Search

BackgroundSex differences in immune-based disorders are well-established, with female sex associated with a markedly heightened risk of autoimmune disease. Female sex is also overrepresented in other conditions associated with elevated inflammation, including depression, chronic pain, and chronic fatigue. The mechanisms underlying these disparities are unclear. This study used an experimental model of inflammatory challenge to interrogate molecular mechanisms that may contribute to female vulnerability to disorders with an inflammatory basis.MethodIn this analysis of a secondary outcome from a randomized controlled trial, 111 participants (67 female) received either a bolus injection of endotoxin (n = 59) or placebo (n = 52). Participants provided blood samples before and 0.5 h post-injection for assessment of differential activation of key pro-inflammatory (i.e., activator protein (AP)-1; nuclear factor (NF)-κB) and immunoregulatory (i.e., glucocorticoid receptor (GR); cAMP response element binding protein (CREB)) signaling pathways via genome-wide expression profiling and promoter-based bioinformatics analyses.ResultsRelative to males, females exhibited greater endotoxin-induced increases in bioinformatic measures of CREB transcription factor activity (p's

BACKGROUND: Guided by the reserve capacity model, we evaluated the unique relationships between socioeconomic status (SES), reserve capacity (helplessness, self-efficacy, social support), and negative emotions on pain in patients with Rheumatoid Arthritis (RA). METHODS: The secondary analysis used baseline, cross-sectional data from 106 adults in a clinical trial comparing behavioral treatments for RA. Patients were eligible if they were ≥ 18 years old, met the ACR criteria for RA (determined by study rheumatologist), had stable disease and drug regimens for 3 months, and did not have a significant comorbid condition. Structural equation modeling evaluated the direct effects of SES, reserve capacity (helplessness- Arthritis Helplessness Index, self-efficacy -Personal Mastery Scale, social support- Social Provisions Scale) and negative emotions (stress and depressive symptoms- Perceived Stress Scale and Hamilton Depression Rating Scale) on pain (Rapid Assessment of Disease Activity in Rheumatology-RADAR & visual analog scale-VAS), and the indirect effects of SES as mediated by reserve capacity and negative emotions. The SEM model was evaluated using multiple fit criteria: χ2 goodness-of-fit statistic, the comparative fit index (CFI), the standardized root mean square residual (SRMR), and the root mean square error of approximation (RMSEA). RESULTS: Participants were mostly female (85%), 55.45 years old on average, self-identified as white (61%), Hispanic (16%), black (13%), and other (10%), and had RA for an average of 10.63 years. Results showed that low SES contributed to worse pain, through lower reserve capacity and higher negative emotions. Mediational analyses showed that reserve capacity and negative emotions partially mediated the effect of SES on pain. The final model explained 39% of the variance in pain. CONCLUSIONS: The findings indicate that lower SES was related to worse clinical pain outcomes and negative emotions and reserve capacity (helplessness, social support, and self-efficacy) mediated the effect of SES on pain. A primary limitation is the small sample size; future studies should evaluate this model further in larger, longitudinal approaches. Interventions that target negative emotions in patients with low SES may facilitate better pain control with RA. TRIAL REGISTRATION: clinicaltrials.gov NCT00072657 01/02/2004 20/03/2009.

The authors--a panel of teacher educators: an education librarian, and a high school student activist--share classroom practices, recent research, and scholarship that centers on fostering empathy and activism through picture books as part of culturally relevant-sustaining practices. A variety of new children's literature and practical ways to incorporate these inclusive picture books across the curriculum are shared. Useful strategies for teachers to locate culturally responsive & sustaining children's literature and related resources for classroom use are also provided.

Purpose: In this study, we examined the utility of vowel intelligibility testing for assessing the impact of dysarthria on speech characteristics in people with amyotrophic lateral sclerosis (ALS). We tested the sensitivity and specificity of overall vowel identification, as well as that of vowel-specific identification, to dysarthria presence and severity. We additionally examined the relationship between vowel intelligibility and sentence intelligibility. Method: Twenty-three people with ALS and 22 age- and sex-matched control speakers produced sentences from the Speech Intelligibility Test (SIT), as well as 10 American English monophthongs in /h/--vowel--/d/ words for the vowel intelligibility test (VIT). Data for SIT and VIT scores came from 135 listeners. Diagnostic accuracy of VIT measures was evaluated using the area under the curve of receiver operator characteristics. We then examined differences between control speakers, speakers with mild dysarthria, and speakers with severe dysarthria in their relationship between SIT and VIT scores. Results: The results suggest that the overall vowel intelligibility score showed high sensitivity and specificity in differentiating between speakers with and without dysarthria, even those with milder symptoms. In addition, single-vowel identification scores showed at least acceptable group differentiation between the mild and severe dysarthria groups, though fewer single vowels were acceptable discriminators between the control group and the group with mild dysarthria. Identification accuracy of /I/ in particular showed excellent discrimination across all groups. Examination of the relationship between SIT and VIT scores suggests a severity-specific relationship. Speakers with SIT scores above 70% generally had higher SIT than VIT scores, whereas speakers with SIT below 70% generally had higher VIT than SIT scores. Discussion: Vowel intelligibility testing can detect speech impairments in speakers with mild dysarthria and residual articulatory function in speakers with severe dysarthria. Vowel intelligibility testing may, therefore, be a useful addition to intelligibility testing for individuals with dysarthria.

