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Babesia spp. are tick-transmitted intra-erythrocytic protozoan parasites that infect humans and animals, causing a flu-like illness and hemolytic anemia. There is currently no human vaccine available. People most at risk of severe disease are the elderly, immunosuppressed, and asplenic individuals. B. microti and B. divergens are the predominant species affecting humans. Here, we present a whole-parasite Babesia vaccine. To establish proof-of-principle, we employed chemically attenuated B. microti parasitized red blood cells from infected mice. To aid clinical translation, we produced liposomes containing killed parasite material. Vaccination significantly reduces peak parasitemia following challenge. B cells and anti-parasite antibodies do not significantly contribute to vaccine efficacy. Protection is abrogated by the removal of CD4+ T cells or macrophages prior to challenge. Importantly, splenectomized mice are protected by vaccination. To further facilitate translation, we prepared a culture-based liposomal vaccine and demonstrate that this performs as a universal vaccine inducing immunity against different human Babesia species.

Reciprocal epithelial-mesenchymal signaling is essential for morphogenesis, including branching of the lung. In the mouse, mesenchymal cells differentiate into airway smooth muscle that wraps around epithelial branches, but this contractile tissue is absent from the early avian lung. Here, we found that branching morphogenesis in the embryonic chicken lung requires extracellular matrix (ECM) remodeling driven by reciprocal interactions between the epithelium and mesenchyme. Before branching, the basement membrane wraps the airway epithelium as a spatially uniform sheath. After branch initiation, however, the basement membrane thins at branch tips; this remodeling requires mesenchymal expression of matrix metalloproteinase-2, which is necessary for branch extension but not branch initiation. As branches extend, tenascin-C (TNC) accumulates in the mesenchyme several cell diameters away from the epithelium. Despite its pattern of accumulation, TNC is expressed exclusively by epithelial cells. Branch extension coincides with deformation of adjacent mesenchymal cells, which correlates with an increase in mesenchymal fluidity at branch tips that may transport TNC away from the epithelium. These data reveal novel epithelial-mesenchymal interactions that direct ECM remodeling during airway branching morphogenesis.

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. Full Text Link:https://dx.doi.org/10.1007/s11096-020-00966-w

The development of a blood-stage malaria vaccine has largely focused on the subunit approach. However, the limited success of this strategy, mainly due to antigenic polymorphism and the failure to maintain potent parasite-specific immune responses, indicates that other approaches must be considered. Whole parasite (WP) vaccines offer many advantages over sub-units; they represent every antigen on the organism, thus limiting the effects of antigenic polymorphism, and similarly they compensate for individual Immune-Response (Ir) gene-regulated non-responsiveness to any particular antigen. From a development perspective, they negate the need to identify and compare the relative efficacies of individual candidate antigens. WP vaccines induce protective immunity that is largely cell-mediated. However, WP blood-stage vaccines present a number of challenges for the development pathway. Key issues are cryopreservation and storage and the possible induction of antibodies against red blood cell surface antigens, even if the parasites are grown in blood group O, Rh negative blood. Here, we used a novel adaptation of an immunomagnetic method from STEMCELL™ Technologies to remove the red cell membranes from human red blood cells parasitized with P. falciparum. We then used these antigens to construct liposomes which were modified to present mannose on their membrane to target the liposome to antigen presenting cells. We then compared the immunogenicity of freshly prepared and lyophilized liposome vaccines. Following vaccination of mice, liposomes induced significantly lower antibody responses to human red cells but potent strain- and species-transcending cell-mediated immune responses to parasite antigens. These data support transitioning the P. falciparum liposomal vaccine into clinical studies.

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.

