The different clinical faces of obstructive sleep apnoea: a cluster analysis.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageAlthough commonly observed in clinical practice, the heterogeneity of obstructive sleep apnoea (OSA) clinical presentation has not been formally characterised. This study was the first to apply cluster analysis to identify subtypes of patients with OSA who experience distinct combinations of symptoms and comorbidities. An analysis of baseline data from the Icelandic Sleep Apnoea Cohort (822 patients with newly diagnosed moderate-to-severe OSA) was performed. Three distinct clusters were identified. They were classified as the "disturbed sleep group" (cluster 1), "minimally symptomatic group" (cluster 2) and "excessive daytime sleepiness group" (cluster 3), consisting of 32.7%, 24.7% and 42.6% of the entire cohort, respectively. The probabilities of having comorbid hypertension and cardiovascular disease were highest in cluster 2 but lowest in cluster 3. The clusters did not differ significantly in terms of sex, body mass index or apnoea-hypopnoea index. Patients with OSA have different patterns of clinical presentation, which need to be communicated to both the lay public and the professional community with the goal of facilitating care-seeking and early identification of OSA. Identifying distinct clinical profiles of OSA creates a foundation for offering more personalised therapies in the future

Structural Basis of Competitive Recognition of p53 and MDM2 by HAUSP/USP7: Implications for the Regulation of the p53–MDM2 Pathway

Herpesvirus-associated ubiquitin-specific protease (HAUSP, also known as USP7), a deubiquitylating enzyme of the ubiquitin-specific processing protease family, specifically deubiquitylates both p53 and MDM2, hence playing an important yet enigmatic role in the p53–MDM2 pathway. Here we demonstrate that both p53 and MDM2 specifically recognize the N-terminal tumor necrosis factor–receptor associated factor (TRAF)–like domain of HAUSP in a mutually exclusive manner. HAUSP preferentially forms a stable HAUSP–MDM2 complex even in the presence of excess p53. The HAUSP-binding elements were mapped to a peptide fragment in the carboxy-terminus of p53 and to a short-peptide region preceding the acidic domain of MDM2. The crystal structures of the HAUSP TRAF-like domain in complex with p53 and MDM2 peptides, determined at 2.3-Å and 1.7-Å resolutions, respectively, reveal that the MDM2 peptide recognizes the same surface groove in HAUSP as that recognized by p53 but mediates more extensive interactions. Structural comparison led to the identification of a consensus peptide-recognition sequence by HAUSP. These results, together with the structure of a combined substrate-binding-and-deubiquitylation domain of HAUSP, provide important insights into regulation of the p53–MDM2 pathway by HAUSP

Electric-Field-Induced Connectivity Switching in Single-Molecule Junctions

Summary(#br)The manipulation of molecule-electrode interaction is essential for the fabrication of molecular devices and determines the connectivity from electrodes to molecular components. Although the connectivity of molecular devices could be controlled by molecular design to place anchor groups in different positions of molecule backbones, the reversible switching of such connectivities remains challenging. Here, we develop an electric-field-induced strategy to switch the connectivity of single-molecule junctions reversibly, leading to the manipulation of different connectivities in the same molecular backbone. Our results offer a new concept of single-molecule manipulation and provide a feasible strategy to regulate molecule-electrode interaction

Spousal involvement and CPAP adherence: A dyadic perspective

Poor adherence to continuous positive airway pressure (CPAP) treatment is associated with substantial health care costs, morbidity and mortality, and has been a leading obstacle in the effective management of obstructive sleep apnea (OSA). Successful interventions to improve CPAP adherence may ultimately include a variety of components. For patients living with spouses (refers to all domestic partners), the spouse will likely be an integral component to any successful intervention. Developing understanding of the role of spouses in adherence to CPAP has been identified to be a critical research need. This review expands the investigation of CPAP adherence to a broader context, from an exclusive focus on individual patients to a dyadic perspective encompassing both patients and their spouses. A conceptual framework based on social support and social control theories is proposed to understand spousal involvement in CPAP adherence. Methodologies for future investigations are discussed, along with implications for developing interventions that engage both patients and their spouses to improve CPAP use

Gender differences in baseline functional status and response to continuous positive airway pressure in milder obstructive sleep apnea

