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Title:
Associations between Sleep, Cortisol Regulation, and Diet: Possible Implications for the Risk of Alzheimer Disease.
Authors:
Pistollato, Francesca; Sumalla Cano, Sandra; Elio, Inaki; Masias Vergara, Manuel; Giampieri, Francesca; Battino, Maurizio
Abstract:
Accumulation of proteinaceous amyloid beta plaques and tau oligomers may occur several years before the onset of Alzheimer disease (AD). Under normal circumstances, misfolded proteins get cleared by proteasome degradation, autophagy, and the recently discovered brain glymphatic system, an astroglial-mediated interstitial fluid bulk flow. It has been shown that the activity of the glymphatic system is higher during sleep and disengaged or low during wakefulness. As a consequence, poor sleep quality, which is associated with dementia, might negatively affect glymphatic system activity, thus contributing to amyloid accumulation. The diet is another important factor to consider in the regulation of this complex network. Diets characterized by high intakes of refined sugars, salt, animal-derived proteins and fats and by low intakes of fruit and vegetables are associated with a higher risk of AD and can perturb the circadian modulation of cortisol secretion, which is associated with poor sleep quality. For this reason, diets and nutritional interventions aimed at restoring cortisol concentrations may ease sleep disorders and may facilitate brain clearance, consequentially reducing the risk of cognitive impairment and dementia. Here, we describe the associations that exist between sleep, cortisol regulation, and diet and their possible implications for the risk of cognitive impairment and AD.
Published:
2016-07
Title:
Associations of urinary sodium excretion with cardiovascular events in individuals with and without hypertension: a pooled analysis of data from four studies
Authors:
Mente, Andrew; O'Donnell, Martin; Rangarajan, Sumathy; Dagenais, Gilles; Lear, Scott; McQueen, Matthew; Diaz, Rafael; Avezum, Alvaro; Lopez-Jaramillo, Patricio; Lanas, Fernando; Li, Wei; Lu, Yin; Yi, Sun; Rensheng, Lei; Iqbal, Romaina; Mony, Prem; Yusuf, Rita; Yusoff, Khalid; Szuba, Andrzej; Oguz, Aytekin; Rosengren, Annika; Bahonar, Ahmad; Yusufali, Afzalhussein; Schutte, Aletta Elisabeth; Chifamba, Jephat; Mann, Johannes F E; Anand, Sonia S; Teo, Koon; Yusuf, S
Abstract:
Published:
2016-07
Title:
Emerging Evidence for the Importance of Dietary Protein Source on Glucoregulatory Markers and Type 2 Diabetes: Different Effects of Dairy, Meat, Fish, Egg, and Plant Protein Foods. [Review]
Authors:
Comerford, Kevin B.; Pasin, Gonca
Abstract:
Observational studies provide evidence that a higher intake of protein from plant-based foods and certain animal-based foods is associated with a lower risk for type 2 diabetes. However, there are few distinguishable differences between the glucoregulatory qualities of the proteins in plant-based foods, and it is likely their numerous non-protein components (e.g., fibers and phytochemicals) that drive the relationship with type 2 diabetes risk reduction. Conversely, the glucoregulatory qualities of the proteins in animal-based foods are extremely divergent, with a higher intake of certain animal-based protein foods showing negative effects, and others showing neutral or positive effects on type 2 diabetes risk. Among the various types of animal-based protein foods, a higher intake of dairy products (such as milk, yogurt, cheese and whey protein) consistently shows a beneficial relationship with glucose regulation and/or type 2 diabetes risk reduction. Intervention studies provide evidence that dairy proteins have more potent effects on insulin and incretin secretion compared to other commonly consumed animal proteins. In addition to their protein components, such as insulinogenic amino acids and bioactive peptides, dairy products also contain a food matrix rich in calcium, magnesium, potassium, trans-palmitoleic fatty acids, and low-glycemic index sugars-all of which have been shown to have beneficial effects on aspects of glucose control, insulin secretion, insulin sensitivity and/or type 2 diabetes risk. Furthermore, fermentation and fortification of dairy products with probiotics and vitamin D may improve a dairy product's glucoregulatory effects.
Published:
2016-07
Title:
Training in metabolomics research. I. Designing the experiment, collecting and extracting samples and generating metabolomics data
Authors:
Barnes, Stephen; Benton, H. Paul; Casazza, Krista; Cooper, Sara J.; Cui, Xiangqin; Du, Xiuxia; Engler, Jeffrey; Kabarowski, Janusz H.; Li, Shuzhao; Pathmasiri, Wimal; Prasain, Jeevan K.; Renfrow, Matthew B.; Tiwari, Hemant K.
Abstract:
The study of metabolism has had a long history. Metabolomics, a systems biology discipline representing analysis of known and unknown pathways of metabolism, has grown tremendously over the past 20 years. Because of its comprehensive nature, metabolomics requires careful consideration of the question(s) being asked, the scale needed to answer the question(s), collection and storage of the sample specimens, methods for extraction of the metabolites from biological matrices, the analytical method(s) to be employed and the quality control of the analyses, how collected data are correlated, the statistical methods to determine metabolites undergoing significant change, putative identification of metabolites and the use of stable isotopes to aid in verifying metabolite identity and establishing pathway connections and fluxes. The National Institutes of Health Common Fund Metabolomics Program was established in 2012 to stimulate interest in the approaches and technologies of metabolomics. To deliver one of the program’s goals, the University of Alabama at Birmingham has hosted an annual 4-day short course in metabolomics for faculty, postdoctoral fellows and graduate students from national and international institutions. This paper is the first part of a summary of the training materials presented in the course to be used as a resource for all those embarking on metabolomics research.
