bluuebunny/crossref_metadata_2025 huggingface dataset:
Four‐port bimanual 23‐gauge vitrectomy for diabetic tractional retinal detachment
Authors: Wang Zhao‐yang , Zhao Ke‐ke , Li Jia‐kai , Rossmiller Brian , Zhao Pei‐quan
Published: February 2016

Purpose

Four‐port bimanual vitrectomy is a surgical technique that facilitates removal of epiretinal membranes in severe proliferative diabetic retinopathy (PDR). As the illumination is held by the assistant through the fourth scleral incision, fibrovascular membranes are removed by bimanual manipulation techniques. The objective of this study was to evaluate the safety and efficacy of four‐port bimanual 23‐gauge vitrectomy for patients with tractional retinal detachment (TRD) in severe PDR.

Design

Retrospective, comparative, consecutive, interventional case series.

Methods

Sixty‐six eyes of 58 consecutive patients who underwent primary vitrectomy for severe diabetic TRD. Thirty‐six eyes of 31 cases that were treated with four‐port 23‐gauge vitrectomy were compared with 30 eyes of 27 cases that were treated with 23‐gauge pars plana vitrectomy (PPV). Main outcome measures were best‐corrected visual acuity (BCVA), retinal status, intraocular pressure, and incidence of intraoperative and postoperative complications with at least 6 months of follow‐up.

Results

The primary and ultimate anatomic success rates (94.4% versus 93.3%, and 100% in both groups, respectively) and the mean BCVA changes did not differ significantly between groups. The whole surgical time and the membrane removal time were significantly (p < 0.001, respectively) shorter in the four‐port 23‐gauge group than in the 23‐gauge group. There was no difference in the incidence of intraoperative and postoperative complications in both groups.

Conclusions

Four‐port bimanual 23‐gauge vitrectomy offers comparable anatomic success and shortens the surgical time compared with conventional 23‐gauge PPV in patients with TRD resulting from severe PDR.
Marginally low birthweight increases the risk of underweight and short stature at three and a half years of age
Authors: Berglund Staffan K. , Kriström Berit , Björn Matias , Lindberg Josefine , Westrup Björn , Norman Mikael , Domellöf Magnus
Published: February 2016

Aim

Little is known about the long‐term health of marginally low birthweight (LBW) children. This study characterised growth among infants weighing 2000 g–2500 g and explored the prevalence and predictors of sustained growth restriction.

Method

This prospective observational trial followed the weight and height of 281 Swedish marginally LBW children from birth to 3.5 years of age. Children with a standard deviation score (SDS) for body mass index or height below −2 were considered underweight and short, respectively.

Results

The mean SDS for weight and height showed a rapid increase before 12–19 weeks of age. The most rapid weight gain was in infants born small for gestational age. However, at 3.5 years of age, 9.5% of the children remained underweight and 6.5% had short stature. Regression models showed that slow weight gain before 19 weeks of age was the strongest predictor for lasting underweight, while slow height gain before 19 weeks of age and male sex were associated with short stature.

Conclusion

Marginally LBW infants were more likely to be underweight and have a short stature at 3.5 years of age and the absence of catch‐up growth during the first five months after birth identified those at highest risk.
STATE OWNED ENTERPRISES AS INSTRUMENTS OF INNOVATION POLICY
Authors: TÕNURIST Piret , KARO Erkki
Published: February 2016

This article expands the literature on the rationales and governance of state owned enterprises (SOEs). We show that SOEs could be seen as instruments of innovation policies and change agents within broader innovation systems that can overcome many of the conventional challenges of innovation policy and its implementation, from coordination and implementation of policies and innovation system actor networks to financing innovation. We review the existing literature on the rationales of SOEs and extend it to include innovation as a central rationale. Thereafter we provide a taxonomy that reveals the necessary policy and managerial conditions and constraints for using SOEs as instruments of innovation policy. We place some of the better‐known innovation‐oriented SOE successes and failures into this taxonomy and show that this approach will allow in future research to explore different SOE practices and potential for using SOEs as innovation policy instruments across countries.
MODELLING SOCIAL ENTERPRISES
Authors: SZYMAŃSKA Aleksandra , JEGERS Marc
Published: February 2016

The majority of research concentrates exclusively on the objectives of governments, profit entities or non‐profit organizations, while a significant number of organizations are hybrids. One form of these hybrids is the social enterprise. This paper theoretically describes social enterprises taking into consideration their main aims. Based on the ‘earned income’ school of thought, the principal‐agent theory and considering the nature of social enterprises’ activities we propose the objective functions of their owners (principals) and managers (agents). The maximization problem of the social enterprise is defined as the weighted average of the utilities of two groups of stakeholders who have an influence on the degree of the realization of the social mission and business orientations. We point out the direction which social enterprises should follow in order to obtain the highest value of their objective functions. The desired state for social enterprises should be one in which they reinvest all surpluses in the process of their mission realization and their profit is slightly higher than the required level by the principal's contract.
Coding region variant 186H/R in Exon 4 of APOBEC3G among individuals of Western India
Authors: Singh HariOm , Marathe Shruti , Nain Sumitra , Nema Vijay , Angadi Mansa , Bapat Shradha , Pawar Jyoti , Ghate Manisha , Sahay Seema , Gangakhedkar Raman R.
Published: February 2016

