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Changes In Metabotropic Glutamate Receptor Trafficking During Protracted Ethanol Withdrawal
Abstract
As a result of chronic ethanol exposure, the brain undergoes neuroadaptive changes as a response to glutamatergic dysregulation. In this study, quantified the expression of group I metabotropic glutamate receptors (mGlu1 and mGlu5), during withdrawal from chronic intermittent ethanol exposure. In addition, we also quantified known trafficking/anchoring partners, including Homer proteins. This quantification was conducted using western blot analysis on whole tissue lysate as well as after a biotin labeling of surface (membrane bound) proteins in withdrawal and control rats. Our exposure paradigm consists of rats being exposed to volatilized ethanol vapor pumped into a sealed chamber for four consecutive days, followed by a three-day withdrawal. This cycle continued for three weeks after which the rats are placed into forced withdrawal withdraw for 35 or 55 days. Tissue from the basolateral amygdala (BLA) was then micro dissected for further processing and western blot analysis. Our results showed no significant changes in metabotropic glutamate receptor trafficking. However, we did notice Homer 1b/c significantly decreased in surface protein expression while Homer 2 was significantly increased in levels of surface protein expression. These data suggest differential trafficking of Homer and mGlu proteins that could differentially impact synaptic function during protracted withdrawal. Future studies will seek to measure the functional contribution of mGlu during protracted withdrawal
Association between state ICU bed utilization and income-based equality rankings during the 2020 COVID-19 surge
Abstract
The COVID-19 pandemic has strained healthcare systems in the United States, particularly hospital and ICU bed availability. We investigated the impact of income-based equality rankings on ICU bed utilization during the 2020 winter surge, hypothesizing the utilization of ICU beds is associated with the rankings of income-based equality among states. We conducted a cross-sectional study comparing different population-adjusted metrics of hospital bed and COVID-19 infection among three income-based equality state groups (upper-, middle-, and lower-rank). State-aggregated data of COVID-19 hospital cases was collected on November 29, 2020, and was further adjusted to the 2019 population data from the Census Bureau. The fifty states were grouped according to the income-based equality ranking. Mean values of the population-adjusted metrics of hospital bed and COVID-19 infection were compared among the groups with one-way ANOVA, followed by pairwise comparisons using the Tukey HSD procedure for multiple comparison adjustment. Log transformation was applied to the percent-based utilization data for better normal approximation. Low-rank states exhibited higher ICU bed utilization (9.4% increase, p=0.022) and staff shortage (12.8% increase, p=0.0013) compared to middle-rank states. Additionally, low-rank states had elevated COVID-19 inpatient bed utilization (16.4%) compared to upper- (10.5%, p=0.039) and middle-rank (11.9%, p=0.0064) states. Upper- and middle-rank states showed lower percentages of inpatients with COVID-19 infection (p=0.019, p=0.036). Our findings indicate states with higher income-based equality rankings performed significantly better regarding ICU bed utilization and staff shortages during the 2020 winter surge, emphasizing the need to address income-based disparities for improved healthcare delivery and emergency preparedness
The relationship of cervical range of motion and movement control with temporomandibular dysfunction: A pilot study
Abstract
Evidence exists that cervical posture is associated with temporomandibular joint dysfunction (TMD). Few studies have examined cervical spine active range of motion and cervical movement control in subjects with TMD. The purpose of this study is to pilot a protocol comparing cervical spine range of motion and cervical movement control between subjects with and without TMD.
Subjects include individuals 18-60 years of age with or without the presence of TMD signs/symptoms of jaw pain, limited jaw motion, or joint noise. Subjects exclude those with history of jaw or cervical spine surgery within 5 years, history of joint disease of the temporomandibular joint (TMJ) or cervical spine, cervical or TMD symptoms under active treatment by a healthcare provider, moderate or severe neck disability as identified by the Neck Disability Index (NDI), systemic disease impacting the cervical spine or TMJ, and subjects who are pregnant.
