bluuebunny/crossref_metadata_2025 huggingface dataset:
‘No good for shovelling snow and carrying firewood’: Social representations of computers and the internet by elderly Finnish non-users
Authors: Hakkarainen Päivi
Published: May 2012

This study explores elderly people’s refusal to use the computer and the internet from the perspective of social representations by seeking answers to the following questions: How do the respondents classify the computer and the internet? What kind of images do they use to depict the computer and the internet? How do the social representations of the computer and the internet express the respondents’ distinct identities, interests, history and culture? The research data consist of written accounts by Finnish elderly people living in non-urban environments. Their social representations can be summarized as follows: the computer and the internet are useless and risky ‘tools and things’ that threaten one’s freedom, lifestyle, health and security as well as create differences between users and non-users. The study shows how some elderly people’s distinct identities, interests, history and culture may limit their motivation and capacity to welcome and use the computer.
Of Victims and Markets
Authors: Bass Jordan R. , Newman Joshua I. , Giardina Michael D.
Published: May 2012

This article addresses the market logics on display at Penn State University in response to the Jerry Sandusky scandal, especially with respect to the idea of civic branding and community formation. The intersecting vectors of the corporate university, neoliberalism, and physical culture are highlighted to explain such a response. Responses to the scandal are also addressed in light of similar discourses of victimology present in the larger Wall Street financial sector.
At Penn State, a Bitter Reckoning
Authors: Bérubé Michael
Published: May 2012

The essay looks at the Sandusky scandal from the perspective of Penn State faculty members, and places it in the context of the erosion of shared governance and faculty oversight of athletic programs at Penn State and elsewhere.
Illuminating the Effects of Dynamic Lighting on Student Learning
Authors: Mott Michael S. , Robinson Daniel H. , Walden Ashley , Burnette Jodie , Rutherford Angela S.
Published: May 2012

Light is universally understood as essential to the human condition. Yet light quality varies substantially in nature and in controlled environments leading to questions of which artificial light characteristics facilitate maximum learning. Recent research has examined lighting variables of color temperature, and illumination for affecting sleep, mood, focus, motivation, concentration, and work and school performance. This has resulted in artificial light systems intended to support human beings in their actualization through dynamic lighting technology allowing for different lighting conditions per task. A total of 84 third graders were exposed to either focus (6000K-100fc average maintained) or normal lighting. Focus lighting led to a higher percentage increase in oral reading fluency performance (36%) than did control lighting (17%). No lighting effects were found for motivation or concentration, possibly attributable to the younger age level of respondents as compared with European studies. These findings illuminate the need for further research on artificial light and learning.
Directional Color Doppler Aids the 2D and 3D Prenatal Diagnosis of Cleft Lip and Palate With Antenatal Single-Shot Fast-Spin Echo Magnetic Resonance Imaging Confirmation
Authors: Tonni Gabriele , Lituania Mario
Published: May 2012

Standard 2D sonography has variable success in the prenatal diagnosis of cleft lip combined with cleft palate. A case is presented that demonstrates the added value of 3D sonography plus color Doppler imaging in confirming this diagnosis. Additional techniques such as the flipped-face view, the reverse-face view, and the oblique-face view are discussed as further enhancements to the prenatal sonographic study of the fetal palate.
Platelets support a protective immune response to LCMV by preventing splenic necrosis
Authors: Loria Gilbert David , Romagnoli Pablo A. , Moseley Nelson B. , Rucavado Alexandra , Altman John D.
Published: May 2012

Key Points

Levels of circulating platelets determine the degree of pathology observed during arenavirus infections. While moderate platelet drops result in deficient immune control of an LCMV infection, severe platelet-drops result in systemic hemorrhages.
How I treat pediatric acute myeloid leukemia
Authors: Rubnitz Jeffrey E.
Published: May 2012

Acute myeloid leukemia is a heterogeneous disease that accounts for approximately 20% of acute leukemias in children and adolescents. Despite the lack of targeted therapy for most subtypes and a dearth of new agents, survival rates have reached approximately 60% for children treated on clinical trials in developed countries. Most of the advances have been accomplished by better risk classification, the implementation of excellent supportive care measures, adaptation of therapy on the basis of each patient's response to therapy, and improvements in allogeneic hematopoietic stem cell transplantation. However, it is unlikely that further gains can be made through these measures alone. In this regard, high-resolution, genome-wide analyses have led to greater understanding of the pathogenesis of this disease and the identification of molecular abnormalities that are potential targets of new therapies. The development of molecularly targeted agents, some of which are already in clinical trials, holds great promise for the future.
The footprint of metabolism in the organization of mammalian genomes
Authors: Berná Luisa , Chaurasia Ankita , Angelini Claudia , Federico Concetta , Saccone Salvatore , D'Onofrio Giuseppe
Published: May 2012

Background

At present five evolutionary hypotheses have been proposed to explain the great variability of the genomic GC content among and within genomes: the mutational bias, the biased gene conversion, the DNA breakpoints distribution, the thermal stability and the metabolic rate. Several studies carried out on bacteria and teleostean fish pointed towards the critical role played by the environment on the metabolic rate in shaping the base composition of genomes. In mammals the debate is still open, and evidences have been produced in favor of each evolutionary hypothesis. Human genes were assigned to three large functional categories (as well as to the corresponding functional classes) according to the KOG database: (i) information storage and processing, (ii) cellular processes and signaling, and (iii) metabolism. The classification was extended to the organisms so far analyzed performing a reciprocal Blastp and selecting the best reciprocal hit. The base composition was calculated for each sequence of the whole CDS dataset.

