bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome analysis of predator‐ and prey‐induced phenotypic plasticity in the Hokkaido salamander (Hynobius retardatus)
Authors: Matsunami Masatoshi , Kitano Jun , Kishida Osamu , Michimae Hirofumi , Miura Toru , Nishimura Kinya
Published: May 2015

Predator‐ and prey‐induced phenotypic plasticity is widely observed among amphibian species. Although ecological factors inducing diverse phenotypic responses have been extensively characterized, we know little about the molecular bases of variation in phenotypic plasticity. Larvae of the Hokkaido salamander, Hynobius retardatus, exhibit two distinct morphs: the presence of their prey, Rana pirica tadpoles, induces a broad‐headed attack morph, and the presence of predatory dragonfly nymphs (Aeshna nigroflava) induces a defence morph with enlarged external gills and a high tail. To compare the genes involved in predator‐ and prey‐induced phenotypic plasticity, we carried out a de novo transcriptome analysis of Hokkaido salamander larvae exposed to either prey or predator individuals. First, we found that the number of genes involved in the expression of the defence morph was approximately five times the number involved in the expression of the attack morph. This result is consistent with the fact that the predator‐induced plasticity involves more drastic morphological changes than the prey‐induced plasticity. Second, we found that particular sets of genes were upregulated during the induction of both the attack and defence morphs, but others were specific to the expression of one or the other morph. Because both shared and unique molecular mechanisms were used in the expression of each morph, the evolution of a new plastic phenotype might involve both the co‐option of pre‐existing molecular mechanisms and the acquisition of novel regulatory mechanisms.
Diagnostic, prognostic and predictive relevance of molecular markers in gliomas
Authors: Brandner Sebastian , von Deimling Andreas
Published: May 2015

The advances of genome‐wide ‘discovery platforms’ and the increasing affordability of the analysis of significant sample sizes have led to the identification of novel mutations in brain tumours that became diagnostically and prognostically relevant. The development of mutation‐specific antibodies has facilitated the introduction of these convenient biomarkers into most neuropathology laboratories and has changed our approach to brain tumour diagnostics. However, tissue diagnosis will remain an essential first step for the correct stratification for subsequent molecular tests, and the combined interpretation of the molecular and tissue diagnosis ideally remains with the neuropathologist. This overview will help our understanding of the pathobiology of common intrinsic brain tumours in adults and help guiding which molecular tests can supplement and refine the tissue diagnosis of the most common adult intrinsic brain tumours. This article will discuss the relevance of 1p/19q codeletions, IDH1/2 mutations, BRAF V600E and BRAF fusion mutations, more recently discovered mutations in ATRX, H3F3A, TERT, CIC and FUBP1, for diagnosis, prognostication and predictive testing. In a tumour‐specific topic, the role of mitogen‐activated protein kinase pathway mutations in the pathogenesis of pilocytic astrocytomas will be covered.
Neutrophil gelatinase‐associated lipocalin attenuates injury in the rat cecal ligation and puncture model of sepsis via apoptosis inhibition
Authors: Zhao Shuangping , Wei Yangjing , Xu Daomiao
Published: May 2015

Aim

The aim of this study was to investigate the effect of neutrophil gelatinase‐associated lipocalin (NGAL) on the rat cecal ligation and puncture (CLP)‐induced sepsis and the possible mechanism.

Methods

Thirty male Sprague–Dawley rats underwent CLP as sepsis models and were randomized into three groups including the sham‐operated group (sham, n = 10), which only underwent a laparotomy; the sepsis group (sepsis, n = 10), which underwent CLP and subcutaneous injection of normal saline; and the sepsis + NGAL group (sepsis + NGAL, n = 10), which underwent CLP and subcutaneous injection of NGAL. Urine, blood and kidney tissue samples were collected for the determination of urine NGAL (uNGAL), plasma NGAL (pNGAL), serum creatinine (Scr), blood urea nitrogen (BUN), histomorphological and immunohistochemical examination, lipid peroxidation product malondialdehyde (MDA) and superoxide dismutase (SOD), and expression of heme oxygenase‐1 (HO)‐1.

Results

The levels of uNGAL, pNGAL, Scr, BUN, kidney injury score, positive TUNEL staining, activated Caspase‐3 and Bax, and kidney tissue MDA levels in the sepsis group were significantly increased compared with those in the sham‐operated group and the sepsis + NGAL group (P < 0.05). SOD level and HO‐1 expression in sepsis + NGAL group were significantly higher than those in the sham‐operated group and the sepsis group (P < 0.05).

Conclusion

NGAL can attenuate kidney injury and apoptosis in the rat CLP model of sepsis. And the protective effect of NGAL was probably due to the inhibition of apoptosis and lipid peroxidation, and increased expression of HO‐1.
Anorectal dysfunction in patients with ulcerative colitis: impaired adaptation or enhanced perception?
Authors: Brochard C. , Siproudhis L. , Ropert A. , Mallak A. , Bretagne J‐F , Bouguen G.
Published: May 2015

Background

Rectal disorders during ulcerative colitis (UC) drastically alter the quality of life and may result from an impairment of rectal perception and compliance. This study aims to assess anorectal disorders in patients with mild‐to‐moderate UC.

Methods

Anal pressures and the rectal responses to phasic rectal isobaric distension in 10 patients with mild‐to‐moderate UC were prospectively compared with those in 10 healthy volunteers (HVs).

