NPC1 plays a central role in cholesterol egress from endolysosomes, a critical step for maintaining intracellular cholesterol homeostasis. Despite recent advances in the field, the full repertoire of molecules and pathways involved in this process remains unknown. Emerging evidence suggests the existence of NPC1‐independent, alternative routes. These may involve vesicular and non‐vesicular mechanisms, as well as release of extracellular vesicles. Understanding the underlying molecular mechanisms that bypass NPC1 function could have important implications for the development of therapies for (...) lysosomal storage disorders. Here we discuss how cholesterol may be exported from lysosomes in which NPC1 function is impaired. (shrink)

The first and rate‐limiting step of steroidogenesis is the transfer of cholesterol from the outer mitochondrial membrane to the inner membrane where it is converted to pregnenolone by cytochrome P450 side‐chain cleavage (P450scc). This reaction is modulated in the gonads and adrenals by the steroidogenic acute regulatory protein (StAR), however, the mechanism used by StAR is not understood. The outer and inner mitochondrial membranes are joined at contact sites that are thought to be held in place by protein complexes (...) that bridge the two membranes. While it is generally accepted that proteins are imported into the mitochondrion via contact sites, it is not clear whether cholesterol takes the same conduit to the inner membrane. Strategies to combat diseases caused by interrupted cholesterol transfer will rely on a full understanding of the steroidogenic mechanism. The challenge for the future is to determine whether StAR relies on the molecular architecture that spans the mitochondrial intermembrane space to deliver its cargo. BioEssays 25:252–258, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The concentration of low‐density lipoprotein (LDL) cholesterol (C) in plasma is a key determinant of cardiovascular disease risk and human genetic studies have long endeavoured to elucidate the pathways that regulate LDL metabolism. Massive genome‐wide association studies (GWASs) of common genetic variation associated with LDL‐C in the population have implicated SORT1 in LDL metabolism. Using experimental paradigms and standards appropriate for understanding the mechanisms by which common variants alter phenotypic expression, three recent publications have presented divergent and even contradictory (...) findings. Interestingly, although these reports each linked SORT1 to LDL metabolism, they did not agree on a mechanism to explain the association. Here, we review recent mechanistic studies of SORT1 – the first gene identified by GWAS as a determinant of plasma LDL‐C to be evaluated mechanistically. (shrink)

The close link between signaling by the developmental regulators of the Hedgehog family and cholesterol biochemistry has been known for some time. The morphogen is covalently attached to cholesterol in a peculiar autocatalytic reaction and embryonal disruption of cholesterol synthesis leads to malformations that mimic Hh signaling defects. Recently, it was furthermore shown that secreted Hh could hitchhike on lipoprotein particles to establish its morphogenic gradient in the developing embryo. Additionally, there is new evidence that the Hh‐receptor (...) Patched transmits the Hh signal by modulating the secretion of an inhibitory sterol molecule from the receiving cells. Here we present some of the most recent discoveries on the Hh–sterol link and discuss their implications from a systems design perspective. We predict that a robust functioning of the Hh pathway will require the involvement of more sterol metabolites, and these should be the subject of future research. BioEssays 29:1085–1094, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Brain function depends on the cooperation between highly specialized cells. Neurons generate electrical signals and glial cells provide structural and metabolic support. Here, I propose a new kind of job‐sharing between neurons and astrocytes. Recent studies on primary cultures of highly purified neurons from the rodent central nervous system (CNS) suggest that, during development, neurons reduce or even abandon cholesterol synthesis to save energy and import cholesterol from astrocytes via lipoproteins. The cholesterol shuttle may be restricted to (...) compartments distant from the soma including synapses and may be regulated by electrical activity. Testing these hypotheses will help to improve our still insufficient understanding of brain cholesterol metabolism and its role in neurodegeneration. BioEssays 25:72–78, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

Interleukin‐1 receptor‐associated kinase‐1 (IRAK1) is linked to the pathogenesis of atherosclerosis; however, its role in macrophage foam cell formation is not known. Therefore, the present study investigated the role of IRAK1 in lipid uptake, biosynthesis, and efflux in THP‐1 derived macrophages and human monocyte‐derived macrophages (HMDMs). Ox‐LDL (40 μg/mL, 15 minutes–48 hours) treatment induced time‐dependent increase in IRAK1, IRAK4, and Stat1 activation in THP‐1 derived macrophages. IRAK1/4 inhibitor (INH) or IRAK1 siRNA significantly attenuated cholesterol accumulation, DiI‐Ox‐LDL binding, and uptake (...) while cholesterol efflux to apoAI and HDL was enhanced in THP‐1 derived macrophages and HMDMs. Ox‐LDL treatment significantly increased the mRNA expression of CD36, LOX‐1, SR‐A, ABCA1, ABCG1, Caveolin‐1, CYP27A1 while that of SR‐BI was decreased. IRAK1/4 inhibition or IRAK1 knockdown, however, attenuated Ox‐LDL‐induced CD36 expression; augmented ABCA1 and ABCG1 expression while expression of others was unaffected in THP‐1 derived macrophages and HMDMs. Moreover, IRAK1/4 inhibition had no significant effect on genes involved in lipid biosynthesis. In IRAK1/4 INH pre‐treated THP‐1 derived macrophages Ox‐LDL‐induced Stat1 phosphorylation and its binding to CD36 promoter was significantly attenuated while LXRα expression and its binding to the ABCA1/ABCG1 locus, NFATc2 activation and its binding to ABCA1 locus was enhanced. The present study thus demonstrates that IRAK regulates lipid accumulation by modulating CD36‐mediated uptake and ABCA1‐, ABCG1‐dependent cholesterol efflux. Therefore, IRAK1 can be a potential target for preventing macrophage foam cell formation. (shrink)

Two posttranslational lipid modifications present on all Hedgehog (Hh) morphogens—an N‐terminal palmitate and a C‐terminal cholesterol—are established and essential regulators of Hh biofunction. Yet, for several decades, the question of exactly how both lipids contribute to Hh signaling remained obscure. Recently, cryogenic electron microscopy revealed different modes by which one or both lipids may contribute directly to Hh binding and signaling to its receptor Patched1 (Ptc). Some of these modes demand that the established release factor Dispatched1 (Disp) extracts dual‐lipidated (...) Hh from the cell surface, and that another known upstream signaling modulator called Scube2 chaperones the dual‐lipidated morphogen to Ptc. By mechanistically and biochemically aligning this concept with established in vivo and recent in vitro findings, this reflection identifies remaining questions in lipidated Hh transport and evaluates additional mechanisms of Disp‐ and Scube2‐regulated release of a second bioactive Hh fraction that has one or both lipids removed. (shrink)

You are what you eat – this well‐known phrase properly describes the phenomenon of the effects of diet on acute and chronic inflammation. Several lipids and lipophilic compounds that are delivered with food or are produced in situ in pathological conditions exert immunomodulatory activity due to their interactions with the plasma membrane. This group of compounds includes cholesterol and its oxidized derivatives, fatty acids, α‐tocopherol, and polyphenols. Despite their structural heterogeneity, all these compounds ultimately induce changes in plasma membrane (...) architecture and fluidity. By doing this, they modulate the dynamics of plasma membrane receptors, such as TLR4. This receptor is activated by lipopolysaccharide, triggering acute inflammation during bacterial infection, which often leads to sepsis and is linked with diverse chronic inflammatory diseases. In this review, we discuss how the impact on plasma membrane properties contributes to the immunomodulatory activity of dietary compounds, pointing to the therapeutic potential of some of them.Also watch the Video Abstract. (shrink)

In this paper, I sound a warning note about the medicalization of risk conditions such as high cholesterol, especially in a health care climate of resource scarcity.

