bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the mineralogical effects of an experimental forest fire on a goethite/ferrihydrite soil with a topsoil that contains hematite, maghemite and goethite
Authors: Nørnberg P. , Vendelboe A. L. , Gunnlaugsson H. P. , Merrison J. P. , Finster K. , Jensen S. K 
Published: August 2009

AbstractA long-standing unresolved puzzle related to the Danish temperate humid climate is the presence of extended areas with large Fe contents, where goethite and ferrihydrite are present in the topsoil along with hematite and maghemite. Hematite and, particularly, maghemite would normally be interpreted as the result of high temperature as found after forest fires. However, a body of evidence argues against these sites having been exposed to fire. In an attempt to get closer to an explanation of this Fe mineralogy, an experimental forest fire was produced. The results showed a clear mineralogical zonation down to 10 cm depth. This was not observed at the natural sites, which contained a mixture of goethite/ferrihydrite, hematite and maghemite down to 20 cm depth. The experimental forest fire left charcoal and ashes at the topsoil, produced high pH and decreased organic matter content, all of which is in contrast to the natural sites. The conclusion from this work is that the mineralogy of these sites is not consistent with exposure to forest fire, but may instead result from long-term transformation in a reducing environment, possibly involving microbiology.
Enhancement of vascular progenitor potential by protein kinase A through dual induction of Flk-1 and Neuropilin-1
Authors: Yamamizu Kohei , Kawasaki Kyoko , Katayama Shiori , Watabe Tetsuro , Yamashita Jun K. 
Published: August 2009

AbstractFine tuning of vascular endothelial growth factor (VEGF) signaling is critical in endothelial cell (EC) differentiation and vascular development. Nevertheless, the system for regulating the sensitivity of VEGF signaling has remained unclear. Previously, we established an embryonic stem cell culture reproducing early vascular development using Flk1 (VEGF receptor-2)+ cells as common progenitors, and demonstrated that cyclic adenosine monophosphate (cAMP) enhanced VEGF-induced EC differentiation. Here we show that protein kinase A (PKA) regulates sensitivity of Flk1+ vascular progenitors to VEGF signaling for efficient EC differentiation. Blockade of PKA perturbed EC differentiation and vascular formation in vitro and ex vivo. Overexpression of constitutive active form of PKA (CA-PKA) potently induced EC differentiation and vascular formation. Expression of Flk1 and Neuropilin-1 (NRP1), which form a selective and sensitive receptor for VEGF165, was increased only in CA-PKA–expressing progenitors, enhancing the sensitivity of the progenitors to VEGF165 by more than 10 times. PKA activation induced the formation of a VEGF165, Flk1, and NRP1 protein complex in vascular progenitors. These data indicate that PKA regulates differentiation potential of vascular progenitors to be endothelial competent via the dual induction of Flk1 and NRP1. This new-mode mechanism regulating “progenitor sensitivity” would provide a novel understanding in vascular development and regeneration.
The role of the human cytomegalovirus UL111A gene in down-regulating CD4+ T-cell recognition of latently infected cells: implications for virus elimination during latency
Authors: Cheung Allen K. L. , Gottlieb David J. , Plachter Bodo , Pepperl-Klindworth Sandra , Avdic Selmir , Cunningham Anthony L. , Abendroth Allison , Slobedman Barry 
Published: August 2009

