Piezo1 integration of vascular architecture with physiological force

The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic¹⁻⁵. Studies of sensory neurons have suggested Piezo proteins as subunits of Ca²⁺-permeable non-selective cationic channels for detection of noxious mechanical impact⁶⁻⁸. Here we show Piezo1 (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezo1 profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. The importance of Piezo1 channels as sensors of blood flow was shown by Piezo1 dependence of shear-stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer sensitivity to shear stress on otherwise resistant cells. Downstream of this calcium influx there was protease activation and spatial reorganization of endothelial cells to the polarity of the applied force. The data suggest that Piezo1 channels function as pivotal integrators in vascular biology

Implementing precision methods in personalizing psychological therapies: barriers and possible ways forward

This is the final version. Available on open access from Elsevier via the DOI in this recordData availability: No data was used for the research described in the article.Highlights: • Personalizing psychological treatments means to customize treatment for individuals to enhance outcomes. • The application of precision methods to clinical psychology has led to data-driven psychological therapies. • Applying data-informed psychological therapies involves clinical, technical, statistical, and contextual aspects

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events

Investigating the feasibility and effectiveness of a modular treatment program for children and adolescents with depression and interpersonal problems: study protocol of a quasi-experimental pilot feasibility trial (CBASP@YoungAge)

Abstract Background Depression is a serious disorder in childhood and adolescence. Affected children and adolescents show significant impairments in various aspects of life. Studies on the effectiveness or efficacy of psychotherapy in depressed children and adolescents are qualitatively very heterogeneous and reveal small effect sizes. There is thus a need to better tailor psychotherapy approaches to these age groups to improve outcomes like parent-child relationship, symptomatology, or quality of life. To address this gap, we designed a modular, individualized treatment program for children and adolescents based on the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) including caregiver involvement. Method This quasi-experimental pilot feasibility trial is a phase 1 to phase 2 study investigating the feasibility and effectiveness of CBASP@YoungAge by including an intervention group (CBASP@YoungAge) and a treatment-as-usual control group. The treatment of depressive symptoms as well as interpersonal problems with primary caregivers are the main targets of CBASP@YoungAge. Personalization is ensured concerning the treatment course, caregivers’ involvement, and the patient’s age. The primary outcome relates to two areas: the feasibility of the CBASP@YoungAge treatment program in an outpatient context and a change in patients' depressive symptomatology from before to after treatment. We conduct a brief process evaluation after each session in the intervention group to closely monitor the treatment process and examine feasibility from the therapists' and patients' perspectives and mechanisms of symptom change. In addition, we consider interpersonal behavior between children and caregivers, parenting behavior, and monitor the global-health-index in children and parents as secondary outcomes. Pre-, post-, and follow-up data are evaluated. Discussion This is the first study of a modular-based intervention program for children and adolescents with depression and a clear focus on the interpersonal problems between the depressed young patient and her/his caregiver. It will provide important knowledge on the feasibility and effectiveness of the program and potential benefits of including caregivers in psychotherapy. Based on this study’s results, we plan a multicenter, randomized, controlled trial whose long-term aim is to improve the psychotherapeutic care of young patients with depression while preventing persistent courses of depressive disorders. Trial registration German Clinical Trials Register, DRKS (identifier DRKS00023281 ). Registered 17 November 2020–Retrospectively registered

Supplementary Material for: Overcoming Treatment Resistance in Chronic Depression: A Pilot Study on Outcome and Feasibility of the Cognitive Behavioral Analysis System of Psychotherapy as an Inpatient Treatment Program

<b><i>Background:</i></b> The Cognitive Behavioral Analysis System of Psychotherapy (CBASP), initially developed as an outpatient treatment for chronic depression (CD), has been adapted as a multidisciplinary 12-week inpatient program for CD. <b><i>Methods:</i></b> Seventy inpatients with CD and treatment resistance were included in a noncontrolled trial. The Hamilton Depression Rating Scale served as the primary outcome measure. Prospective naturalistic follow-up assessments were conducted 6 and 12 months after discharge. <b><i>Results:</i></b> Dropout rate was 7.1%; 90.4% perceived the program as helpful. Pre-post comparisons yielded strong effect sizes; 75.7% of the intention-to-treat sample responded, and 40.0% remitted. Nonremission was associated with experiencing temporary deterioration of symptoms during treatment. After 6 months 75.0% and after 12 months 48.0% of patients sustained response. <b><i>Conclusions:</i></b> The CBASP program appears as a feasible acute treatment for treatment-resistant CD inpatients with promising outcome. However, the continuation of treatment after discharge should be optimized especially for patients with subjective deterioration during treatment

