bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex Specific Differences in the Predictive Value of Cholesterol Homeostasis Markers and 10‐Year CVD Event Rate in Framingham Offspring Study
Authors: Matthan Nirupa Rachel , Zhu Lei , Pencina Michael , D'Agostino Ralph B. , Schaefer Ernst J. , Lichtenstein Alice H. 
Published: June 2021

Data are inconsistent on factors influencing plasma cholesterol homeostasis marker levels and their value in predicting subsequent CVD events.We assessed the relationship between markers of cholesterol absorption (campesterol, sitosterol, cholestanol) and synthesis (squalene, desmosterol, lathosterol), and 10‐year CVD incidence in FOS participants without CVD at baseline and not taking lipid lowering medications (N=2616). The primary endpoint was “hard” coronary heart disease (HCHD: coronary death and myocardial infarction [MI]), and secondary endpoint was full CVD (HCHD + stroke, coronary insufficiency, angina pectoris, PAD and CHF). In cross‐sectional analysis, significant differences by sex, age, BMI, BP and smoking status were observed. In both women and men, lower cholesterol absorption was associated with higher triglyceride and lower HDL‐C levels, while lower cholesterol synthesis was associated with higher LDL‐C levels (p<0.05). In women only, lower cholesterol synthesis and absorption were associated with higher non‐HDL‐C levels. Using Cox proportional hazards model correcting for standard CVD risk factors, squalene levels were associated with lower HCHD in women (HR=0.70 [0.5–0.9]). In contrast, squalene (HR=1.40 [1.1–1.8]) levels were associated with higher HCHD in men (p‐value <0.0001 for interaction). The cholesterol absorption markers were not predictive of HCHD or full CVD in either sex.These data suggest significant sex differences in the 10‐year prognostic value of cholesterol synthesis markers and mortality as well as MI incidence.NIH‐HL‐074388, NO1‐HC‐25195 and USDA #: 58–1950–4–401
Pregnancy‐specific up‐regulation of zinc (Zn) absorption does not occur in indigenous Mayan population
Authors: Hambidge K Michael , Mazariegos Manolo , Westcott Jamie E , Miller Leland V , Close Kelly , Goco Norman , Kemp Jennifer F , Lei Sian , Krebs Nancy F 
Published: June 2021

Absorption of Zn has been reported to be up‐regulated in late pregnancy (Donangelo, Nutrients, 2012) which has implications for estimating the effect of pregnancy on Zn dietary requirements. The objective of this study was to undertake a longitudinal study of Zn absorption pre‐pregnancy, first and third trimester in 17 indigenous Guatemalan women who were participating in a low phytate maize study with maize as the principal dietary component. Fractional absorption of Zn (FAZ) was determined using extrinsic labeling with a dual isotope tracer ratio method; duplicate diets were analyzed to determine total daily Zn intake (TDZ); total absorbed Zn (TAZ, mg/d) calculated from FAZ × TDZ. As there was only one difference between low‐phytate and control groups for one variable at one time, data were subsequently combined and significance across time points determined. Phase differences (mean (SD)) are summarized in the table:For both FAZ and TAZ there was a significant difference across the 3 time points, attributable to the Δ between preconception and early pregnancy phase for both FAZ and TAZ. A Spearman correlation for TAZ in the 1st trimester phase showed that this was attributable to a lower TDZ. In conclusion, the results of this study did not support the concept of up‐regulation of Zn absorption specific to late pregnancy. Supported by Eunice Kennedy Shriver NICHD/NIH #HD04065.
Acute phase proteins are more elevated in acute respiratory infections than in diarrhea.
Authors: Contreras‐Manzano Alejandra , Villalpando Salvador , Lamadrid Héctor , Shamah‐Levy Teresa 
Published: June 2021

IntroductionDifferences in the responses in the secretion of lymphocytes and limphokynes by diarrhea and acute respiratory infections (ARI) predict differences in the secretion of c reactive protein (CRP) and alpha glycoprotein (AGP.)ObjectiveTo compare the magnitude of the acute inflammation as by CRP and AGP in a group of school age children suffering episodes of diarrhea or ARI (duration and symptoms)Material y methodsMorbidity data from the prior 14 d and final blood samples to measure CRP and AGP were obtained. The values of CRP, AGP and ferritin were log transformed. The evaluation of inflammation for diarrhea and ARI was made by linear regression models with random effects.ResultsOne episode of ARI produce greater CRP response than one of diarrhea (0.637, p=0.01) and two or more symptoms of ARI produced a greater CRP and AGP response than diarrhea (0.357 and 0.810, p<0.01, respectively). An increase of ferritin was seen in both infections when CRP and AGP were elevated (Ratios infection/no infection: 1.93 [1.68–2.22] and 1.84 [1.56–2.18], respectively, (p<0.001).ConclusionOur data demonstrate that ARI has a greater acute response as by CRP and AGP changes and by number of symptoms than diarrhea.
Dietary nucleotides and yeast extract affect the composition and metabolic activities of the swine gut microbiota in a new in vitro fermentation model
Authors: Doo Eun‐Hee , Chassard Christophe , Lacroix Christophe 
Published: June 2021