Spinal cord circuits play crucial roles in transmitting pain, but the underlying activity patterns within and across spinal segments in behaving mice have remained elusive. We developed a wearable widefield macroscope with a 7.9-mm2 field of view, ~3- to 4-μm lateral resolution, 2.7-mm working distance and

Abstract Background Guided by the reserve capacity model, we evaluated the unique relationships between socioeconomic status (SES), reserve capacity (helplessness, self-efficacy, social support), and negative emotions on pain in patients with Rheumatoid Arthritis (RA). Methods The secondary analysis used baseline, cross-sectional data from 106 adults in a clinical trial comparing behavioral treatments for RA. Patients were eligible if they were ≥ 18 years old, met the ACR criteria for RA (determined by study rheumatologist), had stable disease and drug regimens for 3 months, and did not have a significant comorbid condition. Structural equation modeling evaluated the direct effects of SES, reserve capacity (helplessness- Arthritis Helplessness Index, self-efficacy -Personal Mastery Scale, social support- Social Provisions Scale) and negative emotions (stress and depressive symptoms- Perceived Stress Scale and Hamilton Depression Rating Scale) on pain (Rapid Assessment of Disease Activity in Rheumatology-RADAR & visual analog scale-VAS), and the indirect effects of SES as mediated by reserve capacity and negative emotions. The SEM model was evaluated using multiple fit criteria: χ2 goodness-of-fit statistic, the comparative fit index (CFI), the standardized root mean square residual (SRMR), and the root mean square error of approximation (RMSEA). Results Participants were mostly female (85%), 55.45 years old on average, self-identified as white (61%), Hispanic (16%), black (13%), and other (10%), and had RA for an average of 10.63 years. Results showed that low SES contributed to worse pain, through lower reserve capacity and higher negative emotions. Mediational analyses showed that reserve capacity and negative emotions partially mediated the effect of SES on pain. The final model explained 39% of the variance in pain. Conclusions The findings indicate that lower SES was related to worse clinical pain outcomes and negative emotions and reserve capacity (helplessness, social support, and self-efficacy) mediated the effect of SES on pain. A primary limitation is the small sample size; future studies should evaluate this model further in larger, longitudinal approaches. Interventions that target negative emotions in patients with low SES may facilitate better pain control with RA. Trial registration clinicaltrials.gov NCT00072657 01/02/2004 20/03/2009.

Little is known about how emerging adults respond emotionally to pornography use. Using a two-study approach, we first examined emerging adults' (N = 269) positive and negative emotional reactions to their own pornography use. Study 2 (N = 517) extended these findings by (a) examining how these emotional reactions are related to well-being and (b) exploring the various ways pornography use can interfere with life. Mixed findings from these two studies demonstrate both positive and negative outcomes for emerging adult men and women. The differential emotional experiences of pornography use and its effects on emerging adults' lives merit further investigation.

STUDY OBJECTIVES: Disturbances of sleep maintenance and sleep duration are common in older adults and associated with an increased risk for age-related mortality and morbidity. Converging evidence implicates inflammation as an underlying mechanism, especially in females. However, it is unknown what specific aspects of sleep disturbance impact inflammatory mechanisms in older adults. METHODS: Using data from community-dwelling older adults who participated in the Sleep Health and Aging Research (SHARE) field study (n = 262, mean age 71.9 ± 8.0 years), we conducted a secondary analysis to examine whether disturbance of sleep maintenance (i.e. greater amount of wake time after sleep onset [WASO]) and sleep duration (i.e. shorter total sleep time [TST]) assessed by sleep diary and actigraphy are associated with greater activation of nuclear factor (NF)-κB and signal transducer and activator of transcription (STAT) family proteins STAT1, STAT3, and STAT5 in peripheral blood monocytic cells. In addition, moderation effects of sex were explored. RESULTS: Data were available for sleep diary (n = 82), actigraphy (n = 74), and inflammatory signaling and transcriptional measures (n = 132). As assessed by sleep diary, greater amount of WASO (β = 0.39, p < 0.01), but not TST, was associated with higher levels of NF-κB. Whereas diary-assessed sleep measures were not associated with STAT family proteins, a moderation analysis revealed that greater diary-assessed WASO was associated with higher levels of STAT1 (p < 0.05), STAT3 (p < 0.05), and STAT5 (p < 0.01) in females, but not in males. Actigraphy-assessed sleep measures were not associated either with NF-κB or STAT activation. CONCLUSIONS: In older adults, self-reported disturbance of sleep maintenance assessed by sleep diary was uniquely associated with higher levels of NF-κB, along with higher levels of STAT family proteins in females, but not in males. Our data suggest that improvingself-reported sleep maintenance might mitigate age-related increases in inflammatory signaling and transcriptional pathways, possibly more strongly in females, with the potential to reduce mortality risk in older adults.

