Proper distance in the age of social distancing: Hepatitis C treatment, telehealth and questions of care and responsibility.

During the COVID-19 pandemic, telehealth has played a prominent role in the treatment of hepatitis C. As part of a qualitative study on the accessibility and effectiveness of telehealth for hepatitis C treatment during this period in Australia, this article considers how health-care practitioners and patients experience and manage their proximity to each other in telehealth encounters of care. Comparisons between telehealth and in-person health-care tend to focus on measures of patient satisfaction rather than qualitative changes in treatment relationships. Media scholar Silverstone (Digital media revisited: Theoretical and conceptual innovations in digital domains, MIT Press, 2003) uses the term 'proper distance' to theorise how ethical relationships are mediated by technology. Drawing on this concept, we explore how patients and health-care practitioners understand telehealth as affecting distance and proximity. We find that both groups express some ambivalence about the impact of telehealth on relationships, on the one hand expecting and privileging simple, transactional relationships, and on the other hand, expressing concerns about the loss of more intimate relationships in health care and about 'missing something' while providing health care. Given that proximity is important to the development of ethical relationships in health care, we conclude with some considerations for establishing and sustaining attentive and responsive relationships in telehealth.

'It's a different way to do medicine': Exploring the affordances of telehealth for hepatitis C healthcare.

While the use of telehealth was common in hepatitis C healthcare in Australia in remote and regional areas prior to the COVID-19 pandemic, it has been used more broadly to improve access to hepatitis C heathcare during the pandemic. Despite its widespread uptake, little research has explored how telehealth shapes hepatitis C healthcare. In this article, we draw on the concept of affordances (Latour, 2002) and interviews with 25 healthcare practitioners to explore the emergent possibilities for hepatitis C care that take shape through telehealth. Despite suggestions that telehealth is comparable to in-person care, healthcare practitioners' accounts suggest that telehealth significantly changes the nature of their experience of providing healthcare for hepatitis C. According to these service practitioners, while it increased access to hepatitis C healthcare during the pandemic, it also afforded narrower, less personal healthcare encounters, with a focus on simple and singular issues, and reduced opportunities for communication and rapport. These affordances also discouraged the use of interpreters and by extension the inclusion of patients from non-English speaking backgrounds. However, the data collected also suggest that telehealth has the potential to afford more informal and relaxed healthcare environments and dispositions between healthcare practitioners and patients, potentially disrupting classic practitioner-patient power dynamics. In concluding, the article considers how telehealth models of care might better afford quality hepatitis C healthcare and care beyond COVID-19 pandemic conditions.

The Social and Emotional Impact of Involving Individuals With Mental Illness in the Research Process.

There is a need to involve individuals with a lived experience in health and medical research. Some organizations have developed mechanisms to seek the input of people with a lived experience. However, there are few examples of qualitative research into the impacts of participation. In this study, we investigate the social and emotional impact of participation on individuals, as well as the perceived impact on the organization, in an advisory panel at an Australian mental health research institute. In-depth qualitative interviews were conducted with 50% of the participants on the panel to understand how they conceptualized their involvement. Participants became invested in the organization and their role within it, and found it personally valuable to access diverse perspectives and discuss mental health outside a treatment context. These findings suggest that participating in the research process is beneficial to individuals with a lived experience of mental illness.

Using Mobile Phone Sensor Technology for Mental Health Research: Integrated Analysis to Identify Hidden Challenges and Potential Solutions.

BACKGROUND: Mobile phone sensor technology has great potential in providing behavioral markers of mental health. However, this promise has not yet been brought to fruition. OBJECTIVE: The objective of our study was to examine challenges involved in developing an app to extract behavioral markers of mental health from passive sensor data. METHODS: Both technical challenges and acceptability of passive data collection for mental health research were assessed based on literature review and results obtained from a feasibility study. Socialise, a mobile phone app developed at the Black Dog Institute, was used to collect sensor data (Bluetooth, location, and battery status) and investigate views and experiences of a group of people with lived experience of mental health challenges (N=32). RESULTS: On average, sensor data were obtained for 55% (Android) and 45% (iOS) of scheduled scans. Battery life was reduced from 21.3 hours to 18.8 hours when scanning every 5 minutes with a reduction of 2.5 hours or 12%. Despite this relatively small reduction, most participants reported that the app had a noticeable effect on their battery life. In addition to battery life, the purpose of data collection, trust in the organization that collects data, and perceived impact on privacy were identified as main factors for acceptability. CONCLUSIONS: Based on the findings of the feasibility study and literature review, we recommend a commitment to open science and transparent reporting and stronger partnerships and communication with users. Sensing technology has the potential to greatly enhance the delivery and impact of mental health care. Realizing this requires all aspects of mobile phone sensor technology to be rigorously assessed.

