6501 research outputs found
Sort by
LIPID NANOPARTICLES FOR GENE THERAPY AND IMMUNOMODULATION IN REPRODUCTIVE HEALTH
No full textNucleic acids are one of the most dynamic biomolecules capable of transiently controlling gene expression within cells to study and treat disease. Lipid nanoparticles (LNPs) are the most preclinically and clinically advanced nucleic acid delivery platforms with proven efficacy in delivering both siRNA and mRNA. This dissertation develops and applies LNPs specifically towards the treatment of reproductive diseases. First, we design an LNP formulation optimized for delivery to endometrial cancer cells using a systematic design process, establishing the first LNP platform developed for this application. Next, we develop LNPs for the delivery of IL-4 mRNA (IL-4-LNPs) and IL- 13 mRNA (IL-13-LNPs) to trophoblasts with the intent to control macrophage phenotype in the placenta. Finally, we develop two targeting strategies to increase placenta-specific delivery of LNP payloads. First, we surface-conjugated anti-plCSA antibody fragments (Fabs) to the surface of LNPs to promote cell-specific binding. Second, we developed a novel mRNA construct encoding a self-targeting IL-4 (HT-4) mRNA sequence delivered via LNPs, which overcomes challenges associated with ligand targeting. Our second and third objectives demonstrate that LNPs can target the placenta and release immunologically active payloads, towards the goal of local immunomodulation. Together, this dissertation presents new technologies and opportunities to use LNPs to treat reproductive diseases to improve outcomes for patients
The Challenges of Implementing and Documenting Ottawa Ankle Rules in the Pediatric Emergency Department: A Retrospective Study
Get PDFINTRODUCTIONAcute ankle sprains account for nearly 2% of visits to the pediatric emergency department (PED). The Ottawa Ankle Rules (OAR) were developed as a safe and effective clinical decision-making tool for detecting the need for radiographs in adults with acute ankle pain. OAR state radiographs are required with at least one of the following:
1. Inability to bear weight immediately following the injury and for four steps in the ED 2. Bony tenderness at the posterior edge of the lateral or medial malleolus
OBJECTIVEFew prospective cohort studies have attempted to assess OAR pediatric populations. This study investigates the validity and documentation of OAR within a single academic institution’s PED.
METHODS This retrospective chart review included previously healthy patients aged 2-19 years who presented to the PED with a traumatic ankle injury between 2019 and 2021. Exclusion criteria were met with documented parental insistence for imaging studies. We compared calculated OAR predictive values to those in literature using Chi-squared tests and WINPEPI.
RESULTS A total of 295 subjects were included. When only considering clinically significant fractures in the data analysis, 247 patients received X-rays and 42 clinically significant fractures were found. OAR were 100% sensitive (95% confidence interval 93.1–100.0), 12.2% specific (95% CI 8.2–17.2), with a positive predictive value (PPV) of 18.9% (95% CI 16.6–26.5), and negative predictive value (NPV) of 100% (95% CI 88.7–100.0). When comparing this study’s findings to those with similar design protocol, specificity was lower (p\u3c0.05) and there was no significant difference in sensitivity, PPV, or NPV.
CONCLUSION Implementing the highly sensitive OAR yielded zero missed fractures. Their poor specificity results in unnecessary radiation exposure, which also increases expense and wait time. Excess imaging may be attributed to ambiguous OAR criteria, their dependence on pediatric cooperation, and parental expectations for imaging studies
Classroom Routines to Support Inclusion and Engagement for First Gen Students
Get PDFThough First Generation Students are a diverse group, many of them encounter common challenges within the college setting. First Generation Students often worry that college education is not for them, that they do not belong, leading to feelings of loneliness, isolation and alienation. Social interactions can feel like a stressful test of suitability and belonging. This can threaten academic success, especially in classes that require discussion, participation, and risk-taking. This workshop seeks to support faculty in addressing these challenging feelings and supporting positive academic behaviors
Computer Aided Design of Aromatic Foldamer Targeting Protein-protein Interaction
Get PDFWith the computational tools developed in our lab for accurate prediction of structures and solution dynamics of aromatic foldamers, we now target protein-protein interaction (PPI) by appending proteinogenic side chains on the external surfaces of the helical aromatic foldamers. Particularly, the activation of a regulatory protein NF-κB, a key player in the inflammatory response and cell proliferation, involves binding of NEMO (NF-κB Essential Modulator) with linear di-ubiquitin. In this study, we designed various sequences based on established protocols and investigated, by utilizing molecular dynamics (MD) simulations, their potential binding to di-ubiquitin, specifically targeting the NEMO binding interface. This study complements experimental works related to synthesis, characterization, and crystallization of aromatic foldamers. Here, we present structural analysis of MD trajectories from simulations of 21 aromatic foldamers/di-ubiquitin systems with explicit solvent (aqueous) to gain insight into the binding interaction
