bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic cerebral autoregulation after acute cigarette smoking in non‐smokers and habitual smokers
Authors: Peebles Karen C , Horsman Helen M , Tzeng Yu‐Chieh 
Published: June 2021

IntroductionCigarette smoking is associated with an increased risk of stroke in a dose dependent manner. Impaired baroreceptor function, associated with hypertension and increased blood pressure (BP) variability, offers one potential mechanism for smoking‐induced stroke risk. However, studies to date have not assessed whether smoking impairs dynamic cerebral autoregulation (dCA) or the interplay between dCA and baroreflex function in smokers. Thus, this study examined the impact of acute and chronic cigarette smoking on dCA and baroreflex function.MethodsWe recruited 17 non‐smokers and 15 habitual smokers. Transfer function analysis was used to examine dCA and baroreflex sensitivity before and immediately after acute smoking (a single cigarette) during spontaneous breathing.ResultsThere were no between‐group differences in dCA metrics (gain, phase and coherence) or low frequency baroreflex gain at baseline. However, both groups, showed a decrease in transfer function gain and coherence and increase in phase, after acute smoking, suggesting improved dCA. This increase in dCA was accompanied by a reduction in baroreflex gain, and increase in BP variability.ConclusionThese novel findings suggest that an increase in dCA counteracts the impact of impaired baroreflex function, potentially buffering the delicate cerebral vessels from the increase in BP variability after acute smoking.
Supplementation with phosphatidylcholine during suckling improves the immune response of the offspring
Authors: Lewis Erin Diane , Goruk Susan , Curtis Jonathan M , Jacobs René L , Field Catherine J 
Published: June 2021

Choline is essential during suckling for the development of the offspring. In the Alberta Pregnancy Outcomes and Nutrition cohort, the major forms of dietary choline were phosphatidylcholine (PC) and free choline. These forms are metabolized differently and this study was conducted to determine the effect of different forms of maternal dietary choline on immune development in the suckled offspring. Lactating dams (n=5/group) were randomized to nutritionally complete, isocaloric, high fat (20% w/w) diets of similar fatty acid compositions, containing 1.0 g/kg choline as free choline (C) or PC (PC) and 2 pups from each litter were pooled to assess the effect of diet on splenocyte function. Diet did not affect growth or the number and relative % of T or B cells in spleen. PC pups had a higher (1.56X) proportion of activated cytotoxic T cells (CD8+CD71+) compared to C pups (p<0.05). When stimulated ex vivo with Concanavalin A, cells from PC pups produced more IL‐2 (1.7X), IL‐6 (2.6X), and IFN‐γ (2.4X) compared to C pups (p<0.05). Cells from PC pups produced more IL‐6 (2.1X) and TNF‐α (1.4X) compared to C pups after stimulation with lipopolysaccharide (p<0.05). Findings suggest that providing choline in the maternal diet as PC promotes T cell maturation and function in the offspring during a critical period of immune development.Grant Funding Source: WCHRI Studentship, NSERC, Alberta Egg Producers
CCN1/Cyr61 regulates Sonic Hedgehog Signaling through Activation of Notch‐1 in Pancreatic Carcinogenesis: A Novel Targeting Pathway for Pancreatic Cancer Therapy
Authors: Haque Inamul , De Archana , Majumder Monami , Mehta Smita , McGregor Douglas , Banerjee Sushanta K , Van Veldhuizen Peter , Banerjee Snigdha 
Published: June 2021

CCN1 is a member of the CCN family of growth factors. It is associated with the development of various cancers including pancreatic ductal adenocarcinoma (PDAC). Previously we found CCN1 as an important factor in determining PDAC aggressiveness as it promotes epithelial to mesenchymal transition, tumor stemness, in vitro migration and tumorigenicity in xenograft model, possibly through the regulation of multiple miRNAs that are known to link with the progression of cancers and survival and the maintenance of cancer stem cells. CCN1 mRNA and protein expression was intensified with disease progression. However, biochemical activity and the molecular targets of CCN1 in pancreatic cancer cells are unknown. Our objective was to see whether CCN1 regulates the Sonic Hedgehog (SHh) signaling pathway, which is associated with the PDAC progression and poor prognosis. SHh regulation by CCN1 in pancreatic cancer cells is mediated through the active Notch‐1. Notably, active Notch‐1is recruited by CCN1 in these cells via the inhibition of proteasomal degradation results in stabilization of the receptor. Moreover, the functional role of CCN1 could be mediated through the interaction with the αvβ3 integrin receptor. These extensive studies propose that targeting CCN1 can provide a new treatment option for patients with pancreatic cancer since blocking CCN1 simultaneously blocks Notch1 and SHh signaling pathways.This work was supported by VA Merit Review Grants (Sushanta K. Banerjee and Snigdha Banerjee)
Gene‐Environment Interaction between Twist and Thyroid Hormone Results in Extreme Craniosynostotic Phenotypes in Mice
Authors: Parsons Trish Elizabeth , Weinberg Seth Michael , Elsalanty Mohammed , Khaksarfard Kameron , Yu Jack Chungkai , Cray James 
Published: June 2021

