bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of marital status and colorectal cancer screening participation in the USA
Authors: El‐Haddad B. , Dong F. , Kallail K. J. , Hines R. B. , Ablah E.
Published: February 2015

Aim

In the USA, for both men and women, colorectal cancer (CRC) ranks third in incidence and second in mortality. Despite evidence that it decreases mortality, CRC screening in the USA remains under‐utilized. Some European studies have suggested that marital status affects participation in CRC screening, but the effect of marital status on CRC screening participation in the USA is unknown. In this study, the aim was to compare CRC screening participation rates among married and unmarried couples, separated, widowed, never married and divorced adults living in the USA.

Method

This was a retrospective data analysis of the 2010 Behavioural Risk Factor Surveillance System survey. The population studied included 239 300 participants, aged 50–75 years, who completed the 2010 survey. Logistic regression analysis was conducted to assess the association between adherence with CRC screening guidelines and marital status while accounting for survey stratum/weight and covariates.

Results

Individuals who were divorced or separated, never married or widowed had decreased odds of adherence with CRC screening guidelines compared with individuals who were married and unmarried couples.

Conclusion

In this study, individuals living in the USA who were married and unmarried couples had increased odds of undergoing CRC screening compared to individuals in other marital status groups. Public health interventions are needed to promote CRC screening participation in these other groups.
Global and local evolutionary and ecological distinctiveness of terrestrial mammals: identifying priorities across scales
Authors: Hidasi‐Neto José , Loyola Rafael , Cianciaruso Marcus V.
Published: February 2015

Aim

Species' ecological traits and evolutionary relatedness have gained attention in the scientific community for their important roles in the functioning and stability of ecosystems. However, conservation science is in urgent need of methods that integrate both ecological and evolutionary components of biodiversity into conservation strategies for threatened species. Here, we propose an approach to identify and locate ‘ecologically and evolutionarily distinct and globally endangered’ species (EcoEDGE) at broad and fine geographical scales.

Location

Global.

Methods

We used phylogeny and life‐history traits to calculate evolutionary and ecological distinctiveness values of terrestrial mammals. We combined these values into one measure, EcoEDGE, which also considers species' threat status. Then, we correlated values of ecological and evolutionary distinctiveness (ED) and mapped the geographical distribution of species to locate regions with high number of mammals with great EcoEDGE scores. We also identified and located areas with high number of mammals that are highly distinct across most local assemblages in which they occur.

Results

Ecological and ED tended to be complementary to each other rather than redundant. Evolutionarily distinct threatened species were mostly concentrated in the tropics, while ecologically distinct threatened species were distributed across tropical and temperate regions. In addition, both ecologically and evolutionarily distinct threatened species overlapped their distributions with biodiversity hotspots, including the Atlantic forest, the Cerrado, Indo‐Burma and Sundaland. Mammals with great EcoEDGE scores were concentrated in the tropics, but because they retained patterns from ecologically distinct species, their distribution stretched into temperate regions. Moreover, Africa, Australia and Indo‐Malayan regions held a great number of mammals with unique ecological and evolutionary roles in the local assemblages where they occur.

Main conclusions

Ecologically and evolutionarily distinct and globally endangered builds upon existing strategies that include ecological traits into a species‐focused prioritization approach and, thus, further informs conservation of ecosystem processes and services at multiple geographical scales.
A histological investigation of Oriental beech wood decayed by Pleurotus ostreatus and Trametes versicolor
Authors: Bari E. , Schmidt O. , Oladi R.
Published: February 2015

Chemical, light and electron microscopic studies were carried out on wood of Oriental beech (Fagus orientalis Lipsky) decayed by the white‐rot fungi Pleurotus ostreatus and Trametes versicolor for 30, 60 and 120 days according to the modified European standard EN 113. Mass loss as well as lignin, cellulose and carbohydrate content were determined before and after fungal attack. There were no significant differences of wood mass loss and chemical composition between both fungi at the end of incubation. After each incubation period, small specimens were stained for microscopic studies. The micromorphology of fungal cell wall degradation was rather similar for both fungi. Both decreased the cell wall thickness to the same extent. The accumulation of hyphae as well as the rupture of cell walls was also similar. The occurrence of hyphae, cavities in the pits and vessel walls followed nearly the same patterns. The parenchyma cells were completely destroyed. Altogether, both fungi produced a simultaneous white rot in Oriental beech wood.
Hemispheric lateralization in top‐down attention during spatial relation processing: a Granger causal model approach
Authors: Falasca N. W. , D'Ascenzo S. , Di Domenico A. , Onofrj M. , Tommasi L. , Laeng B. , Franciotti R.
Published: February 2015

