The prevalence of obesity, metabolic syndrome, and the associated long-term chronic diseases (cardiovascular disease, type II diabetes, cancer, Alzheimer’s disease, depression) have reached epidemic levels in the United States and Western nations. In response to this public health calamity, the author of this paper presents and defends a novel bioethical argument: the consistency argument for outlawing SSBs (sugar-sweetened beverages) for child consumption (the “consistency argument”). This argument’s radical conclusion states that the government is justified in outlawing SSBs consumption (...) for child consumption. The reasoning is as follows: if one accepts that the physical harm caused by chronic alcohol consumption justifies the government outlawing alcoholic beverages for child consumption, and there is strong evidence that comparable physical harms result from chronic SSBs consumption, then, _mutatis mutandis_, the government is also justified in outlawing child consumption of SSBs. To support this argument, the author provides extensive evidence based on epidemiological observational studies, interventional studies, controlled trials, large meta-analyses, and the pathophysiology and biological mechanisms of action behind SSBs and chronic disease. Chronic consumption of large doses of SSBs and alcoholic beverages both drive the same diseases: obesity and insulin resistance, cardiovascular disease, hypertension, and cancer. Chronic SSB consumption carries the additional risk of Alzheimer’s disease, dementia, and depression. The author concludes this paper by considering prominent objections to the consistency argument, and then demonstrating that each objection is unsound. (shrink)

The definition of metabolic syndrome has been, and still is, extremely controversial. My purpose is not to give a solution to the associated debate but to argue that the controversy is at least partially due to the different ‘causal content’ of the various definitions: their theoretical validity and practical utility can be evaluated by reconstructing or making explicit the underlying causal structure. I will therefore propose to distinguish the alternative definitions according to the kinds of causal content they (...) carry: definitions grounded on associations, definitions presupposing a causal model built upon statistical associations, and definitions grounded on underlying mechanisms. I suggest that analysing definitions according to their causal content can be helpful in evaluating alternative definitions of some diseases. I want to show how the controversy over MetS suggests a distinction among three kinds of definitions based on how explicitly they characterise the syndrome in causal terms, and on the type of causality involved. I will call ‘type 1 definitions’ those definitions that are purely associative; ‘type 2 definitions’ the definitions based on statistical associations, plus generic medical and causal knowledge; and ‘type 3 definitions’ the definitions based on mechanisms. These kinds of definitions, although different, can be related to each other. A definition with more specific causal content may be useful in the evaluation of definitions characterised by a lower degree of causal specificity. Moreover, the identification of the type of causality involved is of help to constitute a good criterion for choosing among different definitions of a pathological entity. In section I introduce the controversy about MetS, in section I propose some remarks about medical definitions and their ‘causal import’, and in section I suggest that the different attitudes towards the definition of MetS are relevant to evaluate their explicative power. (shrink)

Plasminogen activator inhibitor‐1 (PAI‐1) is a physiological inhibitor of urokinase (uPA), a serine protease known to promote cell migration and invasion. Intuitively, increased levels of PAI‐1 should be beneficial in downregulating uPA activity, particularly in cancer. By contrast, in vivo, increased levels of PAI‐1 are associated with a poor prognosis in breast cancer. This phenomenon is termed the “PAI‐1 paradox”. Many factors are responsible for the upregulation of PAI‐1 in the tumor microenvironment. We hypothesize that there is a breast cancer (...) predisposition to a more aggressive stage when PAI‐1 is upregulated as a consequence of Metabolic Syndrome (MetS). MetS exerts a detrimental effect on the breast tumor microenvironment that supports cancer invasion. People with MetS have an increased risk of coronary heart disease, stroke, peripheral vascular disease and hyperinsulinemia. Recently, MetS has also been identified as a risk factor for breast cancer. We hypothesize the existence of the “PAI‐1 cycle”. Sustained by MetS, adipocytokines alter PAI‐1 expression to promote angiogenesis, tumor‐cell migration and procoagulant microparticle formation from endothelial cells, which generates thrombin and further propagates PAI‐1 synthesis. All of these factors culminate in a chemotherapy‐resistant breast tumor microenvironment. The PAI‐1 cycle may partly explain the PAI‐1 paradox. In this hypothesis paper, we will discuss further how MetS upregulates PAI‐1 and how an increased level of PAI‐1 can be linked to a poor prognosis. BioEssays 29:1029–1038, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

ABSTRACT16p11.2 deletion syndrome is a severe genetic disorder associated with the deletion of 27 genes from a Copy Number Variant region on human chromosome 16. Symptoms associated include cognitive impairment, language and motor delay, epilepsy or seizures, psychiatric disorders, autism spectrum disorder (ASD), changes in head size and body weight, and dysmorphic features, with a crucial need to define genes and mechanisms responsible for symptomatology. In this review, we analyze the clinical associations and biological pathways of 16p11.2 locus genes (...) and identify that a majority of 16p11.2 genes relate to metabolic processes. We present a hypothesis in which changes in the dosage of 16p11.2 metabolic genes contribute to pathology through direct or indirect alterations in pathways that include amino acids or proteins, DNA, RNA, catabolism, lipid, energy (carbohydrate). This hypothesis suggests that research into the specific roles of each metabolic gene will help identify useful therapeutic targets. (shrink)