Published:
2016-07
Title:
Diet low in advanced glycation end products increases insulin sensitivity in healthy overweight individuals: a double-blind, randomized, crossover trial
Authors:
de Courten, Barbora; de Courten, Maximilian Pj; Soldatos, Georgia; Dougherty, Sonia L.; Straznicky, Nora; Schlaich, Markus; Sourris, Karly C.; Chand, Vibhasha; Scheijen, Jean Ljm; Kingwell, Bronwyn A.; Cooper, Mark E.; Schalkwijk, Casper G.; Walker, Karen Z.; Forbes, Josephine M.
Abstract:
BACKGROUND: The consumption of advanced glycation end products (AGEs) has increased because of modern food processing and has been linked to the development of type 2 diabetes in rodents. OBJECTIVE: We determined whether changing dietary AGE intake could modulate insulin sensitivity and secretion in healthy, overweight individuals. DESIGN: We performed a double-blind, randomized, crossover trial of diets in 20 participants [6 women and 14 men; mean ± SD body mass index (in kg/m(2)): 29.8 ± 3.7]. Isoenergetic- and macronutrient-matched diets that were high or low in AGE content were alternately consumed for 2 wk and separated by a 4-wk washout period. At the beginning and end of each dietary period, a hyperinsulinemic-euglycemic clamp and an intravenous glucose tolerance test were performed. Dietary, plasma and urinary AGEs N(€)-(carboxymethyl)lysine (CML), N(€)-(carboxyethyl)lysin (CEL), and methylglyoxal-derived hydroimadazolidine (MG-H1) were measured with the use of mass spectrometry. RESULTS: Participants consumed less CML, CEL, and MG-H1 during the low-AGE dietary period than during the high-AGE period (all P
Published:
2016-06
Title:
Influence of dietary fat and carbohydrates proportions on plasma lipids, glucose control and low-grade inflammation in patients with type 2 diabetes-The TOSCA.IT Study
Authors:
Vitale, M.; Masulli, M.; Rivellese, A. A.; Babini, A. C.; Boemi, M.; Bonora, E.; Buzzetti, R.; Ciano, O.; Cignarelli, M.; Cigolini, M.; Clemente, G.; Citro, G.; Corsi, L.; Dall'Aglio, E.; Del Prato, S.; Di Cianni, G.; Dolci, M. A.; Giordano, C.; Iannarelli, R.; Iovine, C.; Lapolla, A.; Lauro, D.; Leotta, S.; Mazzucchelli, C.; Montani, V.; Perriello, G.; Romano, G.; Romeo, F.; Santarelli, L.; di Cola, R. Schiano; Squatrito, S.; Tonutti, L.; Trevisan, R.; Turco, A. A.; Zamboni, C.; Riccardi, G.; Vaccaro, O.
Abstract:
CONCLUSIONS: In people with type 2 diabetes, variations in the proportion of fat and carbohydrates of the diet, within the relatively narrow ranges recommended by different nutritional guidelines, significantly impact on the metabolic profile and markers of low-grade inflammation. The data support the potential for reducing the intake of fat and added sugars, preferring complex, slowly absorbable, carbohydrates.
Published:
2016-06
Title:
Ketogenic Diet, but Not Polyunsaturated Fatty Acid Diet, Reduces Spontaneous Seizures in Juvenile Rats with Kainic Acid-induced Epilepsy
Authors:
Dustin, Simone M.; Stafstrom, Carl E.
Abstract:
BACKGROUND AND PURPOSE: The high-fat, low-carbohydrate ketogenic diet (KD) is effective in many cases of drug-resistant epilepsy, particularly in children. In the classic KD, fats consist primarily of long-chain saturated triglycerides. Polyunsaturated fatty acids (PUFAs), especially the n-3 type, decrease neuronal excitability and provide neuroprotection; pilot human studies have raised the possibility of using PUFAs to control seizures in patients. METHODS: To determine the relative roles of the KD and PUFAs in an animal model, we induced epilepsy in juvenile rats (P29-35) using intraperitoneal kainic acid (KA). KA caused status epilepticus in all rats. Two days after KA, rats were randomized to one of 4 dietary groups: Control diet; PUFA diet; KD; or KD plus PUFA. All diets were administered isocalorically at 90% of the rat recommended daily calorie requirement. Spontaneous recurrent seizures (SRS) were assessed for 3 months after diet randomization. RESULTS: Rats receiving the KD or KD-PUFA diet had significantly fewer SRS than those receiving the Control diet or PUFA diet. The PUFA diet did not reduce SRS compared to the Control diet. CONCLUSIONS: In the KA epilepsy model, the KD protects against SRS occurrence but dietary enhancement with PUFA does not afford additional protection against spontaneous seizures.
