bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic diversity of novel circular ssDNA viruses in bats in China
Authors: Ge Xingyi , Li Jialu , Peng Cheng , Wu Lijun , Yang Xinglou , Wu Yongquan , Zhang Yunzhi , Shi Zhengli
Published: July 2011

Novel circular ssDNA genomes have recently been detected in animals and in the environment using metagenomic and high-throughput sequencing approaches. In this study, five full-length circular ssDNA genomes were recovered from bat faecal samples using inverse PCR with sequences designed based on circovirus-related sequences obtained from Solexa sequencing data derived from a random amplification method. These five sequences shared a similar genomic organization to circovirus or the recently proposed cyclovirus of the family Circoviridae. The newly obtained circovirus/cyclovirus-like genomes ranged from 1741 to 2177 bp, and each consisted of two major ORFs, ORF1 and ORF2, encoding putative replicase (Rep) and capsid (Cap) proteins, respectively. The potential stem–loop region was predicted in all five genomes, and three of them had the typical conserved nonanucleotide motif of cycloviruses. A set of primers targeting the conserved Rep region was designed and used to detect the prevalence of circovirus/cyclovirus sequences in individual bats. Among 199 samples tested, 47 were positive (23.6 %) for the circovirus genome and two (1.0 %) were positive for the cyclovirus genome. In total, 48 partial Rep sequences plus the five full-length genomes were obtained in this study. Detailed analysis indicated that these sequences are distantly related to known circovirus/cyclovirus genomes and may represent 22 novel species that belong to the family Circoviridae.
Trans genomic capture and sequencing of primate exomes reveals new targets of positive selection
Authors: George Renee D. , McVicker Graham , Diederich Rachel , Ng Sarah B. , MacKenzie Alexandra P. , Swanson Willie J. , Shendure Jay , Thomas James H.
Published: July 2011

Comparison of protein-coding DNA sequences from diverse primates can provide insight into these species' evolutionary history and uncover the molecular basis for their phenotypic differences. Currently, the number of available primate reference genomes limits these genome-wide comparisons. Here we use targeted capture methods designed for human to sequence the protein-coding regions, or exomes, of four non-human primate species (three Old World monkeys and one New World monkey). Despite average sequence divergence of up to 4% from the human sequence probes, we are able to capture ∼96% of coding sequences. Using a combination of mapping and assembly techniques, we generated high-quality full-length coding sequences for each species. Both the number of nucleotide differences and the distribution of insertion and deletion (indel) lengths indicate that the quality of the assembled sequences is very high and exceeds that of most reference genomes. Using this expanded set of primate coding sequences, we performed a genome-wide scan for genes experiencing positive selection and identified a novel class of adaptively evolving genes involved in the conversion of epithelial cells in skin, hair, and nails to keratin. Interestingly, the genes we identify under positive selection also exhibit significantly increased allele frequency differences among human populations, suggesting that they play a role in both recent and long-term adaptation. We also identify several genes that have been lost on specific primate lineages, which illustrate the broad utility of this data set for other evolutionary analyses. These results demonstrate the power of second-generation sequencing in comparative genomics and greatly expand the repertoire of available primate coding sequences.
Biphasic Gene Expression Changes Elicited byPhakopsora pachyrhiziin Soybean Correlate with Fungal Penetration and Haustoria Formation
Authors: Schneider Katherine T. , van de Mortel Martijn , Bancroft Timothy J. , Braun Edward , Nettleton Dan , Nelson Rex T. , Frederick Reid D. , Baum Thomas J. , Graham Michelle A. , Whitham Steven A.
Published: July 2011

Inoculation of soybean (Glycine max) plants with Phakopsora pachyrhizi, the causal organism of Asian soybean rust, elicits a biphasic response characterized by a burst of differential gene expression in the first 12 h. A quiescent period occurs from 24 to 48 h after inoculation, in which P. pachyrhizi continues to develop but does not elicit strong host responses, followed by a second phase of intense gene expression. To correlate soybean responses with P. pachyrhizi growth and development, we inoculated the soybean cultivar Ankur (accession PI462312), which carries the Rpp3 resistance gene, with avirulent and virulent isolates of P. pachyrhizi. The avirulent isolate Hawaii 94-1 elicits hypersensitive cell death that limits fungal growth on Ankur and results in an incompatible response, while the virulent isolate Taiwan 80-2 grows extensively, sporulates profusely, and produces a compatible reaction. Inoculated leaves were collected over a 288-h time course for microarray analysis of soybean gene expression and microscopic analysis of P. pachyrhizi growth and development. The first burst in gene expression correlated with appressorium formation and penetration of epidermal cells, while the second burst of gene expression changes followed the onset of haustoria formation in both compatible and incompatible interactions. The proliferation of haustoria coincided with the inhibition of P. pachyrhizi growth in the incompatible interaction or the beginning of accelerated growth in the compatible interaction. The temporal relationships between P. pachyrhizi growth and host responses provide an important context in which to view interacting gene networks that mediate the outcomes of their interactions.
Compulsive use of dopamine replacement therapy: a model for stimulant drug addiction?
Authors: Ambermoon Polly , Carter Adrian , Hall Wayne , Dissanayaka Nadeeka , O'Sullivan John
Published: July 2011