Adipose tissue (AT) inflammation, a hallmark of the metabolic syndrome, is triggered by overburdened adipocytes sending out immune cell recruitment signals during obesity development. An AT immune landscape persistent throughout weight loss and regain constitutes an immune‐obesogenic memory that hinders long‐term weight loss management. Lipid‐associated macrophages (LAMs) are emerging as major players in diseased, inflamed metabolic tissues and may be key contributors to an obesogenic memory in AT. Our previous study found that LAM abundance increases with weight (...) loss via intermittent fasting (IF) in obese mice, which is driven by adipocyte p53 signalling. However, the specific signals causing LAM accumulation in AT under IF remain unknown. In this piece, we hypothesise on a range of adipocyte‐secreted signals that can harbor immune‐attractive features upon fasting/refeeding cycles. We highlight possible mechanisms including cell death signalling, matrikines, and other damage‐associated molecular patterns (DAMPs), as well as adipo(‐cyto)kines, lipid mediators, metabolites, extracellular vesicles, and epigenetic rewiring. Finally, we consider how advances in mechanisms of AT LAM recruitment gleaned from preclinical models might be translatable to long‐term weight management in humans. Thus, we provide vantage points to study signals driving monocyte recruitment, polarisation towards LAMs, and LAM retention, to harness the therapeutic potential of modulating AT LAM levels by impacting the immune‐obesogenic memory in metabolic disease. (shrink)

Dysregulation of lipid metabolism is a commonly observed feature associated with metabolic syndrome and leads to the development of negative health outcomes such as obesity, diabetes mellitus, non‐alcoholic fatty liver disease, or atherosclerosis. Time‐restricted feeding/eating (TRF/TRE), an emerging dietary intervention, has been shown to promote pleiotropic health benefits including the alteration of diurnal expression of genes associated with lipid metabolism, as well as levels of lipid species. Although TRF likely induces a response in multiple organs leading to the (...) modulation of lipid metabolism, a majority of the studies related to TRF effects on lipids have focused only on individual tissues, and furthermore there is a lack of insight into potential underlying mechanisms. In this review, we summarize the current insights regarding TRF effects on lipid metabolism and the potential mechanisms in adipose tissue, liver, skeletal muscle, and heart, and conclude by outlining possible avenues for future exploration. (shrink)

Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin‐converting enzyme (ACE) is the central component of endocrine and local tissue renin–angiotensin systems (RAS), which also regulate diverse aspects of whole‐body metabolism and mitochondrial function (partly through altering mitochondrial UCP expression). We show that ACE expression also appears to be regulated by mitochondrial UCPs. In genetic analysis of two unrelated populations (healthy young UK men and Scandinavian diabetic patients) serum ACE (sACE) activity was significantly higher amongst UCP3‐55C (rather than (...) T) and UCP2 I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold (P < 0·01) whilst increasing ACE expression within a physiological range (<1·8‐fold at 48 h; P < 0·01). Our findings suggest novel hypotheses. Firstly, cellular feedback regulation may occur between UCPs and ACE. Secondly, cellular UCP regulation of sACE suggests a novel means of crosstalk between (and mutual regulation of) cellular and endocrine metabolism. This might partly explain the reduced risk of developing diabetes and metabolic syndrome with RAS antagonists and offer insight into the origins of cardiovascular disease in which UCPs and ACE both play a role. (shrink)

BackgroundPositive psychosocial factors can play an important role in the development of cardiovascular disease. Among them, psychological resilience is defined as the capacity of responding positively to stressful events. Our aim was to assess whether PR is associated with CVD or metabolic disturbances through a systematic review.MethodsWe gathered articles from PubMed, Web of Science, PsycInfo, and Google Scholar up to October 28, 2021. We included articles that were in English, were observational, and had PR examined as exposure. The CVD (...) outcomes were either clinical or metabolic outcomes.ResultsOur literature search identified 3,800 studies, of which 17 met the inclusion criteria. Of them, seven were longitudinal and 10 cross-sectional, and 13 were on adults and four on children. The exposure assessment was heterogeneous, i.e., 12 studies used different kinds of self-administered questionnaires and five used interviews with a psychologist. Regarding outcomes, five studies investigated CVD, seven obesity, one metabolic syndrome, two hypertension, four dyslipidemia, and four diabetes. In longitudinal studies, PR was found to have an inverse association with included outcomes in five studies from the Swedish military conscription cohort but had no association with CVD in a study on African-American women and was associated with slower progression of diabetes in a general population. The cross-sectional studies showed that the prevalence of disease was not associated with PR in many cases but the progression of disease was associated with PR.ConclusionPR seems to have a possibly favorable association with CVD and metabolic disturbances that differs according to the type of outcome and population. Our study limitations are given by the small number of studies available and the heterogeneity in PR measurement.Systematic Review Registration[https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=237109], identifier [CRD42021237109]. (shrink)

It is hypothesized that repeated, non‐invasive stimulation of the vestibular (balance) system, via a small electrical current to the skin behind the ears, will cause the brain centers that control energy homeostasis to shift the body toward a leaner physique. This is because these centers integrate multiple inputs to, in effect, fix a set‐point for body fat, which though difficult to alter is not immutable. They will interpret repeated stimulation of the parts of the vestibular system that detect acceleration as (...) a state of chronic activity. During such a physiologically challenging time it is preferable, from an energy homeostasis viewpoint, to both utilize fat reserves, and reduce the volume of these reserves and thus the energy cost of carrying them around. Hence, this type of vestibular stimulation could potentially be a therapeutic option for metabolic syndrome disorders such as obesity. This hypothesis is eminently testable via a clinical trial. (shrink)