Magnetoencephalography was recorded during a matching‐to‐sample plus cueing paradigm, in which participants judged the occurrence of changes in either categorical (CAT) or coordinate (COO) spatial relations. Previously, parietal and frontal lobes were identified as key areas in processing spatial relations and it was shown that each hemisphere was differently involved and modulated by the scope of the attention window (e.g. a large and small cue). In this study, Granger analysis highlighted the patterns of causality among involved brain areas – the direction of information transfer ran from the frontal to the visual cortex in the right hemisphere, whereas it ran in the opposite direction in the left side. Thus, the right frontal area seems to exert top‐down influence, supporting the idea that, in this task, top‐down signals are selectively related to the right side. Additionally, for CAT change preceded by a small cue, the right frontal gyrus was not involved in the information transfer, indicating a selective specialization of the left hemisphere for this condition. The present findings strengthen the conclusion of the presence of a remarkable hemispheric specialization for spatial relation processing and illustrate the complex interactions between the lateralized parts of the neural network. Moreover, they illustrate how focusing attention over large or small regions of the visual field engages these lateralized networks differently, particularly in the frontal regions of each hemisphere, consistent with the theory that spatial relation judgements require a fronto‐parietal network in the left hemisphere for categorical relations and on the right hemisphere for coordinate spatial processing.
Modelling the influence of predicted future climate change on the risk of wind damage within New Zealand's planted forests
Authors: Moore John R. , Watt Michael S.
Published: February 2015

Wind is the major abiotic disturbance in New Zealand's planted forests, but little is known about how the risk of wind damage may be affected by future climate change. We linked a mechanistic wind damage model (ForestGALES) to an empirical growth model for radiata pine (Pinus radiata D. Don) and a process‐based growth model (cenw) to predict the risk of wind damage under different future emissions scenarios and assumptions about the future wind climate. The cenw model was used to estimate site productivity for constant CO2 concentration at 1990 values and for assumed increases in CO2 concentration from current values to those expected during 2040 and 2090 under the B1 (low), A1B (mid‐range) and A2 (high) emission scenarios. Stand development was modelled for different levels of site productivity, contrasting silvicultural regimes and sites across New Zealand. The risk of wind damage was predicted for each regime and emission scenario combination using the ForestGALES model. The sensitivity to changes in the intensity of the future wind climate was also examined. Results showed that increased tree growth rates under the different emissions scenarios had the greatest impact on the risk of wind damage. The increase in risk was greatest for stands growing at high stand density under the A2 emissions scenario with increased CO2 concentration. The increased productivity under this scenario resulted in increased tree height, without a corresponding increase in diameter, leading to more slender trees that were predicted to be at greater risk from wind damage. The risk of wind damage was further increased by the modest increases in the extreme wind climate that are predicted to occur. These results have implications for the development of silvicultural regimes that are resilient to climate change and also indicate that future productivity gains may be offset by greater losses from disturbances.
Evaluating a hand‐held crop‐measuring device for estimating the herbage biomass, leaf area index and crude protein content in an Italian ryegrass field
Authors: Lim Jihyun , Kawamura Kensuke , Lee Hyo‐Jin , Yoshitoshi Rena , Kurokawa Yuzo , Tsumiyama Yoshimasa , Watanabe Nariyasu
Published: February 2015

The objective of this study is to evaluate the ability of a newly developed hand‐held crop‐measuring device and vegetation indices (VIs) to estimate the herbage biomass (BM), leaf area index (LAI) and forage crude protein mass (CPmass) in an Italian ryegrass (Lolium multiflorum Lam.) field, Japan. The device uses bi‐directional passive sensors (550, 650 and 880 nm) upward and downward to overcome the major drawback of optical remote sensing as influenced by weather conditions. The canopy reflectance and plant sample data were collected 11 times during two winter growing seasons in 2010–11 and 2011–12. Seven VIs were compared to estimate the forage parameters in the normal and logarithmic forms. The predictive ability of the VIs was assessed by the cross‐validated coefficient of determination (R2cv) and the residual prediction (RPD) values. Acceptable RPD values (>1.5) were found in most of the log‐transformed forage parameters with all of the VIs but not in most of the normal‐form. The highest R2cv and RPD were obtained in the normalized difference vegetation index (NDVI) for the ln BM (R2cv = 0.76, RPD = 2.04) and ln LAI (R2cv = 0.80, RPD = 2.25), and the highest modified soil‐adjusted vegetation index (MSAVI) was obtained for the ln CPmass (R2cv = 0.78, RPD = 2.16). By evaluating the limitation of NDVI or MSAVI sensitivity with ranges of cumulative data, the log‐transformed forage parameters showed good R2cv values in the ln BM (0.76–0.79), ln LAI (0.80–0.84) and ln CPmass (0.71–0.84) with acceptable RPD values throughout most of the range, whereas in the normal‐form, the NDVI or MSAVI was saturated at moderate‐high BM, LAI or CPmass, causing the R2cv and RPD values to decrease with increasing plant parameters. These results suggest that this device is applicable in log‐transformed BM, LAI and CPmass throughout the growing season without cloud effect.
Analysis of miRNA expression patterns in human and mouse hepatocellular carcinoma cells
Authors: Baek Sinhwa , Cho Kyung Joo , Ju Hye‐Lim , Moon Hyuk , Choi Sung Hoon , Chung Sook In , Park Jun Yong , Choi Ki Hong , Kim Do Young , Ahn Sang Hoon , Han Kwang‐Hyub , Ro Simon Weonsang
Published: February 2015

Aim

Hepatocellular carcinoma (HCC), one of the most common malignancies in adults displays aberrant miRNA expression during its pathogenesis. We assessed expression of miRNA in surgically resected human HCC of an early stage and murine HCC with a high malignancy in order to find miRNA overexpressed in HCC regardless of tumor stage and underlying etiology. Further, the role of the deregulated miRNA in HCC pathogenesis was investigated.

