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PurposeThe U.S. federal Earned Income Tax Credit (EITC) is often considered the most effective antipoverty program for families in the U.S., leading to a variety of improved outcomes such as educational attainment, work incentives, economic activity, income, and health benefits for mothers, infants and children. State EITC supplements to the federal credit can significantly enhance the magnitude of this intervention. In this paper we advance EITC and health research by: 1) describing the diffusion of state EITC policies over 40 years, 2) presenting patterns in important EITC policy dimensions across space and time, and 3) disseminating a robust data set to advance future research by policy analysts and scientists.MethodsWe used current public health law research methods to systematically collect, conduct textual legal analysis, and numerically code all EITC legislative changes from 1980 through 2020 in the 50 states and Washington, D.C.ResultsFirst, the pattern of diffusion across states and time shows initial introductions during the 1990s in the Midwest, then spreading to the Northeast, with more recent expansions in the West and South. Second, differences by state and time of important policy dimensions are evident, including size of credit and refundability. Third, state EITC benefits vary considerably by household structure.ConclusionContinued research on health outcomes is warranted to capture the full range of potential beneficial effects of EITCs on family and child wellbeing. Lawyers and policy analysts can collaborate with epidemiologists and economists on other high-quality empirical studies to assess the many dimensions of policy and law that potentially affect the social determinants of health.

Hydrogen sulphide (H2S), nitric oxide (NO), and carbon monoxide (CO) are involved in transitional microvascular tone dysregulation in the preterm infant; however there is conflicting evidence on the interaction of these gasotransmitters, and their overall contribution to the microcirculation in newborns is not known. The aim of this study was to measure the levels of all 3 gasotransmitters, characterise their interrelationships and elucidate their combined effects on microvascular blood flow.90 preterm neonates were studied at 24h postnatal age. Microvascular studies were performed by laser Doppler. Arterial COHb levels (a measure of CO) were determined through co-oximetry. NO was measured as nitrate and nitrite in urine. H2S was measured as thiosulphate by liquid chromatography. Relationships between levels of the gasotransmitters and microvascular blood flow were assessed through partial correlation controlling for the influence of gestational age. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow and derive a theoretical model of their interactions.No relationship was observed between NO and CO (p = 0.18, r = 0.18). A positive relationship between NO and H2S (p = 0.008, r = 0.28) and an inverse relationship between CO and H2S (p = 0.01, r = -0.33) exists. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow. The model with the best fit is presented.The relationships between NO and H2S, and CO and H2S may be of importance in the preterm newborn, particularly as NO levels in males are associated with higher H2S levels and higher microvascular blood flow and CO in females appears to convey protection against vascular dysregulation. Here we present a theoretical model of these interactions and their overall effects on microvascular flow in the preterm newborn, upon which future mechanistic studies may be based.

All organisms age, the rate of which can be measured by demographic analysis of mortality rates. The rate of ageing is thermally sensitive in ectothermic invertebrates and we examined the effects of temperature on both demographic rates of ageing and on cellular senescence in the blowfly, Calliphora stygia. The short lifespan of these flies is advantageous for demographic measurements while their large body size permits individual-based biochemical characterisation. Blowflies maintained at temperatures from 12°C to 34°C had a five to six-fold decrease in maximum and average longevity, respectively. Mortality rates were best described by a two-phase Gompertz relation, which revealed the first-phase of ageing to be much more temperature sensitive than the second stage. Flies held at low temperatures had both a slower first-phase rate of ageing and a delayed onset of second-phase ageing, which significantly extended their longevity compared with those at high temperatures. Blowflies that were transferred from 29°C to 15°C had higher first-phase mortality rates than those of flies held at constant 15°C, but their onset of second-phase ageing was deferred beyond that of flies held constantly at this temperature. The accumulation of fluorescent AGE pigment, a measure of cellular oxidative damage, increased steadily over time in all blowflies, irrespective of the temporal pattern of mortality. Pigment accumulated steadily during periods of 'negligible senescence', as measured by minimal rate of mortality, and the rate of accumulation was significantly affected by temperature. Thus accumulation of AGE pigment is more representative of chronological age than a reflection of biological age or a cause of mortality.

