VA Palo Alto Healthcare System

About: VA Palo Alto Healthcare System is a healthcare organization based out in Palo Alto, California, United States. It is known for research contribution in the topics: Population & Health care. The organization has 2548 authors who have published 4605 publications receiving 209938 citations.

Simulation-based training in anesthesia crisis resource management (ACRM): a decade of experience

Abstract: Several gaps exist in the training of clinicians in health care domains, such as anesthesiology, that have the cognitive profile of complexity and dynamism. These features are shared with other industries such as commercial aviation. Training for cockpit crews on Crew Resource Management (CRM) emphasizes decision-making and teamwork principles. The authors created a simulation-based curriculum (ACRM) for anesthesiology based on principles of CRM in aviation. The training philosophy adapted to health care is one of training single-discipline crews to work in teams. The ACRM curriculum involves highly realistic simulation scenarios requiring complex decision making and interaction with multiple personnel. Scenarios are each followed by a detailed debriefing using videotapes of the simulation session. ACRM has been adopted at major health care institutions around the world. Special training for instructors is provided, especially concerning debriefing. The ACRM approach has been extended to a wide variety of other health care domains that involve complexity and dynamism, such as emergency and trauma medicine, intensive care, and cardiac arrest response teams. Simulation-based training based on CRM principles is expected to become routine in many health care settings in the coming decade.

Comparison of kindreds with parkinsonism and α‐synuclein genomic multiplications

Abstract: Genomic triplication of the alpha-synuclein gene recently has been associated with familial Parkinson's disease in the Spellman-Muenter kindred. Here, we present an independent family, of Swedish-American descent, with hereditary early-onset parkinsonism with dementia due to alpha-synuclein triplication. Brain tissue available from affected individuals in both kindreds provided the opportunity to compare their clinical, pathological, and biochemical phenotypes. Of note, studies of brain mRNA and soluble protein levels demonstrate a doubling of alpha-synuclein expression, consistent with molecular genetic data. Pathologically, cornu ammonis 2/3 hippocampal neuronal loss appears to be a defining feature of this form of inherited parkinsonism. The profound implications of alpha-synuclein overexpression for idiopathic synucleinopathies are discussed.

New mitochondrial DNA synthesis enables NLRP3 inflammasome activation

Abstract: Dysregulated NLRP3 inflammasome activity results in uncontrolled inflammation, which underlies many chronic diseases. Although mitochondrial damage is needed for the assembly and activation of the NLRP3 inflammasome, it is unclear how macrophages are able to respond to structurally diverse inflammasome-activating stimuli. Here we show that the synthesis of mitochondrial DNA (mtDNA), induced after the engagement of Toll-like receptors, is crucial for NLRP3 signalling. Toll-like receptors signal via the MyD88 and TRIF adaptors to trigger IRF1-dependent transcription of CMPK2, a rate-limiting enzyme that supplies deoxyribonucleotides for mtDNA synthesis. CMPK2-dependent mtDNA synthesis is necessary for the production of oxidized mtDNA fragments after exposure to NLRP3 activators. Cytosolic oxidized mtDNA associates with the NLRP3 inflammasome complex and is required for its activation. The dependence on CMPK2 catalytic activity provides opportunities for more effective control of NLRP3 inflammasome-associated diseases.

The pancreatic stellate cell: a star on the rise in pancreatic diseases.

Abstract: Pancreatic stellate cells (PaSCs) are myofibroblast-like cells found in the areas of the pancreas that have exocrine function. PaSCs are regulated by autocrine and paracrine stimuli and share many features with their hepatic counterparts, studies of which have helped further our understanding of PaSC biology. Activation of PaSCs induces them to proliferate, to migrate to sites of tissue damage, to contract and possibly phagocytose, and to synthesize ECM components to promote tissue repair. Sustained activation of PaSCs has an increasingly appreciated role in the fibrosis that is associated with chronic pancreatitis and with pancreatic cancer. Therefore, understanding the biology of PaSCs offers potential therapeutic targets for the treatment and prevention of these diseases.