Gamma secretase activity modulates BMP-7-induced dendritic growth in primary rat sympathetic neurons.

Autonomic dysfunction has been observed in Alzheimer's disease (AD); however, the effects of genes involved in AD on the peripheral nervous system are not well understood. Previous studies have shown that presenilin-1 (PSEN1), the catalytic subunit of the gamma secretase (γ-secretase) complex, mutations in which are associated with familial AD function, regulates dendritic growth in hippocampal neurons. In this study, we examined whether the γ-secretase pathway also influences dendritic growth in primary sympathetic neurons. Using immunoblotting and immunocytochemistry, molecules of the γ-secretase complex, PSEN1, PSEN2, PEN2, nicastrin and APH1a, were detected in sympathetic neurons dissociated from embryonic (E20/21) rat sympathetic ganglia. Addition of bone morphogenetic protein-7 (BMP-7), which induces dendrites in these neurons, did not alter expression or localization of γ-secretase complex proteins. BMP-7-induced dendritic growth was inhibited by siRNA knockdown of PSEN1 and by three γ-secretase inhibitors, γ-secretase inhibitor IX (DAPT), LY-411575 and BMS-299897. These effects were specific to dendrites and concentration-dependent and did not alter early downstream pathways of BMP signaling. In summary, our results indicate that γ-secretase activity enhances BMP-7 induced dendritic growth in sympathetic neurons. These findings provide insight into the normal cellular role of the γ-secretase complex in sympathetic neurons.

Treatment of Dyslipidemia through Targeted Therapy of Gut Microbiota.

Dyslipidemia is a multifaceted condition with various genetic and environmental factors contributing to its pathogenesis. Further, this condition represents an important risk factor for its related sequalae including cardiovascular diseases (CVD) such as coronary artery disease (CAD) and stroke. Emerging evidence has shown that gut microbiota and their metabolites can worsen or protect against the development of dyslipidemia. Although there are currently numerous treatment modalities available including lifestyle modification and pharmacologic interventions, there has been promising research on dyslipidemia that involves the benefits of modulating gut microbiota in treating alterations in lipid metabolism. In this review, we examine the relationship between gut microbiota and dyslipidemia, the impact of gut microbiota metabolites on the development of dyslipidemia, and the current research on dietary interventions, prebiotics, probiotics, synbiotics and microbiota transplant as therapeutic modalities in prevention of cardiovascular disease. Overall, understanding the mechanisms by which gut microbiota and their metabolites affect dyslipidemia progression will help develop more precise therapeutic targets to optimize lipid metabolism.

Alternatives to Arrest for Illicit Opioid Use: A Joint Criminal Justice and Healthcare Treatment Collaboration.

Opioid overdoses continue to be a leading cause of death in the US. This public health crisis warrants innovative responses to help prevent fatal overdose. There is continued advocacy for collaborations between public health partners to create joint responses. The high correlation between persons with opioid use disorder who have a history of involvement in the criminal justice system is widely recognized, and allows for treatment intervention opportunities. Law enforcement-led treatment initiatives are still relatively new, with a few sparse early programs emerging almost a decade ago and only gaining popularity in the past few years. A lack of published methodologies creates a gap in the knowledge of applied programs that are effective and can be duplicated. This article seeks to outline an interagency relationship between police and healthcare that illustrates arrest is not the only option that law enforcement may utilize when encountering persons who use illicit substances. Program methods of a joint initiative between law enforcement and healthcare in a large, metropolitan area will be reviewed, supplemented with law enforcement overdose data and statistics on law enforcement treatment referrals.

Ankyloglossum Superius Syndrome compromising a neonatal airway: Considerations in congenital oral airway obstructions.

We report the case of a 37-week old newborn presenting on day 1 of life with an apparent congenital fusion of the tongue to the hard palate, consistent with Ankyloglossum Superius syndrome. Physical exam along with endoscopy showed apparent fusion of the floor of the mouth to the anterior hard palate displacing the tongue into the nasal cavity and obstructing the oral airway. The child was nasotracheally intubated and brought to the operating room for lysis of the fusion under binocular microscopy. We review the literature on this rare condition and provide an algorithm for evaluating the neonatal airway in the setting of congenital oral abnormalities.