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Aims Design Methods Results Conclusion Implications for the profession and/or patient care Patient or Public Contribution To evaluate factors associated with fall protection motivation to engage in fall preventive behaviour among rural community‐dwelling older adults aged 55 and above using the protection motivation theory scale.A cross‐sectional study.The study was conducted in a healthcare clinic in Malaysia, using multistage random sampling from November 2021 to January 2022. Three hundred seventy‐five older adults aged 55 and older were included in the final analysis. There were 31 items in the final PMT scale. The analysis was performed within the whole population and grouped into ‘faller’ and ‘non‐faller’, employing IBM SPSS version 26.0 for descriptive, independent t‐test, chi‐square, bivariate correlation and linear regressions.A total of 375 older participants were included in the study. Fallers (n = 82) and non‐fallers (n = 293) show statistically significant differences in the characteristics of ethnicity, assistive device users, self‐rating of intention and participation in previous fall prevention programmes. The multiple linear regression model revealed fear, coping appraisal and an interaction effect of fear with coping appraisal predicting fall protection motivation among older adults in rural communities.Findings from this study demonstrated that coping appraisal and fear predict the protection motivation of older adults in rural communities. Older adults without a history of falls and attaining higher education had better responses in coping appraisal, contributing to a reduction in perceived rewards and improving protection motivation. Conversely, older adults from lower education backgrounds tend to have higher non‐preventive behaviours, leading to a decline in fall protection motivation.These results contribute important information to nurses working with older adults with inadequate health literacy in rural communities, especially when planning and designing fall prevention interventions. The findings would benefit all nurses, healthcare providers, researchers and academicians who provide care for older adults.Participants were briefed about the study, and their consent was obtained. They were only required to answer the questionnaire through interviews. Older individuals aged fifty‐five and above in rural communities at the healthcare clinic who could read, write or understand Malay or English were included. Those who were suffering from mental health problems and refused to participate in the study were excluded from the study. Their personal information remained classified and not recorded in the database during the data entry or analysis. [ABSTRACT FROM AUTHOR]

Tumour-associated angiogenesis play key roles in tumour growth and cancer metastasis. Consequently, several anti-angiogenic drugs such as sunitinib and axitinib have been approved for use as anti-cancer therapies. However, the majority of these drugs target the vascular endothelial growth factor A (VEGFA)/VEGF receptor 2 (VEGFR2) pathway and have shown mixed outcome, largely due to development of resistances and increased tumour aggressiveness. In this study, we used the zebrafish model to screen for novel anti-angiogenic molecules from a library of compounds derived from natural products. From this, we identified canthin-6-one, an indole alkaloid, which inhibited zebrafish intersegmental vessel (ISV) and sub-intestinal vessel development. Further characterisation revealed that treatment of canthin-6-one reduced ISV endothelial cell number and inhibited proliferation of human umbilical vein endothelial cells (HUVECs), suggesting that canthin-6-one inhibits endothelial cell proliferation. Of note, canthin-6-one did not inhibit VEGFA-induced phosphorylation of VEGFR2 in HUVECs and downstream phosphorylation of extracellular signal-regulated kinase (Erk) in leading ISV endothelial cells in zebrafish, suggesting that canthin-6-one inhibits angiogenesis independent of the VEGFA/VEGFR2 pathway. Importantly, we found that canthin-6-one impairs tumour-associated angiogenesis in a zebrafish B16F10 melanoma cell xenograft model and synergises with VEGFR inhibitor sunitinib malate to inhibit developmental angiogenesis. In summary, we showed that canthin-6-one exhibits anti-angiogenic properties in both developmental and pathological contexts in zebrafish, independent of the VEGFA/VEGFR2 pathway and demonstrate that canthin-6-one may hold value for further development as a novel anti-angiogenic drug. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to evaluate an evidence‐based fall risk screening tool to predict the risk of falls suitable for independent community‐dwelling older adults guided by the World Health Organization's International Classification of Functioning, Disability and Health (WHO‐ICF) components, and to examine the reliability and validity of the fall risk screening tool to predict fall risks, and to examine the feasibility of tools among independent community‐dwelling older adults. Methods: A systematic literature search guided by the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement was performed using the EBSCOHost® platform, ScienceDirect, Scopus and Google Scholar between July and August 2021. Studies from January 2010 to January 2021 were eligible for review. Nine articles were eligible and included in this systematic review. The risk of bias assessment used the National Institutes of Health quality assessment tool for observational cohort and cross‐sectional studies. The WHO‐ICF helped to guide the categorization of fall risk factors. Results: Seven screening tools adequately predicted fall risk among community‐dwelling older adults. Six screening tools covered most of the components of the WHO‐ICF, and three screening tools omitted the environmental factors. The modified 18‐item Stay Independent Brochure demonstrated most of the predictive values in predicting fall risk. All tools are brief and easy to use in community or outpatient settings. Conclusion: The review explores the literature evaluating fall risk screening tools for nurses and other healthcare providers to assess fall risk among independent community‐dwelling older adults. A fall risk screening tool consisting of risk factors alone might be able to predict fall risk. However, further refinements and validations of the tools before use are recommended. Summary statement: What is already known about this topic? Many fall risk screening tools are available for nurses and other healthcare providers to assess fall risk among independent community‐dwelling older adults.Some fall risk screening tools underestimate older adults' risk of falling. What this paper adds? Seven of nine fall risk screening tools adequately predict fall risk among independent community‐dwelling older adults.The World Health Organization's International Classification of Functioning, Disability and Health (WHO‐ICF) components (body functions and structures, activities and participation, personal factors and environmental factors) are helpful in guiding the categorization and identification of fall risk factors among independent community‐dwelling older adults.The modified 18‐item Stay Independent Brochure could be a good alternative fall risk screening tool. The implications of this paper: Healthcare professionals are encouraged to read, refine and validate available fall risk screening tools before use to avoid underestimating older adults' risk of falling.Furthermore, continuous staff development activities, training and performance review are necessary to enhance and support nurses and other healthcare providers' practice of fall risk screening. [ABSTRACT FROM AUTHOR]

Aims: In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex. Methods and results: Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n = 16 917; 21.7% females), registry patients eligible for RCT inclusion (n = 26 104; 31.8% females), and registry patients ineligible for RCT inclusion (n = 20 810; 30.2% females). Clinical endpoints included all‐cause mortality, cardiovascular mortality, and first HF hospitalization at 1 year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One‐year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT‐eligible, and RCT‐ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT‐eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62–0.83), while RCT males showed higher adjusted mortality rates compared to RCT‐eligible males (SMR 1.16; 95% CI 1.09–1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76–1.03 for females, SMR 1.43; 95% CI 1.33–1.53 for males). Conclusion: Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries. [ABSTRACT FROM AUTHOR]

