Early-life risperidone alters locomotor responses to apomorphine and quinpirole in adulthood.

An escalating trend of antipsychotic drug use in children with ADHD, disruptive behavior disorder, or mood disorders has raised concerns about the impact of these drugs on brain development. Since antipsychotics chiefly target dopamine receptors, it is important to assay the function of these receptors after early-life antipsychotic administration. Using rats as a model, we examined the effects of early-life risperidone, the most prescribed antipsychotic drug in children, on locomotor responses to the dopamine D1/D2 receptor agonist, apomorphine, and the D2/D3 receptor agonist, quinpirole. Female and male Long-Evans rats received daily subcutaneous injections of risperidone (1.0 and 3.0 mg/kg) or vehicle from postnatal day 14-42. Locomotor responses to one of three doses (0.03, 0.1, and 0.3 mg/kg) of apomorphine or quinpirole were tested once a week for four weeks beginning on postnatal day 76 and 147 for each respective drug. The locomotor activity elicited by the two lower doses of apomorphine was significantly greater in adult rats, especially females, administered risperidone early in life. Adult rats administered risperidone early in life also showed more locomotor activity after the low dose of quinpirole. Overall, female rats were more sensitive to the locomotor effects of each agonist. In a separate group of rats administered risperidone early in life, autoradiography of forebrain D2 receptors at postnatal day 62 revealed a modest increase in D2 receptor density in the medial caudate. These results provide evidence that early-life risperidone administration can produce long-lasting changes in dopamine receptor function and density.

Development of a clinical and translational research curriculum for undergraduate students.

Introduction: Research participation during undergraduate years has a powerful influence on career selection and attitudes toward scientific research. Most undergraduate research programs in academic health centers are oriented toward basic research or address a particular disease focus or research discipline. Undergraduate research programs that expose students to clinical and translational research may alter student perceptions about research and influence career selection. Methods: We developed an undergraduate summer research curriculum, anchored upon a clinical and translational research study developed to address a common unmet needs in neonatal nurseries (e.g., assessment of neonatal opioid withdrawal syndrome). Program topics reflected the cross-disciplinary expertise that contributed to the development of this "bedside to bench" study, including opioid addiction, vulnerable populations, research ethics, statistics, data collection and management, assay development, analytical laboratory analysis, and pharmacokinetics. The curriculum was delivered through three offerings over 12 months, using Zoom video-conferencing due to restrictions imposed by the COVID-19 pandemic. Results: Nine students participated in the program. Two-thirds reported the course enhanced their understanding of clinical and translational research. Over three-quarters reported the curriculum topics were very good or excellent. In open-ended questions, students reported that the cross-disciplinary nature of the curriculum was the strongest aspect of the program. Conclusion: The curriculum could be readily adapted by other Clinical and Translational Science Award programs seeking to provide clinical and translational research-oriented programs to undergraduate students. Application of cross-disciplinary research approaches to a specific clinical and translational research question provides students with relevant examples of translational research and translational science.

An integrated approach to address diabetes in the context of food insecurity: Delivering health study protocol.

Background: Diabetes self-management education and support (DSMES) interventions among food insecure individuals with type 2 diabetes (T2D) have found modest improvements in nutrition and health outcomes but are limited by barriers to attendance and retention. This study applies a community-based participatory research approach, engaging community members at all levels of intervention planning, development, implementation, and dissemination, to deliver a plain-language DSMES curriculum to food insecure community members with T2D. Methods: This is a single-arm, pre-post design assessing the efficacy of a 12-week home-delivered DSMES curriculum and T2D-appropriate food box intervention to improve the nutrition and health outcomes of food insecure individuals with T2D. The intervention consists of a weekly food box delivery and handout with video links on key DSMES topics, developed and refined using community advisor feedback. Up to 100 English-, Spanish-, or Marshallese-speaking adult participants with T2D (HbA1c ≥ 7%) and food insecurity are being recruited from food pantries in northwest Arkansas. Data is collected at pre-intervention and immediately post-intervention. The primary study outcome is change in HbA1c. Secondary measures include diet quality (Healthy Eating Index-2015, calculated from 3 24-h dietary recall interviews via phone), body mass index, blood pressure, skin carotenoids, food security, T2D self-management behaviors, T2D self-efficacy, and T2D-related distress. Results: Recruitment began in August 2021 and enrollment is anticipated to be complete in March 2023. Conclusion: Findings from this study will provide a rich understanding of diabetes-related health outcomes and dietary patterns of individuals with food insecurity and T2D and inform future food-focused DSMES interventions in this setting.

