bluuebunny/crossref_metadata_2025 huggingface dataset:
Does somatosensation change with age in children and adolescents? A systematic review
Authors: Taylor S. , McLean B. , Falkmer T. , Carey L. , Girdler S. , Elliott C. , Blair E.
Published: October 2016

Background

Somatosensory modalities, such as touch, proprioception and haptic ability, greatly influence the achievement of developmental milestones for children. Describing somatosensory impairment, natural variability and typical or expected developmental changes across age groups will help establish frameworks for intervention in clinical populations. This systematic review aimed to determine how different somatosensory modalities develop across childhood into adolescence to use as a point of reference for children at risk of somatosensory impairment.

Methods

Searches of five electronic databases were undertaken through EBSCO‐host (MEDLINE, CINAHL, PsycINFO, SPORTDiscus and ERIC) for studies measuring at least one somatosensory modality in typically developing individuals between birth and 18 years and analysed by age. Characteristics of studies were collected including country of origin, sample size, demographics and outcome measure used. Quality assessment and data extraction were performed by two independent reviewers.

Results

Twenty three cross‐sectional studies were included from a total of 188 articles retrieved: 8 examined aspects of touch, 5 proprioception and 10 haptic ability. Variability of study designs and variation in assessment tools precluded any formal meta‐analysis.

Conclusions

Somatosensation matures through childhood into adolescence; however, the present review found the pattern of somatosensory development varied depending on the assessment tool used and the aspect of somatosensation being measured, making it difficult to describe typical performance. There is a need for comprehensive assessment batteries to measure the somatosensation, including touch, proprioception and haptic ability, of children at risk of somatosensory impairment to aid in the development of effective interventions.
Course of serum autoantibodies in patients after acute angle‐closure glaucoma attack
Authors: Lorenz Katrin , Beck Sabine , Keilani Munir M , Wasielica‐Poslednik Joanna , Pfeiffer Norbert , Grus Franz H
Published: October 2016

Background

The aim of our investigation was to analyze the autoantibody ‐reactivities of patients after acute angle‐closure glaucoma (AACG) by means of a protein microarray approach to identify intraocular pressure(IOP)‐dependent antibodies.

Methods

Collected sera from different study time points (AACG n = 6, 0, 2, 4 and 12 weeks) and control group (CTRL n = 11, 0 and 12 weeks) were analyzed. Protein‐microarrays were incubated with sera, and occurring immunoreactivities were visualized with fluorescence labeled secondary antibodies. To detect changes, spot intensities were digitized and compared with statistical techniques.

Results

Three autoantibodies with significant level‐alteration in the time course of the survey could be identified. Immunoreactivities to heat shock 27‐kDa protein (HSP27), tubulin–tyrosine ligase‐like protein 12 (TTLL12), and neuron‐specific enolase (NSE) show an increasing linear trend from week 0 up to week 12 with a positive correlation coefficient (P ≤ 0.05, r ≥ 0.4). In the CTRL‐ group, no significant alterations could be detected in corresponding autoantibody‐level. Analysis of variance revealed significant changes of antibody‐level between certain time points (anti‐HSP27 antibody [week 0 vs. 2], anti‐TTLL12 antibody [week 0 vs. 12], and anti‐NSE antibody [week 4 vs. 12] [P ≤ 0.05, respectively]) in AACG group.

Conclusions

With this autoantibodies profiling approach, we were able to detect autoimmune reactivities in sera of patients without former indication for glaucomatous damage after rise of IOP due to AACG attack. After further validation in subsequent studies, this autoantibodies could give further insights into the pathogenesis of glaucoma and could possibly help to understand the effect of IOP on glaucomatous optic neuropathy.
The NobelGuide® All‐on‐4® Treatment Concept for Rehabilitation of Edentulous Jaws: A Retrospective Report on the 7‐Years Clinical and 5‐Years Radiographic Outcomes
Authors: Lopes Armando , Maló Paulo , de Araújo Nobre Miguel , Sánchez‐Fernández Elena , Gravito Inês
Published: October 2016

Background

There is a necessity of studies documenting the long‐term outcome of full‐arch flapless rehabilitations.

Purpose

To evaluate the 7 years implant and prosthesis survival rate and 5‐years marginal bone loss of full‐arch fixed prosthetic rehabilitations supported by implants in immediate function with the All‐on‐4® treatment concept using a computer guided surgical protocol (NobelGuide®, Nobel Biocare).

Materials and Methods

This retrospective clinical study included 111 edentulous patients (n = 53 bruxers; n = 21 smokers; n = 59 systemically compromised), rehabilitated between February 2005 and November 2010 with 532 implants with the All‐on‐4® treatment concept using NobelGuide®. Outcome measures were implant and prosthesis survival, marginal bone loss at 5‐years and the incidence of mechanical and biological complications. Survival was calculated using life‐table analysis. Inferential analysis was performed to compare the difference in marginal bone loss between axial and tilted implants.

Results

Sixteen patients were lost to follow‐up. The implant cumulative survival rate was 94.5% at 7 years. Prosthetic survival was 97.8% (n = 3 prosthetic failures). The average (standard deviation) marginal bone loss at 5 years was 1.3 mm (1.06 mm) overall, 1.27 mm (1.02 mm) for tilted implants and 1.34 mm (1.1 mm) for axial implants (p < .001). Ninety‐one patients experienced complications in the provisional prostheses (n = 47 patients who were bruxers; n = 25 patients with implant‐supported rehabilitation as opposing dentition) ranging from prosthetic fracture (n = 66 patients) to abutment or prosthetic screw loosening (n = 74 patients). Thirty‐three patients experienced complications in the definitive prostheses (all exclusive to patients who were bruxers or had implant‐supported rehabilitations as opposing dentition) ranging from acrylic‐resin prosthetic/crown fracture (n = 23 patients) to abutment or prosthetic screw loosening (n = 10 patients). Twenty‐five patients (22%) registered peri‐implant pathology.

