bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Na+/K+‐ATPase and KIR channels abolishes hypoxic hyperaemia in resting but not contracting skeletal muscle of humans
Authors: Racine Matthew L. , Crecelius Anne R. , Luckasen Gary J. , Larson Dennis G. , Dinenno Frank A. 
Published: March 2018

Key points
Increasing blood flow (hyperaemia) to exercising muscle helps match oxygen delivery and metabolic demand. During exercise in hypoxia, there is a compensatory increase in muscle hyperaemia that maintains oxygen delivery and tissue oxygen consumption.
Nitric oxide (NO) and prostaglandins (PGs) contribute to around half of the augmented hyperaemia during hypoxic exercise, although the contributors to the remaining response are unknown.
In the present study, inhibiting NO, PGs, Na+/K+‐ATPase and inwardly rectifying potassium (KIR) channels did not blunt augmented hyperaemia during hypoxic exercise beyond previous observations with NO/PG block alone. Furthermore, although inhibition of only Na+/K+‐ATPase and KIR channels abolished hyperaemia during hypoxia at rest, it had no effect on augmented hyperaemia during hypoxic exercise.
This is the first study in humans to demonstrate that Na+/K+‐ATPase and KIR channel activation is required for augmented muscle hyperaemia during hypoxia at rest but not during hypoxic exercise, thus providing new insight into vascular control.
AbstractExercise hyperaemia in hypoxia is augmented relative to the same exercise intensity in normoxia. During moderate‐intensity handgrip exercise, endothelium‐derived nitric oxide (NO) and vasodilating prostaglandins (PGs) contribute to ∼50% of the augmented forearm blood flow (FBF) response to hypoxic exercise (HypEx), although the mechanism(s) underlying the remaining response are unclear. We hypothesized that combined inhibition of NO, PGs, Na+/K+‐ATPase and inwardly rectifying potassium (KIR) channels would abolish the augmented hyperaemic response in HypEx. In healthy young adults, FBF responses were measured (Doppler ultrasound) and forearm vascular conductance was calculated during 5 min of rhythmic handgrip exercise at 20% maximum voluntary contraction under regional sympathoadrenal inhibition in normoxia and isocapnic HypEx (O2 saturation ∼80%). Compared to control, combined inhibition of NO, PGs, Na+/K+‐ATPase and KIR channels (l‐NMMA + ketorolac + ouabain + BaCl2; Protocol 1; n = 10) blunted the compensatory increase in FBF during HypEx by ∼50% (29 ± 6 mL min−1 vs. 62 ± 8 mL min−1, respectively, P < 0.05). By contrast, ouabain + BaCl2 alone (Protocol 2; n = 10) did not affect this augmented hyperaemic response (50 ± 11 mL min−1 vs. 60 ± 13 mL min−1, respectively, P > 0.05). However, the blocked condition in both protocols abolished the hyperaemic response to hypoxia at rest (P < 0.05). We conclude that activation of Na+/K+‐ATPase and KIR channels is involved in the hyperaemic response to hypoxia at rest, although it does not contribute to the augmented exercise hyperaemia during hypoxia in humans.
Moderate and severe hypoxia elicit divergent effects on cardiovascular function and physiological rhythms
Authors: Allwood Melissa A. , Edgett Brittany A. , Eadie Ashley L. , Huber Jason S. , Romanova Nadya , Millar Philip J. , Brunt Keith R. , Simpson Jeremy A. 
Published: March 2018

Key points
In the present study, we provide evidence for divergent physiological responses to moderate compared to severe hypoxia, addressing an important knowledge gap related to severity, duration and after‐effects of hypoxia encountered in cardiopulmonary situations.
The physiological responses to moderate and severe hypoxia were not proportional, linear or concurrent with the time‐of‐day.
Hypoxia elicited severity‐dependent physiological responses that either persisted or fluctuated throughout normoxic recovery.
The physiological basis for these distinct cardiovascular responses implicates a shift in the sympathovagal set point and probably not molecular changes at the artery resulting from hypoxic stress.
AbstractHypoxia is both a consequence and cause of many acute and chronic diseases. Severe hypoxia causes hypertension with cardiovascular sequelae; however, the rare studies using moderate severities of hypoxia indicate that it can be beneficial, suggesting that hypoxia may not always be detrimental. Comparisons between studies are difficult because of the varied classifications of hypoxic severities, methods of delivery and use of anaesthetics. Thus, to investigate the long‐term effects of moderate hypoxia on cardiovascular health, radiotelemetry was used to obtain in vivo physiological measurements in unanaesthetized mice during 24 h of either moderate or severe hypoxia, followed by 72 h of normoxic recovery. Systolic blood pressure was decreased during recovery following moderate hypoxia but increased following severe hypoxia. Moderate and severe hypoxia increased haeme oxygenase‐1 expression during recovery, suggesting parity in hypoxic stress at the level of the artery. Severe but not moderate hypoxia increased the low/high frequency ratio of heart rate variability 72 h post‐hypoxia, indicating a shift in sympathovagal balance. Moderate hypoxia dampened the amplitude of circadian rhythm, whereas severe disrupted rhythm during the entire insult, with perturbations persisting throughout normoxic recovery. Thus, hypoxic severity differentially regulates circadian blood pressure.
Stable Isotope Probing for Microbial Iron Reduction in Chocolate Pots Hot Spring, Yellowstone National Park
Authors: Fortney Nathaniel W. , He Shaomei , Kulkarni Ajinkya , Friedrich Michael W. , Holz Charlotte , Boyd Eric S. , Roden Eric E. 
Published: March 2018

