[Anorexia nervosa: does the incidence increase during the coronavirus pandemic?] / Anorexia nervosa: Steigt die Inzidenz in der Coronapandemie?

Since the beginning of the coronavirus pandemic and the associated lockdown measures, the number of children treated in this children's hospital for eating disorders and in particular anorexia nervosa has significantly increased.An increased focus on the control of body weight with restrictive eating habits or otherwise induced weight loss (sport) can compensate for fears of loss of control. Thinking and behavioral patterns which are typical for anorexia can be assessed as dysfunctional coping strategies of the corona pandemic in order to regain control (in the sense of a substitute structure) but also as a means of coping better with feelings of depression and anxiety.

Health Care Workers' Sick Leave due to COVID-19 Vaccination in Context With SARS-CoV-2 Infection and Quarantine-A Multicenter Cross-Sectional Survey.

Background: Reactogenicity of coronavirus disease 2019 (COVID-19) vaccines can result in inability to work. The object of this study was to evaluate health care workers' sick leave after COVID-19 vaccination and to compare it with sick leave due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and quarantine leave. Methods: A multicenter cross-sectional survey was conducted at Regensburg University Medical Center and 10 teaching hospitals in South-East Germany from July 28 to October 15, 2021. Results: Of 2662 participants, 2309 (91.8%) were fully vaccinated without a history of SARS-CoV-2 infection. Sick leave after first/second vaccination occurred in 239 (10.4%) and 539 (23.3%) participants. In multivariable logistic regression, the adjusted odds ratio for sick leave after first/second vaccination compared with BNT162b2 was 2.26/3.72 for mRNA-1237 (95% CI, 1.28-4.01/1.99-6.96) and 27.82/0.48 for ChAdOx1-S (95% CI, 19.12-40.48/0.24-0.96). The actual median sick leave (interquartile range [IQR]) was 1 (0-2) day after any vaccination. Two hundred fifty-one participants (9.4%) reported a history of SARS-CoV-2 infection (median sick leave [IQR] 14 [10-21] days), 353 (13.3%) were quarantined at least once (median quarantine leave [IQR], 14 [10-14] days). Sick leave due to SARS-CoV-2 infection (4642 days) and quarantine leave (4710 days) accounted for 7.7 times more loss of workforce than actual sick leave after first and second vaccination (1216 days) in all fully vaccinated participants. Conclusions: Sick leave after COVID-19 vaccination is frequent and is associated with the vaccine applied. COVID-19 vaccination should reduce the much higher proportion of loss of workforce due to SARS-CoV-2 infection and quarantine.

[Anorexia nervosa: does the incidence increase during the coronavirus pandemic?] / Anorexia nervosa: Steigt die Inzidenz in der Coronapandemie?

Since the beginning of the coronavirus pandemic and the associated lockdown measures, the number of children treated in this children's hospital for eating disorders and in particular anorexia nervosa has significantly increased.An increased focus on the control of body weight with restrictive eating habits or otherwise induced weight loss (sport) can compensate for fears of loss of control. Thinking and behavioral patterns which are typical for anorexia can be assessed as dysfunctional coping strategies of the corona pandemic in order to regain control (in the sense of a substitute structure) but also as a means of coping better with feelings of depression and anxiety.

EGFR/Ras-induced CCL20 production modulates the tumour microenvironment.

BACKGROUND: The activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment. METHODS: The effects of EGFR/Ras on the expression and translation of CCL20 were analysed in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and ELISA in vitro. CCL20 production was verified by immunohistochemistry in different tumour tissues and correlated with clinical data. The effects of CCL20 on endothelial cell migration and tumour-associated vascularisation were comprehensively analysed with chemotaxis assays in vitro and in CCR6-deficient mice in vivo. RESULTS: Tumours facilitate progression by the EGFR/Ras-induced production of CCL20. Expression of the chemokine CCL20 in tumours correlates with advanced tumour stage, increased lymph node metastasis and decreased survival in patients. Microvascular endothelial cells abundantly express the specific CCL20 receptor CCR6. CCR6 signalling in endothelial cells induces angiogenesis. CCR6-deficient mice show significantly decreased tumour growth and tumour-associated vascularisation. The observed phenotype is dependent on CCR6 deficiency in stromal cells but not within the immune system. CONCLUSION: We propose that the chemokine axis CCL20-CCR6 represents a novel and promising target to interfere with the tumour microenvironment, and opens an innovative multimodal strategy for cancer therapy.

