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Title:
Effect of low-fat diet interventions versus other diet interventions on long-term weight change in adults: a systematic review and meta-analysis.
Authors:
Tobias, Deirdre K.; Chen, Mu; Manson, JoAnn E.; Ludwig, David S.; Willett, Walter; Hu, Frank B.
Abstract:
BACKGROUND: The effectiveness of low-fat diets for long-term weight loss has been debated for decades, with many randomised controlled trials (RCTs) and recent reviews giving mixed results. We aimed to summarise the large body of evidence from RCTs to determine whether low-fat diets contribute to greater weight loss than participants' usual diet, low-carbohydrate diets, and other higher-fat dietary interventions. METHODS: We did a systematic review and random effects meta-analysis of RCTs comparing the long-term effect (>/=1 year) of low-fat and higher-fat dietary interventions on weight loss by searching MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews to identify eligible trials published from database inception up until July 31, 2014. We excluded trials if one intervention group included a non-dietary weight loss component but the other did not, and trials of dietary supplements or meal replacement drink interventions. Data including the main outcome measure of mean difference in weight change between interventions, and whether interventions were intended to lead to weight loss, weight maintenance, or neither, were extracted from published reports. We estimated the pooled weighted mean difference (WMD) with a DerSimonian and Laird random effects method. FINDINGS: 3517 citations were identified by the search and 53 studies met our inclusion criteria, including 68 128 participants (69 comparisons). In weight loss trials, low-carbohydrate interventions led to significantly greater weight loss than did low-fat interventions (18 comparisons; WMD 1.15 kg [95% CI 0.52 to 1.79]; I(2)=10%). Low-fat interventions did not lead to differences in weight change compared with other higher-fat weight loss interventions (19 comparisons; WMD 0.36 kg [-0.66 to 1.37; I(2)=82%), and led to a greater weight decrease only when compared with a usual diet (eight comparisons; -5.41 kg [-7.29 to -3.54]; I(2)=68%). Similarly, results of non-weight-loss trials and weight maintenance trials, for which no low-carbohydrate comparisons were made, showed that low-fat versus higher-fat interventions have a similar effect on weight loss, and that low-fat interventions led to greater weight loss only when compared with usual diet. In weight loss trials, higher-fat weight loss interventions led to significantly greater weight loss than low-fat interventions when groups differed by more than 5% of calories obtained from fat at follow-up (18 comparisons; WMD 1.04 kg [95% CI 0.06 to 2.03]; I(2)=78%), and when the difference in serum triglycerides between the two interventions at follow-up was at least 0.06 mmol/L (17 comparisons; 1.38 kg [0.50 to 2.25]; I(2)=62%). INTERPRETATION: These findings suggest that the long-term effect of low-fat diet intervention on bodyweight depends on the intensity of the intervention in the comparison group. When compared with dietary interventions of similar intensity, evidence from RCTs does not support low-fat diets over other dietary interventions for long-term weight loss. FUNDING: National Institutes of Health and American Diabetes Association.
Published:
2015-12
Title:
Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial
Authors:
Lenze, Eric J; Mulsant, Benoit H; Blumberger, Daniel M; Karp, Jordan F; Newcomer, John W; Anderson, Stewart J; Dew, Mary Amanda; Butters, Meryl A; Stack, Jacqueline A; Begley, Amy E; Reynolds, Charles F
Abstract:
Background Treatment-resistant major depression is common and potentially life-threatening in elderly people, in whom little is known about the benefits and risks of augmentation pharmacotherapy. We aimed to assess whether aripiprazole is associated with a higher probability of remission than is placebo.
Published:
2015-12
Title:
Food Preference Patterns in a UK Twin Cohort
Authors:
Pallister, Tess; Sharafi, Mastaneh; Lachance, Genevieve; Pirastu, Nicola; Mohney, Robert P.; MacGregor, Alex; Feskens, Edith J. M.; Duffy, Valerie; Spector, Tim D.; Menni, Cristina
Abstract:
Food liking-disliking patterns may strongly influence food choices and health. Here we assess: (1) whether food preference patterns are genetic/environmentally driven; and (2) the relationship between metabolomics profiles and food preference patterns in a large population of twins. 2,107 individuals from TwinsUK completed an online food and lifestyle preference questionnaire. Principle components analysis was undertaken to identify patterns of food liking-disliking. Heritability estimates for each liking pattern were obtained by structural equation modeling. The correlation between blood metabolomics profiles (280 metabolites) and each food liking pattern was assessed in a subset of 1,491 individuals and replicated in an independent subset of monozygotic twin pairs discordant for the liking pattern (65 to 88 pairs). Results from both analyses were meta-analyzed. Four major food-liking patterns were identified (Fruit and Vegetable, Distinctive Tastes, Sweet and High Carbohydrate, and Meat) accounting for 26% of the total variance. All patterns were moderately heritable (Fruit and Vegetable, h2[95% CI]: 0.36 [0.28; 0.44]; Distinctive Tastes: 0.58 [0.52; 0.64]; Sweet and High Carbohydrate: 0.52 [0.45, 0.59] and Meat: 0.44 [0.35; 0.51]), indicating genetic factors influence food liking-disliking. Overall, we identified 14 significant metabolite associations (Bonferroni p
Published:
2015-12
Title:
Impact of preoperative fasting times on blood glucose concentration, ketone bodies and acid-base balance in children younger than 36 months: A prospective observational study
Authors:
Dennhardt, Nils; Beck, Christiane; Huber, Dirk; Nickel, Katja; Sander, Björn; Witt, Lars-Henrik; Boethig, Dietmar; Sümpelmann, Robert
Abstract:
BACKGROUND: In contrast to preoperative fasting guidelines in paediatric anaesthesia, actual fasting times are often too long. OBJECTIVE: The objective of this study was to evaluate the effect of preoperative fasting on glucose concentration, ketone bodies and acid-base balance in children. DESIGN: A prospective, noninterventional, clinical observational study. SETTING: A single-centre trial, study period from June 2014 to November 2014. PATIENTS: One hundred children aged 0 to 36 months scheduled for elective paediatric surgery. MAIN OUTCOME MEASURES: Patient demographics, fasting times, haemodynamic data, glucose and ketone body concentrations, and acid-base parameters after induction of anaesthesia were documented using a standardised case report form. RESULTS: Mean fasting period was 7.8 ± 4.5 (3.5 to 20) h, and deviation from guideline (ΔGL) was 3.3 ± 3.2 (-2 to 14) h. Linear regression showed a significant correlation between fasting times and ketone bodies, anion gap, base excess, osmolality as well as bicarbonate (for each, P < 0.05), but not glucose or lactate. In children with ΔGL more than 2 h (54%), ketone bodies, osmolality and anion gap were significantly higher and base excess significantly lower than children with ΔGL less than 2 h (for each, P
Published:
2015-12
Title:
Internet Addiction and Attention Deficit Hyperactivity Disorder Among Schoolchildren
Authors:
Weinstein, Aviv; Yaacov, Yafa; Manning, Michal; Danon, Pinhas; Weizman, Abraham
Abstract:
BACKGROUND: Use of the internet and videogames by children and adolescents has risen dramatically over the last decade. Increasing evidence of internet and videogame addiction among children is causing concern due to its harmful physical, emotional and social consequences. There is also emerging evidence for an association between computer and videogame addiction and attention deficit/hyperactivity disorder (ADHD). OBJECTIVES: To investigate the relationship between ADHD and internet addiction. METHODS: We compared 50 male schoolchildren, mean age 13 years, diagnosed with ADHD to 50 male schoolchildren without ADHD on measures of internet addiction, internet use and sleep patterns. RESULTS: Children with ADHD had higher scores on the Internet Addiction Test (IAT), used the internet for longer hours, and went to sleep later than those without ADHD. CONCLUSIONS: These findings indicate an association of ADHD, sleep disorders and internet/videogame addiction.
