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John Canton, Kate M Scott, Paul GlueDepartment of Psychological Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New ZealandAbstract: This article proposes a number of recommendations for the treatment of generalized social phobia, based on a systematic literature review and meta-analysis. An optimal treatment regimen would include a combination of medication and psychotherapy, along with an assertive clinical management program. For medications, selective serotonin reuptake inhibitors and dual serotonin-norepinephrine reuptake inhibitors are first-line choices based on their efficacy and tolerability profiles. The nonselective monoamine oxidase inhibitor, phenelzine, may be more potent than these two drug classes, but because of its food and drug interaction liabilities, its use should be restricted to patients not responding to selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors. There are other medication classes with demonstrated efficacy in social phobia (benzodiazepines, antipsychotics, alpha-2-delta ligands), but due to limited published clinical trial data and the potential for dependence and withdrawal issues with benzodiazepines, it is unclear how best to incorporate these drugs into treatment regimens. There are very few clinical trials on the use of combined medications. Cognitive behavior therapy appears to be more effective than other evidence-based psychological techniques, and its effects appear to be more enduring than those of pharmacotherapy. There is some evidence, albeit limited to certain drug classes, that the combination of medication and cognitive behavior therapy may be more effective than either strategy used alone. Generalized social phobia is a chronic disorder, and many patients will require long-term support and treatment.Keywords: social phobia, social anxiety disorder, psychotherapy, cognitive behavior therapy, antidepressant

Background: A simple prognostic model was previously developed to predict the probability of recently-diagnosed patients reaching negative outcomes (postural instability, dementia or death) in a 5-year period., Objectives: To validate this model in an independent cohort and establish utility at later time points., Methods: Validation was performed using data collected in an incident cohort at baseline, 2 and 4 years. Predicted negative outcome probabilities were compared to actual 5-year outcomes., Results: The model, based on age, MDS-UPDRS axial score and 60-second animal fluency, predicted poor 5-year outcome when applied at baseline, (area under the curve (AUC) 0.80), 2 years (AUC 0.82) and 4 years (AUC 0.71). Power calculations showed that selecting a subgroup with prognostic score >0.5 reduced the sample size required for a disease-modifying trial., Conclusions: This 5-year prognostic model has good accuracy when employed up to 4 years from diagnosis and may help stratification for disease-modifying trials., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Autotrophic bacteria are able to fix CO 2 in a great diversity of habitats, even though this dissolved gas is relatively scarce at neutral pH and above. As many of these bacteria rely on CO 2 fixation by ribulose 1,5-bisphospate carboxylase/oxygenase (RubisCO) for biomass generation, they must compensate for the catalytical constraints of this enzyme with CO 2 -concentrating mechanisms (CCMs). CCMs consist of CO 2 and HCO 3 - transporters and carboxysomes. Carboxysomes encapsulate RubisCO and carbonic anhydrase (CA) within a protein shell and are essential for the operation of a CCM in autotrophic Bacteria that use the Calvin-Benson-Basham cycle. Members of the genus Thiomicrospira lack genes homologous to those encoding previously described CA, and prior to this work, the mechanism of function for their carboxysomes was unclear. In this paper, we provide evidence that a member of the recently discovered iota family of carbonic anhydrase enzymes (ιCA) plays a role in CO 2 fixation by carboxysomes from members of Thiomicrospira and potentially other Bacteria . Carboxysome enrichments from Thiomicrospira pelophila and Thiomicrospira aerophila were found to have CA activity and contain ιCA, which is encoded in their carboxysome loci. When the gene encoding ιCA was interrupted in T. pelophila , cells could no longer grow under low-CO 2 conditions, and CA activity was no longer detectable in their carboxysomes. When T. pelophila ιCA was expressed in a strain of Escherichia coli lacking native CA activity, this strain recovered an ability to grow under low CO 2 conditions, and CA activity was present in crude cell extracts prepared from this strain., Importance: Here, we provide evidence that iota carbonic anhydrase (ιCA) plays a role in CO 2 fixation by some organisms with CO 2 -concentrating mechanisms; this is the first time that ιCA has been detected in carboxysomes. While ιCA genes have been previously described in other members of bacteria, this is the first description of a physiological role for this type of carbonic anhydrase in this domain. Given its distribution in alkaliphilic autotrophic bacteria, ιCA may provide an advantage to organisms growing at high pH values and could be helpful for engineering autotrophic organisms to synthesize compounds of industrial interest under alkaline conditions., Competing Interests: The authors declare no conflict of interest.

