bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of acute exercise on endothelial function in patients with abdominal aortic aneurysm
Authors: Bailey Tom G. , Perissiou Maria , Windsor Mark T. , Schulze Karl , Nam Michael , Magee Rebecca , Leicht Anthony S. , Green Daniel J. , Greaves Kim , Golledge Jonathan , Askew Christopher D. 
Published: September 2017

Endothelial dysfunction is observed in patients with abdominal aortic aneurysm (AAA), who have increased risk of cardiovascular events and mortality. This study aimed to assess the acute effects of moderate- and higher-intensity exercise on endothelial function, as assessed by flow-mediated dilation (FMD), in AAA patients (74 ± 6 yr old, n = 22) and healthy adults (72 ± 5 yr old, n = 22). Participants undertook three randomized visits, including moderate-intensity continuous exercise [40% peak power output (PPO)], higher-intensity interval exercise (70% PPO), and a no-exercise control. Brachial artery FMD was assessed at baseline and at 10 and 60 min after each condition. Baseline FMD was lower [by 1.10% (95% confidence interval: 0.72−.81), P = 0.044] in AAA patients than in healthy adults. There were no group differences in FMD responses after each condition ( P = 0.397). FMD did not change after no-exercise control but increased by 1.21% (95% confidence interval: 0.69−1.73, P < 0.001) 10 min after moderate-intensity continuous exercise in both groups and returned to baseline after 60 min. Conversely, FMD decreased by 0.93% (95% confidence interval: 0.41−1.44, P < 0.001) 10 min after higher-intensity interval exercise in both groups and remained decreased after 60 min. We found that the acute response of endothelial function to exercise is intensity-dependent and similar between AAA patients and healthy adults. Our findings provide evidence that regular exercise may improve vascular function in AAA patients, as it does in healthy adults. Improved FMD after moderate-intensity exercise may provide short-term benefit. Whether the decrease in FMD after higher-intensity exercise represents an additional risk and/or a greater stimulus for vascular adaptation remains to be elucidated. NEW & NOTEWORTHY Abdominal aortic aneurysm patients have vascular dysfunction. We observed a short-term increase in vascular function after moderate-intensity exercise. Conversely, higher-intensity exercise induced a prolonged reduction in vascular function, which may be associated with both short-term increases in cardiovascular risk and signaling for longer-term vascular adaptation in abdominal aortic aneurysm patients.
Muscle metaboreflex-induced vasoconstriction in the ischemic active muscle is exaggerated in heart failure
Authors: Kaur Jasdeep , Senador Danielle , Krishnan Abhinav C. , Hanna Hanna W. , Alvarez Alberto , Machado Tiago M. , O’Leary Donal S. 
Published: September 2017

When oxygen delivery to active muscle is insufficient to meet the metabolic demand during exercise, metabolites accumulate and stimulate skeletal muscle afferents, inducing a reflex increase in blood pressure, termed the muscle metaboreflex. In healthy individuals, muscle metaboreflex activation (MMA) during submaximal exercise increases arterial pressure primarily via an increase in cardiac output (CO), as little peripheral vasoconstriction occurs. This increase in CO partially restores blood flow to ischemic muscle. However, we recently demonstrated that MMA induces sympathetic vasoconstriction in ischemic active muscle, limiting the ability of the metaboreflex to restore blood flow. In heart failure (HF), increases in CO are limited, and metaboreflex-induced pressor responses occur predominantly via peripheral vasoconstriction. In the present study, we tested the hypothesis that vasoconstriction of ischemic active muscle is exaggerated in HF. Changes in hindlimb vascular resistance [femoral arterial pressure ÷ hindlimb blood flow (HLBF)] were observed during MMA (via graded reductions in HLBF) during mild exercise with and without α1-adrenergic blockade (prazosin, 50 µg/kg) before and after induction of HF. In normal animals, initial HLBF reductions caused metabolic vasodilation, while reductions below the metaboreflex threshold elicited reflex vasoconstriction, in ischemic active skeletal muscle, which was abolished after α1-adrenergic blockade. Metaboreflex-induced vasoconstriction of ischemic active muscle was exaggerated after induction of HF. This heightened vasoconstriction impairs the ability of the metaboreflex to restore blood flow to ischemic muscle in HF and may contribute to the exercise intolerance observed in these patients. We conclude that sympathetically mediated vasoconstriction of ischemic active muscle during MMA is exaggerated in HF. NEW & NOTEWORTHY We found that muscle metaboreflex-induced vasoconstriction of the ischemic active skeletal muscle from which the reflex originates is exaggerated in heart failure. This results in heightened metaboreflex activation, which further amplifies the reflex-induced vasoconstriction of the ischemic active skeletal muscle and contributes to exercise intolerance in patients.
Immediate effect of laryngeal surface electrical stimulation on swallowing performance
Authors: Takahashi Keizo , Hori Kazuhiro , Hayashi Hirokazu , Fujiu-Kurachi Masako , Ono Takahiro , Tsujimura Takanori , Magara Jin , Inoue Makoto 
Published: September 2017