ABSTRACT

Chocolate Pots hot springs (CP) is a circumneutral-pH Fe-rich geothermal feature located in Yellowstone National Park. Previous Fe(III)-reducing enrichment culture studies with CP sediments identified close relatives of known dissimilatory Fe(III)-reducing bacterial (FeRB) taxa, including
Geobacter
and
Melioribacter
. However, the abundances and activities of such organisms in the native microbial community are unknown. Here, we used stable isotope probing experiments combined with 16S rRNA gene amplicon and shotgun metagenomic sequencing to gain an understanding of the
in situ
Fe(III)-reducing microbial community at CP. Fe-Si oxide precipitates collected near the hot spring vent were incubated with unlabeled and
13
C-labeled acetate to target active FeRB. We searched reconstructed genomes for homologs of genes involved in known extracellular electron transfer (EET) systems to identify the taxa involved in Fe redox transformations. Known FeRB taxa containing putative EET systems (
Geobacter
,
Ignavibacteria
) increased in abundance under acetate-amended conditions, whereas genomes related to
Ignavibacterium
and
Thermodesulfovibrio
that contained putative EET systems were recovered from incubations without electron donor. Our results suggest that FeRB play an active role in Fe redox cycling within Fe-Si oxide-rich deposits located at the hot spring vent.

IMPORTANCE
The identification of past near-surface hydrothermal environments on Mars emphasizes the importance of using modern Earth environments, such as CP, to gain insight into potential Fe-based microbial life on other rocky worlds, as well as ancient Fe-rich Earth ecosystems. By combining stable carbon isotope probing techniques and DNA sequencing technology, we gained insight into the pathways of microbial Fe redox cycling at CP. The results suggest that microbial Fe(III) oxide reduction is prominent
in situ
, with important implications for the generation of geochemical and stable Fe isotopic signatures of microbial Fe redox metabolism within Fe-rich circumneutral-pH thermal spring environments on Earth and Mars.
Comparison of an
In Vitro
Diagnostic Next-Generation Sequencing Assay with Sanger Sequencing for HIV-1 Genotypic Resistance Testing
Authors: Tzou Philip L. , Ariyaratne Pramila , Varghese Vici , Lee Charlie , Rakhmanaliev Elian , Villy Carolin , Yee Meiqi , Tan Kevin , Michel Gerd , Pinsky Benjamin A. , Shafer Robert W. 
Published: March 2018

ABSTRACT

The ability of next-generation sequencing (NGS) technologies to detect low frequency HIV-1 drug resistance mutations (DRMs) not detected by dideoxynucleotide Sanger sequencing has potential advantages for improved patient outcomes. We compared the performance of an
in vitro
diagnostic (IVD) NGS assay, the Sentosa SQ HIV genotyping assay for HIV-1 genotypic resistance testing, with Sanger sequencing on 138 protease/reverse transcriptase (RT) and 39 integrase sequences. The NGS assay used a 5% threshold for reporting low-frequency variants. The level of complete plus partial nucleotide sequence concordance between Sanger sequencing and NGS was 99.9%. Among the 138 protease/RT sequences, a mean of 6.4 DRMs was identified by both Sanger and NGS, a mean of 0.5 DRM was detected by NGS alone, and a mean of 0.1 DRM was detected by Sanger sequencing alone. Among the 39 integrase sequences, a mean of 1.6 DRMs was detected by both Sanger sequencing and NGS and a mean of 0.15 DRM was detected by NGS alone. Compared with Sanger sequencing, NGS estimated higher levels of resistance to one or more antiretroviral drugs for 18.2% of protease/RT sequences and 5.1% of integrase sequences. There was little evidence for technical artifacts in the NGS sequences, but the G-to-A hypermutation was detected in three samples. In conclusion, the IVD NGS assay evaluated in this study was highly concordant with Sanger sequencing. At the 5% threshold for reporting minority variants, NGS appeared to attain a modestly increased sensitivity for detecting low-frequency DRMs without compromising sequence accuracy.
Evaluation of choroidal lesions with swept-source optical coherence tomography
Authors: Ung Cindy , Laíns Inês , Silverman Rebecca F , Woods Russell , Lane Anne Marie , Papakostas Thanos D , Husain Deeba , Miller Joan W , Gragoudas Evangelos S , Kim Ivana K , Miller John B 
Published: March 2018

