In this paper, we examine the case of psychedelic medicine for Alzheimer’s disease and related dementias (AD/ADRD). These “mind-altering” drugs are not currently offered as treatments to persons with AD/ADRD, though there is growing interest in their use to treat underlying causes and associated psychiatric symptoms. We present a research agenda for examining the ethics of psychedelic medicine and research involving persons living with AD/ADRD, and offer preliminary analyses of six ethical issues: the impact of psychedelics on autonomy and (...) consent; the impact of “ego dissolution” on persons experiencing a pathology of self; how psychedelics might impact caregiving; the potential exploitation of patient desperation; institutional review boards’ orientation to psychedelic research; and methods to mitigate inequity. These ethical issues are magnified for AD/ADRD but bear broader relevance to psychedelic medicine and research in other clinical populations. (shrink)

Alzheimer's disease is the most common neurodegenerative disorder in today's developed world that is also increasingly picked out as a focal theme in fictional literature. In dealing with the subjectivity of human experience, such literature enhances the reader's empathy and is able to teach about moral, emotional and philosophical issues, offering the chance to see situations from a position otherwise possibly never taken by the reader. The understanding and insight so gained may well be unscientific, but the literary approach (...) offers an insight into the whole person's perspective and the particularity and uniqueness of a situation that includes ethical conflicts. A key motif of fictional literature centred around dementia remains the burden the adult-child carer is confronted with, considering the parent's remorseless decline and personality change, the sudden demand for devoted and continuous care, and the constantly changing relationship with the declining parent. In the context of an ever increasing demand for a constructive public discussion regarding end-of-life treatment of demented patients, Christine Devars (Le Piano Désaccordé) and Andrés Barba (Ahora Tocad Música de Baile) illustrate how powerful and burdensome the impact of Alzheimer's disease is on both patient and carer and what extremes may be reached under such truly exceptional circumstances. (shrink)

During the cold war, Frank Fenner and Francis Ratcliffe studied mathematically the coevolution of host resistance and parasite virulence when myxomatosis was unleashed on Australia’s rabbit population. Later, Robert May called Fenner the “real hero” of disease ecology for his mathematical modeling of the epidemic. While Ratcliffe came from a tradition of animal ecology, Fenner developed an ecological orientation in World War II through his work on malaria control —that is, through studies of tropical medicine. This makes Fenner at (...) least a partial exception to other senior disease ecologists in the region, most of whom learned their ecology from examining responses to agricultural challenges and animal husbandry problems in settler colonial society. Here I consider the local ecologies of knowledge in southeastern Australia during this period, and describe the particular cold-war intellectual niche that Fenner and Ratcliffe inhabited. (shrink)

Analyses of biological concepts of disease and social conceptions of health indicate that they are structurally interdependent. This in turn suggests the need for a bridge theory of illness. The main features of such a theory are an emphasis on the logical properties of value terms, close attention to the features of the experience of illness, and an analysis of this experience as action failure, drawing directly on the internal structure of action. The practical applications of this theory are (...) outlined for a number of problems in each of the three main practical areas, clinical work, teaching and research. In each case the resources of the theory suggest new models and generate new results. The full practical significance of the theory, however, is shown to consist in the way in which it ties together biological and social theories into an integrated picture of the conceptual structure of medicine as a whole. It is argued, finally, that practical efficiency of this kind is a test of theory not only in the philosophy of medicine but also in general philosophy. (shrink)

This article uses Marc Lewis’ work as a springboard to discuss the socio-political context of the brain disease model of addiction (BDMA). The claim that promotion of the BDMA is the only way the general public can be persuaded to withhold blame and punishment from addicts is critically examined. After a discussion of public understandings of the disease concept of addiction, it is pointed out that it is possible to develop a scientific account of addiction which is neither (...) a disease nor a moral model but which the public could understand. Evidence is reviewed to suggest that public acceptance of the disease concept is largely lip-service and that the claim the BDMA removes stigma among the public and professionals is unsupported by evidence. Further, there is good evidence that biogenetic explanations of mental/behavioural disorders in general have been counterproductive in the attempt to ally stigma. A model of addiction as a disorder of choice may attract special problems in public-facing communications and risks being misunderstood. However, ways of presenting this model to the public are suggested that may avoid such risks. Lastly, the claim that the BDMA is the only way of ensuring access to treatment and of maintaining research funding for addiction is disputed and a way in which these benefits can be retained under a disorder-of-choice model proposed. The article concludes by enthusiastically endorsing Lewis’ call for a third stage in the governing image of addiction. (shrink)

