Comprehensive cardiopulmonary profile of individuals with Down syndrome.

BACKGROUND: Individuals with Down syndrome (DS) have low levels of cardiorespiratory fitness and previous studies have shown that these low levels of fitness have a physiological cause. During exercise, the cardiovascular, ventilatory and muscular systems are simultaneously active. While individual parameters of these systems have been investigated in DS before, the interaction between these parameters and systems have not been discussed in detail. Doing so may provide important insight regarding the aetiology of low cardiorespiratory fitness and which parameters of the cardiovascular, pulmonary and muscular systems are altered in individuals with DS compared with their peers without DS. METHODS: Cardiopulmonary exercise tests were performed in healthy adults with and without DS. Parameters related to the cardiovascular, ventilatory and muscular systems were collected until VO2peak . In total, 51 participants were included in analysis, of which 21 had DS. RESULTS: Individuals with DS showed lower peak values for all collected outcomes (P ≤ 0.001) compared with those without DS, except for ventilatory threshold as a percentage of maximal oxygen uptake and VE /VCO2 slope, which were similar. CONCLUSIONS: Our results show that individuals with DS present impairments across the cardiovascular, ventilatory and muscular aspects of the cardiopulmonary system.

Impact of food texture modifications on oral processing behaviour, bolus properties and postprandial glucose responses.

Several studies have demonstrated food texture manipulation on oral processing behaviour (OPB). We explored the effect of texture-differences of equivalent carbohydrate load on OPB, bolus properties and postprandial glycaemic responses (PPG). In a randomised cross-over, within-subjects, non-blinded design, healthy male participants (N = 39) consumed fixed portions of white rice (WR) and rice cake (RC) while being video recorded to measure microstructural eating behaviours. PPG was compared between test foods over a period of 120-min, and the bolus properties and saliva uptake at swallow were measured for both test foods. RC displayed higher instrumental hardness, chewiness and Young's modulus than WR (p = 0.01), and participants perceived RC as more springy and sticky than WR (p < 0.001). The RC meal was chewed more per bite (p < 0.001) and consumed at a faster eating rate (p = 0.033) than WR. WR bolus particles were smaller at swallow (p < 0.001) with a larger total surface area (p < 0.001), compared to RC. The glucose response for RC was significantly higher during the first 30-min postprandial period (p = 0.010), and lower in the later (30-120 min) postprandial period (p = 0.031) compared to WR. Total blood glucose iAUC did not differ significantly between WR and RC meals despite their large differences in texture, OPB and bolus properties. Oro-sensory exposure time was a significant predictor of glucose iAUC30min for both test meals (RC, p = 0.003; WR, p = 0.029). Saliva uptake in the bolus was significantly positively associated with blood glucose during the first 30-min postprandial period for the RC meal (p = 0.008), but not for WR. We conclude that food texture modifications can influence OPB and bolus properties which are key contributors to the dynamic evolution of the glycaemic response. Total blood glucose responses were the same for both test foods, though differences in oral processing and bolus properties influenced temporal changes in PPG.

Obesity Measures and Definitions of Sarcopenic Obesity in Singaporean Adults - the Yishun Study.

OBJECTIVES: Due to the lack of a uniform obesity definition, there is marked variability in reported sarcopenic obesity (SO) prevalence and associated health outcomes. We compare the association of SO with physical function using current Asian Working Group for Sarcopenia (AWGS) guidelines and different obesity measures to propose the most optimal SO diagnostic formulation according to functional impairment, and describe SO prevalence among community-dwelling young and old adults. DESIGN: Obesity was defined according to waist circumference (WC), percentage body fat (PBF), fat mass index (FMI), fat mass/fat-free mass ratio (FM/FFM), or body mass index (BMI). SO was defined as the presence of both obesity and AWGS sarcopenia. Muscle function was compared among phenotypes and obesity definitions using ANOVA. Differences across obesity measures were further ascertained using multiple linear regressions to determine their associations with the Short Physical Performance Battery (SPPB). SETTING: Community-dwelling adults 21 years old and above were recruited from a large urban residential town in Singapore. PARTICIPANTS: 535 community-dwelling Singaporeans were recruited (21-90 years old, 57.9% women), filling quotas of 20-40 participants in each sex- and age-group. MEASUREMENTS: We took measurements of height, weight, BMI, waist and hip circumferences, body fat, muscle mass, muscle strength, and functional assessments. Questionnaire-based physical and cognitive factors were also assessed. RESULTS: Overall prevalence of SO was 7.6% (WC-based), 5.1% (PBF-based), 2.7% (FMI-based), 1.5% (FM/FFM-based), and 0.4% (BMI-based). SO was significantly associated with SPPB only in the FMI model (p<0.05), and total variance explained by the different regression models was highest for the FMI model. CONCLUSIONS: Our findings suggest FMI as the most preferred measure for obesity and support its use as a diagnostic criteria for SO.

