bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regular walking breaks prevent the decline in cerebral blood flow associated with prolonged sitting
Authors: Carter Sophie E. , Draijer Richard , Holder Sophie M. , Brown Louise , Thijssen Dick H. J. , Hopkins Nicola D. 
Published: June 2018

Decreased cerebrovascular blood flow and function are associated with lower cognitive functioning and increased risk of neurodegenerative diseases. Prolonged sitting impairs peripheral blood flow and function, but its effects on the cerebrovasculature are unknown. This study explored the effect of uninterrupted sitting and breaking up sitting time on cerebrovascular blood flow and function of healthy desk workers. Fifteen participants (10 male, 35.8 ± 10.2 yr, body mass index: 25.5 ± 3.2 kg/m2) completed, on separate days, three 4-h conditions in a randomized order: 1) uninterrupted sitting (SIT), 2) sitting with 2-min light-intensity walking breaks every 30 min (2WALK), or 3) sitting with 8-min light-intensity walking breaks every 2 h (8WALK). At baseline and 4 h, middle cerebral artery blood flow velocity (MCAv) and CO2 reactivity (CVR) of the MCA and carotid artery were measured using transcranial Doppler (TCD) and duplex ultrasound, respectively. Cerebral autoregulation (CA) was assessed with TCD using a squat-stand protocol and analyzed to generate values of gain and phase in the very low, low, and high frequencies. There was a significant decline in SIT MCAv (−3.2 ± 1.2 cm/s) compared with 2WALK (0.6 ± 1.5 cm/s, P = 0.02) but not between SIT and 8WALK (−1.2 ± 1.0 cm/s, P = 0.14). For CA, the change in 2WALK very low frequency phase (4.47 ± 4.07 degrees) was significantly greater than SIT (−3.38 ± 2.82 degrees, P = 0.02). There was no significant change in MCA or carotid artery CVR ( P > 0.05). Results indicate that prolonged uninterrupted sitting in healthy desk workers reduces cerebral blood flow; however, this is offset when frequent short-duration walking breaks are incorporated. NEW & NOTEWORTHY Prolonged uninterrupted sitting in healthy desk workers reduces cerebral blood flow. However, this reduction in cerebral blood flow is offset when frequent short-duration walking breaks are incorporated into this sitting period. For those who engage in long periods of sedentary behavior, chronically breaking up these sitting periods with frequent active break strategies may have important implications for cerebrovascular health; however, further research should explore this hypothesis.
Reciprocal Regulation of DUSP9 and DUSP16 Expression by HIF1 Controls ERK and p38 MAP Kinase Activity and Mediates Chemotherapy-Induced Breast Cancer Stem Cell Enrichment
Authors: Lu Haiquan , Tran Linh , Park Youngrok , Chen Ivan , Lan Jie , Xie Yangyiran , Semenza Gregg L. 
Published: June 2018

Abstract
Triple-negative breast cancer (TNBC) has a poor prognosis due to its aggressive characteristics and lack of targeted therapies. Cytotoxic chemotherapy may reduce tumor bulk, but leaves residual disease due to the persistence of chemotherapy-resistant breast cancer stem cells (BCSC), which are critical for tumor recurrence and metastasis. Here, we demonstrate that hypoxia-inducible factor (HIF)-1–dependent regulation of mitogen-activated protein kinase (MAPK) signaling pathways contributes to chemotherapy-induced BCSC enrichment. Chemotherapy increased DUSP9 expression and decreased DUSP16 expression in a HIF1–dependent manner, leading to inhibition of ERK and activation of p38 signaling pathways, respectively. Inhibition of ERK caused transcriptional induction of the pluripotency factor Nanog through decreased inactivating phosphorylation of FoxO3, while activation of p38 stabilized Nanog and Klf4 mRNA through increased inactivating phosphorylation of RNA-binding protein ZFP36L1, both of which promoted specification of the BCSC phenotype. Inhibition of HIF1 or p38 signaling blocked chemotherapy-induced pluripotency factor expression and BCSC enrichment. These surprising results delineate a mechanism by which a transcription factor switches cells from ERK to p38 signaling in response to chemotherapy and suggest that therapeutic targeting of HIF1 or the p38 pathway in combination with chemotherapy will block BCSC enrichment and improve outcome in TNBC.
Significance: These findings provide a molecular mechanism that may account for the increased relapse rate of women with TNBC who are treated with cytotoxic chemotherapy and suggest that combining chemotherapy with an inhibitor of HIF1 or p38 activity may increase patient survival. Cancer Res; 78(15); 4191–202. ©2018 AACR.
The AAA Risk Factors Scale: A New Model to Screen for the Risk of Asthma, Allergic Rhinitis and Atopic Dermatitis in Children
Authors: Hallit Souheil , Raherison Chantal , Malaeb Diana , Hallit Rabih , Kheir Nelly , Salameh Pascale 
Published: June 2018

