Detection of Fall Risk in Multiple Sclerosis by Gait Analysis-An Innovative Approach Using Feature Selection Ensemble and Machine Learning Algorithms.

One of the common causes of falls in people with Multiple Sclerosis (pwMS) is walking impairment. Therefore, assessment of gait is of importance in MS. Gait analysis and fall detection can take place in the clinical context using a wide variety of available methods. However, combining these methods while using machine learning algorithms for detecting falls has not been performed. Our objective was to determine the most relevant method for determining fall risk by analyzing eleven different gait data sets with machine learning algorithms. In addition, we examined the most important features of fall detection. A new feature selection ensemble (FS-Ensemble) and four classification models (Gaussian Naive Bayes, Decision Tree, k-Nearest Neighbor, Support Vector Machine) were used. The FS-Ensemble consisted of four filter methods: Chi-square test, information gain, Minimum Redundancy Maximum Relevance and RelieF. Various thresholds (50%, 25% and 10%) and combination methods (Union, Union 2, Union 3 and Intersection) were examined. Patient-reported outcomes using specialized walking questionnaires such as the 12-item Multiple Sclerosis Walking Scale (MSWS-12) and the Early Mobility Impairment Questionnaire (EMIQ) achieved the best performances with an F1 score of 0.54 for detecting falls. A combination of selected features of MSWS-12 and EMIQ, including the estimation of walking, running and stair climbing ability, the subjective effort as well as necessary concentration and walking fluency during walking, the frequency of stumbling and the indication of avoidance of social activity achieved the best recall of 75%. The Gaussian Naive Bayes was the best classification model for detecting falls with almost all data sets. FS-Ensemble improved the classification models and is an appropriate technique for reducing data sets with a large number of features. Future research on other risk factors, such as fear of falling, could provide further insights.

Carnauba wax utilization in salt encapsulation: application in bread.

The present work aims to develop encapsulated NaCl in carnauba wax for bread application, to reduce the salt utilization and assess its impacts on the rheological dough parameters and saltiness perception. Encapsulated salt was obtained blending salt crystals and molten Carnauba wax. Four different bread formulations were produced: 2.0% non-encapsulated salt; 2.0% Encapsulated Salt; 1.5% Encapsulated Salt; 1.0% Encapsulated Salt. Farinograph and alveograph analyses were performed to assess the dough rheology parameters and sensory analysis was conducted to evaluate saltiness. Encapsulation was effective to control Na+ ions release. They vary from 17 to 32 ppm the dissolution of sodium ions in the non-encapsulated and encapsulated samples, respectively. The alveograph and farinograph analyses showed that the 1.5E bread formulation was the closest to the control sample in rheological properties. Finally, a sensory analysis showed no difference in the saltiness perception between control and 1.5% encapsulated salt (4.65 and 4.69 respectively), indicating that carnauba wax encapsulated salt effectively reduced until 35% of salt the bread without changing the saltiness.

Muscle fiber type-specific autophagy responses following an overnight fast and mixed meal ingestion in human skeletal muscle.

The aim of the present study was to investigate the fiber type-specific abundance of autophagy-related proteins after an overnight fast and following ingestion of a mixed meal in human skeletal muscle. Twelve overweight, healthy young male volunteers underwent a 3-h mixed meal tolerance test following an overnight fast. Blood samples were collected in the overnight-fasted state and throughout the 180-min postmeal period. Skeletal muscle biopsies were collected in the fasted state, and at 30 and 90 min after meal ingestion. Protein content of key autophagy markers and upstream signaling responses were measured in whole muscle and pooled single fibers using immunoblotting. In the fasted state, type I fibers displayed lower LC3B-I but higher LC3B-II abundance and higher LC3B-II/LC3B-I ratio compared with type II fibers (P < 0.05). However, there were no fiber type differences in p62/SQSTM1, unc-51 like autophagy activating kinase (ULK1), ATG5, or ATG12 (P > 0.05). Compared with the fasted state, there was a reduction in LC3B-II abundance, indicative of lower autophagosome content, in whole muscle and in both type I and type II fibers following meal ingestion (P < 0.05). This reduction in autophagosome content occurred alongside similar increases in p-AktS473 and p-mTORS2448 in both type I and type II muscle fibers (P < 0.05). In human skeletal muscle, type I fibers have a greater autophagosome content than type II fibers in the overnight-fasted state despite comparable abundance of other key upstream autophagy proteins. Autophagy is rapidly inhibited in both fiber types following the ingestion of a mixed meal.NEW & NOTEWORTHY This study examined the fiber type-specific content of key autophagy proteins in human muscle. We showed that markers of autophagosome content are higher in type I fibers in the overnight-fasted state, whereas autophagy is rapidly inhibited in both type I and type II fibers after the ingestion of a mixed meal.

