bluuebunny/crossref_metadata_2025 huggingface dataset:
Barium Plateau Potentials of CA1 Pyramidal Neurons Elicit All-or-None Extracellular Alkaline Shifts Via the Plasma Membrane Calcium ATPase
Authors: Makani Sachin , Chesler Mitchell
Published: July 2010

In many brain regions, synchronous neural activity causes a rapid rise in extracellular pH. In the CA1 region of hippocampus, this population alkaline transient (PAT) enhances responses from postsynaptic, pH-sensitive N-methyl-d-aspartate (NMDA) receptors. Recently, we showed that the plasma membrane Ca2+-ATPase (PMCA), a ubiquitous transporter that exchanges internal Ca2+for external H+, is largely responsible for the PAT. It has also been shown that a PAT can be generated after replacing extracellular Ca2+with Ba2+. The cause of this PAT is unknown, however, because the ability of the mammalian PMCA to transport Ba2+is unclear. If the PMCA did not carry Ba2+, a different alkalinizing source would have to be postulated. Here, we address this issue in mouse hippocampal slices, using concentric (high-speed, low-noise) pH microelectrodes. In Ba2+-containing, Ca2+-free artificial cerebrospinal fluid, a single antidromic shock to the alveus elicited a large (0.1–0.2 unit pH), “all-or-none” PAT in the CA1 cell body region. In whole cell current clamp of single CA1 pyramidal neurons, the same stimulus evoked a prolonged plateau potential that was similarly all-or-none. Using this plateau as the voltage command in other cells, we recorded Ba2+-dependent surface alkaline transients (SATs). The SATs were suppressed by adding 5 mM extracellular HEPES and abolished when carboxyeosin (a PMCA inhibitor) was in the patch pipette solution. These results suggest that the PAT evoked in the presence of Ba2+is caused by the PMCA and that this transporter is responsible for the PAT whether Ca2+or Ba2+is the charge carrying divalent cation.
Effect of Trial Order and Error Magnitude on Motor Learning by Observing
Authors: Brown Liana E. , Wilson Elizabeth T. , Obhi Sukhvinder S. , Gribble Paul L.
Published: July 2010

Watching an actor make reaching movements in a perturbing force field provides the observer with information about how to compensate for that force field. Here we asked two questions about the nature of information provided to the observer. Is it important that the observer learn the difference between errant (curved) movements and goal (straight) movements by watching the actor progress in a relatively orderly fashion from highly curved to straight movements over a series of trials? Or is it sufficient that the observer sees only reaching errors in the force field (FF)? In the first experiment, we found that observers performed better if they observed reaches in a FF that was congruent, rather than incongruent, with the FF used in a later test. Observation-trial order had no effect on performance, suggesting that observers understood the goal in advance and perhaps learned about the force-field by observing movement curvature. Next we asked whether observers learn optimally by observing the actor's mistakes (high-error trials), if they learn by watching the actor perform with expertise in the FF (low-error trials), or if they need to see contrast between errant and goal behavior (a mixture of both high- and low-error trials). We found that observers who watched high-error trials were most affected by observation but that significant learning also occurred if observers watched only some high-error trials. This result suggests that observers learn to adapt their reaching to an unpredictable FF best when they see the actor making mistakes.
Analysis of the Relationship between Changes in Meteorological Conditions and the Variation in Summer Ozone Levels over the Central Kanto Area
Authors: Khiem Mai , Ooka Ryozo , Huang Hong , Hayami Hiroshi , Yoshikado Hiroshi , Kawamoto Yoichi
Published: July 2010

An increasing trend in ground‐level ozone (O3) concentrations has recently been recognized in Japan, although concentrations of ozone precursors, nitrogen oxides (NOx), volatile organic compounds (VOCs) and nonmethane hydrocarbons (NMHCs) have decreased. In this paper, the relationship between meteorological factors (temperature and wind speed) and ground‐level ozone concentrations in the summer over the central Kanto area of Japan was examined using both statistical analyses and numerical models. The Fifth‐Generation NCAR/Penn State Mesoscale Model (MM5) and the Community Multiscale Air Quality (CMAQ) model were employed in this study. It was found that there is a close relationship between meteorological conditions and ground‐level ozone concentrations over the central Kanto area. In summer, up to 84% of the long‐term variation in peak ozone concentrations may be accounted for by changes in the seasonally averaged daily maximum temperature and seasonally averaged wind speed, while about 70% of the recent short‐term variation in peak ozone depends on the daily maximum temperature and the daily averaged wind speed. The results of numerical simulations also indicate that urban heat island (UHI) phenomena can play an important role in the formation of high ozone concentrations in this area.
The Role of Genetic Variation Near Interferon-Kappa in Systemic Lupus Erythematosus
Authors: Harley Isaac T. W. , Niewold Timothy B. , Stormont Rebecca M. , Kaufman Kenneth M. , Glenn Stuart B. , Franek Beverly S. , Kelly Jennifer A. , Kilpatrick Jeffrey R. , Hutchings David , Divers Jasmin , Bruner Gail R. , Edberg Jeffrey C. , McGwin Gerald , Petri Michelle A. , Ramsey-Goldman Rosalind , Reveille John D. , Vilá-Pérez Luis M. , Merrill Joan T. , Gilkeson Gary S. , Vyse Timothy J. , Alarcón-Riquelme Marta E. , Cho Soo-Kyung , Jacob Chaim O. , Alarcón Graciela S. , Moser Kathy L. , Gaffney Patrick M. , Kimberly Robert P. , Bae Sang-Cheol , Langefeld Carl D. , Harley John B. , Guthridge Joel M. , James Judith A.
Published: July 2010