The current study investigates secondary teachers’ understandings of student engagement in relation to three dimensions (behavioural, emotional and cognitive engagement). It is posited that there exists an order in which dimensions of engagement must develop in order to facilitate students’ engagement in the classroom. However, there is a lack of research exploring the understandings of the very people who create students’ learning environment: teachers. The aim of the current paper is to establish if teachers believe that one dimension exists as a catalyst for the other dimensions of engagement in student learning. This article reports on novel qualitative findings from interviews with secondary teachers (n = 11). Findings indicated that teachers do consider students’ behavioural or emotional or cognitive engagement as a precursor, or catalyst, to other dimensions of engagement. However, there is not an agreed order, and some teachers’ approaches are influenced by contextual considerations. These findings contribute new insights to existing research into teachers’ understandings and implementation of strategies to support student engagement in learning.

As the COVID-19 pandemic sweeps the globe, many veterans with substance use issues have faced the closure of treatment facilities, mandates to shelter in place, and social distancing measures. To better understand their pandemic experiences, substance use changes, and functioning, a survey was nationally administered to a sample of United States veterans reporting substance use issues during the pandemic. The purpose of this cross-sectional online survey for veterans (N = 409) was to report on COVID-19 experiences, safety behaviors, and infection experiences while also investigating the relationship among addictive behaviors, mental and physical health, and COVID-19 impact. Measures also assessed specific substance use concerns, pandemic-related loneliness, and functioning. Though few veterans reported personally receiving a confirmed COVID-19 medical diagnosis (10.5%), the impact of pandemic stressors was evident, with a majority reporting anxiety related to contracting COVID-19 (61.4%) or fear of a family member or close friend contracting COVID-19 (58.7%). Participants reported increased use of alcohol (45.3%), sedatives (36.6%), inhalants (35.7%), tobacco (35.0%), and cannabis (34.9%), attributed specifically to the pandemic. Regression analyses revealed that even when controlling for the contribution of problematic substance use issues, negative pandemic impacts and self-reported COVID-19 related loneliness were related to more impaired physical and mental health functioning during the pandemic. Findings from this sample of veterans with addiction issues add to the growing literature suggesting unique and adverse effects of COVID-19 stressors on functioning while also revealing specific pandemic impacts for this group.

Abstract Background There is a strong interest in the concept of developmental origins of health and disease and their influence on various factors “from cradle to grave”. Despite the increasing appreciation of this lifelong legacy across the human life course, many gaps remain in the scientific understanding of mechanisms influencing these formative phases. Cross-generational susceptibility to health problems is emerging as a focus of research in the context of birth cohort studies. The primary aim of the Illawarra Born study is to make scientific discoveries associated with improving health and wellbeing across the lifespan, with a particular focus on preventable chronic diseases, especially mental health. This birth cohort study will follow and collect data from three cohorts representing different stages across the lifespan: infants, adults (parents) and older adults (grandparents). The multi-generational, cross-sectional and longitudinal design of this birth cohort study supports a focus on the contributions of genetics, environment and lifestyle on health and wellbeing. The feasibility of conducting a multi-generational longitudinal birth cohort project was conducted through a small pilot study. Methods/design The purpose of this paper is to report on the feasibility and acceptability of the research protocol for a collaborative cross-generation health study in the community and test recruitment and outcome measures for the main study. This feasibility study included pregnant women who were intending to give birth in the Illawarra-Shoalhaven region in Eastern Australia. The area includes a large, regional referral hospital, with capacity to treat specialist and complex cases. Pregnant women were asked to participate in five data collection waves beginning at 22 weeks gestation and ending with a 6-month post-partum appointment. Recruitment was then extended, via the pregnant women, to also include fathers and maternal grandmothers. Discussion This feasibility study focused on the perinatal period and collected data across three multi-disciplinary domains including mental health, diet, exposures to toxins and the role of these in maternal and infant outcomes. Forty-one families participated in extensive data collection from 22 weeks gestation to 6-months post-partum. Factors impacting on viability and feasibility including recruitment solutions provide the basis for a large-scale study.

