bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical Contrast and Raman Spectroscopy Techniques Applied to Few-Layer 2D Hexagonal Boron Nitride
Authors: Krečmarová Marie , Andres-Penares Daniel , Fekete Ladislav , Ashcheulov Petr , Molina-Sánchez Alejandro , Canet-Albiach Rodolfo , Gregora Ivan , Mortet Vincent , Martínez-Pastor Juan P. , Sánchez-Royo Juan F.
Published: July 2019

The successful integration of few-layer thick hexagonal boron nitride (hBN) into devices based on two-dimensional materials requires fast and non-destructive techniques to quantify their thickness. Optical contrast methods and Raman spectroscopy have been widely used to estimate the thickness of two-dimensional semiconductors and semi-metals. However, they have so far not been applied to two-dimensional insulators. In this work, we demonstrate the ability of optical contrast techniques to estimate the thickness of few-layer hBN on SiO2/Si substrates, which was also measured by atomic force microscopy. Optical contrast of hBN on SiO2/Si substrates exhibits a linear trend with the number of hBN monolayers in the few-layer thickness range. We also used bandpass filters (500–650 nm) to improve the effectiveness of the optical contrast methods for thickness estimations. We also investigated the thickness dependence of the high frequency in-plane E2g phonon mode of atomically thin hBN on SiO2/Si substrates by micro-Raman spectroscopy, which exhibits a weak thickness-dependence attributable to the in-plane vibration character of this mode. Ab initio calculations of the Raman active phonon modes of atomically thin free-standing crystals support these results, even if the substrate can reduce the frequency shift of the E2g phonon mode by reducing the hBN thickness. Therefore, the optical contrast method arises as the most suitable and fast technique to estimate the thickness of hBN nanosheets.
A Review on Brittle Fracture Nanomechanics by All-Atom Simulations
Authors: Patil Sandeep P. , Heider Yousef
Published: July 2019

Despite a wide range of current and potential applications, one primary concern of brittle materials is their sudden and swift collapse. This failure phenomenon exhibits an inability of the materials to sustain tension stresses in a predictable and reliable manner. However, advances in the field of fracture mechanics, especially at the nanoscale, have contributed to the understanding of the material response and failure nature to predict most of the potential dangers. In the following contribution, a comprehensive review is carried out on molecular dynamics (MD) simulations of brittle fracture, wherein the method provides new data and exciting insights into fracture mechanism that cannot be obtained easily from theories or experiments on other scales. In the present review, an abstract introduction to MD simulations, advantages, current limitations and their applications to a range of brittle fracture problems are presented. Additionally, a brief discussion highlights the theoretical background of the macroscopic techniques, such as Griffith’s criterion, crack tip opening displacement, J-integral and other criteria that can be linked to the fracture mechanical properties at the nanoscale. The main focus of the review is on the recent advances in fracture analysis of highly brittle materials, such as carbon nanotubes, graphene, silicon carbide, amorphous silica, calcium carbonate and silica aerogel at the nanoscale. These materials are presented here due to their extraordinary mechanical properties and a wide scope of applications. The underlying review grants a more extensive unravelling of the fracture behaviour and mechanical properties at the nanoscale of brittle materials.
Quality of Life in Chronic Ketogenic Diet Treatment: The GLUT1DS Population Perspective
Authors: Varesio Costanza , Pasca Ludovica , Parravicini Stefano , Zanaboni Martina Paola , Ballante Elena , Masnada Silvia , Ferraris Cinzia , Bertoli Simona , Tagliabue Anna , Veggiotti Pierangelo , De Giorgis Valentina
Published: July 2019

Background: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare, genetically determined neurological disorder, for which Ketogenic Diet (KD) represents the gold standard life-long treatment. The aim of this study is to investigate health related quality of life in a well characterized cohort of patients affected by GLUT1DS treated with KD, evaluating factors that can influence patients’ and parents’ quality of life perception. Methods: This is a double center exploratory research study. A postal survey with auto-administrable questionnaires was conducted among 17 subjects (aged 3–22 years) with diagnosis of GLUT1DS, receiving a stable KD treatment for more than 1 year. The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales was adopted. Clinical variables analyzed in relation to quality of life were frequency of epileptic seizures and movement disorder since KD introduction, presence of intellectual disability (ID), and KD ratio. Results: Quality of life global scores were impaired both in parents’ and children’s perspectives, with a significant concordance. Taking into consideration subscales, the average was 64.17 (range 10–100) for physical functioning, 74.23 (range 30–100) for emotional functioning, 62.64 (range 10–100) for social functioning, and 56 (range 15–92) for school functioning. Conclusions: In patients with GLUT1DS the quality of life perception is comparable to that of other patients with chronic disease. In our sample, the presence of movement disorder seems to be a crucial element in quality of life perception.
Plasma Phospholipid Fatty Acids and Risk of Atrial Fibrillation: A Mendelian Randomization Study
Authors: Yuan Shuai , Larsson Susanna C.
Published: July 2019

Available evidence on the associations of dietary and circulating levels of long-chain n-3 fatty acids, which have potential antiarrhythmic properties, and other fatty acids with atrial fibrillation is conflicting and limited. We conducted a Mendelian randomization study to assess the associations between plasma phospholipid fatty acid levels and atrial fibrillation. Summary-level data of atrial fibrillation were available from 65,446 cases and 522,744 non-cases included in the Atrial Fibrillation Consortium. Sixteen single-nucleotide polymorphisms associated with ten fatty acids at significance level of p < 5 × 10−8 were identified as instrumental variables from the hitherto largest genome-wide association studies for plasma fatty acids. The fixed-effects inverse-variance weighted method was used to assess the association of individual plasma fatty acids and atrial fibrillation risk. The random-effects inverse-variance weighted method, weighted median method, and Mendelian randomization (MR)-Egger method were employed as the sensitivity analyses. Genetic predisposition to higher levels of any of the ten individual fatty acids was not associated with atrial fibrillation risk.
Effect of Vasicinone against Paraquat-Induced MAPK/p53-Mediated Apoptosis via the IGF-1R/PI3K/AKT Pathway in a Parkinson’s Disease-Associated SH-SY5Y Cell Model
Authors: Ju Da-Tong , Sivalingam Kalaiselvi , Kuo Wei-Wen , Ho Tsung-Jung , Chang Ruey-Lin , Chung Li-Chin , Day Cecilia Hsuan , Viswanadha Vijaya Padma , Liao Po-Hsiang , Huang Chih-Yang
Published: July 2019

