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Title:
Biomarkers of Nutrition for Development (BOND)-Zinc Review
Authors:
King, Janet C.; Brown, Kenneth H.; Gibson, Rosalind S.; Krebs, Nancy F.; Lowe, Nicola M.; Siekmann, Jonathan H.; Raiten, Daniel J.
Abstract:
Zinc is required for multiple metabolic processes as a structural, regulatory, or catalytic ion. Cellular, tissue, and whole-body zinc homeostasis is tightly controlled to sustain metabolic functions over a wide range of zinc intakes, making it difficult to assess zinc insufficiency or excess. The BOND (Biomarkers of Nutrition for Development) Zinc Expert Panel recommends 3 measurements for estimating zinc status: dietary zinc intake, plasma zinc concentration (PZC), and height-for-age of growing infants and children. The amount of dietary zinc potentially available for absorption, which requires an estimate of dietary zinc and phytate, can be used to identify individuals and populations at risk of zinc deficiency. PZCs respond to severe dietary zinc restriction and to zinc supplementation; they also change with shifts in whole-body zinc balance and clinical signs of zinc deficiency. PZC cutoffs are available to identify individuals and populations at risk of zinc deficiency. However, there are limitations in using the PZC to assess zinc status. PZCs respond less to additional zinc provided in food than to a supplement administered between meals, there is considerable interindividual variability in PZCs with changes in dietary zinc, and PZCs are influenced by recent meal consumption, the time of day, inflammation, and certain drugs and hormones. Insufficient data are available on hair, urinary, nail, and blood cell zinc responses to changes in dietary zinc to recommend these biomarkers for assessing zinc status. Of the potential functional indicators of zinc, growth is the only one that is recommended. Because pharmacologic zinc doses are unlikely to enhance growth, a growth response to supplemental zinc is interpreted as indicating pre-existing zinc deficiency. Other functional indicators reviewed but not recommended for assessing zinc nutrition in clinical or field settings because of insufficient information are the activity or amounts of zinc-dependent enzymes and proteins and biomarkers of oxidative stress, inflammation, or DNA damage.
Published:
March 8, 2016
Title:
Ultra-processed foods and added sugars in the US diet: evidence from a nationally representative cross-sectional study
Authors:
Martínez Steele, Eurídice; Baraldi, Larissa Galastri; Louzada, Maria Laura da Costa; Moubarac, Jean-Claude; Mozaffarian, Dariush; Monteiro, Carlos Augusto
Abstract:
OBJECTIVES: To investigate the contribution of ultra-processed foods to the intake of added sugars in the USA. Ultra-processed foods were defined as industrial formulations which, besides salt, sugar, oils and fats, include substances not used in culinary preparations, in particular additives used to imitate sensorial qualities of minimally processed foods and their culinary preparations. DESIGN: Cross-sectional study. SETTING: National Health and Nutrition Examination Survey 2009-2010. PARTICIPANTS: We evaluated 9317 participants aged 1+ years with at least one 24 h dietary recall. MAIN OUTCOME MEASURES: Average dietary content of added sugars and proportion of individuals consuming more than 10% of total energy from added sugars. DATA ANALYSIS: Gaussian and Poisson regressions estimated the association between consumption of ultra-processed foods and intake of added sugars. All models incorporated survey sample weights and adjusted for age, sex, race/ethnicity, family income and educational attainment. RESULTS: Ultra-processed foods comprised 57.9% of energy intake, and contributed 89.7% of the energy intake from added sugars. The content of added sugars in ultra-processed foods (21.1% of calories) was eightfold higher than in processed foods (2.4%) and fivefold higher than in unprocessed or minimally processed foods and processed culinary ingredients grouped together (3.7%). Both in unadjusted and adjusted models, each increase of 5 percentage points in proportional energy intake from ultra-processed foods increased the proportional energy intake from added sugars by 1 percentage point. Consumption of added sugars increased linearly across quintiles of ultra-processed food consumption: from 7.5% of total energy in the lowest quintile to 19.5% in the highest. A total of 82.1% of Americans in the highest quintile exceeded the recommended limit of 10% energy from added sugars, compared with 26.4% in the lowest. CONCLUSIONS: Decreasing the consumption of ultra-processed foods could be an effective way of reducing the excessive intake of added sugars in the USA.
Published:
March 8, 2016
Title:
Are more diverse parts of the mammalian skull more labile?
Authors:
Linde-Medina, Marta; Boughner, Julia; Santana, Sharlene; Diogo, Rui
Abstract:
Morphological variation is unevenly distributed within the mammalian skull; some of its parts have diversified more than others. It is commonly thought that this pattern of variation is mainly the result of the structural organization of the skull, as defined by the pattern and magnitude of trait covariation. Patterns of trait covariation can facilitate morphological diversification if they are aligned in the direction of selection, or these patterns can constrain diversification if oriented in a different direction. Within this theoretical framework, it is thought that more variable parts possess patterns of trait covariation that made them more capable of evolutionary change, that is, are more labile. However, differences in the degree of morphological variation among skull traits could arise despite variation in trait lability if, for example, some traits have evolved at a different rate and/or undergone stabilizing selection. Here, we test these hypotheses in the mammalian skull using 2D geometric morphometrics to quantify skull shape and estimating constraint, rates of evolution, and lability. Contrary to the expectations, more variable parts of the skull across mammalian species are less capable of evolutionary change than are less variable skull parts. Our results suggest that patterns of morphological variation in the skull could result from differences in rate of evolution and stabilizing selection.
Published:
March 3, 2016
Title:
An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity
Authors:
Simopoulos, Artemis P.
Abstract:
In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity.
Published:
March 1, 2016
Title:
Antidepressant-Induced Hyponatremia in Older Adults
Authors:
Viramontes, Terry S.; Truong, Havan; Linnebur, Sunny A.
Abstract:
OBJECTIVE: To describe the prevalence of hyponatremia in older adults related to antidepressive agents and identify potential alternative options in older adults with a lowbaseline serum sodium concentration and/or when a patient has experienced hyponatremia as a result of taking an antidepressant. DATA SOURCES: A PubMed search was conducted on November 10, 2015. Search terms included: antidepressive agents, antidepressive agents second-generation, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, hyponatremia, milnacipran, mirtazapine, paroxetine, reboxetine, syndrome of inappropriate antidiuretic hormone, sertraline, trazodone, venlafaxine, and vilazodone. Filters included English language. A search of product labeling was also conducted. STUDY SELECTION: Out of 363 results, 124 publications were identified and reviewed along with 11 additional references. Publications were chosen based on relevance to the review: case reports of patients 60 years of age or older or clinical investigations of the association between hyponatremia and antidepressants in older adults. DATA EXTRACTION: Hyponatremia was counted as an adverse effect if an antidepressant was the likely cause of hyponatremia, and hyponatremia was resolved after withdrawal. DATA SYNTHESIS: Antidepressant-induced hyponatremia in older adults is fairly common. Selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, and mirtazapine were implicated in the majority of the case reports and clinical studies evaluating older adults. Bupropion, trazodone, and tricyclic antidepressants were implicated less often in the same literature. CONCLUSION: Given its unique mechanism of action, bupropion may be the most appropriate antidepressant for older adults at risk for antidepressant-induced hyponatremia.
Published:
February 29, 2016
Title:
Brain size predicts problem-solving ability in mammalian carnivores
Authors:
Benson-Amram, Sarah; Dantzer, Ben; Stricker, Gregory; Swanson, Eli M.; Holekamp, Kay E.
Abstract:
Intelligence presents evolutionary biology with one of its greatest challenges. It has long been thought that species with relatively large brains for their body size are more intelligent. However, despite decades of research, the idea that brain size ...