Data collection has been initiated and includes: TMJ Disability Index and NDI scores, active cervical range of motion for six physiologic motions, cervical movement control tests described by Patrocini et al. (2014), active maximal mouth opening and lateral deviation and TMD subgroup classification. Cervical movement control will be scored by a physical therapist with \u3e 10years of experience blinded to subject classification into the control or TMD groups. Tests specific to the TMJ will be completed by a physical therapist with \u3e 10 years of experience blinded to the cervical movement control scores
Systemic reaction to calcium phosphate after retrograde repair of a osteochodral lesion of the talus
Abstract
Introduction: Osteochondral lesions of the talus (OLT s is a common pathology involving hyaline cartilage and/or underlying bone. Surgical decision making of OLT repair is reliant on the location of the OLT and quality of the cartilage and the bone. Retrograde drilling of the subchondral bone is a common modality for repair of OLTs. This is a case report of a systemic reaction to the graft material during the immediate post operative after a retrograde drilling.
Case Report: A 34 year old female presented with chronic pain in the left ankle. Imaging revealed a posterior medial OLT. The patient agreed to and underwent an ankle arthroscopy with extensive debridement and a retrograde drilling of the OLT with with the use of 1.6cc of calcium phosphate to ‘ the retrograde drilling. Approximately 24 36 hours after the surgery, the patient presented to the emergency room with a fever of 101.6, chills, tachycardia and severe left ankle/lower leg pain. Exam of the left lower extremity showed no signs of any infective process. X rays of the left ankle showed a large amount of osseous appearing debris along the soft tissue plane of the ankle. The patient was diagnosed with a “fever of unknown origin” ( Serial radiographs during the post operative period has shown significant gradual decrease in the appearance osseous material at the 4 week, 8 week, and 12 weeks. The patient has not reported any additional fevers. She does report pain along the intermediate dorsal cutaneous nerve where some of the graft material continues to absorb
Use of hormonal contraception and risk of ACL injury in women
Abstract
Women are at greater risk for anterior cruciate ligament (ACL) injury than men. Several studies have suggested that hormonal fluctuations contribute significantly to this difference. We will summarize the literature to describe the effect of using hormonal contraceptives on the stability of the ACL joint in women. By providing a concise synthesis of available research, readers will be able to discern whether using hormonal birth control is a good option for females if they are concerned about risk of injuring their ACL. Review of articles including only reviews and randomized controlled trials published after 2017. Collectively, these data suggest that the use of hormonal contraceptives does provide a protective effect on the ACL for women, but further investigation is still warranted
Glutamate receptor dysregulation during protracted withdrawal from intermittent ethanol vapor in rats
Abstract
Functional dysregulation of glutamatergic receptor systems during withdrawal from chronic drug exposure is a primary driver of drug craving and subsequent resumption of drug use. Animal models (psychostimulants) have demonstrated dynamic alterations in both AMPA and NMDA receptor function and expression that contribute to drug seeking behavior. Regulation of these receptor systems can begin as early as a few days following cessation of drug use and are persistently expressed into long term withdrawal (\u3e60d). Short term withdrawal from chronic ethanol exposure induces functional dysregulation of AMPA and NMDA receptors suggesting that similar mechanisms may be regulated across drugs. To this end, we investigated AMPA and NMDA receptor mediated synaptic function during protracted withdrawal (\u3e35d) from chronic intermittent ethanol (CIE) exposure using whole cell patch clamp electrophysiology. We focused on the basolateral amygdala (BLA), as glutamatergic signaling in this region is robustly modulated by short term (24 h) withdrawal from CIE (and regulates anxiety like behavior expressed during withdrawal. Adolescent rats exposed to repeated cycles of CIE (12 hr/day, 4 d on/3 d off, 3 cycles) demonstrated significantly increased functional contributions of NMDA receptors in male but not female animals. TK30, a GluN3 antagonist and ifenprodil, a GluN2B antagonist significantly reduced responses in withdrawal but not control cells. In addition, we have measured an increased sensitivity to the GluA1 antagonist NASPM, suggesting an increased functional contribution of GluA1-containing AMPARs during protracted withdrawal. Our data support widespread dysregulation of glutamate signaling during protracted withdrawal from ethanol exposure
Oral Presentations
Various Clinical, Biomedical Science, and Public health oral presentations were given during this time
Artichoke: An Artist to Choke Cervical Cancer by Downregulation of Cyclin D and Bcl-2
Abstract
Background: Cervical cancer (CC) continues to be one of the leading causes of mortality worldwide. It is estimated that 90% of deaths from CC occur in low- and middle-income countries. Artichoke is a commonly consumed plant that has been studied more recently with increasing interest for its abundance in antioxidants. Our previous study showed that artichoke extract (AE) is a potent inhibitor of melanoma. To extend that study, this study is designed to assess the potential antitumor effects of AE on the SiHa CC cell line.