Nucleotides (NT) are important compounds to many biological processes but data on the exact role of NT on the gut microbiota remain unclear. In this work we investigated the effects of dietary NT in a medium formulated to simulate the pig ileal chyme on gut microbiota composition and activity using a novel continuous in vitro intestinal fermentation models mimicking the proximal colon. Pig fecal microbiota was immobilized in gellan‐xanthan beads and used as a continuous inoculum in a novel intestinal model platform, operated with multiple parallel reactors to compare treatments on the exact same microbiota composition. Daily effluent samples were collected and analyzed to investigate the composition (qPCR, pyrosequencing) and metabolic activities (HPLC) of the microbiota.We measured significant shifts of microbial diversity, microbiota composition, and activity of effluent samples induced by dietary NT and YE treatments. In particular Lactobacilli (+1.4 Log10) and propionate concentration (+18.7 %) significantly increased in 7.5 g/l high NTYE compare to the control medium. Our data suggest beneficial effects of dietary NT in YE on pig gut microbial balance, associated with enhanced propionate production which could reinforce the barrier effect of the gut microbiota and increased populations of beneficial microbes.This study was supported by a grant from the Worldwide Research Alltech, Inc. in USA.Grant Funding Source: Nutrition (ASN): ASN Graduate Student Research Award Competition, supported by the Nutritional Sciences Council
Pathophysiologic and metabolomic analyses in a model for closed abdomen septic swine treated with negative pressure therapy (NPT)
Authors: Norbury Kenneth Carl 
Published: June 2021

This study evaluated the impact of NPT in a porcine model of sepsis using pathophysiologic and metabolomic analyses. NPT consisted of polyurethane foam dressing with a visceral protective layer that extended into the paracolic gutters. NPT at −125 mmHg evacuated ascites into a canister. Injury was induced in 10 female swine via intestinal ischemia/reperfusion and induction of sepsis with a fecal suspension into the peritoneal cavity. After 10 hours, NPT was applied to 5 animals, and the abdomen closed, initiating treatment for up to 38 hours. Five control animals received no NPT. Animals were monitored throughout the study and terminal histopathology was performed. Biochemical and metabolomic analyses were performed on blood samples taken at intervals throughout the study. Inflammatory responses were measured by proteomic analysis of peritoneal and plasma samples. Findings are summarized below.

Organ System
Parameter
Control
NPT

I/R
Lactate
↑
↓

Hemodynamic
CVP
↑
↓

SvO2
↓
↑

Pulmonary
PaO2:FiO2 & Cstat
↓
↑

Acute alveolar congestion; interstitial edema and congestion
↓
↑

Renal
BUN & Creatinine
↑
↓

Inflammatory
TNF‐α
↑
↓

Metabolomic
myo‐inositol (a storage reservoir for proinflammatory arachidonic acid)
↑
↓

Long chain fatty acid biosynthesis
↓
↑

In this swine model of ischemic/reperfusion injury and sepsis, NPT had a beneficial effect on reversing the effects of injury compared to a control group that did not receive NPT.Study funded by KCI.
Evaluation of the VPT‐60 to measure peripheral nerve sensitivity
Authors: Gibson Janelle , Blackburn Mollie , Breen Paul , Latman N. S. 
Published: June 2021

The loss of peripheral nerve sensitivity can result in serious morbidity (including limb amputation) and mortality. Monitoring peripheral nerve sensitivity is important in avoiding these consequences.The purpose of this study was to evaluate the capability of an experimental VPT‐60 to accurately determine peripheral nerve sensitivity. Peripheral nerve sensitivity measurements from the VPT‐60 were compared to measurements of the two clinical reference standards, Semmes‐Weinstein monofilaments (SWM) and the Bio‐Thesiometer (BT).Peripheral nerve sensitivity and temperature of the index finger tip of 41 subjects, with ages ranging from 20–87 years, and mean SWM size range of 2.4–4.2 were measured. Finger tip temperature ranged from 71.4–88.2°F, and the force exerted by the finger on the vibrating probe ranged from <1.0 to 82 grams. Each subject's nerve sensitivity was measured 3 times with each of the 3 instruments.The correlation coefficient (r) of VPT‐60 and SWM was 0.75 and between the VPT‐60 and the BT was 0.86. The r between SWM and BT was only 0.51. As the nerve sensitivity decreased, the sensitivity of the VPT‐60 to detect changes increased. Reliability of the VPT‐60, SWM, and BT was 0.88, 0.78, and 0.74 respectively. In conclusion, this study indicates that the VPT‐60 provides results that are as capable as, if not more capable than, the gold standards in determining peripheral nerve sensitivity.
Evaluation of Ion Torrent's AmpliSeq Cancer Hotspot Panelv2 on FFPE tissues
Authors: Tunkey Christopher D. , Amos Christopher I. , Wells Wendy A. , Tsongalis Gregory J. 
Published: June 2021

