In vivo impact of a 4 bp deletion mutation in the DLX3 gene on bone development

AbstractDistal-less 3 (DLX3) gene mutations are etiologic for Tricho-Dento-Osseous syndrome. To investigate the in vivo impact of mutant DLX3 on bone development, we established transgenic (TG) mice expressing the c.571_574delGGGG DLX-3 gene mutation (MT-DLX3) driven by a mouse 2.3 Col1A1 promoter. Microcomputed tomographic analyses demonstrated markedly increased trabecular bone volume and bone mineral density in femora from TG mice. In ex vivo experiments, TG mice showed enhanced differentiation of bone marrow stromal cells to osteoblasts and increased expression levels of bone formation markers. However, TG mice did not show enhanced dynamic bone formation rates in in vivo fluorochrome double labeling experiments. Osteoclastic differentiation capacities of bone marrow monocytes were reduced in TG mice in the presence of osteoclastogenic factors and the numbers of TRAP(+) osteoclasts on distal metaphyseal trabecular bone surfaces were significantly decreased. TRACP 5b and CTX serum levels were significantly decreased in TG mice, while IFN-γ levels were significantly increased. These data demonstrate that increased levels of IFN-γ decrease osteoclast bone resorption activities, contributing to the enhanced trabecular bone volume and mineral density in these TG mice. These data suggest a novel role for this DLX-3 mutation in osteoclast differentiation and bone resorption

Quality of care received and patient-reported regret in prostate cancer: Analysis of a population-based prospective cohort

BACKGROUND: Meeting quality of care standards in oncology is recognized as important by physicians, professional organizations, and payers. Data from a population-based cohort of patients with prostate cancer were used to examine whether receipt of care was consistent with published consensus metrics and whether receiving high-quality care was associated with less patient-reported treatment decisional regret. METHODS: Patients with incident prostate cancer were enrolled in collaboration with the North Carolina Central Cancer Registry, with an oversampling of minority patients. Medical record abstraction was used to determine whether participants received high-quality care based on 5 standards: 1) discussion of all treatment options; 2) complete workup (prostate-specific antigen, Gleason grade, and clinical stage); 3) low-risk participants did not undergo a bone scan; 4) high-risk participants treated with radiotherapy (RT) received androgen deprivation therapy; and 5) participants treated with RT received conformal or intensity-modulated RT. Treatment decisional regret was assessed using a validated instrument. RESULTS: A total of 804 participants were analyzed. Overall, 66% of African American and 73% of white participants received care that met all standards (P =.03); this racial difference was confirmed by multivariable analysis. Care that included “discussion of all treatment options” was found to be associated with less patient-reported regret on univariable analysis (P =.03) and multivariable analysis (odds ratio, 0.59; 95% confidence interval, 0.37-0.95). CONCLUSIONS: The majority of participants received high-quality care, but racial disparity existed. Participants who discussed all treatment options appeared to have less treatment decisional regret. To the authors' knowledge, this is the first study to demonstrate an association between a quality of care metric and patient-reported outcome

Geomagnetic storm dependence on the solar flare class

Content. Solar flares are often used as precursors of geomagnetic storms. In particular, Howard and Tappin (2005) recently published in A&A a dependence between X-ray class of solar flares and Ap and Dst indexes of geomagnetic storms which contradicts to early published results. Aims. We compare published results on flare-storm dependences and discuss possible sources of the discrepancy. Methods. We analyze following sources of difference: (1) different intervals of observations, (2) different statistics and (3) different methods of event identification and comparison. Results. Our analysis shows that magnitude of geomagnetic storms is likely to be independent on X-ray class of solar flares.Comment: 3 pages, 1 tabl

