bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletion of AMPKα1 attenuates the anticontractile effect of perivascular adipose tissue (PVAT) and reduces adiponectin release
Authors: Almabrouk Tarek A M , Ugusman Azizah B , Katwan Omar J , Salt Ian P , Kennedy Simon 
Published: September 2016

Background and PurposePerivascular adipose tissue (PVAT) surrounds most blood vessels and secretes numerous active substances, including adiponectin, which produce a net anticontractile effect in healthy individuals. AMPK is a key mediator of cellular energy balance and may mediate the vascular effects of adiponectin. In this study, we investigated the role of AMPK within PVAT in mediating the anticontractile effect of PVAT.Experimental ApproachEndothelium‐denuded aortic rings from wild‐type (WT; Sv129) and α1AMPK knockout (KO) mice were mounted on a wire myograph. Dose–response curves to the AMPK‐independent vasodilator cromakalim were studied in vessels with and without PVAT, and effect of pre‐incubation with conditioned media and adiponectin on relaxation was also studied. The effect of AMPKα1 KO on the secretory profile of PVAT was assessed by elisa.Key ResultsThoracic aortic PVAT from KO mice was morphologically indistinct from that of WT and primarily composed of brown adipose tissue. PVAT augmented relaxation to cromakalim in WT but not KO aortic rings. Addition of WT PVAT augmented relaxation in KO aortic rings but KO PVAT had no effect in WT rings. PVAT from KO mice secreted significantly less adiponectin and addition of adiponectin to either KO or WT aortic rings without PVAT augmented relaxation to cromakalim. An adiponectin blocking peptide significantly attenuated relaxation in WT rings with PVAT but not in KO rings.Conclusions and ImplicationsAMPKα1 has a critical role in maintaining the anticontractile actions of PVAT; an effect independent of the endothelium but likely mediated through altered adiponectin secretion or sensitivity.Linked ArticlesThis article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue – Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc
Extreme thermal heterogeneity in structurally complex tropical rain forests
Authors: Scheffers Brett R. , Edwards David P. , Macdonald Stewart L. , Senior Rebecca A. , Andriamahohatra Lydou R. , Roslan Nadiah , Rogers Andrew M. , Haugaasen Torbjørn , Wright Patricia , Williams Stephen E. 
Published: September 2016

AbstractMost terrestrial species on Earth are ectothermic and track temperature at small spatial scales, from sun flecks to cool shaded spots. Current assessments of thermal heterogeneity in complex environments are predominately characterized by ambient temperature. This omission of solar radiation may lead to inaccurate conclusions regarding thermoregulation and distribution of species. We use thermal cameras to gather data on temperature heterogeneity in structurally complex rain forest environments. Using thermographic photographs, we capture the multidimensionality of climate created by vegetation by collecting over 76,000 temperature samples within approximately 1 m2 quadrats. The method was tested against three standard methods that record air temperature to determine possible omissions in capturing thermal heterogeneity in four geographic locations—Colombia, Borneo, Madagascar, and Australia. Across all locations, there was greater thermal heterogeneity in surface temperature than captured from ambient temperature technologies. Spatial variability in surface temperature on 1 d was greater than temporal variability of ambient temperature across the entire month, with extreme deviation from ambient temperatures. Importantly, when compared to the lower bounds for optimal performance for five tropical Anolis species, this technology captured thermal regimes that support the thermoregulatory needs of these species, whereas ambient air temperature methods suggested that these species would be in thermal debt. Sampling surface temperature at high resolutions across space in combination with intensive sampling of ambient temperature and informed spatial modeling should improve our understanding of the distribution of ectothermic species living within thermally heterogeneous environments.
Tolerogenic dendritic cells generated with dexamethasone and vitamin D3 regulate rheumatoid arthritis CD4+ T cells partly via transforming growth factor-β1
Authors: Anderson A E , Swan D J , Wong O Y , Buck M , Eltherington O , Harry R A , Patterson A M , Pratt A G , Reynolds G , Doran J-P , Kirby J A , Isaacs J D , Hilkens C M U 
Published: September 2016

