bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Utility of Pediatric Isolator Blood Culture System for Detection of Fungemia in Children: a 10-Year Review
Authors: Campigotto Aaron , Richardson Susan E. , Sebert Michael , McElvania TeKippe Erin , Chakravarty Aparna , Doern Christopher D.
Published: June 2016

The use of the Wampole Isolator 1.5-ml pediatric blood culture tube for the detection of fungemia in children was assessed by a 10-year retrospective review at two pediatric hospitals, The Hospital for Sick Children in Toronto, Canada, and the Children's Medical Center of Dallas, Texas. Over this period, a total of 9,442 pediatric Isolator specimens were processed, with yeast or yeast-like organisms recovered in 297 (3.1%) of the specimens (151 [1.6%] unique clinical episodes) and filamentous or dimorphic fungi recovered in 31 (0.3%) of the specimens (25 unique clinical episodes). Only 18 of the 151 clinical episodes of fungemia attributable to yeast were not detected by automated blood culture systems. The majority of isolated yeast wereCandidaspp., which were usually detected by automated systems, whereas the most common non-Candidayeast wasMalassezia furfur, which the automated system failed to detect. Filamentous or dimorphic fungi were detected in 25 episodes, of which only 9 (36%) episodes were deemed clinically significant after chart review, indicating that in the majority of cases (16/25, 64%) fungal isolation represented contamination. In five of the nine clinically significant episodes, the isolated fungus (Histoplasma capsulatum,Coccidioides immitis/posadasii,Fusarium oxysporum,Aspergillusspp., andBipolarisspp.) was also identified in other clinical specimens. Over the 10-year study period, the use of the pediatric Isolator system, at the discretion of the treating physician, only rarely provided useful clinical information for the diagnosis of fungemia in children, with the exception ofM. furfurand possibly endemic mycoses.
Methicillin-Resistant Staphylococcus aureus Control in the 21st Century: Laboratory Involvement Affecting Disease Impact and Economic Benefit from Large Population Studies
Authors: Peterson Lance R. , Schora Donna M.
Published: June 2016

Methicillin-resistant
Staphylococcus aureus
(MRSA) infection is a global health care problem. Large studies (e.g., >25,000 patients) show that active surveillance testing (AST) followed by contact precautions for positive patients is an effective approach for MRSA disease control. With this approach, the clinical laboratory will be asked to select what AST method(s) to use and to provide data monitoring outcomes of the infection prevention interventions. This minireview summarizes evidence for MRSA disease control, reviews the involvement of the laboratory, and provides examples of how to undertake a program cost analysis. Health care organizations with total MRSA clinical infections of >0.3/1,000 patient days or bloodstream infections of >0.03/1,000 patient days should implement a MRSA control plan.
Mitochondrial p53 Contributes to Reovirus-Induced Neuronal Apoptosis and Central Nervous System Injury in a Mouse Model of Viral Encephalitis
Authors: Zhuang Yonghua , Berens-Norman Heather M. , Leser J. Smith , Clarke Penny , Tyler Kenneth L.
Published: June 2016

The tumor suppressor p53 plays a critical part in determining cell fate both as a regulator of the transcription of several proapoptotic genes and through its binding interactions with Bcl-2 family proteins at mitochondria. We now demonstrate that p53 protein levels are increased in infected brains during reovirus encephalitis. This increase occurs in the cytoplasm of reovirus-infected neurons and is associated with the activation of caspase 3. Increased levels of p53 in reovirus-infected brains are not associated with increased expression levels of p53 mRNA, suggesting that p53 regulation occurs at the protein level. Increased levels of p53 are also not associated with the increased expression levels of p53-regulated, proapoptotic genes. In contrast, upregulated p53 accumulates in mitochondria. Previous reports demonstrated that the binding of p53 to Bak at mitochondria causes Bak activation and results in apoptosis. We now show that Bak is activated and that activated Bak is bound to p53 during reovirus encephalitis. In addition, survival is enhanced in reovirus-infected Bak
−/−
mice compared to controls, demonstrating a role for Bak in reovirus pathogenesis. Inhibition of the mitochondrial translocation of p53 with pifithrin μ prevents the formation of p53/Bak complexes following reovirus infection of
ex vivo
brain slice cultures and results in decreased apoptosis and tissue injury. These results suggest that the mitochondrial localization of p53 regulates reovirus-induced pathogenesis in the central nervous system (CNS) through its interactions with Bak.