Background: Adolescence is a key developmental period that affects lifelong health and is impacted by adolescents regularly engaging with digital health information. Adolescents need digital health literacy (DHL) to effectively evaluate the quality and credibility of such information, and to navigate an increasingly complex digital health environment. Few educational resources exist to improve DHL, and few have involved adolescents during design. The co-design approach may hold utility through developing interventions with participants as design partners., Objective: This project aimed to explore the co-design approach in developing an educational resource to improve adolescents' DHL., Methods: Adolescents (12-17 years old) attended 4 interactive co-design workshops (June 2021-April 2022). Participant perspectives were gathered on DHL and the design of educational resources to improve it. Data generated were analyzed through content analysis to inform educational resource development., Results: In total, 27 participants from diverse backgrounds attended the workshops. Insight was gained into participants' relationship with digital health information, including acceptance of its benefits and relevance, coupled with awareness of misinformation issues, revealing areas of DHL need. Participants provided suggestions for educational resource development that incorporated the most useful aspects of digital formats to develop skills across these domains. The following 4 themes were derived from participant perspectives: ease of access to digital health information, personal and social factors that impacted use, impacts of the plethora of digital information, and anonymity offered by digital sources. Initial participant evaluation of the developed educational resource was largely positive, including useful suggestions for improvement., Conclusions: Co-design elicited and translated authentic adolescent perspectives and design ideas into a functional educational resource. Insight into adolescents' DHL needs generated targeted educational resource content, with engaging formats, designs, and storylines. Co-design holds promise as an important and empowering tool for developing interventions to improve adolescents' DHL., (©Callum C Lewis, Melody Taba, Tiffany B Allen, Patrina HY Caldwell, S Rachel Skinner, Melissa Kang, Hamish Henderson, Liam Bray, Madeleine Borthwick, Philippa Collin, Kirsten McCaffery, Karen M Scott. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 07.08.2024.)

Background: Healthcare workplace mistreatment has been documented globally. Poor workplace behaviour, ranging from incivility to bullying and harassment, is common in healthcare, and contributes significantly to adverse events in healthcare, poor mental health among healthcare workers, and to attrition in the healthcare workforce, particularly in junior years. Poor workplace behaviour is often normalised, and is difficult to address. Verbatim theatre, a form of research informed theatre in which plays are created from informants' exact words only, is particularly suited to facilitating workplace culture change by raising awareness about issues that are difficult to discuss. The objective of this study was to assess the impact of the verbatim theatre play 'Grace Under Pressure' on workplace culture in NSW hospitals., Methods: The intervention was conducted in 13 hospitals from 8 Local Health Districts (LHDs) in NSW, Australia, in October and November 2019, with aggregated impact across all sites measured by a bespoke survey ('Pam McLean Centre (PMC) survey') at the conclusion of the intervention. This study was conducted in 3 Local Health Districts (one urban, one regional, one remote), with data collection conducted in November-December 2019 and December 2020. The study design was a mixed methods assessment of the play's impact using (1) validated baseline measures of psychosocial risk, analysed descriptively, (2) overall findings from the PMC survey above, analysed descriptively, (3) interviews conducted within a month of the intervention, analysed thematically and (4) interviews conducted one year later, analysed thematically., Results: Half (51.5%) of the respondents (n = 149) to the baseline survey had scores indicating high risk of job strain and depressive symptoms. Of 478 respondents to the PMC survey (response rate 57%), 93% found the play important, 92% recommended others see the play, 89% considered that it stimulated thinking about workplace behaviour, and 85% that it made discussing these issues easier. Thematic analysis of interviews within one month (n = 21) showed that the play raised awareness about poor workplace behaviour and motivated behaviour change. Interviews conducted one year later (n = 6) attributed improved workplace culture to the intervention due to improved awareness, discussion and capacity to respond to challenging issues., Conclusions: Verbatim theatre is effective in raising awareness about difficult workplace behaviour in ways that motivate behaviour change, and hence can be effective in catalysing real improvements in healthcare workplace culture. Creative approaches are recommended for addressing similarly complex challenges in healthcare workforce retention., (© 2024. The Author(s).)