SummaryTolerogenic dendritic cells (tolDC) are a new immunotherapeutic tool for the treatment of rheumatoid arthritis (RA) and other autoimmune disorders. We have established a method to generate stable tolDC by pharmacological modulation of human monocyte-derived DC. These tolDC exert potent pro-tolerogenic actions on CD4+ T cells. Lack of interleukin (IL)−12p70 production is a key immunoregulatory attribute of tolDC but does not explain their action fully. Here we show that tolDC express transforming growth factor (TGF)-β1 at both mRNA and protein levels, and that expression of this immunoregulatory cytokine is significantly higher in tolDC than in mature monocyte-derived DC. By inhibiting TGF-β1 signalling we demonstrate that tolDC regulate CD4+ T cell responses in a manner that is at least partly dependent upon this cytokine. Crucially, we also show that while there is no significant difference in expression of TGF-βRII on CD4+ T cells from RA patients and healthy controls, RA patient CD4+ T cells are measurably less responsive to TGF-β1 than healthy control CD4+ T cells [reduced TGF-β-induced mothers against decapentaplegic homologue (Smad)2/3 phosphorylation, forkhead box protein 3 (FoxP3) expression and suppression of (IFN)-γ secretion]. However, CD4+ T cells from RA patients can, nonetheless, be regulated efficiently by tolDC in a TGF-β1-dependent manner. This work is important for the design and development of future studies investigating the potential use of tolDC as a novel immunotherapy for the treatment of RA.
Programmed death-1+ T cells inhibit effector T cells at the pathological site of miliary tuberculosis
Authors: Singh A , Mohan A , Dey A B , Mitra D K 
Published: September 2016

SummaryOptimal T cell activation is vital for the successful resolution of microbial infections. Programmed death-1 (PD-1) is a key immune check-point receptor expressed by activated T cells. Aberrant/excessive inhibition mediated by PD-1 may impair host immunity to Mycobacterium tuberculosis infection, leading to disseminated disease such as miliary tuberculosis (MTB). PD-1 mediated inhibition of T cells in pulmonary tuberculosis and TB pleurisy is reported. However, their role in MTB, particularly at the pathological site, remains to be addressed. The objective of this study was to investigate the role of PD-1–PD-ligand 1 (PD-L1) in T cell responses at the pathological site from patients of TB pleurisy and MTB as clinical models of contained and disseminated forms of tuberculosis, respectively. We examined the expression and function of PD-1 and its ligands (PD-L1–PD-L2) on host immune cells among tuberculosis patients. Bronchoalveolar lavage-derived CD3 T cells in MTB expressed PD-1 (54·2 ± 27·4%, P ≥ 0·0009) with significantly higher PD-1 ligand-positive T cells (PD-L1: 19·8 ± 11·8%; P ≥ 0·019, PD-L2: 12·6 ± 6·2%; P ≥ 0·023), CD19+ B cells (PD-L1: 14·4 ± 10·4%; P ≥ 0·042, PD-L2: 2·6 ± 1·43%; not significant) and CD14+ monocytes (PD-L1: 40·2 ± 20·1%; P ≥ 0·047, PD-L2: 22·4 ± 15·6%; P ≥ 0·032) compared with peripheral blood (PB) of MTB and healthy controls. The expression of PD-1 was associated with a diminished number of cells producing effector cytokines interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)−2 and elevated apoptosis. Locally accumulated T cells were predominantly PD-1+–PD-L1+, and blocking this pathway restores the protective T cell response. We conclude that M. tuberculosis exploits the PD-1 pathway to evade the host immune response by altering the T helper type 1 (Th1) and Th2 balance at the pathological site of MTB, thereby favouring disease dissemination.
Anti-inflammatory effects of infliximab in mice are independent of tumour necrosis factor α neutralization
Authors: Assas B M , Levison S E , Little M , England H , Battrick L , Bagnall J , McLaughlin J T , Paszek P , Else K J , Pennock J L 
Published: September 2016

Summary
Infliximab (IFX) has been used repeatedly in mouse preclinical models with associated claims that anti-inflammatory effects are due to inhibition of mouse tumour necrosis factor (TNF)-α. However, the mechanism of action in mice remains unclear. In this study, the binding specificity of IFX for mouse TNF-α was investigated ex vivo using enzyme-linked immunosorbent assay (ELISA), flow cytometry and Western blot. Infliximab (IFX) did not bind directly to soluble or membrane-bound mouse TNF-α nor did it have any effect on TNF-α-induced nuclear factor kappa B (NF-κB) stimulation in mouse fibroblasts. The efficacy of IFX treatment was then investigated in vivo using a TNF-α-independent Trichuris muris-induced infection model of chronic colitis. Infection provoked severe transmural colonic inflammation by day 35 post-infection. Colonic pathology, macrophage phenotype and cell death were determined. As predicted from the in-vitro data, in-vivo treatment of T. muris-infected mice with IFX had no effect on clinical outcome, nor did it affect macrophage cell phenotype or number. IFX enhanced apoptosis of colonic immune cells significantly, likely to be driven by a direct effect of the humanized antibody itself. We have demonstrated that although IFX does not bind directly to TNF-α, observed anti-inflammatory effects in other mouse models may be through host cell apoptosis. We suggest that more careful consideration of xenogeneic responses should be made when utilizing IFX in preclinical models.
Atmospheric temperature and pressure influence the onset of spontaneous pneumothorax
Authors: Motono Nozomu , Maeda Sumiko , Honda Ryumon , Tanaka Makoto , Machida Yuichiro , Usuda Katsuo , Sagawa Motoyasu , Uramoto Hidetaka 
Published: September 2016

