Activity Strategy Workbook for Mothers Experiencing Multiple Sclerosis

The purpose of this scholarly project was to create a resource for mothers diagnosed with multiple sclerosis (MS) to promote optimal success and independence in the motherhood role. The resulting workbook targets the mothering activities of individuals who have been newly diagnosed with MS and are raising young, pre-school aged children. The product provides education and guidance to optimize the mother\u27s ability to care for herself and her child or children. A comprehensive literature review was conducted to examine current best practice and treatment guidelines for MS, the influence of MS on both the parent and child, and also common symptoms and their effects on occupational functioning. The literature revealed a common underuse of energy promotion during the treatment of MS and an overemphasis on energy conservation strategies. Research also demonstrated a correlation between the mother\u27s symptom level and her ability to provide care and nurturing to her child. Specific focus was therefore placed on adapting mothering activities to balance energy conservation and energy promotion techniques according to fatigue fluctuations and symptom exacerbation. Emphasis was given to providing mothers with the opportunity to gain insight into the effectiveness of strategies used to carry out self-care, household management, and childcare activities. Guided by the Occupational Adaptation (OA) Model, the workbook promotes occupational mastery and skill generalization and is intended to be used as a supplement to occupational therapy (OT) services

Study Away with SFA: The Opportunity for Accessible Cross Cultural Learning

Study Away was proposed by our professor as an accessible alternative to traditional study abroad programs. Accessible because it is more affordable and it opens up this cross cultural opportunity to students who may be undocumented. We traveled the country for five weeks in a Mercedes sprinter van exploring places such as Palo Duro Canyon State Park, Albuquerque, the Great Lakes, New York City, the Appalachian Mountains, and New Orleans to name a few. Throughout, we engaged in critical conversations and opportunities for self-growth. This presentation will share our perspectives regarding study away as it compares to study abroad

Walt Disney Concert Hall

The Walt Disney Concert Hall in Los Angeles, California is an iconic building well known and loved by the public, but at one time the project was considered insurmountable. The Concert hall itself is only one part of the overall experience of the building. Set on top of a spacious and inconspicuous parking garage, the structure itself displays a distinctive image composed of stainless steel, plaster, glass, and concrete. The concept for such a building started in 1987 when Lilian Disney gave a 50-million-dollar donation to the city of Los Angeles. An architect named Frank Gehry provided the design we can see today. Construction was moving smoothly until 1994 when funding issues arose, and the process was brought to a halt. The city considered pulling the project until local philanthropists began to donate in a frenzy, raising approximately 274 million dollars in total. Throughout the construction process there were obstacles that are common with structures of this caliber, but they were successfully overcome to complete the project on October 23rd, 2003. Still today, the outstanding acoustical balance, subtle cues, material use and are considered to be some of the best in the world

Elevated levels of extracellular vesicles in progranulin-deficient mice and FTD-GRN Patients.

ObjectiveThe goal of this study was to investigate the effect of progranulin insufficiency on extracellular vesicles (EVs), a heterogeneous population of vesicles that may contribute to progression of neurodegenerative disease. Loss-of-function mutations in progranulin (GRN) are a major cause of frontotemporal dementia (FTD), and brains from GRN carriers with FTD (FTD-GRN) exhibit signs of lysosomal dysfunction. Lysosomal dysfunction may induce compensatory increases in secretion of exosomes, EVs secreted from the endolysosomal system, so we hypothesized that progranulin insufficiency would increase EV levels in the brain.MethodsWe analyzed levels and protein contents of brain EVs from Grn-/- mice, which model the lysosomal abnormalities of FTD-GRN patients. We then measured brain EVs in FTD-GRN patients. To assess the relationship of EVs with symptomatic disease, we measured plasma EVs in presymptomatic and symptomatic GRN mutation carriers.ResultsGrn-/- mice had elevated brain EV levels and altered EV protein contents relative to wild-type mice. These changes were age-dependent, occurring only after the emergence of pathology in Grn-/- mice. FTD-GRN patients (n = 13) had elevated brain EV levels relative to controls (n = 5). Symptomatic (n = 12), but not presymptomatic (n = 7), GRN carriers had elevated plasma EV levels relative to controls (n = 8).InterpretationThese data show that symptomatic FTD-GRN patients have elevated levels of brain and plasma EVs, and that this effect is modeled in the brain of Grn-/- mice after the onset of pathology. This increase in EVs could influence FTD disease progression, and provides further support for EVs as potential FTD biomarkers

Patients with sporadic FTLD exhibit similar increases in lysosomal proteins and storage material as patients with FTD due to GRN mutations.

