bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral vasoconstriction induced by β‐adrenoceptor blockers: a systematic review and a network meta‐analysis
Authors: Khouri Charles , Jouve Thomas , Blaise Sophie , Carpentier Patrick , Cracowski Jean‐Luc , Roustit Matthieu 
Published: April 2016

AimPeripheral vasoconstriction has long been described as a vascular adverse effect of β‐adrenoceptor blockers. Whether β‐adrenoceptor blockers should be avoided in patients with peripheral vascular disease depends on pharmacological properties (e.g. preferential binding to β1‐adrenoreceptors or intrinsic sympathomimetic activity). However, this has not been confirmed in experimental studies. We performed a network meta‐analysis in order to assess the comparative risk of peripheral vasoconstriction of different β‐adrenoceptor blockers.MethodWe searched for randomized controlled trials (RCTs) including β‐adrenoceptor blockers that were published in core clinical journals in the Pubmed database. All RCTs reporting peripheral vasoconstriction as an adverse effect of β‐adrenoceptor blockers and controls were included. Sensitivity analyses were conducted including possibly confounding covariates (latitude, properties of the β‐adrenoceptor blockers, e.g. intrinsic sympathomimetic activity, vasodilation, drug indication, drug doses). The protocol and the detailed search strategy are available online (PROSPERO registry CRD42014014374).ResultsAmong 2238 records screened, 38 studies including 57 026 patients were selected. Overall, peripheral vasoconstriction was reported in 7% of patients with β‐adrenoceptor blockers and 4.6% in the control groups (P < 0.001), with heterogeneity among drugs. Atenolol and propranolol had a significantly higher risk than placebo, whereas pindolol, acebutolol and oxprenolol had not.ConclusionOur results suggest that β‐adrenoceptor blockers have variable propensity to enhance peripheral vasoconstriction and that it is not related to preferential binding to β1‐adrenoceptors. These findings challenge FDA and European recommendations regarding precautions and contra‐indications of use of β‐adrenoceptor blockers and suggest that β‐adrenoceptor blockers with intrinsic sympathomimetic activity could be safely used in patients with peripheral vascular disease.
Free and complexed-secretory immunoglobulin A triggers distinct intestinal epithelial cell responses
Authors: Salerno-Goncalves R , Safavie F , Fasano A , Sztein M B 
Published: April 2016

Summary
Secretory immunoglobulin A (SIgA) antibodies play an important role in protecting the mucosal surfaces against pathogens and maintaining homeostasis with the commensal microbiota. Because a substantial portion of the gut microbiota is coated with SIgA, we hypothesized that microbiota–SIgA complexes are important for the maintenance of gut homeostasis. Here we investigated the relationship between microbiota–SIgA complexes and inflammatory epithelial cell responses. We used a multi-cellular three-dimensional (3D) organotypical model of the human intestinal mucosa composed of an intestinal epithelial cell line and primary human lymphocytes/monocytes, endothelial cells and fibroblasts. We also used human SIgA from human colostrum, and a prominent bacterial member of the first colonizers, Escherichia coli, as a surrogate commensal. We found that free and microbiota-complexed SIgA triggered different epithelial responses. While free SIgA up-regulated mucus production, expression of polymeric immunoglobulin receptor (pIgR) and secretion of interleukin-8 and tumoir necrosis factor-α, microbiota-complexed SIgA mitigated these responses. These results suggest that free and complexed SIgA have different functions as immunoregulatory agents in the gut and that an imbalance between the two may affect gut homeostasis.
The regulatory role of interferon-γ producing gamma delta T cells via the suppression of T helper 17 cell activity in bleomycin-induced pulmonary fibrosis
Authors: Segawa S , Goto D , Iizuka A , Kaneko S , Yokosawa M , Kondo Y , Matsumoto I , Sumida T 
Published: April 2016

