bluuebunny/crossref_metadata_2025 huggingface dataset:
Plaque formation and the intraneuronal accumulation of β‐amyloid in Alzheimer's disease
Authors: Takahashi Reisuke H. , Nagao Toshitaka , Gouras Gunnar K.
Published: March 2017

Amyloid plaques and neurofibrillary tangles (NFTs) in the brain are the neuropathological hallmarks of Alzheimer's disease (AD). Amyloid plaques are composed of β‐amyloid peptides (Aβ), while NFTs contain hyperphosphorylated tau proteins. Patients with familial AD who have mutations in the amyloid precursor protein (APP) gene have either increased production of Aβ or generate more aggregation‐prone forms of Aβ. The findings of familial AD mutations in the APP gene suggest that Aβ plays a central role in the pathophysiology of AD. Aβ42, composed of 42 amino acid residues, aggregates readily and is considered to form amyloid plaque. However, the processes of plaque formation are still not well known. It is generally thought that Aβ is secreted into the extracellular space and aggregates to form amyloid plaques. Aβ as extracellular aggregates and amyloid plaques are thought to be toxic to the surrounding neurons. The intraneuronal accumulation of Aβ has more recently been demonstrated and is reported to be involved in synaptic dysfunction, cognitive impairment, and the formation of amyloid plaques in AD. We herein provide an overview of the process of the intraneuronal accumulation of Aβ and plaque formation, and discuss its implications for the pathology, early diagnosis, and therapy of AD.
A multistudy examination of organizational stressors, emotional labor, burnout, and turnover in sport organizations
Authors: Larner R. J. , Wagstaff C. R. D. , Thelwell R. C. , Corbett J.
Published: March 2017

While a growing body of research has examined the types of organizational stressors encountered by individuals and their allied responses, little is known about how such individuals manage their emotional responses to these stressors or the consequences of such behaviors. This article presents novel findings from two studies examining the moderating role that emotional labor plays in the relationship between the frequency of organizational stressor experience, burnout, turnover intentions, and actual turnover in sport. In study 1, participants (n=487) completed measures of organizational stressors (OSI‐SP), emotional labor (ELS), burnout (ABQ), and turnover intentions. In study 2, a 6‐month longitudinal design was used to examine measures of organizational stressors (OSI‐SP), emotional labor (ELS), turnover intentions, and actual turnover. Study 1 showed that surface acting moderated the relationship between the frequency of organizational stressors and burnout in sport. Further, surface acting acted as an important mechanism through which burnout mediated the relationship between the frequency of organizational stressors and turnover intentions. Study 2 showed that surface acting moderated the relationship between the organizational stressor frequency and turnover intentions—but not actual turnover—over time. These results highlight the importance of surface acting in understanding how individuals respond to organizational stressors encountered in sport, expanding our understanding of the positive and negative responses component of the meta‐model of stress, emotions, and performance. These findings also highlight potentially deleterious emotion‐management behaviors that practitioners might consider when aiming to support individuals encountering organizational stressors in sport.
Disasters and Social Capital: Exploring the Impact of Hurricane Katrina on Gulf Coast Counties
Authors: Wang Lili , Ganapati Nazife Emel
Published: March 2017

Objective

This article examines the impact of disasters on social capital in the context of Hurricane Katrina.

Method

One hundred eighty‐two counties affected by Hurricane Katrina are included in the study. Disaster‐related data, social capital, and community characteristics of these counties three years before and three years after the disaster are analyzed using a longitudinal fixed‐effect model.

Results

Hurricane Katrina slowed down the growth of social capital, but growth gradually recovered following the disaster. After controlling for community characteristics, areas that received more federal government assistance experienced stronger growth in social capital post‐Katrina. Additionally, metropolitan areas with a higher percentage of senior population, higher ethnic diversity, more per capita housing units, and lower population density appear to have had higher levels of social capital.

Conclusion

Disasters could hinder the growth of social capital and federal disaster assistance could potentially alleviate the negative impact.
Do Airports Boost Economic Development by Attracting Talent? An Empirical Investigation at the Subcounty Level
Authors: Chen Xinxiang , Chi Guanghua , Chi Guangqing
Published: March 2017

Objective

The objectives of this study were to examine (1) the linkage from airports to regional talent distribution and (2) the effect of talent on regional economic development.

Methods

Using the data collected in Wisconsin at the municipal level, a subcounty level, in a region of the North Central United States from 1970 to 2010 and the American Community Survey 2006–2010 five‐year estimates, and random effects models and structural equation models, we employ descriptive and inferential statistics to examine the linkage from airports to talent to regional economic development.

Results

We find that the farther a location is away from the airport, the lower its talent share tends to be, while greater passenger flow at the nearest airport increases a location's talent share. Given the quantity of passenger flow, a longer distance from the airport also reduces a location's talent share. The results furthermore suggest that economic development is impacted positively by passenger flow and talent share and negatively by distance to an airport.