Prevalence and associations between food insecurity and overweight/obesity among native Hawaiian and Pacific Islander adolescents.

OBJECTIVE: This study estimates the prevalence of, and associations between, family food insecurity and overweight/obesity among Native Hawaiian and Pacific Islander (NHPI) adolescents and explores socio-demographic factors which might have a moderation effect on the association. DESIGN: Cross-sectional study using 2014 NHPI-National Health Interview Survey data reported by a parent or guardian. Family-level food security was assessed by the US Department of Agriculture 10-item questionnaire. BMI for age and sex ≥ 85th and 95th percentiles defined overweight and obesity, respectively, according to US Centers for Disease Control and Prevention criteria. SETTING: The USA, including all 50 states and the District of Columbia. PARTICIPANTS: 383 NHPI adolescents aged 12-17 in the USA. RESULTS: A third (33·5 %) of NHPI adolescents aged 12-17 were overweight (19·1 %) or obese (14·4 %); 8·1 % had low food security; and 8·5 % had very low food security. Mean family food security score was 1·06, which corresponds to marginal food security. We found no association between family food insecurity and adolescent overweight/obesity or between any other covariates and overweight/obesity, except for family Supplemental Nutrition Assistance Program (SNAP) participation. Odds of being overweight/obese were 77 % lower for adolescents in families participating in SNAP (OR: 0·23, 95 % CI: 0·08, 0·64, P = 0·007). The association between SNAP participation and lower odds of overweight/obesity was particularly pronounced for adolescent girls in food-insecure families. CONCLUSIONS: The association between SNAP participation and lower odds of overweight/obesity suggests potential benefit of research to determine whether interventions to increase SNAP enrollment would improve NHPI adolescents' health outcomes.

Practice facilitation for scale up of clinical decision support for hypertension management: study protocol for a cluster randomized control trial.

BACKGROUND: Only half of patients with hypertension have adequately controlled blood pressure. Clinical decision support (CDS) has the potential to overcome barriers to delivering guideline-recommended care and improve hypertension management. However, optimal strategies for scaling CDS have not been well established, particularly in small, independent primary care practices which often lack the resources to effectively change practice routines. Practice facilitation is an implementation strategy that has been shown to support process changes. Our objective is to evaluate whether practice facilitation provided with hypertension-focused CDS can lead to improvements in blood pressure control for patients seen in small primary care practices. METHODS/DESIGN: We will conduct a cluster randomized control trial to compare the effect of hypertension-focused CDS plus practice facilitation on BP control, as compared to CDS alone. The practice facilitation intervention will include an initial training in the CDS and a review of current guidelines along with follow-up for coaching and integration support. We will randomize 46 small primary care practices in New York City who use the same electronic health record vendor to intervention or control. All patients with hypertension seen at these practices will be included in the evaluation. We will also assess implementation of CDS in all practices and practice facilitation in the intervention group. DISCUSSION: The results of this study will inform optimal implementation of CDS into small primary care practices, where much of care delivery occurs in the U.S. Additionally, our assessment of barriers and facilitators to implementation will support future scaling of the intervention. CLINICALTRIALS: gov Identifier: NCT05588466.

Experiences of Farmers Market Vendors in a Healthy Food Incentive Program.

Healthy food incentive programs for Supplemental Nutrition Assistance Program participants, often implemented in farmers markets, have shown promise in improving the purchase and consumption of fruits and vegetables. However, variation in program context, program strategies, and participant populations has produced gaps in knowledge about which healthy food incentive program implementation strategies are most effective, and few studies have focused on farmers market vendors' experiences. This study evaluated experiences of farmers market vendors who participated in the Northwest Arkansas Double Your Dollars (NWA DYD) healthy food incentive program intended to increase access to healthy foods for local Hispanic/Latino and Marshallese community members with low incomes. Data were collected from a convenience sample of vendors participating in NWA DYD at the three largest participating markets on the last Saturday in October 2021. Program staff collected quantitative, categorical, and open-ended data through face-to-face surveys. Forty-one vendors completed the survey. Vendors believed NWA DYD was beneficial and easy to use, expanded their customer base, and increased participation of Hispanic/Latino and Marshallese shoppers. Vendors also identified challenges in participation related to administrative burdens and delayed reimbursements. Vendors did not identify NWA DYD as a driver for expanded production for the upcoming growing season. Vendors' experiences at NWA DYD provide implications for others interested in implementing effective healthy food incentive programs. Improving access to farmers markets through effective healthy food incentive programs is an important step toward increasing consumption of fresh, healthy foods among communities with low incomes facing elevated prevalence of chronic disease.

