bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of human papillomavirus infection in women undergoing routine cervical cancer screening in Spain: the CLEOPATRE study
Authors: Roura Esther , Iftner Thomas , Vidart José Antonio , Kjaer Susanne Krüger , Bosch F Xavier , Muñoz Nubia , Palacios Santiago , Rodriguez Maria San Martin , Morillo Carmen , Serradell Laurence , Torcel-Pagnon Laurence , Cortes Javier , Castellsagué Xavier ,   the CLEOPATRE Spain Study Group
Published: June 2012

Background

Human papillomavirus (HPV) is a sexually transmitted infection that may lead to development of precancerous and cancerous lesions of the cervix. The aim of the current study was to investigate socio-demographic, lifestyle, and medical factors for potential associations with cervical HPV infection in women undergoing cervical cancer screening in Spain.

Methods

The CLEOPATRE Spain study enrolled 3 261 women aged 18–65 years attending cervical cancer screening across the 17 Autonomous Communities. Liquid-based cervical samples underwent cytological examination and HPV testing. HPV positivity was determined using the Hybrid Capture II assay, and HPV genotyping was conducted using the INNO-LiPA HPV Genotyping Extra assay. Multivariate logistic regression was used to identify putative risk factors for HPV infection.

Results

A lifetime number of two or more sexual partners, young age (18–25 years), a history of genital warts, and unmarried status were the strongest independent risk factors for HPV infection of any type. Living in an urban community, country of birth other than Spain, low level of education, and current smoking status were also independent risk factors for HPV infection. A weak inverse association between condom use and HPV infection was observed. Unlike monogamous women, women with two or more lifetime sexual partners showed a lower risk of infection if their current partner was circumcised (P for interaction, 0.005) and a higher risk of infection if they were current smokers (P for interaction, 0.01).

Conclusion

This is the first large-scale, country-wide study exploring risk factors for cervical HPV infection in Spain. The data strongly indicate that variables related to sexual behavior are the main risk factors for HPV infection. In addition, in non-monogamous women, circumcision of the partner is associated with a reduced risk and smoking with an increased risk of HPV infection.
Steroid receptor coactivators, HER-2 and HER-3 expression is stimulated by tamoxifen treatment in DMBA-induced breast cancer
Authors: Moi Line L Haugan , Flågeng Marianne Hauglid , Gjerde Jennifer , Madsen Andre , Røst Therese Halvorsen , Gudbrandsen Oddrun Anita , Lien Ernst A , Mellgren Gunnar
Published: June 2012

Background

Steroid receptor coactivators (SRCs) may modulate estrogen receptor (ER) activity and the response to endocrine treatment in breast cancer, in part through interaction with growth factor receptor signaling pathways. In the present study the effects of tamoxifen treatment on the expression of SRCs and human epidermal growth factor receptors (HERs) were examined in an animal model of ER positive breast cancer.

Methods

Sprague-Dawley rats with DMBA-induced breast cancer were randomized to 14 days of oral tamoxifen 40 mg/kg bodyweight/day or vehicle only (controls). Tumors were measured throughout the study period. Blood samples and tumor tissue were collected at sacrifice and tamoxifen and its main metabolites were quantified using LC-MS/MS. The gene expression in tumor of SRC-1, SRC-2/transcription intermediary factor-2 (TIF-2), SRC-3/amplified in breast cancer 1 (AIB1), ER, HER-1, -2, -3 and HER-4, as well as the transcription factor Ets-2, was measured by real-time RT-PCR. Protein levels were further assessed by Western blotting.

Results

Tamoxifen and its main metabolites were detected at high concentrations in serum and accumulated in tumor tissue in up to tenfolds the concentration in serum. Mean tumor volume/rat decreased in the tamoxifen treated group, but continued to increase in controls. The mRNA expression levels of SRC-1 (P = 0.035), SRC-2/TIF-2 (P = 0.002), HER-2 (P = 0.035) and HER-3 (P = 0.006) were significantly higher in tamoxifen treated tumors compared to controls, and the results were confirmed at the protein level using Western blotting. SRC-3/AIB1 protein was also higher in tamoxifen treated tumors. SRC-1 and SRC-2/TIF-2 mRNA levels were positively correlated with each other and with HER-2 (P ≤ 0.001), and the HER-2 mRNA expression correlated with the levels of the other three HER family members (P < 0.05). Furthermore, SRC-3/AIB1 and HER-4 were positively correlated with each other and Ets-2 (P < 0.001).

Conclusions

The expression of SRCs and HER-2 and -3 is stimulated by tamoxifen treatment in DMBA-induced breast cancer. Stimulation and positive correlation of coactivators and HERs may represent an early response to endocrine treatment. The role of SRCs and HER-2 and -3 should be further studied in order to evaluate their effects on response to long-term tamoxifen treatment.
Colon cancer molecular subtypes identified by expression profiling and associatedto stroma, mucinous type and different clinical behavior
Authors: Perez Villamil Beatriz , Romera Lopez Alejandro , Hernandez Prieto Susana , Lopez Campos Guillermo , Calles Antonio , Lopez Asenjo Jose Antonio , Sanz Ortega Julian , Fernandez Perez Cristina , Sastre Javier , Alfonso Rosario , Caldes Trinidad , Martin Sanchez Fernando , Diaz Rubio Eduardo
Published: June 2012

Background

Colon cancer patients with the same stage show diverse clinical behavior dueto tumor heterogeneity. We aimed to discover distinct classes of tumorsbased on microarray expression patterns, to analyze whether the molecularclassification correlated with the histopathological stages or otherclinical parameters and to study differences in the survival.

