bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse effects of amphotericin B in children; a retrospective comparison of conventional and liposomal formulations
Authors: Andrew Eden C. , Curtis Nigel , Coghlan Ben , Cranswick Noel , Gwee Amanda
Published: January 2018

Aims

Lipid formulations of amphotericin B, rather than conventional amphotericin (c‐amB), are increasingly used despite limited data comparing these preparations in children. Data on the incidence of adverse effects with amphotericin B at standard doses are scarce. This study aimed to compare the adverse effects associated with standard doses of c‐amB and liposomal amphotericin (l‐amB) in children.

Methods

Children admitted to the Royal Children's Hospital Melbourne and treated with c‐amB or l‐amB between January 2010 and September 2013 were included. Clinical and laboratory data were retrospectively extracted from medical records to compare amphotericin‐related infusion reactions, nephrotoxicity (glomerulotoxicity and tubulopathy) and hepatotoxicity.

Results

Seventy‐six children received c‐amB and 39 received l‐amB. Standard drug administration (recommended dose and infusion time) occurred in 74% (56/76) of patients on c‐amB and 85% (33/39) on l‐amB. In these 89 children, infusion‐related reactions were similar for both c‐amB and l‐amB (23% (13/56) vs. 9% (3/33); P = 0.15); none occurred in children aged <90 days. There was no difference in amphotericin‐associated glomerulotoxicity (c‐amB 14% (8/56) vs. l‐amB 21% (7/33); P = 0.40) or in the median maximum potassium requirements (c‐amB 3.1 vs. l‐amB 2.3 mmol kg−1 d−1; P = 0.29). Hepatotoxicity occurred more frequently with l‐amB than c‐amB (83% (24/29) vs. 56% (20/36); P = 0.032).

Conclusions

When appropriately administered, l‐amB was associated with more hepatotoxicity than c‐amB, with no difference in infusion‐related reactions or nephrotoxicity. Differences in adverse effects between the preparations is not as marked in children as reported in adults.
Influence of pharmacogenetic polymorphisms and demographic variables on metformin pharmacokinetics in an admixed Brazilian cohort
Authors: Santoro Ana Beatriz , Botton Mariana Rodrigues , Struchiner Claudio José , Suarez‐Kurtz Guilherme
Published: January 2018

Aims

To identify pharmacogenetic and demographic variables that influence the systemic exposure to metformin in an admixed Brazilian cohort.

Methods

The extreme discordant phenotype was used to select 106 data sets from nine metformin bioequivalence trials, comprising 256 healthy adults. Eleven single‐nucleotide polymorphisms in SLC22A1, SLC22A2, SLC47A1 SLC47A2 and in transcription factor SP1 were genotyped and a validated panel of ancestry informative markers was used to estimate the individual proportions of biogeographical ancestry. Two‐step (univariate followed by multivariate) regression modelling was developed to identify covariates associated with systemic exposure to metformin, accessed by the area under the plasma concentration–time curve, between 0 and 48 h (AUC0–48h), after single oral doses of metformin (500 or 1000 mg).

Results

The individual proportions of African, Amerindian and European ancestry varied widely, as anticipated from the structure of the Brazilian population The dose‐adjusted, log‐transformed AUC0–48h's (ng h ml−1 mg−1) differed largely in the two groups at the opposite ends of the distribution histogram, namely 0.82, 0.79–0.85 and 1.08, 1.06–1.11 (mean, 95% confidence interval; P = 6.10−26, t test). Multivariate modelling revealed that metformin AUC0–48h increased with age, food and carriage of rs12208357 in SLC22A1 but was inversely associated with body surface area and individual proportions of African ancestry.

Conclusions

A pharmacogenetic marker in OCT1 (SLC22A1 rs12208357), combined with demographic covariates (age, body surface area and individual proportion of African ancestry) and a food effect explained 29.7% of the variability in metformin AUC0–48h.
How do passion for video games and needs frustration explain time spent gaming?
Authors: Mills Devin J. , Milyavskaya Marina , Mettler Jessica , Heath Nancy L. , Derevensky Jeffrey L.
Published: January 2018

Research applying self‐determination theory and the dualistic model of passion (DMP) has shown video games may satisfy basic psychological needs (i.e., competence, autonomy, and relatedness) and be identified as a passion. The DMP distinguishes between healthy or harmonious passion and problematic or obsessive passion (OP), with the latter reflecting an overreliance towards one's passion to obtain needs satisfaction. The experience of daily obstructions to needs satisfaction, or needs frustration (NF), may facilitate such an overreliance. This study explored how NF and both types of passion explain the amount of time that university students spend gaming. The overall association between NF and time spent gaming was not significant. However, for video game users with low levels of OP for gaming, there was a significant negative association between NF and time spent gaming. Additionally, evidence of a mutually reinforcing association between NF and OP for gaming indicates that a vicious cycle exists, whereby a strong OP for gaming predicts and is reinforced by greater NF. The theoretical implications are discussed.
In vivo effects of μ‐opioid receptor agonist/δ‐opioid receptor antagonist peptidomimetics following acute and repeated administration
Authors: Anand Jessica P , Kochan Kelsey E , Nastase Anthony F , Montgomery Deanna , Griggs Nicholas W , Traynor John R , Mosberg Henry I , Jutkiewicz Emily M
Published: January 2018

Background and Purpose

Agonists at μ‐opioid receptors (μ‐receptors) are used for pain management but produce adverse effects including tolerance, dependence and euphoria. The co‐administration of a μ‐receptor agonist with a δ‐opioid receptor (δ‐receptor) antagonist has been shown to produce antinociception with reduced development of some side effects. We characterized the effects of three μ‐receptor agonist/δ‐receptor antagonist peptidomimetics in vivo after acute and repeated administration to determine if this profile provides a viable alternative to traditional opioid analgesics.

