Faculty-Led Virtual Level 1 Community Fieldwork during the COVID-19 Pandemic

Fieldwork is an integral portion of occupational therapy education that ensures students have the opportunity to develop basic competencies in real world practice settings. The national shortage of fieldwork placements, particularly in the area of mental health, in combination with the COVID-19 pandemic, have led to the adoption of increasingly innovative fieldwork models. This retrospective, qualitative study investigates occupational therapy assistant students’ experiences of completing a faculty-led (i.e. where faculty served as the primary fieldwork educator) and virtual (i.e., where services were offered in a virtual environment) Level I fieldwork with a community-based peer led behavioral health agency. Twenty-three students completed a confidential survey describing their experiences in Fall 2020. A secondary analysis of students’ responses was performed using principles of thematic analysis, which yielded results centered on four themes: knowledge, skills, attitudes, and structure. Subcategories highlighted growth across multiple areas including knowledge of occupational therapy’s role in mental health, interpersonal skills, and use of technology and other resources. Students’ preconceived notions of individuals with mental illness were challenged and many reported increased confidence in their abilities to work with these individuals. Both positive and constructive feedback were provided regarding the overall virtual fieldwork experience. The faculty-led virtual fieldwork model was viable in supporting occupational therapy assistant students’ skills to engage people with mental health and substance use challenges in a community setting. The potential use of this model is discussed in light of the anticipated increase of behavioral health problems for many across the lifespan post-COVID-19 pandemic

Sequences of Regressions Distinguish Nonmechanical from Mechanical Associations between Metabolic Factors, Body Composition, and Bone in Healthy Postmenopausal Women

Background: There is increasing recognition of complex interrelations between the endocrine functions of bone and fat tissues or organs.  Objective: The objective was to describe nonmechanical and mechanical links between metabolic factors, body composition, and bone with the use of graphical Markov models.  Methods: Seventy postmenopausal women with a mean ± SD age of 62.3 ± 3.7 y and body mass index (in kg/m2) of 24.9 ± 3.8 were recruited. Bone outcomes were peripheral quantitative computed tomography measures of the distal and diaphyseal tibia, cross-sectional area (CSA), volumetric bone mineral density (vBMD), and cortical CSA. Biomarkers of osteoblast and adipocyte function were plasma concentrations of leptin, adiponectin, osteocalcin, undercarboxylated osteocalcin (UCOC), and phylloquinone. Body composition measurements were lean and percent fat mass, which were derived with the use of a 4-compartment model. Sequences of Regressions, a subclass of graphical Markov models, were used to describe the direct (nonmechanical) and indirect (mechanical) interrelations between metabolic factors and bone by simultaneously modeling multiple bone outcomes and their relation with biomarker outcomes with lean mass, percent fat mass, and height as intermediate explanatory variables.  Results: The graphical Markov models showed both direct and indirect associations linking plasma leptin and adiponectin concentrations with CSA and vBMD. At the distal tibia, lean mass, height, and adiponectin-UCOC interaction were directly explanatory of CSA (R2 = 0.45); at the diaphysis, lean mass, percent fat mass, leptin, osteocalcin, and age-adiponectin interaction were directly explanatory of CSA (R2 = 0.49). The regression models exploring direct associations for vBMD were much weaker, with R2 = 0.15 and 0.18 at the distal and diaphyseal sites, respectively. Lean mass and UCOC were associated, and the global Markov property of the graph indicated that this association was explained by osteocalcin.  Conclusions: This study, to our knowledge, offers a novel approach to the description of the complex physiological interrelations between adiponectin, leptin, and osteocalcin and the musculoskeletal system. There may be benefits to jointly targeting both systems to improve bone health

Telomerase Inhibition Targets Clonogenic Multiple Myeloma Cells through Telomere Length-Dependent and Independent Mechanisms

Plasma cells constitute the majority of tumor cells in multiple myeloma (MM) but lack the potential for sustained clonogenic growth. In contrast, clonotypic B cells can engraft and recapitulate disease in immunodeficient mice suggesting they serve as the MM cancer stem cell (CSC). These tumor initiating B cells also share functional features with normal stem cells such as drug resistance and self-renewal potential. Therefore, the cellular processes that regulate normal stem cells may serve as therapeutic targets in MM. Telomerase activity is required for the maintenance of normal adult stem cells, and we examined the activity of the telomerase inhibitor imetelstat against MM CSC. Moreover, we carried out both long and short-term inhibition studies to examine telomere length-dependent and independent activities.Human MM CSC were isolated from cell lines and primary clinical specimens and treated with imetelstat, a specific inhibitor of the reverse transcriptase activity of telomerase. Two weeks of exposure to imetelstat resulted in a significant reduction in telomere length and the inhibition of clonogenic MM growth both in vitro and in vivo. In addition to these relatively long-term effects, 72 hours of imetelstat treatment inhibited clonogenic growth that was associated with MM CSC differentiation based on expression of the plasma cell antigen CD138 and the stem cell marker aldehyde dehydrogenase. Short-term treatment of MM CSC also decreased the expression of genes typically expressed by stem cells (OCT3/4, SOX2, NANOG, and BMI1) as revealed by quantitative real-time PCR.Telomerase activity regulates the clonogenic growth of MM CSC. Moreover, reductions in MM growth following both long and short-term telomerase inhibition suggest that it impacts CSC through telomere length-dependent and independent mechanisms

Development and validation of a targeted gene sequencing panel for application to disparate cancers.

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour's molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy

The 'demented other' or simply 'a person'? Extending the philosophical discourse of Naue and Kroll through the situated self

This article presents a critique of an article previously featured in Nursing Philosophy (10: 26-33) by Ursula Naue and Thilo Kroll, who suggested that people living with dementia are assigned a negative status upon receipt of a diagnosis, holding the identity of the 'demented other'. Specifically, in this critique, we suggest that unwitting use of the adjective 'demented' to define a person living with the condition is ill-informed and runs a risk of defining people through negative (self-)attributes, which has a deleterious impact upon that person's social and relational personae. Moreover, use of the locution 'demented' reinforces a divide between the 'demented' (them) and the 'healthy others' (us). Social constructionist theory, malignant positioning and viewing people with dementia as semiotic subjects are the philosophical pillars through which we construct the main arguments of the critique. The article concludes with the voice of one of the authors, a younger person with dementia, asking for language in dementia care to be carefully reconsidered and reframed and for the recognition of the diagnosed person's agency in the conduct of their day-to-day lives. © 2011 Blackwell Publishing Ltd

NS3 helicase from dengue virus specifically recognizes viral RNA sequence to ensure optimal replication.

10.1093/nar/gkx1127Nucleic Acids Research452212904-1292