Social problems in oncology

A study was undertaken to describe, evaluate and categorise the social problems experienced by cancer patients. Ninety-six adult cancer patients at all stages of disease participated in either a telephone focus group discussion, a face to face focus group or an individual interview which were tape recorded and transcribed. Six experts analysed the transcripts. A total of 32 social problems were identified categorized under eight headings plus four single items. The categories were: problems with (1) managing in the home, (2) health and welfare services, (3) finances, (4) employment, (5) legal matters, (6) relationships, (7) sexuality and body image and (8) recreation. Problems with relationships and communication were the most frequently reported with financial, employment, body image and domestic problems also being widely endorsed. Female groups, younger patient groups and groups where the aim of treatment was palliative reported more social problems than other groups. Social problems are common and important to cancer patients. The social problems identified in this study will contribute to an item pool generated for developing a Social Problems Inventory that may be included in patient centred assessment as part of routine oncology practice

Retrograde semaphorin-plexin signalling drives homeostatic synaptic plasticity.

Homeostatic signalling systems ensure stable but flexible neural activity and animal behaviour. Presynaptic homeostatic plasticity is a conserved form of neuronal homeostatic signalling that is observed in organisms ranging from Drosophila to human. Defining the underlying molecular mechanisms of neuronal homeostatic signalling will be essential in order to establish clear connections to the causes and progression of neurological disease. During neural development, semaphorin-plexin signalling instructs axon guidance and neuronal morphogenesis. However, semaphorins and plexins are also expressed in the adult brain. Here we show that semaphorin 2b (Sema2b) is a target-derived signal that acts upon presynaptic plexin B (PlexB) receptors to mediate the retrograde, homeostatic control of presynaptic neurotransmitter release at the neuromuscular junction in Drosophila. Further, we show that Sema2b-PlexB signalling regulates presynaptic homeostatic plasticity through the cytoplasmic protein Mical and the oxoreductase-dependent control of presynaptic actin. We propose that semaphorin-plexin signalling is an essential platform for the stabilization of synaptic transmission throughout the developing and mature nervous system. These findings may be relevant to the aetiology and treatment of diverse neurological and psychiatric diseases that are characterized by altered or inappropriate neural function and behaviour

Increasing confidence and changing behaviors in primary care providers engaged in genetic counselling.

BackgroundScreening and counseling for genetic conditions is an increasingly important part of primary care practice, particularly given the paucity of genetic counselors in the United States. However, primary care physicians (PCPs) often have an inadequate understanding of evidence-based screening; communication approaches that encourage shared decision-making; ethical, legal, and social implication (ELSI) issues related to screening for genetic mutations; and the basics of clinical genetics. This study explored whether an interactive, web-based genetics curriculum directed at PCPs in non-academic primary care settings was superior at changing practice knowledge, attitudes, and behaviors when compared to a traditional educational approach, particularly when discussing common genetic conditions.MethodsOne hundred twenty one PCPs in California and Pennsylvania physician practices were randomized to either an Intervention Group (IG) or Control Group (CG). IG physicians completed a 6 h interactive web-based curriculum covering communication skills, basics of genetic testing, risk assessment, ELSI issues and practice behaviors. CG physicians were provided with a traditional approach to Continuing Medical Education (CME) (clinical review articles) offering equivalent information.ResultsPCPs in the Intervention Group showed greater increases in knowledge compared to the Control Group. Intervention PCPs were also more satisfied with the educational materials, and more confident in their genetics knowledge and skills compared to those receiving traditional CME materials. Intervention PCPs felt that the web-based curriculum covered medical management, genetics, and ELSI issues significantly better than did the Control Group, and in comparison with traditional curricula. The Intervention Group felt the online tools offered several advantages, and engaged in better shared decision making with standardized patients, however, there was no difference in behavior change between groups with regard to increases in ELSI discussions between PCPs and patients.ConclusionWhile our intervention was deemed more enjoyable, demonstrated significant factual learning and retention, and increased shared decision making practices, there were few differences in behavior changes around ELSI discussions. Unfortunately, barriers to implementing behavior change in clinical genetics is not unique to our intervention. Perhaps the missing element is that busy physicians need systems-level support to engage in meaningful discussions around genetics issues. The next step in promoting active engagement between doctors and patients may be to put into place the tools needed for PCPs to easily access the materials they need at the point-of-care to engage in joint discussions around clinical genetics

ATG5 is essential for ATG8-dependent autophagy and mitochondrial homeostasis in Leishmania major