IMPORTANCE
There are virtually no specific treatments of proven efficacy for virus-induced neuroinvasive diseases. A better understanding of the pathogenesis of virus-induced CNS injury is crucial for the rational development of novel therapies. Our studies demonstrate that p53 is activated in the brain following reovirus infection and may provide a therapeutic target for virus-induced CNS disease.
Comparison of the Gene Coding Contents and Other Unusual Features of the GC-Rich and AT-Rich Branch Probosciviruses
Authors: Ling Paul D. , Long Simon Y. , Zong Jian-Chao , Heaggans Sarah Y. , Qin Xiang , Hayward Gary S.
Published: June 2016

Multiple species of herpesviruses from three different lineages of the
Proboscivirus
genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect either Asian or African elephants, but the highly lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. In the accompanying paper [P. D. Ling et al., mSphere 1(3):e00081-15,
http://dx.doi.org/10.1128/mSphere.00081-15
], we report the complete 206-kb genome of EEHV4, the third different species causing disease in Asian elephants and the first example of a GC-rich branch proboscivirus. To gain insights into the nature and differential properties of these two very anciently diverged lineages of elephant herpesviruses, we describe here several additional unusual features found in the complete GC-rich genome of EEHV4 with particular emphasis on patterns of divergence as well as common unique features that are distinct from those of all other herpesviruses, such as the enlarged AT-rich intergenic domains and gene families, including the large number of vGPCR-like proteins.
Rapid variation in upper-mantle rheology across the San Andreas fault system and Salton Trough, southernmost California, USA
Authors: Barak Shahar , Klemperer Simon L.
Published: June 2016

We present new shear-wave splitting data showing systematic lateral variations in upper-mantle anisotropy across the plate boundary in southernmost California (USA). Beneath the Peninsular Ranges batholith, fast polarization directions parallel the direction of former Farallon subduction, suggestive of a slab remnant. Near the eastern edge of the batholith, across the Elsinore fault, fast polarization directions change rapidly to align with the direction of San Andreas fault shear. We infer that the Elsinore fault penetrates the entire lithosphere and may represent a future localization of the plate boundary that is migrating west from the San Andreas fault. Beneath the Salton Trough and the Chocolate Mountains region, large splitting times, despite a very thin lithosphere, imply vertical melt pockets in the uppermost mantle aligned in the shear direction. Largest splitting times, ∼1.2 s, are seen closest to the Sand Hills fault that projects southeast from the San Andreas fault. Further east, in the southern Basin and Range province, fast directions align with North America absolute plate motion.
Seismicity and sedimentation rate effects on submarine slope stability
Authors: ten Brink U.S. , Andrews B.D. , Miller N.C.
Published: June 2016

We explore the effects of earthquake frequency and sedimentation rate on submarine slope stability by extracting correlations between morphological and geological parameters in 10 continental margins. Slope stability increases with increasing frequency of earthquakes and decreasing sedimentation rate. This increase in stability is nonlinear (power law with b < 0.5), accelerating with decreasing interseismic sediment accumulation. The correlation is interpreted as evidence for sediment densification and associated shear strength gain induced by repeated seismic shaking. Outliers to this correlation likely identify margins where tectonic activity leads to relatively rapid oversteepening of the slope.
Identifying and exploring factors influencing career choice, recruitment and retention of anaesthesia trainees in the UK
Authors: Moore J N , McDiarmid A J , Johnston P W , Cleland J A
Published: June 2016

Background

Many acute hospital specialties are experiencing low recruitment and high attrition of trainees. Understanding what is important to current trainees is critical in terms of identifying and addressing factors which adversely affect recruitment and retention.

Objectives

To identify and explore factors involved in anaesthetic trainees’ career decision making.

Methods

This was a mixed methods study using a questionnaire survey (assessing how influential 18 different factors were when choosing anaesthetics, using a five-point Likert scale), supplemented by semi-structured interviews, carried out in August–December 2014, in Scotland, UK.

Results

42/68 (62%) completed responses were received, representing over half of all core (58%) and Acute Care Common Stem (65%) trainees across Scotland. Overall, questionnaire data indicated that the following were most important in career decision making: perceived job satisfaction among those already in the specialty, structured training, the nature of the work (practical, varied, immediate outcomes). Thirteen interviews were carried out. These highlighted that prior positive exposure and experience with anaesthetists encouraged trainees into the specialty. Enthusiastic, supportive colleagues and structured training (including clear milestones, regular teaching and feedback) were considered to enhance the quality of training. Sustainable working conditions, flexibility within programme and out-of-programme opportunities were valued. Respondents reported concerns about the impact of increasing service delivery demands on training quality.

Conclusions

Many of the elements important to today’s anaesthetics trainees are related to positive learning and working environments. This fits with research findings from other professional groups. These findings can inform the development of programmes which cultivate trainee commitment to, and enthusiasm for, anaesthetics.
Systematic review of the relationships between sleep duration and health indicators in school-aged children and youth
Authors: Chaput Jean-Philippe , Gray Casey E. , Poitras Veronica J. , Carson Valerie , Gruber Reut , Olds Timothy , Weiss Shelly K. , Connor Gorber Sarah , Kho Michelle E. , Sampson Margaret , Belanger Kevin , Eryuzlu Sheniz , Callender Laura , Tremblay Mark S.
Published: June 2016