This paper investigates the gendered and racialized discourse on Polycystic Ovary Syndrome in India. A complex metabolic, endocrinal and reproductive disorder, PCOS is one of the most common endocrinopathies in women of reproductive age today. Due to an unclear etiology, there is no single clinical definition for PCOS, contributing to a sense of confusion around the syndrome. India has one of the highest rates of PCOS in the world. Medical and social discourses on PCOS suggest the high (...) rates are due to the failures of Westernized lifestyle and diet in women from developing countries. Taking the example of India, I argue that the lack of a clear etiology creates a discursive vacuum and that PCOS in itself is not a gendered and racialized syndrome, but the discourse on it is. Through the figure of the “new Indian woman,” I address the socio-political anxieties of nationalism projected onto the female body and suggest that the discourse on PCOS in India is in reaction to a rising nationalist rhetoric. As a syndrome that presents through “masculine” symptoms, PCOS acts a unique entryway into the intersectional issues of gender, race, sexuality, class and national identities. An analysis of the Indian setting might shed light on PCOS discourses that are increasingly relevant globally. (shrink)

Metabolic Syndrome is a cluster of risk factors (including obesity, hypertension and insulin resistance), which is associated with late‐onset diabetes and coronary heart disease. Elevated levels of the protease inhibitor PAI‐1 are well‐known molecular markers of the Metabolic Syndrome. Here, however, we present a hypothesis that PAI‐1 acts as a causative factor in the development of Metabolic Syndrome and its clinical sequelae. We propose that PAI‐1 inhibits the activity of members of the proprotein convertase (...) (PC) class of serine proteases and that this underlies, at a molecular level, many of the other features of the Metabolic Syndrome cluster. BioEssays 28: 629–641, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Alterations in the gut microbiome have increasingly been implicated in driving obesity and its associated diseases, but underlying mechanisms remain poorly defined. Herein, in addition to reviewing the field, we hypothesize that a highly significant causative factor of such inflammatory disease‐associated microbiome alterations is a more aggressive microbiota that encroaches upon its host, with components having high potential to activate host pro‐inflammatory gene expression in a manner that drives metabolic disease. We further hypothesize that a range of societal changes, (...) including use of antibiotics and increasing consumption of food additives, have provoked such microbiota aggression and, consequently, may be contributing factors to the increased incidence of obesity and its associated diseases. (shrink)

The prevalence of overweight and obesity in young adults has increased dramatically in recent decades. The unhealthy eating habits that develop at this time can often lead to negative health consequences in the future. It is therefore important to learn about self-regulation and self-control strategies and help young adults to have healthy eating behaviours. This study aims to present an Italian version of the Tempest Self-Regulation Questionnaire for Eating adapted for young adults. The instrument assesses self-regulation and self-control strategies to (...) counteract the desire and temptation to eat unhealthy food and to choose healthy foods. A total of 645 students took part in the study. The results of the confirmatory factor analysis supported the six first-order factors model concerning specific self-regulation strategies and a higher-order structure of the TESQ-E [χ2 = 336.480, p < 0.001; CFI = 0.95; RMSEA = 0.04; SRMR = 0.04]: three correlated second-order factors and one-third-order factor. The results also confirmed the strong measurement invariance of the TESQ-E across gender. To have reliable comparisons across males and females, the latent mean differences tests were performed on the six specific self-regulation strategies. The analysis showed that females appear to prefer strategies that directly address the goal by expressing explicit intentions or plans to eat in a healthy way. Convergence validity was tested through correlations with Eating-Self-Efficacy Brief Scale, Emotional Eating Scale, Scale of Attitudes towards Healthy Eating, and Body Mass Index. In conclusion, the TESQ-E appears to be a psychometrically sound questionnaire that can be effectively used with young adults to measure self-regulation strategies in eating in order to plan personalised interventions for the prevention and control of the metabolic syndrome, and to reduce a wide range of diet-related diseases. (shrink)

Obesity is characterized by the accumulation of an excessive amount of fat mass in the adipose tissue, subcutaneous, or inside certain organs. The risk does not lie so much in the amount of fat accumulated as in its distribution. Abdominal obesity is an important risk factor for cardiovascular diseases, diabetes, and cancer, having an important role in the so-called metabolic syndrome. Therefore, it is necessary to prevent, detect, and appropriately treat obesity. The diagnosis is based on anthropometric indices (...) that have been associated with adiposity and its distribution. Indices themselves, or a combination of some of them, conform to a big picture with different values to establish risk. Anthropometric indices can be used for risk identification, intervention, or impact evaluation on nutritional status or health; therefore, they will be called anthropometric health indicators. We have found 17 AHIs that can be obtained or estimated from 3D human shapes, being a noninvasive alternative compared to X-ray-based systems, and more accessible than high-cost equipment. A literature review has been conducted to analyze the following information for each indicator: definition; main calculation or obtaining methods used; health aspects associated with the indicator ; criteria to classify the population by means of percentiles or cutoff points, and based on variables such as sex, age, ethnicity, or geographic area, and limitations. (shrink)

It is increasingly clear that children's excessive consumption of products high in added (or extrinsic) sugar causes obesity and obesity‐related health problems like type 2 diabetes, cardiovascular disease, and metabolic syndrome. Less clear is how best to address this problem through public health policy. In contrast to policies that might conflict with adult's right to self‐determination — for example sugar taxes and soda bans — this article proposes that children's access to products high in added sugars should be (...) restricted in the same way that children's access to tobacco products is restricted. The article first considers how the recommended policy will protect a child's right to an open future while not violating parental rights. The article then explores how the implementation of the recommended policy can help transform the social meaning of sugar and thereby curb the parental supply of added sugar to children — a central cause of obesity. The article also addresses several potential objections. (shrink)

