The NJ Alliance for Clinical and Translational Science (NJ ACTS) experience: Responding at "warp speed" to COVID-19.

Introduction: The COVID-19 pandemic's need for life-saving treatments and a "warp speed" vaccine challenged the National Institutes of Health's Clinical and Translational Science Award (CTSA) recipients to improve their methods and processes in conducting clinical research. While CTSA recipient, New Jersey Alliance for Clinical and Translational Science (NJ ACTS), responded to this call to action with significant clinical research milestones, a comprehensive understanding of regulatory metrics during the COVID-19 pandemic is uncertain. The objective of this research is to identify, compare, and contrast metrics that illustrate the effectiveness of NJ ACTS's research mobilization efforts during COVID-19.

Heme oxygenase-1-dependent central cardiorespiratory adaptations to chronic intermittent hypoxia in mice.

Chronic intermittent hypoxia (CIH) increases sympathetic tone and respiratory instability. Our previous work showed that chronic hypoxia induces the oxygen-sensing enzyme heme oxygenase-1 (HO-1) within the C1 sympathoexcitatory region and the pre-Bötzinger complex (pre-BötC). We therefore examined the effect of CIH on time course of induced expression of HO-1 within these regions and determined whether the induction of HO-1 correlated with changes in respiratory, sigh frequency, and sympathetic responses (spectral analysis of heart rate) to acute hypoxia (10% O) during 10 days of exposure to CIH in chronically instrumented awake wild-type (WT) and HO-1 null mice (HO-1).

Heme oxygenase-1 and chronic hypoxia.

A myriad of changes are necessary to adapt to chronic hypoxemia. Key among these changes increases in arterial oxygen carrying capacity, ventilation and sympathetic activity. This requires the induction of several gene products many of which are regulated by the activity of HIF-1α, including HO-1.

Opioids protect against substantia nigra cell degeneration under conditions of iron deprivation: a mechanism of possible relevance to the Restless Legs Syndrome (RLS) and Parkinson's disease.

Hypofunction of the endogenous opioid, dopamine and iron systems are implicated in the pathogenesis of Restless Legs Syndrome (RLS). Therefore, we probed the interrelationship of these 3 systems in an in vitro model. Cell cultures of the substantia nigra (SN) of Sprague-Dawley rats were established and the cells were determined to be primarily dopaminergic.

Heme oxygenase-1-dependent central cardiorespiratory adaptations to chronic hypoxia in mice.

Adaptations to chronic hypoxia (CH) could reflect cellular changes within the cardiorespiratory regions of the rostral ventrolateral medulla (RVLM), the C1 region, and the pre-Bötzinger complex (pre-BötC). Previous studies have shown that the hypoxic chemosensitivity of these regions are heme oxygenase (HO) dependent and that CH induces HO-1. To determine the time course of HO-1 induction within these regions and explore its relevance to the respiratory and sympathetic responses during CH, the expression of HO-1 mRNA and protein in the RVLM and measures of respiration, sigh frequency, and sympathetic activity (spectral analysis of heart rate) were examined during 10 days of CH.

Medical student research exposure via a series of modular research programs.

Background: The falling percentage of doctors of medicine applying for National Institute of Health-funded research grants is 1 indicator that physician-scientists are a disappearing breed. This is occurring at a time when increased translational, disease-oriented, patient-oriented, and clinical research are national goals. One of the keys to providing sufficient numbers of physician-scientists to support this goal is the active targeting of medical students.

Heme oxygenase is necessary for the excitatory response of cultured neonatal rat rostral ventrolateral medulla neurons to hypoxia.

Heme oxygenase has been linked to the oxygen-sensing function of the carotid body, pulmonary vasculature, cerebral vasculature, and airway smooth muscle. We have shown previously that the cardiorespiratory regions of the rostral ventrolateral medulla are excited by local hypoxia and that heme oxygenase-2 (HO-2) is expressed in the hypoxia-chemosensitive regions of the rostral ventrolateral medulla (RVLM), the respiratory pre-Bötzinger complex, and C1 sympathoexcitatory region. To determine whether heme oxygenase is necessary for the hypoxic-excitation of dissociated RVLM neurons (P1) cultured on confluent medullary astrocytes (P5), we examined their electrophysiological responses to hypoxia (NaCN and low Po(2)) using the whole-cell perforated patch clamp technique before and after blocking heme oxygenase with tin protoporphyrin-IX (SnPP-IX).

Oxygen-sensing neurons in the central nervous system.

This mini-review summarizes the present knowledge regarding central oxygen-chemosensitive sites with special emphasis on their function in regulating changes in cardiovascular and respiratory responses. These oxygen-chemosensitive sites are distributed throughout the brain stem from the thalamus to the medulla and may form an oxygen-chemosensitive network. The ultimate effect on respiratory or sympathetic activity presumably depends on the specific neural projections from each of these brain stem oxygen-sensitive regions as well as on the developmental age of the animal.