Bilinguals have been shown to outperform monolinguals on word learning and on inhibition tasks that require competition resolution. Yet the scope of such bilingual advantages remains underspecified. We compared bilinguals and monolinguals on nonverbal symbolic learning and on competition resolution while processing newly-learned material. Participants were trained on 12 tone-to-symbol mappings, combining timbre, pitch, and duration of tones. During subsequent processing, participants viewed a display with four symbols, and were instructed to identify the symbol that matched a simultaneously-presented tone. On competition trials, two symbols matched the tone in timbre and pitch, but only one matched the tone on timbre, pitch, and duration.

No learning differences emerged between 27 Spanish-English bilinguals and 27 English monolinguals, and more successful learners performed better on the Peabody Picture Vocabulary task. During the processing task, competition trials yielded responses with lower accuracies and longer latencies than control trials. Further, in both groups, more successful learning of tone-to-symbol mappings was associated with more successful retrieval during processing. In monolinguals, English receptive vocabulary scores also influenced retrieval efficiency during processing, with English/Spanish vocabulary less related to the novel processing task in bilinguals. Finally, to examine inhibition of competing stimuli, priming probes were presented after each tone-symbol processing trial. These probes suggested that bilinguals, and to a lesser extent monolinguals, showed residual inhibition of competitors at 200 ms post-target identification. Together, findings suggest that learning of novel symbolic information may depend in part on previous linguistic knowledge (not bilingualism per se), and that, during processing of newly-learned material, subtle differences in retrieval and competition resolution may emerge between bilinguals and monolinguals.

Background: Immunomodulatory drugs (IMiDs), such as lenalidomide, are therapeutically active compounds that bind and modulate the E3 ubiquitin ligase substrate recruiter cereblon, thereby affect steady-state levels of cereblon and cereblon binding partners, such as ikaros and aiolos, and induce many cellular responses, including cytotoxicity to multiple myeloma (MM) cells. Nevertheless, it takes many days for MM cells to die after IMiD induced depletion of ikaros and aiolos and thus we searched for other cereblon binding partners that participate in IMiD cytotoxicity.

Methods: Cereblon binding partners were identified from a MM cell line expressing histidine-tagged cereblon by pulling down cereblon and its binding partners and verified by co-immunoprecipitation. IMiD effects were determined by western blot analysis, cell viability assay, microRNA array and apoptosis analysis.

Results: We identified argonaute 2 (AGO2) as a cereblon binding partner and found that the steady-state levels of AGO2 were regulated by cereblon. Upon treatment of IMiD-sensitive MM cells with lenalidomide, the steady-state levels of cereblon were significantly increased, whereas levels of AGO2 were significantly decreased. It has been reported that AGO2 plays a pivotal role in microRNA maturation and function. Interestingly, upon treatment of MM cells with lenalidomide, the steady-state levels of microRNAs were significantly altered. In addition, silencing of AGO2 in MM cells, regardless of sensitivity to IMiDs, significantly decreased the levels of AGO2 and microRNAs and massively induced cell death.

Conclusion: These results support the notion that the cereblon binding partner AGO2 plays an important role in regulating MM cell growth and survival and AGO2 could be considered as a novel drug target for overcoming IMiD resistance in MM cells.

Background: Height is an important health assessment measure with many applications. In the medical practice and in research settings, height is typically measured with a stadiometer. Although lasers are commonly used by health professionals for measurement including facial imaging, corneal thickness, and limb length, it has not been utilized for measuring height. The purpose of this feasibility study was to examine the ease and accuracy of a laser device for measuring height in children and adults.

Findings: In immediate succession, participant height was measured in triplicate using a stadiometer followed by the laser device. Measurement error for the laser device was significantly higher than that for the stadiometer (0.35 and 0.20 cm respectively). However, the measurement techniques were highly correlated (r² = 0.998 and 0.990 for the younger [<12 y, n = 25] and older [≥12 y, n = 100] participants respectively), and the estimated reliability between measurement techniques was 0.999 (ICC; 95 % CI: 0.998,1.000) and 0.995 (ICC; 95 % CI: 0.993,0.997) for the younger and older groups respectively. The average differences between the two styles of measurement (e.g., stadiometer minus laser) were significantly different from zero: +0.93 and +0.45 cm for the younger and older groups respectively.