Conclusion

Our results underscore the intermediate role of talent between airports and regional economic development; building the linkage from airports to talent within the context of regional economic development provides important insights for local policy making aimed at attracting talented migrants.
Hispanics’ Behavioral Intentions Toward Energy Conservation: The Role of Sociodemographic, Informational, and Attitudinal Variables
Authors: Takahashi Bruno , Duan Ran , Van Witsen Anthony
Published: March 2017

Objectives

This study is aimed at examining energy‐related behavioral intention among Hispanics in the United States. It examines the role of nationality and geographic location, as well as informational and attitudinal factors.

Method

The study used survey data from the University of Texas at Austin Energy Poll. Data were analyzed using ANOVA and regressions analysis.

Results

Results show that Hispanics overall in the West had higher levels of intention to save energy than those in any other region, while there is no clear pattern indicating that intentions to save energy were linked to Hispanics' ethnic groups. Besides information dissemination and various measures of environmental concern, belief and interest were strongly related to energy‐related behavioral intentions.

Conclusions

Findings contribute to the understanding of Hispanics’ energy behaviors, concluding that environmentalism and information dissemination are important predictors of behavioral intention within the Hispanic population.
Reviewer Acknowledgements
Authors: Willianms Ellery
Published: March 2017

Business and Management Studies (BMS) would like to acknowledge the following reviewers for their assistance with peer review of manuscripts for this issue. Many authors, regardless of whether BMS publishes their work, appreciate the helpful feedback provided by the reviewers. Their comments and suggestions were of great help to the authors in improving the quality of their papers. Each of the reviewers listed below returned at least one review for this issue.Reviewers for Volume 3, Number 1 Andrzej Niemiec, Poznań University of Economics and Business, PolandChrister Thörnqvist, University of Skövde, SwedenGongyan Yang, Liaoning University, ChinaJulia Stefanova, Nagoya Gakuin University, BulgariaMike Rayner, University of Portsmouth, UKMohammad Soliman, Fayoum University, EgyptMythili Kolluru, Ibra College of Technology, OmanOlha Komelina, Yuri Kondratyuk University, UkraineOnur Dogan, Dokuz Eylül University, TurkeyRashedul Hasan, International Islamic University Malaysia, MalaysiaRegina Lenart-Gansiniec, Jagiellonian University, PolandRocsana Tonis, Spiru Haret University, RomaniaRuoniu Wang, University of Florida, USAXhavit Islami, University of Prishtina, KosovoZeki Atıl Bulut, Dokuz Eylul University, Turkey          Ellery WillianmsEditorial AssistantOn behalf of,The Editorial Board of Business and Management StudiesRedfame Publishing9450 SW Gemini Dr. #99416Beaverton, OR 97008, USAURL: http://bms.redfame.com
Higher symmetries of powers of the Laplacian and rings of differential operators
Authors: Levasseur T. , Stafford J. T.
Published: March 2017

We study the interplay between the minimal representations of the orthogonal Lie algebra $\mathfrak{g}=\mathfrak{so}(n+2,\mathbb{C})$ and the algebra of symmetries$\mathscr{S}(\Box ^{r})$ of powers of the Laplacian $\Box$ on $\mathbb{C}^{n}$. The connection is made through the construction of a highest-weight representation of $\mathfrak{g}$ via the ring of differential operators ${\mathcal{D}}(X)$ on the singular scheme $X=(\mathtt{F}^{r}=0)\subset \mathbb{C}^{n}$, for $\mathtt{F}=\sum _{j=1}^{n}X_{i}^{2}\in \mathbb{C}[X_{1},\ldots ,X_{n}]$. In particular, we prove that $U(\mathfrak{g})/K_{r}\cong \mathscr{S}(\Box ^{r})\cong {\mathcal{D}}(X)$ for a certain primitive ideal $K_{r}$. Interestingly, if (and only if) $n$ is even with $r\geqslant n/2$, then both $\mathscr{S}(\Box ^{r})$ and its natural module ${\mathcal{A}}=\mathbb{C}[\unicode[STIX]{x2202}/\unicode[STIX]{x2202}X_{n},\ldots ,\unicode[STIX]{x2202}/\unicode[STIX]{x2202}X_{n}]/(\Box ^{r})$ have a finite-dimensional factor. The same holds for the ${\mathcal{D}}(X)$-module ${\mathcal{O}}(X)$. We also study higher-dimensional analogues $M_{r}=\{x\in A:\Box ^{r}(x)=0\}$ of the module of harmonic elements in $A=\mathbb{C}[X_{1},\ldots ,X_{n}]$ and of the space of ‘harmonic densities’. In both cases we obtain a minimal $\mathfrak{g}$-representation that is closely related to the $\mathfrak{g}$-modules ${\mathcal{O}}(X)$ and ${\mathcal{A}}$. Essentially all these results have real analogues, with the Laplacian replaced by the d’Alembertian $\Box _{p}$ on the pseudo-Euclidean space $\mathbb{R}^{p,q}$ and with $\mathfrak{g}$ replaced by the real Lie algebra $\mathfrak{so}(p+1,q+1)$.
On log del Pezzo surfaces in large characteristic
Authors: Cascini Paolo , Tanaka Hiromu , Witaszek Jakub
Published: March 2017

We show that any Kawamata log terminal del Pezzo surface over an algebraically closed field of large characteristic is globally$F$-regular or it admits a log resolution which lifts to characteristic zero. As a consequence, we prove the Kawamata–Viehweg vanishing theorem for klt del Pezzo surfaces of large characteristic.
Gene editing for skin diseases: designer nucleases as tools for gene therapy of skin fragility disorders
Authors: March Oliver P. , Reichelt Julia , Koller Ulrich
Published: March 2017

New Findings

What is the topic of this review?

