bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of α1A‐adrenoceptors desensitizes the rat aorta response to phenylephrine through a neuronal NOS pathway, a mechanism lost with ageing
Authors: Arce Cristina , Vicente Diana , Segura Vanessa , Flacco Nicla , Montó Fermi , Almenar Luis , Agüero Jaime , Rueda Joaquín , Jiménez‐Altayó Francesc , Vila Elisabet , Noguera Maria Antonia , D'Ocon Pilar , Ivorra Maria Dolores 
Published: March 2017

Background and PurposeA NO‐mediated desensitization of vasoconstrictor responses evoked by stimulation of α1‐adrenoceptors has been reported in different vessels. We investigated the involvement of each α1‐adrenoceptor subtype and constitutive NOS isoforms and the influence of ageing and hypertension on this process.Experimental ApproachWistar and spontaneously hypertensive rats (SHR), 16, 32, 52 and 72 weeks‐old, were used to evaluate the desensitization process. Expression of α1‐adrenoceptor subtypes, endothelial NOS (eNOS) and neuronal NOS (nNOS) were determined in rat aorta and left ventricle (LV). Expression levels were also evaluated in LV of a group of heart failure patients with a wide age range.Key ResultsRepeated application of phenylephrine decreased subsequent α1‐adrenoceptor‐mediated vasoconstriction by increasing nNOS protein expression in aorta, but not in tail or mesenteric resistance arteries, where mRNA levels of nNOS were undetectable. This desensitization process disappeared in the absence of endothelium or in the presence of L‐NAME (100 μM), nNOS inhibitors, SMTC (1 μM) and TRIM (100 μM), and 5‐methylurapidil (100 nM, α1A‐antagonist), but not BMY7378 (10 nM, α1D‐antagonist). The α1A/nNOS‐mediated desensitization was absent in aged SHR and Wistar animals, where the expression of α1A‐adrenoceptors was reduced in aorta and LV. In human LV, a negative correlation was found between age and α1A‐adrenoceptor expression.Conclusions and ImplicationsThe α1A‐adrenoceptor subtype, through endothelial nNOS‐derived NO, may act as a physiological ‘brake’ against the detrimental effects of excessive α1‐adrenoceptor‐mediated vasoconstriction. Reduced α1A‐adrenoceptor‐ and nNOS‐mediated desensitization in aged patients could be involved in the age‐dependent elevation of adrenergic activity.
Palmoplantar pustulosis and pustulotic arthro‐osteitis treatment with potassium iodide and tetracycline, a novel remedy with an old drug: a review of 25 patients
Authors: Hayashi Shujiro , Shimaoka Yayoi , Hamasaki Yoichiro , Hatamochi Atsushi 
Published: March 2017

AbstractBackgroundThe use of potassium iodide (KI) to treat palmoplantar pustulosis (PPP) and pustulotic arthro‐osteitis (PAO) has not previously been reported. Here, we report the first successful treatment of PPP and PAO with KI.Patient and MethodsAmong 25 patients with PPP, seven had an associated PAO. All patients were administered 900 mg KI three times per day for 3 months. Overall, 12 patients received this medical treatment for the first time or had >6 months interval since the last therapy for PPP. The other 13 patients who were nonresponsive to tetracycline for >3 months prior to KI treatment were treated with a combination of KI and tetracycline. All seven patients with PAO were included in the tetracycline and KI‐treated group.ResultsMore than 70% of patients demonstrated complete clearance or ≥50% improvement in palmoplantar pustular psoriasis area and severity index (PPPASI) from baseline. In the group with <50% improvement in PPPASI from baseline, all except one patient were smokers. In the KI with tetracycline treatment group, approximately 80% demonstrated improvement. At the end of 3 months, there was remission of arthralgia in five out of seven PPP patients with PAO.ConclusionsTreatment with KI and/or its combination with tetracycline may be a useful treatment for PPP/PAO. Smoking may affect the effectiveness of these treatment modalities.
Atomic‐scale microstructure of Hf2Al4C5 ceramic synthesized by spark plasma sintering
Authors: Song Kepeng , Zhang Hui , Du Kui , Qi Dongqing , Chen Houwen , Wang Xiaohui , Nie Jian‐Feng , Ye Hengqiang 
Published: March 2017