Published:
2016-06
Title:
Nutrient-sensing mTORC1: Integration of metabolic and autophagic signals
Authors:
Tan, Valerie P.; Miyamoto, Shigeki
Abstract:
\textlessh2\textgreaterAbstract\textless/h2\textgreater\textlessp\textgreaterThe ability of adult cardiomyocytes to regenerate is limited, and irreversible loss by cell death plays a crucial role in heart diseases. Autophagy is an evolutionarily conserved cellular catabolic process through which long-lived proteins and damaged organelles are targeted for lysosomal degradation. Autophagy is important in cardiac homeostasis and can serve as a protective mechanism by providing an energy source, especially in the face of sustained starvation. Cellular metabolism is closely associated with cell survival, and recent evidence suggests that metabolic and autophagic signaling pathways exhibit a high degree of crosstalk and are functionally interdependent. In this review, we discuss recent progress in our understanding of regulation of autophagy and its crosstalk with metabolic signaling, with a focus on the nutrient-sensing mTOR complex 1 (mTORC1) pathway.\textless/p\textgreater
Published:
2016-06
Title:
Soluble sortilin is released by activated platelets and its circulating levels are associated with cardiovascular risk factors
Authors:
Ogawa, Kazuyuki; Ueno, Takahiro; Iwasaki, Tadao; Kujiraoka, Takeshi; Ishihara, Mitsuaki; Kunimoto, Satoshi; Takayama, Tadateru; Kanai, Takashi; Hirayama, Atsushi; Hattori, Hiroaki
Abstract:
Published:
2016-06
Title:
The Effect of Meal Frequency on the Fatty Acid Composition of Serum Phospholipids in Patients with Type 2 Diabetes
Authors:
Kahleova, Hana; Malinska, Hana; Kazdova, Ludmila; Belinova, Lenka; Tura, Andrea; Hill, Martin; Pelikanova, Terezie
Abstract:
OBJECTIVE: Fatty acids are important cellular constituents that can affect many metabolic processes relevant for the development of diabetes and its complications. We previously demonstrated a positive effect of eating just 2 meals a day, breakfast and lunch, compared to 6 small meals. The aim of this secondary analysis was to explore the effect of meal frequency on the fatty acid composition of serum phospholipids in subjects with type 2 diabetes (T2D). METHODS: In a randomized, crossover study, we assigned 54 patients with T2D to follow one of 2 regimens of a hypocaloric diet (-500 kcal/day), each for 12 weeks: 6 meals (A6) or 2 meals a day, breakfast and lunch (B2). The diet in both regimens had the same macronutrient and energy content. The fatty acid composition of serum phospholipids was measured at weeks 0, 12, and 24, using gas liquid chromatography. Insulin sensitivity was derived as an oral glucose insulin sensitivity (OGIS) index. RESULTS: Saturated fatty acids (mainly myristic and palmitic acids) decreased (p < 0.001) and n6 polyunsaturated fatty acids increased (p < 0.001) in response to both regimens but more with B2 (p < 0.001 for both). Monounsaturated fatty acids decreased (p < 0.05) and n3 polyunsaturated fatty acids increased (p
Published:
2016-06
Title:
Treatment of Dravet Syndrome
Authors:
Wirrell, Elaine C.
Abstract:
Dravet syndrome is among the most challenging electroclinical syndromes. There is a high likelihood of recurrent status epilepticus; seizures are medically refractory; and patients have multiple co-morbidities, including intellectual disability, behaviour and sleep problems, and crouch gait. Additionally, they are at significant risk of sudden unexplained death. This review will focus predominantly on the prophylactic medical management of seizures, addressing both first-line therapies (valproate and clobazam) as well as second-line (stiripentol, topiramate, ketogenic diet) or later options (levetiracetam, bromides, vagus nerve stimulation). Sodium channel agents-including carbamazepine, oxcarbazepine, phenytoin and lamotrigine-should be avoided, as they typically exacerbate seizures. Several agents in development may show promise, specifically fenfluramine and cannabidiol, but they need further evaluation in randomized, controlled trials. In addition to prophylactic treatment, all patients need home-rescue medication and a status epilepticus protocol that can be carried out in their local hospital. Families must be counselled on non-pharmacologic strategies to reduce seizure risk, including avoidance of triggers that commonly induce seizures (including hyperthermia, flashing lights and patterns). In addition to addressing seizures, holistic care for a patient with Dravet syndrome must involve a multidisciplinary team that includes specialists in physical, occupational and speech therapy, neuropsychology, social work and physical medicine.
Published:
2016-06
Title:
Vegetarian and Omnivorous Nutrition - Comparing Physical Performance
Authors:
Craddock, Joel C.; Probst, Yasmine C.; Peoples, Gregory E.
Abstract:
Humans consuming vegetarian-based diets are observed to have reduced relative risk for many chronic diseases. Similarly, regular physical activity has also been shown to assist in preventing, and reducing the severity of these conditions. Many people, including athletes, acknowledge these findings and are adopting a vegetarian-based diet to improve their health status. Furthermore, athletes are incorporating this approach with the specific aim of optimizing physical performance. To examine the evidence for the relationship between consuming a predominately vegetarian-based diet and improved physical performance, a systematic literature review was performed using the SCOPUS database. No date parameters were set. The keywords vegetarian OR vegan AND sport OR athlete OR training OR performance OR endurance were used to identify relevant literature. Included studies (i) directly compared a vegetarian-based diet to an omnivorous/mixed diet, (ii) directly assessed physical performance, not biomarkers of physical performance, and (iii) did not use supplementation emulating a vegetarian diet. Reference lists were hand searched for additional studies. Seven randomized controlled trials and one cross-sectional study met the inclusion criteria. No distinguished differences between vegetarian-based diets and omnivorous mixed diets were identified when physical performance was compared. Consuming a predominately vegetarian-based diet did not improve nor hinder performance in athletes. However, with only 8 studies identified, with substantial variability among the studies' experimental designs, aims and outcomes, further research is warranted.
Published:
2016-06
Title:
Very low-calorie ketogenic diet may allow restoring response to systemic therapy in relapsing plaque psoriasis
Authors:
Castaldo, Giuseppe; Galdo, Giovanna; Rotondi Aufiero, Felice; Cereda, Emanuele
Abstract:
Psoriasis is a chronic disease associated with overweight/obesity and related cardiometabolic complications. The link between these diseases is likely the inflammatory background associated with adipose tissue, particularly the visceral one. Accordingly, previous studies have demonstrated that in the long-term weight loss may improve the response to systemic therapies. We report a case report of a woman in her 40s suffering from relapsing moderate-to-severe plaque psoriasis and obesity-related metabolic syndrome, in whom adequate response to ongoing treatment with biological therapy (adalimumab) was restored after only 4 weeks of very low-calorie, carbohydrate-free (ketogenic), protein-based diet. Accordingly, through rapid and consistent weight loss, very low calorie ketogenic diet may allow restoring a quick response to systemic therapy in a patient suffering from relapsing psoriasis. This intervention should be considered in overweight/obese patients before the rearrangement of systemic therapy. Nonetheless, studies are required to evaluate whether very low calorie ketogenic diets should be preferred to common low-calorie diets to improve the response to systemic therapy at least in patients with moderate-to-severe psoriasis.
