Hoogsteen base pairs proximal and distal to echinomycin binding sites on DNA

Forms of the DNA double helix containing non-Watson-Crick base-pairing have been discovered recently based on x-ray diffraction analysis of quinoxaline antibiotic-oligonucleotide complexes. In an effort to find evidence for Hoogsteen base-pairing at quinoxaline-binding sites in solution, chemical "footprinting" (differential cleavage reactivity) of echinomycin bound to DNA restriction fragments was examined. We report that purines (A>G) in the first and/or fourth base-pair positions of occupied echinomycin-binding sites are hyperreactive to diethyl pyrocarbonate. The correspondence of the solid-state data and the sites of diethyl pyrocarbonate hyperreactivity suggests that diethyl pyrocarbonate may be a sensitive reagent for the detection of Hoogsteen base-pairing in solution. Moreover, a 12-base-pair segment of alternating A-T DNA, which is 6 base pairs away from the nearest strong echinomycin-binding site, is also hyperreactive to diethyl pyrocarbonate in the presence of echinomycin. This hyperreactive segment may be an altered form of right-handed DNA that is entirely Hoogsteen base-paired

Evaluation of carotenoids, polyphenols content and antioxidant activity in the sea buckthorn fruit

Due to the content of biologically active substances, sea buckthorn (Hippophae rhamnoides L.) has become the object of great interest of both, experts and the general public. It is appreciated particularly for the high content of vitamins and other biologically active substances, not only in berries but also in leaves and bark. The aim of the study was to evaluate the nutritional quality of sea buckthorn juice prepared from different varieties of sea buckthorn based on the content of total carotenoids, polyphenols and antioxidant activity. In this study we used varieties Hergo, Tytti, Vitaminaja, Raisa, Askola, Dorana, Slovan, Leikora, Bojan, Terhi and Masličnaja. Content of different components was quantified using spectrophotometry. The total carotenoids content expressed as β-carotene content in juice ranged from 50.63 mg.100 g-1 DM to 93.63 mg.100 g-1 DM, the highest content was in variety Askola and the lowest one in Terhi. Total polyphenols content determined by Folin-Ciocalteu method ranged from 13.03 mg GAE. dm-3 DM to 25.35 mg GAE. dm-3 DM. The highest content was identified in juice of variety Dorana and the lowest one in Raisa. The antioxidant activity quantified by the FOMO method ranges from 45.11 g AA. dm-3 DM to 108.77 g AA. dm-3 DM. The highest antioxidant activity was determined in juice of Dorana and the lowest in variety Boja

Implementing measurement-based care (iMBC) for depression in community mental health: a dynamic cluster randomized trial study protocol

BACKGROUND: Measurement-based care is an evidence-based practice for depression that efficiently identifies treatment non-responders and those who might otherwise deteriorate [1]. However, measurement-based care is underutilized in community mental health with data suggesting fewer than 20 % of behavioral health providers using this practice to inform treatment. It remains unclear whether standardized or tailored approaches to implementation are needed to optimize measurement-based care fidelity and penetration. Moreover, there is some suggestion that prospectively tailored interventions that are designed to fit the dynamic context may optimize public health impact, though no randomized trials have yet tested this notion [2]. This study will address the following three aims: (1) To compare the effect of standardized versus tailored MBC implementation on clinician-level and client-level outcomes; (2) To identify contextual mediators of MBC fidelity; and (3) To explore the impact of MBC fidelity on client outcomes. METHODS/DESIGN: This study is a dynamic cluster randomized trial of standardized versus tailored measurement-based care implementation in Centerstone, the largest provider of community-based mental health services in the USA. This prospective, mixed methods implementation-effectiveness hybrid design allows for evaluation of the two conditions on both clinician-level (e.g., MBC fidelity) and client-level (depression symptom change) outcomes. Central to this investigation is the focus on identifying contextual factors (e.g., attitudes, resources, process, etc.) that mediate MBC fidelity and optimize client outcomes. DISCUSSION: This study will contribute generalizable and practical strategies for implementing systematic symptom monitoring to inform and enhance behavioral healthcare. TRIAL REGISTRATION: Clinicaltrials.gov NCT02266134

