Psychometrically Valid Relationships between Acculturation and Neuropsychological Factors

Neuropsychological tests play a significant role in detecting brain dysfunction and treatment planning for patients. However, discrepancies in neurocognitive tests among ethnic minorities continue to perplex neuropsychologists and place ethnic minorities at a greater risk for misdiagnoses (Byrd et al., 2006). The aim of this study was to ascertain significant acculturation predictors influencing neuropsychological performance in ethnic minorities, particularly verbally mediated tasks which were known to be more susceptible to discrepancies in acculturation level were examined (Razani et al., 2007). Healthy participants from Hispanic (n = 52), Asian (n = 52), and Middle-Eastern (ME; n = 68) descents between the ages of 18 and 69 years were recruited. Participants were administered the acculturation scale (i.e., ARSMA) and seven neuropsychological tests (i.e., COWAT-FAS and Animals; BNT; Stroop A and B; and WASI Vocabulary and Similarities subtests). Results from reliability and exploratory factor analyses indicated that ARSMA was a reliable measure and revealed a three-factor solution (Factor 1 = Ethnic Identity, Factor 2 = Ethnic Preference, Factor 3 = Language/Heritage) as well as a higher-order factor (Acculturation). Neuropsychological measures also produced a two-factor solution (Factor 1 = Verbal Abilities, Factor 2 = Verbal Processing Speed) and a higher-order factor (Language), which were determined to be cross-culturally equivalent. When acculturation factors were regressed onto neuropsychological constructs, results indicated that Language/Heritage was the best predictor for Verbal Abilities (􀈕 = .601, p \u3c .001) and Language (􀈕 = .599, p \u3c .001); and Ethnic Preference was the best predictor for Verbal Processing Speed (􀈕 = -.194, p \u3c .05). Also, Acculturation was a significant predictor for Verbal Abilities (􀈕 = .528, p \u3c .001), Verbal Processing Speed (􀈕 =-.138, p \u3c .05), and Language (􀈕 = .371, p \u3c .001) The findings of this study are consistent with previous research demonstrating differences between Anglo-Americans and other cultural groups in neuropsychological performance (Harris et al., 2003; Manly et al., 2002; Razani et al., 2007). It is clear that similar to other demographic factors, acculturation level also needs to be taken into account when interpreting neuropsychological assessment data, to reduce misdiagnosing ethnic minorities in clinical settings

Juvenile neurogenesis makes essential contributions to adult brain structure and plays a sex-dependent role in fear memories

Postnatal neurogenesis (PNN) contributes neurons to olfactory bulb (OB) and dentate gyrus (DG) throughout juvenile development, but the quantitative amount, temporal dynamics and functional roles of this contribution have not been defined. By using transgenic mouse models for cell lineage tracing and conditional cell ablation, we found that juvenile neurogenesis gradually increased the total number of granule neurons by approximately 40% in OB, and by 25% in DG, between 2 weeks and 2 months of age, and that total numbers remained stable thereafter. These findings indicate that the overwhelming majority of net postnatal neuronal addition in these regions occurs during the juvenile period and that adult neurogenesis contributes primarily to replacement of granule cells in both regions. Behavioral analysis in our conditional cell ablation mouse model showed that complete loss of PNN throughout both the juvenile and young adult period produced a specific set of sex-dependent cognitive changes. We observed normal hippocampus-independent delay fear conditioning, but excessive generalization of fear to a novel auditory stimulus, which is consistent with a role for PNN in psychopathology. Standard contextual fear conditioning was intact, however, pre-exposure dependent contextual fear was impaired suggesting a specific role for PNN in incidental contextual learning. Contextual discrimination between two highly similar contexts was enhanced; suggesting either enhanced contextual pattern separation or impaired temporal integration. We also observed a reduced reliance on olfactory cues, consistent with a role for OB PNN in the efficient processing of olfactory information. Thus, juvenile neurogenesis adds substantively to the total numbers of granule neurons in OB and DG during periods of critical juvenile behavioral development, including weaning, early social interactions and sexual maturation, and plays a sex-dependent role in fear memories