Results

The GC3 level of the above functional categories was increasing from (i) to (iii). This specific compositional pattern was found, as footprint, in all mammalian genomes, but not in frog and lizard ones. Comparative analysis of human versus both frog and lizard functional categories showed that genes involved in the metabolic processes underwent the highest GC3 increment. Analyzing the KOG functional classes of genes, again a well defined intra-genomic pattern was found in all mammals. Not only genes of metabolic pathways, but also genes involved in chromatin structure and dynamics, transcription, signal transduction mechanisms and cytoskeleton, showed an average GC3 level higher than that of the whole genome. In the case of the human genome, the genes of the aforementioned functional categories showed a high probability to be associated with the chromosomal bands.

Conclusions

In the light of different evolutionary hypotheses proposed so far, and contributing with different potential to the genome compositional heterogeneity of mammalian genomes, the one based on the metabolic rate seems to play not a minor role. Keeping in mind similar results reported in bacteria and in teleosts, the specific compositional patterns observed in mammals highlight metabolic rate as unifying factor that fits over a wide range of living organisms.
Phylogenomic analysis of UDP glycosyltransferase 1 multigene family in Linum usitatissimum identified genes with varied expression patterns
Authors: Barvkar Vitthal T , Pardeshi Varsha C , Kale Sandip M , Kadoo Narendra Y , Gupta Vidya S
Published: May 2012

Background

The glycosylation process, catalyzed by ubiquitous glycosyltransferase (GT) family enzymes, is a prevalent modification of plant secondary metabolites that regulates various functions such as hormone homeostasis, detoxification of xenobiotics and biosynthesis and storage of secondary metabolites. Flax (Linum usitatissimum L.) is a commercially grown oilseed crop, important because of its essential fatty acids and health promoting lignans. Identification and characterization of UDP glycosyltransferase (UGT) genes from flax could provide valuable basic information about this important gene family and help to explain the seed specific glycosylated metabolite accumulation and other processes in plants. Plant genome sequencing projects are useful to discover complexity within this gene family and also pave way for the development of functional genomics approaches.

Results

Taking advantage of the newly assembled draft genome sequence of flax, we identified 137 UDP glycosyltransferase (UGT) genes from flax using a conserved signature motif. Phylogenetic analysis of these protein sequences clustered them into 14 major groups (A-N). Expression patterns of these genes were investigated using publicly available expressed sequence tag (EST), microarray data and reverse transcription quantitative real time PCR (RT-qPCR). Seventy-three per cent of these genes (100 out of 137) showed expression evidence in 15 tissues examined and indicated varied expression profiles. The RT-qPCR results of 10 selected genes were also coherent with the digital expression analysis. Interestingly, five duplicated UGT genes were identified, which showed differential expression in various tissues. Of the seven intron loss/gain positions detected, two intron positions were conserved among most of the UGTs, although a clear relationship about the evolution of these genes could not be established. Comparison of the flax UGTs with orthologs from four other sequenced dicot genomes indicated that seven UGTs were flax diverged.

Conclusions

Flax has a large number of UGT genes including few flax diverged ones. Phylogenetic analysis and expression profiles of these genes identified tissue and condition specific repertoire of UGT genes from this crop. This study would facilitate precise selection of candidate genes and their further characterization of substrate specificities and in planta functions.
Comparative analyses reveal potential uses of Brachypodium distachyonas a model for cold stress responses in temperate grasses
Authors: Li Chuan , Rudi Heidi , Stockinger Eric J , Cheng Hongmei , Cao Moju , Fox Samuel E , Mockler Todd C , Westereng Bjørge , Fjellheim Siri , Rognli Odd Arne , Sandve Simen R
Published: May 2012

Background

Little is known about the potential of Brachypodium distachyon as a model for low temperature stress responses in Pooideae. The ice recrystallization inhibition protein (IRIP) genes, fructosyltransferase (FST) genes, and many C-repeat binding factor (CBF) genes are Pooideae specific and important in low temperature responses. Here we used comparative analyses to study conservation and evolution of these gene families in B. distachyon to better understand its potential as a model species for agriculturally important temperate grasses.

Results

Brachypodium distachyon contains cold responsive IRIP genes which have evolved through Brachypodium specific gene family expansions. A large cold responsive CBF3 subfamily was identified in B. distachyon, while CBF4 homologs are absent from the genome. No B. distachyon FST gene homologs encode typical core Pooideae FST-motifs and low temperature induced fructan accumulation was dramatically different in B. distachyon compared to core Pooideae species.

Conclusions

We conclude that B. distachyon can serve as an interesting model for specific molecular mechanisms involved in low temperature responses in core Pooideae species. However, the evolutionary history of key genes involved in low temperature responses has been different in Brachypodium and core Pooideae species. These differences limit the use of B. distachyon as a model for holistic studies relevant for agricultural core Pooideae species.
Identification of pneumonia and influenza deaths using the death certificate pipeline
Authors: Davis Kailah , Staes Catherine , Duncan Jeff , Igo Sean , Facelli Julio C
Published: May 2012

Background

Death records are a rich source of data, which can be used to assist with public surveillance and/or decision support. However, to use this type of data for such purposes it has to be transformed into a coded format to make it computable. Because the cause of death in the certificates is reported as free text, encoding the data is currently the single largest barrier of using death certificates for surveillance. Therefore, the purpose of this study was to demonstrate the feasibility of using a pipeline, composed of a detection rule and a natural language processor, for the real time encoding of death certificates using the identification of pneumonia and influenza cases as an example and demonstrating that its accuracy is comparable to existing methods.