Key Results

The patients in each group were similar regarding age, gender, and delivery. In the resting state, the anal canal pressures were similar between the groups. Only the squeeze pressures of the lower anal canal were significantly lower in UC patients than in HVs. During phasic isobaric distension, rectal sensitivity was similar between the groups, whatever the step of distension. Isobaric rectal distension resulted in a significant decrease of the rectoanal inhibitory reflex and a decrease in rectal tone and a significant drop in rectal compliance in UC patients compared with HVs.

Conclusions & Inferences

Patients showing mild‐to‐moderate UC experience rectal compliance and innervation disorders without a significant change in rectal sensitivity. The findings of this work suggest impairment not only of the properties of the rectal wall but also of intrinsic innervation. Repeated evaluation over time may be helpful for analyzing the reversibility of the process after healing.
Food safety considerations for innovative nutrition solutions
Authors: Byrd‐Bredbenner Carol , Cohn Marjorie Nolan , Farber Jeffrey M. , Harris Linda J. , Roberts Tanya , Salin Victoria , Singh Manpreet , Jaferi Azra , Sperber William H.
Published: May 2015

Failure to secure safe and affordable food to the growing global population leads far too often to disastrous consequences. Among specialists and other individuals, food scientists have a key responsibility to improve and use science‐based tools to address risk and advise food handlers and manufacturers with best‐practice recommendations. With collaboration from production agriculture, food processors, state and federal agencies, and consumers, it is critical to implement science‐based strategies that address food safety and that have been evaluated for effectiveness in controlling and/or eliminating hazards. It is an open question whether future food safety concerns will shift in priority given the imperatives to supply sufficient food. This report brings together leading food safety experts to address these issues with a focus on three areas: economic, social, and policy aspects of food safety; production and postharvest technology for safe food; and innovative public communication for food safety and nutrition.
Neuroimmune and neuroendocrine abnormalities in depression: two sides of the same coin
Authors: Horowitz Mark A. , Zunszain Patricia A.
Published: May 2015

Major depressive disorder has been linked to alterations in several interacting systems, particularly with respect to neuroendocrine and neuroinflammatory dysfunction. Increased levels of both cortisol and proinflammatory cytokines have regularly been described. This presents an apparent paradox, given the well‐known anti‐inflammatory properties of glucocorticoids, including inhibition of cytokine release. There are two competing theories to resolve this paradox: one proposes that reduced glucocorticoid signaling, as a result of glucocorticoid resistance, creates a permissive environment for an overactive innate immune system; the other theory focuses on evidence that glucocorticoids can be proinflammatory under some circumstances, depending on context and temporal factors. This review assesses the evidence base and limitations of both theories, discussing animal and clinical data, and preliminary work in human neural cells. Further work to delineate the relationship between neuroimmune and neuroendocrine systems in depression will be critical for understanding the biological perturbations underpinning depression, and therefore, for discerning treatment targets, and we include suggestions for future directions.
E‐selectin expression induced by Porphyromonas gingivalis in human endothelial cells via nucleotide‐binding oligomerization domain‐like receptors and Toll‐like receptors
Authors: Wan M. , Liu J.R. , Wu D. , Chi X.P. , Ouyang X.Y.
Published: May 2015

Porphyromonas gingivalis, an important periodontal pathogen, has been proved to actively invade cells, induce endothelial cell activation, and promote development of atherosclerosis. Innate immune surveillance, which includes the activity of nucleotide‐binding oligomerization domain (NOD)‐like receptors (NLRs) and Toll‐like receptors (TLRs), are essential for the control of microbial infections; however, the roles of receptor families in P. gingivalis infections remain unclear. Here, we examined the roles of NLRs and TLRs in endothelial cell activation caused by P. gingivalis. Live P. gingivalis and whole cell sonicates were used to stimulate endothelial cells, and both showed upregulation of E‐selectin as well as NOD1, NOD2, and TLR2. In addition, silencing of these genes in endothelial cells infected with P. gingivalis led to a reduction in E‐selectin expression. Porphyromonas gingivalis also induced nuclear factor‐κB (NF‐κB) and P38 mitogen‐activated protein kinase (MAPK) activity in endothelial cells, whereas small interfering RNA targeting NOD1 significantly reduced these signals. Moreover, inhibition of either NOD2 or TLR2 inhibited NF‐κB significantly, but had only a weak inhibitory effect on P38 MAPK signaling. Direct inhibition of NF‐κB and P38 MAPK significantly attenuated E‐selectin expression induced by P. gingivalis in endothelial cells. Taken together, these findings suggest that NOD1, NOD2, and TLR2 play important, non‐redundant roles in endothelial cell activation following P. gingivalis infection.
The TaDREB3 transgene transferred by conventional crossings to different genetic backgrounds of bread wheat improves drought tolerance
Authors: Shavrukov Yuri , Baho Manahil , Lopato Sergiy , Langridge Peter
Published: May 2015

