Palladium-catalyzed synthesis of aryl amides through silanoate-mediated hydrolysis of nitriles

A procedure for the formation of aryl amides through the palladium-catalyzed coupling of nitriles and aryl bromides, via the formation of intermediary silanoate derived imidate species is reported. Optimization was undertaken and examples of the process are described that furnish the products in up to 86% isolated yield

Characterization of the Neurogenic Microenvironment in the Mouse Hippocampus Following Chemical-Induced Neuronal Injury

Adult neurogenesis occurs in the subgranular zone (SGZ) of the hippocampal dentate dyrus generating new dentate granule neurons and can be induced with brain injury. Resident microglia cells and infiltrating macrophages produce inflammatory molecules in response to brain injury. While inflammation has been reported to be detrimental to hippocampal neurogenesis, other studies have suggested that the localized inflammatory response and stimulation of microglial cells can promote neurogensis. The working hypothesis of this work was that activated resident mircroglia serve a supportive role during injury-induced neurogenesis in the hippocampus. To examine this hypothesis the hippocampal toxicant, trimethyltin was used (TMT; 2.3 mg/kg, i.p.) to selectively target dentate granule cell death in adolescent and 1 year-old CD-1 male mice. mRNA of proinflammatory M1 markers and anti-inflammatory M2 genes were measured during the temporal injury response were measured in subdissected DG. Within 2 d post- TMT, neuronal death was accompanied by resident microglia activation in the abscence of infiltrating peripheral macrophages, and elevations in mRNA expression of M1 markers interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosiss factor alpha (TNFα). Bromodeoxyuridine (BrdU) incorporation identified the peak time of neurogenesis as coinciding with this upregulation of M1 markers. At 14 d post-TMT new cells migrated to the GCL, expressed the mature neuronal marker NeuN. At this time of differentiation increased expression of the M2 markers IL-1 receptor antagonist (IL-1Ra), arginase 1 (AG-I), chitinase 3-like-3 (YM-1), brain derived neurotrophic factor (BDNF), glial cell line derived growth factor (GDNF), and nerve growth factor (NGF). The proliferative response was sufficient to fully repopulate neurons in the GCL and provide functional recovery. The neurogenic response to injury differs with age. In this model, fewer BrdU+ NPCs were observed in naive and injured adult hippocampus as compared to the corresponding number seen in adolescent mice. At 2 d post-TMT, a similar level of neuronal death was observed across ages, yet activated microglia were observed in the adolescent and hypertrophic process-bearing microglia in the adult. IL-1α mRNA levels were elevated in the adolescent hippocampus; IL-6 mRNA levels were elevated in the adult. In the SGZ isolated by laser capture microdissection, IL-1β was detected but not elevated bby TMT, IL-1α was elevated at both ages, while IL-6 was elevated only in the adult. Naive NPCs isolated from the hippocampus expressed transcripts for IL-1R1, IL-6Rα, and gp-130 with significantly higher levels of IL-6Rα mRNA in the adult. In vitro, IL-1α (150 pg/ml) stimulated proliferation of adolescent and adult NPCs. Microarray analysis of the SGZ post-TMT indicated a prominence of IL- 1α/IL-1R1 signaling in the adolescent and IL-6/gp130 signaling in the adult

Racial disparities in calculated risk for bronchopulmonary dysplasia: A dataset

Bronchopulmonary dysplasia (BPD) is a severe pulmonary complication of prematurity and is associated with significant morbidity or death. Early use of systemic corticosteroids may alter the trajectory of the disease and improve outcomes. A BPD Outcomes estimator, developed by the NICHD using a large population dataset, can be used to calculate individual risk. Risk above a certain threshold may indicate that the benefits of corticosteroids outweigh the risks. Empiric analysis of this calculator by systematic entry of synthetic patient information reveals a marked racial disparity; black infants have lower risk of moderate/severe BPD due to a higher risk of death despite equivalent severity of illness. Interpretation and analysis of this finding can be found in The challenge of risk stratification of preterm infants in the setting of competing and disparate healthcare outcomes [1]. In this report, we provide the underlying data used in this analysis. Calculator output for 108 example patients, systematically varied by sex, birthweight, race, type of ventilator, and fraction of inspired oxygen (Fi