Synthesis of multifunctional fabrics with long-lasting durability remains a quest for researchers in the past decade. In this work, robust coatings on cotton fabrics for superhydrophobic, antibacterial, and UV-blocking functionalities by a dual-stage silanization technique are reported. Aminopropyltriethoxysilane is utilized as a silane cross-linker to anchor zinc oxide nanoparticles to the pristine cotton fabric surface, followed by modification with a silane hydrophobe, hexadecyltrimethoxysilane. This dual-silanization approach results in highly functional fabrics displaying superhydrophobicity with a water contact angle of 154°, water shedding angle of 2°, antibacterial activity of up to 98%, and UV-blocking ability more than 200 times of pristine cotton. The as-prepared fabrics display excellent durability against abrasion, ultrasonic washing, immersion in different pH solutions, and UV irradiation. Moreover, the air permeability and flexural rigidity of the fabrics are still within the required breathability and wearer comfortability for clothing applications. The reported process is simple, cost-effective, and green, showing great promise for large-scale production of multifunctional fabrics. Accepted version

Naturally acquired immunity to malaria is robust and protective against all strains of the same species of Plasmodium. This develops as a result of repeated natural infection, taking several years to develop., Naturally acquired immunity to malaria is robust and protective against all strains of the same species of Plasmodium. This develops as a result of repeated natural infection, taking several years to develop. Evidence suggests that apoptosis of immune lymphocytes due to uncontrolled parasite growth contributes to the slow acquisition of immunity. To hasten and augment the development of natural immunity, we studied controlled infection immunization (CII) using low-dose exposure to different parasite species (Plasmodium chabaudi, P. yoelii, or P. falciparum) in two rodent systems (BALB/c and C57BL/6 mice) and in human volunteers, with drug therapy commencing at the time of initiation of infection. CIIs with infected erythrocytes and in conjunction with doxycycline or azithromycin, which are delayed death drugs targeting the parasite’s apicoplast, allowed extended exposure to parasites at low levels. In turn, this induced strong protection against homologous challenge in all immunized mice. We show that P. chabaudi/P. yoelii infection initiated at the commencement of doxycycline therapy leads to cellular or antibody-mediated protective immune responses in mice, with a broad Th1 cytokine response providing the best correlate of protection against homologous and heterologous species of Plasmodium. P. falciparum CII with doxycycline was additionally tested in a pilot clinical study (n = 4) and was found to be well tolerated and immunogenic, with immunological studies primarily detecting increased cell-associated immune responses. Furthermore, we report that a single dose of the longer-acting drug, azithromycin, given to mice (n = 5) as a single subcutaneous treatment at the initiation of infection controlled P. yoelii infection and protected all mice against subsequent challenge.

Poor prognosis of most cancer patients is in part, due to limited therapeutic options. Furthermore, as chemotherapy remains the standard-of-care for several cancers, partial or lack of response remains a concern and compounding this are the adverse side effects of the treatment that severely impacts the quality of life and survival. In pursuit of improving treatment options, we have opted to investigate the unique chemical skeleton of natural compounds as anticancer therapies. In this study, from an initial screen of 31 crude methanol extracts from -15 plant species using HL60 cells, the root extract of Bruceajavanica (L.) Merr indicated the presence of bioactive compounds. Subsequent bioassay-guided purification on the root extract yielded two alkaloids canthin-6-one (1) and bruceolline J (2), which were further investigated for their bioactivity in representative human cancer lines and normal phenotypic counterparts. MTT assay demonstrated ED50 values from 34.7-72.9 gM for 1 and 16.0-54.0 gM for 2 for the cancer cell lines panel. NP69 cells also demonstrated sensitivity to. both compounds (9.3 piM and 4.5 pM). As amount of 2 isolated were limiting, we focused on 1 to further identify novel anticancer properties in PC3 and HeLa cancer lines. We observed at 30 gM, I induced a G2/M phase arrest coinciding with decreased cell proliferation. Furthermore, I was able to synergize the cytotoxic effect of cisplatin when used in combination, suggesting the potential of combination therapy for those less responsive lesions to standard chemotherapy.

