In their article ’Is Pregnancy a Disease? A Normative Approach’, Anna Smajdor and Joona Räsänen contend that, on several of the most prominent accounts of disease, pregnancy should be considered a disease. More specifically, of the five accounts they discuss, each renders pregnancy a disease or suffers serious conceptual problems otherwise. They take issue specifically with the dysfunction account of disease and argue that it suffers several theoretical difficulties. In this response, we focus on defending (...) the dysfunction account against their main objections and show why a version of the dysfunction account is viable on account of the indispensability of normativity in biology and medicine. After disarming their main objections to the dysfunction account, we briefly respond to their treatment of the normality of pregnancy and then draw a distinction between adverse symptoms and underlying causes to show why even though pregnancy may have ’disease-like’ features, it is not a disease. (shrink)

. Recent philosophers of science have not only revived the classical argument from inductive risk but extended it. I argue that some of the purported extensions do not fit cleanly within the schema of the original argument, and I discuss the problem of overdiagnosis of disease due to expanded disease definitions in order to show that there are some risks in the research process that are important and that very clearly fall outside of the domain of inductive risk. (...) Finally, I introduce the notion of epistemic risk in order to characterize such risks. (shrink)

On the basis of the evidence that tumor development is suppressed by the embryonic microenvironment, some experiments using the factors taken from Zebrafish embryo at precise stages of cell differentiation were made. These experiments demonstrated a significant growth inhibition on different tumor cell lines in vitro. The observed mechanism of tumor growth inhibition is connected with the key-role cell cycle regulation molecules, such as p53 and pRb, which are modified by transcriptional or post-translational processes. Research on apoptosis and differentiation revealed (...) that treatment with these factors induces caspase-3 with a p73 apoptotic-dependent pathway activation and a concurrent significant normalization of e-cadherin and beta-catenin ratio. Other experiments found a synergistic effect on the colon cancer proliferation curve after the concurrent treatment with these factors and 5-fluorouracil. Finally, a product prepared for human therapy demonstrated 19.8% regression and 16% stable disease in an... (shrink)

'The Patient as Victim and Vector' is jointly written by four authors at the University of Utah with expertise in bioethics health law, and both clinical practice and public health policy concerning infectious disease.

Biological dysfunction is regarded, in many accounts, as necessary and perhaps sufficient for disease. But although disease is conceptualized as all-or-nothing, biological functions often differ by degree. A tension is created by attempting to use a continuous variable as the basis for a categorical definition, raising questions about how we are to pinpoint the boundary between health and disease. This is the line-drawing problem. In this paper, we show how the line-drawing problem arises within “dysfunction-requiring” accounts of (...) disease, such as those of Christopher Boorse and Jerome Wakefield. We then provide several detailed examples to establish that biological dysfunction cannot provide a boundary. We examine potential ways of resolving the line-drawing problem, either by dropping one of the claims that generates it, or by appealing to additional criteria. We argue that two of these options are plausible, and that each of these can be applied with regard to different diseases. (shrink)

Anna Smajdor and Joona Räsänen argue that we have good reason to classify pregnancy as a disease. They discuss five accounts of disease and argue that each account either implies that pregnancy is a disease or, if it does not, it faces problems. This strategy allows Smajdor and Räsänen to avoid articulating their own account of disease. Consequently, they cannot establish that pregnancy is a disease, only that plausible accounts of disease suggest this. Some (...) readers will dismiss Smajdor and Räsänen’s claims as counterintuitive. By analogy, if a mathematical proof concludes ‘2+2=5’, readers will know—without investigation—that an error occurred. Rather than dismiss Smajdor and Räsänen’s work, however, the easiest way to undermine their argument is to describe at least one plausible account of disease that (i) excludes pregnancy and (ii) avoids the problems they raise for it. This is our strategy. We focus on dysfunction accounts of disease. After outlining Smajdor and Räsänen’s main arguments against dysfunction accounts, we explain why pregnancy is not a disease on these accounts. Next, we defend dysfunction accounts against the three problems that Smajdor and Räsänen raise. If successful, then contra Smajdor and Räsänen, at least one plausible account of disease does not imply that pregnancy is a disease. We suspect that defenders of other accounts can respond similarly. Yet, we note that insofar as dysfunction accounts align with the commonsense intuition that pregnancy is not a disease, this, all else being equal, seems like a point in their favour. (shrink)

Given recent advancements in CRISPR‐Cas9 powered genetic modification of gametes and embryos, both popular media and scientific articles are hailing CRISPR’s life‐saving, curative potential for people with serious monogenic diseases. But claims that CRISPR modification of gametes or embryos, a form of germline engineering, has therapeutic value are deeply mistaken. This article explains why reproductive uses of CRISPR, and germline engineering more generally, do not treat or save lives that would otherwise have a genetic disease. Reproductive uses of CRISPR (...) create healthy people whose existence is not inevitable in the first place. Creating healthy lives has distinct and lesser moral value from saving or curing lives that would otherwise have genetic disease. The real value in reproductive uses of CRISPR is in helping a very limited population of people have healthy, genetically related children. This diminished value cannot compete with the concerns in opposition to germline engineering, nor is it worth the investment of research money. (shrink)