Abstract Recent studies have indicated that the C4 perennial bioenergy crops switchgrass (Panicum virgatum) and big bluestem (Andropogon gerardii) accumulate significant amounts of soil carbon (C) owing to their extensive root systems. Soil C accumulation is likely driven by inter‐ and intraspecific variability in plant traits, but the mechanisms that underpin this variability remain unresolved. In this study we evaluated how inter‐ and intraspecific variation in root traits of cultivars from switchgrass (Cave‐in‐Rock, Kanlow, Southlow) and big bluestem (Bonanza, Southlow, Suther) affected the associations of soil C accumulation across soil fractions using stable isotope techniques. Our experimental field site was established in June 2008 at Fermilab in Batavia, IL. In 2018, soil cores were collected (30 cm depth) from all cultivars. We measured root biomass, root diameter, specific root length, bulk soil C, C associated with coarse particulate organic matter (CPOM) and fine particulate organic matter plus silt‐ and clay‐sized fractions, and characterized organic matter chemical class composition in soil using high‐resolution Fourier‐transform ion cyclotron resonance mass spectrometry. C4 species were established on soils that supported C3 grassland for 36 years before planting, which allowed us to use differences in the natural abundance of stable C isotopes to quantify C4 plant‐derived C. We found that big bluestem had 36.9% higher C4 plant‐derived C compared to switchgrass in the CPOM fraction in the 0–10 cm depth, while switchgrass had 60.7% higher C4 plant‐derived C compared to big bluestem in the clay fraction in the 10–20 cm depth. Our findings suggest that the large root system in big bluestem helps increase POM‐C formation quickly, while switchgrass root structure and chemistry build a mineral‐bound clay C pool through time. Thus, both species and cultivar selection can help improve bioenergy management to maximize soil carbon gains and lower CO2 emissions.

BackgroundChronic pain and problematic substance use are commonly co-occurring and highly detrimental issues that are especially prevalent in U.S. veteran populations. Although COVID-19 made clinical management of these conditions potentially difficult, some research suggests that certain veterans with these conditions did not experience this period as negatively as others. It is thus important to consider whether resilience factors, such as the increasingly-studied process of psychological flexibility, might have led to better outcomes for veterans managing pain and problematic substance use during this time of global crisis.MethodsThis planned sub-analysis of a larger cross-sectional, anonymous, and nationally-distributed survey (N = 409) was collected during the first year of the COVID-19 pandemic. Veteran participants completed a short screener and battery of online surveys assessing pain severity and interference, substance use, psychological flexibility, mental health functioning, and pandemic-related quality of life.ResultsFor veterans with chronic pain and problematic substance use, the pandemic resulted in a significant lowering of their quality of life related to meeting basic needs, emotional health, and physical health compared to veterans with problematic substance use but no chronic pain diagnosis. However, moderation analyses revealed that veterans with these comorbid conditions experienced less negative impacts from the pandemic on quality of life and mental health when they reported greater psychological flexibility. For veterans with problematic substance use only, psychological flexibility was also related to better mental health functioning, but did not significantly correlate with their quality of life.ConclusionResults highlight how COVID-19 differentially impacted veterans with both problematic substance use and chronic pain, such that this group reported particularly negative impacts of the pandemic on multiple areas of quality of life. However, our findings further emphasize that psychological flexibility, a modifiable resiliency process, also buffered against some of the negative impacts of the pandemic on mental health and quality of life. Given this, future research into the impact of natural crises and healthcare management should investigate how psychological flexibility can be targeted to help increase resiliency for veterans with chronic pain and problematic substance use.