Despite recent advances in the research related to air pollution and associated adverse cardiovascular events, the combined effects of air pollution, climate change, and SARS‐CoV‐2 infection on cardiovascular health need to be researched further. This Commentary addresses their impacts on cardiovascular health in the approximately 25 million people with a severe form of inherited hypercholesterolemia, called familial hypercholesterolemia (FH). The arterial endothelium in these individuals is potentially under multiple attacks caused by particles of both endogenous and exogenous origin. Thus, they (...) have a lifelong highly elevated level of circulating low density lipoprotein (LDL) cholesterol which drives premature atherosclerosis. The high levels of LDL particles, often associated with an elevated level of circulating lipoprotein(a) particles, are both capable of inducing and maintaining endothelial dysfunction. Such pre‐existing endothelial dysfunction can be exacerbated by exposure to SARS‐CoV‐2 viral particles, by exposure to fine particulate matter generated by climate change‐associated wildfires, and by dehydration during deadly heatwaves linked to the globally rising temperatures. The external factors can severely worsen the pre‐existing endothelial dysfunction, and thereby significantly increase the risk of a cardiovascular event in the exposed FH patients. (shrink)

Tick bite induced α‐gal syndrome (AGS) following consumption of mammalian meat is a recently described intriguing disease occurring worldwide. Here we argue that AGS and delayed allergy in general is an adaptive defence method against cancer. Our hypothesis synthesizes two lines of supporting evidence. First, allergy has been shown to have direct anti‐cancer effects with unknown mechanism. Second, eating processed meat was shown to be linked to developing cancer. Humans lost their genes encoding molecules α‐gal 30 MYA and Neu5Gc 2 (...) MYA, the latter co‐occurring with the start of using fire. These molecules are acquired from external sources, as tick bite for α‐gal and mammalian meat for Neu5Gc, the latter accumulating in tumors. The resulting specific delayed allergic response is a molecular adaptation to fight cancer. By further testing and applying our hypothesis, new avenues in cancer research and therapy will open that might save lives and decrease human suffering. (shrink)

Oxygenated derivatives of cholesterol (oxysterols) are widely distributed in nature, being found in the blood and tissues of animals and man as well as in foodstuff. They exhibit many biological activities which are of potential physiological, pathological or pharmacological importance. Many oxysterols have been found to be potent inhibitors of cholesterol biosynthesis and one or more oxysterols may play a role as the physiologic feedback regulator of cholesterol synthesis. Oxysterols also inhibit cell replication and have cytotoxic properties (...) effects which suggest that these sterols may participate in the regulation of cell proliferation and may be potentially useful as therapeutic agents for cancer. Furthermore, there is considerable evidence that oxysterols may be involved in the pathogenesis of atherosclerosis. Although the mechanism of action of oxysterols in all these instances is not well understood, the existence of cytosolic and microsomal proteins which bind oxysterols with high affinity and specificity suggests that this group of compounds may represent a family of intracellular regulatory molecules. (shrink)

Prevention of age-related disorders is increasingly in focus of health policies, and it is hoped that early intervention on processes of deterioration can promote healthier and longer lives. New opportunities to slow down the aging process are emerging with new fields such as personalized nutrition. Data-intensive research has the potential to improve the precision of existing risk factors, e.g., to replace coarse-grained markers such as blood cholesterol with more detailed multivariate biomarkers. In this paper, we follow an attempt to (...) develop a new aging biomarker. The vision among the project consortium, comprising both research and industrial partners, is that the new biomarker will be predictive of a range of age-related conditions, which may be preventable through personalized nutrition. We combine philosophical analysis and ethnographic fieldwork to explore the possibilities and challenges of managing aging through bodily signs that are not straightforwardly linked to symptomatic disease. We document how the improvement of measurement brings about new conceptual challenges of demarcating healthy and unhealthy states. Moreover, we highlight that the reframing of aging as risk has social and ethical implications, as it is generative of normative notions of what constitutes successful aging and good citizenship. (shrink)

In a series of recent papers, I have made three arguments about how to define “disease” and evaluate and apply possible definitions. First, I have argued that definitions should not be seen as traditional conceptual analyses, but instead as proposals about how to define and use the term “disease” in the future. Second, I have pointed out and attempted to address a challenge for dysfunction-requiring accounts of disease that I call the “line-drawing” problem: distinguishing between low-normal functioning and dysfunctioning. Finally, (...) I have used a dysfunction-requiring approach to argue that some extremely prevalent conditions, such as high blood pressure, high cholesterol, and ductal carcinoma in situ, are not diseases, but instead are risk factors. Four of the papers in this issue directly engage my previous work. In this commentary, I applaud the advances these authors make, address points of disagreement, and make suggestions about where the discussion should go next. (shrink)

In discussions of the ethics of human gene therapy, it has become standard to draw a distinction between the use of human gene transfer techniques to treat health problems and their use to enhance or improve normal human traits. Some dispute the normative force of this distinction by arguing that it is undercut by the legitimate medical use of human gene transfer techniques to prevent disease - such as genetic engineering to bolster immune function, improve the efficiency of DNA repair, (...) or add cellular receptors to capture and process cholesterol. If disease prevention is a proper goal of medicine, these critics argue, and the use of gene transfer techniques to enhance human health maintenance capacities will help achieve that goal, then the “treatment/enhancement‘ distinction cannot define the limits of legitimate gene therapy. In this paper, I argue that a line can be drawn between prevention and enhancement for gene therapy (and thus between properly medical and nonmedical uses of gene therapy), but only if one is willing to accept two rather old-fashioned claims: 1) Some health problems are best understood as if they were entities in their own right, reifiable as processes or parts in a biological system, with at least as much ontological objectivity and theoretical significance as the functions that they inhibit. 2) Legitimate preventive genetic health care should be limited to efforts to defend people from attack by these more robust pathological entities, rather than changing their bodies to evade social injustices. (shrink)

If validated, diet‐derived foreign microRNA absorption and function in consuming vertebrates would drastically alter our understanding of nutrition and ecology. RNA interference (RNAi) mechanisms of Caenorhabditis elegans are enhanced by uptake of environmental RNA and amplification and systemic distribution of RNAi effectors. Therapeutic exploitation of RNAi in treating human disease is difficult because these accessory processes are absent or diminished in most animals. A recent report challenged multiple paradigms, suggesting that ingested microRNAs (miRNAs) are transferred to blood, accumulate in tissues, (...) and exert canonical regulation of endogenous transcripts. Independent replication of these findings has been elusive, and multiple disconfirmatory findings have been published. In the face of mounting negative results, any additional positive reports must provide the proverbial “extraordinary proof” to support such claims. In this article, we review the evidence for and against a significant role for dietary miRNAs in influencing gene expression, and make recommendations for future studies.Also watch the Video Abstract. (shrink)

Causes often influence their effects via multiple routes. Moderate alcohol consumption can raise the level of HDL ('good') cholesterol, which in tum reduces the risk of heart disease. Unfortunately, moderate alcohol consumption can also increase the level of homocysteine, which in tum increases the risk of heart disease. The net or overall effect of alcohol consumption on heart disease will depend upon both of these routes, and no doubt upon many others as well. This is a familiar fact of (...) life for engineers and policy makers, one that often gives rise to unintended consequences. Suppose, for example, that the American Federal Aviation Administration were to institute new regulations requiring that aeroplanes be equipped with some expensive new safety feature. Would this regulation save lives? Not necessarily. Every dollar (or pound, or euro, or yen ... ) that an airline spends to upgrade its fleet is a dollar that must be recouped in some way, most likely through higher fares. Higher fares may, in tum, persuade some travellers to drive instead of fly- especially on shorter routes. But it is inherently more dangerous to drive a given route than to fly it, so the net effect of the new regulation may cost lives, rather than saving them (Glassner 1999: 188). (shrink)

Placebo cures. Global warming. Extraterrestrial life. Psychokinesis. In a time when scientific claims can sound as strange as science fiction--and can have a profound effect on individual life or public policy--assessing the merits of a far-out, supposedly scientific idea can be as difficult as it is urgent. Into the breach between helpless gullibility and unyielding skepticism steps physicist Robert Ehrlich, with an indispensable guide to making sense of "scientific" claims. A series of case studies of some of the most controversial (...) (and for the judging public, deeply vexing) topics in the natural and social sciences, Ehrlich's book serves as a primer for evaluating the evidence for the sort of strange-sounding ideas that can shape our lives. A much-anticipated follow-up to his popular Nine Crazy Ideas in Science, this book takes up issues close to readers' everyday reality--issues such as global warming, the dangers of cholesterol, and the effectiveness of placebos--as well as questions that resonate through (and beyond) civic life: Is intelligent design a scientific alternative to evolution? Is homosexuality primarily innate? Are people getting smarter or dumber? In each case, Ehrlich shows readers how to use the tools of science to judge the accuracy of strange ideas and the trustworthiness of ubiquitous "experts." As entertaining as it is instructive, his book will make the work of living wisely a bit easier and more reliable for scientists and nonscientists alike. (shrink)