Methods

Hierarchical clustering was performed for class discovery in 88 colon tumors(stages I to IV). Pathways analysis and correlations between clinicalparameters and our classification were analyzed. Tumor subtypes werevalidated using an external set of 78 patients. A 167 gene signatureassociated to the main subtype was generated using the 3-Nearest-Neighbormethod. Coincidences with other prognostic predictors were assesed.

Results

Hierarchical clustering identified four robust tumor subtypes withbiologically and clinically distinct behavior. Stromal components(p < 0.001), nuclear β-catenin (p = 0.021),mucinous histology (p = 0.001), microsatellite-instability(p = 0.039) and BRAF mutations (p < 0.001) wereassociated to this classification but it was independent of Dukes stages(p = 0.646). Molecular subtypes were established from stage I.High-stroma-subtype showed increased levels of genes and altered pathwaysdistinctive of tumour-associated-stroma and components of the extracellularmatrix in contrast to Low-stroma-subtype. Mucinous-subtype was reflected bythe increased expression of trefoil factors and mucins as well as by ahigher proportion of MSI andBRAFmutations. Tumor subtypes werevalidated using an external set of 78 patients. A 167 gene signatureassociated to the Low-stroma-subtype distinguished low risk patients fromhigh risk patients in the external cohort (Dukes B andC:HR = 8.56(2.53-29.01); Dukes B,C andD:HR = 1.87(1.07-3.25)). Eight different reported survival genesignatures segregated our tumors into two groups the Low-stroma-subtype andthe other tumor subtypes.

Conclusions

We have identified novel molecular subtypes in colon cancer with distinctbiological and clinical behavior that are established from the initiation ofthe tumor. Tumor microenvironment is important for the classification andfor the malignant power of the tumor. Differential gene sets and biologicalpathways characterize each tumor subtype reflecting underlying mechanisms ofcarcinogenesis that may be used for the selection of targeted therapeuticprocedures. This classification may contribute to an improvement in themanagement of the patients with CRC and to a more comprehensiveprognosis.
Horizontal equity and mental health care: a study of priority ratings by clinicians and teams at outpatient clinics
Authors: Holman Per Arne , Ruud Torleif , Grepperud Sverre
Published: June 2012

Background

In Norway, admission teams at Community Mental Health Centres (CMHCs) assess referrals from General Practitioners (GPs), and classify the referrals into priority groups according to treatment needs, as defined in the Act of Patient Rights. In this study, we analyzed classification of similar referrals to determine the reliability of classification into priority groups (i.e., horizontal equity).

Methods

Twenty anonymous case vignettes based on representative referrals were classified by 42 admission team members at 16 CMHCs in the South-East Health Region of Norway. All clinicians were experienced, and were responsible for priority setting at their centres. The classifications were first performed independently by the 42 clinicians (i.e., individual rating), and then evaluated utilizing team consensus within each CMHC (i.e., team rating). Interrater reliability was estimated using intraclass correlation coefficients (ICCs) while the reliability of rating across raters and units (generalizability) were estimated using generalizability analysis.

Results

The ICCs (2.1 single measure, absolute agreement) varied between 0.40 and 0.51 using individual ratings and between 0.39 and 0.58 using team ratings. Our findings suggest a fair (low) degree of interrater reliability, and no improvement of team ratings was observed when compared to individual ratings. The generalizability analysis, for one rater within each unit, yields a generalizability coefficient of 0.50 and a dependability coefficient of 0.53 (D study). These findings confirm that the reliability of ratings across raters and across units is low. Finally, the degree of inconsistency, for an average measurement, appears to be higher within units than between units (G study).

Conclusion

The low interrater reliability and generalizability found in our study suggests that horizontal equity to mental health services is not ensured with respect to priority. Priority -setting in teams provides no significant improvement compared to individual rating, and the additional use of these resources may be questionable. Improved guidelines, tutorials, training and calibration of clinicians may be utilized to improve the reliability of priority-setting.
Construction of microbial platform for an energy-requiring bioprocess: practical 2′-deoxyribonucleoside production involving a C−C coupling reaction with high energy substrates
Authors: Horinouchi Nobuyuki , Sakai Takafumi , Kawano Takako , Matsumoto Seiichiro , Sasaki Mie , Hibi Makoto , Shima Jun , Shimizu Sakayu , Ogawa Jun
Published: June 2012

Background

Reproduction and sustainability are important for future society, and bioprocesses are one technology that can be used to realize these concepts. However, there is still limited variation in bioprocesses and there are several challenges, especially in the operation of energy-requiring bioprocesses. As an example of a microbial platform for an energy-requiring bioprocess, we established a process that efficiently and enzymatically synthesizes 2′-deoxyribonucleoside from glucose, acetaldehyde, and a nucleobase. This method consists of the coupling reactions of the reversible nucleoside degradation pathway and energy generation through the yeast glycolytic pathway.

