Host defense mechanisms are categorized into different strategies, namely, avoidance, resistance and tolerance. Resistance encompasses mechanisms that directly kill the pathogen while tolerance is mainly concerned with alleviating the harsh consequences of the infection regardless of the pathogen burden. Resistance is well‐known strategy in immunology while tolerance is relatively new. Studies addressed tolerance mainly using mouse models revealing a wide range of interesting tolerance mechanisms. Herein, we aim to emphasize on the interspecies comparative approaches to (...) explore potential new mechanisms of disease tolerance. We will discuss mechanisms of tolerance with focus on those that were revealed using comparative study designs of mammals followed by summarizing the reasons for adopting comparative approaches on disease tolerance studies. Disease tolerance is a relatively new concept in immunology, we believe combining comparative studies with model organism study designs will enhance our understanding to tolerance and unveil new mechanisms of tolerance. (shrink)

“Exercise starts and ends in the brain”: this was the title of a review article authored by Dr. Bengt Kayser back in 2003. In this piece of work, the author highlights that pioneer studies have primarily focused on the cardiorespiratory-muscle axis to set the human limits to whole-body exercise tolerance. In some circumstances, however, exercise cessation may not be solely attributable to these players: the central nervous system is thought to hold a relevant role as the ultimate site of (...) exercise termination. In fact, there has been a growing interest relative to the “brain” response to exercise in chronic cardiorespiratory diseases, and its potential implication in limiting the tolerance to physical exertion in patients. To reach these overarching goals, non-invasive techniques, such as near-infrared spectroscopy and transcranial magnetic stimulation, have been successfully applied to get insights into the underlying mechanisms of exercise limitation in clinical populations. This review provides an up-to-date outline of the rationale for the “brain” as the organ limiting the tolerance to physical exertion in patients with cardiorespiratory diseases. We first outline some key methodological aspects of neuromuscular function and cerebral hemodynamics assessment in response to different exercise paradigms. We then review the most prominent studies, which explored the influence of major cardiorespiratory diseases on these outcomes. After a balanced summary of existing evidence, we finalize by detailing the rationale for investigating the “brain” contribution to exercise limitation in hitherto unexplored cardiorespiratory diseases, an endeavor that might lead to innovative lines of applied physiological research. (shrink)

Background: Freezing of gait is a common symptom in Parkinson’s disease and can be difficult to treat with dopaminergic medications or with deep brain stimulation. Novel stimulation paradigms have been proposed to address suboptimal responses to conventional DBS programming methods. Burst-cycling deep brain stimulation delivers current in various frequencies of bursts, while maintaining an intra-burst frequency identical to conventional DBS.Objective: To evaluate the safety and tolerability of BCDBS in PD patients with FOG.Methods: Ten PD subjects with STN or GPi (...) DBS and complaints of FOG were recruited for this single center, single blinded within-subject crossover study. For each subject, we compared 4, 10, and 15 Hz BCDBS to conventional DBS during the PD medication-OFF state.Results: There were no serious adverse events with BCDBS. It was feasible and straightforward to program BCDBS in the clinic setting. The benefit was comparable to conventional DBS in measures of FOG, functional mobility and in PD motor symptoms. BCDBS had lower battery consumption when compared to conventional DBS.Conclusions: BCDBS was feasible, safe and well tolerated and it has potential to be a viable future DBS programming strategy. (shrink)

I propose a T‐cell receptor (TcR)‐based mechanism by which immunity mediates both “genetic self” and “microbial self” thereby, connecting microbiome disease with autoimmunity. The hypothesis is based on simple principles. First, TcR are selected to avoid strong cross‐reactivity with “self,” resulting in selection for a TcR repertoire mimicking “genetic self.” Second, evolution has selected for a “microbial self” that mimics “genetic self” so as to share tolerance. In consequence, our TcR repertoire also mimics microbiome antigenicity, providing a novel (...) mechanism for modulating tolerance to it. Also, the microbiome mimics the TcR repertoire, acting as a secondary immune system. I call this TcR‐microbiome mimicry “holoimmunity” to denote immune tolerance to the “holobiont self.” Logically, microbiome‐host mimicry means that autoimmunity directed at host antigens will also attack components of the microbiome, and conversely, an immunological attack on the microbiome may cross‐react with host antigens producing “holoautoimmunity.”. (shrink)

The random nature of immunoglobulin gene segment rearrangement inevitably leads to the generation of self‐reactive B cells. Avoidance of destructive autoimmune reactions is necessary in order to maintain physiological homeostasis. However, current central and peripheral tolerance concepts fail to explain the massive number of autoantibody‐borne autoimmune diseases. Moreover, recent studies have shown that in physiological mouse models autoreactive B cells were neither clonally deleted nor kept in an anergic state, but were instead able to mount autoantibody responses. We propose (...) that activation of autoreactive B cells is induced by polyvalent autoantigen complexes that can occur under physiological conditions. Repeated encounter of autoantigen complexes leads to the production of affinity‐matured autoreactive IgM that protects its respective self‐targets from degradation. We refer to this novel mechanism as adaptive tolerance. This article discusses the discovery of adaptive tolerance and the unexpected role of high affinity IgM autoantibodies. (shrink)

Background and aims. In pediatrics receiving a diagnosis of a chronic condition is a matter that involves caregivers at first. Beyond the basic issues of caring for the physical body of the ill child, caregivers’ manners of facing and making sense of the disease orient and co-construct their children’s sensemaking processes of the disease itself. The aim of this article is to explore the experience of a rare chronic illness, Hereditary Angioedema (HAE), in pediatrics, from the caregivers’ perspective. (...) Hereditary Angioedema is characterized by subcutaneous swellings that can involve the mucosal tissues of external as well as internal parts of the body, manifesting in a highly variable and unpredictable way in terms of localization, severity, and frequency. Materials and methods. Within a qualitatively-driven research design, we conducted a qualitative narrative semiotic analysis of n.28 mothers’ narratives on their children’s disease experience. Narratives were collected by an ad hoc interview on three domains of the disease experience: A. interpretation of the disease variability; B. dialogical processes; C. management of the disease. Subsequently, we executed a TwoStep cluster analysis for categorical data to detect cross-sectional profiles of the maternal sensemaking processes of the disease. Results. The coding grid was built analyzing the characteristic of the narrative links that orient the connection between the elements of the experience within each domain: A. the connection among events, for the domain of the interpretation of the disease variability; B. the connection between self and other, for the domain of the dialogue; C. the connection among sensemaking and actions, for the domain of the management of the disease. Results from cluster analysis show three narrative profiles: 1. adempitive; 2. reactive; 3. dynamic. Discussion. Profiles will be discussed in the light of the general conceptual framework of the Sense of Grip on the Disease (SoGoD) highlighting the importance of those sensemaking processes which, instead of relying on a coherent and close interpretation of the disease, are characterized by a degree of tolerance for the uncertainty and the unknowingly. (shrink)

A PROPOSAL FOR DEFINING DISEASE, OFFERED BY HAROLD MERSKEY, M. D., IS EXAMINED. REASONS FOR TOLERATING A LOGICALLY RELAXED SENSE OF DEFINITION ARE PUT FORWARD. MERSKEY'S OWN PROPOSAL IS BASED ON A CANVASS OF A LARGE NUMBER OF CURRENT ATTEMPTS AT DEFINITION.

Differences in perceptions and knowledge of crop diseases constitute a major obstacle in farmer–researcher cooperation, which is necessary for sustainable disease management. Farmers’ perceptions and management of crop diseases in the northern Ethiopian Regional State of Tigrai were investigated in order to harness their knowledge in the participatory development of integrated disease management (IDM) strategies. Knowledge of disease etiology and epidemiology, cultivar resistance, and reasons for the cultivation of susceptible cultivars were investigated in a total of 12 (...) tabias (towns) in ten weredas (districts). Perception of diseases involved both scientific and spiritual conceptual frameworks. Of the more than 30 crop diseases recorded on the major crops in the region, only rusts and powdery mildews (locally called humodia) and a few root rots were considered by farmers to be important. Farmers’ awareness of other diseases was extremely low; some highly damaging but less conspicuous diseases, such as faba bean chocolate spot and chickpea ascochyta blight (also called humodia), were not regarded by farmers as disease but as problems caused primarily by excessive soil moisture. Considering that some of these “unrecognized” diseases can cause complete yield loss and genetic erosion in epiphytotic years, there is an urgent need for bringing together farmers’ and scientists’ knowledge to complement each other. Even when farmers had access to disease-resistant or disease-tolerant cultivars, they grew susceptible local varieties because of multiple criteria including earliness, good yield in years with low humodia severity, suitability for home consumption, market demand/quality, and low soil fertility and land management requirements. Farmer innovation and knowledge were evident in their use of diverse disease control measures, but these were a mixture of the “useful and the useless.” Our findings stress the necessity for extension workers and researchers to understand and improve farmers’ knowledge of crop diseases, and farmers’ ability to observe and experiment, through the Farmer Field School or a similar experiential learning approach. These insights about farmers’ knowledge of crop diseases provide a basis for further collaborative maintenance of crop genetic diversity, development of germplasm, and IPM-related research in Africa. (shrink)

Plants from a handful of species provide the primary source of food for all people, yet this source is vulnerable to multiple stressors, such as disease, drought, and nutrient deficiency. With rapid population growth and climate uncertainty, the need to produce crops that can tolerate or resist plant stressors is more crucial than ever. Traditional plant breeding methods may not be sufficient to overcome this challenge, and methods such as highOthroughput sequencing and automated scoring of phenotypes can provide significant (...) new insights. Ontologies are essential tools for accessing and analysing the large quantities of data that come with these newer methods. As part of a larger project to develop ontologies that describe plant phenotypes and stresses, we are developing a plant disease extension of the Infectious Disease Ontology (IDOPlant). The IDOPlant is envisioned as a reference ontology designed to cover any plant infectious disease. In addition to novel terms for infectious diseases, IDOPlant includes terms imported from other ontologies that describe plants, pathogens, and vectors, the geographic location and ecology of diseases and hosts, and molecular functions and interactions of hosts and pathogens. To encompass this range of data, we are suggesting inOhouse ontology development complemented with reuse of terms from orthogonal ontologies developed as part of the Open Biomedical Ontologies (OBO) Foundry. The study of plant diseases provides an example of how an ontological framework can be used to model complex biological phenomena such as plant disease, and how plant infectious diseases differ from, and are similar to, infectious diseases in other organism. (shrink)

