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Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Methods

In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6?months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI).

Results

After 1?month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6?months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r?=??0.5376; P?<?.001 and r?=??0.3285; P?<?.001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β?=??0.57, P?=?.019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581–0.863]; P?=?.029) were used as classifier, especially in the first 2?months of treatment (0.806 [95% CI 0.665–0.947]; P?<?.001).

Conclusions

This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy.  相似文献   
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PURPOSE: The purpose of this study was to compare the dentin/adhesive interfacial characteristics when bonding to noncarious as well as caries-affected dentin. MATERIALS AND METHODS: Seven extracted, unerupted, third molars were sectioned into halves. Artificial caries was created on one-half of each tooth, leaving the other half as a control. Dentin surfaces were treated with UNO adhesive according to the manufacturer's instructions for the wet-bonding technique and under environmental conditions present in the oral cavity. Dentin/adhesive interface sections of each half-tooth were stained with Goldner's trichrome, a classic bone stain, and examined using light microscopy. The width of exposed collagen was measured directly from photomicrographs, and adhesive penetration was analyzed qualitatively. RESULTS: The degree and extent to which the adhesive encapsulated the demineralized dentin matrix were reflected in the color difference in the stained sections with the noncarious dentin sections showing a degree of collagen encapsulation superior to that of the caries-affected dentin sections. The overall mean widths of exposed collagen were significantly (p < or = .05) greater at the caries-affected dentin/adhesive interface, 8.6 (1.7) microm, as compared with those at the noncarious dentin/adhesive interface, 6.0 (1.5) microm. CONCLUSIONS: The morphologic characteristics of the caries-affected dentin/interface suggest an increase in the exposed collagen zone and a decrease in the quality of the adhesive infiltration when compared with noncarious dentin. The evidence suggests that dentin substrate characteristics have a significant effect on the dentin/adhesive interface structure.  相似文献   
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BACKGROUND: Little is known about the health-related quality of life (HRQOL) of nonclinical samples of people with irritable bowel syndrome (IBS) in Canada. In a pilot survey, the impact of IBS on HRQOL using a population-based, urban sample was examined. METHODS: A random sample of Calgary residents (18 years of age or older), selected by random digit dialing (n=1521), completed a structured questionnaire including ROME II Criteria and Medical Outcomes Study Short-Form 12-Item Health Survey, version 2 (SF-12v2). The mean scale and summary scores of SF-12v2 for those who did and did not meet ROME II criteria and for those who met ROME II criteria with and without visiting a physician in past three months were determined and compared using multiple regression analyses. RESULTS: Of the 951 households successfully contacted, 590 (62%) were willing to participate, of which 437 (74%) individuals were recruited. One hundred ten IBS cases (81 of which were women) and 327 non-IBS controls (180 of which were women) were identified. All of the eight mean scale scores and the two mean summary scores were significantly lower in people with IBS than in those without, whether or not adjusting for demographics. Forty-four of the 110 IBS cases (40%) sought medical help. Significantly lower mean physical component score and three scale scores (general health, social functioning and role physical) were found in those who sought medical help than in those who did not. CONCLUSIONS: People with IBS experience significant impairment in HRQOL, including both physical and mental well-being. People with IBS who seek medical help report worse physical health than those who do not, but their mental health is no different.  相似文献   
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