bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in nerve‐mediated contractility of the lower urinary tract in a mouse model of premature ageing
Authors: Triguero D , Lafuente‐Sanchis A , Garcia‐Pascual A
Published: December 2013

Background and Purpose

A high incidence of lower urinary tract disorders is associated with ageing. In the senescent‐accelerated prone (SAMP8) mouse strain and the senescent‐accelerated resistant (SAMR1) strain, we compared smooth muscle contractility in responses to intrinsic neurotransmitters, both in the bladder and urethra.

Experimental Approach

We analysed micturition frequency, the changes in muscle tension induced by electrical field stimulation or agonist administration, the density of nerves (adrenergic, cholinergic and nitrergic) and interstitial cells (ICs), as well as cGMP accumulation in bladder and urethral preparations.

Key Results

Senescent mice of the SAMP8 strain displayed increased micturition frequency and excitatory contractility of neurogenic origin in the bladder. While cholinergic nerve density remained unchanged, there was a mild sensitization to ACh in male mice. Potentiation in the detrusor may be also provoked by the stronger contribution of ATP, together with reduced adrenergic innervation in males and COX‐derived prostanoid production in females. The greater excitatory contractility in the urethra was probably due to the sensitization to noradrenaline, in conjunction with attenuated nitrergic relaxation. There were also fewer neuronal NOS immunoreactive (ir) nerves and vimentin‐positive ICs, although the sildenafil‐ and diethylamine‐NONOate‐induced relaxations and cGMP‐ir remained unchanged.

Conclusions and Implications

Premature senescent mice exhibit bladder and urethral hyperexcitability, coupled with reduced urethral relaxation of neurogenic origin, which could model the impaired urinary function in elderly humans. We propose that senescence‐accelerated mice provide a useful tool to analyse the basic mechanisms of age‐related changes in bladder and urethral function.
The concomitant coronary vasodilator and positive inotropic actions of the nitroxyl donor Angeli's salt in the intact rat heart: contribution of soluble guanylyl cyclase‐dependent and ‐independent mechanisms
Authors: Chin Kai Yee , Qin Chengxue , Cao Nga , Kemp‐Harper Barbara K , Woodman Owen L , Ritchie Rebecca H
Published: December 2013

Background and Purpose

The NO redox sibling nitroxyl (HNO) elicits soluble guanylyl cyclase (sGC)‐dependent vasodilatation. HNO has high reactivity with thiols, which is attributed with HNO‐enhanced left ventricular (LV) function. Here, we tested the hypothesis that the concomitant vasodilatation and inotropic actions induced by a HNO donor, Angeli's salt (sodium trioxodinitrate), were sGC‐dependent and sGC‐independent respectively.

Experimental Approach

Haemodynamic responses to Angeli's salt (10 pmol–10 μmol), alone and in the presence of scavengers of HNO (L‐cysteine, 4 mM) or of NO [hydroxocobalamin (HXC), 100 μM] or a selective inhibitor of sGC [1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ), 10 μM], a CGRP receptor antagonist (CGRP8–37, 0.1 μM) or a blocker of voltage‐dependent potassium channels [4‐aminopyridine (4‐AP), 1 mM] were determined in isolated hearts from male rats.

Key Results

Angeli's salt elicited concomitant, dose‐dependent increases in coronary flow and LV systolic and diastolic function. Both L‐cysteine and ODQ shifted (but did not abolish) the dose–response curve of each of these effects to the right, implying contributions from HNO and sGC in both the vasodilator and inotropic actions. In contrast, neither HXC, CGRP8–37 nor 4‐AP affected these actions.

Conclusions and Implications

Both vasodilator and inotropic actions of the HNO donor Angeli's salt were mediated in part by sGC‐dependent mechanisms, representing the first evidence that sGC contributes to the inotropic and lusitropic action of HNO in the intact heart. Thus, HNO acutely enhances LV contraction and relaxation, while concomitantly unloading the heart, potentially beneficial actions in failing hearts.
TRP channels in the skin
Authors: Tóth Balázs I , Oláh Attila , Szöllősi Attila Gábor , Bíró Tamás
Published: December 2013

Emerging evidence suggests that transient receptor potential (TRP) ion channels not only act as ‘polymodal cellular sensors’ on sensory neurons but are also functionally expressed by a multitude of non‐neuronal cell types. This is especially true in the skin, one of the largest organs of the body, where they appear to be critically involved in regulating various cutaneous functions both under physiological and pathophysiological conditions. In this review, we focus on introducing the roles of several cutaneous TRP channels in the regulation of the skin barrier, skin cell proliferation and differentiation, and immune functions. Moreover, we also describe the putative involvement of several TRP channels in the development of certain skin diseases and identify future TRP channel‐targeted therapeutic opportunities.

