Digital Commons Network^™

Understanding The Role Of Ampa Receptors In Autism: Insights From Circuit And Synapse Dysfunction, Andres Jimenez-Gomez, Megan X Nguyen, Jason S Gill

Faculty, Staff and Students Publications

Autism spectrum disorders represent a diverse etiological spectrum that converge on a syndrome characterized by discrepant deficits in developmental domains often highlighted by concerns in socialization, sensory integration, and autonomic functioning. Importantly, the incidence and prevalence of autism spectrum disorders have seen sharp increases since the syndrome was first described in the 1940s. The wide etiological spectrum and rising number of individuals being diagnosed with the condition lend urgency to capturing a more nuanced understanding of the pathogenic mechanisms underlying the autism spectrum disorders. The current review seeks to understand how the disruption of AMPA receptor (AMPAr)-mediated neurotransmission in the …

Compton Scattering Of Mammographic Soft X-Ray Beams By Alkali And Transition Metal Salt Filters Produce X-Ray Interference Zones That May Have Treatment Potential For Localized Cancer Lesions, Subhendra N. Sarkar, Eric Lobel, Sabina Rakhmatova, Derbie Desir, Somdat Kissoon, Daler Djuraev, Katie Tam

Publications and Research

In breast x-ray imaging scattered radiation adds 50% of harmful radiation dose from anisotropic Compton scattering mechanism. We have been working with double layered inorganic salt materials that can induce Compton scattering to the incident mammographic x ray beams (in 20-30 kVp range) with adequate isotropy (angular control). Typically metal nitrates and alkali halide salt layers are shown here to cause low energy radiation interference zones with high and low photon intensities and local flux heterogeneity in terms of flux covariance. Spatial variation of low energy photon flux creates concentrated and sparse radiation zones that may be used to induce …

Circular Economy: The 4rs Reduce-Reuse-Recycle-Recover, Kevin Hom

Publications and Research

This article summarizes the lecture presented at the Net Built 2024 conference. The lecture addresses the unsustainability of the current linear economy, characterized by the "take, make, dispose" model, in light of environmental challenges. The inefficiencies of this system lead to increased energy consumption, elevated CO2 emissions, and the exacerbation of climate change. It examines the current state of design and construction with respect to climate change and sustainable resource management. Additionally, the lecture introduces a methodology that integrates technologies and design philosophies capable of driving significant positive change. By advocating for a transformative approach to the expected lifetime of …

New York State Climate Impacts Assessment: 04 Buildings, Nicholas B. Rajkovich, Carrie Brown, Ilya Azaroff, Erik Backus, Shannon Clarke, Jared Enriquez, Bethany Greenaway, Meghan T. Holtan, Jamal Lewis, Ozgem Ornektekin, Laurie Schoeman

Publications and Research

New York State has nearly 5.3 million buildings, and all of them are vulnerable in some way to the impacts of climate change. Understanding these impacts is critical, because risks to buildings not only threaten individual lives but also pose threats to community-level resilience. This chapter examines the impacts of climate change on buildings and, by extension, the people and communities they shelter and support. It also highlights building types and populations that are at particular risk and presents adaptation strategies to protect the state’s existing and future building stock from climate impacts.

‘I Know It When I See It’– Developing Quality Schedules Considering Subjective Or Unspecified Criteria, Douglas L. Moody

Publications and Research

Most timetabling problems have a given objective function to measure the quality of a solution. However, users may have a “I know it when I see it” recognition of a quality schedule, without specifying the complete basis for their judgment. In this situation, the objective function cannot be exclusively used as a solution quality measurement. This work presents an AI based approach to aid in categorizing the solution’s quality when the users have not explicitly defined all factors used in their criteria.