The compulsive use of dopamine replacement therapy (DRT) or dopamine dysregulation syndrome (DDS) is one of the behavioural disturbances reported in some patients with Parkinson's disease (PD) and other disorders who are receiving DRT. We draw this phenomenon to the attention of the addiction field as a topic deserving of more systematic study. We outline: the clinical features, epidemiology and clinical correlates of the disorder; the unresolved issues in its definition and diagnosis; and its potential relevance to neurobiological models of psychostimulant addiction. We argue that compulsive DRT use may provide a useful model for drug addiction, while advancing our understanding of the neurobiology of addiction and improving the management of PD patients with the disorder.
Isolation and characterization of a novel short peptide associated with Crohn's disease
Authors: Mitsuyama K , Niwa M , Masuda J , Kuwaki K , Yamasaki H , Takedatsu H , Kobayashi T , Sata M
Published: July 2011

Phage display technology has been utilized to select target molecules against circulating antibodies. The aims of this study were to isolate a peptide that binds with serum from Crohn's disease (CD) patients and to examine its diagnostic and pathogenic significance. A phage display library was constructed using cDNA from Caco-2 cells. Affinity selection using this cDNA library and serum samples from patients with CD was then performed. Phage clones that specifically reacted with the CD sera were then selected using a phage enzyme-linked immunosorbent assay (ELISA). After the DNA sequences of the selected phages were determined and converted to amino acid sequences, the synthesized peptides were examined using an ELISA. The effect of the synthesized peptides on cytokine release from cultured blood mononuclear cells was investigated. An ELISA analysis for TCP-353 demonstrated that while 61·7% of the samples from CD patients were seroreactive, seroreactivity was less common among patients with ulcerative colitis (7·3%), acute colitis (0%) or colon cancer (11·4%) and among normal subjects (2·8%). The induction of interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α release, but not IL-10 release, in response to TCP-353 peptide was enhanced in CD mononuclear cells only. We isolated a novel peptide that specifically binds to CD sera and stimulates the proinflammatory responses of CD mononuclear cells. TCP-353 may have diagnostic, pathogenic and therapeutic significance with regard to the treatment of CD.
Enhancement of B‐cell receptor signaling by a point mutation of adaptor protein 3BP2 identified in human inherited disease cherubism
Authors: Ogi Kazuhiro , Nakashima Kenji , Chihara Kazuyasu , Takeuchi Kenji , Horiguchi Tomoko , Fujieda Shigeharu , Sada Kiyonao
Published: July 2011

Tyrosine phosphorylation of adaptor protein c‐Abl‐Src homology 3 (SH3) domain‐binding protein‐2 (3BP2, also referred to SH3BP2) positively regulates the B‐cell antigen receptor (BCR)‐mediated signal transduction, leading to the activation of nuclear factor of activated T cells (NFAT). Here we showed the effect of the proline to arginine substitution of 3BP2 in which is the most common mutation in patients with cherubism (P418R) on B‐cell receptor signaling. Comparing to the wild type, overexpression of the mutant form of 3BP2 (3BP2‐P416R, corresponding to P418R in human protein) enhanced BCR‐mediated activation of NFAT. 3BP2‐P416R increased the signaling complex formation with Syk, phospholipase C‐γ2 (PLC‐γ2), and Vav1. In contrast, 3BP2‐P416R could not change the association with the negative regulator 14‐3‐3. Loss of the association mutant that was incapable to associate with 14‐3‐3 could not mimic BCR‐mediated NFAT activation in Syk‐deficient cells. Moreover, BCR‐mediated phosphorylation of extracellular signal regulated kinase (ERK) and c‐Jun N‐terminal kinase (JNK) was not affected by P416R mutation. These results showed that P416R mutation of 3BP2 causes the gain of function in B cells by increasing the interaction with specific signaling molecules.
Simple prediction of crude protein content in vegetation growing on abandoned cultivated land
Authors: Tsutsumi M. , Takahashi Y. , Emoto S. , Ito N. , Sahara S. , Yoshimura T. , Watanabe T.
Published: July 2011

The accuracy of two simple methods was compared for the prediction of crude protein (CP) content of above‐ground plant material of mixed‐species composition on abandoned cultivated land in Japan. The first method is based on standard CP values (in g kg−1 dry matter) for individual species (STV method) as listed in the literature. The second procedure (GLM method) was an application of the generalized linear model using the relative above‐ground biomass of monocots and legumes, total herbage mass, and day of year. Predictions were made at the quadrat scale, and for surveyed sites based on average of values for five or six quadrats in a single survey. A ‘leave‐site‐out’ method was adopted for model validation of the generalized linear model. The observed values of CP content ranged between 21·5 and 161·9 g kg−1 dry matter (DM). With the STV method, the values of root mean square error (RMSE indicates average estimation error) were 50·9 at the quadrat level and 53·8 at the surveyed‐site level (both g kg−1 DM). When a ‘leave‐site‐out’ validation was carried out, the RMSE‐values for the GLM method were 23·2 at the quadrat level and 13·2 at the surveyed‐site level (both g kg−1 DM). We therefore propose adoption of the GLM method for the purpose of estimating the CP content in herbage on abandoned sites.
Identification and expression analysis of nervous wreck, which is preferentially expressed in the brain of the male silkworm moth, Bombyx mori
Authors: Kiya T. , Iwami M.
Published: July 2011

Sexually dimorphic neural circuits are essential for reproductive behaviour. The molecular basis of sexual dimorphism in the silkworm moth (Bombyx mori) brain, however, is unclear. We conducted cDNA subtraction screening and identified nervous wreck (Bmnwk), a synaptic growth regulatory gene, whose expression is higher in the male brain than in the female brain of the silkworm. Bmnwk was preferentially expressed in the brain at the late pupae and adult stages. In situ hybridization revealed that Bmnwk is highly expressed in the optic lobe of the male moth brain. These findings suggest that Bmnwk has a role in the development and/or maintenance of the optic lobe in the male silkworm brain.
The role of medicine in the decline of post‐War infant mortality in Japan
Authors: Yorifuji Takashi , Tanihara Shinichi , Inoue Sachiko , Takao Soshi , Kawachi Ichiro
Published: July 2011

Yorifuji T, Tanihara S, Inoue S, Takao S, Kawachi I. The role of medicine in the decline of post‐War infant mortality in Japan. Paediatric and Perinatal Epidemiology 2011; 25: 601–608.

