bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fiberoptic Resonance Raman Spectroscopy to Measure Carotenoid Oxidative Breakdown in Live Tissues
Authors: Bentz Brandon G. , Diaz Jason , Ring Terry A. , Wade Mark , Kennington Konrad , Burnett David M. , McClane Robert , Fitzpatrick Frank A. 
Published: March 2010

Abstract
Based on compelling epidemiologic and corroboratory in vitro studies, carotenoids are thought to have great potential as dietary prevention against cancer. Yet, carotenoid-based chemopreventive trials have found very contradictory results. Definitive conclusions from these trials are hampered by an inability to accurately and safely measure carotenoids in specific tissues at risk of cancer development. Raman spectroscopy has been proposed as an optical technology with which to analyze various molecules in live tissues. One major obstacle that impedes the clinical use of this powerful technology is the lack of a fiberoptic Raman probe suitable for endoscopic tissue evaluation. A single-fiber resonance Raman Spectroscope capable of noninvasive “optical biopsies” to measure carotenoid concentrations in live tissues has been developed. The accuracy of this Raman instrument was confirmed by comparison with more standard methods of spectrophotometry and high-pressure liquid chromatography using solubilized β-carotene (BC) and BC-loaded cells before use in a small patient cohort. This Raman instrument detected intact BC as well as BC oxidative breakdown as a decrement of its Raman signal in cells. Use of the Raman instrument in our small cohort study showed its feasibility for measuring human tissues and raised some potentially intriguing possibilities about BC tissue pharmacokinetics and oxidative biology. Based on these results, our newly developed single fiberoptic resonance Raman instrument may provide a very useful method of measuring carotenoids and their oxidative breakdown within live tissue during future carotenoid chemopreventive trials. This proof-of-concept study provides the foundation to justify future validation of our Raman prototype. Cancer Prev Res; 3(4); 529–38. ©2010 AACR.
Knockout of the Tumor Suppressor Gene Gprc5a in Mice Leads to NF-κB Activation in Airway Epithelium and Promotes Lung Inflammation and Tumorigenesis
Authors: Deng Jiong , Fujimoto Junya , Ye Xiao-Feng , Men Tao-Yan , Van Pelt Carolyn S. , Chen Yu-Long , Lin Xiao-Feng , Kadara Humam , Tao Qingguo , Lotan Dafna , Lotan Reuben 
Published: March 2010

Abstract
Mouse models can be useful for increasing the understanding of lung tumorigenesis and assessing the potential of chemopreventive agents. We explored the role of inflammation in lung tumor development in mice with knockout of the tumor suppressor Gprc5a. Examination of normal lung tissue and tumors from 51 Gprc5a+/+ (adenoma incidence, 9.8%; adenocarcinoma, 0%) and 38 Gprc5a−/− mice (adenoma, 63%; adenocarcinoma, 21%) revealed macrophage infiltration into lungs of 45% of the Gprc5a−/− mice and 8% of Gprc5a+/+ mice and the direct association of macrophages with 42% of adenomas and 88% of adenocarcinomas in the knockout mice. Gprc5a−/− mouse lungs contained higher constitutive levels of proinflammatory cytokines and chemokines and were more sensitive than lungs of Gprc5a+/+ mice to stimulation of NF-κB activation by lipopolysaccharide in vivo. Studies with epithelial cells cultured from tracheas of Gprc5a−/− and Gprc5a+/+ mice revealed that Gprc5a loss is associated with increased cell proliferation, resistance to cell death in suspension, and increased basal, tumor necrosis factor α–induced, and lipopolysaccharide-induced NF-κB activation, which were reversed partially in Gprc5a−/− adenocarcinoma cells by reexpression of Gprc5a. Compared with Gprc5a+/+ cells, the Gprc5a−/− cells produced higher levels of chemokines and cytokines and their conditioned medium induced more extensive macrophage migration. Silencing Gprc5a and the p65 subunit of NF-κB in Gprc5a+/+ and Gprc5a−/− cells, respectively, reversed these effects. Thus, Gprc5a loss enhances NF-κB activation in lung epithelial cells, leading to increased autocrine and paracrine interactions, cell autonomy, and enhanced inflammation, which may synergize in the creation of a tumor-promoting microenvironment. Cancer Prev Res; 3(4); 424–37. ©2010 AACR.
Correlates of Self-Stigma Among Outpatients With Mental Illness in Lagos, Nigeria
Authors: Adewuya Abiodun O. , Owoeye Adekile O. , Erinfolami A.O. , Ola Bolanle A. 
Published: March 2010

