REDUCING MENTAL HEALTH STIGMA IN MEDICAL STUDENTS AND DOCTORS TOWARDS THEIR PEERS WITH MENTAL HEALTH DIFFICULTIES: A PROTOCOL

Mental health problems are over-represented in doctors and medical students. However, stigma and ‘a culture of shame’ are formidable barriers to mental health services and consequently many doctors and medical students with mental health difficulties continue to suffer in silence despite the availability of effective treatment. Indeed, a recent study on over 2100 female physicians who met the diagnostic criteria for a mental disorder revealed that 50% were reluctant to seek professional help due to fear of exposure to stigma. Left untreated or undertreated, mental health problems in doctors can result in impairment of occupational functioning, compromise patient safety and place considerable strain on the economy (by increasing the amount of sick leave taken). Moreover, the consequences of mental health stigma in the medical profession can be fatal. Dr Daksha Emson, a psychiatrist with bipolar affective disorder, tragically killed herself and her baby daughter during a psychotic episode. An independent inquiry into Dr Emson’s death concluded that she was the victim of stigma in the National Health Service. The mental health of medical students and doctors, in all of its aspects, must therefore be addressed with the urgency that it demands. Stephanie Knaak and colleagues conducted a data synthesis of evaluative studies on anti-stigma programmes for healthcare providers and identified six key ingredients one of which was a personal testimony from a trained speaker who has lived experience of mental illness. In this paper we outline a study protocol with the aim of answering the following research question, ‘Does attending an anti-stigma programme comprised of a medic with first-hand experience of a mental health condition cause immediate and sustained reductions in mental health stigma from medical students and doctors towards their peers with mental health difficulties?

REDUCING MENTAL HEALTH STIGMA IN MEDICAL STUDENTS AND DOCTORS TOWARDS THEIR PEERS WITH MENTAL HEALTH DIFFICULTIES: A PROTOCOL

Mental health problems are over-represented in doctors and medical students. However, stigma and ‘a culture of shame’ are formidable barriers to mental health services and consequently many doctors and medical students with mental health difficulties continue to suffer in silence despite the availability of effective treatment. Indeed, a recent study on over 2100 female physicians who met the diagnostic criteria for a mental disorder revealed that 50% were reluctant to seek professional help due to fear of exposure to stigma. Left untreated or undertreated, mental health problems in doctors can result in impairment of occupational functioning, compromise patient safety and place considerable strain on the economy (by increasing the amount of sick leave taken). Moreover, the consequences of mental health stigma in the medical profession can be fatal. Dr Daksha Emson, a psychiatrist with bipolar affective disorder, tragically killed herself and her baby daughter during a psychotic episode. An independent inquiry into Dr Emson’s death concluded that she was the victim of stigma in the National Health Service. The mental health of medical students and doctors, in all of its aspects, must therefore be addressed with the urgency that it demands. Stephanie Knaak and colleagues conducted a data synthesis of evaluative studies on anti-stigma programmes for healthcare providers and identified six key ingredients one of which was a personal testimony from a trained speaker who has lived experience of mental illness. In this paper we outline a study protocol with the aim of answering the following research question, ‘Does attending an anti-stigma programme comprised of a medic with first-hand experience of a mental health condition cause immediate and sustained reductions in mental health stigma from medical students and doctors towards their peers with mental health difficulties?

Probing the dynamic nature of self-assembling cyclic peptide-polymer nanotubes in solution and in mammalian cells

Self-assembling cyclic peptide–polymer nanotubes have emerged as a fascinating supramolecular system, well suited for a diverse range of biomedical applications. Due to their well-defined diameter, tunable peptide anatomy, and ability to disassemble in situ, they have been investigated as promising materials for numerous applications including biosensors, antimicrobials, and drug delivery. Despite this continuous effort, the underlying mechanisms of assembly and disassembly are still not fully understood. In particular, the exchange of units between individual assembled nanotubes has been overlooked so far, despite its knowledge being essential for understanding their behavior in different environments. To investigate the dynamic nature of these systems, cyclic peptide–polymer nanotubes are synthesized, conjugated with complementary dyes, which undergo a Förster resonance energy transfer (FRET) in close proximity. Model conjugates enable to demonstrate not only that their self-assembly is highly dynamic and not kinetically trapped, but also that the self-assembly of the conjugates is strongly influenced by both solvent and concentration. Additionally, the versatility of the FRET system allows studying the dynamic exchange of these systems in mammalian cells in vitro using confocal microscopy, demonstrating the exchange of subunits between assembled nanotubes in the highly complex environment of a cell