The lipid‐bilayer component of cell membranes is an aqueous bimolecular aggregate characterized by a heterogeneous lateral organization of its molecular constituents. The heterogeneity may be sustained statically as well as dynamically. On the basis of recent experimental and theoretical progress in the study of the physical properties of lipid‐bilayer membranes, it is proposed that the dynamically heterogeneous membrane states are important for membrane functions such as transport of matter across the membrane and enzymatic activity. The heterogeneous membrane states undergo significant (...) structural changes in response to changes in compositional, thermodynamic, and environmental conditions. The diverse effects of a variety of molecular Compounds interacting with membranes, such as Cholesterol and drugs like anaesthetics, may be understood in terms of the ability of these compounds to affect and modulate the dynamic membrane heterogeneity. (shrink)

Definition of the problem: In 1997, Percutaneous Transluminal Coronary Angioplasty (PTCA) was performed in 138.001 cases in Germany. The standard indications, single vessel disease and badly controlled angina, are more and more extended to multivessel disease with and without severe angina, unstable or preinfarction angina, and acute myocardial infarction (AMI) itself. Dilating asymptomatic stenoses of more than 70–80% is a widely used indication, intending prophylaxis of complete occlusion and AMI. Actually there is no generally accepted guideline for the different new (...) indications, conservative versus invasive treatment schedule. It is difficult for the patient to get appropriate information before his decision between mechanical procedures and conservative methods; authentic informed consent actually seems to be in a very bad position. In 1992 the working group called ”Arbeitsgemeinschaft leitender kardiologischer Krankenhausärzte (ALKK)” decided to start a registry of all PTCA procedures, in order to gain knowledge about the present status of PTCA in Germany. Up to March 1999, 198.608 PTCA are logged.Arguments: Each PTCA was included on an intention-to-treat basis. The registry succeeded in a nearly complete recording with 98,6% of all PTCA procedures complete on March 17th, 1999. 93,5% of stenosed and 72,2% of the total occluded vessels were successfully dilated. In 4.729 cases (2,63%) the PTCA caused severe complications. The overall in-hospital mortality was only 0,5%, if the procedures done for AMI were excluded (including AMI it was 1,1%). The calculation of complications should be an essential part of the patients informed consent.Conclusion: Complete recording of all PTCA procedures is feasible even on a nationwide basis. Some results of the registry, as the indication control and the complication rate may help to realize a better doctor-patient-conversation on risks and benefits of either concept. The trend of many CHD patients is ”modern”: It should be done what can be done (mechanically), with results at once. Although said somehow paternalistic, this point of view cannot be tolerated: Proper informed consent today includes the realistic alternative of modern medicaments, especially those with an aggressive cholesterol lowering potency. (shrink)

Most of the discussion in bioethics and health policy concerning social responsibility for health has focused on society’s obligation to provide access to healthcare. While ensuring access to healthcare is an important social responsibility, societies can promote health in many other ways, such as through sanitation, pollution control, food and drug safety, health education, disease surveillance, urban planning and occupational health. Greater attention should be paid to strategies for health promotion other than access to healthcare, such as environmental and public (...) health and health research.Lifestyle plays a major role in most of the illnesses in industrialised nations.1 Six of the 10 leading factors contributing to the global burden of disease are lifestyle related: unsafe sex, high blood pressure, tobacco use, alcohol use, high cholesterol and obesity.2 Lifestyle-related illnesses also contribute to the rising costs of healthcare. Spending on healthcare accounts for about 16% of the gross domestic product in the USA, or US$1.9 trillion.3 Although smoking has declined steadily there since the 1960s, smoking-related medical expenses are still about US$75.5 billion per year.4 Obesity, which has been climbing in the past two decades, accounts for about US$75 billion in healthcare costs there each year.5 Alcoholism and drug addiction in the USA account for annual healthcare costs of about US$22.5 billion and US$12 billion, respectively.6,7 Federal government spending on healthcare relating to HIV/AIDS is over US$13 billion per year.8Given the well-documented relationship between lifestyle, disease burden and healthcare costs, it makes economic and medical sense to hold individuals morally responsible for their health-related choices. While this view has a great deal of intuitive appeal, it also faces numerous objections.9–12 First, holding individuals entirely responsible for their own health conflicts with medicine’s obligation to treat the sick and society’s obligation …. (shrink)

What counts as health or ill health? How do we deal with the fallibility of our own bodies? Should illness and disease be considered simply in biological terms, or should considerations of its emotional impact dictate our treatment of it? Our understanding of health and illness had become increasingly more complex in the modern world, as we are able to use medicine not only to fight disease but to control other aspects of our bodies, whether mood, blood pressure, or (...) class='Hi'>cholesterol. This collection of essays foregrounds the concepts of health and illness and patient experience within the philosophy of medicine, reflecting on the relationship between the ill person and society. Mental illness is considered alongside physical disease, and the important ramifications of society's differentiation between the two are brought to light. Health, Illness and Disease is a significant contribution to shaping the parameters of the evolving field of philosophy of medicine and will be of interest to medical practitioners and policy-makers as well as philosophers of science and ethicists. (shrink)

Previous studies have found that serum lipid levels independently associate with mental health problems in adulthood. However, little is known about the association between serum lipid levels and positive aspects of mental health such as resilience and self-esteem, which develop in adolescence. The aim of this study is to examine the association between serum lipid levels and resilience and self-esteem in Japanese adolescents. Data were pooled data from the Adachi Child Health Impact of Living Difficulty study in 2016 and 2018, (...) a school-based, cross-sectional study in Adachi City, Tokyo, Japan. Resilience of the child was assessed by caregivers, and self-esteem was self-identified via questionnaires. Serum lipid levels [total cholesterol, low-density lipoproteins, and high-density lipoproteins ] were assessed in school health checkup, in addition to height and weight measurements. Multiple linear regression was applied to investigate the association between standardized serum lipid levels and resilience and self-esteem. LDL showed inverse association with resilience [β = −1.26, 95% confidence interval = −2.39 to −0.14] after adjusting for child’s BMI, month of birth, sex, absence of parent, household income, caregiver’s mental health, and lifestyle. We also found an inverse association of total cholesterol and higher LDL cholesterol with self-esteem. HDL cholesterol was not associated with resilience and self-esteem. Among Japanese adolescent, total and LDL cholesterol may be biomarkers of resilience and self-esteem. (shrink)

Science progresses through debate and disagreement, and scientific controversies play a crucial role in the growth of scientific knowledge. However, not all controversies and disagreements are progressive in science. Sometimes, controversies can be pseudoscientific; in fact, bogus controversies, and what seem like genuine scientific disagreements, can be a distortion of science set up by non-scientific actors. Bogus controversies are detrimental to science because they can hinder scientific progress and eventually bias science-based decisions. The first goal of this paper is to (...) elucidate the distinction between bogus and genuine scientific controversies and provide a qualitative methodology, based on the literature on expertise, for distinguishing between the two. We will illustrate six epistemic criteria for distinguishing bogus from genuine scientific debates in science and medicine. This heuristic strategy applies directly to scientific reports, and it relies mostly on the social structure of science. We will then apply the above criteria to a case study: the controversy over statins, which are widely prescribed drugs for reducing the level of cholesterol and preventing cardiovascular disease. (shrink)

Many formerly incarcerated people have civil legal needs that can imperil their successful re-entry to society and, consequently, their health. We categorize these needs and assess their association with cardiovascular disease risk factors in a sample of recently released people. We find that having legal needs related to debt, public benefits, housing, or healthcare access is associated with psychosocial stress, but not uncontrolled high blood pressure or high cholesterol, in the first three months after release.

