The alpha-1A adrenergic receptor regulates mitochondrial oxidative metabolism in the mouse heart.

AIMS: The sympathetic nervous system regulates numerous critical aspects of mitochondrial function in the heart through activation of adrenergic receptors (ARs) on cardiomyocytes. Mounting evidence suggests that α1-ARs, particularly the α1A subtype, are cardioprotective and may mitigate the deleterious effects of chronic ß-AR activation by shared ligands. The mechanisms underlying these adaptive effects remain unclear. Here, we tested the hypothesis that α1A-ARs adaptively regulate cardiomyocyte oxidative metabolism in both the uninjured and infarcted heart. METHODS: We used high resolution respirometry, fatty acid oxidation (FAO) enzyme assays, substrate-specific electron transport chain (ETC) enzyme assays, transmission electron microscopy (TEM) and proteomics to characterize mitochondrial function comprehensively in the uninjured hearts of wild type and α1A-AR knockout mice and defined the effects of chronic ß-AR activation and myocardial infarction on selected mitochondrial functions. RESULTS: We found that isolated cardiac mitochondria from α1A-KO mice had deficits in fatty acid-dependent respiration, FAO, and ETC enzyme activity. TEM revealed abnormalities of mitochondrial morphology characteristic of these functional deficits. The selective α1A-AR agonist A61603 enhanced fatty-acid dependent respiration, fatty acid oxidation, and ETC enzyme activity in isolated cardiac mitochondria. The ß-AR agonist isoproterenol enhanced oxidative stress in vitro and this adverse effect was mitigated by A61603. A61603 enhanced ETC Complex I activity and protected contractile function following myocardial infarction. CONCLUSIONS: Collectively, these novel findings position α1A-ARs as critical regulators of cardiomyocyte metabolism in the basal state and suggest that metabolic mechanisms may underlie the protective effects of α1A-AR activation in the failing heart.

An analysis of published study designs in PubMed prisoner health abstracts from 1963 to 2023: a text mining study.

BACKGROUND: The challenging nature of studies with incarcerated populations and other offender groups can impede the conduct of research, particularly that involving complex study designs such as randomised control trials and clinical interventions. Providing an overview of study designs employed in this area can offer insights into this issue and how research quality may impact on health and justice outcomes. METHODS: We used a rule-based approach to extract study designs from a sample of 34,481 PubMed abstracts related to epidemiological criminology published between 1963 and 2023. The results were compared against an accepted hierarchy of scientific evidence. RESULTS: We evaluated our method in a random sample of 100 PubMed abstracts. An F1-Score of 92.2% was returned. Of 34,481 study abstracts, almost 40.0% (13,671) had an extracted study design. The most common study design was observational (37.3%; 5101) while experimental research in the form of trials (randomised, non-randomised) was present in 16.9% (2319). Mapped against the current hierarchy of scientific evidence, 13.7% (1874) of extracted study designs could not be categorised. Among the remaining studies, most were observational (17.2%; 2343) followed by systematic reviews (10.5%; 1432) with randomised controlled trials accounting for 8.7% (1196) of studies and meta-analysis for 1.4% (190) of studies. CONCLUSIONS: It is possible to extract epidemiological study designs from a large-scale PubMed sample computationally. However, the number of trials, systematic reviews, and meta-analysis is relatively small - just 1 in 5 articles. Despite an increase over time in the total number of articles, study design details in the abstracts were missing. Epidemiological criminology still lacks the experimental evidence needed to address the health needs of the marginalized and isolated population that is prisoners and offenders.

Development of a palliative paramedicine framework to standardise best practice: A Delphi study.