ObjectiveWe routinely perform clinical molecular genetic testing using PCR‐based methods to detect BRAF, KRAS and EGFR variants in human cancers. Clinically actionable findings are reported to oncologists who can then personalize management strategies for any given patient. In this study we evaluated precision and accuracy of the Ion Torrent AmpliSeq Cancer Hotspot Panelv2 (46 genes).MethodsSix known mutation positive FFPE tissues were selected (2 BRAF, 2 KRAS, 2 EGFR mutants). Normal kidney and colon FFPE tissues were used as controls. 10ng of starting material from each sample was used to prepare 8 barcoded libraries. The libraries were multiplexed and run through on 3 separate OneTouch reactions and then processed on 3 separate 316 chips over a period of two weeks.ResultsThere was 100% concordance between previous PCR results and the corresponding variants identified in each of the mutant patient samples using the Ion Torrent panel. The BRAF, EGFR and KRAS mutations were consistently identified in each of the triplicate NGS reactions.ConclusionsSamples chosen based on a diversity of important clinical results were selected as a test set to evaluate the performance of the AmpliSeq Cancer Panel Hotspotv2. Every sample included in an Ion Torrent run with a known mutation status has been confirmed when run on the PGM. We also demonstrated the ability of this platform to produce consistent variant calls between runs and offer better coverage of clinically important gene regions.
Stretch‐sensitive microRNA expression and signaling events in vascular smooth muscle
Authors: Turczynska Karolina , Swärd Karl , Hellstrand Per , Albinsson Sebastian 
Published: June 2021

Vascular smooth muscle cells are constantly exposed to mechanical force by the blood pressure, which is thought to regulate smooth muscle growth, differentiation and contractile function. We have previously shown that expression of small non‐coding RNAs, microRNAs (miRNAs), is essential for regulation of smooth muscle phenotype including stretch‐dependent contractile differentiation.In this study we have investigated the effect of mechanical stretch on miRNA expression and the role of stretch‐sensitive miRNAs for intracellular signaling in smooth muscle.Mechanical stretch was applied to mouse portal veins in organ culture ex vivo by attaching a gold weight at one end of the vessel for 24h. MiScript whole genome miRNA PCR arrays analysis, comparing miRNA levels in stretched versus non‐stretched portal veins, revealed a dramatic decrease in the miR‐144/451 cluster level with no change in other active miRNA strands. Furthermore, we could confirm that these miRNAs target the AMPK signaling pathway, which correlates with an increased AMPK activation in stretched portal veins.In conclusion, our results suggest that reduced expression of miR‐144/451 in stretched portal veins could participate in the regulation of AMPK signaling. This effect may represent a negative feedback mechanism, limiting stretch‐induced growth in vascular smooth muscle.
The PreBötzinger Complex (preBC) Partially Mediates Opioid‐Induced Respiratory Depression in Young but not in Adult Rabbits
Authors: Stucke Astrid G , Zuperku Edward J , Prkic Ivana , Hopp Francis A , Stuth Eckehard AE 
Published: June 2021

