Search

Earlier studies showed that the DNA-binding protein, Bright/ARID3a bound to a subset of human and mouse immunoglobulin heavy chain promoters where it enhanced expression. Indeed, mice with transgenic expression of ARID3a in all B lymphocytes have expanded MZ B cells and produce anti-nuclear antibodies (ANAs). Consistent with our findings in mice, we observed that human systemic lupus erythematosus (SLE) patients had expanded numbers of peripheral blood ARID3a+ B cells that were associated with increased disease activity (p = 0.0038). We hypothesized that ARID3a+ naïve B cells would eventually produce autoantibodies, explaining associations between ARID3a expression and disease activity in lupus. Unlike healthy controls, ARID3a was expressed in the naïve B cell population in SLE patients, and we hypothesized that these might represent expansions of autoreactive cells. Therefore, monoclonal antibodies were generated from single-sorted naïve B cells derived from patients with normal (ARID3aN) and high (ARID3aH) numbers of ARID3a+ B cells. We found that ARID3a expression did not correlate with autoantibody expression. Furthermore, measures of antigen specificities of autoreactive antibodies did not reveal skewing toward particular proteins. These data suggest that the association of increased disease activity in SLE with numbers of ARID3a+ B lymphocytes may be mediated by an antibody-independent mechanism. [ABSTRACT FROM AUTHOR]

Background This study aims to compare dosimetrically and radiobiologically 3 D conformal, intensity modulated radiation therapy ( IMRT), RapidArc ( RA) volumetric modulated arc therapy and proton therapy techniques for early-stage glottic cancer. Methods Ten patients were retrospectively selected. Photon treatment planning was performed using Eclipse External Beam Planning, and proton planning was performed using CMS Xio. The minimum, mean and maximum dose values for planning target volume ( PTV), mean and maximum dose values for organ at risk, % of volume of PTV receiving at least 95% of the prescription dose, and D20, D50 and D90 of carotid arteries were compared. Biological response models of tumour control probabilities and normal tissue complication probabilities were calculated. Results IMRT, RA and proton plans versus three-dimensional conformal radiotherapy (3 D-CRT) plans consistently provided superior PTV coverage and decreased mean dose to the thyroid and carotid arteries. Conclusion All these three modalities showed superiority with less variation among themselves compared with 3 D-CRT plans. Clinical investigation is warranted to determine if these treatment approaches will translate into a reduction in radiation therapy-induced toxicities. [ABSTRACT FROM AUTHOR]

Cigarette smoke (CS) exposure increases the frequency and severity of respiratory tract infections. Despite this association, the mechanisms underlying the increased susceptibility to respiratory virus infection are poorly understood. Retinoic acid-inducible gene I (RIG-I) is an important regulator of influenza virus-induced expression of antiviral cytokines, mainly interferons (IFNs), which are necessary to clear viral infections. In this study, we compared the innate cytokine responses of two mouse CS exposure models following a challenge with influenza A virus (IAV): 1) exposure of the mice to cigarette smoke extract (CSE) intratracheally and 2) exposure of the mice to CS in a whole body exposure chamber. Both intratracheal CSE treatment and whole body CS exposure caused antiviral immunosuppression in these mice, and both CS exposure methods inhibited RIG-I induction. CS attenuated influenza-induced antiviral IFNs and IP-10 expression in vivo. However, we did not find that CS inhibited induction of the proinflammatory cytokines IL-6 and TNF-α, whose expression was induced by IAV. Interestingly, IAV infection also increased Toll-like receptor 3 (TLR3) expression in mouse lung, but CS exposure did not impact TLR3 induction in these mice. Together, the results support our previous finding in a human lung organ culture model that the suppression of RIG-I induction and antiviral cytokine responses by CS are likely important in the enhanced susceptibility of smokers to influenza infection in the lung. [ABSTRACT FROM AUTHOR]

Proton T2 relaxation times of metabolites in the human brain were measured using point resolved spectroscopy at 3T in vivo. Four echo times (54, 112, 246 and 374 ms) were selected from numerical and phantom analyses for effective detection of the glutamate multiplet at ~ 2.35 ppm. In vivo data were obtained from medial and left occipital cortices of five healthy volunteers. The cortices contained predominantly gray and white matter, respectively. Spectra were analyzed with LCModel software using volume-localized calculated spectra of brain metabolites. The estimate of the signal strength vs. TE was fitted to a monoexponential function for estimation of apparent T2 (T2†). T2† was estimated to be similar between the brain regions for creatine, choline, glutamate and myo-inositol, but significantly different for N-acetylaspartate singlet and multiplet. T2†s of glutamate and myo-inositol were measured as 181 ± 16 and 197 ± 14 ms (mean ± SD, N = 5) for medial occipital cortices, and 180 ± 12 and 196 ± 17 ms for left occipital cortices, respectively. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In this paper we study sample size calculation methods for the asymptotic Wilcoxon-Mann-Whitney test for data with or without ties. The existing methods are applicable either to data with ties or to data without ties but not to both cases. While the existing methods developed for data without ties perform well, the methods developed for data with ties have limitations in that they are either applicable to proportional odds alternatives or have computational difficulties. We propose a new method which has a closed-form formula and therefore is very easy to calculate. In addition, the new method can be applied to both data with or without ties. Simulations have demonstrated that the new sample size formula performs very well as the corresponding actual powers are close to the nominal powers. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

