Legal provisions on medical aid in dying encode moral intuition.

In recent decades, many jurisdictions have moved toward legalizing euthanasia and assisted suicide, alongside a near-universal increase in public acceptance of medical aid in dying. Here, we draw on a comprehensive quantitative review of current laws on assisted dying, experimental survey evidence, and four decades of time-series data to explore the relationship between these legislative transitions and change in moral attitudes. Our analyses reveal that existing laws on medical aid in dying impose a common set of eligibility restrictions, based on the patient's age, decision-making capacity, prognosis, and the nature of their illness. Fulfillment of these eligibility criteria elevates public moral approval of physician-assisted death, equally in countries with (i.e., Spain) and without (i.e., the United Kingdom) assisted dying laws. Finally, historical records of public attitudes toward euthanasia across numerous countries uncovered anticipatory growth in moral approval leading up to legalization, but no accelerated growth thereafter. Taken together, our findings suggest that the enactment of medical aid in dying laws, and their specific provisions, crystallize patterns in moral intuition.

Mapping trust relationships in organ donation and transplantation: a conceptual model.

The organ donation and transplantation (ODT) system heavily relies on the willingness of individuals to donate their organs. While it is widely believed that public trust plays a crucial role in shaping donation rates, the empirical support for this assumption remains limited. In order to bridge this knowledge gap, this article takes a foundational approach by elucidating the concept of trust within the context of ODT. By examining the stakeholders involved, identifying influential factors, and mapping the intricate trust relationships among trustors, trustees, and objects of trust, we aim to provide a comprehensive understanding of trust dynamics in ODT. We employ maps and graphs to illustrate the functioning of these trust relationships, enabling a visual representation of the complex interactions within the ODT system. Through this conceptual groundwork, we pave the way for future empirical research to investigate the link between trust and organ donation rates, informed by a clarified understanding of trust in ODT. This study can also provide valuable insights to inform interventions and policies aimed at enhancing organ donation rates.

Public Preferences for Digital Health Data Sharing: Discrete Choice Experiment Study in 12 European Countries.

BACKGROUND: With new technologies, health data can be collected in a variety of different clinical, research, and public health contexts, and then can be used for a range of new purposes. Establishing the public's views about digital health data sharing is essential for policy makers to develop effective harmonization initiatives for digital health data governance at the European level. OBJECTIVE: This study investigated public preferences for digital health data sharing. METHODS: A discrete choice experiment survey was administered to a sample of European residents in 12 European countries (Austria, Denmark, France, Germany, Iceland, Ireland, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom) from August 2020 to August 2021. Respondents answered whether hypothetical situations of data sharing were acceptable for them. Each hypothetical scenario was defined by 5 attributes ("data collector," "data user," "reason for data use," "information on data sharing and consent," and "availability of review process"), which had 3 to 4 attribute levels each. A latent class model was run across the whole data set and separately for different European regions (Northern, Central, and Southern Europe). Attribute relative importance was calculated for each latent class's pooled and regional data sets. RESULTS: A total of 5015 completed surveys were analyzed. In general, the most important attribute for respondents was the availability of information and consent during health data sharing. In the latent class model, 4 classes of preference patterns were identified. While respondents in 2 classes strongly expressed their preferences for data sharing with opposing positions, respondents in the other 2 classes preferred not to share their data, but attribute levels of the situation could have had an impact on their preferences. Respondents generally found the following to be the most acceptable: a national authority or academic research project as the data user; being informed and asked to consent; and a review process for data transfer and use, or transfer only. On the other hand, collection of their data by a technological company and data use for commercial communication were the least acceptable. There was preference heterogeneity across Europe and within European regions. CONCLUSIONS: This study showed the importance of transparency in data use and oversight of health-related data sharing for European respondents. Regional and intraregional preference heterogeneity for "data collector," "data user," "reason," "type of consent," and "review" calls for governance solutions that would grant data subjects the ability to control their digital health data being shared within different contexts. These results suggest that the use of data without consent will demand weighty and exceptional reasons. An interactive and dynamic informed consent model combined with oversight mechanisms may be a solution for policy initiatives aiming to harmonize health data use across Europe.

