Burnout among community service doctors in South Africa.

BACKGROUND:  Burnout in doctors is an important issue with far-reaching consequences. Community service doctors may be particularly vulnerable because of their specific roles (rural settings, junior positions and reduced supervision). AIM:  This study aimed to determine the prevalence of burnout among community service doctors in South Africa (SA), the potential contributory and protective factors and the consequences thereof. SETTING:  This was a national study of community service doctors in SA. METHODS:  A quantitative, descriptive cross-sectional study was performed. The Maslach Burnout Inventory was used to measure burnout. The online questionnaire also included demographic data, workplace and individual characteristics. RESULTS:  Of the 208 community service doctors analysed, 89% and 94% had high emotional exhaustion and depersonalisation, respectively, while 97% had a low personal accomplishment. Mental illness, financial difficulties, unmanageable volume of patients and female gender were found to be potential contributory factors. Having manageable patient volumes, satisfaction with their decision to study medicine, talking to colleagues and feeling supported by healthcare facility management were among the significant potential protective factors. Significant potential consequences of burnout included: leaving the government sector, ever being diagnosed with a mental illness, using alcohol as a coping mechanism and possible current major depression. CONCLUSION:  Burnout among community service doctors in SA is highly prevalent with significant potential consequences. There are a number of modifiable possible contributory and protective factors identified that may be targets for mental health interventions.Contribution: Healthcare burnout research is lacking in the African and specifically SA context. This void includes community service doctors.

The voice and swallowing profile of adults with laryngotracheal stenosis before and after reconstructive surgery: A prospective, descriptive observational study.

OBJECTIVES: Airway reconstruction for laryngo tracheal stenosis (LTS) improves dyspnoea. There is little evidence relating to impact upon voice and swallowing. We explored voice and swallowing outcomes in adults with LTS before and after reconstructive surgery. DESIGN: Outcome measures were collected pre-reconstructive surgery, two-weeks post-surgery and up to 4-6 months post-surgery. SETTING: Tertiary referral centre. PARTICIPANTS: With ethical approval, twenty consecutive adult (≥18 years) LTS patients undergoing airway reconstruction were prospectively recruited. MAIN OUTCOME MEASURES: These included physiological values (maximum phonation time (MPT) and fundamental frequency; penetration aspiration score, residue score), clinician-reported (GRBAS, functional oral intake score, 100ml Water Swallow Test) and patient-reported outcomes (Voice Handicap Index-10, Reflux Symptoms Index, Eating Assessment Tool, Dysphagia Handicap Index). RESULTS: The observational study identified patient-reported and clinician-reported voice and swallow difficulties pre- and post-surgery; median and interquartile range are reported at each time point: Voice Handicap Index-10 23 (8-31); 20.5 (9-33.5), 24.5 (12.5-29); Dysphagia Handicap Index 9 (0-37); 13 (7-44); 15 (4-34); GRBAS grade 1(1-2); 2 (1-2.5); 2(1-2); 100ml Water Swallow Test volume score 16.7 (11.1-20); 14.3 (12.5-16.7); 16.7 (14.3-20.0); 100ml Water Swallow Test capacity score 16.3 ± 9.0; 11.0 ± 4.1; 12.5 ± 2.6. CONCLUSIONS: We present the first prospective data on voice and swallowing outcomes in adults with LTS before and after reconstructive surgery. The variability of the outcomes was higher than expected but importantly, for many the voice and swallow outcomes were not within normal limits before surgery. The clinical value of the study demonstrates the need for individual assessment and management of LTS patients' voice and swallowing.

Mindfulness as a Potential Moderator Between Child Behavior Problems and Maternal Well-Being.

Mindfulness-based programs can help lower psychological distress among parents of children with developmental disabilities. However, less is known about the functions of mindfulness in relation to parental outcomes. In a cross-sectional survey, mothers of children with developmental disabilities (N = 313) reported on their child's behavior problems, trait mindfulness, mindful parenting, and a range of outcomes (anxiety and depression symptoms, parenting stress, family satisfaction, and positive gain). Neither trait mindfulness or mindful parenting acted as moderators between child behavior problems and outcome variables, although both had main effect (compensatory) associations with parent outcomes. Benefits of mindfulness-based programs may be general rather than specifically in the context of high child behavior problems, given the lack of evidence for the moderating function of mindfulness.

Reductive Photocycloreversion of Cyclobutane Dimers Triggered by Guanines.