The allelic variations in the AIDS restriction genes have been associated with the acquisition of HIV‐1 and its progression. The distribution of antiviral gene variants significantly differs between populations. Therefore, we aimed to evaluate the distribution of variant allele of 186H/R in exon4 of APOBEC3G between HIV infected individuals and healthy controls among western Indian.In the present cross‐sectional study, we enrolled a total of 153 HIV‐infected patients confirmed and 156 unrelated healthy individuals. Polymorphism for 186H/R in exon4 of APOBEC3G gene was genotyped by PCR‐RFLP. With the frequency of 186HR heterozygous genotype of APOBEC3G was found to be 13% in healthy controls and none in HIV infected cases. The frequency of 186HH common genotype of APOBEC3G was observed higher in HIV infected individuals compared with healthy controls (100% vs 91.7%). The variant genotype 186RR in APOBEC3G was not found in both the groups. The frequency of 186R allele of APOBEC3G was found 4.16% in healthy controls and nil in HIV‐infected cases. The frequency of 186H allele of APOBEC3G was found to be higher in HIV‐infected cases compared with healthy controls (100% vs 95.83%). The frequency of 186R allele in exon4 of APOBEC3G was found to be 4.16% in healthy controls. This observation differs from the previous report published from North India stating the absence of 186R allele of APOBEC3G in the North Indian individuals. The variant 186H/R in exon4 of APOBEC3G was neither associated with risk of acquisition of HIV‐1 nor its progression.
Quantitative and semi‐quantitative histopathological examination of renal biopsies in healthy individuals, and associations with kidney function
Authors: Bar Yael , Barregard Lars , Sallsten Gerd , Wallin Maria , Mölne Johan
Published: February 2016

This study assesed the prevalence of histopathological changes in renal biopsies from healthy individuals, and the association with age, sex and smoking. Donor biopsies from 109 subjects were obtained from living kidney donors, and blood and urine samples were collected together with medical history. All biopsies were scored according to the Banff ‘97 classification with some modifications. The parameters included in this study were tubular atrophy, interstitial fibrosis, glomerulosclerosis, arteriosclerosis, arteriolohyalinosis and a sclerosis score. An alternative scoring system for tubular atrophy was examined (using ≤5% rather than <1% as a cut‐off for grade 0). Glomerular filtration rate was measured in most cases as chromium ethylenediaminetetra‐acetic acid (Cr‐EDTA) clearance. Age was a significant predictor for tubular atrophy, fibrosis and sclerosis. Pack‐years of smoking increased the risk of tubular atrophy, fibrosis and arteriolohyalinosis. The alternative scoring of tubular atrophy showed a stronger association with smoking, but a weaker association with age, compared with the original one. Limited histopathological changes are common in healthy kidney donors around 50 years of age with normal kidney function. We propose that a cut‐off of ≤5% yields a better definition of grade 0 tubular atrophy compared with the established cut‐off of >0%.
Negligible structural development and edge influence on the understorey at 16–17‐yr‐old clear‐cut edges in black spruce forest
Authors: Harper Karen A. , Drapeau Pierre , Lesieur Daniel , Bergeron Yves
Published: February 2016

Questions

What is the distance of edge influence on the structure and understorey composition at 16–17‐yr‐old cut edges in black spruce boreal forest? How do these edges compare with more recent 2–5‐yr‐old cut edges in the same region?

Location

Northwestern Quebec, Canada.

Methods

Forest structure and understorey composition were sampled along transects perpendicular to ten 16–17‐yr‐old clear‐cut edges, and compared to published results from 2–5‐yr‐old cut edges. We used randomization tests to assess the magnitude and distance of edge influence, and to compare edge influence between different edge ages.

Results

Black spruce forest next to the 16–17‐yr‐old cut edges was structurally and compositionally very similar to interior forest, with little edge influence from harvesting beyond 5 m into the forest. Edge influence on the understorey was weak (low magnitude) and not very extensive (short distance) at these edges, with no significant edge influence on the abundance of individual species. Logs peaked in abundance on the forest side of the edge, with values higher than in either adjacent ecosystem.

Conclusions

Overall, 16–17‐yr‐old cut edges in black spruce forest showed little evidence of further structural change compared to the 2–5‐yr‐old cut edges. Structural development of these edges as well as regeneration of the disturbed areas also resulted in reduced edge influence on the understorey. Instead, clear‐cut edges in black spruce forest may experience more forest influence on the regenerating disturbed area.
Long‐term late season mowing maintains diversity in southernUStallgrass prairie invaded byBothriochloa ischaemum
Authors: Dee Justin R. , Thomas Shyam M. , Thompson Steven D. , Palmer Michael W.
Published: February 2016

Questions

While mowing is a viable management tool for the maintenance of diversity in grasslands, the suitability of mowing in grasslands with invasion by exotic plants is poorly understood. In this 18‐yr study, we investigate the effects of long‐term mowing on a tallgrass prairie community invaded by exotic yellow bluestem (Bothriochloa ischaemum;BOIS). We explore the influence ofBOISon species richness and composition in the face of different mowing treatments as well as monitoring any post‐treatment legacy effects.