Cells communicate constantly with their surrounding extracellular matrix (ECM) to maintain homeostasis, using both mechanical and chemical signals. In cancer, abnormal signaling leads to stiffening of the ECM. A stiff microenvironment affects many aspects of the cell, including internal molecular signaling as well as behaviors such as motility and proliferation. Thus, cells and ECM interact in a feedback loop to drive matrix deposition and cross-linking, which alter the mechanical properties of the tissue. Stiffer tissue enhances the invasive potential of a tumor and decreases therapeutic efficacy. This chapter describes how specific molecular effects caused by an abnormally stiff tissue drive macroscopic changes that help determine disease outcome. A complete understanding may foster the generation of new cancer therapies.

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.

Three main parameters of palm oil mill effluent (POME) i.e. biological oxygen demand (BOD), total suspended solids (TSS) and oil and grease (O&G), at high concentrations, have hindered efficient anaerobic digestion (AD) due to sludge flotation and scum formation. In this study, Moringa Oleifera extract was co-digested with POME to allow TSS and O&G to be coagulated and settled, and hence, an immobilisation media formed for better digestibility. Mono-digestion (POME, T1 and M. oleifera extract, T2, separately) served as control while co-digestion involved dosing 50 mL of M. oleifera extract (500 mg/L) into a fixed volume of POME (450 mL) at two feeding modes: daily, day 1 to day 30 (T3) and one-time, day 1 (T4). Treatments T1-T4 were conducted in an enclosed AD system for 30 days and the undesirable organic materials removal efficiencies i.e. BODremoval, TSSremoval and O&Gremoval were compared. POME co-digestion, T4, showed an improved 92% TSSremoval, 94% BODremoval and methane yield of 24.3 mL CH4/g COD removed. The results suggested that the nitrogen-fixing capabilities of anoxic microbial cells enhanced proliferation and growth encapsulated within the immobilisation media. Methanogen bacterial DNAs isolated from POME, granular sludge and anaerobically-treated POME were identified as Methanoculleus spp., Methanolinea spp. and Methanoculleus spp., respectively. Two-step complementary DNA (cDNA) and quantitative polymerase chain reaction (qPCR) confirmed the highest methanogen DNA concentration in T4. Therefore, the naturally occurring underutilised M. oleifera can be an organic coagulant for efficient POME co-digestion with an overall 69% and 59.5% higher methane yield and TSSremoval than mono-digestion.

Bilateral optic disc swelling with bilateral abducens nerve palsy as the first presenting signs of sporadic primary Burkitt's lymphoma (BL) is very rare. We report this in a young immunocompetent individual. Initial misdiagnosis of idiopathic intracranial hypertension was made due to normal brain imaging with elevated opening pressure on lumbar puncture. After 2 months, he developed neurological deficits and neck swellings. Biopsy of swelling revealed BL. He received chemotherapy but succumbed before the second cycle. Signs of raised intracranial pressure warrant meticulous investigation. Multiple high-volume taps of lumbar puncture are advised if clinical suspicion of neurolymphomatosis is high.

The aim of this study was to investigate factors influencing nursing students' intention to use a simulated web-application 'Integrated Nursing Education System' for practicing electronic health documentation. The cross-sectional study was conducted at a Malaysian University that provides undergraduate nursing degree program. A total of 133 undergraduate nursing students in their year 2 to year 4 of the program were recruited. They had accessed the simulated web-application as part of the teaching-learning activities during the academic year 2016/2017. Technology Acceptance Model was used to guide the study. Validated questionnaires were used to measure the students' perceived ease of use, perceived usefulness, attitudes and intention to use the application. Data collection was done at the end of the semester. Data analysis was done using SPSS (19.0) and AMOS (23.0). Perceived usefulness was the most influential factor of the students' intention to use the simulated web-application. Perceived ease of use influenced their perceived usefulness significantly. Nurse educators should explain the usefulness of the simulated web-application before assigning students to access it to practice electronic health documentation. The availability of a stable internet access and IT support is important to influence students' perceived ease of use and intention to use the application.

