Norepinephrine Signals Through Astrocytes To Modulate Synapses.

Locus coeruleus (LC)-derived norepinephrine (NE) drives network and behavioral adaptations to environmental saliencies by reconfiguring circuit connectivity, but the underlying synapse-level mechanisms are elusive. Here, we show that NE remodeling of synaptic function is independent from its binding on neuronal receptors. Instead, astrocytic adrenergic receptors and Ca 2+ dynamics fully gate the effect of NE on synapses as the astrocyte-specific deletion of adrenergic receptors and three independent astrocyte-silencing approaches all render synapses insensitive to NE. Additionally, we find that NE suppression of synaptic strength results from an ATP-derived and adenosine A1 receptor-mediated control of presynaptic efficacy. An accompanying study from Chen et al. reveals the existence of an analogous pathway in the larval zebrafish and highlights its importance to behavioral state transitions. Together, these findings fuel a new model wherein astrocytes are a core component of neuromodulatory systems and the circuit effector through which norepinephrine produces network and behavioral adaptations, challenging an 80-year-old status quo.

Chaplaincy and spiritual care in Australian ambulance services: an exploratory cross-sectional study.

Ambulance staff wellbeing programs aim to support the bio-psycho-social and sometimes spiritual needs of paramedics. While evidence demonstrates strong connections between spirituality and/or religion to wellbeing outcomes, little is known about spiritual care in ambulance services or its impact. The aim of this study was to investigate paramedics' perspectives on the role and value of Australian ambulance chaplains. A cross-sectional online study of registered paramedics in Australia was conducted between November and December 2022. Analysis of the 150 responses identified that paramedics viewed the chaplain's role as one built on professional caring relationships that provided proactive and reactive care in paramedic workplaces. Chaplains were perceived to promote wellbeing by incorporating emotional, psychological, social and spiritual care, and assisting paramedics to access additional support. Perceived religiousness of chaplains and organisational factors were barriers to paramedics accessing chaplains, while pre-existing relationships and shared experiences positively influenced paramedics decision to seek chaplain support.

Recommended measurement instruments for menopausal vasomotor symptoms: the COMMA (Core Outcomes in Menopause) consortium.

OBJECTIVE: The aim of the study is to identify suitable definitions and patient-reported outcome measures (PROMs) to assess each of the six core outcomes previously identified through the COMMA (Core Outcomes in Menopause) global consensus process relating to vasomotor symptoms: frequency, severity, distress/bother/interference, impact on sleep, satisfaction with treatment, and side effects. METHODS: A systematic review was conducted to identify relevant definitions for the outcome of side-effects and PROMs with acceptable measurement properties for the remaining five core outcomes. The consensus process, involving 36 participants from 16 countries, was conducted to review definitions and PROMs and make final recommendations for the measurement of each core outcome. RESULTS: A total of 21,207 publications were screened from which 119 reporting on 40 PROMs were identified. Of these 40 PROMs, 36 either did not adequately map onto the core outcomes or lacked sufficient measurement properties. Therefore, only four PROMs corresponding to two of the six core outcomes were considered for recommendation. We recommend the Hot Flash Related Daily Interference Scale to measure the domain of distress, bother, or interference of vasomotor symptoms and to capture impact on sleep (one item in the Hot Flash Related Daily Interference Scale captures interference with sleep). Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events, which is a requirement of Good Clinical Practice. CONCLUSIONS: We identified suitable definitions and PROMs for only three of the six core outcomes. No suitable PROMs were found for the remaining three outcomes (frequency and severity of vasomotor symptoms and satisfaction with treatment). Future studies should develop and validate PROMs for these outcomes.

Perceptions and experiences of paramedics managing people with non-traumatic low back pain: a qualitative study of Australian paramedics.