BACKGROUND: Inflammation has been associated with alcohol use disorder (AUD). A novel method to characterize AUD-related immune signaling involves probing Toll-like receptor (TLR)-4 stimulated monocyte production of intracellular cytokines (ICCs) via lipopolysaccharide (LPS). We evaluated relationships between AUD and ICC production at rest and after LPS stimulation. METHODS: We analyzed blood samples from 36 participants (AUD N = 14; Controls N = 22), collected across time, with ICC expression assessed at rest (i.e., unstimulated) and following stimulation with LPS (i.e., a total of 5 repeated unstimulated or stimulated measures/participant). Markers assessed included tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), TNF-α and IL-6 co-expression, and interferon (IFN). For each marker, we constructed linear mixed models with AUD, LPS, and timepoint as fixed effects (BMI as covariate), allowing for random slope and intercept. AUD × LPS was included as an interaction. RESULTS: For TLR4-stimulated monocyte production of TNF-α, there were effects of AUD (p

Abstract Background Cardiovascular disease is a leading cause of death worldwide. Rates of cardiovascular disease vary both across the lifespan and between sexes. While multiple factors, including adverse life experiences, impact the development and progression of cardiovascular disease, the potential interactions of biological sex and stress history on the aged heart are unknown. To this end, we examined sex- and stress-specific impacts on left ventricular hypertrophy (VH) after aging. We hypothesized that early-life chronic stress exposure impacts behavioral and physiologic responses that predict cardiac remodeling in a sex-specific manner. Methods Histological analysis was conducted on hearts of male and female rats previously exposed to chronic variable stress during the late adolescent period (postnatal days 43–62). These animals were challenged with a forced swim test and a glucose tolerance test before aging to 15 months and again being challenged. Predictive analyses were then used to isolate factors that relate to cardiac remodeling among these groups. Results Early-life chronic stress impacted cardiac remodeling in a sex-specific manner. Among rats with a history of chronic stress, females had increased concentric VH. However, there were few associations within the female groups among individual behavioral and physiologic parameters and cardiac remodeling. While males as a group did not have VH after chronic stress, they exhibited multiple individual associations with cardiac susceptibility. Passive coping in young males and active coping in aged males related to VH in a stress history-dependent manner. Moreover, baseline corticosterone positively correlated with VH in unstressed males, while chronically-stressed males had positive correlations between VH and visceral adiposity. Conclusions These results indicate that females as a group are uniquely susceptible to the effects of early-life stress on cardiac remodeling later in life. Conversely, males have more individual differences in vulnerability, where susceptibility to cardiac remodeling relates to endocrine, metabolic, and behavioral measures depending on stress history. These results ultimately support a framework for assessing cardiovascular risk based on biological sex and prior adverse experiences.

Abstract In the arid and semi-arid Western U.S., access to water is regulated through a legal system of water rights. Individuals, companies, organizations, municipalities, and tribal entities have documents that declare their water rights. State water regulatory agencies collate and maintain these records, which can be used in legal disputes over access to water. While these records are publicly available data in all Western U.S. states, the data have not yet been readily available in digital form from all states. Furthermore, there are many differences in data format, terminology, and definitions between state water regulatory agencies. Here, we have collected water rights data from 11 Western U.S. state agencies, harmonized terminology and use definitions, formatted them for consistency, and tied them to a Western U.S.-wide shapefile of water administrative boundaries.

Rubric-based observations of pre- and inservice teachers are common practice in schools. Popular observation tools often result in minimal variation in ratings between teachers, require extensive training and time demands for raters, and provide minimal feedback for professional development. Alternatively, direct observation methods are evidenced to effectively measure instructional behaviors. Applying direct observation to audio recordings would produce quantitative scores and provide valuable feedback to teachers about their instruction. As such, the purpose of the present pilot study was to examine the reliability and efficiency of using audio recordings to measure practices related to explicit instruction. Fleiss's kappa was modeled to determine the reliability of multiple raters. Regression and correlation examined the strength and direction of the relationship between the full length of a teacher's lesson and the first 20 min of the lesson. Results indicate that using audio recordings is reliable with kappas ranging from 0.45 to 0.80. Based on regression analyses, the first 20 min of a teacher's lesson is predictive of the rates of behaviors observed in a full lesson. Correlations suggest large, positive relationships between rates of behaviors in the first 20 min and the full lesson. Recommendations for future studies of audio-recorded observations and progress monitoring teacher behavior are discussed.