Domino's Pizza is testing “Domicopter” drones to deliver pizzas, which will compete with Taco Bell's “Tacocopter” drones. Not to be outdone, Amazon is working on an army of delivery drones that will cut out the postal service. In Denmark, farmers use drones to inspect fields for the appearance of harmful weeds, which reduces herbicide use as the drones directly apply pesticides only where it is needed. Environmentalists send drones into glacial caves or into deep waters, gathering data that would be (...) too dangerous or expensive for human scientists to procure. Federal Express dreams of pilotless aerial and terrestrial drones that will transport goods more cheaply, reliably, and safely than vehicles operated by humans. Human rights activists deploy drones over conflict zones, intelligently searching for and documenting abuses for both rhetorical and legal purposes. Aid agencies send unmanned drones to villages deep in jungles or behind enemy lines, maneuvering hazardous terrain to bring food and supplies to endangered populations. Medical researchers are experimenting with injecting drone blood cells into humans that can mimic good cholesterol carriers or identify and neutralize cancerous cells. Parents in Vermont are using flying drones to accompany children to school, giving a whole new meaning to helicopter parenting. And Pilobolus, a New York dance company, has choreographed a dance in which drones and humans engage each other in the most human of acts: the creation of art. (shrink)

An increasing number of patients receive diagnoses of disease without having any symptoms. These include diseases detected through screening programs, as incidental findings from unrelated investigations, or via routine checks of various biological variables like blood pressure or cholesterol. In this article, we draw on narrative identity theory to examine how the process of making sense of being diagnosed with asymptomatic disease can trigger certain overlooked forms of harm for patients. We show that the experience of asymptomatic disease can (...) involve ‘mismatches’ between one’s beliefs about one’s health status on the one hand, and bodily sensations or past experience on the other. Patients’ attempts to integrate these diagnoses into their self-narratives often involve either forming inaccurate beliefs about bodily sensations and/or past experience, or coming to believe that feelings and experience do not necessarily track or predict health status, leading to an ongoing sense of vulnerability to ill health. These resulting alterations in self-understanding can sometimes be considered harmful, in view of their implications for ascriptions of responsibility and ongoing anxiety. (shrink)

This paper provides empirical interpretation of the do(x)do(x) operator when applied to non-manipulable variables such as race, obesity, or cholesterol level. We view do(x)do(x) as an ideal intervention that provides valuable information on the effects of manipulable variables and is thus empirically testable. We draw parallels between this interpretation and ways of enabling machines to learn effects of untried actions from those tried. We end with the conclusion that researchers need not distinguish manipulable from non-manipulable variables; both types are (...) equally eligible to receive the do(x)do(x) operator and to produce useful information for decision makers. (shrink)

More than ever, the way we live our lives has become subject to our own decisionmaking. Our whole way of living, in particular what we do to our body, has become the expression of personal lifestyle choices. Because we can make changes to our body according to our own individual preferences, every aspect of our life begins to be seen as the result of individual and voluntary decisions. The comparison with advertising is pertinent here: we should no longer accept the (...) way we are but can choose from a variety of options. Go to any supermarket and look around: innumerable products are promoted because of their healthy ingredients, whether to lower our cholesterol or heighten our natural resistance. And, of course, we buy what is on offer. (shrink)

The objective of the study was to investigate the relationship between childhood IQ of parents and characteristics of their adult offspring. It was a prospective family cohort study linked to a mental ability survey of the parents and set in Renfrew and Paisley in Scotland. Participants were 1921-born men and women who took part in the Scottish Mental Survey in 1932 and the Renfrew/Paisley study in the 1970s, and whose offspring took part in the Midspan Family study in 1996. There (...) were 286 offspring from 179 families. Parental IQ was related to some, but not all characteristics of offspring. Greater parental IQ was associated with taller offspring. Parental IQ was inversely related to number of cigarettes smoked by offspring. Higher parental IQ was associated with better education, offspring social class and offspring deprivation category. There were no significant relationships between parental IQ and offspring systolic blood pressure, diastolic blood pressure, cholesterol, glucose, lung function, weight, body mass index, waist hip ratio, housing, alcohol consumption, marital status, car use and exercise. Structural equation modelling showed parental IQ associated with offspring education directly and mediated via parental social class. Offspring education was associated with offspring smoking and social class. The smoking finding may have implications for targeting of health education. (shrink)

