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Item Open Access Quality-of-life impact of interstitial cystitis and other pelvic pain syndromes(2023-05-25) Cunningham, Andrew R.; Gu, Lin; Dubinskaya, Alexandra; De Hoedt, Amanda M.; Barbour, Kamil E.; Kim, Jayoung; Freedland, Stephen J.; Anger, Jennifer T.Objective: To compare health-related quality of life (HRQOL) and pelvic pain levels over time in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) and those with other pelvic pain conditions (OPPC) including chronic prostatitis, dyspareunia, vaginismus, vulvodynia, and vulvar vestibulitis. Methods: We prospectively enrolled male and female patients from any Veterans Health Administration (VHA) center in the US. They completed the Genitourinary Pain Index (GUPI) quantifying urologic HRQOL and the 12-Item Short Form Survey version 2 (SF-12) quantifying general HRQOL at enrollment and 1 year later. Participants were classified by ICD diagnosis codes and confirmed by chart review to be IC/BPS or OPPC (308 and 85 patients respectively). Results: At baseline and follow-up, IC/BPS patients, on average, had worse urologic and general HRQOL than OPPC patients. IC/BPS patients demonstrated improvement in urologic HRQOL measures over the study but demonstrated no significant change in any general HRQOL measure suggesting a condition-specific impact. Patients with OPPC demonstrated similar improvements in urologic HRQOL but had deteriorating mental health and general HRQOL at follow-up suggesting a wider general HRQOL impact for these diseases. Conclusions: We found that patients with IC/BPS had worse urologic HRQOL compared to other pelvic conditions. Despite this, IC/BPS showed stable general HRQOL over time, suggesting a more condition-specific impact on HRQOL. OPPC patients showed deteriorating general HRQOL, suggesting more widespread pain symptoms in these conditions.Item Open Access The Use of Teledentistry in Clinical Oral and Maxillofacial Pathology Practice: An Institutional Experience(2023-07-20) Flores-Hidalgo, Andres; Collie, John; King, Shae; Grant, Ford T.; Beasley, Nicole E.; Moss, Mark E.; Tempel, Thomas R. Jr.Background: Although there has been a slight increase in dental professionals since 2011, 98 of North Carolina's 100 counties are designated as Dental Health Professional Shortage Areas by the Heath Resources and Service Administration. This shortage significantly increases disparities and access to primary and specialized oral health care. Also, dental professionals in these remote locations may feel the access and referrals to oral and maxillofacial pathologists cumbersome. In 2020, the COVID-19 pandemic prompted an inevitable surge in the use of digital technology due to the social distancing norms and lockdowns, which forced dental education institutions and practitioners to adjust to new ways of meeting, teaching, and providing dental care. In the present manuscript, we report our institutional experience delivering specialized dental care in rural areas. Materials and methods: We conducted a retrospective case series of diagnosis, management, and outcomes of patients who underwent synchronous or asynchronous virtual and remote examination of oral lesions at ECU School of Dental Medicine and one satellite clinic over seven years. For those cases that concluded on surgical sampling, the clinical impressions, differential diagnoses, and the final diagnosis were compared to assess the accuracy of the clinical exam through teledentistry. Results: The total study population consisted of 71 patients. Most of the remote consultations were done asynchronously. Also, most virtual clinical consultations were initiated due to clinical suspicion of malignancy and infectious/reactive conditions, accounting for 42% and 25.3% of all encounters. Conclusions: The presented data suggest how teledentistry can support clinical practice in rural areas to achieve optimal care for the patient in rural or remote communities. Also, it significantly decreases the travel required, the number of appointments, and increases the speed of diagnosis. Teledentistry is an excellent tool available to all clinicians and can dramatically aid in diagnosing oral mucosa lesions.Item Open Access Subtle alterations of vestibulomotor functioning in conductive hearing loss(2023-08-29) Manno, Francis A. M.; Cheung, Pikting; Basnet, Vardhan; Khan, Muhammad Shehzad; Mao, Yuqi; Pan, Leilei; Ma, Victor; Cho, William C.; Tian, Shile; An, Ziqi; Feng, Yanqiu; Cai, Yi-Ling; Pienkowski, Martin; Lau, CondonIntroduction: Conductive hearing loss (CHL) attenuates the ability to transmit air conducted sounds to the ear. In humans, severe hearing loss is often accompanied by alterations to other neural systems, such as the vestibular system; however, the inter-relations are not well understood. The overall goal of this study was to assess vestibular-related functioning proxies in a rat CHL model. Methods: Male Sprague–Dawley rats (N=134, 250g, 2months old) were used in a CHL model which produced a >20dB threshold shift induced by tympanic membrane puncture. Auditory brainstem response (ABRs) recordings were used to determine threshold depth at different times before and after CHL. ABR threshold depths were assessed both manually and by an automated ABR machine learning algorithm. Vestibular-related functioning proxy assessment was performed using the rotarod, balance beam, elevator vertical motion (EVM) and Ferris-wheel rotation (FWR) assays. Results: The Pre-CHL (control) threshold depth was 27.92dB±11.58dB compared to the Post-CHL threshold depth of 50.69dB±13.98dB (mean±SD) across the frequencies tested. The automated ABR machine learning algorithm determined the following threshold depths: Pre-CHL=24.3dB, Post-CHL same day=56dB, Post-CHL 7 days=41.16dB, and Post-CHL 1 month=32.5dB across the frequencies assessed (1, 2, 4, 8, 16, and 32kHz). Rotarod assessment of motor function was not significantly different between pre and post-CHL (~1week) rats for time duration (sec) or speed (RPM), albeit the former had a small effect size difference. Balance beam time to transverse was significantly longer for post-CHL rats, likely indicating a change in motor coordination. Further, failure to cross was only noted for CHL rats. The defection count was significantly reduced for CHL rats compared to control rats following FWR, but not EVM. The total distance traveled during open-field examination after EVM was significantly different between control and CHL rats, but not for FWR. The EVM is associated with linear acceleration (acting in the vertical plane: up-down) stimulating the saccule, while the FWR is associated with angular acceleration (centrifugal rotation about a circular axis) stimulating both otolith organs and semicircular canals; therefore, the difference in results could reflect the specific vestibular-organ functional role. Discussion: Less movement (EVM) and increase time to transverse (balance beam) may be associated with anxiety and alterations to defecation patterns (FWR) may result from autonomic disturbances due to the impact of hearing loss. In this regard, vestibulomotor deficits resulting in changes in balance and motion could be attributed to comodulation of auditory and vestibular functioning. Future studies should manipulate vestibular functioning directly in rats with CHL.Item Open Access m6A Regulates Breast Cancer Proliferation and Migration through Stage-dependent Changes in Epithelial to Mesenchymal Transition Gene Expression(2023-11-07) Dorgham, Mohammed G.; Elliott, Brittany A.; Holley, Christopher L.; Mansfield, Kyle D.While many factors have been implicated in breast cancer progression, effective treatments are still lacking. In recent years, it has become clear that posttranscriptional regulation plays a key role in the aberrant gene expression underlying malignancy and metastasis. For example, the mRNA modification N6-methyladenosine (m6A) is involved in numerous post-transcriptional regulation processes and has been implicated in many cancer types, including breast cancer. Despite intense study, even within a single type of cancer, there is little consensus, and often conflicting results, as to the role of m6A, suggesting other factors must influence the process. The goal of this study was to determine if the effects of m6A manipulation on proliferation and migration differed based on the stage of disease progression. Using the MCF10 model of breast cancer, we reduced m6A levels by targeting METTL3, the main cellular m6A RNA methyltransferase. Knocking down Mettl3 at different stages of breast cancer progression indeed shows unique effects at each stage. The early-stage breast cancer line showed a more proliferative phenotype with the knockdown of Mettl3 while the transformed breast cancer line showed a more migratory phenotype. Interestingly, the metastasized breast cancer cell line showed almost no effect on phenotype with the knockdown of Mettl3. Furthermore, transcriptome wide analysis revealed EMT as the probable pathway influencing the phenotypic changes. The results of this study may begin to address the controversy of m6A’s role in cancer and suggest that m6A may have a dynamic role in cancer that depends on the stage of progression.Item Open Access A SEER Database Retrospective Cohort of 547 Patients with Penile Non-Squamous Cell Carcinoma: Demographics, Clinical Characteristics, and Outcomes(2023-10-31) Ashley, Lucas W.; Sutton, Kent F.; Ju, Andrew; Edwards, George; Pasli, Melisa; Bhatt, ArjunIntroduction: Little research has investigated the prevalence and distribution of the diverse pathologies of non-squamous cell carcinoma (non-SCC) of the penis. Although rare in clinical practice, these cancers have become a focus of greater importance among patients, clinicians, and researchers, particularly in developing countries. The principal objective of this study was to analyze the major types of penile non-SCC, elucidate common treatment pathways, and highlight outcomes including 5-year survival. Materials/methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried between 2000 and 2018 to identify a retrospective cohort of patients with penile non-SCC. Demographic information, cancer characteristics, diagnostic methods, treatments administered, and survival were investigated. Results: A total of 547 cases of penile non-SCC were included in the analysis. The most prevalent non-SCC cancers included epithelial neoplasms, not otherwise specified (NOS) (15.4%), unspecified neoplasms (15.2%), basal cell neoplasms (13.9%), blood vessel tumors (13.0%), nevi and melanomas (11.7%), and ductal and lobular neoplasms (9.9%). Over half (56.7%) of patients elected to undergo surgical intervention. Patients rarely received systemic therapy (3.8%) or radiation (4.0%). Five-year survival was 35.5%. Patients who underwent surgery had greater annual survival for 0–10 years compared to those who did not have