BACKGROUND: Growing global demand for palliative care services has prompted generalist clinicians to provide adjunct support to specialist teams. Paramedics are uniquely placed to respond to these patients in the community. However, embedding palliative care principles into their core business will require multifactorial interventions at structural, healthcare service and individual clinician and consumer levels. AIM: To develop a palliative paramedicine framework suitable for national implementation, to standardise best practice in Australia. DESIGN: Delphi study utilising questionnaire completion; each round informed the need for, and content of, the next round. Free text comments were also sought in Round 1. Two rounds of Delphi were undertaken. SETTING/PARTICIPANTS: Sixty-eight participants took part in Round 1, representing six countries, and 66 in Round 2. Participants included paramedics, palliative care doctors and nurses, general practitioners, researchers and carers with lived experience and expertise in palliative paramedicine. RESULTS: Seventeen of the original 24 components gained consensus; 6 components were modified; and 9 new components arose from Round 1. All modified and new components gained consensus in Round 2. Only one original component did not gain consensus across both rounds and was excluded from the final 32-component framework. CONCLUSION: This study has developed a comprehensive national framework addressing the macro-, meso- and micro-level interventions required to standardise palliative paramedicine across Australia. Future research ought to engage a multidisciplinary team to create an implementation strategy, addressing any perceived barriers, facilitators and challenges for applying the framework into policy and practice.

'It breaks a narrative of paramedics, that we're lifesavers': A qualitative study of health professionals', bereaved family members' and carers' perceptions and experiences of palliative paramedicine.

BACKGROUND: Paramedic practice is diversifying to accommodate evolving global health trends, including community paramedicine models and growing expertise in palliative and end-of-life care. However, despite palliative care specific clinical practice guidelines and existing training, paramedics still lack the skills, confidence and clinical support to provide this type of care. AIM: To elicit paramedics', palliative care doctors and nurses', general practitioners', residential aged care nurses' and bereaved families and carers' experiences, perspectives, and attitudes on the role, barriers and enablers of paramedics delivering palliative and end-of-life care in community-based settings. DESIGN: A qualitative study employing reflexive thematic analysis of data collected from semi-structured online interviews was utilised. SETTING/PARTICIPANTS: A purposive sample of 50 stakeholders from all Australian jurisdictions participated. RESULTS: Five themes were identified: positioning the paramedic (a dichotomy between the life saver and community responder); creating an identity (the trusted clinician in a crisis), fear and threat (feeling afraid of caring for the dying), permission to care (seeking consent to take a palliative approach) and the harsh reality (navigating the role in a limiting and siloed environment). CONCLUSION: Paramedics were perceived to have a revered public identity, shaped by their ability to fix a crisis. However, paramedics and other health professionals also expressed fear and vulnerability when taking a palliative approach to care. Paramedics may require consent to move beyond a culture of curative care, yet all participant groups recognised their important adjunct role to support community-based palliative care.

Sexually transmissible infections (STI) and HIV testing and diagnosis among Aboriginal and non-Aboriginal adolescents in contact with the Australian justice system: a cross-sectional study.

BACKGROUND: It is unclear what factors are associated with sexually transmissible infections (STI) and HIV testing and diagnosis among justice-involved adolescents, and if these differ for Aboriginal or Torres Strait Islander peoples. METHODS: A cross-sectional survey of 465 justice-involved adolescents (aged 14-17years) from Australia was conducted between 2016 and 2018. Participants were asked about sexual behaviours, STI/HIV knowledge, and prior STI diagnoses and testing. RESULTS: Approximately 38% (n =130) of those sexually active had ever been screened for STI/HIV and 17.8% (n =23) had been diagnosed with an STI. No participant reported living with HIV. For Aboriginal participants, being male (aOR 3.6, 95% CI 1.3-10.1) and having under three sexual partners in the past 12months (aOR 3.1, 95% CI 1.2-8.0) was associated with never having had an STI/HIV test. For non-Aboriginal participants, being male (aOR 2.7, 95%CI 1.2-5.7), single (aOR 2.4, 95% CI 1.2-4.9), attending school (aOR 2.4, 95% CI 1.1-5.1), not having sought sexual health information (aOR 2.8, 95% CI 1.4-5.8), and having a lower STI/HIV knowledge score (aOR 2.3, 95% CI 1.1-5.0) were associated with never having had an STI/HIV test. Factors associated with STI diagnosis were non-heterosexual sexual orientation (aOR 5.6, 95% CI 1.1-28.2), transactional sex (aOR 11.2, 95% CI 3.0-41.3), and having sought sexual health information (aOR 3.5, 95% CI 1.0-12.5). CONCLUSIONS: Males, particularly Aboriginal male adolescents, should be engaged with sexual health promotion and testing services as soon as they come into contact with the justice system. Approaches should consider different cultural, gender and sexual orientations.

