Oral prion neuroinvasion occurs independently of PrPC expression in the gut epithelium

The early replication of certain prion strains within Peyer’s patches in the small intestine is essential for the efficient spread of disease to the brain after oral exposure. Our data show that orally acquired prions utilize specialized gut epithelial cells known as M cells to enter Peyer’s patches. M cells express the cellular isoform of the prion protein, PrPC, and this may be exploited by some pathogens as an uptake receptor to enter Peyer’s patches. This suggested that PrPC might also mediate the uptake and transfer of prions across the gut epithelium into Peyer’s patches in order to establish infection. Furthermore, the expression level of PrPC in the gut epithelium could influence the uptake of prions from the lumen of the small intestine. To test this hypothesis, transgenic mice were created in which deficiency in PrPC was specifically restricted to epithelial cells throughout the lining of the small intestine. Our data clearly show that efficient prion neuroinvasion after oral exposure occurred independently of PrPC expression in small intestinal epithelial cells. The specific absence of PrPC in the gut epithelium did not influence the early replication of prions in Peyer’s patches or disease susceptibility. Acute mucosal inflammation can enhance PrPC expression in the intestine, implying the potential to enhance oral prion disease pathogenesis and susceptibility. However, our data suggest that the magnitude of PrPC expression in the epithelium lining the small intestine is unlikely to be an important factor which influences the risk of oral prion disease susceptibility. IMPORTANCE The accumulation of orally acquired prions within Peyer’s patches in the small intestine is essential for the efficient spread of disease to the brain. Little is known of how the prions initially establish infection within Peyer’s patches. Some gastrointestinal pathogens utilize molecules, such as the cellular prion protein PrPC, expressed on gut epithelial cells to enter Peyer’s patches. Acute mucosal inflammation can enhance PrPC expression in the intestine, implying the potential to enhance oral prion disease susceptibility. We used transgenic mice to determine whether the uptake of prions into Peyer’s patches was dependent upon PrPC expression in the gut epithelium. We show that orally acquired prions can establish infection in Peyer’s patches independently of PrPC expression in gut epithelial cells. Our data suggest that the magnitude of PrPC expression in the epithelium lining the small intestine is unlikely to be an important factor which influences oral prion disease susceptibility

The Development of School Psychology Assessment Centers as Training, Service Delivery, and Research Sites

School Psychologists have an ongoing responsibility to promote and support healthy schools, families, and communities, while contributing to knowledge, research, teaching, and supervision. Consequently, School Psychology programs should seek to meet these goals by providing their students with opportunities to engage in research and effective service delivery, participate in outreach services, and continued professional development. During Fall of 2013, faculty, students, and personnel of the School Psychology Program at Stephen F. Austin State University successfully developed a School Psychology Assessment Center, which is maintained on the university’s campus. The primary objective of this university-approved Center is the enhancement of service delivery to the on-campus student population and surrounding community and positive impact on training and professional development of masters and doctoral-level School Psychology trainees. This article describes the steps involved in the development and maintenance of School Psychology Assessment Centers

Total versus superficial parotidectomy for stage III melanoma

BackgroundThe primary purpose of this study was to describe the parotid recurrence rates after superficial and total parotidectomy.MethodsA retrospective cohort study was performed on patients with cutaneous melanoma metastatic to the parotid gland who underwent parotidectomy from 1998 through 2014. Primary outcome was parotid bed recurrence. Secondary outcomes were facial nerve function postoperatively and at last follow‐up.ResultsOne hundred twenty‐nine patients were included in the study. Thirty‐four patients (26%) underwent a total parotidectomy and 95 patients underwent superficial parotidectomy. Twelve patients (13%) developed parotid bed recurrence after superficial parotidectomy alone versus zero after total parotidectomy (P = .035). Facial nerve function, clinically detected disease, stage, and adjuvant treatment were not statistically different between the groups (P = .32, .32, .13, and 0.99, respectively).ConclusionParotid bed melanoma recurrence was more common after superficial parotidectomy compared to total parotidectomy, and recurrence resulted in significant facial nerve functional deficit. Our results support total parotidectomy when metastatic melanoma involves the parotid nodal basin.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137735/1/hed24810_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137735/2/hed24810.pd

Cranial nerve outcomes in regionally recurrent head & neck melanoma after sentinel lymph node biopsy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/156007/1/lary28243.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156007/2/lary28243_am.pd