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by increased type I interferons (IFNs) and multiorgan inflammation frequently targeting the skin. IFN-kappa is a type I IFN expressed in skin. A pooled genome-wide scan implicated theIFNKlocus in SLE susceptibility. We studiedIFNKsingle nucleotide polymorphisms (SNPs) in 3982 SLE cases and 4275 controls, composed of European (EA), African-American (AA), and Asian ancestry. rs12553951C was associated with SLE in EA males (odds ratio=1.93,P=2.5×10−4), but not females. Suggestive associations with skin phenotypes in EA and AA females were found, and these were also sex-specific.IFNKSNPs were associated with increased serum type I IFN in EA and AA SLE patients. Our data suggest a sex-dependent association betweenIFNKSNPs and SLE and skin phenotypes. The serum IFN association suggests thatIFNKvariants could influence type I IFN producing plasmacytoid dendritic cells in affected skin.
Receptor Activator of NF-κB Ligand Enhances Breast Cancer–Induced Osteolytic Lesions through Upregulation of Extracellular Matrix Metalloproteinase Inducer/CD147
Authors: Rucci Nadia , Millimaggi Danilo , Mari Marianna , Del Fattore Andrea , Bologna Mauro , Teti Anna , Angelucci Adriano , Dolo Vincenza
Published: July 2010

Breast cancer shows a strong predilection to metastasize to bone. Cell surface glycoprotein extracellular matrix metalloproteinase inducer (EMMPRIN)/CD147 induces metalloproteinases (MMP) and vascular endothelial growth factor (VEGF), which may support osteoclastic activity and increased incidence of breast cancer bone metastases. In support of this hypothesis, we observed that MDA-MB-231 human breast tumor cells engineered to overexpress EMMPRIN strongly induced osteolytic lesions in immunodeficient mice, which was blunted by in vivo treatment with an EMMPRIN blocking antibody. Similarly, these cells exhibited increased expression of MMP-9 and VEGF relative to control cells. Treatment of MDA-MB-231 cells with the osteoclastogenic cytokine receptor activator of NF-κB ligand (RANKL) upregulated EMMPRIN expression with a parallel increase of MMP-9 and VEGF. Conditioned medium from osteoblasts similarly increased EMMPRIN, MMP-9, and VEGF expression in cells. Osteoblast treatment with the RANKL decoy receptor osteoprotegerin abolished this effect. EMMPRIN overexpression stimulated MDA-MB-231 cell invasion but not proliferation. Conversely, small interfering RNA–mediated knockdown of EMMPRIN downregulated MMP-9 and VEGF basal expression and RANKL-stimulated expression, and reduced cell invasion. Our results argue that EMMPRIN drives breast cancer–induced osteolytic lesions and that activation of the RANKL pathway increases EMMPRIN in osteotropic tumor cells, in turn enhancing tumor-induced bone resorption. Cancer Res; 70(15); 6150–60. ©2010 AACR.
Monitoring of Natural Killer Cell Immunotherapy Using Noninvasive Imaging Modalities
Authors: Jha Priyanka , Golovko Daniel , Bains Sukhmine , Hostetter Daniel , Meier Reinhard , Wendland Michael F. , Daldrup-Link Heike E.
Published: July 2010

Cancer immunotherapies can be guided by cellular imaging techniques, which can identify the presence or absence of immune cell accumulation in the tumor tissue in vivo and in real time. This review summarizes various new and evolving imaging techniques employed for tracking and monitoring of adoptive natural killer cell immunotherapies. Cancer Res; 70(15); 6109–13. ©2010 AACR.
Antigen-Experienced CD4+ T Cells Limit Naïve T-Cell Priming in Response to Therapeutic VaccinationIn vivo
Authors: Schiering Chris , Guarnerio Jlenia , Basso Veronica , Muzio Luca , Mondino Anna
Published: July 2010

CD4+ T cells play a central role in protective immunity. In a mouse tumor model, we previously found that tumor growth elicits natural CD4+ T-cell responses, but impedes therapeutic vaccination. We show here that inhibition of vaccine-mediated naïve T-cell priming is due to the presence of a minor but distinct population of tumor-reactive CD4+ T cells. These cells are generated in the tumor draining lymph nodes (LN), are capable of systemic redistribution, and act to limit the representation of antigen-bearing MHC II+ antigen-presenting cells (APC) in contralateral LNs or when transferred to tumor-free mice. Surgical tumor resection, which lowers the representation of tumor primed CD4+ T cells, restored to some extent vaccine-induced CD4+ T-cell activation. Likewise, vaccination with artificial APCs (latex beads) or higher numbers of dendritic cells allowed comparable CD4+ T-cell priming in tumor-free and tumor-bearing mice. Together, our results emphasize the ability of antigen-experienced CD4+ T lymphocytes to interfere with therapeutic vaccination and highlight the need for alternative strategies able to surmount limitations imposed by ongoing immune responses. Cancer Res; 70(15); 6161–70. ©2010 AACR.
A Microfluidic Platform for Systems Pathology: Multiparameter Single-Cell Signaling Measurements of Clinical Brain Tumor Specimens
Authors: Sun Jing , Masterman-Smith Michael D. , Graham Nicholas A. , Jiao Jing , Mottahedeh Jack , Laks Dan R. , Ohashi Minori , DeJesus Jason , Kamei Ken-ichiro , Lee Ki-Bum , Wang Hao , Yu Zeta T.F. , Lu Yi-Tsung , Hou Shuang , Li Keyu , Liu Max , Zhang Nangang , Wang Shutao , Angenieux Brigitte , Panosyan Eduard , Samuels Eric R. , Park Jun , Williams Dirk , Konkankit Vera , Nathanson David , van Dam R. Michael , Phelps Michael E. , Wu Hong , Liau Linda M. , Mischel Paul S. , Lazareff Jorge A. , Kornblum Harley I. , Yong William H. , Graeber Thomas G. , Tseng Hsian-Rong
Published: July 2010

