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Title:
Improvement in patient-reported sleep in type 2 diabetes and prediabetes participants receiving a continuous care intervention with nutritional ketosis
Authors:
Siegmann, Morgan J.; Athinarayanan, Shaminie J.; Hallberg, Sarah J.; McKenzie, Amy L.; Bhanpuri, Nasir H.; Campbell, Wayne W.; McCarter, James P.; Phinney, Stephen D.; Volek, Jeff S.; Van Dort, Christa J.
Abstract:
OBJECTIVE: Sleep disruption is frequently associated with type 2 diabetes (T2D) and hyperglycemia. We recently reported the effectiveness of a continuous care intervention (CCI) emphasizing nutritional ketosis for improving HbA1c, body weight and cardiovascular risk factors in T2D patients. The present study assessed the effect of this CCI approach on sleep quality using a subjective patient-reported sleep questionnaire. METHODS: A non-randomized, controlled longitudinal study; 262 T2D and 116 prediabetes patients enrolled in the CCI and 87 separately recruited T2D patients continued usual care (UC) treatment. Patients completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire. A PSQI score of >5 (scale 0 to 21) was used to identify poor sleepers. RESULTS: Global sleep quality improved in the CCI T2D (p < 0.001) and prediabetes (p < 0.001) patients after one year of intervention. Subjective sleep quality (component 1), sleep disturbance (component 5) and daytime dysfunction (component 7), also showed improvements in the CCI T2D (p < 0.01 for sleep quality and sleep disturbance; and p < 0.001 for daytime dysfunction) and prediabetes patients (p < 0.001 for all three components); compared to the UC T2D group after one year. The proportion of patients with poor sleep quality was significantly reduced after one year of CCI (T2D; from 68.3% at baseline to 56.5% at one year, p = 0.001 and prediabetes; from 77.9% at baseline to 48.7% at one year, p
Published:
2019
Title:
Influence of blue mussel (Mytilus edulis) intake on fatty acid composition in erythrocytes and plasma phospholipids and serum metabolites in women with rheumatoid arthritis
Authors:
Lindqvist, H.M.; Gjertsson, I.; Andersson, S.; Calder, P.C.; Bärebring, L.
Abstract:
Intake of blue mussels decreased disease activity in women with rheumatoid arthritis (RA) in the randomized cross-over MIRA (Mussels, inflammation and RA) trial. This study investigates potential causes of the decreased disease activity by analysing fatty acid composition in erythrocytes and plasma phospholipids and serum metabolites in samples from the participants of the MIRA trial. Twenty-three women completed the randomized 2 × 11-week cross-over dietary intervention, exchanging one cooked meal per day, 5 days a week, with a meal including 75 g blue mussels or 75 g meat. Fatty acid composition in erythrocytes and plasma and 1H Nuclear Magnetic Resonance (1H NMR) metabolomics data were analysed with multivariate data analysis. Orthogonal Projections to Latent Structures with Discriminant Analysis (OPLS-DA) and OPLS with effect projections (OPLS-EP) were performed to compare the two diets. The fatty acid profile in erythrocytes was different after intake of blue mussels compared to the control diet, and all samples were correctly classified to either the blue mussel diet or control diet. Changes following blue mussel intake included significant increases in omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at the group level but not for all individuals. The fatty acid profile in plasma phospholipids and 1H NMR serum metabolites did not differ significantly between the diets. To conclude, modelling fatty acids in erythrocytes may be a better biomarker for seafood intake than only EPA and DHA content. The change in fatty acid pattern in erythrocytes could be related to reduction in disease activity, although it cannot be excluded that other factors than omega-3 fatty acids potentiate the effect. © 2019 Elsevier Ltd
Published:
2019
Title:
Insulin action in the brain regulates mitochondrial stress responses and reduces diet-induced weight gain
Authors:
Wardelmann, Kristina; Blümel, Sabine; Rath, Michaela; Alfine, Eugenia; Chudoba, Chantal; Schell, Mareike; Cai, Weikang; Hauffe, Robert; Warnke, Kathrin; Flore, Tanina; Ritter, Katrin; Weiß, Jürgen; Kahn, C. Ronald; Kleinridders, André
Abstract:
OBJECTIVE: Insulin action in the brain controls metabolism and brain function, which is linked to proper mitochondrial function. Conversely, brain insulin resistance associates with mitochondrial stress and metabolic and neurodegenerative diseases. In the present study, we aimed to decipher the impact of hypothalamic insulin action on mitochondrial stress responses, function and metabolism. METHODS: To investigate the crosstalk of insulin action and mitochondrial stress responses (MSR), namely the mitochondrial unfolded protein response (UPRmt) and integrated stress response (ISR), qPCR, western blotting, and mitochondrial activity assays were performed. These methods were used to analyze the hypothalamic cell line CLU183 treated with insulin in the presence or absence of the insulin receptor as well as in mice fed a high fat diet (HFD) for three days and STZ-treated mice without or with insulin therapy. Intranasal insulin treatment was used to investigate the effect of acute brain insulin action on metabolism and mitochondrial stress responses. RESULTS: Acute HFD feeding reduces hypothalamic mitochondrial stress responsive gene expression of Atf4, Chop, Hsp60, Hsp10, ClpP, and Lonp1 in C57BL/6N mice. We show that insulin via ERK activation increases the expression of MSR genes in vitro as well as in the hypothalamus of streptozotocin-treated mice. This regulation propagates mitochondrial function by controlling mitochondrial proteostasis and prevents excessive autophagy under serum deprivation. Finally, short-term intranasal insulin treatment activates MSR gene expression in the hypothalamus of HFD-fed C57BL/6N mice and reduces food intake and body weight development. CONCLUSIONS: We define hypothalamic insulin action as a novel master regulator of MSR, ensuring proper mitochondrial function by controlling mitochondrial proteostasis and regulating metabolism.
Published:
2019
Title:
Integrative analysis of the intestinal metabolome of childhood asthma
Authors:
Lee-Sarwar, K.A.; Kelly, R.S.; Lasky-Su, J.; Zeiger, R.S.; O'Connor, G.T.; Sandel, M.T.; Bacharier, L.B.; Beigelman, A.; Laranjo, N.; Gold, D.R.; Weiss, S.T.; Litonjua, A.A.
Abstract:
Background: The intestinal metabolome reflects the biological consequences of diverse exposures and might provide insight into asthma pathophysiology. Objective: We sought to perform an untargeted integrative analysis of the intestinal metabolome of childhood asthma in this ancillary study of the Vitamin D Antenatal Asthma Reduction Trial. Methods: Metabolomic profiling was performed by using mass spectrometry on fecal samples collected from 361 three-year-old subjects. Adjusted logistic regression analyses identified metabolites and modules of highly correlated metabolites associated with asthma diagnosis by age 3 years. Sparse canonical correlation analysis identified associations relevant to asthma between the intestinal metabolome and other “omics”: the intestinal microbiome as measured by using 16S rRNA sequencing, the plasma metabolome as measured by using mass spectrometry, and diet as measured by using food frequency questionnaires. Results: Several intestinal metabolites were associated with asthma at age 3 years, including inverse associations between asthma and polyunsaturated fatty acids (adjusted logistic regression β = −6.3; 95% CI, −11.3 to −1.4; P = .01) and other lipids. Asthma-associated intestinal metabolites were significant mediators of the inverse relationship between exclusive breast-feeding for the first 4 months of life and asthma (P for indirect association = .04) and the positive association between a diet rich in meats and asthma (P = .03). Specific intestinal bacterial taxa, including the family Christensenellaceae, and plasma metabolites, including γ-tocopherol/β-tocopherol, were positively associated with asthma and asthma-associated intestinal metabolites. Conclusion: Integrative analyses revealed significant interrelationships between the intestinal metabolome and the intestinal microbiome, plasma metabolome, and diet in association with childhood asthma. These findings require replication in future studies. © 2019 American Academy of Allergy, Asthma & Immunology
Published:
2019
Title:
Integrative single-cell analysis
Authors:
Stuart, Tim; Satija, Rahul
Abstract:
The recent maturation of single-cell RNA sequencing (scRNA-seq) technologies has coincided with transformative new methods to profile genetic, epigenetic, spatial, proteomic and lineage information in individual cells. This provides unique opportunities, alongside computational challenges, for integrative methods that can jointly learn across multiple types of data. Integrated analysis can discover relationships across cellular modalities, learn a holistic representation of the cell state, and enable the pooling of data sets produced across individuals and technologies. In this Review, we discuss the recent advances in the collection and integration of different data types at single-cell resolution with a focus on the integration of gene expression data with other types of single-cell measurement.
