The impacts of anxiety and depression on outcomes in orthopaedic trauma surgery: a narrative review.

Introduction: The impact of anxiety and depression on outcomes in orthopaedic trauma surgery is a topic of growing research interest. Patients and methods: Orthopaedic trauma patients often experience high rates of psychiatric disorders, with anxiety and depression being the most prevalent. Mental health disorders have been shown to increase the risk of negative surgical outcomes and morbidity. This narrative review seeks to summarize the current literature surrounding the impacts of anxiety and depression on orthopaedic trauma surgery outcomes. Discussion: There is a bidirectional relationship between chronic pain and mental health disorders, involving overlapping brain regions and neurotransmitter pathways. Anxiety and depression have been identified as predictors of negative surgical outcomes in orthopaedic trauma patients. Screening tools like the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Screener-7 (GAD-7), and Medical Outcomes Study 36-item Short Form (SF-36) can assess mental health status and help tailor interventions. Psychological distress, chronic pain, and traumatic limb amputation are factors that contribute to adverse mental health outcomes in orthopaedic trauma patients. Opioid use for pain management is common in orthopaedic surgery, but it can worsen symptoms of depression and lead to dependency. Non-opioid pain management strategies may improve postoperative outcomes by reducing the impact of opioid-exacerbated depression. Conclusion: Mental health interventions, both preoperative and postoperative, are crucial in optimizing surgical outcomes and improving patient quality of life. Multidisciplinary approaches that address both physical and mental health are recommended for orthopaedic trauma patients. Further research is needed to develop effective interventions for improving mental health outcomes in this patient population.

Circadian rhythms in the blood-brain barrier: impact on neurological disorders and stress responses.

Circadian disruption has become more prevalent in society due to the increase in shift work, sleep disruption, blue light exposure, and travel via different time zones. The circadian rhythm is a timed transcription-translation feedback loop with positive regulators, BMAL1 and CLOCK, that interact with negative regulators, CRY and PER, to regulate both the central and peripheral clocks. This review highlights the functions of the circadian rhythm, specifically in the blood-brain barrier (BBB), during both healthy and pathological states. The BBB is a highly selective dynamic interface composed of CNS endothelial cells, astrocytes, pericytes, neurons, and microglia that form the neurovascular unit (NVU). Circadian rhythms modulate BBB integrity through regulating oscillations of tight junction proteins, assisting in functions of the NVU, and modulating transporter functions. Circadian disruptions within the BBB have been observed in stress responses and several neurological disorders, including brain metastasis, epilepsy, Alzheimer's disease, and Parkinson's disease. Further understanding of these interactions may facilitate the development of improved treatment options and preventative measures.

Circadian disruption alters gut barrier integrity via a ß-catenin-MMP-related pathway.

We evaluated the mechanistic link between circadian rhythms and gut barrier permeability. Mice were subjected to either constant 24-h light (LL) or 12-h light/dark cycles (LD). Mice housed in LL experienced a significant increase in gut barrier permeability that was associated with dysregulated ß-catenin expression and altered expression of tight junction (TJ) proteins. Silencing of ß-catenin resulted in disruption of barrier function in SW480 cells, with ß-catenin appearing to be an upstream regulator of the core circadian components, such as Bmal1, Clock, and Per1/2. In addition, ß-catenin silencing downregulated ZO-1 and occludin TJ proteins with only limited or no changes at their mRNA levels, suggesting post transcriptional regulation. Indeed, silencing of ß-catenin significantly upregulated expression of matrix metallopeptidase (MMP)-2 and MMP-9, and blocking MMP-2/9 activity attenuated epithelial disruption induced by ß-catenin silencing. These results indicate the regulatory role of circadian disruption on gut barrier integrity and the associations between TJ proteins and circadian rhythms, while demonstrating the regulatory role of ß-catenin in this process.

Extracellular vesicles regulate gap junction-mediated intercellular communication and HIV-1 infection of human neural progenitor cells.

Human immunodeficiency virus-1 (HIV-1) has been shown to cross the blood-brain barrier and cause HIV-associated neurocognitive disorders (HAND) through a process that may involve direct or indirect interactions with the central nervous system (CNS) cells and alterations of amyloid ß (Aß) homeostasis. The present study focused on the mechanisms of HIV-1 infecting human neural progenitor cells (hNPCs) and affecting NPC intercellular communications with human brain endothelial cells (HBMEC). Despite the lack of the CD4 receptor, hNPCs were effectively infected by HIV-1 via a mechanism involving the chemokine receptors, CXCR4 and CCR5. HIV-1 infection increased expression of connexin-43 (Cx43), phosphorylated Cx43 (pCx43), and pannexin 2 (Panx2) protein levels in hNPCs, suggesting alterations in gap-junction (GJ) and pannexin channel communication. Indeed, a functional GJ assay indicated an increase in communication between HIV-infected hNPCs and non-infected HBMEC. We next analyzed the impact of HBMEC-derived extracellular vesicles (EVs) and EVs carrying Aß (EV-Aß) on the expression of Cx43, pCx43, and Panx2 in HIV-1 infected and non-infected hNPCs. Exposure to EV-Aß resulted in significant reduction of Cx43 and pCx43 protein expression in non-infected hNPCs when compared to EV controls. Interestingly, EV-Aß treatment significantly increased levels of Cx43, pCx43, and Panx2 in HIV-1-infected hNPCs when compared to non-infected controls. These results were confirmed in a GJ functional assay and an ATP release assay, which is an indicator of connexin hemichannel and/or pannexin channel functions. Overall, the current study demonstrates the importance of hNPCs in HIV-1 infection and indicates that intercellular communications between infected hNPCs and HBMEC can be effectively modulated by EVs carrying Aß as their cargo.