bluuebunny/crossref_metadata_2025 huggingface dataset:
Noninvasive determination of exercise-induced hydrodgen ion threshold through direct optical measurement
Authors: Soller Babs R. , Yang Ye , Lee Stuart M. C. , Wilson Cassie , Hagan R. Donald
Published: December 2007

The intensity of exercise above which oxygen uptake (V̇o2) does not account for all of the required energy to perform work has been associated with lactate accumulation in the blood (lactate threshold, LT) and elevated carbon dioxide output (gas exchange threshold). An increase in hydrogen ion concentration ([H+]) is approximately concurrent with elevation of blood lactate and CO2 output during exercise. Near-infrared spectra (NIRS) and invasive interstitial fluid pH (pHm) were measured in the flexor digitorum profundus during handgrip exercise to produce a mathematical model relating the two measures with an estimated error of 0.035 pH units. This NIRS pHm model was subsequently applied to spectra collected from the vastus lateralis of 10 subjects performing an incremental-intensity cycle protocol. Muscle oxygen saturation (SmO2) was also calculated from spectra. We hypothesized that a H+ threshold could be identified for these subjects and that it would be different from but correlated with the LT. Lactate, gas exchange, SmO2, and H+ thresholds were determined as a function of V̇o2 using bilinear regression. LT was significantly different from both the gas exchange threshold (Δ = 0.27 ± 0.29 l/min) and H+ threshold (Δ = 0.29 ± 0.23 l/min), but the gas exchange threshold was not significantly different from the H+ threshold (Δ = 0.00 ± 0.38 l/min). The H+ threshold was strongly correlated with LT ( R2 = 0.95) and the gas exchange threshold ( R2 = 0.85). This initial study demonstrates the feasibility of noninvasive pHm estimations, the determination of H+ threshold, and the relationship between H+ and classical metabolic thresholds during incremental exercise.
The Study of Retinal Ganglion Cell Apoptosis Induced by Different Intensities of Microwave Irradiation
Authors: Zhou Xin-Rong , Yuan Hui-Ping , Qu Wei , Ma Chun-Yang , Li Hong-Yi , Wang Ya
Published: December 2007

Purpose: To observe the influence on the retinal ganglion cells induced by 2,450-MHz microwave. The radiant intensities were 10, 30 and 60 mW · cm–2. Methods: Retinal ganglion cells were cultured in vitro and divided into 4 groups, of which 3 were exposed to different intensities of microwaves and 1 was the control group. The morphological variation of cells was observed by invert microscope. The survival rate was assessed by trypan blue. Annexin V-PI 2-color flow cytometry was used to detect the percentage of earlier apoptosis cells after radiation. Results: The changes in the morphology of all cells were observed after radiation. The cell survival rates were reduced and the earlier apoptosis increased with growing microwave intensity. Conclusions: The 2,450-MHz microwave will cause damage to retinal ganglion cells in a dose-dependent manner.
Early Clinical Evaluation of AcrySof ReSTOR Multifocal Intraocular Lens for Treatment of Cataract
Authors: Bi Hongsheng , Cui Yan , Ma Xiaohua , Cai Wanting , Wang Guimin , Ji Peng , Xie Xiaofeng
Published: December 2007

Purpose: To evaluate the efficacy, safety and early visual quality of the AcrySof ReSTOR multifocal intraocular lens (IOL) following cataract surgery. Setting: Eye Center of Shandong University of Traditional Chinese Medicine, Jinan Shierming Eye Hospital, Jinan, Shandong, China. Methods:After small-incision phacoemulsification, AcrySof ReSTOR IOLs were implanted in 20 subjects (40 eyes, ReSTOR group). Monofocal IOLs were implanted in 18 subjects (36 eyes, control group). Three to six months following bilateral implantation, visual acuity, depth of focus, corneal astigmatism, contrast sensitivity, glare sensitivity, visual field and spherical aberration were compared between the groups. A subjective outcome questionnaire was also completed by the subjects. Results: Uncorrected near visual acuity 0.5 or better was achieved by 92.5% of the ReSTOR eyes. In the monofocal eyes, only 33.3% of the eyes achieved uncorrected near visual acuity of 0.5 or better. There was no statistical difference between corrected near, distance visual acuity, and uncorrected distance visual acuity in the 2 groups (p > 0.05). In patients with visual acuity 0.5 or better, the depth of focus was 4.87 ± 1.09 and 2.08 ± 0.69 dpt in the ReSTOR and control groups, respectively. The contrast sensitivity, glare sensitivity and visual field of both groups were similar (p > 0.05). The spherical aberration of the 2 groups was similar (t = –0.37, p = 0.71). Visual disturbances were minimal with only 1 patient in each group complaining of glare at night. Conclusion:The AcrySof ReSTOR multifocal IOL is a safe and effective treatment for cataracts.
Effect of Passive Cigarette Smoking on Colonic α7-Nicotinic Acetylcholine Receptors in TNBS-Induced Colitis in Rats
Authors: Sun Ya P. , Wang Hua H. , He Qun , Cho Chi H.
Published: December 2007

