PPRX-1701, a nanoparticle formulation of 6'-bromoindirubin acetoxime, improves delivery and shows efficacy in preclinical GBM models.

Derivatives of the Chinese traditional medicine indirubin have shown potential for the treatment of cancer through a range of mechanisms. This study investigates the impact of 6'-bromoindirubin-3'-acetoxime (BiA) on immunosuppressive mechanisms in glioblastoma (GBM) and evaluates the efficacy of a BiA nanoparticle formulation, PPRX-1701, in immunocompetent mouse GBM models. Transcriptomic studies reveal that BiA downregulates immune-related genes, including indoleamine 2,3-dioxygenase 1 (IDO1), a critical enzyme in the tryptophan-kynurenine-aryl hydrocarbon receptor (Trp-Kyn-AhR) immunosuppressive pathway in tumor cells.

The Cost of ARDS: A Systematic Review.

Background: ARDS is an inflammatory condition of the lungs and is a common condition in adult ICUs. The resources required and costs of care for patients with ARDS are significant because of the severity of the illness and extended ICU lengths of stay.

Research Question: What are the costs associated with ARDS?

Study Design And Methods: We systematically searched the literature through April 29, 2021, for articles relevant to ARDS and costs.

Adenoviral vector vaccine platforms in the SARS-CoV-2 pandemic.

Adenoviral vectors have been explored as vaccine agents for a range of infectious diseases, and their ability to induce a potent and balanced immune response made them logical candidates to apply to the COVID-19 pandemic. The unique molecular characteristics of these vectors enabled the rapid development of vaccines with advanced designs capable of overcoming the biological challenges faced by early adenoviral vector systems. These successes and the urgency of the COVID-19 situation have resulted in a flurry of candidate adenoviral vector vaccines for COVID-19 from both academia and industry.

Vector Strategies to Actualize B Cell-Based Gene Therapies.

Recent developments in genome editing and delivery systems have opened new possibilities for B cell gene therapy. CRISPR-Cas9 nucleases have been used to introduce transgenes into B cell genomes for subsequent secretion of exogenous therapeutic proteins from plasma cells and to program novel B cell Ag receptor specificities, allowing for the generation of desirable Ab responses that cannot normally be elicited in animal models. Genome modification of B cells or their progenitor, hematopoietic stem cells, could potentially substitute Ab or protein replacement therapies that require multiple injections over the long term.

Adenoviral vectors for in vivo delivery of CRISPR-Cas gene editors.

Harnessing the bacterial clustered regularly interspaced short palindromic repeats (CRISPR) system for genome editing in eukaryotes has revolutionized basic biomedical research and translational sciences. The ability to create targeted alterations of the genome through this easy to design system has presented unprecedented opportunities to treat inherited disorders and other diseases such as cancer through gene therapy. A major hurdle is the lack of an efficient and safe in vivo delivery system, limiting most of the current gene therapy efforts to ex vivo editing of extracted cells.

Perspectives on strained intensive care unit capacity: A survey of critical care professionals.

Background: Strained intensive care unit (ICU) capacity represents a supply-demand mismatch in ICU care. Limited data have explored health care worker (HCW) perceptions of strain.

Methods: Cross-sectional survey of HCW across 16 Alberta ICUs.

Healthcare Provider Perceptions of Causes and Consequences of ICU Capacity Strain in a Large Publicly Funded Integrated Health Region: A Qualitative Study.

Objectives: Discrepancy in the supply-demand relationship for critical care services precipitates a strain on ICU capacity. Strain can lead to suboptimal quality of care and burnout among providers and contribute to inefficient health resource utilization. We engaged interprofessional healthcare providers to explore their perceptions of the sources, impact, and strategies to manage capacity strain.

Focused Critical Care Echocardiography: Development and Evaluation of an Image Acquisition Assessment Tool.

Objectives: Little attention has been placed on assessment tools to evaluate image acquisition quality for focused critical care echocardiography. We designed a novel assessment tool to objectively evaluate the image acquisition skills of critical care trainees learning focused critical care echocardiography and examined the tool for evidence of validity.

Design: Prospective observational study.

Coma, metabolic acidosis, and methemoglobinemia in a patient with acetaminophen toxicity.

We present a case of early coma, metabolic acidosis and methemoglobinemia after substantial acetaminophen toxicity in the absence of hepatic failure. A 77-year-old female presented to the emergency department with a decreased level of consciousness. She was found unresponsive by a family member in her bed, and was reported to be acting normally when she was last seen eight hours earlier.

In vitro and in vivo enhancement of ganciclovir-mediated bystander cytotoxicity with gemcitabine.

To improve bystander cell killing with HSV-TK/GCV, we have utilized dFdCyd to reduce endogenous dGTP, which competes with GCVTP for incorporation into DNA. In this study we demonstrate the ability of dFdCyd to enhance GCV-mediated bystander cytotoxicity in cultured SW620 human colon carcinoma cells as well as in a murine xenograft model. In vitro, dFdCyd reduced cellular dGTP levels and produced a fourfold increase in the GCVTP:dGTP ratio.

Intravenous immunoglobulin for severe infections: a survey of Canadian specialists.

Purpose: To survey the opinions of Canadian critical care medicine and infectious disease specialists about the use of intravenous immunoglobulin (IVIG) for the treatment of severe infections.

Materials And Methods: A scenario-based, cross-sectional survey of Canadian critical care medicine and infectious disease specialists was conducted from March to June 2003.

Results: The response rate was 291/487 (60%).

Neoplastic reversal of human ovarian carcinoma cells transfected with connexin43.

Gap junctional intercellular communication and expression of gap junction proteins (connexins) are decreased frequently in neoplastic cells including human ovarian carcinoma cells. In order to test the hypothesis that these changes contribute to the neoplastic phenotype of ovarian carcinoma cells, we transfected human ovarian carcinoma SKOV-3 cells with connexin43. Stable, connexin43-expressing transfectants were characterized for cell proliferation in vitro in normal, low-serum, and serum-free culture medium, for tumorigenicity in nude mice, and for sensitivity to adriamycin in vitro.

Multi-log cytotoxicity of carbocyclic 2'-deoxyguanosine in HSV-TK-expressing human tumor cells.

Ganciclovir (GCV) is widely used as a prodrug for selective activation in tumor cells expressing herpes simplex virus thymidine kinase (HSV-TK) because of its ability to induce multi-log cytotoxicity to HSV-TK-expressing as well as nonexpressing bystander cells. We now report that another substrate for HSV-TK, D-carbocyclic 2'-deoxyguanosine (CdG), induces multi-log cytotoxicity in HSV-TK-expressing and bystander cells at concentrations View Article and Find Full Text PDF