Published:
February 29, 2016
Title:
Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia: A Network Meta-analysis
Authors:
Samara, Myrto T.; Dold, Markus; Gianatsi, Myrsini; Nikolakopoulou, Adriani; Helfer, Bartosz; Salanti, Georgia; Leucht, Stefan
Abstract:
OBJECTIVE To integrate all the randomized evidence from the available antipsychotics used for treatment-resistant schizophrenia by performing a network meta-analysis. DATA SOURCES MEDLINE, EMBASE, Biosis, PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, World Health Organization International Trial Registry, and clinicaltrials.gov were searched up to June 30, 2014. STUDY SELECTION At least 2 independent reviewers selected published and unpublished single- and double-blind RCTs in treatment-resistant schizophrenia (any study-defined criterion) that compared any antipsychotic (at any dose and in any form of administration) with another antipsychotic or placebo. DATA EXTRACTION AND SYNTHESIS At least 2 independent reviewers extracted all data into standard forms and assessed the quality of all included trials with the Cochrane Collaboration’s risk-of-bias tool. Data were pooled using a random-effects model in a Bayesian setting. MAIN OUTCOMES AND MEASURES The primary outcome was efficacy as measured by overall change in symptoms of schizophrenia. Secondary outcomes included change in positive and negative symptoms of schizophrenia, categorical response to treatment, dropouts for any reason and for inefficacy of treatment, and important adverse events. RESULTS Forty blinded RCTs with 5172 unique participants (71.5% men; mean [SD] age, 38.8 [3.7] years) were included in the analysis. Few significant differences were found in all outcomes. In the primary outcome (reported as standardized mean difference; 95% credible interval), olanzapine was more effective than quetiapine (−0.29; −0.56 to −0.02), haloperidol (−0. 29; −0.44 to −0.13), and sertindole (−0.46; −0.80 to −0.06); clozapine was more effective than haloperidol (−0.22; −0.38 to −0.07) and sertindole (−0.40; −0.74 to −0.04); and risperidone was more effective than sertindole (−0.32; −0.63 to −0.01). A pattern of superiority for olanzapine, clozapine, and risperidone was seen in other efficacy outcomes, but results were not consistent and effect sizes were usually small. In addition, relatively few RCTs were available for antipsychotics other than clozapine, haloperidol, olanzapine, and risperidone. The most surprising finding was that clozapine was not significantly better than most other drugs. CONCLUSIONS AND RELEVANCE Insufficient evidence exists on which antipsychotic is more efficacious for patients with treatment-resistant schizophrenia, and blinded RCTs—in contrast to unblinded, randomized effectiveness studies—provide little evidence of the superiority of clozapine compared with other second-generation antipsychotics. Future clozapine studies with high doses and patients with extremely treatment-refractory schizophrenia might be most promising to change the current evidence.
Published:
February 29, 2016
Title:
Neandertals' large lower thorax may represent adaptation to high protein diet
Authors:
Ben-Dor, Miki; Gopher, Avi; Barkai, Ran
Abstract:
Humans are limited in their capacity to convert protein into energy. We present a hypothesis that a “bell” shaped thorax and a wide pelvis evolved in Neandertals, at least in part, as an adaptation to a high protein diet. A high protein diet created a need to house an enlarged liver and urinary system in a wider lower trunk. To test the hypothesis, we applied a model developed to identify points of nutritional stress. A ratio of obligatory dietary fat to total animal fat and protein sourced calories is calculated based on various known and estimated parameters. Stress is identified when the obligatory dietary fat ratio is higher than fat content ratios in available prey. The model predicts that during glacial winters, when carbohydrates weren't available, 74%−85% of Neandertals' caloric intake would have had to come from animal fat. Large animals contain around 50% fat calories, and their fat content is diminished during winter, so a significant stressful dietary fat deficit was identified by the model. This deficit could potentially be ameliorated by an increased capability to convert protein into energy. Given that high protein consumption is associated with larger liver and kidneys in animal models, it appears likely that the enlarged inferior section of the Neandertals thorax and possibly, in part, also his wide pelvis, represented an adaptation to provide encasement for those enlarged organs. Behavioral and evolutionary implications of the hypothesis are also discussed. Am J Phys Anthropol, 2016.
Published:
February 29, 2016
Title:
IκBα mediates prostate cancer cell death induced by combinatorial targeting of the androgen receptor
Authors:
Carter, Sarah Louise; Centenera, Margaret Mary; Tilley, Wayne Desmond; Selth, Luke Ashton; Butler, Lisa Maree
Abstract:
Background Combining different clinical agents to target multiple pathways in prostate cancer cells, including androgen receptor (AR) signaling, is potentially an effective strategy to improve outcomes for men with metastatic disease. We have previously demonstrated that sub-effective concentrations of an AR antagonist, bicalutamide, and the histone deacetylase inhibitor, vorinostat, act synergistically when combined to cause death of AR-dependent prostate cancer cells. Methods In this study, expression profiling of human prostate cancer cells treated with bicalutamide or vorinostat, alone or in combination, was employed to determine the molecular mechanisms underlying this synergistic action. Cell viability assays and quantitative real time PCR were used to validate identified candidate genes. Results A substantial proportion of the genes modulated by the combination of bicalutamide and vorinostat were androgen regulated. Independent pathway analysis identified further pathways and genes, most notably NFKBIA (encoding IκBα, an inhibitor of NF-κB and p53 signaling), as targets of this combinatorial treatment. Depletion of IκBα by siRNA knockdown enhanced apoptosis of prostate cancer cells, while ectopic overexpression of IκBα markedly suppressed cell death induced by the combination of bicalutamide and vorinostat. Conclusion These findings implicate IκBα as a key mediator of the apoptotic action of this combinatorial AR targeting strategy and a promising new therapeutic target for prostate cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2188-2) contains supplementary material, which is available to authorized users.
Published:
February 22, 2016
Title:
PTEN deficiency promotes macrophage infiltration and hypersensitivity of prostate cancer to IAP antagonist/radiation combination therapy
Authors:
Armstrong, Chris W. D.; Maxwell, Pamela J.; Ong, Chee Wee; Redmond, Kelly M.; McCann, Christopher; Neisen, Jessica; Ward, George A.; Chessari, Gianni; Johnson, Christopher; Crawford, Nyree T.; LaBonte, Melissa J.; Prise, Kevin M.; Robson, Tracy; Salto-Tellez, Manuel; Longley, Daniel B.; Waugh, David J. J.
Abstract:
PTEN loss is prognostic for patient relapse post-radiotherapy in prostate cancer (CaP). Infiltration of tumor-associated macrophages (TAMs) is associated with reduced disease-free survival following radical prostatectomy. However, the association between PTEN loss, TAM infiltration and radiotherapy response of CaP cells remains to be evaluated. Immunohistochemical and molecular analysis of surgically-resected Gleason 7 tumors confirmed that PTEN loss correlated with increased CXCL8 expression and macrophage infiltration. However PTEN status had no discernable correlation with expression of other inflammatory markers by CaP cells, including TNF-α. In vitro, exposure to conditioned media harvested from irradiated PTEN null CaP cells induced chemotaxis of macrophage-like THP-1 cells, a response partially attenuated by CXCL8 inhibition. Co-culture with THP-1 cells resulted in a modest reduction in the radio-sensitivity of DU145 cells. Cytokine profiling revealed constitutive secretion of TNF-α from CaP cells irrespective of PTEN status and IR-induced TNF-α secretion from THP-1 cells. THP-1-derived TNF-α increased NFκB pro-survival activity and elevated expression of anti-apoptotic proteins including cellular inhibitor of apoptosis protein-1 (cIAP-1) in CaP cells, which could be attenuated by pre-treatment with a TNF-α neutralizing antibody. Treatment with a novel IAP antagonist, AT-IAP, decreased basal and TNF-α-induced cIAP-1 expression in CaP cells, switched TNF-α signaling from pro-survival to pro-apoptotic and increased radiation sensitivity of CaP cells in co-culture with THP-1 cells. We conclude that targeting cIAP-1 can overcome apoptosis resistance of CaP cells and is an ideal approach to exploit high TNF-α signals within the TAM-rich microenvironment of PTEN-deficient CaP cells to enhance response to radiotherapy.