Methods

miRNA were isolated from HCC tissues and surrounding non‐tumorous tissues from HCC patients and a murine transgenic model of HCC. A quantitative reverse transcription polymerase chain reaction was performed to determine expression levels of miRNA. Human HCC cell lines stably expressing individual miRNA were generated to investigate the biological function of overexpressed miRNA.

Results

We found that levels of miR‐221, ‐181b‐1, ‐155‐5p, ‐25 and ‐17‐5p were significantly upregulated in both human and murine HCC regardless of tumor stage, underlying etiology or the presence of fibrosis. Using HCC cell lines stably expressing respective miRNA, we found that miR‐221 increased the proliferation of hepatoma cells, while miR‐17‐5p induced cell migration.

Conclusion

We identified miRNA that are consistently upregulated in HCC. The overexpressed miRNA could potentially be used as a bona fide biomarker for HCC.
Cytokine and lipid mediator networks in tuberculosis
Authors: Mayer‐Barber Katrin D. , Sher Alan
Published: February 2015

A major approach for immunologic intervention in tuberculosis involves redirecting the outcome of the host immune response from the induction of disease to pathogen control. Cytokines and lipid mediators known as eicosanoids play key roles in regulating this balance and as such represent important targets for immunologic intervention. While the evidence for cytokine/eicosanoid function derives largely from the investigation of murine and zebrafish experimental infection models, clinical studies have confirmed the existence of many of the same pathways in tuberculosis patients. Here, we summarize new data that reveal important intersections between the cytokine and eicosanoid networks in the host response to mycobacteria and discuss how targeting this crosstalk can promote resistance to lethal Mycobacterium tuberculosis infection. This approach could lead to new host‐directed therapies to be used either as an adjunct for improving the efficacy of standard antibiotic treatment or for the management of drug‐resistant infections.
Release of mycobacterial antigens
Authors: Majlessi Laleh , Prados‐Rosales Rafael , Casadevall Arturo , Brosch Roland
Published: February 2015

Mycobacterium tuberculosis has evolved from a Mycobacterium canettii‐like progenitor pool into one of the most successful and widespread human pathogens. The pathogenicity of M. tuberculosis is linked to its ability to secrete/export/release selected mycobacterial proteins, and it is also established that active release of mycobacterial antigens is a prerequisite for strong immune recognition. Recent research has enabled mycobacterial secretion systems and vesicle‐based release of mycobacterial antigens to be elucidated, which together with host‐related specificities constitute key variables that determine the outcome of infection. Here, we discuss recently discovered, novel aspects on the nature and the regulation of antigen release of the tuberculosis agent with particular emphasis on the biological characterization of mycobacteria‐specific ESX/type VII secretion systems and their secreted proteins, belonging to the Esx, PE, and PPE categories. The importance of specific mycobacterial antigen release is probably best exemplified by the striking differences observed between the cellular events during infection with the ESX‐1‐deficient, attenuated Mycobacterium bovis BCG compared to the virulent M. tuberculosis, which are clearly important for design of more specific diagnostics and more efficient vaccines.
Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses
Authors: Lenaerts Anne , Barry Clifton E. , Dartois Véronique
Published: February 2015

Tuberculosis (TB) lesions are extremely complex and dynamic. Here, we review the multiple types and fates of pulmonary lesions that form following infection by Mycobacterium tuberculosis and the impact of this spatial and temporal heterogeneity on the bacteria they harbor. The diverse immunopathology of granulomas and cavities generates a plethora of microenvironments to which M. tuberculosis bacilli must adapt. This in turn affects the replication, metabolism, and relative density of bacterial subpopulations, and consequently their respective susceptibility to chemotherapy. We outline recent developments that support a paradigm shift in our understanding of lesion progression. The simple model according to which lesions within a single individual react similarly to the systemic immune response no longer prevails. Host‐pathogen interactions within lesions are a dynamic process, driven by subtle and local differences in signaling pathways, resulting in diverging trajectories of lesions within a single host. The spectrum of TB lesions is a continuum with a large overlap in the lesion types found in latently infected and active TB patients. We hope this overview will guide TB researchers in the design, choice of read‐outs, and interpretation of future studies in the search for predictive biomarkers and novel therapies.
CD1 and mycobacterial lipids activate human T cells
Authors: Van Rhijn Ildiko , Moody D. Branch
Published: February 2015

