Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases

Mitochondria contain several flavin-dependent enzymes that can produce reactive oxygen species (ROS). Monitoring ROS release from individual sites in mitochondria is challenging due to unwanted side reactions. We present an easy, inexpensive method for direct assessment of native rates for ROS release using purified flavoenzymes and microplate fluorometry.

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Mental Health-Related Emergency Department Visits Associated with Cannabis in Colorado

Abstract

dsfIntroduction

Cannabis legalization in Colorado resulted in increased cannabis-associated healthcare utilization. Our objective was to examine co-occurrence of cannabis and mental health diagnostic coding in Colorado emergency department (ED) discharges and replicate the study in a subpopulation of ED visits where cannabis involvement and psychiatric diagnosis were confirmed through medical review.

Methods

We collected state-wide ED ICD-9-CM diagnoses from the Colorado Hospital Association and a subpopulation of ED visits from a large, academic hospital from 2012 to 2014. Diagnosis codes identified visits associated with mental health and cannabis. Codes for mental health conditions and cannabis were confirmed by manual records review in the academic hospital subpopulation. Prevalence ratios of mental health ED discharges were calculated to compare cannabis-associated visits to those without cannabis. Rates of mental health and cannabis-associated ED discharges were examined over time.

Results

State-wide data demonstrated a five-fold higher prevalence of mental health diagnoses in cannabis-associated ED visits (PR: 5.35, 95% CI: 5.27-5.43) compared to visits without cannabis. The hospital subpopulation supported this finding with a four-fold higher prevalence of psychiatric complaints in cannabis attributable ED visits (PR: 4.87, 95% CI: 4.36-5.44) compared to visits not attributable to cannabis. State-wide rates of ED visits associated with both cannabis and mental health significantly increased from 2012 to 2014 from 224.5 to 268.4 per 100,000 (p<0.0001).

Conclusions

In Colorado, the prevalence of mental health conditions in ED visits with cannabis-associated diagnostic codes is higher than in those without cannabis. There is a need for further research determining if these findings are truly attributed to cannabis or merely coincident with concurrent increased use and availability.

This article is protected by copyright. All rights reserved.

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UK guidelines on oesophageal dilatation in clinical practice

These are updated guidelines which supersede the original version published in 2004. This work has been endorsed by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG) under the auspices of the oesophageal section of the BSG. The original guidelines have undergone extensive revision by the 16 members of the Guideline Development Group with representation from individuals across all relevant disciplines, including the Heartburn Cancer UK charity, a nursing representative and a patient representative. The methodological rigour and transparency of the guideline development processes were appraised using the revised Appraisal of Guidelines for Research and Evaluation (AGREE II) tool.

Dilatation of the oesophagus is a relatively high-risk intervention, and is required by an increasing range of disease states. Moreover, there is scarcity of evidence in the literature to guide clinicians on how to safely perform this procedure. These guidelines deal specifically with the dilatation procedure using balloon or bougie devices as a primary treatment strategy for non-malignant narrowing of the oesophagus. The use of stents is outside the remit of this paper; however, for cases of dilatation failure, alternative techniques—including stents—will be listed. The guideline is divided into the following subheadings: (1) patient preparation; (2) the dilatation procedure; (3) aftercare and (4) disease-specific considerations. A systematic literature search was performed. The Grading of Recommendations Assessment, Develop­ment and Evaluation (GRADE) tool was used to evaluate the quality of evidence and decide on the strength of recommendations made.

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Direct-acting Antivirals Do Not Increase the Risk of Hepatocellular Carcinoma Recurrence after Local-Regional Therapy or Liver Transplant Waitlist Dropout

ABSTRACT

Whether direct-acting antivirals (DAA) increase the risk of hepatocellular carcinoma (HCC) recurrence after tumor-directed therapy is controversial. We sought to determine the impact of DAA therapy on HCC recurrence after local-regional therapy (LRT) and waitlist dropout among liver transplant (LT) candidates with HCC. We performed a retrospective cohort study of 149 LT candidates with HCV and HCC at a single center from 2014-2016. Cumulative incidence of HCC recurrence post-LRT and waitlist dropout was estimated by DAA group. Factors associated with each outcome were evaluated using competing risks regression. A propensity score stabilized inverse probability weighting approach was used to account for differences in baseline characteristics between groups. The no DAA group (n=87) had more severe cirrhosis and lower rates of complete radiologic tumor response after LRT than those treated with DAA (n=62), but had similar alpha-fetoprotein and tumor burden at listing. Cumulative incidence of HCC recurrence within 1-year of complete response after LRT was 47.0% in the DAA group and 49.8% in the no DAA group (p=0.93). In adjusted competing risk analysis using weighted propensity score modeling, risk of HCC recurrence was similar in the DAA group compared to those without DAA (HR 0.91, 95% CI 0.58-1.42, p=0.67). Patients treated with DAA had lower risk of waitlist dropout due to tumor progression or death compared to the no DAA group in adjusted weighted analysis (HR 0.30, 95% CI 0.13-0.69, p=0.005). Conclusions: In LT candidates with HCV and HCC with initial complete response to LRT, DAA use is not associated with increased risk of HCC recurrence, but rather is associated with reduced risk of waitlist dropout due to tumor progression or death. This article is protected by copyright. All rights reserved.