Breast tumors are stiffer and more hypoxic than nonmalignant breast tissue. Here we report that stiff and hypoxic microenvironments promote the development of breast cancer stem-like cells (CSC) through modulation of the integrin-linked kinase ILK. Depleting ILK blocked stiffness and hypoxia-dependent acquisition of CSC marker expression and behavior, whereas ectopic expression of ILK stimulated CSC development under softer or normoxic conditions. Stiff microenvironments also promoted tumor formation and metastasis in ovo, where depleting ILK significantly abrogated the tumorigenic and metastatic potential of invasive breast cancer cells. We further found that the ILK-mediated phenotypes induced by stiff and hypoxic microenvironments are regulated by PI3K/Akt. Analysis of human breast cancer specimens revealed an association between substratum stiffness, ILK, and CSC markers, insofar as ILK and CD44 were expressed in cancer cells located in tumor regions predicted to be stiff. Our results define ILK as a key mechanotransducer in modulating breast CSC development in response to tissue mechanics and oxygen tension. Cancer Res; 76(18); 5277–87. ©2016 AACR.

Carbene-catalyzed reaction of carboxylic esters has the potential to offer effective synthetic solutions that cannot be readily achieved by using the more conventional aldehyde-type substrates. Here we report the first carbene-catalyzed dynamic kinetic resolution of α,α-disubstituted carboxylic esters with up to 99:1 er and 99% yield. The present study clearly illustrates the unique power of carbene-catalyzed reactions of readily available and easy to handle carboxylic esters. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) Accepted version

Central serous chorioretinopathy (CSCR) is a retinal condition characterized by fluid accumulation in the subretinal space, resulting in neurosensory detachment or pigment epithelial detachment. The risk factors associated with this condition include male gender, middle age, smoking, stress and use of corticosteroids. We report a case of CSCR in a 37-year-old policeman with hypertension and bronchial asthma. He presented with sudden onset of bilateral blurring of central vision for 1 day, worse over the left eye. There were no other significant eye complaints. He is an active smoker and has been on long-term corticosteroids for asthma. On examination, the visual acuity was 6/9 bilaterally. The anterior segment of both eyes was normal. Examination of the right fundus revealed a dome-shaped swelling inferior to the fovea, while the left fundus showed circular detachment of the neurosensory retina at the macula. He was diagnosed to have bilateral central serous chorioretinopathy. He was also counseled to stop smoking. The corticosteroids were continued due to the risk of precipitating an asthma attack if they were withheld. Upon his next review two months later, his condition remained stable. CSCR is usually a self-limited condition, with good visual outcome. A thorough medical, social and drug history should be obtained, and patients advised to modify their lifestyle to eliminate or reduce risk factors such as smoking, stress and corticosteroid use.

We report a case series of dengue maculopathy with different ocular manifestations, managements, visual outcomes and sequelae of patients. All three cases were diagnosed to have dengue fever. Patients presented with symptoms of central scotoma (case 1 and case 3) and blurring of vision (case 2) on Day 9 of dengue fever. Fundus examination showed intra retinal haemorrhages (case 1 and case 2) and macula thickening (case 3). Optical coherence tomography (OCT) revealed macular thickening with intra retinal fluid (case 1) and diffuse retinal thickening (case 3), while in case 2, it had irregular ellipsoid line in OCT. Fundus fluorescence angiography (FFA) revealed parafoveal vasculitis. After treatment with systemic steroids, one patient had good visual outcome (case 2), while two others had a persistent central scotoma due to macula atrophy (case 3). Although it is a self limiting disease, but the mode of treatment is variable. Treatment with corticosteroids may hasten recovery of vision and prevent permanent visual impairment.

An amendment to this paper has been published and can be accessed via the original article.