Background: Studies in this region have all been limited to public stigma whereas little is known about the extent of self-stigma. Aims: To assess the extent, domains and correlates of self-stigma among psychiatric outpatients in Lagos, Nigeria. Method: Psychiatric outpatients ( n = 342) from three centres completed a modified version of the Internalized Stigma of Mental Illness scale (ISMI) as a measure of their self-stigma. They were also evaluated for various sociodemographic and clinical related variables. Results: A total of 74 ( n = 21.6%) patients were classified as having ‘high selfstigma’. The correlates of high self-stigma included unemployment (OR 3.85, 95% CI 2.55—7.00), poor social support (OR 10.82, 95% CI 4.85—24.84), longer duration of illness (OR 10.35, 95% CI 4.36—25.78) and having full insight into the illness (OR 4.23, 95% CI 2.16—8.76). Conclusions: Self-stigma is a common phenomenon in psychiatric outpatients in this environment. The present anti-stigma programmes must extend to regions of sub-Saharan Africa and incorporate self-stigma as a matter of priority.
Relative contribution of motor impairments to limitations in activity and restrictions in participation in adults with hemiplegic cerebral palsy
Authors: Chiu Hsiu-Ching , Ada Louise , Butler Jane , Coulson Susan 
Published: March 2010

Objective: To determine which motor impairments make a significant relative contribution to upper limb activity limitations, and whether activity limitations are related to participation restrictions in people with hemiplegic cerebral palsy. Design: An observational study. Setting: Neurological Rehabilitation Research Group at Faculty of Health Sciences, The University of Sydney. Subjects: Twenty-three people with hemiplegic cerebral palsy participated. Main measures: Four motor impairments (strength, coordination, spasticity and contracture), upper limb activity and participation were measured. Multiple regression was used to determine the relative contribution of motor impairments to activity limitations. Linear regression was used to determine the correlation between activity and participation. Results: The four motor impairments accounted for 63% of the variance in upper limb activity with coordination independently accounting for 21% (P<0.01). Upper limb activity accounted for 13% of the variance in participation (P=0.10). Conclusions: The findings imply that coordination of four motor impairments makes the largest independent relative contribution to activity limitations, whereas upper limb activity makes less contribution to participation in people with mild and moderate hemiplegic cerebral palsy.
An exploration of personal initiative theory in the role of consultant nurses
Authors: Redfern Sally , Coster Samantha , Evans Amanda , Dewe Philip 
Published: March 2010

The aim in this paper is to investigate the contribution personal initiative theory makes in understanding the consultant nurse role. The role was introduced in the UK in 2000 to improve patient outcomes, clinical leadership and retention of experienced clinicians. A larger study used a multi-method approach to collect quantitative and qualitative data from focus groups, interviews and a questionnaire administered nationally at two time points. Findings from longitudinal telephone interviews with 30 consultant nurses are the focus of this paper. Three consultant nurses were selected as case studies to examine the potential of personal initiative theory when applied to new nursing roles. The activities of two of the three demonstrated a high level of personal initiative in the job. They persisted in overcoming problems faced in improving practice. The third scored lower: she emerged as a reactive conformist and less likely than the other two to pursue initiatives of her own. Personal initiative theory has potential as a framework for evaluating the consultant nurse role, although further research is needed to test it. The longitudinal analysis revealed a determination to stay in the job and overcome difficult challenges when consultants show initiative and are making progress in achieving change.
A congenital activating mutant of WASp causes altered plasma membrane topography and adhesion under flow in lymphocytes
Authors: Burns Siobhan O. , Killock David J. , Moulding Dale A. , Metelo Joao , Nunes Joao , Taylor Ruth R. , Forge Andrew , Thrasher Adrian J. , Ivetic Aleksandar 
Published: March 2010