Surface electrical stimulation of the laryngeal region is used to improve swallowing in dysphagic patients. However, little is known about how electrical stimulation affects tongue movements and related functions. We investigated the effect of electrical stimulation on tongue pressure and hyoid movement, as well as suprahyoid and infrahyoid muscle activity, in 18 healthy young participants. Electrical stimulation (0.2-ms duration, 80 Hz, 80% of each participant’s maximal tolerance) of the laryngeal region was applied. Each subject swallowed 5 ml of barium sulfate liquid 36 times at 10-s intervals. During the middle 2 min, electrical stimulation was delivered. Tongue pressure, electromyographic activity of the suprahyoid and infrahyoid muscles, and videofluorographic images were simultaneously recorded. Tongue pressure during stimulation was significantly lower than before or after stimulation and was significantly greater after stimulation than at baseline. Suprahyoid activity after stimulation was larger than at baseline, while infrahyoid muscle activity did not change. During stimulation, the position of the hyoid at rest was descended, the highest hyoid position was significantly inferior, and the vertical movement was greater than before or after stimulation. After stimulation, the positions of the hyoid at rest and at the maximum elevation were more superior than before stimulation. The deviation of the highest positions of the hyoid before and after stimulation corresponded to the differences in tongue pressures at those times. These results suggest that surface electrical stimulation applied to the laryngeal region during swallowing may facilitate subsequent hyoid movement and tongue pressure generation after stimulation. NEW & NOTEWORTHY Surface electrical stimulation applied to the laryngeal region during swallowing may facilitate subsequent hyoid movement and tongue pressure generation after stimulation. Tongue muscles may contribute to overshot recovery more than hyoid muscles.
Short-term dietary curcumin supplementation reduces gastrointestinal barrier damage and physiological strain responses during exertional heat stress
Authors: Szymanski Mandy C. , Gillum Trevor L. , Gould Lacey M. , Morin David S. , Kuennen Matthew R. 
Published: September 2017

This work investigated the effect of 3 days of 500 mg/day dietary curcumin supplementation on gastrointestinal barrier damage and systems-physiology responses to exertional heat stress in non-heat-acclimated humans. Eight participants ran (65% V̇o2max) for 60 min in a Darwin chamber (37°C/25% relative humidity) two times (Curcumin/Placebo). Intestinal fatty acid-binding protein (I-FABP) and associated proinflammatory [monocyte chemoattractant protein-1, tumor necrosis factor-α (TNF-α), interleukin-6] and anti-inflammatory [interleukin-1 receptor antagonist (IL-1RA), interleukin-10 (IL-10)] cytokines were assayed from plasma collected before (Pre), after (Post) and 1 (1-Post) and 4 (4-Post) h after exercise. Core temperature and HR were measured throughout exercise; the physiological strain index (PSI) was calculated from these variables. Condition differences were determined with 2-way (condition × time) repeated-measures ANOVAs. The interaction of condition × time was significant ( P = 0.05) for I-FABP and IL-1RA. Post hoc analysis indicated I-FABP increased more from Pre to Post (87%) and 1-Post (33%) in Placebo than in Curcumin (58 and 18%, respectively). IL-1RA increased more from Pre to 1-Post in Placebo (153%) than in Curcumin (77%). TNF-α increased ( P = 0.01) from Pre to Post (19%) and 1-Post (24%) in Placebo but not in Curcumin ( P > 0.05). IL-10 increased ( P < 0.01) from Pre to Post (61%) and 1-Post (42%) in Placebo not in Curcumin ( P > 0.05). The PSI, which indicates exertional heatstroke risk, was also lower ( P < 0.01) in Curcumin than Placebo from 40 to 60 min of exercise. These data suggest 3 days curcumin supplementation may improve gastrointestinal function, associated cytokines, and systems-level physiology responses during exertional heat stress. This could help reduce exertional heatstroke risk in non-heat-acclimated individuals.NEW & NOTEWORTHY Exercise-heat stress increases gastrointestinal barrier damage and risk of exertional heatstroke. Over the past decade at least eight different dietary supplements have been tested for potential improvements in gastrointestinal barrier function and systems-level physiology responses during exercise-heat stress. None have been shown to protect against both insults simultaneously. In this report 3 days of 500 mg/day dietary curcumin supplementation are shown to improve gastrointestinal barrier function, associated cytokine responses, and systems-level physiology parameters. Further research is warranted.
Contribution of structural brain phenotypes to the variance in resting energy expenditure in healthy Caucasian subjects
Authors: Geisler Corinna , Hübers Mark , Granert Oliver , Müller Manfred J. 
Published: September 2017

