The Effect of nutritional supplementation on subjective and objective measures of visual and retinal function:a random controlled trial

In industrialised countries age-related macular disease (ARMD) is the leading cause of visual loss in older people. Because oxidative stress is purported to be associated with an increased risk of disease development the role of antioxidant supplementation is of interest. Lutein is a carotenoid antioxidant that accumulates within the retina and is thought to filter blue light. Increased levels of lutein have been associated with reduced risk of developing ARMD and improvements in visual and retinal function in eyes with ARMD. The aim of this randomised controlled trial (RCT) was to investigate the effect of a lutein-based nutritional supplement on subjective and objective measures of visual function in healthy eyes and in eyes with age-related maculopathy (ARM) – an early form of ARMD. Supplement withdrawal effects were also investigated. A sample size of 66 healthy older (HO), healthy younger (HY), and ARM eyes were randomly allocated to receive a lutein-based supplement or no treatment for 40 weeks. The supplemented group then stopped supplementation to look at the effects of withdrawal over a further 20 weeks. The primary outcome measure was multifocal electroretinogram (mfERG) N1P1 amplitude. Secondary outcome measures were mfERG N1, P1 and N2 latency, contrast sensitivity (CS), Visual acuity (VA) and macular pigment optical density (MPOD). Sample sizes were sufficient for the RCT to have an 80% power to detect a significant clinical effect at the 5% significance level for all outcome measures when the healthy eye groups were combined, and CS, VA and mfERG in the ARM group. This RCT demonstrates significant improvements in MPOD in HY and HO supplemented eyes. When HY and HO supplemented groups were combined, MPOD improvements were maintained, and mfERG ring 2 P1 latency became shorter. On withdrawal of the supplement mfERG ring 1 N1P1 amplitude reduced in HO eyes. When HO and HY groups were combined, mfERG ring 1 and ring 2 N1P1 amplitudes were reduced. In ARM eyes, ring 3 N2 latency and ring 4 P1 latency became longer. These statistically significant changes may not be clinically significant. The finding that a lutein-based supplement increases MPOD in healthy eyes, but does not increase mfERG amplitudes contrasts with the CARMIS study and contributes to the debate on the use of nutritional supplementation in ARM.

Using empirical evidence of variations in worker performance to extend the capabilities of discrete event simulations in manufacturing

Discrete event simulation of manufacturing systems has become widely accepted as an important tool to aid the design of such systems. Often, however, it is applied by practitioners in a manner which largely ignores an important element of industry; namely, the workforce. Workers are usually represented as simple resources, often with deterministic performance values. This approach ignores the potentially large effect that human performance variation can have on a system. A long-term data collection exercise is described with the aim of quantifying the performance variation of workers in a typical automotive assembly plant. The data are presented in a histogram form which is immediately usable in simulations to improve the accuracy of design assessment. The results show levels of skewness and range which are far larger than anticipated by current researchers and practitioners in the field.

Evaluating the effect of splitting cylindrical power on improving patient tolerance to toric lens misalignment

Purpose: Evaluating the impact of splitting toric power on patient tolerance to misorientation such as with intraocular lens rotation. Setting: University vision clinic. Methods: Healthy, non astigmats had +1.50D astigmatism induced with spectacle lenses at 90°, 135°, 180° and +3.00D at 90°. Two correcting cylindrical lenses of the opposite sign and half the power each were subsequently added to the trial frame misaligned by 0°, 5° or 10° in a random order and misorientated from the initial axis in a clockwise direction by up to 15° in 5° steps. A second group of adapted astigmats with between 1.00 and 3.00DC had their astigmatism corrected with two toric spectacle lenses of half the power separated by 0°, 5° or 10° and misorientated from the initial axis in both directions by up to 15° in 5° steps. Distance, high contrast visual acuity was measured using a computerised test chart at each lens misalignment and misorientation. Results: Misorientation of the split toric lenses caused a statistically significant drop in visual acuity (F= 70.341; p< 0.001). Comparatively better acuities were observed around 180°, as anticipated (F= 3.775; p= 0.035). Misaligning the split toric power produced no benefit in visual acuity retention with axis misorientation when subjects had astigmatism induced with a low (F= 2.190, p= 0.129) or high cylinder (F= 0.491, p= 0.617) or in the adapted astigmats (F= 0.120, p= 0.887). Conclusion: Misalignment of toric lens power split across the front and back lens surfaces had no beneficial effect on distance visual acuity, but also no negative effect. © 2013 British Contact Lens Association.

