The genomic landscapes of individual melanocytes from human skin.

Every cell in the human body has a unique set of somatic mutations, but it remains difficult to comprehensively genotype an individual cell1. Here we describe ways to overcome this obstacle in the context of normal human skin, thus offering a glimpse into the genomic landscapes of individual melanocytes from human skin. As expected, sun-shielded melanocytes had fewer mutations than sun-exposed melanocytes. However, melanocytes from chronically sun-exposed skin (for example, the face) had a lower mutation burden than melanocytes from intermittently sun-exposed skin (for example, the back). Melanocytes located adjacent to a skin cancer had higher mutation burdens than melanocytes from donors without skin cancer, implying that the mutation burden of normal skin can be used to measure cumulative sun damage and risk of skin cancer. Moreover, melanocytes from healthy skin commonly contained pathogenic mutations, although these mutations tended to be weakly oncogenic, probably explaining why they did not give rise to discernible lesions. Phylogenetic analyses identified groups of related melanocytes, suggesting that melanocytes spread throughout skin as fields of clonally related cells that are invisible to the naked eye. Overall, our results uncover the genomic landscapes of individual melanocytes, providing key insights into the causes and origins of melanoma.

'It was the deepest level of companionship': peer-to-peer experience of supporting community-dwelling older people with depression - a qualitative study.

BACKGROUND: There is an ample body of literature examining the experiences and outcomes of peer support services for mental health recovery in western countries. However, formal peer support is only recently adapted and piloted to alleviate depression among older people, and little is known about how the peer-to-peer model might be lived out in the older Chinese population. This qualitative study investigated peer supporters' (PS) perspectives of their roles and experiences of rendering formal peer support to community-dwelling older adults at risk of or living with depression in Hong Kong. METHODS: The study adopted a qualitative design. Five semi-structured focus groups were conducted with 27 trained peer supporters between ages 54-74 (21 females and 6 males) who had provided peer-to-peer support to older adults at risk of or living with depression in the community for at least 12 months. Thematic analysis was employed to derive content and meanings from the focus group transcripts. RESULTS: Participants' mean age was 61.9 years; two-thirds of them were retired and the rest still engaged in part-time or full-time employment. Four themes were identified in relations to the roles and experiences in rendering the peer support services: (1) peerness in health and age-related lived experiences; (2) companionship, social and emotional ties beyond formal support; (3) meaningful roles to facilitate older people's functional ability; and (4) hopes and actions against the undesirable outcomes of aging. Being a PS might provide meaningful roles for persons in transition to or living in late adulthood, and enable community-dwelling older adults with depression to maintain functional ability. On the other hand, defining the concept of 'peer' beyond the shared experience of mental distress, ensuring a healthy boundary between the peers and the service users, maintaining a careful balance between time-limited formal support and stable social ties, and providing self-management training and on-going support appear crucial. CONCLUSIONS: This study of PS' perspectives and experiences offer insights into the age-specific dimension of the peer relationship. Despite the promising effects it might offer, careful implementation of peer support among older adults is warranted to safeguard against the ensuing loss of meaningful social ties and the potential emotional distress.

Impact of Citrus Essential Oil Diffusion on Health Care Staff's Stress Levels: An Evidence-Based Practice Project.

Essential oil diffusion can decrease stress. In one hospital, citrus essential oils were diffused over 6 weeks. Staff completed surveys of their stress levels before and after diffusion. Staff did not report a significant reduction in stress; however, there was an increase in feeling "relaxed."

Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial.

