Lower extremity physical function and quality of life in patients with stroke: a longitudinal cohort study.

PURPOSE: Lower extremity physical function (LEPF) is a key component for mobility and is impacted in stroke-related disability. A reduction in LEPF can have a significant impact on an individual's Quality of Life (QoL). The aim of this study is to characterise the relationship between LEPF and QoL. METHODS: The MOBITEC-Stroke Study is a longitudinal cohort-study including patients with their first occurrence of ischaemic stroke. Using a linear mixed-effects model, the relationship between LEPF (timed up-and-go performance (TUG); predictor) and QoL (Stroke Specific Quality of Life scale (SS-QoL); outcome) at 3 and 12 months post stroke was investigated and adjusted for sex, age, Instrumental Activities of Daily Living (IADL), fear of falling (Falls Efficacy Scale-International Version, FES-I), and stroke severity (National Institute of Stroke Severity scale, NIHSS), accounting for the repeated measurements. RESULTS: Data of 51 patients (65 % males, 35% females) were analysed. The mean age was 71.1 (SD 10.4) years, median NIHSS score was 2.0. SS-QoL was 201.5 (SD 20.5) at 3 months and 204.2 (SD 17.4) at 12 months; the mean change was 2.7 (95% CI -2.4 to 7.7), p= 0.293. A positive association was found between baseline TUG performance (estimate log score -13.923; 95% CI -27.495 to -0.351; p=0.048) and change in SS-QoL score in multivariate regression analysis. CONCLUSION: Higher LEPF (i.e better TUG performance) at baseline, was associated with an improvement in QoL from 3- to 12-months post stroke. These results highlight the critical role of physical function, particularly baseline LEPF, in influencing the QoL of stroke survivors.

Stress Affects Mast Cell Proteases in Murine Skin in a Model of Atopic Dermatitis-like Allergic Inflammation.

Stress exposure worsens allergic inflammatory diseases substantially. Mast cells (MCs) play a key role in peripheral immune responses to neuroendocrine stress mediators such as nerve growth factor (NGF) and substance P (SP). Mast cell proteases (MCPs) and cholinergic factors (Chrna7, SLURP1) were recently described to modulate MC stress response. We studied MCPs and Chrna7/SLURP1 and their interplay in a mouse model for noise induced stress (NiS) and atopic dermatitis-like allergic inflammation (AlD) and in cultured MC lacking Chrna7. We found that the cholinergic stress axis interacts with neuroendocrine stress mediators and stress-mediator cleaving enzymes in AlD. SP-cleaving mMCP4+ MC were upregulated in AlD and further upregulated by stress in NiS+AlD. Anti-NGF neutralizing antibody treatment blocked the stress-induced upregulation in vivo, and mMCP4+ MCs correlated with measures of AlD disease activity. Finally, high mMCP4 production in response to SP depended on Chrna7/SLURP1 in cultured MCs. In conclusion, mMCP4 and its upstream regulation by Chrna7/SLURP1 are interesting novel targets for the treatment of allergic inflammation and its aggravation by stress.

S3 Guideline Atopic dermatitis: Part 1 - General aspects, topical and non-drug therapies, special patient groups.

This S3 guideline was created based on the European S3 guideline, with special consideration of the medical conditions in the German-speaking region and incorporating additions from the previous German-language version. The interdisciplinary guideline commission consisted of representatives from the German Dermatological Society, the Professional Association of German Dermatologists, the Austrian Society of Dermatology and Venereology, the Swiss Society of Dermatology and Venereology, the German Society for Allergology and Clinical Immunology, the German Society for Pediatric and Adolescent Medicine, the Professional Association of Pediatricians and Adolescent Medicine, the Society for Pediatric Allergology and Environmental Medicine, the German Society for Pediatric Rehabilitation and Prevention, the German Society for Psychosomatic Medicine and Medical Psychotherapy, the German Network for Health Services Research, the German Eczema Association and the German Allergy and Asthma Association. This first part of the guideline focuses on the definition and diagnostic aspects of atopic dermatitis (AD), addressing topical therapy as well as non-pharmacological treatment approaches such as UV therapy, psychoeducational therapy, dietary interventions for AD, allergen immunotherapy for AD, and complementary medicine. This part of the guideline also covers specific aspects of AD in children and adolescents, during pregnancy and lactation, and in the context of family planning. Additionally, it addresses occupational aspects of AD and highlights the perspective of the patients. The second part of the guideline, published separately, addresses the systemic therapy of AD.

S3 guideline Atopic dermatitis: Part 2 - Systemic treatment.