The effect of simulated cataract light scatter on retinal vessel oximetry

To assess the impact of light scatter, similar to that introduced by cataract on retinal vessel blood oxygen saturation measurements using poly-bead solutions of varying concentrations. Eight healthy, young, non-smoking individuals were enrolled for this study. All subjects underwent digital blood pressure measurements, assessment of non-contact intraocular pressure, pupil dilation and retinal vessel oximetry using dual wavelength photography (Oximetry Module, Imedos Systems, Germany). To simulate light scatter, cells comprising a plastic collar and two plano lenses were filled with solutions of differing concentrations (0.001, 0.002 and 0.004%) of polystyrene microspheres (Polysciences Inc., USA). The adopted light scatter model showed an artifactual increase in venous optical density ratio (p=0.036), with the 0.004% condition producing significantly higher venous optical density ratio values when compared to images without a cell in place. Spectrophotometric analysis, and thus retinal vessel oximetry of the retinal vessels, is altered by artificial light scatter. © 2013 Elsevier Ltd.

Discrimination of healthy and cancer cells of the bladder by metabolic state, based on autofluorescence

Bladder cancer is among the most common cancers worldwide (4th in men). It is responsible for high patient morbidity and displays rapid recurrence and progression. Lack of sensitivity of gold standard techniques (white light cystoscopy, voided urine cytology) means many early treatable cases are missed. The result is a large number of advanced cases of bladder cancer which require extensive treatment and monitoring. For this reason, bladder cancer is the single most expensive cancer to treat on a per patient basis. In recent years, autofluorescence spectroscopy has begun to shed light into disease research. Of particular interest in cancer research are the fluorescent metabolic cofactors NADH and FAD. Early in tumour development, cancer cells often undergo a metabolic shift (the Warburg effect) resulting in increased NADH. The ratio of NADH to FAD ("redox ratio") can therefore be used as an indicator of the metabolic status of cells. Redox ratio measurements have been used to differentiate between healthy and cancer breast cells and to monitor cellular responses to therapies. Here, we have demonstrated, using healthy and bladder cancer cell lines, a statistically significant difference in the redox ratio of bladder cancer cells, indicative of a metabolic shift. To do this we customised a standard flow cytometer to excite and record fluorescence specifically from NADH and FAD, along with a method for automatically calculating the redox ratio of individual cells within large populations. These results could inform the design of novel probes and screening systems for the early detection of bladder cancer.

Altered resting-state EEG source functional connectivity in schizophrenia:the effect of illness duration

Despite the increasing body of evidence supporting the hypothesis of schizophrenia as a disconnection syndrome, studies of resting-state EEG Source Functional Connectivity (EEG-SFC) in people affected by schizophrenia are sparse. The aim of the present study was to investigate resting-state EEG-SFC in 77 stable, medicated patients with schizophrenia (SCZ) compared to 78 healthy volunteers (HV). In order to study the effect of illness duration, SCZ were divided in those with a short duration of disease (SDD; n = 25) and those with a long duration of disease (LDD; n = 52). Resting-state EEG recordings in eyes closed condition were analyzed and lagged phase synchronization (LPS) indices were calculated for each ROI pair in the source-space EEG data. In delta and theta bands, SCZ had greater EEG-SFC than HV; a higher theta band connectivity in frontal regions was observed in LDD compared with SDD. In the alpha band, SCZ showed lower frontal EEG-SFC compared with HV whereas no differences were found between LDD and SDD. In the beta1 band, SCZ had greater EEG-SFC compared with HVs and in the beta2 band, LDD presented lower frontal and parieto-temporal EEG-SFC compared with HV. In the gamma band, SDD had greater connectivity values compared with LDD and HV. This study suggests that resting state brain network connectivity is abnormally organized in schizophrenia, with different patterns for the different EEG frequency components and that EEG can be a powerful tool to further elucidate the complexity of such disordered connectivity.