BackgroundDespite the declining prevalence of cigarette smoking in the United States, socioeconomically disadvantaged veterans receiving care from the Veterans Health Administration have a high prevalence of smoking. Currently, available treatment options for these veterans focus on tobacco users who are ready to quit and have limited reach. Consequently, there is a great need for accessible, effective smoking cessation interventions for veterans at all levels of readiness to quit smoking. ObjectiveTo address these needs, we developed Vet Flexiquit, a web-based Acceptance and Commitment Therapy program for veterans, and evaluated its acceptability (primary aim), efficacy, and impact on theory-based change processes relative to the National Cancer Institute’s SmokefreeVET program in a pilot randomized controlled trial. MethodsParticipants (N=49) were randomized 1:1 to receive either the Vet Flexiquit (n=25) or SmokefreeVET (n=24) web program. Both groups received SMS text messages as part of the intervention for 6 weeks. Both interventions are fully automated and self-guided. Primary outcome data were collected at 3 months after the randomization. Self-reported smoking abstinence was biochemically verified using saliva cotinine. Multivariable logistic regression, negative binomial regression, and linear regression models were used to evaluate the association between the treatment arm and outcomes of interest. ResultsAcceptability, as measured by overall treatment satisfaction, was high and similar across treatment arms: 100% (17/17) for Vet Flexiquit and 95% (18/19) for SmokefreeVET. Acceptability, as measured by utilization, was more modest (log-ins: M=3.7 for Vet Flexiquit and M=3.2 for SmokefreeVET). There were no statistically significant differences between treatment arms for any acceptability measures. Similarly, there were no statistically significant differences between treatment arms in the secondary outcomes of smoking cessation or change in Acceptance and Commitment Therapy’s theory-based processes. In open-ended survey responses, some veterans in both treatment arms expressed interest in having support from a professional or peer to enhance their experience, as well as an expanded SMS text messaging program. ConclusionsBoth programs had high ratings of acceptability, limited utilization, and a similar impact on cessation and cessation processes. Taken together with the qualitative data suggesting that additional support may enhance participants’ experience of both programs, these preliminary findings suggest that the programs may have similar outcomes among veterans who are looking for a digital cessation treatment option and that integrating provider or peer support and enhancing the SMS text messaging program holds promise as a means of boosting engagement and outcomes for both programs. Trial RegistrationClinicalTrials.gov NCT04502524; https://clinicaltrials.gov/ct2/show/NCT04502524

BackgroundIn the veteran community, chronic pain is particularly prevalent and often debilitating. Until recently, veterans with chronic pain were offered primarily pharmacological intervention options, which rarely suffice and can also have negative health consequences. To better address chronic pain in veterans, the Veterans Health Administration has invested in novel, nonpharmacological behavior interventions that target both pain management and chronic pain–related functional issues. One approach, acceptance and commitment therapy (ACT) for chronic pain, is supported by decades of efficacy evidence for improving pain outcomes; however, ACT can be difficult to obtain owing to issues such as a lack of trained therapists or veterans having difficulty committing to the time and resources needed for the full clinician-led ACT protocol. Given the strong ACT evidence base combined with access limitations, we set out to develop and evaluate Veteran ACT for Chronic Pain (VACT-CP), an online program guided by an embodied conversational agent to improve pain management and functioning. ObjectiveThe aims of this study are to develop, iteratively refine, and then conduct a pilot feasibility randomized controlled trial (RCT) of a VACT-CP group (n=20) versus a waitlist and treatment-as-usual control group (n=20). MethodsThis research project includes 3 phases. In phase 1, our research team consulted with pain and virtual care experts, developed the preliminary VACT-CP online program, and conducted interviews with providers to obtain their feedback on the intervention. In phase 2, we incorporated feedback from phase 1 into the VACT-CP program and completed initial usability testing with veterans with chronic pain. In phase 3, we are conducting a small pilot feasibility RCT, with the primary outcome being assessment of usability of the VACT-CP system. ResultsThis study is currently in phase 3; recruitment for the RCT began in April 2022 and is expected to continue through April 2023. Data collection is expected to be completed by October 2023, with full data analysis completed by late 2023. ConclusionsThe findings from this research project will provide information on the usability of the VACT-CP intervention, as well as secondary outcomes related to treatment satisfaction, pain outcomes (pain-related daily functioning and pain severity), ACT processes (pain acceptance, behavioral avoidance, and valued living), and mental and physical functioning. Trial RegistrationClinicalTrials.gov NCT03655132; https://clinicaltrials.gov/ct2/show/NCT03655132 International Registered Report Identifier (IRRID)DERR1-10.2196/45887

