The epsilon toxin (Etx) from Clostridium perfringens has been identified as a potential trigger of multiple sclerosis, functioning as a pore-forming toxin that selectively targets cells expressing the plasma membrane (PM) myelin and lymphocyte protein (MAL). Previously, we observed that Etx induces the release of intracellular ATP in sensitive cell lines. Here, we aimed to re-examine the mechanism of action of the toxin and investigate the connection between pore formation and ATP release.
View Article and Find Full Text PDFMemory B cells (mBCs) are characterized by their long-term stability, fast reactivation, and capability to rapidly differentiate into antibody-secreting cells (ASCs). However, the role of T cells in the differentiation of mBCs, in contrast to naive B cells, remains to be delineated. We study the role of T cells in mBC responses, using CD40L stimulation and autologous T-B co-cultures.
View Article and Find Full Text PDFToxicology has been an active research field for many decades, with academic, industrial and government involvement. Modern omics and computational approaches are changing the field, from merely disease-specific observational models into target-specific predictive models. Traditionally, toxicology has strong links with other fields such as biology, chemistry, pharmacology and medicine.
View Article and Find Full Text PDFBackground: Health behavior interventions, especially those that promote improved diet and physical activity, are increasingly directed toward cancer survivors given their burgeoning numbers and high risk for comorbidity and functional decline. However, for health behavior interventions to achieve maximal public health impact, sustainability at both the individual and organizational levels is crucial. The current study aimed to assess the individual and organizational sustainability of the Harvest for Health mentored vegetable gardening intervention among cancer survivors.
View Article and Find Full Text PDFAdvanced non-small cell lung cancer (NSCLC) is common, deadly, and associated with impairing anxiety for patients and caregivers who often co-experience similar symptoms that can vary together over time. We aimed to discover themes as to how NSCLC patients and caregivers express and cope with anxiety. Semi-structured interviews of patient-caregiver dyads ( = 21), coded using NVivo Software.
View Article and Find Full Text PDFObjective: Nearly 80% of cancer patients struggle with insomnia, which is associated with decreased heart rate variability (HRV) and quality of life (QOL). The aim of this secondary analysis was to evaluate the possible effects of Brief Behavioral Therapy for Cancer-Related Insomnia (BBT-CI), delivered during chemotherapy visits, on QOL and HRV in patients with breast cancer (BC).
Method: QOL and HRV data were obtained during a pilot clinical trial assessing the feasibility and effects of BBT-CI on insomnia.
Background: This phase II RCT was conducted to determine the feasibility and acceptability of brief behavioral therapy for cancer-related insomnia (BBT-CI) in breast cancer patients undergoing chemotherapy. We also assessed the preliminary effects of BBT-CI on insomnia and circadian rhythm in comparison to a Healthy Eating Education Learning control condition (HEAL).
Methods: Of the 71 participants recruited, 34 were randomised to receive BBT-CI and 37 to receive HEAL.
Epsilon toxin (Etx) from is a pore-forming protein that crosses the blood-brain barrier, binds to myelin, and, hence, has been suggested to be a putative agent for the onset of multiple sclerosis, a demyelinating neuroinflammatory disease. Recently, myelin and lymphocyte (MAL) protein has been identified to be a key protein in the cytotoxic effect of Etx; however, the association of Etx with the immune system remains a central question. Here, we show that Etx selectively recognizes and kills only human cell lines expressing MAL protein through a direct Etx-MAL protein interaction.
View Article and Find Full Text PDFBackground: The current study assessed the feasibility of a mentored home-based vegetable gardening intervention and examined changes in health-related outcomes among breast cancer survivors (BCS).
Methods: BCS were randomized to either a year-long vegetable gardening intervention to begin immediately or a wait-list control. Master Gardeners mentored participants in planning, planting, and maintaining 3 seasonal gardens over the course of 1 year.
Background: Holistic approaches are sought to improve lifestyle behaviors and health of cancer survivors long term.
Objective: Our aim was to explore whether a home-based vegetable gardening intervention is feasible and whether it improves diet and other health-related outcomes among older cancer survivors.
Design: We conducted a feasibility trial in which cancer survivors were randomized to receive a year-long gardening intervention immediately or to a wait-list control arm.
Purpose: Cancer survivors are at greater risk of comorbidities and functional decline due to physiological and psychological stress which can be measured by salivary cortisol. If saliva is used, multiple samples must be collected to accurately quantify long-term stress; however, fingernail (FN) and toenail (TN) clippings offer an opportunity to measure retrospective cortisol levels in a non-invasive manner.
Methods: Three sets of FN and TN clippings were collected at 12-month intervals in conjunction with saliva samples from cancer survivors (n = 109) participating in two clinical trials.