The effect of ocular nutritional supplements on macular pigment optical density

This thesis describes the investigation of the effects of ocular supplements with different levels of nutrients on the macular pigment optical density (MPOD) in participants with healthy eyes. Abstract A review of the literature highlighted that ocular supplements are produced in various combinations of nutrients and concentrations. The ideal concentrations of nutrients such as lutein (L) have not been established. It was unclear whether different stages of eye disease require different concentrations of key nutrients, leading to the design of this study. The primary aim was to determine the effects of ocular supplements with different concentrations of nutrients on the MPOD of healthy participants. The secondary aim was to determine L and zeaxanthin (Z) intake at the start and end of the study through completion of food diaries. The primary study was split into two experiments. Experiment 1 was an exploratory study to determine sample size and experiment 2 the main study. Statistical power was calculated and a sample size of 38 was specified. Block stratification for age, gender and smoking habit was applied and from 101 volunteers 42 completed the study, 31 with both sets of food diaries. Four confounders were accounted for in the design of the study; gender, smoking habit, age and diet. Further factors that could affect comparability of results between studies were identified during the study and were not monitored; ethnicity, gastro-intestinal health, alcohol intake, body mass index and genetics. Comparisons were made between the sample population and the Sheffield general population according to recent demographic results in the public domain. Food diaries were analysed and shown to have no statistical difference when comparing baseline to final results. The average L and Z intake for the 31 participants who returned both sets of food diaries was initially 1.96mg and 1.51mg for the final food diaries. The effect of the two ocular supplements with different levels of xanthophyll (6mg lutein/zeaxanthin and 10mg lutein only) on MPOD was not significantly different over a four-month period.

The effect of whole body vibration on oxygen uptake and electromyographic signal of the rectus femoris muscle during static and dynamic squat

Whole Body Vibrations consist of a vibration stimulus mechanically transferred to the body. The impact of vibration treatment on specific muscular activity, neuromuscular, and postural control has been widely studied. We investigated whole body vibration (WBV) effect on oxygen uptake and electromyographic signal of the rectus femoris muscle during static and dynamic squat. Fourteen healthy subjects performed a static and dynamic squat with and without vibration. During the vibration exercises, a significant increase was found in oxygen uptake (P=0.05), which increased by 44% during the static squat and 29.4% during the dynamic squat. Vibration increased heart rate by 11.1 ± 9.1 beats.min-1 during the static squat and 7.9 ± 8.3 beats.min-1 during the dynamic squat. No significant changes were observed in rate of perceived exertion between the exercises with and without vibration. The results indicate that the static squat with WBV produced higher neuromuscular and cardiorespiratory system activation for exercise duration ?60 sec. Otherwise, if the single bout duration was higher than 60 sec, the greater cardiorespiratory system activation was achieved during the dynamic squat with WBV while higher neuromuscular activation was still obtained with the static exercise.

Placebo expectancy effect of consuming psychoactive beverages on cognition and mood