IMPORTANCE: Retinal ganglion cells endure significant metabolic stress in glaucoma but maintain capacity to recover function. Nicotinamide, a precursor of NAD+ , is low in serum of glaucoma patients and its supplementation provides robust protection of retinal ganglion cells in preclinical models. However, the potential of nicotinamide in human glaucoma is unknown. BACKGROUND: To examine the effects of nicotinamide on inner retinal function in glaucoma, in participants receiving concurrent glaucoma therapy. DESIGN: Crossover, double-masked, randomized clinical trial. Participants recruited from two tertiary care centres. PARTICIPANTS: Fifty-seven participants, diagnosed and treated for glaucoma. METHODS: Participants received oral placebo or nicotinamide and reviewed six-weekly. Participants commenced 6 weeks of 1.5 g/day then 6 weeks of 3.0 g/day followed by crossover without washout. Visual function measured using electroretinography and perimetry. MAIN OUTCOME MEASURES: Change in inner retinal function, determined by photopic negative response (PhNR) parameters: saturated PhNR amplitude (Vmax), ratio of PhNR/b-wave amplitude (Vmax ratio). RESULTS: PhNR Vmax improved beyond 95% coefficient of repeatability in 23% of participants following nicotinamide vs 9% on placebo. Overall, Vmax improved by 14.8% [95% CI: 2.8%, 26.9%], (P = .02) on nicotinamide and 5.2% [-4.2%, 14.6%], (P = .27) on placebo. Vmax ratio improved by 12.6% [5.0%, 20.2%], (P = .002) following nicotinamide, 3.6% [-3.4%, 10.5%], (P = .30) on placebo. A trend for improved visual field mean deviation was observed with 27% improving ≥1 dB on nicotinamide and fewer deteriorating (4%) compared to placebo (P = .02). CONCLUSIONS: Nicotinamide supplementation can improve inner retinal function in glaucoma. Further studies underway to elucidate the effects of long-term nicotinamide supplementation.

Mental health service user participation in Chinese culture: a model of independence or interdependence?

BACKGROUND: Current models of user participation in mental health services were developed within Western culture and thus may not be applicable to Chinese communities. AIMS: To present a new model of user participation, which emerged from research within a Chinese community, for understanding the processes of and factors influencing user participation in a non-Western culture. METHOD: Multiple qualitative methods, including focus groups, individual in-depth interviews, and photovoice, were applied within the framework of constructivist grounded theory and collaborative research. RESULTS: Diverging from conceptualizations of user participation with emphasis on civil rights and the individual as a central agent, participants in the study highlighted the interpersonal dynamics between service users and different players affecting the participation intensity and outcomes. They valued a reciprocal relationship with their caregivers in making treatment decisions, cooperated with staff to observe power hierarchies and social harmony, identified the importance of peer support in enabling service engagement and delivery, and emphasized professional facilitation in advancing involvement at the policy level. CONCLUSIONS: User participation in Chinese culture embeds dynamic interdependence. The proposed model adds this new dimension to the existing frameworks and calls for attention to the complex local ecology and cultural consistency in realizing user participation.

Impact of medical academic genealogy on publication patterns: An analysis of the literature for surgical resection in brain tumor patients.

"Academic genealogy" refers to the linking of scientists and scholars based on their dissertation supervisors. We propose that this concept can be applied to medical training and that this "medical academic genealogy" may influence the landscape of the peer-reviewed literature. We performed a comprehensive PubMed search to identify US authors who have contributed peer-reviewed articles on a neurosurgery topic that remains controversial: the value of maximal resection for high-grade gliomas (HGGs). Training information for each key author (defined as the first or last author of an article) was collected (eg, author's medical school, residency, and fellowship training). Authors were recursively linked to faculty mentors to form genealogies. Correlations between genealogy and publication result were examined. Our search identified 108 articles with 160 unique key authors. Authors who were members of 2 genealogies (14% of key authors) contributed to 38% of all articles. If an article contained an authorship contribution from the first genealogy, its results were more likely to support maximal resection (log odds ratio = 2.74, p < 0.028) relative to articles without such contribution. In contrast, if an article contained an authorship contribution from the second genealogy, it was less likely to support maximal resection (log odds ratio = -1.74, p < 0.026). We conclude that the literature on surgical resection for HGGs is influenced by medical academic genealogies, and that articles contributed by authors of select genealogies share common results. These findings have important implications for the interpretation of scientific literature, design of medical training, and health care policy.

Parathyroidectomy for tertiary hyperparathyroidism: A systematic review.

