Green tea extract and its metabolites induce biochemical changes linked to hepatotoxicity in HepG2 cells

Green tea has been consumed for thousands of years and its concentrated extract is now a popular herbal supplement frequently consumed in isolation or as part of a multi-ingredient product. Green tea extract (GTE) is commonly used for its wide range of purported health benefits and, as with most herbal supplements, its sale on the Australian market is regulated by the Therapeutic Goods Administration without requiring pre-market safety or efficacy analysis. Unfortunately, GTE has been implicated in over 50 cases of liver damage in the last 20 years, a number of which resulted in transplantation as the only option for patient survival. Despite the clear link between this supplement and liver injury in these individuals, little is currently known in regards to which biochemical pathways are affected during GTE-induced hepatotoxicity and the extent to which this is mediated by metabolic products of GTE. In this study, GTE and individual catechins were metabolised with S9 human liver fraction and subsequently analysed using untargeted metabolomics. The results confirmed that some metabolism of the GTE had occurred, with the production of at least 17 GTE metabolites. Of these suspected metabolites, 10 were also found in the metabolised catechins, suggesting that more than half of these compounds were metabolites of the catechins in GTE. To assess hepatotoxicity, HepG2 cells were exposed to either unmetabolised or metabolised GTE at doses equivalent to 1 mg/mL. Additionally, to assess the impact of GTE on drug-induced liver injury, another group of cells were exposed to 15 mM paracetamol, 1 mg/mL GTE or a combination of both treatments. The exposure period for all treatments was 24 h, after which small molecule metabolites were extracted from harvested cells and analysed using untargeted metabolomics. Changes were observed in amino acids, carbohydrates and fatty acids in all treatment groups, and the same biochemical pathways appeared to be affected in all GTE treatment variations. Cell treatment with GTE metabolites appeared to yield less cytotoxicity than those treated with unmetabolised GTE. It was unable to be determined whether GTE exacerbated paracetamol-induced hepatotoxicity from the results obtained in this study. Overall, the findings from this study suggested that GTE causes disruption to cellular lipids, proteins, nucleic acids and the mitochondria, potentially as a result of oxidative stress. Given the popularity and ready availability of GTE, regulation of herbal supplements containing this product must be improved to ensure consumer safety and ultimately prevent further cases of liver damage

From Slurs to Science, Racism to Revisionism: White Nationalist Rhetors and Legitimation in the Stormfront Community

While on the surface mainstream discussions about race appear to encompass the values and ideologies associated with egalitarianism, subtle and at times not so subtle discussions continue to disparage groups and individuals who have been historically associated with the minority. The growing existence of hate groups illustrates that arguments for these extreme ideologies are not only present but for some individuals are gaining in acceptance. For this reason, I perform a critical discourse analysis of the language of one of the most popular and prolific White Nationalist groups on the Internet, Stormfront. In particular, I examine how scientific and revisionist discourse is used throughout Stormfront to create a seemingly rational and legitimate justification for White Nationalist ideology. Focusing on scientific and historical discourses, this analysis identifies the similar argument types, orders of discourse, and styles between mainstream and White Nationalist discourse to show how seamlessly Stormfront discourse draws off of mainstream discourse. Designed to divert the audience from the stigma associated with White Nationalism, Stormfront users have intentionally adopted a mainstream script that follows current social norms. This analysis finds that Stormfront members use current scientific research to advance the White Nationalist ideology through the incorporation of a socially acceptable and mainstream discourse that is granted high status. Similarly, Stormfront members recontextualize authoritative historical discourses and mainstream mediated discourse to recast White Nationalists as the victims of inequality under a guise of legitimacy. Furthermore, both the science and revisionist threads on Stormfront use similar techniques (hyperlinking, source referral, etc.) and styles (assertions, legitimizing language, modality, etc.) to advance these arguments. Additionally, both threads incorporate external sources to their discourse, and this interdiscursivity gradually begins to chip away at the boundaries between extremist/hate/racist speech and mainstream discourse. These similar discourses are suggestive of a transition from the “extreme” to a more subtle, indirect racism that may have a more persuasive effect when presented under the guise of the socially acceptable