Vasicinone is a quinazoline alkaloid isolated from the Adhatoda vasica plant. In this study, we explored the neuroprotective effect and underlying molecular mechanism of vasicinone against paraquat-induced cellular apoptosis in SH-SY5Y cells. Vasicinone reduced the paraquat-induced loss of cell viability, rescued terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL)-positive apoptotic nuclei, and suppressed generation of reactive oxygen species (ROS) in a dose-dependent manner. Western blotting analysis revealed that vasicinone increased the phosphorylation of IGF1R/PI3K/AKT cell survival signaling molecules and downregulated the paraquat-induced, mitogen-activated protein kinase (MAPK)/c-Jun N-terminal kinase (JNK)-mediated apoptotic pathways compared to that observed in cells not treated with vasicinone. This protection depended critically on the activation of IGF1R, and the silencing of IGF1R by siRNA completely abrogated the protective effect of vasicinone in SH-SY5Y cells. Our findings indicated that vasicinone is a potential candidate for the treatment of Parkinson’s disease and possibly other oxidative stress-related neurodegenerative disorders.
Extra Virgin Olive Oil Contains a Phenolic Inhibitor of the Histone Demethylase LSD1/KDM1A
Authors: Cuyàs Elisabet , Gumuzio Juan , Lozano-Sánchez Jesús , Carreras David , Verdura Sara , Llorach-Parés Laura , Sanchez-Martinez Melchor , Selga Elisabet , Pérez Guillermo J. , Scornik Fabiana S. , Brugada Ramon , Bosch-Barrera Joaquim , Segura-Carretero Antonio , Martin Ángel G. , Encinar José Antonio , Menendez Javier A.
Published: July 2019

The lysine-specific histone demethylase 1A (LSD1) also known as lysine (K)-specific demethylase 1A (KDM1A) is a central epigenetic regulator of metabolic reprogramming in obesity-associated diseases, neurological disorders, and cancer. Here, we evaluated the ability of oleacein, a biophenol secoiridoid naturally present in extra virgin olive oil (EVOO), to target LSD1. Molecular docking and dynamic simulation approaches revealed that oleacein could target the binding site of the LSD1 cofactor flavin adenosine dinucleotide with high affinity and at low concentrations. At higher concentrations, oleacein was predicted to target the interaction of LSD1 with histone H3 and the LSD1 co-repressor (RCOR1/CoREST), likely disturbing the anchorage of LSD1 to chromatin. AlphaScreen-based in vitro assays confirmed the ability of oleacein to act as a direct inhibitor of recombinant LSD1, with an IC50 as low as 2.5 μmol/L. Further, oleacein fully suppressed the expression of the transcription factor SOX2 (SEX determining Region Y-box 2) in cancer stem-like and induced pluripotent stem (iPS) cells, which specifically occurs under the control of an LSD1-targeted distal enhancer. Conversely, oleacein failed to modify ectopic SOX2 overexpression driven by a constitutive promoter. Overall, our findings provide the first evidence that EVOO contains a naturally occurring phenolic inhibitor of LSD1, and support the use of oleacein as a template to design new secoiridoid-based LSD1 inhibitors.
Differential Stimulation of Post-Exercise Myofibrillar Protein Synthesis in Humans Following Isonitrogenous, Isocaloric Pre-Exercise Feeding
Authors: Davies Robert W. , Bass Joseph J. , Carson Brian P. , Norton Catherine , Kozior Marta , Amigo-Benavent Miryam , Wilkinson Daniel J. , Brook Matthew S. , Atherton Philip J. , Smith Kenneth , Jakeman Philip M.
Published: July 2019

The aim of this study was to test the effects of two disparate isonitrogenous, isocaloric pre-exercise feeds on deuterium-oxide (D2O) derived measures of myofibrillar protein synthesis (myoPS) in humans. Methods: In a double-blind parallel group design, 22 resistance-trained men aged 18 to 35 years ingested a meal (6 kcal·kg−1, 0.8 g·kg−1 carbohydrate, 0.2 g·kg−1 fat) with 0.33 g·kg−1 nonessential amino acids blend (NEAA) or whey protein (WHEY), prior to resistance exercise (70% 1RM back-squats, 10 reps per set to failure, 25% duty cycle). Biopsies of M. vastus lateralis were obtained pre-ingestion (PRE) and +3 h post-exercise (POST). The myofibrillar fractional synthetic rate (myoFSR) was calculated via deuterium labelling of myofibrillar-bound alanine, measured by gas chromatography–pyrolysis–isotope ratio mass spectrometry (GC-Pyr-IRMS). Data are a mean percentage change (95% CI). Results: There was no discernable change in myoFSR following NEAA (10(−5, 25) %, p = 0.235), whereas an increase in myoFSR was observed after WHEY (28 (13, 43) %, p = 0.003). Conclusions: Measured by a D2O tracer technique, a disparate myoPS response was observed between NEAA and WHEY. Pre-exercise ingestion of whey protein increased post-exercise myoPS, whereas a NEAA blend did not, supporting the use of NEAA as a viable isonitrogenous negative control.
Associations of Weekday and Weekend Sleep with Children’s Reported Eating in the Absence of Hunger
Authors: LeMay-Russell Sarah , Tanofsky-Kraff Marian , Schvey Natasha A. , Kelly Nichole R. , Shank Lisa M. , Mi Sarah J. , Jaramillo Manuela , Ramirez Sophie , Altman Deborah R. , Rubin Sarah G. , Byrne Meghan E. , Burke Natasha L. , Davis Elisabeth K. , Broadney Miranda M. , Brady Sheila M. , Yanovski Susan Z. , Yanovski Jack A.
Published: July 2019