The practice of physical activity (PA) contributes to the prevention of chronic diseases such as obesity, metabolic syndrome or cardiovascular diseases, being also directly related to the individual’s physical fitness. Therefore, it is necessary to measure and monitoring the levels of PA in childhood and adolescence, since it may be useful to describe their current health status and the association with physical fitness, as well as to reveal putative consequences in the future. Within the educational field, it has (...) been shown that physical education (PE) classes are a favorable context for the creation of healthy physical-sports habits and self-determined motivation could be a key for explaining the level of PA practice. For this reason, the purpose of this research was to study the mediating role of integrated regulation (IR) on the relationship between PA and physical fitness in children and adolescents. A total of 325 students between 11 and 14 years old participated in the study. The level of PA was estimated through the specific Physical Activity Questionnaire for Children (PAQ-C), while motivation and IR were measured by using the Perceived Locus of Causality scale (PLOC-2). In addition, physical fitness was measured through the Eurofit fitness battery of tests, composed of three body composition measures and seven tests of different physical capacities. The physical fitness score showed no differences when genders were compared. After regression analysis, the resulti... (shrink)

Mitochondrial homeostasis serves as a cornerstone of cellular function, orchestrating a delicate balance between energy production, redox status, and cellular signaling transduction. This equilibrium involves a myriad of interconnected processes, including mitochondrial dynamics, quality control mechanisms, and biogenesis and degradation. Perturbations in mitochondrial homeostasis have been implicated in a wide range of diseases, including neurodegenerative diseases, metabolic syndromes, and aging‐related disorders. In the past decades, the discovery of numerous mitochondrial proteins and signaling has led to a more complete understanding (...) of the intricate mechanisms underlying mitochondrial homeostasis. Recent studies have revealed that Family with sequence similarity 210 member A (FAM210A) is a novel nuclear‐encoded mitochondrial protein involved in multiple aspects of mitochondrial homeostasis, including mitochondrial quality control, dynamics, cristae remodeling, metabolism, and proteostasis. Here, we review the function and physiological role of FAM210A in cellular and organismal health. This review discusses how FAM210A acts as a regulator on mitochondrial inner membrane to coordinate mitochondrial dynamics and metabolism. (shrink)

New C. elegans studies imply that lipases and lipid desaturases can mediate signaling effects on aging. But why might fat homeostasis be critical to aging? Could problems with fat handling compromise health in nematodes as they do in mammals? The study of signaling pathways that control longevity could provide the key to one of the great unsolved mysteries of biology: the mechanism of aging. But as our view of the regulatory pathways that control aging grows ever clearer, the nature of (...) aging itself has, if anything, grown more obscure. In particular, focused investigations of the oxidative damage theory have raised questions about an old assumption: that a fundamental cause of aging is accumulation of molecular damage. Could fat dyshomeostasis instead be critical? (shrink)

The mutations that cause many forms of inherited retinal degenerations have been identified, yet the mechanisms by which these mutations lead to death of photoreceptor cells of the retina are not completely understood. Investigations of the pathways from mutation to retinal degeneration have focused on spontaneous and engineered animal models of disease. Based on the studies performed to date, four major categories of degeneration mechanism can be identified. These include disruption of photoreceptor outer segment morphogenesis, metabolic overload, dysfunction of (...) retinal pigment epithelial cells, and chronic activation of phototransduction. Future investigations will likely identify additional mechanisms of photoreceptor damage. This review will summarize what has been learned from studying animal models of non-syndromic inherited retinal degenerations. BioEssays 23:605–618, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Objectives: Recent fMRI studies have shown that it is possible to reliably identify the defaultmode network (DMN) in the absence of any task, by resting-state connectivity analyses in healthy volunteers. We here aimed to identify the DMN in the challenging patient population of disorders of consciousness encountered following coma. Experimental design: A spatial independent component analysis-based methodology permitted DMN assessment, decomposing connectivity in all its different sources either neuronal or artifactual. Three different selection criteria were introduced assessing anticorrelation-corrected connectivity with (...) or without an automatic masking procedure and calculating connectivity scores encompassing both spatial and temporal properties. These three methods were validated on 10 healthy controls and applied to an independent group of 8 healthy controls and 11 severely brain-damaged patients [locked-in syndrome (n ¼ 2), minimally conscious (n ¼ 1), and vegetative state (n ¼ 8)]. Principal observations: All vegetative patients showed fewer connections in the default-mode areas, when compared with controls, contrary to locked-in patients who showed nearnormal connectivity. In the minimally conscious-state patient, only the two selection criteria considering both spatial and temporal properties were able to identify an intact right lateralized BOLD connectivity pattern, and metabolic PET data suggested its neuronal origin. Conclusions: When assess-. (shrink)

Recent experimental evidence suggests that most of the genome is transcribed into non‐coding RNAs. The initial transcripts undergo further processing generating shorter, metabolically stable RNAs with diverse functions. Small nucleolar RNAs (snoRNAs) are non‐coding RNAs that modify rRNAs, tRNAs, and snRNAs that were considered stable. We review evidence that snoRNAs undergo further processing. High‐throughput sequencing and RNase protection experiments showed widespread expression of snoRNA fragments, known as snoRNA‐derived RNAs (sdRNAs). Some sdRNAs resemble miRNAs, these can associate with argonaute proteins and (...) influence translation. Other sdRNAs are longer, form complexes with hnRNPs and influence gene expression. C/D box snoRNA fragmentation patterns are conserved across multiple cell types, suggesting a processing event, rather than degradation. The loss of expression from genetic loci that generate canonical snoRNAs and processed snoRNAs results in diseases, such as Prader‐Willi Syndrome, indicating possible physiological roles for processed snoRNAs. We propose that processed snoRNAs acquire new roles in gene expression and represent a new class of regulatory RNAs distinct from canonical snoRNAs.Also watch the Video Abstract. (shrink)

