bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of effectiveness and safety of excimer lamp vs topical calcipotriol‐clobetasol propionate combination in the treatment of palmoplantar psoriasis
Authors: Thakur Abhishek , Bishnoi Anuradha , Dogra Sunil , Narang Tarun
Published: February 2018

Background

Very few studies have assessed the efficacy of excimer in the treatment of palmoplantar psoriasis (PPP), and none has compared the excimer with calcipotriol‐clobetasol propionate combination.

Purpose

To compare the effectiveness and safety of excimer lamp vs topical ointment containing calcipotriol (0.005% w/w) and clobetasol propionate (0.05% w/w) combination in PPP.

Methods

This right‐left randomization trial included 36 patients with PPP, who received treatment with excimer lamp (twice weekly) on one side and calcipotriol‐clobetasol combination (once daily) on another side for 12 weeks, followed by 8 weeks of follow‐up. Recruitment and response assessment was done by 2 experienced dermatologists (SD and TN) using modified palmoplantar pustular psoriasis area and severity index score (mPPPASI, originally devised for palmoplantar pustulosis, suitably modified to assess response in PPP).

Primary outcome measure was percentage improvement in mPPPASI at 12 weeks, which was classified as minimal (≤25%), mild (>25%‐50%), moderate (>50%‐75%), and marked (>75%). Secondary outcome measures were the proportion of patients achieving >75% reduction in mPPPASI and the time taken to achieve it.

Results

Of 36 recruited patients, 33 completed treatment and 21 adhered to 8‐weeks follow‐up. The mean mPPPASI on the excimer‐treated sides reduced significantly from 7.75 ± 4.62 to 4.01 ± 4.07 (P < .001) at 12th week (end of the treatment) and 2.66 ± 3.97 at 20th week (at 8 weeks follow‐up). The mean mPPPASI on the calcipotriol‐clobetasol combination treated sides reduced significantly from 7.36 ± 4.46 to 3.55 ± 3.77 (P < .001) and 2.70 ± 3.97 at 12th week and 20th week, respectively. The reduction was significant for both treatment and the difference between the two was not statistically significant.

Minimal, mild, moderate, and marked improvement was seen in 5/33 (15.2%) and 1/33 (3.0%), 6/33 (18.2%) and 8/33 (24.2%), 12/33 (36.4%) and 13/33 (39.4%), and 8/33 (24.2%) and 8/33 (24.2%) sides in the excimer and calcipotriol‐clobetasol combination, respectively. A total of 8 patients in each group achieved mPPPASI 75 at 12 weeks. The mPPPASI 75 was achieved at 2, 4, and 8 weeks in 1, 2, and 8 patients, respectively, using either modalities. The adverse effects (most commonly hyperpigmentation) were noted more frequently on the excimer‐treated sides; however, they were well tolerated.

Conclusion

Both excimer lamp and calcipotriol‐clobetasol propionate combination are equally effective in the treatment of PPP.
A novel Meloidogyne incognita chorismate mutase effector suppresses plant immunity by manipulating the salicylic acid pathway and functions mainly during the early stages of nematode parasitism
Authors: Wang X. , Xue B. , Dai J. , Qin X. , Liu L. , Chi Y. , Jones J. T. , Li H.
Published: February 2018

Meloidogyne incognita is the most economically important plant‐parasitic nematode. Meloidogyne incognita manipulates plant cell development and metabolism by injecting effectors from the oesophageal glands into the plant host. Chorismate mutase (CM) is one such effector that may contribute to successful parasitism by M. incognita. This investigation identified and functionally characterized a novel CM effector, Mi‐CM‐3, which is more similar to CMs from bacteria than from other phytoparasitic nematodes. Spatial and temporal expression assays showed Mi‐cm‐3 mRNA accumulates specifically in the subventral oesophageal glands and transcription is up‐regulated during the early parasitic stages of the nematode. In planta gene silencing of Mi‐cm‐3 attenuated nematode parasitism. In addition, Mi‐cm‐3 could fully restore the full virulence phenotype of the pathogenic bacterium Xanthomonas oryzae pv. oryzae by complementation when it was introduced into a mutant strain carrying a deletion in the CM gene. Transient expression of Mi‐CM‐3 caused a reduction in levels of salicylic acid (SA) and mRNA of gene PR1 in Nicotiana benthamiana in response to oomycete pathogen Phytophthora capsici infection, while confocal observations showed that Mi‐CM‐3 was localized within the cytoplasm and the nucleus, but not the plastids, of transfected N. benthamiana leaf cells. Constitutive expression of Mi‐CM‐3 in N. benthamiana plants inhibited root growth and increased susceptibility to M. incognita infection. These results provide direct experimental evidence to show that Mi‐CM‐3 may play an important role in suppressing plant immunity by regulating the SA pathway during the early parasitic stage of M. incognita so as to promote nematode parasitism.
Cognitive impairment in Parkinson's disease, Alzheimer's dementia, and vascular dementia: the role of the clock‐drawing test
Authors: Allone Cettina , Lo Buono Viviana , Corallo Francesco , Bonanno Lilla , Palmeri Rosanna , Di Lorenzo Giuseppe , Marra Angela , Bramanti Placido , Marino Silvia
Published: February 2018

Aim

Cognitive impairment is present in several neurodegenerative disorders. The clock‐drawing test (CDT) represents a useful screening instrument for assessing the evolution of cognitive decline. The aim of this study was to investigate the sensitivity of the CDT in monitoring and differentiating the evolution of cognitive decline in Alzheimer's dementia (AD), vascular dementia (VaD), and Parkinson's disease (PD).