Background and Aims: Cigarette smoking affects colonic inflammation, but the exact mechanism by which it does so is unclear. The aim of this study was to investigate the underlying mechanism by examining the effect of cigarette smoking on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. Method: Experimental colitis was induced by administrating TNBS enema in Sprague-Dawley rats. The effect of cigarette smoking was assessed by measuring the colonic edema, mucosal lesion area, histopathological score, mucosal myeloperoxidase (MPO) activity and tumor necrosis factor-α (TNF-α). The expression of α7-nicotinic acetylcholine receptor (α7nAChR) was examined after cigarette smoking to identify whether the α7nAChR is involved in inflammation. Results: TNBS induced severe colitis as evidenced by increased colonic edema, mucosal lesion area, histopathological score, MPO activity, and TNF-α level. Inflammation was aggravated by cigarette smoke exposure. Colonic tissue expressed α7nAChR (0.41 ± 0.11), and TNBS up-regulated the receptor expression (0.46 ± 0.11), but the difference was not significant (p > 0.05). Cigarette smoking with 2 and 4% respectively significantly increased the expression of α7nAChR (0.55 ± 0.05 and 0.64 ± 0.08) (p < 0.05). Conclusions: The up-regulated expression of α7nAChR after exposure to cigarette smoking indicates that α7nAChR in colonic tissue may be involved in cigarette smoking damage in TNBS-induced colitis in rats.
Percutaneous Thrombin Embolization of a Ruptured Peripancreatic Pseudoaneurysm
Authors: Ward E.V.M. , Buckley O. , Doody O. , Govender P. , Conlon K. , Torreggiani W.C.
Published: December 2007

Peripancreatic pseudoaneurysm formation is a recognized complication of pancreatitis. When associated with an acute episode of pancreatitis, surgical treatment is often difficult due to the inflammatory process that surrounds the pseudoaneurysm. In the stable patient, transcatheter embolization is the treatment of choice of this complication. However, this is not always technically feasible, as the aneurysm may be supplied by small inaccessible branch vessels. Recently, percutaneous thrombin injection has been described as a possible alternative for pseudoaneurysms. This is generally performed under computed tomography guidance in stable patients with non-ruptured pseudoaneurysms. We describe an acutely ruptured peripancreatic pseudoaneurysm in a critically ill patient, in whom percutaneous thrombin injection under computed tomography guidance resulted in immediate stabilization and cure of the pseudoaneurysm.
The c.1-260C>T Promoter Variant of CD14 but Not the c.896A>G (p.D299G) Variant of Toll-Like Receptor 4 (TLR4) Genes Is Associated with Inflammatory Bowel Disease
Authors: Baumgart Daniel C. , Büning Carsten , Geerdts Lars , Schmidt Hartmut H. , Genschel Janine , Fiedler Thomas , Gentz Enno , Molnar Tomas , Nagy Ferenc , Lonovics Janos , Lochs Herbert , Wiedenmann Bertram , Nickel Renate , Witt Heiko , Dignass Axel
Published: December 2007

Background: Inflammatory bowel disease (IBD) results from an aberrant immune response to the indigenous intestinal flora in genetically susceptible hosts. Therefore, the study of candidate genes involved in host pathogen interactions is of key interest. Methods: In this two-center, retrospective German and Hungarian cohort study, patients with Crohn’s disease (CD) (n = 379; German n = 235, Hungarian n = 144) and ulcerative colitis (UC) (n = 263; German n = 145, Hungarian n = 118) and healthy controls (n = 605; German n = 403, Hungarian n = 202) were genotyped for the presence of the CD14 c.1-260C>T promoter variant and the TLR4 c.896A>G (p.D299G) variant by melting curve analysis using fluorescence resonance energy transfer probes. Data were stratified according to the presence of NOD2 (CARD15) mutations and a detailed genotype-phenotype analysis was performed. Results: In the German cohort the CD14 single-nucleotide polymorphism was associated with UC, but not CD (UC p = 0.016 vs. CD p = 0.190), while the opposite was found in the Hungarian cohort (UC p = 0.083 vs. CD p = 0.019). No association of IBD with the TLR4 single-nucleotide polymorphism was found in either cohort (UC p = 0.430, CD p = 0.783 vs. UC p = 0.745, CD p = 0.383). Conclusion: IBD appears to be associated with the CD14 c.1-260C>T promoter variant in Germans and Hungarians, but not with the TLR4 c.896A>G (p.D299G) variant.
A Multicenter Prospective Survey on Informed Consent for Gastrointestinal Endoscopy in China
Authors: Bai Yu , Gao Jun , Yang Yuanping , Long Feiwu , Jin Hai , Li Changqing , Zou Duo-Wu , Li Zhao-Shen
Published: December 2007

Background/Aim: Data on informed consent procedures in endoscopy centers in China are lacking. The aim of this study was to record the current status of informed consent procedures in four tertiary endoscopy centers in China. Methods: All patients underwent upper gastrointestinal endoscopic examinations in four tertiary endoscopy centers in China from August 2006 to October 2006. Data on patients’ age, gender, education level, type of endoscopic procedures, complication rates, and satisfaction were recorded prospectively. Results: Totally, 1,303 patients were included (mean age 47.7 years, 50.2% males, 88.3% outpatients, 13.1% with university education) and underwent 1,308 endoscopic procedures. Of these patients, 994 were informed prior to the endoscopic procedures; the remaining patients were not asked for their oral or written informed consent before the procedure. No serious complications occurred, but 9 patients were not satisfied with the procedures and 5 patients refused to complete the endoscopic examination. Conclusions: Gastrointestinal endoscopic examinations, especially diagnostic gastroscopy, are safe, carrying minimal patient risk, but the current practice of informed consent procedures in China is suboptimal. More efforts should be made to improve the standards of informed consent for endoscopic procedures in China.
Cholesterol-Lowering and Antioxidant Status-Improving Efficacy of Germinated Giant Embryonic Rice (Oryza sativa L.) in High Cholesterol-Fed Rats
Authors: Lee Yeon Ri , Kim Chae Eun , Kang Mi Young , Nam Seok Hyun
Published: December 2007