Location

Northeast central Oklahoma,US.

Methods

A total of 144 permanent plots were laid out comprising eight treatments (i.e. all combinations of Mar, Jun and Sept, mows resulting in three single mows, three double mows, one triple mow and an un‐mowed control). Plots were mowed 1996–2011 and recovery was monitored through 2014. Repeated mixed modelANOVA,PERMANOVAand principal response curves were employed to analyse species richness and compositional changes from mowing. Correlation was used to explore the effects ofBOISon species richness.

Results

Mowing resulted in higher species richness relative to the absence of mowing, with the highest levels being sustained in the late season mown plots throughout the study. Once mowing had ceased, early season mown plots declined in species richness down to the same levels as the un‐mown plots, concomitant with the sharpest increased cover ofBOISin these plots relative to all other treatments. Overall, we found a strong negative correlation betweenBOIScover and species richness. Species dissimilarity was highest between any plot that was mowed and the un‐mown controls, as well as between March and September only treatments.

Conclusions

Our study highlights the potential of mowing in maintaining high species richness. However, the positive response to early season mowing of the exotic yellow bluestem and ensuing negative effect on species richness suggests thatBOIScan confound the favourable effects of mowing. We found only minor post‐treatment legacy effects, sinceBOISstrongly re‐established in the absence of mowing in all previously mown plots, especially the early season mown plots. Thus, we recommend sustained late season mowing to help control the spread ofBOISand maintain species‐rich grasslands.
Impact of stocking rate on species diversity and composition of a subtropical grassland in Argentina
Authors: Pizzio Rafael , Herrero‐Jáuregui Cristina , Pizzio Mariano , Oesterheld Martin
Published: February 2016

Questions

What is the effect of a range of controlled stocking rates on plant species richness and diversity?

Location

Subtropical grasslands of Corrientes, Argentina, South America.

Methods

We studied the effect of three controlled stocking rates (0.6, 0.8 and 1.0 cow equivalents·ha−1) on species diversity and composition during 8 yr. We calculated species diversity using the antilog of the Shannon‐Wiener index, and considered its two components, richness and evenness. We also assessed the proportion of prostrate and erect species. Species abundance was based on biomass estimations.

Results

Species diversity under high stocking rates gradually decreased throughout the experiment and became nearly 50% lower than under low stocking rate. This decline was largely accounted for by changes of evenness because species richness was not affected by stocking rates. Species composition clearly diverged among the three treatments over time. Low stocking rate maintained a fairly constant relative cover of erect and prostrate grasses throughout the experiment, whereas intermediate and high stocking rate treatments were gradually and consistently enriched in prostrate grasses and forbs. These effects occurred simultaneously with drastic inter‐annual changes likely driven by annual precipitation.

Conclusions

The range of stocking rates had no effect on species richness, but reduced diversity through the effect on evenness. High stocking rate progressively increased the proportion of prostrate species in the biomass.
Shrub encroachment influences herbaceous communities in flooded grasslands of a neotropical savanna wetland
Authors: Barbosa da Silva Fernando Henrique , Arieira Julia , Parolin Pia , Nunes da Cunha Cátia , Junk Wolfgang Johannes
Published: February 2016

Question

The encroachment of woody species has been globally reported over much of arid and semi‐arid biomes, and has been associated with a decrease in cover and number of herbaceous species. How does the encroachment of a woody shrub affect herbaceous community structure and species composition in grasslands of a wetland ecosystem?

Location

Seasonally flooded grasslands in a Neotropical Hyperseasonal Savanna, the Pantanal wetland, Brazil.

Methods

We investigated the effect of the encroaching plant Combretum laxum on a herbaceous community from seasonally flooded grasslands in the Pantanal wetland using 29 vegetation samples representing encroachment at different spatio‐temporal stages. The point quadrat method was used to acquire vegetation data, as plant cover, species richness (S) and Shannon‐Wiener diversity index (H’). We evaluated the existence of stages of encroachment related to differences in vegetation structure and species composition using non‐metric multidimensional scaling ordination and analysis of similarity. The response of the herbaceous community to shrub advance was analysed using linear and quadratic polynomial regression models. Model fitness was tested using the ACI.

Results

The advance of the woody encroaching plant C. laxum over the seasonally flooded grassland occurs in three stages: grassland stage, shrub islands stage and shrubland stage. The initial advance of C. laxum over the grassland, represented by the shrub islands stage was correlated to an increase in species richness and a decrease in important native forage grasses. Critical changes in the herbaceous community were observed when the encroaching plant covered >30% of the periodically flooded grassland, when the richness of herbaceous species dropped from 22 to four.

