Medical student attitudes to mental health and psychiatry: the use of a patient-experience short film

Background: Medical student attitudes to mental illness are significantly influenced by their undergraduate educational experience. Medical education therefore has a key role to play in challenging the stigma associated with mental illness. We developed a short educational film aimed at challenging stigmatising attitudes to mental illness and explored its effects on undergraduate medical student attitudes. We hypothesised that levels of stigmatising attitudes in medical students would reduce after students viewed the educational film. Method: We used a validated scale (Mental Illness: Clinician Attitudes, MICA) to examine undergraduate medical student attitudes to mental illness at two time points - prior to (T1) and following (T2) viewing the short film. The film focused on patient experiences and was designed to highlight personal experiences of mental illness. Results: 92 students completed the MICA before the film and 73 students at both time points. Having a personal history of mental illness was associated with less stigmatising attitudes (t=2.4, df=87, p=0.019). Stigma scores were reduced following the film viewing (t=7.101, df=72, p<0.001). Discussion: This study suggests that patient experience films, used as educational tools, can challenge student perceptions of mental illness and lead to a reduction in stigmatising attitudes, at least in the short term. Future studies are required to examine the longer-term effects of such educational interventions in terms of student perceptions and attitudes towards mental health and psychiatry

Fast and Expressive Gesture Recognition using a Combination-Homomorphic Electromyogram Encoder

We study the task of gesture recognition from electromyography (EMG), with the goal of enabling expressive human-computer interaction at high accuracy, while minimizing the time required for new subjects to provide calibration data. To fulfill these goals, we define combination gestures consisting of a direction component and a modifier component. New subjects only demonstrate the single component gestures and we seek to extrapolate from these to all possible single or combination gestures. We extrapolate to unseen combination gestures by combining the feature vectors of real single gestures to produce synthetic training data. This strategy allows us to provide a large and flexible gesture vocabulary, while not requiring new subjects to demonstrate combinatorially many example gestures. We pre-train an encoder and a combination operator using self-supervision, so that we can produce useful synthetic training data for unseen test subjects. To evaluate the proposed method, we collect a real-world EMG dataset, and measure the effect of augmented supervision against two baselines: a partially-supervised model trained with only single gesture data from the unseen subject, and a fully-supervised model trained with real single and real combination gesture data from the unseen subject. We find that the proposed method provides a dramatic improvement over the partially-supervised model, and achieves a useful classification accuracy that in some cases approaches the performance of the fully-supervised model.Comment: 24 pages, 7 figures, 6 tables V2: add link to code, fix bibliograph

Inflammatory adipocyte-derived extracellular vesicles promote leukocyte attachment to vascular endothelial cells

Background and aims. Obesity is associated with an increased risk of cardiovascular disease, but the mechanisms involved are not completely understood. In obesity, the adipocyte microenvironment is characterised by both hypoxia and inflammation. Therefore, we sought to determine whether extracellular vesicles (EVs) derived from adipocytes in this setting might be involved in mediating cardiovascular disease, specifically by promoting leukocyte attachment to vascular endothelial cells. Methods. Mature 3T3-L1 adipocytes were incubated for 24 h under control, TNF-α (30 ng/mL), hypoxia (1% O2), or TNF-α+hypoxia (30 ng/mL, 1% O2) conditions. EVs were isolated by differential ultracentrifugation and analysed by nanoparticle tracking analysis. Primary human umbilical vein endothelial cells (HUVECs) were treated with EVs for 6 h before being lysed for Western blotting to investigate changes in adhesion molecule production, or for use in leukocyte attachment assays. Results. EVs from adipocytes treated with TNF-α and TNF-α+hypoxia increased vascular cell adhesion molecule (VCAM-1) production in HUVECs compared to basal level (4.2 ± 0.6 and 3.8 ± 0.3-fold increase, respectively (p < 0.05)), an effect that was inhibited by an anti-TNF-α neutralising antibody. Production of other adhesion molecules (E-selectin, P-selectin, platelet endothelial cell adhesion molecule and VE-Cadherin) was unchanged. Pre-incubating HUVECs with TNF-α+hypoxia EVs significantly increased leukocyte attachment compared to basal level (3.0 ± 0.4-fold increase (p < 0.05)). Conclusions. Inflammatory adipocyte EVs induce VCAM-1 production in vascular endothelial cells, accompanied by enhanced leukocyte attachment. Preventing adipocyte derived EV-induced VCAM-1 upregulation may offer a novel therapeutic target in the prevention of obesity-driven cardiovascular disease

