Hemorrhagic stroke—Pathomechanisms of injury and therapeutic options

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151916/1/cns13225_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151916/2/cns13225.pd

Pediatric Anesthesia and Neurodevelopmental Impairments: A Bayesian Meta-analysis

Experimental evidence of anesthesia-induced neurotoxicity has caused serious concern about the long-term effect of commonly used volatile anesthetic agents on young children. Several observational studies based on existing data have been conducted to address this concern with inconsistent results. We conducted a meta-analysis to synthesize the epidemiologic evidence on the association of anesthesia/surgery with neurodevelopmental outcomes in children. Using Bayesian meta-analytic approaches, we estimated the synthesized odds ratios (OR) and 95% credible interval (CrI) as well as the predictive distribution of a future study given the synthesized evidence. Data on 7 unadjusted and 6 adjusted measures of association were abstracted from 7 studies. The synthesized OR based on the 7 unadjusted measures for the association of anesthesia/surgery with an adverse behavioral or developmental outcome was 1.9 (95% CrI, 1.2-3.0). The most likely unadjusted OR from a future study was estimated to be 2.2 (95% CrI, 0.6-6.1). The synthesized OR based on the 6 adjusted measures for the association of anesthesia/surgery with an adverse behavioral or developmental outcome was 1.4 (95% CrI, 0.9-2.2). The most likely adjusted OR from a future study was estimated to be 1.5 (95% CrI, 0.5-4.0). We conclude that existent epidemiologic evidence suggests a modestly elevated risk of adverse behavioral or developmental outcomes in children who were exposed to anesthesia/surgery during early childhood. The evidence, however, is considerably uncertain

Controlling the emission efficiency of blue-green iridium (iii) phosphorescent emitters and applications in solution-processed organic light-emitting diodes

We show that the emission efficiency of blue-green phosphorescent emitters can be controlled through coupling of the excited state to vibrational modes. We controlled this vibrational coupling through choice of different ligands and as a result, complexes with CF3-groups on the ancillary ligand were essentially non-emissive (ΦPL 50%). Emission of the complexes can be drastically improved (30 times higher ΦPL compared to degassed solution for the CF3-containing complexes) by blending them with an inert solid host such as PMMA, which mitigates metal-ligand vibrations. Solution-processed organic light-emitting diodes made from these materials showed efficiency as high as 6.3%

Playground equipment-related extremity fractures in children presenting to US emergency departments, 2006–2016

Background Despite updated playground equipment and improved industry standards, playgrounds remain a common source of childhood injury. Fractures account for 35% of all playground injuries presenting to emergency departments (EDs). We aimed to examine the time trends and epidemiologic patterns of playground equipment-related extremity fractures in children in the United States. Methods We analyzed data from the National Electronic Injury Surveillance System. Children ≤14 years presenting to US emergency departments from 2006 to 2016 with playground equipment-related injuries were included. We used weighted complex survey analysis to describe the epidemiologic patterns and severity of playground equipment-related extremity fractures and Joinpoint linear weighted regression analysis to determine trends in extremity fractures. Results An annual average of 72,889 children were treated in US EDs for playground equipment-related extremity fractures, yielding a national annual incidence rate of 119.2 per 100,000 children. Playground equipment-related extremity fractures accounted for 33.9% of ED presentations and 78.7% of hospitalizations for playground equipment-related injuries. Of patients with playground equipment-related extremity fractures, 11.2% had severe fractures requiring hospitalization. The annual rate of ED visits due to playground equipment-related extremity fractures remained stable (annual rate of change = 0.74, p = 0.14) from 2006 to 2016. Adjusted for age, injuries on monkey bars or climbing gyms were associated with significantly increased odds of extremity fractures in comparison to injuries from other playground equipment (adjusted odds ratio [aOR]: 2.0; 95% CI: 1.9–2.1). Overall, 49.8% of extremity fractures and 54.7% of severe extremity fractures (i.e. those requiring hospitalization) occurred on monkey bars or climbing gyms. Conclusions Despite enhanced playground safety standards, national rates of playground equipment-related extremity fractures have remained stable in the US. Extremity fractures remain the most common type of playground injury presenting to EDs and most commonly occur on monkey bars and climbing gyms

State Medical Marijuana Laws and the Prevalence of Opioids Detected Among Fatally Injured Drivers

