Risk Factors for Basal Cell Carcinoma Among Patients With Basal Cell Nevus Syndrome: Development of a Basal Cell Nevus Syndrome Patient Registry.

IMPORTANCE: Patients with basal cell nevus syndrome (BCNS) have a greater risk of developing numerous basal cell carcinomas (BCCs). Risk factors influencing the wide variation in tumor burden are poorly understood. OBJECTIVE: To describe the burden of BCCs in patients with BCNS in the United States and identify potential risk factors for BCCs. DESIGN, SETTING, AND PARTICIPANTS: Prospective clinical registry with data collected from September 2014 to March 2016. Participants were recruited from a mailing list of patients with BCNS at Children's Hospital Oakland Research Institute and Basal Cell Carcinoma Nevus Syndrome Life Support Network. Patients of all ages with a diagnosis of BCNS were eligible for enrollment. Participants completed a clinical questionnaire on their disease characteristics and risk factors. MAIN OUTCOMES AND MEASURES: Number of BCCs in the past 2 years and over lifetime (disease burden), risk factors for BCCs. RESULTS: A consecutive sample of the first 141 participants was included (34% [100 of 297] response rate from paper survey, 23% [41 of 179] from online survey; 85 [60%] female; mean age at start of study, 53 [range, 8-83] years; 131 [93%] white). In the previous 2 years, participants reported a mean of 25 BCCs (median, 11; range, 0-250). Over their lifetime, participants reported a mean of 257 BCCs (median, 160; range, 0-2200). Univariate analysis identified age (odds ratio [OR], 1.05; 95% CI, 1.03-1.07; P < .001), number of sunburns (OR, 1.05; 95% CI, 1.00-1.10; P = .047), and history of radiation exposure (OR, 2.26; 95% CI, 1.02-5.03; P = .046) as potential risk factors for lifetime BCC severity. On multivariate analysis, only age (OR, 1.04; 95% CI, 1.02-1.07; P < .001) and number of sunburns (OR, 1.06; 95% CI, 1.00-1.11; P = .04) were statistically significant. In our adjusted models, BCC burden increased by 4% per year of age and by 6% per number of sunburns. CONCLUSIONS AND RELEVANCE: Patients with BCNS have a high burden of BCCs. Age and number of sunburns were significantly associated with the severity of lifetime BCC. Further interventions to prevent and treat BCCs in patients with BCNS are needed.

Occupationally related contact dermatitis in North American food service workers referred for patch testing, 1994 to 2010.

BACKGROUND: Contact dermatoses are common in food service workers (FSWs). OBJECTIVES: This study aims to (1) determine the prevalence of occupationally related contact dermatitis among FSWs patch tested by the North American Contact Dermatitis Group (NACDG) and (2) characterize responsible allergens and irritants as well as sources. METHODS: Cross-sectional analysis of patients patch tested by the NACDG, 1994 to 2010, was conducted. RESULTS: Of 35,872 patients patch tested, 1237 (3.4%) were FSWs. Occupationally related skin disease was significantly more common in FSWs when compared with employed non-FSWs. Food service workers were significantly more likely to have hand (P < 0.0001) and arm (P < 0.0006) involvement. The rates for irritant and allergic contact dermatitis in FSWs were 30.6% and 54.7%, respectively. Although the final diagnosis of irritant contact dermatitis was statistically higher in FSWs as compared with non-FSWs, allergic contact dermatitis was lower in FSWs as compared with non-FSWs. The most frequent currently relevant and occupationally related allergens were thiuram mix (32.5%) and carba mix (28.9%). Gloves were the most common source of responsible allergens. The NACDG standard tray missed at least 1 occupationally related allergen in 38 patients (4.3%). CONCLUSIONS: Among FSWs patch tested by the NACDG between 1994 and 2010, the most common allergens were thiuram mix and carba mix. Gloves were the most common source of responsible allergens.

Contribution of macromolecular structure to the retention of low-density lipoprotein at arterial branch points.

BACKGROUND: Extracellular deposition of low-density lipoprotein (LDL) in the arterial wall is an essential early step in atherosclerosis. This process preferentially occurs at arterial branch points, reflecting a regional variation in lipoprotein-arterial wall interactions. In this study, we characterized the submicron microstructure of arterial wall collagen and elastin to evaluate its potential role in regional LDL deposition. METHODS AND RESULTS: With 2-photon microscopy, we used the intrinsic optical properties of collagen and elastin to determine the arterial wall macromolecular microstructure in fresh porcine and murine arteries. This optical approach generated unique nondestructive en face 3-dimensional views of the wall. The collagen/elastin microstructure was found to vary with the topology of the arterial bed. A nearly confluent elastin surface layer was present throughout but was missing at atherosclerosis-susceptible branch points, exposing dense collagen-proteoglycan complexes. In LDL binding studies, this luminal elastin layer limited LDL penetration, whereas its absence at the branches resulted in extensive LDL binding. Furthermore, LDL colocalized with proteoglycans with a sigmoidal dose dependence (inflection point, approximately 130 mg LDL/dL). Ionic strength and competing anions studies were consistent with the initial interaction of LDL with proteoglycans to be electrostatic in nature. CONCLUSIONS: This optical sectioning approach provided a robust 3-dimensional collagen/elastin microstructure of the arterial wall in fresh samples. At atherosclerosis-susceptible vascular branch points, the absence of a luminal elastin barrier and the presence of a dense collagen/proteoglycan matrix contribute to increased retention of LDL.

Efficient estimation of retinal ganglion cell number: a stereological approach.

Retinal ganglion cells (RGCs) are the only output neurons of the retina, and their degeneration after damage to the optic nerve or in glaucoma is a well established system for studying apoptosis in the central nervous system. Frequently used procedures for assessing RGC number in retinal flat mounts suffer from two problems: RGC densities are not uniform across retinal flat mounts, and density measures may therefore not reflect total number, and flat mounts do not allow efficient use of tissue. To overcome these problems we developed a stereological method for efficiently assessing RGC number in cryostat sections of the retina. We empirically demonstrate that only approximately 1:20 sections need be assessed to accurately estimate the total number of RGCs in the rat retina, providing ample tissue for additional studies in the same retina and saving considerably on more exhaustive sampling strategies. Using this method, we estimate that there are 86,282+/-4759 RGCs in the normal Brown Norway rat retina. These counts match well with estimates of axon counts in optic nerve. In a pilot study of experimental glaucoma, we determined a reduction of RGCs to 53,862+/-4272 (p<0.05). The current technique should prove advantageous to assess neuroprotective strategies in these experimental models.