AbstractA layered ternary carbide phase, Hf2Al4C5, was successfully synthesized by spark plasma sintering method. Detailed (atomic‐scale) microstructure of the ternary carbide was investigated by aberration‐corrected scanning transmission electron microscopy and atomic‐resolution energy dispersive X‐ray spectroscopy. Hf2Al4C5 crystal grains have elongated morphologies and are characterized with a high density of stacking faults with the insertion of additional (Al4C3) or (HfC) units. Periodic stacking of Hf2Al4C5 and HfAl4C4 units along the [0001] direction is frequently observed in the Hf2Al4C5 crystal, and it leads to the formation of Hf4Al12C13, which consists of 2/3 Hf2Al4C5 unit cell and 1/2 HfAl4C4 unit cell. In addition, Z‐shaped planar defects are observed in Hf2Al4C5 grains, and the formation mechanism of the Z‐shaped defects was proposed as blocking effects of the Hf diffusion in Al4C3 by pre‐existing {1‐101} pyramidal stacking faults in Al4C3.
Microstructure and mechanical properties of B4C–TiB2–SiC composites toughened by composite structural toughening phases
Authors: Zhang Xiaorong , Zhang Zhixiao , Wang Weimin , Shan Junhong , Che Hongwei , Mu Jingbo , Wang Guangsuo 
Published: March 2017

AbstractB4C–TiB2–SiC composites toughened by composite structural toughening phases, which are the units of (TiB2–SiC) composite, were fabricated through reactive hot pressing with B4C, TiC, and Si as raw materials. The units of (TiB2–SiC) composite with the size of 10‐20 μm are composed of interlocking TiB2 and SiC with the size of 1‐5 μm. The addition of TiC and Si can effectively promote the sintering of B4C ceramics. The relative densities of all the B4C composites with different contents of TiB2 and SiC are close to completely dense (98.9%‐99.4%), thereby resulting in superior hardness (33.1‐36.2 GPa). With the increase in the content of TiB2 and SiC, the already improved fracture toughness of the B4C composite continuously increases (5.3‐6.5 MPa·m1/2), but the flexure strength initially increases and then decreases. When cracks cross the units of the (TiB2–SiC) composite, the cracks deflect along the interior boundary of TiB2 and SiC inside the units. As the crack growth path is lengthened, the crack propagation direction is changed, thereby consuming more crack extension energy. The cumulative contributions improve the fracture toughness of the B4C composite. Therefore, the composite structural toughening units of the (TiB2–SiC) composite play an important role in reinforcing the fracture toughness of the composites.
Phase 2 of CATALISE: a multinational and multidisciplinary Delphi consensus study of problems with language development: Terminology
Authors: Bishop Dorothy V.M. , Snowling Margaret J. , Thompson Paul A. , Greenhalgh Trisha ,   and the CATALISE‐2 consortium
Published: March 2017

BackgroundLack of agreement about criteria and terminology for children's language problems affects access to services as well as hindering research and practice. We report the second phase of a study using an online Delphi method to address these issues. In the first phase, we focused on criteria for language disorder. Here we consider terminology.MethodsThe Delphi method is an iterative process in which an initial set of statements is rated by a panel of experts, who then have the opportunity to view anonymised ratings from other panel members. On this basis they can either revise their views or make a case for their position. The statements are then revised based on panel feedback, and again rated by and commented on by the panel. In this study, feedback from a second round was used to prepare a final set of statements in narrative form. The panel included 57 individuals representing a range of professions and nationalities.ResultsWe achieved at least 78% agreement for 19 of 21 statements within two rounds of ratings. These were collapsed into 12 statements for the final consensus reported here. The term ‘Language Disorder’ is recommended to refer to a profile of difficulties that causes functional impairment in everyday life and is associated with poor prognosis. The term, ‘Developmental Language Disorder’ (DLD) was endorsed for use when the language disorder was not associated with a known biomedical aetiology. It was also agreed that (a) presence of risk factors (neurobiological or environmental) does not preclude a diagnosis of DLD, (b) DLD can co‐occur with other neurodevelopmental disorders (e.g. ADHD) and (c) DLD does not require a mismatch between verbal and nonverbal ability.ConclusionsThis Delphi exercise highlights reasons for disagreements about terminology for language disorders and proposes standard definitions and nomenclature.
Knowledge, perceptions and attitude of a community living around a colony of straw‐coloured fruit bats (Eidolon helvum) in Ghana after Ebola virus disease outbreak in West Africa
Authors: Gbogbo F. , Kyei M. O. 
Published: March 2017

SummaryA large population of straw‐coloured fruit bats (Eidolon helvum) colonizes a prime area in the city of Accra where several public amenities are located. Although the colony is positive to several zoonotic viruses including the Ebola virus, there is limited information on the social dimensions of the existence of the bats. As a step towards effective response to health risk and conservation of the bats, this study assessed the knowledge and attitude of the community living around the bats and determined their level of environmental and public health consciousness. The community generally lacks interest in bat bushmeat consumption but had low knowledge and disease risk perception of the bats. Despite major campaigns during the recent Ebola outbreak in West Africa, elements of risky behaviour including disbelief and disregard for some preventive measures and lack of interest in post‐bat exposure prophylaxis were recorded among a limited proportion of the community. There was the need to focus public health education on the community and possibly others that may have E. helvum colonies in West Africa.
Evaluation of GenoType NTM-DR Assay for Identification of Mycobacterium chimaera
Authors: Mok Simone , Rogers Thomas R. , Fitzgibbon Margaret 
Published: March 2017

ABSTRACT

Identification of species within the
Mycobacterium avium
complex (MAC) is difficult, and most current diagnostic laboratory tests cannot distinguish between species included in the complex. Differentiation of species within the MAC is important, as
Mycobacterium chimaera
has recently emerged as a major cause of invasive cardiovascular infections following open heart surgery. A new commercial diagnostic assay, GenoType NTM-DR ver. 1.0, is intended to differentiate between three species within the MAC, namely,
Mycobacterium avium
,
Mycobacterium intracellulare
, and
Mycobacterium chimaera
. In this study, we investigated an archival collection of 173 MAC isolates using 16S rRNA and 16S-23S internal transcribed spacer (ITS) gene sequencing, and GenoType NTM-DR was evaluated for identifying
M. chimaera
and other species belonging to the MAC. Species identification of 157/173 (91%) isolates with the GenoType NTM-DR assay was in agreement with 16S rRNA and 16S-23S ITS gene sequencing results. Misidentification occurred with 16 isolates which belonged to four species included in the MAC that are rarely encountered in clinical specimens. Despite some limitations of this assay, GenoType NTM-DR had 100% specificity for identifying
M. chimaera
. This novel assay will enable diagnostic laboratories to differentiate species belonging to the
Mycobacterium avium
complex and to accurately identify
M. chimaera
. It can produce rapid results and is also more cost efficient than gene sequencing methods.
MicroRNA miR-27 Inhibits Adenovirus Infection by Suppressing the Expression of SNAP25 and TXN2
Authors: Machitani Mitsuhiro , Sakurai Fuminori , Wakabayashi Keisaku , Nakatani Kosuke , Tachibana Masashi , Mizuguchi Hiroyuki 
Published: March 2017

ABSTRACT

Recent studies have reported that host microRNAs (miRNAs) regulate infections by several types of viruses via various mechanisms and that inhibition of the miRNA processing factors enhances or prevents viral infection. However, it has not been clarified whether these effects of miRNAs extend to adenovirus (Ad) infection. Here we show that miR-27a and -b efficiently inhibit infection with an Ad via the downregulation of SNAP25 and TXN2, which are members of the SNARE proteins and the thioredoxin family, respectively. Approximately 80% reductions in Ad genomic copy number were found in cells transfected with miR-27a/b mimics, whereas there were approximately 2.5- to 5-fold larger copy numbers of the Ad genome following transfection with miR-27a/b inhibitors. Microarray gene expression analysis and
in silico
analysis demonstrated that SNAP25 and TXN2 are target genes of miR-27a/b. A reporter assay using plasmids containing the 3′ untranslated regions of the SNAP25 and TXN2 genes showed that miR-27a/b directly suppressed SNAP25 and TXN2 expression through posttranscriptional gene silencing. Knockdown of SNAP25 led to a significant inhibition of Ad entry into cells. Knockdown of TXN2 induced cell cycle arrest at G
1
phase, leading to a reduction in Ad replication. In addition, overexpression of Ad-encoded small noncoding RNAs (VA-RNAs) restored the miR-27a/b-mediated reduction in infection level with a VA-RNA-lacking Ad mutant due to the VA-RNA-mediated inhibition of miR-27a/b expression. These results indicate that miR-27a and -b suppress SNAP25 and TXN2 expression via posttranscriptional gene silencing, leading to efficient suppression of Ad infection.