Studies on nutritional and functional properties of various genotypes of Andean beans.

Andean bean group have a wide number of genotypes and are available as a source of nutrients and antioxidant compounds in a diet. Proteins, minerals, phenolic compounds, phytic acid, and antioxidant activity were evaluated in 14 white, red, and mottled seed coat genotypes. The Ca, Mg and Cu contents presented the greatest variability. The white seed coat genotypes presented lower phenolic compounds and antioxidant activity levels than the red and mottled seed coat genotypes. A strong correlation between phenolic compounds and antioxidant activity was observed, and hierarchical cluster analysis showed the formation of three groups (G1, G2 and G3). G1 and G2 can be recommended to individuals who want foods with a high content of antioxidant compounds, while any group can be consumed to meet the demand for a diet rich in minerals. G1 and G3 can be recommended to individuals who want a diet high in protein. Changes in eating habits are a barrier to incorporating new sources of nutrients into a traditional diet. However, Andean beans can easily be incorporated into the diets of those who already consume beans daily, as Andean beans can be prepared in the same manner as other beans. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05157-7.

Digital Biomarkers in Multiple Sclerosis.

For incurable diseases, such as multiple sclerosis (MS), the prevention of progression and the preservation of quality of life play a crucial role over the entire therapy period. In MS, patients tend to become ill at a younger age and are so variable in terms of their disease course that there is no standard therapy. Therefore, it is necessary to enable a therapy that is as personalized as possible and to respond promptly to any changes, whether with noticeable symptoms or symptomless. Here, measurable parameters of biological processes can be used, which provide good information with regard to prognostic and diagnostic aspects, disease activity and response to therapy, so-called biomarkers Increasing digitalization and the availability of easy-to-use devices and technology also enable healthcare professionals to use a new class of digital biomarkers-digital health technologies-to explain, influence and/or predict health-related outcomes. The technology and devices from which these digital biomarkers stem are quite broad, and range from wearables that collect patients' activity during digitalized functional tests (e.g., the Multiple Sclerosis Performance Test, dual-tasking performance and speech) to digitalized diagnostic procedures (e.g., optical coherence tomography) and software-supported magnetic resonance imaging evaluation. These technologies offer a timesaving way to collect valuable data on a regular basis over a long period of time, not only once or twice a year during patients' routine visit at the clinic. Therefore, they lead to real-life data acquisition, closer patient monitoring and thus a patient dataset useful for precision medicine. Despite the great benefit of such increasing digitalization, for now, the path to implementing digital biomarkers is widely unknown or inconsistent. Challenges around validation, infrastructure, evidence generation, consistent data collection and analysis still persist. In this narrative review, we explore existing and future opportunities to capture clinical digital biomarkers in the care of people with MS, which may lead to a digital twin of the patient. To do this, we searched published papers for existing opportunities to capture clinical digital biomarkers for different functional systems in the context of MS, and also gathered perspectives on digital biomarkers under development or already existing as a research approach.

Profiles of eHealth Adoption in Persons with Multiple Sclerosis and Their Caregivers.