OBJECTIVE: Analyze the efficacy and indications for parathyroidectomy as an intervention for tertiary hyperparathyroidism. DATA SOURCES: PubMed, MEDLINE, and Cochrane Library databases. REVIEW METHODS: A systematic literature search was performed using the. Original research articles in English were retrieved using the search terms ("tertiary hyperparathyroidism" OR "3HPT") AND "parathyroidectomy". Articles were analyzed in regards to their surgical indications, operative endpoints, comparison between different surgical interventions, characterization of disease recurrence rates, and evaluation of alternative medical management. RESULTS: Thirty studies met the criteria for inclusion. Among the studies that report indications for parathyroidectomy, persistent hypercalcemia as well as clinical manifestations of hypercalcemia despite medical therapy predicted which patients would eventually need surgical intervention. The majority of studies comparing the extent of parathyroidectomy recommended a more focused approach to parathyroidectomy when warranted. All studies found that parathyroidectomy was an effective treatment for 3HPT. Three studies discussed alternative conservative approaches. CONCLUSION: Interestingly, hyperparathyroidism alone is not an indication for surgery without other findings; rather, symptomatic hypercalcemia appears to be the main indication. Most studies recommend limited or subtotal parathyroidectomy for 3HPT. The operative endpoint of surgery is not necessarily a return of PTH to normal, but a >50% drop in PTH level even if PTH remains above normal. Additionally, "success" or "cure" is defined as normal calcium levels regardless of whether or not PTH is elevated. It appears the goal of surgery for 3HPT is not a normal PTH value, but a normal calcium level at least six months postoperatively.

'Journal Bias' in peer-reviewed literature: an analysis of the surgical high-grade glioma literature.

The core premise of evidence-based medicine is that clinical decisions are informed by the peer-reviewed literature. To extract meaningful conclusions from this literature, one must first understand the various forms of biases inherent within the process of peer review. We performed an exhaustive search that identified articles exploring the question of whether survival benefit was associated with maximal high-grade glioma (HGG) resection and analysed this literature for patterns of publication. We found that the distribution of these 108 articles among the 26 journals to be non-random (p<0.01), with 75 of the 108 published articles (69%) appearing in 6 of the 26 journals (25%). Moreover, certain journals were likely to publish a large number of articles from the same medical academic genealogy (authors with shared training history and/or mentor). We term the tendency of certain types of articles to be published in select journals 'journal bias' and discuss the implication of this form of bias as it pertains to evidence-based medicine.

Full immersion simulation: validation of a distributed simulation environment for technical and non-technical skills training in Urology.

OBJECTIVE: To evaluate the face, content and construct validity of the distributed simulation (DS) environment for technical and non-technical skills training in endourology. To evaluate the educational impact of DS for urology training. SUBJECTS AND METHODS: DS offers a portable, low-cost simulated operating room environment that can be set up in any open space. A prospective mixed methods design using established validation methodology was conducted in this simulated environment with 10 experienced and 10 trainee urologists. All participants performed a simulated prostate resection in the DS environment. Outcome measures included surveys to evaluate the DS, as well as comparative analyses of experienced and trainee urologist's performance using real-time and 'blinded' video analysis and validated performance metrics. Non-parametric statistical methods were used to compare differences between groups. RESULTS: The DS environment demonstrated face, content and construct validity for both non-technical and technical skills. Kirkpatrick level 1 evidence for the educational impact of the DS environment was shown. Further studies are needed to evaluate the effect of simulated operating room training on real operating room performance. CONCLUSIONS: This study has shown the validity of the DS environment for non-technical, as well as technical skills training. DS-based simulation appears to be a valuable addition to traditional classroom-based simulation training.

Patient involvement in mental health care: culture, communication and caution.

BACKGROUND: Patient or service user involvement in mental health services (MHS) is a hallmark of the recovery approach. OBJECTIVE: In this viewpoint article, we review Tambuyzer et al. paper 'Patient involvement in mental health care: One size does not fit all' in order to express our opinion of their work. We also suggest specific actions that may enhance the implementation of patient involvement in MHS. DISCUSSION: We make three main points about Tambuyzer et al. model. First, the cultural dimension of patient involvement seems underemphasized in the model. Second, the model might be improved if the increasing role of communications technology in patient involvement is taken into consideration. Third, it is important to acknowledge that the process of patient involvement is not linear, and participation is not a homogeneous experience. CONCLUSIONS: We suggest that the model be expanded and that further work be carried out on the implementation of patient involvement in MHS.