Introduction Outbreaks of serious communicable infectious diseases remain a major global medical problem and force healthcare workers to make hard choices with limited information, resources and time. While information regarding physicians’ opinions about such dilemmas is available, research discussing students’ opinions is more limited. Methods Medical students were surveyed about their willingness to perform medical procedures on patients with communicable diseases as students and as physicians. Students were asked about their opinions regarding the duty to treat in such cases. Results (...) 74% of respondents felt that by deciding to enter medical school they were morally obliged to treat any patient despite the risks. Students’ willingness to treat as physicians is significantly higher than their willingness to treat as students. HIV was significantly the most tolerated disease with respect to performing mouth to mouth resuscitation. Among preclinical students, we found that willingness to treat during the later years is significantly greater than during the earlier years. Among clinical students, the opposite was observed. Discussion Students’ greater willingness to treat as physicians is mostly attributed to perceptions of higher obligations as a qualified doctor. There is greater but not total willingness to perform resuscitation on patients with HIV relative to other diseases. The increased willingness of preclinical students and the decreased willingness of clinical students both emphasise the importance of patient–physician communication and ethics studies during medical school. (shrink)

BackgroundCentral to ethically justified clinical trial design is the need for an informed consent process responsive to how potential subjects actually comprehend study participation, especially study goals, risks, and potential benefits. This will be particularly challenging when studying deep brain stimulation and whether it impedes symptom progression in Parkinson’s disease, since potential subjects will be Parkinson’s patients for whom deep brain stimulation will likely have therapeutic value in the future as their disease progresses.MethodAs part of an expanded informed (...) consent process for a pilot Phase I study of deep brain stimulation in early stage Parkinson’s disease, an ethics questionnaire composed of 13 open-ended questions was distributed to potential subjects. The questionnaire was designed to guide potential subjects in thinking about their potential participation.ResultsWhile the purpose of the study (safety and tolerability) was extensively presented during the informed consent process, in returned responses 70 percent focused on effectiveness and 91 percent included personal benefit as potential benefit from enrolling. However, 91 percent also indicated helping other Parkinson’s patients as motivation when considering whether or not to enroll.ConclusionsThis combination of responses highlights two issues to which investigators need to pay close attention in future trial designs: (1) how, and in what ways, informed consent processes reinforce potential subjects’ preconceived understandings of benefit, and (2) that potential subjects see themselves as part of a community of Parkinson’s sufferers with responsibilities extending beyond self-interest. More importantly, it invites speculation that a different paradigm for informed consent may be needed. (shrink)

The global public health threat posed by infectious disease is well recognised. The obligation to treat whilst exposed to risk, and its limits, is debated with each novel serious and communicable pathogen. Within national jurisdictions, different responses are forthcoming. Some, like France in 2009, give government the power to require healthcare staff to work, and even to requisition staff, including retired professionals. Others rely on notions of solidarity and professional duty, with scope for individual discretion. Our research with staff (...) in the West Midlands in 2008/2009– including non-professionals – suggested a strong correlation between feeling a duty to work and willingness to work during a pandemic. This was more influential than removing other barriers to working. Medical military personnel can already be ordered into risky situations. Our research in 2015/16 with those who worked in the Ebola treatment unit in Sierra Leone suggested that their concerns about risk were complex: the perceived magnitude of the risk was only one factor, even though tolerance was high. The type of risk and circumstances requiring that risk to be taken were also influential.Against this background, it will be argued, with caveats, that:military medical personnel should be willing to accept greater risk than civilian medical staff;and that to maintain national health services during a communicable disease emergency:civilian medical staff ought to accept greater risks than they currently appear willing to tolerate;conscription – from civilian or military populations – is permissible, even though it may elevate personal risk. (shrink)

In this introduction we set out some salient themes that will help structure understanding of a complex set of intersecting issues discussed in this special issue on the work of Marc Lewis: conceptual foundations of the disease model, tolerating the disease model given socio-political environments, and A third wave: refining conceptualization of addiction in the light of Lewis’s model.

RESUMEN La hiperhidrosis primaria, enfermedad crónica por exceso de sudoración, aparece en etapas tempranas de la vida y ocasiona limitaciones que interfieren las relaciones sociales. Esta sintomatología hace que la capacidad de control y tolerancia al estrés sea limitada. Se realizó una investigación descriptiva y se aportan resultados cualitativos individuales de tres jóvenes con hiperhidrosis primaria. Por ello el objetivo del presente trabajo es caracterizar el control y tolerancia al estrés asociados a la hiperhidrosis primaria que presentan tres jóvenes hiperhidróticos. (...) Fueron aplicados una entrevista semiestructurada, el Inventario de Ansiedad Rasgo-Estado y el Sistema Comprehensivo Rorschach. Los resultados son diferentes en los tres jóvenes. Se concluye que las diferencias entre las personas con hiperhidrosis primaria, en relación a su capacidad de control y tolerancia al estrés, están dadas por la combinación característica de elementos que definen la personalidad en estilos y estados en situaciones de demanda social mantenida. ABSTRACT Primary hyperhidrosis, a chronic disease characterized by excessive sweating, appears at an early age and causes limitations that interfere with social relationships. This symptomatology limits the ability to control and tolerate stress. A descriptive research was carried out. It shows the individual qualitative results of three young primary hiperhidrotic people. Therefore, the objective of this paper is to characterize stress control and tolerance associated to primary hyperhidrosis in three young hyperhidrotic people. A semistructured interview as well as the State-Feature Anxiety Inventory and the Rorschach Comprehensive System were used. Results are different in the three young people. It was concluded that differences between people with primary hyperhidrosis, with regard to their ability to control and tolerate stress, lie in the characteristic combination of elements that define the personality in styles and states in sustained social demand situations. (shrink)

Background: Parkinson’s disease is a neurodegenerative disease in which the progressive loss of dopaminergic neurons leads to initially sporadic and eventually widespread damage of the nervous system resulting in significant musculoskeletal and cognitive deterioration. Loss of motor function alongside increasing cognitive impairment is part of the natural disease progression. Gait is often considered an automatic activity; however, walking is the result of a delicate balance of multiple systems which maintain the body’s center of mass over an ever-changing (...) base of support. It is a complex motor behavior that requires components of attention and memory to prevent falls and injury. In addition, evidence points to the critical role of salient visual information to gait adaptability. There is a growing understanding that treatment for PD needs to address movement as it occurs naturally and walking needs to be practiced in more complex environments than traditional therapy has provided.MethodsIn this single-blinded randomized-controlled pilot study, an immersive treadmill training was piloted to determine feasibility and preliminary efficacy on gait and cognition in people with PD. Eighteen participants with Hoehn and Yahr stages I-III PD were randomized to either an intervention or a waitlist control group. Following baseline data collection, the intervention group trained for 30 min, three times/week for 4 weeks on a split belt treadmill combined with a first-person immersive video game targeting visuospatial skills and working memory. Assessment was repeated after 4 weeks of training for the experimental group and 1-month after baseline for the control group. Primary motor outcomes were captured with the APDM Opal sensors during 6 MWT, TUG, and TUG Cognitive. Secondary outcomes of cognition were measured with the Montreal Cognitive Assessment, Verbal Fluency and the Symbol Digit Modality Test. Within subject differences were calculated using the Wilcoxon Signed Ranked Test and between subject comparisons were analyzed using the Mann Whitney U-test.ResultsThis novel treadmill training program was well-tolerated with all participants in the intervention group completing 4 weeks of training three times a week without any adverse effects. After immersive cognitive motor training, the experimental group made clinically relevant improvements in gait speed and walking distance during the 6 MWT while members of the control group showed no change or decreased gait speed and walking distance over the 1-month trial. In addition, the experimental group demonstrated significant improvement for the TUG Cognitive and those changes were greater than the control group. The experimental group also improved scores on MoCA and SDMT cognitive outcome measures while the control group did not.ConclusionThe use of immersive gaming technology to engage specific areas of cognition related to gait is feasible in PD. The treadmill training program paired with a customized interactive video game improved walking velocity in addition to non-significant but consistent improvements in other gait measures and cognitive performance in participants with early to mid-stage PD. (shrink)

The novel coronavirus is an infectious disease that spread across the world, bringing with it serious mental health problems for men and women. Women in Pakistan are infected with COVID-19 at a much lower rate than men, yet report worse mental health. To explain this paradox, we surveyed 190 participants shortly following the country lockdown, focusing on perceptions of the COVID-19 impact and positive adjustment. Measures used in this study included the Warwick-Edinburgh Mental Well-being Scale and Distress Tolerance (...) Scale. Factor analysis revealed five distinct areas related to COVID-19, which did not differ by sex. However, men reported higher levels of both distress tolerance and well-being than women. High endorsement of actions to protect against COVID-19 was related to lower distress tolerance scores, but in different ways for men and women. Men, but not women, who endorsed more protective measures to stop the pandemic reported higher DTS absorption scores, and therefore being more consumed by distress; women who endorsed more protective measures to stop the pandemic reported less acceptance of distress than men, as reflected in DTS appraisal scores. An in-depth analysis of women’s beliefs and behaviors related to COVID-19 is warranted to understand why Pakistani women who are infected with COVID-19 at lower rates than men show more mental health symptoms. (shrink)

