Special Issue "Nutrition and the Function of the Central Nervous System"

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (15 February 2018).

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Prof. Dr. Billy R. Hammond
E-Mail Website
Guest Editor
Department of Psychology, University of Georgia, Athens, GA, USA
Tel. 706-542-4812; Fax: +1 706 542 3275
Interests: lutein; zeaxanthin; carotenoids; eye; retina; brain; vision; sensory
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue of Nutrients is focused on the role of nutrition in the development and maintenance of the central nervous system (CNS, primarily retina and brain).  This focus encompasses both nutritional effects on normal function and the prevention and treatment of CNS disease. The critical role of diet in most bodily systems (such as the cardiovascular or skeletal system) and in the prevention of disease (e.g., metabolic conditions, such as acquired diabetes) is largely accepted as an axiom.  It is only relatively recently, however, that researchers, particularly neuroscientists, began to focus on how diet influences the very organ system that is at the center of our self, the brain.  The retina is the most metabolically active tissue in the body and is impacted early by metabolic diseases such as diabetes.  The brain is some 2% of our mass but about 20–25% of inspired oxygen is delivered to this highly vascularized fatty (some 60% by volume) tissue. The CNS is not simply influenced by diet, it is built from, maintained, and preserved by diet. This premise is explored in this Special Issue.

Dr. Billy Hammond
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Central Nervous System
  • diet
  • gut-brain axis
  • carotenoids
  • neuroimaging

Published Papers (12 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle
The Food-Specific Serum IgG Reactivity in Major Depressive Disorder Patients, Irritable Bowel Syndrome Patients and Healthy Controls
Nutrients 2018, 10(5), 548; https://doi.org/10.3390/nu10050548 - 28 Apr 2018
Cited by 3
Abstract
There is an increasing amount of evidence which links the pathogenesis of irritable bowel syndrome (IBS) with food IgG hyperreactivity. Some authors have suggested that food IgG hyperreactivity could be also involved in the pathophysiology of major depressive disorder (MDD). The aim of [...] Read more.
There is an increasing amount of evidence which links the pathogenesis of irritable bowel syndrome (IBS) with food IgG hyperreactivity. Some authors have suggested that food IgG hyperreactivity could be also involved in the pathophysiology of major depressive disorder (MDD). The aim of this study was to compare levels of serum IgG against 39 selected food antigens between three groups of participants: patients with MDD (MDD group), patients with IBS (IBS group) and healthy controls (HC group). The study included 65 participants (22 in the MDD group, 22 in the IBS group and 21 in the HC group). Serum IgG levels were examined using enzyme-linked immunosorbent assay (ELISA). Medical records, clinical data and laboratory results were collected for the analysis. IgG food hyperreactivity (interpreted as an average of levels of IgG antibodies above 7.5 µg/mL) was detected in 28 (43%) participants, including 14 (64%) from the MDD group, ten (46%) from the IBS group and four (19%) from the HC group. We found differences between extreme IgG levels in MDD versus HC groups and in IBS versus HC groups. Patients with MDD had significantly higher serum levels of total IgG antibodies and IgG against celery, garlic and gluten compared with healthy controls. The MDD group also had higher serum IgG levels against gluten compared with the IBS group. Our results suggest dissimilarity in immune responses against food proteins between the examined groups, with the highest immunoreactivity in the MDD group. Further studies are needed to repeat and confirm these results in bigger cohorts and also examine clinical utility of IgG-based elimination diet in patients with MDD and IBS. Full article
Show Figures

