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Title:
Orthorexic and restrained eating behaviour in vegans, vegetarians, and individuals on a diet
Authors:
Barthels, Friederike; Meyer, Frank; Pietrowsky, Reinhard
Abstract:
PURPOSE: Orthorexic eating behaviour, restrained eating, and veganism/vegetarianism are food selection strategies sharing several characteristics. Since there are no studies investigating their interrelationships, aim of the present study was to analyse orthorexic and restrained eating behaviour in (1) a sample of vegans and vegetarians and (2) a sample of individuals on a diet to lose weight. METHOD: Division of samples according to pre-defined criteria in (1) vegans (n = 114), vegetarians (n = 63), individuals with rare meat consumption (n = 83) and individuals with frequent meat consumption (n = 91) and in (2) participants on a diet with dietary change (n = 104), without dietary change (n = 37) and a control group of individuals not on a diet (n = 258). Orthorexic eating behaviour was assessed with the Düsseldorfer Orthorexie Skala and restrained eating was assessed with the Restraint Eating Scale. RESULTS: Vegans and vegetarians do not differ in orthorexic eating behaviour, but both groups score higher in orthorexic eating behaviour than individuals consuming red meat. There are no differences regarding restrained eating. Individuals on a diet with dietary change score higher in both orthorexic and restrained eating, than individuals without dietary change and individuals not on a diet. CONCLUSIONS: Individuals who restrict their eating behaviour, either predominantly due to ethical reasons or with the intention to lose weight, display more orthorexic eating behaviour than individuals not limiting their food consumption. Further research is needed to investigate whether veganism, vegetarianism, or frequent dieting behaviour serve as risk factors for orthorexia. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.
Published:
2018-04
Title:
A defined, plant-based diet utilized in an outpatient cardiovascular clinic effectively treats hypercholesterolemia and hypertension and reduces medications
Authors:
Najjar, Rami S.; Moore, Carolyn E.; Montgomery, Baxter D.
Abstract:
BACKGROUND: Cardiovascular disease (CVD) is a major economic burden in the United States. CVD risk factors, particularly hypertension and hypercholesterolemia, are typically treated with drug therapy. Five-year efficacy of such drugs to prevent CVD is estimated to be 5%. Plant-based diets have emerged as effective mitigators of these risk factors. HYPOTHESIS: The implementation of a defined, plant-based diet for 4 weeks in an outpatient clinical setting may mitigate CVD risk factors and reduce patient drug burden. METHODS: Participants consumed a plant-based diet consisting of foods prepared in a defined method in accordance with a food-classification system. Participants consumed raw fruits, vegetables, seeds, and avocado. All animal products were excluded from the diet. Participant anthropometric and hemodynamic data were obtained weekly for 4 weeks. Laboratory biomarkers were collected at baseline and at 4 weeks. Medication needs were assessed weekly. Data were analyzed using paired-samples t tests and 1-way repeated-measures ANOVA. RESULTS: Significant reductions were observed for systolic (-16.6 mmHg) and diastolic (-9.1 mmHg) blood pressure (P < 0.0005), serum lipids (P ≤ 0.008), and total medication usage (P < 0.0005). Other CVD risk factors, including weight (P < 0.0005), waist circumference (P < 0.0005), heart rate (P = 0.018), insulin (P
Published:
2018-03
Title:
Acetyl-L-Carnitine Supplementation and the Treatment of Depressive Symptoms: A Systematic Review and Meta-Analysis.
Authors:
Veronese, Nicola; Stubbs, Brendon; Solmi, Marco; Ajnakina, Olesya; Carvalho, Andre F.; Maggi, Stefania
Abstract:
OBJECTIVE: Deficiency of acetyl-L-carnitine (ALC) seems to play a role in the risk of developing depression, indicating a dysregulation of fatty acid transport across the inner membrane of mitochondria. However, data about ALC supplementation in humans are limited. We thus conducted a systematic review and meta-analysis investigating the effect of ALC on depressive symptoms across randomized controlled trials (RCTs). METHODS: A literature search in major databases, without language restriction, was undertaken from inception until 30 December 2016. Eligible studies were RCTs of ALC alone or in combination with antidepressant medications, with a control group taking placebo/no intervention or antidepressants. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were used for summarizing outcomes with a random-effect model. RESULTS: Twelve RCTs (11 of which were ALC monotherapy) with a total of 791 participants (mean age = 54 years, % female = 65%) were included. Pooled data across nine RCTs (231 treated with ALC versus 216 treated with placebo and 20 no intervention) showed that ALC significantly reduced depressive symptoms (SMD = -1.10, 95% CI = -1.65 to -0.56, I = 86%). In three RCTs comparing ALC versus antidepressants (162 for each group), ALC demonstrated similar effectiveness compared with established antidepressants in reducing depressive symptoms (SMD = 0.06, 95% CI = -0.22 to 0.34, I = 31%). In these latter RCTs, the incidence of adverse effects was significantly lower in the ALC group than in the antidepressant group. Subgroup analyses suggested that ALC was most efficacious in older adults. CONCLUSIONS: ALC supplementation significantly decreases depressive symptoms compared with placebo/no intervention, while offering a comparable effect with that of established antidepressant agents with fewer adverse effects. Future large scale trials are required to confirm/refute these findings.
Published:
2018-03
Title:
Common and specific genes and peripheral biomarkers in children and adults with Attention-Deficit/Hyperactivity Disorder
Authors:
Bonvicini, Cristian; Faraone, Stephen V.; Scassellati, Catia
Abstract:
Objectives Elucidating the biological mechanisms involved in Attention-deficit/hyperactivity disorder (ADHD) has been challenging. Relatively unexplored is the fact that these mechanisms can differ with age. Methods We present an overview on the major differences between children and adults with ADHD, describing several studies from genomics to metabolomics performed in ADHD children and in adults. A systematic search (up until February, 2016) was conducted. Results From a PRISMA flow-chart, a total of eligibility 350 studies from genomics and metabolomics were found for cADHD and 91 for aADHD. For children, associations were found for genes belonging to dopaminergic (SLC6A3, DRD4, MAOA) and neurodevelopmental (LPHN3, DIRAS2) systems and OPRM1 (Yates Corrected p=0.016; OR=2.27 95%CI:1.15–4.47). Studies of adults have implicated circadian rhythms genes, HTR2A, MAOB and a more generic neurodevelopmental/neurite outgrowth network (BCHE, SNAP25, BAIAP2, NOS1/NO, KCNIP4, SPOCK3; Yates Corrected p=0.007; OR= 3.30 95%CI:1.33–8.29). In common among cADHD and aADHD, the most significant findings are for oxidative stress proteins (MAD, SOD, PON1, ARES, TOS, TAS, OSI), and, in the second level, DISC1, DBH, DDC, microRNA and adiponectin. Conclusions Through a convergent functional genomics, this review contributes to clarify which genetic/biological mechanisms differ with age. The effects of some genes do not change throughout lifetime, whereas others are linked to age specific stages. Additional research and further studies are needed to generate firmer conclusions that might someday be useful for predicting the remission and persistence of the disorder. Although the limitations, some of these genes/proteins could be potential useful biomarkers to discriminate cADHD versus aADHD.
Published:
2018-03
Title:
Dietary intake and biomarker status of folate in Swedish adults
Authors:
Öhrvik, Veronica; Lemming, Eva Warensjö; Nälsén, Cecilia; Becker, Wulf; Ridefelt, Peter; Lindroos, Anna Karin
Abstract:
Purpose: National data on folate status are missing in Sweden, and regional data indicate folate insufficiency in up to more than 25% of the study populations. The objectives were to determine folate intake and status in the adult Swedish population as well as identifying dietary patterns associated with beneficial folate status.Methods: Folate intake was estimated using a web-based 4-d food record in adults aged 18-80 years (n = 1797). Folate status was measured as erythrocyte (n = 282) and plasma folate concentrations (n = 294). Factor analysis was used to derive a dietary pattern associated with a higher folate status.Results: Median folate intake was 246 µg/day (Q1 = 196, Q3 = 304, n = 1797) and for women of reproductive age 227 µg/day (Q1 = 181, Q3 = 282, n = 450). As dietary folate equivalents (DFE), median intake was 257 µg/day (Q1 = 201, Q3 = 323) and for women of reproductive age 239 µg/day (Q1 = 185, Q3 = 300). Low blood folate concentrations were found in 2% (erythrocyte concentrations <317 nmol/L) and 4% (plasma concentrations
Published:
2018-03
Title:
Generic Meal Patterns Identified by Latent Class Analysis: Insights from NANS (National Adult Nutrition Survey)
Authors:
Uzhova, Irina; Woolhead, Clara; Timon, Claire M.; O'Sullivan, Aifric; Brennan, Lorraine; Penalvo, Jose L.; Gibney, Eileen R.
