Shank is a recently described family of postsynaptic proteins that function as part of the NMDA receptor-associated PSD-95 complex (Naisbitt et al., 1999 [this issue of Neuron]). Here, we report that Shank proteins also bind to Homer. Homer proteins form multivalent complexes that bind proline-rich motifs in group 1 metabotropic glutamate receptors and inositol trisphosphate receptors, thereby coupling these receptors in a signaling complex. A single Homer-binding site is identified in Shank, and Shank and Homer coimmunoprecipitate from brain and colocalize at postsynaptic densities. Moreover, Shank clusters mGluR5 in heterologous cells in the presence of Homer and mediates the coclustering of Homer with PSD-95/GKAP. Thus, Shank may cross-link Homer and PSD-95 complexes in the PSD and play a role in the signaling mechanisms of both mGluRs and NMDA receptors.
BACKGROUND AND PURPOSE
DWI has been increasingly used to characterize orbital masses and provides quantitative information in the form of the ADC, but studies of DWI of orbital masses have shown a range of reported sensitivities, specificities, and optimal threshold ADC values for distinguishing benign from malignant lesions. Our goal was to determine the optimal use of DWI for imaging orbital masses through aggregation of data from multiple centers.
MATERIALS AND METHODS
Source data from 3 previous studies of orbital mass DWI were aggregated, and additional published data points were gathered. Receiver operating characteristic analysis was performed to determine the sensitivity, specificity, and optimal ADC thresholds for distinguishing benign from malignant masses.
RESULTS
There was no single ADC threshold that characterized orbital masses as benign or malignant with high sensitivity and specificity. An ADC of less than 0.93 × 10−3 mm2/s was more than 90% specific for malignancy, and an ADC of less than 1.35 × 10−3 mm2/s was more than 90% sensitive for malignancy. With these 2 thresholds, 33% of this cohort could be characterized as “likely malignant,” 29% as “likely benign,” and 38% as “indeterminate.”
CONCLUSIONS
No single ADC threshold is highly sensitive and specific for characterizing orbital masses as benign or malignant. If we used 2 thresholds to divide these lesions into 3 categories, however, a majority of orbital masses can be characterized with >90% confidence.
BACKGROUND AND PURPOSE
Orbital inflammatory syndrome (OIS) has clinical features that overlap with orbital lymphoid lesions and orbital cellulitis. Prompt diagnosis is needed in all 3 conditions because the management of each one differs greatly. CT and MR imaging, though useful, do not always distinguish among these conditions. The aim of this study was to identify the role of diffusion-weighted imaging (DWI) in differentiating these 3 diagnoses.
MATERIALS AND METHODS
A retrospective analysis of orbital MR imaging was conducted. T1- and T2-weighted and postcontrast images were analyzed. Region-of-interest analysis was performed by using measurements in areas of abnormality seen on conventional MR imaging sequences and measurements of the ipsilateral thalamus for each patient. The DWI signal intensity of the lesion was expressed as a percentage of average thalamic intensity in each patient. Similarly, lesion apparent diffusion coefficients (ADCs) and lesion-thalamus ADC ratios were calculated. Statistical significance was determined by the Kruskal-Wallis test, and post hoc pairwise comparisons, by the Mann-Whitney U test for DWI-intensity ratio, ADC, and ADC ratio.
RESULTS
A significant difference was noted in DWI intensities, ADC, and ADC ratio between OIS, orbital lymphoid lesions, and orbital cellulitis (P < .05). Lymphoid lesions were significantly brighter than OIS, and OIS lesions were significantly brighter than cellulitis. Lymphoid lesions showed lower ADC than OIS and cellulitis. A trend was seen toward lower ADC in OIS than in cellulitis (P = .17).
CONCLUSIONS
DWI may help differentiate OIS from lymphoid lesions and cellulitis and may allow more rapid management.
