The Plasticene era: Current uncertainties in estimates of the hazards posed by tiny plastic particles on soils and terrestrial invertebrates.

Plastics are ubiquitous in our daily life. Large quantities of plastics leak in the environment where they weather and fragment into micro- and nanoparticles. This potentially releases additives, but rarely leads to a complete mineralization, thus constitutes an environmental hazard. Plastic pollution in agricultural soils currently represents a major challenge: quantitative data of nanoplastics in soils as well as their effects on biodiversity and ecosystem functions need more attention. Plastic accumulation interferes with soil functions, including water dynamics, aeration, microbial activities, and nutrient cycling processes, thus impairing agricultural crop yield. Plastic debris directly affects living organisms but also acts as contaminant vectors in the soils, increasing the effects and the threats on biodiversity. Finally, the effects of plastics on terrestrial invertebrates, representing major taxa in abundance and diversity in the soil compartment, need urgently more investigation from the infra-individual to the ecosystem scales.

The Opioid Response Project: An Effective Learning Collaborative for Local Communities?

The Opioid Response Project (ORP) was designed as an intensive 2-year health promotion learning collaborative grounded in the Collective Impact Model (CIM) to prepare ten local communities to address the opioid crisis. The purpose of this evaluation was to describe the ORP implementation, provide a summary of the evaluation results, share insights, and discuss implications. Results were informed by multiple data sources, including project documents, surveys, and interviews with members of the ORP and community teams. Based on process evaluation results, 100% of community teams reported being satisfied with the ORP and recommended this experience to others. ORP participation outputs ranged from new opioid response programs, to strengthened community teams, to receipt of additional funding. Based on the outcome evaluation, the ORP was effective at increasing community knowledge and capacity, promoting collaboration, and facilitating sustainability. This initiative is an example of an effective learning collaborative to curb the opioid epidemic at the community level. Participating communities found great value in working together as part of a larger cohort and reported benefits from the peer learning and support provided by the ORP. In particular, access to technical assistance, identification of engagement strategies within and across community teams, and a focus on sustainability are key practice components to be included in learning collaboratives designed to address large-scale public health issues.

Anxious-Withdrawal and Sleep Problems during Adolescence: The Moderating Role of Peer Difficulties.

Anxious-withdrawal is a well-established individual risk factor for psychosocial difficulties during adolescence. It is unknown, however, whether it also places youth at increased risk for physical health problems, such as sleep difficulties. This study examines the concurrent and prospective associations between anxious-withdrawal and six types of sleep difficulties (i.e., sleeping too much, sleeping too little, talking/walking in sleep, being overtired, nightmares, and general trouble sleeping). We further evaluate whether these associations differ for adolescents who are high versus low in exclusion and victimization. The participants were 395 adolescents (Mage = 13.61 years; 35% ethnic minority) who completed peer nominations of anxious-withdrawal, exclusion, and victimization at Time 1 (T1). Their mothers completed reports of sleep difficulties at T1 and at Time 2 (T2). Path analyses revealed unique associations between anxious-withdrawal and several types of sleep difficulties (e.g., sleeping too much) at T1. Analyses also revealed a significant interaction effect between T1 anxious-withdrawal and exclusion/victimization such that anxious-withdrawal was prospectively associated with trouble sleeping only for those young adolescents who are highly excluded/victimized. Our findings are the first to link anxious-withdrawal to a physical health outcome in adolescence and point to the need for future research to not only examine anxious-withdrawal and physical health but also to include assessments of peer difficulties.

In vitro-generated human muscle reserve cells are heterogeneous for Pax7 with distinct molecular states and metabolic profiles.

