Synapses are specialized neural cell adhesions that underlie neurotransmission (Lynch, Rex, & Gall, 2007; Vicente-Manzanares, Hodges, & Horwitz, 2009). Synapse development is altered in the neurodevelopmental disorders of epilepsy, intellectual disability, and autism spectrum disorders (Forrest, Parnell, & Penzes, 2018). The onset of excitatory synapse formation occurs during mid-fetal gestation (Tierney & Nelson, 2009; Yuste & Bonhoeffer, 2004). Intriguingly, the expression profile of genes associated with neurodevelopmental disorders peaks in prenatal brain development (Birnbaum, Jaffe, Hyde, Kleinman, & Weinberger, 2014). However, due to our inability to image synaptogenesis in utero, prenatal brain development remains understudied. Instead, most research focuses on postnatal refinement of synaptic circuits. In order to research the molecular mechanisms of fetal synaptogenesis, we develop human cortical spheroids (HCSs). HCSs offer an unprecedented opportunity to observe the initial formation of excitatory synapses (Wilson & Newell-Litwa, 2018).
Few studies have attempted to quantify the variety, price, and consumer desirability of fruits and vegetables (F&Vs) across a diversity of cities. We implemented a market basket survey of F&Vs from December 2018 to February 2019 in middle-income neighborhoods of the following cities: Visakhapatnam, India; Kathmandu, Nepal; Addis Ababa, Ethiopia; Dar es Salaam, Tanzania; Mexico City, Mexico; Bangkok, Thailand; and Brookline, United States. The total variety of fruits ranged from 4.1 in Visakhapatnam to 17.3 in Brookline, and of vegetables from 6.1 in Dar es Salaam to 20.3 in Brookline. Of the 3 fruits for which price data were collected, apples tended to be the most expensive, and bananas the least expensive. For vegetables, capsicum tended to be the most expensive and eggplants the least expensive. Tablet-based market basket surveys are a useful tool for evaluating food environments. These pilot data provide further evidence of the homogenization of global diets.
The developing prenatal brain is particularly susceptible to environmental disturbances. During prenatal brain development, synapses form between neurons, resulting in neural circuits that support complex cognitive functions. In utero exposure to environmental factors such as pharmaceuticals that alter the process of synapse formation increases the risk of neurodevelopmental abnormalities. However, there is a lack of research into how specific environmental factors directly impact the developing neural circuitry of the human brain. For example, selective serotonin reuptake inhibitors are commonly used throughout pregnancy to treat depression, yet their impact on the developing fetal brain remains unclear. Recently, human brain models have provided unprecedented access to the critical window of prenatal brain development. In the present study, we used human neurons and cortical spheroids to determine whether the selective serotonin reuptake inhibitor fluoxetine alters neurite and synapse formation and the development of spontaneous activity within neural circuits. We demonstrate that cortical spheroids express serotonin transporter, thus recapitulating the early developmental expression of serotonin transporter associated with cortical pyramidal neurons. Cortical spheroids also appropriately express serotonin receptors, such as synaptic 5-HT2A and glial 5-HT5A. To determine whether fluoxetine can affect developing neural circuits independent of serotonergic innervation from the dorsal and medial raphe nuclei, we treated cortical neurons and spheroids with fluoxetine. Fluoxetine alters neurite formation in a dose-dependent fashion. Intriguingly, in cortical spheroids, neither acute nor chronic fluoxetine significantly altered excitatory synapse formation. However, only acute, but not chronic fluoxetine exposure altered inhibitory synaptogenesis. Finally, fluoxetine reversibly suppresses neuronal activity in a dose-dependent manner. These results demonstrate that fluoxetine can acutely alter synaptic function in developing neural circuits, but the effects were not long-lasting. This work provides a foundation for future studies to combine serotonergic innervation with cortical spheroids and assess the contributions of fluoxetine-induced alterations in serotonin levels to brain development.
West Virginia (WV) has the highest rates of obesity and cardiopulmonary disease in the United States (U.S.). Recent work has identified a significant care gap in WV for obstructive sleep apnea (OSA). This OSA care gap likely has significant health implications for the region given the high rates of obesity and cardiopulmonary disease. The purpose of this mix methods study was to identify barriers that contribute to the rural OSA care disparity previously identified in WV. Methods: This study used mixed methods to evaluate the barriers and facilitators to management of OSA at Federally Qualified Health Centers serving communities in southern WV. Focus groups were conducted at federally qualified health centers with providers serving Appalachian communities. Participants also completed the validated Obstructive Sleep Apnea Knowledge and Attitudes (OSAKA) questionnaire to gain insight into provider knowledge and beliefs regarding OSA. EMR analysis using diagnostic codes was completed at the sites to assess OSA prevalence rates. The same individual served as the interviewer in all focus group sessions to minimize interviewer variability/bias. Our team checked to ensure that the professional transcriptions were correct and matched the audio via spot checks. Results: Themes identified from the focus groups fell into three broad categories: (1) barriers to OSA care delivery, (2) facilitators to OSA care delivery, and (3) community-based care needs to optimize management of OSA in the targeted rural areas. Questionnaire data demonstrated rural providers feel OSA is an important condition to identify but lack confidence to identify and treat OSA. Evaluation of the electronic medical record demonstrates an even larger OSA care gap in these rural communities than previously described. Conclusion: This study found a lack of provider confidence in the ability to diagnose and treat OSA effectively and identified specific themes that limit OSA care in the communities studied. Training directed toward the identified knowledge gaps and on new technologies would likely give rural primary care providers the confidence to take a more active role in OSA diagnosis and management. An integrated model of care that incorporates primary care providers, specialists and effective use of modern technologies will be essential to address the identified OSA care disparities in rural WV and similar communities across the U.S. Community engaged research such as the current study will be essential to the creation of feasible, practical, relevant and culturally competent care pathways for providers serving rural communities with OSA and other respiratory disease to achieve health equity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.