Loss of function progranulin (GRN) mutations are a major autosomal dominant cause of frontotemporal dementia (FTD). Patients with FTD due to GRN mutations (FTD-GRN) develop frontotemporal lobar degeneration with TDP-43 pathology type A (FTLD-TDP type A) and exhibit elevated levels of lysosomal proteins and storage material in frontal cortex, perhaps indicating lysosomal dysfunction as a mechanism of disease. To investigate whether patients with sporadic FTLD exhibit similar signs of lysosomal dysfunction, we compared lysosomal protein levels, transcript levels, and storage material in patients with FTD-GRN or sporadic FTLD-TDP type A. We analyzed samples from frontal cortex, a degenerated brain region, and occipital cortex, a relatively spared brain region. In frontal cortex, patients with sporadic FTLD-TDP type A exhibited similar increases in lysosomal protein levels, transcript levels, and storage material as patients with FTD-GRN. In occipital cortex of both patient groups, most lysosomal measures did not differ from controls. Frontal cortex from a transgenic mouse model of TDP-opathy had similar increases in cathepsin D and lysosomal storage material, showing that TDP-opathy and neurodegeneration can drive these changes independently of progranulin. To investigate these changes in additional FTLD subtypes, we analyzed frontal cortical samples from patients with sporadic FTLD-TDP type C or Pick's disease, an FTLD-tau subtype. All sporadic FTLD groups had similar increases in cathepsin D activity, lysosomal membrane proteins, and storage material as FTD-GRN patients. However, patients with FTLD-TDP type C or Pick's disease did not have similar increases in lysosomal transcripts as patients with FTD-GRN or sporadic FTLD-TDP type A. Based on these data, accumulation of lysosomal proteins and storage material may be a common aspect of end-stage FTLD. However, the unique changes in gene expression in patients with FTD-GRN or sporadic FTLD-TDP type A may indicate distinct underlying lysosomal changes among FTLD subtypes

Patients with sporadic FTLD exhibit similar increases in lysosomal proteins and storage material as patients with FTD due to GRN mutations

Abstract Loss of function progranulin (GRN) mutations are a major autosomal dominant cause of frontotemporal dementia (FTD). Patients with FTD due to GRN mutations (FTD-GRN) develop frontotemporal lobar degeneration with TDP-43 pathology type A (FTLD-TDP type A) and exhibit elevated levels of lysosomal proteins and storage material in frontal cortex, perhaps indicating lysosomal dysfunction as a mechanism of disease. To investigate whether patients with sporadic FTLD exhibit similar signs of lysosomal dysfunction, we compared lysosomal protein levels, transcript levels, and storage material in patients with FTD-GRN or sporadic FTLD-TDP type A. We analyzed samples from frontal cortex, a degenerated brain region, and occipital cortex, a relatively spared brain region. In frontal cortex, patients with sporadic FTLD-TDP type A exhibited similar increases in lysosomal protein levels, transcript levels, and storage material as patients with FTD-GRN. In occipital cortex of both patient groups, most lysosomal measures did not differ from controls. Frontal cortex from a transgenic mouse model of TDP-opathy had similar increases in cathepsin D and lysosomal storage material, showing that TDP-opathy and neurodegeneration can drive these changes independently of progranulin. To investigate these changes in additional FTLD subtypes, we analyzed frontal cortical samples from patients with sporadic FTLD-TDP type C or Pick’s disease, an FTLD-tau subtype. All sporadic FTLD groups had similar increases in cathepsin D activity, lysosomal membrane proteins, and storage material as FTD-GRN patients. However, patients with FTLD-TDP type C or Pick’s disease did not have similar increases in lysosomal transcripts as patients with FTD-GRN or sporadic FTLD-TDP type A. Based on these data, accumulation of lysosomal proteins and storage material may be a common aspect of end-stage FTLD. However, the unique changes in gene expression in patients with FTD-GRN or sporadic FTLD-TDP type A may indicate distinct underlying lysosomal changes among FTLD subtypes

B cell‐dependent subtypes and treatment‐based immune correlates to survival in stage 3 and 4 lung adenocarcinomas

Abstract Lung cancer is the leading cause of cancer‐related deaths worldwide. Surgery and chemoradiation are the standard of care in early stages of non‐small cell lung cancer (NSCLC), while immunotherapy is the standard of care in late‐stage NSCLC. The immune composition of the tumor microenvironment (TME) is recognized as an indicator for responsiveness to immunotherapy, although much remains unknown about its role in responsiveness to surgery or chemoradiation. In this pilot study, we characterized the NSCLC TME using mass cytometry (CyTOF) and bulk RNA sequencing (RNA‐Seq) with deconvolution of RNA‐Seq being performed by Kassandra, a recently published deconvolution tool. Stratification of patients based on the intratumoral abundance of B cells identified that the B‐cell rich patient group had increased expression of CXCL13 and greater abundance of PD1+ CD8 T cells. The presence of B cells and PD1+ CD8 T cells correlated positively with the presence of intratumoral tertiary lymphoid structures (TLS). We then assessed the predictive and prognostic utility of these cell types and TLS within publicly available stage 3 and 4 lung adenocarcinoma (LUAD) RNA‐Seq datasets. As previously described by others, pre‐treatment expression of intratumoral 12‐chemokine TLS gene signature is associated with progression free survival (PFS) in patients who receive treatment with immune checkpoint inhibitors (ICI). Notably and unexpectedly pre‐treatment percentages of intratumoral B cells are associated with PFS in patients who receive surgery, chemotherapy, or radiation. Further studies to confirm these findings would allow for more effective patient selection for both ICI and non‐ICI treatments