Late life insomnia may increase risk for accelerated biological aging. Intervening to treat insomnia may provide protection from biological aging by reducing the prevalence of senescent cells in the immune system, as indicated by gene expression of a marker of cellular senescence, p16INK4a. In the present study, we determine whether treatment of insomnia in older adults with cognitive behavioral therapy for insomnia (CBT-I) would reduce p16INK4a gene expression in peripheral blood mononuclear cells (PBMC), compared to a sleep education therapy (SET), an active comparator condition. Secondly, we investigate the relationship between sustained insomnia remission and reduced expression of p16INK4a. Participants 60 + years old with insomnia were enrolled in a randomized controlled trial and assigned to CBT-I or SET. Analyses of 231 older adults (CBT-I = 119; SET = 112) examine baseline, post (2 months), and 24 months gene expression of p16INK4a. Compared to baseline, expression of p16INK4a increased in the SET group over 24 months (P = 0.03), but showed no change in the CBT-I group. Those who received CBT-I and experienced sustained remission of insomnia had a significant decline in p16INK4a expression by 24 months compared to baseline (P = 0.02). Individuals not sustaining remission of insomnia exhibited overall increase expression of p16INK4a by 24 months (P = 0.03). In older adults with insomnia, p16INK4a increases over 24 months, while CBT-I treatment of insomnia mitigates the increase in p16INK4a. Further, sustained remission of insomnia using CBT-I leads to a decrease in p16INK4a. These results suggest that behavioral interventions that are effective at treating insomnia might reduce the population of senescent cells in circulating blood.

Introduction  Long sleep duration is associated with many health risks, particularly in older adults, but little is known about other characteristics associated with long sleep duration. Methods  Across 5 sites, adults aged 60-80 years who reported sleeping 8-9 h ("long sleepers", n = 95) or 6-7.25 h ("average sleepers", n = 103) were assessed for two weeks using actigraphy and sleep diary. Demographic and clinical characteristics, objective sleep apnea screening, self-reported sleep outcomes, and markers of inflammation and glucose regulation were measured. Results  Compared to average sleepers, long sleepers had a greater likelihood of being White and unemployed and/or retired. Long sleepers also reported longer time in bed, total sleep time and wake after sleep onset by sleep diary and by actigraphy. Other measures including medical co-morbidity, apnea/hypopnea index, sleep related outcomes such as sleepiness, fatigue, depressed mood, or markers of inflammation and glucose metabolism did not differ between long and average sleepers. Conclusion  Older adults with long sleep duration were more likely to be White, report unemployment and retirement suggesting the social factors or related sleep opportunity contributed to long sleep duration in the sample. Despite known health risks of long sleep duration, neither co-morbidity nor markers of inflammation or metabolism differed in older adults with long sleep duration compared with those with average sleep duration.

Physicians are experiencing epidemic levels of work-related stress and burnout. Determine efficacy of mindfulness meditation delivered as a hybrid (in-person and digital) format to reduce perceived stress in pediatric residents. Pediatric residents (n = 66) were block randomized to a hybrid Mindful Awareness Practices (MAPs) intervention, comprised of one in-person 60-min session and 6-week access to a digitally delivered MAPs curriculum (n = 27) or wait-list control (n = 39). Perceived Stress Scale (PSS) was administered at baseline and post-intervention as the primary outcome measure. A priori secondary outcomes were measured using the Abbreviated Maslach Burnout Inventory-9, Beck Depression Inventory, Beck Anxiety Inventory, UCLA Loneliness Scale, and Pittsburgh Sleep Quality Index. After the first session, 58% participated at least one digital session (M = 2.0; SD = 1.3). MAPs participants showed significant decrease in PSS compared to controls, with between-group mean difference of 2.20 (95% CI 0.47-3.93) at post-intervention (effect size 0.91; 0.19-1.62). No secondary outcome group differences were detected. Exposure to a hybrid mindfulness intervention was associated with improvement in perceived stress among pediatric residents.Trial Registration: NCT03613441.

Background: Sex differences in immune-based disorders are well-established, with female sex associated with a markedly heightened risk of autoimmune disease. Female sex is also overrepresented in other conditions associated with elevated inflammation, including depression, chronic pain, and chronic fatigue. The mechanisms underlying these disparities are unclear. This study used an experimental model of inflammatory challenge to interrogate molecular mechanisms that may contribute to female vulnerability to disorders with an inflammatory basis. Method: In this analysis of a secondary outcome from a randomized controlled trial, 111 participants (67 female) received either a bolus injection of endotoxin (n = 59) or placebo (n = 52). Participants provided blood samples before and 0.5 h post-injection for assessment of differential activation of key pro-inflammatory (i.e., activator protein (AP)-1; nuclear factor (NF)-κB) and immunoregulatory (i.e., glucocorticoid receptor (GR); cAMP response element binding protein (CREB)) signaling pathways via genome-wide expression profiling and promoter-based bioinformatics analyses. Results: Relative to males, females exhibited greater endotoxin-induced increases in bioinformatic measures of CREB transcription factor activity (p's

Breeding programs around the world continually collect data on large numbers of individuals. To be able to combine data collected across regions, years, and experiments, research communities develop standard operating procedures for data collection and measurement. One such method is a crop ontology, or a standardized vocabulary for collecting data on commonly measured traits. The ontology is also computer readable to facilitate the use of data management systems such as databases. Blueberry breeders and researchers across the United States have come together to develop the first standardized crop ontology in blueberry (Vaccinium spp.). We provide an overview and report on the construction of the first blueberry crop ontology and the 178 traits and methods included within. Researchers of Vaccinium species—such as other blueberry species, cranberry, lingonberry, and bilberry—can use the described crop ontology to collect phenotypic data of greater quality and consistency, interoperability, and computer readability. Crop ontologies, as a shared data language, benefit the entire worldwide research community by enabling collaborative meta-analyses that can be used with genomic data for quantitative trait loci, genome-wide association studies, and genomic selection analysis.

