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Publication Consistency of eating rate, oral processing behaviours and energy intake across meals(2017) McCrickerd, K; Forde, C.G; PHYSIOLOGYFaster eating has been identified as a risk factor for obesity and the current study tested whether eating rate is consistent within an individual and linked to energy intake across multiple meals. Measures of ad libitum intake, eating rate, and oral processing at the same or similar test meal were recorded on four non-consecutive days for 146 participants (117 male, 29 female) recruited across four separate studies. All the meals were video recorded, and oral processing behaviours were derived through behavioural coding. Eating behaviours showed good to excellent consistency across the meals (intra-class correlation coefficients > 0.76, p < 0.001) and participants who ate faster took larger bites (? ? 0.39, p < 0.001) and consistently consumed more energy, independent of meal palatability, sex, body composition and reported appetite (? ? 0.17, p ? 0.025). Importantly, eating faster at one meal predicted faster eating and increased energy intake at subsequent meals (? > 0.20, p < 0.05). Faster eating is relatively consistent within individuals and is predictive of faster eating and increased energy intake at subsequent similar meals consumed in a laboratory context, independent of individual differences in body composition. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.Publication A mixed flavonoid-fish oil supplement induces immune-enhancing and anti-inflammatory transcriptomic changes in adult obese and overweight women—A randomized controlled trial(2016) Cialdella-Kam, L; Nieman, D.C; Knab, A.M; Shanely, R.A; Meaney, M.P; Jin, F; Sha, W; Ghosh, S; DUKE-NUS MEDICAL SCHOOLFlavonoids and fish oils have anti-inflammatory and immune-modulating influences. The purpose of this study was to determine if a mixed flavonoid-fish oil supplement (Q-Mix; 1000 mg quercetin, 400 mg isoquercetin, 120 mg epigallocatechin (EGCG) from green tea extract, 400 mg n3-PUFAs (omega-3 polyunsaturated fatty acid) (220 mg eicosapentaenoic acid (EPA) and 180 mg docosahexaenoic acid (DHA)) from fish oil, 1000 mg vitamin C, 40 mg niacinamide, and 800 µg folic acid) would reduce complications associated with obesity; that is, reduce inflammatory and oxidative stress markers and alter genomic profiles in overweight women. Overweight and obese women (n = 48; age = 40–70 years) were assigned to Q-Mix or placebo groups using randomized double-blinded placebo-controlled procedures. Overnight fasted blood samples were collected at 0 and 10 weeks and analyzed for cytokines, C-reactive protein (CRP), F2-isoprostanes, and whole-blood-derived mRNA, which was assessed using Affymetrix HuGene-1_1 ST arrays. Statistical analysis included two-way ANOVA models for blood analytes and gene expression and pathway and network enrichment methods for gene expression. Plasma levels increased with Q-Mix supplementation by 388% for quercetin, 95% for EPA, 18% for DHA, and 20% for docosapentaenoic acid (DPA). Q-Mix did not alter plasma levels for CRP (p = 0.268), F2-isoprostanes (p = 0.273), and cytokines (p > 0.05). Gene set enrichment analysis revealed upregulation of pathways in Q-Mix vs. placebo related to interferon-induced antiviral mechanism (false discovery rate, FDR < 0.001). Overrepresentation analysis further disclosed an inhibition of phagocytosis-related inflammatory pathways in Q-Mix vs. placebo. Thus, a 10-week Q-Mix supplementation elicited a significant rise in plasma quercetin, EPA, DHA, and DPA, as well as stimulated an antiviral and inflammation whole-blood transcriptomic response in overweight women. © 2016 by the authors; licensee MDPI, Basel, Switzerland.Publication Comparative proteomics reveals human pluripotent stem cell-derived limbal epithelial stem cells are similar to native ocular surface epithelial cells(2015) Mikhailova, A; Jylhä, A; Rieck, J; Nättinen, J; Ilmarinen, T; Veréb, Z; Aapola, U; Beuerman, R; Petrovski, G; Uusitalo, H; Skottman, H; DUKE-NUS MEDICAL SCHOOLLimbal epithelial stem cells (LESCs) are tissue-specific stem cells