Published:
2019
Title:
Intermittent parathyroid hormone 1–34 induces oxidation and deterioration of mineral and collagen quality in newly formed mandibular bone
Authors:
Yoshioka, Y.; Yamachika, E.; Nakanishi, M.; Ninomiya, T.; Akashi, S.; Kondo, S.; Moritani, N.; Kobayashi, Y.; Fujii, T.; Iida, S.
Abstract:
Intermittent parathyroid hormone (PTH) administration is known to promote bone healing after surgical procedures. However, the mechanism and influence of PTH on the mineral and collagen quality of the jaw are not well understood. Most studies have focused on analyzing the bone density and microstructure of the mandible, and have insufficiently investigated its mineral and collagen quality. Oxidative stress activates osteoclasts, produces advanced glycation end products, and worsens mineral and collagen quality. We hypothesized that PTH induces oxidation and affects the mineral and collagen quality of newly formed mandibular bone. To test this, we examined the mineral and collagen quality of newly formed mandibular bone in rats administered PTH, and analyzed serum after intermittent PTH administration to examine the degree of oxidation. PTH administration reduced mineralization and worsened mineral and collagen quality in newly formed bone. In addition, total anti-oxidant capacity in serum was significantly decreased and the oxidative-INDEX was increased among PTH-treated compared to vehicle-treated rats, indicating serum oxidation. In conclusion, intermittent administration of PTH reduced mineral and collagen quality in newly formed mandibular bone. This effect may have been induced by oxidation. © 2019, The Author(s).
Published:
2019
Title:
Journal Pre-proof Role of acupuncture in the treatment of insulin resistance: A systematic review and meta-analysis
Authors:
Wu, Liqun; Chen, Xiaokun; Liu, Yun; Lan, Jiao; Wu, Chunxiao; Li, Zhixing; Lu, Liming; Yi, Wei
Abstract:
of acupuncture in the treatment of insulin resistance: A systematic review and meta-analysis, Complementary Therapies in Clinical Practice (2019), doi: https://doi.org/10.1016/j.ctcp.2019.08.002. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Published:
2019
Title:
Ketogenic Diet and Microbiota: Friends or Enemies?
Authors:
Paoli, Antonio; Mancin, Laura; Bianco, Antonino; Thomas, Ewan; Mota, João Felipe; Piccini, Fabio
Abstract:
Over the last years, a growing body of evidence suggests that gut microbial communities play a fundamental role in many aspects of human health and diseases. The gut microbiota is a very dynamic entity influenced by environment and nutritional behaviors. Considering the influence of such a microbial community on human health and its multiple mechanisms of action as the production of bioactive compounds, pathogens protection, energy homeostasis, nutrients metabolism and regulation of immunity, establishing the influences of different nutritional approach is of pivotal importance. The very low carbohydrate ketogenic diet is a very popular dietary approach used for different aims: from weight loss to neurological diseases. The aim of this review is to dissect the complex interactions between ketogenic diet and gut microbiota and how this large network may influence human health.
Published:
2019
Title:
Ketogenic Diet: an Endocrinologist Perspective
Authors:
Kuchkuntla, Aravind Reddy; Shah, Meera; Velapati, Saketh; Gershuni, Victoria M.; Rajjo, Tamim; Nanda, Sanjeev; Hurt, Ryan T.; Mundi, Manpreet S.
Abstract:
PURPOSE OF REVIEW: Obesity and its related comorbidities make up a large part of healthcare expenditures. Despite a wide array of options for treatment of obesity, rates of sustained weight loss continue to be low, leading patients to seek alternative treatment options. Although the first medically utilized ketogenic diet was described nearly 100 years ago, it has made a resurgence as a treatment option for obesity. Despite increased popularity in the lay public and increased use of ketogenic dietary strategies for metabolic therapy, we are still beginning to unravel the metabolic impact of long-term dietary ketosis. RECENT FINDINGS: There are a number of recent trials that have highlighted the short- and long-term benefits of ketogenic diet on weight, glycemic control, and other endocrine functions including reproductive hormones. This review is a summary of available data on the effectiveness and durability of the ketogenic diet when compared to conventional interventions. Ketogenic dietary strategies may play a role in short-term improvement of important metabolic parameters with potential for long-term benefit. However, response may vary due to inter-individual ability to maintain long-term carbohydrate restriction.
Published:
2019
Title:
Letter by Ravnskov et al Regarding Article, "Long-Term Association of Low-Density Lipoprotein Cholesterol With Cardiovascular Mortality in Individuals at Low 10-Year Risk of Atherosclerotic Cardiovascular Disease: Results From the Cooper Center Longitudinal Study"
Authors:
Ravnskov, Uffe; Okuyama, Harumi; Sultan, Sherif
Abstract:
Published:
2019
Title:
Lipid findings from the Diabetes Education to Lower Insulin, Sugars, and Hunger (DELISH) Study
Authors:
Mason, Ashley E.; Saslow, Laura R.; Moran, Patricia J.; Kim, Sarah; Abousleiman, Hiba; Richler, Robert; Schleicher, Samantha; Goldman, Veronica M.; Hartman, Alison; Leung, Cindy; Hartogensis, Wendy; Hecht, Frederick M.
Abstract:
Background: A carbohydrate-restricted (CR) diet can improve glycemic control in people with type 2 diabetes mellitus (T2DM). There are concerns, however, that the high dietary fat content of CR diets can increase low-density lipoprotein cholesterol (LDL-C), thus increasing cardiovascular disease (CVD) risk. Quantifying CVD risk associated with changes in LDL-C in the context of CR diets is complicated by the fact that LDL-C reflects heterogeneous lipids. For example, small LDL particle number (sLDL-P) is more closely associated with CVD risk than is total LDL-C, and CR diets tend to decrease the proportion of sLDL-C in LDL-C, which standard lipid measures do not indicate. Advanced lipoprotein assays, such as nuclear magnetic resonance (NMR) testing, can subfractionate lipoproteins by size and density and may better depict the effects of CR diets on CVD risk. Methods: Adults (N = 58) with T2DM (n = 37 women; baseline HbA1c ≥ 6.5%) completed a 6-month group-based CR diet intervention. We obtained a standard lipid panel, advanced lipoprotein assays (NMR testing), and two 24-h diet recalls at baseline and post-intervention (6 months). Participants also completed home-based blood ketone testing (a biological index of dietary adherence) during the final five weeks of the intervention. Results: From baseline to post-intervention, participants had increased mean HDL-C, decreased triglycerides and triglyceride/HDL ratio, decreased mean sLDL-P, and increased LDL size, which reflect reductions in CVD risk (ps
Published:
2019
Title:
Lipidomic methodologies for biomarkers of chronic inflammation in nutritional research: ω-3 and ω-6 lipid mediators
Authors:
Dasilva, G.; Medina, I.
Abstract:
The evolutionary history of hominins has been characterized by significant dietary changes, which include the introduction of meat eating, cooking, and the changes associated with plant and animal domestication. The Western pattern diet has been linked with the onset of chronic inflammation, and serious health problems including obesity, metabolic syndrome, and cardiovascular diseases. Diets enriched with ω-3 marine PUFAs have revealed additional improvements in health status associated to a reduction of proinflammatory ω-3 and ω-6 lipid mediators. Lipid mediators are produced from enzymatic and non-enzymatic oxidation of PUFAs. Interest in better understanding the occurrence of these metabolites has increased exponentially as a result of the growing evidence of their role on inflammatory processes, control of the immune system, cell signaling, onset of metabolic diseases, or even cancer. The scope of this review has been to highlight the recent findings on: a) the formation of lipid mediators and their role in different inflammatory and metabolic conditions, b) the direct use of lipid mediators as antiinflammatory drugs or the potential of new drugs as a new therapeutic option for the synthesis of antiinflammatory or resolving lipid mediators and c) the impact of nutritional interventions to modulate lipid mediators synthesis towards antiinflammatory conditions. In a second part, we have summarized methodological approaches (Lipidomics) for the accurate analysis of lipid mediators. Although several techniques have been used, most authors preferred the combination of SPE with LC-MS. Advantages and disadvantages of each method are herein addressed, as well as the main LC-MS difficulties and challenges for the establishment of new biomarkers and standardization of experimental designs, and finally to deepen the study of mechanisms involved on the inflammatory response. © 2019 Elsevier Inc.
