169 research outputs found

    One-loop quantum cosmological correction to the gravitational constant using the kink solution in de Sitter universe

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    In this paper, we show the equivalence between a classical static scalar field theory and the (closed) de Sitter cosmological model whose potential represents shape invariance property. Based on this equivalence, we calculate the one-loop quantum cosmological correction to the ground state energy of the kink-like solution in the (closed) de Sitter cosmological model in which the fluctuation potential VV^{\prime\prime} has a shape invariance property. It is shown that this type of correction, which yields a renormalized mass in the case of scalar field theory, may be {\it interpreted} as a renormalized gravitational constant in the case of (closed) de Sitter cosmological model. Keywords: One-loop correction; kink energy; shape invariance; zeta function regularization; de Sitter universe.Comment: 18 page

    A MCP1 fusokine with CCR2-specific tumoricidal activity

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    <p>Abstract</p> <p>Background</p> <p>The CCL2 chemokine is involved in promoting cancer angiogenesis, proliferation and metastasis by malignancies that express CCR2 receptor. Thus the CCL2/CCR2 axis is an attractive molecular target for anticancer drug development.</p> <p>Methods</p> <p>We have generated a novel fusion protein using GMCSF and an N-terminal truncated version of MCP1/CCL2 (6-76) [hereafter GMME1] and investigated its utility as a CCR2-specific tumoricidal agent.</p> <p>Results</p> <p>We found that distinct to full length CCL2 or its N-truncated derivative (CCL2 5-76), GMME1 bound to CCR2 on mouse lymphoma EG7, human multiple myeloma cell line U266, or murine and human medulloblastoma cell lines, and led to their death by apoptosis. We demonstrated that GMME1 specifically blocked CCR2-associated STAT3 phosphorylation and up-regulated pro-apoptotic BAX. Furthermore, GMME1 significantly inhibited EG7 tumor growth in C57BL/6 mice, and induced apoptosis of primary myeloma cells from patients.</p> <p>Conclusion</p> <p>Our data demonstrate that GMME1 is a fusokine with a potent, CCR2 receptor-mediated pro-apoptotic effect on tumor cells and could be exploited as a novel biological therapy for CCR2<sup>+ </sup>malignancies including lymphoid and central nervous system malignancies.</p

    Extra-human epidemiology of Acinetobacter baumannii in Lebanon

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    Presence of Acinetobacter baumannii outside hospitals is still a controversial issue. The objective of our study was to explore the extra hospital epidemiology of A. baumannii in Lebanon. From February 2012 to October 2013, a total of 73 water samples, 51 soil samples, 37 raw cow milk samples, 50 cow meat samples, 7 raw cheese samples and 379 animal samples were analysed by cultural methods for the presence of A. baumannii. Species identification was performed by rpoB gene sequencing. Antibiotic susceptibility was investigated and A. baumannii population was studied by two genotyping approaches: Multilocus Sequence Typing (MLST) and blaOXA-51 Sequence-Based Typing (blaOXA-51 SBT). A. baumannii was detected in 6.9% of water samples, 2.7% of milk samples, 8.0% of meat samples, 14.3% of cheese samples and 7.7% of animal samples. All isolates showed a susceptible phenotype against most of the antibiotics tested and lacked carbapenemase encoding genes except one that harboured a blaOXA-143 gene. MLST analysis revealed the presence of 36 sequence types (ST), among them 24 were novel ST(s), reported for the first time in this study. blaOXA-51 SBT showed the presence of 34 variants, among them 21 were novel and all isolated from animal origin. Finally, 30 isolates had new partial rpoB sequences and were considered as putative new Acinetobacter species. In conclusion, animals can be a potential reservoir for A. baumannii and the dissemination of new emerging carbapenemases. The role of novel identified animal clones in community-acquired infections should be investigated

    Neuroscience-informed classification of prevention interventions in substance use disorders : an RDoC-based approach

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    Neuroscience has contributed to uncover the mechanisms underpinning substance use disorders (SUD). The next frontier is to leverage these mechanisms as active targets to create more effective interventions for SUD treatment and prevention. Recent large-scale cohort studies from early childhood are generating multiple levels of neuroscience-based information with the potential to inform the development and refinement of future preventive strategies. However, there are still no available well-recognized frameworks to guide the integration of these multi-level datasets into prevention interventions. The Research Domain Criteria (RDoC) provides a neuroscience-based multi-system framework that is well suited to facilitate translation of neurobiological mechanisms into behavioral domains amenable to preventative interventions. We propose a novel RDoC-based framework for prevention science and adapted the framework for the existing preventive interventions. From a systematic review of randomized controlled trials using a person-centered drug/alcohol preventive approach for adolescents, we identified 22 unique preventive interventions. By teasing apart these 22 interventions into the RDoC domains, we proposed distinct neurocognitive trajectories which have been recognized as precursors or risk factors for SUDs, to be targeted, engaged and modified for effective addiction prevention.Peer reviewe

