bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammasomes: a novel therapeutic target in pulmonary hypertension?
Authors: Scott Tara Elizabeth , Kemp‐Harper Barbara K , Hobbs Adrian J 
Published: May 2018

AbstractPulmonary hypertension (PH) is a rare, progressive pulmonary vasculopathy characterized by increased mean pulmonary arterial pressure, pulmonary vascular remodelling and right ventricular failure. Current treatments are not curative, and new therapeutic strategies are urgently required. Clinical and preclinical evidence has established that inflammation plays a key role in PH pathogenesis, and recently, inflammasomes have been suggested to be central to this process. Inflammasomes are important regulators of inflammation, releasing the pro‐inflammatory cytokines IL‐1β and IL‐18 in response to exogenous pathogen‐ and endogenous damage‐associated molecular patterns. These cytokines are elevated in PH patients, but whether this is a consequence of inflammasome activation remains to be determined. This review will briefly summarize current PH therapies and their pitfalls, introduce inflammasomes and the mechanisms by which they promote inflammation and, finally, highlight the preclinical and clinical evidence for the potential involvement of inflammasomes in PH pathobiology and how they may be targeted therapeutically.Linked ArticlesThis article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc
The prefrontal cortical endocannabinoid system modulates fear–pain interactions in a subregion‐specific manner
Authors: Rea Kieran , McGowan Fiona , Corcoran Louise , Roche Michelle , Finn David P 
Published: May 2018

Background and PurposeThe emotional processing and coordination of top‐down responses to noxious and conditioned aversive stimuli involves the medial prefrontal cortex (mPFC). Evidence suggests that subregions of the mPFC [infralimbic (IfL), prelimbic (PrL) and anterior cingulate (ACC) cortices] differentially alter the expression of contextually induced fear and nociceptive behaviour. We investigated the role of the endocannabinoid system in the IfL, PrL and ACC in formalin‐evoked nociceptive behaviour, fear‐conditioned analgesia (FCA) and conditioned fear in the presence of nociceptive tone.Experimental ApproachFCA was modelled in male Lister‐hooded rats by assessing formalin‐evoked nociceptive behaviour in an arena previously paired with footshock. The effects of intra‐mPFC administration of AM251 [cannabinoid type 1 (CB1) receptor antagonist/inverse agonist], URB597 [fatty acid amide hydrolase (FAAH) inhibitor] or URB597 + AM251 on FCA and freezing behaviour were assessed.Key ResultsAM251 attenuated FCA when injected into the IfL or PrL and reduced contextually induced freezing behaviour when injected intra‐IfL but not intra‐PrL or intra‐ACC. Intra‐ACC administration of AM251 alone or in combination with URB597 had no effect on FCA or freezing. URB597 attenuated FCA and freezing behaviour when injected intra‐IfL, prolonged the expression of FCA when injected intra‐PrL and had no effect on these behaviours when injected intra‐ACC.Conclusions and ImplicationsThese results suggest important and differing roles for FAAH substrates or CB1 receptors in the PrL, IfL and ACC in the expression of FCA and conditioned fear in the presence of nociceptive tone.Linked ArticlesThis article is part of a themed section on 8th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc
Therapeutic effects of dietary intervention on neuroinflammation and brain metabolism in a rat model of photothrombotic stroke
Authors: Kurtys Ewelina , Casteels Cindy , Real Caroline C. , Eisel Ulrich L. M. , Verkuyl J. Martin , Broersen Laus M. , Klein Hans C. , Dierckx Rudi A. J. O. , Doorduin Janine , de Vries Erik F. J. 
Published: May 2018