Summary
Interstitial pneumonia (IP) is a chronic progressive interstitial lung disease associated with poor prognosis and high mortality. However, the pathogenesis of IP remains to be elucidated. The aim of this study was to clarify the role of pulmonary γδT cells in IP. In wild-type (WT) mice exposed to bleomycin, pulmonary γδT cells were expanded and produced large amounts of interferon (IFN)-γ and interleukin (IL)-17A. Histological and biochemical analyses showed that bleomycin-induced IP was more severe in T cell receptor (TCR-δ-deficient (TCRδ–/–) mice than WT mice. In TCRδ–/– mice, pulmonary IL-17A+CD4+ Τ cells expanded at days 7 and 14 after bleomycin exposure. In TCRδ–/– mice infused with γδT cells from WT mice, the number of pulmonary IL-17A+ CD4+ T cells was lower than in TCRδ–/– mice. The examination of IL-17A–/– TCRδ–/– mice indicated that γδT cells suppressed pulmonary fibrosis through the suppression of IL-17A+CD4+ T cells. The differentiation of T helper (Th)17 cells was determined in vitro, and CD4+ cells isolated from TCRδ–/– mice showed normal differentiation of Th17 cells compared with WT mice. Th17 cell differentiation was suppressed in the presence of IFN-γ producing γδT cells in vitro. Pulmonary fibrosis was attenuated by IFN-γ-producing γδT cells through the suppression of pulmonary IL-17A+CD4+ T cells. These results suggested that pulmonary γδT cells seem to play a regulatory role in the development of bleomycin-induced IP mouse model via the suppression of IL-17A production.
Stress intensity factors for surface cracks in single‐edge notch bend specimen by a three‐dimensional weight function method
Authors: Zhao X C , Wu X R , Newman J C , Tong D H 
Published: April 2016

AbstractStress intensity factors for half‐elliptical surface cracks at a semi‐circular notch in a recently developed single‐edge notch bend specimen are determined for a wide range of geometrical parameters using a three‐dimensional weight function method. Two load cases of pin loading and uniform remote tension are considered. The results are in good agreement with abaqus/franc3d finite element analysis. It is found that the Ziegler–Newman engineering similitude approach (programmed into the Fatigue Crack Growth Structural Analysis life‐prediction code) produces good results for a wide range in a/c ratios. Expressions by multi‐variable curve fitting to the weight function results are presented for easy engineering applications.
Aldo‐keto reductase family 1 member B10 is associated with hepatitis B virus‐related hepatocellular carcinoma risk
Authors: Mori Masashi , Genda Takuya , Ichida Takafumi , Murata Ayato , Kamei Masato , Tsuzura Hironori , Sato Shunsuke , Narita Yutaka , Kanemitsu Yoshio , Ishikawa Sachiko , Kikuchi Tetsu , Shimada Yuji , Hirano Katsuharu , Iijima Katsuyori , Sugimoto Ken , Wada Ryo , Nagahara Akihito , Watanabe Sumio 
Published: April 2016

AimRecent reports have indicated that aldo‐keto reductase family 1 member B10 (AKR1B10), a cancer‐related oxidoreductase, was upregulated in some chronic liver diseases. However, few studies have reported AKR1B10 expression in chronic hepatitis B virus (HBV)‐infected patients. The aim of the present study was to analyze AKR1B10 expression and its relevance on hepatocellular carcinoma (HCC) development in patients with chronic HBV infection.MethodsExpression of AKR1B10 in the liver of 119 chronic HBV‐infected patients was assessed and quantified immunohistochemically. A multivariate Cox model was used to estimate the hazard ratios of AKR1B10 expression for HCC development. The cumulative incidences of HCC were evaluated using Kaplan–Meier analysis.ResultsExpression of AKR1B10 in the study cohort ranged from 0% to 84%. During the median follow‐up time (6.2 years), 13 patients developed HCC. Multivariate analysis revealed that high AKR1B10 expression (≥15%) was an independent risk factor for HCC (hazard ratio, 10.8; 95% confidence interval, 3.0–38.6; P < 0.001). The 5‐year cumulative incidences of HCC were 20.6% and 2.6% in patients with high and low AKR1B10 expression, respectively (P < 0.001). Patients with high AKR1B10 expression had significantly higher alanine aminotransferase levels during follow‐up than those with low expression, even though antiviral treatment decreased HBV‐DNA levels in both groups.ConclusionChronic HBV‐infected patients with high hepatic AKR1B10 expression had an increased risk of HCC development. This suggests that AKR1B10 upregulation might play a role in the early stages of HBV‐related hepatocarcinogenesis.
A portal pressure cut‐off of 15 versus a cut‐off of 20 for prevention of small‐for‐size syndrome in liver transplantation: A comparative study
Authors: Osman Ayman M.A. , Hosny Adel A. , El‐Shazli Mostafa A. , Uemoto Shinji , Abdelaziz Omar , Helmy Ayman S. 
Published: April 2016