Published:
2016-06
Title:
Alterations in expression of imprinted genes from the H19/IGF2 loci in a multigenerational model of intrauterine growth restriction (IUGR)
Authors:
Gonzalez-Rodriguez, Pablo; Cantu, Jessica; O’Neil, Derek; Seferovic, Maxim D.; Goodspeed, Danielle M.; Suter, Melissa A.; Aagaard, Kjersti M.; O'Neil, Derek
Abstract:
Background: The H19/IGF2 imprinted loci have attracted recent attention because of their role in cellular differentiation and proliferation, heritable gene regulation, and in utero or early postnatal growth and development. Expression from the imprinted H19/IGF2 locus involves a complex interplay of 3 means of epigenetic regulation: proper establishment of DNA methylation, promoter occupancy of CTCF, and expression of microRNA-675. We have demonstrated previously in a multigenerational rat model of intrauterine growth restriction the epigenetic heritability of adult metabolic syndrome in a F2 generation. We have further demonstrated abrogation of the F2 adult metabolic syndrome phenotype with essential nutrient supplementation of intermediates along the 1-carbon pathway and shown that alterations in the metabolome precede the adult onset of metabolic syndrome. The upstream molecular and epigenomic mediators underlying these observations, however, have yet to be elucidated fully.Objective: In the current study, we sought to characterize the impact of the intrauterine growth-restricted lineage and essential nutrient supplementation on both levels and molecular mediators of H19 and IGF2 gene expression in the F2 generation.Study Design: F2 intrauterine growth-restricted and sham lineages were obtained by exposing P1 (grandmaternal) pregnant dams to bilateral uterine artery ligation or sham surgery at gestational day 19.5. F1 pups were allocated to the essential nutrient supplemented or control diet at postnatal day 21, and bred at 6-7 weeks of age. Hepatic tissues from the resultant F2 offspring at birth and at weaning (day 21) were obtained. Bisulfite modification and sequencing was employed for methylation analysis. H19 and IGF2 expression was measured by quantitative polymerase chain reaction. Promoter occupancy was quantified by the use of chromatin immunoprecipitation, or ChIP, against CTCF insulator proteins.Results: Growth-restricted F2 on control diet demonstrated significant down-regulation in H19 expression compared with sham lineage (0.7831 vs 1.287; P .05). Conversely, Igf2 was up-regulated by essential nutrient supplemented diet on the sham lineage (2.0 fold, P = .01), an effect that was not observed in the growth restricted offspring. A significant differential methylation was observed in the promoter region of region H19 among the intrauterine growth-restricted lineage (18% vs 25%; P < .05) on a control diet, whereas the essential nutrient supplemented diet was alternately associated with hypermethylation in both lineages (sham: 50%; intrauterine growth restriction: 84%, P < .05). Consistent with essential nutrient supplementation impacting the epigenome, a decrease of CTCF promoter occupancy was observed in CTCF4 of the growth restricted lineage (2.45% vs 0.56%; P
Published:
2016-05
Title:
Barriers and facilitators to reaching a diagnosis of PNES from the patients’ perspective: Preliminary findings
Authors:
Pretorius, Chrisma
Abstract:
Purpose: This qualitative study aimed at examining the subjective experiences of patients during the complicated and often prolonged diagnostic process of psychogenic non-epileptic seizures (PNES). Methods: Thematic analyses were used to explore the semi-structured interviews that were conducted with ten individuals who have been diagnosed with PNES. Results: Six main themes, namely inexpert healthcare providers, limited medical insurance and loss of independence were identified as barriers, while social support, comprehensive medical insurance and knowledgeable healthcare providers were identified as facilitators through the process of thematic analysis. Conclusions: The patients’ perspectives revealed that an earlier diagnosis of PNES is essential to address the loss of independence and limit inappropriate and potentially harmful treatment as well as the costly burden of this condition on both the patient and the healthcare system. It was evident in this study that healthcare providers play an essential role in the subjective experiences of these individuals during the diagnostic process. The implementation of continuous education programmes for healthcare providers in particular could contribute positively to the diagnostic process of PNES for patients.
Published:
2016-05
Title:
Dark chocolate exacerbates acne
Authors:
Vongraviopap, Saivaree; Asawanonda, Pravit
Abstract:
The effects of chocolate on acne exacerbations have recently been reevaluated. For so many years, it was thought that it had no role in worsening acne. To investigate whether 99% dark chocolate, when consumed in regular daily amounts, would cause acne to worsen in acne-prone male subjects, twenty-five acne prone male subjects were asked to consume 25 g of 99% dark chocolate daily for 4 weeks. Assessments which included Leeds revised acne scores as well as lesion counts took place weekly. Food frequency questionnaire was used, and daily activities were recorded. Statistically significant changes of acne scores and numbers of comedones and inflammatory papules were detected as early as 2 weeks into the study. At 4 weeks, the changes remained statistically significant compared to baseline. Dark chocolate when consumed in normal amounts for 4 weeks can exacerbate acne in male subjects with acne-prone skin.
