Understanding practitioner professionalism in Aboriginal and Torres Strait Islander health: lessons from student and registrar placements at an urban Aboriginal and Torres Strait Islander primary health care service

Aboriginal and Torres Strait Islander peoples continue to be pathologised in medical curriculum, leaving graduates feeling unequipped to effectively work cross-culturally. These factors create barriers to culturally safe health care for Aboriginal and Torres Strait Islander peoples. In this pilot pre-post study, we followed the learning experiences of 7 medical students and 4 medical registrars undertaking clinical placements at an urban Aboriginal and Torres Strait Islander primary health care service in 2014. Through analysis and comparison of pre- and post-placement responses to a paper-based case study of a fictitious Aboriginal patient, we identified four learning principles for medical professionalism: student exposure to nuanced, complex and positive representations of Aboriginal peoples; positive practitioner role modelling; interpersonal skills that build trust and minimise patient-practitioner relational power imbalances; and, knowledge, understanding and skills for providing patient centred, holistic care. Though not exhaustive, these principles can increase the capacity of practitioners to foster culturally safe and optimal health care for Aboriginal peoples. Furthermore, competence and effectiveness in Aboriginal health contexts is an essential component of medical professionalism

Synthetic Studies on Gibberellins

Based upon the serendipitous conversion of carbomethoxy-2-(p-methoxyphenyl)-cyclohexane-1-carboxylic acid into endo-2-(p-methoxyphenyl)-cyclohexane-cis-1,5-dicarboxylic acid anhydride, a stereospecific synthesis of 1,2,3,4,4a(betaH),9a(betaH)-hexahydro-7-methoxy-o-oxofluorene-2-carboxylic acid has been achieved in excellent yield, originating from the regiospecific and stereoselective Diels Alder cyclisation between acrylyl chloride and 5-(p-methoxyphenyl)-trans, trans-penta-2,4-dienoyl chloride. The Diels Alder reaction between related dienes and dienophiles was also investigated. A detailed investigation of the intramolecular Dieckmann cyclisation of methyl (1,2,3,4,4a(betaH),9a-hexahydro-2-carbomethoxy-7-methoxy-9-oxofluorenyl-9abeta)-acetate and of its 9-desoxy and 9alpha-hydroxy derivatives as a route to 3-methoxy-6,16-dioxo-9(betaH)-gibb-A-triene suggests that strain factors are the cause of failure of this cyclisation. 3-methoxy-16-oxogibba-1(10),2,4 ,9(11)-tetraene was obtained by acid catalysed cyclisation of the olefinic diazo ketone, 1,2,3,4,4a(betaH)-tetrahydro-Delta9,11-2-diazoacyl-7-methoxyfluorene. A keto-carbenoid C-H insertion reaction applied to the corresponding hexahydro and 9alpha-hydroxy-hexahydro derivatives failed to yield any tetracyclic material. An attempt to extend the Parham hydrofluorene synthesis failed at an early stage when 2-bromo-5-methoxybenzyl alcohol, or its 1-alkoxy-l-ethoxyethane acetal derivative failed to undergo electrophilic halogen exchange. A similar lack of success was experienced with the corresponding Grignard reagent

Nicotine-Induced Effects on Nicotinic Acetylcholine Receptors (nAChRs), Ca2+ and Brain-Derived Neurotrophic Factor (BDNF) in STC-1 Cells

In addition to the T2R bitter taste receptors, neuronal nicotinic acetylcholine receptors (nAChRs) have recently been shown to be involved in the bitter taste transduction of nicotine, acetylcholine and ethanol. However, at present it is not clear if nAChRs are expressed in enteroendocrine cells other than beta cells of the pancreas and enterochromaffin cells, and if they play a role in the synthesis and release of neurohumoral peptides. Accordingly, we investigated the expression and functional role of nAChRs in enteroendocrine STC-1 cells. Our studies using RT-PCR, qRT-PCR, immunohistochemical and Western blotting techniques demonstrate that STC-1 cells express several α and β nAChR subunits. Exposing STC-1 cells to nicotine acutely (24h) or chronically (4 days) induced a differential increase in the expression of nAChR subunit mRNA and protein in a dose- and time-dependent fashion. Mecamylamine, a non-selective antagonist of nAChRs, inhibited the nicotineinduced increase in mRNA expression of nAChRs. Exposing STC-1 cells to nicotine increased intracellular Ca2+ in a dose-dependent manner that was inhibited in the presence of mecamylamine or dihydro-β-erythroidine, a α4β2 nAChR antagonist. Brain-derived neurotrophic factor (BDNF) mRNA and protein were detected in STC-1 cells using RT-PCR, specific BDNF antibody, and enzyme-linked immunosorbent assay. Acute nicotine exposure (30 min) decreased the cellular content of BDNF in STC-1 cells. The nicotine-induced decrease in BDNF was inhibited in the presence of mecamylamine. We also detected α3 and β4 mRNA in intestinal mucosal cells and α3 protein expression in intestinal enteroendocrine cells. We conclude that STC-1 cells and intestinal enteroendocrine cells express nAChRs. In STC-1 cells nAChR expression is modulated by exposure to nicotine in a doseand time-dependent manner. Nicotine interacts with nAChRs and inhibits BDNF expression in STC-1 cells

