A mechanistic study of the EC′ mechanism – the split wave in cyclic voltammetry and square wave voltammetry

In this paper, a detailed investigation of electrochemical reactions coupled with homogenous chemical steps using cyclic voltammetry (CV) and square wave voltammetry (SWV) was carried out to study the electrocatalytic (EC’) mechanism. In CV, parameters including scan rate, electrode material and redox reactant were investigated while in SWV, parameters including substrate concentrations and frequencies were altered to demonstrate EC’ mechanism. Mechanistic studies focused on the EC’ mechanism using L-cysteine with ferrocenecarboxylic acid and 1,1 ′-ferrocenedicarboxylic acid respectively. Voltammetric responses were recorded and under conditions of high chemical rate constant and low substrate concentration, a split wave was observed in both CV and SWV studies

Assessment of neighborhood poverty, cognitive function, and prefrontal and hippocampal volumes in children

Importance: The association between poverty and unfavorable cognitive outcomes is robust, but most research has focused on individual household socioeconomic status (SES). There is increasing evidence that neighborhood context explains unique variance not accounted for by household SES. Objective: To evaluate whether neighborhood poverty (NP) is associated with cognitive function and prefrontal and hippocampal brain structure in ways that are dissociable from household SES. Design, Setting, and Participants: This cross-sectional study used a baseline sample of the ongoing longitudinal Adolescent Brain Cognitive Development (ABCD) Study. The ABCD Study will follow participants for assessments each year for 10 years. Data were collected at 21 US sites, mostly within urban and suburban areas, between September 2019 and October 2018. School-based recruitment was used to create a participant sample reflecting the US population. Data analysis was conducted from March to June 2019. Main Outcomes and Measures: NP and household SES were included as factors potentially associated with National Institutes of Health Toolbox Cognitive Battery subtests and hippocampal and prefrontal (dorsolateral prefrontal cortex [DLPFC], dorsomedial PFC [DMPFC], superior frontal gyrus [SFG]) volumes. Independent variables were first considered individually and then together in mixed-effects models with age, sex, and intracranial volume as covariates. Structural equation modeling (SEM) was used to assess shared variance in NP to brain structure and cognitive task associations. The tested hypotheses were formulated after data collection. Results: A total of 11 875 children aged 9 and 10 years (5678 [47.8%] girls) were analyzed. Greater NP was associated with lower scores across all cognitive domains (eg, total composite: β = -0.18; 95% CI, -0.21 to -0.15; P \u3c .001) and with decreased brain volume in the DLPFC (eg, right DLPFC: β = -0.09; 95% CI, -0.12 to -0.07; P \u3c .001), DMPFC (eg, right DMPC: β = -0.07; 95% CI, -0.09 to -0.05; P \u3c .001), SFG (eg, right SFG: β = -0.05; 95% CI, -0.08 to -0.03; P \u3c .001), and right hippocampus (β = -0.04; 95% CI, -0.06 to -0.01; P = .01), even when accounting for household income. Greater household income was associated with higher scores across all cognitive domains (eg, total composite: β = 0.30; 95% CI, 0.28 to 0.33; P \u3c .001) and larger volume in all prefrontal and hippocampal brain regions (eg, right hippocampus: β = 0.04; 95% CI, 0.02 to 0.07; P \u3c .001) even when accounting for NP. The SEM model was a good fit across all cognitive domains, with prefrontal regions being associated with NP relations to language (picture vocabulary: estimate [SE], -0.03 [0.01]; P \u3c .001; oral reading: estimate [SE], -0.02 [0.01]; P \u3c .001), episodic memory (picture sequence: estimate [SE], -0.02 [0.01]; P = .008), and working memory (dimensional card sort: estimate [SE], -0.02 [0.01]; P = .001; flanker inhibitory control: estimate [SE], -0.01 [0.01]; P = .01; list sorting: estimate [SE], -0.03 [0.01]; P \u3c .001) and hippocampal regions being associated with NP associations with language (picture vocabulary: estimate [SE], -0.01 [0.004]; P \u3c .001) and episodic memory (picture sequence: estimate [SE], -0.01 [0.004]; P \u3c 0.001). Conclusions and Relevance: In this study, NP accounted for unique variance in cognitive function and prefrontal and right hippocampal brain volume. These findings demonstrate the importance of including broader environmental influences when conceptualizing early life adversity

