2022
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Item PKD1 Variants of Uncertain Significance Found in a 64 year-old Male With Simple Renal Cysts and Thoracic Aortic Disease(2022) Tatapudi, Suhas V.V.Introduction: Thoracic aortic disease (TAD) - aneurysms and dissections, is a clinically silent disorder caused by weakening of major blood vessels which may lead to rupture and imminent mortality. Simple renal cysts are relatively common and are associated with numerous etiologies. Case presentation: Here we present the case of a 64 year-old male with a history of smoking, hypertension, and stroke due to cerebral aneurysm. He presented with substernal chest pain and was diagnosed with a type B aortic dissection extending from the left subclavian artery to the left iliac artery. An aortic endograft was placed to prevent rupture, covering the ostium of the left subclavian artery. Immediate post-operative bilateral lower extremity paraplegia developed, ultimately necessitating a subclavian artery bypass for resolution. Despite clinical improvement, two weeks post-operatively an aortic rupture occurred, leading to cardiac arrest and demise. Pathologic and Ancillary findings: Notable findings on autopsy included aortic dissection and rupture, left hemothorax, multicystic kidneys, and prior evidence of craniotomy. The dissection extended anterograde to left internal iliac artery and retrograde to the sinotubular junction with rupture just distal to the distal aspect of the endograft. No abnormalities were reported in aortopathy panels. Polycystic kidney disease panels revealed three variants of uncertain significance (VUS) within the PKD1 gene: p.Val2905Ile, p.Lys3232Glu, p.Leu3477Ile. Congophilic (amyloid) angiopathy was discovered within several vessels in the brain which may be associated with the history of a cerebral aneurysm. Discussion: Hypertension and smoking are significant risk factors for systemic vascular disease. While PKD1 and PKD2 mutations can be seen associated with autosomal dominant polycystic kidney disease, heterozygous mutations may result in milder cystic disease. Through retrospective case reports and series, Ziganshin et al proposed an association between simple renal cysts and TAD. As more evidence is established, a diagnosis of simple renal cysts may prompt the need for screening for TAD. Our clinical and molecular picture may further substantiate a potential relationship between TAD, cystic renal disease, and mutations in PKD1 and PKD2 genes. Furthermore, genetic counseling may also be necessary for surviving family members. This case exemplifies the importance of postmortem autopsies and the discovery of genetic variants with potential clinical implication.Item A Giant Ovarian Mucinous Cystadenoma and Low-Grade Appendiceal Mucinous Neoplasm in a Post-Menopausal Woman(2022) Aguirre, Brian; Bartels, HollisBackground: Ovarian mucinous cystadenomas are benign cystic tumors which originate from the surface epithelium of the ovary and rarely present during late age. Low grade appendiceal neoplasms (LAMN) are some of the rarest appendiceal tumors and only make up 0.7-1.7% of appendiceal tumor cases. Case Presentation: A 61-year-old woman was referred to the clinic due to a large abdominopelvic mass and complaints of abdominal pain, shortness of breath, and post-menopausal bleeding. She was a multiparous woman (G4P5), 160.02 cm, 121.109 kg and has a BMI of 47.4 kg/m2. She had a history of hypertension, and a previous history of spinal tumor surgery. Imaging studies were significant for a 37 x 27 x 28 cm cystic mass originating from the left adnexa and smaller cysts originating from the right adnexa. Pap smear and endometrial biopsy were negative. Laboratory studies included CA125, CA19-9, and CEA. Those were found to be 11 U/mL (normal < 35 U/mL), 174 U/mL (normal < 34 U/mL), and 0.6 ng/mL (normal < 2.5 ng/mL in an adult nonsmoker) respectively. Given the large size of the masses and elevated CA 19-9, the patient was referred to gynecological oncology for further assessment. After consideration of the imaging, labs, and patient's symptoms, the treatment plan suggested was a total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) to remove the masses. During the TAHBSO, an incidental appendiceal mass was noted and an appendectomy was performed. The gross pathology report revealed that the adnexal masses were bilateral mucinous cystadenomas, and the appendiceal mass was a LAMN. The uterus with the cystic ovaries were found to weigh 11.3 kg and measure 45 x 40 x 30 cm. The large cyst measured 42 cm and the smaller cyst measured 7 cm. The appendix measured 4.5 x 0.7 x 0.7 cm with the LAMN measuring 1.5 cm. The LAMN involved the muscular wall, and the margins were negative. Accordingly, no further treatment was necessary. Conclusion: This case report brings forth a unique case of 61-year-old patient who presented with bilateral mucinous cystadenomas and a LAMN. Mucinous cystadenomas themselves comprise about 15% of ovarian tumors and LAMN make up less than 2% of appendiceal cancers.Item Hypertension at Home: How Telehealth Can Impact Hypertension Screening(2022) Khimani, Faria; Mallory, Brandon; Ojha, Sujata; Wolf, AdamPurpose: Telemedicine is a virtual or hybrid platform of delivering healthcare that has grown tremendously over the last decade thanks to technological advancements. Since the start of the COVID-19 pandemic in 2020, preventive care screenings of hypertension, diabetes, hyperlipidemia, and obesity have significantly declined due to hesitations with in-person visits and staffing limitations in clinics and hospitals. That combined with a significant reduction in physical activity might probe one to think about the adverse impacts the pandemic might have in the cardiac health of the average American. Hypertension, defined here as ≥140mmHg systolic or ≥ 90mmHg diastolic, is a very prevalent pathology in our population and can lead to devastating sequelae such as heart attack, stroke, kidney disease, and dementia. Looking specifically at hypertension management, some limitations to screening include lack of an available blood pressure cuff at home and missed follow-up visits with providers leading to non-renewal of anti-hypertensive medications. This investigation aims to retrospectively study how the pandemic impacted the incidence of hypertension in 2020 and understand what role telemedicine played in providing healthcare screenings to patients. We postulate that there is an increased incidence of hypertension in 2020, during the pandemic, compared to 2019, before the pandemic. Methods: Retrospective data was gathered via chart review of an urgent care telemedicine company on patients aged 18-65. 