Abstract:
Nutritional data reduction methods are widely applied in nutrition epidemiology in order to classify individuals into meaningful groups with similar dietary patterns. To date, none of the existing studies have applied latent class analysis to examine dietary patterns which include meal types consumed throughout a day. We investigated main meal patterns followed on weekend and weekdays, and evaluated their associations with cardio-metabolic biomarkers. The analyses were performed within the NANS (National Adult Nutrition Survey) a cross-sectional national food consumption survey of 1500 nationally representative Irish adults. A total number of seven dietary patterns were identified using latent class analysis. The typical meal pattern followed by the majority of the population was characterized by consumption of cereal or toast for breakfast, skipping or consuming a sandwich for light meal, and meat or fish with potatoes, pasta or vegetables for the main meal. Eating patterns differed on weekends, and those participants who consumed meat and eggs for breakfast instead of breakfast cereal and skipped light meal were more likely to have an unhealthier dietary pattern, a higher diastolic blood pressure, and increased serum ferritin. The application of data reduction techniques to simplify the multifaceted nature of dietary data is a useful approach to derive patterns, which might shed further light on the typical dietary patterns followed by populations.
Published:
2018-03
Title:
Internist, anesthesiologist and surgeon use of ketogenic diet. [Review]
Authors:
Cenci, Lorenzo; Paoli, Antonio; Omar, Hesham R.; Dalvi, Prachiti; Camporesi, Enrico M.; Mangar, Devanand; Quartesan, Silvia; Fiorito, Alberto; Bosco, Gerardo
Abstract:
Ketogenic diet is being increasingly utilized in recent decades because of its success as an effective tool for short and intermediate-term weight loss. Promoting physiological ketosis from a drastically low carbohydrate diet is the fundamental basis for this diet regime. Though debated, these diets have been demonstrated to be effective, at least in the short- to medium terms, to manage excess weight, hyperlipidemia, and other cardiovascular risk factors. We reviewed the cardiovascular, metabolic, anesthetic, and postsurgical profiles in the literature and summarized technical issues of anesthesia and surgery along with long-term changes from published papers. Doubts with ketogenic diet were raised due to possible renal damage caused by significant excretion of nitrogen found in animal models, the effects of acidosis, and the concerns of increasing triglycerides and cholesterol levels. Though current literature supports the efficacy of very low carbohydrate keto-diets their potential negative effects on renal function and acidosis are debated. An increase in nitrogen excretion during protein metabolism in the postoperative period could lead to renal damage. Research on the value of ketogenic diets is emerging because of its value in weight loss and in managing other pathologies.
Published:
2018-03
Title:
MERRF Classification: Implications for Diagnosis and Clinical Trials
Authors:
Finsterer, Josef; Zarrouk-Mahjoub, Sinda; Shoffner, John M.
Abstract:
BACKGROUND Given the etiologic heterogeneity of disease classification using clinical phenomenology, we employed contemporary criteria to classify variants associated with myoclonic epilepsy with ragged-red fibers (MERRF) syndrome and to assess the strength of evidence of gene-disease associations. Standardized approaches are used to clarify the definition of MERRF, which is essential for patient diagnosis, patient classification, and clinical trial design. METHODS Systematic literature and database search with application of standardized assessment of gene-disease relationships using modified Smith criteria and of variants reported to be associated with MERRF using modified Yarham criteria. RESULTS Review of available evidence supports a gene-disease association for two MT-tRNAs and for POLG. Using modified Smith criteria, definitive evidence of a MERRF gene-disease association is identified for MT-TK. Strong gene-disease evidence is present for MT-TL1 and POLG. Functional assays that directly associate variants with oxidative phosphorylation impairment were critical to mtDNA variant classification. In silico analysis was of limited utility to the assessment of individual MT-tRNA variants. With the use of contemporary classification criteria, several mtDNA variants previously reported as pathogenic or possibly pathogenic are reclassified as neutral variants. CONCLUSIONS MERRF is primarily an MT-TK disease, with pathogenic variants in this gene accounting for ∼90% of MERRF patients. Although MERRF is phenotypically and genotypically heterogeneous, myoclonic epilepsy is the clinical feature that distinguishes MERRF from other categories of mitochondrial disorders. Given its low frequency in mitochondrial disorders, myoclonic epilepsy is not explained simply by an impairment of cellular energetics. Although MERRF phenocopies can occur in other genes, additional data are needed to establish a MERRF disease-gene association. This approach to MERRF emphasizes standardized classification rather than clinical phenomenology, thus improving patient diagnosis and clinical trial design.
Published:
2018-03
Title:
Modifiable "Predictors" of Zinc Status in Toddlers
Authors:
Daniels, Lisa; Williams, Sheila M.; Gibson, Rosalind S.; Taylor, Rachael W.; Samman, Samir; Heath, Anne-Louise M.
Abstract:
Suboptimal zinc status is common in very young children and likely associated with increased risk of infection and detrimental effects on growth. No studies have determined potentially modifiable "predictors" of zinc status in toddlers from high-income countries. This cross-sectional analysis of 115 toddlers from the Baby-Led Introduction to SolidS (BLISS) study used weighed diet records (three non-consecutive days) to assess dietary intake, and a venous blood sample (trace-element free techniques) to assess plasma zinc, at 12 months of age. "Predictors" of plasma zinc were determined by univariate analysis and multiple regression. Mean (SD) plasma zinc was 9.7 (1.5) µmol/L, 60% were below the IZiNCG reference limit of
Published:
2018-03
Title:
Plant-based diets: Reducing cardiovascular risk by improving sleep quality?
Authors:
St-Onge, Marie-Pierre; Crawford, Allison; Aggarwal, Brooke
Abstract:
Purpose of review: The goal of this review is to evaluate recent research related to the effects of plant-based diets on sleep patterns. We discuss plausible mechanisms for the link between plant-based diets and sleep, and provide suggestions for future research in this area. Recent findings: Short sleep duration and poor sleep quality have been shown to negatively affect individual dietary habits, through enhanced appetite, increased overall caloric intake, as well as lower diet quality. Emerging data also indicate a novel bi-directional association by which dietary choices may also influence sleep duration and quality, but little is known about dietary patterns and their influence on sleep. Epidemiological studies report associations between Mediterranean diet eating patterns and sleep quality, suggesting a benefit of plant-rich diet consumption on sleep. The high isoflavone and tryptophan content of these diets may be a mechanism by which plant foods may enhance sleep quality. Summary: Plant-based diets may provide additional benefits to health via their potential effects on sleep quality. Research is needed to establish a causal relation between a plant-rich dietary pattern and sleep health.
Published:
2018-03
Title:
Triglycerides cross the blood–brain barrier and induce central leptin and insulin receptor resistance
Authors:
Banks, W. A.; Farr, S. A.; Salameh, T. S.; Niehoff, M. L.; Rhea, E. M.; Morley, J. E.; Hanson, A. J.; Hansen, K. M.; Craft, S.
Abstract:
Resistance at the brain receptors for leptin and insulin has been associated with increased feeding, obesity and cognitive impairments. The causal agent for central resistance is unknown but could be derived from the blood. Here we postulate whether hypertriglyceridemia, the major dyslipidemia of the metabolic syndrome, could underlie central leptin and insulin resistance.
Published:
2018-03
Title:
A cellular and molecular view of T helper 17 cell plasticity in autoimmunity
Authors:
Stadhouders, Ralph; Lubberts, Erik; Hendriks, Rudi W.
Abstract:
Since the original identification of the T helper 17 (Th17) subset in 2005, it has become evident that these cells do not only contribute to host defence against pathogens, such as bacteria and fungi, but that they are also critically involved in the pathogenesis of many autoimmune diseases. In contrast to the classic Th1 and Th2 cells, which represent rather stably polarized subsets, Th17 cells display remarkable heterogeneity and plasticity. This has been attributed to the characteristics of the key transcription factor that guides Th17 differentiation, retinoic acid receptor-related orphan nuclear receptor gamma (RORγ). Unlike the ‘master regulators’ T-bet and GATA3 that orchestrate Th1 and Th2 differentiation, respectively, RORγ controls transcription at relatively few loci in Th17 cells. Moreover, its expression is not stabilized by positive feedback loops but rather influenced by environmental cues, allowing for substantial functional plasticity. Importantly, a subset of IL-17/IFNγ double-producing Th17 cells was identified in both human and mouse models. Evidence is accumulating that these IL-17/IFNγ double-producing cells are pathogenic drivers in autoimmune diseases, including rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. In addition, IL-17/IFNγ double-producing cells have been identified in disorders in which the role of autoimmunity remains unclear, such as sarcoidosis. The observed plasticity of Th17 cells towards the Th1 phenotype can be explained by extensive epigenetic priming of the IFNG locus in Th17 cells. In fact, Th17 cells display an IFNG chromatin landscape that is remarkably similar to that of Th1 cells. On the other hand, pathogenic capabilities of Th17 cells can be restrained by stimulating IL-10 production and transdifferentiation into IL-10 producing T regulatory type 1 (Tr1) cells. In this review, we discuss recent advances in our knowledge on the cellular and molecular mechanisms involved in Th17 differentiation, heterogeneity and plasticity. We focus on transcriptional regulation of the Th17 expression program, the epigenetic dynamics involved, and how genetic variants associated with autoimmunity may affect immune responses through distal gene regulatory elements. Finally, the implications of Th17 cell plasticity for the pathogenesis and treatment of human autoimmune diseases will be discussed.