<b><i>Objective:</i></b> To create an allergic disease risk factors scale score that would screen for the risk assessment of asthma, allergic rhinitis and atopic dermatitis (AD) in children from 3 to 17 years. <b><i>Methods:</i></b> This case-control study, conducted between December 2015 and April 2016, enrolled 1,274 children. The allergic disease risk factors scale was created by combining environmental, exposure to toxics during pregnancy and breastfeeding and parental history of allergic diseases. <b><i>Results:</i></b> Playing on carpets, male gender, child’s respiratory problems or history of eczema before the age of 2 years, and humidity significantly increased the odds of allergies in the child. Maternal waterpipe smoking, maternal history of rhinitis, history of asthma in the mother or the father, along with the maternal drug intake or alcohol consumption during pregnancy significantly increased the odds of allergies in the child. There was a significant increase in allergy diseases per category of the allergic disease risk factors scale (<i>p</i> &#x3c; 0.001 for trend). Scores ≤2.60 best represented control individuals, while scores &#x3e; 5.31 best represented children with allergic diseases. <b><i>Conclusion:</i></b> Allergic diseases seem to be linked to several risk factors in our population of school children. Many environmental factors might be incriminated in these allergic diseases.
ПРОГНОЗУВАННЯ ВІДДАЛЕНИХ НАСЛІДКІВ ЕНТЕЗИТ-АСОЦІЙОВАНОГО ВАРІАНТУ ЮВЕНІЛЬНОГО ІДІОПАТИЧНОГО АРТРИТУ
Authors: Dzhus M. B. , Marushko T. V. , Nosovets O. K. 
Published: June 2018

Відомо, що ентезит-асоційований варіант ЮІА, в ряді випадків, може призводити до розвитку значних як позасуглобових, так і суглобових пошкоджень. Переважно уражаються кульшові та колінні суглоби з обмеженням їх функції та розвитком анкілозів, що потребує проведення оперативного втручання у цих пацієнтів, а також часто розвивається катаракта та сліпота через ураження очей в дитячому віці. Нашою метою було оцінити фактори ризику розвитку в дорослому віці суглобових та позасуглобових пошкоджень при о ентезит-асоційованому варіанті ЮІА та розробити прогностичну модель їх розвитку. Матеріали та методи дослідження. В дослідження включено 21 дорослих пацієнтів з ентезит-асоційованим варіантом ЮІА. Ретроспективно проаналізовано медичну документацію пацієнтів з ентезит-асоційованим варіантом ЮІА, з врахуванням клінічних проявів в дебюті захворювання, лабораторних показників та відповідь на проведену терапію. В дорослому віці для оцінки віддалених наслідків ЮІА використовували інтегральний індекс пошкодження суглобових (JADI-A) та позасуглобових (JADI-E) уражень.Результати досліджень. Методом бінарної логістичної регресії виявлено фактори несприятливого прогнозу та розроблено математичну модель прогнозування ймовірності виникнення віддалених негативних наслідків ентезит-асоційованого ЮІА у вигляді суглобових та позасуглобових уражень. Висновки. 1. Факторами ризику розвитку суглобових та позасуглобових пошкоджень в дорослому віці у пацієнтів з ентезит-асоційованим варіантом ЮІА є вік пацієнта на початку захворювання, час відтермінування встановлення діагнозу, наявність в дитинстві дактилітів, симетричного артриту, болю в хребті, активність за JADAS в дитинстві, прийом глюкокортикоїдів, потреба в інтенсифікації терапії. 2. Розроблено прогностичну модель розвитку суглобових та позасуглобових пошкоджень в дорослому віці у пацієнтів з ентезит-асоційованим варіантом ЮІА. Заявлений спосіб прогнозування віддалених наслідків ентезит-асоційованого варіанту ЮІА у дорослому віці є ефективним, що дозволяє визначити несприятливий перебіг захворювання та може стати основою до персоніфікованого лікування для запобігання розвитку значних суглобових та позасуглобових пошкоджень в наслідок ЮІА у дорослому віці.
ЕРАДИКАЦІЯ HELICOBACTER PYLORI У ХВОРИХ З ХРОНІЧНИМ ГАСТРИТОМ ТА ЦУКРОВИМ ДІАБЕТОМ ІІ ТИПУ
Authors: Sirchak E. S. , Patskun S. V. 
Published: June 2018