Drought tolerance of the wheat cultivar Bobwhite was previously enhanced by transformation with a construct containing the wheat DREB3 gene driven by the stress‐inducible maize Rab17 promoter. Progeny of a single T2 transgenic line were used as pollinators in crosses with four elite bread wheat cultivars from Western Australia: Bonnie Rock, IGW‐2971, Magenta and Wyalkatchem, with the aim of evaluating transgene performance in different genetic backgrounds. The selected pollinator line, BW8‐9‐10‐3, contained multiple transgene copies, had significantly improved drought tolerance compared with wild‐type plants and showed no growth and development penalties or abnormalities. A single hybrid plant was selected from each cross‐combination for three rounds of backcrossing with the corresponding maternal wheat cultivar. The transgene was detected in all four F1BC3 combinations, but stress‐inducible transgene expression was found in only three of the four combinations. Under well‐watered conditions, the phenotypes and grain yield components of the F2BC3 transgene‐expressing lines were similar to those of corresponding recurrent parents and null‐segregants. Under severe drought conditions, the backcross lines demonstrated 12–18% higher survival rates than the corresponding control plants. Two from four F3BC3 transgenic lines showed significantly higher yield (18.9% and 21.5%) than control plants under limited water conditions. There was no induction of transgene expression under cold stress, and therefore, no improvement of frost tolerance observed in the progenies of drought‐tolerant F3BC3 lines.
Seasonal and within‐canopy variation in shoot‐scale resource‐use efficiency trade‐offs in a Norway spruce stand
Authors: Tarvainen Lasse , Räntfors Mats , Wallin Göran
Published: May 2015

Previous leaf‐scale studies of carbon assimilation describe short‐term resource‐use efficiency (RUE) trade‐offs where high use efficiency of one resource requires low RUE of another. However, varying resource availabilities may cause long‐term RUE trade‐offs to differ from the short‐term patterns. This may have important implications for understanding canopy‐scale resource use and allocation. We used continuous gas exchange measurements collected at five levels within a Norway spruce, Picea abies (L.) karst., canopy over 3 years to assess seasonal differences in the interactions between shoot‐scale resource availability (light, water and nitrogen), net photosynthesis (An) and the use efficiencies of light (LUE), water (WUE) and nitrogen (NUE) for carbon assimilation. The continuous data set was used to develop and evaluate multiple regression models for predicting monthly shoot‐scale An. These models showed that shoot‐scale An was strongly dependent on light availability and was generally well described with simple one‐ or two‐parameter models. WUE peaked in spring, NUE in summer and LUE in autumn. However, the relative importance of LUE for carbon assimilation increased with canopy depth at all times. Our results suggest that accounting for seasonal and within‐canopy trade‐offs may be important for RUE‐based modelling of canopy carbon uptake.
Using Sociograms to Enhance Power and Voice in Focus Groups
Authors: Baiardi Janet M. , Gultekin Laura , Brush Barbara L.
Published: May 2015

Objective

To discuss the use of sociograms in our focus groups with homeless sheltered mothers and to assess facilitator influence and the distribution of power influence.

Design and Sample

An exploratory, descriptive qualitative design that utilizes both focus groups and sociograms. Two focus groups were conducted in December 2009 (N = 7) and January 2010 (N = 4). Data analysis included a content analysis and a process analysis using sociograms to graphically represent group participant dynamics.

Results

Use of the sociogram provided a means to assess the influence of the facilitator as well as quantify the degree to which group participants' voices are included.

Conclusion

Using sociograms provides a viable mechanism to complement content analysis and increase the methodological rigor of focus groups in health care research.
Characterization and taxonomic reassessment of the box blight pathogen Calonectria pseudonaviculata, introducing Calonectria henricotiae sp. nov.
Authors: Gehesquière B. , Crouch J. A. , Marra R. E. , Van Poucke K. , Rys F. , Maes M. , Gobin B. , Höfte M. , Heungens K.
Published: May 2015

Calonectria pseudonaviculata, the causal agent of the disease of Buxus spp. known as ‘box blight’, was first detected in the mid‐1990s in the UK and New Zealand. Since then, the geographic range of box blight has rapidly expanded to at least 21 countries throughout temperate regions of the world, causing significant losses in nurseries, gardens and wild boxwood populations. This study determined the genetic diversity in a collection of 234 Calonectria isolates from diseased Buxus plants, originating from 15 countries and four continents. Two genetic clades, G1 and G2, were identified within this sample using multilocus phylogenetic analysis. The application of genealogical concordance phylogenetic species recognition criteria using four independent nuclear loci determined that the Calonectria isolates in these two clades are separate phylogenetic species. The isolates in the G1 clade were upheld as C. pseudonaviculata sensu stricto. Based on phylogenetic distinctiveness and the lack of mating, a new species is proposed, Calonectria henricotiae sp. nov., for the Calonectria isolates in the G2 clade. A PCR‐RFLP assay and real‐time PCR assays were developed to easily and reproducibly differentiate these species. To assess the practical implications of the identification of the two species, their physiology, fungicide susceptibility and pathogenicity were compared. No differences in pathogenicity were observed. However, C. henricotiae isolates exhibited greater thermotolerance and reduced sensitivity to specific triazole as well as strobilurin fungicides. The identification of a second phylogenetic species causing box blight may have a substantial impact on the epidemiology and control of this destructive disease.
Assessing the Impact of a Research‐Based STEM Program on STEM Majors' Attitudes and Beliefs
Authors: Huziak‐Clark Tracy , Sondergeld Toni , van Staaden Moira , Knaggs Christine , Bullerjahn Anne
Published: May 2015