The infant mortality rate (IMR) in Japan declined dramatically in the immediate post‐War period (1947–60) in Japan. We compared the time trends in Growth Domestic Product (GDP) in Japan against declines in IMR. We then conducted a prefecture‐level ecological analysis of the rate of decline in IMR and post‐neonatal mortality from 1947 to 1960, focusing on variations in medical resources and public health strategies. IMR in Japan started to decline after World War II, even before the era of rapid economic growth and the introduction of a universal health insurance system in the 1960s. The mortality rates per 1000 infants in 2009 were 2.38 for IMR, 1.17 for neonatal mortality and 1.21 for post‐neonatal mortality. The rate of decline in IMR and preventable IMR (PIMR) during the post‐War period was strongly correlated with prefectural variations in medical resources (per capita physicians, nurses, and proportion of in‐hospital births). The correlation coefficients comparing the number of physicians in 1955 with the declines in IMR and PIMR from 1947 to 1960 were 0.46 [95% confidence interval (CI) 0.19, 0.66] and 0.39 [95% CI 0.11, 0.61], respectively. By contrast, indicators of public health strategies were not associated with IMR decline. The IMR in Japan has been decreasing and seems to be entering a new era characterised by lower neonatal compared with post‐neonatal mortality. Furthermore, the post‐War history of Japan illustrates that improvement in infant mortality is attributable to the influence of medical care, even in the absence of rapid economic development.
Trichinella spiralis antigens prime mixed Th1/Th2 response but do not induce de novo generation of Foxp3+ T cells in vitro
Authors: ILIC N. , WORTHINGTON J. J. , GRUDEN‐MOVSESIJAN A. , TRAVIS M. A. , SOFRONIC‐MILOSAVLJEVIC L. , GRENCIS R. K.
Published: July 2011

Many parasitic helminth infections induce Th2‐type immune responses and engage the regulatory network. In this study, we specifically investigated the influence of antigens derived from different life stages of the helminth Trichinella spiralis on the polarization of naive CD4+ T cells by dendritic cells. Results obtained from C57BL/6 mice showed that T. spiralis derived antigens have the capacity to induce bone marrow‐derived dendritic cells to acquire an incompletely mature phenotype that promotes a significant proliferation of naive CD4+ T cells and a mixed Th1/Th2 cytokine profile with the predominance of Th2 cytokines. Increased production of IL‐4, IL‐9, IL‐10 and IL‐13 accompanied increased IFN‐γ. Furthermore, dendritic cells pulsed with T. spiralis antigens did not induce an increase in the population of Foxp3+ T regulatory cells. Although other helminth antigens have demonstrated the capacity to induce de novo generation of Foxp3+ T regulatory cells, here our in vitro studies provide no evidence that T. spiralis antigens have this capacity.
Attempts to immunize sheep against Teladorsagia circumcincta using fourth‐stage larval extracts
Authors: HALLIDAY A. M. , SMITH W. D.
Published: July 2011

A ConcanavilinA (ConA)‐binding fraction of a detergent‐soluble membrane extract from Teladorsagia circumcincta (formerly Ostertagia circumcincta) fourth‐stage larvae was isolated, and two vaccine trials were conducted with this preparation in groups of 7 worm‐free sheep. All groups were challenged with a total of 5000 T. circumcincta larvae from 1 week after the final immunization and protection assessed by comparing the egg and worm counts, and length of developing worms, of the immunized groups with their respective controls. Immunization with the ConA‐binding antigen induced high‐titre serum antibody responses in both trials. However, no significant reduction in either egg count or worm burdens was observed in the vaccinated groups in either trial. It was concluded that detergent‐soluble, ConA‐binding extracts prepared from T. circumcincta fourth‐stage larvae did not contain significantly protective antigens, despite the fact that an extract prepared in a similar manner from Ostertagia ostertagi had previously significantly protected calves against homologous challenge.
Lithosphere density model in Italy: no hint for slab pull
Authors: Brandmayr Enrico , Marson Iginio , Romanelli Fabio , Panza Giuliano Francesco
Published: July 2011

Terra Nova, 23, 292–299, 2011

The lithosphere–asthenosphere system of the Italic region in terms of shear‐velocity and density distribution with depth is suitable to investigate the geodynamic context of the region. The velocity structure is obtained through nonlinear inversion of dispersion curves compiled from surface wave tomography on cells 1° × 1° and a smoothing optimization method to choose the representative cellular model, whose layering is used as fixed (a priori) information to obtain a density model by means of linear inversion of gravimetric data. Seismicity and heat flow are used as independent constraints in outlining both the crustal and the seismic lid thickness; the nonlinear moment tensor inversion of recent damaging earthquakes allows some insight in the ongoing kinematic processes. Asymmetry between west‐directed (Apennines) and east‐directed (Alps, Dinarides) subductions is a robust feature of the velocity model, while density model reveals that slabs are not denser than the ambient mantle, thus supplies no evidence for slab pull.
Weed flora in paved areas in relation to environment, pavement characteristics and weed control
Authors: FAGOT M , DE CAUWER B , BEELDENS A , BOONEN E , BULCKE R , REHEUL D
Published: July 2011

Fagot M, De Cauwer B, Beeldens A, Boonen E, Bulcke R & Reheul D (2011). Weed flora in paved areas in relation to environment, pavement characteristics and weed control. Weed Research51, 650–660.

