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Osteocalcin affects bone mineral and mechanical properties in female mice

Berezovska, O; Yildirim, G; Budell, W C; Yagerman, S; Pidhaynyy, B; Bastien, C; van der Meulen, M C H; Dowd, T L
Osteocalcin is one of the most abundant noncollagenous proteins in bone. Phenotypes of osteocalcin knock-out mice (OC-/-) may vary on different backgrounds and with sex. Previous studies using adult female (OC-/-) mice on a mixed genetic background (129/B6) showed osteocalcin inhibited bone formation leading to weaker bone in wild-type (OC+/+). Yet on a pure (B6) genetic background male mice revealed osteocalcin improved fracture resistance and OC-/- bones were more prone to fracture. Osteocalcin is decreased with age and in some diseases (diabetes) where bone weakness is observed. The effect of osteocalcin in adult female bone from mice on a pure B6 background is unknown. We investigated differences in bone mineral properties and bone strength in female adult (6 months) (OC+/+) and (OC-/-) mice on a pure C57BL/6J background using Fourier Transform Infrared Imaging (FTIRI), micro-computed tomography (uCT), biomechanical measurements, histomorphometry and serum turnover markers (P1NP, CTX). Similar to female age matched mice on the (129/C57) background we found B6 OC-/- mice had a higher bone formation rate, no change in bone resorption, more immature mineral, decreased crystallinity and increased trabecular bone as compared to OC+/+. In contrast, the OC-/- mice on a pure B6 background had a lower bone mineral density, lower mineral to matrix ratio resulting in reduced stiffness and weaker bone strength. Our results demonstrate some properties of the OC-/- phenotype are dependent on genetic background. This may suggest that reduced osteocalcin may contribute to fracture and weaker bone in some groups of elderly and adults with diseases where osteocalcin is low.
PMID: 31401301
ISSN: 1873-2763
CID: 4483572

Retrospective Multistudy Analysis of Axillary Odor Reduction After Microwave Treatment

Yagerman, Sarah; Brauer, Jeremy A; Geronemus, Roy G
PMID: 29360656
ISSN: 1524-4725
CID: 2929322

Evaluation of MITF, SOX10, MART-1, and R21 Immunostaining for the Diagnosis of Residual Melanoma In Situ on Chronically Sun-Damaged Skin

Mu, Euphemia W; Quatrano, Nicola A; Yagerman, Sarah E; Ratner, Desiree; Meehan, Shane A
BACKGROUND:Melanocytic immunostains can assist in margin evaluation of melanoma in situ (MIS) excisions; however, their accuracy and reliability relative to hematoxylin & eosin (H&E) is yet to be determined. OBJECTIVE:The objective of this study was to evaluate the sensitivity, specificity, and concordance of 4 melanocyte-specific immunostains for diagnosing MIS occurring on chronically sun-damaged skin. MATERIALS AND METHODS/METHODS:Serial permanent sections from representative areas of negative margin and residual tumor were stained using H&E, MITF, MART-1, SOX10, and R21 and examined in a blinded fashion. The study set included 100 digital microscopy images from 10 cases of MIS excisions from the face. Two board-certified dermatopathologists, 4 fellowship-trained Mohs surgeons, 2 Mohs fellows, and 2 dermatology residents independently reviewed the 100 images. RESULTS:The average melanocyte density was 11 versus 28 melanocytes per 0.5 mm for chronically sun-damaged skin versus residual MIS on H&E, respectively. Statistically significantly higher melanocyte densities were observed using MITF, MART-1, and SOX10 on negative margins. The sensitivity and interobserver concordance was highest using MITF and SOX10. The intraobserver agreement on 4 duplicate images was 85%. CONCLUSION/CONCLUSIONS:In conclusion, the nuclear immunostains (MITF and SOX10) show the most promise for improving the diagnosis of MIS in chronically sun-damaged skin.
PMID: 29419543
ISSN: 1524-4725
CID: 2948252

Digital imaging biomarkers feed machine learning for melanoma screening [Letter]