BACKGROUND: The capacity of skeletal muscles to regenerate relies on Pax7+ muscle stem cells (MuSC). While in vitro-amplified MuSC are activated and lose part of their regenerative capacity, in vitro-generated human muscle reserve cells (MuRC) are very similar to quiescent MuSC with properties required for their use in cell-based therapies. METHODS: In the present study, we investigated the heterogeneity of human MuRC and characterized their molecular signature and metabolic profile. RESULTS: We observed that Notch signaling is active and essential for the generation of quiescent human Pax7+ MuRC in vitro. We also revealed, by immunofluorescence and flow cytometry, two distinct subpopulations of MuRC distinguished by their relative Pax7 expression. After 48 h in differentiation medium (DM), the Pax7High subpopulation represented 35% of the total MuRC pool and this percentage increased to 61% after 96 h in DM. Transcriptomic analysis revealed that Pax7High MuRC were less primed for myogenic differentiation as compared to Pax7Low MuRC and displayed a metabolic shift from glycolysis toward fatty acid oxidation. The bioenergetic profile of human MuRC displayed a 1.5-fold decrease in glycolysis, basal respiration and ATP-linked respiration as compared to myoblasts. We also observed that AMPKα1 expression was significantly upregulated in human MuRC that correlated with an increased phosphorylation of acetyl-CoA carboxylase (ACC). Finally, we showed that fatty acid uptake was increased in MuRC as compared to myoblasts, whereas no changes were observed for glucose uptake. CONCLUSIONS: Overall, these data reveal that the quiescent MuRC pool is heterogeneous for Pax7 with a Pax7High subpopulation being in a deeper quiescent state, less committed to differentiation and displaying a reduced metabolic activity. Altogether, our data suggest that human Pax7High MuRC may constitute an appropriate stem cell source for potential therapeutic applications in skeletal muscle diseases.

Community Pharmacy Recruitment for Practice-Based Research: Challenges and Lessons Learned.

To support the successful integration of community pharmacies into value-based care models, research on the feasibility and effectiveness of novel pharmacist-provided patient care services is needed. The UNC Eshelman School of Pharmacy, supported by the National Association of Chain Drug Stores (NACDS) Foundation, designed the Community-based Valued-driven Care Initiative (CVCI) to (1) identify effective value-based patient care interventions that could be provided by community pharmacists, (2) implement and evaluate the feasibility of the selected patient care interventions, and (3) develop resources and create collaborative sustainability opportunities. The purpose of this manuscript is to describe recruitment strategies for CVCI and share lessons learned. The project team identified pharmacies for recruitment through a mixed data analysis followed by a "fit" evaluation. A total of 42 pharmacy organizations were identified for recruitment, 24 were successfully contacted, and 9 signed on to the project. During recruitment, pharmacies cited concerns regarding the financial sustainability of implementing and delivering the patient care services, challenges with staffing and infrastructure, and pharmacists' comfort level. To foster participation, it was vital to have leadership buy-in, clear benefits from implementation, and assured sustainability beyond the research period.

Readiness as a precursor of early implementation outcomes: an exploratory study in specialty clinics.

BACKGROUND: Readiness has been identified as an essential precursor of successful implementation. However, evidence supporting its value is sparse. Empirical studies exploring the relationship between the application of readiness interventions, readiness levels, and implementation outcomes are lacking. The purpose of this study was twofold: (1) to evaluate the effectiveness of a readiness intervention (based on increases in readiness levels, changes in early implementation outcomes (i.e., acceptability, appropriateness, feasibility, and intent to adopt), and qualitative insights into the types of perceived outcomes) and (2) to assess the role of readiness as a predictor of these early implementation outcomes. METHODS: Seven healthcare specialty clinics engaged in a structured process to assess and build readiness for implementing a comprehensive medication management (CMM) service over a 10-month period. A mixed methods approach, which included surveys with healthcare stakeholders at each clinic (N = 27) and interviews with the lead pharmacists (N = 7), was used to evaluate the effectiveness of the readiness intervention (aim 1). Survey data were also used to conduct multiple regression models to assess the role of readiness as a predictor of early acceptability, appropriateness, feasibility, and intent to adopt CMM (aim 2). RESULTS: Significantly higher readiness levels, as well as higher scores on acceptability, appropriateness, feasibility, and intent to adopt, were reported as a result of engaging in the readiness intervention. However, upon closer examination, the direction of this association seemed to be dependent on the type of clinic. Qualitative data on the types of perceived outcomes resulting from engaging in the readiness intervention provided further insights into the potential reasons for these findings. Furthermore, post-readiness levels predicted between 44 and 68% of the variance in the early implementation outcomes. When accounting for clinic membership, readiness remained critical for service acceptability, feasibility, and intent to adopt but not for appropriateness. CONCLUSION: These findings provide insights into the relationship between use of a readiness intervention, readiness levels, and early implementation outcomes. Engaging healthcare settings in a readiness intervention was beneficial in ways more complex than a simple positive linear relationship, highlighting the opportunity to broaden its purpose and expand definitions of readiness success. In addition, the importance of readiness levels in predicting early implementation outcomes, while critical, also seems to be highly dependent on context, particularly for appropriateness (fit).