I review the brain disease model of addiction promoted by medical, scientific, and clinical authorities in the US and elsewhere. I then show that the disease model is flawed because brain changes in addiction are similar to those generally observed when recurrent, highly motivated goal seeking results in the development of deep habits, Pavlovian learning, and prefrontal disengagement. This analysis relies on concepts of self-organization, neuroplasticity, personality development, and delay discounting. It also highlights neural and behavioral parallels between (...) substance addictions, behavioral addictions, normative compulsive behaviors, and falling in love. I note that the short duration of addictive rewards leads to negative emotions that accelerate the learning cycle, but cortical reconfiguration in recovery should also inform our understanding of addiction. I end by showing that the ethos of the disease model makes it difficult to reconcile with a developmental-learning orientation. (shrink)

Human-Computer Interaction and games set a new domain in understanding people’s motivations in gaming, behavioral implications of game play, game adaptation to player preferences and needs for increased engaging experiences in the context of HCI serious games. When the latter relate with people’s health status, they can become a part of their daily life as assistive health status monitoring/enhancement systems. Co-designing HCI-SGs can be seen as a combination of art and science that involves a meticulous collaborative process. The design elements (...) in assistive HCI-SGs for Parkinson’s Disease patients, in particular, are explored in the present work. Within this context, the Game-Based Learning design framework is adopted here and its main game-design parameters are explored for the Exergames, Dietarygames, Emotional games, Handwriting games, and Voice games design, drawn from the PD-related i-PROGNOSIS Personalized Game Suite holistic approach. Two main data sources were involved in the study. In particular, the first one includes qualitative data from semi-structured interviews, involving 10 PD patients and four clinicians in the co-creation process of the game design, whereas the second one relates with data from an online questionnaire addressed by 104 participants spanning the whole related spectrum, i.e., PD patients, physicians, software/game developers. Linear regression analysis was employed to identify an adapted GBL framework with the most significant game-design parameters, which efficiently predict the transferability of the PGS beneficial effect to real-life, addressing functional PD symptoms. The findings of this work can assist HCI-SG designers for designing PD-related HCI-SGs, as the most significant game-design factors were identified, in terms of adding value to the role of HCI-SGs in increasing PD patients’ quality of life, optimizing the interaction with personalized HCI-SGs and, hence, fostering a collaborative human-computer symbiosis. (shrink)

In The Biopsychosocial Model of Health and Disease, Derek Bolton and Grant Gillett argue that a defensible updated version of the biopsychosocial model requires a metaphysically adequate account of disease causation that can accommodate biological, psychological, and social factors. This present paper offers a philosophical critique of their account of biopsychosocial causation. I argue that their account relies on claims about the normativity and the semantic content of biological information that are metaphysically contentious. Moreover, I suggest that these (...) claims are unnecessary for a defence of biopsychosocial causation, as the roles of multiple and diverse factors in disease causation can be readily accommodated by a more widely accepted and less metaphysically contentious account of causation. I then raise the more general concern that they are misdiagnosing the problem with the traditional version of the biopsychosocial model. The challenge when developing an explanatorily valuable version of the biopsychosocial model, I argue, is not so much providing an adequate account of biopsychosocial causation, but providing an adequate account of causal selection. Finally, I consider how this problem may be solved to arrive at a more explanatorily valuable and clinically useful version of the biopsychosocial model. (shrink)

In this paper, we present and defend the theoretical framework of an empirical model to describe people’s fundamental moral attitudes (FMAs) to animals, the stratification of FMAs in society and the role of FMAs in judgment on the culling of healthy animals in an animal disease epidemic. We used philosophical animal ethics theories to understand the moral basis of FMA convictions. Moreover, these theories provide us with a moral language for communication between animal ethics, FMAs, and public debates. We (...) defend that FMA is a two-layered concept. The first layer consists of deeply felt convictions about animals. The second layer consists of convictions derived from the first layer to serve as arguments in a debate on animal issues. In a debate, the latter convictions are variable, depending on the animal issue in a specific context, time, and place. This variability facilitates finding common ground in an animal issue between actors with opposing convictions. (shrink)

Developmental origins of health and disease and epigenetics have expanded understanding of how the environment affects the health of women before and during pregnancy—with lifelong health consequences for the fetus. This has translated to a narrow focus on women’s lifestyle during pregnancy, especially for women classified as obese. In this study, we show that psychosocial harms such as distress or shame felt by pregnant women are rarely countenanced in these endeavors. To demonstrate this, we examine published documents about a (...) large set of trials of lifestyle interventions united through an international consortium. Yet there is now a literature in which pregnant women with large bodies report feeling humiliated and a wider literature on the stigma of obesity. We argue that shame is produced and reproduced through the discursive and material knowledge-making scientific practices of DOHaD translation. Interventions that intensify the shame of large body size in pregnancy may be stressful, and neurophysiological stress pathways are well-known within DOHaD to have consequences for fetal development, so these interventions potentially undermine the very processes they set out to protect. A feminist response may protect women from shame and redirect attention to the social and structural determinants of health. (shrink)