Background: Cardiovascular disease (CVD) represents the greatest burden of mortality worldwide, and statins are the most commonly prescribed drug in its management. A wealth of information pertaining to statins and their side effects is on the internet; however, to date, no assessment of the accuracy, credibility, and readability of this information has been undertaken., Objective: This study aimed to evaluate the quality (accuracy, credibility, and readability) of websites likely to be visited by the general public undertaking a Google search of the side effects and use of statin medications., Methods: Following a Google web search, we reviewed the top 20 consumer-focused websites with statin information. Website accuracy, credibility, and readability were assessed based on website category (commercial, not-for-profit, and media), website rank, and the presence or absence of the Health on the Net Code of Conduct (HONcode) seal. Accuracy and credibility were assessed following the development of checklists (with 20 and 13 items, respectively). Readability was assessed using the Simple Measure of Gobbledegook scores., Results: Overall, the accuracy score was low (mean 14.35 out of 20). While side effects were comprehensively covered by 18 websites, there was little information about statin use in primary and secondary prevention. None of the websites met all criteria on the credibility checklist (mean 7.8 out of 13). The median Simple Measure of Gobbledegook score was 9.65 (IQR 8.825-10.85), with none of the websites meeting the recommended reading grade of 6, even the media websites. A website bearing the HONcode seal did not mean that the website was more comprehensive or readable., Conclusions: The quality of statin-related websites tended to be poor. Although the information contained was accurate, it was not comprehensive and was presented at a reading level that was too difficult for an average reader to fully comprehend. As such, consumers risk being uninformed about this pharmacotherapy., (©Eunice Ling, Domenico de Pieri, Evenne Loh, Karen M Scott, Stephen C H Li, Heather J Medbury. Originally published in the Interactive Journal of Medical Research (https://www.i-jmr.org/), 14.03.2024.)

Background: Mental health service providers are increasingly interested in patient perspectives. We examined rates and predictors of patient-reported satisfaction and perceived helpfulness in a cross-national general population survey of adults with 12-month DSM-IV disorders who saw a provider for help with their mental health., Methods: Data were obtained from epidemiological surveys in the World Mental Health Survey Initiative. Respondents were asked about satisfaction with treatments received from up to 11 different types of providers (very satisfied, satisfied, neither satisfied nor dissatisfied, somewhat dissatisfied, very dissatisfied) and helpfulness of the provider (a lot, some, a little, not at all). We modelled predictors of satisfaction and helpfulness using a dataset of patient-provider observations (n = 5,248)., Results: Most treatment was provided by general medical providers (37.4%), psychiatrists (18.4%) and psychologists (12.7%). Most patients were satisfied or very satisfied (65.9-87.5%, across provider) and helped a lot or some (64.4-90.3%). Spiritual advisors and healers were most often rated satisfactory and helpful. Social workers in human services settings were rated lowest on both dimensions. Patients also reported comparatively low satisfaction with general medical doctors and psychiatrists/psychologists and found general medical doctors less helpful than other providers. Men and students reported lower levels of satisfaction than women and nonstudents. Respondents with high education reported higher satisfaction and helpfulness than those with lower education. Type of mental disorder was unrelated to satisfaction but in some cases (depression, bipolar spectrum disorder, social phobia) was associated with low perceived helpfulness. Insurance was unrelated to either satisfaction or perceived helpfulness but in some cases was associated with elevated perceived helpfulness for a given level of satisfaction., Conclusions: Satisfaction with and perceived helpfulness of treatment varied as a function of type of provider, service setting, mental status, and socio-demographic variables. Invariably, caution is needed in combining data from multiple countries where there are cultural and service delivery variations. Even so, our findings underscore the utility of patient perspectives in treatment evaluation and may also be relevant in efforts to match patients to treatments., (© 2024. The Author(s).)

