Pathways to new drug discovery in neuropsychiatry

There is currently a crisis in drug discovery for neuropsychiatric disorders, with a profound, yet unexpected drought in new drug development across the spectrum. In this commentary, the sources of this dilemma and potential avenues to redress the issue are explored. These include a critical review of diagnostic issues and of selection of participants for clinical trials, and the mechanisms for identifying new drugs and new drug targets. Historically, the vast majority of agents have been discovered serendipitously or have been modifications of existing agents. Serendipitous discoveries, based on astute clinical observation or data mining, remain a valid option, as is illustrated by the suggestion in the paper by Wahlqvist and colleagues that treatment with sulfonylurea and metformin reduces the risk of affective disorder. However, the identification of agents targeting disorder-related biomarkers is currently proving particularly fruitful. There is considerable hope for genetics as a purist, pathophysiologically valid pathway to drug discovery; however, it is unclear whether the science is ready to meet this promise. Fruitful paradigms will require a break from the orthodoxy, and creativity and risk may well be the fingerprints of success

Characterization of polyphenols in Australian sweet lupin (Lupinus angustifolius) seed coat by HPLC-DAD-ESI-MS/MS

Seeds of the legume lupin (Lupinus spp.) are becoming increasingly important as human food. The seed coat, at ~25% of the whole seed of Lupinus angustifolius (Australian sweet lupin, ASL), is the main by-product of lupin kernel flour production. The primary market for lupin seed coat is low value feed with very limited use in foods. In this study, seed coats of six ASL commercial varieties from two growing sites were sampled for identification and quantification of polyphenols using a high-performance liquid chromatography (HPLC) with diode array detector (DAD) and coupled with a triple quadrupole mass spectrometer which equipped with electrospray ionization source (ESI-MS/MS). Three flavones (apigenin-7-O-β-apiofuranosyl-6,8-di-C-β-glucopyranoside, vicenin 2, and apigenin-7-O-β-glucopyranoside), one isoflavone (genistein) and one dihydroflavonol derivative (aromadendrin-6-C-β-D-glucopyranosyl-7-O-[β-D-apiofuranosyl-(1 → 2)]-O-β-D-glucopyranoside), and several hydroxybenzoic and hydroxycinnamic acid derivatives were identified. Considerable variations in levels of individual polyphenols were found but apigenin-7-O-β-apiofuranosyl-6,8-di-C-β-glucopyranoside was the predominant polyphenol in all samples accounting for 73.08–82.89% of the total free polyphenols. These results suggest that ASL seed coat could be valuable dietary source of polyphenols. © 2018 Elsevier Lt

Three-dimensional food printing: Its readiness for a food and nutrition insecure world

Three-dimensional (3D) food printing is a rapidly emerging technology offering unprecedented potential for customised food design and personalised nutrition. Here, we evaluate the technological advances in extrusion-based 3D food printing and its possibilities to promote healthy and sustainable eating. We consider the challenges in implementing the technology in real-world applications. We propose viable applications for 3D food printing in health care, health promotion and food waste upcycling. Finally, we outline future work on 3D food printing in food safety, acceptability and economics, ethics and regulations. .

The students' voice: Strengths and weaknesses of an undergraduate medical curriculum in a developing country, a qualitative study

<p>Abstract</p> <p>Background</p> <p>In medical education, feedback from students' is essential in course evaluation and development. Students at Faculty of Medicine, University of Colombo, Sri Lanka complete a five year medical curriculum comprising of five different streams. We aimed to evaluate the five year medical curriculum at the Faculty of Medicine, University of Colombo, Sri Lanka.</p> <p>Methods</p> <p>A qualitative research was conducted among recent graduates of the faculty. Students' opinions on strengths and weaknesses of the curriculum were collected via questionnaires, which were analysed and classified into common themes. A focus group discussion (FGD) based on these themes was conducted among two student groups, each comprising of a facilitator, two observers and nine students selected as a representative sample from questionnaire respondents. FGDs were conducted using a semi-structured set of open-ended questions to guide participants and maintain consistency between groups. The FGD evaluated the reasons behind students' perceptions, attitudes, emotions and perceived solution. Verbal and non-verbal responses were transcribed and analysed.</p> <p>Results</p> <p>Questionnaire response rate was 82% (153/186). Students highlighted 68 and 135 different responses on strengths and weaknesses respectively. After analysis of both questionnaire and FGD results the following themes emerged: a well organized module system, increased frequency of assessments, a good variety in clinical appointments, lack of specific objectives and assessments at clinical appointments, community and behavioural sciences streams beneficial but too much time allocation, lengthy duration of course, inadequate knowledge provided on pharmacology and pathology.</p> <p>Conclusion</p> <p>We demonstrate how a brief qualitative method could be efficiently used to evaluate a curriculum spanning a considerable length of time. This method provided an insight into the students' attitudes and perceptions of the present faculty curriculum. Qualitative feedback from students highlighted certain key areas that need attention and also possible solutions as perceived by the students'.</p