By 2015, all herbicide use on public pavements in Flanders (northern region of Belgium) will be phased out. Currently, little is known about weed flora in these pavements or their interactions with different weed control methods. The objectives of this study were to explore the species composition of pavements in relation to various abiotic factors and applied weed control methods. A vegetation survey was conducted on 163 public pavements constructed with small paving elements across Flanders. Botanical composition was determined, and a score for street scene perception was calculated. For each pavement, a set of environmental conditions and technical characteristics was determined, and data on the applied weed control methods were collected. Apart from Musci (mosses), the most important plant species were Poa annua, Sagina procumbens, Conyza canadensis, Taraxacum officinale and Plantago major. Weed species composition and street scene perception were affected by intensity of use, joint width and light intensity. Weed prevention measures may be built into the construction of pavements by manipulating light, joints and use in their design. Repeated use of a single weed control method caused shifts in weed flora. This suggests that more optimal weed control on pavements is likely to be achieved by alternating weed control methods.
The antiproliferative function of violacein‐like purple violet pigment (PVP) from an Antarctic Janthinobacterium sp. Ant5‐2 in UV‐induced 2237 fibrosarcoma
Authors: Mojib Nazia , Nasti Tahseen H. , Andersen Dale T. , Attigada Venkatram R. , Hoover Richard B. , Yusuf Nabiha , Bej Asim K.
Published: July 2011

Background  In this study, we have investigated the chemotherapeutic potential of a purple violet pigment (PVP), which was isolated from a previously undescribed Antarctic Janthinobacterium sp. (Ant5‐2), against murine UV‐induced 2237 fibrosarcoma and B16F10 melanoma cells.

Methods  The 2237, B16F10, C50, and NIH3T3 cells were treated with PVP at different doses and for different times, and their proliferation and viability were detected by 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide (MTT) assay. Cell cycle arrest induced by PVP in 2237 fibrosarcoma cells was assessed by flow cytometry and expression analysis of cell cycle regulatory proteins were done by Western blot. Apoptosis induced by PVP in 2237 cells was observed by annexin‐V/propidium iodide double staining flow cytometry assay and fluorescence microscopy. To further determine the molecular mechanism of apoptosis induced by PVP, the changes in expression of Bcl‐2, Bax and cytochrome c were detected by Western blot. The loss of mitochondrial membrane potential in PVP treated 2237 cells was assessed by staining with JC‐1 dye following flow cytometry. Caspase‐3, Caspase‐9 and PARP cleavage were analyzed by Western blot and Caspase‐3 and ‐9 activities were measured by colorimetric assays.

Results  In vitro treatment of murine 2237 cells with the PVP resulted in decreased cell viability (13–79%) in a time (24–72 h) and dose (0.1–1 μm)‐dependent manner. The PVP‐induced growth inhibition in 2237 cells was associated with both G0/G1 and G2/M phase arrest accompanied with decrease in the expression of cyclin dependent kinases (Cdks) and simultaneous increase in the expression of cyclin dependent kinase inhibitors (Cdki) – Cip1/p21 and Kip1/p27. Further, we observed a significant increase in the apoptosis of the 2237 fibrosarcoma cells which was associated with an increased expression of pro‐apoptotic protein Bax, decreased expression of anti‐apoptotic proteins Bcl‐2, disruption of mitochondrial membrane potential, cytochrome c release, activation of caspase‐3, caspase‐9 and poly‐ADP‐ribose‐polymerase (PARP) cleavage.

Conclusions  We describe the anti‐cancer mechanism of the PVP for the first time from an Antarctic bacterium and suggest that the PVP could be used as a potent chemotherapeutic agent against nonmelanoma skin cancers.
Nonmelanoma skin cancer after renal transplantation: a single‐center experience in 1736 transplantations
Authors: Zavos George , Karidis Nikolaos P. , Tsourouflis Gerasimos , Bokos John , Diles Konstantinos , Sotirchos George , Theodoropoulou Eleni , Kostakis Alkiviadis
Published: July 2011

Background  Renal transplantation is associated with an increased incidence of nonmela‐noma skin cancer (NMSC) caused by immunosuppression. Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), the two major histological types of NMSC, exhibit more aggressive biological and clinical courses in renal transplant recipients (RTRs), with higher rates of recurrence and mortality than in the general population.

Methods  We retrospectively analyzed our experience of NMSC in 1736 renal transplantations performed over a 25‐year period. All cases of skin cancer after renal transplantation were included except those of skin cancer resulting from melanoma and mesenchymal skin tumors.

Results  In our series, the overall incidence of NMSC after transplantation was 2.2% (n = 39), and SCC represented the most frequent skin malignancy (64.1%), followed by BCC (17.9%), Bowen’s disease (10.2%), basosquamous carcinoma (5.1%), and a rare case of invasive sebaceous carcinoma (2.6%). A shift to newer immunosuppressive regimens after the initial diagnosis of NMSC had been implemented in eight cases (20.5%). The recurrence rate after initial treatment was 41% (n = 16), and distant metastatic disease was diagnosed in 15.4% (n = 6) of NMSC patients. The NMSC‐specific mortality rate was 25.6% (n = 10).

Conclusions  Nonmelanoma skin cancer remains a significant source of morbidity and mortality in RTRs, and post‐transplant surveillance should be increased.
Two novel germline KRAS mutations: expanding the molecular and clinical phenotype
Authors: Stark Z , Gillessen‐Kaesbach G , Ryan MM , Cirstea IC , Gremer L , Ahmadian MR , Savarirayan R , Zenker M
Published: July 2011

Stark Z, Gillessen‐Kaesbach G, Ryan MM, Cirstea IC, Gremer L, Ahmadian MR, Savarirayan R, Zenker M. Two novel germline KRAS mutations: expanding the molecular and clinical phenotype.