Experimental Approach

Three μ‐receptor agonist / δ‐receptor antagonist peptidomimetics, AAH8, AMB46 and AMB47, and morphine were evaluated for the development of tolerance and dependence after 5 days of twice daily treatment with escalating doses of drug (10–50 mg·kg−1). Antinociceptive effects were measured in the warm water tail withdrawal assay before and after repeated drug treatment. Physical dependence was evaluated by naltrexone‐precipitated withdrawal jumping. The rewarding effects of AAH8 were evaluated using a conditioned place preference (CPP) assay with twice daily conditioning sessions performed for 5 days.

Key Results

Morphine, AAH8, AMB47 and AMB46 all demonstrated acute antinociceptive effects, but repeated administration only produced tolerance in animals treated with morphine and AMB46. Injection of naltrexone precipitated fewer jumps in mice treated repeatedly with AAH8 as compared with morphine, AMB47 or AMB46. Conditioning with morphine, but not AAH8, produced significant CPP.

Conclusions and Implications

AAH8 may be a better alternative than traditional opioid analgesics, producing antinociception with less development of tolerance and dependence and may be less rewarding than morphine.
Cambogin suppresses dextran sulphate sodium‐induced colitis by enhancing Treg cell stability and function
Authors: Lu Yue , Kim Na‐Mi , Jiang Yi‐Wen , Zhang Hong , Zheng Dan , Zhu Fu‐Xiang , Liang Rui , Li Bin , Xu Hong‐Xi
Published: January 2018

Background and Purpose

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract, and an impaired immune response plays a critical role in IBD. The current drugs and therapies for IBD treatment are of limited use, therefore, there is a need to find novel drugs or therapies for this disease. We investigated the effect of cambogin in a mouse model of dextran sulphate sodium (DSS)‐induced colitis and whether cambogin attenuates inflammation via a Treg‐cell‐mediated effect on the immune response.

Experimental Approach

Chronic colitis was established in mice using 2% DSS, and cambogin (10 mg·kg−1, p.o.) was administered for 10 days. Body weight, colon length and colon histology were assessed. Cytokine production was measured using elisa and quantitative real‐time PCR. To evaluate the mechanism of cambogin, human CD4+CD25hiCD127lo Treg cells were isolated from peripheral blood mononuclear cells. Major signalling profiles involved in Treg cell stability were measured.

Key Results

Cambogin attenuated diarrhoea, colon shortening and colon histological injury and IL‐6, IFN‐γ and TNF‐α production in DSS‐treated mice. Cambogin also up‐regulated Treg cell numbers in both the spleen and mesenteric lymph nodes. Furthermore, cambogin (10 μM) prevented Foxp3 loss in human primary Treg cells in vitro, and promoted USP7‐mediated Foxp3 deubiquitination and increased Foxp3 protein expression in LPS‐treated cells.

Conclusions and Implications

The effect of cambogin on DSS‐induced colitis is expedited by a Treg‐cell‐mediated modification of the immune response, suggesting that cambogin could be applied as a novel agent for treating colitis and other Treg cell‐related diseases.
Resolvin E1, resolvin D1 and resolvin D2 inhibit constriction of rat thoracic aorta and human pulmonary artery induced by the thromboxane mimetic U46619
Authors: Jannaway Melanie , Torrens Christopher , Warner Jane A , Sampson Anthony P
Published: January 2018

Background and Purpose

The ω‐6 fatty acid‐derived lipid mediators such as prostanoids, thromboxane and leukotrienes have well‐established roles in regulating both inflammation and smooth muscle contractility. Resolvins are derived from ω‐3 fatty acids and have important roles in promoting the resolution of inflammation, but their activity on smooth muscle contractility is unknown. We investigated whether resolvin E1 (RvE1), resolvin D1 (RvD1) and resolvin D2 (RvD2) can modulate contractions of isolated segments of rat thoracic aorta (RTA) or human pulmonary artery (HPA) induced by the α1‐adrenoceptor agonist phenylephrine or the stable thromboxane A2 mimetic U46619.

Experimental Approach

Contractile responses in RTA and HPA were measured using wire myography. Receptor expression was investigated by immunohistochemistry.

Key Results

Constriction of RTA segments by U46619, but not by phenylephrine, was significantly inhibited by pretreatment for 1 or 24 h with 10–100 nM RvE1, RvD1 or RvD2. The inhibitory effect of RvE1 was partially blocked by a chemerin receptor antagonist (CCX832). RvE1 at only 1–10 nM also significantly inhibited U46619‐induced constriction of HPA segments, and the chemerin receptor, GPR32 and FPR2/ALX were identified in HPA smooth muscle.