responsible for renewing the corneal epithelium. Acute trauma or chronic disease affecting LESCs may disrupt corneal epithelial renewal, causing vision threatening and painful ocular surface disorders, collectively referred to as LESC deficiency (LESCD). These disorders cannot be treated with traditional corneal transplantation and therefore alternative cell sources for successful cell-based therapy are needed. LESCs derived from human pluripotent stem cells (hPSCs) are a prospective source for ocular surface reconstruction, yet critical evaluation of these cells is crucial before considering clinical applications. In order to quantitatively evaluate hPSC-derived LESCs, we compared protein expression in native human corneal cells to that in hPSC-derived LESCs using isobaric tag for relative and absolute quantitation (iTRAQ) technology. We identified 860 unique proteins present in all samples, including proteins involved in cell cycling, proliferation, differentiation and apoptosis, various LESC niche components, and limbal and corneal epithelial markers. Protein expression profiles were nearly identical in LESCs derived from two different hPSC lines, indicating that the differentiation protocol is reproducible, yielding homogeneous cell populations. Their protein expression profile suggests that hPSC-derived LESCs are similar to the human ocular surface epithelial cells, and possess LESC-like characteristics.Publication Genetic diversity in new members of the reticulocyte binding protein family in Thai Plasmodium vivax isolates(Public Library of Science, 2012) Kosaisavee V.; Lek-Uthai U.; Suwanarusk R.; Grüner A.C.; Russell B.; Nosten F.; Rénia L.; Snounou G.; MICROBIOLOGY AND IMMUNOLOGYBackground: Plasmodium vivax merozoites specifically invade reticulocytes. Until recently, two reticulocyte-binding proteins (Pvrbp1 and Pvrbp2) expressed at the apical pole of the P. vivax merozoite were considered to be involved in reticulocyte recognition. The genome sequence recently obtained for the Salvador I (Sal-I) strain of P. vivax revealed additional genes in this family, and in particular Pvrbp2a, Pvrbp2b (Pvrbp2 has been renamed as Pvrbp2c) and two pseudogenes Pvrbp2d and Pvrbp3. It had been previously found that Pvrbp2c is substantially more polymorphic than Pvrbp1. The primary goal of this study was to ascertain the level of polymorphism of these new genes. Methodology/Principal Findings: The sequence of the Pvrbp2a, Pvrbp2b, Pvrbp2d and Pvrbp3 genes were obtained by amplification/cloning using DNA purified from four isolates collected from patients that acquired the infection in the four cardinal regions of Thailand (west, north, south and east). An additional seven isolates from western Thailand were analyzed for gene copy number variation. There were significant polymorphisms exhibited by these genes (compared to the reference Sal-I strain) with the ratio of mutations leading to a non-synonymous or synonymous amino acid change close to 3:1 for Pvrbp2a and Pvrbp2b. Although the degree of polymorphism exhibited by these two genes was higher than that of Pvrbp1, it did not reach the exceptional diversity noted for Pvrbp2c. It was interesting to note that variations in the copy number of Pvrbp2a and Pvrbp2b occurred in some isolates. Conclusions/Significance: The evolution of different members of the Pvrbp2 family and their relatively high degree of polymorphism suggests that the proteins encoded by these genes are important for parasite survival and are under immune selection. Our data also shows that there are highly conserved regions in rbp2a and rbp2b, which might provide suitable targets for future vaccine development against the blood stage of P. vivax. © 2012 Kosaisavee et al.Publication Age at natural menopause and risk of type 2 diabetes: a prospective cohort study(Springer Verlag, 2017) Muka, T; Asllanaj, E; Avazverdi, N; Jaspers, L; Stringa, N; Milic, J; Ligthart, S; Ikram, M.A; Laven, J.S.E; Kavousi, M; Dehghan, A; Franco, O.H; DUKE-NUS MEDICAL SCHOOLAims/hypothesis: In this study, we aimed to examine the association between age at natural menopause and risk of type 2 diabetes, and to assess whether this