MEDICA@MUSC (Medical University of South Carolina)
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Tracking Professional Growth: Developing a Digital Professional Portfolio Training
Get PDFBackground: Creating a professional portfolio is important for promotion, tenure, annual evaluation, and professional certification. As an early career health sciences librarian, I was advised to track my accomplishments as they happened to make applying for a promotion easier in the future. After successfully creating and utilizing a digital professional portfolio of my own, other librarians asked me to teach them how to develop digital portfolios. An in-service program was created that would provide training, support, and a template for both new and experienced library faculty.
Description: After investigating options for an electronic method of organizing and tracking my professional accomplishments, I chose Microsoft OneNote for its user-friendly interface, level of customization available, and integration with existing Microsoft programs. In 2021, the library hired several first-time faculty members who were not familiar with the need to create a professional portfolio. It was decided that the first in-service training session would be offered to this group. The training, which would provide an explanation of the portfolio and potential uses, was scheduled. This session also included a hands-on demonstration of both an active portfolio and the blank template. Future sessions have been scheduled to provide the in-service training and template to remaining library faculty. The blank template has also been shared with faculty outside of the institution – but no external training has been provided at this point.
Conclusion: The digital portfolio in OneNote was successfully used for the self-assessment portion of my annual evaluation, applying for AHIP, and achieving two MLA specializations. While the program is still on-going, comments regarding increased organization and effectiveness have been received and have been overwhelmingly positive. Outcomes that I am expecting to measure include: whether the digital portfolio helped with tracking professional accomplishments, if the portfolio was used to apply for any certifications or specializations, if it was helpful when completing an annual evaluation, and if other uses have been discovered for the portfolio. These outcomes will be measured by an anonymous survey distributed to in-service attendees who have also received the blank template
Social and Clinical Factors Associated with End-Stage Renal Disease (ESRD): A Retrospective Cohort of Older Adult Veterans with Severe Chronic Kidney Disease (CKD)
No full textAs the aging population continues to grow so does the prevalence of chronic kidney disease (CKD) and the need for adequate CKD management in those 65 or over who are highly heterogenous in their disease progression. Hospitalization rates for acute kidney injury (AKI) are increasing, especially amongst older adults (≥65) who are at elevated risk given their high comorbidity burden and susceptibility to nephrotoxins. Previous epidemiologic analyses of AKI have focused on hospitalized populations which may bias results towards sicker populations; particularly when results are extrapolated to ambulatory CKD populations. Studies on social determinants of health (SDOH) and disease progression in CKD populations are limited, both in number and range of key areas, especially among older adults who become more vulnerable to stressors as they age. To fill these gaps in the literature, we obtained information on select social and clinical factors and examined their relationship with progression to end-stage renal disease (ESRD) in Veterans ≥65 years of age with incident CKD stage 4 using national VA administrative data. We hypothesize several points: first, that AKI is associated with ESRD, and age is an effect modifier of this relationship; second, an AKI and a rapidly declining kidney function are jointly associated with ESRD; third, a high social vulnerability at the census tract level based on the CDC’s Social Vulnerability Index (SVI) is associated with ESRD. This dissertation identified several clinically relevant joint effects associated with ESRD. However, more Veterans died than progressed to ESRD. Traditional methods of CKD management through means of achieving appropriate target controls can help mitigate the risk of death in this population who have a high comorbidity burden. Outsourcing to primary care or specialty care to alleviate the burden on nephrology should be considered in this group
