The Ursinus Weekly, April 16, 1917

Varsity nine loses close game • Military training officially instituted • Hamilton Holt on Japan to-day • Zwinglian prize essay: The indifference of youth • First aid class • Seminary notes • Christian organizations • Literary societies • On the campus • Our spring birdshttps://digitalcommons.ursinus.edu/weekly/2589/thumbnail.jp

Effects of Partnerships between Adolescents with Developmental Disabilities and Service Dogs

Background: With increasing frequency, service dogs are being placed with children with developmental disabilities (DDs). Occupational therapists and other professionals have advocated for the therapeutic use of service dog partnerships to facilitate greater independence and quality of life. There are no studies that examine service dog intervention with adolescents. Method: This study focused on the effects of partnerships between service dogs and three participant dyads, each including an adolescent with DDs and a parent. A single-subject, alternating treatment design was used to compare the effects of two conditions (service dog present or not present). The effects were examined for adolescents’ anxiety behaviors during transitions and during grocery store shopping, for social interactions during grocery store shopping, and for parents’ reported levels of stress. Results: Findings were that service dog partnerships reduced the presence of anxiety behaviors during transitions for one of the three adolescents; reduced the presence of anxiety behaviors during grocery store visits for two of the three adolescents; increased social interactions for all three of the participant dyads; and had no meaningful impact on self-reported parental stress level. Conclusion: For adolescents with DDs, professionals may want to consider service dog partnerships to decrease anxiety behaviors and increase social interactions in the community

Mandibular and Neural Crest Cell Deficits Seen in TsDn65 Down Syndrome Mouse Model Rescued By Green Tea Polyphenol, EGCG

poster abstractDown Syndrome (DS) is caused by trisomy of the human chromosome 21 (Hsa21) and occurs in ~1 of every 700 births. DS is distinguished by over 80 phenotypic abnormalities including skeletal deficits and craniofacial phenotypes characterized by a flattened skull, slanted eyes, and a smaller mandible. To study these abnormalities, we utilize the Ts65Dn DS mouse model containing a triplication of approximately half of the gene homologues found on Hsa21 and mirrors the skeletal and mandibular phenotypes observed in DS. In Ts65Dn mice, the origin of the mandibular deficits were traced to a reduction in size of the 1st branchial arch (BA1), the developmental precursor to the mandible, occurring at embryonic day 9.5 (E9.5). At E9.5, we observe a lack of proliferation and migration of neural crest cells (NCC) from the neural tube (NT) into the BA1, causing a reduced BA1. We hypothesize that an overexpression of Dyrk1a, a Hsa21 homologue, contributes to the mandibular deficit seen in E9.5 Ts65Dn embryos. We propose that EGCG, a green tea polyphenol, will inhibit DYRK1a activity, rescuing the BA1 deficit. To test our hypothesis, Ts65Dn mothers were treated with EGCG from E0-E9.5 and sacrificed to retrieve the E9.5 embryos. Our results from unbiased stereological assessments show that E0-E9.5 EGCG in vivo treatment has the potential to increase NCC number, BA1 volume, and embryo volume of trisomic embryos. This data provide preclinical testing for a potential therapy of DS craniofacial disorders, which may extend to treating bone deficits in DS and osteoporosis

Treatment with a Green Tea Polyphenol Corrects Craniofacial Deficits Associated with Down Syndrome

poster abstractDown syndrome (DS) is caused by trisomy of human chromosome 21 (HSA21). Individuals with DS present craniofacial abnormalities including an undersized, dismorphic mandible leading to difficulty with eating, breathing, and swallowing. Using the Ts65Dn DS mouse model (three copies of ~50% HSA21 homologs), we have traced the mandibular deficit to a neural crest cell (NCC) deficiency and reduction in first pharyngeal arch (PA1 or mandibular precursor) size at embryonic day 9.5. At E9.5, Dyrk1A, a triplicated DS candidate gene, is overexpressed and may cause the NCC and PA1 deficits. We hypothesize that treatment of pregnant Ts65Dn mothers with Epigallocatechin gallate (EGCG), a known Dyrk1A inhibitor, will correct NCC deficits and rescue the undersized PA1 in trisomic E9.5 embryos. To test our hypothesis, we treated pregnant Ts65Dn mothers with EGCG from either E7-E8 or E0-E9.5. Our preliminary study found an increase in PA1 volume and NCC number in trisomic E9.5 embryos after treatment, but observed differences between treatment regimens. Differential gene expression was also quantified in trisomic treated embryos. This preliminary data suggests EGCG treatment has the potential to rescue the mandibular phenotype caused by trisomy. These findings provide preclinical testing for a potential therapy for craniofacial disorders linked to DS

Health-related quality of life in KEYNOTE-010 : a phase II/III study of pembrolizumab versus docetaxel in patients with previously treated advanced, programmed death ligand 1-expressing NSCLC