Malignancy and all-cause mortality; incidence in adolescents and young adults living with perinatally acquired HIV.

Background: Adults living with HIV have an increased risk of malignancy yet there is a paucity of data for adolescents and young adults (AYA) with perinatally acquired HIV (PaHIV). Methods: Retrospective cohort analysis of all-cause mortality and malignancies in AYA with PaHIV aged 10-24 years attending a tertiary unit from 01 January 2004 to 31 December 2017, assessing cancer presentation, immunology and comparing mortality and malignancy incidence to age-matched UK general population rates. Results: A total of 290 AYA with PaHIV contributed 2644 person-years of follow up. Six (2.0%) died within the study period at a median age of 17 years (interquartile range [IQR]15-19), 3 of malignancy, 2 with end-stage HIV and 1 with cryptococcal meningitis. Overall mortality rate was 2.3/1000 person-years, with an age-matched general population rate of 0.2/1000 person-years. Eight (2.8%) were diagnosed with a malignancy; 6 with lymphoma (n=3 Hodgkin's, n=1 Burkitt's, n=2 B-cell) and one each with hepatocellular carcinoma and gastrointestinal adenocarcinoma. At cancer diagnosis the median age was 19 years (IQR 14-23), median CD4 T cell count was 453 cells/mm3 (IQR 231-645) and median length of HIV viremia was 15 years (IQR 12-17). The incidence rate of a malignancy was 3.0/1000 person-years in AYA with PaHIV, whilst that in the age-matched general population is 0.2/1000 person-years. Conclusion: AYA living with PaHIV had an increased risk of all-cause mortality and of malignancy compared to their uninfected peers, with the excess in malignancy driven by lymphomas. It is hoped that earlier access to antiretroviral therapy will mitigate some of the AIDS-defining and non-AIDS defining risks for future generations

Congenital Cytomegalovirus and Autoimmune Neutropenia: Cause or Coincidence?

BACKGROUND: Congenital cytomegalovirus (CCMV) accounts for high rates of infant morbidity and mortality. Neutropenia is a common finding in CCMV infection, of which the age of presentation overlaps with autoimmune neutropenia (AIN). AIN represents one of the most common forms of chronic neutropenia in childhood. METHODS: A literature search exploring biological associations between CCMV and AIN was conducted: PubMed (MEDLINE), Ovid and Web of Science. We further describe 2 cases of concurrent CCMV and AIN. Both cases were confirmed with the indirect granulocyte immunofluorescence test and alternative etiologies for neutropenia excluded. RESULTS: Our 2 patients represent confirmed cases of AIN in infants with CCMV. One patient demonstrated neutropenia while undergoing treatment with Valganciclovir, while the other was never treated. With interruption of Valganciclovir in infant A, neutrophil counts (ANC) did not improve and upon resumption of treatment ANC remained static. CONCLUSIONS: Further studies examining a possible biologic link between CCMV and AIN are advocated for. We encourage clinicians to actively consider AIN in the differential diagnosis of all infants with CCMV presenting with neutropenia

Flows of Knowledge, Expertise and Influence:A Method for Assessing Policy and Practice Impacts from Social Science Research

Social science research undoubtedly does impact on public policy and practice but Such non-academic impacts are rarely amenable to precise, quantitative metrics. In the of accountability, it is however possible to find proxy indicators of connectivity with research users and these may form steps toward impacts. Understanding these connections can lead to a deeper appreciation of the factors that shape the processes leading to research uptake. This study adopted a detailed and largely qualitative approach to identify the flows of knowledge, expertise and influence that take place during the process of knowledge transfer in order to trial a method for assessing policy and practice impacts from social science research. As a corollary to this assessment, the Study further identified five factors that can influence and enhance the process of knowledge exchange between researchers and users.</p

