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1.
S. Schalla C. Jaarsma S.C. Bekkers J. Waltenberger R. Dennert H.J. Crijns J. Wildberger S. Heymans H-P. Brunner-La Rocca 《Netherlands heart journal》2015,23(4):232-240
Background
Dilated cardiomyopathy and ischaemic heart disease can both lead to right ventricular (RV) dysfunction. Direct comparisons of the two entities regarding RV size and function using state-of-the-art imaging techniques have not yet been performed. We aimed to determine RV function and volume in dilated cardiomyopathy and ischaemic heart disease in relation to left ventricular (LV) systolic and diastolic function and systolic pulmonary artery pressure.Methods and results
A well-characterised group (cardiac magnetic resonance imaging, echocardiography, coronary angiography and endomyocardial biopsy) of 46 patients with dilated cardiomyopathy was compared with LV ejection fraction (EF)-matched patients (n = 23) with ischaemic heart disease. Volumes and EF were determined with magnetic resonance imaging, diastolic LV function and pulmonary artery pressure with echocardiography.After multivariable linear regression, four factors independently influenced RVEF (R2 = 0.51, p < 0.001): LVEF (r = 0.54, p < 0.001), ratio of peak early and peak atrial transmitral Doppler flow velocity as measure of LV filling pressure (r = − 0.52, p < 0.001) and tricuspid regurgitation flow velocity as measure of pulmonary artery pressure (r = − 0.38, p = 0.001). RVEF was significantly worse in patients with dilated cardiomyopathy compared with ischaemic heart disease: median 48 % (interquartile range (IQR) 37–55 %) versus 56 % (IQR 48–63 %), p < 0.05.Conclusions
In patients with dilated cardiomyopathy and ischaemic heart disease, RV function is determined by LV systolic and diastolic function, the underlying cause of LV dysfunction, and pulmonary artery pressure. It was demonstrated that RV function is more impaired in dilated cardiomyopathy. 相似文献2.
Background
Recent developments in sequencing technology have facilitated widespread investigations of genomic variants, including continuous stretches of homozygous genomic regions. For cattle, a large proportion of these runs of homozygosity (ROH) are likely the result of inbreeding due to the accumulation of elite alleles from long-term selective breeding programs. In the present study, ROH were characterized in four cattle breeds with whole genome sequence data and the distribution of predicted functional variants was detected in ROH regions and across different ROH length classes.Results
On average, 19.5 % of the genome was located in ROH across four cattle breeds. There were an average of 715.5 ROH per genome with an average size of ~750 kbp, ranging from 10 (minimum size considered) to 49,290 kbp. There was a significant correlation between shared short ROH regions and regions putatively under selection (p < 0.001). By investigating the relationship between ROH and the predicted deleterious and non-deleterious variants, we gained insight into the distribution of functional variation in inbred (ROH) regions. Predicted deleterious variants were more enriched in ROH regions than predicted non-deleterious variants, which is consistent with observations in the human genome. We also found that increased enrichment of deleterious variants was significantly higher in short (<100 kbp) and medium (0.1 to 3 Mbp) ROH regions compared with long (>3 Mbp) ROH regions (P < 0.001), which is different than what has been observed in the human genome.Conclusions
This study illustrates the distribution of ROH and functional variants within ROH in cattle populations. These patterns are different from those in the human genome but consistent with the natural history of cattle populations, which is confirmed by the significant correlation between shared short ROH regions and regions putatively under selection. These findings contribute to understanding the effects of inbreeding and probably selection in shaping the distribution of functional variants in the cattle genome.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1715-x) contains supplementary material, which is available to authorized users. 相似文献3.
Background
Nitric oxide (NO) has been shown to be important in sperm function, and the concentration of NO appears to determine these effects. Studies have demonstrated both positive and negative effects of NO on sperm function, but have not been able to provide a clear link between NO concentration and the extent of exposure to NO. To study the relationship between nitric oxide and sperm capacitation in vitro, and to provide a theoretical basis for the use of NO-related preparations in improving sperm motility for in vitro fertilization, we investigated the effects of NO concentration and time duration at these concentrations on in vitro sperm capacitation in both normal and abnormal sperm groups. We manipulated NO concentrations and the time duration of these concentrations using sodium nitroprusside (an NO donor) and NG-monomethyl-L-argenine (an NO synthase inhibitor).Results
Compared to the normal sperm group, the abnormal sperm group had a longer basal time to reach the appropriate concentration of NO (p < 0.001), and the duration of time at this concentration was longer for the abnormal sperm group (p < 0.001). Both the basal time and the duration of time were significantly correlated with sperm viability and percentage of progressive sperm (p < 0.001). The experimental group had a significantly higher percentage of progressive sperm than the control group (p < 0.001).Conclusions
We hypothesize that there is a certain regularity to both NO concentration and its duration of time in regards to sperm capacitation, and that an adequate duration of time at the appropriate NO concentration is beneficial to sperm motility. 相似文献4.