Results

Using E. coli that co-express deoxyriboaldolase and phosphopentomutase, a high amount of 2′-deoxyribonucleoside was produced with efficient energy transfer under phosphate-limiting reaction conditions. Keeping the nucleobase concentration low and the mixture at a low reaction temperature increased the yield of 2′-deoxyribonucleoside relative to the amount of added nucleobase, indicating that energy was efficiently generated from glucose via the yeast glycolytic pathway under these reaction conditions. Using a one-pot reaction in which small amounts of adenine, adenosine, and acetone-dried yeast were fed into the reaction, 75 mM of 2′-deoxyinosine, the deaminated product of 2′-deoxyadenosine, was produced from glucose (600 mM), acetaldehyde (250 mM), adenine (70 mM), and adenosine (20 mM) with a high yield relative to the total base moiety input (83%). Moreover, a variety of natural dNSs were further synthesized by introducing a base-exchange reaction into the process.

Conclusion

A critical common issue in energy-requiring bioprocess is fine control of phosphate concentration. We tried to resolve this problem, and provide the convenient recipe for establishment of energy-requiring bioprocesses. It is anticipated that the commercial demand for dNSs, which are primary metabolites that accumulate at very low levels in the metabolic pool, will grow. The development of an efficient production method for these compounds will have a great impact in both fields of applied microbiology and industry and will also serve as a good example of a microbial platform for energy-requiring bioprocesses.
Evaluation of the rapid diagnostic test CareStart pLDH Malaria (Pf-pLDH/pan-pLDH) for the diagnosis of malaria in a reference setting
Authors: Heutmekers Marloes , Gillet Philippe , Maltha Jessica , Scheirlinck Annelies , Cnops Lieselotte , Bottieau Emmanuel , Van Esbroeck Marjan , Jacobs Jan
Published: June 2012

Background

The present study evaluated CareStart pLDH Malaria, a three-band rapid diagnostic test detecting Plasmodium falciparum- specific parasite lactate dehydrogenase (Pf-pLDH) and pan Plasmodium-specific pLDH (pan-pLDH) in a reference setting.

Methods

CareStart pLDH was retrospectively and prospectively assessed with a panel of stored (n = 498) and fresh (n = 77) blood samples obtained in international travelers suspected of malaria. Both panels comprised all four Plasmodium species; the retrospective panel comprised also Plasmodium negative samples. The reference method was microscopy corrected by PCR. The prospective panel was run side-to-side with OptiMAL (Pf-pLDH/pan-pLDH) and SDFK60 (histidine-rich protein-2 (HRP-2)/pan-pLDH).

Results

In the retrospective evaluation, overall sensitivity for P. falciparum samples (n = 247) was 94.7%, reaching 98.7% for parasite densities > 1,000/μl. Most false negative results occurred among samples with pure gametocytaemia (2/12, 16.7%) and at parasite densities ≤ 100/μl (7/12, 58.3%). None of the Plasmodium negative samples (n = 96) showed visible test lines. Sensitivities for Plasmodium vivax (n = 70), Plasmodium ovale (n = 69) and Plasmodium malariae (n = 16) were 74.3%, 31.9% and 25.0% respectively. Wrong species identification occurred in 10 (2.5%) samples and was mainly due to P. vivax samples reacting with the Pf-pLDH test line. Overall, Pf-pLDH test lines showed higher line intensities compared to the pan-pLDH lines (67.9% and 23.0% medium and strong line intensities for P. falciparum). In the prospective panel (77 Plasmodium-positive samples), CareStart pLDH showed higher sensitivities for P. falciparum compared to OptiMAL (p = 0.008), lower sensitivities for P. falciparum as compare to SDFK60 (although not reaching statistical significance, p = 0.08) and higher sensitivities for P. ovale c ompared to both OptiMAL (p = 0.03) and SDFK60 (p = 0.01). Inter-observer and test reproducibility were good to excellent.

Conclusion

CareStart pLDH performed excellent for the detection of P. falciparum, well for P. vivax, but poor for P. ovale and P. malariae.
Quantitative characterization of agglomerates and aggregates of pyrogenic and precipitated amorphous silica nanomaterials by transmission electron microscopy
Authors: De Temmerman Pieter-Jan , Van Doren Elke , Verleysen Eveline , Van der Stede Yves , Francisco Michel Abi Daoud , Mast Jan
Published: June 2012

Background

The interaction of a nanomaterial (NM) with a biological system depends not only on the size of its primary particles but also on the size, shape and surface topology of its aggregates and agglomerates. A method based on transmission electron microscopy (TEM), to visualize the NM and on image analysis, to measure detected features quantitatively, was assessed for its capacity to characterize the aggregates and agglomerates of precipitated and pyrogenic synthetic amorphous silicon dioxide (SAS), or silica, NM.

Results

Bright field (BF) TEM combined with systematic random imaging and semi-automatic image analysis allows measuring the properties of SAS NM quantitatively. Automation allows measuring multiple and arithmetically complex parameters simultaneously on high numbers of detected particles. This reduces operator-induced bias and assures a statistically relevant number of measurements, avoiding the tedious repetitive task of manual measurements. Access to multiple parameters further allows selecting the optimal parameter in function of a specific purpose.

Using principle component analysis (PCA), twenty-three measured parameters were classified into three classes containing measures for size, shape and surface topology of the NM.

