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Summary: We tested the feasibility of a fracture prevention decision aid in an online patient portal. The decision aid was acceptable for patients and successfully decreased decisional conflict. This study suggests the possible utility of leveraging the patient portal to enhance patient education and decision making in osteoporosis care. Introduction: Although interventions have improved osteoporosis screening and/or treatment for certain populations of high-risk patients, recent national studies suggest that large-scale uptake of these interventions has been limited. We aimed to determine the feasibility and potential efficacy of a patient portal-based osteoporosis decision aid (DA). Methods: We conducted a pilot randomized controlled trial of primary care patients aged ≥55 who were enrolled in a patient portal and had a T-score of <−1. Intervention subjects were provided a link to a patient DA. The DA contained a 10-year fracture risk calculator, summary of medication risks and benefits (prescription and nonprescription), and an elicitation of values. Subjects completed questionnaires assessing the primary outcomes of decisional conflict and preparation for decision making and secondary outcomes related to feasibility and planning for a larger trial. Charts were reviewed for physician-subject interactions and medication uptake. Results: The DA was acceptable to subjects, but 17 % of the patients in the decision aid arm incorrectly entered their T-scores into FRAX-based risk calculator. Decisional conflict was lower post-intervention for those who were randomized to the decision aid arm compared to controls (17.8 vs. 47.1, p < .001), and there was a significant difference in the percentage of patients who made a treatment decision at 3 months. No significant differences were observed in medication uptake. Conclusions: A portal-based osteoporosis DA was acceptable and improved several measures of decision quality. Given its effect on improving the quality of patients' decisions, future studies should examine whether it improves physician guideline adherence or medication adherence uptake among treated patients. [ABSTRACT FROM AUTHOR]

Structural modules that specifically recognize-or read-methylated or acetylated lysine residues on histone peptides are important components of chromatin-mediated signaling and epigenetic regulation of gene expression. Deregulation of epigenetic mechanisms is associated with disease conditions, and antagonists of acetyl-lysine binding bromodomains are efficacious in animal models of cancer and inflammation, but little is known regarding the druggability of methyl-lysine binding modules. We conducted a systematic structural analysis of readers of methyl marks and derived a predictive druggability landscape of methyl-lysine binding modules. We show that these target classes are generally less druggable than bromodomains, but that some proteins stand as notable exceptions. [ABSTRACT FROM AUTHOR]

To clarify the mechanism of inhibition of immune precipitation by early components of the classical pathway of complement, aggregation of-125I-BSA-rabbit anti-BSA antibody complexes was performed in the presence of purified C1. C1-inactivator (C1-In) and C4, C1 delayed the rate of immune precipitation in a concentration dependent manner. This phenomenon was not influenced by the presence of 0.3 mM p-nitrophenyl-p-guanidinobenzoate (NPGB) which inhibits C1 activation. The antiaggregational effect of C1 was reversed by 10 mM EDTA and by C1-In at a C1-In/C1 molar ratio ≥ of 4/1 . C1-In was not effective when the reaction was performed in the presence of NPGB. Thus, although the inhibitory effect of C1 on immune precipitation was not dependent upon Cl activation, the formation of C1 was required to observe the effect of C1-In. The addition of C4 to C1 did not modify the slow aggregation of complexes, even when a limiting concentration of C1 was used, C1-In and EDTA were both able to cause similar rapid precipitation of complexes prepared in the presence of C1 and C4. demonstrating that C4 did not play a significant role in delaying the precipitation reaction. However, soluble complexes prepared in the presence of C1 and C4 were specifically precipitated by the addition of excess anti-C4 antibody, attesting to the binding of C4 to immune complexes. These observations suggest that the processing of immune complexes in vivo may not be similar in different classical pathway complement deficiency states. [ABSTRACT FROM AUTHOR]

Abstract: Wet atmospheric deposition of dissolved N, P and Si species is studied in well-mixed coastal ecosystem to evaluate its potential to stimulate photosynthetic activities in nutrient-depleted conditions. Our results show that, during spring, seawater is greatly depleted in major nutrients: Dissolved Inorganic Nitrogen (DIN), Dissolved Inorganic Phosphorus (DIP) and Silicic acid (Si), in parallel with an increase of phytoplanktonic biomass. In spring (March–May) and summer (June–September), wet atmospheric deposition is the predominant source (>60%, relative to riverine contribution) for nitrates and ammonium inputs to this N-limited coastal ecosystem. During winter (October–February), riverine inputs of DIN predominate (>80%) and are annually the most important source of DIP (>90%). This situation allows us to calculate the possibility for a significant contribution to primary production in May 2003, from atmospheric deposition (total input for DIN ≈300kgkm−2 month−1). Based on usual Redfield ratios and assuming that all of the atmospheric-derived N (AD-N) in rainwater is bioavailable for phytoplankton growth, we can estimate new production due to AD-N of 950mgCm−2 month−1, during this period of depletion in the water column. During the same episode (May 2003), photosynthetic activity rate, considered as gross primary production, was estimated to approximately 30 300mgCm−2 month−1. Calculation indicates that new photosynthetic activity due to wet atmospheric inputs of nitrogen could be up to 3%. [Copyright &y& Elsevier]

The main clinical features in four patients with IgG1k paraproteinaemia and acquired complement deficiency included xanthomatous skin lesions (in three), panniculitis (in three) and hepatitis (in two). Hypocomplementaemia concerned the early classical pathway components - in particular C1q. Metabolic studies employing 125I-C1q revealed a much faster catabolism of this protein in the four patients than in five normal controls and three patients with cryoglobulinaemia (mean fractional catabolic rates respectively: 23.35%/h; 1.44%/h; 5.84%/h)- Various experiments were designed to characterize the mechanism of the hypocomplementaemia; the patients' serum, purified paraprotein, blood cells, bone marrow cells, or xanthomatous skin lesions did not produce significant complement activation or C1q binding. When three of the patients (two with panniculitis and hepatitis) were injected with 123I-C1q, sequential gamma-camera imaging demonstrated rapid accumulation of the radionuclide in the liver, suggesting that complement activation takes place in the liver where it could produce damage. [ABSTRACT FROM AUTHOR]

Objective: To estimate the effectiveness of ovarian cancer screening with CA 125 and transvaginal sonography.Design: Decision analysis was used to examine the no-screen compared with the screen strategy.Setting: Estimates of cancer incidence, survival, and life expectancy were derived from population-based data and clinical series.Subjects: A cohort of 40-year-old women of all races and residing in the United States.Interventions: A one-time screening intervention. The criterion standard for diagnosis of ovarian cancer was evaluation with exploratory laparotomy.Main Outcome Measure: Average years of life expectancy gained by women in the screened group.Results: Screening for ovarian cancer with a combination of CA 125 and transvaginal sonography increases the average life expectancy in the population by less than 1 day.Conclusions: Given the limited effect on overall life expectancy, it is unlikely that mass screening for ovarian cancer with CA 125 and transvaginal sonography would be an effective health policy. [ABSTRACT FROM AUTHOR]