ELISA detection of phenazepam, etizolam, pyrazolam, flubromazepam, diclazepam and delorazepam in blood using Immunalysis® benzodiazepine kit

Phenazepam and etizolam were the first uncontrolled benzodiazepines available for sale in the UK. Pyrazolam, flubromazepam and diclazepam are not used medicinally anywhere in the world; they are produced exclusively for the uncontrolled, recreational market. It is important to know whether potentially abused drugs like these can be detected in routine toxicological screening tests. The purpose of this study was to evaluate whether the Immunalysis® Benzodiazepines ELISA kit could detect phenazepam, etizolam, pyrazolam, flubromazepam, diclazepam and its metabolite delorazepam. Their cross-reactivity was assessed by comparing the absorbance of the drug with that of oxazepam, the reference standard. This study found that these uncontrolled benzodiazepines cross-react sufficiently to produce a positive result with the Immunalysis® Benzodiazepine ELISA kit. Cross-reactivity ranged from 79 to 107% for phenazepam, etizolam, pyrazolam, flubromazepam, diclazepam and delorazepam fortified into blood. The results show that it is possible to detect these newer benzodiazepines with traditional forensic toxicology laboratory tools and it is important to include these benzodiazepines in the confirmation tests

A pilot randomised controlled trial of metacognitive therapy for prolonged grief

Objectives: Prolonged grief disorder is associated with significant distress and impairment and thus efforts to improve treatments are essential. The present pilot study tested the efficacy and feasibility of group Metacognitive Grief Therapy (MCGT) designed specifically for prolonged grief symptomatology to reduce the psychological distress and impaired function resulting from bereavement. Design/participants: Twenty-two bereaved adult participants with prolonged grief symptomatology were randomised to a wait-list control (n=10) or an intervention condition (n=12) with a 3-month and 6-month follow-up. The wait-list control group was offered treatment after the post-test assessment. Intervention: Participants attended six group MCGT sessions that ran for 2 hours per week. Outcome measures: A primary outcome measure of prolonged grief symptomatology and secondary outcome measures of depression, anxiety, rumination, metacognitive beliefs and quality of life were taken pretreatment and post-treatment for both groups and at the 3-month and 6-month follow-up for the intervention group. A Generalised Linear Mixed Model was used to assess treatment efficacy. Results: Post-treatment intent-to-treat analyses showed MCGT reduced prolonged grief symptomatology (Cohen's d=1.7), depression (d=1.3), anxiety (d=0.8), stress (d=1.0), rumination (d=0.9) and increased quality of life (d=0.6), and these effects were maintained at the 3-month and 6-month follow-ups. No prepost between-group differences were found in metacognitive beliefs. However, a large significant effect was identified at the 3-month and 6-month follow-ups (d=1.0). Conclusion: The results show promise for the utility of group MCGT for reducing psychological distress and promoting quality of life. Additionally, the results underscore the need for a full randomised controlled trial of group MCGT, which may be an important addition to the treatment armamentarium available to support people with prolonged grief

Does voluntary assisted dying cause public stigma for the bereaved?:A vignette-based experiment

Objective Studies in countries where assisted dying is legal show that bereaved people express concern over the potential for social disapproval and social stigma because of the manner of death. There are indications that voluntary assisted dying is judged as less acceptable if the deceased is younger. A vignette-based experiment was used to determine whether public stigma (i.e., negative emotional reactions and desired social distance) and expected grief symptoms are higher for conjugally bereaved people through voluntary assisted dying (vs. long-term illness), when the deceased is a young adult (vs. older adult). Method A 2 × 2 randomized factorial design was conducted with 164 Australian adults (130 women, 34 men, Mage = 37.69 years). Each participant was randomized online to read one of four vignettes and completed measures of anger, fear, prosocial emotions, desire for social distance, and expectations of grief symptomatology. Results A multivariate analysis of variance (MANOVA) was conducted. Death at a young age (28 years) was significantly associated with stronger negative emotional reactions of fear (η2p = 0.048) and anger (η2p = 0.010). There were no differences in outcomes associated with the mode of death, nor was there an interaction between mode of death and age group. Significance of results Concerns that voluntary assisted dying elicits public stigma appear unfounded. The fact that participants reported significantly higher anger and fear in response to bereaved people experiencing loss at a younger (vs. older) age, irrespective of cause of death, indicates that young people who lose their spouse might benefit from additional support. </p