Published:
2019
Title:
Liquiritigenin Reduces Blood Glucose Level and Bone Adverse Effects in Hyperglycemic Adult Zebrafish
Authors:
Carnovali, M.; Luzi, L.; Terruzzi, I.; Banfi, G.; Mariotti, M.
Abstract:
Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia that induces other pathologies including diabetic retinopathy and bone disease. Adult Danio rerio (zebrafish) represents a powerful model to study both glucose and bone metabolism. Then, the aim of this study was to evaluate the effects of liquiritigenin (LTG) on blood glucose level and diabetes complications in hyperglycemic adult zebrafish. LTG is a flavonoid extracted from Glycyrrhiza glabra roots which possess important antioxidant, anti-inflammatory, and anti-diabetic properties. During four weeks of glucose treatment, LTG significantly prevented the onset of the hyperglycemia in adult zebrafish. Moreover, hyperglycemic fish showed increased advanced glycation end-products (AGEs) and parathormone levels whereas LTG completely prevented both of these metabolic alterations. Large bone-loss areas were found in the scales of glucose-treated fish whereas only small resorption lacunae were detected after glucose/LTG treatment. Biochemical and histological tartrate resistant acid phosphatase (TRAP) assays performed on explanted scales confirmed that LTG prevented the increase of osteoclastic activity in hyperglycemic fish. The osteoblastic alkaline phosphatase (ALP) activity was clearly lost in scales of glucose-treated fish whereas the co-treatment with LTG completely prevented such alteration. Gene expression analysis showed that LTG prevents the alteration in crucial bone regulatory genes. Our study confirmed that LTG is a very promising natural therapeutic approach for blood glucose lowering and to contrast the development of bone complications correlated to chronic hyperglycemia.
Published:
2019
Title:
Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-Year Non-randomized Clinical Trial
Authors:
Athinarayanan, Shaminie J.; Adams, Rebecca N.; Hallberg, Sarah J.; McKenzie, Amy L.; Bhanpuri, Nasir H.; Campbell, Wayne W.; Volek, Jeff S.; Phinney, Stephen D.; McCarter, James P.
Abstract:
Purpose: Studies on long-term sustainability of low-carbohydrate approaches to treat diabetes are limited. We previously reported the effectiveness of a novel digitally-monitored continuous care intervention (CCI) including nutritional ketosis in improving weight, glycemic outcomes, lipid, and liver marker changes at 1 year. Here, we assess the effects of the CCI at 2 years. Materials and methods: An open label, non-randomized, controlled study with 262 and 87 participants with T2D were enrolled in the CCI and usual care (UC) groups, respectively. Primary outcomes were retention, glycemic control, and weight changes at 2 years. Secondary outcomes included changes in body composition, liver, cardiovascular, kidney, thyroid and inflammatory markers, diabetes medication use and disease status. Results: Reductions from baseline to 2 years in the CCI group resulting from intent-to-treat analyses included: HbA1c, fasting glucose, fasting insulin, weight, systolic blood pressure, diastolic blood pressure, triglycerides, and liver alanine transaminase, and HDL-C increased. Spine bone mineral density in the CCI group was unchanged. Use of any glycemic control medication (excluding metformin) among CCI participants declined (from 55.7 to 26.8%) including insulin (-62%) and sulfonylureas (-100%). The UC group had no changes in these parameters (except uric acid and anion gap) or diabetes medication use. There was also resolution of diabetes (reversal, 53.5%; remission, 17.6%) in the CCI group but not in UC. All the reported improvements had p
Published:
2019
Title:
Long-Term Local Injection of RAGE-Aptamer Suppresses the Growth of Malignant Melanoma in Nude Mice
Authors:
Nakamura, Nobutaka; Matsui, Takanori; Nishino, Yuri; Sotokawauchi, Ami; Higashimoto, Yuichiro; Yamagishi, Sho-ichi
Abstract:
Accumulating evidence has suggested the pathological role of advanced glycation end products (AGEs) and their receptor RAGE axis in aging-associated disorders, including cancers. In this study, we examined the effects of local injection of RAGE-aptamer adjacent to the tumor on G361 melanoma growth in nude mice. We further investigated the effects of RAGE-aptamer on oxidative stress generation, RAGE, vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1) gene expression in Nε-(carboxymethyl)lysine (CML)-exposed G361 melanoma cells in vitro. Local injection of RAGE-aptamer adjacent to the tumor dramatically decreased the growth of G361 melanoma in nude mice, which was associated with reduced expression of CML, RAGE, nitrotyrosine, VEGF, CD31, and von Willebrand factor, markers of endothelial cells in G361 tumors. Furthermore, RAGE-aptamer inhibited the binding of CML to V-domain of RAGE and blocked the CML-induced increases in oxidative stress generation, RAGE, VEGF, and MCP-1 mRNA levels in G361 melanoma cells. Our present findings suggest that long-term local injection of RAGE-aptamer adjacent to the tumor could inhibit melanoma growth in nude mice partly by suppressing tumor angiogenesis via blockade of the CML-RAGE interaction. Local injection of RAGE-aptamer may be a feasible therapeutic tool for the treatment of malignant melanoma.
Published:
2019
Title:
Low-phytate wholegrain bread instead of high-phytate wholegrain bread in a total diet context did not improve iron status of healthy Swedish females: a 12-week, randomized, parallel-design intervention study
Authors:
Hoppe, M.; Ross, A.B.; Svelander, C.; Sandberg, A.-S.; Hulthén, L.
Abstract:
Purpose: To investigate the effects of eating wholegrain rye bread with high or low amounts of phytate on iron status in women under free-living conditions. Methods: In this 12-week, randomized, parallel-design intervention study, 102 females were allocated into two groups, a high-phytate-bread group or a low-phytate-bread group. These two groups were administered: 200 g of blanched wholegrain rye bread/day, or 200 g dephytinized wholegrain rye bread/day. The bread was administered in addition to their habitual daily diet. Iron status biomarkers and plasma alkylresorcinols were analyzed at baseline and post-intervention. Results: Fifty-five females completed the study. In the high-phytate-bread group (n = 31) there was no change in any of the iron status biomarkers after 12 weeks of intervention (p > 0.05). In the low-phytate bread group (n = 24) there were significant decreases in both ferritin (mean = 12%; from 32 ± 7 to 27 ± 6 µg/L, geometric mean ± SEM, p < 0.018) and total body iron (mean = 12%; from 6.9 ± 1.4 to 5.4 ± 1.1 mg/kg, p
Published:
2019
Title:
Meditation interventions among heart failure patients: An integrative review
Authors:
Viveiros, Jennifer; Chamberlain, Brianna; O'Hare, Aminda; Sethares, Kristen A
Abstract:
BACKGROUND: There has been growing interest in meditation techniques as an intervention in chronic disease populations. Little is known of the effect meditation practice has on outcomes among patients with heart failure., PURPOSE: To identify and examine current literature on meditation interventions on heart failure outcomes., METHOD: The review utilized methods described by Whittemore and Knafl. Three electronic databases were searched through March 2018. Terms used were "mindfulness OR meditation" and "heart failure" in combination, generating 58 articles after duplicates were removed. After inclusion and exclusion criteria were applied, six studies qualified for review, including four articles with samples from the United States and two with samples from Brazil and Sweden, respectively., RESULTS: Among the six studies in the final sample, the total number of participants was 320 heart failure patients. Interventional design and length varied among the studies, and 20 different dependent variables were identified. This study distinguished four categories of outcome measures with significant findings: psychosocial, biophysical, quality of life and heart failure symptom burden. Compared with controls meditation practice significantly improved depression (p\textless.05), social support (p\textless.05), biophysical factors and quality of life (p\textless.05), in addition to reducing heart failure symptom burden. Across-study comparisons were limited due to variation in intervention definitions and designs. Additionally, the intervention dose and reporting method varied, limiting comparisons. The sample size in five out of six studies was fewer than 50 participants. Over 20 different measures were used across the six studies to measure outcome variables., CONCLUSION: Meditation may offer a patient-driven practice to reduce heart failure symptoms as well as improve psychosocial wellness and quality of life. Future research among heart failure patients should include the following: rigorous definition of meditation interventions, consistency in intervention characteristics, larger controlled trials, and standardized outcome instruments.