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.

Malnutrition and Sarcopenia in Community-Dwelling Adults in Singapore: Yishun Health Study.

OBJECTIVES: To determine the overlapping prevalence of malnutrition and sarcopenia and the association between parameters of malnutrition with muscle mass and strength in a community-dwelling Singaporean adult population. DESIGN: This was a cross-sectional study. SETTING: Large north-eastern residential town of Yishun in Singapore. PARTICIPANTS: Random sampling of community-dwelling Singaporeans aged 21-90 years old (n=541). MEASUREMENTS: Anthropometry, body composition and handgrip strength (muscle strength) were measured. Sarcopenia was identified using dual-energy x-ray absorptiometry scan (muscle mass). Nutritional status was measured using Mini Nutritional Assessment (MNA-SF). Other questionnaires collected included physical activity and cognition. Associations between nutritional status with sarcopenia as well as with muscle mass and strength were analysed using multinomial logistics and linear regressions. RESULTS: The overall population-adjusted prevalence of those at nutritional risk and malnourished were 18.5% and 0.1% respectively. More than a third of participants (35%) who were at nutritional risk were sarcopenic. Malnourished participants were all sarcopenic (100%, N=2) whereas those who were sarcopenic, 27.0% (N=37) were at nutritional risk/malnourished. Being at nutritional risk/malnourished was significantly associated with 2 to 3 times increased odds of sarcopenia in multivariate analyses adjusting for age, gender, physical activity level and cognition, and fat mass index. Favourable MNA parameter scores on food intake and BMI were positively associated with greater muscle mass and handgrip strength (p<0.05). CONCLUSION: Given the overlapping clinical presentation of malnutrition and sarcopenia, community screening protocols should include combination screening of nutritional status and sarcopenia with appropriate interventions to mitigate risk of adverse health outcomes.

Targeting the Id1-Kif11 Axis in Triple-Negative Breast Cancer Using Combination Therapy.

The basic helix-loop-helix (bHLH) transcription factors inhibitor of differentiation 1 (Id1) and inhibitor of differentiation 3 (Id3) (referred to as Id) have an important role in maintaining the cancer stem cell (CSC) phenotype in the triple-negative breast cancer (TNBC) subtype. In this study, we aimed to understand the molecular mechanism underlying Id control of CSC phenotype and exploit it for therapeutic purposes. We used two different TNBC tumor models marked by either Id depletion or Id1 expression in order to identify Id targets using a combinatorial analysis of RNA sequencing and microarray data. Phenotypically, Id protein depletion leads to cell cycle arrest in the G0/G1 phase, which we demonstrate is reversible. In order to understand the molecular underpinning of Id proteins on the cell cycle phenotype, we carried out a large-scale small interfering RNA (siRNA) screen of 61 putative targets identified by using genomic analysis of two Id TNBC tumor models. Kinesin Family Member 11 (Kif11) and Aurora Kinase A (Aurka), which are critical cell cycle regulators, were further validated as Id targets. Interestingly, unlike in Id depletion conditions, Kif11 and Aurka knockdown leads to a G2/M arrest, suggesting a novel Id cell cycle mechanism, which we will explore in further studies. Therapeutic targeting of Kif11 to block the Id1-Kif11 axis was carried out using small molecular inhibitor ispinesib. We finally leveraged our findings to target the Id/Kif11 pathway using the small molecule inhibitor ispinesib in the Id+ CSC results combined with chemotherapy for better response in TNBC subtypes. This work opens up exciting new possibilities of targeting Id targets such as Kif11 in the TNBC subtype, which is currently refractory to chemotherapy. Targeting the Id1-Kif11 molecular pathway in the Id1+ CSCs in combination with chemotherapy and small molecular inhibitor results in more effective debulking of TNBC.