Results

A Death Certificates Pipeline (DCP) was developed to automatically code death certificates and identify pneumonia and influenza cases. The pipeline used MetaMap to code death certificates from the Utah Department of Health for the year 2008. The output of MetaMap was then accessed by detection rules which flagged pneumonia and influenza cases based on the Centers of Disease and Control and Prevention (CDC) case definition. The output from the DCP was compared with the current method used by the CDC and with a keyword search. Recall, precision, positive predictive value and F-measure with respect to the CDC method were calculated for the two other methods considered here. The two different techniques compared here with the CDC method showed the following recall/ precision results: DCP: 0.998/0.98 and keyword searching: 0.96/0.96. The F-measure were 0.99 and 0.96 respectively (DCP and keyword searching). Both the keyword and the DCP can run in interactive form with modest computer resources, but DCP showed superior performance.

Conclusion

The pipeline proposed here for coding death certificates and the detection of cases is feasible and can be extended to other conditions. This method provides an alternative that allows for coding free-text death certificates in real time that may increase its utilization not only in the public health domain but also for biomedical researchers and developers.

Trial Registration

This study did not involved any clinical trials.
Interferon-α enhances antitumor activities of oncolytic adenovirus-mediated IL-24 expression in hepatocellular carcinoma
Authors: Wang Cong-Jun , Xiao Chao-Wen , You Tian-Geng , Zheng Ya-Xin , Gao Wei , Zhou Zhu-Qing , Chen Jun , Xue Xin-Bo , Fan Jia , Zhang Hui
Published: May 2012

Background

Hepatocellular carcinoma (HCC) has a dismal 5-year-survival rate of 10%, so novel strategies are warranted. IL-24 mediates anti-tumor activity reducing STAT3 expression, which suggests that interferon (IFN) alpha may augment tumor cell lysis and reduce angiogenesis. We investigated the antitumor activity of treatment with IFN-α, with the oncolytic adenovirus SG600-IL-24, or the combination of both in HCC in vitro and in vivo.

Results

RT-PCR, ELISA assay and Western-blot confirmed that the exogenous IL-24 gene was highly expressed in HCC cells infected with SG600-IL-24. Treatment with combined IFN-α and SG600-IL-24 suppressed growth and promoted apoptosis of the HepG2, MHCC97L, and HCCLM3 cell lines compared with the normal cell line L02. The combined therapy increased STAT1 and SOCS1 and apoptosis, but decreased the expression of the metastatic and angiogenic proteins MMP-2, XIAP, OPN, and VEGF, which are regulated by STAT3 in HCC cells in vitro. To assess the effects in vivo, the HCC cell line HCCLM3 was transplanted subcutaneously into the right flanks of nude mice. Mice in the IFN-α group, the SG600-IL-24 group, or the combined therapy group had significantly suppressed growth of the HCC xenografted tumors compared to the PBS control group of mice. Among the mice treated with the combination of IFN-α and SG600-IL-24, three of those eight mice had long-term survival and no evidence of a tumor. These mice also had decreased expression of the metastatic and angiogenic proteins MMP-2, XIAP, OPN, and VEGF.

Conclusions

The present study demonstrated for the first time the potential antitumor activity of IFN-α combined with the oncolytic adenovirus SG600-IL-24 in HCC both in vitro and in vivo, and suggests its further development as a potential candidate for HCC cancer gene therapy.
Impact of obesity control on circulating level of endothelial progenitor cells and angiogenesis in response to ischemic stimulation
Authors: Chen Yung-Lung , Chang Chia-Lo , Sun Cheuk-Kwan , Wu Chiung-Jen , Tsai Tzu-Hsien , Chung Sheng-Ying , Chua Sarah , Yeh Kuo-Ho , Leu Steve , Sheu Jiunn-Jye , Lee Fan-Yen , Yen Chia-Hung , Yip Hon-Kan
Published: May 2012

Background and aim

We tested the hypothesis that obesity reduced circulating number of endothelial progenitor cells (EPCs), angiogenic ability, and blood flow in ischemic tissue that could be reversed after obesity control.

Methods

8-week-old C57BL/6J mice (n = 27) were equally divided into group 1 (fed with 22-week control diet), group 2 (22-week high fat diet), and group 3 (14-week high fat diet, followed by 8-week control diet). Critical limb ischemia (CLI) was induced at week 20 in groups 2 and 3. The animals were sacrificed at the end of 22 weeks.