MaxMatcher: Biological concept extraction using approximate dictionary lookup

Pricai 2006: Trends In Artificial Intelligence, Proceedings, 4099: pp. 1145-1149. http://dx.doi.org/10.1007/11801603_150Dictionary-based biological concept extraction is still the state-ofthe- art approach to large-scale biomedical literature annotation and indexing. The exact dictionary lookup is a very simple approach, but always achieves low extraction recall because a biological term often has many variants while a dictionary is impossible to collect all of them. We propose a generic extraction approach, referred to as approximate dictionary lookup, to cope with term variations and implement it as an extraction system called MaxMatcher. The basic idea of this approach is to capture the significant words instead of all words to a particular concept. The new approach dramatically improves the extraction recall while maintaining the precision. In a comparative study on GENIA corpus, the recall of the new approach reaches a 57% recall while the exact dictionary lookup only achieves a 26% recall

Statin use, high cholesterol and prostate cancer progression; results from HCaP-NC

Background: Statin use is associated with lower advanced prostate cancer risk and reduced prostate cancer-specific mortality, but prior studies were conducted mainly in white men. We examined the effect of statin use on risk of prostate cancer progression in a population-based, minority-enriched cohort. Methods: We used data from prostate cancer cases (45% African American) diagnosed between 2004 and 2007 who participated in the Health Care Access and Prostate Cancer Treatment in North Carolina cohort (HCaP-NC). We abstracted statin use at diagnosis. Men reported if they had ever been diagnosed with high cholesterol. Multivariable Cox proportional hazards analysis was used to examine associations between statin use and risk of prostate cancer progression (biochemical recurrence or secondary treatment), overall and by race. In secondary analysis, we examined the association between high cholesterol and risk of progression, overall, and by statin use. Results: Of 669 men, 244 (36%) were statin users at diagnosis. During 3.8 years median follow-up, 138 men experienced prostate cancer progression. There was no association between statin use and risk of progression, either overall (HR 1.03; 95%CI 0.72-1.46) or stratified by race. High cholesterol was inversely associated with risk of progression, particularly among statin users (HR 0.43; 95%CI 0.20-0.94; p-interaction = 0.22) and in men with higher perceived access to care (HR 0.57; 95%CI 0.36-0.90; p-interaction = 0.03). Study limitations included a relatively small sample size, short follow-up, and lack of data regarding post diagnosis statin use. Conclusions: Statin use at diagnosis was not associated with prostate cancer progression in the population-based, minority-enriched HCaP-NC. Greater healthcare engagement, including actively controlling serum cholesterol, may be linked to better prostate cancer-specific outcomes

Four Light Neutrinos in Singular Seesaw Mechanism with Abelian Flavor Symmetry

The four light neutrino scenario, which explains the atmosphere, solar and LSND neutrino experiments, is studied in the framework of the seesaw mechanism. By taking both the Dirac and Majorana mass matrix of neutrinos to be singular, the four neutrino mass spectrum consisting of two almost degenerate pairs separated by a mass gap $\sim 1$ eV is naturally generated. Moreover the right-handed neutrino Majorana mass can be at $\sim 10^{14}$ GeV scale unlike in the usual singular seesaw mechanism. Abelian flavor symmetry is used to produce the required neutrino mass pattern. A specific example of the flavor charge assignment is provided to show that maximal mixings between the $\nu_\mu-\nu_\tau$ and $\nu_e-\nu_s$ are respectively attributed to the atmosphere and solar neutrino anomalies while small mixing between two pairs to the LSND results. The implication in the other fermion masses is also discussed.Comment: Firnal version to appear in PR

A New Upper Limit for the Tau-Neutrino Magnetic Moment

Using a prompt neutrino beam in which a nu_tau component was identified for the first time, the nu_tau magnetic moment was measured based on a search for an anomalous increase in the number of neutrino-electron interactions. One such event was observed when 2.3 were expected from background processes, giving an upper 90% confidence limit of 3.9x10^-7 Bohr magnetons.Comment: 9 pages; 1 figur

Magnetic Flux of EUV Arcade and Dimming Regions as a Relevant Parameter for Early Diagnostics of Solar Eruptions - Sources of Non-Recurrent Geomagnetic Storms and Forbush Decreases

