After initially emerging in China, the coronavirus (COVID-19) outbreak has advanced rapidly. The World Health Organization (WHO) has recently declared it a pandemic, with Europe becoming its new ...epicentre. Italy has so far been the most severely hit European country and demand for critical care in the northern region currently exceeds its supply. This raises significant ethical concerns, among which is the allocation of scarce resources. Professionals are considering the prioritisation of patients most likely to survive over those with remote chances, and this news has triggered an intense debate about the right of every individual to access healthcare. The proposed analysis suggests that the national emergency framework in which prioritisation criteria are currently enforced should not lead us to perceive scarce resources allocation as something new. From an ethical perspective, the novelty of the current emergency is not grounded in the devastating effects of scarce resources allocation, which is rife in recent and present clinical practice. Rather, it has to do with the extraordinarily high number of people who find themselves personally affected by the implications of scarce resources allocation and who suddenly realise that the principle of ‘equals should be treated equally’ may no longer be applicable. Along with the need to allocate appropriate additional financial resources to support the healthcare system, and thus to mitigate the scarcity of resources, the analysis insists on the relevance of a medical ethics perspective that does not place the burden of care and choice solely on physicians.
The term “biobanking” is often misapplied to any collection of human biological materials (biospecimens) regardless of requirements related to ethical and legal issues or the standardization of ...different processes involved in tissue collection. A proper definition of biobanks is large collections of biospecimens linked to relevant personal and health information (health records, family history, lifestyle, genetic information) that are held predominantly for use in health and medical research. In addition, the International Organization for Standardization, in illustrating the requirements for biobanking (ISO 20387:2018), stresses the concept of biobanks being legal entities driving the process of acquisition and storage together with some or all of the activities related to collection, preparation, preservation, testing, analysing and distributing defined biological material as well as related information and data. In this review article, we aim to discuss the basic principles of biobanking, spanning from definitions to classification systems, standardization processes and documents, sustainability and ethical and legal requirements. We also deal with emerging specimens that are currently being generated and shaping the so-called next-generation biobanking, and we provide pragmatic examples of cancer-associated biobanking by discussing the process behind the construction of a biobank and the infrastructures supporting the implementation of biobanking in scientific research.
Decentralized clinical trials (DCTs) are studies in which the need for patients to physically access hospital-based trial sites is reduced or eliminated. The CoViD-19 pandemic has caused a ...significant increase in DCT: a survey shows that 76% of pharmaceutical companies, device manufacturers, and Contract Research Organizations adopted decentralized techniques during the early phase of the pandemic. The implementation of DCTs relies on the use of digital tools such as e-consent, apps, wearable devices, Electronic Patient-Reported Outcomes (ePRO), telemedicine, as well as on moving trial activities to the patient's home (e.g., drug delivery) or to local healthcare settings (i.e., community-based diagnosis and care facilities). DCTs adapt to patients' routines, allow patients to participate regardless of where they live by removing logistical barriers, offer better access to the study and the investigational product, and permit the inclusion of more diverse and more representative populations. The feasibility and quality of DCTs depends on several requirements including dedicated infrastructures and staff, an adequate regulatory framework, and partnerships between research sites, patients and sponsors. The evaluation of Ethics Committees (ECs) is crucial to the process of innovating and digitalizing clinical trials: adequate assessment tools and a suitable regulatory framework are needed for evaluation by ECs. DCTs also raise issues, many of which are of considerable ethical significance. These include the implications for the relationship between patients and healthcare staff, for the social dimension of the patient, for data integrity (at the source, during transmission, in the analysis phase), for personal data protection, and for the possible risks to health and safety. Despite their considerable growth, DCTs have only received little attention from bioethicists. This paper offers a review on some ethical implications and requirements of DCTs in order to encourage further ethical reflection on this rapidly emerging field.
Cancer is the second leading cause of death in developed countries, making it a global public health problem. In this scenario, early detection is the key to successful treatment. Tissue biopsy, the ...current gold standard for cancer diagnosis, offers reliable results, but it is feasible only when the mass becomes detectable. On the other hand liquid biopsy, a promising experimental system, not yet implemented within clinical practice, allows early detection as its functioning relies on the analysis of body fluids. Yet, its results are less reliable if compared to those of tissue biopsy as, for instance, false positives and false negatives might occur. Despite technical features, the tradeoff between a reliable diagnosis available at a later time and a potentially less reliable diagnosis available at an early stage poses significant ethical challenges in the clinical scenario which involve, among other aspects, informed consent, communication, and patient-physician encounter.
Phytoestrogens, polyphenolic compounds derived from plants, are more and more common constituents of human and animal diets. In most of the cases, these chemicals are much less potent than endogenous ...estrogens but exert their biological effects via similar mechanisms of action. The most common source of phytoestrogen exposure to humans as well as ruminants is soybean-derived foods that are rich in the isoflavones genistein and daidzein being metabolized in the digestive tract to even more potent metabolites—para-ethyl-phenol and equol. Phytoestrogens have recently come into considerable interest due to the increasing information on their adverse effects in human and animal reproduction, increasing the number of people substituting animal proteins with plant-derived proteins. Finally, the soybean becomes the main source of protein in animal fodder because of an absolute prohibition of bone meal use for animal feeding in 1995 in Europe. The review describes how exposure of soybean-derived phytoestrogens can have adverse effects on reproductive performance in female adults.
