Browsing by Subject "barrier"
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Item Open Access Levels of Surgical Disease and Predictors of Barriers to Care in Rural India(2012) Hudson, Jessica LynnAn estimated 234.2 million major surgical procedures are performed annually worldwide, yet the wealthiest third of the world's population receives 73.6% while the world's poorest third receives only 3.5%. Approximately one-third of the global population has no access to basic surgical care. Knowing that large unmet surgical need in a community can lead to high morbidity and mortality in the population, the purpose of this novel study was to assess the level of surgical conditions in rural Gadchiroli, India as well as to conduct a quantitative assessment of the barriers to surgical care. In this retrospective, cross-sectional needs assessment, a study-specific survey was administered in a clinic-based setting. Of the 500 participants, 141 (28.2%) reported surgical conditions, for a total of 175 surgical cases, in the preceding two years. The conditions with the highest prevalence were hydrocele, anorectal processes, dysfunctional uterine bleeding, cataracts, appendicitis, and spondylosis with neurologic claudication. Assessment of the conditions by a healthcare provider occurred in 133 (76.6%) of the cases of which only 32 (24.1%) reported having undergone surgery during the two year period. Overall, in this population, the burden of surgical disease is higher than previously expected and while willingness to undergo surgery is high, the completion rate is quite low. Certain factors appear to predict difficulty in seeking or receiving surgical care, including lost wages (p=0.027), the amount of time that family members need to stay in the hospital to help (p=0.038), and time away from work (p=0.045). Targeting these factors is a first step towards addressing the unmet surgical needs in this rural community.
Item Open Access Novel Roles for Desmosomes in Cytoskeletal Organization(2011) Sumigray, Kaelyn DMicrotubules often adopt non-centrosomal arrays in differentiated tissues, where they are important for providing structure to the cell and maintaining polarity. Although the formation and organization of centrosomal arrays has been well-characterized, little is known about how microtubules form non-centrosomal arrays.
In the mouse epidermis, centrosomes in differentiated cells lose their microtubule-anchoring ability through the loss of proteins from the centrosome. Instead, microtubules are organized around the cell cortex. The cell-cell adhesion protein desmoplakin is required for this organization. Our model is that desmoplakin recruits microtubule-anchoring proteins like ninein to the desmosome, where they subsequently recruit and organize microtubules.
To test this model, we confirmed that the microtubule-binding proteins Lis1, Ndel1, and CLIP170 are recruited by desmoplakin to the cell cortex. Furthermore, by creating an epidermis-specific conditional Lis1 knockout mouse, I found that Lis1 is required for cortical microtubule organization. Surprisingly, however, Lis1 is also required for desmosome stability. This work reveals essential desmosome-associated components that control cortical microtubule organization and unexpected roles for centrosomal proteins in epidermal function.
Although Lis1 is required for microtubule organization, it is not sufficient. I created a culture-based system to determine what other factors may be required for cortical organization for microtubules. My work reveals that stabilization of the microtubules is sufficient to induce their cortical organization. Functionally, cortical microtubules are important for increasing the mechanical integrity of cell sheets by engaging adherens junctions. In turn, tight junction activity is increased. Therefore, I propose that cortical microtubules in the epidermis are important in forming a robust barrier by cooperatively strengthening each cell-cell junction.
To determine whether desmosomes play similar roles in simple epithelia as stratified epithelia, I examined intestinal epithelial-specific conditional desmoplakin conditional knockout mice. Unexpectedly, I found that desmoplakin is not required for cell-cell adhesion and tissue integrity in the small intestine. Furthermore, it does not organize intermediate filaments. Desmoplakin is required, however, for proper microvillus architecture.
Overall, my studies highlight novel tissue-specific roles for desmosomes, in particular desmoplakin, in organizing and integrating different cytoskeletal networks. How desmoplakin's function is regulated in each tissue will be a new interesting area of research.