UBIR Repository (Univ. at Buffalo)
Not a member yet
5736 research outputs found
Sort by
The Mechanism of Cadmium Removal from Renal Cell Model Mediated by GMDTC
No full textM.S.Cadmium (Cd) is classified as a known human carcinogen (IA Class) by the International Agency for Research on Cancer (IARC). Cadmium combines with metallothionein to form a complex which is transferred through blood circulation to the kidneys. Such complexes degrade in lysosomes and release free cadmium ions which cause the loss of calcium and vitamin D, leading to osteoporosis, diabetes, reproductive system problem, and other severe diseases. However, the body lacks the effective mechanisms to clear cadmium ions. Currently, the use of common chelating agents, e.g., EDTA, BAL, has proven disappointing due to their severe side effects and/or ineffectiveness in removing cadmium from the kidney. GMDTC, a newly synthesized DTC (dithiocarbamate) derivative, has been shown to be safe (very low toxicity) and efficient in removing cadmium and other metals from the kidneys of the mouse, rat, and rabbit, as well as from human proximal tubule cells (HK-2). The objective of this project is to clarify the mechanism of cadmium excretion mediated by GMDTC utilizing CRISPR/Cas9 technology to construct SGLT2, GLUT2 single and double-gene knockout (SGLT2-/-, GLUT2-/-, SGLT2-/-/GLUT2-/-) in HK-2 cell lines. These constructed models were used to investigate GMDTC and its potential to reduce cadmium-induced renal toxicity in vitro. The ability of GMDTC to react with cadmium to form a GMDTC-cadmium complex was shown through UV-VIS spectroscopy. It was observed that co-treatment of cadmium with GMDTC could increase cell viability in HK-2 cell line and decrease cadmium-induced toxicity. Cell viability also increased in cells treated with cadmium and GMDTC in GMDTC rescue experiments, indicating that GMDTC could attenuate cadmium-induced toxicity caused by intracellular cadmium accumulation. We hypothesize that the mechanism of cadmium removal from the kidney by GMDTC is through the glucose reabsorption pathway, consisting of SGLT2 and GLUT2 glucose transporters. We developed the CRISPR/Cas9 mediated SGLT2, GLUT2 single and double gene knockout cell lines from HK-2 cells. This served to determine the role of glucose reabsorption pathway in GMDTC’s ability of removing cadmium from kidney cells. Validation of successful knockouts was conducted using flow cytometer, western blot analysis, Sanger sequencing analysis, and Tracking of Insertions and Deletions by decomposition (TIDE) analysis. Two monoclonal cell lines for the single gene knockout and one for the double gene knockout were used for later experiments. Compared to control, cell viability decreased in both single and double gene knockout cell models in GMDTC rescue experiments, which indicates that GMDTC may not enter into cells and/or the GMDTC-cadmium complex cannot discharge from cells after SGLT2 and GLUT2 gene knockouts. Removal of cadmium from cells by GMDTC may rely on the assistance of these two glucose transporters. To verify this mechanism, two chemical inhibitors of SGLT2 and GLUT2 were used to assess the effects of GMDTC in reducing cadmium-induced toxicity in HK-2 cells. Cell viability significantly decreased with inhibition of either SGLT2 or GLUT2 protein carrier, suggesting that as a result of the inhibition of glucose transporters, GMDTC could not get into cells to form the GMDTC-cadmium complex which then would be excreted from cells. In summary, these results indirectly indicate that GMDTC protects against cadmium-induced toxicity by preventing the accumulation of cadmium in renal cells and by removing intracellular cadmium via the glucose reabsorption pathway. In conclusion, the results of this study suggest that GMDTC reduces cadmium-induced renal toxicity by preventing the accumulation and assisting in the removal of intracellular cadmium. The potential mechanism of GMDTC in removing cadmium in vitro is likely mediated by the glucose transporters, SGLT2 and GLUT2. Therefore, GMDTC may be clinically useful for the prevention of cadmium poisoning.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
The Experiences of Black and Latinx Graduate Students in STEM: A Critical Race Perspective
No full textPh.D.Students of color pursuing STEM undergraduate degrees show higher aspirations to continue on to graduate school, but are less likely to do so than their counterparts. As students move on from undergraduate to graduate education, racial disparities become more pronounced with less students of color found at both the master's and Ph.D. levels. Previous work focuses on the perceived deficits of students, rather than on the systemic racism embedded in STEM that leads to the exclusion of Black, Indigenous and people of color (BIPOC). To get a better understanding of how racism affects the experiences and pathways of students of color in STEM, I conducted in-depth interviews and a focus group with 31 Black and Latinx students in STEM master's and Ph.D. programs. Using critical race theory, socialization theory, and an anti-deficit framework, findings showed that: 1. Black and Latinx students benefit greatly from support programs geared to STEM students