bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between Arterial Stiffness and Skin Microvascular Function: The SUVIMAX2 Study and The Maastricht Study
Authors: van Sloten Thomas T. , Czernichow Sébastien , Houben Alfons J. , Protogerou Athanase D. , Henry Ronald M. , Muris Dennis M. , Schram Miranda T. , Sep Simone J. , Dagnelie Pieter C. , van der Kallen Carla J. , Schaper Nicolaas C. , Blacher Jacques , Hercberg Serge , Levy Bernard I. , Stehouwer Coen D. 
Published: December 2014

BACKGROUND
It has been hypothesized that arterial stiffness leads to generalized microvascular dysfunction and that individuals with type 2 diabetes mellitus (T2DM) are particularly prone to the detrimental effects of arterial stiffness. However, evidence for an association between stiffness and markers of generalized microvascular dysfunction is lacking. We therefore investigated the association between arterial stiffness and skin microvascular function in individuals without and with T2DM.

METHODS
Cross-sectional data were used of The Supplementation en Vitamines et Mineraux Antioxydants 2 (SUVIMAX2) Study (n = 284/62.2 years/48.6% women/0% T2DM (by design)) and The Maastricht Study (n = 737/59.7 years/45.2% women/28.8% T2DM (by design)). Arterial stiffness was determined by carotid-femoral pulse wave velocity (cfPWV). Skin capillaroscopy was used to determine capillary density at baseline, and during reactive hyperemia and venous congestion. Laser Doppler flowmetry was used to assess acetylcholine- and local heating-induced vasoreactivity, and skin flowmotion.

RESULTS
In The SUVIMAX2 Study, cfPWV (per +1 SD) was not associated with baseline capillary density (regression coefficient: −0.48 (95% confidence interval: 2.37; 1.41)) or capillary recruitment during venous congestion (0.54% (−0.74; 1.81%)). In addition, cfPWV was not associated with acetylcholine (−0.02% (−0.14; 0.10%)) or local heating-induced vasoreactivity (0.03% (−0.07; 0.12%)). In The Maastricht Study, in individuals without T2DM, cfPWV was not associated with baseline capillary density (−1.20 (−3.17; 0.77)), and capillary recruitment during reactive hyperemia (1.22% (−0.41; 2.84%)) or venous congestion (1.50% (−0.25; 3.25%)). In addition, cfPWV was not associated with flowmotion (−0.01 (−0.07; 0.06)). Results were adjusted for age and sex. Additional adjustments for confounders did not materially change these results. Results were qualitatively similar in individuals with T2DM.

CONCLUSIONS
Arterial stiffness is not associated with skin microvascular function, irrespective of the presence of T2DM.
Association between oral fluoroquinolone use and the development of retinal detachment: a systematic review and meta-analysis of observational studies
Authors: Chui Celine S. L. , Wong Ian C. K. , Wong Lisa Y. L. , Chan Esther W. 
Published: December 2014

Abstract

Objectives
Several observational studies have been published investigating the association between oral fluoroquinolone use and the development of retinal detachment; however, the findings are not concordant. This study is a meta-analysis of the existing literature and estimates the overall absolute risk of such an event.

Methods
Electronic databases were searched for observational studies on the association between oral fluoroquinolone and retinal detachment up to August 2014. Studies that did not meet the criteria for meta-analysis were narratively reviewed. Cases of retinal detachment during current fluoroquinolone use were also extracted for absolute risk calculation.

Results
Seven observational studies were included. Three (case–control and self-controlled case series studies) were eligible for meta-analysis and four (cohort studies) were narratively reviewed. The rate ratio of the case–control studies was 1.82 (95% CI 0.67–4.93), I2 = 96% and the incidence rate ratio of the self-controlled case series was 1.03 (95% CI 0.84–1.27), I2 = 36%. Three of the four cohort studies found no significant association between oral fluoroquinolone use and the development of retinal detachment. The pooled absolute risk of retinal detachment whilst on current oral fluoroquinolone treatment is estimated to be 4.85 per 1 000 000 prescriptions (95% CI 0.78–8.91).