Issues for eHealth in Psychiatry: Results of an Expert Survey.

BACKGROUND: Technology has changed the landscape in which psychiatry operates. Effective, evidence-based treatments for mental health care are now available at the fingertips of anyone with Internet access. However, technological solutions for mental health are not necessarily sought by consumers nor recommended by clinicians. OBJECTIVE: The objectives of this study are to identify and discuss the barriers to introducing eHealth technology-supported interventions within mental health. METHODS: An interactive polling tool was used to ask "In this brave new world, what are the key issues that need to be addressed to improve mental health (using technology)?" Respondents were the multidisciplinary attendees of the "Humans and Machines: A Quest for Better Mental Health" conference, held in Sydney, Australia, in 2016. Responses were categorized into 10 key issues using team-based qualitative analysis. RESULTS: A total of 155 responses to the question were received from 66 audience members. Responses were categorized into 10 issues and ordered by importance: access to care, integration and collaboration, education and awareness, mental health stigma, data privacy, trust, understanding and assessment of mental health, government and policy, optimal design, and engagement. In this paper, each of the 10 issues are outlined, and potential solutions are discussed. Many of the issues were interrelated, having implications for other key areas identified. CONCLUSIONS: As many of the issues identified directly related to barriers to care, priority should be given to addressing these issues that are common across mental health delivery. Despite new challenges raised by technology, technology-supported mental health interventions represent a tremendous opportunity to address in a timely way these major concerns and improve the receipt of effective, evidence-based therapy by those in need.

Patient-derived Mammosphere and Xenograft Tumour Initiation Correlates with Progression to Metastasis.

Breast cancer specific mortality results from tumour cell dissemination and metastatic colonisation. Identification of the cells and processes responsible for metastasis will enable better prevention and control of metastatic disease, thus reducing relapse and mortality. To better understand these processes, we prospectively collected 307 patient-derived breast cancer samples (n = 195 early breast cancers (EBC) and n = 112 metastatic samples (MBC)). We assessed colony-forming activity in vitro by growing isolated cells in both primary (formation) and secondary (self-renewal) mammosphere culture, and tumour initiating activity in vivo through subcutaneous transplantation of fragments or cells into mice. Metastatic samples formed primary mammosphere colonies significantly more frequently than early breast cancers and had significantly higher primary mammosphere colony formation efficiency (0.9 % vs. 0.6 %; p < 0.0001). Tumour initiation in vivo was significantly higher in metastatic than early breast cancer samples (63 % vs. 38 %, p = 0.04). Of 144 breast cancer samples implanted in vivo, we established 20 stable patient-derived xenograft (PDX) models at passage 2 or greater. Lung metastases were detected in mice from 14 PDX models. Mammosphere colony formation in vitro significantly correlated with the ability of a tumour to metastasise to the lungs in vivo (p = 0.05), but not with subcutaneous tumour initiation. In summary, the breast cancer stem cell activities of colony formation and tumour initiation are increased in metastatic compared to early samples, and predict metastasis in vivo. These results suggest that breast stem cell activity will predict for poor outcome tumours, and therapy targeting this activity will improve outcomes for patients with metastatic disease.

The intelligent anatomy spotter: A new approach to incorporate higher levels of Bloom's taxonomy.