Interictal hemodynamic abnormality during motor activation in sporadic hemiplegic migraine: An explorative study.

INTRODUCTION: The motor weakness in sporadic hemiplegic migraine (SHM) is a poorly understood aura manifestation. Cortical spreading depression affecting motor excitability and alterations of neurovascular coupling may be integral to the development of migraine aura. METHODS: We studied 10 right-handed SHM patients and 17 healthy controls with functional near-infrared spectroscopy (fNIRS) in the interictal period. Subjects performed a finger opposition task and had real time determination of oxyhemoglobin (OxyHb) and deoxyhemoglobin (deOxyHb) changes. Recordings were completed with 10 left and 10 right sided cortical channels. RESULTS: Mean baseline to peak changes were significantly reduced in SHM patients as compared to controls bilaterally only for OxyHb measurements in the anteromedial channels. Mean time to peak changes were significant delayed in SHM patients compared to controls bilaterally largely for OxyHb measurements in the posterolateral channels, with the exception of 2 recording channels. CONCLUSIONS: Our findings suggest presence of abnormal interictal hemodynamic responses to increased metabolic demands during motor activation in SHM. These bilateral cerebrovascular changes involve OxyHb to a much larger degree than deOxyHb. Baseline to peak changes were evident more in the anteromedial channels, whereas time to peak changes were more evident in the posterolateral channels. These findings suggest that oxygen inflow into specific brain regions may be defective in SHM as opposed to oxygen utilization. Our findings suggest that in SHM, enduring hemodynamic deficits in response to an impending motor task are evident, which can be further explored in future studies, and possibly therapeutic trials.

Microcytic to hypochromic ratio as a discriminant index of thalassaemia trait in subjects with hypochromic anaemia.

INTRODUCTION: Differentiating between thalassaemia and iron deficiency anaemia (IDA) in hypochromic anaemia is a challenge to pathologists as it influences the choice of subsequent specialized confirmatory tests. In this study, we aimed to evaluate the performance of microcytic to hypochromic ratio (MicroR/ Hypo-He, M/H ratio) as a discriminant index in hypochromic anaemia. MATERIALS AND METHODS: A retrospective study was carried out on 318 subjects with hypochromic anaemia, which comprised 162 IDA and 156 thalassaemia trait subjects with α-thalassemia, ß-thalassemia and HbE trait. Optimal cut-off value, sensitivity and specificity of M/H ratio for thalassaemia trait discrimination was determined using Receiver Operating Characteristic (ROC) analysis. RESULTS: Subjects with thalassaemia trait showed higher MicroR compared to IDA ( p< 0.001) while subjects with IDA demonstrated higher Hypo-He than thalassaemia trait (p < 0.001). M/H ratio was significantly higher in thalassaemia trait compared to IDA, with medians of 3.77 (interquartile range: 2.57 - 6.52) and 1.73 (interquartile range: 1.27 - 2.38), respectively (p < 0.001). M/H ratio ≥ 2.25 was the optimal cut-off value for discriminating thalassaemia trait from IDA in hypochromic anaemia, with the area under ROC curve (AUC) of 0.83, sensitivity of 80.8% and specificity of 71.6%. CONCLUSIONS: M/H ratio is a useful discriminant index to distinguish thalassaemia trait from IDA in hypochromic anaemia prior to diagnostic analysis for thalassaemia confirmation. High M/H ratio is suggestive of thalassaemia trait than of IDA. However, more studies are required to establish the role of M/H ratio as a screening tool for thalassaemia discrimination in hypochromic anaemia.

Id Proteins Promote a Cancer Stem Cell Phenotype in Mouse Models of Triple Negative Breast Cancer via Negative Regulation of Robo1.