For decades, proteins were thought to be the sole or at least the dominant source of antigens for T cells. Studies in the 1990s demonstrated that CD1 proteins and mycobacterial lipids form specific targets of human αβ T cells. The molecular basis by which T‐cell receptors (TCRs) recognize CD1‐lipid complexes is now well understood. Many types of mycobacterial lipids function as antigens in the CD1 system, and new studies done with CD1 tetramers identify T‐cell populations in the blood of tuberculosis patients. In human populations, a fundamental difference between the CD1 and major histocompatibility complex systems is that all humans express nearly identical CD1 proteins. Correspondingly, human CD1 responsive T cells show evidence of conserved TCRs. In addition to natural killer T cells and mucosal‐associated invariant T (MAIT cells), conserved TCRs define other subsets of human T cells, including germline‐encoded mycolyl‐reactive (GEM) T cells. The simple immunogenetics of the CD1 system and new investigative tools to measure T‐cell responses in humans now creates a situation in which known lipid antigens can be developed as immunodiagnostic and immunotherapeutic reagents for tuberculosis disease.
New tricks for old dogs: countering antibiotic resistance in tuberculosis with host‐directed therapeutics
Authors: Hawn Thomas R. , Shah Javeed A. , Kalman Daniel
Published: February 2015

Despite the availability of Mycobacterium tuberculosis (Mtb) drugs for over 50 years, tuberculosis (TB) remains at pandemic levels. New drugs are urgently needed for resistant strains, shortening duration of treatment, and targeting different stages of the disease, especially for treatment during human immunodeficiency virus co‐infection. One solution to the conundrum that antibiotics kill the bacillus yet select for resistance is to target the host rather than the pathogen. Here, we discuss recent progress in so‐called ‘host‐directed therapeutics’ (HDTs), focusing on two general mechanistic strategies: (i) HDTs that disrupt Mtb pathogenesis in macrophages and (ii) immunomodulatory HDTs that facilitate protective immune responses that kill Mtb or reduce deleterious responses that exacerbate disease. HDTs hold significant promise as adjunctive therapies in that they are less likely to engender resistance, will likely have efficacy against antibiotic‐resistant strains, and may have activity against non‐replicating Mtb. However, TB is a complex and variegated disease, and human populations exhibit significant diversity in their immune responses to it, which presents a complicated landscape for HDTs to navigate. Nevertheless, we suggest that a detailed mechanistic understanding of drug action, together with careful selection of disease stage targets and dosing strategies may overcome such limitations and allow the development of HDTs as effective adjunctive treatment options for TB.
Mycobacterial genes essential for the pathogen's survival in the host
Authors: Ehrt Sabine , Rhee Kyu , Schnappinger Dirk
Published: February 2015

Mycobacterium tuberculosis (Mtb) has evolved within the human immune system as both host and reservoir. The study of genes required for its growth and persistence in vivo thus offers linked insights into its pathogenicity and host immunity. Studies of Mtb mutants have implicated metabolic adaptation (consisting of carbon, nitrogen, vitamin, and cofactor metabolism), intrabacterial pH homeostasis, and defense against reactive oxygen and reactive nitrogen species, as key determinants of its pathogenicity. However, the mechanisms of host immunity are complex and often combinatorial. Growing evidence has thus begun to reveal that the determinants of Mtb's pathogenicity may serve a broader and more complex array of functions than the isolated experimental settings in which they were initially found. Here, we review select examples, which exemplify this complexity, highlighting the distinct phases of Mtb's life cycle and the diverse microenvironments encountered therein.
Co‐evolution of Mycobacterium tuberculosis and Homo sapiens
Authors: Brites Daniela , Gagneux Sebastien
Published: February 2015

The causative agent of human tuberculosis (TB), Mycobacterium tuberculosis, is an obligate pathogen that evolved to exclusively persist in human populations. For M. tuberculosis to transmit from person to person, it has to cause pulmonary disease. Therefore, M. tuberculosis virulence has likely been a significant determinant of the association between M. tuberculosis and humans. Indeed, the evolutionary success of some M. tuberculosis genotypes seems at least partially attributable to their increased virulence. The latter possibly evolved as a consequence of human demographic expansions. If co‐evolution occurred, humans would have counteracted to minimize the deleterious effects of M. tuberculosis virulence. The fact that human resistance to infection has a strong genetic basis is a likely consequence of such a counter‐response. The genetic architecture underlying human resistance to M. tuberculosis remains largely elusive. However, interactions between human genetic polymorphisms and M. tuberculosis genotypes have been reported. Such interactions are consistent with local adaptation and allow for a better understanding of protective immunity in TB. Future ‘genome‐to‐genome’ studies, in which locally associated human and M. tuberculosis genotypes are interrogated in conjunction, will help identify new protective antigens for the development of better TB vaccines.
Macrophage defense mechanisms against intracellular bacteria
Authors: Weiss Günter , Schaible Ulrich E.
Published: February 2015

Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and eliminate intracellular M. tuberculosis decides whether a patient initially becomes infected or not. However, when the infection becomes chronic or even latent (as in the case of TB) despite development of specific immune activation, phagocytes have also important effector functions. Macrophages have evolved a myriad of defense strategies to combat infection with intracellular bacteria such as M. tuberculosis. These include induction of toxic anti‐microbial effectors such as nitric oxide and reactive oxygen intermediates, the stimulation of microbe intoxication mechanisms via acidification or metal accumulation in the phagolysosome, the restriction of the microbe's access to essential nutrients such as iron, fatty acids, or amino acids, the production of anti‐microbial peptides and cytokines, along with induction of autophagy and efferocytosis to eliminate the pathogen. On the other hand, M. tuberculosis, as a prime example of a well‐adapted facultative intracellular bacterium, has learned during evolution to counter‐balance the host's immune defense strategies to secure survival or multiplication within this otherwise hostile environment. This review provides an overview of innate immune defense of macrophages directed against intracellular bacteria with a focus on M. tuberculosis. Gaining more insights and knowledge into this complex network of host‐pathogen interaction will identify novel target sites of intervention to successfully clear infection at a time of rapidly emerging multi‐resistance of M. tuberculosis against conventional antibiotics.
Immunoevasion and immunosuppression of the macrophage by Mycobacterium tuberculosis
Authors: Hmama Zakaria , Peña‐Díaz Sandra , Joseph Sunil , Av‐Gay Yossef
Published: February 2015

By virtue of their position at the crossroads between the innate and adaptive immune response, macrophages play an essential role in the control of bacterial infections. Paradoxically, macrophages serve as the natural habitat to Mycobacterium tuberculosis (Mtb). Mtb subverts the macrophage's mechanisms of intracellular killing and antigen presentation, leading ultimately to the development of tuberculosis (TB) disease. Here, we describe mechanisms of Mtb uptake by the macrophage and address key macrophage functions that are targeted by Mtb‐specific effector molecules enabling this pathogen to circumvent host immune response. The macrophage functions described in this review include fusion between phagosomes and lysosomes, production of reactive oxygen and nitrogen species, antigen presentation and major histocompatibility complex class II expression and trafficking, as well as autophagy and apoptosis. All these are Mtb‐targeted key cellular pathways, normally working in concert in the macrophage to recognize, respond, and activate ‘proper’ immune responses. We further analyze and discuss major molecular interactions between Mtb virulence factors and key macrophage proteins and provide implications for vaccine and drug development.
The human immune response to tuberculosis and its treatment: a view from the blood
Authors: Cliff Jacqueline M. , Kaufmann Stefan H. E. , McShane Helen , van Helden Paul , O'Garra Anne
Published: February 2015

The immune response upon infection with the pathogen Mycobacterium tuberculosis is poorly understood, hampering the discovery of new treatments and the improvements in diagnosis. In the last years, a blood transcriptional signature in tuberculosis has provided knowledge on the immune response occurring during active tuberculosis disease. This signature was absent in the majority of asymptomatic individuals who are latently infected with M. tuberculosis (referred to as latent). Using modular and pathway analyses of the complex data has shown, now in multiple studies, that the signature of active tuberculosis is dominated by overexpression of interferon‐inducible genes (consisting of both type I and type II interferon signaling), myeloid genes, and inflammatory genes. There is also downregulation of genes encoding B and T‐cell function. The blood signature of tuberculosis correlates with the extent of radiographic disease and is diminished upon effective treatment suggesting the possibility of new improved strategies to support diagnostic assays and methods for drug treatment monitoring. The signature suggested a previously under‐appreciated role for type I interferons in development of active tuberculosis disease, and numerous mechanisms have now been uncovered to explain how type I interferon impedes the protective response to M. tuberculosis infection.
MR1‐restricted mucosal associated invariant T (MAIT) cells in the immune response to Mycobacterium tuberculosis
Authors: Gold Marielle C. , Napier Ruth J. , Lewinsohn David M.
Published: February 2015

The intracellular pathogen Mycobacterium tuberculosis (Mtb) and its human host have long co‐evolved. Although the host cellular immune response is critical to the control of the bacterium information on the specific contribution of different immune cell subsets in humans is incomplete. Mucosal associated invariant T (MAIT) cells are a prevalent and unique T‐cell population in humans with the capacity to detect intracellular infection with bacteria including Mtb. MAIT cells detect bacterially derived metabolites presented by the evolutionarily conserved major histocompatibility complex‐like molecule MR1. Here, we review recent advances in our understanding of this T‐cell subset and address the potential roles for MR1‐restricted T cells in the control, diagnosis, and therapy of tuberculosis.
Inherited and acquired immunodeficiencies underlying tuberculosis in childhood
Authors: Boisson‐Dupuis Stéphanie , Bustamante Jacinta , El‐Baghdadi Jamila , Camcioglu Yildiz , Parvaneh Nima , El Azbaoui Safaa , Agader Aomar , Hassani Amal , El Hafidi Naima , Mrani Nidal Alaoui , Jouhadi Zineb , Ailal Fatima , Najib Jilali , Reisli Ismail , Zamani Adil , Yosunkaya Sebnem , Gulle‐Girit Saniye , Yildiran Alisan , Cipe Funda Erol , Torun Selda Hancerli , Metin Ayse , Atikan Basak Yildiz , Hatipoglu Nevin , Aydogmus Cigdem , Kilic Sara Sebnem , Dogu Figen , Karaca Neslihan , Aksu Guzide , Kutukculer Necil , Keser‐Emiroglu Melike , Somer Ayper , Tanir Gonul , Aytekin Caner , Adimi Parisa , Mahdaviani Seyed Alireza , Mamishi Setareh , Bousfiha Aziz , Sanal Ozden , Mansouri Davood , Casanova Jean‐Laurent , Abel Laurent
Published: February 2015

