Lactic acid bacteria waste infusion as a source of attraction and oviposition stimulation of gravid female Aedes albopictus mosquitoes.

Aedes albopictus poses a public health risk in tropical countries and temperate countries in recent decades due to its capability to transmit various human arboviruses including dengue, yellow fever, and chikungunya. Vector control is the key for preventing transmission of these pathogenic viruses. Improving the effectiveness of currently utilized collection methods, such as ovitraps, is important for best species abundance monitoring, assessment of the threat of arbovirus transmission, and optimizing control activities. Therefore, this study aimed to assess the potential use of lactic acid bacteria (LAB) waste as an infusion-baited ovitrap for Aedes collection. The performance of overnight tap water, grass hay infusion and LAB waste infusion were compared for their ability in attracting gravid female Ae. albopictus. In this study, the LAB waste infusion was substantially more alluring to Ae. albopictus mosquitoes than the two controls grass hay infusion and tap water.

Lactic acid bacteria waste infusion as a source of attraction and oviposition stimulation of gravid female Aedes albopictus mosquitoes

@#The Plasmodium knowlesi secreted protein with an altered thrombospondin repeat (PkSPATR) is an important protein that helps in the parasite’s invasion into the host cell. This protein has been regarded as one of the potential vaccine candidates against P. knowlesi infection. This study investigates the genetic diversity and natural selection of PkSPATR gene of P. knowlesi clinical isolates from Malaysia. PCR amplification of the full length PkSPATR gene was performed on 60 blood samples of infected P. knowlesi patients from Peninsular Malaysia and Malaysian Borneo. The amplified PCR products were cloned and sequenced. Sequence analysis of PkSPATR from Malaysia showed higher nucleotide diversity (CDS p: 0.01462) than previously reported Plasmodium vivax PvSPATR (p = 0.0003). PkSPATR from Peninsular Malaysia was observed to have slightly higher diversity (CDS p: 0.01307) than those from Malaysian Borneo (CDS p: 0.01212). Natural selection analysis on PkSPATR indicated significant purifying selection. Multiple amino acid sequence alignment revealed 69 polymorphic sites. The phylogenetic tree and haplotype network did not show any distinct clustering of PkSPATR. The low genetic diversity level, natural selection and absence of clustering implied functional constrains of the PkSPATR protein.

Development, Validation and Field Evaluation of the Singapore Longitudinal Ageing Study (SLAS) Risk Index for Prediction of Mild Cognitive Impairment and Dementia.

BACKGROUND: Mild cognitive impairment (MCI) is a critical pre-dementia target for preventive interventions. There are few brief screening tools based on self-reported personal lifestyle and health-related information for predicting MCI that have been validated for their generalizability and utility in primary care and community settings. OBJECTIVE: To develop and validate a MCI risk prediction index, and evaluate its field application in a pilot community intervention trial project. DESIGN: Two independent population-based cohorts in the Singapore Longitudinal Ageing Study (SLAS). We used SLAS1 as a development cohort to construct the risk assessment instrument, and SLA2 as a validation cohort to verify its generalizability. SETTING: community-based screening and lifestyle intervention Participants: (1) SLAS1 cognitively normal (CN) aged ≥55 years with average 3 years (N=1601); (2) SLAS2 cohort (N=3051) with average 4 years of follow up. (3) 437 participants in a pilot community intervention project. MEASUREMENTS: The risk index indicators included age, female sex, years of schooling, hearing loss, depression, life satisfaction, number of cardio-metabolic risk factors (wide waist circumference, pre-diabetes or diabetes, hypertension, dyslipidemia). Weighted summed scores predicted probabilities of MCI or dementia. A self-administered questionnaire field version of the risk index was deployed in the pilot community project and evaluated using pre-intervention baseline cognitive function of participants. RESULTS: Risk scores were associated with increasing probabilities of progression to MCI-or-dementia in the development cohort (AUC=0.73) and with increased prevalence and incidence of MCI-or-dementia in the validation cohort (AUC=0.74). The field questionnaire risk index identified high risk individuals with strong correlation with RBANS cognitive scores in the community program (p<0.001). CONCLUSIONS: The SLAS risk index is accurate and replicable in predicting MCI, and is applicable in community interventions for dementia prevention.