AbstractLeukocytes rely on dynamic actin-dependent changes in cell shape to pass through blood vessels, which is fundamental to immune surveillance. Wiskott-Aldrich Syndrome protein (WASp) is a hematopoietic cell–restricted cytoskeletal regulator important for modulating cell shape through Arp2/3-mediated actin polymerization. A recently identified WASpI294T mutation was shown to render WASp constitutively active in vivo, causing increased filamentous (F)–actin polymerization, high podosome turnover in macrophages, and myelodysplasia. The aim of this study was to determine the effect of WASpI294T expression in lymphocytes. Here, we report that lymphocytes isolated from a patient with WASpI294T, and in a cellular model of WASpI294T, displayed abnormal microvillar architecture, associated with an increase in total cellular F-actin. Microvillus function was additionally altered as lymphocytes bearing the WASpI294T mutation failed to roll normally on L-selectin ligand under flow. This was not because of defects in L-selectin expression, shedding, cytoskeletal anchorage, or membranal positioning; however, under static conditions of adhesion, WASpI294T-expressing lymphocytes exhibited altered dynamic interaction with L-selectin ligand, with a significantly reduced rate of adhesion turnover. Together, our results demonstrate that WASpI294T significantly affects lymphocyte membrane topography and L-selectin–dependent adhesion, which may be linked to defective hematopoiesis and leukocyte function in affected patients.
Two mutations in the KINDLIN3 gene of a new leukocyte adhesion deficiency III patient reveal distinct effects on leukocyte function in vitro
Authors: McDowall Alison , Svensson Lena , Stanley Paula , Patzak Irene , Chakravarty Probir , Howarth Kimberley , Sabnis Himalee , Briones Michael , Hogg Nancy 
Published: March 2010

AbstractIn the disorder leukocyte adhesion deficiency III (LAD-III), integrins on platelets and leukocytes are expressed but fail to function and this leads to severe bleeding and infections at an early age. Mutation in the KINDLIN3 (FERMT3) gene is the cause of LAD-III in patients from the Middle East, Malta, and Turkey. We describe 2 novel homozygous mutations in the KINDLIN3 gene of a new African-American patient that destabilize KINDLIN3 mRNA leading to loss of kindlin-3 protein. Transfection of wild-type (WT) KINDLIN3 cDNA restored integrin-related adhesion and migration in the LAD-III patient's T and B lymphocytes. We analyzed the individual mutations separately in vitro to learn more about the function of the kindlin-3 protein. The first G>A mutation gives rise to a Gly308Arg change at the end of FERM (protein 4.1, ezrin, radixin, moesin) subdomain 2, and the second mutation is a base deletion causing early termination within the pleckstrin homology (PH) domain. This second mutation prevented membrane association of kindlin-3 and did not restore either adhesion or migration, whereas the FERM subdomain 2 mutation affected only migration. Thus, these LAD-III patient mutations have highlighted functionally important regions of kindlin-3 that alter leukocyte integrin-dependent function in 2 distinct ways.
Toll-like receptor–induced reactivity and strongly potentiated IL-8 production in granulocytes mobilized for transfusion purposes
Authors: Drewniak Agata , Tool Anton T. J. , Geissler Judy , van Bruggen Robin , van den Berg Timo K. , Kuijpers Taco W. 
Published: March 2010

AbstractTransfusion of granulocytes from granulocyte-colony stimulating factor (G-CSF)/dexamethasone (dexa)–treated donors can be beneficial for neutropenic recipients that are refractory to antimicrobial therapy. G-CSF/dexa treatment not only increases the number of circulating neutrophils but also affects their gene expression. Because of the intended transfusion of these granulocytes into patients who are severely ill, it is of importance to establish to what extent mobilization affects the cellular behavior of neutrophils. Here, we studied the effects of mobilization on Toll-like receptor (TLR)–mediated responses. Mobilized granulocytes displayed increased gene and protein expression of TLR2, TLR4, TLR5, and TLR8. Although mobilized granulocytes displayed normal priming of nicotinamide adenine dinucleotide phosphate oxidase activity and a slight increase in adhesion in response to TLR stimulation, these cells produced massive amounts of interleukin-8 (IL-8), in particular to TLR2 and TLR8 stimulation. The increase in IL-8 release occurred despite reduced IL-8 mRNA levels in the donor granulocytes after in vivo G-CSF/dexa treatment, indicating that the enhanced TLR-induced IL-8 production was largely determined by posttranscriptional regulation. In summary, granulocytes mobilized for transfusion purposes show enhanced TLR responsiveness in cytokine production, which is anticipated to be beneficial for the function of these cells on transfusion into patients.
Molecular mechanisms involving sigma receptor–mediated induction of MCP-1: implication for increased monocyte transmigration
Authors: Yao Honghong , Yang Yanjing , Kim Kee Jun , Bethel-Brown Crystal , Gong Nan , Funa Keiko , Gendelman Howard E. , Su Tsung-Ping , Wang John Q. , Buch Shilpa 
Published: March 2010