Noonan and Cardio‐facio‐cutaneous (CFC) syndromes are characterized by typical dysmorphic features, cardiac defects, short stature, variable ectodermal anomalies, and intellectual disability. Both belong to the Ras/mitogen‐activated protein kinase pathway group of disorders and clinical features overlap other related conditions, notably LEOPARD and Costello syndromes. KRAS mutations account for about 2% of reported Noonan and <5% of reported CFC cases. The mutation spectrum includes recurrent missense changes clustering in particular domains of the KRAS protein and conferring gain‐of‐function. We report three patients from two unrelated families with novel missense KRAS mutations, p.K147E and p.Y71H. Both mutations affect a residue which is highly conserved in KRAS and other RAS isoforms. One of the families includes a mother and son pair who represent the first report of a vertically transmitted KRAS mutation. In addition, the mother and son pair had peripheral neuropathy, complicated by Charcot arthropathy in the mother. An unusual phenotypic effect of the specific KRAS mutation or a coincidence of two independent disorders may be considered. KRAS mutation‐associated phenotypes appear to be subject to considerable clinical heterogeneity. All three cases highlight the challenges of clinical assessment in KRAS mutation‐positive patients, and the utility of molecular testing as an adjunct to diagnosis.
The use of recombinant human activated protein C (drotrecogin alpha) in solid organ transplant recipients: case series and review of the literature
Authors: Funk D.J. , Palma Vargas J. , Tuttle‐Newhall J. , Moretti E.W.
Published: July 2011

D.J. Funk, J. Palma Vargas, J. Tuttle‐Newhall, E.W. Moretti. The use of recombinant human activated protein C (drotrecogin alpha) in solid organ transplant recipients: case series and review of the literature. Transpl Infect Dis 2011: 13: 592–597. All rights reserved

Abstract: Septic shock occurs frequently in solid organ transplant (SOT) recipients. Standard therapy includes fluid resuscitation, the administration of antimicrobials, and source control of the infection. Adjunctive therapy with recombinant human activated protein C (rhaPC), also called drotrecogin alpha, is another treatment that is used in patients but has not been studied in SOT patients. Concerns regarding the use of this drug in this patient population include the risk of bleeding and the potential to adversely affect graft survival. Here we report the largest case series of SOT recipients with septic shock who received rhaPC. This was a retrospective chart review that looked at the impact of this drug in the SOT population. In this single‐center study, we identified 17 patients with a SOT and septic shock who received rhaPC. Six of the patients underwent kidney transplants, 5 received lung transplants, 4 received cadaveric liver transplants, and 2 received combined kidney/pancreas transplants. The average APACHE II score was 26.6 ± 5.5; all patients were undergoing mechanical ventilation and receiving vasopressors at the time of rhaPC administration. Overall mortality in the group was 23.5% (4/17) at 28 days post infusion. All of the deaths were due to complications of septic shock. Allograft survival was present in 13/17 (76.5%) of the patients at 28 days. Bleeding occurred in 17.6% of patients (3/17). The use of rhaPC appears to be associated with a favorable effect on mortality, with the potential for increased risk of bleeding. Clinicians must balance this risk with the potential benefit of this drug until further research can be conducted.
Antifungal susceptibility of Candida albicans in biofilms
Authors: Tobudic Selma , Kratzer Christina , Lassnigg Andrea , Presterl Elisabeth
Published: July 2011

Candida albicans are the most common fungi associated with biofilm‐related infections. Biofilms are defined as microbial communities encased in a matrix of extracellular polymeric substances. The most important feature of biofilm growth is the high resistance to antimicrobial agents that can be up to 1000‐fold greater than that of planktonic cells. This review discusses the factors affecting antifungal resistance as well as activity of mono‐ and combination therapy of different antifungal classes and antifungal activity in vitro and in vivo against C. albicans biofilms.
Early on‐treatment predictions of clinical outcomes using alpha‐fetoprotein and des‐gamma‐carboxy prothrombin responses in patients with advanced hepatocellular carcinoma
Authors: Lee Myoung Ha , Kim Seung Up , Kim Do Young , Ahn Sang Hoon , Choi Eun Hee , Lee Kwang Hun , Lee Do Yun , Seong Jinsil , Han Kwang‐Hyub , Chon Chae Yoon , Park Jun Yong
Published: July 2011

Background and Aim:  The clinical utility of alpha‐fetoprotein (AFP) and des‐γ‐carboxy prothrombin (DCP) as a predictor of treatment outcome in patients with advanced hepatocellular carcinoma (HCC) receiving hepatic artery infusional chemotherapy (HAIC) or concurrent chemoradiation therapy (CCRT) has been poorly defined.

Methods:  Between January 2003 and December 2007, we enrolled 127 treatment‐naïve patients who received HAIC (n = 60) or CCRT (n = 67) as an initial treatment modality. An AFP or DCP response was defined as a reduction of more than 20% from the baseline level.

Results:  AFP responders showed significantly better overall survival (OS) than non‐responders among patients with HAIC (median 17.3 vs 6.4 months, P < 0.001) and with CCRT (median 17.6 vs 8.7 months, P = 0.014). DCP responders in the CCRT group also showed significantly better progression‐free survival (PFS) than non‐responders (median 9.2 vs 3.1 months, P < 0.001). Multivariate Cox regression analyses showed that AFP response was independently predictive of OS in both groups (P = 0.009 in HAIC and P = 0.008 in CCRT) whereas DCP only predicted PFS in patients with CCRT (P = 0.015).