Host factors leading to pulmonary nontuberculous mycobacteria (PNTM) disease are poorly understood compared with disseminated NTM disease, which is linked to the interleukin 12–interferon gamma signaling pathway. We investigated the tumor necrosis factor receptor associated factor 3 (TRAF3) R338W variant in a patient with recurrent PNTM infection, demonstrating TRAF3- and TNF-α-deficient phenotypes via ex vivo immune and cloning-transfection cellular studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumour heterogeneity is a phenomenon where the cancer cells evolve diversely over the course of the disease. As a result of the evolution, the cancer cells can be found to be genetically, epigenetically and/or phenotypically different in order to survive in the human body. The tumour microenvironment also plays a crucial role during the evolution. This review compiles the recent developments in melanoma tumour heterogeneity and how heterogeneity impacts the evolution of the disease. The recent findings have greatly improved our knowledge on heterogeneity in melanoma, but there remain many unanswered questions. There is growing evidence that tumour heterogeneity has an imperative role in cancer development, evolution and resistance to therapy. Continuing advancements in biomedical research enable tumour heterogeneity to be observed and studied more critically. As one of the most heterogeneous human cancers, melanoma displays a high level of biological complexity during disease progression. However, much is still unknown regarding melanoma tumour heterogeneity, as well as the role it plays in disease progression and treatment response. This review aims to provide a concise summary of the importance of tumour heterogeneity in melanoma. [ABSTRACT FROM AUTHOR]

Malaria is a vector born parasitic disease causing millions of deaths every year. Despite the high mortality rate, an effective vaccine against this mosquito-borne infectious disease is yet to be developed. Up to date, RTS,S/AS01 is the only vaccine available for malaria prevention; however, its efficacy is low. Among a variety of malaria antigens, merozoite surface protein-1(MSP-1) and ring-infected erythrocyte surface antigen (RESA) have been proposed as promising candidates for malaria vaccine development. We developed peptide-based Plasmodium falciparum vaccine candidates that incorporated three previously reported conserved epitopes from MSP-1 and RESA into highly effective liposomal polyleucine delivery system. Indeed, MSP-1 and RESA-derived epitopes conjugated to polyleucine and formulated into liposomes induced higher epitope specific antibody titres. However, immunized mice failed to demonstrate protection in a rodent malaria challenge study with Plasmodium yoelii. In addition, we found that the three reported P. falciparum epitopes did not to share conformational properties and high sequence similarity with P. yoelii MSP-1 and RESA proteins, despite the epitopes were reported to protect mice against P. yoelii challenge. [ABSTRACT FROM AUTHOR]

Objectives: This review aims to identify types of the existing fall prevention education (FPE) and their effectiveness in promoting fall risk awareness, knowledge and preventive fall behaviour change among community‐dwelling older people. Background: FPE is a cost‐effective and helpful tool for reducing fall occurrences. Evaluation: This is a systematic review study using electronic searches via EBSCOHost® platform, ScienceDirect, Scopus and Google Scholar in March 2021. The review protocol was registered with PROSPERO (CRD42021232102). The Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) statement flow chart guided the search strategy. Articles published from January 2010 to March 2021 were included for quality appraisal using the 'Transparent Reporting of Evaluations with Non‐randomised Designs' (TREND) and the 'Consolidated Standards of Reporting Trials' (CONSORT) statement for randomised controlled trial studies. Key issues: Six FPE studies selected emphasised on personal health status, exercise and environmental risk factors. These studies reported an increase in fall risk awareness or knowledge and a positive change in fall preventive behaviours. Two studies included nurses as educators in FPE. Conclusion: FPE evidently improved awareness or knowledge and preventive fall behaviour change among older adults. Nurses are in great potential in planning and providing FPE for older adults in community settings. Implications for Nursing Management: Expand nurses' roles in fall prevention programmes in community settings by using high‐quality and evidence‐based educational tools. Highlight the nurse's role and collaborative management in FPE. [ABSTRACT FROM AUTHOR]

Introduction: There are few sources of published data on intra-cluster correlation coefficients (ICCs) amongst patients with type 2 diabetes (T2D) and/or hypertension in primary care, particularly in low- and middle-income countries. ICC values are necessary for determining the sample sizes of cluster randomized trials. Hence, we aim to report the ICC values for a range of measures from a cluster-based interventional study conducted in Malaysia.Method: Baseline data from a large study entitled Evaluation of Enhanced Primary Health Care interventions in public health clinics (EnPHC-EVA: Facility) were used in this analysis. Data from 40 public primary care clinics were collected through retrospective chart reviews and a patient exit survey. We calculated the ICCs for processes of care, clinical outcomes and patient experiences in patients with T2D and/or hypertension using the analysis of variance approach.Results: Patient experience had the highest ICC values compared to processes of care and clinical outcomes. The ICC values ranged from 0.01 to 0.48 for processes of care. Generally, the ICC values for processes of care for patients with hypertension only are higher than those for T2D patients, with or without hypertension. However, both groups of patients have similar ICCs for antihypertensive medications use. In addition, similar ICC values were observed for clinical outcomes, ranging from 0.01 to 0.09. For patient experience, the ICCs were between 0.03 (proportion of patients who are willing to recommend the clinic to their friends and family) and 0.25 (for Patient Assessment of Chronic Illness Care item 9, Given a copy of my treatment plan).Conclusion: The reported ICCs and their respective 95% confidence intervals for T2D and hypertension will be useful for estimating sample sizes and improving efficiency of cluster trials conducted in the primary care setting, particularly for low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Background: Variation at different levels of diabetes care has not yet been quantified for low- and middle-income countries. Understanding this variation and its magnitude is important to guide policy makers in designing effective interventions. This study aims to quantify the variation in the control of glycated haemoglobin (HbA1c), systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) for type 2 diabetes (T2D) patients at the clinic and patient level and determine patient and clinic factors associated with control of these outcomes in T2D. Methods: This is a cross-sectional study within the baseline data from the impact evaluation of the Enhanced Primary Health Care (EnPHC) intervention on 40 public clinics in Malaysia. Patients aged 30 and above, diagnosed with T2D, had a clinic visit for T2D between 01 Nov 2016 and 30 April 2017 and had at least one HbA1c, SBP and LDL-C measurement within 1 year from the date of visit were included for analysis. Multilevel linear regression adjusting for patient and clinic characteristics was used to quantify variation at the clinic and patient levels for each outcome. Results: Variation in intermediate clinical outcomes in T2D lies predominantly (93% and above) at the patient level. The strongest predictors for poor disease control in T2D were the proxy measures for disease severity including duration of diabetes, presence of microvascular complications, being on insulin therapy and number of antihypertensives. Among the three outcomes, HbA1c and LDL-C results provide greatest opportunity for improvement. Conclusion: Clinic variation in HbA1c, SBP and LDL-C accounts for a small percentage from total variation. Findings from this study suggest that standardised interventions need to be applied across all clinics, with a focus on customizing therapy based on individual patient characteristics. [ABSTRACT FROM AUTHOR]

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. 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). 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. 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. 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. [ABSTRACT FROM AUTHOR]