AbstractThe capacity of human cytomegalovirus (HCMV) to establish and maintain a latent infection from which it can later reactivate ensures its widespread distribution in the population, but the mechanisms enabling maintenance of latency in the face of a robust immune system are poorly understood. We examined the role of the HCMV UL111A gene, which encodes homologs of the immunosuppressive cytokine interleukin-10 in the context of latent infection of myeloid progenitor cells. A UL111A deletion virus was able to establish, maintain, and reactivate from experimental latency in a manner comparable with parental virus, but major histocompatibility complex class II levels increased significantly on the surfaces of cells infected with the deletion virus. Importantly, there was an increase in both allogeneic and autologous peripheral blood mononuclear cells and CD4+ T-cell responses to UL111A deletion virus-infected myeloid progenitors, indicating that loss of the capacity to express viral interleukin-10 during latency results in latently infected cells becoming more readily recognizable by a critical arm of the immune response. The detection of a viral gene that suppresses CD4+ T-cell recognition of latently infected cells identifies an immune evasion strategy that probably enhances the capacity of HCMV to persist in a latent state within the human host.
Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts
Authors: Le Dieu Rifca , Taussig David C. , Ramsay Alan G. , Mitter Richard , Miraki-Moud Faridah , Fatah Rewas , Lee Abigail M. , Lister T. Andrew , Gribben John G. 
Published: August 2009

Abstract
Understanding how the immune system in patients with cancer interacts with malignant cells is critical for the development of successful immunotherapeutic strategies. We studied peripheral blood from newly diagnosed patients with acute myeloid leukemia (AML) to assess the impact of this disease on the patients' T cells. The absolute number of peripheral blood T cells is increased in AML compared with healthy controls. An increase in the absolute number of CD3+56+ cells was also noted. Gene expression profiling on T cells from AML patients compared with healthy donors demonstrated global differences in transcription suggesting aberrant T-cell activation patterns. These gene expression changes differ from those observed in chronic lymphocytic leukemia (CLL), indicating the heterogeneous means by which different tumors evade the host immune response. However, in common with CLL, differentially regulated genes involved in actin cytoskeletal formation were identified, and therefore the ability of T cells from AML patients to form immunologic synapses was assessed. Although AML T cells could form conjugates with autologous blasts, their ability to form immune synapses and recruit phosphotyrosine signaling molecules to the synapse was significantly impaired. These findings identify T-cell dysfunction in AML that may contribute to the failure of a host immune response against leukemic blasts.
Bone marrow stem and progenitor cell contribution to neovasculogenesis is dependent on model system with SDF-1 as a permissive trigger
Authors: Madlambayan Gerard J. , Butler Jason M. , Hosaka Koji , Jorgensen Marda , Fu Dongtao , Guthrie Steven M. , Shenoy Anitha K. , Brank Adam , Russell Kathryn J. , Otero Jaclyn , Siemann Dietmar W. , Scott Edward W. , Cogle Christopher R. 
Published: August 2009

Abstract
Adult bone marrow (BM) contributes to neovascularization in some but not all settings, and reasons for these discordant results have remained unexplored. We conducted novel comparative studies in which multiple neovascularization models were established in single mice to reduce variations in experimental methodology. In different combinations, BM contribution was detected in ischemic retinas and, to a lesser extent, Lewis lung carcinoma cells, whereas B16 melanomas showed little to no BM contribution. Using this spectrum of BM contribution, we demonstrate the necessity for site-specific expression of stromal-derived factor-1α (SDF-1α) and its mobilizing effects on BM. Blocking SDF-1α activity with neutralizing antibodies abrogated BM-derived neovascularization in lung cancer and retinopathy. Furthermore, secondary transplantation of single hematopoietic stem cells (HSCs) showed that HSCs are a long-term source of neovasculogenesis and that CD133+CXCR4+ myeloid progenitor cells directly participate in new blood vessel formation in response to SDF-1α. The varied BM contribution seen in different model systems is suggestive of redundant mechanisms governing postnatal neovasculogenesis and provides an explanation for contradictory results observed in the field.
A randomized, controlled clinical trial of ketoprofen for sickle-cell disease vaso-occlusive crises in adults
Authors: Bartolucci Pablo , El Murr Tony , Roudot-Thoraval Françoise , Habibi Anoosha , Santin Aline , Renaud Bertrand , Noël Violaine , Michel Marc , Bachir Dora , Galactéros Frédéric , Godeau Bertrand 
Published: August 2009