Conclusion and Implications

These data suggest that resolvins or their mimetics may prove useful novel therapeutics in diseases such as pulmonary arterial hypertension, which are characterized by increased thromboxane contractile activity.
Understanding intratumor heterogeneity by combining genome analysis and mathematical modeling
Authors: Niida Atsushi , Nagayama Satoshi , Miyano Satoru , Mimori Koshi
Published: January 2018

Cancer is composed of multiple cell populations with different genomes. This phenomenon called intratumor heterogeneity (ITH) is supposed to be a fundamental cause of therapeutic failure. Therefore, its principle‐level understanding is a clinically important issue. To achieve this goal, an interdisciplinary approach combining genome analysis and mathematical modeling is essential. For example, we have recently performed multiregion sequencing to unveil extensive ITH in colorectal cancer. Moreover, by employing mathematical modeling of cancer evolution, we demonstrated that it is possible that this ITH is generated by neutral evolution. In this review, we introduce recent advances in a research field related to ITH and also discuss strategies for exploiting novel findings on ITH in a clinical setting.
Bronchiolitis obliterans syndrome is associated with increased p-glycoprotein expression and loss of glucocorticoid receptor from steroid-resistant proinflammatory CD8+ T cells
Authors: Hodge G , Hodge S , Nguyen P T , Yeo A , Sarkar P , Badiei A , Holmes-Liew C L , Reynolds P N , Holmes M
Published: January 2018

Immunosuppressive therapy fails to suppress the production of proinflammatory cytokines, particularly by CD8+ T cells, in stable lung transplant recipients and those undergoing chronic rejection, suggesting that some patients may become relatively resistant to immunosuppressants such as glucocorticoids (GC). We have shown loss of GC receptor (GCR) from the CD8+ cells, and we hypothesized that the drug membrane efflux pump, p-glycoprotein-1 (Pgp), may also be involved in lymphocyte steroid resistance following lung transplant. Pgp/GCR expression and interferon (IFN)-γ/tumour necrosis factor (TNF)-α proinflammatory cytokine production was measured in blood lymphocytes from 15 stable lung transplant patients, 10 patients with bronchiolitis obliterans syndrome (BOS) and 10 healthy aged-matched controls (± prednisolone ± Pgp inhibitor, cyclosporin A ± GCR activator, Compound A) using flow cytometry. Both Pgp+ and Pgp– lymphocyte subsets from all subjects produced IFN-γ/TNF-α proinflammatory cytokines. Pgp expression was increased in CD8+Pgp+ T cells and correlated with IFN-γ/TNF-α expression and BOS grade. Reduced GCR was observed in CD8+Pgp– T, natural killer (NK) T-like and NK cells from stable patients compared with controls, and reduced further in CD8+Pgp– T cells in BOS. The addition of 2·5 ng/ml cyclosporin A and 1 µM prednisolone inhibit IFN-γ/TNF-α production significantly by CD8+Pgp+ T cells from BOS patients. The addition of 10 µM Compound A and 1 µM prednisolone inhibit IFN-γ/TNF-α production significantly by CD8+Pgp– T cells from BOS patients. BOS is associated with increased Pgp expression and loss of GCR from steroid-resistant proinflammatory CD8+ T cells. Treatments that inhibit Pgp and up-regulate GCR in CD8+ T cells may improve graft survival.
Research review: Aging out of residential care in South Africa
Authors: van Breda Adrian D.
Published: January 2018

Approximately 21,000 children were accommodated in residential care in South Africa in 2011/2012. Despite this large number, and the state's substantial financial investment in residential care, there has, until recently, been little research on care‐leaving: the transition out of care due to reaching adulthood. Furthermore, much of the research available has not been published in international journals. This article reports on a systematic review of research on residential care‐leaving in South Africa, from 2003 to 2016. A thematic analysis of the resulting 40 research outputs maps the scope of findings from South African research, in relation to theory of leaving care, measurement tools developed, young people's experiences of leaving care, transitional outcomes, processes of leaving care, facilitators of improved outcomes, care‐leaving services, and policy on leaving care. Critical gaps in the current research opus are identified, with a view to refining future research on young people aging out of care in South Africa.
Mothering after child removal: Living under the rule of Greek gods
Authors: Honey Anne , Mayes Rachel , Miceli Melissa
Published: January 2018

Many women who experience mental illness are mothers. Evidence suggests that the role of mother is of great importance and value to these women, yet they are more likely than other women to have their children removed from their care. Little is known about the experiences of these mothers after their children are removed. This paper presents a phenomenological analysis of in‐depth interviews with 8 women to answer the following question: How do mothers living with severe mental illness experience mothering after removal of their children by child protection services? The analysis showed that mothering continued to be a major life role for these women, but the way they enacted this role was transformed. Their mothering was now constrained and prescribed by external agents, likened to Greek gods, which imposed both boundaries to what they could do and an obligation to prove themselves worthy. Like Greek gods, these external agents were seen as all powerful, unpredictable, and flawed. The study highlights the need for child protection services and support services to recognize and support noncustodial mothering activities.
WNT10B mutations associated with isolated dental anomalies
Authors: Kantaputra P.N. , Hutsadaloi A. , Kaewgahya M. , Intachai W. , German R. , Koparal M. , Leethanakul C. , Tolun A. , Ketudat Cairns J.R.
Published: January 2018

Isolated hypodontia is the most common human malformation. It is caused by heterozygous variants in various genes, with heterozygous WNT10A variants being the most common cause. WNT10A and WNT10B are paralogs that likely evolved from a common ancestral gene after its duplication. Recently, an association of WNT10B variants with oligodontia (severe tooth agenesis) has been reported. We performed mutational analysis in our cohort of 256 unrelated Thai families with various kinds of isolated dental anomalies. In 7 families afflicted with dental anomalies we detected 4 heterozygous missense variants in WNT10B. We performed whole exome sequencing in the patients who had WNT10B mutations and found no mutations in other known hypodontia‐associated genes, including WNT10A, MSX1, PAX9, EDA, AXIN2, EDAR, EDARADD, LPR6, TFAP2B, LPR6, NEMO, KRT17, and GREM2. Our findings indicate that the variants c.475G>C [p.(Ala159Pro)], found in 4 families, and c.1052G>A [p.(Arg351His)], found in 1 family, are most probably causative. They also show that WNT10B variants are associated not only with oligodontia and isolated tooth agenesis, but also with microdontia, short tooth roots, dental pulp stones, and taurodontism.
Nafamostat mesilate attenuates inflammation and apoptosis and promotes locomotor recovery after spinal cord injury
Authors: Duan Hui‐Quan , Wu Qiu‐Li , Yao Xue , Fan Bao‐You , Shi Hong‐Yu , Zhao Chen‐Xi , Zhang Yan , Li Bo , Sun Chao , Kong Xiao‐Hong , Zhou Xin‐Fu , Feng Shi‐Qing
Published: January 2018