SummaryIntroductionA possible target for stroke management is modulation of neuroinflammation. Evidence suggests that food components may exert anti‐inflammatory properties and thus may reduce stroke‐induced brain damage.AimTo investigate the efficacy of a diet, containing anti‐inflammatory ingredients, as treatment for focal ischemic brain damage induced by photothrombotic stroke in the somatosensory cortex of rats.ResultsBrain lesions were surrounded by strong astrogliosis on both day 7 and day 21 after stroke and were accompanied by a trend toward globally decreased glucose metabolism on day 7. The investigational diet applied 2 weeks before the ischemia did not affect astrocyte activation on day 7, but reduced it at day 21. The investigational diet applied immediately after the ischemia, increased astrocyte activation on day 7 and completely reversed this effect on day 21. Moreover, postischemic intervention increased glucose metabolism in somatosensory cortex ipsilateral to the lesion on day 7.ConclusionThis study reveals potentially beneficial effects of a diet containing elevated amounts of anti‐inflammatory nutrients on the recovery from ischemic brain damage. Therefore, dietary intervention can be considered as an adjuvant therapy for recovery from this brain pathology.
Patent foramen ovale closure for patients with cryptogenic stroke: A systematic review and comprehensive meta‐analysis of 5 randomized controlled trials and 14 observational studies
Authors: Chen Xi , Chen Shi‐Dong , Dong Yi , Dong Qiang 
Published: May 2018

SummaryBackgroundPrevious review from randomized controlled trials (RCT) showed that patients with cryptogenic stroke may benefit from patent foramen ovale (PFO) closure. However, the findings from the systematic review were not clear when observational studies were also included.MethodsWe searched MEDLINE, Embase, and Cochrane databases. The primary endpoints were recurrent stroke or transient ischemic attack (TIA). The secondary outcomes were all‐cause death, atrial fibrillation (AF), and hemorrhagic events.ResultsFive randomized trials and fourteen observational studies (6301 participants) were eligible. PFO closure was superior to medical therapy for stroke prevention risk ratios ([RR], 0.38; 95% CI, 0.24‐0.60), but showed increased risk of AF (RR, 4.96; 95% CI, 2.31‐10.7). There was no significant difference in TIA recurrence, death, and hemorrhagic events. Subgroup analyses showed that patients with factors such as substantial residual shunt, the presence of atrial septal aneurysm (ASA), male, and age <45 years had a lower risk of recurrent stroke when PFOs were closed.ConclusionsIn patients with cryptogenic stroke, PFO closure does appeared to be superior to medical therapy in stroke prevention, with an increased incidence of AF. Male, age <45 years, substantial residual shunt, and the history of ASA are the factors that will predict the benefit when PFO is closed.
Retracted:MicroRNA‐219 decreases hippocampal long‐term potentiation inhibition and hippocampal neuronal cell apoptosis in type 2 diabetes mellitus mice by suppressing theNMDARsignaling pathway
Authors: Zhang Ling , Chen Zheng‐Wen , Yang Shu‐Fen , Shaer Muyasi , Wang Ying , Dong Jun‐Jie , Jiapaer Beili 
Published: May 2018

SummaryObjectiveType 2 diabetes mellitus (T2DM) is a complex polygenic disease that causes hyperglycemia and accounts for 90%‐95% of all diabetes mellitus cases. Hence, this study aimed to examine the effects of microRNA‐219 (miR‐219) on inhibition of long‐term potentiation (LTP) and apoptosis of hippocampal neuronal cells in T2DMmice through the N‐methyl‐d‐aspartate receptor (NMDAR) signaling pathway regulation.MethodsThe T2DMmouse models were established, after whichLTPin vivo was recorded by means of electrical biology, and the fasting blood glucose of mice was measured. Next, the density of pyramidal neurons in each group was calculated. Additionally, the expression levels of miR‐219, theNMDARsignaling pathway [NMDAR1 (NR) 1,NR2A, andNR2B), downstream target proteins [calmodulin‐dependent protein kinase‐II(CaMK‐II) andcAMPresponse element binding protein (CREB)], and apoptosis‐related factors [Bcl2‐associated X protein (Bax), c‐caspase‐9 and c‐caspase‐3] in the hippocampal tissues were determined. Finally, immunohistochemistry was applied to detect and measure the positive expression of Bax, caspase‐9, and caspase‐3 proteins.ResultsThe results showed that upregulation of miR‐219 increasesLTPand density of pyramidal neurons in the hippocampal tissues of mice, while it decreases blood glucose of db/db mice. In addition, miR‐219 upregulation also leads to decreasedmRNAlevels ofNR1,NR2A,NR2B, CaMK‐II, andCREBand protein levels ofNR1,NR2A,NR2B, CaMK‐II,CREB, p‐CREB, Bax, c‐caspase‐9, and c‐caspase‐3. Furthermore, upregulation of miR‐219 inhibits positive expression of Bax, caspase‐9, and caspase‐3 proteins, leading to the suppression of hippocampal neuronal cell apoptosis.ConclusionThe findings from this study indicated that the upregulation of miR‐219 decreasesLTPinhibition and hippocampal neuronal cell apoptosis in T2DMmice by downregulating theNMDARsignaling pathway, therefore suggesting that MiR‐219 might be a future therapeutic strategy for T2DM.
Cardiac diseases among liver transplant candidates
Authors: Gitman Marina , Albertz Megan , Nicolau‐Raducu Ramona , Aniskevich Stephen , Pai Sher‐Lu 
Published: May 2018

AbstractImprovements in early survival after liver transplant (LT) have allowed for the selection of LT candidates with multiple comorbidities. Cardiovascular disease is a major contributor to post‐LT complications. We performed a literature search to identify the causes of cardiac disease in the LT population and to describe techniques for diagnosis and perioperative management. As no definite guidelines for preoperative assessment (except for pulmonary heart disease) are currently available, we recommend an algorithm for preoperative cardiac work‐up.
Gender disparities in liver transplant candidates with nonalcoholic steatohepatitis
Authors: Loy Veronica M. , Joyce Cara , Bello Sofia , VonRoenn Natasha , Cotler Scott J. 
Published: May 2018

AbstractBackgroundNonalcoholic steatohepatitis (NASH) is the fastest growing indication for liver transplantation (LT). Data from the UNOS database were used to compare rates of listing and LT between men and women with NASH.MethodsThe study population consisted of 76 149 patients listed for LT between 2005 and 2012, 5 492 (7.2%) of who were listed for NASH. Patient characteristics and outcomes were compared by gender.ResultsNonalcoholic steatohepatitis was a more frequent indication for transplant listing in women than men throughout the study period. Women had lower serum creatinine levels at listing (1.18 ± 0.76 mg/dL vs 1.28 ± 0.79 mg/dL, P < .001) and were less likely to be listed with exception points (17.7% vs 24.9%, P < .001). Transplantation was less common among women than men with NASH (52.4% vs 64.3%), and women were more likely to experience death on the waiting list (17.1% vs 11.4%) In multivariable analysis adjusting for covariates, the rate of LT remained lower for women with NASH (aHR 0.81 95% CI: 0.75‐0.88).ConclusionsWomen with NASH cirrhosis had a higher risk of death on the LT waiting list and were less likely to receive LT compared to men.
Lung transplantation in the Lung Allocation Score era: Medium‐term analysis from a single center
Authors: Iyengar Amit , Kwon Oh Jin , Sanaiha Yas , Eisenring Christian , Biniwale Reshma , Ross David , Ardehali Abbas 
Published: May 2018

AbstractIn 2005, the Lung Allocation Score (LAS) was implemented as the allocation system for lungs in the US. We sought to compare 5‐year lung transplant outcomes before and after the institution of the LAS. Between 2000 and 2011, 501 adult patients were identified, with 132 from January 2000 to April 2005 (Pre‐LAS era) and 369 from May 2005 to December 2011 (Post‐LAS era). Kruskal‐Wallis or chi‐squared test was used to determine significance between groups. Survival was censored at 5 years. Overall, the post‐LAS era was associated with more restrictive lung disease, higher LAS scores, shorter wait‐list times, more preoperative immunosuppression, and more single lung transplantation. In addition, post‐LAS patients had higher O2 requirements with greater preoperative pulmonary impairment. Postoperatively, 30‐day mortality improved in post‐LAS era (1.6% vs 5.3%, P = .048). During the pre‐ and post‐LAS eras, 5‐year survival was 52.3% and 55.3%, respectively (P = .414). The adjusted risk of mortality was not different in the post‐LAS era (P = .139). Freedom from chronic lung allograft dysfunction was significantly higher in the post‐LAS era (P = .002). In this single‐center report, implementation of the LAS score has led to allocation to sicker patients without decrement in short‐ or medium‐term outcomes. Freedom from CLAD at 5 years is improving after LAS implementation.
Motor function daily living skills 5 years after paediatric arterial ischaemic stroke: a prospective longitudinal study
Authors: Cooper Anna N , Anderson Vicki , Greenham Mardee , Hearps Stephen , Hunt Rod W , Mackay Mark T , Ditchfield Michael , Coleman Lee , Monagle Paul , Gordon Anne L 
Published: May 2018

AimTo describe 5‐year motor and functional outcomes after paediatric arterial ischaemic stroke (AIS) and to explore factors associated with poorer long‐term outcome.MethodThirty‐three children (21 males, 12 females) with AIS were recruited to a single‐site, cross‐sectional study, from a previously reported prospective longitudinal stroke outcome study. Children were stratified according to age at diagnosis: neonates (≤30d), preschool (>30d–5y), and school age (≥5y). Motor and functional outcomes were measured at 5 years after stroke. Neurological outcomes were evaluated using the Pediatric Stroke Outcome Measure (PSOM) at 1 month and more than 4 years after stroke.ResultsAt 5 years after stroke, motor function, quality of life, fatigue, adaptive behaviour, activities of daily living, and handwriting speed were significantly poorer than age expectations. The preschool group had the highest percentage of fine and gross motor impairment. Poorer fine motor skills were associated with subcortical‐only lesions and large lesion size. Poorer gross motor outcomes correlated with preschool age, bilateral lesions, and PSOM impairment at 1 month.InterpretationChildren are at elevated risk for motor and functional impairments after AIS, with the preschool age group most vulnerable. Identifying early predictors of poorer outcomes facilitates targeted early intervention and long‐term rehabilitation.What this paper adds

Following paediatric stroke, children are at elevated risk of motor and functional difficulties.

Stroke occurring between 30 days and 5 years of age may result in poorer motor and functional outcomes.
Computerised working memory‐based cognitive remediation therapy does not affect Reading the Mind in The Eyes test performance or neural activity during a Facial Emotion Recognition test in psychosis
Authors: Mothersill David , Dillon Rachael , Hargreaves April , Castorina Marco , Furey Emilia , Fagan Andrew J. , Meaney James F. , Fitzmaurice Brian , Hallahan Brian , McDonald Colm , Wykes Til , Corvin Aiden , Robertson Ian H. , Donohoe Gary 
Published: May 2018

AbstractWorking memory‐based cognitive remediation therapy (CT) for psychosis has recently been associated with broad improvements in performance on untrained tasks measuring working memory, episodic memory and IQ, and changes in associated brain regions. However, it is unclear whether these improvements transfer to the domain of social cognition and neural activity related to performance on social cognitive tasks. We examined performance on the Reading the Mind in the Eyes test (Eyes test) in a large sample of participants with psychosis who underwent working memory‐based CT (N = 43) compared to a control group of participants with psychosis (N = 35). In a subset of this sample, we used functional magnetic resonance imaging (fMRI) to examine changes in neural activity during a facial emotion recognition task in participants who underwent CT (N = 15) compared to a control group (N = 15). No significant effects of CT were observed on Eyes test performance or on neural activity during facial emotion recognition, either at p < 0.05 family‐wise error or at a p < 0.001 uncorrected threshold, within a priori social cognitive regions of interest. This study suggests that working memory‐based CT does not significantly impact an aspect of social cognition which was measured behaviourally and neurally. It provides further evidence that deficits in the ability to decode mental state from facial expressions are dissociable from working memory deficits, and suggests that future CT programmes should target social cognition in addition to working memory for the purposes of further enhancing social function.
Development, organization and plasticity of auditory circuits: Lessons from a cherished colleague
Authors: Lohse Michael , Bajo Victoria M. , King Andrew J. 
Published: May 2018

AbstractRay Guillery was a neuroscientist known primarily for his ground‐breaking studies on the development of the visual pathways and subsequently on the nature of thalamocortical processing loops. The legacy of his work, however, extends well beyond the visual system. Thanks to Ray Guillery's pioneering anatomical studies, the ferret has become a widely used animal model for investigating the development and plasticity of sensory processing. This includes our own work on the auditory system, where experiments in ferrets have revealed the role of sensory experience during development in shaping the neural circuits responsible for sound localization, as well as the capacity of the mature brain to adapt to changes in inputs resulting from hearing loss. Our research has also built on Ray Guillery's ideas about the possible functions of the massive descending projections that link sensory areas of the cerebral cortex to the thalamus and other subcortical targets, by demonstrating a role for corticothalamic feedback in the perception of complex sounds and for corticollicular projection neurons in learning to accommodate altered auditory spatial cues. Finally, his insights into the organization and functions of transthalamic corticocortical connections have inspired a raft of research, including by our own laboratory, which has attempted to identify how information flows through the thalamus.
Structural changes within trophic levels are constrained by within‐family assembly rules at lower trophic levels
Authors: Song Chuliang , Altermatt Florian , Pearse Ian , Saavedra Serguei 
Published: May 2018