1,000 charts were de-identified, randomized, and stratified by pre-pandemic (July-December 2019) or pandemic (July-December 2020) periods. The incidence of hypertension was calculated per year. The criteria for hypertension included systolic pressure ≥140mmHg or diastolic blood pressure ≥90mmHg. A two-sample t-test with unequal variance was used to confirm significance. Results: Preliminary analysis, comparing 2019 pre-pandemic visits (n=500) with 2020 pandemic visits (n=232) showed a statistically significant increase in incidence of systolic (20% during the pandemic compared with 16% before the pandemic, p< 0.05) and diastolic (36% during the pandemic compared with 26% before the pandemic, p< 0.05) blood pressure readings. Conclusion: Based on the increased number of hypertensive readings during 2020 compared to 2019, we conclude that there is a higher incidence of hypertension during the COVID-19 pandemic. This finding can be explained by multiple factors and requires further investigation. First, the pandemic severely restricted physical activity with jobs being lost or switched to virtual formats, forcing many to stay home. Second, unhealthy diets and increased caloric intake may have led to increased obesity. Lastly, lack of follow-up with physicians may have led to reduced hypertension screenings allowing more patients to have undiagnosed and untreated hypertension. Telemedicine is one avenue that may address these problems. This platform offers convenience in scheduling and attending appointments, therefore including younger populations that are often abandoned in early screenings. It has a wider reach that is not geographically bound and has the potential to reduce healthcare costs. We hope that this study raises further questions regarding the rise in hypertension during the pandemic and ways to increase early detection of preventable conditions.Item A Novel Method to Characterize Invasive Ductal Carcinoma Tumor Biopsies Using Contact Angle Measurements(2022) Rincon, Julio; Mishra, Ina; Kastellorizios, MichailPurpose: The goal of this work is to develop a preclinical method to characterize human breast cancer biopsies of different racial origin. Contact angle measurements are used to assess the biopsies' surface properties and examine possible correlation with race/ethnicity, tumor type, and cancer grade. This method enables us to study differences in interaction of drugs directly in tumor tissues based on available covariate data of the obtained samples. Here, we present a study of 80 invasive ductal carcinoma tumor samples compared against their matching normal and/or cancer adjacent tissues. Methods: To obtain contact angles of tumor tissues, we developed a contact angle instrument capable of delivering a ~45 nL drop on top of a 1.5 mm biopsy using a modified goniometer with added custom components (DataPhysics Instruments USA Corp.). The system allows us to measure contact angles from 3 different positions (0°, -45°, 90°), and viewing the tumor tissue through an inverted microscope to determine drop position and quality. For this study, breast cancer tissues were obtained as tumor micro arrays (TMA) and as FFPE tissues with matching normal adjacent tissue. For TMA slides, two drops per tissue were delivered and the test was repeated with a subsequent section of the same TMA, unless the TMA included duplicate cores. For FFPE samples, tissues were processed with a microtome at a thickness of 15 µm, a minimum of 6 drops were delivered per tissue. Results: Aggregated data showed normal adjacent tissue (NAT) had an average contact angle (CA) of 51.4° ± 6.5° n=19, cancer adjacent tissue (CAT) had an average CA of 62.8° ± 8° n=59, grade 1 tumors had an average CA of 71.1° ± 7° n=13, grade 2 tumors had an average CA of 67.4 ± 9.1° n=49, and grade 3 tumors had an average CA of 64.6° ± 10.3° n=11. When comparing normal adjacent tissue against any other tissue, p-values ≤ 0.05 and power ≥ 0.80 were observed. When comparing cancer adjacent tissue, only CAT vs NAT and CAT vs grade 2 tumors had p-values ≤ 0.05 and power ≥ 0.80. Individually, 37 cases reached p-values ≤ 0.05 and power ≥ 0.80, were tumor tissue showed contact angles greater than their NAT or CAT. An additional 7 cases met p-values ≤ 0.05 and power ≥ 0.80, however, tumor contact angles were lower than their NAT or CAT. Finally, ignoring type 2 errors, then an additional 11 cases reached p-values ≤ 0.05. Conclusions: Higher contact angles of deionized water were observed in tumor tissues when compared to matching normal or cancer adjacent tissue. It is clear that breast cancer tumors exhibit surface energy differences from normal adjacent tissues, with cancer tissue being more hydrophobic compared to normal tissue. Future work includes the determination of contact angles of Doxil-like liposomes in these tumors and the determination of surface energy of the tissues.Item Practice Effect and Cardiorespiratory Response to Cognitive Test-Retest with Aging(2022) Reddy, Priyanka; Abdali, Kulsum; Ross, Sarah; Davis, Sandra; Shi, XiangrongBackground: This study aimed to examine the age-related difference in practice effect on cognitive performance and cardiorespiratory frequencies during test and retest with the same materials in different cognitive domains. Methods: Twenty cognitively normal older and younger men and women (65±2 vs 26±1 years old) provided the informed consent (approved by IRB) and participated in cognitive test and retest using Mini-Mental State Examination (MMSE), Digit-Span, Trail Making Test (TMT-B), and California Verbal Learning Test (CVLT-II) with ~3 weeks apart. During the testing, heart rate (HR) and breathing frequency (BF) were continuously monitored from electrocardiogram and plethysmograph. ANOVA was applied to examine the significance of the age and retest factors. Results: All cognitive performances were not affected by the age factor or the retest factor except CVLT-II. Baseline cognitive performances of the older vs younger groups were 27.7±1.1 vs 30.5±0.7 (P=0.034) in CVLT-II total Free-Recall, 29.2±0.4 vs 29.6±0.2 in MMSE, 15.6±1.6 vs 16.7±1.2 in Digit-Span, and 58.8±6.4 vs 48.0±3.6 in TMT-B, respectively. The retest factor only significantly improved total Free-Recall in the younger group (P=0.002). Baseline HR and BF were not different between the two groups, older vs younger: 72±5 vs 80±3 beats/min and 17±1 vs 16±1 breaths/min. Both HR and BF were significantly augmented (P< 0.01) in response to the cognitive test. However, both these responses were significantly attenuated during the retest (the retest factor P< 0.01). Only HR, not BF response was significantly affected by the age factor. Conclusions: There was no practice effect on cognitive performances in MMSE, Digit-Span, and TMT-B in both older and younger subjects. Total Free-Recall was significantly improved in the younger subjects only during the retest. There was a practice effect on the cardiorespiratory responses to cognitive challenge, which were significantly reduced during the cognitive retest. Aging significantly diminished HR response during cognitive challenge.Item Unfixed Cadavers as an Adjunct to the Texas