Background: A needs assessment for patients with hidradenitis suppurativa (HS) will support advancements in multidisciplinary care, treatment, research, advocacy, and philanthropy.

Background Atopic dermatitis (AD) is the most common inflammatory skin disease, but treatment options for moderate-to-severe disease are limited. Ustekinumab is an IL-12/IL-23p40 antagonist that suppresses Th1, Th17 and Th22 activation, commonly used for psoriasis patients. Objective We sought to assess efficacy and safety of ustekinumab in moderate-to-severe AD patients. Methods In this phase II, double-blind, placebo-controlled study, 33 patients with moderate-to-severe AD were randomly assigned to either ustekinumab (n=16) or placebo (n=17), with subsequent crossover at 16wks, and last dose at 32wks. Background therapy with mild topical steroids was allowed to promote retention. Study endpoints included clinical (SCORAD50) and biopsy-based measures of tissue structure and inflammation, using protein and gene expression studies. Results The ustekinumab group achieved higher SCORAD50 responses at 12wks, 16wks (the primary endpoint), and 20wks compared to placebo, but the difference between groups was not significant. The AD molecular profile/transcriptome showed early robust gene modulation, with sustained further improvements until 32wks in the initial ustekinumab-group. Distinct and more robust modulation of Th1, Th17 and Th22 but also Th2-related AD genes was seen after 4wks of ustekinumab treatment (i.e. MMP12, IL-22, IL-13, IFN-γ, elafin/PI3, CXCL1, CCL17; p<0.05). Epidermal responses (K16, terminal differentiation) showed faster (4wks) and long-term regulation (32wks) from baseline in the ustekinumab-group. No severe adverse events were observed. Conclusions Ustekinumab had clear clinical and molecular effects, but clinical outcomes might have been obscured by a profound “placebo” effect, most likely due to background topical glucocorticosteroids and possibly insufficient dosing for AD.

TO localize basic protein (BP) in the lamellar structure of central and peripheral myelin, we perfused newborn and 7-11-day rat pups with a phosphate-buffered fixative that contained 4% paraformaldehyde and 0.05 or 0.2% glutaraldehyde. Teased, longitudinally split or "brush" preparations of optic and trigeminal nerves were made by gently teasing apart groups of myelinated fibers with fine forceps or needles. Some of these preparations were immunostained without pretreatment in phosphate-buffered antiserum to BP according to the peroxidase-antiperoxidase method. Others were pretreated in ethanol before immunostaining. Then, all of them were dehydrated, embedded in Epon, and sectioned for electron microscopic study. In optic and trigeminal nerves that were not pretreated, myelin, glial cells, and their organelles were well preserved. BP immunostaining was present on cytoplasmic faces of oligodendroglial and Schwann cell membranes that formed mesaxons and loose myelin spirals. In compact central and peripheral myelin, reaction product was located in major dense line regions, and the myelin periodicity was the same as that observed in unstaiffed control myelin that had been treated with preimmune serum. In ethanol-pretreated tissue, the myelin periodicity was reduced but dense line staining still was present. Our immunocytochemical demonstration of dense line localization of BP in both CNS and PNS myelin that was not disrupted or pretreated with solvents is important because of conflicting evidence in earlier immunostaining studies. Our results also support biochemical and histochemical evidence suggesting that BP exists in vivo as a membrane protein interacting with lipids on the cytoplasmic side of the bilayer in the spirally wrapped compact myelin membrane.Basic protein (BP) is a major constituent of central nervous system (CNS) myelin (3,9,23,40). It has a molecular weight of about 18,500, is antigenic, and is thought to have an important role in the formation and maintenance ofmyelin's compact lameUar structure (5,9,23, 48). Myelin isolated from the peripheral nervous system (PNS) contains smaller amounts of a basic protein cared Pl (7,8,15). Since Pl and BP have almost the same molecular weight (7,8,15) and amino acid sequence (7), they probably are identical or very closely related proteins (4,7,8,15,49).The localization of BP in the lamellar structure of myelin is an important issue for those interested in membrane assembly and maintenance. Investigators have used immunocytochemical methods and specific antisera to study this directly and both dense line (16, 39) and intraperiod region (27, 43) localizations have been described. But in all of these experiments, immunostaining was only observed in myelin pretreated with solvents like ethanol (27), in myelin lametlae broken by tissue processing procedures (16, 39), or in myelin disrupted by isolation for biochemical study (43).Since different localizations were obtained and the methods 2 used in the above studies broke up membranes or could have extra...

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