Cytoprotective and antioxidant effects of the methanol extract of Eremomastax Speciosa in rats

Background: Ethno-botanical information shows that Eremomastax speciosa is used in the traditional management of various stomach complaints including gastro-duodenal ulcers.Materials and Methods: In this study, we tested the cytoprotective potential of the whole plant methanol extract (100-200 mg/kg, p.o), against HCl/ethanol, absolute ethanol, cold/restraint stress rats, and pylorus legated rats pre-treated with indomethacin. The effects of the extract on gastric lesion inhibition, the volume of gastric juice, gastric pH, gastric acid output, mucus production and gastric peptic activity were recorded. Oxidative stress parameters were measured in blood and gastric tissue samples obtained from the animals in all the models tested.Results: The extract significantly (p<0.05), reduced the formation of cold/restraint ulcers by (31-60%, inhibition), completely inhibited (100%) the formation of lesions induced by HCl/ethanol at the highest dose, but was less effective against absolute ethanol (22-46% inhibition). The extract (200 mg/kg), significantly reduced lesion formation (P<0.01), gastric acidity (P<0.01), and volume of gastric secretions (P<0.05), in the indomethacin/pylorus ligation model, and did not affect the activity of pepsin in gastric juice. Blood concentrations of antioxidant enzymes (catalase, SOD and GSH), increased significantly and MDA concentrations decreased in all models tested.Conclusion: Cytoprotection by E. speciosa methanol extract was attributed to its ability to reduce acid secretion, and to enhance mucosal defence and in vivo antioxidant status.Key words: Eremomastax speciosa, cytoprotection, gastric ulcers, antioxidant statu

A comparison of intrauterine haemopoietic cell transplantation and lentiviral gene transfer for the correction of severe β-thalassaemia in a HbbTh3/+ murine model

Major haemoglobinopathies place tremendous strain on global resources. Intrauterine haemopoietic cell (IUHCT) and gene (IUGT) therapies can potentially reduce perinatal morbidities with greater efficacy than postnatal therapy alone. We performed both procedures in the thalassaemic HbbTh3/+ murine model. Intraperitoneal delivery of coisogenic cells at E13-14 produced dose-dependent chimerism. High-dose adult bone marrow (BM) cells maintained 0.2-3.1% chimerism over ~24 weeks and treated heterozygotes demonstrated higher chimerism than wild-type pups (1.6 vs. 0.7%). Fetal liver cells produced higher chimerism compared to adult BM when transplanted at the same doses, maintaining 1.8-2.4% chimerism over ~32 weeks. We boosted transplanted mice postnatally with adult BM cells following busulfan conditioning. Engraftment was maintained at >1% only in recipients which were chimeric prior to boosting. IUHCT-treated non-chimeras and non-IUHCT mice showed micro- or no chimerism. Additional fludarabine treatment produced higher chimerism than busulfan alone. Engraftment was more effective following higher starting chimerism prior to boosting and in heterozygotes. Chimeric heterozygotes expressed 2.2-15.1% donor cells with eventual decline at 24 weeks (vs. <1% in non-chimeras) and demonstrated improved haematological indices and smaller spleens compared to untreated heterozygotes. Intravenous delivery of GLOBE lentiviral-vector expressing HBB (human β-globin) resulted in vector concentration of 0.001-0.6 copies/cell. Most haematological indices were higher in treated than untreated heterozygotes including haemoglobin and mean corpuscular volume, though still lower than in wild-types. Thus both direct IUGT and IUHCT strategies can be used to achieve haematological improvement but require further dose optimisation. IUHCT will be useful combined with postnatal transplantation to further enhance engraftment

The 28-day mortality prediction in sepsis patients using static lactate concentration and early lactate clearance: an observational study.

Sepsis causes high mortality and morbidity. Static lactate concentration and early lactate clearance are cited to be a predictor for sepsis survival. This study examined the clinical utility of static lactate concentration and early lactate clearance within the first six hours of admission in Emergency Department (ED) to predict 28-day mortality rate in sepsis patients. Patients who presented with sepsis, severe sepsis or septic shock and admitted to ED of Universiti Kebangsaan Malaysia Medical Centre were recruited. Blood lactate concentrations were measured upon admission (H0), at 1st hour (H1) and 6th hour (H6), respectively. Either standard treatment of sepsis or early goal directed therapy was initiated according to sepsis severity. A follow-up report was conducted at 28 days via telephone call, e-mail or case notes. Patients were later classified into survivor and non-survivor as final outcome. Static lactate concentration appeared to be significantly higher for non-survivor as compared to the survival group at H0, H1 and H6 (p<0.05). The lactate clearance trend reflects no relationship between early lactate clearance and 28-day mortality. Static lactate concentration showed a superior predictor for sepsis over early lactate clearance. Although early lactate clearance was unable to prove its ability to predict 28-day mortality, our findings suggest it can be a useful tool to gauge the resuscitation outcome

