bluuebunny/crossref_metadata_2025_split huggingface dataset:
Augmented supraorbital skin sympathetic nerve activity responses to symptom trigger events in rosacea patients
Authors: Wilson Thad E. , Toma Kumika , Metzler-Wilson Kristen , Sammons Dawn 
Published: June 2021

To investigate if rosacea alters skin sympathetic nerve activity (SSNA) and end‐organ responses, 12 patients and age‐ and sex‐matched controls underwent 2 symptom triggering stressors (mental and physical stress). Subjects performed 2‐min mental arithmetic and 2‐min isometric handgrip (35% of maximal voluntary contraction). SSNA (supraorbital microneurography), forehead skin blood flow (laser‐Doppler flowmetry), and forehead sweat rate (capacitance hygrometry) were measured. Heart rate and mean arterial pressure (MAP) were recorded via finger photoplethysmography. Cutaneous vascular conductance (CVC) was calculated by flux/MAP, and SSNA was normalized to baseline. Heart rate and MAP changes from baseline were not different between patients and controls during either stressor. Rosacea patients showed higher baseline sweat rate than controls (0.20±0.02 vs. 0.10±0.02 mg/cm2/min, p>0.05), and CVC trended higher compared to controls. SSNA during mental stress was higher in patients compared to controls (39±12% vs. 9±3%, p>0.05); similar augmented SSNA responses were observed during handgrip (rosacea = 31±13% and controls = 2±1%, p>0.05). These data identify trigger induced hyper‐responsiveness of sympathetic outflow in the face of rosacea patients and thus may be part of the etiology of the disease.Funded by a grant from the National Rosacea Society.
Hydrochlorothiazide exacerbates metabolic syndrome in the SHROB rat model
Authors: Ernsberger Paul , Agarwal Akshita , Lute Beth , Koletsky Richard J 
Published: June 2021

Metabolic syndrome consists of hypertension, insulin resistance, dyslipidemia and fatty liver. Thiazides are the leading treatment for hypertension, but some clinical studies have suggested adverse metabolic effects. We sought for the first time to characterize the metabolic effects of thiazides in an animal model of metabolic syndrome. SHROB rats are obese, hypertensive and express every component of human metabolic syndrome. Adult female SHROB rats (N=6 per group) were fed a purified diet (AIN 93) replete with electrolytes and treated in their drinking water for 5 weeks with either vehicle (250 ppm saccharine and 100 ppm sodium benzoate) or hydrochlorothiazide (achieved dose of 44±2 mg/kg/d). Systolic blood pressure fell progressively from 184±5 to 142±2 mmHg with thiazide treatment while remaining unchanged in controls. Heart rate was not affected. Body weight, food intake, and water intake did not differ between groups, nor did fasting glucose or insulin. Oral glucose tolerance testing (6 g/kg by gavage after an 18h fast) showed increased plasma glucose levels in the thiazide group (at 60 min post load, 394±48 vs 214±51 mg/dL in controls, P<0.05 by t‐test). Insulin levels at the same time were half again higher in SHROB treated with thiazide (90±20 vs 61±14 ng/mL in controls, NS, but two‐way ANOVA shows a difference, P<0.05 by F‐test). Relative liver mass was increased in the thiazide group relative to controls (43±3 vs 35±3 g/kg body weight, P<0.05 by t‐test). Thus, thiazide was an effective antihypertensive therapy in the SHROB model of metabolic syndrome but worsened glucose tolerance and insulin resistance and enlarged the already fatty liver. The secretory response of the pancreas to glucose was apparently not impaired or even increased, suggesting that insulin signaling may be affected by thiazides.Research support for this study was given by Ophthalmology Education Worldwide
Mechanisms of Skeletal Muscle Contraction‐Induced Rapid Vasodilation in Humans: Role of Vascular Hyperpolarization
Authors: Kirby Brett S , Crecelius Anne R , Richards Jennifer C , Garcia Leora J , Luckasen Gary J , Larson Dennis G , Dinenno Frank A 
Published: June 2021