Published:
February 15, 2016
Title:
Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors: a meta-analysis of randomised controlled trials
Authors:
Mansoor, Nadia; Vinknes, Kathrine J.; Veierød, Marit B.; Retterstøl, Kjetil
Abstract:
Abstract The effects of low-carbohydrate (LC) diets on body weight and cardiovascular risk are unclear, and previous studies have found varying results. Our aim was to conduct a meta-analysis of randomised controlled trials (RCT), assessing the effects of LC diets v . low-fat (LF) diets on weight loss and risk factors of CVD. Studies were identified by searching MEDLINE, Embase and Cochrane Trials. Studies had to fulfil the following criteria: a RCT; the LC diet was defined in accordance with the Atkins diet, or carbohydrate intake of
Published:
February 13, 2016
Title:
The Radiocarbon Approach to Neanderthals in a Carnivore Den Site: a Well-Defined Chronology for Teixoneres Cave (Moià, Barcelona, Spain)
Authors:
Talamo, Sahra; Blasco, Ruth; Rivals, Florent; Picin, Andrea; María Gema, Chacón; Iriarte, Eneko; López-García, Juan; Blain, Hugues-Alexandre; Arilla, Maite; Rufà, Anna; Sánchez-Hernández, Carlos; Andres, Miriam; Camarós, Edgard; Ballesteros, Anna; Cebrià, Artur; Rosell Ardèvol, Jordi; Hublin, Jean-Jacques
Abstract:
During the Middle Paleolithic period, carnivores and hominids periodically occupied the same areas at different times and each predator generated significant palimpsests, rendering difficult their archaeological interpretation. Teixoneres Cave, a carnivore den site, located in the northeastern part of the Iberian Peninsula, demonstrates that it is possible to overcome these problems by using a careful strategy in selecting samples for radiocarbon dating, in order to produce an accurate chronology of the site in question and certainly attest the human occupation.
Published:
February 11, 2016
Title:
The moderate essential amino acid restriction entailed by low-protein vegan diets may promote vascular health by stimulating FGF21 secretion
Authors:
McCarty, Mark F.
Abstract:
The serum total and LDL cholesterol levels of long-term vegans tend to be very low. The characteristically low ratio of saturated to unsaturated fat in vegan diets, and the absence of cholesterol in such diets, clearly contribute to this effect. But there is reason to suspect that the quantity and composition of dietary protein also play a role in this regard. Vegan diets of moderate protein intake tend to be relatively low in certain essential amino acids, and as a result may increase hepatic activity of the kinase GCN2, which functions as a gauge of amino acid status. GCN2 activation boosts the liver's production of fibroblast growth factor 21 (FGF21), a factor which favorably affects serum lipids and metabolic syndrome. The ability of FGF21 to decrease LDL cholesterol has now been traced to at least two mechanisms: a suppression of hepatocyte expression of sterol response element-binding protein-2 (SREBP-2), which in turn leads to a reduction in cholesterol synthesis; and up-regulated expression of hepatocyte LDL receptors, reflecting inhibition of a mechanism that promotes proteasomal degradation of these receptors. In mice, the vascular benefits of FGF21 are also mediated by favorable effects on adipocyte function - most notably, increased adipocyte secretion of adiponectin, which directly exerts anti-inflammatory effects on the vasculature which complement the concurrent reduction in LDL particles in preventing or reversing atherosclerosis. If, as has been proposed, plant proteins preferentially stimulate glucagon secretion owing to their amino acid composition, this would represent an additional mechanism whereby plant protein promotes FGF21 activity, as glucagon acts on the liver to boost transcription of the FGF21 gene.
Published:
February 11, 2016
Title:
A Comprehensive Lifestyle Peer Group–Based Intervention on Cardiovascular Risk Factors: The Randomized Controlled Fifty-Fifty Program
Authors:
Gómez-Pardo, Emilia; Fernández-Alvira, Juan Miguel; Vilanova, Marta; Haro, Domingo; Martínez, Ramona; Carvajal, Isabel; Carral, Vanesa; Rodríguez, Carla; Miguel, Mercedes de; Bodega, Patricia; Santos-Beneit, Gloria; Peñalvo, Jose Luis; Marina, Iñaki; Pérez-Farinós, Napoleón; Re, Marian Dal; Villar, Carmen; Robledo, Teresa; Vedanthan, Rajesh; Bansilal, Sameer; Fuster, Valentin
Abstract:
Background Cardiovascular diseases stem from modifiable risk factors. Peer support is a proven strategy for many chronic illnesses. Randomized trials assessing the efficacy of this strategy for global cardiovascular risk factor modification are lacking. Objectives This study assessed the hypothesis that a peer group strategy would help improve healthy behaviors in individuals with cardiovascular risk factors. Methods A total of 543 adults 25 to 50 years of age with at least 1 risk factor were recruited; risk factors included hypertension (20%), overweight (82%), smoking (31%), and physical inactivity (81%). Subjects were randomized 1:1 to a peer group–based intervention group (IG) or a self-management control group (CG) for 12 months. Peer-elected leaders moderated monthly meetings involving role-play, brainstorming, and activities to address emotions, diet, and exercise. The primary outcome was mean change in a composite score related to blood pressure, exercise, weight, alimentation, and tobacco (Fuster-BEWAT score, 0 to 15). Multilevel models with municipality as a cluster variable were applied to assess differences between groups. Results Participants’ mean age was 42 ± 6 years, 71% were female, and they had a mean baseline Fuster-BEWAT score of 8.42 ± 2.35. After 1 year, the mean scores were significantly higher in the IG (n = 277) than in the CG (n = 266) (IG mean score: 8.84; 95% confidence interval (CI): 8.37 to 9.32; CG mean score: 8.17; 95% CI: 7.55 to 8.79; p = 0.02). The increase in the overall score was significantly larger in the IG compared with the CG (difference: 0.75; 95% CI: 0.32 to 1.18; p = 0.02). The mean improvement in the individual components was uniformly greater in the IG, with a significant difference for the tobacco component. Conclusions The peer group intervention had beneficial effects on cardiovascular risk factors, with significant improvements in the overall score and specifically on tobacco cessation. A follow-up assessment will be performed 1 year after the final assessment reported here to determine long-term sustainability of the improvements associated with peer group intervention. (Peer-Group-Based Intervention Program [Fifty-Fifty]; NCT02367963)
Published:
February 8, 2016
Title:
Imaging colon cancer development in mice: IL-6 deficiency prevents adenoma in azoxymethane-treated Smad3 knockouts
Authors:
Harpel, Kaitlin; Leung, Sarah; Rice, Photini Faith; Jones, Mykella; Barton, Jennifer K.; Bommireddy, Ramireddy
Abstract:
The development of colorectal cancer in the azoxymethane-induced mouse model can be observed by using a miniaturized optical coherence tomography (OCT) imaging system. This system is uniquely capable of tracking disease development over time, allowing for the monitoring of morphological changes in the distal colon due to tumor development and the presence of lymphoid aggregates. By using genetically engineered mouse models deficient in Interleukin 6 (IL-6) and Smad family member 3 (Smad3), the role of inflammation on tumor development and the immune system can be elucidated. Smad3 knockout mice develop inflammatory response, wasting, and colitis associated cancer while deficiency of proinflammatory cytokine IL-6 confers resistance to tumorigenesis. We present pilot data showing that the Smad3 knockout group had the highest tumor burden, highest spleen weight, and lowest thymus weight. The IL-6 deficiency in Smad3 knockout mice prevented tumor development, splenomegaly, and thymic atrophy. This finding suggests that agents that inhibit IL-6 (e.g. anti-IL-6 antibody, non-steroidal anti-inflammatory drugs [NSAIDs], etc.) could be used as novel therapeutic agents to prevent disease progression and increase the efficacy of anti-cancer agents. OCT can also be useful for initiating early therapy and assessing the benefit of combination therapy targeting inflammation.
Published:
February 6, 2016
Title:
Proteomic Biomarker Discovery in 1000 Human Plasma Samples with Mass Spectrometry
Authors:
Cominetti, Ornella; Núñez Galindo, Antonio; Corthésy, John; Oller Moreno, Sergio; Irincheeva, Irina; Valsesia, Armand; Astrup, Arne; Saris, Wim H. M.; Hager, Jörg; Kussmann, Martin; Dayon, Loïc
Abstract:
The overall impact of proteomics on clinical research and its translation has lagged behind expectations. One recognized caveat is the limited size (subject numbers) of (pre)clinical studies performed at the discovery stage, the findings of which fail to be replicated in larger verification/validation trials. Compromised study designs and insufficient statistical power are consequences of the to-date still limited capacity of mass spectrometry (MS)-based workflows to handle large numbers of samples in a realistic time frame, while delivering comprehensive proteome coverages. We developed a highly automated proteomic biomarker discovery workflow. Herein, we have applied this approach to analyze 1000 plasma samples from the multicentered human dietary intervention study "DiOGenes". Study design, sample randomization, tracking, and logistics were the foundations of our large-scale study. We checked the quality of the MS data and provided descriptive statistics. The data set was interrogated for proteins with most stable expression levels in that set of plasma samples. We evaluated standard clinical variables that typically impact forthcoming results and assessed body mass index-associated and gender-specific proteins at two time points. We demonstrate that analyzing a large number of human plasma samples for biomarker discovery with MS using isobaric tagging is feasible, providing robust and consistent biological results.