Cigarette Smoke Directly Promotes Pulmonary Arterial Remodeling and Kv7.4 Channel Dysfunction.

Rationale: Cigarette smoke is considered the chief leading cause of chronic obstructive pulmonary disease (COPD). Its impact on the progressive deterioration of airways has been extensively studied, but its direct effects on the pulmonary vasculature are less known. Objectives: To prove that pulmonary arterial remodeling in patients with COPD is not just a consequence of alveolar hypoxia but also due to the direct effects of cigarette smoke on the pulmonary vascular bed. Methods: We have used different molecular and cell biology approaches, as well as traction force microscopy, wire myography, and patch-clamp techniques in human cells and freshly isolated pulmonary arteries. In addition, we relied on in vivo models and human samples to analyze the effects of cigarette smoke on pulmonary vascular tone alterations. Measurements and Main Results: Cigarette smoke extract exposure directly promoted a hypertrophic, senescent phenotype that in turn contributed, through the secretion of inflammatory molecules, to an increase in the proliferative potential of nonexposed cells. Interestingly, these effects were significantly reversed by antioxidants. Furthermore, cigarette smoke extract affected cell contractility and dysregulated the expression and activity of the voltage-gated K+ channel Kv7.4. This contributed to the impairment of vasoconstriction and vasodilation responses. Most importantly, the levels of this channel were diminished in the lungs of smoke-exposed mice, smokers, and patients with COPD. Conclusions: Cigarette smoke directly contributes to pulmonary arterial remodeling through increased cell senescence, as well as vascular tone alterations because of diminished levels and function in the Kv7.4 channel. Strategies targeting these pathways may lead to novel therapies for COPD.

Attitudes of European students towards family decision-making and the harmonisation of consent systems in deceased organ donation: a cross-national survey.

BACKGROUND: European countries are increasingly harmonising their organ donation and transplantation policies. Although a growing number of nations are moving to presumed consent to deceased organ donation, no attempts have been made to harmonise policies on individual consent and the role of the family in the decision-making process. Little is known about public awareness of and attitudes towards the role of the family in their own country and European harmonisation on these health policy dimensions. To improve understanding of these issues, we examined what university students think about the role of the family in decision-making in deceased organ donation and about harmonising consent policies within Europe. METHODS: Using LimeSurvey© software, we conducted a comparative cross-sectional international survey of 2193 university students of health sciences and humanities/social sciences from Austria (339), Belgium (439), Denmark (230), Germany (424), Greece (159), Romania (190), Slovenia (190), and Spain (222). RESULTS: Participants from opt-in countries may have a better awareness of the family's legal role than those from opt-out countries. Most respondents opposed the family veto, but they were more ambivalent towards the role of the family as a surrogate decision-maker. The majority of participants were satisfied with the family's legal role. However, those who were unsatisfied preferred to limit family involvement. Overall, participants were opposed to the idea of national sovereignty over consent policies. They favoured an opt-out policy harmonisation and were divided over opt-in. Their views on harmonisation of family involvement were consistent with their personal preferences. CONCLUSIONS: There is overall division on whether families should have a surrogate role, and substantial opposition to granting them sole authority over decision-making. If European countries were to harmonise their policies on consent for organ donation, an opt-out system that grants families a surrogate decision-making role may enjoy the widest public support.

[Deliberative dialogue with Ibero-American universities on interventions in student mental health during the COVID-19 pandemicDiálogo deliberativo com universidades ibero-americanas sobre intervenções em saúde mental dos estudantes na pandemia de COVID-19]. / Diálogo deliberativo con universidades iberoamericanas sobre intervenciones en salud mental estudiantil durante la pandemia de COVID-19.