Objectives. To assess the association between medical marijuana laws (MMLs) and the odds of a positive opioid test, an indicator for prior use. Methods. We analyzed 1999–2013 Fatality Analysis Reporting System (FARS) data from 18 states that tested for alcohol and other drugs in at least 80% of drivers who died within 1 hour of crashing (n = 68 394). Within-state and between-state comparisons assessed opioid positivity among drivers crashing in states with an operational MML (i.e., allowances for home cultivation or active dispensaries) versus drivers crashing in states before a future MML was operational. Results. State-specific estimates indicated a reduction in opioid positivity for most states after implementation of an operational MML, although none of these estimates were significant. When we combined states, we observed no significant overall association (odds ratio [OR] = 0.79; 95% confidence interval [CI] = 0.61, 1.03). However, age-stratified analyses indicated a significant reduction in opioid positivity for drivers aged 21 to 40 years (OR = 0.50; 95% CI = 0.37, 0.67; interaction P < .001). Conclusions. Operational MMLs are associated with reductions in opioid positivity among 21- to 40-year-old fatally injured drivers and may reduce opioid use and overdose

Yes-associated protein 1 is required for proliferation and function of bovine granulosa cells in vitro

Yes-associated protein 1 (YAP1) is a major component of the Hippo signaling pathway. Although the exact extracellular signals that control the Hippo pathway are currently unknown, increasing evidence supports a critical role for the Hippo pathway in embryonic development, regulation of organ size, and carcinogenesis. Granulosa cells (GCs) within the ovarian follicle proliferate and produce steroids and growth factors, which facilitate the growth of follicle and maturation of the oocyte.We hypothesize that YAP1 plays a role in proliferation and estrogen secretion of GCs. In the current study, we examined the expression of the Hippo signaling pathway in bovine ovaries and determined whether it was important for GC proliferation and estrogen production. Mammalian STE20-like protein kinase 1 (MST1) and large tumor suppressor kinase 2 (LATS2) were identified as prominent upstream components of the Hippo pathway expressed in granulosa and theca cells of the follicle and large and small cells of the corpus luteum. Immunohistochemistry revealed that YAP1 was localized to the nucleus of growing follicles. In vitro, nuclear localization of the downstream Hippo signaling effector proteins YAP1 and transcriptional co-activator with PDZbinding motif (TAZ) was inversely correlated with GC density, with greater nuclear localization under conditions of low cell density. Treatment with verteporfin and siRNA targeting YAP1 or TAZ revealed a critical role for these transcriptional co-activators in GC proliferation. Furthermore, knockdown of YAP1 in GCs inhibited follicle-stimulating hormone (FSH)-induced estradiol biosynthesis. The data indicate that Hippo pathway transcription co-activators YAP1/TAZ play an important role in GC proliferation and estradiol synthesis, two processes necessary for maintaining normal follicle development

Early Childhood Exposure to Anesthesia and Risk of Developmental and Behavioral Disorders in a Sibling Birth Cohort

Background: In vitro and in vivo studies of anesthetics have demonstrated serious neurotoxic effects on the developing brain. However, the clinical relevance of these findings to children undergoing anesthesia remains unclear. Using data from a sibling birth cohort, we assessed the association between exposure to anesthesia in the setting of surgery in patients younger than 3 years and the risk of developmental and behavioral disorders. Methods: We constructed a retrospective cohort of 10,450 siblings who were born between 1999 and 2005 and who were enrolled in the New York State Medicaid program. The exposed group was 304 children without a history of developmental or behavioral disorders who underwent surgery when they were younger than 3 years. The unexposed group was 10,146 children who did not receive any surgical procedures when they were younger than 3 years. Exposed children were entered into analysis at the date of surgery. Unexposed children were entered into analysis at age 10 months (the mean age at which exposed children underwent surgery). Both exposed and unexposed children were followed until diagnosis with a developmental or behavioral disorder, loss to follow-up, or the end of 2005. The association of exposure to anesthesia with subsequent developmental and behavioral disorders was assessed with both proportional hazards modeling, and pair-matched analysis. Results: The incidence of developmental and behavioral disorders was 128.2 diagnoses per 1000 person-years for the exposed cohort and 56.3 diagnoses per 1000 person-years for the unexposed cohort. With adjustment for sex and history of birth-related medical complications, and clustering by sibling status, the estimated hazard ratio of developmental or behavioral disorders associated with any exposure to anesthesia when they were younger than 3 years was 1.6 (95% confidence interval [CI]: 1.4, 1.8). The risk increased from 1.1 (95% CI: 0.8, 1.4) for 1 operation to 2.9 (94% CI: 2.5, 3.1) for 2 operations and 4.0 (95% CI: 3.5, 4.5) for ≥3 operations. The relative risk in a matched analysis of 138 sibling pairs was 0.9 (95% CI: 0.6, 1.4). Conclusion: The risk of being subsequently diagnosed with developmental and behavioral disorders in children who were enrolled in a state Medicaid program and who had surgery when they were younger than 3 years was 60% greater than that of a similar group of siblings who did not undergo surgery. More tightly matched pairwise analyses indicate that the extent to which the excess risk is causally attributable to anesthesia or mediated by unmeasured factors remains to be determined

