103 research outputs found

    Gastroprotective activity and mechanisms of action of Bauhinia purpurea Linn (Leguminoseae) leaf methanol extract

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    Purpose: To determine the gastroprotective activity and mechanisms of protection of the methanol extract of Bauhinia purpurea leaves (MEBP) using ethanol-induced gastric ulcer model.Methods: Male Sprague Dawley rats (n = 6) were administered orally with 10 % DMSO, 100 mg/kg ranitidine or MEBP (50, 250 and 500 mg / kg) daily for 7 consecutive days prior to subjection to the ethanol-induced gastric ulcer assay. The mechanisms of gastroprotection were determined based on: i) antisecretory activity via pylorus ligation assay; ii) the role of nitric oxide (NO) and sulfhydryl group via pre-treatment of MEBP-treated rats with the respective N-nitro-L-arginine methyl ester (L-NAME) or carbenoxolone (CBX) followed by the ethanol-induced assay; and iii) antioxidant activity using superoxide anion radical scavenging assay and, oxygen radical absorbance capacity (ORAC) assay. Ranitidine (100 mg / kg) was used as the reference drug. .Results: MEBP exhibited a significant (p < 0.05) and dose-dependent gastroprotective activity against ethanol-induced gastric ulcer with ulcer formation ranging between 0 and 74 % (indicated by decrease in ulcer area from 21.3 to 5.5 mm2). The macroscopic observation was in line with the microscopic findings and further supported by the histological scores suggesting the antiulcer potential of MEBP. MEBP also significantly (p < 0.05) reduced volume gastric juice, as well as its free and total acidity while increasing its pH. Moreover, this activity was significantly (p < 0.05) modulated in the presence ofsulfhydryl group, but not NO. The extract also exhibited significant (p < 0.05) antioxidant activity.Conclusion: MEBP exerts gastroprotective activity partly via its antisecretory and antioxidant activities, as well as by modulation of sulfhydryl group, but not NO action.Keywords: Bauhinia purpurea, Gastroprotective activity, Gastric ulcer, Sulfhydryl group, Anti-secretory activity, Antioxidan

    Sequence‐Based Saudi Population Data for The SE33 Locus

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    A set of 87 reference samples collected from the population of Saudi Arabia were sequenced using the ForenSeqTM DNA Signature Prep Kit on a MiSeq FGxTM. The FASTQ files contain the sequences of the SE33 STR, but are not reported by the ForenSeqTM Universal Analysis Software (UAS). The STRait Razor software was used to recover and to report SE33 sequence‐based data for the Saudi population. Ninety-six sequence-based alleles were recovered, most of which had previously reported motif patterns. Two unreported motif patterns found in three alleles and seven novel allele sequences were reported. We also reported a single discordance between the sequence-based data and the CE data that was due to the presence of a common TTTT deletion. SE33 had 130% more sequence-based alleles; the highest number of observed sequence variants were in alleles 27.2 and 30.2, which each had 7 sequence variants. The statistical parameters emphasize the usefulness of using the sequence-based data

    The identification of informative genes from multiple datasets with increasing complexity

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    Background In microarray data analysis, factors such as data quality, biological variation, and the increasingly multi-layered nature of more complex biological systems complicates the modelling of regulatory networks that can represent and capture the interactions among genes. We believe that the use of multiple datasets derived from related biological systems leads to more robust models. Therefore, we developed a novel framework for modelling regulatory networks that involves training and evaluation on independent datasets. Our approach includes the following steps: (1) ordering the datasets based on their level of noise and informativeness; (2) selection of a Bayesian classifier with an appropriate level of complexity by evaluation of predictive performance on independent data sets; (3) comparing the different gene selections and the influence of increasing the model complexity; (4) functional analysis of the informative genes. Results In this paper, we identify the most appropriate model complexity using cross-validation and independent test set validation for predicting gene expression in three published datasets related to myogenesis and muscle differentiation. Furthermore, we demonstrate that models trained on simpler datasets can be used to identify interactions among genes and select the most informative. We also show that these models can explain the myogenesis-related genes (genes of interest) significantly better than others (P < 0.004) since the improvement in their rankings is much more pronounced. Finally, after further evaluating our results on synthetic datasets, we show that our approach outperforms a concordance method by Lai et al. in identifying informative genes from multiple datasets with increasing complexity whilst additionally modelling the interaction between genes. Conclusions We show that Bayesian networks derived from simpler controlled systems have better performance than those trained on datasets from more complex biological systems. Further, we present that highly predictive and consistent genes, from the pool of differentially expressed genes, across independent datasets are more likely to be fundamentally involved in the biological process under study. We conclude that networks trained on simpler controlled systems, such as in vitro experiments, can be used to model and capture interactions among genes in more complex datasets, such as in vivo experiments, where these interactions would otherwise be concealed by a multitude of other ongoing events