Tuberculosis (TB), caused byMycobacterium tuberculosis(M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life‐threatening primaryTBof childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not onlyM.tbbut also weakly virulent mycobacteria, such asBCGvaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer thanTB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhoodTB, as illustrated by the discovery of single‐gene inborn errors ofIFN‐γ immunity underlying severe cases ofTB. Novel findings are expected from ongoing and future human genetic studies of childhoodTBin countries that combine a high proportion of consanguineous marriages, a high incidence ofTB, and an excellent clinical care, such as Iran, Morocco, and Turkey.
Adventures within the speckled band: heterogeneity, angiogenesis, and balanced inflammation in the tuberculous granuloma
Authors: Matty Molly A. , Roca Francisco J. , Cronan Mark R. , Tobin David M.
Published: February 2015

Recent work in a variety of animal models, including mice, zebrafish, and macaques, as well as in humans, has led to a reassessment of several tenets of mycobacterial infection. In this review, we describe new findings about the composition and dynamics of the tuberculous granuloma, the central host structure in mycobacterial infection, as well as inflammatory mediators that drive a successful anti‐microbial response on one hand and pathological inflammation on the other. We highlight granuloma heterogeneity that emerges in the context of infection, the functional consequences of angiogenesis in tuberculous granulomas, and data that balanced inflammation in humans, with a central role for tumor necrosis factor, appears to play a key role in optimal defense against mycobacterial infection. These findings have suggested new and specific host‐directed therapies that await further clinical exploration.
TB drug development: immunology at the table
Authors: Nathan Carl , Barry Clifton E.
Published: February 2015

Our understanding of the host‐pathogen relationship in tuberculosis (TB) can help guide drug discovery in at least two ways. First, the recognition that host immunopathology affects lesional TB drug distribution means that pharmacokinetic evaluation of drug candidates needs to move beyond measurements of drug levels in blood, whole lungs, or alveolar epithelial lining fluid to include measurements in specific types of lesions. Second, by restricting the replication of M. tuberculosis (Mtb) subpopulations in latent TB infection and in active disease, the host immune response puts Mtb into a state associated with phenotypic tolerance to TB drugs selected for their activity against replicating Mtb. This has spurred a major effort to conduct high throughput screens in vitro for compounds that can kill Mtb when it is replicating slowly if at all. Each condition used in vitro to slow Mtb's replication and thereby model the phenotypically drug‐tolerant state has advantages and disadvantages. Lead candidates emerging from such in vitro studies face daunting challenges in the design of proof‐of‐concept studies in animal models. Moreover, some non‐replicating subpopulations of Mtb fail to resume replication when plated on agar, although their viability is demonstrable by other means. There is as yet no widely replicated assay in which to screen compounds for their ability to kill this ‘viable but non‐culturable’ subpopulation. Despite these hurdles, drugs that can kill slowly replicating or non‐replicating Mtb may offer our best hope for treatment‐shortening combination chemotherapy of TB.
Differences in soil characteristics between field and forest may influence the distribution of an invasive earthworm
Authors: Ransom Tami S. , Billak Brittany J.
Published: February 2015

In northern North America, invasive earthworms (including the nightcrawler Lumbricus terrestris) have been dispersing from points of introduction and dramatically affecting soil structure, soil food webs, and forest floor dynamics. However, little is known about the factors influencing the local distribution of invasive earthworms south of the Wisconsinan glaciation. Earthworms were sampled at suspected sites of introduction near Mountain Lake Biological Field Station, Virginia, USA. The density of invasive earthworms decreased as distance from suspected sites of introduction increased; native earthworms displayed the opposite relationship. However, the distance that L. terrestris was found into the forest was less than expected given dispersal rates calculated from more northern invasions. We also found correlations among population densities of L. terrestris and physical–chemical properties of the soil, and differences between field and forest soils in terms of temperature, moisture, and soil chemical properties. We conducted two experiments to analyze some factors possibly responsible for the observed distribution: (1) temperature and moisture, and (2) soil type (field vs. forest) and food resources. Our results suggest that L. terrestris may not disperse as far into forested habitats of the Southern Appalachians compared to northern forests due to local physical‐chemical soil characteristics.
An exploratory study to identify risk factors for the development of capecitabine‐induced Palmar Plantar Erythrodysesthesia (PPE)
Authors: Law Annie , Dyson Sue , Anthony Denis
Published: February 2015

Aims

To identify pre‐treatment risk factors for the development of Palmar Plantar Erythrodysesthesia in participants receiving capecitabine monotherapy. Specifically the hypothesis that avoidance of activities that cause friction and pressure cause Palmar Plantar Erythrodysesthesia was tested.

