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Introduction/purpose Most US adults (54%) do not meet the minimum exercise recommendations by the American College of Sports Medicine. Neuromuscular electrical stimulation (NMES) is a novel alternate strategy to induce muscle contraction. However, the effectiveness of NMES to improve insulin sensitivity and energy expenditure is unclear. The purpose of this study was to investigate the effects of 4 weeks of NMES on glucose tolerance in a sedentary overweight or obese population. Methods Participants (n = 10; age: 36.8 ± 3.8 years; BMI = 32 ± 1.3 kg/m2) were randomized into either control or NMES group. All participants received bilateral quadriceps stimulation (12 sessions; 30 min/session; three times/week at 50 Hz and 300 µs pulse width) altering pulse amplitude to either provide low-intensity sensory level (control; tingling sensation) or at high-intensity neuromuscular level (NMES; maximum tolerable levels with visible muscle contraction). Glucose tolerance was assessed by a 3-h oral glucose tolerance test (OGTT), and substrate utilization was measured by indirect calorimetry and body composition via dual X-ray absorptiometry at baseline and after 4 weeks of NMES intervention. Results Control and NMES groups had comparable fasting blood glucose, glucose tolerance, substrate utilization, and muscle mass at baseline. Four weeks of NMES resulted in a significant improvement in glucose tolerance measured by OGTT, whereas no change was observed in the control group. There was no change in substrate utilization and muscle mass in both control and NMES groups. Conclusion NMES is a novel and effective strategy to improve glucose tolerance in an at-risk overweight or obese sedentary population.

Background Multiple sclerosis (MS) is an inflammatory demyelinating disease that affects 2.5 million people worldwide. Growing evidence suggests that perturbation of the gut microbiota, the dense collection of microorganisms that colonize the gastrointestinal tract, plays a functional role in MS. Indeed, specific gut-resident bacteria are altered in patients with MS compared to healthy individuals, and colonization of gnotobiotic mice with MS-associated microbiota exacerbates preclinical models of MS. However, defining the molecular mechanisms by which gut commensals can remotely affect the neuroinflammatory process remains a critical gap in the field. Methods We utilized monophasic experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice and relapse-remitting EAE in SJL/J mice to test the effects of the products from a human gut-derived commensal strain of Lactobacillus paracasei (Lb). Results We report that Lb can ameliorate preclinical murine models of MS with both prophylactic and therapeutic administrations. Lb ameliorates disease through a Toll-like receptor 2-dependent mechanism via its microbe-associated molecular patterns that can be detected in the systemic circulation, are sufficient to downregulate chemokine production, and can reduce immune cell infiltration into the central nervous system (CNS). In addition, alterations in the gut microbiota mediated by Lb-associated molecular patterns are sufficient to provide partial protection against neuroinflammatory diseases. Conclusions Local Lb modulation of the gut microbiota and the shedding of Lb-associated molecular patterns into the circulation may be important physiological signals to prevent aberrant peripheral immune cell infiltration into the CNS and have relevance to the development of new therapeutic strategies for MS.

Viral encephalitis is a major cause of morbidity and mortality, but the manifestation of disease varies greatly between individuals even in response to the same virus. Microglia are professional antigen presenting cells that reside in the central nervous system (CNS) parenchyma that are poised to respond to viral insults. However, the role of microglia in initiating and coordinating the antiviral response is not completely understood. Utilizing Theiler’s murine encephalomyelitis virus (TMEV), a neurotropic picornavirus, and PLX5622, a small molecule inhibitor of colony-stimulating factor 1 receptor (CSF1R) signaling that can deplete microglia in the CNS; we investigated the role of the CSF1R-microglia axis in neurotropic picornavirus infection of C57BL/6J and SJL/J mice. These mouse strains differ in their ability to clear TMEV and exhibit different neurological disease in response to TMEV infection. CSF1R antagonism in C57BL/6J mice, which normally clear TMEV in the CNS, led to acute fatal encephalitis. In contrast, CSF1R antagonism in SJL/J mice, which normally develop a chronic CNS TMEV infection, did not result in acute encephalitis, but exacerbated TMEV-induced demyelination. Immunologically, inhibition of CSF1R in C57BL/6J mice reduced major histocompatibility complex II expression in microglia, decreased the proportion of regulatory T cells in the CNS, and upregulated proinflammatory pathways in CNS T cells. Acute CSF1R inhibition in SJL/J mice had no effect on microglial MHC-II expression and upregulated anti-inflammatory pathways in CNS T cells, however chronic CSF1R inhibition resulted in broad immunosuppression. Our results demonstrate strain-specific effects of the CSF1R-microglia axis in the context of neurotropic viral infection as well as inherent differences in microglial antigen presentation and subsequent T cell crosstalk that contribute to susceptibility to neurotropic picornavirus infection.