    The silent HIV epidemic among pregnant women within rural Northern Tanzania

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    BACKGROUND: Many national antenatal clinics (ANC) based HIV surveillance systems in sub-Saharan Africa have limited coverage of remote rural sites, a weakness that compromises adequate estimation, monitoring and development of effective preventive and care programmes. To address this void in rural Manyara and Singida within Northern Tanzania, we conducted antenatal clinic-based sentinel surveillance. METHODS: We consecutively enrolled 1377 counselled and consenting pregnant women attending ANC clinics for the first time during the current pregnancy. The study was conducted in six antenatal clinics, within three divisions of rural Manyara and Singida regions in 2003/2004. Interviews were conducted and blood samples for routine purposes were collected and tested for anti-HIV IgG antibody anonymously, using Bionor HIV-1 & 2 assay (®). RESULTS: Among enrolees, 94% (1296/1377) participated fully. The overall prevalence of HIV was 2.0% (95%CI: 1.34–2.97). The highest HIV prevalence was among women aged between 15–19 years in both rural and remote rural populations. The odds of HIV infection was 4.3 (95%CI: 1.42–12.77) times among women reporting more than one lifetime sexual partners compared with those with one partner. HIV infection was associated with history of genital sores or foul smelling discharge, OR 6.8 (95%CI: 2.78–16.66) and age at first pregnancy (2.5 times higher likelihood of infection if before the age of 18 years versus at a later age). CONCLUSION: Including rural remote sites, as part of the national ANC routine surveillance, is crucial in order to discover imminent silent epidemics such as the one described in this paper. Scaling up HIV prevention efforts is mandatory to prevent the imminent escalation of the HIV epidemic highly associated with a history of sexually transmitted infections (STIs), multiple sexual partners and pregnancies at a younger age. Ignorance of relevant knowledge and low utilisation of condoms underscores the urgency for large-scale preventive efforts. Research to capture a wider representation of the risk factors in the general population should be a priority to enable further customised HIV prevention efforts

    Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

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    Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

    Emerging Strategies for Healthy Urban Governance

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    Urban health promotion is not simply a matter of the right interventions, or even the necessary resources. Urban (and indeed global) health depends to an important extent on governance, the institutions and processes through which societies manage the course of events. This paper describes the concept of governance, distinguishing between reforms aimed at improving how government works and innovations that more fundamentally reinvent governance by developing new institutions and processes of local stakeholder control. The paper highlights strategies urban governors can use to maximize their influence on the national and international decisions that structure urban life. It concludes with some observations on the limitations of local governance strategies and the importance of establishing a “virtuous circuit” of governance through which urban dwellers play a greater role in the formation and implementation of policy at the national and global levels

    Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection

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    Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis and meningitis. Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered and sustained by circulating pneumolysin (PLY). Using a mouse model of invasive pneumococcal disease (IPD), we demonstrate that wild type PLY-expressing pneumococci but not PLY-deficient mutants induced elevation of circulating cardiac troponins (cTns), well-recognized biomarkers of cardiac injury. Furthermore, elevated cTn levels linearly correlated with pneumococcal blood counts (r=0.688, p=0.001) and levels were significantly higher in non-surviving than in surviving mice. These cTn levels were significantly reduced by administration of PLY-sequestering liposomes. Intravenous injection of purified PLY, but not a non-pore forming mutant (PdB), induced substantial increase in cardiac troponins to suggest that the pore-forming activity of circulating PLY is essential for myocardial injury in vivo. Purified PLY and PLY-expressing pneumococci also caused myocardial inflammatory changes but apoptosis was not detected. Exposure of cultured cardiomyocytes to PLY-expressing pneumococci caused dose-dependent cardiomyocyte contractile dysfunction and death, which was exacerbated by further PLY release following antibiotic treatment. We found that high PLY doses induced extensive cardiomyocyte lysis, but more interestingly, sub-lytic PLY concentrations triggered profound calcium influx and overload with subsequent membrane depolarization and progressive reduction in intracellular calcium transient amplitude, a key determinant of contractile force. This was coupled to activation of signalling pathways commonly associated with cardiac dysfunction in clinical and experimental sepsis and ultimately resulted in depressed cardiomyocyte contractile performance along with rhythm disturbance. Our study proposes a detailed molecular mechanism of pneumococcal toxin-induced cardiac injury and highlights the major translational potential of targeting circulating PLY to protect against cardiac complications during pneumococcal infections

    Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality

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    Background and purpose: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P&lt;0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P&lt;0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT

    Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

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    Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics
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