Are We on Course Yet? Functional Behavior Assessment and Behavior Intervention Plan Technical Adequacy in Schools.

It has been more than two decades since the Individuals with Disabilities Education Act (IDEA; 1997) included language about the use of functional behavior assessments (FBAs) and behavior intervention plans (BIPs) to address the challenging behaviors of students with disabilities in schools. It has been more than ten years since three technical adequacy studies were published that evaluated school-based FBAs' and BIPs' inclusion of essential components and found them to be significantly lacking. The aims of this study were to expand upon the previous research by (a) establishing the psychometric properties of the FBA/BIP Technical Adequacy Evaluation Tool (TATE), (b) evaluating the technical adequacy of 135 completed FBAs and 129 BIPs from 13 school districts across a single state, and (c) comparing the findings to previous studies. The results showed that (a) the TATE has moderate but acceptable internal consistency, excellent inter-rater reliability, and good content validity, (b) the technical adequacy scores of the evaluated products ranged between 40% and 50% of the total components, and (c) most of the BIPs had similar flaws to those seen in the previous research; however, improvement was noted in the FBA components. The implications for practice and suggestions for future research are discussed.

Efficacy of a Supplemental Small-Group Early Literacy Intervention Implemented by Early Childhood Educators.

PURPOSE: Phonological awareness and alphabet knowledge are fundamental building blocks for literacy development. We identified preschoolers with persistent delays in these skills and evaluated the efficacy of a supplemental curriculum to remediate deficits in early literacy skills. METHOD: Using a cluster design, 21 classrooms were randomly assigned to early literacy versus language intervention conditions. Sixty children identified through fall semester assessments of phonological awareness and alphabet knowledge were enrolled in small-group instruction. Teachers completed eLearning modules, used a digital platform to enter data and facilitate data-based decision making, received practice-based coaching, and delivered 12 weekly units of an early literacy curriculum. Comparison teachers delivered similarly administered small-group language instruction. RESULTS: Large effects were evident for letter sounds, phoneme segmentation, first sound, and first sound fluency measures (d = 0.92, 4.77, 1.15, and 1.50, respectively), and nonsignificant, small effects for letter naming and blending measures (d = 0.26 and 0.27). DISCUSSION: This early literacy intervention package had practical benefits, with 90% of experimental group preschoolers exceeding the phonemic awareness benchmark for beginning kindergarten compared to 45% in the comparison group, for example. Providing preschool teachers with tools and support for implementing a tiered approach to early literacy intervention holds promise for producing impressive gains in skills required for children to succeed in later schooling.

How host ER membrane chaperones and morphogenic proteins support virus infection.

The multi-functional endoplasmic reticulum (ER) is exploited by viruses to cause infection. Morphologically, this organelle is a highly interconnected membranous network consisting of sheets and tubules whose levels are dynamic, changing in response to cellular conditions. Functionally, the ER is responsible for protein synthesis, folding, secretion and degradation, as well as Ca2+ homeostasis and lipid biosynthesis, with each event catalyzed by defined ER factors. Strikingly, these ER host factors are hijacked by viruses to support different infection steps, including entry, translation, replication, assembly and egress. Although the full repertoire of these ER factors that are hijacked is unknown, recent studies have uncovered several ER membrane machineries that are exploited by viruses - ranging from polyomavirus to flavivirus and coronavirus - to facilitate different steps of their life cycle. These discoveries should provide better understanding of virus infection mechanisms, potentially leading to the development of more effective anti-viral therapies.

Reticulons promote formation of ER-derived double-membrane vesicles that facilitate SARS-CoV-2 replication.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiologic agent for the global COVID-19 pandemic, triggers the formation of endoplasmic reticulum (ER)-derived replication organelles, including double-membrane vesicles (DMVs), in the host cell to support viral replication. Here, we clarify how SARS-CoV-2 hijacks host factors to construct the DMVs. We show that the ER morphogenic proteins reticulon-3 (RTN3) and RTN4 help drive DMV formation, enabling viral replication, which leads to productive infection. Different SARS-CoV-2 variants, including the delta variant, use the RTN-dependent pathway to promote infection. Mechanistically, our results reveal that the membrane-embedded reticulon homology domain (RHD) of the RTNs is sufficient to functionally support viral replication and physically engage NSP3 and NSP4, two viral non-structural membrane proteins known to induce DMV formation. Our findings thus identify the ER morphogenic RTN3 and RTN4 membrane proteins as host factors that help promote the biogenesis of SARS-CoV-2-induced DMVs, which can act as viral replication platforms.

