From Inputs to Impacts: Assessing and Communicating the Full Value of Biomedical Research.

Assessing and communicating the full value of biomedical research is essential to answer calls from the government and the public demanding accountability for the spending of public funds. In academic settings, however, research success is measured largely in terms of grant funding received or the number of peer-reviewed publications produced. These credible and time-tested metrics miss the full picture of the scientific process, which continues to confer benefits to patients, communities, and the health care system well after an article is published.

The U.S. Public's Investment in Medical Research: An Evolving Social Contract.

Medical researchers and their institutions are operating under extraordinary financial stress. More than a decade after completion of the 5-year doubling of the National Institutes of Health budget, the medical research community must confront a significant loss in National Institutes of Health purchasing power and downward pressures in federal discretionary spending. In part, this trend results from a federal budget stalemate over the growth in entitlement programs, particularly spending on medical care.

MD-PhD training: looking back and looking forward.

MD-PhD programs provide rigorous, integrated training for physician-scientists, enabling them to frame scientific questions in unique ways and to apply clinical insight to fundamental science. Few would question the influential contributions of MD-PhD physician-scientists in advancing medical science. In this issue of Academic Medicine, Jeffe et al affirm high levels of excellence in educational outcomes from MD-PhD training programs at U.

Training the translational research teams of the future: UC Davis-HHMI Integrating Medicine into Basic Science program.

There is a need for successful models of how to recruit, train, and retain bench scientists at the earliest stages of their careers into translational research. One recent, promising model is the University of California Davis Howard Hughes Medical Institute Integrating Medicine into Basic Science (HHMI-IMBS) program, part of the HHMI Med into Grad initiative. This paper outlines the HHMI-IMBS program's logic, design, and curriculum that guide the goal of research that moves from bedside to bench.

Making equity a value in value-based health care.

Equity in health and health care in America continues to be a goal unmet. Certain demographic groups in the United States-including racial and ethnic minorities and individuals with lower socioeconomic status-have poorer health outcomes across a wide array of diseases, and have higher all-cause mortality. Yet despite growing understanding of how social-, structural-, and individual-level factors maintain and create inequities, solutions to reduce or eliminate them have been elusive.

The implications of comparative effectiveness research for academic medicine.

With growing constraints on government spending, policy makers are investing in comparative effectiveness research (CER) to attempt to bring the power of science to bear on the problems of suboptimal outcomes and high cost in the U.S. health care system.

Distinct tachykinin NK(1) receptor function in primate nucleus tractus solitarius neurons is dysregulated after second-hand tobacco smoke exposure.

Background And Purpose: Second-hand tobacco smoke (SHS) exposure in children increases the risk of asthma and sudden infant death syndrome. Epidemiological and experimental data have suggested SHS can alter neuroplasticity in the CNS, associated with substance P. We hypothesized that exposure to SHS in young primates changed the effect of substance P on the plasticity of neurons in the nucleus tractus solitarius (NTS), where airway sensory information is first processed in the CNS.

Moving comparative effectiveness research into practice: implementation science and the role of academic medicine.

The success of the federal investment in comparative effectiveness research will hinge on using the power of science to guide reforms in health care delivery and improve patient-centered outcomes. Translating the results of comparative effectiveness research into practice calls for the rigors of implementation science to ensure the efficient and systematic uptake, dissemination, and endurance of these innovations. Academic medicine can help answer the call by thoroughly integrating its research and training missions with clinical care that is focused on patient-centered outcomes; building multidisciplinary teams that include a wide range of experts such as clinicians, clinical and implementation scientists, systems engineers, behavioral economists, and social scientists; and training future care providers, scientists, and educators to carry innovations forward.

Commentary: Putting evidence to work: an expanded research agenda for academic medicine in the era of health care reform.

The historic Patient Protection and Affordable Care Act (HR 3590) signed into law by President Obama has brought into sharp focus the need and opportunity for an expanded continuum of biomedical research. An updated research agenda must build on basic science and classical clinical investigation to place a more deliberate emphasis on patient- and population-outcome-oriented science and to apply science to help transform our current inefficient and expensive health care system into a more evidence-based system of effective, coordinated, safe, and patient-centered health care. If academic medicine is to play a leading role in this 21st-century transformation of health care through research, as it did in the 20th century, those in the community must think strategically about what needs to be done to be part of the solution for transforming the nation's health care delivery systems and prevention strategies, and the changes in institutional, organizational, and individual behaviors and values required to get there.

