187 research outputs found

    JNK inhibition reduces lung remodeling and pulmonary fibrotic systemic markers

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    Education as a moderator of middle-age cardiovascular risk factor-old-age cognition relationships: testing cognitive reserve hypothesis in epidemiological study

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    Background: higher educational attainment and less midlife cardiovascular risk factors are related to better old-age cognition. Whether education moderates the association between cardiovascular risk factors and late-life cognition is not known. We studied if higher education provides resilience against the deteriorative effects of higher middle-age body mass index (BMI) and a combination of midlife cardiovascular risk factors on old-age cognition.Methods: the study population is the older Finnish Twin Cohort (n = 4,051, mean age [standard deviation, SD] = 45.5 years [6.5]). Cardiovascular risk factors and education were studied at baseline with questionnaires in 1975, 1981 and/or 1990 (participation rates of 89, 84 and 77%, respectively). Cognition was evaluated with telephone interviews (participation rate 67%, mean age [SD] =73.4 [2.9] years, mean follow-up [SD] = 27.8 [6.0] years) in 1999-2017. We studied the main and interactive effects of education and BMI/dementia risk score on late-life cognition with linear regression analysis. The study design was formulated before the pre-defined analyses.Results: years of education moderated the association between BMI with old-age cognition (among less educated persons, BMI-cognition association was stronger [B = -0.24 points per BMI unit, 95% CI -0.31, -0.18] than among more educated persons [B = -0.06 points per BMI unit, 95% CI -0.16, 0.03], Pinteraction Conclusions: our results support the cognitive reserve hypothesis. Those with higher education may tolerate the deteriorative effects of midlife cardiovascular risk factors on old-age cognition better than those with lower education.</p

    Changes of Alpha1-Antitrypsin Levels in Allergen-induced Nasal Inflammation

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    ObjectivesAlpha1-antitrypsin (AAT) is the main inhibitor of human neutrophil elastase, and plays a role in counteracting the tissue damage caused by elastase in local inflammatory conditions. The study evaluated the involvement of AAT in nasal allergic inflammation.MethodsForty subjects with mono-sensitization to Dermatophagoides pteronyssinus (Dpt) were enrolled. Twenty allergic rhinitis patients frequently complained of nasal symptoms such as rhinorrhea, stuffiness, sneezing, and showed positive responses to the nasal provocation test (NPT) with Dpt (Group I). The other 20 asymptomatic patients showed sensitization to Dpt but negative NPT (Group II). The levels of AAT, eosinophil cationic protein (ECP), and Dpt-specific IgA antibodies were measured in the nasal lavage fluids (NLFs), collected at baseline, 10 minutes, 30 minutes, 3 hours, and 6 hours after the NPT. Nasal mucosa AAT expression was evaluated with immunohistochemical staining from Group I and Group II.ResultsAt baseline, only the Dpt-specific IgA level was significantly increased in the NLFs of Group I compared with Group II, while ECP and AAT levels were not significantly different between two groups. After Dpt provocation, AAT, ECP, and Dpt-specific IgA levels were significantly increased in the NLFs of Group I during the early and late responses. The protein expression level of AAT was mostly found in the infiltrating inflammatory cells of the nasal mucosa, which was significantly increased in Group I compared to Group II.ConclusionThe increment of AAT showed a close relationship with the activation of eosinophils induced by allergen-specific IgA in the NLFs of patients with allergic rhinitis after allergen stimulation. These findings implicate AAT in allergen-induced nasal inflammation

    Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy : a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and H-1-MR spectroscopy compared with histology (subgroup in the RAXO trial)

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    Background: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. Patients and methods: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusionweighted imaging and H-1-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and KaplaneMeier estimates of overall survival (OS). Results: In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). H-1-MRS revealed steatohepatosis induced by systemic therapy. Conclusions: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.Peer reviewe

    Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy : a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and H-1-MR spectroscopy compared with histology (subgroup in the RAXO trial)

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    Background: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. Patients and methods: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusionweighted imaging and H-1-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and KaplaneMeier estimates of overall survival (OS). Results: In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). H-1-MRS revealed steatohepatosis induced by systemic therapy. Conclusions: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.Peer reviewe

    Evaluation of HER-2/neu gene amplification and protein expression in non-small cell lung carcinomas

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    HER-2/neu gene amplification and cell surface overexpression are important factors in breast cancer for prognosis and prediction of sensitivity to anti-HER-2/neu monoclonal antibody therapy. In lung cancer, the clinical significance of HER-2/neu expression is currently under evaluation. We investigated 238 non-small lung carcinomas for HER-2/neu protein overexpression by immunohistochemistry using the HercepTest. We found 2+ or 3+ overexpression in 39 patients (16%), including 35% in adenocarcinomas and 20% in large cell carcinomas, but only 1% of squamous cell carcinomas. Marked (3+) overexpression was uncommon (4%). The association between protein expression and gene copy number per cell, as determined by fluorescence in situ hybridisation assay, was investigated in 51 of these NSCLC tumours. Twenty-seven tumours (53%) were negative by both tests. Marked (3+) protein expression and gene amplification were present in only 4% of samples. In 11 tumours (21%), gene gain was accompanied by chromosomal aneusomy and did not result in high protein levels while in 7 (14%) the score 2+ was associated with maximum number of signals per cell <9. The prognostic implication of HER-2/neu protein expression was studied in 187 surgically resected tumours. No statistical difference in survival was observed comparing patients with positive (2+/3+) and negative tumours (0/1+), although 3+ patients showed a tendency to shorter survival. The therapeutic implications of protein expression and gene amplification in lung cancer need to be examined in prospective clinical trials

    Amphiphilic superabsorbent cellulose nanofibril aerogels

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    Ultra-light (1.7 to 8.1 mg cm-3) and ultra-porous (99.5 to 99.9%) aerogels have been assembled from cellulose nanofibrils (CNFs) that were defibrillated from rice straw cellulose at 96.8% yield. The as-prepared aerogels, amphiphilic super-absorbents, absorbing 210 and 375 times water and chloroform, respectively, are far superior to any previously reported cellulose aerogel. Vapor deposition with triethoxyl(octyl) silane turned the amphiphilic aerogel more hydrophobic and oleophilic, capable of absorbing 139-356 times non-polar hydrocarbons, polar aprotic solvents and oils, surpassing all previously reported polymeric, cellulosic and carbonaceous aerogels by 2 to nearly 20 times. These aerogels are excellent amphiphilic super-absorbents for selective oil removal and recovery. This journal is © the Partner Organisations 2014

    Breast MRI: guidelines from the European Society of Breast Imaging

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    The aim of breast MRI is to obtain a reliable evaluation of any lesion within the breast. It is currently always used as an adjunct to the standard diagnostic procedures of the breast, i.e., clinical examination, mammography and ultrasound. Whereas the sensitivity of breast MRI is usually very high, specificity—as in all breast imaging modalities—depends on many factors such as reader expertise, use of adequate techniques and composition of the patient cohorts. Since breast MRI will always yield MR-only visible questionable lesions that require an MR-guided intervention for clarification, MRI should only be offered by institutions that can also offer a MRI-guided breast biopsy or that are in close contact with a site that can perform this type of biopsy for them. Radiologists involved in breast imaging should ensure that they have a thorough knowledge of the MRI techniques that are necessary for breast imaging, that they know how to evaluate a breast MRI using the ACR BI-RADS MRI lexicon, and most important, when to perform breast MRI. This manuscript provides guidelines on the current best practice for the use of breast MRI, and the methods to be used, from the European Society of Breast Imaging (EUSOBI)
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