How DNA and RNA Viruses Exploit Host Chaperones to Promote Infection.

To initiate infection, a virus enters a host cell typically via receptor-dependent endocytosis. It then penetrates a subcellular membrane, reaching a destination that supports transcription, translation, and replication of the viral genome. These steps lead to assembly and morphogenesis of the new viral progeny. The mature virus finally exits the host cell to begin the next infection cycle. Strikingly, viruses hijack host molecular chaperones to accomplish these distinct entry steps. Here we highlight how DNA viruses, including polyomavirus and the human papillomavirus, exploit soluble and membrane-associated chaperones to enter a cell, penetrating and escaping an intracellular membrane en route for infection. We also describe the mechanism by which RNA viruses-including flavivirus and coronavirus-co-opt cytosolic and organelle-selective chaperones to promote viral endocytosis, protein biosynthesis, replication, and assembly. These examples underscore the importance of host chaperones during virus infection, potentially revealing novel antiviral strategies to combat virus-induced diseases.

A cluster-randomized control trial targeting parents of pediatric cancer survivors with obesity: Rationale and study protocol of NOURISH-T.

Approximately 40-50% of pediatric cancer survivors (PCS) are overweight or obese; increasing their risk for metabolic syndrome and other negative long-term physical health complications. Using our successful pilot trial testing the preliminary feasibility and efficacy of NOURISH for Healthy Transitions (NOURISH-T), we refined our intervention, now NOURISH-T+, and will implement these refinements in this larger, multi-site randomized control trial. Parents of PCS with overweight/obesity (BMI ≥ 85th%ile), age 5-12, ≥6 months off treatment are randomly assigned to the NOURISH-T+ intervention or Enhanced Usual Care (EUC) comparison. Parents in NOURISH-T+ will participate in a 6-session, manualized intervention, with an additional dietician session and 2 PCS sessions, as well as post-intervention booster sessions. EUC consists of a one-time informational session, nationally available brochures and follow-up check-ins. Both study conditions will be conducted remotely via a videoconferencing platform. Parents and PCS will be assessed on anthropometric measures, physical activity (PA) and dietary behaviors at baseline, 3-, 6-, and 12-months post-intervention. We will enroll a diverse group of 260 parents/PCS dyads from four pediatric oncology clinics with the aim of evaluating the efficacy of our intervention across diverse pediatric oncology clinics. Our main aim is to compare the impact of NOURISH-T+ with EUC on PCS BMI z-score. Secondary aims are to compare intervention impact on PCS PA and eating behaviors and parent BMI and behaviors as well as to explore potential moderators of the intervention. Our longer-term goal is to establish a framework for future translation and dissemination of NOURISH-T+.

Colon Cancer and Diverticular Disease Association: a Case-Control Study.

PURPOSE: To determine if there is an association between diverticular disease and colon cancer diagnoses with a secondary outcome of assessing other known risk factors for colon cancer. Colon cancer and diverticular disease have many shared symptoms and risk factors; the association between the two has been debated for many years. METHODS: 36 cases of colon cancer and 144 age- and sex-matched controls were identified from records at an outpatient endoscopy center in Georgia. These cases and controls then were subject to a retrospective chart review to obtain any known risk factor data points for both diverticular disease and colon cancer. A traditional conditional logistic regression and a stepwise conditional logistic regression model were used to analyze the data using significant data points (P < 0.05). RESULTS: The final stepwise model found that systolic blood pressure (aOR = 1.027, 95% CI = 1.001 to 1.053), history of polyps (aOR = 0.106, 95% CI = 0.029 to 0.387), exercise (aOR = 0.311, 95% CI = 0.029 to 0.387), and history of diverticular disease (aOR = 0.269, 95% CI = 0.091 to 0.795) were protective factors significantly associated with colon cancer. CONCLUSIONS: Presence and history of the removal of colorectal polyps, presence or history of diverticular disease, and exercise pose as protective factors against development of colon cancer.