Conclusion

The presented method allows a detailed quantitative characterization of NM, like dispersions of precipitated and pyrogenic SAS based on the number-based distributions of their mean diameter, sphericity and shape factor.
Transient and intensive pharmacological immunosuppression fails to improve AAV-based liver gene transfer in non-human primates
Authors: Unzu Carmen , Hervás-Stubbs Sandra , Sampedro Ana , Mauleón Itsaso , Mancheño Uxua , Alfaro Carlos , de Salamanca Rafael Enríquez , Benito Alberto , Beattie Stuart G , Petry Harald , Prieto Jesús , Melero Ignacio , Fontanellas Antonio
Published: June 2012

Background

Adeno-associated vectors (rAAV) have been used to attain long-term liver gene expression. In humans, the cellular immune response poses a serious obstacle for transgene persistence while neutralizing humoral immunity curtails re-administration. Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria) benefits from liver gene transfer in mouse models and clinical trials are about to begin. In this work, we sought to study in non-human primates the feasibility of repeated gene-transfer with intravenous administration of rAAV5 vectors under the effects of an intensive immunosuppressive regimen and to analyze its ability to circumvent T-cell immunity and thereby prolong transgene expression.

Methods

Three female Macaca fascicularis were intravenously injected with 1x1013 genome copies/kg of rAAV5 encoding the human PBGD. Mycophenolate mofetil (MMF), anti-thymocyte immunoglobulin, methylprednisolone, tacrolimus and rituximab were given in combination during 12 weeks to block T- and B-cell mediated adaptive immune responses in two macaques. Immunodeficient and immunocompetent mice were intravenously injected with 5x1012 genome copies/kg of rAAV5-encoding luciferase protein. Forty days later MMF, tacrolimus and rituximab were daily administrated to ascertain whether the immunosuppressants or their metabolites could interfere with transgene expression.

Results

Macaques given a rAAV5 vector encoding human PBGD developed cellular and humoral immunity against viral capsids but not towards the transgene. Anti-AAV humoral responses were attenuated during 12 weeks but intensely rebounded following cessation of the immunosuppressants. Accordingly, subsequent gene transfer with a rAAV5 vector encoding green fluorescent protein was impossible. One macaque showed enhanced PBGD expression 25 weeks after rAAV5-pbgd administration but overexpression had not been detected while the animal was under immunosuppression. As a potential explanation, MMF decreases transgene expression in mouse livers that had been successfully transduced by a rAAV5 several weeks before MMF onset. Such a silencing effect was independent of AAV complementary strand synthesis and requires an adaptive immune system.

Conclusions

These results indicate that our transient and intensive pharmacological immunosuppression fails to improve AAV5-based liver gene transfer in non-human primates. The reasons include an incomplete restraint of humoral immune responses to viral capsids that interfere with repeated gene transfer in addition to an intriguing MMF-dependent drug-mediated interference with liver transgene expression.
Synthesis and electrical property of metal/ZnO coaxial nanocables
Authors: Li Zhi , Wang Guanzhong , Yang Qianhui , Shao Zhibin , Wang Yang
Published: June 2012

Ag/ZnO and Cu/ZnO coaxial nanocables were fabricated using AgNO3 or copper foil as source materials by the vapor-liquid-solid process. The coaxial nanocables consist of a crystalline metallic Ag or Cu core and a semiconductor ZnO shell. The evolution of the Ag/ZnO products having different morphologies was investigated by stopping the heating at different temperatures. The diameters of the Ag/ZnO nanocables and the Ag cores could be modulated by changing Ag ratio in the source. The electrical characteristics of the Ag/ZnO contact and the influence of annealing reveal a Schottky diode behavior for a single Ag/ZnO nanocable device. The nanocables with uniform shape and controlled size are expected to provide a new choice in various applications of biological detection, nanothermometer, and photocatalysis.
The magnetic-nanofluid heat pipe with superior thermal properties through magnetic enhancement
Authors: Chiang Yuan-Ching , Chieh Jen-Jie , Ho Chia-Che
Published: June 2012

This study developed a magnetic-nanofluid (MNF) heat pipe (MNFHP) with magnetically enhanced thermal properties. Its main characteristic was additional porous iron nozzle in the evaporator and the condenser to form a unique flowing pattern of MNF slug and vapor, and to magnetically shield the magnet attraction on MNF flowing. The results showed that an optimal thermal conductivity exists in the applied field of 200 Oe. Furthermore, the minor thermal performance of MNF at the condenser limited the thermal conductivity of the entire MNFHP, which was 1.6 times greater than that filled with water for the input power of 60 W. The feasibilities of an MNFHP with the magnetically enhanced heat transfer and the ability of vertical operation were proved for both a promising heat-dissipation device and the energy architecture integrated with an additional energy system.
Geraghty-type theorems in modular metric spaces with an application to partial differential equation
Authors: Chaipunya Parin , Je Cho Yeol , Kumam Poom
Published: June 2012

In this article, we prove some fixed point theorems of Geraghty-type concerning the existence and uniqueness of fixed points under the setting of modular metric spaces. Also, we give an application of our main results to establish the existence and uniqueness of a solution to a nonhomogeneous linear parabolic partial differential equation in the last section.