The identification of reproductive toxicants is a major scientific challenge for human health. Prenatal life is the most vulnerable and important time span of human development. For obvious ethical ...reasons, in vivo models cannot be used in human pregnancy, and animal models do not perfectly reflect human physiology. This review describes the in vitro test models representative of the human feto–maternal interface and the effects of environmental chemicals with estrogen-like activity, mainly bisphenol A and para-nonylphenol, with a particular emphasis on the effects at low, nontoxic doses similar to concentrations commonly detected in the population.
•Nicotine reduces proliferation of BeWo cells without affecting cell viability.•Nicotine increases the expression of ER-stress related GRP78/BiP protein.•Nicotine and ethanol increase ROS ...production.•Nicotine and ethanol induce changes in stress response-related MAPK proteins.
Human placental trophoblastic cancer BeWo cells can be used as a model of placental trophoblasts. We found that combined exposure to relevant exposure concentrations of ethanol (2‰) and nicotine (15μM) induces an increase in the amount of reactive oxygen species (ROS). Neither ethanol or nicotine alone, nor their combination affected cell viability. However, nicotine decreased cell proliferation, both alone and combined with ethanol. Nicotine increased the expression of the endoplasmic reticulum (ER)-stress related protein GRP78/BiP, but not another marker of ER-stress, IRE1α. We also studied the effects of nicotine and/or ethanol on phosphorylation and expression of three mitogen-activated protein kinases (MAPKs), i.e. JNK, p38 and ERK1/2. Nicotine decreased the phosphorylation of JNK and also had similar effect on total amount of this protein. Phosphorylation and expression of p38 were increased 1.7- and 1.6-fold, respectively, by nicotine alone, and 1.9- and 2.1-fold by the combined treatment. Some increase (1.8-fold) was also seen in the phosphorylation of ERK2 at 48h, in cells exposed to both ethanol and nicotine. This study shows that ethanol and nicotine, which harm the development of fetus may induce both oxidative and ER stress responses in human placental trophoblastic cells, implicating these mechanisms in their fetotoxic effects.
According to Law 91/1999, art. 18, in Italy, health care professionals and administrative staff involved in the process of organ collection and transplantation are required to ensure anonymity of ...both the donor and the recipient. Against this backdrop, in 2018, the Italian Committee for Bioethics (ICB) released an official opinion titled “Opinion on the preservation of the anonymity of donor and receiver in the transplantation of organs” that offers a new perspective on the topic, effectively opening the possibility of anonymity ending at certain conditions. The relevance of anonymity within the transplant network is a globally recognized principle with a strong ethical value. In this article, based on the experience of one author directly involved in the ICB opinion drafting, we examine the document and discuss how such a proposal could be implemented at the legislative level.
•Italian regulations require anonymity between the family of the deceased donor and the recipient.•According to the ICB, identification could be possible if both parties express an intention to come into contact with each other.•Any contact between the donor’s family and recipient must be managed by a third-party body pertaining to the National Health Service.
•Bisphenol A and para-nonylphenol affect human placenta development at concentrations detected in human tissues and fluids.•BPA and p-NP decreased trophoblast cell migration and invasion and ...trophoblast/endothelial interaction.•BPA and p-NP induced differentiation of trophoblast into placental bed giant cells.•BPA and p-NP act on trophoblast cells in a dose-dependent manner.
Bisphenol A (BPA) and para-Nonylphenol (p-NP) are chemicals of industrial origin which may influence human reproductive health. The effects of these substances in the prenatal life is an important topic that is receiving greater attention in the developed countries. In this study, human trophoblast cells HTR-8/SVneo were exposed to BPA and p-NP (1 × 10−15, 1 × 10−13, 1 × 10−11, 1 × 10−9 and 1 × 10−7 M) and incubated for 24, 48 and/or 72 h then, examined for the main physiological processes which characterize the extravillous trophoblast. Cell proliferation showed no changes while the processes of cell migration and invasion were both reduced by BPA and p-NP. For each chemical, the activity was higher at lower concentrations with a maximum activity between 1 × 10−13 and 1 × 10−11 M (p < 0.05 for 1 × 10−9 and p < 0.001 for 1 × 10−11 M). Co-culture studies with human umbilical cord endothelial cells (HUVEC) revealed that trophoblast/endothelial interaction was significantly reduced by p-NP at 1 × 10−11 M. Moreover, both chemicals were inducing differentiation of HTR-8/SVneo toward polyploidy by the process of endoreduplication. The estrogen-receptor antagonist ICI significantly reduced p-NP action, while it had no effect on BPA treated cells. In conclusion, p-NP and BPA act on trophoblast cells altering key physiological processes in placenta development. The exact mechanism of action of the chemicals in human trophoblast still needs to be clarified.
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