Methods

This study involved 139 patients, including 39 patients with PD and mild cognitive impairment, 16 demented PD patients, 21 VaD patients with mild cognitive impairment, 17 patients with VaD, 33 patients with mild cognitive impairment due to AD, and 13 patients with probable AD. All participants completed the CDT. The Mini‐Mental State Examination was administered to establish patients’ cognitive functioning.

Results

Comparisons of quantitative and qualitative CDT scores showed significant differences between the various diseases. Impairment of executive functioning seems to be more pronounced in PD and VaD than in AD. Patients with AD committed more errors related to a loss of semantic knowledge, indicating a severely reduced capacity in abstract and conceptual thinking.

Conclusion

Results support the usefulness and sensitivity of the CDT in the detection of different dementia subtypes. Qualitative error analysis of the CDT may be helpful in differentiating PD, VaD, and AD, even in the early stages of each disease.
Profiling of miRNAs in neonatal cloned bovines with collapsed lungs and respiratory distress
Authors: Zhang FY , Yang N , Rao YF , Du WH , Hao HS , Zhao XM , Zhu HB , Liu Y
Published: February 2018

Contents

Neonatal respiratory distress is a major mortality factor in cloned animals; however, the pathogenesis of this disease has rarely been investigated. Previous studies have shown that miRNAs regulate critical genes related to lung development, cell differentiation, surfactant synthesis, secretion and lung disease. This study aimed to examine differentially expressed miRNAs in collapsed lungs of cloned bovine neonates and normal lungs in order to identify key pathways and functions that might be related to the pathogenesis of neonatal respiratory distress. In this study, miRNA transcriptomes of collapsed lungs of neonatal cloned bovines and normal lungs were analysed by next‐generation sequencing and the results were validated using quantitative real‐time PCR (qRT‐PCR). A total of 177 differentially expressed miRNAs were identified in the two groups (fold change > 2, RPM ≥ 5), some of which were associated with type II cell differentiation, for example, mmu‐miR‐29a‐5p_L‐2R+1, hsa‐miR‐200c‐5p_L‐1R+1 and mmu‐miR‐18a‐3p_R+1. The differentially expressed miRNAs were predicted to 6,031 target genes. By Gene Ontology (GO) and Kyoto Encyclopeida of Genes and Genomes (KEGG) DATA base, 133 significant GO terms (p < .05) and 13 significant KEGG pathways (p < .05) were obtained. Many of them were associated with lung development and surfactant homoeostasis, such as lipid biosynthetic processes, protein transport, endocytosis, lysosome, endosome, Golgi apparatus and membrane. Our results of miRNAs express profiles may partially explain the respiratory distress and lung collapse in neonatal bovine clones and could provide novel insights into roles of miRNAs in regulation of lung collapse and neonatal respiratory distress in cloned farm animals.
Functional proteomic analysis of crossbred (Holstein Friesian × Sahiwal) bull spermatozoa
Authors: Singh R , Sengar GS , Singh U , Deb R , Junghare V , Hazra S , Kumar S , Tyagi S , Das AK , Raja TV , Kumar A
Published: February 2018

Contents

Male infertility is one of the prime concerns of dairy cattle production. The study was designed to find out differentially expressed proteins in categorized crossbred (Holstein Friesian × Sahiwal) bull semen to serve as potential biomarkers for male infertility. Frozen crossbred bull semen with satisfactory phenotypic records were defined as “good” and “poor” based on their fertility rates. A total of 1,547 proteins were detected in bull spermatozoa using liquid chromatography–mass spectrometer (LC‐MS/MS) analysis. Results revealed that 558 (36.1%) and 653 (42.2%) proteins were expressed to good and poor quality bull spermatozoa, respectively. A total of 336 proteins (21.7%) were reported to be unique for both good and poor quality bull semen, and among the common proteins, 224 (66.7%) and 112 (33.3%) were up‐ and downregulated in good and poor quality categorized bull semen, respectively. Gene Ontology analysis of global proteomes identified different signalling pathways, and most of them were related to cellular motility, immune systems as well as cellular metabolisms. The distinctive presence of some of the proteins may provide an insight into the molecular mechanistic role played by these proteins in crossbred bull infertility.
Social innovation, social enterprise, and local public services: Undertaking transformation?
Authors: Sinclair Stephen , Mazzei Micaela , Baglioni Simone , Roy Michael J.
Published: February 2018

This article discusses some of the challenges encountered in embedding effective and sustainable social enterprise and social innovation within established political institutional systems to deliver local welfare services. It draws upon evidence analyzing social innovation and social enterprise in Scotland to contribute to the debate over whether social innovations and social enterprises are able to meet expectations in addressing the significant challenges faced by welfare systems. The article clarifies the meaning of both these contested concepts and explains how social innovation and social enterprise relate to similar ideas in social and public policy. The evidence suggests that actually operating social enterprises and social innovations do not embrace the image of them promoted by enthusiasts as either “entrepreneurial” or “innovative”. Furthermore, they bring distinctive challenges in delivering local welfare services, including potential tensions or rivalry with existing public agencies. The article suggests that social enterprises and social innovations are not themselves instigators nor catalysts for systemic change, but that their impact is constrained by structural conditions and institutional factors beyond their control.
Allopolyploidization in Cucumis contributes to delayed leaf maturation with repression of redundant homoeologous genes
Authors: Yu Xiaqing , Wang Xixi , Hyldgaard Benita , Zhu Zaobing , Zhou Rong , Kjær Katrine Heinsvig , Ouzounis Theoharis , Lou Qunfeng , Li Ji , Cai Qingsheng , Rosenqvist Eva , Ottosen Carl‐Otto , Chen Jinfeng
Published: February 2018