When things fall apart and when they come together: Tracing the processes of a task-shared intervention for perinatal depression in South Africa

Depression in the perinatal period carries a significant burden of disease and can have negative impacts on foetuses and infants of mothers suffering from the illness. Risk factors for perinatal depression are particularly high in Low- and Middle-Income Countries (LMICs), and include partner abuse, economic insecurity, HIV, unwanted pregnancy, and food insecurity. Despite the substantial burden, there is a considerable 'treatment gap' between the need for treatment and the provision of services for perinatal depression in LMICs. Task sharing using non-specialist health workers has been recommended as a costeffective means to address this treatment gap and reduce the burden on mental health specialists in public health services. Evidence has shown moderate effects of task-shared treatments on the reduction of perinatal depression, but little is known about the processes, mechanisms and elements that lead these treatments to be effective. This thesis is nested within the Africa Focus on Intervention Research for Mental Health - South Africa (AFFIRM-SA) randomised controlled trial (RCT), which aimed to test a task-shared psychological treatment for perinatal depression in Khayelitsha, a low-income township outside of Cape Town in South Africa. The aim of this thesis was to explore the mechanisms of implementation and change of this intervention through a process evaluation. Before implementation of the intervention, qualitative research was employed to explore the idioms, symptoms and perceived causes of depression particular to perinatal women living in Khayelitsha, using semistructured interviews and a framework analysis approach. This was conducted with 12 depressed and nine non-depressed pregnant women and mothers of young babies, and 13 health care providers. These idioms and symptoms were also compared with the ICD 10 and DSM-5 criteria for major depression. The research found that local idioms used to describe depression included 'stress', 'thinking too much', being sad or unhappy, and being scared. Some of the common symptoms of depression were expressed as withdrawal and not wanting to talk, crying or sadness, poor concentration, thinking too much, fear and anxiety, stress, sleep problems, headaches, and body pain. The primary causes that women attributed to these depressive symptoms were lack of support, having an unwanted pregnancy, death of a loved one, poverty, unemployment, thinking too much, coping with a new baby, and stress. These were exacerbated by the extreme risk factors the women faced in Khayelitsha such as low income levels, poverty, partner abuse, low education levels, poor housing and living conditions, and poor health care. The findings from this research were recommended for inclusion in the development of the counselling intervention manual for the RCT. Following implementation of the AFFIRM-SA RCT counselling intervention, the trial outcome assessments found non-significant effects in the reduction of depressive symptoms on the Hamilton Depression Rating scale (HDRS) at three and 12 months post-partum, but also found significant improvements on the Edinburgh Postnatal Depression Scale (EPDS) at both time points for the intervention group, compared to the control group. The process evaluation for this thesis subsequently examined mechanisms and contextual factors that may have influenced the intervention outcome. This involved reviewing the counselling manual and conducting a grounded theory analysis of a sample of the counselling session transcripts from the intervention. The review of the counselling manual found that the structure, layout, instructions and grammar in the manual may have led to some difficulties in its interpretation and use for counsellors and participants. The grounded theory analysis included 39 participants who had completed all six sessions of the intervention (totalling 234 sessions). The use of grounded theory allowed for findings to emerge which had not been prespecified before analysis. This process began with the identification of 'open codes', which was anything that 'stood out' from the data. Following this, a secondary 'axial coding' of the data then identified four themes that encompassed all of the open codes. The themes were: therapeutic breakdowns in the counselling sessions, the adverse influence of socio-economic context on therapeutic effectiveness, reported positive outcomes, and attributes given for the reported changes. In turn, these themes could be represented by one of two 'core concepts' that characterised the processes that occurred during the counselling sessions. These were deviations from the intended counselling protocol (when things fall apart), and effectiveness of the counselling sessions (when things come together). The third level of coding, termed 'selective coding', examined the potential reasons for the deviations from protocol and the mechanisms or elements behind the attributions of the reported outcomes. Possible reasons for deviations include the original context of the development of the intervention, not fully incorporating the formative research and pilot findings, the limited skill base of the counsellors, limited training and supervision, the structure and design of the intervention, ownership by the counsellors of the intervention, the role of advice in this context, and contextually related need from the participants. This also explained potential reasons for the non-significant effects of the intervention on the HDRS. In terms of the attributions that the participants gave for their outcomes of change, many of these acted as 'mechanisms' or therapeutic elements of the counselling, and these elements were similar to previous research on common or 'non-specific' elements in the therapeutic space. These elements played an important role in participants' feelings of connection and reduction of distress, despite evidence of deviations from the counselling protocol. This was in keeping with the significant effects of the intervention on the EPDS outcomes. The thesis presents two models of processes that occurred in the intervention. The first posits that the intervention did not sufficiently disrupt the mechanisms or context that creates and perpetuates depression to enable long term shifts or significant changes in clinical depressive symptoms. The second suggests that the intervention provided a sense of connection and a subsequent 'buffer' of resilience to handle every-day stressors, but that this buffer was short-term and could not provide longer-term resilience against the extreme context of poverty, unemployment, abuse and trauma. Through a process evaluation of the design and implementation of the AFFIRM-SA intervention, this thesis presents a wide range of contextual considerations and therapeutic elements relevant to designing and implementing more acceptable and responsive public mental health interventions that aim to bring about real and sustainable change for perinatal depression in South Africa and other LMICs