Conclusions

Woody encroachment causes impoverishment and simplification of the herbaceous community. The shift from a grass‐ to a shrub‐dominated state is related to the reduction in important grassland‐obligate species, forage resources for herbivore livestock and wild animals, affecting the ecological dynamics and the economy of rangelands. Conservation of these grassland ecosystems depends on rangeland management practices guided by scientific knowledge on the causes and consequences of plant community changes.
Safety, pharmacokinetics and pharmacodynamics of GLPG0974, a potent and selective FFA2 antagonist, in healthy male subjects
Authors: Namour Florence , Galien René , Van Kaem Tim , Van der Aa Annegret , Vanhoutte Frédéric , Beetens Johan , van't Klooster Gerben
Published: February 2016

Aims

Free fatty acids (FFA) can act as direct signalling molecules through activation of several membrane‐bound G‐protein coupled receptors. The FFA2 receptor (known as GPR43) is activated by short chain fatty acids (SCFA) such as acetate and has been shown to play a major role in SCFA‐induced neutrophil activation and migration and to contribute in the development and control of inflammation. GLPG0974 is a potent and selective antagonist of the human FFA2. The main objectives of the two phase 1 trials were to characterize the safety, tolerability, pharmacokinetics and pharmacodynamics of GLPG0974.

Methods

Two consecutive randomized, double‐blind, placebo‐controlled, single centre trials in healthy subjects were performed. In the first, GLPG0974 was administered as single doses up to 250 mg and in the second, multiple daily doses up to 400 mg for 14 days were evaluated. Non‐compartmental analysis was used to determine GLPG0974 pharmacokinetics while target engagement was investigated through the inhibition of neutrophils in acetate‐simulated whole blood samples using surface expression of CD11b activated epitope as a marker of neutrophil activation.

Results

The investigation of safety/tolerability and pharmacokinetics in the early development phase showed that GLPG0974 was safe and well tolerated up to a daily dose of 400 mg. GLPG0974 showed good and dose proportional exposure up to 400 mg daily as well as a substantial and sustained inhibition of acetate‐stimulated neutrophil activation.

Conclusion

Based on these results, a proof‐of‐concept study was initiated to evaluate the safety, tolerability and efficacy of GLPG0974 in patients with mild to moderate ulcerative colitis.
Limited information estimation of the diffusion‐based item response theory model for responses and response times
Authors: Ranger Jochen , Kuhn Jörg‐Tobias , Szardenings Carsten
Published: February 2016

Psychological tests are usually analysed with item response models. Recently, some alternative measurement models have been proposed that were derived from cognitive process models developed in experimental psychology. These models consider the responses but also the response times of the test takers. Two such models are the Q‐diffusion model and the D‐diffusion model. Both models can be calibrated with the diffIRT package of the R statistical environment via marginal maximum likelihood (MML) estimation. In this manuscript, an alternative approach to model calibration is proposed. The approach is based on weighted least squares estimation and parallels the standard estimation approach in structural equation modelling. Estimates are determined by minimizing the discrepancy between the observed and the implied covariance matrix. The estimator is simple to implement, consistent, and asymptotically normally distributed. Least squares estimation also provides a test of model fit by comparing the observed and implied covariance matrix. The estimator and the test of model fit are evaluated in a simulation study. Although parameter recovery is good, the estimator is less efficient than the MML estimator.
Extracellular matrix degradation via enolase/plasminogen interaction: Evidence for a mechanism conserved in Metazoa
Authors: Grossi Gerarda , Grimaldi Annalisa , Cardone Rosa A. , Monné Magnus , Reshkin Stephan J. , Girardello Rossana , Greco Maria R. , Coviello Elena , Laurino Simona , Falabella Patrizia
Published: February 2016

Background Information

While enolase is a ubiquitous metalloenzyme involved in the glycolytic pathway, it is also known as a multifunctional protein, since enolases anchored on the outer surface of the plasma membrane are involved in tissue invasion.

Results

We have identified an extracellular enolase (Ae‐ENO) produced by the teratocytes, embryonic cells of the insect parasitoid Aphidius ervi. We demonstrate that Ae‐ENO, although lacking a signal peptide, accumulates in cytoplasmic vesicles oriented towards the cell membrane. Ae‐ENO binds to and activates a plasminogen‐like molecule inducing digestion of the host tissue and thereby ensuring successful parasitism.

Conclusions

These results support the hypothesis that plasminogen‐like proteins exist in invertebrates. Interestingly the activation of a plasminogen‐like protein is mediated by a mechanisms involving the surface enolase/fibrinolytic system considered, until now, exclusive of vertebrates, and that instead is conserved across species.

Significance

To our knowledge, this is the first example of enolase mediated Plg‐like binding and activation in insect cells, demonstrating the existence of an ECM degradation process via a Plg‐like protein in invertebrates.
Protease‐activated receptor 4: from structure to function and back again
Authors: French Shauna L , Hamilton Justin R
Published: February 2016

Protease‐activated receptors are a family of four GPCRs (PAR1–PAR4) with a number of unique attributes. Nearly two and a half decades after the discovery of the first PAR, an antagonist targeting this receptor has been approved for human use. The first‐in‐class PAR1 antagonist, vorapaxar, was approved for use in the USA in 2014 for the prevention of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. These recent developments indicate the clinical potential of manipulating PAR function. While much work has been aimed at uncovering the function of PAR1 and, to a lesser extent, PAR2, comparatively little is known regarding the pharmacology and physiology of PAR3 and PAR4. Recent studies have begun to develop the pharmacological and genetic tools required to study PAR4 function in detail, and there is now emerging evidence for the function of PAR4 in disease settings. In this review, we detail the discovery, structure, pharmacology, physiological significance and therapeutic potential of PAR4.