Objective: To determine the extent of self-management support (SMS) provided to primary care patients with type 2 diabetes (T2D) and hypertension and its associated factors.Design: Cross-sectional survey conducted between April and May 2017.Setting: Forty public clinics in Malaysia.Participants: A total of 956 adult patients with T2D and/or hypertension were interviewed.Main Outcome Measures: Patient experience on SMS was evaluated using a structured questionnaire of the short version Patient Assessment of Chronic Illness Care instrument, PACIC-M11. Linear regression analysis adjusting for complex survey design was used to determine the association of patient and clinic factors with PACIC-M11 scores.Results: The overall PACIC-M11 mean was 2.3(SD,0.8) out of maximum of 5. The subscales' mean scores were lowest for patient activation (2.1(SD,1.1)) and highest for delivery system design/decision support (2.9(SD,0.9)). Overall PACIC-M11 score was associated with age, educational level and ethnicity. Higher overall PACIC-M11 ratings was observed with increasing difference between actual and expected consultation duration [β = 0.01; 95% CI (0.001, 0.03)]. Better scores were also observed among patients who would recommend the clinic to friends and family [β = 0.19; 95% CI (0.03, 0.36)], when health providers were able to explain things in ways that were easy to understand [β = 0.34; 95% CI (0.10, 0.59)] and knew about patients' living conditions [β = 0.31; 95% CI (0.15, 0.47)].Conclusions: Our findings indicated patients received low levels of SMS. PACIC-M11 ratings were associated with age, ethnicity, educational level, difference between actual and expected consultation length, willingness to recommend the clinic and provider communication skills. [ABSTRACT FROM AUTHOR]

The Wnt/β-catenin pathway controls a variety of cellular behaviors, aberrant activation of which are associated with tumor progression in several types of cancer. The same cellular behaviors are also affected by the mechanical properties of the extracellular matrix (ECM) substratum, which induces signaling through integrins and integrin-linked kinase (ILK). Here, we examined the role of substratum stiffness in the regulation of cell proliferation downstream of Wnt3a. We found that treatment with Wnt3a increased proliferation of cells cultured on stiff substrata, with compliances characteristic of breast tumors, but not of cells on soft substrata, with compliances comparable to that of normal mammary tissue. Depleting ILK rendered cells unresponsive to Wnt3a on both substrata. Ectopic expression of ILK permitted Wnt3a to induce proliferation of cells on both microenvironments, although proliferation on soft substrata remained lower than that on stiff substrata. We further showed that ILK regulates expression of the Wnt receptor frizzled-1 (Fzd1), suggesting the presence of a positive feedback loop between Wnt3a, ILK and Fzd1. These findings suggest that tissue mechanics regulates the cellular response to Wnt under physiological and pathological microenvironmental conditions. [ABSTRACT FROM AUTHOR]

This paper reports a techno-economic assessment for industrial scale bio-flocculant production with okra as biomass feedstock. The sludge dewatering ability of the bio-flocculant was evaluated prior to economic analysis. Several optimisation strategies were investigated in order to lower the bio-flocculant production cost. The results showed that continuous mode microwave extraction was more economically beneficial than conventional extraction in batch and continuous modes. Sensitivity analysis revealed that the production cost was significantly affected by annual production and extract yield, and moderately influenced by raw material price. The optimised scheme for bio-flocculant production was continuous mode microwave extraction at 90° C, a residence time of 10 minutes, a water loading of 3.5 w/w and production rate of 220 tonnes per year. The economic assessment showed that the gross margin was positive, return on investment was in the expected range of 20 to 30% and payback time was within 5 years. [ABSTRACT FROM AUTHOR]

Mechanical forces are increasingly recognized to regulate morphogenesis, but how this is accomplished in the context of the multiple tissue types present within a developing organ remains unclear. Here, we use bioengineered 'microfluidic chest cavities' to precisely control the mechanical environment of the fetal lung. We show that transmural pressure controls airway branching morphogenesis, the frequency of airway smooth muscle contraction, and the rate of developmental maturation of the lungs, as assessed by transcriptional analyses. Time-lapse imaging reveals that branching events are synchronized across distant locations within the lung, and are preceded by long-duration waves of airway smooth muscle contraction. Higher transmural pressure decreases the interval between systemic smooth muscle contractions and increases the rate of morphogenesis of the airway epithelium. These data reveal that the mechanical properties of the microenvironment instruct crosstalk between different tissues to control the development of the embryonic lung. [ABSTRACT FROM AUTHOR]

A growing number of social psychological theories have posited that meaning-striving can be compensated for across domains; threats in one area can simply be addressed by gains in another. Other models argue that not all forms of meaning are created equal; certain forms of striving trump other ones. This review compares the assertions made by these different models related to meaning to illustrate that (a) with few exceptions, fluidity is central to meaning, and (b) despite such consensus on the fluid nature of meaning, existing models diverge on the existence and nature of "ultimate" meanings. Future directions for the empirical study of meaning and methodological considerations are discussed. [ABSTRACT FROM AUTHOR]

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 a,a-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary The airway epithelium develops into a tree-like structure via branching morphogenesis. Here, we show a critical role for localized differentiation of airway smooth muscle during epithelial bifurcation in the embryonic mouse lung. We found that during terminal bifurcation, changes in the geometry of nascent buds coincided with patterned smooth muscle differentiation. Evaluating spatiotemporal dynamics of α-smooth muscle actin (αSMA) in reporter mice revealed that αSMA-expressing cells appear at the basal surface of the future epithelial cleft prior to bifurcation and then increase in density as they wrap around the bifurcating bud. Disrupting this stereotyped pattern of smooth muscle differentiation prevents terminal bifurcation. Our results reveal stereotyped differentiation of airway smooth muscle adjacent to nascent epithelial buds and suggest that localized smooth muscle wrapping at the cleft site is required for terminal bifurcation during airway branching morphogenesis. [ABSTRACT FROM AUTHOR]

The production of natural biopolymers as flocculants for water treatment is highly desirable due to their inherent low toxicity and low environmental footprint. In this study, bio-flocculants were extracted from Hibiscus/Abelmoschus esculentus (okra) by using a water extraction method, and the extract yield and its performance in sludge dewatering were evaluated. Single factor experimental design was employed to obtain the optimum conditions for extraction temperature (25–90 °C), time (0.25–5 h), solvent loading (0.5–5 w/w) and agitation speed (0–225 rpm). Results showed that extraction yield was affected non-linearly by all experimental variables, whilst the sludge dewatering ability was only influenced by the temperature of the extraction process. The optimum extraction conditions were obtained at 70 °C, 2 h, solvent loading of 2.5 w/w and agitation at 200 rpm. Under the optimal conditions, the extract yield was 2.38%, which is comparable to the extraction of other polysaccharides (0.69–3.66%). The bio-flocculants displayed >98% removal of suspended solids and 68% water recovery during sludge dewatering, and were shown to be comparable with commercial polyacrylamide flocculants. This work shows that bio-flocculants could offer a feasible alternative to synthetic flocculants for water treatment and sludge dewatering applications, and can be extracted using only water as a solvent, minimising the environmental footprint of the extraction process. [ABSTRACT FROM AUTHOR]