Published:
2016-05
Title:
Dark chocolate exacerbates acne
Authors:
Vongraviopap, Saivaree; Asawanonda, Pravit
Abstract:
The effects of chocolate on acne exacerbations have recently been reevaluated. For so many years, it was thought that it had no role in worsening acne. To investigate whether 99% dark chocolate, when consumed in regular daily amounts, would cause acne to worsen in acne-prone male subjects, twenty-five acne prone male subjects were asked to consume 25 g of 99% dark chocolate daily for 4 weeks. Assessments which included Leeds revised acne scores as well as lesion counts took place weekly. Food frequency questionnaire was used, and daily activities were recorded. Statistically significant changes of acne scores and numbers of comedones and inflammatory papules were detected as early as 2 weeks into the study. At 4 weeks, the changes remained statistically significant compared to baseline. Dark chocolate when consumed in normal amounts for 4 weeks can exacerbate acne in male subjects with acne-prone skin.
Published:
2016-05
Title:
Diffusion-weighted MRI for early detection and characterization of prostate cancer in the transgenic adenocarcinoma of the mouse prostate model
Authors:
Hill, Deborah K.; Kim, Eugene; Teruel, Jose R.; Jamin, Yann; Widerøe, Marius; Søgaard, Caroline D.; Størkersen, Øystein; Rodrigues, Daniel N.; Heindl, Andreas; Yuan, Yinyin; Bathen, Tone F.; Moestue, Siver A.
Abstract:
PURPOSE: To improve early diagnosis of prostate cancer to aid clinical decision-making. Diffusion-weighted magnetic resonance imaging (DW-MRI) is sensitive to water diffusion throughout tissues, which correlates with Gleason score, a histological measure of prostate cancer aggressiveness. In this study the ability of DW-MRI to detect prostate cancer onset and development was evaluated in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. MATERIALS AND METHODS: T2 -weighted and DW-MRI were acquired using a 7T MR scanner, 200 mm bore diameter; 10 TRAMP and 6 C57BL/6 control mice were scanned every 4 weeks from 8 weeks of age until sacrifice at 28-30 weeks. After sacrifice, the genitourinary tract was excised and sectioned for histological analysis. Histology slides registered with DW-MR images allowed for validation of DW-MR images and the apparent diffusion coefficient (ADC) as tools for cancer detection and disease stratification. An automated early assessment tool based on ADC threshold values was developed to aid cancer detection and progression monitoring. RESULTS: The ADC differentiated between control prostate ((1.86 ± 0.20) × 10(-3) mm(2) /s) and normal TRAMP prostate ((1.38 ± 0.10) × 10(-3) mm(2) /s) (P = 0.0001), between TRAMP prostate and well-differentiated cancer ((0.93 ± 0.18) × 10(-3) mm(2) /s) (P = 0.0006), and between well-differentiated cancer and poorly differentiated cancer ((0.63 ± 0.06) × 10(-3) mm(2) /s) (P = 0.02). CONCLUSION: DW-MRI is a tool for early detection of cancer, and discrimination between cancer stages in the TRAMP model. The incorporation of DW-MRI-based prostate cancer stratification and monitoring could increase the accuracy of preclinical trials using TRAMP mice.
Published:
2016-05
Title:
Lauren classification and individualized chemotherapy in gastric cancer
Authors:
MA, JUNLI; SHEN, HONG; KAPESA, LINDA; ZENG, SHAN
Abstract:
Gastric cancer is one of the most common malignancies worldwide. During the last 50 years, the histological classification of gastric carcinoma has been largely based on Lauren's criteria, in which gastric cancer is classified into two major histological subtypes, namely intestinal type and diffuse type adenocarcinoma. This classification was introduced in 1965, and remains currently widely accepted and employed, since it constitutes a simple and robust classification approach. The two histological subtypes of gastric cancer proposed by the Lauren classification exhibit a number of distinct clinical and molecular characteristics, including histogenesis, cell differentiation, epidemiology, etiology, carcinogenesis, biological behaviors and prognosis. Gastric cancer exhibits varied sensitivity to chemotherapy drugs and significant heterogeneity; therefore, the disease may be a target for individualized therapy. The Lauren classification may provide the basis for individualized treatment for advanced gastric cancer, which is increasingly gaining attention in the scientific field. However, few studies have investigated individualized treatment that is guided by pathological classification. The aim of the current review is to analyze the two major histological subtypes of gastric cancer, as proposed by the Lauren classification, and to discuss the implications of this for personalized chemotherapy.
Published:
2016-05
Title:
Medium-chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte-neuron lactate and ketone body shuttle systems
Authors:
Thevenet, Jonathan; De Marchi, Umberto; Domingo, Jaime Santo; Christinat, Nicolas; Bultot, Laurent; Lefebvre, Gregory; Sakamoto, Kei; Descombes, Patrick; Masoodi, Mojgan; Wiederkehr, Andreas
Abstract:
Medium-chain triglycerides have been used as part of a ketogenic diet effective in reducing epileptic episodes. The health benefits of the derived medium-chain fatty acids (MCFAs) are thought to result from the stimulation of liver ketogenesis providing fuel for thebrain.We tested whether MCFAs have direct effects on energy metabolism in induced pluripotent stem cell-derived human astrocytes and neurons. Using single-cell imaging, we observed an acute pronounced reduction of the mitochondrial electrical potential and a concomitant drop of the NAD(P)H signal in astrocytes, but not in neurons. Despite the observed effects on mitochondrial function, MCFAs did not lower intracellular ATP levels or activate the energy sensor AMP-activated protein kinase. ATP concentrations in astrocytes were unaltered, even when blocking the respiratory chain, suggesting compensation through accelerated glycolysis. The MCFA decanoic acid (300 μM) promoted glycolysis and augmented lactate formation by 49.6%. The shorter fatty acid octanoic acid (300 μM) did not affect glycolysis but increased the rates of astrocyte ketogenesis 2.17-fold compared with that of control cells. MCFAs may have brain health benefits through the modulation of astrocyte metabolism leading to activation of shuttle systems that provide fuel to neighboring neurons in the form of lactate and ketone bodies.