Linked Articles

This article is part of a themed section on Molecular Pharmacology of G Protein‐Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc
Synthesis and Biological Evaluation of 1,2,3‐triazole tethered Pyrazoline and Chalcone Derivatives
Authors: Hussaini Syed Mohammed Ali , Yedla Poornachandra , Babu Korrapati Suresh , Shaik Thokhir B. , Chityal Ganesh Kumar , Kamal Ahmed
Published: February 2016

A series of pyrazoline derivatives and corresponding chalcone intermediates with substituents same as combretastatin‐A4(CA‐4) conjugated with triazole nucleus has been synthesized and evaluated for their anticancer potential. Sulphorhodamine B(SRB) assay indicated compound 12c to be the most active compound from the series with GI50 value of 6.7 μm against the human liver carcinoma cell line HepG2. Interestingly, the intermediate 11c exhibited more promising cytotoxicity demonstrating GI50 value of 1.3 μm against the prostate cancer cell line DU145. Compounds 11c and 12c caused accumulation of cells in G2/M phase and inhibited tubulin polymerization. Furthermore, these compounds reduce the mitochondrial membrane potential and activate caspases 3 and 9, thereby indicating their ability to trigger apoptosis.
Understanding Delay in Developmental Disorders
Authors: Thomas Michael S. C.
Published: February 2016

Researchers in developmental disorders frequently refer to abilities that are in line with mental age as simply delayed. The qualifier simply might imply an existing theory of developmental delay that is well understood and uninteresting (perhaps because it is an exaggerated form of individual differences, the responsibility of other researchers). In this article, I argue that the notion of delay can be separated into descriptive and explanatory versions. The descriptive version is often used too coarsely to be helpful. Instead, we need an approach based on developmental trajectories to separate types of descriptive delay, which may then have different underlying causes. The explanatory version is poorly articulated in developmental theory. One useful way to deepen our understanding of delay is by building computational models that simulate development in large populations of individuals and explicitly implementing factors that cause variations in development. Finally, I suggest that dividing research among separate investigators of typical development, individual differences, and developmental disorders may be counterproductive if the underlying mechanisms recognize no such distinction.
When silence is noise: infantile‐onset Barth syndrome caused by a synonymous substitution affecting TAZ gene transcription
Authors: Ferri L. , Dionisi‐Vici C. , Taurisano R. , Vaz F. M. , Guerrini R. , Morrone A.
Published: February 2016

Barth syndrome (BTHS) is an X‐linked inborn error of metabolism which affects males. The main manifestations are cardiomyopathy, myopathy, hypotonia, growth delay, intermittent neutropenia and 3‐methylglutaconic aciduria. Diagnosis is confirmed by mutational analysis of the TAZ gene and biochemical dosage of the monolysocardiolipin/tetralinoleoyl cardiolipin (MLCL:L4‐CL) ratio. We report a 6‐year‐old boy who presented with severe hypoglycemia, lactic acidosis and severe dilated cardiomyopathy soon after birth. The MLCL:L4‐CL ratio confirmed BTHS (3.90 on patient's fibroblast, normal: 0–0.3). Subsequent sequencing of the TAZ gene revealed only the new synonymous variant NM_000116.3 (TAZ):c.348C>T p.(Gly116Gly), which did not appear to affect the protein sequence. In silico prediction analysis suggested the new c.348C>T nucleotide change could alter the TAZ mRNA splicing processing. We analyzed TAZ mRNAs in the patient's fibroblasts and found an abnormal skipping of 24 bases (NM_000116.3:c.346_371), with the consequent ablation of 8 amino acid residues in the tafazzin protein (NP_000107.1:p.Lys117_Gly124del). Molecular analysis of at risk female family members identified the patient's sister and mother as heterozygous carriers. Apparently harmless synonymous variants in the TAZ gene can damage gene expression. Such findings widen our knowledge of molecular heterogeneity in BTHS.
Atp13a2 Deficiency Aggravates Astrocyte‐Mediated Neuroinflammation via NLRP3 Inflammasome Activation
Authors: Qiao Chen , Yin Nuo , Gu Huan‐Yu , Zhu Jia‐Lei , Ding Jian‐Hua , Lu Ming , Hu Gang
Published: February 2016

Aim

Atp13a2 (Park9) gene encodes a transmembrane lysosomal P5‐type ATPase (ATP13A2), and its missense or truncation mutations leads to lysosomal dysfunction and consequently results in neuronal death in the pathogenesis of Parkinson's disease (PD). Nevertheless, the roles of ATP13A2 in the biological features of astrocytes, especially in the regulation of PD‐related neuroinflammation, have not been investigated.

Methods

We cultured primary neurons and astrocytes from mouse midbrain to investigate the mechanisms for astrocyte ATP13A2‐regulated lysosomal function and neuroinflammation following 1‐methyl‐4‐phenylpyridinium (MPP+) treatment.

Results

We found that astrocytes expressed considerable levels of ATP13A2 and deficiency of ATP13A2 in astrocyte‐induced intense inflammation, which exacerbated dopaminergic neuron damage after exposure to MPP+. Notably, lack of ATP13A2 increased lysosomal membrane permeabilization and cathepsin B release, which in turn exacerbated activation of nod‐like receptor protein 3 (NLRP3) inflammasome to produce excess IL‐1β from astrocytes. Furthermore, overexpression of ATP13A2 reversed MPP+‐induced cathepsin B release and NLRP3 inflammasome activation in astrocytes.