Natural bio-flocculants were extracted from okra and Chinese yam using water extraction method, and the extract yield and their flocculating abilities were evaluated. Results showed that extraction of okra with seed removal and incubation followed by freeze drying enhanced the extract yield by 91% and improved the flocculating ability greatly by achieving solids removal of above 99% when compared with extraction without incubation and followed by oven drying. The effect of an incubation step was further investigated by using Chinese yam. With incubation, a higher extract yield of 2.95% was obtained compared with the extraction without incubation at 2.13% and high flocculating ability was achieved at 99.5% solids removal. To further investigate the application of bio-flocculants, the samples with the highest extract yield and flocculating ability were selected for a case study focusing on treatment of oleochemical wastewater. Yam bio-flocculant showed its flocculating activity with 80% solids removal when it was coupled with coagulant without pH alteration. However, pH adjustment was required for okra bio-flocculant. In conclusion, highly efficient okra and yam bio-flocculants were successfully extracted and their applicability to wastewater treatment was proven. [ABSTRACT FROM AUTHOR]

Background Rapid diagnostic tests (RDTs) for detection of Plasmodium falciparum infection that target P. falciparum histidine-rich protein 2 (PfHRP2), a protein that circulates in the blood of patients infected with this species of malaria, are widely used to guide case management. Understanding determinants of PfHRP2 availability in circulation is therefore essential to understanding the performance of PfHRP2-detecting RDTs. Methods The possibility that pre-formed host anti-PfHRP2 antibodies may block target antigen detection, thereby causing false negative test results was investigated in this study. Results Anti-PfHRP2 antibodies were detected in 19/75 (25%) of plasma samples collected from patients with acute malaria from Cambodia, Nigeria and the Philippines, as well as in 3/28 (10.7%) asymptomatic Solomon Islands residents. Pre-incubation of plasma samples from subjects with high-titre anti-PfHRP2 antibodies with soluble PfHRP2 blocked the detection of the target antigen on two of the three brands of RDTs tested, leading to false negative results. Pre-incubation of the plasma with intact parasitized erythrocytes resulted in a reduction of band intensity at the highest parasite density, and a reduction of lower detection threshold by ten-fold on all three brands of RDTs tested. Conclusions These observations indicate possible reduced sensitivity for diagnosis of P. falciparum malaria using PfHRP2-detecting RDTs among people with high levels of specific antibodies and low density infection, as well as possible interference with tests configured to detect soluble PfHRP2 in saliva or urine samples. Further investigations are required to assess the impact of pre-formed anti-PfHRP2 antibodies on RDT performance in different transmission settings. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease that can affect any part of the human body including the eyes. Common blinding ocular manifestations include central retinal artery occlusion (CRAO), central retinal vein occlusion (CRVO), severe vaso-occlusive retinopathy, and optic nerve involvement. Antiphospholipid syndrome (APS) in lupus is usually associated with large vessel occlusions and needs prompt treatment with anticoagulant. We are reporting two cases of APS in SLE patients that presented with CRVO (case 1) and vaso-occlusive lupus retinopathy (case 2). Both cases were positive for antiphospholipid antibody (APA) and were treated with immunosuppression, anticoagulant, and laser treatment. Thus, screening for APA is vital in SLE patients with lupus retinopathy, as prompt treatment with anticoagulants is important to prevent further vascular thrombosis, which worsens the visual prognosis. [ABSTRACT FROM AUTHOR]

Studies on menopause-related quality of life (QoL), especially using the Menopausal Rating Scale (MRS), in Asian women are scarce. This study surveyed menopausal symptoms in a convenience sample of 442 Chinese women aged 40–60 years who attended the Well-Women Clinic, Macau, China, in a public health center. The questionnaire included sociodemographic data, the MRS, and a novel question on which area of QoL was affected. The average age of the participants was 49.2 ± 5.08 years, and 98.9% of them reported experiencing menopausal symptoms. The four most prevalent menopausal symptoms were physical and mental exhaustion (90.3%), joint and muscle discomfort (88.5%), irritability (78.1%), and sleep problems (77.1%). The average MRS score was 14.2 ± 8.80. A severe MRS score (≥17) was found in 35.5% of participants. Severe scores in the psychological, somatic, and urogenital MRS subscales were found in 17.9%, 42.8%, and 34.8%, of women, respectively. Menopausal symptoms affected QoL in 57.2% of women: daily life in 36.7%, work in 29.2%, sexual life in 17.0%, and relationship with husband in 13.8%. Daily life was significantly affected by hot flushes and joint/muscular discomfort; work was reportedly affected by irritability and exhaustion; sexual life was reported to be affected by hot flushes, sexual problems, and vaginal dryness, and relationship with husband was affected by sexual problems. We concluded that menopausal symptoms were highly prevalent among midlife Chinese women and often affected their QoL. The MRS, however, did not have a high sensitivity in detecting impaired QoL. [ABSTRACT FROM AUTHOR]

Palm Oil Mill Effluent (POME) treatment has always been a topic of research in Malaysia. This effluent that is extremely rich in organic content needs to be properly treated to minimize environmental hazards before it is released into watercourses. The main aim of this work is to evaluate the potential of applying natural, chemically and thermally modified banana peel as sorbent for the treatment of biologically treated POME. Characteristics of these sorbents were analyzed with BET surface area and SEM. Batch adsorption studies were carried out to remove color, total suspended solids (TSS), chemical oxygen demand (COD), tannin and lignin, and biological oxygen demand (BOD) onto natural banana peel (NBP), methylated banana peel (MBP), and banana peel activated carbon (BPAC) respectively. The variables of pH, adsorbent dosage, and contact time were investigated in this study. Maximum percentage removal of color, TSS, COD, BOD, and tannin and lignin (95.96%, 100%, 100%, 97.41%, and 76.74% respectively) on BPAC were obtained at optimized pH of 2, contact time of 30 h and adsorbent dosage of 30 g/100 ml. The isotherm data were well described by the Redlich–Peterson isotherm model with correlation coefficient of more than 0.99. Kinetic of adsorption was examined by Langergren pseudo first order, pseudo second order, and second order. The pseudo second order was identified to be the governing mechanism with high correlation coefficient of more than 0.99. [Copyright &y& Elsevier]

Abstract: The chemical and phase equilibrium is important to be computed simultaneously in lipid transesterification which occurs in a two-phase system. Such analysis is highly desired to ease the reactor design and optimization problems. The objective of this study is to conduct a thorough investigation on lipid transesterification in a continuous stirred tank reactor (CSTR) with the consideration of chemical phase equilibrium (CPE) via modeling and simulation analysis. The transesterification of canola oil with methanol to fatty acid methyl ester was considered in this study. The UNIQUAC thermodynamic model was used to investigate the liquid–liquid equilibrium (LLE) behavior of the six-component system formed during the biodiesel production. By comparing the LLE behavior between ternary and six-component systems, the data shows that six-component system gave a better representation of the main phase variation in the transesterification process. In addition, the CPE model developed in this study was verified by comparing the simulated results with the results obtained from the transesterification reaction experiments in CSTR. The results obtained from the CPE model analysis show that the proposed CPE model is adequate to be used for the description of simultaneous chemical reaction and phase equilibrium during the transesterifcation process at an acceptable accuracy. The CPE investigation shows that if an efficient reaction needs to be achieved, the CPE needs to be controlled to obtain higher concentration gradients between the two reacting phases. [Copyright &y& Elsevier]