Insufficient average sleep duration has been inconsistently associated with poor diet and obesity risks in youth. Inconsistencies in findings across studies may be due to a general failure to examine associations in weekday versus weekend sleep. We hypothesized that greater variations in weekday and weekend sleep duration would be associated with more disinhibited eating behaviors, which, in turn, might be involved in the relationship between sleep and weight. We, therefore, examined, among healthy, non-treatment seeking youth, the associations of average weekly, weekend, and weekday sleep duration with eating in the absence of hunger (EAH), a disinhibited eating behavior associated with disordered eating and obesity. Sleep was assessed via actigraphy for 14 days. Participants completed a self-report measure of EAH. Adiposity was measured by dual-energy X-ray absorptiometry. Linear regressions were used to test the associations of sleep duration with EAH and the associations of sleep duration and EAH, with fat mass. Among 123 participants (8–17 years, 52.0% female, and 30.9% with overweight), there was no significant association between average weekly sleep and EAH. Further, there was no significant association among average weekly sleep duration or EAH and fat mass. However, average weekday sleep was negatively associated, and average weekend sleep was positively associated, with EAH (ps < 0.02). Weekend “catch-up” sleep (the difference between weekend and weekday sleep) was positively associated with EAH (p < 0.01). Findings indicate that shorter weekday sleep and greater weekend “catch-up” sleep are associated with EAH, which may place youth at risk for the development of excess weight gain over time.
Biological Effect of Soy Isoflavones in the Prevention of Civilization Diseases
Authors: Pabich Marzena , Materska Małgorzata
Published: July 2019

Scientific advancements in recent years have shed new light on the relationship between diet and human health. Nutrients play an important role in the prevention of many civilization diseases, such as osteoporosis, type II diabetes, hypercholesterolemia, and cardiovascular diseases. The biological activity of natural plant components allows their use in the treatment of various diseases, especially civilization diseases, to be speculated. Special attention is paid to phenolic compounds that have numerous health-promoting properties. Isoflavones, phenolic compounds, are commonly found in legumes, especially in soybeans. Their structural similarity to 17-β-estradiol (E2), the main female sex hormone, allows them to induce estrogenic and antiestrogenic effects by binding to estrogen receptors, and their consumption has been associated with a decreased risk of hormone-related cancers. In addition, numerous epidemiological studies and related meta-analyses suggest that soy consumption may be associated with a lower incidence of certain diseases. However, there are some doubts about the potential effects on health, such as the effectiveness of cardiovascular risk reduction or breast cancer-promoting properties. The purpose of this review is to present the current knowledge on the potential effects of soy isoflavone consumption with regard to civilization diseases.
Acute Caffeine and Coconut Oil Intake, Isolated or Combined, Does Not Improve Running Times of Recreational Runners: A Randomized, Placebo-Controlled and Crossover Study
Authors: Borba Gabrielle de Lima , Batista Julianne Soares de Freitas , Novais Ludmilla Marques Queiroz , Silva Myrnzzia Beatriz , Silva Júnior João Batista da , Gentil Paulo , Marini Ana Clara Baretto , Giglio Bruna Melo , Pimentel Gustavo Duarte
Published: July 2019

The aim was to evaluate the effect of caffeine (CAF) and extra virgin coconut oil (CO), isolated or combined, on running performance in runners. Methods: A randomized, placebo-controlled, and crossover study was conducted with thirteen recreational runners aged 18–40. All volunteers performed a 1600 m time trial at a 400 m track, each ingesting four different substances: (1) placebo (water), (2) decaffeinated coffee plus isolated CAF (DECAF + CAF), (3) decaffeinated coffee plus isolated CAF plus soy oil (DECAF + CAF + SO), and (4) decaffeinated coffee plus isolated CAF plus extra virgin coconut oil (DECAF + CAF + CO). The substances were ingested 60 min before the trials, the order of the situations was randomized, and there were one-week intervals between them. At the end of the trials, the Borg scale was applied to evaluate the rating of perceived exertion (RPE) and the time was measured. Results: Our data did not show differences in running time among the trials (placebo: 7.64 ± 0.80, DECAF + CAF: 7.61 ± 1.02, DECAF + CAF + SO: 7.66 ± 0.89, and DECAF + CAF + CO: 7.58 ± 0.74 min; p = 0.93), nor RPE (placebo: 6.15 ± 2.03, DECAF + CAF: 6.00 ± 2.27, DECAF + CAF + SO: 6.54 ± 2.73, and DECAF + CAF + CO: 6.00 ± 2.45 score; p = 0.99). Lactate concentrations (placebo: 6.23 ± 2.72, DECAF + CAF: 4.43 ± 3.77, DECAF + CAF + SO: 5.29 ± 3.77, and DECAF + CAF + CO: 6.17 ± 4.18 mmol/L; p = 0.55) also was not modified. Conclusion: Our study shows that ingestion of decaffeinated coffee with the addition of isolated CAF and extra virgin CO, either isolated or combined, does not improve 1600 m running times, nor influence RPE and lactate concentrations in recreational runners. Thus, combination of coffee with CO as a pre-workout supplement seems to be unsubstantiated for a short-distance race.
A Dietary Intervention with Reduction of Starch and Sucrose Leads to Reduced Gastrointestinal and Extra-Intestinal Symptoms in IBS Patients
Authors: Nilholm Clara , Roth Bodil , Ohlsson Bodil
Published: July 2019