Conclusions: These data demonstrate that laser technology can be adapted to measure height in children and adults. Although refinement is needed, the laser device for measuring height merits further development.

Background: GoGirlGo! (GGG) is designed to increase girls’ physical activity (PA) using a health behavior and PA-based curriculum and is widely available for free to afterschool programs across the nation. However, GGG has not been formally evaluated. The purpose of this pilot study was to evaluate the effectiveness of the GGG curricula to improve PA, and self-efficacy for and enjoyment of PA in elementary aged girls (i.e., 5-13 years).

Methods: Nine afterschool programs were recruited to participate in the pilot (within subjects repeated measures design). GGG is a 12-week program, with a once a week, one-hour lesson with 30 minutes of education and 30 minutes of PA). Data collection occurred at baseline, mid (twice), post, and at follow-up (3-months after the intervention ended). PA was assessed via accelerometry at each time point. Self-efficacy for and enjoyment of PA was measured using the Self-Efficacy Scale and the Short-PA enjoyment scale and was assessed at baseline, post, and follow-up. Fidelity was assessed at midpoint.

Results: Across all age groups there was a statistically significant increase in PA. Overall, on days GGG was offered girls accumulated an average of 11 minutes of moderate-to-vigorous PA compared to 8 minutes during non-GGG days. There was a statistically significant difference in girls’ self-efficacy for PA reported between baseline and post, which was maintained at follow-up. An improvement in enjoyment of PA for girls was found between baseline and follow-up. According to fidelity assessment, 89% of the activities within the curriculum were completed each lesson. Girls appeared to respond well to the curriculum but girls 5-7 years had difficulties paying attention and understanding discussion questions.

Conclusions: Even though there were statistically significant differences in self-efficacy for PA and enjoyment of PA, minimal increases in girls’ PA were observed. GGG curricula improvements are warranted. Future GGG programming should explore offering GGG every day, modifying activities so that they are moderate-to-vigorous in intensity, and providing additional trainings that allow staff to better implement PA and improve behavior management techniques. With modifications, GGG could provide a promising no-cost curriculum that afterschool programs may implement to help girls achieve recommendations for PA.

Background: To examine the influence of ethnicity on liver transaminases among adolescents with type 2 diabetes mellitus (T2DM).

Methods: A retrospective medical chart review of 57 (30 males and 27 females) newly diagnosed patients with T2DM. Ethnicity was determined by self-report and height, weight, body mass index (BMI) and glycosylated hemoglobin (HbA1c) were obtained using standard clinical procedures. Fasting levels of alanine aminotransaminase (ALT) and aspartate aminotransferase (AST) were collected prior to the initiation of any therapy.

Results: Age, gender, height, weight, BMI, and HbA1c did not differ between ethnic groups. Compared to African-Americans, Hispanics had significantly higher ALT (23.9 ± 3.4 vs. 107.8 ± 20.3, p=0.002) and AST (17.7 ± 2.5 vs. 71.1 ± 15.7, p<0.001) and were significantly more likely to have ALT values above the upper limit of normal (20% vs. 71%, p=0.005) and twice the upper limit of normal (0% vs. 39%, p=0.05) as well as AST values above the upper limit of normal (0% vs. 53%, p=0.002). No differences in ALT or AST were found between Hispanics and non-Hispanic whites or between African-Americans and non-Hispanic whites.

Conclusions: These preliminary findings suggest that Hispanic children with T2DM may be at higher risk for developing non-alcoholic fatty liver disease and indicate that a comprehensive hepatic evaluation is warranted in this population. Future studies that incorporate more precise and proximal measures of liver health are warranted in this population.

Background: Health information exchange (HIE) is an important tool for improving efficiency and quality and is required for providers to meet Meaningful Use certification from the United States Centers for Medicare and Medicaid Services. However widespread adoption and use of HIE has been difficult to achieve, especially in settings such as smaller-sized physician practices and federally qualified health centers (FQHCs). We assess electronic data exchange activities and identify barriers and benefits to HIE participation in two underserved settings.

Methods: We conducted key-informant interviews with stakeholders at physician practices and health centers. Interviews were recorded, transcribed, and then coded in two waves: first using an open-coding approach and second using selective coding to identify themes that emerged across interviews, including barriers and facilitators to HIE adoption and use.