This study aims at the early diagnostics of geoeffectiveness of coronal mass ejections (CMEs) from quantitative parameters of the accompanying EUV dimming and arcade events. We study events of the 23th solar cycle, in which major non-recurrent geomagnetic storms (GMS) with Dst <-100 nT are sufficiently reliably identified with their solar sources in the central part of the disk. Using the SOHO/EIT 195 A images and MDI magnetograms, we select significant dimming and arcade areas and calculate summarized unsigned magnetic fluxes in these regions at the photospheric level. The high relevance of this eruption parameter is displayed by its pronounced correlation with the Forbush decrease (FD) magnitude, which, unlike GMSs, does not depend on the sign of the Bz component but is determined by global characteristics of ICMEs. Correlations with the same magnetic flux in the solar source region are found for the GMS intensity (at the first step, without taking into account factors determining the Bz component near the Earth), as well as for the temporal intervals between the solar eruptions and the GMS onset and peak times. The larger the magnetic flux, the stronger the FD and GMS intensities are and the shorter the ICME transit time is. The revealed correlations indicate that the main quantitative characteristics of major non-recurrent space weather disturbances are largely determined by measurable parameters of solar eruptions, in particular, by the magnetic flux in dimming areas and arcades, and can be tentatively estimated in advance with a lead time from 1 to 4 days. For GMS intensity, the revealed dependencies allow one to estimate a possible value, which can be expected if the Bz component is negative.Comment: 27 pages, 5 figures. Accepted for publication in Solar Physic

Dietary patterns based on the Mediterranean diet and DASH diet are inversely associated with high aggressive prostate cancer in PCaP

Background: Several foods and nutrients have been linked to the development of prostate cancer, but the association between healthy dietary patterns and prostate cancer aggressiveness is less studied. The aim of this study was to evaluate the relationship between the Mediterranean diet (MED) and Dietary Approaches to Stop Hypertension (DASH) diet scores and prostate cancer aggressiveness by race. Methods: Data from the population-based, case-only North Carolina–Louisiana Prostate Cancer Project (PCaP) were used to examine the association between diet quality, measured by MED and DASH scores, and prostate cancer aggressiveness in 1899 African American (AA) and European American (EA) research subjects. Dietary intake was assessed using a modified National Cancer Institute Diet History Questionnaire. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for high versus low-intermediate aggressive prostate cancer. Results: Higher MED scores were inversely associated with high aggressive prostate cancer overall (OR: 0.66; 95% CI: 0.46, 0.95 for high versus low scores); results were similar for AA and EA men. A weaker inverse association between DASH scores and prostate cancer aggressiveness was found (OR: 0.76; 95% CI: 0.55, 1.06). Conclusions: Higher diet quality, as represented by a Mediterranean-style diet or DASH diet, may reduce the odds of high aggressive prostate cancer

Mononuclear phagocyte system function and nanoparticle pharmacology in obese and normal weight ovarian and endometrial cancer patients

Purpose: Obesity may alter mononuclear phagocyte system (MPS) function and the pharmacology and efficacy of nanoparticles therapies, such as PEGylated liposomal doxorubicin (PLD). We aimed to evaluate the relationships between hormone and chemokine mediators of MPS function and the pharmacokinetic (PK) exposure of PLD in obese and normal weight patients with ovarian and endometrial cancer. Methods: Hormone and chemokine mediators in obese and normal weight ovarian and endometrial cancer patients were measured. A separate pharmacology study was performed that evaluated the relationship between serum hormone concentrations, MPS function, and PK disposition of PLD in refractory ovarian cancer patients. Results: Univariate analysis revealed a significant relationship between serum estradiol and body mass index (OR 8.64, 95% CI 2.67–28.0, p < 0.001). Estrone and testosterone concentrations were positively correlated with MPS function (ρ = 0.57 and 0.53, p = 0.14 and 0.18, respectively) and inversely correlated with PLD PK exposure (ρ = − 0.75 and − 0.76, respectively, p = 0.02 for both). Conclusions: Higher MPS function resulting in reduced PLD exposure is a potential mechanism for reduced efficacy of PLD and other nanoparticles observed in obese patients with cancer. PK simulations suggest higher doses of PLD are required in obese patients to achieve similar exposures as standard dosing in normal weight patients