The present S3 guideline was created based on the European English-language S3 guideline, with special consideration given to the medical conditions in the German-speaking region, and with additions from the previous German-language version, in accordance with the criteria of the AWMF. This second part of the guideline addresses the systemic therapy of atopic dermatitis (AD). It covers topics such as the indication for systemic therapy in children, adolescents, and adult patients with AD. Furthermore, it addresses all medications approved for AD, such as the biologics dupilumab and tralokinumab, the Janus kinase inhibitors abrocitinib, baricitinib, and upadacitinib, as well as conventional immunosuppressive therapies with systemic glucocorticosteroids and ciclosporin. Additionally, it discusses systemic off-label therapies. The first part of the guideline, published separately, includes the definition and diagnostic aspects of AD, describes topical therapy, non-drug therapy approaches, and addresses aspects related to special patient groups.

The impact of perceived stress on the hair follicle: Towards solving a psychoneuroendocrine and neuroimmunological puzzle.

While popular belief harbors little doubt that perceived stress can cause hair loss and premature graying, the scientific evidence for this is arguably much thinner. Here, we investigate whether these phenomena are real, and show that the cyclic growth and pigmentation of the hair follicle (HF) provides a tractable model system for dissecting how perceived stress modulates aspects of human physiology. Local production of stress-associated neurohormones and neurotrophins coalesces with neurotransmitters and neuropeptides released from HF-associated sensory and autonomic nerve endings, forming a complex local stress-response system that regulates perifollicular neurogenic inflammation, interacts with the HF microbiome and controls mitochondrial function. This local system integrates into the central stress response systems, allowing the study of systemic stress responses affecting organ function by quantifying stress mediator content of hair. Focusing on selected mediators in this "brain-HF axis" under stress conditions, we distill general principles of HF dysfunction induced by perceived stress.

What Kind of Patients Receive Inpatient and Day-Hospital Treatment in Departments of Psychosomatic Medicine and Psychotherapy in Germany?

INTRODUCTION: Germany is one of the few countries with a medical specialty of psychosomatic medicine and psychotherapy and many treatment resources of this kind. OBJECTIVE: This observational study describes the psychosomatic treatment programs as well as a large sample of day-hospital and inpatients in great detail using structured diagnostic interviews. METHODS: Mental disorders were diagnosed according to ICD-10 and DSM-IV by means of Mini-DIPS and SCID-II. In addition to the case records, a modified version of the CSSRI was employed to collect demographic data and service use. The PHQ-D was used to assess depression, anxiety, and somatization. RESULTS: 2,094 patients from 19 departments participated in the study after giving informed consent. The sample consisted of a high proportion of "complex patients" with high comorbidity of mental and somatic diseases, severe psychopathology, and considerable social and occupational dysfunction including more than 50 days of sick leave per year in half of the sample. The most frequent diagnoses were depression, somatoform and anxiety disorders, eating disorders, personality disorders, and somato-psychic conditions. CONCLUSIONS: Inpatient and day-hospital treatment in German university departments of psychosomatic medicine and psychotherapy is an intensive multimodal treatment for complex patients with high comorbidity and social as well as occupational dysfunction.

Rbm20ΔRRM Mice, Expressing a Titin Isoform with Lower Stiffness, Are Protected from Mechanical Ventilation-Induced Diaphragm Weakness.

Diaphragm weakness frequently develops in mechanically ventilated critically ill patients and is associated with increased morbidity, including ventilator weaning failure, mortality, and health care costs. The mechanisms underlying diaphragm weakness are incompletely understood but may include the elastic properties of titin, a giant protein whose layout in the muscle's sarcomeres makes it an ideal candidate to sense ventilation-induced diaphragm unloading, resulting in downstream signaling through titin-binding proteins. In the current study, we investigated whether modulating titin stiffness affects the development of diaphragm weakness during mechanical ventilation. To this end, we ventilated genetically engineered mice with reduced titin stiffness (Rbm20ΔRRM), and robust (TtnΔIAjxn) or severely (TtnΔ112-158) increased titin stiffness for 8 h, and assessed diaphragm contractility and protein expression of titin-binding proteins. Mechanical ventilation reduced the maximum active tension of the diaphragm in WT, TtnΔIAjxn and TtnΔ112-158 mice. However, in Rbm20ΔRRM mice maximum active tension was preserved after ventilation. Analyses of titin binding proteins suggest that muscle ankyrin repeat proteins (MARPs) 1 and 2 may play a role in the adaptation of the diaphragm to mechanical ventilation, and the preservation of diaphragm contractility in Rbm20ΔRRM mice. Thus, Rbm20ΔRRM mice, expressing titin isoforms with lower stiffness, are protected from mechanical ventilation-induced diaphragm weakness, suggesting that titin elasticity may modulate the diaphragm's response to unloading during mechanical ventilation.

[Psychodermatology: Foundations for new developments in integrated care]. / Psychodermatologie: Grundlagen für den Aufbruch zu neuen Versorgungsformen.

