bluuebunny/crossref_metadata_2025 huggingface dataset:
The arbuscular mycorrhizal symbiosis promotes the systemic induction of regulatory defence‐related genes in rice leaves and confers resistance to pathogen infection
Authors: CAMPOS‐SORIANO LIDIA , GARCÍA‐MARTÍNEZ JOSÉ , SEGUNDO BLANCA SAN
Published: December 2011

Arbuscular mycorrhizal (AM) symbioses are mutualistic associations between soil fungi and most vascular plants. Their association benefits the host plant by improving nutrition, mainly phosphorus nutrition, and by providing increased capability to cope with adverse conditions. In this study, we investigated the transcriptional changes triggered in rice leaves as a result of AM symbiosis, focusing on the relevance of the plant defence response. We showed that root colonization by the AM fungusGlomus intraradicesis accompanied by the systemic induction of genes that play a regulatory role in the host defence response, such asOsNPR1,OsAP2,OsEREBPandOsJAmyb. Genes involved in signal transduction processes (OsDUF26andOsMPK6) and genes that function in calcium‐mediated signalling processes (OsCBP,OsCaMandOsCML4) are also up‐regulated in leaves of mycorrhizal rice plants in the absence of pathogen infection. In addition, the mycorrhizal rice plants exhibit a stronger induction of defence marker genes [i.e. pathogenesis‐related (PR) genes] in their leaves in response to infection by the blast fungusMagnaporthe oryzae. Evidence indicates that mycorrhizal rice plants show enhanced resistance to the rice blast fungus. Overall, these results suggest that the protective effect of the AM symbiosis in rice plants relies on both the systemic activation of defence regulatory genes in the absence of pathogen challenge and the priming for stronger expression of defence effector genes during pathogen infection. The possible mechanisms involved in the mycorrhiza‐induced resistance toM. oryzaeinfection are discussed.
No‐analog climates and shifting realized niches during the late quaternary: implications for 21st‐century predictions by species distribution models
Authors: Veloz Samuel D. , Williams John W. , Blois Jessica L. , He Feng , Otto‐Bliesner Bette , Liu Zhengyu
Published: December 2011

Empirically derived species distributions models (SDMs) are increasingly relied upon to forecast species vulnerabilities to future climate change. However, many of the assumptions of SDMs may be violated when they are used to project species distributions across significant climate change events. In particular, SDM's in theory assume stable fundamental niches, but in practice, they assume stable realized niches. The assumption of a fixed realized niche relative to climate variables remains unlikely for various reasons, particularly if novel future climates open up currently unavailable portions of species’ fundamental niches. To demonstrate this effect, we compare the climate distributions for fossil‐pollen data from 21 to 15 ka bp (relying on paleoclimate simulations) when communities and climates with no modern analog were common across North America to observed modern pollen assemblages. We test how well SDMs are able to project 20th century pollen‐based taxon distributions with models calibrated using data from 21 to 15 ka. We find that taxa which were abundant in areas with no‐analog late glacial climates, such as Fraxinus, Ostrya/Carpinus and Ulmus, substantially shifted their realized niches from the late glacial period to present. SDMs for these taxa had low predictive accuracy when projected to modern climates despite demonstrating high predictive accuracy for late glacial pollen distributions. For other taxa, e.g. Quercus, Picea, Pinus strobus, had relatively stable realized niches and models for these taxa tended to have higher predictive accuracy when projected to present. Our findings reinforce the point that a realized niche at any one time often represents only a subset of the climate conditions in which a taxon can persist. Projections from SDMs into future climate conditions that are based solely on contemporary realized distributions are potentially misleading for assessing the vulnerability of species to future climate change.
A global assessment of invasive plant impacts on resident species, communities and ecosystems: the interaction of impact measures, invading species' traits and environment
Authors: Pyšek Petr , Jarošík Vojtěch , Hulme Philip E. , Pergl Jan , Hejda Martin , Schaffner Urs , Vilà Montserrat
Published: December 2011

With the growing body of literature assessing the impact of invasive alien plants on resident species and ecosystems, a comprehensive assessment of the relationship between invasive species traits and environmental settings of invasion on the characteristics of impacts is needed. Based on 287 publications with 1551 individual cases that addressed the impact of 167 invasive plant species belonging to 49 families, we present the first global overview of frequencies of significant and non‐significant ecological impacts and their directions on 15 outcomes related to the responses of resident populations, species, communities and ecosystems. Species and community outcomes tend to decline following invasions, especially those for plants, but the abundance and richness of the soil biota, as well as concentrations of soil nutrients and water, more often increase than decrease following invasion. Data mining tools revealed that invasive plants exert consistent significant impacts on some outcomes (survival of resident biota, activity of resident animals, resident community productivity, mineral and nutrient content in plant tissues, and fire frequency and intensity), whereas for outcomes at the community level, such as species richness, diversity and soil resources, the significance of impacts is determined by interactions between species traits and the biome invaded. The latter outcomes are most likely to be impacted by annual grasses, and by wind pollinated trees invading mediterranean or tropical biomes. One of the clearest signals in this analysis is that invasive plants are far more likely to cause significant impacts on resident plant and animal richness on islands rather than mainland. This study shows that there is no universal measure of impact and the pattern observed depends on the ecological measure examined. Although impact is strongly context dependent, some species traits, especially life form, stature and pollination syndrome, may provide a means to predict impact, regardless of the particular habitat and geographical region invaded.
Evaluation of long‐distance dispersal of Culicoides midges into northern Australia using a migration model
Authors: EAGLES D. , DEVESON T. , WALKER P. J. , ZALUCKI M. P. , DURR P.
Published: December 2011