Macroautophagy has been shown to be important for the cellular remodelling required for Leishmania differentiation. We now demonstrate that L. major contains a functional ATG12-ATG5 conjugation system, which is required for ATG8-dependent autophagosome formation. Nascent autophagosomes were found commonly associated with the mitochondrion. L. major mutants lacking ATG5 (Δatg5) were viable as promastigotes but were unable to form autophagosomes, had morphological abnormalities including a much reduced flagellum, were less able to differentiate and had greatly reduced virulence to macrophages and mice. Analyses of the lipid metabolome of Δatg5 revealed marked elevation of phosphatidylethanolamines (PE) in comparison to wild type parasites. The Δatg5 mutants also had increased mitochondrial mass but reduced mitochondrial membrane potential and higher levels of reactive oxygen species. These findings indicate that the lack of ATG5 and autophagy leads to perturbation of the phospholipid balance in the mitochondrion, possibly through ablation of membrane use and conjugation of mitochondrial PE to ATG8 for autophagosome biogenesis, resulting in a dysfunctional mitochondrion with impaired oxidative ability and energy generation. The overall result of this is reduced virulence

Genetic nurse counsellors can be an acceptable and cost-effective alternative to clinical geneticists for breast cancer risk genetic counselling. Evidence from two parallel randomised controlled equivalence trials

This study compared genetic nurse counsellors with standard services for breast cancer genetic risk counselling services in two regional genetics centres, in Grampian region, North East Scotland and in Cardiff, Wales. Women referred for genetic counselling were randomised to an initial genetic counselling appointment with either a genetic nurse counsellor (intervention) or a clinical geneticist (current service, control). Participants completed postal questionnaires before, immediately after the counselling episode and 6 months later to assess anxiety, general health status, perceived risk and satisfaction. A parallel economic evaluation explored factors influencing cost-effectiveness. The two concurrent randomised controlled equivalence trials were conducted and analysed separately. In the Grampian trial, 289 patients (193 intervention, 96 control) and in the Wales trial 297 patients (197 intervention and 100 control) returned a baseline questionnaire and attended their appointment. Analysis suggested at least likely equivalence in anxiety (the primary outcome) between the two arms of the trials. The cost per counselling episode was £11.54 less for nurse-based care in the Grampian trial and £12.50 more for nurse-based care in Cardiff. The costs were sensitive to the grade of doctor (notionally) replaced and the extent of consultant supervision required by the nurse. In conclusion, care based on genetic nurse counsellors was not significantly different from conventional cancer genetic services in both trial locations

Gene Expression Changes in GABAA Receptors and Cognition Following Chronic Ketamine Administration in Mice

Ketamine is a well-known anesthetic agent and a drug of abuse. Despite its widespread use and abuse, little is known about its long-term effects on the central nervous system. The present study was designed to evaluate the effect of long-term (1- and 3-month) ketamine administration on learning and memory and associated gene expression levels in the brain. The Morris water maze was used to assess spatial memory and gene expression changes were assayed using Affymetrix Genechips; a focus on the expression of GABAA receptors that mediate a tonic inhibition in the brain, was confirmed by quantitative real-time PCR and western blot. Compared with saline controls, there was a decline in learning and memory performance in the ketamine-treated mice. Genechip results showed that 110 genes were up-regulated and 136 genes were down-regulated. An ontology analysis revealed the most significant effects of ketamine were on GABAA receptors. In particular, there was a significant up-regulation of both mRNA and protein levels of the alpha 5 subunit (Gabra5) of the GABAA receptors in the prefrontal cortex. In conclusion, chronic exposure to ketamine impairs working memory in mice, which may be explained at least partly by up-regulation of Gabra5 subunits in the prefrontal cortex

New ideas for non-animal approaches to predict repeated-dose systemic toxicity: Report from an EPAA Blue Sky Workshop

© 2020 The Authors The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a ‘Blue Sky Workshop’ on new ideas for non-animal approaches to predict repeated-dose systemic toxicity. The aim of the Workshop was to formulate strategic ideas to improve and increase the applicability, implementation and acceptance of modern non-animal methods to determine systemic toxicity. The Workshop concluded that good progress is being made to assess repeated dose toxicity without animals taking advantage of existing knowledge in toxicology, thresholds of toxicological concern, adverse outcome pathways and read-across workflows. These approaches can be supported by New Approach Methodologies (NAMs) utilising modern molecular technologies and computational methods. Recommendations from the Workshop were based around the needs for better chemical safety assessment: how to strengthen the evidence base for decision making; to develop, standardise and harmonise NAMs for human toxicity; and the improvement in the applicability and acceptance of novel techniques. “Disruptive thinking” is required to reconsider chemical legislation, validation of NAMs and the opportunities to move away from reliance on animal tests. Case study practices and data sharing, ensuring reproducibility of NAMs, were viewed as crucial to the improvement of non-animal test approaches for systemic toxicity.U.S.Environmental Protection Agency (EPA); Agency for Science, Technology and Research ( A*STAR), Singapor