AimsThe aim of our study was to image choroidal lesions with swept-source optical coherence tomography (SS-OCT) and to identify the morphological characteristics associated with optimal visualisation.MethodsThis was a prospective, cross-sectional study. Patients with choroidal melanocytic lesions <3 mm in thickness on B-scan ultrasonography were recruited. All participants underwent SS-OCT. On SS-OCT we evaluated qualitative (eg, lesion outline, detection of scleral-choroidal interface and quality of the image) and quantitative (measurement of maximum lesion thickness and the largest basal diameter) parameters. Probability of optimal image quality was examined using ordered logistic regression models. The main outcome measure was quality of the choroidal lesion images on SS-OCT, defined as: optimal, suboptimal or poor.ResultsWe included 85 choroidal lesions of 82 patients. There were 24 choroidal lesions (29%) for which image quality was classified as optimal, 31 lesions (37%) as suboptimal and 30 lesions (36%) as poor. The factors associated with optimal image quality were distance closer to the fovea (OR 0.76, p<0.001), posterior pole location (OR 3.87, p=0.05), lower ultrasonography thickness (OR 0.44, p=0.04), lighter lesion pigmentation (OR 0.12, p=0.003) and smaller lesion diameter (OR 0.73, p<0.001). In the multivariable analysis, closer distance to the fovea (OR 0.81, p=0.005), lighter lesion pigmentation (OR 0.11, p=0.01) and smaller lesion diameter (OR 0.76, p=0.006) remained statistically significant.ConclusionSS-OCT is useful in imaging most choroidal melanocytic lesions. Image quality is best when the choroidal lesion is closer to the fovea, has a smaller diameter and a lighter choroidal pigmentation.
Assessing the health effects associated with occupational radiation exposure in Korean radiation workers: protocol for a prospective cohort study
Authors: Seo Songwon , Lim Wan Young , Lee Dal Nim , Kim Jung Un , Cha Eun Shil , Bang Ye Jin , Lee Won Jin , Park Sunhoo , Jin Young Woo 
Published: March 2018

IntroductionThe cancer risk of radiation exposure in the moderate-to-high dose range has been well established. However, the risk remains unclear at low-dose ranges with protracted low-dose rate exposure, which is typical of occupational exposure. Several epidemiological studies of Korean radiation workers have been conducted, but the data were analysed retrospectively in most cases. Moreover, groups with relatively high exposure, such as industrial radiographers, have been neglected. Therefore, we have launched a prospective cohort study of all Korean radiation workers to assess the health effects associated with occupational radiation exposure.Methods and analysisApproximately 42 000 Korean radiation workers registered with the Nuclear Safety and Security Commission from 2016 to 2017 are the initial target population of this study. Cohort participants are to be enrolled through a nationwide self-administered questionnaire survey between 24 May 2016 and 30 June 2017. As of 31 March 2017, 22 982 workers are enrolled in the study corresponding to a response rate of 75%. This enrolment will be continued at 5-year intervals to update information on existing study participants and recruit newly hired workers. Survey data will be linked with the national dose registry, the national cancer registry, the national vital statistics registry and national health insurance data via personal identification numbers. Age-specific and sex-specific standardised incidence and mortality ratios will be calculated for overall comparisons of cancer risk. For dose–response assessment, excess relative risk (per Gy) and excess absolute risk (per Gy) will be estimated with adjustments for birth year and potential confounders, such as lifestyle factors and socioeconomic status.Ethics and disseminationThis study has received ethical approval from the institutional review board of the Korea Institute of Radiological and Medical Sciences (IRB No. K-1603-002-034). All participants provided written informed consent prior to enrolment. The findings of the study will be disseminated through scientific peer-reviewed journals and be provided to the public, including radiation workers, via the study website (http://www.rhs.kr/) and onsite radiation safety education.
Protocol to assess the impact of tobacco-induced volatile organic compounds on cardiovascular risk in a cross- sectional cohort: Cardiovascular Injury due to Tobacco Use study
Authors: Keith Rachel J , Fetterman Jessica L , Riggs Daniel W , O’Toole Timothy , Nystoriak Jessica L , Holbrook Monika , Lorkiewicz Pawel , Bhatnagar Aruni , DeFilippis Andrew P , Hamburg Naomi M 
Published: March 2018