A Flow Cytometric Assay for the Study of E3 Ubiquitin Ligase Activityb

This is the peer reviewed version of the following article: Hilliard, J. G., Cooper, A. L., Slusser, J. G. and Davido, D. J. (2009), A flow cytometric assay for the study of E3 ubiquitin ligase activity. Cytometry, 75A: 634–641. doi:10.1002/cyto.a.20738, which has been published in final form at http://doi.org/10.1002/cyto.a.20738. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.BACKGROUND: Current methods for monitoring E3 ubiquitin ligase activity in cell culture or in vivo are limited. As a result, the degradation of cellular targets by many E3 ubiquitin ligases in live cells has not yet been examined. METHODS: A target of an E3 ubiquitin ligase was expressed as a fluorescently labeled protein in cell culture. If the E3 ubiquitin ligase mediates the degradation of a target protein in cell culture, it is expected that the target will show a reduced fluorescence signal by FCM analysis. We initially used the E3 ubiquitin ligase, herpes simplex virus type 1 (HSV-1) infected cell protein 0 (ICP0) and one of its targets, promyelocytic leukemia (PML) protein, to determine the feasibility of our approach. Cells expressing a PML-GFP fusion protein were selected by cell sorting and infected with an adenoviral vector expressing ICP0. RESULTS: In contrast to mock-infected cells, only PML-GFP-expressing cells infected with the ICP0 adenoviral vector led to a significant decrease in the fluorescence signal of PML-GFP when examined by fluorescence microscopy and FCM analysis. CONCLUSIONS: Using HSV-1 ICP0 as a paradigm, it is possible to examine the live activity of an E3 ubiquitin ligase (via one of its targets) in cell culture with FCM analysis

Stakeholder's perceptions of help-seeking behaviour among people with mental health problems in Uganda

<p>Abstract</p> <p>Introduction</p> <p>Mental health facilities in Uganda remain underutilized, despite efforts to decentralize the services. One of the possible explanations for this is the help-seeking behaviours of people with mental health problems. Unfortunately little is known about the factors that influence the help-seeking behaviours. Delays in seeking proper treatment are known to compromise the outcome of the care.</p> <p>Aim</p> <p>To examine the help-seeking behaviours of individuals with mental health problems, and the factors that may influence such behaviours in Uganda.</p> <p>Method</p> <p>Sixty-two interviews and six focus groups were conducted with stakeholders drawn from national and district levels. Thematic analysis of the data was conducted using a framework analysis approach.</p> <p>Results</p> <p>The findings revealed that in some Ugandan communities, help is mostly sought from traditional healers initially, whereas western form of care is usually considered as a last resort. The factors found to influence help-seeking behaviour within the community include: beliefs about the causes of mental illness, the nature of service delivery, accessibility and cost, stigma.</p> <p>Conclusion</p> <p>Increasing the uptake of mental health services requires dedicating more human and financial resources to conventional mental health services. Better understanding of socio-cultural factors that may influence accessibility, engagement and collaboration with traditional healers and conventional practitioners is also urgently required.</p