Conclusions
The findings of this systematic review and meta-analysis do not support an association between oral fluoroquinolone use and the development of retinal detachment. Given the low absolute risk, such an event would be rare if there were an association. The current prescribing practice for fluoroquinolones should not be altered because of a previously suggested potential risk of retinal detachment.
Isolation of B subunit‐specific monoclonal antibody clones that strongly neutralize the toxicity of Shiga toxin 2
Authors: Arimitsu Hideyuki , Sasaki Keiko , Iba Yoshitaka , Kurosawa Yoshikazu , Shimizu Toshiyasu , Tsuji Takao 
Published: December 2014

ABSTRACTShiga toxin 2 (Stx2)‐specific mAb‐producing hybridoma clones were generated from mice. Because mice tend to produce small amounts of B subunit (Stx2B)‐specific antibodies at the polyclonal antibody level after immunization via the parenteral route, mice were immunized intranasally with Stx2 toxoids with a mutant heat‐labile enterotoxin as a mucosal adjuvant; 11 different hybridoma clones were obtained in two trials. Six of them were A subunit (Stx2A)‐specific whereas five were Stx2B‐specific antibody‐producing clones. The in vitro neutralization activity of Stx2B‐specific mAbs against Stx2 was greater than that of Stx2A‐specific mAbs on HeLa229 cells. Furthermore, even at low concentrations two of the Stx2B‐specific mAbs (45 and 75D9) completely inhibited receptor binding and showed in vivo neutralization activity against a fivefold median lethal dose of Stx2 in mice. In western blot analysis, these Stx2B‐specific neutralization antibodies did not react to three different mutant forms of Stx2, each amino acid residue of which was associated with receptor binding. Additionally, the nucleotide sequences of the VH and VL regions of clones 45 and 75D9 were determined. Our Stx2B‐specific mAbs may be new candidates for the development of mouse‐human chimeric Stx2‐neutralizing antibodies which have fewer adverse effects than animal antibodies for enterohemorrhagic Escherichia coli infection.
In situ DNA‐hybridization chain reaction (HCR): a facilitated in situ HCR system for the detection of environmental microorganisms
Authors: Yamaguchi Tsuyoshi , Kawakami Shuji , Hatamoto Masashi , Imachi Hiroyuki , Takahashi Masanobu , Araki Nobuo , Yamaguchi Takashi , Kubota Kengo 
Published: December 2014

SummaryIn situ detection of microorganisms by fluorescence in situ hybridization (FISH) is a powerful tool for environmental microbiology, but analyses can be hampered by low rRNA content in target organisms, especially in oligotrophic environments. Here, we present a non‐enzymatic, hybridization chain reaction (HCR)‐based signal amplified in situ whole‐cell detection technique (in situ DNA‐HCR). The components of the amplification buffer were optimized to polymerize DNA amplifier probes for in situ DNA‐HCR. In situ hybridization of initiator probes followed by signal amplification via HCR produced bright signals with high specificity and probe permeation into cells. The detection rates for Bacteria in a seawater sample and Archaea in anaerobic sludge samples were comparable with or greater than those obtained by catalyzed reporter deposition (CARD)‐FISH or standard FISH. Detection of multiple organisms (Bacteria, Archaea and Methanosaetaceae) in an anaerobic sludge sample was achieved by simultaneous in situ DNA‐HCR. In summary, in situ DNA‐HCR is a simple and easy technique for detecting single microbial cells and enhancing understanding of the ecology and behaviour of environmental microorganisms in situ.
Inside ‘bed management’: ethnographic insights from the vantage point of UK hospital nurses
Authors: Allen Davina 
Published: December 2014

AbstractIn the face of unprecedented financial and demographic challenges, optimising acute bed utilisation by the proactive management of patient flows is a pressing policy concern in high‐income countries. Despite the growing literature on this topic, bed management has received scant sociological attention. Drawing on practice‐based approaches, this article deploys ethnographic data to examine bed management from the perspective of UK hospital nurses. While the nursing contribution to bed management is recognised formally in their widespread employment in patient access and discharge liaison roles, nurses at all levels in the study site were enrolled in this organisational priority. Rather than the rational, centrally controlled processes promulgated by policymakers, bed management emerges as a predominantly distributed activity, described here as match‐making. An example of micro‐level rationing, for the most part, match‐making was not informed by explicit criteria nor did it hinge on clearly identifiable decisions to grant or deny access. Rather it was embedded in the everyday practices and situated rationalities through which nurses accomplished the accommodations necessary to balance demand with resources.
One species in eight: DNA barcodes from type specimens resolve a taxonomic quagmire
Authors: Mutanen Marko , Kekkonen Mari , Prosser Sean W. J. , Hebert Paul D. N. , Kaila Lauri 
Published: December 2014

