bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardio‐Pulmonary Coupling II: Reduced Stroke Volume Effects on Time Phase Signals′ Combination at Integrative Site in CNS
Authors: Sun Xingguo 
Published: June 2021

INTRODUCTIONSince 2011 physiology conference, we introduced a New dynamic theory of breathing control: a complex model integrates multi‐systems. Another abstract described reduced left ventricle ejection fraction (EF) decrease the amplitude of arterial O2, CO2 and [H+] oscillations.HYPOTHESISWe assessed the hypothesis that except low EF, reduced Stroke Volume (SV) decrease the combined amplitude of arterial O2, CO2 and [H+] oscillations signals at integrative site due to different time courses blood arrive at chemical sensors.METHODSSmilar to another abstract; reduced SV, which results blood arrive at aorta and carotid body from different SV (time phase difference), was used to calculate the combined magnitudes of PO2 and PCO2 oscillation arrive at integrative site at CNS.RESULTSThe decreased SV (low CO) results the blood arrives at aorta and carotid by different SV, the weak combined signal (magnitude) for next breath at integrative site at CNS. This will results that mean of O2 and CO2 at central chemical sensors is unstable, and then breath control ¡°gain¡± goes up and down. Low SV may result periodic breathing pattern.CONCLUSIONSThe same O2 and CO2 oscillations, reduced SV will via low EF mixed chamber and decreased in combining signal for next breath at integrative site are influenced by different time phase. It is another explanation of Cardio‐Pulmonary Intra‐Coupling.
Galactooligosaccharides (GOS) decrease the probability of upper respiratory tract infection (URTI) in aged adults, but it is dependent on Mini‐Nutritional Assessment (MNA) score and the percentage of natural killer cells
Authors: Girard Stephanie-Anne , Nieves Carmelo , Downes Eric C , Christman Mary C , Mai Volker , Dahl Wendy J , Duriancik David M , Gardner Elizabeth M , Barkley Phillip L , Langkamp-Henken Bobbi 
Published: June 2021

Previously, we showed a reduction of URTI in academically stressed students with GOS. This study determined the effect of GOS on risk of URTI in aged adults over cold/flu season. In a randomized, double‐blinded study, adults (66±1 y) received 0 g (n=38) or 5 g (n=43) of GOS for 24 wk. Nutritional status was evaluated at baseline (wk 0) using the MNA (score <24 out of 30 is associated with risk of malnutrition). Blood was drawn at wks 0, 3 (concurrent with seasonal influenza vaccine administration) and 5 (2 wk post‐vaccination). PBMCs were stimulated in vitro with PHA, and IFNγ production was quantified. Subpopulations of CD45+ cells were determined. Wk 0 MNA scores (27±1) and %NK cells at all wks (15±1%, 14±1%, 15±1%) were not different between groups; however, both interacted with the intervention on probability of URTI. As MNA score increased, probability of URTI decreased, and this effect was greater with GOS vs. placebo. As %NK cells increased, the probability of URTI decreased with GOS and slightly increased with placebo. Percent change in IFNγ between wk 0 and wks 3 (−26±5 vs 13±19, P=0.053) and 5 (−17±8 vs 35±27, P=0.07) differed for placebo vs GOS, respectively. GOS had a greater effect than placebo on decreasing the probability of URTI with improving nutritional status, and unlike placebo, GOS decreased the probability with increasing %NK cells. This effect may be via alterations in IFNγ.Grant Funding Source: Corn Products International
Sympathetic inhibition attenuates hypoxia induced insulin resistance
Authors: Peltonen Garrett Lee , Scalzo Rebecca L , Schweder Melani M , Szallar Steve E , Binns Scott E , Wood Lacey M , Klochak Anna L , Schroeder Thies , Irwin David C , Hamilton Karyn L , Bell Christopher 
Published: June 2021