Linked Articles

This article is part of a themed section on the pharmacology of TRP channels. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐10
Reversible phospho-Smad3 signalling between tumour suppression and fibrocarcinogenesis in chronic hepatitis B infection
Authors: Deng Y-R , Yoshida K , Jin Q L , Murata M , Yamaguchi T , Tsuneyama K , Moritoki Y , Niu J Q , Matsuzaki K , Lian Z-X
Published: December 2013

Transforming growth factor (TGF)-β, type I receptor (TβRI) and c-Jun N-terminal kinases (JNK) phosphorylate Smad3 differentially to create 2 isoforms phosphorylated (p) at the COOH-terminus (C) or at the linker region (L) and regulate hepatocytic fibrocarcinogenesis. This study aimed to compare the differences between how hepatitis B virus (HBV) infection affected hepatocytic Smad3 phosphorylated isoforms before and after anti-viral therapy. To clarify the relationship between Smad3 phosphorylation and liver disease progression, we studied 10 random patients in each stage of HBV-related fibrotic liver disease (F1–4) and also 10 patients with HBV-associated HCC. To examine changes in phosphorylated Smad3 signalling before and after anti-HBV therapies, we chose 27 patients with chronic hepatitis B who underwent baseline and follow-up biopsies at 52 weeks from the start of nucleoside analogue treatments (Lamivudine 100 mg daily or Telbivudine 600 mg daily). Fibrosis stage, inflammatory activity and phosphorylated Smad3 positivity in the paired biopsy samples were compared. Hepatocytic pSmad3C signalling shifted to fibrocarcinogenic pSmad3L signalling as the livers progressed from chronic hepatitis B infection to HCC. After nucleoside analogue treatment, serum alanine aminotransferase (ALT) and HBV-DNA levels in 27 patients with HBV-related chronic liver diseases were decreased dramatically. Decrease in HBV-DNA restored pSmad3C signalling in hepatocytes, while eliminating prior fibrocarcinogenic pSmad3L signalling. Oral nucleoside analogue therapies can suppress fibrosis and reduce HCC incidence by successfully reversing phosphorylated Smad3 signalling; even liver disease progressed to cirrhosis in chronic hepatitis B patients.
In vitro cleaning potential of three different implant debridement methods
Authors: Sahrmann Philipp , Ronay Valerie , Hofer Deborah , Attin Thomas , Jung Ronald E. , Schmidlin Patrick R.
Published: December 2013

Objectives

To assess the cleaning potential of three different instrumentation methods commonly used for implant surface decontamination in vitro, using a bone defect‐simulating model.

Materials and methods

Dental implants were stained with indelible ink and mounted in resin models, which represented standardized peri‐implantitis defects with different bone defect angulations (30, 60 and 90°). Cleaning procedures were performed by either an experienced dental hygienist or a 2nd‐year postgraduate student. The treatment was repeated 20 times for each instrumentation, that is, with a Gracey curette, an ultrasonic device and an air powder abrasive device (PAD) with glycine powder. After each run, implants were removed and images were taken to detect color remnants in order to measure planimetrically the cumulative uncleaned surface area. SEM images were taken to assess micromorphologic surface changes (magnification 10,000×). Results were tested for statistical differences using two‐way ANOVA and Bonferroni correction.

Results

The areas of uncleaned surfaces (%, mean ± standard deviations) for curettes, ultrasonic tips, and airflow accounted for 24.1 ± 4.8%, 18.5 ± 3.8%, and 11.3 ± 5.4%, respectively. These results were statistically significantly different (P < 0.0001). The cleaning potential of the airflow device increased with wider defects. SEM evaluation displayed distinct surface alterations after instrumentation with steel tips, whereas glycine powder instrumentation had only a minute effect on the surface topography.

Conclusion

Within the limitations of the present in vitro model, airflow devices using glycine powders seem to constitute an efficient therapeutic option for the debridement of implants in peri‐implantitis defects. Still, some uncleaned areas remained. In wide defects, differences between instruments are more accentuated.
Factors Determining the Choice of Hunting and Trading Bushmeat in the Kilombero Valley, Tanzania
Authors: NIELSEN MARTIN REINHARDT , JACOBSEN JETTE BREDAHL , THORSEN BO JELLESMARK
Published: December 2013

Regulation of illegal bushmeat trade is a major conservation challenge in Africa. We investigated what factors are most likely to induce actors in the bushmeat trade to shift to an alternative occupation by conducting a choice experiment with 325 actors in the bushmeat trade in the Kilombero Valley, Tanzania. Specifically, we asked respondents to choose between hunting or trading bushmeat and alternative salary‐paying work, in a set of hypothetical scenarios where the attributes of these alternatives were varied and included measures of command and control, price of substitute meat, daily salary in the work option, and whether or not cows were donated to the respondent. We modeled the choice contingent on socioeconomic characteristics. The magnitude of fines and patrolling frequency had a significant but very low negative effect on the probability of choosing to engage in hunting or trading bushmeat compared with the salary of an alternative occupation. Donation of livestock and the price of substitute meats in the local market both affected the choice significantly in a negative and a positive direction, respectively. The wealthier a household was the more likely the respondent was to choose to continue hunting or trading bushmeat. On the margin, our results suggest that given current conditions in the Kilombero Valley on any given day 90% of the respondents would choose salary work at US$3.37/day over their activities in the bushmeat trade, all else equal.