BACKGROUND: Paramedics are often first providers of care to patients experiencing non-traumatic low back pain (LBP), though their perspectives and experiences with managing these cases remain unclear. OBJECTIVES: This study explored paramedic views of the management of non-traumatic LBP including their role and experience with LBP management, barriers to referral and awareness of ambulance service guidelines. DESIGN: Qualitative study using semistructured interviews conducted between January and April 2023. SETTING: New South Wales Ambulance service. PARTICIPANTS: A purposive sample of 30 paramedics of different specialities employed by New South Wales Ambulance were recruited. RESULTS: Paramedic accounts demonstrated the complexity, challenge, frustration and reward associated with managing non-traumatic LBP. Paramedics perceived that their primary role focused on the assessment of LBP, and that calls to ambulance services were often driven by misconceptions surrounding the management of LBP, and a person's pain severity. Access to health services, patient factors, defensive medicine, paramedic training and education and knowledge of guidelines influenced paramedic management of LBP. CONCLUSION: Paramedics often provide care to non-traumatic LBP cases yet depending on the type of paramedic speciality find these cases to be frustrating, challenging or rewarding to manage due to barriers to referral including access to health services, location, patient factors and uncertainty relating to litigation. Future research should explore patient perspectives towards ambulance service use for the management of their LBP.

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.

Factors Associated with Transgender and Gender Diverse People's Experience of Sexual Coercion, and Help-Seeking and Wellbeing Among Victims/Survivors: Results of the First Australian Trans and Gender Diverse Sexual Health Survey.

Purpose: Our study examined factors associated with transgender and gender diverse ("trans") people's experience of sexual coercion, as well as the factors associated with help-seeking and wellbeing among victims/survivors. Methods: We analyzed cross-sectional data from the first Australian Trans and Gender Diverse Sexual Health Survey, conducted in 2018. Logistic regressions were undertaken to identify factors associated with sexual coercion, help-seeking, and wellbeing. Results: Of the sample of 1448 participants, 53.4% had been sexually coerced, which was associated with older age, Aboriginal or Torres Strait Islander descent, nonbinary gender, being presumed female gender at birth, currently living publicly some or all the time as their affirmed gender, having regular sex, and use of drugs to enhance or alter sexual experiences. Protective factors included having a higher income and access to gender affirming care. Help-seeking was reported among 49.5% of victims/survivors and was associated with having more trans friends. Wellbeing among victims/survivors was associated with being older, residing in regional/remote areas, having higher levels of education and annual income, being presumed female gender at birth, having stronger satisfaction with one's sex life, and good health care access. Wellbeing was not associated with help-seeking. Conclusion: Sexual coercion was prevalent among participants, but help-seeking behavior was low. Protective factors identified underscore the importance of socioeconomic supports, access to health and gender affirming care, and peers. Accessible peer-led and culturally safe preventive and trauma-focused supports should also be considered for trans people who experience sexual coercion.

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.

Cardiomyocyte Alpha-1A Adrenergic Receptors Mitigate Postinfarct Remodeling and Mortality by Constraining Necroptosis.

Clinical studies have shown that α1-adrenergic receptor antagonists (α-blockers) are associated with increased heart failure risk. The mechanism underlying that hazard and whether it arises from direct inhibition of cardiomyocyte α1-ARs or from systemic effects remain unclear. To address these issues, we created a mouse with cardiomyocyte-specific deletion of the α1A-AR subtype and found that it experienced 70% mortality within 7 days of myocardial infarction driven, in part, by excessive activation of necroptosis. We also found that patients taking α-blockers at our center were at increased risk of death after myocardial infarction, providing clinical correlation for our translational animal models.

Menopause: Physiology, definitions, and symptoms.

The menopause transition is usually a gradual process occurring over many years, caused by the cessation of ovarian reproductive function, resulting in the end of menstrual bleeding. In the peri-menopause, ovarian function and therefore the production of the hormones oestrogen, progesterone and testosterone can fluctuate greatly, leading to a wide variety of symptoms, affecting multiple organ systems. Menopause and the management of its associated symptoms can be very challenging for patients and clinicians alike and can negatively impact quality of life. The management options include lifestyle adjustment, talking therapies, dietary supplements as well as prescribed medications, including hormone replacement therapy. The UK's average life expectancy for women is approximately 81 years. Therefore, women will now live up to a third of their life being either peri- or postmenopausal. Thus, understanding and treating, where possible, the symptoms of menopause is essential to reduce the burden associated with this physiological state.