Background/Aims: The purpose of the current study is to investigate the influence of germinated giant embryonic rice consumption on the lipid metabolism and antioxidant system in rats fed a high-cholesterol diet. Methods: Four groups of rats were given a diet containing 1 g cholesterol/kg for 5 weeks. The control group only received a high-cholesterol diet, while the other 3 experimental groups received each of the diets made of germinated giant embryonic rice, giant embryonic rice, or conventional brown rice (hereafter referred to as GGE-D, GE-D, and BR-D, respectively). Plasma and hepatic lipid profiles were measured, and the antioxidant status of liver was examined. Results: The plasma HDL-cholesterol concentration was significantly higher in rats fed GGE-D compared with the source material (GE-D) or BR-D, while there were no differences in the plasma total cholesterol and triglyceride concentrations between the groups. Consequently, the atherogenic indices of the GGE-D and GE-D groups were significantly lower than for the other groups. The plasma and hepatic thiobarbituric acid-reactive substance levels were higher in rats in the order of those fed BR-D > GE-D > GGE-D. While superoxide dismutase and catalase were significantly activated in rats fed both GGE-D and GE-D, glutathione peroxidase was significantly and most effectively activated in those fed GGE-D. Conclusions: The current results indicate that consumption of germinated giant embryonic rice is effective in lowering atherosclerosis cardiovascular disease risk.
Impact of Plasma Tissue Inhibitor of Matrix Metalloproteinase-1 on Long-Term Survival in Patients with Colorectal Cancer
Authors: Yukawa Norio , Yoshikawa Takaki , Akaike Makoto , Sugimasa Yukio , Rino Yasushi , Masuda Munetaka , Imada Toshio
Published: December 2007

Tissue inhibitor of metalloproteinase-1 (TIMP-1) not only inhibits matrix metalloproteinases but also stimulates tumor growth. In this study, long-term follow-up results were analyzed to clarify the prognostic value of plasma TIMP-1. Preoperative plasma TIMP-1 was measured from peripheral blood samples of 87 Japanese patients with colorectal carcinoma. All the patients underwent surgical resection and were followed for 5 years prospectively. The median follow-up period was 70 months (60–79 months). The cutoff value of plasma TIMP-1 was set at 170 ng/ml based on the ROC curve. Sensitivity and specificity to predict 5-year survival was 66.7 and 55.0% with this cutoff value. In univariate analyses for overall survival, lymph node metastasis, serosal invasion, peritoneal metastasis, liver metastasis, metastasis to other distant organs and TIMP-1 were significant. In multivariate analyses, lymph node and liver metastases, metastasis to other distant organs and plasma TIMP-1 were independent prognosticators, but p values of TIMP-1 did not reach statistical significance. Our results suggested that the preoperative plasma TIMP-1 concentration could be a useful prognosticator of long-term survival in patients with colorectal carcinoma.
Oleate Induces a Myofibroblast-Like Phenotype in Mesangial Cells
Authors: Mishra Rangnath , Simonson Michael S.
Published: December 2007

Objective—

High circulating free fatty acids, commonly associated with obesity and insulin resistance, impair structure and function of the microvasculature. However, the mechanisms by which fatty acids cause microvascular remodeling are unclear. Using the mesangial cell model of microvascular pericytes, we demonstrate that the monounsaturated free fatty acid oleate induces a myofibroblast phenotype, an important cell fate transition in fibrotic remodeling of the extracellular matrix.

Materials and Results—

Oleate induced a time- and dose-dependent increase in secretion of collagen I and fibronectin. Oleate also induced the myofibroblast phenotype markers α smooth muscle actin and ED-A fibronectin, and the magnitude of marker protein expression was similar to that for transforming growth factor (TGF)-β. Oleate raised TGF-β secretion 2.2-fold, and processing of latent to bioactive TGF-β was also elevated. Oleate rapidly stimulated extracellular signal-regulated kinase1/2, and a pharmacological MEK inhibitor blocked TGF-β secretion and conversion to the myofibroblast phenotype. A neutralizing TGF-β antibody and a TGF-β receptor kinase inhibitor blocked oleate-induced collagen I, α smooth muscle actin, and ED-A fibronectin, suggesting that oleate-stimulated TGF-β was necessary for inducing myofibroblasts.

Conclusions—

Collectively, these results demonstrate that oleate can induce a myofibroblast phenotype in mesangial cells, which suggests a mechanism whereby elevated free fatty acids might promote microvascular remodeling in vivo.
Dual Regulation of Cofilin Activity by LIM Kinase and Slingshot-1L Phosphatase Controls Platelet-Derived Growth Factor–Induced Migration of Human Aortic Smooth Muscle Cells
Authors: San Martín Alejandra , Lee Moo Yeol , Williams Holly C. , Mizuno Kensaku , Lassègue Bernard , Griendling Kathy K.
Published: December 2007