College of Osteopathic Medicine POCUS Curriculum(2022) Thomas, Alexander; Son, Min Ji; Jackson, Garrett; Oh, James; Terlizzese, Taylor; Banh, Debini; Burrows, Jack; Quach, Shanon; Vedantam, RahulPURPOSE: Point of care ultrasound (POCUS) continues to grow in its application across all primary care settings due to its wide ranging use and high level of patient safety, especially during medical procedures and aiding in diagnostic accuracy. Advanced technological capabilities in conjunction with affordability gives handheld ultrasound devices the ability to acquire higher quality videos and real time images that are conducive for teaching. Due to these factors, many medical schools are incorporating the use of POCUS into their curricula, including the Texas College of Osteopathic Medicine (TCOM). POCUS is introduced in year 2 as a part of the SIM Lab to help promote development of clinical skills and reasoning. This is implemented via a two-part process in which, alongside systems classes, students complete Sonosim modules that teach about using POCUS on various organ systems. Students then, as part of a skills lab, are aided by student teaching assistants and faculty on proper screening technique utilizing a student volunteer. One key limitation, however, is the fact that the majority of the student volunteers are healthy medical students, which makes it harder to screen for pathology. Due to this limitation, the use of fresh, unfixed cadavers could be a useful adjunct to allow students to further sharpen their POCUS skills while simultaneously seeing pathology in real time. METHODS: A total of 27 unfixed, de-identified cadavers were scanned with a handheld Butterfly iQ+ probe. Sixteen body systems were screened: ocular, thyroid, carotid/internal jugular vein (IJV), brachial plexus, heart, kidneys, pancreas, gallbladder, liver, aorta and the inferior vena cava (IVC), femoral artery and vein, knee, popliteal vessels, uterus, scrotum, and shoulder. RESULTS: Of the 16 body systems, we were able to consistently capture anatomical and pathological images in 8. The body systems that we saw in more than 70% of the screened cadavers include: ocular, thyroid, carotid/IJV, brachial plexus, liver, knee, scrotum, and shoulder. An ultrasound-skilled physician reviewed the images obtained from the cadavers and concluded that for certain body systems the images acquired were indiscernible from anatomy obtained from live patients. Additionally, pathologies discovered in unfixed cadavers were similar to the pathologies seen in live patients. These pathologies include: vitreous detachment, thyroid nodule, liver cyst, hydrocele, and others. CONCLUSION: Ultrasound on unfixed cadavers can be a useful adjunct to the current TCOM ultrasound curriculum. Using cadavers allows room for error and cadavers often have common pathology throughout their system that are rare in healthy student volunteers. Prospective studies should include assessing more body systems and introducing procedures that parallel the current SIM lab curriculum. Additionally, creating artificial pathologies in cadaveric models should be explored to broaden the scope of application.Item Reprogramming of B16-F10 melanoma-educated macrophages by STING agonists loaded in mannose-decorated reconstituted high density lipoprotein nanoparticles.(2022) Dossou, Akpedje; Kapic, Ammar; Mamo, Lois; Sabnis, Nirupama; Lacko, Andras G.; Fudala, RafalPurpose: Representing a large portion of tumor-infiltrating cells, tumor-associated macrophages (TAMs) have the potential to mediate an immune response against the tumor. Instead, they are educated by the tumor microenvironment (TME) to display an immunosuppressive (M2) phenotype that favors tumor progression. The utilization of stimulator of interferon genes (STING) agonists to re-program TAMs to an immunostimulatory (M1) phenotype leads to tumor regression. However, the whole-body distribution of macrophages, the complex TME architecture, and low bioavailability at the TME are challenges to this therapeutic approach. The selective delivery of STING agonists by suitable nanoparticles can help address these challenges. Reconstituted high-density lipoprotein nanoparticles (rHDL NPs) are biocompatible, can penetrate the TME, and interact readily with macrophages. The scavenger receptor class B type 1 (SR-B1) mediates the intracellular delivery of rHDL NPs' payload. Since TAMs highly express scavenger receptors and the mannose receptor CD206, we hypothesize that mannose-decorated rHDL NPs will efficiently deliver STING agonists to TAMs for their repolarization to an M1 phenotype. Thus, the purpose of this study is to assemble and characterize mannose-decorated rHDL NPs and assess the ability of the formulation to deliver STING agonists and polarize B16F10 melanoma-conditioned macrophages to an M1 phenotype. Methods: DSPE-PEG-Mannose (DPM) was used to introduce a mannose moiety onto the rHDL NPs. Two STING agonists (DMXAA, MSA-2) were loaded separately in the rHDL-DPM to form rHDL-DPM-DMXAA and rHDL-DPM-MSA-2. Dynamic light scattering, absorbance- and fluorescence-based measurements were used to evaluate the chemical composition and characterize the formulations. Murine macrophages incubated in B16-F10 melanoma-conditioned media served as an in vitro TAM model. Lipopolysaccharide + interferon-gamma- and interleukin-4 -treated macrophages respectively served as M1 and M2 macrophage references. Western blots and ELISA were used to assess the expression of M1 markers (CXCL10, HLA-DR) and M2 markers (CD36). Results: Similar characteristics, including size, were found for rHDL-DPM-DMXAA and rHDL-DPM-MSA-2. In addition to CD206 expression, B16F10-conditioned macrophages show expression of M2 markers. M2 macrophages and B16-F10-conditioned macrophages showed a higher SR-B1 expression and higher uptake of the payload from rHDL-DPM NPs than M1 macrophages. Treatment with STING agonist-loaded rHDL-DPM diminished CD36 expression and induced HLA-DR and CXCL10 expression in B16F10-conditioned macrophages. Conclusions: The above findings show that the rHDL-DPM NPs can serve as a delivery vehicle for both DMXAA and MSA-2 and potentially can be extended to other TAM-repolarizing drugs. The expression of SR-B1 and payload uptake by the B16-F10-conditioned macrophages validate the utility of rHDL-DPM NPs to efficiently target TAMs. In addition, the induced expression of CXCL10 could be beneficial for the recruitment of CD8+ T-cells when rHDL-DPM NPs are used in combination with T-cell-based immunotherapies to improve treatment outcomes for cancer patients.Item Comparison of dominant and non-dominant knee kinetics in healthy controls versus anterior cruciate ligament reconstruction.