Premenstrual disorders and PMDD - a review.

Defining, diagnosing and managing premenstrual disorders (PMDs) remains a challenge both for general practitioners and specialists. Yet these disorders are common and can have an enormous impact on women. PMDD (premenstrual dysphoric disorder), one severe form of PMD, has a functional impact similar to major depression yet remains under-recognised and poorly treated. The aim of this chapter is to give some clarity to this area, provide a framework for non-specialists to work towards, and to stress the importance of MDT care for severe PMDs, including PMDD.

Clinical practice guidelines in prehospital pain management for paramedics: a systematic review protocol.

OBJECTIVES: The purpose of this review is to examine prehospital pain management clinical practice guidelines (CPGs) to identify recommendations that can be adopted or adapted into paramedic clinical practice. An additional aim is to consider the methodological quality of these CPGs and the recommendations within them. INTRODUCTION: Quality, evidence-based CPGs support clinicians and optimize patient care. However, not all CPGs meet rigorous evidence-based standards, and some may be misleading. As pain is a common reason for patients to access ambulance services, the evaluation of pain management CPGs, their quality, and whether their recommendations can be adopted or adapted into practice is required to increase understanding in this area. INCLUSION CRITERIA: We will include CPGs for pain management intended for prehospital services in civilian communities. CPGs in English published from 2017, and containing clear recommendations addressing pain of any cause will be considered for inclusion. METHODS: This review will combine methodologies, including the PICAR framework (population, intervention, comparison, attributes of eligible CPGs, recommendation characteristics) by Johnston et al. , and the JBI umbrella and scoping review methodologies. The search strategy will cover 12 databases, including PubMed, Embase, and specific CPG databases (eg, GIN Library). Additionally, Google Scholar and Google will be searched, and prehospital organizations without regular publications will be contacted. The AGREE II and AGREE-REX tools will be used to assess the methodological rigor and clinical credibility of the CPGs. The characteristics of both CPGs and the recommendations will be extracted and discussed in the review. REVIEW REGISTRATION: PROSPERO CRD42022352951.

Automatic Extraction of Research Themes in Epidemiological Criminology From PubMed Abstracts From 1946 to 2020: Text Mining Study.

BACKGROUND: The emerging field of epidemiological criminology studies the intersection between public health and justice systems. To increase the value of and reduce waste in research activities in this area, it is important to perform transparent research priority setting considering the needs of research beneficiaries and end users along with a systematic assessment of the existing research activities to address gaps and harness opportunities. OBJECTIVE: In this study, we aimed to examine published research outputs in epidemiological criminology to assess gaps between published outputs and current research priorities identified by prison stakeholders. METHODS: A rule-based method was applied to 23,904 PubMed epidemiological criminology abstracts to extract the study determinants and outcomes (ie, "themes"). These were mapped against the research priorities identified by Australian prison stakeholders to assess the differences from research outputs. The income level of the affiliation country of the first authors was also identified to compare the ranking of research priorities in countries categorized by income levels. RESULTS: On an evaluation set of 100 abstracts, the identification of themes returned an F1-score of 90%, indicating reliable performance. More than 53.3% (11,927/22,361) of the articles had at least 1 extracted theme; the most common was substance use (1533/11,814, 12.97%), followed by HIV (1493/11,814, 12.64%). The infectious disease category (2949/11,814, 24.96%) was the most common research priority category, followed by mental health (2840/11,814, 24.04%) and alcohol and other drug use (2433/11,814, 20.59%). A comparison between the extracted themes and the stakeholder priorities showed an alignment for mental health, infectious diseases, and alcohol and other drug use. Although behavior- and juvenile-related themes were common, they did not feature as prison priorities. Most studies were conducted in high-income countries (10,083/11,814, 85.35%), while countries with the lowest income status focused half of their research on infectious diseases (47/91, 52%). CONCLUSIONS: The identification of research themes from PubMed epidemiological criminology research abstracts is possible through the application of a rule-based text mining method. The frequency of the investigated themes may reflect historical developments concerning disease prevalence, treatment advances, and the social understanding of illness and incarcerated populations. The differences between income status groups are likely to be explained by local health priorities and immediate health risks. Notable gaps between stakeholder research priorities and research outputs concerned themes that were more focused on social factors and systems and may reflect publication bias or self-publication selection, highlighting the need for further research on prison health services and the social determinants of health. Different jurisdictions, countries, and regions should undertake similar systematic and transparent research priority-setting processes.