The clinical practice of oncology is being transformed by molecular diagnostics that will enable predictive and personalized medicine. Current technologies for quantitation of the cancer proteome are either qualitative (e.g., immunohistochemistry) or require large sample sizes (e.g., flow cytometry). Here, we report a microfluidic platform—microfluidic image cytometry (MIC)—capable of quantitative, single-cell proteomic analysis of multiple signaling molecules using only 1,000 to 2,800 cells. Using cultured cell lines, we show simultaneous measurement of four critical signaling proteins (EGFR, PTEN, phospho-Akt, and phospho-S6) within the oncogenic phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. To show the clinical application of the MIC platform to solid tumors, we analyzed a panel of 19 human brain tumor biopsies, including glioblastomas. Our MIC measurements were validated by clinical immunohistochemistry and confirmed the striking intertumoral and intratumoral heterogeneity characteristic of glioblastoma. To interpret the multiparameter, single-cell MIC measurements, we adapted bioinformatic methods including self-organizing maps that stratify patients into clusters that predict tumor progression and patient survival. Together with bioinformatic analysis, the MIC platform represents a robust, enabling in vitro molecular diagnostic technology for systems pathology analysis and personalized medicine. Cancer Res; 70(15); 6128–38. ©2010 AACR.
Joint Loss of PAX2 and PTEN Expression in Endometrial Precancers and Cancer
Authors: Monte Nicolas M. , Webster Kaitlyn A. , Neuberg Donna , Dressler Gregory R. , Mutter George L.
Published: July 2010

Latent endometrial carcinoma precancers are normal-appearing endometrial glands with sporadic loss of tumor suppressor gene function such as PTEN. Progression to carcinoma is inefficient and requires additional genetic damage that creates a histologic precursor lesion called endometrial intraepithelial neoplasia (EIN). In this study, we examined loss of PAX2 expression, a gene required for embryonic uterine development, during endometrial carcinogenesis. Normal proliferative, EIN, and malignant (endometrial adenocarcinoma) endometrial tissues were immunostained for PTEN and PAX2. Proliferative samples with loss of protein in at least one gland were scored as latent precancers. EIN and cancer lesions were scored by the majority pattern. Overall prevalence and topography of joint PAX2-PTEN expression loss was examined. The prevalence of PAX2 protein loss in the sequence of normal to precancer to cancer was 36%, 71%, and 77%, respectively, and for PTEN, it was 49%, 44%, and 68%, respectively. The normal endometrial prevalence of PAX2- or PTEN-deficient latent precancers was unaffected by biopsy indication, but increased significantly with age. Coincident loss of PAX2 and PTEN expression in an individual normal endometrium was seen in 21% of patients, but usually involved different glands. Coincident loss was more common in precancers (31%) and carcinoma (55%), in which case, both markers were protein null in an overlapping clonal distribution. PAX2 and PTEN protein loss occurs independently and accumulates with increasing age in latent precancers of normal premenopausal endometrium. Loss of function of both genes in an overlapping distribution characterizes the clinical emergence of a premalignant lesion which is carried forward to carcinoma. Cancer Res; 70(15); 6225–32. ©2010 AACR.
Circadian Rhythm of Transferrin Receptor 1 Gene Expression Controlled by c-Myc in Colon Cancer–Bearing Mice
Authors: Okazaki Fumiyasu , Matsunaga Naoya , Okazaki Hiroyuki , Utoguchi Naoki , Suzuki Ryo , Maruyama Kazuo , Koyanagi Satoru , Ohdo Shigehiro
Published: July 2010

The abundance of cell surface levels of transferrin receptor 1 (TfR1), which regulates the uptake of iron-bound transferring, correlates with the rate of cell proliferation. Because TfR1 expression is higher in cancer cells than in normal cells, it offers a target for cancer therapy. In this study, we found that the expression of TfR1 in mouse colon cancer cells was affected by the circadian organization of the molecular clock. The core circadian oscillator is composed of an autoregulatory transcription-translation feedback loop, in which CLOCK and BMAL1 are positive regulators and the Period (Per), Cryptochrome (Cry), and Dec genes act as negative regulators. TfR1 in colon cancer–bearing mice exhibited a 24-hour rhythm in mRNA and protein levels. Luciferase reporter analysis and chromatin immunoprecipitation experiments suggested that the clock-controlled gene c-MYC rhythmically activated the transcription of the TfR1 gene. Platinum incorporation into tumor DNA and the antitumor efficacy of transferrin-conjugated liposome-delivered oxaliplatin could be enhanced by drug administration at times when TfR1 expression increased. Our findings suggest that the 24-hour rhythm of TfR1 expression may form an important aspect of strategies for TfR1-targeted cancer therapy. Cancer Res; 70(15); 6238–46. ©2010 AACR.
Inhibition of ADP Ribosylation Prevents and Cures Helicobacter-Induced Gastric Preneoplasia
Authors: Toller Isabella M. , Altmeyer Matthias , Kohler Esther , Hottiger Michael O. , Müller Anne
Published: July 2010