Using dissolved inorganic carbon (DIC) as a major carbon source, as autotrophs do, is complicated by the bedeviling nature of this substance. Autotrophs using the Calvin-Benson-Bassham cycle (CBB) are known to make use of a toolkit comprised of DIC transporters and carbonic anhydrase enzymes (CA) to facilitate DIC fixation. This minireview provides a brief overview of the current understanding of how toolkit function facilitates DIC fixation in Cyanobacteria and some Proteobacteria using the CBB and continues with a survey of the DIC toolkit gene presence in organisms using different versions of the CBB and other autotrophic pathways (reductive citric acid cycle, Wood-Ljungdahl pathway, hydroxypropionate bicycle, hydroxypropionate-hydroxybutyrate cycle, and dicarboxylate-hydroxybutyrate cycle). The potential function of toolkit gene products in these organisms is discussed in terms of CO 2 and HCO 3 - supply from the environment and demand by the autotrophic pathway. The presence of DIC toolkit genes in autotrophic organisms beyond those using the CBB suggests the relevance of DIC metabolism to these organisms and provides a basis for better engineering of these organisms for industrial and agricultural purposes., Competing Interests: The authors declare no conflict of interest.

Three-dimensional (3D) printing is increasingly used in medical education and paediatric cardiology. A technology-enhanced learning (TEL) module was designed to accompany 3D printed models of congenital heart disease (CHD) to aid in the teaching of medical students. There are few studies evaluating the attitudes and perceptions of medical students regarding their experience of learning about CHD using 3D printing. This study aimed to explore senior medical students' experiences in learning about paediatric cardiology through a workshop involving 3D printed models of CHD supported by TEL in the form of online case-based learning. A mixed-methods evaluation was undertaken involving a post-workshop questionnaire ( n  = 94 students), and focus groups ( n  = 16 students). Focus group and free-text questionnaire responses underwent thematic analysis. Questionnaire responses demonstrated widespread user satisfaction; 91 (97%) students agreed that the workshop was a valuable experience. The highest-level satisfaction was for the physical 3D printed models, the clinical case-based learning, and opportunity for peer collaboration. Thematic analysis identified five key themes: a variable experience of prior learning, interplay between physical and online models, flexible and novel workshop structure, workshop supported the learning outcomes, and future opportunities for learning using 3D printing. A key novel finding was that students indicated the module increased their confidence to teach others about CHD and recommended expansion to other parts of the curriculum. 3D printed models of CHD are a valuable learning resource and contribute to the richness and enjoyment of medical student learning, with widespread satisfaction., Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01840-w., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© Crown 2023.)

The traditional story of the evolution of the horse (family Equidae) has been in large part about the evolution of their feet. How did modern horses come to have a single toe (digit III), with the hoof bearing a characteristic V-shaped keratinous frog on the sole, and what happened to the other digits? While it has long been known that the proximal portions of digits II and IV are retained as the splint bones, a recent hypothesis suggested that the distal portion of these digits have also been retained as part of the frog, drawing upon the famous Laetoli footprints of the tridactyl (three-toed) equid Hipparion as part of the evidence. We show here that, while there is good anatomical and embryological evidence for the proximal portions of all the accessory digits (i.e. I and V, as well as II and IV) being retained in the feet of modern horses, evidence is lacking for the retention of any distal portions of these digits. There is also good ichnological evidence that many tridactyl equids possessed a frog, and that the frog has been part of the equid foot for much of equid evolutionary history., Competing Interests: We declare we have no competing interests., (© 2023 The Authors.)