association is independent of potential mediators. Methods: We included 3639 postmenopausal women from the prospective, population-based Rotterdam Study. Age at natural menopause was self-reported retrospectively and was treated as a continuous variable and in categories (premature, <40 years; early, 40–44 years; normal, 45–55 years; and late menopause, >55 years [reference]). Type 2 diabetes events were diagnosed on the basis of medical records and glucose measurements from Rotterdam Study visits. HRs and 95% CIs were calculated using Cox proportional hazards models, adjusted for confounding factors; in another model, they were additionally adjusted for potential mediators, including obesity, C-reactive protein, glucose and insulin, as well as for levels of total oestradiol and androgens. Results: During a median follow-up of 9.2 years, we identified 348 individuals with incident type 2 diabetes. After adjustment for confounders, HRs for type 2 diabetes were 3.7 (95% CI 1.8, 7.5), 2.4 (95% CI 1.3, 4.3) and 1.60 (95% CI 1.0, 2.8) for women with premature, early and normal menopause, respectively, relative to those with late menopause (ptrend <0.001). The HR for type 2 diabetes per 1 year older at menopause was 0.96 (95% CI 0.94, 0.98). Further adjustment for BMI, glycaemic traits, metabolic risk factors, C-reactive protein, endogenous sex hormone levels or shared genetic factors did not affect this association. Conclusions/interpretation: Early onset of natural menopause is an independent marker for type 2 diabetes in postmenopausal women. © 2017, The Author(s).Publication Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations(BioScientifica Ltd., 2016) Christiansen, J.S; Backeljauw, P.F; Bidlingmaier, M; MEDICINEObjective: The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants: A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence: Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process: Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions: LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations. © 2016 European Society of Endocrinology.Publication Recovery of methamphetamine associated cardiomyopathy predicted by late gadolinium enhanced cardiovascular magnetic resonance(2009) Lopez, J.E; Yeo, K; Caputo, G; Buonocore, M; Schaefer, S; DUKE-NUS MEDICAL SCHOOLMethamphetamine is known to cause a cardiomyopathy which may be reversible with appropriate medical therapy and cessation of use. Late gadolinium enhancement cardiovascular magnetic resonance (CMR) has been shown to identify fibrosis in ischemic and non-ischemic cardiomyopathies. We present a case of severe methamphetamine-associated cardiomyopathy in which cardiac function recovered after 6 months. Evaluation by CMR using late gadolinium enhancement was notable for an absence of enhancement, suggesting an absence of irreversible myocyte injury and a good prognosis. CMR may be useful to predict recovery in toxin-associated non-ischemic cardiomyopathies. © 2009 Lopez et al; licensee BioMed Central Ltd.Publication Monochromatic pupillometry in unilateral glaucoma discloses no adaptive changes subserved by the ipRGCs(2014) Nissen, C; Sander, B; Milea, D; Kolko, M; Herbst, K; Hamard, P; Lund-Andersen, H; DUKE-NUS MEDICAL SCHOOLPurpose: To detect signs of a possible adaptive mechanism of the intrinsically photosensitive ganglion cells in unilateral glaucoma. Method: Eleven patients with unilateral glaucoma, classified by automated perimetry (glaucoma: mean deviation < 0), were studied by monochromatic pupillometry, employing red (660 nm) or blue (470 nm) light, and by optical coherence tomography of the peripapillary retinal nerve fiber layer. The main outcome measure in pupillometry, the area under the curve (AUC), i.e., the product of pupillary contraction amplitude and time, was determined during and after light exposure in glaucomatous and unafflicted fellow eyes and compared to the AUCs of a healthy, age-matched control group. Results: The AUC to stimulation with blue light was significantly reduced in glaucomatous eyes, both during and after stimulus, compared with that of fellow, unafflicted eyes (p ≤ 0.014). The AUC to red