Results

Heart weight, body weight, abdominal fat weight, serum total cholesterol level, and fasting blood sugar were highest in group 2 (all p < 0.001). The numbers of circulating EPCs (C-kit/CD31+, Sca-1/KDR + and CXCR4/CD34+) were lower in groups 1 and 2 than in group 3 at 18 h after CLI induction (p < 0.03). The numbers of differentiated EPCs (C-kit/CD31+, CXCR4/CD34+ and CD133+) from adipose tissue after 14-day cultivation were also lowest in group 2 (p < 0.001). Protein expressions of VCAM-1, oxidative index, Smad3, and TGF-β were higher, whereas the Smad1/5 and BMP-2, mitochondrial cytochrome-C SDF-1α and CXCR4 were lower in group 2 than in groups 1 and 3 (all p < 0.02). Immunofluorescent staining of CD31+ and vWF + cells, the number of small vessel (<15 μm), and blood flow through Laser Doppler scanning of ischemic area were lower in group 2 compared to groups 1 and 3 on day 14 after CLI induction (all p < 0.001).

Conclusion

Obesity suppressed abilities of angiogenesis and recovery from CLI that were reversed by obesity control.
Predictive role of multiple gene alterations in response to cetuximab in metastatic colorectal cancer: A single center study
Authors: Ulivi Paola , Capelli Laura , Valgiusti Martina , Zoli Wainer , Scarpi Emanuela , Chiadini Elisa , Rosetti Paola , Bravaccini Sara , Calistri Daniele , Saragoni Luca , Casadei Gardini Andrea , Ragazzini Angela , Frassineti Giovanni Luca , Amadori Dino , Passardi Alessandro
Published: May 2012

Background

KRASmutations negatively affect outcome after treatment with cetuximab in metastatic colorectal cancer (mCRC) patients. As only 20% ofKRASwild type (WT) patients respond to cetuximab it is possible that other mutations, constitutively activating the EGFR pathway, are present in the non-respondingKRASWT patients. We retrospectively analyzed objective tumor response rate, (ORR) progression-free (PFS) and overall survival (OS) with respect to the mutational status ofKRAS,BRAF,PIK3CAand PTEN expression in mCRC patients treated with a cetuximab-based regimen.

Methods

67 mCRC patients were enrolled onto the study. DNA was extracted from paraffin-embedded sections derived from primary or metastatic lesions. Exon 2 ofKRASand exon 15 ofBRAFwere analyzed by direct sequencing,PIK3CAwas evaluated by pyrosequencing and PTEN expression by immunohistochemistry.

Results

BRAFandPIK3CAmutations were independently associated with worse PFS (p = 0.006 andp = 0.028, respectively) and OS (p = 0.008 andp = 0.029, respectively). No differences in clinical outcome were found between patients who were positive or negative for PTEN expression. Conversely, patients negative forKRAS,BRAFandPIK3CAmutations were characterized by significantly better ORR, PFS and OS than patients with at least one of these mutations.

Conclusions

BRAFandPIK3CAmutations would seem to be independent predictors of anti-EGFR therapy effectiveness and could be taken into consideration during treatment decision making.
Common fixed point and approximation results for generalized (f, g)-weak contractions
Authors: Akbar Farhana , Khan Abdul Rahim , Sultana Nazra
Published: May 2012

The existence of common fixed points is established for three mappings whereTis generalized (f,g)-weakly contractive mapping on a nonempty subset of a Banach space. As applications, the invariant approximation results are proved. Our results unify and improve several recent results in the literature.

Mathematics Subject Classification 2000:Primary, 47H10; 54H25; 47E10.
Remarks on some recent fixed point theorems
Authors: Aydi Hassen , Karapınar Erdal , Samet Bessem
Published: May 2012

The purpose of this article is to show that some recent fixed point theorems are particular results of previous existing theorems in the literature.

Mathematics Subject Classification 2000: 54H25; 47H10.
Histamine modulates microglia function
Authors: Ferreira Raquel , Santos Tiago , Gonçalves Joana , Baltazar Graça , Ferreira Lino , Agasse Fabienne , Bernardino Liliana
Published: May 2012

Background

Histamine is commonly acknowledged as an inflammatory mediator in peripheral tissues, leaving its role in brain immune responses scarcely studied. Therefore, our aim was to uncover the cellular and molecular mechanisms elicited by this molecule and its receptors in microglia-induced inflammation by evaluating cell migration and inflammatory mediator release.

Methods

Firstly, we detected the expression of all known histamine receptor subtypes (H1R, H2R, H3R and H4R), using a murine microglial cell line and primary microglia cell cultures from rat cortex, by real-time PCR analysis, immunocytochemistry and Western blotting. Then, we evaluated the role of histamine in microglial cell motility by performing scratch wound assays. Results were further confirmed using murine cortex explants. Finally, interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels were evaluated by ELISA measurements to determine the role of histamine on the release of these inflammatory mediators.

Results

After 12 h of treatment, 100 μM histamine and 10 μg/ml histamine-loaded poly (lactic-co-glycolic acid) microparticles significantly stimulated microglia motility via H4R activation. In addition, migration involves α5β1 integrins, and p38 and Akt signaling pathways. Migration of microglial cells was also enhanced in the presence of lipopolysaccharide (LPS, 100 ng/ml), used as a positive control. Importantly, histamine inhibited LPS-stimulated migration via H4R activation. Histamine or H4R agonist also inhibited LPS-induced IL-1β release in both N9 microglia cell line and hippocampal organotypic slice cultures.