Factores que Determinan la Elección de Cazar y Vender Carne de Caza en el Valle Kilombero, Tanzania
Identification of Areas in Brazil that Optimize Conservation of Forest Carbon, Jaguars, and Biodiversity
Authors: DE BARROS ALAN E. , MACDONALD EWAN A. , MATSUMOTO MARCELO H. , PAULA ROGÉRIO C. , NIJHAWAN SAHIL , MALHI Y. , MACDONALD DAVID W.
Published: December 2013

A major question in global environmental policy is whether schemes to reduce carbon pollution through forest management, such as Reducing Emissions from Deforestation and Degradation (REDD+), can also benefit biodiversity conservation in tropical countries. We identified municipalities in Brazil that are priorities for reducing rates of deforestation and thus preserving carbon stocks that are also conservation targets for the endangered jaguar (Panthera onca) and biodiversity in general. Preliminary statistical analysis showed that municipalities with high biodiversity were positively associated with high forest carbon stocks. We used a multicriteria decision analysis to identify municipalities that offered the best opportunities for the conservation of forest carbon stocks and biodiversity conservation under a range of scenarios with different rates of deforestation and carbon values. We further categorized these areas by their representativeness of the entire country (through measures such as percent forest cover) and an indirect measure of cost (number of municipalities). The municipalities that offered optimal co‐benefits for forest carbon stocks and conservation were termed REDDspots (n = 159), and their spatial distribution was compared with the distribution of current and proposed REDD projects (n = 135). We defined REDDspots as the municipalities that offer the best opportunities for co‐benefits between the conservation of forest carbon stocks, jaguars, and other wildlife. These areas coincided in 25% (n = 40) of municipalities. We identified a further 95 municipalities that may have the greatest potential to develop additional REDD+ projects while also targeting biodiversity conservation. We concluded that REDD+ strategies could be an efficient tool for biodiversity conservation in key locations, especially in Amazonian and Atlantic Forest biomes.

Identificación de Áreas en Brasil que Optimizan la Conservación del Carbono del Bosque, Jaguares y la Biodiversidad.
Wildlife Connectivity Approaches and Best Practices in U.S. State Wildlife Action Plans
Authors: LACHER IARA , WILKERSON MARIT L.
Published: December 2013

As habitat loss and fragmentation threaten biodiversity on large geographic scales, creating and maintaining connectivity of wildlife populations is an increasingly common conservation objective. To assess the progress and success of large‐scale connectivity planning, conservation researchers need a set of plans that cover large geographic areas and can be analyzed as a single data set. The state wildlife action plans (SWAPs) fulfill these requirements. We examined 50 SWAPs to determine the extent to which wildlife connectivity planning, via linkages, is emphasized nationally. We defined linkage as connective land that enables wildlife movement. For our content analysis, we identified and quantified 6 keywords and 7 content criteria that ranged in specificity and were related to linkages for wide‐ranging terrestrial vertebrates and examined relations between content criteria and statewide data on focal wide‐ranging species, spending, revenue, and conserved land. Our results reflect nationwide disparities in linkage conservation priorities and highlight the continued need for wildlife linkage planning. Only 30% or less of the 50 SWAPs fulfilled highly specific content criteria (e.g., identifying geographic areas for linkage placement or management). We found positive correlations between our content criteria and statewide data on percent conserved land, total focal species, and spending on parks and recreation. We supplemented our content analysis with interviews with 17 conservation professionals to gain specific information about state‐specific context and future directions of linkage conservation. Based on our results, relevant literature, and interview responses, we suggest the following best practices for wildlife linkage conservation plans: collect ecologically meaningful background data; be specific; establish community‐wide partnerships; and incorporate sociopolitical and socioeconomic information.

Acercamientos a la Conectividad de Vida Silvestre y las Mejores Prácticas en los Planes de Acción de Vida Silvestre Estatales en los Estados Unidos
Using Changes in Agricultural Utility to Quantify Future Climate‐Induced Risk to Conservation
Authors: ESTES LYNDON D. , PAROZ LYDIE‐LINE , BRADLEY BETHANY A. , GREEN JONATHAN M.H. , HOLE DAVID G. , HOLNESS STEPHEN , ZIV GUY , OPPENHEIMER MICHAEL G. , WILCOVE DAVID S.
Published: December 2013

Much of the biodiversity‐related climate change impacts research has focused on the direct effects to species and ecosystems. Far less attention has been paid to the potential ecological consequences of human efforts to address the effects of climate change, which may equal or exceed the direct effects of climate change on biodiversity. One of the most significant human responses is likely to be mediated through changes in the agricultural utility of land. As farmers adapt their practices to changing climates, they may increase pressure on some areas that are important to conserve (conservation lands) whereas lessening it on others. We quantified how the agricultural utility of South African conservation lands may be altered by climate change. We assumed that the probability of an area being farmed is linked to the economic benefits of doing so, using land productivity values to represent production benefit and topographic ruggedness as a proxy for costs associated with mechanical workability. We computed current and future values of maize and wheat production in key conservation lands using the DSSAT4.5 model and 36 crop‐climate response scenarios. Most conservation lands had, and were predicted to continue to have, low agricultural utility because of their location in rugged terrain. However, several areas were predicted to maintain or gain high agricultural utility and may therefore be at risk of near‐term or future conversion to cropland. Conversely, some areas were predicted to decrease in agricultural utility and may therefore prove easier to protect from conversion. Our study provides an approximate but readily transferable method for incorporating potential human responses to climate change into conservation planning.