AimPortal hypertension has recently been implicated in the pathogenesis of small‐for‐size syndrome (SFSS) in adult‐to‐adult living‐donor liver transplantation (A‐LDLT). The aim of our study is to compare the portal venous pressure (PVP) cut‐off values of 15 mmHg and 20 mmHg in terms of prevention of SFSS in A‐LDLT.MethodsSeventy‐six patients underwent A‐LDLT. A PVP <20 mmHg at the end of the operation was targeted using graft inflow modulation. Patients were divided into two groups: group A, final PVP <15 mmHg; and group B, final PVP 15–19 mmHg. Peak serum bilirubin and peak international normalized ratio in the first month after A‐LDLT, as well as hepatic encephalopathy, SFSS, 90‐day morbidity, and mortality were observed in both groups.ResultsFinal PVP was well controlled below 20 mmHg in all patients (group A, n = 39; group B, n = 37). Six patients suffered SFSS in group B (16.2%) compared to one patient (2.6%) in group A (P = 0.04). Nine patients died in group B (24.3%), four of whom died of SFSS, compared to three patients in group A (7.7%) (P = 0.047).ConclusionA PVP cut‐off of 15 mmHg seems to be a more appropriate target level than a cut‐off of 20 mmHg for prevention of postoperative SFSS in A‐LDLT.
MicroRNA223 promotes pathogenic T‐cell development and autoimmune inflammation in central nervous system in mice
Authors: Satoorian Tiffany , Li Bo , Tang Xiaolei , Xiao Jidong , Xing Weirong , Shi Weixing , Lau Kin‐Hing William , Baylink David J. , Qin Xuezhong 
Published: April 2016

SummaryMultiple sclerosis (MS) is an incurable central nervous system autoimmune disease. Understanding MS pathogenesis is essential for the development of new MS therapies. In the present study, we identified a novel microRNA (miR) that regulates experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Expression of miR223 was up‐regulated specifically in spinal cords and lymphoid organs but not in other examined tissues. A global miR223 knockout (miR223−/−) in mice led to a significant delay in EAE onset, reduction in spinal cord lesion, and lessening of neurological symptoms. These protective effects could be reproduced in bone marrow chimeras reconstituted with miR223−/− haematopoietic stem cells. We also found that miR223 deficiency reduced T helper type 1 (Th1) and Th17 infiltration into spinal cords. To address underlying mechanisms, we investigated the role of miR223 in regulating the function, development and interaction of the major immune cells. Expression of the genes associated with dendritic cell (DC) activation (CD86 and MHC II) and Th1 and Th17 differentiation [interleukin‐12 (IL‐12) and IL‐23, respectively] was significantly decreased in the spleens of miR223−/− mice bearing EAE. The miR223−/− DCs expressed significantly lower levels of basal and lipopolysaccharide‐induced IL‐12 and IL‐23 compared with the wild‐type DCs. These data are consistent with the observed lower efficiency of miR223−/− DCs to support Th1 and Th17 differentiation from naive T cells over‐expressing an EAE antigen‐specific T‐cell receptor. Our data suggest that miR223 promotes EAE, probably through enhancing DC activation and subsequently the differentiation of naive T cells toward Th1 and Th17 effector cells.
Is suicide assessment harmful to participants? Findings from a randomized controlled trial
Authors: Harris Keith M. , Goh Melissa Ting‐Ting 
Published: April 2016