Importance: Understanding the association of civil violence with mental disorders is important for developing effective postconflict recovery policies., Objective: To estimate the association between exposure to civil violence and the subsequent onset and persistence of common mental disorders (in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]) in representative surveys of civilians from countries that have experienced civil violence since World War II., Design, Setting, and Participants: This study used data from cross-sectional World Health Organization World Mental Health (WMH) surveys administered to households between February 5, 2001, and January 5, 2022, in 7 countries that experienced periods of civil violence after World War II (Argentina, Colombia, Lebanon, Nigeria, Northern Ireland, Peru, and South Africa). Data from respondents in other WMH surveys who immigrated from countries with civil violence in Africa and Latin America were also included. Representative samples comprised adults (aged ≥18 years) from eligible countries. Data analysis was performed from February 10 to 13, 2023., Exposures: Exposure was defined as a self-report of having been a civilian in a war zone or region of terror. Related stressors (being displaced, witnessing atrocities, or being a combatant) were also assessed. Exposures occurred a median of 21 (IQR, 12-30) years before the interview., Main Outcomes and Measures: The main outcome was the retrospectively reported lifetime prevalence and 12-month persistence (estimated by calculating 12-month prevalence among lifetime cases) of DSM-IV anxiety, mood, and externalizing (alcohol use, illicit drug use, or intermittent explosive) disorders., Results: This study included 18 212 respondents from 7 countries. Of these individuals, 2096 reported that they were exposed to civil violence (56.5% were men; median age, 40 [IQR, 30-52] years) and 16 116 were not exposed (45.2% were men; median age, 35 [IQR, 26-48] years). Respondents who reported being exposed to civil violence had a significantly elevated onset risk of anxiety (risk ratio [RR], 1.8 [95% CI, 1.5-2.1]), mood (RR, 1.5 [95% CI, 1.3-1.7]), and externalizing (RR, 1.6 [95% CI, 1.3-1.9]) disorders. Combatants additionally had a significantly elevated onset risk of anxiety disorders (RR, 2.0 [95% CI, 1.3-3.1]) and refugees had an increased onset risk of mood (RR, 1.5 [95% CI, 1.1-2.0]) and externalizing (RR, 1.6 [95% CI, 1.0-2.4]) disorders. Elevated disorder onset risks persisted for more than 2 decades if conflicts persisted but not after either termination of hostilities or emigration. Persistence (ie, 12-month prevalence among respondents with lifetime prevalence of the disorder), in comparison, was generally not associated with exposure., Conclusions: In this survey study of exposure to civil violence, exposure was associated with an elevated risk of mental disorders among civilians for many years after initial exposure. These findings suggest that policy makers should recognize these associations when projecting future mental disorder treatment needs in countries experiencing civil violence and among affected migrants.

Bird-building collisions are a major source of wild bird mortality, with hundreds of millions of fatalities each year in the United States and Canada alone. Here, we use two decades of daily citizen science monitoring to characterize day-to-day variation in building collisions and determine the factors that predict the highest risk times in two North American cities. We use these analyses to evaluate three potential causes of increased collision risk: heightened migration traffic during benign weather, increased navigational and flight errors during inclement weather, and increased errors in response to highly directional sunlight that enhances reflected images. The seasonal phenology of collisions was consistent across sites and years, with daily collision rates approximately twofold higher in autumn as compared to spring. During both migration seasons, collision risk was best predicted by the weather conditions at dawn. In spring, peak collision risk occurs on days with warm temperatures, south winds, and a lack of precipitation at dawn. In autumn, peak collision occurs on days with cool temperatures, north winds, high atmospheric pressure, a lack of precipitation, and clear conditions with high visibility. Based on these results, we hypothesize that collisions are influenced by two main weather-driven mechanisms. First, benign weather at dawn and winds that are favorable for migration cause an increase in migration traffic in both spring and autumn, creating greater opportunity for collisions to occur. Second, for autumnal migrants, cold clear conditions may cause an additional increase in collision risk. We propose that these conditions may be particularly hazardous in autumn because of the high abundance of naïve and diurnal migrants at that time of year. Our analysis also establishes that a relatively small proportion of days (15%) are responsible for 50% of the total collision mortality within a season, highlighting the importance of targeting mitigation strategies to the most hazardous times., Competing Interests: We have no competing interests., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Inflammation contributes to Parkinson's disease pathogenesis. We hypothesized that B lymphocytes are involved in Parkinson's disease progression. We measured antibodies to alpha-synuclein and tau in serum from patients with rapid eye movement sleep behaviour disorder ( n = 79), early Parkinson's disease ( n = 50) and matched controls ( n = 50). Rapid eye movement sleep behaviour disorder cases were stratified by risk of