The important role of polyploidy in plant evolution is widely recognized. However, many questions remain to be explored to address how polyploidy affects the phenotype of the plant. To shed light on the phenotypic and molecular impacts of allopolyploidy, we investigated the leaf development of a synthesized allotetraploid (Cucumis × hytivus), with an emphasis on chlorophyll development. Delayed leaf maturation was identified in C. × hytivus, based on delayed leaf expansion, initial chlorophyll deficiency in the leaves and disordered sink‐source transition. Anatomical observations also revealed disturbed chloroplast development in C. ×hytivus. The determination of chlorophyll biosynthesis intermediates suggested that the chlorophyll biosynthesis pathway of C. × hytivus is blocked at the site at which uroporphyrinogen III is catalysed to coproporphyrinogen III. Three chlorophyll biosynthesis‐related genes, HEMA1, HEME2 and POR, were significantly repressed in C. × hytivus. Sequence alignment showed both synonymous and non‐synonymous substitutions in the HEMA1, HEME2 and POR genes of the parents. Cloning of the chlorophyll biosynthetic genes suggested the retention of homoeologs. In addition, a chimeric clone of the HEMA1 gene that consisted of homologous genes from the parents was identified in C. × hytivus. Overall, our results showed that allopolyploidization in Cucumis has resulted in disturbed chloroplast development and reduced chlorophyll biosynthesis caused by the repressed expression of duplicated homologous genes, which further led to delayed leaf maturation in the allotetraploid, C. × hytivus. The preferential retention/loss of certain types of genes and non‐reciprocal homoeologous recombination were also supported in the present study, which provides new insights into the impact of allopolyploidy.
Treatment of acute kidney injury associated with cyclosporine overdose in a dog using hemodialysis and charcoal hemoperfusion
Authors: Segev Gilad , Cowgill Larry D.
Published: February 2018

Objective

To describe the management of cyclosporine overdose using hemodialysis and hemoperfusion in a dog.

Case Summary

A 6‐year‐old, spayed female Australian Shepherd was presented for treatment of cyclosporine overdose and acute kidney injury. Five days prior to presentation, the dog had been diagnosed by its referring veterinarian with immune‐mediated thrombocytopenia. Treatment was initiated with prednisone, but since no response was noted, azathioprine (50 mg PO q 24 h) and cyclosporine (6 mg/kg IV q 24 h) were added. On day 4, an overdose of cyclosporine (33 mg/kg IV) was administered accidentally. Upon presentation, serum biochemistry panel revealed azotemia [creatinine, 521.6 μmol/L (5.9 mg/dL); BUN, 59.3 mmol/L (166 mg/dL)], increased activities of liver enzymes, and hyperbilirubinemia. Due to the presumed diagnosis cyclosporine overdose and acute kidney injury, a combined hemodialysis and charcoal hemoperfusion treatment was planned. Hemosorba CH‐350 charcoal hemoperfusion cartridge was placed in series upstream in the extracorporeal circuit from the hemodialyzer. A 3‐hour treatment was performed and a total of 0.74 L/kg of blood was processed. Pretreatment blood cyclosporine concentration was 960 nmol/L (1154 ng/mL) and decreased to 440 nmol/L (529 ng/mL) posttreatment (54% fractional reduction, 18% per hour). Thirty‐one hours following treatment, blood cyclosporine concentration was 220 nmol/L (265 ng/mL; 1.5% decrease per hour). Twelve days following presentation to our hospital, the dog was euthanized due to lack of response to medical management.

New or Unique Information Provided

Combined hemodialysis and charcoal hemoperfusion treatment can significantly reduce blood cyclosporine concentrations following acute intoxication or overdosage, and should be considered as an option for decontamination in such cases.
Evaluation of nafamostat mesilate as an alternative anticoagulant during intermittent hemodialysis in healthy Beagle dogs
Authors: Choi Joon‐hyuk , Byun Seok‐yeong , Nam Aryung , Han Sei‐myoung , Lee Kyu‐pil , Song Kun‐ho , Youn Hwa‐young , Seo Kyoung‐won
Published: February 2018

Objective

To evaluate nafamostat mesilate (NM) as an alternative anticoagulant agent for intermittent hemodialysis (IHD).

Design

Prospective randomized study.

Setting

University teaching hospital.

Animals

Eighteen healthy Beagle dogs.

Interventions

In group 1 (n = 6), NM was administered at a dose of 0.5 mg/kg/h during IHD for 5 hours. In group 2 (n = 6), NM was administered at a low dose of 0.25 mg/kg/h during IHD. In group 3 (n = 6), which was the control group, unfractionated heparin (UFH) was administered during IHD. The evaluated parameters included: the amount of residual blood clots in the blood chamber and arterial side of the dialyzer; the levels of hemoglobin, hematocrit, and platelets; and the prothrombin time (PT), activated partial thromboplastin time (aPTT), and activated clotting time (ACT).

Measurements and Main Results

Groups 1 and 2 successfully completed IHD without serious coagulation in the extracorporeal circulation. The residual blood clotting in the blood chamber and arterial side of the dialyzer did not significantly differ in groups 1 and 2 compared to group 3 (group 1 vs group 3, P = 1.000; and group 2 vs group 3, P = 1.000). No significant differences were observed between pre‐ and posttreatment PTs in groups 1 (P = 0.476) and 2 (P = 0.597), between pre‐ and posttreatment aPTTs in groups 1 (P = 0.983) and 2 (P = 0.977), and between pre‐ and posttreatment ACT in groups 1 (P = 0.282) and 2 (P = 0.401). In group 3, a significant elevation of ACT was observed at the posttest (P < 0.001).

