Molecular Basis of Cerebral Vasospasm: What Can We Learn from Transcriptome and Temporal Gene Expression Profiling in Intracranial Aneurysm?

Cerebral vasospasm (CV) is a significant complication following aneurysmal subarachnoid hemorrhage (aSAH), and lacks a comprehensive molecular understanding. Given the temporal trajectory of intracranial aneurysm (IA) formation, its rupture, and development of CV, altered gene expression might be a molecular substrate that runs through these clinical events, influencing both disease inception and progression. Utilizing RNA-Seq, we analyzed tissue samples from ruptured IAs with and without vasospasm to identify the dysregulated genes. In addition, temporal gene expression analysis was conducted. We identified seven dysregulated genes in patients with ruptured IA with vasospasm when compared with those without vasospasm. We found 192 common genes when the samples of each clinical subset of patients with IA, that is, unruptured aneurysm, ruptured aneurysm without vasospasm, and ruptured aneurysm with vasospasm, were compared with control samples. Among these common genes, TNFSF13B, PLAUR, OSM, and LAMB3 displayed temporal expression (progressive increase) with the pathological progression of disease that is formation of aneurysm, its rupture, and consequently the development of vasospasm. We validated the temporal gene expression pattern of OSM at both the transcript and protein levels and OSM emerges as a crucial gene implicated in the pathological progression of disease. In addition, RSAD2 and ATP1A2 appear to be pivotal genes for CV development. To the best of our knowledge, this is the first study to compare the transcriptome of aneurysmal tissue samples of aSAH patients with and without CV. The findings collectively provide new insights on the molecular basis of IA and CV and new leads for translational research.

Proteomic-based identification of APCS as candidate protein for diagnosis of patients exhibiting anti-tubercular drug induced liver injury.

Traditional markers evaluate anti-tubercular drug-induced liver injury (AT-DILI). However, these markers have certain limitations and studies are in progress to characterize AT-DILI at an early stage. In the present study, 40 patients were categorized and equally distributed into healthy controls, newly diagnosed tuberculosis (TB), TB without hepatotoxicity and TB with hepatotoxicity groups based on their conventional liver function tests. Relative protein quantification was performed on depleted pooled serum samples of each representative group by LC-MS/MS, and validation of shortlisted protein was done by ELISA. Levels of all analysed biochemical parameters showed a statistical increment in the hepatotoxicity group compared to the other three groups, representing AT-DILI. Comparative proteomic analysis between TB with hepatotoxicity versus TB without hepatotoxicity groups highlighted 24 significant differentially expressed proteins, including PROS1, KNG1, CFH, LCAT, APCS and ADIPOQ. Identified proteins were involved in complement activation, triglyceride-rich lipoprotein particle remodelling and pathways comprising complement, coagulation cascades and cholesterol metabolism. Based on functional relevance, the serum amyloid P component (APCS) was shortlisted for validation, and it showed a similar trend as observed in the discovery phase with 100% sensitivity and 87% specificity; however, findings need exploration in larger cohorts.

A Quasi-experimental Evaluation of Performance Improvement Teams in the Safety-Net: A Labor-Management Partnership Model for Engaging Frontline Staff.

BACKGROUND: Unit-based teams (UBTs), initially developed by Kaiser Permanente and affiliated unions, are natural work groups of clinicians, managers, and frontline staff who work collaboratively to identify areas for improvement and implement solutions. OBJECTIVE: We evaluated the UBT model implemented by the Los Angeles County Department of Health Services in partnership with its union to engage frontline staff in improving patient care. DESIGN: We conducted a quasi-experimental study, comparing surveys at baseline and 6 months, among personnel in 10 clinics who received UBT training to personnel in 5 control clinics. We also interviewed staff from 5 clinics that received UBT training and 3 control clinics. PARTICIPANTS: We conducted 330 surveys and 38 individual, semi-structured interviews with staff at an outpatient facility in South Los Angeles. INTERVENTIONS: Each UBT leader received an 8-hour training in basic performance improvement methods, and each UBT was assigned a team "coach." MAIN MEASURES: Our outcome measure was 6-month change in the "adaptive reserve" score, the units' self-reported ability to make and sustain change. We analyzed transcripts of the interviews to find common themes regarding the UBT intervention. KEY RESULTS: The survey response rate was 63% (158/252) at baseline and 75% (172/231) at 6 months. There was a significant difference-in-change in adaptive reserve between UBTs and non-UBTs at 6 months (+0.11 vs -0.13; P = .02). Nine of the 10 UBTs reported increases in adaptive reserve and 8 UBTs reported decreased no-show rates or patient length of stay in clinic. Staff overwhelmingly felt the UBTs were a positive intervention because it allowed all levels of staff to have a voice in improvement. CONCLUSIONS: Our results indicate that partnership between management and unions to engage frontline staff in teams may be a useful tool to improve delivery of health care in a safety-net setting.