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Telomere attrition is an established ageing biomarker and shorter peripheral blood leukocyte telomere length has been associated with increased risks of respiratory diseases. However, whether telomere length in disease-relevant sputum immune cells of chronic respiratory disease patients is shortened and which pathways are dysfunctional are not clear. Here we measured telomere length from sputum samples of bronchiectasis and asthmatic subjects and determined that telomere length in sputum of bronchiectasis subjects was significantly shorter (Beta = - 1.167, P

Palm oil mills generate a large amount of wastewater, known as palm oil mill effluent, during the production of crude palm oil. The high organic contents in palm oil mill effluent have an excellent potential for biogas utilisation. Besides, such effluent must be further treated before discharge or reused in milling processes. In this respect, an integrated biogas and wastewater treatment system should be developed. The aim of this paper is to synthesise and optimise an integrated biogas and wastewater treatment system via a process systems engineering tool that yields maximum economic performance. To illustrate the proposed approach, a typical palm oil mill case study in Malaysia is presented. The variation in palm oil mill effluent availability is considered to evaluate the changes in performance and ensuring the flexibility of the developed system. As shown in the results, implementation of integrated biogas and wastewater treatment system in a typical 60 t/h mill in Malaysia could export up to 1.9 MW electrical power on average. Alternatively, 110,800 GJ/year of compressed biomethane can be produced when feed-in to the national grid is not available. The implementation of integrated biogas and wastewater treatment system successfully reduces greenhouse gas emissions by 50,430 t CO2e/year as compared with the conventional open ponding system practiced in the industry. Lastly, feasibility studies and strategies to promote biogas utilisation in the industry are performed.

Background Information on the extent of high-risk prescribing for nonsteroidal anti-inflammatory drugs (NSAIDs) across developing countries is scarce. Objectives This study examines the prescribing pattern for NSAIDs in primary care, assesses the extent of high-risk NSAIDs prescribing and identifies associated factors. Setting 129 public and 416 private primary care clinics in Malaysia. Methods Data were derived from the National Medical Care Survey 2014, a cross-sectional survey on primary care morbidity patterns and clinical activities in Malaysia. Types of NSAIDs, indications for NSAIDs use and proportion of high-risk NSAIDs prescribing were assessed. Factors associated with high-risk NSAIDs prescribing were identified with a multivariable logistic regression. Weighted results, adjusted for sampling design and non-response were presented. Main outcome measures Prescribing pattern of NSAIDs, proportion of high-risk NSAIDs prescribing and its associated factors. Results Among the 55,489 patients who received NSAIDs, diclofenac was the most frequently prescribed NSAID (40.5%, 95% CI 40.1-40.9%), followed by mefenamic acid (29.2%, 95% CI 28.8-29.6%). The commonest indications for NSAIDs use were musculoskeletal condition and respiratory tract infection, both at 17.8% (95% CI 17.4-18.1%). A total of 22.9% (95% CI 22.6-23.3%) patients received high-risk NSAID prescriptions. Of these, 47.8% (95% CI 46.9-48.7%) did not receive adequate gastroprotection despite being at risk, 24.8% (95% CI 24.0-25.5%) were prescribed NSAIDs despite having cardiovascular comorbidities and 22.4% (95% CI 21.7-23.2%) were prescribed high-dose NSAIDs. The odds of receiving high-risk NSAID prescriptions increased with the number of drugs prescribed (OR 1.23, 95% CI 1.06-1.43) and the number of diagnoses in one visit (OR 2.21, 95% CI 1.71-2.86). The odds of being prescribed high-risk NSAID prescriptions were lower in patients with secondary (OR 0.52, 95% CI 0.35-0.77) and tertiary education (OR 0.39, 95% CI 0.22-0.68) compared to patients without formal education. Patients' citizenship, indication for NSAID prescriptions and whether a medical certificate was issued were also significantly associated with the likelihood of receiving high-risk NSAID prescriptions. Conclusions A quarter of NSAIDs prescribed in Malaysian primary care setting is categorised as high-risk prescribing. Targeted strategies are necessary to improve patient safety.