Conclusions

Our results have revealed a novel role of ATP13A2 in modulating astrocyte‐mediated neuroinflammation via NLRP3 inflammasome activation, thus bringing to light of a direct link between astrocyte lysosome and neuroinflammation in the pathological model of PD.
Systematic review of evidence and consensus on perianal fistula: an analysis of national and international guidelines
Authors: de Groof E. J. , Cabral V. N. , Buskens C. J. , Morton D. G. , Hahnloser D. , Bemelman W. A. ,   the research committee of the European Society of Coloproctology
Published: February 2016

Aim

Treatment of perianal fistula has evolved with the introduction of new techniques and biologicals in Crohn's disease (CD). Several guidelines are available worldwide, but many recommendations are controversial or lack high‐quality evidence. The aim of this work was to provide an overview of the current available national and international guidelines for perianal fistula and to analyse areas of consensus and areas of conflicting recommendations, thereby identifying topics and questions for future research.

Method

MEDLINE, EMBASE and PubMed were systematically searched for guidelines on perianal fistula. Inclusion was limited to papers in English less than 10 years old. The included topics were classified as having consensus (unanimous recommendations in at least two‐thirds of the guidelines) or controversy (fewer than three guidelines commenting on the topic or no consensus) between guidelines. The highest level of evidence was scored as sufficient (level 3a or higher of the Oxford Centre for Evidence‐based Medicine Levels of Evidence 2009, http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/) or insufficient.

Results

Twelve guidelines were included and topics with recommendations were compared. Overall, consensus was present in 15 topics, whereas six topics were rated as controversial. Evidence levels varied from strong to lack of evidence.

Conclusion

Evidence on the diagnosis and treatment of perianal fistulae (cryptoglandular or related to CD) ranged from nonexistent to strong, regardless of consensus. The most relevant research questions were identified and proposed as topics for future research.
A case of brucellosis presenting with pericardial and pleural effusion
Authors: Altas Meryem Hilal , Karli Arzu , Sensoy Gulnar , Koken Ozlem , Yurek Burak , Baysal Kemal
Published: February 2016

Brucellosis is a worldwide zoonotic infection with a diverse clinical presentation. Pericardial and pleural involvement is rare in brucellosis. There is no presentation with pleural and pericardial effusion in childhood brusellosis. In endemic countries Brucellosis must thought as an unknown etiology of pericardial and pleural effusion.
Eurotransplant donor‐risk‐index and recipient factors: influence on long‐term outcome after liver transplantation – A large single‐center experience
Authors: Schoening Wenzel , Helbig Michael , Buescher Niklas , Andreou Andreas , Schmitz Volker , Bahra Marcus , Puhl Gero , Pascher Andreas , Pratschke Johann , Seehofer Daniel
Published: February 2016

The organ shortage has led to increased use of marginal organs. The Eurotransplant Donor‐Risk‐Index (ET‐DRI) was established to estimate outcome after Liver Transplantation (LT). Currently, data on impact of ET‐DRI on long‐term outcome for different indications and recipient conditions are missing. Retrospective, single‐center analysis of long‐term graft survival (GS) of 1767 adult primary LTs according to indication, labMELDcategory (1: ≤18; 2: >18–25; 3: >25–35; 4: >35), and ET‐DRI. Mean ET‐DRI in our cohort was 1.63 (±0.43). One‐, 10, and 15‐yr GS was 83.5%, 63.3%, and 54.8%. Long‐term GS was significantly influenced by ET‐DRI. Accordingly, four ET‐DRI categories were defined and analyzed with respect to underlying disease. Significant impact of these categories was observed for: Alcohol, cholestatic/autoimmune diseases (CD/AIH), and HCV, but not for HCC, HBV, cryptogenic cirrhosis, and acute liver failure. labMELD categories showed no significant influence on graft, but on patient survival. Matching ET‐DRI categories with labMELD revealed significant differences in long‐term GS for labMELDcategories 1, 2, and 3, but not 4. In multivariate analysis, HCV combined with ET‐DRI > 2 and labMELDcategory 3 combined with ET‐DRI > 2 emerged as negative predictors. To achieve excellent long‐term graft survival, higher risk organs (ET‐DRI > 1.4) should be used restrictively for patients with CD/AIH or HCV. Organs with ET‐DRI > 2 should be avoided in patients with a labMELD of >25–35.
Low incidence of anti‐drug antibodies in patients with type 2 diabetes treated with once‐weekly glucagon‐like peptide‐1 receptor agonist dulaglutide
Authors: Milicevic Z. , Anglin G. , Harper K. , Konrad R. J. , Skrivanek Z. , Glaesner W. , Karanikas C. A. , Mace K.
Published: February 2016