Published:
February 4, 2016
Title:
Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents
Authors:
Punja, Salima; Shamseer, Larissa; Hartling, Lisa; Urichuk, Liana; Vandermeer, Ben; Nikles, Jane; Vohra, Sunita
Abstract:
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric conditions affecting children and adolescents. Amphetamines are among the most commonly prescribed medications to manage ADHD. There are three main classes of amphetamines: dexamphetamine, lisdexamphetamine and mixed amphetamine salts, which can be further broken down into short- and long-acting formulations. A systematic review assessing their efficacy and safety in this population has never been conducted. OBJECTIVES: To assess the efficacy and safety of amphetamines for ADHD in children and adolescents. SEARCH METHODS: In August 2015 we searched CENTRAL, Ovid MEDLINE, Embase, PsycINFO, ProQuest Dissertation and Theses, and the Networked Digital Library of Theses and Dissertations. We also searched ClinicalTrials.gov, and checked the reference lists of relevant studies and reviews identified by the searches. No language or date restrictions were applied. SELECTION CRITERIA: Parallel-group and cross-over randomized controlled trials (RCTs) comparing amphetamine derivatives against placebo in a pediatric population (< 18 years) with ADHD. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data on participants, settings, interventions, methodology, and outcomes for each included study. For continuous outcomes, we calculated the standardized mean difference (SMD) and for dichotomous outcomes we calculated the risk ratio (RR). Where possible, we conducted meta-analyses using a random-effects model. We also performed a meta-analysis of the most commonly reported adverse events in the primary studies. MAIN RESULTS: We included 23 trials (8 parallel-group and 15 cross-over trials), with 2675 children aged three years to 17 years. All studies compared amphetamines to placebo. Study durations ranged from 14 days to 365 days, with the majority lasting less than six months. Most studies were conducted in the United States; three studies were conducted across Europe. We judged 11 included studies to be at a high risk of bias due to insufficient blinding methods, failing to account for dropouts and exclusions from the analysis, and failing to report on all outcomes defined a priori. We judged the remaining 12 studies to be at unclear risk of bias due to inadequate reporting.Amphetamines improved total ADHD core symptom severity according to parent ratings (SMD -0.57; 95% confidence interval (CI) -0.86 to -0.27; 7 studies; 1247 children/adolescents; very low quality evidence), teacher ratings (SMD -0.55; 95% CI -0.83 to -0.27; 5 studies; 745 children/adolescents; low quality evidence), and clinician ratings (SMD -0.84; 95% CI -1.32 to -0.36; 3 studies; 813 children/adolescents; very low quality evidence). In addition, the proportion of responders as rated by the Clinical Global Impression - Improvement (CGI-I) scale was higher when children were taking amphetamines (RR 3.36; 95% CI 2.48 to 4.55; 9 studies; 2207 children/adolescents; very low quality evidence).The most commonly reported adverse events included decreased appetite, insomnia/trouble sleeping, abdominal pain, nausea/vomiting, headaches, and anxiety. Amphetamines were associated with a higher proportion of participants experiencing decreased appetite (RR 6.31; 95% CI 2.58 to 15.46; 11 studies; 2467 children/adolescents), insomnia (RR 3.80; 95% CI 2.12 to 6.83; 10 studies; 2429 children/adolescents), and abdominal pain (RR 1.44; 95% CI 1.03 to 2.00; 10 studies; 2155 children/adolescents). In addition, the proportion of children who experienced at least one adverse event was higher in the amphetamine group (RR 1.30; 95% CI 1.18 to 1.44; 6 studies; 1742 children/adolescents; low quality evidence).We performed subgroup analyses for amphetamine preparation (dexamphetamine, lisdexamphetamine, mixed amphetamine salts), amphetamine release formulation (long acting versus short acting), and funding source (industry versus non industry). Between-group differences were observed for proportion of participants experiencing decreased appetite in both the amphetamine preparation (P
Published:
February 3, 2016
Title:
The origin and divergence of Gobioninae fishes (Teleostei: Cyprinidae) based on complete mitochondrial genome sequences
Authors:
Zhao, Jinfeng; Xu, Dandan; Zhao, Kai; Diogo, Rui; Yang, Jin-Quan; Peng, Zuogang
Abstract:
The gudgeons (subfamily Gobioninae) are a group of cypri-nid fishes primarily distributed in East Asia. However, studies on their origins and divergence are scarce. Here the whole mitochondrial genome sequences of 27 gudgeon species (including one newly determined), 22 other cyprinid species, and two non-cyprinids as outgroups are applied to infer the evolution of the gudgeons. Based on Bayesian and maximum likelihood phylogenetic analyses, the gudgeons were determined to be a monophyletic group which can be further subdivided into four monophyletic clades with strong supports. The divergence times of the gudgeons were estimated using a relaxed molecular clock method; the results indicate that these fishes originated in the early Paleocene (approx. 63.5 Mya) and that the basal Hemibarbus group diverged from the other gudgeon fishes (approx. 58.3 Mya). As an independent group the Coreius began to diverge from the remaining two groups (approx. 54.6 Mya); the most derived two groups diverged from each other (approx. 53.6 Mya). The divergences of the four gudgeon groups were within a relatively short time frame (approx. 58–53 Mya). Based on the reconstruction of evolutionary trends of gudgeon habitat, evidence is provided that supports the origin and differentiation of this fauna as being associated with some special paleo-environmental events occurring from the early Pale-ocene to the Pliocene. The study represents comprehensive molecular dating and character evolution analyses of the gudgeons, and providing a valuable framework for future research in the evolution of the Gobioninae fishes.
Published:
February 3, 2016
Title:
Association of Seafood Consumption, Brain Mercury Level, and APOE ε4 Status With Brain Neuropathology in Older Adults
Authors:
Morris, Martha Clare; Brockman, John; Schneider, Julie A.; Wang, Yamin; Bennett, David A.; Tangney, Christy C.; Rest, Ondine van de
Abstract:
Importance
Seafood consumption is promoted for its many health benefits even though its contamination by mercury, a known neurotoxin, is a growing concern.
Objective
To determine whether seafood consumption is correlated with increased brain mercury levels and also whether seafood consumption or brain mercury levels are correlated with brain neuropathologies.
Design, Setting, and Participants
Cross-sectional analyses of deceased participants in the Memory and Aging Project clinical neuropathological cohort study, 2004-2013. Participants resided in Chicago retirement communities and subsidized housing. The study included 286 autopsied brains of 554 deceased participants (51.6%). The mean (SD) age at death was 89.9 (6.1) years, 67% (193) were women, and the mean (SD) educational attainment was 14.6 (2.7) years.
Exposures
Seafood intake was first measured by a food frequency questionnaire at a mean of 4.5 years before death.
Main Outcomes and Measures
Dementia-related pathologies assessed were Alzheimer disease, Lewy bodies, and the number of macroinfarcts and microinfarcts. Dietary consumption of seafood and n-3 fatty acids was annually assessed by a food frequency questionnaire in the years before death. Tissue concentrations of mercury and selenium were measured using instrumental neutron activation analyses.
Results
Among the 286 autopsied brains of 544 participants, brain mercury levels were positively correlated with the number of seafood meals consumed per week (ρ = 0.16;P = .02). In models adjusted for age, sex, education, and total energy intake, seafood consumption (≥ 1 meal[s]/week) was significantly correlated with less Alzheimer disease pathology including lower density of neuritic plaques (β = −0.69 score units [95% CI, −1.34 to −0.04]), less severe and widespread neurofibrillary tangles (β = −0.77 score units [95% CI, −1.52 to −0.02]), and lower neuropathologically defined Alzheimer disease (β = −0.53 score units [95% CI, −0.96 to −0.10]) but only among apolipoprotein E (APOE ε4) carriers. Higher intake levels of α-linolenic acid (18:3 n-3) were correlated with lower odds of cerebral macroinfarctions (odds ratio for tertiles 3 vs 1, 0.51 [95% CI, 0.27 to 0.94]). Fish oil supplementation had no statistically significant correlation with any neuropathologic marker. Higher brain concentrations of mercury were not significantly correlated with increased levels of brain neuropathology.