The Science, Engineering, and Technology Gateway of Ohio (SETGO) program has a three‐pronged approach to meeting the needs at different levels of students in the science, technology, engineering, and mathematics (STEM) pipeline. The SETGO program was an extensive collaboration between a two‐year community college and a nearby four‐year institution. Two of these approaches, the STEM Summer Research Program and Owens Ready Bridge, have been found to be effective in significantly increasing participants' beliefs and attitudes for both males and females. Participants cite integrative learning activities, mentoring, and small group interactions as some reasons for their growth. This study utilized a mixed‐method approach to better understand the reasons for participant and program success. After five years of evaluation of the SETGO program, findings suggest that students feel more confident not only in their preparation for the rigors of a STEM degree, but also in their decisions to complete the degree.
Identifying Key Components of Teaching and Learning in a STEM School
Authors: Morrison Judith , Roth McDuffie Amy , French Brian
Published: May 2015

This study was conducted at an innovative science, technology, engineering, and mathematics high school, providing a rich contextual description of the teaching and learning at the school, specifically focusing on problem solving and inquiry approaches, and students' motivation, social interactions, and collaborative work. Data were collected through interviews with teachers and students, classroom observations, school meetings, school design and planning efforts, student surveys, and student standardized test scores. We saw that the teaching and learning at the school were typically inquiry and problem based and that student motivation, collaboration, and social interactions were strong due to the environment of inquiry and problem‐based teaching and learning.
Water and sediment transport mechanisms in a large river‐connected lake
Authors: Wang Hua , Zhang Zhizhang , Song Depeng , Zhou Yiyi , Liu Xiaodong
Published: May 2015

Using the finite volume method, a 2‐D water‐sediment coupled model was developed to investigate the transport mechanisms of water and sediment in Poyang Lake, the largest river‐connected lake in China. Simulating water and sediment transport processes in an average water year revealed that the total volume of water and the amount of suspended sediment transported from the five main rivers upstream of Poyang Lake were approximately 1.56 × 1011 m3 and 1.25 × 107 t, respectively. The outputs of water and sediment from the lake to the downstream Yangtze River were approximately 2.17 × 1011 m3 and 1.53 × 107 t, respectively. During the wet season, especially between July and September, nearly 1.06 × 1010 m3 of water and 1.89 × 106 t of suspended sediment were transported upstream from the Yangtze River into the lake due to the high external water levels, which accounted for 4.88% and 12.35%, respectively, of the total annual transport from the lake into the Yangtze River.
Noise properties of CT images reconstructed by use of constrained total‐variation, data‐discrepancy minimization
Authors: Rose Sean , Andersen Martin S. , Sidky Emil Y. , Pan Xiaochuan
Published: May 2015

Purpose:

The authors develop and investigate iterative image reconstruction algorithms based on data‐discrepancy minimization with a total‐variation (TV) constraint. The various algorithms are derived with different data‐discrepancy measures reflecting the maximum likelihood (ML) principle. Simulations demonstrate the iterative algorithms and the resulting image statistical properties for low‐dose CT data acquired with sparse projection view angle sampling. Of particular interest is to quantify improvement of image statistical properties by use of the ML data fidelity term.

Methods:

An incremental algorithm framework is developed for this purpose. The instances of the incremental algorithms are derived for solving optimization problems including a data fidelity objective function combined with a constraint on the image TV. For the data fidelity term the authors, compare application of the maximum likelihood principle, in the form of weighted least‐squares (WLSQ) and Poisson‐likelihood (PL), with the use of unweighted least‐squares (LSQ).

Results:

The incremental algorithms are applied to projection data generated by a simulation modeling the breast computed tomography (bCT) imaging application. The only source of data inconsistency in the bCT projections is due to noise, and a Poisson distribution is assumed for the transmitted x‐ray photon intensity. In the simulations involving the incremental algorithms an ensemble of images, reconstructed from 1000 noise realizations of the x‐ray transmission data, is used to estimate the image statistical properties. The WLSQ and PL incremental algorithms are seen to reduce image variance as compared to that of LSQ without sacrificing image bias. The difference is also seen at few iterations—short of numerical convergence of the corresponding optimization problems.

Conclusions:

The proposed incremental algorithms prove effective and efficient for iterative image reconstruction in low‐dose CT applications particularly with sparse‐view projection data.
Variability in CT lung‐nodule volumetry: Effects of dose reduction and reconstruction methods
Authors: Young Stefano , Kim Hyun J. Grace , Ko Moe Moe , Ko War War , Flores Carlos , McNitt‐Gray Michael F.
Published: May 2015

Purpose:

Measuring the size of nodules on chest CT is important for lung cancer staging and measuring therapy response. 3D volumetry has been proposed as a more robust alternative to 1D and 2D sizing methods. There have also been substantial advances in methods to reduce radiation dose in CT. The purpose of this work was to investigate the effect of dose reduction and reconstruction methods on variability in 3D lung‐nodule volumetry.

Methods:

Reduced‐dose CT scans were simulated by applying a noise‐addition tool to the raw (sinogram) data from clinically indicated patient scans acquired on a multidetector‐row CT scanner (Definition Flash, Siemens Healthcare). Scans were simulated at 25%, 10%, and 3% of the dose of their clinical protocol (CTDIvol of 20.9 mGy), corresponding to CTDIvol values of 5.2, 2.1, and 0.6 mGy. Simulated reduced‐dose data were reconstructed with both conventional filtered backprojection (B45 kernel) and iterative reconstruction methods (SAFIRE: I44 strength 3 and I50 strength 3). Three lab technologist readers contoured “measurable” nodules in 33 patients under each of the different acquisition/reconstruction conditions in a blinded study design. Of the 33 measurable nodules, 17 were used to estimate repeatability with their clinical reference protocol, as well as interdose and inter‐reconstruction‐method reproducibilities. The authors compared the resulting distributions of proportional differences across dose and reconstruction methods by analyzing their means, standard deviations (SDs), and t‐test and F‐test results.