Published:
2016-05
Title:
Coconut oil consumption and cardiovascular risk factors in humans. [Review]
Authors:
Eyres, Laurence; Eyres, Michael F.; Chisholm, Alexandra; Brown, Rachel C.
Abstract:
Coconut oil is being heavily promoted as a healthy oil, with benefits that include support of heart health. To assess the merits of this claim, the literature on the effect of coconut consumption on cardiovascular risk factors and outcomes in humans was reviewed. Twenty-one research papers were identified for inclusion in the review: 8 clinical trials and 13 observational studies. The majority examined the effect of coconut oil or coconut products on serum lipid profiles. Coconut oil generally raised total and low-density lipoprotein cholesterol to a greater extent than cis unsaturated plant oils, but to a lesser extent than butter. The effect of coconut consumption on the ratio of total cholesterol to high-density lipoprotein cholesterol was often not examined. Observational evidence suggests that consumption of coconut flesh or squeezed coconut in the context of traditional dietary patterns does not lead to adverse cardiovascular outcomes. However, due to large differences in dietary and lifestyle patterns, these findings cannot be applied to a typical Western diet. Overall, the weight of the evidence from intervention studies to date suggests that replacing coconut oil with cis unsaturated fats would alter blood lipid profiles in a manner consistent with a reduction in risk factors for cardiovascular disease. Copyright © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Published:
2016-04
Title:
Dietary Betaine Supplementation Increases Fgf21 Levels to Improve Glucose Homeostasis and Reduce Hepatic Lipid Accumulation in Mice
Authors:
Ejaz, Asma; Martinez-Guino, Laura; Goldfine, Allison B.; Ribas-Aulinas, Francesc; De Nigris, Valeria; Ribó, Sílvia; Gonzalez-Franquesa, Alba; Garcia-Roves, Pablo M.; Li, Elizabeth; Dreyfuss, Jonathan M.; Gall, Walt; Kim, Jason K.; Bottiglieri, Teodoro; Villarroya, Francesc; Gerszten, Robert E.; Patti, Mary-Elizabeth; Lerin, Carles
Abstract:
Identifying markers of human insulin resistance may permit development of new approaches for treatment and prevention of type 2 diabetes. To this end, we analyzed the fasting plasma metabolome in metabolically characterized human volunteers across a spectrum of insulin resistance. We demonstrate that plasma betaine levels are reduced in insulin-resistant humans and correlate closely with insulin sensitivity. Moreover, betaine administration to mice with diet-induced obesity prevents the development of impaired glucose homeostasis, reduces hepatic lipid accumulation, increases white adipose oxidative capacity, and enhances whole-body energy expenditure. In parallel with these beneficial metabolic effects, betaine supplementation robustly increased hepatic and circulating fibroblast growth factor (Fgf)21 levels. Betaine administration failed to improve glucose homeostasis and liver fat content in Fgf21(-/-) mice, demonstrating that Fgf21 is necessary for betaine's beneficial effects. Together, these data indicate that dietary betaine increases Fgf21 levels to improve metabolic health in mice and suggest that betaine supplementation merits further investigation as a supplement for treatment or prevention of type 2 diabetes in humans.
Published:
2016-04
Title:
FT3/FT4 ratio predicts non-alcoholic fatty liver disease independent of metabolic parameters in patients with euthyroidism and hypothyroidism
Authors:
Gökmen, Fatma Yahyaoğlu; Ahbab, Süleyman; Ataoğlu, Hayriye Esra; Türker, Betül Çavuşoğlu; Çetin, Faik; Türker, Fatih; Mamaç, Rabia Yahyaoğlu; Yenigün, Mustafa
Abstract:
OBJECTIVE: This study was performed to evaluate the effects of metabolic parameters and thyroid dysfunction on the development of non-alcoholic fatty liver disease (NAFLD). METHODS: The current study evaluated a total of 115 patients, 75 female and 40 male. Physical examination and anthropometric measurements were applied to all participants. Hypothyroidism was considered at a thyroid stimulating hormone level ≥ 4.1 mIU/L. Patients with euthyroidism and patients with hypothyroidism were compared. Abdominal ultrasonography was used to diagnose non-alcoholic fatty liver disease. The participants were further compared with regard to the presence of non-alcoholic fatty liver disease. Logistic regression modeling was performed to identify the relationship between non-alcoholic fatty liver disease and independent variables, such as metabolic parameters and insulin resistance. RESULTS: Non-alcoholic fatty liver disease was identified in 69 patients. The mean waist circumference, body mass index, fasting plasma insulin, HOMA-IR (p
Published:
2016-04
Title:
Mechanisms underlying glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 secretion
Authors:
Reimann, Frank; Gribble, Fiona M.
Abstract:
The incretin hormones, glucose-dependent insulinotropic peptide and glucagon-like peptide-1, are secreted from intestinal K- and L cells, respectively, with the former being most abundant in the proximal small intestine, whereas the latter increase in number towards the distal gut. Although an overlap between K- and L cells can be observed immunohistochemically or in murine models expressing fluorescent markers under the control of the two hormone promoters, the majority (>80%) of labeled cells seems to produce only one of these hormones. Transcriptomic analysis showed a close relationship between small intestinal K- and L cells, and glucose sensing mechanisms appear similar in both cell types with a predominant role of electrogenic glucose uptake through sodium-coupled glucose transporter 1. Similarly, both cell types produce the long-chain fatty acid sensing G-protein-coupled receptors, FFAR1 (GPR40) and FFAR4 (GPR120), but differ in the expression/functionality of other lipid sensing receptors. GPR119 and FFAR2/3, for example, have clearly documented roles in glucagon-like peptide-1 secretion, whereas agonists for the endocannabinoid receptor type 1 have been found to show largely selective inhibition of glucose-dependent insulinotropic peptide secretion. In conclusion, although K- and L cell populations overlap and share key molecular nutrient-sensing mechanisms, subtle differences between the responsiveness of the different cell types might be exploited to differentially modulate glucose-dependent insulinotropic peptide or glucagon-like peptide-1 secretion.