Figure 1

Open AccessArticle
Lutein and Zeaxanthin Are Positively Associated with Visual–Spatial Functioning in Older Adults: An fMRI Study
Nutrients 2018, 10(4), 458; https://doi.org/10.3390/nu10040458 - 07 Apr 2018
Cited by 9
Abstract
Lutein (L) and zeaxanthin (Z) are two xanthophyll carotenoids that have antioxidant and anti-inflammatory properties. Previous work has demonstrated their importance for eye health and preventing diseases such as age-related macular degeneration. An emerging literature base has also demonstrated the importance of L [...] Read more.
Lutein (L) and zeaxanthin (Z) are two xanthophyll carotenoids that have antioxidant and anti-inflammatory properties. Previous work has demonstrated their importance for eye health and preventing diseases such as age-related macular degeneration. An emerging literature base has also demonstrated the importance of L and Z in cognition, neural structure, and neural efficiency. The present study aimed to better understand the mechanisms by which L and Z relate to cognition, in particular, visual–spatial processing and decision-making in older adults. We hypothesized that markers of higher levels of L and Z would be associated with better neural efficiency during a visual–spatial processing task. L and Z were assessed via standard measurement of blood serum and retinal concentrations. Visual–spatial processing and decision-making were assessed via a judgment of line orientation task (JLO) completed during a functional magnetic resonance imaging (fMRI) scan. The results demonstrated that individuals with higher concentrations of L and Z showed a decreased blood-oxygen-level dependent (BOLD) signal during task performance (i.e., “neural efficiency”) in key areas associated with visual–spatial perception, processing, decision-making, and motor coordination, including the lateral occipital cortex, occipital pole, superior and middle temporal gyri, superior parietal lobule, superior and middle frontal gyri, and pre- and post-central gyri. To our knowledge, this is the first investigation of the relationship of L and Z to visual–spatial processing at a neural level using in vivo methodology. Our findings suggest that L and Z may impact brain health and cognition in older adults by enhancing neurobiological efficiency in a variety of regions that support visual perception and decision-making. Full article
Show Figures

Figure 1

Open AccessArticle
Macular Xanthophylls Are Related to Intellectual Ability among Adults with Overweight and Obesity
Nutrients 2018, 10(4), 396; https://doi.org/10.3390/nu10040396 - 23 Mar 2018
Cited by 3
Abstract
Excess adiposity or obesity has been inversely related to cognitive function and macular xanthophyll status. However, whether the neuroprotective effects of macular xanthophylls on cognitive function are independent of excess adiposity is unclear. We investigated the relationship between macular xanthophylls and intellectual ability [...] Read more.
Excess adiposity or obesity has been inversely related to cognitive function and macular xanthophyll status. However, whether the neuroprotective effects of macular xanthophylls on cognitive function are independent of excess adiposity is unclear. We investigated the relationship between macular xanthophylls and intellectual ability among adults (N = 114) between 25 and 45 years with overweight and obesity (≥25 kg/m2). Dual energy X-ray absorptiometry and heterochromatic flicker photometry were used to assess whole body adiposity (%Fat) and macular pigment optical density (MPOD), respectively. Dietary xanthophylls (lutein and zeaxanthin) were assessed using 7-day diet records. The Kaufman Brief Intelligence Test-2 (KBIT-2) was used to assess general intelligence (IQ) as well as fluid and crystallized intelligence. Bivariate correlations revealed that MPOD was inversely related to %Fat and positively associated with IQ and fluid intelligence. Although %Fat was inversely correlated to IQ and fluid intelligence, this relationship did not persist following adjustment for sex and MPOD. Further, MPOD was an independent predictor of IQ and fluid intelligence. However, no significant relationships were observed between MPOD and crystalized intelligence. These results suggest that macular xanthophylls are selectively related to fluid intelligence, regardless of degree of adiposity among adults with overweight and obesity. Full article
Show Figures