Abstract
Vaso-occlusive crisis (VOC) is the primary cause of hospitalization of patients with sickle-cell disease. Treatment mainly consists of intravenous morphine, which has many dose-related side effects. Nonsteroidal antiinflammatory drugs have been proposed to provide pain relief and decrease the need for opioids. Nevertheless, only a few underpowered trials of nonsteroidal antiinflammatory drugs for sickle-cell VOC have been conducted, and conflicting results were reported. We conducted a phase 3, double-blind, randomized, placebo-controlled trial with ketoprofen (300 mg/day for 5 days), a nonselective cyclooxygenase inhibitor, for severe VOC in adults. A total of 66 VOC episodes were included. The primary efficacy outcome was VOC duration. The secondary end points were morphine consumption, pain relief, and treatment failure. Seven VOC episodes in each group were excluded from the analysis because of treatment failures. No significant between-group differences were observed for the primary outcome or the secondary end points. Thus, although ketoprofen was well-tolerated, it had no significant efficacy as treatment of VOC requiring hospitalization. These findings argue against its systematic use in this setting.
Stage-specific susceptibility of human erythroblasts to Plasmodium falciparum malaria infection
Authors: Tamez Pamela A. , Liu Hui , Fernandez-Pol Sebastian , Haldar Kasturi , Wickrema Amittha 
Published: August 2009

Abstract
Malaria parasites are known to invade and develop in erythrocytes and reticulocytes, but little is known about their infection of nucleated erythroid precursors. We used an in vitro cell system that progressed through basophilic, polychromatic, orthochromatic, and reticulocyte stages to mature erythrocytes. We show that orthochromatic cells are the earliest stages that may be invaded by Plasmodium falciparum, the causative agent of fatal human malaria. Susceptibility to invasion is distinct from intracellular survival and occurs at a time of extensive erythroid remodeling. Together these data suggest that the potential for complexity of host interactions involved in infection may be vastly greater than hitherto realized.
Automated threshold detection for auditory brainstem responses: comparison with visual estimation in a stem cell transplantation study
Authors: Bogaerts Sofie , Clements John D , Sullivan Jeremy M , Oleskevich Sharon 
Published: August 2009

Abstract

Background
Auditory brainstem responses (ABRs) are used to study auditory acuity in animal-based medical research. ABRs are evoked by acoustic stimuli, and consist of an electrical signal resulting from summated activity in the auditory nerve and brainstem nuclei. ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Traditionally, threshold has been assessed by visual estimation of a series of ABRs evoked by different sound intensities. Here we develop an automated threshold detection method that eliminates the variability and subjectivity associated with visual estimation.

Results
The automated method is a robust computational procedure that detects the sound level at which the peak amplitude of the evoked ABR signal first exceeds four times the standard deviation of the baseline noise. Implementation of the procedure was achieved by evoking ABRs in response to click and tone stimuli, under normal and experimental conditions (adult stem cell transplantation into cochlea). Automated detection revealed that the threshold shift from pre- to post-surgery hearing levels was similar in mice receiving stem cell transplantation or sham injection for click and tone stimuli. Visual estimation by independent observers corroborated these results but revealed variability in ABR threshold shifts and significance levels for stem cell-transplanted and sham-injected animals.

Conclusion
In summary, the automated detection method avoids the subjectivity of visual analysis and offers a rapid, easily accessible http://axograph.com/source/abr.html approach to measure hearing threshold levels in auditory brainstem response.
Psychotropic drugs up-regulate the expression of cholesterol transport proteins including ApoE in cultured human CNS- and liver cells
Authors: Vik-Mo Audun O , Fernø Johan , Skrede Silje , Steen Vidar M 
Published: August 2009

Abstract

Background
Disturbances in lipid homeostasis and myelination have been proposed in the pathophysiology of schizophrenia and bipolar disorder. We have previously shown that several antipsychotic and antidepressant drugs increase lipid biosynthesis through activation of the Sterol Regulatory Element-Binding Protein (SREBP) transcription factors, which control the expression of numerous genes involved in fatty acid and cholesterol biosynthesis. The aim of the present proof-of-principle study was to investigate whether such drugs also affect lipid transport and export pathways in cultured human CNS and liver cells.

