bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Ezetimibe on Low‐and High‐Density Lipoprotein Subclasses in Sitosterolemia
Authors: Othman Rgia , Myrie Semone , Mymin David , Merkens Louise , Roullet Jean‐Baptiste , Steiner Robert , Jones Peter 
Published: June 2021

Sitosterolemia (STSL) is a rare sterol disease manifested by very high plasma phytosterols (PS) with normal to high total cholesterol (TC) levels and increased atherosclerosis risk. Low density lipoprotein (LDL), intermediate density lipoprotein (IDL) and very lowdensity lipoprotein (VLDL) cholesterols are proatherogenic while high density lipoprotein (HDL) cholesterol is antiatherogenic. Ezetimibe (EZ), a sterol absorption inhibitor, can reduce plasma PS and TC levels in STSL but its effect on lipoprotein subclasses has not been studied. We evaluated the effect of EZ on lipoprotein subclasses in STSL patients (pts, n=8) taken off EZ for 14 wks then placed on EZ (10 mg/d) for 14 wks. Serum total lipids and subfractions were measured enzymatically or with the Lipoprint system. Data (mean±SEM) were analyzed by paired t‐test. EZ reduced serum TC (‐13±4%, p=0.02), VLDL (‐24±4%, p=0.002) and total LDL (‐17±6%, p=0.03) levels vs off EZ. Reduced LDL values were due to decreased IDLB and C (‐22±7 and ‐21±8%, p<0.05), not to large, buoyant LDL subclasses (LDL1: ‐8±8%, p=0.23 and LDL2: +35±55%, p=0.17). LDL size did not change with EZ (275±0 vs 274±1 Å, p=0.18). EZ increased HDL levels (26±8%, p=0.008) due to increased intermediate (34±14%, p=0.02) and large (33±16%, p=0.06) HDL subclasses. These data suggest EZ can favorably affect LDL and HDL subfractions distribution, thus providing potential clinical benefit in STSL beyond reducing TC and PS accrual.Funded by NIH and CIHR
Generation of Superoxide and Toxicity of Amino Alcohols to K562 and HepG2 Cancer Cells
Authors: Shastri Anuradha , Boylan Mallory , Spallholz Julian 
Published: June 2021

Purpose:In our previous studies we have established that some water soluble aliphatic alcohols redox cycle generating superoxide. In the current study, we used the lucigenin chemiluminescence (CL) assay to determine if the amino alcohols (AA); 3‐Amino‐1‐propanol (3A1P), 4‐Amino‐1‐butanol (4A1B), 5‐Amino‐1‐pentanol (5A1P) and 6‐Amino‐1‐hexanol (6A1H) redox cycled in the presence of reduced glutathione. Cytotoxicity of the AA was assessed against the Chronic Myeloid Leukemia K562 and the Hepatocellular Carcinoma HepG2 cell lines.Methods:Stock solutions (5 mg/mL) of the AA corresponding to 62.5, 125, 250, 500 μg of the hydroxyl moiety were added to the CL cocktail. CL was integrated over 30 sec intervals at 36°C (n=20).K562 and HepG2 cells were treated and incubated for 24, 48 and 96 hours with concentrations of 220, 240, 260, 280, 300 μg of the AA. Light microscopy and MTT assay were used to measure cell viability. Dihydroethidium (DHE) was used to detect intracellular superoxide generation.Results:The CL assays indicated that 5A1P redox cycled most, followed by 4A1B in a dose dependent manner. For both cell lines, the MTT assay showed that compared to control, AA treated cells showed reduced cell viability in a dose dependent manner. At 300 µg, at 48 hours 6A1H produced maximum cell death K562 (∼94%) and HepG2 (∼90%). The DHE assay indicated generation of superoxide in the cell.ConclusionsAll of the AA tested were shown to generate superoxide in vitro as determined by the CL. Both light microscopy of cell morphology and MTT cell viability assay showed that all the AA caused cell death, presumed to be due to their ability to redox cycle generating reactive oxygen species as in the CL assay in the absence of cells. The DHE assay confirmed the intracellular superoxide generation in treated cells.
Toddler Feeding Practices in Early Head Start and Migrant/Seasonal Early Head Start Mothers
Authors: Voorheis Grace , Papathakis Peggy , Nicholson Lisa 
Published: June 2021