P. Gal E. Parlak F. Demirel A. Adiyaman J. ten Berg A.W.J. van ’t Hof A. Elvan 《Netherlands heart journal》2015,23(9):430-435
Atrial fibrillation (AF) is associated with short-term mortality after ST-elevation myocardial infarction (STEMI), but there is limited data on the temporal association between AF and mortality after STEMI. A total of 830 patients were included (age: 62 ± 12 years, 76 % male). Patients with new-onset AF < 30 days after STEMI were divided among three subgroups: AF on the day of admission, AF 24–72 h and AF > 72 h after admission. Thirty-day mortality was assessed by telephone and via the municipal population registry. Twenty patients died < 30 days after admission. In 41 patients, AF was detected on the day of admission, in 14 patients 24–72 h after admission and in 18 patients > 72 h after admission. Mortality was higher in patients with AF on the day of admission (7.3 vs 2.2 %, p = 0.036) and 24–72 h after admission (14.3 vs 1.4 %, p < 0.001), but not in patients with AF > 72 h after admission (0 vs 1.1 %, p > 0.999). Age (odds ratio (OR) 1.123, p < 0.001), Killip class (adjusted OR 8.341, p < 0.001), AF on the day of admission (OR 3.585, p = 0.049) and 24–72 h after admission (OR 11.515, p = 0.003) were, amongst other variables, associated with an increased 30-day mortality. In conclusion, only new-onset incident AF during the first 72 h after admission was associated with 30-day mortality in STEMI patients.
Electronic supplementary material
The online version of this article (doi:10.1007/s12471-015-0709-2) contains supplementary material, which is available to authorized users. 相似文献5.
Ayedh D. Alahmari Alex J. Mackay Anant R.C. Patel Beverly S. Kowlessar Richa Singh Simon E. Brill James P. Allinson Jadwiga A. Wedzicha Gavin C. Donaldson 《Respiratory research》2015,16(1)
Rationale
Information concerning how climate and atmospheric pollutants affects physical activity in COPD patients is lacking and might be valuable in determining when physical activity should be encouraged.Methods
Seventy-three stable COPD patients recorded on daily diary cards worsening of respiratory symptoms, peak expiratory flow rate, hours spent outside the home and the number of steps taken per day. Pedometry data was recorded on 16,478 days, an average of 267 days per patient (range 29-658). Daily data for atmospheric PM10 and ozone (O3) were obtained for Bloomsbury Square, Central London from the Air Quality Information Archive databases. Daily weather data were obtained for London Heathrow from the British Atmospheric Data Archive.Results
Colder weather below 22.5 °C, reduced daily step count by 43.3 steps day per°C (95 % CI 2.14 to 84.4; p = 0.039) and activity was lower on rainy than dry days (p = 0.002) and on overcast compared to sunny days (p < 0.001). Daily step count was 434 steps per day lower on Sunday than Saturday (p < 0.001) and 353 steps per day lower on Saturday than Friday (p < 0.001). After allowance for these effects, higher O3 levels decreased activity during the whole week (-8 steps/ug/m3; p = 0.005) and at weekends (-7.8 steps/ug/m3; p = 0.032). Whilst, during the week PM10 reduced activity (p = 0.018) but not during the weekend.Conclusions
Inactivity of COPD patients is greatest on cold, wet and overcast days and at the weekends. This study also provides evidence of an independent effect of atmospheric pollution at high levels.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0229-z) contains supplementary material, which is available to authorized users. 相似文献6.