of color because they provide alternative ways for students to access the resources, opportunities and networks that help students build strong science identities and affirm their social identities leading them to enroll in graduate school; 2. Stereotype threat is exacerbated by Black and Latinx students' experiences with racist and sexist microaggessions in graduate school from faculty and peers, and students respond by resisting assimilation into the dominant STEM culture and creating counter-narratives to negative stereotypes while continuing to affirm their racial and ethnic identities; 3. The ideology of universalism in STEM promotes colorblindness that erases the experiences of Black and Latinx students and creates tension in departments, leaving students with a lack of peer support and a heavier reliance on faculty for successful socialization into the STEM academic community. Overall, this research study adds to the conversation on STEM education and diversity in STEM, and offers a different perspective that refocuses attention on structural changes that benefit aspiring scientists and engineers from historically underrepresented backgrounds.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
Combined Development of Constraint Based Flux Analysis and Sensitivity Analysis for the Study of Glycosylation Pathways
No full textPh.D.The glycome constitutes the entire complement of glycans and glycoconjugates that compose a cell or tissue. With the advent of new high-throughput technologies, vast amounts of data related to the glycome are being collected using different modalities, such as transcriptome data collected using RNA-Seq and glycome data using mass spectrometry. Glycomics data, measured using mass spectrometry, reflects the underlying biochemistry of the cell/tissue, and the glycosylating enzyme active in the system. It would be attractive to develop a series computational tools to understand the underlying enzymatic reaction network based on glycome profiling and to integrate knowledge from different experimental techniques. To address this need, we have developed a pipeline for the glycomics data analysis, visualization and prediction. To fully understand the roles of glycoenzyme in the biosynthesis of the glycans, a MySQL based glycoenzyme database, including glycosyltransferase, glycosidase, epimerase and sulfotrasferase, was manually curated as the foundation for the whole project. A MATLAB based toolbox for MALDI-TOF (matrix-assisted laser desorption/ionization-time of flight) dataset analysis was developed to annotate and quantitatively analyze glycomics data collected from different experiments. And last a constrained-based glycosylation flux analysis (cGFA) algorithm was provided to explore the underlying mechanism behind the glycosylation networks and to predict the enzyme activities by iteratively fit the simulation results to experiment data to finally create a baseline model for different cell or tissue system. Overall, the modeling framework provides a straightforward strategy to understand the underlying enzymatic reaction network based on glycome profiling collected using mass spectrometry data.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
Evaluating the Neuropathology of a Rat Model of Progressive Supranuclear Palsy
No full textM.S.Progressive Supranuclear Palsy (PSP) is the most common atypical parkinsonism. Symptoms of this fatal neurodegenerative disease include motor impairment, postural instability, acoustic startle reflex deficits, and speech problems. Cognitive symptoms such as dementia, apathy, depression, and anxiety also occur in PSP. The pedunculopontine tegmentum (PPTg), a superior brainstem structure, has become a focus in the study of Parkinsonisms such as PSP. Pathologically, PSP shows an early extensive loss of PPTg cholinergic neurons, as well as aggregates of the microtubule-stabilizing protein tau, which are greatest in areas innervated by the PPTg. This suggests the PPTg may be an early node in disease progression and a target structure for novel therapeutics. Currently, there are no pharmacotherapies available for PSP patients, and drug discovery is hindered by the lack of an adequate preclinical model. Previously, selective cholinergic PPTg lesions in rats induced PSP-like symptomology and pathology including motor deficits, a significantly reduced acoustic startle reflex, substantia nigra (SN) dopaminergic loss, and enlarged lateral ventricles. However, lesioned rats showed no evidence of pathological tau. Building upon previous efforts, we hypothesize that the loss of PPTg cholinergic neurons, coupled with deposition of tau in areas seen in PSP, will mimic PSP symptomology and pathology. To achieve this, male and female ChAT-Cre Long Evans rats were injected in the PPTg with a virally mediated (adeno associated virus) human 1N4R tau construct (tau isoform implicated in PSP). GFP constructs were used as a control. Following surgery, rats were tested in a battery of behavioral paradigms. As early as four weeks post-surgery rats exhibited significant PSP-like motor impairments, ASR deficit, and increased anxiety-like behavior, which did not diminish over the duration of 20 weeks. Six months post-surgery, brains