The introduction of novel bluetongue serotypes and genotypes into northern Australia is considered possible via the long‐distance windborne dispersal of Culicoides (Diptera: Ceratopogonidae) vectors from Southeast Asia. Initial findings from simulation modelling of potential dispersal over a 15‐year period revealed that the greatest risk for incursion of windborne Culicoides from the island of Timor into northern Australia occurs during December–March. The regions at greatest risk for incursion include the top end of the Northern Territory and the Kimberley region in Western Australia, but there is potential for more widespread dispersal into northern Australia based on Timor as the putative source. The establishment of a more pathogenic strain of the virus, or of a novel Culicoides vector introduced by such inter‐continental dispersal events, could dramatically alter Australia's current bluetongue disease status.
Effect of pregnancy on immunological and virological outcomes of women on ART: a prospective cohort study in rural Uganda, 2004–2009
Authors: Mayanja Billy N. , Shafer Leigh Anne , Van der Paal Lieve , Kyakuwa Nassim , Ndembi Nicaise , Hughes Peter , Maher Dermot , Grosskurth Heiner
Published: December 2011

Objectives  Before antiretroviral therapy (ART) introduction, pregnancy was associated with a sustained drop in CD4 cell count in HIV‐infected women. We examined the effects of pregnancy on immunological and virological ART outcomes.

Methods  Between January 2004 and March 2009, we studied HIV‐infected women receiving ART in a prospective open cohort study in rural Uganda. We used random effects regression models to compare the CD4 counts of women who became pregnant and those who did not, and among the pregnant women before and after pregnancy. CD4 count and proportions with detectable viral load (≥400 copies/ml) were compared between the two groups using the Mann–Whitney rank sum test and logistic regression respectively.

Results  Of 88 women aged 20–40 years receiving ART, 23 became pregnant. At ART initiation, there were no significant differences between those who became pregnant and those who did not in clinical, immunological and virological parameters. Among women who became pregnant, CD4 cell count increased before pregnancy (average 75.9 cells/mm3 per year), declined during pregnancy (average 106.0) but rose again in the first year after delivery (average 88.6). Among women who did not become pregnant, the average CD4 cell count rise per year for the first 3 years was 88.5. There was no significant difference in the proportions of women with detectable viral load at last clinic visit among those who became pregnant (8.7%) and those who did not (16.1%), P = 0.499.

Conclusion  Pregnancy had no lasting effect on the immunological and virological outcomes of HIV‐infected women on ART.
Serological profiles and evaluation of parasitaemia by PCR and blood culture in individuals chronically infected by Trypanosoma cruzi treated with benzonidazole
Authors: Aguiar Camila , Batista Angelica M. , Pavan Tycha B. S. , Almeida Eros A. , Guariento Maria E. , Wanderley Jamiro S. , Costa Sandra C. B.
Published: December 2011

Objective  To evaluate the serological and parasitological status of patients with chronic Chagas disease (CD) after chemotherapy with benzonidazole.

Methods  Retrospective study of patients treated with benzonidazole (5 mg/kg/day for 60 days) between 1980 and 2010. Twenty‐nine patients who had CD confirmed by two reagent immunological tests and/or one positive xenodiagnosis before treatment were included. Conventional serology (ELISA and IIF) and parasitological tests (haemoculture and N‐PCR) were performed.

Results  At the time of treatment, the mean age of patients was 36 ± 7.24 years (20–39 years) and the time post‐treatment varied from 1 to 29 years. After chemotherapy, all individuals had reagent ELISA and 93.1% had positive results for the IIF test. T. cruzi DNA was detected by N‐PCR in 48.3%. Negative results were observed in 41.4% and inconclusive ones in 10.3%. Haemoculture was negative for all individuals.

Conclusions  Our results suggest that N‐PCR may be useful in the early identification of therapeutic failure of CD. Although it is difficult to determine parasitological cure in negative N‐PCR cases, we can infer that this condition represents a declination of parasitaemia as a favourable consequence of aetiological treatment.
Polymorphic variants of the IL2RA gene and susceptibility to type 1 diabetes in the Polish population
Authors: Fichna M. , Żurawek M. , Fichna P. , Januszkiewicz D. , Nowak J.
Published: December 2011

Polymorphic variants of the IL2RA gene, which encodes high‐affinity alpha subunit (CD25) of the interleukin‐2 receptor, were recently found to affect the risk of several autoimmune disorders. This study was aimed to investigate the association of selected IL2RA polymorphisms (rs11594656, rs3118470, rs2104286 and rs7093069) with type 1 diabetes (T1D) in a Polish cohort comprising 445 patients and 671 healthy control subjects. The minor A allele at rs11594656 was found significantly less frequently among T1D subjects, compared with the control group [P = 0.011; odds ratio (OR) = 0.77; 95% confidence interval (CI) = 0.629–0.942]. In contrast, the minor C allele at rs3118470 appeared to be significantly associated with the occurrence of T1D (P = 0.003; OR = 1.30; 95% CI = 1.094–1.550). Two other IL2RA single nucleotide polymorphisms (SNPs) did not show significant differences among investigated groups. In conclusion, the study confirms the association of the IL2RA locus with T1D in the Polish population.
Impaired wake‐promoting mechanisms in ghrelin receptor‐deficient mice
Authors: Esposito Matthew , Pellinen Jacob , Kapás Levente , Szentirmai Éva
Published: December 2011