Published:
2015-12
Title:
Longitudinal Metabolomic Profiling of Amino Acids and Lipids across Healthy Pregnancy
Authors:
Lindsay, Karen L.; Hellmuth, Christian; Uhl, Olaf; Buss, Claudia; Wadhwa, Pathik D.; Koletzko, Berthold; Entringer, Sonja
Abstract:
Pregnancy is characterized by a complexity of metabolic processes that may impact fetal development and ultimately, infant health outcomes. However, our understanding of whole body maternal and fetal metabolism during this critical life stage remains incomplete. The objective of this study is to utilize metabolomics to profile longitudinal patterns of fasting maternal metabolites among a cohort of non-diabetic, healthy pregnant women in order to advance our understanding of changes in protein and lipid concentrations across gestation, the biochemical pathways by which they are metabolized and to describe variation in maternal metabolites between ethnic groups. Among 160 pregnant women, amino acids, tricarboxylic acid (TCA) cycle intermediates, keto-bodies and non-esterified fatty acids were detected by liquid chromatography coupled with mass spectrometry, while polar lipids were detected through flow-injected mass spectrometry. The maternal plasma concentration of several essential and non-essential amino acids, long-chain polyunsaturated fatty acids, free carnitine, acetylcarnitine, phosphatidylcholines and sphingomyelins significantly decreased across pregnancy. Concentrations of several TCA intermediates increase as pregnancy progresses, as well as the keto-body β-hydroxybutyrate. Ratios of specific acylcarnitines used as indicators of metabolic pathways suggest a decreased beta-oxidation rate and increased carnitine palmitoyltransferase-1 enzyme activity with advancing gestation. Decreasing amino acid concentrations likely reflects placental uptake and tissue biosynthesis. The absence of any increase in plasma non-esterified fatty acids is unexpected in the catabolic phase of later pregnancy and may reflect enhanced placental fatty acid uptake and utilization for fetal tissue growth. While it appears that energy production through the TCA cycle increases as pregnancy progresses, decreasing patterns of free carnitine and acetylcarnitine as well as increased carnitine palmitoyltransferase-1 rate and β-hydroxybutyrate levels suggest a concomitant upregulation of ketogenesis to ensure sufficient energy supply in the fasting state. Several differences in metabolomic profiles between Hispanic and non-Hispanic women demonstrate phenotypic variations in prenatal metabolism which should be considered in future studies.
Published:
2015-12
Title:
Metabolic profiles of male meat eaters, fish eaters, vegetarians, and vegans from the EPIC-Oxford cohort
Authors:
Schmidt, Julie A.; Rinaldi, Sabina; Ferrari, Pietro; Carayol, Marion; Achaintre, David; Scalbert, Augustin; Cross, Amanda J.; Gunter, Marc J.; Fensom, Georgina K.; Appleby, Paul N.; Key, Timothy J.; Travis, Ruth C.
Abstract:
CONCLUSIONS: Metabolic profiles in plasma could effectively differentiate between men from different habitual diet groups, especially vegan men compared with men who consume animal products. The difference in metabolic profiles was mainly explained by the lower concentrations of glycerophospholipids and sphingolipids in vegans.
Published:
2015-12
Title:
The influence of obesity on survival in early, high-risk breast cancer: results from the randomized SUCCESS A trial
Authors:
Widschwendter, Peter; Friedl, Thomas WP; Schwentner, Lukas; DeGregorio, Nikolaus; Jaeger, Bernadette; Schramm, Amelie; Bekes, Inga; Deniz, Miriam; Lato, Krisztian; Weissenbacher, Tobias; Kost, Bernd; Andergassen, Ulrich; Jueckstock, Julia; Neugebauer, Julia; Trapp, Elisabeth; Fasching, Peter A.; Beckmann, Matthias W.; Schneeweiss, Andreas; Schrader, Ines; Rack, Brigitte; Janni, Wolfgang; Scholz, Christoph
Abstract:
Introduction: Obese breast cancer patients have worse prognosis than normal weight patients, but the level at which obesity is prognostically unfavorable is unclear. Methods: This retrospective analysis was performed using data from the SUCCESS A trial, in which 3754 patients with high-risk early breast cancer were randomized to anthracycline- and taxane-based chemotherapy with or without gemcitabine. Patients were classified as underweight/normal weight (body mass index (BMI) < 25.0), overweight (BMI 25.0–29.9), slightly obese (BMI 30.0–34.9), moderately obese (BMI 35.0–39.9) and severely obese (BMI ≥ 40.0), and the effect of BMI on disease-free survival (DFS) and overall survival (OS) was evaluated (median follow-up 65 months). In addition, subgroup analyses were conducted to assess the effect of BMI in luminal A-like, luminal B-like, HER2 (human epidermal growth factor 2)-positive and triple-negative tumors. Results: Multivariate analyses revealed an independent prognostic effect of BMI on DFS (p = 0.001) and OS (p = 0.005). Compared with underweight/normal weight patients, severely obese patients had worse DFS (hazard ratio (HR) 2.70, 95 % confidence interval (CI) 1.71–4.28, p < 0.001) and OS (HR 2.79, 95 % CI 1.63–4.77, p
Published:
2015-12
Title:
White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease
Authors:
Klosinski, Lauren P.; Yao, Jia; Yin, Fei; Fonteh, Alfred N.; Harrington, Michael G.; Christensen, Trace A.; Trushina, Eugenia; Brinton, Roberta Diaz
Abstract:
White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical.
Published:
2015-12
Title:
[Starvation ketosis in a breastfeeding woman]
Authors:
Monnier, D.; Goulenok, T.; Allary, J.; Zarrouk, V.; Fantin, B.
Abstract:
INTRODUCTION: Bovine ketosis is a rare cause of metabolic acidosis. It is a starvation ketosis that appears in lactating woman. CASE REPORT: A 29-year-old woman had a previous gastric surgery one month ago while breastfeeding her 6-month child. She presented to emergency with dyspnea, fatigue, weight loss and anorexia. The explorations revealed a serious metabolic acidosis with a high anion gap, for which all other causes have been eliminated. CONCLUSION: A restrictive diet in lactating patients is a major risk of ketosis or bovine ketosis. Medico-surgical treatment of obesity during lactation seems unreasonable. Breastfeeding should be systematically sought before a medical and surgical management of obesity. With the spread of bariatric surgery, starvation ketosis is a cause of metabolic acidosis not to ignore.
Published:
2015-12
Title:
Evidence for effective interventions to reduce mental health-related stigma and discrimination in the medium and long term: Systematic review
Authors:
Mehta, N.; Clement, S.; Marcus, E.; Stona, A.-C.; Bezborodovs, N.; Evans-Lacko, S.; Palacios, J.; Docherty, M.; Barley, E.; Rose, D.; Koschorke, M.; Shidhaye, R.; Henderson, C.; Thornicroft, G.
Abstract:
Published:
2015-11
Title:
Herring and Beef Meals Lead to Differences in Plasma 2-Aminoadipic Acid, beta-Alanine, 4-Hydroxyproline, Cetoleic Acid, and Docosahexaenoic Acid Concentrations in Overweight Men
Authors:
Ross, Alastair B.; Svelander, Cecilia; Undeland, Ingrid; Pinto, Rui; Sandberg, Ann-Sofie
Abstract:
CONCLUSIONS: These results in overweight men confirm that DHA and cetoleic acid reflect herring intake, whereas beta-alanine and 4-hydroxyproline are potential biomarkers for beef intake. The greater postprandial rise in 2-aminoadipic acid after the beef meal, coupled to its proposed role in stimulating insulin secretion, may have importance in the context of red meat intake and increased diabetes risk. This trial was registered at clinicaltrials.gov as NCT02381613. Copyright © 2015 American Society for Nutrition.
Published:
2015-11
Title:
Ketosis may promote brain macroautophagy by activating Sirt1 and hypoxia-inducible factor-1
Authors:
McCarty, Mark F.; DiNicolantonio, James J.; O'Keefe, James H.