Controlling the emission efficiency of blue-green iridium(III) phosphorescent emitters and applications in solution-processed organic light-emitting diodes

We are grateful to the European Research Council (grant 321305), EPSRC (grants EP/J01771X/1, EP/L017008/1 and EP/M02105X/1) for financial support. IDWS acknowledges a Royal Society Wolfson Research Merit Award. GSH thanks the Natural Sciences and Engineering Research Council (NSERC) of Canada for funding.We show that the emission efficiency of blue-green phosphorescent emitters can be controlled through coupling of the excited state to vibrational modes. We controlled this vibrational coupling through choice of different ligands and as a result, complexes with CF3-groups on the ancillary ligand were essentially non-emissive (ΦPL 50%). Emission of the complexes can be drastically improved (30 times higher ΦPL compared to degassed solution for the CF3-containing complexes) by blending them with an inert solid host such as PMMA, which mitigates metal-ligand vibrations. Solution-processed organic light-emitting diodes made from these materials showed efficiency as high as 6.3%.PostprintPeer reviewe

Unravelling the Interfacial Dynamics of Bandgap Funneling in Bismuth-Based Halide Perovskites

An environmentally friendly mixed-halide perovskite MA3Bi2Cl9−xIx with a bandgap funnel structure has been developed. However, the dynamic interfacial interactions of bandgap funneling in MA3Bi2Cl9−xIx perovskites in the photoelectrochemical (PEC) system remain ambiguous. In light of this, single- and mixed-halide lead-free bismuth-based hybrid perovskites—MA3Bi2Cl9−yIy and MA3Bi2I9 (named MBCl-I and MBI)—in the presence and absence of the bandgap funnel structure, respectively, are prepared. Using temperature-dependent transient photoluminescence and electrochemical voltammetric techniques, the photophysical and (photo)electrochemical phenomena of solid–solid and solid–liquid interfaces for MBCl-I and MBI halide perovskites are therefore confirmed. Concerning the mixed-halide hybrid perovskites MBCl-I with a bandgap funnel structure, stronger electronic coupling arising from an enhanced overlap of electronic wavefunctions results in more efficient exciton transport. Besides, MBCl-I's effective diffusion coefficient and electron-transfer rate demonstrate efficient heterogeneous charge transfer at the solid–liquid interface, generating improved photoelectrochemical hydrogen production. Consequently, this combination of photophysical and electrochemical techniques opens up an avenue to explore the intrinsic and interfacial properties of semiconductor materials for elucidating the correlation between material characterization and device performance

Estradiol-regulated MicroRNAs Control Estradiol Response in Breast Cancer Cells

Estradiol (E2) regulates gene expression at the transcriptional level by functioning as a ligand for estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). E2-inducible proteins c-Myc and E2Fs are required for optimal ERα activity and secondary estrogen responses, respectively. We show that E2 induces 21 microRNAs and represses seven microRNAs in MCF-7 breast cancer cells; these microRNAs have the potential to control 420 E2-regulated and 757 non-E2-regulated mRNAs at the post-transcriptional level. The serine/threonine kinase, AKT, alters E2-regulated expression of microRNAs. E2 induced the expression of eight Let-7 family members, miR-98 and miR-21 microRNAs; these microRNAs reduced the levels of c-Myc and E2F2 proteins. Dicer, a ribonuclease III enzyme required for microRNA processing, is also an E2-inducible gene. Several E2-regulated microRNA genes are associated with ERα-binding sites or located in the intragenic region of estrogen-regulated genes. We propose that the clinical course of ERα-positive breast cancers is dependent on the balance between E2-regulated tumor-suppressor microRNAs and oncogenic microRNAs. Additionally, our studies reveal a negative-regulatory loop controlling E2 response through microRNAs as well as differences in E2-induced transcriptome and proteome