The Role and Value of Chaplains in an Australian Ambulance Service: A Comparative Study of Chaplain and Paramedic Perspectives.

Chaplains are embedded in several ambulance services across Australia, however as Australia's religiosity is currently in decline and questions are being asked about retaining chaplains, little is actually known about their role and value within Ambulance services. The aim of this paper is to present the key findings from interviews with chaplains about their role and value of being ambulance chaplains. These findings are then compared with those of paramedics derived from an earlier phase of this study. Thirteen chaplains participated in semi-structured interviews, and data were analysed using framework analysis. The results indicated that ambulance chaplains provided paramedic-centred emotional and spiritual care through proactively and reactively supporting paramedics in their work. Chaplains saw value in their relational approach which facilitated trust and access, did not seek to 'fix' or diagnose but instead offered physical and emotional presence, and promoted supportive conversations. Chaplains and paramedics valued operationally trained and equipped ambulance chaplains who provided a relational, around the clock, 'frontline' staff support presence in paramedic workplaces, regardless of the paramedic's personal religious/spiritual beliefs.

PET Imaging of Small Extracellular Vesicles via [89Zr]Zr(oxinate)4 Direct Radiolabeling.

Exosomes or small extracellular vesicles (sEVs) are increasingly gaining attention for their potential as drug delivery systems and biomarkers of disease. Therefore, it is important to understand their in vivo biodistribution using imaging techniques that allow tracking over time and at the whole-body level. Positron emission tomography (PET) allows short- and long-term whole-body tracking of radiolabeled compounds in both animals and humans and with excellent quantification properties compared to other nuclear imaging techniques. In this report, we explored the use of [89Zr]Zr(oxinate)4 (a cell and liposome radiotracer) for direct and intraluminal radiolabeling of several types of sEVs, achieving high radiolabeling yields. The radiosynthesis and radiolabeling protocols were optimized for sEV labeling, avoiding sEV damage, as demonstrated using several characterizations (cryoEM, nanoparticle tracking analysis, dot blot, and flow cytometry) and in vitro techniques. Using pancreatic cancer sEVs (PANC1) in a healthy mouse model, we showed that it is possible to track 89Zr-labeled sEVs in vivo using PET imaging for at least up to 24 h. We also report differential biodistribution of intact sEVs compared to intentionally heat-damaged sEVs, with significantly reduced spleen uptake for the latter. Therefore, we conclude that 89Zr-labeled sEVs using this method can reliably be used for in vivo PET tracking and thus allow efficient exploration of their potential as drug delivery systems.

Feasibility and acceptability of an education and training e-resource to support the sexuality, intimacy and relationship needs of older care home residents: a mixed methods study.

BACKGROUND: sexuality, intimacy and relationship needs are often a neglected aspect of the care of older adults in residential care facilities. Improving awareness, knowledge and improving attitudes about these needs among care staff could enhance quality of care and lead to better outcomes for residents. OBJECTIVE: to evaluate the feasibility and acceptability of a co-designed education and training e-resource to help care staff support their residents' sexuality, intimacy and relationship needs. METHODS: we delivered the education and training e-resource to five UK care homes over a 6-month period in a pre-post mixed methods study using surveys, focus groups and individual interviews. RESULTS: fifty-nine members of staff from participating care homes undertook the education and training e-resource. 18/59 (31%) of participants completed all six modules and the pre-post surveys. Eleven participants participated in focus groups/interviews to explore experiences of using the e-resource. The e-resource was successfully implemented in the study homes and found to be acceptable. We found preliminary evidence of positive changes in staff attitudes. Factors that facilitated implementation included support from the care home manager. Barriers identified included IT infrastructure and technology. CONCLUSIONS: the findings provide initial evidence that a co-designed education and training e-resource raised awareness of, and improved attitudes towards, older adults' sexuality and intimacy needs. This work provides the foundation for a next phase to establish the effectiveness of the e-resource on staff practice and resident outcomes.

The Impact of a Novel Operational Readiness Response Model on the Environmental Cleanliness of Emergency Ambulances.

