bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variability of tissue factor‐activated thromboelastography and whole blood impedance platelet aggregometry in healthy dogs
Authors: Shropshire Sarah B. , Olver Christine S. , Lappin Michael R. 
Published: June 2018

AbstractObjectiveTo assess interindividual (CVG) and intraindividual (CVI) variability over time for results of thromboelastography (TEG) and whole‐blood impedance platelet aggregometry in healthy dogs.AnimalsSix healthy Beagle dogs.Measurements and Main ResultsTissue factor (TF)‐activated TEG and adenosine diphosphate (ADP) and arachidonic acid (AA)‐induced whole blood impedance platelet aggregometry were performed at 3 different time points (days 1, 4, and 6). In addition, platelet count, hematocrit, and plasma fibrinogen concentrations were recorded each study day. Activated partial thromboplastin time, one‐stage prothrombin time, antithrombin activity, and D‐dimer concentrations were measured on the first day of the study. For TEG, the variables reaction time (R), clotting time (K), rate of clot formation (α), and maximum amplitude (MA) were recorded. For platelet aggregometry, the areas under the curve for ADP (AUCADP)‐ and AA (AUCAA)‐induced aggregation were measured. The CVI was lower than the CVG over time for MA, AUCADP, and AUCAA; however, the CVI was higher than the CVG for the TEG variables R, K, and α. There were no statistical differences in the platelet count, hematocrit, and fibrinogen measurements over time.ConclusionsIn healthy dogs, a subject‐based reference interval for ADP‐ and AA‐induced platelet aggregometry and the TEG variable MA provide a more sensitive method to detect changes. However, due to the high CVI, population‐based reference intervals may be more appropriate for interpretation of the TEG variables R, K, and α.
The influence of sex and neonatal stress on medullary microglia in rat pups
Authors: Baldy Cécile , Fournier Stéphanie , Boisjoly‐Villeneuve Samuel , Tremblay Marie‐Ève , Kinkead Richard 
Published: June 2018

New FindingsWhat is the central question of the study?Does neonatal stress, in the form of neonatal maternal separation, influence the maturation of microglial density, morphology and neuronal signalling in medullary regions regulating cardiorespiratory function in rat pups?What is the main finding and its importance?Using Iba‐1 immunohistochemistry, we show that neonatal maternal separation augments microglial density and the proportion of cells with an amoeboid morphology in the medulla. Although the current understanding of the effect of early life stress on medullary development is relatively limited, these data show that within this area, microglia are affected by neonatal stress. Microglia could therefore be important effectors in cardiorespiratory disorders resulting from maternal separation.AbstractNeonatal stress has wide‐ranging consequences for the developing brain, including the medullary cardiorespiratory network. In rat pups, the reflexive cardiorespiratory inhibition triggered by the presence of liquids near the larynx is augmented by neonatal maternal separation (NMS), especially in males. Sex‐specific enhancement of synaptic connectivity by NMS might explain this cardiorespiratory dysfunction. Microglia influence the formation, maturation, activity and elimination of developing synapses, but their role in the wiring of medullary networks is unknown. Owing to their sensitivity to sex hormones and stress hormones, microglial dysfunction could contribute to the abnormal cardiorespiratory phenotype observed in NMS pups. Here, we first used ionized calcium‐binding adapter molecule‐1 (Iba‐1) immunolabelling to compare the density and morphology of microglia in the medulla of maleversusfemale rat pups (14–15 days old) that were either undisturbed or subjected to NMS (3 h day−1; postnatal days 3–12). Neonatal maternal separation augmented the density of Iba‐1+cells (caudal region of the NTS), increased the size of the soma and reduced the arborization area (especially in the dorsal motor nucleus of the vagus). Sex‐based differences were not observed. Given that the actions of microglia are regulated by neuronal fractalkine (CX3CL1), we then used western blot analysis to compare the expression of CX3CL1and its microglial receptor (CX3CR1) in medullary homogenates from control and NMS pups. Although CX3CR1expression was 59% greater in malesversusfemales, NMS had no effect on CX3CL1/CX3CR1signalling. Given that an amoeboid morphology reflects an immature phenotype in developing microglia, NMS could interfere with synaptic pruning via a different mechanism.
Hypoxic pulmonary vasoconstriction in isolated mouse pulmonary arterial vessels
Authors: Strielkov Ievgen , Krause Nicole Catherine , Sommer Natascha , Schermuly Ralph Theo , Ghofrani Hossein Ardeschir , Grimminger Friedrich , Gudermann Thomas , Dietrich Alexander , Weissmann Norbert 
Published: June 2018