The spotter test is an assessment that has been used widely to test practical knowledge of anatomy. Traditional spotter formats often focus solely on knowledge recall, in addition to being an onerous marking burden on staff where consistency in marking free text responses can be questioned. First-year optometry students at the University of Manchester study the functional anatomy of the eye in the first semester of their first year. Included in the assessment of this unit is a spotter examination worth 45% of the total unit mark. Due to the factors listed above, a new spotter format was designed. Students had to answer three questions per specimen where the answers to the questions were the labeled structures themselves (A, B, C, or D). They had to work out the answer to the question and then work out which of the labeled structures was the correct structure, negating the "cueing effect" of standard multiple choice questions. Examination results were analyzed over a six-year period (control groups 2008/2009, 2009/2010, 2010/2011; treatment groups 2011/2012, 2012/2013, 2013/2014). There were no significant differences between marks obtained for the new spotter format when compared with the traditional format. The new format spotter tested comprehension rather than just knowledge, and facilitated marking because subjectiveness was erased, and less time was spent determining whether an answer was correct or not. Anat Sci Educ 9: 440-445. © 2015 American Association of Anatomists.

A detailed mammosphere assay protocol for the quantification of breast stem cell activity.

Since the discovery that neural tissue contains a population of stem cells that form neurospheres in vitro, sphere-forming assays have been adapted for use with a number of different tissue types for the quantification of stem cell activity and self-renewal. One tissue type widely used for stem cell investigations is mammary tissue, and the mammosphere assay has been used in both normal tissue and cancer. Although it is a relatively simple assay to learn, it can be difficult to master. There are methodological and analytical aspects to the assay which require careful consideration when interpreting the results. We describe here a detailed mammosphere assay protocol for the assessment of stem cell activity and self-renewal, and discuss how data generated by the assay can be analysed and interpreted.

Selenium-dependent biogenesis of formate dehydrogenase in Campylobacter jejuni is controlled by the fdhTU accessory genes.

The food-borne bacterial pathogen Campylobacter jejuni efficiently utilizes organic acids such as lactate and formate for energy production. Formate is rapidly metabolized via the activity of the multisubunit formate dehydrogenase (FDH) enzyme, of which the FdhA subunit is predicted to contain a selenocysteine (SeC) amino acid. In this study we investigated the function of the cj1500 and cj1501 genes of C. jejuni, demonstrate that they are involved in selenium-controlled production of FDH, and propose the names fdhT and fdhU, respectively. Insertional inactivation of fdhT or fdhU in C. jejuni resulted in the absence of FdhA and FdhB protein expression, reduced fdhABC RNA levels, the absence of FDH enzyme activity, and the lack of formate utilization, as assessed by (1)H nuclear magnetic resonance. The fdhABC genes are transcribed from a single promoter located two genes upstream of fdhA, and the decrease in fdhABC RNA levels in the fdhU mutant is mediated at the posttranscriptional level. FDH activity and the ability to utilize formate were restored by genetic complementation with fdhU and by supplementation of the growth media with selenium dioxide. Disruption of SeC synthesis by inactivation of the selA and selB genes also resulted in the absence of FDH activity, which could not be restored by selenium supplementation. Comparative genomic analysis suggests a link between the presence of selA and fdhTU orthologs and the predicted presence of SeC in FdhA. The fdhTU genes encode accessory proteins required for FDH expression and activity in C. jejuni, possibly by contributing to acquisition or utilization of selenium.

Evolution and multifarious horizontal transfer of an alternative biosynthetic pathway for the alternative polyamine sym-homospermidine.