Nutritional Status and Risks of Cognitive Decline and Incident Neurocognitive Disorders: Singapore Longitudinal Ageing Studies.

BACKGROUND: Studies suggest that nutritional interventions using the whole diet approach such as the Mediterranean diet may delay cognitive decline and dementia onset. However, substantial numbers of older adults are non-adherent to any ideally healthy dietary pattern and are at risk of malnutrition. OBJECTIVE: The present study investigated the relationship between global malnutrition risk and onsets of cognitive decline and neurocognitive disorders (NCD), including mild cognitive impairment (MCI) or dementia in community-dwelling older adults. METHODS: Participants aged ≥ 55 years in the Singapore Longitudinal Ageing Studies (SLAS) were assessed at baseline using the Elderly Nutritional Indicators for Geriatric Malnutrition Assessment (ENIGMA) and followed up 3-5 years subsequently on cognitive decline (MMSE drop ≥ 2) among 3128 dementia-free individuals, and incident neurocognitive disorders (NCD) among 2640 cognitive normal individuals. RESULTS: Individuals at high nutritional risk score (≥ 3) were more likely to develop cognitive decline (OR=1.42, 95%CI=1.01-1.99) and incident MCI-or-dementia (OR=1.64, 95%CI=1.03-2.59), controlling for age, sex, ethnicity, low education, APOE-e4, hearing loss, physical, social, and mental activities, depressive symptoms, smoking, alcohol, central obesity, hypertension, diabetes, low HDL, high triglyceride, cardiac disease, and stroke. Among ENIGMA component indicators, low albumin at baseline was associated with cognitive decline and incident NCD, and 5 or more drugs used, few fruits/vegetables/milk products daily, and low total cholesterol were associated with incident NCD. CONCLUSION: The ENIGMA measure of global malnutrition risk predicts cognitive decline and incident neurocognitive disorders, suggesting the feasibility of identifying vulnerable subpopulations of older adults for correction of malnutrition risk to prevent neurocognitive disorders.

Chimeric Murine Polyomavirus Virus-Like Particles Induce Plasmodium Antigen-Specific CD8+ T Cell and Antibody Responses.

An effective vaccine against the Plasmodium parasite is likely to require the induction of robust antibody and T cell responses. Chimeric virus-like particles are an effective vaccine platform for induction of antibody responses, but their capacity to induce robust cellular responses and cell-mediated protection against pathogen challenge has not been established. To evaluate this, we produced chimeric constructs using the murine polyomavirus structural protein with surface-exposed CD8+ or CD4+ T cell or B cell repeat epitopes derived from the Plasmodium yoelii circumsporozoite protein, and assessed immunogenicity and protective capacity in a murine model. Robust CD8+ T cell responses were induced by immunization with the chimeric CD8+ T cell epitope virus-like particles, however CD4+ T cell responses were very low. The B cell chimeric construct induced robust antibody responses but there was no apparent synergy when T cell and B cell constructs were administered as a pool. A heterologous prime/boost regimen using plasmid DNA priming followed by a VLP boost was more effective than homologous VLP immunization for cellular immunity and protection. These data show that chimeric murine polyomavirus virus-like particles are a good platform for induction of CD8+ T cell responses as well as antibody responses.

Symptom clusters of subjective cognitive decline amongst cognitively normal older persons and their utilities in predicting objective cognitive performance: structural equation modelling.