New Findings
What is the central question of this study?
Hypoxic pulmonary vasoconstriction has never been characterized in isolated mouse pulmonary arteries of different generations in detail.

What is the main finding and its importance?
We found that only small intrapulmonary arteries (80–200 μm in diameter) exhibit hypoxic pulmonary vasoconstriction. The observed response was sustained, significantly potentiated by depolarization‐induced preconstriction and not dependent on the endothelium or TRPC6 channels.

AbstractHypoxic pulmonary vasoconstriction (HPV) is a physiological response of pulmonary arteries, which adapts lung perfusion to regional ventilation. The properties of HPV vary significantly between animal species. Despite extensive use of mouse models in studies of HPV, this physiological response has never been characterized in isolated mouse pulmonary arteries in detail. Using wire myography, we investigated the effect of 80 min exposure to hypoxia on the tone in mouse pulmonary arteries of different generations in the presence and absence of preconstriction. Hypoxia induced a sustained relaxation in non‐preconstricted extrapulmonary arteries (500–700 μm in diameter), but not in the presence of KCl‐induced preconstriction. Large intrapulmonary arteries (450–650 μm in diameter) did not exhibit a significant response to the hypoxic challenge. In contrast, in small intrapulmonary arteries (80–200 μm in diameter), hypoxia elicited a slowly developing sustained constriction, which was independent of the endothelium. The response was significantly potentiated in arteries preconstricted with KCl, but not with U46619. Hypoxic pulmonary vasoconstriction was not altered in pulmonary arteries of TRPC6‐deficient mice, which suggests that this response corresponds to the sustained phase of biphasic HPV observed earlier in isolated, buffer‐perfused and ventilated mouse lungs. In conclusion, we have established a protocol that allows the study of sustained HPV in isolated mouse pulmonary arteries. The data obtained might be useful for future studies of the mechanisms of HPV in mice.
Reduced blood volume decreases cerebral blood flow in preterm piglets
Authors: Eiby Yvonne A. , Shrimpton Nicole Y. , Wright Ian M. R. , Lumbers Eugenie R. , Colditz Paul B. , Duncombe Greg J. , Lingwood Barbara E. 
Published: June 2018

Key points
Preterm infants often have poor cardiovascular function that is associated with adverse neurodevelopmental outcomes.
Preterm infants may be vulnerable to hypovolaemia due to excessive vasodilatation and leaky capillaries.
Following reduction in blood volume, cardiac output and mean arterial pressure were reduced to the same extent in term and preterm piglets.
Cerebral blood flow was maintained following blood volume reduction in term but not in preterm piglets.
Effective detection and treatment of functional hypovolaemia may reduce the risk of brain injury in preterm infants.
AbstractPreterm infants often have impaired cardiovascular function that may contribute to poor neurodevelopmental outcomes. The study aimed to determine the effects of reduced blood volume on cardiovascular function, including cerebral blood flow, in preterm and term piglets. In preterm (97/115 days) and term piglets, up to 10% of the estimated blood volume was removed. Removal of blood was stopped if MAP dropped below 20 mmHg. Heart rate, cardiac contractility and relaxation, cardiac output, mean arterial pressure (MAP), and cerebral blood flow were measured at baseline and again after blood volume reduction. The volume of blood removed was less in preterm piglets than in term piglets (5.1 ± 1.8 vs. 7.7 ± 0.9 mL kg−1, mean ± SD, P < 0.001). Cardiac output and MAP decreased to the same extent in term and preterm piglets. Cerebral blood flow decreased in preterm but not term piglets and cerebral vascular conductance increased in term piglets only. Compensatory responses to maintain cerebral blood flow after blood volume reduction are active in term piglets but not in preterm piglets. As a result, even a small reduction in blood volume, or an increase in the capacity of the circulatory system leading to functional hypovolaemia, may lead to a significant reduction in cerebral blood flow and contribute to brain injury in preterm neonates.
Sodium nitroprusside dilates cerebral vessels and enhances internal carotid artery flow in young men
Authors: Olesen Niels D. , Fischer Mads , Secher Niels H. 
Published: June 2018

