Hydroxyurea improves nitric oxide bioavailability in humanized sickle cell mice.

Despite advancements in disease management, sickle cell nephropathy, a major contributor to mortality and morbidity in patients, has limited therapeutic options. Previous studies indicate hydroxyurea, a commonly prescribed therapy for sickle cell disease (SCD), can reduce renal injury in SCD but the mechanisms are uncertain. Because SCD is associated with reduced nitric oxide (NO) bioavailability, we hypothesized that hydroxyurea treatment would improve NO bioavailability in the humanized sickle cell mouse. Humanized male 12-wk-old sickle (HbSS) and genetic control (HbAA) mice were treated with hydroxyurea or regular tap water for 2 wk before renal and systemic NO bioavailability as well as renal injury were assessed. Untreated HbSS mice exhibited increased proteinuria, elevated plasma endothelin-1 (ET-1), and reduced urine concentrating ability compared with HbAA mice. Hydroxyurea reduced proteinuria and plasma ET-1 levels in HbSS mice. Untreated HbSS mice had reduced plasma nitrite and elevated plasma arginase concentrations compared with HbAA mice. Hydroxyurea treatment augmented plasma nitrite and attenuated plasma arginase in HbSS mice. Renal vessels isolated from HbSS mice also had elevated nitric oxide synthase 3 (NOS3) and arginase 2 expression compared with untreated HbAA mice. Hydroxyurea treatment did not alter renal vascular NOS3, however, renal vascular arginase 2 expression was significantly reduced. These data support the hypothesis that hydroxyurea treatment augments renal and systemic NO bioavailability by reducing arginase activity as a potential mechanism for the improvement on renal injury seen in SCD mice.

Greater natriuretic response to ENaC inhibition in male versus female Sprague-Dawley rats.

Genes for the epithelial sodium channel (ENaC) subunits are expressed in a circadian manner, but whether this results in time-of-day differences in activity is not known. Recent data show that protein expression of ENaC subunits is higher in kidneys from female rats, yet females are more efficient in excreting an acute salt load. Thus, our in vivo study determined whether there is a time-of-day difference as well as a sex difference in the response to ENaC inhibition by benzamil. Our results showed that the natriuretic and diuretic responses to a single dose of benzamil were significantly greater in male compared with female rats whether given at the beginning of the inactive period [Zeitgeber time 0 (ZT0), 7 AM] or active period (ZT12, 7 PM). However, the response to benzamil was not significantly different between ZT0 and ZT12 dosing in either male or female rats. There was no difference in renal cortical α-ENaC protein abundance between ZT0 and ZT12 or males and females. Given previous reports of flow-induced stimulation of endothelin-1 (ET-1) production and sex differences in the renal endothelin system, we measured urinary ET-1 excretion to assess the effects of increased urine flow on intrarenal ET-1. ET-1 excretion was significantly increased following benzamil administration in both sexes, but this increase was significantly greater in females. These results support the hypothesis that ENaC activity is less prominent in maintaining Na+ balance in females independent of renal ET-1. Because ENaC subunit genes and protein expression vary by time of day and are greater in female rat kidneys, this suggests a clear disconnect between ENaC expression and channel activity.

Assessing speech perception in children with hearing loss: what conventional clinical tools may miss.

OBJECTIVES: This study tested the hypothesis that word recognition in a complex, two-talker masker is more closely related to real-world speech perception for children with hearing loss than testing performed in quiet or steady-state noise. DESIGN: Sixteen school-age hearing aid users were tested on aided word recognition in noise or two-talker speech. Unaided estimates of speech perception in quiet were retrospectively obtained from the clinical record. Ten parents completed a questionnaire regarding their children's ease of communication and understanding in background noise. RESULTS: Unaided performance in quiet was correlated with aided performance in competing noise, but not in two-talker speech. Only results in the two-talker masker were correlated with parental reports of their children's functional hearing abilities. CONCLUSIONS: Speech perception testing in a complex background such as two-talker speech may provide a more accurate predictor of the communication challenges of children with hearing loss than testing in steady noise or quiet.