Ghrelin receptors are expressed by key components of the arousal system. Exogenous ghrelin induces behavioral activation, promotes wakefulness and stimulates eating. We hypothesized that ghrelin‐sensitive mechanisms play a role in the arousal system. To test this, we investigated the responsiveness of ghrelin receptor knockout (KO) mice to two natural wake‐promoting stimuli. Additionally, we assessed the integrity of their homeostatic sleep‐promoting system using sleep deprivation. There was no significant difference in the spontaneous sleep–wake activity between ghrelin receptor KO and wild‐type (WT) mice. WT mice mounted robust arousal responses to a novel environment and food deprivation. Wakefulness increased for 6 h after cage change accompanied by increases in body temperature and locomotor activity. Ghrelin receptor KO mice completely lacked the wake and body temperature responses to new environment. When subjected to 48 h food deprivation, WT mice showed marked increases in their waking time during the dark periods of both days. Ghrelin receptor KO mice failed to mount an arousal response on the first night and wake increases were attenuated on the second day. The responsiveness to sleep deprivation did not differ between the two genotypes. These results indicate that the ghrelin‐receptive mechanisms play an essential role in the function of the arousal system but not in homeostatic sleep‐promoting mechanisms.
The effector and scaffolding proteins AF6 and MUPP1 interact with connexin36 and localize at gap junctions that form electrical synapses in rodent brain
Authors: Li X. , Lynn B. D. , Nagy J. I.
Published: December 2011

Electrical synapses formed by neuronal gap junctions composed of connexin36 (Cx36) occur in most major structures in the mammalian central nervous system. These synapses link ensembles of neurons and influence their network properties. Little is known about the macromolecular constituents of neuronal gap junctions or how transmission through electrical synapses is regulated at the level of channel conductance or gap junction assembly/disassembly. Such knowledge is a prerequisite to understanding the roles of gap junctions in neuronal circuitry. Gap junctions share similarities with tight and adhesion junctions in that all three reside at close plasma membrane appositions, and therefore may associate with similar structural and regulatory proteins. Previously, we reported that the tight junction‐associated protein zonula occludens‐1 (ZO‐1) interacts with Cx36 and is localized at gap junctions. Here, we demonstrate that two proteins known to be associated with tight and adherens junctions, namely AF6 and MUPP1, are components of neuronal gap junctions in rodent brain. By immunofluorescence, AF6 and MUPP1 were co‐localized with Cx36 in many brain areas. Co‐immunoprecipitation and pull‐down approaches revealed an association of Cx36 with AF6 and MUPP1, which required the C‐terminus PDZ domain interaction motif of Cx36 for interaction with the single PDZ domain of AF6 and with the 10th PDZ domain of MUPP1. As AF6 is a target of the cAMP/Epac/Rap1 signalling pathway and MUPP1 is a scaffolding protein that interacts with CaMKII, the present results suggest that AF6 may be a target for cAMP/Epac/Rap1 signalling at electrical synapses, and that MUPP1 may contribute to anchoring CaMKII at these synapses.
AMPA receptor modulation by cornichon‐2 dictated by transmembrane AMPA receptor regulatory protein isoform
Authors: Gill Martin B. , Kato Akihiko S. , Wang He , Bredt David S.
Published: December 2011

Transmembrane AMPA receptor regulatory proteins (TARPs) are auxiliary subunits that modulate AMPA receptor trafficking, gating and pharmacology throughout the brain. Why cornichon‐2 (CNIH‐2), another AMPA receptor‐associated protein, modulates AMPA receptor gating and pharmacology in hippocampal neurons but not cerebellar granule neurons remains unresolved. Here, we report that CNIH‐2 differentially impacts Type‐Ia (γ‐2 or γ‐3) vs. Type‐Ib (γ‐4 or γ‐8) TARP‐containing AMPA receptors. Specifically, with AMPA receptors comprising γ‐2, the cerebellar‐enriched TARP isoform, CNIH‐2 decreases IKA/IGlu ratio and decreases cyclothiazide efficacy while having minimal impact on recovery from desensitization and deactivation kinetics. By contrast, with AMPA receptors comprising γ‐8, the hippocampal‐enriched TARP isoform, we find that CNIH‐2 slows deactivation kinetics, increases cyclothiazide potency and occludes a novel AMPA receptor kinetic phenomenon, namely resensitization. Additionally, we find that CNIH‐2 differentially modulates the glutamate off‐kinetics of γ‐8‐containing, but not γ‐2‐containing, AMPA receptors in a manner dependent upon the duration of agonist application. Together, these data demonstrate that the modulation of AMPA receptors by CNIH‐2 depends upon the TARP isoform composition within the receptor complex.
Striatal NTS1, dopamine D2 and NMDA receptor regulation of pallidal GABA and glutamate release – a dual‐probe microdialysis study in the intranigral 6‐hydroxydopamine unilaterally lesioned rat
Authors: Ferraro Luca , O’Connor William T. , Beggiato Sarah , Tomasini Maria C. , Fuxe Kjell , Tanganelli Sergio , Antonelli Tiziana
Published: December 2011