Photo by Tingey Injury Law Firm on Unsplash ABSTRACT The coverage of healthcare costs allegedly brought about by people’s own earlier health-adverse behaviors is certainly a matter of justice. However, this raises the following questions: justice for whom? Is it right to take people’s past behaviors into account in determining their access to healthcare? If so, how do we go about taking those behaviors into account? These bioethical questions become even more complex when we consider them in the context of (...) a commitment to publicly funded, universal healthcare coverage. INTRODUCTION Healthcare coverage of lifestyle-related conditions is certainly a matter of justice. However, this raises the following justice-related question: Is it right to consider people’s past behaviors in determining their access to healthcare? If so, the methods of taking those behaviors into account must be fair and justifiable. This bioethical question becomes even more complex when we consider it in the context of a commitment to publicly funded, universal healthcare coverage. This paper takes an old, classic debate, evaluates newer approaches, and offers an argument favoring a combined approach which alters the liberal-egalitarian solution to account for social justice. ANALYSIS I. Causes of Disease If healthcare coverage were universal, irrespective of socioeconomic status and lifestyle, people would contribute to the cost of remedying the lifestyle-induced health problems of others. In the West, lifestyle-related diseases are burdensome.[i] This paper approaches this concern from a western lens that incorporates both a European tradition of “social safety nets” and an American tradition of personal freedoms. By taking such an approach, solutions to the consequences of one’s past behavior burdening others must consider an individual’s personal freedom to choose to act as he or she wishes, with the distributive social and economic equality of the many. The concept of disease caused by lifestyle and diet is proven. Many health conditions include behavioral risk factors. Multi-pack smoking increases the risk of chronic lung disease, while obesity increases the risk of type 2 diabetes. Inattention to high blood pressure, high cholesterol, and a lack of exercise leads to increased risks of coronary artery disease.[ii] While poor lifestyle choices certainly influence these conditions, their causes are multifactorial, and it is difficult to say that any single string of poor choices led to their development. In a scenario where two men excessively eat fast food for 20 years, several discrete factors impact whether any of them might suffer an ischemic-embolic stroke or not. Genetics, circumstances, and activity will also contribute to outcomes. II. Alcohol-Related End-Stage Liver Disease One paper suggests that alcohol-related end-stage liver disease (ARESLD) differs from other multifactorial disorders as alcohol alone causes the disease.[iii] It justifies attributing personal responsibility to patients with ARESLD because the condition develops only after the cumulative effects of large quantities of alcohol consumed from years to decades.[iv] However, the paper undermines its position by admitting that even the susceptibility to becoming an alcoholic has some degree of genetic predisposition.[v] Given the extreme scarcity of donor livers, some patients may be prioritized over others on the transplant waiting list. Since donor livers cannot be given to everyone, transplanting a liver into an alcoholic may result in death for competing candidates whose liver disease was not their fault. All else being equal, if bioethicists avoid claiming moral deficiency or judgment, those with apparently self-inflicted ARESLD will not be deprived of treatment but will have a lower priority for transplant.[vi] In contrast, another position suggests that it is often difficult to define what behaviors are punishable as these are largely personal and value-laden.[vii] Still, people do not support using their own resources to support the consequences of others’ poor choices, no matter how objective.[viii] In democratic societies, one must take into consideration community morals and values.[ix] Even if we were to punish people for their health-adverse behaviors, we could not logistically employ the vigorous and sustained efforts necessary to determine whose actions are morally weak.[x] III. The Liberal-Egalitarian Proposal One past argument proposes a liberal-egalitarian solution to manage personal responsibility for so-called “lifestyle diseases.”[xi] This Rawlsian system combines the European-style “social safety net” commitment to social and economic equality with the American liberal notion of pluralist toleration and personal freedoms. This idealized system aims to hold people responsible for their choices rather than the consequences to mitigate the downside of blaming those who might not be blameworthy. The approach avoids determining the questionable nature of luck and personal responsibility for health outcomes, fairness in the distribution of economic burden, and the intrusiveness required to practically determine who acts in a morally wrong and health-adverse way. The liberal-egalitarian model, a theory of distributive justice, has two facets: the liberal principle that people should be held accountable for their choices and the egalitarian principle that people who make the same choices should have the same outcomes.[xii] This model attempts to fuse responsibility with equity by seeking to reward good behavior and tax bad behavior rather than punish the consequences of the action and navigate who deserves treatment. For instance, the hospital bedside is not the appropriate place to introduce responsibility for one’s health outcomes.[xiii] This appeals to the reality that, at that time, discerning the true causes of disease was not plausible and to humanity in avoiding a heartless and cruel approach. An argument in favor of the liberal-egalitarian model considers its method of implementation. This approach assumes that the healthcare system treats all individuals regardless of their choices or ability to cover costs. The liberal-egalitarian model also assumes that a certain adverse health condition is related, statistically speaking, to the consumption of a certain good and that good can be taxed. As such, it proposes to tax the consumption of that good to finance the collective burden which arises from that good’s consumption rather than require individuals to pay for their own treatment. In the example of ARESLD, the recommended solution would be taxing all alcohol. While a systematic infrastructure is not explicit, there is the implication that a per-unit tax can be imposed on alcohol so the total tax revenue would make up for the additional healthcare costs due to consumption.[xiv] Upholding the principle that all people who make the same choices should face the same costs, all consumers of alcohol would pay the same tax, regardless of factors such as genetic predisposition to alcoholism, lifestyle, or expected cost of treatment. Upholding the principle of individual responsibility, this model does not deny treatment to anyone, neutralizing factors outside that individual’s control by imposing the tax ex-ante. Other people are not burdened by those who consume the good. People who consume alcohol face a burden proportional to the amount consumed. This tax-based implementation is justified so long as the tax is not prohibitively high for the average consumer. Further, the model mitigates concerns over the intrusiveness of ascribing morality to health-adverse behaviors. IV. Moral and Social Arguments Against the Liberal-Egalitarian Position Arguments against the liberal-egalitarian model concerns its many assumptions. First, this model assumes that consumption of such goods is directly related to the health outcome and that these goods can be taxed.[xv] Certain people genetically predisposed to alcoholism would be predisposed to consume more alcohol. The model falls short when applied to scenarios where health outcomes are not consumption-based, such as engaging in unsafe sex or abstaining from healthy lifestyle choices like exercise. Second, some might argue that the liberal-egalitarian model fails to remain neutral. Residual moral judgments tied to consumption choices introduce non-neutrality. Although taxation in free societies is determined by democratic procedures rather than by individuals in the healthcare system, moral and value-based judgments will be implicit in deciding what behaviors are taxable, such as the purchase of cigarettes. Third, the liberal-egalitarian model fails to determine whether one’s behavior is autonomous, as socio-cultural-economic factors may influence it and behavior is more a product of society, peer pressure, or income. Those also may reflect systemic inequalities. Therefore, this model, which rewards, or taxes based solely on decisions, regardless of their consequences and motivations, fails to consider that a person’s decisions may not be completely autonomous. V. Libertarian Arguments Against the Liberal-Egalitarian Model a. State Intrusiveness as Counter to the Liberal-Egalitarian Model Last, there is a libertarian worry that if the state guarantees universal healthcare coverage to all people, the state will have to become highly intrusive and investigate people’s morals.[xvi] At least one-third of all disease burden in North America, Europe, and the Asia-Pacific is attributable to lifestyle measures such as tobacco smoking, alcohol consumption, high cholesterol, and obesity.[xvii] With these various lifestyles, it is not likely to agree on what conduct to tax or condemn.[xviii] The fine-toothed comb required to determine whether each citizen has been engaging in these behaviors would intrude on daily life and personal freedom. Libertarians champion the argument that impractical intrusiveness would result from universal healthcare, and such a degree of intrusiveness would likely be universally unacceptable.[xix] The liberal-egalitarian model mitigates the libertarian worry about state intrusiveness as it does not involve prying into one’s life and choices other than taxing goods. A liberal state should ideally be neutral to how people decide to live their lives. In all, libertarians can rest assured that the liberal-egalitarian tax-based model, through its ex-ante implementation, will require no prying state eyes. States that provide universal healthcare coverage and wish to condemn certain misconduct do not need to become overly intrusive to carry out measures to hold individuals accountable. b. Fairness Another libertarian worry regarding the guarantee of universal healthcare coverage in the context of lifestyle-driven diseases is that the public will be burdened unfairly with covering others’ ill-advised mistakes or bad luck. An ideal system to address this worry would link treatment or payment for treatment with whatever behavior caused that need.[xx] The distribution of burdens should be linked to how different individuals contributed to the creation of those burdens. Applied to health policy, we should ask how the need for a certain treatment arose when determining how to distribute its cost.[xxi] The liberal-egalitarian model aspires to hold individuals responsible for their choices, not for the consequences of such choices. This model significantly mitigates the libertarian worry over unfair burdens for covering other people’s mistakes or social conditions, which lead to those bad outcomes, by ensuring to not burden others with any of the costs for the treatment of people who decide to engage in certain health-adverse behaviors. The aforementioned taxation-based system would only tax those who also engage in the health-adverse behavior through consumption, and that tax directly pays for the necessary collective treatment. As such, those who do not consume the good are not involved with the payment scheme, while those who do consume the good are responsible for payment in a matter proportional to the amount of the good they have consumed. VI. Universal Coverage Taking a step back, one should consider whether these worries regarding the coverage of apparently self-inflicted health conditions in the context of universal healthcare are worthwhile issues. One perspective raises what is called the culturally imagined objection — an idea erroneously held by many that sick people, especially those who are poor and uneducated, bring these illnesses upon themselves due to poor decision-making and irresponsible risk-taking.[xxii] This perspective critiques the uniquely American view that, since individuals are free to choose their lifestyles, they should bear the costs of their lifestyle.[xxiii] Taking this argument further, some (perhaps the strongly libertarian) would say that the poor health status among many individuals is the price individuals must pay for their American way of life and the liberty and freedom to live as they wish. However, people should not completely punish individuals for their health-adverse behaviors because these choices are largely pre-determined by a person’s socioeconomic influences.[xxiv] The outcomes from these allegedly ill-advised behaviors, which largely affect poorer people, are not just poor behavior but rather a public health crisis. Perhaps the state and its people should take collective responsibility and cover the costs of treatment for those health outcomes without question, as a form of public service. Rather than worrying about accountability and taxing bad behavior or intrusiveness into personal decisions, some might argue that people need to collectively take responsibility for reducing the overarching systemic inequalities and covering the associated treatment costs as a measure of public health. VII. Proposed Solution Given the strengths of the liberal-egalitarian model and taking into account libertarian and social justice-oriented objections, an ideal solution for the coverage of lifestyle-related health problems needs to consider the complex relationship between a person’s behaviors and their apparent health outcomes. It must consider how society as a whole passes judgment on behaviors and how to take into account that many health-adverse decisions are not truly autonomous decisions, as various genetic and socioeconomic factors influence them. An ideal solution combines the liberal-egalitarian tax-based model with the social justice concerns of universal coverage. Whatever the cost for the treatment of medical issues resulting in part or entirely from lifestyle and diet, taxes collected from spending associated with the behavior (like the purchase of alcohol, junk food, and cigarettes) ex-ante should fund 50 percent of the cost of treatment, while the universal healthcare taxation scheme should include the other 50 percent. Such a system would provide an incentive to avoid the purchases that can lead to unhealthy consumption and make healthier choices, slightly punish and discourage such purchases through taxation, yet not overly punish people whose outcomes may have more to do with socioeconomic factors and genetics. Adding public responsibility demonstrates acknowledgement that health care is in the public interest and can mitigate public health inequalities. This solution would fuse personal responsibility with the public responsibility of state-sponsored social improvement while ensuring that all people have fair access to necessary treatment, no matter their ability to pay. CONCLUSION The 50-50 system this paper proposes reflects both justice and personal responsibility in covering healthcare costs allegedly brought about by people’s own health-adverse behaviors. By allocating tax revenue from consumption that contributes or even alone causes poor health outcomes, such a system incorporates personal responsibility. By using general tax revenue for health care, such a system would meet the libertarian requirement of providing care without any moral investigation of past behaviors and the social justice consideration of providing health care to those who may have unwittingly ventured into ill-health due to systemic injustice, socioeconomics, or genetics. - [i] Cappelen, A. W. (2005). Responsibility in health care: A liberal egalitarian approach. Journal of Medical Ethics, 31(8), 476–480. https://doi.org/10.1136/jme.2004.010421 [ii] Moss, A. H. (1991). Should alcoholics compete equally for liver transplantation? JAMA: The Journal of the American Medical Association, 265(10), 1295–1298. https://doi.org/10.1001/jama.1991.03460100097032 [iii] Moss, p. 1295-1298. [iv] Moss, p. 1296. [v] Moss, p. 1295-1298. [vi] Moss, p. 1295-1298. [vii] Cohen, C. IS THIS SUPPOSED TO BE COHEN AND BENJAMIN (1991). Alcoholics and liver transplantation. JAMA: The Journal of the American Medical Association, 265(10), 1299–1301. https://doi.org/10.1001/jama.1991.03460100101033 [viii] Cohen, p. 1299-1301. [ix] Moss, p. 1297. [x] Cohen, p. 1300. [xi] Cappelen, p. 478-480. [xii] Cappalen, p. 478-480. [xiii] Cappelen, p.479. [xiv] Cappelen, p. 479. [xv] Cappelen, p. 479 [xvi] Cohen, p. 1301. [xvii] Cappelen, p. 478. [xviii] Cohen, p. 1299-1301. [xix] Cohen, p. 1301. [xx] Cappelen, p. 476-480. [xxi] Cappelen, p. 476-480. [xxii] Kawachi, I. (2005). Why the United States is not number one in Health. Healthy, Wealthy, and Fair, 18–33. https://doi.org/10.1093/acprof:oso/9780195170665.003.0013 [xxiii] Kawachi, p. 18-33. [xxiv] Kawachi, p. 18-33. (shrink)