The prevention of disability has been the driving force behind much research. In epidemiology three levels of prevention are defined: primary, secondary, and tertiary prevention. Primary prevention is the prevention of the initiation or occurrence of a disease; secondary prevention is the prevention or amelioration of the consequences of a disease, and tertiary prevention refers to rehabilitation or the limitation of disability associated with the disease. We have examples of all three levels of prevention in the area of childhood disability. (...) Primary prevention is the protection of infants against congenital rubella syndrome by ensuring that women of childbearing age have adequate immunity before they become pregnant. The prevention of choreoathetosis, mental retardation, and deafness, by treating hyperbilirubinemia and preventing kernicterus in newborns, is a great success story in prevention. Similarly, at the level of secondary prevention, is the reduction in mental retardation caused by phenylketonuria, or PKU, by eliminating phenylalanine in the diets of newborns who lack the enzyme to metabolize this amino acid. Tertiary prevention is the area of rehabilitation medicine, and is regarded as the least desirable level of prevention. Indeed, tertiary prevention can be seen as “doing the best we can” in terms of rehabilitation, often while seeking a means of really preventing the disease. (shrink)

This book provides a detailed account of intellectual, other neuropsychological and behavioral manifestations of general pediatric diseases. The conditions discussed include the whole range of pediatric diseases - genetic syndromes, other congenital conditions, metabolic, endocrine, gastrointestinal, infectious, immunologic, toxic, trauma, and neoplastic, as well as sensory disabilities including deafness and blindness. Although the book is not intended to discuss cognitive and behavioral manifestations of conditions usually considered to be primary neurological disease, some of those, including cerebral palsy, muscular dystrophy, (...) myotonic dystrophy and epilepsy, are included.Where possible, a. (shrink)

Human UDP‐glucuronosyltransferases (UDPGTs) are a family of enzymes which detoxify many hundreds of compounds by their conjugation to glucuronic acid, rendering them both harmless and more water soluble, hence, excretable. The level of expression of each UDPGT isoform in the body is the result of interplay between temporal, tissue‐specific and environmental regulators. This complexity contributes to the difficulty in predicting the metabolic fate of compounds.Genetic defects and polymorphisms affecting individual isoform activities have deleterious and potentially lethal effects, as exemplified (...) by the severe hyperbilirubinaemia observed in Crigler‐Najjar Syndrome. Such severe genetic defects in bilirubin glucuronidation are obvious candidates for antenatal screening and gene therapy. (shrink)