Bridge House Restoration

Bridge House was severely neglected for years since its creation. Our team’s primary objective was to rejuvenate the structure and once again make it a priority destination for the public when visiting the Experimental Structures Laboratory. With this goal in mind, we replaced the plywood barricades with guard railings designed and fabricated by the team to complement those installed on the structure by the previous group. With the elimination of the plywood barricades, the Bridge House could once again be a sense of pride in the rich historical landscape of our Cal Poly community. In addition, our team hoped to gain more knowledge and experience in working in an interdisciplinary group. An important goal for us was to have an experience that mimicked a true construction project. Throughout the experience, we expected collaboration between each discipline from the pre-construction phase through the final closeout of the structure. We aimed to embrace the Cal Poly spirit of learn by doing, by designing, welding and installing the guardrails around the structure by hand. At the end of this project, we hoped the team would gain experience in the collaboration of design, scheduling, budgeting, welding and manufacturing

Variation in ampicillin dosing for lower respiratory tract infections and neonatal bacterial infections in US children\u27s hospitals

OBJECTIVE: We examined ampicillin dosing in pediatric patients across 3 conditions: (1) bacterial lower respiratory tract infections (LRTIs) in infants and children \u3e3 months, (2) neonates with suspected or proven sepsis, and (3) neonates with suspected central nervous system (CNS) infections. We compared our findings to dosing guidance for these specific indications. DESIGN: Retrospective cohort study. SETTING: The study included data from 32 children\u27s hospitals in the United States. METHODS: We reviewed prescriptions from the SHARPS study of antimicrobials, a survey of antibiotic prescribing from July 2016 to December 2017. Prescriptions were analyzed for indication, total daily dose per kilogram, and presence of antimicrobial stewardship program (ASP) review. LRTI prescriptions were compared to IDSA recommendations for community-acquired pneumonia. Neonatal prescriptions were compared to recommendations from the American Academy of Pediatrics (AAP). Prescriptions were categorized as optimal (80%-120% of recommended dosing), suboptimal (\u3c80% of recommended dosing), or excessive (\u3e120% of recommended dosing). RESULTS: Among 1,038 ampicillin prescriptions, we analyzed 88 prescriptions for LRTI, 499 prescriptions for neonatal sepsis, and 27 prescriptions for neonatal CNS infection. Of the LRTI prescriptions, 77.3%were optimal. Of prescriptions for neonatal sepsis, 81.6% were excessive compared to AAP bacteremia recommendations but 78.8% were suboptimal compared to AAP meningitis guidelines. Also, 48.1% of prescriptions for neonatal CNS infection were suboptimal, and 50.6% of prescriptions were not reviewed by the ASP. CONCLUSIONS: LRTI dosing is generally within the IDSA-recommended range. However, dosing for neonatal sepsis often exceeds the recommendation for bacteremia but is below the recommendation for meningitis. This variability points to an important opportunity for future antimicrobial stewardship efforts

Lifespan profiles of Alzheimer's disease–associated genes and their products in monkeys and mice.

Alzheimer's disease (AD) is characterized by plaques of amyloid–beta (Aβ) peptide, cleaved from amyloid–β precursor protein (AβPP). Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice, and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AβPP mRNA, AβPP protein, and Aβ levels in rodents and primates. We also tracked a transcriptional regulator of the AβPP gene, specificity protein 1 (SP1), and the β amyloid precursor cleaving enzyme (BACE1). In mice, AβPP and Sp1 mRNA and their protein products were elevated late in life; Aβ levels declined in old age. In monkeys, Sp1, AβPP, and BACE1 mRNA declined in old age, while protein products and Aβ levels rose. Proteolytic processing in both species did not match production of Aβ. In primates, AβPP and Sp1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products, as well as Aβ levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age–related diseases