IntroductionTobacco use leads to increased mortality, the majority of which is attributed to cardiovascular disease. Despite this knowledge, the early cardiovascular impact of tobacco product use is not well understood. Tobacco use increases exposure to harmful and potentially harmful constituents including volatile organic compounds (VOCs) such as acrolein and crotonaldehyde, which may contribute to cardiovascular risk. The link between exposure patterns, risk profiles and demographic distribution of tobacco product users, particularly users of new and emerging products, are not well known. Therefore, we designed the Cardiovascular Injury due to Tobacco Use (CITU) study to assess population characteristics, demographic features, exposure patterns and cardiovascular risk in relation to tobacco.Methods and analysisWe present the design and methodology of the CITU study, a cross-sectional observational tobacco study conducted in Boston, Massachusetts and Louisville, Kentucky starting in 2014. Healthy participants 21–45 years of age who use tobacco products, including electronic nicotine devices, or who never used tobacco are being recruited. The study aims to recruit an evenly split cohort of African-Americans and Caucasians, that is, sex balanced for evaluation of self-reported tobacco exposure, VOC exposure and tobacco-induced injury profiling. Detailed information about participant’s demographics, health status and lifestyle is also collected.Ethics and disseminationThe study protocol was approved institutional review boards at both participating universities. All study protocols will protect participant confidentiality. Results from the study will be disseminated via peer-reviewed journals and presented at scientific conferences.
Factors associated with 30-day readmission after hospitalisation for community-acquired pneumonia in older patients: a cross-sectional study in seven Spanish regions
Authors: Toledo Diana , Soldevila Núria , Torner Núria , Pérez-Lozano María José , Espejo Elena , Navarro Gemma , Egurrola Mikel , Domínguez Ángela 
Published: March 2018

ObjectiveHospital readmission in patients admitted for community-acquired pneumonia (CAP) is frequent in the elderly and patients with multiple comorbidities, resulting in a clinical and economic burden. The aim of this study was to determine factors associated with 30-day readmission in patients with CAP.DesignA cross-sectional study.SettingThe study was conducted in patients admitted to 20 hospitals in seven Spanish regions during two influenza seasons (2013–2014 and 2014–2015).ParticipantsWe included patients aged ≥65 years admitted through the emergency department with a diagnosis compatible with CAP. Patients who died during the initial hospitalisation and those hospitalised more than 30 days were excluded. Finally, 1756 CAP cases were included and of these, 200 (11.39%) were readmitted.Main outcome measures30-day readmission.ResultsFactors associated with 30-day readmission were living with a person aged <15 years (adjusted OR (aOR) 2.10, 95% CI 1.01 to 4.41), >3 hospital visits during the 90 previous days (aOR 1.53, 95% CI 1.01 to 2.34), chronic respiratory failure (aOR 1.74, 95% CI 1.24 to 2.45), heart failure (aOR 1.69, 95% CI 1.21 to 2.35), chronic liver disease (aOR 2.27, 95% CI 1.20 to 4.31) and discharge to home with home healthcare (aOR 5.61, 95% CI 1.70 to 18.50). No associations were found with pneumococcal or seasonal influenza vaccination in any of the three previous seasons.ConclusionsThis study shows that 11.39% of patients aged ≥65 years initially hospitalised for CAP were readmitted within 30 days after discharge. Rehospitalisation was associated with preventable and non-preventable factors.
Incidence of adverse events in Sweden during 2013–2016: a cohort study describing the implementation of a national trigger tool
Authors: Nilsson Lena , Borgstedt-Risberg Madeleine , Soop Michael , Nylén Urban , Ålenius Carina , Rutberg Hans 
Published: March 2018