Call The Experts: Identifying Stakeholders In The Long-Term Care Of Youth With Hypospadias, Vinaya P Bhatia, Kristin Ebert, Shannon Cannon, Walid A Farhat, Heidi W Brown, Jane Mahoney, Marisa E Hilliard, Kristina L Penniston

Faculty, Staff and Students Publications

Long-term follow-up for individuals with hypospadias remains a critical area of need, yet evidence-based guidelines for such follow-up are lacking, and the role of involvement of relevant experts is not yet established. Using our hypospadias-specific health-related quality of life conceptual framework and a subsequent qualitative study of prepubertal males and parents of males with hypospadias, we identified potential priorities for long-term follow-up of youth with hypospadias. Using thematic codes from our patient and parent interviews, we searched PubMed for relevant articles and identified the specialties represented by all the authors of these articles. Our search strategy revealed consistent expertise across …

Predictors Of Making A Referral To Child Protective Services Prior To Expert Consultation, Danielle Zamalin, Irene Hamlin, Justine Shults, M Katherine Henry, Kristine A Campbell, James D Anderst, Angela N Bachim, Rachel P Berger, Lori D Frasier, Nancy S Harper, Megan M Letson, John D Melville, Daniel M Lindberg, Joanne N Wood

Faculty, Staff and Students Publications

OBJECTIVE: Suspicion for child abuse is influenced by implicit biases. Evaluation by a Child Abuse Pediatrician (CAP) may reduce avoidable child protective services (CPS) referrals. Our objective was to investigate the association of patient demographic, social and clinical characteristics with CPS referral before consultation by a CAP (preconsultation referral).

METHODS: Children <5 years-old undergoing in-person CAP consultation for suspected physical abuse from February 2021 through April 2022 were identified in CAPNET, a multicenter child abuse research network. Marginal standardization implemented with logistic regression analysis examined hospital-level variation and identified demographic, social, and clinical factors associated with pre-consultation referral adjusting for CAP’s final assessment of abuse likelihood.

RESULTS: Among the 61% (1005/1657) of cases with preconsultation referral, the CAP consultant had low concern for abuse in 38% (384/1005). Preconsultation referrals ranged from 25% to 78% of cases across 10 hospitals (P < .001). In multivariable analyses, preconsultation referral was associated with public insurance, caregiver history of CPS involvement, history of intimate partner violence, higher CAP level of concern for abuse, hospital transfer, and near-fatality (all P < .05). The difference in preconsultation referral prevalence for children with public versus private insurance was significant for children with low CAP concern for abuse (52% vs 38%) but not those with higher concern for abuse (73% vs 73%), (P = .023 for interaction of insurance and abuse likelihood category). There were no differences in preconsultation referral based on race or ethnicity.

CONCLUSIONS: Biases based on socioeconomic status and social factors may impact decisions to refer to …

5-Htp Inhibits Eosinophilia Via Intracellular Endothelial 5-Htrs; Snps In 5-Htrs Associate With Asthmatic Lung Function, Matthew T Walker, Jeffrey C Bloodworth, Timothy S Kountz, Samantha L Mccarty, Jeremy E Green, Ryan P Ferrie, Jackson A Campbell, Samantha H Averill, Kenneth B Beckman, Leslie C Grammer, Celeste Eng, Pedro C Avila, Harold J Farber, William Rodriguez-Cintron, Jose R Rodriguez-Santana, Denise Serebrisky, Shannon M Thyne, Max A Seibold, Esteban G Burchard, Rajesh Kumar, Joan M Cook-Mills

Faculty, Staff and Students Publications

BACKGROUND: Previous research showed that 5-hydroxytryptophan (5HTP), a metabolic precursor of serotonin, reduces allergic lung inflammation by inhibiting eosinophil migration across endothelial monolayers.

OBJECTIVE: It is unknown if serotonin receptors are involved in mediating this 5HTP function or if serotonin receptor (HTR) single nucleotide polymorphisms (SNPs) associate with lung function in humans.

METHODS: Serotonin receptor subtypes were assessed by qPCR, western blot, confocal microscopy, pharmacological inhibitors and siRNA knockdown. HTR SNPs were assessed in two cohorts.

RESULTS: Pharmacological inhibition or siRNA knockdown of the serotonin receptors HTR1A or HTR1B in endothelial cells abrogated the inhibitory effects of 5HTP on eosinophil …

Ginkgo Biloba For Tardive Dyskinesia And Plasma Mnsod Activity: Association With Mnsod Ala-9val Variant: A Randomized, Double-Blind Trial, Dongmei Wang, Yang Tian, Jiajing Chen, Rongrong Zhu, Jiaxin Li, Huixia Zhou, Dachun Chen, Li Wang, Thomas R Kosten, Xiang-Yang Zhang

Faculty, Staff and Students Publications

Background: Excessive free radicals are implicated in the pathophysiology of tardive dyskinesia (TD), and Ginkgo biloba extract (EGb761) scavenges free radicals, thereby enhancing antioxidant enzymes such as mitochondrial manganese superoxide dismutase (MnSOD). This study examined whether EGb761 treatment would improve TD symptoms and increase MnSOD activity, particularly in TD patients with specific MnSOD Val-9Ala genotype.

