Leading the Play: Development of a Method Supporting Expression and Control with Adults with Dementia

This paper explores the concept of client-led play with older adults with dementia and its possible impact on an individual’s ability to express enjoyment and sense of control. Expressive arts therapy is explored as a possible natural vehicle for providing client-led play groups to older adults with dementia. While research is limited regarding client-led play specifically, there has been significant research supporting the use of the creative arts with individuals with dementia, as it provides opportunities for non-verbal expression and spontaneous creativity. This paper argues that the arts have a natural connection to play through the use of the imagination and in-the-moment choice making. The author developed and implemented two play-based interventions with adults with dementia at an assisted living facility in Massachusetts. This paper will discuss the literature that informed the method, what took place during the implementation, and what was learned from observing and experiencing client-led play with adults with dementia

Emotion regulation among adults with asthma: Links with short-acting inhaler medication overuse and utilization of acute medical care

Effective control of asthma symptoms requires daily self-management activities, including use of short-acting or “rescue” inhaled medications. Overuse of short-acting inhaled medications, such as albuterol, can have negative side-effects, including respiratory infections and worse asthma symptom control. Existing research suggests that emotion plays an important role in airway inflammation and asthma symptom control. The objective of this study was to determine whether difficulties regulating emotion was associated with overuse of short-acting inhaled medications and acute medical care usage in adults with asthma. The sample included 401 adults with asthma recruited from an online panel of adults with chronic respiratory disease. Respondents completed a survey that included measures of short-acting medication use, acute medical service use, and emotion regulation (Difficulties in Emotion Regulation Scale [DERS]). Sequential binary logistic regression models were used to examine the association between DERS scores with two indicators of short-acting inhaled medication overuse: using \u3e3 canisters of short-acting inhaled medications in the past three months or self-reported overuse (i.e., using short-acting inhaled medications more than prescribed) while controlling for patient characteristics (current smoking and health insurance status) and comorbid mental health conditions (probable depression and probable anxiety). The results showed that greater difficulties in emotion regulation was significantly associated with greater odds of using more than three canisters in the past three months (AOR = 1.023, 95%CI [1.012, 1.035], p \u3c .001) and using short-acting inhaled medications more than prescribed (AOR = 1.024, 95%CI [1.014, 1.035], p \u3c .001) as well as with greater odds of emergency department visits (AOR = 1.018, 95%CI [1.009, 1.028], p AOR = 1.017, 95%CI [1.007, 1.028], p=.001) in the prior 12-months – even after adjusting for probable depression and probable anxiety, current smoking, and health insurance status. In conclusion, emotion dysregulation may play an important role in overuse of short-acting inhaled medications and acute medical care utilization among adults with asthma. Evidence-based interventions to reduce difficulties in emotion regulation may help improve problematic patterns of short-acting medication overuse among adults with asthma

Frequency over function : raised levels of CD127low/- regulatory T cells in the tumour microenvironment compared with the periphery of head and neck cancer patients

Objective: Regulatory T cells (Tregs) are known to infiltrate the tumour microenvironment of many cancers, including head and neck malignancies, and are thought to contribute to the host's impaired anti-tumour immune response. However, their immunosuppressive function remains poorly understood within the tumour microenvironment and this study aimed to address this. Methods: The frequency and suppressive capacity of two CD4?CD127low/- Treg populations, separated on the basis of different levels of CD25 expression (CD25inter and CD25high), from the tumour/node microenvironment and peripheral circulation of newly-presenting head and neck squamous cell carcinoma patients (n=19), were assessed using multicolour flow cytometry. Results: The proportion of Tregs (CD4?CD25high/?interCD127low/-) in the tumour/node microenvironment was significantly elevated compared with the peripheral circulation (p<0.001) and similar percentages were present in both the primary tumour and metastatic lymph node. The percentage of suppression induced by Tregs isolated from tumour associated nodes on the proliferation of nodal effector T cells was similar to that of peripheral Tregs on peripheral effector T cells. However, when the suppressive activity of both nodal and peripheral Tregs was compared on the same peripheral effectors, peripheral Tregs suppressed proliferation to a greater extent. Conclusion: This work shows that the recruitment and percentages of tumour infiltrating Tregs are key factors in modulating the immune environment of head and neck tumours