Implementation and Preliminary Effectiveness of a Multidisciplinary Telemedicine Pilot Initiative for Patients with Chronic Non-Cancer Pain in Rural and Underserved Areas at a Major Academic Medical Center.

Background: Arkansas lacks adequate access to high-quality pain care, as evidenced, in part, by it having the second highest opioid prescribing rate in the United States. To improve access to high-quality treatment of chronic pain, we developed the Arkansas Improving Multidisciplinary Pain Care and Treatment (AR-IMPACT) Telemedicine Clinic, a multidisciplinary and interprofessional team of specialists who provide evidence-based pain management for patients with chronic pain. Methods: We conducted a single-arm pilot trial of the AR-IMPACT Telemedicine Clinic with rural, university-affiliated primary care clinics. We assessed the AR-IMPACT Telemedicine Clinic using an implementation framework and preliminary effectiveness measures. Specifically, we assessed 5 of the 8 implementation outcomes of the framework (ie, penetration, adoption, acceptability, appropriateness, and feasibility) using a mixed methods approach. To evaluate implementation outcomes, we used surveys, interviews, and administrative data. We used electronic health record data to measure preliminary effectiveness (ie, changes in average morphine milligram equivalents per day and pain and depression scores). Results: The AR-IMPACT team saw 23 patients that were referred by 13 primary care physicians from three rural, university-affiliated primary care clinics over one year. Of the 19 patients willing to participate in the pilot study, 12 identified as women, 31.6% identified as Black, and over 50% had less than a bachelor's level education. Patients rated the clinic positively with high overall satisfaction. Referring physicians indicated high levels of appropriateness, acceptability, and feasibility of the program. AR-IMPACT team members identified several barriers and facilitators to the feasibility of implementing the program. No changes in preliminary effectiveness measures were statistically significant. Conclusion: Overall, the AR-IMPACT Telemedicine Clinic obtained moderate penetration and adoption, was highly acceptable to patients, was highly acceptable and appropriate to providers, and was moderately feasible to providers and AR-IMPACT team members.

Reducing Sodium Content of Foods Served in Arkansas's Largest School District: Evaluation of the Sodium Reduction in Communities Program.

PURPOSE AND OBJECTIVES: The Centers for Disease Control and Prevention's Sodium Reduction in Communities Program aims to reduce dietary sodium intake through policy, systems, and environmental approaches. The objective of our study was to evaluate changes in sodium levels over 5 years (2016-2021) in food served in school lunches as an outcome of a Sodium Reduction in Communities program in Arkansas's largest school district. INTERVENTION APPROACH: We collaborated with Springdale Public Schools (SPS) to reduce dietary sodium intake in school lunches through increased implementation of 1) food service guidelines, 2) procurement practices, 3) food preparation practices, and 4) environmental strategies. These activities were maintained from year 1 through year 5. Implementation priorities were informed each year by evaluation findings from the preceding year. EVALUATION METHODS: We collected lunch service records and information on nutritional content of menu items for the 30 schools under the direction of SPS's Child Nutrition Department. We used a pretest-posttest quantitative evaluation design to analyze annual changes in the sodium content of meals, from baseline through year 5. RESULTS: From baseline through year 1, SPS reduced sodium served per diner, per entrée offered, and per entrée served. These reductions were maintained from baseline through 5 years of follow-up. Mean sodium per 1,000 kcal per diner served was 1,740 mg at baseline and was lower in each of the 5 follow-up years: 1,488 mg (14% decrease) in year 1; 1,495 mg (14% decrease) in year 2; 1,612 mg (7% decrease) in year 3; 1,560 mg (10% decrease) in year 4; and 1,532 mg (12% decrease) in year 5. Energy served per diner remained stable. IMPLICATIONS FOR PUBLIC HEALTH: Our study provides evidence for sustained sodium reduction strategies in a large ethnically and socioeconomically diverse school district, pointing to the potential benefit of implementing similar strategies in other school districts. The study also shows how program evaluation can be used to support sustainability.