The Relationship between Racially Minoritized Individuals and Cardiac Implantable Electronic Device Infections
No full textIntroduction: Cardiac implantable electronic device (refers to any permanent implantable cardiac pacemaker, cardioverter defibrillator, or cardiac resynchronization therapy device. Of the more than 300, 000 individuals that receive CIED implants every year in the United States, 1% will develop a CIED infection. Methods: A search of peer reviewed literature in Scopus and PubMed from 2010 through 2022 was performed. Results: Of the 10 reviewed articles, two evaluated race and found non-white ethnicity to be a factor for CIED infection. Several reviewed articles found risk factors for CIED infection to include post operative hematoma, male gender, diabetes, renal failure or end stage renal diseases, and heart failure. Conclusion: There needs to be further research on the relationship between CIED infection and race.https://medica-musc.researchcommons.org/posters/1018/thumbnail.jp
Vaccinia Virus DNA Metabolism: The Contributions of the Cellular Milieu and Novel Roles of the Viral DNA Replication Machinery Following Exogenous DNA Damage
Get PDFPoxviruses are large dsDNA viruses, unique in their cytoplasmic replication. This autonomy from the host nucleus poses novel challenges to genome replication, recombination and repair. Biochemical and genetic studies have confirmed that the viral genome encodes a repertoire of replication components (polymerase, processivity factor, single-strand DNA binding protein, primase/helicase, DNA ligase, scaffold protein). However, our knowledge of the mechanism of viral DNA replication remains incomplete, as is our understanding of which, if any, cellular proteins participate. We have shown that infection does not induce or dampen the cellular DNA damage response, but that a key component of this response, the ATR protein kinase, plays a role in viral genome replication. Inhibition of ATR destabilizes the small subunit (RRM2) of the cellular ribonucleotide reductase, delays the accumulation of nascent viral genomes, and results in the accumulation of subgenomic viral DNA fragments. To understand how vaccinia virus responds to exogenous DNA damage, we subjected cells to UV irradiation prior to (-1 hpi) or during (4 hpi) infection. Pre-irradiation of cells decreased protein synthesis and led to an ~12-fold reduction in viral yield. In addition to these cell-specific insults, irradiation at 4hpi introduced both CPD and 6-4-PP lesions into the viral genome, halted further DNA synthesis and led to a greater, ~35-fold reduction in viral yield. DNA lesions persisted throughout infection and were indeed present in the genomes encapsidated into nascent virions. Depletion of several components of the cellular nucleotide excision repair (XP-A, -F, -G) did not render infections hypersensitive to UV. However, infections performed with viruses lacking the cellular DNA ligase (A50) or structure specific nuclease (G5) were hypersensitive to UV irradiation (~3-fold and ~100-fold, respectively). When the DNA polymerase inhibitor araC was added to WT infections at the time of UV irradiation (4 hpi), hypersensitivity to UV irradiation was also seen (~10-fold). Virions produced under the latter condition contained elevated levels of CPD adducts, strongly suggesting that the viral polymerase can remove or repair UV lesions introduced into the viral genome
Comparison of Accuracy and Efficiency of Robotic-Assisted Haptic Guidance versus Freehand Access Preparation in Calcified Teeth
Get PDFIntroduction: The initial step of root canal therapy consists of access preparation. Access preparation can be difficult, due to pulpal calcifications, misaligned teeth, and full coverage restorations that obscure the canal morphology. Recent trends involve static or dynamic guides to help the operator to locate the canals. Both systems have limitations. A robot with haptic guidance has been developed for implant surgeries, however, no studies have evaluated its possible use in endodontics. The purpose of this study was to determine whether the volume of tooth structure removed, and time required for access preparation in calcified anterior teeth differed between a robot-guided approach compared to freehand access. Methods: Forty-eight maxillary and mandibular anterior teeth with calcified canals were randomly divided into 3 groups (by number allocation). Teeth were mounted and a preoperative CBCT taken. Access