Вступ. Helicobacter pylori (НР) є основним бактеріальним патогеном людини, що призводить до розвитку хронічної інфекції та може викликати ряд захворювань верхніх відділів шлунково-кишкового тракту. Поширеність HР є значно вищою у хворих з цукровим діабетом (ЦД) ІІ типу в порівнянні з пацієнтами без ЦД ІІ типу.Мета. Оцінити ефективність використання SВ в комплексній антигелікобактерній терапії (АГТ) у хворих з хронічним гастритом (ХГ) в поєднанні з ЦД II типу.Матеріали і методи. Обстежено 42 НP позитивних хворих з поєднанням ХГ та ЦД ІІ типу. Середній вік пацієнтів склав 53,6±1,4 років. Серед хворих 13 (30,9%) жінок та 29 (69,1 %) чоловіків. Хворих розділили на 2 групи: I група (n=21) отримувала тільки стандартну АГТ, II група (n=21) додатково до АГТ отримувала препарат SВ (Нормагут, фірми Mega) по 2 капсули 2 рази на день - 14 днів.Результати дослідження. Отримано наступні результати, а саме виявлено, що інсулінорезистентність залежить від наявності в організмі НР і її ерадикація в подальшому призводить до покращення чутливості до інсуліну. При аналізі скарг обстежених пацієнтів до проведення та наприкінці 2 тижня АГТ виявлено покращення стану хворих з ІІ групи, що приймали додатково до стандартної терапії SB. Проведені нами дослідження дають змогу також стверджувати, що ефективна ерадикація НР сприяє покращенню контролю рівня глюкози у хворих на ЦД ІІ типу та ХГ.Висновки. Ерадикаця НР є важливою у пацієнтів з ЦД ІІ типу та ХГ, оскільки проведення АГТ сприяє покращенню чутливості до інсуліну.
ПІДХОДИ ЩОДО РОЗВИТКУ ПАЛІАТВИНОЇ ТА ХОСПІСНОЇ ДОПОМОГИ
Authors: Kurnytska H. M. 
Published: June 2018

У статті розглянуто та висвітлено питання, повязані з розвитком паліативної та хоспісної допомоги в Україні, а саме, відділення паліативного та хоспісних лікувально-профілактичних закладів є вкрай обмежені ресурси та не мають можливості забезпечити хворих навіть найнеобхіднішим. Важливою проблемою є створення в Україні системи підготовки кадрів, які беруть участь у наданні послуг паліативної та хоспісної допомоги. Обов’язок держави забезпечити доступ до паліативної допомоги всім пацієнтам, незалежно від віку, нозологічної категорії захворювання, соціального статусу, національності, релігійних та політичних переконань, місця перебування тощо. Якщо суспільство вважає себе цивілізованим, то неодмінно зобов’язане подбати про те, щоб невиліковно хворі отримали якісний і належний догляд. Байдуже суспільство немає майбутнього!
VEGF (Vascular Endothelial Growth Factor) Induces NRP1 (Neuropilin-1) Cleavage via ADAMs (a Disintegrin and Metalloproteinase) 9 and 10 to Generate Novel Carboxy-Terminal NRP1 Fragments That Regulate Angiogenic Signaling
Authors: Mehta Vedanta , Fields Laura , Evans Ian M. , Yamaji Maiko , Pellet-Many Caroline , Jones Timothy , Mahmoud Marwa , Zachary Ian 
Published: June 2018