Homeostatic plasticity in human extrastriate cortex following a simulated peripheral scotoma.

Neuroimaging and patient work over the past decade have indicated that, following retinal deafferentation, the human visual cortex undergoes a large-scale and enduring reorganization of its topography such that the classical retinotopic organization of deafferented visual cortex remaps to represent non-classical regions of visual space. Such long-term visual reorganization is proposed to occur through changes in the functional balance of deafferented visual circuits that engage more lasting changes through activity-dependent neuroplasticity. Here, we investigated the short-term changes in functional balance (short-term plasticity; homeostatic plasticity) that occur within deafferented human visual cortices. We recorded electroencephalogram (EEG) while observers were conditioned for 6 s with a simulated retinal scotoma (artificial scotoma) positioned 8.0° in the periphery. Visual evoked potentials (VEPs) evoked by the onset of sinusoidal visual probes that varied in their tilt were used to examine changes in cortical excitability within and around cortical representations of the simulated scotoma. Psychophysical orientation functions obtained from discrimination of visual probe tilt were used to examine alterations in the stimulus selectivity within the scotoma representations. Consistent with a mechanism of homeostatic disinhibition, an early extrastriate component of the VEP (the early phase P1) exhibited increased amplitude following the condition with a simulated scotoma relative to a stimulus-matched control condition. This increased visual cortical response was associated with a reduction in the slope of the psychophysical orientation function, suggesting a broader tuning of neural populations within scotoma representations. Together, these findings support a mechanism of disinhibition in promoting visual plasticity and topographical reorganization.

Spatial Scaling of the Profile of Selective Attention in the Visual Field.

Neural mechanisms of selective attention must be capable of adapting to variation in the absolute size of an attended stimulus in the ever-changing visual environment. To date, little is known regarding how attentional selection interacts with fluctuations in the spatial expanse of an attended object. Here, we use event-related potentials (ERPs) to investigate the scaling of attentional enhancement and suppression across the visual field. We measured ERPs while participants performed a task at fixation that varied in its attentional demands (attentional load) and visual angle (1.0° or 2.5°). Observers were presented with a stream of task-relevant stimuli while foveal, parafoveal, and peripheral visual locations were probed by irrelevant distractor stimuli. We found two important effects in the N1 component of visual ERPs. First, N1 modulations to task-relevant stimuli indexed attentional selection of stimuli during the load task and further correlated with task performance. Second, with increased task size, attentional modulation of the N1 to distractor stimuli showed a differential pattern that was consistent with a scaling of attentional selection. Together, these results demonstrate that the size of an attended stimulus scales the profile of attentional selection across the visual field and provides insights into the attentional mechanisms associated with such spatial scaling.

Delayed yet persistent effects of daily risperidone on activity in developing rats.

Early-life administration of risperidone, the most widely used antipsychotic drug in children, leads to persistently elevated locomotor activity in adult rats. This study determined whether and when elevated locomotor activity emerges during developmental risperidone administration. Developing and adult rats were administered daily injections of risperidone (1.0 and 3.0 mg/kg) or vehicle for 4 weeks beginning at postnatal days 14 and 74, respectively. Starting with the first injection and every 7 days thereafter, locomotor activity was measured immediately after the injection and 20 min before the next day's injection. Activity was also recorded 1 week after the final injection. Risperidone markedly decreased locomotor activity in developing and adult rats immediately after injection. Within 24 h after their first injection, adult rats administered risperidone showed greater activity levels. In contrast, developing rats did not show compensatory hyperactivity until the beginning of the fourth week of risperidone administration. One week after the final risperidone injection, there was no evidence of hyperactivity in the adult rats maintained on risperidone, but developing rats administered risperidone, especially females, showed greater activity levels relative to vehicle-administered controls. In comparison with adult rats, the emergence of compensatory hyperactivity during long-term antipsychotic drug administration is delayed in developing rats, but persists after treatment cessation.

Bootstrap Signal-to-Noise Confidence Intervals: An Objective Method for Subject Exclusion and Quality Control in ERP Studies.