IntroductionThe COVID-19 pandemic generated concerns about rising stress and alcohol use, especially in U.S. veterans who experience high rates of anxiety disorders (ADs), alcohol use disorder (AUD), and dual AD+AUD diagnoses. This study investigated differences among these diagnostic groups in a veteran population related to their concern about COVID-19, impacts of COVID-19 on quality of life, and self-reported changes to urge to drink and drinking frequency.MethodsA nationally administered online survey was given to a sample of U.S. veterans reporting substance use issues during the pandemic. Differences in the level of concern about COVID-19, impacts of COVID-19 on quality of life, and drinking behaviors were examined in those self-reporting AD (n = 98), AUD (n = 46), or AD+AUD (n = 67). Consensual qualitative research was used to analyze an open-ended question about COVID-19’s impact on substance use, health, and quality of life.ResultsVeterans with AD+AUD experienced significant increases in urge to drink and alcohol consumption compared to veterans with AD only. Greater urge and frequency of drinking were associated with greater negative impacts of COVID-19 on quality of life. There were no differences among groups in global negative impact on quality of life or level of COVID-19 concern. However, respondents described specific COVID-19 worries, with qualitative findings revealing that those with AD+AUD reported a disproportionate psychosocial burden due to the pandemic.DiscussionSpecial attention in screening and treatment should be given to those with a dual AD+AUD diagnosis who may be experiencing both an increase in alcohol use and psychosocial burden as stress increases due to the pandemic.

BackgroundPeople with serious mental illness are disproportionately affected by smoking and face barriers to accessing smoking cessation treatments in mental health treatment settings. Text-based interventions are cost-effective and represent a widely accessible approach to providing smoking cessation support. ObjectiveWe aimed to identify key factors for adapting text-based cessation interventions for people with serious mental illness who smoke. MethodsWe recruited 24 adults from mental health programs who had a serious mental illness and currently smoked cigarettes or had quit smoking within the past 5 years. We then conducted virtual qualitative interviews between November 2020 and August 2021. Data were analyzed using the rapid thematic analytic approach. ResultsWe identified the following 3 major themes: (1) interplay between smoking and having a serious mental illness, (2) social contextual factors of smoking in adults with serious mental illness, and (3) smoking and quitting behaviors similar to the general population. Participants reported barriers and facilitators to quitting across the 3 themes. Within the “interplay between smoking and having a serious mental illness” theme, barriers included smoking to manage stress and mental health symptoms, and facilitators to quitting included the awareness of the harm of smoking on mental health and patient-provider discussions on smoking and mental health. In the “social contextual factors of smoking in adults with serious mental illness” theme, barriers included high social acceptability of smoking among peers. Positive support and the combined social stigma of smoking and having a mental health condition outside of peer groups motivated individuals to quit. Some participants indicated that low exposure to other smokers during the COVID-19 pandemic helped them to engage in cessation efforts. In the “smoking and quitting behaviors similar to the general population” theme, barriers included smoking after eating, having coffee, drinking alcohol, and experiencing negative social support, and facilitators included health concerns, improvement in the general quality of life, and use of evidence-based tobacco treatments when available. ConclusionsPeople with serious mental illness often smoke to cope with intense emotional states, manage mental health symptoms, or maintain social bonds. Text message content emphasizing equally effective and less harmful ways for stress reduction and mental health symptom management may improve quit rates in individuals with serious mental illness.

Age-related decrements in the central nervous system (CNS) are thought to result from: (1) increased susceptibility to and accumulating effects of free radicals and inflammation; and (2) dysregulation in Ca2+ homeostasis, which affects numerous signaling pathways. Certain bioactive phytochemicals exhibit potent anti-inflammatory activities which may mitigate these age-related CNS decrements. This study investigated the individual and combination effects of green tea catechin (epigallocatechin gallate, EGCG), curcumin from turmeric, and broccoli sprouts which contain the isothiocyanate sulforaphane on inflammation and dysregulation in Ca2+ homeostasis to determine if the individual compounds were working synergistically and/or through independent mechanisms. Rat hippocampal neurons or highly aggressive proliferating immortalized (HAPI) microglial cells were pre-treated for a week with either the individual components or all in combination before inducing Ca2+ buffering deficits with dopamine (DA, 0.1 µM for 2 h) or inflammation using lipopolysaccharide (LPS, 100 ng/mL for 18 h), respectively. The EGCG (3 µM) and combination protected against DA-induced deficits in Ca2+ buffering (both % of cells that recovered and recovery time, p < 0.05). Additionally, the EGCG and combination reduced stress-mediated inflammation in HAPI rat microglial cells by attenuating LPS-induced nitrite release, inducible nitrous oxide synthase (iNOS) expression, and tumor necrosis factor-alpha (TNF-α) release (p < 0.05), but not cyclooxygenase-2 (COX-2) expression. Overall, broccoli sprouts (2 µM) and curcumin (1 µM) were not as effective as the EGCG or combination. Further research is needed to determine if dietary intervention with a variety of foods containing compounds such as those found in green tea, turmeric, or broccoli sprouts can play a role in reducing age-related CNS inflammation, microglial activation, and downstream signaling pathways that can lead to neuronal dysfunction.