The prevalence of house dust mites (HDM)-sensitization is high in allergic asthma (AA), especially in tropical/subtropical countries in Asia and South America. As HDM-sensitization can contribute to the subsequent development of HDM-driven asthma, poor asthma control and exacerbations, allergen immunotherapy (AIT) might reduce the growing global burden of allergic asthma. AIT builds immunotolerance via upregulation of T-regulatory (reg) cells, leading to increase secretion of IL-10 and TGF-β which suppress the Th2 response to allergens. IL-10 also induces the class-switch to plasma cells that produce IgG4 that competes with Ig E’s binding on mast cell. Encouragingly, 2 recent multicentre trials showed that HDM AIT could lead to improvements in clinically relevant health outcomes: reduction in asthma exacerbations and inhaled corticosteroid usage. The uptake of AIT remains low due to difficulties with long-term adherence and lack of robust cost-effectiveness studies. There is limited standardization of techniques to compare the efficacy between different AIT administration routes and formulation. In clinical practice, it is challenging to differentiate “asthma with HDM sensitization” from “HDM-driven asthma”. Additionally, Blomia tropicalis (Blo.t) play an important allergenic role especially in tropics, in addition to the Dermatophagoides species but is not found in many AIT formulations. It is uncertain if Blo.t sensitised patients will respond equally to these HDM AIT. We will summarise (a) global differences in HDM sensitization, (b) disease-modifying mechanisms behind HDM AIT (c) differences between the subcutaneous and sublingual route (d) therapeutic strategies in HDM-driven asthma to maximise cost-effectiveness.

Background A major outbreak of the Zika virus (ZIKV) has been reported in Brazil in 2015. Since then, it spread further to other countries in the Americas and resulted in declaration of the Public Health Emergency of International Concern (PHEIC) by World Health Organization. In 2016, Singapore reported its first minor ZIKV epidemic. Malaysia shares similar ecological environment as Brazil and Singapore which may also favor ZIKV transmission. However, no ZIKV outbreak has been reported in Malaysia to date. This study aimed to discuss all confirmed ZIKV cases captured under Malaysia ZIKV surveillance system after declaration of the PHEIC; and explore why Malaysia did not suffer a similar ZIKV outbreak as the other two countries. Methods This was an observational study reviewing all confirmed ZIKV cases detected in Malaysia through the ZIKV clinical surveillance and Flavivirus laboratory surveillance between June 2015 and December 2017. All basic demographic characteristics, co-morbidities, clinical, laboratory and outcome data of the confirmed ZIKV cases were collected from the source documents. Results Only eight out of 4043 cases tested positive for ZIKV infection during that period. The median age of infected patients was 48.6 years and majority was Chinese. Two of the subjects were pregnant. The median interval between the onset of disease and the first detection of ZIKV Ribonucleic Acid (RNA) in body fluid was 3 days. Six cases had ZIKV RNA detected in both serum and urine samples. Phylogenetic analysis suggests that isolates from the 7 cases of ZIKV infection came from two clusters, both of which were local circulating strains. Conclusion Despite similar ecological background characteristics, Malaysia was not as affected by the recent ZIKV outbreak compared to Brazil and Singapore. This could be related to pre-existing immunity against ZIKV in this population, which developed after the first introduction of the ZIKV in Malaysia decades ago. A serosurvey to determine the seroprevalence of ZIKV in Malaysia was carried out in 2017. The differences in circulating ZIKV strains could be another reason as to why Malaysia seemed to be protected from an outbreak.