Uso de Cambios en la Utilidad Agrícola para Cuantificar Riesgos Futuros para la Conservación Inducidos por el Clima
Quantifying Preferences for the Natural World Using Monetary and Nonmonetary Assessments of Value
Authors: DALLIMER MARTIN , TINCH DUGALD , HANLEY NICK , IRVINE KATHERINE N. , ROUQUETTE JAMES R. , WARREN PHILIP H. , MALTBY LORRAINE , GASTON KEVIN J. , ARMSWORTH PAUL R.
Published: December 2013

Given that funds for biodiversity conservation are limited, there is a need to understand people's preferences for its different components. To date, such preferences have largely been measured in monetary terms. However, how people value biodiversity may differ from economic theory, and there is little consensus over whether monetary metrics are always appropriate or the degree to which other methods offer alternative and complementary perspectives on value. We used a choice experiment to compare monetary amounts recreational visitors to urban green spaces were willing to pay for biodiversity enhancement (increases in species richness for birds, plants, and aquatic macroinvertebrates) with self‐reported psychological gains in well‐being derived from visiting the same sites. Willingness‐to‐pay (WTP) estimates were significant and positive, and respondents reported high gains in well‐being across 3 axes derived from environmental psychology theories (reflection, attachment, continuity with past). The 2 metrics were broadly congruent. Participants with above‐median self‐reported well‐being scores were willing to pay significantly higher amounts for enhancing species richness than those with below‐median scores, regardless of taxon. The socio‐economic and demographic background of participants played little role in determining either their well‐being or the probability of choosing a paying option within the choice experiment. Site‐level environmental characteristics were only somewhat related to WTP, but showed strong associations with self‐reported well‐being. Both approaches are likely to reflect a combination of the environmental properties of a site and unobserved individual preference heterogeneity for the natural world. Our results suggest that either metric will deliver mutually consistent results in an assessment of environmental preferences, although which approach is preferable depends on why one wishes to measure values for the natural world.

Preferencias de Cuantificación para el Mundo Natural Usando Estudios de Valor Monetario y No Monetario.
Factors Mediating Co‐Occurrence of an Economically Valuable Introduced Fish and Its Native Frog Prey
Authors: HARTMAN ROSEMARY , POPE KAREN , LAWLER SHARON
Published: December 2013

Habitat characteristics mediate predator–prey coexistence in many ecological systems but are seldom considered in species introductions. When economically important introduced predators are stocked despite known negative impacts on native species, understanding the role of refuges, landscape configurations, and community interactions can inform habitat management plans. We measured these factors in basins with introduced trout (Salmonidae) and the Cascades frog (Rana cascadae) to determine, which are responsible for observed patterns of co‐occurrence of this economically important predator and its native prey. Large, vegetated shallows were strongly correlated to co‐occurrence, and R. cascadae larvae occur in shallower water when fish are present, presumably to escape predation. The number of nearby breeding sites of R. cascadae was also correlated to co‐occurrence, but only when the western toad (Anaxyrus boreas) was present. Because A. boreas larvae are unpalatable to fish and resemble R. cascadae, they may provide protection from trout via Batesian mimicry. Although rescue‐effect dispersal from nearby populations may maintain co‐occurrence, within‐lake factors proved more important for predicting co‐occurrence. Learning which factors allow co‐occurrence between economically important introduced species and their native prey enables managers to make better‐informed stocking decisions.

Factores que Median la Co‐Ocurrencia de un Pez Introducido con Valor Económico y su Presa, una Rana Nativa
Potential Impacts of Global Warming on the Diversity and Distribution of Stream Insects in South Korea
Authors: LI FENGQING , KWON YONG‐SU , BAE MI‐JUNG , CHUNG NAMIL , KWON TAE‐SUNG , PARK YOUNG‐SEUK
Published: December 2013

Globally, the East Asian monsoon region is one of the richest environments in terms of biodiversity. The region is undergoing rapid human development, yet its river ecosystems have not been well studied. Global warming represents a major challenge to the survival of species in this region and makes it necessary to assess and reduce the potential consequences of warming on species of conservation concern. We projected the effects of global warming on stream insect (Ephemeroptera, Odonata, Plecoptera, and Trichoptera [EOPT]) diversity and predicted the changes of geographical ranges for 121 species throughout South Korea. Plecoptera was the most sensitive (decrease of 71.4% in number of species from the 2000s through the 2080s) order, whereas Odonata benefited (increase of 66.7% in number of species from the 2000s through the 2080s) from the effects of global warming. The impact of global warming on stream insects was predicted to be minimal prior to the 2060s; however, by the 2080s, species extirpation of up to 20% in the highland areas and 2% in the lowland areas were predicted. The projected responses of stream insects under global warming indicated that species occupying specific habitats could undergo major reductions in habitat. Nevertheless, habitat of 33% of EOPT (including two‐thirds of Odonata and one‐third of Ephemeroptera, Plecoptera, and Trichoptera) was predicted to increase due to global warming. The community compositions predicted by generalized additive models varied over this century, and a large difference in community structure in the highland areas was predicted between the 2000s and the 2080s. However, stream insect communities, especially Odonata, Plecoptera, and Trichoptera, were predicted to become more homogenous under global warming.