The objective of this systematic review was to examine the relationships between objectively and subjectively measured sleep duration and various health indicators in children and youth aged 5–17 years. Online databases were searched in January 2015 with no date or study design limits. Included studies were peer-reviewed and met the a priori-determined population (apparently healthy children and youth aged 5–17 years), intervention/exposure/comparator (various sleep durations), and outcome (adiposity, emotional regulation, cognition/academic achievement, quality of life/well-being, harms/injuries, and cardiometabolic biomarkers) criteria. Because of high levels of heterogeneity across studies, narrative syntheses were employed. A total of 141 articles (110 unique samples), including 592 215 unique participants from 40 different countries, met inclusion criteria. Overall, longer sleep duration was associated with lower adiposity indicators, better emotional regulation, better academic achievement, and better quality of life/well-being. The evidence was mixed and/or limited for the association between sleep duration and cognition, harms/injuries, and cardiometabolic biomarkers. The quality of evidence ranged from very low to high across study designs and health indicators. In conclusion, we confirmed previous investigations showing that shorter sleep duration is associated with adverse physical and mental health outcomes. However, the available evidence relies heavily on cross-sectional studies using self-reported sleep. To better inform contemporary sleep recommendations, there is a need for sleep restriction/extension interventions that examine the changes in different outcome measures against various amounts of objectively measured sleep to have a better sense of dose–response relationships.
The Canadian 24-Hour Movement Guidelines for Children and Youth: Implications for practitioners, professionals, and organizations
Authors: Latimer-Cheung Amy E. , Copeland Jennifer L. , Fowles Jonathon , Zehr Lori , Duggan Mary , Tremblay Mark S.
Published: June 2016

The new Canadian 24-Hour Movement Guidelines for Children and Youth emphasize the integration of all movement behaviours that occur over a whole day (i.e., light, moderate, and vigorous physical activity, sedentary behaviour, and sleep). These guidelines shift the paradigm away from considering each behaviour in isolation. This concept of the “whole day matters” not only calls for a change in thinking about movement but also for redevelopment of dissemination and implementation practice. Past guideline launch activities largely have aimed to create awareness through passive dissemination strategies (e.g., Website posts, distribution of print resources). For the integrated guidelines to have public health impact, we must move beyond dissemination and raising of awareness to implementation and behaviour change. Shifting this focus requires new, innovative approaches to intervention, including interdisciplinary collaboration, policy change, and refocused service provision. The purpose of this paper is to identify practitioners, professionals, and organizations with potential to disseminate and/or implement the guidelines, discuss possible implementation strategies for each of these groups, and describe the few resources being developed and those needed to support dissemination and implementation efforts. This discussion makes readily apparent the need for a well-funded, comprehensive, long-term dissemination, implementation, and evaluation plan to ensure uptake and activation of the guidelines.
Reproductive ecology of the distylous species Houstonia longifolia: implications for conservation of a rare species
Authors: Pedersen Jennine L.M. , Macdonald S. Ellen , Nielsen Scott E.
Published: June 2016

Distylous species typically experience self-incompatibility with one morph often having partial self-compatibility. Small populations may therefore experience greater rates of selfing/intramorph crosses leading to skewed morph ratios and reduced seed production. For the distylous species Houstonia longifolia Gaertn. (“imperiled” at its northwestern range limit in Alberta), we examined whether small populations were morph-biased and whether seed production was affected by population size, local density, plant size, morph type, and surrounding morph ratio. For focal plants in several populations, we measured size (height, number of stems) and local density (1 m2) of pins and thrums, with the focal plants collected for seed counts. Population size was estimated from densities in systematically located quadrats in each population. Morph ratios were pin-biased in small populations but were even to slightly thrum-biased in large populations. The critical population size for maintaining an equal morph ratio was ∼726 plants. Seed production was most influenced by the interaction between morph type and surrounding morph ratio, which were themselves influenced by population size (Allee effect). Seed production increased for thrums but decreased for pins as the proportion of surrounding pins increased, suggesting strong incompatibility. These results provide guidance on population size and morph ratios for conservation actions.
A new solution of embedding class I representing anisotropic fluid sphere in general relativity
Authors: Singh Ksh. Newton , Bhar Piyali , Pant Neeraj
Published: June 2016

In this paper, we are willing to develop a model of an anisotropic star by choosing a new [Formula: see text] metric potential. All the physical parameters like the matter density, radial and transverse pressure are regular inside the anisotropic star, with the speed of sound less than the speed of light. So the new solution obtained by us gives satisfactory description of realistic astrophysical compact stars. The model of this paper is compatible with observational data of compact objects like RX J1856-37, Her X-1, Vela X-12 and Cen X-3. A particular model of Her X-1 (Mass 0.98 [Formula: see text] and radius[Formula: see text]=[Formula: see text]6.7 km.) is studied in detail and found that it satisfies all the condition needed for physically acceptable model. Our model is described analytically as well as with the help of graphical representation.
THE BUSINESS MODEL PATTERN DATABASE — A TOOL FOR SYSTEMATIC BUSINESS MODEL INNOVATION
Authors: REMANE GERRIT , HANELT ANDRE , TESCH JAN F. , KOLBE LUTZ M.
Published: June 2016

Companies are more frequently seen shifting their focus from technological innovation towards business model innovation. One efficient option for business model innovation is to learn from existing solutions, i.e., business model patterns. However, the various understandings of the business model pattern concept are often confusing and contradictory, with the available collections incomplete, overlapping, and inconsistently structured. Therefore, the rich body of literature on business model patterns has not yet reached its full potential for both practical application as well as theoretic advancement. To help remedy this, we conduct an exhaustive review, filter for duplicates, and structure the patterns along several dimensions by applying a rigorous taxonomy-building approach. The resulting business model pattern database allows for navigation to the relevant set of patterns for a specific impact on a company’s business model. It can be used for systematic business model innovation, which we illustrate via a simplified case study.
Metastability effects in strained and stressed SrTiO3 films
Authors: Lebedev Alexander I.
Published: June 2016