Aim

Spinal cord injury (SCI) leads to severe neural damage for which there is currently no effective treatment. Exploration of the neuroprotective effect among clinically approved drugs will speed up clinical translation of SCI. Nafamostat mesilate (NM) as a synthetic serine protease inhibitor has been used clinically in pancreatitis treatments. However, its effectiveness in SCI is unknown. The aim of this study was to confirm the efficacy of NM in ameliorating SCI.

Methods

Intraperitoneal administration of NM was performed on a contusion SCI model in Wistar rat. Hematoxylin and eosin staining (H&E staining) and Luxol fast blue (LFB) staining were used to observe the histological lesions. Apoptosis was examined by TUNEL staining, Annexin V‐FITC/PI, caspase‐3, and Bcl‐2. Cytokines and neurotrophins were tested by Western blot. Locomotion recovery assessed by hindlimb BBB score and the inclined plane test.

Results

Nafamostat mesilate treatment significantly improved locomotion recovery as assessed by hindlimb BBB scores and the inclined plane test. H&E staining and LFB staining showed a significant increase in spared tissue in both gray matter and white matter. NM decreased the expression of the proinflammatory cytokines TNF‐α and IL‐6. In addition, apoptosis was also significantly decreased, as shown by TUNEL staining and Annexin V‐FITC/PI and by Western blotting for caspase‐3 and Bcl‐2 expression. Due to the mechanism of action of NM as a serine protease inhibitor, the drug decreased thrombin expression in the damaged spinal cord. Furthermore, NM increased the expression of neurotrophins (NT‐3, BDNF, and NGF).

Conclusions

Upon NM treatment, the functional and histological outcomes were improved, and microenvironment upon SCI was modulated. As a clinically approved drug, NM holds promise for clinical use after spinal cord injury.
Ropivacaine preperitoneal wound infusion for pain relief and prevention of incisional hyperalgesia after laparoscopic colorectal surgery: a randomized, triple‐arm, double‐blind controlled evaluation vs intravenous lidocaine infusion, the CATCH study
Authors: Beaussier M. , Parc Y. , Guechot J. , Cachanado M. , Rousseau A. , Lescot T. ,   the CATCH Study Investigators
Published: January 2018

Aim

The abdominal incision for specimen extraction could trigger postoperative pain after laparoscopic colorectal resections (LCRs). Continuous wound infusion (CWI) of ropivacaine may be a valuable option for postoperative analgesia. This study was undertaken to evaluate the potential benefits of ropivacaine CWI on pain relief, metabolic stress reaction, prevention of wound hyperalgesia and residual incisional pain after LCR. A subgroup with intravenous lidocaine infusion (IVL) was added to discriminate between the peripheral and systemic effects of local anaesthetic infusions.

Method

Patients were randomly allocated to three subgroups: CWI (0.2% ropivacaine 10 ml/h for 48 h); IVL (lidocaine 1.5% at 4 ml/h for 48 h); control group.

Results

In all, 95 patients were randomized (86 patients analysed). Postoperative pain intensity did not differ significantly between groups. Within the first 24 h after surgery, morphine requirement was significantly lower in the CWI group compared with the IVL group, but there was no significant difference compared with the control group (P = 0.02 and P = 0.15, respectively). The area of hyperalgesia did not differ significantly between subgroups, nor did the hyperalgesia ratio which was 1.2 cm (0.0−6.7) vs 1.9 cm (0.4−4.0) vs 2.0 cm (0.5−7.0) in the CWI, IVL and control groups respectively (P = 0.35). The number of patients reporting residual incisional pain after 3 months (3/26 vs 4/23 vs 4/23 in the CWI, IVL and control groups respectively) did not differ significantly between the groups, nor did their metabolic stress reactions.

Conclusion

Ropivacaine CWI at the site of the abdominal incision did not provide any significant benefit either on analgesia or on the prevention of wound hyperalgesia after LCR.
Microcystic adnexal carcinoma with sebaceous differentiation: Three cases
Authors: Fernandez‐Flores Angel , Llamas‐Velasco Mar , Saus Carles , Patel Anisha , Rutten Arno
Published: January 2018

Microcystic adnexal carcinoma (MAC) is a low‐grade malignant tumor of the skin. Histologically, this tumor shows a biphasic pattern, with cords and nests of basaloid cells, as well as keratin horn cysts. This biphasic histological appearance has been interpreted by some authors as a sign of double eccrine and folliculosebaceous‐apocrine differentiation, whereas some other authors defend a solely eccrine differentiation. In this context, sebaceous differentiation in MAC would support the first option. However, there are only 3 cases of MAC with sebaceous differentiation in the literature, and all of them were reported before adipophilin was available, which in the appropriate context (eg, testing clear cells for sebaceous vs eccrine differentiation) is very useful. In this study, we present 3 cases of MAC with focal sebaceous differentiation confirmed by immunoexpression of adipophilin in the sebaceous foci.
Morbid obesity and type 2 diabetes alter intestinal fatty acid uptake and blood flow
Authors: Koffert Jukka , Ståhle Mia , Karlsson Henry , Iozzo Patricia , Salminen Paulina , Roivainen Anne , Nuutila Pirjo
Published: January 2018

Aims

Bariatric surgery is the most effective treatment to tackle morbid obesity and type 2 diabetes, but the mechanisms of action are still unclear. The objective of this study was to investigate the effects of bariatric surgery on intestinal fatty acid (FA) uptake and blood flow.