Conclusions

The results of this study in healthy Beagle dogs suggest that NM at 0.25 mg/kg/h may be a valid alternative to UFH for IHD. Further studies are needed in patients at high risk of bleeding.
Constitutive overexpression of periostin delays wound healing in mouse skin
Authors: Nunomura Satoshi , Nanri Yasuhiro , Ogawa Masahiro , Arima Kazuhiko , Mitamura Yasutaka , Yoshihara Tomohito , Hasuwa Hidetoshi , Conway Simon J. , Izuhara Kenji
Published: February 2018

Periostin is a matricellular protein involved in development, maintenance, and regulation of tissues and organs via by binding to cell surface integrin receptors. Pathologically, periostin plays an important role in the process of wound healing: as a deficiency of the Postn gene delays wound closure and periostin is consistently up‐regulated in response to injury and skin diseases. However, the functional role of elevated periostin in the process of wound healing has not been tested. In this study, we generated Postn‐transgenic mice under the control of the CAG promoter/enhancer to investigate the effects of constitutive overexpression of full length periostin during its pathophysiological roles. Transgenic mice showed significant overexpression of periostin in skin, lung, and heart, but no morphological changes were observed. However, when these transgenic mice were injured, periostin overexpression delayed the closure of excisional wounds. Expression of IL‐1β and TNFα, pro‐inflammatory cytokines important for wound healing, was significantly decreased in the transgenic mice, prior to delayed healing. Infiltration of neutrophils and macrophages, the main sources of IL‐1β and TNFα, was also down‐regulated in the transgenic wound sites. From these data, we conclude that enforced expression of periostin delays wound closure due to reduced infiltration of neutrophils and macrophages followed by down‐regulation of IL‐1β and TNFα expression. This suggests that regulated spatiotemporal expression of periostin is important for efficient wound healing and that constitutive periostin overexpression interrupts the normal process of wound closure.
Heterogeneous Nonlinear Systems Synchronization Based on Adaptive Super Twisting
Authors: Salas-Peña Oscar , De León-Morales Jesús
Published: February 2018

In this work, the synchronization of a group of heterogeneous uncertain nonlinear systems is addressed. A strategy based on adaptive super twisting algorithm is proposed, in order to synchronize the outputs of the heterogeneous systems. With the aim of implementing the proposed control strategy, unmeasurable states are estimated by means of high-order sliding modes differentiators. This control scheme increases robustness against unknown dynamics and disturbances, whose bounds are not required to be known. Finally, experimental results for synchronizing a heterogeneous system platform, constituted by an inertial stabilization platform (ISP) and a helicopter of two degrees-of-freedom (DOF), are used to illustrate the performance of the proposed control scheme.
Determination of Motor Torque for Power-Assist Electric Bicycles Using Observer-Based Sensor Fusion
Authors: Huang Chun-Feng , Dai Bang-Hao , Yeh T.-J.
Published: February 2018

This paper proposes a sensor fusion algorithm to determine the motor torque for power-assist electric bicycles. Instead of using torque sensors to directly measure the pedaling torque, outputs from a wheel encoder and a six-axis inertial measurement unit (IMU) are processed by the fusion algorithm to estimate the slope angle of the road and the longitudinal acceleration of the bicycle for conducting mass compensation, gravity compensation, and friction compensation. The compensations allow the ride of the electric bicycle on hills to be as effortless as the ride of a plain bicycle on the level ground regardless of the weight increase by the battery and the motor. The sensor fusion algorithm is basically an observer constructed on the kinematic model which describes the time-varying characteristics of the gravity vector observed from a frame moving with the bicycle. By exploiting the structure of the observer model, convergence of the estimation errors can be easily achieved by selecting two constant, subgain matrices in spite of the time-varying characteristics of the model. The validity of the sensor fusion is verified by both numerical simulations and experiments on a prototype bicycle.
The spider mites of the genus Oligonychus Berlese (Acari: Tetranychidae) from Iran
Authors: Khanjani Masoumeh , Khanjani Mohammad , Seeman Owen
Published: February 2018

Two new species of the genus Oligonychus Berlese, namely O. shojaeii sp. nov. and O. hamedaniensis sp. nov., are described from plane trees, Platanus orientalis L. (Platanaceae), in Hamedan, Hamedan province, Iran. Four species are re-described based on new Iranian material: O. afrasiaticus (McGregor, 1939), O. coniferarum (McGregor, 1950), O. punicae (Hirst, 1926) and O. saccharinus Baker & Pritchard, 1960. Among them O. saccharinus is the most important pest on sugarcane farms in southern Iran. All active life stages are described for all species except O. afrasiaticus, allowing us to confirm the ontogenetic patterns of leg setae in the Tetranychini. We refine the definition of the ununguis species group and discuss taxonomic problems relating to the members of this species group, and also regarding the identification of O. sacchari (McGregor, 1942) and O. saccharinus.
Latest improvements in isotopic uranium particle analysis by large geometry–secondary ion mass spectrometry for nuclear safeguards purposes
Authors: Hedberg P. M. L. , Peres P. , Fernandes F. , Albert N. , Vincent C.
Published: February 2018

Large geometry secondary ion mass spectrometry can be efficiently used to analyze uranium aerosol particles from dust samples in the search for undeclared nuclear activities. Automated sample screening measurements are followed by more precise and accurate microbeam measurements of both the major and minor uranium isotopes on selected individual particles. The quality of this work is essential in order to be able to draw valuable safeguards conclusions. This paper describes the latest developments that have been undertaken to enhance the detection limits and to reduce the uranium isotope measurement uncertainty. It includes improvements in the analytical protocol as well as in the instrument acquisition software and data reduction method. Recent useful yield measurements have been performed on uranium monodispersed particles using different primary bombardment conditions to compare to previously obtained data. Comparison of uranium isotope measurements when using pyrolytic graphite or silica planchets as a sample substrate will also be presented.
Children’s Compliance With Wrist-Worn Accelerometry Within a Cluster-Randomized Controlled Trial: Findings From the Healthy Lifestyles Programme
Authors: Price Lisa , Wyatt Katrina , Lloyd Jenny , Abraham Charles , Creanor Siobhan , Dean Sarah , Hillsdon Melvyn
Published: February 2018