Reticulon protects the integrity of the ER membrane during ER escape of large macromolecular protein complexes.

Escape of large macromolecular complexes from the endoplasmic reticulum (ER), such as a viral particle or cellular aggregate, likely induces mechanical stress initiated on the luminal side of the ER membrane, which may threaten its integrity. How the ER responds to this threat remains unknown. Here we demonstrate that the cytosolic leaflet ER morphogenic protein reticulon (RTN) protects ER membrane integrity when polyomavirus SV40 escapes the ER to reach the cytosol en route to infection. SV40 coopts an intrinsic RTN function, as we also found that RTN prevents membrane damage during ER escape of a misfolded proinsulin aggregate destined for lysosomal degradation via ER-phagy. Our studies reveal that although ER membrane integrity may be threatened during ER escape of large macromolecular protein complexes, the action of RTN counters this, presumably by deploying its curvature-inducing activity to provide membrane flexibility and stability to limit mechanical stress imposed on the ER membrane.

Cells Deploy a Two-Pronged Strategy to Rectify Misfolded Proinsulin Aggregates.

Insulin gene coding sequence mutations are known to cause mutant INS-gene-induced diabetes of youth (MIDY), yet the cellular pathways needed to prevent misfolded proinsulin accumulation remain incompletely understood. Here, we report that Akita mutant proinsulin forms detergent-insoluble aggregates that entrap wild-type (WT) proinsulin in the endoplasmic reticulum (ER), thereby blocking insulin production. Two distinct quality-control mechanisms operate together to combat this insult: the ER luminal chaperone Grp170 prevents proinsulin aggregation, while the ER membrane morphogenic protein reticulon-3 (RTN3) disposes of aggregates via ER-coupled autophagy (ER-phagy). We show that enhanced RTN-dependent clearance of aggregated Akita proinsulin helps to restore ER export of WT proinsulin, which can promote WT insulin production, potentially alleviating MIDY. We also find that RTN3 participates in the clearance of other mutant prohormone aggregates. Together, these results identify a series of substrates of RTN3-mediated ER-phagy, highlighting RTN3 in the disposal of pathogenic prohormone aggregates.

The effect of the Preparing Pequeños small-group cognitive instruction program on academic and concurrent social and behavioral outcomes in young Spanish-speaking dual-language learners.

Academic achievement for young dual language learners (DLL) is a critically acknowledged problem of national significance that has been understudied. To address this shortage, this study evaluated the effectiveness of Preparing Pequeños, an integrated small-group instruction program designed to promote increased learning for Spanish speaking DLL in language, literacy, and math. The DLL in the randomized Preparing Pequeños intervention classrooms were compared to control DLL with comparable Spanish language delays and in which the school district's core curriculum was being implemented. Intervention teachers and paraprofessionals, as part of Preparing Pequeños, implemented new classroom and time management systems in order to conduct 90 min of small-group instruction four days each week across the school year. In total, 51 control and 52 intervention classrooms participated; pre-test measures were completed with 829 children, with 777 of these children also completing post-test measures (7% attrition). Results showed that intervention teachers and paraprofessionals, as compared to control, showed greater increases in most of the targeted areas of cognitive instruction (d range = 0.60-2.38) and in the use of small groups (d range = 3.32-4.46), progress monitoring (d = 0.17) to inform instruction, and team teaching (d = 1.94). Intervention children, as compared to control, showed significantly greater gains in Spanish oral language, print knowledge, phonological awareness, and phonics with small to large effect sizes (d range = 0.14-0.52). Also, potentially as a result of greater attention to children's individual needs and support for managing their behavior, intervention children, as compared to control, showed greater decreases in school avoidance, anger, and aggression with small effect sizes (d range = -0.22 to -0.29). Results are discussed in relation to the need for greater attention in teachers' training in effective approaches for small-group instruction.

