Personal mastery is associated with reduced sympathetic arousal in stressed Alzheimer caregivers

OBJECTIVES: Spousal caregivers of Alzheimer's disease patients are at increased risk for cardiovascular disease, possibly via sympathetic response to stressors and subsequent catecholamine surge. Personal mastery (i.e., belief that one can manage life's obstacles) may decrease psychological and physiological response to stressors. This study examines the relationship between mastery and sympathetic arousal in elderly caregivers, as measured by norepinephrine (NE) reactivity to an acute psychological stressor. DESIGN: Cross-sectional. SETTING: Data were collected by a research nurse in each caregiver's home. PARTICIPANTS: Sixty-nine elderly spousal Alzheimer caregivers (mean age: 72.8 years) who were not taking beta-blocking medication. INTERVENTION: After assessment for mastery and objective caregiving stressors, caregivers underwent an experimental speech task designed to induce sympathetic arousal. MEASUREMENTS: Mastery was assessed using Pearlin's Personal Mastery scale and Alzheimer patient functioning was assessed using the Clinical Dementia Rating Scale, Problem Behaviors Scale, and Activities of Daily Living Scale. Plasma NE assays were conducted using pre- and postspeech blood draws. RESULTS: Multiple regression analyses revealed that mastery was significantly and negatively associated with NE reactivity (B = -9.86, t (61) = -2.03, p = 0.046) independent of factors theoretically and empirically linked to NE reactivity. CONCLUSIONS: Caregivers with higher mastery had less NE reactivity to the stressor task. Mastery may exert a protective influence that mitigates the physiological effects of acute stress, and may be an important target for psychosocial interventions in order to reduce sympathetic arousal and cardiovascular stress among dementia caregivers.

Reduced frontal activation with increasing 2nd language proficiency

The factors influencing the degree of separation or overlap in the neuronal networks responsible for the processing of first and second language are still subject to investigation. This longitudinal study investigates how increasing second language proficiency influences activation differences during lexico-semantic processing of first and second language. Native English speaking exchange students learning German were examined with functional magnetic resonance imaging while reading words in three different languages at two points in time: at the beginning of their stay (day 1) and 5 months later (day 2), when second language proficiency had significantly increased. On day 1, second language words evoked more frontal activation than words from the mother tongue. These differences were diminished on day 2. We therefore conclude that with increasing second language proficiency, lexico-semantic processing of second language words needs less frontal control. Our results demonstrate that lexico-semantic processing of first and second language converges onto similar networks as second language proficiency increases.

High-resolution ultrasound confirms reduced synovial hyperplasia following rituximab treatment in rheumatoid arthritis

OBJECTIVE: To assess the response of RA patients to rituximab (RTX) treatment using a sensitive imaging technique for synovitis. METHODS: Twenty-three RA patients were treated with two 1000-mg infusions of the B-cell depleting antibody, RTX, in an observational protocol. Clinical response was assessed by the European League Against Rheumatism (EULAR) response criteria. High-resolution grey-scale and colour-coded power Doppler (PD) ultrasonography was performed at baseline and 6 months after RTX. The second to fifth MCP and PIP joints were bilaterally examined with joints in a neutral 0 position from a palmar view and scored from 0 to 3. RESULTS: Median disease activity score (DAS28) improved from 5.03 to 3.56 (P = 0.001), which corresponded to a EULAR moderate response in 11 of 23 patients and a EULAR good response in another 6 patients. Improved control of disease activity by RTX was also indicated by tapering of median daily corticosteroid doses from 10 to 5 mg, without flare ups. Mean grey-scale scores correlated with the swollen joint count at baseline (r = 0.484, P = 0.022) and month 6 (r = 0.519, P = 0.011). Mean grey-scale scores improved upon RTX from a 0.90 median (range 0.13-1.87) to 0.75 (range 0.19-1.50, P = 0.023). Frequency of PD positive joints was low (6.1%) at baseline and did not significantly change following RTX treatment. CONCLUSIONS: High-resolution grey-scale ultrasonography (US) examination confirmed reduced synovial hyperplasia, but the applied PD method displayed no significant changes. Therefore, only grey-scale US is recommended in follow-up examinations after RTX treatment.

Detection of pulmonary emboli with CT angiography at reduced radiation exposure and contrast material volume: comparison of 80 kVp and 120 kVp protocols in a matched cohort

The detection rate of pulmonary emboli (PE) with computed tomography angiography (CTA) using either a standard or a low-dose protocol, combining reduced radiation exposure and iodine delivery rate, was retrospectively analyzed in a matched cohort of 120 patients.