BackgroundSexual and gender minority young adults have a high prevalence of smoking and unique barriers to accessing tobacco treatment. ObjectiveTo address these challenges as well as their preferences for sexual and gender minority–targeted interventions and digital programs, we developed and evaluated the acceptability, preliminary efficacy, and impact on theory-based change processes of an acceptance and commitment therapy–based digital program called Empowered, Queer, Quitting, and Living (EQQUAL). MethodsParticipants (n=22) of a single-arm trial conducted to evaluate the program were young adults, age 18 to 30 years, who self-identified as sexual and gender minority individuals and smoked at least one cigarette per day. All participants received access to the EQQUAL program. Participants completed web-based surveys at baseline and at a follow-up 2 months after enrollment. We verified self-reported smoking abstinence with biochemical testing; missing data were counted as smoking or using tobacco. ResultsFor young adults who logged in at least once (n=18), the mean number of log-ins was 5.5 (SD 3.6), mean number of sessions completed was 3.1 (SD 2.6), and 39% (7/18) completed all 6 sessions. Overall, 93% of participants (14/15) were satisfied with the EQQUAL program, 100% (15/15) found it easy to use, and 100% (15/15) said it helped them be clearer about how to quit. Abstinence from smoking or using tobacco was confirmed with biochemical testing for 23% of participants (5/22). Both quantitative and qualitative results suggested a positive overall response to the avatar guide, with areas for future improvement largely centered on the avatar’s appearance and movements. ConclusionsTreatment acceptability of EQQUAL was very promising. The rate of abstinence, which was biochemically confirmed, was 3 times higher than that of the only other digital program to date that has targeted sexual and gender minority young adults and 6 to 13 times higher than those of nontargeted digital smoking interventions among sexual and gender minority young adults. Planned improvements for the next iteration of the program include making the avatar’s movements more natural; offering multiple avatar guides with different on characteristics such as race, ethnicity, and gender identity from which to choose; and providing a support forum for users to connect anonymously with peers.

Primary graft dysfunction (PGD) is the predominant cause of early graft loss following lung transplantation. We recently demonstrated that donor pulmonary intravascular nonclassical monocytes (NCM) initiate neutrophil recruitment. Simultaneously, host-origin classical monocytes (CM) permeabilize the vascular endothelium to allow neutrophil extravasation necessary for PGD. Here, we show that a CCL2-CCR2 axis is necessary for CM recruitment. Surprisingly, although intravital imaging and multichannel flow cytometry revealed that depletion of donor NCM abrogated CM recruitment, single cell RNA sequencing identified donor alveolar macrophages (AM) as predominant CCL2 secretors. Unbiased transcriptomic analysis of murine tissues combined with murine KOs and chimeras indicated that IL-1β production by donor NCM was responsible for the early activation of AM and CCL2 release. IL-1β production by NCM was NLRP3 inflammasome dependent and inhibited by treatment with a clinically approved sulphonylurea. Production of CCL2 in the donor AM occurred through IL-1R–dependent activation of the PKC and NF-κB pathway. Accordingly, we show that IL-1β–dependent paracrine interaction between donor NCM and AM leads to recruitment of recipient CM necessary for PGD. Since depletion of donor NCM, IL-1β, or IL-1R antagonism and inflammasome inhibition abrogated recruitment of CM and PGD and are feasible using FDA-approved compounds, our findings may have potential for clinical translation.