The Critical Middle Years and the Relationship of Early Access to Algebra on High School Math Course Completion and College Readiness

Many students who enroll in higher education are unprepared to meet the challenges of postsecondary education. The probability that students will make a successful transition from high school to college is linked to the degree to which their secondary educational experiences have prepared them for the expectations and demands they will encounter in college. National findings provide continuing evidence that focusing on improving student achievement in mathematics will positively impact college readiness. The main problem addressed in this quantitative study was how educators can best prepare students for college readiness. Since college readiness is highly dependent upon math achievement in middle schools, postsecondary educators need additional research that explores how math curricula may ultimately impact the readiness of their college students. Therefore, seemingly benign decisions about placement of students in middle school math may ultimately impact greatly on their college readiness. In addition, the study focused on the implications of those placement decisions. Chi-square Automatic Interaction Detection (CHAID) was used to determine those variables that were most significantly associated with students\u27 math-related college readiness as evidenced by advanced mathematics coursework taken beyond Algebra I

Measuring the response of human head and neck squamous cell carcinoma to irradiation in a microfluidic model allowing customized therapy

Radiotherapy is the standard treatment for head and neck squamous cell carcinoma (HNSCC), however, radioresistance remains a major clinical problem despite significant improvements in treatment protocols. Therapeutic outcome could potentially be improved if a patient's tumour response to irradiation could be predicted ex vivo before clinical application. The present study employed a bespoke microfluidic device to maintain HNSCC tissue whilst subjecting it to external beam irradiation and measured the responses using a panel of cell death and proliferation markers. HNSCC biopsies from five newly-presenting patients [2 lymph node (LN); 3 primary tumour (PT)] were divided into parallel microfluidic devices and replicates of each tumour were subjected to single-dose irradiation (0, 5, 10, 15 and 20 Gy). Lactate dehydrogenase (LDH) release was measured and tissue sections were stained for cytokeratin (CK), cleaved-CK18 (cCK18), phosphorylated-H2AX (λH2AX) and Ki.67 by immunohistochemistry. In addition, fragmented DNA was detected using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Compared with non.irradiated controls, higher irradiation doses resulted in elevated CK18-labelling index in two lymph nodes [15 Gy; 34.8% on LN1 and 31.7% on LN2 (p=0.006)] and a single laryngeal primary tumour (20 Gy; 31.5%; p=0.014). Significantly higher levels of DNA fragmentation were also detected in both lymph node samples and one primary tumour but at varying doses of irradiation, i.e., LN1 (20 Gy; 27.6%; p=0.047), LN2 (15 Gy; 15.3%; p=0.038) and PT3 (10 Gy; 35.2%; p=0.01). The λH2AX expression was raised but not significantly in the majority of samples. The percentage of Ki.67 positive nuclei reduced dose-dependently following irradiation. In contrast no significant difference in LDH release was observed between irradiated groups and controls. There is clear interand intra-patient variability in response to irradiation when measuring a variety of parameters, which offers the potential for the approach to provide clinically valuable information

Prelicensure Nursing Students’ Perceptions of a Rapid Transition to an Online Learning Environment

The transition to a fully online environment after the spread of the COVID-19 pandemic left all educators with the need to quickly transition didactic classes to the online environment and attempt to understand and utilize online teaching modalities. Online learning has only recently become integrated into nursing education, creating a gap in literature in relation to the most appropriate strategies for online course delivery, specifically in prelicensure nursing. This chapter explores the background to the project, types of learning environments, definitions of terms utilized, and purpose of the secondary analysis

Maintenance of head and neck tumor on-chip: gateway to personalized treatment?