ObjectiveMeasure baseline data on parental feeding practices of low‐income, Latina mothers of toddlers (1‐3 years) enrolled in Head Start in order to develop parent education.MethodsSixty‐six mothers in Early Head Start (EHS, n=25) and Migrant/Seasonal Early Head Start (MSHS, n=41) completed a 24 item Likert scale (1‐5 with 1=Never/Not confident) to assess self‐efficacy, behavior and intentions regarding 4 domains of toddler feeding practice. These were scheduling, self‐regulation, indulging, and parental role modeling. Mean Likert scores for each question were analyzed by subgroup.ResultsMothers in both groups were similar in their parental feeding practices; they had low self‐efficacy for allowing their child to play with food and high self‐efficacy for discerning when their child was full. Both groups indicated they kept a regular meal schedule more frequently than a snack schedule and infrequently encouraged their child to eat more when he/she has indicated fullness. Self‐efficacy regarding avoiding indulging their child's favorite foods was higher in EHS mothers than MSHS mothers (p=0.041). For MSHS mothers, indulging their toddler with sweets (p=0.024) and role modeling eating fruits (p=0.014) were significantly more frequent than in EHS mothers. EHS mothers allowed their child to snack all day more frequently than MSHS mothers (p=0.013).ConclusionIndulging in favorite foods appears more common in families in MSHS than in EHS. Frequent consumption of fruit is higher in MSHS than EHS families, potentially because these mothers are employed in fruit‐picking industry. Future educational interventions should focus on encouraging authoritative feeding styles to avoid indulgence and maintain a schedule throughout the day.
Self‐Efficacy is Associated with Healthy Eating Behaviors for Fifth Grade Students
Authors: Hall Elisha , Chai Weiwen , Koszewski Wanda , Albrecht Julie 
Published: June 2021

ObjectiveTo assess the relationships between three integral constructs of the Social Cognitive Theory (SCT), knowledge, self‐efficacy, and behavior, and specific self‐efficacy and behavior variables for healthy eating among fifth grade students.Methods: Ninety‐eight fifth grade students recruited from four local elementary schools completed the Healthy Habits Survey, a 37‐item nutrition and physical activity survey covering knowledge, self‐efficacy, behavior and demographics. Relationships between knowledge, self‐efficacy, and behavior were assessed using Pearson Correlation Coefficients. Differences in behavior and knowledge scores between participants with high and low self‐efficacy were examined using a t‐test.Results: Total scores for self‐efficacy and behaviors were positively correlated (r=0.32, P=0.002); however, total knowledge scores were not associated with self‐efficacy (r=0.02, P=0.88) or behavior scores (r=0.19, P=0.10). In terms of specific eating behaviors, more than two thirds of fifth grade students reported that they did not eat any fruits or vegetables or ate them only once on a typical day, aligning with trends seen nationally on low fruit and vegetable consumption in children.ConclusionsResults indicate that self‐efficacy is significantly associated with behavior, therefore should be integrated when creating interventions for behavior change. In addition, specific behaviors such as fruit and vegetable consumption continue to fall below dietary recommendations and need continued programming to target this issue.*This research was supported by USDA NIFA Growing Healthy Kids through Health Communities grant; 2011‐67001‐30011.
Serum fatty acids concentrations are associated with plasma adipokines during pregnancy
Authors: Lepsch Jaqueline , Pinto Thatiana , Farias Dayana , Franco‐Sena Ana , Rebelo Fernanda , Lima Natália , Vaz Juliana , Cunha Marcelo , Kac Gilberto 
Published: June 2021