Performance-based pharmacy payment models: key components and critical implementation considerations for successful uptake and integration.

BACKGROUND: In the United States, the shift towards value-based health care seeks to improve patient outcomes while reducing health care spending. Although the federal government has led the implementation of performance-based models for physicians and health care systems, commercial entities have largely been responsible for the development of similar models within pharmacy. For the purposes of this study, performance-based pharmacy payment models (PBPPMs) were defined as prescription drug payment models that determine reimbursement or fees for community pharmacies based in part on measured performance. These PBPPMs incentivize pharmacies to improve patient care by linking reimbursement to performance measures. However, the design and implementation of PBPPMs lack transparency and have not been described in the literature. OBJECTIVES: To (1) describe the structure of PBPPMs in the United States and (2) identify contextual and motivational influences that need to be considered for successful uptake and integration of these models. METHODS: A search of peer-reviewed and grey literature was undertaken. In addition, semi-structured stakeholder interviews were conducted with a convenience sample of 17 individuals who were community pharmacists, payers, quality measure developers and vendors, academics, and pharmacy advocacy organization leaders. Data were analyzed to understand the current structure of PBPPMs and opportunities for improvement, as well as implementation considerations that included facilitators, barriers, and key insights. RESULTS: This study identified 4 major components of US PBPPMs: attribution, performance and quality measures, incentive structures, and patient care services. A number of barriers (eg, lack of alignment) and recommendations to improve the current structure of PBPPMs (eg, the need for adequate incentives to facilitate change) were highlighted. Notable implementation considerations centered around (1) establishing common ground among stakeholders to avoid misalignment and encourage engagement; (2) the importance of a quality-driven, innovative, and flexible organizational culture with access to data infrastructure, adjusted workflows, and relevant trainings; (3) supporting the cultural transition to value-based health care; and (4) application of financial incentives at the pharmacy or pharmacist level. CONCLUSIONS: To better develop and implement PBPPMs, it is first critical to understand the key components that define these models and the needed changes to their structure. In addition, identifying the contextual and motivational factors that influence their successful integration can improve future uptake. This study illustrates the landscape of PBPPMs in the United States, as well as makes recommendations for improvement in their design. To improve future development and implementation of these models, the following recommendations are highlighted: (1) increase transparency and alignment of measures with the incentive structure; (2) embrace innovative business models; (3) carefully plan and use roadmaps that outline successful uptake and implementation; and (4) foster culture of quality at all levels of health care. DISCLOSURES: This study was sponsored by Pharm-Alliance, an alliance between the pharmacy schools of the University of North Carolina at Chapel Hill, Monash University, and University College London. Urick reports consulting fees from Pharmacy Quality Solutions and Cardinal Health, unrelated to this work. The other authors have nothing to disclose. This study was a podium presentation under the title "What Makes Performance-Based Pharmacy Payment Models Work?" at AMCP Nexus Virtual, October 2020.

Measuring implementation of medication optimization services: Development and validation of an implementation outcomes questionnaire.