Conclusions

Within the limitations of this study, it is possible to conclude that this treatment modality for completely edentulous jaws is possible with high long‐term survival outcomes. Bruxing and smoking habits had a negative impact on implant failure, mechanical, and biological complications.
Molecular phylogeny of the fern family Blechnaceae (Polypodiales) with a revised genus‐level treatment
Authors: de Gasper André L. , Almeida Thaís E. , Dittrich Vinícius A. de O. , Smith Alan R. , Salino Alexandre
Published: October 2016

Blechnaceae, a leptosporangiate fern family nested within eupolypods II, comprises 200–250 species, typically divided among seven to nine genera. Despite recent molecular studies of the family, it still lacks a modern taxonomic update based on broad sampling from the two centres of diversity—the Neotropics and Australasia/Oceania. To test generic circumscriptions, we have assembled the broadest dataset thus far, from three plastid regions (rbcL, rps4‐trnS, trnL‐trnF) and with taxonomic sampling focused on both major diversity centres. Our sampling includes 156 taxa and 178 newly generated sequences. We recognize three subfamilies, each corresponding to a highly supported clade across all analyses (maximum parsimony, Bayesian inference and maximum likelihood). The genera Salpichlaena, Stenochlaena and Telmatoblechnum are monophyletic, while Blechnum is polyphyletic, because Brainea, Doodia and Sadleria all nest within it. We outline and explain a plan to resolve the polyphyly of Blechnum by recognizing additional, monophyletic, segregate genera.
Generation of a transgenic medaka (Oryzias latipes) strain for visualization of nuclear dynamics in early developmental stages
Authors: Inoue Takanobu , Iida Atsuo , Maegawa Shingo , Sehara‐Fujisawa Atsuko , Kinoshita Masato
Published: October 2016

In this study, we verified nuclear transport activity of an artificial nuclear localization signal (aNLS) in medaka fish (Oryzias latipes). We generated a transgenic medaka strain expresses the aNLS tagged enhanced green fluorescent protein (EGFP) driven by a medaka beta‐actin promoter. The aNLS‐EGFP was accumulated in the nuclei of somatic tissues and yolk nuclei of oocytes, but undetectable in the spermatozoa. The fluorescent signal was observed from immediately after fertilization by a maternal contribution. Furthermore, male and female pronuclei were visualized in fertilized eggs, and nuclear dynamics of pronuclear fusion and subsequent cleavage were captured by time‐lapse imaging. In contrast, SV40NLS exhibited no activity of nuclear transport in early embryos. In conclusion, the aNLS possesses a strong nuclear localization activity and is a useful probe for fluorescent observation of the pronuclei and nuclei in early developmental stage of medaka.
The Normative Distinctiveness of the European Union in International Development: Stepping Out of the Shadow of the World Bank?
Authors: Orbie Jan , Delputte Sarah , Bossuyt Fabienne , Debusscher Petra , Biondo Karen Del , Reynaert Vicky , Verschaeve Joren
Published: October 2016

Although the EU has shown a strong ambition to put a distinctive stamp on the international aid agenda over the past 15 years, it has also been pointed out that its policies suffer from a series of collective action problems. This article explores how both relate to one another. This article examines the EU's normative distinctiveness in contrast to the World Bank, focusing on policy norms in the field of governance, aid effectiveness and social development. We argue that collective action problems do not necessarily hamper EU distinctiveness: they are also a symptom of a strong EU desire to pressure European actors to come up with norms that pacify disagreements.
A positive correlation exists between neurotrauma and TGF‐β1‐containing microglia in rats
Authors: Chio Chung‐Ching , Lin Mao‐Tsun , Chang Ching‐Ping , Lin Hung‐Jung
Published: October 2016

Background

Transforming growth factor‐beta 1 (TGF‐β1) regulates many processes after traumatic brain injury (TBI). Both Neuro AiD™ (MLC601) and astragaloside (AST) attenuate microglia activation in rats with TBI. The purpose of this study was to investigate whether MLC601 or AST improves output of TBI by affecting microglial expression of TGF‐β1.

Materials and methods

Adult male Sprague‐Dawley rats (120 in number) were used to investigate the contribution of TGF‐β1‐containing microglia in the MLC601‐mediated or the AST‐mediated neuroprotection in the brain trauma condition using lateral fluid percussion injury.

Results

Pearson correlation analysis revealed that there was a positive correlation between brain injury (evidenced by both brain contused volume and neurological severity score) and the cortical numbers of TGF‐β1‐containing microglia for the rats (n = 12) 4 days post‐TBI. MLC601 or AST significantly (P < 0·05) attenuated TBI‐induced brain contused volume (119 ± 14 mm3 or 108 ± 11 mm3 vs. 160 ± 21 mm3), neurological severity score (7·8 ± 0·3 or 8·1 ± 0·4 vs. 10·2 ± 0·5) and numbers of TGF‐β1‐containing microglia (6% ± 2% or 11% ± 3% vs. 79% ± 7%) for the rats 4 days post‐TBI.