Background The continuing morbidity and mortality associated with infection with malaria parasites highlights the urgent need for a vaccine. The efficacy of sub-unit vaccines tested in clinical trials in malaria-endemic areas has thus far been disappointing, sparking renewed interest in the whole parasite vaccine approach. We previously showed that a chemically attenuated whole parasite asexual blood-stage vaccine induced CD4+ T cell-dependent protection against challenge with homologous and heterologous parasites in rodent models of malaria. Methods In this current study, we evaluated the immunogenicity and safety of chemically attenuated asexual blood-stage Plasmodium falciparum (Pf) parasites in eight malaria-naïve human volunteers. Study participants received a single dose of 3 × 107 Pf pRBC that had been treated in vitro with the cyclopropylpyrolloindole analogue, tafuramycin-A. Results We demonstrate that Pf asexual blood-stage parasites that are completely attenuated are immunogenic, safe and well tolerated in malaria-naïve volunteers. Following vaccination with a single dose, species and strain transcending Plasmodium-specific T cell responses were induced in recipients. This included induction of Plasmodium-specific lymphoproliferative responses, T cells secreting the parasiticidal cytokines, IFN-γ and TNF, and CD3+CD45RO+ memory T cells. Pf-specific IgG was not detected. Conclusions This is the first clinical study evaluating a whole parasite blood-stage malaria vaccine. Following administration of a single dose of completely attenuated Pf asexual blood-stage parasites, Plasmodium-specific T cell responses were induced while Pf-specific antibodies were not detected. These results support further evaluation of this chemically attenuated vaccine in humans. Trial registration Trial registration: ACTRN12614000228684. Registered 4 March 2014.

Background Burkholderia pseudomallei is a gram negative bacteria that causes a spectrum of human diseases in the tropics. Although melioidosis is endemic in Southeast Asia, large clinical case series were rarely reported from metropolitan Singapore. Methods This is a retrospective study of 219 consecutive patients with culture proven infections due to Burkholderia pseudomallei between the years 2001 to 2016 managed in Singapore General Hospital (SGH). We aimed to review local patients’ characteristics and identify clinical factors associated with mortality and recurrent melioidosis. Results Culture proven melioidosis occurred in 219 patients, 83.1% were male with a mean age of 55.7 ± 14.3 years and 63.0% had diabetes mellitus. Most patients (71.7%) present within 4 weeks of symptom onset and the most common symptom was fever. The majority of patients had bacteremia (67.6%) and had infection involving the respiratory system (71.2%), presenting most frequently with multi-lobar pneumonia. Thirty-four (15.5%) deaths occurred during the initial hospitalisation with a median time from presentation to death of 6.0 days (interquartile range: 2.8–16.3). Twelve patients demised before the diagnosis of melioidosis was made. Univariate analysis identified patients with symptom duration of longer than 4 weeks, bacteremia, and disease requiring mechanical ventilation, inotropic support or temporary dialysis as factors that were significantly associated with mortality. Having bacteremia and disease requiring mechanical ventilation remained statistically significant factors in the multivariable analysis. Twenty-one (11.4%) patients developed at least 1 episode of culture proven recurrent infection, with 15 recurring within the first 12 months of their initial infection. Eight patients developed more than 1 episode of culture proven recurrent infection. Patients with multifocal infection were more likely to develop recurrent infection. Conclusion In metropolitan Singapore, melioidosis was associated with mortality in excess of 15%, where more than a third occurred before diagnosis. This study reminds local physicians that melioidosis is still a serious infection affecting local male diabetic patients and an important differential diagnosis in a patient presenting with severe multi-lobar pneumonia and septic shock. Recurrent infections occurred in 11.4% and the weight-based dosing of oral eradication antibiotics may improve the management of this disease locally.

Background Polypharmacy is particularly important in older persons as they are more likely to experience adverse events compared to the rest of the population. Despite the relevance, there is a lack of studies on the possible association of patient, prescriber and practice characteristics with polypharmacy. Thus, the aim of this study was to determine the rate of polypharmacy among older persons attending public and private primary care clinics, and its association with patient, prescriber and practice characteristics. Methods We used data from The National Medical Care Survey (NMCS), a national cross-sectional survey of patients’ visits to primary care clinics in Malaysia. A weighted total of 22,832 encounters of patients aged ≥65 years were analysed. Polypharmacy was defined as concomitant use of five medications and above. Multilevel logistic regression was performed to examine the association of polypharmacy with patient, prescriber and practice characteristics. Results A total of 20.3% of the older primary care attenders experienced polypharmacy (26.7%% in public and 11.0% in private practice). The adjusted odds ratio (OR) of polypharmacy were 6.37 times greater in public practices. Polypharmacy was associated with patients of female gender (OR 1.49), primary education level (OR 1.61) and multimorbidity (OR 14.21). The variation in rate of polypharmacy was mainly found at prescriber level. Conclusion Polypharmacy is common among older persons visiting primary care practices. Given the possible adverse outcomes, interventions to reduce the burden of polypharmacy are best to be directed at individual prescribers.