Cyclic-AMP regulates postnatal development of neural and behavioral responses to NaCl in rats

During postnatal development rats demonstrate an age-dependent increase in NaCl chorda tympani (CT) responses and the number of functional apical amiloride-sensitive epithelial Na+channels (ENaCs) in salt sensing fungiform (FF) taste receptor cells (TRCs). Currently, the intracellular signals that regulate the postnatal development of salt taste have not been identified. We investigated the effect of cAMP, a downstream signal for arginine vasopressin (AVP) action, on the postnatal development of NaCl responses in 19–23 day old rats. ENaC-dependent NaCl CT responses were monitored after lingual application of 8-chlorophenylthio-cAMP (8-CPT-cAMP) under open-circuit conditions and under ±60 mV lingual voltage clamp. Behavioral responses were tested using 2 bottle/24h NaCl preference tests. The effect of [deamino-Cys1, D-Arg8]-vasopressin (dDAVP, a specific V2R agonist) was investigated on ENaC subunit trafficking in rat FF TRCs and on cAMP generation in cultured adult human FF taste cells (HBO cells). Our results show that in 19–23 day old rats, the ENaC-dependent maximum NaCl CT response was a saturating sigmoidal function of 8-CPT-cAMP concentration. 8-CPT-cAMP increased the voltage-sensitivity of the NaCl CT response and the apical Na+ response conductance. Intravenous injections of dDAVP increased ENaC expression and γ-ENaC trafficking from cytosolic compartment to the apical compartment in rat FF TRCs. In HBO cells dDAVP increased intracellular cAMP and cAMP increased trafficking of γ- and δ-ENaC from cytosolic compartment to the apical compartment 10 min post-cAMP treatment. Control 19–23 day old rats were indifferent to NaCl, but showed clear preference for appetitive NaCl concentrations after 8-CPT-cAMP treatment. Relative to adult rats, 14 day old rats demonstrated significantly less V2R antibody binding in circumvallate TRCs. We conclude that an age-dependent increase in V2R expression produces an AVP-induced incremental increase in cAMP that modulates the postnatal increase in TRC ENaC and the neural and behavioral responses to NaCl

Clinical Mortality in a Large COVID-19 Cohort: Observational Study.

BACKGROUND: Northwell Health, an integrated health system in New York, has treated more than 15,000 inpatients with COVID-19 at the US epicenter of the SARS-CoV-2 pandemic. OBJECTIVE: We describe the demographic characteristics of patients who died of COVID-19, observation of frequent rapid response team/cardiac arrest (RRT/CA) calls for non-intensive care unit (ICU) patients, and factors that contributed to RRT/CA calls. METHODS: A team of registered nurses reviewed the medical records of inpatients who tested positive for SARS-CoV-2 via polymerase chain reaction before or on admission and who died between March 13 (first Northwell Health inpatient expiration) and April 30, 2020, at 15 Northwell Health hospitals. The findings for these patients were abstracted into a database and statistically analyzed. RESULTS: Of 2634 patients who died of COVID-19, 1478 (56.1%) had oxygen saturation levels ≥90% on presentation and required no respiratory support. At least one RRT/CA was called on 1112/2634 patients (42.2%) at a non-ICU level of care. Before the RRT/CA call, the most recent oxygen saturation levels for 852/1112 (76.6%) of these non-ICU patients were at least 90%. At the time the RRT/CA was called, 479/1112 patients (43.1%) had an oxygen saturation of \u3c80%. CONCLUSIONS: This study represents one of the largest reviewed cohorts of mortality that also captures data in nonstructured fields. Approximately 50% of deaths occurred at a non-ICU level of care despite admission to the appropriate care setting with normal staffing. The data imply a sudden, unexpected deterioration in respiratory status requiring RRT/CA in a large number of non-ICU patients. Patients admitted at a non-ICU level of care suffered rapid clinical deterioration, often with a sudden decrease in oxygen saturation. These patients could benefit from additional monitoring (eg, continuous central oxygenation saturation), although this approach warrants further study

Perception of the Importance of Traditional Country Foods to the Physical, Mental, and Spiritual Health of Labrador Inuit