progression to Parkinson's disease (low risk = 30, high risk = 49). We also measured B-cell activating factor of the tumour necrosis factor receptor family, C-reactive protein and total immunoglobulin G. We found elevated levels of antibodies to alpha-synuclein fibrils in rapid eye movement sleep behaviour disorder patients at high risk of Parkinson's disease conversion (ANOVA, P < 0.001) and lower S129D peptide-specific antibodies in those at low risk (ANOVA, P < 0.001). An early humoral response to alpha-synuclein is therefore detectable prior to the development of Parkinson's disease. Peripheral B lymphocyte phenotyping using flow cytometry in early Parkinson's disease patients and matched controls ( n = 41 per group) revealed reduced B cells in Parkinson's disease, particularly in those at higher risk of developing an early dementia [ t (3) = 2.87, P = 0.01]. Patients with a greater proportion of regulatory B cells had better motor scores [ F (4,24) = 3.612, P = 0.019], suggesting they have a protective role in Parkinson's disease. In contrast, B cells isolated from Parkinson's disease patients at higher risk of dementia had greater cytokine (interleukin 6 and interleukin 10) responses following in vitro stimulation. We assessed peripheral blood lymphocytes in alpha-synuclein transgenic mouse models of Parkinson's disease: they also had reduced B cells, suggesting this is related to alpha-synuclein pathology. In a toxin-based mouse model of Parkinson's disease, B-cell deficiency or depletion resulted in worse pathological and behavioural outcomes, supporting the conclusion that B cells play an early protective role in dopaminergic cell loss. In conclusion, we found changes in the B-cell compartment associated with risk of disease progression in rapid eye movement sleep behaviour disorder (higher alpha-synuclein antibodies) and early Parkinson's disease (lower levels of B lymphocytes that were more reactive to stimulation). Regulatory B cells play a protective role in a mouse model, potentially by attenuating inflammation and dopaminergic cell loss. B cells are therefore likely to be involved in the pathogenesis of Parkinson's disease, albeit in a complex way, and thus warrant consideration as a therapeutic target., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: 3D printing has recently emerged as an alternative to cadaveric models in medical education. A growing body of research supports the use of 3D printing in this context and details the beneficial educational outcomes. Prevailing studies rely on participants' stated preferences, but little is known about actual student preferences., Methods: A mixed methods approach, consisting of structured observation and computer vision, was used to investigate medical students' preferences and handling patterns when using 3D printed versus cadaveric models in a cardiac pathology practical skills workshop. Participants were presented with cadaveric samples and 3D printed replicas of congenital heart deformities., Results: Analysis with computer vision found that students held cadaveric hearts for longer than 3D printed models (7.71 vs. 6.73 h), but this was not significant when comparing across the four workshops. Structured observation found that student preferences changed over the workshop, shifting from 3D printed to cadaveric over time. Interactions with the heart models (e.g., pipecleaners) were comparable., Conclusion: We found that students had a slight preference for cadaveric hearts over 3D printed hearts. Notably, our study contrasts with other studies that report student preferences for 3D printed learning materials. Given the relative equivalence of the models, there is opportunity to leverage 3D printed learning materials (which are not scarce, unlike cadaveric materials) to provide equitable educational opportunities (e.g., in rural settings, where access to cadaveric hearts is less likely)., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) under exclusive licence to International Association of Medical Science Educators 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Transfection of chondrocytes with microRNA-451(miR-451), present in growth zone cartilage of the growth plate, upregulates production of enzymes association with extracellular matrix degradation. miR-451 is also present in articular cartilage and exacerbates IL-1β effects in articular chondrocytes. Moreover, when osteoarthritis (OA) was induced in Sprague Dawley rats via bilateral anterior cruciate ligament transection (ACLT), miR-451 expression was increased in OA cartilage compared to control, suggesting its inhibition might be used to prevent or treat OA. To examine the prophylactic and therapeutic potential of inhibiting miR-451, we evaluated treatment with miR-451 power inhibitor (451-PI) at the onset of joint trauma and treatment after OA had developed. The prophylactic animal cohort received twice-weekly intra-articular injections of either 451-PI or a negative control (NC-PI) beginning on post-surgical day 3. OA was allowed to develop for 24 days in the therapeutic cohort before beginning injections. All rats were killed on day 45. Micro-CT, histomorphometrics, OARSI scoring, and muscle force testing were performed on samples. 451-PI mitigated OA progression compared to NC-PI limbs in the prophylactic cohort based on histomorphometric analysis and OARSI scoring, but no differences were detected by micro-CT. 451-PI treatment beginning 24 days post-surgery was not able to reduce OA severity. Prophylactic administration of 451-PI mitigates OA progression in a post-trauma ACLT rat model supporting its potential to prevent OA development following an ACLT injury clinically., (© 2022. The Author(s).)