AbstractCocaine abuse hastens the neurodegeneration often associated with advanced HIV-1 infection. The mechanisms, in part, revolve around the neuroinflammatory processes mediated by the chemokine monocyte chemotactic protein-1 (MCP-1/CCL2). Understanding factors that modulate MCP-1 and, in turn, facilitate monocyte extravasation in the brain is thus of paramount importance. We now demonstrate that cocaine induces MCP-1 in rodent microglia through translocation of the sigma receptor to the lipid raft microdomains of the plasma membrane. Sequential activation of Src, mitogen-activated protein kinases (MAPKs), and phosphatidylinositol-3′ kinase (PI3K)/Akt and nuclear factor κB (NF-κB) pathways resulted in increased MCP-1 expression. Furthermore, conditioned media from cocaine-exposed microglia increased monocyte transmigration, and thus was blocked by antagonists for CCR2 or sigma receptor. These findings were corroborated by demonstrating increased monocyte transmigration in mice exposed to cocaine, which was attenuated by pretreatment of mice with the sigma receptor antagonist. Interestingly, cocaine-mediated transmigratory effects were not observed in CCR2 knockout mice. We conclude that cocaine-mediated induction of MCP-1 accelerates monocyte extravasation across the endothelium. Understanding the regulation of MCP-1 expression and functional changes by cocaine/sigma receptor system may provide insights into the development of potential therapeutic targets for HIV-1–associated neurocognitive disorders.
Acute mercury poisoning: a case report
Authors: Sarikaya Sezgin , Karcioglu Ozgur , Ay Didem , Cetin Aslı , Aktas Can , Serinken Mustafa 
Published: March 2010

Abstract

Background
Mercury poisoning can occur as a result of occupational hazard or suicide attempt. This article presents a 36-year-old case admitted to emergency department (ED) due to exposure to metallic mercury.

Case Presentatıon
A 36-year-old woman presented to the ED with a three-day history of abdominal pain, diarrhea and fever. One week ago her daughter had brought mercury in the liquid form from the school. She had put it on the heating stove. One day later, her 14-month old sister baby got fever and died before admission to the hospital. Her blood pressure was 134/87 mmHg; temperature, 40.2°C; heart rate 105 bpm and regular; respiration, 18 bpm; O2 saturation, 96%. Nothing was remarkable on examination and routine laboratory tests. As serine or urinary mercury levels could not be tested in the city, symptomatic chelation treatment with N-acetyl cysteine (NAC) was instituted with regard to presumptive diagnosis and history. At the 7th day of admission she was discharged without any sequelae or complaint. At the discharge day blood was drawn and sent for mercury levels which turned out to be 30 μg/dL (normal range: 0 - 10 μg/dL).

Conclusion
Public education on poisoning and the potential hazards of mercury are of vital importance for community health.
Association analysis of ADPRT1, AKR1B1, RAGE, GFPT2 and PAI-1 gene polymorphisms with chronic renal insufficiency among Asian Indians with type-2 diabetes
Authors: Prasad Pushplata , Tiwari Arun K , Kumar KM Prasanna , Ammini AC , Gupta Arvind , Gupta Rajeev , Thelma BK 
Published: March 2010

Abstract

Background
To determine association of nine single nucleotide polymorphisms (SNPs) in ADP ribosyltransferase-1 (ADPRT1), aldo-keto reductase family 1 member B1 (AKR1B1), receptor for advanced glycation end-products (RAGE), glutamine:fructose-6-phosphate amidotransferase-2 (GFPT2), and plasminogen activator inhibitor-1 (PAI-1) genes with chronic renal insufficiency (CRI) among Asian Indians with type 2 diabetes; and to identify epistatic interactionss between genes from the present study and those from renin-angiotensin-aldosterone system (RAAS), and chemokine-cytokine, dopaminergic and oxidative stress pathways (previously investigated using the same sample set).

Methods
Type 2 diabetes subjects with CRI (serum creatinine ≥3.0 mg/dl) constituted the cases (n = 196), and ethnicity and age matched individuals with diabetes for a duration of ≥ 10 years, normal renal functions and normoalbuminuria recruited as controls (n = 225). Allelic and genotypic constitution of 10 polymorphisms (SNPs) from five genes namely- ADPRT1, AKR1B1, RAGE, GFPT2 and PAI-1 with diabetic CRI was investigated. The genetic associations were evaluated by computation of odds ratio and 95% confidence interval. Multiple logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study epistatic interactions between SNPs in different genes.

Results
Single nucleotide polymorphisms -429 T>C in RAGE and rs7725 C>T SNP in 3' UTR in GFPT2 gene showed a trend towards association with diabetic CRI. Investigation using miRBase statistical tool revealed that rs7725 in GFPT2 was a perfect target for predicted miRNA (hsa miR-378) suggesting the presence of the variant 'T' allele may result in an upregulation of GFPT2 contributing to diabetic renal complication. Epistatic interaction between SNPs in transforming growth factor TGF-β1 (investigated using the same sample set and reported elsewhere) and GFPT2 genotype was observed.