Patients with irritable bowel syndrome (IBS) exhibit low-grade inflammation and increased gut permeability. Dietary sugar has been shown to contribute to low-grade inflammation and increased gut permeability, and to correlate with gastrointestinal (GI) symptoms. The aim of the present study was to examine the effect of a starch- and sucrose-reduced diet (SSRD) on gastrointestinal (GI) and extra-intestinal symptoms in IBS. One hundred and five IBS patients (82 women, 46.06 ± 13.11 years), with irritable bowel syndrome-symptom severity scale (IBS-SSS) > 175, were randomized to SSRD for 4 weeks or continued ordinary eating habits. The visual analog scale for irritable bowel syndrome (VAS-IBS), IBS-SSS, and 4-day food diaries were collected at baseline and after 2 and 4 weeks. After the intervention, one-third of the patients did not fulfill the criteria for IBS/functional gastrointestinal disorder. Half of the participants changed from moderate/severe disease to no/mild disease according to IBS-SSS. Comparisons between the groups showed decreased weight and sweet cravings, and parallel decreases in total IBS-SSS and extra-intestinal IBS-SSS scores, in the intervention group compared to controls (p < 0.001 for all). When calculating separate extra-intestinal symptoms, belching (p = 0.001), muscle/joint pain (p = 0.029), urinary urgency (p = 0.017), and tiredness (p = 0.011) were decreased after introduction of SSRD compared to controls. In conclusion, SSRD improves both GI and extra-intestinal symptoms in IBS.
Lipotoxicity in Kidney, Heart, and Skeletal Muscle Dysfunction
Authors: Nishi Hiroshi , Higashihara Takaaki , Inagi Reiko
Published: July 2019

Dyslipidemia is a common nutritional and metabolic disorder in patients with chronic kidney disease. Accumulating evidence supports the hypothesis that prolonged metabolic imbalance of lipids leads to ectopic fat distribution in the peripheral organs (lipotoxicity), including the kidney, heart, and skeletal muscle, which accelerates peripheral inflammation and afflictions. Thus, lipotoxicity may partly explain progression of renal dysfunction and even extrarenal complications, including renal anemia, heart failure, and sarcopenia. Additionally, endoplasmic reticulum stress activated by the unfolded protein response pathway plays a pivotal role in lipotoxicity by modulating the expression of key enzymes in lipid synthesis and oxidation. Here, we review the molecular mechanisms underlying lipid deposition and resultant tissue damage in the kidney, heart, and skeletal muscle, with the goal of illuminating the nutritional aspects of these pathologies.
Association of Diet Quality and Vegetable Variety with the Risk of Cognitive Decline in Chinese Older Adults
Authors: Chou Yi-Chun , Lee Meei-Shyuan , Chiou Jeng-Min , Chen Ta-Fu , Chen Yen-Ching , Chen Jen-Hau
Published: July 2019

Diet quality plays an important role in dementia prevention. It remains unclear how the joint effect of vegetable variety and diet quality affects cognition. This study aimed to explore the association of diet quality and vegetable variety with cognitive decline in older adults. This prospective cohort study (2011–2015) included 436 community-dwelling elders in Taipei. Diet quality, assessed by the modified Alternative Healthy Eating Index (mAHEI), was computed from a food frequency questionnaire at baseline (2011–2013). Vegetable variety indicated the number of different vegetable groups, adjusted for vegetable quantity. Multivariable linear and logistic regression models were used to explore the association of diet quality and vegetable variety with the decline of global and domain-specific cognition over two years. Our findings suggest that high diet quality (the highest tertile of mAHEI) was associated with a lower risk of both global cognitive decline (adjusted odds ratio (AOR) = 0.54, confidence interval (CI) = 0.31–0.95) and decline of attention domain (AOR = 0.56, CI = 0.32–0.99) compared with low diet quality. In elders with high vegetable variety, high diet quality was associated with a lower risk of global cognitive decline (AOR = 0.49, CI = 0.26–0.95). We therefore concluded that high diet quality along with diverse vegetable intake was associated with a lower risk of cognitive decline in older adults.
Can Nutritional Intervention for Obesity and Comorbidities Slow Down Age-Related Hearing Impairment?
Authors: Tang Ting-Hsuan , Hwang Juen-Haur , Yang Ting-Hua , Hsu Chuan-Jen , Wu Chen-Chi , Liu Tien-Chen
Published: July 2019

Background: Age-related hearing impairment (ARHI), the most common sensory deficit in the elderly, is associated with enormous social and public health burdens. Emerging evidence has suggested that obesity and comorbidities might increase the risk of ARHI. However, no reviews have been published that address the role of nutritional interventions for obesity and comorbidities in the prevention of ARHI. Methods: A PubMed database search was conducted to identify the relationship between obesity and ARHI. “Obesity”, “metabolic syndrome”, “adipose-derived hormone”, “fatty acid”, and “age-related hearing impairment” were included as keywords. Results: A total of 89 articles was analyzed with 39 articles of relevance to ARHI. A high-fat diet may induce oxidative stress, mitochondrial damage, and apoptosis in the inner ear. Statins have been shown to delay the progression of ARHI by improving the lipid profile, reducing oxidative stress, and inhibiting endothelial inflammation. Aldosterone could exert protective effects against ARHI by upregulating the Na-K-2Cl co-transporter 1 in the cochlea. Omega-3 polyunsaturated fatty acids could preserve the cochlear microcirculation by reducing dyslipidemia and inhibiting inflammation. Alpha-lipoic acid and lecithin might delay the progression of ARHI by protecting cochlear mitochondrial DNA from damage due to oxidative stress. Tea and ginseng might protect against ARHI through their anti-obesity and anti-diabetic effects. Conclusions: Nutritional interventions for obesity and comorbidities, including a low-fat diet, supplementation with statins, aldosterone, omega-3 polyunsaturated fatty acids, alpha-lipoic acids, lecithin, tea, and ginseng, may protect against the development of ARHI.
A Mitochondrial Specific Antioxidant Reverses Metabolic Dysfunction and Fatty Liver Induced by Maternal Cigarette Smoke in Mice
Authors: Li Gerard , Chan Yik , Sukjamnong Suporn , Anwer Ayad , Vindin Howard , Padula Matthew , Zakarya Razia , George Jacob , Oliver Brian , Saad Sonia , Chen Hui
Published: July 2019