ObjectiveTo investigate if serum concentrations of total saturated (SFA), polyunsaturated (PUFA) and its fractions are associated with plasma adiponectin and leptin concentrations during pregnancy.MethodsProspective cohort of 221 pregnant women followed at 5‐13th, 20‐26th and 30‐36th gestational weeks. Blood samples were collected after 12 hours of fasting. FA concentrations were determined using fast gas‐liquid chromatography. Plasma adiponectin (U/ml) and leptin (ng/dl) were estimated using ELISA. Statistical analyses included mean concentrations of the adipokines according to tertiles of FA distribution and longitudinal linear mixed‐effect models, adjusted for BMI, time and total energy intake.ResultsMean adiponectin was lower in the 3th tertile of SFA when compared to the 2nd and 1st tertiles (2nd trimester: 1st tertile=11.4; 2nd=10.4; 3rd=9.26). Mean of leptin was higher in the 3th tertile of SFA compared to the 2nd and 1st tertiles (2nd trimester: 1st tertile=27.5; 2nd=33.3; 3rd=36.1). The serum concentrations of SFA (β=‐0299, p=0.022) and its fractions were negative and significantly associated with adiponectin [(14:0; β=‐0.021, p=0.012); (16:0; β=‐0.004, p=0.002); (18:0; β=‐0.009, p=0.051)]. Total PUFA n‐6 (β=0.003, p<0.001) and 18:2n6 (β=0.002, p=0.005) were positively associated with adiponectin. SFA (β=1.092, p=0.017), 14:0 (β=0.092, p=0.002) and 20:3n‐6 (β=0.055, p=0.006) was positively associated with leptin.ConclusionsTotal serum SFA and fractions were negatively associated with adiponectin and positively associated with leptin and total n‐6 PUFA was positively associated with adiponectin during pregnancy.
Cardiometabolic Profiles and Gene Expression Following Fish Oil Supplementation: Is There a Role for FADS Genotypes?
Authors: Roke Kaitlin , Zulyniak Michael , Gerling Christopher , Whitfield Jamie , Spriet Lawrence , Mutch David 
Published: June 2021

Consumption of omega‐3 fatty acids (FAs) modifies cardiometabolic risk factors in hyperlipidemic and diabetic individuals; however, their effects in young healthy adults are unclear. We examined the impact of fish oil supplements on blood cardiometabolic markers, FA composition, eicosanoid profiles and gene expression. We then examined whether these endpoints varied with an individual's fatty acid desaturase (FADS) genotype. Young male adults (18 – 25 yrs) consumed daily fish oil supplements (up to 3g omega‐3 FAs) for 12 weeks. Significant reductions in blood triglycerides were seen by week 12. Paradoxically, two omega‐6 derived eicosanoids (PGF2α and TXB2) were increased with supplementation. Whole blood gene expression revealed no differences in key genes regulating eicosanoid production, i.e., ALOX5, ALOX12, ALOX15, COX‐2 and iPLA2. FA analysis showed increases in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content in serum and red blood cells (RBCs), and decreases in arachidonic acid (AA). Compared to major allele carriers, individuals with FADS minor allele variants experienced greater increases in EPA levels in serum and RBCs during supplementation. There were no genotype differences for DHA or AA levels. Collectively, our results showed that fish oil supplements alter the eicosanoid profile independent of changes in gene expression. Additionally, we demonstrated that changes in FA levels after supplementation are influenced by an individual's FADS genotype. Further investigations regarding the relationship between fish oil supplements, eicosanoid profiles, and FADS genotype are warranted.Grant Funding Source: Supported by NSERC
Effect of High‐Dose Vitamin D on Antimicrobial Peptides in Ventilator‐Dependent Critically Ill Patients
Authors: Jones J , Alvarez J , Han J , Hao L , Chiang E , Brown L , Tangpricha V , Martin G , Ziegler T 
Published: June 2021