Acute exposure to hypoxia decreases insulin sensitivity in healthy humans. The mechanism is unclear but increased activation of the sympathetic nervous system (SNS) may be involved. We hypothesized that SNS inhibition would attenuate hypoxia induced insulin resistance. Insulin sensitivity (hyperinsulinemic euglycemic clamp) was determined in 10 men (23±1 years, body mass index 24.2±0.8 kg/m2 (mean±SE)) during normoxia (FIO2=0.21), hypoxia (FIO2=0.11), normoxia and SNS inhibition (48‐hour transdermal clonidine), and hypoxia and SNS inhibition. Oxyhemoglobin saturation was decreased (P<0.01) in hypoxia (63±2%) compared with normoxia (96±0%), and was unaffected by SNS inhibition (P>0.25). The area under the norepinephrine curve (relative to the normoxia response) was increased in hypoxia (137±13%; P=0.02); clonidine prevented the hypoxia induced increase under the norepinephrine curve (94±14%; P=0.43). Compared with normoxia (225±23 nmol/kg fat free mass/pmol/L/min) the glucose infusion rate (adjusted for fat free mass and circulating insulin), required to maintain blood glucose at 5 mmol/Lduring administration of insulin, was decreased in hypoxia (128±30; P=0.03), and unchanged during normoxia and SNS inhibition (219±19; P=0.86), and hypoxia and SNS inhibition (169±23; P=0.23). We conclude that short‐term SNS inhibition attenuates hypoxia induced insulin resistance.Support: DARPA N66001‐10‐c‐2134
Prolyl Hydroxylase Inhibition Attenuates Mast Cell Degranulation During Systemic Hypoxia Via Upregulation of Heme Oxygenase‐1
Authors: Wood John G. , Moncure Michael , Thomas James H. , Holloway Naomi B. , Gonzalez Norberto C. 
Published: June 2021

Acute systemic hypoxia (Hx) causes mast cell degranulation and increased leukocyte adherence in post‐capillary venules of rats. When animals are chronically hypoxic, microvascular inflammation resolves in part due to upregulation of heme oxygenase‐1 (HO‐1), which prevents mast cell activation. Inhibition of prolyl hydroxylase (PHD) increases hypoxia‐inducible factor‐1 (HIF‐1) levels, which promotes HO‐1 expression.ObjectiveOur goal was to evaluate whether inhibition of PHD attenuated Hx‐induced mast cell degranulation, and if upregulation of HO‐1 was involved.MethodsIntravital microscopy was used to measure mast cell degranulation and leukocyte adherence in mesenteric venules of anesthetized rats. The PHD inhibitor ethyl dihydroxybenzoate (EDHB) was injected s.c. to rats 24 hrs prior to experiments. Hx was produced in rats breathing 10% O2.ResultsHx caused mast cell degranulation and increased leukocyte adherence in the mesenteric microcirculation of vehicle‐ but not EDHB‐treated rats. Superfusion of the mesentery with the HO‐1 inhibitor zinc protoporphyrin caused a significant increase in mast cell degranulation and leukocyte adherence during Hx in EDHB‐ but not in vehicle‐treated rats.ConclusionInhibition of PHD reduces Hx‐induced mast cell degranulation and leukocyte adherence in part through HO‐1 upregulation, which is consistent with a HIF‐1‐dependent mechanism.
Blood‐Brain Barrier Na/HCO3 Cotransporters: Evidence for a Role in Ischemia‐induced Brain Na Uptake
Authors: Yuen Natalie Yuk-yee , Chen Yi-Je , Boron Walter F. , Praetorius Jeppe , Anderson Steven E. , OˈDonnell Martha E. 
Published: June 2021