surgery. Significant differences in survival were found between patients who had regional, localized, and distant metastases (p < 0.05). A significant difference in survival was found for patients married at diagnosis versus those who were unmarried at diagnosis (p < 0.05). Lower survival rates were observed for patients older than 70 years. Discussion: Although less prevalent than SCC, penile non-SCC encompasses a diverse set of neoplasms. Patients in this cohort had a high utilization of surgical management leading to superior outcomes compared to those not receiving surgery. Radiation is an uncommonly pursued treatment pathway. Patient demographics and socioeconomic variables such as marital status may be valuable when investigating cancer outcomes. This updated database analysis can help inform diagnosis, management, and clinical outcomes for this rare group of malignancies.Item Open Access A closer look to neural pathways and psychopharmacology of obsessive compulsive disorder(2023-11-17) Gargano, Steven P.; Santos, Melody G.; Taylor, Sydney M.; Pastis, IreneThe intricate neural pathways involved in obsessive-compulsive disorder (OCD) affect areas of our brain that control executive functioning, organization, and planning. OCD is a chronic condition that can be debilitating, afflicting millions of people worldwide. The lifetime prevalence of OCD in the US is 2.3%. OCD is predominantly characterized by obsessions consisting of intrusive and unwanted thoughts, often with impulses that are strongly associated with anxiety. Compulsions with OCD encompass repetitive behaviors or mental acts to satisfy their afflicted obsessions or impulses. While these factors can be unique to each individual, it has been widely established that the etiology of OCD is complex as it relates to neuronal pathways, psychopharmacology, and brain chemistry involved and warrants further exploration.Item Open Access Similarities and Differences Regarding Acute Anorexia Nervosa and Semi-starvation: Does Behavioral Thermoregulation Play a Central Role?"(2023-10-25) Smith, Lucille LakierObjective: To clarify the association between acute anorexia nervosa (AN) and semi-starvation (SS) by focusing on similarities and differences in physiology, mood, and behavior. Method: A comparison of published literature between these two groups. Results: Both groups show similar hormonal and metabolic changes in response to caloric restriction and extreme weight loss (~25%). Associated changes result in a reduced body temperature (Tcore-low). Maintenance of body temperature within a specific range is crucial to survival. However, both groups cannot activate autonomic strategies to maintain their Tcore-low, such as increasing metabolic rate, constricting skin blood vessels, or shivering. Furthermore, Tcore-low increases the individuals’ “coldness sensations” throughout the body, hence the frequent reports from ANs and SSs of “feeling cold.” To eliminate these uncomfortable “coldness sensations” and, importantly, to maintain Tcore-low, ANs, and SSs “select” different thermoregulatory behavioral strategies. It is proposed that the primary differences between AN and SS, based on genetics, now manifest due to the “selection” of different thermo-regulatory behaviors. AN patients (ANs) “select” hyperactive behavior (HyAc), which increases internal metabolic heat and thus assists with maintaining Tcore-low; in harmony with hyperactive behavior is a lively mood. Also related to this elevated arousal pattern, ANs experience disrupted sleep. In contrast, SS individuals “select” a passive thermo-behavioral strategy, “shallow torpor,” which includes reduced activity, resulting in energy conservation. In addition, this inactivity aids in the retention of generated metabolic heat. Corresponding to this lethargic behavior, SS individuals display a listless mood and increased sleep. Conclusion: Initial similarities between the two are attributable to physiological changes related to extreme weight loss. Differences are most likely attributable to genetically programmed “selection” of alternate thermoregulatory strategies, primarily to maintain Tcore-low. However, if acute AN is prolonged and evolves into a chronic condition, AN will more closely align with starvation and more precisely reflect SS symptomology.Item Open Access Challenges and Instructor Strategies for Transitioning to Online Learning During and After the COVID-19 Pandemic: A Review of Literature(2023-09-13) Richards, Keith; Thompson, Brittany Myles WrightThe COVID-19 pandemic triggered an unprecedented shift to online learning, significantly impacting the higher education landscape. This paper examines the challenges faced by faculty and students during the rapid transition to online instruction and explores best practices for delivering effective online courses. The increased adoption of online learning created stress for faculty and resulted in academic setbacks for students. Although challenges are present strategies exist to help faculty create rich online learning environments. One important element is engagement, which looks at both student engagement with the material and with their classmates and faculty. In addition to working on student engagement the faculty were now in a position that required a new type of expertise to manage online interactions, which can be much different from their experiences in traditional classrooms. Insufficient time for proper course adaptation and limited