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Certain BCG-reactive responses are associated with bladder cancer prognosis

Abstract

A subset of bladder patients does not respond to BCG treatment effectively and the underlying reason behind this observation is currently unclear. CD4⁺ T cells are composed of various subsets that each expresses a distinctive set of cytokines and can potently shift the immune response toward various directions. In this study, we examined the CD4⁺ T-cell cytokine response in bladder cancer patients toward BCG stimulation. We found that bladder cancer patients presented a variety of responses toward BCG, with no uniform characteristics. Those patients with high IFN-γ and IL-21 expression in CD4⁺ T cells presented significantly better prognosis than patients with low cytokine secretion in CD4⁺ T cells. Tumor-infiltrating CD4⁺ T cells were significantly less potent in expressing IFN-γ, IL-4, and IL-17, and more potent in expressing IL-10 than circulating CD4⁺ T cells. In addition, we found no difference in CD80, CD86, or MHC II expression by macrophages from patients with different IFN-γ and IL-21 levels. However, the secretion of IL-12, a Th1-skewing cytokine, was released at significantly higher level by macrophages from patients with high IFN-γ or high IL-21 secretion. We also identified that modulating monocytes/macrophages by GM-CSF-mediated polarization resulted in significantly elevated expression of IFN-γ and IL-21 from CD4⁺ T cells. Overall, these results suggested that the specific types of responses mounted by CD4⁺ T cells were critical to the final outcome of bladder cancer patients and can be influenced by monocyte/macrophage polarization.

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Efficacy of slow oscillatory-transcranial direct current stimulation on EEG and memory – contribution of an inter-individual factor

Abstract

Despite many reports on beneficial effects of anodal slow oscillatory-transcranial direct current stimulation (so-tDCS) during non-rapid eye movement (NREM) sleep on memory consolidation, frequent negative outcomes have also been observed. Our working hypothesis is that so-tDCS efficacy is strongly dependent upon the susceptibility of the underlying network. One component determining susceptibility of the network is hypothesized to be reflected in learning or 'task-induced' plastic changes. Another component is hypothesized to represent inter-individual confounds. Twenty five (15 female) healthy students participated in two learning conditions with and without so-tDCS during early nocturnal NREM sleep, and in one control condition without learning tasks. So-tDCS was applied in five 5-minute blocks. EEG was assessed during two time windows: an acute period with five 1-minute epochs after each stimulation block, and a 150-minute post-stimulation time period. Inter-individual differences were assessed by a memory quotient (MQ) and subjects classified into high- versus low-scoring groups. Although so-tDCS was efficient in enhancing fast spindle parameters in the 150-min time period in all subjects, so-tDCS failed to modulate memory consolidation. In contrast, in subjects with a high MQ memory retention on a figural paired-associate task was significantly increased after so-tDCS. Task-induced slow spindle density was modulated in the opposite direction in subjects with high vs. low MQ being increased in the high-MQ group only. Effects of so-tDCS on EEG were limited to fast-spindle modulations in both time windows. These results reveal that inter-individual confound can impact so-tDCS efficacy, suggesting potential use of such factors as biomarkers.

This article is protected by copyright. All rights reserved.

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Targeting strategies of mHealth interventions for maternal health in low and middle-income countries: a systematic review protocol

Introduction

Recently, there has been a steady increase in mobile health (mHealth) interventions aimed at improving maternal health of women in low-income and middle-income countries. While there is evidence indicating that these interventions contribute to improvements in maternal health outcomes, other studies indicate inconclusive results. This uncertainty has raised additional questions, one of which pertains to the role of targeting strategies in implementing mHealth interventions and the focus on pregnant women and health workers as target groups. This review aims to assess who is targeted in different mHealth interventions and the importance of targeting strategies in maternal mHealth interventions.

Methods and analysis

We will search for peer-reviewed, English-language literature published between 1999 and July 2017 in PubMed, Web of Knowledge (Science Direct, EMBASE) and Cochrane Central Registers of Controlled Trials. The study scope is defined by the Population, Intervention, Comparison and Outcomes framework: P, community members with maternal or reproductive needs; I, electronic health or mHealth programmes geared at improving maternal or reproductive health; C, other non-electronic health or mHealth-based interventions; O, maternal health measures including family planning, antenatal care attendance, health facility delivery and postnatal care attendance.

Ethics and dissemination

This study is a review of already published or publicly available data and needs no ethical approval. Review results will be published in a peer-reviewed journal and presented at international conferences.

PROSPERO registration number

CRD42017072280.

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