Obesity and type 2 diabetes arise from a set of complex gene–environment interactions. Explanations for the heritability of these syndromes and the environmental contribution to disease susceptibility are addressed by the “thrifty genotype” and the “thrifty phenotype” hypotheses. Here, the merits of both models are discussed and elements of them are used to synthesize a “thrifty epigenotype” hypothesis. I propose that: (1) metabolic thrift, the capacity for efficient acquisition, storage and use of energy, is an ancient, complex trait, (2) (...) the environmentally responsive gene network encoding this trait is subject to genetic canalization and thereby has become robust against mutational perturbations, (3) DNA sequence polymorphisms play a minor role in the aetiology of obesity and type 2 diabetes—instead, disease susceptibility is predominantly determined by epigenetic variations, (4) corresponding epigenotypes have the potential to be inherited across generations, and (5) Leptin is a candidate gene for the acquisition of a thrifty epigenotype. BioEssays 30:156–166, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Cognition in living entities—and their social groupings or institutional artifacts—is necessarily as complicated as their embedding environments, which, for humans, includes a particularly rich cultural milieu. The asymptotic limit theorems of information and control theories permit construction of a new class of empirical ‘regression-like’ statistical models for cognitive developmental processes, their dynamics, and modes of dysfunction. Such models may, as have their simpler analogs, prove useful in the study and re-mediation of cognitive failure at and across the scales and levels (...) of organization that constitute and drive the phenomena of life. These new models particularly focus on the roles of sociocultural environment and stress, in a large sense, as both trigger for the failure of the regulation of bio-cognition and as ‘riverbanks’ determining the channels of pathology, with implications across life-course developmental trajectories. We examine the effects of an embedding cultural milieu and its socioeconomic implementations using the ‘lenses’ of metabolic optimization, control system theory, and an extension of symmetry-breaking appropriate to information systems. A central implication is that most, if not all, human developmental disorders are fundamentally culture-bound syndromes. This has deep implications for both individual treatment and public health policy. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Philosophy, Psychiatry, & Psychology 10.1 (2003) 63-66 [Access article in PDF] The Pragmatics of Psychiatry and the Psychiatry of Cross-Cultural Suffering Jennifer Radden I AM IN SUBSTANTIAL AGREEMENT with many of the conclusions David Brendel draws in his thoughtful discussion. Misleading language aside, I particularly applaud his use of my plea for ontological descriptivism to support clinical practice, which respects, as he puts it, the subjectively "melancholic" person living (...) behind the objectively "depressed" clinical presentation.Brendel offers two main critiques of my discussion about the relationship between today's depression and melancholia of past eras. First, he asserts that I neglect the relevance of causal reasoning in my preference for a descriptivist over a causal ontology. Second, arguing that pragmatic considerations ought to be, as he says, front and center when philosophers and psychiatrists "grapple with the complexities of psychiatric explanation," (Brendel 2003, 54) he questions what he sees as my too ready dismissal of pragmatism in this discussion. Allegiance to pragmatism seems to me to sit strangely with support for a causal ontology, as I shall try to demonstrate. But first let me comment on these two sides of Brendel's commentary.The case of Van Gogh's alleged melancholia is particularly well chosen because there has been continuing debate about Van Gogh's condition, including scholarly work attributing it to an inherited metabolic disorder (Arnold 1992). Brendel's suggestion that a causal ontology might allow us to use historical evidence to throw light on the relation between depression and melancholia is an interesting and fruitful one that I had overlooked. Brendel also holds hope for drug cartography as a means of determining the causes of mental disorders. I admit to the initial plausibility of the approach to classification employed by drug cartography, of course. Diagnostic maps must be evaluated according to their effectiveness for the purposes they serve, and cannot—or should not—be seen as mere descriptions of natural phenomena. And maps based on psychopharmacological effects will serve one of the most important purposes we can have in relation to mental disorders: their successful treatment. Nonetheless, as I indicated in my essay, there are conceptual limitations to drug cartography. That several different syndromes respond to the same drug is suggestive, but it does not tell us anything definitive about structural similarities or differences between those different disorders. Nor, from the fact that a condition is alleviated by drugs, does it follow that a particular brain state was the initiating cause of that condition.My dismissal of a pragmatic approach in the foregoing discussion may have been overly hasty. [End Page 63] But in trying to make good this omission, I find myself struck by the complexity of the task. There appear to be at least five different places where a pragmatic response might be called for: (1) in deciding what to say about the relationship between depression and melancholia; (2) in determining the structure of any given psychiatric classification; (3) in choosing between what I have called descriptivist and causal ontologies; (4) in electing a course or method of treatment in the clinical context; and (5) in evaluating psychiatric explanations.With regard to (1), I have sketched in a note one pragmatic consideration in favor of equating melancholia and depression: by so doing, we might reinvest depressive states with some of the glamorous associations from the past and so diminish the stigma and provide some compensation and consolation for the suffering attaching to depression. Pragmatic reasoning may be perfectly appropriate here. I beg to point out that pragmatic considerations let me neglect it.With regard to (2), I recognize that psychiatric classifications are not so much identifications of natural kinds as responses to our various purposes; indeed, this point is offered as one drawback of adopting a causal analysis, because there is little reason to expect our purposes, which are a product of culture, to correspond to natural arrangements, which are not.With regard to (3), if there were overriding pragmatic considerations that favored accepting one or the other of these ontologies, then perhaps this would be... (shrink)

Genetics offers real opportunities for public health actors. Increased understanding of genetics will illuminate some of the factors that affect disease and, in many cases, will lead to more effective treatments. The recognition that phenylketonuria was caused by a metabolic defect that led to the accumulation of toxic levels of phenylalanine, an elevation that could largely be averted by adopting a low-phenylalanine diet, is an early example. Some cases of what was thought to be Sudden Infant Death Syndrome, (...) a diagnosis used when no etiology is known, now appear to have been caused by metabolic defects in fatty acid oxidation and sodium channel defects. One of the tasks that has already been undertaken by the public health sector is to ensure that genomic information is incorporated into clinical care when the robusmess of findings and their clinical utility have been well defined. (shrink)

Can we identify potential long-term consequences of digitalisation on public health? Environmental studies, metabolic research, and state of the art research in neurobiology point towards the reduced amount of natural day and sunlight exposure of the developing child, as a consequence of increasingly long hours spent indoors online, as the single unifying source of a whole set of health risks identified worldwide, as is made clear in this review of currently available literature. Over exposure to digital environments, from abuse (...) to addiction, now concerns even the youngest (ages 0 to 2) and triggers, as argued on the basis of clear examples herein, a chain of interdependent negative and potentially long-term metabolic changes. This leads to a deregulation of the serotonin and dopamine neurotransmitter pathways in the developing brain, currently associated with online activity abuse and/or internet addiction, and akin to that found in severe substance abuse syndromes. A general functional working model is proposed under the light of evidence brought to the forefront in this review. (shrink)

It may seem trivial to state that one of the major trends in biological investigation consists in an attempt to explain the structural and functional aspects of living matter in chemical terms, in an effort to obtain insight into the equivalent of macroscopic phenomena on the molecular level. I am sure you are aware of, and this meeting of the Association has brought ample additional evidence, in how many fields this tendency has become apparent. It can be recognized in genetics (...) with the molecular analysis of chromosomes and the enzymatic or metabolic interpretation of hereditary properties like the eyecolor of Drosophila. In a purely morphological branch like histology we do not ask merely for a differentiation of stained cell structure but we ask for the nature of the staining reaction; in nerve physiology we try to interpret conduction as alterations of protein lipoid layers; or in pathology where the age old syndrome of inflammation is explored with biochemical methods. I should mention molecular models of membranes and cell surfaces, the molecular interpretation of secretion and of the macroscopic phenomena of metabolism. Yet insofar as this yield of data could be designated as a trend, it would rather seem to be the natural outcome to be expected from the application of the analytic method of science. In one instance, however, this approach has been carried farther than in all the other fields, and it would seem to be worthwhile to pause for one moment to ask whether this case is important merely because of its technical implications or whether it is meaningful in a wider sense. (shrink)