Published:
2016-04
Title:
Multiplatform metabolomic fingerprinting as a tool for understanding hypercholesterolemia in Wistar rats
Authors:
González-Peña, Diana; Dudzik, Danuta; Colina-Coca, Clara; Ancos, Begoña; García, Antonia; Barbas, Coral; Sánchez-Moreno, Concepción
Abstract:
Purpose: The aim was to investigate the impact of hypercholesterolemic diet on the metabolome of male Wistar rats by a multiplatform metabolomic fingerprinting. Methods: Male Wistar rats were fed with two different diets [control (C) and high-cholesterol diet (HC)-containing 2 % cholesterol and 0.5 % cholic acid]. After 7 weeks of experimental feeding, the rats were euthanized for blood collection and plasma recovery. The metabolite fingerprint was then achieved by applying a multiplatform comprising LC-MS, GC-MS and CE-MS. Results: Multivariate statistical analysis showed a clear separation between the C and HC groups. Individual differences in metabolites were evaluated using univariate statistical analysis, and multiple metabolites were identified and confirmed in the plasma. A global profiling integrates for the first time pathways affected by high-cholesterol diet intake and allowed us to elucidate some of the associated alterations underlying the hypercholesterolemia event in Wistar rats. Conclusions: HC feeding stimulated the alteration of multiple pathways in Wistar rats, warning of the risk of developing important diseases, which can be modulated by the diet. Further studies are required to investigate the possibilities to revert or ameliorate the negative effects triggered by HC intake.
Published:
2016-04
Title:
Pyranocoumarin Tissue Distribution, Plasma Metabolome and Prostate Transcriptome Impacts of Sub-Chronic Exposure to Korean Angelica Supplement in Mice
Authors:
Zhang, Jinhui; Li, Li; Tang, Suni; Zhang, Yong; Markiewski, Maciej; Xing, Chengguo; Jiang, Cheng; Lü, Junxuan
Abstract:
Herbal products containing Korean Angelica gigas Nakai (AGN) root extract are marketed as dietary supplements for memory enhancement, pain killing, and female menopausal symptom relief. We have shown the anticancer activities of AGN supplements in mouse models. To facilitate human anticancer translational research, we characterized the tissue distribution of AGN marker pyranocoumarin compounds decursin (D) and decursinol angelate (DA) (% in AGN) and their metabolite decursinol (DOH), assessed the safety of sub-chronic AGN dietary exposure in mice, and explored its impact on plasma aqueous metabolites and the prostate transcriptome. The data show that after a gavage dose, plasma contained readily detectable DOH, but little D and DA, mirroring patterns in the liver. Extra-hepatic tissues retained greater levels of DA and D than the liver did. For sub-chronic exposures, male mice were provided ad libitum AIN93M-pellet diets with 0.5 and 1% AGN for six weeks. No adverse effects were observed on the plasma biochemistry markers of liver and kidney integrity in spite of their enlargement. Histopathological examinations of the liver, kidney and other visceral organs did not reveal tissue abnormalities. Metabolomic assessment of plasma from mice fed the 1%-AGN diet suggested metabolic shifts of key amino acids especially in the methionine-cysteine cycle, purine cycle, and glycolysis-citrate cycle. Prostate transcriptomic profiling identified gene signature changes in the metabolisms of drugs, lipids and cellular energetics, neuro-muscular features, immunity and inflammation, and tumor suppressor/oncogene balance. The safety profile was corroborated with a daily injection of AGN extract (100-300mg/kg) for four weeks, which resulted in much greater systemic pyranocoumarin exposure than the dietary route did.
Published:
2016-04
Title:
Severe Hypertriglyceridemia in Glut1D on Ketogenic Diet
Authors:
Klepper, Joerg; Leiendecker, Baerbel; Heussinger, Nicole; Lausch, Ekkehart; Bosch, Friedrich
Abstract:
High-fat ketogenic diets are the only treatment available for Glut1 deficiency (Glut1D). Here, we describe an 8-year-old girl with classical Glut1D responsive to a 3:1 ketogenic diet and ethosuximide. After 3 years on the diet a gradual increase of blood lipids was followed by rapid, severe asymptomatic hypertriglyceridemia (1,910 mg/dL). Serum lipid apheresis was required to determine liver, renal, and pancreatic function. A combination of medium chain triglyceride-oil and a reduction of the ketogenic diet to 1:1 ratio normalized triglyceride levels within days but triggered severe myoclonic seizures requiring comedication with sultiam. Severe hypertriglyceridemia in children with Glut1D on ketogenic diets may be underdiagnosed and harmful. In contrast to congenital hypertriglyceridemias, children with Glut1D may be treated effectively by dietary adjustments alone.