Taking regular walks when living with Parkinson’s disease has beneficial effects on movement and quality of life. Yet, patients usually show reduced physical activity compared to healthy older adults. Using auditory stimulation such as music can facilitate walking but patients vary significantly in their response. An individualized approach adapting musical tempo to patients’ gait cadence, and capitalizing on these individual differences, is likely to provide a rewarding experience, increasing motivation for walk-in PD. We aim to evaluate the observance, safety, (...) tolerance, usability, and enjoyment of a new smartphone application. It was coupled with wearable sensors and delivered individualized musical stimulation for gait auto-rehabilitation at home. Forty-five patients with PD underwent a 1-month, outdoor, uncontrolled gait rehabilitation program, using the BeatWalk application. The music tempo was being aligned in real-time to patients’ gait cadence in a way that could foster an increase up to +10% of their spontaneous cadence. Open-label evaluation was based on BeatWalk use measures, questionnaires, and a six-minute walk test. Patients used the application 78.8% of the prescribed duration and enjoyed it throughout the program. The application was considered “easy to use” by 75% of the patients. Pain, fatigue, and falls did not increase. Fear of falling decreased and quality of life improved. After the program, patients improved their gait parameters in the six-minute walk test without musical stimulation. BeatWalk is an easy to use, safe, and enjoyable musical application for individualized gait rehabilitation in PD. It increases “walk for exercise” duration thanks to high observance.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02647242. (shrink)

Deep brain stimulation is a well-established therapy for the motor symptoms of Parkinson’s disease, but there remains an opportunity to improve symptom relief. The temporal pattern of stimulation is a new parameter to consider in DBS therapy, and we compared the effectiveness of Temporally Optimized Patterned Stimulation to standard DBS at reducing the motor symptoms of PD. Twenty-six subjects with DBS for PD received three different patterns of stimulation while on medication and using stimulation parameters optimized for standard DBS. (...) Side effects and motor symptoms were assessed after 30 min of stimulation with each pattern. Subjects experienced similar types of side effects with TOPS and standard DBS, and TOPS were well-tolerated by a majority of the subjects. On average, the most effective TOPS was as effective as standard DBS at reducing the motor symptoms of PD. In some subjects a TOPS pattern was the most effective pattern. Finally, the TOPS pattern with low average frequency was found to be as effective or more effective in about half the subjects while substantially reducing estimated stimulation energy use. TOPS DBS may provide a new programing option to improve DBS therapy for PD by improving symptom reduction and/or increasing energy efficiency. Optimizing stimulation parameters specifically for TOPS DBS may demonstrate further clinical benefit of TOPS DBS in treating the motor symptoms of Parkinson’s disease. (shrink)

Prohibition on sex selection may well be unnecessary and oppressive as well as posing risks to women’s lives The urge to select children’s sex is not new. The Babylonian Talmud, a Jewish text completed towards the end of the fifth century of the Christian era, advises couples on means to favour the birth of either a male or a female child.1 The development of amniocentesis alerted the public in the mid-1970s to the scientific potential for prenatal determination of fetal sex,2 (...) and progressive decriminalisation of abortion afforded choice about continuation of pregnancy. The more recent emergence of preimplantation genetic diagnosis (PGD) obviates resort to abortion, and improved techniques of sperm sorting and diagnosis permit creation of zygotes that will ensure the sex of a future child. Growth of biomedical means to select the sex of future children has been accompanied by fear that such means will be employed to favour births of sons, and so perpetuate devaluation of girl children and women’s inferior family and social status. A reaction to this fear has been the demand for legal and medical professional prohibition of sex selection techniques. For instance, the Council of Europe’s Convention on Human Rights and Biomedicine3 provides in article 14 that: The use of techniques of medically assisted procreation shall not be allowed for the purpose of choosing a future child’s sex, except where serious hereditary sex-related disease is to be avoided. Legislation has been enacted in a number of countries, and proposed in others, to prohibit sex selection on non-medical grounds, such as the Prenatal Diagnostic Techniques (Regulation and Prevention of Misuse) Act, 1994 in India. In Canada, for instance, government draft legislation introduced in May 2002 proposes to make it a crime for any person, for the purpose of creating a human …. (shrink)

Chemokines (chemotactic cytokines) drive and direct leukocyte traffic. New evidence suggests that the unusual CCR6/CCL20 chemokine receptor/ligand axis provides key homing signals for recently identified cells of the adaptive immune system, recruiting both pro‐inflammatory and suppressive T cell subsets. Thus CCR6 and CCL20 have been recently implicated in various human pathologies, particularly in autoimmune disease. These studies have revealed that targeting CCR6/CCL20 can enhance or inhibit autoimmune disease depending on the cellular basis of pathogenesis and the cell subtype (...) most affected through different CCR6/CCL20 manipulations. Here, we discuss the significance of this chemokine receptor/ligand axis in immune and inflammatory functions, consider the potential for targeting CCR6/CCL20 in human autoimmunity and propose that the shared evolutionary origins of pro‐inflammatory and regulatory T cells may contribute to the reason why both immune activation and regulation might be controlled through the same chemokine pathway. (shrink)

Resident microbiota do not just shape host immunity, they can also contribute to host protection against pathogens and infectious diseases. Previous reviews of the protective roles of the microbiota have focused exclusively on colonization resistance localized within a microenvironment. This review shows that the protection against pathogens also involves the mitigation of pathogenic impact without eliminating the pathogens (i.e., “disease tolerance”) and the containment of microorganisms to prevent pathogenic spread. Protective microorganisms can have an impact beyond their niche, (...) interfering with the entry, establishment, growth, and spread of pathogenic microorganisms. More fundamentally, we propose a series of conceptual clarifications in support of the idea of a “co-immunity,” where an organism is protected by both its own immune system and components of its microbiota. -/- . (shrink)

Positive frequency dependent selection is a natural selection regime where the fitness of a phenotype increases with its frequency in the population. Examples can be typically found in the spread of disease tolerance strategies in a population. A characterizing feature of PFDS is that the focal allele may experience favorable selection only when it becomes more frequent in the population, while being selected against when it is rare. In this paper, by applying a solution concept from evolutionary game (...) theory, we hypothesize that the process of emergence of such alleles triggers selection for silence, where the emergence of alleles that can stay unexpressed for a period of time will be favored by selection forces. We illustrate our hypothesis using a mathematical model of a population of single locus diploid organisms with two alleles where a single mutant of an allele that experiences positive frequency dependent selection appears in a population where the other allele is a dominant. The model results show that the longer the silence interval of the new mutant before its expression, the better its chances of getting fixed in the population. However, this effect will be observable only to a certain limit after which further increase in the interval will not have an effect on the expected fixation rate. Two divergences from the simple scenario are also investigated: the nonsynchronous expression of the focal allele and its emergence in a spatial grid limited by a migration bottleneck. In all cases, it is shown that there is an evolutionary pressure inherent in the dynamics of positive frequency dependent selection on the genes to have a delayed expression. It is hypothesized that the regulation systems of such traits will be under selection for either internal silencing mechanisms or to be triggered by an external environmental condition. (shrink)

Resident microorganisms, known as the microbiota, are essential for many physiological functions including protection against pathogens. Microbiota is indeed required for proper immune system development and function, and can also host-independently protect against infections. Thus, a co-constructed view of host protection involving both host and microbiota, named ’co-immunity,’ has been proposed, and the idea of an ’immunological holobiont’ has been suggested. Yet this view of co-immunity might be too limited, as experimental work has shown that the immune system is involved (...) in functions other than protection, essentially development and repair. Microbiota, through co-immunity, is thereby most likely involved in these functions, although strong evidence is currently lacking. Moreover, as our point of view is mainly host-centered, we may miss the implications of co-immunity at broader scales, including cellular and population levels. Intriguingly, co-immunity effects could be beneficial for one function and/or one level, while being detrimental for others. All these elements should be taken into consideration for microbiota manipulation, in order to avoid potentially harmful side effects. (shrink)

Neuroscience has substantially advanced the understanding of how changes in brain biochemistry contribute to mechanisms of tolerance and physical dependence via exposure to addictive drugs. Many scientists and mental health advocates scaffold this emerging knowledge by adding the imprimatur of disease, arguing that conceptualizing addiction as a brain disease will reduce stigma amongst the folk. Promoting a brain disease concept is grounded in beneficent and utilitarian thinking: the language makes room for individuals living with addiction to (...) receive the same level of compassion and access to healthcare services as individuals living with other medical diseases, and promotes enlightened social and legal policies. However such claims may yield unintended consequences by fostering discrimination commonly associated with pathology. Specifically, the language of neuroscience used to describe addiction may reduce attitudes such as blame and responsibility while inadvertently identifying addicted persons as neurobiological others. In this paper, we examine the merits and limitations of adopting the language of neuroscience to describe addiction. We argue that the reframing of addiction in the language of neuroscience provides benefits such as the creation of empowered biosocial communities, but also creates a new set of risks, as descriptive neuroscience concepts are inseparable from historical attitudes and intuitions towards addiction and addicted persons. In particular, placing emphasis on the diseased brain may foster unintended harm by paradoxically increasing social distance towards the vulnerable group the term is intended to benefit. (shrink)

Cancer is generally defined as uncontrollable growth of cells caused by genetic aberrations and/or environmental factors. Yet contagious cancers also occur. The recent emergence of a contagious cancer in Tasmanian devils has reignited interest in transmissible cancers. Two naturally occurring transmissible cancers are known: devil facial tumour disease and canine transmissible venereal tumour. Both cancers evolved once and have then been transmitted from one individual to another as clonal cell lines. The dog cancer is ancient; having evolved more than (...) 6,000 years ago, while the devil disease was first seen in 1996. In this review I will compare and contrast the two diseases focusing on the life histories of the clonal cell lines, their evolutionary trajectories and the mechanisms by which they have achieved immune tolerance. A greater understanding of these contagious cancers will provide unique insights into the role of the immune system in shaping tumour evolution and may uncover novel approaches for treating human cancer. (shrink)

Staphylococcus aureus is an opportunistic pathogen capable of causing a variety of diseases including osteomyelitis, endocarditis, infections of indwelling devices and wound infections. These infections are often chronic and highly recalcitrant to antibiotic treatment. Persister cells appear to be central to this recalcitrance. A multitude of factors contribute to S. aureus virulence and high levels of treatment failure. These include its ability to colonize the skin and nares of the host, its ability to evade the host immune system and its (...) development of resistance to a variety of antibiotics. Less understood is the phenomenon of persister cells and their role in S. aureus infections and treatment outcome. Persister cells occur as a sub‐population of phenotypic variants that are tolerant to antibiotic treatment. This review examines the importance of persisters in chronic and relapsing S. aureus infections and proposes methods for their eradication. (shrink)