Figure 1

Open AccessArticle
Dietary Sialyllactose Does Not Influence Measures of Recognition Memory or Diurnal Activity in the Young Pig
Nutrients 2018, 10(4), 395; https://doi.org/10.3390/nu10040395 - 23 Mar 2018
Cited by 6
Abstract
Sialic acid (SA) is an integral component of gangliosides and signaling molecules in the brain and its dietary intake may support cognitive development. We previously reported that feeding sialyllactose, a milk oligosaccharide that contains SA, alters SA content and diffusivity in the pig [...] Read more.
Sialic acid (SA) is an integral component of gangliosides and signaling molecules in the brain and its dietary intake may support cognitive development. We previously reported that feeding sialyllactose, a milk oligosaccharide that contains SA, alters SA content and diffusivity in the pig brain. The present research sought to expand upon such results and describe the effects of feeding sialyllactose on recognition memory and sleep/wake activity using a translational pig model. Pigs were provided ad libitum access to a customized milk replacer containing 0 g/L or 380 g/L of sialyllactose from postnatal day (PND) 2–22. Beginning on PND 15, pigs were fitted with accelerometers to track home-cage activity and testing on the novel object recognition task began at PND 17. There were no significant effects of diet on average daily body weight gain, average daily milk intake, or the gain-to-feed ratio during the study (all p ≥ 0.11). Pigs on both diets were able to display recognition memory on the novel object recognition task (p < 0.01), but performance and exploratory behavior did not differ between groups (all p ≥ 0.11). Total activity and percent time spent sleeping were equivalent between groups during both day and night cycles (all p ≥ 0.56). Dietary sialyllactose did not alter growth performance of young pigs, and there was no evidence that providing SA via sialyllactose benefits the development of recognition memory or gross sleep-related behaviors. Full article
Show Figures

Figure 1

Open AccessArticle
Claimed Effects, Outcome Variables and Methods of Measurement for Health Claims on Foods Related to Vision Proposed Under Regulation (EC) 1924/2006
Nutrients 2018, 10(2), 211; https://doi.org/10.3390/nu10020211 - 14 Feb 2018
Abstract
Adequate visual function has a strong impact on the quality of life of people. Several foods and food components have been hypothesized to play a role in the maintenance of normal visual function and in the prevention of eye diseases. Some of these [...] Read more.
Adequate visual function has a strong impact on the quality of life of people. Several foods and food components have been hypothesized to play a role in the maintenance of normal visual function and in the prevention of eye diseases. Some of these foods/food components have been the object of a request of authorization for use of health claims under Articles 13(5) or 14 of the Regulation (EC) 1924/2006. Most of these requests have received a negative opinion from the European Food Safety Authority (EFSA) due to the choice of inappropriate outcome variables (OVs) and/or methods of measurement (MMs) applied in the studies used to substantiate the claims. This manuscript refers to the collection, collation and critical analysis of OVs and MMs related to vision. Guidance document and requests for authorization of health claims were used to collect OVs and MMs related to vision. A literature review was performed to critically analyse OVs and MMs, with the aim of defining their appropriateness in the context of a specific claimed effect related to vision. The results highlight the importance of adequate choices of OVs and MMs for an effective substantiation of claims related to visual function. Full article
Open AccessArticle
The Macular Carotenoids are Associated with Cognitive Function in Preadolescent Children
Nutrients 2018, 10(2), 193; https://doi.org/10.3390/nu10020193 - 10 Feb 2018
Cited by 10
Abstract
The macular carotenoids lutein (L) and zeaxanthin (Z) are obtained via diet and accumulate in the central retina where they are referred to as macular pigment. The density of this biomarker (macular pigment optical density; MPOD) has been positively correlated with cognitive functioning [...] Read more.
The macular carotenoids lutein (L) and zeaxanthin (Z) are obtained via diet and accumulate in the central retina where they are referred to as macular pigment. The density of this biomarker (macular pigment optical density; MPOD) has been positively correlated with cognitive functioning via measures of global cognition, processing speed, and visual-spatial abilities, among others. Although improvements in cognitive function have been found in adults, much less is known about how L and Z intake may support or improve cognitive functioning during periods of rapid developmental change, such as childhood and pre-adolescence. This study examined the relationship between MPOD and cognitive functioning in 51 7–13-year-old children (51% female). MPOD was measured using heterochromatic flicker photometry (HFP) optimized for this age group. Cognitive function was assessed using the Woodcock-Johnson III (composite standard scores were obtained for Brief Intellectual Ability, Verbal Ability, Cognitive Efficiency, Processing Speed, and Executive Processes). In this sample, MPOD was significantly related to Executive Processes, r(47) = 0.288, p < 0.05, and Brief Intellectual Ability, r(47) = 0.268, p < 0.05. The relationship to Cognitive Efficiency was positive and trending but not significant, r(49) = 0.206, p = 0.074. In general, these data are consistent with those of adults showing a link between higher carotenoid status and improved cognitive functioning. Full article
Show Figures