The current microdialysis study elucidates a functional interaction between the striatal neurotensin NTS1 receptor and the striatal dopamine D2 and N‐methyl‐d‐aspartic acid (NMDA) receptors in the regulation of striatopallidal gamma‐aminobutyric acid (GABA) and glutamate levels after an ipsilateral intranigral 6‐hydroxydopamine‐induced lesion of the ascending dopamine pathways to the striatum. Lateral globus pallidus GABA levels were higher in the lesioned group while no change was observed in striatal GABA and glutamate levels. The 6‐hydroxydopamine‐induced lesion did not alter the ability of intrastriatal NT (10 nm) to counteract the decrease in pallidal GABA and glutamate levels induced by the dopamine D2‐like receptor agonist quinpirole (10 μm). A more pronounced increase in the intrastriatal NMDA‐ (10 μm) induced increase in pallidal GABA levels was observed in the lesioned group while it attenuated the increase in striatal glutamate levels and amplified the increase in pallidal glutamate levels compared with that observed in the controls. NT enhanced the NMDA‐induced increase in pallidal GABA and glutamate and striatal glutamate levels; these effects were counteracted by the NTS1 antagonist SR48692 (100 nm) in both groups. These findings demonstrate an inhibitory striatal dopamine D2 and an excitatory striatal NMDA receptor regulation of striatopallidal GABA transmission in both groups. These actions are modulated by NT via antagonistic NTS1/D2 and facilitatory NTS1/NMDA receptor–receptor interactions, leading to enhanced glutamate drive of the striatopallidal GABA neurons associated with motor inhibition, effects which all are counteracted by SR48692. Thus, NTS1 antagonists in combination with conventional treatments may provide a novel therapeutic strategy in Parkinson’s disease.
Differential effects of brain‐derived neurotrophic factor and neurotrophin‐3 on hindlimb function in paraplegic rats
Authors: Boyce Vanessa S. , Park Jihye , Gage Fred H. , Mendell Lorne M.
Published: December 2011

We compared the effect of viral administration of brain‐derived neurotrophic factor (BDNF) or neurotrophin 3 (NT‐3) on locomotor recovery in adult rats with complete thoracic (T10) spinal cord transection injuries, in order to determine the effect of chronic neurotrophin expression on spinal plasticity. At the time of injury, BDNF, NT‐3 or green fluorescent protein (GFP) (control) was delivered to the lesion via adeno‐associated virus (AAV) constructs. AAV–BDNF was significantly more effective than AAV–NT‐3 in eliciting locomotion. In fact, AAV–BDNF‐treated rats displayed plantar, weight‐supported hindlimb stepping on a stationary platform, that is, without the assistance of a moving treadmill and without step training. Rats receiving AAV–NT‐3 or AAV–GFP were incapable of hindlimb stepping during this task, despite provision of balance support. AAV–NT‐3 treatment did promote the recovery of treadmill‐assisted stepping, but this required continuous perineal stimulation. In addition, AAV–BDNF‐treated rats were sensitized to noxious heat, whereas AAV–NT‐3‐treated and AAV–GFP‐treated rats were not. Notably, AAV–BDNF‐treated rats also developed hindlimb spasticity, detracting from its potential clinical applicability via the current viral delivery method. Intracellular recording from triceps surae motoneurons revealed that AAV–BDNF significantly reduced motoneuron rheobase, suggesting that AAV–BDNF promoted the recovery of over‐ground stepping by enhancing neuronal excitability. Elevated nuclear c‐Fos expression in interneurons located in the L2 intermediate zone after AAV–BDNF treatment indicated increased activation of interneurons in the vicinity of the locomotor central pattern generator. AAV–NT‐3 treatment reduced motoneuron excitability, with little change in c‐Fos expression. These results support the potential for BDNF delivery at the lesion site to reorganize locomotor circuits.
Right–left asymmetry in the cortical processing of sounds for social communication vs. navigation in mustached bats
Authors: Kanwal Jagmeet S.
Published: December 2011

In the Doppler‐shifted constant frequency processing area in the primary auditory cortex of mustached bats,Pteronotus parnellii, neurons respond to both social calls and to echolocation signals. This multifunctional nature of cortical neurons creates a paradox for simultaneous processing of two behaviorally distinct categories of sound. To test the possibility of a stimulus‐specific hemispheric bias, single‐unit responses were obtained to both types of sounds, calls and pulse‐echo tone pairs, from the right and left auditory cortex. Neurons on the left exhibited only slightly higher peak response magnitudes for their respective best calls, but they showed a significantly higher sensitivity (lower response thresholds) to calls than neurons on the right. On average, call‐to‐tone response ratios were significantly higher for neurons on the left than for those on the right. Neurons on the right responded significantly more strongly to pulse‐echo tone pairs than those on the left. Overall, neurons in males responded to pulse‐echo tone pairs with a much higher spike count compared to females, but this difference was less pronounced for calls. Multidimensional scaling of call responses yielded a segregated representation of call types only on the left. These data establish for the first time, a behaviorally directed right–left asymmetry at the level of single cortical neurons. It is proposed that a lateralized cortex emerges from multiparametric integration (e.g. combination‐sensitivity) within a neuron and inhibitory interactions between neurons that come into play during the processing of complex sounds.
Riemann–Hilbert Problems, Matrix Orthogonal Polynomials and Discrete Matrix Equations with Singularity Confinement
Authors: Cassatella‐Contra G.A. , Mañas M.
Published: December 2011

In this paper, matrix orthogonal polynomials in the real line are described in terms of a Riemann–Hilbert problem. This approach provides an easy derivation of discrete equations for the corresponding matrix recursion coefficients. The discrete equation is explicitly derived in the matrix Freud case, associated with matrix quartic potentials. It is shown that, when the initial condition and the measure are simultaneously triangularizable, this matrix discrete equation possesses the singularity confinement property, independently if the solution under consideration is given by the recursion coefficients to quartic Freud matrix orthogonal polynomials or not.
THE APPLICATION OF A PORTABLE X‐RAY FLUORESCENCE SPECTROMETER TO THE ON‐SITE ANALYSIS OF GLASS VESSEL FRAGMENTS FROM SOUTHERN THAILAND*
Authors: TANTRAKARN K. , KATO N. , NAKAI I. , SHINDO Y. , CHAISUWAN B.
Published: December 2011