Methods: An EGb761 (240 mg/day) 12-week double-blind clinical trial with 157 TD patients was randomized. The severity of TD was measured by the Abnormal Involuntary Movement Scale (AIMS) and plasma MnSOD activity was assayed before and after 12 weeks of treatment. Further, in an expanded …

Outcomes For Patients With Head And Neck Sarcoma Treated Curatively With Radiation Therapy And Surgery, Alison K Yoder, Ahsan Farooqi, Devarati Mitra, J Andrew Livingston, Dejka M Araujo, Erich M Sturgis, Ryan Goepfert, Andrew J Bishop, B Ashleigh Guadagnolo

Faculty, Staff and Students Publications

Purpose: Soft tissue sarcomas (STSs) of the head and neck (H&N) are rare malignancies that are challenging to manage. We sought to describe the outcomes of patients treated with curative intent using combined surgery and radiation therapy (RT) for H&N STS.

Methods and materials: We performed a single-institution retrospective review of patients with nonmetastatic STS of the H&N who were treated from 1968 to 2020. The Kaplan-Meier method was used to estimate disease-specific survival (DSS) and local control (LC). Multivariable analyses (MVAs) were conducted using Cox proportional hazards model.

Results: One hundred ninety-two patients had a median follow-up of 82 …

Molecular Profiling Of A Hepatocellular Neoplasm Not Otherwise Specified (Hcn-Nos) Demonstrates Distinct Molecular Features In Hepatoblastoma And Hcc-Like Components, Yan Chen Wongworawat, Stephen F Sarabia, Martin Urbicain, Paola Francalanci, Pavel Sumazin, Rita Alaggio, Dolores H López-Terrada

Faculty, Staff and Students Publications

Hepatoblastomas (HB) are embryonal tumors with quiet genomes diagnosed mostly in children under 3 years of age and often cured by surgical resection and chemotherapy. However, a subset of HBs behave aggressively, displaying characteristic histologic features and higher genomic instability. Hepatocellular neoplasm-not otherwise specified (HCN-NOS) is a provisional diagnostic category for tumors exhibiting either intermediate or a combination of both HB and hepatocellular carcinoma (HCC) histological features. In this study, we characterized an HCN-NOS diagnosed in a 3-year-old patient presenting with a liver mass, in which both HB and HCC histological components were amendable to macro-dissection and molecular profiling. The …

The Mars Complex: A Critical Mediator Of Immune Regulation And Homeostasis, Sharon Bright Amanya, Damilola Oyewole-Said, Keenan J Ernste, Nalini Bisht, Arnav Murthy, Jonathan Vazquez-Perez, Vanaja Konduri, William K Decker

Faculty, Staff and Students Publications

Over the course of evolution, many proteins have undergone adaptive structural changes to meet the increasing homeostatic regulatory demands of multicellularity. Aminoacyl tRNA synthetases (aaRS), enzymes that catalyze the attachment of each amino acid to its cognate tRNA, are such proteins that have acquired new domains and motifs that enable non-canonical functions. Through these new domains and motifs, aaRS can assemble into large, multi-subunit complexes that enhance the efficiency of many biological functions. Moreover, because the complexity of multi-aminoacyl tRNA synthetase (mARS) complexes increases with the corresponding complexity of higher eukaryotes, a contribution to regulation of homeostatic functions in multicellular …

High-Fat Diets Promote Peritoneal Inflammation And Augment Endometriosis-Associated Abdominal Hyperalgesia, Tristin Herup-Wheeler, Mingxin Shi, Madeleine E Harvey, Chandni Talwar, Ramakrishna Kommagani, James A Maclean, Kanako Hayashi