Abstract: Thermophilic treatment of palm oil mill effluent (POME) was studied in a novel integrated anaerobic–aerobic bioreactor (IAAB). The IAAB was subjected to a program of steady-state operation over a range of organic loading rate (OLR)s, up to 30g COD/Lday in order to evaluate its treatment capacity. The thermophilic IAAB achieved high chemical oxygen demand (COD), biochemical oxygen demand (BOD) and total suspended solids (TSS) removal efficiencies of more than 99% for OLR up to 18.5g COD/Lday. High methane yield of 0.32LCH4 (STP)/g CODremoved with compliance of the final treated effluent to the discharge limit were achieved. This is higher than that of the mesophilic system due to the higher maximum specific growth rate (μ max) of the thermophilic microorganisms. Besides, coupling the model of Grau second order model (anaerobic system) with the model of Monod (aerobic system) will completely define the IAAB system. [Copyright &y& Elsevier]

The coxsackie- and adenovirus receptor (CAR) is a cell adhesion molecule predominantly associated with epithelial tight junctions in adult tissues. CAR is also expressed in cardiomyocytes and essential for heart development up to embryonic day 11.5, but not thereafter. CAR is not expressed in vascular endothelial cells but was recently detected in neonatal lymphatic vessels, suggesting that CAR could play a role in the development of the lymphatic system. To address this, we generated mice carrying a conditional deletion of the CAR gene (Cxadr) and knocked out CAR in the mouse embryo at different time points during post-cardiac development. Deletion of Cxadr from E12.5, but not from E13.5, resulted in subcutaneous edema, hemorrhage and embryonic death. Subcutaneous lymphatic vessels were dilated and structurally abnormal with gaps and holes present at lymphatic endothelial cell-cell junctions. Furthermore, lymphatic vessels were filled with erythrocytes showing a defect in the separation between the blood and lymphatic systems. Regionally, erythrocytes leaked out into the interstitium from leaky lymphatic vessels explaining the hemorrhage detected in CAR-deficient mouse embryos. The results show that CAR plays an essential role in development of the lymphatic vasculature in the mouse embryo by promoting appropriate formation of lymphatic endothelial cell-cell junctions. [ABSTRACT FROM AUTHOR]

Abstract: Palm oil mill effluent (POME) with average chemical oxygen demand (COD) and biochemical oxygen demand (BOD) of 70,000 and 30,000mg/L, respectively, can cause serious environmental hazards if discharged untreated. There are conventional palm oil mill effluent (POME) treatment systems that require large footprint, long HRT and fail to meet the Malaysian Department of Environment (DOE) discharge limit. Hence, the current research is aimed to design a novel integrated anaerobic–aerobic bioreactor (IAAB) for POME treatment in order to overcome these shortcomings of the conventional system. IAAB is a new bioreactor configuration which integrates anaerobic and aerobic digestion in one reactor. The overall removal efficiencies in steady state condition in terms of chemical oxygen demand (COD), biochemical oxygen demand (BOD) and total suspended solids (TSS) were more than 99% at the organic loading rate (OLR) of 10.5g COD/Lday with methane yield of 0.24LCH4/g COD removed. The effluent quality remained stable (BOD<70mg/L) and complied with the discharge limit (BOD<100mg/L). Overall, the IAAB system exhibited good stability and pH adjustment was unnecessary. The results show that the IAAB achieves higher performance in terms of organic removal efficiency and methane yield at higher OLR and shorter HRT as compared to the conventional system. Further evaluations of its long-term performance are proposed for the subsequent study. [Copyright &y& Elsevier]

Abstract: This research is aimed at improving the thermophilic aerobic treatment system of anaerobically digested palm oil mill effluent (POME) through optimization of mixed liquor suspended solids (MLSS) at high concentration range for the first time besides other parameters of organic loading rate (OLR), dissolved oxygen (DO) concentrations and settling time. Chemical oxygen demand (COD), biochemical oxygen demand (BOD) and total suspended solids (TSS) removal ratios were measured as indicators of the system performance. Experimental results clearly indicate that MLSS and OLR are the crucial parameters in thermophilic aerobic treatment. Optimal COD, BOD and TSS removals up to 86%, 87% and 89%, respectively, were achieved with MLSS concentration and OLR of 27,000mg/L and 2.5gCOD/(Lday), respectively. More significantly, high MLSS concentration range which is yet to be reported was successfully applied and this has resulted in superior performance as compared to other thermophilic treatment studies. No significant improvement of the treatment efficiency was attained with DO concentration exceeding 5mg/L and settling time up to 24h. Hence, operation at DO concentration of 2mg/L and settling time of 2h gives a good compromise between effluent quality and system operating costs. [Copyright &y& Elsevier]

Background: Hyperkalaemia has been reported with high-dose trimethoprim (20 mg/kg/day) and standard-dose trimethoprim (6 mg/kg/day) plus sulfamethoxazole use. Aim: To investigate changes in plasma potassium concentrations in patients prescribed standard-dose trimethoprim 300 mg daily for urinary tract infections. Method: A retrospective cohort study of hospital patients with urinary tract infections treated with trimethoprim or other antibacterials (control group) for more than 5 days. Plasma potassium concentration, creatinine and urea were compared at baseline and at the completion of treatment. Results: There were 31 patients in the trimethoprim group and 65 patients in the control group. End-of-therapy mean plasma potassium concentrations increased significantly from baseline in the trimethoprim group (4.2 ± 0.4 mmol/L to 4.5 ± 0.5 mmol/L; p = 0.002) but not in the control group. End-of- therapy mean plasma potassium concentrations were also higher in the trimethoprim group (4.5 ± 0.5 mmol/L vs 4.2 ± 0.5 mmol/L; p = 0.007). 65% of the trimethoprim group developed end-of-therapy hyperkalaemia versus 39% of the control group. Mean creatinine concentration in the trimethoprim group increased by an average of 21% from baseline but did not change in the control group. The trimethoprim group showed no change in mean urea concentration but a decrease was noted in the control group. Conclusion: Treating urinary tract infections with trimethoprim 300 mg daily for more than 5 days was associated with an increase in plasma potassium concentration. [ABSTRACT FROM AUTHOR]