Palm oil mill effluent has been extensively researched via three different technologies, namely chemical, physicochemical and biological treatment methods. Biological treatment by anaerobic and aerobic means is currently the most commonly used method for palm oil mill effluent. However, the greatest challenge posed by them is the inconsistent biological oxygen demand of 20 mg/L for the final treated effluent. Large amount of investment for additional polishing plant prior to the final discharge has been utilised intentionally to further reduce the biochemical oxygen demand values, but the problem remains unresolved. The performance of current palm oil mill effluent treatment system deployed by the industry was evaluated by comparing two different types of anaerobic treatments: open ponding and covered lagoon systems (with hydraulic and gas mixing). The covered lagoon with hydraulic mixing achieved the highest chemical oxygen demand, total suspended solids, total volatile solids and lignin removal efficiencies of >80% compared to other systems which showed

Oil and grease, carbohydrate, protein, and lignin are the main constituents of high strength wastewaters such as dairy wastewater, cheese whey wastewater, distillery wastewater, pulp and paper mill wastewater, and slaughterhouse wastewaters. These constituents have contributed to various operational problems faced by the high-rate anaerobic bioreactor (HRAB). During the hydrolysis stage of anaerobic digestion (AD), these constituents can be hydrolyzed. Since hydrolysis is known to be the rate-limiting step of AD, the overall AD can be enhanced by improving the hydrolysis stage. This can be done by introducing pretreatment that targets the degradation of these constituents. This review mainly focuses on the biological pretreatment on various high-strength wastewaters by using different types of enzymes namely lipase, amylase, protease, and ligninolytic enzymes which are responsible for catalyzing the degradation of oil and grease, carbohydrate, protein, and lignin respectively. This review provides a summary of enzymatic systems involved in enhancing the hydrolysis stage and consequently improve biogas production. The results show that the use of enzymes improves the biogas production in the range of 7 to 76%. Though these improvements are highly dependent on the operating conditions of pretreatment and the types of substrates. Therefore, the critical parameters that would affect the effectiveness of pretreatment are also discussed. This review paper will serve as a useful piece of information to those industries that face difficulties in treating their high-strength wastewaters for the appropriate process, equipment selection, and design of an anaerobic enzymatic system. However, more intensive studies on the optimum operating conditions of pretreatment in a larger-scale and synergistic effects between enzymes are necessary to make the enzymatic pretreatment economically feasible.

With the growing volume of palm oil production, palm oil mill effluent (POME) is an inevitable by-product that causes serious environmental hazards if discharged directly to the environment. This is mainly due to its high concentrations of chemical oxygen demand (COD) and biochemical oxygen demand (BOD). Note however that, with its high organic content, POME is a great source for biogas production. Therefore, POME pollution abatement coupled with biogas capture and utilisation are vital in order to promote sustainable development goal for the palm oil industry. Conventionally, POME is treated by employing open ponding system without capturing biogas released from the anaerobic process. This treatment system is inefficient, requires large footprint, long hydraulic retention time (HRT) and is unable to consistently comply with the proposed stringent BOD regulatory limit of 20 mg/L to be imposed by Department of Environment (DOE). Hence, the current POME treatment trend is gearing towards biogas capture technology and integrated POME treatment system with the ultimate aim of achieving zero discharge concept in the palm oil mill. This can be achieved by integrating several bioprocesses, with the aim to transform POME into value-added products. This chapter will discuss the current POME treatment and biogas capture technologies, as well as to identify issues and challenges faced by the palm oil miller which deters the development of biogas plants in the mill. Development of biogas from POME will no doubt contribute substantially in Malaysia’s renewable energy sector in the near future.

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.

Introduction Understanding the potential determinants of community healthcare seeking behaviour helps in improving healthcare utilisation and health outcomes within different populations. This in turn will aid the development of healthcare policies and planning for prevention, early diagnosis and management of health conditions. Objective To evaluate patients’ perception of community healthcare seeking behaviour towards both acute and preventive physical and psychosocial health concerns by sex, age and type of primary care setting (as a proxy for affordability of healthcare). Methods A total of 3979 patients from 221 public and 239 private clinics in Malaysia were interviewed between June 2015 and February 2016 using a patient experience survey questionnaire from the Quality and Cost of Primary Care cross-sectional study. Multivariable logistic regression analysis adjusted for the complex survey design was used. Results After adjusting for covariates, more women than men perceived that most people would see their general practitioners for commonly consulted acute and preventive physical and some psychosocial health concerns such as stomach pain (adjusted odds ratio (AOR), 1.64; 95% confidence interval (CI), 1.22–2.21), sprained ankle (AOR, 1.29; 95% CI, 1.06–1.56), anxiety (AOR, 1.32; 95% CI, 1.12–1.55), domestic violence (AOR, 1.35; 95% CI, 1.13–1.62) and relationship problems (AOR, 1.24; 95% CI, 1.02–1.51). There were no significant differences in perceived healthcare seeking behaviour by age groups except for the removal of a wart (AOR, 1.41; 95% CI, 1.12–1.76). Patients who visited the public clinics had generally higher perception of community healthcare seeking behaviour for both acute and preventive physical and psychosocial health concerns compared to those who went to private clinics. Conclusions Our findings showed that sex and healthcare affordability differences were present in perceived community healthcare seeking behaviour towards primary care services. Also perceived healthcare seeking behaviour were consistently lower for psychosocial health concerns compared to physical health concerns.