This review concerns current gene editing strategies for blistering skin diseases with respect to individual genetic constellations and distinct conditions.

What advances does it highlight?

Specificity and safety dominate the discussion of gene editing applications for gene therapy, where a number of tools are implemented. Recent developments in this rapidly progressing field pose further questions regarding which tool is best suited for each particular use.

The current treatment of inherited blistering skin diseases, such as epidermolysis bullosa (EB), is largely restricted to wound care and pain management. More effective therapeutic strategies are urgently required, and targeting the genetic basis of these severe diseases is now within reach. Here, we describe current gene editing tools and their potential to correct gene function in monogenetic blistering skin diseases. We present the features of the most frequently used gene editing techniques, transcription activator‐like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats/CRISPR‐associated protein 9 (CRISPR/Cas9), determining their preferential application for specific genetic conditions, including the type of mutational inheritance, the targeting site within the gene or the possibility to target the mutation specifically. Both tools have traits beneficial in specific situations. Promising developments in the field engender gene editing as a potentially powerful therapeutic option for future clinical applications.
Prostacyclin does not affect sweating but induces skin vasodilatation to a greater extent in older versus younger women: roles of NO and KCa channels
Authors: Fujii Naoto , McNeely Brendan D. , Nishiyasu Takeshi , Kenny Glen P.
Published: March 2017

New Findings

What is the central question of this study?

It remains unknown whether ageing modulates prostacyclin‐induced cutaneous vasodilatation in women.

What is the main finding and its importance?

Prostacyclin induced cutaneous vasodilatation, albeit the magnitude of increase at lower concentrations of prostacyclin was greater in older relative to young women. This response was associated with greater contributions of nitric oxide synthase and calcium‐activated potassium channels. Our results suggest that administration of prostacyclin might be an effective therapy to reverse microvascular hypoperfusion, especially in older women.

We previously reported that prostacyclin induces cutaneous vasodilatation but not sweating in younger and older men. Furthermore, we demonstrated that nitric oxide synthase and calcium‐activated potassium (KCa) channels contribute to the prostacyclin‐induced cutaneous vasodilatation in younger men, although these contributions are diminished in older men. Given that the effects of ageing might differ between men and women, the above results cannot simply be applied to women. In this study, cutaneous vascular conductance and sweat rate were evaluated in younger (mean ± SD, 22 ± 3 years old) and older (55 ± 7 years old) women (10 per group) at four intradermal forearm skin sites treated as follows: (i) lactated Ringer solution without any drug (control); (ii) 10 mm NG‐nitro‐l‐arginine (l‐NNA), a non‐specific nitric oxide synthase inhibitor; (iii) 50 mm tetraethylammonium (TEA), a non‐specific KCa channel blocker; or (iv) 10 mm l‐NNA plus 50 mm TEA. All four sites were co‐administered with prostacyclin in an incremental manner (0.04, 0.4, 4, 40 and 400 μm, each for 25 min). Surprisingly, increases in cutaneous vascular conductance in response to 0.04–4 μm prostacyclin were greater in older relative to younger women (all P ≤ 0.05), and these age‐related differences were diminished when both l‐NNA and TEA were administered simultaneously (all P > 0.05). No effect on sweat rate was observed in either group (all concentrations, P > 0.05). We show that although prostacyclin does not mediate sweating, it induces cutaneous vasodilatation, and this response elicited by lower concentrations of prostacyclin is greater in older relative to younger women. This greater cutaneous vasodilatation in older women is likely to be attributable to nitric oxide synthase‐ and KCa channel‐dependent mechanisms.
Influence of Morphology on Flow Law Characteristics in Open-Cell Foams: An Overview of Usual Approaches and Correlations
Authors: Kumar Prashant , Topin Frédéric
Published: March 2017

Foam structures have been a subject of intensive research since the last decade. The pore space in open-cell foam is interconnected, forming perforated channels of varying cross-sectional areas where fluid can flow. Knowledge of pressure drop induced by these foam matrices is essential for successful design and operation of high-performance industrial systems. In this context, analytical correlations were derived for the determination of Darcian permeability (KD) and Forchheimer inertia coefficient (CFor) in open-cell foams of different strut shapes. It has been shown that the flow law characteristics are strongly dependent on strut shape, strut characteristic dimension, and length. The applicability of new correlations was examined by comparing and validating the numerical and experimental flow law characteristics data against the predicted ones. An excellent agreement has been observed for the foam structures of different materials and variable texture in a wide range of porosity and Reynolds number.
Experimental Study of Load Variations on Pressure Fluctuations in a Prototype Reversible Pump Turbine in Generating Mode
Authors: Zhang Yuning , Chen Ting , Li Jinwei , Yu Jixing
Published: March 2017