The claim that addiction is a brain disease is almost universally accepted among scientists who work on addiction. The claim’s attraction rests on two grounds: the fact that addiction seems to be characterized by dysfunction in specific neural pathways and the fact that the claim seems to the compassionate response to people who are suffering. I argue that neural dysfunction is not sufficient for disease: something is a brain disease only when neural dysfunction is sufficient for impairment. (...) I claim that the neural dysfunction that is characteristic of addiction is not sufficient for impairment, because people who suffer from that dysfunction are impaired, sufficiently to count as diseased, only given certain features of their context. Hence addiction is not a brain disease (though it is often a disease, and it may always involve brain dysfunction). I argue that accepting that addiction is not a brain disease does not entail a moralizing attitude toward people who suffer as a result of addiction; if anything, it allows for a more compassionate, and more effective, response to addiction. (shrink)

Many existing biomedical vocabulary standards rest on incomplete, inconsistent or confused accounts of basic terms pertaining to diseases, diagnoses, and clinical phenotypes. Here we outline what we believe to be a logically and biologically coherent framework for the representation of such entities and of the relations between them. We defend a view of disease as involving in every case some physical basis within the organism that bears a disposition toward the execution of pathological processes. We present our view in (...) the form of a list of terms and definitions designed to provide a consistent starting point for the representation of both disease and diagnosis in information systems in the future. (shrink)

Transient receptor potential vanilloid 4 (TRPV4), a member of the TRP superfamily, is a broadly expressed, cell surface‐localized cation channel that is activated by a variety of environmental stimuli. Importantly, TRPV4 has been increasingly implicated in the regulation of cellular morphology. Here we propose that TRPV4 and the cytoskeletal remodeling small GTPase RhoA together constitute an environmentally sensitive signaling complex that contributes to pathological cell cytoskeletal alterations during neurological injury and disease. Supporting this hypothesis is our recent work demonstrating (...) direct physical and bidirectional functional interactions of TRPV4 with RhoA, which can lead to activation of RhoA and reorganization of the actin cytoskeleton. Furthermore, a confluence of evidence implicates TRPV4 and/or RhoA in pathological responses triggered by a range of acute neurological insults ranging from stroke to traumatic injury. While initiated by a variety of insults, TRPV4–RhoA signaling may represent a common pathway that disrupts axonal regeneration and blood–brain barrier integrity. These insights also suggest that TRPV4 inhibition may represent a safe, feasible, and precise therapeutic strategy for limiting pathological TRPV4–RhoA activation in a range of neurological diseases. (shrink)

Extrapolation from a well-understood base population to a less-understood target population can fail if the base and target populations are not sufficiently similar. Differences between laboratory mice and humans, for example, can hinder extrapolation in medical research. Mice that carry a partial or complete human physiological system, known as humanized mice, are supposed to make extrapolation more reliable by simulating a variety of human diseases. But what justifies our belief that these mice are similar enough to their human counterparts to (...) simulate human disease? I argue that, unless three requirements are met in the process of humanizing mice, very little does. My requirements are not meant to provide necessary and sufficient conditions that guarantee a particular outcome. Instead, they serve as a heuristic for guiding scientific judgments involving extrapolation. In developing each requirement, I engage with philosophical issues concerning the nature of model-based science and the mechanistic approach (and its limits) to making generalizations in the life sciences. (shrink)

Presymptomatic testing for Huntington's disease has given rise to several ethical problems relating to such issues as confidentiality, the privacy of the individual, the testing of minors and informed consent in connection with blood sample donation. A multidisciplinary conference of staff from genetic centres involved with presymptomatic testing was organised in Cardiff to discuss these and other problems. Recommendations on good practice are described under four headings: pre- and post-test counselling; confidentiality in relation to test results; collection and storage (...) of DNA, and criteria for testing. (shrink)