AbstractHistorical contingency broadly refers to the proposition that even random historical events can constrain the ecological and evolutionary pathways of organisms and that of entire communities. Focusing on communities, these pathways can be reflected into specific structural changes within and across trophic levels – how species interact with and affect each other – which has important consequences for species coexistence. Using the registry of the last 2000 years of plant introductions and their novel herbivores encountered in Central Europe, we find that the order of arrival of closely related (but not of distantly related) plant species constrained the structural changes within the trophic level formed by herbivore species across the observation period. Because it is difficult for field and lab experiments to be conducted over hundreds of years to record and replay the assembly history of a community, our study provides an alternative to understand how structural changes have occurred across extensive periods of time.
Photosynthetic capacity and leaf nitrogen decline along a controlled climate gradient in provenances of two widely distributed Eucalyptus species
Authors: Crous Kristine Y. , Drake John E. , Aspinwall Michael J. , Sharwood Robert E. , Tjoelker Mark G. , Ghannoum Oula 
Published: May 2018

AbstractClimate is an important factor limiting tree distributions and adaptation to different thermal environments may influence how tree populations respond to climate warming. Given the current rate of warming, it has been hypothesized that tree populations in warmer, more thermally stable climates may have limited capacity to respond physiologically to warming compared to populations from cooler, more seasonal climates. We determined in a controlled environment how several provenances of widely distributed Eucalyptus tereticornis and E. grandis adjusted their photosynthetic capacity to +3.5°C warming along their native distribution range (~16–38°S) and whether climate of seed origin of the provenances influenced their response to different growth temperatures. We also tested how temperature optima (Topt) of photosynthesis and Jmax responded to higher growth temperatures. Our results showed increased photosynthesis rates at a standardized temperature with warming in temperate provenances, while rates in tropical provenances were reduced by about 40% compared to their temperate counterparts. Temperature optima of photosynthesis increased as provenances were exposed to warmer growth temperatures. Both species had ~30% reduced photosynthetic capacity in tropical and subtropical provenances related to reduced leaf nitrogen and leaf Rubisco content compared to temperate provenances. Tropical provenances operated closer to their thermal optimum and came within 3% of the Topt of Jmax during the daily temperature maxima. Hence, further warming may negatively affect C uptake and tree growth in warmer climates, whereas eucalypts in cooler climates may benefit from moderate warming.
Inclusion of alfalfa improves nutritive value and in vitro digestibility of various straw–grass mixed silages in Tibet
Authors: Wang Siran , Li Junfeng , Dong Zhihao , Chen Lei , Shao Tao 
Published: May 2018

AbstractTo enlarge the feed resources and enhance the utilization efficiency of straws as ruminant feed in Tibet, four kinds of local crop straws with tall fescue (Festuca arundinacea Schreb.) based on the ratio of 40/60 (fresh weight) were ensiled with four levels (0, 10%, 20% and 30% of fresh weight) of alfalfa (Medicago sativa L.), respectively. The laboratory silos (1L) were opened after 45 days of ensiling, and the fermentation characteristics, nutritive value and in vitro digestibility of the mixed silages were analysed. The silages including alfalfa had significantly (p < 0.05) or numerically (p > 0.05) higher lactic acid and crude protein contents, lactic acid bacteria counts, in vitro digestibility of dry matter, neutral detergent fibre (NDF) and acid detergent fibre (ADF), and lower NDF and ADF contents than controls. The results suggest that inclusion of alfalfa to mixtures of straws and tall fescue had favourable effects on fermentation quality and obviously improved the nutritive value and in vitro digestibility of mixed silages. This effect was most evident when the inclusion proportion of alfalfa was 30% in oat straw mixed silage.