Mammalian AMP‐activated protein kinase is the central component of a protein kinase cascade which inactivates three key enzymes involved in the synthesis or release of free fatty acids and cholesterol inside the cell. The kinase cascade is activated by elevation of AMP, and perhaps also by fatty acid and cholesterol metabolites. The system may fulfil a protective function, preventing damage caused by depletion of ATP or excessive intracellular release of free lipids, a type of stress response. Recent evidence (...) suggests that it may have been in existence for at least a billion years, since a very similar protein kinase cascade is present in higher plants. This system therefore represents an early eukaryotic protein kinase cascade, which is unique in that it is regulated by intracellular metabolites rather than extracellular signals or cell cycle events. (shrink)

While the COVID-19 pandemic riveted public attention on questions regarding how to respond reasonably to risk of illness, everyday medical care involves more mundane forms of pharmaceutical risk management for conditions like high blood pressure, prediabetes, or high cholesterol. This essay, and the collection it introduces, explore medicalization of risk as a theological problem, drawing on resources such as the Sermon on the Mount that caution us about the potential dangers of risk management to Christian discipleship. Medicalization of risk (...) threatens to become an idol that promises immanent security at the cost of one’s relationship with God and others. It misleads contemporary society as to the true human end and medicine’s own capabilities to provide temporal salvation. The essays in this special issue illustrate these problems with respect to pharmaceutical risk management. (shrink)

Cardiovascular disease is a major complication of type 2 diabetes mellitus. In addition to traditional risk factors, psychological determinants play an important role in CVD risk. This study applied Deep Neural Network to develop a CVD risk prediction model and explored the bio-psycho-social contributors to the CVD risk among patients with T2DM. From 2017 to 2020, 834 patients with T2DM were recruited from the Department of Endocrinology, Affiliated Hospital of Harbin Medical University, China. In this cross-sectional study, the patients' bio-psycho-social (...) information was collected through clinical examinations and questionnaires. The dataset was randomly split into a 75% train set and a 25% test set. DNN was implemented at the best performance on the train set and applied on the test set. The receiver operating characteristic curve analysis was used to evaluate the model performance. Of participants, 272 were diagnosed with CVD. The developed ensemble model for CVD risk achieved an area under curve score of 0.91, accuracy of 87.50%, sensitivity of 88.06%, and specificity of 87.23%. Among patients with T2DM, the top five predictors in the CVD risk model were body mass index, anxiety, depression, total cholesterol, and systolic blood pressure. In summary, machine learning models can provide an automated identification mechanism for patients at CVD risk. Integrated treatment measures should be taken in health management, including clinical care, mental health improvement, and health behavior promotion. (shrink)