The Advice of the Ad-Hoc Working Group on Sampling and Monitoring to the Standing Committee on Drinking Water Concerning Sampling and Monitoring for the Revision of the Council Directive 98/83/EC

The scope of the Ad-Hoc Working Group on Sampling and Monitoring is to give advice on selection of sampling points, sample protocols and sample frequencies in the framework of the revision of the Council Directive 98/83/EC on the quality of water intended for human consumption (Drinking Water Directive). This group was installed by the Standing Committee on Drinking Water on 8 May 2007.JRC.I.5-Physical and chemical exposure

MRI-localized biopsies reveal subtype-specific differences in molecular and cellular composition at the margins of glioblastoma

Glioblastomas (GBMs) diffusely infiltrate the brain, making complete removal by surgical resection impossible. The mixture of neoplastic and nonneoplastic cells that remain after surgery form the biological context for adjuvant therapeutic intervention and recurrence. We performed RNA-sequencing (RNA-seq) and histological analysis on radiographically guided biopsies taken from different regions of GBM and showed that the tissue contained within the contrast-enhancing (CE) core of tumors have different cellular and molecular compositions compared with tissue from the nonenhancing (NE) margins of tumors. Comparisons with the The Cancer Genome Atlas dataset showed that the samples from CE regions resembled the proneural, classical, or mesenchymal subtypes of GBM, whereas the samples from the NE regions predominantly resembled the neural subtype. Computational deconvolution of the RNA-seq data revealed that contributions from nonneoplastic brain cells significantly influence the expression pattern in the NE samples. Gene ontology analysis showed that the cell type-specific expression patterns were functionally distinct and highly enriched in genes associated with the corresponding cell phenotypes. Comparing the RNA-seq data from the GBM samples to that of nonneoplastic brain revealed that the differentially expressed genes are distributed across multiple cell types. Notably, the patterns of cell type-specific alterations varied between the different GBM subtypes: the NE regions of proneural tumors were enriched in oligodendrocyte progenitor genes, whereas the NE regions of mesenchymal GBM were enriched in astrocytic and microglial genes. These subtypespecific patterns provide new insights into molecular and cellular composition of the infiltrative margins of GBM

Diabetes-related foot disease in Australia: a systematic review of the prevalence and incidence of risk factors, disease and amputation in Australian populations

Background Diabetes-related foot disease (DFD) is a leading cause of global hospitalisation, amputation and disability burdens; yet, the epidemiology of the DFD burden is unclear in Australia. We aimed to systematically review the literature reporting the prevalence and incidence of risk factors for DFD (e.g. neuropathy, peripheral artery disease), of DFD (ulcers and infection), and of diabetes-related amputation (total, minor and major amputation) in Australian populations. Methods We systematically searched PubMed and EMBASE databases for peer-reviewed articles published until December 31, 2019. We used search strings combining key terms for prevalence or incidence, DFD or amputation, and Australia. Search results were independently screened for eligibility by two investigators. Publications that reported prevalence or incidence of outcomes of interest in geographically defined Australian populations were eligible for inclusion. Included studies were independently assessed for methodological quality and key data were extracted by two investigators. Results Twenty publications met eligibility and were included. There was high heterogeneity for populations investigated and methods used to identify outcomes. We found within diabetes populations, the prevalence of risk factors ranged from 10.0–58.8%, of DFD from 1.2–1.5%, and the incidence of diabetes-related amputation ranged from 5.2–7.2 per 1000 person-years. Additionally, the incidence of DFD-related hospitalisation ranged from 5.2–36.6 per 1000 person-years within diabetes populations. Furthermore, within inpatients with diabetes, we found the prevalence of risk factors ranged from 35.3–43.3%, DFD from 7.0–15.1% and amputation during hospitalisation from 1.4–5.8%. Conclusions Our review suggests a similar risk factor prevalence, low but uncertain DFD prevalence, and high DFD-related hospitalisation and amputation incidence in Australia compared to international populations. These findings may suggest that a low proportion of people with risk factors develop DFD, however, it is also possible that there is an underestimation of DFD prevalence in Australia in the few limited studies, given the high incidence of hospitalisation and amputation because of DFD. Either way, studies of nationally representative populations using valid outcome measures are needed to verify these DFD-related findings and interpretations