Results:

The clinical‐dose repeatability experiment yielded a mean proportional difference of 1.1% and SD of 5.5%. The interdose reproducibility experiments gave mean differences ranging from −5.6% to −1.7% and SDs ranging from 6.3% to 9.9%. The inter‐reconstruction‐method reproducibility experiments gave mean differences of 2.0% (I44 strength 3) and −0.3% (I50 strength 3), and SDs were identical at 7.3%. For the subset of repeatability cases, inter‐reconstruction‐method mean/SD pairs were (1.4%, 6.3%) and (−0.7%, 7.2%) for I44 strength 3 and I50 strength 3, respectively. Analysis of representative nodules confirmed that reader variability appeared unaffected by dose or reconstruction method.

Conclusions:

Lung‐nodule volumetry was extremely robust to the radiation‐dose level, down to the minimum scanner‐supported dose settings. In addition, volumetry was robust to the reconstruction methods used in this study, which included both conventional filtered backprojection and iterative methods.
Learning Goals and the Challenge Course Experience: An Exploratory Study
Authors: Schary David P. , Lewis Alexis B. , Cardinal Bradley J.
Published: May 2015

This study explored the short- and long-term ability of a university affiliated challenge course program to provide a lasting, quality experience for college participants aligning with the university's Learning Goals for Graduates (LGGs). The Challenge Course Experience Questionnaire (CCEQ), a newly created assessment tool, was administered to 375 participants in 16 different groups. Participants completed a four to six hour program, consisting of low- and high-course elements. Participants were assessed before, immediately after, and three months following their program. A significant increase in both CCEQ variables and LGGs immediately following the challenge course program was observed; however, a three-month follow-up revealed the majority of measured concepts had significantly decreased below or back to initial levels. These findings have implications for practitioners in terms of perceived challenge course benefits and long-term learning outcome retention. Suggestions for challenge course professionals and future research considerations are given.
An Examination of Campus Recreation Usage, Academic Performance, and Selected Health Indices of College Freshmen
Authors: Brock Magen , Carr Julie Wallace , Todd Mikel Kent
Published: May 2015

Cross-sectional research shows that campus recreation (CR) facility use is related to higher grade point averages (GPA) and favorable health indices. Further research is needed to address whether the relationships are caused by greater use of CR facilities or the accommodation of existing behaviors valued by students with higher GPA and favorable health indices. Thus, 179 first year student's GPA, body mass index (BMI), television (TV) viewing, physical activity (IPAQ), and nutrient intakes were compared between those who increased CR visits (by ≥ 1 day/wk), and those who decreased CR visits (by ≥ 1 day/wk) between fall and spring semesters. No significant ( p < .05) differences were found between the groups for GPA, BMI, TV time, IPAQ scores, or nutrient intakes. Though these data indicate that GPA and health indices are minimally impacted by an increase or decrease in CR use, they suggest that students with higher GPA and favorable health indices are more likely to use CR facilities.
When Recreation is More than Just Sport: Advancing the Leadership Development of Students in Intramurals and Club Sports
Authors: Dugan John P. , Turman Natasha T. , Torrez Mark Anthony
Published: May 2015

Student levels of participation in intramurals and club sports exceed those of other forms of co-curricular involvement. This positions collegiate recreation as a powerful context for student learning. This study uses a multi-institutional dataset with representation from 29,811 participants in intramurals and club sports to examine influences on leadership development. Findings offer insights on how best to leverage students' leadership capacity, leadership efficacy, social perspective-taking, and resilience.
Actin cytoskeletal remodeling with protrusion formation is essential for heart regeneration in Hippo-deficient mice
Authors: Morikawa Yuka , Zhang Min , Heallen Todd , Leach John , Tao Ge , Xiao Yang , Bai Yan , Li Wei , Willerson James T. , Martin James F.
Published: May 2015

Inhibiting the Hippo pathway could promote heart regeneration by encouraging heart cells to move into injured areas.
Feedback circuitry between
miR-218
repression and RTK activation in glioblastoma
Authors: Mathew Lijoy K. , Huangyang Peiwei , Mucaj Vera , Lee Samuel S. , Skuli Nicolas , Eisinger-Mathason T.S. Karin , Biju Kevin , Li Bo , Venneti Sriram , Lal Priti , Lathia Justin D. , Rich Jeremy N. , Keith Brian , Simon M. Celeste
Published: May 2015

Oncogenic feedback loops explain how loss of a microRNA enhances proliferative signaling in glioblastoma.
Environmental Isolates of Azole-Resistant Aspergillus fumigatus in Germany
Authors: Bader Oliver , Tünnermann Jana , Dudakova Anna , Tangwattanachuleeporn Marut , Weig Michael , Groß Uwe
Published: May 2015