Free will has been the object of debate in the context of addiction given that addiction could compromise an individual’s ability to choose freely between alternative courses of action. Proponents of the brain-disease model of addiction have argued that a neuroscience perspective on addiction reduces the attribution of free will because it relocates the cause of the disorder to the brain rather than to the person, thereby diminishing the blame attributed to the person with an addiction. Others have worried (...) that such displacement of free will attribution would make the person with a drug addiction less responsible. Using the paradigmatic literature on the seductive allure of neuroscience explanations, we tested whether neuroscience information diminishes attributions of free will in the context of addiction and whether respondent characteristics influence these attributions and modulate the effect of neuroscience information. We performed a large-scale, web-based experiment with 2,378 German participants to explore how attributions of free will in the context of addiction to either alcohol or cocaine are affected by: (1) a text with a neurobiological explanation of addiction, (2) a neuroimage showing effects of addiction on the brain, and (3) a combination of a text and a neuroimage, in comparison to a control group that received no information. Belief in free will was measured using the FAD-Plus scale and was, subsequent to factor analysis, separated into two factors: responsibility and volition. The investigated respondent characteristics included gender, age, education, self-reported knowledge of neuroscience, substance-use disorder (SUD), and having a friend with SUD. We found that attributions of volition (in the cocaine-subsample) were reduced in the text and neuroimage-treatment compared to the control group. However, respondent characteristics such as education and self-reported knowledge of neuroscience were associated with lower attributions of responsibility for both substances, and education was associated with lower attribution of volition for the alcohol sub-sample. Interaction analyses showed that knowledge of neuroscience was found to generally decrease attribution of responsibility. Further research on attribution of free will should consider the effects of context and respondent characteristics, which appeared surprisingly larger than those induced by experimental treatments. (shrink)

ABSTRACT The use of broad consent for genomics research raises important ethical questions for the conduct of genomics research, including relating to its acceptability to research participants and comprehension of difficult scientific concepts. To explore these and other challenges, we conducted a study using qualitative methods with participants enrolled in an H3Africa Rheumatic Heart Disease genomics study (the RHDGen network) in Zambia to explore their views on broad consent, sample and data sharing and secondary use. In-depth interviews were conducted (...) with RHDGen participants (n = 18), study staff (n = 5) and with individuals who refused to participate (n = 3). In general, broad consent was seen to be reasonable if reasons for storing the samples for future research use were disclosed. Some felt that broad consent should be restricted by specifying planned future studies and that secondary research should ideally relate to original disease for which samples were collected. A few participants felt that broad consent would delay the return of research results to participants. This study echoes findings in other similar studies in other parts of the continent that suggested that broad consent could be an acceptable consent model in Africa if careful thought is given to restrictions on re-use. (shrink)

Three negative affective dispositions—anger, anxiety, and depression—are hypothesized to increase physical disease risk and have been the subject of epidemiological studies. However, the overlap among the major negative affective dispositions, and the superordinate construct of trait negative affectivity are only beginning to be tested. Presented here is a narrative review of recent prospective studies that simultaneously tested anger, anxiety, depression, and trait NA as risk factors for cardiac outcomes. Anxiety and depression emerged as independent risk factors for premature heart (...) disease in population studies of persons nominally healthy at baseline, and for recurrence/mortality among patients with existing heart disease. General trait NA also was a cardiac risk factor in population samples. (shrink)

In the Global Burden of Disease study, disease burden is measured as disability-adjusted life years (DALYs). The paramount assumption of the DALY is that it makes sense to aggregate years lived with disability (YLDs) and years of life lost (YLLs). However, this is not smooth sailing. Whereas morbidity (YLD) is something thathappens toan individual, loss of life itself (YLL) occurs when that individual’s life has ended. YLLs quantify something that involves no experience and does not take place among (...) living individuals. This casts doubt on whether the YLL is an individual burden at all. If not, then YLDs and YLLs are incommensurable. There are at least three responses to this problem, only one of which is tenable: a counterfactual account of harm. Taking this strategy necessitates a re-examination of how we count YLLs, particularly at the beginning of life. (shrink)

Social media applications such as Twitter, YouTube and Facebook have attained huge popularity, with more than three billion people and organizations predicted to have a social networking account by 2015. Social media offers a rapid avenue of communication with the public and has potential benefits for communicable disease control and surveillance. However, its application in everyday public health practice raises a number of important issues around confidentiality and autonomy. We report here a case from local level health protection where (...) the friend of an individual with meningococcal septicaemia used a social networking site to notify potential contacts. (shrink)

In the last decades it has become clear that medicine must find some way to combine its scientific and humanistic sides. In other words, an adequate notion of medicine requires an integrative position that mediates between the analytic-reductionist and the normative-holistic tendencies we find therein. This is especially important as these different styles of reasoning separate “illness” (something perceived and managed by the whole individual in concert with their environment) and “disease” (a “mechanical failure” of a biological element within (...) the body). While the demand for an integrative view has typically been motivated by ethical concerns, we claim that it is also motivated, perhaps even more fundamentally, by epistemological and methodological reasons. Evidence-based bio-medicine employs experimental and statistical techniques which eliminate important differences in the ways that conscious humans evaluate, live with, and react to disease and illness. However, it is precisely these experiences that underpin the concepts and norms of bio-medicine. Humanistic disciplines, on the other hand, have the resources to investigate these experiences in an intersubjectively testable way. Medicine, therefore, cannot afford to ignore its nature as a human science; it must be concerned not only with disease and illness, but also with the ways in which patients as persons respond to malady. Insofar as attitudes and expectations influence the criteria of illness and disease, they must be studied as part of the genuine subject matter of medicine as a human science. In general, we urge that this is a necessary step to overcome today's trend to split evidence-based and clinical medicine. (shrink)

What is the relationship between harm and disease? Discussions of the relationship between harm and disease typically suffer from two shortcomings. First, they offer relatively little analysis of the concept of harm itself, focusing instead on examples of clear cases of harm such as death and dismemberment. This makes it difficult to evaluate such accounts in borderline cases, where the putative harms are less severe. Second, they assume that harm-based accounts of disease must be understood normatively rather (...) than naturalistically, in the sense that they are inherently value based. This makes such accounts vulnerable to more general objections of normative accounts of disease. Here we draw on an influential account of harm from the philosophy of law to develop a harm-based account of disease that overcomes both of these shortcomings. (shrink)