Wioleta Marut Vincent Jamier Niloufar Kavian Amélie Servettaz Paul G Winyard Paul Eggleton Awais Anwar Carole Nicco Claus Jacob Christiane Chéreau Bernard Weill Frédéric Batteux 《Arthritis research & therapy》2013,15(5):R167
Introduction
The aim of this study was to test the naturally occurring organosulfur compound dipropyltetrasulfide (DPTTS), found in plants, which has antibiotic and anticancer properties, as a treatment for HOCl-induced systemic sclerosis in the mouse.Methods
The prooxidative, antiproliferative, and cytotoxic effects of DPTTS were evaluated ex vivo on fibroblasts from normal and HOCl mice. In vivo, the antifibrotic and immunomodulating properties of DPTTS were evaluated in the skin and lungs of HOCl mice.Results
H2O2 production was higher in fibroblasts derived from HOCl mice than in normal fibroblasts (P < 0.05). DPTTS did not increase H2O2 production in normal fibroblasts, but DPTTS dose-dependently increased H2O2 production in HOCl fibroblasts (P < 0.001 with 40 μM DPTTS). Because H2O2 reached a lethal threshold in cells from HOCl mice, the antiproliferative, cytotoxic, and proapoptotic effects of DPTTS were significantly higher in HOCl fibroblasts than for normal fibroblasts. In vivo, DPTTS decreased dermal thickness (P < 0.001), collagen content in skin (P < 0.01) and lungs (P < 0.05), αSMA (P < 0.01) and pSMAD2/3 (P < 0.01) expression in skin, formation of advanced oxidation protein products and anti-DNA topoisomerase-1 antibodies in serum (P < 0.05) versus untreated HOCl mice. Moreover, in HOCl mice, DPTTS reduced splenic B-cell counts (P < 0.01), the proliferative rates of B-splenocytes stimulated by lipopolysaccharide (P < 0.05), and T-splenocytes stimulated by anti-CD3/CD28 mAb (P < 0.001). Ex vivo, it also reduced the production of IL-4 and IL-13 by activated T cells (P < 0.05 in both cases).Conclusions
The natural organosulfur compound DPTTS prevents skin and lung fibrosis in the mouse through the selective killing of diseased fibroblasts and its immunomodulating properties. DPTTS may be a potential treatment for systemic sclerosis. 相似文献7.
Zacharenia Saridaki Maria Tzardi Maria Sfakianaki Chara Papadaki Alexandra Voutsina Aristea Kalykaki Ippokratis Messaritakis Kyriakos Mpananis Dimitris Mavroudis Efstathios Stathopoulos Vassilis Georgoulias John Souglakos 《PloS one》2013,8(12)
Background
To prospectively evaluate the usefulness of the BRAFV600E mutation detection in daily clinical practice in patients with metastatic Colorectal Cancer (mCRC).Patients and Methods
504 mCRC patients treated with systemic chemotherapy ± biologics were analyzed.Results
A statistically significant higher incidence of the BRAF mutation was observed in patients with ECOG-PS 2 (p=0.001), multiple metastatic sites (p=0.002),> 65 years old (p=0.004), primary tumors located in the colon (p<0.001), high-grade tumors (p=0.001) and in those with mucinous features (p=0.037). Patients with BRAFV600E mutated tumors had a statistically significantly reduced progression-free survival (PFS) compared to wild-type (wt) ones (4.1 and 11.6 months, respectively; p<0.001) and overall survival (OS) (14.0 vs. 34.6 months, respectively; p<0.001). In the multivariate analysis the BRAFV600E mutation emerged as an independent factor associated with reduced PFS (HR: 4.1, 95% CI 2.7–6.2; p<0.001) and OS (HR: 5.9, 95% CI 3.7–9.5; p<0.001). Among the 273 patients treated with salvage cetuximab or panitumumab, the BRAFV600E mutation was correlated with reduced PFS (2.2 vs. 6.0 months; p<0.0001) and OS (4.3 vs. 17.4 months; p<0.0001).Conclusions
The presence of BRAFV600E-mutation in mCRC characterizes a subgroup of patients with distinct biologic, clinical and pathological features and is associated with very poor patients’ prognosis. 相似文献8.