Brain gray (GM) and white matter (WM) volumes are related to weight changes. The impact of structural variations in GM and WM on the variance in resting energy expenditure (REE) and the REE-on-fat-free mass (FFM) association is unknown. The aim of this study was to address this in healthy Caucasian subjects. Cross-sectional data analysis of 493 healthy Caucasian subjects (age range 6–80 years; 3 age groups) was conducted with comprehensive information on FFM, organ and tissue masses, and detailed brain composition as assessed by whole body magnetic resonance imaging and REE (assessed by indirect calorimetry). REE was calculated (REEc) using organ and tissue masses times their specific metabolic rates. FFM was the major determinant of REE (70.6%); individual masses of liver, total brain, and heart explained a further 2.1% of the variance in REE. Replacing total brain with GM and WM did not change the total R2. Nevertheless, GM added more to the variance in REE (5.6%) and corresponding residuals (12.5%) than did total brain. Additionally, up to 12% was explained by age and sex (<2%). There was a systematic bias between REE and REEc with positive values in younger subjects but negative values in older ones. This bias remained after substituting the specific metabolic rate of brain with the specific metabolic rates of GM and WM. In healthy Caucasian subjects, GM and WM contributed to the variance in REE. Detailed brain structures do not explain the bias between REE and REEc.NEW & NOTEWORTHY Detailed brain composition (gray and white matter) contributed to the variances of resting energy expenditure (REE) and REE-on-fat-free mass residuals. Gray matter explained most of the variances, and for future studies on energy expenditure, brain compartments should be analyzed separately with regard to their different energy needs.
Diabetes Treatments and Risks of Adverse Breast Cancer Outcomes among Early-Stage Breast Cancer Patients: A SEER-Medicare Analysis
Authors: Chen Lu , Chubak Jessica , Boudreau Denise M. , Barlow William E. , Weiss Noel S. , Li Christopher I. 
Published: September 2017

Abstract
The widely prescribed diabetes medicine metformin has been reported to lower the risk of incident breast cancer, but it is unclear whether it affects malignant progression after diagnosis. In this study, we conducted a retrospective cohort study using the linked Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. Women were included in the study if they were aged 66 to 80 years, newly diagnosed with stage I or II breast cancer, and enrolled in Medicare Parts A, B, and D during 2007 to 2011. Information on dispensed diabetes-related medications was obtained from Medicare Part D claims data. Our primary outcomes were second breast cancer events (SBCE), breast cancer recurrence, and breast cancer death. Time-varying Cox proportional hazard models were used to estimate HRs and their 95% confidence intervals (CI). Among 14,766 women included in the study, 791 experienced SBCE, 627 had a recurrence, and 237 died from breast cancer. Use of metformin (n = 2,558) was associated with 28% (95% CI, 0.57–0.92), 31% (95% CI, 0.53–0.90), and 49% (95% CI, 0.33–0.78) lower risks of an SBCE, breast cancer recurrence, and breast cancer death. Use of sulfonylureas or insulin was associated with 1.49- (95% CI, 1.00–2.23) and 2.58-fold (95% CI, 1.72–3.90) higher risks of breast cancer death. Further research may be warranted to determine whether metformin is a preferred treatment for diabetes among breast cancer survivors and whether it benefits breast cancer patients without diabetes. Cancer Res; 77(21); 6033–41. ©2017 AACR.
Melanoma Sequentially Suppresses Different DC Subsets in the Sentinel Lymph Node, Affecting Disease Spread and Recurrence
Authors: van den Hout Mari F.C.M. , Koster Bas D. , Sluijter Berbel J.R. , Molenkamp Barbara G. , van de Ven Rieneke , van den Eertwegh Alfons J.M. , Scheper Rik J. , van Leeuwen Paul A.M. , van den Tol M. Petrousjka , de Gruijl Tanja D. 
Published: September 2017