Conclusions

There was a positive correlation between TBI and cortical numbers of TGF‐β1‐containing microglia which could be significantly attenuated by astragaloside or NeuroAiD™ (MLC601) in rats.
Hydrogen peroxide‐mediated conversion of coproheme to heme b by HemQ—lessons from the first crystal structure and kinetic studies
Authors: Hofbauer Stefan , Mlynek Georg , Milazzo Lisa , Pühringer Dominic , Maresch Daniel , Schaffner Irene , Furtmüller Paul G. , Smulevich Giulietta , Djinović‐Carugo Kristina , Obinger Christian
Published: October 2016

Heme biosynthesis in Gram‐positive bacteria follows a recently described coproporphyrin‐dependent pathway with HemQ catalyzing the decarboxylation of coproheme to heme b. Here we present the first crystal structure of a HemQ (homopentameric coproheme‐HemQ from Listeria monocytogenes) at 1.69 Å resolution and the conversion of coproheme to heme b followed by UV‐vis and resonance Raman spectroscopy as well as mass spectrometry. The ferric five‐coordinated coproheme iron of HemQ is weakly bound by a neutral proximal histidine H174. In the crystal structure of the resting state, the distal Q187 (conserved in Firmicutes HemQ) is H‐bonded with propionate p2 and the hydrophobic distal cavity lacks solvent water molecules. Two H2O2 molecules are shown to be necessary for decarboxylation of the propionates p2 and p4, thereby forming the corresponding vinyl groups of heme b. The overall reaction is relatively slow (kcat/KM = 1.8 × 102 m−1·s−1 at pH 7.0) and occurs in a stepwise manner with a three‐propionate intermediate. We present the noncovalent interactions between coproheme and the protein and propose a two‐step reaction mechanism. Furthermore, the structure of coproheme‐HemQ is compared to that of the phylogenetically related heme b‐containing chlorite dismutases.

Database

Structural data are available in the PDB under the accession number 5LOQ.
Physical and functional interactions between nucleosomes and Rad27, a critical component of DNA processing during DNA metabolism
Authors: Kwon Buki , Munashingha Palinda Ruvan , Shin Yong‐Keol , Lee Chul‐Hwan , Li Bing , Seo Yeon‐Soo
Published: October 2016

Highly conserved eukaryotic histones are polybasic proteins that package DNA into nucleosomes, a building block of chromatin, allowing extremely long DNA molecules to form compact and discrete chromosomes. The histone N‐terminal tails that extend from the nucleosome core act as docking sites for many proteins through diverse post‐translational modifications, regulating various DNA transactions. In this report, we present evidence that the nucleosomes can positively regulate the enzymatic activity of Rad27 (yeast Fen1), a major processing enzyme important for Okazaki fragment in eukaryotes. We found that individual histones, histone octamers, and nucleosomes are able to stimulate Rad27 in a manner dependent on the N‐terminal tails of histones. Kinetic analyses suggest that an increase in catalytic efficiency of Rad27 was mainly due to increased affinity between DNA substrates and Rad27. It appears that the physical interaction in vivo between histones and Rad27 results in the enrichment of Rad27 in the vicinity of chromatin, increasing the availability of Rad27 for various DNA metabolisms. These results indicate that nucleosomes are not a mere structural component of chromatin, but an active regulator of DNA metabolisms that serves to ensure the efficient and faithful processing of structural intermediates arising during DNA transactions.
Production and Certification of the Reference Material GSB 04‐3258‐2015 as a 143Nd/144Nd Isotope Ratio Reference
Authors: Li Jin , Tang Suo‐han , Zhu Xiang‐kun , Pan Chen‐xu
Published: October 2016

A new certified reference material, labelled GSB 04‐3258‐2015, for use as a 143Nd/144Nd isotope ratio reference has been prepared by the Institute of Geology, Chinese Academy of Geological Sciences, Beijing. Standardization Administration of the People's Republic of China provided the certification for this reference material. This report presents the reference 143Nd/144Nd isotope ratio and supporting production and certification procedures. The reference value was determined by an interlaboratory comparison of results from eleven participating laboratories using MC‐TIMS or MC‐ICP‐MS. The calibration of mass fractionation was conducted by using the exponential law, and the 143Nd/144Nd isotope ratios were normalised to the 146Nd/144Nd isotope ratio value of 0.7219. Isobaric interference of 144Sm on 144Nd was corrected using an interference‐free 147Sm/149Sm isotope ratio value for mass fractionation. GSB 04‐3258‐2015 shows sufficient homogeneity and stability for use as an international isotopic reference material. The certified value was calculated from the unweighted means of the results submitted by the participating laboratories. The 143Nd/144Nd isotope ratio value for GSB 04‐3258‐2015 is 0.512438, with a combined expanded uncertainty (k = 2) of 5 × 10−6. Reference material GSB 04‐3258‐2015 is available upon request from the Institute of Geology, Chinese Academy of Geological Sciences, and may be used for accurate interlaboratory calibration of Nd isotope analysis.
Phylogenetic relationships, song and distribution of the endangered Rufous‐headed Robin Larvivora ruficeps
Authors: Zhao Min , Alström Per , Hu Ruocheng , Zhao Chao , Hao Yan , Lei Fumin , Qu Yanhua
Published: October 2016