Materials and Methods

We recruited 27 morbidly obese subjects, of whom 10 had type 2 diabetes and 15 were healthy age‐matched controls. Intestinal blood flow and fatty acid uptake from circulation were measured during fasting state using positron emission tomography (PET). Obese subjects were re‐studied 6 months after bariatric surgery. The mucosal location of intestinal FA retention was verified in insulin resistant mice with autoradiography.

Results

Compared to lean subjects, morbidly obese subjects had higher duodenal and jejunal FA uptake (P < .001) but similar intestinal blood flow (NS). Within 6 months after bariatric surgery, obese subjects had lost 24% of their weight and 7/10 diabetic subjects were in remission. Jejunal FA uptake was further increased (P < .03). Conversely, bariatric surgery provoked a decrease in jejunal blood flow (P < .05) while duodenal blood flow was preserved. Animal studies showed that FAs were taken up into enterocytes, for the most part, but were also transferred, in part, into the lumen.

Conclusions

In the obese, the small intestine actively takes up FAs from circulation and FA uptake remains higher than in controls post‐operatively. Intestinal blood flow was not enhanced before or after bariatric surgery, suggesting that enhanced intestinal FA metabolism is not driven by intestinal perfusion.
A multi‐ingredient athletic supplement disproportionately enhances hind leg musculature, jumping performance, and spontaneous locomotion in crickets (Acheta domesticus)
Authors: Tran Jonathan , Aksenov Vadim , Rollo C. David
Published: January 2018

Nutrition is a key component of life‐history theory with profound impacts on fitness traits. We examined lifetime impacts of a multi‐ingredient athletic supplement (MAS) on physical performance, anatomical morphology, survivorship, and general life‐history features in the house cricket,Acheta domesticus(L.) (Orthoptera: Gryllidae). TheMASwas formulated using 13 nutraceutical supplements that are commonly used by human athletes specifically to improve athletic performance. Cricket doses were based on human doses adjusted for body size and metabolic rate. Markers of athletic performance included: jumping distance, spontaneous locomotor activity, and morphology of the hind legs (femurs). Supplemented adult crickets jumped ca. 25% further and expressed elevated spontaneous locomotion relative to controls. TheMASdisproportionately increased hind leg femur length and width. Life‐history endpoints included survivorship, juvenile growth rate, maturation age, and mature body size. Supplemented crickets showed faster juvenile growth and earlier maturation, but no change in final adult size. A 20% increase in mean survivorship (extending into older ages) was also documented. Crickets represent an excellent new model for assessing athletic diets and associated performance criteria. Finally, as experimental animals were untrained, we argue that our supplement may represent a novel ‘exercise mimetic’ that impacts both performance and survivorship.
ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis
Authors: Montalban X. , Gold R. , Thompson A. J. , Otero‐Romero S. , Amato M. P. , Chandraratna D. , Clanet M. , Comi G. , Derfuss T. , Fazekas F. , Hartung H. P. , Havrdova E. , Hemmer B. , Kappos L. , Liblau R. , Lubetzki C. , Marcus E. , Miller D. H. , Olsson T. , Pilling S. , Selmaj K. , Siva A. , Sorensen P. S. , Sormani M. P. , Thalheim C. , Wiendl H. , Zipp F.
Published: January 2018

Background and purpose

Multiple sclerosis (MS) is a complex disease with new drugs becoming available in the past years. There is therefore a need for a reference tool compiling current data to aid professionals in treatment decisions. The objective was to develop an evidence‐based clinical practice guideline for the pharmacological treatment of people with MS.

Methods

This guideline has been developed using the GRADE methodology and following the updated EAN recommendations for guideline development. Clinical questions were formulated in PICO format (patient, intervention, comparator, outcome) and outcomes were prioritized according to their relevance to clinical practice. Literature searches up to December 2016 were performed and the evidence is presented narratively and, when possible, combined in a meta‐analysis. The quality of evidence was rated into four categories – very high, high, low and very low − according to the risk of bias. The recommendations with assigned strength (strong, weak) were formulated based on the quality of evidence and the risk−benefit balance. Consensus between the panelists was reached by use of the modified nominal group technique.

Results

A total of 10 questions have been agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease‐modifying drugs approved by the European Medicine Agency at the time of publication. A total of 21 recommendations were agreed by the guideline working group members after three rounds of consensus.

Conclusion

The present guideline, which includes descriptions of the evidence together with recommendations, will enable homogeneity of treatment decisions across Europe.
Logging disturbance shifts net primary productivity and its allocation in Bornean tropical forests
Authors: Riutta Terhi , Malhi Yadvinder , Kho Lip Khoon , Marthews Toby R. , Huaraca Huasco Walter , Khoo MinSheng , Tan Sylvester , Turner Edgar , Reynolds Glen , Both Sabine , Burslem David F.R.P. , Teh Yit Arn , Vairappan Charles S. , Majalap Noreen , Ewers Robert M.
Published: January 2018