Breast cancers display phenotypic and functional heterogeneity and several lines of evidence support the existence of cancer stem cells (CSCs) in certain breast cancers, a minor population of cells capable of tumor initiation and metastatic dissemination. Identifying factors that regulate the CSC phenotype is therefore important for developing strategies to treat metastatic disease. The Inhibitor of Differentiation Protein 1 (Id1) and its closely related family member Inhibitor of Differentiation 3 (Id3) (collectively termed Id) are expressed by a diversity of stem cells and are required for metastatic dissemination in experimental models of breast cancer. In this study, we show that ID1 is expressed in rare neoplastic cells within ER-negative breast cancers. To address the function of Id1 expressing cells within tumors, we developed independent murine models of Triple Negative Breast Cancer (TNBC) in which a genetic reporter permitted the prospective isolation of Id1+ cells. Id1+ cells are enriched for self-renewal in tumorsphere assays in vitro and for tumor initiation in vivo. Conversely, depletion of Id1 and Id3 in the 4T1 murine model of TNBC demonstrates that Id1/3 are required for cell proliferation and self-renewal in vitro, as well as primary tumor growth and metastatic colonization of the lung in vivo. Using combined bioinformatic analysis, we have defined a novel mechanism of Id protein function via negative regulation of the Roundabout Axon Guidance Receptor Homolog 1 (Robo1) leading to activation of a Myc transcriptional programme.

Risk Factors of Progression to Frailty: Findings from the Singapore Longitudinal Ageing Study.

OBJECTIVES: To investigate risk factors of incident physical frailty. DESIGN: A population-based observational longitudinal study. SETTING: Community-dwelling elderly with age 55 years and above recruited from 2009 through 2011 in the second wave Singapore Longitudinal Ageing Study-2 (SLAS-2) were followed up 3-5 years later. PARTICIPANTS: A total of 1297 participants, mean age of 65.6 ±0.19, who were free of physical frailty. MEASUREMENTS: Incident frailty defined by three or more criteria of the physical phenotype used in the Cardiovascular Health Study was determined at follow-up. Potential risk factors assessed at baseline included demographic, socioeconomic, medical, psychological factors, and biochemical markers. RESULTS: A total of 204 (15.7%) participants, including 81 (10.87%) of the robust and 123 (22.28%) of the prefrail transited to frailty at follow-up. Age, no education, MMSE score, diabetes, prediabetes and diabetes, arthritis, ≥5 medications, fair and poor self-rated health, moderate to high nutritional risk (NSI ≥3), Hb (g/dL), CRP (mg/L), low B12, low folate, albumin (g/L), low total cholesterol, adjusted for sex, age and education, were significantly associated (p<0.05) with incident frailty. In stepwise selection models, age (year) (OR=1.07, 95%CI=1.03-1.10, p<0.001), albumin (g/L) (OR=0.85, 95%CI=0.77-0.94, p=0.002), MMSE score (OR=0.88, 95%CI=0.78-0.98, p=0.02), low folate (OR=3.72, 95%CI=1.17-11.86, p=0.03, and previous hospitalization (OR=2.26, 95%CI=1.01-5.04,p=0.05) were significantly associated with incident frailty. CONCLUSIONS: The study revealed multiple modifiable risk factors, especially related to poor nutrition, for which preventive measures and early management could potentially halt or delay the development of frailty.

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.

Nutritional and Frailty State Transitions in the Singapore Longitudinal Aging Study.

BACKGROUND: Malnutrition is a major determinant of the physical frailty syndrome. Dynamic transitions in frailty states over time is well documented, but few studies have documented temporal changes in nutritional states and whether they influence frailty outcomes. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: Community-dwelling older Singaporeans aged ≥55y with a 5-year follow-up (n=1162) in the Singapore Longitudinal Ageing Study 2 (SLAS-2). MEASUREMENTS: The Mini Nutritional Assessment Short-Form (MNA-SF) was used to determine nutritional status, and the Fried's criteria (shrinking, weakness, slowness, exhaustion and inactivity) was used to assess physical frailty phenotype at both baseline and follow-up. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were adjusted for multiple baseline co-variables. RESULTS: At baseline, being at risk of malnutrition/malnourished was associated with increased odds of prevalent pre-frailty (OR=2.76, 95% CI=1.86-4.10) and frailty (OR=4.10, 95% CI=1.41-11.9). Baseline robust individuals who were persistently at risk of malnutrition/malnourished showed an increased odds of conversion to being pre-frail/frail at follow-up (OR=3.45, 95% CI=1.00-11.9). Among baseline pre-frail/frail individuals, reversion to being robust were significantly less likely among those who were persistently at risk of malnutrition/malnourished (OR=0.26, 95% CI=0.10-0.67) and those whose baseline normal nutrition worsened at follow-up (OR=0.20, 95% CI=0.06-0.74). CONCLUSION: Changes in nutritional states are associated with frailty state transitions, and monitoring changes in nutritional status is recommended for the prevention and severity reduction of frailty among older people in the community.