Faculty, Staff and Students Publications

Immune dysfunction is one of the central components in the development and progression of endometriosis by establishing a chronic inflammatory environment. Western-style high-fat diets (HFD) have been linked to greater systemic inflammation to cause metabolic and chronic inflammatory diseases, and are also considered an environmental risk factor for gynecologic diseases. Here, we aimed to examine how HFD cause an inflammatory environment in endometriosis and discern their contribution to endometriotic-associated hyperalgesia. Our results showed that HFD-induced obesity enhanced abdominal hyperalgesia that was induced by endometriotic lesions. Peritoneal inflammatory macrophages and cytokine levels increased by lesion induction were elevated by chronic exposure …

Pharmacological Inhibition Of The Map2k7 Kinase In Human Disease, H Daniel Lacorazza

Faculty, Staff and Students Publications

The MAP2K7 signaling pathway activates the c-Jun NH2-terminal protein kinase (JNK) in response to stress signals, such as inflammatory cytokines, osmotic stress, or genomic damage. While there has been interest in inhibiting JNK due to its involvement in inflammatory processes and cancer, there is increasing focus on developing MAP2K7 inhibitors to enhance specificity when MAP2K7 activation is associated with disease progression. Despite some progress, further research is needed to fully comprehend the role of MAP2K7 in cancer and assess the potential use of kinase inhibitors in cancer therapy. This review examines the role of MAP2K7 in cancer and the development …

Rapid Gene Fusion Testing Using The Nanostring Ncounter Platform To Improve Pediatric Leukemia Diagnoses In Sub-Saharan Africa, Julie M Gastier-Foster, Fredrick Lutwama, Olive Mbabazi, Steven Mlenga, Kennedy Ulaya, Ruth Namazzi, E Faith Hollingsworth, Dolores Lopez-Terrada, Kevin E Fisher, Angshumoy Roy, Carl E Allen, David G Poplack, Rizine Mzikamanda, Nmazuo Ozuah, Peter Wasswa

Faculty, Staff and Students Publications

Risk stratification and molecular targeting have been key to increasing cure rates for pediatric cancers in high-income countries. In contrast, precise diagnosis in low-resource settings is hindered by insufficient pathology infrastructure. The Global HOPE program aims to improve outcomes for pediatric cancer in Sub-Saharan Africa (SSA) by building local clinical care and diagnostic capacity. This study aimed to assess the feasibility of implementing molecular assays to improve leukemia diagnoses in SSA. Custom NanoString nCounter gene fusion assays, previously validated in the US, were used to test samples from suspected leukemia patients. The NanoString platform was chosen due to relatively low …

Lack Of Association Of A1c With Postoperative Complications In Children With Type 1 Or Type 2 Diabetes, Grace Kim, Mckenna C Richards, Abigail B Smith, Kathleen M Strybos, Xiaofan Huang, Kristen Staggers, Stephen A Stayer, Rahul G Baijal

Faculty, Staff and Students Publications

Not meeting recommended A1C targets may be associated with postoperative complications in adults, but there are no studies reporting on the relationship between preoperative A1C and postoperative complications in children with type 1 or type 2 diabetes. The objective of this study was to determine whether elevated A1C levels were associated with an increased incidence of postoperative complications in children with diabetes presenting for elective noncardiac surgery or diagnostic procedures. It found no such association, suggesting no need to delay elective surgery in children with diabetes until A1C is optimized.

Diagnostic Accuracy Of Urinary N Terminal Pro-B Type Natriuretic Peptides For Hemodynamically Significant-Patent Ductus Arteriosus In Preterm Infants, Srirupa Hari Gopal, Ganga Gokulakrishnan, Madhulika Kulkarni, Caraciolo J Fernandes, Mohan Pammi

Faculty, Staff and Students Publications

Background: Echocardiography is the gold standard for the diagnosis hemodynamically significant-patent ductus arteriosus (hs-PDA). It requires trained personnel and is not readily available. Urinary biomarkers can be used as an adjunct.

Objective: The objective of this study was to systematically review the diagnostic accuracy of urinary N terminal pro-B type natriuretic peptides (NT-proBNP) for hs-PDA in preterm neonates.