Figure 1

Open AccessArticle
Early-Life Iron Deficiency Reduces Brain Iron Content and Alters Brain Tissue Composition Despite Iron Repletion: A Neuroimaging Assessment
Nutrients 2018, 10(2), 135; https://doi.org/10.3390/nu10020135 - 27 Jan 2018
Cited by 8
Abstract
Early-life iron deficiency has lifelong influences on brain structure and cognitive function, however characterization of these changes often requires invasive techniques. There is a need for non-invasive assessment of early-life iron deficiency with potential to translate findings to the human clinical setting. In [...] Read more.
Early-life iron deficiency has lifelong influences on brain structure and cognitive function, however characterization of these changes often requires invasive techniques. There is a need for non-invasive assessment of early-life iron deficiency with potential to translate findings to the human clinical setting. In this study, 28 male pigs were provided either a control diet (CONT; n = 14; 23.5 mg Fe/L milk replacer) or an iron-deficient diet (ID; n = 14; 1.56 mg Fe/L milk replacer) for phase 1 of the study, from postnatal day (PND) 2 until 32. Twenty pigs (n = 10/diet from phase 1 were used in phase 2 of the study from PND 33 to 61, where all pigs were provided a common iron-sufficient diet, regardless of their phase 1 dietary iron status. All pigs were subjected to magnetic resonance imaging at PND 32 and again at PND 61, and quantitative susceptibility mapping was used to assess brain iron content at both imaging time-points. Data collected on PND 61 were analyzed using voxel-based morphometry and tract-based spatial statistics to determine tissue concentration difference and white matter tract integrity, respectively. Quantitative susceptibility mapping outcomes indicated reduced iron content in the pons, medulla, cerebellum, left cortex, and left hippocampus of ID pigs compared with CONT pigs, regardless of imaging time-point. In contrast, iron contents were increased in the olfactory bulbs of ID pigs compared with CONT pigs. Voxel-based morphometric analysis indicated increased grey and white matter concentrations in CONT pigs compared with ID pigs that were evident at PND 61. Differences in tissue concentrations were predominately located in cortical tissue as well as the cerebellum, thalamus, caudate, internal capsule, and hippocampi. Tract-based spatial statistics indicated increased fractional anisotropy values along subcortical white matter tracts in CONT pigs compared with ID pigs that were evident on PND 61. All described differences were significant at p ≤ 0.05. Results from this study indicate that neuroimaging can sensitively detect structural and physiological changes due to early-life iron deficiency, including grey and white matter volumes, iron contents, as well as reduced subcortical white matter integrity, despite a subsequent period of dietary iron repletion. Full article
Show Figures

Figure 1

Open AccessArticle
Chronic Monosodium Glutamate Administration Induced Hyperalgesia in Mice
Nutrients 2018, 10(1), 1; https://doi.org/10.3390/nu10010001 - 21 Dec 2017
Cited by 5
Abstract
Monosodium glutamate (MSG) is a widely used food additive. Although it is generally considered safe, some questions regarding the impact of its use on general health have arisen. Several reports correlate MSG consumption with a series of unwanted reactions, including headaches and mechanical [...] Read more.
Monosodium glutamate (MSG) is a widely used food additive. Although it is generally considered safe, some questions regarding the impact of its use on general health have arisen. Several reports correlate MSG consumption with a series of unwanted reactions, including headaches and mechanical sensitivity in pericranial muscles. Endogenous glutamate plays a significant role in nociceptive processing, this neurotransmitter being associated with hyperalgesia and central sensitization. One of the mechanisms underlying these phenomena is the stimulation of Ca2+/calmodulin sensitive nitric oxide synthase, and a subsequent increase in nitric oxide production. This molecule is a key player in nociceptive processing, with implications in acute and chronic pain states. Our purpose was to investigate the effect of this food additive on the nociceptive threshold when given orally to mice. Hot-plate and formalin tests were used to assess nociceptive behaviour. We also tried to determine if a correlation between chronic administration of MSG and variations in central nitric oxide (NO) concentration could be established. We found that a dose of 300 mg/kg MSG given for 21 days reduces the pain threshold and is associated with a significant increase in brain NO level. The implications of these findings on food additive-drug interaction, and on pain perception in healthy humans, as well as in those suffering from affections involving chronic pain, are still to be investigated. Full article
Show Figures