Methods: Clonogenic survival assay, cell proliferation, and caspase-3 activity kits were used to evaluate the effects of AE on cell survival, proliferation, and apoptosis of SiHa CC cells. Molecular mechanisms were further assessed by using RT-PCR and IHC.
Results: SiHa CC cell colony count significantly decreased in the presence of AE. A decrease in the OD value of CC cells was also found in the presence of AE. The relative caspase-3 activity in SiHa CC cells increased significantly in the presence of AE. The anti-proliferative effect of AE on SiHa CC cells correlated with decreased expression of cyclin D. The pro-apoptotic effect of AE on SiHa CC cells correlated with decreased expression of Bcl-2.
Conclusions: Artichoke inhibits growth of CC through inhibiting proliferation and promoting apoptosis by downregulation of cyclin D and Bcl-2. These findings extend the anti-tumor effect of artichoke from melanoma to CC, supporting the concept that artichoke exerts powerful anti-tumor property in not only one cancer. Such a study may be useful to develop natural treatments for many types of cancers
Isolation and characterization of three bacteriophages targeting Acinetobacter baumannii AB5075
Abstract
Acinetobacter baumannii is emerging as one of the most challenging bacterial pathogens to manage and treat in hospitals worldwide due to its increasing resistance to all currently available antibiotics. Acinetobacter baumannii accounts for 20% of infections across ICUs worldwide, with a mortality rate greater than 50%. Because of its threat to human health, A. baumannii is currently classified by the World Health Organization (WHO) as a critical priority pathogen for which new treatment options are urgently needed.
Using bacteriophages to treat bacterial infections, commonly called phage therapy, is gaining interest as a promising alternative treatment option for infections caused by antibiotic-resistant bacteria. However, there are currently only 184 bacteriophages targeting A. baumannii with genome sequences that are complete and publicly available. The goal of this research is to isolate and characterize lytic bacteriophages that target the model strain of A. baumannii called AB5075.
Three phages were successfully isolated from activated sludge obtained at the Des Moines Metropolitan Wastewater Reclamation Authority. Phage morphology was assessed using transmission electron microscopy. These phages have distinct dimensions, indicating that they are different phages. However, they each exhibit a myophage morphology, possessing icosahedral heads and contractile tails. In the near future, the host range, genome, and growth characteristics of these phages will be characterized.
Ultimately, this research aims to increase our knowledge of bacteriophages that target A. baumannii and add to a growing collection of phages for potential therapeutic use against this notoriously antibiotic-resistant pathogen
Examining Racial Disparities in Unemployment Among Health Care Workers Before, During, and After the COVID-19 Pandemic
Among the U.S. health care workforce, the COVID-19 pandemic appeared to greatly impact employment levels in 2020. However, no research has examined how the pandemic’s impact on employment varied by racial/ethnic group or beyond the initial emergency year. Our study aimed to quantitatively evaluate workforce trends by race/ethnicity before, during, and after the COVID-19 pandemic. This study analyzed each March supplement of the Current Population Survey over a 5-year span (2018–2022). We restricted the sample to nurses, physician assistants, and other non-physician health care workers (HCW), per specific census occupation codes, and constructed an event-history study to test for differential effects from each year, as compared to 2019, on the proportion of employment between non-Hispanic White, non-Hispanic Black, Hispanic, non-Hispanic Native (American Indian, Alaska Native, Hawaiian Islander), and non-Hispanic Asian HCW. Results suggest that the pandemic’s negative impact on the health care workforce disproportionately reduced employment for HCW self-identifying as Black or Indigenous. Rates for other groups increased 2–3 percentage points in 2020 but returned to prepandemic levels by 2022. However, for Black and Native HCW, the change was twice as large in 2021 and remained significantly higher in 2022 for Black HCW, providing more evidence that the burden of the COVID-19 pandemic disproportionately fell on people of color. Future research investigating how employment disruptions impacted the health care workforce and, potentially, health equity remains warranted