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Vestibular Evoked Myogenic Potentials and Postural Control in Adults with Age-Related Hearing Loss
Get PDFIt is well-documented that auditory thresholds decrease with age, which can be referred to as Age-related hearing loss (ARHL). ARHL is one of the most common conditions affecting older adults and is associated with several conditions including decreased postural stability and falls. Age-related changes to auditory function have been attributed to, through histopathological study, specific degradation of the sensory, supporting, and afferent structures of the cochlea. Vestibular function, as measured through vestibular evoked myogenic potentials (VEMPs) also show decreases with age. VEMPs are a measurement of evoked potentials generated by auditory stimulation of the utricle and saccule measured through a reduction in muscle potentials. Similar to ARHL, age-related changes to the vestibular sensory and supporting structures with specific degeneration of the saccule, utricle, otoconia, primary vestibular afferents have also been noted. Significant decreasesin postural control with age are also well-documented in literature attributed to multifactorial changes in function. Previous studies have found associations between vestibular dysfunction and hearing loss in specific pathologies. Additional associations between ARHL and decreased postural control have also been documented. However, only limited data has been reported evaluating the association of ARHL, decreased vestibular function, and postural control.
The results of this study indicated significant differences in VEMP findings for individuals with ARHL compared to an age-matched group with normal hearing. Additionally, significant correlations were noted across groups with decreases in hearing thresholds associated with decreases in VEMP amplitude and prolongation of VEMP latency. No significant differences between the ARHL and normal hearing group were noted for postural control measures. No significant correlations were noted for hearing thresholds and postural measures. These results are consistent with previous literature describing concomitant vestibular dysfunction in ARHL and other types of SNHL. The long-term goal of this line of this study is to evaluate the use of auditory function as a predictor of increased risk of falls and a possible criterion for subsequent balance function testing and intervention as needed as a means to reduce the risk and occurrence of falls in people with ARHL
The Effects of Dual-Tasking on Fall Risks in Adults with Brain Injury
Get PDFClinical Scenario: Dual-tasking combines both physical and cognitive components into one therapeutic intervention. There has been limited research on the benefits of dual tasking in relation to fall risks in adults with brain injury. Currently, it is common for various therapy interventions to spend the majority of time targeting physical or cognitive components, but not both at once. After appraisal, a total of five articles were used. These included two level I studies involving a high-quality randomized control trial and a meta-analysis, two level II studies that were both small-scale randomized control trials, and one level IV study that was a case study. The clinical bottom lines provided stated that strong evidence suggests that dual-tasking decreases fall risks in adults with brain injury, effective interventions ranged from 3 times per week for 60 minutes over 8 weeks to 7 times per week for 15 minutes over 1 week, and for adults with brain injuries, there is potential for carryover into everyday life after dual-tasking activities. The recommendations for implementation stated that further research is needed to determine the effectiveness of dual-tasking for reducing fall risks and close monitoring of the effects of dual-tasking during intervention is recommended
Understanding Human Astrovirus from Pathogenesis to Treatment
Get PDFWhile human astroviruses (HAstV) were discovered nearly 45 years ago, these small positive-sense RNA viruses remain critically understudied. These studies provide fundamental new research on astrovirus pathogenesis and disruption of the gut epithelium by induction of epithelial-mesenchymal transition (EMT) following astrovirus infection. Here we characterize HAstV-induced EMT as an upregulation of SNAI1 and VIM with a down regulation of CDH1 and OCLN, loss of cell-cell junctions most notably at 18 hours post-infection (hpi), and loss of cellular polarity by 24 hpi. While active transforming growth factor- (TGF-) increases during HAstV infection, inhibition of TGF- signaling does not hinder EMT induction. However, HAstV-induced EMT does require active viral replication. These are among the first studies describing the induction of EMT by a non-oncogenic virus and provides an exciting opportunity to understand EMT induction independent of cancer. Our findings likely extend beyond astrovirus to other viruses and may shed light on novel ways pathogens can circumvent the barriers meant to protect against them. Crossing these barriers can lead to systemic and even fatal infections. Astroviruses can be especially problematic in immunocompromised individuals and infants where the virus has been associated with necrotizing enterocolitis, severe and persistent diarrhea, and even encephalitis and meningitis. Using our novel tools and models, we demonstrate that the FDA-approved broad-spectrum anti-infective drug nitazoxanide (NTZ) blocks astrovirus replication in vitro with a 50% effective concentration (EC50) of approximately 1.47μM. It can be administered up to 8 hours post-infection and is effective against multiple human astrovirus serotypes including clinical isolates. Most importantly, NTZ reduces viral shed in vivo, exhibiting its potential as a future clinical therapeutic. Overall, these studies will further our understanding of astrovirus pathogenesis leading to the development of therapeutic options for vulnerable populations
Confronting Inequity: Social Justice Dialogue in a Health Science Library
Get PDFObjective: To demonstrate how a departmental social justice discussion group was successful in achieving its purpose in introducing and discussing health-related social justice narratives and perspectives with personal meaning to each department member.