Nutrition, sarcopenia and frailty: an Asian perspective

Despite a growing body of evidence that nutrition plays a key role in the pathophysiology, prevention and intervention programs of frailty and sarcopenia, as well as in promoting brain health, the awareness and the need to study the relationship between nutrition and functional goals of healthy ageing have not received as much attention or support from research or policy makers. This review reports on the state of knowledge relating to availability of nutrition survey data for older people relating to prevalence of frailty and sarcopenia in Asia, using data from Netherlands for comparison. Data were obtained from a meeting of a group of nutrition experts from Asia supplemented by literature search using key terms of nutrition, frailty, and sarcopenia. Although nutrition surveys may be carried out regularly in several countries, surveys are mainly carried out for the general adult population rather than specifically among the elderly population, and little data is available relating to the impact of nutrition on sarcopenia and frailty. There is an urgent need for more nutritional data relating to maintaining function with age as opposed to disease prevention, to guide health promotion policies and clinical management of increasingly older population and patients. A shift in the gathering of national nutrition data may need to include such functional measurements in relation to older people, as the latter forms the rapidly growing sector of ageing populations world-wide

Is impaired energy regulation the core of the metabolic syndrome in various ethnic groups of the USA and Taiwan?

<p>Abstract</p> <p>Background</p> <p>The metabolic syndrome (MetS) concept is widely used in public health and clinical settings without an agreed pathophysiology. We have re-examined the MetS in terms of body fuels, so as to provide a coherent cross-cultural pathogenesis.</p> <p>Methods</p> <p>National Health and Nutrition Examination Survey (NHANES 2001-2) with n = 2254 and Taiwanese National Health Interview Survey (NHIS) sub-set for hypertension, hyperglycemia and hyperlipidemia assessment (TwSHHH 2002), n = 5786, were used to compare different ethnicities according to NCEP-ATPIII (NCEP-tw) criteria for METS. Exploratory factor analysis (EFA) using principal components (PC) was employed to differentiate and unify MetS components across four ethnicities, gender, age-strata, and urban-rural settings.</p> <p>Results</p> <p>The first two factors from the PC analysis (PCA) accounted for from 55.2% (non-Hispanic white) to 63.7% (Taiwanese) of the variance. Rotated factor loadings showed that the six MetS components provided three clusters: the impaired energy regulation (IER) components (waist circumference, WC, fasting triglycerides, TG, and fasting plasma glucose, FPG), systolic and diastolic blood pressures (BPs), and HDL-cholesterol, where the IER components accounted for 25-26% of total variance of MetS components. For the three US ethnic subgroups, factor 1 was mainly determined by IER and HDL-cholesterol, and factor 2 was related to the BP components. For Taiwanese, IER was determinant for both factors, and BPs and HDL-cholesterol were related to factors 1 and 2 respectively.</p> <p>Conclusions</p> <p>There is a MetS core which unifies populations. It comprises WC, TG and FPG as a core, IER, which may be expressed and modulated in various second order ways.</p

Computation tools for the combat of cardiovascular heart disease

The paper discusses two potential applications of computational technologies to combat cardiovascular heart disease in Singapore. The first application involves the exploitation of neural networks for the risk prediction of coronary heart disease. The second application involves the potential integration of artificial intelligence and high performance modelling with clinical biology for the analysis and visualisation of atherosclerosis related structure. The implementation of these computation tools in phases constitutes initial efforts in the development of a digital clinical atherosclerosis laboratory to assist in the prevention and treatment of cardiovascular heart disease

The simulation of wildland-urban interface fire evacuation: The WUI-NITY platform