Key points
Sodium nitroprusside lowers blood pressure by vasodilatation but is reported to reduce cerebral blood flow.
In healthy young men sodium nitroprusside reduced blood pressure, total peripheral resistance, and arterial CO2 tension and yet cerebral blood flow was maintained, with an increase in internal carotid artery blood flow and cerebrovascular conductance.
Sodium nitroprusside induces both systemic and cerebral vasodilatation affecting internal carotid artery more than vertebral artery flow.
AbstractCerebral autoregulation maintains cerebral blood flow (CBF) despite marked changes in mean arterial pressure (MAP). Sodium nitroprusside (SNP) reduces blood pressure by vasodilatation but is reported to lower CBF, probably by a reduction in its perfusion pressure. We evaluated the influence of SNP on CBF and aimed for a 20% and then 40% reduction in MAP, while keeping MAP ≥ 50 mmHg, to challenge cerebral autoregulation. In 19 healthy men (age 24 ± 4 years; mean ± SD) duplex ultrasound determined right internal carotid (ICA) and vertebral artery (VA) blood flow. The SNP reduced MAP (from 83 ± 8 to 69 ± 8 and 58 ± 4 mmHg; both P < 0.0001), total peripheral resistance, and arterial CO2 tension (; 41 ± 3 vs. 39 ± 3 and 37 ± 4 mmHg; both P < 0.01). Yet ICA flow increased with the moderate reduction in MAP but returned to the baseline value with the large reduction in MAP (336 ± 66 vs. 365 ± 69; P = 0.013 and 349 ± 82 ml min–1; n.s.), while VA flow (114 ± 34 vs. 112 ± 38 and 110 ± 42 ml min–1; both n.s.) and CBF ((ICA + VA flow) × 2; 899 ± 135 vs. 962 ± 127 and 918 ± 197 ml min–1; both n.s.) were maintained with increased cerebrovascular conductance. In conclusion, CBF is maintained during SNP‐induced reduction in MAP despite reduced and the results indicate that SNP dilates cerebral vessels and increases ICA flow.
Classification of GABAergic neuron subtypes from the globus pallidus using wild‐type and transgenic mice
Authors: Abrahao Karina P. , Lovinger David M. 
Published: June 2018

Key points
Classifying different subtypes of neurons in deep brain structures is a challenge and is crucial to better understand brain function.
Understanding the diversity of neurons in the globus pallidus (GP), a brain region positioned to influence afferent and efferent information processing within basal ganglia, could help to explain a variety of brain functions.
We present a classification of neurons from the GP using electrophysiological data from wild‐type mice and confirmation using transgenic mice.
This work will help researchers to identify specific neuronal subsets in the GP of wild‐type mice when transgenic mice with labelled neurons are lacking.
AbstractClassification of the extensive neuronal diversity in the brain is fundamental for neuroscience. The globus pallidus external segment (GPe), also referred to as the globus pallidus in rodents, is a large nucleus located in the core of the basal ganglia whose circuitry is implicated in action control, decision‐making and reward. Although considerable progress has been made in characterizing different GPe neuronal subtypes, no work has directly attempted to characterize these neurons in non‐transgenic mice. Here, we provide data showing the degree of overlap in expression of neuronal PAS domain protein (Npas1), LIM homeobox 6 (Lhx6), parvalbumin (PV) and transcription factor FoxP2 biomarkers in mouse GPe neurons. We used an unbiased statistical method to classify neurons based on electrophysiological properties from nearly 200 neurons from C57BL/6J mice. In addition, we examined the subregion distribution of the neuronal subtypes. Cluster analysis using firing rate and hyperpolarization‐induced membrane potential sag variables revealed three distinct neuronal clusters: type 1, characterized by low firing rate and small sag potential; type 2, with low firing rate and larger sag potential; and type 3, with high firing rate and small sag potential. We used other electrophysiological variables and data from marker‐expressing neurons to evaluate the clusters. We propose that the GPe GABAergic neurons should be classified into three subgroups: arkypallidal, low‐firing prototypical and high‐firing prototypical neurons. This work will help researchers identify GPe neuron subtypes when transgenic mice with labelled neurons cannot be used.
Antimicrobial Resistance inPasteurellaceaeof Veterinary Origin
Authors: Michael Geovana B. , Bossé Janine T. , Schwarz Stefan 
Published: June 2018