Purpose: The purpose of this study was to assess children’s compliance with wrist-worn accelerometry during a randomized controlled trial and to examine whether compliance differed by allocated condition or gender. Methods: A total of 886 children within the Healthy Lifestyles Programme trial were randomly allocated to wear a GENEActiv accelerometer at baseline and 18-month follow-up. Compliance with minimum wear-time criteria (≥10 h for 3 weekdays and 1 weekend day) was obtained for both time points. Chi-square tests were used to determine associations between compliance, group allocation, and gender. Results: At baseline, 851 children had usable data, 830 (97.5%) met the minimum wear-time criteria, and 631 (74.1%) had data for 7 days at 24 hours per day. At follow-up, 789 children had usable data, 745 (94.4%) met the minimum wear-time criteria, and 528 (67%) had complete data. Compliance did not differ by gender (baseline: χ2 = 1.66, P = .2; follow-up: χ2 = 0.76, P = .4) or by group at follow-up (χ2 = 2.35, P = .13). Conclusion: The use of wrist-worn accelerometers and robust trial procedures resulted in high compliance at 2 time points regardless of group allocation, demonstrating the feasibility of using precise physical activity monitors to measure intervention effectiveness.
Persistent producer-scrounger relationships in bats
Authors: Harten Lee , Matalon Yasmin , Galli Naama , Navon Hagit , Dor Roi , Yovel Yossi
Published: February 2018

Bats exhibit persistent social foraging (producer-scrounger) ties.
UV-B–induced forest sterility: Implications of ozone shield failure in Earth’s largest extinction
Authors: Benca Jeffrey P. , Duijnstee Ivo A. P. , Looy Cindy V.
Published: February 2018

UV-B regimes modeled for Earth’s largest mass extinction sterilize living conifers.
Anomalous K-Pg–aged seafloor attributed to impact-induced mid-ocean ridge magmatism
Authors: Byrnes Joseph S. , Karlstrom Leif
Published: February 2018

A global anomaly in seafloor structure is attributed to mid-ocean ridge magmatism triggered by the Chicxulub meteorite impact.
Islet-reactive CD8
+
T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors
Authors: Culina Slobodan , Lalanne Ana Ines , Afonso Georgia , Cerosaletti Karen , Pinto Sheena , Sebastiani Guido , Kuranda Klaudia , Nigi Laura , Eugster Anne , Østerbye Thomas , Maugein Alicia , McLaren James E. , Ladell Kristin , Larger Etienne , Beressi Jean-Paul , Lissina Anna , Appay Victor , Davidson Howard W. , Buus Søren , Price David A. , Kuhn Matthias , Bonifacio Ezio , Battaglia Manuela , Caillat-Zucman Sophie , Dotta Francesco , Scharfmann Raphael , Kyewski Bruno , Mallone Roberto ,   ImMaDiab Study Group, Carel Jean-Claude , Tubiana-Rufi Nadia , Martinerie Laetitia , Poidvin Amélie , JacqzAigrain Evelyne , Corvez Laurence , Berruer Véronique , Gautier Jean-François , Baz Baz , Haddadi Nassima , Andreelli Fabrizio , Amouyal Chloé , Jaqueminet Sophie , Bourron Olivier , Dasque Eric , Hartemann Agnès , Lemoine-Yazigi Amal , Dubois-Laforgue Danièle , Travert Florence , Feron Marilyne , Rolland Patrice , Vignali Valérie , Marre Michel , Chanson Philippe , Briet Claire , Guillausseau Pierre-Jean , Ait-Bachir Leila , Collet Carole , Beziaud Frédéric , Desforges-Bullet Virginie , Petit-Aubert Gwenaelle , Christin-Maitre Sophie , Fève Bruno , Vatier Camille , Bourcigaux Nathalie , Lautridou Céline , Lahlou Najiba , Bakouboula Prissile , Elie Caroline , Morel Hélène , Treluyer Jean-Marc , Gagnerault Marie-Claude , Maillard Claire , Jones Anna
Published: February 2018

Islet-reactive CD8
+
T cells are common in the periphery, but home to the pancreas preferentially in the context of type 1 diabetes.
Targeting p53-dependent stem cell loss for intestinal chemoprotection
Authors: Leibowitz Brian J. , Yang Liheng , Wei Liang , Buchanan Monica E. , Rachid Madani , Parise Robert A. , Beumer Jan H. , Eiseman Julie L. , Schoen Robert E. , Zhang Lin , Yu Jian
Published: February 2018

Targeting of p53- and PUMA-dependent apoptosis protects intestinal stem cells, but not cancer cells, against chemotherapy.
Histone deacetylase activity governs diastolic dysfunction through a nongenomic mechanism
Authors: Jeong Mark Y. , Lin Ying H. , Wennersten Sara A. , Demos-Davies Kimberly M. , Cavasin Maria A. , Mahaffey Jennifer H. , Monzani Valmen , Saripalli Chandrasekhar , Mascagni Paolo , Reece T. Brett , Ambardekar Amrut V. , Granzier Henk L. , Dinarello Charles A. , McKinsey Timothy A.
Published: February 2018