Impacto Potencial del Calentamiento Global sobre la Diversidad y la Distribución de Insectos de Arroyo en Corea del Sur
Experiencing Biodiversity as a Bridge over the Science–Society Communication Gap
Authors: MEINARD YVES , QUÉTIER FABIEN
Published: December 2013

Drawing on the idea that biodiversity is simply the diversity of living things, and that everyone knows what diversity and living things mean, most conservation professionals eschew the need to explain the many complex ways in which biodiversity is understood in science. On many biodiversity‐related issues, this lack of clarity leads to a communication gap between science and the general public, including decision makers who must design and implement biodiversity policies. Closing this communication gap is pivotal to the ability of science to inform sound environmental decision making. To address this communication gap, we propose a surrogate of biodiversity for communication purposes that captures the scientific definition of biodiversity yet can be understood by nonscientists; that is, biodiversity as a learning experience. The prerequisites of this or any other biodiversity communication surrogate are that it should have transdisciplinary relevance; not be measurable; be accessible to a wide audience; be usable to translate biodiversity issues; and understandably encompass biodiversity concepts. Biodiversity as a learning experience satisfies these prerequisites and is philosophically robust. More importantly, it can effectively contribute to closing the communication gap between biodiversity science and society at large.

Experimentando la Biodiversidad como un Puente sobre el Vacío entre la Comunicación Ciencia‐Sociedad
Health‐related quality of life after surgery for advanced and recurrent rectal cancer: a nationwide prospective study
Authors: Thaysen H. V. , Jess P. , Rasmussen P. C. , Nielsen M. B. , Laurberg S.
Published: December 2013

Aim

Advances in the treatment of rectal cancer have made it possible to perform complex rectal cancer surgery (COMP‐RCS) in patients with primary advanced rectal cancer penetrating beyond the total mesorectal excision planes and in patients with locally recurrent rectal cancer. The aim of this study was to examine health‐related quality of life (HRQoL) before and during the first 2 years after COMP‐RCS.

Method

Between 2001 and 2008, 180 patients were treated with COMP‐RCS at Aarhus University Hospital. HRQoL was assessed preoperatively and 3, 6, 12, 18 and 24 months after surgery using three questionnaires. The results were compared with those for patients treated with standard rectal cancer surgery (STAN‐RCS) and with data from the general Danish population (NORM‐data).

Results

One hundred and twenty‐two (68%) patients responded to the questionnaires. Of these 80 (66%) with disease‐free survival for 2 years after surgery were included in the main analysis. The lowest level of functioning and the highest degree of symptoms were reported preoperatively. The majority of the HRQoL scales improved or remained stable during the first postoperative year; a decrease was observed for body image only. One year after surgery, HRQoL in patients treated with COMP‐RSC was comparable to that for patients treated with STAN‐RCS. Lower levels were found for physical and emotional role functioning, compared with NORM‐data.

Conclusion

Patients treated with COMP‐RCS experienced improvement in HRQoL in the first year after surgery. One year after surgery, HRQoL was similar to that of patients treated with STAN‐RCS. Compared with NORM‐data, lower levels were found for physical and emotional role functioning.
Land Sparing Versus Land Sharing: Moving Forward
Authors: Fischer Joern , Abson David J. , Butsic Van , Chappell M. Jahi , Ekroos Johan , Hanspach Jan , Kuemmerle Tobias , Smith Henrik G. , von Wehrden Henrik
Published: December 2013

To address the challenges of biodiversity conservation and commodity production, a framework has been proposed that distinguishes between the integration (“land sharing”) and separation (“land sparing”) of conservation and production. Controversy has arisen around this framework partly because many scholars have focused specifically on food production rather than more encompassing notions such as land scarcity or food security. Controversy further surrounds the practical value of partial trade‐off analyses, the ways in which biodiversity should be quantified, and a series of scale effects that are not readily accounted for. We see key priorities for the future in (1) addressing these issues when using the existing framework, and (2) developing alternative, holistic ways to conceptualise challenges related to food, biodiversity, and land scarcity.
The prognosis and treatment outcomes of patients with recurrent hepatocellular carcinoma after liver transplantation
Authors: Roh Young‐Nam , David Kwon Choon Hyuck , Song Sanghyun , Shin Milljae , Man Kim Jong , Kim Sungjoo , Joh Jae‐Won , Lee Suk‐Koo
Published: December 2013

Liver transplantation (LT) is performed in patients with hepatocellular carcinoma (HCC), but recurrent HCC after LT remains a problem. We retrospectively reviewed the data from 63 patients with recurrent HCC who underwent LT at a single institution between September 1996 and March 2011 to determine the prognosis of patients with recurrent HCC after LT. A survival analysis was performed with the preoperative data, histological findings, patterns of recurrence, and treatment methods. Univariate and multivariate analyses were performed to determine the factors associated with early (<1 yr) cancer‐related death. The independent prognostic factors, according to the multivariate analysis, were recurrence within six months (hazards ratio [HR] = 4.557, p = 0.021) and initial multiple‐organ involvement (HR = 5.494, p = 0.015). The survival rates of patients differed according to the treatment type. The combined treatment with local and systemic treatment resulted in increased survival even in patients with HCC recurrences involving multiple organs.
Flow cytometry assessment of graft‐infiltrating lymphocytes can accurately identify acute rejection in kidney transplants
Authors: Xavier Paula D.P. , Lema Gloria L. , Magalhães Maria C. , Teixeira‐Pinto Armando , Sampaio‐Norton Susana , Gaião Sérgio , Guimarães Tiago , Oliveira José G.G.
Published: December 2013

Background

Previously, we have reported that flow cytometry analysis of fine‐needle aspirates can accurately predict rejection in kidney transplants treated with cyclosporine–azathioprine–prednisolone. In this study, we examined this technique's accuracy using current immunosuppression.