ABSTRACT A key selling point of pharmacogenetics is the genetic stratification of either patients or diseases in order to target the prescribing of medicine. The hope is that genetically ‘tailored’ medicines will replace the current ‘one‐size‐fits‐all’ paradigm of drug development and usage. This paper is concerned with the relationship between difference and justice in the use of pharmacogenetics. This new technology, which facilitates the identification and use of difference, has, we shall argue, the potential to lead to injustice either by (...) the inappropriate use of difference or through the inappropriate failure to use difference. We build on empirical data from a detailed study of the range of options for the development of pharmacogenetics to present a consideration of the ethical issues that surround patient and disease stratification. In it we explore the ways in which the use of pharmacogenetics may lead to the creation of new, genetically stratified, forms of difference and new forms of injustice based on these divisions. We also examine the ways in which existing forms of difference and social stratification may interact with the use of pharmacogenetics. In conclusion, we suggest how an understanding of these ethical issues could usefully inform future policy discussions. (shrink)

The use of broad consent for genomics research raises important ethical questions for the conduct of genomics research, including relating to its acceptability to research participants and comprehension of difficult scientific concepts. To explore these and other challenges, we conducted a study using qualitative methods with participants enrolled in an H3Africa Rheumatic Heart Disease genomics study in Zambia to explore their views on broad consent, sample and data sharing and secondary use. In-depth interviews were conducted with RHDGen participants, study (...) staff and with individuals who refused to participate. In general, broad consent was seen to be reasonable if reasons for storing the samples for future research use were disclosed. Some felt that broad consent should be restricted by specifying planned future studies and that secondary research should ideally relate to original disease for which samples were collected. A few participants felt that broad consent would delay the return of research results to participants. This study echoes findings in other similar studies in other parts of the continent that suggested that broad consent could be an acceptable consent model in Africa if careful thought is given to restrictions on re-use. (shrink)

This paper extends previous arguments against the assumption that the study of variation at the molecular level was instigated with a view to solving an internal conflict between the balance and classical schools of population genetics. It does so by focusing on the intersection of basic research in protein chemistry and the molecular approach to disease with the enactment of global health campaigns during the Cold War period. The paper connects advances in research on protein structure and function as (...) reflected in Christian Anfinsen’s The molecular basis of evolution, with a political reading of Emilé Zuckerkandl and Linus Pauling’s identification of molecular disease and evolution. Beyond atomic fallout, these advances constituted a rationale for the promotion of genetic surveys of human populations in the Third World, in connection with international health programs. Light is shed not only on the experimental roots of the molecular challenge but on the broader geopolitical context where the rising role of biomedicine and public health had an impact on evolutionary biology. (shrink)

We situate the well-trodden debate about defining health and disease within the project of a metaphysics of science and its aim to work with and contribute to science. We make use of Guay and Pradeu’s ‘metaphysical box’ to reframe this debate, showing what is at stake in recent attempts to move beyond it, revealing unforeseen points of agreement and disagreement among new and old positions, and producing new questions that may lead to progress. We then discuss the implications of (...) the two-way benefits between medicine and philosophy when the latter is driven and constrained by medical science. (shrink)

People struggling with addiction are neither powerless over their addiction, nor are they fully in control. Lewis vigorously objects to the brain disease model of addiction, because it makes people lose belief in their self-efficacy, and hence hinders their recovery. Although he acknowledges that there is a compulsive state in addiction, he objects to the claim that this compulsion is carved in stone. Lewis argues that the BDMA underestimates the agency of addicted people, and hence hinder their recovery. Lewis’s (...) work offers us a very much to be welcomed neurobiology of recovery. It offers addicted people a hopeful and respectful narrative for their recovery that treats them as agents rather than as damaged brains. However, I argue that overestimating people’s agency can also result in people losing belief in their self-efficacy. Lewis’s strong focus on the agency of addicted people might not match their experiences of struggle, hence reinforcing their feelings of guilt when they fail to control their use. I propose to replace the notion of addiction as a disease with a notion of a disease-like stage in addiction. I call this stage the duress stage in addiction, in which the addictive behaviour is largely impervious to the agent’s values and to available techniques of self-control. However, the agent can overcome this stage by developing new techniques of self-control, by building on their self-concept and belief in self-efficacy, by changing their environments and habits, and by engaging in projects that are meaningful to the agent. (shrink)

The new Coronavirus has been declared a global pandemic by the World Health Organization. The sudden outbreak of this new virus and the measure of lockdown adopted to contain the epidemic have profoundly changed the lifestyles of the Italian population, with an impact on people’s quality of life and on their social relationships. In particular, due to forced and prolonged cohabitation, couples may be subject to specific stressors during the epidemic. In addition, living with a chronic health condition may add (...) specific challenges to the ones posed by the epidemic itself. The present cross-sectional study aimed to provide a picture of the challenges as well as the resources for both individual and relational well-being of Italian individuals in a couple relationship, with a specific attention to the comparison between individuals living with and without a chronic disease. Results showed that people with a chronic disease had lower psychological well-being and more fears and worries about the COVID-19. People with a chronic disease perceived fewer resources than healthy people. Moreover, the challenges are shown to be associated with less psychological well-being and high pessimism about the future. Instead individual, relational, and social resources play a protective role during the pandemic for both healthy and chronically ill people. (shrink)

