Integrating a Patient Care Development Model to Enhance Community Pharmacy Residency Programs

Purpose: The purpose of this paper is to describe integration of a community-based patient care service development model, Partner for Promotion (PFP), within five community pharmacy residency programs (CPRPs) across the United States and provide insights and examples of methods for optimizing community pharmacy resident experiences, developing new patient care services, and achieving residency accreditation standards. Summary: Five community pharmacy residency programs have integrated PFP that affiliated with Midwestern University – Glendale, Northeast Ohio Medical University, Ohio State University, University of Utah, and West Virginia University. Each college and residency program has identified different strategies through which PFP enhances their residency training and service development including completion of training modules, reflections and discussion on application of the PFP service development model to practice, research, and teaching, use of assignments to guide service creation, and mentoring of PFP student-pharmacist teams. All five sites directly link these activities to objectives required in PGY1 CPRP accreditation standards. PFP has resulted in resident-facilitated service development of a variety of patient care programs. Conclusion: PFP applied to CPRPs enhances training on service development, builds new services within residency training sites, and assists programs with meeting residency accreditation standards. The experiences of five community pharmacy residency programs across the U.S. that have adopted the program has been positive, with creation of new services and residency sites, integration of novel teaching, practice, research, and learning opportunities for residents, and direct links from the PFP experience to achievement of residency objectives.   Type: Idea Pape

Hyperfine structure of the ground state muonic He-3 atom

On the basis of the perturbation theory in the fine structure constant $\alpha$ and the ratio of the electron to muon masses we calculate one-loop vacuum polarization and electron vertex corrections and the nuclear structure corrections to the hyperfine splitting of the ground state of muonic helium atom $(\mu\ e \ ^3_2He)$. We obtain total result for the ground state hyperfine splitting $\Delta \nu^{hfs}=4166.471$ MHz which improves the previous calculation of Lakdawala and Mohr due to the account of new corrections of orders $\alpha^5$ and $\alpha^6$. The remaining difference between our theoretical result and experimental value of the hyperfine splitting lies in the range of theoretical and experimental errors and requires the subsequent investigation of higher order corrections.Comment: Talk on poster section of XXIV spectroscopy congress, 28 February-5 March 2010, Moscow-Troitsk, Russia, 21 pages, LaTeX, 8 figure

Inhibition of StearoylCoA Desaturase Activity Blocks Cell Cycle Progression and Induces Programmed Cell Death in Lung Cancer Cells

Lung cancer is the most frequent form of cancer. The survival rate for patients with metastatic lung cancer is ∼5%, hence alternative therapeutic strategies to treat this disease are critically needed. Recent studies suggest that lipid biosynthetic pathways, particularly fatty acid synthesis and desaturation, are promising molecular targets for cancer therapy. We have previously reported that inhibition of stearoylCoA desaturase-1 (SCD1), the enzyme that produces monounsaturated fatty acids (MUFA), impairs lung cancer cell proliferation, survival and invasiveness, and dramatically reduces tumor formation in mice. In this report, we show that inhibition of SCD activity in human lung cancer cells with the small molecule SCD inhibitor CVT-11127 reduced lipid synthesis and impaired proliferation by blocking the progression of cell cycle through the G1/S boundary and by triggering programmed cell death. These alterations resulting from SCD blockade were fully reversed by either oleic (18:1n-9), palmitoleic acid (16:1n-7) or cis-vaccenic acid (18:1n-7) demonstrating that cis-MUFA are key molecules for cancer cell proliferation. Additionally, co-treatment of cells with CVT-11127 and CP-640186, a specific acetylCoA carboxylase (ACC) inhibitor, did not potentiate the growth inhibitory effect of these compounds, suggesting that inhibition of ACC or SCD1 affects a similar target critical for cell proliferation, likely MUFA, the common fatty acid product in the pathway. This hypothesis was further reinforced by the observation that exogenous oleic acid reverses the anti-growth effect of SCD and ACC inhibitors. Finally, exogenous oleic acid restored the globally decreased levels of cell lipids in cells undergoing a blockade of SCD activity, indicating that active lipid synthesis is required for the fatty acid-mediated restoration of proliferation in SCD1-inhibited cells. Altogether, these observations suggest that SCD1 controls cell cycle progression and apoptosis and, consequently, the overall rate of proliferation in cancer cells through MUFA-mediated activation of lipid synthesis

PINCH is an independent prognostic factor in rectal cancer patients without preoperative radiotherapy - a study in a Swedish rectal cancer trial of preoperative radiotherapy