Background

Previous literature showed contradictory evidence on the subject of predictors of chemotherapy‐induced Palmar Plantar Erythrodysesthesia. There is a lack of empirical evidence to support the theory that Palmar Plantar Erythrodysesthesia is caused by damage to the microcapillaries due to everyday activities that cause friction or pressure to the hands or feet.

Design

Prospective epidemiological study of risk factors.

Methods

Prospective data collection. All patients prior to commencing capecitabine monotherapy between 11 June 2009–31 December 2010, were offered recruitment into the study and followed up for six cycles of treatment (n = 174). Data were collected during semi‐structured interviews, from participants' diaries, physical examination of the hands and feet and review of notes. Data relating to activities that cause friction, pressure or heat were collected.

Data were analysed using bivariate (chi‐square and independent groups Student'st) tests where each independent variable was analysed against Palmar Plantar Erythrodysesthesia.

Results

The only variables that were associated with an increased risk of Palmar Plantar Erythrodysesthesia were a tendency to have warm hands and pre‐existing inflammatory disease.

Conclusions

This study gives no support for the hypothesis that avoidance of activities that cause friction and pressure cause Palmar Plantar Erythrodysesthesia.
Predictors of engagement in postpartum weight self‐management behaviours in the first 12 weeks after birth
Authors: Ohlendorf Jennifer M. , Weiss Marianne E. , Oswald Debra
Published: February 2015

Aim

To explore factors that influence postpartum weight self‐management behaviours. Transitions Theory and the Integrated Theory of Health Behaviour Change guided selection of variables. Transition conditions, level of patient activation and social facilitation were examined for association with postpartum weight self‐management behaviours.

Background

Retention of pregnancy weight increases risk of overweight and obesity later in life. Little is known about what women do to self‐manage return to pre‐pregnant weight and how providers can influence their behaviours.

Design

Prospective, longitudinal, correlational.

Methods

Data collection occurred from March through October, 2013. One hundred and twenty‐four women completed surveys during postpartum hospitalization; telephone interviews were completed by 91 women at 6 weeks and 66 women at 12 weeks. Standard and hierarchical multiple regression methods were used for analyses.

Results

Transition difficulty was negatively associated with patient activation and immediate postbirth patient activation was positively associated with eating behaviours at 6 weeks, eating behaviours at 12 weeks and physical activity at 12 weeks. Social support and social influence were not significant predictors in the regression models.

Conclusion

Patients experiencing a difficult postpartum transition have lower activation levels; those less activated are less probably to engage in weight self‐management behaviours in the 12 weeks following their baby's birth. Patient activation level should be considered in tailoring promotion of healthy postpartum weight management.
The regulation of connective tissue growth factor expression influences the viability of human trabecular meshwork cells
Authors: Kuespert Sabrina , Junglas Benjamin , Braunger Barbara M. , Tamm Ernst R. , Fuchshofer Rudolf
Published: February 2015

Connective tissue growth factor (CTGF) induces extracellular matrix (ECM) synthesis and contractility in human trabecular meshwork (HTM) cells. Both processes are involved in the pathogenesis of primary open‐angle glaucoma. To date, little is known about regulation and function of CTGF expression in the trabecular meshwork (TM). Therefore, we analysed the effects of different aqueous humour proteins and stressors on CTGF expression in HTM cells. HTM cells from three different donors were treated with endothelin‐1, insulin‐like growth factor (IGF)‐1, angiotensin‐II, H2O2 and heat shock and were analysed by immunohistochemistry, real‐time RT‐PCR and Western blotting. Viability after H2O2 treatment was measured in CTGF silenced HTM‐N cells and their controls. Latrunculin A reduced expression of CTGF by about 50% compared to untreated HTM cells, whereas endothelin‐1, IGF‐1, angiotensin‐II, heat shock and oxidative stress led to a significant increase. Silencing of CTGF resulted in a delayed expression of αB‐crystallin and in reduced cell viability in comparison to the controls after oxidative stress. Conversely, CTGF treatment led to a higher cell viability rate after H2O2 treatment. CTGF expression is induced by factors that have been linked to glaucoma. An increased level of CTGF appears to protect TM cells against damage induced by stress. The beneficial effect of CTGF for viability of TM cells is likely associated with the effects on increased ECM synthesis and higher contractility of the TM, thereby contributing to reduced aqueous humour outflow facility causing increased intraocular pressure.
DICER1 regulated let‐7 expression levels in p53‐induced cancer repression requires cyclin D1
Authors: Sun Xin , Tang Shou‐Ching , Xu Chongwen , Wang Chenguang , Qin Sida , Du Ning , Liu Jian , Zhang Yiwen , Li Xiang , Luo Gang , Zhou Jie , Xu Fei , Ren Hong
Published: February 2015