Bidirectional Associations Between Parental Responsiveness and Executive Function During Early Childhood.

In this study, we examined bidirectional associations between parental responsiveness and executive function (EF) processes in socioeconomically disadvantaged preschoolers. Participants were 534 3- to 5-year-old children (71% Hispanic/Latino; 28% African American; 1% European American) attending Head Start programs. At Time 1 (T1) and 6.5 months later at Time 2 (T2), parents and children participated in a videotaped free play session and children completed delay inhibition (gift delay-wrap, gift delay-bow) and conflict EF (bear/dragon, dimensional change card sort) tasks. Parental warm acceptance, contingent responsiveness, and verbal scaffolding were coded from the free play videos and aggregated to create a parental responsiveness latent variable. A cross-lagged panel structural equation model indicated that higher T1 parental responsiveness significantly predicted more positive gain in delay inhibition and conflict EF from T1 to T2. Higher T1 delay inhibition, but not T1 conflict EF, significantly predicted more positive change in parental responsiveness from T1 to T2. These associations were not explained by several possible confounding variables, including children's age, gender, race/ethnicity, and verbal ability. Findings suggest that parental responsiveness may support EF development in disadvantaged children, with reciprocal effects of delay inhibition on parental responsiveness.

SGTA-Dependent Regulation of Hsc70 Promotes Cytosol Entry of Simian Virus 40 from the Endoplasmic Reticulum.

Membrane penetration by nonenveloped viruses remains enigmatic. In the case of the nonenveloped polyomavirus simian virus 40 (SV40), the virus penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol and then traffics to the nucleus to cause infection. We previously demonstrated that the cytosolic Hsc70-SGTA-Hsp105 complex is tethered to the ER membrane, where Hsp105 and SGTA facilitate the extraction of SV40 from the ER and transport of the virus into the cytosol. We now find that Hsc70 also ejects SV40 from the ER into the cytosol in a step regulated by SGTA. Although SGTA's N-terminal domain, which mediates homodimerization and recruits cellular adaptors, is dispensable during ER-to-cytosol transport of SV40, this domain appears to exert an unexpected post-ER membrane translocation function during SV40 entry. Our study thus establishes a critical function of Hsc70 within the Hsc70-SGTA-Hsp105 complex in promoting SV40 ER-to-cytosol membrane penetration and unveils a role of SGTA in controlling this step.IMPORTANCE How a nonenveloped virus transports across a biological membrane to cause infection remains mysterious. One enigmatic step is whether host cytosolic components are co-opted to transport the viral particle into the cytosol. During ER-to-cytosol membrane transport of the nonenveloped polyomavirus SV40, a decisive infection step, a cytosolic complex composed of Hsc70-SGTA-Hsp105 was previously shown to associate with the ER membrane. SGTA and Hsp105 have been shown to extract SV40 from the ER and transport the virus into the cytosol. We demonstrate here a critical role of Hsc70 in SV40 ER-to-cytosol penetration and reveal how SGTA controls Hsc70 to impact this process.

Intracellular trafficking of bacterial toxins.

Bacterial toxins often translocate across a cellular membrane to gain access into the host cytosol, modifying cellular components in order to exert their toxic effects. To accomplish this feat, these toxins traffic to a membrane penetration site where they undergo conformational changes essential to eject the toxin's catalytic subunit into the cytosol. In this brief review, we highlight recent findings that elucidate both the trafficking pathways and membrane translocation mechanisms of toxins that cross the plasma, endosomal, or endoplasmic reticulum (ER) membrane. These findings not only illuminate the specific nature of the host-toxin interactions during entry, but should also provide additional therapeutic strategies to prevent or alleviate the bacterial toxin-induced diseases.

Effects of a Responsiveness-Focused Intervention in Family Child Care Homes on Children's Executive Function.