Conclusions:  Early on‐treatment AFP response was predictive of OS in treatment‐naïve patients with advanced HCC receiving HAIC and CCRT as an initial treatment modality. Furthermore, DCP response was useful for predicting PFS in patients with CCRT.
Hepatocellular carcinoma with duodenal invasion and metastasis
Authors: Liang Ja‐Der , Chen Chien‐Hung , Hsu Shih‐Jer , Sheu Jin‐Chuan , Yang Pei‐Ming , Lee Hsuan‐Shu , Lee Cha‐Ze , Huang Guan‐Tarn
Published: July 2011

Background and Aim:  Hepatocellular carcinoma (HCC) is the leading cause of cancer‐related deaths in Taiwan. HCC with duodenal involvement are rare and are associated with a poor prognosis. The purpose of this retrospective study was to collect clinical information and data regarding survival following various treatments.

Methods:  Between 1996 and 2009, 21 cases (17 men) were diagnosed with HCC and duodenal invasion and metastases by diagnostic imaging, endoscopy with biopsy, or surgically collected specimens sent to pathology. The clinical course was analyzed from the patients' medical records.

Results:  Gastrointestinal bleeding was reported in 18/21 patients. Diagnostic imaging showed that the majority of cases involved direct tumor invasion (predominantly from the right liver lobe) and six cases from metastasis. Tumor mass and ulcerations were the most common features noted on endoscopy. In addition to the component therapy and medication treatment, panendoscopic hemostasis, surgery, transcatheter arterial embolization, and radiotherapy were performed for the management of duodenal involvement and gastrointestinal bleeding. Survival duration after duodenal involvement ranged from 0.2 to 57.8 months (mean 10.5 months).

Conclusions:  Gastrointestinal bleeding in advanced HCC should raise suspicions of duodenal involvement. HCC can involve the duodenum by direct invasion (from either the left or right liver lobes) or metastasis. The prognosis for HCC patients with duodenal involvement is poor, but is improved by supportive care and application of various treatment modalities.
Laparoscopic splenectomy with interferon therapy in 100 hepatitis‐C‐virus‐cirrhotic patients with hypersplenism and thrombocytopenia
Authors: Akahoshi Tomohiko , Tomikawa Morimasa , Kawanaka Hirofumi , Furusyo Norihiro , Kinjo Nao , Tsutsumi Norifumi , Nagao Yoshihiro , Hayashi Jun , Hashizume Makoto , Maehara Yoshihiko
Published: July 2011

Background and Aim:  We intended to determine whether laparoscopic splenectomy (Lap‐Sp) contributes to treatment with interferon therapy in hepatitis C virus (HCV)‐cirrhotic patients with thrombocytopenia caused by hypersplenism.

Methods:  From December 2004 to August 2008, 100 cirrhotic patients (54 men and 46 women) underwent Lap‐Sp for a clinical application of interferon therapy. All the patients were Child–Pugh class A or B with thrombocytopenia (average platelet count, 56 × 103/mm3). The HCV genotype was type 1 in 80 patients and type 2 in 20 patients.

Results:  Pure laparoscopic or hand‐assisted laparoscopy was performed in 78 and 22 patients, respectively, without mortality. Conversion to open surgery was not required in any of the patients. The platelet counts improved (mean platelet count 172 × 103/mm3 1 month after surgery) and interferon (IFN) therapy was started in 97 patients. In this study period, 36 patients obtained a sustained virologic response. Eight patients discontinued IFN therapy because of depression, neutropenia or other reasons.

Conclusions:  Lap‐Sp permits most patients with HCV cirrhosis and hypersplenism to receive sufficient IFN therapy. Therefore, Lap‐Sp can become a strong supportive surgery for cirrhotic patients who require antiviral therapy.
DA6034 promotes gastric epithelial cell migration and wound‐healing through the mTOR pathway
Authors: Kim Young Woo , Lee Woo Hyung , Choi Seul Min , Seo Yoon Young , Ahn Byoung Ok , Kim Soon Hoe , Kim Sang Geon
Published: July 2011

Background and Aim: 7‐Carboxymethyloxy‐3′,4′,5‐trimethoxy flavone (DA6034), a synthetic derivative of eupatilin, has a protective effect on gastric mucosa against various ulcerogens, and is currently in the phase III clinical trial in the treatment of peptic ulcer disease. Cell migration and/or growth plays a role in the repair process of gastric ulcer, so this study investigated the effect of DA6034 on the movement and proliferation of gastric epithelial cells and its associated signaling pathway.

Methods: The migration of AGS or SNU484 human gastric epithelial cells was shown by scratch‐induced wound healing and transwell assays, and the proliferation of the cells was assessed by FACS and proliferation assays.

Results: Treatment of DA6034 promoted the migration of gastric epithelial cells in a concentration‐dependent manner. DA6034 treatment facilitated the phosphorylation of mTOR that led to an increase in the activity of S6K1, indicating its ability to activate mTOR and S6K1. Rapamycin aborted the wound‐healing effect of DA6034, which supported the role of mTOR activation in the wound‐healing process. In addition, DA6034 treatment increased PI3K‐dependent Akt phosphorylation, which was necessary for the enhancement of cell migration. DA6034, however, did not stimulate the proliferation of gastric epithelial cells, being consistent with no activation of ERK1/2 by the agent.