DEVELOPMENT OF RAPID AND EFFECTIVE NANOPARTICLE-AMPLIFIED IMMUNOASSAYS TO DETECT TARGET ANALYTES

In this research, nanoparticle (NP)-amplified immunoassays were developed to detect two types of target analytes—pesticides and a protein—rapidly and effectively. These analytes are useful in developing NP-based techniques because their varied molecular weights require different ELISA methods. This dissertation contains results for three studies on mesoporous core-shell peroxidase-like Pd@Pt NPs, which can replace enzymes in ELISA-like formats. Morphology of the NPs reveal a high surface area fractal pattern, which helps explain its high catalytic activity. A competitive Pd@Pt NP-linked immunosorbent assay (NLISA) was successfully developed to detect herbicides atrazine in spiked water samples with a limit of detection (LOD) of 0.5 ng/mL and a linear range of 0.1 – 500 ng/mL. In a second study, competitive NLISAs were successfully applied to detect atrazine and acetochlor in spiked juice, fruit, and vegetable samples; results were compared to those for HPLC and a Pd@Pt NP-amplified dual-lateral flow differential pulse voltammetry immunoassay. In contrast to HPLC, the two immunoassays required simple or no sample preparation steps. Results for both immunoassays compare well to each other revealing good recoveries for spiked samples in the 87.0 – 114% range. The colorimetric catalytic intensity of Pd@Pt NPs was confirmed showing a deep blue color increasing in intensity with higher concentrations of NPs. Synthesis of antibody conjugation to NPs (Ab-NPs) was confirmed via zeta potential analysis without losing catalytic activity. Pd@Pt NP usage is extended to a macromolecule collagen type II (COL II) containing more than one epitope. The direct sandwich NLISA was developed to detect COL II in engineered tissue samples with an LOD of 0.82 ng/mL and a linear range of 3 ng/mL – 50 μg/mL. Use of NPs shows thermal stability over a 4 – 65 °C range and stability over a 7 – 9 pH range with an optimal pH of 8.5. The NP-linked immunosorbent assays have the potential for detecting multiple targets, such as pesticides and other small molecules and proteins and other macromolecules, in various fields including food and agricultural monitoring, medical diagnostics and tissue engineering

Metabolic engineering and adaptive evolution for efficient production of D-lactic acid in Saccharomyces cerevisiae

There is an increasing demand for microbial production of lactic acid (LA) as a monomer of biodegradable poly lactic acid (PLA). Both optical isomers, D-LA and L-LA, are required to produce stereocomplex PLA with improved properties. In this study, we developed Saccharomyces cerevisiae strains for efficient production of D-LA. D-LA production was achieved by expressing highly stereospecific D-lactate dehydrogenase gene (ldhA, LEUM_1756) from Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293 in S. cerevisiae lacking natural LA production activity. D-LA consumption after glucose depletion was inhibited by deleting DLD1 encoding D-lactate dehydrogenase and JEN1 encoding monocarboxylate transporter. In addition, ethanol production was reduced by deleting PDC1 and ADH1 genes encoding major pyruvate decarboxylase and alcohol dehydrogenase, respectively, and glycerol production was eliminated by deleting GPD1 and GPD2 genes encoding glycerol-3-phosphate dehydrogenase. LA tolerance of the engineered D-LA-producing strain was enhanced by adaptive evolution and overexpression of HAA1 encoding a transcriptional activator involved in weak acid stress response, resulting in effective D-LA production up to 48.9 g/L without neutralization. In a flask fed-batch fermentation under neutralizing condition, our evolved strain produced 112.0 g/L D-LA with a yield of 0.80 g/g glucose and a productivity of 2.2 g/(L center dot h)clos

Conceptualization, development, and early dissemination of eMPACTTM: A competency-based career navigation system for translational research professionals