Graphical abstract

Open AccessArticle
Dietary Sialyllactose Influences Sialic Acid Concentrations in the Prefrontal Cortex and Magnetic Resonance Imaging Measures in Corpus Callosum of Young Pigs
Nutrients 2017, 9(12), 1297; https://doi.org/10.3390/nu9121297 - 28 Nov 2017
Cited by 14
Abstract
Sialic acid (SA) is a key component of gangliosides and neural cell adhesion molecules important during neurodevelopment. Human milk contains SA in the form of sialyllactose (SL) an abundant oligosaccharide. To better understand the potential role of dietary SL on neurodevelopment, the effects [...] Read more.
Sialic acid (SA) is a key component of gangliosides and neural cell adhesion molecules important during neurodevelopment. Human milk contains SA in the form of sialyllactose (SL) an abundant oligosaccharide. To better understand the potential role of dietary SL on neurodevelopment, the effects of varying doses of dietary SL on brain SA content and neuroimaging markers of development were assessed in a newborn piglet model. Thirty-eight male pigs were provided one of four experimental diets from 2 to 32 days of age. Diets were formulated to contain: 0 mg SL/L (CON), 130 mg SL/L (LOW), 380 mg SL/L (MOD) or 760 mg SL/L (HIGH). At 32 or 33 days of age, all pigs were subjected to magnetic resonance imaging (MRI) to assess brain development. After MRI, pig serum and brains were collected and total, free and bound SA was analyzed. Results from this study indicate dietary SL influenced (p = 0.05) bound SA in the prefrontal cortex and the ratio of free SA to bound SA in the hippocampus (p = 0.04). Diffusion tensor imaging indicated treatment effects in mean (p < 0.01), axial (p < 0.01) and radial (p = 0.01) diffusivity in the corpus callosum. Tract-based spatial statistics (TBSS) indicated differences (p < 0.05) in white matter tracts and voxel-based morphometry (VBM) indicated differences (p < 0.05) in grey matter between LOW and MOD pigs. CONT and HIGH pigs were not included in the TBSS and VBM assessments. These findings suggest the corpus callosum, prefrontal cortex and hippocampus may be differentially sensitive to dietary SL supplementation. Full article
Show Figures

Figure 1

Open AccessArticle
Effects of a Lutein and Zeaxanthin Intervention on Cognitive Function: A Randomized, Double-Masked, Placebo-Controlled Trial of Younger Healthy Adults
Nutrients 2017, 9(11), 1246; https://doi.org/10.3390/nu9111246 - 14 Nov 2017
Cited by 16
Abstract
Background: Past studies have suggested that higher lutein (L) and zeaxanthin (Z) levels in serum and in the central nervous system (as quantified by measuring macular pigment optical density, MPOD) are related to improved cognitive function in older adults. Very few studies have [...] Read more.
Background: Past studies have suggested that higher lutein (L) and zeaxanthin (Z) levels in serum and in the central nervous system (as quantified by measuring macular pigment optical density, MPOD) are related to improved cognitive function in older adults. Very few studies have addressed the issue of xanthophylls and cognitive function in younger adults, and no controlled trials have been conducted to date to determine whether or not supplementation with L + Z can change cognitive function in this population. Objective: The purpose of this study was to determine whether or not supplementation with L + Z could improve cognitive function in young (age 18–30), healthy adults. Design: A randomized, double-masked, placebo-controlled trial design was used. Fifty-one young, healthy subjects were recruited as part of a larger study on xanthophylls and cognitive function. Subjects were randomized into active supplement (n = 37) and placebo groups (n = 14). MPOD was measured psychophysically using customized heterochromatic flicker photometry. Cognitive function was measured using the CNS Vital Signs testing platform. MPOD and cognitive function were measured every four months for a full year of supplementation. Results: Supplementation increased MPOD significantly over the course of the year, vs. placebo (p < 0.001). Daily supplementation with L + Z and increases in MPOD resulted in significant improvements in spatial memory (p < 0.04), reasoning ability (p < 0.05) and complex attention (p < 0.04), above and beyond improvements due to practice effects. Conclusions: Supplementation with L + Z improves CNS xanthophyll levels and cognitive function in young, healthy adults. Magnitudes of effects are similar to previous work reporting correlations between MPOD and cognition in other populations. Full article
Show Figures