AbstractBackgroundThe aim of the study was to examine the influence of the changes in the atmospheric temperature (ATemp) and the atmospheric pressure (APres) on the occurrence of a spontaneous pneumothorax (SP).Patients and methodsFrom January 2000 to March 2014, 192 consecutive SP events were examined. The ATemp and APres data at the onset of SP, as well as those data at 12, 24, 36, 48, 60, and 72 h prior to the onset time, were analyzed.ResultsThe frequencies of SP occurrence were not statistically different according to the months or seasons, but were statistically different according to the time period (P < .01) and SP events occurred most frequently from 12:00 to 18:00. SP events frequently occurred at an ATemp of 25 degrees Celsius or higher. There was a significantly negative correlation between the APres and the ATemp at the SP onset time. The values of change in the APres from 36 to 24 h prior to SP onset were significantly lower than the preceding values.ConclusionsIn this study, we observed that a SP event was likely to occur in the time period from 12:00 to 18:00, at an ATemp of 25 degrees Celsius or higher, and at 24–36 h after a drop of APres.
Using gamification to develop academic writing skills in dental undergraduate students
Authors: El Tantawi Maha , Sadaf Shazia , AlHumaid Jehan 
Published: September 2016

AbstractObjectivesTo assess the satisfaction of first‐year dental students with gamification and its effect on perceived and actual improvement of academic writing.MethodsTwo first‐year classes of dental undergraduate students were recruited for the study which extended over 4 months and ended in January 2015. A pre‐intervention assessment of students’ academic writing skills was performed using criteria to evaluate writing. The same criteria were used to evaluate the final writing assignment after the intervention. Students’ satisfaction with game aspects was assessed. The per cent change in writing score was regressed on scores of satisfaction with game aspects controlling for gender. Perceived improvement in writing was also assessed.ResultsData from 87 (94.6%) students were available for analysis. Students’ overall satisfaction with the gamified experience was modest [mean (SD) = 5.9 (2.1)] and so was their overall perception of improvement in writing [mean (SD) = 6.0 (2.2)]. The per cent score of the first assignment was 35.6 which improved to 80 in the last assignment. Satisfaction with playing the game was significantly associated with higher percentage of improvement in actual writing skills [regression coefficient (95% confidence interval) = 21.1 (1.9, 40.2)].ConclusionUsing gamification in an obligatory course for first‐year dental students was associated with an improvement in academic writing skills although students’ satisfaction with game aspects was modest and their willingness to use gamification in future courses was minimal.
Hyperdiploidy as a rare event that accompanies poor prognosis markers in CLL
Authors: González‐Gascón y Marín Isabel , Martín Ana África , Hernández‐Sanchez María , Robledo Cristina , Hermosín María Lourdes , de las Heras Natalia , Lacalle Laura , Galende Josefina , de Arriba Felipe , Rodríguez‐Vicente Ana Eugenia , Hernández José‐Ángel , Hernández‐Rivas Jesús María 
Published: September 2016

AbstractThe presence of chromosomal gains other than trisomy 12 in chronic lymphocytic leukaemia (CLL) is unusual. However, some patients may show gains on several chromosomes simultaneously suggesting a hyperdiploid karyotype.ObjectiveThe objective of this study was to analyse by FISH the frequency and prognostic impact of hyperdiploidy in CLL.MethodA review of 1359 consecutive cases diagnosed with CLL referred for FISH analysis to a unique institution was carried out. Hyperdiploidy was considered when a gain of at least three of the five FISH probes used was observed.ResultsSeven cases (0.51%) with hyperdiploidy were found, confirming that it is a rare event in this disease. Although most patients presented with early Binet stages at diagnosis, six of seven (86%) shortly progressed. The median of time to the first therapy (TTFT) and overall survival (OS) for the patients with hyperdiploidy were short (1.4 months and 20 months, respectively). Moreover, comparing them with a control group of patients (non‐hyperdiploid) with completed follow‐up data, TTFT and OS of the patients with hyperdiploidy were significantly shorter than the control group.ConclusionThe presence of hyperdiploidy is uncommon and probably associated with poor prognostic markers in CLL.
Transient and persistent behavioral and molecular changes in primiparous female Wistar rats
Authors: Naik Roshan R. , de Jong Trynke R. 
Published: September 2016