Craniosynostosis (CS) is the premature fusion of one or more cranial sutures; it can both hinder the growth of the brain and result in severe craniofacial dysmorphology. Although several genes have been implicated with CS, it is unclear how these genotypes lead to widely variable phenotypes. One possibility is gene‐environment interaction. A CDC study found several environmental risk factors associated CS, including maternal hyperthyroidism. We hypothesize that predisposed genotypes will result in more extreme CS phenotypes when exposed to thyroid hormone. To test this we introduced thyroxine to the maternal environment of a genetic CS mouse model, Twist+/−. TWIST has been linked with CS and this model exhibits variable phenotypic expression of CS. Twist+/− and WT control pregnant dams were given thyroxine‐laced water at E13, before suture formation. We sacrificed neonates at P15 and scanned the skulls using μCT. We collected landmarks from the 3D reconstructions and analyzed them using geometric morphometrics. Our preliminary results show that thyroxine has a clear affect on the shape of both Twist+/− and WT skulls and it affects the two groups differently. Exposed Twist+/− mice have higher cranial vaults, wider calvaria, shorter maxilla lengths and wider midfaces compared to both WT and Twist+/− unexposed mice; these shape changes are similar to those associated with CS.Grant Funding Source: Cleft Palate Foundation
Specificity Factor 1 (Sp1) Mediates Transcriptional Induction of Atp7a During Hypoxia in Rat Intestinal Epithelial (IEC‐6) Cells
Authors: Xie Liwei , Collins James F. 
Published: June 2021

Genes with GC‐rich promoters were preferentially induced in the rat intestinal epithelium during iron deficiency. Moreover, promoters of iron homeostasis‐related genes (e.g. Dmt1, Dcytb) contain evolutionarily conserved GC‐rich sequences. The Menkes Copper ATPase (Atp7a) gene was strongly induced during iron deficiency, and we previously demonstrated that Atp7a was coregulated with iron transport‐related genes by HIF2α. In this study, we sought to test the role of Sp1 in transcriptional regulation of Atp7a, as phylogenetic footprinting revealed conserved GC‐rich sequences in the Atp7a promoter. An Sp1 inhibitor (mithramycin) reduced Atp7a and iron transport‐related gene expression. Sitedirected mutagenesis of a basal −224 bp promoter construct showed that several GC‐rich sites participated in the HIF2α‐mediated induction of promoter activity in IEC‐6 cells. Moreover, mithramycin also blocked induction of Atp7a and iron transport genes by hypoxia. We also show that phosphorylation of Sp1 increased in IEC‐6 cells exposed to hypoxia; Sp1 is known to be regulated by phosphorylation, which increases DNA binding and trans‐activation properties. Further, chromatin immunoprecipitation (ChIP) assay indicated that Sp1 binds to the Atp7a promoter. Current data thus suggest that synergistic interactions between Sp1 and HIF2α mediate the induction of Atp7a expression during hypoxia/iron deficiency.Grant Funding Source: NIH
Correlation Network Analysis in Evaluating Dietary Milk Polar Lipids in A Mouse Model of Diet‐induced Obesity
Authors: Zhou Albert Lihong , Ward Robert , Lefevre Michael 
Published: June 2021

Leaky gut, endotoxemia, inflammation and obesity are interrelated events during the development of diet‐induced obesity (DIO). To study the effects of dietary milk polar lipids on those relationships, 3 groups of B6 mice were fed for 15 weeks: (1) AIN‐93G based moderately high fat diet (CO); (2) CO with gangliosides; (3) CO with phospholipids. Gut integrity and body fat were measured 6 and 9 times. Plasma cytokines & lipids were tested 3 times. Final measurements included tissue lipids profiles, liver lipid gene expression, and tight junction proteins in gut mucosa. Correlation matrices of parameters were subjected to network analysis by Cytoscape. Forced‐directed layouts and community clusters were produced for networks, which revealed general patterns of the effects of dietary polar lipids. Higher connectivity among parameters in network layouts may indicate more integrative and cohesive connections among biological functions. A decrease in parameter connectivity was observed after initiation of the high fat feeding. Based on networks patterns, dietary polar lipids appear to have negative effect on parameters measured during early phase of DIO and positive effect on all parameters after DIO. In conclusion, correlation network analysis is a powerful tool in revealing general patterns of the effects of dietary treatments between multiple biological parameters.Grant Funding Source: Western Dairy Center
Development and validation of the US Healthy Food Diversity (HFD) Index: a novel measure of dietary variety, quality, and proportionality
Authors: Vadiveloo Maya , Mijanovich Todor , Dixon L Beth , Parekh Niyati 
Published: June 2021