    Prevalence of high blood pressure in Iranian adults based on the 2017 ACC/AHA guideline

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    Background:: In 2017, American College of Cardiology (ACC) and the American Heart Association (AHA) presented a new guideline for assessing blood pressure in adults. This study aimed to assess the prevalence of hypertension in Iranian adults based on ACC/AHA 2017 guideline. Methods: Data from 9801 Iranian adults (59.2 women) aged between 20-69 years were obtained from the sixth round of National Surveillance of Risk Factors of Non-Communicable Diseases (SuRFNCD) performed in 2011. Blood pressure was classified as normal, elevated blood pressure, and stage 1 and 2 hypertension using a weighted analysis and 2017 ACC/AHA guidelines. Data were presented as prevalence and 95 confidence interval (95 CI). All analyses were performed in Stata/SE 14.0. Results: Overall prevalence of hypertension in Iranian men was 52.0. Also, 32.9 (95 CI: 29.9-36.0) and 19.1 (95 CI: 16.921.6) of men had stage 1 and 2 hypertension, respectively. In addition, 44.3 of women had hypertension, of whom 26.3 (95 CI: 24.5 - 28.2) had stage 1 and 18.0 (95 CI: 16.1-20.1) stage 2 hypertension. Furthermore, 16.5 (95 CI: 14.4-18.9) and 9.6 (95 CI: 7.86-11.7) of men and women had elevated blood pressure, respectively. Conclusion: The findings of this study indicated that adopting the 2017 ACC/AHA guidelines showed a higher prevalence of adult hypertension (48.2) in Iran. In this study, the prevalence of hypertension in men was higher than in women, which was steadily increased by age in older adults in both sexes. © Iran University of Medical Sciences

    Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches

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    <p>Abstract</p> <p>Background</p> <p>Research suggests that food intolerance may be a precipitating factor for migraine like headaches.</p> <p>Aim</p> <p>To evaluate the effectiveness of the ELISA (Enzyme Linked Immuno-Sorbent Assay) Test and subsequent dietary elimination advice for the prevention of migraine like headaches.</p> <p>Design</p> <p>Randomised controlled trial.</p> <p>Setting</p> <p>Community based volunteers in the UK.</p> <p>Participants</p> <p>Volunteers who met the inclusion criteria for migraine like headaches and had one or more food intolerance were included in the study. Participants received either a true diet (n = 84) or a sham diet (n = 83) sheet. Participants were advised to remove the intolerant foods from their diet for 12 weeks.</p> <p>Main outcome measures</p> <p>Number of headache days over a 12 week period (item A MIDAS questionnaire). Other measures includes the total MIDAS score and total HIT-6 score.</p> <p>Results</p> <p>The results indicated a small decrease in the number of migraine like headaches over 12 weeks, although this difference was not statistically significant (IRR 1.15 95% CI 0.94 to 1.41, p = 0.18). At the 4 week assessment, use of the ELISA test with subsequent diet elimination advice significantly reduced the number of migraine like headaches (IRR 1.23 95%CI 1.01 to 1.50, p = 0.04). The disability and impact on daily life of migraines were not significantly different between the true and sham diet groups.</p> <p>Conclusions</p> <p>Use of the ELISA test with subsequent diet elimination advice did not reduce the disability or impact on daily life of migraine like headaches or the number of migraine like headaches at 12 weeks but it did significantly reduce the number of migraine like headaches at 4 weeks.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRTCN89559672">ISRTCN89559672</a></p

    Safety, Efficacy and Determinants of Response of Allogeneic CD19-Specific CAR-NK Cells in CD19+ B Cell Tumors: A Phase 1/2 Trial

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    There is a pressing need for allogeneic chimeric antigen receptor (CAR)-immune cell therapies that are safe, effective and affordable. We conducted a phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 chimeric antigen receptor and interleukin-15 (CAR19/IL-15) in 37 patients with CD19+ B cell malignancies. The primary objectives were safety and efficacy, defined as day 30 overall response (OR). Secondary objectives included day 100 response, progression-free survival, overall survival and CAR19/IL-15 NK cell persistence. No notable toxicities such as cytokine release syndrome, neurotoxicity or graft-versus-host disease were observed. The day 30 and day 100 OR rates were 48.6% for both. The 1-year overall survival and progression-free survival were 68% and 32%, respectively. Patients who achieved OR had higher levels and longer persistence of CAR-NK cells. Receiving CAR-NK cells from a cord blood unit (CBU) with nucleated red blood cells ≤ 8 × 107 and a collection-to-cryopreservation time ≤ 24 h was the most significant predictor for superior outcome. NK cells from these optimal CBUs were highly functional and enriched in effector-related genes. In contrast, NK cells from suboptimal CBUs had upregulation of inflammation, hypoxia and cellular stress programs. Finally, using multiple mouse models, we confirmed the superior antitumor activity of CAR/IL-15 NK cells from optimal CBUs in vivo. These findings uncover new features of CAR-NK cell biology and underscore the importance of donor selection for allogeneic cell therapies
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