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.

Cells communicate constantly with their surrounding extracellular matrix (ECM) to maintain homeostasis, using both mechanical and chemical signals. In cancer, abnormal signaling leads to stiffening of the ECM. A stiff microenvironment affects many aspects of the cell, including internal molecular signaling as well as behaviors such as motility and proliferation. Thus, cells and ECM interact in a feedback loop to drive matrix deposition and cross-linking, which alter the mechanical properties of the tissue. Stiffer tissue enhances the invasive potential of a tumor and decreases therapeutic efficacy. This chapter describes how specific molecular effects caused by an abnormally stiff tissue drive macroscopic changes that help determine disease outcome. A complete understanding may foster the generation of new cancer therapies.

Table S1. Demographics of study participants. Table S2. Adverse events reported in study participants in group A. Table S3. Abnormal laboratory values reported in study participants in group A. Figure S1. In vitro growth of P. falciparum 7G8 following treatment with different doses of tafuramycin-A. Figure S2. Induction of P. falciparum 7G8 IgG responses in study participants inoculated with a single dose of (A) 3 × 107P. falciparum 7G8 pRBC treated with 50 nM of TF-A or (B) 3 × 107P. falciparum 7G8 pRBC treated with 200 nM of TF-A. Figure S3. Cytokine responses to P. falciparum 7G8 in study participants inoculated with a single dose of (A) 3 × 107P. falciparum 7G8 pRBC treated with 50 nM (group A) or (B) 200 nM (group B) TF-A. Figure S4. Serum cytokine responses in study participants inoculated with a single dose of (A) 3 × 107P. falciparum 7G8 pRBC treated with 50 nM TF-A (group A) or (B) 1,800 P. falciparum 7G8 pRBC (infectivity study) untreated. Figure S5. Monofunctional and polyfunctional CD3+ T cells in study participants inoculated with a single dose of 3 × 107P. falciparum 7G8 pRBC treated with 50 nM TF-A (group A). Figure S6. Cytokine production in naïve and memory T lymphocytes in study participants inoculated with a single dose of 3 × 107P. falciparum 7G8 pRBC treated with 50 nM TF-A (group A). Figure S7. Cytokine production in CD3+ lymphocyte sub-populations in study participants inoculated with a single dose of 3 × 107P. falciparum 7G8 pRBC treated with 50 nM TF-A (group A). (PDF 675 kb)

Yoga has recently been touted as a means to improve physical and mental well-being. However, no form of exercise is without its risks. A 32-year-old Chinese female with moderate myopia complained of right eye sudden onset of floaters and mild blurring of vision after the head-down posture. The visual acuity was 6/12 in the right eye and 6/9 in the left eye. A right eye fundus examination showed posterior vitreous detachment, with a small blood clot located at the inferior margin of the optic disc. The patient was diagnosed with right eye vitreous hemorrhage secondary to acute posterior vitreous detachment and was managed conservatively. Acute changes in posture, especially between an upright and a head-down position, may cause acute posterior vitreous detachment. As yoga practitioners may be required to assume this head-down position, myopic patients should be warned of the possible ocular complications of this exercise.