light stimulation was reduced during (p = 0.035), but not after (p ≥ 0.072), exposure in glaucomatous eyes. In the unafflicted fellow eyes, the pupillary response to blue light did not differ from that of healthy controls. Conclusion: The pupillary response to blue light was decreased in the glaucomatous eyes of unilateral glaucoma. No difference was detected between the pupillary light response of the unafflicted fellow eyes and that of a healthy, age-matched control group. Thus no sign of an adaptive mechanism was detected, neither in the glaucomatous nor in the unafflicted fellow eyes, and consequently glaucoma appears to differ from non-arteritic anterior ischemic optic neuropathy. © 2014 Nissen, Sander, Milea, Kolko, Herbst, Hamard and Lund-Andersen.Publication The human cortex possesses a reconfigurable dynamic network architecture that is disrupted in psychosis(Nature Publishing Group, 2018) Reinen, J.M; Chén, O.Y; Hutchison, R.M; Yeo, B.T.T; Anderson, K.M; Sabuncu, M.R; Öngür, D; Roffman, J.L; Smoller, J.W; Baker, J.T; Holmes, A.J; ELECTRICAL AND COMPUTER ENGINEERINGHigher-order cognition emerges through the flexible interactions of large-scale brain networks, an aspect of temporal coordination that may be impaired in psychosis. Here, we map the dynamic functional architecture of the cerebral cortex in healthy young adults, leveraging this atlas of transient network configurations (states), to identify state- and network-specific disruptions in patients with schizophrenia and psychotic bipolar disorder. We demonstrate that dynamic connectivity profiles are reliable within participants, and can act as a fingerprint, identifying specific individuals within a larger group. Patients with psychotic illness exhibit intermittent disruptions within cortical networks previously associated with the disease, and the individual connectivity profiles within specific brain states predict the presence of active psychotic symptoms. Taken together, these results provide evidence for a reconfigurable dynamic architecture in the general population and suggest that prior reports of network disruptions in psychosis may reflect symptom-relevant transient abnormalities, rather than a time-invariant global deficit. © 2018 The Author(s).Publication Geographic variation in dengue seroprevalence and force of infection in the urban paediatric population of Indonesia(2018) Tam C.C.; O?Driscoll M.; Taurel A.-F.; Nealon J.; Hadinegoro S.R.; DEAN'S OFFICE (SSH SCH OF PUBLIC HEALTH); SAW SWEE HOCK SCHOOL OF PUBLIC HEALTHUnderstanding the heterogeneous nature of dengue transmission is important for prioritizing and guiding the implementation of prevention strategies. However, passive surveillance data in endemic countries are rarely adequately informative. We analyzed data from a cluster-sample, cross-sectional seroprevalence study in 1?18 year-olds to investigate geographic differences in dengue seroprevalence and force of infection in Indonesia. We used catalytic models to estimate the force of infection in each of the 30 randomly selected sub-districts. Based on these estimates, we determined the proportion of sub-districts expected to reach seroprevalence levels of 50%, 70% and 90% by year of age. We used population averaged generalized estimating equation models to investigate individual- and cluster-level determinants of dengue seropositivity. Dengue force of infection varied substantially across Indonesia, ranging from 4.3% to 30.0% between sub-districts. By age nine, 60% of sub-districts are expected to have a seroprevalence �70%, rising to 83% by age 11. Higher odds of seropositivity were associated with higher population density (OR = 1.54 per 10-fold rise in population density, 95% CI: 1.03?2.32) and with City (relative to Regency) administrative status (OR = 1.92, 95% CI: 1.32?2.79). Our findings highlight the substantial variation in dengue endemicity within Indonesia and the importance of understanding spatial heterogeneity in dengue transmission intensity for optimal dengue prevention strategies including future implementation of dengue vaccination programmes. ? 2018 Tam et al. http://creativecommons.org/licenses/by/4.0/.