Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the international Vitiligo Task Force-Part 2: Specific treatment recommendations.

BACKGROUND: The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking. OBJECTIVES: To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in different online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence for different topics included in the algorithms. A survey was then given to a core group of eight experts to resolve the remaining issues. Subsequently, the recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The recommendations provided summarize the latest evidence regarding the use of topical therapies (steroids, calcineurin inhibitors and Jak-inhibitors) and systemic therapies, including steroids and other systemic immunomodulating or antioxidant agents. The different modalities of phototherapies (NB-UVB, photochemotherapy, excimer devices and home phototherapy), which are often combined with other therapies, are also summarized. Interventional approaches as well as depigmentation strategies are presented for specific indications. Finally, the status of innovative and targeted therapies under development is discussed. CONCLUSIONS: This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs.

Stress eating: an online survey of eating behaviours, comfort foods, and healthy food substitutes in German adults.

BACKGROUND: In many people, stress is associated with changes in eating behaviour. Food products consumed during stress (comfort foods) are often unhealthy. It is rather unknown what comfort foods are consumed in Germany and what healthier food products are considered as alternatives to support stress-eaters in making healthier food choices. METHODS: This online survey was conducted in spring 2021 throughout Germany. Participants were digitally recruited by newsletters, homepages, social media, and mailing lists. The survey included a standardized questionnaire with items concerning e.g. sociodemography, stress, and nutrition. Comfort foods were pre-selected through literature search and food substitutes were defined and discussed by experts. Analyses examined comfort food consumption and substitute preferences dependent on sex, age, body mass index (BMI), and being a self-identified stress-eater. The statistical analysis was performed using R. RESULTS: Survey participants were mostly female (80.6%, 994/1234), had a mean age of 31.4 ± 12.8 years and a mean BMI of 23.4 ± 4.3 kg/m2. Participants stated, that the two favourite comfort foods were chocolate (consumed often/very often by 48.3%, 596/1234) and coffee (consumed often/very often by 45.9%, 566/1234). Regarding food substitutes, the most frequently named alternative food for chocolate and cookies was fresh fruits (for chocolate: 74.4%, 815/1096, for cookies: 62.6%, 565/902). Tea without added sugar (64.4%, 541/840) was the preferred substitute for coffee. Almost 50% of participants (48.1%, 594/1234) identified themselves as stress-eaters, of which 68.9% (408/592) stated to eat (very) often more than usual in subjective stress situations. CONCLUSIONS: The results from this work suggest that specific comfort foods and substitutes are preferred by the participants in stressful situations. This knowledge about food choices and substitutes should be investigated in further studies to improve eating behaviour in stressful situations. TRIAL REGISTRATION: The survey was registered in the German Register of Clinical Studies (Registration number: DRKS00023984 ).

The α7 Nicotinic Acetylcholine Receptor: A Promising Target for the Treatment of Fibrotic Skin Disorders.

Targeting neuroendocrine receptors can be considered as another interesting approach to treating fibrotic disorders. Previously, we could demonstrate that tropisetron, a classical serotonin receptor blocker, can modulate collagen synthesis and acts in vitro through the α7 nicotinic acetylcholine receptor (α7nAchR). Here, we used a pharmacologic approach with specific α7nAchR agonists to validate this hypothesis. PHA-543613, an α7nAchR-specific agonist, not only prevented but also reversed established skin fibrosis of mice injected with bleomycin. Interestingly, agonistic stimulation of α7nAchR also attenuated experimental skin fibrosis in the non-inflammation driven adenovirus coding for TGFß receptor Iact mouse model, indicating fibroblast-mediated and not only anti-inflammatory effects of such agents. The fibroblast-mediated effects were confirmed in vitro using human dermal fibroblasts, in which the α7nAchR-specific agonists strongly reduced the impact of TGFß1-mediated expression on collagen and myofibroblast marker expression. These actions were linked to modulation of the redox-sensitive transcription factor JunB and impairment of the mitochondrial respiratory system. Our results indicate that pharmacologic stimulation of the α7nAchR could be a promising target for treatment of patients with skin fibrotic diseases. Moreover, our results suggest a mechanistic axis of collagen synthesis regulation through the mitochondrial respiratory system.