A monophasic increase in skeletal muscle blood flow is observed following a brief single forearm contraction in humans. Evidence in dogs indicates an obligatory role of vasodilation via smooth muscle hyperpolarization, and recent in situ data suggest that activation of Na+/K+ATPase and KIR channels during muscle contraction contributes to this vasodilation. We tested the hypothesis that inhibition of Na+/K+ATPase and KIR channels via intra‐arterial infusion of ouabain and barium chloride (BaCl2), respectively, and thus vascular hyperpolarization decreases contraction‐induced rapid vasodilation in the human forearm. We measured forearm blood flow (Doppler ultrasound) and calculated vascular conductance 10s prior to, and for 30s after a single 1‐s dynamic forearm contraction at 10, 20, and 40% maximum voluntary contraction (MVC) in 12 young adults. Inhibition of hyperpolarization reduced total forearm vasodilation by ~74, 62, and 55% (10, 20, and 40% MVC, respectively). Additional blockade of nitric oxide synthase and cyclooxygenase further attenuated the response to a total reduction of ~80% for all intensities. The present study demonstrates a significant contribution of vascular hyperpolarization to contraction‐induced rapid vasodilation, and that collective blockade of nitric oxide, prostaglandins, and vascular hyperpolarization nearly abolishes this phenomenon in humans.HL102720
The use of gaze tracking to quantify learning
Authors: Zumwalt Ann C , Wice Mitchell , Bergethon Peter 
Published: June 2021

The long‐term goal of this ongoing study is to quantify how individuals of varying levels of expertise interact with visual data, to ultimately establish an objective assessment of expertise and learning. The current study investigates how gaze patterns shift as an individual becomes more familiar with an image. Specifically, this study tests the hypothesis that as an individual sees an image repeatedly they will examine the image for less time, and will fixate on fewer locations on the image for relatively longer durations of time. Subjects (n=13) were shown a random series of 100 images in which four images were repeated ten times and the rest of the images were seen once. Subjects were instructed to freely examine each image and advance to the next at any time, and their gaze patterns were recorded as they viewed the images. Outcome variables were the duration of time the subject viewed an image, number of gaze fixations, and the durations of those fixations. When the data were pooled the variation in each variable was too extensive to reveal clear trends from the first through tenth viewing, indicating the need for a larger sample size. However, the study did reveal that some individuals behaved as predicted, whereas others did the opposite: with each repeated view of an image, they investigated it for more time. While the sample size was inadequate to confidently quantify these possible trends, follow‐up studies are ongoing.Grant Funding Source: n/a
Feeding Soy Protein Isolate Prevents Impairment of Bone Acquisition by Western Diets as a Result of Insulin Signaling in Bone
Authors: Zhang Jian , Lazarenko Oxana P. , Badger Thomas M. , Ronis Martin J.J , Chen Jin-Ran 
Published: June 2021

Excessive consumption of high fat/high cholesterol “Western” diets during postnatal life results in increased energy intake, development of obesity and systemic insulin resistance. However, how this diet impairs bone development and remodeling is not well understood, and no effective dietary interventional strategy has emerged. In the current study, male rats pair‐fed a Western diet (WD) for 7 wks start from post natal day 20 displayed obesity with significantly increased gonadal and abdominal fat mass and body weight compared to control (p<0.05). WD rats had increased in bone marrow adiposity, insulin resistance and impaired glucose tolerance. Supplementation of soy protein isolates (SPI) ameliorated the effects of WD. Inhibition of WD‐induced impairment of bone acquisition by SPI was associated with increased undercarboxylated osteocalcin secretion and increased IRS1/Akt insulin signaling in osteoblasts. SPI normalized non‐esterified free fatty acid (NEFA) levels in WD rats. These results suggest that the effects of SPI diet on metabolism and body composition in WD rats are due to increased of secretion of active osteocalcin and stimulated insulin signaling in bone. Supported in part by ARS CRIS #6251‐51000‐005‐03S.Grant Funding Source: USDA / ARS CRIS
Dissemination of an Effective Weight Management Program for Mexican American Children in Schools
Authors: Palcic Jennette , Johnston1 Craig A , Breslin Whitney , El-Mubasher Abeer , Foreyt John P 
Published: June 2021