AbstractEach holotype specimen provides the only objective link to a particular Linnean binomen. Sequence information from them is increasingly valuable due to the growing usage of DNA barcodes in taxonomy. As type specimens are often old, it may only be possible to recover fragmentary sequence information from them. We tested the efficacy of short sequences from type specimens in the resolution of a challenging taxonomic puzzle: the Elachista dispunctella complex which includes 64 described species with minuscule morphological differences. We applied a multistep procedure to resolve the taxonomy of this species complex. First, we sequenced a large number of newly collected specimens and as many holotypes as possible. Second, we used all >400 bp examine species boundaries. We employed three unsupervised methods (BIN, ABGD, GMYC) with specified criteria on how to handle discordant results and examined diagnostic bases from each delineated putative species (operational taxonomic units, OTUs). Third, we evaluated the morphological characters of each OTU. Finally, we associated short barcodes from types with the delineated OTUs. In this step, we employed various supervised methods, including distance‐based, tree‐based and character‐based. We recovered 658 bp barcode sequences from 194 of 215 fresh specimens and recovered an average of 141 bp from 33 of 42 holotypes. We observed strong congruence among all methods and good correspondence with morphology. We demonstrate potential pitfalls with tree‐, distance‐ and character‐based approaches when associating sequences of varied length. Our results suggest that sequences as short as 56 bp can often provide valuable taxonomic information. The results support significant taxonomic oversplitting of species in the Elachista dispunctella complex.
Epistasis and the sensitivity of phenotypic screens for beta thalassaemia
Authors: Penman Bridget S. , Gupta Sunetra , Weatherall David J. 
Published: December 2014

SummaryGenetic disorders of haemoglobin, particularly the sickle cell diseases and the alpha and beta thalassaemias, are the commonest inherited disorders worldwide. The majority of affected births occur in low‐income and lower‐middle income countries. Screening programmes are a vital tool to counter these haemoglobinopathies by: (i) identifying individual carriers and allowing them to make informed reproductive choices, and (ii) generating population level gene‐frequency estimates, to help ensure the optimal allocation of public health resources. For both of these functions it is vital that the screen performed is suitably sensitive. One popular first‐stage screening option to detect carriers of beta thalassaemia in low‐income countries is the One Tube Osmotic Fragility Test (OTOFT). Here we introduce a population genetic framework within which to quantify the likely sensitivity and specificity of the OTOFT in different epidemiological contexts. We demonstrate that interactions between the carrier states for beta thalassaemia and alpha thalassaemia, glucose‐6‐phosphate dehydrogenase deficiency and Southeast Asian Ovalocytosis have the potential to reduce the sensitivity of OTOFTs for beta thalassaemia heterozygosity to below 70%. Our results therefore caution against the widespread application of OTOFTs in regions where these erythrocyte variants co‐occur.
Superficial vein thrombosis: a current approach to management
Authors: Scott Gemma , Mahdi Ali Jassem , Alikhan Raza 
Published: December 2014

SummarySuperficial vein thrombosis (SVT) was considered to be a benign and self‐limiting condition. However, it is now appreciated that a significant proportion of those presenting with SVT will have concomitant deep vein thrombosis or pulmonary embolism, or are at significant risk of developing deep venous thromboembolism. Potential therapeutic options include topical preparations, compression therapy (stockings, bandages), medication such as non‐steroidal anti‐inflammatory drugs (NSAIDs) or anticoagulants (therapeutic or prophylactic doses) and surgery, ligation or stripping, of superficial veins. The treatment of choice is therapeutic/intermediate dose low molecular weight heparin or prophylactic dose fondaparinux administered for 4–6 weeks. The cost‐effectiveness of treatment is a concern and more targeted therapy is required.
Combined cord blood and bone marrow transplantation from the same human leucocyte antigen‐identical sibling donor for children with malignant and non‐malignant diseases
Authors: Tucunduva Luciana , Volt Fernanda , Cunha Renato , Locatelli Franco , Zecca Marco , Yesilipek Akif , Caniglia Maurizio , Güngör Tayfun , Aksoylar Serap , Fagioli Franca , Bertrand Yves , Addari Maria Carmen , de la Fuente Josu , Winiarski Jacek , Biondi Andrea , Sengeloev Henrik , Badell Isabel , Mellgren Karin , de Heredia Cristina Díaz , Sedlacek Petr , Vora Ajay , Rocha Vanderson , Ruggeri Annalisa , Gluckman Eliane ,   Eurocord and the EBMT Paediatric working party
Published: December 2014