Platelet-derived growth factor (PDGF) plays a central role in vascular healing, atherosclerosis, and restenosis, partly by stimulating vascular smooth muscle cell (VSMC) migration. Migration requires rapid turnover of actin filaments, which is partially controlled by cofilin. Although cofilin is negatively regulated by Ser3 phosphorylation, the upstream signaling pathways have not been defined, nor has its role in VSMC migration been studied. We hypothesized that PDGF-induced migration of VSMCs involves cofilin activation and that this is regulated by the serine kinase LIM kinase (LIMK) and the novel phosphatase Slingshot (SSH)1L. In human VSMCs, stimulation with PDGF increased G-actin incorporation into the actin cytoskeleton. PDGF transiently activated the cofilin kinase, LIMK, with a peak at 5 minutes. However, cofilin was dephosphorylated between 5 and 45 minutes, with a maximum of 43±5% dephosphorylation at 30 minutes, suggesting that PDGF also activates a cofilin phosphatase. We found that VSMCs express SSH1L, which is induced and activated (564±73 versus 1021±141 picomoles of PO
4
;
P
=0.015) by PDGF. Of importance, small interfering RNA directed against SSH1L blocked cofilin dephosphorylation and decreased migration (528±33 versus 318±25 cells/field;
P
<0.01). Taken together, our results suggest that PDGF participates in actin dynamics by dual regulation of cofilin activity via LIMK and SSH1L.
The Cell Cycle Factor E2F-1 Activates Bnip3 and the Intrinsic Death Pathway in Ventricular Myocytes
Authors: Yurkova Natalia , Shaw James , Blackie Karen , Weidman Danielle , Jayas Ravi , Flynn Bryan , Kirshenbaum Lorrie A.
Published: December 2007

The cell cycle factor E2F-1 is known to regulate a variety of cellular processes including apoptosis. Previously we showed that disruption of Rb–E2F-1 complexes provoked apoptosis of postmitotic adult and neonatal ventricular myocytes; however, the underlying mechanism was undetermined. In this report, we show that E2F-1 provokes cell death of ventricular myocytes through a mechanism that directly impinges on the intrinsic death pathway. Furthermore, we show mechanistically that the hypoxia-inducible death factor Bnip3 is a direct transcriptional target of E2F-1 that is necessary and sufficient for E2F-1–induced cell death. Expression of E2F-1 resulted in a 4.9-fold increase (
P
<0.001) in nucleosomal DNA fragmentation and cell death by Hoechst 33258 dye and vital staining. E2F-1 provoked mitochondrial perturbations that were consistent with permeability transition pore opening. As determined by quantitative real-time PCR analysis, a 6.2-fold increase (
P
<0.001) in endogenous Bnip3 gene transcription was observed in cells expressing wild-type E2F-1 but not in cells expressing a mutation of E2F-1 defective for DNA binding. Rb, the principle regulator of cellular E2F-1 activity, was proteolytically cleaved and inactivated in ventricular myocytes during hypoxia. Consistent with the proteolytic cleavage of Rb, chromatin immunoprecipitation analysis revealed increased binding of E2F-1 to the Bnip3 promoter during hypoxia, a finding concordant with the induction of Bnip3 gene transcription. The Bnip3 homolog Nix/Bnip3L was unaffected in ventricular myocytes by either E2F-1 or hypoxia. Genetic knockdown of E2F-1 or expression of a caspase-resistant form of Rb suppressed basal and hypoxia-inducible Bnip3 gene transcription. Loss-of-function mutations of Bnip3 defective for mitochondrial membrane insertion or small interference RNA directed against Bnip3 suppressed cell death signals elicited by E2F-1. To our knowledge, the data provide the first direct evidence that activation of the intrinsic mitochondrial death pathway by E2F-1 is mutually dependent on and obligatorily linked to the transcriptional activation of Bnip3.
Factors Associated With the Decision to Hospitalize Patients After Transient Ischemic Attack Before Publication of Prediction Rules
Authors: Josephson S. Andrew , Sidney Stephen , Pham Trinh N. , Bernstein Allan L. , Johnston S. Claiborne
Published: December 2007

Background and Purpose—

One important criterion for hospitalizing patients after transient ischemic attack (TIA) is the short-term risk of stroke. Before publication of prediction rules for stroke after TIA, physician judgment was required to make a decision about hospitalization. We sought to identify factors associated with the decision to admit patients with TIA from the emergency department (ED) and to see whether those at highest risk of stroke were selected for admission.

Methods—

All patients diagnosed with TIA in the ED of 16 hospitals in the Kaiser-Permanente Medical Care Plan over a 1-year period before publication of prediction rules were included (n=1707). Risk of subsequent stroke was stratified according to a validated prediction rule (ABCD
2
score), and the decision to admit was correlated with these risk scores. Factors associated with admission in univariate analysis were included in a logistic regression model.

Results—

Overall, 243 patients with TIA (14%) were admitted. Admission weakly correlated with the ABCD
2
score (rank biserial
R
2
=0.036; 10.0% at low 2-day risk of stroke admitted versus 20.3% at high risk). Seven variables were independently associated with a decision to admit after TIA: prior TIA, speech impairment, weakness, gait disturbance, history of atrial fibrillation, symptoms on arrival to ED, and use of ticlopidine.