(1) Background: Persons with multiple sclerosis (pwMS) are often characterized as ideal adopters of new digital healthcare trends, but it is worth thinking about whether and which pwMS will be targeted and served by a particular eHealth service like a patient portal. With our study, we wanted to explore needs and barriers for subgroups of pwMS and their caregivers when interacting with eHealth services in care and daily living. (2) Methods: This study comprises results from two surveys: one collecting data from pwMS and their relatives (as informal caregivers) and another one providing information on the opinions and attitudes of healthcare professionals (HCPs). Data were analyzed descriptively and via generalized linear models. (3) Results: 185 pwMS, 25 informal caregivers, and 24 HCPs in the field of MS participated. Nine out of ten pwMS used information technology on a daily base. Individual impairments like in vision and cognition resulted in individual needs like the desire to actively monitor their disease course or communicate with their physician in person. HCPs reported that a complete medication overview, additional medication information, overview of future visits and a reminder of medication intake would be very helpful eHealth features for pwMS, while they themselves preferred features organizing and enriching future visits. (4) Conclusions: A closer look at the various profiles of eHealth adoption in pwMS and their caregivers indicated that there is a broad and robust enthusiasm across several subgroups that does not exclude anyone in general, but constitutes specific areas of interest. For pwMS, the focus was on eHealth services that connect previously collected information and make them easily accessible and understandable.

Improving Digital Patient Care: Lessons Learned from Patient-Reported and Expert-Reported Experience Measures for the Clinical Practice of Multidimensional Walking Assessment.

BACKGROUND: Walking assessment (WA) enables meaningful patient mobility assessment. In this context, patient satisfaction with WA can influence assessment compliance and indirectly affect outcomes. One opportunity to assess patient satisfaction is patient-reported and expert-reported experience measures (PREM). Research on PREMs and WA in daily clinical multiple sclerosis (MS) practice does not exist yet. METHODS: We surveyed people with MS about their experience and assessed healthcare professionals' experience via an interview after patients completed WA. RESULTS: Gait parameters were related to perceived difficulty and strain during performance. Less impaired patients perceived the WA to be less difficult and exhausting but were less likely to use WA results for themselves. Men and patients with higher impairment would perform WA more frequently. A good workflow, a fully performed WA with standardized testing, fully functional measurement systems, support and safeguarding by staff in case of falls, direct feedback after the testing, and patients' motivation are identified by the experts as necessary factors for a successful WA. CONCLUSIONS: As patients' experience has an impact on patients' outcomes, long-term monitoring of PREMs should become an integral part of the healthcare service to identify and avoid problems early.

Nanofocusing with aberration-corrected rotationally parabolic refractive X-ray lenses. Corrigendum.

A correction in the paper by Seiboth et al. [(2018). J. Synchrotron Rad. 25, 108-115] is made.

Electronic Health Interventions in the Case of Multiple Sclerosis: From Theory to Practice.

(1) Background: eHealth interventions play a growing role in shaping the future healthcare system. The integration of eHealth interventions can enhance the efficiency and quality of patient management and optimize the course of treatment for chronically ill patients. In this integrative review, we discuss different types of interventions, standards and advantages of quality eHealth approaches especially for people with multiple sclerosis (pwMS). (2) Methods: The electronic databases PubMed, Cochrane and Web of Science were searched to identify potential articles for eHealth interventions in pwMS; based on 62 articles, we consider different ways of implementing health information technology with various designs. (3) Results: There already exist some eHealth interventions for single users with a single-use case, interventions with a social setting, as well as eHealth interventions that integrate various single and social interventions and even those that may be used additionally for complex use cases. A key determinant of consumer acceptance is a high-quality user-centric design for healthcare practitioners and pwMS. In pwMS, the different neurological disabilities should be considered, and particular attention must be paid to the course of the treatment and the safety processes of each treatment option. (4) Conclusion: Depending on the field of application and the respective users, interventions are designed for single, social, integrated or complex use. In order to be accepted by their target group, interventions must be beneficial and easy to use.

Leaf gas exchange and bean quality fluctuations over the whole canopy vertical profile of Arabic coffee cultivated under elevated CO2.