Let‐7 miRNAs act as tumour suppressors by directly binding to the 3′UTRs of downstream gene products. The regulatory role of let‐7 in downstream gene expression has gained much interest in the cancer research community, as it controls multiple biological functions and determines cell fates. For example, one target of the let‐7 family is cyclin D1, which promotes G0/S cell cycle progression and oncogenesis, was correlated with endoribonuclease DICER1, another target of let‐7. Down‐regulated let‐7 has been identified in many types of tumours, suggesting a feedback loop may exist between let‐7 and cyclin D1. A potential player in the proposed feedback relationship is Dicer, a central regulator of miRNA expression through sequence‐specific silencing. We first identified that DICER1 is the key downstream gene for cyclin D1‐induced let‐7 expression. In addition, we found that let‐7 miRNAs expression decreased because of the p53‐induced cell death response, with deregulated cyclin D1. Our results also showed that cyclin D1 is required for Nutlin‐3 and TAX‐induced let‐7 expression in cancer repression and the cell death response. For the first time, we provide evidence that let‐7 and cyclin D1 form a feedback loop in regulating therapy response of cancer cells and cancer stem cells, and importantly, that alteration of let‐7 expression, mainly caused by cyclin D1, is a sensitive indicator for better chemotherapies response.
In Vivo Characterization of Carotid Neointimal Hyperplasia by use of Optical Coherence Tomography: Before and After Cutting Balloon Angioplasty
Authors: Blackham Kristine A. , Kim Benny S. , Jung Richard S. , Badve Chaitra , Manjila Sunil , Sila Cathy A. , Bambakidis Nicholas C.
Published: February 2015

Optical coherence tomography (OCT) is a modern intravascular imaging modality that has the capability to provide detailed, in vivo characterization of the arterial wall and atherosclerotic plaque. The current understanding of the appearance of atherosclerotic plaque via OCT is largely based on coronary arterial studies where OCT information has been employed to guide therapeutic management and permits the immediate evaluation of percutaneous intervention. The clinical success of OCT in the coronary arteries has laid the foundation for investigation of the carotid artery and thus, stroke risk assessment. We report the novel use of OCT for tissue characterization of severe stenosis subsequent to carotid artery stenting (CAS), both before and after treatment with cutting balloon angioplasty.
Safety and Efficacy of Thulium Laser Prostatectomy Versus Transurethral Resection of Prostate for Treatment of Benign Prostate Hyperplasia: A Meta‐Analysis
Authors: JIANG HongJing , ZHOU Yu
Published: February 2015

Objective

The aim of the present study was to objectively evaluate the safety and efficacy of Thulium laser prostatectmy (TmLRP) versus transurethral resection of prostate (TURP) in treating benign prostate hyperplasia (BPH).

Methods

Online databases such as Cochrane Library, PubMed, Embase, and Chinese biomedicine literature database were searched by randomized control trial (RCT), quasi‐randomized control trial (Q‐RCT) and case control study (CCSs) about TmLRP versus TURP for the treatment of BPH. After study selection, assessment and data extraction conducted, Meta‐analyses were performed by using the RevMan 5.2 software.

Results

Six studies involving 640 patients were included and the results of follow‐up time was 1 year. The results of meta‐analyses showed that: (i) safety indicators: compared with TURP, TmLRP was associated with less decrease of serum sodium salt, less blood transfusion, shorter catheterization time hospital time and more operation time. No differences were noted in the TUR syndrome, recatheterization rate, transitory urge incontinence, stress incontinence urethral stricture and retrograde ejaculation. (ii) Efficacy indicators (International Prostate Symptom Score [IPSS], post‐void residual [PVR], Qmax, quality of life [QoL]): Compared with the baseline, significant improvement in IPSS, QoL, Qmax and PVR were obvious improvement before and after surgery in both groups. There were statistical differences in IPSS at 12 months, QoL at 1, 6 months and Qmax 1, 6 months between the two groups.

Conclusions

TmLRP is a safe and effective procedure for treatment of benign prostatic hyperplasia. Compared with TURP, TmLRP was not only associated with less decrease of serum sodium salt, less blood transfusion, shorter catheterization time and hospital time, but also may be superior to TURP in efficacy.
Subsidies for Renewable Energy Facilities under Uncertainty
Authors: Adkins Roger , Paxson Dean
Published: February 2015

We derive the optimal investment timing and real option value for a facility with price and quantity uncertainty, where there might be a government subsidy proportional to production quantity. Where the subsidy is proportional to the multiplication of the price and quantity, dimensionality can be reduced. Alternatively, we provide quasi‐analytical solutions for different quantity subsidy arrangements: permanent (policy is certain); retractable; suddenly permanent; and suddenly retractable. Whether policy uncertainty acts as a disincentive for early investment depends on the type of subsidy arrangement. The greatest incentive for early investment is an actual retractable subsidy, a ‘flighty bird in hand’.