The burden of a skin disease is easily understood by any observer due to its visibility: psychosocial issues are therefore ubiquitous in dermatology. Current evidence now shows that this relationship is two-way, as psychosocial stress can cause skin disease and its worsening. This interrelationship poses a major challenge.

Increased MAO-A Activity Promotes Progression of Pulmonary Arterial Hypertension.

Monoamine oxidases (MAOs), a class of enzymes bound to the outer mitochondrial membrane, are important sources of reactive oxygen species. Increased MAO-A activity in endothelial cells and cardiomyocytes contributes to vascular dysfunction and progression of left heart failure. We hypothesized that inhibition of MAO-A can be used to treat pulmonary arterial hypertension (PAH) and right ventricular (RV) failure. MAO-A levels in lung and RV samples from patients with PAH were compared with levels in samples from donors without PAH. Experimental PAH was induced in male Sprague-Dawley rats by using Sugen 5416 and hypoxia (SuHx), and RV failure was induced in male Wistar rats by using pulmonary trunk banding (PTB). Animals were randomized to receive either saline or the MAO-A inhibitor clorgyline at 10 mg/kg. Echocardiography and RV catheterization were performed, and heart and lung tissues were collected for further analysis. We found increased MAO-A expression in the pulmonary vasculature of patients with PAH and in experimental experimental PAH induced by SuHx. Cardiac MAO-A expression and activity was increased in SuHx- and PTB-induced RV failure. Clorgyline treatment reduced RV afterload and pulmonary vascular remodeling in SuHx rats through reduced pulmonary vascular proliferation and oxidative stress. Moreover, clorgyline improved RV stiffness and relaxation and reversed RV hypertrophy in SuHx rats. In PTB rats, clorgyline had no direct clorgyline had no direct effect on the right ventricle effect. Our study reveals the role of MAO-A in the progression of PAH. Collectively, these findings indicated that MAO-A may be involved in pulmonary vascular remodeling and consecutive RV failure.

Neurohormonal modulation in pulmonary arterial hypertension.

Pulmonary hypertension is a fatal condition of elevated pulmonary pressures, complicated by right heart failure. Pulmonary hypertension appears in various forms; one of those is pulmonary arterial hypertension (PAH) and is particularly characterised by progressive remodelling and obstruction of the smaller pulmonary vessels. Neurohormonal imbalance in PAH patients is associated with worse prognosis and survival. In this back-to-basics article on neurohormonal modulation in PAH, we provide an overview of the pharmacological and nonpharmacological strategies that have been tested pre-clinically and clinically. The benefit of neurohormonal modulation strategies in PAH patients has been limited by lack of insight into how the neurohormonal system is changed throughout the disease and difficulties in translation from animal models to human trials. We propose that longitudinal and individual assessments of neurohormonal status are required to improve the timing and specificity of neurohormonal modulation strategies. Ongoing developments in imaging techniques such as positron emission tomography may become helpful to determine neurohormonal status in PAH patients in different disease stages and optimise individual treatment responses.

[Can Stress Interact with SARS-CoV-2? A Narrative Review with a Focus on Stress-Reducing Interventions that may Improve Defence against COVID-19]. / Stress und Covid-19: Ein Narrativer Review über neuroendokrin-immune Mechanismen, die eine Abwehr von SARS-CoV-2 verbessern könnten.

OBJECTIVE: The COVID-19 pandemic is on the rise and causes many concerns and fears in the population as well as among medical care givers. This raises the question as to how psychosocial stress associated with the pandemic can be managed, and also if certain forms of stress can contribute to an increase in infections and critical illnesses. METHODS: Against the background of the current state of research on stress and the immune response, we provide a narrative review of studies addressing the question as to how stress can influence the immune defence against viral diseases. RESULTS: Excessive stress can compromise the barrier function of the airways and alter neuroendocrine control of immune function, which can create a virus-permissive immune response. DISCUSSION: Because certain forms of stress can play a role in the successful immune defence against viral respiratory disease, it is important to identify people with high psychosocial stress and to help them manage their stress. Conclusion Psychosocial measures that contribute to improved stress management may have a positive effect on the immune response against viral respiratory infections.

Update "Systemic treatment of atopic dermatitis" of the S2k-guideline on atopic dermatitis.

This guideline is an update from August 2020 the S2k-guideline "Atopic dermatitis" published in 2015. The reason for updating this chapter of the guideline were the current developments in the field of systemic therapy of atopic dermatitis. The agreed recommendations for systemic treatment in atopic dermatitis of the present guideline are based on current scientific data. Due to the approval of dupilumab for the treatment of moderate to severe atopic dermatitis, which cannot be treated sufficiently with topical drugs alone, this part of the guideline has now been adapted and newly consented. The indication for systemic therapy and the therapeutic response to topical and systemic treatment should be recorded and documented in a suitable form in clinic and practice. A standardized documentation of the indication for system therapy in atopic dermatitis can be recommended and is also part of the updated chapter of this guideline.