BaselineThe rates of child obesity are epidemic in the United States, and Mexican American children are at particular risk. We have found an intensive, multi‐component, school‐based, weight management intervention to be efficacious at reducing standardized body mass index (zBMI) in overweight children. Our next step was to examine the ability of PE teachers to implement this program (dissemination condition (DS)).ObjectiveThe current study sought to examine the efficacy of our intervention led by a PE teacher.MethodsStudents were randomized to either a research staff led intervention (SLI) or the DS condition. The SLI received classes 3 days a week. Students in the DS condition received the same curriculum but led by a PE teacher. Repeated measures ANOVA was used to evaluate weight changes using zBMI from baseline to 3, 6, and 12 months.ResultsStudents in both conditions significantly decreased their zBMI at 3, 6, and 12 months (F=50.7, p<.0001). Independently, both conditions demonstrated a significant decrease in zBMI at 3, 6, and 12 months (ILI: F=46.0, p<.001 and DS: F=12.8 p<.001). The SLI condition significantly out performed the DS condition (F=5.34, p<.01).ConclusionsOverall, the results suggest that our intensive school‐based weight management program can be disseminated. However, there does still appear to be an advantage to the intervention when implemented by health professionals.
A Survey of Memorial Ceremonies in United States Anatomy Programs
Authors: Jones Trahern W , Nwojo Macaulay , Pawlina Wojciech , Lachman Nirusha 
Published: June 2021

Anatomy programs that incorporate dissection of donated human tissue often hold ceremonies of gratitude and reflection for body donors. The content of these ceremonies often include learners’ reflections on mortality, respect, altruism, and personal growth told through various humanities modalities. The task of planning is usually faculty‐ and student‐led with participation from other health care students. Objective information on current memorial ceremonies for body donors in anatomy programs in the United States appears to be lacking. The number of programs in the United States that currently plan these ceremonies and information on trends in programs undertaking such remain unknown. Anatomy program directors throughout the United States were issued a brief, voluntary, thirteen‐item questionnaire on memorial ceremonies held at each institution. Qualitative data regarding the number of anatomy programs which hold their own memorial ceremonies, the content of such ceremonies, how they are planned, level of confidentiality maintained, and the types of participants who attend these events will be presented. This information may serve as a guide to institutions considering initiating a ceremony of their own.Grant Funding Source : Department of Anatomy
The Desmosomal Protein, PERP, is Required for the Pro‐ Inflammatory Response to Salmonella Typhimurium Infection
Authors: Hallstrom Kelly , Srikanth C. V. , Agbor Terence , Demma Zachary , McCormick Beth A 
Published: June 2021

Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of several Salmonella strains responsible for over 40,000 cases of Salmonella‐induced gastroenteritis in the United States yearly. Salmonella invade the apical surface of intestinal epithelial cells and trigger inflammation through the activity of type three secreted effectors. One such effector, SipA, activates signal transduction cascades that ultimately lead to the recruitment of neutrophils to the site of invasion. Previous studies showed that SipA acts extracellularly to induce neutrophil migration. Recent studies from our lab demonstrated that SipA requires processing by CASPASE‐3 to be fully functional, and that SipA induces release of activated CASPASE‐3 at the mucosal surface. In order to understand how SipA triggers these events without being translocated into the cell, we sought to identify an interacting host protein.We have determined that the desmosomal protein, PERP, is a binding partner of SipA. We have further observed that PERP accumulates at the apical surface during Salmonella infection in a SipA‐dependent manner, and that loss of PERP via siRNA knockdown results in decreased neutrophil migration during Salmonella infection. Additionally, we see reduced levels of activated CASPASE‐3 when PERP is knocked down. These results suggest PERP plays a crucial role in the pro‐inflammatory response to Salmonella infection.Funding Sources: NIH, NIDDK, Crohn's and Colitis Foundation of America
Kruppel‐like transcription factor KLF8 regulates of early adipocyte differentiation
Authors: Kim Hyo Jung , Choi Hyeonjin , Lee Yoo Jeong , Lee Hye-min , Yu Jung Hwan , Kim Jae-woo 
Published: June 2021

