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

The German Society of Pneumology initiated 2021 the AWMF S1 guideline Long COVID/Post-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendations describe current Long COVID/Post-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 explicit practical claim and will be developed and adapted by the author team based on the current increase in knowledge.

Adult skin acute stress responses to short-term environmental and internal aggression from exposome factors.

Exposome factors that lead to stressed skin can be defined as any disturbance to homeostasis from environmental (meteorological factors, solar radiation, pollution or tobacco smoke) and/or internal exposure (unhealthy diet, hormonal variations, lack of sleep, psychosocial stress). The clinical and biological impact of chronic exposome effects on skin functions has been extensively reviewed, whereas there is a paucity of information on the impact of short-term acute exposure. Acute stress, which would typically last minutes to hours (and generally no more than a week), provokes a transient but robust neuroendocrine-immune and tissue remodelling response in the skin and can alter the skin barrier. Firstly, we provide an overview of the biological effects of various acute stressors on six key skin functions, namely the skin physical barrier, pigmentation, defences (antioxidant, immune cell-mediated, microbial and microbiome maintenance), structure (extracellular matrix and appendages), neuroendocrine and thermoregulation functions. Secondly, we describe the biological and clinical effects on adult skin from individual exposome factors that elicit an acute stress response and their consequences in skin health maintenance. Clinical manifestations of acutely stressed skin may include dry skin that might accentuate fine lines, oily skin, sensitive skin, pruritus, erythema, pale skin, sweating, oedema and flares of inflammatory skin conditions such as acne, rosacea, atopic dermatitis, pigmentation disorders and skin superinfection such as viral reactivation. Acute stresses can also induce scalp sensitivity, telogen effluvium and worsen alopecia.

Assessment of Brain Derived Neurotrophic Factor in hair to study stress responses: A pilot investigation.

To study pathogenic stress-effects in health and disease, it is paramount to define easy access parameters for non-invasive analysis of biological change in response to stress. Hair samples successfully provide this access for the study of hypothalamus-pituitary-adrenal axis (HPA) changes. In this study, we assess the hair expression and corresponding epigenetic changes of a neurotrophin essential for autonomic nervous system function and mental health: brain derived neurotrophic factor (BDNF). In three independent studies in healthy academic volunteers (study I: German students, N=36; study II, German academic population sample, N=28; study III: Mexican students, N=115), BDNF protein expression or BDNF gene (BDNF) histone acetylation was determined. Simultaneously, mental distress and distress-associated somatic complaints were assessed by self-report. In study I, we found a negative correlation between hair-BDNF protein level and hair-cortisol as well as between hair-BDNF and somatic complaints, while hair-cortisol correlated positively with mental distress. In study II, we found a negative correlation between H4 histone acetylation at the BDNF gene P4-promoter and somatic complaints. Regression analysis confirmed confounder stability of associations in both studies. In study III, we confirmed study I and found lower hair-BDNF protein level in volunteers with high somatic complaints, who also reported higher mental distress during the end of term exams. The results indicate that BDNF protein levels can be detected in clipped hair and are associated with somatic complaints and stress in life. In addition, we concluded that plucked hair can provide material for the study of epigenetic changes in stress-affected tissues. These tools can prove valuable for future studies on distress, both under experimental and field conditions.

[Stress and the molecular basis of psychosomatics]. / Stress und molekulare Psychosomatik.

Stress and skin-an inseparable pair, this is how many of our patients perceive it and even clinicians are willing to integrate psychosomatic aspects into their recommendations if nothing from the somatic repertoire provides sufficient treatment. How the stress reaches the skin however is still an enigmatic matter to most lay people and professionals alike. Interestingly, psychoneuroimmunological research since the 1970s has produced a flood of valuable data. We now know that stressors, be it biochemical or psychoemotional, always elicit a neuroendocrine stress reaction with consequences for the immune response and therefore especially chronic inflammatory skin diseases. Here we employ allergic inflammation/atopic dermatitis and psoriasis as instructive model diseases to discuss basic mechanisms of molecular psychosomatic effects on chronic inflammation. The aim is to enhance pathogenetic understanding and open the door for the development and employment of integrated therapeutic concepts in dermatology.