Published:
2018-02
Title:
Adipositas und chronische Inflammation bei phlebologischen und lymphologischen Erkrankungen
Authors:
Faerber, G.
Abstract:
Zusammenfassung Die Prävalenz der Adipositas ist in den letzten 15 Jahren weiter stark angestiegen. Dabei fällt besonders die deutliche Zunahme der morbiden Adipositas auf, die wiederum bei den Älteren besonders ausgeprägt ist. Da mit dem Alter auch venöse Thromboembolien, chronisch venöse Insuffizienz und sekundäre Lymphödeme zunehmen, steigt die Zahl der Patienten mit venösen oder lymphatischen Erkrankungen, die gleichzeitig schwer adipös und häufig multimorbide sind, überproportional an. Die Adipositas, vor allem die viszerale, verschlechtert alle Ödemerkrankungen, erhöht das Risiko für thromboembolische Erkrankungen und postthrombotisches Syndrom und kann alleinige Ursache sein für die Adipositas-assoziierte funktionelle Veneninsuffizienz ohne Nachweis von Obstruktion oder Reflux. Das Adipositasassoziierte Lymphödem stellt inzwischen den größten Anteil unter den sekundären Lymphödemen. Mehr als 50 Prozent der Lipödempatientinnen sind adipös, die bei ihnen im Verlauf zu beobachtenden sekundären Lymphödeme in der Regel Folge der Adipositas, nicht des Lipödems. Die Symptomatik wird bei allen Krankheitsbildern durch Gewichtsreduktion gebessert. Neben mechanischen Faktoren wie der Erhöhung des intraabdominalen und intertriginösen Drucks, der wiederum zu einer venösen Drucksteigerung in den Beingefäßen führt, sind es vor allem die durch die Zunahme des viszeralen Fettgewebes verursachten metabolischen, chronisch inflammatorischen und prothrombotischen Prozesse, die für diese Zusammenhänge verantwortlich sind, erkennbar an niedrigen Spiegeln von Adiponektin und hohen von Leptin, Insulin, intaktem Proinsulin, PAI-1 sowie proinflammatorischen Zytokinen (Il-6, Il-8, TNF-α). Therapeutische Maßnahmen müssen also in erster Linie auf die Reduktion der viszeralen Adipositas und damit der Hyperinsulinämie bzw. der Insulinresistenz sowie auf die Bekämpfung der chronischen Entzündung abzielen. , Summary The prevalence of obesity has continued to rise considerably during the last 15 years. There is a striking increase of cases with morbid obesity (BMI over 40 Kg/m2), especially among the elderly. Since venous thromboembolic events, chronic venous insufficiency and secondary lymphoedema also increase with age, the number of patients who suffer from these conditions and, at the same time, are obese and often multimorbid, rises disproportionately. Obesity, especially if it is visceral, causes all sorts of oedema to deteriorate, increases the risk of thromboembolic events and postthrombotic syndrome and can be the sole cause of the so called obesity-associated dependency- syndrome, or rather the obesity-associated functional venous insufficiency without obstruction or reflux, as it ought to be called, with its skin lesions characteristic of CEAP stages C4 to C6. Among the various causes of secondary lymphoedema obesity is by now the most common. Of patients suffering from lipoedema more than 50 percent are obese, with the secondary lymphoedema often to be seen in those cases being the direct consequence of obesity, not the lipoedema itself. In all the conditions mentioned above symptoms can be ameliorated by weight loss. Aside from mechanical factors like intraabdominal and intertriginous pressure which in turn raise the intravenous pressure in the legs, it is foremost the metabolic, proinflammatory and procoagulatory effects of the augmented visceral fat tissue which can explain the correlation between obesity and thrombosis, oedema and, probably, the skin changes, too. These effects can be identified by low levels of adiponectin, which has antiinflammatory and vasoprotective qualities, and high levels of leptin, characteristic of leptin resistance, inflammation and insulin resistance, insulin and intact proinsulin (precursor of insulin, indicating β-cell insufficiency). Plasminogen Activator Inhibitor-1 (PAI-1), preventing fibrinolysis, and proinflammatory cytokines like Interleukin-6 (Il-6), Interleukin-8 (Il-8) and Tumour Necrosis Factor-α (TNF-α) are also found to be raised. In addition to treating the acute or chronic symptoms by anticoagulation, compression, manual lymphdrainage and wound care, therapeutic measures must endeavour to sustainably reduce visceral fat tissue, and thus hyperinsulinaemia, insulin resistance and inflammation. English version available at: www.phlebologieonline.de
Published:
2018-02
Title:
Dietary patterns, dietary biomarkers, and kidney disease in patients with type 2 diabetes: a repeated-measure study in Taiwan
Authors:
Hsin-Fang Chung; Chih-Cheng Hsu; Mamun, Abdullah Al; Long, Kurt Z.; Ya-Fang Huang; Shyi-Jang Shin; Shang-Jyh Hwang; Meng-Chuan Huang; Chung, Hsin-Fang; Hsu, Chih-Cheng; Huang, Ya-Fang; Shin, Shyi-Jang; Hwang, Shang-Jyh; Huang, Meng-Chuan
Abstract:
Background and Objectives: Western dietary patterns have been linked with kidney disease. This study investigated the association between Chinese dietary patterns and kidney disease in a Taiwanese population with type 2 diabetes and evaluated dietary fatty acid patterns, a kidney-related dietary biomarker.Methods and Study Design: We recruited 838 patients with type 2 diabetes and used their dietary and renal data obtained from three repeated measures in 2008, 2009 and 2010. Diet was assessed using food-frequency questionnaires, and factor analysis was performed to identify dietary patterns. Albuminuria was defined by having an albumin-to-creatinine ratio >=30 mg/g and kidney dysfunction by estimated glomerular filtration rate
Published:
2018-02
Title:
Effectiveness and Safety of a Probiotic-Mixture for the Treatment of Infantile Colic: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial with Fecal Real-Time PCR and NMR-Based Metabolomics Analysis
Authors:
Baldassarre, Maria Elisabetta; Di Mauro, Antonio; Tafuri, Silvio; Rizzo, Valentina; Gallone, Maria Serena; Mastromarino, Paola; Capobianco, Daniela; Laghi, Luca; Zhu, Chenglin; Capozza, Manuela; Laforgia, Nicola
Abstract:
Introduction: To investigate the effectiveness and the safety of a probiotic-mixture (Vivomixx®, Visbiome®, DeSimone Formulation®; Danisco-DuPont, Madison, WI, USA) for the treatment of infantile colic in breastfed infants, compared with a placebo. Methods: A randomized, double-blind, placebo-controlled trial was conducted in exclusively breastfed infants with colic, randomly assigned to receive a probiotic-mixture or a placebo for 21 days. A structured diary of gastrointestinal events of the infants was given to the parents to complete. Samples of feces were also collected to evaluate microbial content and metabolome using fecal real-time polymerase chain reaction (qPCR) and Nuclear magnetic resonance (NMR)-based analysis. Study registered at ClinicalTrials.gov (NCT01869426). Results: Fifty-three exclusively-breastfed infants completed three weeks of treatment with a probiotic-mixture (n = 27) or a placebo (n = 26). Infants receiving the probiotic-mixture had less minutes of crying per day throughout the study by the end of treatment period (68.4 min/day vs. 98.7 min/day; p = 0.001). A higher rate of infants from the probiotic-mixture group responded to treatment (defined by reduction of crying times of ≥50% from baseline), on day 14, 12 vs. 5 (p = 0.04) and on day 21,26 vs. 17 (p = 0.001). A higher quality of life, assessed by a 10-cm visual analogue scale, was reported by parents of the probiotic-mixture group on day 14, 7.1 ± 1.2 vs. 7.7 ± 0.9 (p = 0.02); and on day 21, 6.7 ± 1.6 vs. 5.9 ± 1.0 (p = 0.001). No differences between groups were found regarding anthropometric data, bowel movements, stool consistency or microbiota composition. Probiotics were found to affect the fecal molecular profile. No adverse events were reported. Conclusions: Administration of a probiotic-mixture appears safe and reduces inconsolable crying in exclusively breastfed infants.