Gastric adenocarcinoma develops as a consequence of chronic inflammation of the stomach lining that is caused by persistent infection with the bacterium Helicobacter pylori. Gastric carcinogenesis progresses through a sequence of preneoplastic lesions that manifest histologically as atrophic gastritis, intestinal metaplasia, and dysplasia. We show here in several preclinical models of Helicobacter-induced atrophic gastritis, epithelial hyperplasia, and metaplasia that the inhibition of ADP ribosylation by the small-molecule inhibitor PJ34 not only prevents the formation of gastric cancer precursor lesions, but also efficiently reverses preexisting lesions. PJ34 exerts its chemopreventive and therapeutic effects by impairing Helicobacter-specific T-cell priming and TH1 polarization in the gut-draining mesenteric lymph nodes. The subsequent infiltration of pathogenic T cells into the gastric mucosa and the ensuing gastric T cell–driven immunopathology are prevented efficiently by PJ34. Our data indicate that PJ34 directly suppresses T-cell effector functions by blocking the IFN-γ production of mesenteric lymph node T cells ex vivo. Upon exposure to PJ34, purified T cells failed to synthesize ADP-ribose polymers and to activate the transcription of genes encoding IFN-γ, interleukin 2, and the interleukin 2 receptor α chain in response to stimuli such as CD3/CD28 cross-linking or phorbol 12-myristate 13-acetate/ionomycin. The immunosuppressive and chemoprotective effects of PJ34 therefore result from impaired T-cell activation and TH1 polarization, and lead to the protection from preneoplastic gastric immunopathology. In conclusion, ADP-ribosylating enzymes constitute novel targets for the treatment of Helicobacter-associated gastric lesions predisposing infected individuals to gastric cancer and may also hold promise for the treatment of other T cell–driven chronic inflammatory conditions and autoimmune pathologies. Cancer Res; 70(14); 5912–22. ©2010 AACR.
Advances in Targeting Src in the Treatment of Breast Cancer and Other Solid Malignancies
Authors: Mayer Erica L. , Krop Ian E.
Published: July 2010

Src, a membrane-associated nonreceptor tyrosine kinase, plays a crucial role in the coordination and facilitation of cell-signaling pathways controlling a wide range of cellular functions, including growth, survival, invasion, adhesion, and migration. Deregulation and increased activity of Src has been observed in multiple human malignancies, prompting the development of specific inhibitors of Src. In preclinical studies, Src inhibitors show antitumor effects in multiple solid tumor types. Recently completed early-phase trials using the inhibitors dasatinib and bosutinib have suggested modest activity as monotherapy in breast and prostate cancer, with potentially greater activity in combination regimens. Given the interaction between Src and the estrogen receptor, ongoing trials are exploring combinations with endocrine therapy. The relationship between Src and the vascular endothelial growth factor receptor also justifies investigation of combinations with angiogenesis inhibitors. Future trials will continue to explore the contribution of Src inhibition with both chemotherapy and targeted agents. Clin Cancer Res; 16(14); 3526–32. ©2010 AACR.
Preclinical and Clinical Estimates of the Basal Apoptotic Rate of a Cancer Predict the Amount of Apoptosis Induced by Subsequent Proapoptotic Stimuli
Authors: Zhang Lian , Kavanagh Brian D. , Thorburn Andrew M. , Camidge D. Ross
Published: July 2010

Purpose: We hypothesized that the basal apoptotic rate (BAR) of a cancer would predict sensitivity to subsequent proapoptotic stimuli. To explore this, preclinical and clinical BAR assays were developed measuring cumulative apoptotic events through ELISAs for soluble caspase-cleaved cytokeratin 18 (M30) normalized to either cell number increase or total tumor volume, respectively.

Experimental Design: The BARs of A549, HCC44, and SW1573 non–small cell lung carcinoma cell lines were measured following different pro/antiapoptotic manipulations. In isogenic wild-type and stable knockdown (KD) series, pretreatment BARs were correlated with response to proapoptotic stimuli and compared with established apoptosis assays. Pretreatment and posttreatment serum was available from stereotactic body radiation therapy patients.

Results: Caspase inhibition and p53 KDs reduced the BAR, whereas serum deprivation, XIAP, or Bcl2 KDs increased the BAR. The nontreated BAR rank ordering of the XIAP series recapitulated that with terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and caspase-3/7 activity assays, and predicted each line's sensitivity to TRAIL or irradiation. Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling, however, underestimated basal apoptosis during increased apoptotic stress, and caspase-3/7 activity detected minimal death in the media. P53 KDs with lower nontreated BARs were less sensitive to TRAIL and cisplatinum than wild-type. Stereotactic body radiation therapy increased serum M30 values, and the pretreatment clinical BAR strongly correlated with fold change in M30 on treatment (r = 0.93).