A microfluidic platform for the controlled synthesis of architecturally complex liquid crystalline nanoparticles.

Soft-matter nanoparticles are of great interest for their applications in biotechnology, therapeutic delivery, and in vivo imaging. Underpinning this is their biocompatibility, potential for selective targeting, attractive pharmacokinetic properties, and amenability to downstream functionalisation. Morphological diversity inherent to soft-matter particles can give rise to enhanced functionality. However, this diversity remains untapped in clinical and industrial settings, and only the simplest of particle architectures [spherical lipid vesicles and lipid/polymer nanoparticles (LNPs)] have been routinely exploited. This is partially due to a lack of appropriate methods for their synthesis. To address this, we have designed a scalable microfluidic hydrodynamic focusing (MHF) technology for the controllable, rapid, and continuous production of lyotropic liquid crystalline (LLC) nanoparticles (both cubosomes and hexosomes), colloidal dispersions of higher-order lipid assemblies with intricate internal structures of 3-D and 2-D symmetry. These particles have been proposed as the next generation of soft-matter nano-carriers, with unique fusogenic and physical properties. Crucially, unlike alternative approaches, our microfluidic method gives control over LLC size, a feature we go on to exploit in a fusogenic study with model cell membranes, where a dependency of fusion on particle diameter is evident. We believe our platform has the potential to serve as a tool for future studies involving non-lamellar soft nanoparticles, and anticipate it allowing for the rapid prototyping of LLC particles of diverse functionality, paving the way toward their eventual wide uptake at an industrial level.

'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.

Rethinking standards on prison cell size in a (post)pandemic world: a scoping review.

OBJECTIVE: To describe the current international, regional and national standards on prison cell spatial density and the evidence for the association between COVID-19 transmission and prison crowding measures to provide recommendations on prison cell spatial density standards for a (post) pandemic world. DESIGN: Scoping review. DATA SOURCES: PubMed, ProQuest, Informit, Criminal Justice Abstracts, Cochrane, Web of Science, Scopus, EMBASE, Google Scholar and Google were searched up to November 2021. ELIGIBILITY CRITERIA: Guidelines were included provided they described standards of prison accommodation with respect to prison cells. Studies were included provided they examined an association between COVID-19 cases and a crowding measure. DATA EXTRACTION AND SYNTHESIS: Data were extracted by one reviewer and cross-checked by another. Quantitative and qualitative data on prison cell standards and characteristics of studies examining an association between COVID-19 and prison crowding were collected.Findings were synthesised qualitatively. RESULTS: Seventeen reports and six studies met eligibility criteria. International and regional standards on cell spatial density were mostly qualitative, with two quantifiable international standards located (3.4 m2 and 3.5 m2 per person for multiple occupancy cells), and two quantifiable regional standards located (4 m2 per person (Europe) and 5.75 m2 or 4 m2 per person (Australia and New Zealand)). Country-based standards varied substantially, ranging from 1.25 m2 per person (Pakistan) to 10 m2 per person (Netherlands). Consideration of airborne transmission of disease in prisons were mostly overlooked or absent to rationalise standards. There was consistent evidence that prison crowding measures were associated with COVID-19 transmission/cases. CONCLUSION: Considering the physics of respiratory emissions, we recommend prison cell spatial density standards be updated to reflect graded levels of risk that consider other factors that combine to inform airborne transmission risk. Decarceration strategies should be considered and become vital if standards are not met.