Caregiver responsiveness has been theorized and found to support children's early executive function (EF) development. This study examined the effects of an intervention that targeted family child care provider responsiveness on children's EF. Family child care providers were randomly assigned to one of two intervention groups or a control group. An intervention group that received a responsiveness-focused online professional development course and another intervention group that received this online course plus weekly mentoring were collapsed into one group because they did not differ on any of the outcome variables. Children (N = 141) ranged in age from 2.5 to 5 years (mean age = 3.58 years; 52% female). At pretest and posttest, children completed delay inhibition tasks (gift delay-wrap, gift delay-bow) and conflict EF tasks (bear/dragon, dimensional change card sort), and parents reported on the children's level of attention problems. Although there were no main effects of the intervention on children's EF, there were significant interactions between intervention status and child age for delay inhibition and attention problems. The youngest children improved in delay inhibition and attention problems if they were in the intervention rather than the control group, whereas older children did not. These results suggest that improving family child care provider responsive behaviors may facilitate the development of certain EF skills in young preschool-age children.

The nucleotide exchange factors Grp170 and Sil1 induce cholera toxin release from BiP to enable retrotranslocation.

Cholera toxin (CT) intoxicates cells by trafficking from the cell surface to the endoplasmic reticulum (ER), where the catalytic CTA1 subunit hijacks components of the ER-associated degradation (ERAD) machinery to retrotranslocate to the cytosol and induce toxicity. In the ER, CT targets to the ERAD machinery composed of the E3 ubiquitin ligase Hrd1-Sel1L complex, in part via the activity of the Sel1L-binding partner ERdj5. This J protein stimulates BiP's ATPase activity, allowing BiP to capture the toxin. Presumably, toxin release from BiP must occur before retrotranslocation. Here, using loss-and gain-of-function approaches coupled with binding studies, we demonstrate that the ER-resident nucleotide exchange factors (NEFs) Grp170 and Sil1 induce CT release from BiP in order to promote toxin retrotranslocation. In addition, we find that after NEF-dependent release from BiP, the toxin is transferred to protein disulfide isomerase; this ER redox chaperone is known to unfold CTA1, which allows the toxin to cross the Hrd1-Sel1L complex. Our data thus identify two NEFs that trigger toxin release from BiP to enable successful retrotranslocation and clarify the fate of the toxin after it disengages from BiP.

Parenting predictors of cognitive skills and emotion knowledge in socioeconomically disadvantaged preschoolers.

This study examined the concurrent and longitudinal associations of parental responsiveness and inferential language input with cognitive skills and emotion knowledge among socioeconomically disadvantaged preschoolers. Parents and 2- to 4-year-old children (mean age=3.21 years, N=284) participated in a parent-child free play session, and children completed cognitive (language, early literacy, early mathematics) and emotion knowledge assessments. Approximately 1 year later, children completed the same assessment battery. Parental responsiveness was coded from the videotaped parent-child free play sessions, and parental inferential language input was coded from transcripts of a subset of 127 of these sessions. All analyses controlled for child age, gender, and parental education, and longitudinal analyses controlled for initial skill level. Parental responsiveness significantly predicted all concurrent cognitive skills as well as literacy, math, and emotion knowledge 1 year later. Parental inferential language input was significantly positively associated with children's concurrent emotion knowledge. In longitudinal analyses, an interaction was found such that for children with stronger initial language skills, higher levels of parental inferential language input facilitated greater vocabulary development, whereas for children with weaker initial language skills, there was no association between parental inferential language input and change in children's vocabulary skills. These findings further our understanding of the roles of parental responsiveness and inferential language input in promoting children's school readiness skills.

Associations Among Parental Education, Home Environment Quality, Effortful Control, and Preacademic Knowledge.

This study used a longitudinal design to examine whether effortful control mediated the associations of parental education and home environment quality with preacademic knowledge in toddlers and young preschoolers. The sample consisted of 226 children (2 to 4 years of age at T1) from socioeconomically disadvantaged backgrounds. Parents provided data on parent education and home environment quality. Children completed effortful control, early literacy, and early math assessments. T2 effortful control partially mediated the associations of T1 parental education and T1 home environment quality with T3 emergent literacy after accounting for child age, gender, race/ethnicity, T1 effortful control, and T2 early literacy. T2 effortful control partially mediated the association between T1 parental education and T3 emergent math after accounting for child age, gender, race/ethnicity, T1 effortful control, and T2 early math. Prior to entry into preschool, parental education and home environment quality may shape effortful control which in turn influences preacademic knowledge.