Azole antifungal drug resistance in
Aspergillus fumigatus
is an emerging problem in several parts of the world. Here we investigated the distribution of such strains in soils from Germany. At a general positivity rate of 12%, most prevalently, we found strains with the TR
34
/L98H and TR
46
/Y121F/T289A alleles, dispersed along a corridor across northern Germany. Comparison of the distributions of resistance alleles and genotypes between environment and clinical samples suggests the presence of local clinical clusters.
A Mutation of RNA Polymerase β′ Subunit (RpoC) Converts Heterogeneously Vancomycin-Intermediate Staphylococcus aureus (hVISA) into “Slow VISA”
Authors: Matsuo Miki , Hishinuma Tomomi , Katayama Yuki , Hiramatsu Keiichi
Published: May 2015

Various mutations in the
rpoB
gene, which encodes the RNA polymerase β subunit, are associated with increased vancomycin (VAN) resistance in vancomycin-intermediate
Staphylococcus aureus
(VISA) and heterogeneously VISA (hVISA) strains. We reported that
rpoB
mutations are also linked to the expression of the recently found “slow VISA” (sVISA) phenotype (M. Saito, Y. Katayama, T. Hishinuma, A. Iwamoto, Y. Aiba, K Kuwahara-Arai, L. Cui, M. Matsuo, N. Aritaka, and K. Hiramatsu, Antimicrob Agents Chemother 58:5024–5035, 2014,
http://dx.doi.org/10.1128/AAC.02470-13
). Because RpoC and RpoB are components of RNA polymerase, we examined the effect of the
rpoC
(P440L) mutation on the expression of the sVISA phenotype in the Mu3
fdh2
*V6-5 strain (V6-5), which was derived from a previously reported hVISA strain with the VISA phenotype. V6-5 had an extremely prolonged doubling time (DT) (72 min) and high vancomycin MIC (16 mg/liter). However, the phenotype of V6-5 was unstable, and the strain frequently reverted to hVISA with concomitant loss of low growth rate, cell wall thickness, and reduced autolysis. Whole-genome sequencing of phenotypic revertant strain V6-5-L1 and comparison with V6-5 revealed a second mutation, F562L, in
rpoC
. Introduction of the wild-type (WT)
rpoC
gene using a multicopy plasmid resolved the sVISA phenotype of V6-5, indicating that the
rpoC
(P440L) mutant expressed the sVISA phenotype in hVISA. To investigate the mechanisms of resistance in the sVISA strain, we independently isolated an additional 10 revertants to hVISA and VISA. In subsequent whole-genome analysis, we identified compensatory mutations in the genes of three distinct functional categories: the
rpoC
gene itself as regulatory mutations, peptidoglycan biosynthesis genes, and
relQ
, which is involved in the stringent response. It appears that the
rpoC
(P440L) mutation causes the sVISA phenotype by augmenting cell wall peptidoglycan synthesis and through the control of the stringent response.
Determination of MIC Distribution and Epidemiological Cutoff Values for Bedaquiline and Delamanid in Mycobacterium tuberculosis Using the MGIT 960 System Equipped with TB eXiST
Authors: Keller Peter M. , Hömke Rico , Ritter Claudia , Valsesia Giorgia , Bloemberg Guido V. , Böttger Erik C.
Published: May 2015

Bedaquiline (Sirturo) and delamanid (Deltyba) have recently been approved by the regulatory authorities for treatment of multidrug-resistant tuberculosis (MDR-TB). Antimicrobial susceptibility testing is not established for either substance. On the basis of the use of the MGIT 960 system equipped with EpiCenter/TB eXiST, we determined a mean bedaquiline MIC for wild-type strains of 0.65 mg/liter (median, 0.4 mg/liter) and an epidemiological cutoff (ECOFF) of 1.6 mg/liter; for delamanid, a mean wild-type drug MIC of 0.013 mg/liter (median, 0.01 mg/liter) and an ECOFF of 0.04 mg/liter were determined.
Outbreak of NDM-1-Producing Klebsiella pneumoniae Causing Neonatal Infection in a Teaching Hospital in Mainland China
Authors: Zhang XiaoYu , Li XianPing , Wang Min , Yue HeJia , Li PengLing , Liu YaPing , Cao Wei , Yao DongMei , Liu Li , Zhou XiaoLan , Zheng Rong , Bo Tao
Published: May 2015

The emergence and spread of bacteria carrying the
bla
NDM-1
gene has become a worldwide concern. Here, we report eight cases of
Klebsiella pneumoniae
with
bla
NDM-1
in the neonatal ward of a teaching hospital in mainland China. Multilocus sequence typing showed that seven isolates were clonally related and confirmed them as sequence type 17 (ST17). One isolate belonged to ST433. These findings suggest continuous spread of
bla
NDM-1
in mainland China and emphasize the need for intensive surveillance and precautions.
Rationale, secondary outcome scores and 1-year follow-up of a randomised trial of platelet-rich plasma injections in acute hamstring muscle injury: the Dutch Hamstring Injection Therapy study
Authors: Reurink Gustaaf , Goudswaard Gert Jan , Moen Maarten H , Weir Adam , Verhaar Jan A N , Bierma-Zeinstra Sita M A , Maas Mario , Tol Johannes L
Published: May 2015

Background

Platelet-rich plasma (PRP) injections are an experimental treatment for acute muscle injuries. We examined whether PRP injections would accelerate return to play after hamstring injury. The methods and the primary outcome measure were published in theNew England Journal of Medicine(NEJM) as ‘Platelet-rich plasma injections in acute muscle injury’ (2014). This article shares information not available in theNEJMletter or online supplement, especially the rationale behind the study and the secondary outcome measures including 1 year re-injury data.