Abstract Introduction: Purposeful training and ongoing career support are necessary to meet the evolving and expanding roles of clinical research professionals (CRP). To address the training and employment needs of clinical research coordinators (CRCs), one of the largest sectors of the CRP workforce, we designed, developed, and implemented an online career navigation system, eMPACTTM (eMpowering Purposeful Advancement of Careers and Training). Methods: A design-based research method was employed as an overarching approach that frames iterative design, development, and implementation of educational interventions. The five major phases of this project – conceptualization, task analysis for measurement development, algorithms development, algorithms validation, and system evaluation – presented specific goals and relevant methods. Results: The results reported how the eMPACTTM system was conceptualized, developed, and validated. The system allowed CRCs to navigate tailored training and job opportunities by completing their task competencies and career goals. The data sets could, in turn, support employees’ and training coordinators’ informed decisions about organizational training needs and recruitment. The early dissemination results showed steady growth in registered CRCs and diversity in users’ ethnicity and job levels. Conclusions: The eMPACTTM service showed the possibility of supporting CRCs’ individual career advancement and organizational workforce enhancement and diversity. Long-term research is needed to evaluate its impact on CRC workforce development, explore key factors influencing workforce sustainability, and expand eMPACTTM service to other CRP sectors

Induction of proliferation and monocytic differentiation of human CD34+cells by CD137 ligand signaling

10.1634/stemcells.2008-0158Stem Cells2692372-238

Structural optimization of 4-(imidazol-5-yl)pyridine derivatives affords broad-spectrum anticancer agents with selective B-RAFV600E/p38α kinase inhibitory activity: Synthesis, in vitro assays and in silico study

In the current article, we introduce design of a new series of 4-(imidazol-5-yl)pyridines with improved anticancer activity and selective B-RAF V600E /p38α kinase inhibitory activity. Based on a previous work, a group of structural modifications were applied affording the new potential antiproliferative agents. Towards extensive biological assessment of the target compounds, an in vitro anticancer assay was conducted over NCI 60-cancer cell lines panel representing blood, lung, colon, CNS, skin, ovary, renal, prostate, and breast cancers. Compounds 7c, 7d, 8b, 9b, 9c, 10c, 10d, and 11b exhibited the highest potency among the tested compounds and demonstrated sub-micromolar or one-digit micromolar GI 50 values against the majority of the employed cell lines. Compound 10c emerged as the most potent agent with nano-molar activity over most of the cells and incredible activity against melanoma (MDA-MB-435) cell line (GI 50 70 nM). It is much more potent than sorafenib, the clinically used anticancer drug, against almost all the NCI-60 cell lines. Further cell-based mechanistic assays showed that compound 10c induced cell cycle arrest and promoted apoptosis in K562, MCF-7 and HT29 cancer cell lines. In addition, compound 10c induced autophagy in the three cancer cell lines. Kinase profiling of 10c showed its inhibitory effects and selectivity towards B-RAF V600E and p38α kinases with IC 50 values of 1.84 and 0.726 µM, respectively. Docking of compound 10c disclosed its high affinity in the kinases pockets. Compound 10c represent a promising anticancer agent, that could be optimized in order to improve its kinase activity aiming at developing potential anticancer agents. The conformational stability of compound 10c in the active site of B-RAF V600E and p38α kinases was studied by applying molecular dynamic simulation of the compound in the two kinases for 600 ns in comparison to the native ligands

426. COVID-19 Infection Prevention Practices That Exceed CDC Guidance: Balancing Extra Caution Against Impediments to Care