Maternal smoking leads to glucose and lipid metabolic disorders and hepatic damage in the offspring, potentially due to mitochondrial oxidative stress. Mitoquinone mesylate (MitoQ) is a mitochondrial targeted antioxidant with high bioavailability. This study aimed to examine the impact of maternal cigarette smoke exposure (SE) on offspring’s metabolic profile and hepatic damage, and whether maternal MitoQ supplementation during gestation can affect these changes. Female Balb/c mice (eight weeks) were either exposed to air or SE for six weeks prior to mating and throughout gestation and lactation. A subset of the SE dams were supplied with MitoQ in the drinking water (500 µmol/L) during gestation and lactation. Intraperitoneal glucose tolerance test was performed in the male offspring at 12 weeks and the livers and plasma were collected at 13 weeks. Maternal SE induced glucose intolerance, hepatic steatosis, mitochondrial oxidative stress and related damage in the adult offspring. Maternal MitoQ supplementation reduced hepatic mitochondrial oxidative stress and improved markers of mitophagy and mitochondrial biogenesis. This may restore hepatic mitochondrial health and was associated with an amelioration of glucose intolerance, hepatic steatosis and pathological changes induced by maternal SE. MitoQ supplementation may potentially prevent metabolic dysfunction and hepatic pathology induced by intrauterine SE.
Plasma Phospholipid Fatty Acids and Coronary Heart Disease Risk: A Matched Case-Control Study within the Women’s Health Initiative Observational Study
Authors: Liu Qing , Matthan Nirupa R. , Manson JoAnn E. , Howard Barbara V. , Tinker Lesley F. , Neuhouser Marian L. , Van Horn Linda V. , Rossouw Jacques E. , Allison Matthew A. , Martin Lisa W. , Li Wenjun , Snetselaar Linda G. , Wang Lu , Lichtenstein Alice H. , Eaton Charles B.
Published: July 2019

Background and Aims: The association of fatty acids with coronary heart disease (CHD) has been examined, mainly through dietary measurements, and has generated inconsistent results due to measurement error. Large observational studies and randomized controlled trials have shown that plasma phospholipid fatty acids (PL-FA), especially those less likely to be endogenously synthesized, are good biomarkers of dietary fatty acids. Thus, PL-FA profiles may better predict CHD risk with less measurement error. Methods: We performed a matched case-control study of 2428 postmenopausal women nested in the Women’s Health Initiative Observational Study. Plasma PL-FA were measured using gas chromatography and expressed as molar percentage (moL %). Multivariable conditional logistic regression was used to calculate odds ratios (95% CIs) for CHD associated with 1 moL % change in PL-FA. Results: Higher plasma PL long-chain saturated fatty acids (SFA) were associated with increased CHD risk, while higher n-3 polyunsaturated fatty acids (PUFA) were associated with decreased risk. No significant associations were observed for very-long-chain SFA, monounsaturated fatty acids (MUFA), PUFA n-6 or trans fatty acids (TFA). Substituting 1 moL % PUFA n-6 or TFA with an equivalent proportion of PUFA n-3 were associated with lower CHD risk. Conclusions: Higher plasma PL long-chain SFA and lower PUFA n-3 were associated with increased CHD risk. A change in diet by limiting foods that are associated with plasma PL long-chain SFA and TFA while enhancing foods high in PUFA n-3 may be beneficial in CHD among postmenopausal women.
Effects of Paramylon Extracted from Euglena gracilis EOD-1 on Parameters Related to Metabolic Syndrome in Diet-Induced Obese Mice
Authors: Aoe Seiichiro , Yamanaka Chiemi , Koketsu Kotone , Nishioka Machiko , Onaka Nobuteru , Nishida Norihisa , Takahashi Madoka
Published: July 2019

Paramylon (PM), a type of β-glucan, functions like dietary fiber, which has been suggested to exert a protective effect against obesity. We evaluated the potential beneficial effects of PM powder on obesity in mice. Male C57BL/6J mice were fed a high-fat diet supplemented with either 2.5 or 5% PM powder, extracted from Euglena gracilis, for 74 days. Growth parameters, abdominal fat content, serum biochemical markers, hepatic lipid accumulation and hepatic mRNA expression were measured. Dietary supplementation with PM resulted in decreased food efficiency ratios and abdominal fat accumulation. Dose-dependent decreases were observed in postprandial glucose levels, serum low-density lipoprotein (LDL)-cholesterol, and serum secretary immunoglobulin A (sIgA) concentrations. PM supplementation increased peroxisome proliferator-activated receptor α (PPARα) mRNA expression in the liver which is suggested to induce β-oxidation through activation of acyl-coenzyme A oxidase (ACOX), carnitine palmitoyltransferase (CPT) and fatty acid transport protein 2 (FATP2) mRNA expression. Changes in fatty acid metabolism may improve lipid and glucose metabolism. In conclusion, a preventive effect against obesity was observed in mice given a PM-enriched diet. The mechanism is suggested to involve a reduction in both serum LDL-cholesterol levels and the accumulation of abdominal fat, in addition to an improvement in postprandial glucose concentration.
Vitamin D and Phenylbutyrate Supplementation Does Not Modulate Gut Derived Immune Activation in HIV-1
Authors: Missailidis Catharina , Sørensen Nikolaj , Ashenafi Senait , Amogne Wondwossen , Kassa Endale , Bekele Amsalu , Getachew Meron , Gebreselassie Nebiat , Aseffa Abraham , Aderaye Getachew , Andersson Jan , Brighenti Susanna , Bergman Peter
Published: July 2019