The characteristics of pressure fluctuations in a prototype reversible pump turbine (RPT) is investigated within a wide range of load conditions with a focus on the low-load condition (e.g., 25% of rated power) with the aid of pressure signals obtained at several typical recording points (i.e., spiral casing, vaneless space, draft tube cone, and draft tube elbow). Our findings reveal that at the low-load condition, the pressure fluctuation is quite significant (e.g., above 12% in terms of nondimensional values), especially in the vaneless space and spiral casing with the dominant frequency being the blade passing frequency. Furthermore, based on the characteristics of pressure fluctuation, the investigated load range is divided into three zones. For zone I (with low load), the amplitude of pressure fluctuation is highest and the dominant mechanism is the rotor–stator interaction in the vaneless space with the blade passing frequency. For zone II (with medium load), the amplitude of pressure fluctuation is less prominent (below 5%) and the dominant mechanism is the low-frequency fluctuations induced by the swirling vortex rope. For zone III (with high load), the amplitude of pressure fluctuation is quite limited (less than 3%) and the dominant mechanism is still the rotor–stator interaction but with the dominant frequency being the harmonics of blade passing frequency. Detailed examples for all three zones are given and discussed with quantitative descriptions of propagation mechanism of fluctuation.
Water Droplet Adhesion on Hydrophobic Surfaces: Influence of Droplet Size and Inclination Angle of Surface on Adhesion Force
Authors: Al-Sharafi Abdullah , Yilbas Bekir S. , Ali Haider
Published: March 2017

Adhesion of various size sessile droplets on the hydrophobic surfaces is considered, and the moment generated about the locus of the droplet meniscus is determined for several inclination angles of hydrophobic surface. An experiment is designed to examine the influence of inclination of hydrophobic surface on the water droplet behavior. The flow field generated inside the droplet is simulated to predict the flow acceleration and its effects on adhesion force. Simulations are repeated for different inclination angles of hydrophobic surface. The flow predictions are validated through the experimental data. It is found that the moment about the locus of droplet meniscus increases with increasing inclination angle, which is more pronounced for the large volume water droplets, such as ∀ = 45 μL; however, further increase of inclination angle lowers the moment because of significant change of the location of the line of action of the total force during the excessive body deformation of the droplet. The flow field developed inside the droplet forms a circulation cell, and the orientation and size of the circulation cell change with droplet volume, which becomes significant at high inclination angles. The flow acceleration inside the droplet does not have significant contribution to the overall force generated on the droplet during the inclination of the hydrophobic surface. The shear force generated at the wetted surface of the droplet plays in significant role on the adhesion force.
A Robust Approach to Quantification of Margin and Uncertainty
Authors: Segalman Daniel J. , Paez Thomas L. , Bauman Lara E.
Published: March 2017

A systematic approach to defining margin in a manner that incorporates statistical information and accommodates data uncertainty but does not require assumptions about specific forms of the tails of distributions is developed. A margin that is insensitive to the character of the tails of the relevant distributions (tail insensitive margin, TIM) is defined. This is complemented by the calculation of probability of failure (PoF) where the load distribution is augmented by a quantity equal to the TIM. This approach avoids some of the perplexing results common to traditional reliability theory where, on the basis of very small amounts of data, one is led to extraordinary claims of infinitesimal probability of failure. Additionally, this approach permits a more meaningful separation of statistical and engineering issues.
Time domain reconstruction of sound speed and attenuation in ultrasound computed tomography using full wave inversion
Authors: Pérez-Liva M. , Herraiz J. L. , Udías J. M. , Miller E. , Cox B. T. , Treeby B. E.
Published: March 2017

Ultrasound computed tomography (USCT) is a non-invasive imaging technique that provides information about the acoustic properties of soft tissues in the body, such as the speed of sound (SS) and acoustic attenuation (AA). Knowledge of these properties can improve the discrimination between benign and malignant masses, especially in breast cancer studies. Full wave inversion (FWI) methods for image reconstruction in USCT provide the best image quality compared to more approximate methods. Using FWI, the SS is usually recovered in the time domain, and the AA is usually recovered in the frequency domain. Nevertheless, as both properties can be obtained from the same data, it is desirable to have a common framework to reconstruct both distributions. In this work, an algorithm is proposed to reconstruct both the SS and AA distributions using a time domain FWI methodology based on the fractional Laplacian wave equation, an adjoint field formulation, and a gradient-descent method. The optimization code employs a Compute Unified Device Architecture version of the software k-Wave, which provides high computational efficiency. The performance of the method was evaluated using simulated noisy data from numerical breast phantoms. Errors were less than 0.5% in the recovered SS and 10% in the AA.
Angular coherence in ultrasound imaging: Theory and applications
Authors: Li You Leo , Dahl Jeremy J.
Published: March 2017

The popularity of plane-wave transmits at multiple transmit angles for synthetic transmit aperture (or coherent compounding) has spawned a number of adaptations and new developments of ultrasonic imaging. However, the coherence properties of backscattered signals with plane-wave transmits at different angles are unknown and may impact a subset of these techniques. To provide a framework for the analysis of the coherence properties of such signals, this article introduces the angular coherence theory in medical ultrasound imaging. The theory indicates that the correlation function of such signals forms a Fourier transform pair with autocorrelation function of the receive aperture function. This conclusion can be considered as an extended form of the van Cittert Zernike theorem. The theory is validated with simulation and experimental results obtained on speckle targets. On the basis of the angular coherence of the backscattered wave, a new short-lag angular coherence beamformer is proposed and compared with an existing spatial-coherence-based beamformer. An application of the theory in phase shift estimation and speed of sound estimation is also presented.
Deactivating stimulation sites based on low-rate thresholds improves spectral ripple and speech reception thresholds in cochlear implant users
Authors: Zhou Ning
Published: March 2017