Published:
2018-02
Title:
Gut microbiota functions: metabolism of nutrients and other food components
Authors:
Rowland, Ian; Gibson, Glenn; Heinken, Almut; Scott, Karen; Swann, Jonathan; Thiele, Ines; Tuohy, Kieran
Abstract:
The diverse microbial community that inhabits the human gut has an extensive metabolic repertoire that is distinct from, but complements the activity of mammalian enzymes in the liver and gut mucosa and includes functions essential for host digestion. As such, the gut microbiota is a key factor in shaping the biochemical profile of the diet and, therefore, its impact on host health and disease. The important role that the gut microbiota appears to play in human metabolism and health has stimulated research into the identification of specific microorganisms involved in different processes, and the elucidation of metabolic pathways, particularly those associated with metabolism of dietary components and some host-generated substances. In the first part of the review, we discuss the main gut microorganisms, particularly bacteria, and microbial pathways associated with the metabolism of dietary carbohydrates (to short chain fatty acids and gases), proteins, plant polyphenols, bile acids, and vitamins. The second part of the review focuses on the methodologies, existing and novel, that can be employed to explore gut microbial pathways of metabolism. These include mathematical models, omics techniques, isolated microbes, and enzyme assays.
Published:
2018-02
Title:
Incretin hormones: Their role in health and disease
Authors:
Nauck, Michael A.; Meier, Juris J.
Abstract:
Incretin hormones are gut peptides that are secreted after nutrient intake and stimulate insulin secretion together with hyperglycaemia. GIP (glucose-dependent insulinotropic polypeptide) und GLP-1 (glucagon-like peptide-1) are the known incretin hormones from the upper (GIP, K cells) and lower (GLP-1, L cells) gut. Together, they are responsible for the incretin effect: a two- to three-fold higher insulin secretory response to oral as compared to intravenous glucose administration. In subjects with type 2 diabetes, this incretin effect is diminished or no longer present. This is the consequence of a substantially reduced effectiveness of GIP on the diabetic endocrine pancreas, and of the negligible physiological role of GLP-1 in mediating the incretin effect even in healthy subjects. However, the insulinotropic and glucagonostatic effects of GLP-1 are preserved in subjects with type 2 diabetes to the degree that pharmacological stimulation of GLP-1 receptors significantly reduces plasma glucose and improves glycaemic control. Thus, it has become a parent compound of incretin-based glucose-lowering medications (GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase-4 or DPP-4). GLP-1, in addition, has multiple effects on various organ systems. Most relevant are a reduction in appetite and food intake, leading to weight loss in the long term. Since GLP-1 secretion from the gut seems to be impaired in obese subjects, this may even indicate a role in the pathophysiology of obesity. Along these lines, an increased secretion of GLP-1 induced by delivering nutrients to lower parts of the small intestines (rich in L cells) may be one factor (among others like peptide YY) explaining weight loss and improvements in glycaemic control after bariatric surgery (e.g., Roux-en-Y gastric bypass). GIP and GLP-1, originally characterized as incretin hormones, have additional effects in adipose cells, bone, and the cardiovascular system. Especially, the latter have received attention based on recent findings that GLP-1 receptor agonists such as liraglutide reduce cardiovascular events and prolong life in high-risk patients with type 2 diabetes. Thus, incretin hormones have an important role physiologically, namely they are involved in the pathophysiology of obesity and type 2 diabetes, and they have therapeutic potential that can be traced to well-characterized physiological effects.
Published:
2018-02
Title:
Influence of the neural microenvironment on prostate cancer
Authors:
Coarfa, Christian; Florentin, Diego; Putluri, NagiReddy; Ding, Yi; Au, Jason; He, Dandan; Ragheb, Ahmed; Frolov, Anna; Michailidis, George; Lee, MinJae; Kadmon, Dov; Miles, Brian; Smith, Christopher; Ittmann, Michael; Rowley, David; Sreekumar, Arun; Creighton, Chad J.; Ayala, Gustavo
Abstract:
BACKGROUND: Nerves are key factors in prostate cancer (PCa), but the functional role of innervation in prostate cancer is poorly understood. PCa induced neurogenesis and perineural invasion (PNI), are associated with aggressive disease. METHOD: We denervated rodent prostates chemically and physically, before orthotopically implanting cancer cells. We also performed a human neoadjuvant clinical trial using botulinum toxin type A (Botox) and saline in the same patient, before prostatectomy. RESULT: Bilateral denervation resulted in reduced tumor incidence and size in mice. Botox treatment in humans resulted in increased apoptosis of cancer cells in the Botox treated side. A similar denervation gene array profile was identified in tumors arising in denervated rodent prostates, in spinal cord injury patients and in the Botox treated side of patients. Denervation induced exhibited a signature gene profile, indicating translation and bioenergetic shutdown. Nerves also regulate basic cellular functions of non-neoplastic epithelial cells. CONCLUSION: Nerves play a role in the homeostasis of normal epithelial tissues and are involved in prostate cancer tumor survival. This study confirms that interactions between human cancer and nerves are essential to disease progression. This work may make a major impact in general cancer treatment strategies, as nerve/cancer interactions are likely important in other cancers as well. Targeting the neural microenvironment may represent a therapeutic approach for the treatment of human prostate cancer.
Published:
2018-02
Title:
Intermittent energy restriction improves weight loss efficiency in obese men: the MATADOR study
Authors:
Byrne, N. M.; Sainsbury, A.; King, N. A.; Hills, A. P.; Wood, R. E.
Abstract:
Background/Objectives:The MATADOR (Minimising Adaptive Thermogenesis And Deactivating Obesity Rebound) study examined whether intermittent energy restriction (ER) improved weight loss efficiency compared with continuous ER and, if so, whether intermittent ER attenuated compensatory responses associated with ER.Subjects/Methods:Fifty-one men with obesity were randomised to 16 weeks of either: (1) continuous (CON), or (2) intermittent (INT) ER completed as 8 × 2-week blocks of ER alternating with 7 × 2-week blocks of energy balance (30 weeks total). Forty-seven participants completed a 4-week baseline phase and commenced the intervention (CON: N=23, 39.4±6.8 years, 111.1±9.1 kg, 34.3±3.0 kg m−2; INT: N=24, 39.8±9.5 years, 110.2±13.8 kg, 34.1±4.0 kg m−2). During ER, energy intake was equivalent to 67% of weight maintenance requirements in both groups. Body weight, fat mass (FM), fat-free mass (FFM) and resting energy expenditure (REE) were measured throughout the study.Results:For the N=19 CON and N=17 INT who completed the intervention per protocol, weight loss was greater for INT (14.1±5.6 vs 9.1±2.9 kg; P<0.001). INT had greater FM loss (12.3±4.8 vs 8.0±4.2 kg; P<0.01), but FFM loss was similar (INT: 1.8±1.6 vs CON: 1.2±2.5 kg; P=0.4). Mean weight change during the 7 × 2-week INT energy balance blocks was minimal (0.0±0.3 kg). While reduction in absolute REE did not differ between groups (INT: -502±481 vs CON: −624±557 kJ d−1; P=0.5), after adjusting for changes in body composition, it was significantly lower in INT (INT: −360±502 vs CON: −749±498 kJ d−1; P
Published:
2018-02
Title:
Intermittent metabolic switching, neuroplasticity and brain health
Authors:
Mattson, Mark P.; Moehl, Keelin; Ghena, Nathaniel; Schmaedick, Maggie; Cheng, Aiwu
Abstract:
During evolution, individuals whose brains and bodies functioned well in a fasted state were successful in acquiring food, enabling their survival and reproduction. With fasting and extended exercise, liver glycogen stores are depleted and ketones are produced from adipose-cell-derived fatty acids. This metabolic switch in cellular fuel source is accompanied by cellular and molecular adaptations of neural networks in the brain that enhance their functionality and bolster their resistance to stress, injury and disease. Here, we consider how intermittent metabolic switching, repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting and sleeping), may optimize brain function and resilience throughout the lifespan, with a focus on the neuronal circuits involved in cognition and mood. Such metabolic switching impacts multiple signalling pathways that promote neuroplasticity and resistance of the brain to injury and disease.