(2022) Panchal, Olivia; Goto, Shiho; Singleton, Steven; Dietrich, Lindsay; Hannon, Joseph; Garrison, CraigPurpose/Hypothesis: To examine the knee joint loading with anterior cruciate ligament reconstruction (ACL-R) of the dominant (ACL-D) or non-dominant (ACL-ND) limb at the time of return to sport (RTS) compared to matched healthy controls (CON). Subjects: A total of 150 athletes volunteered. (ACL: N=75, Age=15.56±1.74yrs, Ht=167.93±9.77cm, Mass=67.22±11.39Kg; CON: N=75, Age=15.52±1.91yrs, Ht=168.84±8.33cm, Mass=63.74±11.61Kg). Participants in the ACL-R group underwent ACL-R with a patellar BTB or hamstring graft and were assessed at time of RTS. All subjects in the CON group were considered healthy with no history of lower extremity injury in 3 months prior to testing and IKDC ≥ 95. Materials/Methods: Lower extremity 3-D joint angles and ground reaction force data were collected using an 8 three-dimensional Motion Capture System and force plates. Participants performed 5 double-leg squats (DLS) at a standardized speed (60 bpm). Peak knee extension moment (KnEXTmm) was calculated during the descent phase. Knee joint energy absorption (KnEA) and knee joint energy absorption contribution (KnEAC) were calculated during the same phase. These variables were normalized to the participant's height and weight and averaged across the middle 3 trials. Finally, peak quadriceps (QUADS) isokinetic strength at 60°/sec was assessed, normalized to body weight, and averaged across 3 trials. Separate ANOVAs were performed to examine difference between groups. Comparisons were made between those with ACL-D and the dominant limb of the CON-D and between those with an ACL-ND and the non-dominant limb of CON-ND. Results: In both the ACL-D and ACL-ND groups, KnEA (ACL-D=-0.04±0.02, CON-D=-0.05±0.02; p=0.016. ACL-ND=-0.04±0.01, CON-ND=-0.05±0.01; p< 0.001) and QUADS (ACL-D=1.36±0.51, CON-D=1.79±0.45; p=0.001. ACL-ND=1.40±0.38, CON-ND=1.69±0.41; p=0.001) were significantly decreased compared to controls. KnEAC (ACL-D, CON-D; p>0.05. ACL-ND=51.73±12.54, CON-ND=60.93±9.83; p< 0.001.) and KnEXT mm (ACL-D, CON-D; p>0.05. ACL-ND=-0.04±0.01, CON-ND=-0.05±0.01; p=0.00.) were significantly decreased in the ACL-ND group compared to CON-ND. Significant differences were not observed for these variables between the ACL-D and CON-D groups (p>0.05). Conclusion: Non-significant difference in KnEAC and KnEXTmm in the ACL-D group indicates these subjects performed DLS task at the level observed in the healthy population. However, the significant difference in KnEA in the ACL-D group indicate an overall lower level of loading on the involved limb. All other variables, regardless of side of injury, the ACL-R groups exhibited significantly decreased kinetic and muscle performance relative to healthy controls indicating that side of dominance had little influence on knee biomechanics during DLS at RTS. Clinical Implication: Clinicians should take into consideration which limb underwent ACL-R when designing rehabilitation programs and be aware of these kinetic deficits at the knee joint and attempt to address these differences prior to time of return to sport.Item Sex differences in cerebrovascular dysfunction and hypertension in offspring of hypertensive pregnant rats(2022) Smith, Jonna; Powell, Madison; Cromartie, Whitney; Cunningham, Mark; Duncan, JeremyPURPOSE: Offspring from preeclamptic women have a greater risk of hypertension and cerebrovascular dysfunction later in life. One of the major contributors of cerebrovascular dysfunction is impaired cerebral blood flow (CBF) autoregulation. In the USA, 1 in 25 pregnancies are preeclamptic. Preeclampsia, as defined as new-onset hypertension during pregnancy, is an inflammatory condition characterized by elevated interleukin 17 (IL-17), mitochondrial reactive oxygen species (mtROS), mitochondrial dysfunction (mt-Dys), and intrauterine growth restriction (IUGR). Preliminary work from our laboratory demonstrates that offspring from preeclamptic rats have sex differences. Males have hypertension and a greater impairment of CBF autoregulation, while females have no change in blood pressure with impaired CBF autoregulation. The exact mechanisms for the sex differences in cerebrovascular dysfunction and hypertension is unknown and is the focus of this study. We hypothesize that changes in cerebral mt-dys, cerebral mtROS, and circulating IL-17 contributes to the sex differences in hypertension and cerebrovascular dysfunction in male and female offspring from preeclamptic rats. METHODS: In this study, we compared male and female offspring from normal pregnant and preeclamptic Sprague Dawley rats. All offspring were divided into controls (CON) and IUGR by sex. Hypertensive male and non-hypertensive female offspring's with impaired CBF autoregulation were examined at 17 weeks of age for changes in cerebral mitochondrial electron transport chain (ETC) protein complexes, cerebral manganese superoxide dismutase (MnSOD), and circulating IL-17. RESULTS: Female CON (151±5% IU/Protein/male CON) and IUGR (149±8 %IU/Protein/male CON) offspring have increased MnSOD compared to CON (100±7 %IU/Protein/male CON) and IUGR (122±4 %IU/Protein/male CON) males (p< 0.05). No changes in female ETC protein complexes between IUGR and CON. Male IUGR have a decrease in complex II (71±5 vs. 100±8 %IU/Protein/male CON, p< 0.05) and V (57±2 vs. 100±10 %IU/Protein/male CON, p< 0.05) ETC proteins, and elevated IL-17 (944±370 vs. 412±115 pg/mL, ns) compared to CON males. CONCLUSION: Male IUGR offspring have mt-Dys and elevated IL-17, which may contribute to hypertension and a greater impairment in CBF autoregulation. Female IUGR offspring may be protected due to an increase in mitochondrial antioxidants. In summary, studying the dimorphic sex differences in the mechanisms of hypertension and cerebrovascular dysfunction in offspring of preeclamptic women, may improve the offspring's risk of hypertension, cardiovascular disease, stroke, and cognitive dysfunction later in life.Item Association between sociodemographic and knowledge, attitude, and behavioral factors and Pap test; Health Information National Trends Survey 2020.(2022) Basu, Priyanka; Griner, StaceyPurpose In the past two decades, cervical cancer cases have decreased in the U.S., largely attributed to the secondary prevention by Papanicolaou (Pap) test to detect alterations in cervical cytology. However, racial and ethnic minority women are underscreened and report higher incidence and mortality from cervical cancer. Updated (2018) screening guidelines recommended Pap testing every 3 years for women ages 21-29 years and Pap testing every 3 years, or co-testing with HPV every 5 years, or HPV testing every 5 years for 30-65 years age group. Lack of knowledge regarding risk factors and negative attitudes towards cancer-preventive behaviors may affect adherence to screening recommendations, but research is limited. This study examines the association of sociodemographic and knowledge, attitude, and behavioral factors with adherence to Pap testing among a nationally representative sample of U.S. women. Methods The cross-sectional study was conducted using the 2020 Health Information National Trends Survey (HINTS 5, Cycle 4; n=1,089 women of screening age, 21-65 years). The outcome variable, adherence to cervical cancer screening recommendations were dichotomized into Pap testing within the last 3 years (adherent) or Pap test beyond 3 years/no Pap testing (non-adherent). Questions representing sociodemographic features and knowledge, attitudes, and behavioral measures were selected. Survey-weighted adjusted multivariable logistic regression models were used to assess the association of the sociodemographic and knowledge, attitude, and behavioral factors with Pap testing. Variables associated with Pap test adherence in the regression models were stratified into racial/ethnic groups. Results Approximately 79.3% of women reported being guideline adherent. Most of the sample were Non-Hispanic White women (63.1%), with 61.7% reporting Pap testing guideline adherence. 