Conclusions and Relevance
In cross-sectional analyses, moderate seafood consumption was correlated with lesser Alzheimer disease neuropathology. Although seafood consumption was also correlated with higher brain levels of mercury, these levels were not correlated with brain neuropathology.
Published:
February 1, 2016
Title:
Quality of life in women with lipoedema: a contextual behavioral approach
Authors:
Dudek, Joanna E.; Białaszek, Wojciech; Ostaszewski, Paweł
Abstract:
Purpose Lipoedema is a chronic, progressive adipose disorder of unknown etiology, often underdiagnosed or misdiagnosed as obesity. It manifests itself with accumulation of the fat in lower parts of the body and associated edema and, due to numerous physical and psychological consequences, affects the quality of life (QOL) of those who suffer. The aim of this study was to investigate the psychological factors that might have an impact on the QOL of women with lipoedema from the contextual behavioral viewpoint. MethodsIn an Internet-based cross-sectional study, women suffering from lipoedema (N = 120) were asked to fill in questionnaires assessing: symptom severity, QOL (WHOQOL-BREF), satisfaction with life (SWLS), psychological flexibility (Acceptance and Action Questionnaire-II), social connectedness (Social Connectedness Scale-Revised) and other psychological factors. The majority of participants were from the USA, the UK, and Australia.ResultsMultiple hierarchical regression analyses showed that a higher level of QOL was predicted by higher levels of psychological flexibility and social connectedness, while controlling for symptom severity. Higher level of SWL was predicted only by higher level of social connectedness.ConclusionsAcceptance and Commitment Therapy with psychological flexibility as the target of change and Functional Analytic Psychotherapy with social connectedness as the target of change might be useful in treating women with lipoedema; however, further research in this area is needed. The authors conclude that psychological and biomedical interventions for women with lipoedema and their QOL merit more attention from researchers and the medical community than is currently received.
Published:
January 31, 2016
Title:
Type 2 Diabetes and Depression: A Pilot Trial of an Integrated Self-management Intervention for Latino Immigrants
Authors:
Kaltman, Stacey; Serrano, Adriana; Talisman, Nicholas; Magee, Michelle F.; Cabassa, Leopoldo J.; Pulgar-Vidal, Olga; Peraza, Dorys
Abstract:
PurposeThe purpose of the current study was to determine the feasibility, acceptability, and preliminary effectiveness of an integrated self-management intervention that simultaneously targets diabetes and depression self-management in a primary care clinic that serves the Latino immigrant community.MethodsThe integrated intervention included behavioral activation and motivational interviewing techniques. It was developed with patient, family member, and provider stakeholders, and it comprised 6 individual sessions, followed by 2 monthly booster sessions. Eighteen Latino immigrants participated in an open trial of the intervention. A1C levels were examined at baseline and postintervention. Participants also completed measures of depression, diabetes self-management behaviors, patient activation, and diabetes-related self-efficacy and gave open-ended feedback about the intervention.ResultsFeasibility of delivering the intervention in the primary care setting and acceptability to the target population were demonstrated. Among participants completing the intervention, A1C levels decreased significantly from baseline. A significant reduction in depressive symptoms and an improvement in diabetes self-management behaviors, patient activation, and diabetes-related self-efficacy were observed. Qualitative responses from participants indicated unilateral positive responses to the intervention and endorsed its continuation in the clinic.ConclusionsThis pilot trial demonstrated the feasibility and acceptability of an integrated self-management intervention for diabetes and depression. In addition, preliminary data suggest that the intervention may have a positive impact on diabetes and depression-related outcomes. Further evaluation is warranted.
Published:
January 31, 2016
Title:
Estrogen receptor α in cancer associated fibroblasts suppresses prostate cancer invasion via reducing CCL5, IL6 and macrophage infiltration in the tumor microenvironment
Authors:
Yeh, Chiuan-Ren; Slavin, Spencer; Da, Jun; Hsu, Iawen; Luo, Jie; Xiao, Guang-Qian; Ding, Jie; Chou, Fu-Ju; Yeh, Shuyuan
Abstract:
BACKGROUND: Cancer associated fibroblasts (CAF) play important roles in tumor growth that involves inflammation and epithelial cell differentiation. Early studies suggested that estrogen receptor alpha (ERα) was expressed in stromal cells in normal prostates and prostate cancer (PCa), but the detailed functions of stromal ERα in the PCa remain to be further elucidated. METHODS: Migration and invasion assays demonstrated the presence of high levels of ERα in CAF cells (CAF.ERα(+)) suppressed PCa invasion via influencing the infiltration of tumor associated macrophages. ERα decreased CAF CCL5 secretion via suppressing the CCL5 promoter activity was examined by luciferase assay. ERα decreased CCL5 and IL-6 expression in conditioned media that was collected from CAF cell only or CAF cell co-cultured with macrophages as measured by ELISA assay. RESULTS: Both in vitro and in vivo studies demonstrated CAF.ERα(+) led to a reduced macrophage migration toward PCa via inhibiting CAF cells secreted chemokine CCL5. This CAF.ERα(+) suppressed macrophage infiltration affected the neighboring PCa cells invasion and the reduced invasiveness of PCa cells are at least partly due to reduced IL6 expression in the macrophages and CAF. CONCLUSION: Our data suggest that CAF ERα could be applied as a prognostic marker to predict cancer progression, and targeting CCL5 and IL6 may be applied as an alternative therapeutic approach to reduce M2 type macrophages and PCa invasion in PCa patients with low or little ERα expression in CAF cells.
Published:
January 19, 2016
Title:
Reply to Underdown and Oppenheimer: Roles of selection, plasticity, and genetics in the integration of human pelvis shape and head size
Authors:
Fischer, Barbara; Mitteroecker, Philipp
Abstract:
In our paper (1) we report on a previously unknown association between human pelvis shape, head size, and stature that appears to ameliorate—but in no way resolve—the obstetric dilemma. In an interesting response to this article, Underdown and Oppenheimer (2) emphasize that “one must explicitly consider whether the suggested relationship is an evolutionary-selective phenomenon or an analytic artifact produced by combining multiple anatomically related variables (each of which potentially underwent differential patterns of selection) or plasticity in the individual.” Independent selection of pelvis shape, stature, and head size would produce covariation of average population phenotypes across evolutionary time, but not of individual phenotypes … [↵][1]1To whom correspondence should be addressed. Email: b.fischer{at}univie.ac.at. [1]: #xref-corresp-1-1
Published:
January 18, 2016
Title:
A Comparison of Ancient Greek and Roman Sports Diets with Modern Day Practices
Authors:
Harrison, Adrian Paul; Bartels, Else Marie
Abstract:
With the preparations for the Olympics 2016 in Rio came a series of demands to the sports world in terms of attaining optimal physical performance for the many disciplines represented at today’s Olympics. In the light of this, we have focused on the dietary and physiological requirements of a modern Olympic athlete and contrast these with those of ancient Greek and Roman athletes. Our particular emphasis has been on the source of nutrients, historical dietary trends, and the search for the optimal sports diet, that is to say a diet that will ensure the attainment of an athlete’s full potential. In reality, nothing has changed between the ancient and modern athletes. To be optimal, a sports diet should be nutritionally balanced, whilst accommodating the genetic and environmental requirements, the gender and age needs, the demands of the sports discipline, as well as addressing any cultural dietary restrictions.
Published:
January 14, 2016
Title:
A Comparison of Ancient Greek and Roman Sports Diets with Modern Day Practices
Authors:
Harrison, Adrian Paul; Bartels, Else Marie
Abstract:
With the preparations for the Olympics 2016 in Rio came a series of demands to the sports world in terms of attaining optimal physical performance for the many disciplines represented at today’s Olympics. In the light of this, we have focused on the dietary and physiological requirements of a modern Olympic athlete and contrast these with those of ancient Greek and Roman athletes. Our particular emphasis has been on the source of nutrients, historical dietary trends, and the search for the optimal sports diet, that is to say a diet that will ensure the attainment of an athlete’s full potential. In reality, nothing has changed between the ancient and modern athletes. To be optimal, a sports diet should be nutritionally balanced, whilst accommodating the genetic and environmental requirements, the gender and age needs, the demands of the sports discipline, as well as addressing any cultural dietary restrictions.