[S1 Guideline Post-COVID/Long-COVID]. / S1-Leitlinie Post-COVID/Long-COVID.

The German Society of Pneumology initiated the AWMFS1 guideline Post-COVID/Long-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendation describes current post-COVID/long-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an expilcit practical claim and will be continuously developed and adapted by the author team based on the current increase in knowledge.

Effects of Early Life Stress on Bone Homeostasis in Mice and Humans.

Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (µCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.

Skin and Psychosomatics - Psychodermatology today.

Modern psychodermatology relies on the bio-psycho-social disease model in psychosomatics, according to which biological, psychological and social factors (on various levels, from molecules to the biosphere) play a major role in the disease pathogenesis through complex, non-linear interactions over the entire disease course. It is nowadays experimentally proven that "emotions get into the skin". Recent research shows close anatomical, physiological and functional connections between skin and nervous system, already known to be ontogenetically related. These connections are reflected in many skin diseases where psychological and somatic etiological factors are closely intertwined. A holistic approach by the physician should do justice to this interdependence; biological, psychological and social factors should be adequately taken into account when taking anamnesis, making a diagnosis and choosing a therapy. The "visibility" of the skin organ bestows dermatology a special position among the various other clinical subjects, and renders a holistic, psychosomatic approach to the patient that is particularly important. The life course belongs also to modern psychodermatological approaches. Based on the modern psychodermatology concept, other corresponding sub-areas such as psychogastroenterology, psychocardiology etc. have emerged. After the theoretical part of this article, some selected skin diseases are discussed in more detail from the psychosomatic point of view.

Meijer and Vloedman's histochemical demonstration of mitochondrial coupling obeys Lambert-Beer's law in the myocardium.

Uncoupling of mitochondrial proton pumping and adenosine triphosphate (ATP) production lowers mitochondrial efficiency. Current methods to determine mitochondrial efficiency require substantial amounts of tissue and permeabilization or isolation procedures. A simple histochemical method has been described by Meijer and Vloedman (Histochemistry 69:217-232, 1980, https://doi.org/10.1007/BF00489769 ), but this was not quantitative. We found linear correlations between (1) absorbance and sections thickness and (2) absorbance and incubation time. Because the method obeys Lambert-Beer's law, we can estimate ATP/O2 ratios for healthy and overloaded right-sided rat myocardium. We related mitochondrial efficiency to the ratio between cardiolipin and its precursor phosphatidylglycerol. We found a non-linear relationship between mitochondrial efficiency and this ratio, indicating that lower mitochondrial efficiency as found in experimental pulmonary hypertension may be due to altered composition of the mitochondrial inner membrane. We conclude that the histochemical method of Meijer and Vloedman can be applied to quantify mitochondrial efficiency.

[Are there indications of "sensory processing sensitivity" (SPS) in atopically predisposed persons? - An examination of parents of children with atopic dermatitis in inpatient treatment]. / Gibt es Hinweise auf Eigenschaften der "sensory processing sensitivity" (SPS) bei atopisch veranlagten Persönlichkeiten? Eine Untersuchung an Eltern neurodermitis-kranker Kinder in stationärer Behandlung.

Are there indications of "sensory processing sensitivity" (SPS) in atopically predisposed persons? - An examination of parents of children with atopic dermatitis in inpatient treatment Objectives: Clinically, the parents of children with atopic dermatitis often give the impression of increased sensitivity. It was examined, whether the parents show characteristics of "sensory processing sensitivity" (SPS) such as extraordinary perception and processing, hypersensitivity to external stimuli, increased excitability and excessive demands. METHODS: 64 parents of children with atopic dermatitis were therefore examined with the Highly Sensitive Person Scale (Aron 1996) and three proven questionnaires. Parents with atopic disposition and children with atopic dermatitis (n = 44) were compared with nonatopic parents (n = 20). In addition, atopic parents of slightly ill children (n = 24) and atopic parents of severely ill children (n = 20) were compared with non-atopic parents of children with atopic dermatitis (n = 20). RESULTS: The comparison of 44 parents with atopic disposition with 20 non-atopic parents showed a significantly higher sensitivity, excitability, a stronger propensity for esoteric thinking and a reduced frustration tolerance in the parents with atopic disposition. They showed significant differences in three other characteristics: the mood was more depressed, life satisfaction was lower and stress increased. There were no significant differences between atopically predisposed parents of slightly ill children and atopically predisposed parents of seriously ill children. CONCLUSIONS: Atopically predisposed parents of children with atopic dermatitis show properties according to the construct of "sensory processing sensitivity" (SPS). The influence of these properties on children with atopic dermatitis, in particular the increased responsiveness (Aron & Aron 1997, Boterberg & Warreyn 2016), should be investigated in further studies.