Leaves in different positions respond differently to dynamic fluctuations in light availability, temperature and to multiple environmental stresses. The current hypothesis states that elevated atmospheric CO2 (e[CO2]) can compensate for the negative effects of water scarcity regarding leaf gas exchanges and coffee bean quality traits over the canopy vertical profile, in interactions with light and temperature microclimate during the two final stages of berry development. Responses of Coffea arabica L. were observed in the 5th year of a free air CO2 enrichment experiment (FACE) under water-limited rainfed conditions. The light dependent leaf photosynthesis curves (A/PAR) were modelled for leaves sampled from vertical profile divided into four 50-cm thick layers. e[CO2] significantly increased gross photosynthesis (AmaxGross), the apparent quantum yield efficiency, light compensation point, light saturation point (LSP) and dark respiration rate (Rd). As a specific stage response, considering berry ripening, all parameters calculated from A/PAR were insensitive to leaf position over the vertical profile. Lack of a progressive increase in AmaxGross and LSP was observed over the whole canopy profile in both stages, especially in the two lowest layers, indicating leaf plasticity to light. Negative correlation of Rd to leaf temperature (TL) was observed under e[CO2] in both stages. Under e[CO2], stomatal conductance was also negatively correlated with TL, reducing leaf transpiration and Rd even with increasing TL. This indicated coffee leaf acclimation to elevated temperatures under e[CO2] and water restriction. The e[CO2] attenuation occurred under water restriction, especially in A and water use efficiency, in both stages, with the exception of the lowest two layers. Under e[CO2], coffee produced berries in moderate- and high light level layers, with homogeneous distribution among them, contrasted to the heterogeneous distribution under actual CO2. e[CO2] led to increased caffeine content in the highest layer, with reduction of chlorogenic acid and lipids under moderate light and to raised levels of sugar in the shaded low layer. The ability of coffee to respond to e[CO2] under limited soil water was expressed through the integrated individual leaf capacities to use the available light and water, resulting in final plant investments in new reproductive structures in moderate and high light level layers.

The influence of chemical composition diversity in the cooking quality of Andean bean genotypes.

Andean beans (Phaseolus vulgaris) chemical compositions and cooking characteristics contribute to a healthy diet. The objective of this study was to evaluate the influence of chemical composition on the cooking quality of 14 Andean beans genotypes with different seed coat colors. More specifically, water retention (WR), cooking time (CT), and solids released in the broth, were analysed. WR values ranged from 128.4% to 160.7% and CT ranged from 13.7 (BRS Embaixador) to 21.7 min (KID44). Andean beans showed variability in chemical composition, mainly starch content (39.43 g 100 g-1, BRS Realce to 51.92 g 100 g-1, LP15-04) and polymer composition. The profile of starch and interactions among minerals and chemical compounds influenced the cooking profiles than do the individual compounds. Andean beans traits of cooking, mainly CT, were influenced by their chemical composition; however they can be incorporated into diets without drastic changes in preparation methods.

Autophagy is not involved in lipid accumulation and the development of insulin resistance in skeletal muscle.

OBJECTIVE: To investigate the effect of high fat diet-induced insulin resistance on autophagy markers in the liver and skeletal muscle of mice in the fasted state and following an oral glucose bolus. METHODS: Forty C57BL/6J male mice were fed either a high fat, high sucrose (HFSD, n = 20) or standard chow control (CON, n = 20) diet for 16 weeks. Upon trial completion, mice were gavaged with water or glucose and skeletal muscle and liver were collected 15 min post gavage. Protein abundance and gene expression of autophagy markers and activation of related signalling pathways were assessed. RESULTS: Compared to CON, the HFSD intervention increased LC3B-II and p62/SQSTM1 protein abundance in the liver which is indicative of elevated autophagosome content via reduced clearance. These changes coincided with inhibitory autophagy signalling through elevated p-mTOR S2448 and p-ULK1S758. HFSD did not alter autophagy markers in skeletal muscle. Administration of an oral glucose bolus had no effect on autophagy markers or upstream signalling responses in either tissue regardless of diet. CONCLUSION: HFSD induces tissue-specific autophagy impairments, with autophagosome accumulation indicating reduced lysosomal clearance in the liver. In contrast, autophagy markers were unchanged in skeletal muscle, indicating that autophagy is not involved in the development of skeletal muscle insulin resistance.