Conclusions: M30-based BAR assays reflect apoptosis accurately and are more amenable to clinical application than existing apoptosis assays. The pretreatment BAR correlates with cell and/or tumor sensitivity to extrinsic and intrinsic apoptotic pathway stimulation. Prospective clinical exploration is warranted. Clin Cancer Res; 16(17); 4478–89. ©2010 AACR.
Some Issues of Japanese Speech-Language-Hearing Therapy Education
Authors: Iitaka Kyoko , Otomo Kiyoshi
Published: July 2010

Recent trends in Japanese speech-language-hearing (SLH) therapy education are reported. The rapid growth of educational institutions has continued since our last report. The educational curriculum was established by the 1997 certification of Japanese SLH therapists, and is strictly applied to educating both college/university and vocational school students. Over 1,000 students annually become registered SLH therapists, of whom nearly 70% are under the age of 39 years. More therapists are employed full time to serve the adult population, while a limited number of therapists are fully employed to provide services to children. As a member of the economically more advanced nations, Japan receives assistance from foreign workers coming from economically less developed nations. Their children face the difficult tasks of learning both their mother tongue and Japanese. There is a strong need for our profession to assist the early language acquisition of these children because their cognitive and personal development will be greatly influenced by adequate language acquisition. An appeal is made to our colleagues for sharing the mutual tasks of bringing about better linguistic and communicative development in those educationally disadvantaged children.
Trends of Home Drug Storage and Use in Different Regions across the Northern United Arab Emirates
Authors: Sharif Suleiman I. , Abduelkarem Abduelmula R. , Bustami Hadeel A. , Haddad Layal I. , Khalil Deema S.
Published: July 2010

Objectives: To investigate the habits of use and home storage of over-the-counter (OTC) and prescription drugs. Subjects and Methods: A pretested questionnaire was distributed to university students who represented 300 household units in different regions of the northern United Arab Emirates. Household chairs (parents) answered questions on various aspects of home use and storage of OTC and prescription medicines. The number of drugs stored at home was collapsed into 5 unequal groups (1–3, 4–6, 7–10, 11–15 and 16–20). Results: The response rate was 300 (100%). The average number of drugs per household unit was 6 items. Almost 40% of the participants stored between 16 and 20 drugs. More than half (56%) of the household units stored medicines in a home pharmacy kept either in the bedroom (n = 66; 39%) or in the kitchen (n = 71; 42%). No correlation was found between the level of education and the number of family members (r = 0.29) or drugs stored at home (r = –0.35). Only 2 (0.7%) of the participants did not keep drugs at home. There was a clear discrepancy in either OTC or prescription drugs stored, and the variation in the utilization and preference of drugs was obvious among the pooled sample. Conclusion: Various problems related to the use and storage at home of OTC and prescription drugs were revealed. Discussing the results of this survey with students who participated as members of the household units that took part in the study may prove to be a helpful intervention. The need for public educational efforts on the rational use of medicines at home is urgent to foster awareness of the proper use of drugs.
Health Care Utilization among Chronic Obstructive Pulmonary Disease Patients and the Effect of Pulmonary Rehabilitation
Authors: Al Moamary Mohamed S.
Published: July 2010

Objective: The present study aimed to analyze the utilization of health care resources among patients with chronic obstructive pulmonary disease (COPD) and to evaluate the effect of adherence to a pulmonary rehabilitation (PR) program on the utilization of these resources. Subjects and Methods: A retrospective review of medical charts of a group of patients with COPD who were enrolled in a standard outpatient PR program at a tertiary care teaching hospital was conducted. Eligible patients were above the age of 18 years with a history of dyspnea, chronic cough and/or exposure to a disease risk factor with a postbronchodilator FEV1/FVC ratio <0.7. Results: Fifty patients were referred to the PR program. The average number of emergency department visits was 1.4 ± 1.6 days, the length of stay in the hospital was 1.7 ± 3.8 days, the pulmonary clinic scheduled visits were 3.9 ± 2.2, the use of combined inhalers was 9.0 ± 3.9 canisters, the use of short-acting bronchodilator was 9.0 ± 5.6 canisters, the cumulative prednisone doses were 427.5 ± 463 mg, and the use of antibiotic courses was 3.1 ± 2.9. Of the referred patients, 27 (54%) were adherent and 23 (46%) were not. Except for the use of combined inhalers, all parameters were significantly reduced in the adherent group. In contrast, the nonadherent group had increases in use of prednisone and antibiotics (p < 0.05). Conclusion: There was a reduction in the utilization of health care resources among adherent patients with COPD who completed a PR program as reflected in selected pharmacological and nonpharmacological parameters.
Self-Medication among Healthcare and Non-Healthcare Students at University of Ljubljana, Slovenia
Authors: Klemenc-Ketis Zalika , Hladnik Ziga , Kersnik Janko
Published: July 2010