The production of highly polluting palm oil mill effluent (POME) has resulted in serious environmental hazards. While anaerobic digestion is widely accepted as an effective method for the treatment of POME, anaerobic treatment of POME alone has difficulty meeting discharge limits due to the high organic strength of POME. Hence, subsequent post-treatment following aerobic treatment is vital to meet the discharge limits. The objective of the present study is to investigate the aerobic treatment of anaerobically digested POME by using a sequencing batch reactor (SBR). The SBR performance was assessed by measuring Chemical Oxygen Demand (COD), Biochemical Oxygen Demand (BOD) and Total Suspended Solids (TSS) removal as well as Sludge Volume Index (SVI). The operating pH and dissolved oxygen concentrations were found to be 8.25–9.14 and 1.5–6.4mg/L, respectively, throughout the experiment. The experimental results demonstrate that MLVSS, OLR and sludge loading rate (SLR) play a significant role in the organic removal efficiency of SBR systems and therefore, further investigation on these parameters was conducted to attain optimum SBR performance. Maximum COD (95–96%), BOD (97–98%) and TSS (98–99%) removal efficiencies were achieved at optimum OLR, SLR and MLVSS concentration ranges of 1.8–4.2kgCOD/m3 day, 2.5–4.6kgTSS/m3 day and 22,000–25,000mg/L, respectively. The effluent quality remained stable and complied with the discharge limit. At the same time, the sludge showed good settling properties with average SVI of 65. It is envisaged that the SBR process could complement the anaerobic treatment to produce final treated effluent which meets the discharge limit. [Copyright &y& Elsevier]

Background: Scabies is a parasitic skin infestation caused by the burrowing mite Sarcoptes scabiei. It is common worldwide and spreads rapidly under crowded conditions, such as those found in socially disadvantaged communities of Indigenous populations and in developing countries. Pruritic scabies lesions facilitate opportunistic bacterial infections, particularly Group A streptococci. Streptococcal infections cause significant sequelae and the increased community streptococcal burden has led to extreme levels of acute rheumatic fever and rheumatic heart disease in Australia's Indigenous communities. In addition, emerging resistance to currently available therapeutics emphasizes the need to identify potential targets for novel chemotherapeutic and/or immunological intervention. Scabies research has been severely limited by the availability of parasites, and scabies remains a truly neglected infectious disease. We report development of a tractable model for scabies in the pig, Sus domestica. Methodology/Principal Findings: Over five years and involving ten independent cohorts, we have developed a protocol for continuous passage of Sarcoptes scabiei var. suis. To increase intensity and duration of infestation without generating animal welfare issues we have optimised an immunosuppression regimen utilising daily oral treatment with 0.2mg/kg dexamethasone. Only mild, controlled side effects are observed, and mange infection can be maintained indefinitely providing large mite numbers (>6000 mites/g skin) for molecular-based research on scabies. In pilot experiments we explore whether any adaptation of the mite population is reflected in genetic changes. Phylogenetic analysis was performed comparing sets of genetic data obtained from pig mites collected from naturally infected pigs with data from pig mites collected from the most recent cohort. Conclusions/Significance: A reliable pig/scabies animal model will facilitate in vivo studies on host immune responses to scabies including the relations to the associated bacterial pathogenesis and more detailed studies of molecular evolution and host adaption. It is a most needed tool for the further investigation of this important and widespread parasitic disease. Author Summary: Scabies, a neglected parasitic disease caused by the microscopic mite Sarcoptes scabiei, is a major driving force behind bacterial skin infections in tropical settings. Aboriginal and Torres Strait Islander peoples are nearly twenty times more likely to die from acute rheumatic fever and rheumatic heart disease than individuals from the wider Australian community. These conditions are caused by bacterial pathogens such as Group A streptococci, which have been linked to underlying scabies infestations. Community based initiatives to reduce scabies and associated disease have expanded, but have been threatened in recent years by emerging drug resistance. Critical biological questions surrounding scabies remain unanswered due to a lack of biomedical research. This has been due in part to a lack of either a suitable animal model or an in vitro culture system for scabies mites. The pig/mite model reported here will be a much needed resource for parasite material and will facilitate in vivo studies on host immune responses to scabies, including relations to associated bacterial pathogenesis, and more detailed studies of molecular evolution and host adaptation. It represents the missing tool to extrapolate emerging molecular data into an in vivo setting and may well allow the development of clinical interventions. [ABSTRACT FROM AUTHOR]

Background: Scabies is a parasitic skin infestation caused by the burrowing mite Sarcoptes scabiei. It is common worldwide and spreads rapidly under crowded conditions, such as those found in socially disadvantaged communities of Indigenous populations and in developing countries. Pruritic scabies lesions facilitate opportunistic bacterial infections, particularly Group A streptococci. Streptococcal infections cause significant sequelae and the increased community streptococcal burden has led to extreme levels of acute rheumatic fever and rheumatic heart disease in Australia's Indigenous communities. In addition, emerging resistance to currently available therapeutics emphasizes the need to identify potential targets for novel chemotherapeutic and/or immunological intervention. Scabies research has been severely limited by the availability of parasites, and scabies remains a truly neglected infectious disease. We report development of a tractable model for scabies in the pig, Sus domestica. Methodology/Principal Findings: Over five years and involving ten independent cohorts, we have developed a protocol for continuous passage of Sarcoptes scabiei var. suis. To increase intensity and duration of infestation without generating animal welfare issues we have optimised an immunosuppression regimen utilising daily oral treatment with 0.2mg/kg dexamethasone. Only mild, controlled side effects are observed, and mange infection can be maintained indefinitely providing large mite numbers (.6000 mites/g skin) formolecular-based research on scabies. In pilot experiments we explore whether any adaptation of the mite population is reflected in genetic changes. Phylogenetic analysis was performed comparing sets of genetic data obtained from pig mites collected from naturally infected pigs with data from pig mites collected from the most recent cohort. Conclusions/Significance: A reliable pig/scabies animal model will facilitate in vivo studies on host immune responses to scabies including the relations to the associated bacterial pathogenesis and more detailed studies of molecular evolution and host adaption. It is a most needed tool for the further investigation of this important and widespread parasitic disease. [ABSTRACT FROM AUTHOR]

Background: Malaria rapid diagnostic tests (RDTs) offer significant potential to improve the diagnosis of malaria, and are playing an increasing role in malaria case management, control and elimination. Peru, along with other South American countries, is moving to introduce malaria RDTs as components of malaria control programmes supported by the Global Fund for AIDS, TB and malaria. The selection of the most suitable malaria RDTs is critical to the success of the programmes. Methods: Eight of nine microscopy positive P. falciparum samples collected in Iquitos, Peru tested negative or weak positive using HRP2-detecting RDTs. These samples were tested for the presence of pfhrp2 and pfhrp3 and their flanking genes by PCR, as well as the presence of HRP proteins by ELISA. To investigate for geographic extent of HRP-deleted parasites and their temporal occurrence a retrospective study was undertaken on 148 microscopy positive P. falciparum samples collected in different areas of the Amazon region of Peru. Findings: Eight of the nine isolates lacked the pfhrp2 and/or pfhrp3 genes and one or both flanking genes, and the absence of HRP was confirmed by ELISA. The retrospective study showed that 61 (41%) and 103 (70%) of the 148 samples lacked the pfhrp2 or pfhrp3 genes respectively, with 32 (21.6%) samples lacking both hrp genes. Conclusions: This is the first documentation of P. falciparum field isolates lacking pfhrp2 and/or pfhrp3. The high frequency and wide distribution of different parasites lacking pfhrp2 and/or pfhrp3 in widely dispersed areas in the Peruvian Amazon implies that malaria RDTs targeting HRP2 will fail to detect a high proportion of P. falciparum in malaria-endemic areas of Peru and should not be used. RDTs detecting parasite LDH or aldolase and quality microscopy should be use for malaria diagnosis in this region. There is an urgent need for investigation of the abundance and geographic distribution of these parasites in Peru and neighbouring countries. [ABSTRACT FROM AUTHOR]