Background: The internet and social media are increasingly popular sources of health information for adolescents. Using online health information requires digital health literacy, consisting of literacy, analytical skills and personal capabilities such as self-efficacy. Appraising trustworthiness and relevance of online health information requires critical health literacy to discriminate between sources, critically analyse meaning and relevance, and use information for personal health. Adolescents with poor digital health literacy risk using misinformation, with potential negative health outcomes. We aimed to understand adolescents' contemporary digital health literacy and compared self-efficacy with capability., Methods: Adolescents (12-17 years) completed an eHEALS self-report digital health literacy measure, a practical search task using a think-aloud protocol and an interview to capture perceived and actual digital health literacy. eHEALS scores were generated using descriptive statistics, search tasks were analysed using an observation checklist and interviews were thematically analysed based on Social Cognitive Theory, focussing on self-efficacy., Results: Twenty-one participants generally had high self-efficacy using online health information but perceived their digital health literacy to be higher than demonstrated. They accessed online health information unintentionally on social media and intentionally via search engines. They appraised information medium, source and content using general internet searching heuristics taught at school. Information on social media was considered less trustworthy than websites, but participants used similar appraisal strategies for both; some search/appraisal heuristics were insufficiently nuanced for digital health information, sometimes resulting in misplaced trust or diminished self-efficacy. Participants felt anxious or relieved after finding online health information, depending on content, understanding and satisfaction. They did not act on information without parental and/or health professional advice. They rarely discussed findings with health professionals but would welcome discussions and learning how to find and appraise online health information., Conclusions: Whilst adolescents possess many important digital health literacy skills and generally feel self-efficacious in using them, their critical health literacy needs improving. Adolescents desire increased digital health literacy so they can confidently appraise health information they find online and on social media. Co-designed educational interventions with adolescents and health providers are required., (© 2022. The Author(s).)

Patient-reported helpfulness of treatment is an important indicator of quality in patient-centered care. We examined its pathways and predictors among respondents to household surveys who reported ever receiving treatment for major depression, generalized anxiety disorder, social phobia, specific phobia, post-traumatic stress disorder, bipolar disorder, or alcohol use disorder. Data came from 30 community epidemiological surveys - 17 in high-income countries (HICs) and 13 in low- and middle-income countries (LMICs) - carried out as part of the World Health Organization (WHO)'s World Mental Health (WMH) Surveys. Respondents were asked whether treatment of each disorder was ever helpful and, if so, the number of professionals seen before receiving helpful treatment. Across all surveys and diagnostic categories, 26.1% of patients (N=10,035) reported being helped by the very first professional they saw. Persisting to a second professional after a first unhelpful treatment brought the cumulative probability of receiving helpful treatment to 51.2%. If patients persisted with up through eight professionals, the cumulative probability rose to 90.6%. However, only an estimated 22.8% of patients would have persisted in seeing these many professionals after repeatedly receiving treatments they considered not helpful. Although the proportion of individuals with disorders who sought treatment was higher and they were more persistent in HICs than LMICs, proportional helpfulness among treated cases was no different between HICs and LMICs. A wide range of predictors of perceived treatment helpfulness were found, some of them consistent across diagnostic categories and others unique to specific disorders. These results provide novel information about patient evaluations of treatment across diagnoses and countries varying in income level, and suggest that a critical issue in improving the quality of care for mental disorders should be fostering persistence in professional help-seeking if earlier treatments are not helpful., (© 2022 World Psychiatric Association.)