Objective: To contextualize a synthesis of evidence on interventions in student mental health during the COVID-19 pandemic through a deliberative dialogue with Ibero-American universities. Methods: An evidence synthesis and synchronous dialogues were previously conducted, consisting of subgroup discussions about the design and implementation of mental health interventions. An analysis of dialogic data was conducted, then organized by topic. Results: Fifty-seven representatives of 17 public and private Ibero-American universities participated in the meeting. In terms of the design of interventions, mental health is perceived as neglected, although its profile was raised by the pandemic. Interventions are guided by detection of needs; scientific evidence is rarely used to design them. Importance was given to forming an interdisciplinary team with continuous training in order to design a specific program that also covers families and teaching/administrative staff. In terms of implementation, problems include saturation of services due to high demand and lack of basic resources among students. Regarding the provision of resources, the influence of the broader context, including the institutional context, is undeniable. The dialogues were perceived as an opportunity to build a new set of interventions. Conclusions: These dialogues enriched the description of interventions already described in the literature on student mental health during the COVID-19 pandemic. However, implementing such interventions in the region means addressing previous neglect and a high level of unmet basic needs.

Objetivo: Contextualizar uma síntese de evidências sobre intervenções em saúde mental de estudantes universitários na pandemia de COVID-19, por meio do diálogo deliberativo com universidades ibero-americanas. Métodos: A partir de uma síntese de evidências previamente elaborada, o diálogo síncrono foi conduzido por meio de discussões em subgrupos sobre o planejamento e a implementação de intervenções em saúde mental. Os dados obtidos foram analisados e resumidos por área temática. Resultados: Cinquenta e sete integrantes de 17 universidades ibero-americanas públicas e privadas participaram do encontro. Os participantes indicaram que a saúde mental é negligenciada no planejamento das intervenções, mas ganhou visibilidade na pandemia. As intervenções são direcionadas às necessidades identificadas e raramente planejadas com base em evidências científicas. Disseram considerar importante formar uma equipe interdisciplinar com capacitação contínua para planejar um programa específico que englobe também familiares e o corpo docente e administrativo. Implementar intervenções é complicado porque os serviços estão sobrecarregados devido à grande demanda e à falta de recursos básicos para os estudantes. O contexto macro e institucional claramente influencia a disponibilização de recursos. O diálogo foi visto como uma oportunidade para consolidar um novo conjunto de intervenções. Conclusões: O presente diálogo contribuiu para enriquecer a literatura de intervenções de saúde mental para estudantes universitários na pandemia de COVID-19. Implementar intervenções no nosso contexto requer sanar as falhas por negligência passada e as enormes necessidades básicas não atendidas.

How do people use 'killing', 'letting die' and related bioethical concepts? Contrasting descriptive and normative hypotheses.

Bioethicists involved in end-of-life debates routinely distinguish between 'killing' and 'letting die'. Meanwhile, previous work in cognitive science has revealed that when people characterize behaviour as either actively 'doing' or passively 'allowing', they do so not purely on descriptive grounds, but also as a function of the behaviour's perceived morality. In the present report, we extend this line of research by examining how medical students and professionals (N = 184) and laypeople (N = 122) describe physicians' behaviour in end-of-life scenarios. We show that the distinction between 'ending' a patient's life and 'allowing' it to end arises from morally motivated causal selection. That is, when a patient wishes to die, her illness is treated as the cause of death and the doctor is seen as merely allowing her life to end. In contrast, when a patient does not wish to die, the doctor's behaviour is treated as the cause of death and, consequently, the doctor is described as ending the patient's life. This effect emerged regardless of whether the doctor's behaviour was omissive (as in withholding treatment) or commissive (as in applying a lethal injection). In other words, patient consent shapes causal selection in end-of-life situations, and in turn determines whether physicians are seen as 'killing' patients, or merely as 'enabling' their death.

Lauren subtypes of advanced gastric cancer influence survival and response to chemotherapy: real-world data from the AGAMENON National Cancer Registry.