The central nervous system (CNS) is an important regulator of the gastrointestinal tract, and CNS dysfunction can result in significant and disabling gastrointestinal symptom manifestation. For patients with neuroimmunologic and neuroinflammatory conditions, the recognition of gastrointestinal symptoms is under-appreciated, yet the gastrointestinal manifestations have a dramatic impact on quality of life. The current treatment strategies, often employed independently by the neurologist and gastroenterologist, raise the question of whether such patients are being treated optimally when siloed in one specialty. Neuroimmunogastroenterology lies at the borderlands of medical specialties, and there are few resources to guide neurologists in this area. Here, we provide an overview highlighting the potential mechanisms of crosstalk between immune-mediated neurological disorders and gastrointestinal dysfunction.

Background The need for high-quality evidence that is applicable in real-world, routine settings continues to increase. Pragmatic trials are designed to evaluate the effectiveness of interventions in real-world settings, whereas explanatory trials aim to test whether an intervention works under optimal situations. There is a continuum between explanatory and pragmatic trials. Most trials have aspects of both, making it challenging to label and categorize a trial and to evaluate its potential for translation into practice. Methods We summarize our experience applying the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) combined with external validity items based on the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to three studies to provide a more robust and comprehensive assessment of trial characteristics related to translation of research. We summarize lessons learned using domains from the combined frameworks for use in study planning, evaluating specific studies, and reviewing the literature and make recommendations for future use. Results A variety of coders can be trained to use the PRECIS and RE-AIM domains. These domains can also be used for diverse purposes, content areas, and study types, but are not without challenges. Both PRECIS and RE-AIM domains required modification in two of the three studies to evaluate and rate domains specific to study type. Lessons learned involved: dedicating enough time for training activities related to the domains; use of reviewers with a range of familiarity with specific study protocols; how to best adapt ratings that reflect complex study designs; and differences of opinion regarding the value of creating a composite score for these criteria. Conclusions Combining both frameworks can specifically help identify where and how a study is and is not pragmatic. Using both PRECIS and RE-AIM allows for standard reporting of key study characteristics related to pragmatism and translation. Such measures should be used more consistently to help plan more pragmatic studies, evaluate progress, increase transparency of reporting, and integrate literature to facilitate translation of research into practice and policy. Electronic supplementary material The online version of this article (doi:10.1186/s13012-014-0096-x) contains supplementary material, which is available to authorized users.