C. Doesch C. Zompolou F. Streitner D. Haghi R. Schimpf B. Rudic J. Kuschyk S. O. Schoenberg M. Borggrefe T. Papavassiliu 《Netherlands heart journal》2014,22(12):557-564
Aim
To compare cardiovascular magnetic resonance (CMR)-derived right ventricular fractional shortening (RVFS), tricuspid annular plane systolic excursion with a reference point within the right ventricular apex (TAPSEin) and with one outside the ventricle (TAPSEout) with the standard volumetric approach in patients with hypertrophic cardiomyopathy (HCM).Methods and results
105 patients with HCM and 20 healthy subjects underwent CMR. In patients with HCM, TAPSEin (r = 0.31, p = 0.001) and RVFS (r = 0.35, p = 0.0002) revealed a significant but weak correlation with right ventricular ejection fraction (RVEF), whereas TAPSEout (r = 0.57, p < 0.0001) showed a moderate correlation with RVEF. The ability to predict RVEF < 45 % in HCM patients was best for TAPSEout. In patients with hypertrophic obstructive cardiomyopathy (HOCM), RVEF showed a significant but weak correlation with TAPSEout (r = 0.36, p = 0.02) and no correlation with TAPSEin (r = 0.05, p = 0.07) and RVFS (r = 0.02, p = 0.2). In patients with hypertrophic non-obstructive cardiomyopathy (HNCM), there was a moderate correlation between RVEF and TAPSEout (r = 0.57, p < 0.0001) and a weak correlation with TAPSEin (r = 0.39, p = 0.001) and RVFS (r = 0.38, p = 0.002). In the 20 healthy controls, there was a strong correlation between RVEF and all semi-quantitative measurements.Conclusion
CMR-derived TAPSEin is not suitable to determine right ventricular function in HCM patients. TAPSEout showed a good correlation with RVEF in HNCM patients but only a weak correlation in HOCM patients. TAPSEout might be used for screening but the detection of subtle changes in RV function requires the 3D volumetric approach. 相似文献9.
Eva Klingberg Mattias Lorentzon Jan G?thlin Dan Mellstr?m Mats Geijer Claes Ohlsson Elizabeth J Atkinson Sundeep Khosla Hans Carlsten Helena Forsblad-d’Elia 《Arthritis research & therapy》2013,15(6):R179
Introduction
Osteoporosis of the axial skeleton is a known complication of ankylosing spondylitis (AS), but bone loss affecting the peripheral skeleton is less studied. This study on volumetric bone mineral density (vBMD) and bone microarchitecture in AS was conducted to compare peripheral vBMD in AS patients with that in healthy controls, to study vBMD in axial compared with peripheral bone, and to explore the relation between vertebral fractures, spinal osteoproliferation, and peripheral bone microarchitecture and density.Methods
High-resolution peripheral quantitative computed tomography (HRpQCT) of ultradistal radius and tibia and QCT and dual-energy x-ray absorptiometry (DXA) of lumbar spine were performed in 69 male AS patients (NY criteria). Spinal radiographs were assessed for vertebral fractures and syndesmophyte formation (mSASSS). The HRpQCT measurements were compared with the measurements of healthy controls.Results
The AS patients had lower cortical vBMD in radius (P = 0.004) and lower trabecular vBMD in tibia (P = 0.033), than did the controls. Strong correlations were found between trabecular vBMD in lumbar spine, radius (rS = 0.762; P < 0.001), and tibia (rS = 0.712; P < 0.001).When compared with age-matched AS controls, patients with vertebral fractures had lower lumbar cortical vBMD (-22%; P = 0.019), lower cortical cross-sectional area in radius (-28.3%; P = 0.001) and tibia (-24.0%; P = 0.013), and thinner cortical bone in radius (-28.3%; P = 0.001) and tibia (-26.9%; P = 0.016).mSASSS correlated negatively with trabecular vBMD in lumbar spine (rS = -0.620; P < 0.001), radius (rS = -0.400; p = 0.001) and tibia (rS = -0.475; p < 0.001) and also with trabecular thickness in radius (rS = -0.528; P < 0.001) and tibia (rS = -0.488; P < 0.001).Adjusted for age, syndesmophytes were significantly associated with decreasing trabecular vBMD, but increasing cortical vBMD in lumbar spine, but not with increasing cortical thickness or density in peripheral bone. Estimated lumbar vBMD by DXA correlated with trabecular vBMD measured by QCT (rS = 0.636; P < 0.001).Conclusions
Lumbar osteoporosis, syndesmophytes, and vertebral fractures were associated with both lower vBMD and deteriorated microarchitecture in peripheral bone. The results indicate that trabecular bone loss is general, whereas osteoproliferation is local in AS. 相似文献10.