knowledge of online teaching methods added to these challenges. Effective online delivery requires careful planning, utilization of advanced instructional technologies, and creating an immersive and interactive learning environment. Faculty must also adapt their teaching strategies to accommodate the unique challenges of online instruction. This review highlights the significance of a quality learning management system (LMS) as the backbone of online courses. An effective LMS facilitates course management, content delivery, and student interaction. Future considerations include providing comprehensive faculty support and training, promoting effective communication and collaboration among students, and incorporating interactive elements into online lessons. The following will provide lessons learned from the COVID-19 pandemic which will help faculty to improve their instructional competence and social presence in the online classroom.Item Open Access User centric metrics for a realistic assessment of broadband services(2023-10-11) Popoviciu, CiprianPast broadband adoption initiatives underscored common wisdom: “We cannot manage what we cannot accurately measure”, “Trust but verify”. Self-reported Federal Communications Commission data has been notoriously unreliable or lacking granularity and that led to an overoptimistic perception of the quality and coverage of broadband services. Data collected in the past was deficient in providing a complete view of the user experience by focusing exclusively on a simple metric, bandwidth availability. Moreover, data collected in the past typically provided a point-in-time perspective on the state of broadband services in each region. In this paper, we discuss a new set of metrics and measurement techniques needed to make broadband funding decisions efficient in terms of quality of services delivered and return on investment, and to track their progress. We propose composite metrics that capture the complete value of the service to the user and emphasize the feasibility of measuring and monitoring such a metric over time.Item Open Access Apoptosis mechanisms induced by 15d-PMJ2 in HCT116 colon cancer cells: insights into CHOP10/TRB3/Akt signaling(2023-11-02) Albassam, Hussam; Ladin, Daniel A.; Elhassanny, Ahmed; Burns, ColinAgents that stimulate the endoplasmic reticulum (ER) stress pathway are being exploited pharmacologically to induce cancer cell death. Cytotoxic ER stress is typically regulated by the transcription factor, C/EBP homologous protein 10 (CHOP10). Products of CHOP10 transcription include the pro-apoptotic proteins: ER oxidoreductase 1α (ERO1α), death receptor-5 (DR5), and tribbles-related protein 3 (TRB3). Our previous findings showed cell death induced by 15-deoxy- Δ12,14 prostamide J2 (15d-PMJ2) occurred in an ER stress-dependent manner. However, the pathway by which 15d-PMJ2 regulates ER stress-mediated death downstream of CHOP10 has not been identified. Our results demonstrate 5 µM 15d-PMJ2 increased CHOP10 expression and apoptosis in HCT116 colon cancer cells. In cells treated with pharmacological inhibitors of ER stress, 15d-PMJ2-induced apoptosis was reliant upon the ER stress pathway. To investigate the role of CHOP10 and its transcriptional products in apoptosis, genetic deletion of CHOP10 (CHOP10-KO) was performed using the CRISPR/Cas9 system. The apoptotic action of 15d-PMJ2 was blunted in cells lacking CHOP10 expression. The deletion of CHOP10 reduced the expression of DR5, ERO1α, and TRB3 although only the expression of TRB3 was significantly reduced. Therefore, we overexpressed TRB3 in CHOP10-KO cells and observed that the activation of Akt was inhibited and 15d-PMJ2-induced apoptosis was restored. Thus, a mechanism of apoptosis elicited by 15d-PMJ2 includes the stimulation of CHOP10/TRB3/Akt inhibition. Given the important role these signaling molecules play in cancer cell fate, 15d-PMJ2 may be an effective inducer of apoptosis in cancer cells.Item Open Access How do we best support adolescents with low academic performance and learning disabilities in the era of pandemic learning loss? The importance of intensive learning strategy interventions(2023-11-02) O'Brien, Chris; Boudah, Daniel J.; Lopuch, Jeremy; Nance, AaronThe COVID-19 pandemic put a spotlight on learning loss that teachers of low-performing adolescents, including those with learning disabilities (LD), have confronted for decades. Federal funding offers opportunities for school districts across the country to implement evidence-based interventions that promote outcomes for students with learning difficulties in middle and high schools including those from culturally and linguistically diverse backgrounds. There is a risk, however, of funding weak models of tutoring that prioritize subject-specific “homework help” in contrast to more effective programs. Research directs schools to the use of coherent intervention programs which are built into the school day, integrated into IEPs, facilitated by competent educators, employ a model of explicit-intensive instruction that has the most significant impact on learning outcomes for students with learning difficulties, and prioritize strategies that generalize to multiple content areas. Recommendations are presented for developing Individualized Education Programs for adolescents with LD, which align with the need for challenging, ambitious goals and special education services that are based on an extensive body of research.