The traditional contrast between naturalist and normativist disease concepts fails to capture the most salient features of the health concepts debate. By using health concepts as a window on background notions of medical science and ethics, I show how Christopher Boorse (an influential naturalist) and Lennart Nordenfelt (an influential normativist) actually share deep assumptions about the character of medicine. Their disease concepts attempt, in different ways, to shore up the same medical model. For both, health concepts function like (...) demarcation criteria in the philosophy of science: they mark off the jurisdiction of medical science, and protect it from an inappropriate intrusion of socioeconomic factors, which threaten the integrity of modern medicine. These views are challenged by new developments in healthcare such as managed care and total quality review. To frame the health concepts debate in a way that better captures the issues integral to these new developments, I advance a new way of reading the distinction between weak and strong normativists. Strong normativists are skeptical of the demarcation project, think facts and values cannot be disentangled, and hold that socioeconomic conditions unavoidably influence how pathology is understood. The new health concepts debate should be framed as one between weak and strong normativists, and it concerns how we should respond to the current developments in health care. (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)

This article aims at answering the following questions: What is the influence of age structure on the spread of coronavirus disease 2019? What can be the impact of stringency policy on the spread of COVID-19? What might be the quantitative effect of development levelincome and number of hospital beds on the number of deaths due to the COVID-19 epidemic? By employing the methodologies of generalized linear model, generalized moments method, and quantile regression models, this article reveals that the shares (...) of median age, age 65, and age 70 and older population have significant positive impacts on the spread of COVID-19 and that the share of age 70 and older people in the population has a relatively greater influence on the spread of the pandemic. The second output of this research is the significant impact of stringency policy on diminishing COVID-19 total cases. The third finding of this paper reveals that the number of hospital beds appears to be vital in reducing the total number of COVID-19 deaths, while GDP per capita does not affect much the level of deaths of the COVID-19 pandemic. Finally, this article suggests some governmental health policies to control and decrease the spread of COVID-19. (shrink)

I argue that ductal carcinoma in situ (DCIS), the tumor most commonly diagnosed by breast mammography, cannot be confidently classified as cancer, that is, as pathological. This is because there may not be dysfunction present in DCIS—as I argue based on its high prevalence and the small amount of risk it conveys—and thus DCIS may not count as a disease by dysfunction-requiring approaches, such as Boorse’s biostatistical theory and Wakefield’s harmful dysfunction account. Patients should decide about treatment for DCIS (...) based on the risks it poses and the risks and benefits of treatment, not on its disease status. (shrink)

BackgroundPublic health guidelines have recommended that elective medical procedures, including deep brain stimulation surgery for Parkinson’s disease, should not be scheduled during the coronavirus pandemic to prevent further virus spread and overload on health care systems. However, delaying DBS surgery for PD may not be in the best interest of individual patients and is not called for in regions where virus spread is under control and inpatient facilities are not overloaded.MethodsWe administered a newly developed phone questionnaire to 20 consecutive (...) patients with PD who received DBS surgery in Ruijin Hospital in Shanghai during the COVID-19 pandemic. The questionnaire was designed to gather the patients’ experiences and perceptions on the impact of COVID-19 on their everyday activities and access to medical care.ResultsMost of the patients felt confident about the preventive measures taken by the government and hospitals, and they have changed their daily living activities accordingly. Moreover, a large majority of patients felt confident obtaining access to regular and COVID-19-related health care services if needed. Routine clinical referral, sense of security in the hospital during the outbreak, and poor control of PD symptoms were the three main reasons given by patients for seeking DBS surgery during the COVID-19 pandemic.ConclusionThe COVID-19 pandemic has considerably impacted medical care and patients’ lives but elective procedures, such as DBS surgery for PD, do not need to be rescheduled when the health care system is not overloaded and adequate public health regulations are in place. (shrink)