15.09% of Hispanic women and 14.1% of African American women reported Pap tests within the last 3 years. Compared to women up to high school education, college graduate/post-graduate women (aOR=1.95, 95%CI 1.01-3.79) had higher odds of being guideline adherent. Women with health insurance had higher odds of guideline adherence (aOR=3.60, 95%CI 1.49-8.73), compared to those uninsured. Compared to those with lower knowledge, those with higher knowledge of HPV (aOR=2.41, 95%CI 1.31-4.43) showed higher odds of guideline adherent Pap testing. Non-Hispanic White women with college/post-graduate degree (aOR=3.06, 95%CI 1.27-7.38) and health insurance (aOR=5.26, 95%CI 1.43-19.30) were more likely to be guideline adherent than those with up to high school education and no insurance. The odds of receiving guideline adherent Pap testing are higher for those non-Hispanic White women with knowledge of HPV (aOR=2.98, 95%CI 1.59-5.57) as compared to those who are unaware of it. Conclusion With changes in recommendation guidelines, lack of higher education, lack of health insurance, and lower HPV knowledge may be factors associated with the underscreening of racial and ethnic minority women. Future studies focusing on the HPV and Pap testing knowledge, attitudes, and behaviors of women by race and ethnicity will help to identify and address culture-specific barriers related to Pap testing and ultimately reduce racial disparities in cervical cancer incidence and deaths.Item Disseminated Cryptococcus Neoformans Infection in a Renal Transplant Patient(2022) Tangirala, Praharsha; Mathew, Trina; Lee, Jack; Arispe, Ryan; Yalamanchili, Harika; Sengodan, Mohan; Machaiah, Madhrira; Balamuthusamy, Saravanan; Balamuthusamy, SaravananBackground: Cryptoccocus Neoformans is a fungus mainly found in the environment that infects humans via inhalation and usually affects the lungs and central nervous system. Most people remain asymptomatic; however, immunocompromised patients are most susceptible to this pathogen, particularly HIV/AIDs patients. We present a case of a renal transplant patient with disseminated Cryptococcus Neoformans infection. Case Presentation: A 71 y/o female presents to the emergency department for further evaluation of a fever of unknown origin that has been going on for 6 days. Outpatient workup was initiated by the transplant service; however, due to persistently high fevers she was admitted for further workup and management. Patient reports that her fevers mainly occur at night and reach a maximum of 104-105 F. In the morning the fever decreases to 102 F with Tylenol. Denies any other significant symptoms, recent travel, sick contacts, alcohol, tobacco, or drug use. Past history is significant for CKD due to IgA nephropathy with renal transplant 2.5 years ago. Patient is currently on a chronic immunosuppressive regimen of Mycophenolate and Tacrolimus and infection prophylaxis with TMP-SMX and Valganciclovir. Upon admission, vitals were within normal limits and physical exam was unremarkable. Labs showed negative urinalysis, influenza, COVID-19, and rapid strep antigen test. Lactic acid, magnesium, coagulation studies, TSH, and troponin were all within normal limits. BUN was elevated at 32 and Creatinine at 1.8. White blood cell count was decreased at 2.8k, hemoglobin decreased at 10.9, and hematocrit decreased at 34.2. Chest X-ray showed nodular opacifications involving the right mid to upper lung, possibly masses or mass like infiltrates. Malignancy at this point was high on the differential. CT of the chest was then obtained, which revealed a right upper lobe mass and bilateral pulmonary lymph node involvement that was concerning for metastatic disease. On admission day 2, a CT guided lung biopsy was done. Preliminary reads were suggestive of fungal etiology and no malignancy with the final report of histoplasmosis, but clinical correlation was recommended. On day 5, Cryptococcus Antigen (Ag) titer was obtained and was elevated. On day 6, bronchoscopy with cultures using MALDI-TOF revealed Cryptococcus neoformans and no malignant cells. Given concomitant cytopenia, patient was started on treatment for disseminated Cryptococcal disease with ambisome and flucytosine. However, patient developed an AKI likely from ambisone, and the regimen was switched to PO Voriconazole BID. On day 10, patient was switched to high dose fluconazole. On day 12, repeat Cryptococcal Ag titers showed an increase from 1:40 to 1:320, which was concerning for a high fungal burden. Ambisone was added back on with the fluconazole; however, due to worsening renal function ambisome was held again. Ultimately, the patient wanted to go home and she was discharged on high dose fluconazole per infectious disease recommendation with PCP and transplant service outpatient follow up. Discussion: This case demonstrates that although lobar masses in the elderly can be highly suspicious for malignancy, rarer causes such as Cryptococcus Neoformans should be considered on the differential.Item Presentation and Diagnosis of Phosphoglucomutase Deficiency Type I in a Pediatric Patient(2022) Steele, Cori; Leahy, PeteBackground: Phosphoglucomutase deficiency type 1 (PGM1) is a subtype of congenital disorders of glycosylation (CDG). The type of CDG a patient has is dependent on the gene involved. There are over 130 different types of CDGs, and the defect results in abnormal levels of glucose and galactose metabolites. The diagnosis of CDGs is made by a variety of specialized tests including DNA sequencing, transferrin isoform analysis, or isoelectric focusing. Most CDGs have no direct treatment, but certain disorders have existing therapy and others are in development. It is important to consider CDG in the evaluation of patients who have involvement of multiple organ systems given the potentially treatable nature of these disorders, and the overlap with other disorders. Case Information: We present a patient with phosphoglucomutase (PGM1) deficiency who presented with hypoglycemia