The Rufous‐headed Robin Larvivora ruficeps is one of the world's rarest and least known birds. We summarize the known records since it was first described in 1905 from Shaanxi Province, central China. All subsequent Chinese records are from seven adjacent localities in nearby Sichuan Province. We studied its phylogenetic position for the first time using mitochondrial and nuclear markers for all species of Larvivora and a broad selection of other species in the family Muscicapidae. Our results confirmed that L. ruficeps is appropriately placed in the genus Larvivora, and suggested that it is sister to the Rufous‐tailed Robin Larvivora sibilans, with these two forming a sister clade to a clade comprising both the Japanese Robin Larvivora akahige and Ryukyu Robin Larvivora komadori. Siberian Blue Robin Larvivora cyane and Indian Blue Robin Larvivora brunnea form the sister clade to the other Larvivora species. In contrast, song analyses indicated that the song of L. ruficeps is most similar to that of L. komadori, whereas the song of L. sibilans is relatively more similar to that of L. akahige, and songs of L. cyane and L. brunnea closely resemble each other. We used ecological niche modelling to estimate the suitable habitats of L. ruficeps based on the records from breeding grounds, suggesting that north and central Sichuan, south Gansu, south Shaanxi and south‐east Tibet are likely to contain the most suitable habitats for this species.
Skin property can predict the development of skin tears among elderly patients: a prospective cohort study
Authors: Koyano Yuiko , Nakagami Gojiro , Iizaka Shinji , Sugama Junko , Sanada Hiromi
Published: October 2016

The aim of this study was to identify skin properties that may be used to predict the development of a skin tear (ST) among elderly patients. A prospective cohort study was conducted among elderly patients aged 65 and older (N = 149) at a long‐term medical facility in Japan over an 8‐month period. Skin properties at baseline were measured on the forearm using a 20‐MHz ultrasound scanner, which measured the thickness of the dermis layer and low‐echogenic pixels, and skin blotting method, which evaluated the levels of collagen type IV, matrix metalloproteinase‐2 and tumour necrosis factor‐alpha. Adjusted hazard ratios (HRs) for the main confounders were obtained using the Cox proportional hazard model. A total of 52 STs were recorded among the 21 patients, resulting in an incidence rate of 1·13/1000 person‐days. The predictor of STs was dermis thickness (HR = 0·52; 95% confidence interval = 0·33–0·81; P‐value = 0·004). The cut‐off point for dermis thickness was 0·80 mm (area under the curve = 0·77; 95% confidence interval = 0·66–0·88; P‐value = 0·006). Our results suggest that measuring the dermis thickness at baseline is an easy and accurate way to identify a high‐risk patient.
Selective Angiography Using the Radiofrequency Catheter: An Alternative Technique for Mapping and Ablation in the Aortic Cusps
Authors: ROCA‐LUQUE IVO , RIVAS NURIA , FRANCISCO JAUME , PEREZ JORDI , ACOSTA GABRIEL , ORISTRELL GERARD , TERRICABRES MARIA , GARCIA‐DORADO DAVID , MOYA ANGEL
Published: October 2016

Angiography Through the Ablation Catheter in Aortic Cusps

Background

Ablation in aortic cusps could be necessary in up to 15% of the patients, especially in para‐Hisian atrial tachycardia and ventricular arrhythmias arising from outflow tracts. Risk of coronary damage has led to recommendation of systematic coronary angiography (CA) during the procedure. Other image tests as intravascular (ICE) or transesophageal echocardiography (TEE) have been proposed. Both methods have limitations: additional vascular access for ICE and need for additional CA in some patients in case of TEE. We describe an alternative method to assess relation of catheter tip and coronary ostia during ablation in aortic cusps without additional vascular accesses by performing selective angiography with the ablation catheter.

Methods and Results

We prospectively evaluated 12 consecutive patients (69.3 ± 8.5, 6 female) who underwent ablation in right (1), left (5), and noncoronary cusps (6). We performed angiography through the ablation cooled tip radiofrequency catheter at the ablation site. Ablation was effective in 91.6% of the patients (3 patients needed additional ablation out of coronary cusps: pulmonary cusp, right ventricular outflow tract (RVOT), and coronary sinus and 1 patient underwent a second procedure because recurrence). No complications occurred neither during procedure nor follow‐up (6.2 ± 3.8 months). No technical problems occurred with the ablation catheter after contrast injection.

Conclusion

Selective angiography through a cooled‐tip radiofrequency ablation catheter is feasible to assess relation of coronary ostia and ablation site when ablation in aortic cusps. It allows continuous real‐time assessment of this relation, avoids the need for additional vascular accesses and no complications occurred in our series.
Linagliptin improves endothelial function in patients with type 2 diabetes: A randomized study of linagliptin effectiveness on endothelial function
Authors: Shigiyama Fumika , Kumashiro Naoki , Miyagi Masahiko , Iga Ryo , Kobayashi Yuka , Kanda Eiichiro , Uchino Hiroshi , Hirose Takahisa
Published: October 2016

Aims/Introduction

The present multicenter, prospective, controlled, open and randomized three‐arm parallel study was designed to compare the effects of linagliptin with those of metformin on endothelial function.

Materials and Methods

Type 2 diabetes patients treated with 750 mg of metformin (hemoglobin A1c ≥6.0% and <8.0%, n = 96) were randomized to continue metformin 750 mg/day (control group, n = 29), metformin at 1,500 mg/day (metformin group, n = 26) and metformin 750 mg/day supplemented with linagliptin 5 mg/day (linagliptin add‐on group, n = 29) and treated for 16 weeks. Vascular endothelial function was evaluated by flow‐mediated dilation. The primary end‐point was changes in flow‐mediated dilation at 16 weeks relative to baseline.