Session 6 discussion: Innovation in eating patterns

Q: You had data to show that millennials eat out less because millennials want to cook at home. Are there data to show that millennials want to cook at home or do millennials have to cook at home because of debt? Millennials are the first generation to have such large debts, like student loans, so they don't have the option to eat out as much as past generations. R[DL]: But yet millennials are still spending a lot of money on food, specifically in the urban environment. Millennials are aged 20–36 and are in very different places in life but all do have paralyzing student debt. It's a great point but there are factions inside of it. The application is if millennials are cooking less/eating at home less, they have significantly more interest in cooking than their parents did. They find it fun and engaging, and they've come to realize that to access the things they want from a health perspective, that it is required. This is where only 7% of the food industry has shown up to address this. Though the difference, and what I'm predicting, is that as they move from the urban landscape, they will cook and we will see time around a dinner table grow for the first time in three generations. That's the essence of the point

A new approach to physical activity maintenance: Rationale, design, and baseline data from the Keep Active Minnesota trial

<p>Abstract</p> <p>Background</p> <p>Since many individuals who initiate physical activity programs are highly likely to return to a sedentary lifestyle, innovative strategies to efforts to increase the number of physically active older adults who successfully <it>maintain </it>beneficial levels of PA for a substantial length of time are needed.</p> <p>Methods/Design</p> <p>The Keep Active Minnesota Trial is a randomized controlled trial of an interactive phone- and mail-based intervention to help 50–70 year old adults who have recently increased their physical activity level, maintain that activity level over a 24-month period in comparison to usual care. Baseline, 6, 12, and 24 month measurement occurred via phone surveys with kilocalories expended per week in total and moderate-to-vigorous physical activity (CHAMPS Questionnaire) as the primary outcome measures. Secondary outcomes include hypothesized mediators of physical activity change (e.g., physical activity enjoyment, self-efficacy, physical activity self-concept), body mass index, and depression. Seven day accelerometry data were collected on a sub-sample of participants at baseline and 24-month follow-up.</p> <p>Discussion</p> <p>The Keep Active Minnesota study offers an innovative approach to the perennial problem of physical activity relapse; by focusing explicitly on physical activity maintenance, the intervention holds considerable promise for modifying the typical relapse curve. Moreover, if shown to be efficacious, the use of phone- and mail-based intervention delivery offers potential for widespread dissemination.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: NCT00283452.</p

Rocaglates induce gain-of-function alterations to eIF4A and eIF4F

Rocaglates are a diverse family of biologically active molecules that have gained tremendous interest in recent years due to their promising activities in pre-clinical cancer studies. As a result, this family of compounds has been significantly expanded through the development of efficient synthetic schemes. However, it is unknown whether all of the members of the rocaglate family act through similar mechanisms of action. Here, we present a comprehensive study comparing the biological activities of >200 rocaglates to better understand how the presence of different chemical entities influences their biological activities. Through this, we find that most rocaglates preferentially repress the translation of mRNAs containing purine-rich 5' leaders, but certain rocaglates lack this bias in translation repression. We also uncover an aspect of rocaglate mechanism of action in which the pool of translationally active eIF4F is diminished due to the sequestration of the complex onto RNA.P50 GM067041 - NIGMS NIH HHS; R24 GM111625 - NIGMS NIH HHS; R35 GM118173 - NIGMS NIH HHSPublished versio

A re‐evaluation of the Plenus Cold Event, and the links between CO2, temperature, and seawater chemistry during OAE 2