Country foods play an integral role in Inuit life by providing nutrition and a spiritual connection to the land. However, they can harbour foodborne pathogens, such as zoonotic parasites or bacteria, which can cause disease in humans who consume contaminated meat that has been inadequately cooked. Given the heavy reliance of Inuit on subsistence living, it is important to have a clear understanding of the relative safety of these foods and the role that they play in a changing Inuit society. This community-based participatory research project involved Inuit residents of Nain, Nunatsiavut, Canada. Data on Inuit perceptions of the role, importance, and safety of country foods were collected during a series of interviews with focus groups and key informants. Despite the extremely positive views they expressed about country foods and the connections they provide to the land, community, and past, participants had major concerns about human expansion in the North, mining operations, chemical contamination, and the impact of these issues on animals and the food harvested from those animals. Also of concern was a perceived decrease in the importance of country food in their community in general, and specifically among children. These findings provide an understanding of Nunatsiavut residents’ perceptions that is essential to planning effective, culturally appropriate dissemination of public health messages about the safe consumption of country foods.La nourriture de campagne revêt une grande importance dans la vie des Inuits car elle présente à la fois une source de nutrition de même qu’un attachement spirituel à la terre. Cependant, cette nourriture peut être assortie de pathogènes d’origine alimentaire prenant notamment la forme de parasites ou de bactéries zoonotiques qui peuvent entraîner des maladies chez l’être humain qui consomme de la viande contaminée dont la cuisson n’est pas adéquate. Étant donné la grande dépendance des Inuits par rapport à l’alimentation de subsistance, il est important de bien comprendre la salubrité relative de ces aliments et du rôle qu’ils jouent au sein de la société inuite en pleine évolution. Ce projet de recherche communautaire a fait appel à des habitants inuits de Nain, Nunatsiavut, au Canada. Des données relatives aux perceptions des Inuits sur le rôle, l’importance et la salubrité de la nourriture de campagne ont été recueillies dans le cadre d’une série d’entrevues réalisées auprès de groupes de discussion et d’intervenants-clés. Malgré les points de vue extrêmement positifs exprimés au sujet de la nourriture de campagne et de l’attachement qu’elle procure à la terre, à la collectivité et au passé, les participants ont exprimé de grandes préoccupations à propos de l’expansion humaine dans le Nord, de l’exploitation minière, de la contamination chimique et de l’incidence de ces enjeux sur les animaux et les sources de nourriture provenant de ces animaux. Par ailleurs, ils s’inquiétaient de la diminution perçue de l’importance de la nourriture de campagne au sein de leur communauté en général, plus précisément chez les enfants. Ces constatations permettent de comprendre les perceptions des habitants de Nunatsiavut, ce qui est essentiel à une planification efficace et à la dissémination culturellement appropriée des messages de santé publique au sujet de la consommation sécuritaire de la nourriture de campagne

Association between polygenic risk for Alzheimer’s disease, brain structure and cognitive abilities in UK Biobank

Previous studies testing associations between polygenic risk for late-onset Alzheimer’s disease (LOAD-PGR) and brain magnetic resonance imaging (MRI) measures have been limited by small samples and inconsistent consideration of potential confounders. This study investigates whether higher LOAD-PGR is associated with differences in structural brain imaging and cognitive values in a relatively large sample of non-demented, generally healthy adults (UK Biobank). Summary statistics were used to create PGR scores for n = 32,790 participants using LDpred. Outcomes included 12 structural MRI volumes and 6 concurrent cognitive measures. Models were adjusted for age, sex, body mass index, genotyping chip, 8 genetic principal components, lifetime smoking, apolipoprotein (APOE) e4 genotype and socioeconomic deprivation. We tested for statistical interactions between APOE e4 allele dose and LOAD-PGR vs. all outcomes. In fully adjusted models, LOAD-PGR was associated with worse fluid intelligence (standardised beta [β] = −0.080 per LOAD-PGR standard deviation, p = 0.002), matrix completion (β = −0.102, p = 0.003), smaller left hippocampal total (β = −0.118, p = 0.002) and body (β = −0.069, p = 0.002) volumes, but not other hippocampal subdivisions. There were no significant APOE x LOAD-PGR score interactions for any outcomes in fully adjusted models. This is the largest study to date investigating LOAD-PGR and non-demented structural brain MRI and cognition phenotypes. LOAD-PGR was associated with smaller hippocampal volumes and aspects of cognitive ability in healthy adults and could supplement APOE status in risk stratification of cognitive impairment/LOAD