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1.
Nat Commun ; 6: 6575, 2015 Mar 17.
Article in English | MEDLINE | ID: mdl-25779688

ABSTRACT

When pressure is applied to a localized area of the body for an extended time, the resulting loss of blood flow and subsequent reperfusion to the tissue causes cell death and a pressure ulcer develops. Preventing pressure ulcers is challenging because the combination of pressure and time that results in tissue damage varies widely between patients, and the underlying damage is often severe by the time a surface wound becomes visible. Currently, no method exists to detect early tissue damage and enable intervention. Here we demonstrate a flexible, electronic device that non-invasively maps pressure-induced tissue damage, even when such damage cannot be visually observed. Using impedance spectroscopy across flexible electrode arrays in vivo on a rat model, we find that impedance is robustly correlated with tissue health across multiple animals and wound types. Our results demonstrate the feasibility of an automated, non-invasive 'smart bandage' for early detection of pressure ulcers.


Subject(s)
Electric Impedance , Pressure Ulcer/diagnosis , Animals , Automation , Calibration , Dielectric Spectroscopy , Electrodes , Equipment Design , Male , Materials Testing , Naphthalenes/chemistry , Polyethylene/chemistry , Pressure , Rats , Rats, Sprague-Dawley , Wound Healing
2.
Am J Dermatopathol ; 37(1): 26-30, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24786580

ABSTRACT

A 91-year-old man presented with an ulcerated nodule on his left lower eyelid. The tumor showed an epithelial component composed of basaloid and clear cells and a stroma that contained many osteoclastic giant cells. Strong, diffuse expression for cytokeratin 17 and p63 was noted in the epithelial component, whereas no staining was present in the sarcomatoid stroma, suggesting that the osteoclast-rich stromal component represented an unusual benign stromal reaction to the carcinoma rather than a manifestation of carcinosarcoma. Further supporting this interpretation was the absence of mitotic figures and low Ki-67 proliferation index (of approximately 1%) in the stromal cells. We herein reported a case of unusual infiltrative basal cell carcinoma, accompanied by a clear cell carcinomatous features and concurrent benign osteoclastic stromal changes.


Subject(s)
Carcinoma, Basal Cell/pathology , Carcinosarcoma/pathology , Eyelid Neoplasms/pathology , Osteoclasts/pathology , Skin Neoplasms/pathology , Stromal Cells/pathology , Aged, 80 and over , Biomarkers, Tumor/analysis , Biopsy , Carcinoma, Basal Cell/chemistry , Carcinoma, Basal Cell/surgery , Cell Proliferation , Diagnosis, Differential , Eyelid Neoplasms/chemistry , Eyelid Neoplasms/surgery , Humans , Immunohistochemistry , Male , Mitotic Index , Osteoclasts/chemistry , Predictive Value of Tests , Skin Neoplasms/chemistry , Skin Neoplasms/surgery , Stromal Cells/chemistry
3.
Cell Rep ; 9(4): 1228-34, 2014 Nov 20.
Article in English | MEDLINE | ID: mdl-25456125

ABSTRACT

Somatic mutations in cancer are more frequent in heterochromatic and late-replicating regions of the genome. We report that regional disparities in mutation density are virtually abolished within transcriptionally silent genomic regions of cutaneous squamous cell carcinomas (cSCCs) arising in an XPC(-/-) background. XPC(-/-) cells lack global genome nucleotide excision repair (GG-NER), thus establishing differential access of DNA repair machinery within chromatin-rich regions of the genome as the primary cause for the regional disparity. Strikingly, we find that increasing levels of transcription reduce mutation prevalence on both strands of gene bodies embedded within H3K9me3-dense regions, and only to those levels observed in H3K9me3-sparse regions, also in an XPC-dependent manner. Therefore, transcription appears to reduce mutation prevalence specifically by relieving the constraints imposed by chromatin structure on DNA repair. We model this relationship among transcription, chromatin state, and DNA repair, revealing a new, personalized determinant of cancer risk.


Subject(s)
Carcinoma, Squamous Cell/genetics , DNA Repair/genetics , Genome, Human/genetics , Heterochromatin/genetics , Mutation Rate , Skin Neoplasms/genetics , Transcription, Genetic , DNA Packaging/genetics , DNA-Binding Proteins/deficiency , DNA-Binding Proteins/genetics , Gene Expression Regulation, Neoplastic , Germ Cells/metabolism , Humans , Proto-Oncogene Proteins/genetics
4.
J Cutan Pathol ; 41(4): 353-63, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24329979