Optimization of an integrated anaerobic-aerobic bioreactor (IAAB) treatment system for the reduction of organic matter (Chemical Oxygen Demand (COD), Biochemical Oxygen Demand (BOD) and Total Suspended Solids (TSS) concentrations) in Palm Oil Mill Effluent (POME) to legal standards with high methane yield was performed for the first time under thermophilic condition (50°C–55°C) by using response surface methodology (RSM). The experiments were conducted based on a central composite rotatable design (CCRD) with three independent operating variables, organic loading rates in anaerobic compartment (OLRan) and mixed liquor volatile suspended solids (MLVSS) concentration in anaerobic (MLVSSan) and aerobic compartments (MLVSSa). The optimum conditions for the POME treatment were determined as OLRan of 15.6 g COD·L−1·d−1, MLVSSan of 43100 mg·L−1, and MLVSSa of 18600 mg·L−1, where high aerobic COD, BOD and TSS removal efficiencies of 96.3%, 97.9%, and 98.5% were achieved with treated BOD of 56 mg·L−1 and TSS of 28 mg·L−1 meeting the discharge standard. This optimization study successfully achieved a reduction of 42% in the BOD concentrations of the final treated effluent at a 48% higher OLRan as compared to the previous works. Besides, thermophilic IAAB system scores better feasibility and higher effectiveness as compared to the optimized mesophilic system. This is due to its higher ability to handle high OLR with higher overall treatment efficiencies (more than 99.6%), methane yield (0.31 L CH4·g−1 CODremoved) and purity of methane (67.5%). Hence, these advantages ascertain the applicability of thermophilic IAAB in the POME treatment or even in other high-strength wastewaters treatment.

Transesterification of oils/triglycerides (TGs) with alcohol in the presence of catalyst has been the most commonly used process to produce biodiesel. Major limiting factors of conventional biodiesel transesterification process are phase separation and product purification. Precise and correct knowledge of the phase equilibrium behaviour is crucial for future industrial biodiesel reaction, separation and purification processes. For this purpose, it is important to consider the phase equilibrium behaviour in order to thoroughly understand the entire transesterification system for biodiesel production, which consists of six components. This work is to discuss on the liquid–liquid equilibrium (LLE) data of six-component system which involves TG, palm biodiesel (FAME), methanol (MeOH), glycerine (GLY), diglyceride (DG) and monoglyceride (MG). The phase equilibrium data of this system were determined experimentally through transesterification of crude palm oil (CPO). The experimental LLE data have been transposed into a pseudo-ternary diagram as TG–DG–MG + MeOH–GLY + FAME for better visualisation and understanding of the six-component system. Results showed that the transesterification of TG to FAME has formed a two-phase system where CPO-rich phase and MeOH-rich phase co-existed during the reaction. Due to immiscibility of CPO and MeOH, as well as the miscibility of FAME and MeOH, the LLE data suggested that at specific reaction operating condition, the reacted product (FAME) could be continuously removed by separating the MeOH phase from the CPO phase. This favours the forward transesterification reaction and eventually enhances the reaction efficiency to produce an oil-free FAME.

The mesoporous NH2-MCM-41 adsorbent prepared by grafting aminopropyls on MCM-41 is selective towards gold and palladium adsorptions and can separate these precious metals from complex solutions containing other metal ions such as cobalt, nickel, copper and zinc. Adsorption is rapid and the adsorbent’s capacity for gold is better or comparable to most carbonaceous adsorbents including activated carbons. Furthermore, NH2-MCM-41 can separate palladium from gold solution at pH1.0 with excellent selectivity and capacity. Thus, it is possible to design a two steps separation process for the separation of palladium and then gold from the complex solution. A simple acid wash was sufficient to recover the adsorbed palladium and gold as concentrated, high purity (i.e., > 95%) metal salt solutions and the regenerated adsorbent was reused without lost of performance.