The study examined whether the benefit of deactivating stimulation sites estimated to have broad neural excitation was attributed to improved spectral resolution in cochlear implant users. The subjects' spatial neural excitation pattern was estimated by measuring low-rate detection thresholds across the array [see Zhou (2016). PLoS One 11, e0165476]. Spectral resolution, as assessed by spectral-ripple discrimination thresholds, significantly improved after deactivation of five high-threshold sites. The magnitude of improvement in spectral-ripple discrimination thresholds predicted the magnitude of improvement in speech reception thresholds after deactivation. Results suggested that a smaller number of relatively independent channels provide a better outcome than using all channels that might interact.
Unit of Analysis: Impact of Silverman and Solmon’s Article on Field-Based Intervention Research in Physical Education in the U.S.A.
Authors: Li Weidong , Xiang Ping , Chen Yung-Ju , Xie Xiuye , Li Yilin
Published: March 2017

Purpose:

The purposes of this study were to: (a) examine the impact of the Silverman and Solmon article (1998) on how researchers handle the unit of analysis issue in their field-based intervention research in physical education in the United States and summarize statistical approaches that have been used to analyze the data, and (b) provide recommendations for future field-based intervention research and related statistical analysis.

Methods:

We identified and coded 50 peer-reviewed, field-based intervention research articles with a coding template, published in Journal of Teaching in Physical Education and Research Quarterly for Exercise and Sport from 1998 to January 2016.

Results:

Our findings showed that 60% of the articles disregarded the unit of analysis and 80% of the articles applied the interventions to classes/groups, but used individual students as unit of analysis. Eight statistical modeling and analysis approaches were used to address the unit of analysis issue.

Discussion:

These findings provide first empirical evidence that the Silverman and Solmon 1998 article had limited impact on how researchers handle unit of analysis in their field-based intervention research in physical education. This suggests that the issue of unit of analysis remains largely unsolved. To address this problem, two experimental designs and corresponding statistical analysis methods were recommended.
2016 The Year That Was: Bone Strength
Authors: Janz Kathleen F.
Published: March 2017

Of all the lifestyle strategies for increasing bone strength during the growing years, physical activity is one of the most efficacious. This commentary highlights two exceptional 2016 publications addressing bone strength in children and adolescents with an eye toward reduced fracture risk later in life. The first by Weaver et al. was selected due to its comprehensive approach to understanding bone development. The second by Mitchell et al explores a new field of inquiry, that is, genetic-environment interaction as represented by bone mineral density-lowering alleles and high-impact physical activity. It is a first look at future precision medicine as it may pertain to pediatric bone strength.
Childhood Obesity, Physical Activity, and Exercise
Authors: Nemet Dan
Published: March 2017

As the incidence of childhood obesity increases, there is a need to promote leisure time physical activity. Traditional approaches to promote the population physical activity levels have shown at best moderate improvements. High percentage of children today carry a cell phone, thus the use of this portable device seems promising for enhancing physical activity.

Pokémon Go, is a smartphone game that uses augmented reality, where players are incentivized to get out and walk significant distances to catch the Pokémon. Initial reports suggested increases in the number of steps that players performed, yet this effect of the game was not sustained. Incorporating physical activity into modern technology seems promising, clearly there is need to explore creative ways to achieve a longer term effect.
Metabolism and Exercise During Youth
Authors: Tolfrey Keith , Zakrzewski-Fruer Julia K. , Smallcombe James
Published: March 2017

Three publications were selected based on the strength of the research questions, but also because they represent different research designs that are used with varying degrees of frequency in the pediatric literature. The first, a prospective, longitudinal cohort observation study from 7 to 16 years with girls and boys reports an intrinsic reduction in absolute resting energy expenditure after adjustment for lean mass, fat mass, and biological maturity. The authors suggest this could be related to evolutionary energy conservation, but may be problematic now that food energy availability is so abundant. The second focuses on the effect of acute exercise on neutrophil reactive oxygen species production and inflammatory markers in independent groups of healthy boys and men. The authors suggested the boys experienced a “sensitized” neutrophil response stimulated by the exercise bout compared with the men; moreover, the findings provided information necessary to design future trials in this important field. In the final study, a dose-response design was used to examine titrated doses of high intensity interval training on cardiometabolic outcomes in adolescent boys. While the authors were unable to identify a recognizable dose-response relationship, there are several design strengths in this study, which was probably underpowered.
The Cell Wall Lipid PDIM Contributes to Phagosomal Escape and Host Cell Exit ofMycobacterium tuberculosis
Authors: Quigley Jeff , Hughitt V. Keith , Velikovsky Carlos A. , Mariuzza Roy A. , El-Sayed Najib M. , Briken Volker
Published: March 2017