Mathematics Subject Classification (2010): 47H10, 54H25, 35K15.
Insight into hypoglycemia in pediatric type 1 diabetes mellitus
Authors: Lehecka Kimberly E , Renukuntla Venkat S , Heptulla Rubina A
Published: June 2012

Hypoglycemia is a common complication of insulin treatment in type 1 diabetes mellitus and can occur in any patient with diabetes when glucose consumption exceeds supply. Many studies have been done to elucidate those factors that predict severe hypoglycemia: younger age, longer duration of diabetes, lower HgbA1c, higher insulin dose, lower Body Mass Index, male gender, Caucasian race, underinsurance or low socioeconomic status, and the presence of psychiatric disorders. Hypoglycemia can affect patients' relationships, occupation, and daily activities such as driving. However, one of the greatest impacts is patients' fear of severe hypoglycemic events, which is a limiting factor in the optimization of glycemic control. Therefore, the importance of clinicians’ ability to identify those patients at greatest risk for hypoglycemic events is two-fold: 1) Patients at greatest risk may be counseled as such and offered newer therapies and monitoring technologies to prevent hypoglycemic events. 2) Patients at lower risk may be reassured and encouraged to improve their glycemic control. Since the risk of long-term complications with poor blood glucose control outweighs the risks of hypoglycemia with good blood glucose control, patients should be encouraged to aim for glucose concentrations in the physiologic range pre- and post-prandially. Advancements in care, including multiple daily injection therapy with analog insulin, continuous subcutaneous insulin infusion, and continuous glucose monitoring, have each subsequently improved glycemic control and decreased the risk of severe hypoglycemia.
Low level genome mistranslations deregulate the transcriptome and translatome and generate proteotoxic stress in yeast
Authors: Paredes João A , Carreto Laura , Simões João , Bezerra Ana R , Gomes Ana C , Santamaria Rodrigo , Kapushesky Misha , Moura Gabriela R , Santos Manuel AS
Published: June 2012

Background

Organisms use highly accurate molecular processes to transcribe their genes and a variety of mRNA quality control and ribosome proofreading mechanisms to maintain intact the fidelity of genetic information flow. Despite this, low level gene translational errors induced by mutations and environmental factors cause neurodegeneration and premature death in mice and mitochondrial disorders in humans. Paradoxically, such errors can generate advantageous phenotypic diversity in fungi and bacteria through poorly understood molecular processes.

Results

In order to clarify the biological relevance of gene translational errors we have engineered codon misreading in yeast and used profiling of total and polysome-associated mRNAs, molecular and biochemical tools to characterize the recombinant cells. We demonstrate here that gene translational errors, which have negligible impact on yeast growth rate down-regulate protein synthesis, activate the unfolded protein response and environmental stress response pathways, and down-regulate chaperones linked to ribosomes.

Conclusions

We provide the first global view of transcriptional and post-transcriptional responses to global gene translational errors and we postulate that they cause gradual cell degeneration through synergistic effects of overloading protein quality control systems and deregulation of protein synthesis, but generate adaptive phenotypes in unicellular organisms through activation of stress cross-protection. We conclude that these genome wide gene translational infidelities can be degenerative or adaptive depending on cellular context and physiological condition.
Transforming growth factor β1-induced astrocyte migration is mediated in part by activating 5-lipoxygenase and cysteinyl leukotriene receptor 1
Authors: Huang Xue-Qin , Zhang Xia-Yan , Wang Xiao-Rong , Yu Shu-Ying , Fang San-Hua , Lu Yun-Bi , Zhang Wei-Ping , Wei Er-Qing
Published: June 2012

Background

Transforming growth factor-β1 (TGF-β1) is an important regulator of cell migration and plays a role in the scarring response in injured brain. It is also reported that 5-lipoxygenase (5-LOX) and its products, cysteinyl leukotrienes (CysLTs, namely LTC4, LTD4and LTE4), as well as cysteinyl leukotriene receptor 1 (CysLT1R) are closely associated with astrocyte proliferation and glial scar formation after brain injury. However, how these molecules act on astrocyte migration, an initial step of the scarring response, is unknown. To clarify this, we determined the roles of 5-LOX and CysLT1R in TGF-β1-induced astrocyte migration.

Methods

In primary cultures of rat astrocytes, the effects of TGF-β1 and CysLT receptor agonists on migration and proliferation were assayed, and the expression of 5-LOX, CysLT receptors and TGF-β1 was detected. 5-LOX activation was analyzed by measuring its products (CysLTs) and applying its inhibitor. The role of CysLT1R was investigated by applying CysLT receptor antagonists and CysLT1R knockdown by small interfering RNA (siRNA). TGF-β1 release was assayed as well.

Results

TGF-β1-induced astrocyte migration was potentiated by LTD4, but attenuated by the 5-LOX inhibitor zileuton and the CysLT1R antagonist montelukast. The non-selective agonist LTD4at 0.1 to 10 nM also induced a mild migration; however, the selective agonist N-methyl-LTC4and the selective antagonist Bay cysLT2 for CysLT2R had no effects. Moreover, CysLT1R siRNA inhibited TGF-β1- and LTD4-induced astrocyte migration by down-regulating the expression of this receptor. However, TGF-β1 and LTD4at various concentrations did not affect astrocyte proliferation 24 h after exposure. On the other hand, TGF-β1 increased 5-LOX expression and the production of CysLTs, and up-regulated CysLT1R (not CysLT2R), while LTD4and N-methyl-LTC4did not affect TGF-β1 expression and release.

Conclusions

TGF-β1-induced astrocyte migration is, at least in part, mediated by enhanced endogenous CysLTs through activating CysLT1R. These findings indicate that the interaction between the cytokine TGF-β1 and the pro-inflammatory mediators CysLTs in the regulation of astrocyte function is relevant to glial scar formation.
The function and evolution of the restriction factor viperin in primates was not driven by lentiviruses
Authors: Lim Efrem S , Wu Lily I , Malik Harmit S , Emerman Michael
Published: June 2012

Background

Viperin, also known as RSAD2, is an interferon-inducible protein that potently restricts a broad range of different viruses such as influenza, hepatitis C virus, human cytomegalovirus and West Nile virus. Viperin is thought to affect virus budding by modification of the lipid environment within the cell. Since HIV-1 and other retroviruses depend on lipid domains of the host cell for budding and infectivity, we investigated the possibility that Viperin also restricts human immunodeficiency virus and other retroviruses.