SummaryUmbilical cord blood (UCB) from an human leucocyte antigen (HLA)‐identical sibling can be used for transplantation of patients with malignant and non‐malignant diseases. However, the low cellular content of mostUCBunits represents a limitation to this approach. An option to increase cell dose is to harvest bone marrow (BM) cells from the same donor and infuse them along with theUCB. We studied 156 children who received such a combined graft between 1992 and 2011. Median age was 7 years and 78% of patients (n = 122) were transplanted for non‐malignant diseases, mainly haemoglobinopathies. Acute leukaemia (n = 26) was the most frequent malignant diagnosis. Most patients (91%) received myeloablative conditioning. Median donor age was 1·7 years, median infused nucleated cell dose was 24·4 × 107/kg and median follow‐up was 41 months. Sixty‐days neutrophil recovery occurred in 96% of patients at a median of 17 d. The probabilities of grade‐II‐IVacute and chronic graft‐versus‐host disease (GVHD) were 19% and 10%, respectively. Four‐year overall survival was 90% (68% malignant; 97% non‐malignant diseases) with 3% probability of death. In conclusion, combinedUCBandBMtransplantation from anHLA‐identical sibling donor is an effective treatment for children with malignant and non‐malignant disorders with high overall survival and low incidence ofGVHD.
Lack of bone lesions at diagnosis is associated with inferior outcome in multisystem langerhans cell histiocytosis of childhood
Authors: Aricò Maurizio , Astigarraga Itziar , Braier Jorge , Donadieu Jean , Gadner Helmut , Glogova Evgenia , Grois Nicole , Henter Jan‐Inge , Janka Gritta , McClain Kenneth L. , Ladisch Stephan , Pötschger Ulrike , Rosso Diego , Thiem Elfriede , Weitzman Sheila , Windebank Kevin , Minkov Milen ,   the Histiocyte Society
Published: December 2014

SummarySkeletal involvement is generally, but not universally, characteristic of Langerhans cell histiocytosis (LCH). We investigated whether the presence of bone lesions at diagnosis is a prognostic factor for survival inLCH. Nine hundred and thirty‐eight children with multisystem (MS)LCH, both high (386RO+) and low (RO−) risk, were evaluated for bone lesions at diagnosis. Risk organ (RO+) involvement was defined as: haematopoietic system (haemoglobin <100 g/l, and/or white blood cell count <4·0 × 109/l and/or platelet count <100 × 109/l), spleen (>2 cm below the costal margin), liver (>3 cm and/or hypoproteinaemia, hypoalbuminaemia, hyperbilirubinaemia, and/or increased aspartate transaminase/alanine transaminase). Given the general view that prognosis inLCHworsens with increasing extent of disease, the surprising finding was that inMS+RO+LCHthe probability of survival with bone involvement 74 ± 3% (n = 230, 56 events) was reduced to 62 ± 4% (n = 156, 55 events) if this was absent (P = 0·007). An even greater difference was seen in the subgroup of patients with both liver and either haematopoiesis or spleen involvement: 61 ± 5% survival (n = 105; 52 events) if patients had bony lesions,versus47 ± 5% (n = 111; 39 events) if they did not (P = 0·014). This difference was retained in multivariate analysis (P = 0·048). Although as yet unexplained, we conclude that bone involvement at diagnosis is a previously unrecognized favourable prognostic factor inMS+RO+LCH.
Selective activation of angiotensin AT2 receptors attenuates progression of pulmonary hypertension and inhibits cardiopulmonary fibrosis
Authors: Bruce E , Shenoy V , Rathinasabapathy A , Espejo A , Horowitz A , Oswalt A , Francis J , Nair A , Unger T , Raizada M K , Steckelings U M , Sumners C , Katovich M J 
Published: December 2014