ABSTRACTMembers of the highly heterogeneous familyPasteurellaceaecause a wide variety of diseases in humans and animals. Antimicrobial agents are the most powerful tools to control such infections. However, the acquisition of resistance genes, as well as the development of resistance-mediating mutations, significantly reduces the efficacy of the antimicrobial agents. This article gives a brief description of the role of selected members of the familyPasteurellaceaein animal infections and of the most recent data on the susceptibility status of such members. Moreover, a review of the current knowledge of the genetic basis of resistance to antimicrobial agents is included, with particular reference to resistance to tetracyclines, β-lactam antibiotics, aminoglycosides/aminocyclitols, folate pathway inhibitors, macrolides, lincosamides, phenicols, and quinolones. This article focusses on the genera of veterinary importance for which sufficient data on antimicrobial susceptibility and the detection of resistance genes are currently available (Pasteurella,Mannheimia,Actinobacillus,Haemophilus, andHistophilus). Additionally, the role of plasmids, transposons, and integrative and conjugative elements in the spread of the resistance genes within and beyond the aforementioned genera is highlighted to provide insight into horizontal dissemination, coselection, and persistence of antimicrobial resistance genes. The article discusses the acquisition of diverse resistance genes by the selectedPasteurellaceaemembers from other Gram-negative or maybe even Gram-positive bacteria. Although the susceptibility status of these members still looks rather favorable, monitoring of their antimicrobial susceptibility is required for early detection of changes in the susceptibility status and the newly acquired/developed resistance mechanisms.
Antimicrobial Stewardship in Veterinary Medicine
Authors: Lloyd David H. , Page Stephen W. 
Published: June 2018

ABSTRACT
While antimicrobial resistance is already a public health crisis in human medicine, therapeutic failure in veterinary medicine due to antimicrobial resistance remains relatively uncommon. However, there are many pathways by which antimicrobial resistance determinants can travel between animals and humans: by close contact, through the food chain, or indirectly via the environment. Antimicrobial stewardship describes measures that can help mitigate the public health crisis and preserve the effectiveness of available antimicrobial agents. Antimicrobial stewardship programs have been principally developed, implemented, and studied in human hospitals but are beginning to be adapted for other applications in human medicine. Key learning from the experiences of antimicrobial stewardship programs in human medicine are summarized in this article—guiding the development of a stewardship framework suitable for adaptation and use in both companion animal and livestock practice. The antimicrobial stewardship program for veterinary use integrates infection prevention and control together with approaches emphasizing avoidance of antimicrobial agents. The 5R framework of continuous improvement that is described recognizes the importance of executive support; highly motivated organizations and teams (responsibility); the need to review the starting position, set objectives, and determine means of measuring progress and success; and a critical focus on reducing, replacing, and refining the use of antimicrobial agents. Significant issues that are currently the focus of intensive research include improved detection and diagnosis of infections, refined dosing regimens that are simultaneously effective while not selecting resistance, searches for alternatives to antimicrobial agents, and development of improved vaccines to enhance immunity and reduce disease.
Source Attribution and Risk Assessment of Antimicrobial Resistance
Authors: Pires Sara M. , Duarte Ana Sofia , Hald Tine 
Published: June 2018