Objective: To determine the incidence of self-medication among University of Ljubljana students and the effect of the type of curriculum on the pattern of self-medication. Subjects and Methods: The study included a sample of 1,294 students who freely accessed a self-administered web-based questionnaire in the Slovene language that consisted of a preliminary letter introducing the term ‘self-treatment’ and 2 sections about self-medication. The preliminary letter asked participants to report the practice of self-treatment during the past year. The main outcome measures were percentages of those reporting self-medication during the past year, which were then used to compare healthcare and non-healthcare students. Results: A majority of students (1,195, 92.3%), both healthcare and non-healthcare, reported the use of some sort of self-medication during the study period. More healthcare students in their senior year (353, 94.1%) than those in their junior year (245, 89.4%) used self-medication (p = 0.04). Healthcare students (p = 0.05) thought that self-medication without improvement of the symptoms should last for 1 week or less. They acquired the drugs for self-medication from pharmacies; thought that previous doctors’ advice in a similar situation was a more important reason for self-medication; would seek the advice of a physician or pharmacist for different ways of self-treatment, and quite interestingly thought that self-medication was not very safe. On the other hand, non-healthcare students acquired the drugs from healers and friends. Conclusion: The study showed that self-medication was common among all University of Ljubljana students, but that healthcare-related education in students and young adults led to more responsible use of self-medication.
Context Representation and Thought Disorder in Schizophrenia
Authors: Roesch-Ely Daniela , Spitzer Manfred , Kaiser Stefan , Weisbrod Matthias , Pfueller Ute
Published: July 2010

Background: Formal thought disorder (FTD) in schizophrenia is related to a disturbance in the representation of contextual information. This study aimed to assess the extent to which the ‘context module’ is disturbed in patients with schizophrenia. The context module is needed to mediate an appropriate behavioral response. It comprises 2 cognitive functions, namely working memory and behavioral inhibition, and is linked to networks in the prefrontal cortex. We compared patients with enhanced FTD (n = 15) to ones with low levels and a control group (n = 21, respectively). We hypothesized that FTD patients would have greater degradation of the context module by presenting both working memory and inhibition deficits, while in low FTD patients mild degradation of the context module would be present with working memory deficits only. Methods: Using a within-subjects design, subjects underwent a battery of neuropsychological tests with different demands on the context module. We also divided patients according to first-episode versus chronic course. Results: Our results confirmed our predictions on FTD. However, first-episode patients showed working memory deficits more than those with several episodes. Conclusion: We conclude that the context module is more degraded in FTD patients, although our results have to be interpreted with caution because of the small sample size.
The Canon: Learning through the Life Stages
Authors: Rochester Kathleen
Published: July 2010

The varied content and styles of the Torah, Prophets and Writings provide a rich range of resources for preaching, teaching and learning. Each is appropriate for different stages of our faith journeys.
Effects of occupational lead exposure on renal and nervous system of workers of traditional tile factories in Mashhad (northeast of Iran)
Authors: Habibollah Nemati Karimooy  , Mahdi Balali Mood  , Hosseini Mahmoud , Shadmanfar Sedigheh
Published: July 2010

Occupational lead poisoning is a health problem in Iran. Renal and neuropsychiatric complications of occupational lead poisoning are the main concerns for the workers and their employers. It was thus aimed to investigate the renal and neurotoxic effects of lead poisoning in the workers of two traditional-tile-factories. Researchers visited the workers in the factories and collected data by taking direct history and physical examinations in summer of 2005. Data were recorded in previously designed forms. Blood and urine lead concentrations were measured by an atomic absorption technique. A neurologist examined all workers and electrophysiological investigations were undertaken as clinically indicated. Data were analyzed by SPSS software and chi-square, student t test and Pearson correlation tests were used accordingly. The numerical data were expressed as mean ± standard deviation and p < 0.05 was considered as the significant level. Overall, 108 male subjects aged 37 ± 7.8 years were studied. Duration of lead exposure was 9.8 ± 6 years. Lead concentration in 2005 was 361.5 ± 176.9 μg/L. The main objective clinical findings were lead line (64.8%), peripheral neuropathy of upper limb (37%), suppression of deep tendon reflexes (DTR) in upper limbs (25.7%), tremor (23.3%), peripheral neuropathy of lower limbs (17%) and abdominal tenderness (15.1%). The subjective findings were mainly on the central nervous system, such as loss of memory (57%), moodiness (56.1%), agitation (47.7%), drowsiness (36.4%), and headache (29.9%). There was no significant correlation between blood lead concentration and glomerular filtration rate (GFR). But there were significant correlations between the blood lead concentrations and urine lead concentration (p < 0.001). This study showed that lead had toxic effects on the teeth (bone), central and peripheral nervous system, more than renal function. Prophylactic and treatment measures were performed.
Mediating and Moderating Effects of Differentiation of Self on Depression Symptomatology in a Rural Community Sample
Authors: Hooper Lisa M. , DePuy Venita
Published: July 2010

Differentiation of self—a core construct of Bowen’s family systems theory, which represents psychological health and healthy functioning—was examined as a possible predictor of depression and as a mediator and moderator of the relation between family conflict (F-CON) and depression symptomatology (DEP). A total of 60 racially diverse adults (M = 41.20, SD = 8.53) from a rural community participated. All data were obtained from standardized self-report questionnaires measuring family variables (F-CON and differentiation of self) and psychological outcome (DEP). F-CON and differentiation of self were correlated with and predictive of DEP. A multivariate, multiple regression model revealed that differentiation of self partially mediated the effects of F-CON on DEP. However, results from a hierarchical regression model showed that differentiation of self did not moderate the relation between F-CON and DEP. Taken together, these preliminary findings provide evidence of the importance of the associations between family systemic factors (F-CON and differentiation of self) and DEP. Implications and directions for future research and family counseling are put forward.
Preventive Health Care Practices of Former Soviet Union Immigrant Women in Germany and the United States
Authors: Ivanov L. Louise , Jie Hu  , Pokhis Karina , Roth Wolfgang
Published: July 2010

