Exploring longitudinal associations between neighborhood disadvantage and cortisol levels in early childhood.

Children who grow up in poverty are more likely to experience chronic stressors that generate "wear" on stress regulatory systems including the hypothalamus-pituitary-adrenal (HPA) axis. This can have long-term consequences for health and well-being. Prior research has examined the role of proximal family and home contributions to HPA axis functioning. However, there is evidence to suggest that more distal levels of context, including neighborhoods, also matter. Prior evidence has primarily focused on adolescents and adults, with little evidence linking the neighborhood context with HPA activity in infancy and toddlerhood. We tested whether neighborhood disadvantage (indexed by US Census data) was associated with basal salivary cortisol levels at 7, 15, and 24 months of child age in a large sample of families (N = 1,292) residing in predominately low-income and rural communities in the United States. Multilevel models indicated that neighborhood disadvantage was positively associated with salivary cortisol levels and that this effect emerged across time. This effect was moderated by the race/ethnicity of children such that the association was only observed in White children in our sample. Findings provide preliminary evidence that the neighborhood context is associated with stress regulation during toddlerhood, elucidating a need for future work to address possible mechanisms.

Trajectories of Discrimination Across Adolescence: Associations With Academic, Psychological, and Behavioral Outcomes.

The authors explored trajectories of perceived discrimination over a 6-year period (five assessments in 6th-11th grade) in relation to academic, behavioral, and psychological adjustment in 8th and 11th grades. They distinguished discrimination from adults versus peers in addition to overt versus covert discrimination from peers. The sample included 226 African American, White, Dominican, Puerto Rican, and Chinese adolescents (ages 11-12 at Time 1) recruited in sixth grade from six public schools in New York City. All forms of discrimination increased during middle school and decreased during high school. The frequency with which adolescents reported different sources and types of discrimination varied across ethnicity/race, but not gender. Initial levels and rates of change in discrimination predicted academic, behavioral, and psychological adjustment in 8th and 11th grades, albeit in complex ways.

Comparison of margin status and lesional size between radioactive seed localized vs conventional wire localized breast lumpectomy specimens.

Despite the known benefits of the use of radioactive seed localization (RSL), few studies have looked at the resultant pathologic marginal status of these lumpectomy specimens, especially in regard to different definitions of close/positive margins. We compared the marginal status of lumpectomy specimens removed by either RSL or conventional wire localization (CWL) techniques. A total of 106 lumpectomy specimens including 62 by CWL and 44 by RSL for invasive ductal and lobular carcinomas were compared. Data on gross and microscopic surgical margin status, tumor type and grade, and demographic information were retrospectively collected. There was no difference between the techniques in terms of tumor characteristics including size, histologic grade, lymph node positivity, or age. Although the distributions are very similar between CWL and RSL specimens for final marginal assessments (P=.69), there is a (modest) statistically significant difference in the distribution for margin classifications based on gross assessments (P=.040), specifically more RSL specimens exhibiting tumor within 1mm of the closest margin. Concordance between gross and microscopic lesion measurements is highest for invasive ductal carcinoma grade 3 for both CWL and RSL lumpectomies (78.6% and 80.0%). This study shows that there were no significant marginal status differences between RSL and CWL lumpectomy specimens with invasive carcinoma. Rather, what was relevant is whether the entire specimen could be classified as having negative/close margins. Significant workflow challenges in surgical pathology laboratories are expected with the adoption of the RSL process.

Do We Know Where We Stand? Neighborhood Relative Income, Subjective Social Status, and Health.

Bridging research on relative income and subjective social status (SSS), this study examines how neighborhood relative income is related to ones' SSS, and in turn, physical and mental health. Using a survey sample of 1807 U.S. adults, we find that neighborhood median income significantly moderates the relationship between household income and self-reported physical and mental health. Low-income individuals living in high-income neighborhoods (i.e., relative disadvantage) report better physical and mental health than low-income individuals living in low-income neighborhoods. In addition, high-income individuals living in low-income neighborhoods (i.e., relative advantage) report higher SSS (relative to neighbors), whereas low-income individuals living in high-income neighborhoods (i.e., relative disadvantage) also report higher SSS. We draw from social comparison theory to interpret these results positing that downward comparisons may serve an evaluative function while upward comparisons may result in affiliation with better-off others. Finally, we demonstrate that SSS explains the relationship between neighborhood relative income and health outcomes, providing empirical support for the underlying influence of perceived social position.

The utility of liquid-based cytology in salivary gland fine-needle aspirates: experience of an academic institution.