Published:
2019
Title:
Mediterranean-style diet in pregnant women with metabolic risk factors (ESTEEM): A pragmatic multicentre randomised trial
Authors:
H. Al Wattar, B.; Dodds, J.; Placzek, A.; Beresford, L.; Spyreli, E.; Moore, A.; Gonzalez Carreras, F.J.; Austin, F.; Murugesu, N.; Roseboom, T.J.; Bes-Rastrollo, M.; Hitman, G.A.; Hooper, R.; Khan, K.S.; Thangaratinam, S.; ESTEEM, study group
Abstract:
Background: Pregnant women with metabolic risk factors are at high risk of complications. We aimed to assess whether a Mediterranean-style diet reduces adverse pregnancy outcomes in high-risk women. Methods and findings: We conducted a multicentre randomised trial in 5 maternity units (4 in London and 1 in Birmingham) between 12 September 2014 and 29 February 2016. We randomised inner-city pregnant women with metabolic risk factors (obesity, chronic hypertension, or hypertriglyceridaemia) to a Mediterranean-style diet with high intake of nuts, extra virgin olive oil, fruits, vegetables, nonrefined grains, and legumes; moderate to high consumption of fish; low to moderate intake of poultry and dairy products; low intake of red and processed meat; and avoidance of sugary drinks, fast food, and food rich in animal fat versus usual care. Participants received individualised dietary advice at 18, 20, and 28 weeks’ gestation. The primary endpoints were composite maternal (gestational diabetes or preeclampsia) and composite offspring (stillbirth, small for gestational age, or admission to neonatal care unit) outcomes prioritised by a Delphi survey. We used an intention-to-treat (ITT) analysis with multivariable models and identified the stratification variables and prognostic factors a priori. We screened 7,950 and randomised 1,252 women. Baseline data were available for 593 women in the intervention (93.3% follow-up, 553/593) and 612 in the control (95.6% follow-up, 585/612) groups. Over a quarter of randomised women were primigravida (330/1,205; 27%), 60% (729/1,205) were of Black or Asian ethnicity, and 69% (836/1,205) were obese. Women in the intervention arm consumed more nuts (70.1% versus 22.9%; adjusted odds ratio [aOR] 6.8, 95% confidence interval [CI] 4.3–10.6, p ≤ 0.001) and extra virgin olive oil (93.2% versus 49.0%; aOR 32.2, 95% CI 16.0–64.6, p ≤ 0.001) than controls; increased their intake of fish (p < 0.001), white meat (p < 0.001), and pulses (p = 0.05); and reduced their intake of red meat (p < 0.001), butter, margarine, and cream (p < 0.001). There was no significant reduction in the composite maternal (22.8% versus 28.6%; aOR 0.76, 95% CI 0.56–1.03, p = 0.08) or composite offspring (17.3% versus 20.9%; aOR 0.79, 95% CI 0.58–1.08, p = 0.14) outcomes. There was an apparent reduction in the odds of gestational diabetes by 35% (aOR 0.65, 95% CI 0.47–0.91, p = 0.01) but not in other individual components of the composite outcomes. Mothers gained less gestational weight (mean 6.8 versus 8.3 kg; adjusted difference −1.2 Kg, 95% CI −2.2 to −0.2, p = 0.03) with intervention versus control. There was no difference in any of the other maternal and offspring complications between both groups. When we pooled findings from the Effect of Simple, Targeted Diet in Pregnant Women With Metabolic Risk Factors on Pregnancy Outcomes (ESTEEM) trial with similar trials using random effects meta-analysis, we observed a significant reduction in gestational diabetes (odds ratio [OR] 0.67, 95% CI 0.53–0.84, I2 = 0%), with no heterogeneity (2 trials, 2,397 women). The study’s limitations include the use of participant reported tools for adherence to the intervention instead of objective biomarkers. Conclusions: A simple, individualised, Mediterranean-style diet in pregnancy did not reduce the overall risk of adverse maternal and offspring complications but has the potential to reduce gestational weight gain and the risk of gestational diabetes. Trial registration: ClinicalTrials.gov NCT02218931. © 2019 H. Al Wattar et al.
Published:
2019
Title:
Metabolic and Inflammatory Effects of an ω-3 Fatty Acid–Based Eucaloric Ketogenic Diet in Mice With Endotoxemia
Authors:
Anez‐Bustillos, Lorenzo; Dao, Duy T.; Finkelstein, Adam; Pan, Amy; Cho, Bennet S.; Mitchell, Paul D.; Gura, Kathleen M.; Bistrian, Bruce R.; Puder, Mark
Abstract:
Background Dietary strategies can aid in the management of critically ill patients. Very-low-carbohydrate diets have been shown to improve glucose control and the inflammatory response. We aimed to determine the effects of a eucaloric ketogenic diet (EKD) enriched with ω-3 fatty acids (O3KD) on glucose levels and inflammation in mice with endotoxemia. Methods Adult mice were fed 1 of 3 diets (control diet [CD], EKD, or O3KD). After 4 weeks, each group received saline or Escherichia coli lipopolysaccharide (LPS) (5 mg/kg) intraperitoneally during the postprandial (PPP) or postabsorptive (PAP) periods. Blood glucose was measured at 0, 15, 30, 60, 90, 120, 180, and 240 minutes. Serum tumor necrosis factor (TNF)-α and interleukin (IL) 6 were measured by enzyme-linked immunosorbent assay. Distribution of serum fatty acids was determined by gas liquid chromatography. Hepatic expression of genes involved in inflammation, as well as glucose and lipid metabolism, were determined by quantitative polymerase chain reaction. Results During the PPP, glucose curves were comparable among the experimental groups. During the PAP, EKD showed a more pronounced increase in glucose levels at the first hour after LPS challenge compared with the CD-LPS group. During the PAP, IL6 was lower in O3KD-LPS compared with CD-LPS and EKD-LPS groups. These differences disappeared in the PPP. Similarly, TNF-α was lower in the O3KD-LPS group compared with the EKD-LPS group. The O3KD significantly increased the serum levels of the ω-3 eicosapentaenoic and docosahexaenoic acids and decreased the ω-6 arachidonic acid. Conclusion An O3KD leads to reduced inflammation and maintains glucose homeostasis in mice with endotoxemia.
Published:
2019
Title:
Metabolic rewiring of macrophages by CpG potentiates clearance of cancer cells and overcomes tumor-expressed CD47-mediated 'don't-eat-me' signal
Authors:
Liu, Mingen; O'Connor, Roddy S.; Trefely, Sophie; Graham, Kathleen; Snyder, Nathaniel W.; Beatty, Gregory L.
Abstract:
Macrophages enforce antitumor immunity by engulfing and killing tumor cells. Although these functions are determined by a balance of stimulatory and inhibitory signals, the role of macrophage metabolism is unknown. Here, we study the capacity of macrophages to circumvent inhibitory activity mediated by CD47 on cancer cells. We show that stimulation with a CpG oligodeoxynucleotide, a Toll-like receptor 9 agonist, evokes changes in the central carbon metabolism of macrophages that enable antitumor activity, including engulfment of CD47+ cancer cells. CpG activation engenders a metabolic state that requires fatty acid oxidation and shunting of tricarboxylic acid cycle intermediates for de novo lipid biosynthesis. This integration of metabolic inputs is underpinned by carnitine palmitoyltransferase 1A and adenosine tri-phosphate citrate lyase, which, together, impart macrophages with antitumor potential capable of overcoming inhibitory CD47 on cancer cells. Our findings identify central carbon metabolism to be a novel determinant and potential therapeutic target for stimulating antitumor activity by macrophages.