Results

Linagliptin significantly improved flow‐mediated dilation from baseline (4.9 ± 2.7%) to 16 weeks (6.3 ± 2.7%, P < 0.05), whereas the other groups did not show any changes. Hemoglobin A1c at 16 weeks was significantly lower in the metformin and linagliptin add‐on groups compared with the control (6.6 ± 0.6%, 6.5 ± 0.5% and 7.0 ± 0.6%, respectively). Single and multiple regression analyses showed that apolipoprotein B correlated significantly with change in flow‐mediated dilation, and apolipoprotein B was decreased only in the linagliptin add‐on group (–6.0 ± 11.3 mg/dL, P < 0.01).

Conclusions

Linagliptin for 16 weeks improved endothelial function with a modest improvement in glycemic control. This effect was mediated, at least in part, by reduction in apolipoprotein B. Linagliptin has a protective role on endothelial function in patients with type 2 diabetes with moderate hyperglycemia.
Devoted fathers or selfish lovers? Conflict between mating effort and parental care in a harem‐defending arachnid
Authors: Alissa L. M. , Muniz D. G. , Machado G.
Published: October 2016

When there is a temporal trade‐off between mating effort and parental care, theoretical models predict that intense sexual selection on males leads to reduced paternal care. Thus, high‐quality males should invest more in mating effort because they have higher chances of acquiring mates, whereas low‐quality males should bias their investment towards parental care. Once paternal care has evolved, offspring value should also influence males’ decisions to invest in offspring attendance. Here, we performed a manipulation under field conditions to investigate the factors that influence male allocation in either mating effort or parental care. We predicted that facultative paternal care in the harem‐holding harvestman Serracutisoma proximum would be negatively influenced by male attractiveness and positively influenced by offspring value. We found that attractive males were less likely to engage in egg attendance and that the higher the perceived paternity, the higher the caring frequency. Finally, egg mortality was not related to caring frequency by males, but predation pressure was much lower than that recorded in previous studies with the same population. Thus, the benefits of facultative male care may be conditional to temporal variation in the intensity of egg predation. In conclusion, males adjust their investment in either territory defence or egg attendance according to their recent mating history and perceived paternity. Our findings suggest that exclusive paternal care can evolve from facultative paternal care only if the trade‐off between mating effort and parental care is circumvented.
Role of C16, angiopoietin‐1 and regeneration gene protein 2 in attenuating inflammation in an experimental rat model of autoimmune encephalomyelitis
Authors: Tian Ke‐Wei , Zhang Fan , Jiang Hong , Wang Beibei , Han Shu
Published: October 2016

Multiple sclerosis (MS) is a chronic neurological disorder that affects the central nervous system (CNS), and results in CNS inflammation and damage to myelin. In this study, we examined the possible synergistic effects of C16, angiopoietin‐1 (Ang‐1) and regeneration gene protein 2 (Reg‐2) in alleviating inflammation in an acute experimental autoimmune encephalomyelitis (EAE) model. We employed multiple histological, morphological and iconographic assays to examine the effect of those drugs on disease onset, clinical scores and behavioral deficits. Our results demonstrated that triple combination therapy was more efficient than the monotherapy in EAE treatment. The triple therapy significantly delayed the onset of motor symptoms, reduced disease severity, attenuated inflammatory cell infiltration and suppressed the secretion of proinflammatory cytokines. Additionally, treatment increased anti‐inflammatory cytokines expression, inhibited reactive astrocytes proliferation, reduced demyelination and axonal loss, and finally reduced the neural death. Specifically, Reg‐2 administration rescued oligodendrocytes and neuronal axons mainly by direct neurotrophic effects, while C16+Ang‐1 (C+A) mainly improved the inflammatory milieu. In conclusion, our study suggests a possible synergistic effect through targeting a variety of pathways in relieving the clinical symptoms of inflammation in acute EAE model. Therefore, using molecules that target different molecular pathways can be beneficial for exploring novel therapeutic approaches for MS treatment.
Dichloroacetate induces regulatory T-cell differentiation and suppresses Th17-cell differentiation by pyruvate dehydrogenase kinase-independent mechanism
Authors: Makita Naoyuki , Ishiguro Jun , Suzuki Keisuke , Nara Futoshi
Published: October 2016

Objectives

Recently, there has been a growing interest in the mechanism of action of dichloroacetate (DCA) for T-cell differentiation; however, this mechanism has not been elucidated in detail. Therefore, this study aimed to investigate the mechanism of action of DCA for Treg and Th17 differentiation with pyruvate dehydrogenase kinase (PDHK) inhibitor (AZD7545) and PDHK knockdown.

Methods

Inhibitory activity of DCA and AZD7545 against recombinant PDHK and intracellular PDH phosphorylation was measured. The effects of DCA and AZD7545 on T-cell differentiation were assessed by analysing Foxp3+ T-cell populations for Treg differentiation and IL-17A production for Th17 differentiation. For reactive oxygen species (ROS) production, DCFDA was used as an indicator.

Key findings

Dichloroacetate and AZD7545 inhibited PDHK activity of recombinant PDHK and intracellular PDH phosphorylation. DCA was capable of inducing Treg differentiation and suppressing Th17 differentiation. The effects of DCA were independent of PDHK because neither AZD7545 nor knockdown of PDHK1 or PDHK3 affected T-cell differentiation. DCA was determined to be capable of inducing ROS production, and the effects of DCA on T-cell differentiation were shown to be dependent on ROS production.