were taken for histological analysis. ChAT immunohistochemistry confirmed that expression of human WT 1N4R tau in the cholinergic PPTg is sufficient to produce loss of cholinergic PPTg neurons. This pathology also precipitated loss of dopaminergic SN neurons, recapitulating the results of the lesion model. In addition to neurodegeneration of areas affected in PSP, tau pathology was also observed. Hyperphosphorylated tau and abnormal conformation tau were confirmed to be present in the brainstem. Abnormal confirmation tau was also observed in the SN, a structure directly innervated by the PPTg. Although further studies are required to confirm neuron-to-neuron propagation of tau, this finding supports our hypothesis and suggests tau is spreading along PPTg projections, producing neuron loss relevant to PSP. Thus far, both behavior and histology results indicate the induction of tau in the cholinergic PPTg may be an adequate animal model for PSP. The validation of this model will aid in future PSP research and facilitate drug discovery.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
Developing A Standardized Patient Hand-Off Communication Tool for Nurse Practitioners and Physician Assistants Working in Four Medicine Units in a Large University-Based Teaching Hospital In New York
No full textUB SON, DNP Research ProjectInpatient settings often lack standardized patient hand-off communication tools which can lead to omission of patient care details, delays in treatment, and increased risk for serious medical er-rors. A review of the literature revealed a lack of evidence regarding effective patient hand-off communication tools among advanced care providers (ACPs) working in inpatient settings. With increased utility of ACPs in hospital settings, specifically Nurse Practitioners (NPs) and Physi-cian Assistants (PAs), communication processes require close evaluation and consideration to allow for ongoing safe patient care. The purpose of this Doctor of Nursing Practice (DNP) pro-ject was to explore the perceived barriers and communication needs regarding patient hand-off among NPs and PAs working in four medical units in a large university-based teaching hospital in New York to update the current patient hand-off process. Using a mixed method design, two semi-structured focus group interview sessions were conducted with 15 medicine NPs and PAs to explore barriers of the current electronic medical record (EMR) generated patient hand-off communication tool at the project site. Based on focus group findings, a revised electronic medi-cal record (EMR) generated patient hand-off communication tool was developed and pilot-tested for one month. Following the pilot test, an online survey was administered to the medical unit NPs and PAs to assess efficacy of the revised tool and to evaluate its utility as a standardized communication hand-off tool. Future research should be conducted after tool implementation to evaluate its effectiveness among the NPs and PAs and to assess improvement in patient care quality
Improving Anesthesia Non-Technical Skills in Nurse Anesthetists Through an Online Workshop
No full textUB SON, DNP Research ProjectSeventy percent of critical errors in anesthesia result from poor provider anesthesia non-technical skills (ANTS) indicating a critical need to examine alternative methods promoting ANTS. This Doctor of Nursing Practice (DNP) project examined the impact of an online educational ANTS workshop created for New York Certified Registered Nurse Anesthetists (CRNAs) who precept student registered nurse anesthetists (SRNAs). Lewin’s Theory of Planned Change was the theoretical framework. CRNAs were recruited using convenience snowball sampling through professional Facebook pages and the University at Buffalo LISTSERV. An online pre-workshop survey (n = 38), followed by an online self-guided workshop, focused on current ANTS information including the current definition, clinical implications, the perioperative role, and the importance of CRNAs training SRNAs about ANTS. A post-educational survey was administered immediately following the workshop (n = 29) and again one month later (n = 22). Data were analyzed using a one-way ANOVA rank test and chi square test of independence. Following the educational workshop, there was a statistically significant decrease in CRNAs’ perceived effectiveness in training SRNAs’ ANTS (p = 0.003). CRNAs perception of the importance of ANTS in non-crisis situations was statistically significant, increasing over time (p = 0.003 & p = 0.001). Forty percent of CRNAs reported personalities as a perioperative ANTS barrier. Knowledge was not perceived as a factor contributing to ANTS deficits. ANTS barriers reported by the CRNAs pointed toward the culture in the perioperative period. Introducing a no blame environment may increase the use of ANTS and improve patient outcomes
Comparing Wait Times and Outcomes in Adult Oncology Patients with Febrile Neutropenia in the Emergency Department: A Retrospective Analysis
No full textUB SON, DNP Research ProjectDue to the rapidly increasing elderly population and to the advancements in oncology,
there has been an increase in the diagnosis of cancer, and also a rise in oncologic emergencies.