Tropical forests play a major role in the carbon cycle of the terrestrial biosphere. Recent field studies have provided detailed descriptions of the carbon cycle of mature tropical forests, but logged or secondary forests have received much less attention. Here, we report the first measures of total net primary productivity (NPP) and its allocation along a disturbance gradient from old‐growth forests to moderately and heavily logged forests in Malaysian Borneo. We measured the main NPP components (woody, fine root and canopy NPP) in old‐growth (n = 6) and logged (n = 5) 1 ha forest plots. Overall, the total NPP did not differ between old‐growth and logged forest (13.5 ± 0.5 and 15.7 ± 1.5 Mg C ha−1 year−1 respectively). However, logged forests allocated significantly higher fraction into woody NPP at the expense of the canopy NPP (42% and 48% into woody and canopy NPP, respectively, in old‐growth forest vs 66% and 23% in logged forest). When controlling for local stand structure, NPP in logged forest stands was 41% higher, and woody NPP was 150% higher than in old‐growth stands with similar basal area, but this was offset by structure effects (higher gap frequency and absence of large trees in logged forest). This pattern was not driven by species turnover: the average woody NPP of all species groups within logged forest (pioneers, nonpioneers, species unique to logged plots and species shared with old‐growth plots) was similar. Hence, below a threshold of very heavy disturbance, logged forests can exhibit higher NPP and higher allocation to wood; such shifts in carbon cycling persist for decades after the logging event. Given that the majority of tropical forest biome has experienced some degree of logging, our results demonstrate that logging can cause substantial shifts in carbon production and allocation in tropical forests.
Evapotranspiration model comparison and an estimate of field scaleMiscanthuscanopy precipitation interception
Authors: Holder Amanda J. , McCalmont Jon P. , McNamara Niall P. , Rowe Rebecca , Donnison Iain S.
Published: January 2018

The bioenergy cropMiscanthus × giganteushas a high water demand to quickly increase biomass with rapid canopy closure and effective rainfall interception, traits that are likely to impact on hydrology in land use change. Evapotranspiration (ET, the combination of plant and ground surface transpiration and evaporation) forms an important part of the water balance, and fewETmodels have been tested withMiscanthus. Therefore, this study uses field measurements to determine the most accurateETmodel and to establish the interception of precipitation by the canopy (Ci). DailyETestimates from 2012 to 2016 using the Hargreaves–Samani, Priestley–Taylor, Granger–Gray, and Penman–Monteith (short grass) models were calculated using data from a weather station situated in a 6 haMiscanthuscrop. Results from these models were compared to data from on‐site eddy covariance (EC) instrumentation to determine accuracy and calculate the crop coefficient (Kc) model parameter. Ciwas measured from June 2016 to March 2017 using stem‐flow and through‐flow gauges within the crop and rain gauges outside the crop. The closest estimatedETto theECdata was the Penman‐Monteith (short grass) model. TheKcvalues proposed are 0.63 for the early season (March and April), 0.85 for the main growing season (May to September), 1.57 for the late growing season (October and November), and 1.12 over the winter (December to February). These more accurateKcvalues will enable betterETestimates with the use of the Penman‐Monteith (short grass) model improving estimates of potential yields and hydrological impacts of land use change. Ciwas 24% and remained high during the autumn and winter thereby sustaining significant levels of canopy evaporation and suggesting benefits for winter flood mitigation.
Sexualized drug use (‘chemsex’) and high‐risk sexual behaviours in HIV‐positive men who have sex with men
Authors: Pufall EL , Kall M , Shahmanesh M , Nardone A , Gilson R , Delpech V , Ward H ,   The Positive Voices study group
Published: January 2018

Objectives

The incidence of sexually transmitted infections (STIs) and HIV infection remains high in gay, bisexual, and other men who have sex with men (MSM) in the UK, and sexualized drug use (“chemsex”) and injecting drug use (“slamsex”) may play a part in this. We aimed to characterize HIV‐positive MSM engaging in chemsex/slamsex and to assess the associations with self‐reported STI diagnoses and sexual behaviours.

Methods

Data from a 2014 survey of people attending HIV clinics in England and Wales were linked to clinical data from national HIV surveillance records and weighted to be nationally representative. Multivariable logistic regression assessed the associations of chemsex and slamsex with self‐reported unprotected anal intercourse (UAI), serodiscordant UAI (sdUAI) (i.e. UAI with an HIV‐negative or unknown HIV status partner), sdUAI with a detectable viral load (>50 HIV‐1 RNA copies/mL), hepatitis C, and bacterial STIs.

Results

In the previous year, 29.5% of 392 sexually active participants engaged in chemsex, and 10.1% in slamsex. Chemsex was significantly associated with increased odds of UAI [adjusted odds ratio (AOR) 5.73; P < 0.001], sdUAI (AOR 2.34; P < 0.05), sdUAI with a detectable viral load (AOR 3.86; P < 0.01), hepatitis C (AOR 6.58; P < 0.01), and bacterial STI diagnosis (AOR 2.65; P < 0.01). Slamsex was associated with increased odds of UAI (AOR 6.11; P < 0.05), hepatitis C (AOR 9.39; P < 0.001), and bacterial STI diagnosis (AOR 6.11; P < 0.001).

Conclusions

Three in ten sexually active HIV‐positive MSM engaged in chemsex in the past year, which was positively associated with self‐reported depression/anxiety, smoking, nonsexual drug use, risky sexual behaviours, STIs, and hepatitis C. Chemsex may therefore play a role in the ongoing HIV and STI epidemics in the UK.
Concentration‐dependent effect of bleaching agents on the immunolabelling of interleukin‐6, interleukin‐17 and CD5‐positive cells in the dental pulp
Authors: Benetti F. , Gomes‐Filho J. E. , Ferreira L. L. , Sivieri‐Araújo G. , Ervolino E. , Briso A. L. F. , Cintra L. T. A.
Published: January 2018

Aim

To evaluate lymphocyte‐like cell activation (CD5‐positive cells) and the expression of interleukin (IL)‐6 and IL‐17 in the pulp after tooth bleaching with two concentrations of hydrogen peroxide (H2O2).