OBJECTIVE: To review the morphological features of salivary gland fine-needle aspirates (FNA) on ThinPrep® (TP) preparations. Emphasis is placed on the commonalities and specific differences between TP and conventional smear (CS) preparations. STUDY DESIGN: The cytology and surgical pathology archives were searched for 'salivary' or 'parotid' at our institution from 2003 to 2013 for cases processed by TP and with a range of specified diagnoses and surgical follow-up. These cases were reviewed by the authors. A review of the known literature was also performed. RESULTS: Morphological features and artifacts were noted for the most common salivary gland lesions. General features noted in the literature were identified, along with novel features identified on our review of cases. Emphasis was placed on cellular alterations, extracellular differences and architectural changes. CONCLUSIONS: The multitude of both benign and malignant lesions coupled with the unique artifacts encountered on TP makes salivary gland FNAs difficult for most practicing pathologists and cytopathologists. For this reason, many laboratories have been reluctant to implement TP preparations for these lesions. With knowledge of the specific artifacts and differences on TP compared to CS, TP can be used with confidence without a compromise in diagnostic accuracy for adequately cellular samples.

Prion seeding activity and infectivity in skin samples from patients with sporadic Creutzfeldt-Jakob disease.

Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is transmissible through iatrogenic routes due to abundant infectious prions [misfolded forms of the prion protein (PrPSc)] in the central nervous system (CNS). Some epidemiological studies have associated sCJD risk with non-CNS surgeries. We explored the potential prion seeding activity and infectivity of skin from sCJD patients. Autopsy or biopsy skin samples from 38 patients [21 sCJD, 2 variant CJD (vCJD), and 15 non-CJD] were analyzed by Western blotting and real-time quaking-induced conversion (RT-QuIC) for PrPSc Skin samples from two patients were further examined for prion infectivity by bioassay using two lines of humanized transgenic mice. Western blotting revealed dermal PrPSc in one of five deceased sCJD patients and one of two vCJD patients. However, the more sensitive RT-QuIC assay detected prion seeding activity in skin from all 23 CJD decedents but not in skin from any non-CJD control individuals (with other neurological conditions or other diseases) during blinded testing. Although sCJD patient skin contained ~103- to 105-fold lower prion seeding activity than did sCJD patient brain tissue, all 12 mice from two transgenic mouse lines inoculated with sCJD skin homogenates from two sCJD patients succumbed to prion disease within 564 days after inoculation. Our study demonstrates that the skin of sCJD patients contains both prion seeding activity and infectivity, which raises concerns about the potential for iatrogenic sCJD transmission via skin.

Deconvoluting the functions of polypeptide N-alpha-acetylgalactosaminyltransferase family members by glycopeptide substrate profiling.

The polypeptide N-alpha-acetylgalactosaminyltransferases (ppGalNAcTs) play a key role in mucin-type O-linked glycan biosynthesis by installing the initial GalNAc residue on the protein scaffold. The preferred substrates and functions of the >20 isoforms in mammals are not well understood. However, current data suggest that glycosylated mucin domains are created by the successive, often hierarchical, action of several specific ppGalNAcTs. Herein we analyzed the glycopeptide substrate preferences of several ppGalNAcT family members using a library screening approach. A 56-member glycopeptide library designed to reflect a diversity of glycan clustering was assayed for substrate activity with ppGalNAcT isoforms using an azido-ELISA. The data suggest that the ppGalNAcTs can be classified into at least four types, which working together, are able to produce densely glycosylated mucin glycoproteins.

Role of peptide sequence and neighboring residue glycosylation on the substrate specificity of the uridine 5'-diphosphate-alpha-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyl transferases T1 and T2: kinetic modeling of the porcine and canine submaxillary gland mucin tandem repeats.

A large family of uridine 5'-diphosphate (UDP)-alpha-N-acetylgalactosamine (GalNAc):polypeptide N-acetylgalactosaminyl transferases (ppGalNAc Ts) initiates mucin-type O-glycan biosynthesis at serine and threonine. The peptide substrate specificities of individual family members are not well characterized or understood, leaving an inability to rationally predict or comprehend sites of O-glycosylation. Recently, a kinetic modeling approach demonstrated neighboring residue glycosylation as a major factor modulating the O-glycosylation of the porcine submaxillary gland mucin 81 residue tandem repeat by ppGalNAc T1 and T2 [Gerken et al. (2002) J. Biol. Chem. 277, 49850-49862]. To confirm the general applicability of this model and its parameters, the ppGalNAc T1 and T2 glycosylation kinetics of the 80+ residue tandem repeat from the canine submaxillary gland mucin was obtained and characterized. To reproduce the glycosylation patterns of both mucins (comprising 50+ serine/threonine residues), specific effects of neighboring peptide sequence, in addition to the previously described effects of neighboring residue glycosylation, were required of the model. Differences in specificity of the two transferases were defined by their sensitivities to neighboring proline and nonglycosylated hydroxyamino acid residues, from which a ppGalNAc T2 motif was identified. Importantly, the model can approximate the previously reported ppGalNAc T2 glycosylation kinetics of the IgA1 hinge domain peptide [Iwasaki, et al. (2003) J. Biol. Chem. 278, 5613-5621], further validating both the approach and the ppGalNAc T2 positional weighting parameters. The characterization of ppGalNAc transferase specificity by this approach may prove useful for the search for isoform-specific substrates, the creation of isoform-specific inhibitors, and the prediction of mucin-type O-glycosylation sites.