BACKGROUND AND PURPOSE: Prior literature on subjective cognitive decline (SCD) has mostly focused on memory complaints. It is uncertain whether the other non-memory complaints are equally relevant and can be used, alongside memory complaints, to identify populations at high risk of cognitive impairment. How the memory and non-memory complaints of SCD cluster with each other amongst community-dwelling individuals was investigated, and the differential utility of the symptom clusters of SCD in predicting objective cognitive performance was evaluated. METHODS: This study included 736 participants who were ≥60 years and had normal cognition, using the baseline data of an ongoing cohort study. Participants completed baseline assessments which comprised an SCD scale, a global cognitive measure and neuropsychological tests. Symptom clusters of SCD - as identified from exploratory and confirmatory factor analyses - were included in structural equation models to predict baseline changes in neuropsychological tests. RESULTS: The symptoms of SCD were split into two distinct factors, of which factor 1 was reported much more frequently than factor 2. Each standard deviation (SD) increment in factor 1 led to a 0.16-0.50 SD increase in global cognition, immediate memory, visuospatial abilities, language, attention and delayed memory (P < 0.05). In contrast, each SD increment in factor 2 worsened some of the cognitive domains by 0.18-0.37 SD. CONCLUSIONS: The various complaints of SCD can have different implications amongst cognitively normal older persons and may possibly be classified into age-related symptoms and pathological symptoms. The findings highlight the need for caution when selecting SCD measures, and illustrate the potential utility of SCD subtypes to inform on the underlying neurobiology.

Author Correction: Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement.

The original version of this Article omitted the author Kuan Wang, who is from the 'College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan' and 'Nanyang Environment & Water Research Institute, Nanyang Technological University, Singapore 637141, Singapore.'Also, the author S.H. Lim was incorrectly given as L.S. Hoi and A. Larsson was incorrectly given as A. Larson.The "Author contributions" was amended to reflect the authorship changes. It previously read 'Y.Z.S., C.-W.Q., and A.Q.L. jointly conceived the idea. Y.Z.S., S.X., Y.Z., J.B.Z., W.S., J.H.W., T.N.C., Z.C.Y., Y.L.H., B.L., P.H.Y., D.P.T., and C.-W.Q. performed the numerical simulations and theoretical analysis. Y.Z.S., S.X., and L.K.C. did the fabrication and experiments of particle hopping, biomolecule binding and flow cytometry. A.L. and L.S.H. did the SPR experiments. S.X., Y.Z.S., Y.Z., C.-W.Q., Y.-Y.C., L.K.C., T.H.Z., and A.Q.L. prepared the manuscript. S.X., Y.Z., C.-W.Q., and A.Q.L. supervised and coordinated all the work. All authors commented on the manuscript.' The correct version states 'B.L., K. W., P.H.Y.' instead of 'B.L., P.H.Y.' and 'S.H.L.' in place of 'L.S.H.'This has been corrected in both the PDF and HTML versions of the Article.

The Changing Profile of Patients in a Geriatric Medicine Led Memory Clinic over 12 Years.

OBJECTIVES: Memory clinics play an important role in enabling early dementia diagnosis and intervention. Few studies have investigated the changing patient profiles at memory clinics over time. We studied the trend of patient characteristics in a geriatric medicine-led memory clinic over 12 years to improve services and care to meet their needs. SETTING AND PARTICIPANTS: Data from 2340 first-visit patients seen at a memory clinic from 2005-2017 were extracted from a registered database and analysed. DESIGN: ANOVA, Pearson chi-square and non-parametric tests were used to describe and compare between patients with dementia (PWD) and patients with no dementia (PND). MEASUREMENTS: Data included diagnoses of dementia and mild cognitive impairment, age, education, MMSE scores and comorbidities. RESULTS: Patients averaged 77.2 ± 8.3 years of age with mean MMSE score of 16.2 ± 6.7. Those diagnosed with dementia were older (78.3 ± 7.9 years) and almost half (48.4%) had moderate or moderately severe dementia (FAST 5-6). Over time, there was a growing proportion of patients with mild cognitive impairment (MCI) and mild Alzheimer's dementia. Many PWD had co-morbidities of hypertension (65.9%), hyperlipidemia (55.1%), diabetes (33.5%) and 28.4% were frail. CONCLUSIONS: The findings call for services to better diagnose and manage patients at the earlier stages of cognitive impairment and provide holistic interventions for those with frailty and other co-morbidities. The continued rise in number of patients presenting to memory clinics provides impetus to expedite integration of tertiary-based memory clinics with primary and community care providers to better support PWD and their families.

Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement.

Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer's theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level.