Dysbiosis and a dysregulated gut immune barrier function contributes to chronic immune activation in HIV-1 infection. We investigated if nutritional supplementation with vitamin D and phenylbutyrate could improve gut-derived inflammation, selected microbial metabolites, and composition of the gut microbiota. Treatment-naïve HIV-1-infected individuals (n = 167) were included from a double-blind, randomized, and placebo-controlled trial of daily 5000 IU vitamin D and 500 mg phenylbutyrate for 16 weeks (Clinicaltrials.gov NCT01702974). Baseline and per-protocol plasma samples at week 16 were analysed for soluble CD14, the antimicrobial peptide LL-37, kynurenine/tryptophan-ratio, TMAO, choline, and betaine. Assessment of the gut microbiota involved 16S rRNA gene sequencing of colonic biopsies. Vitamin D + phenylbutyrate treatment significantly increased 25-hydroxyvitamin D levels (p < 0.001) but had no effects on sCD14, the kynurenine/tryptophan-ratio, TMAO, or choline levels. Subgroup-analyses of vitamin D insufficient subjects demonstrated a significant increase of LL-37 in the treatment group (p = 0.02), whereas treatment failed to significantly impact LL-37-levels in multiple regression analysis. Further, no effects on the microbiota was found in number of operational taxonomic units (p = 0.71), Shannon microbial diversity index (p = 0.82), or in principal component analyses (p = 0.83). Nutritional supplementation with vitamin D + phenylbutyrate did not modulate gut-derived inflammatory markers or microbial composition in treatment-naïve HIV-1 individuals with active viral replication.
Linseed Components Are More Effective Than Whole Linseed in Reversing Diet-Induced Metabolic Syndrome in Rats
Authors: Shafie Siti Raihanah , Wanyonyi Stephen , Panchal Sunil K. , Brown Lindsay
Published: July 2019

Linseed is a dietary source of plant-based ω–3 fatty acids along with fiber as well as lignans including secoisolariciresinol diglucoside (SDG). We investigated the reversal of signs of metabolic syndrome following addition of whole linseed (5%), defatted linseed (3%), or SDG (0.03%) to either a high-carbohydrate, high-fat or corn starch diet for rats for the final eight weeks of a 16–week protocol. All interventions reduced plasma insulin, systolic blood pressure, inflammatory cell infiltration in heart, ventricular collagen deposition, and diastolic stiffness but had no effect on plasma total cholesterol, nonesterified fatty acids, or triglycerides. Whole linseed did not change the body weight or abdominal fat in obese rats while SDG and defatted linseed decreased abdominal fat and defatted linseed increased lean mass. Defatted linseed and SDG, but not whole linseed, improved heart and liver structure, decreased fat vacuoles in liver, and decreased plasma leptin concentrations. These results show that the individual components of linseed produce greater potential therapeutic responses in rats with metabolic syndrome than whole linseed. We suggest that the reduced responses indicate reduced oral bioavailability of the whole seeds compared to the components.
Daily Intake of Fermented Milk Containing Lactobacillus casei Shirota (Lcs) Modulates Systemic and Upper Airways Immune/Inflammatory Responses in Marathon Runners
Authors: Vaisberg Mauro , Paixão Vitoria , Almeida Ewin , Santos Juliana , Foster Roberta , Rossi Marcelo , Pithon-Curi Tania , Gorjão Renata , Momesso Cesar , Andrade Marília , Araujo José , Garcia Maurício , Cohen Moises , Perez Elizabeth , Santos-Dias Alana , Vieira Rodolfo , Bachi André
Published: July 2019

Background. Although Lactobacillus casei Shirota (LcS) can benefit the immune status, the effects of LcS in the immune/inflammatory responses of marathon runners has never been evaluated. Therefore, here we evaluated the effect of daily ingestion of fermented milk containing or not LcS in the systemic and upper airway immune/inflammatory responses before and after a marathon. Methods. Forty-two male marathon runners ingested a fermented milk containing 40 billion of LcS/day (LcS group, n = 20) or placebo (unfermented milk, n = 22) during 30 days pre-marathon. Immune/inflammatory parameters in nasal mucosa and serum, as well as concentrations of secretory IgA (SIgA) and antimicrobial peptides in saliva, were evaluated before and after fermented milk ingestion, immediately, 72 h, and 14 d post-marathon. Results. Higher proinflammatory cytokine levels in serum and nasal mucosa, and also lower salivary levels of SIgA and antimicrobial peptides, were found immediately post-marathon in the placebo group compared to other time points and to LcS group. In opposite, higher anti-inflammatory levels and reduced neutrophil infiltration on nasal mucosa were found in the LcS group compared to other time points and to the placebo group. Conclusion. For the first time, it is shown that LcS is able to modulate the systemic and airways immune responses post-marathon.
The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure
Authors: Khalaf David , Krüger Marcus , Wehland Markus , Infanger Manfred , Grimm Daniela
Published: July 2019