Abstract:
Ketogenic diets are markedly neuroprotective, but the basis of this effect is still poorly understood. Recent studies demonstrate that ketone bodies increase neuronal levels of hypoxia-inducible factor-1α (HIF-1α), possibly owing to succinate-mediated inhibition of prolyl hydroxylase activity. Moreover, there is reason to suspect that ketones can activate Sirt1 in neurons, in part by increasing cytoplasmic and nuclear levels of Sirt1's obligate cofactor NAD(+). Another recent study has observed reduced activity of mTORC1 in the hippocampus of rats fed a ketogenic diet - an effect plausibly attributable to Sirt1 activation. Increased activities of HIF-1 and Sirt1, and a decrease in mTORC1 activity, could be expected to collaborate in the induction of neuronal macroautophagy. Considerable evidence points to moderate up-regulation of neuronal autophagy as a rational strategy for prevention of neurodegenerative disorders; elimination of damaged mitochondria that overproduce superoxide, as well as clearance of protein aggregates that mediate neurodegeneration, presumably contribute to this protection. Hence, autophagy may mediate some of the neuroprotective benefits of ketogenic diets. Brain-permeable agents which activate AMP-activated kinase, such as metformin and berberine, as well as the Sirt1 activator nicotinamide riboside, can also boost neuronal autophagy, and may have potential for amplifying the impact of ketogenesis on this process. Since it might not be practical for most people to adhere to ketogenic diets continuously, alternative strategies are needed to harness the brain-protective potential of ketone bodies. These may include ingestion of medium-chain triglycerides or coconut oil, intermittent ketogenic dieting, and possibly the use of supplements that promote hepatic ketogenesis - notably carnitine and hydroxycitrate - in conjunction with dietary regimens characterized by long daily episodes of fasting or carbohydrate avoidance.
Published:
2015-11
Title:
Mitochondrial disorders: Disease mechanisms and therapeutic approaches
Authors:
Poole, Olivia V.; Hanna, Michael G.; Pitceathly, Robert D.S.
Abstract:
Mitochondrial disorders are now well recognized as an important cause of genetic disease. They exhibit remarkable phenotypic, biochemical, and molecular heterogeneity, and frequently involve multiple organ systems. Their complexity partly relates to the dual expression of mitochondrial proteins by both mitochondrial and nuclear genomic DNA. Multiple copies of mitochondrial DNA (mtDNA) are present in a single human mitochondrion. Each molecule exists as a double-stranded, circular, helical structure containing 37 genes: 13 encode polypeptide subunits, whilst the remaining 24 encode 22 transfer and 2 ribosomal RNAs necessary for their synthesis. These protein subunits contribute towards four of five multimeric enzymes (so-called complex I/III/IV/V, with complex II entirely nuclear-encoded) embedded in the inner mitochondrial membrane. The enzymes catalyze a sequence of redox reactions which ultimately generates adenine triphosphate, the cellular unit of energy, during oxidative phosphorylation (OXPHOS). The remaining OXPHOS subunits (more than 70 in total), in addition to the apparatus required for their transcription, translation, post-translational modification and assembly, are nuclear-encoded. The mitochondrion's dependence on nuclear DNA extends further to include the machinery required for the maintenance, replication, and repair of mtDNA molecules, the proteins for which are synthesized in the cell cytoplasm prior to transport across mitochondrial membrane for replication. Recent advancements in DNA analysis using next generation sequencing technology have provided an unprecedented expansion in the depth of knowledge concerning both molecular mechanisms and biological pathways which underpin many mitochondrial diseases. This understanding has led to the emergence of many potential targets and treatment strategies for these disorders for which there is currently no cure. This review highlights the challenges to therapy development and clinical trial design and outlines the approaches currently being investigated to treat this diverse group of disorders.
Published:
2015-11
Title:
Neurology of Nutritional Vitamin B12 Deficiency in Infants: Case Series From India and Literature Review
Authors:
Goraya, Jatinder Singh; Kaur, Sukhjot; Mehra, Bharat
Abstract:
We studied 27 infants aged 6 to 27 months with vitamin B12 deficiency also known as "infantile tremor syndrome" in India. All were exclusively breast-fed by vegetarian mothers. Developmental delay or regression, pallor, skin hyperpigmentation, and sparse brown hair were present in all. Majority were hypotonic and involuntary movements were encountered in 18. Anemia and macrocytosis was found in 83% and 71% infants, respectively. Low serum vitamin B12 was present in 12 of 21 infants. Seven of the 9 infants with normal serum vitamin B12 had received vitamin B12 before referral. Twelve mothers had low serum vitamin B12. Cerebral atrophy was present in all the 9 infants who underwent neuroimaging. Treatment with vitamin B12 resulted in dramatic improvement in general activity and appetite within 48 to 72 hours followed by return of lost milestones. Tremors resolved in all by 3 to 4 weeks. Nutritional vitamin B12 deficiency is a treatable cause of neurologic dysfunction in infants.
Published:
2015-11
Title:
Physical activity is just as good as CBT or drugs for depression
Authors:
Andersson, Eva; Hovland, Anders; Kjellman, Bengt; Taube, Jill; Martinsen, Egil
Abstract:
In this article on the effect of physical activity on depression, data have been drawn from several meta-analyses, in particular, the latest Cochrane review entitled »Exercise for depression« published in 2013. The results show that physical activity can help prevent the onset and relapse of depression. Depressed people should be recommended aerobic or muscular strength training. There is clear evidence that physical activity alone is beneficial for the treatment of mild and moderate depression and can reduce symptoms of mild to moderate depression to the same extent as standard treatments (psychotherapy and antidepressant medication). Combining physical activity with these treatments may yield additional benefits. Individuals with depression should be recommended physical activity in adjunct to psychotherapy and medication.
Published:
2015-11
Title:
Research gaps in evaluating the relationship of meat and health
Authors:
Klurfeld, David M.
Abstract:
Humans evolved as omnivores and it has been proposed that cooking meat allowed for evolution of larger brains that has led to our success as a species. Meat is one of the most nutrient dense foods, providing high-quality protein, heme iron, zinc, and vitamins B6 and B12. Despite these advantages, epidemiologic studies have linked consumption of red or processed meat with obesity, type 2 diabetes, cardiovascular diseases, and cancers of multiple organs. Most observational studies report small, increased relative risks. However, there are many limitations of such studies including inability to accurately estimate intake, lack of prespecified hypotheses, multiple comparisons, and confounding from many factors - including body weight, fruit/vegetable intake, physical activity, smoking, and alcohol - that correlate significantly either positively or negatively with meat intake and limit the reliability of conclusions from these studies. The observational studies are heterogeneous and do not fulfill many of the points proposed by AB Hill in 1965 for inferring causality; his most important factor was strength of the association which in dietary studies is usually
Published:
2015-11
Title:
A Randomized, Double-Blind, Placebo-Controlled Trial of Citicoline for Cocaine Dependence in Bipolar I Disorder
Authors:
Brown, E. Sherwood; Todd, Jackie Peterson; Hu, Lisa T.; Schmitz, Joy M.; Carmody, Thomas J.; Nakamura, Alyson; Sunderajan, Prabha; Rush, A. John; Adinoff, Bryon; Bret, Mary Ellen; Holmes, Traci; Lo, Alexander
Abstract:
Published:
2015-10
Title:
Association between sleep and working memory in children with ADHD: a cross-sectional study
Authors:
Sciberras, E.; DePetro, A.; Mensah, F.; Hiscock, H.