Conclusions

To our knowledge, we are the first to show a dual role of histamine in the modulation of microglial inflammatory responses. Altogether, our data suggest that histamine per se triggers microglia motility, whereas histamine impedes LPS-induced microglia migration and IL-1β release. This last datum assigns a new putative anti-inflammatory role for histamine, acting via H4R to restrain exacerbated microglial responses under inflammatory challenge, which could have strong repercussions in the treatment of CNS disorders accompanied by microglia-derived inflammation.
Molecular characterization of Umbre virus (Bunyaviridae)
Authors: Yadav Pragya D , Mishra Akhilesh C , Mourya Devendra T
Published: May 2012

Umbre (UMB) virus was first isolated from India in 1955 and classified as Orthobunyavirus (Turlock serogroup). Eight isolates of this virus, isolated from Culex mosquitoes were characterized on the basis of partial glycoprotein (G2) gene. Twenty-six percent differences at nucleotide level while 17% differences at amino acid level were noted within different isolates. Phylogentic data shows that this virus represents a distinct group within the genus Orthobunyavirus.
Respiratory syncytial virus (RSV) attachment and nonstructural proteins modify the type I interferon response associated with suppressor of cytokine signaling (SOCS) proteins and IFN-stimulated gene-15 (ISG15)
Authors: Moore Elizabeth C , Barber Jamie , Tripp Ralph A
Published: May 2012

Respiratory syncytial virus (RSV) is a major cause of severe lower airway disease in infants and young children, but no safe and effective RSV vaccine is yet available. Factors attributing to this problem are associated with an incomplete understanding of the mechanisms by which RSV modulates the host cell response to infection. In the present study, we investigate suppressor of cytokine signaling (SOCS)-1 and SOCS3 expression associated with the type I IFN and IFN-stimulated gene (ISG)-15 response following infection of mouse lung epithelial (MLE-15) cells with RSV or RSV mutant viruses lacking the G gene, or NS1 and NS2 gene deletions. Studies in MLE-15 cells are important as this cell line represents the distal bronchiolar and alveolar epithelium of mice, the most common animal model used to evaluate the host cell response to RSV infection, and exhibit morphologic characteristics of alveolar type II cells, a primary cell type targeted during RSV infection. These results show an important role for SOCS1 regulation of the antiviral host response to RSV infection, and demonstrate a novel role for RSV G protein manipulation of SOCS3 and modulation of ISG15 and IFNβ mRNA expression.
Developing effective chronic disease interventions in Africa: insights from Ghana and Cameroon
Authors: de-Graft Aikins Ama , Boynton Petra , Atanga Lem L
Published: May 2012

Background

Africa faces an urgent but 'neglected epidemic' of chronic disease. In some countries stroke, hypertension, diabetes and cancers cause a greater number of adult medical admissions and deaths compared to communicable diseases such as HIV/AIDS or tuberculosis. Experts propose a three-pronged solution consisting of epidemiological surveillance, primary prevention and secondary prevention. In addition, interventions must be implemented through 'multifaceted multi-institutional' strategies that make efficient use of limited economic and human resources. Epidemiological surveillance has been prioritised over primary and secondary prevention. We discuss the challenge of developing effective primary and secondary prevention to tackle Africa's chronic disease epidemic through in-depth case studies of Ghanaian and Cameroonian responses.

Methods

A review of chronic disease research, interventions and policy in Ghana and Cameroon instructed by an applied psychology conceptual framework. Data included published research and grey literature, health policy initiatives and reports, and available information on lay community responses to chronic diseases.

Results

There are fundamental differences between Ghana and Cameroon in terms of 'multi-institutional and multi-faceted responses' to chronic diseases. Ghana does not have a chronic disease policy but has a national health insurance policy that covers drug treatment of some chronic diseases, a culture of patient advocacy for a broad range of chronic conditions and mass media involvement in chronic disease education. Cameroon has a policy on diabetes and hypertension, has established diabetes clinics across the country and provided training to health workers to improve treatment and education, but lacks community and media engagement. In both countries churches provide public education on major chronic diseases. Neither country has conducted systematic evaluation of the impact of interventions on health outcomes and cost-effectiveness.

Conclusions

Both Ghana and Cameroon require a comprehensive and integrative approach to chronic disease intervention that combines structural, community and individual strategies. We outline research and practice gaps and best practice models within and outside Africa that can instruct the development of future interventions.
Association of umbilical cord blood lead with neonatal behavior at varying levels of exposure
Authors: Patel Archana B , Mamtani Manju R , Thakre Tushar P , Kulkarni Hemant
Published: May 2012

Background

In the light of the ongoing debate about lowering the cut-off for acceptable blood lead level to <5 μg/dL from the currently recommended level of <10 μg/dL, we considered whether prenatal exposure to varying levels of lead is associated with similar or disparate effects on neonatal behavior.

Methods

Using Brazelton's Neonatal Behavioral Assessment Scale (NBAS), an epidemiological approach and robust statistical techniques like multivariate linear regression, logistic regression, Poisson regression and structural equations modeling analyses we estimated the simultaneous indirect effects of umbilical cord blood lead (CBL) levels and other neonatal covariates on the NBAS clusters.

Results

We observed that when analyzed in all study subjects, the CBL levels independently and strongly influenced autonomic stability and abnormal reflexes clusters. However, when the analysis was restricted to neonates with CBL <10 μg/dL, CBL levels strongly influenced the range of state, motor and autonomic stability clusters. Abnormal walking reflex was consistently associated with an increased CBL level irrespective of the cut-off for CBL, however, only at the lower cut-offs were the predominantly behavioral effects of CBL discernible.

