Risultati per: Lo stress può essere causa di infarto ed ictus

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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).

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).

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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.

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.

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Introduction
Sexual minority women represent one of the highest-risk groups for hazardous drinking and comorbid mental health problems (eg, depression, anxiety). Research has identified cognitive (eg, expectations of rejection), affective (eg, emotion dysregulation) and behavioural (eg, avoidant coping) pathways through which minority stress (eg, stigma) places sexual minority women at disproportionate risk of hazardous drinking and comorbid depression/anxiety; yet no evidence-based interventions have been tested to address these pathways in this population. This article describes the design of Project EQuIP (Empowering Queer Identities in Psychotherapy), a randomised controlled trial of a transdiagnostic lesbian, gay, bisexual, transgender, queer (LGBTQ)-affirmative cognitive-behavioural therapy intervention (CBT) designed to improve minority stress coping and reduce sexual minority women’s hazardous drinking and mental health comorbidities.

Methods and analysis
This two-arm randomised controlled trial, funded by the National Institute on Alcohol Abuse and Alcoholism, has two objectives: (1) test the efficacy of 10 sessions of LGBTQ-affirmative CBT compared with 10 sessions of supportive counselling for sexual minority women in the community (anticipated n=450) who report hazardous alcohol use and meet criteria for a Diagnostic and Statistical Manual of Mental Disorders – 5 diagnosis of a depression or anxiety disorder and (2) examine psychosocial mechanisms and demographic factors as potential mediators and moderators, respectively, of the treatment-outcome relationship. This study’s primary outcome is change in the proportion of heavy drinking days. Secondary outcomes are changes in depressive and anxious symptoms.

Ethics and dissemination
The Yale University Human Subjects Committee reviewed and approved the research protocol. Results of this study will be disseminated to researchers and practitioners through peer-review publications and conference presentations, and directly to study participants.

Trial registration number
Registered on 17 August 2022 (ClinicalTrials.gov identifier: NCT05509166).

This parallel-design, double-blind, randomized clinical trial investigates if combination treatment with brexpiprazole and sertraline is efficacious, safe, and well tolerated in patients with posttraumatic stress disorder.

La pneumologa Dagmar Rinnenburger: “L’aspirazione per evitare infezione da ingestione”

‘Stato gold’ nell’ambito del programma ‘Eso-Angels Awards

We recently showed that a bacterial infection can break oral tolerance to food and lead to IgE-dependent mast cell activation and food-induced abdominal pain, which could constitute an important pathogenic mechanism in post-infectious irritable bowel syndrome (IBS). Here, we investigated whether similar immune mechanisms in response to psychological stress lead to food-evoked pain signaling, and thus potentially explain the pathophysiology in a larger group of patients with IBS.

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