House-dust mite allergen and ozone exposure decreases histamine H3 receptors in the brainstem respiratory nuclei.

Allergic airway diseases in children are a common and a growing health problem. Changes in the central nervous system (CNS) have been implicated in contributing to some of the symptoms. We hypothesized that airway allergic diseases are associated with altered histamine H3 receptor expression in the nucleus tractus solitarius (NTS) and caudal spinal trigeminal nucleus, where lung/airway and nasal sensory afferents terminate, respectively.

Retrograde release of endocannabinoids inhibits presynaptic GABA release to second-order baroreceptive neurons in NTS.

In prior studies, we found that activation of cannabinoid-1 receptors in the nucleus tractus solitarii (NTS) prolonged baroreflex-induced sympathoinhibition in rats. In many regions of the central nervous system, activation of cannabinoid-1 receptors presynaptically inhibits γ-aminobutyric acid (GABA) release, disinhibiting postsynaptic neurons. To determine if cannabinoid-1 receptor-mediated presynaptic inhibition of GABA release occurs in the NTS, we recorded miniature inhibitory postsynaptic currents in anatomically identified second-order baroreceptive NTS neurons in the presence of ionotropic glutamate receptor antagonists and tetrodotoxin.

Postexercise hypotension: central mechanisms.

A single bout of exercise can lead to a postexercise decrease in blood pressure in hypertensive individuals, called postexercise hypotension. Compelling evidence suggests that the central baroreflex pathway plays a crucial role in the development of postexercise hypotension. This review focuses on the exercise-induced changes in brainstem nuclei involved in blood pressure regulation.

Issues and challenges of non-tenure-track research faculty: the UC Davis School of Medicine experience.

Nationally, medical schools are appointing growing numbers of research faculty into non-tenure-track positions, paralleling a similar trend in universities. The American Association of University Professors (AAUP) issued a statement expressing concern that the marked growth in non-tenure-track faculty can undermine educational quality, academic freedom, and collegiality. Like other medical schools, the UC Davis School of Medicine has had a rise in non-tenure-track faculty in order to enhance its research mission, in particular in the Salaried Adjunct faculty track (SalAdj).

Secondhand smoke exposure alters K+ channel function and intrinsic cell excitability in a subset of second-order airway neurons in the nucleus tractus solitarius of young guinea pigs.

Extended exposure to secondhand smoke (SHS) in infants and young children increases the incidence of cough, wheeze, airway hyper-reactivity and the prevalence and earlier onset of asthma. The adverse effects may result from environmentally-induced plasticity in the neural network regulating cough and airway function. Using whole-cell patch-clamp recordings in brainstem slices containing anatomically identified second-order lung afferent neurons in the nucleus tractus solitarius (NTS), we determined the effects of extended SHS exposure in young guinea pigs for a duration equivalent to human childhood on the intrinsic excitability of NTS neurons.

Secondhand tobacco smoke exposure differentially alters nucleus tractus solitarius neurons at two different ages in developing non-human primates.

Exposing children to secondhand tobacco smoke (SHS) is associated with increased risk for asthma, bronchiolitis and SIDS. The role for changes in the developing CNS contributing to these problems has not been fully explored. We used rhesus macaques to test the hypothesis that SHS exposure during development triggers neuroplastic changes in the nucleus tractus solitarius (NTS), where lung sensory information related to changes in airway and lung function is first integrated.

A novel postsynaptic group II metabotropic glutamate receptor role in modulating baroreceptor signal transmission.

The nucleus tractus solitarius (NTS) is essential for orchestrating baroreflex control of blood pressure. When a change in blood pressure occurs, the information is transmitted by baroreceptor afferent fibers to the central network by glutamate binding to ionotropic glutamate receptors on second-order baroreceptor neurons. Glutamate also activates presynaptic group II and III metabotropic glutamate receptors (mGluRs), depressing both glutamate and GABA release to modulate baroreceptor signal transmission.