Energy drinks have become very popular over the past few years with over half the student population in colleges and universities consuming them at least once a month (Malinauskas et al., 2007). It has been reported that the most common reasons why students consume energy drinks are to maintain alertness, reduce symptoms of hangover, increase energy, to help with driving and to prevent sleepiness (Attila and Cakir, 2011; Malinauskas et al., 2007). Previous research has suggested that energy drinks enhance sensorimotor speed, behaviour, and reduce levels of fatigue (Alford et al., 2001; Horne and Reyner, 2001; Howard and Marczinski, 2010; Kennedy and Scholey, 2004; Smit et al., 2004). The two key ingredients found in energy drinks are caffeine and glucose which have been examined together and alone, which have indicated enhanced reaction times, improvement in both verbal memory and sustained attention and more recently there is evidence to show that expectancy may play a key role in predicting intentions of future consumption (Adan and serra-Grabulosa, 2010). According to Kirsch (1997) people have specific expectations when they consume psychoactive substances that trigger physiological and psychological reactions, which tend to be independent of the psychoactive substance ingested. The concept of expectancy effects can be unambiguous especially when the information provided to the participants prior to the experimental study is specific to a possible outcome response. This thesis investigated the extent of expectancy effect on cognition and mood when psychoactive drinks containing caffeine and glucose were consumed in comparison to non-psychoactive drinks. The investigation commenced with examining the independent effects of caffeine and glucose, followed by the combination of caffeine and glucose as an energy drink on mood and cognition. The investigation advanced by comparing drink presentation effects (i.e., consuming the experimental drink from a branded bottle versus from a glass) irrespective of drink content on mood and cognition. Finally, the investigation lead to exploring what factors may predict expectancy effects when participants’ consumed psychoactive drinks among healthy adults. This was done by applying the Theory of Planned Behaviour model (TPB) (Azjen, 1991) to explore the contribution of specific attitudes, subjective norms and perceived behavioural control to the extent of expectancy effects as well as to behavioural intention, with additional variables including; beliefs, habits, past-behaviour, selfidentity. Self-identity representing someone who drinks energy drinks regularly. The level of internal consistency for Cronbach’s alpha was conducted for each variable within the TPB model and for the additional variables included for test reliability. This thesis consisted of four studies, which found that consumption of caffeine and glucose independently and also in combination resulted in psychoactive effects on mood and cognition. Experiment 2 was the only study, which indicated an expectancy effect for immediate verbal recall task and the mood subscale tension. Conversely, for experiment 4 there was a reverse effect found for the immediate verbal recall task. However, there were significant expectancy and psychoactive effects found for mood subscales throughout the four studies. It was also found that the TPB model had two significant variables past-behaviour and self-identity predicted intentions suggesting that participants who regularly consume psychoactive beverages have salient beliefs about consuming psychoactive drinks and the TPB model can be utilised to predict their intentions. Furthermore, the Theory of planned behaviour model found that habit and self-identity significantly predicted participants’ expectancy effects on the vigour. Indicating consumers of energy drinks are familiar with expected outcome response. This model was unsuccessful in predicting expectancy response for cognitive performance. Thus, overall the findings from the four studies indicated that caffeine and glucose have cognitive enhancing properties, which also positively improve mood. However, expectancy effects have been identified for mood only, whereas the overall findings within this thesis were unable to identify significant predictors of expectancy effect and response.

Investigating the role of parent and child characteristics in healthy eating intervention outcomes

While numerous studies have investigated the efficacy of interventions at increasing children's vegetable consumption, little research has examined the effect of individual characteristics on intervention outcomes. In previous research, interventions consisting of modelling and rewards have been shown to increase children's vegetable intake, but differences were identified in terms of how much children respond to such interventions. With this in mind, the current study investigated the role of parental feeding practices, child temperament, and child eating behaviours as predictors of intervention success. Parents (N = 90) of children aged 2-4 years were recruited from toddler groups across Leicestershire, UK. Parents completed measures of feeding practices, child eating behaviours and child temperament, before participating in one of four conditions of a home-based, parent led 14 day intervention aimed at increasing their child's consumption of a disliked vegetable. Correlations and logistic regressions were performed to investigate the role of these factors in predicting intervention success. Parental feeding practices were not significantly associated with intervention success. However, child sociability and food fussiness significantly predicted intervention success, producing a regression model which could predict intervention success in 61% of cases. These findings suggest that future interventions could benefit from being tailored according to child temperament. Furthermore, interventions for children high in food fussiness may be better targeted at reducing fussiness in addition to increasing vegetable consumption.