Engineered polymer vesicles, termed as polymersomes, confer a flexibility to control their structure, properties, and functionality. Self-assembly of amphiphilic copolymers leads to vesicles consisting of a hydrophobic bilayer membrane and hydrophilic core, each of which is loaded with a wide array of small and large molecules of interests. As such, polymersomes are increasingly being studied as carriers of imaging probes and therapeutic drugs. Effective delivery of polymersomes necessitates careful design of polymersomes. Therefore, this review article discusses the design strategies of polymersomes developed for enhanced transport and efficacy of imaging probes and therapeutic drugs. In particular, the article focuses on overviewing technologies to regulate the size, structure, shape, surface activity, and stimuli- responsiveness of polymersomes and discussing the extent to which these properties and structure of polymersomes influence the efficacy of cargo molecules. Taken together with future considerations, this article will serve to improve the controllability of polymersome functions and accelerate the use of polymersomes in biomedical applications.
Purpose
In patients referred with blepharoptosis, the possibility of an underlying systemic cause for their ptosis can warrant a more detailed evaluation. The purpose of this study is to determine both the incidence and demographic characteristics associated with different types of ptosis in patients referred to the oculoplastics division at a tertiary care center.
Methods
A retrospective chart review was performed on all patients referred to the oculoplastics division between 2007 and 2010. Final etiology for each patient’s ptosis was determined based on history, standard eyelid measurements, and ancillary testing. Based on etiology, ptosis was categorized as aponeurotic, neurogenic, myogenic, traumatic, or congenital. Demographics, including median age and sex were analyzed for patients in each category of ptosis.
Results
Of the 251 patients, aponeurotic ptosis was the most common type of ptosis (60.2%), followed by traumatic (11.2%), congenital (10.4%), mechanical (8.8%), neurogenic (5.6%), and myogenic (4.0%). Of the neurogenic group, 35.7% of patients had cranial nerve 3 (CN 3) palsy, 28.6% had myasthenia gravis, 14.3% had aberrant regeneration, and 7.1% had Horner’s syndrome. Thirty percent of the myogenic group had chronic progressive external ophthalmoplegia (CPEO). The congenital group had the youngest median age (10.5 years), yet the aponeurotic group had the oldest (62 years).
Conclusions
A significant proportion of patients referred with ptosis had more serious conditions such as neurogenic or myogenic ptosis. Thus, clinicians should maintain a high degree of suspicion and thoroughly evaluate all patients with ptosis in order to properly assess for underlying systemic associations.
In this preliminary study, DWI improved diagnostic confidence in nearly all cases of orbital abscess when used in conjunction with contrast-enhanced imaging. DWI also confirmed abscess in a majority of cases without contrast-enhanced imaging, which may be of particular use when contrast material is contraindicated.
PurposeOcular surface and corneal epithelial wounds are common and potentially debilitating problems. Ideal treatments for these injuries would promote epithelial healing without inflammation, infection and scarring. In addition the best treatments would be cost-efficient, effective, non-toxic and easily applied. Histatin-1 peptides have been shown to be safe and effective enhancers of epithelial wound healing in other model systems. We sought to determine whether histatin-1 peptides could enhance human corneal epithelial wound healing in vitro.MethodsHistatin-1 peptides were applied to human corneal epithelial cells and compared over useful dose ranges in scratch assays using time-lapse microscopy. In addition, path finding analysis, cell spreading assays, toxicity and proliferation assays were performed to further characterize the effects of histatin-1 peptide on human corneal limbal epithelial (HCLE).ResultsHistatin-1 enhanced human corneal epithelial wound healing in typical wound healing models. There was minimal toxicity and no significant enhancement of proliferation of corneal epithelium in response to histatin-1 application. Corneal epithelial spreading and pathfinding appeared to be enhanced by the application of histatin-1 peptides.ConclusionsHistatin -1 peptide may enhance migration of HCLE cells and wound healing in vitro. These peptides may have benefit in corneal epithelial wounds and need to be investigated further.
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