Yoshimitsu Inoue Tomoko Ichinose-Kuwahara Chie Funaki Hiroyuki Ueda Yutaka Tochihara Narihiko Kondo 《Journal of physiological anthropology》2014,33(1):13
Purpose
The present study examined sex differences in the sweat gland response to acetylcholine (ACh) in physically trained and untrained male and female subjects.Methods
Sweating responses were induced on the forearm and thigh in resting subjects by ACh iontophoresis using a 10% solution at 2 mA for 5 min at 26°C and 50% relative humidity.Results
The ACh-induced sweating rate (SR) on the forearm and thigh was greater in physically trained male (P < 0.001 for the forearm and thigh, respectively) and female (P = 0.08 for the forearm, P < 0.001 for the thigh) subjects than in untrained subjects of both sexes. The SR was also significantly greater in physically trained males compared to females at both sites (P < 0.001) and in untrained males compared to females on the thigh (P < 0.02) only, although the degree of difference was greater in trained subjects than in untrained subjects. These sex differences can be attributed to the difference in sweat output per gland rather than the number of activated sweat glands.Conclusion
We conclude that physical training enhances the ACh-induced SR in both sexes but that the degree of enhancement is greater in male than in female subjects. The effects of physical training and sex on the SR may be due to changes in peripheral sensitivity to ACh and/or sweat gland size. 相似文献11.
Bimmer E.P.M. Claessen Wouter J. Kikkert Loes P. Hoebers Hassina Bahadurzada Marije M. Vis Jan Baan Karel T. Koch Robbert J. de Winter Jan G.P. Tijssen Jan J. Piek José P.S. Henriques 《Netherlands heart journal》2015,23(10):477-482
Background
The population is ageing rapidly and the proportion of patients aged ≥ 80 years undergoing primary percutaneous coronary intervention (PCI) is rising, but clinical trials have primarily been performed in younger patients.Methods
Patients undergoing primary PCI between 2003 and 2008 were subdivided into 3 groups: < 60, 60-79, and ≥ 80 years. Endpoints at 3-year follow-up included all-cause mortality, recurrent myocardial infarction (reMI), stent thrombosis, target lesion revascularisation (TLR), bleeding (BARC bleeding ≥ 3), stroke, and major adverse cardiovascular events (MACE, a composite of cardiac mortality, reMI, stroke and TLR).Results
2002 patients with ST-segment elevation myocardial infarction (STEMI) were included, 885 (44.2 %) aged < 60, 921 (46.0 %) 60–79, and 196 (9.7 %) ≥ 80 years. Comorbidities such as diabetes mellitus, prior stroke, malignant disease, anaemia, and chronic kidney disease were more prevalent in patients ≥ 80 years. The incidence of both ischaemic and bleeding events strongly increased with age. Age ≥ 80 years was an independent predictor of mortality (HR 2.56, 95 % CI1.69–3.87, p < 0.001), a borderline non-significant predictor of overall bleeding (HR 1.38, 95 %CI 0.95–2.00, p = 0.088), and a significant predictor of non-access site bleeding (HR 2.26, 95 %CI 1.46–3.51, p < 0.001).Conclusion
Patients ≥ 80 years experienced high rates of ischaemic and bleeding complications; especially in this high-risk patient group individualised therapy is needed to optimise clinical outcomes.Electronic Supplementary Material
The online version of this article (doi:10.1007/s12471-015-0733-2 contains supplementary material, which is available to authorized users. 相似文献12.
Christopher Uhlig Pedro L Silva Débora Ornellas Raquel S Santos Paulo J Miranda Peter M Spieth Thomas Kiss Michael Kasper B?rbel Wiedemann Thea Koch Marcelo M Morales Paolo Pelosi Marcelo Gama de Abreu Patricia RM Rocco 《Respiratory research》2014,15(1):56
Introduction
We investigated the effects of intravenous and intratracheal administration of salbutamol on lung morphology and function, expression of ion channels, aquaporin, and markers of inflammation, apoptosis, and alveolar epithelial/endothelial cell damage in experimental pulmonary (p) and extrapulmonary (exp) mild acute respiratory distress syndrome (ARDS).Methods
In this prospective randomized controlled experimental study, 56 male Wistar rats were randomly assigned to mild ARDS induced by either intratracheal (n = 28, ARDSp) or intraperitoneal (n = 28, ARDSexp) administration of E. coli lipopolysaccharide. Four animals with no lung injury served as controls (NI). After 24 hours, animals were anesthetized, mechanically ventilated in pressure-controlled mode with low tidal volume (6 mL/kg), and randomly assigned to receive salbutamol (SALB) or saline 0.9% (CTRL), intravenously (i.v., 10 μg/kg/h) or intratracheally (bolus, 25 μg). Salbutamol doses were targeted at an increase of ≈ 20% in heart rate. Hemodynamics, lung mechanics, and arterial blood gases were measured before and after (at 30 and 60 min) salbutamol administration. At the end of the experiment, lungs were extracted for analysis of lung histology and molecular biology analysis. Values are expressed as mean ± standard deviation, and fold changes relative to NI, CTRL vs. SALB.Results