Therapeutic administration of peptides may result in anti‐drug antibody (ADA) formation, hypersensitivity adverse events (AEs) and reduced efficacy. As a large peptide, the immunogenicity of once‐weekly glucagon‐like peptide‐1 (GLP‐1) receptor agonist dulaglutide is of considerable interest. The present study assessed the incidence of treatment‐emergent dulaglutide ADAs, hypersensitivity AEs, injection site reactions (ISRs), and glycaemic control in ADA‐positive patients in nine phase II and phase III trials (dulaglutide, N = 4006; exenatide, N = 276; non‐GLP‐1 comparators, N = 1141). Treatment‐emergent dulaglutide ADAs were detected using a solid‐phase extraction acid dissociation binding assay. Neutralizing ADAs were detected using a cell‐based assay derived from human endothelial kidney cells (HEK293). A total of 64 dulaglutide‐treated patients (1.6% of the population) tested ADA‐positive versus eight (0.7%) from the non‐GLP‐1 comparator group. Of these 64 patients, 34 (0.9%) had dulaglutide‐neutralizing ADAs, 36 (0.9%) had native‐sequence GLP‐1 (nsGLP‐1) cross‐reactive ADAs and four (0.1%) had nsGLP‐1 neutralization ADAs. The incidence of hypersensitivity AEs and ISRs was similar in the dulaglutide versus placebo groups. No dulaglutide ADA‐positive patient reported hypersensitivity AEs. Because of the low incidence of ADAs, it was not possible to establish their effect on glycaemic control.
Sustained efficacy of insulin pump therapy compared with multiple daily injections in type 2 diabetes: 12‐month data from the OpT2mise randomized trial
Authors: Aronson R. , Reznik Y. , Conget I. , Castañeda J. A. , Runzis S. , Lee S. W. , Cohen O. ,   for the OpT2mise Study Group
Published: February 2016

Aims

To compare insulin pump therapy and multiple daily injections (MDI) in patients with type 2 diabetes receiving basal and prandial insulin analogues.

Methods

After a 2‐month dose‐optimization period, 331 patients with glycated haemoglobin (HbA1c) levels ≥8.0% and ≤12% were randomized to pump therapy or continued MDI for 6 months [randomization phase (RP)]. The MDI group was subsequently switched to pump therapy during a 6‐month continuation phase (CP). The primary endpoint was the between‐group difference in change in mean HbA1c from baseline to the end of the RP.

Results

The mean HbA1c at baseline was 9% in both groups. At the end of the RP, the reduction in HbA1c was significantly greater with pump therapy than with MDI (−1.1 ± 1.2% vs −0.4 ± 1.1%; p < 0.001). The pump therapy group maintained this improvement to 12 months while the MDI group, which was switched to pump therapy, showed a 0.8% reduction: the final HbA1c level was identical in both arms. In the RP, total daily insulin dose (TDD) was 20.4% lower with pump therapy than with MDI and remained stable in the CP. The MDI–pump group showed a 19% decline in TDD, such that by 12 months TDD was equivalent in both groups. There were no differences in weight gain or ketoacidosis between groups. In the CP, one patient in each group experienced severe hypoglycaemia.

Conclusions

Pump therapy has a sustained durable effect on glycaemic control in uncontrolled type 2 diabetes.
Rapid selection and characterization of Cry1F resistance in a Brazilian strain of fall armyworm
Authors: Leite Natália A. , Mendes Simone M. , Santos‐Amaya Oscar F. , Santos Chritiane A. , Teixeira Thaís P. M. , Guedes Raul N. C. , Pereira Eliseu J. G.
Published: February 2016

Transgenic maize (Zea mays L., Poaceae) event TC1507, producing the Cry1F protein of Bacillus thuringiensis Berliner, has been used for management of the fall armyworm, Spodoptera frugiperda (JE Smith) (Lepidoptera: Noctuidae), in Brazil since 2009. A strain of S. frugiperda, obtained from field collections of larvae in TC1507 maize in Minas Gerais state in 2010, was selected in the laboratory for resistance to Cry1F using leaves of TC1507 maize in two selection regimes. Continuous exposure of larvae to Cry1F was more effective than exposure for 6, 8, and 10 days in the selection of resistant S. frugiperda individuals. With only four generations of laboratory selection, a strain with high levels of resistance to Cry1F was obtained, as indicated by the survival of insects reared on leaves of TC1507 maize plants and by the more than 300‐fold resistance level measured in bioassays with the purified Cry1F protein. Importantly, reciprocal crosses between control and the Cry1F‐selected strains revealed that the resistance is autosomal and incompletely recessive, and the response obtained in the backcross of the F1 generation with the resistant strain was consistent with simple monogenic inheritance. Additionally, there were no apparent fitness costs associated with resistance either for survival or larval growth on non‐Bt maize leaves. Our findings provide experimental evidence for rapid evolution of Cry1F resistance in S. frugiperda in the laboratory and further reinforce the potential of this species to evolve field resistance to the TC1507 maize as previously reported. The resistant strain isolated in this study provides an opportunity to estimate the resistance allele frequency in the field and to determine the biochemical and molecular basis of the resistance, which should provide further information to assist in the resistance management of S. frugiperda on transgenic maize producing B. thuringiensis proteins.
Forest edges enhance mate‐finding in the invasive European gypsy moth, Lymantria dispar
Authors: Thompson Lily M. , Grayson Kristine L. , Johnson Derek M.
Published: February 2016