Conclusions

Dichloroacetate possesses Treg induction and Th17 suppression, which is independent of PDHK and dependent on ROS production.
Effects of increasing amount of dietary Prosopis laevigata pods on performance, meat quality and fatty acid profile in growing lambs
Authors: Negrete L. O. , Pinos‐Rodríguez J. M. , Grajales‐Lagunes A. , Morales J. A. , García‐López J. C. , Lee‐Rangel H. A.
Published: October 2016

A study with finishing lambs assessed the effect of dietary inclusion of Prosopis laevigata pods (PLPs) on performance, carcass characteristics, meat traits and fatty acid profile of subcutaneous fat. Twenty‐one Rambouillet lambs (27.0 ± 3.0 kg BW) were assigned to one of three experimental diets with 0, 150 and 300 g PLP/kg DM. Evaluation of growth performance lasted 49 days. The experimental design was completely randomized and analysed with a mixed model. Lambs fed diets with 0, 150 and 300 g PLP had similar growth performance. Lambs fed diets with 300 g PLP/kg DM had better (p < 0.05) carcass yield and classification, less (p < 0.05) fat deposition and lower lightness (L*) value (p < 0.05) in meat than lambs fed diets with 0 and 150 g PLP/kg DM. Saturated fatty acids (palmitic and stearic) decreased (p < 0.05) and unsaturated fatty acids (oleic and linoleic) increased (p < 0.05) in subcutaneous fat of lambs fed diets with 150 and 300 g pods as compared with lambs not fed PLP. Prosopis laevigata pods are a safe feedstuff that can replace a third of conventional ingredients and reduce feed costs in growing lambs. Addition of PLP reduced (p < 0.05) total feed cost by 21%.
Volumetric‐modulated arc stereotactic radiotherapy for canine adrenocortical tumours with vascular invasion
Authors: Dolera M. , Malfassi L. , Pavesi S. , Finesso S. , Sala M. , Carrara N. , Marcarini S. , Mazza G. , Bianchi C. , Urso G.
Published: October 2016

Objectives

To evaluate the feasibility and efficacy of hypofractionated stereotactic volumetric‐modulated arc radiotherapy in treating canine adrenal tumours with vascular invasion.

Methods

A single‐arm clinical study was performed. The dogs underwent total body computed tomography, brain and abdomen magnetic resonance imaging and endocrine assay. Adrenal masses were classified as cortisol‐secreting adrenal tumour or non‐secreting adrenal tumour. Radiotherapy treatments were delivered by hypofractionated stereotactic volumetric‐modulated arc radiotherapy via a linear accelerator. The overall survival was estimated by the Kaplan–Meier method. The overall response and radio‐toxicity effects were determined.

Results

Nine dogs were enrolled. Three dogs were affected by cortisol‐secreting adrenal tumours and the remaining dogs had non‐secreting adrenal tumours. The prescribed doses ranged from 30 to 45 Gy in three or five consecutive daily fractions. The median overall survival time was 1030 days, and the overall mean reduction of the diameter and volume were ~32 and 30% respectively. The endocrine profile normalised in two dogs with cortisol‐secreting adrenal tumours. Radio‐toxicities were mild and self‐limiting. Seven deaths were recorded during the follow‐up period and two dogs were censored.

Clinical Significance

Hypofractionated stereotactic volumetric‐modulated arc radiotherapy should be considered as a feasible and effective therapeutic option for adrenal tumours with vascular invasion.
Low temperature and dust favourin vitrosurvival ofMycoplasma hyopneumoniae: time to revisit indirect transmission in pig housing
Authors: Browne C. , Loeffler A. , Holt H.R. , Chang Y.M. , Lloyd D.H. , Nevel A.
Published: October 2016

Porcine enzootic pneumonia (EP) caused by Mycoplasma hyopneumoniae adversely affects pig welfare and is associated with major economic losses in the pig industry worldwide. Transmission is predominantly by direct contact, but the role of indirect transmission remains poorly understood. This study examined survival of six M. hyopneumoniae isolates dried onto five different surfaces encountered in pig units and exposed to temperatures of 4, 25 and 37°C for up to 12 days. Survival of the organisms was determined by recovering the organism from the surface material and culturing in Friis broth. Data were analysed by logistic regression to identify factors influencing survival of M. hyopneumoniae. Maximum survival was 8 days for all isolates on at least one surface (except stainless steel) at 4°C and was limited to 2 days at 25 and 37°C. Overall, dust and polypropylene copolymer supported M. hyopneumoniae survival the longest when compared with other surface materials. In conclusion, we have demonstrated that M. hyopneumoniae can survive outside the host for at least 8 days.

Significance and Impact of the Study

Understanding the transmission of Mycoplasma hyopneumoniae and optimizing biosecurity practices are keys to reducing the use of antimicrobial agents to control this pathogen. Direct transmission of the pathogen between pigs is the main route of spread and its lack of cell wall may compromise its resilience outside the host. The results from our study show that M. hyopneumoniae can survive for up to several days on dry surfaces and therefore may have the potential to infect pigs by indirect transmission. Factors influencing the survival of M. hyopneumoniae outside the host are further elucidated.
Canine epididymal spermatozoa: A hidden treasure with great potential
Authors: Luvoni GC , Morselli MG
Published: October 2016

Contents

The hidden treasure represented by epididymal spermatozoa has great potential in the current reproductive technologies in dogs. In case of azoospermia or when a donor male accidentally dies or undergoes orchiectomy, the retrieval of epididymal spermatozoa opens new possibilities to generate progeny. Spermatozoa can be collected by different techniques from ex vivo or in vivo testicles and can be cryopreserved for a future use. Freeze tolerance of canine epididymal spermatozoa seems lower than that of ejaculated spermatozoa; however, puppies were born after artificial insemination with frozen epididymal semen, other than with fresh and chilled. Even though several aspects need to be further investigated, advances have been recently made in the use of epididymal spermatozoa in assisted reproduction in dogs.
Diagnostic possibilities from a serum sample—Clinical value of new methods within small animal reproduction, with focus on anti‐Müllerian hormone
Authors: Holst BS
Published: October 2016