Multi-Domains Lifestyle Interventions Reduces Depressive Symptoms among Frail and Pre-Frail Older Persons: Randomized Controlled Trial.

BACKGROUND: We investigated the effect of multi-domain lifestyle (physical, nutritional, cognitive) interventions among frail and pre-frail community-living older persons on reducing depressive symptoms. METHOD: Participants aged 65 and above were randomly allocated to 24 weeks duration interventions with nutritional supplementation (N=49), physical training (N=48), cognitive training (N=50), combination intervention (N=49) and usual care control (N=50). Depressive symptoms were assessed by the Geriatric Depression Scale (GDS-15) at baseline (0M), 3 month (3M), 6 month (6M) and 12 month (12M). RESULTS: Mean GDS scores in the control group increased from 0.52 (0M) and 0.54 (3M) to 0.74 (6M), and 0.83 (12M). Compared to the control group, interventions showed significant differences (∆=change) at 6M for cognitive versus control (∆=-0.39, p=0.021, group*time interaction p=0.14); physical versus control (∆ =-0.37, p=0.026, group*time interaction p=0.13), and at 12M for nutrition versus control (∆ =-0.46, p=0.016, group*time interaction p=0.15). The effect for combination versus control was significant at 6M (∆ =-0.43, p=0.020) and 12M (∆ =-0.51, p=0.005, group*time interaction p=0.026). Estimated 12-month cumulative incidence of depressive symptoms (GDS≥2) relative to control were OR=0.38, p=0.037 (nutrition); OR=0.71, p=0.40 (cognitive); OR=0.39, p=0.042 (physical training) and OR=0.38, p=0.037 (combination). Changes in gait speed and energy level were significantly associated with changes in GDS scores over time. CONCLUSION: Multi-domain interventions that reverse frailty among community-living older persons also reduce depressive symptomatology. Public health education and programmatic measures combining nutritional, physical and cognitive interventions for at-risk frail older people may likely benefit psychological wellbeing.

High-resolution and multi-range particle separation by microscopic vibration in an optofluidic chip.

An optofluidic chip is demonstrated in experiments for high-resolution and multi-range particle separation through the optically-induced microscopic vibration effect, where nanoparticles are trapped in loosely overdamped optical potential wells created with combined optical and fluidic constraints. It is the first demonstration of separating single nanoparticles with diameters ranging from 60 to 100 nm with a resolution of 10 nm. Nanoparticles vibrate with an amplitude of 3-7 µm in the loosely overdamped potential wells in the microchannel. The proposed optofluidic device is capable of high-resolution particle separation at both nanoscale and microscale without reconfiguring the device. The separation of bacteria from other larger cells is accomplished using the same chip and operation conditions. The unique trapping mechanism and the superb performance in high-resolution and multi-range particle separation of the proposed optofluidic chip promise great potential for a diverse range of biomedical applications.

Correction: Optofluidic lens with low spherical and low field curvature aberrations.

Correction for 'Optofluidic lens with low spherical and low field curvature aberrations' by H. T. Zhao et al., Lab Chip, 2016, 16, 1617-1624.

Policy Support and Resources Mobilization for the National Schistosomiasis Control Programme in The People's Republic of China.

Schistosomiasis remains a public health problem in many developing countries around the world. After the founding of The People's Republic of China, from 1949 till date, all levels of government, from central to local, have been attaching great importance to schistosomiasis control in The People's Republic of China. With considerable policy support and resources mobilization, the national schistosomiasis control programmes have been implemented during the past 65years. Here, we summarize the successful experience of schistosomiasis control during the process. Recommendations for the future management of the Chinese national schistosomiasis elimination programme are put forward after considering the remaining challenges, shortcomings and lessons learnt from 65years of schistosomiasis control drives in The People's Republic of China. They will help to sustain past achievements, foster the attainment of the ultimate goal of schistosomiasis elimination for the country and provide reference for schistosomiasis control programme in other countries.

Optofluidic lens with low spherical and low field curvature aberrations.