Methods

We performed a multicentre, randomised, double-blind, placebo-controlled trial in 80 competitive and recreational athletes with acute hamstring muscle injuries. Details can be found in theNEJM(http://www.nejm.org/doi/full/10.1056/NEJMc1402340). The primary outcome measure was the time needed to return to play during 6 months of follow-up. Not previously reported secondary outcome scores included re-injury at 1 year, alteration in clinical and MRI parameters, subjective patient satisfaction and the hamstring outcome score.

Results

In the earlierNEJMpublication, we reported that PRP did not accelerate return to play; nor did we find a difference in the 2-month re-injury rate. We report no significant between-group difference in the 1-year re-injury rate (HR=0.89; 95% CI, 0.38 to 2.13; p=0.80) or any other secondary outcome measure.

Conclusions

At 1-year postinjection, we found no benefit of intramuscular PRP compared with placebo injections in patients with acute hamstring injuries in the time to return to play, re-injury rate and alterations of subjective, clinical or MRI measures.
Sex differences in the association of fasting and postchallenge glucose levels with grip strength among older adults: the Rancho Bernardo Study
Authors: Kalyani Rita Rastogi , Kim Catherine , Ferrucci Luigi , Laughlin Gail A , Kritz-Silverstein Donna , Kong Shengchun , Nan Bin , Barrett-Connor Elizabeth
Published: May 2015

Objective

Persons with diabetes have accelerated muscle loss. The association of fasting and postchallenge glucose levels per se to grip strength, a clinical marker of poor physical function, and potential sex differences in this relationship has not been previously described.

Design

Longitudinal cohort.

Setting

USA.

Participants

Participants were community-dwelling older adults (mean age 71.3 years) without self-reported diabetes and/or use of diabetes medication with glucose measured at baseline (1992–1996).

Measurements

Fasting plasma glucose (FPG) was measured in 1019 women and 636 men. Two-hour glucose (2HG) levels after a 75 g oral glucose tolerance test were also available (women, n=870; men, n=559). Dominant hand grip strength was assessed using a hand-held dynamometer at 3.0±1.6 visits over a median 7.0 years. Mixed linear models examined the association of baseline glucose levels with grip strength, accounting for repeated visits, and adjusting for covariates.

Results

Sex-specific FPG quartiles were associated with unadjusted differences in grip strength among women (p=0.03) but not men (p=0.50). However, in men, adjusting for age, education, height, weight, peripheral neuropathy, physical activity, and comorbidities, each SD (SD=17 mg/dL) higher FPG was associated with persistently lower grip strength (−0.44±0.22 kg, p=0.049); 2HG (SD=50 mg/dL) was unrelated to grip strength (−0.39±0.25 kg, p=0.13). In women, neither FPG (SD=16 mg/dL) nor 2HG (SD=45 mg/dL) was associated with grip strength (0.02±0.12 kg, p=0.90; and −0.20±0.14 kg, p=0.14; respectively) after adjustment. The rate of change in grip strength did not differ across FPG or 2HG quartiles in either sex.

Conclusions

In age-adjusted analyses, elevated fasting glucose levels are associated with persistently lower grip strength in older men, but not women. Future studies are needed to elucidate reasons for these sex differences and may provide further insight into accelerated loss of muscle function as a complication of diabetes in older adults.
Exposure to air pollution and meteorological factors associated with children’s primary care visits at night due to asthma attack: case-crossover design for 3-year pooled patients
Authors: Yamazaki Shin , Shima Masayuki , Yoda Yoshiko , Oka Katsumi , Kurosaka Fumitake , Shimizu Shigeta , Takahashi Hironobu , Nakatani Yuji , Nishikawa Jittoku , Fujiwara Katsuhiko , Mizumori Yasuyuki , Mogami Akira , Yamada Taku , Yamamoto Nobuharu
Published: May 2015

Objective

We examined the association of outdoor air pollution and meteorological parameters with primary care visits (PCVs) at night due to asthma attack.

Setting

A case-crossover study was conducted in a primary care clinic in Himeji City, Japan.

Participants

Participants were 1447 children aged 0–14 years who visited the clinic with an asthma attack from April 2010 until March 2013.

Exposure

Daily concentrations of air pollutants and meteorological parameters were measured.

Primary outcome

PCVs at night due to asthma attack. A conditional logistic regression model was used to estimate ORs of PCVs per unit increment of air pollutants or meteorological parameters (the per-unit increments of particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) and ozone were 10 μg/m3and 10 ppb, respectively). Analyses took into consideration the effects of seasonality.

Results

We noted an association between PCVs and daily ozone levels on the day before a PCV (OR=1.17; 95% CI 1.01 to 1.35; p=0.04), as well as between PCVs and 3-day mean ozone levels before a PCV (OR=1.29; 95% CI 1.00 to 1.46; p=0.04), from April until June. We also observed an association between PCVs and daily PM2.5levels on the day before a PCV from December until March (OR=1.16; 95% CI 1.01 to 1.33; p=0.05). Meteorological parameters, such as hours of sunshine from September until November, atmospheric pressure from April until June, and temperature from April until August, were also found to be associated with PCVs.