The role of supraspinal excitability in the development of healthy-limb deficits following anterior cruciate ligament injury

In the current study, we examined how supraspinal and spinal excitability were altered bilaterally after unilateral anterior cruciate ligament reconstruction (ACLr). 7 participants with ACLr and 7 healthy controls underwent transcranial magnetic stimulation (TMS) and electrical stimulation. To evaluate supraspinal excitability, resting motor thresholds (RMT) and motor evoked potential (MEP) stimulus response curves (SRC) were used. To measure spinal excitability, H-reflex SRC gain was assessed. Mixed factorial ANOVAs were used to compare measures between limbs and between groups. Cohen’s d was used to assess effect sizes between groups. Data indicated no significant differences between subject groups or between limbs. However, large effect sizes were found between limbs for H-reflex gain and RMTs suggesting that ACLr can have an effect on some of the variables examined. This study identified decreases in strength in the injured limbs and that subjects with an ACL injury exhibited decreases in spinal and supraspinal excitability of the quadriceps compared to Healthy controls.

The dual effect of normobaric hypoxia on heart rate variability and substrate partitioning following interval cycling

Recent studies have shown the importance of the beat-by-beat changes in heart rate influenced by the autonomic nervous system (ANS), or heart rate variability (HRV). The purpose of this study was to examine the lasting effects of hypoxic exercise on HRV, and its influences on substrate usage. Results from this study could lead an increased understanding on this topic. Eight active healthy males (age: 31±11 years; height: 180±7 cm; weight: 83±8 kg; VO₂max (maximal oxygen consumption): 4.4±0.6 L•min⁻¹) underwent normoxic and hypoxic (FᵢO₂= 0.15) conditions during high-intensity interval (HIIT) cycling (70%-high interval, 35%-rest interval). Cycling intensity was determined by a peak power output cycling test. Each experimental session consisted of a basal metabolic rate determination, up to 45-minutes of HIIT cycling, and three 30-minute post-exercise metabolic rate measurements (spanning 3 hours and 15 minutes after exercise). During exercise, RPE was higher (p<0.01) and LAC (lactate) increased (p=0.001) at each point of time in hypoxia, with no change in normoxia. After hypoxic exercise, the SNS/PNS ratio (overall ANS activity) was significantly higher (p<0.01) and significantly decreased through time in both conditions (p<0.01). In addition, a significant interaction between time and conditions (p<0.02) showed a decrease in LAC concentration through time post-hypoxic exercise. The findings showed that a single bout of hypoxic exercise alters ANS activity post-exercise along with shifting substrate partitioning from glycolytic to lipolytic energy production. The significant decrease in LAC concentration post-hypoxic exercise supports the notion that hypoxic HIIT induces a greater muscle glycogen depletion leading to increased fat oxidation to sustain glycogenesis and gluconeogenesis to maintain blood glucose level during recovery.

Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans.

OBJECTIVE: The orexigenic gut hormone ghrelin and its receptor are present in pancreatic islets. Although ghrelin reduces insulin secretion in rodents, its effect on insulin secretion in humans has not been established. The goal of this study was to test the hypothesis that circulating ghrelin suppresses glucose-stimulated insulin secretion in healthy subjects. RESEARCH DESIGN AND METHODS: Ghrelin (0.3, 0.9 and 1.5 nmol/kg/h) or saline was infused for more than 65 min in 12 healthy patients (8 male/4 female) on 4 separate occasions in a counterbalanced fashion. An intravenous glucose tolerance test was performed during steady state plasma ghrelin levels. The acute insulin response to intravenous glucose (AIRg) was calculated from plasma insulin concentrations between 2 and 10 min after the glucose bolus. Intravenous glucose tolerance was measured as the glucose disappearance constant (Kg) from 10 to 30 min. RESULTS: The three ghrelin infusions raised plasma total ghrelin concentrations to 4-, 15-, and 23-fold above the fasting level, respectively. Ghrelin infusion did not alter fasting plasma insulin or glucose, but compared with saline, the 0.3, 0.9, and 1.5 nmol/kg/h doses decreased AIRg (2,152 +/- 448 vs. 1,478 +/- 2,889, 1,419 +/- 275, and 1,120 +/- 174 pmol/l) and Kg (0.3 and 1.5 nmol/kg/h doses only) significantly (P < 0.05 for all). Ghrelin infusion raised plasma growth hormone and serum cortisol concentrations significantly (P < 0.001 for both), but had no effect on glucagon, epinephrine, or norepinephrine levels (P = 0.44, 0.74, and 0.48, respectively). CONCLUSIONS: This is a robust proof-of-concept study showing that exogenous ghrelin reduces glucose-stimulated insulin secretion and glucose disappearance in healthy humans. Our findings raise the possibility that endogenous ghrelin has a role in physiologic insulin secretion, and that ghrelin antagonists could improve beta-cell function.