cavity preparation was performed with robot-guided approach after planning the procedure in group 1 (robot-guided by a second-year endodontic resident), and freehand in groups 2 (experienced endodontist) and 3 (second-year endodontic resident). Time in seconds was recorded and a postoperative CBCT was obtained. Digital Imaging and Communications in Medicine (DICOM) images were transferred to ITK-SNAP software (an application used to segment structures in 3D medical images) to evaluate the percentage volume of tooth structure removed. Statistical analyses consisted of independent samples t-tests and one-way Analysis of Variance (ANOVA). Results: Forty teeth were used for final analyses. Seven teeth were excluded from the analysis due to gouging, perforation or broken bur in robot-guided group and one tooth was excluded from endodontic resident freehand group due to perforation. Regarding time, mean measures for group 1, 2 and 3 were 74.3, 144.9 and 219.9 seconds, respectively. There is a significant difference between group 1 and group 2 (p0.05). Mean percentages for volume of tooth structure removal in mm3 were 3.7, 8.1 and 9.5, for groups 1, 2 and 3 respectively. Significant differences are observed between group 1 and group 2 (p0.05). Conclusions: Robot-guided navigation can be an efficient alternative for accessing calcified teeth if procedure is planned accurately. More research is needed in the future for better results
Removal of Endodontic Fiber Posts Using Robot-Assisted Haptic Guidance: A Novel Approach
Get PDFIntroduction: Fiber posts are frequently used for the restoration of endodontically treated teeth. Such posts are typically bonded to the tooth using a composite resin system. These posts often need to be removed during endodontic retreatment. While there are many techniques to remove fiber posts, most include drilling through the post itself which can be challenging and result in a perforation or excessive tooth structure being removed. Static and dynamic guided endodontic techniques have been proposed to safely remove fiber posts. Yomi (Neocis, Inc, Miami, FL) is a haptic robot guidance system has been FDA approved to assist in placing dental implants and may be able to be used for endodontic applications. This system combines the advantages of both static and dynamic guidance. The purpose of this study was to investigate the ability and efficiency of a robot-assisted haptic guidance system to remove bonded fiber posts in endodontically treated teeth. Methods: Forty-six natural extracted single-rooted maxillary anterior teeth with straight canals were selected and endodontically treated. Following obturation, a post space was created, and fiber posts placed and bonded with resin. The teeth were then mounted in acrylic blocks simulating a maxillary arch form. Preoperative CBCT volumes were acquired. The teeth were divided into 3 groups for fiber post removal. In Group 1 the fiber posts were removed by an endodontic resident using robot-assisted haptic guidance. In Group 2 the fiber posts were removed by an experienced endodontist using a freehand technique. In Group 3 the fiber posts were removed by the endodontic resident using a freehand technique. The volume of removed tooth structure was measured and time to remove the fiber posts recorded. Post-operative CBCT volumes were acquired. ITK-SNAP semiautomatic segmentation software was used to compare pre- and post-operative CBCT images for volumetric analysis in determining the amount of tooth structure removal. The data was statistically analyzed using independent samples t-tests, one-way ANOVA, and the Tukey post-hoc procedure. Results: All teeth were included for final analyses. The mean time to remove a post in Group 1 was 33.3 seconds, Group 2 was 446.2 seconds, and Group 3 was 607.2 seconds. There was a significant difference between each group regarding the time to remove the fiber post. The mean volume of tooth structure removed in Group 1 was 10.9 mm3, Group 2 was 15.6 mm3, and Group 3 was 24.3 mm3. The difference in volume of tooth structure removed was significant between Group 1 and the two other groups. Conclusions: The removal of resin bonded fiber posts in single canal maxillary teeth is possible using a robot-assisted haptic guidance system. The robot guided system is more time efficient and results in less volume removed when removing fiber posts compared to freehand techniques. An experienced endodontist is more conservative in removing a fiber post than an endodontic resident when considering the amount of tooth structure removed