AbstractSleep loss heightens pain sensitivity, but the pathways underlying this association are not known. Given that experimental sleep disruption induces increases in cellular inflammation as well as selective loss of slow wave, N3 sleep, this study examined whether these mechanisms contribute to pain sensitivity following sleep loss in healthy adults. This assessor-blinded, cross-over sleep condition, single-site, randomized clinical trial enrolled 95 healthy adults (mean [SD] age, 27.8 [6.4]; female, 44 [53.7%]). The 2 sleep conditions were 2 nights of undisturbed sleep (US) and 2 nights of sleep disruption or forced awakening (FA, 8 pseudorandomly distributed awakenings and 200 minutes wake time during the 8-hour sleep opportunity), administered in a cross-over design after 2 weeks of washout and in a random order (FA-US; US-FA). Primary outcome was heat pain threshold (hPTH). Sleep architecture was assessed by polysomnography, and morning levels of cellular inflammation were evaluated by Toll-like receptor-4 stimulated monocyte intracellular proinflammatory cytokine production. As compared with US, FA was associated with decreases in the amount of slow wave or N3 sleep ( P < 0.001), increases in Toll-like receptor-4 stimulated production of interleukin-6 and tumor necrosis factor-α ( P = 0.03), and decreases in hPTH ( P = 0.02). A comprehensive causal mediation analysis found that FA had an indirect effect on hPTH by decreases in N3 sleep and subsequent increases in inflammation (estimate=-0.15; 95% confidence interval, -0.30 to -0.03; P < 0.05) with the proportion mediated 34.9%. Differential loss of slow wave, N3 sleep, and increases in cellular inflammation are important drivers of pain sensitivity after sleep disruption.Clinical Trials Registration: NCT01794689.

Depression, one of the most common diseases in older adults, carries significant risk for morbidity and mortality. Because of the burgeoning population of older adults, the enormous burden of late-life depression, and the limited efficacy of current antidepressants in older adults, biologically plausible models that translate into selective depression prevention strategies are needed. Insomnia predicts depression recurrence and is a modifiable target to prevent incident and recurrent depression in older adults. Yet, it is not known how insomnia gets converted into biological- and affective risk for depression, which is critical for identification of molecular targets for pharmacologic interventions, and for refinement of insomnia treatments that target affective responding to improve efficacy. Sleep disturbance activates inflammatory signaling and primes immune responses to subsequent inflammatory challenge. In turn, inflammatory challenge induces depressive symptoms, which correlate with activation of brain regions implicated in depression. This study hypothesizes that insomnia serves as a vulnerability factor for inflammation-related depression; older adults with insomnia will show heightened inflammatory- and affective responding to inflammatory challenge as compared to those without insomnia. To test this hypothesis, this protocol paper describes a placebo-controlled, randomized, double-blind study of low dose endotoxin in older adults (n = 160; 60-80 y) with insomnia vs. comparison controls without insomnia. The aims of this study are to examine differences in depressive symptoms, measures of negative affective responding, and measures of positive affective responding as a function of insomnia and inflammatory challenge. If the hypotheses are confirmed, older adults with two "hits", insomnia and inflammatory activation, would represent a high risk group to be prioritized for monitoring and for depression prevention efforts using treatments that target insomnia or inflammation. Moreover, this study will inform the development of mechanism-based treatments that target affect responses in addition to sleep behaviors, and which might also be coupled with efforts to reduce inflammation to optimize efficacy of depression prevention.

BackgroundFailed management of unanticipated difficult airway situations contributes to significant anesthesia-related morbidity and mortality. Optimization of design and layout of difficult airway trolleys (DATs) may influence outcomes during airway emergencies. The main objective of the current study was to evaluate whether a difficult airway algorithm-based DAT with integrated cognitive aids improves efficiency and team performance in difficult airway scenarios.MethodsIn a crossover design, 16 teams (anesthetist, nurse anesthetist, assistant nurse) completed two high-fidelity simulated unanticipated difficult airway scenarios. Teams used both an algorithm-based DAT and a comparison, standard DAT, in the scenarios and were randomized to order of trolley type. Outcome measures included objective efficiency parameters, team performance assessment and subjective user-ratings. Linear mixed models ANOVA, including DAT type and order of condition as main factors, was utilized for the primary analyses of the team results.ResultsUsage of the algorithm-based DAT was associated with fewer departures from the difficult airway algorithm (p = .010), and reduced number of unnecessary drawer openings (p = .002), but no significant differences in time to retrieval of airway devices or time to first effective ventilation, compared to the standard DAT. There were no significant differences in team performance, although participants expressed strong preference for the algorithm-based DAT (all user-rated measures p