Photo by Tingey Injury Law Firm on Unsplash ABSTRACT The coverage of healthcare costs allegedly brought about by people’s own earlier health-adverse behaviors is certainly a matter of justice. However, this raises the following questions: justice for whom? Is it right to take people’s past behaviors into account in determining their access to healthcare? If so, how do we go about taking those behaviors into account? These bioethical questions become even more complex when we consider them in the context of (...) a commitment to publicly funded, universal healthcare coverage. INTRODUCTION Healthcare coverage of lifestyle-related conditions is certainly a matter of justice. However, this raises the following justice-related question: Is it right to consider people’s past behaviors in determining their access to healthcare? If so, the methods of taking those behaviors into account must be fair and justifiable. This bioethical question becomes even more complex when we consider it in the context of a commitment to publicly funded, universal healthcare coverage. This paper takes an old, classic debate, evaluates newer approaches, and offers an argument favoring a combined approach which alters the liberal-egalitarian solution to account for social justice. ANALYSIS l. Causes of Disease If healthcare coverage were universal, irrespective of socioeconomic status and lifestyle, people would contribute to the cost of remedying the lifestyle-induced health problems of others. In the West, lifestyle-related diseases are burdensome.[1] This paper approaches this concern from a western lens that incorporates both a European tradition of “social safety nets” and an American tradition of personal freedoms. By taking such an approach, solutions to the consequences of one’s past behavior burdening others must consider an individual’s personal freedom to choose to act as he or she wishes, with the distributive social and economic equality of the many. The concept of disease caused by lifestyle and diet is proven. Many health conditions include behavioral risk factors. Multi-pack smoking increases the risk of chronic lung disease, while obesity increases the risk of type 2 diabetes. Inattention to high blood pressure, high cholesterol, and a lack of exercise leads to increased risks of coronary artery disease.[2] While poor lifestyle choices certainly influence these conditions, their causes are multifactorial, and it is difficult to say that any single string of poor choices led to their development. In a scenario where two men excessively eat fast food for 20 years, several discrete factors impact whether any of them might suffer an ischemic-embolic stroke or not. Genetics, circumstances, and activity will also contribute to outcomes. ll. Alcohol-Related End-Stage Liver Disease One paper suggests that alcohol-related end-stage liver disease (ARESLD) differs from other multifactorial disorders as alcohol alone causes the disease.[3] It justifies attributing personal responsibility to patients with ARESLD because the condition develops only after the cumulative effects of large quantities of alcohol consumed from years to decades.[4] However, the paper undermines its position by admitting that even the susceptibility to becoming an alcoholic has some degree of genetic predisposition.[5] Given the extreme scarcity of donor livers, some patients may be prioritized over others on the transplant waiting list. Since donor livers cannot be given to everyone, transplanting a liver into an alcoholic may result in death for competing candidates whose liver disease was not their fault. All else being equal, if bioethicists avoid claiming moral deficiency or judgment, those with apparently self-inflicted ARESLD will not be deprived of treatment but will have a lower priority for transplant.[6] In contrast, another position suggests that it is often difficult to define what behaviors are punishable as these are largely personal and value-laden.[7] Still, people do not support using their own resources to support the consequences of others’ poor choices, no matter how objective.[8] In democratic societies, one must take into consideration community morals and values.[9] Even if we were to punish people for their health-adverse behaviors, we could not logistically employ the vigorous and sustained efforts necessary to determine whose actions are morally weak.[10] lll. The Liberal-Egalitarian Proposal One past argument proposes a liberal-egalitarian solution to manage personal responsibility for so-called “lifestyle diseases.”[11] This Rawlsian system combines the European-style “social safety net” commitment to social and economic equality with the American liberal notion of pluralist toleration and personal freedoms. This idealized system aims to hold people responsible for their choices rather than the consequences to mitigate the downside of blaming those who might not be blameworthy. The approach avoids determining the questionable nature of luck and personal responsibility for health outcomes, fairness in the distribution of economic burden, and the intrusiveness required to practically determine who acts in a morally wrong and health-adverse way. The liberal-egalitarian model, a theory of distributive justice, has two facets: the liberal principle that people should be held accountable for their choices and the egalitarian principle that people who make the same choices should have the same outcomes.[12] This model attempts to fuse responsibility with equity by seeking to reward good behavior and tax bad behavior rather than punish the consequences of the action and navigate who deserves treatment. For instance, the hospital bedside is not the appropriate place to introduce responsibility for one’s health outcomes.[13] This appeals to the reality that, at that time, discerning the true causes of disease was not plausible and to humanity in avoiding a heartless and cruel approach. An argument in favor of the liberal-egalitarian model considers its method of implementation. This approach assumes that the healthcare system treats all individuals regardless of their choices or ability to cover costs. The liberal-egalitarian model also assumes that a certain adverse health condition is related, statistically speaking, to the consumption of a certain good and that good can be taxed. As such, it proposes to tax the consumption of that good to finance the collective burden which arises from that good’s consumption rather than require individuals to pay for their own treatment. In the example of ARESLD, the recommended solution would be taxing all alcohol. While a systematic infrastructure is not explicit, there is the implication that a per-unit tax can be imposed on alcohol so the total tax revenue would make up for the additional healthcare costs due to consumption.[14] Upholding the principle that all people who make the same choices should face the same costs, all consumers of alcohol would pay the same tax, regardless of factors such as genetic predisposition to alcoholism, lifestyle, or expected cost of treatment. Upholding the principle of individual responsibility, this model does not deny treatment to anyone, neutralizing factors outside that individual’s control by imposing the tax ex-ante. Other people are not burdened by those who consume the good. People who consume alcohol face a burden proportional to the amount consumed. This tax-based implementation is justified so long as the tax is not prohibitively high for the average consumer. Further, the model mitigates concerns over the intrusiveness of ascribing morality to health-adverse behaviors. lV. Moral and Social Arguments Against the Liberal-Egalitarian Position Arguments against the liberal-egalitarian model concerns its many assumptions. First, this model assumes that consumption of such goods is directly related to the health outcome and that these goods can be taxed.[15] Certain people genetically predisposed to alcoholism would be predisposed to consume more alcohol. The model falls short when applied to scenarios where health outcomes are not consumption-based, such as engaging in unsafe sex or abstaining from healthy lifestyle choices like exercise. Second, some might argue that the liberal-egalitarian model fails to remain neutral. Residual moral judgments tied to consumption choices introduce non-neutrality. Although taxation in free societies is determined by democratic procedures rather than by individuals in the healthcare system, moral and value-based judgments will be implicit in deciding what behaviors are taxable, such as the purchase of cigarettes. Third, the liberal-egalitarian model fails to determine whether one’s behavior is autonomous, as socio-cultural-economic factors may influence it and behavior is more a product of society, peer pressure, or income. Those also may reflect systemic inequalities. Therefore, this model, which rewards, or taxes based solely on decisions, regardless of their consequences and motivations, fails to consider that a person’s decisions may not be completely autonomous. V. Libertarian Arguments Against the Liberal-Egalitarian Model a. State Intrusiveness as Counter to the Liberal-Egalitarian Model Last, there is a libertarian worry that if the state guarantees universal healthcare coverage to all people, the state will have to become highly intrusive and investigate people’s morals.[16] At least one-third of all disease burden in North America, Europe, and the Asia-Pacific is attributable to lifestyle measures such as tobacco smoking, alcohol consumption, high cholesterol, and obesity.[17] With these various lifestyles, it is not likely to agree on what conduct to tax or condemn.[18] The fine-toothed comb required to determine whether each citizen has been engaging in these behaviors would intrude on daily life and personal freedom. Libertarians champion the argument that impractical intrusiveness would result from universal healthcare, and such a degree of intrusiveness would likely be universally unacceptable.[19] The liberal-egalitarian model mitigates the libertarian worry about state intrusiveness as it does not involve prying into one’s life and choices other than taxing goods. A liberal state should ideally be neutral to how people decide to live their lives. In all, libertarians can rest assured that the liberal-egalitarian tax-based model, through its ex-ante implementation, will require no prying state eyes. States that provide universal healthcare coverage and wish to condemn certain misconduct do not need to become overly intrusive to carry out measures to hold individuals accountable. b. Fairness Another libertarian worry regarding the guarantee of universal healthcare coverage in the context of lifestyle-driven diseases is that the public will be burdened unfairly with covering others’ ill-advised mistakes or bad luck. An ideal system to address this worry would link treatment or payment for treatment with whatever behavior caused that need.[20] The distribution of burdens should be linked to how different individuals contributed to the creation of those burdens. Applied to health policy, we should ask how the need for a certain treatment arose when determining how to distribute its cost.[21] The liberal-egalitarian model aspires to hold individuals responsible for their choices, not for the consequences of such choices. This model significantly mitigates the libertarian worry over unfair burdens for covering other people’s mistakes or social conditions, which lead to those bad outcomes, by ensuring to not burden others with any of the costs for the treatment of people who decide to engage in certain health-adverse behaviors. The aforementioned taxation-based system would only tax those who also engage in the health-adverse behavior through consumption, and that tax directly pays for the necessary collective treatment. As such, those who do not consume the good are not involved with the payment scheme, while those who do consume the good are responsible for payment in a matter proportional to the amount of the good they have consumed. Vl. Universal Coverage Taking a step back, one should consider whether these worries regarding the coverage of apparently self-inflicted health conditions in the context of universal healthcare are worthwhile issues. One perspective raises what is called the culturally imagined objection — an idea erroneously held by many that sick people, especially those who are poor and uneducated, bring these illnesses upon themselves due to poor decision-making and irresponsible risk-taking.[22] This perspective critiques the uniquely American view that, since individuals are free to choose their lifestyles, they should bear the costs of their lifestyle.[23] Taking this argument further, some (perhaps the strongly libertarian) would say that the poor health status among many individuals is the price individuals must pay for their American way of life and the liberty and freedom to live as they wish. However, people should not completely punish individuals for their health-adverse behaviors because these choices are largely pre-determined by a person’s socioeconomic influences.[24] The outcomes from these allegedly ill-advised behaviors, which largely affect poorer people, are not just poor behavior but rather a public health crisis. Perhaps the state and its people should take collective responsibility and cover the costs of treatment for those health outcomes without question, as a form of public service. Rather than worrying about accountability and taxing bad behavior or intrusiveness into personal decisions, some might argue that people need to collectively take responsibility for reducing the overarching systemic inequalities and covering the associated treatment costs as a measure of public health. Vll. Proposed Solution Given the strengths of the liberal-egalitarian model and taking into account libertarian and social justice-oriented objections, an ideal solution for the coverage of lifestyle-related health problems needs to consider the complex relationship between a person’s behaviors and their apparent health outcomes. It must consider how society as a whole passes judgment on behaviors and how to take into account that many health-adverse decisions are not truly autonomous decisions, as various genetic and socioeconomic factors influence them. An ideal solution combines the liberal-egalitarian tax-based model with the social justice concerns of universal coverage. Whatever the cost for the treatment of medical issues resulting in part or entirely from lifestyle and diet, taxes collected from spending associated with the behavior (like the purchase of alcohol, junk food, and cigarettes) ex-ante should fund 50 percent of the cost of treatment, while the universal healthcare taxation scheme should include the other 50 percent. Such a system would provide an incentive to avoid the purchases that can lead to unhealthy consumption and make healthier choices, slightly punish and discourage such purchases through taxation, yet not overly punish people whose outcomes may have more to do with socioeconomic factors and genetics. Adding public responsibility demonstrates acknowledgement that health care is in the public interest and can mitigate public health inequalities. This solution would fuse personal responsibility with the public responsibility of state-sponsored social improvement while ensuring that all people have fair access to necessary treatment, no matter their ability to pay. CONCLUSION The 50-50 system this paper proposes reflects both justice and personal responsibility in covering healthcare costs allegedly brought about by people’s own health-adverse behaviors. By allocating tax revenue from consumption that contributes or even alone causes poor health outcomes, such a system incorporates personal responsibility. By using general tax revenue for health care, such a system would meet the libertarian requirement of providing care without any moral investigation of past behaviors and the social justice consideration of providing health care to those who may have unwittingly ventured into ill-health due to systemic injustice, socioeconomics, or genetics. - [1] Cappelen, A. W. (2005). Responsibility in health care: A liberal egalitarian approach. Journal of Medical Ethics, 31(8), 476–480. https://doi.org/10.1136/jme.2004.010421 [2] Moss, A. H. (1991). Should alcoholics compete equally for liver transplantation? JAMA: The Journal of the American Medical Association, 265(10), 1295–1298. https://doi.org/10.1001/jama.1991.03460100097032 [3] Moss, p. 1295-1298. [4] Moss, p. 1296. [5] Moss, p. 1295-1298. [6] Moss, p. 1295-1298. [7] Cohen, C. IS THIS SUPPOSED TO BE COHEN AND BENJAMIN (1991). Alcoholics and liver transplantation. JAMA: The Journal of the American Medical Association, 265(10), 1299–1301. https://doi.org/10.1001/jama.1991.03460100101033 [8] Cohen, p. 1299-1301. [9] Moss, p. 1297. [10] Cohen, p. 1300. [11] Cappelen, p. 478-480. [12] Cappalen, p. 478-480. [13] Cappelen, p.479. [14] Cappelen, p. 479. [15] Cappelen, p. 479 [16] Cohen, p. 1301. [17] Cappelen, p. 478. [18] Cohen, p. 1299-1301. [19] Cohen, p. 1301. [20] Cappelen, p. 476-480. [21] Cappelen, p. 476-480. [22] Kawachi, I. (2005). Why the United States is not number one in Health. Healthy, Wealthy, and Fair, 18–33. https://doi.org/10.1093/acprof:oso/9780195170665.003.0013 [23] Kawachi, p. 18-33. [24] Kawachi, p. 18-33. (shrink)