Introduction: New Zealand (NZ) has a persistently high rate of suicide, particularly among young people. Hospital presentation for self-harm (SH) is one of the strongest predictors of death by suicide. Improving the monitoring of SH and suicide is a key recommendation for suicide prevention by WHO. This study will establish the first ever sentinel surveillance for SH at several large hospitals and a monthly survey of all practicing paediatricians in NZ. The study will provide robust information about the epidemiology of SH, factors associated with SH and the types of interventions required for those presenting to hospital with SH., Method and Analysis: This observational study will establish SH surveillance in the emergency departments of three public hospitals for the first time in NZ, where study population will include individuals of all ages who present with SH or suicidal ideation. The study methodology is in line with the WHO Best Practice guidelines and international collaborators in Australia and Europe. Electronic triage records will be reviewed manually by the research team to identify potential cases that meet inclusion criteria. For all eligible cases, variables of interest will be extracted from routine clinical records by the research team and recorded on a secure web-based survey application. Additionally, SH surveillance data for the national paediatric population (<15 years) will be obtained via the New Zealand Paediatric Surveillance Unit (NZPSU); paediatricians will report on included cases using the same variables using a secure survey application. A deidentified dataset will be produced for aggregated statistical analysis., Ethics and Dissemination: The University of Otago Health Ethics Committee granted ethical approval for this study in addition to local ethics approval at participating hospital sites. The study findings will be disseminated to relevant stakeholders in NZ, in addition to international audiences through publications in peer-reviewed scientific journals and conference presentations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Carboxysomes, responsible for a substantial fraction of CO 2 fixation on Earth, are proteinaceous microcompartments found in many autotrophic members of domain Bacteria , primarily from the phyla Proteobacteria and Cyanobacteria . Carboxysomes facilitate CO 2 fixation by the Calvin-Benson-Bassham (CBB) cycle, particularly under conditions where the CO 2 concentration is variable or low, or O 2 is abundant. These microcompartments are composed of an icosahedral shell containing the enzymes ribulose 1,5-carboxylase/oxygenase (RubisCO) and carbonic anhydrase. They function as part of a CO 2 concentrating mechanism, in which cells accumulate HCO 3 - in the cytoplasm via active transport, HCO 3 - enters the carboxysomes through pores in the carboxysomal shell proteins, and carboxysomal carbonic anhydrase facilitates the conversion of HCO 3 - to CO 2 , which RubisCO fixes. Two forms of carboxysomes have been described: α-carboxysomes and β-carboxysomes, which arose independently from ancestral microcompartments. The α-carboxysomes present in Proteobacteria and some Cyanobacteria have shells comprised of four types of proteins [CsoS1 hexamers, CsoS4 pentamers, CsoS2 assembly proteins, and α-carboxysomal carbonic anhydrase (CsoSCA)], and contain form IA RubisCO (CbbL and CbbS). In the majority of cases, these components are encoded in the genome near each other in a gene locus, and transcribed together as an operon. Interestingly, genome sequencing has revealed some α-carboxysome loci that are missing genes encoding one or more of these components. Some loci lack the genes encoding RubisCO, others lack a gene encoding carbonic anhydrase, some loci are missing shell protein genes, and in some organisms, genes homologous to those encoding the carboxysome-associated carbonic anhydrase are the only carboxysome-related genes present in the genome. Given that RubisCO, assembly factors, carbonic anhydrase, and shell proteins are all essential for carboxysome function, these absences are quite intriguing. In this review, we provide an overview of the most recent studies of the structural components of carboxysomes, describe the genomic context and taxonomic distribution of atypical carboxysome loci, and propose functions for these variants. We suggest that these atypical loci are JEEPs, which have modified functions based on the presence of Just Enough Essential Parts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sutter, Kerfeld and Scott.)

People with mental health and substance use issues (tāngata whai ora katoa), regardless of ethnicity, are much more likely to be hospitalised or die from COVID-19 and were identified as a priority population (Priority Group 3) in Aotearoa New Zealand's vaccination roll-out plan. Data released by the Ministry of Health show that, despite tāngata whai ora katoa being a priority group, their vaccination rates are well below those of the general population. These inequities are pronounced for Māori with mental health and addiction issues (tāngata whai ora Māori). This is not acceptable. To support tāngata whai ora physical health and wellbeing, the onus is on all of us in the health system to actively reach out, have conversations, be supportive and provide accessible vaccination for people with mental health and addiction issues. Urgent action is needed. Now is the time to ensure tāngata whai ora katoa can be equally well., Competing Interests: The authors are part of Aotearoa Equally Well, an evidence-informed collaborative taking action across the health and health-related systems to achieve physical health equity for people who experience mental health and addiction issues.