IMPORTANCE
Adenovirus (Ad) is widely used as a platform for replication-incompetent Ad vectors (Adv) and replication-competent oncolytic Ad (OAd) in gene therapy and virotherapy. Regulation of Ad infection is highly important for efficient gene therapies using both Adv and OAd. In this study, we demonstrate that miR-27a and -b, which are widely expressed in host cells, suppress SNAP25 and TXN2 expression through posttranscriptional gene silencing. Suppression of SNAP25 and TXN2 expression leads to inhibition of Ad entry into cells and to cell cycle arrest, respectively, leading to efficient suppression of Ad infection. Our findings provide important clues to the improvement of gene therapies using both Adv and OAd.
Implementing a self-management strategy in inflammatory bowel disease (IBD): patient perceptions, clinical outcomes and the impact on service
Authors: Squires Seth Ian , Boal Allan John , Lamont Selina , Naismith Graham D 
Published: March 2017

IntroductionPatient self-management and its service integration is not a new concept but it may be a key component in the long-term sustainability of inflammatory bowel disease (IBD) service provision, when considering growing disease prevalence and limited resources.MethodsThe IBD team at the Royal Alexandra and Vale of Leven Hospitals in the Clyde Valley region developed a self-management tool, called the ‘flare card’. Patients were asked to complete a questionnaire which reflected their opinion on its viability as a self-management intervention. In addition, its utility in terms of service use over a 10-month period in 2016 was compared with a similar cohort of patients over 10 months in 2015.ResultsPatients overall felt that the ‘flare card’ was a viable self-management tool. Positive feedback identified that the intervention could help them aid control over their IBD, improve medication adherence, reduce symptoms and reflected a feeling of patient-centred IBD care. The comparison between 2015 and 2016 service use revealed a significant reduction in IBD and non-IBD service usage, Steroid prescribing and unscheduled IBD care in the flare card supported cohort.ConclusionsIBD services must continue to adapt to changes within the National Health Service bearing in mind long-term sustainability and continued care provision. The ‘flare card’ goes further in an attempt to optimise Crohn's disease and ulcerative colitis management by harmonising clinician evaluation and patient's self-initiation of therapy and investigation.
Increased cerebral blood volume pulsatility during head-down tilt with elevated carbon dioxide: the SPACECOT Study
Authors: Strangman Gary E. , Zhang Quan , Marshall-Goebel Karina , Mulder Edwin , Stevens Brian , Clark Jonathan B. , Bershad Eric M. 
Published: March 2017

Astronauts aboard the International Space Station (ISS) have exhibited hyperopic shifts, posterior eye globe flattening, dilated optic nerve sheaths, and even optic disk swelling from spaceflight. Elevated intracranial pressure (ICP) consequent to cephalad fluid shifts is commonly hypothesized as contributing to these ocular changes. Head-down tilt (HDT) is frequently utilized as an Earth-based analog to study similar fluid shifts. Sealed environments like the ISS also exhibit elevated CO2, a potent arteriolar vasodilator that could further affect cerebral blood volume (CBV) and cerebral blood flow, intracranial compliance, and ICP. A collaborative pilot study between the National Space Biomedical Research Institute and the German Aerospace Center tested the hypotheses that 1) HDT and elevated CO2 physiologically interact and 2) cerebrovascular pulsatility is related to HDT and/or elevated CO2. In a double-blind crossover study ( n = 6), we measured CBV pulsatility via near-infrared spectroscopy, alongside noninvasive ICP and intraocular pressure (IOP) during 28-h −12° HDT at both nominal (0.04%) and elevated (0.5%) ambient CO2. In our cohort, CBV pulsatility increased significantly over time at cardiac frequencies (0.031 ± 0.009 μM/h increase in total hemoglobin concentration pulsatility amplitude) and Mayer wave frequencies (0.019 ± 0.005 μM/h increase). The HDT-CO2 interaction on pulsatility was not robust but rather driven by one individual. Significant differences between atmospheres were not detected in ICP or IOP. Further work is needed to determine whether individual differences in pulsatility responses to CO2 relate to visual changes in space. NEW & NOTEWORTHY Cerebral blood volume (CBV) pulsatility—as measured by near-infrared spectroscopy—increases over time during −12° head-down tilt at both cardiac and Mayer wave frequencies. CBV pulsatility appeared to increase more under elevated (0.5%) CO2 at Mayer wave frequencies in some individuals. If similar dynamic pulsatility increases occur in astronauts, there is the potential to initiate vascular and possibly other remodeling processes that lead to symptoms associated with sustained increases in intracranial pressure.
Dynamical signatures of isometric force control as a function of age, expertise, and task constraints
Authors: Vieluf Solveig , Sleimen-Malkoun Rita , Voelcker-Rehage Claudia , Jirsa Viktor , Reuter Eva-Maria , Godde Ben , Temprado Jean-Jacques , Huys Raoul 
Published: March 2017