ObjectiveVitamin D has been shown to influence indexes of immunity, including antimicrobial peptides (AMPs). Vitamin D deficiency is common in critical illness, but the impact of vitamin D status or the response to treatment with high‐dose vitamin D on AMPs in this population is unknown. Thus, we evaluated the impact of two doses of vitamin D3 (D3) versus placebo on AMPs in ventilated, critically ill subjects.MethodsThirty critically ill, ventilated subjects were enrolled in a randomized, double‐blind controlled trial of enteral high‐dose D3 (total dose = 250,000 IU or 500,000 IU) given in divided doses over 5 consecutive days. Plasma 25‐hydroxyvitamin D [25(OH)D] was measured by chemiluminescence. Plasma levels of AMPs, cathelicidin (LL‐37) and human beta‐defensin‐2 (hBD‐2), were measured by ELISA, and PBMC LL‐37 mRNA by quantitative PCR at baseline, days 7 and 14 after study entry. Descriptive statistics (mean ± SD), Spearman correlations, and repeated measures ANOVA were used for analysis.ResultsThe study population was 60% male, mean age was 63.5 ± 17.3 yrs, and 43% were vitamin D deficient at baseline. D3 administration significantly increased plasma 25(OH)D levels from baseline to day 14 vs placebo (500,000 IU: 20.0 ± 7.3 to 62.4 ± 16.7 ng/mL; 250,000 IU: 23.2 ± 7.8 to 50.4 ± 29.4 ng/mL; placebo: 21.5 ± 12.2 to 21.5 ± 11.3 ng/mL, respectively; p < 0.01). Baseline 25(OH)D levels were unrelated to baseline AMP indexes. Plasma LL‐37, hBD‐2, and PBMC LL‐37 mRNA did not change over time in any group.ConclusionsBaseline vitamin D status did not influence plasma LL‐37 and hBD‐2 levels or PBMC LL‐37 mRNA in critically ill, ventilated adults. High‐dose D3 administration markedly increased 25(OH)D levels, but did not alter production of AMPs.
The Impact of High‐Dose Vitamin D on Hemoglobin Concentrations in Critical Illness
Authors: Smith Ellen , Jones Jennifer , Han Jenny , Alvarez Jessica , Chiang Ellen , Martin Greg , Ziegler Thomas , Tangpricha Vin 
Published: June 2021

ObjectiveAnemia and vitamin D deficiency are highly prevalent in critically ill patients, and vitamin D may be involved in the regulation of iron recycling. The purpose of this study was to examine the impact of vitamin D therapy on hemoglobin concentrations in critically ill patients.MethodsWe conducted a secondary analysis of a randomized, double‐blinded, placebo‐controlled trial of high‐dose vitamin D3 (D3) therapy in critically ill adults requiring mechanical ventilation (N=30). Participants were randomized to receive a total enteral dose of 500,000 IU D3, 250,000 IU D3, or placebo administered over 5 days. Blood was drawn weekly throughout hospitalization for up to 4 weeks. Linear mixed effects models were used to assess change in hemoglobin concentration by treatment group over time.ResultsThe prevalence of anemia at baseline was 93.3%. Baseline mean hemoglobin and plasma 25‐hydroxyvitamin D concentrations were 9.7 g/dL (SD=1.9) and 21.4 ng/mL (SD=9.1), respectively, and did not differ significantly across treatment groups. In the 250,000 IU D3 group, change in hemoglobin over time did not differ from placebo (P=0.5). However, in the group who received 500,000 IU D3, hemoglobin concentrations increased by 0.8 g/dL (SE=0.3) per week (P=0.005).ConclusionIn this population of critically ill patients, treatment with 500,000 IU D3 over 5 days increased hemoglobin concentrations during hospitalization, while no significant change in hemoglobin was observed in the 250,000 IU D3 or placebo groups. These findings support a role for vitamin D in improving hemoglobin concentrations in critical illness, which should be confirmed in larger studies.Funding: T32 DK7734‐17, R21 HL110044
Effects of Ester‐C®and Ascorbic Acid on Gastrointestinal Outcomes: A Randomized, Double‐Blind Trial
Authors: Ye Qian , Combs Maile , Mitmesser Susan 
Published: June 2021