Published:
2019
Title:
Metabolomics in the Development and Progression of Dementia: A Systematic Review
Authors:
Jiang, Yanfeng; Zhu, Zhen; Shi, Jie; An, Yanpeng; Zhang, Kexun; Wang, Yingzhe; Li, Shuyuan; Jin, Li; Ye, Weimin; Cui, Mei; Chen, Xingdong
Abstract:
Dementia has become a major global public health challenge with a heavy economic burden. It is urgently necessary to understand dementia pathogenesis and to identify biomarkers predicting risk of dementia in the preclinical stage for prevention, monitoring, and treatment. Metabolomics provides a novel approach for the identification of biomarkers of dementia. This systematic review aimed to examine and summarize recent retrospective cohort human studies assessing circulating metabolite markers, detected using high-throughput metabolomics, in the context of disease progression to dementia, including incident mild cognitive impairment, all-cause dementia, and cognitive decline. We systematically searched the PubMed, Embase, and Cochrane databases for retrospective cohort human studies assessing associations between blood (plasma or serum) metabolomics profile and cognitive decline and risk of dementia from inception through October 15, 2018. We identified 16 studies reporting circulating metabolites and risk of dementia, and six regarding cognitive performance change. Concentrations of several blood metabolites, including lipids (higher phosphatidylcholines, sphingomyelins, and lysophophatidylcholine, and lower docosahexaenoic acid and high-density lipoprotein subfractions), amino acids (lower branched-chain amino acids, creatinine, and taurine, and higher glutamate, glutamine, and anthranilic acid), and steroids were associated with cognitive decline and the incidence or progression of dementia. Circulating metabolites appear to be associated with the risk of dementia. Metabolomics could be a promising tool in dementia biomarker discovery. However, standardization and consensus guidelines for study design and analytical techniques require future development.
Published:
2019
Title:
Metabolomics-Based Dietary Biomarkers in Nutritional Epidemiology-Current Status and Future Opportunities
Authors:
Brennan, Lorraine; Hu, Frank B.
Abstract:
The application of metabolomics in nutrition epidemiology holds great promise and there is a high expectation that it will play a leading role in deciphering the interactions between diet and health. However, while significant progress has been made in the identification of putative biomarkers, more work is needed to address the use of the biomarkers in dietary assessment. The aim of this review is to critically evaluate progress in these areas and to identify challenges that need to be addressed going forward. The notable applications of dietary biomarkers in nutritional epidemiology include 1) determination of food intake based on biomarkers levels and calibration equations from feeding studies, 2) classification of individuals into dietary patterns based on the urinary metabolic profile, and 3) application of metabolome wide-association studies. Further work is needed to address some specific challenges to enable biomarkers to reach their full potential.
Published:
2019
Title:
Methylglyoxal, a glycolysis metabolite, triggers metastasis through MEK/ERK/SMAD1 pathway activation in breast cancer
Authors:
Nokin, Marie-Julie; Bellier, Justine; Durieux, Florence; Peulen, Olivier; Rademaker, Gilles; Gabriel, Maude; Monseur, Christine; Charloteaux, Benoit; Verbeke, Lieven; van Laere, Steven; Roncarati, Patrick; Herfs, Michael; Lambert, Charles; Scheijen, Jean; Schalkwijk, Casper; Colige, Alain; Caers, Jo; Delvenne, Philippe; Turtoi, Andrei; Castronovo, Vincent; Bellahcène, Akeila
Abstract:
Background Elevated aerobic glycolysis rate is a biochemical alteration associated with malignant transformation and cancer progression. This metabolic shift unavoidably generates methylglyoxal (MG), a potent inducer of dicarbonyl stress through the formation of advanced glycation end products (AGEs). We have previously shown that the silencing of glyoxalase 1 (GLO1), the main MG detoxifying enzyme, generates endogenous dicarbonyl stress resulting in enhanced growth and metastasis in vivo. However, the molecular mechanisms through which MG stress promotes metastasis development remain to be unveiled. Methods In this study, we used RNA sequencing analysis to investigate gene-expression profiling of GLO1-depleted breast cancer cells and we validated the regulated expression of selected genes of interest by RT-qPCR. Using in vitro and in vivo assays, we demonstrated the acquisition of a pro-metastatic phenotype related to dicarbonyl stress in MDA-MB-231, MDA-MB-468 and MCF7 breast cancer cellular models. Hyperactivation of MEK/ERK/SMAD1 pathway was evidenced using western blotting upon endogenous MG stress and exogenous MG treatment conditions. MEK and SMAD1 regulation of MG pro-metastatic signature genes in breast cancer cells was demonstrated by RT-qPCR. Results High-throughput transcriptome profiling of GLO1-depleted breast cancer cells highlighted a pro-metastatic signature that establishes novel connections between MG dicarbonyl stress, extracellular matrix (ECM) remodeling by neoplastic cells and enhanced cell migration. Mechanistically, we showed that these metastasis-related processes are functionally linked to MEK/ERK/SMAD1 cascade activation in breast cancer cells. We showed that sustained MEK/ERK activation in GLO1-depleted cells notably occurred through the down-regulation of the expression of dual specificity phosphatases in MG-stressed breast cancer cells. The use of carnosine and aminoguanidine, two potent MG scavengers, reversed MG stress effects in in vitro and in vivo experimental settings. Conclusions These results uncover for the first time the key role of MG dicarbonyl stress in the induction of ECM remodeling and the activation of migratory signaling pathways, both in favor of enhanced metastatic dissemination of breast cancer cells. Importantly, the efficient inhibition of mitogen-activated protein kinase (MAPK) signaling using MG scavengers further emphasizes the need to investigate their therapeutic potential across different malignancies. Electronic supplementary material The online version of this article (10.1186/s13058-018-1095-7) contains supplementary material, which is available to authorized users.
Published:
2019
Title:
Mito-Nuclear Communication by Mitochondrial Metabolites and Its Regulation by B-Vitamins
Authors:
Janssen, Joëlle J. E.; Grefte, Sander; Keijer, Jaap; de Boer, Vincent C. J.
Abstract:
Mitochondria are cellular organelles that control metabolic homeostasis and ATP generation, but also play an important role in other processes, like cell death decisions and immune signaling. Mitochondria produce a diverse array of metabolites that act in the mitochondria itself, but also function as signaling molecules to other parts of the cell. Communication of mitochondria with the nucleus by metabolites that are produced by the mitochondria provides the cells with a dynamic regulatory system that is able to respond to changing metabolic conditions. Dysregulation of the interplay between mitochondrial metabolites and the nucleus has been shown to play a role in disease etiology, such as cancer and type II diabetes. Multiple recent studies emphasize the crucial role of nutritional cofactors in regulating these metabolic networks. Since B-vitamins directly regulate mitochondrial metabolism, understanding the role of B-vitamins in mito-nuclear communication is relevant for therapeutic applications and optimal dietary lifestyle. In this review, we will highlight emerging concepts in mito-nuclear communication and will describe the role of B-vitamins in mitochondrial metabolite-mediated nuclear signaling.
Published:
2019
Title:
Mitochondrial Degeneration, Depletion of NADH, and Oxidative Stress Decrease Color Stability of Wet-Aged Beef Longissimus Steaks
Authors:
Mitacek, R.M.; Ke, Y.; Prenni, J.E.; Jadeja, R.; VanOverbeke, D.L.; Mafi, G.G.; Ramanathan, R.