Objective—
NRP1(neuropilin-1) acts as a coreceptor for VEGF (vascular endothelial growth factor) with an essential role in angiogenesis. Recent findings suggest that posttranslational proteolytic cleavage of VEGF receptors may be an important mechanism for regulating angiogenesis, but the role of NRP1 proteolysis and the NRP1 species generated by cleavage in endothelial cells is not known. Here, we characterize NRP1 proteolytic cleavage in endothelial cells, determine the mechanism, and investigate the role of NRP1 cleavage in regulation of endothelial cell function.

Approach and Results—

NRP1 species comprising the carboxy (C)-terminal and transmembrane NRP1 domains but lacking the ligand-binding A and B regions are constitutively expressed in endothelial cells. Generation of these C-terminal domain NRP1 proteins is upregulated by phorbol ester and Ca
2+
ionophore, and reduced by pharmacological inhibition of metalloproteinases, by small interfering RNA-mediated knockdown of 2 members of ADAM (a disintegrin and metalloproteinase) family, ADAMs 9 and 10, and by a specific ADAM10 inhibitor. Furthermore, VEGF upregulates expression of these NRP1 species in an ADAM9/10-dependent manner. Transduction of endothelial cells with adenoviral constructs expressing NRP1 C-terminal domain fragments inhibited VEGF-induced phosphorylation of VEGFR2 (VEGF receptor tyrosine kinase)/KDR (kinase domain insert receptor) and decreased VEGF-stimulated endothelial cell motility and angiogenesis in coculture and aortic ring sprouting assays.

Conclusions—
These findings identify novel NRP1 species in endothelial cells and demonstrate that regulation of NRP1 proteolysis via ADAMs 9 and 10 is a new regulatory pathway able to modulate VEGF angiogenic signaling.
Role of 3-Dimensional Architecture of Scar and Surviving Tissue in Ventricular Tachycardia
Authors: Pashakhanloo Farhad , Herzka Daniel A. , Halperin Henry , McVeigh Elliot R. , Trayanova Natalia A. 
Published: June 2018

Background:
An improved knowledge of the spatial organization of infarct structure and its contribution to ventricular tachycardia (VT) is important for designing optimal treatments. This study explores the relationship between the 3-dimensional structure of the healed infarct and the VT reentrant pathways in high-resolution models of infarcted porcine hearts.

Methods:

Structurally detailed models of infarcted ventricles were reconstructed from ex vivo late gadolinium enhancement and diffusion tensor magnetic resonance imaging data of 8 chronically infarcted porcine hearts at submillimeter resolution (0.25×0.25×0.5 mm
3
). To characterize the 3-dimensional structure of surviving tissue in the zone of infarct, a novel scar-mapped thickness metric was introduced. Further, using the ventricular models, electrophysiological simulations were conducted to determine and analyze the 3-dimensional VT pathways that were established in each of the complex infarct morphologies.

Results:
The scar-mapped thickness metric revealed the heterogeneous organization of infarct and enabled us to systematically characterize the distribution of surviving tissue thickness in 8 hearts. Simulation results demonstrated the involvement of a subendocardial tissue layer of varying thickness in the majority of VT pathways. Importantly, they revealed that VT pathways are most frequently established within thin surviving tissue structures of thickness ≤2.2 mm (90th percentile) surrounding the scar.