BACKGROUND: Blood pressure (BP) screening in adults has been identified by the US Preventive Services Task Force as a Grade A recommendation.OBJECTIVE: To compare BP screening rates in adult patients among payer sources and provider types in two national probability samples of outpatient office visits.DESIGN/METHODS: An analysis of visit data for all patients 18 years and older in the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey-Outpatient Department (OPD) during the years 2005-2009 was performed. Data on 279,510 patient visits were analyzed, including adults seen in ambulatory or office-based settings (NAMCS, N=147,675) and hospital outpatient departments (OPD, N=131,835). BP screening rates were compared based on provider type (Family Practice, Internal Medicine, Obstetrics-Gynecology, and Cardiovascular Specialist) and payer source (Private Insurance, Medicare, Medicaid, and Self Pay).Results: Overall, BP screening rates were higher in the OPD sample (65.70% vs, 55.83%, p < .001), despite a higher mean age and higher proportion of privately insured or Medicare patients in the NAMCS sample. The odds ratio for BP screening was 1.538 for insured patients compared to self-pay in the NAMCS sample (95% CI: 1.473-1.606); however, the disparity was not observed in the OPD data. Cardiovascular specialists demonstrated the most adherence to BP screening, regardless of payer source. Overall BP screening rates are shown in Table 1.Conclusions: Analysis of two national probability samples reflected marked disparity in BP screening in adult patients based on payer source and provider type. [ABSTRACT FROM AUTHOR]

BACKGROUND: It has been suggested by national data and popular media that prevalence of obesity and elevated Blood Pressure (BP) has increased in the United States over time.OBJECTIVE: To assess the trends in the prevalence of elevated BP and obesity in adult patients, and to quantify any correlation between them using national probability data sets.DESIGN/METHODS: An analysis of visit data for all patients 18 years and older included in the 2005-09 National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey-Outpatient Department (OPD) was performed. BP data from 160,380 patient visits were analyzed, including adults seen in ambulatory or office-based settings (NAMCS, N=74,645) and hospital outpatient departments (OPD, N=85,735). Correlation between BP and BMI were calculated using the Pearson Correlation method.Results: Overall, the prevalence of hypertension decreased over time, while the prevalence of obesity increased. This data is represented in Table 1.Conclusions: This analysis suggests that while the prevalence of obesity may be increasing, the prevalence of elevated BP has actually decreased over time. This seemingly counter-intuitive finding may reflect improved BP control rates, despite obesity, which is suggested in contemporary NHANES data. [ABSTRACT FROM AUTHOR]

Background: Currently, endovascular treatment of intracranial aneurysms (ICAs) is limited by low complete occlusion rates. The advent of novel endovascular technology has expanded the applicability of endovascular therapy; however, the superiority of novel embolic devices over the traditional Guglielmi detachable coils (GDCs) is still debated. We performed a systematic review of literature that reported Raymond-Roy occlusion classification (RROC) rates of modern endovascular devices to determine their immediate and follow-up occlusion effectiveness for the treatment of unruptured saccular ICAs., Methods: A search was conducted using electronic databases (PUBMED, Cochrane, ClinicalTrials.gov, Web of Science). We retrieved studies published between 2000-2022 reporting immediate and follow-up RROC rates of subjects treated with different endovascular ICA therapies. We extracted demographic information of the treated patients and their reported angiographic RROC rates., Results: A total of 80 studies from 15 countries were included for data extraction. RROC rates determined from angiogram were obtained for 21,331 patients (72.5% females, pooled mean age: 58.2 (95% CI: 56.8-59.6), harboring 22,791 aneurysms. The most frequent aneurysm locations were the internal carotid artery (46.4%, 95% CI: 41.9%-50.9%), the anterior communicating artery (26.4%, 95% CI: 22.5%-30.8%), the middle cerebral artery (24.5%, 95% CI:19.2%-30.8%) and the basilar tip (14.4%, 95% CI:11.3%-18.3%). The complete occlusion probability (RROC-I) was analyzed for GDCs, the Woven EndoBridge (WEB), and flow diverters. The RROC-I rate was the highest in balloon-assisted coiling (73.9%, 95% CI: 65.0%-81.2%) and the lowest in the WEB (27.8%, 95% CI:13.2%-49.2%). The follow-up RROC-I probability was homogenous in all analyzed devices., Conclusions: We observed that the coil-based endovascular therapy provides acceptable rates of complete occlusion, and these rates are improved in balloon-assisted coils. Out of the analyzed devices, the WEB exhibited the shortest time to achieve >90% probability of follow-up complete occlusion (~18 months). Overall, the GDCs remain the gold standard for endovascular treatment of unruptured saccular aneurysms.