Increased Na transport across the blood‐brain barrier (BBB) contributes to brain edema during the early hours of ischemic stroke. Our previous studies show that BBB Na‐K‐Cl cotransporter and Na/H exchange are stimulated by ischemic factors and inhibition of these Na transporters by bumetanide and HOE642, respectively, greatly attenuates Na uptake and edema in the rat middle cerebral artery occlusion (MCAO) model of stroke. In the present study, we examined the possibility that one or more Na/HCO3 cotransporters (NBCs) are present at the BBB and contribute to ischemia‐induced brain edema. NBC protein expression and activity were evaluated using Western blot and microspectroflurometric assays, respectively. We found the expression of NBCe1C and NBCn1 in bovine cerebral microvascular endothelial cells (CMEC) and freshly isolated rat brain microvessels. We also observed a Na‐ and HCO3‐dependent, HOE642‐insensitive H+ flux in CMEC that is comprised of both DIDS‐sensitive and DIDS‐insensitive components, indicating the presence of both NBCe1 and NBCn1 activity in the cells. Finally, localized 23Na MR spectroscopy was used to assess brain Na uptake in rats subjected to MCAO. We found that MCAO‐induced Na uptake was significantly reduced by DIDS (40 mg/kg, iv). These findings support the hypothesis that BBB NBCe1C and/or NBCn1 participate in ischemia‐induced brain Na uptake and edema formation.Supported by NINDS
Differential stimulation of duodenal HCO3− secretion by luminal fatty acids
Authors: Akiba Yasutada , Inoue Takuya , Higashiyama Masaaki , Rudenkyy Sergiv , Iwamoto Ken-ichi , Kuwahara Atsukazu , Kaunitz Jonathan D 
Published: June 2021

Luminal nutrients enhance mucosal defenses via gut hormone release. We examined the effects of long‐chain (LCFA) or short‐chain fatty acid (SCFA) receptor agonists on duodenal HCO3− secretion (DBS). We measured DBS with pH and CO2 electrodes in a perfused duodenal loop in anesthetized rats. Acetate or propionate, GPR43 agonist phenylacetamide 1 (PA1) or GPR40 agonist GW9508 was luminally perfused +/− iv dipeptidyl peptidase 4 inhibitor NVP728 or hormone receptor antagonist. LCFA receptor GPR40 and SCFA receptors GPR41/43 were expressed in the duodenal enteroendocrine cells. Luminal perfusion of acetate or propionate similarly increased DBS, enhanced by NVP728, while increasing GLP‐2 release in portal blood. Acetate‐induced DBS was reduced by the monocarboxylate transporter inhibitor, suggesting the acetate absorption‐mediated and GLP‐2‐mediated DBS. PA1 dose‐dependently increased DBS, unaffected by NVP728 or CCK‐A receptor antagonist, but inhibited by atropine or 5‐HT4 antagonist. The GPR40 agonist GW9508 increased DBS with GLP‐2 release, enhanced by NVP728. Activation of GPR40 by LCFA and possibly GPR41 by SCFA increases DBS via GLP‐2 release, whereas GPR43 activation stimulates DBS via muscarinic and 5‐HT4 receptor activation. The presence of fatty acid sensing in the duodenal mucosal defenses may be implicated in the pathogenesis of functional dyspepsia syndromes.VA Merit Review, R01 DK54221
Biotinylation of K16 in histone H4 causes chromatin condensation
Authors: Singh Mahendra P , Zempleni Janos 
Published: June 2021

Histone modifications play crucial roles in the control of gene activity, nuclear architecture, and genomic stability. Nucleosomes are the basic units of chromatin in eukaryotes, consisting of an octamer of histone core proteins wrapped by ~147 bp of DNA. Biotinylation of lysines (K) in histones H3 and H4 by holocarboxylase synthetase (HLCS) is a rare epigenetic repression mark, e.g., H4K16bio. Here, we tested the hypothesis that H4K16bio contributes toward chromatin condensation and, therefore, gene repression. We generated mutant recombinant histone H4 in which K16 has been replaced with cysteine (H4K16C) for subsequent chemical biotinylation with a thiol reactive reagent (H4K16Cbio). Nucleosomes were assembled by salt dialysis, using recombinant histones and the Widom 601 DNA sequence. DNA binding was analyzed by atomic force microscopy. Core octamers containing H4K16Cbio bound ~29% more DNA compared with octamers containing H4K16 or H4K16C (controls), suggesting biotin‐dependent condensation of chromatin. We conclude that biotinylation of H4 increases the nucleosomal affinity for DNA. We propose that histone biotinylation contributes to gene repression, in addition to the emerging role of HLCS as a member of a multiprotein gene repression complex in human chromatin.Grant Funding Source: ARD, and NIH DK063945, DK077816, and DK082476.
Establishment and characterization of novel in vitro models of gastric chief cell and metaplastic lineages
Authors: Weis Victoria G. , Petersen Christine P. , Nam Ki Taek , Whitehead Robert H , Goldenring James R 
Published: June 2021