Strong Relationship between Malnutrition and Cognitive Frailty in the Singapore Longitudinal Ageing Studies (SLAS-1 and SLAS-2).

BACKGROUND: Physical frailty is well known to be strongly associated with malnutrition, but the combined impact of physical frailty and cognitive impairment among non-demented older persons (cognitive frailty) on malnutrition prevalence is not well documented. DESIGN: Cross-sectional cohort study. SETTING AND PARTICIPANTS: Community-dwelling older Singaporeans aged ≥55y (n=5414) without dementia in the Singapore Longitudinal Ageing Study (SLAS-1 and SLAS-2). MEASUREMENTS: The Mini Nutritional Assessment - short form (MNA-SF) and Nutrition Screening Initiative (NSI) Determine Checklist were used to determine their nutritional status. Participants were categorized as cognitive normal (CN) or cognitive impaired (CI) by Mini Mental State Examination (MMSE<=23), as pre-frail (PF) (score=1-2) or frail (F) (score=3-5) using Fried's criteria, and as cognitive pre-frail (PF+CI) or cognitive frail (F+CI). RESULTS: The prevalence of cognitive frailty was 1.6%, and cognitive pre-frailty was 5.5% (total, 7.1%). The prevalence of MNA malnutrition was 2.4%, and NSI high nutritional risk was 6.3%. The prevalence of MNA malnutrition was lowest among Robust-CN and highest among Frail-CI (0.5% in Robust-CN, 0.6% in Robust-CI, 2.8% in Pre-frail-CN, 7.3% in Pre-frail-CI, 15.4% in Frail-CN, and 23.1% in Frail-CI). Similarly, the prevalence of NSI high nutritional risk was lowest in Robust-CN (3.7%) and highest in Frail-CI (13.6%). Adjusted for sociodemographic and health status, pre-frailty/frailty-CI versus Robust-CN was associated with the highest odds ratio of association with MNA malnutrition (OR=8.16, p<0.001), although not the highest with NSI high nutritional risk (OR=1.48, p=0.017). CONCLUSIONS: An extraordinary high prevalence of malnutrition was observed among older adults with cognitive frailty who should be specially targeted for active intervention.

Sex modulates the association of fibroblast growth factor 21 with end-stage renal disease in Asian people with Type 2 diabetes: a 6.3-year prospective cohort study.

AIM: To study whether plasma fibroblast growth factor 21 independently predicts the risk of end-stage renal disease in Asian people with Type 2 diabetes. METHODS: In this prospective cohort study, 1700 Asian people with Type 2 diabetes were followed for a mean of 6.3 years in a regional hospital in Singapore. Incident end-stage renal disease was identified by linkage with a national renal registry. The association of baseline fibroblast growth factor 21 levels with risk of progression to end-stage renal disease was studied using survival analyses. RESULTS: Participants were aged 60 ± 10 years, with an average diabetes duration of 12 years. Their estimated GFR was 73 ± 28 ml/min/1.73 m2 and 62% had albuminuria at baseline. A total of 179 incident end-stage renal disease cases were identified. Plasma fibroblast growth factor 21 interacted with sex in its association with end-stage renal disease (Pinteraction = 0.003). A 1-sd increment in fibroblast growth factor 21 (natural log-transformed) was associated with a 1.32-fold (95% CI 1.05-1.66, P = 0.02) increased hazard for end-stage renal disease in women, after adjustment for traditional risk factors including estimated GFR and albuminuria. Taking death as a competing risk did not materially change the outcome [sub-distribution hazard ratio 1.35 (95% CI 1.11-1.66, P = 0.003)]. Fibroblast growth factor 21 did not predict end-stage renal disease risk in men after adjustment for baseline estimated GFR and albuminuria [hazard ratio 1.07 (95% CI 0.89-1.28, P = 0.49)]. CONCLUSIONS: Plasma fibroblast growth factor 21 level independently predicted risk of progression to end-stage renal disease in women with Type 2 diabetes. The pathophysiological relationships among FGF21, sex and renal progression warrant further study.