BACKGROUND: Implementation outcomes serve as progress and success indicators of the implementation process. They are also key antecedents to achieving the more traditional clinical outcomes typically associated with a service. Despite their importance, there are few implementation outcomes measures with appropriate psychometric properties, none of which have yet been adapted for medication optimization services. OBJECTIVES: This study aims to develop and validate the Implementation Outcomes Questionnaire (IOQ) to assess implementation of medication optimization services, starting with Comprehensive Medication Management (CMM). The resulting IOQ is a 40-item self-report instrument for six implementation outcomes, including adoption, acceptability, feasibility, appropriateness, penetration, and sustainability. METHODS: A three-phase approach was used to develop and validate the IOQ. Development of the instrument, Phase I, was informed by a targeted search of existing implementation outcomes measures in other fields, a review of suitableoptions options by an expert panel, and item adaptation. To assess content validity, Phase II, an internal vetting process was conducted using an adapted version of Rubio and colleagues' methodology. Evidence of reliability and construct validity, Phase III, was obtained through a pilot test with 167 pharmacists within 78 different care settings. RESULTS: Overall, the results supported the reliability and validity (both content and construct) of the IOQ, with further psychometric testing needed for adoption. The items' relevance, clarity, and alignment with each implementation concept were high, except for Penetration. As a result, the Penetration items were refined for further use. Best-fit models were identified for each outcome based on the MCFA analyses, thereby providing insights into the factor structures and interpretation for each measure. Cronbach' alphas indicated good internal consistency. CONCLUSIONS: This questionnaire is the first of its kind tailored to medication optimization services, starting with CMM. Access to this survey should facilitate measurement of implementation outcomes, thereby increasing the likelihood of achieving the desired clinical outcomes.

Purified IgG from aquaporin-4 neuromyelitis optica spectrum disorder patients alters blood-brain barrier permeability.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is a primary astrocytopathy driven by antibodies directed against the aquaporin-4 water channel located at the end-feet of the astrocyte. Although blood-brain barrier (BBB) breakdown is considered one of the key steps for the development and lesion formation, little is known about the molecular mechanisms involved. The aim of the study was to evaluate the effect of human immunoglobulins from NMOSD patients (NMO-IgG) on BBB properties. METHODS: Freshly isolated brain microvessels (IBMs) from rat brains were used as a study model. At first, analysis of the secretome profile from IBMs exposed to purified NMO-IgG, to healthy donor IgG (Control-IgG), or non-treated, was performed. Second, tight junction (TJ) proteins expression in fresh IBMs and primary cultures of brain microvascular endothelial cells (BMEC) was analysed by Western blotting (Wb) after exposition to NMO-IgG and Control-IgG. Finally, functional BBB properties were investigated evaluating the presence of rat-IgG in tissue lysate from brain using Wb in the rat-model, and the passage of NMO-IgG and sucrose in a bicameral model. RESULTS: We found that NMO-IgG induces functional and morphological BBB changes, including: 1) increase of pro-inflammatory cytokines production (CXCL-10 [IP-10], IL-6, IL-1RA, IL-1ß and CXCL-3) in IBMs when exposed to NMO-IgG; 2) decrease of Claudin-5 levels by 25.6% after treatment of fresh IBMs by NMO-IgG compared to Control-IgG (p = 0.002), and similarly, decrease of Claudin-5 by at least 20% when BMEC were cultured with NMO-IgG from five different patients; 3) a higher level of rat-IgG accumulated in periventricular regions of NMO-rats compared to Control-rats and an increase in the permeability of BBB after NMO-IgG treatment in the bicameral model. CONCLUSION: Human NMO-IgG induces both structural and functional alterations of BBB properties, suggesting a direct role of NMO-IgG on modulation of BBB permeability in NMOSD.

Ready, set, go!: exploring use of a readiness process to implement pharmacy services.

BACKGROUND: Readiness is an essential precursor of successful implementation; however, its conceptualization and application has proved elusive. R = MC2 operationalizes readiness for use in practice. The purpose of this study was to (1) describe the application of R = MC2 to assess and build readiness in nine healthcare sites responsible for implementing medication management services and (2) gain insights into the sites' experience. METHODS: This mixed methods exploratory study used data collected as part of a process evaluation. Understanding application of the readiness process (Aim 1) involved examining team members' involvement (who?), readiness challenges and readiness building strategies (what?), strategy execution (how much?), and resulting changes (for what purpose?). To understand the sites' experience with the R = MC2 system (Aim 2), interviews were conducted with six of the sites to identify facilitators, barriers, and lessons learned. Data sources included a document review (e.g., sites' action plans), survey results, and interview data. RESULTS: Sites included primary care and specialty clinics, pharmacies within health systems, and community pharmacies. Teams consisted of 4-11 members, including a lead pharmacist. The teams' readiness activities clustered into five broad categories of readiness building strategies (e.g., building the operational infrastructure for service integration). Of the 34 strategies identified across sites, 68% were still in progress after 4 months. Engaging in the readiness process resulted in a number of outputs (e.g., data management systems) and benefits (e.g., an opportunity to ensure alignment of priorities and fit of the intervention). Based on the interviews, facilitators of the readiness process included assistance from a coach, internal support, and access to the readiness tools. Competing priorities and lack of resources, timely decision-making, and the timing of the readiness process were cited as barriers. The importance of service fit, stakeholder engagement, access to a structured approach, and rightsizing the readiness process emerged as lessons learned. CONCLUSIONS: These findings provide valuable insights into the application of a readiness process. If readiness is to be integrated into routine practice as part of any implementation effort, it is critical to gain a better understanding of its application and value.