Synthesis and Photopatterning of Synthetic Thiol-Norbornene Hydrogels
Get PDFHydrogels are a class of soft biomaterials and the material of choice for a myriad of biomedical applications due to their biocompatibility and highly tunable mechanical and biochemical properties. Specifically, light-mediated thiol-norbornene click reactions between norbornene-modified macromers and di-thiolated crosslinkers can be used to form base hydrogels amenable to spatial biochemical modifications via subsequent light reactions between pendant norbornenes in the hydrogel network and thiolated peptides. Macromers derived from natural sources (e.g., hyaluronic acid, gelatin, alginate) can cause off-target cell signaling, and this has motivated the use of synthetic macromers such as poly(ethylene glycol) (PEG). In this study, commercially available 8-arm norbornene-modified PEG (PEG-Nor) macromers were reacted with di-thiolated crosslinkers (dithiothreitol, DTT) to form synthetic hydrogels. By varying the PEG-Nor weight percent or DTT concentration, hydrogels with a stiffness range of 3.3 kPa–31.3 kPa were formed. Pendant norbornene groups in these hydrogels were used for secondary reactions to either increase hydrogel stiffness (by reacting with DTT) or to tether mono-thiolated peptides to the hydrogel network. Peptide functionalization has no effect on bulk hydrogel mechanics, and this confirms that mechanical and biochemical signals can be independently controlled. Using photomasks, thiolated peptides can also be photopatterned onto base hydrogels, and mesenchymal stem cells (MSCs) attach and spread on RGD-functionalized PEG-Nor hydrogels. MSCs encapsulated in PEG-Nor hydrogels are also highly viable, demonstrating the ability of this platform to form biocompatible hydrogels for 2D and 3D cell culture with user-defined mechanical and biochemical properties
Mean Flow and Dispersion in the Western Mediterranean Sea from Drifter Observations
Get PDFCurrents in the ocean distribute water masses and everything floating in them. To understand how fast the water (and its flotsam) travels and how effectively it mixes, we need to study the flow statistics. There are two types of measurements of ocean currents: Eulerian measurements that look at how the ocean velocities change at a stationary point on the Earth; and Lagrangian measurements that follow a water mass. Dispersion and mixing is generally best captured by Lagrangian measurements. At the submesoscale (~10-1 – 10 km), the observational tool of choice are drifters, or floating buoys, tethered to a drogue that ensures the drifter moves with the water masses at a particular depth. Here we report on the flow statistics from a particularly rich drifter dataset collected in the Western Mediterranean Sea over 3 years, in different seasons and at different depths
Implementation of rapid genomic sequencing in safety-net neonatal intensive care units: protocol for the VIrtual GenOme CenteR (VIGOR) proof-of-concept study.
Get PDFINTRODUCTION: Rapid genomic sequencing (rGS) in critically ill infants with suspected genetic disorders has high diagnostic and clinical utility. However, rGS has primarily been available at large referral centres with the resources and expertise to offer state-of-the-art genomic care. Critically ill infants from racial and ethnic minority and/or low-income populations disproportionately receive care in safety-net and/or community settings lacking access to state-of-the-art genomic care, contributing to unacceptable health equity gaps. VIrtual GenOme CenteR is a \u27proof-of-concept\u27 implementation science study of an innovative delivery model for genomic care in safety-net neonatal intensive care units (NICUs).
METHODS AND ANALYSIS: We developed a virtual genome centre at a referral centre to remotely support safety-net NICU sites predominantly serving racial and ethnic minority and/or low-income populations and have limited to no access to rGS. Neonatal providers at each site receive basic education about genomic medicine from the study team and identify eligible infants. The study team enrols eligible infants (goal n of 250) and their parents and follows families for 12 months. Enrolled infants receive rGS, the study team creates clinical interpretive reports to guide neonatal providers on interpreting results, and neonatal providers return results to families. Data is collected via (1) medical record abstraction, (2) surveys, interviews and focus groups with neonatal providers and (3) surveys and interviews with families. We aim to examine comprehensive implementation outcomes based on the Proctor Implementation Framework using a mixed methods approach.
ETHICS AND DISSEMINATION: This study is approved by the institutional review board of Boston Children\u27s Hospital (IRB-P00040496) and participating sites. Participating families are required to provide electronic written informed consent and neonatal provider consent is implied through the completion of surveys. The results will be disseminated via peer-reviewed publications and data will be made accessible per National Institutes of Health (NIH) policies.