Variations in life history define key comparative and evolutionary biological questions, important for understanding the mechanisms of mammalian evolutionary divergence, developmental adaptability and plasticity. In this regard, the differences among predominantly altricial and precocial species represent a particularly significant, if still poorly understood and contested case. Here, it will be shown how the classical analysis of such ontogenetic variations, going back to the semantic biology of A. Portmann, can be expanded and synthesized with comparative physiological approaches, based on the negentropic (...) theory of ontogeny by I. A. Arshavsky and his school. In this little received but pioneering tradition, extensive comparative and experimental investigations were carried out on the role of musculoskeletal systems and stressors in driving life history variations, particularly in the altricial-precocial spectrum. As shown by Arshavsky and co-workers, by focusing on general allometric regularities, the approximations based on the classical energy rules of surface and mass offer valuable benchmarks, but also predictions that are frequently violated by the variability of physiological and metabolic scaling relationships among altricials and precocials, and thus, a complex and historical approach is needed to describe their local physiological mechanisms and systemic regularities. This paper shows how Arshavsky’s findings and framework can play an integrative role in this context, potentially helping to bridge the mainly descriptive approach of semantic morphology, as developed by Portmann’s school, with the more functional explanations predominating current ecology and life history theory. These problems can be important for biosemiotics by highlighting the contingent, activity-dependent, and surplus anabolic stress mechanisms underlying diversification in eutherian developmental systems and possibly, the epigenetic evolution of pace-of-life syndromes. (shrink)

When an agent can not recognize, immediately, the implausible part of new information received, she will usually first expand her belief state by the new information, and then she may encounter some belief conflicts, and find the implausible information based on her criteria to consolidate her belief state. This process indicates a new kind of non-prioritized multiple revision, called metabolic revision. I give some axiomatic postulates for metabolic revision and propose two functional constructions for it, namely kernel (...) class='Hi'>metabolic revision and partial meet metabolic revision, with respect to which the representation theorems are proved. I also compare metabolic revision with some related works in the literature, including semi-revision, merging with integrity constraints, evaluation, and evaluative multiple revision. (shrink)

Williams syndrome is a genetic disorder that, because of its unique cognitive profile, has been marshalled as evidence for the modularity of both language and social skills. But emerging evidence suggests the claims of modularity based on WS have been premature. This paper offers an examination of the recent literature on WS. It argues the literature gives little support for mental modularity. Rather than being rigidly modular, the WS brain is an extremely flexible organ that that co-opts available neural (...) resource in a highly dynamic manner to cope in the world. (shrink)

Various lipid transfer proteins (LTPs) mediate the inter‐organelle transport of lipids. By working at membrane contact zones between donor and acceptor organelles, LTPs achieve rapid and accurate inter‐organelle transfer of lipids. This article will describe the emerging paradigm that the action of LTPs at organelle contact zones generates metabolic channeling events in lipid metabolism, mainly referring to how ceramide synthesized in the endoplasmic reticulum is preferentially metabolized to sphingomyelin in the distal Golgi region, how cholesterol and phospholipids receive specific (...) metabolic reactions in mitochondria, and how the hijacking of host LTPs by intracellular pathogens may generate new channeling‐like events. In addition, the article will discuss how the function of LTPs is regulated, exemplified by a few representative LTP systems, and will briefly touch on experiments that will be necessary to establish the paradigm that LTP‐mediated inter‐organelle transport of lipids is one of the mechanisms of compartmentalization‐based metabolic channeling events. (shrink)

The research sought to determine the prevalence of Burnout Syndrome in health teachers at a university in north-eastern Peru. The universe was made up of 69 teachers, and 41 responded to the self-administered instrument called Maslach Burnout Inventory. The results show that 14.6% present this syndrome. The highest indicator was personal fulfillment, while depersonalization and emotional exhaustion were low. According to gender, in both it was similar. According to age group, it had a greater effect in ages between (...) 36 and 51 years. Marital status was more prevalent in singles. We conclude that the prevalence of Burnout Syndrome was low. (shrink)

The reprogramming of metabolism has been identified as one of the hallmarks of cancer. It is becoming more and more frequent to connect other diseases with metabolic reprogramming. This article aims to argue that metabolic reprogramming is not driven by disease but instead is the main hallmark of metabolism, based on its dynamic behavior that allows it to continuously adapt to changes in the internal and external conditions.

Many intelligent, capable, and successful individuals believe that their success is due to luck and fear that they will someday be exposed as imposters. A puzzling feature of this phenomenon, commonly referred to as imposter syndrome, is that these same individuals treat evidence in ways that maintain their false beliefs and debilitating fears: they ignore and misattribute evidence of their own abilities, while readily accepting evidence in favour of their inadequacy. I propose a novel account of imposter syndrome (...) as an instance of self-deception, whereby biased evidence treatment is driven by the motivational benefit of negative self-appraisal. This account illuminates a number of interconnected philosophical and scientific puzzles related to the explanation, definition, and value of imposter syndrome. (shrink)