and elevated liver function tests. Clinical features of PGM1-CDG involve severe liver and muscle impairment, hypoglycemia, cardiomyopathy, coagulopathies, endocrine and metabolic disorders, neurocognitive delays, and craniofacial abnormalities (cleft palate, bifid uvula, and micrognathia). Abnormal protein glycosylation produces these characteristics, and recurrent hypoglycemia occurs due to insufficient glycogen mobilization. Conclusions: We provide a thorough case history and then discuss the pathophysiology, clinical features, diagnosis, evaluation, and management of PGM1 deficiency. A summary of clinical trial data on the use of galactose supplementation in this rare disorder is provided as is a decision tree in the work-up of hypoglycemia.Item Bilateral Seminal Vesicle Hypoplasia(2022) Cabrero, Daniel; Butson, Carter; Brown, Kerrie; Costello, Kathryn; Fisher, Cara L.Background: Seminal vesicles, two coiled sacs located posteriorly to the male bladder and lateral to the ampulla of the ductus deferens, play a vital role in male fertility. The duct of the seminal vesicle joins with the ampulla of the ductus deferens forming the ejaculatory duct, which then opens into the prostatic urethra. Producing about 70% of male semen, the seminal gland secretes alkaline fluid that contains fructose, prostaglandins, proseminogelin, and other substances that aid in successful fertilization. Contraction of the seminal vesicles releases seminal fluid into the ejaculatory duct where it mixes with spermatozoa from the ductus deferens. Little to no secretions from the seminal vesicles would likely result in male infertility due to the absence of fructose, the primary energy source for motile spermatozoa. Seminal vesicles can be affected by infection, cysts, tumors, hypoplasia, and congenital disease, but isolated seminal vesicle abnormalities are a very uncommon occurrence. There are a few disease states in which seminal vesicle abnormalities do occur. For example, Zinner syndrome is associated with renal agenesis and seminal vesicle hypoplasia or cysts. A Hoxa 13 gene mutation is associated with reduced seminal vesicle size and abnormal morphology, diminished dorsolateral ductal branching of the prostate, and agenesis of the bulbourethral gland. The complete bilateral absence of seminal vesicles can occur following a radical prostatectomy, where the prostate and seminal vesicles are excised together. Case Information: A pelvic dissection of an 82-year-old male donor during a first-year medical anatomy course revealed bilateral seminal vesicle hypoplasia. The seminal vesicle tissue was abnormally tough and embedded within enlarged prostatic tissue. The ductus deferens appeared normal and bilaterally intact. No other significant abnormalities in the reproductive tract nor the kidneys were noted. Conclusions: Based on our current research and ideas, seminal vesicle hypoplasia with no other concurrent reproductive abnormalities is unusual. Apart from the small seminal vesicles, our cadaver had a complete, bilateral set of male internal reproductive organs and an enlarged prostate with no signs of cancer treatment, ruling out the possibility of radical prostatectomy. Due to the presence of an intact urinary tract, Zinner syndrome is unlikely. The most promising possibility for this abnormality is a mutation of the Hoxa 13 gene based on the similarities between this mutation's presentation and our findings.Item GUYON'S CANAL SYNDROME AFTER CUBITAL TUNNEL RELEASE: A CASE REPORT(2022) Yasuda, Tai; Ferguson, Drew; Selod, OmarBackground:Compression of the ulnar nerve typically occurs at the cubital tunnel and less commonly at Guyon's canal. The cubital tunnel is located between the olecranon and the medial epicondyle. A known risk factor for developing cubital tunnel syndrome is repetitive motions at the elbow, commonly found in tennis players and smokers. Guyon's canal is located at the medial wrist between the hook of hamate and pisiform. Compression at Guyon's canal is rare and most commonly occurs in cyclists. In this case, Guyon's canal compression was found after an ulnar nerve decompression and cubital tunnel syndrome in the contralateral extremity. Case Presentation:The patient is a 74-year-old female that presented to the physiatry clinic for bilateral weakness, numbness and tingling in the fourth and fifth fingers. Symptoms in the right hand began approximately eight years ago. She had a right ulnar nerve decompression with persistent numbness since then. Symptoms on the left hand began three months prior to presentation. Social history was significant for an 80-pack year smoking history. Physical exam revealed positive Formant's sign bilaterally and positive Tinel's sign at the right wrist, right elbow, and left wrist. Electrodiagnostic findings were consistent with left sided cubital tunnel syndrome and right sided compression at Guyon's canal. Conclusions:The use of EMG and NCS studies are helpful in diagnosing ulnar nerve lesions. However, if a cubital tunnel syndrome is found, a distal Guyon's canal compression may be masked. In this case, an undiagnosed Guyon's canal compression may have been hidden in the initial EMG study. Additionally, proximal compression of a nerve may contribute to the disruption neurofilament structure, resulting in the distal nerve to be more sensitive to compression.In patients with persistent symptoms of ulnar nerve compression after surgical cubital tunnel release, repeat EMG studies to screen for Guyon's canal compression should be considered.Item Candidate gene analysis of 535 "pain genes" and associations with reported intensity of chronic low back pain(2022) Hurd, Christine A.; Phillips, Nicole R.; Lin, Emily; Broadbent, Dallen; Doederlein, Alexander R.; Dubakula, Vishnu; Licciardone, John C.Purpose: Numerous genome-wide association studies have been able to elucidate potential underlying genetic associations with clinical diagnoses. Chronic low back pain (CLBP) is a clinical presentation that has not yet been strongly associated with specific genetic markers. Several studies however have found genetic associations with other various pain disorders, such as the 535 genes identified by Ultsch et al. as "pain genes." Our group aims to find associations between previously identified pain-related genes and clinical reports of the intensity of low back pain using genetic and clinical data collected by the PRECISION Pain Research Registry. Methods: The PRECISION Pain Research Registry is a national registry that has collected demographic, clinical, and genetic information of patients with CLBP. Our analysis is querying associations between these identified "pain genes" and the intensity of low back pain reported by registry participants using a numerical rating scale (NRS). Methods: Participants in the PRECISION Pain Research Registry were genotyped via an Illumina iScan Array Scanner and Global Screening Array. The phenotype of CLBP