Background: Patients with prostate cancer receiving androgen deprivation therapy (ADT) are at risk of sleep disturbance; however, to the authors' knowledge, the mechanisms by which ADT may affect sleep are not well understood. The current study compared objective and subjective sleep disturbance in ADT recipients and controls and examined whether sleep disturbance in ADT recipients is attributable to the influence of ADT on hot flashes and nocturia.
Methods: Patients with prostate cancer were assessed before or within 1 month after the initiation of ADT as well as 6 months and 12 months later (78 patients).
Nat Rev Drug Discov
December 2017
The sharing of legacy preclinical safety data among pharmaceutical companies and its integration with other information sources offers unprecedented opportunities to improve the early assessment of drug safety. Here, we discuss the experience of the eTOX project, which was established through the Innovative Medicines Initiative to explore this possibility.
View Article and Find Full Text PDFBackground: Cancer survivors suffer from long-term adverse effects that reduce health-related quality of life (QOL) and physical functioning, creating an urgent need to develop effective, durable, and disseminable interventions. Harvest for Health, a home-based vegetable gardening intervention, holds promise for these domains.
Methods: This report describes the methods and recruitment experiences from two randomized controlled feasibility trials that employ a waitlist-controlled design.
Objective: Preliminary studies suggest pesticides may be linked to increased cancer risk. Since most pesticides are lipophilic and stored within adipose tissue, serum levels of organochlorines are affected not only by environmental exposures, but also by factors related to lipid turnover and storage. Our objective was to investigate whether serum organochlorines are influenced by weight loss, body fat distribution, and weight cycling.
View Article and Find Full Text PDFBehavioral medicine training is due for an overhaul given the rapid evolution of the field, including a tight funding climate, changing job prospects, and new research and industry collaborations. The purpose of the present study was to collect responses from trainee and practicing members of a multidisciplinary professional society about their perceptions of behavioral medicine training and their suggestions for changes to training for future behavioral medicine scientists and practitioners. A total of 162 faculty and 110 students (total n = 272) completed a web-based survey on strengths of their current training programs and ideas for changes.
View Article and Find Full Text PDFA first analysis of a database of shared preclinical safety data for 1214 small molecule drugs and drug candidates extracted from 3970 reports donated by thirteen pharmaceutical companies for the eTOX project (www.etoxproject.eu) is presented.
View Article and Find Full Text PDFIntroduction: The objectives of the current study were to compare hospitalized smokers' expectancies for electronic cigarettes (e-cigarettes) against their expectancies for tobacco cigarettes and evaluate relationships between e-cigarette expectancies and intention to use e-cigarettes.
Methods: Analysis of baseline data from a one-year longitudinal observational study. The setting was a tertiary care academic center hospital in the Southeastern U.
The high-quality in vivo preclinical safety data produced by the pharmaceutical industry during drug development, which follows numerous strict guidelines, are mostly not available in the public domain. These safety data are sometimes published as a condensed summary for the few compounds that reach the market, but the majority of studies are never made public and are often difficult to access in an automated way, even sometimes within the owning company itself. It is evident from many academic and industrial examples, that useful data mining and model development requires large and representative data sets and careful curation of the collected data.
View Article and Find Full Text PDFHerpes simplex virus has protean manifestations and is an important cause of morbidity in the immunocompromised host. We report a case of recurrent lymphadenopathy and rash in a patient with chronic lymphocytic leukemia. The elusive clinical diagnosis eventually required core biopsy of a lymph node with immunohistochemistry and confirmation by polymerase chain reaction.
View Article and Find Full Text PDFBackground: our objective was to examine the plasma levels of three biological markers involved in cerebral ischemia (IL-6, glutamate and TNF-alpha) in stroke patients and compare them with two different rat models of focal ischemia (embolic stroke model- ES and permanent middle cerebral artery occlusion ligation model-pMCAO) to evaluate which model is most similar to humans.
Secondary Objectives: 1) to analyze the relationship of these biological markers with the severity, volume and outcome of the brain infarction in humans and the two stroke models; and 2) to study whether the three biomarkers are also increased in response to damage in organs other than the central nervous system, both in humans and in rats.
Methods: Multi-center, prospective, case-control study including acute stroke patients (n=58) and controls (n=19) with acute non-neurological diseases
Main Variables: plasma biomarker levels on admission and at 72 h; stroke severity (NIHSS scale) and clinical severity (APACHE II scale); stroke volume; functional status at 3 months (modified Rankin Scale [mRS] and Barthel index [BI]).
Purpose: Prior research examining the impact of androgen deprivation therapy (ADT) for prostate cancer on cognitive performance has found inconsistent relationships. The purpose of this study was to systematically review the existing literature and determine the effect of ADT on performance across seven cognitive domains using meta-analysis.
Methods: A search of PubMed Medline, PsycINFO, Cochrane Library, and Web of Knowledge/Science databases yielded 157 unique abstracts reviewed by independent pairs of raters.