Antimicrobial resistance (AMR) is a global public health disaster driven largely by antibiotic use in human health care. Doctors considering whether to prescribe antibiotics face an ethical conflict between upholding individual patient health and advancing public health aims. Existing literature mainly examines whether patients awaiting consultations desire or expect to receive antibiotic prescriptions, but does not report views of the wider public regarding conditions under which doctors should prescribe antibiotics. It also does not explore the ethical significance of public views (...) or their sensitivity to awareness of AMR risks or the standpoint (self-interested or impartial) taken by participants. Methods: An online survey was conducted with a sample of the U.S. public (n = 158). Participants were asked to indicate what relative priority should be given to individual patients and society-at-large from various standpoints and in various contexts, including antibiotic prescription. Results: Of the participants, 50.3% thought that doctors should generally prioritize individual patients over society, whereas 32.0% prioritized society over individual patients. When asked in the context of AMR, 39.2% prioritized individuals whereas 45.5% prioritized society. Participants were significantly less willing to prioritize society over individuals when they themselves were the patient, both in general (p = .001) and in relation to AMR specifically (p = .006). Conclusions: Participants’ attitudes were more oriented to society and sensitive to collective responsibility when informed about the social costs of antibiotic use and when considered from a third-person rather than first-person perspective. That is, as participants came closer to taking the perspective of an informed and impartial “ideal observer,” their support for prioritizing society increased. Our findings suggest that, insofar as antibiotic policies and practices should be informed by attitudes that are impartial and well-informed, there is significant support for prioritizing society. (shrink)

Biology is the study of life, psychology is the study of mind, and medicine is the investigation of the causes and treatments of disease. This chapter describes how the central concepts of life, mind, and disease have undergone fundamental changes in the past 150 years or so. There has been a progression from theological, to qualitative, to mechanistic explanations of the nature of life, mind and disease. This progression has involved both theoretical change, as new theories with (...) greater explanatory power replaced older ones, and emotional change as the new theories brought reorientation of attitudes toward the nature of life, mind, and disease. After a brief comparison of theological, qualitative, and mechanistic explanations, I will describe how shifts from one kind of explanation to another have carried with them dramatic kinds of conceptual change in the key concepts in the life sciences. Three generalizations follow about the nature of conceptual change in the history of science: there has been a shift from conceptualizations in terms of simple properties to ones in terms of complex relations; conceptual change is theory change; and conceptual change is often emotional as well as cognitive. The contention that historical development proceeds in three stages originated with the nineteenth-century French philosophers, Auguste Comte, who claimed that November 9, 2006 human intellectual development progresses from a theological to a “metaphysical” stage to a “positive” (scientific) stage (Comte, 1988). The stages I have in mind are different from Comte’s, so let me say what they involve. By the theological stage I mean systems of thought in which the primary explanatory entities are supernatural ones beyond the reach of science, such as gods, devils, angels, spirits, and souls. For example, the concept of fire was initially theological, as in the Greek myth of Prometheus receiving fire from the gods.. (shrink)

The theory stating that oxidative stress is at the root of several diseases is extremely popular. However, so far, no antioxidant is recommended or offered by healthcare systems neither approved as therapy by regulatory agencies that base their decisions on evidence-based medicine. This is simply because, so far, despite many preclinical and clinical studies indicating a beneficial effect of antioxidants in many disease conditions, randomised clinical trials have failed to provide the evidence of efficacy required for drug approval. In (...) this review, we discuss the levels of evidence required to claim causality in preclinical research on OS, the weakness of the oversimplification associated with OS theory of disease and the importance of the narrative in its popularity. Finally, from a more translational perspective, we discuss the reasons why antioxidants acting by scavenging reactive oxygen species might not only prevent their detrimental effects but also interfere with essential signalling roles. We propose that ROS have a complex metabolism and are generated by different enzymes at diverse sites and with different timing. Aggregating this plurality of systems in a single theory of disease may not be the best way to develop new drugs, and future research may need to focus on specific oxygen-toxifying pathways rather than on non-specific ROS scavengers. Finally, similarly to what is nowadays required for clinical trials, we recommend making unpublished data available in repositories, as this will allow big data approaches or meta-analyses without the blinders of the publication bias. (shrink)

This paper constitutes a defence of the basic philosophical enterprise of characterising concepts such as disease and health, as well as other medical concepts. I argue that these concepts play important roles, not only in medical, but also in other scientific and social contexts. In particular, medical decisions about health and diseasehood have important ethical, social and economic consequences. The role played is, however, not always a rational one. But the greater is the need for a reconstruction of this (...) network of concepts for the purpose of efficient and rational communication. (shrink)

Alzheimer’s disease (AD) may be situated within a cultural landscape produced, in part, by demographics and the marketing strategies of an aggressive biopharmaceutical industry. The simultaneously corporeal and visual domain of advertisements for anti-AD drugs generates dynamic images of gender and embodiment, and it also lends itself to feminist interventions engaging with the images and ideas circulating around aging, medicine and the body. In this article, we investigate advertisements targeting medical practitioners treating patients with AD. Working within a methodological (...) framework we identify as ‘feminist visual studies of technoscience’, we want to propel the discussion in the direction of a broader corpus of medical media. Through this limited exercise, we hope to make a scholarly contribution to the feminist community by critiquing some of the images emerging within popular/scientific media with regard to Alzheimer’s, a disease collectively imagined within an aging Western population. (shrink)