BackgroundAmong the over 5 million informal caregivers for patients with Alzheimer's disease (AD) in the United States (US), over 60% experience insomnia. Research on insomnia treatment efficacy in AD caregivers is limited. An ongoing randomized non-inferiority clinical trial, the Caregiver Sleep Research study, is evaluating whether mindfulness meditation is non-inferior to cognitive behavioral therapy for insomnia (CBT-I) in the treatment of insomnia in AD caregivers. The present report examines estimated intervention costs in this ongoing trial.MethodsMicro-costing was used to itemize and abstract costs of the two interventions: a mindfulness-based intervention known as mindful awareness practices for insomnia (MAP-I); and CBT-I. This approach involves collecting detailed data on resources utilized and the unit costs of those resources, thereby revealing actual resource use and economic costs for each treatment arm. Personnel time, patient time, and supplies were inventoried, and unit costs were applied. Caregiver time costs, including travel, were based on US Labor Bureau home-health aide national mean hourly wages; instructor/staff costs were based on hourly wages. Per-participant and program costs were calculated assuming individual- and group-delivery to reflect real-world implementation. Sensitivity analyses evaluated robustness of estimates.ResultsFrom the societal perspective, per-participant MAP-I costs were $1884 for individual and $1377 for group delivery; for CBT-I, these costs were $3978 and $1981, respectively. Compared with CBT-I, MAP-I provided cost savings of $2094 (53%) and $604 (30%) per treated caregiver for individual and group delivery, respectively. From the US healthcare system perspective, MAP-I vs. CBT-I participant savings were $1872 (65%) for individual and $382 (44%) for group interventions, respectively. For MAP-I and CBT-I, instructor in-class time was the highest cost component. Results were most sensitive to combined instructor time costs.ConclusionsTreatment of insomnia with MAP-I, compared to CBT-I, yields substantial cost savings for society and the healthcare system. With this potential for cost savings, results of the ongoing non-inferiority trial have critical implications for insomnia treatment dissemination and its benefits to AD caregivers and other community populations with insomnia.

Multi-Tiered System of Support (MTSS), as a fully integrated set of practices and interventions directed to academics and behavior, with emerging applications to social and emotional learning in the teaching/learning process, is very much in its ascendency in schools across the United States and elsewhere. As a result, there is an emerging need to prepare teacher and administrator educators to enter the rapidly expanding number of implementing schools and districts. Requisite dispositions, skills, and knowledge germane to ensuring successful applications, sustainability, and resultant student outcomes from MTSS introduction into systems praxis are increasingly required. In this position paper, we discuss the origins of MTSS, its expansion into various areas of education in the United States, and its emerging contribution to the thorny issue of inclusion. We conclude with examination of Innovation Configuration, a heuristic to assist teacher and administrator educators in the development of course syllabi and other professional learning vehicles addressed to MTSS.

Course reading completion enhances student learning and helps deepen students' thinking about concepts and ideas presented in class. To better understand the students' reading completion and the factors which impact course reading completion, the researchers engaged in a study with 434 students enrolled in six graduate level literacy courses, or 28 classes, over nine years from 2009 through 2017. The researchers share the results and discuss recommendations to improve reading completion rates.

The clinical internship--also called student teaching--represents one of the most important experiences of teacher preparation programs nationwide yet remains not well understood. This article focuses on the experiences of teacher candidates who have struggled in their schools. Here we present data from a survey administered to 107 undergraduate and graduate teacher candidates (49 in elementary grades, 58 in secondary grades); we find that 7/107 (6.5%) respondents indicated imperfect placements. We then present data from semistructured follow-up interviews with those who struggled, using a constant comparative method for coding and analysis. Participants described five main categories of imperfection in clinical internship: "overwhelming responsibility, a lack of support, negative mentors, overly controlled or constrained teaching contexts," and "poor or negative feedback about teaching." We discuss what these findings might mean and suggest that inclusive coteaching models have the potential to ameliorate some imperfections, perhaps ultimately improving the work of the teachers our students become.

The use of prostate-specific membrane antigen–positron emission tomography (PSMA-PET) is becoming more widespread for the diagnosis and management of prostate cancer. Here we report a case of oligometastatic renal cell carcinoma (RCC) to the testes diagnosed incidentally on PSMA-PET imaging. This case demonstrates the potential for diagnosis of nonprostate disease with PSMA-PET imaging, as well as the promising nature of PSMA-PET for the diagnosis and surveillance of RCC. In addition, this case report discusses the rare occurrence of oligometastatic RCC to the testis.