Aim: Head and neck squamous cell carcinomas (HNSCC) are solid tumors with low overall survival (40–60%). In a move toward personalized medicine, maintenance of tumor biopsies in microfluidic tissue culture devices is being developed. Methodology/ results: HNSCC (n = 15) was dissected (5–10 mg) and either analyzed immediately or cultured in a microfluidic device (37°C) for 48 h. No difference was observed in morphology between pre- and postculture specimens. Dissociated samples were analyzed using trypan blue exclusion (viability), propidium iodide flow cytometry (death) and MTS assay (proliferation) with no significant difference observed highlighting tissue maintenance. Computational fluid dynamics showed laminar flow within the system. Conclusion: The microfluidic culture system successfully maintained HNSCC for 48 h, the culture system will allow testing of different treatment modalities with response monitoring. Lay abstract: Head and neck cancers often have a poor treatment outcome. In order to study the response of the tissue, a miniaturized culture system has been developed to keep a small piece of tumor alive. In the current study, we show that small pieces of cancer tissue can be maintained in the system, using tissue structure and viability of single cells as a guide. In future work, patient equivalent treatments can be applied to these microculture systems to investigate individual patient tumor responses, which could help to guide treatment selection

Inhibition of Human Immunodeficiency virus replication through small RNA-induced gene silencing of HIV-1 Tat specific factor 1