Fear of falling and falls in people with multiple sclerosis: A literature review.

INTRODUCTION: Fear of falling (FOF) is a widespread problem affecting about 60% of people with multiple sclerosis (pwMS). Inflammatory lesions in the brain that are caused by the disease result in gait deficits and increase the risk of fall. Falls induce fear of falling and trigger a vicious circle, which in turn increases the likelihood of falling. Objective of this review was to provide an overview of existing research on the effects of FOF and therapy options in multiple sclerosis. METHODS: A systematic search at Web of Science and PubMed was conducted. The search included the terms (fear of falling) OR (concern about falling) OR (fall anxiety) AND (multiple sclerosis). RESULTS: In included studies, FOF was measured by different instruments. The Falls Efficacy Scale-International (FES-I) was the most frequently used instrument for pwMS. Patients with a higher FOF score fell more frequently, had lower walking speed, shorter stride length, larger ellipse sway area and a more severe disability. At present, therapeutic offers exist mainly in the field of physiotherapy. For reducing FOF, assisted vibration (dz = 0.68), VR (dz =0.87) and bicycle training (dz = 1.23) were the most effective methods. CONCLUSION: It is advisable to develop therapies that incorporate both physical and psychological aspects in neurorehabilitation, like in a cognitive behavioral therapy. Moreover, FOF monitoring should be integrated into the clinical routine.

The Dresden Protocol for Multidimensional Walking Assessment (DMWA) in Clinical Practice.

Walking impairments represent one of the most debilitating symptom areas for people with multiple sclerosis (MS). It is important to detect even slightest walking impairments in order to start and optimize necessary interventions in time to counteract further progression of the disability. For this reason, a regular monitoring through gait analysis is highly necessary. At advanced stages of MS with significant walking impairment, this assessment is also necessary to optimize symptomatic treatment, choose the most suitable walking aid and plan individualized rehabilitation. In clinical practice, walking impairment is only assessed at higher levels of the disease using e.g., the Expanded Disability Status Scale (EDSS). In contrast to the EDSS, standardized functional tests such as walking speed, walking endurance and balance as well as walking quality and gait-related patient-reported outcomes allow a more holistic and sensitive assessment of walking impairment. In recent years, the MS Center Dresden has established a standardized monitoring procedure for the routine multidimensional assessment of gait and balance disorders. In the following protocol, we present the techniques and procedures for the analysis of gait and balance of people with MS at the MS Center Dresden. Patients are assessed with a multidimensional gait analysis at least once a year. This enables long-term monitoring of walking impairment, which allows early active intervention regarding further progression of disease and improves the current standard clinical practice.

PtyNAMi: ptychographic nano-analytical microscope.

Ptychographic X-ray imaging at the highest spatial resolution requires an optimal experimental environment, providing a high coherent flux, excellent mechanical stability and a low background in the measured data. This requires, for example, a stable performance of all optical components along the entire beam path, high temperature stability, a robust sample and optics tracking system, and a scatter-free environment. This contribution summarizes the efforts along these lines to transform the nanoprobe station on beamline P06 (PETRA III) into the ptychographic nano-analytical microscope (PtyNAMi).

Indication of the geographical origin of honey using its physicochemical characteristics and multivariate analysis.