Abstract:
Interrelationship between mitochondria and myoglobin function influence beef color. NADH level in postmortem muscle is an important determinant of mitochondrial activity and metmyoglobin reduction. Increased aging time promotes discoloration of steaks; however, the mechanism of this effect is not clear. The objective was to characterize the role of wet-aging in beef longissimus lumborum muscle mitochondrial function and to characterize the global metabolome to determine the mechanism of that can regenerate NADH. Beef longissimus lumborum muscles were randomly assigned to 3, 7, 14, 21, and 28 days aging periods. Surface color, biochemical, mitochondrial, and metabolite profiles were determined at each aging period and at the end of 6-day display. During 6-day display, sections aged for 28 days had 30.4% decrease in redness than sections aged for 3 days. Aging time decreased (P <0.05) muscle oxygen consumption, mitochondrial protein content, and antioxidant capacity. Metabolites such as fumaric acid, creatinine, and fructose, that can take part in glycolytic/TCA cycle and regenerate NADH decreased (P <0.05) with aging and display time. In support, NADH levels also decreased (P
Published:
2019
Title:
Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease
Authors:
Fang, Evandro F.; Hou, Yujun; Palikaras, Konstantinos; Adriaanse, Bryan A.; Kerr, Jesse S.; Yang, Beimeng; Lautrup, Sofie; Hasan-Olive, Md Mahdi; Caponio, Domenica; Dan, Xiuli; Rocktäschel, Paula; Croteau, Deborah L.; Akbari, Mansour; Greig, Nigel H.; Fladby, Tormod; Nilsen, Hilde; Cader, M. Zameel; Mattson, Mark P.; Tavernarakis, Nektarios; Bohr, Vilhelm A.
Abstract:
Accumulation of damaged mitochondria is a hallmark of aging and age-related neurodegeneration, including Alzheimer's disease (AD). The molecular mechanisms of impaired mitochondrial homeostasis in AD are being investigated. Here we provide evidence that mitophagy is impaired in the hippocampus of AD patients, in induced pluripotent stem cell-derived human AD neurons, and in animal AD models. In both amyloid-β (Aβ) and tau Caenorhabditis elegans models of AD, mitophagy stimulation (through NAD+ supplementation, urolithin A, and actinonin) reverses memory impairment through PINK-1 (PTEN-induced kinase-1)-, PDR-1 (Parkinson's disease-related-1; parkin)-, or DCT-1 (DAF-16/FOXO-controlled germline-tumor affecting-1)-dependent pathways. Mitophagy diminishes insoluble Aβ1-42 and Aβ1-40 and prevents cognitive impairment in an APP/PS1 mouse model through microglial phagocytosis of extracellular Aβ plaques and suppression of neuroinflammation. Mitophagy enhancement abolishes AD-related tau hyperphosphorylation in human neuronal cells and reverses memory impairment in transgenic tau nematodes and mice. Our findings suggest that impaired removal of defective mitochondria is a pivotal event in AD pathogenesis and that mitophagy represents a potential therapeutic intervention.
Published:
2019
Title:
Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report
Authors:
Evert, Alison B.; Dennison, Michelle; Gardner, Christopher D.; Garvey, W. Timothy; Lau, Ka Hei Karen; MacLeod, Janice; Mitri, Joanna; Pereira, Raquel F.; Rawlings, Kelly; Robinson, Shamera; Saslow, Laura; Uelmen, Sacha; Urbanski, Patricia B.; Yancy, William S.
Abstract:
Published:
2019
Title:
Olfactory connectivity mediates sleep-dependent food choices in humans
Authors:
Bhutani, Surabhi; Howard, James D; Reynolds, Rachel; Zee, Phyllis C; Gottfried, Jay; Kahnt, Thorsten
Abstract:
\textlessp\textgreaterSleep deprivation has marked effects on food intake, shifting food choices toward energy-dense options. Here we test the hypothesis that neural processing in central olfactory circuits, in tandem with the endocannabinoid system (ECS), plays a key role in mediating this relationship. We combined a partial sleep-deprivation protocol, pattern-based olfactory neuroimaging, and ad libitum food intake to test how central olfactory mechanisms alter food intake after sleep deprivation. We found that sleep restriction increased levels of the ECS compound 2-oleoylglycerol (2-OG), enhanced encoding of food odors in piriform cortex, and shifted food choices toward energy-dense food items. Importantly, the relationship between changes in 2-OG and food choices was formally mediated by odor-evoked connectivity between the piriform cortex and insula, a region involved in integrating feeding-related signals. These findings describe a potential neurobiological pathway by which state-dependent changes in the ECS may modulate chemosensory processing to regulate food choices.\textless/p\textgreater
Published:
2019
Title:
Our Blog How Ketones Can Combat Alzheimer ' s Replacing Glucose with Ketones to Combat Alzheimer ' s
Authors:
Blog, Our
Abstract:
Published:
2019
Title:
Patterns of Red and Processed Meat Consumption and Risk for All-Cause Mortality and Cardiometabolic Outcomes A Systematic Review and Meta-analysis of Cohort Studies
Authors:
Zeraatkar, Dena; Han, Mi Ah; Guyatt, Gordon H; Vernooij, Robin W M; Dib, Regina El; Cheung, Kevin; Milio, Kirolos; Zworth, Max; Bartoszko, Jessica J; Valli, Claudia; Lee, Yung; Zajac, Joanna; Prokop-dorner, Anna; Lo, Calvin; Bala, Malgorzata M; Alonso-coello, Pablo; Hanna, Steven E; Johnston, Bradley C
Abstract:
Published:
2019
Title:
Periprostatic Adipose Tissue Favors Prostate Cancer Cell Invasion in an Obesity-Dependent Manner: Role of Oxidative Stress
Authors:
Laurent, Victor; Toulet, Aurélie; Attané, Camille; Milhas, Delphine; Dauvillier, Stéphanie; Zaidi, Falek; Clement, Emily; Cinato, Mathieu; Le Gonidec, Sophie; Guérard, Adrien; Lehuédé, Camille; Garandeau, David; Nieto, Laurence; Renaud-Gabardos, Edith; Prats, Anne-Catherine; Valet, Philippe; Malavaud, Bernard; Muller, Catherine
Abstract:
Prostate gland is surrounded by periprostatic adipose tissue (PPAT), which is increasingly believed to play a paracrine role in prostate cancer progression. Our previous work demonstrates that adipocytes promote homing of prostate cancer cells to PPAT and that this effect is upregulated by obesity. Here, we show that once tumor cells have invaded PPAT (mimicked by an in vitro model of coculture), they establish a bidirectional crosstalk with adipocytes, which promotes tumor cell invasion. Indeed, tumor cells induce adipocyte lipolysis and the free fatty acids (FFA) released are taken up and stored by tumor cells. Incubation with exogenous lipids also stimulates tumor cell invasion, underlining the importance of lipid transfer in prostate cancer aggressiveness. Transferred FFAs (after coculture or exogenous lipid treatment) stimulate the expression of one isoform of the pro-oxidant enzyme NADPH oxidase, NOX5. NOX5 increases intracellular reactive oxygen species (ROS) that, in turn, activate a HIF1/MMP14 pathway, which is responsible for the increased tumor cell invasion. In obesity, tumor-surrounding adipocytes are more prone to activate the depicted signaling pathway and to induce tumor invasion. Finally, the expression of NOX5 and MMP14 is upregulated at the invasive front of human tumors where cancer cells are in close proximity to adipocytes and this process is amplified in obese patients, underlining the clinical relevance of our results. IMPLICATIONS: Our work emphasizes the key role of adjacent PPAT in prostate cancer dissemination and proposes new molecular targets for the treatment of obese patients exhibiting aggressive diseases.
Published:
2019
Title:
Physiological Effects of Dietary Amino Acids on Gut Health and Functions of Swine
Authors:
Yang, Zhongyue; Liao, Shengfa F.