The gene expression of ion channels and aquaporin was increased in mild ARDSp, but not ARDSexp. In ARDSp, intravenous salbutamol resulted in higher gene expression of alveolar epithelial sodium channel (0.20 ± 0.07 vs. 0.68 ± 0.24, p < 0.001), aquaporin-1 (0.44 ± 0.09 vs. 0.96 ± 0.12, p < 0.001) aquaporin-3 (0.31 ± 0.12 vs. 0.93 ± 0.20, p < 0.001), and Na-K-ATPase-α (0.39 ± 0.08 vs. 0.92 ± 0.12, p < 0.001), whereas intratracheal salbutamol increased the gene expression of aquaporin-1 (0.46 ± 0.11 vs. 0.92 ± 0.06, p < 0.001) and Na-K-ATPase-α (0.32 ± 0.07 vs. 0.58 ± 0.15, p < 0.001). In ARDSexp, the gene expression of ion channels and aquaporin was not influenced by salbutamol. Morphological and functional variables and edema formation were not affected by salbutamol in any of the ARDS groups, regardless of the route of administration.Conclusion
Salbutamol administration increased the expression of alveolar epithelial ion channels and aquaporin in mild ARDSp, but not ARDSexp, with no effects on lung morphology and function or edema formation. These results may contribute to explain the negative effects of β2-agonists on clinical outcome in ARDS. 相似文献13.
Purpose
Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in different cancer patients. The objective of this study was to investigate the clinical and prognostic value of preoperative plasma fibrinogen levels in patients with operable breast cancer.Methods
Two hundred and twenty-three patients diagnosed with breast cancer were retrospectively evaluated in this study. Plasma fibrinogen levels were examined before treatment and analyzed along with patient clinicopathological parameters, disease-free survival (DFS) and overall survival(OS). Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with DFS and OS.Results
Elevated preoperative plasma fibrinogen levels were directly associated with age of diagnose (≤47 vs. >47, p<0.001), menopause (yes vs. no, p<0.001), tumor size (T1&T2 vs.T3&T4, p = 0.033), tumor stage (Ⅰvs.Ⅱvs.Ⅲ, p = 0.034) and lymph node involvement (N = 0 vs. 1≤N≤3 vs. N≥4, p<0.001), but not with histological grade, molecular type and other Immunohistochemical parameters(ER, PR, HER2 and Ki-67). In a univariate survival analysis, tumor stage, tumor size, lymph node involvement (p<0.001/ p<0.001)and plasma fibrinogen (p<0.001/ p<0.001) levels were associated with disease-free and overall survival, but just lymph nodes involvement (p<0.001, hazard ratio [HR] = 2.9, 95% confidence interval [CI] = 1.6–5.3/ p = 0.006, HR = 3.2, 95% CI = 1.4–7.3) and plasma fibrinogen levels (p = 0.006, HR = 3.4, 95% CI = 1.4–8.3/ p = 0.002, HR = 10.1, 95% CI = 2.3–44.6) were associated with disease-free and overall survival in a multivariate survival analysis, respectively.Conclusions
This study demonstrates that elevated preoperative plasma fibrinogen levels are associated with breast cancer progression and are independently associated with a poor prognosis in patients with operable breast cancer. 相似文献14.
Maureen C Turina Nataliya Yeremenko Jacqueline E Paramarta Leen De Rycke Dominique Baeten 《Arthritis research & therapy》2014,16(4)
Introduction
Biomarkers complementing clinical evaluations may help to reduce the length and size of proof-of-concept (PoC) trials aimed to obtain quick “go/no go” decisions in the clinical development of new treatments. We aimed to identify and validate serum biomarkers with a high sensitivity to change upon effective treatment in spondyloarthritis (SpA) PoC trials.Methods
The candidate biomarkers high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), pentraxin-3 (PTX-3), alpha-2-macroglobulin (alpha-2-MG), matrix metalloproteinase-3 (MMP-3), calprotectin, and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay (ELISA) in healthy controls (n = 20) and SpA patients before and after 2 weeks of infliximab (n = 18) or placebo (n = 19) treatment in cohort 1. Clinical outcome was evaluated at week 12. Results were validated in ankylosing spondylitis (AS) with infliximab (cohort 2, n = 21) and peripheral SpA with etanercept (cohort 3, n = 20).Results
Serum levels of calprotectin, hs-CRP, PTX-3, VEGF (all P < 0.001) and MMP-3 (P = 0.062), but not IL-6 and alpha-2-MG, were increased in SpA versus healthy controls. Treatment with infliximab, but not placebo, significantly decreased calprotectin (P < 0.001) and hs-CRP (P < 0.001) levels, with a similar trend for MMP-3 (P = 0.063). The standardized response mean (SRM), which reflects the ability to detect changes over time, was high for calprotectin (−1.26), good for hs-CRP (−0.96) and moderate for MMP-3 (−0.52). Calprotectin and hs-CRP, but not MMP-3, were good biomarkers for treatment response in axial and peripheral SpA as evaluated and confirmed in cohort 2 and 3 respectively.Conclusions
Calprotectin and hs-CRP are good serum biomarkers with high sensitivity to change upon effective treatment at the group level in small-scale, short term PoC trials in SpA. 相似文献15.