Some patients tolerate a given drug well, without adverse reactions. For others, though, an identical dose of the same medication can have toxic effects. Moreover, while a drug can be effective at relieving symptoms for some patients, it may fail to do the same for others suffering with the same disease. With such variability in treatment responses, tailoring medical interventions to individual patients has long been an aspiration of medicine. Until recently, however, medicine lacked a clear understanding of the (...) biological reasons for human variation in drug response. Attempting to adjust treatment to the individual patient, physicians have relied primarily on direct observation, trial-and-error, and, ultimately... (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)

Ex interiore ipso exeas. Preface. This book reconstructs the history of a still open dialectics between several ethoi, that is, shared codes of unwritten rules, moral traditions, or self-aware attempts at reforming such codes, and ethical theories discussing the nature and justification of such codes and doctrines. Its main claim is that this history neither amounts to a triumphal march of reason dispelling the mist of myth and bigotry nor to some other one-way process heading to some pre-established goal, but (...) instead to a chain of controversies where the partners’ will to win unintentionally yields a wealth of insights on human existence that has still something to teach us. -/- 1. The Hellenic moral tradition. -/- Two different traditions of morality in vi-v century Greece are described. The birth of philosophical questioning of traditional morality and temporal and spatial variation of custom is described within the context of the v century crisis, the demise of traditional aristocratic and tyrannical rule and the birth of democracy. Two conflicting answers to the challenge are reconstructed, namely conventionalist or immoralist theories formulated by the Sophists and the eudemonist and intellectualist Socratic theory. -/- 2. Plato and the Good. -/- Plato’s own reformulation of Socrates rejoinder to the Sophists is reconstructed. His psychological views, his classification of the four cardinal virtues and his political theory are described as parts of a unitary system, culminating in an extremely realist moral ontology identifying the idea of the good with the essence of the (moral and extra-moral) world itself. -/- 3. Aristotle and practical philosophy. -/- Aristotle’s invention of practical philosophy as a field separated from first philosophy is shown to be an implication of his break with Plato moral ultra-realism. Aristotle’s agenda in his moral works is arguably dependent on a polemical intention, namely dismantling Socratic intellectualism. The semi-inductive or virtuously circular method of practical philosophy is illustrated, starting with the received opinions of the better and wiser individuals and trying dialectically to sift what is left of mistake and inconsistency in such opinions, finally trying to correct mistakes and make the overall practical science more consistent. The relationship of individual ethics, or ‘monastics’, with the art and the science of the pater families, or ‘economics’, and the science of the ruler and citizen, or politics, is illustrated. The nature of virtues, or better, excellences of character, is discussed, highlighting the basic role of hexes, or ‘dispositions’. Prudence, or better, practical wisdom, is the focus of the chapter. Its relationship with boùleusis or deliberation is discussed, and its autonomous status vis-à-vis theoretical knowledge is stressed. -/- 4. Cynics and Stoics: ethics as therapy. -/- The chapter provides an overview of Hellenistic ethics, which almost amounts to Hellenistic schools of philosophy, in so far as ‘philosophy’ became in these centuries primarily the name for a way of life. The typical character of the Cynical movement is highlighted, that of a school of life, not a school aimed at providing any kind of intellectual training was to be provided. The various phases of Stoicism are described, and the shifting place that was given to ethics in the Stoic system of idea, culminating in the paradoxical view of ethics, its impossibility in principle notwithstanding, as the only truly significant and necessary part of philosophy. The peculiar character of the Epicurean school is described, a combination of the science of well-being aiming, more than pleasure understood as in the popular view, the reduction of useless suffering, of unnecessary needs, and at a balanced selection of pleasures of the best and most durable kind. -/- 5. Roman and Imperial Moralists. -/- The chapter is dedicated to the reconstruction of a particular kind of literature, whose specific features have long been under-stressed, namely the Roman and Imperial moral literature. Cicero is treated at some length, showing how his own synthesis of various Hellenistic trends is as a truly philosophical enterprise, deserving serious consideration after one or two centuries when he was confined to the role of literate. Epictetus is given pride of place, stressing the novelty of his approach to ethics as cognitive therapy, in this case just following an already existing new wave of interest after nineteenth-century oblivion justified by alleged lack of authentic ‘philosophical’ character. -/- 6. The Hebrew moral tradition. -/- A reconstruction of basic ideas from a few books of the Hebrew Bible is provided, starting with the Prophetic tradition and the focus on God’s mercy as the source of motivation and standard for human behaviour. Then a comparative analysis is undertaken of a parallel tradition, namely the three codifications of the Torah (Law or, better, Instruction), highlighting how a core of moral ideas may be recognized as a basis and preamble of codification of civil law, cultural practice, and regulation of ritual purity. The importance of Levitic is stressed as the turning point when the stress on mercy, typical of the Prophetic tradition, starts being combined with legal tradition yielding the change in the sensibility of the Second Temple time. -/- 7. Second Temple Judaism. -/- This chapter describes the Long March leading from the post-exile Zadokite restoration to the first-century aevi vulgaris. The first topic reconstructed is the Zadokite theology of the double retribution. The second is the alternative Enochic tradition consistently rejecting the central role of the Temple, the Priesthood and worship as atonement for sins and offering as an alternative God’s unlimited mercy and preaching mercy, not sacrifice as the way of behaving requested by God. Wisdom literature, the third subject discusses, is a kind of third way, on the one hand increasingly critical towards the double retribution and ruling theology’s optimism facing the world as it is and on the other mocking at the Enochic current as a band of dreamers and visionaries. The third way consists in disenchantment facing the word as it is combined with a refusal of vain and childish hope of prizes for the righteous, suggesting instead the leading idea of right deeds for righteousness’s sake. Rabbi Hillel, Rabbi Yeshua and Philo of Alexandria are described as the three leading figures at the culminating point of such process of emergence of a new sensibility, gradually including mercy as an essential part of justice and establishing the starting point of both the Rabbinic and the Christian tradition. This starting point consists precisely in the precept of one’s neighbour’s love or of the golden rule, whose meaning is, arguably, more consistent than a long-lasting Christian tradition deriving from John and Augustine made us believe. And Christian morality, vis-à-vis allegedly legalist ‘Ancient Testament’ teachings, is less of a novelty than most early Christian writers announced. -/- 8. Talmudic moral doctrines and proto-Christian paraenesis. -/- The first three sections examine the moral doctrines of so-called 'ethical Treaties' from the Talmud, a group of treaties, among which the best known is Pirke Avot, that were left out of the six "orders" of the canon as they did not fit in any of the six groups of issues ritual or legal on which the division was based. According to Maimonides, their peculiar theme is provided by the Deot, 'opinions', i.e., mental dispositions, that is, the translation of the Greek term hexes and Arab akhlak (in turn providing in this language the name for ethics as such). The three topics I reconstruct are: i) the notion of Torah: The Torah is understood as the world order itself, or as the ‘Wisdom’ that existed even before creation and was "the tool by which the world was built"; however, the Torah is an earthly and human entity, as it was "received" by humans, and from that very moment belongs to them; ii) the relationship between love of God and love of neighbour; the treaties require us to study and practice the Torah ‘for its own sake’, that is, require us to act out of love, not out of fear or hope of reward; iii) the idea of sanctification of daily life: having disappeared with the destruction of the Temple the possibility of any conflict between liturgical service and everyday life, the latter is assumed to be in itself divine service: to give food to the poor has the same value as sacrifices in the Temple, and as an implication, the insistence become recurrent on the goodness of created things in themselves along with a polemic against ascetic currents. The conclusions drawn are: i) the moral teachings of the Talmud and those of Yeshua are, rather than similar, virtually identical; one may safely say that the precept of love and the golden rule are central ones for all Talmudic rabbis, that mercy plays an indispensable role alongside with justice, and the latter is not a different thing from one’s neighbour’s love; ii) a peculiarity of Talmud rabbis facing Yeshua is the idea of study as worship, and knowledge as a source of justice; but this is an idea of Judaism after the Temple's destruction that cannot be attributed to the Pharisees of Yeshua’s time; iii) the relation of study and practice in the Talmud parallels that between faith and deeds in Paul's epistles, that is, respectively faith or learning are a necessary and sufficient condition to be recognized as righteous, but deeds are the inevitable effect of either faith or learning. The last two sections examine first the various Christian currents and then Gnostic para-Christian or non-Christian currents as well as Manicheism. The sayings ascribed to Yeshua are examined first, yielding the conclusion that a close equivalent may be found for every saying in Talmudic literature and yet the whole is ascribed to one rabbi, with rather consistent stress on God’s mercy and unconditional forgiving as the mark of true imitation of God. Thus, Yeshua’s teaching is pure, purest Judaism. The last section describes briefly the galaxy of Gnostic currents and Manicheism, trying to sketch the profile of moral teachings resulting from an encounter of Asian spiritual traditions, Hellenistic lore and sparks of teachings from apocalyptic Jewish currents. -/- 9. Christianity as “philosophy”. -/- The chapter reconstructs the stormy story of several encounters between Christian currents and Hellenistic philosophical schools. The first one was with late Cynicism. Recent, rather controversial, literature discovered the jargon and several rhetorical topics from the Stoic and Cynical popular philosophy in a few books from the New Testament itself. This, far from proving that Rabbi Yeshua himself had been influenced by cynical preachers, is a proof of the necessity to translate the original Christian message in a Greek lexicon deeply impregnated with cynic terminology. The second was with Platonism, yielding the mild and temperate moral teaching of Clemens of Alexandria, teaching the sanctity of nature and the human body, the joy of moderate fruition of ‘natural’ kinds of pleasures, and the beauty of the marital life – in short, the opposite of the standard picture of Medieval Christianity. Ambrose of Milan brings about a different kind of synthesis, namely with Middle Platonism, where Stoic themes prevail. The most shocking case is Augustine, where early Manichean education is overcome in a former phase by a synthesis