabic- and English-speaking backgrounds. Methods: This qualitative study utilises the Think Aloud method to explore the differences in the interpretation of the BPI between two language groups. Consecutive consenting adults attending a tertiary pain clinic for management of a chronic neuromusculoskeletal pain condition and self-identifying with a native English-speaking (n = 15) or Arabic-speaking (n = 15) background were included. Structured interviews using the think-aloud method were conducted, audio-recorded and analysed using coding and thematic analysis. Results: Interpretation errors across three or more questions were recorded for all Arabic-speaking participants and two English-speaking participants. Three themes characterised appraisals of pain and interpretation of the BPI across the two cohorts: 1) pain constancy vs. variability, 2) the ability-disability spectrum and 3) variance in expression of pain. Conclusion: Cross-cultural differences in the appraisal of pain influenced participants' interpretation of the BPI. The cultural influences on conceptualisation of pain need to be considered when using the BPI across different cultures

Frequency and distribution of ABO and Rh blood groups among blood donors in tertiary care hospital of South Gujarat, India

Background: Since it was discovered by Karl Landsteiner, the ABO blood group system is the most important blood group system in Transfusion Medicine. The blood group systems are also very important in population genetic studies, researching population migration patterns as well as resolving certain medico-legal issues, particularly disputed parentage. This study was carried out with an objective to provide data regarding gene frequency and distribution of ABO and Rh blood groups among blood donors in South Gujarat, India.Methods: Data of 40732 blood donors were retrospectively collected and analyzed regarding ABO and Rh blood groups from May-2011 to April-2016 and reported in simple numbers and percentage. Blood group of the blood donors was determined by forward and reverse methods with the help of commercially available standard monoclonal antisera by test tube and column agglutination techniques in required cases.Results: The most common blood group among donors was B (34.43%) followed by O (32.26%), A (24.35%), while the least prevalent blood group was AB (8.94%). Rh positivity among donors was (95.12%). Rests were Rh Negative (4.87%). The estimated gene frequencies were 0.1844 for IA (p), 0.2477 for IB (q) and 0.5679 for IO (r).Conclusions: The most common blood group in donors was B positive and least common was AB negative

Prevalence and trends of transfusion transmitted infections among blood donors of blood bank attached to government hospital of South Gujarat, India

Background: Though the blood transfusion is lifesaving, it is never risk free and carries potential risk for transfusion transmitted infections (TTIs).The objective of present study is to assess the prevalence and trend of TTIs among blood donors in the blood bank attached to tertiary level government hospital and its comparison with national data and other studies of different regions.Methods: Retrospective cross-sectional study was done including healthy blood donor of 18-65 years from May 2011 to April 2016. TTIs testing were done with 3rd generation ELISA for HIV, HBV and HCV and HIV testing was also done with 4th generation ELISA from the year 2014 onwards. Syphilis screening was done either by RPR, TPHA strip test or ELISA and Malaria parasite was tested either by peripheral smear or rapid test.Results: From 40971 donors in study, 550 (1.34%) donors were sero-reactive from which 400 (0.98%) donors were reactive for HBV, 67 (0.16%) were for syphilis, 40 (0.098%) were for HCV, 33 (0.081%) were reactive for HIV and 10 (0.024%) were malaria positive. During the study period four donors showed co infection for HIV and HBV. Most common age group to be sero reactive in the present study is 21-30 years of age (43.09% of total).Conclusions: Prevalence of TTIs in the present study was lower as compare to other studies of the India. The reasons behind this finding may be better pre-donation counseling, better life style, higher proportion of voluntary blood donation (> 99%) and high pre-donation deferral rate (11.17%)

Healthcare Utilization and Quality of Life Improvement after Ablation for Paroxysmal AF in Younger and Older Patients

Background Atrial fibrillation (AF) prevalence increases significantly with age. Little is known about the effect of AF ablation on quality of life and healthcare utilization in the elderly. The objective of this study was to quantify the healthcare utilization and quality of life benefits of catheter ablation for AF, for patients ≥65 years compared to patients <65 years. Methods Two multicenter U.S. registry studies enrolled patients with paroxysmal AF. Baseline characteristics and acute outcomes were collected for 736 patients receiving catheter ablation with the Navistar® ThermoCool® SF Catheter (Biosense Webster, Inc., Diamond Bar, CA, USA). Healthcare utilization and quality of life outcomes were collected through 1 year postablation for 508 patients. Results The rates of acute pulmonary vein isolation were high and similar between patients ≥65 years and <65 years (97.5% vs 95.8%, P = 0.2130). Length of stay for the index procedure was similar between age groups with 82.2% of the older group and 83.2% of the younger group having one-day hospitalization. Disease-specific quality of life instrument scores improved significantly and similarly for older and younger patients at 1 year postablation, compared to baseline. AF-related hospitalizations and emergency department visits were similar or lower in older patients compared to younger patients, as reported at 1 year postablation. Conclusion For older patients undergoing catheter ablation for paroxysmal AF, healthcare utilization parameters were lower or not significantly different than for younger patients, and quality of life outcomes were similarly improved. These findings support the use of catheter ablation as a treatment option in older patients with paroxysmal AF

