Augusta State University

National Surveys of Children’s Health (NSCH, 2016–2018) data were analyzed to determine if conjoint monitoring and screening showed stronger associations with children under 5 identified with ASD compared to monitoring alone, screening alone or no monitoring or screening; and investigate relationships between monitoring and screening across racial/ethnic subgroups. 86 of 332 children with ASD received their diagnosis in a timeframe suggesting potential monitoring and screening for identification purposes. Analyses showed that conjoint monitoring and screening and monitoring alone, but not screening alone, was associated with early identified ASD cases across race groups. Caution is warranted as interpreting NSCH monitoring and screening items solely for identification purposes is inaccurate in many cases. More research on monitoring with screening is needed.

Background Non-White children with developmental disabilities are frequently identified later than White children and therefore miss out on opportunities for early intervention (EI). Recent research indicates that conjoint monitoring and screening is more strongly associated with EI receipt than monitoring or screening alone. Objective To determine if there are racial/ethnic inequities in the conjoint receipt of monitoring and screening. Method A series of survey weighted and stratified logistic regression analyses were conducted on National Surveys of Children's Health (2016–2018) data with conjoint monitoring and screening, screening alone, monitoring alone, and non-receipt as outcomes for children aged 9–23 months of age. The primary predictor was child race/ethnicity (Black, Hispanic, Other, and White). Additional co-variates included child (e.g., Age), caretaker/family (e.g., poverty level), healthcare (e.g., usual source of healthcare), state EI policies, and city metropolitan status. Results Bivariate analyses indicated significant variation in conjoint monitoring and screening across racial/ethnic groups and covariates. Bivariate analyses showed that Black and Hispanic children had significantly lower odds of conjoint monitoring and screening receipt than White children. Multivariate analyses showed that this relationship was better accounted by co-variates. The health service variable, usual source of healthcare, had the strongest relationship with receipt of conjoint monitoring and screening. Conclusions Black and Hispanic children are less likely to receive conjoint monitoring and screening than White children. Analyses investigating the role of usual source of healthcare seem particularly promising for understanding the sources of inequities in monitoring and screening receipt.

The use of picture books in the elementary music classroom not only promotes imaginative play but also contributes to exposure and involvement in the dramatic arts. Picture books can also assist teachers and students in developing cultural knowledge and help promote inclusivity in a meaningful way within the classroom. The inclusion of ethnically diverse children’s literature, in tandem with music activities and experiences, can cultivate an environment where students see themselves. Mini-lessons presented in the article offer examples of music and literature activities that reflect the various cultures that make up today’s classroom.

This study examined the implementation of high-stakes adoption of edTPA® in one state in the year prior to consequential use of edTPA scores for teacher licensure. Using a mixed methods design, we investigated concerns of coordinators who were responsible for edTPA implementation in their institutions. We utilized the Concerns Based Adoption Model (CBAM) to understand edTPA coordinators’ Stages of Concern, the nature of the challenges they faced, and the professional development opportunities that alleviated their concerns. Based on the CBAM survey, the most common Stage of Concernfor edTPA coordinators was Management.Coordinators’ interviews revealed the nature of their concerns at different stages and how the size of their institution and supportive resources at particular times may have played a crucial role in shaping the edTPA roll-out in their institutions. The use of the CBAM framework enabled edTPA coordinators (a) to understand their own concerns about the high-stakes policy, (b) to articulate the complexities involved in implementing edTPA initiatives, and (c) to underscore the importance of relating concerns to appropriate professional development opportunities and support for themselves as well as their faculty.

Children who come from low socioeconomic neighborhoods or who lack certain socioeconomic advantages may be at risk for school failure. Of all academic skills, reading is particularly associated with success in school and in life. Camp Sharigan and the Reading Orienteering Club (ROC) are two group-centered prevention programs designed to employ group process to enhance children’s motivation to read while developing their reading skills. Results of an 8-month small-group study showed significant improvement in such critical reading skills as spelling, reading, comprehension, and sight words. While the ROC program showed success, the question of assessment is also an issue. Which assessment test would be best to measure success with the at-risk students? Two testing procedures were analyzed: Wide Range Achievement Test (WRAT-4) and the Howard Street reading assessment packet. The Howard Street packet gave a more accurate assessment of reading ability with at-risk students from low socioeconomic neighborhoods. Suggestions are offered for further research in developing and testing programs for preventing reading failure.