Contents

During the last decade, analysis of anti‐Müllerian hormone (AMH), highly conserved between mammalian species, has contributed to new information in reproductive endocrinology, due to clinically available diagnostic assays. AMH is produced solely in the gonads, in the Sertoli cells of testes and granulosa cells of the ovary, and thus offers possibilities to diagnose physiologic and pathologic conditions involving these organs. This article reviews indications for AMH analysis in cats and dogs, including diagnosing the presence of gonads, and granulosa or Sertoli cell tumours. Diagnostic challenges are addressed. One specific organ, the prostate, is commonly affected by pathologic changes in older dogs. A commercial assay for analysing canine prostatic specific esterase (CPSE) enables analysis of CPSE in clinical practice, of potential value in the workup of benign prostatic hyperplasia in male dogs. This is described in this review, as is a new method for analysis of steroids: liquid chromatography‐tandem mass spectrometry LC‐MS/MS. Steroids have since long been analysed in studies on reproduction, and LC‐MS/MS has the advantage of allowing analysis of panels of multiple steroids from small sample volumes. Altogether, these available methods may give new insights into small animal reproduction and are valuable tools for the practicing veterinarian.
Complex Applications of HLM in Studies of Science and Mathematics Achievement: Cross‐Classified Random Effects Models
Authors: Moreno Mario , Harwell Michael , Guzey S. Selcen , Phillips Alison , J. Moore Tamara
Published: October 2016

Hierarchical linear models have become a familiar method for accounting for a hierarchical data structure in studies of science and mathematics achievement. This paper illustrates the use of cross‐classified random effects models (CCREMs), which are likely less familiar. The defining characteristic of CCREMs is a hierarchical data structure defined by multiple random factors at higher levels. We illustrate CCREMs using data for approximately 10,000 students from more than 250 high schools who attended one of 27 four‐year postsecondary institutions. The appropriate use of CCREMs helps to ensure unbiased estimates of effects and credible inferences.
Non‐Tariff Measures, Specific Trade Concerns and Tariff Reduction
Authors: Orefice Gianluca
Published: October 2016

This paper studies the determinants of the recent proliferation of Specific Trade Concerns raised at the WTO on non‐tariff trade measures (NTMs), with a focus on sanitary and phytosanitary (SPS) and technical barriers to trade (TBTs). Even though NTMs are imposed de jure to protect consumers from unhealthy products, they increase trade costs de facto. So, when tariff protection lowers, NTMs become effective barriers to trade and the exporting countries can complain at the dedicated committee at the WTO (STCs). Therefore, we study whether STCs are raised by exporting countries as a consequence of tariff reductions in importing countries, that is when non‐tariff measures become barriers to trade. Using a recent database on STCs over the period 1996–2010, we find empirical evidence that SPS and TBT concerns are raised by exporting country as a consequence of importer's tariff cut.
Modelling gas exchange during platelet storage without agitation
Authors: Torres R. , Tormey C. A.
Published: October 2016

The aim of this study was to create a model of oxygen distribution within platelet storage bags to evaluate implications of reduced agitation approaches. Based on our model, platelet concentration and surface area most affect internal partial pressure of oxygen, while temperature modifications have least effect, indicating primary potential approaches for optimization of platelet storage with reduced or absent agitation.
Prophylactic RhCE and Kell antigen matching: impact on alloimmunization in transfusion‐dependent patients with myelodysplastic syndromes
Authors: Lin Y. , Saskin A. , Wells R. A. , Lenis M. , Mamedov A. , Callum J. , Buckstein R.
Published: October 2016

Background and Objectives

Thirty to 80 per cent of patients with myelodysplastic syndromes (MDS) become transfusion‐dependent and are at risk for red blood cell (RBC) alloimmunization. This study compared alloimmunization rates in transfusion‐dependent patients with MDS at an institution with a policy of prophylactic antigen matching for RhCE and K (PAM) with those transfused at institutions without such a policy (non‐PAM).

Materials and Methods

Transfusion records were retrospectively reviewed to determine total number of RBC transfusions received, whether RBC phenotyping was performed, the type and date of first alloantibody development and receipt of prophylactic antigen matching for RhCE and K.

Results

In 176 transfusion‐dependent patients with MDS, the overall rate of new alloimmunization was 17%; the majority of patients (87%) developed at least one alloantibody to Rh or Kell antigens. The alloimmunization rate at the institution with a PAM policy was 11% compared with 23% at non‐PAM institutions (P = 0·06). The rate of Rh/K alloimmunization was 7 vs. 22%, respectively (P = 0·008). No patient who received PAM developed a Rh/K alloantibody.