will be measured by the NRS, which is an 11-point quantifier of pain intensity. The collected genotypes and phenotypic expression of pain will be compared via the Multi-marker Analysis of GenoMic Annotation (MAGMA), which enables candidate gene analysis of the 535 "pain genes" via congregation of single nucleotide polymorphisms (SNPs) and subsequent projection onto principal components in a matrix. Pain intensity will be evaluated as a function of genetic effects accounting for selected covariates-comorbid conditions with a documented relationship to CLBP, smoking status, and genetic ancestry plus residuals, with F-tests to determine the p-values of associations. Results: FN1 and STARD13 were found to be significantly associated with pain intensity in AA registry participants and VEGF-A was found to be significantly associated with widespread pain in NHW registry participants Conclusion: For treatment that is refractory to other strategies, targeted drugs for these protein products can be explored as treatments. These mentioned genes also have significant epigenetic regulation that could be explored in further studies.Item Effects of Osteogenesis Imperfecta on Dental Tissue Volumes in Mice(2022) Moore, Jacob; Handler, Emma; Menegaz, Rachel A.; Gonzales, Lauren; Organ, JasonOsteogenesis imperfecta (OI), commonly known as brittle bone disease, is associated with lifelong dental problems, including increased dental fractures, discolored teeth, and malocclusion. OI is a disorder of the type I collagen protein. Insufficient amounts or misshapen forms of this protein lead to disruptions in the microstructure of bone and teeth tissues. Dentin, the hard tissue which comprises the bulk of the tooth and absorbs shock forces during chewing, develops on a type I collagen matrix. Thus, collagen abnormalities in OI lead to disorganized and less stable dentin. Further, teeth in people with OI frequently exhibit dentin hypertrophy, where increased amounts of dentin are deposited at the interior of the tooth, shortly after dental eruption. Enamel, unlike dentin, develops on a matrix of non-collagenous proteins, and is thought to develop normally in OI. However, abnormalities in the underlying dentin in OI can lead to enamel fractures. Finally, the teeth in people with OI have often been noted to be smaller than those of people without OI. Because dental development occurs early in life, there is a lack of data surrounding the developmental processes and associated issues in dental development of children with OI. Mice are commonly used models for dental development, yet, this process has not yet been studied in mice. The objective of this study is to compare dental tissue volumes of teeth from mice with OI (oim) and wild type mice (wt) at different developmental stages to determine the degree of volume and gross dental size differences during late growth stages. Three-dimensional models of upper and lower first molars and incisors were created from microCT scans from oim and wt mice. Scans were taken at weaning age (four weeks after birth; "W4") and young adulthood (sixteen weeks after birth; "W16"). Dental tissue volumes were measured using 3D Slicer and normalized to mandibular centroid size. Mann-Whitney U tests were used to compare tissue volumes between genotypes and age groups. At W4 and W16, oim mice had significantly lower dentin volumes and total tooth volumes for upper incisors than wt mice (p < 0.05), with no significant difference between groups for other tooth types at either timepoint. At W16, total tooth volume was significantly lower in oim mice for molars before adjusting for mandible size (p < 0.05). For both oim and wt groups, W16 mice had significantly greater dentin, enamel, and total tissue volumes for lower and upper incisors compared to W4 mice (p < 0.05), as well as greater dentin volumes for lower molars (p < 0.05). These results demonstrate that the trend of smaller teeth in humans with OI also holds for the oim mouse. These differences are present at both the juvenile and young adult life stages. This affirms the oim mouse as a possible model for dental development in humans with OI. Further studies are needed to determine the developmental program of these volume differences at earlier growth stages.Item A Drug-Loaded Nanoparticle to Target Bone-Metastatic Prostate Cancer(2022) Lampe, Jana B.; Desai, Priyanka; Tripathi, Amit K.; Ranjan, Amalendu; Vishwanatha, JamboorTreatment for localized prostate cancer (PCa) has a tremendous success rate. However, the fact that the five-year overall survival rate drops from 100% to 30.2% when tumor cells metastasize to distant sites, represents an unmet medical need. In 90% of metastatic cases, bone is the primary metastatic site. Our objective is to co-load a poly(lactic-co-glycolic) (PLGA) nanoparticle (NP) with Cabazitaxel (CBZ) and Bortezomib (BTZ) and to conjugate a bone-targeting moiety, Alendronate (ALN), to the outside of the nanoparticle to facilitate targeting to bone tumors and to ameliorate the resulting bone damage. We hypothesize that this targeted nanomedicine will affect genes and proteins that contribute to invasion and migration, anti-apoptotic signaling, and ultimately lead to tumor-cell apoptosis. Furthermore, we predict that the nano-delivery system will help ameliorate bone lesions inflicted by the tumors. Methods: Nanoparticles were engineered using an Emulsion-Diffusion-Evaporation Technique in which PLGA is dissolved in dichloromethane, 5% polyvinyl alcohol, and Bis(sulfosuccinimydyl)suberate (BS3) crosslinker. For targeting, Alendronate (ALN) is later conjugated to the outside of the nanoparticle via this crosslinker. Results: Our average NP size was around 240 nm in diameter, a PDI of < 0.2, with a Zeta Potential (ZP) of -28 mV. Our drug loading capacity (DL) for CBZ was 11.97% and for BTZ 0.9%. Encapsulation efficiency (EE) for CBZ was 25.26% and 8.9% for BTZ. The IC50 for the CBZ NPs is 5.6 nM and BTZ NPs is 15.6 nM. We have successfully shown that the gene expression for various migration and invasion markers as well as cell signaling proteins have been affected by the nanoparticles. Conclusions: Our nanoparticles have a desirable size, PDI, ZP, DL, and EE for our intended therapeutic purpose. Furthermore, we have shown alterations in the cell signaling and gene expression responsible for Epithelial-to-Mesenchymal Transition-Transcription Factors (EMT-TFs), indicating that our nanotherapeutic has significant potential to treat metastatic PCa and to mitigate the damage done by metastatic tumors.Item Characterization of Estrogen Receptors (ERs) and ER-metabolizing enzymes in Lipedema and Non-Lipedema Adipose Stem Cells (ASCs) and differentiated adipocytes(2022) Walczak, Samantha; Al-Ghadban, Sara; Rinderle, Caroline; Bunnell, BruceIntroduction: Lipedema is a chronic, idiopathic painful disease characterized by an excess of adipose tissue in the lower extremities, commonly