Habitat type, fragmentation, and edge effects can play important roles in the mate‐finding abilities of many species. These effects can be particularly pronounced in low‐density populations, which are often found at the margins of species' ranges or at the leading edge of an invasion. The European gypsy moth, Lymantria dispar (L.) (Lepidoptera: Erebidae), is a non‐native insect defoliator in the USA and Canada, where flightless females attract male moths through pheromone production and local extirpation of low‐density populations can be due to mate‐finding failure. To assess the effects of habitat edges on the ability of gypsy moths to find mates, we conducted a release experiment with male gypsy moths using female‐baited trap arrays in fields, at forest edges, and in the forest interior. Reduced mate‐finding was expected in fields and near forest edges based on geographic variation in invasion rates, male flight behavior, and pheromone plume dynamics. However, we found that mate‐finding was highest at forest edges, reduced in fields, and lowest within the forest interior. Within an array, traps closest to the forest edge also had the highest mate‐finding, suggesting that habitat characteristics can influence male flight direction in addition to pheromone cues. These results suggest that a moderate level of forest fragmentation enhances mate‐finding ability in the gypsy moth. Understanding the relationship between habitat heterogeneity and mate‐finding success in invasive species can inform predictions of future spread and assist with management plans that target mating disruption.
Role of chaperone‐mediated autophagy in metabolism
Authors: Tasset Inmaculada , Cuervo Ana Maria
Published: February 2016

Different types of autophagy coexist in most mammalian cells, and each of them fulfills very specific tasks in intracellular degradation. Some of these autophagic pathways contribute to cellular metabolism by directly hydrolyzing intracellular lipid stores and glycogen. Chaperone‐mediated autophagy (CMA), in contrast, is a selective form of autophagy that can only target proteins for lysosomal degradation. Consequently, it was expected that the only possible contribution of this pathway to cellular metabolism would be by providing free amino acids resulting from protein breakdown. However, recent studies have demonstrated that disturbance in CMA leads to important alterations in glucose and lipid metabolism and in overall organism energetics. Here, we describe the unique mechanisms by which CMA contributes to the regulation of cellular metabolism and discuss the possible implications of these previously unknown functions of CMA for the pathogenesis of common metabolic diseases.
Filling a blank on the map: 60 years of fisheries in Equatorial Guinea
Authors: Belhabib D. , Hellebrandt Da Silva D. , Allison E. H. , Zeller D. , Pauly D.
Published: February 2016

Despite a scarcity of pertinent information, it has been possible to reconstruct time series of marine fisheries catches for Equatorial Guinea from 1950 to 2010 using per capita fish consumption and population numbers for small‐scale fisheries, catch rates and number of vessels for industrial fisheries and discard rates to estimate the discarded bycatch. Small‐scale fisheries, industrial large‐scale fisheries, domestic and legal and illegal foreign fisheries and their discards are all included. Total catches were estimated at 2.7 million tonnes over the time period considered, of which 653 000 t were caught domestically compared to 187 000 t reported byFAO. This shows that fisheries have more importance for Equatorial Guinea's food security than the official data suggest. In contrast to what is suggested by official figures, fisheries were shown to be strongly impacted by civil and political unrest; notably, they declined overall because of civil and political conflicts, socio‐demographic dynamics, and a growing role of the newly discovered oil resources, which directly and indirectly threaten the food security of the people of Equatorial Guinea.
From global to regional and back again: common climate stressors of marine ecosystems relevant for adaptation across five ocean warming hotspots
Authors: Popova Ekaterina , Yool Andrew , Byfield Valborg , Cochrane Kevern , Coward Andrew C. , Salim Shyam S. , Gasalla Maria A. , Henson Stephanie A. , Hobday Alistair J. , Pecl Gretta T. , Sauer Warwick H. , Roberts Michael J.
Published: February 2016

Ocean warming ‘hotspots’ are regions characterized by above‐average temperature increases over recent years, for which there are significant consequences for both living marine resources and the societies that depend on them. As such, they represent early warning systems for understanding the impacts of marine climate change, and test‐beds for developing adaptation options for coping with those impacts. Here, we examine five hotspots off the coasts of eastern Australia, South Africa, Madagascar, India and Brazil. These particular hotspots have underpinned a large international partnership that is working towards improving community adaptation by characterizing, assessing and projecting the likely future of coastal‐marine food resources through the provision and sharing of knowledge. To inform this effort, we employ a high‐resolution global ocean model forced by Representative Concentration Pathway 8.5 and simulated to year 2099. In addition to the sea surface temperature, we analyse projected stratification, nutrient supply, primary production, anthropogenic CO2‐driven ocean acidification, deoxygenation and ocean circulation. Our simulation finds that the temperature‐defined hotspots studied here will continue to experience warming but, with the exception of eastern Australia, may not remain the fastest warming ocean areas over the next century as the strongest warming is projected to occur in the subpolar and polar areas of the Northern Hemisphere. Additionally, we find that recent rapid change in SST is not necessarily an indicator that these areas are also hotspots of the other climatic stressors examined. However, a consistent facet of the hotspots studied here is that they are all strongly influenced by ocean circulation, which has already shown changes in the recent past and is projected to undergo further strong change into the future. In addition to the fast warming, change in local ocean circulation represents a distinct feature of present and future climate change impacting marine ecosystems in these areas.