Imprecise measurement of dietary variety may confound associations between variety and obesity. The intent of this study was to develop the novel US HFD index to measure total dietary variety while including measures of dietary quality and proportionality delineated in the 2010 Dietary Guidelines for Americans (DGA).Two 24‐hour recalls from the 2003–2006 National Health and Nutrition Examination Survey were merged with the My Pyramid Equivalent databases to obtain food‐group level data. The US HFD was generated with the equation HFD=(1 − ∑s2i)* hv where s= share by volume of each food in the diet and hv=health value of the diet, per the 2010 DGA. The US HFD ranges from 0 and 1‐ 1/n; eating a variety of foods in proportions indicated by the DGA maximizes the score (~1). The NCI Method was used to estimate usual intake of the 26 US HFD food groups and sample‐weighted means, standard errors, and correlations were generated with SAS 9.3.Reliable dietary data from 7,470 non‐pregnant adults ages 20+ were analyzed. US HFD scores ranged from 0.25–0.51. Mean scores were 0.38±0.002 in men vs. 0.40±0.001 in women and 0.38±0.002 in smokers vs. 0.39±0.001 in non‐smokers. Energy‐adjusted US HFD scores correlated with the mean probability of adequacy for 15 nutrients (ρ=0.50 in men and ρ=0.51 in women, p<0.001). The US HFD is a valid measure of dietary variety and may help clarify associations between variety and obesity in future research.Grant Funding Source: American Heart Association Founders Affiliate Predoctoral Fellowship (12PRE9320023)
Teaching medical students how to walk the walk: Will improving student dietary habits change patient counseling perceptions?
Authors: Kay Danielle , Abu‐Shamat Layla , Leong Benjamin , Monlezun Dominique , Sarris Leah , Harlan Timothy 
Published: June 2021

Howe et al. (2010) found that residents and physicians fail to meet dietary guidelines on fruit and vegetable (F/V) intake and that personal dietary habits had no effect on perceived efficacy of patient counseling. At Tulane University School of Medicine (TUSOM), a survey was sent out to assess students’ dietary habits, prior nutritional experience, and perceptions of nutritional counseling competency and counseling importance. Only 51.9% of respondents eat F/V on average at least once daily. Also, there is no significant difference in perceived competency in counseling overweight patients on weight loss strategies (p=0.36) and in perceived importance of nutritional counseling at each visit (p=0.17) between students with daily F/V consumption and students with less F/V intake. Overall, student F/V intake was less than dietary recommendations. There was also no correlation between F/V intake and perceived nutritional counseling competency and importance. We hope to assess the impact of novel medical nutrition curriculum on students’ dietary habits and whether this intervention will affect counseling efficacy and patient compliance. Research support: Tulane University Center for Culinary MedicineGrant Funding Source: Tulane University Center for Culinary Medicine
The interaction between physical activity and obesity gene variants in association with BMI: Does the obesogenic environment matter?
Authors: Richardson Andrea S , North Kari E , Graff Mariaelisa , Young Kristin L , Mohlke Karen L , Lange Ethan M , Lange Leslie A , Harris Kathleen M , Gordon‐Larsen Penny 
Published: June 2021