Conclusion

Our results further endorse the need to be cognizant of the detrimental effects of blood lead on neonates even at a low-dose prenatal exposure.
Primary central nervous system plasmablastic lymphoma presenting in human immunodeficiency virus-negative but Epstein-Barr virus-positive patient: A case report
Authors: Zhang Li Ying , Lin Hui Yun , Gao Lan Xiang , Li Lin , Tian Yu Wang , Liu Zhi Qin , Shi Xiao Hua , Liang Zhi Yong
Published: May 2012

We report a 32-year-old Outer Mongolian man, with plasmablastic lymphoma (PBL) primarily occured in the central nervous system and diagnosed by surgical resection. This patient appeared headache and Magnetic resonance imaging (MRI) showed multiple lesions in the right cerebral hemisphere including the right frontal-parietal lobe and right basal ganglia and the left cerebellum, he was diagnosed as lymphoma by stereotactic biopsy in January 2009 in local hospital, and was given radiotherapy 33 times after the biopsy. The patient was admitted to The Military General Hospital of Beijing PLA., Beijing, P.R. China on March 9th, 2011, with chief complaints of right limbs convulsioned suddenly, then fell down and lose of his consciousness, then awoke after 4 to 5 minutes, with symptoms of angulus oris numbness and the right upper limb powerless ten days ago.

MRI of the brain revealed a well-defined hyperdense and enhancing mass in the left frontal-parietal lobe, the meninges are closely related, there was extensive peritumoural edema noted with pressure effects, as evident by effacement of the left lateral ventricles and a 0.5 cm shift of the midline to the right side.

Surgical resection showed markedly atypical, large singly dispersed or cohesive proliferation of plasmacytoid cells with frequent abnormal mitoses and binucleation, some neoplastic cells were large with round or oval nuclei and showed coarse chromatin and smaller or unapparent nucleoli, some neoplastic cells with prominent nucleoli, apoptosis and necrosis were often presented. Immunohistochemistry staining and gene rearrangement together with other supportive investigation confirmed the diagnosis of primary central nervous system plasmablastic lymphoma. A month later, he was started on chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, leurocristime and prednisone) for a week. Other supportive treatment was provided for symptomatic epilepsy. The patient regained muscle strength in both upper limbs and right lower limb and the symptomatic epilepsy was controlled after two weeks. Then the patient was discharged. Follow-up data shows the patient to be alive eleven months after discharge.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1649317674697046.
Near infrared spectroscopy (NIRS) of the thenar eminence in anesthesia and intensive care
Authors: Lipcsey Miklos , Woinarski Nicholas CZ , Bellomo Rinaldo
Published: May 2012

Near infrared spectroscopy of the thenar eminence (NIRSth) is a noninvasive bedside method for assessing tissue oxygenation. The NIRS probe emits light with several wavelengths in the 700- to 850-nm interval and measures the reflected light mainly from a predefined depth. Complex physical models then allow the measurement of the relative concentrations of oxy and deoxyhemoglobin, and thus tissue saturation (StO2), as well as an approximation of the tissue hemoglobin, given as tissue hemoglobin index.

Here we review of current knowledge of the application of NIRSthin anesthesia and intensive care.

We performed an analytical and descriptive review of the literature using the terms “near-infrared spectroscopy” combined with “anesthesia,” “anesthesiology,” “intensive care,” “critical care,” “sepsis,” “bleeding,” “hemorrhage,” “surgery,” and “trauma” with particular focus on all NIRS studies involving measurement at the thenar eminence.

We found that NIRSthhas been applied as clinical research tool to perform both static and dynamic assessment of StO2. Specifically, a vascular occlusion test (VOT) with a pressure cuff can be used to provide a dynamic assessment of the tissue oxygenation response to ischemia. StO2changes during such induced ischemia-reperfusion yield information on oxygen consumption and microvasculatory reactivity. Some evidence suggests that StO2during VOT can detect fluid responsiveness during surgery. In hypovolemic shock, StO2can help to predict outcome, but not in septic shock. In contrast, NIRS parameters during VOT increase the diagnostic and prognostic accuracy in both hypovolemic and septic shock. Minimal data are available on static or dynamic StO2used to guide therapy.

Although the available data are promising, further studies are necessary before NIRSthcan become part of routine clinical practice.
Crk adaptor proteins act as key signaling integrators for breast tumorigenesis
Authors: Fathers Kelly E , Bell Emily S , Rajadurai Charles V , Cory Sean , Zhao Hong , Mourskaia Anna , Zuo Dongmei , Madore Jason , Monast Anie , Mes-Masson Anne-Marie , Grosset Andree-Anne , Gaboury Louis , Hallet Michael , Siegel Peter , Park Morag
Published: May 2012

Introduction

CT10 regulator of kinase (Crk) adaptor proteins (CrkI, CrkII and CrkL) play a role in integrating signals for migration and invasion of highly malignant breast cancer cell lines. This has important implications, as elevated CrkI/II protein levels were observed in a small cohort of breast cancer patients, which identified a potential role for Crk proteins in breast cancer progression. Numerous in vitro studies identified a role for Crk proteins in cell motility, but little is known about how Crk proteins contribute to breast cancer progression in vivo.