The quest for simple systems achieving the photoreductive splitting of four-membered ring compounds is a matter of interest not only in organic chemistry but also in biochemistry to mimic the activity of DNA photorepair enzymes. In this context, 8-oxoguanine, the main oxidatively generated lesion of guanine, has been shown to act as an intrinsic photoreductant by transferring an electron to bipyrimidine lesions and provoking their cycloreversion. But, in spite of appropriate photoredox properties, the capacity of guanine to repair cyclobutane pyrimidine dimer is not clearly established. Here, dyads containing the cyclobutane thymine dimer and guanine or 8-oxoguanine are synthesized, and their photoreactivities are compared. In both cases, the splitting of the ring takes place, leading to the formation of thymine, with a quantum yield 3.5 times lower than that for the guanine derivative. This result is in agreement with the more favored thermodynamics determined for the oxidized lesion. In addition, quantum chemistry calculations and molecular dynamics simulations are carried out to rationalize the crucial aspects of the overall cyclobutane thymine dimer photoreductive repair triggered by the nucleobase and its main lesion.

"Sometimers, Alzheimer's? I love that! That's definitely me": Readers' Responses to Fictional Dementia Narratives.

This article presents findings from an interdisciplinary project which invited readers to experience the impact of dementia via fictional characters' narratives. Combining methods from critical gerontology and literary linguistics-a field that examines the language of literature-we undertook an empirical reader response study of dementia fiction. We constructed a large corpus of dementia fiction; selecting 12 extracts, each containing first-hand, focalized accounts of fictional characters' experiences of living with dementia. Readers (31) were purposively sampled for 4 separate reading groups-student social workers (9); general public (9); family carers (6); and people with dementia (7). Over 6 weeks they engaged in separate, facilitated, on-line group discussions of extracts. Discussions were independently coded using ATLAS.ti. Although readers from all 4 groups reported that fictional characters drew them into the internal life of someone with dementia, some carers questioned whether fictional characters' experiences were plausible. Readers with dementia recognized themselves in the extracts; viewing fictional characters as eloquent envoys of their lived experiences of diagnosis, social isolation, loss of language, and use of humor. Fictional characters offer an entry point for understanding contrasts in caregiver and care-receiver experiences of dementia. Fictional characters are potentially useful for moving dementia narratives beyond monstrous cultural metaphors and onto a disability-based rights agenda.

Discovery of CVN636: A Highly Potent, Selective, and CNS Penetrant mGluR7 Allosteric Agonist.

The low affinity metabotropic glutamate receptor mGluR7 has been implicated in numerous CNS disorders; however, a paucity of potent and selective activators has hampered full delineation of the functional role and therapeutic potential of this receptor. In this work, we present the identification, optimization, and characterization of highly potent, novel mGluR7 agonists. Of particular interest is the chromane CVN636, a potent (EC50 7 nM) allosteric agonist which demonstrates exquisite selectivity for mGluR7 compared to not only other mGluRs, but also a broad range of targets. CVN636 demonstrated CNS penetrance and efficacy in an in vivo rodent model of alcohol use disorder. CVN636 thus has potential to progress as a drug candidate in CNS disorders involving mGluR7 and glutamatergic dysfunction.

How a highly acidic SH3 domain folds in the absence of its charged peptide target.

Charged residues on the surface of proteins are critical for both protein stability and interactions. However, many proteins contain binding regions with a high net-charge that may destabilize the protein but are useful for binding to oppositely charged targets. We hypothesized that these domains would be marginally stable, as electrostatic repulsion would compete with favorable hydrophobic collapse during folding. Furthermore, by increasing the salt concentration we predict that these protein folds would be stabilized by mimicking some of the favorable electrostatic interactions that take place during target binding. We varied the salt and urea concentrations to probe the contributions of electrostatic and hydrophobic interactions for the folding of the 60-residue yeast SH3 domain found in Abp1p. The SH3 domain was significantly stabilized with increased salt concentrations according to the Debye-Huckel limiting law. Molecular dynamics and NMR show that sodium ions interact with all 15 acidic residues but do little to change backbone dynamics or overall structure. Folding kinetics experiments show that the addition of urea or salt primarily affects the folding rate, indicating that almost all the hydrophobic collapse and electrostatic repulsion occurs in the transition state. After the transition state formation, modest yet favorable short-range salt-bridges are formed along with hydrogen bonds, as the native state fully folds. Thus, hydrophobic collapse offsets electrostatic repulsion to ensure this highly charged binding domain can still fold and be ready to bind to its charged peptide targets, a property that is likely evolutionarily conserved over one billion years. Statement for broader audience: Some protein domains are highly charged because they are adapted to bind oppositely charged proteins and nucleic acids. However, it is unknown how these highly charged domains fold as during folding there will be significant repulsion between like-charges. We investigate how one of these highly charged domains folds in the presence of salt, which can screen the charge repulsion and make folding easier, allowing us to understand how folding occurs despite the protein’s high charge. Supplementary material: Supplementary material document containing additional details on protein expression methods, thermodynamics and kinetics equations, and the effect of urea on electrostatic interactions, as well as 4 supplemental figures and 4 supplemental data tables. ( Supplementary_Material.docx ), 15 pages Supplemental excel file containing covariation data across AbpSH3 orthologs ( FileS1.xlsx ).

