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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.
Trabecular bone score (TBS) is used for fracture prediction in adults, but its utility in children is limited by absence of appropriate reference values. We aimed to develop reference ranges for TBS by age, sex, and population ancestry for youth ages 5 to 20 years. We also investigated the association between height, body mass index (BMI), and TBS, agreement between TBS and lumbar spine areal bone mineral density (aBMD) and bone mineral apparent density (BMAD) Z-scores, tracking of TBS Z-scores over time, and precision of TBS measurements. We performed secondary analysis of spine dual-energy X-ray absorptiometry (DXA) scans from the Bone Mineral Density in Childhood Study (BMDCS), a mixed longitudinal cohort of healthy children (n = 2014) evaluated at five US centers. TBS was derived using a dedicated TBS algorithm accounting for tissue thickness rather than BMI. TBS increased only during ages corresponding to pubertal development with an earlier increase in females than males. There were no differences in TBS between African Americans and non-African Americans. We provide sex-specific TBS reference ranges and LMS values for calculation of TBS Z-scores by age and means and SD for calculation of Z-scores by pubertal stage. TBS Z-scores were positively associated with height Z-scores at some ages. TBS Z-scores explained only 27% and 17% of the variance of spine aBMD and BMAD Z-scores. Tracking of TBS Z-scores over 6 years was lower (r = 0.47) than for aBMD or BMAD Z-scores (r = 0.74 to 0.79), and precision error of TBS (2.87%) was greater than for aBMD (0.85%) and BMAD (1.22%). In sum, TBS Z-scores provide information distinct from spine aBMD and BMAD Z-scores. Our robust reference ranges for TBS in a well-characterized pediatric cohort and precision error estimates provide essential tools for clinical assessment using TBS and determination of its value in predicting bone fragility in childhood and adolescence. © 2022 American Society for Bone and Mineral Research (ASBMR).  相似文献   
3.
4.

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   
5.
6.
Aim: Older residents in Japan requiring rehabilitation often reside in health‐care facilities for the elderly (HCFE) prior to being discharged to home. The return home can be very stressful for both the elder and family caregiver. The purpose of this study was to clarify the differences in plans for home life between the residents of a HCFE who were scheduled for discharge home and their family caregivers. Method: Semistructured interviews were conducted with eight pairs of elders and caregivers. Results: Differences were seen in several areas, including dietary preferences, recognition of the elder’s independence, preconceptions or not knowing about the elder’s pleasurable activities, and the way of care. Conclusions: Differences with regard to enjoyable activities for the elderly arose from a lack of understanding of the lives of the elderly on the part of their families.  相似文献   
7.
Stephenson  Joan 《JAMA》2006,295(15):1763
  相似文献   
8.
The impact of recombinant human tumour necrosis factor-alpha (1 microgram kg-1 to 1 mg kg-1; 6.6 x 10(6) U mg protein-1) on blood flow, oxygen consumption and growth of a moderately TNF-sensitive rat tumour (DS-carcinosarcoma) was studied. Tumour growth was stimulated at low TNF doses (1 and 10 micrograms kg-1) and significantly retarded at higher TNF dose levels (0.1 and 1 mg kg-1). Growth changes were concomitant with variations in oxygen consumption, lactate release and acidification of the metabolic micromilieu. Both single and repeated application of low TNF doses (1-10 micrograms kg-1 i.v.) increased tumour perfusion whereas single administration of high TNF dose levels (0.1-1 mg kg-1 i.v.) reduced tumour blood flow. After repeated application of high TNF doses tumours shrank to such small sizes that perfusion measurements could not be performed within the observation period of two weeks. It is concluded that TNF effects on solid tumours are at least partially mediated by changes in tumour perfusion. Thus, an altered tumour sensitivity towards other treatment modalities, e.g. irradiation, chemotherapy or hyperthermia, can be expected after TNF therapy. A beneficial TNF effect would critically depend on the dose level employed and on the sequence and timing of various combination regimes.  相似文献   
9.
10.
Data on 232 members of a single pedigree, descended from two pairs of original parents, were made available to the participants of Genetic Analysis Workshop 8 (GAW8). In addition to information concerning age and sex, measurements for 10 quantitative traits and genotypes at 22 polymorphic marker loci were also provided for a subset of 193 of these family members. © 1993 Wiley-Liss, Inc.  相似文献   
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