GENIPSO: a French prospective study assessing instantaneous prevalence,clinical features and impact on quality of life of genital psoriasis among patients consulting for psoriasis

Psoriasis is a common chronic inflammatory skin disease, affecting about 3% of the general population and approximately 2.5 million people in France, where this study took place. The genital area may be affected, however prevalence is poorly understood, meaning we do not know exactly how commonly this occurs. While it affects quality of life, genital psoriasis is under-recognized, probably due to the reluctance of patients to discuss genital involvement and sexual quality of life. The aims of this study, called the GENIPSO study, were to determine the prevalence of genital psoriasis, its clinical characteristics (its symptoms), whether it is associated with a particular type of psoriasis, and its impact on quality of life. The study included 776 adults seeing their doctor for psoriasis between November 2016 and March 2017. Among them, 336 (43.2%) had genital psoriasis. All these patients were aware that they had psoriasis on their genitals (genital lesions) but only 135 (40%) had already had a genital medical examination. Genital lesions were associated with (linked to) male gender, more severe psoriasis, first developing psoriasis when aged over 20 years, psoriasis of the skin folds, psoriasis on the scalp, nail and external auditory (ear) canal, but they were not associated with obesity or psoriatic arthritis. Itching was the main symptom. Genital psoriasis was associated with reduced quality of life and sexual health. The study found that genital psoriasis has a high prevalence in patients seeing their doctors about their psoriasis generally, it affects quality of life and should be better taken into account by dermatologists for the best possible care for patients.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Functional redundancy of type I and type II receptors in the regulation of skeletal muscle growth by myostatin and activin A

Myostatin (MSTN) is a transforming growth factor-β (TGF-β) family member that normally acts to limit muscle growth. The function of MSTN is partially redundant with that of another TGF-β family member, activin A. MSTN and activin A are capable of signaling through a complex of type II and type I receptors. Here, we investigated the roles of two type II receptors (ACVR2 and ACVR2B) and two type I receptors (ALK4 and ALK5) in the regulation of muscle mass by these ligands by genetically targeting these receptors either alone or in combination specifically in myofibers in mice. We show that targeting signaling in myofibers is sufficient to cause significant increases in muscle mass, showing that myofibers are the direct target for signaling by these ligands in the regulation of muscle growth. Moreover, we show that there is functional redundancy between the two type II receptors as well as between the two type I receptors and that all four type II/type I receptor combinations are utilized in vivo. Targeting signaling specifically in myofibers also led to reductions in overall body fat content and improved glucose metabolism in mice fed either regular chow or a high-fat diet, demonstrating that these metabolic effects are the result of enhanced muscling. We observed no effect, however, on either bone density or muscle regeneration in mice in which signaling was targeted in myofibers. The latter finding implies that MSTN likely signals to other cells, such as satellite cells, in addition to myofibers to regulate muscle homeostasis.

Myostatin (MSTN) is a secreted signaling molecule that normally acts to limit skeletal muscle growth (for review, see ref. 1). Mice lacking MSTN exhibit dramatic increases in muscle mass throughout the body, with individual muscles growing to about twice the normal size (2). MSTN appears to play two distinct roles in regulating muscle size, one to regulate the number of muscle fibers that are formed during development and a second to regulate the growth of those fibers postnatally. The sequence of MSTN has been highly conserved through evolution, with the mature MSTN peptide being identical in species as divergent as humans and turkeys (3). The function of MSTN has also been conserved, and targeted or naturally occurring mutations in MSTN have been shown to cause increased muscling in numerous species, including cattle (3–5), sheep (6), dogs (7), rabbits (8), rats (9), swine (10), goats (11), and humans (12). Numerous pharmaceutical and biotechnology companies have developed biologic agents capable of blocking MSTN activity, and these have been tested in clinical trials for a wide range of indications, including Duchenne and facioscapulohumeral muscular dystrophy, inclusion body myositis, muscle atrophy following falls and hip fracture surgery, age-related sarcopenia, Charcot–Marie–Tooth disease, and cachexia due to chronic obstructive pulmonary disease, end-stage kidney disease, and cancer.The finding that certain inhibitors of MSTN signaling can increase muscle mass even in Mstn^−/− mice revealed that the function of MSTN as a negative regulator of muscle mass is partially redundant with at least one other TGF-β family member (13, 14), and subsequent studies have identified activin A as one of these cooperating ligands (15, 16). MSTN and activin A share many key regulatory and signaling components. For example, the activities of both MSTN and activin A can be modulated extracellularly by naturally occurring inhibitory binding proteins, including follistatin (17, 18) and the follistatin-related protein, FSTL-3 or FLRG (19, 20). Moreover, MSTN and activin A also appear to share receptor components. Based on in vitro studies, MSTN is capable of binding initially to the activin type II receptors, ACVR2 and ACVR2B (also called ActRIIA and ActRIIB) (18) followed by engagement of the type I receptors, ALK4 and ALK5 (21). In previous studies, we presented genetic evidence supporting a role for both ACVR2 and ACVR2B in mediating MSTN signaling and regulating muscle mass in vivo. Specifically, we showed that mice expressing a truncated, dominant-negative form of ACVR2B in skeletal muscle (18) or carrying deletion mutations in Acvr2 and/or Acvr2b (13) have significantly increased muscle mass. One limitation of the latter study, however, was that we could not examine the consequence of complete loss of both receptors using the deletion alleles, as double homozygous mutants die early during embryogenesis (22). Moreover, the roles that the two type I receptors, ALK4 and ALK5, play in regulating MSTN and activin A signaling in muscle in vivo have not yet been documented using genetic approaches. Here, we present the results of studies in which we used floxed alleles for each of the type II and type I receptor genes in order to target these receptors alone and in combination in muscle fibers. We show that these receptors are functionally redundant and that signaling through each of these receptors contributes to the overall control of muscle mass.     

Chronische Transplantatdysfunktion

Chronic transplant dysfunction is a complex dynamic pathogenic process. Clinically, a decrease in glomerular filtration rate (GFR) becomes apparent leading to chronic renal insufficiency and dialysis or death from cardiovascular events. Chronic transplant dysfunction can develop into a chronic alIograft nephropathy (CAN) as a specific entity with dynamic progression. CAN includes a collection of immunologic and non-immunologic factors, rejection, ischemia time, donor and recipient characteristics and toxicity of calcineurin inhibitors. Despite improvements in immunosuppression, the long-range prognosis of renal allografts has not improved. Whether modern immunosuppressive concepts with reduction or avoidance of calcineurin inhibitors and a therapy based on antimetabolites, such as mycophenolate or mTOR-inhibitors could lead to a prolongation of transplant survival, remains to be seen.     

Extreme Photosensitivität seit der Kindheit

Ohne Zusammenfassung     

Multimodal—was ist das überhaupt?

In chronic pain syndromes multimodal treatment has proved its efficacy. However, multimodal treatment does not mean randomly combining different interventions in a potpourri of methods. Multimodal treatment must closely follow a well-proved conceptual framework. Those concepts may be well illustrated by therapy of back pain. The most elaborate model for understanding the transition from acute to chronic pain is fear avoidance. Based on this model chronic pain status is understood as a learned consequence, which resulted from patients’ anxious avoidance of body movements. In these cases, treatment of a physical pathology is not the main aim of therapy but rather functional restoration. Those multimodal programs meanwhile have demonstrated their effectiveness. However, good results not only depend on recognition of imperative elements in therapy but also on adhering to essential principles (avoidance of negative anticipation, adequate information with assurance techniques, no training of avoidance, recognition of elements of fear therapy).