The sequence of ground states for SrTiO3 film subjected to epitaxial strain as well as to mechanical stress along the [001] and [110] axes is calculated from first principles within the density functional theory. Under the fixed-strain boundary conditions, an increase in the lattice parameter of a substrate results in the [Formula: see text](II) sequence of ground states. Under the fixed-stress boundary conditions, the phase sequence is different and depends on how the stress is applied. It is revealed that the simultaneous presence of competing ferroelectric and antiferrodistortive instabilities in SrTiO3 gives rise to the appearance of metastable phases, whose number increases dramatically under the fixed-stress conditions. In the metastable phases, the octahedral rotation patterns are shown to differ substantially from those in the ground state. It is suggested that in systems with competing instabilities, each polar phase has its optimal octahedral rotation pattern which stabilizes this phase and creates a potential barrier preventing this phase to be transformed into other structures.
Progress in Top-Down Proteomics and the Analysis of Proteoforms
Authors: Toby Timothy K. , Fornelli Luca , Kelleher Neil L.
Published: June 2016

From a molecular perspective, enactors of function in biology are intact proteins that can be variably modified at the genetic, transcriptional, or post-translational level. Over the past 30 years, mass spectrometry (MS) has become a powerful method for the analysis of proteomes. Prevailing bottom-up proteomics operates at the level of the peptide, leading to issues with protein inference, connectivity, and incomplete sequence/modification information. Top-down proteomics (TDP), alternatively, applies MS at the proteoform level to analyze intact proteins with diverse sources of intramolecular complexity preserved during analysis. Fortunately, advances in prefractionation workflows, MS instrumentation, and dissociation methods for whole-protein ions have helped TDP emerge as an accessible and potentially disruptive modality with increasingly translational value. In this review, we discuss technical and conceptual advances in TDP, along with the growing power of proteoform-resolved measurements in clinical and translational research.
Nutrient-sensing mechanisms in hypothalamic cell models: neuropeptide regulation and neuroinflammation in male- and female-derived cell lines
Authors: Loganathan Neruja , Belsham Denise D.
Published: June 2016

The hypothalamus is responsible for the control of many of our physiological responses, including energy homeostasis. Of interest, there are a number of instances of sexual dimorphism documented with regard to metabolic processes. This review will discuss the necessity of utilizing both male and female models when studying the mechanisms underlying energy homeostasis, particularly those originating at the level of the hypothalamus. Because obesity often results in central neuroinflammation, we describe markers that could be used to study differences between male and female models, both the whole organism and also at the cellular level. Our laboratory has generated a wide array of immortalized hypothalamic cell models, originating from male and female rodents that we suggest could be beneficial for these types of studies. It is imperative that both sexes are considered before any recommendations for therapeutic interventions are considered.
Senescence in chronic allograft nephropathy
Authors: Sosa Peña María del Pilar , Lopez-Soler Reynold , Melendez J. Andrés
Published: June 2016

Despite increasing numbers of patients on dialysis, the numbers of renal transplants performed yearly have remained relatively static. During the last 50 years, there have been many advances in the pharmacology of prevention of organ rejection. However, most patients will suffer from a slow but steady decline in renal function leading to graft loss. The most common cause of long-term graft loss is chronic allograft nephropathy (CAN). Therefore, elucidating and understanding the mechanisms involved in CAN is crucial for achieving better posttransplant outcomes. It is thought that the development of epithelial to mesenchymal transition (EMT) in proximal tubules is one of the first steps towards CAN, and has been shown to be a result of cellular senescence. Cells undergoing senescence acquire a senescence associated secretory phenotype (SASP) leading to the production of interleukin-1 alpha (IL-1α), which has been implicated in several degenerative and inflammatory processes including renal disease. A central mediator in SASP activation is the production of reactive oxygen species (ROS), which are produced in response to numerous physiological and pathological stimuli. This review explores the connection between SASP and the development of EMT/CAN in an effort to suggest future directions for research leading to improved long-term graft outcomes.
Cln 3-requiring 9 is a negative regulator of Th17 pathway-driven inflammation in anti-glomerular basement membrane glomerulonephritis
Authors: Lee Hajeong , Lee Jae Wook , Yoo Kyung Don , Yoo Joo-Yeon , Lee Jung Pyo , Kim Dong Ki , Chin Ho Jun , Kim Yon Su , Yang Seung Hee
Published: June 2016