This paper analyses self-declared aims and representation of dementia patient organizations and advocacy groups in relation to two recent upheavals: the critique of social stigmatization and biomedical research focusing on prediction. Based on twenty-six semi-structured interviews conducted in 2016–2017 with members, service recipients, and board representatives of POs in Germany and Israel, a comparative analysis was conducted, based on a grounded theory approach, to detect emerging topics within and across the POs and across national contexts. We identified a heterogeneous landscape, (...) with the only Israeli PO focusing strongly on caretakers, whereas in Germany several POs claim to represent this patient collective. Shared aims of all POs were fighting social stigma, balancing the loss of patients’ individual autonomy, and the well-being of caretakers. By highlighting the emergence of new groups of dementia self-advocacy against the more traditional advocacy by others, this study highlights how advocacy and representation in the context of AD are embedded in the discursive context of stigmatization and revised disease conception. Future developments in early diagnosis and prediction of dementia, with more affected people likely to conduct dementia self-advocacy, might challenge existing representation structures even more. (shrink)

The question of whether medical and psychiatric judgements involve a normative or evaluative component has been a source of wide and vehement disagreement. But among those who think such a component is involved, there is considerable further disagreement as to its nature. In this article, I consider several versions of Aristotelian normativism, as propounded by Christopher Megone, Michael Thompson and Philippa Foot, and Martha Nussbaum. The first two, I claim, can be persuasively rebutted by different modes of liberal pluralist challenge (...) — respectively, pluralism about structures of social organisation and pluralism about biological forms. Nussbaum's version, by contrast, is alert to the need for pluralism; I argue, however, that the Aristotelian aspects of her theory hamper her pursuit of those pluralistic aims. (shrink)

The Swiss-born medical researcher Karl Friedrich Meyer is best known as a ‘microbe hunter’ who pioneered investigations into diseases at the intersection of animal and human health in California in the 1920s and 1930s. In particular, historians have singled out Meyer’s 1931 Ludwig Hektoen Lecture in which he described the animal kingdom as a ‘reservoir of disease’ as a forerunner of ‘one medicine’ approaches to emerging zoonoses. In so doing, however, historians risk overlooking Meyer’s other intellectual contributions. Developed in (...) a series of papers from the mid-1930s onwards, these were ordered around the concept of latent infections and sought to link microbial behavior to broader bio-ecological, environmental, and social factors that impact hostpathogen interactions. In this respect Meyer—like the comparative pathologist Theobald Smith and the immunologist Frank Macfarlane Burnet—can be seen as a pioneer of modern ideas of disease ecology. However, while Burnet’s and Smith’s contributions to this scientific field have been widely acknowledged, Meyer’s have been largely ignored. Drawing on Meyer’s published writings and private correspondence, this paper aims to correct that lacuna while contributing to a reorientation of the historiography of bacteriological epidemiology. In particular I trace Meyer’s intellectual exchanges with Smith, Burnet and the animal ecologist Charles Elton, over brucellosis, psittacosis and plague—exchanges that not only showed how environmental and ecological conditions could ‘tip the balance’ in favor of parasites but which transformed Meyer thinking about resistance to infection and disease. (shrink)

The ongoing COVID-19 pandemic has brought science to the fore of public discourse and, considering the complexity of the issues involved, with it also the challenge of effective and informative science communication. This is a particularly contentious topic, in that it is both highly emotional in and of itself; sits at the nexus of the decision-making process regarding the handling of the pandemic, which has effected lockdowns, social behaviour measures, business closures, and others; and concerns the recording and reporting of (...) disease mortality. To clarify a point that has caused much controversy and anger in the public debate, the first part of the present article discusses the very fundamentals underlying the issue of causative attribution with regards to mortality, lays out the foundations of the statistical means of mortality estimation, and concretizes these by analysing the recording and reporting practices adopted in England and their widespread misrepresentations. The second part of the article is empirical in nature. I present data and an analysis of how COVID-19 mortality has been reported in the mainstream media in the UK and the USA, including a comparative analysis both across the two countries as well as across different media outlets. The findings clearly demonstrate a uniform and worrying lack of understanding of the relevant technical subject matter by the media in both countries. Of particular interest is the finding that with a remarkable regularity (????>0.998), the greater the number of articles a media outlet has published on COVID-19 mortality, the greater the proportion of its articles misrepresented the disease mortality figures. (shrink)

The history of the research on peptic ulcer disease is characterized by a premature abandonment of the bacterial hypothesis, which subsequently had its comeback, leading to the discovery of Helicobacter pylori – the major cause of the disease. In this paper we examine the received view on this case, according to which the primary reason for the abandonment of the bacterial hypothesis in the mid-twentieth century was a large-scale study by a prominent gastroenterologist Palmer, which suggested no bacteria (...) could be found in the human stomach. To this end, we employ the methodof digital textual analysis and study the literature on the etiology of PUD published in the decade prior to Palmer’s article. Our findings suggest that the bacterial hypothesis had already been abandoned before the publication of Palmer’s paper, which challenges the widely held view that his study played a crucial role in the development of this episode. In view of this result, we argue that the PUD case does not illustrate harmful effects of a high degree of information flow, as it has frequently been claimed in the literature on network epistemology. Moreover, we argue that alternative examples of harmful effects of a high degree of information flow may be hard to find in the history of science. (shrink)