Published:
2018-02
Title:
Involvement of Porphyromonas gingivalis in the progression of non-alcoholic fatty liver disease
Authors:
Nakahara, Takashi; Hyogo, Hideyuki; Ono, Atsushi; Nagaoki, Yuko; Kawaoka, Tomokazu; Miki, Daiki; Tsuge, Masataka; Hiraga, Nobuhiko; Hayes, Clair Nelson; Hiramatsu, Akira; Imamura, Michio; Kawakami, Yoshiiku; Aikata, Hiroshi; Ochi, Hidenori; Abe-Chayama, Hiromi; Furusho, Hisako; Shintani, Tomoaki; Kurihara, Hidemi; Miyauchi, Mutsumi; Takata, Takashi
Abstract:
Background and Aims: The risk factors in the progression of nonalcoholic fatty liver disease (NAFLD) have not been fully clarified. Porphyromonas gingivalis (P.g) has been considered to be a confounding risk factor for systemic diseases. We aimed to evaluate the effect of P.g infection on risk of progression to NASH.Methods: (1) Serum IgG antibody titers against P.g fimbriae (fimA) in 200 biopsy-proven NAFLD patients were measured by ELISA and compared with histological findings. (2) C57BL/6J mice were fed a control diet (CD) or high-fat diet (HFD) with or without P.g-odontogenic infection and analyzed histologically. Mouse livers were analyzed using CE-TOFMS and LC-TOFMS.Results: (1) A significant correlation between fibrosis progression and antibody titers against P.g possessing fimA type 4 was identified (P = 0.0081). Multivariate analysis identified older age and type 4 P.g-positivity as risk factors for advanced fibrosis. (2) Fibrosis and steatosis were more severe in HFD P.g(+) mice compared with HFD P.g(-) mice. In metabolome analysis, fatty acid metabolism was significantly disrupted with HFD in P.g-infected mouse livers. Monounsaturated/saturated fatty acid ratios were significantly higher in the HFD P.g(+) group than in the HFD P.g(-) group (P
Published:
2018-02
Title:
Maternal diet during pregnancy and micronuclei frequency in peripheral blood T lymphocytes in mothers and newborns (Rhea cohort, Crete)
Authors:
O’Callaghan-Gordo, Cristina; Kogevinas, Manolis; Pedersen, Marie; Fthenou, Eleni; Espinosa, Ana; Tsiapa, Xristina; Chalkiadaki, Georgia; Daraki, Vasiliki; Dermitzaki, Eirini; Decordier, Ilse; Farmer, Peter B.; Georgiadis, Panagiotis; Georgiou, Vaggelis; Kyrtopoulos, Soterios A.; Merlo, Domenico Franco; Romaguera, Dora; Roumeliotaki, Theano; Sarri, Katerina; Törnqvist, Margareta; Loock, Kim Vande
Abstract:
Purpose: The study assessed whether diet and adherence to cancer prevention guidelines during pregnancy were associated with micronucleus (MN) frequency in mothers and newborns. MN is biomarkers of early genetic effects that have been associated with cancer risk in adults.Methods: A total of 188 mothers and 200 newborns from the Rhea cohort (Greece) were included in the study. At early-mid pregnancy, we conducted personal interviews and a validated food frequency questionnaire was completed. With this information, we constructed a score reflecting adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention guidelines on diet, physical activity and body fatness. At delivery, maternal and/or cord blood was collected to measure DNA and hemoglobin adducts of dietary origin and frequencies of MN in binucleated and mononucleated T lymphocytes (MNBN and MNMONO).Results: In mothers, higher levels of red meat consumption were associated with increased MNBN frequency [2nd tertile IRR = 1.34 (1.00, 1.80), 3rd tertile IRR = 1.33 (0.96, 1.85)] and MNMONO frequency [2nd tertile IRR = 1.53 (0.84, 2.77), 3rd tertile IRR = 2.69 (1.44, 5.05)]. The opposite trend was observed for MNBN in newborns [2nd tertile IRR = 0.64 (0.44, 0.94), 3rd tertile IRR = 0.68 (0.46, 1.01)], and no association was observed with MNMONO. Increased MN frequency in pregnant women with high red meat consumption is consistent with previous knowledge.Conclusions: Our results also suggest exposure to genotoxics during pregnancy might affect differently mothers and newborns. The predictive value of MN as biomarker for childhood cancer, rather than adulthood, remains unclear. With few exceptions, the association between maternal carcinogenic exposures during pregnancy and childhood cancer or early biologic effect biomarkers remains poorly understood.
Published:
2018-02
Title:
Measuring Burnout Among Psychiatry Clerkship Directors
Authors:
Rakofsky, Jeffrey J.; Dallaghan, Gary Beck; Balon, Richard
Abstract:
Objective The primary purpose of this study was to determine the prevalence of burnout among Psychiatry clerkship directors. Methods Psychiatry clerkship directors were solicited via email to complete an electronic version of the Maslach Burnout Inventory-General Survey and the Respondent Information Form. Results Fifty-four out of 110 surveys (49%) were completed. Fourteen percent of respondents scored in the “high exhaustion” category, 21.6% scored in the “low professional efficacy” category, 20.4% scored in the “high cynicism” category, and 15.1% of respondents met threshold for at least two of the three categories. Those who scored in the “low professional efficacy” category reported higher levels of salary support for research, while those who scored in the “high cynicism” category reported lower levels of salary support at a trend level. Those who scored in the “high cynicism” category were younger. Conclusions Approximately 14–22 percent of psychiatry clerkship directors reported some level of burnout depending on the subscale used. Future studies should aim to better identify those clerkship directors who are at greatest risk for becoming burned out by their educational role and to clarify the link between salary support for research, age, and burnout.
Published:
2018-02
Title:
Metabolic adaptations to HFHS overfeeding: how whole body and tissues postprandial metabolic flexibility adapt in Yucatan mini-pigs
Authors:
Polakof, Sergio; Rémond, Didier; Bernalier-Donadille, Annick; Rambeau, Mathieu; Pujos-Guillot, Estelle; Comte, Blandine; Dardevet, Dominique; Savary-Auzeloux, Isabelle
Abstract:
Purpose: In the present study, we aimed to metabolically characterize the postprandial adaptations of the major tissues involved in energy, lipids and amino acids metabolisms in mini-pigs.Method: Mini-pigs were fed on high-fat–high-sucrose (HFHS) diet for 2 months and several tissues explored for metabolic analyses. Further, the urine metabolome was followed over the time to picture the metabolic adaptations occurring at the whole body level following overfeeding.Results: After 2 months of HFHS consumption, mini-pigs displayed an obese phenotype characterized by high circulating insulin, triglycerides and cholesterol levels. At the tissue level, a general (muscle, adipose tissue, intestine) reduction in the capacity to phosphorylate glucose was observed. This was also supported by the enhanced hepatic gluconeogenesis potential, despite the concomitant normoglycaemia, suggesting that the high circulating insulin levels would be enough to maintain glucose homoeostasis. The HFHS feeding also resulted in a reduced capacity of two other pathways: the de novo lipogenesis, and the branched-chain amino acids transamination. Finally, the follow-up of the urine metabolome over the time allowed determining breaking points in the metabolic trajectory of the animals.Conclusions: Several features confirmed the pertinence of the animal model, including increased body weight, adiposity and porcine obesity index. At the metabolic level, we observed a perturbed glucose and amino acid metabolism, known to be related to the onset of the obesity. The urine metabolome analyses revealed several metabolic pathways potentially involved in the obesity onset, including TCA (citrate, pantothenic acid), amino acids catabolism (cysteine, threonine, leucine).
Published:
2018-02
Title:
Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance
Authors:
Pickles, Sarah; Vigié, Pierre; Youle, Richard J.
Abstract:
The maintenance of a healthy and functional mitochondrial network is critical during development as well as throughout life in the response to physiological adaptations and stress conditions. Owing to their role in energy production, mitochondria are exposed to high levels of reactive oxygen species, making them particularly vulnerable to mitochondrial DNA mutations and protein misfolding. Given that mitochondria are formed from proteins encoded by both nuclear and mitochondrial genomes, an additional layer of complexity is inherent in the coordination of protein synthesis and the mitochondrial import of nuclear-encoded proteins. For these reasons, mitochondria have evolved multiple systems of quality control to ensure that the requisite number of functional mitochondria are present to meet the demands of the cell. These pathways work to eliminate damaged mitochondrial proteins or parts of the mitochondrial network by mitophagy and renew components by adding protein and lipids through biogenesis, collectively resulting in mitochondrial turnover. Mitochondrial quality control mechanisms are multi-tiered, operating at the protein, organelle and cell levels. Herein, we discuss mitophagy in different physiological contexts and then relate it to other quality control pathways, including the unfolded protein response, shedding of vesicles, proteolysis, and degradation by the ubiquitin–proteasome system. Understanding how these pathways contribute to the maintenance of mitochondrial homeostasis could provide insights into the development of targeted treatments when these systems fail in disease. Pickles, Vigié and Youle discuss mitochondrial turnover by mitophagy and highlight other mitochondrial quality control pathways, including the unfolded protein response, vesicle shedding, proteolysis, and degradation by the ubiquitin–proteasome system.
Published:
2018-02
Title:
Preparing Physical and Occupational Therapists to Be Health Promotion Practitioners: A Call for Action
Authors:
Morris, David M.; Jenkins, Gavin R.
Abstract:
Experts around the world support the integration of health promotion and wellness (HPW) services into traditional health care services. If successfully executed, the addition of HPW services would reduce rates of death and disability and significantly reduce health care costs. While all health care providers should be engaged in providing HPW services, many believe that physical therapists (PTs) and occupational therapists (OTs) are uniquely positioned to provide these services. However, research suggests that clinicians in both fields may fall short in doing so. Likewise, research indicates that entry-level educational programs inadequately prepare PT and OT students to be HPW practitioners. The overall purpose of this paper is to provide recommendations to educators for preparing PT and OT students and clinicians to better meet the HPW needs of the clients and patients they serve.