Methods: We included studies that evaluated urinary NT-proBNP and urinary NT-proBNP/creatinine ratio (index tests) in preterm neonates with hs-PDA (participants) in comparison with echocardiogram (reference standard). Methodological quality and certainty of evidence were assessed using Quality Assessment of Diagnostic-Accuracy Studies (QUADAS-2) and …

Physical Violence And Aggression In Parkinson's Disease: A Systematic Review, Melissa B Jones, Lakeshia Gibson, Malena Gimenez-Zapiola, Ana Guerra, Gursimrat Bhatti, Dakota Broadway, Juliann Tea, Aksa Prasad, Rachel Gates, Elizabeth Hinton, Ricardo E Jorge, Laura Marsh

Faculty, Staff and Students Publications

Background: Physical violence and aggression (PVA), defined as behaviors with the potential to cause bodily injury, are unfortunate risks in the management of all-cause neurodegenerative dementias. While dementia in Parkinson's disease (PD) may not be evident for many years after clinical onset, neuropsychiatric disturbances occur at all stages of the disease. At issue is whether PVA in PD is associated with clinical factors that can be targets for prevention and management in the absence of a prevailing dementia syndrome.

Objective: This systematic review examined the extent to which PVA in PD without dementia is a clinically significant concern and whether …

Emulating A Randomized Clinical Trial With Real-World Data To Evaluate The Effect Of Antidepressant Use In Ptsd Patients With High Suicide Risk, Oshin Miranda, Xiguang Qi, M Daniel Brannock, Ryan Whitworth, Thomas Kosten, Neal David Ryan, Gretchen L Haas, Levent Kirisci, Lirong Wang

Faculty, Staff and Students Publications

INTRODUCTION: Post-Traumatic Stress Disorder (PTSD) entails behavioral changes with increased risk of suicide, and there is no consensus on the preferred antidepressants for treatment of those PTSD patients who are at elevated risk for suicide.

METHODS: We conducted a clinical trial emulation study comparing suicide-related events (SREs) among those patients' initiating antidepressants within 60 days after a qualifying SRE. Patients were followed from initiation of antidepressant until any of the following: treatment cessation, switching, death, or loss to follow-up. The outcome is a new onset of an SRE.

RESULTS: Citalopram exhibited a significantly fewer case with new SREs compared to …

Racial Disparities In Thoracic Aortic Surgery: Myth Or Reality?, Ourania Preventza, Elizabeth Akpan-Smart, Khan Lubna, Katherine Simpson, Lorraine Cornwell, Sydney Schmitt, Hiruni S Amarasekara, Scott A Lemaire, Joseph S Coselli

Faculty, Staff and Students Publications

Objective: We examined the relationship between Black or White race and adverse outcomes in patients who underwent surgery of the ascending aorta, aortic root, or aortic arch at our center.

Methods: We analyzed 2335 consecutive patients who identified as Black (n = 217, 9.3%) or White (n = 2118, 90.7%) and underwent proximal aortic surgery. Patient zip codes were used to determine community socioeconomic (CSE) characteristics. The composite adverse outcome comprised mortality, persistent neurologic injury, and renal failure necessitating dialysis at discharge. We performed multivariable analysis, Kaplan-Meier analysis, and propensity score matching adjusted for CSE factors.

Results: Median follow-up time …

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis In An Orthotopic Liver Transplant Recipient: A Case Report, Chun-Sing Huang, Emily Strouphauer, Christine O'Mahony, Nhu T N Galván, Ronald Cotton, John Goss, Abbas Rana

Faculty, Staff and Students Publications

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare spectrum of acute, mucocutaneous drug reactions characterized by epidermal necrosis of the skin and mucous membranes with progressive multiorgan failure. Cutaneous presentation of SJS/TEN is similar to that of acute graft-versus-host disease, creating a diagnostic dilemma in solid-organ transplant recipients presenting with diffuse, erythematous eruptions, skin sloughing, and systemic sequelae, reflective of both diseases. This case report details a 48-year-old woman post-orthotopic liver transplantation (OLT) who developed a diffuse, painful, morbilliform rash with progressive desquamation, along with corresponding pathological analysis indicative of SJS/TEN. There are few documented reports of SJS/TEN in solid-organ …

Self-Rectifying Magnetoelectric Metamaterials For Remote Neural Stimulation And Motor Function Restoration, Joshua C Chen, Gauri Bhave, Fatima Alrashdan, Abdeali Dhuliyawalla, Katie J Hogan, Antonios G Mikos, Jacob T Robinson