Abstract:
OBJECTIVE/BACKGROUND: This study aimed to examine the relationship between sleep problems and working memory in children aged 5-13 years with attention-deficit/hyperactivity disorder (ADHD). PATIENTS/METHODS: Children with ADHD were recruited into a randomized controlled trial from 21 paediatric practices in VIC, Australia. Cross-sectional data for intervention and control children were pooled at 6 months post randomization for the current analyses (n = 189). Children who met the Diagnostic Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for ADHD and had a parent-reported moderate/severe sleep problem that fulfilled diagnostic criteria for a behavioural sleep disorder were recruited into the study. Sleep was assessed by detailed parent (Children's Sleep Habits Questionnaire) and self-reports (Self-Sleep Report). Working memory was measured using the Working Memory Test Battery for Children (low and very low working memory defined as <25th and
Published:
2015-10
Title:
Cancers in Australia in 2010 attributable to overweight and obesity
Authors:
Kendall, Bradley J.; Wilson, Louise F.; Olsen, Catherine M.; Webb, Penelope M.; Neale, Rachel E.; Bain, Christopher J.; Whiteman, David C.
Abstract:
Objectives: To estimate the proportion and number of cancers occurring in Australia in 2010 attributable to overweight/obesity. Methods: We estimated the population attributable fraction (PAF) and number of cancers causally associated with overweight/obesity. We used standard formulae incorporating Australian prevalence data for body mass index (BMI), relative risks associated with BMI and cancer. We also estimated the proportion change in cancer incidence (potential impact fraction [PIF]) that may have occurred assuming that the prevalence of overweight/obesity had remained at 1990 levels. Results: An estimated 3,917 cancer cases (3.4% of all cancers) diagnosed in 2010 were attributable to overweight/obesity, including 1,101 colon cancers, 971 female post-menopausal breast cancers and 595 endometrial cancers (PAFs of 10%, 8% and 26%, respectively). Highest PAFs were observed for oesophageal adenocarcinoma (31%), endometrial cancer (26%) and kidney cancer (19%). If the prevalence of overweight/obesity in Australia had remained at levels prevailing in 1990, we estimate there would have been 820 fewer cancers diagnosed in 2010 (PIF 2%). Conclusions: Overweight/obesity causes a substantial number of cancers in Australia. Implications: Public health strategies to reduce the prevalence of overweight and obesity will reduce the incidence of cancer, particularly of the colon, breast and endometrium.
Published:
2015-10
Title:
Circulating profiling reveals the effect of a polyunsaturated fatty acid-enriched diet on common microRNAs
Authors:
Ortega, Francisco J.; Cardona-Alvarado, Mónica I.; Mercader, Josep M.; Moreno-Navarrete, José M.; Moreno, María; Sabater, Mònica; Fuentes-Batllevell, Núria; Ramírez-Chávez, Enrique; Ricart, Wifredo; Molina-Torres, Jorge; Pérez-Luque, Elva L.; Fernández-Real, José M.
Abstract:
BACKGROUND: Consumption of long-chain polyunsaturated fatty acids (PUFAs), which are abundant in seafood and nuts, ameliorates components of the metabolic syndrome. Circulating microRNAs (miRNAs) have demonstrated to be valuable biomarkers of metabolic diseases. Here, we investigated whether a sustained nuts-enriched diet can lead to changes in circulating miRNAs, in parallel to the dietary modification of fatty acids (FAs). METHODS AND RESULTS: The profile of 192 common miRNAs was assessed (TaqMan low-density arrays) in plasma from 10 healthy women before and after an 8-week trial with a normocaloric diet enriched with PUFAs (30 g/day of almonds and walnuts). The most relevant miRNAs were validated in an extended sample of 30 participants (8 men and 22 women). Adiponectin was measured by immunoassay and FAs by gas liquid chromatography coupled to mass spectrometry. The percentage of both ω-3 (P=.01) and ω-6 (P=.029) PUFAs of dietary origin (as inferred from plasma FA concentrations) increased, whereas saturated FAs decreased (P=.0008). Concomitantly with changes in circulating FAs, several miRNAs were modified by treatment, including decreased miR-328, miR-330-3p, miR-221 and miR-125a-5p, and increased miR-192, miR-486-5p, miR-19b, miR-106a, miR-769-5p, miR-130b and miR-18a. Interestingly, miR-106a variations in plasma correlated with changes in PUFAs, while miR-130b (r=0.58, P=.003) and miR-221 (r=0.46, P=.03) reflected changes in C-reactive protein. The dietary modulation of miR-125a-5p mirrored changes in fasting triglycerides (r=-0.44, P=.019) and increased adiponectin (r=0.43, P=.026). CONCLUSION: Dietary FAs (as inferred from plasma FA concentration) are linked to changes in circulating miRNAs, which may be modified by a PUFAs-enriched diet.
Published:
2015-10
Title:
Differences in micronucleus frequency and acrylamide adduct levels with hemoglobin between vegetarians and non-vegetarians
Authors:
Kotova, Natalia; Frostne, Cecilia; Abramsson-Zetterberg, Lilianne; Tareke, Eden; Bergman, Rolf; Haghdoost, Siamak; Paulsson, Birgit; Törnqvist, Margareta; Segerbäck, Dan; Jenssen, Dag; Grawé, Jan
Abstract:
Purpose: Nutrients and food constituents can prevent or contribute to genotoxicity. In this study, the possible influence of a vegetarian/non-vegetarian diet on genotoxic effects was investigated in 58 non-smoking healthy vegetarians (V) and non-vegetarians (NV), age 21-37 years from the Stockholm area in Sweden. Methods: Physical activity and dietary habits were similar in both groups, with the exception of the intake of meat and fish. Using flow cytometry, we determined the formation of micronuclei (MN) in transferrin-positive immature peripheral blood reticulocytes (Trf-Ret) (Total: n = 53; V: n = 27; NV: n = 26). Dietary exposure to acrylamide was measured through hemoglobin (Hb) adducts in peripheral erythrocytes (Total: n = 53; V: n = 29; NV: n = 24). Hb adducts of both acrylamide and its genotoxic metabolite glycidamide were monitored as a measure of the corresponding in vivo doses. Results: Our data demonstrated that compared with the non-vegetarians, the vegetarians exhibited lower frequencies of MN (fMN) in the Trf-Ret ( p < 0.01, Student's t test). A multivariate analysis demonstrated that there was no association between the fMN and factors such as age, sex, intake of vitamins/minerals, serum folic acid and vitamin B12 levels, physical activity, and body mass index. The mean Hb adduct levels of acrylamide and glycidamide showed no significant differences between vegetarians and non-vegetarians. Furthermore, there were no significant relationships between the adduct levels and fMN in the individuals. The ratio of the Hb adduct levels from glycidamide and acrylamide, however, showed a significant difference ( p
Published:
2015-10
Title:
Efficacy and safety of pregabalin in generalised anxiety disorder: A critical review of the literature
Authors:
Baldwin, David S; den Boer, Johan A; Lyndon, Gavin; Emir, Birol; Schweizer, Edward; Haswell, Hannah
Abstract:
The aim of this review is to summarise the literature on the efficacy and safety of pregabalin for the treatment of generalised anxiety disorder (GAD). Of 241 literature citations, 13 clinical trials were identified that were specifically designed to evaluate the efficacy and safety of pregabalin in GAD, including 11 randomised double-blind trials and two open-label studies. Pregabalin efficacy has been consistently demonstrated across the licensed dose range of 150–600 mg/day. Efficacy has been reported for pregabalin monotherapy in elderly patients with GAD, patients with severe anxiety, and for adjunctive therapy when added to a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor in patients who have failed to respond to an initial course of antidepressant therapy. The two most common adverse events with pregabalin are somnolence and dizziness, both of which appear to be dose-related. Pregabalin appears to have a low potential for causing withdrawal symptoms when long-term therapy is discontinued; however, tapering over the course of at least one week is recommended. A review of available evidence indicates that pregabalin is a well-tolerated and consistently effective treatment for GAD, with a unique mechanism of action that makes it a useful addition to the therapeutic armamentarium.
Published:
2015-10
Title:
GM-CSF: An Immune Modulatory Cytokine that can Suppress Autoimmunity
Authors:
Bhattacharya, Palash; Thiruppathi, Muthusamy; Elshabrawy, Hatem A.; Alharshawi, Khaled; Kumar, Prabhakaran; Prabhakar, Bellur S.