Honey from different botanical sources presents a great variability in chemical composition, physical properties, and sensorial attributes. The association between honey qualities and its geographical origin allows the recognition of honey, and beekeepers are economically benefited. The objective of this study was to evaluate the physicochemical characteristics of honey produced in Ortigueira, Brazil and to compare it with the honey produced in the neighboring localities for the request of geographical indication certification. In the 112 honey samples collected between 2010 and 2013 from Ortigueira and the neighboring localities, moisture acidity, pH, hydroxymethyl furfural (HMF), diastase activity (DA), sugars, proline (Pro), electrical conductivity (EC), color absorbance at 635 nm (C635), and Cielab color parameters were evaluated. HMF, reducing sugars (RS), total sugars (TS), proline, and color parameters (L*, a* and b*) were significantly different in Ortigueira 2010 honey seasons. Principal component analysis separated assapeixe (Vernonia sp) and capixingui (Croton floribundus) honeys from wild honeys (polyfloral). In addition, HMF, RS, L*, and lactonic acidity values promoted the separation between assapeixe and capixingui honeys. Ortigueira honey differs significantly from honeys from neighboring locality in pH, proline, HMF, DA, EC, RS, sucrose, TS, free and total acidity, and color parameters (C635, L*, a*, b*). The multivariate analysis applied to variables was efficient to discriminate honeys from different botanical sources and different locals, and is recommended for studies on the geographical indication of honey.

The Effect of Viscosity and Application Mode of Phosphoric Acid on Bond Strength of GlassFiber Post.

BACKGROUND: When a phosphoric acid is used, before applying an adhesive system, it is known that obtaining an effective adhesion to the root canal walls is a challenge. The aim of the present study was to evaluate the influence of phosphoric acid viscosity and application mode on the push-out bond strength (BS) values of fiberglass post to root dentin. The conditioning pattern on the root dentin was also evaluated. MATERIALS AND METHODS: The roots of 44 endodontically treated premolars were divided into 4 groups, of eleven teeth each, according to the combination of the main factors: phosphoric acid viscosity (liquid or gel) and application mode (passive or sonic). After application of the two-step etch-and-rinse adhesive system, the fiberglass posts were cemented with a dual-cure resin-cement. Roots were sectioned transversely into six 1-mm slices for push-out BS test at 0.5 mm/min. Some roots of each group were selected for evaluation of the conditioning pattern by scanning electron microscopy. BS results (three-way ANOVA and Tukey's test) and the conditioning pattern (Kruskal-Wallis test and Mann-Whitney test) were statistically evaluated (α= 0.05). RESULTS: The highest BS value was observed with a liquid phosphoric acid under sonic application mode (p < 0.05), being all other groups similar to one another (p < 0.05). Also, the highest BS value was observed in the cervical third, followed by the medium and the apical thirds (p < 0.05). The sonic application produced better smear layer removal and opening of dentinal tubules for both viscosities (p = 0.015). CONCLUSION: A better bonding of fiberglass posts to root canals can be achieved when the post spaces are conditioned with a liquid phosphoric acid under sonic application.

Mapping the Associations of the Plasma Lipidome With Insulin Resistance and Response to an Oral Glucose Tolerance Test.

CONTEXT: Insulin resistance (IR) remains a global health challenge. Lipidomics offers an opportunity to identify biomarkers and better understand mechanisms of IR associated with abnormal lipid metabolism. OBJECTIVE: The objective of this article is to determine plasma lipid species associated with indices of IR and evaluate the lipidome response to an oral glucose tolerance test (OGTT). DESIGN AND SETTING: This study was community based and cross-sectional. PARTICIPANTS AND SAMPLE: Plasma samples (collected at 0 and 120 min during an OGTT) from nonobese, young adults age 18 to 34 years (n = 246) were analyzed using liquid chromatography-tandem mass spectrometry. MAIN OUTCOME MEASURES: The associations between indices of IR and lipid classes and species (with a sex interaction term), or changes in lipid levels during an OGTT, were tested using linear models (adjusted for age, sex, body mass index, total cholesterol, high-density lipoprotein cholesterol, and triglycerides). RESULTS: Some (213) and (199) lipid species were associated with the homeostatic model assessment of insulin resistance and insulin area under curve (AUC), respectively. Alkylphosphatidylcholine (10), alkenylphosphatidylcholine (23), and alkylphosphatidylethanolamine (6) species were associated with insulin AUC in men only. Species of phosphatidylcholine (7) and sphingomyelin (5) were associated in women only. In response to an OGTT, a perturbation in the plasma lipidome, particularly in acylcarnitine species, was observed; and the changes in many lipid species were associated with insulin AUC. CONCLUSIONS: The plasma lipidome and changes in lipid levels during an OGTT were associated with indices of IR. These findings underlie the involvement of molecular lipid species in the pathogenesis of IR and possibly crosstalk between IR and sex-specific regulation of lipid metabolism.