Le syndrome de Kierkegaard est un essai libre de Jean- Luc Berlet, consacré à l'un de ses penseurs de prédilection, le Danois Seren Kierkegaard (1813-1855). Ce syndrome dont il est question, tel que défini par l'auteur, pourrait être conçu comme la tension qui résulte de l'impossible choix entre l'amour de la femme et l'amour de Dieu. Kierkegaard renonça en effet à l'amour charnel de la femme au profit d'une vie ascétique consacrée à I écriture et à la réflexion (...) sur l'Amour. A plus grande échelle ce syndrome pourrait être compris comme l'abandon du temporel au profit d'un idéal spirituel Et les regrets qui en découlent. En effet, comme nombre de contemporains opérant ce type de choix, Kierkegaard connut bien des tourments. Ces affres permirent néanmoins à Kierkegaard de développer une conception de l'Amour et du Divin d'une grande originalité qu'il est bon de redécouvrir dans notre époque marquée par le consumérisme sentimental. Tout au long des quatorze chapitres qui jalonnent cet ouvrage, Jean-Luc Berlet retrace le parcours littéraire de ce philosophe danois considéré par beaucoup comme le père de l'existentialisme, brossant ici un tableau complet de son énigmatique personnalité. En outre, chaque chapitre est accompagné d'un code QR, donnant chacun actes à une vidéo en ligne où Jean - Luc Berlet approfondit son développement et fournit des clefs de lecture pour une meilleure compréhension de l'oeuvre de Kierkegaard. (shrink)

Metabolic systems are complicated and contain very large numbers of interacting reactions and many internal regulatory mechanisms. This does not prevent the genetic composition of an organism from influencing its behavior, however, nor does it preclude the possibility that some aspects of its behavior may be amenable to simple explanations.

Many kinds of multifunctional regulatory proteins have been identified that perform distinct biochemical functions in the nucleus, the cytoplasm, or both. Here we describe the recent discovery by Hall et al. (2004)1 of a new type of multifunctional protein: a metabolic enzyme that doubles as a transcription factor. This enzyme, Arg5,6, functions as a catalytic enzyme in ornithine biosynthesis and also binds and regulates the promoters of nuclear and mitochondrial genes. It may also regulate precursor mRNA metabolism. We discuss (...) how proteins that serve as both metabolic enzymes and transcription factors might have evolved. BioEssays 27:467–471, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Cockayne syndrome is a rare autosomal recessive disease characterized by a complex clinical phenotype. Most Cockayne syndrome cells are hypersensitive to killing by ultraviolet radiation. This observation has prompted a wealth of studies on the DNA repair capacity of Cockayne syndrome cells in vitro. Many studies support the notion that such cells are defective in a DNA repair mode(s) that is transcription‐dependent. However, it remains to be established that this is a primary molecular defect in Cockayne (...) class='Hi'>syndrome cells and that it explains the complex clinical phenotype associated with the disease. An alternative hypothesis is that Cockayne syndrome cells have a defect in transcription affecting the expression of certain genes, which is compatible with embryogenesis but not with normal post‐natal development. Defective transcription may impair the normal processing of DNA damage during transcription‐dependent repair.‘“Curiouser and curiouser” cried Alice.’ (Lewis Carroll, Alice's Adventures in Wonderland). (shrink)

This chapter highlights the complexity of the relationship between enhancement of mood and cognition on the one hand and the improvement of people's well‐being on the other. To do so, two psychiatric conditions, Asperger's syndrome and bipolar disorder, are presented in the chapter. Even though there are both negative and positive aspects to Asperger's syndrome or to bipolar disorders, taking away even these negative aspects would not necessarily promote well‐being. It might also be impossible to isolate the positive (...) aspects of these disorders. An increase in specific forms of cognition might be intrinsically connected to a decrease in specific aspects of mood. A decrease in specific aspects of mood might be intrinsically connected to an increase in creativity. Neither is necessarily linked to any changes in some general form of “well‐being.”. (shrink)

Impostor Syndrome is the belief or feeling that one is passing oneself off as much more capable than one really is. Anecdotally, it is experienced more by members of historically disadvantaged groups, but the empirical data seems inconsistent with this view. I argue that impostor syndrome occurs because (a) it is normal, appropriate and often even necessary to engage in some degree of pretense in order to acquire specialist expertise, but (b) we are much more likely to be (...) aware of our own pretense than that of others. I argue that we are especially likely to notice pretense when we’re made self-conscious, and that failing to match the stereotype of one’s profession or domain of expertise tends to give rise to self-consciousness. Self-consciousness is elicited by certain cues; this fact explains not only the greater vulnerability of the members of some groups to it, but also explains why the empirical data has not yet provided evidence for this greater vulnerability. I end with some suggestions for reducing the prevalence or impact of impostor syndrome. (shrink)

Computational approaches in systems biology have become a powerful tool for understanding the fundamental mechanisms of cellular metabolism and regulation. However, the interplay between the regulatory and the metabolic system is still poorly understood. In particular, there is a need for formal mathematical frameworks that allow analyzing metabolism together with dynamic enzyme resources and regulatory events. Here, we introduce a metabolic-regulatory network model that allows integrating metabolism with transcriptional regulation, macromolecule production and enzyme resources. Using this model, we (...) show that the dynamic interplay between these different cellular processes can be formalized by a hybrid automaton, combining continuous dynamics and discrete control. (shrink)

Syndrom uprzedmiotowienia narodowego Polaków jest systemem hamowania aktywności zbiorowej i jednostkowej. Wytwarzany jest poprzez redukcje instytucjonalnych podstaw samostanowienia obywateli, a pogłębiany z powodu niemożności akumulacji osobistej własności i gospodarowania dobrem wspólnym przez pojedyncze podmioty. Polega tez na blokowaniu personalnej dyspozycji do rozpoznania narzucanych zależności. W okresie transformacji politycznej w Polsce po 1989 roku takie strategie zostały skutecznie zastosowane.