An increasing number of older patients have to decide on a treatment plan for advanced chronic kidney disease, involving dialysis or conservative care. Shared decision-making is recommended as the model for decision-making in such preference-sensitive decisions. The aim of SDM is to come to decisions that are consistent with the patient’s values and preferences and made by the patient and healthcare professional working together. In clinical practice, however, SDM appears to be not yet routine and needs further implementation. A (...) shift from a biomedical to a person-centered conception might help to make the process more shared. Shared should, therefore, be interpreted as two persons bringing two perspectives to the table, that both need to be explored during the decision-making process. Starting from the patient’s perspective will enable to determine the mutual goals of care first and, subsequently, determine the best way for achieving those goals. To perform such SDM, the healthcare professional needs to become a skilled companion, being part of the patient’s relational context, and start asking the right questions about what matters to the patient as person. In this article, we describe the need for a person-centered conception of SDM for the setting of older patients with advanced CKD. (shrink)

Background Between 2013 and 2016, West Africa experienced the largest ever outbreak of Ebola Virus Disease. In the absence of registered treatments or vaccines to control this lethal disease, the World Health Organization coordinated and supported research to expedite identification of interventions that could control the outbreak and improve future control efforts. Consequently, the World Health Organization Research Ethics Review Committee was heavily involved in reviews and ethics discussions. It reviewed 24 new and 22 amended protocols for research (...) studies including interventional and observational studies. WHO-ERC reviews WHO-ERC provided the reviews within on average 6 working days. The WHO-ERC often could not provide immediate approval of protocols for reasons which were not Ebola Virus Disease specific but related to protocol inconsistencies, missing information and complex informed consents. WHO-ERC considerations on Ebola Virus Disease specific issues are presented. Conclusions To accelerate study approval in future public health emergencies, we recommend: internally consistent and complete submissions with information documents in language participants are likely to understand, close collaboration between local and international researchers from research inception, generation of template agreements for data and sample sharing and use during the ongoing global consultations on bio-banks, formation of Joint Scientific Advisory and Data Safety Review Committees for all studies linked to a particular intervention or group of interventions, formation of a Joint Ethics Review Committee with representatives of the Ethics Committees of all institutions and countries involved to strengthen reviews through the different perspectives provided without the ‘opportunity costs’ for time to final approval of multiple, independent reviews, direct information exchange between the chairs of advisory, safety review and ethics committees, more Ethics Committee support for investigators than is standard and a global consultation on criteria for inclusion of pregnant women and children in interventional studies for conditions which put them at particularly high risk of mortality or other irreversible adverse outcomes under standard-of-care. (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)

Laws and policies are vital tools in preventing outbreaks and limiting the further spread of disease, but they can vary in content and implementation. This manuscript provides insight into challenges in responding to recent vaccine-preventable disease outbreaks by examining legislative changes in California, policy changes on certain university campuses, and the laws implicated in a measles outbreak in Minnesota.

Patients with advanced Alzheimer's disease experience cognitive impairment and physical disabilities in daily life. Currently, there are no treatments available to slow down the course of the disease, and limited treatments exist only to treat symptoms. However, deep brain stimulation of the nucleus basalis of Meynert has been reported to improve cognitive function in individuals with AD. Here, we report the effects of NBM-DBS on cognitive function in a subject with severe AD. An 80-year-old male with severe AD (...) underwent surgery for bilateral NBM-DBS electrode placement. After 10 weeks of stimulation, Mini-Mental State Examination assessment improved from a score of 5 to 9 points, and assessment using the Alzheimer's Disease Assessment Scale–Cognitive Subscale showed a marked reduction in total score from 43 to 33 points, suggesting cognitive benefits from NBM-DBS. The patient's postoperative course was complicated by a subdural effusion that occurred several days after surgery, with complete recovery. Interestingly, the subject also displayed abnormal thermoregulation with stimulation initiation and stimulation parameter modifications. NBM-DBS may serve as a potential therapy for severe AD patients.Clinical Trial Registration: ChiCTR1900022324. (shrink)