Methods

The clinical significance of Crk proteins in human breast cancer was assessed by analyzing published breast cancer datasets using a gene expression signature that was generated following CrkII over-expression and by examining Crk protein expression in tissue microarrays of breast tumors (n = 254). Stable knockdown of Crk (CrkI/CrkII/CrkL) proteins was accomplished using a short hairpin RNA (shRNA)-mediated approach in two basal breast cancer cell lines, MDA-231 1833TR and SUM1315, where the former have a high affinity to form bone metastases. Both in vitro assays (cell migration, invasion, soft agar growth) and in vivo experiments (intra-cardiac, tibial and mammary fat pad injections) were performed to assess the functional significance of Crk proteins in breast cancer.

Results

A gene signature derived following CrkII over-expression correlated significantly with basal breast cancers and with high grade and poor outcome in general. Moreover, elevated Crk immunostaining on tissue microarrays revealed a significant association with highly proliferative tumors within the basal subtype. RNAi-mediated knockdown of all three Crk proteins in metastatic basal breast cancer cells established a continued requirement for Crk in cell migration and invasion in vitro and metastatic growth in vivo. Furthermore, Crk ablation suppressed anchorage independent growth and in vivo orthotopic tumor growth. This was associated with diminished cell proliferation and was rescued by expression of non-shRNA targeted CrkI/II. Perturbations in tumor progression correlated with altered integrin signaling, including decreased cell spreading, diminished p130Cas phosphorylation, and Cdc42 activation.

Conclusions

These data highlight the physiological importance of Crk proteins in regulating growth of aggressive basal breast cancer cells and identify Crk-dependent signaling networks as promising therapeutic targets.
Metformin overdose, but not lactic acidosis per se, inhibits oxygen consumption in pigs
Authors: Protti Alessandro , Fortunato Francesco , Monti Massimo , Vecchio Sarah , Gatti Stefano , Comi Giacomo P , Giuseppe Rachele De , Gattinoni Luciano
Published: May 2012

Introduction

Hepatic mitochondrial dysfunction may play a critical role in the pathogenesis of metformin-induced lactic acidosis. However, patients with severe metformin intoxication may have a 30 to 60% decrease in their global oxygen consumption, as for generalized inhibition of mitochondrial respiration. We developed a pig model of severe metformin intoxication to validate this clinical finding and assess mitochondrial function in liver and other tissues.

Methods

Twenty healthy pigs were sedated and mechanically ventilated. Ten were infused with a large dose of metformin (4 to 8 g) and five were not (sham controls). Five others were infused with lactic acid to clarify whether lactic acidosis per se diminishes global oxygen use. Arterial pH, lactatemia, global oxygen consumption (VO2) (metabolic module) and delivery (DO2) (cardiac output by thermodilution) were monitored for nine hours. Oxygen extraction was computed as VO2/DO2. Activities of the main components of the mitochondrial respiratory chain (complex I, II and III, and IV) were measured with spectrophotometry (and expressed relative to citrate synthase activity) in heart, kidney, liver, skeletal muscle and platelets taken at the end of the study.

Results

Pigs infused with metformin (6 ± 2 g; final serum drug level 77 ± 45 mg/L) progressively developed lactic acidosis (final arterial pH 6.93 ± 0.24 and lactate 18 ± 7 mmol/L, P < 0.001 for both). Their VO2 declined over time (from 115 ± 34 to 71 ± 30 ml/min, P < 0.001) despite grossly preserved DO2 (from 269 ± 68 to 239 ± 51 ml/min, P = 0.58). Oxygen extraction accordingly fell from 43 ± 10 to 30 ± 10% (P = 0.008). None of these changes occurred in either sham controls or pigs infused with lactic acid (final arterial pH 6.86 ± 0.16 and lactate 22 ± 3 mmol/L). Metformin intoxication was associated with inhibition of complex I in the liver (P < 0.001), heart (P < 0.001), kidney (P = 0.003), skeletal muscle (P = 0.012) and platelets (P = 0.053). The activity of complex II and III diminished in the liver (P < 0.001), heart (P < 0.001) and kidney (P < 0.005) while that of complex IV declined in the heart (P < 0.001).

Conclusions

Metformin intoxication induces lactic acidosis, inhibits global oxygen consumption and causes mitochondrial dysfunction in liver and other tissues. Lactic acidosis per se does not decrease whole-body respiration.
Higher vs. lower fluid volume for septic shock: clinical characteristics and outcome in unselected patients in a prospective, multicenter cohort
Authors: Smith Søren H , Perner Anders
Published: May 2012

Introduction

Patients with septic shock require fluid, but the optimum amount is unknown. Therefore we assessed patient characteristics and outcome associated with fluid volume in unselected patients with septic shock including those with three days of shock.

Methods

We conducted a prospective, multicenter, observational study of all adult patients with septic shock during a 3-month study period at six general ICUs: three in university hospitals and three in regional hospitals. After day 1 and 3 of shock, patients were divided into two groups according to the overall median fluid volumes. Characteristics between these groups were compared using non-parametric and Chi-square statistics.