KLF8 is a zinc‐finger transcription factor known to play an essential role in cell cycle and differentiation. However, its physiological roles and functions in 3T3‐L1 cells remain relatively unclear. In the present study, we showed that KLF8 acts as a key regulator controlling adipocyte differentiation. In 3T3‐L1 preadipocytes, KLF8 expression was induced at an early stage of differentiation which was followed by expression of PPAR¥ã2 and C/EBP¥á. The mRNA level of KLF8 dramatically increased at 36 h and 48 h during differentiation and the protein level also gradually increased after 36 h. This induction and differentiation was attenuated significantly by the presence of small interfering RNA against KLF8, whereas overexpression of KLF8 induced 3T3‐L1 differentiation. Furthermore, overexpression of KLF8 induced PPAR¥ã2 and C/EBP¥á promoter activity and the direct binding site in C/EBP¥á promoter exists between (−205) and (−89) region. Taken together, this study provides KLF8 as a key component of the transcription factor network that controls the terminal differentiation during adipogenesis.This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011‐0030711 and 2011‐0015665) and by Korean Research WCU grant (R31‐2008‐000‐10086‐0) from the Korean Ministry of Education, Science, and Technology.
Association of apolipoprotein A5 gene ‐1131T>C polymorphism and metabolic syndrome in Korean subjects
Authors: Song Kwang Hoon , Yu Sung-Gon , Yu Hyunjoo , Kim Jong Yeol 
Published: June 2021

The apolipoprotein A5, APOA5, genetic polymorphisms, ‐ 1131T>C (rs662799) has been reported to be associated with hypertriglyceridemia that is one of the metabolic syndrome components. We assessed the association between the genetic polymorphism of APOA5 ‐1131T>C and lipid parameter and other risk factors of the metabolic syndrome in Korean subjects.A total of 2,683 participants from 20 oriental medical hospitals in Korea between 2006 and 2011 were enrolled. The APOA5 ‐ 1131T>C genotype was significantly associated with serum high‐density lipoprotein cholesterol levels (effect= −1.516 mg/dL, p = 6.414E‐06) in total study population after adjustment for differences in age and gender. The association of APOA5 ‐ 1131T>C with serum triglyceride was also significant in an additive genetic model (effect = 19.891 mg/dL, p = 3.876E‐17). Multiple logistic regression model adjusted for age and gender revealed that the subjects with CC genotype had an increased risk for metabolic syndrome (OR= 1.951, 95% CI=[1.443–2.637], P = 1.397E‐05).We demonstrated that APOA5 ‐1131T>C polymorphism was not only associated with serum high‐density lipoprotein cholesterol and triglyceride levels but also was associated with the metabolic syndrome as a result of its remarkable effect on serum triglyceride levels in Korean subjects in the current study.
Characterization of Lipid Droplet and Its Regulation by Caveolin‐1 in Endothelial Cells
Authors: Kuo Andrew , Zhang Xinbo , Harrison Kenneth D. , Sessa William C. 
Published: June 2021

Lipid Droplet (LD) is a unique organelle involved in many biological processes such as cellular energy homeostasis and lipid metabolism. One of the LD‐associated proteins reported is Caveolin‐1 (Cav‐1). Cav‐1 is a 21‐kDa integral membrane protein with a putative hairpin structure and localized in caveolae microdomains on the plasma membrane. Recent studies have shown that Cav‐1 can be redirected to the surface of LD, implying a novel function of Cav‐1.Endothelial cells (EC), as a key cell type segregating plasma lipids from tissue, are highly enriched in Cav‐1, suggesting the potential role of Cav‐1 in regulating LD homeostasis in EC. In this study, we first show that LDs are formed in EC at atheroma, indicating the potential physiological function of LD in EC. We next find that LD formation is significantly reduced in EC isolated from Cav‐1 null mice. Fatty acid uptake is not altered in Cav‐1 deficient EC, suggesting an intracellular regulation of LD by Cav‐1. We therefore measure LD formation and degradation separately in Cav‐1 deficient EC. Interestingly, activity of diacylglycerol acyltransferases is increased in Cav‐1 null EC while breakdown of triglyceride (TG) is not significantly changed. Taken together, our findings showed that LD can be observed in EC in vivo and its formation is regulated by Cav‐1 independently of fatty acid uptake and TG biosynthesis.
Breastmilk cells produce milk proteins in the culture dish
Authors: Hassiotou Foteini , Metzger Philipp , Trengove Naomi , Lai Ching Tat , Filgueira Luis , Hartmann Peter 
Published: June 2021