Connexins in neuromyelitis optica: a link between astrocytopathy and demyelination.

Neuromyelitis optica, a rare neuroinflammatory demyelinating disease of the CNS, is characterized by the presence of specific pathogenic autoantibodies directed against the astrocytic water channel aquaporin 4 (AQP4) and is now considered as an astrocytopathy associated either with complement-dependent astrocyte death or with astrocyte dysfunction. However, the link between astrocyte dysfunction and demyelination remains unclear. We propose glial intercellular communication, supported by connexin hemichannels and gap junctions, to be involved in demyelination process in neuromyelitis optica. Using mature myelinated cultures, we demonstrate that a treatment of 1 h to 48 h with immunoglobulins purified from patients with neuromyelitis optica (NMO-IgG) is responsible for a complement independent demyelination, compared to healthy donors' immunoglobulins (P < 0.001). In parallel, patients' immunoglobulins induce an alteration of connexin expression characterized by a rapid loss of astrocytic connexins at the membrane followed by an increased size of gap junction plaques (+60%; P < 0.01). This was co-observed with connexin dysfunction with gap junction disruption (-57%; P < 0.001) and increased hemichannel opening (+17%; P < 0.001), associated with glutamate release. Blocking connexin 43 hemichannels with a specific peptide was able to prevent demyelination in co-treatment with patients compared to healthy donors' immunoglobulins. By contrast, the blockade of connexin 43 gap junctions with another peptide was detrimental for myelin (myelin density -48%; P < 0.001). Overall, our results suggest that dysregulation of connexins would play a pathogenetic role in neuromyelitis optica. The further identification of mechanisms leading to connexin dysfunction and soluble factors implicated, would provide interesting therapeutic strategies for demyelinating disorders.

In the eye of the swiper: a preliminary analysis of the relationship between dating app use and dimensions of body image.

BACKGROUND: Dating apps are largely visual platforms and based on evaluations of the attractiveness of users. Thus, engaging with this type of social media may be associated with body image concerns. OBJECTIVE: This study aimed to explore the relationship between dating app use and body image. METHODS: College students (n = 170, 50% females) reported on dating app use, as well as body shame, surveillance, body satisfaction, media ideal internalization, and controllability beliefs related to weight/shape. RESULTS: Among males, frequent checking of dating apps was positively correlated with body shame and negatively with beliefs regarding weight/shape controllability. Media internalization was negatively correlated with experiencing negative feelings when using dating apps, and positively with positive feelings. Few associations emerged among females. CONCLUSION: Dating app use seems most tightly associated with body image concerns among males. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Getting Real about body image: A qualitative investigation of the usefulness of the Aerie Real campaign.

This study qualitatively examined perceptions of the Aerie Real campaign that utilized images that had not been digitally modified, as well as its capacity to contribute to positive body image. A sample of 35 college women, of mean age of 19.48 (range = 18-23 years) participated in individual interviews focused on their perceptions and reactions to the images included in the Aerie Real campaign. They also described the impact of the campaign on their brand perceptions and consumer intentions, as well as their attitudes towards social policy targeting the use of digital airbrushing. Most participants reacted to the images positively and perceived them as representing body diversity across several dimensions. In addition, the majority of participants found the images to be helpful for promoting positive body image and acceptance, through both appearance comparisons, and the modeling of body confidence. In addition, many participants expressed being more likely to purchase products from Aerie and support for the brand. Overwhelmingly, participants called for widespread portrayals of diverse bodies in media, although only partial support emerged for achieving this through policy. These findings support the usefulness of increasing body diversity in media and limiting thin-ideal images as means of promoting positive body image.