TRIAL REGISTRATION NUMBER: NCT05205356/clinicaltrials.gov
Unplanned Pregnancy as an Independent Risk Factor for Antepartum SI in a Post Roe vs. Wade World
Get PDFAbstract: The objective of this literature review is to determine whether unplanned pregnancy is an independent risk factor for developing antepartum SI. Background: The Supreme Court of the United States of America recently ruled that the constitution of the United States does not confer a right to abortion to its citizens. As of October 2023, twenty-one states had developed full or partial bans on abortion, resulting in millions of Americans residing in areas where terminating unplanned pregnancy is not a viable option. There is evidence that indicates antepartum suicidal ideation (SI) is higher than that of the general population, however the rate of completion of antepartum suicide is lower than that of the general population4. Risk factors for antepartum SI are important to identify for early intervention, and it is now more vital than ever to understand how the U.S.’s reproductive health landscape may contribute to these risk factors. Methods: This literature review utilized the databases PubMed, and PsycINFO as queries for primary data. Inclusion criteria included written in the English language, peer-reviewed, methodology of cross-sectional or longitudinal study design, and published between 2003 and 2023. Studies were excluded based on relevance, with articles focused on postpartum SI/depression, suicidal action/self-harm, and antepartum SI associated with specific medical conditions/medications excluded. Results: A total of 6 studies were included in this literature review with incidence rates of antepartum SI ranging from 1.3% to 27.8%. Independent risk factors for antepartum SI that were identified across multiple studies were: history of depression or other psychiatric disorders; partner violence or marital problems; and belonging to a racial or ethnic minority. Unplanned pregnancy failed to be established as an independent risk factor for antepartum SI. Discussion: While unplanned pregnancy was not found to be an independent risk factor in this study, it has the potential to contribute to likelihood of developing antepartum SI in patients with already established independent risk factors. The major limitation of this study was the lack of literature regarding the risk of developing SI during pregnancy and relating that risk to unplanned pregnancy, as well as the lack of literature conducted after the Dobbs vs. Jackson Women’s Health decision. As the Dobbs vs. Jackson Women’s Health decision affects more pregnant Americans, it is important that we continue to monitor our pregnant patients for signs and symptoms of SI and to continue to examine potential risk factors
Splenic Artery Aneurysm Masquerading as Chest Pain: A Case Report of a Rare Clinical Presentation
Get PDFBackground: Splenic artery aneurysms most commonly present with vague epigastric or left upper quadrant abdominal pain that may radiate to the left shoulder. Chest pain associated with splenic artery aneurysm is an unusual phenomena. This case presents a rare occurrence of a splenic artery aneurysm originally presenting as atypical chest pain. Case Presentation: A 46 year old G3P2 AAF patient with family history of hypertension presented to the ER with pleuritic left chest pain, episodes of shortness of breath, and new onset hypertension. Chest x-ray and ECG were unremarkable. Pertinent labs included a hemoglobin of 10.6 and D-dimer of 4.10. CTA of the chest revealed no evidence of pulmonary embolism. Bilateral ultrasound of the lower extremities was negative for deep vein thrombosis. Following her negative workup, the patient’s symptoms were presumed to be related to allergies or asthma, although there was no symptomatic improvement with albuterol inhaler. Following discharge, the patient’s symptoms persisted and began to present as left upper quadrant abdominal pain with fullness. CT of the abdomen and pelvis with and without contrast revealed a large lobular mass in the left upper quadrant with unknown origin. Open exploratory laparoscopy surprisingly revealed a splenic artery aneurysm that had recently ruptured. The patient underwent distal pancreatectomy, splenectomy, and adrenalectomy during this operation. Conclusion: Although the presentation of a splenic artery aneurysm as chest pain is rare, evaluation for this pathology may be indicated in patients with new onset left chest pain, hematologic abnormalities, and negative pulmonary/cardiac workup
The Effect of COVID-19 Pandemic on Sanitation Practices and Anxiety in the General Population
Get PDFBackground: Illness anxiety and fear of contracting coronavirus increased considerably during the COVID-19 pandemic. The media, being in lockdown, and cyberchondria had the largest impact on the population’s anxiety surrounding illness. While this kind of reaction to illness is expected during the pandemic, there is limited data on post-pandemic illness anxiety levels in the general population. Patients’ perception of disease impacts medicine at every level; medical professionals need to understand the concerns and fears of their patients in order to treat the post-pandemic patient. We hypothesized that sanitation practices and anxiety surrounding illness have not returned to baseline pre-COVID-19 pandemic levels.
Methods: A 26-question survey was designed and distributed via Qualtrics. The questions included demographic information, sanitation practices, and illness anxiety levels pre- and post-pandemic. Participants were recruited in-person at Rowan-Virtua Family Medicine Offices. They were given the option to take the survey on their personal device using a QR code to access the survey or complete the survey in Qualtrics using the researcher’s laptop. All participants chose to complete the survey in Qualtrics using the researcher’s laptop.
Results: The study analyzed fifty-five responses using SPSS. Paired t-test for hand sanitizing and masking pre- and post-pandemic showed significant results (p= 0.001) towards a decline in these behaviors post-pandemic. Concern for contracting COVID-19 also decreased post-pandemic (p= 0.001). Furthermore, female identifying participants were more likely to make an appointment to see their physician if they develop a new symptom (p= 0.026). Lastly, 87% of participants were vaccinated for COVID-19 and 71% of participants received at least one booster. There was no statistically significant difference between ethnicity and illness anxiety post-pandemic.
Conclusion: Illness anxiety levels and sanitation practices have returned to pre-pandemic baseline