BACKGROUND: The choice of chemotherapy in HER2-negative gastric cancer is based on centre's preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS). METHODS: We have conducted a multicenter study in 31 hospitals. The eligibility criteria include diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2 negativity, and chemotherapy containing 2-3 drugs. Cox proportional hazards regression adjusted for confounding factors, with tests of 'treatment-by-histology' interaction, was used to estimate treatment effect. RESULTS: Our registry contains 1303 tumours analysable for OS end points and 730 evaluable for overall response rate (ORR). A decrease in ORR was detected in the presence of a diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525-0.987), P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in the intestinal type. The diffuse type displayed increased mortality with hazard ratio (HR) of 1.201 (95% CI, 1.054-1.368), P=0.0056. Patients receiving chemotherapy with docetaxel exhibited increased OS limited to the intestinal type: HR 0.65 (95% CI, 0.49-0.87), P=0.024, with no increment in OS for the subset having a diffuse component. With respect to progression-free survival (PFS), a significant interaction was seen in the effect of docetaxel-containing schedules, with better PFS limited to the intestinal type subgroup, in the comparison against any other schedule: HR 0.65 (95% CI, 0.50-0.85), P=0.015, and against anthracycline-based regimens: HR 0.64 (95% CI, 0.46-0.88), P=0.046. CONCLUSIONS: As a conclusion, in this registry, Lauren classification tumour subtypes predicted survival and responded differently to chemotherapy. Future clinical trials should stratify effect estimations based on histology.

Determination of Death: A Discussion on Responsible Scholarship, Clinical Practices, and Public Engagement.

The concept and determination of death by neurological or cardio-circulatory criteria play a crucial role for medical practice, society, and the law. Academic debates on death determination have regained momentum, and recent cases involving the neurological determination of death ("brain death") in the United States have sparked sustained public debate. The determination of death by neurological criterion (irreversible cessation of the whole brain or of the brain stem) is medically practiced in at least 80 countries. However, academic debates persist about the conceptual and scientific validity of death determined by neurological criterion. The cardio-circulatory criterion, which permits organ donation following cardio-circulatory arrest, has also recently been challenged. Given the presence of academic debates, several questions ensue about the responsible conduct of clinicians and scholars involved in clinical practices and academic research. This article identifies tension points for responsible practices in the domains of scholarship, clinical practice, and public discourse and formulates suggestions to stimulate further dialogue on responsible practices and to identify questions in need of further research.

Dying and multiplying life.

It was only after James P. Lovette's death, in 2006, that I discovered that the twenty-four-year-old colleague and friend with whom I had spent so many afternoons debating issues in organ transplantation had been the first successful child heart transplantee in the world and one of the longest-living survivors of a second transplant. During the years we met, he never even hinted at the fact that three different hearts had beaten in his chest. The revelation that his life had been an almost uninterrupted chain of medical challenges suddenly made me appreciate his quirkiness in a whole new light. Organ transplantation crudely exemplifies a traditional moral dilemma between means and ends: in order to save a life, someone else has to die. Bioethicists involved in this field have the role of identifying the ethical issues surrounding organ donation and helping others to argue in an intelligible and convincing way. In my view, bioethicists have the obligation to foster a discussion as open and transparent as possible on these matters. Still, I sometimes fear that I may be helping to cause unnecessary harms to potential recipients who are desperately waiting for a vital organ. Scholars would be chillingly cold if their quest for truth systematically came at the cost of lives lost. Every life can be meaningful and provide meaning to many others. This is true even with organ recipients, who often have short lives full of considerable suffering.

Systematic review of the utility and limits of 3D printing in spine surgery.

OBJECTIVE: The main objective of this study has been to demonstrate why additive printing allows to make complex surgical pathological processes that affect the spine more visible and understandable, increasing precision, safety and reliability of the surgical procedure. METHODS: A systematic review of the articles published in the last 10 years on 3D printing-assisted spinal surgery was carried out, in accordance with PRISMA 2020 declaration. Keywords "3D printing" and "spine surgery" were searched in Pubmed, Embase, Cochrane Database of Systematic Reviews, Google Scholar and Opengrey databases, which was completed with a manual search through the list of bibliographic references of the articles that were selected following the defined inclusion and exclusion criteria. RESULTS: From the analysis of the 38 selected studies, it results that 3D printing is useful in surgical planning, medical teaching, doctor-patient relationship, design of navigation templates and spinal implants, and research, optimizing the surgical process by focusing on the patient, offering magnificent support during the surgical procedure. CONCLUSIONS: The use of three-dimensional printing biomodels allows: making complex surgical pathological processes that affect the spine more visible and understandable; increase the accuracy, precision and safety of the surgical procedure, and open up the possibility of implementing personalized treatments, mainly in tumor surgery.