Conclusions:
The combination of high-resolution imaging data and ventricular simulations revealed the 3-dimensional distribution of surviving tissue surrounding the scar and demonstrated its involvement in VT pathways. The new knowledge obtained in this study contributes toward a better understanding of infarct-related VT.
High Serum Level of Matrix Metalloproteinase-7 Is Associated With Increased Risk of Spontaneous Subarachnoid Hemorrhage
Authors: Söderholm Martin , Nordin Fredrikson Gunilla , Nilsson Jan , Engström Gunnar 
Published: June 2018

Background and Purpose—
Increased degradation of the extracellular matrix in the arterial wall by matrix metalloproteinases (MMPs) may be an important mechanism in the pathogenesis of intracranial aneurysms and subarachnoid hemorrhage (SAH). MMP-2 and MMP-9 have been suggested to be involved in matrix degradation preceding SAH. We studied serum levels of MMP-1, -2, -3, -7, -9, -10, and -12 and the risk of incident SAH.

Methods—
A nested case–control study within the population-based cohort, Malmö Diet and Cancer study, was performed including incident cases of spontaneous SAH (n=79) and controls matched by age, sex, and follow-up time (n=232). MMPs were measured in serum from the baseline examination in 1991 to 1996. MMPs were compared between cases and controls, using conditional logistic regression adjusting for risk factors.

Results—

Baseline levels of MMP-7, MMP-10, and MMP-12 were significantly higher in incident SAH cases compared with controls. Odds ratios (95% confidence interval) for SAH per 1 SD increase of MMP-7, MMP-10, and MMP-12 were 1.78 (1.31–2.41), 1.45 (1.11–1.91), and 1.53 (1.17–2.01), respectively. After adjustment for SAH risk factors, MMP-7 was still significantly associated with SAH (odds ratio: 1.64; 95% confidence interval: 1.19–2.27;
P
=0.0026), whereas associations for MMP-10 and MMP-12 were attenuated and nonsignificant. We did not find any association between high serum levels of MMP-2 or MMP-9 and SAH risk.

Conclusions—
High serum level of MMP-7 was associated with increased risk of incident spontaneous SAH, independently of the main risk factors for SAH. High serum levels of MMP-2 and MMP-9 did not predict SAH risk.
Does the type of cardioplegia used during valve surgery influence operative nadir hematocrit and transfusion requirements?
Authors: Stammers Alfred H. , Tesdahl Eric A. , Mongero Linda B. , Stasko Andrew 
Published: June 2018

Introduction: Myocardial protection is performed using diverse cardioplegic (CP) solutions with various combinations of chemical and blood constituents. Newer CP formulations that extend ischemic intervals may require greater asanguineous volume, contributing to hemodilution. Methods: We evaluated intraoperative hemodilution and red blood cell (RBC) transfusion rates among three common CP solutions during cardiac valve surgery. Data from 5,830 adult cardiac primary valve procedures where either four-to-one blood CP (4:1), del Nido solution (DN) or microplegia (MP) was used at 173 United States surgical centers. The primary outcome was the nadir hematocrit (Hct) during cardiopulmonary bypass (CPB), with a secondary outcome of total units of RBC transfused intraoperatively. Outcomes were assessed using mixed-effects regression, with controls for patient size, age, first Hct in the operating room, ultrafiltration volume, net bypass circuit priming volume, anesthesia and perfusion asanguineous volumes, cross-clamp and total procedure times, procedure type, reoperation, hospital, surgeon and twelve other patient and procedural variables. Results: A total of 2,641 patients received 4:1 (45.3%), 1,864 received DN (32.0%) and 1,325 received MP (22.7%). There were only slight differences in the central tendency (mean (SD)) for crude nadir Hct on CPB: 4:1, 25.5 (4.5), DN, 26.0 (4.6) and MP, 26.5 (4.7). After controlling for numerous operative and patient characteristics, the regression-adjusted estimate of the nadir Hct on CPB for MP was 26.2%, compared to 25.7% for 4:1 and 25.7% for DN; differences between MP and the other methods were statistically significant (p<0.01). Unadjusted mean RBC units transfused per patient was very similar across the groups (4:1, 2.2; MP, 2.3; DN, 2.4). Regression-adjusted estimates for the number of units of RBC transfused intraoperatively showed no statistically significant differences between CP methods. Conclusions: In patients undergoing cardiac valve surgery, the type of CP did not have a strong clinical impact on hemodilution or transfusion. Choice of a myocardial preservation solution can be made independently of its effect on intraoperative Hct.
Traumatic aortic injury presenting to an adult major trauma centre
Authors: Bade-Boon Jordan , Mathew Joseph K , Fitzgerald Mark C , Mitra Biswadev 
Published: June 2018