The work of the CDC, National Institutes of Health (NIH), and other HHS agencies on communicable diseases in the developing world is well known. However, today, noncommunicable disease accounts for more than 60% of deaths around the world, of which 80% are in the developing world [1]. The epidemic of noncommunicable disease is growing and shifting from high-income countries to low- and middle-income countries (LMICs), where little research has been done, and minimal research capacity currently exists. Another challenge is the development of a “rapid learning science” grounded in methodology that is rigorous while also being responsive to short-term needs of communities, health systems, and policy makers [2]. There is a need to apply the lessons learned from HIV/AIDS, which ultimately converted erroneous myths that HIV was too complex, costly, and prevalent to prevent in the developing world into effective strategies to reduce costs, increase access to health services, and strengthen health systems [3]. This lesson from HIV/AIDS suggests that research conducted in LMICs could provide significant and innovative advancements in understanding, preventing, and treating chronic diseases for both developing and developed countries. Such research would likely include “disruptive innovations” as proposed by Paul Farmer [4], Clayton Christensen [5], and Santosh Krishna [6], providing needed services in innovative ways that bring a much more affordable product or service that is simple to integrate into a health service market. New international collaborations dedicated to an implementation and evaluation research agenda in chronic diseases are needed, and the behavioral and social sciences will be critical to advance research in global health. NIH, and particularly the NIH Fogarty International Center (FIC), has long supported international collaborations for research, training, health communications, and other activities related to preventing and controlling disease. One of the goals in the new FIC strategic plan is to expand training in and application of implementation science [7]. NIH, and specifically the FIC and the National Heart Lung and Blood Institute, are members of the Global Alliance for Chronic Diseases [8]. This alliance has global reach and brings together six major national health research councils. A major focus of the alliance is on chronic diseases in LMIC and among low-income and indigenous populations in developed countries. The goal is to support research on low-cost interventions and to build capacity in research, training, and healthcare delivery. Another example of NIH involvement in global health is the National Cancer Institute’s (NCI) co-funding of the International Tobacco and Health Research and Capacity Building Program. This program supports transdisciplinary research and capacity-building projects that address the burden of tobacco consumption in LMICs and promotes international cooperation between scientists and institutions in LMICs and investigators in high-income nations. The International Tobacco Control Policy Evaluation Project (ITC Project), funded by NCI, will evaluate and improve the understanding of the effect of the tobacco control policies implemented as part of the Framework Convention on Tobacco Control (FCTC). The ITC Project includes more than 20 countries, including many LMICs. It is the only international study that is specifically evaluating the effectiveness of the FCTC policies, such as implementing clean indoor air policies and graphic health warnings on cigarette packages. Disease-screening initiatives, such as the International Cancer Screening Network (ICSN) sponsored by NCI, are dedicated to collaborative research aimed at identifying and fostering efficient and effective approaches to disease control worldwide through population-based screening. ICSN is a voluntary consortium of 28 countries that meets biennially and has active population-based screening programs. The 4th Annual NIH Conference on the Science of Dissemination and Implementation: Policy and Practice, held on March 21–22, 2011, provided a forum for communicating and networking with international experts about the science of dissemination and implementation. One of the goals of this year’s conference was to facilitate international partnerships and expand the research base focused on global health issues. In parallel with the conference, NIH offered a workshop on impact evaluation, focused on how to incorporate rigorous impact evaluation methodologies into operations and implementation research, particularly when operating in a LMIC context. Past research suggests that international collaborations can inform efforts to identify solutions to the US health challenges in two major ways. First, the evaluation of major differences in health policy, context, and the effect of health policies on health and behavioral outcomes can inform future policies in the USA as well as LMICs. Second, study of health policy factors and outcomes within a given country likely underestimates the effect of policies because of the restricted range of policies within any given country. International comparisons can provide a better sense of multi-level effects within various contexts. The programs and activities summarized above are promising beginnings, but there are many remaining opportunities for behavioral and social sciences to address global health needs. The examples in this column are illustrative but not inclusive of all NIH global health initiatives. Global health is one of NIH Director Francis Collins’s five primary areas of focus [9], so new and continued opportunities for global health research are likely.

Background The National Cancer Institute (NCI) has supported implementation science for over a decade. We explore the application of implementation science across the cancer control continuum, including prevention, screening, treatment, and survivorship. Methods We reviewed funding trends of implementation science grants funded by the NCI between 2000 and 2012. We assessed study characteristics including cancer topic, position on the T2–T4 translational continuum, intended use of frameworks, study design, settings, methods, and replication and cost considerations. Results We identified 67 NCI grant awards having an implementation science focus. R01 was the most common mechanism, and the total number of all awards increased from four in 2003 to 15 in 2012. Prevention grants were most frequent (49.3%) and cancer treatment least common (4.5%). Diffusion of Innovations and Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) were the most widely reported frameworks, but it is unclear how implementation science models informed planned study measures. Most grants (69%) included mixed methods, and half reported replication and cost considerations (49.3%). Conclusions Implementation science in cancer research is active and diverse but could be enhanced by greater focus on measures development, assessment of how conceptual frameworks and their constructs lead to improved dissemination and implementation outcomes, and harmonization of measures that are valid, reliable, and practical across multiple settings.