The histone deacetylase inhibitor ITF2357 (givinostat) prevents diastolic dysfunction by enhancing cardiac myofibril relaxation.
WDR5 Facilitates Human Cytomegalovirus Replication by Promoting Capsid Nuclear Egress
Authors: Yang Bo , Liu Xi-Juan , Yao Yongxuan , Jiang Xuan , Wang Xian-Zhang , Yang Hong , Sun Jin-Yan , Miao Yun , Wang Wei , Huang Zhen-Li , Wang Yanyi , Tang Qiyi , Rayner Simon , Britt William J. , McVoy Michael A. , Luo Min-Hua , Zhao Fei
Published: February 2018

WD repeat-containing protein 5 (WDR5) is essential for assembling the VISA-associated complex to induce a type I interferon antiviral response to Sendai virus infection. However, the roles of WDR5 in DNA virus infections are not well described. Here, we report that human cytomegalovirus exploits WDR5 to facilitate capsid nuclear egress. Overexpression of WDR5 in fibroblasts slightly enhanced the infectious virus yield. However, WDR5 knockdown dramatically reduced infectious virus titers with only a small decrease in viral genome replication or gene expression. Further investigation of late steps of viral replication found that WDR5 knockdown significantly impaired formation of the viral nuclear egress complex and induced substantially fewer infoldings of the inner nuclear membrane. In addition, fewer capsids were associated with these infoldings, and there were fewer capsids in the cytoplasm. Restoration of WDR5 partially reversed these effects. These results suggest that WDR5 knockdown impairs the nuclear egress of capsids, which in turn decreases virus titers. These findings reveal an important role for a host factor whose function(s) is usurped by a viral pathogen to promote efficient replication. Thus, WDR5 represents an interesting regulatory mechanism and a potential antiviral target.

IMPORTANCE
Human cytomegalovirus (HCMV) has a large (∼235-kb) genome with over 170 open reading frames and exploits numerous cellular factors to facilitate its replication. HCMV infection increases protein levels of WD repeat-containing protein 5 (WDR5) during infection, overexpression of WDR5 enhances viral replication, and knockdown of WDR5 dramatically attenuates viral replication. Our results indicate that WDR5 promotes the nuclear egress of viral capsids, the depletion of WDR5 resulting in a significant decrease in production of infectious virions. This is the first report that WDR5 favors HCMV, a DNA virus, replication and highlights a novel target for antiviral therapy.
Mobile stroke unit triage of patients with a suspected stroke: a novel solution to reducing suspected stroke admissions in busy emergency departments
Authors: Shuaib Ashfaq , Amlani Shy , Kalashyan Hayrapet , Morrison Laurel , Khan Khurshid , Jickling Glen , Buck Brian , Butcher Kenneth , Saqqur Maher , Jeerakathil Thomas
Published: February 2018

Background

Evaluation of patients with a suspected stroke is one of the most common neurological emergencies requiring rapid, comprehensive assessment by the stroke service to determine patient eligibility for timely reperfusion therapies. Prehospital evaluation may help to improve patient selection and reduce avoidable admissions to overcapacity emergency departments.

Methods and results

We report on our early experience of prehospital triage of patients with a suspected stroke using a mobile stroke unit (MSU) equipped with CT scanner in rural Alberta. During the initial 4 months of operation, 28 patients were evaluated by the team in the MSU. Eight patients were within the time window of thrombolysis and were treated with intravenous tissue plasminogen activator in the MSU. No patients suffered haemorrhage or any other complications. Fourteen patients with multiple aetiologies (stroke mimics 6, transient ischaemic attacks 2, subacute stroke outside thrombolysis window 2, intracranial haemorrhage 3 and cerebral contusion 1) were assessed in the field and transferred to the tertiary hospital. Six patients after assessment and imaging were repatriated back to the local hospital as they were deemed stroke mimics or were outside of the reperfusion window.

Conclusions

The MSU offers a novel approach to performing timely evaluation and treatment of patients with a suspected stroke in rural settings and may help reduce admissions to overcapacity tertiary care facilities.
Protocol for a prospective, school-based standardisation study of a digital social skills assessment tool for children: The Paediatric Evaluation of Emotions, Relationships, and Socialisation (PEERS) study
Authors: Thompson Emma J , Beauchamp Miriam H , Darling Simone J , Hearps Stephen J C , Brown Amy , Charalambous George , Crossley Louise , Darby David , Dooley Julian J , Greenham Mardee , Jaimangal Mohinder , McDonald Skye , Muscara Frank , Turkstra Lyn , Anderson Vicki A
Published: February 2018

Background

Humans are by nature a social species, with much of human experience spent in social interaction. Unsurprisingly, social functioning is crucial to well-being and quality of life across the lifespan. While early intervention for social problems appears promising, our ability to identify the specific impairments underlying their social problems (eg, social communication) is restricted by a dearth of accurate, ecologically valid and comprehensive child-direct assessment tools. Current tools are largely limited to parent and teacher ratings scales, which may identify social dysfunction, but not its underlying cause, or adult-based experimental tools, which lack age-appropriate norms. The present study describes the development and standardisation of Paediatric Evaluation of Emotions, Relationships, and Socialisation(PEERS®), an iPad-based social skills assessment tool.

Methods

The PEERS project is a cross-sectional study involving two groups: (1) a normative group, recruited from early childhood, primary and secondary schools across metropolitan and regional Victoria, Australia; and (2) a clinical group, ascertained from outpatient services at The Royal Children’s Hospital Melbourne (RCH). The project aims to establish normative data for PEERS®, a novel and comprehensive app-delivered child-direct measure of social skills for children and youth. The project involves recruiting and assessing 1000 children aged 4.0–17.11 years. Assessments consist of an intellectual screen, PEERS® subtests, and PEERS-Q, a self-report questionnaire of social skills. Parents and teachers also complete questionnaires relating to participants’ social skills. Main analyses will comprise regression-based continuous norming, factor analysis and psychometric analysis of PEERS® and PEERS-Q.