Methodology

The right and left maxillary molars from 40 rats were treated randomly with bleaching gel with 20% H2O2 (BLUE group, 1 application of 50 min), 35% H2O2 (MAXX group, three applications of 15 min), or placebo gel (control). After 2 and 30 days, the rats were killed (n = 10), and the jaws were processed for histological and immunohistochemistry analysis of the pulp tissue. The scores of inflammation and immunolabelling (IL‐6/IL‐17) were submitted to Mann–Whitney and Kruskal–Wallis followed Dunn tests, respectively; anova tests were used for comparisons of number of CD5‐positive cells and pulp chamber area values (P < 0.05).

Results

At 2 days, 60% of specimens of the BLUE group were associated with moderate inflammation in pulp horns, and in the MAXX group with necrosis (P < 0.05). At 30 days, the pulp was organized, and tertiary dentine was formed. The MAXX group had superior immunolabelling of IL‐17 at 2 days differing significantly from other groups (P < 0.05). At 2 days, 90% of the specimens of the BLUE group had moderate immunolabelling of IL‐6, and 50% of the MAXX group had severe immunolabelling, both significantly different from the control (P < 0.05). There was no significant difference between the groups at 30 days (P > 0.05). CD5‐positive cells were present at 2 and 30 days, particularly in the bleached groups (P < 0.05), without significant difference between time periods (P > 0.05).

Conclusions

IL‐6 and IL‐17 participated in inflammation in the pulp tissue of rats after tooth bleaching, particularly at 2 days. The immunolabelling was greater with increasing H2O2 concentration. This process was accompanied by the prolonged activation of CD5‐positive cells.
Cordierite thermal insulation materials reinforced by aluminosilicate fiber/mullite whiskers hierarchical structure
Authors: Qin Meng Li , Wang Xi Tang , Wang Zhou Fu , Ma Yan , Liu Hao
Published: January 2018

Cordierite thermal insulation materials were prepared via a starch consolidation casting (SCC) technique, using kyanite, MgO and SiO2 as raw materials. Aluminosilicate ceramic fiber were used as the substrate for in situ synthesized mullite whiskers. The mullite whiskers grew in situ on the surface of the aluminosilicate ceramic fiber via AlF3 and were interspersed among the cordierite crystalline. The as‐prepared cordierite materials reinforced by the aluminosilicate ceramic fiber/mullite whiskers hierarchical structure had a relatively high cold modulus strength and cold compression strength. Moreover, the thermal conductivity of the materials was as low as 0.329 W/(m K) (RT‐1000°C). We propose a growing mechanism of mullite whiskers on the surface of the aluminosilicate ceramic fiber.
Religious identity, community and religious minorities’ search efforts for religiously sanctioned food: The case of halal food in non‐Muslim majority markets
Authors: Mumuni Alhassan G. , Veeck Ann , Luqmani Mushtaq , Quraeshi Zahir A. , Kamarulzaman Yusniza
Published: January 2018

This research introduces the concept of search effort to explore the drivers of
religion‐motivated
consumption by religious minorities. The study draws on three theoretical frameworks to develop a model and hypotheses about the role of religious identity, community, knowledge and attitudes in explaining the effort religious minorities exert to uphold religiously motivated consumption behaviour. Using the search for halal food in the United States as a research context and data from a survey of U.S. consumers to test a model of search effort, the study finds that insistence on religiously motivated behaviour is a strong predictor of consumers’ willingness to exert effort towards the behaviour. In turn, degree of religiosity, attitude towards the behaviour and religious
self‐identity
are strong positive predictors of the level of insistence. Further, religious knowledge and sense of religious community are strong positive determinants of attitude towards the behaviour. The model provides an improved conceptualization of the relationship between religious identity and consumer behaviour, particularly religiously sanctioned or motivated consumption. Theory and research implications are outlined and potential avenues for further exploration are identified.
Consumers’ perceptions of GM‐free labelled foods: A sensory experiment
Authors: Schouteten Joachim J. , Gellynck Xavier , De Steur Hans
Published: January 2018

As of today, the views of European consumers and policy makers on GM foods are still divided. While only few GM labelled foods (‘does contain’) have entered the market, GM‐free labelling (‘does not contain’) is increasingly introduced in many EU member states. This study aims to examine whether GM‐free labelling affects consumers’ sensory profiling, emotional conceptualizations and overall liking. Based on a within‐subjects experimental design, 126 Belgian subjects evaluated GM‐free and nonlabelled samples of three food products: yogurt, traditional biscuit (‘speculoos’) and crisps. The results show that overall liking did not differ significantly according to label (no vs. GM‐free), regardless of participants’ knowledge of, or attitude towards GMOs. Furthermore, regarding the impact of GM‐free labelling on consumers’ subjective taste perceptions and emotional profiling, few significant differences were reported for crisps and traditional biscuit. Regarding the latter, less positive and more negative emotional terms have been assigned to the GM‐free labelled sample. The findings of this study should be viewed in the context of the stringent EU mandatory GM food labelling policy, which led to an increase of GM‐free rather than GM labels. Future research is needed to further underpin these findings and examine differently framed labels in various settings.
Nonclassical monocytes: are they the next therapeutic targets in multiple sclerosis?
Authors: Ajami Bahareh , Steinman Lawrence
Published: January 2018