Aldehyde dehydrogenase 2 (ALDH2) deficiency constitutes one of the most common hereditary enzyme deficiencies, affecting 35% to 40% of East Asians and 8% of the world population. It causes the well-known Asian Alcohol Flush Syndrome, characterized by facial flushing, palpitation, tachycardia, nausea, and other unpleasant feelings when alcohol is consumed. It is also associated with a marked increase in the risk of a variety of serious disorders, including esophageal cancer and osteoporosis. Our recent studies with murine models have demonstrated that (...) a one-time administration of an adeno-associated virus (AAV) gene transfer vector expressing the human ALDH2 coding sequence (AAVrh.10hALDH2) will correct the deficiency state and prevent alcohol-induced abnormalities of the esophagus and bone. If successful in humans, such strategy would reduce the increased risk-associated disorders such as esophageal cancer and osteoporosis, but also prevent the Asian Alcohol Flush Syndrome. This treatment thus raises ethical concerns: although it would potentially prevent fatal disease, it could also allow affected individuals to drink alcohol without suffering the Asian Alcohol Flush Syndrome and, hence, potentially enable personal destructive behavior. Here we explore the ethical arguments against the development of a gene therapy for ALDH2 deficiency and we find them wanting. We contend that development of such treatments is ethically appropriate and should be part and parcel of the solutions offered against the condition. (shrink)

Prior to the genomic sequencing era, the bible for those working in clinical genetics was McKusick’s Mendelian Inheritance in Man, which appeared in multiple editions between the 1960s and the late 1990s. This catalogue was organized according to general patterns of inheritance and focused on phenotypes. Beginning in the mid-1980s, it was replaced by Online Mendelian Inheritance in Man, a continuously updated catalogue documenting molecular relationships between genetic variation and phenotypic expression. This paper explores this resource’s evolution with attention to (...) how disease is distinguished from clinically irrelevant variation and how phenotypic similarities are captured in cases where there is no obvious genotypic association. It is argued that hybrid compromises are encoded into OMIM®; in addition to serving its key original purpose of being a diagnostic catalogue, it also began to record detectable variations in the genome even if they were not known to be associated with phenotypically visible disorders or even phenotypic variations. Although the impacts of geneticization have been well recognized, particularly in popular media, this example allows exploration of some of the historic, epistemic, and methodological causes that underlie tendencies toward disease geneticization in contemporary medicine, while highlighting that such gene-focused strategies may in fact be warranted in some contexts. (shrink)

Disease-mongering, or the medicalisation of aspects of daily life in an attempt to generate commercial profit for a party other than the person whose complaint is medicalised, is a newly recognized and legitimate source of concern for both consumers and deliverers of health care. The interest brought to this area by the academy has the potential to acknowledge and address the consequences of the practice. However, before disease-mongering can establish itself firmly as an area of scholarly concern, researchers (...) must understand that the critique is not just about identifying commercial intent, but also about naming the mechanism through which discourses of health, cure and self-management are positioned. In this paper, I argue that a critical reflection on the construction of disease concepts and the mongering of their cure must include discussions of the foundations of health and the clinical encounter. I identify a number of pivotal issues within these themes that should be explored in order to ensure an unambiguous and productive discussion of disease-mongering and its correlates. (shrink)

Healthcare workers carry a substantial risk of harm from infectious disease, particularly, but not exclusively, during outbreaks. More can be done by healthcare institutions to identify risks, quantify the current burden of preventable infectious disease amongst HCWs and identify opportunities for prevention. We suggest that institutional obligations should be clarified with respect to the mitigation of infectious disease risks to staff, and question the duty of HCWs to care while healthcare institutions persist with a reactive rather than (...) proactive attitude to infectious disease threats. (shrink)

Concerns about the possibility of a sharp rise in the prevalence of Alzheimer’s disease in Western nations have led to both the significant deployment of resources and the development of national research and healthcare plans. Although often focused on treatment, substantial efforts have also been dedicated toward preventing or delaying AD onset. As a result, recent technological and biomedical advances have greatly improved the understanding of AD pathophysiology. While some new tests can assess only risk ), some tests for (...) certain biomarkers (e.g., amyloid beta accumulation in the brain detected via positron... (shrink)

The globalization in business and tourism becomes crucial more and more for the economical sustainability of local communities. In the presence of an epidemic outbreak, there must be such a decision on the policy by the host community as whether to accept visitors or not, the number of acceptable visitors, or the condition for acceptable visitors. Making use of an SIRI type of mathematical model, we consider the influence of visitors on the spread of a reinfectious disease in a (...) community, especially assuming that a certain proportion of accepted visitors are immune. The reinfectivity of disease here means that the immunity gained by either vaccination or recovery is imperfect. With the mathematical results obtained by our analysis on the model for such an epidemic dynamics of resident and visitor populations, we find that the acceptance of visitors could have a significant influence on the disease’s endemicity in the community, either suppressive or supportive. (shrink)

BackgroundMore than 15% of Chinese respondents reported somatic symptoms in the last week of January 2020. Promoting resilience is a possible target in crisis intervention that can alleviate somatization.ObjectivesThis study aims to investigate the relationship between resilience and somatization, as well as the underlying possible mediating and moderating mechanism, in a large sample of Chinese participants receiving a crisis intervention during the coronavirus disease 2019 epidemic.MethodsParticipants were invited online to complete demographic information and questionnaires. The Symptom Checklist-90 somatization subscale, (...) 10-item Connor–Davidson resilience scale, and 10-item Perceived Stress Scale were measured.ResultsA total of 2,557 participants were included. Spearman correlation analysis revealed that lower resilience was associated with more somatic symptoms. The conditional process model was proved. The interaction effects between perceived stress and sex predicted somatization.ConclusionResilience is a key predictor of somatization. The mediating effects of perceived stress between resilience and somatization work in the context of sex difference. Sex-specific intervention by enhancing resilience is of implication for alleviating somatization during the coronavirus disease 2019 epidemic. (shrink)