The cell wall ofMycobacterium tuberculosisis composed of unique lipids that are important for pathogenesis. Indeed, the first-ever genetic screen inM. tuberculosisidentified genes involved in the biosynthesis and transport of the cell wall lipid PDIM (phthioceroldimycocerosates) as crucial for the survival ofM. tuberculosisin mice. Here we show evidence for a novel molecular mechanism of the PDIM-mediated virulence inM. tuberculosis. We characterized the DNA interaction and the regulon of Rv3167c, a transcriptional repressor that is involved in virulence regulation ofM. tuberculosis, and discovered that it controls the PDIM operon. A loss-of-function genetic approach showed that PDIM levels directly correlate with the capacity ofM. tuberculosisto escape the phagosome and induce host cell necrosis and macroautophagy. In conclusion, our study attributes a novel role of the cell wall lipid PDIM in intracellular host cell modulation, which is important for host cell exit and dissemination ofM. tuberculosis.

IMPORTANCEMycobacterium tuberculosisis a major human pathogen that has coevolved with its host for thousands of years. The complex and unique cell wall ofM. tuberculosiscontains the lipid PDIM (phthioceroldimycocerosates), which is crucial for virulence of the bacterium, but its function is not well understood. Here we show that PDIM expression byM. tuberculosisis negatively regulated by a novel transcriptional repressor, Rv3167c. In addition, we discovered that the escape ofM. tuberculosisfrom its intracellular vacuole was greatly augmented by the presence of PDIM. The increased release ofM. tuberculosisinto the cytosol led to increased host cell necrosis. The discovery of a link between the cell wall lipid PDIM and a major pathogenesis pathway ofM. tuberculosisprovides important insights into the molecular mechanisms of host cell manipulation byM. tuberculosis.
Transcriptome Remodeling of
Acinetobacter baumannii
during Infection and Treatment
Authors: Wright Meredith S. , Jacobs Michael R. , Bonomo Robert A. , Adams Mark D.
Published: March 2017

Acinetobacter baumannii
is an increasingly common multidrug-resistant pathogen in health care settings. Although the genetic basis of antibiotic resistance mechanisms has been extensively studied, much less is known about how genetic variation contributes to other aspects of successful infections. Genetic changes that occur during host infection and treatment have the potential to remodel gene expression patterns related to resistance and pathogenesis. Longitudinal sets of multidrug-resistant
A. baumannii
isolates from eight patients were analyzed by RNA sequencing (RNA-seq) to identify differentially expressed genes and link them to genetic changes contributing to transcriptional variation at both within-patient and population levels. The number of differentially expressed genes among isolates from the same patient ranged from 26 (patient 588) to 145 (patient 475). Multiple patients had isolates with differential gene expression patterns related to mutations in the
pmrAB
and
adeRS
two-component regulatory system genes, as well as significant differences in genes related to antibiotic resistance, iron acquisition, amino acid metabolism, and surface-associated proteins. Population level analysis revealed 39 genetic regions with clade-specific differentially expressed genes, for which 19, 8, and 3 of these could be explained by insertion sequence mobilization, recombination-driven sequence variation, and intergenic mutations, respectively. Multiple types of mutations that arise during infection can significantly remodel the expression of genes that are known to be important in pathogenesis.

IMPORTANCE
Health care-associated multidrug-resistant
Acinetobacter baumannii
can cause persistent infections in patients, but bacterial cells must overcome host defenses and antibiotic therapies to do so. Genetic variation arises during host infection, and new mutations are often enriched in genes encoding transcriptional regulators, iron acquisition systems, and surface-associated structures. In this study, genetic variation was shown to result in transcriptome remodeling at the level of individual patients and across phylogenetic groups. Differentially expressed genes include those related to capsule modification, iron acquisition, type I pili, and antibiotic resistance. Population level transcriptional variation reflects genome dynamics over longer evolutionary time periods, and convergent transcriptional changes support the adaptive significance of these regions. Transcriptional changes can be attributed to multiple types of genomic change, but insertion sequence mobilization had a predominant effect. The transcriptional effects of mutations that arise during infection highlight the rapid adaptation of
A. baumannii
during host exposure.
Bilateral fixation of a periprosthetic intertrochanteric hip fracture below Birmingham hip resurfacing
Authors: Macdonald J , Pagoti R , Cusick L
Published: March 2017

This case report involves a 59-year-old woman with a traumatic right intertrochanteric hip fracture below a previous Birmingham hip resurfacing (BHR). This woman had almost an identical fracture on the left hip 3 years before which was treated with a proximal femoral locking compression plate. Of note periprosthetic fractures following hip resurfacing are usually subcapital and treated with a revision or conservative management. We present an unusual surgical problem that has occurred twice in the same patient and has been treated effectively on both occasions using proximal femoral plating. To the best of our knowledge, there have been no other reports of bilateral periprosthetic fractures being treated in this way.
The prognostic value of MRI in determining reinjury risk following acute hamstring injury: a systematic review
Authors: van Heumen Moniek , Tol Johannes L , de Vos Robert-Jan , Moen Maarten H , Weir Adam , Orchard John , Reurink Gustaaf
Published: March 2017

Background

A challenge for sports physicians is to estimate the risk of a hamstring re-injury, but the current evidence for MRI variables as a risk factor is unknown.