Methods

Kidney transplant recipients were treated with calcineurin inhibitors, mycophenolate mofetil, and prednisolone: 92 remained rejection‐free – Group I – and 37 developed acute rejection – Group II. An allograft aspiration specimen and peripheral blood were collected from Group I on post‐transplant day 7 and from Group II on the day of clinical rejection.

Results

Significant changes were seen in both aspiration and peripheral blood samples in several T cell subsets when comparing Groups I and II. A sensitivity of 94.6%, specificity of 85%, and AUC = 0.966 were observed through combining CD8DR with CD3CD69 values from aspiration specimen; the corresponding AUC in peripheral blood was 0.847. Irreversible rejections displayed a significantly higher activation score (p = 0.024).

Conclusions

Flow cytometry analysis of aspiration specimen achieved high diagnostic performance in renal transplants through studying CD8DR and CD3CD69 under current immunosuppressive therapy. Peripheral blood analysis, although not significant, showed the same trend. The activation score anticipated the irreversibility of rejection. The data suggest this test, through an easily tolerated technique, merits further diagnostic use.
Endothelial nitric oxide synthase polymorphism influences renal allograft outcome
Authors: Uyar Murathan , Sezer Siren , Ozdemir Fatma Nurhan , Kulah Eyup , Arat Zubeyde , Atac Fatma Belgin , Haberal Mehmet
Published: December 2013

Background

Atherosclerotic lesions within the graft are considered to be a major cause of interstitial fibrosis/tubular atrophy (IF/TA). We evaluated the factors that influence the development of IF/TA and three‐ and five‐yr graft survival including nitric oxide synthase (eNOS) and angiotensin II type 1 and type 2 receptor gene polymorphism.

Methods

Seventy‐one male and 35 female patients (age: 34.9 ± 11.2 yr) who underwent living‐related renal transplantation were included. Angiotensin type 1 and type 2 receptor gene polymorphisms and eNOS intron 4 gene polymorphism were analyzed. The pre‐ and post‐transplant laboratory data, patient characteristics, acute rejection episodes, and presence of IF/TA were evaluated.

Results

Patients with the bb allele of eNOS gene had a lower prevalence of post‐transplant third year (12.6% and 38.5%, p = 0.005) and fifth year IF/TA (46.6% and 82.3%, p = 0.02) and a lower incidence of five‐yr graft failure (35.4% and 55.6%, p < 0.005). The eNOS gene polymorphism was independent and was the most prominent factor associated with third and fifth year IF/TA (p = 0.01, RR: 29.72, and p = 0.03, RR: 4.1, respectively). No significant relationship existed when angiotensin II gene polymorphisms were considered.

Conclusions

We concluded that recipient eNOS gene polymorphism can predict IF/TA, and the presence of the bb allele is associated with better graft outcome.
Preoperative left ventricular hypertrophy is associated with reduced patient survival after liver transplantation
Authors: Darstein F. , König C. , Hoppe‐Lotichius M. , Grimm D. , Knapstein J. , Mittler J. , Zimmermann A. , Otto G. , Lang H. , Galle P.R. , Zimmermann T.
Published: December 2013

Left ventricular hypertrophy (LVH) has been described in the context of cirrhotic cardiomyopathy. The influence of LVH on survival of liver transplant (LT) recipients has not been clarified. Therefore, we evaluated the effect of LVH on survival in LT recipients. In total, data from 352 LT patients were analyzed. LVH was diagnosed by echocardiographic measurement of left ventricular wall thickness before LT. Patients were followed up for a mean of 4.2 yr. LVH was diagnosed in 135 (38.4%) patients. Patients with LVH had significantly more frequently male gender (p = 0.046), diastolic dysfunction (p < 0.001), and hepatocellular carcinoma (HCC; p = 0.004). Furthermore, LVH patients were older (p < 0.001) and had a higher body mass index (BMI; p = 0.001). There was no difference in frequency of arterial hypertension, pre‐transplant diabetes mellitus, or etiology of liver cirrhosis. Patients without LVH had a better survival (log rank: p = 0.05) compared with LVH patients. In a multivariate Cox regression LVH (p = 0.031), end‐stage renal disease (ESRD; p = 0.003) and lack of arterial hypertension (p = 0.004) but not MELD score (p = 0.885) were associated with poorer survival.

Conclusion

LVH is frequently diagnosed in patients on the waiting list and influences survival after LT.
Patients' expectations and experiences of rehabilitation following lung transplantation
Authors: Fuller L.M. , Button B. , Tarrant B. , Battistuzzo C.R. , Braithwaite M. , Snell G. , Holland A.E.
Published: December 2013

Introduction

Exercise rehabilitation is a key element of care following lung transplantation; however, little is known about the patients' experience of rehabilitation, or whether it meets the needs of this complex patient group. This qualitative study explored patients' expectations of a supervised exercise rehabilitation program following lung transplantation.

Methods

Participants undertook two semi‐structured interviews, one before and one after the rehabilitation program. Interviews were digitally recorded, and themes were developed using line‐by‐line iterative thematic analysis and grounded theory.