Randomised controlled trial of weaning strategies for preterm infants on nasal continuous positive airway pressure.

BACKGROUND: The optimal strategy for weaning very preterm infants from nasal continuous positive airway pressure (NCPAP) is unclear. Reported strategies include weaning NCPAP to a predefined pressure then trialling stopping completely (abrupt wean); alternate periods of increased time off NCPAP whilst reducing time on until the infant is completely weaned (gradual wean); and using high flow nasal cannula (HFNC) to assist the weaning process. The aim of this study was to determine the optimal weaning from NCPAP strategy for very preterm infants. METHODS: A pilot single centre, factorial design, 4-arm randomised controlled trial. Sixty infants born <30 weeks gestation meeting stability criteria on NCPAP were randomly allocated to one of four groups. Group 1: abrupt wean with HFNC; Group 2: abrupt wean without HFNC; Group 3: gradual wean with HFNC; Group 4: gradual wean without HFNC. The primary outcomes were duration of respiratory support, chronic lung disease, length of hospital stay and time to full suck feeds. RESULTS: The primary outcome measures were not significantly different between groups. Group 1 had a significant reduction in duration of NCPAP (group 1: median 1 day; group 2: 24 days; group 3: 15 days; group 4: 24 days; p = 0.002) and earlier corrected gestational age off NCPAP. There was a significant difference in rate of parental withdrawal from the study, with group 2 having the highest rate. Group 3 had a significantly increased duration on HFNC compared to group 1. CONCLUSIONS: Use of high flow nasal cannula may be effective at weaning infants from NCPAP but did not reduce duration of respiratory support or time to full suck feeds. Abrupt wean without the use of HFNC was associated with an increased rate of withdrawal by parent request. TRIAL REGISTRATION: This study is registered at the Australian New Zealand Clinical Trials Registry ( www.anzctr.org.au/). (Registration Number = ACTRN12610001003066).

An exploration of workplace social capital as an antecedent of occupational safety and health climate and outcomes in the Chinese education sector.

PURPOSE: It is widely acknowledged that teachers are at greater risk of work-related health problems. At the same time, employee perceptions of different dimensions of organizational climate can influence their attitudes, performance, and well-being at work. This study applied and extended a safety climate model in the context of the education sector in Hong Kong. Apart from safety considerations alone, the study included occupational health considerations and social capital and tested their relationships with occupational safety and health (OSH) outcomes. METHODS: Seven hundred and four Hong Kong teachers completed a range of questionnaires exploring social capital, OSH climate, OSH knowledge, OSH performance (compliance and participation), general health, and self-rated health complaints and injuries. Structural equation modeling (SEM) was used to analyze the relationships between predictive and outcome variables. RESULTS: SEM analysis revealed a high level of goodness of fit, and the hypothesized model including social capital yielded a better fit than the original model. Social capital, OSH climate, and OSH performance were determinants of both positive and negative outcome variables. In addition, social capital not only significantly predicted general health directly, but also had a predictive effect on the OSH climate-behavior-outcome relationship. CONCLUSIONS: This study makes a contribution to the workplace social capital and OSH climate literature by empirically assessing their relationship in the Chinese education sector.

Calculating Relative Lung Perfusion Using Fluoroscopic Sequences and Image Analysis: The Fluoroscopic Flow Calculator.