Analysis of event-related potential (ERP) data includes several steps to ensure that ERPs meet an appropriate level of signal quality. One such step, subject exclusion, rejects subject data if ERP waveforms fail to meet an appropriate level of signal quality. Subject exclusion is an important quality control step in the ERP analysis pipeline as it ensures that statistical inference is based only upon those subjects exhibiting clear evoked brain responses. This critical quality control step is most often performed simply through visual inspection of subject-level ERPs by investigators. Such an approach is qualitative, subjective, and susceptible to investigator bias, as there are no standards as to what constitutes an ERP of sufficient signal quality. Here, we describe a standardized and objective method for quantifying waveform quality in individual subjects and establishing criteria for subject exclusion. The approach uses bootstrap resampling of ERP waveforms (from a pool of all available trials) to compute a signal-to-noise ratio confidence interval (SNR-CI) for individual subject waveforms. The lower bound of this SNR-CI (SNRLB ) yields an effective and objective measure of signal quality as it ensures that ERP waveforms statistically exceed a desired signal-to-noise criterion. SNRLB provides a quantifiable metric of individual subject ERP quality and eliminates the need for subjective evaluation of waveform quality by the investigator. We detail the SNR-CI methodology, establish the efficacy of employing this approach with Monte Carlo simulations, and demonstrate its utility in practice when applied to ERP datasets.

Early-life risperidone administration alters maternal-offspring interactions and juvenile play fighting.

Risperidone is an antipsychotic drug that is approved for use in childhood psychiatric disorders such as autism. One concern regarding the use of this drug in pediatric populations is that it may interfere with social interactions that serve to nurture brain development. This study used rats to assess the impact of risperidone administration on maternal-offspring interactions and juvenile play fighting between cage mates. Mixed-sex litters received daily subcutaneous injections of vehicle or 1.0 or 3.0mg/kg of risperidone between postnatal days (PNDs) 14-42. Rats were weaned and housed three per cage on PND 21. In observations made between PNDs 14-17, risperidone significantly suppressed several aspects of maternal-offspring interactions at 1-hour post-injection. At 23 h post-injection, pups administered risperidone had lower activity scores and made fewer non-nursing contacts with their moms. In observations of play-fighting behavior made once a week between PNDs 22-42, risperidone profoundly decreased many forms of social interaction at 1h post-injection. At 23h post-injection, rats administered risperidone made more non-social contacts with their cage mates, but engaged in less social grooming. Risperidone administration to rats at ages analogous to early childhood through adolescence in humans produces a pattern of abnormal social interactions across the day that could impact how such interactions influence brain development.

Low levels of high-density lipoproteins are associated with acute kidney injury following revascularization for chronic limb ischemia.

OBJECTIVES: Perioperative acute kidney injury (AKI) is not uncommon, following revascularization. HDL has been shown to reduce organ injury in animal models. The aim of the study is to examine the association of HDL on AKI in patients undergoing revascularization for chronic limb ischemia. METHODS: All patients who underwent revascularization between June 2001 and December 2009 were analyzed. Patients on dialysis and with incomplete data were excluded. Patients were grouped for HDL < or ≥40 mg/dL. Univariate and multivariate analysis were used to identify factors associated with AKI. RESULTS: A total of 684 patients were included. Eighty-two (12.0%) patients developed postoperative AKI (15.7% in low HDL group vs. 6.3% in high HDL group, p < 0.001). The AKI group were more likely to be older (71.5 ± 10.1 vs. 68.0 ± 10.8, p = 0.01), ASA 4 class (26% vs. 14%, p < 0.001), to have albumin <3 g/dL (59% vs. 32%, p < 0.001), low HDL levels (79% vs. 58%, p < 0.001), DM (61% vs. 44%, p = 0.005), CAD (67% vs. 55%, p = 0.003), preoperative chronic kidney disease (CKD) stage III-IV (55% vs.39%, p < 0.001), to present with critical limb ischemia (82% vs. 63%, p = 0.001), and to be on ACEI (67% vs. 51%, p = 0.006). Multivariate logistic regression analysis showed low HDL (Odds Ratio (OR) 1.66 [1.23-2.24]) and serum albumin levels <3 g/dL (OR 1.66 [1.29-2.13], p < 0.001) were independently associated with increased odds for developing AKI. Propensity score analyses showed low HDL was independently associated with increased odds of AKI (OR 2.4 (1.4-4.2)). CONCLUSIONS: AKI following revascularization is not uncommon (12.0%), and lower concentrations of HDL and serum albumin are associated with increased odds of postoperative AKI. There was also a trend of higher prevalence of AKI among those with pre-existing CKD.