Mechanisms of hyperinsulinaemia in apparently healthy non-obese young adults: role of insulin secretion, clearance and action and associations with plasma amino acids.

AIMS/HYPOTHESIS: This study aimed to examine the metabolic health of young apparently healthy non-obese adults to better understand mechanisms of hyperinsulinaemia. METHODS: Non-obese (BMI < 30 kg/m2) adults aged 18-35 years (N = 254) underwent a stable isotope-labelled OGTT. Insulin sensitivity, glucose effectiveness and beta cell function were determined using oral minimal models. Individuals were stratified into quartiles based on their insulin response during the OGTT, with quartile 1 having the lowest and quartile 4 the highest responses. RESULTS: Thirteen per cent of individuals had impaired fasting glucose (IFG; n = 14) or impaired glucose tolerance (IGT; n = 19), allowing comparisons across the continuum of insulin responses within the spectrum of normoglycaemia and prediabetes. BMI (~24 kg/m2) was similar across insulin quartiles and in those with IFG and IGT. Despite similar glycaemic excursions, fasting insulin, triacylglycerols and cholesterol were elevated in quartile 4. Insulin sensitivity was lowest in quartile 4, and accompanied by increased insulin secretion and reduced insulin clearance. Individuals with IFG had similar insulin sensitivity and beta cell function to those in quartiles 2 and 3, but were more insulin sensitive than individuals in quartile 4. While individuals with IGT had a similar degree of insulin resistance to quartile 4, they exhibited a more severe defect in beta cell function. Plasma branched-chain amino acids were not elevated in quartile 4, IFG or IGT. CONCLUSIONS/INTERPRETATION: Hyperinsulinaemia within normoglycaemic young, non-obese adults manifests due to increased insulin secretion and reduced insulin clearance. Individual phenotypic characterisation revealed that the most hyperinsulinaemic were more similar to individuals with IGT than IFG, suggesting that hyperinsulinaemic individuals may be on the continuum toward IGT. Furthermore, plasma branched-chain amino acids may not be an effective biomarker in identifying hyperinsulinaemia and insulin resistance in young non-obese adults.

Adult vascular dysfunction in foetal growth-restricted guinea-pigs is associated with a neonate-adult switching in Nos3 DNA methylation.

AIM: Foetal growth restriction (FGR) is associated with endothelial dysfunction and cardiovascular diseases in adult subjects. Early vascular remodelling and epigenetic changes occurring on key endothelial genes might precede this altered vascular function. Further, it has been proposed that oxidative stress during development may determine some of these epigenetic modifications. To address this issue, we studied the in vivo and ex vivo vascular function and Nos3 promoter DNA methylation in arteries from eight-month-old guinea-pig born from control, FGR-treated and FGR-NAC-treated pregnancies. METHODS: Femoral and carotid arteries in vivo vascular function were determined by Doppler, whilst ex vivo vascular function and biomechanical properties were assessed by wire myography. Levels of eNOS mRNA and site-specific DNA methylation in Nos3 promoter in aorta endothelial cells (AEC) were determined by qPCR and pyrosequencing respectively. RESULTS: FGR adult showed an increased femoral vascular resistance (P < .05), stiffness (P < .05) and arterial remodelling (P < .01), along with an impaired NO-mediated relaxation (P < .001). These effects were prevented by maternal treatment with NAC. Endothelial-NOS mRNA levels were decreased in FGR adult compared with control and FGR-NAC (P < .05), associated with increased DNA methylation levels (P < .01). Comparison of Nos3 DNA methylation in AEC showed a differential methylation pattern between foetal and adult guinea-pigs (P < .05). CONCLUSION: Altogether, these data suggest that adult vascular dysfunction in the FGR does not result from early changes in Nos3 promoter DNA methylation, but from an altered vessel structure established during foetal development.