Background and PurposePulmonary hypertension (PH) is a devastating disease characterized by increased pulmonary arterial pressure, which progressively leads to right‐heart failure and death. A dys‐regulated renin angiotensin system (RAS) has been implicated in the development and progression of PH. However, the role of the angiotensin AT2 receptor in PH has not been fully elucidated. We have taken advantage of a recently identified non‐peptide AT2 receptor agonist, Compound 21 (C21), to investigate its effects on the well‐established monocrotaline (MCT) rat model of PH.Experimental ApproachA single s.c. injection of MCT (50 mg·kg−1) was used to induce PH in 8‐week‐old male Sprague Dawley rats. After 2 weeks of MCT administration, a subset of animals began receiving either 0.03 mg·kg−1 C21, 3 mg·kg−1 PD‐123319 or 0.5 mg·kg−1 A779 for an additional 2 weeks, after which right ventricular haemodynamic parameters were measured and tissues were collected for gene expression and histological analyses.Key ResultsInitiation of C21 treatment significantly attenuated much of the pathophysiology associated with MCT‐induced PH. Most notably, C21 reversed pulmonary fibrosis and prevented right ventricular fibrosis. These beneficial effects were associated with improvement in right heart function, decreased pulmonary vessel wall thickness, reduced pro‐inflammatory cytokines and favourable modulation of the lung RAS. Conversely, co‐administration of the AT2 receptor antagonist, PD‐123319, or the Mas antagonist, A779, abolished the protective actions of C21.Conclusions and ImplicationsTaken together, our results suggest that the AT2 receptor agonist, C21, may hold promise for patients with PH.
A6V polymorphism of the human μ‐opioid receptor decreases signalling of morphine and endogenous opioids in vitro
Authors: Knapman Alisa , Santiago Marina , Connor Mark 
Published: December 2014

Background and PurposePolymorphisms of the μ opioid receptor (MOPr) may contribute to the variation in responses to opioid drugs in clinical and unregulated situations. The A6V variant of MOPr (MOPr‐A6V) is present in up to 20% of individuals in some populations, and may be associated with heightened susceptibility to drug abuse. There are no functional studies examining the acute signalling of MOPr‐A6V in vitro, so we investigated potential functional differences between MOPr and MOPr‐A6V at several signalling pathways using structurally distinct opioid ligands.Experimental ApproachCHO and AtT‐20 cells stably expressing MOPr and MOPr‐A6V were used. AC inhibition and ERK1/2 phosphorylation were assayed in CHO cells; K channel activation was assayed in AtT‐20 cells.Key ResultsBuprenorphine did not inhibit AC or stimulate ERK1/2 phosphorylation in CHO cells expressing MOPr‐A6V, but buprenorphine activation of K channels in AtT‐20 cells was preserved. [D‐Ala2, N‐MePhe4, Gly‐ol]‐enkephalin, morphine and β‐endorphin inhibition of AC was significantly reduced via MOPr‐A6V, as was signalling of all opioids to ERK1/2. However, there was little effect of the A6V variant on K channel activation.Conclusions and ImplicationsSignalling to AC and ERK via the mutant MOPr‐A6V was decreased for many opioids, including the clinically significant drugs morphine, buprenorphine and fentanyl, as well endogenous opioids. The MOPr‐A6V variant is common and this compromised signalling may affect individual responses to opioid therapy, while the possible disruption of the endogenous opioid system may contribute to susceptibility to substance abuse.
Zoogeography of theSanAndreasFault system:GreatPacificFractureZones correspond with spatially concordant phylogeographic boundaries in westernNorthAmerica
Authors: Gottscho Andrew D. 
Published: December 2014

ABSTRACTThe purpose of this article is to provide an ultimate tectonic explanation for several well‐studied zoogeographic boundaries along the west coast ofNorthAmerica, specifically, along the boundary of theNorthAmerican andPacific plates (theSanAndreasFault system). By reviewing 177 references from the plate tectonics and zoogeography literature,Idemonstrate that fourGreatPacificFractureZones (GPFZs) in thePacific plate correspond with distributional limits and spatially concordant phylogeographic breaks for a wide variety of marine and terrestrial animals, including invertebrates, fish, amphibians, reptiles, birds, and mammals. These boundaries are: (1)CapeMendocino and theNorthCoastDivide, (2)PointConception and theTransverseRanges, (3)PuntaEugenia and theVizcaínoDesert, and (4)CaboCorrientes and theSierraTransvolcanica. However, discussion of theGPFZsis mostly absent from the zoogeography and phylogeography literature likely due to a disconnect between biologists and geologists. I argue that the four zoogeographic boundaries reviewed here ultimately originatedviathe same geological process (triple junction evolution). Finally, I suggest how a comparative phylogeographic approach can be used to test the hypothesis presented here.