Conclusion

The rate of alloimmunization was 11% at an institution with a PAM policy which was non‐significantly lower than 23% at institutions without a PAM policy. However, rates of Rh/K alloimmunization were significantly lower. Such a policy should be considered in transfusion‐dependent patients with MDS, although further studies on cost‐effectiveness and careful consideration of resource availability in the local context are required.
Serum soluble urokinase‐type plasminogen activator receptor as a serum marker of inflammatory response that leads to tissue damage and surgical complication
Authors: Tognoli Emiliano , Luigi Giuseppe Leoni Matteo , Morelli Daniele , Sottotetti Elisa , Martinetti Antonia , Signoroni Stefano , Galeone Carlotta , Gallino Gianfranco
Published: October 2016

Unrestrained activation of the proteolytic systems in anastomotic tissue during repair has been implicated in the pathogenesis of anastomotic leakage. We hypothesized that this mechanism may promote an up‐regulation of the urokinase‐type plasminogen activator system and a spillover of soluble urokinase‐type plasminogen activator receptor (suPAR) into blood. In this retrospective analysis patients with anastomotic leakage were compared with a group of matched uncomplicated patients. Anastomotic leakage complicated patients had significantly higher suPAR (p = 0.04) levels until day 3 after surgery. The area under the receiver‐operating characteristic (ROC) for suPAR was higher than that CRP (0.874 vs. 0.836). Their analysis suggests the possible use of suPAR as serum marker to characterize the persistent inflammatory response that lead to tissue damage and surgical complication.
Edge Debonding in Peeling of a Thin Flexible Plate From an Elastomer Layer: A Cohesive Zone Model Analysis
Authors: Mukherjee Bikramjit , Batra Romesh C. , Dillard David A.
Published: October 2016

A cohesive zone modeling (CZM) approach with a bilinear traction-separation relation is used to study the peeling of a thin overhanging plate from the edge of an incompressible elastomeric layer bonded firmly to a stationary rigid base. The deformations are approximated as plane strain and the materials are assumed to be linearly elastic, homogeneous, and isotropic. Furthermore, governing equations for the elastomer deformations are simplified using the lubrication theory approximations, and those of the plate with the Kirchhoff–Love theory. It is found that the peeling is governed by a single nondimensional number defined in terms of the interfacial strength, the interface fracture energy, the plate bending rigidity, the elastomer shear modulus, and the elastomeric layer thickness. An increase in this nondimensional number monotonically increases the CZ size ahead of the debond tip, and the pull-off force transitions from a fracture energy to strength dominated regime. This finding is supported by the results of the boundary value problem numerically studied using the finite element method. Results reported herein could guide elastomeric adhesive design for load capacity and may help ascertain test configurations for extracting the strength and the fracture energy of an interface from test data.
Immersive Distributed Design Through Real-Time Capture, Translation, and Rendering of Three-Dimensional Mesh Data1
Authors: Lesniak Kevin , Terpenny Janis , Tucker Conrad S. , Anumba Chimay , Bilén Sven G.
Published: October 2016

With design teams becoming more distributed, the sharing and interpreting of complex data about design concepts/prototypes and environments have become increasingly challenging. The size and quality of data that can be captured and shared directly affects the ability of receivers of that data to collaborate and provide meaningful feedback. To mitigate these challenges, the authors of this work propose the real-time translation of physical objects into an immersive virtual reality environment using readily available red, green, blue, and depth (RGB-D) sensing systems and standard networking connections. The emergence of commercial, off-the-shelf RGB-D sensing systems, such as the Microsoft Kinect, has enabled the rapid three-dimensional (3D) reconstruction of physical environments. The authors present a method that employs 3D mesh reconstruction algorithms and real-time rendering techniques to capture physical objects in the real world and represent their 3D reconstruction in an immersive virtual reality environment with which the user can then interact. Providing these features allows distributed design teams to share and interpret complex 3D data in a natural manner. The method reduces the processing requirements of the data capture system while enabling it to be portable. The method also provides an immersive environment in which designers can view and interpret the data remotely. A case study involving a commodity RGB-D sensor and multiple computers connected through standard TCP internet connections is presented to demonstrate the viability of the proposed method.
Unwrapping 3D complex hollow organs for spatial dose surface analysis
Authors: Witztum A. , George B. , Warren S. , Partridge M. , Hawkins M. A.
Published: October 2016

Purpose

Toxicity dose–response models describe the correlation between dose delivered to an organ and a given toxic endpoint. Duodenal toxicity is a dose limiting factor in the treatment of pancreatic cancer with radiation but the relationship between dose and toxicity in the duodenum is not well understood. While there have been limited studies into duodenal toxicity through investigations of the volume of the organ receiving dose over a specific threshold, both dose‐volume and dose‐surface histograms lack spatial information about the dose distribution, which may be important in determining normal tissue response. Due to the complex geometry of the duodenum, previous methods for unwrapping tubular organs for spatial modeling of toxicity are insufficient. A geometrically robust method for producing 2D dose surface maps (DSMs), specifically for the duodenum, has been developed and tested in order to characterize the spatial dose distribution.

Methods

The organ contour is defined using Delaunay triangulation. The user selects a start and end coordinate in the structure and a path is found by regulating both length and curvature. This path is discretized and rays are cast from each point on the plane normal to the vector between the previous and the next point on the path and the dose at the closest perimeter point recorded. These angular perimeter slices are “unwrapped” from the edge distal to the pancreas to ensure the high dose region (proximal to the tumor) falls in the centre of the dose map. Gamma analysis is used to quantify the robustness of this method and the effect of overlapping planes.

Results

This method was used to extract DSMs for 15 duodena, with one esophagus case to illustrate the application to simpler geometries. Visual comparison indicates that a 30 × 30 map provides sufficient resolution to view gross spatial features of interest. A lookup table is created to store the area (cm2) represented by each pixel in the DSMs in order to allow spatial descriptors in absolute size. The method described in this paper is robust, requires minimal human interaction, has been shown to be generalizable to simpler geometries, and uses readily available commercial software. The difference seen in DSMs due to overlapping planes is large and justifies the need for a solution that removes such planes.

Conclusions

This is the first time 2D dose surface maps have been produced for the duodenum and provide spatial dose distribution information which can be explored to create models that may improve toxicity prediction in treatments for locally advanced pancreatic cancer.