Investigations of preneoplastic metaplasias in the stomach are limited by the lack of cell models for mature mucosal cells and metaplasias. We developed in vitro models of chief cells and spasmolytic polypeptide‐expressing metaplasia (SPEM) cells to study the transdifferentiation of chief cells into SPEM. Utilizing the Immortomouse, which is completely transgenic for tempertature‐dependent TAg, chief cells were isolated and cultured from untreated mice. SPEM cells were isolated from mice treated with L635, an acute SPEM induction model. mRNA and protein expression profiles were used to characterize the cultures. ImChief cultures express most chief cell markers with immunostaining for pepsinogen and Rab3D‐containing granules. After 2 weeks at 39°C, ImChief cells cease proliferating and resemble a more differentiated state similar to in vivo chief cells. ImSPEM cells express the SPEM markers TFF2 and HE4 and produce HE4‐containing granules. They lack expression of most other lineage specific markers. ImSPEM cells retain their proliferative ability for at least 1 month at 39°C, resembling the in vivo properties of SPEM cells. Our results indicate that the expression and proliferation profiles of the novel ImChief and ImSPEM cultures resemble in vivo chief and SPEM cell lineages. These cultures provide the first in vitro system for studying the molecular mechanisms of the metaplastic transition in the stomach.Department of Veterans Affairs Merit Review Award and NIH RO1 DK071590
Hyperhomocysteinemia decreases intestinal motility leading to constipation
Authors: Givvimani Srikanth , Munjal Charu , Narayanan Nithya , Tyagi Geetansh , Metreveli Naira , Tyagi Suresh 
Published: June 2021

Elevated levels of plasma homocysteine (Hcy) known as hyperhomocysteinemia (HHcy), has been implicated in inflammation and remodeling of intestinal vasculature and it also aggravates the pathogenesis of inflammatory bowel disease (IBD). Interestingly, colon is the pivotal site that regulates Hcy levels in the plasma. We hypothesize that hyperhomocysteinemia decreases intestinal motility through MMP‐9 induced intestinal remodeling leading to constipation.MethodTo verify this hypothesis we used C57BL/6J or wild type (WT), CBS+/−, MMP‐9 −/− and MMP‐9−/− + Hcy mice. Intestinal motility was assessed by barium meal studies and daily feces output. Expression of ICAM‐1, iNOS, MMP‐9 and TIMPs were studied by western blot and immunohistochemistry.ResultsBarium meal studies suggest that intestinal motility is significantly decreased in CBS−/+ mice compared to other groups. Fecal output to body weight ratio was significantly reduced in CBS−/+ mice compared to other groups. There was significant up‐regulation of MMP‐9, iNOS, and ICAM‐1 expression in the colon from CBS−/+ mice compared to WT mice.ConclusionsResults suggest that HHcy decreases intestinal motility due to MMP‐9 induced intestinal remodeling leading to constipation.
Dietary behaviors and acculturation in South Asian college students
Authors: Jasti Sunitha , Sachmechi Amanda 
Published: June 2021