Introduction Traumatic aortic injury is an uncommon condition. Timely diagnosis may enable early haemostatic resuscitation, essential to prevent worsening of the injury prior to definitive management. The aim of this study was to assess the utility of initial vital signs and presenting clinical characteristics to confirm or rule out aortic injury. Methods A retrospective review of patients from The Alfred Trauma Registry was conducted. Patients presenting between January 2006 and July 2014 and diagnosed with aortic injury were identified. Demographics and presenting clinical characteristics were extracted. Sensitivity of individual clinical variables for the detection of aortic injury was calculated. Results There were 77 patients identified with aortic injury, with an in-hospital mortality rate of 19.5% (95% CI: 10.6–28.3%). Of these, 68 (88.3%) patients presented after high-energy blunt mechanisms. Clinical signs and early chest X-ray findings were poorly sensitive to detect aortic injury. Patients who presented with hypotension had a greater severity of aortic injury, more commonly had associated abnormal investigation findings and were more likely to require blood products and inotropic agents (p < 0.05). However, sensitivity of initial hypotension to rule out aortic injury was 39.0% (95% CI: 28.1–49.9%). Conclusions The diagnosis of aortic injury was uncommon in hospital. Most injuries were secondary to high-velocity road traffic crashes or high falls. Clinical signs were not adequately sensitive to be used for the exclusion of aortic injury. We recommend a high degree of clinical suspicion and liberal imaging among cases where aortic injury is possible.
Influence of Maximal Running Shoes on Biomechanics Before and After a 5K Run
Authors: Pollard Christine D. , Ter Har Justin A. , Hannigan J.J. , Norcross Marc F. 
Published: June 2018

Background: Lower extremity injuries are common among runners. Recent trends in footwear have included minimal and maximal running shoe types. Maximal running shoes are unique because they provide the runner with a highly cushioned midsole in both the rearfoot and forefoot. However, little is known about how maximal shoes influence running biomechanics. Purpose: To examine the influence of maximal running shoes on biomechanics before and after a 5-km (5K) run as compared with neutral running shoes. Study Design: Controlled laboratory study. Methods: Fifteen female runners participated in 2 testing sessions (neutral shoe session and maximal shoe session), with 7 to 10 days between sessions. Three-dimensional kinematic and kinetic data were collected while participants ran along a 10-m runway. After 5 running trials, participants completed a 5K treadmill run, followed by 5 additional running trials. Variables of interest included impact peak of the vertical ground-reaction force, loading rate, and peak eversion. Differences were determined by use of a series of 2-way repeated-measures analysis of variance models (shoe × time). Results: A significant main effect was found for shoe type for impact peak and loading rate. When the maximal shoe was compared with the neutral shoe before and after the 5K run, participants exhibited an increased loading rate (mean ± SE: pre–maximal shoe, 81.15 body weights/second [BW/s] and pre–neutral shoe, 60.83 BW/s [ P < .001]; post–maximal shoe, 79.10 BW/s and post–neutral shoe, 61.22 BW/s [ P = .008]) and increased impact peak (pre–maximal shoe, 1.76 BW and pre–neutral shoe, 1.58 BW [ P = .004]; post–maximal shoe, 1.79 BW and post–neutral shoe, 1.55 BW [ P = .003]). There were no shoe × time interactions and no significant findings for peak eversion. Conclusion: Runners exhibited increased impact forces and loading rate when running in a maximal versus neutral shoe. Because increases in these variables have been associated with an increased risk of running-related injuries, runners who are new to running in a maximal shoe may be at an increased risk of injury. Clinical Relevance: Understanding the influence of running footwear as an intervention that affects running biomechanics is important for clinicians so as to reduce patient injury.