Detection of urinary stones at reduced radiation exposure: a phantom study comparing computed radiography and a low-dose digital radiography linear slit scanning system

OBJECTIVE: In this experimental study we assessed the diagnostic performance of digital linear slit scanning radiography compared with computed radiography (CR) for the detection of urinary calculi in an anthropomorphic phantom imitating patients weighing approximately 58-88 kg. CONCLUSION: Compared with CR, linear slit scanning radiography is superior for the detection of urinary stones and may be used for pretreatment localization and follow-up at a lower patient exposure.

Decreased hypoxia-induced neovascularization in angiopoietin-2 heterozygous knockout mouse through reduced MMP activity

BACKGROUND/AIMS: Proliferative diabetic retinopathy is characterized by the formation of retinal neovascularization. Angiopoietin-2 (Ang-2) and matrix metalloproteinase (MMP) play a critical role in angiogenesis. However, the precise location and function of Ang-2 during formation of retinal neovascularizations driven by hypoxia in relation to MMP activity have not been elucidated. In this study, we investigated the response of Ang-2 heterozygous knockout retinas (Ang2(+/-) mouse) to hypoxia and its link to MMP activity in an oxygen-induced retinopathy (OIR) model. METHODS: Pre-retinal neovascularizations were quantitated in vertical sections. Intra-retinal angiogenesis was assessed by whole mount immunofluorescence staining of retinas. MMP activity was examined in retinal protein lysate and whole mount retinal in situ zymography. RESULTS: Ang2(+/-) retinas subjected to the OIR model showed 33% reduced neovascularization and 271% increased avascular zones at postnatal day 17. In the OIR model, Ang-2 was modestly expressed in pre-retinal neovascularizations and venules, but strongly in arterioles and capillary sprouts. MMPs were activated in close association to where Ang-2 is expressed. MMP activity was substantially decreased in Ang2(+/-) retinas. CONCLUSIONS: Our present data suggest the spatially concomitant expression of Ang2 and MMPs, and that Ang2 modulates hypoxia-induced neovascularization by regulating MMP activity.

Clinical outcomes of patients with low-flow, low-gradient, severe aortic stenosis and either preserved or reduced ejection fraction undergoing transcatheter aortic valve implantation

AIMS Our aim was to evaluate the invasive haemodynamic indices of high-risk symptomatic patients presenting with 'paradoxical' low-flow, low-gradient, severe aortic stenosis (AS) (PLF-LG) and low-flow, low-gradient severe AS (LEF-LG) and to compare clinical outcomes following transcatheter aortic valve implantation (TAVI) among these challenging AS subgroups. METHODS AND RESULTS Of 534 symptomatic patients undergoing TAVI, 385 had a full pre-procedural right and left heart catheterization. A total of 208 patients had high-gradient severe AS [HGAS; mean gradient (MG) ≥40 mmHg], 85 had PLF-LG [MG ≤ 40 mmHg, indexed aortic valve area [iAVA] ≤0.6 cm(2) m(-2), stroke volume index ≤35 mL/m(2), ejection fraction (EF) ≥50%], and 61 had LEF-LG (MG ≤ 40 mmHg, iAVA ≤0.6 cm(2) m(-2), EF ≤40%). Compared with HGAS, PLF-LG and LEF-LG had higher systemic vascular resistances (HGAS: 1912 ± 654 vs. PLF-LG 2006 ± 586 vs. LEF-LG 2216 ± 765 dyne s m(-5), P = 0.007) but lower valvulo-arterial impedances (HGAS: 7.8 ± 2.7 vs. PLF-LG 6.9 ± 1.9 vs. LEF-LG 7.7 ± 2.5 mmHg mL(-1) m(-2), P = 0.027). At 30 days, no differences in cardiac death (6.5 vs. 4.9 vs. 6.6%, P = 0.90) or death (8.4 vs. 6.1 vs. 6.6%, P = 0.88) were observed among HGAS, PLF-LG, and LEF-LG groups, respectively. At 1 year, New York Heart Association functional improvement occurred in most surviving patients (HGAS: 69.2% vs. PLF-LG 71.7% vs. LEF-LG 89.3%, P = 0.09) and no significant differences in overall mortality were observed (17.6 vs. 20.5 vs. 24.5%, P = 0.67). Compared with HGAS, LEF-LG had a higher 1 year cardiac mortality (adjusted hazard ratio 2.45, 95% confidence interval 1.04-5.75, P = 0.04). CONCLUSION TAVI in PLF-LG or LEF-LG patients is associated with overall mortality rates comparable with HGAS patients and all groups profit symptomatically to a similar extent.

