INCREASING PARENT CONFIDENCE AND INVOLVEMENT IN THE NICU: AN OCCUPATIONAL THERAPY EDUCATIONAL GUIDE

Research shows that 40% of mothers with preterm infants in the neonatal intensive care unit (NICU) reported feelings of depression, and 23% reported experiencing post-traumatic stress symptoms, with that number increasing to 40% after discharge (Harris et al., 2018). Factors that contributed to this included a lack of social support, a lack of empowerment, perceived less capability in their new roles, and the stressful experiences that can happen in this setting (Matricardi et al., 2013; Sabnis et al., 2019). A similar study found that at discharge, 69.8% of parents reported that they were not confident in providing the necessary care to their infant without the support of the NICU providers and 47.2% reported that their infant required complex home care post-discharge. Parents also reported that returning to their daily routine took roughly 4 to 11 months post-discharge (Jiménez-Palomares et al., 2021). Occupational therapy has a significant role in this setting by facilitating parents’ involvement in their care while also increasing their confidence to continue care at discharge (Harris et al., 2018; Reynolds et al., 2013)

Identifying Occupational Therapy’s Role in the Interprofessional Team for Combating Barriers to Correct Medication Adherence for Older Adults

Occupational therapy is crucial to the interprofessional team, with a focus on client-centered interventions, a holistic approach to health promotion and prevention and a comprehensive overlook on quality of life. The focus of occupational therapy is to collaborate with clients to find meaningful engagement in occupations to promote participation. The occupational therapist’s perspective on the person holistically marks their contribution to the interprofessional team in order to meet the needs to provide for the client, their families, and their community (Doll & Earland, 2020). Other than occupational therapists, the interdisciplinary team may consist of nurses, pharmacists and caregivers. Nurses are in a position to teach medication self-management to patients and their families to prepare them for discharge. Pharmacists are in a position where they are able to review regimen complexity when conducting medication reviews (Elliot, et al., 2013). In addition, they directly communicate information to the patient\u27s primary healthcare provider. By doing so, the patient will have a clearer understanding of the appropriate medications to consume. Formal and informal caregivers, who are taught to distribute medications properly to those they are caring for, can be seen as collaborators in the interdisciplinary team

О методах расчета ?'-потенциала при наличии адсорбированных на электроде органических веществ

Проведено сравнение исходных посылок различных методов расчета ?'-потенциала и результатов расчета по этим методам для случая адсорбции на ртути ?-нафтола. Показано, что для адсорбирующихся веществ, меняющих ориентацию молекул относительно поверхности электрода лучшие результаты дает определение ?'-потенциала по сдвигу максимума электрокапиллярной кривой

Application of Bioimage Informatics to Quantification of Focal Adhesions and Invadopodia

The development of the ability to fluorescently label functional proteins and visualize their subcellular localization using microscopy in living cells, has made it possible to study a wide range of single cell phenomena. To understand the results of imaging assays, cell biologists have used manual methods for determining the quantitative properties of the cellular structures visualized fluorescent microscopy. As the quantity and complexity of the images that can be collected using fluorescence microscopy has increased, a new subfield of Bioinformatics has developed, named Bioimage Informatics, which specializes in adapting and developing new methods to quantify the image sets resulting from biological assays. In this thesis, I describe the application and development of Bioimage Informatic methods to the analysis of Focal Adhesions and Invadopodia. Focal Adhesions are subcellular protein complexes, whose role include acting as the points of contact for cellular motility and sensing the outside environment. Focal Adhesions have traditionally been analyzed using manual methods, which has limited the number of Focal Adhesions that could be analyzed and the depth of properties that could be collected. I have developed a set of methods which can identify, track and quantify Focal Adhesion properties from live cell image sets. This Focal Adhesion analysis framework has been expanded to include spatial and global methods for describing Focal Adhesion morphology. I have also developed a system for quantifying Invadopodia properties. Invadopodia are subcellular protein complexes present in metastatic cancer cells, which actively degrade the extracellular matrix, allowing migration of cancer cells away from primary tumors. This analysis system has two parts, one which can follow single Invadopodia and assess their properties and a complementary component which assesses degradation behavior in cell populations.Doctor of Philosoph

The Dark Kinase Knowledgebase: An online compendium of knowledge and experimental results of understudied kinases

Kinases form the backbone of numerous cell signaling pathways, with their dysfunction similarly implicated in multiple pathologies. Further facilitated by their druggability, kinases are a major focus of therapeutic development efforts in diseases such as cancer, infectious disease and autoimmune disorders. While their importance is clear, the role or biological function of nearly one-third of kinases is largely unknown. Here, we describe a data resource, the Dark Kinase Knowledgebase (DKK; https://darkkinome.org), that is specifically focused on providing data and reagents for these understudied kinases to the broader research community. Supported through NIH\u27s Illuminating the Druggable Genome (IDG) Program, the DKK is focused on data and knowledge generation for 162 poorly studied or \u27dark\u27 kinases. Types of data provided through the DKK include parallel reaction monitoring (PRM) peptides for quantitative proteomics, protein interactions, NanoBRET reagents, and kinase-specific compounds. Higher-level data is similarly being generated and consolidated such as tissue gene expression profiles and, longer-term, functional relationships derived through perturbation studies. Associated web tools that help investigators interrogate both internal and external data are also provided through the site. As an evolving resource, the DKK seeks to continually support and enhance knowledge on these potentially high-impact druggable targets