Wildfires are a significant safety risk to populations adjacent to wildland areas, known as the wildland-urban interface (WUI). This paper introduces a modelling platform called WUI-NITY. The platform is built on the Unity3D game engine and simulates and visualises human behaviour and wildfire spread during an evacuation of WUI communities. The purpose of this platform is to enhance the situational awareness of responders and residents during evacuation scenarios by providing information on the dynamic evolution of the emergency. WUI-NITY represents current and predicted conditions by coupling the three key modelling layers of wildfire evacuation, namely the fire, pedestrian, and traffic movement. This allows predictions of evacuation behaviour over time. The current version of WUI-NITY demonstrates the feasibility and advantages of coupling the modelling layers. Its wildfire modelling layer is based on FARSITE, the pedestrian layer implements a dedicated pedestrian response and movement model, and the traffic layer includes a traffic evacuation model based on the Lighthill-Whitham-Richards model. The platform also includes a sub-model called PERIL that designs the spatial location of trigger buffers. The main contribution of this work is in the development of a modular and model-agnostic (i.e., not linked to a specific model) platform with consistent levels of granularity (allowing a comparable modelling resolution in the representation of each layer) in all three modelling layers. WUI-NITY is a powerful tool to protect against wildfires; it can enable education and training of communities, forensic studies of past evacuations and dynamic vulnerability assessment of ongoing emergencies

Age- and gender-specific population attributable risks of metabolic disorders on all-cause and cardiovascular mortality in Taiwan

[[abstract]]ABSTRACT: BACKGROUND: The extent of attributable risks of metabolic syndrome (MetS) and its components on mortality remains unclear, especially with respect to age and gender. We aimed to assess the age- and gender-specific population attributable risks (PARs) for cardiovascular disease (CVD)-related mortality and all-cause mortality for public health planning. METHODS: A total of 2,092 men and 2,197 women 30 years of age and older, who were included in the 2002 Taiwan Survey of Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH), were linked to national death certificates acquired through December 31, 2009. Cox proportional hazard models were used to calculate adjusted hazard ratios and PARs for mortality, with a median follow-up of 7.7 years. RESULTS: The respective PAR percentages of MetS for all-cause and CVD-related mortality were 11.6 and 39.2 in men, respectively, and 18.6 and 44.4 in women, respectively. Central obesity had the highest PAR for CVD mortality in women (57.5%), whereas arterial hypertension had the highest PAR in men (57.5%). For all-cause mortality, younger men and post-menopausal women had higher PARs related to Mets and its components; for CVD mortality, post-menopausal women had higher overall PARs than their pre-menopausal counterparts. CONCLUSIONS: MetS has a limited application to the PAR for all-cause mortality, especially in men; its PAR for CVD mortality is more evident. For CVD mortality, MetS components have higher PARs than MetS itself, especially hypertension in men and waist circumference in post-menopausal women. In addition, PARs for diabetes mellitus and low HDL-cholesterol may exceed 20%. We suggest differential control of risk factors in different subpopulation as a strategy to prevent CVD-related mortality

Assessing validity of a short food frequency questionnaire on present dietary intake of elderly Icelanders

<p>Abstract</p> <p>Background</p> <p>Few studies exist on the validity of food frequency questionnaires (FFQs) administered to elderly people. The aim of this study was to assess the validity of a short FFQ on present dietary intake, developed specially for the AGES-Reykjavik Study, which includes 5,764 elderly individuals. Assessing the validity of FFQs is essential before they are used in studies on diet-related disease risk and health outcomes.</p> <p>Method</p> <p>128 healthy elderly participants (74 y ± 5.7; 58.6% female) answered the AGES-FFQ, and subsequently filled out a 3-day weighed food record. Validity of the AGES-FFQ was assessed by comparing its answers to the dietary data obtained from the weighed food records, using Spearman's rank correlation, Chi-Square/Kendall's tau, and a Jonckheere-Terpstra test for trend.</p> <p>Result</p> <p>For men a correlation ≥ 0.4 was found for potatoes, fresh fruits, oatmeal/muesli, cakes/cookies, candy, dairy products, milk, pure fruit juice, cod liver oil, coffee, tea and sugar in coffee/tea (r = 0.40-0.71). A lower, but acceptable, correlation was also found for raw vegetables (r = 0.33). The highest correlation for women was found for consumption of rye bread, oatmeal/muesli, raw vegetables, candy, dairy products, milk, pure fruit juice, cod liver oil, coffee and tea (r = 0.40-0.61). An acceptable correlation was also found for fish topping/salad, fresh fruit, blood/liver sausage, whole-wheat bread, and sugar in coffee/tea (r = 0.28-0.37). Questions on meat/fish meals, cooked vegetables and soft drinks did not show a significant correlation to the reference method. Pearson Chi-Square and Kendall's tau showed similar results, as did the Jonckheere-Terpstra trend test.</p> <p>Conclusion</p> <p>A majority of the questions in the AGES-FFQ had an acceptable correlation and may be used to rank individuals according to their level of intake of several important foods/food groups. The AGES-FFQ on present diet may therefore be used to study the relationship between consumption of several specific foods/food groups and various health-related endpoints gathered in the AGES-Reykjavik Study.</p