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BACKGROUND: Evidence-based practices (EBPs) are frequently adapted in response to the dynamic contexts in which they are implemented. Adaptation is defined as the degree to which an EBP is altered to fit the setting or to improve fit to local context and can be planned or unplanned. Although adaptations are common and necessary to maximizing the marginal impact of EBPs, little attention has been given to the economic consequences and how adaptations affect marginal costs. DISCUSSION: In assessing the economic consequences of adaptation, one should consider its impact on core components, the planned adaptive periphery, and the unplanned adaptive periphery. Guided by implementation science frameworks, we examine how various economic evaluation approaches accommodate the influence of adaptations and discuss the pros and cons of these approaches. Using the Framework for Reporting Adaptations and Modifications to Evidence-based interventions (FRAME), mixed methods can elucidate the economic reasons driving the adaptations. Micro-costing approaches are applied in research that integrates the adaptation of EBPs at the planning stage using innovative, adaptive study designs. In contrast, evaluation of unplanned adaptation is subject to confounding and requires sensitivity analysis to address unobservable measures and other uncertainties. A case study is presented using the RE-AIM framework to illustrate the costing of adaptations. In addition to empirical approaches to evaluating adaptation, simulation modeling approaches can be used to overcome limited follow-up in implementation studies. CONCLUSIONS: As implementation science evolves to improve our understanding of the mechanisms and implications of adaptations, it is increasingly important to understand the economic implications of such adaptations, in addition to their impact on clinical effectiveness. Therefore, explicit consideration is warranted of how costs can be evaluated as outcomes of adaptations to the delivery of EBPs.

Pyrethroid and neonicotinoid pesticides control an array of insect pests in leafy greens, but there are concerns about the off-site movement and potential water quality impacts of these chemicals. Effective on-farm management practices can eliminate aquatic toxicity and pesticides in runoff. This project evaluated an integrated vegetated treatment system (VTS), including the use of polyacrylamide (PAM), for minimizing the toxicity of imidacloprid and permethrin pesticides in runoff. The VTS incorporated a sediment trap to remove coarse particles, a grass-lined ditch with compost swales to remove suspended sediment and insecticides, and granulated activated carbon (GAC) or biochar to remove residual insecticides. Runoff was sampled throughout the VTS and analyzed for pesticide concentrations, and aquatic toxicity using the midge Chironomusdilutus and the amphipod Hyalella azteca. In simulated runoff experiments, the VTS reduced suspended sediment load by 88%, and imidacloprid and permethrin load by 97% and 99%, respectively. In runoff events from a conventionally grown lettuce field, suspended sediment load was reduced by 98%, and insecticide load by 99%. Toxicity was significantly reduced in approximately half of the simulated runoff events, and most of the lettuce runoff events. Integrated vegetated treatment systems that include components for treating soluble and hydrophobic pesticides are vital tools for reducing pesticide load and occurrence of pesticide-related toxicity.

Background/Objectives: Previously, we showed that blood-based polarizing cardioplegia exerted beneficial cardioprotection during hypothermic ischemia; however, these positive effects of blood-based polarizing cardioplegia were reduced during normothermic ischemia compared to blood-based hyperkalemic (depolarizing) cardioplegia. This study compares crystalloid polarizing cardioplegia to crystalloid depolarizing cardioplegia in a normothermic porcine model of cardiopulmonary bypass; Methods: Twelve pigs were randomized to receive either normothermic polarizing (n = 7) or depolarizing (n = 5) crystalloid cardioplegia. After the initiation of cardiopulmonary bypass, normothermic arrest (34 °C, 60 min) was followed by 60 min of on-pump and 90 min of off-pump reperfusion. Myocardial injury (arterial CK-MB), hemodynamic function, and the energy status of the hearts were measured; Results: The arterial release of CK-MB was comparable between groups (p = 0.78) during reperfusion. During 150 min of reperfusion, systolic left ventricular pressure (p = 0.01) and coronary flow (p = 0.009) were increased, and wedge pressure (p = 0.04) was decreased in the polarized group. Further hemodynamic parameters (cardiac output, stroke volume) and high-energy phosphate levels were similar between groups. The requirement for noradrenaline administration during reperfusion was significantly higher (p = 0.013) in the polarized group; Conclusions: Under normothermic conditions and despite a similar increase in levels of cardiac CK-MB, crystalloid polarizing cardioplegia protected systolic and diastolic cardiac function after 60 min of cardiac arrest. These results suggest beneficial effects for polarizing cardioplegia; clinical studies are required to confirm these effects. [ABSTRACT FROM AUTHOR]

Technical assistance (TA) has long been a strategy utilized to support implementation of a range of different evidence-based interventions within clinical, community and other service settings. Great progress has come in extending the evidence base to support TA's use across multiple contexts, the result of more extensive categorizing of implementation strategies to support systematic studies of their effectiveness in facilitating successful implementation. This commentary builds on that progress to suggest several opportunities for future investigation and collaborative activity among researchers, practitioners, policymakers and other key decision-makers in hopes of continuing to build the success highlighted in this special issue and elsewhere. Authors call for increased attention to operationalization and tailoring of TA, considering how TA services can be sustained over time and how to consider externally-provided TA versus that housed within an organization. In addition, the commentary suggests a few key areas for capacity-building that can increase the quality, reach, and impact of TA for the future. [ABSTRACT FROM AUTHOR]