Objective

To systematically review the literature on the prognostic value of MRI findings at index injury and/or return to play for acute hamstring re-injuries.

Data sources

Databases of PubMed, Embase, MEDLINE, Scopus, CINAHL, Google Scholar, Web of Science, LILACS, SciELO, ScienceDirect, ProQuest, SPORTDiscus and Cochrane Library were searched until 20 June 2016.

Study eligibility criteria

Studies evaluating MRI as a prognostic tool for determining the risk of re-injury for athletes with acute hamstring injuries were eligible for inclusion.

Data analysis

Two authors independently screened the search results and assessed risk of bias using standardised criteria from a consensus statement. A best-evidence synthesis was used to identify the level of evidence. Post hoc analysis included correction for insufficient sample size.

Results

Of the 11 studies included, 7 had a low and 4 had a high risk of bias. No strong evidence for any MRI finding as a risk factor for hamstring re-injury was found. There was moderate evidence that intratendinous injuries were associated with increased re-injury risk. Post hoc analysis showed moderate evidence that injury to the biceps femoris was a moderate to strong risk factor for re-injury.

Conclusion

There is currently no strong evidence for any MRI finding in predicting hamstring re-injury risk. Intratendinous injuries and biceps femoris injuries showed moderate evidence for association with a higher re-injury risk.

Systematic review registration

Registration in the PROSPERO International prospective register of systematic reviews was performed prior to study initiation (registration number CRD42015024620).
Blood flow restriction training in clinical musculoskeletal rehabilitation: a systematic review and meta-analysis
Authors: Hughes Luke , Paton Bruce , Rosenblatt Ben , Gissane Conor , Patterson Stephen David
Published: March 2017

Background and objective

Low-load exercise training with blood flow restriction (BFR) can increase muscle strength and may offer an effective clinical musculoskeletal (MSK) rehabilitation tool. The aim of this review was to systematically analyse the evidence regarding the effectiveness of this novel training modality in clinical MSK rehabilitation.

Design

This is a systematic review and meta-analysis of peer-reviewed literature examining BFR training in clinical MSK rehabilitation (Research Registry; researchregistry91).

Data sources

A literature search was conducted across SPORTDiscus (EBSCO), PubMed and Science Direct databases, including the reference lists of relevant papers. Two independent reviewers extracted study characteristics and MSK and functional outcome measures. Study quality and reporting was assessed using the Tool for the assEssment of Study qualiTy and reporting in EXercise.

Eligibility

Search results were limited to exercise training studies investigating BFR training in clinical MSK rehabilitation, published in a scientific peer-reviewed journal in English.

Results

Twenty studies were eligible, including ACL reconstruction (n=3), knee osteoarthritis (n=3), older adults at risk of sarcopenia (n=13) and patients with sporadic inclusion body myositis (n=1). Analysis of pooled data indicated low-load BFR training had a moderate effect on increasing strength (Hedges’ g=0.523, 95% CI 0.263 to 0.784, p<0.001), but was less effective than heavy-load training (Hedges’ g=0.674, 95% CI 0.296 to 1.052, p<0.001).

Conclusion

Compared with low-load training, low-load BFR training is more effective, tolerable and therefore a potential clinical rehabilitation tool. There is a need for the development of an individualised approach to training prescription to minimise patient risk and increase effectiveness.
Calf muscle strain injuries in sport: a systematic review of risk factors for injury
Authors: Green Brady , Pizzari Tania
Published: March 2017

Objective

To systematically review the literature to identify risk factors for calf strain injury, and to direct future research into calf muscle injuries.

Design

Systematic review

Data sources

Database searches conducted for Medline, CINAHL, EMBASE, AMED, AUSPORT, SportDiscus, PEDro and Cochrane Library. Manual reference checks, ahead of press searches, citation tracking. From inception to June 2016.

Eligibility criteria for selecting studies

Studies evaluating and presenting data related to intrinsic or extrinsic risk factors for sustaining future calf injury.

Results

Ten studies were obtained for review. Subjects across football, Australian football, rugby union, basketball and triathlon were reported on, representing 5397 athletes and 518 calf/ lower leg muscle injuries. Best evidence synthesis highlights chronological age and previous history of calf strain are the strongest risk factors for future calf muscle injury. Previous lower limb injuries (hamstring, quadriceps, adductor, knee) show some limited evidence for an association. Numerous factors lack evidence of an association, including height, weight, gender and side dominance.

Summary/conclusion

Increasing age and previous calf strain injury are the most predictive of future calf injury. The overall paucity of evidence and the trend for studies of a high risk of bias show that further research needs to be undertaken.
Supporting the management of type 2 diabetes with pharmacist-led reviews: an observational analysis
Authors: Langran Tim , Nanda Nithya , Bataveljic Attia , Gonzalez-Durio Javier
Published: March 2017

Objective

Describe and assess the impact of a pharmacist-led patient review programme on the management and control of type 2 diabetes (T2D).

Design

Uncontrolled prospective cohort study with before and after intervention data collection.

Setting

General practices within NHS Slough Clinical Commissioning Group (CCG).

Participants

5910 patients with T2D.