Failure to Thrive, Hyponatremia, Hyperkalemia - Differential Diagnostic Reflections of a Rare Genetic Disease.

Pseudohypoaldosteronism type I is a rare genetic disease of mineralocorticoid resistance that typically manifests in neonatal age. The patients are diagnosed with failure to thrive, dehydration, polyuria, vomiting, hyperkalemia, hyponatremia as well as potential metabolic acidosis accompanied by elevated values for serum aldosterone and renin. The disease is subdivided into a systemic and a renal type. Considering the renal type symptoms disappear in the toddler age group. The systemic type can -apart from the kidneys - affect colon, lungs, salivary and sweat glands. In that case symptoms persist until adulthood.

[Neonatal Behçet Disease]. / Neonataler Morbus Behçet.

BACKGROUND: Behçet's disease is a multi-system disease with inflammatory infestations, in particular of the small and middle arteries and veins. Histologically, the disease presents with the image of leukocytoclastic vasculitis. The etiology of Behçet disease is unknown, but genetic factors are discussed of playing a role in its pathogenesis. There is no known autoantibody, which could serve as a diagnostic tool. The disease usually affects patients in the 3. life decade and is rare in pediatrics. A very rare clinical form of Behçet's disease occurs during neonatal period. In this form life-threatening courses of the disease have been described. PATIENT/METHOD: In this report a family with a diagnosed disorder of the mother, where the second child presented with ulcerations in the mucous membrane area during the first week of life, will be discussed. In this case, the question of a transfer of autoantibodies from the mother, which triggers the disease in the child, must be raised. The clinical progress will be compared to known cases in the literature in order to derive recommendations for a therapeutic procedure. RESULTS: In our patient, ANAs were transiently detected, which correlated to the mother's. Fortunately, the course of the disease was mild, so that no further treatment was necessary. But, potential life-threatening events should be always held in consideration. Here, steroids seem to be the treatment of choice. CONCLUSION: In the wake of the increasing immigration of pregnant Morbus Behçet patients from Mediterranean and from countries with higher prevalence of Morbus Behçet-positive mothers should be considered.

Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1-induced pruritus.

In humans, pruritus (itch) is a common but poorly understood symptom in numerous skin and systemic diseases. Endothelin 1 (ET-1) evokes histamine-independent pruritus in mammals through activation of its cognate G protein-coupled receptor endothelin A receptor (ETAR). Here, we have identified neural endothelin-converting enzyme 1 (ECE-1) as a key regulator of ET-1-induced pruritus and neural signaling of itch. We show here that ETAR, ET-1, and ECE-1 are expressed and colocalize in murine dorsal root ganglia (DRG) neurons and human skin nerves. In murine DRG neurons, ET-1 induced internalization of ETAR within ECE-1-containing endosomes. ECE-1 inhibition slowed ETAR recycling yet prolonged ET-1-induced activation of ERK1/2, but not p38. In a murine itch model, ET-1-induced scratching behavior was substantially augmented by pharmacological ECE-1 inhibition and abrogated by treatment with an ERK1/2 inhibitor. Using iontophoresis, we demonstrated that ET-1 is a potent, partially histamine-independent pruritogen in humans. Immunohistochemical evaluation of skin from prurigo nodularis patients confirmed an upregulation of the ET-1/ETAR/ECE-1/ERK1/2 axis in patients with chronic itch. Together, our data identify the neural peptidase ECE-1 as a negative regulator of itch on sensory nerves by directly regulating ET-1-induced pruritus in humans and mice. Furthermore, these results implicate the ET-1/ECE-1/ERK1/2 pathway as a therapeutic target to treat pruritus in humans.

Serotonergic overstimulation in a preterm infant after sertraline intake via breastmilk.