T helper 17 (Th17) lymphocytes promote renal inflammation in anti-glomerular basement membrane glomerulonephritis (anti-GBM GN), and signal transducer and activator of transcription 3 (STAT3) mediates activation of Th17 lymphocytes by IL-6 and transforming growth factor-β (TGF-β). Cln 3-requiring 9 (Ctr9), a subunit of RNA polymerase-associated factor complex (PAFc), regulates the transcription of IL-6/STAT3-dependent genes. Here, we investigated the role of Ctr9 in regulating Th17-driven inflammation in anti-GBM GN. In mice, STAT3β or IL-17 knockout ameliorated anti-GBM autoantibody-induced renal injury. This phenomenon was associated with decreases in retinoic acid receptor-related orphan receptor γt (RORγt), IL-17, phosphorylated STAT3, and proinflammatory cytokines. Compared with wild-type mice, Ctr9 increased in both STAT3β−/−and IL-17−/−mice injected with anti-GBM IgG, showing a negative correlation with Th17-related transcripts. Small interfering RNA (siRNA)-mediated knockdown of Ctr9 in intrarenal lymphocytes further upregulated Th17-related transcripts, consistent with repression of Th17 differentiation by Ctr9. Interestingly, Ctr9 was also expressed in human and mouse mesangial cells and downregulated in response to anti-GBM IgG or to TGF-β plus IL-17. Ctr9 in mesangial cells was even more repressed in the presence of both anti-GBM IgG and Th17-activating cytokines. Consistent with these findings, renal biopsies obtained from patients with anti-GBM GN showed consistent downregulation of Ctr9 and upregulation of phosphorylated STAT3 and IL-17 in the glomerulus. We conclude that Ctr9 is a negative regulator of Th17 differentiation in anti-GBM GN and repressed by anti-GBM IgG and IL-17 in mesangial cells.
Effect of current focusing on the sensitivity of inferior colliculus neurons to amplitude-modulated stimulation
Authors: George Shefin S. , Shivdasani Mohit N. , Fallon James B.
Published: June 2016

In multichannel cochlear implants (CIs), current is delivered to specific electrodes along the cochlea in the form of amplitude-modulated pulse trains, to convey temporal and spectral cues. Our previous studies have shown that focused multipolar (FMP) and tripolar (TP) stimulation produce more restricted neural activation and reduced channel interactions in the inferior colliculus (IC) compared with traditional monopolar (MP) stimulation, suggesting that focusing of stimulation could produce better transmission of spectral information. The present study explored the capability of IC neurons to detect modulated CI stimulation with FMP and TP stimulation compared with MP stimulation. The study examined multiunit responses of IC neurons in acutely deafened guinea pigs by systematically varying the stimulation configuration, modulation depth, and stimulation level. Stimuli were sinusoidal amplitude-modulated pulse trains (carrier rate of 120 pulses/s). Modulation sensitivity was quantified by measuring modulation detection thresholds (MDTs), defined as the lowest modulation depth required to differentiate the response of a modulated stimulus from an unmodulated one. Whereas MP stimulation showed significantly lower MDTs than FMP and TP stimulation ( P values <0.05) at stimulation ≤2 dB above threshold, all stimulation configurations were found to have similar modulation sensitivities at 4 dB above threshold. There was no difference found in modulation sensitivity between FMP and TP stimulation. The present study demonstrates that current focusing techniques such as FMP and TP can adequately convey amplitude modulation and are comparable to MP stimulation, especially at higher stimulation levels, although there may be some trade-off between spectral and temporal fidelity with current focusing stimulation.
Ampakine CX717 potentiates intermittent hypoxia-induced hypoglossal long-term facilitation
Authors: Turner S. M. , ElMallah M. K. , Hoyt A. K. , Greer J. J. , Fuller D. D.
Published: June 2016

Glutamatergic currents play a fundamental role in regulating respiratory motor output and are partially mediated by α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors throughout the premotor and motor respiratory circuitry. Ampakines are pharmacological compounds that enhance glutamatergic transmission by altering AMPA receptor channel kinetics. Here, we examined if ampakines alter the expression of respiratory long-term facilitation (LTF), a form of neuroplasticity manifested as a persistent increase in inspiratory activity following brief periods of reduced O2 [intermittent hypoxia (IH)]. Current synaptic models indicate enhanced effectiveness of glutamatergic synapses after IH, and we hypothesized that ampakine pretreatment would potentiate IH-induced LTF of respiratory activity. Inspiratory bursting was recorded from the hypoglossal nerve of anesthetized and mechanically ventilated mice. During baseline (BL) recording conditions, burst amplitude was stable for at least 90 min (98 ± 5% BL). Exposure to IH (3 × 1 min, 15% O2) resulted in a sustained increase in burst amplitude (218 ± 44% BL at 90 min following final bout of hypoxia). Mice given an intraperitoneal injection of ampakine CX717 (15 mg/kg) 10 min before IH showed enhanced LTF (500 ± 110% BL at 90 min). Post hoc analyses indicated that CX717 potentiated LTF only when initial baseline burst amplitude was low. We conclude that under appropriate conditions ampakine pretreatment can potentiate IH-induced respiratory LTF. These data suggest that ampakines may have therapeutic value in the context of hypoxia-based neurorehabilitation strategies, particularly in disorders with blunted respiratory motor output such as spinal cord injury.
Identification of the FirstDe Novo UBIAD1Gene Mutation Associated with Schnyder Corneal Dystrophy
Authors: Lin Benjamin R. , Frausto Ricardo F. , Vo Rosalind C. , Chiu Stephan Y. , Chen Judy L. , Aldave Anthony J.
Published: June 2016