of Plotinian Neo-Platonism and Christian preaching, yielding a sustained polemic with the Manicheans and rather optimistic views on life and Creation, the body and sexuality, and Hebrew-Judaic tradition not far from Clemens of Alexandria. In a later phase, occasioned by controversy on the opposite front, with such Christian currents as the Pelagians and Donatists, Augustine comes back to heavily anti-Judaic and world-denying ascetic attitudes where is earlier Manichean upbringing seems to emerge again. The tragedy of medieval Christianity will be the later Augustine’s overwhelming influence. A final section is dedicated to the monastic tradition where a curious mixture of world-denying asceticism with an astonishingly penetrating ‘science’ of introspection emerges. -/- 10. Ethics in the Arabic-Islamic Philosophy. -/- The Qurān and the qadit, that is, collections of sayings ascribed to the prophet Muhammad contain a wealth of precepts and catalogues of virtues mirroring moral contents from the Jewish and the Christian traditions, among them the basic notion of imitation of the Deity, where mercy is assumed to be its basic trait. An important tradition within Islam, namely Sufism, stressed to the utmost degree the role of mercy, turning Islam into a mystic doctrine centred on the retreat from the world, abandonment to God’s will, and a peaceful and fraternal attitude to our fellow-beings. A secular literary tradition originating in the Sassanid Empire, the literature of advice to the Prince, had for a time a widespread influence in the newly constituted Arabic-Islamic commonwealth. In a later phase, the legacy of Hellenic philosophy made its way into the intellectual elite of the Islamic world. The first important legacy was Platonic, and the Republic became the main text for Islamic Platonism. In a second phase also Aristotelian and Stoic influence were assimilated. Miskawayh’s treatise was the masterwork at the time Arabic philosophy reached its Zenith. It is a treatment of the soul’s diseases and their remedies, combining the Aristotelian doctrine of the golden mean with the Stoic doctrine of the passions and elements of Galenic medicine. Towards the eleventh-twelve centuries, a war raged among theologians and philosophers, finally won by the former with the disappearance of philosophy as such. The newly established mainstream, yet, was no kind of intolerant fanaticism. It drew from the work of mystic theologian Al-Ghazālī, the best heir of Sufism, teaching a tolerant and peaceful attitude to our fellow-beings and a passive attitude to destiny as an expression of the Divine will. -/- 11. Ethics in the Jewish philosophy. -/- The encounter between the Talmudic tradition and Hellenic philosophy had taken place for the first time in Alexandria at the time of Philo but the two traditions had parted way again. In fact, the kind of Platonic Judaism founded by Philo survived only within Christianity, in the fourth Gospel and then in writings by Clemens of Alexandria. The Talmudic literature had absorbed too a few traits from the Hellenic Philosophy, namely an idea of ethics as care of the self and a role for the education of character as propaedeutic to theoretical knowledge. In the Arabic-Islamic world, a second round started when Jewish authors writing in Arabic undertook the task to prove the full compatibility of the tradition deriving from Tora and Platonic philosophy. The culmination of this attempt is provided by Moshe ben Maimon who tried to use Aristotelian ethics as a language into which the teaching from the Pirke Avot could be translated. -/- 12. The practical philosophy revival in Latin Europe. -/- A reconstruction is carried out of a fresh start of philosophical ethics in Latin Europe at the turn of the Millennium rescuing a Platonic and Augustinian legacy, with Anselm and Peter Abelard. In this phase remarkable innovations are introduced, including Abelard’s claim of the obliging character of erring consciousness. In a second phase, the rediscovery of Nicomachean Ethics thanks to Latin translation of Arabic versions, gives birth to a new wave of ethical studies, recovering the very idea of Aristotelian practical philosophy, with the potential implication of a full legitimization of natural morality, i.e. ethics without Revelation. -/- 13. Scholastic practical philosophy: Thomas Aquinas. -/- Aquinas’s ethics is theological ethics out of which it would be vain to try to extract self-contained philosophical ethics. His treatment of topics in philosophical ethics, yet, does not boil down to the repetition of Aristotelian arguments but is rather a creative reshaping of such arguments. For example, he introduces also in the practical philosophy a first principle parallel to the principle of non-contradiction; and he also carries out a synthesis of Aristotelianism, Stoicism, neo-Platonism. Even though it is essentially moral theology, Aquinas’s doctrine - unlike Augustine – grants full citizenship to "natural" morality, firstly by rejecting the claim that the corruption of human nature due to the original sin is so radical as to leave pure nature incapable of moral goodness. The doctrine is presented in a more sophisticated formulation in a few of the Quaestiones such as De Malo and De Veritate, in the Summa contra Gentes and in the commentaries to Aristotle than in the famous Summa Theologica, but the latter work includes the only or the largest exposition of some decisive part of the theory. Thus, the Summa Theologica should be read for what it is more than criticized for not being what it was not meant to be. It was not meant to be the brilliant synthesis of all that Reason he had been able to produce with what Revelation had added about which the Neo-Thomists used to dream, but rather a manual for the training of preachers and confessors, where theoretical claims are not too ambitious, and a few serious tensions are left. Besides a jump between the Prima Secundae and the Secunda Secundae, being the former an essay in virtue theory and the latter a handbook for confessors, the most serious tension is perhaps the one between the ethics of right reason presented in most of Prima Secundae and the eudemonistic ethics developed in quaestiones 1-5 of the same part; the alternative ethical theory which also may be found in Augustine, the Stoic view of a cosmic reason eventually coincident with the moral law, was believed by Anselm (followed by John Duns Scotus and William of Ockham) to be incompatible with eudemonism. It is questionable whether Thomas was able to solve the tension proving that it is just an apparent tension, in so far as the right reason and bliss derived from the knowledge of God tend to coincide, but this is just a conjecture. Thomas’s ethics is a virtue ethics, not a law-based one, and moral judgment focuses on the virtues, particularly charity, not on the commandments and even less on absolute prohibitions; Thomas, however, would not have considered a drastic alternative between law and the virtues such as the one which has been advanced in late twentieth-century philosophy to be justified. Nonetheless, when it discusses ‘special’ virtues, it ceases to be an ethics of virtue and becomes a disappointing and often contradictory discussion of legal and illegal acts. Such a discussion takes most of the time ‘reasonable’ middle positions on controversial issues but not the alternative approach that Aristotelianism would have made possible; even when some occasional Aristotelian claim shows up, such as money’s barrenness as a reason against usury, this seems to be made by an author who apparently ignores the Aristotelian Thomas of the Prima Secundae. It is an ethic of human autonomy which recognizes the binding character of the individual conscience and, potentially, even a duty to disobey unjust laws. It is true that what Thomas writes in his discussion of the death penalty and persecution of heretics is simply disgusting, and yet we should blame Thomas the man, not the Thomist ethical theory. Finally, Thomas’s ethics is no way an ethical ‘absolutism’, as both the traditionalist Catholic theologians and secularists tend to believe, but rather an ethic of prudential judgment on the individual case. Exceptions to this approach – or better the result of logical fallacies – are provided by the thesis of the absolute character of negative precepts and of the existence of so-called intrinsically evil acts, a thesis that would simply cease to make sense in the light of Thomas’s own distinction between human act and natural act, carrying consequences that Thomas did not live long enough to draw. -/- 14. Scholastic practical philosophy: John Duns Scotus and William of Ockham. A reconstruction is carried out of the ethical doctrines by both most authoritative Franciscan doctors. Their continuity with Aquinas is vindicated against prejudice carried by centuries of polemics within the Catholic Church and tendentious disparaging of both as forerunners of execrable Reformation. Besides aspects of continuity, also the important novelties are illustrated, first John’s abandonment of Aquinas’s and Augustine’s eudemonism, asserting righteousness for righteousness’s sake, and then William’s explicit defence of the philosopher’s virtues, that is, natural morality, and his solution to the dilemma of God’s omnipotence and the universal validity of natural law extending to God himself. -/- 15. Aristotelianism interpreted by the Magistri Artium. -/- A reconstruction of the until recently forgotten ethical doctrines by the Parisian Magistri Artium, falsely depicted as ‘Averroists’ and either deprecated as heretics or mistaken for predecessors of modern secularism. In fact, they illustrate a view of ‘natural’ virtue as may be understood by human reason without the assistance by Revelation. -/- Etiamsi daremus Deum non esse. Intermediate considerations. Three considerations may be suggested by the story told in the book. The first one is that intellectual histories have been mounted in the past with the same state of mind as one may mount a war chariot. Such constructions are not very helpful as tools for understanding the past. Wars waged in the past have left the field obstructed by ruins not easy to remove even by those historians who have animated by an impartial academic motivation. They have been influenced too by consequences of past emphasis on some authors and damnatio capitis suffered by others, by stratifications left on sources by secondary literature and translations, by allotment of originally close sources to different literary genres, by the monopolization of religious texts by churches with full cooperation by secular scholars who still fear contamination. The second one is that aware or unaware ethnocentrism has carried various calamities to our comprehension of the past. Their last vestiges have surfaced again in the semi-scholarly discussion on the idea of Europe occasioned by the debate on a project of a European Constitution. Mention of Europe’s Christian roots has been the clumsiest move. Proclamations of such roots were so obvious in what they affirmed as they were totally off-path concerning what they omitted, namely that he modern European moral tradition included legacies from Middle-Eastern wisdom, Hellenic philosophy, Roman Imperial legal literature, and, besides, a Jewish legacy in turn incorporating other more ancient Middle-Eastern legacies and which has been partly conveyed by Christianity. And the Islamic-Arabic philosophy too, in so far it made the Nicomachean Ethics available to Latin Christian scholars, is one more of Europe’s roots. The third is that religious traditionalists and secularist fundamentalists have gone hand in hand for a couple of centuries in either extolling or deprecating the allegedly Modern idea of Ethics without God, first formulated by Hugo Grotius with the claim that natural law would still be valid ‘etiamsi daremus – quod sine summo scelere dari potest – Deum non esse’. The facts are, firstly, that this is not an irreligious claim and Grotius was just a pious and meek Christian and, secondly, that it is not a ‘modern’ claim but rather one more formulation of the claim that there is a natural morality, independent of divine revelation, a claim shared by Moshe ben Maimon, Aquinas and William of Ockham. -/- . (shrink)