Central neuroplasticity and decreased heart rate variability after particulate matter exposure in mice.

Background: Epidemiologic studies show that exposure to fine particulate matter [aerodynamic diameter < or = 2.5 microm (PM(2.5))] increases the total daily cardiovascular mortality.

Generational forecasting in academic medicine: a unique method of planning for success in the next two decades.

Multigenerational teams are essential to the missions of academic health centers (AHCs). Generational forecasting using Strauss and Howe's predictive model, "the generational diagonal," can be useful for anticipating and addressing issues so that each generation is effective. Forecasts are based on the observation that cyclical historical events are experienced by all generations, but the response of each generation differs according to its phase of life and previous defining experiences.

Exercise reduces GABA synaptic input onto nucleus tractus solitarii baroreceptor second-order neurons via NK1 receptor internalization in spontaneously hypertensive rats.

A single bout of mild to moderate exercise can lead to a postexercise decrease in blood pressure in hypertensive subjects, namely postexercise hypotension (PEH). The full expression of PEH requires a functioning baroreflex, hypertension, and activation of muscle afferents (exercise), suggesting that interactions in the neural networks regulating exercise and blood pressure result in this fall in blood pressure. The nucleus tractus solitarii (NTS) is the first brain site that receives inputs from nerves carrying blood pressure and muscle activity information, making it an ideal site for integrating cardiovascular responses to exercise.

Extended secondhand tobacco smoke exposure induces plasticity in nucleus tractus solitarius second-order lung afferent neurons in young guinea pigs.

Infants and young children experiencing extended exposure to secondhand smoke (SHS) have an increased occurrence of asthma, as well as increased cough, wheeze, mucus production and airway hyper-reactivity. Plasticity in lung reflex pathways has been implicated in causing these symptoms, as have changes in substance P-related mechanisms. Using whole-cell voltage-clamp recordings and immunohistochemistry in brainstem slices containing anatomically identified second-order lung afferent nucleus tractus solitarius (NTS) neurons, we determined whether extended SHS exposure during the equivalent period of human childhood modified evoked or spontaneous excitatory synaptic transmission, and whether those modifications were altered by endogenous substance P.

Short-term secondhand smoke exposure decreases heart rate variability and increases arrhythmia susceptibility in mice.

Exposure to secondhand smoke (SHS), a major indoor air pollutant, is linked to increased cardiovascular morbidity and mortality, including cardiac arrhythmias. However, the mechanisms underlying the epidemiological findings are not well understood. Impaired cardiac autonomic function, indexed by reduced heart rate variability (HRV), may represent an underlying cause.

Air pollutants and cough.

Epidemiological studies have shown that exposure to air pollution is associated with respiratory symptoms and decreases in lung function. This paper reviews recent literature showing that exposure to particulate matter, irritant gases, environmental tobacco smoke (ETS), mixed pollutants, and molds is associated with an increase in cough and wheeze. Some pollutants, like particulate matter and mixed pollutants, appear to increase cough at least as much as wheeze.

Plasticity of brainstem mechanisms of cough.

The cough reflex is a brainstem reflex, consisting of specific sensory afferent nerves which trigger the reflex, by transmitting the sensory input over vagal or laryngeal nerves to a brainstem circuitry which processes and ultimately transforms the sensory input into a complex motor output to generate cough. The first synaptic target for the primary cough-related sensory input is the second-order neurons in the nucleus tractus solitarius (NTS). This position in the reflex pathway and intricate local circuits within the nucleus make it a strategic site where the sensory information can be modified.

Plasticity in the nucleus tractus solitarius and its influence on lung and airway reflexes.

The nucleus tractus solitarius (NTS) is the first central nervous system (CNS) site for synaptic contact of the primary afferent fibers from the lungs and airways. The signal processing at these synapses will determine the output of the sensory information from the lungs and airways to all downstream synapses in the reflex pathways. The second-order NTS neurons bring to bear their own intrinsic and synaptic properties to temporally and spatially integrate the sensory information with inputs from local networks, higher brain regions, and circulating mediators, to orchestrate a coherent reflex output.