Melanocortin 1 receptor-signaling deficiency results in an articular cartilage phenotype and accelerates pathogenesis of surgically induced murine osteoarthritis.

Proopiomelanocortin-derived peptides exert pleiotropic effects via binding to melanocortin receptors (MCR). MCR-subtypes have been detected in cartilage and bone and mediate an increasing number of effects in diathrodial joints. This study aims to determine the role of MC1-receptors (MC1) in joint physiology and pathogenesis of osteoarthritis (OA) using MC1-signaling deficient mice (Mc1re/e). OA was surgically induced in Mc1re/e and wild-type (WT) mice by transection of the medial meniscotibial ligament. Histomorphometry of Safranin O stained articular cartilage was performed with non-operated controls (11 weeks and 6 months) and 4/8 weeks past surgery. µCT-analysis for assessing epiphyseal bone architecture was performed as a longitudinal study at 4/8 weeks after OA-induction. Collagen II, ICAM-1 and MC1 expression was analysed by immunohistochemistry. Mc1re/e mice display less Safranin O and collagen II stained articular cartilage area compared to WT prior to OA-induction without signs of spontaneous cartilage surface erosion. This MC1-signaling deficiency related cartilage phenotype persisted in 6 month animals. At 4/8 weeks after OA-induction cartilage erosions were increased in Mc1re/e knees paralleled by weaker collagen II staining. Prior to OA-induction, Mc1re/e mice do not differ from WT with respect to bone parameters. During OA, Mc1re/e mice developed more osteophytes and had higher epiphyseal bone density and mass. Trabecular thickness was increased while concomitantly trabecular separation was decreased in Mc1re/e mice. Numbers of ICAM-positive chondrocytes were equal in non-operated 11 weeks Mc1re/e and WT whereas number of positive chondrocytes decreased during OA-progression. Unchallenged Mc1re/e mice display smaller articular cartilage covered area without OA-related surface erosions indicating that MC1-signaling is critical for proper cartilage matrix integrity and formation. When challenged with OA, Mc1re/e mice develop a more severe OA-pathology. Our data suggest that MC1-signaling protects against cartilage degradation and subchondral bone sclerosis in OA indicating a beneficial role of the POMC system in joint pathophysiology.

Tissue-specific fatty acids response to different diets in common carp (Cyprinus carpio L.).

Fish depend on dietary fatty acids (FA) to support their physiological condition and health. Exploring the FA distribution in common carp (Cyprinus carpio), one of the world's most consumed freshwater fish, is important to understand how and where FA of different sources are allocated. We investigated diet effects on the composition of polar and neutral lipid fatty acids (PLFA and NLFA, respectively) in eight different tissues (dorsal and ventral muscle, heart, kidney, intestine, eyes, liver and adipose tissue) of common carp. Two-year old carp were exposed to three diet sources (i.e., zooplankton, zooplankton plus supplementary feeds containing vegetable, VO, or fish oil, FO) with different FA composition. The PLFA and NLFA response was clearly tissue-specific after 210 days of feeding on different diets. PLFA were generally rich in omega-3 polyunsaturated FA and only marginally influenced by dietary FA, whereas the NLFA composition strongly reflected dietary FA profiles. However, the NLFA composition in carp tissues varied considerably at low NLFA mass ratios, suggesting that carp is able to regulate the NLFA composition and thus FA quality in its tissues when NLFA contents are low. Finally, this study shows that FO were 3X more retained than VO as NLFA particularly in muscle tissues, indicating that higher nutritional quality feeds are selectively allocated into tissues and thus available for human consumption.