BackgroundOptimum vitamin C intake is not always attainable solely via food consumption, therefore supplementation may be desirable. However, vitamin C supplementation is not without notable gastrointestinal discomfort resulting from its acidic nature, which may affect overall quality of life.ObjectiveTo compare the effects of Ester‐C® (EC) and Ascorbic Acid (AA) on gastrointestinal symptoms and quality of life in subjects with acid‐sensitivity.MethodsIn this double‐blind, cross‐over study, 50 healthy adults with acid‐sensitivity were randomized to receive vitamin C (1000 mg for Day 1‐5, 2000 mg for Day 6‐10) provided by either AA or EC. Gastrointestinal side effects as measured by Gastrointestinal Symptom Rating Scale (GSRS) and the associated changes in quality of life as measured by Medical Outcomes Short Form‐36 (SF‐36) were assessed.ResultsAn intention‐to‐treat analysis was conducted on 50 subjects (11 males, 39 females). After ten days of treatment, AA resulted in significant worsening of Abdominal pain (p=0.02), Diarrhea (p=0.047), and total GSRS score (p=0.019), while there were no significant changes in EC group. The Role Physical and Bodily Pain scores were significantly better in EC group compared to AA group over the ten‐day period (p = 0.004 and 0.008, respectively).ConclusionEster‐C® is better tolerated than Ascorbic Acid in individuals with acid‐sensitivity.
Sulforaphane Reduces Inflammatory Gene Expression in Microglia from Aged Mice
Authors: Townsend Brigitte , Rytych Jennifer , Johnson Rodney 
Published: June 2021

Increased oxidative stress resulting from heightened microglial activation is associated with age‐related cognitive impairment, neurodegenerative disease, and response to immune stimulus. The primary compensatory mechanism for neutralizing oxidative stress is through the nuclear factor E2‐related factor 2 (Nrf2) pathway which regulates transcription of antioxidant response element (ARE) genes. Here, BV2 cells and brain CD11b+ microglial cells isolated from young adult and aged mice were used to investigate the effects of sulforaphane (SFN), a potent Nrf2‐inducing bioactive, on ARE and inflammatory gene expression associated with increased age. We hypothesized that SFN would upregulate ARE genes in primary microglial cells and that this would attenuate elevated proinflammatory cytokine expression in microglia from aged mice. In support of our hypothesis, SFN upregulated antioxidant genes NAD(P)H dehydrogenase, quinone 1 (NQO1), heme oxygenase‐1 (HMOX1), and the modulatory subunit of glutamate‐cysteine ligase, modifier subunit (GCLM) in BV2 cells and primary microglia. Primary microglia from aged mice had higher expression of interleukin (IL‐)1β, IL‐6, and inducible nitric oxide synthase (iNOS) than adult controls, and SFN reduced IL‐1β and iNOS in microglia from aged mice. Taken together these data indicate that SFN is a potential therapeutic supplement that may be beneficial for reducing microglia‐mediated neuroinflammation and oxidative stress associated with aging.Supported by NIH RO1AG16710
Obesity‐associated Inflammation Contributes to Adipose Stromal Cells Pro‐fibrotic Phenotype
Authors: Springer N , van den Berg M , Seo B R , Fischbach C 
Published: June 2021