BackgroundLittle is known about how obesity SNPs interact with moderate to vigorous physical activity (MVPA) in relation to BMI during adolescence, accounting for the obesogenic environment.MethodsWe tested 43 SNP by MVPA interactions with BMI (measured heights and weights) using stepwise addition of obesogenic neighborhood factors in 8,028 respondents from the National Longitudinal Study of Adolescent Health (1996; ages 12–21). Multi‐level models were stratified by race: European Americans (EA; N=5,022), African Americans (AA; N=1,726), and Hispanic (HA; N=1,280), controlling for age, sex, current smoking, region, and hours of TV/video, with addition of: 1) physical activity resources: physical activity facilities, parks; 2) neighborhood infrastructure: green space, street connectivity; and 3) neighborhood social factors: neighborhood poverty, and crime.ResultsNine of 43 SNP × MVPA interactions were nominally significant (EA: 7, HA: 2), with larger estimated effects on BMI in adolescents with lower MVPA. For example, in EA, rs987237 was associated with a 1.02 unit higher BMI in adolescents with < 5 (b=1.02, CI: 0.6–1.5) versus ≥ 5 (b=0.271, CI: −0.001–0.6) bouts MVPA/week. Findings were robust after inclusion of neighborhood obesogenic covariates.ConclusionsThese findings suggest that MVPA may attenuate obesity susceptibility during adolescence independent of neighborhood context.Grant Funding Source: R01HD057194
Alternate day fasting when combined with endurance exercise reduces leptin but not adiponectin and resistin
Authors: Bhutani Surabhi , Klempel Monica C , Kroeger Cynthia M , Varady Krista A 
Published: June 2021

BackgroundAlternate day fasting (ADF), consisting of a feed day (24‐hour ad libitum food intake) alternated with a fast day (75% energy restriction), is effective in reducing body weight and modulating adipose tissue physiology. However, the ability of ADF in combination with endurance exercise to improve the above variables has never been tested.ObjectiveAccordingly, this study examined whether the combination of ADF plus exercise produces superior changes in body weight and plasma adipokine levels, when compared to each treatment alone.MethodsObese subjects (n=64) were randomized to 1 of 4 groups for 12 weeks: 1) combination (ADF + endurance exercise), 2) ADF, 3) exercise, or 4) control.ResultsBody weight was reduced (P < 0.05) by 7 ± 1 kg, 5 ± 1 kg, and 1 ± 1 kg, and fat mass decreased (P < 0.001) by 6 ± 1 kg, 4 ± 1 kg and 1 ± 1kg in the combination, ADF and exercise group, respectively. Fat free mass was retained in all groups. Adiponectin and resistin values did not change in any group post‐treatment. Leptin levels significantly decreased (P < 0.05) by 38 ± 10 ng/ml, 15 ± 6 ng/ml and 15 ± 6 ng/ml in the combination, ADF, and exercise group, respectively.ConclusionThese findings suggest that the combination of ADF plus exercise produces superior changes in body weight, body composition and leptin levels, when compared to each intervention alone.Grant Funding Source: American Heart Association Predoctoral Fellowship
Parent and child use of dietary supplements are associated
Authors: Dwyer Johanna T , Jacques Paul F , Rogers Gail T , Sempos Christopher , Bailey Regan L 
Published: June 2021

BackgroundLittle is known about the interaction between parents and children in dietary supplement (DS) use.ObjectiveDetermine if parental use of dietary supplements predicted child use.Methods4556 parent‐child pairs who responded to questions about DS use over the past 30 days and participated in the CAM supplement of the 2007 National Health Interview Survey. DS were categorized as multivitamin mineral (MVM) (2 or more vitamins +/or minerals) only; single vitamin or mineral DS (SVM) with or without use of MVM; non‐vitamin non‐mineral DS with or without use of MVM or SVM (NVNM) and DS nonusers. Prevalence of use and standard errors were calculated using SUDAAN PROC DESCRIPT to account for the complex sampling design and standardized to the 2000 census.ResultsIn the pairs, 46.4% of the parents and 36.6% of the children took DS, and use of MVM and SVM was much more common than NVNM. For parents who used any DS, fully 55% of their children used them as well. Among parents who used MVM, 50% of the children used MVM, for parents who used SVM, only 10% of the children used SVM and for parents who used NVNM, only 13% of the children used them.ConclusionParents who use DS are more likely to give them to their children than those who do not. In most cases the children took micronutrient DS (MVM and SVM). Parents who used NVNM were more likely to have children who used NVNM.Support: Office of Dietary Supplements, NIH, and Jean Mayer USDA HNRC on Aging at Tufts University
Effects of water‐based hand sanitizers and micronutrient powders along with nutrition and hygiene education to prevent infections and linear growth faltering among low birth weight infants in Bangladesh
Authors: Shafique Sohana , Jalal Chowdhury S.B. , Jolly Saira P. , Shikder Hasina , Sellen Daniel W. , Zlotkin Stanley 
Published: June 2021