A scoping review of over-the-counter products for depression, anxiety and insomnia in older people

Background: Depression, anxiety, and insomnia are prevalent in older people and are associated with increased risk of mortality, dependency, falls and reduced quality of life. Prior to or whilst seeking treatment, older people often manage these symptoms or conditions using products purchased over the counter (OTC), such as medication or herbal products. This review aims to map the evidence available for OTC medications, herbal medicines and dietary supplements for depression, anxiety and insomnia in older adults. Methodology: We carried out a scoping review, including searches of five databases to identify relevant randomised controlled trials (inception-Dec 2022). We took an inclusive approach to products to represent the wide range that may be available online. Trials were summarised according to condition and product. Results: We included 47 trials and 10 ongoing trial protocols. Most targeted insomnia (n = 25), followed by depression (n = 20), and mixed conditions (n = 2). None evaluated products targeted at anxiety alone. Where reported, most products appeared to be safe for use, but studies rarely included people with multiple comorbidities or taking concomitant medication. Some types of melatonin for insomnia (n = 19) and omega-3 fatty acids for depression (n = 7) had more substantive evidence compared to the other products. Conclusion: There is a substantial gap in evidence for OTC products for anxiety in older people. This should be addressed in future trials. Research should also focus on products that are widely used, and these need to be tested in older populations that are similar to those who would use them in practice

What over the counter (OTC) products have been evaluated for anxiety in adults aged 18–60? A scoping review

Background Anxiety symptoms and disorders are common in the UK. Whilst waiting for, or alongside, treatments such as anxiolytics or psychological therapies, people often self-manage anxiety symptoms with products purchased over-the-counter (OTC), such as herbal medicines or dietary supplements. However, the evidence for these products is often presented across different reviews and is not easy for patients or healthcare professionals to compare and understand. Aims To determine the nature and size of the evidence base available for these products. Methods A scoping review. CENTRAL, MEDLINE, EMBASE, PsycInfo, and AMED (inception—Dec 2022) were searched for RCTs assessing OTC products in people aged 18–60 with symptoms or a diagnosis of anxiety. Results In total 69 papers assessing a range of products were found, which mostly focussed on kava, lavender, saffron, probiotics, Galphimia glauca and valerian. Studies used varying dosages. Compared to herbal medicine studies, there were much fewer dietary supplement studies and homeopathic remedy studies, despite some of use of these by the general public. Conclusion Future research needs to investigate commonly used but less evaluated products (e.g. chamomile, St John’s Wort) and to evaluate products against or alongside conventional treatments to better reflect patient decision making

A scoping review of over-the-counter products for depression, anxiety and insomnia in older people

Background Depression, anxiety, and insomnia are prevalent in older people and are associated with increased risk of mortality, dependency, falls and reduced quality of life. Prior to or whilst seeking treatment, older people often manage these symptoms or conditions using products purchased over the counter (OTC), such as medication or herbal products. This review aims to map the evidence available for OTC medications, herbal medicines and dietary supplements for depression, anxiety and insomnia in older adults. Methodology We carried out a scoping review, including searches of five databases to identify relevant randomised controlled trials (inception-Dec 2022). We took an inclusive approach to products to represent the wide range that may be available online. Trials were summarised according to condition and product. Results We included 47 trials and 10 ongoing trial protocols. Most targeted insomnia (n = 25), followed by depression (n = 20), and mixed conditions (n = 2). None evaluated products targeted at anxiety alone. Where reported, most products appeared to be safe for use, but studies rarely included people with multiple comorbidities or taking concomitant medication. Some types of melatonin for insomnia (n = 19) and omega-3 fatty acids for depression (n = 7) had more substantive evidence compared to the other products. Conclusion There is a substantial gap in evidence for OTC products for anxiety in older people. This should be addressed in future trials. Research should also focus on products that are widely used, and these need to be tested in older populations that are similar to those who would use them in practice

A scoping review of over-the-counter products for depression, anxiety and insomnia in older people

