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Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Objectives

To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.

Methods

Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.

Results

Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.

Conclusions

These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.  相似文献   
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Objective: To determine serotonin system abnormalities related to major depression or previous suicidal behavior.

Methods: [11C]WAY100635, [18F]altanserin and positron emission tomography were used to compare 5-HT1A and 5-HT2A binding in MDD patients divided into eight past suicide attempters (>4yrs prior to scanning) and eight lifetime non-attempters, and both groups were compared to eight healthy volunteers.

Results: The two receptor types differed in binding pattern across brain regions from each other, but there were no differences in binding between healthy volunteers and the two depressed groups or between depressed suicide attempters and non-attempters. No effects of depression severity or lifetime aggression were observed for either receptor.

Conclusion: Limitations of this study include small sample size and absence of high lethality suicide attempts in the depressed attempter group. No trait-like binding correlations with past suicide attempt or current depression were observed. Given the heterogeneity of nonfatal suicidal behavior, a larger sample study emphasizing higher lethality suicide attempts may find the serotonin biological phenotype seen in suicide decedents.  相似文献   

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ABSTRACT

Adolescents and young adults smoke waterpipe tobacco (WT) and cigarillos, at least in part, based on erroneous beliefs that these products are safer than cigarettes. To address this challenge, we used a systematic, three-phase process to develop a health communication campaign to discourage WT and cigarillo smoking among at-risk (tobacco users and susceptible non-users) 16- to 25-year-olds. In Phase 1, we used a national phone survey (N = 896) to determine salient message beliefs. Participants reported constituents (i.e., harmful chemicals) emitted by the products were worrisome. In Phase 2, we developed and evaluated four message executions, with varying imagery, tone, and unappealing products with the same constituents, using focus groups (N = 38). Participants rated one execution highly, resulting in our development of a campaign where each message: (1) identified a tobacco product and constituent in the smoke; (2) included an image of an unappealing product containing the constituent (e.g., pesticides, gasoline) to grab attention; and (3) used a humorous sarcastic tone. In Phase 3, we tested the campaign messages (17 intervention and six control) with a nationally representative online survey (N = 1,636). Participants rated intervention and control messages highly with few differences between them. Exposure to messages resulted in significant increases in all risk beliefs from pre to post (< 0.05). For WT, intervention messages increased beliefs about addiction more than control messages (p < 0.05). This systematic, iterative approach resulted in messages that show promise for discouraging WT and cigarillo use.  相似文献   
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Prolidase deficiency is a rare autosomal recessive disorder characterized by cutaneous ulcers, facial dysmorphism, recurrent infections, and intellectual disability. We report a unique case of a 6‐year‐old boy with prolidase deficiency and Crohn's disease who presented with lower extremity ulcers. Cutaneous ulcers due to prolidase deficiency are historically resistant to treatment, and we report success with the novel use of topical tacrolimus.  相似文献   
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Recurrent herpes labialis (RHL) is an incredibly common condition, though the medical literature evaluating pediatric aspects is limited. This paper assesses prevalence and therapeutic studies of pediatric RHL as well as disease complications. A comprehensive literature search of English‐language citations based on PubMed queries of selected terms was performed, with exclusion if methodology was not discussed, or if studies had 10 or fewer patients. RHL prevalence in pediatrics has been assessed by measures of point and periodic prevalence, though methodologic limitations may under‐ or over‐estimate the true prevalence of RHL. Studies have been conducted to evaluate therapeutic safety, tolerability, and efficacy of antivirals in the pediatric population. Pediatric RHL point prevalence ranges from 0.72% to 5.2% depending on the population study and the methodologies used. Pediatric RHL carries a significant public health burden and is often implicated in patients with eczema herpeticum, erythema multiforme, reactive infectious mucositis eruptions, and hypersensitivity reactions. There are few studies that evaluate the rates of occurrence of these sequelae associated with pediatric RHL.  相似文献   
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Partial nephrectomy is the mainstay of treatment for localized kidney cancer. A proportion of patients are upstaged post-operatively to locally advanced di  相似文献   
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