Prevalence of anxiety, depression and post-traumatic stress disorder among the caregivers of children and adolescents diagnosed with cancer in Oman: a multicentre, prospective cohort study

Objectives
To assess the prevalence of anxiety, depression and post-traumatic stress disorder (PTSD) and their associated factors among the caregivers of children diagnosed with cancer in Oman and explore the changes in psychological outcomes over time.

Design
A multicentre, prospective, cohort study.

Setting
The National Oncology Centre of the Royal Hospital, the Sultan Qaboos University Hospital and the Sultan Qaboos Comprehensive Cancer Care and Research Centre in Muscat, Oman.

Participants
Caregivers of Omani children and adolescents diagnosed with cancer at the three primary cancer referral centres in Oman.

Outcome measures
Validated Arabic versions of the State-Trait Anxiety Inventory, the Centre for Epidemiologic Studies Depression Scale and the Impact of Event Scale-Revised were used to screen for symptoms of anxiety, depression and PTSD, respectively. The first assessment (T1) was conducted any time within the first 3 months of the child’s diagnosis, while the second assessment (T2) was conducted 3–6 months after T1. Multivariate linear regression models were used to investigate the association between socio-demographic and clinical characteristics and average anxiety, depression and PTSD scores.

Results
Of the 92 caregivers of Omani children and adolescents diagnosed with cancer, 45.7%, 53.3%, 45.7% and 68.5% exhibited state anxiety, trait anxiety, depression and PTSD at T1. Subsequently, prevalence rates of these conditions decreased to 32.6%, 42.4%, 33.7% and 55.4%, respectively, at T2. Between T1 and T2, the prevalence of state anxiety decreased significantly, as did average state anxiety and PTSD scores (p

Leggi
Aprile 2025

Smartphone-based ecological momentary music intervention to reduce stress in Turkish immigrant women: protocol

Background
Immigrant women frequently encounter ethnic discrimination (ED) and/or stressful events in their daily lives. To mitigate the risk of resulting health impairments, we developed an ecological momentary music intervention (EMMI-T) to reduce psychological and biological stress levels in the daily lives of Turkish immigrant women. The feasibility of the EMMI-T was confirmed in a pilot study (n=20). Here, we present the protocol of our proposed study to investigate the effectiveness of the EMMI-T.

Methods
Fifty Turkish immigrant women perceiving chronic ED will take part in the 35-day study. During all three study periods (ie, baseline, intervention and post-intervention), participants will use a smartphone-based app to provide discrimination-related and stress-related data four times a day. Additionally, they will report every discriminatory and/or stressful event. During the intervention period, subsequently after such event-based data entries, participants will be allocated to either an intervention event (music listening for 10 or 20 min) or a control event (no music listening). Irrespective of event type, the app will signal 20 min after the initial event-based data entry for additional data collection. Every data entry will be accompanied by the collection of a saliva sample for analysis of biological stress markers (alpha-amylase, cortisol).

Analysis
This intraindividual randomised design will allow us to test immediate (ie, before vs after music listening) and intermediate (ie, baseline period vs postintervention period) effects of the EMMI-T on psychological and biological stress levels. To test our hypotheses, we will use multilevel modelling.

Ethics and dissemination
Positive ethical approval was given by the institutional review board of the University of Vienna (reference number 00575). The results of our study will be disseminated at conferences and submitted to a peer-reviewed journal.

Trial registration number
NCT05829031.

Leggi
Aprile 2025

The effect of home-based behavioural weight loss combined with pelvic floor muscle training in women seeking weight loss combined with stress urinary incontinence: protocol for a randomised controlled trial

Introduction
Recent guidelines suggest behavioural weight loss (BWL) and pelvic floor muscle training (PFMT) as first-line treatment approaches for women with both obesity and stress urinary incontinence (SUI). However, the optimal therapeutic and management strategies for these populations remain uncertain.