Background Maternal consumption of alcohol during pregnancy is associated with a range of physical, cognitive and behavioural outcomes in the offspring which are collectively called foetal alcohol spectrum disorders. We and others have proposed that epigenetic modifications, such as DNA methylation and post-translational histone modifications, mediate the effects of prenatal alcohol exposure on gene expression and, ultimately, phenotype. Here we use an inbred C57BL/6J mouse model of early gestational ethanol exposure equivalent, developmentally, to the first 3–4 weeks of pregnancy in humans to examine the long-term effects on gene expression and epigenetic state in the hippocampus. Results Gene expression analysis in the hippocampus revealed sex- and age-specific up-regulation of solute carrier family 17 member 6 (Slc17a6), which encodes vesicular glutamate transporter 2 (VGLUT2). Transcriptional up-regulation correlated with decreased DNA methylation and enrichment of histone H3 lysine 4 trimethylation, an active chromatin mark, at the Slc17a6 promoter. In contrast to Slc17a6 mRNA levels, hippocampal VGLUT2 protein levels were significantly decreased in adult ethanol-exposed offspring, suggesting an additional level of post-transcriptional control. MicroRNA expression profiling in the hippocampus identified four ethanol-sensitive microRNAs, of which miR-467b-5p was predicted to target Slc17a6. In vitro reporter assays showed that miR-467b-5p specifically interacted with the 3′UTR of Slc17a6, suggesting that it contributes to the reduction of hippocampal VGLUT2 in vivo. A significant correlation between microRNA expression in the hippocampus and serum of ethanol-exposed offspring was also observed. Conclusions Prenatal ethanol exposure has complex transcriptional and post-transcriptional effects on Slc17a6 (VGLUT2) expression in the mouse hippocampus. These effects are observed following a relatively moderate exposure that is restricted to early pregnancy, modelling human consumption of alcohol before pregnancy is confirmed, and are only apparent in male offspring in adulthood. Our findings are consistent with the idea that altered epigenetic and/or microRNA-mediated regulation of glutamate neurotransmission in the hippocampus contributes to the cognitive and behavioural phenotypes observed in foetal alcohol spectrum disorders. Although further work is needed in both mice and humans, the results also suggest that circulating microRNAs could be used as biomarkers of early gestational ethanol exposure and hippocampal dysfunction. Electronic supplementary material The online version of this article (doi:10.1186/s13072-015-0032-6) contains supplementary material, which is available to authorized users.

Group A streptococcus (GAS) is responsible for causing many clinical complications including the relatively benign streptococcal pharyngitis and impetigo. However, if left untreated, these conditions may lead to more severe diseases such as rheumatic fever (RF) and rheumatic heart disease (RHD). These diseases exhibit high morbidity and mortality, particularly in developing countries and in indigenous populations of affluent countries. As RF and RHD only ever occur following GAS infection, a vaccine offers promise for their prevention. As such, we have investigated the use of the lipid-core peptide (LCP) system for the development of multi-valent prophylactic GAS vaccines. The current study has investigated the capacity of this system to adjuvant up to four different GAS peptide epitopes. Presented are the synthesis and immunological assessment of tetra-valent and tri-valent GAS LCP systems. We demonstrated their capacity to elicit systemic IgG antibody responses in B10.BR mice to all GAS peptide epitopes. The data also showed that the LCP systems were self-adjuvanting. These findings are particularly encouraging for the development of multi-valent LCP-based GAS vaccines.

Petunia x hybridaHort.Vilm.-Andr. was transformed with boers, a mutatedallele of BOERS, an ethylene receptor sensor gene ofBrassica oleracea.boers was obtained by removing anEcoRI cutting site with a silent mutation at Gly-521 andintroducing a point mutation at Ile-62, replacing isoleucine withphenylalanine. Transformation was Agrobacterium tumefaciens mediated.Hygromycin resistant regenerants were tentatively confirmed as transformants byPCR's for HPH and boers and moredefinitively by Southern hybridization of genomic DNA with pBOERS4421. Flowersof transgenic plants retained turgidity and pigmentation considerably longerthan those of untransformed controls, whether left undisturbed on plants orexcised and placed in water. Furthermore, flowers were unaffected by exposureto exogenous ethylene. Excised shoots of transgenic plants released considerablymore ethylene than those of untransformed plants. Transformed plants alsoproduced apparently larger flowers. Unexpectedly higher mortality was observed,suggesting that the ethylene insensitive petunia plants were also lower indisease resistance.