International audienceThe greenhouse world of the mid‐Cretaceous (~94 Ma) was punctuated by an episode of abrupt climatic upheaval: Oceanic Anoxic Event 2 (OAE 2). High‐resolution climate records reveal considerable changes in temperature, carbon cycling, and ocean chemistry during this climatic perturbation. In particular, an interval of cooling has been detected in the English Chalk on the basis of an invasive boreal fauna and bulk oxygen‐isotope excursions registered during the early stages of OAE 2—a phenomenon known as the Plenus Cold Event (PCE), which has tentatively been correlated with climatic shifts worldwide.Here we present new high‐resolution neodymium‐, carbon‐, and oxygen‐isotope data, as well as elemental chromium concentrations and cerium anomalies, from the English Chalk exposed at Dover, UK, which we evaluate in the context of >400 records from across the globe. A negative carbon‐isotope excursion that correlates with the original ‘PCE’ is consistently expressed worldwide, and CO2 proxy records, where available, indicate a rise and subsequent fall in CO2 over the Plenus interval. However, variability in the timing and expression of cooling at different sites suggests that, although sea‐surface paleo‐temperatures may reflect a response to global CO2 change, local processes likely played a dominant role at many sites. Variability in the timing and expression of changes in water‐mass character, and problems in determining the driver of observed proxy changes, suggest that no single simple mechanism can link the carbon cycle to oceanography during the Plenus interval and other factors including upwelling and circulation patterns were locally important. As such, it is proposed that the Plenus carbon‐isotope event is a more reliable stratigraphic marker to identify the Plenus interval, rather than any climatic shifts that may have been overprinted by local effects

The antimicrobial peptide cathelicidin drives development of experimental autoimmune encephalomyelitis in mice by affecting Th17 differentiation

Multiple sclerosis (MS) is a highly prevalent demyelinating autoimmune condition; the mechanisms regulating its severity and progression are unclear. The IL-17-producing Th17 subset of T cells has been widely implicated in MS and in the mouse model, experimental autoimmune encephalomyelitis (EAE). However, the differentiation and regulation of Th17 cells during EAE remain incompletely understood. Although evidence is mounting that the antimicrobial peptide cathelicidin profoundly affects early T cell differentiation, no studies have looked at its role in longer-term T cell responses. Now, we report that cathelicidin drives severe EAE disease. It is released from neutrophils, microglia, and endothelial cells throughout disease; its interaction with T cells potentiates Th17 differentiation in lymph nodes and Th17 to exTh17 plasticity and IFN-γ production in the spinal cord. As a consequence, mice lacking cathelicidin are protected from severe EAE. In addition, we show that cathelicidin is produced by the same cell types in the active brain lesions in human MS disease. We propose that cathelicidin exposure results in highly activated, cytokine-producing T cells, which drive autoimmunity; this is a mechanism through which neutrophils amplify inflammation in the central nervous system

Late Cretaceous Temperature Evolution of the Southern High Latitudes:A TEX₈₆ Perspective

The Late Cretaceous was a greenhouse world, characterized by elevated temperatures and high atmospheric pCO2. Even in the context of an extreme greenhouse climate, existing planktic foraminiferal δ18O data from the Falkland Plateau (paleolatitude of ~55°S) suggest anomalous warmth, with sea‐surface temperatures (SSTs) >30 °C for much of the Late Cretaceous, followed by sudden cooling in the Campanian. Over the last two decades, there has been discussion as to whether these high δ18O‐based SSTs reflect a genuine temperature signal and, if so, whether there was a local temperature anomaly in the South Atlantic or whether the data are representative of zonal paleotemperatures at 55°S. To provide new insights into the degree of ocean warming in the southern high latitudes during the Late Cretaceous (Cenomanian to Campanian), new SST records from the Falkland and Kerguelen Plateaus are presented here using the organic geochemical paleothermometer TetraEther indeX of 86 carbon atoms (TEX86). Overall, the TEX86 data support the δ18O data, indicating extreme and widespread warmth in the middle to high southern latitudes in the Late Cretaceous, with SSTs from 27 to 37 °C. Crucially, the TEX86 data show slow, steady cooling from the Turonian to the Campanian and suggest that temperature gradients during the Campanian did not become as steep as suggested by some planktic foraminiferal data