Mindfulness-based programmes and 'bigger than self' issues: protocol for a scoping review.

INTRODUCTION: Mindfulness-based programmes (MBPs) have an established, growing evidence base as interventions to optimise health, well-being and performance of individual participants. Emerging evidence suggests that MBPs also enhance prosociality, encouraging individuals to contribute to positive social change. This study focuses on the potential of MBPs to facilitate development of participants' inner resources that support prosocial shifts. The review seeks to detect shifts in MBP benefit from individual toward 'bigger than self', informing and empowering individual and collective responses to complex societal and global issues. The review aims to map current literature on MBPs and social change, into a descriptive overview with commentary on quality, trends, theoretical models and gaps, and on how training in MBPs potentially enables individual and collective responses to societal and global issues. Recommendations for future directions for researchers seeking to advance this evidence base, and practitioners developing innovative MBPs for this purpose will be provided. METHODS AND ANALYSIS: A scoping review of peer-reviewed literature will be undertaken and reported on according to the Joanna Briggs Institute (JBI) Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidance. Systematic searches of four scientific databases will be undertaken to identify potentially eligible articles published from all time to current date. Data will be extracted using an extraction template and analysed descriptively using narrative synthesis. ETHICS AND DISSEMINATION: This scoping review involves no human participants, so ethics is not required. Findings will be shared through professional networks, conference presentations and journal publication.

How a highly acidic SH3 domain folds in the absence of its charged peptide target.

Charged residues on the surface of proteins are critical for both protein stability and interactions. However, many proteins contain binding regions with a high net charge that may destabilize the protein but are useful for binding to oppositely charged targets. We hypothesized that these domains would be marginally stable, as electrostatic repulsion would compete with favorable hydrophobic collapse during folding. Furthermore, by increasing the salt concentration, we predict that these protein folds would be stabilized by mimicking some of the favorable electrostatic interactions that take place during target binding. We varied the salt and urea concentrations to probe the contributions of electrostatic and hydrophobic interactions for the folding of the yeast SH3 domain found in Abp1p. The SH3 domain was significantly stabilized with increased salt concentrations due to Debye-Huckel screening and a nonspecific territorial ion-binding effect. Molecular dynamics and NMR show that sodium ions interact with all 15 acidic residues but do little to change backbone dynamics or overall structure. Folding kinetics experiments show that the addition of urea or salt primarily affects the folding rate, indicating that almost all the hydrophobic collapse and electrostatic repulsion occur in the transition state. After the transition state formation, modest yet favorable short-range salt bridges are formed along with hydrogen bonds, as the native state fully folds. Thus, hydrophobic collapse offsets electrostatic repulsion to ensure this highly charged binding domain can still fold and be ready to bind to its charged peptide targets, a property that is likely evolutionarily conserved over 1 billion years.

An application of the stress-diathesis model: A review about the association between smoking tobacco, smoking cessation, and mental health

Background: Worldwide, approximately 24% of all adults smoke, but smoking is up to twice as prevalent in people with mental ill-health. There is growing evidence that smoking may be a causal risk factor in the development of mental illness, and that smoking cessation leads to improved mental health. Methods: In this scholarly review we have: (1) used a modern adaptation of the Bradford-Hill criteria to bolster the argument that smoking could cause mental ill-health and that smoking cessation could reverse these effects, and (2) by considering psychological, biological, and environmental factors, we have structured the evidence to-date into a stress-diathesis model. Results: Our model suggests that smoking is a psychobiological stressor, but that the magnitude of this effect is mediated and modulated by the individual's diathesis to develop mental ill-health and other vulnerability and protective factors. We explore biological mechanisms that underpin the model, such as tobacco induced damage to neurological systems and oxidative stress pathways. Furthermore, we discuss evidence indicating that it is likely that these systems repair after smoking cessation, leading to better mental health. Conclusion: Based on a large body of literature including experimental, observational, and novel causal inference studies, there is consistent evidence showing that smoking can negatively affect the brain and mental health, and that smoking cessation could reverse the mental ill-health caused by smoking. Our model suggests that smoking prevention and treatment strategies have a role in preventing and treating mental illness as well as physical illness. (AU)

The Fit-for-Purpose Model: Conceptualizing and Managing Chronic Nonspecific Low Back Pain as an Information Problem.