Inconsistencies between scientific theories have been studied, by and large, from the perspective of paraconsistent logic. This approach considered the formal properties of theories and the structure of inferences one can legitimately draw from theories. However, inconsistencies can be also analysed from the perspective of modelling practices, in particular how modelling practices may lead scientists to form opinions and attitudes that are different, but not necessarily inconsistent. In such cases, it is preferable to talk about disagreement, rather than inconsistency. Disagreement (...) may originate in, or concern, a number of epistemic, socio-political or psychological factors. In this paper, we offer an account of the ‘loci and reasons’ for disagreement at different stages of the scientific process. We then present a controversial episode in the health sciences: the studies on hypercholesterolemia. The causes and effects of high levels of cholesterol in blood have been long and hotly debated, to the point of deserving the name of ‘cholesterol wars’; the debate, to be sure, isn’t settled yet. In this contribution, we focus on some selected loci and reasons for disagreement that occurred between 1920 and 1994 in the studies on hypercholesterolemia. We hope that our analysis of ‘loci and reasons’ for disagreement may shed light on the cholesterol wars, and possibly on other episodes of scientific disagreement. (shrink)

Hedgehog proteins are of pivotal importance for development and maintenance of tissue patterns in adult organisms. Despite the role of Hedgehogs in differentiation and tumorigenesis, signal transduction of Hedgehog remains a relatively uncharted area of signalling biochemistry. For proper Hedgehog distribution into tissues, two highly unusual covalent modifications are necessary, palmitoylation of a secreted protein and the attachment of a cholesterol group, making Hedgehog the only established sterolated protein in nature. Hedgehog exerts its function via two membrane‐bound receptors, Patched (...) and Smoothened; presumably, Patched transports a cholesterol derivate out of cells which inhibits Smoothened. Binding of Hedgehog to Patched impedes this proposed pump function and thus Inhibition of Smoothened, which leads to expression of genetic Hedgehog targets via relief of transcriptional repression. These atypical features make Hedgehog physiology unique in biology and may explain why this field has attracted such significant attention. BioEssays 26:387–394, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

SUVs are the safest vehicle because they're so large-right? Wrong! That's the advertising pitch, but in 2000, they had the highest rollover rate (36%) of any vehicle type involved in fatal accidents. Yet two years later their safety myth was still so strong that one of four vehicles sold in the U.S. was an SUV. The world of spin we live in is full of such potentially hazardous illusions. We need to know if particular foods can hurt us with Salmonella (...) or cholesterol, whether our government is truthful in its reasons for waging war, what problems a political candidate may cause or resolve if elected, and whether the items we purchase are durable or junk. But gaining those insights can be challenging when so many of the illusions surrounding us are deliberately created. As a civil-litigation attorney for over twenty-five years, Randy Kasten has heard thousands of lies. He has witnessed that those who dispense the information we need to make decisions-advertisers, salespeople, politicians, and the media-often have a vested interest in manipulating us. Truth's biggest enemies are the people whose job it is to sell us incomplete versions of the facts and our willingness to believe what we want to believe. Often, we believe what we believe because it is the only story available. To help us see through deceptions of all types, Kasten discusses eight kinds of lies and what we can do about them, as well as methods for discerning the truth gleaned from his practice of law. Other topics include advertising magic, thirty-six places where the truth hides, lessons from science, the media and misinformation, and how we fool ourselves. Altogether, he provides a unique tool for enabling us to make decisions that will lead to more prosperity, better health, greater intimacy, and a life based on lasting values. (shrink)

Recently developed super‐resolution microscopy techniques are changing our understanding of lipid rafts and membrane organisation in general. The lipid raft hypothesis postulates that cholesterol can drive the formation of ordered domains within the plasma membrane of cells, which may serve as platforms for cell signalling and membrane trafficking. There is now a wealth of evidence for these domains. However, their study has hitherto been hampered by the resolution limit of optical microscopy, making the definition of their properties problematic and (...) contentious. New microscopy techniques circumvent the resolution limit and, for the first time, allow the fluorescence imaging of structures on length scales below 200 nm. This review describes such techniques, particularly as applied to the study of membrane organisation, synthesising newly emerging facets of lipid raft biology into a state‐of‐the art model.Editor's suggested further reading in BioEssays: Super‐resolution imaging prompts re‐thinking of cell biology mechanisms Abstract and Quantitative analysis of photoactivated localization microscopy (PALM) datasets using pair‐correlation analysis Abstract. (shrink)

Oxycholesterols (OS) are formed from cholesterol or its immediate precursors by enzymatic or free radical action in vivo, or they may be derived from food. OS exhibit a wide spectrum of biological activities. In OS cytotoxicity, several mechanisms seem to be involved: e.g. inhibition of HMG‐CoA reductase activity, antiproliferative action, apoptosis induction, replacement of cholesterol by OS in membranes followed by changes in cellular membrane structure and functionality, and immune system functions alteration. Furthermore, OS may be mutagenic and (...) carcinogenic and may serve as intracellular signaling or regulatory molecules. Here we review OS cellular activities with special attention to the cytotoxic action in vivo and in vitro using experimental models. BioEssays 28: 387–398, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

This article explores some implications of the increasing reliance on clinical trials in contemporary health care, particularly health care payers’ efforts to use them in the so-called fourth hurdle decisions. How do these agencies manage medical uncertainty given the desire to produce clear guidelines for clinicians? Their solutions take account of trials in at least two ways, reflecting broader debates about the meaning of these medical experiments. Trials can be read as either ‘‘proofs of protocol’’—straightforward guides to action with individual (...) drugs in specific populations—or ‘‘proofs of principle’’— where extrapolation is made possible through an appeal to underlying biological mechanisms. These contrasting readings of trials are illustrated with reference to guidelines on heart disease prevention/cholesterol reduction using statins among the elderly in North America and the United Kingdom. Uncertainty in these cases does not lead to inertia but solutions use different fixed points to aid navigation, including both physiological principles and moral values. (shrink)

While there has been a significant amount of scholarship done on health and risk in relation to public health and disease prevention, relatively little attention has been paid to therapeutic interventions which seek to manage risks as bodily, and biological, matters. This article elucidates the distinct qualities and logics of these two different approaches to risk management, in relation to Michel Foucault’s conception of the two poles of biopower, that is, a biopolitics of the population and an anatomo-politics of the (...) human body. Using a case study of contemporary addiction biomedicine, the article examines the development and deployment of treatments for addiction that seek to reduce the risks of relapse to drug use, and relates this case to other risk-reducing (but non-curative) medications, particularly cholesterol-reducing medications. The notion of a ‘disease of risk’ is developed in order to identify a range of medical conditions that bear a family resemblance, insofar as they are pharmaceutically managed with risk-reducing medications, and bound up within what is described as a contemporary ‘risk anatomo-politics’. (shrink)