Results

Like other host restriction factors that have a broad antiviral range, we find that viperin has also been evolving under positive selection in primates. The pattern of positive selection is indicative of Viperin's escape from multiple viral antagonists over the course of primate evolution. Furthermore, we find that Viperin is interferon-induced in HIV primary target cells. We show that exogenous expression of Viperin restricts the LAI strain of HIV-1 at the stage of virus release from the cell. Nonetheless, the effect of Viperin restriction is highly strain-specific and does not affect most HIV-1 strains or other retroviruses tested. Moreover, knockdown of endogenous Viperin in a lymphocytic cell line did not significantly affect the spreading infection of HIV-1.

Conclusion

Despite positive selection having acted on Viperin throughout primate evolution, our findings indicate that Viperin is not a major restriction factor against HIV-1 and other retroviruses. Therefore, other viral lineages are likely responsible for the evolutionary signatures of positive selection in viperin among primates.
Event-based internet biosurveillance: relation to epidemiological observation
Authors: Nelson Noele P , Yang Li , Reilly Aimee R , Hardin Jessica E , Hartley David M
Published: June 2012

Background

The World Health Organization (WHO) collects and publishes surveillance data and statistics for select diseases, but traditional methods of gathering such data are time and labor intensive. Event-based biosurveillance, which utilizes a variety of Internet sources, complements traditional surveillance. In this study we assess the reliability of Internet biosurveillance and evaluate disease-specific alert criteria against epidemiological data.

Methods

We reviewed and compared WHO epidemiological data and Argus biosurveillance system data for pandemic (H1N1) 2009 (April 2009 – January 2010) from 8 regions and 122 countries to: identify reliable alert criteria among 15 Argus-defined categories; determine the degree of data correlation for disease progression; and assess timeliness of Internet information.

Results

Argus generated a total of 1,580 unique alerts; 5 alert categories generated statistically significant (p < 0.05) correlations with WHO case count data; the sum of these 5 categories was highly correlated with WHO case data (r = 0.81, p < 0.0001), with expected differences observed among the 8 regions. Argus reported first confirmed cases on the same day as WHO for 21 of the first 64 countries reporting cases, and 1 to 16 days (average 1.5 days) ahead of WHO for 42 of those countries.

Conclusion

Confirmed pandemic (H1N1) 2009 cases collected by Argus and WHO methods returned consistent results and confirmed the reliability and timeliness of Internet information. Disease-specific alert criteria provide situational awareness and may serve as proxy indicators to event progression and escalation in lieu of traditional surveillance data; alerts may identify early-warning indicators to another pandemic, preparing the public health community for disease events.
Salt overload in fructose-fed insulin-resistant rats decreases paraoxonase-1 activity
Authors: Dornas Waleska Cláudia , de Lima Wanderson Geraldo , dos Santos Rinaldo Cardoso , de Souza Melina Oliveira , Silva Maísa , Diniz Mirla Fiuza , Silva Marcelo Eustáquio
Published: June 2012

Paraoxonase 1 (PON1) is a HDL-associated esterase/lactonase and its activity is inversely related to the risk of cardiovascular diseases. The aim of the present study was to evaluate the effect of a high-salt diet on serum PON1 activity in fructose-fed insulin-resistant rats. Adult male Fischer rats were initially divided into two groups. Control (CON), which received a normal salt diet and drinking water throughout the study; high fructose (HF), which received a normal salt diet and 20% fructose supplemented drinking water. After 10 weeks, half of the animals from HF group were randomly switched to a high-salt diet and 20% fructose supplemented drinking water (HFS) for more 10 weeks. Serum PON1 activity was determined by synthetic substrate phenyl acetate. HFS rats showed markedly decreased PON1 activity (HFS rats, 44.3 ± 14.4 g/dL versus CON rats, 64.4 ± 13.3 g/dL, P < 0.05) as compared to controls. In parallel, the level of oxidative stress, as indicated by thiobarbituric acid reactive substances (TBARS), was increased in HFS rats by 1.2-fold in the liver in relation to controls and was negatively correlated with PON activity. Differential leukocyte counts in blood showed a significant change in lymphocytes and monocytes profile. In conclusion, these results show that PON1 activity is decreased in fructose-fed insulin-resistant rats on a high-salt diet, which may be associated with increased oxidative stress, leading to inflammation.
Painful Nerve Injury Increases Plasma Membrane Ca2+-ATPase Activity in Axotomized Sensory Neurons
Authors: Gemes Geza , Oyster Katherine D , Pan Bin , Wu Hsiang-En , Bangaru Madhavi Latha Yadav , Tang Qingbo , Hogan Quinn H
Published: June 2012

Background:

The plasma membrane Ca2+-ATPase (PMCA) is the principal means by which sensory neurons expel Ca2+ and thereby regulate the concentration of cytoplasmic Ca2+ and the processes controlled by this critical second messenger. We have previously found that painful nerve injury decreases resting cytoplasmic Ca2+ levels and activity-induced cytoplasmic Ca2+ accumulation in axotomized sensory neurons. Here we examine the contribution of PMCA after nerve injury in a rat model of neuropathic pain.