Gareau, Daniel S; Correa da Rosa, Joel; Yagerman, Sarah; Carucci, John A; Gulati, Nicholas; Hueto, Ferran; DeFazio, Jennifer L; Suarez-Farinas, Mayte; Marghoob, Ashfaq; Krueger, James G
We developed an automated approach for generating quantitative image analysis metrics (imaging biomarkers) that are then analysed with a set of 13 machine learning algorithms to generate an overall risk score that is called a Q-score. These methods were applied to a set of 120 "difficult" dermoscopy images of dysplastic nevi and melanomas that were subsequently excised/classified. This approach yielded 98% sensitivity and 36% specificity for melanoma detection, approaching sensitivity/specificity of expert lesion evaluation. Importantly, we found strong spectral dependence of many imaging biomarkers in blue or red colour channels, suggesting the need to optimize spectral evaluation of pigmented lesions.
PMID: 27783441
ISSN: 1600-0625
CID: 2589642

Cutis verticis gyrata

Yagerman, Sarah; Callahan, Shields; Terushkin, Vitaly; Meehan, Shane A; Pomeranz, Miriam Keltz; Friedman-Kien, Alvin
Cutis verticis gyrata that involves only the face isa rare presentation of this even rarer cutaneousanomaly. We present a 61-year-old man, whodeveloped primary essential progressive cutis verticisgyrata of the face.
PMID: 28329551
ISSN: 1087-2108
CID: 2494772

Gardner-Diamond syndrome

Park, Joyce H; Yagerman, Sarah; Feng, Hao; Kim, Randie H; Meehan, Shane A; Lewin, Jesse
Gardner-Diamond syndrome, which also is knownas autoerythrocyte sensitization disorder, is a raresyndrome of inflammatory, edematous papulesthat evolve into painful ecchymoses on the trunkand lower legs after a period of stress with no priorhistory of trauma. This syndrome usually occurs inwomen with a history of psychiatric disorders, themost common one being depression. Although theexact mechanism of injury is not well understood,it is hypothesized that these patients haveautoantibodies to phosphatidylserine, which is aphospholipid membrane component in erythrocytes.Treatment for this disorder includes symptomatictherapies and psychotropic medications to treat theunderlying psychiatric disorder.
PMID: 28329546
ISSN: 1087-2108
CID: 2494722

Acquired aquagenic papulotranslucent acrokeratoderma

Yagerman, Sarah E; Lager, Marie; Soter, Nicholas A
Aquagenic papulotranslucent acrokeratoderma isa rare condition with the development of white-totransluscentpapules and plaques after exposureto water. While the first report was described asan autosomal dominant hereditary condition,there have since been acquired cases reported inassociation with cystic fibrosis, with prior exposureto a drug, or as an idiopathic condition. We presenta 24-year-old man with acquired aquagenicpapulotranslucent acrokeratoderma that has beenpresent since infancy, without a family history,without prior drug exposure, and without anypersonal or family history of cystic fibrosis. Thus fartreatment with urea cream, calipotriene ointment,vitamin E cream, and clobetasol ointment hasbeen ineffective. Our patient will be treated withbotulinum toxin.
PMID: 28329534
ISSN: 1087-2108
CID: 2494602

Cutis verticis gyrate

Yagerman, S; Callahan, S; Terushkin, V; Meehan, S A; Pomeranz, M K; Friedman-Kien, A
Cutis verticis gyrata that involves only the face is a rare presentation of this even rarer cutaneous anomaly. We present a 61-year-old man, who developed primary essential progressive cutis verticis gyrata of the face.
ISSN: 1087-2108
CID: 2396992