Published:
January 14, 2016
Title:
Preliminary analysis of dental cementum of Lama guanicoe for the estimation of age and season at death: Studies of modern specimens and further archaeological applications
Authors:
Gourichon, Lionel; Parmigiani, Vanesa
Abstract:
Cementum increment analysis has been applied with success in mammals since several decades for both current wildlife studies and studies of fauna from archaeological sites. This method provides estimations about the age and the season at death of ungulates recovered at archaeological sites and can be used to explore important issues such as hunting or herding strategies, settlement patterns and mobility.Over the past 30 years cementum studies have expanded the range of mammalian species for which the method can be applied in archaeology. However, very few data are today available about the guanaco (Lama guanicoe) which was the dominant large ungulate in South America in prehistoric and historical times. The purpose of our project is to develop and improve the cementum increment analysis for this species using modern reference data sets before its application to archaeological assemblages. The present paper presents the preliminary results obtained from the study of canines and incisors of modern specimens and will discuss the potentiality and limitations of the technique.
Published:
January 14, 2016
Title:
Two c-Myc binding sites are crucial in upregulating the expression of human phospholipid scramblase 1 gene
Authors:
Vinnakota, Janaki Manoja; Gummadi, Sathyanarayana N.
Abstract:
Human phospholipid scramblase 1 (hPLSCR1) is a type II endofacial membrane protein which mediates bi-directional transport of phospholipids across the plasma membrane. hPLSCR1, a multifunctional protein with variety of roles in apoptosis, tumor progression, cell signaling and anti-viral defense. The expression of such a multifunctional protein should be under tight regulation. Apart from a single report showing snail mediated down regulation of hPLSCR1, the molecular mechanisms regulating the expression of scramblases are not well elucidated. In this study we identified c-Myc as a transcriptional regulator of hPLSCR1. Transcription factor prediction tool ConSite predicted three binding sites for c-Myc. Reporter gene assays and western blot analysis revealed c-Myc mediated up regulation of hPLSCR1 expression. Deletion construct −790 lacking one c-Myc binding site showed a 27% decrease in promoter activity while deletion construct −469 lacking two c-Myc binding sites showed a 62% decrease in promoter activity. Site directed mutagenesis revealed the importance of c-Myc binding sites from −751 to −756 and −548 to −553 on the promoter of hPLSCR1in transcriptionally regulating the expression of hPLSCR1. The results were further confirmed by shRNA mediated knock down of endogenous c-Myc and in vivo interactions by ChIP assay.
Published:
January 14, 2016
Title:
Weight Loss and Health Status 3 Years after Bariatric Surgery in Adolescents
Authors:
Inge, Thomas H.; Courcoulas, Anita P.; Jenkins, Todd M.; Michalsky, Marc P.; Helmrath, Michael A.; Brandt, Mary L.; Harmon, Carroll M.; Zeller, Meg H.; Chen, Mike K.; Xanthakos, Stavra A.; Horlick, Mary; Buncher, C. Ralph
Abstract:
BACKGROUND Bariatric surgery is increasingly considered for the treatment of adolescents with severe obesity, but few prospective adolescent-specific studies examining the efficacy and safety of weight-loss surgery are available to support clinical decision making. METHODS We prospectively enrolled 242 adolescents undergoing weight-loss surgery at five U.S. centers. Patients undergoing Roux-en-Y gastric bypass (161 participants) or sleeve gastrectomy (67) were included in the analysis. Changes in body weight, coexisting conditions, cardiometabolic risk factors, and weight-related quality of life and postoperative complications were evaluated through 3 years after the procedure. RESULTS The mean (±SD) baseline age of the participants was 17±1.6 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 53; 75% of the participants were female, and 72% were white. At 3 years after the procedure, the mean weight had decreased by 27% (95% confidence interval [CI], 25 to 29) in the total cohort, by 28% (95% CI, 25 to 30) among participants who underwent gastric bypass, and by 26% (95% CI, 22 to 30) among those who underwent sleeve gastrectomy. By 3 years after the procedure, remission of type 2 diabetes occurred in 95% (95% CI, 85 to 100) of participants who had had the condition at baseline, remission of abnormal kidney function occurred in 86% (95% CI, 72 to 100), remission of prediabetes in 76% (95% CI, 56 to 97), remission of elevated blood pressure in 74% (95% CI, 64 to 84), and remission of dyslipidemia in 66% (95% CI, 57 to 74). Weight-related quality of life also improved significantly. However, at 3 years after the bariatric procedure, hypoferritinemia was found in 57% (95% CI, 50 to 65) of the participants, and 13% (95% CI, 9 to 18) of the participants had undergone one or more additional intraabdominal procedures. CONCLUSIONS In this multicenter, prospective study of bariatric surgery in adolescents, we found significant improvements in weight, cardiometabolic health, and weight-related quality of life at 3 years after the procedure. Risks associated with surgery included specific micro-nutrient deficiencies and the need for additional abdominal procedures. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; Teen-LABS ClinicalTrials.gov number, NCT00474318.)
Published:
January 13, 2016
Title:
THE EMERGING HALLMARKS OF CANCER METABOLISM
Authors:
Pavlova, Natalya N.; Thompson, Craig B.
Abstract:
Tumorigenesis is dependent on the reprogramming of cellular metabolism as both direct and indirect consequence of oncogenic mutations. A common feature of cancer cell metabolism is the ability to acquire necessary nutrients from a frequently nutrient-poor environment and utilize these nutrients to both maintain viability and build new biomass. The alterations in intracellular and extracellular metabolites that can accompany cancer-associated metabolic reprogramming have profound effects on gene expression, cellular differentiation and the tumor microenvironment. In this Review, we have organized known cancer-associated metabolic changes into six hallmarks: (1) deregulated uptake of glucose and amino acids, (2) use of opportunistic modes of nutrient acquisition, (3) use of glycolysis/TCA cycle intermediates for biosynthesis and NADPH production, (4) increased demand for nitrogen, (5) alterations in metabolite-driven gene regulation, and (6) metabolic interactions with the microenvironment. While few tumors display all six hallmarks, most display several. The specific hallmarks exhibited by an individual tumor may ultimately contribute to better tumor classification and aid in directing treatment.
Published:
January 11, 2016
Title:
Milestones in the history of diabetes mellitus: The main contributors
Authors:
Karamanou, Marianna; Protogerou, Athanase; Tsoucalas, Gregory; Androutsos, George; Poulakou-Rebelakou, Effie
Abstract:
Diabetes mellitus is a group of metabolic diseases involving carbohydrate, lipid, and protein metabolism. It is characterized by persistent hyperglycemia which results from defects in insulin secretion, or action or both. Diabetes mellitus has been known since antiquity. Descriptions have been found in the Egyptian papyri, in ancient Indian and Chinese medical literature, as well as, in the work of ancient Greek and Arab physicians. In the 2nd century AD Aretaeus of Cappadocia provided the first accurate description of diabetes, coining the term diabetes, while in 17th century Thomas Willis added the term mellitus to the disease, in an attempt to describe the extremely sweet taste of the urine. The important work of the 19th century French physiologist Claude Bernard, on the glycogenic action of the liver, paved the way for further progress in the study of the disease. In 1889, Oskar Minkowski and Joseph von Mering performed their famous experiment of removing the pancreas from a dog and producing severe and fatal diabetes. In 1921, Frederick Banting and Charles Best extended Minkowski’s and Mering’s experiment. They isolated insulin from pancreatic islets and administrated to patients suffering from type 1 diabetes, saving thus the lives of millions and inaugurating a new era in diabetes treatment.
Published:
January 9, 2016
Title:
Choline, Its Potential Role in Nonalcoholic Fatty Liver Disease, and the Case for Human and Bacterial Genes12
Authors:
Sherriff, Jill L; O’Sullivan, Therese A; Properzi, Catherine; Oddo, Josephine-Lee; Adams, Leon A
Abstract:
Our understanding of the impact of poor hepatic choline/phosphatidylcholine availability in promoting the steatosis characteristic of human nonalcoholic fatty liver disease (NAFLD) has recently advanced and possibly relates to phosphatidylcholine/phosphatidylethanolamine concentrations in various, membranes as well as cholesterol dysregulation. A role for choline/phosphatidylcholine availability in the progression of NAFLD to liver injury and serious hepatic consequences in some individuals requires further elucidation. There are many reasons for poor choline/phosphatidylcholine availability in the liver, including low intake, estrogen status, and genetic polymorphisms affecting, in particular, the pathway for hepatic de novo phosphatidylcholine synthesis. In addition to free choline, phosphatidylcholine has been identified as a substrate for trimethylamine production by certain intestinal bacteria, thereby reducing host choline bioavailability and providing an additional link to the increased risk of cardiovascular disease faced by those with NAFLD. Thus human choline requirements are highly individualized and biomarkers of choline status derived from metabolomics studies are required to predict those at risk of NAFLD induced by choline deficiency and to provide a basis for human intervention trials.