<p>Abstract</p> <p>Background</p> <p>The clinical significance between particularly interesting new cysteine-histidine rich protein (PINCH) expression and radiotherapy (RT) in tumours is not known. In this study, the expression of PINCH and its relationship to RT, clinical, pathological and biological factors were studied in rectal cancer patients.</p> <p>Methods</p> <p>PINCH expression determined by immunohistochemistry was analysed at the invasive margin and inner tumour area in 137 primary rectal adenocarcinomas (72 cases without RT and 65 cases with RT). PINCH expression in colon fibroblast cell line (CCD-18 Co) was determined by western blot.</p> <p>Results</p> <p>In patients without RT, strong PINCH expression at the invasive margin of primary tumours was related to worse survival, compared to patients with weak expression, independent of TNM stage and differentiation (<it>P </it>= 0.03). No survival relationship in patients with RT was observed (<it>P </it>= 0.64). Comparing the non-RT with RT subgroup, there was no difference in PINCH expression in primary tumours (invasive margin (<it>P </it>= 0.68)/inner tumour area (<it>P </it>= 0.49). In patients with RT, strong PINCH expression was related to a higher grade of LVD (lymphatic vessel density) (<it>P </it>= 0.01)</p> <p>Conclusions</p> <p>PINCH expression at the invasive margin was an independent prognostic factor in patients without RT. RT does not seem to directly affect the PINCH expression.</p

Different fatty acid metabolism effects of (−)-epigallocatechin-3-gallate and C75 in adenocarcinoma lung cancer

Background Fatty acid synthase (FASN) is overexpressed and hyperactivated in several human carcinomas, including lung cancer. We characterize and compare the anti-cancer effects of the FASN inhibitors C75 and (−)-epigallocatechin-3-gallate (EGCG) in a lung cancer model. Methods We evaluated in vitro the effects of C75 and EGCG on fatty acid metabolism (FASN and CPT enzymes), cellular proliferation, apoptosis and cell signaling (EGFR, ERK1/2, AKT and mTOR) in human A549 lung carcinoma cells. In vivo, we evaluated their anti-tumour activity and their effect on body weight in a mice model of human adenocarcinoma xenograft. Results C75 and EGCG had comparable effects in blocking FASN activity (96,9% and 89,3% of inhibition, respectively). In contrast, EGCG had either no significant effect in CPT activity, the rate-limiting enzyme of fatty acid β-oxidation, while C75 stimulated CPT up to 130%. Treating lung cancer cells with EGCG or C75 induced apoptosis and affected EGFR-signaling. While EGCG abolished p-EGFR, p-AKT, p-ERK1/2 and p-mTOR, C75 was less active in decreasing the levels of EGFR and p-AKT. In vivo, EGCG and C75 blocked the growth of lung cancer xenografts but C75 treatment, not EGCG, caused a marked animal weight loss. Conclusions In lung cancer, inhibition of FASN using EGCG can be achieved without parallel stimulation of fatty acid oxidation and this effect is related mainly to EGFR signaling pathway. EGCG reduce the growth of adenocarcinoma human lung cancer xenografts without inducing body weight loss. Taken together, EGCG may be a candidate for future pre-clinical development

Meta-analysis of diffusion tensor imaging studies shows altered fractional anisotropy occurring in distinct brain areas in association with depression

Fractional anisotropy anomalies occurring in the white matter tracts in the brains of depressed patients may reflect microstructural changes underlying the pathophysiology of this disorder. We conducted a meta-analysis of fractional anisotropy abnormalities occurring in major depressive disorder using voxel-based diffusion tensor imaging studies. Using the Embase, PubMed and Google Scholar databases, 89 relevant data sets were identified, of which 7 (including 188 patients with major depressive disorder and 221 healthy controls) met our inclusion criteria. Authors were contacted to retrieve any additional data required. Coordinates were extracted from clusters of significant white matter fractional anisotropy differences between patients and controls. Relevant demographic, clinical and methodological variables were extracted from each study or obtained directly from authors. The meta-analysis was carried out using Signed Differential Mapping. Patients with depression showed decreased white matter fractional anisotropy values in the superior longitudinal fasciculus and increased fractional anisotropy values in the fronto-occipital fasciculus compared to controls. Using quartile and jackknife sensitivity analysis, we found that reduced fractional anisotropy in the left superior longitudinal fasciculus was very stable, with increases in the right fronto-occipital fasciculus driven by just one study. In conclusion, our meta-analysis revealed a significant reduction in fractional anisotropy values in the left superior longitudinal fasciculus, which may ultimately play an important role in the pathology of depression

The Role of UPF0157 in the Folding of M. tuberculosis Dephosphocoenzyme A Kinase and the Regulation of the Latter by CTP