Methods: In the aftermath George Floyd’s death, the Assistant Director of Research and Education Services at a health sciences library proposed devoting a portion of staff meetings to discuss issues in social justice and anti-racism. Each department member would generate a topic and organize readings or links to media in an internal LibGuide. Initially, there was a total of seven discussions, each lasting an average of twenty minutes. Each staff member described their motivation in selecting their topic and accompanying resources and led the subsequent discussion.
Results: Discussion topics included white fragility, racial disparities surrounding leg amputations of Black diabetes patients in Mississippi, transracial adoption, local food deserts, white privilege in medical school education, black transgender violence and discrimination, and pipeline institutional racism. The readings and discussions revealed marginalized group perceptions and reality are not necessarily willingly acknowledged or addressed by the privileged group. The topic of food deserts was identified for follow-up action because of the need in the residential area adjacent to the health sciences campus.
Conclusions: Participants felt the topics were timely, thought-provoking and useful in understanding current imbalances in social equity in health-related areas. Each department member could identify and share a social justice area of concern. Many of the topics are addressed in critical librarianship scholarship, and lessons from the discussions could be applied to increased understanding of, and service to, marginalized users of their library’s community. Team members agreed to continue the discussions at staff meetings once per month on broader diversity and social justice topics
Building Community Through Programming with NLM Traveling Exhibits
Get PDFObjective: To demonstrate how programming around NLM’s traveling exhibit program can be used to connect and engage with communities outside the medical library.
Methods: The Quillen College of Medicine library hosted NLM’s “From DNA to Beer” and “Graphic Medicine: Ill-Conceived and Well-Drawn” exhibits and developed programming engaging with the university’s arts community, numerous locally owned businesses, and the local agricultural extension office.
Results: Exhibit planning was conducted with community engagement as a chief goal. Events included tours and talks at local craft breweries, trivia night at a downtown brewery, a bread-making workshop from extension agents, a presentation from a visiting national printmaking artist known for work about HIV/AIDS, and movie nights. Events were promoted via the web/social media, local news, and flyers placed at event sites and local comics shops. The planning and hosting of events at local businesses fostered town-gown connections, while arts talks engaged members of the university’s arts community who had not normally intersected with the medical library. Cooperation around complementary arts events also helped strengthen a connection with the university’s main visual arts museum. Overall, more than a thousand people engaged with the exhibits and surrounding programs and events.
Conclusions: Creative planning around NLM traveling exhibits can help forge new relationships with non-traditional partners throughout the community. Concrete examples of engaging events will be provided along with advice for focusing the exhibit planning process on community engagement
Library engagement in exploring stories of polio survivors in North Central Florida
Get PDFIntroduction/background: This project seeks to record stories of individuals who survived polio in the 1940s and 1950s in order to capture a unique moment in history, both in how polio impacted society- uniquely and similar to other disease outbreaks, and how individuals with polio negotiated their polio identity and told their story (or remembered through stories told by others).
For the former, infectious diseases can have a tremendous impact on culture, psychology, and the physical structure of society during the course of outbreaks and epidemics. Indeed the form of response often is similar from outbreak to outbreak, as people respond with fear to drastic and devastating changes to the social fabric. Much of this impact, however, can quickly be lost when the epidemic is over and life returns to normal. Even if it is a new normal, the response is to find stability and stories of life with the threat of disease fade from public consciousness. The concerns are that lessons are never remembered and the fear and panic from past epidemics can be repeated. This Polio story project aims to capture the experience of individuals and a society of a lost time, when polio instilled fear in families every summer in the early to mid-20th century. The story is unique in some ways to the biology of polio and the culture of the time, but also part of an old story of human fear and panic.
In addition, stories of people who survived polio lived through the collective experience and confronted the life changes that polio caused for them. Telling their story provided an opportunity to take control of who they were or who they became, and to write and rewrite stories of trauma. For many polio survivors, that story also involved navigating a world of physical barriers and advocating for inclusion and accessibility.