Probing the origin of UX Ori-type variability in the YSO binary CO Ori with VLTI/GRAVITY

The primary star in the young stellar object (YSO) binary CO Ori displays UX Ori-type variability: irregular, high amplitude optical and near-infrared photometric fluctuations where flux minima coincide with polarization maxima. This is attributed to changes in local opacity. In CO Ori A, these variations exhibit a 12.4 yr cycle. Here, we investigate the physical origin of the fluctuating opacity and its periodicity using interferometric observations of CO Ori obtained using VLTI/GRAVITY. Continuum K-band circum-primary and circum-secondary emission are marginally spatially resolved for the first time while Br$\gamma$ emission is detected in the spectrum of the secondary. We estimate a spectral type range for CO Ori B of K2-K5 assuming visual extinction, $A_{\rm{V}}=2$ and a distance of 430 pc. From geometric modelling of the continuum visibilities, the circum-primary emission is consistent with a central point source plus a Gaussian component with a full-width-half-maximum of 2.31$\pm$0.04 milliarcseconds (mas), inclined at 30.2$\pm$2.2$^{\circ}$ and with a major axis position angle of 40$\pm$6$^{\circ}$. This inclination is lower than that reported for the discs of other UX Ori-type stars, providing a first indication that the UX Ori phenomena may arise through fluctuations in circumstellar material exterior to a disc, e.g. in a dusty outflow. An additional wide, symmetric Gaussian component is required to fit the visibilities of CO Ori B, signifying a contribution from scattered light. Finally, closure phases of CO Ori A were used to investigate whether the 12.4 yr periodicity is associated with an undetected third component, as has been previously suggested. We rule out any additional companions contributing more than 3.6% to the K-band flux within ~7.3-20 mas of CO Ori A.Comment: 7 pages, 4 figures, accepted for publication in MNRA

Enabling research in care homes : an evaluation of a national network of research ready care homes

© 2014 Davies et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedIn the UK care homes are one of the main providers of long term care for older people with dementia. Despite the recent increase in care home research, residents with dementia are often excluded from studies. Care home research networks have been recommended by the Ministerial Advisory Group on Dementia Research (MAGDR) as a way of increasing research opportunities for residents with dementia. This paper reports on an evaluation of the feasibility and early impact of an initiative to increase care home participation in researchPeer reviewe

Evaluation of the End of Life Care Train the Trainer (TTT) Education Model

Final Published versio