This paper reports an optofluidic lens with low spherical and low field curvature aberrations through the desired refractive index profile by precisely controlling the mixing between ethylene glycol and deionized water in an optofluidic chip. The experimental results demonstrate that the spherical aberration is reduced to 19.5 µm and the full width at half maximum of the focal point is 7.8 µm with a wide divergence angle of 35 degrees. In addition, the optofluidic lens can focus light at different off-axis positions on the focal plane with Δx' < 6.8 µm and at opposite transverse positions with |Δy - Δy'| < 5.7 µm. This is the first demonstration of a special optofluidic lens that significantly reduces both the spherical and field curvature aberrations, which enhances the focusing power and facilitates multiple light source illumination using a single lens. It is anticipated to have high potential for applications such as on-chip light manipulation, sample illumination and multiplexed detection.

Cell refractive index for cell biology and disease diagnosis: past, present and future.

Cell refractive index is a key biophysical parameter, which has been extensively studied. It is correlated with other cell biophysical properties including mechanical, electrical and optical properties, and not only represents the intracellular mass and concentration of a cell, but also provides important insight for various biological models. Measurement techniques developed earlier only measure the effective refractive index of a cell or a cell suspension, providing only limited information on cell refractive index and hence hindering its in-depth analysis and correlation. Recently, the emergence of microfluidic, photonic and imaging technologies has enabled the manipulation of a single cell and the 3D refractive index of a single cell down to sub-micron resolution, providing powerful tools to study cells based on refractive index. In this review, we provide an overview of cell refractive index models and measurement techniques including microfluidic chip-based techniques for the last 50 years, present the applications and significance of cell refractive index in cell biology, hematology, and pathology, and discuss future research trends in the field, including 3D imaging methods, integration with microfluidics and potential applications in new and breakthrough research areas.

Delineation of clinical features in Wiedemann-Steiner syndrome caused by KMT2A mutations.

Wiedemann-Steiner syndrome (WSS) is an autosomal dominant congenital anomaly syndrome characterized by hairy elbows, dysmorphic facial appearances (hypertelorism, thick eyebrows, downslanted and vertically narrow palpebral fissures), pre- and post-natal growth deficiency, and psychomotor delay. WSS is caused by heterozygous mutations in KMT2A (also known as MLL), a gene encoding a histone methyltransferase. Here, we identify six novel KMT2A mutations in six WSS patients, with four mutations occurring de novo. Interestingly, some of the patients were initially diagnosed with atypical Kabuki syndrome, which is caused by mutations in KMT2D or KDM6A, genes also involved in histone methylation. KMT2A mutations and clinical features are summarized in our six patients together with eight previously reported patients. Furthermore, clinical comparison of the two syndromes is discussed in detail.

Preliminary results of using inertial sensors to detect dementia- related wandering patterns.

We present a solution for detecting dementia-related travel patterns using only inertial sensors. The results and lessons learnt from the experiments on dementia and non-dementia subjects are reported.

Energetic changes caused by antigenic module insertion in a virus-like particle revealed by experiment and molecular dynamics simulations.

The success of recombinant virus-like particles (VLPs) for human papillomavirus and hepatitis B demonstrates the potential of VLPs as safe and efficacious vaccines. With new modular designs emerging, the effects of antigen module insertion on the self-assembly and structural integrity of VLPs should be clarified so as to better enabling improved design. Previous work has revealed insights into the molecular energetics of a VLP subunit, capsomere, comparing energetics within various solution conditions known to drive or inhibit self-assembly. In the present study, molecular dynamics (MD) simulations coupled with the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method were performed to examine the molecular interactions and energetics in a modular capsomere of a murine polyomavirus (MPV) VLP designed to protect against influenza. Insertion of an influenza antigenic module is found to lower the binding energy within the capsomere, and a more active state is observed in Assembly Buffer as compared with that in Stabilization Buffer, which has been experimentally validated through measurements using differential scanning calorimetry. Further in-depth analysis based on free-energy decomposition indicates that destabilized binding can be attributed to electrostatic interaction induced by the chosen antigen module. These results provide molecular insights into the conformational stability of capsomeres and their abilities to be exploited for antigen presentation, and are expected to be beneficial for the biomolecular engineering of VLP vaccines.