Ancient glass vessel fragments belonging to the seventh to ninth centuries ad, from the Ko Kho Khao, Laem Pho and Khuan Lukpad sites in southern Thailand, were studied. The glass vessel fragment samples are a collection belonging to the Department of Archaeology, the 15th Regional Office of Fine Arts of Thailand. The chemical compositions of the glasses were analysed using a modified portable energy‐dispersive X‐ray fluorescence spectrometer (OURSTEX 100FA‐II) by the introduction of a MOXTEK® AP3.3 polymer window (5 mm2∅) to the KETEK silicon drift detector for the measurement of light elements. The non‐destructive analysis was performed at the National Museum, Phuket, in Thailand. It is shown that the glass chemical compositions belong to mineral and plant‐ash based soda–lime–silicate glass. The origins of the glass artefacts are discussed in terms of raw materials and glass decoration, and compared with previously reported similar typological glasses from sites in the port city of Rāya and the Monastery of Wadi al‐Tur in Egypt.
The traditional ayurvedic medicine, Eugenia jambolana (Jamun fruit), decreases liver inflammation, injury and fibrosis during cholestasis
Authors: Donepudi Ajay C. , Aleksunes Lauren M. , Driscoll Maureen V. , Seeram Navindra P. , Slitt Angela L.
Published: December 2011

Background

Cholestasis is a common disease of the liver. Chronic cholestasis eventually leads to hepatic cirrhosis and fibrosis, and rodent chronic cholestasis models are used to study aspects of fibrosis and cirrhosis. Cholestasis‐induced liver injury and fibrosis are associated with increased oxidative stress and inflammation. Few pharmacological therapies exist for treatment of cholestasis or cirrhosis, but it is known that humans with better nutritional intake are less likely to develop certain types of cirrhosis. Eugenia jambolana (Jamun) is a tropical berry fruit rich in antioxidant anthocyanin compounds.

Aim

As anthocyanins decrease cellular lipid peroxidation and oxidative stress, it was hypothesized that Jamun fruit extract (JFE) administration could protect against cholestatic liver injury and inflammation in mice.

Method

Starting 24 h after sham or bile‐duct ligation (BDL) surgery, male C57Bl/6 mice were administered vehicle or JFE (100 mg/kg, po) for 10 days.

Results

Mice that underwent BDL had elevated serum ALT levels, which were reduced to 60% by JFE treatment. Likewise, BDL caused hepatic inflammation, macrophage infiltration, fibrosis and necrosis, all of which were largely improved by JFE. Interestingly, hepatoprotection was observed in JFE‐treated BDL mice, despite suppressed transporter expression and increased hepatic bile acid concentrations.

Conclusion

Jamun fruit phytochemicals decreased hepatic inflammation and oxidative stress, and protected against hepatocellular injury in mice. Jamun warrants further investigation as a potential antioxidant/anti‐inflammatory therapy not only to treat cholestasis but also other liver diseases with an inflammatory component.
The potential role of prebiotic fibre for treatment and management of non‐alcoholic fatty liver disease and associated obesity and insulin resistance
Authors: Parnell Jill A. , Raman Maitreyi , Rioux Kevin P. , Reimer Raylene A.
Published: December 2011

Non‐alcoholic fatty liver disease (NAFLD) and the more severe non‐alcoholic steatohepatitis (NASH) represent a spectrum of diseases involving hepatic fat accumulation and histological features essentially identical to alcoholic liver disease; however, they occur in the absence of excessive alcohol intake. They typically arise in conjunction with one or more features of the metabolic syndrome. Lifestyle mediated weight loss remains the primary mode of therapy forNAFLDandNASH, but this is often ineffective and adjunctive medical and surgical treatments are presently lacking. Prebiotic fibres are a group of non‐digestible carbohydrates that modulate the human microbiota in a manner that is advantageous to host health. Rodent studies suggest that dietary supplementation with prebiotic fibres positively impactsNAFLDby modifying the gut microbiota, reducing body fat, and improving glucoregulation. Future research should focus on placebo‐controlled, human, clinical trials using histological endpoints to address the effects of prebiotics onNAFLDandNASH. The aim of this review is to summarize current knowledge about prebiotics as an emerging therapeutic target forNAFLD.
Hepatocellular carcinoma and survival in patients with autoimmune hepatitis (Japanese National Hospital Organization‐autoimmune hepatitis prospective study)
Authors: Migita Kiyoshi , Watanabe Yukio , Jiuchi Yuka , Nakamura Yoko , Saito Akira , Yagura Michiyasu , Ohta Hajime , Shimada Masaaki , Mita Eiji , Hijioka Taizo , Yamashita Haruhiro , Takezaki Eiichi , Muro Toyokichi , Sakai Hironori , Nakamuta Makoto , Abiru Seigo , Komori Atsumasa , Ito Masahiro , Yatsuhashi Hiroshi , Nakamura Minoru , Ishibashi Hiromi ,   the Japanese NHO‐Liver‐network study group
Published: December 2011

Background/Aims

Although the outcome of autoimmune hepatitis (AIH) is generally good, the natural course and likelihood of progression to cirrhosis or hepatocellular carcinoma (HCC) remain undefined, and may vary by region and population structure. Our aims were to evaluate risk factors that contribute to poor outcome and particularly development of HCC in a prospective multicentric cohort study of AIH.

Methods

The study group comprised 193 Japanese patients with AIH who were prospectively followed up at annual intervals between 1995 and 2008. The mean follow‐up period was 8.0 ± 4.5 years.

Results

Twenty‐one (10.9%) patients had cirrhosis at presentation and a further 15 (7.8%) developed cirrhosis during the follow‐up period. Survival rates were 94.2% at 10 years and 89.3% at 15 years. HCC was diagnosed in seven of the 193 patients. The presence of cirrhosis at presentation was a risk factor for HCC according to a Cox proportional hazard model, and the HCC‐free survival rate was significantly lower in those with cirrhosis compared to those without cirrhosis according to Kaplan–Meier analysis.