AbstractMotherhood brings about a multitude of behavioral and physiological changes in dams and some of these persist until after weaning. We studied behavioral changes associated with reproductive experience at lactating day (LD)8, at weaning (LD21), and 28 days post‐weaning (PW28) compared to nulliparous (NP) females. Furthermore, in another cohort of animals, we quantified mRNA expression of five target genes known to be associated with maternal experience: arginin‐vasopressin(Avp) and its 1A receptor(Avpr1a), oxytocin(Oxt) and its receptor(Oxtr), and corticotropin‐releasing hormone(Crh) in three key maternal region: the medial preoptic area (MPOA), bed nucleus of the stria terminalis (BNST) and paraventricular hypothalamic nucleus(PVN). Although dams were slightly less anxious than NP at LD8, this effect did not persist at LD21 and PW28. No differences in social preference were found between the four groups. In the maternal responsiveness test (MRT), LD8 and LD21 dams were immediately responsive to pups whereas NP largely avoided the pups throughout 12‐day period. PW28 females were significantly more responsive to pups than NP females, but less than LD8 and LD21 females. The mRNA expression of Avp in the PVN, Avpr1a in the BNST and Oxtr in the MPOA and BNST was increased, whereas mRNA expression of Avpr1a was reduced in the PVN, at LD8 compared to NP. Although Oxtr in the BNST and Avp in the PVN were still somewhat (non‐significantly) increased at LD21, all levels of gene expression had normalized at PW28. Our results emphasize the transient nature of these behavioral and molecular adaptations, except for a persistent up‐regulation of maternal responsiveness.
Intralaminar and tectal projections to the subthalamus in the rat
Authors: Kita Takako , Shigematsu Naoki , Kita Hitoshi 
Published: September 2016

AbstractProjections from the posterior intralaminar thalamic nuclei and the superior colliculus (SC) to the subthalamic nucleus (STN) and the zona incerta (ZI) have been described in the primate and rodent. The aims of this study was to investigate several questions on these projections, using modern neurotracing techniques in rats, to advance our understanding of the role of STN and ZI. We examined whether projection patterns to the subthlamus can be used to identify homologues of the primate centromedian (CM) and the parafascicular nucleus (Pf) in the rodent, the topography of the projection including what percent of intralaminar neurons participate in the projections, and electron microscopic examination of intralaminar synaptic boutons in STN. The aim on the SC‐subthalamic projection was to examine whether STN is the main target of the projection. This study revealed: (i) the areas similar to primate CM and Pf could be recognized in the rat; (ii) the Pf‐like area sends a very heavy topographically organized projection to STN but very sparse projection to ZI, which suggested that Pf might control basal ganglia function through STN; (iii) the projection from the CM‐like area to the subthalamus was very sparse; (iv) Pf boutons and randomly sampled asymmetrical synapses had similar distributions on the dendrites of STN neurons; and (v) the lateral part of the deep layers of SC sends a very heavy projection to ZI and moderate to sparse projection to limited parts of STN, suggesting that SC is involved in a limited control of basal ganglia function.
Fixed 50:50 mixture of nitrous oxide and oxygen to reduce lumbar‐puncture‐induced pain: a randomized controlled trial
Authors: Moisset X. , Sia M. A. , Pereira B. , Taithe F. , Dumont E. , Bernard L. , Clavelou P. 
Published: September 2016