Polyamines are small flexible organic polycations found in almost all cells. They likely existed in the last universal common ancestor of all extant life, and yet relatively little is understood about their biological function, especially in bacteria and archaea. Unlike eukaryotes, where the predominant polyamine is spermidine, bacteria may contain instead an alternative polyamine, sym-homospermidine. We demonstrate that homospermidine synthase (HSS) has evolved vertically, primarily in the alpha-Proteobacteria, but enzymatically active, diverse HSS orthologues have spread by horizontal gene transfer to other bacteria, bacteriophage, archaea, eukaryotes, and viruses. By expressing diverse HSS orthologues in Escherichia coli, we demonstrate in vivo the production of co-products diaminopropane and N(1)-aminobutylcadaverine, in addition to sym-homospermidine. We show that sym-homospermidine is required for normal growth of the alpha-proteobacterium Rhizobium leguminosarum. However, sym-homospermidine can be replaced, for growth restoration, by the structural analogues spermidine and sym-norspermidine, suggesting that the symmetrical or unsymmetrical form and carbon backbone length are not critical for polyamine function in growth. We found that the HSS enzyme evolved from the alternative spermidine biosynthetic pathway enzyme carboxyspermidine dehydrogenase. The structure of HSS is related to lysine metabolic enzymes, and HSS and carboxyspermidine dehydrogenase evolved from the aspartate family of pathways. Finally, we show that other bacterial phyla such as Cyanobacteria and some alpha-Proteobacteria synthesize sym-homospermidine by an HSS-independent pathway, very probably based on deoxyhypusine synthase orthologues, similar to the alternative homospermidine synthase found in some plants. Thus, bacteria can contain alternative biosynthetic pathways for both spermidine and sym-norspermidine and distinct alternative pathways for sym-homospermidine.

Hyperbaric oxygen treatment induces platelet aggregation and protein release, without altering expression of activation molecules.

OBJECTIVES: To investigate the effect of hyperbaric oxygen (HBO) on platelet physiology. DESIGN AND METHODS: Human platelets were exposed to HBO (97.7% O(2), balance CO(2) at 2.2 ata) or control (CON; 5% CO(2), balance air at 1 ata) for 90 min, and analyzed for aggregation, protein release, ()NO production, and activation. RESULTS: HBO induced 29.8+/-3.0% of platelets to aggregate compared with CON (5.5+/-0.9%). Proteins observed to be released in greater abundance from HBO- compared with CON-treated platelets included 14-3-3 zeta and alpha-2-macroglobulin. Release of ()NO by platelets was unaffected following exposure to HBO, as was platelet activation as measured by surface expression of PECAM-1, CD62P and the activated form of alpha(IIB)beta(IIIa). CONCLUSIONS: Exposure to HBO induces both platelet aggregation and protein release. Further study will better define the precise mechanisms and effects of HBO on platelet activation.

Determination of S-nitrosothiols in biological and clinical samples using electron paramagnetic resonance spectrometry with spin trapping.

S-Nitroso moieties, such as the S-nitroso group within S-nitrosated albumin, constitute a potential endogenous reservoir of nitric oxide (NO.) in human tissues and other biological systems. Moreover, S-nitroso compounds are under investigation as therapeutic agents in humans. Therefore, it is important to be able to detect S-nitrosothiols (RSNOs) in human extracellular fluids, such as plasma and synovial fluid, as well as other biological samples. This chapter describes a method for the determination of S-nitrosothiols in biofluids. The method is based on electron paramagnetic resonance (EPR) spectrometry, in combination with spin trapping using a ferrous ion complex of the iron chelator N-methyl-d-glucamine dithiocarbamate under alkaline conditions. This iron complex mediates the decomposition of RSNO to NO., as well as spin trapping the generated NO.. The resulting spin adduct has a unique EPR signal that can be quantified.

A single exposure to hyperbaric oxygen does not cause oxidative stress in isolated platelets: no effect on superoxide dismutase, catalase, or cellular ATP.

OBJECTIVES: The aim of the study was to investigate whether a single hyperbaric oxygen exposure causes oxidative stress in isolated platelets. DESIGN AND METHODS: Isolated horse platelets were exposed to 100% oxygen at 2.2 atmospheres, or 100% oxygen under normobaric conditions, or air under normobaric conditions for 90 min. RESULTS: There were no differences in platelet SOD activity between conditions, but there was a rise in SOD in all cases after 24 h (in control platelets at 24 h, SOD was 11.9 +/- 1.9 nmol/min/mg protein compared to initial background levels of 8.2 +/- 1.9 nmol/min/mg protein) (P < 0.05). Neither platelet catalase activity nor platelet GSH concentration changed over time, nor between conditions (catalase activity remained at around 12 units/mg protein, and GSH at around 1.58 nmol/mg protein). CONCLUSIONS: These data suggest that a single HBO exposure has no detrimental effect on platelet biochemistry, and does not cause overt oxidative stress in vitro.