Objectives: The project represents a library outreach role in developing projects that capture history through oral history, recording stories of illness- in this case, polio. The UF Health Science Center Library historian worked with a Post Polio group in North Central Florida to connect with polio survivors and develop a collection of stories of personal experience, transcribed by the Samuel Proctor Oral History Program. These stories will become part of the University of Florida’s Digital Collection on the Proctor Oral History Program site, and made available through the UFDC webpage. The library’s engagement in the project also includes publication of a unique manuscript, through the UF Library Press and promotion of a video oral history, with plans to find funding for more videos.
Methods: This presentation discusses a UF library outreach project to capture stories of polio from people who were children in the 1940s and 1950s, and it includes conducting oral histories, preserving those stories and making them accessible, and working to publish manuscript material capturing experiences with polio. Oral history interviews were and still are being scheduled and recorded. The Smathers Libraries at the University of Florida, through a publication decision made by the UF Library Press, also published the daily journal kept by Lassie Goodbread Black, mother of polio survivor Edna Black Hindson that detailed Edna’s daily experiences as she recovered and lived with outcomes of paralytic polio.
Results: The efforts to create a polio oral history project at the University of Florida, includes identifying interested individuals, conducting interviews, transcribing materials, creating long term storage for the collection, finding other means to highlight stories and provide materials for understanding the impact of polio and other infectious diseases. The published book of Enda Black Hindson’s experience with polio is available as a pdf at https://ufdc.ufl.edu/AA00069222/00001 A print copy of the book can be purchased at https://upf.com/book.asp?id=9781944455095 . A video interview with polio survivor, author, former NPR commentator and publisher, Shelley Fraser Mickle can be found at https://www.youtube.com/watch?v=Nfy4XUTW9SU Transcripts of other interviews will be posted to the UFDC as they become available and as more interviews are completed.
Conclusions: Polio certainly impacted thousands when it was epidemic in the United States. An estimated 35,000 people were paralyzed each year in the 1940s. In 1952, an estimated 60,000 were infected, with more than 3,000 deaths. In terms of sheer numbers, it affected fewer people than tuberculosis or cancer. In terms of the fear it created, and the impact it had on society, it was unprecedented. Although adults could be affected, the fact that it struck many children, leaving those who survived paralyzed to a greater or lesser degree, mobilized the nation, leading to publicly funded research initiatives, and an invigorated movement to provide equal rights and access for those with disabilities. Caring for survivors impacted society; but survivors themselves worked to transform their world- leaving stories of struggle and triumph. The story of Edna Hindson’s experience, told in a unique way, helps to bring back an understanding of the disease’s impact. Infectious disease outbreaks have shaped human history, just as those impacts, or at least the psychological impacts of living with fear and uncertainty of disease spread are quickly forgotten. This project highlights the impact of one particular disease, polio, in the South through the words of survivors. The role and neutrality of a library facilitate outreach and connection with individuals who wish to share their stories
Increasing Nurse Knowledge Using a Formal Lung Transplant Education Program
Get PDFThis quality improvement project was completed to show that a formal lung transplant education course for nurses caring for lung transplant patients increased their knowledge. An eight-hour education course was developed by experts in the field of lung transplantation. A pretest was administered before the education course. A posttest was administered to determine if knowledge was improved. A three-month follow-up test was administered to determine knowledge retention. Based on the data analysis, nurse knowledge improved after formal education. Item analysis determined what areas of educational content need to be the focus of quarterly education. The education course was adopted as formal training for transplant nurses
Development of Novel Therapeutic Strategies for Pancreatic Cancer Treatment
Get PDFPancreatic cancer (PanCa) is the third deadliest cancer in the USA due to the late diagnosis and development of chemo-resistance, with a 5-year survival rate of less than 10%. The prognosis of patients with pancreatic ductal adenocarcinoma is extremely poor, and current therapies such as Gemcitabine, 5-FU, Nab-paclitaxel and, FOLFIRINOX alone or in combination, have displayed improved but marginal survival rates for patients. Therefore, research efforts are underway to discover new therapeutic options to treat PanCa and overcome resistance to available therapies.
Mucin, MUC13 is transmembrane glycoprotein, which is aberrantly overexpressed in PanCa and promoting cancer growth. Structural domains of MUC13, lead to oncogenic characteristics during cancer progression. Our lab previously established the role of MUC13 in tumor progression and metastasis by alteration of signaling pathways. Recent observations suggest the role of MUC13 in drug resistance and apoptosis in several cancer types. Therefore, it is of great interest to explore the role of MUC13 in chemoresistance in PanCa. Unlike other cancer types, PanCa is highly resistant to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) that emerges as one of the most-promising cancer therapeutic drugs. It is a death ligand that can selectively induce apoptosis in cancer cells over normal cells. Our recent work has demonstrated that MUC13 expressing cells showed resistance to TRAIL induced cell death and MUC13 knockdown leads to TRAIL sensitivity in cells. We have also observed that MUC13 expression blocks the activation of caspase-8 and Bid in PanCa cells in response to TRAIL treatment. Further investigation showed that alpha and beta domains of MUC13 are indispensable for blocking caspase-8 activation and PARP cleavage, indicating that the MUC13 blocks TRAIL-induced signaling upstream to Bid by inhibiting caspase-8 activation. Current studies revealed a new role of MUC13 ininhibiting TRAIL mediated activation of extrinsic apoptotic pathway in pancreatic cancer.