Preclinical Pharmacokinetic Evaluation to Facilitate Repurposing of Tyrosine Kinase Inhibitors Nilotinib and Imatinib as Antiviral Agents

Background Several tyrosine kinase inhibitors (TKIs) developed as anti-cancer drugs, also have anti-viral activity due to their ability to disrupt productive replication and dissemination in infected cells. Consequently, such drugs are attractive candidates for “repurposing” as anti-viral agents. However, clinical evaluation of therapeutics against infectious agents associated with high mortality, but low or infrequent incidence, is often unfeasible. The United States Food and Drug Administration formulated the “Animal Rule” to facilitate use of validated animal models for conducting anti-viral efficacy studies. Methods To enable such efficacy studies of two clinically approved TKIs, nilotinib, and imatinib, we first conducted comprehensive pharmacokinetic (PK) studies in relevant rodent and non-rodent animal models. PK of these agents following intravenous and oral dosing were evaluated in C57BL/6 mice, prairie dogs, guinea pigs and Cynomolgus monkeys. Plasma samples were analyzed using an LC-MS/MS method. Secondarily, we evaluated the utility of allometry-based inter-species scaling derived from previously published data to predict the PK parameters, systemic clearance (CL) and the steady state volume of distribution (Vss) of these two drugs in prairie dogs, an animal model not tested thus far. Results Marked inter-species variability in PK parameters and resulting oral bioavailability was observed. In general, elimination half-lives of these agents in mice and guinea pigs were much shorter (1–3 h) relative to those in larger species such as prairie dogs and monkeys. The longer nilotinib elimination half-life in prairie dogs (i.v., 6.5 h and oral, 7.5 h), facilitated multiple dosing PK and safety assessment. The allometry-based predicted values of the Vss and CL were within 2.0 and 2.5-fold, respectively, of the observed values. Conclusions Our results suggest that prairie dogs and monkeys may be suitable rodent and non-rodent species to perform further efficacy testing of these TKIs against orthopoxvirus infections. The use of rodent models such as C57BL/6 mice and guinea pigs for assessing pre-clinical anti-viral efficacy of these two TKIs may be limited due to short elimination and/or low oral bioavailability. Allometry-based correlations, derived from existing literature data, may provide initial estimates, which may serve as a useful guide for pre-clinical PK studies in untested animal models

Childhood intussusception in Uzbekistan: Analysis of retrospective surveillance data

<p>Abstract</p> <p>Background</p> <p>Estimates of baseline incidence of childhood intussusception could help safety monitoring after the introduction of rotavirus vaccines. We studied the incidence of intussusception in Uzbekistan, a GAVI-fund eligible state in Central Asia.</p> <p>Methods</p> <p>We retrospectively reviewed intussusception cases in children <2 years of age treated during 2004-2008 at 15 hospitals in the Bukhara region of Uzbekistan. Demographic and clinical data as well as information on diagnostic and treatment practices were obtained from hospital records. We categorized cases using the Brighton collaboration clinical case definition and calculated the national incidence rate.</p> <p>Results</p> <p>Over a 5-year study period, 67 confirmed cases were identified, of which 67% were boys. The median age was 12 months, and no seasonal trend in the distribution of cases was observed. The diagnostic methods used included abdominal radiography (87%) and ultrasonography (57%). Intussusception reduction by air enema was successful in 33 (49%) patients and 34 (50%) cases underwent surgery. A total of 4 deaths occurred, including 3 deaths in infants aged 0-6 months. The median length of hospital stay was 7.3 (range 0-37) days. The incidence of intussusception is estimated at 23 (95% CI 13.6-32.4) cases per 100,000 child-years, corresponding to approximately 237 cases annually.</p> <p>Conclusions</p> <p>This is the first study to estimate the incidence of childhood intussusception prior to the introduction of the rotavirus vaccination in Uzbekistan. A prospective surveillance system using a standardized case definition is needed in order to better examine the occurrence of intussusception in developing countries.</p

Whole-genome sequencing identifies emergence of a quinolone resistance mutation in a case of Stenotrophomonas maltophilia bacteremia

Whole-genome sequences for Stenotrophomonas maltophilia serial isolates from a bacteremic patient before and after development of levofloxacin resistance were assembled de novo and differed by one single-nucleotide variant in smeT, a repressor for multidrug efflux operon smeDEF. Along with sequenced isolates from five contemporaneous cases, they displayed considerable diversity compared against all published complete genomes. Whole-genome sequencing and complete assembly can conclusively identify resistance mechanisms emerging in S. maltophilia strains during clinical therapy