Ethics and dissemination

Ethics approval has been obtained through the RCH Human Research Ethics Committee (34046), the Victorian Government Department of Education and Early Childhood Development (002318), and Catholic Education Melbourne (2166). Findings will be disseminated through international conferences and peer-reviewed journals. Following standardisation of PEERS®, the tool will be made commercially available.
Major determinant of the occurrence of pacing-induced cardiomyopathy in complete atrioventricular block: a multicentre, retrospective analysis over a 15-year period in South Korea
Authors: Kim Jun Hyung , Kang Ki-Woon , Chin Jung Yeon , Kim Tae-Seok , Park Jae-Hyeong , Choi Yu Jeong
Published: February 2018

Objectives

The predictors of pacing-induced cardiomyopathy (PICM) for complete atrioventricular block (CAVB) have not yet been defined. The aim of this study was to investigate the major determinant of the occurrence of PICM.

Setting

This is a multicentre, retrospective analysis of CAVB from tertiary referral centres in Daejeon, South Korea.

Participants

A cohort of 900 consecutive patients with an implanted pacemaker was collected from December 2001 to August 2015. Of these, a total of 130 patients with CAVB with pacing-dependent rhythm who underwent ECG and echocardiogram before and after implantation were analysed for the occurrence of PICM.

Outcome measures

Cox proportional hazards models evaluated the determinant of PICM by ECG, device parameters and echocardiogram over a mean of 4.5 years.

Results

PICM was observed in 16.1% (n=21) of all patients with CAVB (age, 64±11 years; male, 36.2%). The preimplant left ventricular (LV) ejection fraction (66%±9% vs 66%±8%) and non-apical pacing (40.4% vs 33.3%) were similar; however, the native QRS duration (124±34 ms vs 149±32 ms) and the paced QRS duration (pQRSd) (139±29 ms vs 167±28 ms) were significantly different between the two groups. The postimplant LV ejection fraction (61%±7% vs 31%±8%) was also significantly different at the end of follow-up. A pQRSd significantly correlated with PICM (HR 1.05, 95% CI 1.02 to 1.09, P=0.001). A pQRSd with a cut-off value of above 140 ms had a sensitivity of 95% while a pQRSd with a cut-off value of above 167 ms had a specificity of 90% for PICM.

Conclusion

In patients with CAVB with pacing-dependent rhythm, regardless of the pacing site, the pQRSd is a major determinant of the occurrence of PICM.
Osteochondral defects of the talus with a focus on platelet-rich plasma as a potential treatment option: a review
Authors: Elghawy Ahmed Aly , Sesin Carlos , Rosselli Michael
Published: February 2018

Objective

To provide a review of osteochondral lesions of the talus, to discuss the evidence of the risks and benefits of platelet-rich plasma (PRP) as a viable treatment option, and to measure the efficacy of PRP using MRI evidence of cartilage regeneration, as well as scales that measure improvement in ‘pain’ and ‘functionality’.

Eligibility criteria

Studies that use PRP in either conservative or intraoperative settings to treat osteochondral defects of the talus.

Results

There are seven studies that compare hyaluronic acid or standard surgical options against PRP in treating osteochondral lesions of the talus. Five studies use PRP as supplemental treatment in intraoperative settings, while two studies use PRP conservatively as intra-articular injections. There were minimal adverse effects. Pain and functionality scores consistently improved in those who underwent PRP treatments over the course of 4 years. MRI showed significant but inconsistent results in chondral regeneration.

Conclusion

PRP may show clinical benefit in those with osteochondral lesions of the talus in terms of pain and functionality, although chondral regeneration via MRI is inconsistent. Limitations include the small sample sizes in these seven studies, as well as no standardised formula for PRP preparation.

Clinical relevance

To serve as an overview of the literature regarding PRP treatment for osteochondral lesions of the talus and how this modality may improve patient outcomes in pain, functionality and chondral regeneration. A case is reported to complement the subject review.
Run Clever – No difference in risk of injury when comparing progression in running volume and running intensity in recreational runners: A randomised trial
Authors: Ramskov Daniel , Rasmussen Sten , Sørensen Henrik , Parner Erik Thorlund , Lind Martin , Nielsen Rasmus Oestergaard
Published: February 2018

Background/aim

The Run Clever trial investigated if there was a difference in injury occurrence across two running schedules, focusing on progression in volume of running intensity (Sch-I) or in total running volume (Sch-V). It was hypothesised that 15% more runners with a focus on progression in volume of running intensity would sustain an injury compared with runners with a focus on progression in total running volume.

Methods

Healthy recreational runners were included and randomly allocated to Sch-I or Sch-V. In the first eight weeks of the 24-week follow-up, all participants (n=839) followed the same running schedule (preconditioning). Participants (n=447) not censored during the first eight weeks entered the 16-week training period with a focus on either progression in intensity (Sch-I) or volume (Sch-V). A global positioning system collected all data on running. During running, all participants received real-time, individualised feedback on running intensity and running volume. The primary outcome was running-related injury (RRI).

Results

After preconditioning a total of 80 runners sustained an RRI (Sch-I n=36/Sch-V n=44). The cumulative incidence proportion (CIP) in Sch-V (reference group) were CIP2 weeks4.6%; CIP4 weeks8.2%; CIP8 weeks13.2%; CIP16 weeks28.0%. The risk differences (RD) and 95% CI between the two schedules were RD2 weeks=2.9%(−5.7% to 11.6%); RD4 weeks=1.8%(−9.1% to 12.8%); RD8 weeks=−4.7%(−17.5% to 8.1%); RD16 weeks=−14.0% (−36.9% to 8.9%).