Results:

PMCA function was isolated in dissociated sensory neurons by blocking intracellular Ca2+ sequestration with thapsigargin, and cytoplasmic Ca2+ concentration was recorded with Fura-2 fluorometry. Compared to control neurons, the rate at which depolarization-induced Ca2+ transients resolved was increased in axotomized neurons after spinal nerve ligation, indicating accelerated PMCA function. Electrophysiological recordings showed that blockade of PMCA by vanadate prolonged the action potential afterhyperpolarization, and also decreased the rate at which neurons could fire repetitively.

Conclusion:

We found that PMCA function is elevated in axotomized sensory neurons, which contributes to neuronal hyperexcitability. Accelerated PMCA function in the primary sensory neuron may contribute to the generation of neuropathic pain, and thus its modulation could provide a new pathway for peripheral treatment of post-traumatic neuropathic pain.
Effect of intermittent exposure to ethanol and MDMA during adolescence on learning and memory in adult mice
Authors: Vidal-Infer Antonio , Aguilar Maria A. , Miñarro Jose , Rodríguez-Arias Marta
Published: June 2012

Background

Heavy binge drinking is increasingly frequent among adolescents, and consumption of 3,4-methylenedioxymethamphetamine (MDMA) is often combined with ethanol (EtOH). The long-lasting effects of intermittent exposure to EtOH and MDMA during adolescence on learning and memory were evaluated in adult mice using the Hebb-Williams maze.

Methods

Adolescent OF1 mice were exposed to EtOH (1.25 g/kg) on two consecutive days at 48-h intervals over a 14-day period (from PD 29 to 42). MDMA (10 or 20 mg/kg) was injected twice daily at 4-h intervals over two consecutive days, and this schedule was repeated six days later (PD 33, 34, 41 and 42), resulting in a total of eight injections. Animals were initiated in the Hebb-Williams maze on PND 64. The concentration of brain monoamines in the striatum and hippocampus was then measured.

Results

At the doses employed, both EtOH and MDMA, administered alone or together, impaired learning in the Hebb-Williams maze, as treated animals required more time to reach the goal than their saline-treated counterparts. The groups treated during adolescence with EtOH, alone or plus MDMA, also presented longer latency scores and needed more trials to reach the acquisition criterion score. MDMA induced a decrease in striatal DA concentration, an effect that was augmented by the co-administration of EtOH. All the treatment groups displayed an imbalance in the interaction DA/serotonin.

Conclusions

The present findings indicate that the developing brain is highly vulnerable to the damaging effects of EtOH and/or MDMA, since mice receiving these drugs in a binge pattern during adolescence exhibit impaired learning and memory in adulthood.
Primary Intravascular large B-cell lymphoma of lung: a report of one case and review
Authors: Yu Hui , Chen Gang , Zhang Rongxuan , Jin Xiaolong
Published: June 2012

Objective

To investigate the clinicopathological features of primary intravascular large B-cell lymphoma of lung.

Methods

A case of primary pulmonary intravascular large B-cell lymphoma was analysed in histopathology and immunophenotype.

Results

The patient is a 42-year-old female who had cough for one year. Computed tomography showed ground-glass opacities and small nodules in bilateral lung fields. Histopathology demonstrated accumulation of similar sized neoplastic cells within alveolar capillaries, widening the alveolar septae. The alveolar structure sustained in part of districtions. Immunohistologically, the tumor cells were positive for CD20 and negative for CD3,CK, which were similar to the diffuse large B-cell lymphoma.

Conclusions

Intravascular large B-cell lymphoma is an uncommon type of non-Hodgkin’s lymphoma. Primary pulmonary presentation is even more rare. The diagnosis is based on the histopathology and immunohistochemistry.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2076991810705433.
Effect of high contents of dietary animal-derived protein or carbohydrates on canine faecal microbiota
Authors: Hang Ingrid , Rinttila Teemu , Zentek Jürgen , Kettunen Anu , Alaja Susanna , Apajalahti Juha , Harmoinen Jaana , de Vos Willem M , Spillmann Thomas
Published: June 2012

Background

Considerable evidence suggests that food impacts both the gastro-intestinal (GI) function and the microbial ecology of the canine GI tract. The aim of this study was to evaluate the influence of high-carbohydrate (HC), high-protein (HP) and dry commercial (DC) diets on the canine colonic microbiota in Beagle dogs. Diets were allocated according to the Graeco-Latin square design. For this purpose, microbial DNA was isolated from faecal samples and separated by density gradient centrifugation, resulting in specific profiling based on the guanine-cytosine content (%G + C). In addition, 16 S rRNA gene amplicons were obtained from the most abundant %G + C peaks and analysed by sequence analysis, producing a total of 720 non-redundant sequences (240 sequences per diet).

Results

The DC diet sample showed high abundance of representatives of the orders Clostridiales, Lactobacillales, Coriobacteriales and Bacteroidales. Sequence diversity was highest for DC diet samples and included representatives of the orders Lactobacillales and Bacteroidales, which were not detected in samples from the HP and HC diets. These latter two diets also had reduced levels of representatives of the family Lachnospiraceae, specifically Clostridial cluster XIVa. The HC diet favoured representatives of the order Erysipelotrichales, more specifically the Clostridial cluster XVIII, while the HP diet favoured representatives of the order Fusobacteriales.