Objective Determine the incidence of tibial neuropathy following talus fractures and CT’s ability to stratify patients at risk for developing post-traumatic neuropathy. Materials and methods In this IRB-approved retrospective analysis, 71 talus fractures and 8 contralateral control ankle CTs were reviewed by one observer blinded to clinical information. CT evidence suggestive of tibial neurovascular bundle injury included nerve displacement, perineural fat effacement/edema, and bone touching nerve. The association between these CT findings and clinically evident tibial neuropathy was analyzed. A semi-quantitative likelihood score was assigned based on the degree of the CT findings around the nerve. Interobserver agreement was calculated between 2 other readers. Results Twenty-five percent of patients in this cohort had clinical evidence of tibial neuropathy. There was a high specificity (0.87–0.93) and negative predictive value (0.83–0.87), a moderate accuracy (0.80–0.82), but a lower sensitivity (0.33–0.56) associated with the CT findings. Among the CT findings, nerve displacement (p < 0.0001) and bone touching nerve (p = 0.01) were associated with tibial neuropathy. A likelihood score of 2–5 was associated (p = 0.007–0.015) with tibial neuropathy. The presence of tibial neuropathy and nerve recovery were not associated with hospital length of stay, while CT findings were. There was substantial agreement between the three readers: likelihood scores 2+ (k = 0.78) and 3+ (k = 0.72). Conclusions Tibial neuropathy occurs following talus fractures, and CT findings may help surgeons narrow down the number of patients requiring close neurological follow-up.

Steroid hormones are essential for the survival of all mammals. In adrenal glands and gonads, cytochrome P450 side chain cleavage enzyme (SCC or CYP11A1), catalyzes conversion of cholesterol to pregnenolone. We studied a patient with ambiguous genitalia by the absence of Müllerian ducts and the presence of an incompletely formed vagina, who had extremely high adrenocorticotropic hormone (ACTH) and reduced pregnenolone levels with enlarged adrenal glands. The testes revealed seminiferous tubules, stroma, rete testis with interstitial fibrosis and reduced number of germ cells. Electron microscopy showed that the patient’s testicular mitochondrial size was small with little SCC expression within the mitochondria. The mitochondria were not close to the mitochondria-associated ER membrane (MAM), and cells were filled with the microfilaments. Our result revealed that absence of pregnenolone is associated with organelle stress, leading to altered protein organization that likely created steric hindrance in testicular cells. Learning points Testes revealed seminiferous tubules, stroma, rete testis with interstitial fibrosis and reduced number of germ cells; Testicular mitochondrial size was small with little SCC expression within the mitochondria; Absence of pregnenolone is associated with organelle stress.

The movement and distribution of mitochondria is essential for cellular function in response to physiological demand. Thus, coordinated mitochondrial action is necessary in cell development. The molecular basis of mitochondrial redistribution depends on the different steps of protein folding as the rapid burst of movements is interrupted by variables, including environmental and hormonal stressors, such as adrenocorticotropic hormone (ACTH). In adrenal and gonads, CYP11A1, catalyzes cholesterol to pregnenolone conversion. During stress, the ER and mitochondria comes close to each other, resulting in the formation of a complex consisting of the translocase of outer mitochondrial membrane 22, steroidogenic acute regulatory protein and 3β-hydroxysteroid dehydrogenase type 2 (3βHSD2) via its intermembrane space exposed charged unstructured loop region. An excess of ACTH inhibits organelle organization and fiber formation as visualized by transmission electron microscopy. We created stress in cells by depriving serum. Next isolation of mitochondrial complex with digitonin and analysis through a native-gradient PAGE formed a 400-kDa complex in the absence of serum. However an additional complex of 650 kDa was observed with serum. Western staining of the stressed cells with Tom22, 3βHSD2 and Tim23 antibodies independently showed several fold increase in expression of Tim23 and 3βHSD2 after 8 hour and a three fold increase Tom 22 after 2 hour. The expression of mitochondrial VDAC2 or cytoplasmic calnexin was unchanged. We conclude that an increase in Tim23 expression possibly opens the TIM23 complex resulting rapid interaction with the MAM and ER proteins for faster metabolic activity.

Steroid hormones are synthesized in an acute condition but some genes are also transcriptionally active, and they are essential for survival of all mammals. The synthesis of metabolic reaction is initiated in the matrix side of mitochondria. In addition to the presence of different enzymes mitochondria has many translocases, which help in sorting and localization proteins across the subcompartments. The molecular basis of mitochondrial redistribution depends on the different steps of protein folding. In adrenal and gonads, Cytochrome P450 side chain cleavage enzyme (SCC or CYP11A1), catalyzes cholesterol to pregnenolone. We find that gradual mitochondrial import of SCC led to the association with mitochondrial translocase, Tim50. The N‐terminal is cleaved first followed by the C‐terminus amino acids, where deletion of more than ten amino acids from the C‐terminus reduced the activity and interaction with Tim50. Similarly, knocking down Tim50 ablates SCC activity and blocking complete SCC import into the inter mitochondrial membrane ablated activity. These two proteins are colocalized in the mitochondria, where amino acids 208–212 of Tim50 first interact with SCC. A mutation in either of these two proteins reduced their interaction, resulting in a metabolic and developmental disorder. Thus, the metabolism for conversion of pregnenolone depends on SCC and Tim50 together, as the negative feedback is inhibited in the absence of interaction between these two proteins, increasing ACTH levels. Support or Funding Information No This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