AbstractThere is considerable debate on whether suicide assessment carries an iatrogenic risk for participants/patients. A double‐blind randomized controlled trial (registration: R000022314) tested the emotional impact of suicide assessment on participants (n = 259) randomly assigned to experimental (n = 122) or control conditions (n = 137). The experimental condition included the Suicidal Affect‐Behavior‐Cognition Scale and intensive death‐related questions, the control condition a quality of life scale. Both included measures of depression, social support and loneliness. Affective states were assessed immediately before and after testing, and research biases minimized. Post‐test debriefing interviews collected qualitative reactions. Experimental participants ranged from nonsuicidal to highly suicidal. Between‐groups ANCOVAs and repeated measures ANOVAs showed no differences by study condition, and no pre‐post‐test affect changes for either condition or suicidal participants (P > 0.10), supporting the null hypothesis of no iatrogenic effects. However, depressive participants in both conditions showed significant decreases in positive affect (P < 0.05). Smallest real difference (SRD) scores approximated clinically meaningful differences and showed 20% of participants had a significant positive survey reaction, 24% a negative reaction, with the rest neutral. Linear regressions revealed depressive symptoms and perceived family support, but not suicidality or other factors, predicted negative affect changes, which was supported by qualitative findings. Social desirability bias was also found in qualitative survey responses. No evidence of iatrogenic effects of suicide assessment were found. Recommendations are made to counter possible negative assessment effects on depressive participants/patients, and nurses and other caregivers are encouraged to talk to patients about suicidal symptoms.
Mental health nurses’ contributions to community mental health care: An Australian study
Authors: Heslop Brett , Wynaden Dianne , Tohotoa Jenny , Heslop Karen 
Published: April 2016

AbstractAustralian mental health policy is focused on providing mental health care in the community setting and community mental health teams provide services to clients in a shared model with primary care. The historical literature reports that community mental health nurses’ experience high levels of stress and are often allocated the most complex and challenging clients managed by the team. Yet information on their specific roles remains limited. This paper reports on research conducted at one Australian public mental health service to identify the components of the community mental health nursing role and to quantify the time nurses spent in each component during the study period. Six focus groups were conducted with community mental health nurses to identify their perceived role within the team. Data analysis identified 18 components of which 10 were related to direct clinical contact with clients and eight covered administrative and care coordination activities. A data collection tool based on the findings of the focus groups was designed and nurses recorded workload data on the tool in 15‐min intervals over a 4‐week period. Seventeen nurses collected 1528 hours of data. Internal coordination of care was identified as the top workload item followed by clinical documentation and national data collection responsibilities supporting the complexity of the community mental health nursing role. The high rating attached to the internal coordination of care role demonstrates an important contribution that community mental health nurses make to the functioning of the team and the delivery of quality mental health care.
Effects of anti‐human T lymphocyte immune globulins in patients: new or old
Authors: Wang Diane C. , Wang Xiangdong , Chen Chengshui 
Published: April 2016

AbstractMultiple studies demonstrated that anti‐human T lymphocyte immune globulins (ATG) can decrease the incidence of acute and chronic graft rejection in cell or organ transplants. However, further in‐depth study indicates that different subgroups may benefit from either different regimes or alteration of them. Studies among renal transplant patients indicate that low immunological risk patients may not gain the same amount of benefit and thus tilt the risk versus benefit consideration. This may hold true for low immunological risk patients receiving other organ transplants and would be worth further investigation. The recovery time of T cells and natural killer (NK) cells also bears consideration and the impact that it has on the severity and incidence of opportunistic infections closely correlated with the dosage of ATG. The use of lower doses of ATG in combination with other induction medications may offer a solution. The finding that ATG may lose efficacy in cases of multiple transplants or re‐transplants in the case of heart transplants may hold true for other transplantations. This may lead to reconsideration of which induction therapies would be most beneficial in the clinical setting. These studies on ATG done on different patient groups will naturally not be applicable to all, but the evidence accrued from them as a whole may offer us new and different perspectives on how to approach and potentially solve the clinical question of how to best reduce the mortality associated with chronic host‐versus‐graft disease.
Evaluating diagnostic tests
Authors: Kennedy Ashley Graham 
Published: April 2016

AbstractAlthough much has been written on the role of randomized controlled trials and mechanistic reasoning in the evaluation of therapeutic treatments, philosophers of medicine have not yet turned their attention to the question of how diagnostic tests and procedures should be evaluated. I aim to begin to fill this gap by examining each of the following questions:

What is the best way to determine the accuracy of a diagnostic test?
What is the best way to determine the clinical effectiveness of a diagnostic test?
Can an accurate diagnostic test be considered medically valuable even if it is not clinically effective?
I argue that while diagnostic accuracy is a minimum requirement for both clinical effectiveness and medical value, accuracy and effectiveness are not sufficient for determining the value of a diagnostic test, because diagnostic value extends beyond patient outcomes.
Effect of Selected Physico‐Chemical Factors on Bacterial Β‐Cryptoxanthin Degradation: Stability and Kinetic Study
Authors: Mitra Ruchira , Samanta Amit Kumar , Chaudhuri Surabhi , Dutta Debjani 
Published: April 2016