An Imaging Mass Spectrometry Investigation Into the N-linked Glycosylation Landscape of Pancreatic Ductal Adenocarcinoma and the Development of Associated Tools for Enhanced Glycan Separation and Characterization
Get PDFThe severity of pancreatic ductal adenocarcinoma (PDAC) is largely attributed to a failure to detect the disease before metastatic spread has occurred. CA19-9, a carbohydrate biomarker, is used clinically to surveille disease progression, but due to specificity challenges is not suitable for early discovery. As CA19-9 and other prospective markers are glycan epitopes, there is great clinical interest in understanding the glycobiology of pancreatic cancer. Unfortunately, few studies have been able to link glycosylation changes directly to pancreatic tumors and instead have focused on peripheral glycan alterations in the serum of PDAC patients. To address this gap in our understanding, we applied an imaging mass spectrometry (IMS) approach with complementary enzymatic and chemical isomer separation techniques to spatially assess the PDAC N-glycome in a cohort of pancreatic cancer patients. Orthogonally, we characterized the expression of CA19-9 and a new biomarker, sTRA, by multi-round immunofluorescence (IF) in the same cohort. These analyses revealed increased sialylation, fucosylation and branching amongst other structural themes in areas of PDAC tumor tissue. CA19-9 expressing tumors were defined by multiply branched, fucosylated bisecting N-glycans while sTRA expressing tumors favored tetraantennary N-glycans with polylactosamine extensions. IMS and IF-derived glycan and biomarker features were used to build classification models that detected PDAC tissue with an AUC of 0.939, outperforming models using either dataset individually. While studying sialylation isomers in our PDAC cohort, we saw an opportunity to enhance the chemical derivatization protocol we were using to address its shortcomings and expand its functionality. Subsequently, we developed a set of novel amidation-amidation strategies to stabilize and differentially label 2,3 and 2,6-linked sialic acids. In our alkyne-based approach, the differential mass shifts induced by the reactions allow for isomeric discrimination in imaging mass spectrometry experiments. This scheme, termed AAXL, was further characterized in clinical tissue specimens, biofluids and cultured cells. Our azide-based approach, termed AAN3, was more suitable for bioorthogonal applications, where the azide tag installed on 2,3 and 2,8-sialic acids could be reacted by click chemistry with a biotin-alkyne for subsequent streptavidin-peroxidase staining. Furthering the use of AAN3, we developed two additional techniques to fluorescently label (SAFER) and preferentially enrich (SABER) 2,3 and 2,8-linked sialic acids for more advanced glycomic applications. Initial experiments with these novel approaches have shown successful fluorescent staining and the identification of over 100 sialylated glycoproteins by LC-MS/MS. These four bioorthogonal strategies provide a new glycomic tool set for the characterization of sialic acid isomers in pancreatic and other cancers. Overall, this work furthers our collective understanding of the glycobiology underpinning pancreatic cancer and potentiates the discovery of novel carbohydrate biomarkers for the early detection of PDAC
Exploring Late Adopter Motivation: A Corona Virus (COVID-19) Vaccine Quality Improvement Project
Get PDFLower than ideal COVID-19 vaccination rates are problematic nationally. As of March 4th, 2022 65% of eligible Americans were fully vaccinated (CDC, 2022). South Carolina fell below the national rate with only 57% of eligible South Carolinians were fully vaccinated at the same time period (SCDHEC, 2022). Both rates are below the national goal that was set for nation of 70% of eligible Americans being fully vaccinated by July 4th, 2021. This project aimed at exploring the motivation of individuals who would be considered late adopters. It was found that motivation to become vaccinated was varied and personal. The conclusion was that vaccination communication should be culturally appropriate and personalized for the best outcome
Elucidating the Effects of ERα: Isoform Expression and Differential Receptor Localization in Immune Function