Background: Accurate diagnosis is essential for prompt and appropriate treatment of malaria. While rapid diagnostic tests (RDTs) offer great potential to improve malaria diagnosis, the sensitivity of RDTs has been reported to be highly variable. One possible factor contributing to variable test performance is the diversity of parasite antigens. This is of particular concern for Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-detecting RDTs since PfHRP2 has been reported to be highly variable in isolates of the Asia-Pacific region. Methods: The pfhrp2 exon 2 fragment from 458 isolates of P. falciparum collected from 38 countries was amplified and sequenced. For a subset of 80 isolates, the exon 2 fragment of histidine-rich protein 3 (pfhrp3) was also amplified and sequenced. DNA sequence and statistical analysis of the variation observed in these genes was conducted. The potential impact of the pfhrp2 variation on RDT detection rates was examined by analysing the relationship between sequence characteristics of this gene and the results of the WHO product testing of malaria RDTs: Round 1 (2008), for 34 PfHRP2-detecting RDTs. Results: Sequence analysis revealed extensive variations in the number and arrangement of various repeats encoded by the genes in parasite populations world-wide. However, no statistically robust correlation between gene structure and RDT detection rate for P. falciparum parasites at 200 parasites per microlitre was identified. Conclusions: The results suggest that despite extreme sequence variation, diversity of PfHRP2 does not appear to be a major cause of RDT sensitivity variation. [ABSTRACT FROM AUTHOR]

A personal narrative is presented in which the author talks about her talk on China's one-child policy at London's Asia House and her encounter with Zhang Erli, a retired top official of the National Family Planning Commission.

Abstract: Anaerobic–aerobic systems have been remarkably employed in industrial and municipal wastewater treatment for many years. While previously most treatment of wastewaters have been carried out in conventional anaerobic–aerobic treatment plants, in recent years, high rate anaerobic–aerobic bioreactors have been increasingly employed for wastewaters with high chemical oxygen demand (COD). This paper provides a review of the various types of high rate anaerobic–aerobic water treatment techniques currently available including high rate bioreactors and integrated anaerobic–aerobic bioreactors. The integrated bioreactors are classified into four types, which are (i) integrated bioreactors with physical separation of anaerobic–aerobic zone, (ii) integrated bioreactors without physical separation of anaerobic–aerobic zone, (iii) anaerobic–aerobic Sequencing Batch Reactors (SBR), and (iv) combined anaerobic–aerobic culture system. The integration of aerobic and anaerobic degradation pathways in a single bioreactor is capable of enhancing the overall degradation efficiency. The merits of different integrated anaerobic–aerobic bioreactors are highlighted and comparison made to identify possible future areas of research to fully utilize these methods of wastewater treatment. The comparison demonstrates that using an integrated bioreactor with stacked configuration in treating high strength industrial wastewaters is advantageous due to minimal space requirements, low capital cost and excellent COD removal efficiencies (in excess of 83%). [Copyright &y& Elsevier]

Abstract: Boron is extensively used in the ceramic industry for enhancing mechanical strength of the tiles. The discharge of boron containing wastewater to the environment causes severe pollution problems. Boron is also dangerous for human consumption and causes organisms'' reproductive impediments if the safe intake level is exceeded. Current methods to remove boron include ion-exchange, membrane filtration, precipitation–coagulation, biological and chemical treatment. These methods are costly to remove boron from the wastewater and hence infeasible for industrial wastewater treatment. In the present research, adsorption–flocculation mechanism is proposed for boron removal from ceramic wastewater by using Palm Oil Mill Boiler (POMB) bottom ash and long chain polymer or flocculant. Ceramic wastewater is turbid and milky in color which contains 15mg/L of boron and 2000mg/L of suspended solids. The optimum operating conditions for boron adsorption on POMB bottom ash and flocculation using polymer were investigated in the present research. Adsorption isotherm of boron on bottom ash was also investigated to evaluate the adsorption capacity. Adsorption isotherm modeling was conducted based on Langmuir and Freundlich isotherms. The results show that coarse POMB bottom ash with particle size larger than 2mm is a suitable adsorbent where boron is removed up to 80% under the optimum conditions (pH=8.0, dosage=40g bottom ash/300ml wastewater, residence time=1h). The results also show that KP 1200 B cationic polymer is effective in flocculating the suspended solids while AP 120 C anionic polymer is effective in flocculating the bottom ash. The combined cationic and anionic polymers are able to clarify the ceramic wastewater under the optimum conditions (dosage of KP 1200 B cationic polymer=100mg/L, dosage of AP 120 C anionic polymer=50mg/L, mixing speed=200rpm). Under the optimum operating conditions, the boron and suspended solids concentration of the treated wastewater were reduced to 3mg/L and 5mg/L respectively, satisfying the discharge requirement by Malaysia Department of Environment (DOE). The modeling study shows that the adsorption isotherm of boron onto POMB bottom ash conformed to the Freundlich Isotherm. The proposed method is suitable for boron removal in ceramic wastewater especially in regions where POMB bottom ash is abundant. [Copyright &y& Elsevier]

Studies have revealed that losses of chromosome 4q24–25 regions are frequent in cancers including head and neck squamous cell carcinoma. Our previous comparative genomic hybridization analysis showed extensive losses of chromosome arm 4q in oral squamous cell carcinoma (OSCC).To be more precise in mapping the potential regions of allelic losses and to understand the microsatellite instability (MSI) on 4q involving in oral pathogenesis, we performed allelotypings using eight polymorphic markers. Microsatellite analyses were first performed on 100 randomly selected controls to confirm the high informative rates of markers. Twenty OSCC tissues were microdissected from surgical specimens for microsatellite alterations (MA) analysis.MA was observed in 95% OSCC cases. The most eminently altered locus was 4q13.1 (75%), followed by 4q22.2 and 4q32.1 (55%). Allelic losses also occurred most frequently on these loci. Thirty-five percent cases had MA spanning 4q13.1 to 4q21.1. MSI occurred in 35% OSCC, at a lesser extent compared with allelic losses. The most common locus for MSI was 4q21.2 (20%). In addition, 4q MSI was significantly associated with the lymph node metastasis of OSCC (P = 0.01). So far, most tumor suppressor genes on 4q have not been specified.Our results were additive to previous findings and proposed novel scenario of suppressor loci located at 4q13.1–21.1 whose inactivation could be important for progression of OSCC.J Oral Pathol Med(2005)34: 209–13 [ABSTRACT FROM AUTHOR]