This study examines how low-income African American mothers of children with sickle cell disease cope with the reproductive implications of having passed a genetic disease on to their children. Based on in-depth interviews with 29 African American mothers, I found that most mothers knew about SCD prior to having a child with the disease; many knew they were carriers of the sickle cell trait. In explaining why this knowledge did not lead them to alter their reproductive behaviors, (...) mothers invoked a theme of medical mismanagement; that is, they said the genetic screening programs for SCD did not provide them with enough medical knowledge about the disease. The implication that adequate knowledge about SCD would have affected their childbearing choices, however, is contradicted by their subsequent reproductive behaviors. I argue that the SCD diagnosis threatened motherhood, an important cultural value among low-income African American women, and that they protected their reproductive autonomy by obfuscating SCD medical knowledge. (shrink)

While philosophical questions about health and disease have attracted much attention in recent decades, and while opinions are divided on most issues, influential accounts seem to embrace negativism about health, according to which health is the absence of disease. Some subscribe to unrestricted negativism, which claims that negativism applies not only to the concepts of health and disease as used by healthcare professionals but also to the lay concept that underpins everyday thinking. Whether people conceptualize health in (...) this manner has implications for medical care and public health, and so we set out to examine this claim in two studies. Participants were asked to assess and compare the health states of two people presented in two vignettes. We found that both lay people and medical students conceptualize health as something more than the absence of disease. We argue that our findings highlight a need to rethink unrestricted negativism and indicate a need to rethink the way the debate has traditionally focused on disease. (shrink)

Intensive research is carried out to develop a disease-modifying drug for Alzheimer’s disease. The development of drug candidates that reduce Aß or tau in the brain seems particularly promising. However, these drugs target people at risk for AD, who must be identified before they have any, or only moderate, symptoms associated with the disease. There are different strategies that may be used to identify these individuals. Each of these strategies raises different ethical challenges. In this paper, we (...) analyse these challenges in relation to the risk stratification for AD necessary for using these drugs. We conclude that the new drugs must generate large health benefits for people at risk of developing AD to justify the ethical costs associated with current risk stratification methods, benefits much larger than current drug candidates have. This conclusion raises a new set of ethical questions that should be further discussed. No data are available. (shrink)

Resumen En el presente trabajo se investigan los alcances y las consecuencias que se desprenden de utilizar a Heidegger en el campo de la filosofía de la medicina. Con este fin, la investigación se divide en los siguientes puntos: 1) se explicitará en qué puede consistir una “antropologización” del pensamiento heideggeriano; 2) se ofrecerá una descripción general respecto de las teorías de la salud y enfermedad más significativas y actuales en el campo de la teoría de la medicina; 3) nos (...) detendremos en el análisis relacionado con el problema de la enfermedad desde una perspectiva heideggeriana, para finalmente, 4) ofrecer algunas reflexiones críticas en relación con el análisis ofrecido.In this contribution we investigate the scope and consequences that arise from applying Heidegger in the field of philosophy of medicine. For this purpose, the paper is divided in the following points: First, we will make explicit the meaning of an “anthropologization” of Heidegger's thought. Second, an overview of the most significant contemporary theories of health and disease in the field of theory of medicine will be offered. Third, we will interpret the meaning of disease from a Heideggerian perspective. Finally, 4) we will offer some critical reflections offered in relation to the analysis. (shrink)

Johnson and Stricker published an opinion piece in the Journal of Medical Ethics presenting their perspective on the 2008 agreement between the Infectious Diseases Society of America (IDSA) and the Connecticut Attorney General with regard to the 2006 IDSA treatment guideline for Lyme disease. Their writings indicate that these authors hold unconventional views of a relatively common tick-transmitted bacterial infection caused by the spirochete Borrelia burgdorferi. Therefore, it should come as no surprise that their opinions would clash with the (...) IDSA's evidence-based guidelines for the diagnosis and treatment of Lyme disease. Their allegations of conflict of interest against the IDSA resemble those made against the National Institutes of Health, the Food and Drug Administration and the Centers for Disease Control and Prevention in 2000, which were found to be baseless. It is the responsibility of all physicians and medical scientists to stand up to antiscientific, baseless and unethical attacks on those who support an evidence-based approach to caring for patients. (shrink)