Nitric oxide (NO) is a well-known vasodilator produced by the vascular endothelium via the enzyme endothelial nitric oxide synthase (eNOS). The inadequate production of NO has been linked to elevated blood pressure (BP) in both human and animal studies, and might be due to substrate inaccessibility. This review aimed to investigate whether oral administration of the amino acids l-arginine (Arg) and l-citrulline (Cit), which are potential substrates for eNOS, could effectively reduce BP by increasing NO production. Both Arg and Cit are effective at increasing plasma Arg. Cit is approximately twice as potent, which is most likely due to a lower first-pass metabolism. The current data suggest that oral Arg supplementation can lower BP by 5.39/2.66 mmHg, which is an effect that is comparable with diet changes and exercise implementation. The antihypertensive properties of Cit are more questionable, but are likely in the range of 4.1/2.08 to 7.54/3.77 mmHg. The exact mechanism by which Cit and Arg exert their effect is not fully understood, as normal plasma Arg concentration greatly exceeds the Michaelis constant (Km) of eNOS. Thus, elevated plasma Arg concentrations would not be expected to increase endogenous NO production significantly, but have nonetheless been observed in other studies. This phenomenon is known as the “l-arginine paradox”.
Food and Nutrient Intake during Pregnancy in Relation to Maternal Characteristics: Results from the NICE Birth Cohort in Northern Sweden
Authors: Stråvik Mia , Jonsson Karin , Hartvigsson Olle , Sandin Anna , Wold Agnes E. , Sandberg Ann-Sofie , Barman Malin
Published: July 2019

Linkages between diet and other lifestyle factors may confound observational studies. We used cluster analysis to analyze how the intake of food and nutrients during pregnancy co-varies with lifestyle, clinical and demographic factors in 567 women who participated in the NICE (nutritional impact on immunological maturation during childhood in relation to the environment) birth-cohort in northern Sweden. A food frequency questionnaire, Meal-Q, was administered in pregnancy Week 34, and the reported food and nutrient intakes were related to maternal characteristics such as age, education, rural/town residence, parity, pre-pregnancy smoking, first-trimester BMI, allergy and hyperemesis. Two lifestyle-diet clusters were identified: (1) High level of education and higher age were related to one another, and associated with a diet rich in fruits, vegetables, whole grains and fish, and (2) smoking before pregnancy and higher BMI in early pregnancy were related to one another and associated with a diet that contained white bread, French fries, pizza, meat, soft drinks, candy and snacks. More than half of the women had lower-than-recommended daily intake levels of vitamin D, folate, selenium, and iodine. Complex lifestyle-diet interactions should be considered in observational studies that link diet and pregnancy outcome.
Phenotyping Women Based on Dietary Macronutrients, Physical Activity, and Body Weight Using Machine Learning Tools
Authors: Ramyaa Ramyaa , Hosseini Omid , Krishnan Giri P. , Krishnan Sridevi
Published: July 2019

Nutritional phenotyping can help achieve personalized nutrition, and machine learning tools may offer novel means to achieve phenotyping. The primary aim of this study was to use energy balance components, namely input (dietary energy intake and macronutrient composition) and output (physical activity) to predict energy stores (body weight) as a way to evaluate their ability to identify potential phenotypes based on these parameters. From the Women’s Health Initiative Observational Study (WHI OS), carbohydrates, proteins, fats, fibers, sugars, and physical activity variables, namely energy expended from mild, moderate, and vigorous intensity activity, were used to predict current body weight (both as body weight in kilograms and as a body mass index (BMI) category). Several machine learning tools were used for this prediction. Finally, cluster analysis was used to identify putative phenotypes. For the numerical predictions, the support vector machine (SVM), neural network, and k-nearest neighbor (kNN) algorithms performed modestly, with mean approximate errors (MAEs) of 6.70 kg, 6.98 kg, and 6.90 kg, respectively. For categorical prediction, SVM performed the best (54.5% accuracy), followed closely by the bagged tree ensemble and kNN algorithms. K-means cluster analysis improved prediction using numerical data, identified 10 clusters suggestive of phenotypes, with a minimum MAE of ~1.1 kg. A classifier was used to phenotype subjects into the identified clusters, with MAEs <5 kg for 15% of the test set (n = ~2000). This study highlights the challenges, limitations, and successes in using machine learning tools on self-reported data to identify determinants of energy balance.
The Influence of Red Meat on Colorectal Cancer Occurrence Is Dependent on the Genetic Polymorphisms of S-Glutathione Transferase Genes
Authors: Klusek Justyna , Nasierowska-Guttmejer Anna , Kowalik Artur , Wawrzycka Iwona , Chrapek Magdalena , Lewitowicz Piotr , Radowicz-Chil Agnieszka , Klusek Jolanta , Głuszek Stanisław
Published: July 2019

Background: It is postulated that both individual genotype and environmental factors such as diet may modify the risk of developing colorectal cancer (CRC). The influences of GST gene polymorphism and red meat intake on CRC occurrence in the Polish population were analyzed in this study. Methods: Genotyping was performed with the qPCR method. Results: A high frequency of meat consumption was associated with an over 2-fold increase in the risk of colorectal cancer odds ratio (OR) adjusted for sex and age = 2.4, 95% confidence interval (CI); 1.3–4.4). However, after analyzing the genetic profiles, in the absence of polymorphisms of all three analyzed genes, there was no association between a high frequency of meat consumption and the occurrence of CRC. In the case of GSTM1 gene polymorphism, the high frequency of meat consumption increased the risk of CRC by almost more than 4 times (OR adjusted for sex and age = 3.8, 95% CI: 1.6–9.1). For GSTP1 gene polymorphism, a 3-fold increase in CRC risk was observed with a high frequency of meat consumption (OR adjusted for sex and age = 3.4, 95% CI: 1.4–8.1). In the case of GSTT1 gene polymorphism, the increase in risk of CRC was not statistically significant (OR adjusted for sex and age = 1.9, 95% CI: 0.4–8.5). Conclusions: The frequency of red meat intake in non-smokers increases the risk of colon cancer in the case of GST gene polymorphisms.
Acute Supplementation with Nitrate-Rich Beetroot Juice Causes a Greater Increase in Plasma Nitrite and Reduction in Blood Pressure of Older Compared to Younger Adults
Authors: Stanaway Luke , Rutherfurd-Markwick Kay , Page Rachel , Wong Marie , Jirangrat Wannita , Teh Koon Hoong , Ali Ajmol
Published: July 2019

