The E3 ubiquitin ligase adaptor speckle-type POZ protein (SPOP) is frequently dysregulated in prostate adenocarcinoma (PC), via either somatic mutations or mRNA downregulation, suggesting an ...important tumour suppressor function. To examine its physiologic role in the prostate epithelium in vivo, we generated mice with prostate-specific biallelic ablation of Spop. These mice exhibited increased prostate mass, prostate epithelial cell proliferation, and expression of c-MYC protein compared to littermate controls, and eventually developed prostatic intraepithelial neoplasia (PIN). We found that SPOP
can physically interact with c-MYC protein and, upon exogenous expression in vitro, can promote c-MYC ubiquitination and degradation. This effect was attenuated in PC cells by introducing PC-associated SPOP mutants or upon knockdown of SPOP via short-hairpin-RNA, suggesting that SPOP inactivation directly increases c-MYC protein levels. Gene Set Enrichment Analysis revealed enrichment of Myc-induced genes in transcriptomic signatures associated with SPOP
. Likewise, we observed strong inverse correlation between c-MYC activity and SPOP mRNA levels in two independent PC patient cohorts. The core SPOP
;MYC
transcriptomic response, defined by the overlap between the SPOP
and c-MYC transcriptomic programmes, was also associated with inferior clinical outcome in human PCs. Finally, the organoid-forming capacity of Spop-null murine prostate cells was more sensitive to c-MYC inhibition than that of Spop-WT cells, suggesting that c-MYC upregulation functionally contributes to the proliferative phenotype of Spop knock-out prostates. Taken together, our data highlight SPOP as an important regulator of luminal epithelial cell proliferation and c-MYC expression in prostate physiology, identify c-MYC as a novel bona fide SPOP substrate, and help explain the frequent inactivation of SPOP in human PC. We propose SPOP
-induced stabilization of c-MYC protein as a novel mechanism that can increase total c-MYC levels in PC cells, in addition to amplification of c-MYC locus.
Introduction and objectives
Thoracic ultrasound (TUS) has been established as a powerful diagnostic and monitoring tool in the Intensive Care Unit (ICU). However, studies outside the critical care ...setting are scarce. The aim of this study was to investigate the value of TUS for hospitalized or ambulatory community patients.
Materials and methods
This was a retrospective study conducted from 2016 to 2020 in the TUS clinic at Heraklion University Hospital. TUS examination was performed using a standard ultrasound machine (EUB HITACHI 8500), and a high-frequency microconvex probe (5–8 MHz). Patients had been referred by their primary physician to address a range of different questions. The various respiratory system entities were characterised according to internationally established criteria.
Results
762 TUS studies were performed on 526 patients due to underlying malignancy (
n
= 376), unexplained symptoms/signs (
n
= 53), pregnancy related issues (
n
= 42), evaluation of abnormal findings in X-ray (
n
= 165), recent surgery/trauma (
n
= 23), recent onset respiratory failure (
n
= 12), acute respiratory infection (
n
= 66) and underlying non-malignant disease (
n
= 25). Pleural effusion was the commonest pathologic entity (
n
= 610), followed by consolidation (
n
= 269), diaphragmatic dysfunction/paradox (
n
= 174) and interstitial syndrome (
n
= 53). Discrepancies between chest X-ray and ultrasonographic findings were demonstrated in 96 cases. The TUS findings guided invasive therapeutic management in 448 cases and non-invasive management in 43 cases, while follow-up monitoring was decided in 271 cases.
Conclusions
This study showed that TUS can identify the most common respiratory pathologic entities encountered in hospitalized and community ambulatory patients, and is especially useful in guiding the decision making process in a diverse group of patients.
Purpose
There is limited data regarding the sleep quality in survivors of critical illness, while the time course of the sleep abnormalities observed after ICU discharge is not known. The aim of this ...study was to assess sleep quality and the time course of sleep abnormalities in survivors of critical illness.
Methods
Eligible survivors of critical illness without hypercapnia and hypoxemia were evaluated within 10 days (1st evaluation,
n
= 36) and at 6 months after hospital discharge (2nd evaluation,
n
= 29). At each visit, all patients underwent an overnight full polysomnography and completed health-related quality of life questionnaires (HRQL). Lung function and electro-diagnostic tests (ED) were performed in 24 and 11 patients, respectively.
Results
At 1st evaluation, sleep quality and HRQL were poor. Sleep was characterised by high percentages of N1, low of N3 and REM stages, and high apnea–hypopnea index (AHI, events/h). Twenty-two out of 36 patients (61%) exhibited AHI ≥ 15 (21 obstructive, 1 central). None of the patients’ characteristics, including HRQL and lung function, predicted the occurrence of AHI ≥ 15. At 6 months, although sleep quality remained poor (high percentages of N1 and low of REM), sleep architecture had improved as indicated by the significant increase in N3 4.2% (0–12.5) vs. 9.8% (3.0–20.4) and decrease in AHI 21.5 (6.5–29.4) vs. 12.8 (4.7–20.4). HRQL improved slightly but significantly at 6 months. Neither the changes in HRQL nor in lung function tests were related to these of sleep architecture. Six out of eight patients with abnormal ED at 1st evaluation continued to exhibit abnormal results at 6 months.