Norman Daniels argues that health is important for justice because it affects the distribution of opportunities. He claims that a just society should guarantee fair opportunities by promoting and restoring the “normal functioning” of its citizens, that is, their health. The scope of citizens' mutual obligations with respect to health is defined by a reasonable agreement that, according to Daniels, should be based on the distinction between normal functioning and pathology drawn by the biomedical sciences. This paper deals with the (...) question whether it is legitimate to ascribe the responsibility of defining this important moral boundary to the biomedical sciences, which Daniels regards as value neutral. Daniels appeals to Christopher Boorse's sophisticated bio-statistical theory (BST) to show the plausibility of a value-neutral distinction between normal functioning and pathology. Here I argue that a careful analysis of the concept of normal functioning, such as the one offered by the recent critique by Elselijn Kingma, shows that it depends from evaluative assumptions. This, I argue, implies that Daniels's theory must give up its naturalistic commitments. In the conclusion, the paper offers a detailed discussion and an objection to one of Daniels's arguments in favor of a moderate form of normativism that remains too close to Boorse's naturalism. (shrink)

In a previous paper the concept of disease was fuzzy-logically analyzed and a sketch was given of a prototype resemblance theory of disease (Sadegh-Zadeh (2000). J. Med. Philos., 25:605–38). This theory is outlined in the present paper. It demonstrates what it means to say that the concept of disease is a nonclassical one and, therefore, not amenable to traditional methods of inquiry. The theory undertakes a reconstruction of disease as a category that in contradistinction to traditional (...) views is not based on a set of common features of its members, that is individual diseases, but on a few best examples of the category, called its prototypes, and a similarity relationship such that a human condition is considered a disease if it resembles a prototype. It enables new approaches to resolving many of the stubborn problems associated with the concept of disease. (shrink)

Alzheimer’s disease is emerging into public view in unprecedented ways. Foremost among these is the embodied form of elderly men and women appearing in commercial imagery for patient advocacy groups or pharmaceutical advertisements, but scientific imagery also seeps into the visual media cultures that surround us. The recent reconfiguration of Alzheimer’s disease is due to expanding ageing populations, an aggressive biopharmaceutical industry becoming a fast-growing material-semiotic realm that is providing powerful images of both gendered and racialized embodiment. Such (...) a visual, and yet highly material, realm is in need of feminist interventions, engaging with the images and ideas that circulate around ageing, medicine, human and non-human embodiment. From a non-representationalist and posthumanist perspective identified as feminist visual studies of technoscience, the authors seek to further the discussion in the direction of understanding the ‘scattered ontologies’ of Alzheimer’s — in laboratory practice, the realm of medical media and in commercial appeals to coherent individuality and human cognition — as gendered domains of figural reality and performative matter. (shrink)

Given the past two decades of over 40 failed trials of amyloid-lowering therapies in Alzheimer’s Disease (AD), many of which succeeded in lowering amyloid as designed, we present an ethical argument for emptying the drug pipeline of tests of amyloid-lowering agents so as to end the historical dominance of the amyloid-reducing therapeutic approach in AD.

The fact that the emergence of “technoscience,” resulting from the coalescing of science and technology, may have serious social and cultural impact has been debated in recent years particularly with regard to the field of medicine. The present article is exploring the scope and limits of the “technoscientization” of medicine using the example of rare disease patient associations. It is investigated whether and to what extent these organizations adopt technoscientific illness identities and subscribe to the research priorities and objectives (...) of biomedicine. In addition, it is analyzed whether Paul Rabinow’s highly influential concept of biosociality entails a technoscientific model of identity or, quite to the contrary, offers a framework for contesting biomedical ascriptions of identities. As the article shows, patient associations do refer to technoscientific definitions of diseases yet constantly modify and transform them based on their everyday illness experiences. Likewise, the “biosociality” of rare disease patients emerges from the shared experience of having been neglected by mainstream medical research rather than from supposedly objective biomedical classifications. (shrink)