Purpose.To report the identification of the firstde novo UBIAD1missense mutation in an individual with Schnyder corneal dystrophy (SCD).Methods.A slit lamp examination was performed on a 47-year-old woman without a family history of corneal disorders. The proband’s parents, two sisters, and son were also examined and genomic DNA from all six individuals was collected. The exons and exon-intron boundaries ofUBIAD1were screened using Sanger sequencing. Identified mutations were screened for in 200 control chromosomes.In silicoanalysis predicted the impact of identified mutations on protein function and structure.Results.Slit lamp examination of the proband revealed findings consistent with SCD. Corneas of the family members appeared unaffected. Screening ofUBIAD1in the proband identified a novel heterozygous c.308C>T mutation, predicted to encode the missense amino acid substitution p.(Thr103Ile). This mutation was not identified in any of the family members or in 200 control chromosomes and was predicted to be damaging to normal protein function and structure.Conclusions.We present a novel heterozygousde novomissense mutation inUBIAD1, p.(Thr103Ile), identified in a patient with classic clinical features of SCD. This highlights the value of genetic testing in clinical diagnostic settings, even in the absence of a positive family history.
Perceptions of the Role of Short-Term Volunteerism in International Development: Views from Volunteers, Local Hosts, and Community Members
Authors: Loiseau Bethina , Sibbald Rebekah , Raman Salem A. , Darren Benedict , Loh Lawrence C. , Dimaras Helen
Published: June 2016

Background.Short-term international volunteer trips traditionally involve volunteers from high-income countries travelling to low- and middle-income countries to assist in service-related development activities. Their duration typically ranges from 7 to 90 days. The city of La Romana, Dominican Republic, receives hundreds of short-term international volunteers annually. They participate in activities aimed at improving conditions faced by a marginalized ethnic-Haitian community living inbateyes. Methods.This qualitative analysis examined perceptions of short-term international volunteerism, held by three key stakeholder groups in La Romana: local hosts, international volunteers, and community members. Responses from semistructured interviews were recorded and analysed by thematic analysis.Results.Themes from the 3 groups were broadly categorized into general perceptions of short-term volunteerism and proposed best practices. These were further subdivided into perceptions of value, harms, and motivations associated with volunteer teams for the former and best practices around volunteer composition and selection, partnership, and skill sets and predeparture training for the latter.Conclusion.Notable challenges were associated with short-term volunteering, including an overemphasis on the material benefits from volunteer groups expressed by community member respondents; misalignment of the desired and actual skill sets of volunteers; duplicate and uncoordinated volunteer efforts; and the perpetuation of stereotypes suggesting that international volunteers possess superior knowledge or skills. Addressing these challenges is critical to optimizing the conduct of short-term volunteerism.
A Rising E-Channel Tide Lifts All Boats? The Impact of Manufacturer Multichannel Encroachment on Traditional Selling and Leasing
Authors: Yan Wei , Li Youwei , Wu Ying , Palmer Mark
Published: June 2016

Organizing and managing channels of distribution is an important marketing task. Due to the emergence of electronic commerce on the Internet, e-channel distribution systems have been adopted by many manufacturers. However, academic and anecdotal evidence both point to the pressures arising from this new e-channel manufacturing environment. Question marks therefore remain on how the addition of this e-channel affects the traditional marketing strategies of leasing and selling. We set up several two-period dual-channel models in which a manufacturer sells a durable product through both a manufacturer-owned e-channel and an independent reseller (leaser) who adopts selling (leasing) to consumers. Our main results indicate that, direct selling cost aside, product durability plays an important role in shaping the strategies of all members. With either marketing strategy, the additional expansion of an e-channel territory may secure Pareto gains, in which all members benefit.
Inflammatory Cardiomyopathy: A Current View on the Pathophysiology, Diagnosis, and Treatment
Authors: Krejci Jan , Mlejnek Dalibor , Sochorova Dana , Nemec Petr
Published: June 2016

Inflammatory cardiomyopathy is defined as inflammation of the heart muscle associated with impaired function of the myocardium. In our region, its etiology is most often viral. Viral infection is a possible trigger of immune and autoimmune mechanisms which contributed to the damage of myocardial function. Myocarditis is considered the most common cause of dilated cardiomyopathy. Typical manifestation of this disease is heart failure, chest pain, or arrhythmias. The most important noninvasive diagnostic method is magnetic resonance imaging, but the gold standard of diagnostics is invasive examination, endomyocardial biopsy. In a significant proportion of cases with impaired left ventricular systolic function, recovery occurs spontaneously in several weeks and therefore it is appropriate to postpone critical therapeutic decisions about 3–6 months after start of the treatment. Therapy is based on standard heart failure treatment; immunosuppressive or antimicrobial treatment may be considered in some cases depending on the results of endomyocardial biopsy. If severe dysfunction of the left ventricle persists, device therapy may be needed.
Characterization of a Twin-Entry Radial Turbine under Pulsatile Flow Condition
Authors: Cerdoun Mahfoudh , Ghenaiet Adel
Published: June 2016