Results: We interviewed 24 providers, administrators and office staff from 16 locations in two states. They identified barriers to HIE use at three levels—regional (e.g., lack of area-level exchanges; partner organizations), inter-organizational (e.g., strong relationships with exchange partners; achieving a critical mass of users), and intra-organizational (e.g., type of electronic medical record used; integration into organization’s workflow). A major perceived benefit of HIE use was the improved care-coordination clinicians could provide to patients as a direct result of the HIE information. Utilization and perceived benefit of the exchange systems differed based on several practice- and clinic-level factors.

Conclusions: The adoption and use of HIE in underserved settings appears to be impeded by regional, inter-organizational, and intra-organizational factors and facilitated by perceived benefits largely at the intra-organizational level. Stakeholders should consider factors both internal and external to their organization, focusing efforts in changing modifiable factors and tailoring HIE efforts based on all three categories of factors. Collective action between organizations may be needed to address inter-organizational and regional barriers. In the interest of facilitating HIE adoption and use, the impact of interventions at various levels on improving the use of electronic health data exchange should be tested.

We tested the hypothesis that motor planning and programming of speech articulation and verbal short-term memory (vSTM) depend on partially overlapping networks of neural regions. We evaluated this proposal by testing 76 individuals with acute ischemic stroke for impairment in motor planning of speech articulation (apraxia of speech, AOS) and vSTM in the first day of stroke, before the opportunity for recovery or reorganization of structure-function relationships. We also evaluated areas of both infarct and low blood flow that might have contributed to AOS or impaired vSTM in each person. We found that AOS was associated with tissue dysfunction in motor-related areas (posterior primary motor cortex, pars opercularis; premotor cortex, insula) and sensory-related areas (primary somatosensory cortex, secondary somatosensory cortex, parietal operculum/auditory cortex); while impaired vSTM was associated with primarily motor-related areas (pars opercularis and pars triangularis, premotor cortex, and primary motor cortex). These results are consistent with the hypothesis, also supported by functional imaging data, that both speech praxis and vSTM rely on partially overlapping networks of brain regions.

Primary biliary cirrhosis (PBC) is a chronic progressive liver disease that often leads to fibrosis, cirrhosis, and end-stage liver disease. The diagnosis is made when there is evidence of cholestasis and reactivity to the antimitochondrial antibody. The etiology of PBC is poorly understood; however, several lines of evidence suggest an environmental factor that triggers a series of immune-mediated inflammatory reactions in the bile ducts in a genetically susceptible individual. Fatigue and pruritus are the most common symptoms of PBC; however, many patients are diagnosed with PBC only based on laboratory abnormalities. The only pharmacological treatment approved for PBC is ursodeoxycholic acid (UDCA). Several controlled studies have shown that UDCA improves liver biochemistries and prolongs transplant-free survival in PBC patients. Nearly 40% of PBC patients do not respond to UDCA, and those patients are at high risk of serious adverse events, such as the development of liver failure. Therefore, newer alternative therapeutic options for PBC are needed. Obeticholic acid is a first-in-class farnesoid X receptor agonist that has been recently evaluated in PBC patients with inadequate response to UDCA, and demonstrated beneficial results in improving liver biochemistries. Several other agents (fibrates and glucocorticoids) have been previously examined in PBC patients with inadequate response to UDCA, and preliminary results showed biochemical improvement. However, large-scale controlled clinical trials are needed to determine the long-term effects of fibrates and glucocorticoids on the clinical outcomes of PBC. Clinical trials of NGM282 (a fibroblast growth factor-19 analog) and Abatacept (a fusion protein composed of the Fc portion of immunoglobulin G1 fused to CTLA4) are currently underway.

Manual therapy has long been a component of physical rehabilitation programs, especially to treat those in pain. The mechanisms of manual therapy, however, are not fully understood, and it has been suggested that its pain modulatory effects are of neurophysiological origin and may be mediated by the descending modulatory circuit. Therefore, the purpose of this review is to examine the neurophysiological response to different types of manual therapy, in order to better understand the neurophysiological mechanisms behind each therapy’s analgesic effects. It is concluded that different forms of manual therapy elicit analgesic effects via different mechanisms, and nearly all therapies appear to be at least partially mediated by descending modulation. Additionally, future avenues of mechanistic research pertaining to manual therapy are discussed.