Conclusions

Although the outcome of AIH is as good if not better among Japanese than for other populations, there was an increased risk of HCC in these patients. Cirrhosis at presentation was predictive of development of HCC in AIH in Japan.
Propagation of cutaneous thermal injury: A mathematical model
Authors: Xue Chuan , Chou Ching‐Shan , Kao Chiu‐Yen , Sen Chandan K. , Friedman Avner
Published: December 2011

Cutaneous burn wounds represent a significant public health problem with 500,000 patients per year in the USA seeking medical attention. Immediately after skin burn injury, the volume of the wound burn expands due to a cascade of chemical reactions, including lipid peroxidation chain reactions. Such expansion threatens life and is therefore highly clinically significant. Based on these chemical reactions, the present paper develops for the first time a three‐dimensional mathematical model to quantify the propagation of tissue damage within 12 hours post initial burn. We use the model to investigate the effect of supplemental antioxidant vitamin E for intercepting propagation. We show, for example, that if tissue levels of vitamin E tocotrienol are increased, postburn, by five times then this would slow down the lipid peroxide propagation by at least 50%. We chose the alpha‐tocotrienol form of vitamin E as it is a potent inhibitor of 12‐lipoxygenase, which is known to propagate oxidative lipid damage. Our model is formulated in terms of differential equations, and sensitivity analysis is performed on the parameters to ensure the robustness of the results.
Inverse Gottron’s Papules: An Unusual Cutaneous Manifestation of Juvenile Dermatomyositis
Authors: Quinter Suzanne D. , Chiu Yvonne E. , Lyon Valerie B. , Holland Kristen E. , Ruggeri Sun Young , Drolet Beth A.
Published: December 2011

Abstract:  Dermatomyositis is an autoimmune inflammatory myopathy characterized by unique cutaneous features. Gottron’s papules are pathognomonic, lichenoid papules that can be found overlying the joints of the dorsal hand. Papules on the palms of the hand are less commonly seen, especially in the pediatric age group. Recognition of these inverse Gottron’s papules as a sign of dermatomyositis is important as they may be the only cutaneous feature and may be a clue of underlying interstitial lung disease.
Congenital Erosive and Vesicular Dermatosis: A New Case and Review of the Literature
Authors: Mashiah Jacob , Wallach Daniel , Leclerc‐Mercier Stéphanie , Bodemer Christine , Hadj‐Rabia Smaïl
Published: December 2011

Abstract:  Congenital erosive and vesicular dermatosis is a rare syndrome first described by Cohen et al in 1985. Most of the 18 cases published have been reported in premature newborns. Affected babies typically present with erosions and vesicles that tend to heal shortly after birth with reticulated scaring. We report an additional case, followed up for 5 years, in which we excluded a pathogenic mutation in the TP63 gene.
Outcomes in Pediatric Atypical Spitz Tumors Treated Without Sentinel Lymph Node Biopsy
Authors: Cerrato Felecia , Wallins Joseph S. , Webb Michelle L. , McCarty Erika R. , Schmidt Birgitta A. , Labow Brian I.
Published: December 2011

Abstract:  The diagnosis of atypical Spitz tumor (AST) in a pediatric patient conveys an uncertain potential for malignancy. Although pediatric melanoma is rare, AST may be treated aggressively with sentinel lymph node biopsy (SLNB) and subsequent completion lymphadenectomy. These procedures have unclear therapeutic benefit and potential morbidity. We aimed to collect outcomes on children with AST treated with excision alone to assist in the management of these lesions. We queried our institution’s pathology database for AST specimens submitted between 1994 and 2009. A dermatopathologist reviewed pathology slides to confirm AST diagnosis. Clinical information was obtained from medical records, and outcomes surveys were administered to children with AST. Twenty‐nine patients met AST diagnostic criteria and were included in this study. Mean age at first excision was 9.0 ± 4.2 (range 2.3–17.5), and 19 patients underwent more than one excision procedure to achieve clear margins. No patient had SLNB. Fourteen patients (48%) with mean follow‐up time of 8.4 years (range 3.5–15.8) completed clinical outcomes surveys. Outcomes with mean follow‐up time of 2.8 years (range 0.02–8.1 years) were obtained for 10 additional patients from medical records. There were no reports of recurrence, additional lesions, or metastases in these 24 patients. We report one of the largest series of children with AST treated using excision alone and who remain disease free after a significant follow‐up period. Our data suggest that SLNB is not warranted in the routine management of pediatric AST. We recommend complete excision with clear margins and careful clinical follow‐up.
Human platelet concentrates: a source of solvent/detergent‐treated highly enriched brain‐derived neurotrophic factor
Authors: Burnouf Thierry , Kuo Ya‐Po , Blum David , Burnouf Sylvie , Su Chen‐Yao
Published: December 2011

BACKGROUND: Human blood platelets (PLTs) contain brain‐derived neurotrophic factor (BDNF), a neurotrophin that binds to neurotrophic tropomyosin‐related kinase B (TrkB) receptor on central nervous system cells. This binding promotes neural synaptic plasticity and memory and prevents neuronal degeneration. Alterations in BDNF homeostasis are associated with aging and are found in several neurodegenerative conditions such as Alzheimer's, Huntington's, and Parkinson's diseases and multiple sclerosis. We have developed PLT viral inactivation and chromatographic fractionation processes and decided here to identify fractions enriched in BDNF.

STUDY DESIGN AND METHODS: PLT concentrates (PCs) were treated by solvent/detergent (S/D), extracted by oil, and subjected to fractionation (C18, sulfopropyl [SP]‐Sepharose, diethylaminoethyl [DEAE]‐Sepharose, or activated charcoal). BDNF and pro‐BDNF were evaluated by enzyme‐linked immunosorbent assay, and Western blot. TrkB was studied by Western blot. Tri‐n‐butyl phosphate (TnBP) was quantified by high‐performance liquid chromatography, and Triton X‐45 by gas chromatography.