Background Depression, anxiety, and insomnia are prevalent in older people and are associated with increased risk of mortality, dependency, falls and reduced quality of life. Prior to or whilst seeking treatment, older people often manage these symptoms or conditions using products purchased over the counter (OTC), such as medication or herbal products. This review aims to map the evidence available for OTC medications, herbal medicines and dietary supplements for depression, anxiety and insomnia in older adults. Methodology We carried out a scoping review, including searches of five databases to identify relevant randomised controlled trials (inception-Dec 2022). We took an inclusive approach to products to represent the wide range that may be available online. Trials were summarised according to condition and product. Results We included 47 trials and 10 ongoing trial protocols. Most targeted insomnia (n = 25), followed by depression (n = 20), and mixed conditions (n = 2). None evaluated products targeted at anxiety alone. Where reported, most products appeared to be safe for use, but studies rarely included people with multiple comorbidities or taking concomitant medication. Some types of melatonin for insomnia (n = 19) and omega-3 fatty acids for depression (n = 7) had more substantive evidence compared to the other products. Conclusion There is a substantial gap in evidence for OTC products for anxiety in older people. This should be addressed in future trials. Research should also focus on products that are widely used, and these need to be tested in older populations that are similar to those who would use them in practice

Health State Preference Weights for the Glasgow Outcome Scale Following Traumatic Brain Injury: A Systematic Review and Mapping Study

Background: Valid and relevant estimates of health state preference weights (HSPWs) for Glasgow Outcome Scale (GOS) categories are a key input of economic models evaluating treatments for traumatic brain injury (TBI). Objectives: To characterize existing HSPW estimates, and model the EuroQol five-dimensional questionnaire (EQ-5D) from the GOS, to inform parameterization of future economic models. Methods: A systematic review of HSPWs for GOS categories following TBI was conducted using a highly sensitive search strategy implemented in an extensive range of information sources between 1975 and 2016. A cross-sectional mapping study of GOS health states onto the three-level EQ-5D UK tariff index values was also performed in patients with significant TBI (head region Abbreviated Injury Scale score Z3) from the Victoria State Trauma Registry. A limited dependent variable mixture model was used to estimate the 12-month EQ-5D UK value set as a function of GOS category, age, and other explanatory variables. Results: Six unique HSPWs from five eligible studies were identified. All studies were at high risk of bias with limited applicability. The magnitude of HSPWs differed significantly between studies. Three class mixture models demonstrated excellent goodness of fit to the observed Victoria State Trauma Registry data. GOS category, age at injury, sex, comorbidity, and major extracranial injury all had significant independent effects on mean EQ-5D utility values. Conclusions: The few available HSPWs for GOS categories are challenged by potential biases and restricted generalizability. Mixture models are presented to provide HSPWs for GOS categories consistent with the National Institute for Health and Care Excellence reference cas

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes

HCV Induces Oxidative and ER Stress, and Sensitizes Infected Cells to Apoptosis in SCID/Alb-uPA Mice

Hepatitis C virus (HCV) is a blood-borne pathogen and a major cause of liver disease worldwide. Gene expression profiling was used to characterize the transcriptional response to HCV H77c infection. Evidence is presented for activation of innate antiviral signaling pathways as well as induction of lipid metabolism genes, which may contribute to oxidative stress. We also found that infection of chimeric SCID/Alb-uPA mice by HCV led to signs of hepatocyte damage and apoptosis, which in patients plays a role in activation of stellate cells, recruitment of macrophages, and the subsequent development of fibrosis. Infection of chimeric mice with HCV H77c also led an inflammatory response characterized by infiltration of monocytes and macrophages. There was increased apoptosis in HCV-infected human hepatocytes in H77c-infected mice but not in mice inoculated with a replication incompetent H77c mutant. Moreover, TUNEL reactivity was restricted to HCV-infected hepatocytes, but an increase in FAS expression was not. To gain insight into the factors contributing specific apoptosis of HCV infected cells, immunohistological and confocal microscopy using antibodies for key apoptotic mediators was done. We found that the ER chaperone BiP/GRP78 was increased in HCV-infected cells as was activated BAX, but the activator of ER stress–mediated apoptosis CHOP was not. We found that overall levels of NF-κB and BCL-xL were increased by infection; however, within an infected liver, comparison of infected cells to uninfected cells indicated both NF-κB and BCL-xL were decreased in HCV-infected cells. We conclude that HCV contributes to hepatocyte damage and apoptosis by inducing stress and pro-apoptotic BAX while preventing the induction of anti-apoptotic NF-κB and BCL-xL, thus sensitizing hepatocytes to apoptosis