ZBTB38 belongs to the zinc finger protein family and contains the typical BTB domains. As a transcription factor, ZBTB38 is involved in cell regulation, proliferation and apoptosis, whereas, functional deficiency of ZBTB38 induces the human neuroblastoma (NB) cell death potentially. To have some insight into the role of ZBTB38 in NB development, high throughput RNA sequencing was performed using the human NB cell line SH-SY5Y with the deletion of ZBTB38. In the present study, 2,438 differentially expressed genes (DEGs) in ZBTB38 −/− SH-SY5Y cells were obtained, 83.5% of which was down-regulated. Functional annotation of the DEGs in the Kyoto Encyclopedia of Genes and Genomes database revealed that most of the identified genes were enriched in the neurotrophin TRK receptor signaling pathway, including PI3K/Akt and MAPK signaling pathway. we also observed that ZBTB38 affects expression of CDK4/6, Cyclin E, MDM2, ATM, ATR, PTEN, Gadd45, and PIGs in the p53 signaling pathway. In addition, ZBTB38 knockdown significantly suppresses the expression of autophagy-related key genes including PIK3C2A and RB1CC1. The present meeting provides evidence to molecular mechanism of ZBTB38 modulating NB development and targeted anti-tumor therapies.

Adrenal and gonadal mitochondrial metabolic activity requires electrons from cofactors, cholesterol and a substrate for rapid steroid synthesis, an essential requirement for mammalian survival. Substrate activity depends on its environment, which is regulated by chaperones and mitochondrial translocases. Cytochrome P450 side chain cleavage enzyme (Side Chain Cleavage enzyme/SCC or CYP11A1) catalyzes cholesterol to pregnenolone conversion although its mechanism of action is not well understood. We find that SCC is directly imported into the mitochondrial matrix, where its N-terminal sequence is cleaved sequentially, after which it becomes activated following the second cleavage that is dependent on the folding of the protein. Following integration of the SCC C-terminus into the TIM23 complex, amino acids 141-146 interact with the intermembrane-exposed Tim50 protein, forming a large complex. The absence of Tim50 or its mutation reduced enzymatic activity. For the first time, we report that a protein activated at the matrix remains mostly unfolded and is transported back to the IMS to integrate with the TIM23 translocase complex and align with the Tim50 protein. Amino acid changes that suppress the association of Tim50 with SCC ablate metabolic activity. Thus, the TIM23 complex is the central regulator of metabolism guided by Tim50.

Maria Luisa, a 16-year-old young woman from Escuintla, Guatemala, fled to the United States and is currently living in Connecticut. She fled Guatemala by herself and after a very arduous and dangerous journey through Mexico entered the United States at Brownsville, Texas. She voluntarily turned herself into US immigration authorities and asked for asylum, telling them that she feared for her life if she were returned to Guatemala. Maria Luisa was very nearly a victim of trafficking for sexual exploitation in Guatemala. According to the analysis of the International Commission against Impunity in Guatemala (CICIG) and the United Nations Children’s Fund (UNICEF), there are an estimated 48,500 direct victims of trafficking for the purpose of sexual exploitation in Guatemala. The illegal profits produced by this offense amount to 12.3 billion quetzals (1.75 billion US dollars), equivalent to 2.7% of the gross domestic product (GDP), more than the total budget that Guatemala spends to educate children and adolescents (CICIG and UNICEF 2016, p. 7).

Near infrared spectroscopy (NIRS) is an imaging-based diagnostic tool that provides non-invasive and continuous evaluation of regional tissue oxygenation in real-time. In recent years, NIRS has shown promise as a useful monitoring technology to help detect relative tissue ischemia that could lead to significant morbidity and mortality in preterm infants. However, some issues inherent in NIRS technology use on neonates, such as wide fluctuation in signals, signal dropout and low limit of detection of the device, pose challenges that may obscure reliable interpretation of the NIRS measurements using current methods of analysis. In this paper, we propose new nonparametric statistical methods to analyze mesenteric rSO2 (regional oxygenation) produced by NIRS to evaluate oxygenation in intestinal tissues and investigate oxygenation response to red blood cell transfusion (RBC) in preterm infants. Specifically, we present a mean area under the curve (MAUC) measure and a slope measure to capture the mean rSO2 level and temporal trajectory of rSO2, respectively. We develop estimation methods for the measures based on multiple imputation and spline smoothing and further propose novel nonparametric testing procedures to detect RBC-related changes in mesenteric oxygenation in preterm infants. Through simulation studies, we show that the proposed methods demonstrate improved accuracy in characterizing the mean level and changing pattern of mesenteric rSO2 and also increased statistical power in detecting RBC-related changes, as compared with standard approaches. We apply our methods to a NIRS study in preterm infants receiving RBC transfusion from Emory University to evaluate the pre- and post-transfusion mesenteric oxygenation in preterm infants.