AbstractCarotenoids are promising dietary supplements to human population due to its potential nutraceutical benefits. Their stability in food system is a big concern for food industry. In this study, stability of β‐cryptoxanthin (β‐CRX), a yellow colored pro‐vitamin A xanthophyll, extracted from a previously isolated bacterium Kocuria marina DAGII, was studied under different processing conditions by first‐order linear regression analysis and two‐way ANOVA. The results indicated that the β‐CRX resisted thermal treatments up to 50°C with degradation rate constants (k) of 0.3731–0.8661 h−1, thermal death times (D values) of 6.1715–2.6586 h, a z value of 169.5°C, an activation energy (
) of

, enthalpy
and entropy of activation (ΔS) of
and
, respectively, over the temperature range of
–
. The resulting positive Gibbs free energy change (
) indicated the non‐spontaneous nature of the degradation reaction. Neutral to basic pH was favorable for the β‐CRX processing. Light induced degradation was high
resulting into complete degradation of the β‐CRX. Furthermore, addition of metallic ions significantly affected the β‐CRX stability, however, it was stable in presence of
,
, oxidant
and reductant
. Till date there has been no detailed report on the degradation kinetics of β‐CRX, obtained from microbial source. Hence considering all the tested parameters, this study is significant for using the extracted bacterial β‐CRX as a dietary supplement.Practical Applicationsβ‐CRX is a bioactive compound having great potential as a dietary supplement because of its therapeutic and immune‐enhancing properties, especially the pro‐vitamin A activity, anti‐oxidant and anti‐cancer properties. But, the stability of β‐CRX during food processing is a big concern due to the presence of polyunsaturated chains of conjugated double bonds. Thus, the present research work explores the stability of β‐CRX, extracted from Kocuria marina DAGII, under different selected parameters that are important for processing of food. This study gives an idea about the effective β‐CRX remaining after it is being exposed to high temperature, acidic pH, light and oxidizing environment. Results indicate the favorable conditions that should be maintained during the β‐CRX processing for industrial application. Assessment of the chemical kinetics and application of the mathematical model will also provide information for designing an optimum process so that minimum degradation of β‐CRX takes place.
Adiponectin regulates aquaglyceroporin expression in hepatic stellate cells altering their functional state
Authors: Tardelli Matteo , Moreno‐Viedma Veronica , Zeyda Maximilian , Itariu Bianca K , Langer Felix B , Prager Gerhard , Stulnig Thomas M 
Published: April 2016

AbstractBackground and AimObesity is a major risk factor for liver fibrosis and tightly associated with low levels of adiponectin. Adiponectin has antifibrogenic activity protecting from liver fibrosis, which is mainly driven by activated hepatic stellate cells (HSC). Aquaporins are transmembrane proteins that allow the movement of water and, in case of aquaglyceroporins (AQPs), of glycerol that is needed in quiescent HSC for lipogenesis. Expression of various AQPs in liver is altered by obesity; however, the mechanisms through which obesity influences HSCs activation and AQPs expression remain unclear. This study aimed to identify obesity‐associated factors that are related to HSC AQPs expression activation and lipid storage.MethodsCorrelations between serum adipokine levels and hepatic AQPs gene expression were analyzed from a cohort of obese patients. AQP and fibrotic gene expression was determined in a HSC line (LX2) and in a hepatocyte cell line (HepG2) after stimulation with adiponectin using quantitative real‐time polymerase chain reaction.ResultsWe found that serum adiponectin significantly correlated with liver AQP3, AQP7, AQP9 gene expressions. In vitro, adiponectin induced upregulation of AQP3 gene and AQP3 protein expression in human HSCs, but not in hepatocytes, while AQP7, AQP9 remained undetectable. Accordingly, HSC stimulated with adiponectin increased glycerol uptake, lipogenic gene expression, and lipid storage while downregulating activation/fibrosis markers.ConclusionsThese findings demonstrate that adiponectin is a potent inhibitor of HSC activation and induces AQPs expression. Thus, low serum levels of adiponectin could be a mechanism how obesity affects the functional state of HSC, thereby contributing to obesity‐associated liver fibrosis.