Targeting Gut Dysbiosis and Microbiome Metabolites for the Development of Therapeutic Modalities for Neurological Disorders.

The gut microbiota, composed of numerous species of microbes, works in synergy with the various organ systems in the body to bolster our overall health and well-being. The most well-known function of the gut microbiome is to facilitate the metabolism and absorption of crucial nutrients, such as complex carbohydrates, while also generating vitamins. In addition, the gut microbiome plays a crucial role in regulating the functioning of the central nervous system (CNS). Host genetics, including specific genes and single nucleotide polymorphisms (SNPs), have been implicated in the pathophysiology of neurological disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), and autism spectrum disorder (ASD). The gut microbiome dysbiosis also plays a role in the pathogenesis of these neurodegenerative disorders, thus perturbing the gut-brain axis. Overproduction of certain metabolites synthesized by the gut microbiome, such as short-chain fatty acids (SCFAs) and p-cresyl sulfate, are known to interfere with microglial function and trigger misfolding of alpha-synuclein protein, which can build up inside neurons and cause damage. By determining the association of the gut microbiome and its metabolites with various diseases, such as neurological disorders, future research will pave the way for the development of effective preventive and treatment modalities.

Cytokine Profiling of Cyst Fluid and Tumor-Associated Macrophages in Cystic Vestibular Schwannoma.

BACKGROUND: The vestibular schwannoma (VS) secretome can initiate monocyte recruitment and macrophage polarization to M1 (proinflammatory) and/or M2 (protumorigenic) phenotypes, which in turn secrete additional cytokines that contribute to the tumor microenvironment. Profiling cyst fluid and cerebrospinal fluid (CSF) in cystic VS provides a unique opportunity to understand mechanisms that may contribute to tumor progression and cyst formation. HYPOTHESIS: Cystic VSs secrete high levels of cytokines into cyst fluid and express abundant M1 and M2 macrophages. METHODS: Tumor, CSF, and cyst fluid were prospectively collected from 10 cystic VS patients. Eighty cytokines were measured in fluid samples using cytokine arrays and compared with normal CSF from normal donors. Immunofluorescence was performed for CD80 + M1 and CD163 + M2 macrophage markers. Demographic, audiometric, and radiographic information was obtained through retrospective chart review. RESULTS: Cyst fluid expressed more osteopontin and monocyte chemotactic protein-1 (MCP-1; p < 0.0001), when compared with normal CSF. Cyst fluid also expressed more protein ( p = 0.0020), particularly MCP-1 ( p < 0.0001), than paired CSF from the same subjects. MCP-1 expression in cyst fluid correlated with CD80 + staining in VS tissue ( r = 0.8852; p = 0.0015) but not CD163 + staining. CONCLUSION: Cyst fluid from cystic VS harbored high levels of osteopontin and MCP-1, which are cytokines important in monocyte recruitment and macrophage polarization. MCP-1 may have a significant role in molding the tumor microenvironment, by polarizing monocytes to CD80 + M1 macrophages in cystic VS. Further investigations into the role of cytokines and macrophages in VS may lead to new avenues for therapeutic intervention.

Patient income level and health insurance correlate with differences in health care utilization during the COVID-19 pandemic.

Background: With the coronavirus outbreak of 2019 (COVID-19) came many changes in how health care is accessed and delivered. Perhaps most notable is the massive expansion of telemedicine, especially in the developed world. With pandemic-induced economic and health care system disruptions, it is reasonable to expect changes in how health care services are utilized by different patients. We examined how health care service usage trends changed for various patient demographics from the pre-COVID-19 era to the COVID-19 era. Design and methods: De-identified patient demographics and telemedicine, in-patient, in-person out-patient, radiology/procedures, and emergency department visit data (N = 1,164,719) between January 1st, 2019 and May 31st, 2021 were obtained from UHealth in Miami, Florida, USA. This cross-sectional study employed descriptive statistics and other tools to determine relationships between patient demographics and health system usage. Results: There were significant changes in health care usage and demographics for UHealth services from the pre-COVID-19 era to the COVID-19 era. There was an increase in telehealth visits and a corollary decrease of in-person out-patient visits (p < 0.001) along with increased health care utilization by those with commercial insurance (p < 0.001) during COVID-19. Lower-income patients had increased use of in-person out-patient services (p < 0.001). Non-Hispanic, English-speaking patients and those with higher median incomes had higher telemedicine usage. Conclusions: COVID-19 revealed differences in health care access, particularly telemedicine access, and highlighted differences in vulnerability among patient demographics. These trends are likely multifactorial and reflect changes in patients' preferences and disparities in care access.