MicroRNAs (miRNA) have been identified as attractive targets for therapeutic intervention. The functional significance of lost miRNAs have been reported in several human malignancies, including PanCa. Restitution of lost miRNA function can provide a potential therapeutic benefit. Prior work has identified microRNA-145 (miR-145) as a tumor suppressor miRNA in PanCa. The restoration of miR-145 downregulates a number of oncogenes including mucin MUC13 and efficiently inhibits tumor growth in mice. Inhibition of MUC13 using miR-145 restoration resulted in TRAIL mediated increase in apoptotic cell death as evidenced by sub-G0 population and inhibition of MUC13, activation of caspase 8 and, cleavage of PARP-1. MiR-145 replacement can sensitize TRAIL therapy and counteract chemoresistance mechanism in PanCa.
The main challenge for successful translation of miRNAs into clinical practice remains an effective in vivo delivery system. Hence, the focus of this study was to develop and assess the efficacy of a miR-145 based nanoparticle formulation for PanCa treatment. Magnetic nanoparticle (MNP) based nanoformulation of miR-145 (miR-145-MNPF) was developed for the intracellular delivery and sustained release of miR-145. The positively charged polyethyleneimine molecules were used to increase the loading efficiency of miR-145. Treatment of cells with miR-145-MNPF led to efficient intracellular delivery of miR-145 mimics as observed through Prussian blue staining. This led to the simultaneous upregulation of miR-145 levels in cells which resulted in significant downregulation of target oncogenes including MUC13, HER2, pAKT and p53. miR-145-MNPF efficiently restores miR-145 in PanCa cells and inhibits growth and invasion of PanCa. miR-145 restitution using miR-145-MNPF may offer a potential therapeutic strategy for pancreatic cancer.
As discussed earlier that miR-145 restoration sensitized the TRAIL therapy in PanCa cells. Herein, we demonstrate the integration of novel delivery approach to reduce the delivery challenge of TRAIL. We have engineered unique superparamagnetic nanoparticles (MNPs) for co-delivering miR-145 and plasmid TRAIL for improving TRAIL response in PanCa model. MNP-miR-145-TRAIL nanoparticles were codelivered miR-145 and TRAIL to PanCa cells, which resulted in simultaneous restoration of miR-145 and inhibition of acquired resistance to TRAIL.
The current study demonstrates that acquired resistance to TRAIL in PanCa cells can be minimized with the replenishment of miR-145 expression. Combined actions of miR-145 and TRAIL markedly improve TRAIL-induced apoptotic effects in PanCa cells through the activation of an extrinsic apoptosis pathway as indicated by activation of DR4, FLIP, FADD and enhanced expression of cleaved caspase-8. The co-delivery of miR-145 and TRAIL using MNP nanoparticles inhibited tumorigenic characteristics of PanCa cells. The results were reciprocated and were further confirmed with the inhibition of tumorsphere formation and in vivo tumorigenicity in xenograft mice. Immunohistochemical staining of excised tumor tissues demonstrates an activation of the death receptor pathway and subsequent expression of apoptotic markers.
Pancreatic tumor microenvironment is a complex dynamic space which leads to desmoplasia and involved in metastasis and impediments against intracellular drug delivery. Despite extensive research efforts, there is not considerable progress in cancer therapeutics due to genomic complexity and heterogenicity of pancreatic cancer. Modern tumor therapy must be patient specific and customized for individual patients. It should be tailored for a patient-based response to the specific treatment. Thus, novel delivery vehicles are required that are biocompatible and non-immunogenic. This is possible by utilizing an autologous biological material as delivery vehicles that can be applied as a personalized medicine. Towards this, our lab has optimized an exosome based therapeutic approach, which utilizes exosomes isolated from the cultured tumor adjacent normal (NAT) fibroblast cells. We utilized this scaffold for safe and effective delivery of therapeutic payload. Our results demonstrated that NAT derived exosomal formulation (Exo-ORM) significantly enhanced the efficacy of ormeloxifene to inhibit stroma as indicated by decreased expression of α-SMA, desmin and hyaluronic acid. Exo-ORM formulation effectively inhibit EMT/SHH signaling in PanCa cells and in vivo models. NAT derived exosomes will be a promising therapeutic carrier with preferential size for passive targeting, proficient biophysical characteristics, biocompatible and nonimmunogenic vehicle for PanCa therapy
Black Women Survive Breast Cancer with Community-Based Care
Get PDFPURPOSE Community-based breast cancer support agencies who address non-medical, social determinants of health needs that serve as barriers to maximizing breast health outcomes may play a vital role in mitigating breast cancer mortality. They share a common emphasis on addressing social, economic, and psychological needs of breast cancer survivors and those at risk of breast cancer. This paper is third in a series of papers exploring why the rate of breast cancer mortality is two times higher for African American women than white women in Memphis. We sought insights from community-based breast cancer support agencies because they have a close-up view of circumstances and decision-making among women at risk of and surviving breast cancer, and a close view of primary care, surgical, and insurance environments impacting these women.