Association of nutrition and immune-endocrine dysfunction with muscle mass and performance in cognitively impaired older adults.

BACKGROUND: With lean mass declining early in Alzheimer's disease, muscle quality beyond quantity is relevant to physical performance. We sought to identify potentially modifiable factors for the differential loss of muscle mass (pre-sarcopenia) and its performance (sarcopenia) in older adults with mild cognitive impairment (MCI) and mild-to-moderate Alzheimer's disease (AD). METHODS: This is a cross-sectional study of 108 community-dwelling older adults with MCI and mild-to-moderate AD. Participants were categorized as: (i) No sarcopenia (normal muscle mass), (ii) Pre-sarcopenia (low muscle mass without weakness or slowness), (iii) Sarcopenia (low muscle mass AND weak grip strength and/or slow gait speed) using Asian cut-offs. Muscle quality was defined as the ratio of grip and knee extension strength to average arm and leg lean mass respectively. We measured cognitive, functional and physical (Short Physical Performance Battery, SPPB) performance; physical activity level; nutritional status; and blood biomarkers of inflammation and endocrine dysfunction. RESULTS: SPPB (p=0.033) and activity level (p=0.010) were highest in the pre-sarcopenic group. Pre-sarcopenic group had highest arm muscle quality [10.6 (7.7-12.2) vs 13.9 (12.6-15.7) vs 11.3 (9.7-12.8), p<0.001], despite significantly lower appendicular lean mass than non-sarcopenic group. In multi-nomial logistic regression reference to non-sarcopenic group, malnutrition independently increased risk for both pre-sarcopenia (Relative risk=7.53, 95% C.I 1.20-47.51, p=0.032) and sarcopenia (Relative risk=11.91, 95% C.I 2.85-49.77, p=0.001). A combined pro-inflammatory and endocrine deficient state significantly increased the risk of sarcopenia (Relative risk=5.17, 95% C.I 1.31-20.37, p=0.019). CONCLUSION: Malnutrition is a precursor for progressive loss of muscle mass, but a pro-inflammatory and endocrine deficient state may potentially aggravate decline in muscle quality to culminate in frank sarcopenia.

Attraction and consumption of methyl eugenol by male Bactrocera umbrosa Fabricius (Diptera: Tephritidae) promotes conspecific sexual communication and mating performance.

The Artocarpus fruit fly, Bactrocera umbrosa (Fabricius) (Diptera: Tephritidae), is an oligophagous fruit pest infesting Moraceae fruits, including jackfruit (Artocarpus heterophyllus Lamarck), a fruit commodity of high value in Malaysia. The scarcity of fundamental biological, physiological and ecological information on this pest, particularly in relation to behavioural response to phytochemical lures, which are instrumental to the success of many area-wide fruit fly control and management programmes, underpins the need for studies on this much-underrated pest. The positive response of B. umbrosa males to methyl eugenol (ME), a highly potent phytochemical lure, which attracts mainly males of many Bactrocera species, was shown to increase with increasing age. As early as 7 days after emergence (DAE), ca. 22% of males had responded to ME and over 50% by 10 DAE, despite no occurrence of matings (i.e. the males were still sexually immature). Male attraction to ME peaked from 10 to 27 DAE, which corresponded with the flies' attainment of sexual maturity. In wind-tunnel assays during the dusk courtship period, ME-fed males exhibited earlier calling activity and attracted a significantly higher percentage of virgin females compared with ME-deprived males. ME-fed males enjoyed a higher mating success than ME-deprived males at 1-day post ME feeding in semi-field assays. ME consumption also promotes aggregation behaviour in B. umbrosa males, as demonstrated in wind-tunnel and semi-field assays. We suggest that ME plays a prominent role in promoting sexual communication and enhancing mating performance of the Artocarpus fruit fly, a finding that is congruent with previous reports on the consequences of ME acquisition by other economically important Bactrocera species.

Characterizing Lyme Disease Surveillance in an Endemic State.