Introduction: In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1-expressing (tumor proportion score >= 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here. Methods: Patients were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks or docetaxel 75 mg/m(2) every 3 weeks. HRQoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30 (C30), EORTC QLQ-Lung Cancer 13 (LC13), and EuroQoL-5D. Key analyses included mean baseline-to-week-12 change in global health status (GHS)/quality of life (QoL) score, functioning and symptom domains, and time to deterioration in a QLQ-LC13 composite endpoint of cough, dyspnea, and chest pain. Results: Patient reported outcomes compliance was high across all three instruments. Pembrolizumab was associated with better QLQ-C30 GHS/QoL scores from baseline to 12 weeks than docetaxel, regardless of pembrolizumab dose or tumor proportion score status (not significant). Compared with docetaxel, fewer pembrolizumab-treated patients had "deteriorated" status and more had "improved" status in GHS/QoL. Nominally significant improvement was reported in many EORTC symptom domains with pembrolizumab, and nominally significant worsening was reported with docetaxel. Significant prolongation in true time to deterioration for the QLQ-LC13 composite endpoint emerged for pembrolizumab 10 mg/kg compared to docetaxel (nominal two-sided p = 0.03), but not for the 2-mg/kg dose. Conclusions: These findings suggest that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

The Lantern Vol. 15, No. 3, Summer 1947

• On Sleeping at Lectures • So You Want Security • Mild and Bitters • The Child April • Helgoland • His Majesty, Tabby • January Interval • A Friend or Two • Wish in June • The Search • Jack of 54 and Davey Jones • Song of the Earth • Donald Gay Baker • The Dilemma by the Horns • Psychologyhttps://digitalcommons.ursinus.edu/lantern/1042/thumbnail.jp

Endoscopic Assessment of the Duodenum in Dogs with Inflammatory Bowel Disease

Background: Endoscopy is performed for direct inspection of the mucosa and acquisition of biopsies in dogs with inflammatory bowel disease (IBD). Aim: To evaluate the interobserver agreement in the endoscopic assessment of duodenal mucosa in dogs with IBD. Methods: Thirty-five archived endoscopic images of grossly normal (n = 6) and inflamed (n = 29) duodenal mucosa were displayed to 3 expert and 5 trainee endoscopists. Each image was assessed independently by endoscopists for mucosal abnormalities using established indices (of hyperemia, granularity, friability, lymphatic dilatation, and erosions) or interpreted as normal mucosa (trial 1). A repeated trial (trial 2) was performed with the same images presented in random order 1 month later, and accompanied by a visual template. Results: There was slight interobserver agreement in initial mucosal assessment for expert and trainee endoscopists in trial 1 (kappa ≤ 0.02, P \u3e .05). Interobserver agreement improved in trial 2 for both expert and trainee endoscopists (kappa = 0.2, P \u3e .05) for experts and (P \u3c .05) for trainees. There was a significant (P \u3c .01) improvement in trainee endoscopy scores of lesions from trial 1 to trial 2. Regression analysis showed a significant (P \u3c .01) difference between expert versus trainee endoscopy scores in trial 1. Repeat lesion assessment aided by use of a visual template (trial 2) improved the overall scores of trainee endoscopists to near that of expert endoscopists (P = .06). Conclusions and Clinical Importance: Interobserver agreement of IBD mucosal appearance from endoscopic findings benefitted from operator experience

Comparison of Molecular Phenotypes of Ductal Carcinoma In Situ and Invasive Breast Cancer

Introduction: At least four major categories of invasive breast cancer that are associated with different clinical outcomes have been identified by gene expression profiling: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) and basal-like. However, the prevalence of these phenotypes among cases of ductal carcinoma in situ (DCIS) has not been previously evaluated in detail. The purpose of this study was to compare the prevalence of these distinct molecular subtypes among cases of DCIS and invasive breast cancer. Methods: We constructed tissue microarrays (TMAs) from breast cancers that developed in 2897 women enrolled in the Nurses' Health Study (1976 to 1996). TMA slides were immunostained for oestrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR). Using these immunostain results, cases were grouped into molecularly defined subtypes. Results: The prevalence of the distinct molecular phenotypes differed significantly between DCIS (n = 272) and invasive breast cancers (n = 2249). The luminal A phenotype was significantly more frequent among invasive cancers (73.4%) than among DCIS lesions (62.5%) (p = 0.0002). In contrast, luminal B and HER2 molecular phenotypes were both more frequent among DCIS (13.2% and 13.6%, respectively) as compared with invasive tumours (5.2% and 5.7%, respectively) (p < 0.0001). The basal-like phenotype was more frequent among the invasive cancers (10.9%) than DCIS (7.7%), although this difference was not statistically significant (p = 0.15). High-grade DCIS and invasive tumours were more likely to be HER2 type and basal-like than low- or intermediate-grade lesions. Among invasive tumours, basal-like and HER2 type tumours were more likely to be more than 2 cm in size, high-grade and have nodal involvement compared with luminal A tumours. Conclusion: The major molecular phenotypes previously identified among invasive breast cancers were also identified among cases of DCIS. However, the prevalence of the luminal A, luminal B and HER2 phenotypes differed significantly between DCIS and invasive breast cancers