Conclusions—

In this cohort of patients with TIA, the decision to admit was weakly correlated with risk of subsequent stroke as measured by the ABCD
2
score, and several risk factors for stroke were not important for the decision to admit. Before publication of prediction rules for stroke after TIA, physicians were not identifying the majority of patients at highest risk of stroke for admission.
Prediction and Optimization of Mechanical Properties of Polypropylene/Waste Tire Powder Blends using a Hybrid Artificial Neural Network-Genetic Algorithm (GA-ANN)
Authors: Balasubramanian Maridass , Paglicawan Marissa A. , Zhang Zhen-Xiu , Sung Hyo Lee  , Xin Zhen-Xiang , Jin Kuk Kim
Published: December 2007

Blends of Polypropylene (PP) and waste ground rubber tire powder are studied with respect to the effect of ethylene—propylene—diene monomer (EPDM) and polypropylene grafted maleic anhydride (PP-g-MA) compatibilizer content by using the Design of Experiments methodology, whereby the effect of the four polymers content on the final mechanical properties are predicted. Uniform design method is especially adopted for its advantages. Optimization is done using hybrid Artificial Neural Network-Genetic Algorithm technique. A rubber formulary with respect to the four ingredients are optimized having maximum tensile strength and then compared with a blend predicted to have maximum elongation at break. It is concluded that the blends show fairly good properties provided that it has a relatively higher concentration of PP-g-MA and EPDM content. SEM investigations also corroborates with the observed mechanical properties. A quantitative relationship is then shown between the material concentration and the mechanical properties as a set of contour plots, which are then tested and confirmed experimentally to conform to the optimum blend ratio.
The Practice of Nursing Science: Crossing Boundaries
Authors: Reed Pamela G.
Published: December 2007

This column presents descriptions of how four nurse researchers practice science, based upon a framework constructed to depict key dimensions in the practice of nursing science. Emphasis is given to the role of theory in science.
Yes, Virginia, Nursing Does Have Laws
Authors: Webber Pamela B.
Published: December 2007

In this article the author explores the possibility of the emergence of nursing laws as a natural consequence of the maturation and evolution of selected areas of nursing knowledge. To support this proposition, the evolution of social and scientific laws and their meanings are discussed. In addition, the roles that empirical validation and logical adequacy play in epistemological development, including the development of discipline-specific laws, are explored. Two areas of nursing knowledge in which laws may be emerging, as well as the foundation of these laws, are identified.
Analytical Modeling of Sandwich Beams with Functionally Graded Core
Authors: Apetre N.A. , Sankar B.V. , Ambur D.R.
Published: December 2007

This study investigates several available sandwich beam theories for their suitability of application to one-dimensional sandwich plates with functionally graded core. Two equivalent single-layer theories based on assumed displacements, a higher-order theory, and the Fourier—Galerkin method are compared. The results are also compared with the finite element analysis. The core of the sandwich panel is functionally graded such that the density, and hence its stiffness, vary through the thickness. The variation of core Young's modulus is represented by a differentiable function in the thickness coordinate, but the Poisson's ratio is kept constant. A very good agreement is found among the Fourier—Galerkin method, the higher-order theory, and the finite element analysis.
Cytotoxic T lymphocytes overcome Bcl-2 inhibition: target cells contribute to their own demise
Authors: Goping Ing Swie , Sawchuk Tracy , Rieger Aja , Shostak Irene , Bleackley R. Chris
Published: December 2007

Cytotoxic T lymphocytes (CTLs) eliminate pathogenic cells in large part through the activity of the serine protease granzyme B (grB). However, while the apoptotic activity of grB is blocked by over-expression of Bcl-2, CTLs can still kill target cells through an ill-defined Bcl-2–independent pathway. In this report, we have identified key modulators of this Bcl-2–independent cell-death pathway, which is induced by CTLs and not purified components. Surprisingly, activation of this pathway is reliant on grB. Furthermore, this novel pathway requires mitochondrial contribution through triggering of permeability transition and generation of reactive oxygen species, yet is functional in the absence of Bax/Bak. This pathway stimulates movement of target cell mitochondria toward the point of contact with the CTLs and importantly, inhibition of this directed movement attenuates killing. Therefore, we propose that CTLs initiate a target cell response that activates multiple mitochondrial pathways. This ensures that CTLs can eliminate those target cells that have compromised apoptotic potential due to overexpression of Bcl-2.
BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors
Authors: Copland Mhairi , Pellicano Francesca , Richmond Linda , Allan Elaine K. , Hamilton Ashley , Lee Francis Y. , Weinmann Roberto , Holyoake Tessa L.
Published: December 2007

Chronic myeloid leukemia (CML), a hematopoietic stem-cell disorder, cannot be eradicated by conventional chemotherapy or the tyrosine kinase inhibitor imatinib mesylate (IM). To target CML stem/progenitor cells, we investigated BMS-214662, a cytotoxic farnesyltransferase inhibitor, previously reported to kill nonproliferating tumor cells. IM or dasatinib alone reversibly arrested proliferation of CML stem/progenitor cells without inducing apoptosis. In contrast, BMS-214662, alone or in combination with IM or dasatinib, potently induced apoptosis of both proliferating and quiescent CML stem/progenitor cells with less than 1% recovery of Philadelphia-positive long-term culture-initiating cells. Normal stem/progenitor cells were relatively spared by BMS-214662, suggesting selectivity for leukemic stem/progenitor cells. The ability to induce selective apoptosis of leukemic stem/progenitor cells was unique to BMS-214662 and not seen with a structurally similar agent BMS-225975. BMS-214662 was cytotoxic against CML blast crisis stem/progenitor cells, particularly in combination with a tyrosine kinase inhibitor and equally effective in cell lines harboring wild-type vs mutant BCR-ABL, including the T315I mutation. This is the first report of an agent with activity in resistant and blast crisis CML that selectively kills CML stem/progenitor cells through apoptosis and offers potential for eradication of chronic phase CML.
The rituximab-PKCζ/Raf-1/mTOR connection
Authors: Bonavida Benjamin
Published: December 2007

In this issue of Blood, Leseux and colleagues report rituximab-mediated inhibition of PKCζ activity in follicular lymphoma (FL) resulting in the inhibition of Raf-1 and mTOR signaling pathways and leading to inhibition of tumor cell proliferation.
TaMSH7: A cereal mismatch repair gene that affects fertility in transgenic barley (Hordeum vulgare L.)
Authors: Lloyd Andrew H , Milligan Andrew S , Langridge Peter , Able Jason A
Published: December 2007

Background

Chromosome pairing, recombination and DNA repair are essential processes during meiosis in sexually reproducing organisms. Investigating the bread wheat (Triticum aestivum L.) Ph2 (Pairing homoeologous) locus has identified numerous candidate genes that may have a role in controlling such processes, including TaMSH7, a plant specific member of the DNA mismatch repair family.

