Identification of cellular and noncellular components of mature intact human peripheral nerve.

BACKGROUND AND AIMS: The goal of this study was to define basic constituents of the adult peripheral nervous system (PNS) using intact human nerve tissues. METHODS: We combined fluorescent and chromogenic immunostaining methods, myelin-selective fluorophores, and routine histological stains to identify common cellular and noncellular elements in aldehyde-fixed nerve tissue sections. We employed Schwann cell (SC)-specific markers, such as S100ß, NGFR, Sox10, and myelin protein zero (MPZ), together with axonal, extracellular matrix (collagen IV, laminin, fibronectin), and fibroblast markers to assess the SC's relationship to myelin sheaths, axons, other cell types, and the acellular environment. RESULTS: Whereas S100ß and Sox10 revealed mature SCs in the absence of other stains, discrimination between myelinating and non-myelinating (Remak) SCs required immunodetection of NGFR along with axonal and/or myelin markers. Surprisingly, our analysis of NGFR+ profiles uncovered the existence of at least 3 different novel populations of NGFR+/S100ß- cells, herein referred to as nonglial cells, residing in the stroma and perivascular areas of all nerve compartments. An important proportion of the nerve's cellular content, including circa 30% of endoneurial cells, consisted of heterogenous S100ß negative cells that were not associated with axons. Useful markers to identify the localization and diversity of nonglial cell types across different compartments were Thy1, CD34, SMA, and Glut1, a perineurial cell marker. INTERPRETATION: Our optimized methods revealed additional detailed information to update our understanding of the complexity and spatial orientation of PNS-resident cell types in humans.

Diversity in Hand Surgery Leadership: The Impact of Mentorship and Bias.

BACKGROUND: Diversity in leadership drives innovation. However, underrepresented minorities may face barriers. The aim of this study is to understand the impact of gender and race on the experience of leaders in hand surgery. METHODS: An anonymous survey was sent to leaders in hand surgery who attained the position of national society president, head of a division/department, or hand fellowship director. The survey assessed demographic information, grit, mentorship, and bias. RESULTS: One hundred twenty-one leaders responded for a response rate of 60.5%. Men represented 81.0% and women 19.0%. Most respondents were white (87.6%) with 7% Asian and 6% any other race. Ninety-one percent of female respondents lived in a dual career household, compared with 53.7% of male respondents (odds ratio [OR] 0.15, P = .017). Female respondents had significantly higher grit compared with male respondents (4.3 vs 4.0, P = .050). Male respondents were more likely to have a male mentor/sponsor than women (95% vs 76%, respectively, P = .001). White respondents were more likely to have a white mentor/sponsor than nonwhite respondents (91% vs 61%, respectively, P = .009). Ninety-five percent of women reported experiencing bias compared with 27% of men (P < .001). Specifically, women reported bias in salary, promotion, nomination, sponsorship, networking, and clinical resources. Nonwhite respondents were significantly more likely to experience bias in promotion (P = .006). CONCLUSIONS: Women and racial minorities face bias and barriers to leadership within hand surgery.

EphA2 Expression Regulates Inflammation and Fibroproliferative Remodeling in Atherosclerosis.