Lymphangiogenesis, the formation of new lymphatic vessels from pre-existing vasculature, plays critical roles in disease, including in cancer metastasis and chronic inflammation. Preclinical and recent clinical studies have now demonstrated therapeutic utility for several anti-lymphangiogenic agents, but optimal agents and efficacy in different settings remain to be determined. We tested the anti-lymphangiogenic property of 3,4-Difluorobenzocurcumin (CDF), which has previously been implicated as an anti-cancer agent, using zebrafish embryos and cultured vascular endothelial cells. We used transgenic zebrafish labelling the lymphatic system and found that CDF potently inhibits lymphangiogenesis during embryonic development. We also found that the parent compound, Curcumin, does not inhibit lymphangiogenesis. CDF blocked lymphatic and venous sprouting, and lymphatic migration in the head and trunk of the embryo. Mechanistically, CDF impaired VEGFC-VEGFR3-ERK signalling in vitro and in vivo. In an in vivo pathological model of Vegfc-overexpression, treatment with CDF rescued endothelial cell hyperplasia. CDF did not inhibit the kinase activity of VEGFR3 yet displayed more prolonged activity in vivo than previously reported kinase inhibitors. These findings warrant further assessment of CDF and its mode of action as a candidate for use in metastasis and diseases of aberrant lymphangiogenesis. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Fifty years since its inception, Light's criteria have aided in classifying pleural effusions (PEs) as exudates if 1 or more criteria are met. Thoracic ultrasound (US) emerges as a non‐invasive technique for point of care use especially if pleural procedures are contemplated.We aimed to develop a score based on radiological and US features that could separate exudates from transudates without serum and pleural fluid biochemical tests necessary for Light's criteria.A prospective review of consecutive patients with PE who underwent thoracocentesis was performed. CXRs were evaluated for laterality followed by US for echogenicity, pleural nodularity, thickening and septations. PE was classified as exudate or transudate according to Light's criteria and corroborated with albumin gradient. A score combining radiological and US features was developed.We recruited 201 patients with PE requiring thoracocentesis. Mean age was 64 years, 51% were females, 164 (81.6%) were exudates, and 37 (18.4%) were transudates. Assigning 1‐point for Diaphragmatic nodularity, Unilateral, Echogenicity, Pleural Thickening and Septations, DUETS ranged from 1 to 5. DUETS ≥2 indicated high likelihood for exudate (PPV 98.8%, NPV 100%) with 1% misclassification versus 6.9% using Light's criteria (p < 0.001).DUETS separated exudates from transudates with good accuracy, and could obviate paired serum and pleural fluid tests necessary for Light's criteria computation. Our study reflected real world practice where DUETS performed better than Light's criteria for PE that arose from more than one disease processes, and in the evaluation of patients with PE who have received diuretics. [ABSTRACT FROM AUTHOR]

The rapid emergence of novel multidrug-resistant organisms coupled with the slow development of new antibiotics is of great concern. With the discovery of New Delhi metallo-beta-lactamase 1 (NDM-1)-producing Klebsiella pneumoniae, clinicians are faced with problems in the treatment of infections caused by this multidrug-resistant organism. Therapeutic experiences are limited. We share our experience of the successful treatment of a febrile neutropenic patient with NDM-1-producing K. pneumoniae bacteraemia. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

Patients with severe asthma that remain uncontrolled incur significant medical burden and healthcare costs. Severe asthma is a heterogeneous airway disorder with complex pathophysiological mechanisms which can be broadly divided into type 2 (T2)-high and T2-low inflammatory pathways. Recent advances in asthma therapeutics with the advent of biologics have heralded an era of promising targeted therapy in this group of patients. The current available biologics, including anti-IgE mAb, anti-IL-5/IL-5R mAb and anti-IL-4Rα mAb, mainly target patients with an asthma endotype characterised by T2-high inflammation. While they have delivered positive outcomes in terms of reduction in exacerbations, improving lung function and quality of life, as well as reducing the dependence on oral corticosteroids, they have not functioned as the "panacea" as a significant proportion of patients do not respond completely to these targeted therapies. In addition, there is a lack of markers that can predict treatment response and clinicians are guided only by subjective asthma symptom scores. Suboptimal treatment response is common for individual patients. There has also been a dearth of effective targeted therapy for patients with T2-low asthma and treatment options remain limited for these patients. There is a pipeline of newer biologics targeting cytokines that operate at the interface between innate and adaptive immunity (e.g. IL-17A, thymic stromal lymphopoietin (TSLP), IL-25, IL-33, IL-32 and IL-36γ) with potential of modifying and reducing the severity of asthma. This commentary provides an overview of treatment with the current biologics and highlights the limitations, challenges and unmet needs in clinical management. We also summarise up-and-coming potential targets and therapeutic biologics for severe asthma. [ABSTRACT FROM AUTHOR]

Background: The prevalence rate of reflux esophagitis (RE) in Asia, including Taiwan, has increased dramatically in recent years. However, few studies have discussed on its relationship with metabolic syndrome (MetS). This study aimed to evaluate the correlation between RE and MetS and its components.Methods: We conducted a cross-sectional study during 2013 to 2014 in Taiwan. A total of 4895 subjects who completed upper gastrointestinal endoscopy at the Health Examination Center of Changhua Christian Hospital were enrolled. RE was defined according to the upper gastrointestinal endoscopic findings and MetS was defined according to the Taiwanese criteria. Univariate and multivariate logistic regression analyses were applied to calculate odds ratios and 95% confidence intervals for each variable to assess the associated features for RE. We analyzed the relationship between the number of MetS components and the severity of RE using the chi-square test for trend.Results: The prevalence rates of MetS and RE were respectively 28.5 and 59.6%. According to univariate logistic regression analysis, MetS was significantly associated with RE and remained a positive association in multivariate logistic regression analysis (adjusted ORß = 1.251; 95% CI = 1.071-1.462; p = 0.005). Furthermore, among the five MetS components, elevated blood pressure (adjusted ORγ = 1.163; 95% CI = 1.023-1.323; p = 0.021), abdominal obesity (adjusted ORγ = 1.173; 95% CI = 1.020-1.349; p = 0.026) and hyperglycemia (adjusted ORγ = 1.306; 95% CI = 1.142-1.495; p < 0.001) were positively associated with the presence of RE. A weak association was also found between elevated triglycerides and RE after adjusting for age and gender (adjusted ORα = 1.171; 95% CI = 1.022-1.343; p = 0.023). Reduced high-density lipoprotein cholesterol showed no significant difference between groups with and without RE. Older age (≥65 years), male gender, higher body mass index, higher uric acid, smoking, alcohol drinking, and hiatal hernia were found to be significant associated factors for RE. In addition, a dose-response relation between the number of MetS components and the presence of RE was demonstrated in the multivariate analysis. Furthermore, we performed a trend analysis and found the severity of RE got worse as the number of MetS components increased (p < 0.001).Conclusion: This study suggests that MetS is significantly related to the presence and the severity of RE. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented in which the editors discuss various reports within the issue on topics including the development of advanced waste treatment technologies, boron removal using electrocoagulation, and work on process integration.