The in vitro effects of resistin on the innate immune signaling pathway in isolated human subcutaneous adipocytes

Context: Obesity-associated inflammation is a contributory factor in the pathogenesis of type 2 diabetes mellitus (T2DM); the mechanisms underlying the progression to T2DM are unclear. The adipokine resistin has demonstrated pro-inflammatory properties in relation to obesity and T2DM. Objective: To characterize resistin expression in human obesity and address the role of resistin in the innate immune pathway. Furthermore, examine the influence of lipopolysaccharide, recombinant human resistin (rhResistin), insulin and rosiglitazone in human adipocytes. Finally, analyze the effect of rhResistin on the expression of components of the NF-κB pathway and insulin signaling cascade. Methods: Abdominal subcutaneous adipose tissue was obtained from patients undergoing elective liposuction surgery (n = 35, aged: 36-49 yr; BMI: 26.5 ± 5.9 kg/m2). Isolated adipocytes were cultured with rhResistin (10-50 ng/ml). The level of cytokine secretion from isolated adipocytes was examined by ELISA. The effect of rhResistin on protein expression of components of the innate immune pathway was examined by Western blot. Results: In-vitro studies demonstrated that antigenic stimuli increase resistin secretion (P < 0.001) from isolated adipocytes. Pro-inflammatory cytokine levels were increased in response to rhResistin (P < 0.001); this was attenuated by rosiglitazone (P < 0.01). When examining components of the innate immune pathway, rhResistin stimulated Toll-like receptor-2 protein expression. Similarly, mediators of the insulin signaling pathway, phosphospecific JNK1 and JNK2, were upregulated in response to rhResistin. Conclusion: Resistin may participate in more than one mechanism to influence pro-inflammatory cytokine release from human adipocytes; potentially via the integration of NF-κB and JNK signaling pathways

The natural history of thin melanoma and the utility of sentinel lymph node biopsy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141184/1/jso24765_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141184/2/jso24765.pd

Dry Climate Disconnected the Laurentian Great Lakes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94725/1/eost16649.pd

Localisation of citrullinated proteins in normal appearing white matter and lesions in the central nervous system in multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease, considered to be autoimmune in origin. Post-translational modification of central nervous system proteins, including glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP), through citrullination of arginine residues, may lead to exposure of neoepitopes, triggering autoimmunity. Here we investigated the expression of citrullinated proteins in active MS lesions, MS normal appearing white matter and control brain white matter. We demonstrate increased citrullinated GFAP and MBP by immunohistochemistry and western blotting in areas of ongoing demyelination, suggesting a pivotal role for deimination of GFAP and MBP in MS pathogenesis MS

Variants at APOE influence risk of deep and lobar intracerebral hemorrhage

Objective Prior studies investigating the association between APOE alleles ε2/ε4 and risk of intracerebral hemorrhage (ICH) have been inconsistent and limited to small sample sizes, and did not account for confounding by population stratification or determine which genetic risk model was best applied. Methods We performed a large-scale genetic association study of 2189 ICH cases and 4041 controls from 7 cohorts, which were analyzed using additive models for ε2 and ε4. Results were subsequently meta-analyzed using a random effects model. A proportion of the individuals (322 cases, 357 controls) had available genome-wide data to adjust for population stratification. Results Alleles ε2 and ε4 were associated with lobar ICH at genome-wide significance levels (odds ratio [OR] = 1.82, 95% confidence interval [CI] = 1.50–2.23, p = 6.6 × 10 −10 ; and OR = 2.20, 95%CI = 1.85–2.63, p = 2.4 × 10 −11 , respectively). Restriction of analysis to definite/probable cerebral amyloid angiopathy ICH uncovered a stronger effect. Allele ε4 was also associated with increased risk for deep ICH (OR = 1.21, 95% CI = 1.08–1.36, p = 2.6 × 10 −4 ). Risk prediction evaluation identified the additive model as best for describing the effect of APOE genotypes. Interpretation APOE ε2 and ε4 are independent risk factors for lobar ICH, consistent with their known associations with amyloid biology. In addition, we present preliminary findings on a novel association between APOE ε4 and deep ICH. Finally, we demonstrate that an additive model for these APOE variants is superior to other forms of genetic risk modeling previously applied. ANN NEUROL 2010Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78478/1/22134_ftp.pd