Abstract:
Gut health has significant implications for swine overall health status and nutrient utilization, due to its various functions including digestion and absorption of nutrients, secretion of mucins and immunoglobulins, and selective barrier protection against harmful antigens and pathogens. Both the basic anatomical structure of the gut (such as epithelial cells) and its luminal microbiota play important roles for maintaining gut health and functions. The interactions between epithelial cells and luminal microbiota have significant impact on host nutrition and health through the metabolism of dietary components. Amino acids, which are major nutrients for pigs, are not only obligatory for maintaining the intestinal mucosal mass and integrity, but also for supporting the growth of microorganisms in the gut. Dietary amino acids are the major fuel of the small intestinal mucosa. Particularly, glutamate, glutamine, and aspartate are the major oxidative fuel of the intestine. Emerging evidence shows that arginine activates the mTOR signaling pathway in the small intestine. Utilization of glycine by the small intestinal mucosa to synthesize glutathione is a very important physiological pathway, and the role of glycine as a powerful cytoprotectant has also been recognized. The major end products of methionine and cysteine metabolism are glutathione, homocysteine and taurine, which play important roles in the intestinal immune and anti-oxidative responses. Threonine is highly utilized by the gut and is particularly important for mucin synthesis and maintenance of gut barrier integrity. Moreover, either a deficiency or an excess of dietary threonine can reduce the synthesis of intestinal mucosal proteins and mucins in young pigs. Various new functions of amino acids on gut health and functions have been discovered in recent years. Thus, this review is to provide some up-to-date knowledge for industry application of dietary amino acids in order to enhance swine gut health and functions, and also it is to provide a comprehensive reference for further scientific research in this regard.
Published:
2019
Title:
Pitfalls of clinical exome and gene panel testing: alternative transcripts
Authors:
Bodian, Dale L.; Kothiyal, Prachi; Hauser, Natalie S.
Abstract:
PURPOSE: Clinical exome and gene panel testing can provide molecular diagnoses for patients with rare Mendelian disorders, but for many patients these tests are nonexplanatory. We investigated whether interrogation of alternative transcripts in known disease genes could provide answers for additional patients. METHODS: We integrated alternative transcripts for known neonatal epilepsy genes with RNA-Seq data to identify brain-expressed coding regions that are not evaluated by popular neonatal epilepsy clinical gene panel and exome tests. RESULTS: We found brain-expressed alternative coding regions in 89 (30%) of 292 neonatal epilepsy genes. The 147 regions encompass 15,713 bases that are noncoding in the primary transcripts analyzed by the clinical tests. Alternative coding regions from at least 5 genes carry reported pathogenic variants. Three candidate variants in these regions were identified in public exome data from 337 epilepsy patients. Incorporating alternative transcripts into the analysis of neonatal epilepsy genes in 44 patient genomes identified the pathogenic variant for the epilepsy case and 2 variants of uncertain significance (VUS) among the 43 control cases. CONCLUSION: Assessment of alternative transcripts in exon-based clinical genetic tests, including gene panel, exome, and genome sequencing, may provide diagnoses for patients for whom standard testing is unrevealing, without introducing many VUS.
Published:
2019
Title:
Plasma, urine, and adipose tissue biomarkers of dietary intake differ between vegetarian and non-vegetarian diet groups in the Adventist Health Study-2
Authors:
Miles, F.L.; Lloren, J.I.C.; Haddad, E.; Jaceldo-Siegl, K.; Knutsen, S.; Sabate, J.; Fraser, G.E.
Abstract:
Background: Differences in food composition, nutrient intake, and various health outcomes have been reported for vegetarians and non-vegetarians in the Adventist Health Study-2 (AHS-2) cohort. Objective: We sought to determine whether biomarkers of dietary intake also differed between individuals classified as vegetarian (vegan, lacto-ovo-vegetarian, pesco-vegetarian, semi-vegetarian) and non-vegetarians based on patterns of consumption of meat, dairy, and eggs. Methods: Fasting plasma, overnight urine, and adipose tissue samples were collected from a representative subset of AHS-2 participants classified into 5 diet groups (vegan, lacto-ovo-vegetarian, pesco-vegetarian, semi-vegetarian, non-vegetarian) who also completed food-frequency questionnaires. Diet-related biomarkers including carotenoids, isoflavones, enterolactone, saturated and polyunsaturated fatty acids, and vitamins were analyzed in 840 male and female participants. Multiple linear regression was used to examine the association between diet pattern and biomarker abundance, comparing each of 4 vegetarian dietary groups to non-vegetarians, and adjusted mean values were calculated. Bonferroni correction was applied to control for multiple testing. Results: Vegans had higher plasma total carotenoid concentrations (1.6-fold, P < 0.0001), and higher excretion of urinary isoflavones (6-fold, P < 0.0001) and enterolactone (4.4-fold) compared with non-vegetarians. Vegans had lower relative abundance of saturated fatty acids including myristic, pentadecanoic, palmitic, and stearic acids (P < 0.0001). Vegans had higher linoleic acid (18:2ω-6) relative to non-vegetarians (23.3% compared with 19.1%) (P < 0.0001), and a higher proportion of total ω-3 fatty acids (2.1% compared with 1.6%) (P < 0.0001). Results overall were similar but less robust for lacto-ovo- and pesco-vegetarians. 1-Methylhistidine was 92% lower in vegans, and lower in lacto-ovo- and pesco-vegetarians by 90% and 80%, respectively, relative to non-vegetarians (P
Published:
2019
Title:
Post hoc analyses of surrogate markers of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in patients with type 2 diabetes in a digitally supported continuous care intervention: an open-label, non-randomised controlled study
Authors:
Vilar-Gomez, Eduardo; Athinarayanan, Shaminie J.; Adams, Rebecca N.; Hallberg, Sarah J.; Bhanpuri, Nasir H.; McKenzie, Amy L.; Campbell, Wayne W.; McCarter, James P.; Phinney, Stephen D.; Volek, Jeff S.; Chalasani, Naga
Abstract:
OBJECTIVE: One year of comprehensive continuous care intervention (CCI) through nutritional ketosis improves glycosylated haemoglobin(HbA1c), body weight and liver enzymes among patients with type 2 diabetes (T2D). Here, we report the effect of the CCI on surrogate scores of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. METHODS: This was a non-randomised longitudinal study, including adults with T2D who were self-enrolled to the CCI (n=262) or to receive usual care (UC, n=87) during 1 year. An NAFLD liver fat score (N-LFS) >-0.640 defined the presence of fatty liver. An NAFLD fibrosis score (NFS) of >0.675 identified subjects with advanced fibrosis. Changes in N-LFS and NFS at 1 year were the main endpoints. RESULTS: At baseline, NAFLD was present in 95% of patients in the CCI and 90% of patients in the UC. At 1 year, weight loss of ≥5% was achieved in 79% of patients in the CCI versus 19% of patients in UC (p<0.001). N-LFS mean score was reduced in the CCI group (-1.95±0.22, p<0.001), whereas it was not changed in the UC (0.47±0.41, p=0.26) (CCI vs UC, p<0.001). NFS was reduced in the CCI group (-0.65±0.06, p<0.001) compared with UC (0.26±0.11, p=0.02) (p<0.001 between two groups). In the CCI group, the percentage of individuals with a low probability of advanced fibrosis increased from 18% at baseline to 33% at 1 year (p
Published:
2019
Title:
Post-thawing metabolite profile and amino acid oxidation of thawed pork tenderloin by HVEF-A short communication
Authors:
Jia, G.; Sha, K.; Feng, X.; Liu, H.
Abstract:
The post-thawing quality, metabolite profile and amino acid oxidation of frozen pork tenderloin following the use of a high-voltage electrostatic field (HVEF) were investigated in this study. There were not significant differences of pH for pork thawed by air and HVEF, which were consistent with the lactic acid level and glycogen content. No changes in the tenderness of thawed pork were found. There were only 6 volatiles with different contents in the pork tenderloin (P 5 discriminating metabolites, among them, there were 10 discriminating metabolites in the glycerophospholipid metabolism (ssc00564) and retrograde endocannabinoid signaling (ssc04723). The glycerophospholipid metabolism could be related to the pork spoilage processes. © 2019 Elsevier Ltd
Published:
2019
Title:
Precocious myelination in a mouse model of autism
Authors:
Khanbabaei, Maryam; Hughes, Elizabeth; Ellegood, Jacob; Qiu, Lily R.; Yip, Raven; Dobry, Jenna; Murari, Kartikeya; Lerch, Jason P.; Rho, Jong M.; Cheng, Ning
Abstract:
Autism spectrum disorder (ASD) has been hypothesized to be a result of altered connectivity in the brain. Recent imaging studies suggest accelerated maturation of the white matter in young children with ASD, with underlying mechanisms unknown. Myelin is an integral part of the white matter and critical for connectivity; however, its role in ASD remains largely unclear. Here, we investigated myelin development in a model of idiopathic ASD, the BTBR mice. Magnetic resonance imaging revealed that fiber tracts in the frontal brain of the BTBR mice had increased volume at postnatal day 6, but the difference reduced over time, reminiscent of the findings in young patients. We further identified that myelination in the frontal brain of both male and female neonatal BTBR mice was increased, associated with elevated levels of myelin basic protein. However, myelin pattern was unaltered in adult BTBR mice, revealing accelerated developmental trajectory of myelination. Consistently, we found that signaling of platelet-derived growth factor receptor alpha (PDGFRα) was reduced in the frontal brain of neonatal BTBR mice. However, levels of microRNA species known to regulate PDGFRα signaling and myelination were unaltered. Together, these results suggest that precocious myelination could potentially contribute to increased volume and connectivity of the white matter observed in young children with ASD.