Cost analysis of psoriasis treatment modalities in Malaysian public hospitals

Psoriasis imposes a great economic burden as a result of higher expenditures for different interventions, diagnostic procedures, pharmaceuticals and loss of productivity. Less is known about the economic impact of psoriasis treatment in Asean region. The aim of this research was to calculate the costs associated with four psoriasis treatment modalities. A prospective cohort study was conducted in five hospitals involving 91 moderate to severe psoriasis patients. Costs were calculated from the societal perspective using the principle of Step Down and Activity Based Costing (ABC) within a six (6) months follow-up duration. The components of the costs borne by the provider were inpatient cost, cost of medication, laboratory investigation and radiology. Patient’s cost included out of pocket expenses, travelling cost and loss of productivity. Cost per patient per day was RM1,105.24 (inpatient) (US$315.94) and RM298.02 (outpatient) (US$85.19). Medication accounted for almost 90% (RM457,014.00) (US$130 638.45) of the total provider cost. Meanwhile, loss of productivity represented 84$47,862.80) of the total patient’s cost. Biologic treatment exhibited the highest cost which was RM342,377.00 (US$97,869.21), followed by systemic treatment (RM105,607.00) (US$30,187.99), topical treatment (RM38,280.00) (US$10,942.42) and topical phototherapy treatment (RM21,824.00) (US$6,238.44). Understanding the relationship between direct and indirect costs from both perspectives is important to accurately identify and evaluate effective treatment for psoriasis

The Use of International Classification of Diseases Codes to Identify Patients with Pancreatitis: A Systematic Review and Meta-analysis of Diagnostic Accuracy Studies.

BACKGROUND: Hospital discharge codes are increasingly used in gastroenterology research, but their accuracy in the setting of acute pancreatitis (AP) and chronic pancreatitis (CP), one of the most frequent digestive diseases, has never been assessed systematically. The aim was to conduct a systematic literature review and determine accuracy of diagnostic codes for AP and CP, as well as the effect of covariates. METHODS: Three databases (Pubmed, EMBASE and Scopus) were searched by two independent reviewers for relevant studies that used International Classification of Disease (ICD) codes. Summary estimates of sensitivity, specificity and positive predictive value were obtained from bivariate random-effects regression models. Sensitivity and subgroup analyses according to recurrence of AP and age of the study population were performed. RESULTS: A total of 24 cohorts encompassing 18,106 patients were included. The pooled estimates of sensitivity and specificity of ICD codes for AP were 0.85 and 0.96, respectively. The pooled estimates of sensitivity and specificity of ICD codes for CP were 0.75 and 0.94, respectively. The positive predictive value of ICD codes was 0.71 for either AP or CP. It increased to 0.78 when applied to incident episode of AP only. The positive predictive value decreased to 0.68 when the ICD codes were applied to paediatric patients. CONCLUSION: Nearly three out of ten patients are misidentified as having either AP or CP with the indiscriminate use of ICD codes. Limiting the use of ICD codes to adult patients with incident episode of AP may improve identification of patients with pancreatitis in administrative databases.COSMOS (Clinical and epidemiOlogical inveStigations in Metabolism, nutritiOn, and pancreatic diseaseS (COSMOS) program) is supported in part by the Royal Society of New Zealand (Rutherford Discovery Fellowship to Associate Professor Petrov

Perioperative analgesic modality and effectiveness in paediatric patients who have undergone common major urology surgery - a two-year retrospective study

Perioperative paediatric major urology surgery pain management remains challenging. These surgeries require general anaesthesia (GA) combined with either regional analgesia technique or systemic morphine infusion for optimal pain relief. We aimed to compare and evaluate the effectiveness of both analgesic techniques. This single centre retrospective descriptive study involved 88 patients, aged 3 months to 12 years old with American Society of Anaesthesiologists (ASA) I or II status, who underwent major urology surgery under GA. Group A patients received perioperative systemic morphine while Group B received regional anaesthesia blocks (continuous caudal epidural infusion, single-shot caudal blocks or single-shot erector spinae blocks). We measured requirements of perioperative rescue intravenous (IV) fentanyl, pain scores using Face, Leg, Activity, Cry, Consolability (FLACC) scale, perioperative non-opioid IV analgesia usage and associated complications. Intraoperative rescue fentanyl in both groups was comparable. Intraoperative non-opioid analgesia and postoperative rescue fentanyl requirement were significantly higher in Group A compared to Group B (p<0.001). Median FLACC scores in Group A were higher than Group B (p<0.001) for first 12 hours post-surgery. Commonest complications in Group A was vomiting (38.6%) and peri-catheter leak in Group B (6.81%). Regional anaesthesia technique is superior to systemic morphine in providing analgesia in the first 12 hours post paediatric major urology surgery and is devoid of opioid side effects