Results

Eighteen adults (11 females) with mean age of 52 participated in a mean of 26 sessions of exercise training. Themes were (i) desire for normalcy including resuming family roles and performing everyday activities; (ii) the importance of rehabilitation as the mechanism for how this transformation occurred; (iii) the benefits of exercising in a group setting; and (iv) the limitations on rehabilitation that were imposed by comorbidities, either existing pre‐transplant or occurring as a postoperative sequelae.

Conclusion

Post‐transplant exercise rehabilitation was perceived as a highly valuable tool that assisted recipients to return to “normal life.” Group exercise was motivational, offered peer support, and therefore was advantageous to assist patients to achieve their desired physical performance level following transplantation.
Feasibility for a large scale mouse mutagenesis by injecting CRISPR/Cas plasmid into zygotes
Authors: Mashiko Daisuke , Young Samantha A. M. , Muto Masanaga , Kato Hirotaka , Nozawa Kaori , Ogawa Masaki , Noda Taichi , Kim Yeon‐Joo , Satouh Yuhkoh , Fujihara Yoshitaka , Ikawa Masahito
Published: December 2013

The recombinant clustered regulatory interspaced short palindromic repeats (CRISPR)/Cas system has opened a new era for mammalian genome editing. Here, we constructed pX330 plasmids expressing humanized Cas9 (hCas9) and single guide RNAs (sgRNAs) against mouse genes and validated them both in vitro and in vivo. When we randomly chose 291 target sequences within protein coding regions of 73 genes, an average number of off‐target candidates (exact match 13 nucleotides from 3′ target and NGG) found by Bowtie software was 9.2 ± 21.0 (~1.8 times more than the estimated value, 5.2). We next validated their activity by observing green fluorescence reconstituted by homology dependent repair (HDR) of an EGFP expression cassette in HEK293T cells. Of the pX330 plasmids tested, 81.8% (238/291) were found to be functional in vitro. We finally injected the validated pX330 plasmids into mouse zygotes in its circular form against 32 genes (including two genes previously tested) and obtained mutant mice at a 52.9 ± 22.3% (100/196) mutation frequency. Among the pups carrying mutations on the autosomes, 43.6% (47/96) carried the mutations in both alleles. When off‐target candidate sites were examined in 63 mutant mice, 0.8% (3/382) were mutated. We conclude that our method provides a simple, efficient, and cost‐effective way for mammalian gene editing that is applicable for large scale mutagenesis in mammals.
Spatially extended forward suppression in primate auditory cortex
Authors: Zhou Yi , Wang Xiaoqin
Published: December 2013

When auditory neurons are stimulated with a pair of sounds, the preceding sound can inhibit the neural responses to the succeeding sound. This phenomenon, referred to as ‘forward suppression’, has been linked to perceptual forward masking. Previous studies investigating forward suppression typically measured the interaction between masker and probe sounds using a fixed sound location. However, in natural environments, interacting sounds often come from different spatial locations. The present study investigated two questions regarding forward suppression in the primary auditory cortex and adjacent caudal field of awake marmoset monkeys. First, what is the relationship between the location of a masker and its effectiveness in inhibiting neural response to a probe? Second, does varying the location of a masker change the spectral profile of forward suppression? We found that a masker can inhibit a neuron's response to a probe located at a preferred location even when the masker is located at a non‐preferred location of a neuron. This is especially so for neurons in the caudal field. Furthermore, we found that the strongest forward suppression is observed when a masker's frequency is close to the best frequency of a neuron, regardless of the location of the masker. These results reveal, for the first time, the stability of forward masking in cortical processing of multiple sounds presented from different locations. They suggest that forward suppression in the auditory cortex is spectrally specific and spatially broad with respect to the frequency and location of the masker, respectively.
Intact brown adipose tissue thermogenesis is required for restorative sleep responses after sleep loss
Authors: Szentirmai Éva , Kapás Levente
Published: December 2013

Metabolic signals related to feeding and body temperature regulation have profound effects on vigilance. Brown adipose tissue (BAT) is a key effector organ in the regulation of metabolism in several species, including rats and mice. Significant amounts of active BAT are also present throughout adulthood in humans. The metabolic activity of BAT is due to the tissue‐specific presence of the uncoupling protein‐1 (UCP‐1). To test the involvement of BAT thermogenesis in sleep regulation, we investigated the effects of two sleep‐promoting stimuli in UCP‐1‐deficient mice. Sleep deprivation by gentle handling increased UCP‐1 mRNA expression in BAT and elicited rebound increases in non‐rapid‐eye‐movement sleep and rapid‐eye‐movement sleep accompanied by elevated slow‐wave activity of the electroencephalogram. The rebound sleep increases were significantly attenuated, by ~ 35–45%, in UCP‐1‐knockout (KO) mice. Wild‐type (WT) mice with capsaicin‐induced sensory denervation of the interscapular BAT pads showed similar impairments in restorative sleep responses after sleep deprivation, suggesting a role of neuronal sleep‐promoting signaling from the BAT. Exposure of WT mice to 35 °C ambient temperature for 5 days led to increased sleep and body temperature and suppressed feeding and energy expenditure. Sleep increases in the warm environment were significantly suppressed, by ~ 50%, in UCP‐1‐KO animals while their food intake and energy expenditure did not differ from those of the WTs. These results suggest that the metabolic activity of the BAT plays a role in generating a metabolic environment that is permissive for optimal sleep. Impaired BAT function may be a common underlying cause of sleep insufficiency and metabolic disorders.
Herbivory makes major contributions to ecosystem carbon and nutrient cycling in tropical forests
Authors: Metcalfe Daniel B. , Asner Gregory P. , Martin Roberta E. , Silva Espejo Javier E. , Huasco Walter Huaraca , Farfán Amézquita Felix F. , Carranza‐Jimenez Loreli , Galiano Cabrera Darcy F. , Baca Liliana Durand , Sinca Felipe , Huaraca Quispe Lidia P. , Taype Ivonne Alzamora , Mora Luzmila Eguiluz , Dávila Angela Rozas , Solórzano Marlene Mamani , Puma Vilca Beisit L. , Laupa Román Judith M. , Guerra Bustios Patricia C. , Revilla Norma Salinas , Tupayachi Raul , Girardin Cécile A. J. , Doughty Christopher E. , Malhi Yadvinder
Published: December 2013