It is yet unclear which brainstem areas are involved in respiratory depression by clinical doses of opioids. This study investigated whether the effects of the intravenous mu‐opioid agonist remifentanil could be reversed by local injection of naloxone (NAL) into the preBC and whether this reversal was different in young and adult animals.The study was approved by the local Animal Care Committee and conformed to NIH standards. 12 adult (3–4kg) and 15 young rabbits (13–23d, 110–550g) were anesthetized with 1–1.5 MAC sevoflurane, tracheotomized, ventilated and decerebrated. The location of the preBC was identified by neuronal recordings and the phrenic response to injection of D,L‐homocysteic acid. Remifentanil (0.08–0.5 mcg/kg/min) was infused intravenously until significant respiratory slowing and depression of peak phrenic activity (PPA) occurred. NAL (1mM, 70nl in young, 280nl in adults) was injected locally into the area of the preBC bilaterally. Local NAL partially reversed the depression of PPA (p=0.02) and the lengthening of expiratory time (p=0.01) in young but not in adult rabbits. Respiratory drive (PPA/inspiratory time) was unchanged. This is the first study to show that the preBC partially mediated the opioid‐induced changes in respiratory timing, though not in respiratory drive, in young rabbits but played no role in adult animals.Supported by FAER grant MRTG‐BS‐02/15/2010‐Stucke
Myocardial AT1 gene expression is increased in a model of left ventricular hypertrophy induced by high salt intake.
Authors: Pereira Rafael Canavel , Katayama Isis Akemi , Heimann Joel Claudio 
Published: June 2021

ObjectiveTo evaluate gene expression of the renin‐angiotensin system components in a model of left ventricular hypertrophy induced by high salt intake demonstrated in a previous study.MethodsWistar rats were fed normal (NS1.3% NaCl) or high (HS 8%) salt diet since weaning. From the 7th week of age, two HS subgroups received hydralazine or losartan (HZ 15 and LOS 20mg/kg/day). Angiotensinogen, renin, ACE, ACE2, AT1 and AT2 gene expression in left ventricle were measured.Results (n=8/group)

NS
HS
HS+HZ
HS+LOS

Angiotensinogen/GAPDH (IDV)
0.21±0.017a
0.19±0.017a
0.21±0.013a
0.19±0.024a

Renin/GAPDH (IDV)
0.71±0.02a
0.68±0.02a
0.67±0.02a
0.67±0.02a

ACE/GAPDH (IDV)
0.87±0.03a
0.83±0.05a
0.97±0.06a
097±0.05 a

ACE2/GAPDH (IDV)
0.41±0.02a
0.43±0.02a
0.37±0.03a
0.34±0.02a

AT1/GAPDH (IDV)
0.23±0.00a
0.46±0.06b
0.45±0.06b
0.22±0.00a

AT2/GAPDH (IDV)
0.52±0.04a
0.51±0.03a
0.45±0.03a
0.44±0.02a

Data are reported as mean±SEM. Means in row with superscripts without a common letter differ, P<0.05
ConclusionHigh salt intake increases AT1 gene expression, however it is prevented by losartan treatment. Supported by FAPESP and CNPq.
Fucosylated TLR‐4 signaling mediates microbial induction of intestinal fut2 expression
Authors: Nanthakumar Nanda N , Meng Di , Newburg David S. 
Published: June 2021

Toll‐like‐receptor (TLR) binding by specific microbial pattern‐recognition molecule leads to a cascade of innate immune response by activating NF‐κB and/or IRF‐dependent inflammatory signaling pathways. Bacterial‐colonization is also known to stimulate mucosal fucosylation in the gut without activating inflammatory responses, however, it is not known whether this non‐inflammatory response is mediated by a specific TLR. The goal of this study is to determine, if a specific TLR mediates colonization‐dependent intestinal fucosylation. Induction of high fucosylated phenotype of the mature gut occurs in the wildtype mice, but not in the TLR4−/− mice. In the absence of microbiota, a novel and previously unreported form of fucosylated‐TLR4 is generated in the colonocytes. A TLR4 specific ligand, LPS, or monocolonization by a gram‐negative bacterium, Bacteroides fragilis, is sufficient to induce intestinal fucosylation without activating inflammatory responses. This novel fucosylated TLR4 is also activated by a specific α1,2‐fucosylated epitope binding ligand, UEA1, that generated a signaling pathway that is non‐inflammatory and NF‐κB and IRF3 independent. The ERK and JNK‐dependent signaling by the gut microbiota by activating this novel fucosylated TLR4 result in transcriptional induction of the secretor (fucosyltransferase 2; fut2) gene in the epithelium that leads to elevation of fut2 mRNA and FucT II activity. The resultant mucosal fucosylation creates a niche that facilitates colonization by a distinct fucose‐utilizing microbiota and this type of interkingdom communication between the microbiome and the epithelium seems to be central to establishing a protective microbial ecosystem in the gut. This may help explain of a significant association between lack of secretor gene expression and intestinal inflammatory diseases such as necrotizing enterocolitis and Crohn's disease.Supported by HD013021, AI075563, and DK070260.
Sulforaphane protects small intestinal mucosa from indomethacin‐induced injury in mice via nrf2‐dependent mechanisms
Authors: Sato Junya , Yanaka Akinori 
Published: June 2021

