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Changes in Address and the Child Opportunity Index after Delivery in a Cohort of First-time Mothers
Get PDFBackground: The Child Opportunity Index (COI) characterizes social determinants of health across the United States including education, health and environment, and social and economic factors. The objective of the study was to determine if the nulliparous pregnant persons changed addresses between the time of delivery and at the time of follow-up 9-11 years after delivery and to evaluate the trajectory of the COI over time.
Methods: We analyzed data from nulliparous pregnant people participating in the nuMoM2b Heart Health follow-up Study (HHS). Residential addresses at delivery and at follow-up (~9 years) were compared to determine if the participant changed addresses and to evaluate the COI trajectory. Descriptive characteristics (age, race, income, pregnancy outcomes) and the COI trajectory were compared for those who did and did not move using chi-square and t-tests.
Results: 410 participants were analyzed. 304 (74%) of the participants changed addresses resulting in changes in census tracts. Moving was associated with a lower mean maternal age (24.3 vs. 27.2 yrs, p≤0.001) and a lower average income (62.3% vs 41.1% <200% FPL,p≤0.001) compared to the participants who did not move. 40.5% moved to a neighborhood with a higher COI quintile, 56 (18.4%) participants moved down a COI quintile, and 125 (41.1%) participants did not have a change in COI category. White participants who moved addresses were significantly more likely to increase their COI category (55%) compared to non-White participants who moved addresses (22.2%, p≤0.001). There were no differences in how COI changed between White and non-White participants who did not move.
Conclusion: The majority of the participants moved in the years after delivering their first child. Moving was typically associated with an improvement in COI categories, with disparities seen as White participants were more likely to increase their COI if they moved compared to non-White groups
Tobacco smoking and early onset cataracts
Get PDFBackground and Hypothesis:Cataracts are among the leading causes of blindness in the world. Smoking tobacco has been linked to cataract formation in old age. However, its linkage in causing an earlier onset is much more questionable. Assessing this linkage can help identify risk factors and help understand the causes and pathogenesis in development of cataracts over time. This can help direct modifiable risk factors in patients to prevent early deterioration in health, finance, physical capabilities, and overall comfort. It is hypothesized that history and intensity of smoking tobacco correlates with earlier onset cataracts.
Experimental Design or Project Methods:Patient data of patients aged 40-65 were gathered from the last two years of cataract surgeries from Deen-Gross Eye Centers EMR (n=718). Age at date of surgery was used as observed value for determining earlier onset, and pre-operation charts were used to collect patient data on smoking status (light, someday, every day, heavy, former, never), age, gender, hypertension, diabetes, number of eyes operated on, family history (cataracts/glaucoma), and glaucoma. Statistical analysis was performed among the gathered data.
Results:Statistical analysis revealed no significant difference in the ages of cataract surgeries between smokers and non-smokers. Controlling for non-hypertensive and non-diabetic patients revealed a similar result. There was no significant difference in smoking status between ages 40-55 and ages 56-65 who underwent surgery. There was no significant difference in age of surgery among each of the individual types of smokers.
Conclusion:No significant associations were found. This calls for further research to better understand the linkage between tobacco smoking and cataracts, as well as the pathogenesis of earlier onset cataracts. No modifications in directing patient care can be made yet
A Molecular Dynamics Investigation of Ligand-Mediated PPARγ Transrepression
Get PDFBackground and Hypothesis: PPARγ is a nuclear receptor expressed in most cells of the body and exerts metabolic function, including adipocyte differentiation and insulin sensitization. This mechanism is termed transactivation, where ligand binding leads to transcription of target genes. However, PPARγ also has a transrepression activity, where ligand binding inhibits other transcriptional pathways, leading to regulation of the immune system. While the molecular mechanisms of transactivation are well understood, there is little research on the mechanisms of transrepression. Previous studies have implied that these activity states act independently and can be selected for in small molecule design campaigns, but this has yet to be accomplished. Therefore, the aim of this project was to investigate if distinct molecular interactions exist between PPARγ transactivation versus transrepression using a combined computational and structural biology approach.
Methods: Molecular dynamics (MD) simulations were performed using the CHARMM molecular modeling software to produce 300 ns simulations of PPARγ-ligand complexes. Simulations were analyzed to identify potential protein-ligand interactions, and distances were measured between atoms of interest and compared.
Results: Although PPARγ’s binding site is large, structural analyses showed that most ligands remained near their initial starting position within the binding pocket throughout an MD simulation. Starting coordinates were taken from previously solved crystal structures or via manual docking based on molecular similarities. Four residues were identified to consistently interact with most of the ligands: Arg280, Ser342, Glu259, and Cys285. These residues differ from previously reported interactions associated with PPARγ transactivation.
Conclusion: Our results suggest that these residues may play a role in PPARγ transrepression, but these conclusions are preliminary and should be confirmed through further investigation. Future research would include performing replicate simulations and mutational analyses to further explore the involvement of these residues in PPARγ transrepression. Additional PPARγ ligands should also be explored
The Effects of Extracellular Matrix Allograft Administration on Knee Inflammation Following an Anterior Cruciate Ligament Injury in Mice
Get PDFBackground and Hypothesis:A human placental-derived extracellular matrix (ECM) allograft has previously been developed and is indicated by the manufacturer for reducing tissue inflammation and accelerated repair. To evaluate the efficacy of this product for reducing post-anterior cruciate ligament (ACL) injury inflammation, we used a novel murine in vivo ACL injury model. This model has previously been shown to induce significant synovitis, infrapatellar fat pad (IFP) fibrosis, and articular cartilage (AC) degradation within 2 weeks following an ACL injury. We hypothesized that intra-articular injections of the allograft would correspond with a decrease in synovitis, fibrosis, and articular cartilage degradation.