Implementation of the CALM intervention for anxiety disorders: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Investigators recently tested the effectiveness of a collaborative-care intervention for anxiety disorders: Coordinated Anxiety Learning and Management(CALM) []) in 17 primary care clinics around the United States. Investigators also conducted a qualitative process evaluation. Key research questions were as follows: (1) What were the facilitators/barriers to implementing CALM? (2) What were the facilitators/barriers to sustaining CALM after the study was completed?</p> <p>Methods</p> <p>Key informant interviews were conducted with 47 clinic staff members (18 primary care providers, 13 nurses, 8 clinic administrators, and 8 clinic staff) and 14 study-trained anxiety clinical specialists (ACSs) who coordinated the collaborative care and provided cognitive behavioral therapy. The interviews were semistructured and conducted by phone. Data were content analyzed with line-by-line analyses leading to the development and refinement of themes.</p> <p>Results</p> <p>Similar themes emerged across stakeholders. Important facilitators to implementation included the perception of "low burden" to implement, provider satisfaction with the intervention, and frequent provider interaction with ACSs. Barriers to implementation included variable provider interest in mental health, high rates of part-time providers in clinics, and high social stressors of lower socioeconomic-status patients interfering with adherence. Key sustainability facilitators were if a clinic had already incorporated collaborative care for another disorder and presence of onsite mental health staff. The main barrier to sustainability was funding for the ACS.</p> <p>Conclusions</p> <p>The CALM intervention was relatively easy to incorporate during the effectiveness trial, and satisfaction was generally high. Numerous implementation and sustainability barriers could limit the reach and impact of widespread adoption. Findings should be interpreted with the knowledge that the ACSs in this study were provided and trained by the study. Future research should explore uptake of CALM and similar interventions without the aid of an effectiveness trial.</p

Precision electron flow measurements in a disk transmission line.

An analytic model for electron flow in a system driving a fixed inductive load is described and evaluated with particle in cell simulations. The simple model allows determining the impedance profile for a magnetically insulated transmission line given the minimum gap desired, and the lumped inductance inside the transition to the minimum gap. The model allows specifying the relative electron flow along the power flow direction, including cases where the fractional electron flow decreases in the power flow direction. The electrons are able to return to the cathode because they gain energy from the temporally rising magnetic field. The simulations were done with small cell size to reduce numerical heating. An experiment to compare electron flow to the simulations was done. The measured electron flow is {approx}33% of the value from the simulations. The discrepancy is assumed to be due to a reversed electric field at the cathode because of the inductive load and falling electron drift velocity in the power flow direction. The simulations constrain the cathode electric field to zero, which gives the highest possible electron flow

Patient-Specific Metrics of Invasiveness Reveal Significant Prognostic Benefit of Resection in a Predictable Subset of Gliomas

Object Malignant gliomas are incurable, primary brain neoplasms noted for their potential to extensively invade brain parenchyma. Current methods of clinical imaging do not elucidate the full extent of brain invasion, making it difficult to predict which, if any, patients are likely to benefit from gross total resection. Our goal was to apply a mathematical modeling approach to estimate the overall tumor invasiveness on a patient-by-patient basis and determine whether gross total resection would improve survival in patients with relatively less invasive gliomas. Methods In 243 patients presenting with contrast-enhancing gliomas, estimates of the relative invasiveness of each patient's tumor, in terms of the ratio of net proliferation rate of the glioma cells to their net dispersal rate, were derived by applying a patient-specific mathematical model to routine pretreatment MR imaging. The effect of varying degrees of extent of resection on overall survival was assessed for cohorts of patients grouped by tumor invasiveness. Results We demonstrate that patients with more diffuse tumors showed no survival benefit (P = 0.532) from gross total resection over subtotal/biopsy, while those with nodular (less diffuse) tumors showed a significant benefit (P = 0.00142) with a striking median survival benefit of over eight months compared to sub-totally resected tumors in the same cohort (an 80% improvement in survival time for GTR only seen for nodular tumors). Conclusions These results suggest that our patient-specific, model-based estimates of tumor invasiveness have clinical utility in surgical decision making. Quantification of relative invasiveness assessed from routinely obtained pre-operative imaging provides a practical predictor of the benefit of gross total resection