Results

Sequencing of the three MSH7 genes, located on the short arms of wheat chromosomes 3A, 3B and 3D, has revealed no significant sequence divergence at the amino acid level suggesting conservation of function across the homoeogroups. Functional analysis of MSH7 through the use of RNAi loss-of-function transgenics was undertaken in diploid barley (Hordeum vulgare L.). Quantitative real-time PCR revealed several T0 lines with reduced MSH7 expression. Positive segregants from two T1 lines studied in detail showed reduced MSH7 expression when compared to transformed controls and null segregants. Expression of MSH6, another member of the mismatch repair family which is most closely related to the MSH7 gene, was not significantly reduced in these lines. In both T1 lines, reduced seed set in positive segregants was observed.

Conclusion

Results presented here indicate, for the first time, a distinct functional role for MSH7 in vivo and show that expression of this gene is necessary for wild-type levels of fertility. These observations suggest that MSH7 has an important function during meiosis and as such remains a candidate for Ph2.
The global distribution of fatal pesticide self-poisoning: Systematic review
Authors: Gunnell David , Eddleston Michael , Phillips Michael R , Konradsen Flemming
Published: December 2007

Background

Evidence is accumulating that pesticide self-poisoning is one of the most commonly used methods of suicide worldwide, but the magnitude of the problem and the global distribution of these deaths is unknown.

Methods

We have systematically reviewed the worldwide literature to estimate the number of pesticide suicides in each of the World Health Organisation's six regions and the global burden of fatal self-poisoning with pesticides. We used the following data sources: Medline, EMBASE and psycINFO (1990–2007), papers cited in publications retrieved, the worldwide web (using Google) and our personal collections of papers and books. Our aim was to identify papers enabling us to estimate the proportion of a country's suicides due to pesticide self-poisoning.

Results

We conservatively estimate that there are 258,234 (plausible range 233,997 to 325,907) deaths from pesticide self-poisoning worldwide each year, accounting for 30% (range 27% to 37%) of suicides globally. Official data from India probably underestimate the incidence of suicides; applying evidence-based corrections to India's official data, our estimate for world suicides using pesticides increases to 371,594 (range 347,357 to 439,267). The proportion of all suicides using pesticides varies from 4% in the European Region to over 50% in the Western Pacific Region but this proportion is not concordant with the volume of pesticides sold in each region; it is the pattern of pesticide use and the toxicity of the products, not the quantity used, that influences the likelihood they will be used in acts of fatal self-harm.

Conclusion

Pesticide self-poisoning accounts for about one-third of the world's suicides. Epidemiological and toxicological data suggest that many of these deaths might be prevented if (a) the use of pesticides most toxic to humans was restricted, (b) pesticides could be safely stored in rural communities, and (c) the accessibility and quality of care for poisoning could be improved.
Resource allocation of in vitro fertilization: a nationwide register-based cohort study
Authors: Klemetti Reija , Gissler Mika , Sevón Tiina , Hemminki Elina
Published: December 2007

Background

Infertility is common and in vitro fertilization (IVF) is a widely used treatment. In IVF the need increases and the effectiveness and appropriateness decrease by age. The purpose of this study was to describe allocation of resources for IVF by women's age, socioeconomic position, area of residence and treatment sector (public vs. private) and to discuss how fairly the IVF resources are allocated in Finland.

Methods

Women who received IVF between 1996 and 1998 (N = 9175) were identified from the reimbursement records of the Social Insurance Institution (SII). Information on IVF women's background characteristics came from the Central Population Register and the SII, on treatment costs from IVF clinics and the SII, and on births from the Medical Birth Register. The main outcome measures were success of IVF by number of cycles and treated women, expenditures per IVF cycles, per women, per live-birth, and per treatment sector, and private and public expenditures. Expenditures were estimated from health care visits and costs.

Results

During a mean period of 1.5 years, older women (women aged 40 or older) received 1.4 times more IVF treatment cycles than younger women (women aged below 30). The success rate decreased by age: from 22 live births per 100 cycles among younger women to 6 per 100 among older women. The mean cost of a live birth increased by age: compared to younger women, costs per born live birth of older women were 3-fold. Calculated by population, public expenditure was allocated most to young women and women from the highest socioeconomic position. Regional differences were not remarkable.

Conclusion

Children of older infertile women involve more expense due to the lower success rates of IVF. Socioeconomic differences suggest unfair resource allocation in Finland.
Oral health service utilization by elderly beneficiaries of the Mexican Institute of Social Security in México city
Authors: Sánchez-García Sergio , de la Fuente-Hernández Javier , Juárez-Cedillo Teresa , Mendoza José Manuel Ortega , Reyes-Morales Hortensia , Solórzano-Santos Fortino , García-Peña Carmen
Published: December 2007

Background

The aging population poses a challenge to Mexican health services. The aim of this study is to describe recent oral health services utilization and its association with socio-demographic characteristics and co-morbidity in Mexican Social Security beneficiaries 60 years and older.