BACKGROUND: Maldistribution of pulmonary blood flow in patients with congenital heart disease impacts exertional performance and pulmonary artery growth. Currently, measurement of relative pulmonary perfusion can only be performed outside the catheterization laboratory. We sought to develop a tool for measuring relative lung perfusion using readily available fluoroscopy sequences. METHODS: A retrospective cohort study was conducted on patients with conotruncal anomalies who underwent lung perfusion scans and subsequent cardiac catheterizations between 2011 and 2022. Inclusion criteria were nonselective angiogram of pulmonary vasculature, oblique angulation ≤20°, and an adequate view of both lung fields. A method was developed and implemented in 3D Slicer's SlicerHeart extension to calculate the amount of contrast that entered each lung field from the start of contrast injection and until the onset of levophase. The predicted perfusion distribution was compared with the measured distribution of pulmonary blood flow and evaluated for correlation, accuracy, and bias. RESULTS: In total, 32% (79/249) of screened studies met the inclusion criteria. A strong correlation between the predicted flow split and the measured flow split was found (R2=0.83; P<0.001). The median absolute error was 6%, and 72% of predictions were within 10% of the true value. Bias was not systematically worse at either extreme of the flow distribution. The prediction was found to be more accurate for either smaller and younger patients (age 0-2 years), for right ventricle injections, or when less cranial angulations were used (≤20°). In these cases (n=40), the prediction achieved R2=0.87, median absolute error of 5.5%, and 78% of predictions were within 10% of the true flow. CONCLUSIONS: The current study demonstrates the feasibility of a novel method for measuring relative lung perfusion using conventional angiograms. Real-time measurement of lung perfusion at the catheterization laboratory has the potential to reduce unnecessary testing, associated costs, and radiation exposure. Further optimization and validation is warranted.

Molecular effects of indoor tanning.

Background: Tanning bed users have a significantly increased risk of melanoma, but it remains unclear how indoor tanning drives melanomagenesis. Tanning bed radiation is often thought of as a substitute for natural UV radiation despite differences in the maximum doses, UV content, body sites exposed, and patterns of melanoma that arise. Methods: To better understand the epidemiologic trends and etiology of melanoma associated with tanning bed use, we described the patterns of melanoma in patients with quantifiable tanning bed usage and performed exome sequencing of 182 melanocytes from normal skin of a subset of these patients. Results: Tanning bed users were more likely than non-users to have melanoma on body sites with low cumulative levels of sun damage and were more likely to have multiple melanomas. The melanocytes in normal appearing skin from tanning bed users had higher mutation burdens, a higher proportion of melanocytes with pathogenic mutations, and distinct mutational signatures. These differences were most prominent over body sites that experience comparatively less exposure to natural sunlight. Conclusions: We conclude that tanning bed radiation induces melanoma by increasing the mutation burden of melanocytes and by mutagenizing a broader field of melanocytes than are typically exposed to natural sunlight. The unique signatures of mutations in skin cells of tanning users may be attributable to the distinct spectra of radiation emitted from solariums.

The psychosocial work environment and mental health of teachers: a comparative study between the United Kingdom and Hong Kong.

PURPOSE: There is limited research on teachers' psychosocial work environment and mental health, and most has been conducted in predominantly Western countries that share a number of important common characteristics that distinguish them from countries in many other regions of the world. Within the framework of the effort-reward imbalance (ERI) theoretical model, the relationship between the psychosocial work environment and mental health of teachers in the United Kingdom (UK) and Hong Kong (HK) was investigated. METHODS: Full-time qualified teachers from both the UK and HK (N = 259) participated in the research. They were asked to fill in a set of questionnaires that measured their perceived stress, mental health, psychosocial work environment and demographic information. RESULTS: Perceived stress was found to predict teachers' mental health. Overcommitment, the intrinsic component of the ERI model, predicted mental health among HK teachers. There were significant differences in the psychosocial variables between UK and HK teachers. CONCLUSION: The results showed support for the ERI model and in particular for the relationship between stress and mental health and demonstrated the role of overcommitment in the teaching profession. Some implications are discussed for combating cultural differences in managing the psychosocial work environment of teachers.

Public Engagement Through Shared Immersion: Participating in the Processes of Research.

Recently, the literature has emphasized the aims and logistics of public engagement, rather than its epistemic and cultural processes. In this conceptual article, we use our work on surgical simulation to describe a process that has moved from the classroom and the research laboratory into the public sphere. We propose an innovative shared immersion model for framing the relationship between engagement activities and research. Our model thus frames the public engagement experience as a participative encounter, which brings visitor and researcher together in a shared (surgical) experience mediated by experts from a range of domains.