Conclusions

This study detected Coriobacteriales in dog faeces, possibly due to the non-selective nature of the %G + C profiling method used in combination with sequencing. Moreover, our work demonstrates that the effect of diet on faecal microbiota can be explained based on the metabolic properties of the detected microbial taxa.
Impact of external sources of infection on the dynamics of bovine tuberculosis in modelled badger populations
Authors: Hardstaff Joanne L , Bulling Mark T , Marion Glenn , Hutchings Michael R , White Piran C L
Published: June 2012

Background

The persistence of bovine TB (bTB) in various countries throughout the world is enhanced by the existence of wildlife hosts for the infection. In Britain and Ireland, the principal wildlife host for bTB is the badger (Meles meles). The objective of our study was to examine the dynamics of bTB in badgers in relation to both badger-derived infection from within the population and externally-derived, trickle-type, infection, such as could occur from other species or environmental sources, using a spatial stochastic simulation model.

Results

The presence of external sources of infection can increase mean prevalence and reduce the threshold group size for disease persistence. Above the threshold equilibrium group size of 6–8 individuals predicted by the model for bTB persistence in badgers based on internal infection alone, external sources of infection have relatively little impact on the persistence or level of disease. However, within a critical range of group sizes just below this threshold level, external infection becomes much more important in determining disease dynamics. Within this critical range, external infection increases the ratio of intra- to inter-group infections due to the greater probability of external infections entering fully-susceptible groups. The effect is to enable bTB persistence and increase bTB prevalence in badger populations which would not be able to maintain bTB based on internal infection alone.

Conclusions

External sources of bTB infection can contribute to the persistence of bTB in badger populations. In high-density badger populations, internal badger-derived infections occur at a sufficient rate that the additional effect of external sources in exacerbating disease is minimal. However, in lower-density populations, external sources of infection are much more important in enhancing bTB prevalence and persistence. In such circumstances, it is particularly important that control strategies to reduce bTB in badgers include efforts to minimise such external sources of infection.
Designing an implementation strategy to improve interprofessional shared decision making in sciatica: study protocol of the DISC study
Authors: Hofstede Stefanie N , Marang-van de Mheen Perla J , Assendelft Willem JJ , Vleggeert-Lankamp Carmen LA , Stiggelbout Anne M , Vroomen Patrick CAJ , van den Hout Wilbert B , Vliet Vlieland Thea PM , van Bodegom-Vos Leti ,   for the DISC study group
Published: June 2012

Background

Sciatica is a common condition worldwide that is characterized by radiating leg pain and regularly caused by a herniated disc with nerve root compression. Sciatica patients with persisting leg pain after six to eight weeks were found to have similar clinical outcomes and associated costs after prolonged conservative treatment or surgery at one year follow-up. Guidelines recommend that the team of professionals involved in sciatica care and patients jointly decide about treatment options, so-called interprofessional shared decision making (SDM). However, there are strong indications that SDM for sciatica patients is not integrated in daily practice. We designed a study aiming to explore the barriers and facilitators associated with the everyday embedding of SDM for sciatica patients. All related relevant professionals and patients are involved to develop a tailored strategy to implement SDM for sciatica patients.

Methods

The study consists of two phases: identification of barriers and facilitators and development of an implementation strategy. First, barriers and facilitators are explored using semi-structured interviews among eight professionals of each (para)medical discipline involved in sciatica care (general practitioners, physical therapists, neurologists, neurosurgeons, and orthopedic surgeons). In addition, three focus groups will be conducted among patients. Second, the identified barriers and facilitators will be ranked using a questionnaire among a representative Dutch sample of 200 GPs, 200 physical therapists, 200 neurologists, all 124 neurosurgeons, 200 orthopedic surgeons, and 100 patients. A tailored team-based implementation strategy will be developed based on the results of the first phase using the principles of intervention mapping and an expert panel.

Discussion

Little is known about effective strategies to increase the uptake of SDM. Most implementation strategies only target a single discipline, whereas multiple disciplines are involved in SDM among sciatica patients. The results of this study can be used as an example for implementing SDM in other patient groups receiving multidisciplinary complex care (e.g., elderly) and can be generalized to other countries with similar context, thereby contributing to a worldwide increase of SDM in preference sensitive choices.
Increased Artemis levels confer radioresistance to both high and low LET radiation exposures
Authors: Sridharan Deepa M , Whalen Mary K , Almendrala Donna , Cucinotta Francis A , Kawahara Misako , Yannone Steven M , Pluth Janice M
Published: June 2012

Background

Artemis has a defined role in V(D)J recombination and has been implicated in the repair of radiation induced double-strand breaks. However the exact function(s) of Artemis in DNA repair and its preferred substrate(s) in vivo remain undefined. Our previous work suggests that Artemis is important for the repair of complex DNA damage like that inflicted by high Linear Energy Transfer (LET) radiation. To establish the contribution of Artemis in repairing DNA damage caused by various radiation qualities, we evaluated the effect of over-expressing Artemis on cell survival, DNA repair, and cell cycle arrest after exposure to high and low LET radiation.

Results

Our data reveal that Artemis over-expression confers marked radioprotection against both types of radiation, although the radioprotective effect was greater following high LET radiation. Inhibitor studies reveal that the radioprotection imparted by Artemis is primarily dependent on DNA-PK activity, and to a lesser extent on ATM kinase activity. Together, these data suggest a DNA-PK dependent role for Artemis in the repair of complex DNA damage.

Conclusions

These findings indicate that Artemis levels significantly influence radiation toxicity in human cells and suggest that Artemis inhibition could be a practical target for adjuvant cancer therapies.