ABSTRACTSource attribution and microbial risk assessment methods have been widely applied for the control of several foodborne pathogens worldwide by identifying (i) the most important pathogen sources and (ii) the risk represented by specific foods and the critical points in these foods’ production chains for microbial control. Such evidence has proved crucial for risk managers to identify and prioritize effective food safety and public health strategies. In the context of antimicrobial resistance (AMR) from livestock and pets, the utility of these methods is recognized, but a number of challenges have largely prevented their application and routine use. One key challenge has been to define the hazard in question: Is it the antimicrobial drug use in animals, the antimicrobial-resistant bacteria in animals and foods, or the antimicrobial resistance genes that can be transferred between commensal and pathogenic bacteria in the animal or human gut or in the environment? Other important limitations include the lack of occurrence and transmission data and the lack of evidence to inform dose-response relationships. We present the main principles, available methods, strengths, and weaknesses of source attribution and risk assessment methods, discuss their utility to identify sources and estimate risks of AMR from livestock and pets, and provide an overview of conducted studies. In addition, we discuss remaining challenges and current and future opportunities to improve methods and knowledge of the sources and transmission routes of AMR from animals through food, direct contact, or the environment, including improvements in surveillance and developments in genotypic typing methods.
Epitranscriptomics: RNA Modifications in Bacteria and Archaea
Authors: Höfer Katharina , Jäschke Andres 
Published: June 2018

ABSTRACT
The increasingly complex functionality of RNA is contrasted by its simple chemical composition. RNA is generally built from only four different nucleotides (adenine, guanine, cytosine, and uracil). To date, >160 chemical modifications are known to decorate RNA molecules and thereby alter their function or stability. Many RNA modifications are conserved throughout bacteria, archaea, and eukaryotes, while some are unique to each branch of life. Most known modifications occur at internal positions, while there is limited diversity at the termini. The dynamic nature of RNA modifications and newly discovered regulatory functions of some of these RNA modifications gave birth to a new field, now often referred to as “epitranscriptomics.” This review highlights the major developments in this field and summarizes detection principles for internal as well as 5′-terminal mRNA modifications in prokaryotes and archaea to investigate their biological significance.
Muscular weakness in adolescence is associated with disability 30 years later: a population-based cohort study of 1.2 million men
Authors: Henriksson Hanna , Henriksson Pontus , Tynelius Per , Ortega Francisco B 
Published: June 2018

ObjectiveTo investigate the associations of muscular strength in adolescence with later disability pension (DP), across different body mass index (BMI) categories and in combination with aerobic fitness.MethodThis prospective cohort study consisted of males aged 16–19 years, recruited from the Swedish military conscription register between 1969 and 1994. A total of 1 212 503 adolescents met all the inclusion criteria and were therefore included in the analyses. Knee extension, handgrip and elbow flexion strength and aerobic fitness (bicycle ergometer test) were measured during conscription. Causes of DP were retrieved from the Social Insurance Office between years 1971 and 2012 (average follow-up time: 29.6 years).ResultsKnee extension strength in adolescence was inversely associated with men’s risk of obtaining DP due to all causes (HR 1.40, 95% CI 1.36 to 1.44 for lowest vs highest strength quintile). Thus, muscular weakness was associated with DP. The risk associated with low muscular strength differed between specific causes of DP and the strongest associations were found for psychiatric, nervous system and other causes (HRs between 1.47 and 1.90 for lowest vs highest quintile). Being strong was associated with lower DP risk across BMI categories and being unfit, weak and obese was associated with the highest DP risk (HR 3.70, 95% CI 2.99 to 4.58).ConclusionThere was a strong association between muscular weakness and disability. A combination of muscular weakness and low aerobic fitness was an especially important risk factor for disability. This adds weight to call for muscular strength and fitness enhancing exercise for adolescents in all BMI categories.