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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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A 20-month-old Kuwaiti girl had manifestations of lipoid proteinosis, a rare autosomal recessive disorder seen more commonly in Caucasians. This condition is diagnosed based on clinical, histopathologic, and ultrastructural criteria. Its biochemical and genetic aspects are still poorly understood.  相似文献   
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The present study sought to investigate the moderating function that social problem-solving effectiveness serves in relation to negative stressful life events and depressive symptomatology. It was also hypothesized that knowledge of problem solving would improve upon the prediction of level of depressive symptoms beyond the assessment of stressful events. Results involving 462 undergraduate students provide support for both predictions. Specifically, findings from a multiple regression analysis indicated that (1) differences in reported depressive mood between subjects under high and low stress levels were minimal for individuals characterized as effective problem-solvers, relative to those persons with problem-solving scores reflective of ineffective problem solving; and (2) assessment of problem-solving scores and their interaction with stress level provided for an additional three times the amount of explained variance in predicting depression scores beyond life stress scores. Additionally, a cross-validation of the regression analysis was conducted and found to result in a minimal amount of shrinkage that could be due to samplespecific characteristics.We would like to extend our appreciation to two anonymous reviewers for their helpful comments on an earlier draft of this article. The study was supported in part by a grant funded by Fairleigh Dickinson University to the first author.  相似文献   
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This paper presents some of the findings from the Smoking in Pregnancy study of attitudes towards smoking among pregnant women, mothers of young children and their partners in East Surrey. As part of the study, respondents completed a General Health Questionnaire to identify mental health difficulties and, if they were smoking at the time of the study, they also completed the Fagerstrom nicotine addiction test. Eleven female respondents had high scores on the General Health Questionnaire, suggesting symptoms of depression, anxiety and/or social dysfunction for these women. There was no evidence that smokers were suffering from greater mental health difficulties than ex-smokers or non-smokers. However, the General Health Questionnaire scores of smokers were positively associated with their level of nicotine dependence. Furthermore, when General Health Questionnaire scores of all respondents were compared with self-reported health status there was a marked discrepancy suggesting under-reporting of symptoms by women.  相似文献   
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Computer technology has made it possible significantly to improve the technique and interpretation of the micturitional urethral pressure profile (MUPP). Thirty-nine patients with lower urinary tract symptoms have been investigated by this technique and the results compared with those of standard pressure/flow studies. A good correlation was found between the two methods of diagnosing outflow obstruction, but micturitional urethral pressure profiles offered practical advantages in patients who were elderly, immobile or who had severe involuntary voiding, and diagnostic advantages in patients with absent or poor detrusor contractility and those with equivocal pressure/flow studies.  相似文献   
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