Sex Differences in Diurnal Sodium Handling During Diet-Induced Obesity in Rats.

BACKGROUND: Emerging evidence over the past several years suggests that diurnal control of sodium excretion is sex dependent and involves the renal endothelin system. Given recent awareness of disruptions of circadian function in obesity, we determined whether diet-induced obesity impairs renal handling of an acute salt load at different times of day and whether this varies by sex and is associated with renal endothelin dysfunction. METHODS: Male and female Sprague-Dawley rats were placed on a high-fat diet for 8 weeks before assessing renal sodium handling and blood pressure. RESULTS: Male, but not female, rats on high fat had a significantly reduced natriuretic response to acute NaCl injection at the beginning of their active period that was associated with lower endothelin 1 (ET-1) excretion, lower ET-1 mRNA expression in the cortex and outer medulla as well as lower ETB receptor expression in the outer medulla of the high-fat rats. Obese males also had significantly higher blood pressure (telemetry) that was exacerbated by adding high salt to the diet during the last 2 weeks. While female rats developed hypertension with a high-fat diet, they were not salt sensitive and ET-1 excretion was unchanged. CONCLUSIONS: These data identify diet-induced obesity as a sex-specific disruptive factor for maintaining proper sodium handling. Although high-fat diets induce hypertension in both sexes, these data reveal that males are at greater risk of salt-dependent hypertension and further suggest that females have more redundant systems that can be productive against salt-sensitive hypertension in at least some circumstances.

Putting the capital "E" environment into ecological models of health.

The recent public health reawakening to the role of the built environment has largely excluded consideration of the natural environment. This exclusion is despite the fact that land conservation, or green infrastructure, supports the most fundamental human needs and healthy lifestyles. Although the contemporary public health paradigm acknowledges the environment as an important construct in an "ecological" approach to health, environmental protection is not commonly viewed as an upstream approach to preventing disease. This guest commentary suggests that environmental health research and practice should consider green infrastructure as germane to a healthy human environment.

Redefining Cancer Screening Coverage-Screening to Diagnosis.

This Viewpoint discusses financial barriers for additional diagnostic steps after patients receive abnormal cancer screening test results.

Combined hydroxyurea and ETA receptor blockade reduces renal injury in the humanized sickle cell mouse.

AIM: The objective of this study is to determine if ambrisentan (ETA selective antagonist) and hydroxyurea (HU) treatment has a synergistic effect on renal injury in sickle cell nephropathy when compared to HU treatment alone. The premise of the study is based on recent studies showing that endothelin-1 (ET-1) contributes to the pathophysiology of nephropathy in sickle cell disease (SCD) and that ETA receptor blockade improves renal function and protects against renal injury. Hydroxyurea (HU) is commonly prescribed for the treatment of SCD and has been shown to reduce renal injury in patients with SCD. METHODS: Male 12-week-old humanized sickle mice (HbSS) and their genetic controls (HbAA) were treated with vehicle, HU, ambrisentan, or HU with ambrisentan for 2 weeks and renal structure and function were assessed. RESULTS: Vehicle treated HbSS mice exhibited significant proteinuria compared to vehicle treated HbAA mice. HbSS mice also displayed significantly elevated plasma ET-1 concentrations and decreased urine osmolality compared to HbAA controls. Proteinuria was significantly lower in both HU and ambrisentan treated animals compared to vehicle treated HbSS mice; however, there was no additional improvement in HbSS mice treated with combined ambrisentan and HU. The combination of HU and ambrisentan resulted in significantly lower KIM-1 excretion, glomerular injury, and interstitial inflammation than HU alone. CONCLUSION: These findings indicate that HU and ETA receptor blockade produce similar reductions in renal injury in the humanized sickle mouse suggesting that both treatments may converge on the same mechanistic pathway.