Abstract As today’s most prevalent and costly healthcare-associated infection, hospital-onset Clostridioides difficile infection (HO-CDI) represents a major threat to patient safety world-wide. This review will discuss how new insights into the epidemiology of CDI have quantified the prevalence of C. difficile (CD) spore contamination of the patient-zone as well as the role of asymptomatically colonized patients who unavoidable contaminate their near and distant environments with resilient spores. Clarification of the epidemiology of CD in parallel with the development of a new generation of sporicidal agents which can be used on a daily basis without damaging surfaces, equipment, or the environment, led to the research discussed in this review. These advances underscore the potential for significantly mitigating HO-CDI when combined with ongoing programs for optimizing the thoroughness of cleaning as well as disinfection. The consequence of this paradigm-shift in environmental hygiene practice, particularly when combined with advances in hand hygiene practice, has the potential for significantly improving patient safety in hospitals globally by mitigating the acquisition of CD spores and, quite plausibly, other environmentally transmitted healthcare-associated pathogens.

Emerging evidence suggests that interleukin (IL)-8 has a protective role in the context of depression. Higher levels of IL-8 are associated with lower depressive symptom severity among depressed patients, and treatment-related increases in IL-8 correlate with a positive response in depressed patients. This study (a secondary analysis of a completed randomized controlled trial) aimed to examine whether higher levels of IL-8 mitigate increases in depressed mood in response to an experimental model of inflammation induced depression. Given epidemiologic relationships identified between IL-6, tumor necrosis factor (TNF)- α, and subsequent depression, levels of these pro-inflammatory cytokines were also explored as potential moderators of depressed mood response to endotoxin. Secondary analyses were completed on data from healthy adults (n = 114) who completed a double-blind, placebo-controlled randomized trial in which participants were randomly assigned to receive either a single infusion of low-dose endotoxin (derived from Escherichia coli; 0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline). IL-8, as well as IL-6 and TNF- α, were measured at baseline prior to infusion, and depressed mood and feelings of social disconnection were assessed approximately hourly. Baseline levels of IL-8, but not IL-6 or TNF-α, moderated depressed mood (β = - 0.274, p = .03) and feelings of social disconnection (β = - 0.307, p = .01) responses, such that higher baseline IL-8 was associated with less increase in depressed mood and feelings of social disconnection in the endotoxin, but not placebo, condition. IL-8 had threshold effects, in which highest quartile IL-8 (≥ 2.7 pg/mL) attenuated increases in depressed mood in response to endotoxin as compared to lower IL-8 quartiles (p = .02). These findings suggest that IL-8 may be a biological factor that mitigates risk of inflammation-associated depression. Clinical trials registration: ClinicalTrials.gov NCT01671150, registration date 23/08/2012.

The rewarding effect of opiates is mediated through dissociable neural systems in drug naïve and drug-dependent states. Neuroadaptations associated with chronic drug use are similar to those produced by chronic pain, suggesting that opiate reward could also involve distinct mechanisms in chronic pain and pain-naïve states. We tested this hypothesis by examining the effect of dopamine (DA) antagonism on morphine reward in a rat model of neuropathic pain.Neuropathic pain was induced in male Sprague-Dawley rats through chronic constriction (CCI) of the sciatic nerve; reward was assessed in the conditioned place preference (CPP) paradigm in separate groups at early (4-8 days post-surgery) and late (11-15 days post-surgery) phases of neuropathic pain. Minimal effective doses of morphine that produced a CPP in early and late phases of neuropathic pain were 6 mg/kg and 2 mg/kg respectively. The DA D1 receptor antagonist, SCH23390, blocked a morphine CPP in sham, but not CCI, rats at a higher dose (0.5 mg/kg), but had no effect at a lower dose (0.1 mg/kg). The DA D2 receptor antagonist, eticlopride (0.1 and 0.5 mg/kg), had no effect on a morphine CPP in sham or CCI rats, either in early or late phases of neuropathic pain. In the CPP paradigm, morphine reward involves DA D1 mechanisms in pain-naïve but not chronic pain states. This could reflect increased sensitivity to drug effects in pain versus no pain conditions and/or differential mediation of opiate reward in these two states.

Delta opioid receptor (DOR) agonists alleviate nociceptive behaviors in various chronic pain models, including neuropathic pain, while having minimal effect on sensory thresholds in the absence of injury. The mechanisms underlying nerve injury-induced enhancement of DOR function are unclear. We used a peripheral nerve injury (PNI) model of neuropathic pain to assess changes in the function and localization of DORs in mice and rats. Intrathecal administration of DOR agonists reversed mechanical allodynia and thermal hyperalgesia. The dose-dependent thermal antinociceptive effects of DOR agonists were shifted to the left in PNI rats. Administration of DOR agonists produced a conditioned place preference in PNI, but not in sham, animals, whereas the DOR antagonist naltrindole produced a place aversion in PNI, but not in sham, mice, suggesting the engagement of endogenous DOR activity in suppressing pain associated with the injury. GTPγS autoradiography revealed an increase in DOR function in the dorsal spinal cord, ipsilateral to PNI. Immunogold electron microscopy and in vivo fluorescent agonist assays were used to assess changes in the ultrastructural localization of DORs in the spinal dorsal horn. In shams, DORs were primarily localized within intracellular compartments. PNI significantly increased the cell surface expression of DORs within lamina IV-V dendritic profiles. Using neonatal capsaicin treatment, we identified that DOR agonist-induced thermal antinociception was mediated via receptors expressed on primary afferent sensory neurons but did not alter mechanical thresholds. These data reveal that the regulation of DORs following PNI and suggest the importance of endogenous activation of DORs in regulating chronic pain states.