See also: Original Article by Gjelstrup et al.
Preparation and photoluminescence enhancement of Au nanoparticles embedded LaPO4:Eu3+ inverse opals
Authors: Chai Zhuangzhuang , Yang Zhengwen , Huang Anjun , Yu Chengye , Qiu Jianbei , Song Zhiguo
Published: January 2018

In this work, we present a facile preparation approach of Au nanoparticles embedded LaPO4:Eu3+ inverse opal photonic crystals. In the typical preparation process, the transparent LaPO4:Eu3+ sol including HAuCI4 was infiltrated into the opal templates. After the sintering, the 10‐20 nm Au nanoparticles were formed in the interior of nano‐sized wall of LaPO4:Eu3+ inverse opal and the Au nanoparticles embedded LaPO4:Eu3+ inverse opals were obtained. The luminescence of Au nanoparticles embedded LaPO4:Eu3+ inverse opal was investigated. The emission peaks located at the 593 (5D0→7F1), 618 (5D0→7F2) and 698 nm (5D0→7F4) from Eu3+ ions were observed. The 593, 618, and 698 nm emissions of Au nanoparticles embedded LaPO4:Eu3+ inverse opals were enhanced in contrast to these of LaPO4:Eu3+ inverse opal without the Au nanoparticles, which is from the excitation field enhancement caused by the localized surface plasmon resonance of Au nanoparticles.
Improvement of self‐activated luminescence from introduced cation disorder in Sr6V2O11
Authors: Mi Longqing , Huang Yanlin , Liu Xuanxuan , Qin Lin , Seo Hyo Jin
Published: January 2018

Adjusting the elemental composition of a host is regarded to be an effective strategy to tune its luminescent properties such as peak energy, emission efficiency, and bandwidth. In this work, the cation substitution of (Ba2+ → Sr2+) in self‐activated Sr6V2O11 was conducted to investigate the luminescence modification. All the phosphors of Sr6‐6xBa6xV2O11 (x = 0, 0.1, 0.2, 0.3, 0.4, 0.5) were synthesized by the traditional chemical sol‐gel method. The morphological properties were measured through scanning electron microscope and energy dispersive spectrum measurements. The cation substitution brings out the disorder in the structure, which exerts modifications on the luminescence properties of Sr6V2O11. The luminescence intensity and corresponding decay lifetime were enhanced with the cation disorder in the self‐activated phosphor. Cation disorder in a phosphor lattice could be one of the effective approaches to improve the luminescence efficiency.
Hierarchical growth of BiOCl on SrO‐Bi2O3‐B2O3 glass‐ceramics for self‐cleaning applications
Authors: Singh Vinay P. , Vaish Rahul
Published: January 2018

We have grown hierarchical structure of bismuth oxycloride (BiOCl) on SrO‐Bi2O3‐B2O3 (SBBO) transparent glass‐ceramic. SBBO glass‐ceramics were fabricated via conventional melt‐quenching technique while BiOCl was grown by etching the glass via HCl. Enhanced visible light driven photocatalytic activity and increasing hydrophobic feature were observed on BiOCl grown SBBO than as‐quenched SBBO glass‐ceramics. Contact angle analysis showed maximum contact angle of 130.7° on the surface of most BiOCl grown SBBO glass‐ceramic. Furthermore, under visible light illumination water contact angle decreased from 130.7° to 30.8°. Such photo‐induced hydrophilicity and catalytic performance in translucent glass‐ceramics lead self‐cleaning applications.
Effects of catalysts on polymerization and microstructure of sol‐gel derived bioglasses
Authors: Ben‐Arfa Basam A. E. , Fernandes Hugo R. , Salvado Isabel M. M. , Ferreira José M. F. , Pullar Robert C.
Published: January 2018

This work investigates the effects of the type and concentration of acid catalysts on the microstructural features of silica‐rich bioactive glasses (75Si–16Ca–5Na–4P, in mol%) synthesized from acetate and nitrate precursor salts, using an innovative rapid sol‐gel method, followed by thermal stabilization at 550°C. The results of XRD, SEM, Fourier Transform Infrared Spectrometer (FTIR) and solid state MAS NMR analysis revealed that the lower degrees of polymerization and network connectivity were found for bioglass powders obtained in the presence of high acid concentrations. A low amount of citric acid gave a polymerization degree similar to that obtained in the absence of any catalyst, but the synthesis time was as short as that found for high acid concentrations. The XRD and FTIR results demonstrated amorphous glass powders free of any nitrate by‐products. The microstructure and degree of polymerization could be modified by changing the type and concentration of acid catalyst, enabling one to tailor the bioactivity of glasses even without changing the starting composition.
Consumer Boycotts as Instruments for Structural Change
Authors: Beck Valentin
Published: January 2018

Consumer boycotts have become a frequent form of social protest in the digital age. The corporate malpractices motivating them are varied, including environmental pollution, lack of minimum labour standards, severe mistreatment of animals, lobbying and misinformation campaigns, collaboration or complicity with illegitimate political regimes, and systematic tax evasion and tax fraud. In this article, I argue that organised consumer boycotts should be regarded as a legitimate and purposeful instrument for structural change, provided they conform to a number of normative criteria. In order to show this, the practice and empirical context of consumer boycotts are first outlined. I then lay out and refute three general objections to this practice. Although each of these objections fails, their discussion generates insights concerning the normative standards with which boycotters must comply if they want their campaigns to be both legitimate and successful. These normative criteria are detailed along the lines of two guiding principles, proportionality and transparency. In the final step, I elaborate on structural change as the deeper purpose of consumer boycotts.