Results
Quantitative PCR and immunoblotting were used to determine the level of lipid transport genes in human glioblastoma (GaMg) exposed to clozapine, olanzapine, haloperidol or imipramine. The effect of some of these drugs was also investigated in human astrocytoma (CCF-STTG1), neuroblastoma (SH-SY5Y) and hepatocellular carcinoma (HepG2) cells. We found significant transcriptional changes of cholesterol transport genes (ApoE, ABCA1, NPC1, NPC2, NPC1L1), which are predominantly controlled by the Liver X receptor (LXR) transcription factor. The up-regulation was observed after 24 to 48 hours of drug exposure, which is markedly delayed as compared to the drug-induced SREBP-controlled stimulation of lipid biosynthesis seen after 6 hours.

Conclusion
Our data show that stimulation of cellular lipid biosynthesis by amphiphilic psychotropic drugs is followed by a transcriptional activation of cholesterol transport and efflux pathways. Such effects may be relevant for both therapeutic effects and metabolic adverse effects of psychotropic drugs.
Attitudes, norms and controls influencing lifestyle risk factor management in general practice
Authors: Ampt Amanda J , Amoroso Cheryl , Harris Mark F , McKenzie Suzanne H , Rose Vanessa K , Taggart Jane R 
Published: August 2009

Abstract

Background
With increasing rates of chronic disease associated with lifestyle behavioural risk factors, there is urgent need for intervention strategies in primary health care. Currently there is a gap in the knowledge of factors that influence the delivery of preventive strategies by General Practitioners (GPs) around interventions for smoking, nutrition, alcohol consumption and physical activity (SNAP). This qualitative study explores the delivery of lifestyle behavioural risk factor screening and management by GPs within a 45–49 year old health check consultation. The aims of this research are to identify the influences affecting GPs' choosing to screen and choosing to manage SNAP lifestyle risk factors, as well as identify influences on screening and management when multiple SNAP factors exist.

Methods
A total of 29 audio-taped interviews were conducted with 15 GPs and one practice nurse over two stages. Transcripts from the interviews were thematically analysed, and a model of influencing factors on preventive care behaviour was developed using the Theory of Planned Behaviour as a structural framework.

Results
GPs felt that assessing smoking status was straightforward, however some found assessing alcohol intake only possible during a formal health check. Diet and physical activity were often inferred from appearance, only being assessed if the patient was overweight. The frequency and thoroughness of assessment were influenced by the GPs' personal interests and perceived congruence with their role, the level of risk to the patient, the capacity of the practice and availability of time. All GPs considered advising and educating patients part of their professional responsibility. However their attempts to motivate patients were influenced by perceptions of their own effectiveness, with smoking causing the most frustration. Active follow-up and referral of patients appeared to depend on the GPs' orientation to preventive care, the patient's motivation, and cost and accessibility of services to patients.

Conclusion
General practitioner attitudes, normative influences from both patients and the profession, and perceived external control factors (time, cost, availability and practice capacity) all influence management of behavioural risk factors. Provider education, community awareness raising, support and capacity building may improve the uptake of lifestyle modification interventions.
Comparison of rapid tests for detection of rifampicin-resistant Mycobacterium tuberculosis in Kampala, Uganda
Authors: Ogwang Sam , Asiimwe Benon B , Traore Hamidou , Mumbowa Francis , Okwera Alphonse , Eisenach Kathleen D , Kayes Susan , Jones-López Edward C , McNerney Ruth , Worodria William , Ayakaka Irene , Mugerwa Roy D , Smith Peter G , Ellner Jerrold , Joloba Moses L 
Published: August 2009

Abstract

Background
Drug resistant tuberculosis (TB) is a growing concern worldwide. Rapid detection of resistance expedites appropriate intervention to control the disease. Several technologies have recently been reported to detect rifampicin resistant Mycobacterium tuberculosis directly in sputum samples. These include phenotypic culture based methods, tests for gene mutations and tests based on bacteriophage replication. The aim of the present study was to assess the feasibility of implementing technology for rapid detection of rifampicin resistance in a high disease burden setting in Africa.