From the conceptual and methodological framework of the dynamical systems approach, force control results from complex interactions of various subsystems yielding observable behavioral fluctuations, which comprise both deterministic (predictable) and stochastic (noise-like) dynamical components. Here, we investigated these components contributing to the observed variability in force control in groups of participants differing in age and expertise level. To this aim, young (18–25 yr) as well as late middle-aged (55−65 yr) novices and experts (precision mechanics) performed a force maintenance and a force modulation task. Results showed that whereas the amplitude of force variability did not differ across groups in the maintenance tasks, in the modulation task it was higher for late middle-aged novices than for experts and higher for both these groups than for young participants. Within both tasks and for all groups, stochastic fluctuations were lowest where the deterministic influence was smallest. However, although all groups showed similar dynamics underlying force control in the maintenance task, a group effect was found for deterministic and stochastic fluctuations in the modulation task. The latter findings imply that both components were involved in the observed group differences in the variability of force fluctuations in the modulation task. These findings suggest that between groups the general characteristics of the dynamics do not differ in either task and that force control is more affected by age than by expertise. However, expertise seems to counteract some of the age effects.NEW & NOTEWORTHY Stochastic and deterministic dynamical components contribute to force production. Dynamical signatures differ between force maintenance and cyclic force modulation tasks but hardly between age and expertise groups. Differences in both stochastic and deterministic components are associated with group differences in behavioral variability, and observed behavioral variability is more strongly task dependent than person dependent.
DNA Damage Induces a Secretory Program in the Quiescent TME that Fosters Adverse Cancer Phenotypes
Authors: Gomez-Sarosi Luis , Sun Yu , Coleman Ilsa , Bianchi-Frias Daniella , Nelson Peter S. 
Published: March 2017

Abstract
Carcinomas develop in complex environments that include a diverse spectrum of cell types that influence tumor cell behavior. These microenvironments represent dynamic systems that contribute to pathologic processes. Damage to DNA is a notable inducer of both transient and permanent alterations in cellular phenotypes. Induction of a DNA damage secretory program is known to promote adverse tumor cell behaviors such as proliferation, invasion, metastasis, and treatment resistance. However, prior studies designed to identify genotoxic stress–induced factors evaluated actively proliferating in vitro cultures of cells such as fibroblasts as experimental models. Conversely, the vast majority of benign cells in a typical tumor microenvironment (TME) are not proliferating but rather exist in quiescent (i.e., G0) or in terminally differentiated states. In this study, the diversity and magnitude of transcriptional responses to genotoxic damage in quiescent prostate fibroblasts were assessed using gene expression profiling. The secretory damage response in quiescent cells was highly concordant with that of actively dividing cells. Quiescent human prostate stroma exposed to genotoxic agents (e.g., mitoxantrone) in vivo resulted in significant upregulation (2.7- to 5.7-fold; P ≤ 0.01) of growth factors and cytokines including IL1β, MMP3, IL6, and IL8. The paracrine effects of damaged quiescent cells consistently increased the proliferation and invasion of prostate cancer cells and promoted cell survival and resistance to apoptosis following exposure to chemotherapy.
Implications: Benign quiescent cells in the TME respond to genotoxic stress by inducing a secretory program capable of promoting therapy resistance. Developing approaches to suppress the secretory program may improve treatment responses. Mol Cancer Res; 15(7); 842–51. ©2017 AACR.