Objective: Inflammatory and immunologic cytokines and vagal activity have important roles in health and mental health, and may influence each other. The authors assessed relationships of representative biomarkers linked to disaster exposure-heart rate variability (HRV) with Interleukin-2 (IL-2, cell-medicated immunity) and Interleukin-6 (IL-6, pro-inflammatory and pro-immunologic), stratified by psychiatric diagnosis., Design: Participants were assessed for psychiatric diagnosis, IL-2, IL-6, HRV, and HR reactivity to trauma reminders., Setting: Outpatient university psychiatry clinics in Oklahoma City and Tulsa., Participants: Relocated Katrina survivors and demographically matched controls, not on psychiatric, cardiovascular, or inflammatory medications., Main Outcome Measures: SCID-IV, baseline serum IL-2 and IL-6, HRV through power spectral analysis., Results: Survivors had higher sympathetic and lower parasympathetic activity at baseline and lower parasympathetic HR reactivity than controls, with flattened parasympathetic reactivity in the presence of depression and of post-traumatic stress disorder (PTSD). Survivors' IL-2 and IL-6 did not differ from controls and did not differ in PTSD or depression. Depressed survivors' sympathetic reactivity correlated negatively with IL-2 and parasympathetic reactivity correlated positively with IL-2., Conclusions: HRV differed after hurricane exposure and with survivors& depression and/or PTSD, more sensitively capturing somatic sequelae than assessed cytokines. Higher sympathetic HR reactivity associated with lower immuno-logic IL-2 may indicate a double biological "hit" in depressed disaster survivors, possibly rendering them more vulnerable to cardiovascular and immunologic illness as well as depression. Associations of HRV with IL-2 may support reciprocal influences of cytokines and vagal activity. Lack of significant correlations of IL-6 with HRV measures is consistent with its pleiotropic role.

Proton T(2) relaxation times of metabolites in the human brain were measured using point resolved spectroscopy at 3T in vivo. Four echo times (54, 112, 246 and 374 ms) were selected from numerical and phantom analyses for effective detection of the glutamate multiplet at ~ 2.35 ppm. In vivo data were obtained from medial and left occipital cortices of five healthy volunteers. The cortices contained predominantly gray and white matter, respectively. Spectra were analyzed with LCModel software using volume-localized calculated spectra of brain metabolites. The estimate of the signal strength vs. TE was fitted to a monoexponential function for estimation of apparent T(2) (T(2)(†)). T(2)(†) was estimated to be similar between the brain regions for creatine, choline, glutamate and myo-inositol, but significantly different for N-acetylaspartate singlet and multiplet. T(2)(†)s of glutamate and myo-inositol were measured as 181 ± 16 and 197 ± 14 ms (mean ± SD, N = 5) for medial occipital cortices, and 180 ± 12 and 196 ± 17 ms for left occipital cortices, respectively., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objective: To evaluate short- and long-term safety and efficacy of duloxetine in women with predominant stress urinary incontinence (SUI)., Research Design and Methods: The study was a 6-week, double-blind, randomised, parallel, placebo-controlled study followed by an uncontrolled open-label extension (OLE) run in 342 study centres in 16 European countries. Women with predominant SUI were randomly assigned to placebo (n = 1380) or duloxetine 40 mg twice daily (n = 1378) for 6 weeks. Completers of the acute phase were enrolled in the OLE, which had a minimum duration of 6 weeks and ended, based on the approval status of duloxetine in the participating country., Main Outcome Measures: The primary outcome measure was the change in incontinence episode frequency (IEF) over 6 weeks. Secondary outcome measures were the long-term maintenance of effect on IEF and Patient Global Impression of Improvement (PGI-I), the short- and long-term impact on quality of life using the King's Health Questionnaire (KHQ), and the long-term safety of duloxetine., Results: After 6 weeks, the decrease in weekly IEF was significantly greater with duloxetine treatment compared to placebo (-50.0 vs. -29.9%; p < 0.001). The percentage of responders (defined as > or =50% decrease in IEF) was significantly higher with duloxetine treatment than with placebo (50.6 vs. 31.2%; p < 0.001). Duloxetine treatment was associated with improvements in weekly pad use (-31.4%), PGI-I ratings (63.6%), and KHQ score (-6.25) compared to placebo (-12.5%, 48.5% and -3.13, respectively, all p < 0.001). Treatment-emergent adverse events were significantly more common during duloxetine treatment (48.3%) than placebo (33.3%), (p < 0.001). Of the 2290 patients continuing into the OLE, 1165 (42.2%) completed the available duration, and 592 (21.5%) discontinued because of an adverse event (percentages relative to total randomised patients). Long-term efficacy in the OLE was assessed over a 72-week period and was maintained over that time. However, the results should be interpreted within the context that better responding patients are more likely to remain on duloxetine, while patients responding poorly are more likely to discontinue over time., Conclusions: Duloxetine seems to be an efficacious treatment with an acceptable safety profile for women with SUI. Achieved improvement is maintained over the longer term in those women who remain on therapy.