Publications

Mesenchymal stem/stromal cells (MSCs) play crucial roles in maintaining tissue homeostasis during physiological turnovers and injuries. Very little is known about the phenotype, distribution and molecular nature of MSCs in freshly isolated human salivary glands (SGs) as most reports have focused on the analysis of cultured MSCs. Our results demonstrate that the cell adhesion molecule CD34 was widely expressed by the MSCs of human major SGs, namely parotid (PAG), sublingual (SLG) and submandibular (SMG) glands. Further, gene expression analysis of CD34 cells derived from fetal SMGs showed significant upregulation of genes involved in cellular adhesion, proliferation, branching, extracellular matrix remodeling and organ development. Moreover, CD34 SMG cells exhibited elevated expression of genes encoding extracellular matrix, basement membrane proteins, and members of ERK, FGF and PDGF signaling pathways, which play key roles in glandular development, branching and homeostasis. In vitro CD34 cell derived SG-MSCs revealed multilineage differentiation potential. Intraglandular transplantation of cultured MSCs in immunodeficient mice led to their engraftment in the injected and uninjected contralateral and ipsilateral glands. Engrafted cells could be localized to the stroma surrounding acini and ducts. In summary, our data show that CD34 derived SG-MSCs could be a promising cell source for adoptive cell-based SG therapies, and bioengineering of artificial SGs.

OBJECTIVES

To examine how dual coverage for nonelderly, low-income veterans by Veterans Affairs (VA) and Medicaid affects their demand for care.

DATA SOURCES

Veterans Affairs utilization data and Medicaid Analytic Extract Files.

STUDY DESIGN

A retrospective, longitudinal study of VA users prior to and following enrollment in Medicaid 2006-2010.

DATA COLLECTION/EXTRACTION METHODS

Veterans Affairs reliance, or proportion of care provided by VA, was estimated with beta-binomial models, adjusting for patient and state Medicaid program factors.

PRINCIPAL FINDINGS

In a cohort of 19,890 nonelderly veterans, VA utilization levels were similar before and after enrolling in Medicaid. VA outpatient reliance was 0.65, and VA inpatient reliance was 0.53 after Medicaid enrollment. Factors significantly associated with greater VA reliance included sociodemographic factors, having a service-connected disability, comorbidity, and higher state Medicaid reimbursement. Factors significantly associated with less VA reliance included months enrolled in Medicaid, managed care enrollment, Medicaid eligibility type, longer drive time to VA care, greater Medicaid eligibility generosity, and better Medicaid quality.

CONCLUSION

Veterans Affairs utilization following new Medicaid enrollment remained relatively unchanged, and the VA continued to provide the large majority of care for dually enrolled veterans. There was variation among patients as Medicaid eligibility and other program factors influenced their use of Medicaid services.

Hepatitis E virus (HEV) infection uncommonly causes chronic hepatitis and neurologic disease. We describe a case of genotype 3a HEV meningoencephalitis diagnosed by metagenomic next-generation sequencing, illustrating the power of an unbiased molecular approach to microbial testing and the first reported case of HEV infection presumably acquired through lung transplantation.

Neurons expressing agouti-related protein (AgRP) are essential for feeding. The majority of these neurons are located outside the blood-brain barrier (BBB), allowing them to directly sense circulating metabolic factors. Here, we show that, in adult mice, AgRP neurons outside the BBB (AgRP) were rapidly ablated by peripheral administration of monosodium glutamate (MSG), whereas AgRP neurons inside the BBB and most proopiomelanocortin (POMC) neurons were spared. MSG treatment induced proliferation of tanycytes, the putative hypothalamic neural progenitor cells, but the newly proliferated tanycytes did not become neurons. Intriguingly, AgRP neuronal number increased within a week after MSG treatment, and newly emerging AgRP neurons were derived from post-mitotic cells, including some from the Pomc-expressing cell lineage. Our study reveals that the lack of protection by the BBB renders AgRP vulnerable to lesioning by circulating toxins but that the rapid re-emergence of AgRP is part of a reparative process to maintain energy balance.

IMPORTANCE

Asthma is a multifactorial disease composed of endotypes with varying risk profiles and outcomes. African Americans experience a high burden of asthma and of psychosocial stress, including racial discrimination. It is unknown which endotypes of asthma are vulnerable to racial/ethnic discrimination.

OBJECTIVE

We examined the association between self-reported racial/ethnic discrimination and bronchodilator response (BDR) among African American youth with asthma ages 8 to 21 years (n = 576) and whether this association varies with tumor necrosis factor alpha (TNF-α) level.

MATERIALS AND METHODS

Self-reported racial/ethnic discrimination was assessed by a modified Experiences of Discrimination questionnaire as none or any. Using spirometry, BDR was specified as the mean percentage change in forced expiratory volume in one second before and after albuterol administration. TNF-α was specified as high/low levels based on our study population mean. Linear regression was used to examine the association between self-reported racial/ethnic discrimination and BDR adjusted for selected characteristics. An interaction term between TNF-α levels and self-reported racial/ethnic discrimination was tested in the final model.

RESULTS

Almost half of participants (48.8%) reported racial/ethnic discrimination. The mean percent BDR was higher among participants reporting racial/ethnic discrimination than among those who did not (10.8 versus 8.9, p = 0.006). After adjustment, participants reporting racial/ethnic discrimination had a 1.7 (95% CI: 0.36-3.03) higher BDR mean than those not reporting racial/ethnic discrimination. However, we found heterogeneity of this association according to TNF-α levels (p-interaction = 0.040): Among individuals with TNF-α high level only, we observed a 2.78 higher BDR mean among those reporting racial/ethnic discrimination compared with those not reporting racial/ethnic discrimination (95%CI: 0.79-4.77).

CONCLUSIONS

We found BDR to be increased in participants reporting racial/ethnic discrimination and this association was limited to African American youth with TNF-α high asthma, an endotype thought to be resistant to traditional asthma medications. These results support screening for racial/ethnic discrimination in those with asthma as it may reclassify disease pathogenesis.