Reduced estimated GFR and cancer mortality.

BACKGROUND Chronic kidney disease is associated with an increased risk of cancer, but whether reduced kidney function also leads to increased cancer mortality is uncertain. The aim of our study was to assess the independent effects of reduced kidney function on the risk of cancer deaths. STUDY DESIGN Prospective population-based cohort study. SETTING & PARTICIPANTS Participants of the Blue Mountains Eye Study (n=4,077; aged 49-97 years). PREDICTOR Estimated glomerular filtration rate (eGFR). OUTCOMES Overall and site-specific cancer mortality. RESULTS During a median follow-up of 12.8 (IQR, 8.6-15.8) years, 370 cancer deaths were observed in our study cohort. For every 10-mL/min/1.73 m(2) reduction in eGFR, there was an increase in cancer-specific mortality of 18% in the fully adjusted model (P<0.001). Compared with participants with eGFR ≥ 60 mL/min/1.73 m(2), the adjusted HR for cancer-specific mortality for those with eGFR<60 mL/min/1.73 m(2) was 1.27 (95% CI, 1.00-1.60; P=0.05). This excess cancer mortality varied with site, with the greatest risk for breast and urinary tract cancer deaths (adjusted HRs of 1.99 [95% CI, 1.05-3.85; P=0.01] and 2.54 [95% CI, 1.02-6.44; P=0.04], respectively). LIMITATIONS Residual confounding, such as from unmeasured socioeconomic factors and the potential effects of erythropoiesis-stimulating agents on cancer deaths, may have occurred. CONCLUSIONS eGFR<60 mL/min/1.73m(2) appears to be a significant risk factor for death from cancer. These effects appear to be site specific, with breast and urinary tract cancers incurring the greatest risk of death among those with reduced kidney function.

1.59 Reduced inflammatory potential of circulating gammadelta T cells in pregnancy induced improvement of Rheumatoid Arthritis

BACKGROUND AND OBJECTIVES During pregnancy, gammadelta T cells expand at the fetomaternal interface where they induce a tolerogenic milieu. Patients with rheumatoid arthritis (RA) experience a spontaneous improvement of their disease during pregnancy and a postpartum aggravation. By contrast, pregnant patients with ankylosing spondylitis (AS) often experience persistent active disease. We hypothesised that the pregnancy related modulation of disease activity in RA patients versus AS patients is associated with numerical and functional changes of circulating gammadelta T cells. MATERIAL AND METHODS The frequency of surface markers and the intracellular cytokine profile of freshly isolated gammadelta T cells from RA (n = 54) and AS (n = 26) patients and healthy controls (n = 40) were analysed at each trimester during pregnancy and 6-8 weeks postpartum by flow cytometry. RESULTS Very discrete changes of Vdelta1 or Vdelta2 frequency were seen during pregnancy and postpartum in healthy controls and AS patients. In RA, however, the frequency of Vdelta2 cells decreased in the third trimester when disease activity was low. Low percentages of Vdelta 2 cells were also found in non-pregnant RA patients with active arthritis, yet only pregnant RA patients showed reduced percentages of Vdelta2 cells positive for the activation marker CD69 and the intracellular cytokine TNFalpha. Similarly, Vdelta1 + TNFalpha + cells were lower in pregnant RA patients compared to non-pregnant RA patients. The percentage of Vdelta2 + TNFalpha + cells, Vdelta2+ CD69+ and Vdelta1+ CD69+ cells correlated with disease activity in RA. As for the receptors which modulate cytotoxicity, RA patients showed a rise of the anti-cytotoxic receptor NKG2A on Vdelta1 cells in the 2(nd) trimester and a decrease postpartum. Since the pro-cytotoxic receptor NKG2D remained unchanged, the NKG2D/NKG2A ratio on Vdelta1 cells was reduced in RA patients during pregnancy. In AS patients, persistent disease activity during pregnancy was reflected by an increased frequency of Vdelta2+ CD69+ cells and an unchanged frequency of Vdelta2+ TNFalpha+ cells. In addition, pregnant AS patients showed an increased frequency of Vdelta1+CD161+ cells. CONCLUSIONS Disease amelioration of RA during pregnancy correlates with changes of cell activation, pro-inflammatory cytokines and anti-cytotoxic receptors of gammadelta T cells. By contrast, active disease during pregnancy as found in AS is associated with unchanged inflammatory responses of gammadelta T cells. Since gammadelta T cells remain unchanged in healthy pregnant controls, the modulation of gammadelta T cells in RA rather seems to be an effect of improved disease than of pregnancy itself.