ObjectiveTo measure the relative efficacy of Benzalkonium Chloride containing, water‐based hand sanitizers (HS) and multiple micronutrient powder (MNP) along with nutrition and hygiene education (NHE) to prevent infections and linear growth faltering among low birth weight (LBW) infants.MethodsProspective 2×2 factorial, cluster‐randomized trial, conducted among 467 full‐term LBW infants from 0–12 months (mo) in rural Bangladesh, using 48 clusters randomly assigned as follows: from 0–6 mo, i) NHE only or ii) NHE plus HS; from 6–12 mo, i) NHE only; ii) NHE plus HS; iii) NHE plus MNP (to be provided with complementary foods); and iv) NHE plus HS and MNP.ResultsDuring 0–6mo, the proportion of LBW infants with any infection was significantly lower in the ‘NHE plus HS’ group compared to the ‘NHE only’ group (P<0.001). Mean duration of diarrhea among LBW infants was significantly lower in the ‘NHE plus HS’ group compared to ‘NHE only’ (3.4±1.2 vs. 6.0±1.6 days, P<0.01). Upper respiratory tract infections and cough were also significantly lower in the ‘NHE plus HS’ group in comparison with ‘NHE only’ (29.8% vs. 33.0% and10.6% vs. 12.2%, P<0.05, for both).ConclusionsCaregiver use of hand sanitizers might effectively reduce infections among term LBW infants in the first six months of life.Grant Funding Source: Bill & Melinda Gates Foundation to FHI 360, through the Alive & Thrive Small Grants Program managed by UC Davis.
Neonatal dietary calcium alters mesenchymal stem cell differentiation potential in pigs
Authors: Li Yihang , Seabolt Brynn , Stahl Chad 
Published: June 2021

Neonatal Ca nutrition affects bone development and mesenchymal stem cell (MSC) activity; however, its effect on MSC differentiation potential has not been fully characterized. MSC were isolated from neonatal pigs fed either a Ca deficient, adequate, or excessive diet. After in vitro adipogenic induction, PPARG and AP2 expression was up‐regulated in MSC from Ca deficient (P<0.1) and Ca excess (P<0.05) groups. Under osteogenic induction, osteocalcin (OC) gene expression was depressed in MSC from Ca deficient pigs. To further evaluate the impact of Ca status on MSC activity, 20 individual colonies were obtained from each pig. From these colonies, we selected the most and least osteogenic (O+/O−) and the most and least adipogenic (A+/A−) clones based on functional staining. During osteogenesis, increased (P < 0.1) gene expression of Runx2 and OC was seen among O+ colonies. Increased expression of OC was seen among Ca adequate (P<0.01) and excess (P=0.07) colonies compared with the Ca deficient colonies. During adipogenesis, A+ colonies had greater expression (P < 0.1) of AP2 and LPL. No interaction between osteogenic or adipogenic capability and Ca status was seen. This suggests that the differences in adipocytic and osteogenic differentiation of MSC based on the Ca status of the pig is due to alterations in the number of highly osteogenic and adipogenic MSC in the heterogeneous population.Grant Funding Source: NC Agricultural Research Service
Global DNA hypomethylation in peripheral blood mononuclear cells as a biomarker of cancer risk
Authors: Guarini Patrizia , Udali Silvia , Pattini Patrizia , Moruzzi Sara , Girelli Domenico , Pizzolo Francesca , Martinelli Nicola , Olivieri Oliviero , Choi Sang Woon , Friso Simonetta 
Published: June 2021

DNA methylation is a reversible epigenetic phenomenon that can be modified by nutrients such as folate and influenced by the MTHFR677C>;T polymorphism in a gene‐nutrient interaction manner. In human cancer, global DNA hypomethylation is an almost universal finding.Peripheral blood mononuclear cells (PBMCs) are easily accessible in humans and our aim was to test PBMCs DNA methylation according to the folate‐MTHFR677C>;T polymorphism interaction, as a potential biomarker for cancer risk.Global DNA methylation was measured in PBMCs of 68 subjects with cancer history at enrollment and 62 with cancer after eight‐year follow‐up compared to age‐and sex‐matched controls (68 at enrollment, 58 at follow‐up).Cancer subjects had lower plasma folate concentrations (P=0.003), higher frequency of MTHFR677TT (P=0.013) and lower PBMCs‐ DNA methylation than controls (P<0.0001). A DNA methylation threshold of 4.74% categorized cancer patients from controls. Subjects with cancer at follow‐up had at enrollment lower DNA methylation than controls (P<0.0001).The association of MTHFR677TT and low plasma folate showed the lowest DNA methylation levels (4.39%). Cancer deaths had a lower DNA methylation compared with other cause deaths (P=0.015) and the survivors had an increased DNA methylation compared to cancer (P=0.004).Low global DNA methylation in PBMCs may be a useful predictive biomarker of cancer.