A pathogenic connection between autoreactive T cells, fungal infection, and carcinogenesis has been demonstrated in studies of human autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy as well as in a mouse model in which kinase-dead Ikkα knock-in mice develop impaired central tolerance, autoreactive T cell–mediated autoimmunity, chronic fungal infection, and esophageal squamous cell carcinoma, which recapitulates APECED. IκB kinase α is one subunit of the IKK complex required for NF-κB activation. IKK/NF-κB is essential for central tolerance establishment by regulating the development of (...) medullary thymic epithelial cells that facilitate the deletion of autoreactive T cells in the thymus. In this review, we extensively discuss the pathogenic roles of inborn errors in the IKK/NF-κB loci in the phenotypically related diseases APECED, immune deficiency syndrome, and severe combined immunodeficiency; differentiate how IKK/NF-κB components, through mTEC, T cells/leukocytes, or epithelial cells, contribute to the pathogenesis of infectious diseases, autoimmunity, and cancer; and highlight the medical significance of IKK/NF-κB in these diseases. IKK/NF-κB regulates the expression of many genes that encode proteins involved in many crucial biological functions, such as immunity, tissue homeostasis, and fungal/bacterial/viral infections. Also, IKKα plays anti-tumor activities in many organs independently of NF-κB pathways. Thus, an inborn error in one of these gene loci can cause severe human diseases through these complicated mechanisms. (shrink)

Since the emergence of psychology, its relation with religion has been inconsistent. Their different sources and methodologies but common aims made them close or distanced. Today these disciplines acknowledged and learned to benefit from each other. The affect of religion/spirituality on human’s lives raised the attention of psychology and required the integration of these into psychotherapy. In order to approach the psychology-religion relation via the traces of religion within psychotherapy the paper deals with the necessity, the knowledge needed, the principles (...) when integrating religious/spiritual principles and practices into psychotherapy; finally the religious traces in psychotherapy. The paper comprises few Turkish examples together with the huge body of theoretical and practical examples on the topic. These theories and practices should be important examples for Turkey. By addressing the religious traces in psychotherapy the aim of the paper is to show that the cliff between psychology and religion is in fact not that deep.SummaryIt can be argued that psychology and religion have common interests relating the well-being of individuals. There is a huge body of research that emphasizes the implementation and necessity of cultural, religious, spiritual principles in professional psychology. The proprium of these models is to integrate the client’s religious/spiritual sources into therapy. Especially religious clients benefit from therapies that define their treatment goals around their religious views. However, it must be considered that if the disorder has a biological dimension and/or is severe psychopathologic pure religious interventions will not be sufficient. This paper traces the religious/spiritual principles within psychotherapies and shows that the cliff between religion and psychology is not that deep.At different places in the world therapy is done according to western standards. However, determining mental health or disorders according to western criteria might be problematic. In societies in which religious/spiritual life is an essential part of culture, religion plays a crucial role in people’s perception of disease and treatment. In mental health, spirituality is an important and primary source for coping. Empirical studies reveal the positive outcomes of religious practices such as personal prayer, repentance, meditation, and dhikir on mental and physical health. In light of this data it becomes clear that psychotherapies should be revised socio-culturally and culturally sensitive psychotherapies that cover belief and religious practices should be developed. Another need for the integration of religion, belief, and spirituality with psychotherapy is the significant effect of these experiences on individual’s lives. With regard to the broad impact of religion, psychological interventions solely might not be sufficient to fulfill human psychological needs. As studies show, religious clients expect religious practices in treatment as well as a therapist who is open and respectful to religious principles, ready to talk about own religious beliefs, willing to integrate religious matters into therapy. To fulfill these expectations therapists, need to be trained and educated in religious/spiritual matters. Additionally, the therapist must acknowledge and be conscious about her/his own worldview, religious commitment, and spiritual life. However, the therapist needs not to be religious him/herself or share the same religion as the client. It is sufficient that the therapist is open and receptive to the client’s beliefs so that these can be used as effective sources in therapy. Spiritual psychotherapy considers spirituality as one of the main sources of clients. Thus, it might be critical when the therapist has poor knowledge about religion when the client considers it as significant. This source might be helpful for the client in coping with his/her problems and limitations. Having knowledge about the client’s religion and culture might also be important to acknowledge his/her perceptions and beliefs. Because individuals’ understanding of disease, their beliefs about reasons for mental disorders, their expectations from the health system are important factors in seeking help and choosing therapy.Therapists who decide to integrate spiritual/religious principles into psychotherapy have to adhere to some ethical principles. The source and the degree of the psychological disorder are important, too. Even though the efficacy of religious rituals and spiritual interventions are extensive in each case it has to be investigated whether religiosity/spirituality is part of the problem or the solution. Certain aspects will guide the therapist in deciding whether to integrate religiosity/spirituality into the therapy process or not. Additionally, he/she has to gather information about the client’s religious/spiritual life (spiritual anamneses) in order to choose the most appropriate religious method and intervention. Today psychotherapy deals with coping, questions about the meaning, purpose, and way of life. Actually, these are issues with which religious traditions has dealt and proposed solutions for thousands of years ago. For example, ethical principles for mental health professionals correspond to those of religious teachings. The attitudes and the type of relationship recommended by the client-centered approach are also commended by religious teachings for all human relations. Beginning with the 1960’s an increasing interest in Buddhist teachings is observable among psychotherapists. Mental exercises (especially meditation) cause transformations in the self-perception and lead to enduring changes in consciousness. Religions such as Islam, Judaism, and Buddhism recommend meditation technics like contemplation, dhikr, and yoga. Confession in the Catholic Church has similarities with psychotherapeutic catharsis. Many cultures own one kind of forgiveness rituals of confessions. As studies report people benefit from these rituals. Forgiveness is a multifaceted issue with psychological and spiritual dimensions and involves cognitive, emotional, relational, and spiritual processes. Research indicates the religious and psychological functions of forgiveness. Many subjects such as personal prayer, hope, empathy, love, and tolerance are common issues of both, psychotherapy and religion/spirituality. Different psychotherapeutic approaches and especially positive psychology integrate these values that are valued by religion/spirituality into their theories and practices.In conclusion, the cliff between psychology and religion/spirituality is not that deep at it seems at first sight. They have many subjects in common. Individuals turn to religion and spirituality in times of crises. This makes it inevitable to include religion and spirituality into the therapeutic process. Because religions provide ways of coping, hope, and meaning in difficult times. This fact is recognized and accepted abroad and lead to the religious/spiritual psychotherapy movement, which will hopefully an inspiration for Turkish psychology as well. (shrink)

The field of Neuro-Engineering seems to be on the fast track towards accomplishing its ultimate goal of potentially replacing the nervous system in the face of disease. Meanwhile, the patients and professionals involved are continuously dealing with human bodily experience and especially how neuro-engineering devices could become part of a user’s body schema: the domain of ‘embodied phenomenology’. This focus on embodiment, however, is not sufficiently reflected in the current literature on ethical and philosophical issues in neuro-engineering. In this (...) article we will focus on this lacuna by explaining existing data on neuro-engineering user’s experiences by using phenomenological concepts such as transparency and the concepts that may facilitate this: functionality, sensorimotor feedback and affective tolerance. By introducing and applying these concepts to four real life case examples, we will discuss practical implications and guidelines which can contribute to the actual success of incorporation of the device by the patient. First, we will discuss the importance of a ‘Patient Preference Diagnosis’, which can serve as a way to prepare the patient for the existential reorientation involved in the process. In addition, a Patient Transparency Diagnosis during and after such a process is also relevant when wanting to provide the medical field in general with feedback, and the patient in particular with possibilities to fine-tune the device. From these practical guidelines we will conclude that the phenomenological approach can be very valuable when applied to the field of neuro-engineering. (shrink)

Background Past studies emphasized the possible cultural influence on attitudes regarding reprogenetics and reproductive risks among medical students who are taken to be “future physicians.” These studies were crafted in order to enhance the knowledge and expand the boundaries of cultural competence. Yet such studies were focused on MS from relatively marginalized cultures, namely either from non-Western developing countries or minority groups in developed countries. The current study sheds light on possible cultural influences of the dominant culture on medical students (...) in two developed countries, potentially with different dominant cultures regarding reprogenetics and reproductive risks: Israel and Croatia. Methods Quantitative-statistical analyses were employed, based on anonymous questionnaires completed by 150 first year medical students in Israel and Croatia. The questionnaires pertained to the knowledge and attitudes regarding genetics, reproduction and reproductive risks. These questionnaires were completed before the students were engaged in learning about these topics as part of the curriculum in their medical school. Results Substantial differences were revealed between the two groups of medical students. Israeli medical students were less tolerant regarding reproductive risks and more knowledgeable about genetics and reproductive risks than Croatian medical students. For example, while nearly all Israeli medical students disagreed with the idea that “Screening for reproductive risks in prospective parents is wrong,” less than 40% of their Croatian counterparts shared a similar stance. Similarly, all Israeli medical students correctly observed that “A carrier of a recessive genetic disease actually has the disease” was wrong, as opposed to only 82% of Croatian students. Conclusions By linking applicable theoretical literature to these findings, we suggest that they may reflect the hidden influence of the dominant culture in each country, disguised as part of the “culture of medicine.” Acknowledging and learning about such influence of the dominant culture, may be an important addition to the training of medical students in cultural competence, and specifically their cultural awareness. Such an acknowledgement may also pave the road to drawing the attention of existing physicians regarding a less known yet an important aspect of their cultural competence, insofar as the cultural awareness component is concerned. (shrink)