Interventions

Pharmacists reviewed 5910 patients and worked with general practice teams to schedule any of the 9 key care processes recommended by the National Institute for Health and Care Excellence (NICE) that the patients were lacking, to optimise medication and to make other interventions such as providing lifestyle advice.

Main outcome measures

The proportion of patients receiving the NICE-recommended 9 key care processes and proportion of patients whose glycated haemoglobin (HbA1c), blood pressure (BP) or total cholesterol (TC) readings were over target before and after the intervention period.

Results

The proportion of patients receiving all of the NICE-recommended 9 key care processes increased from 46% at project outset in April 2013 to 58% on completion in April 2014 and the percentage of patients achieving HbA1c, BP and TC targets all increased (65% to 70%, 70% to 76%, 78% to 82%, respectively). Quality Outcomes Framework (QOF) data for Slough CCG showed the percentage of diabetic patients achieving target HbA1c, BP and TC readings increased from April 2013 to April 2014, but then diminished in the year after project completion.

Conclusions

The pharmacist-led review increased the number of key care processes administered and improved diabetic control during the year of programme delivery. The improvement abated during the year after, suggesting that such programmes should be ongoing rather than fixed term. The programme combined the strategic drive and project facilitation skills of Slough CCG, the general practice teams' knowledge of their patients and the clinical and information technology skills of an experienced pharmacist team.
Does early intervention improve outcomes in physiotherapy management of lumbar radicular syndrome? A mixed-methods study protocol
Authors: Reddington Michael , Walters Stephen J , Cohen Judith , Baxter Susan
Published: March 2017

Introduction

Lumbar radicular syndrome (LRS) can be a painful and debilitating condition. The optimum management strategies and their timing remain elusive despite extensive research. Surgery provides good short-term outcomes but has concomitant risks and costs. Physiotherapy is commonly practised for patients with LRS but its effects remain equivocal and there is a lack of consensus on the type, duration and timing of physiotherapy intervention. There is a lack of high-quality evidence into new and innovative management strategies and the timings of those strategies for LRS. This pilot trial is an essential preliminary to a definitive randomised controlled trial (RCT) assessing the effectiveness and cost-effectiveness of early physiotherapy intervention for patients with LRS. The study will test the protocol, the intervention, the use of outcome measures and the ability to set-up and run the trial to enable refinement of a future definitive RCT.

Methods and analysis

This is a mixed-methods study encompassing an external pilot RCT with integrated qualitative interviews with patients, clinicians and other key stakeholders. 80 patients will be recruited from primary care and randomised, after consent into 1 of 2 groups. Both groups will receive individually tailored, goal orientated physiotherapy. The usual care group will begin their physiotherapy 6 weeks after randomisation and the intervention group at 2 weeks after randomisation. Outcome measures will primarily be feasibility parameters including the ability to recruit and retain patients and to deliver the intervention. Data will be collected at baseline, and 6, 12 and 26 weeks following randomisation.

Ethics and dissemination

The study has received favourable ethical review from the East of Scotland Research Ethics Service (EoSRES) on the 20 August 2015 (15/ES/0130). Recruitment began on the 1 March 2016 and is expected to close in January 2017. Data collection is anticipated to be complete in July 2017. The study results will be made available to participants, clinicians involved in the study and the wider clinical community through publication in a peer reviewed journal and at conference presentations.

Trial registration number

ISRCTN: 25018352, Pre-results; Clinical Trials.Gov:NCT02618278Document version V1.1 23.9.2016.
Restrictive versus liberal fluid therapy in major abdominal surgery (RELIEF): rationale and design for a multicentre randomised trial
Authors: Myles Paul , Bellomo Rinaldo , Corcoran Tomas , Forbes Andrew , Wallace Sophie , Peyton Philip , Christophi Chris , Story David , Leslie Kate , Serpell Jonathan , McGuinness Shay , Parke Rachel
Published: March 2017

Introduction

The optimal intravenous fluid regimen for patients undergoing major abdominal surgery is unclear. However, results from many small studies suggest a restrictive regimen may lead to better outcomes. A large, definitive clinical trial evaluating perioperative fluid replacement in major abdominal surgery, therefore, is required.

Methods/analysis

We designed a pragmatic, multicentre, randomised, controlled trial (the RELIEF trial). A total of 3000 patients were enrolled in this study and randomly allocated to a restrictive or liberal fluid regimen in a 1:1 ratio, stratified by centre and planned critical care admission. The expected fluid volumes in the first 24 hour from the start of surgery in restrictive and liberal groups were ≤3.0 L and ≥5.4 L, respectively. Patient enrolment is complete, and follow-up for the primary end point is ongoing. The primary outcome is disability-free survival at 1 year after surgery, with disability defined as a persistent (at least 6 months) reduction in functional status using the 12-item version of the World Health Organisation Disability Assessment Schedule.

Ethics/dissemination

The RELIEF trial has been approved by the responsible ethics committees of all participating sites. Participant recruitment began in March 2013 and was completed in August 2016, and 1-year follow-up will conclude in August 2017. Publication of the results of the RELIEF trial is anticipated in early 2018.

Trial registration number

ClinicalTrials.gov identifierNCT01424150.