Comparative Study of Inference Methods for Bayesian Nonnegative Matrix Factorisation

In this paper, we study the trade-offs of different inference approaches for Bayesian matrix factorisation methods, which are commonly used for predicting missing values, and for finding patterns in the data. In particular, we consider Bayesian nonnegative variants of matrix factorisation and tri-factorisation, and compare non-probabilistic inference, Gibbs sampling, variational Bayesian inference, and a maximum-a-posteriori approach. The variational approach is new for the Bayesian nonnegative models. We compare their convergence, and robustness to noise and sparsity of the data, on both synthetic and real-world datasets. Furthermore, we extend the models with the Bayesian automatic relevance determination prior, allowing the models to perform automatic model selection, and demonstrate its efficiency

Bridging the data gaps in the epidemiology of hepatitis C virus infection in Malaysia using multi-parameter evidence synthesis

BACKGROUND: Collecting adequate information on key epidemiological indicators is a prerequisite to informing a public health response to reduce the impact of hepatitis C virus (HCV) infection in Malaysia. Our goal was to overcome the acute data shortage typical of low/middle income countries using statistical modelling to estimate the national HCV prevalence and the distribution over transmission pathways as of the end of 2009. METHODS: Multi-parameter evidence synthesis methods were applied to combine all available relevant data sources - both direct and indirect - that inform the epidemiological parameters of interest. RESULTS: An estimated 454,000 (95% credible interval [CrI]: 392,000 to 535,000) HCV antibody-positive individuals were living in Malaysia in 2009; this represents 2.5% (95% CrI: 2.2-3.0%) of the population aged 15-64 years. Among males of Malay ethnicity, for 77% (95% CrI: 69-85%) the route of probable transmission was active or a previous history of injecting drugs. The corresponding proportions were smaller for male Chinese and Indian/other ethnic groups (40% and 71%, respectively). The estimated prevalence in females of all ethnicities was 1% (95% CrI: 0.6 to 1.4%); 92% (95% CrI: 88 to 95%) of infections were attributable to non-drug injecting routes of transmission. CONCLUSIONS: The prevalent number of persons living with HCV infection in Malaysia is estimated to be very high. Low/middle income countries often lack a comprehensive evidence base; however, evidence synthesis methods can assist in filling the data gaps required for the development of effective policy to address the future public health and economic burden due to HCV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0564-6) contains supplementary material, which is available to authorized users

The South Asian genome

Genetics of disease Microarrays Variant genotypes Population genetics Sequence alignment AllelesThe genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.Whole genome sequencing to discover genetic variants underlying type-2 diabetes, coronary heart disease and related phenotypes amongst Indian Asians. Imperial College Healthcare NHS Trust cBRC 2011-13 (JS Kooner [PI], JC Chambers)

Exploring the current and future role of the pharmacists in osteoporosis screening and management in Malaysia

Background Several studies have found that pharmacists can assist in screening and prevention of osteoporosis by referring patients for bone mineral density scans and counselling on lifestyle changes. In Malaysia, screening osteoporosis in all elderly women is not mandatory due to its cost. One approach to address this gap is to develop a pharmacist-led osteoporosis screening and prevention program. However, there is a paucity of data on the perspectives of Malaysian pharmacists in this area. Objective To explore the perspective of stakeholders (policy makers, doctors, pharmacists, nurses and patients) towards the role of pharmacists in osteoporosis screening and management. Setting A primary care clinic located within a teaching hospital in Kuala Lumpur, Malaysia. Method Patients (n = 20), nurses (n = 10), pharmacists (n = 11), doctors (n = 10) and policy makers (n = 5) were individually interviewed using a semi-structured topic guide. Purposive sampling was used. Interviews were transcribed verbatim and analysed using thematic analysis. Main outcome measure Perspective of stakeholders on the current and future role of pharmacists. Results All participants perceived pharmacists to be suppliers of medication, although there was some recognition of roles in providing medication advice. Nonetheless, these stakeholders were eager for pharmacists to expand their non-dispensing roles towards counselling, creating awareness and screening of osteoporosis. Interviewed pharmacists referred to their current role as ‘robotic dispensers’ and unanimously agreed to spread out to osteoporosis management role. Conclusion Under stakeholders there is a willingness to expand the role of pharmacists in Malaysia to non-dispensing roles, particularly in osteoporosis screening and management