Reliability, validity, and accuracy of the intervention selection profile-Function: A brief functional assessment tool.

The purpose of this study was to evaluate the reliability, validity, and accuracy of scores from the Intervention Selection Profile-Function (ISP-Function): a brief functional assessment tool founded upon Direct Behavior Rating (DBR) methodology. Participants included 34 teacher-student dyads. Using the ISP-Function, teachers rated the extent to which students exhibited disruptive behavior, as well as the frequency with which disruptions were met with four consequences. Ratings were completed across three 10-min sessions, during which a research assistant also collected systematic direct observation (SDO) data regarding the same behavior and consequences. Results indicated adequate temporal reliability (≥.70) was attained for the adult attention and peer attention targets across the three ratings; in contrast, up to 8-18 data points would be needed to achieve adequate reliability across the remaining targets. Findings further suggested that while ISP-Function ratings of disruptive behavior, adult attention, and peer attention were moderately to highly correlated with SDO data, correlations were in the low range for the access to items/activities and escape/avoidance targets. Finally, analysis of difference scores showed that on average, mean ISP-Function scores fell within only 0.33 to 1.81 points of mean SDO scores (on the 0-10 DBR scale). Agreement coefficients indicative of exact score agreement were less consistent, suggesting accuracy ranged from poor to substantial. Results are promising, but future research is necessary to support applied ISP-Function use. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Comparing the effects of incremental rehearsal and traditional drill on retention of mathematics facts and predicting the effects with memory.

The purpose of this study was to examine the effects of Incremental Rehearsal (IR) and traditional drill (TD) on retention of multiplication facts with 29 students in third and fourth grades with low mathematical skills. Results indicated that IR led to significantly more facts being retained, and was essentially equal to TD for efficiency as measured by number of facts retained per instructional minute. Memory scores accounted for 34% of the variance beyond mathematics calculation scores in retention of multiplication facts for the TD condition, but only 2% of the variance for the IR condition. Thus, retention of multiplication facts seems largely influenced by a student's memory skills when using less effective instructional techniques such as TD, while approaches like IR are likely effective regardless of memory skills. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Co-occurrence of academic and behavioral risk within elementary schools: Implications for universal screening practices.

The purposes of this study were twofold. The first was to use latent class analysis to identify groupings of students defined by the presence or absence of academic or behavioral risk. The second was to determine whether these groups differed across various dichotomous academic and behavioral outcomes (e.g., suspensions, office discipline referrals, statewide achievement test failure). Students (N = 1,488) were sampled from Grades 3-5. All students were screened for academic risk using AIMSweb Reading Curriculum-Based Measure and AIMSweb Mathematics Computation, and behavioral risk using the Social, Academic, and Emotional Behavior Risk Screener (SAEBRS). Latent class analyses supported the fit of a three-class model, with resulting student classes defined as low-risk academic and behavior (Class 1), at-risk academic and high-risk behavior (Class 2), and at-risk math and behavior (Class 3). Logistic regression analyses indicated the classes demonstrated statistically significant differences statewide achievement scores, as well as suspensions. Further analysis indicated that the odds of all considered negative outcomes were higher for both groups characterized by risk (i.e., Classes 2 and 3). Negative outcomes were particularly likely for Class 2, with the odds of negative behavioral and academic outcomes being 6-15 and 112-169 times more likely, respectively. Results were taken to support an integrated approach to universal screening in schools, defined by the evaluation of both academic and behavioral risk. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Screening for behavioral risk: Identification of high risk cut scores within the Social, Academic, and Emotional Behavior Risk Screener (SAEBRS).