Published:
2018-02
Title:
Recent advances in detecting mitochondrial DNA heteroplasmic variations
Authors:
Duan, Mengqin; Tu, Jing; Lu, Zuhong
Abstract:
The co-existence of wild-type and mutated mitochondrial DNA (mtDNA) molecules termed heteroplasmy becomes a research hot point of mitochondria. In this review, we listed several methods of mtDNA heteroplasmy research, including the enrichment of mtDNA and the way of calling heteroplasmic variations. At the present, while calling the novel ultra-low level heteroplasmy, high-throughput sequencing method is dominant while the detection limit of recorded mutations is accurate to 0.01% using the other quantitative approaches. In the future, the studies of mtDNA heteroplasmy may pay more attention to the single-cell level and focus on the linkage of mutations.
Published:
2018-02
Title:
Systematic review of the effects of the intestinal microbiota on selected nutrients and non-nutrients
Authors:
Shortt, Colette; Hasselwander, Oliver; Meynier, Alexandra; Nauta, Arjen; Fernández, Estefanía Noriega; Putz, Peter; Rowland, Ian; Swann, Jonathan; Türk, Jessica; Vermeiren, Joan; Antoine, Jean-Michel
Abstract:
PURPOSE: There is considerable interest in the effects of the intestinal microbiota (IM) composition, its activities in relation with the metabolism of dietary substrates and the impact these effects may have in the development and prevention of certain non-communicable diseases. It is acknowledged that a complex interdependence exists between the IM and the mammalian host and that the IM possesses a far greater diversity of genes and repertoire of metabolic and enzymatic capabilities than their hosts. However, full knowledge of the metabolic activities and interactions of the IM and the functional redundancy that may exist are lacking. Thus, the current review aims to assess recent literature relating to the role played by the IM in the absorption and metabolism of key nutrients and non-nutrients. METHODS: A systematic review (PROSPERO registration: CRD42015019087) was carried out focussing on energy and the following candidate dietary substrates: protein, carbohydrate, fat, fibre, resistant starch (RS), and polyphenols to further understand the effect of the IM on the dietary substrates and the resulting by-products and host impacts. Particular attention was paid to the characterisation of the IM which are predominantly implicated in each case, changes in metabolites, and indirect markers and any potential impacts on the host. RESULTS: Studies show that the IM plays a key role in the metabolism of the substrates studied. However, with the exception of studies focusing on fibre and polyphenols, there have been relatively few recent human studies specifically evaluating microbial metabolism. In addition, comparison of the effects of the IM across studies was difficult due to lack of specific analysis/description of the bacteria involved. Considerable animal-derived data exist, but experience suggests that care must be taken when extrapolating these results to humans. Nevertheless, it appears that the IM plays a role in energy homeostasis and that protein microbial breakdown and fermentation produced ammonia, amines, phenols and branch chain fatty acids, and a greater diversity in the microbes present. Few recent studies appear to have evaluated the effect of the IM composition and metabolism per se in relation with digestible dietary carbohydrate or fat in humans. Intakes of RS and prebiotics altered levels of specific taxa that selectively metabolised specific prebiotic/carbohydrate-type substances and levels of bifidobacteria and lactobacilli were observed to increase. In controlled human studies, consistent data exist that show a correlation between the intake of fibre and an increase in bifidobacteria and short-chain fatty acids, in particular butyrate, which leads to lower intestinal pH. Dietary polyphenols rely on modification either by host digestive enzymes or those derived from the IM for absorption to occur. In the polyphenol-related studies, a large amount of inter-individual variation was observed in the microbial metabolism and absorption of certain polyphenols. CONCLUSIONS: The systematic review demonstrates that the IM plays a major role in the breakdown and transformation of the dietary substrates examined. However, recent human data are limited with the exception of data from studies examining fibres and polyphenols. Results observed in relation with dietary substrates were not always consistent or coherent across studies and methodological limitations and differences in IM analyses made comparisons difficult. Moreover, non-digestible components likely to reach the colon are often not well defined or characterised in studies making comparisons between studies difficult if not impossible. Going forward, further rigorously controlled randomised human trials with well-defined dietary substrates and utilizing omic-based technologies to characterise and measure the IM and their functional activities will advance the field. Current evidence suggests that more detailed knowledge of the metabolic activities and interactions of the IM hold considerable promise in relation with host health.
Published:
2018-02
Title:
The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids
Authors:
Jang, Cholsoon; Hui, Sheng; Lu, Wenyun; Cowan, Alexis J.; Morscher, Raphael J.; Lee, Gina; Liu, Wei; Tesz, Gregory J.; Birnbaum, Morris J.; Rabinowitz, Joshua D.
Abstract:
Excessive consumption of sweets is a risk factor for metabolic syndrome. A major chemical feature of sweets is fructose. Despite strong ties between fructose and disease, the metabolic fate of fructose in mammals remains incompletely understood. Here we use isotope tracing and mass spectrometry to track the fate of glucose and fructose carbons in vivo, finding that dietary fructose is cleared by the small intestine. Clearance requires the fructose-phosphorylating enzyme ketohexokinase. Low doses of fructose are 90% cleared by the intestine, with only trace fructose but extensive fructose-derived glucose, lactate, and glycerate found in the portal blood. High doses of fructose (R1 g/kg) overwhelm intestinal fructose absorption and clearance, resulting in fructose reaching both the liver and colonic microbiota. Intestinal fructose clearance is augmented both by prior exposure to fructose and by feeding. We propose that the small intestine shields the liver from otherwise toxic fructose exposure.
Published:
2018-02
Title:
Tissue sodium content is elevated in the skin and subcutaneous adipose tissue in women with lipedema
Authors:
Crescenzi, Rachelle; Marton, Adriana; Donahue, Paula M.C.; Mahany, Helen B.; Lants, Sarah K.; Wang, Ping; Beckman, Joshua A.; Donahue, Manus J.; Titze, Jens
Abstract:
Objective To test the hypothesis that tissue sodium and adipose content are elevated in patients with lipedema; if confirmed, this could establish precedence for tissue sodium and adipose content representing a discriminatory biomarker for lipedema. Methods Participants with lipedema (n=10) and control (n=11) volunteers matched for biological sex, age, body-mass-index, and calf circumference were scanned noninvasively with 3.0T sodium and conventional proton MRI. Standardized tissue sodium content was quantified in skin, subcutaneous adipose tissue (SAT), and calf muscle. Dixon MRI was employed to quantify tissue fat and water volumes of the calf. Nonparametric statistical tests were applied to compare regional sodium content and fat-to-water volume ratio between groups (significance: two-sided p≤0.05). Results Skin (p=0.01) and SAT (p=0.04) sodium content were elevated in lipedema (skin: 14.9±2.9 mmol/L; SAT: 11.9±3.1 mmol/L) relative to control (skin: 11.9±2.0 mmol/L; SAT: 9.4±1.6 mmol/L) participants. Relative fat volume in the calf was elevated in lipedema (1.2±0.48 ratio) relative to control (0.63±0.26 ratio, p
Published:
2018-02
Title:
A New Fight Against Colon Cancer: As Cancer Rates Rise Among Younger Adults, Researchers Look for New Screening and Treatment Options
Authors:
Bates, M.
Abstract:
Although the overall incidence of colon cancer has been falling over the past few decades, a pair of recent studies revealed a startling trend. In February 2017, researchers published a report showing that colon cancer rates were rising among younger adults. Some skeptics suggested the spike might simply reflect earlier detection and not necessarily represent a real increase in the disease. But a follow-up study found that Gen-Xers and millenials aren't just getting cancer diagnoses earlier; they are dying from colon cancer at slightly higher rates than in previous decades. Death rates among adults aged 20-54 have increased slightly, to 4.3 deaths per 100,000 people in 2014, up from 3.9 per 100,000 in 2004.
Published:
2018-01
Title:
Caloric Restriction and Rapamycin Differentially Alter Energy Metabolism in Yeast
Authors:
Kyung-Mi Choi; Seok-Jin Hong; van Deursen, Jan M.; Sooah Kim; Kyoung Heon Kim; Cheol-Koo Lee; Choi, Kyung-Mi; Hong, Seok-Jin; Kim, Sooah; Kim, Kyoung Heon; Lee, Cheol-Koo
Abstract:
Rapamycin (RM), a drug that inhibits the mechanistic target of rapamycin (mTOR) pathway and responds to nutrient availability, seemingly mimics the effects of caloric restriction (CR) on healthy life span. However, the extent of the mechanistic overlap between RM and CR remains incompletely understood. Here, we compared the impact of CR and RM on cellular metabolic status. Both regimens maintained intracellular ATP through the chronological aging process and showed enhanced mitochondrial capacity. Comparative transcriptome analysis showed that CR had a stronger impact on global gene expression than RM. We observed a like impact on the metabolome and identified distinct metabolites affected by CR and RM. CR severely reduced the level of energy storage molecules including glycogen and lipid droplets, whereas RM did not. RM boosted the production of enzymes responsible for the breakdown of glycogen and lipid droplets. Collectively, these results provide insights into the distinct energy metabolism mechanisms induced by CR and RM, suggesting that these two anti-aging regimens might extend life span through distinctive pathways.