Methods and analysis
This assessor-blinded parallel-group randomised controlled trial aims to compare the efficacy of BWL alone, BWL plus conventional PFMT and BWL plus PFMT with a biofeedback device for women who are overweight or obese experiencing SUI or SUI-predominant mixed urinary incontinence. A total of 120 eligible women will be randomly assigned at a 1:1:1 ratio. All the three groups will be subjected to a 3-month self-supervision intervention after randomisation and will be assessed at baseline, after the 3-month intervention, 6 months after the intervention and 12 months after the intervention. The primary outcome measure is the self-reported severity of urinary incontinence assessed by the International Consultation on Incontinence Questionnaire-Urinary Incontinence short form. The secondary outcomes include weight loss effectiveness, pelvic muscle strength, pelvic floor ultrasound, three-dimensional body posture, adherence to the intervention and questionnaires for symptoms of pelvic organ prolapse, quality of life and sexual function.

Ethics and dissemination
This study has been approved by the Peking Union Medical College Hospital ethics committee (K5504). All results from the study will be submitted to international journals and international conferences.

Trial registration number
This trial has been registered with the Chinese Clinical Trial Registry (ChiCTR2400084015).

Leggi
Marzo 2025

The effect of home-based behavioural weight loss combined with pelvic floor muscle training in women seeking weight loss combined with stress urinary incontinence: protocol for a randomised controlled trial

Introduction
Recent guidelines suggest behavioural weight loss (BWL) and pelvic floor muscle training (PFMT) as first-line treatment approaches for women with both obesity and stress urinary incontinence (SUI). However, the optimal therapeutic and management strategies for these populations remain uncertain.

Methods and analysis
This assessor-blinded parallel-group randomised controlled trial aims to compare the efficacy of BWL alone, BWL plus conventional PFMT and BWL plus PFMT with a biofeedback device for women who are overweight or obese experiencing SUI or SUI-predominant mixed urinary incontinence. A total of 120 eligible women will be randomly assigned at a 1:1:1 ratio. All the three groups will be subjected to a 3-month self-supervision intervention after randomisation and will be assessed at baseline, after the 3-month intervention, 6 months after the intervention and 12 months after the intervention. The primary outcome measure is the self-reported severity of urinary incontinence assessed by the International Consultation on Incontinence Questionnaire-Urinary Incontinence short form. The secondary outcomes include weight loss effectiveness, pelvic muscle strength, pelvic floor ultrasound, three-dimensional body posture, adherence to the intervention and questionnaires for symptoms of pelvic organ prolapse, quality of life and sexual function.

Ethics and dissemination
This study has been approved by the Peking Union Medical College Hospital ethics committee (K5504). All results from the study will be submitted to international journals and international conferences.

Trial registration number
This trial has been registered with the Chinese Clinical Trial Registry (ChiCTR2400084015).

Leggi
Marzo 2025

An NRF2/β3-Adrenoreceptor Axis Drives a Sustained Antioxidant and Metabolic Rewiring Through the Pentose-Phosphate Pathway to Alleviate Cardiac Stress

Circulation, Ahead of Print. BACKGROUND:Cardiac β3-adrenergic receptors (ARs) are upregulated in diseased hearts and mediate antithetic effects to those of β1AR and β2AR. β3AR agonists were recently shown to protect against myocardial remodeling in preclinical studies and to improve systolic function in patients with severe heart failure. However, the underlying mechanisms remain elusive.METHODS:To dissect functional, transcriptional, and metabolic effects, hearts and isolated ventricular myocytes from mice harboring a moderate, cardiac-specific expression of a humanADRB3transgene (β3AR-Tg) and subjected to transverse aortic constriction were assessed with echocardiography, RNA sequencing, positron emission tomography scan, metabolomics, and metabolic flux analysis. Subsequently, signaling and metabolic pathways were further investigated in vivo in β3AR-Tg and ex vivo in neonatal rat ventricular myocytes adenovirally infected to express β3AR and subjected to neurohormonal stress. These results were complemented with an analysis of single-nucleus RNA-sequencing data from human cardiac myocytes from patients with heart failure.RESULTS:Compared with wild-type littermates, β3AR-Tg mice were protected from hypertrophy after transaortic constriction, and systolic function was preserved. β3AR-expressing hearts displayed enhanced myocardial glucose uptake under stress in the absence of increased lactate levels. Instead, metabolomic and metabolic flux analyses in stressed hearts revealed an increase in intermediates of the pentose-phosphate pathway in β3AR-Tg, an alternative route of glucose utilization, paralleled with increased transcript levels of NADPH-producing and rate-limiting enzymes of the pentose-phosphate pathway, without fueling the hexosamine metabolism. The ensuing increased content of NADPH and of reduced glutathione decreased myocyte oxidant stress, whereas downstream oxidative metabolism assessed by oxygen consumption was preserved with higher glucose oxidation in β3AR-Tg mice after transaortic constriction compared with wild type, together with increased mitochondrial biogenesis. Unbiased transcriptomics and pathway analysis identified NRF2 (NFE2L2) as an upstream transcription factor that was functionally verified in vivo and in β3AR-expressing cardiac myocytes, where its translocation and nuclear activity were dependent on β3AR activation of nitric oxide synthase and nitric oxide production through S-nitrosation of the NRF2-negative regulator Keap1.CONCLUSIONS:Moderate expression of cardiac β3AR, at levels observed in human cardiac myocardium, exerts metabolic and antioxidant effects through activation of the pentose-phosphate pathway and NRF2 pathway through S-nitrosation of Keap1, thereby preserving myocardial oxidative metabolism, function, and integrity under pathophysiological stress.