Objectives: Environmental cleanliness of emergency ambulances may be associated with increased risk of healthcare acquired infection (HAI). Surface cleanliness, measured using adenosine triphosphate (ATP) testing, has been demonstrated to correlate with potentially harmful levels of microbial pathogens. In most ambulance services, environmental cleanliness of ambulances and the equipment within them is the responsibility of paramedics. In 2016 NSW Ambulance introduced the Make Ready Model (MRM), in which ambulances are systematically cleaned by non-clinical support staff at the end of each shift. This prospective study aimed to 1) provide a baseline level of ambulance cleanliness; and 2) compare the MRM to a standard cleaning model (SCM). Methods: A prospective comparative study was conducted comparing cleanliness of ambulances in the SCM to those in the MRM. Adenosine-triphosphate (ATP) bioluminescence testing was performed in a pseudo-randomised sample of ambulances. Six 'high touch' areas within each ambulance were systematically sampled. Testing occurred without warning to operational staff. The primary outcome was 'overall bioburden' (OB)' measured in radiant light units ('RLU'). Non-parametric tests were used to assess differences in RLU values between each of the test points, while Poisson multivariate regression was used to compare median overall bioburden between the two groups, adjusting for the confounder variable of 14-day ambulance workload. Results: Sixty-eight ambulances were sampled, 32 from the SCM and 36 from the MRM. Median surface bioburden was significantly lower in the MRM for four of the six test points (preparation table, mobile data terminal, stretcher handles and steering wheel). For the primary outcome of overall bioburden, the unadjusted MRM OB was 35% lower than for the SCM group (RR 0.65 (0.64-0.66; p < 0.01)). After adjusting for the significant confounding variable of 14-day workload, the OB was 38% lower for the MRM group (ARR 0.68 (0.61-0.63; p < 0.001)). Conclusion: The innovative MRM cleaning system was associated with significantly improved cleanliness in frontline emergency ambulances. The magnitude of improvement in cleanliness suggests this cleaning model has the potential to make a major contribution to infection control strategies in paramedicine. Future research should focus on cost effectiveness of the MRM and its applicability to regional and remote ambulance service operations.

Cannabidiol for the Management of Endometriosis and Chronic Pelvic Pain.

OBJECTIVE: To review the available literature on the effect of cannabis-based products on the female reproductive system and establish whether there is any evidence that they benefit or harm patients with endometriosis and, therefore, whether there is sufficient evidence to recommend them. DATA SOURCES: An electronic-based search was performed in PubMed, Embase, and the Cochrane Database. Reference lists of articles retrieved were reviewed, and a gray literature search was also performed. METHODS OF STUDY SELECTION: The original database search yielded 264 articles from PubMed, Embase, and the Cochrane Database, of which 41 were included. One hundred sixty-one studies relating to gynecologic malignancy, conditions unrelated to endometriosis, or therapies unrelated to cannabis-based products were excluded. Twelve articles were included from a gray literature search and review of references. TABULATION, INTEGRATION, AND RESULTS: Most available evidence is from laboratory studies aiming to simulate the effects of cannabis-based products on preclinical endometriosis models. Some show evidence of benefit with cannabis-based products. However, results are conflicting, and the impact in humans cannot necessarily be extrapolated from these data. Few studies exist looking at the effect of cannabis or its derived products in women with endometriosis; the majority are in the form of surveys and are affected by bias. National guidance was also reviewed: at present, this dictates that cannabis-based products can only be prescribed for conditions in which there is clear published evidence of benefit and only when all other treatment options have been exhausted. CONCLUSION: Current treatment options for endometriosis often affect fertility and/or have undesirable side effects that impede long-term management. Cannabis-based products have been suggested as a novel therapeutic option that may circumvent these issues. However, there is a paucity of well-designed, robust studies and randomized controlled trials looking at their use in the treatment of endometriosis. In addition, cannabis use has a potential for harm in the long term, with a possible association with "cannabis use disorder," psychosis, and mood disturbances. At present, national guidance cannot recommend cannabis-based products to patients in the UK owing to lack of clear evidence of benefit. More comprehensive research into the impact of endocannabinoids in the context of endometriosis is required before their use can be recommended or prescribed.