Published:
2019
Title:
Prevalence of Optimal Metabolic Health in American Adults: National Health and Nutrition Examination Survey 2009-2016
Authors:
Araújo, Joana; Cai, Jianwen; Stevens, June
Abstract:
Abstract Background: Several guidelines for cardiometabolic risk factor identification and management have been released in recent years, but there are no estimates of current prevalence of metabolic health among adults in the United States. We estimated the proportion of American adults with optimal cardiometabolic health, using different guidelines. Methods: Data from the National Health and Nutrition Examination Survey 2009–2016 were analyzed (n = 8721). Using the most recent guidelines, metabolic health was defined as having optimal levels of waist circumference (WC \textless102/88 cm for men/women), glucose (fasting glucose \textless100 mg/dL and hemoglobin A1c \textless5.7%), blood pressure (systolic \textless120 and diastolic \textless80 mmHg), triglycerides (\textless150 mg/dL), and high-density lipoprotein cholesterol (≥40/50 mg/dL for men/women), and not taking any related medication. Results: Changing from ATP III (Adult Treatment Panel III) guidelines to more recent cut points decreased the proportion of metabolically healthy Americans from...
Published:
2019
Title:
Prevention of atherothrombotic events in patients with diabetes mellitus: from antithrombotic therapies to new-generation glucose-lowering drugs
Authors:
Patti, Giuseppe; Cavallari, Ilaria; Andreotti, Felicita; Calabrò, Paolo; Cirillo, Plinio; Denas, Gentian; Galli, Mattia; Golia, Enrica; Maddaloni, Ernesto; Marcucci, Rossella; Parato, Vito Maurizio; Pengo, Vittorio; Prisco, Domenico; Ricottini, Elisabetta; Renda, Giulia; Santilli, Francesca; Simeone, Paola; De Caterina, Raffaele
Abstract:
Diabetes mellitus is an important risk factor for a first cardiovascular event and for worse outcomes after a cardiovascular event has occurred. This situation might be caused, at least in part, by the prothrombotic status observed in patients with diabetes. Therefore, contemporary antithrombotic strategies, including more potent agents or drug combinations, might provide greater clinical benefit in patients with diabetes than in those without diabetes. In this Consensus Statement, our Working Group explores the mechanisms of platelet and coagulation activity, the current debate on antiplatelet therapy in primary cardiovascular disease prevention, and the benefit of various antithrombotic approaches in secondary prevention of cardiovascular disease in patients with diabetes. While acknowledging that current data are often derived from underpowered, observational studies or subgroup analyses of larger trials, we propose antithrombotic strategies for patients with diabetes in various cardiovascular settings (primary prevention, stable coronary artery disease, acute coronary syndromes, ischaemic stroke and transient ischaemic attack, peripheral artery disease, atrial fibrillation, and venous thromboembolism). Finally, we summarize the improvements in cardiovascular outcomes observed with the latest glucose-lowering drugs, and on the basis of the available evidence, we expand and integrate current guideline recommendations on antithrombotic strategies in patients with diabetes for both primary and secondary prevention of cardiovascular disease.
Published:
2019
Title:
Receptors for advanced glycation end products is associated with autophagy in the clear cell renal cell carcinoma
Authors:
Guo, Yong; Zhang, Hai-Cong; Xue, Sheng; Zheng, Jun-Hua
Abstract:
Background: The receptor for advanced glycation end-product (RAGE) was one of the signal transduction receptors. RAGE interacted with various signaling molecules which were involved in human disease processes including tumorigenesis. Previous reports have indicated that RAGE/high-mobility group box 1 (HMGB1) could regulate autophagy in different carcinomas. However, the functional role of RAGE/ HMGB1 in the regulation of clear cell renal cell carcinoma (ccRCC) autophagy remained unrevealed. Methods: Western blot, quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence were used in the present study. Results: In this study, we demonstrated that the levels of RAGE/HMGB1 and autophagic protein LC3, Beclin-1, PI3K were much higher in ccRCC samples than those of in adjacent normal tissues. RAGE and autophagic protein expression was regulated with RAGE/HMGB1 in human RCC cell lines. Conclusion: Our results implicated that RAGE and autophagy played important roles in ccRCC, and RAGE/HMGB1 might serve as a novel therapeutic target for future ccRCC treatment.
Published:
2019
Title:
Reduction of Red and Processed Meat Intake and Cancer Mortality and Incidence A Systematic Review and Meta-analysis of Cohort Studies
Authors:
Han, Mi Ah; Zeraatkar, Dena; Guyatt, Gordon H; Vernooij, Robin W M; Dib, Regina El; Zhang, Ying; Algarni, Abdullah; Leung, Gareth; Storman, Dawid; Valli, Claudia; Lopes, Luciane Cruz; Sit, Daegan; Bala, Malgorzata M; Alonso-coello, Pablo
Abstract:
Published:
2019
Title:
Replacing meat with alternative plant-based products (RE-MAPs): Protocol for a randomised controlled trial of a behavioural intervention to reduce meat consumption
Authors:
Bianchi, F.; Aveyard, P.; Astbury, N.M.; Cook, B.; Cartwright, E.; Jebb, S.A.
Abstract:
Introduction Reducing meat consumption could contribute towards preventing some chronic conditions and protecting the natural environment. This study will examine the effectiveness of a behavioural intervention to reduce meat consumption. Methods and analyses Replacing meat with alternative plant-based product is a randomised controlled trial comparing a behavioural intervention to reduce meat consumption with a no intervention control condition. Eligible volunteers will be recruited from the general public through advertisement and randomised in a 1:1 ratio to receive no intervention or a 4-week intervention comprising the provision of free plant-based meat alternatives, written information on the health and environmental benefits of eating less meat, success stories of people who reduced their meat consumption and recipes. The primary outcome is the change in meat consumption at 4 weeks (T1) from baseline. Secondary and exploratory outcomes include changes in meat consumption at 8 weeks (T2) from baseline and changes from the baseline to both follow-up in other aspects of participants diet, putative psychosocial determinants of eating a low meat diet and of using meat substitutes and biomarkers of health risk, including blood lipid profiles, blood pressure, weight and body composition. Linear models will be employed to explore whether the changes in each of the aforementioned outcomes differ significantly between the control and intervention group. Qualitative interviews on a subsample of participants receiving the intervention will evaluate their experiences of the intervention and help to identify the mechanisms through which the intervention reduced meat consumption or the barriers preventing the intervention to aid this dietary transition. Ethics and dissemination The trial has been granted ethical approval by the Medical Sciences Interdivisional Research Ethics Committee (IDREC) of the University of Oxford (Ref: R54329/RE001). All results originating from this study will be submitted for publication in scientific journals and presented at meetings and through the media. Trial registration number ISRCTN13180635;Pre-recruitment. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.
Published:
2019
Title:
Response letter to 'does high LDL-cholesterol cause cardiovascular disease?'
Authors:
Ravnskov, Uffe; De Lorgeril, Michel; Diamond, David M.; Hama, Rokuro; Hamazaki, Tomohito; Hammarskjöld, Björn; Hynes, Niamh; Kendrick, Malcolm; Langsjoen, Peter H.; Mascitelli, Luca; McCully, Kilmer S.; Okuyama, Harumi; Rosch, Paul J.; Schersten, Tore; Sultan, Sherif; Sundberg, Ralf
Abstract:
Published:
2019
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