Sequence specificity incompletely defines the genome-wide occupancy of Myc

BACKGROUND: The Myc-Max heterodimer is a transcription factor that regulates expression of a large number of genes. Genome occupancy of Myc-Max is thought to be driven by Enhancer box (E-box) DNA elements, CACGTG or variants, to which the heterodimer binds in vitro. RESULTS: By analyzing ChIP-Seq datasets, we demonstrate that the positions occupied by Myc-Max across the human genome correlate with the RNA polymerase II, Pol II, transcription machinery significantly better than with E-boxes. Metagene analyses show that in promoter regions, Myc is uniformly positioned about 100 bp upstream of essentially all promoter proximal paused polymerases with Max about 15 bp upstream of Myc. We re-evaluate the DNA binding properties of full length Myc-Max proteins. Electrophoretic mobility shift assay results demonstrate Myc-Max heterodimers display significant sequence preference, but have high affinity for any DNA. Quantification of the relative affinities of Myc-Max for all possible 8-mers using universal protein-binding microarray assays shows that sequences surrounding core 6-mers significantly affect binding. Compared to the in vitro sequence preferences, Myc-Max genomic occupancy measured by ChIP-Seq is largely, although not completely, independent of sequence specificity. CONCLUSIONS: We quantified the affinity of Myc-Max to all possible 8-mers and compared this with the sites of Myc binding across the human genome. Our results indicate that the genomic occupancy of Myc cannot be explained by its intrinsic DNA specificity and suggest that the transcription machinery and associated promoter accessibility play a predominant role in Myc recruitment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0482-3) contains supplementary material, which is available to authorized users

Self-Reported Sleep Apnea and Dementia Risk: Findings from the Prevention of Alzheimer\u27s Disease with Vitamin E and Selenium Trial

OBJECTIVES: To investigate the association between baseline sleep apnea and risk of incident dementia in the Prevention of Alzheimer\u27s Disease with Vitamin E and Selenium (PREADViSE) study and to explore whether the association depends on apolipoprotein E (APOE) ɛ4 allele status. DESIGN: Secondary analysis based on data collected during PREADViSE. SETTING: Participants were assessed at 128 local clinical study sites during the clinical trial phase and later were followed by telephone from a centralized location. PARTICIPANTS: Men enrolled in PREADViSE (without dementia or other active neurological conditions that affect cognition such as major psychiatric disorders, including depression; N = 7,547). MEASUREMENTS: Participants were interviewed at baseline for sleep apnea. The Memory Impairment Screen (MIS) was administered to each participant annually. Subjects who failed this initial screen were tested with secondary screening tests. Medical history and medication use were determined, and the AD8 dementia screening instrument was used. RESULTS: The effect of self-reported sleep apnea on dementia risk depended on APOE ɛ4 status. When the allele was absent, baseline self-reported sleep apnea was associated with a 66% higher risk of developing dementia (95% confidence interval = 2-170%), whereas self-reported sleep apnea conferred no additional risk for participants with an ɛ4 allele. CONCLUSION: Sleep apnea may increase risk of dementia in the absence of APOE ɛ4. This may help inform prevention strategies for dementia or AD in older men with sleep apnea. Registration: PREADViSE is registered at ClinicalTrials.gov: NCT00040378

Cost-benefit analysis of establishing an inferior vena cava filter clinic

PURPOSE:Adverse events associated with retrievable inferior vena cava filters (IVCFs) have generated an increased interest in improving IVCF retrieval rates to improve patient safety and quality care. This study aims to demonstrate the cost-benefit of implementing an IVCF clinic to improve patient care in an institution in the United States.METHODS:An IVCF clinic was established at a single institution in September 2012 and for ten months referring physicians were contacted to facilitate retrieval when appropriate. Additionally, a retrospective review was conducted on filter placements over the eight preclinic months. Cost-benefit analysis was conducted by creating a model, which incorporated the average cost and reimbursement for permanent and retrievable IVCFs.RESULTS:A total of 190 IVCFs (152 retrievable IVCFs and 38 permanent IVCFs) were implanted during the IVCF clinic period. Twenty-nine percent of the retrievable IVCFs were successfully retrieved compared to 10 of 119 retrievable IVCFs placed during the preclinic period (8.4%). Cost-benefit analysis, using the average of the institution’s six most common reimbursement schedules, demonstrated an average net financial loss per permanent or retrievable IVCF not removed. However, a net financial gain was realized for each retrievable IVCF removed. The additional hospital cost to maintain the IVCF clinic was offset by removing an additional 3.1 IVCFs per year.CONCLUSION:An IVCF clinic significantly increases retrieval rates, promotes patient safety, and is economically feasible. Given the adverse event profile of retrievable IVCFs, strategic efforts such as these ultimately can improve quality care for patients with in-dwelling IVCFs