ABSTRACT

BACKGROUND: SOX-10 expression can be demonstrated by immunohistochemistry in salivary gland myoepitheliomas, but its expression in cutaneous myoepitheliomas and in cutaneous mixed tumors with prominent myoepithelial cells has not been studied. METHODS: We assessed the staining pattern of SOX-10 in five cutaneous myoepitheliomas and six cutaneous mixed tumors with a prominent myoepithelial component among both the myoepithelial cells and cells lining lumens. In addition, we examined the staining of S100, microphthalmia-associated transcription factor (MiTF), keratin cocktail, HMK903, smooth muscle actin (SMA) and epithelial membrane antigen (EMA). RESULTS: SOX-10 positivity was seen in three of five (60%) cutaneous myoepitheliomas and in the myoepithelial cells of all cutaneous mixed tumors. SOX-10 expression on the cells lining the glandular structures in mixed tumors was variable. All myoepitheliomas and mixed tumors stained positively with S100 and negatively with MiTF. Pan-keratin, HMK903, SMA and EMA showed variable expression. CONCLUSIONS: SOX-10 is a relatively reliable marker for staining cutaneous myoepitheliomas. Cutaneous myoepitheliomas are notoriously difficult to diagnose, and the addition of SOX-10 to the repertoire of stains that can label this tumor is of practical utility. These results further support that cutaneous myoepitheliomas and cutaneous mixed tumors exist on a morphologic and immunophenotypic spectrum.


Subject(s)
Biomarkers, Tumor/biosynthesis , Gene Expression Regulation, Neoplastic , Mixed Tumor, Malignant , Myoepithelioma , Neoplasm Proteins/biosynthesis , SOXE Transcription Factors/biosynthesis , Skin Neoplasms , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Mixed Tumor, Malignant/metabolism , Mixed Tumor, Malignant/pathology , Myoepithelioma/metabolism , Myoepithelioma/pathology , Retrospective Studies , Salivary Gland Neoplasms/metabolism , Salivary Gland Neoplasms/pathology , Skin Neoplasms/metabolism , Skin Neoplasms/pathology
5.
Arch Pathol Lab Med ; 137(5): 637-41, 2013 May.
Article in English | MEDLINE | ID: mdl-23627454

ABSTRACT

CONTEXT: Providing basic medical care to patients in underserved communities around the world is a valuable service and should not be compromised. Limited publicly available information on the use of pathology services during short-term medical missions (STMMs) shows a dire need for the improved quality of care being provided. OBJECTIVE: To assess the need for clinical and anatomic pathology services in international medical missions by conducting an online survey. DESIGN: A survey containing 35 questions aimed to understand the current use and availability of routine laboratory tests during STMMs, identify the need for particular tests that would improve quality of care, and determine the perceived obstacles preventing the delivery of the care to underserved communities worldwide. Answers from 21 health care providers who served on 50 medical missions were assessed. RESULTS: Survey results revealed a significant discrepancy between the availability of pathology services in the United States and during STMMs. Statistical significance (P< .001) was found in areas of routine blood work, cytopathology, and histologic evaluation, among many others. More than half of the STMMs did not have access to basic metabolic panel, rapid hepatitis B test, and microbial cultures. Another 28% of health care providers indicated that having human immunodeficiency virus testing would have improved health care quality. CONCLUSIONS: Survey results show the need for improved pathology support during STMMs. The lack of precise diagnosis and disease monitoring has a negative effect on the quality of care provided during missions and the ability to enhance global health.


Subject(s)
Health Services Needs and Demand , Medical Missions , Pathology , Quality of Health Care , Health Care Surveys , Humans
6.
Neurosurgery ; 73(2): 247-55; discussion 255, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23670032

ABSTRACT

BACKGROUND: Ependymomas constitute approximately 40% of primary intraspinal tumors. Current World Health Organization (WHO) grading may not correlate with observed progression-free survival (PFS). OBJECTIVE: This retrospective study of prospectively collected data examines whether PFS is influenced by the histological grade or by the extent of resection. It also analyzes the usage and effectiveness of postoperative adjuvant radiotherapy. METHODS: We reviewed 134 consecutive patients with ependymomas of all grades. Pathology slides were re-reviewed and the histological grades were confirmed by a single neuropathologist. Postoperative residual or recurrence was evaluated with follow-up magnetic resonance imaging. RESULTS: There were 85 male and 49 female patients, ranging from 10 to 79 (median 41) years of age. Thirty patients had WHO grade I tumors, 101 had grade II tumors, and 3 had grade III tumors. Kaplan-Meier analysis of PFS demonstrated a mean duration of 6 years for grade I, 14.9 years for grade II, and 3.7 years for grade III (P < .001). In grade II ependymomas, mean PFS was 11.2 years with subtotal resection and 17.8 years with gross total resection (P < .01). PFS of patients who underwent subtotal resection was not significantly changed by adjuvant radiotherapy (P < .36). CONCLUSION: Patients with grade II ependymoma have significantly longer PFS than patients with grade I ependymoma. The extent of resection did not affect PFS in grade I ependymoma but it did in grade II. Contrary to its higher grade, WHO grade II ependymoma carries a better prognosis than WHO grade I ependymoma.


Subject(s)
Ependymoma/mortality , Ependymoma/pathology , Spinal Cord Neoplasms/mortality , Spinal Cord Neoplasms/pathology , Adolescent , Adult , Aged , Child , Disease-Free Survival , Ependymoma/therapy , Female , Humans , Kaplan-Meier Estimate , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Neurosurgical Procedures , Prognosis , Radiotherapy, Adjuvant , Retrospective Studies , Spinal Cord Neoplasms/therapy , Treatment Outcome , Young Adult
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