Methods

A sample of 700 individuals aged 60+ years was randomly chosen from the databases of the Mexican Institute of Social Security (IMSS). These participants resided in the southwest of Mexico City and made up the final sample of a cohort study for identifying risk factors for root caries in elderly patients. Sociodemographic variables, presence of cognitive decline, depression, morbidity, medication consumption, and utilization of as well as reasons for seeking oral health services within the past 12 months were collected through a questionnaire. Clinical oral assessments were carried out to determine coronal and root caries experience.

Results

The sample consisted of 698 individuals aged 71.6 years on average, of whom 68.3% were women. 374 participants (53.6%) had made use of oral health services within the past 12 months. 81% of those who used oral health services sought private medical care, 12.8% sought social security services, and 6.2% public health services. 99.7% had experienced coronal caries and 44.0% root caries. Female sex (OR = 2.0), 6 years' schooling or less (OR = 1.4), and caries experience in more than 22 teeth (OR = 0.6) are factors associated with the utilization of these services.

Conclusion

About half the elderly beneficiaries of social security have made use of oral health services within the past 12 months, and many of them have to use private services. Being a woman, having little schooling, and low caries experience are factors associated with the use of these services.
Genomic and gene regulatory signatures of cryptozoic adaptation: Loss of blue sensitive photoreceptors through expansion of long wavelength-opsin expression in the red flour beetle Tribolium castaneum
Authors: Jackowska Magdalena , Bao Riyue , Liu Zhenyi , McDonald Elizabeth C , Cook Tiffany A , Friedrich Markus
Published: December 2007

Background

Recent genome sequence analysis in the red flour beetle Tribolium castaneum indicated that this highly crepuscular animal encodes only two single opsin paralogs: a UV-opsin and a long wavelength (LW)-opsin; however, these animals do not encode a blue (B)-opsin as most other insects. Here, we studied the spatial regulation of the Tribolium single LW- and UV-opsin gene paralogs in comparison to that of the five opsin paralogs in the retina of Drosophila melanogaster.

Results

In situ hybridization analysis reveals that the Tribolium retina, in contrast with other insect retinas, constitutes a homogenous field of ommatidia that have seven LW-opsin expressing photoreceptors and one UV-/LW-opsin co-expressing photoreceptor per eye unit. This pattern is consistent with the loss of photoreceptors sensitive to blue wavelengths. It also identifies Tribolium as the first example of a species in insects that co-expresses two different opsins across the entire retina in violation of the widely observed "one receptor rule" of sensory cells.

Conclusion

Broader studies of opsin evolution in darkling beetles and other coleopteran groups have the potential to pinpoint the permissive and adaptive forces that played a role in the evolution of vision in Tribolium castaneum.
The Role of the Human Orbitofrontal Cortex in Taste and Flavor Processing
Authors: SMALL DANA M. , BENDER GENEVIEVE , VELDHUIZEN MARIA G. , RUDENGA KRISTIN , NACHTIGAL DANIELLE , FELSTED JENNIFER
Published: December 2007

Abstract: The human orbitofrontal cortex (OFC) plays an important role in representing taste, flavor, and food reward. The primary role of the OFC in taste is thought to be the encoding of affective value and the computation of perceived pleasantness. The OFC also encodes retronasal olfaction and oral somatosensation. During eating, distinct sensory inputs fuse into a unitary flavor percept, and there is evidence that this percept is encoded in the orbital cortex. Studies examining the effect of internal state on neural representation of food and drink further suggest that processing in the OFC is critical for representing the reward value of foods. Thus, it is likely that, in addition to serving as higher‐order gustatory cortex, the OFC integrates multiple sensory inputs and computes reward value to guide feeding behavior.
Taste in the Medial Orbitofrontal Cortex of the Macaque
Authors: PRITCHARD THOMAS C. , SCHWARTZ GARY J. , SCOTT THOMAS R.
Published: December 2007

Abstract: Taste activates about 6% of the neurons in the anterior insula (primary taste cortex) of the macaque. The anterior insula has many direct and indirect projections to the orbitofrontal cortex (OFC), including the caudolateral OFC (clOFC), where only 2% of the neurons respond to taste. We have identified a 12‐mm2 region in the medial OFC (mOFC) where taste represents 7–28% of the population. This rich trove of taste cells has functional characteristics typical of both the insular cortex that projects to it and the clOFC to which it projects. Mean spontaneous rate was 3.1 spikes/s, nearly identical to that in the insula, but double that of the clOFC. In the mOFC, 19% of the taste cells also responded to other modalities, most commonly olfaction and touch, slightly less than the 27% in the clOFC. The distribution of best stimulus neurons was almost even across the four prototypical stimuli in the mOFC, as in insula, but discrepant from the clOFC, where sugar responsiveness dominated. The broadly tuned taste neurons in the mOFC were similar to those in the insula and strikingly different from the more specialized cells of the clOFC. Whereas the responsiveness to the taste of a satiating stimulus declines among the narrowly tuned clOFC cells, satiety has much less impact on the responsiveness of mOFC neurons. The mOFC is a robust area worthy of exploration for its involvement in gustatory coding, the amalgamation of sensory inputs to create flavor, and the hedonics that guide feeding.
Orbital Versus Dorsolateral Prefrontal Cortex
Authors: ZALD DAVID H.
Published: December 2007