Abstract
Melanoma exerts immune-suppressive effects to facilitate tumor progression and metastatic spread. We studied these effects on dendritic cell (DC) and T-cell subsets in 36 melanoma sentinel lymph node (SLN) from 28 stage I–III melanoma patients and determined their clinical significance. Four conventional DC subsets, plasmacytoid DCs, and CD4+, CD8+, and regulatory T cells (Tregs), were analyzed by flow cytometry. We correlated these data to clinical parameters and determined their effect on local and distant melanoma recurrence, with a median follow-up of 75 months. In stage I and II melanoma, increased Breslow thickness (i.e., invasion depth of the primary melanoma) was associated with progressive suppression of skin-derived migratory CD1a+ DC subsets. In contrast, LN-resident DC subsets and T cells were only affected once metastasis to the SLN had occurred. In stage III patients, increased CD4:CD8 ratios in concert with the accumulation of Tregs resulted in decreased CD8:Treg ratios. On follow-up, lower frequencies of migratory DC subsets proved related to local melanoma recurrence, whereas reduced maturation of LN-resident DC subsets was associated with distant recurrence and melanoma-specific survival. In conclusion, melanoma-mediated suppression of migratory DC subsets in the SLN precedes local spread, whereas suppression of LN-resident DC subsets follows regional spread and precedes further melanoma dissemination to distant sites. This study offers a rationale to target migratory as well as LN-resident DC subsets for early immunotherapeutic interventions to prevent melanoma recurrence and spread. Cancer Immunol Res; 5(11); 969–77. ©2017 AACR.
Lymphangiogenesis Facilitates Initial Lymph Formation and Enhances the Dendritic Cell Mobilizing Chemokine CCL21 Without Affecting Migration
Authors: Karlsen Tine V. , Reikvam Tore , Tofteberg Anne , Nikpey Elham , Skogstrand Trude , Wagner Marek , Tenstad Olav , Wiig Helge 
Published: September 2017

Objective—
Lymphatic vessels play an important role in body fluid, as well as immune system homeostasis. Although the role of malfunctioning or missing lymphatics has been studied extensively, less is known on the functional consequences of a chronically expanded lymphatic network or lymphangiogenesis.

Approach and Results—
To this end, we used K14-VEGF-C (keratin-14 vascular endothelial growth factor-C) transgenic mice overexpressing the vascular endothelial growth factor C in skin and investigated the responses to inflammatory and fluid volume challenges. We also recorded interstitial fluid pressure, a major determinant of lymph flow. Transgenic mice had a strongly enhanced lymph vessel area in skin. Acute inflammation induced by lipopolysaccharide and chronic inflammation by delayed-type hypersensitivity both resulted in increased interstitial fluid pressure and reduced lymph flow, both to the same extent in wild-type and transgenic mice. Hyperplastic lymphatic vessels, however, demonstrated enhanced transport capacity after local fluid overload not induced by inflammation. In this situation, interstitial fluid pressure was increased to a similar extent in the 2 strains, thus, suggesting that the enhanced lymph vessel area facilitated initial lymph formation. The increased lymph vessel area resulted in an enhanced production of the chemoattractant CCL21 that, however, did not result in augmented dendritic cell migration after induction of local skin inflammation by fluorescein isothiocyanate.

Conclusions—
An expanded lymphatic network is capable of enhanced chemoattractant production, and lymphangiogenesis will facilitate initial lymph formation favoring increased clearance of fluid in situations of augmented fluid filtration.
Perinatal Hypercholesterolemia Exacerbates Atherosclerosis Lesions in Offspring by Altering Metabolism of Trimethylamine-N-Oxide and Bile Acids
Authors: Trenteseaux Charlotte , Gaston Anh-thu , Aguesse Audrey , Poupeau Guillaume , de Coppet Pierre , Andriantsitohaina Ramaroson , Laschet Jamila , Amarger Valérie , Krempf Michel , Nobecourt-Dupuy Estelle , Ouguerram Khadija 
Published: September 2017

Objective—
Experimental studies suggest that maternal hypercholesterolemia may be relevant for the early onset of cardiovascular disease in offspring. We investigated the effect of perinatal hypercholesterolemia on the atherosclerosis development in the offspring of apolipoprotein E–deficient mice and the underlying mechanism.