BackgroundNSAIDs cause GI mucosal injury by generating reactive oxygen species. Sulforaphane (SFN), an isothiocyanate compound rich in broccoli sprouts, up‐regulates nrf2‐dependent antioxidant enzymes. We have previously shown that SFN up‐regulates hemoxygenase‐1 (HO‐1) expression in intestinal epithelial cells in vitro, and protects small intestine from indomethacin (IND)‐induced injury in vivo. In the present study, we examined if nrf2 plays a role in the protection by SFN from IND‐induced small intestinal injury using nrf2‐deficient mice in vivo.MethodsIND‐induced small intestinal injury was induced by injection of IND in nrf2+/+ and nrf2−/− C57/BL6 mice. Sulforaphane glucosinolate (SGS), a precursor of SFN, was orally administered before injection of IND. Mucosal injury was evaluated by lesion score, Evans blue exudation, myeloperoxidase activity, expression of TNF‐α and IL‐6. Mucosal invasion of anaerobic enterobacteria was quantitated by incubating the mucosa in Gifu anaerobic medium agar.Results1. IND caused small intestinal injury, effects demonstrated more in nrf2−/−, than in nrf2+/+ mice. 2. SGS attenuated the IND‐induced injury in nrf2+/+, but not in nrf2−/− mice. 3. SGS inhibited invasion of anaerobic bacteria into the mucosa in both types of mice.Conclusions1. Nrf2 contributes to protection of small intestinal mucosa from IND‐induced injury, 2. SFN affords protection against IND‐induced small intestinal injury, at least in part by up‐regulating nrf2‐dependent antioxidant enzymes.
Application of two‐dimensional electrophoresis for plasma of normal and diabetic rats
Authors: Braga Camila Pereira , Pozzi Carla Mariane Costa , Vieira José Cavalcante Souza , do Carmo Federici Padilha Cilene , Okoshi Marina Politi , Fernandes Ana Angélica Henrique , de Magalhães Padilha Pedro 
Published: June 2021

The aim of this study was to compare plasma gels of normal and diabetic rats by two‐dimensional electrophoresis. Experimental animals were randomly divided into two groups (n = 8): G1 = control and G2 = diabetic rats (induced by intraperitoneal administration of streptozotocin in a single dose concentration of 60 mg/kg body weight). A pool of plasma samples were diluted in a specific buffer and applied to IEF (isoelectric focusing) strips with pH in the range of 4–7. Once hydrated for 12h, the strips were brought to the IEF system for running the first dimension. After this step, the strips were equilibrated in a specific buffer for 15 minutes and applied onto polyacrylamide gels at 10% w/v for running the second dimension. At the end of the separation steps (performed in duplicate), the protein spots were fixed in the gel and then stained with Coomassie Blue. The gels were scanned and analyzed using an image processor. For the image analysis, it was found that the protein spots for both experimental groups were more concentrated in the range of 24–76 kDa; 416 spots were found in G1 and 513 in G2, with a percentual matching of 53 and 43% for G1 and G2 respectively. These matching values show that there was some difference between the treatments. There is great interest in the plasma proteome as a discovery source of new biomarkers in diabetes as it is thought to contain subsets of other tissue proteomes.Financial Support: FAPESP 2011/21672–1
Method for Improved Thermal and Chemical Stability of Carotenoids in MonaVie Juice Products
Authors: Quan Danyi , Xiong Maxwell , Pugh Mike , Talbott Shawn 
Published: June 2021

BACKGROUNDCarotenoids, fat‐soluble potent antioxidants, are found in yellow, orange and red fruits and vegetables, and provide protection from free radical damage. However, formulating with carotenoids is difficult because they are susceptible to oxidation and degradation if exposed to oxygen and heat. Ensuring the stability of carotenoids in juices, is a big challenge. To combat this, an effective delivery system is required to ensure the integrity and potency.OBJECTIVEWe used a proprietary microencapsulated carotenoid blend (natural beta‐carotene, lycopene, and lutein). The advantages include the elimination of ingredient cross‐interaction, increased heat stability, and improved shelf‐life and potency.METHODSThe juices were placed on accelerated and long term stability studies. At each time point, the juice samples were extracted and assayed by validated extraction and HPLC methods.RESULTSThe MonaVie Juices with the carotenoid microencapsulated powder blend has an excellent stability profile, suggesting that the carotenoid potency is maintained at least 85% at one year shelf life; compared to only 30% potency of juices containing a commercial granulated beta‐carotene over the same time period.CONCLUSIONThe results show that a microencapsulated powder blend significantly increases the thermal and chemical stabilities of carotenoids in juices, combats the oxidation of carotenoids, and help the carotenoids maintain the potency during the shelf life.