Sleep and circadian rhythms are increasingly recognized as important determinants of health and functioning. Poor sleep health and misaligned circadian rhythms increase the risk of adverse health outcomes such as depression, cognitive impairment, cardiovascular disease, diabetes, and even mortality. However, we know very little about how sleep and circadian disruption lead to health risks later in life.
Cell signaling actions mediated by reduction-oxidation (redox)-dependent post-translational modifications include the oxidation, glutathionylation, S-nitrosation, and alkylation of cysteine. These reactions intimately link metabolic and inflammatory status with changes in cell and organ function, since many enzymes, receptors and transcriptional regulatory proteins mediating metabolic and inflammatory responses contain functionally- significant hyperactive cysteine thiols.
Trauma is the leading cause of death in young people worldwide and has an estimated annual healthcare cost of 400 billion dollars per year in the United States alone. Survivors of trauma suffer from severe morbidity in the form of organ failure and thromboembolic complications, which are driven, in large part, by excessive inflammation and a vicious cascade of coagulation abnormalities.
Training in lesion-symptom mapping for speech-language research Abstract: Researchers rely upon the lesion method to evaluate the speech-language status of stroke survivors and draw inferences about underlying brain function. This use of neuropsychology is highly valued in basic speech- language research because it can support causal inferences about brain structure/function relationships. Crucially, advances in analytic techniques and brain image computing are creating a new landscape for neuropsychological research.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder, afflicting approximately 1 in 5,000 people, that is characterized by development of arteriovenous malformations (AVMs). These fragile, direct connections between arteries and veins can lead to hemorrhage, anemia, brain abscess, or stroke. For lung, brain, and nasal lesions, the primary treatment options are invasive procedures that ablate, resect, or block flow through the AVM.
More than 2 million Americans are hospitalized with sepsis each year, and account for 1 out of every 2 to 3 hospital deaths. Most efforts to reduce mortality among septic patients begin with the premise that patients are largely similar, and that ether moving treatment earlier or targeting therapeutics to a single mechanism will improve outcomes. Drawing insights from rheumatology and oncology, as well as my sepsis biomarker work during my K23 mentored career development award, we argue that endotypes (biologic subtypes) play an important role in the pathogenesis and outcome of sepsis.
African Americans and Latino/Hispanic Americans have a higher risk of death from heart disease and stroke than any other ethnic group in the US. These same ethnic groups are also at risk for many severe inherited blood disorders such as sickle cell disease and thalassemia, which are prevalent only in minority populations. Moreover, they are more likely than other ethnic groups to suffer common respiratory diseases such as asthma. Many of these diseases impact the heart, lung, and blood, which are the focus of cutting-edge research at the University of Pittsburgh.
This application is for a Mentored Patient-Oriented Research Career Development Award entitled “Metabolic Effects of Early Nutritional Support in Sepsis: A Translational Investigation.” I am a pulmonary and critical care physician at the University of Pittsburgh Medical Center who requires additional training to develop expertise as a translational researcher using metabolic assessment studies in animal models of sepsis to guide the development of interventions in patients with critical illness.
Heart Failure (HF) is a disease of epidemic proportion in the US affecting over 5 million individuals. Cardiac resynchronization therapy (CRT) is an established therapy for many patients with advanced HF. CRT can be delivered through a pacemaker (CRT-P) or a defibrillator (CRT-D). CRT-P devices are smaller and cost a fraction of the price of CRT-D devices. Compared to optimal pharmacological treatment, both CRT-P and CRT- D are proven to reduce mortality and improve quality of life (QOL).
It has long been recognized that dysregulated inflammation causes many human diseases. The systemic inflammatory response, best associated with infections (termed sepsis), is a common and life- threatening example of hyperinflammatory damage. Very little is known about what regulates an appropriate versus excessive inflammatory response, or how to manipulate inflammation to prevent damage. The goal of this proposal is to understand how mutations in a protein called NLRC4 result in a human sepsis-like phenotype known as Macrophage Activation Syndrome (MAS).