Deletions, duplications, insertions, inversions, and translocations, collectively called structural variations (SVs), affect more base pairs of the genome than any other sequence variant. The recent technological advancements in genome sequencing have enabled the discovery of tens of thousands of SVs per human genome. These SVs primarily affect non‐coding DNA sequences, but the difficulties in interpreting their impact limit our understanding of human disease etiology. The functional annotation of non‐coding DNA sequences and methodologies to characterize their three‐dimensional (3D) organization in (...) the nucleus have greatly expanded our understanding of the basic mechanisms underlying gene regulation, thereby improving the interpretation of SVs for their pathogenic impact. Here, we discuss the various mechanisms by which SVs can result in altered gene regulation and how these mechanisms can result in rare genetic disorders. Beyond changing gene expression, SVs can produce novel gene‐intergenic fusion transcripts at the SV breakpoints. (shrink)

American Trypanosomiasis, known as Chagas disease, was discovered in 1909 under peculiar circumstances: its discoverer, Carlos Chagas, was sent to a small village of Central Brazil to carry out an anti-malaria campaign when he came across a blood sucking insect—the vector for the parasite infection. He had been alerted to the coincidence of peculiar symptoms and the presence of this insect in the wood and earth dwellings of the region. He was deeply involved in theoretical controversies in international protozoology; (...) he was engaged in the consolidation of a scientific role and corresponding institutional conditions in Brazil, and equally immersed in the nationalist sanitary struggles of his days. In these contexts, Chagas assembled a remarkable discovery discourse, regarding the biology of the parasite, its life cycle and mode of transmission. Furthermore, he provided the clinical description of a new disease. Despite immediate international recognition, however, the unstable institutional arrangements surrounding his work damaged its local legitimacy for decades. His authority was widely recognized abroad, but rejected at home. (shrink)

THIS PAPER IS A COMMENTARY ON LUDWIK FLECK'S ESSAY ON THE CONNECTION BETWEEN WHAT HE CALLS "THOUGHT-STYLES" AND SCIENTIFIC AND MEDICAL CONCEPTS. THE IDEA OF A "THOUGHT-STYLE" APPLIED TO CONCEPTS OF DISEASE IS THAT THEY ARE NOT ONLY VALUE-LADEN IN THE SENSE OF INCLUDING NORMATIVE DIMENSIONS. THEY ALSO EMBRACE BROAD SOCIAL FACTORS, AS WELL. I ARGUE THAT THOUGHT-STYLES SHOULD BE UNDERSTOOD TO BE "OPEN-TEXTURED," ADMITTING A PLURALITY OF VALUE CONSIDERATIONS TO CONCEPTS OF DISEASE.

Automated decision-making (ADM) systems can be worn in and on the body for various purposes, such as for tracking and managing chronic conditions. One case in point is do-it-yourself open-source artificial pancreas systems, through which users engage in what is referred to as “looping”; combining continuous glucose monitors and insulin pumps placed on the body with digital communication technologies to develop an ADM system for personal diabetes management. The idea behind these personalized systems is to delegate decision-making regarding insulin to (...) an algorithm that can make autonomous decisions. Based on interviews and photo diaries with Danish “loopers”, this paper highlights two interrelated narratives of how users have to care for the loop by _maintaining_ a stable communication circuit between body and ADM system, and by _modifying_ the loop through analysis and reflection. It shows how the human takes turns with the ADM system through practical doings and anticipation to safeguard continuous management of chronic disease. (shrink)

The classification of ageing as a disease is fundamental to developing new pharmacological strategies that can target said phenomenon. The European Medicines Agency does not do this and maintains a questionable perspective based on the traditional naturalistic argument and the value-free ideal. An alternative is proposed which, inspired by consequentialism, is committed to considering ageing as a disease in European regulatory contexts as long as the ethical consequences are desirable. Within a realistic framework, I show that making this (...) decision would have moderate positive effects such as increased knowledge about antiageing pharmacology or potential greater chances of completing vital projects. Furthermore, we will see that the main arguments used by critics to show that the negative effects outweigh the positive ones are not sound. Therefore, I conclude that it would be beneficial for the European Medicines Agency to change its position on ageing. (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)