The purpose of this study was to support the identification of Social, Academic, and Emotional Behavior Risk Screener (SAEBRS) cut scores that could be used to detect high-risk students. Teachers rated students across two time points (Time 1 n = 1,242 students; Time 2 n = 704) using the SAEBRS and the Behavioral and Emotional Screening System (BESS), the latter of which served as the criterion measure. Exploratory receiver operating characteristic (ROC) curve analyses of Time 1 data detected cut scores evidencing optimal levels of specificity and borderline-to-optimal levels of sensitivity. Cross-validation analyses of Time 2 data confirmed the performance of these cut scores, with all but one scale evidencing similar performance. Findings are considered particularly promising for the SAEBRS Total Behavior scale in detecting high-risk students. (PsycINFO Database Record

Diagnostic accuracy of a universal screening multiple gating procedure: A replication study.

The purpose of this diagnostic accuracy study was to evaluate the sensitivity and specificity (among other indicators) of three universal screening approaches, including the Social, Academic, and Emotional Behavior Risk Screener (SAEBRS), a SAEBRS-based teacher nomination tool, and a multiple gating procedure (MGP). Each screening approach was compared to the BASC-2 Behavioral and Emotional Screening System (BESS), which served as a criterion indicator of student social-emotional and behavioral risk. All data were collected in a concurrent fashion. Participants included 704 students (47.7% female) from four elementary schools within the Midwestern United States (21.6% were at risk per the BESS). Findings yielded support for the SAEBRS, with sensitivity = .93 (95% confidence interval [.89-.97]), specificity = .91 (.89-.93), and correct classification = .92. Findings further supported the MGP, which yielded sensitivity = .81 (.74-.87), specificity = .93 (.91-.95), and correct classification = .91. In contrast, the teacher nomination tool yielded questionable levels of diagnostic accuracy (sensitivity = .86 [.80-.91], specificity = .74 [.70-.78], and correct classification = .76). Overall, findings were particularly supportive of SAEBRS diagnostic accuracy, suggesting the MGP might also serve as an acceptable approach to universal screening. Other implications for practice and directions for future research are discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Use of direct behavior ratings to collect functional assessment data.

The purpose of this investigation was to evaluate the utility of Direct Behavior Rating Single Item Scale (DBR-SIS) methodology in collecting functional behavior assessment data. Specific questions of interest pertained to the evaluation of the accuracy of brief DBR-SIS ratings of behavioral consequences and determination of the type of training necessary to support such accuracy. Undergraduate student participants (N = 213; 62.0% male; 62.4% White) viewed video clips of students in a classroom setting, and then rated both disruptive behavior and 4 consequences of that behavior (i.e., adult attention, peer attention, escape/avoidance, and access to tangibles/activities). Results indicated training with performance feedback was necessary to support the generation of accurate disruptive behavior and consequence ratings. Participants receiving such support outperformed students in training-only, pretest-posttest, and posttest-only groups for disruptive behavior and all 4 DBR-SIS consequence targets. Future directions for research and implications for practice are discussed, including how teacher ratings may be collected along with other forms of assessment (e.g., progress monitoring) within an efficient Tier 2 assessment model. (PsycINFO Database Record

Meta-analysis of the effects of academic interventions and modifications on student behavior outcomes.

The current study examined the effect of academic interventions and modifications on behavioral outcomes in a meta-analysis of 32 single-case design studies. Academic interventions included modifying task difficulty, providing instruction in reading, mathematics, or writing, and contingent reinforcement for academic performance. There was an overall small to moderate effect (ϕ = .56) on behavioral outcomes, with a stronger effect on increasing time on task (ϕ = .64) than on decreasing disruptive behavior (ϕ = .42). There was a small effect for using a performance-based contingent reinforcer (ϕ = .48). Interventions completed in an individual setting resulted in a moderate to large effects on behavior outcomes. Results of the current meta-analysis suggest that academic interventions can offer both positive academic and behavioral outcomes. Practical implications and suggestions for future research are included. (PsycINFO Database Record

Psychometric defensibility of the Social, Academic, and Emotional Behavior Risk Screener (SAEBRS) Teacher Rating Scale and multiple gating procedure within elementary and middle school samples.