Get PDFEstrogen can be anti- or pro-inflammatory depending on milieu and has a role in increased incidence of lupus in reproductive age women versus men. Estrogen’s pleiotropic effects are in part due to Estrogen receptorα (ERα) and its variants that localize to cytoplasmic pools, nuclear regions and to the membrane. To understand the role of sex hormone receptors in immune responses, we investigated the effects of altered ERα isoform overexpression in dendritic and B cells. Toll like receptor 7 (TLR7) stimulated endpoints, often dysregulated in lupus were also investigated. Genetically modified MOER (membrane-only ERα) and NOER (nuclear-only ERα) mice were used to investigate the effects of membrane versus nuclear ERα. Transfection experiments were conducted using the Neon Electroporation system. In vitro studies utilized transfected DC2.4 cells (a murine dendritic cell line) as well as a human SLE EBV-transformed B cell line. Transfected cells were stimulated with TLR7 agonist for 1.5 hours and used either for vitality assays or RNA processed for Nanostring analysis. Bone marrow harvested from ovariectomized NOER mice cultured with GM-CSF and IL-4 for 7 days to generate BM-DCs, also treated for 1.5 hrs with TLR7 agonist and stained to observe NFκB p65 translocation. Preliminary results show that cells overexpressing ERα46 compared to ERα66 differentially express multiple genes critical in inflammation and immunity. Top genes altered in DC2.4 include IL1α and IL1β. Interestingly, ERα 46:66 co-expression was similar in DC2.4 while B cells resulted in significant downregulation in genes such as Nfatc3 and Hif1a. Nanostring analysis has started to highlight altered pathways such as NFκB and MAPK. WST-1 assays suggests that ERα66 is more proliferative. NOER BM-DC stains show little to no translocation of NFκB p65 to the nucleus before or after stimulation suggesting membrane ERα is necessary. Continued studies are needed to clarify the role of ERα isoform expression and localization in immune cell function. Results between B cells and DCs highlight the ability for ERα to act on different immune cells. These recent data share similarities in altered genes previously seen in RNAseq of BM-DCs from ERα short mice supporting a connection between ERα short and ERα46
The Impact of Protein Tyrosine Phosphatase 1B on Impaired Insulin Signaling and Cognitive Impairment
Get PDFHigh-fat diet (HFD) in mice, a mouse model of diet-induced obesity, display cognitive deficits, which correlate with hyperinsulinemia and reduced levels of brain insulin. The binding of insulin to the insulin receptor leads to tyrosine auto-phosphorylation of the receptor, which is a necessary step for the initiation of insulin transport. Protein tyrosine phosphatase 1B (PTP1B) dephosphorylates tyrosine residues on the Insulin receptor. We hypothesize that diet-induced increases in PTP1B levels inhibits insulin receptor signaling contributing to cognitive impairment. To accomplish this, PTP1B levels, tyrosine phosphorylation, and cognition was assessed in mice placed on either a standard diet (STD) or HFD for 12-24 weeks of diet treated with either saline (control) or Claramine (10-180g), a specific and selective PTP1B inhibitor. After 12 weeks of diet, PTP1B levels were increased in HFD mice compared to STD mice. A single intraperitoneal dose of Claramine (180g) reduced PTP1B levels and increased tyrosine phosphorylation of the Insulin receptor in the hippocampus. HFD mice display cognitive deficits using a problem-solving task, the Puzzle Box; however, Claramine treatment delivered via mini osmotic pumps, improved cognitive deficits in HFD mice compared to STD mice. Postmortem hippocampal tissue analysis revealed no significant differences in PTP1B levels nor the expected increase in tyrosine phosphorylation in HFD mice treated with Claramine. Given that the hippocampus contains multiple cell types, we investigated the impact of hyperinsulinemia, to mimic HFD in vitro, on PTP1B, tyrosine phosphorylation of the Insulin receptor, and downstream insulin signaling in primary brain endothelial cells, one of the main cell types involved in mediating Insulin receptor transport from the periphery to the brain. PTP1B levels are increased in hyperinsulinemic cells and reduced in hyperinsulinemic cells treated with Claramine. While there are no significant differences in tyrosine phosphorylation there is a trending decrease in hyperinsulinemic cells with trending increase in hyperinsulinemic cells treated with Claramine. Overall, our data demonstrates that Claramine is an effective inhibitor of PTP1B in vivo and in primary endothelial cells and can improve diet-induced cognitive deficits; however, additional studies are warranted