Lyme disease (LD) is the most common vector-borne disease in Maryland and the United States. Surveillance for LD is valuable for understanding the burden of the disease, particularly to assess whether the disease is spreading and to appreciate who is affected. However, not all cases of LD in Maryland are reported, and surveillance practices vary across each of Maryland's 24 local health departments (LHDs). To better understand this variability and to systematically characterize the surveillance process, we surveyed Maryland's LHDs regarding LD surveillance. The Maryland Local Health Department Lyme Disease Surveillance Survey has been administered annually since 2011. Questions asked each year included whether all LD reports are investigated or only a subset, and how many reports are not entered into the surveillance database. Since 2011, Maryland has lost surveillance personnel for LD. Each year from 2009 to 2012, a median 3598 (range 2462 to 5722) reports were not entered into the surveillance database and hence not investigated. These reports represent 43-55% of all reports received for the year. Over time, more LHDs chose to streamline their LD investigation approach by investigating only those reports that met the criteria for laboratory evidence of infection: in 2008, 5 (21%) LHDs investigated only a subset of LD reports; by 2013, this increased to 15 (63%). There is wide variability across LHDs in how LD investigations are conducted. Maryland LHDs have experienced a loss of LD surveillance personnel with a concomitant increase in the number of LHDs adopting a streamlined approach to investigating cases. These findings underscore the tremendous burden of LD on the public health agencies and highlight the need for alternative approaches that can both reduce burden and preserve surveillance data quality.

Cardiopulmonary resuscitation-from the patient's perspective.

With increasing emphasis on patient autonomy, patients are encouraged to be more involved in end-of-life issues, including the use of extraordinary efforts to prolong their lives. Being able to make anticipatory decisions is seen to promote autonomy, empower patients and optimise patient care. To facilitate shared decision-making, patients need to have a clear and accurate understanding of cardiopulmonary resuscitation (CPR). This study aims to understand the knowledge and perspectives of the local community regarding resuscitation options and end-of-life decision-making and to explore ways to improve the quality of end-of-life discussions. An interviewer-administered survey was conducted with a prospectively recruited group of surgical patients admitted postoperatively to the day surgery ward of a single tertiary institution in Singapore from April to May 2015. The survey, modelled after two validated questionnaires, measured patients' knowledge, attitudes and preferences regarding CPR in a series of 18 questions. Fifty-one out of 67 (76.1%) patients completed the survey. Results indicated that 80.4% (n=41) of participants correctly understood the purpose of CPR, but 64.7% (n=33) did not know of any possible complications of CPR. Less than half (n=21, 41.2%) of participants had thought about life support measures they wanted for themselves. Most of the participants agreed that they should personally be involved in making end-of-life decisions (n=44, 86.3%). Many patients had a poor knowledge of CPR and other resuscitation measures and the majority overestimated the success rate of CPR. However, a majority were receptive to improving their knowledge and keen to discuss end-of-life issues with physicians.

Improving Outcomes in Tendon Repair: A Critical Look at the Evidence for Flexor Tendon Repair and Rehabilitation.

LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Appreciate the variation and evolution of flexor tendon management 2. Know how to assess the patient who presents with a flexor tendon laceration. 3. Understand the biology of repairing flexor tendon lacerations. 4. Appreciate the technical challenges in flexor tendon repair relating to different zones. 5. Understand the rationale of postoperative hand therapy. 6. Have an overview of the types of secondary tendon surgery. BACKGROUND: Flexor tendon injury constitutes a considerable trauma workload for hand surgeons, and a vast amount of research is dedicated toward improving outcomes in tendon repair. This Continuing Medical Education article aims to provide an up-to-date evidence-based outline of flexor tendon surgery in the hand. METHODS: The authors reviewed the literature on flexor tendon repairs to include a balanced overview of the experimental and clinical research. For each section, the best levels of evidence were assessed in the context of past research to provide a comprehensive opinion on best management. RESULTS: The review highlights current trends in flexor tendon surgery, clinical assessment, anesthetic technique, surgical approach, repair technique, and rehabilitation. Carefully selected illustrations, figures, tables, and video have been used to supplement the findings of the review. CONCLUSIONS: Early active mobilization remains the only long-term proven strategy to improve outcomes. Incorporating intraoperative mobilization using "wide-awake" surgery could emerge to further improve tendon outcomes. Good surgical approach, meticulous surgery, up-to-date physiotherapy regimens, and patient education remain the cornerstone of obtaining best outcomes.