The selective serotonin reuptake inhibitor (SSRI) sertraline is widely used as an antidepressant agent during pregnancy and lactation because of its low placental transfer and low level of excretion into breastmilk. Symptoms such as neonatal abstinence syndrome and serotonergic overstimulation have been reported after in utero exposure to SSRIs. These symptoms are self-limiting and usually peak within the first 48 hours after birth. In our case, a preterm infant was exposed to sertraline and its main metabolite desmethylsertraline in utero and via breastmilk. Beyond the first 48 hours after birth, the infant developed increasing clinical signs of serotonergic overstimulation associated with substance intake via breastmilk, until breastfeeding was discontinued on postnatal Day 9. In spite of a low calculated daily substance intake via breastmilk, the serum substance levels of the preterm infant were within the therapeutic range of adults. The serotonergic overstimulation may be explained by the limited metabolic capacity of the infant and the immaturity of the blood-brain barrier.

Distribution and expression of non-neuronal transient receptor potential (TRPV) ion channels in rosacea.

Rosacea is a frequent chronic inflammatory skin disease of unknown etiology. Because early rosacea reveals all characteristics of neurogenic inflammation, a central role of sensory nerves in its pathophysiology has been discussed. Neuroinflammatory mediators and their receptors involved in rosacea are poorly defined. Good candidates may be transient receptor potential (TRP) ion channels of vanilloid type (TRPV), which can be activated by many trigger factors of rosacea. Interestingly, TRPV2, TRPV3, and TRPV4 are expressed by both neuronal and non-neuronal cells. Here, we analyzed the expression and distribution of TRPV receptors in the various subtypes of rosacea on non-neuronal cells using immunohistochemistry, morphometry, double immunoflourescence, and quantitative real-time PCR (qRT-PCR) as compared with healthy skin and lupus erythematosus. Our results show that dermal immunolabeling of TRPV2 and TRPV3 and gene expression of TRPV1 is significantly increased in erythematotelangiectatic rosacea (ETR). Papulopustular rosacea (PPR) displayed an enhanced immunoreactivity for TRPV2, TRPV4, and also of TRPV2 gene expression. In phymatous rosacea (PhR)-affected skin, dermal immunostaining of TRPV3 and TRPV4 and gene expression of TRPV1 and TRPV3 was enhanced, whereas epidermal TRPV2 staining was decreased. Thus, dysregulation of TRPV channels also expressed by non-neuronal cells may be critically involved in the initiation and/or development of rosacea. TRP ion channels may be targets for the treatment of rosacea.

Neurovascular and neuroimmune aspects in the pathophysiology of rosacea.

Rosacea is a common skin disease with a high impact on quality of life. Characterized by erythema, edema, burning pain, immune infiltration, and facial skin fibrosis, rosacea has all the characteristics of neurogenic inflammation, a condition induced by sensory nerves via antidromically released neuromediators. To investigate the hypothesis of a central role of neural interactions in the pathophysiology, we analyzed molecular and morphological characteristics in the different subtypes of rosacea by immunohistochemistry, double immunofluorescence, morphometry, real-time PCR, and gene array analysis, and compared the findings with those for lupus erythematosus or healthy skin. Our results showed significantly dilated blood and lymphatic vessels. Signs of angiogenesis were only evident in phymatous rosacea. The number of mast cells and fibroblasts was increased in rosacea, already in subtypes in which fibrosis is not clinically apparent, indicating early activation. Sensory nerves were closely associated with blood vessels and mast cells, and were increased in erythematous rosacea. Gene array studies and qRT-PCR confirmed upregulation of genes involved in vasoregulation and neurogenic inflammation. Thus, dysregulation of mediators and receptors implicated in neurovascular and neuroimmune communication may be crucial at early stages of rosacea. Drugs that function on neurovascular and/or neuroimmune communication may be beneficial for the treatment of rosacea.

Role of protease-activated receptors in human skin fibrosis and scleroderma.

Proteases and their receptors have poorly understood roles in skin fibrosis and systemic scleroderma (SSc). We examined the role of protease-activated receptors (PAR(1) and PAR(2) ) in the pathophysiology of human SSc and skin fibrosis. Immunohistochemistry showed that PAR(1) immunoreactivity was positive in fibroblasts of SSc skin and healthy skin. PAR(2) immunoreactivity was positive in SSc skin, but negative in endothelial cells and fibroblasts of healthy skin. Double immunofluorescence using an antibody against smooth muscle actin (α-SMA) as a marker for myofibroblasts verified a certain percentage of myofibroblasts positive for PAR(1) and PAR(2) in SSc skin. In human dermal cultured fibroblasts (HDF), PAR(1) stimulation with or without bleomycin pretreatment mobilized intracellular calcium, indicating that the expressed PARs are functional and have effects on downstream signalling by calcium release. PAR(2) -induced intracellular calcium mobilization was only measurable in HDF after bleomycin pretreatment. Thus, PAR(1) - and PAR(2) -positive fibroblasts are increased in SSc, indicating a regulatory role. Intriguingly, bleomycin activated PAR(2) in HDF indicating that fibrosis-promoting factors have a direct effect on PAR(2) expression and functionality.