Published:
2016-04
Title:
The "handling" of power in the physician-patient encounter: Perceptions from experienced physicians
Authors:
Nimmon, Laura; Stenfors-Hayes, Terese
Abstract:
Background: Modern healthcare is burgeoning with patient centered rhetoric where physicians "share power" equally in their interactions with patients. However, how physicians actually conceptualize and manage their power when interacting with patients remains unexamined in the literature. This study explored how power is perceived and exerted in the physician-patient encounter from the perspective of experienced physicians. It is necessary to examine physicians' awareness of power in the context of modern healthcare that espouses values of dialogic, egalitarian, patient centered care. Methods: Thirty physicians with a minimum five years' experience practicing medicine in the disciplines of Internal Medicine, Surgery, Pediatrics, Psychiatry and Family Medicine were recruited. The authors analyzed semi-structured interview data using LeCompte and Schensul's three stage process: Item analysis, Pattern analysis, and Structural analysis. Theoretical notions from Bourdieu's social theory served as analytic tools for achieving an understanding of physicians' perceptions of power in their interactions with patients. Results: The analysis of data highlighted a range of descriptions and interpretations of relational power. Physicians' responses fell under three broad categories: (1) Perceptions of holding and managing power, (2) Perceptions of power as waning, and (3) Perceptions of power as non-existent or irrelevant. Conclusions: Although the "sharing of power" is an overarching goal of modern patient-centered healthcare, this study highlights how this concept does not fully capture the complex ways experienced physicians perceive, invoke, and redress power in the clinical encounter. Based on the insights, the authors suggest that physicians learn to enact ethical patient-centered therapeutic communication through reflective, effective, and professional use of power in clinical encounters.
Published:
2016-04
Title:
The evolution of diabetic ketoacidosis: An update of its etiology, pathogenesis and management
Authors:
Nyenwe, Ebenezer A.; Kitabchi, Abbas E.
Abstract:
The prognosis of diabetic ketoacidosis has undergone incredibly remarkable evolution since the discovery of insulin nearly a century ago. The incidence and economic burden of diabetic ketoacidosis have continued to rise but its mortality has decreased to less than 1% in good centers. Improved outcome is attributable to a better understanding of the pathophysiology of the disease and widespread application of treatment guidelines. In this review, we present the changes that have occurred over the years, highlighting the evidence behind the recommendations that have improved outcome. We begin with a discussion of the precipitants and pathogenesis of DKA as a prelude to understanding the rationale for the recommendations. A brief review of ketosis-prone type 2 diabetes, an update relating to the diagnosis of DKA and a future perspective are also provided.
Published:
2016-04
Title:
Throwing, the Shoulder, and Human Evolution
Authors:
Kuhn, John E.
Abstract:
Throwing with accuracy and speed is a skill unique to humans. Throwing has many advantages and the ability to throw has likely been promoted through natural selection in the evolution of humans. There are many unsolved questions regarding the anatomy of the human shoulder. The purpose of this article is to review many of these mysteries and propose that the answer to these questions can be understood if one views the shoulder as a joint that has evolved to throw.
Published:
2016-04
Title:
Throwing, the Shoulder, and Human Evolution
Authors:
Kuhn, John E.
Abstract:
Throwing with accuracy and speed is a skill unique to humans. Throwing has many advantages and the ability to throw has likely been promoted through natural selection in the evolution of humans. There are many unsolved questions regarding the anatomy of the human shoulder. The purpose of this article is to review many of these mysteries and propose that the answer to these questions can be understood if one views the shoulder as a joint that has evolved to throw.
Published:
2016-04
Title:
Twin metabolomics: the key to unlocking complex phenotypes in nutrition research
Authors:
Barron, Rebecca; Bermingham, Kate; Brennan, Lorraine; Gibney, Eileen R.; Gibney, Michael J.; Ryan, Miriam F.; O’Sullivan, Aifric
Abstract:
Twin studies are a valuable resource for studying phenotypes and their underlying biology. Heritability estimates based on the classic twin model show that genes influence human traits including health, diet, and food choice. Metabolomics is a promising tool in nutrition and health research where complex metabolite profiles reflect the metabolic effects of foods and diets as well as the biological pathways associated with diet-related diseases. In recent years, publications arising from twin research have incorporated metabolomic analysis, providing insights into genetic and environmental influences on metabolomic profiles. This article reviews the application of metabolomics in twin research with a particular focus on nutrition and diet-related diseases. The review begins by describing the classic twin study design, followed by a look at its application in nutrition research. Indeed, there is clear evidence for a genetic influence on dietary intake, regardless of the outcome measure: energy, macronutrients, dietary patterns, or food choice. The latter part of the review introduces metabolomic research showing how twin studies can separate aspects of the metabolome that are strongly influenced by genetics vs those that are more influenced by environment. The combination of metabolomics and twin research brings the promise of untangling gene-environment effects on complex phenotypes such as the metabolome, obesity, and diet-related diseases. For example, metabolomics is used in nutrition research to identify metabolites associated with particular dietary patterns. When combined within a twin study design, heritability of metabolite–dietary pattern associations can be established allowing further insight into complex gene-environment interactions that shape individual metabolomes.
Published:
2016-04
Title:
Vulnerability to the Irrelevant Sound Effect in Adult ADHD
Authors:
Pelletier, Marie-France; Hodgetts, Helen M.; Lafleur, Martin F.; Vincent, Annick; Tremblay, Sébastien
Abstract:
OBJECTIVE: An ecologically valid adaptation of the irrelevant sound effect paradigm was employed to examine the relative roles of short-term memory, selective attention, and sustained attention in ADHD. METHOD: In all, 32 adults with ADHD and 32 control participants completed a serial recall task in silence or while ignoring irrelevant background sound. RESULTS: Serial recall performance in adults with ADHD was reduced relative to controls in both conditions. The degree of interference due to irrelevant sound was greater for adults with ADHD. Furthermore, a positive correlation was observed between task performance under conditions of irrelevant sound and the extent of attentional problems reported by patients on a clinical symptom scale. CONCLUSION: The results demonstrate that adults with ADHD exhibit impaired short-term memory and a low resistance to distraction; however, their capacity for sustained attention is preserved as the impact of irrelevant sound diminished over the course of the task.
Published:
2016-04
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