RESULTS: The mean BDNF content of 2.9 ± 0.7 ng/mL in PC was noted to increase to 56.2 ± 2.4 ng/mL after S/D treatment and remained stable during oil extraction. Approximately 70% of the BDNF content was recovered after C18 chromatography. BDNF did not bind to DEAE‐Sepharose and was almost completely adsorbed by charcoal. Chromatography on SP‐Sepharose yielded a highly enriched 13‐kDa mature BDNF fraction that was more than 170‐fold purified, with a mean of 137 ± 29.4 ng/mL and 82% chromatographic recovery, devoid of detectable TnBP and Triton X‐45. Pro‐BDNF and TrkB proteins were not detected in the PLT extracts.

CONCLUSION: We obtained a S/D‐treated, highly enriched mature PLT‐derived BDNF fraction that could help unveil the pharmacokinetics, pharmacodynamic, and potential therapeutic applications of the BDNF neurotrophin.
Cost‐effectiveness of using recombinant activated factor VII as an off‐label rescue treatment for critical bleeding requiring massive transfusion
Authors: Ho Kwok M. , Litton Edward
Published: December 2011

BACKGROUND: Recombinant activated factor VII (rFVIIa) is widely used as an off‐label rescue treatment for patients with nonhemophilic critical bleeding.

STUDY DESIGN AND METHODS: Using data from the intensive care unit, transfusion service, and death registry, the long‐term survival after using rFVIIa and the associated cost per life‐year gained in a consecutive cohort of patients with critical bleeding requiring massive transfusion (≥10 red blood cell [RBC] units in 24 hr) were assessed. rFVIIa was only used as a lifesaving treatment when conventional measures had failed.

RESULTS: Of the 353 patients with critical bleeding requiring massive transfusion, 81 (23%) required rFVIIa as a lifesaving rescue treatment. The patients requiring rFVIIa received a greater number of transfusions (number of units: RBCs, 18 vs. 12; fresh‐frozen plasma, 16 vs. 10; platelets, 4 vs. 2; p < 0.001) and had a shorter survival time (24 months vs. 33 months; p = 0.002) than those who did not require rFVIIa. The total cost per life‐year gained of massive transfusion and incremental cost of rFVIIa as a lifesaving treatment were US$1,148,000 (£711,760; 95% confidence interval [CI], US$825,000‐US$1,471,000) and US$736,000 (£456,320; 95% CI, US$527,000‐US$945,000), respectively. The incremental costs of rFVIIa increased with severity of illness and transfusion requirement and were greater than the usual acceptable cost‐effective limit (<US$100,000 per life‐year) for most patients with critical bleeding.

CONCLUSIONS: As a lifesaving treatment for critical bleeding, the incremental cost of rFVIIa was high. Careful patient selection is critical to balance the potential benefits of rFVIIa in an individual patient against the cost to the community.
Exploratory in vitro study of red blood cell storage containers formulated with an alternative plasticizer
Authors: Dumont Larry J. , Baker Sharry , Dumont Deborah F. , Herschel Louise , Waters Susan , Calcagni Kristin , Sandford Craig , Radwanski Katherine , Min Kyungyoon , David Raymond M. , Otter Rainer
Published: December 2011

BACKGROUND: The plasticizer di‐2‐ethylhexyl phthalate (DEHP) is a common component in medical plastics. There is motivation to replace this component; however, DEHP is necessary to prevent excessive hemolysis in stored red blood cells (RBCs). Our objective is to evaluate a candidate replacement plasticizer (Hexamoll, di‐isononyl cyclohexane‐1,2‐dicarboxylic acid [DINCH], BASF Corp.) compared to DEHP in an in vitro feasibility study. We hypothesize that the candidate will provide at least equivalent protection against hemolysis for RBCs stored for 42 days and periodic mixing of RBCs will add additional protection against hemolysis.

STUDY DESIGN AND METHODS: Whole blood was collected into citrate‐phosphate‐dextrose; combined into pools of 2 ABO identical whole blood units; and divided, leukoreduced, centrifuged, and separated into plasma and RBCs. Additive solution was added, and the RBCs were stored for 42 days at 1 to 6°C. In three parts of this study, split pools were paired as DINCH‐polyvinyl chloride (PVC) with weekly mixing versus DINCH‐PVC with no mixing, DINCH‐PVC mixed versus DEHP‐PVC no mix, and DINCH‐PVC versus DEHP‐PVC with neither mixed. A standard panel of in vitro RBC characteristics was determined on Days 0 and 42.

RESULTS: Mixing DINCH‐PVC weekly improved Day 42 hemolysis (0.36 ± 0.07% vs.0.56 ± 0.15%, p = 0.002), and mixed DINCH‐PVC bags were noninferior to unmixed DEHP‐PVC bags (p ≤ 0.05). DINCH‐PVC bags stored without weekly mixing were inferior to unmixed DEHP‐PVC bags for hemolysis on Day 42, although no individual bag exceeded 0.8% hemolysis.