Abstract:
GM-CSF was originally identified as a colony stimulating factor (CSF) because of its ability to induce granulocyte and macrophage populations from precursor cells. Multiple studies have demonstrated that GM-CSF is also an immune-modulatory cytokine, capable of affecting not only the phenotype of myeloid lineage cells, but also T-cell activation through various myeloid intermediaries. This property has been implicated in the sustenance of several autoimmune diseases like arthritis and multiple sclerosis. In contrast, several studies using animal models have shown that GM-CSF is also capable of suppressing many autoimmune diseases like Crohn's disease, Type-1 diabetes, Myasthenia gravis and experimental autoimmune thyroiditis. Knockout mouse studies have suggested that the role of GM-CSF in maintaining granulocyte and macrophage populations in the physiological steady state is largely redundant. Instead, its immune-modulatory role plays a significant role in the development or resolution of autoimmune diseases. This is mediated either through the differentiation of precursor cells into specialized non-steady state granulocytes, macrophages and dendritic cells, or through the modulation of the phenotype of mature myeloid cells. Thus, outside of myelopoiesis, GM-CSF has a profound role in regulating the immune response and maintaining immunological tolerance.
Published:
2015-10
Title:
Hydration Status and Sodium Balance of Endurance Runners Consuming Postexercise Supplements of Varying Nutrient Content
Authors:
Pryor, J. Luke; Johnson, Evan C.; Del Favero, Jeffery; Monteleone, Andrew; Armstrong, Lawrence E.; Rodriguez, Nancy R.
Abstract:
Postexercise protein and sodium supplementation may aid recovery and rehydration. Preserved beef provides protein and contains high quantities of sodium that may alter performance related variables in runners. The purpose of this study was to determine the effects of consuming a commercial beef product postexercise on sodium and water balance. A secondary objective was to characterize effects of the supplementation protocols on hydration, blood pressure, body mass, and running economy. Eight trained males (age = 22 ± 3 y, VO2max = 66.4 ± 4.2 ml·kg-1·min-1) completed three identical weeks of run training (6 run·wk-1, 45 ± 6 min·run-1, 74 ± 5% HRR). After exercise, subjects consumed either, a beef nutritional supplement (beef jerky; [B]), a standard recovery drink (SRD), or SRD+B in a randomized counterbalanced design. Hydration status was assessed via urinary biomarkers and body mass. No main effects of treatment were observed for 24 hr urine volume (SRD, 1.7 ± 0.5; B, 1.8 ± 0.6; SRD+B, 1.4 ± 0.4 L·d-1), urine specific gravity (1.016 ± 0.005, 1.018 ± 0.006, 1.017 ± 0.006) or body mass (68.4 ± 8.2, 68.3 ± 7.7, 68.2 ± 8.1 kg). No main effect of treatment existed for sodium intake-loss (-713 ± 1486; -973 ± 1123; -980 ± 1220 mg·d-1). Mean arterial pressure (81.0 ± 4.6, 81.1 ± 7.3, 83.8 ± 5.4 mm Hg) and average exercise running economy (VO2: SRD, 47.9 ± 3.2; B, 47.2 ± 2.6; SRD+B, 46.2 ± 3.4 ml·kg-1·min-1) was not affected. Urinary sodium excretion accounted for the daily sodium intake due to the beef nutritional supplement. Findings suggest the commercial beef snack is a viable recovery supplement following endurance exercise without concern for hydration status, performance decrements, or cardiovascular consequences.
Published:
2015-10
Title:
Hypertonic Saline in Conjunction with High-Dose Furosemide Improves Dose–Response Curves in Worsening Refractory Congestive Heart Failure
Authors:
Paterna, Salvatore; Di Gaudio, Francesca; La Rocca, Vincenzo; Balistreri, Fabio; Greco, Massimiliano; Torres, Daniele; Lupo, Umberto; Rizzo, Giuseppina; di Pasquale, Pietro; Indelicato, Sergio; Cuttitta, Francesco; Butler, Javed; Parrinello, Gaspare
Abstract:
© 2015, Springer Healthcare. Introduction: Diuretic responsiveness in patients with chronic heart failure (CHF) is better assessed by urine production per unit diuretic dose than by the absolute urine output or diuretic dose. Diuretic resistance arises over time when the plateau rate of sodium and water excretion is reached prior to optimal fluid elimination and may be overcome when hypertonic saline solution (HSS) is added to high doses of furosemide. Methods: Forty-two consecutively hospitalized patients with refractory CHF were randomized in a 1:1:1 ratio to furosemide doses (125 mg, 250 mg, 500 mg) so that all patients received intravenous furosemide diluted in 150 ml of normal saline (0.9%) in the first step (0–24 h) and the same furosemide dose diluted in 150 ml of HSS (1.4%) in the next step (24–48 h) as to obtain 3 groups as follows: Fourteen patients receiving 125 mg (group 1), fourteen patients receiving 250 mg (group 2), and fourteen patients receiving 500 mg (group 3) of furosemide. Urine samples of all patients were collected at 30, 60, and 90 min, and 3, 4, 5, 6, 8, and 24 h after infusion. Diuresis, sodium excretion, osmolality, and furosemide concentration were evaluated for each urine sample. Results: After randomization, 40 patients completed the study. Two patients, one in group 2 and one in group 3 dropped out. Patients in group 1 (125 mg furosemide) had a mean age of 77 ± 17 years, 43% were male, 6 (43%) had heart failure with a preserved ejection fraction (HFpEF), and 64% were in New York Heart Association (NYHA) class IV; the mean age of patients in group 2 (250 mg furosemide) was 80 ± 8.1 years, 15% were male, 5 (38%) had HFpEF, and 84% were in NYHA class IV; and the mean age of patients in group 3 (500 mg furosemide) was 73 ± 12 years, 54% were male, 6 (46%) had HFpEF, and 69% were in NYHA class IV. HSS added to furosemide increased total urine output, sodium excretion, urinary osmolality, and furosemide urine delivery in all patients and at all time points. The percentage increase was 18,14, and 14% for urine output; 29, 24, and 16% for total sodium excretion; 45, 34, and 20% for urinary osmolarity; and 27, 36, and 32% for total furosemide excretion in groups 1, 2, and 3, respectively. These findings were translated in an improvement in the furosemide dose–response curves in these patients. Conclusion: These results may serve as new pathophysiological basis for HSS use in the treatment of refractory CHF.