Activity-dependent neuroprotective protein, discovered in our laboratory in 1999, has been characterized as a master gene vital for mammalian brain formation. ADNP de novo mutations in humans result in a syndromic form of autism-like spectrum disorder, including cognitive and motor deficits, the ADNP syndrome. One of the most important cellular processes associated with ADNP is the autophagy pathway, recently discovered by us as a key player in the pathophysiology of schizophrenia. In this regard, given the link between the microtubule and (...) autophagy systems, the ADNP microtubule end binding protein motif, namely, the neuroprotective NAP, was found to enhance autophagy while protecting microtubules and augmenting ADNP's association with both systems. Thus, linking autophagy and ADNP is proposed as a major target for intervention in brain diseases from autism to Alzheimer's disease and our findings introduce autophagy as a possible novel target for treating schizophrenia. Activity-dependent neuroprotective protein binds to microtubule-associated protein light chain 3, which forms the membrane of the autophagosome, a key organelle in the autophagy process and regulates beclin1 formation, an inducer of autophagy. Autophagy plays a major role in Alzheimer's disease and as recently discovered in schizophrenia and autism. (shrink)

Postural instability marks a prevalent symptom of Parkinson’s disease. It often manifests in increased body sway, which is commonly assessed by tracking the Center of Pressure. Yet, in terms of postural control, the body’s Center of Mass, and not CoP is what is regulated in a gravitational field. The aim of this study was to explore the effect of early- to mid-stage PD on these measures of postural control in response to unpredictable visual perturbations. We investigated three cohorts: 18 (...) patients with early to mid-stage PD [Hoehn & Yahr stage ; 1.94 ± 0.70]; a group of 15 age-matched controls ; and a group of 12 young healthy adults. Participants stood on a force plate to track their CoP, while the movement of their entire body was recorded with a video-based motion tracking system to monitor their CoM. A moving room paradigm was applied through a head-mounted virtual reality headset. The stimulus consisted of a virtual tunnel that stretched in the anterior-posterior direction which either remained static or moved back and forth in an unpredictable fashion.We found differences in mean sway amplitude and mean velocities of CoP and CoM between the groups under both conditions, with higher MSA of CoP and CoM for PD and higher mean velocities of both variables for PD and ECT when compared with YCT. Visual perturbation increased mean CoP velocity in all groups but did not have effects on mean CoM velocity or MSA. While being significantly lower for the young adults, the net effect of visual perturbation on mean CoP velocity was similar between patients with PD and age-matched controls. There was no effect of the visual perturbation on mean CoM velocity for any of the groups.Our simultaneous assessment of CoP and CoM revealed that postural control is reflected differently in CoM and CoP. As the motion of CoM remained mostly unaffected, all groups successfully counteracted the perturbation and maintained their balance. Higher CoP velocity for PD and ECT revealed increased corrective motion needed to achieve this, which however was similar in both groups. Thus, our results suggest increased effort, expressed in CoP velocity, to be an effect of age rather than disease in earlier stages of PD. (shrink)

In Japan, most residents with Hansen’s disease live in dedicated sanatoria because of an established quarantine policy, even after being cured of the primary disease. They suffer from secondary diseases and are advancing in age, and advance care planning is increasingly crucial for them to live their lives with dignity in a sanatorium. In this study, we have three aims: to understand how to promote communication about their wishes for medical treatment, care, and recuperation; to identify required assistance; (...) and to explore how to promote ACP in a sanatorium. This study is a qualitative research conducted through semi-structured interviews. The study included 57 ex-Hansen’s disease patients and 66 staff from 10 facilities. Ex-Hansen’s disease patients were expected to consider ACP, but this was in the context of uncertainty about whether a sanatorium would close and whether there would be doctors to manage their needs. They reported being confused when staff rushed to confirm their advance directives, feeling that they were not provided with enough information before being approached. Barriers to promoting ACP were found to be insufficient of team-based care and information sharing, ex-Hansen’s disease patients’ weak interest in their end of life, and their conservative thoughts. We believe that ACP can be achieved by listening to the wishes of recovered patients through regular home care visits by nurses and everyday support by care workers. Furthermore, multidisciplinary coordination is urgently needed for promoting ACP. (shrink)