Conclusions
Survivors of critical illness exhibited a high prevalence of obstructive sleep-disordered breathing and poor sleep architecture at hospital discharge, which slightly improved 6 months later, indicating that reversible factors are partly responsible for these abnormalities.
One of the most significant changes in modern healthcare delivery has been the evolution of the paper record to the electronic health record (EHR). Despite incentives that provide reimbursements to ...hospitals and healthcare providers for adopting EHR technology, there is a large number of barriers that preclude its implementation. EHR has a great impact on a variety of healthcare outcomes, mainly favoring its use. Consequently, the development of effective implementation strategies is essential in modern healthcare society.
Abstract
Introduction:
To assess the role of different levels of compliance and long-term effects of PAP therapy on gas exchange, sleepiness, quality of life, depression and death rate in patients ...with OHS.
Methods:
Two hundred fifty two patients with newly diagnosed OHS, who have been recommended PAP therapy, were followed up for a minimum of 2 years. Arterial blood samples were taken for gas level measurements with patients awake, for more than 4 h since wakening. The hours/day and percentage of days PAP was used were monitored. Epworth sleepiness scale (ESS), quality of life (Short Form 36-SF-36) and Beck Depression Inventory (BDI) were recorded together with the death rate before and at the end of the follow up period.
Results:
At the end of the follow-up period (mean duration, 42 months), PaO2 had increased from baseline (p<0.001), and both PaCO2 and HCO3− had decreased (p<0.001). PAP therapy also significantly improved ESS (p<0.001), BDI (p<0.001) and SF-36 (p<0.001) scores. During follow-up, 11 patients died (2 due to progression of respiratory failure). Patients who used PAP therapy for > 6 hours/day had a considerably greater improvement in blood gases and questionnaires scores than less adherent patients.
Conclusion:
Increased hours of use and long-term therapy with PAP are effective in the treatment of patients with OHS. Clinicians should encourage adherence to PAP therapy in order to provide a significant improvement in clinical status and gas exchange in these patients.
Support (If Any):
None.
Obstructive sleep apnea in pulmonary fibrosis Schiza, Sophia E; Bouloukaki, Izolde; Bolaki, Maria ...
Current opinion in pulmonary medicine,
2020-September, 2020-09-00, 20200901, Letnik:
26, Številka:
5
Journal Article
PURPOSE OF REVIEWIn previous years, there was limited research related to the role of sleep in interstitial lung diseases (ILDs). Physicians treating ILD patients tended to focus mainly on the daily ...disabling symptoms overlooking the possible significant role of coexisting sleep disorders, such as obstructive sleep apnea (OSA). However, recently, there has been a growing interest in OSA in ILDs, as well as OSA effect on sleep, life quality and outcome in these patients with emphasis on idiopathic pulmonary fibrosis (IPF).
RECENT FINDINGSOSA has been recognized as an important, high-prevalence comorbidity for the diagnosis and management of IPF. This publication provides a summary of the most relevant recent evidence with regard to OSA in various ILDs and especially IPF, including prevalence, clinical presentation, complications, screening and diagnosis. It also provides updated evidence on the role of OSA therapy in improving sleep, quality of life and disease outcome.
SUMMARYIt is too early to characterize OSA and ILDs association as an ‘overlap’ syndrome. In depth research is needed, including studies with large numbers of ILDs and IPF patients. The main priority is to increase the awareness among physicians for early diagnosis of OSA in ILDs patients.
In this study, we sought to assess the validity of lung ultrasound (LUS) during the follow-up of patients with a wide spectrum of interstitial lung diseases (ILDs).
Twenty-four patients (13 males, 11 ...females; mean age ± SD, 65.4 ± 14.3 years; age range, 40-84 years) with a diagnosis of ILDs who were admitted to the Interstitial Lung Disease Unit were prospectively enrolled. Patients were examined with a 56-lung intercostal space LUS protocol in lateral decubitus position, at baseline, 6-months, and 1-year. The LUS score was defined as the sum of B-lines counted in each intercostal space. All patients underwent complete pulmonary function tests at baseline and follow-up time-points. High-resolution computed tomography (HRCT) was performed at baseline and during follow-up, according to personalized patients' needs. All HRCT studies were graded according to the Warrick scoring system (WS).
Pooled data analysis showed a significant correlation between WS and LUS scores (P < .001). For separate time-point analysis, a significant correlation between LUS scores and WS was found at baseline (P < .001) and 1 year (P = .005). LUS scores negatively correlated with alveolar volume (VA) (P < .046) and diffusing capacity for carbon monoxide (DLCO) (P < .001) at 6 months and with transfer coefficient of the lung for carbon monoxide (KCO) (P < .031) and DLCO (P = .002) at 12-months. A multivariate regression model showed DLCO to be an independent predictor of LUS score at 1 year (P = .026).
Our results highlight the validity and potential applicability of LUS for disease monitoring in a wide spectrum of ILDs.
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