Published:
2015-10
Title:
Intermittent fasting interventions for the treatment of overweight and obesity in adults aged 18 years and over: a systematic review protocol
Authors:
Jane, Louisa; Atkinson, Greg; Jaime, Victoria; Hamilton, Sharon; Waller, Gillian; Harrison, Samantha
Abstract:
REVIEW QUESTION/OBJECTIVE: Are intermittent fasting interventions an effective treatment for overweight and obesity in adults, when compared to usual care treatment (continuous daily energy restriction - reduced calorie diet) or no treatment (ad libitum diet)? BACKGROUND: Overweight and obesity (classified as Body Mass Index [BMI] of greater than or equal to 25 and 30 respectively) is a global public health concern, with more than 1.9 billion adults worldwide being overweight in 2014 (over 600 million of whom are obese), and resulting in more deaths than underweight. A raised BMI in adulthood is associated with an increased risk of developing a number of chronic diseases which include diabetes, cardiovascular disease, muscular skeletal disorders and some cancers. In addition to this substantial impact on individual health and well being, there are also significant wider costs, for example, in England the annual direct cost to the national health service for treating overweight, obesity and associated morbidity is estimated at over £5 billion pounds, with costs to the wider economy estimated at £27 billion. Therefore effective weight management is essential.As overweight and obesity results from an accumulation of excess body fat arising from an energy imbalance - consuming more energy (kcal) than is expended - the majority of weight management approaches center around behaviors to address this imbalance, i.e. reducing energy intake through caloric restriction and increasing energy expenditure through physical activity. However, the aetiology of overweight and obesity is highly complex, involving an interplay of biological, psychological, societal and environmental drivers. Consequently, effective weight management is challenging, and whilst there exists a plethora of available weight loss programs, not all are comprehensively evaluated and compared, and many weight loss attempts result in weight regain and poor long term results. It is therefore vitally important to review the effectiveness of all new approaches to support an evidence-based approach to weight management.Intermittent fasting (IF), also known as alternate day fasting (ADF), periodic fasting or intermittent energy restriction (IER) is a relatively new dietary approach to weight management that involves interspersing normal daily caloric intake with a short period of severe calorie restriction/fasting. In terms of the possible underlying biological benefits of intermittent fasting, there is some evidence, predominantly from animal studies, to demonstrate beneficial effects on weight loss and cardio-metabolic risk factors. Whilst the underpinning mechanistic evidence is limited, there is some evidence to suggest that the benefits may be explained mechanistically through fat utilization and nutritional stress. However current National Institute for Health and Care Excellence (NICE) guidance on the treatment of adult obesity does not recommend the routine use of very low calorie diets (VLCD) (defined as a hypocaloric diet of 800 or less kcal/day) for the treatment of adult obesity. The National Institute for Health and Care Excellence states that this approach should only be recommended if there is a clinical rationale for rapid weight loss and must be nutritionally complete, part of a multi-component weight management strategy, including ongoing support, and should be undertaken for a maximum of 12 weeks (followed continuously or intermittently). Furthermore, the British Dietetic Association raises concerns that rapid weight loss associated with fasting may largely be due to loss of water and glycogen rather than fat, and may result in fatigue, dizziness and low energy levels. Essentially IF involves the intermittent use of a VLCD, and there remain questions about the side effects of this approach, whether there is an optimal fasting pattern or calorie limit, and how sustainable it is for long term weight management.Intermittent fasting has recently gained much popularity following significant media attention. In the UK this dietary approach reached mainstream after a BBC Horizon documentary aired in August 2012, featured an IF approach called the 5:2 diet, which involves five days of regular eating patterns interchanged with two days of fasting (max 500kcal for women and 600kcal for men). However other IF patterns are used such as alternate day fasting. Despite the recent popularity of intermittent fasting and associated weight loss claims, the supporting evidence base in humans remains small and there is only one published systematic review examining the health benefits of this approach. However the aim of this review was to examine the impact of this intervention on wider health benefits (not specifically as a treatment approach for overweight and obesity), and did not provide a comprehensive methodology or meta-analysis of RCT data. This proposed review will hence address these gaps in the evidence base.
Published:
2015-10
Title:
Methylphenidate increases glucose uptake in the brain of young and adult rats
Authors:
Réus, Gislaine Z.; Scaini, Giselli; Titus, Stephanie E.; Furlanetto, Camila B.; Wessler, Leticia B.; Ferreira, Gabriela K.; Gonçalves, Cinara L.; Jeremias, Gabriela C.; Quevedo, João; Streck, Emilio L.
Abstract:
BACKGROUND: Methylphenidate (MPH) is the drug of choice for pharmacological treatment of attention deficit hyperactivity disorder. Studies have pointed to the role of glucose and lactate as well as in the action mechanisms of drugs used to treat these neuropsychiatric diseases. Thus, this study aims to evaluate the effects of MPH administration on lactate release and glucose uptake in the brains of young and adult rats. METHODS: MPH (1.0, 2.0 and 10.0mg/kg) or saline was injected in young and adult Wistar male rats either acutely (once) or chronically (once daily for 28 days). Then, the levels of lactate release and glucose uptake were assessed in the prefrontal cortex, hippocampus, striatum, cerebellum and cerebral cortex. RESULTS: Chronic MPH treatment increased glucose uptake at the dose of 10.0mg/kg in the prefrontal cortex and striatum, and at the dose of 2.0mg/kg in the cerebral cortex of young rats. In adult rats, an increase in glucose uptake was observed after acute administration of MPH at the dose of 10.0mg/kg in the prefrontal cortex. After chronic treatment, there was an increase in glucose uptake with MPH doses of 2.0 and 10.0mg/kg in the prefrontal cortex, and at an MPH dose of 2.0mg/kg in the striatum of adult rats. The lactate release did not change with either acute or chronic treatments in young or adult rats. CONCLUSIONS: These findings indicate that MPH increases glucose consumption in the brain, and that these changes are dependent on age and posology.
Published:
2015-10
Title:
Polyphenol metabolome in human urine and its association with intake of polyphenol-rich foods across European countries
Authors:
Edmands, William Mb; Ferrari, Pietro; Rothwell, Joseph A.; Rinaldi, Sabina; Slimani, Nadia; Barupal, Dinesh K.; Biessy, Carine; Jenab, Mazda; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Katzke, Verena A.; Kühn, Tilman; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Grioni, Sara; Tumino, Rosario; Vineis, Paolo; Mattiello, Amalia; Romieu, Isabelle; Scalbert, Augustin
Abstract:
BACKGROUND: An improved understanding of the contribution of the diet to health and disease risks requires accurate assessments of dietary exposure in nutritional epidemiologic studies. The use of dietary biomarkers may improve the accuracy of estimates. OBJECTIVE: We applied a metabolomic approach in a large cohort study to identify novel biomarkers of intake for a selection of polyphenol-containing foods. The large chemical diversity of polyphenols and their wide distribution over many foods make them ideal biomarker candidates for such foods. DESIGN: Metabolic profiles were measured with the use of high-resolution mass spectrometry in 24-h urine samples from 481 subjects from the large European Prospective Investigation on Cancer and Nutrition cohort. Peak intensities were correlated to acute and habitual dietary intakes of 6 polyphenol-rich foods (coffee, tea, red wine, citrus fruit, apples and pears, and chocolate products) measured with the use of 24-h dietary recalls and food-frequency questionnaires, respectively. RESULTS: Correlation (r > 0.3, P 0.3, VIP > 1.5] analyses showed that >2000 mass spectral features from urine metabolic profiles were significantly associated with the consumption of the 6 selected foods. More than 80 polyphenol metabolites associated with the consumption of the selected foods could be identified, and large differences in their concentrations reflecting individual food intakes were observed within and between 4 European countries. Receiver operating characteristic curves showed that 5 polyphenol metabolites, which are characteristic of 5 of the 6 selected foods, had a high predicting ability of food intake. CONCLUSION: Highly diverse food-derived metabolites (the so-called food metabolome) can be characterized in human biospecimens through this powerful metabolomic approach and screened to identify novel biomarkers for dietary exposures, which are ultimately essential to better understand the role of the diet in the cause of chronic diseases.
Published:
2015-10
Title:
Post-illumination pupil response after blue light: Reliability of optimized melanopsin-based phototransduction assessment
Authors:
van der Meijden, Wisse P.; te Lindert, Bart H. W.; Bijlenga, Denise; Coppens, Joris E.; Gómez-Herrero, Germán; Bruijel, Jessica; Kooij, J. J. Sandra; Cajochen, Christian; Bourgin, Patrice; Van Someren, Eus J. W.