Growth-Curve Modeling of Nevi With a Peripheral Globular Pattern

Bajaj, Shirin; Dusza, Stephen W; Marchetti, Michael A; Wu, Xinyuan; Fonseca, Maira; Kose, Kivanc; Brito, Johanna; Carrera, Cristina; Martins de Silva, Vanessa P; Malvehy, Josep; Puig, Susana; Yagerman, Sarah; Liebman, Tracey N; Scope, Alon; Halpern, Allan C; Marghoob, Ashfaq A
Importance: Although nevi with a peripheral rim of globules (peripheral globular nevi [PGN]) observed with dermoscopy are associated with enlarging melanocytic nevi, their actual growth dynamics remain unknown. Because change is a sensitive but nonspecific marker for melanoma, beginning to understand the growth patterns of nevi may improve the ability of physicians to differentiate normal from abnormal growth and reduce unnecessary biopsies. Objective: To study the growth dynamics and morphologic evolution of PGN on dermoscopy. Design, Setting, and Participants: A total of 84 participants with 121 PGN from September 1, 1999, through May 1, 2013, were identified retrospectively. Cohorts were recruited from the Memorial Sloan Kettering Cancer Center; Melanoma Unit of the Hospital Clinic, University of Barcelona; and Study of Nevi in Children. All 3 cohorts underwent longitudinal monitoring with serial dermoscopic imaging of their PGN. Data analysis was performed from May 1, 2014, through April 1, 2015. Main Outcomes and Measures: Establishment of the natural growth curve of PGN. The secondary aim was to establish the median time to growth cessation in those PGN for which the size eventually stabilized and/or had begun to decrease during the study period. Results: The median duration of follow-up was 25.1 (range, 2.0-114.4) months. Most of the nevi (116 [95.9%]) enlarged at some point during sequential monitoring. The rate of increase in the surface area of PGN varied among cohorts and ranged from -0.47 to 2.26 mm2/mo (mean rate, 0.25 [95% CI, 0.14-0.36] mm2/mo). The median time to growth cessation in the 26 PGN that stabilized or decreased in size (21.5%) was 58.6 months. All lesions changed in a symmetric manner and 91 (75.2%) displayed a decrease in the density of peripheral globules over time. Conclusions and Relevance: Nevi displaying a peripheral globular pattern enlarged symmetrically with apparent growth cessation occurring during a span of 4 to 5 years. Our results reiterate the important concept that not all growth is associated with malignancy.
PMID: 26287475
ISSN: 2168-6084
CID: 2180452

Feasibility and Efficacy of Patient-Initiated Mobile Teledermoscopy for Short-term Monitoring of Clinically Atypical Nevi

Wu, Xinyuan; Oliveria, Susan A; Yagerman, Sarah; Chen, Lucy; DeFazio, Jennifer; Braun, Ralph; Marghoob, Ashfaq A
IMPORTANCE/OBJECTIVE:Patient-driven mobile teledermoscopy may be applicable for monitoring of skin lesions. OBJECTIVE:To assess the feasibility, efficacy, and patient receptivity of teledermoscopy for short-term monitoring of clinically atypical nevi. DESIGN, SETTING, AND PARTICIPANTS/METHODS:This was a prospective cohort study performed at an institutional referral center in New York. Consecutive patients 18 years or older, with 1 or more clinically atypical nevi that required short-term monitoring and were accessible by a mobile imaging device were recruited for the study. All 34 patients consented to the study, and 29 completed follow-up. Dermoscopic images were obtained in the office-based setting by a dermatologist and with an iPhone by the patient at baseline and follow-up (3-4 months). Patients completed surveys that included questions about skincare awareness and attitudes toward teledermoscopy. Standard dermoscopic images were evaluated by the office-based dermatologist, and mobile dermoscopic images were sent via the Internet to a teledermatologist to evaluate image quality and presence of significant clinical lesion change. The decisions of the teledermatologist and office-based dermatologist were compared. MAIN OUTCOMES AND MEASURES/METHODS:(1) Feasibility of using mobile dermatoscope by patients, (2) diagnostic concordance of teledermoscopy vs conventional office-based visit, and (3) patient receptivity to teledermoscopy for short-term monitoring of nevi. RESULTS:Of the 29 patients who completed the study, 28 (97%) were able to acquire baseline and follow-up images that were subsequently deemed evaluable by the teledermatologist. The diagnostic concordance between conventional office-based visits and teledermoscopy encounters was 0.87 (SE, 0.13) (κ statistic). In addition, patients reported high receptivity to teledermoscopy for short-term monitoring of nevi. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Results from this pilot study suggest that teledermoscopy is feasible and effective as a method for short-term monitoring of clinically atypical nevi. The implementation of teledermoscopy can potentially enhance patient convenience, optimize physician scheduling, and promote efficiency.
PMID: 25629626
ISSN: 2168-6084
CID: 4483562