ObjectivesTo describe the implementation of a trigger tool in Sweden and present the national incidence of adverse events (AEs) over a 4-year period during which an ongoing national patient safety initiative was terminated.DesignCohort study using retrospective record review based on a trigger tool methodology.Setting and participantsPatients ≥18 years admitted to all somatic acute care hospitals in Sweden from 2013 to 2016 were randomised into the study.Primary and secondary outcome measuresPrimary outcome measure was the incidence of AEs, and secondary measures were type of injury, severity of harm, preventability of AEs, estimated healthcare cost of AEs and incidence of AEs in patients cared for in another type of unit than the one specialised for their medical needs (‘off-site’).ResultsIn a review of 64 917 admissions, the average AE rates in 2014 (11.6%), 2015 (10.9%) and 2016 (11.4%) were significantly lower than in 2013 (13.1%). The decrease in the AE rates was seen in different age groups, in both genders and for preventable and non-preventable AEs. The decrease comprised only the least severe AEs. The types of AEs that decreased were hospital-acquired infections, urinary bladder distention and compromised vital signs. Patients cared for ‘off-site’ had 84% more preventable AEs than patients cared for in the appropriate units. The cost of increased length of stay associated with preventable AEs corresponded to 13%–14% of the total cost of somatic hospital care in Sweden.ConclusionsThe rate of AEs in Swedish somatic hospitals has decreased from 2013 to 2016. Retrospective record review can be used to monitor patient safety over time, to assess the effects of national patient safety interventions and analyse challenges to patient safety such as the increasing care of patients ‘off-site’. It was found that the economic burden of preventable AEs is high.
Association between asthma and lung function in adolescents born very preterm: results of the EPIPAGE cohort study
Authors: Hadchouel Alice , Rousseau Jessica , Rozé Jean-Christophe , Arnaud Catherine , Bellino Adèle , Couderc Laure , Marret Stéphane , Mittaine Marie , Pinquier Didier , Verstraete Marie , Ancel Pierre-Yves , Delacourt Christophe 
Published: March 2018

Prematurity and bronchopulmonary dysplasia (BPD) affect long-term lung function. We studied the respiratory outcome of adolescents born very preterm and controls from the Etude EPIdémiologique sur les Petits Ages Gestationnels cohort and analysed their current lung function in relation to asthma symptoms (categorised in three age groups) from birth. In models including BPD, asthma at each age and confounding factors in the preterm group, BPD and preschool wheeze were the only independent variables associated with FEV1. Preschool wheeze is an independent factor associated with FEV1 impairment in adolescents born very preterm. These results highlight the need for optimal management of early respiratory symptoms in preterm-born infants.Trial registration numberResults, NCT01424553.
Tumor-Derived GM-CSF Promotes Granulocyte Immunosuppression in Mesothelioma Patients
Authors: Khanna Swati , Graef Suzanne , Mussai Francis , Thomas Anish , Wali Neha , Yenidunya Bahar Guliz , Yuan Constance , Morrow Betsy , Zhang Jingli , Korangy Firouzeh , Greten Tim F. , Steinberg Seth M. , Stetler-Stevenson Maryalice , Middleton Gary , De Santo Carmela , Hassan Raffit 
Published: March 2018

Abstract
Purpose: The cross-talk between tumor cells, myeloid cells, and T cells can play a critical role in tumor pathogenesis and response to immunotherapies. Although the etiology of mesothelioma is well understood, the impact of mesothelioma tumor cells on the surrounding immune microenvironment is less well studied. In this study, the effect of the mesothelioma tumor microenvironment on circulating and infiltrating granulocytes and T cells is investigated.
Experimental Design: Tumor tissues and peripheral blood from mesothelioma patients were evaluated for presence of granulocytes, which were then tested for their T-cell suppression potential. Different cocultures of granulocytes and/or mesothelioma tumor cells and/or T cells were set up to identify the mechanism of T-cell inhibition.
Results: Analysis of human tumors showed that the mesothelioma microenvironment is enriched in infiltrating granulocytes, which inhibit T-cell proliferation and activation. Characterization of the whole blood at diagnosis identified similar, circulating, immunosuppressive CD11b+CD15+HLADR− granulocytes at increased frequency compared with healthy controls. Culture of healthy-donor granulocytes with human mesothelioma cells showed that GM-CSF upregulates NOX2 expression and the release of reactive oxygen species (ROS) from granulocytes, resulting in T-cell suppression. Immunohistochemistry and transcriptomic analysis revealed that a majority of mesothelioma tumors express GM-CSF and that higher GM-CSF expression correlated with clinical progression. Blockade of GM-CSF with neutralizing antibody, or ROS inhibition, restored T-cell proliferation, suggesting that targeting of GM-CSF could be of therapeutic benefit in these patients.
Conclusions: Our study presents the mechanism behind the cross-talk between mesothelioma tumors and the immune microenvironment and indicates that targeting GM-CSF could be a novel treatment strategy to augment immunotherapy in patients with mesothelioma. Clin Cancer Res; 24(12); 2859–72. ©2018 AACR.