Student mental health implications for physician assistant education.

PURPOSE: This report examines student mental health and learning disabilities along the continuum from childhood to college by examining diagnosing and prescribing patterns and potential implications for physician assistant (PA) faculty based on the Standards of the Accreditation Review Commission on Education for the Physician Assistant (ARC-PA) and the new Diagnostic and Statistical Manual of Mental Disorders (DSM-5, Section 2, Specific Learning Disorders). METHODS: We reviewed existing data to compare decades of national patterns in diagnosing and prescribing for conditions that have known comorbidities with learning disabilities. By including quantitative and qualitative data from children, adolescents, undergraduate college students, and veterans, we illustrate the potential impact these patterns could have on some current and future applicants to PA educational programs and the requirements for PA faculty to address these needs. RESULTS: Multiple national data sources revealed increasing numbers of children diagnosed with Attention Deficit Hyperactivity Disorder (ADHD), psychoactive prescriptions written for those under age 18, and self-reported increases in multiple psychological disorders among college students. More recent evidence shows a twofold increase in military veterans returning to college with posttraumatic stress disorder, traumatic brain injury, and depression. CONCLUSION: The growing numbers of students with conditions described in this report requires academic faculty to be aware of requirements to recognize and address their mental health service needs. PA educators could benefit from supplemental faculty development activities to help prepare them to recognize the pipeline patterns of a growing percentage of postsecondary students with mental health conditions and learning disabilities.

"My Baby & Me": effects of an early, comprehensive parenting intervention on at-risk mothers and their children.

This study examined the efficacy of a multimodule parenting intervention, "My Baby & Me," that began prenatally and continued until children reached 2.5 years of age. The intervention targeted specific parenting skills designed to alter trajectories of maternal and child development. Of 361 high-risk mothers (193 adolescents, 168 adults) enrolled across 4 states, half were randomly assigned to the high-intensity (HI) home visitation coaching program (55 sessions), and half to a low-intensity (LI) condition that included monthly phone calls from a coach, printed informational materials, and community resource referrals. Videotaped observations of mother-child play were coded at 5 time points for multiple maternal and child behaviors and skills. Compared to mothers in the LI group, mothers in the HI group showed higher levels of contingent responsiveness, higher quality verbal stimulation, and more verbal scaffolding by 30 months, with higher levels of warmth and greater decreases in physical intrusiveness and negativity when their children were 24 months. By 30 months, children in the HI group showed more rapid increases and higher levels of engagement with the environment, expressive language skills, and social engagement, as well as more complex toy play and fewer problem behaviors than those in the LI group. Gains in maternal responsive behaviors mediated the effects of the intervention on child outcomes. Results were comparable for adolescent and adult mothers. A strong theoretical framework, consistent focus on maternal responsiveness, high dosage, and trusting relationships with coaches are thought to explain the positive outcomes.

Longitudinal mediators of achievement in mathematics and reading in typical and atypical development.

Longitudinal studies of neurodevelopmental disorders that are diagnosed at or before birth and are associated with specific learning difficulties at school-age provide one method for investigating developmental precursors of later-emerging academic disabilities. Spina bifida myelomeningocele (SBM) is a neurodevelopmental disorder associated with particular problems in mathematics, in contrast to well-developed word reading. Children with SBM (n=30) and typically developing children (n=35) were used to determine whether cognitive abilities measured at 36 and 60 months of age mediated the effect of group on mathematical and reading achievement outcomes at 8.5 and 9.5 years of age. A series of multiple mediator models showed that: visual-spatial working memory at 36 months and phonological awareness at 60 months partially mediated the effect of group on math calculations, phonological awareness partially mediated the effect of group on small addition and subtraction problems on a test of math fluency, and visual-spatial working memory mediated the effect of group on a test of math problem solving. Groups did not differ on word reading, and phonological awareness was the only mediator for reading fluency and reading comprehension. The findings are discussed with reference to theories of mathematical development and disability and with respect to both common and differing cognitive correlates of math and reading.