Supplementary Material for: CBASP@home: Ein internetbasiertes Situationsanalysen-Training zur Stabilisierung des Therapieerfolgs nach stationärer Therapie für chronisch depressive Patienten

<b><i>Hintergrund: </i></b>Aufbauend auf einer ambulanten CBASP-Behandlung wurde ein stationäres multidisziplinäres Konzept zur Behandlung chronischer Depression entwickelt. Eine Pilotstudie zeigte positive Ergebnisse hinsichtlich der Wirkung dieses Konzepts, jedoch berichteten einige Patienten, dass die 12-wöchige Therapie zu kurz und die Zeit unmittelbar nach Entlassung schwierig sei. Daher wurde CBASP@home als ein internetbasiertes Situationsanalysen (SA)-Training zur Stabilisierung des erzielten Behandlungserfolgs konzipiert. CBASP@home ist eine 3-monatige Step-down-Onlineintervention. Die Patienten werden dabei unterstützt, die erlernten SA zu Hause fortzuführen und in den Alltag zu transferieren. An insgesamt 9 Terminen füllten die Patienten das SA-Formular über einen Sicherheitsserver aus und erhielten von ihrem stationären Psychotherapeuten zeitnah Rückmeldung. <b><i>Fallbericht: </i></b>In der vorliegenden Phase-I-Studie wurde die Akzeptanz und Durchführbarkeit von CBASP@home an 2 Einzelfällen untersucht. CBASP@home wurde von beiden Patienten sehr gut angenommen und als sinnvolle Unterstützung bewertet. Zudem konnte bei beiden Patienten eine zunehmende Leistungssteigerung in der SA-Durchführung bei gleichzeitig rückläufiger depressiver Symptomatik bis zur Remission beobachtet werden. <b><i>Schlussfolgerungen: </i></b>Die beiden Einzelfallauswertungen liefern Hinweise, dass CBASP@home Transferprozesse vom stationären Setting in den Alltag erleichtern, Behandlungserfolge beibehalten bzw. Rückfällen vorbeugen kann. Wenn sich diese positiven Erfahrungen in zukünftigen Studien bestätigen sollten, kann CBASP@home wesentlich zur Verbesserung der langfristigen Versorgung chronisch depressiver Patienten beitragen

European Psychiatric Association Guidance on psychotherapy in chronic depression across Europe

PURPOSE: Patients with chronic depression (CD) by definition respond less well to standard forms of psychotherapy and are more likely to be high utilizers of psychiatric resources. Therefore, the aim of this guidance paper is to provide a comprehensive overview of current psychotherapy for CD. The evidence of efficacy is critically reviewed and recommendations for clinical applications and research are given. METHODS: We performed a systematic literature search to identify studies on psychotherapy in CD, evaluated the retrieved documents and developed evidence tables and recommendations through a consensus process among experts and stakeholders. RESULTS: We developed 5 recommendations which may help providers to select psychotherapeutic treatment options for this patient group. The EPA considers both psychotherapy and pharmacotherapy to be effective in CD and recommends both approaches. The best effect is achieved by combined treatment with psychotherapy and pharmacotherapy, which should therefore be the treatment of choice. The EPA recommends psychotherapy with an interpersonal focus (e.g. the Cognitive Behavioural Analysis System of Psychotherapy [CBASP]) for the treatment of CD and a personalized approach based on the patient's preferences. DISCUSSION: The DSM-5 nomenclature of persistent depressive disorder (PDD), which includes CD subtypes, has been an important step towards a more differentiated treatment and understanding of these complex affective disorders. Apart from dysthymia, ICD-10 still does not provide a separate entity for a chronic course of depression. The differences between patients with acute episodic depression and those with CD need to be considered in the planning of treatment. Specific psychotherapeutic treatment options are recommended for patients with CD. CONCLUSION: Patients with chronic forms of depression should be offered tailored psychotherapeutic treatments that address their specific needs and deficits. Combination treatment with psychotherapy and pharmacotherapy is the first-line treatment recommended for CD. More research is needed to develop more effective treatments for CD, especially in the longer term, and to identify which patients benefit from which treatment algorithm