Published:
January 6, 2016
Title:
Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip
Authors:
Kim, Hyun Jung; Li, Hu; Collins, James J.; Ingber, Donald E.
Abstract:
A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1β, and TNF-α) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models.
Published:
January 4, 2016
Title:
A child with type 1 diabetes mellitus (T1DM) successfully treated with the Paleolithic ketogenic diet: A 19-month insulin freedom
Authors:
Tóth, Csaba; Clemens, Zsofia
Abstract:
Introduction: Currently, type 1 diabetes mellitus (T1DM) is treated with insulin and a high carbohydrate diet. In literature, there are studies indicating that low carbohydrate diets may be beneficial in reducing hypoglycemic episodes as well as the need for insulin. Previously, we reported a case of a 19-year-old T1DM patient who was successfully treated with a modified version of the ketogenic diet we refer to as the Paleolithic ketogenic diet. Case Report: A nine-year-old child with T1DM who initially was on an insulin regime with high carbohydrate diet then was put on the Paleolithic ketogenic diet. Following dietary shift glucose levels normalized and he was able to discontinue insulin. No hypoglycemic episodes occurred on the diet and several other benefits were achieved including improved physical fitness, reduction of upper respiratory tract infections and eczema. Currently, he is on the diet for 19 months. Conclusion: Adopting the Paleolithic ketogenic diet ensured normoglycemia without the use of external insulin. The diet was sustainable on the long-term. Neither complications nor side effects emerged on the diet. Keywords: C peptide, Ketogenic diet, Ketosis, Low carbohydrate diet, Paleolithic diet, Paleolithic ketogenic diet, Type 1 diabetes mellitus
Published:
December 31, 2015
Title:
Central activation of TRPV1 and TRPA1 by novel endogenous agonists contributes to mechanical and thermal allodynia after burn injury
Authors:
Green, Dustin P; Ruparel, Shivani; Gao, Xiaoli; Ruparel, Nikita; Patil, Mayur; Akopian, Armen; Hargreaves, Kenneth M
Abstract:
The primary complaint of burn victims is an intense, often devastating spontaneous pain, with persistence of mechanical and thermal allodynia. The transient receptor potential channels, TRPV1 and TRPA1, are expressed by a subset of nociceptive sensory neurons and contribute to inflammatory hypersensitivity. Although their function in the periphery is well known, a role for these TRP channels in central pain mechanisms is less well defined. Lipid agonists of TRPV1 are released from peripheral tissues via enzymatic oxidation after burn injury; however, it is not known if burn injury triggers the release of oxidized lipids in the spinal cord. Accordingly, we evaluated whether burn injury evoked the central release of oxidized lipids. Analysis of lipid extracts of spinal cord tissue with HPLC-MS revealed a significant increase in levels of the epoxide and diol metabolites of linoleic acid: 9,10-DiHOME, 12,13-DiHOME, 9(10)-EpOME, and 12(13)-EpOME, that was reduced after intrathecal (i.t.) injection of the oxidative enzyme inhibitor ketoconazole. Moreover, we found that these four lipid metabolites were capable of specifically activating both TRPV1 and TRPA1. Intrathecal injection of specific antagonists to TRPV1 (AMG-517) or TRPA1 (HC-030031) significantly reduced post-burn mechanical and thermal allodynia. Finally, i.t. injection of ketoconazole significantly reversed post-burn mechanical and thermal allodynia. Our data indicate that spinal cord TRPV1 and TRPA1 contributes to pain after burn and identifies a novel class of oxidized lipids elevated in the spinal cord after burn injury. Since the management of burn pain is problematic, these findings point to a novel approach for treating post-burn pain.
Published:
December 31, 2015
Title:
Diagnostic Metabolomic Blood Tests for Endoluminal Gastrointestinal Cancer—A Systematic Review and Assessment of Quality
Authors:
Antonowicz, Stefan; Kumar, Sacheen; Wiggins, Tom; Markar, Sheraz R.; Hanna, George B.
Abstract:
Advances in analytics have resulted in metabolomic blood tests being developed for the detection of cancer. This systematic review aims to assess the diagnostic accuracy of blood-based metabolomic biomarkers for endoluminal gastrointestinal (GI) cancer. Using endoscopic diagnosis as a reference standard, methodologic and reporting quality was assessed using validated tools, in addition to pathway-based informatics to biologically contextualize discriminant features. Twenty-nine studies (15 colorectal, 9 esophageal, 3 gastric, and 2 mixed) with data from 10,835 participants were included. All reported significant differences in hematologic metabolites. In pooled analysis, 246 metabolites were found to be significantly different after multiplicity correction. Incremental metabolic flux with disease progression was frequently reported. Two promising candidates have been validated in independent populations (both colorectal biomarkers), and one has been approved for clinical use. Networks analysis suggested modulation of elements of up to half of Edinburgh Human Metabolic Network subdivisions, and that the poor clinical applicability of commonly modulated metabolites could be due to extensive molecular interconnectivity. Methodologic and reporting quality was assessed as moderate-to-poor. Serum metabolomics holds promise for GI cancer diagnostics; however, future efforts must adhere to consensus standardization initiatives, utilize high-resolution discovery analytics, and compare candidate biomarkers with peer nonendoscopic alternatives. Cancer Epidemiol Biomarkers Prev; 25(1); 6–15. ©2015 AACR.
Published:
December 31, 2015
Title:
Eating like there's no tomorrow: Public awareness of the environmental impact of food and reluctance to eat less meat as part of a sustainable diet
Authors:
Macdiarmid, Jennie I.; Douglas, Flora; Campbell, Jonina
Abstract:
Reducing meat consumption is central to many of the scientific debates on healthy, sustainable diets because of the high environmental impact of meat production. Missing from these debates are the public perspectives about eating less meat and consideration of cultural and social values associated with meat. The aim of this study was to explore public awareness of the environmental impact of food and their willingness to reduce meat consumption. Twelve focus groups and four individual interviews were conducted with adults from a range of socio-economic groups living in both rural and urban settings in Scotland. Public understanding of the link between food, environment and climate change was explored, with a focus on meat and attitudes towards reducing meat consumption. Data were transcribed and analysed thematically. Three dominant themes emerged: a lack of awareness of the association between meat consumption and climate change, perceptions of personal meat consumption playing a minimal role in the global context of climate change, and resistance to the idea of reducing personal meat consumption. People associated eating meat with pleasure, and described social, personal and cultural values around eating meat. Some people felt they did not need to eat less meat because they had already reduced their consumption or that they only ate small quantities. Scepticism of scientific evidence linking meat and climate change was common. Changing non-food related behaviours was viewed as more acceptable and a greater priority for climate change mitigation. The study highlights the role meat plays in the diet for many people, beyond nutritional needs. If healthy, sustainable dietary habits are to be achieved, cultural, social and personal values around eating meat must be integrated into the development of future dietary recommendations.
Published:
December 31, 2015
Title:
General Mechanisms of Plant Defense and Plant Toxins
Authors:
Mithöfer, Axel; Maffei, Massimo
Abstract:
Long before the appearance of flowering plants, early plants were infected by pathogenic microorganisms and challenged by herbivorous animals. Consequently, plants and animals evolved defenses and counterdefenses from the very beginning. Therefore, to cope with a huge diversity of unfavorable biotic conditions, plants developed several different defense strategies. In particular, defense strategies against feeding arthropods are highly diverse, including constitutive and inducible, direct and indirect defense mechanism. Among all types of defense, chemical defenses based on the synthesis and accumulation of a consistent number of natural bioactive compounds is a very successful and ubiquitously distributed strategy among the plant kingdom. Many of those compounds are toxic; others act as repellents or are attractive cues for organisms belonging to other trophic levels. Often, toxic compounds have specific targets; other compounds exhibit general toxicity. In such cases plants need to protect themselves. Within the plants’ reservoir of chemical defensive compounds, alkaloids, terpenoids, phenolic compounds, and many polypeptides can be found. Not only herbivorous insects but also mammalian organisms including human beings can be targeted by such plant-derived toxins, which will be demonstrated in selected examples.