Policy challenges for the pediatric rheumatology workforce: Part II. Health care system delivery and workforce supply

The United States pediatric population with chronic health conditions is expanding. Currently, this demographic comprises 12-18% of the American child and youth population. Affected children often receive fragmented, uncoordinated care. Overall, the American health care delivery system produces modest outcomes for this population. Poor, uninsured and minority children may be at increased risk for inferior coordination of services. Further, the United States health care delivery system is primarily organized for the diagnosis and treatment of acute conditions. For pediatric patients with chronic health conditions, the typical acute problem-oriented visit actually serves as a barrier to care. The biomedical model of patient education prevails, characterized by unilateral transfer of medical information. However, the evidence basis for improvement in disease outcomes supports the use of the chronic care model, initially proposed by Dr. Edward Wagner. Six inter-related elements distinguish the success of the chronic care model, which include self-management support and care coordination by a prepared, proactive team

The Effects of NR2 Subunit-Dependent NMDA Receptor Kinetics on Synaptic Transmission and CaMKII Activation

N-Methyl-d-aspartic acid (NMDA) receptors are widely expressed in the brain and are critical for many forms of synaptic plasticity. Subtypes of the NMDA receptor NR2 subunit are differentially expressed during development; in the forebrain, the NR2B receptor is dominant early in development, and later both NR2A and NR2B are expressed. In heterologous expression systems, NR2A-containing receptors open more reliably and show much faster opening and closing kinetics than do NR2B-containing receptors. However, conflicting data, showing similar open probabilities, exist for receptors expressed in neurons. Similarly, studies of synaptic plasticity have produced divergent results, with some showing that only NR2A-containing receptors can drive long-term potentiation and others showing that either subtype is capable of driving potentiation. In order to address these conflicting results as well as open questions about the number and location of functional receptors in the synapse, we constructed a Monte Carlo model of glutamate release, diffusion, and binding to NMDA receptors and of receptor opening and closing as well as a model of the activation of calcium-calmodulin kinase II, an enzyme critical for induction of synaptic plasticity, by NMDA receptor-mediated calcium influx. Our results suggest that the conflicting data concerning receptor open probabilities can be resolved, with NR2A- and NR2B-containing receptors having very different opening probabilities. They also support the conclusion that receptors containing either subtype can drive long-term potentiation. We also are able to estimate the number of functional receptors at a synapse from experimental data. Finally, in our models, the opening of NR2B-containing receptors is highly dependent on the location of the receptor relative to the site of glutamate release whereas the opening of NR2A-containing receptors is not. These results help to clarify the previous findings and suggest future experiments to address open questions concerning NMDA receptor function

Brain Changes in Long-Term Zen Meditators Using Proton Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging: A Controlled Study

Introduction: This work aimed to determine whether 1H magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) are correlated with years of meditation and psychological variables in long-term Zen meditators compared to healthy non-meditator controls. Materials and Methods: Design. Controlled, cross-sectional study. Sample. Meditators were recruited from a Zen Buddhist monastery. The control group was recruited from hospital staff. Meditators were administered questionnaires on anxiety, depression, cognitive impairment and mindfulness. 1H-MRS (1.5 T) of the brain was carried out by exploring four areas: both thalami, both hippocampi, the posterior superior parietal lobule (PSPL) and posterior cingulate gyrus. Predefined areas of the brain were measured for diffusivity (ADC) and fractional anisotropy (FA) by MR-DTI. Results: Myo-inositol (mI) was increased in the posterior cingulate gyrus and Glutamate (Glu), N-acetyl-aspartate (NAA) and N-acetyl-aspartate/Creatine (NAA/Cr) was reduced in the left thalamus in meditators. We found a significant positive correlation between mI in the posterior cingulate and years of meditation (r = 0.518; p = .019). We also found significant negative correlations between Glu (r =20.452; p = .045), NAA (r =20.617; p = .003) and NAA/Cr (r =20.448; P = .047) in the left thalamus and years of meditation. Meditators showed a lower Apparent Diffusion Coefficient (ADC) in the left posterior parietal white matter than did controls, and the ADC was negatively correlated with years of meditation (r =20.4850, p = .0066). Conclusions: The results are consistent with the view that mI, Glu and NAA are the most important altered metabolites. This study provides evidence of subtle abnormalities in neuronal function in regions of the white matter in meditators