Biodegradation of Nitrile Gloves as Sole Carbon Source of Pseudomonas aeruginosa in Liquid Culture.

Nitrile gloves have become a significant environmental pollutant after the COVID-19 pandemic due to their single-use design. This study examines the capability of P. aeruginosa to use nitrile gloves as its sole carbon energy source. Biodegradation was determined by P. aeruginosa adapting to increasing nitrile glove concentrations at 1%, 3%, and 5% (w/v). The growth kinetics of P. aeruginosa were evaluated, as well as the polymer weight loss. Topographic changes on the glove surfaces were examined using SEM, and FT-IR was used to evaluate the biodegradation products of the nitrile gloves. Following the establishment of a biofilm on the glove surface, the nitrile toxicity was minimized via biodegradation. The result of the average weight loss of nitrile gloves was 2.25%. FT-IR analysis revealed the presence of aldehydes and aliphatic amines associated with biodegradation. SEM showed P. aeruginosa immersed in the EPS matrix, causing the formation of cracks, scales, protrusions, and the presence of semi-spherical particles. We conclude that P. aeruginosa has the capability to use nitrile gloves as its sole carbon source, even up to 5%, through biofilm formation, demonstrating the potential of P. aeruginosa for the degradation of nitrile gloves.

Recent United States Developments in the Pharmacological Treatment of Dry Eye Disease.

Dry eye disease (DED) can arise from a variety of factors, including inflammation, meibomian gland dysfunction (MGD), and neurosensory abnormalities. Individuals with DED may exhibit a range of clinical signs, including tear instability, reduced tear production, and epithelial disruption, that are driven by different pathophysiological contributors. Those affected often report a spectrum of pain and visual symptoms that can impact physical and mental aspects of health, placing an overall burden on an individual's well-being. This cumulative impact of DED on an individual's activities and on society underscores the importance of finding diverse and effective management strategies. Such management strategies necessitate an understanding of the underlying pathophysiological mechanisms that contribute to DED in the individual patient. Presently, the majority of approved therapies for DED address T cell-mediated inflammation, with their tolerability and effectiveness varying across different studies. However, there is an emergence of treatments that target additional aspects of the disease, including novel inflammatory pathways, abnormalities of the eyelid margin, and neuronal function. These developments may allow for a more nuanced and precise management strategy for DED. This review highlights the recent pharmacological advancements in DED therapy in the United States. It discusses the mechanisms of action of these new treatments, presents key findings from clinical trials, discusses their current stage of development, and explores their potential applicability to different sub-types of DED. By providing a comprehensive overview of products in development, this review aims to contribute valuable insights to the ongoing efforts in enhancing the therapeutic options available to individuals suffering from DED.

The Role of Astrocytes and Alpha-Synuclein in Parkinson's Disease: A Review.

The search for new therapies to reduce symptoms and find a cure for Parkinson's disease has focused attention on two key points: the accumulation of alpha-synuclein aggregates and astrocytes. The former is a hallmark of the disease, while the latter corresponds to a type of glial cell with an important role in both the prevention and development of this neurodegenerative disorder. Traditionally, research has focused on therapies targeting dopaminergic neurons. Currently, as more is known about the genetic and molecular factors and the neuroglial interaction in the disease, great emphasis has been placed on the neuroprotective role of astrocytes in the early stages of the disease and on the astrocytic capture of alpha-synuclein under both physiological and pathological conditions. This review aims to analyze the contribution of alpha-synuclein and astrocytes to the development and progression of Parkinson's disease, as well as to evaluate recent therapeutic proposals specifically focused on synucleopathies and astroglial cells as potential therapies for the disease.