Pituitary adenylate cyclase activating polypeptide: an important vascular regulator in human skin in vivo.

Pituitary adenylate cyclase-activating peptide (PACAP) is an important neuropeptide and immunomodulator in various tissues. Although this peptide and its receptors (ie, VPAC1R, VPAC2R, and PAC1R) are expressed in human skin, their biological roles are unknown. Therefore, we tested whether PACAP regulates vascular responses in human skin in vivo. When injected intravenously, PACAP induced a significant, concentration-dependent vascular response (ie, flush, erythema, edema) and mediated a significant and concentration-dependent increase in intrarectal body temperature that peaked at 2.7°C. Topical application of PACAP induced marked concentration-dependent edema. Immunohistochemistry revealed a close association of PACAP-immunoreactive nerve fibers with mast cells and dermal blood vessels. VPAC1R was expressed by dermal endothelial cells, CD4+ and CD8+ T cells, mast cells, and keratinocytes, whereas VPAC2R was expressed only in keratinocytes. VPAC1R protein and mRNA were also detected in human dermal microvascular endothelial cells. The PACAP-induced change in cAMP production in these cells demonstrated VPAC1R to be functional. PACAP treatment of organ-cultured human skin strongly increased the number of CD31+ vessel cross-sections. Taken together, these results suggest that PACAP directly induces vascular responses that may be associated with neurogenic inflammation, indicating for the first time that PACAP may be a crucial vascular regulator in human skin in vivo. Antagonists to PACAP function may be beneficial for the treatment of inflammatory skin diseases with a neurogenic component.

LFA-1 contributes to signal I of T-cell activation and to the production of T(h)1 cytokines.

The beta(2) integrins are important for both transendothelial migration of leukocytes and T-cell activation during antigen presentation. In T cells, triggering of leukocyte functional antigen-1 (LFA-1) is required for full activation and T-helper (Th)1/Th2 differentiation. We used CD18-deficient (CD18(-/-)) mice to examine the role of LFA-1 in the activation of T cells. Compared with wild-type controls, CD18(-/-) T cells proliferated normally when stimulated with antibodies against CD3 and CD28, but secreted significantly less IFN-gamma and IL-2 than their wild-type counterparts. However, when T cells were stimulated with dendritic cells (DCs) that provide additional LFA-1 ligation, the proliferation of CD18(-/-) T cells was significantly reduced, whereas cytokine production remained impaired. The diminished proliferative capacity of CD18(-/-) T cells could be fully compensated for by additional triggering of the T-cell receptor, but not by additional stimulation through the costimulatory molecule, CD28. Thus, ligation of LFA-1 on T cells participates in regulation of Th1 cytokines in vivo. In addition, LFA-1 primarily exerts an effect as an enhancer of TCR signalling and does not facilitate classical costimulation.

Giant umbilical cord edema caused by retrograde micturition through an open patent urachus.

A giant umbilical cord is a rare finding in mature newborns and originates from different developmental etiologies. We report on a case of a mature female newborn presenting a 50 × 8-cm giant umbilical cord without further malformations. Antenatal sonographic findings of a diffuse giant umbilical cord, elevated creatinine levels of 1.3 mg/dL in umbilical cord edema, gross and histopathological findings of allantoic remnants, and umbilical urinary discharge lead to the diagnosis of a patent urachus with retrograde micturition into the umbilical cord. Postnatal surgical repair was required. In antenatal sonography, cystic and diffuse changes should be considered in the differential diagnosis of a giant umbilical cord. In cases of diffuse enlargement, elevated umbilical creatinine can support the diagnosis of a patent urachus with open leakage into the Wharton's jelly. Appropriate surgical management is required.