The functional role of herbivores in tropical rainforests remains poorly understood. We quantified the magnitude of, and underlying controls on, carbon, nitrogen and phosphorus cycled by invertebrate herbivory along a 2800 m elevational gradient in the tropical Andes spanning 12°C mean annual temperature. We find, firstly, that leaf area loss is greater at warmer sites with lower foliar phosphorus, and secondly, that the estimated herbivore‐mediated flux of foliar nitrogen and phosphorus from plants to soil via leaf area loss is similar to, or greater than, other major sources of these nutrients in tropical forests. Finally, we estimate that herbivores consume a significant portion of plant carbon, potentially causing major shifts in the pattern of plant and soil carbon cycling. We conclude that future shifts in herbivore abundance and activity as a result of environmental change could have major impacts on soil fertility and ecosystem carbon sequestration in tropical forests.
The microtubule associated protein tau H1 haplotype and risk of essential tremor
Authors: Clark L. N. , Liu X. , Parmalee N. L. , Hernandez N. , Louis E. D.
Published: December 2013

Background and purpose

Two recent studies investigated the association of the microtubule associated protein tau (MAPT) H1 haplotype, a known risk factor for neurodegenerative disease including progressive supranuclear palsy and Parkinson's disease (PD), with essential tremor (ET).

Methods

To confirm this association in a different population the distribution of allele and genotype frequencies for the MAPT H1/H2 tagging single‐nucleotide polymorphism (SNP) rs1052553 in ET cases and controls enrolled in a clinical‐epidemiological study of ET at Columbia University was analyzed.

Results

Overall, no association was observed between ET and the MAPT H1 haplotype. The analysis was also restricted to clinical subtypes including early‐onset (≤40 years of age), Ashkenazi Jewish ancestry, white non‐Ashkenazi, or ET cases with a ‘definite’ or ‘probable/possible’ diagnosis; none of these stratified analyses showed evidence of association with ET. A meta‐analysis of the H1/H2 tagging SNP rs1052553 in published data sets and the H1 haplotype with risk for ET in the current study was also performed and did not find evidence for association.

Conclusions

The inconsistent reports of association of MAPT H1 in three emerging studies (our own and two published studies) may reflect sampling issues and/or clinical heterogeneity in these populations.
Cerebrospinal fluid biomarkers of β‐amyloid metabolism and neuronal damage in epileptic seizures
Authors: Shahim P. , Rejdak R. , Ksiazek P. , Blennow K. , Zetterberg H. , Mattsson N. , Rejdak K.
Published: December 2013

Background and purpose

The main objectives of this study were to investigate if epileptic seizures have effects on brain metabolism of β‐amyloid (Aβ), as reflected by cerebrospinal fluid (CSF) levels of different isoforms of Aβ peptides and soluble amyloid precursor protein (APP), and neuronal degeneration, as reflected by CSF biomarker signs of acute neuronal injury.

Methods

Forty‐five patients were included, 21 of whom had single generalized tonic‐clonic seizures sGTCS), 11 had repetitive GTCS, 7 had repetitive partial seizures (rPS), 6 had single partial seizure (sPS) and 4 fulfilled the criterion for non‐convulsive status epilepticus (nSE). CSF was analyzed for Aβx‐38, Aβx‐40, Aβx‐42, Aβ1‐42, soluble APP fragments (sAPP‐α/β), total‐tau (T‐tau) and phosphorylated tau (P‐tau), as well as heart‐type fatty acid binding protein (H‐FABP).

Results

Patients with seizures had decreased levels of T‐tau (P = 0.0016) and P‐tau (P = 0.0028) compared with controls, but no differences in H‐FABP (P = 0.67). There were no overall differences in Aβ or sAPP peptides between seizure patients and controls. In patients with rPS, the levels of Aβx‐38 and Aβx‐40 were elevated compared with nSE (P < 0.01), sPS (P < 0.05) and controls (P < 0.05), and Aβx‐42 was elevated in rPS relative to nSE (P < 0.05).

Conclusions

The findings of this study argue against acute neuronal injury following medically treated seizures but suggest that seizures may reduce CSF levels of tau. Although seizures generally did not affect CSF levels of Aβ or sAPP peptides, our findings suggest that different types of seizures may have different effects on APP metabolism.