Conclusion

A similar proportion of runners sustained injuries in the two running schedules.
How consistent are associations between maternal and paternal education and child growth and development outcomes across 39 low-income and middle-income countries?
Authors: Jeong Joshua , Kim Rockli , Subramanian S V
Published: February 2018

Background

Maternal and paternal education are associated with improved early child outcomes. However, less is known about how these relative associations compare for preschool children’s growth versus development outcomes; and across country contexts.

Methods

We analysed data from 89 663 children aged 36 to 59 months in 39 low-income and middle-income countries (LMICs). We used linear regression models with country fixed effects to estimate the joint associations between maternal and paternal education and children’s growth and development outcomes. Additionally, we examined the variability in these relationships by each country and within subgroups of countries.

Results

In the pooled sample, maternal and paternal education were independently associated with 0.37 (95% CI 0.33 to 0.41) and 0.20 (95% CI 0.16 to 0.24) higher height-for-age z-scores, and 0.31 (95% CI 0.29 to 0.34) and 0.16 (95% CI 0.14 to 0.18) higher Early Childhood Development Index z-scores, respectively (comparing secondary or higher to no education). Associations were stronger for maternal education than paternal education but comparable between child outcomes. In country-specific regressions, we found the most heterogeneity in the associations between maternal education and children’s growth; and between paternal education and children’s development. Subgroup analyses suggested that these associations may be systematically patterned by country-level adult illiteracy, infant mortality and food insecurity.

Conclusion

Our findings highlight variability in the statistical significance and magnitude of the associations between caregivers’ education and children’s outcomes. Further research is needed to understand the sources of variation that may promote or constrain the benefits of caregivers’ education for children’s early health and development in LMICs.
Combat-related foot injuries: impact on gait and functional outcome
Authors: de Kruijff Loes G M , Prins M , van der Krans A , Hoencamp R , van der Wurff P
Published: February 2018

Introduction

Prior to deployment of the Netherlands Army Task Force Urozgan in Afghanistan, the Dutch Military and civilian healthcare systems had limited experience in treating blast injuries and their long-term consequences. This meant that guidelines for treatment and rehabilitation were lacking. The aim of this cohort study was to quantify kinematic and kinetic abnormalities in service members with foot injuries in relation to functional outcome using gait analysis.

Method

In nine service members with combat-related talus, calcaneus and/or navicular bone (TCN) fractures and nine controls, gait parameters were measured using Gait Real-Time Analysis Interactive Lab system. High-level mobility was evaluated by the Comprehensive High-Level Activity Mobility Predictor (CHAMP), and functional ability was assessed by Lower Extremity Functional Scale (LEFS) questionnaire.

Results

Significant differences were found for LEFS and CHAMP scores (P<0.01), comfortable walking speed and ankle joint range of motion (ROM) (P<0.05), all lower in the group with TCN fractures. For this group, a trend (0.1>P>0.05) for higher step width and lower stride duration and peak power was found. A strong correlation (0.6>r>0.79) is shown between LEFS and comfortable walking speed and CHAMP and ankle joint ROM. The correlations between LEFS and stride duration, step width, ankle joint ROM and peak power, and between CHAMP and comfortable walking speed and stride duration, were moderate (0.4>r>0.59).

Conclusions

This study demonstrated that service members with TCN fractures, compared with healthy controls, have altered gait characteristics, specifically lower walking speed and ankle joint ROM, both related to lower physical functioning. Patients with bilateral depressed Böhler’s angle had the worse functional performance, and further research is recommended to evaluate the relationship between Böhler’s angle and physical performance.

Clinical Trial

The Dutch Ministry of Defence (MOD) and the Institutional Review Board and Medical Ethics Review Committee Brabant, The Netherlands, approved this study (P1550).
The Barrel vascular reconstruction device for endovascular coiling of wide-necked intracranial aneurysms: a multicenter, prospective, post-marketing study
Authors: Gory Benjamin , Blanc Raphaël , Turjman Francis , Berge Jérôme , Piotin Michel
Published: February 2018

Background and purpose

The Barrel vascular reconstruction device (Barrel VRD) is a novel stent with design features that allow endovascular coiling of wide-necked bifurcation aneurysms while preserving adjacent branches, without necessitating dual stent implantation. This study aimed to assess the safety and effectiveness of the Barrel VRD at 12-month follow-up.

Materials and methods

The Barrel VRD trial is a prospective, multicenter, observational post-marketing registry evaluating the use of the Barrel VRD for treatment of wide-necked bifurcation aneurysms. The primary effectiveness endpoint was successful aneurysm treatment measured by digital subtraction angiography with a Raymond–Roy occlusion grade of 1 or 2 in the absence of retreatment, parent artery stenosis (>50%), or target aneurysm rupture at 12 months. The primary safety endpoint was the absence of neurological death or major stroke at 12 months.

Results

Twenty patients were enrolled from December 2013 to December 2014. The device was implanted in 19 patients with 19 aneurysms (8 middle cerebral artery, 4 anterior communicating artery, 1 internal carotid artery terminus, 4 basilar artery aneurysms; mean dome height 5.7±1.91 mm; mean neck length 4.8±1.35 mm, mean dome-to-neck ratio 1.6±2.0). Coiling was performed in all cases. The primary effectiveness endpoint was achieved in 78.9% of subjects (15/19; 12 complete occlusions, 3 neck remnants), and the primary safety endpoint was 5.3% (1/19).

Conclusions

This prospective study demonstrates that the Barrel VRD device resulted in ~80% occlusion rates and ~5% rates of neurological complications at 1 year after endovascular treatment of wide-necked bifurcation intracranial aneurysms.

Registered clinical trial

NCT02125097;Results.