Approach and Results—

Atherosclerosis and related parameters were studied in adult male or female apolipoprotein E–deficient mice offspring from either normocholesterolemic or hypercholesterolemic mothers and normocholesterolemic fathers. Female born to hypercholesterolemic mothers had more aortic root lesions than female born to normocholesterolemic mothers. Lesions in whole aorta did not differ between groups. Higher trimethylamine-N-oxide levels and
Fmo3
hepatic gene expression were higher in female born to hypercholesterolemic mothers offspring compared with female born to normocholesterolemic mothers and male. Trimethylamine-N-oxide levels were correlated with the size of atherosclerotic root lesions. Levels of hepatic cholesterol and gallbladder bile acid were greater in male born to hypercholesterolemic mothers compared with male born to normocholesterolemic mothers. At 18 weeks of age, female born to hypercholesterolemic mothers showed lower hepatic
Scarb1
and
Cyp7a1
but higher
Nr1h4
gene expression compared with female born to normocholesterolemic mothers. Male born to hypercholesterolemic mothers showed an increase in
Scarb1
and
Ldlr
gene expression compared with male born to normocholesterolemic mothers. At 25 weeks of age, female born to hypercholesterolemic mothers had lower
Cyp7a1
gene expression compared with female born to normocholesterolemic mothers. DNA methylation of
Fmo3, Scarb1
, and
Ldlr
promoter regions was slightly modified and may explain the mRNA expression modulation.

Conclusions—
Our findings suggest that maternal hypercholesterolemia may exacerbate the development of atherosclerosis in female offspring by affecting metabolism of trimethylamine-N-oxide and bile acids. These data could be explained by epigenetic alterations.
Resveratrol Inhibits Growth of Experimental Abdominal Aortic Aneurysm Associated With Upregulation of Angiotensin-Converting Enzyme 2
Authors: Moran Corey S. , Biros Erik , Krishna Smriti M. , Wang Yutang , Tikellis Chris , Morton Susan K. , Moxon Joseph V. , Cooper Mark E. , Norman Paul E. , Burrell Louise M. , Thomas Merlin C. , Golledge Jonathan 
Published: September 2017

Objective—
Recent evidence suggests an important role for angiotensin-converting enzyme 2 (ACE2) in limiting abdominal aortic aneurysm (AAA). This study examined the effect of ACE2 deficiency on AAA development and the efficacy of resveratrol to upregulate ACE2 in experimental AAA.

Approach and Results—

Ace2
deletion in apolipoprotein-deficient mice (
ApoE
−/−
Ace2

−/y

) resulted in increased aortic diameter and spontaneous aneurysm of the suprarenal aorta associated with increased expression of inflammation and proteolytic enzyme markers. In humans, serum ACE2 activity was negatively associated with AAA diagnosis.
ACE2
expression was lower in infrarenal biopsies of patients with AAA than organ donors. AAA was more severe in
ApoE
−/−
Ace2

−/y

mice compared with controls in 2 experimental models. Resveratrol (0.05/100-g chow) inhibited growth of pre-established AAAs in
ApoE
−/−
mice fed high-fat chow and infused with angiotensin II continuously for 56 days. Reduced suprarenal aorta dilatation in mice receiving resveratrol was associated with elevated serum ACE2 and increased suprarenal aorta tissue levels of ACE2 and sirtuin 1 activity. In addition, the relative phosphorylation of Akt and ERK (extracellular signal-regulated kinase) 1/2 within suprarenal aorta tissue and gene expression for nuclear factor of kappa light polypeptide gene enhancer in B cells 1, angiotensin type-1 receptor, and metallopeptidase 2 and 9 were significantly reduced. Upregulation of ACE2 in human aortic smooth muscle cells by resveratrol in vitro was sirtuin 1-dependent.

Conclusions—
This study provides experimental evidence of an important role for ACE2 in limiting AAA development and growth. Resveratrol upregulated ACE2 and inhibited AAA growth in a mouse model.
The European Union’s Reform of Deep-Sea Fisheries in the North-East Atlantic
Authors: Oanta Gabriela A. 
Published: September 2017

Abstract
This article addresses the first reform of the European Union’s legal regime for fishing of deep-sea stocks in the north-east Atlantic and provisions for fishing in international waters of the north-east Atlantic, as adopted through Regulation (eu) 2016/2336. The concept of deep-sea fisheries, a brief description of the work done by the Union so far in relation to the conservation and management of these fish stocks, as well as the specific provisions of this reform are presented.