Conclusions

The findings in the present study supported an association between ozone and PCVs and suggest that certain meteorological items may be associated with PCVs.
Health gains and financial risk protection: an extended cost-effectiveness analysis of treatment and prevention of diarrhoea in Ethiopia
Authors: Pecenka Clinton J , Johansson Kjell Arne , Memirie Solomon Tessema , Jamison Dean T , Verguet Stéphane
Published: May 2015

Objectives

Policymakers face many decisions when considering public financing for health, including the kind of health interventions to include in a publically financed package. The consequences of these choices will influence health outcomes as well as the financial risk protection provided to different segments of the population. The purpose of this study is to illustrate the size and distribution of benefits due to treatment and prevention of diarrhoea (ie, rotavirus vaccination).

Methods

We use an economic model to examine the impacts of universal public finance (UPF) of diarrhoeal treatment alone, as opposed to diarrhoeal treatment along with rotavirus vaccination in Ethiopia using extended cost-effectiveness analysis (ECEA). ECEA allows us to measure the health gains and financial risk protection provided by these interventions for each wealth quintile. Our model compares a baseline situation with diarrhoeal treatment seeking of 32% (overall) and no rotavirus vaccination, to a situation where UPF increases treatment seeking by 20 percentage points for each quintile and rotavirus vaccination reaches DTP (diphteria, pertussis, tetanus) 2 levels for each quintile (overall rate of 52%). We calculate deaths averted, private expenditures averted and costs incurred by the government under the baseline situation and with UPF.

Results

We find that diarrhoeal treatment paired with rotavirus vaccination is more cost effective than diarrhoeal treatment alone for the metrics we examine in this paper (deaths and private expenditures averted). Per US$1 million invested, diarrhoeal treatment saves 44 lives and averts US$115 000 in private expenditures. For the same investment, diarrhoeal treatment and rotavirus vaccination save 61 lives and avert US$150 000 in private expenditures. The health benefits of these interventions tend to benefit the poor, while the financial benefits favour the better-off.

Conclusions

Policymakers should consider multiple benefit streams as well as their scale and incidence when considering public finance of health interventions.
Managing work–family conflict in the medical profession: working conditions and individual resources as related factors
Authors: Mache Stefanie , Bernburg Monika , Vitzthum Karin , Groneberg David A , Klapp Burghard F , Danzer Gerhard
Published: May 2015

Objectives

This study developed and tested a research model that examined the effects of working conditions and individual resources on work–family conflict (WFC) using data collected from physicians working at German clinics.

Material and methods

This is a cross-sectional study of 727 physicians working in German hospitals. The work environment, WFC and individual resources were measured by the Copenhagen Psychosocial Questionnaire, the WFC Scale, the Brief Resilient Coping Scale and the Questionnaire for Self-efficacy, Optimism and Pessimism. Descriptive, correlation and linear regression analyses were applied.

Results

Clinical doctors working in German hospitals perceived high levels of WFC (mean=76). Sociodemographic differences were found for age, marital status and presence of children with regard to WFC. No significant gender differences were found. WFCs were positively related to high workloads and quantitative job demands. Job resources (eg, influence at work, social support) and personal resources (eg, resilient coping behaviour and self-efficacy) were negatively associated with physicians’ WFCs. Interaction terms suggest that job and personal resources buffer the effects of job demands on WFC.

Conclusions

In this study, WFC was prevalent among German clinicians. Factors of work organisation as well as factors of interpersonal relations at work were identified as significant predictors for WFC. Our results give a strong indication that both individual and organisational factors are related to WFC. Results may play an important role in optimising clinical care. Practical implications for physicians’ career planning and recommendations for future research are discussed.
Does drinking water influence hospital-admitted sialolithiasis on an epidemiological level in Denmark?
Authors: Schrøder Stine , Homøe Preben , Wagner Niels , Vataire Anne-Lise , Lundager Madsen Hans Erik , Bardow Allan
Published: May 2015

Objectives

Sialolithiasis, or salivary stones, is not a rare disease of the major salivary glands. However, the aetiology and incidence remain largely unknown. Since sialoliths are comprised mainly of calcium phosphate salts, we hypothesise that drinking water calcium levels and other elements in drinking water could play a role in sialolithiasis. Owing to substantial intermunicipality differences in drinking water composition, Denmark constitutes a unique environment for testing such relations.

Design

An epidemiological study based on patient data extracted from the National Patient Registry and drinking water data from the Geological Survey of Denmark and Greenland retrieved as weighted data on all major drinking water constituents for each of the 3364 waterworks in Denmark.

All patient cases with International Statistical Classification of Diseases 10th Revision (ICD-10) codes for sialolithiasis registered between the years 2000 and 2010 were included in the study (n=3014) and related to the drinking water composition on a municipality level (n=98).

Primary and secondary outcome measures

Multiple regression analysis using iterative search and testing among all demographic and drinking water variables with sialolithiasis incidence as the outcome in search of possible relations among the variables tested.

Results

The nationwide incidence of hospital-admitted sialolithiasis was 5.5 cases per 100 000 citizens per year in Denmark. Strong relations were found between the incidence of sialolithiasis and the drinking water concentration of calcium, magnesium and hydrogen carbonate, however, in separate models (p<0.001). Analyses also confirmed correlations between drinking water calcium and magnesium and their concentration in saliva whereas this was not the case for hydrogen carbonate.

Conclusions

Differences in drinking water calcium and magnesium may play a role in the incidence of sialolithiasis. These findings are of interest because many countries have started large-scale desalination programmes of drinking water.