Published:
December 31, 2015
Title:
Origin, Development, and Evolution of Primate Muscles, with Notes on Human Anatomical Variations and Anomalies
Authors:
Diogo, Rui; Wood, Bernard
Abstract:
This chapter presents a comparative study that focuses on the muscles of the trunk, pelvis, and lower limb. It draws together the broader evolutionary and developmental implications of the study of the musculature of primates. The chapter also discusses in more detail the origin, ontogeny, and evolution of the head, neck, pectoral, and forelimb muscles. Concerning the head and neck muscles, studies using rhombomeric quail-to-chick grafts to investigate the influence of hindbrain segmentation on craniofacial patterning showed that each rhombomeric neural crest cell population remains coherent throughout ontogeny, with rhombomere-specific matching of muscle connective tissue and their attachment sites for most head and neck muscles. Limbs with digits first appeared in aquatic taxa with more than five digits, but the transitions to terrestrial locomotion and to pentadactyly, and then to digit reduction in some clades, are particularly poorly understood.
Published:
December 31, 2015
Title:
Reproductive state and rank influence patterns of meat consumption in wild female chimpanzees (Pan troglodytes schweinfurthii)
Authors:
O'Malley, Robert C.; Stanton, Margaret A.; Gilby, Ian C.; Lonsdorf, Elizabeth V.; Pusey, Anne; Markham, A. Catherine; Murray, Carson M.
Abstract:
An increase in faunivory is a consistent component of human evolutionary models. Animal matter is energy- and nutrient-dense and can provide macronutrients, minerals, and vitamins that are limited or absent in plant foods. For female humans and other omnivorous primates, faunivory may be of particular importance during the costly periods of pregnancy and early lactation. Yet, because animal prey is often monopolizable, access to fauna among group-living primates may be mediated by social factors such as rank. Wild chimpanzees (Pan troglodytes) across Africa habitually consume insects and/or vertebrates. However, no published studies have examined patterns of female chimpanzee faunivory during pregnancy and early lactation relative to non-reproductive periods, or by females of different rank. In this study, we assessed the influence of reproductive state and dominance rank on the consumption of fauna (meat and insects) by female chimpanzees of Gombe National Park, Tanzania. Using observational data collected over 38 years, we tested (a) whether faunivory varied by reproductive state, and (b) if high-ranking females spent more time consuming fauna than lower-ranking females. In single-factor models, pregnant females consumed more meat than lactating and baseline (meaning not pregnant and not in early lactation) females, and high-ranking females consumed more meat than lower-ranking females. A two-factor analysis of a subset of well-sampled females identified an interaction between rank and reproductive state: lower-ranking females consumed more meat during pregnancy than lower-ranking lactating and baseline females did. High-ranking females did not significantly differ in meat consumption between reproductive states. We found no relationships between rank or reproductive state with insectivory. We conclude that, unlike insectivory, meat consumption by female chimpanzees is mediated by both reproductive state and social rank. We outline possible mechanisms for these patterns, relate our findings to meat-eating patterns in women from well-studied hunter-gatherer societies, and discuss potential avenues for future research.
Published:
December 31, 2015
Title:
Ultra-processed foods and added sugars in the US diet: evidence from a nationally representative cross-sectional study
Authors:
Steele, Eurídice Martínez; Baraldi, Larissa Galastri; Louzada, Maria Laura da Costa; Moubarac, Jean-Claude; Mozaffarian, Dariush; Monteiro, Carlos Augusto
Abstract:
Objectives To investigate the contribution of ultra-processed foods to the intake of added sugars in the USA. Ultra-processed foods were defined as industrial formulations which, besides salt, sugar, oils and fats, include substances not used in culinary preparations, in particular additives used to imitate sensorial qualities of minimally processed foods and their culinary preparations. Design Cross-sectional study. Setting National Health and Nutrition Examination Survey 2009–2010. Participants We evaluated 9317 participants aged 1+ years with at least one 24 h dietary recall. Main outcome measures Average dietary content of added sugars and proportion of individuals consuming more than 10% of total energy from added sugars. Data analysis Gaussian and Poisson regressions estimated the association between consumption of ultra-processed foods and intake of added sugars. All models incorporated survey sample weights and adjusted for age, sex, race/ethnicity, family income and educational attainment. Results Ultra-processed foods comprised 57.9% of energy intake, and contributed 89.7% of the energy intake from added sugars. The content of added sugars in ultra-processed foods (21.1% of calories) was eightfold higher than in processed foods (2.4%) and fivefold higher than in unprocessed or minimally processed foods and processed culinary ingredients grouped together (3.7%). Both in unadjusted and adjusted models, each increase of 5 percentage points in proportional energy intake from ultra-processed foods increased the proportional energy intake from added sugars by 1 percentage point. Consumption of added sugars increased linearly across quintiles of ultra-processed food consumption: from 7.5% of total energy in the lowest quintile to 19.5% in the highest. A total of 82.1% of Americans in the highest quintile exceeded the recommended limit of 10% energy from added sugars, compared with 26.4% in the lowest. Conclusions Decreasing the consumption of ultra-processed foods could be an effective way of reducing the excessive intake of added sugars in the USA.
Published:
December 31, 2015
Title:
Stories for change: development of a diabetes digital storytelling intervention for refugees and immigrants to minnesota using qualitative methods
Authors:
Njeru, Jane W.; Patten, Christi A.; Hanza, Marcelo M. K.; Brockman, Tabetha A.; Ridgeway, Jennifer L.; Weis, Jennifer A.; Clark, Matthew M.; Goodson, Miriam; Osman, Ahmed; Porraz-Capetillo, Graciela; Hared, Abdullah; Myers, Allison; Sia, Irene G.; Wieland, Mark L.
Abstract:
Immigrants and refugees are affected by diabetes-related health disparities, with higher rates of incident diabetes and sub-optimal diabetes outcomes. Digital storytelling interventions for chronic diseases, such as diabetes may be especially powerful among immigrants because often limited English proficiency minimizes access to and affects the applicability of the existing health education opportunities. Community-based participatory research (CBPR), whereby community members and academia partner in an equitable relationship through all phases of the research, is an intuitive approach to develop these interventions. The main objective of this study was to develop a diabetes digital storytelling intervention with and for immigrant and refugee populations.
Published:
December 28, 2015
Title:
Omega-3 Fatty Acid Supplementation for 12 Weeks Increases Resting and Exercise Metabolic Rate in Healthy Community-Dwelling Older Females
Authors:
Logan, Samantha L.; Spriet, Lawrence L.
Abstract:
Critical among the changes that occur with aging are decreases in muscle mass and metabolic rate and an increase in fat mass. These changes may predispose older adults to chronic disease and functional impairment; ultimately resulting in a decrease in the quality of life. Research has suggested that long chain omega-3 fatty acids, found predominantly in fatty fish, may assist in reducing these changes. The objective of this study was to evaluate the effect of fish oil (FO) supplementation in a cohort of healthy, community-dwelling older females on 1) metabolic rate and substrate oxidation at rest and during exercise; 2) resting blood pressure and resting and exercise heart rates; 3) body composition; 4) strength and physical function, and; 5) blood measures of insulin, glucose, c-reactive protein, and triglycerides. Twenty-four females (66 ± 1 yr) were recruited and randomly assigned to receive either 3g/d of EPA and DHA or a placebo (PL, olive oil) for 12 wk. Exercise measurements were taken before and after 12 wk of supplementation and resting metabolic measures were made before and at 6 and 12 wk of supplementation. The results demonstrated that FO supplementation significantly increased resting metabolic rate by 14%, energy expenditure during exercise by 10%, and the rate of fat oxidation during rest by 19% and during exercise by 27%. In addition, FO consumption lowered triglyceride levels by 29% and increased lean mass by 4% and functional capacity by 7%, while no changes occurred in the PL group. In conclusion, FO may be a strategy to improve age-related physical and metabolic changes in healthy older females. Trial Registration: ClinicalTrials.gov NCT01734538.
Published:
December 16, 2015
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