Abstract:
Melanopsin-containing retinal ganglion cells have recently been shown highly relevant to the non-image forming effects of light, through their direct projections on brain circuits that regulate alertness, mood and circadian rhythms. A quantitative assessment of functionality of the melanopsin-signaling pathway could be highly relevant in order to mechanistically understand individual differences in the effects of light on these regulatory systems. We here propose and validate a reliable quantification of the melanopsin-dependent Post-Illumination Pupil Response (PIPR) after blue light, and evaluated its sensitivity to dark adaptation, time of day, body posture, and light exposure history. Pupil diameter of the left eye was continuously measured during a series of light exposures to the right eye, of which the pupil was dilated using tropicamide 0.5%. The light exposure paradigm consisted of the following five consecutive blocks of five minutes: baseline dark; monochromatic red light (peak wavelength: 630 nm, luminance: 375 cd/m(2)) to maximize the effect of subsequent blue light; dark; monochromatic blue light (peak wavelength: 470 nm, luminance: 375 cd/m(2)); and post-blue dark. PIPR was quantified as the difference between baseline dark pupil diameter and post-blue dark pupil diameter (PIPR-mm). In addition, a relative PIPR was calculated by dividing PIPR by baseline pupil diameter (PIPR-%). In total 54 PIPR assessments were obtained in 25 healthy young adults (10 males, mean age ± SD: 26.9 ± 4.0 yr). From repeated measurements on two consecutive days in 15 of the 25 participants (6 males, mean age ± SD: 27.8 ± 4.3 yrs) test-retest reliability of both PIPR outcome parameters was calculated. In the presence of considerable between-subject differences, both outcome parameters had very high test-retest reliability: Cronbach's α > 0.90 and Intraclass Correlation Coefficient > 0.85. In 12 of the 25 participants (6 males, mean age ± SD: 26.5 ± 3.6 yr) we examined the potential confounding effects of dark adaptation, time of the day (morning vs. afternoon), body posture (upright vs. supine position), and 24-h environmental light history on the PIPR assessment. Mixed effect regression models were used to analyze these possible confounders. A supine position caused larger PIPR-mm (β = 0.29 mm, SE = 0.10, p = 0.01) and PIPR-% (β = 4.34%, SE = 1.69, p = 0.02), which was due to an increase in baseline dark pupil diameter; this finding is of relevance for studies requiring a supine posture, as in functional Magnetic Resonance Imaging, constant routine protocols, and bed-ridden patients. There were no effects of dark adaptation, time of day, and light history. In conclusion, the presented method provides a reliable and robust assessment of the PIPR to allow for studies on individual differences in melanopsin-based phototransduction and effects of interventions.
Published:
2015-10
Title:
Skeptical of medical science reports?
Authors:
Gyles, Carlton
Abstract:
Published:
2015-10
Title:
The mitochondrial voltage-dependent anion channel 1 in tumor cells
Authors:
Shoshan-Barmatz, Varda; Ben-Hail, Danya; Admoni, Lee; Krelin, Yakov; Tripathi, Shambhoo Sharan
Abstract:
VDAC1 is found at the crossroads of metabolic and survival pathways. VDAC1 controls metabolic cross-talk between mitochondria and the rest of the cell by allowing the influx and efflux of metabolites, ions, nucleotides, Ca2+ and more. The location of VDAC1 at the outer mitochondrial membrane also enables its interaction with proteins that mediate and regulate the integration of mitochondrial functions with cellular activities. As a transporter of metabolites, VDAC1 contributes to the metabolic phenotype of cancer cells. Indeed, this protein is over-expressed in many cancer types, and silencing of VDAC1 expression induces an inhibition of tumor development. At the same time, along with regulating cellular energy production and metabolism, VDAC1 is involved in the process of mitochondria-mediated apoptosis by mediating the release of apoptotic proteins and interacting with anti-apoptotic proteins. The engagement of VDAC1 in the release of apoptotic proteins located in the inter-membranal space involves VDAC1 oligomerization that mediates the release of cytochrome c and AIF to the cytosol, subsequently leading to apoptotic cell death. Apoptosis can also be regulated by VDAC1, serving as an anchor point for mitochondria-interacting proteins, such as hexokinase (HK), Bcl2 and Bcl-xL, some of which are also highly expressed in many cancers. By binding to VDAC1, HK provides both a metabolic benefit and apoptosis-suppressive capacity that offer the cell a proliferative advantage and increase its resistance to chemotherapy. Thus, these and other functions point to VDAC1 as an excellent target for impairing the re-programed metabolism of cancer cells and their ability to evade apoptosis. Here, we review current evidence pointing to the function of VDAC1 in cell life and death, and highlight these functions in relation to both cancer development and therapy. In addressing the recently solved 3D structures of VDAC1, this review will point to structure-function relationships of VDAC as critical for deciphering how this channel can perform such a variety of roles, all of which are important for cell life and death. Finally, this review will also provide insight into VDAC function in Ca2+ homeostasis, protection against oxidative stress, regulation of apoptosis and involvement in several diseases, as well as its role in the action of different drugs. We will discuss the use of VDAC1-based strategies to attack the altered metabolism and apoptosis of cancer cells. These strategies include specific siRNA able to impair energy and metabolic homeostasis, leading to arrested cancer cell growth and tumor development, as well VDAC1-based peptides that interact with anti-apoptotic proteins to induce apoptosis, thereby overcoming the resistance of cancer cell to chemotherapy. Finally, small molecules targeting VDAC1 can induce apoptosis. VDAC1 can thus be considered as standing at the crossroads between mitochondrial metabolite transport and apoptosis and hence represents an emerging cancer drug target. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.
Published:
2015-10
Title:
Ascendancy of the Tudulgal, central Torres Strait: Socio-political manipulation and domination of an archipelago polity
Authors:
McNiven, Ian J.
Abstract:
Survival for the ethnographically-known Kulkalgal of the drought-prone reef islands of central Torres Strait focused on high mobility, translocation, food storage, and importation of cultivated plant foods. These buffering mechanisms were underpinned by a dynamic and flexible web of social alliances and exchange relationships spread across 700 km of seaspace. The small and resource-poor island of Tudu (inhabited by the Tudulgal, a subgroup of the Kulkalgal) was a central place within the regional archipelago polity. It is hypothesised that the Tudulgal strategically increased resource self-sufficiency and orchestrated socio-political dominance to help obviate economic vulnerability. These ethnographic patterns provide the basis for developing archaeological hypotheses on socio-political ascendancy of the Tudulgal, focusing on chronological insights into material dimensions of increasing self-sufficiency (e.g., intensified use of local marine foods, horticultural garden produce, and clam shell technology), and increasing regional domination of exchange (e.g., intensified importation of exotics), canoe trade (e.g., intensified production of shell valuables), and headhunting cults and warfare (e.g., intensified use of skull shrines). While cultural complexity is usually associated with resource-rich coastal contexts and hierarchical societies, the Tudulgal demonstrate that regional polity development and associated socio-political and socio-economic complexity can occur in response to limited availability of critical terrestrial food and water resources in societies that are largely heterarchical and egalitarian.
Published:
2015-09
Title:
Bidirectional Association Between Depression and Fibromyalgia Syndrome: A Nationwide Longitudinal Study
Authors:
Chang, Meng-Han; Hsu, Ju-Wei; Huang, Kai-Lin; Su, Tung-Ping; Bai, Ya-Mei; Li, Cheng-Ta; Yang, Albert C.; Chang, Wen-Han; Chen, Tzeng-Ji; Tsai, Shih-Jen; Chen, Mu-Hong
Abstract:
Several cross-sectional studies have reported a common comorbidity between depression and fibromyalgia syndrome (FMS). However, a bidirectional temporal association between these 2 distinct diseases has rarely been investigated. Using the Taiwan National Health Insurance Research Database, 25,969 patients with FMS and without any psychiatric disorder and 17,142 patients with depression and without FMS between 2000 and 2008 were enrolled and separately compared with age- and sex-matched (1:4) control groups. Patients with FMS who developed a new-onset depression and those with depression who developed new-onset FMS were identified during follow-up (to the end of 2011). The conditional Cox regression analyses, after adjustment for demographic data and medical comorbidities, showed that the patients with FMS were associated with an increased risk (hazard ratio [HR] 7.46, 95% confidence interval [CI] 6.77–8.22) of subsequent depression and that those with depression were associated with an increased risk (HR 6.28, 95% CI 5.67–6.96) of subsequent FMS. Our results supported a bidirectional temporal association between depression and FMS. Each disease occurring first may increase the risk of the other subsequently. Further study may be necessary to determine the underlying mechanism between depression and FMS and to clarify whether a prompt intervention for depression or FMS may decrease the risk of the other later in life.