We have recently identified in human breastmilk early‐stage stem cells capable of multi‐lineage differentiation. To elucidate the potential of these cells to differentiate into functional lactocytes in vitro, freshly expressed breastmilk was collected, and cells shown by qPCR to express stem cell markers were cultured in mammary differentiation medium for up to four weeks. qPCR was then used to detect and quantify mRNA of milk proteins (lactoferrin, LF; α‐lactalbumin, LA) in cultured cells, whereas immunofluorescence microscopy was used to detect them at the protein level. Culture supernatants were harvested at regular time points and Western Blotting was used to examine expression of milk proteins and their glycosylation patterns. Plated breastmilk cells attached to the substrate and proliferated, forming epithelial colonies. Cells from the colonies gradually differentiated into functional lactocytes producing LF and LA, which were detected in harvested cultured cells both at the mRNA and protein levels. LF and LA were also secreted into the culture supernatants over the culture period of 4 weeks. Glycosylation of secreted milk proteins was observed at the molecular weights of LF and LA. It is concluded that breastmilk cells are able to differentiate in culture into functional lactocytes producing and secreting milk proteins, a number of which are glycosylated.Grant Funding Source : Women and Infants Research Foundation, Medela AG
Active transcription factors in the development of the small intestine during early life
Authors: Zhang Man , Liao Yalin , Lonnerdal Bo 
Published: June 2021

Transcription factors (TFs) regulate downstream gene expression individually or cooperatively in different cell types and specific tissues. Human milk contains several growth factors that maintain gastrointestinal mucosal homeostasis. We chose two major growth factors in human milk, TGF‐β and IGF‐1 to study global activation of TFs during early intestinal development in IEC‐6 (crypt cell) and FH74 cells (fetal intestine). TGF‐β treatment (10 ng/ml) for 5d significantly induced differentiation (expression of alkaline phosphatase) of IEC‐6 and lead to an abundance of cytoplasm and clear cell boundaries. Optimum proliferation of FHs 74 was found at 30 ng/ml IGF‐1 treatment for 24h (no significant change in morphology). Active transcription factors were detected by Protein‐DNA Array. For IEC‐6 cells, we found EGR1 and YY1 were upregulated; CREB, E2F1, Pax3 and OCT1 were downregulated. By bioinformatics analysis, we found 3 binding sites for EGR1 in the promoter of mir‐146b (−795/−786, −900/−812, −1013/−1005), which has been shown to be upregulated and play a role in TGF‐β signaling. In FHs 74 cells, c‐Myb was upregulated, whereas CREB, EGR1, P53 and Pax3 were downregulated. In conclusion, we showed several transcription factors are regulated by TGF‐β and IGF‐1 during small intestinal development. EGR1 was further found to participate in miRNA regulation of the TGF‐β treatment.Grant Funding Source : Mead Johnson Nutrition Global Discovery
Season, adiposity, and baseline 25‐hydroxyvitamin D are predictors of maternal change in vitamin D status from 1 to 4 months postpartum
Authors: Phan Anna , Gallo Sina , Vanstone Catherine , Agellon Sherry , Rodd Celia , Weiler Hope 
Published: June 2021

There is limited information on the vitamin D status of lactating women and the potential known predictors that contribute to vitamin D status during lactation. The objectives of this study were to determine vitamin D status of lactating women and identify key predictors of vitamin D status at 4 mo and change since 1 mo postpartum. Healthy, lactating mothers (n=44) in Montreal were recruited between May 2010 to April 2011. Fasted venous blood samples were collected at 1 and 4 mo postpartum for analyses of plasma 25‐hydroxyvitamin D (25(OH)D) by LIAISON® (Diasorin). Demographics, sun exposure, skin pigmentation, anthropometry, body composition, supplement use, and nutrition information were collected to identify predictors of 25(OH)D. From 1 to 4 mo postpartum, there was a significant decrease in 25(OH)D from 73.0 ± 21.6 nmol/L to 62.4 ± 18.3 nmol/L (p<0.001). At 1 mo, 7 (15.9%) mothers had 25(OH)D <50 nmol/L and 26 (59.1%) had 25(OH)D <75 nmol/L. At 4 mo, 9 (21.4%) mothers had 25(OH)D <50 nmol/L and 30 (71.4%) had 25(OH)D <75 nmol/L. Predictors of vitamin D status at 4 mo postpartum included weeks in the synthesizing period, vitamin D intake, and % change in body fat and predictors of change in 25(OH)D included baseline 25(OH)D, weeks in the synthesizing period, and % change in weight. These predictors are important to consider to prevent declines in vitamin D status during lactation.(Supported by CFDR).