Results

The 164 included patients received median 4.0 l (IQR 2.3-6.3) of fluid during the first day of septic shock. Patients receiving higher volumes (> 4.0 l) on day 1 had higher p-lactate (3.4 (2.2-5.5) vs. 2.0 (1.6-3.0) mmol l-1, P < 0.0001) compared to those receiving lower volumes. In contrast simplified acute physiology score (SAPS) II (54 (45-64) vs. 54 (45-67), P = 0.73), sequential organ failure assessment (SOFA) score (11 (9-13) vs. 11 (9-13), P = 0.78) and 90-day mortality (48 vs. 53%, P = 0.27) did not differ between groups. The 95 patients who still had shock on day 3 had received 7.5 l (4.3 - 10.8) of fluid by the end of day 3. Patients receiving higher volumes (> 7.5 l) had higher p-lactate (2.6 (1.7-3.4) vs. 1.9 (1.6-2.4) mmol l-1, P < 0.01) on day 3 and lower 90-day mortality (40 vs. 62%, P = 0.03) than those receiving lower volumes in spite of comparable admission SAPS II (53 (46-67) vs. 55 (49-62), P = 0.47) and SOFA scores on day 3 (10 (8-13) vs. 11 (10-14), P = 0.33).

Conclusions

In this cohort of unselected ICU patients with septic shock, initial fluid volume was not associated with mortality. In patients with shock for three days or more, higher fluid volumes including crystalloids, colloids and blood products were associated with reduced mortality.
Prospective Study of Health-Related Quality of Life for Children With Brain Tumors Treated With Proton Radiotherapy
Authors: Kuhlthau Karen A. , Pulsifer Margaret B. , Yeap Beow Y. , Rivera Morales Dianali , Delahaye Jennifer , Hill Kristen S. , Ebb David , Abrams Annah N. , MacDonald Shannon M. , Tarbell Nancy J. , Yock Torunn I.
Published: May 2012

Purpose

We describe the health-related quality of life (HRQoL) of a cohort of children with brain tumors treated with proton radiotherapy.

Patients and Methods

We recruited 142 pediatric patients with brain tumors (age 2 to 18 years) and parents of such patients treated with proton radiation at Massachusetts General Hospital from 2004 to 2010. HRQoL was assessed using the PedsQL core, brain tumor, and cancer modules (range, 0 to 100). Assessments took place during radiation and annually thereafter. We examined correlations of HRQoL with disease, treatment, and cognitive and behavioral data.

Results

Overall reports of HRQoL during treatment were 74.8 and 78.1 for child self-report (CSR) and 67.0 and 74.8 for parent proxy report (PPR) for the core and brain tumor modules, respectively. PPR demonstrated lower HRQoL scores than CSR, but the two were highly correlated. Higher HRQoL scores were significantly associated with Wechsler Full Scale Intelligence Quotient scores (administered via the age-appropriate version) and better scores on two behavioral measures. Disease type also correlated with PPR core total HRQoL score at the beginning of treatment: medulloblastoma or primitive neuroectodermal tumors, 57.8; germ cell tumors, 63.5; ependymoma or high-grade glioma, 69.8; low-grade glioma, 71.5; and other low-grade neoplasms, 78.0 (P = .001). Craniospinal irradiation and chemotherapy were negatively correlated with HRQoL.

Conclusion

This is the first study to our knowledge of HRQoL in a cohort of children with brain tumors treated with proton radiation. This prospective study demonstrates the effect of disease type and intensity of treatment on HRQoL. It further suggests that where CSR is not possible, PPR is appropriate in most circumstances.
Tobacco Smoking and Increased Risk of Death and Progression for Patients With p16-Positive and p16-Negative Oropharyngeal Cancer
Authors: Gillison Maura L. , Zhang Qiang , Jordan Richard , Xiao Weihong , Westra William H. , Trotti Andy , Spencer Sharon , Harris Jonathan , Chung Christine H. , Ang K. Kian
Published: May 2012

Purpose

Tobacco smoking is associated with oropharynx cancer survival, but to what extent cancer progression or death increases with increasing tobacco exposure is unknown.

Patients and Methods

Patients with oropharynx cancer enrolled onto a phase III trial of radiotherapy from 1991 to 1997 (Radiation Therapy Oncology Group [RTOG] 9003) or of chemoradiotherapy from 2002 to 2005 (RTOG 0129) were evaluated for tumor human papillomavirus status by a surrogate, p16 immunohistochemistry, and for tobacco exposure by a standardized questionnaire. Associations between tobacco exposure and overall survival (OS) and progression-free survival (PFS) were estimated by Cox proportional hazards models.

Results

Prevalence of p16-positive cancer was 39.5% among patients in RTOG 9003 and 68.0% in RTOG 0129. Median pack-years of tobacco smoking were lower among p16-positive than p16-negative patients in both trials (RTOG 9003: 29 v 45.9 pack-years; P = .02; RTOG 0129: 10 v 40 pack-years; P < .001). After adjustment for p16 and other factors, risk of progression (PFS) or death (OS) increased by 1% per pack-year (for both, hazard ratio [HR], 1.01; 95% CI, 1.00 to 1.01; P = .002) or 2% per year of smoking (for both, HR, 1.02; 95% CI, 1.01 to 1.03; P < .001) in both trials. In RTOG 9003, risk of death doubled (HR, 2.19; 95% CI, 1.46 to 3.28) among those who smoked during radiotherapy after accounting for pack-years and other factors, and risk of second primary tumors increased by 1.5% per pack-year (HR, 1.015; 95% CI, 1.005 to 1.026).

Conclusion

Risk of oropharyngeal cancer progression and death increases directly as a function of tobacco exposure at diagnosis and during therapy and is independent of tumor p16 status and treatment.