CONCLUSION: Periodic mixing of RBCs stored in DINCH‐PVC provides additional protection against hemolysis. Unmixed DINCH‐PVC bags were inferior to DEHP‐PVC bags for prevention of hemolysis, but remain a candidate for replacement DEHP in RBC storage bags.
Direct Observation of a Screw Dislocation Normal to the Beam by Z‐Contrast STEM
Authors: Li Fangzhi , Nian Hongqiang , Du Kui , Wang Jiemin , Wang Jingyang , Zhou Yanchun
Published: December 2011

Dislocation core structures in metals and ceramics are long‐standing questions in materials research. Detailed knowledge about core structure of screw dislocations remains a major challenge. We have designed and synthesized a novel HfAl4C4 ceramic with a large c axis and vast difference in atomic numbers, in which a c[0001] screw dislocation is directly observed with dislocation line perpendicular to the viewing direction by STEM. This observation has cast a new light on revealing the detailed core structure of screw dislocations.
Light Reflection Behavior of ZrB2‐Based Composites with SiC Particles
Authors: Ikegami Masahide , Guo Shuqi , Matsumura Katsunori , Kagawa Yutaka
Published: December 2011

The light reflection behavior of ZrB2‐based composites with SiC particles was examined in the infrared wavelength range of 1.5–20 μm and at room temperature. Effects of the amount and size of SiC particles on light reflection behavior were evaluated. The results showed that the light reflection behavior of the composites was closely linked with the light absorption of the added SiC particles, in absence of light scattering from the SiC particles. In addition, the light reflectance of the composites depended on the amount and size of the SiC particles. Increase in the amount and size of the SiC particles led to decrease in the light reflectance of the composites.
The Effect of Processing Conditions on the Properties ofLTCCMaterial
Authors: Makarovič Kostja , Meden Anton , Hrovat Marko , Holc Janez , Benčan Andreja , Dakskobler Aleš , Kosec Marija
Published: December 2011

In this work the effect of firing temperature and firing time on the phase composition, microstructure, biaxial flexural strength, and temperature coefficient of expansion (TCE) of low‐temperature cofired ceramic (LTCC) material is presented. At temperatures around 700°C theAl2O3starts to dissolve in a low viscosity glass phase and this takes place up to 800°C, when 10 wt% ofAl2O3ceramic filler is dissolved in the glass phase forming the alumina‐enriched area. This area is suitable for the crystallization of anorthite, which nucleates on theAl2O3particles. The crystallization starts at 875°C and the mass fraction of anorthite increases with increasing temperature until it reaches a plateau value of around 22 wt% at higher temperatures or longer firing times. The biaxial flexural strength of theLTCCincreases with increasing firing temperature from 135 MPa (at 800°C) to around 300 MPa (at 900°C). The major effect on the biaxial flexural strength ofLTCCis that of porosity. The effect of the amount of anorthite on theLTCCbiaxial flexural strength is minor. TheTCEof theLTCCdecreases from 5.6 × 10−6to 5.0 × 10−6 K−1with increasing firing temperatures or times and it is correlated with the anorthite mass fraction, which crystallizes at the expense of a decreasing amount of glass phase in theLTCC.
Nanocomposite Ti–Si–N Coatings Deposited by Reactive dc Magnetron Sputtering for Biomedical Applications
Authors: Balasubramanian Subramanian , Ramadoss Ananthakumar , Kobayashi Akira , Muthirulandi Jayachandran
Published: December 2011

Nanocomposite Ti–Si–N coatings were prepared by reactive dc magnetron sputtering in a mixture of Ar and N2 gases onto bio implantable 316L stainless steel substrates. X‐ray diffraction analysis revealed that the Ti–Si–N nanocomposite coatings are mainly composed of amorphous Si3N4 and TiN crystals. The presence of different phases like TiN, TiO2, and Si3N4 was confirmed from X‐ray photoelectron spectroscopy analysis. Raman spectra of the as‐deposited composite coatings exhibited characteristic peaks at 207.5, 305.8, 442.5, and 571.8 cm−1. HRTEM indicated columnar microstructure. A higher hardness value of 35 GPa for the nanocomposite coatings was observed. The potentiodynamic polarization and electrochemical impedance spectroscopy measurements showed that the Ti–Si–N nanocomposite coatings exhibited superior corrosion resistance compared with the Si3N4, TiN single layer, and the bare substrate in simulated body fluid solution.
Multicenter Study of Safety in Stenting for Symptomatic Vertebral Artery Origin Stenosis: Results from the Society of Vascular and Interventional Neurology Research Consortium
Authors: Edgell Randall C. , Zaidat Osama O. , Gupta Rishi , Abou‐Chebl Alex , Linfante Italo , Xavier Andrew , Nogueira Raul , Alshekhlee Amer , Kalia Jundaid , Etezadi Vahid , Aghaebrahim Nima , Jovin Tudor
Published: December 2011

PURPOSE

To assess the safety and efficacy of vertebral artery origin angioplasty and stenting for stroke prevention in a multicenter clinical experience.

METHODS

Patients with symptomatic vertebral artery origin stenosis (VAOS) were gathered from the Society of Vascular and Interventional Neurology Research Consortium. Demographic, clinical, and procedural data were collected. The main outcome measure was procedural and peri‐procedural risks of stroke, transient ischemic attack (TIA), or death at 1 and 3 months. Logistic regression analysis was used to assess covariates associated with future restenosis.

RESULTS

A total of 148 patients were included with mean age of 66.2 ± 11.5; 74% men and 77% Caucasian. One patient (.8%) had a stroke at 1 month and 5 of 96 (5.2%) patients had TIA at 3 months. There were no immediate procedural events or deaths. The mean angiographic pre‐treatment stenosis was 80.5 ± 12.7%, which was reduced to 5.3 ± 9.1% after stent deployment. Follow‐up angiography showed 15.5% of patients had significant restenosis (≥50%). Predictors of restenosis included age (OR 3.08; 95% CI 1.01, 9.41) and smoking (OR 3.10; 95% CI 1.12, 8.64).

CONCLUSIONS

Endovascular intervention of VAOS is associated with low peri‐procedural complication rates. Restenosis remains a concern; age and smoking predicted future restenosis.