Background: As dentistry became a profession it crafted aspirational values to announce the highest standards for the relationship between individual practitioners and those who sought their care and of professional etiquette among colleagues. These standards evolved as dentistry underwent dramatic development in technique, scientific knowledge, commercial ownerships of practice, a shift toward insurance and the government paying for most of the dental bill, and an increasing voice for the public. Dentistry borrowed some of the principles from the bioethics movement in the 1970s and '80s. Objective: Evidence is presented in this paper for six areas showing that measures of ethical impact such as public trust, disciplined licenses, teaching of ethics, and membership in organized dentistry suggest that further adjustments are needed to make the profession responsive to the current expectations of society and the profession itself. Conclusion: An alternative to the descriptive lists of aspirational principles is presented. This involves two imperatives or expected types of behavior that close the gap between ideal images and typical behavior. Practical Highlights: Moral action and professionalism (MAP) means not cheating, which is taking unjustified personal advantage of others, and being stewards of the common good that is the mark of a profession. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to establish the potential therapeutic profile of neutrophil‐derived extracellular vesicles (EVs) in experimental inflammatory arthritis and associate pharmacological activity with specific EV components, focusing on microRNAs. Methods: Neutrophil EVs were administered intra‐articularly through a prophylactic or therapeutic protocol to male C57BL/6 mice undergoing serum‐transfer–induced inflammatory arthritis. Transcriptomic analysis of knees was performed on joints following EV administration, naive and arthritic mice (untreated; n = 4/group) and EV‐treated diseased mice (intra‐articular administration) with contralateral (vehicle‐treated; n = 8/group). Comparison of healthy donor and patients with rheumatoid arthritis (RA) neutrophil EVs was performed. Results: EVs afforded cartilage protection with an increase in collagen‐II and reduced collagen‐X expression within the joint. To gain mechanistic insights, RNA sequencing of the arthritic joints was conducted. A total of 5,231 genes were differentially expressed (P < 0.05), with 257 unique to EV treatment. EVs affected key regenerative pathways involved in joint development, including Wnt and Notch signaling. This wealth of genomic alteration prompted to identify microRNAs in EVs, 10 of which are associated with RA. As a proof of concept, we focused on miR‐455‐3p, which was detected in both healthy donor and RA EVs. EV addition to chondrocyte cultures elevated miR‐455‐3p and exerted anticatabolic effects upon interleukin‐1β stimulation; these effects were blocked by actinomycin or miR‐455‐3p antagomir. Conclusion: Neutrophils from patients with RA yielded EVs with composition, efficacy, and miR‐455‐3p content similar to those of healthy volunteers, suggesting that neutrophil EVs could be developed as an autologous treatment to protect and repair joint tissue of patients affected by inflammatory arthritides. [ABSTRACT FROM AUTHOR]

Neuropathic pain remains poorly managed by current therapies, highlighting the need to improve our knowledge of chronic pain mechanisms. In neuropathic pain models, dorsal root ganglia (DRG) nociceptive neurons transfer miR-21 packaged in extracellular vesicles to macrophages that promote a proinflammatory phenotype and contribute to allodynia. Here we show that miR-21 conditional deletion in DRG neurons was coupled with lack of upregulation of chemokine CCL2 after nerve injury and reduced accumulation of CCR2-expressing macrophages, which showed TGF-[beta]-related pathway activation and acquired an M2-like antinociceptive phenotype. Indeed, neuropathic allodynia was attenuated after conditional knockout of miR-21 and restored by TGF-[beta]R inhibitor (SB431542) administration. Since TGF-[beta]R2 and TGF-[beta]1 are known miR- 21 targets, we suggest that miR-21 transfer from injured neurons to macrophages maintains a proinflammatory phenotype via suppression of such an antiinflammatory pathway. These data support miR-21 inhibition as a possible approach to maintain polarization of DRG macrophages at an M2-like state and attenuate neuropathic pain., Introduction Peripheral neuropathy is a debilitating condition that often leads to severe and chronic neuropathic pain, for which novel treatment strategies are needed because current drugs have limited efficacy and [...]

Summary: Clean cooking has emerged as a major concern for global health and development because of the enormous burden of disease caused by traditional cookstoves and fires. The World Health Organization has developed new indoor air quality guidelines that few homes will be able to achieve without replacing traditional methods with modern clean cooking technologies, including fuels and stoves. However, decades of experience with improved stove programs indicate that the challenge of modernizing cooking in impoverished communities includes a complex, multi-sectoral set of problems that require implementation research. The National Institutes of Health, in partnership with several government agencies and the Global Alliance for Clean Cookstoves, has launched the Clean Cooking Implementation Science Network that aims to address this issue. In this article, our focus is on building a knowledge base to accelerate scale-up and sustained use of the cleanest technologies in low- and middle-income countries. Implementation science provides a variety of analytical and planning tools to enhance effectiveness of clinical and public health interventions. These tools are being integrated with a growing body of knowledge and new research projects to yield new methods, consensus tools, and an evidence base to accelerate improvements in health promised by the renewed agenda of clean cooking.