Published:
2018-01
Title:
Diet, Gut Microbiota, and Vitamins D + A in Multiple Sclerosis
Authors:
Riccio, Paolo; Rossano, Rocco
Abstract:
Central to the understanding of the relationships between diet, gut microbiota, and vitamins D and A in multiple sclerosis is low-grade inflammation, which is involved in all chronic inflammatory diseases and is influenced by each of the above effectors. We show that food components have either proinflammatory or anti-inflammatory effects and influence both the human metabolism (the "metabolome") and the composition of gut microbiota. Hypercaloric, high-animal-fat Western diets favor anabolism and change gut microbiota composition towards dysbiosis. Subsequent intestinal inflammation leads to leakage of the gut barrier, disruption of the blood-brain barrier, and neuroinflammation. Conversely, a vegetarian diet, rich in fiber, is coherent with gut eubiosis and a healthy condition. Vitamin D levels, mainly insufficient in a persistent low-grade inflammatory status, can be restored to optimal values only by administration of high amounts of cholecalciferol. At its optimal values (>30 ng/ml), vitamin D requires vitamin A for the binding to the vitamin D receptor and exert its anti-inflammatory action. Both vitamins must be supplied to the subjects lacking vitamin D. We conclude that nutrients, including the nondigestible dietary fibers, have a leading role in tackling the low-grade inflammation associated with chronic inflammatory diseases. Their action is mediated by gut microbiota and any microbial change induced by diet modifies host-microbe interactions in a consequent way, to improve the disease or worsen it.
Published:
2018-01
Title:
Evaluation of a short Food Frequency Questionnaire to assess cardiovascular disease-related diet and lifestyle factors
Authors:
Svendsen, Karianne; Henriksen, Hege Berg; Carlsen, Monica H.; Retterstøl, Kjetil; Østengen, Beate; Telle-Hansen, Vibeke H.; Jacobs Jr., David R.
Abstract:
Background: The Vascular lifestyle-Intervention and Screening in phArmacies (VISA) study investigates diet and lifestyle factors associated with risk of cardiovascular disease (CVD). As part of the study methodology, a short Food Frequency Questionnaire (FFQ), the VISA-FFQ, was adapted from the Norwegian NORDIET-FFQ. Objective: The aim of this study was to evaluate the VISA-FFQ and its ability to estimate intakes of foods and lifestyle factors in screening for elevated risk of CVD. The evaluation included assessment of relative validity of intake of milk fat and assessment of reproducibility of several foods and lifestyle factors. Design: Relative validity of milk fat estimated from the VISA-FFQ was assessed in 307 participants by comparing estimated dietary intake of the fatty acids pentadecanoic acid (15:0) and heptadecanoic acid (17:0), from milk fat with whole blood biomarkers 15:0 and 17:0. Reproducibility was evaluated in 122 participants by comparing consistency in intakes of different foods and lifestyle factors reported by the VISA-FFQ and administered twice with a 4-week interval. Results: Dietary 15:0 milk fat estimated from the VISA-FFQ correlated positively with whole blood 15:0 (r = 0.32, P
Published:
2018-01
Title:
Genetic evidence that carbohydrate-stimulated insulin secretion leads to obesity
Authors:
Astley, Christina M.; Todd, Jennifer N.; Salem, Rany M.; Vedantam, Sailaja; Ebbeling, Cara B.; Huang, Paul L.; Ludwig, David S.; Hirschhorn, Joel N.; Florez, Jose C.
Abstract:
BACKGROUND A fundamental precept of the carbohydrate-insulin model of obesity is that insulin secretion drives weight gain. However, fasting hyperinsulinemia can also be driven by obesity-induced insulin resistance. We used genetic variation to isolate and estimate the potentially causal effect of insulin secretion on body weight. METHODS Genetic instruments of variation of insulin secretion [assessed as insulin concentration 30 min after oral glucose (insulin-30)] were used to estimate the causal relationship between increased insulin secretion and body mass index (BMI), using bidirectional Mendelian randomization analysis of genome-wide association studies. Data sources included summary results from the largest published metaanalyses of predominantly European ancestry for insulin secretion (n = 26037) and BMI (n = 322154), as well as individual-level data from the UK Biobank (n = 138541). Data from the Cardiology and Metabolic Patient Cohort study at Massachusetts General Hospital (n = 1675) were used to validate genetic associations with insulin secretion and to test the observational association of insulin secretion and BMI. RESULTS Higher genetically determined insulin-30 was strongly associated with higher BMI (β = 0.098, P = 2.2 × 10-21), consistent with a causal role in obesity. Similar positive associations were noted in sensitivity analyses using other genetic variants as instrumental variables. By contrast, higher genetically determined BMI was not associated with insulin-30. CONCLUSIONS Mendelian randomization analyses provide evidence for a causal relationship of glucose-stimulated insulin secretion on body weight, consistent with the carbohydrate-insulin model of obesity.
Published:
2018-01
Title:
Lipid-mediated signals that regulate mitochondrial biology
Authors:
Nielson, Jason R.; Rutter, Jared P.
Abstract:
For decades, lipids were assumed to fulfill roles only in energy storage and membrane structure. Recent studies have discovered critical roles for phospholipids, sphingolipids, and sterols in many cellular pathways, including cell signaling and transcriptional regulation. Frequently, lipids from these various classes work together to achieve defined cellular outcomes. Specific mitochondrial lipids are critical for proper assembly of the electron transport chain complexes and for effective responses to mitochondrial damage, including maintenance of mitochondrial protein homeostasis, regulation of mitophagy, and induction of apoptosis. In this Minireview, we will primarily focus on mitochondrial lipid signaling mediated by lipid–protein interactions.
Published:
2018-01
Title:
Metabolomic analysis of serum from rats following long-term intake of Chinese sausage
Authors:
Minxian Rong; Yuesheng Qiu; Yiyuan Wang; Hong Deng; Pei Wang; Yungang Liu
Abstract:
Introduction: Owing to the contamination of chemical pollutants, especially nitrosamines and their precursors, in Chinese sausage, long-term intake of Chinese sausage may have potential health effects. Objection: This study investigated the effects of long-term intake of Chinese sausage with different contaminations of N-nitrosodimethylamine (NDMA) on rat liver and the potential biomarkers in the serum. Methods: Serum metabolomic analysis was performed by gas chromatography--mass spectrometry at weeks 7, 17, 25, and 33; simultaneously, liver histopathological examination was conducted and its relationship with the serum metabolomics was also investigated. Results: In the study, long-term intake of Chinese sausage with different NDMA contents induced signifi- cant changes in serum metabolites and liver histopathology in rats. Metabonomic analysis showed that seven metabolites -- β-alanine, 3-aminoisobutyric acid, aminooxyacetic acid, D-alanyl-D-alanine, pelargonic acid, palmitic acid (PA), and linoleic acid (LA) -- in three sausage diet groups were significantly decreased at four time points, where three other metabolites were notably increased, which included putrescine, ethanolamine phosphate, and taurine. Among the various treatments, the NDMA (sausage-free) group demonstrated the most remarkable changes. Phenylalanine was decreased followed by an increase, and tyrosine persistently declined, both of which were elevated in the NDMA group. In addition, the histopathological result was consistent with that of the serum metabolomic analysis, and the changes in serum metabolites in each sausage diet group and the NDMA group were consistently associated with disorders of lipids, amino acid, and energy metabolism. Conclusion: This work indicates that excessive NDMA content in sausage may cause liver damage.
Published:
2018-01
Title:
Mitochondrial DNA Heteroplasmy and Purifying Selection in the Mammalian Female Germ Line
Authors:
Burr, Stephen P.; Pezet, Mikael; Chinnery, Patrick F.
Abstract:
Inherited mutations in the mitochondrial (mt)DNA are a major cause of human disease, with approximately 1 in 5000 people affected by one of the hundreds of identified pathogenic mtDNA point mutations or deletions. Due to the severe, and often untreatable, symptoms of many mitochondrial diseases, identifying how these mutations are inherited from one generation to the next has been an area of intense research in recent years. Despite large advances in our understanding of this complex process, many questions remain unanswered, with one of the most hotly debated being whether or not purifying selection acts against pathogenic mutations during germline development.