Chronic nonspecific low back pain (LBP) is a complex and multifaceted problem. The following Perspective piece tries to help make sense of this complexity by describing a model for the development and maintenance of persistent LBP that integrates modifiable factors across the biopsychosocial spectrum. The Fit-for-Purpose model posits the view that chronic nonspecific LBP represents a state in which the person in pain holds strong and relatively intransient internal models of an immutably damaged, fragile, and unhealthy back, and information that supports these models is more available and trustworthy than information that counters them. This Perspective proposes a corresponding treatment framework for persistent pain that aims to shift internal models of a fragile, damaged, unhealthy, and unchangeable self toward the formulation of the back as healthy, strong, adaptable, and fit for purpose and to provide the system with precise and trustworthy evidence that supports this supposition while minimizing information that works against it.

An application of the stress-diathesis model: A review about the association between smoking tobacco, smoking cessation, and mental health.

Background: Worldwide, approximately 24% of all adults smoke, but smoking is up to twice as prevalent in people with mental ill-health. There is growing evidence that smoking may be a causal risk factor in the development of mental illness, and that smoking cessation leads to improved mental health. Methods: In this scholarly review we have: (1) used a modern adaptation of the Bradford-Hill criteria to bolster the argument that smoking could cause mental ill-health and that smoking cessation could reverse these effects, and (2) by considering psychological, biological, and environmental factors, we have structured the evidence to-date into a stress-diathesis model. Results: Our model suggests that smoking is a psychobiological stressor, but that the magnitude of this effect is mediated and modulated by the individual's diathesis to develop mental ill-health and other vulnerability and protective factors. We explore biological mechanisms that underpin the model, such as tobacco induced damage to neurological systems and oxidative stress pathways. Furthermore, we discuss evidence indicating that it is likely that these systems repair after smoking cessation, leading to better mental health. Conclusion: Based on a large body of literature including experimental, observational, and novel causal inference studies, there is consistent evidence showing that smoking can negatively affect the brain and mental health, and that smoking cessation could reverse the mental ill-health caused by smoking. Our model suggests that smoking prevention and treatment strategies have a role in preventing and treating mental illness as well as physical illness.

Acceptability of integrating smoking cessation treatment into routine care for people with mental illness: A qualitative study.

INTRODUCTION: Improving Access to Psychological Therapies (IAPTs) Services could offer smoking cessation treatment to improve physical and psychological outcomes for service users, but it currently does not. This study aimed to understand participants' views and experiences of receiving a novel smoking cessation intervention as part of the ESCAPE trial (intEgrating Smoking Cessation treatment As part of usual Psychological care for dEpression and anxiety). We used the Capability, Opportunity and Motivation Model of Behaviour (COM-B) to understand the (i) acceptability of the integrated smoking cessation treatment, (ii) views of psychological well-being practitioners' (PWPs) ability to deliver the smoking cessation treatment and (iii) positive and negative impacts of smoking cessation treatment. METHODS: This was a qualitative study embedded within a feasibility randomized-controlled trial (ESCAPE) in primary care services in the United Kingdom (IAPT). Thirty-six participants (53% female) from both usual care and intervention arms of the ESCAPE trial, including both quitters and nonquitters, were interviewed using semi-structured interviews. Data were analysed using a framework approach to thematic analysis, using the COM-B as a theoretical frame. RESULTS: Psychological Capability: Integrated smoking cessation treatment was acceptable and encouraged participants to reflect on their mental health. Some participants found it difficult to understand nicotine withdrawal symptoms. MOTIVATION: Participants were open to change during the event of presenting to IAPT. Some described being motivated to take part in the intervention by curiosity, to see whether quitting smoking would help their mental health. Physical Opportunity: IAPT has a natural infrastructure for supporting integrated treatment, but there were some barriers such as session duration and interventions feeling segmented. Social Opportunity: Participants viewed PWPs as having good interpersonal skills to deliver a smoking cessation intervention. CONCLUSION: People with common mental illness generally accepted integrated smoking cessation and mental health treatment. Smoking cessation treatment fits well within IAPT's structure; however, there are barriers to implementation. PATIENT OR PUBLIC CONTRIBUTION: Before data collection, we consulted with people with lived experience of smoking and/or mental illness and lay public members regarding the aims, design and interview schedules. After analysis, two people with lived experience of smoking and mental illness individually gave feedback on the final themes and quotes.