ObjectiveTo determine whether the degree of acculturation is associated with dietary behaviors and body mass index (BMI) in first‐generation South Asian college students.MethodA cross‐sectional online survey assessed acculturation level, dietary behaviors, and BMI of 204 South Asian students at Queens College.ResultsMean age was 21 y (2.9) and mean BMI was 22.7 (4.1). Mean (SD) acculturation was 3.57 (0.62) on a scale of 1–5, 61% of the sample preferred South Asian food at home, while 30% preferred it at restaurants. The degree of acculturation was not significantly associated with BMI or dietary behaviors assessed in this sample. There was, however, a high prevalence of obesogenic dietary behaviors. Fast food was consumed at least 3 times a week by 40% of the students. Sweetened beverages were consumed by 53% and fried snacks by 50% at least 4–6 times a week; fats (butter, ghee, cream) were added to food at the table at least sometimes by 56%; and only a third (34%) of the participants always chose low fat type for dairy products. Furthermore, a majority of the students (64%) indicated that there are too many nutrition recommendations making it hard to know what to believe and 33% did not know which menu items in a restaurant have more/less fat.ConclusionAll South Asian college students may benefit from nutrition education regardless of the acculturation level.
Association between dietary protein and energy intake, handgrip strength (HGS), and lean body mass (LBM) in hypoalbuminemic maintenance hemodialysis (MHD) patients
Authors: Parsons Tara Rae , Bross Rachelle , Molnar Miklos Z , Kalantar-Zadeh Kamyar 
Published: June 2021

BACKGOUNDProtein energy wasting/malnutrition is a significant problem in MHD patients. More LBM and greater HGS are associated with better survival rates in MHD patients. These associations are not well described in hypoalbuminemic MHD patients who have increased morbidity and mortality.METHODSHypoalbuminemic (albumin <4.0 g/dL) MHD patients from DaVita Dialysis Centers in Los Angeles were enrolled in a randomized, controlled study (FREDI) associating meals during dialysis, phosphorus control and nutritional status. A dietitian measured HGS, assessed LBM by dual‐energy x‐ray absorptiometry, and protein and energy intake by interview‐assisted three‐day food record.RESULTSThe baseline association between protein and energy intake, HGS, and LBM was assessed in 65 (28 male, 37 female) MHD patients, including 33 Hispanics and 32 Non‐Hispanics with a mean (± SD) age of 56 (±13) years.

Body Mass (kg)
LBM (%)
Seum Albumin (g/dL)
HGS‐right hand (kg)
Protein Intake (g/day)
Energy Intake (kcal/day)

75.4 (±16.6)
68.9 (±8.5)
3.71 (±.27)
24.0 (± 8.7)
73.5 (± 31.3)
1573 (± 705)

Protein intake (r=0.38, p=.002), energy intake (r=0.45, p<.001) and HGS (r=0.43, p<.001) were positively correlated with percent LBM.

CONCLUSIONSThese findings suggest that even in hypoalbuminemic MHD patients, protein and energy intake is associated with better nutritional status assessed by HGS and LBM.Shire US Inc., Wayne, PA 19087.
Revamping anatomy education: student‐authored dissection manual significantly improves learning and academic performance
Authors: Tetzl Dustin , Neira Justin , Ramirez Jose , Grossmann Lily , Bernd Paulette 
Published: June 2021

In an effort to improve the first‐year medical students’ anatomy lab experience, we as second‐year students created our own custom dissection manual. Working with the course director, we tailored this dissector to Columbia University's anatomy course with marked advantages over commercial dissectors.Many factors make our dissector unique: step‐by‐step photographs of a cadaver dissection and supplementing diagrams, review checklists, concise instructions, dissection tips, and information only pertinent to structure identification. The dissector's efficacy was evaluated by comparison of student surveys, faculty assessments, and exam statistics from the 2010 and 2011 classes, who used the commercial or custom dissector, respectively.Comparison of 2010 and 2011 surveys showed an overwhelming increase in satisfaction with the new dissector, increased learning ease, more efficient use of lab time, and decreased frustration. Faculty reported an overall “higher dissection quality” and “less dependence on faculty” in the lab. Exam means increased by at least one standard deviation (N = 236, p < 0.0001).Due to its unique student‐developed nature, this project has closely addressed students’ needs, and has proven itself highly effective in its implementation at Columbia University. This student‐led model can serve as a template for other schools looking to customize and improve their anatomy curriculum.Grant Funding Source: none
Quercetin Bioavailability And Biotransformation Are Inversely Related To Vitamin C Status In College‐Aged Adults
Authors: Guo Yi , Mah Eunice , Jalili Thunder , Bruno Richard S 
Published: June 2021