Abstract Background At the outset of the COVID-19 pandemic, healthcare workers (HCWs) raised concerns about personal risks of acquiring infection during patient care. This led to more stringent infection prevention practices than CDC guidelines during a time of uncertainty about transmission and limited U.S. testing capacity. Hospitals were challenged to protect against true COVID-19 exposure risks, while avoiding use of unproven measures that could interfere with timely, high quality care. We evaluated hospital experiences with HCW COVID-19 exposure concerns impacting clinical workflow/management. Methods We conducted a 32-question structured survey of hospital infection prevention leaders (one per hospital) from CDC Prevention Epicenters, University of California (CA) Health system, HCA Healthcare, and the Southern CA Metrics Committee between May–Dec, 2020. We assessed facility characteristics and COVID-19 exposure concerns causing changes in respiratory care, procedure delays/modifications, requests to change infection prevention processes, disruptions in routine medical care, and health impacts of PPE overuse. Percentages were calculated among respondents for each question. Results Respondents represented 53 hospitals: 22 (42%) were small (< 200 beds), 14 (26%) medium (200-400 beds), and 17 (32%) large ( >400 beds) facilities. Of these, 11 (21%) provided Level 1 trauma care, and 22 (41%) provided highly immunocompromised patient care; 75% had cared for a substantial number of COVID-19 cases before survey completion. Majority reported changes in respiratory care delivery (71%-87%), procedural delays (75%-87%), requests to change infection prevention controls/protocols (58%-96%), and occupational health impacts of PPE overuse including skin irritation (98%) and carbon dioxide narcosis symptoms (55%) (Table). Conclusion HCW concerns over work-related COVID-19 exposure contributed to practice changes, many of which are unsupported by CDC guidance and resulted in healthcare delivery delays and alterations in clinical care. Pandemic planning and response must include the ability to rapidly develop evidence to guide infection prevention practice. Disclosures Shruti K. Gohil, MD, MPH, Medline (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnycke (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Edward Septimus, MD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Kenneth Sands, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Eunice J. Blanchard, MSN RN, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Julia Moody, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Deborah S. Yokoe, MD, MPH, Nothing to disclose Jonathan Grein, MD, Gilead (Other Financial or Material Support, Speakers fees) Stuart H. Cohen, MD, Seres (Research Grant or Support) Kimberly N. Smith, MBA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Brandon Carver, BA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Russell Poland, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Jonathan B. Perlin, MD, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Richard Platt, MD, MSc, Medline (Research Grant or Support, Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Susan S. Huang, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products

Evaluation of novel pyrazol-4-yl pyridine derivatives possessing arylsulfonamide tethers as c-Jun N-terminal kinase (JNK) inhibitors in leukemia cells

A series of 36 pyrazol-4-yl pyridine derivatives (8a-i, 9a-i, 10a-i, and 11a-i) was designed, synthesized, and evaluated for its antiproliferative activity over NCI-60 cancer cell line panel and inhibitory effect against JNK isoforms (JNK1, JNK2, and JNK3). All the synthesized compounds were tested against the NCI-60 cancer cell line panel. Compounds 11b, 11c, 11g, and 11i were selected to determine their GI50s and exerted a superior potency over the reference standard SP600125 against the tested cell lines. 11c showed a GI50 of 1.28 μM against K562 leukemic cells. Vero cells were used to assess 11c cytotoxicity compared to the tested cancer cells. The target compounds were tested against hJNK isoforms in which compound 11e exhibited the highest potency against JNK isoforms with IC50 values of 1.81, 12.7, and 10.5 nM against JNK1, JNK2, and JNK3, respectively. Kinase profiling of 11e showed higher JNK selectivity in 50 kinase panels. Compounds 11c and 11e showed cell population arrest at the G2/M phase, induced early apoptosis, and slightly inhibited beclin-1 production at higher concentrations in K562 leukemia cells relative to SP600125. NanoBRET assay of 11e showed intracellular JNK1 inhibition with an IC50 of 2.81 μM. Also, it inhibited CYP2D6 and 3A4 with different extent and its hERG activity showed little cardiac toxicity with an IC50 of 4.82 μM. hJNK3 was used as a template to generate the hJNK1 crystal structure to explore the binding mode of 11e (PDB ID: 8ENJ) with a resolution of 2.8 °A and showed a typical type I kinase inhibition against hJNK1. Binding energy scores showed that selectivity of 11e towards JNK1 could be attributed to additional hydrophobic interactions relative to JNK3