Ph.D., Faculty of Health Sciences, University of the Witwatersrand, 2011The HIV-­‐1 pandemic continues unabated. Although treatments exist that can substantially alleviate the morbidity and mortality associated with HIV, there is still a need for improved anti-­‐HIV treatments that reduce toxicities and administration frequency and mediate sustained inhibition of viral replication. Given the high mutability and variability of the virus, a strategy that is garnering increasing focus is the targeting of host factors that the virus requires to replicate, so-­‐called HIV-­‐dependency factors (HDFs). It is hoped this will reduce the emergence of viral drug resistance. A number of genome-­‐wide screens have been performed to identify HDFs, although many remain to be validated, particularly in relevant cells lines. An objective of this thesis was to validate three host factors as HDFs, in both TZM-­‐bl reporter and T cell-­‐derived cell lines, and to examine their potential as anti-­‐HIV-­‐1 therapeutic targets through exploitation of the cellular gene silencing pathway, RNA interference (RNAi). These were HIV-­‐1 Tat specific factor 1 (HTATSF1), DEAD (Asp-­‐Glu-­‐Ala-­‐Asp) box polypeptide 3, X-­‐ linked (DDX3X) and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1 (SMARCB1), selected because they had been previously implicated in HIV-­‐ 1 pathogenesis. The well-­‐characterised HDF, PC4 and SFRS1 interacting protein 1 (PSIP1)/lens epithelium-­‐derived growth factor (LEDGF)/p75, was included in the study as a positive control. Cassettes expressing short hairpin RNAs (shRNAs) targeting the four host proteins were generated, although shRNAs did not suppress endogenous ddx3x mRNA levels. The ability of shRNAs to inhibit HIV-­‐1 replication in the reporter cell line, TZM-­‐bl, was examined. These HeLa-­‐ derived cells are permissive for R5-­‐tropic HIV-­‐1 infection and contain an integrated luciferase gene driven by the viral promoter. shRNAs mediated a dose-­‐dependent inhibition of luciferase activity in cells infected with a HIV-­‐1 subtype B molecular clone and, although production of the viral protein p24 was unaltered, infectious particle production was decreased in cells treated with a shRNA suppressing HTATSF1. Little effect was observed with a shRNA targeting SMARCB1, suggesting that this may not function as an HDF under these conditions. No effect on infectious particle production was seen with the shRNA targeting PSIP1, which was a result of the long half-­‐ life of this protein, highlighting a limitation of using such reporter systems for HDF validation. Importantly, shRNAs were not associated with any cytotoxic effects in TZM-­‐bl cells. Whether HTATSF1 is a potential therapeutic target was interrogated further in the more relevant T cell-­‐derived SupT1 cell line. Lentiviruses were used to generate populations where >90% had one copy of the integrated shRNA expression cassette. Replication of the subtype B molecular clone p81A-­‐4 was significantly inhibited in the shH1-­‐expressing SupT1 cell line, which targets HTATSF1, for over 14 days post-­‐infection, although inhibition was not as pronounced asthat observed in the shP1-­‐expressing SupT1 cell line, which targets PSIP1. In contrast to a previous report, no change in the ratio of unspliced to singly-­‐ or multiply-­‐spliced HIV-­‐1 transcripts were detected in shH1-­‐expressing SupT1 cells, suggesting that HTATSF1 does not function as a splicing cofactor in this system. A slight rebound in p24 levels at 14 days post-­‐infection was accompanied by increased HTATSF1 expression and a decrease in the percentage of cells with transgene expression in the population. In addition, there was a slight decrease in shH1-­‐derived guide strand expression, but no change in transcription rates of the htatsf1 gene, suggesting that cells within the population with shH1 expression and HTATSF1 suppression may have a growth disadvantage. Thus, although this work demonstrates for the first time that HTATSF1 functions as an HDF in T cell-­‐derived SupT1 cells, it may not constitute a viable therapeutic target. A second objective of this thesis was to examine the feasibility of transcriptional gene silencing (TGS) of HDFs as an anti-­‐HIV strategy. TGS is a small RNA-­‐induced gene silencing pathway that operates through chromatin remodelling with the potential to mediate long-­‐term silencing of gene expression. Thus, its application may reduce the frequency of drug administration and associated toxicities. Short interfering RNAs (siRNAs) targeting the htatsf1 promoter were able to reduce target mRNA expression, which was accompanied by decreased htatsf1 transcription rates in HEK293T cells, suggesting silencing via a TGS mechanism. The htatsf1 silencing inhibited infectious HIV-­‐1 particle production from TZM-­‐bl cells. This work provides proof of principle that TGS induction at a HDF may inhibit HIV-­‐1 replication. siRNAs targeting the ddx3x promoter did not induce TGS. To examine whether gene susceptibility to TGS may be influenced by promoter architectures, 49 promoter features were examined for enrichment in genes at which small RNA-­‐induced TGS has been reported. Initially, the TGS group was compared to a random set of 2,000 promoters and then all other promoters in the genome. To control for gene activation, two further analyses were performed comparing the TGS group features to those from promoters active in the THP-­‐1 cell line and housekeeping genes. Whilst difficult to ascribe differences between the TGS group and the control groups to anything beyond a variation in the proportion of active genes within each group, there was enrichment for certain promoter features that are independent of activity; the TGS group was characterised by broad transcription start regions, high CpG content and a single expression profile. Moreover, the fraction of promoters with reported non-­‐coding RNA overlap was greater in the TGS group than the control groups. Thus, there is some evidence that a number of promoter features are associated with TGS susceptibility. It is hoped this novel analysis will facilitate selection of future TGS targets, including HDFs. In summary, the work presented in this thesis paves the way for development of improved anti-­‐HIV therapies involving HDF-­‐targeted TGS-­‐based gene therapies that mediate sustained inhibition of the virus

The Role of Chemokines in Thyroid Carcinoma

© Copyright 2017, Mary Ann Liebert, Inc. 2017. The global incidence of thyroid cancer is increasing, and metastatic spread to the lymph nodes is common in papillary thyroid carcinoma. The metastatic course of thyroid carcinoma is an intricate process involving invasion, angiogenesis, cell trafficking, extravasation, organ specific homing, and growth. A key aspect in this process involves a multitude of interactions between chemokines and their receptors. Chemokines are a group of small proteins, which act to elicit normal physiologic and immune responses principally through recruitment of specific cell populations to the site of infection or malignancy. Thyroid cancer cells, like other tumors, possess the ability to corrupt the chemokine system to their advantage by altering cell movement into the tumor microenvironment and affecting all aspects of thyroid cancer progression