misdiagnosed as obesity, lymphedema, or chronic venous insufficiency. As the severity of lipedema worsens patients have reduced mobility, easy bruising, and fatigue and it is thought to resist lifestyle modifications. While treatments such as liposuction can help ease these symptoms, it is not curative, and the underlying etiology is unknown. Hypothesis: As the development of lipedema often begins or worsens during periods of hormonal change such as puberty, pregnancy, or menopause, we hypothesize that alterations in estrogen drive lipedema pathogenesis. Aim: The aim of this study is to characterize the gene expression of estrogen receptors (ER-α and ER-β), G-protein coupled estrogen receptor (GPER), and ER metabolizing enzymes: Hydroxysteroid 17-beta dehydrogenase (HSD17B1, B7, B12), Hormone-sensitive Lipase (LIPE) and Steroid Sulfatase (STS) in ASCs and differentiated adipocytes in BMI and age-matched non-lipedema and lipedema patients. Methods: Cell culture and Oil Red O stain, RNA extraction and RT-PCR assays were used to assess the expression of ERs and the estrogen metabolizing enzymes in ASCs and differentiated adipocytes. Results: ER-α, ER-β, and GPER gene expression were increased in Lipedema ASCs cultured in hormone-depleted media, as well as in differentiated adipocytes compared to non-lipedema corresponding cells. LIPE, STS, HSD17B17, and HSD17B12 gene expression were also increased in Lipedema differentiated adipocytes compared to non-lipedema differentiated adipocytes. In addition, the gene expression of HSD17B1 was increased in Lipedema ASCs cultured in hormone-depleted media compared to non-lipedema ASCs. Conclusion: These results indicate that expression of ERs and estrogen metabolizing enzymes are altered by Lipedema and suggest that estrogen may play a role in adipose tissue dysregulation in lipedema. Exploring this possible etiology further could contribute to the expansion of treatment options and management available to lipedema patients.Item Incidental finding of gallbladder adenocarcinoma in the 2nd trimester of an otherwise healthy pregnant woman.(2022) Cushen, Spencer; Logarajah, Shankar; Kabbani, Wareef; Osman, Houssam; Jeyarajah, RohanBackground Pregnancy causes an increased production of steroid sex-hormones resulting in more cholesterol laden bile and decreased gallbladder emptying. This results in greater incidence of gallbladder disease in pregnant women with 10% of pregnant women developing gallstones or sludge and a further 1% of these developing symptomatic disease. In addition to simple gallstone disease, multiple pregnancies increase the risk of gallbladder in cancer. In this Case Report, we present what is, to our knowledge, the first report of incidental gallbladder adenocarcinoma in an otherwise healthy pregnant woman. Case Presentation A 36-year-old woman presented to the emergency department with right upper quadrant abdominal pain at 16 weeks of gestation. A clinical picture of acute cholecystitis was developed and confirmed by ultrasound demonstrating sonographic Murphy's sign, gallbladder containing gallstones, 2 mm thick gallbladder wall, and pericholecystic fluid. This patient then underwent laparoscopic cholecystectomy. Routine pathologic assessment of the gallbladder demonstrated a 3.9 cm calculus, 2.5 cm wide high-grade dysplasia, and a 1.0 cm invasive, moderately differentiated adenocarcinoma. This malignant lesion extended through the wall of the gallbladder, giving it a tumor classification of pT2a. The patient was then referred to the hepatopancreaticobiliary (HPB) surgery service for completion of an extended cholecystectomy as indicated to stage the cancer and remove additional disease. After this surgery no lymph nodes, cystic duct margins, or liver sections collected for pathology demonstrated malignancy, giving the final TNM classification of pT2aN0M0R0, Stage IIA. On 6 month follow up patient had received chemotherapy and was free of evidence of malignancy on MRI. Conclusions To our knowledge this is only the second case report demonstrating a pregnant woman being diagnosed with gallbladder cancer. In the other report, the woman had Crohn's disease and gallbladder changes consistent with Crohn's disease. Therefore, this is the first presentation of an otherwise healthy pregnant woman being incidentally diagnosed with gallbladder cancer after acute gallstone disease. This report adds to the current understanding of pregnancy induced gallstone disease by providing a rare end point to such disease processes.Item The impact of healthy pregnancy on maternal cognitive impairment in Sprague Dawley rats(2022) Wilson, E. Nicole; Bradshaw, Jessica L.; Tucker, Selina; Gardner, Jennifer; Goulopoulou, Styliani; Cunningham, RebeccaIntroduction/Background: There is clinical evidence of impaired attention, learning, and memory in pregnant women during pregnancy and in the postpartum period, suggesting an association between pregnancy and maternal cognitive dysfunction. Yet, the effects of pregnancy on memory impairment are unclear. We hypothesized that pregnancy would induce maternal cognitive dysfunction that would persist postpartum in a rat model of healthy pregnancy. Methods: To observe recollective memory, the novel object recognition test was performed using Sprague Dawley female rats with different reproductive histories [non-pregnant virgin, late gestation (gestational day 20, term = 22-23 days), postpartum (28 days after birth), and parous non-pregnant (60 days after birth); n = 7-8/group]. Each rat was placed into an empty arena without objects, to allow for adjustments to the open arena. Thirty-minutes after habituation, each rat was given a period of five minutes to explore the arena with two objects of identical size, color, and texture. Upon completion, one hour was given before the animal was placed back in the arena. To test short term recollective memory, each rat was given three minutes to explore two items: one familiar item and a novel item of different size, color, and texture. The latency to which the animal made the initial contact for each object was recorded, and the number of contacts made with the novel object were tallied and compared with overall contacts to each object. Results: Pregnant rats had increased latency to initial contact of the novel object (p < 0.05) compared to virgin females, postpartum dams, and parous non-pregnant dams. Additionally, parous, non-pregnant dams displayed significantly greater contacts with the novel object (p < 0.05) compared to pregnant rats and postpartum dams. Conclusion: Overall, healthy pregnancy results in decreased short term memory recognition that can be repaired over time. Future directions include evaluating the impact of healthy pregnancy on long term memory recognition, examining underlying mechanisms contributing to cerebral impairments during pregnancy, and determining the effects of pregnancy complications on memory impairment.