Published:
2015-09
Title:
Diagnosis and management of mitochondrial disease: A consensus statement from the Mitochondrial Medicine Society
Authors:
Parikh, Sumit; Goldstein, Amy; Koenig, Mary Kay; Scaglia, Fernando; Enns, Gregory M.; Saneto, Russell; Anselm, Irina; Cohen, Bruce H.; Falk, Marni J.; Greene, Carol; Gropman, Andrea L.; Haas, Richard; Hirano, Michio; Morgan, Phil; Sims, Katherine; Tarnopolsky, Mark; Van Hove, Johan L.K.; Wolfe, Lynne; DiMauro, Salvatore
Abstract:
Purpose: The purpose of this statement is to review the literature regarding mitochondrial disease and to provide recommendations for optimal diagnosis and treatment. This statement is intended for physicians who are engaged in diagnosing and treating these patients. Methods: The Writing Group members were appointed by the Mitochondrial Medicine Society. The panel included members with expertise in several different areas. The panel members utilized a comprehensive review of the literature, surveys, and the Delphi method to reach consensus. We anticipate that this statement will need to be updated as the field continues to evolve. Results: Consensus-based recommendations are provided for the diagnosis and treatment of mitochondrial disease. Conclusion: The Delphi process enabled the formation of consensus-based recommendations. We hope that these recommendations will help standardize the evaluation, diagnosis, and care of patients with suspected or demonstrated mitochondrial disease.
Published:
2015-09
Title:
Diets with high-fat cheese, high-fat meat, or carbohydrate on cardiovascular risk markers in overweight postmenopausal women: a randomized crossover trial
Authors:
Thorning, Tanja K.; Raziani, Farinaz; Bendsen, Nathalie T.; Astrup, Arne; Tholstrup, Tine; Raben, Anne
Abstract:
CONCLUSIONS: Diets with cheese and meat as primary sources of SFAs cause higher HDL cholesterol and apo A-I and, therefore, appear to be less atherogenic than is a low-fat, high-carbohydrate diet. Also, our findings confirm that cheese increases fecal fat excretion. This trial was registered at clinicaltrials.gov as NCT01739153. Copyright © 2015 American Society for Nutrition.
Published:
2015-09
Title:
Effect of different fat-enriched meats on non-cholesterol sterols and oxysterols as markers of cholesterol metabolism: Results of a randomized and cross-over clinical trial
Authors:
Baila-Rueda, L.; Mateo-Gallego, R.; Perez-Calahorra, S.; Lamiquiz-Moneo, I.; de Castro-Oros, I.; Cenarro, A.; Civeira, F.
Abstract:
REGISTRATION NUMBER FOR CLINICAL TRIALS: ClinicalTrials.gov PRS, NCT02259153. Copyright © 2015 Elsevier B.V. All rights reserved.
Published:
2015-09
Title:
Family interventions to improve diabetes outcomes for adults
Authors:
Baig, Arshiya A.; Benitez, Amanda; Quinn, Michael T.; Burnet, Deborah L.
Abstract:
Diabetes self-care is a critical aspect of disease management for adults with diabetes. Since family members can play a vital role in a patient’s disease management, involving them in self-care interventions may positively influence patients’ diabetes outcomes. We systematically reviewed family-based interventions for adults with diabetes published from 1994 to 2014 and assessed their impact on patients’ diabetes outcomes and the extent of family involvement. We found 26 studies describing family-based diabetes interventions for adults. Interventions were conducted across a range of patient populations and settings. The degree of family involvement varied across studies. We found evidence for improvement in patients’ self-efficacy, perceived social support, diabetes knowledge, and diabetes self-care across the studies. Owing to the heterogeneity of the study designs, types of interventions, reporting of outcomes, and family involvement, it is difficult to determine how family participation in diabetes interventions may affect patients’ clinical outcomes. Future studies should clearly describe the role of family in the intervention, assess quality and extent of family participation, and compare patient outcomes with and without family involvement.
Published:
2015-09
Title:
Glycemic modulation in neuro-oncology: experience and future directions using a modified Atkins diet for high-grade brain tumors
Authors:
Strowd, Roy E.; Cervenka, Mackenzie C.; Henry, Bobbie J.; Kossoff, Eric H.; Hartman, Adam L.; Blakeley, Jaishri O.
Abstract:
Dietary glycemic modulation through high-fat, low-carbohydrate diets, which induce a state of systemic ketosis and alter systemic metabolic signaling, have been incorporated into the clinical management of patients with neurological disease for more than a century. Mounting preclinical evidence supports the antitumor, proapoptotic, and antiangiogenic effects of disrupting glycolytic metabolism through dietary intervention. In recent years, interest in incorporating such novel therapeutic strategies in neuro-oncology has increased. To date, 3 published studies incorporating novel dietary therapies in oncology have been reported, including one phase I study in neuro-oncology, and have set the stage for further study in this field. In this article, we review the biochemical pathways, preclinical data, and early clinical translation of dietary interventions that modulate systemic glycolytic metabolism in the management of primary malignant brain tumors. We introduce the modified Atkins diet (MAD), a novel dietary alternative to the classic ketogenic diet, and discuss the critical issues facing future study.
Published:
2015-09
Title:
Homozygous mutations in MFN2 cause multiple symmetric lipomatosis associated with neuropathy
Authors:
Sawyer, Sarah L.; Ng, Andy Cheuk Him; Micheil Innes, A.; Wagner, Justin D.; Dyment, David A.; Tetreault, Martine; Majewski, Jacek; Boycott, Kym M.; Screaton, Robert A.; Nicholson, Garth; MacKenzie, Alex; Brudno, Michael; Bulman, Dennis
Abstract:
Multiple symmetric lipomatosis (MSL) is a mitochondrial disorder with impaired brown fat metabolism that has been associated with MERRF mutations in some, but not all, patients. We studied a sibling pair and an unrelated indiviadual who presented with MSL and neuropathy to determine the genetic etiology of this disorder in patients who did not carry the MSL-associated MERRF mutation. Whole-exome sequencing was performed on the siblings, and a rare, shared homozygous mutation in MFN2 (c.2119C\textgreaterT: p. R707W) was identified. The mutation was not present in their healthy siblings. In silico programs predict it to be pathogenic, and heterozygous carriers of the MFN2 p. R707W substitution are known to have Charcot-Marie-Tooth (CMT) disease. A third, unrelated patient with multiple symmetrical lipomatosis and neuropathy also harbored the same homozygous mutation and had been previously diagnosed with CMT. Functional studies in patient fibroblasts demonstrate that the p. R707W substitution impairs homotypic (MFN2-MFN2) protein interactions required for normal activity and renders mitochondria prone to perinuclear aggregation. These findings show that homozygous mutations at p. R707W in MFN2 are a novel cause of multiple symmetrical lipomatosis.
Published:
2015-09
Title:
Incorporation of eicosapentaenioic and docosahexaenoic acids into breast adipose tissue of women at high risk of breast cancer: a randomized clinical trial of dietary fish and n-3 fatty acid capsules
Authors:
Straka, Shana; Lester, Joanne L.; Cole, Rachel M.; Andridge, Rebecca R.; Puchala, Sarah; Rose, Angela M.; Clinton, Steven K.; Belury, Martha A.; Yee, Lisa D.
Abstract:
SCOPE: The fatty acid profile of dietary lipids is reflected in mammary adipose tissue and may influence mammary gland biology and cancer risk. To determine the effects of fish consumption on breast adipose tissue fatty acids, we conducted a study of fish versus n-3 PUFA supplements in women at increased risk of breast cancer. METHODS AND RESULTS: High risk women were randomized to comparable doses of marine n-3 PUFAs as canned salmon + albacore or capsules for 3 months. Pre- and posttreatment fatty acid profiles were obtained by GC. Dietary fish (n = 12) and n-3 PUFA capsules (n = 13) yielded increased eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in plasma (p < 0.0001), erythrocyte membranes (p < 0.0001), and breast fat (p
Published:
2015-09
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