In automotive applications radial gas turbines are commonly fitted with a twin-entry volute connected to a divided exhaust manifold, ensuring a better scavenge process owing to less interference between engines’ cylinders. This paper is concerned with the study of the unsteady performances related to the pulsating flows of a twin-entry radial turbine in engine-like conditions and the hysteresis-like behaviour during the pulses period. The results show that the aerodynamic performances deviate noticeably from the steady state and depend mainly on the time shifting between the actual output power and the isentropic power, which is distantly related to the apparent length. The maximum of efficiency and output shaft power are accompanied by low entropy generation through the shroud entry side, and their instantaneous behaviours tend to follow mainly the inlet total pressure curve. As revealed a billow is created by the interaction between the main flow and the infiltrated flow, affecting the flow incidence at rotor entry and producing high losses.
Solitary Spinal Epidural Metastasis from Prostatic Small Cell Carcinoma
Authors: Lee Kyung Ryeol , Maeng Young Hee
Published: June 2016

Solitary, spinal epidural metastasis (SEM) that is not related to vertebral metastasis is very rare. And solitary SEM from prostatic cancer is rarely found in previously published reports. However, it is clinically significant due to the possibility of neurologic dysfunction, and it can be assessed by MRI. In this report, we show a case of solitary SEM arising from prostatic small cell carcinoma detected by MRI.
Breast Cancer in Africa: Limitations and Opportunities for Application of Genomic Medicine
Authors: Silverstein Allison , Sood Rachita , Costas-Chavarri Ainhoa
Published: June 2016

As genomic medicine gains clinical applicability across a spectrum of diseases, insufficient application in low-income settings stands to increase health disparity. Breast cancer screening, diagnosis, and treatment have benefited greatly from genomic medicine in high-income settings. As breast cancer is a leading cause of both cancer incidence and mortality in Africa, attention and resources must be applied to research and clinical initiatives to integrate genomic medicine into breast cancer care. In terms of research, there is a paucity of investigations into genetic determinants of breast cancer specific to African populations, despite consensus in the literature that predisposition and susceptibility genes vary between populations. Therefore, we need targeted strengthening of existing research efforts and support of new initiatives. Results will improve clinical care through screening and diagnosis with genetic testing specific to breast cancer in African populations. Clinically, genomic medicine can provide information capable of improving resource allocation to the population which most stands to benefit from increased screening or tailored treatment modalities. In situations where mammography or chemotherapy options are limited, this information will allow for the greatest impact. Implementation of genomic medicine will face numerous systemic barriers but is essential to improve breast cancer outcomes and survival.
Estimation of Concrete Carbonation Depth Considering Multiple Influencing Factors on the Deterioration of Durability for Reinforced Concrete Structures
Authors: Cho Hae-Chang , Ju Hyunjin , Oh Jae-Yuel , Lee Kyung Jin , Hahm Kyung Won , Kim Kang Su
Published: June 2016

While the durability of concrete structures is greatly influenced by many factors, previous studies typically considered only a single durability deterioration factor. In addition, these studies mostly conducted their experiments inside the laboratory, and it is extremely hard to find any case in which data were obtained from field inspection. Accordingly, this study proposed an Adaptive Neurofuzzy Inference System (ANFIS) algorithm that can estimate the carbonation depth of a reinforced concrete member, in which combined deterioration has been reflected based on the data obtained from field inspections of 9 buildings. The proposed ANFIS algorithm closely estimated the carbonation depths, and it is considered that, with further inspection data, a higher accuracy would be achieved. Thus, it is expected to be used very effectively for durability estimation of a building of which the inspection is performed periodically.
Comparison of Medical Adhesive Tapes in Patients at Risk of Facial Skin Trauma under Anesthesia
Authors: Zeng Ling Antonia , Lie Sui An , Chong Shin Yuet
Published: June 2016

Introduction. Adhesive tapes are used for taping eyelids closed and securing endotracheal tubes during general anesthesia. These tapes can cause facial skin injury. We compared the incidence of facial skin injury and patient satisfaction with different tapes used.Methods. A total of 60 adult patients at risk of skin trauma were randomized to use 3M™Kind Removal Silicone Tape or standard acrylate tapes: 3M Durapore (endotracheal tube) and Medipore (eyelids). Patients were blinded to tape used. Postoperatively, a blinded recovery nurse assessed erythema, edema, and denudation of skin. Anesthesiologist in charge also assessed skin injury. On postoperative day 1, patients rated satisfaction with the condition of their skin over the eyelids and face on a 5-point Likert scale.Results. More patients had denudation of skin with standard tapes, 4 (13.3%) versus 0 with silicone tape (p=0.026) and in anesthesiologist-evaluated skin injury 11 (37%) with standard versus 1 (3%) with silicone (p=0.002). No significant differences were found in erythema and edema. Patient satisfaction score was higher with silicone tape: over eyelids: mean 3.83 (standard) versus 4.53 (silicone), Mann-WhitneyUtest,p<0.001; over face: mean 3.87 (standard) versus 4.57 (silicone) (p<0.001).Conclusion. Silicone tape use had less skin injury and greater patient satisfaction than standard acrylate tapes.
Tacrolimus for Remission Induction and Maintenance Therapy in Patients with Ulcerative Colitis: A Retrospective Evaluation Study
Authors: Ito Ayumi , Iizuka Bunei , Omori Teppei , Nakamura Shinichi , Tokushige Katsutoshi
Published: June 2016