Faculty, Staff and Students Publications

Magnetoelectric materials convert magnetic fields into electric fields. These materials are often used in wireless electronic and biomedical applications. For example, magnetoelectrics could enable the remote stimulation of neural tissue, but the optimal resonance frequencies are typically too high to stimulate neural activity. Here we describe a self-rectifying magnetoelectric metamaterial for a precisely timed neural stimulation. This metamaterial relies on nonlinear charge transport across semiconductor layers that allow the material to generate a steady bias voltage in the presence of an alternating magnetic field. We generate arbitrary pulse sequences with time-averaged voltage biases in excess of 2 V. As a …

Monoclonal Antibodies In Neuro-Ophthalmology, Caroline C Keehn, Arman Yazdian, Patrick J Hunt, Pamela Davila-Siliezar, Noor A Laylani, Andrew G Lee

Faculty, Staff and Students Publications

Neuro-ophthalmologic diseases include a broad range of disorders affecting the afferent and efferent visual pathways. Recently, monoclonal antibody (mAb) therapies have emerged as a promising targeted approach in the management of several of these complex conditions. Here, we describe the mechanism-specific applications and advancements in neuro-ophthalmologic mAb therapies. The application of mAbs in neuro-ophthalmologic diseases highlights our increasing understanding of disease-specific mechanisms in autoimmune conditions such as neuromyelitis optica, thyroid eye disease, and myasthenia gravis. Due to the specificity of mAb therapies, applications in neuro-ophthalmologic diseases have yielded exceptional clinical outcomes, including both reduced rate of relapse and progression to …

Pretreatment Characteristics Associated With Symptom Reduction During Group Cognitive Processing Therapy Versus Exposure Therapy For Ptsd: An Exploratory Study Of Veterans, Christopher Hunt, Brooks Casas, Pearl H Chiu, Lia J Smith, Laura Priorello, Kelly Lee, Matthew Estey, Mary R Newsome, M Wright Williams

Faculty, Staff and Students Publications

Exposure and cognitive-based therapies are both effective for PTSD, but knowledge of which intervention is best for which patient is lacking. This lack of knowledge is particularly noticeable for group treatments, as no study has examined whether responses to different group therapies are associated with different pretreatment characteristics. Here, we explored whether pretreatment levels of three types of psychological characteristics-PTSD symptom clusters, posttraumatic cognitions, and emotion regulation difficulties-were associated with symptom reduction during group-delivered cognitive versus exposure-based PTSD treatment. Participants were Veterans with PTSD drawn from two previous clinical trials: one of group CPT (GCPT;

Maladaptive Behaviors In Disasters: Case Study Evaluation Of Hurricane Hugo, Hurricane Katrina And The Haiti Earthquake, Andrew M Milsten, Christopher S Kang, Ira Nemeth

Faculty, Staff and Students Publications

Maladaptive behaviors during a disaster refer to actions that do not benefit the individual or society. Quarantelli highlights several maladaptive behaviors myths associated with disasters: widespread antisocial behavior, passivity, role conflict or abandonment, and sudden widespread mental health breakdowns (1). Despite early work reporting these myths, the common perception is that maladaptive behaviors such as rioting, looting, panic, and criminal conduct are prevalent in the wake of disasters. This is despite research by de Ville de Goyet and Arnold which has called on public officials and the media to stop propagating false disaster myths (2, 3). The classic academic response …

Management Advice For Patients With Reflux-Like Symptoms: An Evidence-Based Consensus, A Pali Hungin, Rena Yadlapati, Foteini Anastasiou, Albert J Bredenoord, Hashem El Serag, Pierluigi Fracasso, Juan M Mendive, Edoardo V Savarino, Daniel Sifrim, Mihaela Udrescu, Peter J Kahrilas

Faculty, Staff and Students Publications

Patients with reflux-like symptoms (heartburn and regurgitation) are often not well advised on implementing individualised strategies to help control their symptoms using dietary changes, lifestyle modifications, behavioural changes or fast-acting rescue therapies. One reason for this may be the lack of emphasis in management guidelines owing to 'low-quality' evidence and a paucity of interventional studies. Thus, a panel of 11 gastroenterologists and primary care doctors used the Delphi method to develop consolidated advice for patients based on expert consensus. A steering committee selected topics for literature searches using the PubMed database, and a modified Delphi process including two online meetings …