Conclusions
Association of SNPs in RAGE and GFPT2 suggest that the genes involved in modulation of oxidative pathway could be major contributor to diabetic chronic renal insufficiency. In addition, GFPT2 mediated overproduction of TGF-β1 leading to endothelial expansion and thereby CRI seems likely, suggested by our observation of a significant interaction between GFPT2 with TGF-β1 genes. Further, identification of predicted miRNA targets spanning the associated SNP in GFPT2 implicates the rs7725 SNP in transcriptional regulation of the gene, and suggests GFPT2 could be a relevant target for pharmacological intervention. Larger replication studies are needed to confirm these observations.
Low HIV testing rates among tuberculosis patients in Kampala, Uganda
Authors: Sendagire Ibrahim , Schreuder Imke , Mubiru Mesach , van der Loeff Maarten Schim , Cobelens Frank , Konde-Lule Joseph 
Published: March 2010

Abstract

Background
HIV testing among tuberculosis patients is critical in improving morbidity and mortality as those found to be HIV positive will be offered a continuum of care including ART if indicated. We conducted a cross-sectional study in three Kampala City primary care clinics: to assess the level of HIV test uptake among newly diagnosed pulmonary tuberculosis (PTB) patients; to assess patient and health worker factors associated with HIV test uptake; and to determine factors associated with HIV test uptake at the primary care clinics

Methods
Adult patients who had been diagnosed with smear-positive PTB at a primary care clinic or at the referral hospital and who were being treated at any of the three clinics were interviewed. Associations between having taken the test as the main outcome and explanatory variables were assessed by multivariate logistic regression.

Results
Between April and October 2007, 112 adults were included in the study. An HIV test had been offered to 74 (66%). Of the 112 patients, 61 (82%) had accepted the test; 45 (74%) had eventually been tested; and 32 (29%) had received their test results.
Patients who were <25 yeas old, female or unemployed, or had reported no previous HIV testing, were more likely to have been tested. The strongest predictor of having been tested was if patients had been diagnosed at the referral hospital compared to the city clinic (adjusted OR 24.2; 95% CI 6.7-87.7; p < 0.001). This primarily reflected an "opt-out" (uptake 94%) versus an "opt-in" (uptake 53%) testing policy.

Conclusions
The overall HIV test uptake was surprisingly low at 40%. The HIV test uptake was significantly higher among TB patients who were identified at hospital, among females and in the unemployed.
Primary tubercular caecal perforation: a rare clinical entity
Authors: Jain Devendra K , Aggarwal Gaurav , Lubana Parvinder S , Moses Sonia , Joshi Nitin 
Published: March 2010

Abstract

Background
Intestinal tuberculosis is a common problem in endemic areas, causing considerable morbidity and mortality. An isolated primary caecal perforation of tubercular origin is exceptionally uncommon.

Case presentation
We report the case of a 39 year old male who presented with features of perforation peritonitis, which on laparotomy revealed a caecal perforation with a dusky appendix. A standard right hemicolectomy with ileostomy and peritoneal toileting was done. Histopathology revealed multiple transmural caseating granulomas with Langerhans-type giant cells and acid-fast bacilli, consistent with tuberculosis, present only in the caecum.

Conclusions
We report this extremely rare presentation of primary caecal tuberculosis to sensitize the medical fraternity to its rare occurrence, which will be of paramount importance owing to the increasing incidence of tuberculosis all over the world, especially among the developing countries.
Paraganglioma of the mediastinum: challenges in diagnosis and surgical management
Authors: Wald Ori , Shapira Oz M , Murar Aiman , Izhar Uzi 
Published: March 2010

Abstract
Mediastinal paraganglioms are rare, highly vascularized tumors arising from chromaffin tissue located in the para-aortic ganglia. Tumors tend to invade bordering structures and may also form metastasis. Up to 50% of patients are asymptomatic and diagnosis is incidental. Presenting symptoms are related to catecholamine hypersecretion or to a mass effect. Complete surgical resection remains the standard of care due to malignant potential of the tumor and poor response to chemotherapy or radiation. Strategic location of the tumor in proximity to great vessels, trachea, and recurrent laryngeal nerve poses challenge for the surgeon. We report a case of a 59-year old asymptomatic female who was incidentally diagnosed with a middle mediastinal mass on a positron-emission tomography (PET-CT) scan performed as part of breast cancer surveillance. Complete resection of the tumor was achieved using cardiopulmonary bypass. The patient recovered uneventfully and in a ten-month follow up there is no evidence of recurrence.