Published:
2018-01
Title:
Movement disorders in genetically confirmed mitochondrial disease and the putative role of the cerebellum
Authors:
Schreglmann, Sebastian R.; Riederer, Franz; Galovic, Marian; Ganos, Christos; Kägi, Georg; Waldvogel, Daniel; Jaunmuktane, Zane; Schaller, Andre; Hidding, Ute; Krasemann, Ernst; Michels, Lars; Baumann, Christian R.; Bhatia, Kailash; Jung, Hans H.
Abstract:
Background: Mitochondrial disease can present as a movement disorder. Data on this entity's epidemiology, genetics, and underlying pathophysiology, however, is scarce. Objective: The objective of this study was to describe the clinical, genetic, and volumetric imaging data from patients with mitochondrial disease who presented with movement disorders. Methods: In this retrospective analysis of all genetically confirmed mitochondrial disease cases from three centers (n = 50), the prevalence and clinical presentation of video-documented movement disorders was assessed. Voxel-based morphometry from high-resolution MRI was employed to compare cerebral and cerebellar gray matter volume between mitochondrial disease patients with and without movement disorders and healthy controls. Results: Of the 50 (30%) patients with genetically confirmed mitochondrial disease, 15 presented with hypokinesia (parkinsonism 3/15), hyperkinesia (dystonia 5/15, myoclonus 3/15, chorea 2/15), and ataxia (3/15). In 3 patients, mitochondrial disease presented as adult-onset isolated dystonia. In comparison to healthy controls and mitochondrial disease patients without movement disorders, patients with hypo- and hyperkinetic movement disorders had significantly more cerebellar atrophy and an atrophy pattern predominantly involving cerebellar lobules VI and VII. Conclusion: This series provides clinical, genetic, volumetric imaging, and histologic data that indicate major involvement of the cerebellum in mitochondrial disease when it presents with hyper- and hypokinetic movement disorders. As a working hypothesis addressing the particular vulnerability of the cerebellum to energy deficiency, this adds substantially to the pathophysiological understanding of movement disorders in mitochondrial disease. Furthermore, it provides evidence that mitochondrial disease can present as adult-onset isolated dystonia. © 2017 International Parkinson and Movement Disorder Society.
Published:
2018-01
Title:
Overview of Approaches to Mitochondrial Disease Therapy
Authors:
Lehmann, Diana; McFarland, Robert
Abstract:
Mitochondrial respiratory chain diseases are the most prevalent group of inherited neurometabolic disorders and are clinically, biochemically, and genetically heterogeneous. They may present at any stage of life and often manifest with severe multisystem disease, although single organ involvement is characteristic of some conditions such as Leber hereditary optic neuropathy. As a result of these complexities, the diagnostic pathway is often challenging, so too is further advice, guidance, and therapy following diagnosis. Difficulties also occur with regard to genetic counseling, prognostic assessment, and treatment; there is still no cure or even agreed standards of treatment available for these debilitating diseases. Limited therapeutic options and a lack of curative treatment have led to physicians prescribing individual “trials of therapy” for which no evidence-based recommendations are available. However, new therapeutic options are the focus of active molecular genetic, biochemical, and clinical rese...
Published:
2018-01
Title:
Physiological mitochondrial fragmentation is a normal cardiac adaptation to increased energy demand
Authors:
Coronado, Michael; Fajardo, Giovanni; Nguyen, Kim; Zhao, Mingming; Kooiker, Kristina; Jung, Gwanghyun; Hu, Dong Qing; Reddy, Sushma; Sandoval, Erik; Stotland, Aleksandr; Gottlieb, Roberta A.; Bernstein, Daniel
Abstract:
Rationale: Mitochondria play a dual role in the heart, responsible for meeting energetic demands and regulating cell death. Paradigms have held that mitochondrial fssion and fragmentation are the result of pathological stresses, such as ischemia, are an indicator of poor mitochondrial health, and lead to mitophagy and cell death. However, recent studies demonstrate that inhibiting fssion also results in decreased mitochondrial function and cardiac impairment, suggesting that fssion is important for maintaining cardiac and mitochondrial bioenergetic homeostasis. Objective: The purpose of this study is to determine whether mitochondrial fssion and fragmentation can be an adaptive mechanism used by the heart to augment mitochondrial and cardiac function during a normal physiological stress, such as exercise. Methods and Results: We demonstrate a novel role for cardiac mitochondrial fssion as a normal adaptation to increased energetic demand. During submaximal exercise, physiological mitochondrial fragmentation results in enhanced, rather than impaired, mitochondrial function and is mediated, in part, by ß1-adrenergic receptor signaling. Similar to pathological fragmentation, physiological fragmentation is induced by activation of dynaminrelated protein 1; however, unlike pathological fragmentation, membrane potential is maintained and regulators of mitophagy are downregulated. Inhibition of fssion with P110, Mdivi-1 (mitochondrial division inhibitor), or in mice with cardiac-specifc dynamin-related protein 1 ablation signifcantly decreases exercise capacity. Conclusions: These fndings demonstrate the requirement for physiological mitochondrial fragmentation to meet the energetic demands of exercise, as well as providing additional support for the evolving conceptual framework, where mitochondrial fssion and fragmentation play a role in the balance between mitochondrial maintenance of normal physiology and response to disease.
Published:
2018-01
Title:
Suppression of microRNA-454 impedes the proliferation and invasion of prostate cancer cells by promoting N-myc downstream-regulated gene 2 and inhibiting WNT/β-catenin signaling
Authors:
Fu, Qiang; Gao, Yanyao; Yang, Fan; Mao, Tianci; Sun, Zhenye; Wang, He; Song, Bin; Li, Xin
Abstract:
MicroRNA-454 (miR-454) is emerging as critical regulator in tumorigenesis; it may function as an oncogene or a tumor suppressor. However, the role of miR-454 in prostate cancer remains unknown. In this study, we aimed to investigate the function and molecular mechanisms of miR-454 in prostate cancer. We found that miR-454 was highly expressed in prostate cancer tissues and cell lines (*p<0.05), as detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell counting kit-8 assay, colony formation assay and cell invasion assay showed that the inhibition of miR-454 significantly suppressed prostate cancer cell proliferation and invasion (*p<0.05), whereas the overexpression of miR-454 markedly promoted prostate cancer cell proliferation and invasion (*p<0.05). Bioinformatics analysis showed that N-myc downstream-regulated gene 2 (NDRG2), a well-known tumor suppressor, was identified as a potential target gene of miR-454. Dual-luciferase reporter assay showed that miR-454 directly targeted the 3'-untranslated region of NDRG2. RT-qPCR and western blot showed that miR-454 overexpression significantly decreased NDRG2 expression (*p<0.05), whereas miR-454 inhibition markedly promoted NDRG2 expression (*p<0.05). Spearman's correlation analysis showed that miR-454 expression was inversely correlated with NDRG2 expression in prostate cancer tissues (r=-0.8932; p<0.0001). Moreover, miR-454 inhibition significantly suppressed the protein expression of β-catenin (*p<0.05) and blocked the activation of WNT signaling (*p<0.05). In addition, small interfering RNA mediated NDRG2 knockdown significantly reversed the antitumor effect of miR-454 inhibition on prostate cancer cell proliferation and invasion (*p
Published:
2018-01
Title:
Treatable inherited rare movement disorders
Authors:
Jinnah, H. A.; Albanese, Alberto; Bhatia, Kailash P.; Cardoso, Francisco; Da Prat, Gustavo; de Koning, Tom J.; Espay, Alberto J.; Fung, Victor; Garcia-Ruiz, Pedro J.; Gershanik, Oscar; Jankovic, Joseph; Kaji, Ryuji; Kotschet, Katya; Marras, Connie; Miyasaki, Janis M.; Morgante, Francesca; Munchau, Alexander; Pal, Pramod Kumar; Rodriguez Oroz, Maria C.; Rodríguez-Violante, Mayela; Schöls, Ludger; Stamelou, Maria; Tijssen, Marina; Uribe Roca, Claudia; de la Cerda, Andres; Gatto, Emilia M.
Abstract:
© 2017 International Parkinson and Movement Disorder Society There are many rare movement disorders, and new ones are described every year. Because they are not well recognized, they often go undiagnosed for long periods of time. However, early diagnosis is becoming increasingly important. Rapid advances in our understanding of the biological mechanisms responsible for many rare disorders have enabled the development of specific treatments for some of them. Well-known historical examples include Wilson disease and dopa-responsive dystonia, for which specific and highly effective treatments have life-altering effects. In recent years, similarly specific and effective treatments have been developed for more than 30 rare inherited movement disorders. These treatments include specific medications, dietary changes, avoidance or management of certain triggers, enzyme replacement therapy, and others. This list of treatable rare movement disorders is likely to grow during the next few years because a number of additional promising treatments are actively being developed or evaluated in clinical trials. © 2017 International Parkinson and Movement Disorder Society.
Published:
2018-01
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