Psychological support of skin cancer patients.

The diagnosis of skin cancer imposes a great stress on our patients. Ultraviolet (UV) radiation-induced skin cancers are on the rise and frequently occur in younger patients and unexposed sites despite improved protective behaviour. Environmental factors and lifestyle habits have changed greatly in the last century and in addition to UV radiation exposure, psychosocial stressors and physical inactivity may play a role in the rising tumour incidence. With environmental stressors such as UV radiation they share the capacity to change the stress reaction. So far research into the interaction between stress, cancer and psychosocial intervention has generated some interesting results with respect to improvement of quality of life and the function of the hypothalamic-pituitary-adrenal axis, the sympathetic axis and natural killer cells. These results hint at a suppressive effect of chronic stress on cellular immunity and the importance of a sufficient length and intensity of any psychosocial intervention for it to be effective. Nevertheless, the evidence remains inconclusive and does not take into account the findings of current psychoneuroimmunological research. This research has demonstrated the importance of a third stress axis along which neurotrophins and neuropeptides are effective. Along this axis, regulatory mechanisms may contribute to suppress tumoricidal immune responses. This may be instrumental in the establishment of an immune response that promotes tumour progression and holds important implications for integrated therapeutic strategies. However, research into the psychoneuroimmunological benefits of psychosocial intervention is largely missing, and future interdisciplinary research is warranted for understanding and further promoting improved quality of life and psychological as well as physical well-being after psychosocial intervention.

Neurotrophins act as neuroendocrine regulators of skin homeostasis in health and disease.

Neurotrophins regulate cutaneous innervation, act as growth and motility factors on structural skin cells such as keratinocytes and fibroblasts, modulate cutaneous immune function and even serve as stress mediators in skin biology. The multilayered neurotrophin interaction with skin biology through high affinity specific tyrosinekinase receptors and the Janus-faced p75 receptor, which depending on ligand and co-receptor expression can serve as a low-affinity pan-neurotrophin receptor or a high affinity proneurotrophin receptor, guaranties this neuroendocrine peptide family a central position in the control of skin homeostasis in health and disease. It is a challenging task for future research efforts to integrate our knowledge on differential neurotrophin expression patterns and signaling pathways into complex concepts of neuroendocrine tissue remodeling and pathogenetic processes. In addition, we need to improve our understanding of the role of neurotrophin processing enzymes, associated co-receptors and intracellular adaptor molecules in specific cutaneous cell populations to design precise interaction tools for research and treatment. Such tools will allow us to utilize this ancient growth factor family in the management of neurotrophin responsive pathogenetic pathways and cutaneous diseases such as neurogenic inflammation, peripheral nerve degeneration, wound healing, atopic dermatitis or psoriasis.

Neuronal plasticity and neuroregeneration in the skin -- the role of inflammation.

The skin develops probably the densest and most complex innervation of all mammalian organs, consisting of sensory and autonomic nerves loaded with a plethora of neuropeptides and neurotransmitters. Skin innervation, as well as the expression patterns of neurotrophins and their receptors, is subject to dramatic changes during not only morphogenesis but also adult tissue remodeling under physiological or inflammatory conditions. Bilateral neuroimmune interactions are the basis of adaptive responses to tissue remodeling (such as hair cycling), psycho-emotional stress or skin inflammation. Dermatitis and hair loss may be exacerbated by stress-induced neurogenic inflammation. In addition, selected inflammatory skin diseases are associated with increased innervation. Finally, inflammatory cytokines influence the cutaneous expression of neurotrophins, as well as neurotrophin-induced neurite outgrowth following axotomy. Here, we review key studies on bilateral neuroimmune interactions in the skin under both healthy and disease conditions to provide a basis for future research on the role of inflammation in peripheral nerve regeneration.