BACKGROUND: Atherosclerotic plaque formation results from chronic inflammation and fibroproliferative remodeling in the vascular wall. We previously demonstrated that both human and mouse atherosclerotic plaques show elevated expression of EphA2, a guidance molecule involved in cell-cell interactions and tumorigenesis. METHODS: Here, we assessed the role of EphA2 in atherosclerosis by deleting EphA2 in a mouse model of atherosclerosis (Apoe-/-) and by assessing EphA2 function in multiple vascular cell culture models. After 8 to 16 weeks on a Western diet, male and female mice were assessed for atherosclerotic burden in the large vessels, and plasma lipid levels were analyzed. RESULTS: Despite enhanced weight gain and plasma lipid levels compared with Apoe-/- controls, EphA2-/-Apoe-/- knockout mice show diminished atherosclerotic plaque formation, characterized by reduced proinflammatory gene expression and plaque macrophage content. Although plaque macrophages express EphA2, EphA2 deletion does not affect macrophage phenotype, inflammatory responses, and lipid uptake, and bone marrow chimeras suggest that hematopoietic EphA2 deletion does not affect plaque formation. In contrast, endothelial EphA2 knockdown significantly reduces monocyte firm adhesion under flow. In addition, EphA2-/-Apoe-/- mice show reduced progression to advanced atherosclerotic plaques with diminished smooth muscle and collagen content. Consistent with this phenotype, EphA2 shows enhanced expression after smooth muscle transition to a synthetic phenotype, and EphA2 depletion reduces smooth muscle proliferation, mitogenic signaling, and extracellular matrix deposition both in atherosclerotic plaques and in vascular smooth muscle cells in culture. CONCLUSIONS: Together, these data identify a novel role for EphA2 in atherosclerosis, regulating both plaque inflammation and progression to advanced atherosclerotic lesions. Cell culture studies suggest that endothelial EphA2 contributes to atherosclerotic inflammation by promoting monocyte firm adhesion, whereas smooth muscle EphA2 expression may regulate the progression to advanced atherosclerosis by regulating smooth muscle proliferation and extracellular matrix deposition.

Revisiting racial disparities in access to surgical management of drug-resistant temporal lobe epilepsy post implementation of Affordable Care Act.

OBJECTIVES: Prior to enactment of the Affordable Care Act(ACA), several reports demonstrated remarkable racial disparities in access to surgical care for epileptic patients. Implementation of ACA provided healthcare access to 7-16 million uninsured Americans. The current study investigates racial disparity post ACA era in (1) access to surgical management of drug-resistant temporal lobe epilepsy (DRTLE); (2) short-term outcomes in the surgical cohort. PATIENT AND METHODS: Adult patients with DRTLE registered in the National Inpatient Sample (2012-2013) were identified. Association of race (African Americans and other minorities with respect to Caucasians) with access to surgical management of TLE, and short-term outcomes [discharge disposition, length of stay (LOS) and hospital charges] in the surgical cohort were investigated using multivariable regression techniques. RESULTS: Of the 4062 patients with DRTLE, 3.6%(n=148) underwent lobectomy. Overall, the mean age of the cohort was 42.35±16.33years, and 54% were female. Regression models adjusted for patient demographics, clinical and hospital characteristics demonstrated no racial disparities in access to surgical care for DRTLE. Likewise, no racial disparity was noted in outcomes in the surgical cohort. CONCLUSION: Our study reflects no racial disparity in access to surgical care in patients with DRTLE post 2010 amendment of the ACA. The seismic changes to the US healthcare system may plausibly have accounted for addressing the gap in racial disparity for epilepsy surgery.

Creutzfeldt-Jakob disease: updated diagnostic criteria, treatment algorithm, and the utility of brain biopsy.

Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative condition with a rapid disease course and a mortality rate of 100%. Several forms of the disease have been described, and the most common is the sporadic type. The most challenging aspect of this disease is its diagnosis-the gold standard for definitive diagnosis is considered to be histopathological confirmation-but newer tests are providing means for an antemortem diagnosis in ways less invasive than brain biopsy. Imaging studies, electroencephalography, and biomarkers are used in conjunction with the clinical picture to try to make the diagnosis of CJD without brain tissue samples, and all of these are reviewed in this article. The current diagnostic criteria are limited; test sensitivity and specificity varies with the genetics of the disease as well as the clinical stage. Physicians may be unsure of all diagnostic testing available, and may order outdated tests or prematurely request a brain biopsy when the diagnostic workup is incomplete. The authors review CJD, discuss the role of brain biopsy in this patient population, provide a diagnostic pathway for the patient presenting with rapidly progressive dementia, and propose newer diagnostic criteria.