Dietary quercetin (Q) may reduce the risk of cardiovascular disease (CVD), but little is known about its bioavailability. We conducted a pharmacokinetics study to define whether antioxidant status affects Q bioavailability in young adults. Participants (n = 8M/5F) ingested 1095 mg Q aglycone with a standardized meal. Then, plasma antioxidants [ascorbic acid (AA), tocopherols, uric acid, carotenoids], Q and its methylated metabolites isorhamnetin (I) and tamarixetin (T) were measured at timed intervals for 24 h. Q bioavailability (AUC0‐24 h 308–1738 μM x min) and maximum concentrations (Cmax 0.4–2.8 μM) exhibited high inter‐subject variability. AUC0‐24 h and Cmax of I and T were also highly variable (120–750 and 33–787 μM x min; 0.1–0.9 and 0.1–1.2 μM, respectively). AA, but no other antioxidants, was inversely related to Q AUC0‐24 h and Q Cmax (P<0.05; r = −0.63 to −0.49). AA was also negatively related to AUC0‐24 h of I + T (P<0.05, r = −0.58) and tended to inversely relate to Cmax of I + T (P=0.06; r = −0.46), suggesting that low AA status increases Q bioavailability and biotransformation. AA was also inversely related to myeloperoxidase (P<0.05, r = −0.56), a proinflammatory enzyme that increases CVD risk. These data suggest that low AA status increases Q bioavailability, possibly through a proinflammatory mechanism that increases its intestinal absorption.Grant Funding Source : Donaghue Nutrition Research Program
Dose response bioavailability of coffee chlorogenic acids in humans
Authors: Renouf Mathieu , Marmet Cynthia , Giuffrida Francesca , Williamson Gary , Dionisi Fabiola 
Published: June 2021

Chlorogenic acids are coffee bioactives that are becoming of great interest for their health promoting effects. However, human bioavailability of these compounds is not fully understood. We investigated dose response plasma appearance of coffee chlorogenic (CGAs) and phenolic (PAs) acids after ingestion of increasing doses of soluble coffee by 10 healthy volunteers.Two groups of metabolites appeared over 24h where plasma CGAs and PAs were measured after enzymatic treatment. The first group of metabolites appeared rapidly, less than 2 hours after ingestion, indicative of intestinal absorption. Dihydrocaffeic and dihydroferulic acids peaked around 10h, which suggest colonic metabolism and absorption. Regardless of the dose, colonic metabolites were the most present compounds, followed by phenolic acids and chlorogenic acids. Finally, all compounds quantified in plasma showed a positive dose response effect proportional to the ingested dose, indicating passive absorption mechanisms. It also highlights the importance of this beverage as a significant dietary source of bioavailable bioactive compounds.
Bioaccessibility of pistachio polyphenols, carotenoids and tocopherols in the upper gastrointestinal tract
Authors: Mandalari Giuseppina , Bisignano Carlo , Filocamo Angela , Chessa Simona , Saro’ Mariagiovanna , Torre Germana , Faulks Richard , Dugo Paola 
Published: June 2021

A number of studies have demonstrated positive effects of pistachio consumption in modifying lipid risk factors for coronary heart disease. The aim of the present study was to characterize pistachio polyphenols, carotenoids and tocopherols and investigate their bioaccessibility during digestion. A dynamic gastric model of digestion which provides a realistic and predictive simulation of the physical and chemical processing and accurately mimics both the transit time and the luminal environment within the human stomach was used for the digestion studies. Raw, roasted salted pistachios and muffins made with raw pistachios were tested. Results showed that pistachio polyphenols (59–63 mg/100 g), carotenoids (lutein 11–16 mg/100 g) and tocopherols (227–236 mg/100 g) are bioaccessible during digestion and therefore available for absorption in the gastrointestinal tract. No significant differences in bioaccessibility were observed between raw and roasted pistachios in the stomach and small intestine.However, the presence of muffin limited the release of protocatechuic acid and luteolin in the gastric and duodenal compartment. Polyphenols, carotenoid and tocopherol absorption would contribute to the beneficial relationship between pistachio consumption and health‐related outcomes.This work has been funded by the American Pistachio Growers.