Care-seeking correlates of acute respiratory illness among sheltered adults experiencing homelessness in Seattle, WA, 2019: a community-based cross-sectional study

ObjectiveMultifarious barriers to accessing healthcare services among people experiencing homelessness (PEH) lead to delays in seeking care for acute infections, including those caused by respiratory viruses. PEH are at high risk of acute respiratory illness (ARI)-related complications, especially in shelter settings that may facilitate virus spread, yet data characterizing healthcare utilization for ARI episodes among sheltered PEH remained limited.MethodsWe conducted a cross-sectional study of viral respiratory infection among adult residents at two homeless shelters in Seattle, Washington between January and May 2019. We assessed factors associated with seeking medical care for ARI via self-report. We collected illness questionnaires and nasal swabs were tested for respiratory viruses by reverse transcription quantitative real-time PCR (RT-qPCR).ResultsWe observed 825 encounters from 649 unique participants; 241 (29.2%) encounters reported seeking healthcare for their ARI episode. Seasonal influenza vaccine receipt (adjusted prevalence ratio [aPR] 1.39, 95% CI 1.02–1.88), having health insurance (aPR 2.77, 95% CI 1.27–6.02), chronic lung conditions (aPR 1.55, 95% CI 1.12-2.15), and experiencing influenza-like-illness symptoms (aPR 1.63, 95% CI 1.20 - 2.20) were associated with increased likelihood of seeking care. Smoking (aPR 0.65, 95% CI 0.45-0.92) was associated with decreased likelihood of seeking care.DiscussionFindings suggest that care seeking for viral respiratory illness among PEH may be supported by prior engagement with primary healthcare services. Strategies to increase healthcare utilization may lead to earlier detection of respiratory viruses

Isotopic composition of sinking particles: Oil effects, recovery and baselines in the Gulf of Mexico, 2010–2015

The extensive release of oil during the 2010 Deepwater Horizon spill in the northern Gulf of Mexico perturbed the pelagic ecosystem and associated sinking material. To gauge the recovery and post-spill baseline sources, we measured Δ14C, δ13C and δ34S of sinking particles near the spill site and at a reference site and natural seep site. Particulates were collected August 2010–April 2016 in sediment traps moored at sites with depths of 1160–1660 m. Near the spill site, changes in Δ14C indicated a 3-year recovery period, while δ34S indicated 1–2 years, which agreed with estimates of 1–2 years based on hydrocarbon composition. Under post-spill baseline conditions, carbon inputs to sinking particulates in the northern Gulf were dominated by surface marine production (80–85%) and riverine inputs (15–20%). Near the spill site, Δ14C values were depleted in October 2010 (–140 to –80‰), increasing systematically by 0.07 ± 0.02‰ day–1 until July 2013 when values reached –3.2 ± 31.0‰. This Δ14C baseline was similar to particulates at the reference site (3.8 ± 31.1‰). At both sites, δ13C values stayed constant throughout the study period (–21.9 ± 0.5‰ and –21.9 ± 0.9‰, respectively). δ34S near the spill site was depleted (7.4 ± 3.1‰) during October 2010–September 2011, but enriched (16.9 ± 2.0‰) and similar to the reference site (16.2 ± 3.1‰) during November 2012–April 2015. At the seep site, Δ14C values were –21.7 ± 45.7‰ except during August 2012–January 2013 when a significant Δ14C depletion of –109.0 ± 29.1‰ was observed. We interpret this depletion period, also observed in δ13C data, as caused by the incorporation of naturally seeped oil into sinking particles. Determination of post-spill baselines for these isotopic signatures allows for evaluation of anthropogenic inputs in future