The primary purposes of this investigation were to (a) continue a line of research examining the psychometric defensibility of the Social, Academic, and Emotional Behavior Risk Screener - Teacher Rating Scale (SAEBRS-TRS), and (b) develop and preliminarily evaluate the diagnostic accuracy of a novel multiple gating procedure based on teacher nomination and the SAEBRS-TRS. Two studies were conducted with elementary and middle school student samples across two separate geographic locations. Study 1 (n=864 students) results supported SAEBRS-TRS defensibility, revealing acceptable to optimal levels of internal consistency reliability, concurrent validity, and diagnostic accuracy. Findings were promising for a combined multiple gating procedure, which demonstrated acceptable levels of sensitivity and specificity. Study 2 (n=1534 students), which replicated Study 1 procedures, further supported the SAEBRS-TRS' psychometric defensibility in terms of reliability, validity, and diagnostic accuracy. Despite the incorporation of revisions intended to promote sensitivity levels, the combined multiple gating procedure's diagnostic accuracy was similar to that found in Study 1. Taken together, results build upon prior research in support of the applied use of the SAEBRS-TRS, as well as justify future research regarding a SAEBRS-based multiple gating procedure. Implications for practice and study limitations are discussed.

Increasing social initiations in children with autism: effects of a tactile prompt.

An ABAB design was used to assess the effects of a tactile prompting device (i.e., a vibrating pager) as a prompt for the social initiations of 3 children with autism during free-play activities with typically developing peers. Results indicated that the tactile prompt was effective in increasing verbal initiations for all 3 children, and responses to peers' initiations were higher for 2 participants when the tactile prompt was used. Efforts to reduce the frequency of prompts while still maintaining rates of initiations were partially successful for 1 participant.

Factors affecting sensitivity to frequency change in school-age children and adults.

PURPOSE: The factors affecting frequency discrimination in school-age children are poorly understood. The goal of the present study was to evaluate developmental effects related to memory for pitch and the utilization of temporal fine structure. METHOD: Listeners were 5.1- to 13.6-year-olds and adults, all with normal hearing. A subgroup of children had musical training. The task was a 3-alternative forced choice in which listeners identified the interval with the higher frequency tone or the tone characterized by frequency modulation (FM). The standard was 500 or 5000 Hz, and the FM rate was either 2 or 20 Hz. RESULTS: Thresholds tended to be higher for younger children than for older children and adults for all conditions, although this age effect was smaller for FM detection than for pure-tone frequency discrimination. Neither standard frequency nor modulation rate affected the child/adult difference FM thresholds. Children with musical training performed better than their peers on pure-tone frequency discrimination at 500 Hz. CONCLUSIONS: Testing frequency discrimination using a low-rate FM detection task may minimize effects related to cognitive factors like memory for pitch or training effects. Maturation of frequency discrimination does not appear to differ across conditions in which listeners are hypothesized to rely on temporal cues and place cues.

Children's perception of speech produced in a two-talker background.

PURPOSE: This study evaluated the degree to which children benefit from the acoustic modifications made by talkers when they produce speech in noise. METHOD: A repeated measures design compared the speech perception performance of children (5-11 years) and adults in a 2-talker masker. Target speech was produced in a 2-talker background or in quiet. In Experiment 1, recognition with the 2 target sets was assessed using an adaptive spondee identification procedure. In Experiment 2, the benefit of speech produced in a 2-talker background was assessed using an open-set, monosyllabic word recognition task at a fixed signal-to-noise ratio (SNR). RESULTS: Children performed more poorly than adults, regardless of whether the target speech was produced in quiet or in a 2-talker background. A small improvement in the SNR required to identify spondees was observed for both children and adults using speech produced in a 2-talker background (Experiment 1). Similarly, average open-set word recognition scores were 11 percentage points higher for both age groups using speech produced in a 2-talker background compared with quiet (Experiment 2). CONCLUSION: The results indicate that children can use the acoustic modifications of speech produced in a 2-talker background to improve masked speech perception, as previously demonstrated for adults.