Background. In this retrospective study, we compared the efficacy of tacrolimus (TAC) or prednisolone (PSL) for maintenance therapy in patients with ulcerative colitis (UC) at remission.Methods. The study patients were followed up for at least one year after induction of remission with either PSL (n=55, between April 2004 and March 2014) or TAC (n=40, between April 2009 and March 2014). The clinical features and relapse rates were compared in the two groups. Maintenance therapy in the TAC group included TAC alone, AZA alone, and TAC plus AZA.Results. The recurrence rates at 1500 days after remission were 61% and 46% for the PSL and TAC groups, respectively (P<0.05). The recurrence rates at 600 days for TAC, AZA, and TAC + AZA maintenance groups were 24%, 49%, and 55%, respectively. Nephrotoxicity developed in 16 patients on TAC maintenance therapy.Conclusions. TAC monotherapy is a potential alternative especially for PSL nonresponders or those intolerant to AZA. However, patients on TAC therapy should be regularly monitored for adverse effects including nephrotoxicity.
Poly-γ-Glutamic Acid Nanoparticles Based Visible Light-Curable Hydrogel for Biomedical Application
Authors: Bakó József , Kerényi Farkas , Hrubi Edit , Varga István , Daróczi Lajos , Dienes Beatrix , Csernoch László , Gáll József , Hegedűs Csaba
Published: June 2016

Nanoparticles and hydrogels have gained notable attention as promising potential for fabrication of scaffolds and delivering materials. Visible light-curable systems can allow for the possibility ofin situfabrication and have the advantage of optimal applicability. In this study nanogel was created from methacrylated poly-gamma-glutamic acid nanoparticles by visible (dental blue) light photopolymerization. The average size of the particles was 80 nm by DLS, and the NMR spectra showed that the methacrylation rate was 10%. Polymerization time was 3 minutes, and a stable nanogel with a swelling rate of 110% was formed. The mechanical parameters of the prepared structure (compression stress 0.73 MPa, and Young’s modulus 0.93 MPa) can be as strong as necessary in a real situation, for example, in the mouth. A retaining effect of the nanogel was found for ampicillin, and the biocompatibility of this system was tested by Alamar Blue proliferation assay, while the cell morphology was examined by fluorescence and laser scanning confocal microscopy. In conclusion, the nanogel can be used for drug delivery, or it can be suitable for a control factor in different systems.
Epithelial Anion Transport as Modulator of Chemokine Signaling
Authors: Schnúr Andrea , Hegyi Péter , Rousseau Simon , Lukacs Gergely L. , Veit Guido
Published: June 2016

The pivotal role of epithelial cells is to secrete and absorb ions and water in order to allow the formation of a luminal fluid compartment that is fundamental for the epithelial function as a barrier against environmental factors. Importantly, epithelial cells also take part in the innate immune system. As a first line of defense they detect pathogens and react by secreting and responding to chemokines and cytokines, thus aggravating immune responses or resolving inflammatory states. Loss of epithelial anion transport is well documented in a variety of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, pancreatitis, and cholestatic liver disease. Here we review the effect of aberrant anion secretion with focus on the release of inflammatory mediators by epithelial cells and discuss putative mechanisms linking these transport defects to the augmented epithelial release of chemokines and cytokines. These mechanisms may contribute to the excessive and persistent inflammation in many respiratory and gastrointestinal diseases.
Functionalized Solid-Sphere PEG-b-PCL Nanoparticles to Target Brain Capillary Endothelial CellsIn Vitro
Authors: Grossen Philip , Québatte Gabriela , Witzigmann Dominik , Prescianotto-Baschong Cristina , Dieu Le-Ha , Huwyler Jörg
Published: June 2016

Nanoparticles are increasingly used to implement drug targeting strategies. In the present study, solid-sphere nanoparticles (SNPs) made of poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) were covalently linked to a monoclonal antibody (83-14 mAb) targeted against the human insulin receptor that is highly expressed on human brain microvascular endothelial cells. Resulting targeted SNPs were characterized using transmission electron microscopy (TEM), cryo-TEM, dynamic light scattering, and fluorescence correlation spectroscopy. The critical aggregation concentration was determined using a fluorescence approach. Interaction with a well-characterized humanin vitromodel of the blood-brain barrier (hCMEC/D3) was analysed using an array of methods (flow cytometry, confocal laser scanning microscopy, and TEM). The toxicity on hCMEC/D3 cells and in addition on the human liver cell line HepG2 was assessed using the MTT assay. SNPs with a diameter of 80 nm and a homogeneous size distribution were obtained. Successful conjugation of 83-14 mAb using a heterobifunctional linker resulted in 5-6 molecules of fluorescently labeled 83-14 mAb per SNP. Functionalized SNPs were taken up by hCMEC/D3 cells efficiently without showing a significant toxic effect on cells of the blood-brain barrier and HepG2 cells. These results indicate that functionalized PEG-b-PCL SNPs are a promising candidate to deliver drugs to the CNS.