Summary: Low-abundance short-lived non-native conformations referred to as excited states (ESs) are increasingly observed in vitro and implicated in the folding and biological activities of regulatory RNAs. We developed an approach for assessing the relative abundance of RNA ESs within the functional cellular context. Nuclear magnetic resonance (NMR) spectroscopy was used to estimate the degree to which substitution mutations bias conformational equilibria toward the inactive ES in vitro. The cellular activity of the ES-stabilizing mutants was used as an indirect measure of the conformational equilibria within the functional cellular context. Compensatory mutations that restore the ground-state conformation were used to control for changes in sequence. Using this approach, we show that the ESs of two regulatory RNAs from HIV-1, the transactivation response element (TAR) and the Rev response element (RRE), likely form in cells with abundances comparable to those measured in vitro, and their targeted stabilization may provide an avenue for developing anti-HIV therapeutics. : Ganser et al. use point mutations to bias conformational equilibria in HIV-1 TAR and RRE RNA toward inactive excited states. Comparing the conformational bias induced in vitro with biological activity measured in cells suggests similar structural dynamics in vitro and in cells for these two RNAs. Keywords: HIV-1 transactivation response element, TAR, Rev response element, RRE, RNA dynamics, RNA drug discovery, transactivation, excited state, RNA structure, structure mapping, cellular activity, conformational switches

Abstract Background Prevalence estimates internationally suggest that many preschool-aged children (3–5 years) are insufficiently physically active and engage in high levels of screen-based entertainment. Early childhood is the developmental period for which we know the least about the effects of physical activity on development and health. Likewise, rapid technological advancements in mobile electronic media have made screen-based forms of entertainment for young children ubiquitous, and research demonstrating the impacts on cognition, psychosocial well-being, and health has lagged behind the rate of adoption of these technologies. The purpose of the Preschool Activity, Technology, Health, Adiposity, Behaviour and Cognition (PATH-ABC) study is to investigate if physical activity and screen-based entertainment are independently associated with cognitive and psychosocial development, and health outcomes in young children, and if so, how much and which types of these behaviours might be most influential. Methods The PATH-ABC study is a prospective cohort, aiming to recruit 430 3–5 year-old children. Children are recruited through and complete initial assessments at their Early Childhood Education and Care (ECEC) centre, and then 12-months later at their centre or school. Direct assessments are made of children’s habitual physical activity using accelerometry, cognitive (executive function) and language development (expressive vocabulary), psychosocial development (emotional understanding, Theory of Mind, empathy, and heart rate variability), adiposity (body mass index and waist circumference), and cardiovascular health (blood pressure and retinal micro- vasculature). Educators report on children’s psychological strengths and difficulties and self-regulation. Parents report on children’s habitual use of electronic media and other child, parent and household characteristics. Discussion The PATH-ABC study aims to provide evidence to enhance understanding of how much and which types of physical activity and screen-based media influence development and health in preschool-aged children. This information would benefit parents, educators, health professionals and governments seeking to develop strategies and policies to give young children the best start in life by promoting healthy levels of physical activity and electronic media use.

Tart cherries contain an array of polyphenols that can decrease inflammation and oxidative stress (OS), which contribute to cognitive declines seen in aging populations. Previous studies have shown that polyphenols from dark-colored fruits can reduce stress-mediated signaling in BV-2 mouse microglial cells, leading to decreases in nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression. Thus, the present study sought to determine if tart cherries—which improved cognitive behavior in aged rats—would be efficacious in reducing inflammatory and OS signaling in HAPI rat microglial cells. Cells were pretreated with different concentrations (0–1.0 mg/mL) of Montmorency tart cherry powder for 1–4 h, then treated with 0 or 100 ng/mL lipopolysaccharide (LPS) overnight. LPS application increased extracellular levels of NO and tumor necrosis factor-alpha (TNF-α), and intracellular levels of iNOS and cyclooxygenase-2 (COX-2). Pretreatment with tart cherry decreased levels of NO, TNF-α, and COX-2 in a dose- and time-dependent manner versus those without pretreatment; the optimal combination was between 0.125 and 0.25 mg/mL tart cherry for 2 h. Higher concentrations of tart cherry powder and longer exposure times negatively affected cell viability. Therefore, tart cherries (like other dark-colored fruits), may be effective in reducing inflammatory and OS-mediated signals.