Nitrate-rich beetroot juice supplementation has been shown to improve cardiovascular and cognitive function in younger and older adults via increased nitric oxide production. However, it is unclear whether the level of effects differs between the two groups. We hypothesized that acute supplementation with nitrate-rich beetroot juice would improve cardiovascular and cognitive function in older and younger adults, with the potential for greater improvements in older adults. Thirteen younger (18–30 years) and 11 older (50–70 years) adults consumed either 150 mL of nitrate-rich beetroot juice (BR; 10.5 mmol nitrate) or placebo (PL; 1 mmol nitrate) in a double-blind, crossover design, 2.25 h prior to a 30-min treadmill walk. Plasma nitrate and nitrite concentrations, blood pressure (BP), heart rate (HR), cognitive function, mood and perceptual tests were performed throughout the trial. BR consumption significantly increased plasma nitrate (p < 0.001) and nitrite (p = 0.003) concentrations and reduced systolic BP (p < 0.001) in both age groups and reduced diastolic BP (p = 0.013) in older adults. Older adults showed a greater elevation in plasma nitrite (p = 0.038) and a greater reduction in diastolic BP (p = 0.005) following BR consumption than younger adults. Reaction time was improved in the Stroop test following BR supplementation for both groups (p = 0.045). Acute BR supplementation increased plasma nitrite concentrations and reduced diastolic BP to a greater degree in older adults; whilst systolic BP was reduced in both older and younger adults, suggesting nitrate-rich BR may improve cardiovascular health, particularly in older adults due to the greater benefits from reductions in diastolic BP.
Airway Epithelial Derived Cytokines and Chemokines and Their Role in the Immune Response to Respiratory Syncytial Virus Infection
Authors: Glaser Lena , Coulter Patricia J. , Shields Michael , Touzelet Olivier , Power Ultan F. , Broadbent Lindsay
Published: July 2019

The airway epithelium is the primary target of respiratory syncytial virus infection. It is an important component of the antiviral immune response. It contributes to the recruitment and activation of innate immune cells from the periphery through the secretion of cytokines and chemokines. This paper provides a broad review of the cytokines and chemokines secreted from human airway epithelial cell models during respiratory syncytial virus (RSV) infection based on a comprehensive literature review. Epithelium-derived chemokines constitute most inflammatory mediators secreted from the epithelium during RSV infection. This suggests chemo-attraction of peripheral immune cells, such as monocytes, neutrophils, eosinophils, and natural killer cells as a key function of the epithelium. The reports of epithelium-derived cytokines are limited. Recent research has started to identify novel cytokines, the functions of which remain largely unknown in the wider context of the RSV immune response. It is argued that the correct choice of in vitro models used for investigations of epithelial immune functions during RSV infection could facilitate greater progress in this field.
Repurposing Butenafine as An Oral Nanomedicine for Visceral Leishmaniasis
Authors: Bezerra-Souza Adriana , Fernandez-Garcia Raquel , Rodrigues Gabriela F. , Bolas-Fernandez Francisco , Dalastra Laurenti Marcia , Passero Luiz Felipe , Lalatsa Aikaterini , Serrano Dolores R.
Published: July 2019

Leishmaniasis is a neglected tropical disease affecting more than 12 million people worldwide, which in its visceral clinical form (VL) is characterised by the accumulation of parasites in the liver and spleen, and can lead to death if not treated. Available treatments are not well tolerated due to severe adverse effects, need for parenteral administration and patient hospitalisation, and long duration of expensive treatments. These treatment realities justify the search for new effective drugs, repurposing existing licensed drugs towards safer and non-invasive cost-effective medicines for VL. In this work, we provide proof of concept studies of butenafine and butenafine self-nanoemulsifying drug delivery systems (B-SNEDDS) against Leishmania infantum. Liquid B-SNEDDS were optimised using design of experiments, and then were spray-dried onto porous colloidal silica carriers to produce solid-B-SNEDDS with enhanced flow properties and drug stability. Optimal liquid B-SNEDDS consisted of Butenafine:Capryol 90:Peceol:Labrasol (3:49.5:24.2:23.3 w/w), which were then sprayed-dried with Aerosil 200 with a final 1:2 (Aerosil:liquid B-SNEDDS w/w) ratio. Spray-dried particles exhibited near-maximal drug loading, while maintaining excellent powder flow properties (angle of repose <10°) and sustained release in acidic gastrointestinal media. Solid-B-SNEDDS demonstrated greater selectivity index against promastigotes and L. infantum-infected amastigotes than butenafine alone. Developed oral solid nanomedicines enable the non-invasive and safe administration of butenafine as a cost-effective and readily scalable repurposed medicine for VL.
Applying Contemporary Management Principles to Implementing and Evaluating Value-Added Pharmacist Services
Authors: Desselle Shane P. , Moczygemba Leticia R. , Coe Antoinette B. , Hess Karl , Zgarrick David P.
Published: July 2019

Value-added pharmacy services encompass traditional and emerging services provided by pharmacists to individual and entire populations of persons increasingly under the auspices of a public health mandate. The success of value-added pharmacy services is enhanced when they are carried out and assessed using appropriate theory-based paradigms. Many of the more important management theories for pharmacy services consider the “servicescape” of these services recognizing the uniqueness of each patient and service encounter that vary based upon health needs and myriad other factors. In addition, implementation science principles help ensure the financial viability and sustainability of these services. This commentary reviews some of the foundational management theories and provides a number of examples of these theories that have been applied successfully resulting in a greater prevalence and scope of value-added services being offered.