BackgroundSubjective cognitive decline, non-amnestic mild cognitive impairment, and amnestic mild cognitive impairment are regarded to be at high risk of converting to Alzheimer’s disease. Amplitude of low-frequency fluctuations can reflect functional deterioration while diffusion tensor imaging is capable of detecting white matter integrity. Our study aimed to investigate the structural and functional alterations to further reveal convergence and divergence among SCD, naMCI, and aMCI and how these contribute to cognitive deterioration.MethodsWe analyzed ALFF under slow-4 and slow-5 bands and white (...) matter fiber integrity among normal controls, SCD, naMCI, and aMCI groups. Correlation analyses were further utilized among paired DTI alteration, ALFF deterioration, and cognitive decline.ResultsFor ALFF calculation, ascended ALFF values were detected in the lingual gyrus and superior frontal gyrus within SCD and naMCI patients, respectively. Descended ALFF values were presented mainly in the LING, SFG, middle frontal gyrus, and precuneus in aMCI patients compared to CN, SCD, and naMCI groups. For DTI analyses, white matter alterations were detected within the uncinate fasciculus in aMCI patients and within the superior longitudinal fasciculus in naMCI patients. SCD patients presented alterations in both fasciculi. Correlation analyses revealed that the majority of these structural and functional alterations were associated with complicated cognitive decline. Besides, UF alterations were correlated with ALFF deterioration in the SFG within aMCI patients.ConclusionsSCD shares structurally and functionally deteriorative characteristics with aMCI and naMCI, and tends to convert to either of them. Furthermore, abnormalities in white matter fibers may be the structural basis of abnormal brain activation in preclinical AD stages. Combined together, it suggests that structural and functional integration may characterize the preclinical AD progression. (shrink)

Objective: This study aimed to compare the effects of two intervention programs, high-intensity interval training and moderate-intensity training, on anxiety, depression, stress, and resilience during the confinement caused by the coronavirus disease 2019 in healthy adults.Methods: A total of 67 adults who participated were randomly assigned to two groups: HIIT and MIT groups. The MIT group had to perform a home-based intervention based on aerobic exercises, whereas the HIIT group had to perform a home-based intervention based on HIIT exercises. (...) The two groups had to complete the same physical exercise volume, 40 min per session during the confinement period. Depression, anxiety, stress, and resilience were assessed before and after the intervention.Results: Results showed that HIIT and MIT significantly reduced the stress, anxiety, and depression as well as increase the resilience. Moreover, the improvements obtained in the HIIT group seem to be greater than those of the MIT group in depression.Conclusions: HIIT and MIT decreased anxiety, stress, and depression as well as increased resilience during the COVID-19 confinement. In addition, the HIIT intervention seemed to be more beneficial to reduce depression than the MIT intervention. (shrink)

In this paper, we examine the practice and promises of digital phenotyping. We build on work on the ‘data self’ to focus on a medical domain in which the value and nature of knowledge and relations with data have been played out with particular persistence, that of Alzheimer's disease research. Drawing on research with researchers and developers, we consider the intersection of hopes and concerns related to both digital tools and Alzheimer's disease using the metaphor of the ‘data (...) shadow’. We suggest that as a tool for engaging with the nature of the data self, the shadow is usefully able to capture both the dynamic and distorted nature of data representations, and the unease and concern associated with encounters between individuals or groups and data about them. We then consider what the data shadow ‘is’ in relation to ageing data subjects, and the nature of the representation of the individual's cognitive state and dementia risk that is produced by digital tools. Second, we consider what the data shadow ‘does’, through researchers and practitioners’ discussions of digital phenotyping practices in the dementia field as alternately empowering, enabling and threatening. (shrink)

IntroductionCognitive impairment is a highly prevalent non-motor feature of Parkinson’s disease. A better understanding of the underlying pathophysiology may help in identifying therapeutic targets to prevent or treat dementia. This study sought to identify metabolic alterations in the prefrontal cortex, a key region for cognitive functioning that has been implicated in cognitive dysfunction in PD.MethodsProton Magnetic Resonance Spectroscopy was used to investigate metabolic changes in the PFC of a cohort of cognitively normal individuals without PD, as well as PD (...) participants with either normal cognition, mild cognitive impairment, or dementia. Ratios to Creatine resonance were obtained for glutamate, glutamine and glutamate combined, N-acetylaspartate, myoinositol, and total choline, and correlated with cognitive scores across multiple domains administered to the PD participants only.ResultsWhen individuals retain cognitive capabilities, the presence of Parkinson’s disease does not create metabolic disturbances in the PFC. However, when cognitive symptoms are present, PFC Glu/Cre ratios decrease with significant differences between the PD-NC and PPD groups. In addition, Glu/Cre ratios and memory scores were marginally associated, but not after Bonferroni correction.ConclusionThese preliminary findings indicate that fluctuations in prefrontal glutamate may constitute a biomarker for the progression of cognitive impairments in PD. We caution for larger MRS investigations of carefully defined PD groups. (shrink)