Leggi
Marzo 2025

An NRF2/β3-Adrenoreceptor Axis Drives a Sustained Antioxidant and Metabolic Rewiring Through the Pentose-Phosphate Pathway to Alleviate Cardiac Stress

Circulation, Ahead of Print. BACKGROUND:Cardiac β3-adrenergic receptors (ARs) are upregulated in diseased hearts and mediate antithetic effects to those of β1AR and β2AR. β3AR agonists were recently shown to protect against myocardial remodeling in preclinical studies and to improve systolic function in patients with severe heart failure. However, the underlying mechanisms remain elusive.METHODS:To dissect functional, transcriptional, and metabolic effects, hearts and isolated ventricular myocytes from mice harboring a moderate, cardiac-specific expression of a humanADRB3transgene (β3AR-Tg) and subjected to transverse aortic constriction were assessed with echocardiography, RNA sequencing, positron emission tomography scan, metabolomics, and metabolic flux analysis. Subsequently, signaling and metabolic pathways were further investigated in vivo in β3AR-Tg and ex vivo in neonatal rat ventricular myocytes adenovirally infected to express β3AR and subjected to neurohormonal stress. These results were complemented with an analysis of single-nucleus RNA-sequencing data from human cardiac myocytes from patients with heart failure.RESULTS:Compared with wild-type littermates, β3AR-Tg mice were protected from hypertrophy after transaortic constriction, and systolic function was preserved. β3AR-expressing hearts displayed enhanced myocardial glucose uptake under stress in the absence of increased lactate levels. Instead, metabolomic and metabolic flux analyses in stressed hearts revealed an increase in intermediates of the pentose-phosphate pathway in β3AR-Tg, an alternative route of glucose utilization, paralleled with increased transcript levels of NADPH-producing and rate-limiting enzymes of the pentose-phosphate pathway, without fueling the hexosamine metabolism. The ensuing increased content of NADPH and of reduced glutathione decreased myocyte oxidant stress, whereas downstream oxidative metabolism assessed by oxygen consumption was preserved with higher glucose oxidation in β3AR-Tg mice after transaortic constriction compared with wild type, together with increased mitochondrial biogenesis. Unbiased transcriptomics and pathway analysis identified NRF2 (NFE2L2) as an upstream transcription factor that was functionally verified in vivo and in β3AR-expressing cardiac myocytes, where its translocation and nuclear activity were dependent on β3AR activation of nitric oxide synthase and nitric oxide production through S-nitrosation of the NRF2-negative regulator Keap1.CONCLUSIONS:Moderate expression of cardiac β3AR, at levels observed in human cardiac myocardium, exerts metabolic and antioxidant effects through activation of the pentose-phosphate pathway and NRF2 pathway through S-nitrosation of Keap1, thereby preserving myocardial oxidative metabolism, function, and integrity under pathophysiological stress.

Leggi
Marzo 2025