METHODS For this qualitative descriptive research study, data were collected using semi-structured in-depth focus groups with five breast cancer support agencies in Memphis. Categories and patterns were established using thematic analysis and a deductive a priori template of codes. RESULTS The main themes identified within support agencies were barriers to the use of services, education, health system support, and emotional support. Numerous sub themes included medication costs, support group supplemental programming, eligibility for mobile services, patient/provider communication, optimism, and family advice. Procrastinating, fearfulness, insurance, childcare, and transportation were barriers to care. Support agencies noted that one unique barrier that African American women who live in underserved areas of Memphis face in maintaining breast health is poor physician’s office management; in fragmented health care systems, information and patients can be lost to follow-up.
DISCUSSION/CONCLUSIONS Community-based breast cancer support agencies, who focus on social determinants of health, play a critical role as connectors for women with breast cancer who live in medically underserved areas and must find their way within a fragmented medical system.
GRANT SUPPORT This research was funded by the Tennessee Department of Health, grant number A17-1251
Characterization of Novel CB2 Agonist SMM-295 and Its Effects in Ischemia/Reperfusion Injury
Get PDFAcute kidney injury (AKI) is a major problem clinically affecting up to two-thirds of intensive care unit patients, and results in increased hospitalization time, the risk of developing chronic kidney disease, and mortality. Hallmarks of AKI include tubular cell death and a decrease in renal perfusion which leads to decreases in renal function following injury. For 20 years the pathophysiology of AKI has been well established. However, therapies for AKI have shown minimal to no success clinically. The work here describes our efforts to further categorize the effects of CB2 activation, a possible novel therapeutic target in AKI.
There is increasing importance associated with the understanding of the biological activity of the cannabinoid receptors following the increased acceptance in the medicinal purposes of cannabis and cannabis-related compounds. The endocannabinoid system is comprised of its cognate G-protein coupled receptors, cannabinoid type 1 and 2 receptors, endogenous lipid signaling molecules, N-arachidonoyl ethanolamine (AEA) and 2-acylglycerol, and the enzymes involved in their biosynthesis and catabolism. In the kidney, the CB1 receptors consistently demonstrate deleterious effects on glomerular and tubular function in various acute and chronic forms of injury, while CB2 receptors have demonstrated the opposite effects.
This work will demonstrate the findings of studies that focus on the role of CB2 in the recovery from ischemia/reperfusion injury (IRI) and the effects of CB2 activation on both tubular cell death and renal hemodynamics. To study the effect of CB2 activation on renal damage following IRI, our scientific group tested a small molecule agonist, SMM-295 [3′-methyl-4-(2-(thiophen-2-yl) propan-2-yl) biphenyl-2,6-diol], in an investigation of the CB2 receptor as a potential therapeutic target in the prevention of tubular epithelial cell damage after AKI. To test this compound in AKI, we used a mouse model of renal bilateral ischemia-reperfusion injury (IRI), which is a common experimental model to study AKI, demonstrating considerable beneficial effects of SMM-295 following injury. Subsequently, we then investigated the possible mechanisms that undermine the effects of SMM-295, including initiation of antiapoptotic signaling cascades in tubular epithelium as well as increases in renal perfusion through a vascular effect demonstrating a multifunctional role for SMM-295 in the treatment of IRI.
Our findings demonstrate that CB2 activation by SMM-295 ameliorated the effects of IRI through decreased tubular cell death in proximal tubule cells along with an increase in renal perfusion through a direct vascular effect. These data indicate selective activation of the CB2 receptor by our novel CB2 agonist SMM-295 has therapeutic value in pre-clinical studies and may provide a new target for therapy in the treatment of AKI