Background. The limited understanding of obstructive sleep apnea (OSA) in women and the gender bias observed in diagnosis and research poses a critical challenge to appropriate management for women. In particular, little is known about gender differences in functional status, and the impact of continuous positive airway pressure (CPAP), the primary treatment option for OSA, on this significant outcome. This study specifically examined gender differences in functional status, daytime sleepiness, and mood states prior to treatment, and in response to CPAP in milder OSA, which represents the largest segment of the OSA population and the most common degree of disease severity in female patients. Methods and results. A secondary analysis of data from a multicenter international clinical trial of CPAP treatment efficacy in 138 males and 98 females was conducted. Women had significantly lower activity and poorer intimacy and sexual relationships measured by the Functional Outcomes of Sleep Questionnaire, and poorer physical health measured by the SF-36 compared to men, after adjusting for age, body mass index (BMI), apnea hypopnea index (AHI), and psychiatric comorbidity. No gender differences were observed in the Epworth Sleepiness Scale scores, but longer reaction times measured by the Psychomotor Vigilance Task indicating more objective daytime sleepiness were observed in women. After adjusting for age, BMI, and AHI, women reported more fatigue with a lower vigor-activity level measured by the Profile of Mood States. When further adjusting for psychiatric comorbidity, men reported significantly greater depressed mood than women. Mood disturbances particularly fatigue, daytime sleepiness, and gender were predictive of decreased baseline functional status. Following eight weeks of CPAP treatment, significant improvements in functional status, daytime sleepiness, and mood disturbances were generally observed within each gender. The magnitude of change was greater for men than women in the improvements in anxiety and confusion, otherwise there was no difference between the groups. Conclusions. These results demonstrate the existence of gender differences in functional status and some symptoms in patients with OSA. Further investigation of gender differences and response to treatments are necessary to facilitate the development of interventions to promote functional status tailored to patient gender

Gender differences in baseline functional status and response to continuous positive airway pressure in milder obstructive sleep apnea

Background. The limited understanding of obstructive sleep apnea (OSA) in women and the gender bias observed in diagnosis and research poses a critical challenge to appropriate management for women. In particular, little is known about gender differences in functional status, and the impact of continuous positive airway pressure (CPAP), the primary treatment option for OSA, on this significant outcome. This study specifically examined gender differences in functional status, daytime sleepiness, and mood states prior to treatment, and in response to CPAP in milder OSA, which represents the largest segment of the OSA population and the most common degree of disease severity in female patients. Methods and results. A secondary analysis of data from a multicenter international clinical trial of CPAP treatment efficacy in 138 males and 98 females was conducted. Women had significantly lower activity and poorer intimacy and sexual relationships measured by the Functional Outcomes of Sleep Questionnaire, and poorer physical health measured by the SF-36 compared to men, after adjusting for age, body mass index (BMI), apnea hypopnea index (AHI), and psychiatric comorbidity. No gender differences were observed in the Epworth Sleepiness Scale scores, but longer reaction times measured by the Psychomotor Vigilance Task indicating more objective daytime sleepiness were observed in women. After adjusting for age, BMI, and AHI, women reported more fatigue with a lower vigor-activity level measured by the Profile of Mood States. When further adjusting for psychiatric comorbidity, men reported significantly greater depressed mood than women. Mood disturbances particularly fatigue, daytime sleepiness, and gender were predictive of decreased baseline functional status. Following eight weeks of CPAP treatment, significant improvements in functional status, daytime sleepiness, and mood disturbances were generally observed within each gender. The magnitude of change was greater for men than women in the improvements in anxiety and confusion, otherwise there was no difference between the groups. Conclusions. These results demonstrate the existence of gender differences in functional status and some symptoms in patients with OSA. Further investigation of gender differences and response to treatments are necessary to facilitate the development of interventions to promote functional status tailored to patient gender

Individualized sleep promotion in acute care hospitals: Identifying factors that affect patient sleep

Background/aimOne major challenge of inpatient sleep promotion is that there is no "one-size-fits-all" intervention as patients' sleep may be bothered by different factors. A tool evaluating factors that disturb patient sleep is greatly needed as a foundation for generating a personalized action plan to address the patient's specific need for sleep. Unfortunately such tools are currently unavailable in clinical practice. In this study we developed and psychometrically evaluated a brief assessment tool for sleep disruptors important for hospitalized patients, the Factors Affecting Inpatient Sleep (FAIS) scale.MethodsThe FAIS items were developed by literature review and validated by content validity testing. A survey collected from 105 hospitalized patients was used to select the most significant sleep disruptors. Psychometric evaluation using survey data included item analysis, principal components analysis, and internal consistency reliability.ResultsThe final FAIS scale included 14 items in three subscales explaining 56.4% of the total variance: 1) emotional or physical impairment due to illness or hospitalization; 2) sleep disturbance due to discomfort or care plan schedule; 3) sleep interruption due to hospital environment or medical care. The Cronbach's alpha coefficient for the FAIS scale was 0.87, and the reliability of the subscales ranged from 0.72 to 0.81.ConclusionThe FAIS is a brief tool assessing sleep disruptors important for patients, and is empirically grounded, judged to have content validity, and has demonstrated psychometric adequacy. The FAIS scale can be used to guide the development of an individualized patient-centered sleep promotion plan