The effect of gestational and lactational age on the human milk metabolome

Human milk is the ideal nutrition source for healthy infants during the first six months of life and a detailed characterisation of the composition of milk from mothers that deliver prematurely (<37 weeks gestation), and of how human milk changes during lactation, would benefit our understanding of the nutritional requirements of premature infants. Individual milk samples from mothers delivering prematurely and at term were collected. The human milk metabolome, established by (NMR) spectroscopy, was influenced by gestational and lactation age. Metabolite profiling identified that levels of valine, leucine, betaine, and creatinine were increased in colostrum from term mothers compared with mature milk, while those of glutamate, caprylate, and caprate were increased in mature term milk compared with colostrum. Levels of oligosaccharides, citrate, and creatinine were increased in pre-term colostrum, while those of caprylate, caprate, valine, leucine, glutamate, and pantothenate increased with time postpartum. There were differences between pre-term and full-term milk in the levels of carnitine, caprylate, caprate, pantothenate, urea, lactose, oligosaccharides, citrate, phosphocholine, choline, and formate. These findings suggest that the metabolome of pre-term milk changes within 5-7 weeks postpartum to resemble that of term milk, independent of time of gestation at pre-mature delivery.

THE EFFECT OF PREECLAMPSIA ON RENAL FUNCTION: CROSS-SECTIONAL STUDIES OF POSTPARTUM PREECLAMPTICS AND WOMEN WHO WERE DESTINED TO DEVELOP PREECLAMPSIA

Preeclampsia (PE) is a pregnancy complication that is new-onset of hypertension and proteinuria after 20 weeks of gestation. However, subclinical renal dysfunction may be apparent earlier in gestation prior to the clinical presentation of PE. Although the maternal syndrome of PE resolves early postpartum, women with a history of PE are at higher risk of renal dysfunction later in life. Mineral metabolism, such as phosphate balance is heavily dependent on renal function, yet, phosphate handling in women with a history of PE is largely unknown. To investigate whether women with a history of PE would exhibit changes in phosphate metabolism compared to healthy parous women, phosphate loading test was used. Women with or without a history of PE, who were 6 months to 5 years postpartum, were recruited for this study. Blood and urine samples were collected before and after the oral dosing of 500mg phosphate solution. Biochemical markers of phosphate metabolism and renal function were evaluated. In order to assess the difference in renal function alteration between first trimester women who were or were not destined to develop PE, plasma cystatin C concentration was analysed. After phosphate loading, women with a history of PE had significantly elevated serum phosphate at both 1- and 2-hour, while controls had higher urine phosphate:urine creatinine excretion ratio at 1-hour than women with a history of PE. Women with a history of PE had no changes in intact parathyroid hormone (iPTH) concentration throughout the study period, whereas controls had elevated iPTH at 1-hour from baseline. In terms of renal function in the first trimester, there was no difference in plasma cystatin C concentration between women who were or were not destined to develop PE. The elevation of serum phosphate in women with a history of PE could be due to the delay in phosphate excretion. Prolong elevation of serum phosphate can have serious consequences later in life. Thus, oral phosphate challenge may serve as a useful method of early screening for altered phosphate metabolism and renal function.