IntroductionObesity is linked to breast cancer pathogenesis and physical changes to the adipose microenvironment may be important. We have observed increased myofibroblasts, cells derived from adipose stromal cells (ASC) that deposit extracellular matrix (ECM), and a correlation with macrophagic inflammation in obese fat. Our objective is to assess a functional link between inflammation, ECM stiffness and ASC differentiation.MethodsBone marrow macrophages (BMM) or RAW 264.7 cells were cultured on hydrogels mimicking the mechanical properties of lean (1 kPa) or obese (10 kPa) adipose ECM. BMM morphology and response to LPS were judged by immunofluorescence. RAW 264.7‐conditioned media (CM) tested the effect of macrophage‐secreted factors on ASC (3T3‐L1) differentiation into adipocytes and myofibroblasts. Non‐CM and TGFβ served as controls. Adipocyte and myofibroblast differentiation were quantified by lipid droplet diameter and αSMA immunofluorescence, respectively.ResultsBMM cultured on 10 kPa v. 1 kPa gels had increased cytoplasmic extensions and actin stress fibers. BMM from 10 kPa gels trended to reduced iNOS expression post‐LPS, which was negated by inhibiting mechanosignaling. CM increased αSMA and reduced lipid droplet size (p<0.05). Myofibroblast differentiation was similar for both stiffnesses, but CM from 10 kPa gels reduced adipogenesis more (p<0.05) and comparably to TGFβ positive control.ConclusionsStiffness alters macrophage function and macrophage‐secreted factors promote myofibroblast and hinder adipocyte differentiation of ASC. Experiments are underway to confirm macrophage mechanosignaling as a mechanism.FundingNIH T32ODO011000 & 1R01CA185293, CMM U54CA143876
Mobile Handheld Devices Applications to Teach Rational Prescribing and Safe Medication Practices
Authors: Rajasekaran Senthil Kumar , Smith Julia , Engwall Keith 
Published: June 2021

With the growing emphasis on evidence‐based medicine, medical students face the challenge of assimilating a huge volume of new information during medical school. Among the most significant trends in medical education is the emergence of high quality medical applications for smart phones and tablets. As digital natives, millennial medical students respond well to this approach.First year medical students were chosen for this activity. We chose three apps (Micromedex, Epocrates and DynaMed) and for each app, the students were assigned questions related to a clinical case and a corresponding app to answer them. The tasks included a drug interaction check, adverse effect check, cost effective alternative check and patient advice and reference the levels of evidence (I, II and III). Also, students were directed to use the apps to perform similar tasks with the prescription drugs that their family or friends were taking. The students were asked to fill out an optional online pre‐ and post‐session survey rating their level of awareness and expertise in using these apps. Out of 75 students, 42 answered both surveys.Preliminary results indicate that self‐described ratings of application expertise rose substantially, as did their knowledge about critical clinical information relevant to prescribing practices. Students' knowledge of these applications also impacted their understanding of drug indications, efficacy, reactions, and interactions. Our results suggest that pedagogical interventions like these may hold potential to improve safe medication practices in clinical settings.
Mechanism and Regulation of GPCR Endocytosis in vivo using Rhodopsin as a Model
Authors: Sun Wesley , Ferng Darwin , Shieh Bih‐Hwa 
Published: June 2021

We explored the mechanisms and regulation of rhodopsin endocytosis in Drosophila by examining the trafficking itineraries of the major rhodopsin (Rh1) in vivo using transgenic flies expressing a modified Rh1 containing a C‐terminal mCherry tag (Rh1‐mCherry). By fluorescence microscopy, Rh1‐mCherry was detected in the visual organelles (rhabdomeres) of photoreceptors. Upon continued light stimulation, Rh1‐mCherry display light‐dependent endocytosis, and becomes enriched in the cytoplasm of photoreceptors. Internalization of rhodopsin may be mediated by the clathrin‐mediated endocytosis (CME). CME requires the presence of a minor phospholipid, phosphoinositol‐4, 5‐bisphosphate (PIP2) in the membrane. Interestingly, perturbation of the PIP2 biosynthesis fails to prevent the endocytosis of Rh1‐mCherry in rdgA mutants. The rdgA gene encodes diacylglycerol kinase critical for the recycling of PIP2.We also explored the contribution of two visual arrestins, Arr1 and Arr2, as adaptor proteins in promoting the endocytosis of Rh1. We introduced Rh1‐mCherry into either arr1 or arr2 mutant background and investigated how trafficking is affected. We show that internalization of Rh1‐mCherry is drastically reduced in the arr2 mutant. Arr2 is expressed 7fold more abundant than Arr1. Based on the finding, we conclude that Arr2 is critical for orchestrating the light‐dependent endocytosis of Rh1‐mCherry. Importantly, this Arr2‐mediated event does not appear to belong to the classical CME as it is insensitive to a reduction of PIP2 in the membrane.