The Uterine Secretome Initiates Growth Of Gynecologic Tissues In Ectopic Locations, Jan Sunde, Morgan Wasickanin, Tiffany A Katz, Laurel Gillette, Sanam Bidadi, Derek O'Neil, Ramya Masand, Richard O Burney, Kathleen A Pennington

Faculty, Staff and Students Publications

Endosalpingiosis (ES) and endometriosis (EM) refer to the growth of tubal and endometrial epithelium respectively, outside of their site of origin. We hypothesize that uterine secretome factors drive ectopic growth. To test this, we developed a mouse model of ES and EM using tdTomato (tdT) transgenic fluorescent mice as donors. To block implantation factors, progesterone knockout (PKO) tdT mice were created. Fluorescent lesions were present after oviduct implantation with and without WT endometrium. Implantation was increased (p<0.05) when tdt oviductal tissue was implanted with endometrium compared to oviductal tissue alone. Implantation was reduced (p<0.0005) in animals implanted with minced tdT oviductal tissue with PKO tdT endometrium compared to WT endometrium. Finally, oviductal tissues was incubated with and without a known implantation factor, leukemia inhibitory factor (LIF) prior to and during implantation. LIF promoted lesion implantation. In conclusion, endometrial derived implantation factors, such as LIF, are necessary to initiate ectopic tissue growth. We have developed an animal model of ectopic growth of gynecologic tissues in a WT mouse which will potentially allow for development of new prevention and treatment modalities.

Optical Coherence Elastography Measures The Biomechanical Properties Of The Ex Vivo Porcine Cornea After Lasik, Achuth Nair, Fernando Zvietcovich, Manmohan Singh, Mitchell P Weikert, Salavat R Aglyamov, Kirill V Larin

Faculty, Staff and Students Publications

SIGNIFICANCE: The biomechanical impact of refractive surgery has long been an area of investigation. Changes to the cornea structure cause alterations to its mechanical integrity, but few studies have examined its specific mechanical impact.

AIM To quantify how the biomechanical properties of the cornea are altered by laser assisted in situ keratomileusis (LASIK) using optical coherence elastography (OCE) in ex vivo porcine corneas.

APPROACH: Three OCE techniques, wave-based air-coupled ultrasound (ACUS) OCE, heartbeat (Hb) OCE, and compression OCE were used to measure the mechanical properties of paired porcine corneas, where one eye of the pair was left untreated, and the …

Single Cell Analysis Of Short-Term Dry Eye Induced Changes In Cornea Immune Cell Populations, Jehan Alam, Ebru Yaman, Gerda Cristal Villalba Silva, Rui Chen, Cinita S De Paiva, Mary Ann Stepp, Stephen C Pflugfelder

Faculty, Staff and Students Publications

BACKGROUND: Dry eye causes corneal inflammation, epitheliopathy and sensorineural changes. This study evaluates the hypothesis that dry eye alters the percentages and transcriptional profiles of immune cell populations in the cornea.

METHODS: Desiccating stress (DS) induced dry eye was created by pharmacologic suppression of tear secretion and exposure to drafty low humidity environment. Expression profiling of corneal immune cells was performed by single-cell RNA sequencing (scRNA-seq). Cell differentiation trajectories and cell fate were modeled through RNA velocity analysis. Confocal microscopy was used to immunodetect corneal immune cells. Irritation response to topical neurostimulants was assessed.

RESULTS: Twelve corneal immune cell populations …

The Utility Of Software-Detected Non-Invasive Tear Break-Up In Comparison To Fluorescein Tear Break-Up Measurements, Stephen C Pflugfelder, Yasushi Kikukawa, Shin Tanaka, Takuya Kosugi

Faculty, Staff and Students Publications

PURPOSE: The purpose of this study is to characterize and discuss the difference between software-detected non-invasive tear break-up time (NIBUT) and the traditional clinical method of fluorescein break-up time (FBUT).

METHODS: Tear interferometry with the KOWA DR-1α (Kowa, Japan) and a standardized comprehensive ocular surface/tear evaluation were performed in 307 eyes. Software-detected NIBUT in the KOWA DR-1α images and the investigator-detected FBUT were compared.

RESULTS: Software-detected NIBUT was significantly shorter than investigator-measured FBUT. NIBUT was 3.1 ± 2.5 s (mean ± SD), whereas FBUT was 4.8 ± 3.0 s. This difference was due to three different patterns or conditions: a …