From Digital Mental Health to Digital Social and Emotional Wellbeing: How Indigenous Community-Based Participatory Research Influenced the Australian Government's Digital Mental Health Agenda.

This paper describes the first six years of a government-initiated project to train Indigenous health professionals in digital mental health (d-MH). It illustrates how community-based participatory research (CBPR) methods were used to enable this "top-down" project to be transformed into a 'ground-up' community-guided process; and how, in turn, the guidance from the local Indigenous community partners went on to influence the national government's d-MH agenda. The CBPR partnership between five community partners and a university rural health department is described, with illustrations of how CBPR harnessed the community's voice in making the project relevant to their wellbeing needs. The local Indigenous community's involvement led to a number of unexpected outcomes, which impacted locally and nationally. At an early stage, the conceptual framework of the project was changed from d-MH to the culturally-relevant Indigenous framework of digital social and emotional wellbeing (d-SEWB). This led to a significant expansion of the range and type of digital resources; and to other notable outcomes such as successful advocacy for an Aboriginal-specific online therapy program and for a dedicated "one-stop-shop" d-SEWB website, Wellmob, which was funded by the Australian government in 2019-2021. Some of the implications of this project for future Indigenous CBPR projects are discussed

Community based service providers' perspectives on frequent and/or avoidable admission of older people with chronic disease in rural NSW: a qualitative study

Background: Frequent and potentially avoidable hospital admission amongst older patients with ambulatory care sensitive (ACS) chronic conditions is a major topic for research internationally, driven by the imperative to understand and therefore reduce hospital admissions. Research to date has mostly focused on analysis of routine data using ACS as a proxy for 'potentially avoidable'. There has been less research on the antecedents of frequent and/or avoidable admission from the perspectives of patients or those offering community based care and support for these patients. This study aimed to explore community based service providers' perspectives on the factors contributing to admission among older patients with chronic disease and a history of frequent and potentially avoidable admission. Methods. 15 semi-structured interviews with community based providers of health care and other services, and an emergency department physician were conducted. Summary documents were produced and thematic analysis undertaken. Results: A range of complex barriers which limit or inhibit access to services were reported. We classified these as external and internal barriers. Important external barriers included: complexity of provision of services, patients' limited awareness of different services and their inexperience in accessing services, patients needing a higher level or longer length of service than they currently have access to, or an actual lack of available services, patient poverty, rurality, and transport. Important internal barriers included: fear (of change for example), a 'stoic' attitude to life, and for some, the difficulty of accepting their changed health status. Conclusions: The factors underlying frequent and/or potentially avoidable admission are numerous and complex. Identifying strategies to improve services or interventions for this group requires understanding patient, carer and service providers' perspectives. Improving accessibility of services is also complex, and includes consideration of patients' social, emotional and psychological ability and willingness to use services as well as those services being available and easily accessed

Enzyme-Linked Immunosorbent Assay and Serologic Responses to Pneumocystis jiroveci

Seroepidemiologic studies of Pneumocystis pneumonia (PCP) in humans have been limited by inadequate reagents. We have developed an enzyme-linked immunosorbent assay (ELISA) using three overlapping recombinant fragments of the human Pneumocystis major surface glycoprotein (MsgA, MsgB, and MsgC) for analysis of antibody responses in HIV-positive patients and healthy blood donors. HIV-positive patients had significantly higher antibody levels to all Msg fragments. Furthermore, HIV-positive patients who experienced a previous episode of PCP (PCP-positive) had higher level of antibodies to MsgC than patients who never had PCP. A significant association was found between ELISA antibody level and reactivity by Western blot in HIV-positive patients, especially those who were PCP-positive. Thus, this ELISA will be useful in studying serum antibody responses to Pneumocystis in different human populations

Healthcare Worker Occupation and Immune Response to Pneumocystis jirovecii

Humans may be a reservoir for this pathogen and transmit it from person to person

Development of a National Pain Management Competency Profile to Guide Entry-Level Physiotherapy Education in Canada

Background National strategies from North America call for substantive improvements in entry-level pain management education to help reduce the burden of chronic pain. Past work has generated a valuable set of interprofessional pain management competencies to guide the education of future health professionals. However, there has been very limited work that has explored the development of such competencies for individual professions in different regions. Developing profession-specific competencies tailored to the local context is a necessary first step to integrate them within local regulatory systems. Our group is working toward this goal within the context of entry-level physiotherapy (PT) programs across Canada. Aims This study aimed to create a consensus-based competency profile for pain management, specific to the Canadian PT context. Methods A modified Delphi design was used to achieve consensus across Canadian university-based and clinical pain educators. Results Representatives from 14 entry-level PT programs (93% of Canadian programs) and six clinical educators were recruited. After two rounds, a total of 15 competencies reached the predetermined endorsement threshold (75%). Most participants (85%) reported being “very satisfied” with the process. Conclusions This process achieved consensus on a novel pain management competency profile specific to the Canadian PT context. The resulting profile delineates the necessary abilities required by physiotherapists to manage pain upon entry to practice. Participants were very satisfied with the process. This study also contributes to the emerging literature on integrated research in pain management by profiling research methodology that can be used to inform related work in other health professions and regions

Initial Evaluation of the Effects of Aerosolized Florida Red Tide Toxins (Brevetoxins) in Persons with Asthma

Florida red tides annually occur in the Gulf of Mexico, resulting from blooms of the marine dinoflagellate Karenia brevis. K. brevis produces highly potent natural polyether toxins, known as brevetoxins, that activate voltage-sensitive sodium channels. In experimental animals, brevetoxins cause significant bronchoconstriction. A study of persons who visited the beach recreationally found a significant increase in self-reported respiratory symptoms after exposure to aerosolized Florida red tides. Anecdotal reports indicate that persons with underlying respiratory diseases may be particularly susceptible to adverse health effects from these aerosolized toxins. Fifty-nine persons with physician-diagnosed asthma were evaluated for 1 hr before and after going to the beach on days with and without Florida red tide. Study participants were evaluated with a brief symptom questionnaire, nose and throat swabs, and spirometry approved by the National Institute for Occupational Safety and Health. Environmental monitoring, water and air sampling (i.e., K. brevis, brevetoxins, and particulate size distribution), and personal monitoring (for toxins) were performed. Brevetoxin concentrations were measured by liquid chromatography mass spectrometry, high-performance liquid chromatography, and a newly developed brevetoxin enzyme-linked immunosorbent assay. Participants were significantly more likely to report respiratory symptoms after Florida red tide exposure. Participants demonstrated small but statistically significant decreases in forced expiratory volume in 1 sec, forced expiratory flow between 25 and 75%, and peak expiratory flow after exposure, particularly those regularly using asthma medications. Similar evaluation during nonexposure periods did not significantly differ. This is the first study to show objectively measurable adverse health effects from exposure to aerosolized Florida red tide toxins in persons with asthma. Future studies will examine the possible chronic effects of these toxins among persons with asthma and other chronic respiratory impairment

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN