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Background Socio-cultural perceptions surrounding death have profoundly changed since the 1950s with development of modern intensive care and progress in solid organ transplantation. Despite broad support for organ transplantation, many fundamental concepts and practices including brain death, organ donation after circulatory death, and some antemortem interventions to prepare for transplantation continue to be challenged. Attitudes toward the ethical issues surrounding death and organ donation may influence support for and participation in organ donation but differences between and among diverse populations have not been studied. Objectives In order to clarify attitudes toward brain death, organ donation after circulatory death and antemortem interventions in the context of organ donation, we conducted a scoping review of international English-language quantitative surveys in various populations. Study appraisal A search of literature up to October 2020 was performed, using multiple databases. After screening, 45 studies were found to meet pre-specified inclusion criteria. Results 32 studies examined attitudes to brain death, predominantly in healthcare professionals. In most, around 75% of respondents accepted brain death as equivalent to death of the person. Less common perspectives included equating death with irreversible coma and willingness to undertake organ donation even if it caused death. 14 studies examined attitudes to organ donation following circulatory death. Around half of respondents in most studies accepted that death could be confidently diagnosed after only 5 min of cardiorespiratory arrest. The predominant reason was lack of confidence in doctors or diagnostic procedures. Only 6 studies examined attitudes towards antemortem interventions in prospective organ donors. Most respondents supported minimally invasive procedures and only where specific consent was obtained. Conclusions Our review suggests a considerable proportion of people, including healthcare professionals, have doubts about the medical and ethical validity of modern determinations of death. The prognosis of brain injury was a more common concern in the context of organ donation decision-making than certainty of death.

Background In hospital, nurses are often the first to identify patients in cardiorespiratory arrest and must decide whether to call a CODE BLUE and commence cardiopulmonary resuscitation (CPR). In Australia, there are no legal or policy obligations to commence CPR when unequivocal signs of death are present. The use of CPR where it cannot provide any benefit to a patient raises profound questions about decision-making and ethical practice. The aim of this empirical ethics study was to describe hospital-based nurses’ decision-making, perspectives, and experiences of initiating CPR in hospitalised patients who have unequivocal signs of death but lack a Do-Not-Resuscitate (DNR) order. Methods The study was a multisite cross-sectional descriptive survey conducted between October 2023—April 2024. Nurses were presented with two clinical scenarios in which patients were found to have no signs of life: Mr. D, an 84-year-old male with cancer, and Mr. G, a 35-year-old male post-motor vehicle accident. Eligible participants were all nurses working in in-patient units. Descriptive statistics, Pearson Chi-square or Fisher’s exact tests, McNemar test, and binomial logistic regression were used to analyse the data. Results 531 nurses completed the survey. For Mr D, 61.5% ( n  = 324) would call a CODE BLUE, 24.1% ( n  = 127) would perform limited CPR. Only 14.4% ( n  = 76) would confirm death. For Mr G, 93.9% ( n  = 492) would call a CODE BLUE, 4.4% ( n  = 23) would perform limited CPR, and 1.7% ( n  = 9) would confirm death. The major reasons why nurses initiate a CODE BLUE were ‘In the absence of an DNR order, there is no option but to begin CPR’, ‘I am required by hospital policy to do so’, ‘I am required by law to do so’ and ‘It is what I was trained to do’. Conclusions Most nurses would commence CPR in patients with clear signs of death in the absence of a DNR order. This seems most likely related to ignorance or misunderstanding of law, policy and/or the misapplication or professional norms. These results raise important questions about the drivers of nurses understanding of and engagement with CPR. This highlights ethical concerns for care and treatment of patients at the end of their life and underscores the need to examine ethical practice, agency, and professionalism and supports review of policy, practices and education regarding ethical end-of-life decision making and care.

CARDIOGENIC pulmonary edema is a common clinical problem in most hospitals. Despite the use of supplemental oxygen and the administration of drugs to decrease lung water and improve myocardial performance, many patients have severe respiratory failure. Oxygenation may be improved and respiratory-muscle fatigue relieved by intubation and mechanical ventilation 1 ; however, these benefits must be weighed against the potential cardiovascular and respiratory complications. 2 The use of continuous positive airway pressure delivered through a tight-fitting face mask in patients with cardiogenic pulmonary edema was first described more than 50 years ago. 3 The possible benefits of continuous positive airway pressure include an . . .

Objectives. This study aimed to determine which method to triage intensive care patients using chronic comorbidity in a pandemic was perceived to be the fairest by the general public. Secondary objectives were to determine whether the public perceived it fair to provide preferential intensive care triage to vulnerable or disadvantaged people, and frontline healthcare workers. Methods. A postal survey of 2000 registered voters randomly selected from the Australian Electoral Commission electoral roll was performed. The main outcome measures were respondents' fairness rating of four hypothetical intensive care triage methods that assess comorbidity (chronic medical conditions, long-term survival, function and frailty); and respondents' fairness rating of providing preferential triage to vulnerable or disadvantaged people, and frontline healthcare workers. Results. The proportion of respondents who considered it fair to triage based on chronic medical conditions, long-term survival, function and frailty, was 52.1, 56.1, 65.0 and 62.4%, respectively. The proportion of respondents who considered it unfair to triage based on these four comorbidities was 31.9, 30.9, 23.8 and 23.2%, respectively. More respondents considered it unfair to preferentially triage vulnerable or disadvantaged people, than fair (41.8% versus 21.2%). More respondents considered it fair to preferentially triage frontline healthcare workers, than unfair (44.2% versus 30.0%). Conclusion. Respondents in this survey perceived all four hypothetical methods to triage intensive care patients based on comorbidity in a pandemic disaster to be fair. However, the sizable minority who consider this to be unfair indicates that these triage methods could encounter significant opposition if they were to be enacted in health policy.

Noncoding polymorphisms in the fat mass and obesity-associated (FTO) gene represent common alleles that are strongly associated with effects on food intake and adiposity in humans. Previous studies have suggested that the obesity-risk allele rs8050136 in the first intron of FTO alters a regulatory element recognized by the transcription factor CUX1, thereby leading to decreased expression of FTO and retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L). Here, we evaluated the effects of rs8050136 and another potential CUX1 element in rs1421085 on expression of nearby genes in human induced pluripotent stem cell-derived (iPSC-derived) neurons. There were allele-dosage effects on FTO, RPGRIP1L, and AKT-interacting protein (AKTIP) expression, but expression of other vicinal genes, including IRX3, IRX5, and RBL2, which have been implicated in mediating functional effects, was not altered. In vivo manipulation of CUX1, Fto, and/or Rpgrip1l expression in mice affected adiposity in a manner that was consistent with CUX1 influence on adiposity via remote effects on Fto and Rpgrip1l expression. In support of a mechanism, mice hypomorphic for Rpgrip1l exhibited hyperphagic obesity, as the result of diminished leptin sensitivity in Leprb-expressing neurons. Together, the results of this study indicate that the effects of FTO-associated SNPs on energy homeostasis are due in part to the effects of these genetic variations on hypothalamic FTO, RPGRIP1L, and possibly other genes.

Circulating cell-free DNA (ccf-DNA) is becoming an important biomarker for cancer diagnostics and therapy monitoring. The isolation of ccf-DNA from plasma as a \"liquid biopsy\" may begin to replace more invasive tissue biopsies for the detection and analysis of cancer-related mutations. Conventional methods for the isolation of ccf-DNA from plasma are costly, time-consuming, and complex, preventing the use of ccf-DNA biomarkers for point-of-care diagnostics and limiting other biomedical research applications. We used an AC electrokinetic device to rapidly isolate ccf-DNA from 25 μL unprocessed blood. ccf-DNA from 15 chronic lymphocytic leukemia (CLL) patients and 3 healthy individuals was separated into dielectrophoretic (DEP) high-field regions, after which other blood components were removed by a fluidic wash. Concentrated ccf-DNA was detected by fluorescence and eluted for quantification, PCR, and DNA sequencing. The complete process, blood to PCR, required <10 min. ccf-DNA was amplified by PCR with immunoglobulin heavy chain variable region (IGHV)-specific primers to identify the unique IGHV gene expressed by the leukemic B-cell clone, and then sequenced. PCR and DNA sequencing results obtained by DEP from 25 μL CLL blood matched results obtained by use of conventional methods for ccf-DNA isolation from 1 mL plasma and for genomic DNA isolation from CLL patient leukemic B cells isolated from 15-20 mL blood. Rapid isolation of ccf-DNA directly from a drop of blood will advance disease-related biomarker research, accelerate the transition from tissue to liquid biopsies, and enable point-of-care diagnostic systems for patient monitoring.

BackgroundLowe syndrome (LS) is an X linked disease caused by pathogenic variants in the OCRL gene that impacts approximately 1 in 500 000 children. Classic features include congenital cataract, cognitive/behavioural impairment and renal tubulopathy.MethodsThis study is a retrospective review of clinical features reported by family based survey conducted by Lowe Syndrome Association. Frequency of non-ocular clinical feature(s) of LS and their age of onset was summarised. An LS-specific therapy effectiveness scale was used to assess the response to the administered treatment. Expression of OCRL and relevant neuropeptides was measured in postmortem human brain by qPCR. Gene expression in the mouse brain was determined by reanalysis of publicly available bulk and single cell RNA sequencing.ResultsA total of 137 individuals (1 female, 89.1% white, median age 14 years (range 0.8–56)) were included in the study. Short stature (height <3rd percentile) was noted in 81% (n=111) individuals, and 15% (n=20) received growth hormone therapy. Undescended testis was reported in 47% (n=64), and median age of onset of puberty was 15 years. Additional features were dental problems (n=77, 56%), bone fractures (n=63, 46%), hypophosphataemia (n=60, 44%), developmental delay and behavioural issues. OCRL is expressed in human and mouse hypothalami, and in hypothalamic cell clusters expressing Ghrh, Sst, Oxt, Pomc and pituitary cells expressing Gh and Prl.ConclusionsThere is a wide spectrum of the clinical phenotype of LS. Some of the features may be partly driven by the loss of function of OCRL in the hypothalamus and the pituitary.