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1.

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   
2.

Introduction

In the United States there has been a large increase in participation in lacrosse for both males and females. The purpose of this study was to analyze the number of head injuries, injury rates (calculated using the reported number of participants) and types of head injuries that are seen in emergency departments in the United States.

Methods

We compared injuries between male and female lacrosse participants. This was a retrospective study using a publicly available database produced by the US Consumer Product Safety Commission and information about lacrosse participation from US Lacrosse.

Results

A linear regression was performed and showed a positive correlation between number of head injuries to males and time from 2002 to 2010 (R2?=?0.823; p?=?0.001). While the number of injuries to the head in female lacrosse participants was not significant. There was a negative correlation between the number of head injuries to males from 2010 to 2016 (R2?=?0.800; p?=?0.007), but again, there was no significance for female injury count (R2?=?0.417; p?=?0.117). Other significant differences between head injuries in males and females included the mechanism of injury and the type of injury recorded.

Conclusion

The most recent data from 2010 to 2016, suggest that both males and females have had a decrease in injury rate. However the total number of female head injuries is not significantly decreasing and as the sport continues to grow there will likely be more total head injuries and visits to the emergency department.  相似文献   
3.
This study compared the predictive value of the theory of planned behavior in university students in South Africa (N = 251) and the United States (N = 160) who completed an anonymous self-administered questionnaire. Multiple regression analyses revealed that condom use and intention were significantly predicted by positive condom attitude, subjective norm, self-efficacy, and attending university in South Africa. Significant interactions between country and predictors indicated that subjective norm predicted condom use and intention more strongly in the American sample than in the South African sample; attitude predicted intention more strongly in the American sample than in the South African sample; but self-efficacy predicted intention more strongly in the South African sample than in the American sample. The theory of planned behavior may provide a useful framework for interventions to reduce South African students' risk of HIV/and sexuality transmitted diseases. Such interventions should especially focus on building self-efficacy to use condoms.  相似文献   
4.
Temporoparietal and posterior cingulate metabolism deficits characterize patients with Alzheimer's disease (AD). A H(2)(15)O resting PET scan covariance pattern, derived by using multivariate techniques, was previously shown to discriminate 17 mild AD patients from 16 healthy controls. This AD covariance pattern revealed hypoperfusion in bilateral inferior parietal lobule and cingulate; and left middle frontal, inferior frontal, precentral, and supramarginal gyri. The AD pattern also revealed hyperperfusion in bilateral insula, lingual gyri, and cuneus; left fusiform and superior occipital gyri; and right parahippocampal gyrus and pulvinar. In an independent sample of 23 outpatients with mild cognitive impairment (MCI) followed at 6-month intervals, the AD pattern score was evaluated as a predictor of cognitive decline. In this MCI sample, an H2(15)O resting PET scan was carried out at baseline. Mean duration of follow-up was 48.8 (SD 15.5) months, during which time six of 23 MCI patients converted to AD. In generalized estimating equations (GEE) analyses, controlling for age, sex, education, and baseline neuropsychological scores, increased AD pattern score was associated with greater decline in each neuropsychological test score over time (Mini Mental State Exam, Selective Reminding Test delayed recall, Animal Naming, WAIS-R digit symbol; Ps<0.01-0.001). In summary, a resting PET covariance pattern previously reported to discriminate AD patients from control subjects was applied prospectively to an independent sample of MCI patients and found to predict cognitive decline. Independent replication in larger samples is needed before clinical application can be considered.  相似文献   
5.
The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.  相似文献   
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8.
An open label randomized trial conducted in rural Kentucky compared the efficacy and safety of cefixime (CFX), 8 mg/kg once daily, with those of penicillin V (PEN), 250 mg 3 times daily, in 110 pediatric patients with Group A beta-hemolytic streptococcal pharyngitis. Forty-eight CFX and 47 PEN patients were evaluable for efficacy. At the end of therapy bacteriologic eradication was 45 of 48 (94%) and 36 of 47 (77%) in the CFX and PEN V groups, respectively (P < 0.05). Up to 6 weeks posttherapy 10 (21%) CFX patients and 21 (45%) PEN patients had positive Group A beta-hemolytic Streptococcus cultures (P < 0.05). Concordant serotypes were identified from 4 of 7 CFX and 15 of 17 PEN patients with positive repeat cultures. All discordant serotypes (5 of 31) were identified at greater than 19 days posttherapy. Symptomatic treatment failures (concordant serotypes) occurred in 1 (2%) CFX and 8 (17%) PEN patients (P < 0.05). Drug-related adverse experiences consisted of 2 cases of mild diarrhea and loose stools in the CFX group and none in the PEN group. No clinically significant laboratory test abnormalities occurred in either group. CFX, once daily, was as safe as and significantly more effective than PEN given 3 times daily for the treatment of Group A beta-hemolytic streptococcal pharyngitis.  相似文献   
9.
Patients suffering from semantic dementia provide important constraints on theories of the structure and organisation of semantic memory. In this article we report one such patient, AM, whose progressive deterioration of semantics enables us to address the much-debated issue of whether conceptual structure is hierarchically organised. The hierarchical account predicts that brain damage should impair lower levels of the hierarchy (property information) before affecting higher level (category) information (Warrington and Shallice, Q. J. Exp. Psychol. 1975, 27, 635–657). We evaluate this prediction by repeated testing of AM in two studies—a semantic priming task and a verification task—over an 18 month period, contrasting the progressive deterioration of properties (functional and perceptual) and category relations (category co-ordinates and category labels). Properties were preserved longer than category information, arguing against a hierarchical account of semantic memory. In addition, functional properties were most robust to brain damage, supporting our claim that functional information plays a special role in semantic representations (Durrant-Peatfield et al., Proc. 19th Ann. Conf. of the Cognitive Science Society. Erlbaum, Mahwah, NJ, 1997, pp. 193–198. Tyler et al., Cognitive Neuropsychol. 1997, 14, 511–545).  相似文献   
10.
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