Experimental Design or Project Methods:Ten-week-old C57BL/6J mice were randomly placed into 4 groups (n=10/group). For all mice, the right ACL was ruptured. One group served as sham controls, with a single intra-articular saline injection 24-hours following injury. The remaining three groups received 1, 2, and 6 allograft injections respectively beginning 24-hours after injury. Mice were euthanized 14 days after injury. Following euthanasia, the degree of IFP fibrosis, knee synovitis, and AC degradation were histopathologically evaluated.
Results:Thus far, 5 mice per group have been analyzed. Within this subset of mice, those that received 6 injections demonstrated a significantly higher synovitis score (p < 0.01) than the sham group. The 1-injection (p < 0.01), 2-injection (p = 0.16), and 6-injection (p = 0.03) groups each displayed greater IFP fibrosis, relative to sham. No significant differences were found in AC degeneration across groups.
Conclusion and Potential Impact:If the current results hold, following the analyses of the remaining mice, then this particular orthobiologic may not be suitable for reducing the post-ACL injury inflammatory response in mice. However, there are several limitations to this pilot study that will first need to be accounted for to confirm the lack of efficacy found
Expanding Social Work Licensure to Strengthen the Homelessness Service Workforce
Get PDFHomeless services require appropriate funding, access to necessary resources, and experienced staff to effectively connect individuals to housing and services with a Housing First lens. This policy brief examines part of the solution to the third requirement: trained and experienced staff. The brief proposes two state-level legislative changes to expand social work licensure access. Through the elimination of a social work licensure exam and the expansion of licensing to non-degree holders, the workforce supporting homelessness services can reflect the population being served. It will reduce historic racial disparity in licensure access, increase salaries for service providers, and allow for BIPOC leaders to step into supervisory roles with more ease
Table Talk: Insights from the Statewide Conference
Get PDFConference attendees responded to prompts about IU and community
Investigating the Functional Impacts of Metabolic Disease Associated Immune-Vascular Interactions in Alzheimer’s Disease
Get PDFBackground and Hypothesis:Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder with undefined etiology and is the fifth leading cause of death worldwide. AD pathology is characterized by amyloid-beta (Aβ) plaques. Previous work demonstrated that alterations in the microvasculature are some of the earliest recognizable changes in AD, and that most patients with dementia have mixed vascular pathologies. We investigated the functional impacts of metabolic disease associated immune-vascular perturbation on the underlying mechanisms of AD.
Methods:Adult male Leprdb/J (db/db) were obtained from the Jackson Laboratory. Activated microglia and brain vessel density levels were assessed using immunofluorescence. Cerebral microvessels were isolated for RNA examination using qPCR, and FACS-based analysis of brain endothelial cells. Immunofluorescence of hAβ42 transport in microvessels were observed via confocal microscope. Quantification of images were performed using Fiji (NIH) software.
Results:Db/db mice brains displayed higher levels of activated microglia with increased soma area and decreased circularity (p<0.05). This confirms early vascular stress leads to increased immune cell activation. Brain vessel density analysis revealed a non-statistically significant trend with decreased density in db/db mice. Given that functional changes occur before structural changes, we shifted our examination to the microvasculature. Brain microvessels were isolated and validated and both qPCR and FACS results demonstrated increased levels of inflammatory mediators and cell adhesion molecules in db/db mice (p<0.05), confirming microvessel dysfunction and neuroinflammation. Finally, quantification of luminal area fluorescence demonstrated decreased hAβ42 transport in db/db mice (p<0.01), validating functional disturbance in the cerebral microvasculature.
Conclusion and Impact:The vascular risk factors of metabolic disease can lead to dysfunction and inflammation in cerebral microvasculature, causing accelerated progression of AD. Our results emphasize the contributory role of cerebral small vessel health in the origin and evolution of AD and present an opportunity for novel development of surrogate biomarkers and therapeutic treatments
Novel Method for Development of Nanobubbles with Consistent Size Distribution
Get PDFBackground/Objective:Ultrasound is a versatile non-invasive clinical tool that can be used for monitoring, diagnosis, and management of disease. Contrast-Enhanced Ultrasound (CEUS) takes advantage of microbubbles which are small gas filled bubbles made of lipids to image and evaluate functioning of organs such as the heart, liver, and kidneys. CEUS is better for assessing vascularization of tissues compared to US. However, ultrasound contrast agents have been limited by their size and cannot extravasate blood vessels easily. Current methods also have high polydispersity. We hypothesize that a microfluidic device could deliver nanobubbles with improved size distribution by mixing through micro sized pores.
Methods:The microfluidic device was fabricated using 3D printing for a proof of concept and photolithography for functional use and was done in a class 1-10-100-1000 cleanroom. SU-8 photoresist was spun onto a 4” silicon wafer at 3000 rpm for 30 seconds. The silicon wafer was then baked and exposed under UV with a photomask designed on AutoCAD. The wafer was then developed, hard baked, and was cross linked with Polydimethylsiloxane (PDMS).
Results:Dynamic light scattering data of a shaken formulation shows a monodisperse distribution. Further work will have to be done to determine if this can be delivered by microfluidic device and the parameters that affect size and polydispersity.
Conclusion and Potential Impact:This study will determine the parameters needed for the microfluidic device to efficiently create microbubbles for contrast enhanced ultrasound