The thymus is a unique primary lymphoid organ that supports the production of self‐tolerant T‐cells essential for adaptive immunity. Intrathymic microenvironments are microanatomically compartmentalised, forming defined cortical, and medullary regions each differentially supporting critical aspects of thymus‐dependent T‐cell maturation. Importantly, the specific functional properties of thymic cortical and medullary compartments are defined by highly specialised thymic epithelial cells (TEC). For example, in the medulla heterogenous medullary TEC (mTEC) contribute to the enforcement of central tolerance by supporting deletion of autoreactive (...) T‐cell clones, thereby counterbalancing the potential for random T‐cell receptor generation to contribute to autoimmune disease. Recent advances have further shed light on the pathways and mechanisms that control heterogeneous mTEC development and how differential mTEC functionality contributes to control self‐tolerant T‐cell development. Here we discuss recent findings in relation to mTEC development and highlight examples of how mTEC diversity contribute to thymus medulla function. (shrink)

BackgroundEvidence suggests that organizational models that provide care interventions including patient support programs may increase patient adherence to multiple sclerosis therapies by providing tailored symptom management, informational support, psychological and/or social support, lifestyle changes, emotional adjustment, health education, and tailored coaching, thus improving patients' overall quality of life across the disease course.ObjectiveThe main objective of this study was to describe MS patients' self-reported experience of a nurse-led, telephone-based PSP and to explore its potential role in improving disease and (...) therapy management skills.MethodsSurvey data were analyzed from a subset of patients relapsing–remitting MS using interferon beta-1a already registered in the adveva® PSP from three Italian multiple sclerosis centers with a consolidated experience in RRMS disease, treatment management, and PSP programs.ResultsIn total, 244 patient data at baseline were analyzed, of which 115 had a follow-up of at least 6 months. Results from this study provide an early view into the role of this PSP in improving the patients reported overall experience regarding disease management and injectable therapy, thus potentially ameliorating treatment adherence and decreasing health care cost. Moreover, study findings confirm the role of providing a patient-focused support by addressing non-medication-related topics in the PSP consultations. Indeed, patients involved in the adveva® PSP program reported a better psychological status in the follow up as demonstrated by an increased optimism regarding their future, tolerance of disease uncertainty, and their perceived ability to benefit from external help and social support.ConclusionsAs such, it is reasonable to conclude that the involvement in the adveva® PSP and the PSP's assistance in guiding patients on proper treatment self-management techniques is of great value to patients as it might contribute to improving engagement in their health care journey in terms of perceived self-care skills, emotional coping toward the future and the unpredictability of the disease course and their general attitudes toward the injection itself, involving pain tolerance. (shrink)

Are there sex differences in pain? For experimentally delivered somatic stimuli, females have lower thresholds, greater ability to discriminate, higher pain ratings, and less tolerance of noxious stimuli than males. These differences, however, are small, exist only for certain forms of stimulation and are affected by many situational variables such as presence of disease, experimental setting, and even nutritive status. For endogenous pains, women report more multiple pains in more body regions than men. With no obvious underlying rationale, (...) some painful diseases are more prevalent among females, others among males and, for many diseases, symptoms differ between females and males. Sex differences in attitudes exist that affect not only reporting, coping, and responses to treatment, but also measurement and treatment. So many variables are operative, however, that the most striking feature of sex differences in reported pain experience is the apparent overall lack of them. On the other hand, deduction from known biological sex differences suggests that these are powerful sex differences in the operation of pain mechanisms. First, the vaginal canal provides an additional route in women for internal trauma and invasion by pathological agents that puts them at greater risk for developing hyperalgesia in multiple body regions. Second, sex differences in temporal patterns are likely to give rise to sex differences in how pain is and stimuli are interpreted, a situation that could lead to a greater variability and wider range of pains without obvious peripheral pathology among females. Third, sex differences in the actions of sex hormones suggest pain-relevant differences in the operation of many neuroactive agents, opiate and nonopiate systems, nerve growth factor, and the sympathetic system. Thus, while inductive analysis of existing data demonstrate more similarities than differences in pain experience between females and males, deductive analysis suggests important operational sex differences in its production. (shrink)

According to immunology’s prevailing paradigm, immunity is based on self/nonself discrimination and thus requires a construction of identity. Two orientations vie for dominance: The original conception, conceived in the context of infectious diseases, regards the organism as insular and autonomous, an entity that requires defense of its borders. An alternate view places the organism firmly in its environment in which both benign and onerous encounters occur. On this latter relational account, active tolerance allows for cooperative relationships with other organisms (...) in the larger ecological economy. These contending orientations —one derived from biomedicine and the other from the ecological sciences— have drawn the attention of social scientists and culture critics. On the one hand, feminists have portrayed immune theory as based upon borrowed social notions of identity that reflect male aggressive values and thus distort more balanced accounts of immunity; and, on the other hand, other commentary projects immune theory as a framework in which analysis of Western societies putatively reveals analogous patterns of ‘self’ and ‘other’ interactions, where autoimmunity and immunization are understood as expressions of the insular understanding of identity. Here, a meta-interpretation is presented that shows how these critiques place the immune self on a spectrum stretching from its formulation as an autonomous agent, a modernist conception of the independent individual, to a postmodern portrayal in which this conception of selfhood has been deconstructed. Accordingly, immunology is drawn into a wide-ranging debate about agency, where differing interpretations of immunity serves as a template in which competing understandings of human social intercourse is modeled.Según el paradigma dominante en inmunología, la inmunidad está basada en la discriminación entre yo/noyo y requiere, por tanto, una construcción de la identidad. Dos orientaciones compiten por dominar: la concepción original, concebida en el contexto de las enfermedades infecciosas contempla al organismo como aislado y autónomo, como una entidad que necesita defender sus fronteras. Una visión alternativa sitúa firmemente al organismo en su entorno, en el cual suceden tanto encuentros beneficiosos como costosos. En este enfoque relacional, la tolerancia activa permite relaciones cooperativas con otros organismos en una economía ecológica más amplia. Estas orientaciones en liza —una derivada de la biomedicina y otra de las ciencias ecológicas— han llamado la atención de los científicos sociales y de los críticos de la cultura. Por una parte, el feminismo ha descrito la teoría inmunológica como basada en nociones sociales prestadas de identidad que reflejan los valores agresivos del macho y que, de este modo, impiden una explicación más equilibrada de la inmunidad. Por otra parte, otro comentario proyecta la teoría inmunológica como un marco en el que el análisis de las sociedades occidentales revela aparentemente patrones análogos de interacciones ‘yo’ y ‘otros’, en las que la autoinmunidad y la inmunización son entendidas como expresiones de la comprensión insular de la identidad. Se ofrece aquí una meta-representación que muestra cómo estas críticas sitúan al yo inmune en un espectro que va desde su formulación cómo un agente autónomo, una concepción modernista del individuo independiente, a una visión postmoderna en la que esta concepción de la identidad ha sido deconstruida. De acuerdo con esto, la inmunología recoge un amplio debate sobre la agencia en el que diferentes interpretaciones de la inmunidad sirven como molde en el que se modelan comprensiones competidoras de la comprensión de las relaciones sociales humanas. (shrink)

Starting dialysis at an advanced age is a clinical challenge and an ethical dilemma. The advantages of starting dialysis at “extreme” ages are questionable as high dialysis-related morbidity induces a reflection on the cost- benefit ratio of this demanding and expensive treatment in a person that has a short life expectancy. Where clinical advantages are doubtful, ethical analysis can help us reach decisions and find adapted solutions. Mr. H is a ninety-year-old patient with end-stage kidney disease that is no (...) longer manageable with conservative care, in spite of optimal nutritional management, good blood pressure control and strict clinical and metabolic evaluations; dialysis is the next step, but its morbidity is challenging. The case is analysed according to principlism (beneficence, non-maleficence, justice and respect for autonomy). In the setting of care, dialysis is available without restriction; therefore the principle of justice only partially applied, in the absence of restraints on health-care expenditure. The final decision on whether or not to start dialysis rested with Mr. H (respect for autonomy). However, his choice depended on the balance between beneficence and non-maleficence. The advantages of dialysis in restoring metabolic equilibrium were clear, and the expected negative effects of dialysis were therefore decisive. Mr. H has a contraindication to peritoneal dialysis (severe arthritis impairing self-performance) and felt performing it with nursing help would be intrusive. Post dialysis fatigue, poor tolerance, hypotension and intrusiveness in daily life of haemodialysis patients are closely linked to the classic thrice-weekly, four-hour schedule. A personalized incremental dialysis approach, starting with one session per week, adapting the timing to the patient’s daily life, can limit side effects and “dialysis shock”. An individualized approach to complex decisions such as dialysis start can alter the delicate benefit/side-effect balance, ultimately affecting the patient’s choice, and points to a narrative, tailor-made approach as an alternative to therapeutic nihilism, in very old and fragile patients. (shrink)

ABSTRACT Anthony Fauci, an infectious disease expert in the White House's coronavirus task force, is challenged to offer responsible public communication of science despite working under a habitual liar who has no tolerance for criticism or dissent. Fauci manages this rhetorical exigence by using strategic ambiguity, the topos of the honest broker, dissociation, and a narrative that constrains executive decision making.