Figure 1

Open AccessCommunication
The Gut Microbial Metabolite Trimethylamine-N-Oxide Is Present in Human Cerebrospinal Fluid
Nutrients 2017, 9(10), 1053; https://doi.org/10.3390/nu9101053 - 22 Sep 2017
Cited by 19
Abstract
Trimethylamine-N-oxide (TMAO) is a small organic molecule, derived from the intestinal and hepatic metabolism of dietary choline and carnitine. Although the involvement of TMAO in the framework of many chronic diseases has been recently described, no evidence on its putative role [...] Read more.
Trimethylamine-N-oxide (TMAO) is a small organic molecule, derived from the intestinal and hepatic metabolism of dietary choline and carnitine. Although the involvement of TMAO in the framework of many chronic diseases has been recently described, no evidence on its putative role in the central nervous system has been provided. The aim of this study was to evaluate whether TMAO is present at detectable levels in human cerebrospinal fluid (CSF). CSF was collected for diagnostic purposes from 58 subjects by lumbar puncture and TMAO was quantified by using liquid chromatography coupled with multiple-reaction monitoring mass spectrometry. The molecule was detected in all samples, at concentrations ranging between 0.11 and 6.43 µmol/L. Further analysis on CSF revealed that a total of 22 subjects were affected by Alzheimer’s disease (AD), 16 were affected by non-AD related dementia, and 20 were affected by other neurological disorders. However, the stratification of TMAO levels according to the neurological diagnoses revealed no differences among the three groups. In conclusion, we provide the first evidence that TMAO can be assessed in human CSF, but the actual impact of this dietary metabolite in the patho-physiolgy of the central nervous system requires further study. Full article
Show Figures

Figure 1

Review

Jump to: Research

Open AccessReview
Rationale for Dietary Antioxidant Treatment of ADHD
Nutrients 2018, 10(4), 405; https://doi.org/10.3390/nu10040405 - 24 Mar 2018
Cited by 3
Abstract
Increasing understanding arises regarding disadvantages of stimulant medication in children with ADHD (Attention-Deficit Hyperactivity Disorder). This review presents scientific findings supporting dietary antioxidant treatment of ADHD and describes substantial alterations in the immune system, epigenetic regulation of gene expression, and oxidative stress regulation [...] Read more.
Increasing understanding arises regarding disadvantages of stimulant medication in children with ADHD (Attention-Deficit Hyperactivity Disorder). This review presents scientific findings supporting dietary antioxidant treatment of ADHD and describes substantial alterations in the immune system, epigenetic regulation of gene expression, and oxidative stress regulation in ADHD. As a result, chronic inflammation and oxidative stress could develop, which can lead to ADHD symptoms, for example by chronic T-cell-mediated neuroinflammation, as well as by neuronal oxidative damage and loss of normal cerebral functions. Therefore, modulation of immune system activity and oxidant-antioxidant balance using nutritional approaches might have potential in ADHD treatment. The use of natural antioxidants against oxidative conditions is an emerging field in the management of neurodegenerative diseases. Dietary polyphenols, for example, have antioxidant capacities as well as immunoregulatory effects and, therefore, appear appropriate in ADHD therapy. This review can stimulate the development and investigation of dietary antioxidant treatment in ADHD, which is highly desired. Full article
Back to TopTop