Inhibition of specific Akt isoforms in CD8+ T cells promotes favored differentiation into memory versus effector cells, the former of which are superior in mediating anti-tumor immunity. In this study, we investigated the role of upstream PI3K isoforms in CD8+ T cell differentiation and assessed the potential use of PI3K isoform-specific inhibitors to favorably condition CD8+ T cells for adoptive cell therapy. The phenotype and proliferative ability of tumor antigen specific CD8+ T cells was assessed in the presence of PI3K-α, -β, or -δ inhibitors. Inhibition of PI3K-δ, but not PI3K-α or PI3K-β, delayed terminal differentiation of CD8+ T cells and maintained the memory phenotype, thus enhancing their proliferative ability and survival while maintaining their cytokine and granzyme B production ability. This effect was preserved in vivo after of ex vivo PI3K-δ inhibition in CD8+ T cells destined for adoptive transfer, enhancing their survival and also the anti-tumor therapeutic activity of a tumor-specific peptide vaccine. Our results outline a mechanism by which inhibitions of a single PI3K isoform can enhance the proliferative potential, function and survival of CD8+ T cells, with potential clinical implications for adoptive cell transfer and vaccine-based immunotherapies.

To modulate T cell function for cancer therapy one challenge is to selectively attenuate regulatory but not conventional CD4+ T cell subsets (Treg and Tconv). In this study we show how a functional dichotomy in Class IA PI3K isoforms in these two subsets of CD4+ T cells be exploited to target Treg while leaving Tconv intact. Studies employing isoform-specific PI3K inhibitors and a PI3Kδ-deficient mouse strain revealed that PI3Kα and PI3Kβ were functionally redundant with PI3Kδ in Tconv. Conversely, PI3Kδ was functionally critical in Treg, acting there to control TCR signaling, cell proliferation and survival. Notably, in a murine model of lung cancer, co-administration of a PI3Kδ-specific inhibitor with a tumor-specific vaccine decreased numbers of suppressive Treg and increased numbers of vaccine-induced CD8 T-cells within the tumor microenvironment, eliciting potent anti-tumor efficacy. Overall, our results offer a mechanistic rationale to employ PI3Kδ inhibitors to selectively target Treg and improve cancer immunotherapy.

Although small group instruction is often endorsed in teaching young children, teachers are rarely given explicit instruction on how to move instruction into small groups where effective adult-child interactions can take place. This study examines how 14 early childhood educators transitioned their instruction from whole to small group teaching after participating in a year-long program of professional development. The results indicate teachers’ previous definitions of “teaching as dissemination” interfered with their ability to take on new roles, design tasks, and manage time. Implications include the need for teacher educators to focus on how teaching through interaction shifts these aspects of the teaching process.

Angiotensin type 1 receptor blockers (ARBs) have been shown to be neuroprotective and neurorestorative in experimental stroke. The mechanisms proposed include anti-inflammatory, antiapoptotic effects, as well as stimulation of endogenous trophic factors leading to angiogenesis and neuroplasticity. We aimed to investigate the involvement of the neurotrophin, brain-derived neurotrophic factor (BDNF), in ARB-mediated functional recovery after stroke. To achieve this aim, Wistar rats received bilateral intracerebroventricular (ICV) injections of short hairpin RNA (shRNA) lentiviral particles or nontargeting control (NTC) vector, to knock down BDNF in both hemispheres. After 14 days, rats were subjected to 90-min middle cerebral artery occlusion (MCAO) and received the ARB, candesartan, 1 mg/kg, or saline IV at reperfusion (one dose), then followed for another 14 days using a battery of behavioral tests. BDNF protein expression was successfully reduced by about 70 % in both hemispheres at 14 days after bilateral shRNA lentiviral particle injection. The NTC group that received candesartan showed better functional outcome as well as increased vascular density and synaptogenesis as compared to saline treatment. BDNF knockdown abrogated the beneficial effects of candesartan on neurobehavioral outcome, vascular density, and synaptogenesis. In conclusion, BDNF is directly involved in candesartan-mediated functional recovery, angiogenesis, and synaptogenesis.