ImportanceOlder adults with insomnia have a high risk of incident and recurrent depression. Depression prevention is urgently needed, and such efforts have been neglected for older adults.ObjectiveTo examine whether treatment of insomnia disorder with cognitive behavioral therapy for insomnia (CBT-I) compared with an active comparator condition, sleep education therapy (SET), prevents major depressive disorder in older adults.Design, setting, and participantsThis assessor-blinded, parallel-group, single-site randomized clinical trial assessed a community-based sample of 431 people and enrolled 291 adults 60 years or older with insomnia disorder who had no major depression or major health events in past year. Study recruitment was performed from July 1, 2012, to April 30, 2015. The trial protocol was modified to extend follow-up from 24 to 36 months, with follow-up completion in July 2018. Data analysis was performed from March 1, 2019, to March 30, 2020.InterventionsParticipants were randomized to 2 months of CBT-I (n = 156) or SET (n = 135).Main outcomes and measuresThe primary outcome was time to incident major depressive disorder as diagnosed by interview and Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria. Secondary outcome was sustained remission of insomnia disorder before depression event or duration of follow-up.ResultsAmong 291 randomized participants (mean [SD] age, 70.1 [6.7] years; 168 [57.7%] female; 7 [2.4%] Asian, 32 [11.0%] Black, 3 [1.0%] Pacific Islander, 241 [82.8%] White, 6 [2.1%] multiracial, and 2 [0.7%] unknown), 156 were randomized to CBT-I and 135 to SET. A total of 140 participants (89.7%) completed CBT-I and 130 (96.3%) participants completed SET (χ2 = 4.9, P = .03), with 114 (73.1%) completing 24 months of follow-up in the CBT-I group and 117 (86.7%) in the SET group (χ2 = 8.4, P = .004). After protocol modification, 92 (59.0%) of the CBT-I participants and 86 (63.7%) of the SET participants agreed to extended follow-up (χ2 = 0.7, P = .41), with 81 (51.9%) of the CBT-I participants and 77 (57.0%) of the SET group completing 36 months of follow-up (χ2 = 0.8; P = .39). Incident or recurrent major depression occurred in 19 participants (12.2%) in the CBT-I group and in 35 participants (25.9%) in the SET group, with an overall benefit (hazard ratio, 0.51; 95%, CI 0.29-0.88; P = .02) consistent across subgroups. Remission of insomnia disorder continuously sustained before depression event or during follow-up was more likely in CBT-I participants (41 [26.3%]) compared with the SET participants (26 [19.3%], P = .03). Those in the CBT-I group with sustained remission of insomnia disorder had an 82.6% decreased likelihood of depression (hazard ratio, 0.17; 95%, CI 0.04-0.73; P = .02) compared with those in the SET group without sustained remission of insomnia disorder.Conclusions and relevanceThe findings of this randomized clinical trial indicate that treatment of insomnia with CBT-I has an overall benefit in the prevention of incident and recurrent major depression in older adults with insomnia disorder. Community-level screening for insomnia concerns in older adults and wide delivery of CBT-I-based treatment for insomnia could substantially advance public health efforts to treat insomnia and prevent depression in this vulnerable older adult population.Trial registrationClinicalTrials.gov Identifier: NCT01641263.

Purpose: This study examines the efficacy of perceptual training for improving typical listeners' identification of vowels produced by individuals with dysarthria. We examined whether training on a subset of vowels can generalize to (a) untrained vowels and (b) other speakers with similar overall intelligibility. Method: Sixty naive listeners completed a pretest/posttest perceptual learning task. In the pretraining test and posttraining test, participants identified nine American English monophthongs produced by two speakers with dysarthria secondary to amyotrophic lateral sclerosis (ALS). In the 20-min training task, a two-alternative forced choice (2AFC) task with feedback trained listeners on a subset of the vowels and speakers presented in the pretraining test. Results: Vowel identification accuracy improved overall as a function of training. However, patterns of generalization between speakers and vowel types were not symmetric. Specifically, listeners generalized training from front vowels to back vowels but not vice versa. Likewise, listeners generalized from one speaker to another but not in the opposite direction. Examination of confusion matrices for the pretraining and posttraining revealed complex patterns of vowel-specific improvement. Conclusions: This study demonstrates that listeners benefit from a very simple training paradigm targeting vowels. Additionally, error patterns revealed that vowels are both resistant to and responsive to perceptual learning. Implications for future research and clinical training paradigms are discussed.