Zhike Liang Qingling Zhang Catherine MR Thomas Kirandeep K Chana David Gibeon Peter J Barnes Kian Fan Chung Pankaj K Bhavsar Louise E Donnelly 《Respiratory research》2014,15(1):72
Background
Bacteria are frequently cultured from sputum samples of severe asthma patients suggesting a defect in bacterial clearance from the airway. We measured the capacity of macrophages from patients with asthma to phagocytose bacteria.Methods
Phagocytosis of fluorescently-labelled polystyrene beads, Haemophilus influenzae or Staphylococcus aureus by broncholaveolar lavage alveolar macrophages (AM) and by monocyte-derived macrophages (MDM) from non-asthmatics, mild-moderate and severe asthmatic patients was assessed using fluorimetry.Results
There were no differences in phagocytosis of polystyrene beads by AMs or MDMs from any of the subject groups. There was reduced phagocytosis of Haemophilus influenzae and Staphylococcus aureus in MDMs from patients with severe asthma compared to non-severe asthma (p < 0.05 and p < 0.01, respectively) and healthy subjects (p < 0.01and p < 0.001, respectively). Phagocytosis of Haemophilus influenzae and Staphylococcus aureus by AM was also reduced in severe asthma compared to normal subjects (p < 0.05). Dexamethasone and formoterol did not suppress phagocytosis of bacteria by MDMs from any of the groups.Conclusions
Persistence of bacteria in the lower airways may result partly from a reduced phagocytic capacity of macrophages for bacteria. This may contribute to increased exacerbations, airway colonization and persistence of inflammation. 相似文献16.
John E Davis Dale R Wagner Nathan Garvin David Moilanen Jessica Thorington Cory Schall 《Journal of physiological anthropology》2015,34(1)
Background
High-altitude inhabitants have cardiovascular and respiratory adaptations that are advantageous for high-altitude living, but they may have impaired cognitive function. This study evaluated the influence of altitude of residence on cognitive and psychomotor function upon acute exposure to very high altitude.Findings
Ecuadorians (31 residing at 0–1,500 m [LOW], 78 from 1,501–3,000 m [MOD], and 23 living >3,000 m [HIGH]) were tested upon their arrival to a hut at 4,860 m on Mount Chimborazo. Cognitive/psychomotor measurements included a go-no-go test (responding to a non-visual stimulus), a verbal fluency test (verbalizing a series of words specific to a particular category), and a hand movement test (rapidly repeating a series of hand positions). Mean differences between the three altitude groups on these cognitive/psychomotor tests were evaluated with one-way ANOVA. There were no significant differences (p = 0.168) between LOW, MOD, and HIGH for the verbal fluency test. However, the go-no-go test was significantly lower (p < 0.001) in the HIGH group (8.8 ± 1.40 correct responses) than the LOW (9.8 ± 0.61) or MOD (9.8 ± 0.55) groups, and both MOD (97.9 ± 31.2) and HIGH (83.5 ± 26.7) groups completed fewer correct hand movements than the LOW (136.6 ± 37.9) subjects (p < 0.001).Conclusions
Based on this field study, high-altitude residents appear to have some impaired cognitive function suggesting the possibility of maladaptation to long-term exposure to hypobaric hypoxia. 相似文献17.
Stefano Stagi Loredana Cavalli Carla Signorini Federico Bertini Marco Matucci Cerinic Maria Luisa Brandi Fernanda Falcini 《Arthritis research & therapy》2014,16(2):R83
Introduction
Our objective was to evaluate longitudinally the main bone-mass and quality predictors in young juvenile idiopathic arthritis (JIA) patients by using lumbar spine dual-energy X-ray absorptiometry (DXA) scan, radius peripheral quantitative computed tomography (pQCT), and phalangeal quantitative ultrasonography (QUS) at the same time.Methods
In total, 245 patients (172 females, 73 males; median age, 15.6 years: 148 oligoarticular, 55 polyarticular, 20 systemic, and 22 enthesitis-related-arthritis (ERA) onset) entered the study. Of these, 166 patients were evaluated longitudinally. Data were compared with two age- and sex-matched control groups.Results
In comparison with controls, JIA patients, but not with ERA, had a reduced spine bone-mineral apparent density (BMAD) standard deviation score (P < 0.001) and musculoskeletal deficits, with significantly lower levels of trabecular bone mineral density (TrabBMD) (P < 0.0001), muscle cross-sectional area (CSA) (P < 0.005), and density-weighted polar section modulus (SSIp) (P < 0.05). In contrast, JIA showed fat CSA significantly higher than controls (P < 0.0001). Finally, JIA patients had a significant reduced amplitude-dependent speed of sound (AD-SoS) (P < 0.001), and QUS z score (P < 0.005).Longitudinally, we did not find any difference in all JIA patients in comparison with baseline, except for the SSIp value that normalized. Analyzing the treatments, a significant negative correlation among spine BMAD values, TrabBMD, AD-SoS, and systemic and/or intraarticular corticosteroids, and a positive correlation among TNF-α-blocking agents and spine BMAD, TrabBMD, and AD-SoS were observed.Conclusions
JIA patients have a low bone mass that, after a first increase due to the therapy, does not reach the normal condition over time. The pronounced bone deficits in JIA are greater than would be expected because of reduction in muscle cross-sectional area. Thus, bone alterations in JIA likely represent a mixed defect of bone accrual and lower muscle forces. 相似文献18.
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Limin Wu Joon Yong Chung Tian Cao Gina Jin William J. Edmiston III Suzanne Hickman Emily S. Levy Jordyn A. Whalen Eliza Sophie LaRovere Abrams Alexei Degterev Eng H. Lo Lorenzo Tozzi David L. Kaplan Joseph El Khoury Michael J. Whalen 《Cell death & disease》2021,12(11)
Traumatic brain injury (TBI) is a leading cause of death and disability with no specific effective therapy, in part because disease driving mechanisms remain to be elucidated. Receptor interacting protein kinases (RIPKs) are serine/threonine kinases that assemble multi-molecular complexes that induce apoptosis, necroptosis, inflammasome and nuclear factor kappa B activation. Prior studies using pharmacological inhibitors implicated necroptosis in the pathogenesis of TBI and stroke, but these studies cannot be used to conclusively demonstrate a role for necroptosis because of the possibility of off target effects. Using a model of cerebral contusion and RIPK3 and mixed lineage kinase like knockout (MLKL−/−) mice, we found evidence for activation of RIPK3 and MLKL and assembly of a RIPK1-RIPK3-MLKL necrosome complex in pericontusional brain tissue. Phosphorylated forms of RIPK3 and MLKL were detected in endothelium, CD11b + immune cells, and neurons, and RIPK3 was upregulated and activated in three-dimensional human endothelial cell cultures subjected to CCI. RIPK3−/− and MLKL−/− mice had reduced blood-brain barrier damage at 24 h (p < 0.05), but no differences in neuronal death (6 h, p = ns in CA1, CA3 and DG), brain edema (24 h, p = ns), or lesion size (4 weeks, p = ns) after CCI. RIPK3−/−, but not MLKL−/− mice, were protected against postinjury motor and cognitive deficits at 1–4 weeks (RIPK3−/− vs WT: p < 0.05 for group in wire grip, Morris water maze hidden platform trials, p < 0.05 for novel object recognition test, p < 0.01 for rotarod test). RIPK3−/− mice had reduced infiltrating leukocytes (p < 0.05 vs WT in CD11b + cells, microglia and macrophages), HMGB1 release and interleukin-1 beta activation at 24–48 h (p < 0.01) after CCI. Our data indicate that RIPK3 contributes to functional outcome after cerebral contusion by mechanisms involving inflammation but independent of necroptosis.Subject terms: Molecular neuroscience, Brain injuries 相似文献
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M. Martínez-Sellés E. Pérez-David R. Yotti J. Jiménez-Borreguero G. Loughlin L. Gallego A. Ayesta M.J. Olivera J. Bermejo F. Fernández-Avilés 《Netherlands heart journal》2015,23(12):578-584