Voice Restoration and Quality of Life in Larynx Cancer.

Voice restoration following laryngectomy has a significant influence on quality of life (QOL). Three main techniques exist to provide voice: esophageal speech (ES), artificial larynx (electrolarynx [EL]), and tracheoesophageal puncture (TEP). Although the EL was historically the most used technique, TEP has quickly become the gold standard. ES remains the least frequently used technique in developed countries. Technique selection must be made on an individual basis, considering the patient's cancer history and comorbidities. Ultimately, the choice in voice-restoration technique requires joint decision making with the surgeon, speech pathologist, and patient.

What Are You Worried About? Content and Extent of Worry in Autistic Adults.

Autistic adults commonly experience anxiety and worry, although knowledge on how worry presents and the content, extent, and experiences among autistic adults is limited. A convergent parallel mixed-methods approach was used to explore the presentation and experiences of worry in autistic and non-autistic adults. Quantitative surveys were used to compare the content and extent of worry in autistic adults to non-autistic adults, with semi-structured interviews also conducted with autistic adults to gain a deeper understanding of the experiences, impacts and content of worry in autistic adults. Findings indicated that autistic adults demonstrated clinically significant levels of worry which were substantially higher than non-autistic adults. Autistic adults described worry as a cycle of negative thoughts impacting their daily life. Findings indicate that autistic adults may worry more than non-autistic adults, impacting on participation in activities of daily living, sleep, and mental health.

Clinical and Histologic Features Associated With Malignant Transformation of Oral Cavity Dysplasia Managed at a Single North American Institution.

Importance: Reports characterizing clinical and histologic features associated with a higher risk for development of malignant lesions in the background of an oral potentially malignant disorder have largely reflected East Asian populations. Long-term studies among the North American population are rare. Objective: To evaluate risk of malignant transformation (MT) of oral dysplastic lesions by investigating the demographic, social, clinical, and histologic factors that may be associated with an increased rate as well as a decreased time to MT. Design, Setting, and Participants: This was a retrospective cohort study with medical record review at a single institution from January 1, 2000, to December 31, 2019, with follow-up for 20 years. Patients were excluded if they were younger than 18 years, the first biopsy diagnosis showed cancer, biopsies were never performed, biopsies were taken from sites outside of the oral cavity, there was no additional follow-up after the first visit, or the biopsy specimen was not characterized on the spectrum of dysplasia. Exposures: Diagnosis of leukoplakia of oral mucosa, unspecified lesions of oral mucosa, or other disturbances of oral epithelium. Main Outcomes and Measures: Main outcome measures included MT rate and time to MT as well as demographic, social, clinical, physical, and histologic features associated with MT. Results: Thirty-eight of 264 lesions (14%) in 241 patients (132 men and 109 women; mean [SD] age, 64 [13] years) underwent MT. Of the 38 lesions that underwent MT, 19 (50%) underwent transformation by 424 days, 28 (75%) by 870 days, and 34 (90%) by 1600 days. Nodularity, friability, and mass effect were more commonly observed in malignant lesions (nodularity: 42.9% vs 10.0%; difference, 32.9%; OR, 6.72; 95% CI, 3.03-14.89; friability: 42.9% vs 12.8%; difference, 30.1%; OR, 5.11; 95% CI, 1.66-15.69; mass effect: 54.2% vs 10.4%; difference, 43.8%; OR, 10.16; 95% CI, 4.12-25.09). Men were less likely than women to have multiple lesions in the oral cavity (OR, 0.40; 95% CI, 0.22-0.74). Having multiple abnormal sites was associated with higher percentage of MT (OR, 3.38; 95% CI, 1.63-7.01). Conclusions and Relevance: In this cohort study, nodularity and mass effect were associated with lesions that may push, displace, or invade surrounding tissue, and these were more likely to be present in oral dysplastic lesions that ultimately progressed to cancer. There may be less utility in continuing surveillance beyond 5 years.