PROTECTIVE EFFECT OF ETHANOLIC ROOT EXTRACT OF COMMIPHORA CAUDATA AGAINST DIABETIC-INDUCED RATS IN HIGH-FAT DIET-STREPTOZOTOCIN MODEL

Objective: The present study was to explore the phytochemical analysis and antidiabetic potential of the root of Commiphora caudata in high-fat diet (HFD) streptozotocin-induced diabetic rats. Methods: The ethanolic root extract of C. caudata at a dose of 400 mg/kg and 200 mg/kg was administered to diabetic rats. Glibenclamide (5 mg/kg) was used as standard drug. Results: The data were statistically assessed using one-way ANOVA followed by Dennett’s multiple comparison tests. To unfold the mechanism, we studied all the biochemical parameters glucose, total cholesterol, triglycerides (TG), high-density lipoproteins (HDL), low-density lipoproteins (LDL), and very LDL (VLDL) and histopathological examination of the pancreatic tissue section. The ethanolic extracts of root of C. caudata showed significant reduce of the level of cholesterol, TG, LDL, VLDL, and significant increase in the serum level of HDL at 400 mg/kg rather than 200 mg/kg. Conclusion: Further studies should look into the characterization and isolation of the constituents to know the exact mechanism of hypoglycemic activity. Statistical analyses of this screening method confirm that the proposed method is appropriate and it can be expected to improve basic idea to the researcher who is working in area-like antidiabetic activity

Treatment Of Chronic Kidney Disease Patients With A Supplemented Low Protein Diet And A Supplemented Very Low Protein Diet

The primary results of the Modification of Diet in Renal Disease were inconclusive and did confuse a lot of physicians about the dietary approach to CKD management. The study design was flawed and thus compromised the results and conclusions. Re-analysis of the MDRD study however clearly showed the benefits of dietary protein restriction and also more importantly an additional benefit by ketoanalogue supplementation in delaying progression of CKD. Despite the obvious benefits of protein restriction, concern has been raised recently especially patients on very low dietary protein (very-low-protein diets; VLPDs), which could lead to deterioration in the nutritional status of CKD patients. To address this particular issue of whether a sVLPD diet induces malnutrition the present study has been taken up 132adult patients with Stage 3 to Stage 5 (Predialysis) were initiated on a protein restricted ketoanalogue supplemented diet after informed consent and the necessary Institutional Ethics Committee approvals. Based on their affordability, 92 patients randomly were assigned to the sLPD group whereby they received 0.6G/Kg BW of dietary proteins supplemented by ketoanalogues at a dosage of one tablet per 10Kg body weight. 40 patients received 0.3G/Kg BW supplemented by ketoanalogues at a dose of one tablet per 5Kg body weight. Renolog® tablets manufactured by La Renon Healthcare Ltd, Ahmebabad, India were prescribed as the ketoanalogue supplements. Renal, Metabolic, Nutritional parameters and Anthropometric analysis were done in both groups at the start of the study and at the end of 6 months of follow up. The mean blood urea in the SLPD group showed a decrease from 81.17+_ 00mg/dl to 74.45+_30.75mg/dl (p< 0.05) and in the SVLPD from 78.35+_00mg/dl to 66.50+_34.50mg/dl (p>0.05) at the end of six months indicating an improvement in renal function . The serum creatinine also showed a decrease from 3.52+_00mg/dl to 3.30 +_1.63mg/dl(p>0.05) in the SLPD group and a decrease from 3.74+_00mg/dl to 3.55+_1.67mg/dl(p>0.05) in the SVLPD group though not statistically significant. The eGFR showed improvement from 26.76+_00ml/min to 30.75+_17.31ml/min (p<0.05) at end of six months in the SLPD group and an increase from 23.62+_00ml/min to 26.35+_10.58ml/min(p>0.05) in the SVLPD group. Serum albumin increased from 3.85+_00gm/dl to 4.00+_0.56gm/dl (p<0.05) in the SLPD group and an increase from 4.03+_00gm/dl to 4.07+_0.47gm/dl in the SVLPD group indicating an improvement in nutrition in SVLPD group (p>0.05) . Blood hemoglobin increased from 11.18+_2.02gm/dl to 11.48+_2.14gm/dl in the SLPD group and an increase from 11.35+_0.96gm/dl to 13.22+_1.03gm/dl in the SVLPD group. Combined analysis of both the study groups together(SLPD +SVLPD) showed a statistically significant decrease in blood urea from 80.32+_0.0 mg/dl to 73.70+_31.81mg/dl(p<0.05), decrease in serum creatinine from 3.59+_0.0mg/dl to 3.38+_1.64mg/dl (0>0.05) and increase in eGFR from 25.82+_ 0.0ml/min to 29.42+_ 15.67ml/min(<0.05) at the end of six months of therapy which was statistically significant indicating an improvement in renal function. The serum albumin increased from 3.91+_0.0gm/dl to 4.02+_0.53gm/dl (p<0.05) indicating a statistically significant improvement in nutrition. The protein restricted ketoanalogue treated patients in this large series showed significant improvement in their renal function, metabolic status and their extensively investigated nutritional parameters over a period of 6 months. The key here is to use the right dosage of the ketoanalogue supplements in addition to ensuring strict compliance of dietary restrictions. It is strongly recommended that ketoanalogues be routinely used in the conservative management of CKD

Evaluation of the CERES-Rice version 3.0 model for the climate conditions of the state of Kerala, India

The CERES-Rice version 3.0 crop growth simulation model was calibrated and evaluated for the agroclimatic conditions of the state of Kerala in India. Genetic coefficients were developed for the rice crop variety Jaya and used for the model evaluation studies. In four experiments using different transplanting dates during the virippu season (June to September) under rainfed conditions (i.e. no irrigation), the flowering date was predicted within an error of four days and date of crop maturity within an error of two days. The model was found to predict the phenological events of the crop fairly well. The grain yield predicted by the model was within an error of 3 for all the transplanting dates, but the straw yield prediction was within an error of 27. The high accuracy of the grain yield prediction showed the ability of the model to simulate the growth of the crop in the agroclimatic conditions of Kerala. It can be concluded from this study that the model can be used for making various strategic and tactical decisions related to agricultural planning in the state

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

Transesterification of PHA to Oligomers Covalently Bonded with (Bio)Active Compounds Containing Either Carboxyl or Hydroxyl Functionalities

© 2015 The Authors. Published by Public Library of Science. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1371/journal.pone.0120149This manuscript presents the synthesis and structural characterisation of novel biodegradable polymeric controlled-release systems of pesticides with potentially higher resistance to weather conditions in comparison to conventional forms of pesticides. Two methods for the preparation of pesticide-oligomer conjugates using the transesterification reaction were developed. The first method of obtaining conjugates, which consist of bioactive compounds with the carboxyl group and polyhydroxyalkanoates (PHAs) oligomers, is "one-pot" transesterification. In the second method, conjugates of bioactive compounds with hydroxyl group and polyhydroxyalkanoates oligomers were obtained in two-step method, through cyclic poly(3-hydroxybutyrate) oligomers. The obtained pesticide-PHA conjugates were comprehensively characterised using GPC, 1H NMR and mass spectrometry techniques. The structural characterisation of the obtained products at the molecular level with the aid of mass spectrometry confirmed that both of the synthetic strategies employed led to the formation of conjugates in which selected pesticides were covalently bonded to PHA oligomers via a hydrolysable ester bond

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone