Abnormal airway smooth muscle function can contribute to cystic fibrosis (CF) airway disease. We previously found that airway smooth muscle from newborn CF pigs had increased basal tone, an increased ...bronchodilator response, and abnormal calcium handling. Since CF pigs lack airway infection and inflammation at birth, these findings suggest intrinsic airway smooth muscle dysfunction in CF. In this study, we tested the hypothesis that CFTR loss in airway smooth muscle would produce a distinct set of changes in the airway smooth muscle transcriptome that we could use to develop novel therapeutic targets. Total RNA sequencing of newborn wild-type and CF airway smooth muscle revealed changes in muscle contraction-related genes, ontologies, and pathways. Using connectivity mapping, we identified several small molecules that elicit transcriptional signatures opposite of CF airway smooth muscle, including NVP-TAE684, an inhibitor of proline-rich tyrosine kinase 2 (PYK2). In CF airway smooth muscle tissue, PYK2 phosphorylation was increased and PYK2 inhibition decreased smooth muscle contraction. In vivo NVP-TAE684 treatment of wild-type mice reduced methacholine-induced airway smooth muscle contraction. These findings suggest that studies in the newborn CF pig may provide an important approach to enhance our understanding of airway smooth muscle biology and for discovery of novel airway smooth muscle therapeutics for CF and other diseases of airway hyperreactivity.
This paper presents an analysis of infinite phased arrays of aperture-coupled two-layer dual-patch microstrip antennas. The substrate layers for supporting the patches have the same dielectric ...constant and are separated by an airgap. The numerical model is based on the spectral-domain method of moments together with the Floquet theorem. Calculated results predict a 2:1 standing-wave ratio (SWR) bandwidth of 30-40% in a /spl plusmn/60/spl deg/ scan cone for arrays operating at around 4 GHz. Measured results from a waveguide simulator are obtained to verify the theoretical prediction.
Objective
To evaluate the effectiveness of small‐group nurse‐administered cognitive behavioural therapy for insomnia (CBTI) as an early intervention of mood disorders with comorbid insomnia.
Methods
...A total of 200 patients with first‐episode depressive or bipolar disorders and comorbid insomnia were randomized in a ratio of 1:1 to receiving 4‐session CBTI or not in a routine psychiatric care setting. Primary outcome was Insomnia Severity Index. Secondary outcomes included response and remission status; daytime symptomatology and quality of life; medication burden; sleep‐related cognitions and behaviours; and the credibility, satisfaction, adherence and adverse events of CBTI. Assessments were conducted at baseline, 3, 6, and 12‐month.
Results
Only a significant time‐effect but no group‐by‐time interaction was found in the primary outcome. Several secondary outcomes had significantly greater improvements in CBTI group, including higher depression remission at 12‐month (59.7% vs. 37.9%, χ2 = 6.57, p = .01), lower anxiolytic use at 3‐month (18.1% vs. 33.3%, χ2 = 4.72, p = .03) and 12‐month (12.5% vs. 25.8%, χ2 = 3.26, p = .047), and lesser sleep‐related dysfunctional cognitions at 3 and 6‐month (mixed‐effects model, F = 5.12, p = .001 and .03, respectively). Depression remission rate was 28.6%, 40.3%, and 59.7% at 3, 6, and 12‐month, respectively in CBTI group and 28.4%, 31.1%, and 37.9%, respectively in no CBTI group.
Conclusion
CBTI may be a useful early intervention to enhance depression remission and reduce medication burden in patients with first‐episode depressive disorder and comorbid insomnia.
This randomised trial showed that en bloc resection of the bladder tumour (ERBT) led to a significant reduction in the 1-yr recurrence rate in patients with non–muscle-invasive bladder cancer. With ...superiority in treatment efficacy, our study provided the best evidence to support ERBT as the first-line surgical treatment for patients with bladder tumours of ≤3 cm. The multicentre setting also showed that ERBT is generalisable with a comparable safety profile to standard resection.
Conventionally, standard resection (SR) is performed by resecting the bladder tumour in a piecemeal manner. En bloc resection of the bladder tumour (ERBT) has been proposed as an alternative technique in treating non–muscle-invasive bladder cancer (NMIBC).
To investigate whether ERBT could improve the 1-yr recurrence rate of NMIBC, as compared with SR.
A multicentre, randomised, phase 3 trial was conducted in Hong Kong. Adults with bladder tumour(s) of ≤3 cm were enrolled from April 2017 to December 2020, and followed up until 1 yr after surgery.
Patients were randomly assigned to receive either ERBT or SR in a 1:1 ratio.
The primary outcome was 1-yr recurrence rate. A modified intention-to-treat analysis on patients with histologically confirmed NMIBC was performed. The main secondary outcomes included detrusor muscle sampling rate, operative time, hospital stay, 30-d complications, any residual or upstaging of disease upon second-look transurethral resection, and 1-yr progression rate.
A total of 350 patients underwent randomisation, and 276 patients were histologically confirmed to have NMIBC. At 1 yr, 31 patients in the ERBT group and 46 in the SR group developed recurrence; the Kaplan-Meier estimate of 1-yr recurrence rates were 29% (95% confidence interval, 18–37) in the ERBT group and 38% (95% confidence interval, 28–46) in the SR group (p = 0.007). Upon a subgroup analysis, patients with 1–3 cm tumour, single tumour, Ta disease, or intermediate-risk NMIBC had a significant benefit from ERBT. None of the patients in the ERBT group and three patients in the SR group developed progression to muscle-invasive bladder cancer; the Kaplan-Meier estimates of 1-yr progression rates were 0% in the ERBT group and 2.6% (95% confidence interval, 0–5.5) in the SR group (p = 0.065). The median operative time was 28 min (interquartile range, 20–45) in the ERBT group and 22 min (interquartile range, 15–30) in the SR group (p < 0.001). All other secondary outcomes were similar in the two groups.
In patients with NMIBC of ≤3 cm, ERBT resulted in a significant reduction in the 1-yr recurrence rate when compared with SR (funded by GRF/ECS, RGC, reference no.: 24116518; ClinicalTrials.gov number, NCT02993211).
Conventionally, non–muscle-invasive bladder cancer is treated by resecting the bladder tumour in a piecemeal manner. In this study, we found that en bloc resection, that is, removal of the bladder tumour in one piece, could reduce the 1-yr recurrence rate of non–muscle-invasive bladder cancer.
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