Remembering the work of Phillip L. Geissler: A coda to his scientific trajectory

Phillip L. Geissler made important contributions to the statistical mechanics of biological polymers, heterogeneous materials, and chemical dynamics in aqueous environments. He devised analytical and computational methods that revealed the underlying organization of complex systems at the frontiers of biology, chemistry, and materials science. In this retrospective, we celebrate his work at these frontiers

Suv4-20h Histone Methyltransferases Promote Neuroectodermal Differentiation by Silencing the Pluripotency-Associated Oct-25 Gene

Post-translational modifications (PTMs) of histones exert fundamental roles in regulating gene expression. During development, groups of PTMs are constrained by unknown mechanisms into combinatorial patterns, which facilitate transitions from uncommitted embryonic cells into differentiated somatic cell lineages. Repressive histone modifications such as H3K9me3 or H3K27me3 have been investigated in detail, but the role of H4K20me3 in development is currently unknown. Here we show that Xenopus laevis Suv4-20h1 and h2 histone methyltransferases (HMTases) are essential for induction and differentiation of the neuroectoderm. Morpholino-mediated knockdown of the two HMTases leads to a selective and specific downregulation of genes controlling neural induction, thereby effectively blocking differentiation of the neuroectoderm. Global transcriptome analysis supports the notion that these effects arise from the transcriptional deregulation of specific genes rather than widespread, pleiotropic effects. Interestingly, morphant embryos fail to repress the Oct4-related Xenopus gene Oct-25. We validate Oct-25 as a direct target of xSu4-20h enzyme mediated gene repression, showing by chromatin immunoprecipitaton that it is decorated with the H4K20me3 mark downstream of the promoter in normal, but not in double-morphant, embryos. Since knockdown of Oct-25 protein significantly rescues the neural differentiation defect in xSuv4-20h double-morphant embryos, we conclude that the epistatic relationship between Suv4-20h enzymes and Oct-25 controls the transit from pluripotent to differentiation-competent neural cells. Consistent with these results in Xenopus, murine Suv4-20h1/h2 double-knockout embryonic stem (DKO ES) cells exhibit increased Oct4 protein levels before and during EB formation, and reveal a compromised and biased capacity for in vitro differentiation, when compared to normal ES cells. Together, these results suggest a regulatory mechanism, conserved between amphibians and mammals, in which H4K20me3-dependent restriction of specific POU-V genes directs cell fate decisions, when embryonic cells exit the pluripotent state

Mucolytic treatment of chronic rhinosinusitis in a murine model of primary ciliary dyskinesia

Background: Genetic defects in motile cilia cause primary ciliary dyskinesia (PCD), a rare disease with no specific therapeutics. Individuals with PCD often have impaired fertility and laterality defects and universally suffer from upper and lower airway diseases. Chronic rhinosinusitis is a universal feature of PCD, and mucus accumulation and subsequent infections of the sinonasal cavity cause significant morbidity in individuals with PCD. Despite this, there are no approved treatments that specifically target mucus.Objective: The goals of this study were to determine whether computed tomography (CT) imaging could be used to quantify mucus accumulation and whether the use of a mucolytic agent to reduce disulfide cross-links present in mucins would improve the effectiveness of nasal lavage at removing mucus in a murine model of PCD.Methods: Adult mice with a deletion of the axonemal dynein Dnaic1 were imaged using CT scanning to characterize mucus accumulation. The animals were then treated by nasal lavage with saline, with/without the disulfide-reducing agent tris(2-carboxyethyl)phosphine. Post-treatment CT scans were used to quantify improvement in the sinonasal cavity.Results: Mucus accumulation in the nasal cavity was readily quantified by CT. Compared to sham-treated control animals, nasal lavage with/without a mucolytic agent resulted in a significant reduction of accumulated mucus (p < 0.01). Treatment with the mucolytic agent showed a greater reduction of accumulated mucus than treatment with saline alone.Conclusion: The results suggest that inclusion of a mucolytic agent may increase the effectiveness of nasal lavage at reducing mucus burden in PCD