Objectives: To examine the use of preventive health care practices of mammography, Pap smear, and breast self-exam in immigrant women from the former Soviet Union in Germany and the United States. Design: A descriptive cross-sectional exploratory study was used to examine the preventive health care practices of immigrant women in Germany and the United States. Sample: A convenience sample of 15 German immigrant women from the former Soviet Union were solicited from the Salztal Klinik in Germany and matched by age with 24 U.S. immigrant women from the former Soviet Union solicited from a community center for immigrants. Measurements: Data were collected using a demographic survey and the Language, Identity, and Behavior Acculturation Measure. Results: Significant differences were found between the German and U.S. immigrant groups in use of mammography (χ2 = 8.069, df = 1, p < .005) and Pap smear (χ2 = 7.245, df = 1, p < .008). Conclusion: The low use of mammography and Pap smear among German immigrant women may be related to differences in health care systems, age, and health beliefs. Further study is needed to determine the affects of age and health beliefs related to health promotion and disease prevention to better understand how to intervene and improve the health of immigrant women from the former Soviet Union.
Redistribution at the State and Local Level: Consequences for Economic Growth
Authors: Chernick Howard
Published: July 2010

Fiscal redistribution varies substantially across U.S. states, both on the tax and spending side. A compensating differential framework is used to show that greater redistribution will tend to increase the gross wage of skilled workers but that any increase could be offset by stronger preferences for redistribution. An increase in gross wages raises the cost of output in the more redistributive state, leading to a predicted decline in income and output. To test the model, five- and ten-year per capita and aggregate growth rates are estimated as a function of initial measures of tax and expenditure incidence. Data are a four-period panel of U.S. states from 1977 to 1995. Tax progressivity is measured both overall and for the income tax alone. Expenditure progressivity is measured by spending on welfare and higher education, and the state share of elementary and secondary education spending. Tax structure and welfare spending are instrumented. State tax progressivity shows no effect on growth. Welfare spending has a negative effect on aggregate income growth but not on per capita income. Higher education spending is unrelated to growth. Fiscal spillovers within regions are asymmetric. Progressive taxation and more higher education spending by a state’s geographic neighbors have positive effects on own-state growth. The asymmetry in tax effects explains why interstate tax competition does not lead to geographic convergence in fiscal structures. The results suggest that interstate differences in fiscal redistribution are welfare enhancing in the Pareto sense.
Safety Evaluation of Zinc Threoninate Chelate
Authors: Hu Xiao-bo , Gong Yi , Li Lei , Nie Shao-ping , Wang Yuan-xing , Xie Ming-yong
Published: July 2010

The acute toxicity of zinc threoninate chelate was assessed. The oral lethal dose 50% (LD50) was 2710 mg/kg in female rats and 3160 mg/kg in male rats. Genotoxicity was assessed by Ames test in Salmonella typhimurium strains TA97, TA98, TA100, and TA102, by bone marrow mouse micronucleus test and a sperm abnormality test with mice. Thirty-day repeat dose toxicity study was conducted at oral daily doses of 0, 42, 169, and 675 mg/kg in rats. Teratogenicity was assessed at the same daily dose in pregnant rats by gavage. No significant changes in body weight, food consumption, organ weight, relative organ weight, hematology, blood biochemistry, histopathology, behavior, mortality, sperm abnormality, mutagenicity, and micronucleus formation were observed and no clinical signs or adverse effects were detected. Zinc threoninate chelate had no significant teratogenic effect at a daily dose of 42 mg/kg.
The Use of Ethnography and Narrative Interviews in a Study of ‘Cultures of Dance’
Authors: Paulson Susan
Published: July 2010

In this study I used both ethnography and narrative interviews rather than narrative interviews alone to explore ‘cultures of dance’. Ethnography provides greater ecological validity because the researcher has the opportunity to participate in the various cultures from which interviewees are recruited. The processes of social transformation can be observed and documented, and how the culture becomes embodied in individual participants in material terms, alongside the recording of their narratives. It is more labour-intensive to set up and sustain an ethnographic study, but combining ethnography with narrative interviews produces deeper findings than a purely qualitative interview study.
Heeding the Push from Below
Authors: Campbell Catherine , Cornish Flora , Gibbs Andrew , Scott Kerry
Published: July 2010

This article discusses three successful pro-poor social movements: the Brazilian Landless Workers’ Movement, the Indian wing of the People’s Health Movement and the South African Treatment Action Campaign. These have mobilized poor people to demand access to land, health services and life-saving medical treatment respectively. We show how each group has succeeded not only through building the ‘voice’ of the poor to make forceful demands, but also through facilitating the development of ‘receptive social environments’ in which the rich are willing to take these voices seriously. Community psychologists need to pay more attention to the latter challenge.
A mobile phone: mobility, materiality and everyday Swahili trading practices
Authors: Pfaff Julia
Published: July 2010

This article engages with the recent literature on material culture, ‘follow-the-thing geographies’, mobility and mobile communication technologies by linking these theoretical reflections to ethnographic research in East Africa. Using the biography of a specific mobile phone as a window through which to shed light on the spatial and cultural practices in which the object is embedded, it attempts to provide an insight into contemporary trading practices in a Swahili context. Presenting phases in the life course of a particular mobile phone, it examines different ways of relating to, using, disposing of and acquiring mobile phones, illustrating how a phone is being appropriated and incorporated into the ways of life of many Swahili people and plays an important role in processes of identification. While, on the one hand, grounding the often very generalized discussions of mobile phone use in Africa in the biography of a specific object, on the other hand, the article tries to link its mobility to larger questions of cultural identity and meaning by showing how these are constantly being negotiated and practiced in everyday trading practices.
Geoffrey Fisk and a Hitherto Unknown Contribution to the Treatment of Carpal Instability
Authors: Burke F.D. , Heras-Palou C.
Published: July 2010