Background and purposeLumbar puncture (LP) has been frequently performed for more than a century. This procedure is still stressful and often painful. The aim of the study was to evaluate the efficacy of a fixed 50% nitrous oxide−oxygen mixture compared to placebo to reduce immediate procedural pain and anxiety during LP.MethodsA randomized controlled trial was conducted involving adults who needed a cerebrospinal fluid analysis. Patients were randomly assigned to inhale either a fixed 50% nitrous oxide−oxygen mixture (50% N2O−O2) or medical air (22% O2−78% N2). Cutaneous application of a eutectic mixture of local anaesthetics was systematically done and all LPs were performed with pencil point 25G needles (20G introducer needle). The primary end‐point was the maximal pain level felt by the patient during the procedure, the maximal anxiety level being a secondary outcome, both measured using a numerical rating scale (0–10).ResultsA total of 66 consecutive patients were randomized. The analysis was intention to treat. The maximal pain was 4.9 ± 2.7 for the 33 patients receiving air and 2.7 ± 2.7 for the 33 receiving 50% N2O−O2 (P = 0.002). Similarly, the maximal LP‐induced anxiety was 4.5 ± 3.1 vs. 2.6 ± 2.6 (P = 0.009), respectively. The number needed to treat to avoid one patient undergoing significant pain (pain score ≥ 4/10) was 2.75. Body mass index >25 kg/m2 was significantly associated with higher pain intensity (P = 0.03). No serious adverse events were attributable to 50% N2O−O2 inhalation.ConclusionsInhalation of a fixed 50% N2O−O2 mixture is efficient to reduce LP‐induced pain and anxiety.
HLA‐B*40:02 and DRB1*04:03 are risk factors for oxcarbazepine‐induced maculopapular eruption
Authors: Moon Jangsup , Kim Tae‐Joon , Lim Jung‐Ah , Sunwoo Jun‐Sang , Byun Jung‐Ick , Lee Soon‐Tae , Jung Keun‐Hwa , Park Kyung‐Il , Jung Ki‐Young , Jeon Daejong , Yu Kyung‐Sang , Jang In‐Jin , Chu Kon , Lee Sang Kun 
Published: September 2016

SummaryObjectiveOxcarbazepine (OXC) is a widely used antiepileptic drug for the treatment of partial seizures that was developed through structural variation of carbamazepine. Although OXC has a lower risk of cutaneous adverse drug reactions (cADRs) than carbamazepine, cADRs ranging from maculopapular eruption (MPE) to the more severe Stevens‐Johnson syndrome and toxic epidermal necrolysis still limit the use of OXC in some patients. A few human leukocyte antigen (HLA)–related genetic risk factors for carbamazepine‐induced cADRs have been identified. However, the HLA‐related genetic risk factors associated with OXC‐induced cADRs are unknown.MethodsA total of 40 patients who experienced OXC‐induced MPE and 70 patients who were tolerant to OXC treatment were included in the study. Genomic DNA was extracted from the peripheral blood of these patients, and high‐resolution HLA genotyping was performed.ResultsThe HLA‐B*40:02 and HLA‐DRB1*04:03 alleles were significantly associated with OXC‐induced MPE compared with the OXC‐tolerant group (odds ratio [OR] 4.33, p = 0.018 and OR 14.64, p = 0.003, respectively) and the general Korean population (OR 4.04, p = 0.001 and OR 3.11, p = 0.019, respectively). The HLA‐B*15:01 genetic frequency was significantly lower in the OXC‐MPE group compared to the OXC‐tolerant group (OR 0.18, p = 0.016) and the Korean population (OR 0.22, p = 0.030). The allele frequencies of well‐known HLA‐related risk factors for carbamazepine‐induced cADRs (HLA‐B*15:02, A*31:01 and B*15:11) were not different among the three groups.SignificanceThis study is the first to demonstrate an association of HLA‐B*40:02 and HLA‐DRB1*04:03 with OXC hypersensitivity using a large cohort of patients with OXC‐induced MPE. These findings should be confirmed in future studies in different ethnic groups.
Angler apps as a source of recreational fisheries data: opportunities, challenges and proposed standards
Authors: Venturelli Paul A , Hyder Kieran , Skov Christian 
Published: September 2016

AbstractRecreational fisheries surveys are limited in time and place in many countries. This lack of data limits scientific understanding and sustainable management. Smartphone applications (apps) allow anglers to record the details of their fishing trips and catches. In this study, we describe the opportunities and challenges associated with angler apps as a source of recreational fisheries data, and propose minimum standards for data collection via angler apps. Angler apps are a potentially valuable source of conventional and novel data that are both frequent and extensive, and an opportunity to engage anglers through data sharing and citizen science. Realizing this potential requires that we address significant challenges related to angler recruitment and retention, data quality and bias, and integration with existing fisheries programmes. We propose solutions to each of these challenges. Given that the angler app market is diverse, competitive and unpredictable, we emphasize minimum standards for data collection as a way to ensure large and reliable data sets that can be compared and integrated across apps. These standards relate to trips and catches, and angler demographics and behaviour, and should be supported through consultation and research. Angler apps have the potential to fundamentally change how anglers interact with the resource and with management.