Alveolar liquid clearance in lung injury: Evaluation of the impairment of the ß2-adrenergic agonist response in an ischemia-reperfusion lung injury model.

While alveolar liquid clearance (ALC) mediated by the ß2-adrenergic receptor (ß2-AR) plays an important role in lung edema resolution in certain models of lung injury, in more severe lung injury models, this response might disappear. Indeed, we have shown that in an ischemia-reperfusion-induced lung injury model, ß2-agonists do not enhance ALC. The objective of this study was to determine if downregulation of the ß2-AR could explain the lack of response to ß2-agonists in this lung injury model. In an in vivo canine model of lung transplantation, we observed no change in ß2-AR concentration or affinity in the injured transplanted lungs compared to the native lungs. Furthermore, we could not enhance ALC in transplanted lungs with dcAMP + aminophylline, a treatment that bypasses the ß2-adrenergic receptor and is known to stimulate ALC in normal lungs. However, transplantation decreased αENaC expression in the lungs by 50%. We conclude that the lack of response to ß2-agonists in ischemia-reperfusion-induced lung injury is not associated with significant downregulation of the ß2-adrenergic receptors but is attributable to decreased expression of the ENaC channel, which is essential for sodium transport and alveolar liquid clearance in the lung.

Prevalence and impact of pain on the quality of life of lung transplant recipients: a prospective observational study.

STUDY OBJECTIVE: To study the prevalence and impact of pain on the quality of life (QOL) of lung transplant recipients. DESIGN AND PATIENTS: Prospective, observational, cross-sectional study. Ninety-six lung transplant recipients (> 3 months after transplantation) completed questionnaires measuring the severity and impact of pain (Brief Pain Inventory), anxiety (State Trait Anxiety Inventory), QOL (Short Form-36 version 2 [SF-36v2]), and depression (Beck Depression Inventory [BDI]). SETTING: University medical center lung transplant outpatient clinic. RESULTS: The prevalence of pain in lung transplant recipients was 49%. Patients with pain were older, more likely to have undergone unilateral lung transplantation (64% vs 40%, p = 0.03), and were more likely to have lung emphysema (55% vs 38%, p = 0.004). Only a pulmonary diagnosis of lung emphysema remained an independent predictor for postoperative pain in a logistic regression model. Average (+/- SD) score of the BDI was 9.6 +/- 7.8 and 5.8 +/- 5.8 (p = 0.005) for patients with and without pain, respectively. Patients with and without pain did not significantly differ in terms of anxiety. Pain-free patients had a significantly higher physical component score than patients with pain in the SF-36v2 (mean, 48.7 +/- 8.6 vs 38.6 +/- 9.8, p < 0.0001, respectively), while the mental component scores were not statistically different between the two groups. CONCLUSIONS: Lung transplant recipients have a high prevalence of pain. Patients with lung emphysema as their preoperative diagnosis are more likely to have pain. The occurrence of pain is associated with a decreased QOL in lung transplant recipients.

Acute postoperative pain in lung transplant recipients.

BACKGROUND: This retrospective study was designed to assess the quality of postoperative pain control and the facility of transition from epidural to oral analgesia in lung transplant recipients. METHODS: After institutional review board approval, data were collected from the charts of all patients who underwent lung transplantation at our institution between 1998 and 2002. The study group consisted of the patients for whom an epidural was the first postoperative pain management modality. To serve as a control group we reviewed the charts of 30 patients, randomly selected over the same period, who underwent a thoracotomy for indications other than transplantation and who received postoperative epidural analgesia. RESULTS: Eighty-three patients were available for analysis. Unilateral and bilateral lung transplant recipients had equivalent quality of pain control. However, lung transplant recipients had a lower incidence of adequate pain relief than patients undergoing thoracotomy for other indications (73% vs 87%, p < 0.05). Lung transplant recipients also had a higher incidence of epidural to oral analgesia transition failure (47% vs 20%, p < 0.01). CONCLUSIONS: This is the first study to assess the quality of postoperative pain control and success of transition from epidural to oral analgesia in lung transplant recipients. Prospective studies are needed to assess the impact of our findings on patients' outcome.