Kinome inhibition states and multiomics data enable prediction of cell viability in diverse cancer types

Protein kinases play a vital role in a wide range of cellular processes, and compounds that inhibit kinase activity emerging as a primary focus for targeted therapy development, especially in cancer. Consequently, efforts to characterize the behavior of kinases in response to inhibitor treatment, as well as downstream cellular responses, have been performed at increasingly large scales. Previous work with smaller datasets have used baseline profiling of cell lines and limited kinome profiling data to attempt to predict small molecule effects on cell viability, but these efforts did not use multi-dose kinase profiles and achieved low accuracy with very limited external validation. This work focuses on two large-scale primary data types, kinase inhibitor profiles and gene expression, to predict the results of cell viability screening. We describe the process by which we combined these data sets, examined their properties in relation to cell viability and finally developed a set of computational models that achieve a reasonably high prediction accuracy (R2 of 0.78 and RMSE of 0.154). Using these models, we identified a set of kinases, several of which are understudied, that are strongly influential in the cell viability prediction models. In addition, we also tested to see if a wider range of multiomics data sets could improve the model results and found that proteomic kinase inhibitor profiles were the single most informative data type. Finally, we validated a small subset of the model predictions in several triple-negative and HER2 positive breast cancer cell lines demonstrating that the model performs well with compounds and cell lines that were not included in the training data set. Overall, this result demonstrates that generic knowledge of the kinome is predictive of very specific cell phenotypes, and has the potential to be integrated into targeted therapy development pipelines

Instantaneous inactivation of cofilin reveals its function of F-actin disassembly in lamellipodia

Chromophore-assisted laser inactivation (CALI) was developed to instantly and specifically inactivate cofilin in cells. Simultaneous CALI and live imaging revealed that the principal role of cofilin in lamellipodia at steady state is to break down F-actin, control filament turnover, and regulate the rate of retrograde flow in lamellipodia.Cofilin is a key regulator of the actin cytoskeleton. It can sever actin filaments, accelerate filament disassembly, act as a nucleation factor, recruit or antagonize other actin regulators, and control the pool of polymerization-competent actin monomers. In cells these actions have complex functional outputs. The timing and localization of cofilin activity are carefully regulated, and thus global, long-term perturbations may not be sufficient to probe its precise function. To better understand cofilin's spatiotemporal action in cells, we implemented chromophore-assisted laser inactivation (CALI) to instantly and specifically inactivate it. In addition to globally inhibiting actin turnover, CALI of cofilin generated several profound effects on the lamellipodia, including an increase of F-actin, a rearward expansion of the actin network, and a reduction in retrograde flow speed. These results support the hypothesis that the principal role of cofilin in lamellipodia at steady state is to break down F-actin, control filament turnover, and regulate the rate of retrograde flow

Automated analysis of invadopodia dynamics in live cells

Multiple cell types form specialized protein complexes that are used by the cell to actively degrade the surrounding extracellular matrix. These structures are called podosomes or invadopodia and collectively referred to as invadosomes. Due to their potential importance in both healthy physiology as well as in pathological conditions such as cancer, the characterization of these structures has been of increasing interest. Following early descriptions of invadopodia, assays were developed which labelled the matrix underneath metastatic cancer cells allowing for the assessment of invadopodia activity in motile cells. However, characterization of invadopodia using these methods has traditionally been done manually with time-consuming and potentially biased quantification methods, limiting the number of experiments and the quantity of data that can be analysed. We have developed a system to automate the segmentation, tracking and quantification of invadopodia in time-lapse fluorescence image sets at both the single invadopodia level and whole cell level. We rigorously tested the ability of the method to detect changes in invadopodia formation and dynamics through the use of well-characterized small molecule inhibitors, with known effects on invadopodia. Our results demonstrate the ability of this analysis method to quantify changes in invadopodia formation from live cell imaging data in a high throughput, automated manner

Directing Mesenchymal Stem Cells with Gold Nanowire Arrays

Controlling cell organization is still a major bottleneck in biointerface engineering when the material dimensions decrease to the nanoscale. Here, Au nanowire-patterned array platforms with multiscale design from the macroscale to the nanoscale are developed for studying human bone marrow-derived mesenchymal stem cell (hBM-MSC) response. When the angle of the Au nanowires on glass is increased from 0 degrees to 90 degrees, hBM-MSC arrangement exhibits a transition from a unidirectional distribution induced by a vector response to a bimodal polarization pattern. The degree of cell vector response and elongation decreases with increasing nanowire angles from 0 degrees to 90 degrees. Further, it is demonstrated that the specific cell adhesion and organization are dependent on the surface micro/nanotopography, which is greatly enhanced by introducing stem cell-material affinity differences. An ideal model and new insights into a deeper understanding of cell-nano-biointerface interactions are provided.</p