Abstract: Content differentiation models posit that different areas of the prefrontal cortex perform similar operations but differ in terms of the content that is operated on. For example, it has been suggested that the orbitofrontal cortex (OFC) and the dorsolateral prefrontal cortex (DLPFC) perform similar working memory or inhibitory operations, but on different types of content (e.g., reward versus spatial or feature‐based versus abstract). In contrast to the above models, process differentiation models posit that different areas of the prefrontal cortex perform fundamentally different operations. Surprisingly, discussions of these dueling models rarely incorporate information about anatomy. The only exception is that advocates of content differentiation models appropriately note that different parts of the prefrontal cortex receive different afferents. Yet, an examination of the anatomy of the OFC and the DLPFC reveal numerous differences in cortical structure and interneuron composition. These structural differences necessitate that the OFC and the DLPFC will have strikingly different computational features. Given such computational differences, strong versions of content differentiation models are untenable. While overarching themes may help explain the operations in both the OFC and the DLPFC, the specific operations performed in the two regions are likely to be both quantitatively and qualitatively different in nature.
Keynote Address: Revaluing the Orbital Prefrontal Cortex
Authors: DOLAN R. J.
Published: December 2007

Abstract:  The importance of orbitofrontal cortex (OFC) in human behavioral regulation is no longer a matter of dispute, though its precise role remains a matter of ongoing investigation. It is ironic that this revaluation of OFC required a major departure from a historical nadir, during which it was viewed as redundant or “silent cortex,” a situation that prevailed even up to the latter half of the 20th century. The increasing wealth of data from diverse fields within neuroscience now provides an unambiguous testament to the importance of this cortical region in behavioral regulation and cognition in general.
Orbitofrontal Cortex and Amygdala Contributions to Affect and Action in Primates
Authors: MURRAY ELISABETH A. , IZQUIERDO ALICIA
Published: December 2007

Abstract: The amygdala and orbitofrontal cortex (OFC) work together as part of the neural circuitry guiding goal‐directed behavior. This chapter explores the way in which the amygdala and OFC contribute to emotion and reward processing in macaque monkeys, taking into account recent methodological and conceptual advances. Although direct functional interaction of the amygdala and OFC is necessary for some types of stimulus–reward associations, it is not necessary for others. Both regions contribute to the expression of defensive responses to a potential predator. Contrary to the prevailing view, the amygdala and OFC make distinct contributions to emotional responses and reward processing.
The Role of the Orbitofrontal Cortex in Sensory‐Specific Encoding of Associations in Pavlovian and Instrumental Conditioning
Authors: DELAMATER ANDREW R.
Published: December 2007

Abstract:  A wide variety of associative learning tasks have been employed to assess the functional role of the orbitofrontal cortex (OFC) and related structures in learning. Many of these tasks were designed to assess the learning of highly specific associations between Pavlovian conditioned stimuli (or instrumental responses) and the sensory properties of reinforcement (i.e., sensory‐specific associations). Current research suggests that OFC lesions impair behavioral control by these sensory‐specific associations in unconditioned stimulus (US) devaluation, differential outcome, and Pavlovian‐to‐instrumental transfer experiments. In addition, although the OFC has been shown to be important in conditioned reinforcement but not in potentiated feeding tasks, versions of these tasks that assess control by sensory‐specific associations have either not been run or they have not examined the effects of OFC lesions. Thus, firm conclusions from conditioned reinforcement and potentiated feeding studies cannot yet be drawn. Furthermore, studies examining the OFC's involvement in reversal learning have also suggested that associations between stimuli and reinforcement importantly depend upon a functioning OFC, possibly because this structure is needed to generate outcome expectancies useful in the computation of prediction errors ultimately used to “update” associations elsewhere (e.g., basolateral amygdala). Other work has shown that both original and reversed sensory‐specific associations can control performance after different time delays following reversal learning. This suggests that structures outside of the OFC may be involved in the storage of originally acquired associations. Overall, this review makes clear that the OFC plays an important role in the encoding of sensory‐specific associations in a wide variety of learning tasks.
The Orbitofrontal Cortex, Real‐World Decision Making, and Normal Aging
Authors: DENBURG NATALIE L. , COLE CATHERINE A. , HERNANDEZ MICHAEL , YAMADA TORRICIA H. , TRANEL DANIEL , BECHARA ANTOINE , WALLACE ROBERT B.
Published: December 2007

Abstract:  The present series of three studies aims at investigating the hypothesis that some seemingly normal older persons have deficits in reasoning and decision making due to dysfunction in a neural system which includes the ventromedial prefrontal cortices. This hypothesis is relevant to the comprehensive study of aging, and also addresses the question of why so many older adults fall prey to fraud. To our knowledge, this work represents the first of its kind to begin to identify, from an individual‐differences perspective, the behavioral, psychophysiological, and consumer correlates of defective decision making among healthy older adults. Our findings, in a cross‐sectional sample of community‐dwelling participants, demonstrate that a sizeable subset of older adults (approximately 35–40%) perform disadvantageously on a laboratory measure of decision making that closely mimics everyday life, by the manner in which it factors in reward, punishment, risk, and ambiguity. These same poor decision makers display defective autonomic responses (or somatic markers), reminiscent of that previously established in patients with acquired prefrontal lesions. Finally, we present data demonstrating that poor decision makers are more likely to fall prey to deceptive advertising, suggesting compromise of real‐world judgment and decision‐making abilities.