Conclusions: DA6034 has the ability to heal scratch wounds, which may result from an increase in gastric epithelial cell migration as mediated by PI3K‐Akt‐dependent activation of mTOR and S6K1. Our finding may be of help in understanding the molecular basis of the anti‐ulcer effect of DA6034.
Resistance of Helicobacter pylori strains to antibiotics in Korea with a focus on fluoroquinolone resistance
Authors: Chung Jun‐Won , Lee Gin Hyug , Jeong Jin‐Yong , Lee Sun Mi , Jung Ji Hoon , Choi Kee Don , Song Ho June , Jung Hwoon‐Yong , Kim Jin‐Ho
Published: July 2011

Background and Aim:  New regimens, including those with new fluoroquinolones, have been developed to overcome the antibiotic resistance of Helicobacter pylori. We aimed to assess the antibiotic resistance rates, as well as the molecular mechanisms of fluoroquinolone resistance, of the clinical isolates obtained in Korea.

Methods:  The minimal inhibitory concentration (MIC) values of ciprofloxacin, amoxicillin, clarithromycin, metronidazole and tetracycline were determined by the agar dilution method for 185 treatment‐naïve Helicobacter pylori isolates. The resistant strains were evaluated for the presence of point mutations in the quinolone resistance‐determining region (QRDR) of the gyrA and gyrB genes by direct nucleotide sequencing.

Results:  Twenty‐nine (29/185, 15.7%) of the strains were found to be resistant to ciprofloxacin. The resistance rates to amoxicillin, clarithromycin, metronidazole and tetracycline were 2.2% (four of 185), 10.8% (20 of 185), 30.3% (56 of 185) and 0.5% (one of 185), respectively. The most common mutations in the H. pylori gyrA gene were found at codons corresponding to Asp87 (16/29, 55.2%) and Asn91 (10/29, 34.5%).

Conclusions:  Primary H. pylori resistance to ciprofloxacin occurred at a high frequency. The fluoroquinolone resistance is most likely mediated through amino acid point mutation in the gyrA gene at Asn87 and Asp91.
Increasing the duration of dual amoxicillin plus omeprazole Helicobacter pylori eradication to 6 weeks: A pilot study
Authors: Attumi Taraq A , Graham David Y
Published: July 2011

Background and Aim:  Helicobacter pylori infections have become increasingly difficult to treat as antimicrobial resistance has increased. The aim of this study was to test the hypothesis that a 6‐week dual regimen of amoxicillin 1 gm and omeprazole 20 gm therapy b.i.d. would cure at least 90% of treatment‐naïve H. pylori infections.

Methods:  This was an open‐label prospective pilot study in which treatment‐naïve subjects with active H. pylori infection (positive by two tests) received dual amoxicillin 1 g and omeprazole 20 mg, b.i.d. daily for 6 weeks. Success was accessed by urea breath test 4–6 weeks later. A tentatively effective therapy was defined as a per‐protocol treatment success of 90% or greater; treatment success of 80% or less was prespecified as unacceptable.

Results:  Sixteen patients were included in the study (14 men, two women) with an average age of 49 years. At 16 patients, the prespecified stopping rule of six treatment failures was achieved (i.e. the 95% confidence interval excluded achieving the required 90% success rate even if 50 patients were entered). As per protocol, enrollment was stopped. Per‐protocol and intention‐to‐treat treatment success were both 62.5% (95% confidence interval, 35–84%). Compliance was greater than 99%. Five patients (31%) reported side‐effects, all of which were mild and none interrupted therapy.

Conclusion:  Despite the theory and pre‐existing data from Japan, in the USA, prolonging the duration of dual amoxicillin‐PPI therapy did not improve treatment outcome in 90% or more of our patients.
Understanding the recruitment and retention of overseas nurses: realist case study research in National Health Service Hospitals in the UK
Authors: O’Brien Terri , Ackroyd Stephen
Published: July 2011

O’BRIEN T and ACKROYD S. Nursing Inquiry 2012; 19: 39–50 Understanding the recruitment and retention of overseas nurses: realist case study research in National Health Service Hospitals in the UK

This paper illustrates one of the possible applications of critical realist ideas to the analysis of health services, in the use of comparative case study research design, to elucidate the causal social processes underlying events. In the research reported here, a comparative research design was used as a basis for improving our understanding of the processes involved in the assimilation of overseas nurses (OSN) into the salient long‐term workforce of the National Health Service (NHS) hospitals in the UK. The work brought to light the salient experiences of overseas nurses during their initial work in the NHS hospitals, and these were used as a basis for developing an account of the general mechanisms typically underlying the recruitment and assimilation at work. The authors conclude that successful assimilation is often hindered by the presence of occupational closure mechanisms, by which home nurses effectively excluded recruits from participation and promotion; these mechanisms, which articulate with everyday racism, threaten successful assimilation for obvious reasons. If the treatment recruits receive does not lead to withdrawal, it is because they typically have very strong economic motives to continue despite unfavourable and sometimes inhumane treatment. Thus, the research offered substantial reasons why recruitment policies should be reviewed by policy‐makers.
Understanding health decisions using critical realism: home‐dialysis decision‐making during chronic kidney disease
Authors: Harwood Lori , Clark Alexander M
Published: July 2011

HARWOOD L and CLARK AM. Nursing Inquiry 2012; 19: 29–38 Understanding health decisions using critical realism: home‐dialysis decision‐making during chronic kidney disease