We describe two films made by Geoffrey Fisk in 1973 that record midcarpal instability and its surgical treatment.
Role of synectin in lymphatic development in zebrafish and frogs
Authors: Hermans Karlien , Claes Filip , Vandevelde Wouter , Zheng Wei , Geudens Ilse , Orsenigo Fabrizio , De Smet Frederik , Gjini Evisa , Anthonis Kristof , Ren Bin , Kerjaschki Dontcho , Autiero Monica , Ny Annelii , Simons Michael , Dewerchin Mieke , Schulte-Merker Stefan , Dejana Elisabetta , Alitalo Kari , Carmeliet Peter
Published: July 2010

The molecular basis of lymphangiogenesis remains incompletely characterized. Here, we document a novel role for the PDZ domain-containing scaffold protein synectin in lymphangiogenesis using genetic studies in zebrafish and tadpoles. In zebrafish, the thoracic duct arises from parachordal lymphangioblast cells, which in turn derive from secondary lymphangiogenic sprouts from the posterior cardinal vein. Morpholino knockdown of synectin in zebrafish impaired formation of the thoracic duct, due to selective defects in lymphangiogenic but not angiogenic sprouting. Synectin genetically interacted with Vegfr3 and neuropilin-2a in regulating lymphangiogenesis. Silencing of synectin in tadpoles caused lymphatic defects due to an underdevelopment and impaired migration of Prox-1+ lymphatic endothelial cells. Molecular analysis further revealed that synectin regulated Sox18-induced expression of Prox-1 and vascular endothelial growth factor C–induced migration of lymphatic endothelial cells in vitro. These findings reveal a novel role for synectin in lymphatic development.
Novel biomarkers predict liver fibrosis in hepatitis C patients: alpha 2 macroglobulin, vitamin D binding protein and apolipoprotein AI
Authors: Ho Ai-Sheng , Cheng Chun-Chia , Lee Shui-Cheng , Liu Meng-Lun , Lee Jing-Ying , Wang Wen-Ming , Wang Chia-Chi
Published: July 2010

Background

The gold standard of assessing liver fibrosis is liver biopsy, which is invasive and not without risk. Therefore, searching for noninvasive serologic biomarkers for liver fibrosis is an importantly clinical issue.

Methods

A total of 16 healthy volunteers and 45 patients with chronic hepatitis C virus (HCV) were enrolled (F0: n = 16, F1: n = 7, F2: n = 17, F3: n = 8 and F4: n = 13, according to the METAVIR classification). Three serum samples of each fibrotic stage were analyzed by two-dimension difference gel electrophoresis (2D-DIGE). The differential proteins were identified by the cooperation of MALDI-TOF/TOF and MASCOT; then western blotting and Bio-Plex Suspension Array were used to quantify the protein levels.

Results

Three prominent candidate biomarkers were identified: alpha 2 macroglobulin (A2M) is up regulated; vitamin D binding protein (VDBP) and apolipoprotein AI (ApoAI) are down regulated. The serum concentration of A2M was significantly different among normal, mild (F1/F2) and advanced fibrosis (F3/F4) (p < 0.01). The protein levels of VDBP and ApoAI were significantly higher in normal/mild fibrosis, when compared to those in advanced fibrosis (both p < 0.01).

Conclusions

This study not only reveals three putative biomarkers of liver fibrosis (A2M, VDBP and ApoAI) but also proves the differential expressions of those markers in different stages of fibrosis. We expect that combination of these novel biomarkers could be applied clinically to predict the stage of liver fibrosis without the need of liver biopsy.
Peripheral blood T Regulatory cell counts may not predict transplant rejection
Authors: Huang Yuchuan , Shan Juan , Zhang Chuntao , Zhang Jie , Feng Li , Li Shengfu , Li Youping
Published: July 2010

Background

Recent evidence shows that allograft survival rates show a positive correlation with the number of circulating T regulatory cells (Tregs). This study investigated both the number and the cytokine profiles exhibited by Foxp3+ Tregs in blood, spleen and lymph nodes of Lewis rat recipients of BN rat cardiac allografts after a single-dose of Rapamycin (RAPA).

Results

Rats were divided into three groups: control group (containing healthy control and acute rejection group), and recipients treated with a single dose of RAPA on either Day 1 (1D group)or Day 3 (3D group) post-transplant. We analyzed the number of Foxp3+Tregs and the expression of Foxp3 and cytokines in the peripheral blood and the peripheral lymphoid tissues. No difference was found in the numbers of circulating Foxp3+ Tregs between these three groups. RAPA administration significantly increased Foxp3 expression in peripheral lymphoid tissues after a single dose of RAPA on Day 3 post-transplant. Foxp3+Tregs inhibited the activity of effector T cells (Teff) via the secretion of TGF-β1.

Conclusion

The number of Tregs in the recipient's blood may not be a good predictor of transplant rejection. Foxp3+Tregs inhibit the activity of Teff cells mainly in the peripheral lymphoid tissues.