BACKGROUND:Targeting the biosynthetic pathway of Coenzyme A (CoA) for drug development will compromise multiple cellular functions of the tubercular pathogen simultaneously. Structural divergence in the organization of the penultimate and final enzymes of CoA biosynthesis in the host and pathogen and the differences in their regulation mark out the final enzyme, dephosphocoenzyme A kinase (CoaE) as a potential drug target. METHODOLOGY/PRINCIPAL FINDINGS:We report here a complete biochemical and biophysical characterization of the M. tuberculosis CoaE, an enzyme essential for the pathogen's survival, elucidating for the first time the interactions of a dephosphocoenzyme A kinase with its substrates, dephosphocoenzyme A and ATP; its product, CoA and an intrinsic yet novel inhibitor, CTP, which helps modulate the enzyme's kinetic capabilities providing interesting insights into the regulation of CoaE activity. We show that the mycobacterial enzyme is almost 21 times more catalytically proficient than its counterparts in other prokaryotes. ITC measurements illustrate that the enzyme follows an ordered mechanism of substrate addition with DCoA as the leading substrate and ATP following in tow. Kinetic and ITC experiments demonstrate that though CTP binds strongly to the enzyme, it is unable to participate in DCoA phosphorylation. We report that CTP actually inhibits the enzyme by decreasing its Vmax. Not surprisingly, a structural homology search for the modeled mycobacterial CoaE picks up cytidylmonophosphate kinases, deoxycytidine kinases, and cytidylate kinases as close homologs. Docking of DCoA and CTP to CoaE shows that both ligands bind at the same site, their interactions being stabilized by 26 and 28 hydrogen bonds respectively. We have also assigned a role for the universal Unknown Protein Family 0157 (UPF0157) domain in the mycobacterial CoaE in the proper folding of the full length enzyme. CONCLUSIONS/SIGNIFICANCE:In view of the evidence presented, it is imperative to assign a greater role to the last enzyme of Coenzyme A biosynthesis in metabolite flow regulation through this critical biosynthetic pathway

Translation and validation study of the Persian version of the Arthritis Impact Measurement Scales 2 (AIMS2) in patients with osteoarthritis of the knee

Background: The Arthritis Impact Measurement Scales 2 (AIMS2) has not been translated and validated for Persian-speaking patients with osteoarthritis of the knee. This was to provide a validated instrument to measure functional disability and health-related quality of life in patients with osteoarthritis of the knee in Iran. The aim of this study was to culturally adapt and validate the AIMS2 for Persian-speaking patients with osteoarthritis of the knee in Iran. Methods: A consecutive sample of patients with knee osteoarthritis were asked to complete the AIMS2, the Short Form Health Survey (SF-36) and four visual analog scales for pain, joint stiffness, patient's and physician's global assessment. Internal consistency and convergent validity were applied to examine psychometric properties of the AIMS2. In addition, 30 randomly selected patients were asked to complete the questionnaire two days later for the second time for test-retest reliability. Finally factor structure of the Persian AIMS2 was performed using the principal component factor analysis. Results: In all 230 patients were entered into the study. The mean (SD) age of the participants was 56.9 (8.7) years and the mean (SD) duration of disease was 7.2 (3.5) years. Cronbach's alpha coefficient and intraclass correlation coefficient (ICC) for the Persian AIMS2 scales ranged from 0.74 to 0.92 and 0.85 to 0.96, respectively. The correlation between most of the Persian AIMS2 scales and the physical and mental summary scores of the SF-36 and the visual analogue scales for pain, joint stiffness, patient's and physician's global assessment were statistically significant indicating a good convergent validity (p < 0.05). The results obtained from factor analysis indicated three latent factors that jointly accounted for 67.5% of the total variance. Conclusion: The results showed that the Persian AIMS2 had reasonably good internal consistency, test-retest reliability, and convergent validity in patients with osteoarthritis of the knee. It is simple and easy to use and now can be applied in the future studies in Iran. However, its sensitivity to change needs still to be studied.We wish to express our gratitude to physicians who co-operated in the selection of the patients and patients who gave their time to complete the questionnaires. This research was supported by Sport Medicine Research Center (SMRC), Tehran University of Medical Sciences; grant No 85-01-53-3579

The Whereabouts of 2D Gels in Quantitative Proteomics

Two-dimensional gel electrophoresis has been instrumental in the development of proteomics. Although it is no longer the exclusive scheme used for proteomics, its unique features make it a still highly valuable tool, especially when multiple quantitative comparisons of samples must be made, and even for large samples series. However, quantitative proteomics using 2D gels is critically dependent on the performances of the protein detection methods used after the electrophoretic separations. This chapter therefore examines critically the various detection methods (radioactivity, dyes, fluorescence, and silver) as well as the data analysis issues that must be taken into account when quantitative comparative analysis of 2D gels is performed