This paper examines home‐dialysis decision making in people with Chronic Kidney Disease (CKD) from the perspective of critical realism. CKD programmes focus on patient education for self‐management to delay the progression of kidney disease and the preparation and support for renal replacement therapy e.g.) dialysis and transplantation. Home‐dialysis has clear health, societal and economic benefits yet service usage is low despite efforts to realign resources and educate individuals. Current research on the determinants of modality selection is superficial and insufficient to capture the complexities embedded in the process of dialysis modality selection. Predictors of home‐dialysis selection and the effect of chronic kidney disease educational programmes provide a limited explanation of this experience. A re‐conceptualization of the problem is required in order to fully understand this process. The epistemology and ontology of critical realism guides our knowledge and methodology particularly suited for examination of these complexities. This approach examines the deeper mechanisms and wider determinants associated with modality decision making, specifically who chooses home dialysis and under what circumstances. Until more is known regarding dialysis modality decision making service usage of home dialysis will remain low as interventions will be based on inadequate epistemology.
Association between the expression pattern of p16, pRb and p53 and the response to intravesical bacillus Calmette–Guerin therapy in patients with urothelial carcinoma in situ of the urinary bladder
Authors: Sato Masakazu , Yanai Hiroyuki , Morito Toshiaki , Oda Wakako , Shin‐no Yoko , Yamadori Ichiro , Tshushima Tomoyasu , Yoshino Tadashi
Published: July 2011

There is limited data regarding the association between the expression of cell cycle‐regulating molecules and the response of patients with urothelial carcinoma in situ (CIS) to bacillus Calmette–Guerin (BCG) therapy. To examine the relationship between p16, pRb and p53 expression in bladder CIS and patient response to initial BCG therapy, we performed immunohistochemical studies for 27 patients with bladder CIS. Overexpression of p16, pRb, and p53 was observed in 37%, 41%, and 48% of patients, respectively. Initial BCG therapy was effective in 21 patients (78%). Coexistence of papillary urothelial carcinoma, depth (pTa or pT1) and grade of coexisting papillary carcinoma did not affect the response to BCG therapy. pRb overexpression had a significant relationship to poor response to BCG therapy (P= 0.027). The results of this study indicate that overexpression of pRb in bladder CIS predicts poor response of intravesical BCG instillation and status of p16 and p53 may not be predictive of initial BCG failure.
Prevalence of potentially reversible conditions in dementia and mild cognitive impairment in a geriatric clinic
Authors: Muangpaisan Weerasak , Petcharat Chonachan , Srinonprasert Varalak
Published: July 2011

Aim:  To examine the prevalence of potentially reversible conditions in dementia and mild cognitive impairment (MCI) patients in a geriatric clinic.

Methods:  We retrospectively reviewed the medical records of patients who attended the outpatient geriatric clinic at Siriraj Hospital, Bangkok between January 2005 and December 2010. We collected the data regarding potentially reversible conditions of cognitive impairment.

Results:  There were 233 patients newly diagnosed with dementia and 60 patients diagnosed with MCI. We found potentially reversible causes of dementia in 17 patients (7.3%). The causes were hypothyroidism (2.6%), B12 deficiency (1.7%), normal pressure hydrocephalus (NPH) (0.9%), depression (0.9%), folate deficiency (0.4%), reactive Venereal Disease Research Laboratory (VDRL; 0.4%) and chronic subdural hematoma (CSH; 0.4%). The patients with NPH and CSH were clinically suspicious for having such conditions before the investigations, while patients with low B12 level, low folate level, hypothyroidism and VDRL+ were not. In the MCI group, we found potentially reversible causes in two patients (3.3%), these were B12 deficiency (1.7%) and hypothyroidism (1.7%). Clinical improvement after treatment of the potentially reversible conditions was seen in four patients (one NPH, one subdural hematoma and two with depression) in dementia group (1.7%) and none in the MCI group. All were partially reversed.

Conclusion:  Routine investigations might be more warranted for metabolic conditions (B12 level and hypothyroidism) as clinical presentations are not suggestive of the conditions. However, reversibility of dementia might not occur in these cases. Neuroimaging should be performed selectively as clinically indicated. Truly reversible conditions are rare and occur in surgical and depressive patients. Geriatr Gerontol Int 2012; 12: 59–64.
Role of the mTOR complex 1 pathway in the in vivo maintenance of the intestinal mucosa by oral intake of amino acids
Authors: Nakamura Akira , Hara Kenta , Yamamoto Kazuhiro , Yasuda Hisafumi , Moriyama Hiroaki , Hirai Midori , Nagata Masao , Yokono Koichi
Published: July 2011

Aim:  Oral intake of nutrients is often compromised in elderly, multimorbid patients, but parenteral nutrition causes intestinal atrophy and impairs intestinal function. To uncover the molecular mechanisms by which amino acids are involved in intestinal atrophy and recovery, we studied whether the rapamycin‐sensitive mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) pathway is involved in this process.

Methods:  C57BL/6N mice were fed a glucose solution alone, glucose solution with amino acids or normal chow diet for various lengths of time. Intestinal sections were prepared from these mice and the villus height and villus density were quantified. As a readout for the mTORC1 pathway, the phosphorylation of the ribosomal S6 protein (S6) was analyzed by immunostaining and immunoblotting. To confirm the role of the mTORC1 pathway, the inhibitory effect of a specific mTOR inhibitor, rapamycin, was examined.

Results:  Inducing fasting in mice fed only glucose caused time‐dependent intestinal mucosal atrophy, whereas supplementation with amino acids protected the intestinal mucosa from atrophy. Phosphorylation of S6 decreased in the intestinal mucosa of mice fed only glucose, whereas supplementation with amino acids increased S6 phosphorylation. Importantly, intraperitoneal injection of rapamycin attenuated the protective effect of amino acids on the intestinal mucosa in a pattern consistent with the decrease of S6 phosphorylation.

Conclusions:  These results indicate that the mTORC1 pathway plays a crucial role in the in vivo maintenance of the intestinal mucosa by the oral intake of amino acids. Geriatr Gerontol Int 2012; 12: 131–139.