Methods
Sputum specimens from re-treatment TB patients presenting to the Mulago Hospital National TB Treatment Centre in Kampala, Uganda, were examined by conventional methods and simultaneously used in one of the four direct susceptibility tests, namely direct BACTEC 460, Etest, "in-house" phage test, and INNO- Rif.TB. The reference method was the BACTEC 460 indirect culture drug susceptibility testing. Test performance, cost and turn around times were assessed.

Results
In comparison with indirect BACTEC 460, the respective sensitivities and specificities for detecting rifampicin resistance were 100% and 100% for direct BACTEC and the Etest, 94% and 95% for the phage test, and 87% and 87% for the Inno-LiPA assay. Turn around times ranged from an average of 3 days for the INNO-LiPA and phage tests, 8 days for the direct BACTEC 460 and 20 days for the Etest. All methods were faster than the indirect BACTEC 460 which had a mean turn around time of 24 days. The cost per test, including labour ranged from $18.60 to $41.92 (USD).

Conclusion
All four rapid technologies were shown capable of detecting rifampicin resistance directly from sputum. The LiPA proved rapid, but was the most expensive. It was noted, however, that the LiPA test allows sterilization of samples prior to testing thereby reducing the risk of accidental laboratory transmission. In contrast the Etest was low cost, but slow and would be of limited assistance when treating patients. The phage test was the least reproducible test studied with failure rate of 27%. The test preferred by the laboratory personnel, direct BACTEC 460, requires further study to determine its accuracy in real-time treatment decisions in Uganda.
Five-year follow-up of children with perinatal HIV-1 infection receiving early highly active antiretroviral therapy
Authors: Chiappini Elena , Galli Luisa , Tovo Pier-Angelo , Gabiano Clara , Lisi Catiuscia , Bernardi Stefania , Viganò Alessandra , Guarino Alfredo , Giaquinto Carlo , Esposito Susanna , Badolato Raffaele , Di Bari Cesare , Rosso Raffaella , Genovese Orazio , Masi Massimo , Mazza Antonio , de Martino Maurizio 
Published: August 2009

Abstract

Background
Early highly active antiretroviral therapy (HAART), started within the first months of age, has been proven to be the optimal strategy to prevent immunological and clinical deterioration in perinatally HIV-infected children. Nevertheless, data about long-term follow-up of early treated children are lacking.

Methods
We report data from 40 perinatally HIV-infected-children receiving early HAART, with a median follow-up period of 5.96 years (interquartile range [IQR]:4.21–7.62). Children were enrolled at birth in the Italian Register for HIV Infection in Children. Comparison with 91 infected children born in the same period, followed-up from birth, and receiving deferred treatment was also provided.

Results
Nineteen children (47.5%) were still receiving their first HAART regimen at last follow-up. In the remaining children the first regimen was discontinued, after a median period of 3.77 years (IQR: 1.71–5.71) because of viral failure (8 cases), liver toxicity (1 case), structured therapy interruption (3 cases), or simplification/switch to a PI-sparing regimen (9 cases). Thirty-nine (97.5%) children showed CD4+ T-lymphocyte values>25%, and undetectable viral load was reached in 31 (77.5%) children at last visit. Early treated children displayed significantly lower viral load than not-early treated children, until 6 years of age, and higher median CD4+ T-lymphocyte percentages until 4 years of age. Twenty-seven (29.7%) not-early treated vs. 0/40 early treated children were in clinical category C at last follow-up (P < 0.0001).

Conclusion
Our findings suggest that clinical, virologic and immunological advantages from early-HAART are long-lasting. Recommendations indicating the long-term management of early treated children are needed.