Chemotherapy and immunotherapy are increasingly being used in people with advanced cancer
to palliate symptoms and improve survival and quality of life. However, research found that over
50% of patients receiving outpatient chemotherapy will have an ED visit, presenting with greater
clinical complexity, higher admission rates and have higher morbidity and mortality at that
admission. Furthermore, the side effects experienced from the cancer itself or its’ treatment can
be life threatening if not addressed adequately. Research findings indicate that the acute care,
non-specialized environment of an emergency department (ED) is not conducive for providing
complex care to a patient with cancer who is in need of an immediate intervention for an acute
issue. The objective of the retrospective chart review was to compare patient outcomes in regards
to wait time for adult oncology patients age 50-89 with neutropenic fever in the emergency
department. The RE-AIM model has been selected to guide this project proposal. A retrospective
chart review was performed in order to measure outcomes for febrile neutropenic patients such
as hospital length of stay, sepsis and mortality. Results yielded a significant relationship between
age and time to antibiotic (TTA) but not for TTA and increased length of stay, increased
incidence of sepsis or increase in mortality. More research is needed to address symptom
management in an acute care setting in this specialized population
"Ready-Ready" to Teach: The Telling Case of a Reflective Teacher-Practitioner
No full textThis qualitative telling case study was situated within a broader project, which explored how the research participants modified their teaching after having completed their master’s program. We investigated reflective stance of a teacher-practitioner who was a graduate of a Master’s Literacy Specialist program, which promoted reflective teaching practices using videos of students’ own teaching. The research questions were: (1) How does the participant demonstrate his use of a reflective stance with regard to teaching practices? (2) What are the modifications in teaching practices that were made by the participant after the reflective video pedagogy course used in his graduate practicum? (3) What other elements of his graduate program does the participant describe as being important in his development as a reflective practitioner? (4) Which of these elements does he choose to employ in his classroom? Primary data sources included: classroom observations, participant interviews, and student artifacts. We analysed the data using qualitative methods of open coding, thematic analysis, and triangulation. The research found that the focus-participant reported a series of modifications made by him to his teaching and demonstrated his use of reflective stance on the high mastery level
Data supporting "Challenges in predicting Greenland supraglacial lake drainages at the regional scale"
No full textA leading hypothesis for the mechanism of fast supraglacial lake drainages is that transient extensional stresses briefly allow crevassing in otherwise-compressive ice flow regimes. Lake water can then hydrofracture the crevasse to the base of the ice sheet, and river inputs can maintain this connection as a moulin. If future ice-sheet models are to accurately represent moulins, we must understand their formation processes, timescales, and locations. Here, we use remote-sensing velocity products to constrain the relationship between strain rates and lake drainages across ~1600 km2 in Pâkitsoq, western Greenland, between 2002–2019. We find significantly more-extensional background strain rates at moulins associated with fast-draining lakes than at slow-draining or non-draining lake moulins. We test whether moulins in more-extensional background settings drain their lakes earlier, but find insignificant correlation. To investigate the frequency that strain-rate transients are associated with fast lake drainage, we examined Landsat-derived strain rates over 16- and 32-day periods at moulins associated with 240 fast lake drainage events over 18 years. A low signal-to-noise ratio, the presence of water, and the multi-week repeat cycle obscured any resolution of the hypothesized transient strain rates. Our results support the hypothesis that transient strain rates drive fast lake drainages. However, the current generation of ice-sheet velocity products, even when stacked across hundreds of fast lake drainages, cannot resolve these transients. Thus, observational progress in understanding lake drainage initiation will rely on field-based tools such as GPS networks and photogrammetry.NASA Postdoctoral Program (NNH15CO48B), NASA Cryospheric Sciences Program (grant 80NSSC19K0054