Working memory is a cognitive process that involves maintaining and manipulating information for a short period of time. WM is central to many cognitive processes and declines rapidly with age. Deficits in WM are seen in older adults and in patients with dementia, schizophrenia, major depression, mild cognitive impairment, Alzheimer’s disease, etc. The frontal, parietal, and occipital cortices are significantly involved in WM processing and all brain oscillations are implicated in tackling WM tasks, particularly theta and gamma bands. The (...) theta/gamma neural code hypothesis assumes that retained memory items are recorded via theta-nested gamma cycles. Neuronal oscillations can be manipulated by sensory, invasive- and non-invasive brain stimulations. Transcranial alternating-current stimulation and repetitive transcranial magnetic stimulation are frequency-tuned non-invasive brain stimulation techniques that have been used to entrain endogenous oscillations in a frequency-specific manner. Compared to rTMS, tACS demonstrates superior cost, tolerability, portability, and safety profile, making it an attractive potential tool for improving cognitive performance. Although cognitive research with tACS is still in its infancy compared to rTMS, a number of studies have shown a promising WM enhancement effect, especially in the elderly and patients with cognitive deficits. This review focuses on the various methods and outcomes of tACS on WM in healthy and unhealthy human adults and highlights the established findings, unknowns, challenges, and perspectives important for translating laboratory tACS into realistic clinical settings. This will allow researchers to identify gaps in the literature and develop frequency-tuned tACS protocols with promising safety and efficacy outcomes. Therefore, research efforts in this direction should help to consider frequency-tuned tACS as a non-pharmacological tool of cognitive rehabilitation in physiological aging and patients with cognitive deficits. (shrink)

Aim: The presence of noise in urban environments is rarely considered a factor that causes damage to the environment. The primary generating source is transportation means, with vehicles being the ones that affect cities the most. Traffic noise has a particular influence on the quality of life of those who are exposed to it and can cause health alterations ranging from annoyance to cardiovascular diseases. This study aims to describe the relationship between the traffic noise level and the perceived annoyance (...) in the inhabitants of a city on the Northern Border of Mexico. The work carried out in a city represents the vulnerability characteristics: economic, social, and migratory of its sizable portion of the inhabitants. Due to that, it is impossible to identify precisely the number of residents as the number of vehicles in circulation.Methods: The streets and avenues with an annual average daily traffic of more than 1,000 vehicles were considered for the measurement of traffic noise. The equipment used was a vehicle gauge with non-invasive speed radar; type I integrating sound level meters, with their respective gauges and tripods. A questionnaire was applied to people living within 250 m of the streets and avenues in which the noise was measured.Results: The noise measurement found a parameter of LAeq estimated for 12 h during the day, exceeding 70 dBA. The data received from the questionnaire were statistically tested by using Pearson's correlation tests. A total number of 2,350 people were participated, of whom 1,378 were women and 972 were men. The age of participants is ranged from 18 to 75 years. The overall perception of traffic noise annoyance identified that 1,131 participants responded “Yes” as they considered the noise annoying. Participants who responded “No” as well as those who responded “Do not know” resulted in a total of 1,219 people.Conclusion: The results show that the population is desensitized to traffic noise and does not perceive it as an annoyance. The flow of vehicles and the type of vehicles are the significant factors for the propagation and increase in the traffic noise levels. Women present a considerable appreciation of traffic noise perception instead of younger people who demonstrate a higher tolerance to high-level exposure. This reflects the lack of information of the population around the noise problem and its effects. (shrink)

James E Cooper¹, Uwe Christians², Alexander C Wiseman¹¹Division of Renal Diseases and Hypertension, Transplant Center, ²iC42 Integrated Solutions in Systems Biology for Clinical Research and Development, University of Colorado Denver, Aurora, CO, USA: Everolimus is a novel target of rapamycin -I analog that has recently been approved in combination with cyclosporine A and steroids for use in the prevention of organ rejection in kidney transplant recipients. Compared with rapamycin, everolimus is characterized by a shorter half-life and improved bioavailability. Prior to (...) US Food and Drug Administration approval, a number of Phase II and III clinical trials were undertaken to evaluate the effectiveness of everolimus in combination with calcineurin inhibitors for preventing acute rejection and promoting allograft survival in kidney transplant recipients. In this report, we review the pharmacokinetic properties of everolimus, the clinical efficacy studies that led to its approval for use in kidney transplantation, as well as reported data on patient safety and tolerability associated with its use.Keywords: mTOR inhibitors, kidney transplantation, everolimus. (shrink)

Chronic pain affects a large part of the population causing functional disability, being often associated with coexisting psychological disorders, such as depression and anxiety, besides cognitive deficits, and sleep disturbance. The world elderly population has been growing over the last decades and the negative consequences of chronic pain for these individuals represent a current clinical challenge. The main painful complaints in the elderly are related to neurodegenerative and musculoskeletal conditions, peripheral vascular diseases, arthritis, and osteoarthritis, contributing toward poorly life quality, (...) social isolation, impaired physical activity, and dependence to carry out daily activities. Organ dysfunction and other existing diseases can significantly affect the perception and responses to chronic pain in this group. It has been proposed that elderly people have an altered pain experience, with changes in pain processing mechanisms, which might be associated with the degeneration of circuits that modulate the descending inhibitory pathways of pain. Aging has also been linked to an increase in the pain threshold, a decline of painful sensations, and a decrease in pain tolerance. Still, elderly patients with chronic pain show an increased risk for dementia and cognitive impairment. The present review article is aimed to provide the state-of-art of pre-clinical and clinical research about chronic pain in elderly, emphasizing the altered mechanisms, comorbidities, challenges, and potential therapeutic alternatives. (shrink)

What is the role and value of pleasure in addiction? Foddy and Savulescu have claimed that substance use is just pleasure-oriented behavior. They describe addiction as "strong appetites toward pleasure" and argue that addicts suffer in significant part because of strong social and moral disapproval of lives dominated by pleasure seeking. But such lives, they claim, can be autonomous and rational. The view they offer is largely in line with the choice model and opposed to a disease model of (...) addiction. Foddy and Savulescu are sceptical of self-reports that emphasize the ill effects of addiction such as loss of family and possessions, or that claim an absence of pleasure after tolerance sets in. Such reports they think are shaped by social stigma which makes available a limited set of socially approved addiction narratives. We will not question the claim that a life devoted to pleasure can be autonomously chosen. Nor do we question the claim that the social stigma attached to the use of certain drugs increases the harm suffered by the user. However our interviews with addicts reveal a genuinely ambivalent and complex relationship between addiction, value, and pleasure. Our subjects did not shy away from discussing pleasure and its role in use. But though they usually valued the pleasurable properties of substances, and this played that did not mean that they valued an addictive life. Our interviews distinguished changing attitudes towards drug related pleasures across the course of substance use, including diminishing pleasure from use over time and increasing resentment at the effects of substance use on other valued activities. In this paper we consider the implications of what drug users say about pleasure and value over the course of addiction for models of addiction. Well don't get me wrong, I love using mate. If I could use successfully I would. I'd still be using. I love using. I just don't like the shit that comes with it. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Romanian Cultural and Political IdentityDonald R. KelleyThe Journal of the History of Ideas, in collaboration with other institutions, including the Universities of Bucharest and Budapest and the Soros Foundation, recently sponsored the second in a series of international conferences being planned on topics in current intellectual history. (The first, “Interrogating Tradition,” was held at Rutgers University, 13–16 November 1997.) The Romanian conference, which was held in the Elisabeta Palace (...) in Bucharest (27–31 May 1998), was devoted to “Culture and the Politics of National Identity in Modern Romania.” Over forty scholars, mainly from Romania but some also from the U.S., France, Germany, and Hungary, gathered to discuss a variety of questions about Romanian society, past, present, and speculative future; and they were joined by at least as many visitors, especially students, from the local area and beyond.Topics discussed included politics, language, economics, historiography, religion, education, philosophy, ideologies, intelligentsia, particular intellectuals, minorities, and women (though not Gypsies or gays). Under this riot of rubrics a wide range of questions were posed in interdisciplinary fashion, with frequent, sometimes impassioned interventions. What is—was, might have been, can be—Romania? Who is a Romanian (and who not)? What is Romania’s relation to the West and the East? (And what are the “West” and the “East”?) To modernity, to modernism, to modernization? What is—has been, should be—the function of intellectuals, of political and cultural elites, in understanding the Romanian past and in setting a course for the future? What, more generally, is the role of history in answering such questions? Or is history perhaps (as Karl Krause remarked of psychoanalysis) the disease for which it claims to be the cure?Keith Hitchens’s keynote address suggested that rehashing old essentialist debates might not be productive at millennium’s end, but the conference itself could not avoid some excursions down the paths of memory and myth. For historians, Western historians anyway, Romania seems to have too many pasts. Located at the juncture of four previous empires, Romania is a mosaic, or perhaps a pandemonium, of ethnic, religious, economic, and ideological groups that can only imagine, or invent, a nationality. Geographically (and in many ways culturally) remote from the West, Romania for a long time (as Sorin Antohi remarked) lacked both a public sphere and a civil society; and suffering “a Counter-Reformation without a Reformation” (Alexandru Dutu’s phrase), it has not enjoyed a tradition of religious or ethnic toleration. Nor have either the Germans or the Jews (as Glass said) found their own unity within the changing borders of the modern Romanian state. Not until the nineteenth century did Romania develop, out of its Boyar background (as Siupiur argued), an intellectual elite that could create a modern national history and help turn “peasants into Romanians” (Antohi’s phrase); and even then this elite seemed more attracted to conservative [End Page 735] (Herder, Savigny, Burke) than to liberal views of autochthonism. Many features of Western modernity, such as Newtonian science, reached Romania late, and indeed there was a retrograde movement against liberalism under the aegis by orthodox religion. In any case this intelligentsia has been as fragmented and multiform as the Romanian past itself. True, some Romanian scholars like to posit a mainstream tradition, “excesses aside,” as one speaker put it—but how, asked another, can historians put “excesses” aside from the devastating perspective of this century?Political and cultural self-examination was the dominant theme of this conference. Nationality, said Pippidi, depends on three factors, viz., name, language, religion, and territory. The Romanian name dates from the tenth century, indicating a separation of the Roman from the Greek tradition in Wallachia; and from the seventeenth century the idea of a mainly Roman provenance was given privilege. As a language, “Romanian” was spoken in the late Middle Ages, but the first written document is dated 1521. The principal religion in Romania was and is Greek orthodox, although there are also Roman Catholic, Jewish, Islamic, and German Protestant communities, as well as the Uniate church created in the eighteenth century. As for the territory, this has been a matter of change, conflict, and confusion throughout the tragic course... (shrink)

The study of social, ethical, and political issues from a naturalistic perspective has been pervasive in social sciences and the humanities in the last decades. This articulation of empirical research with philosophical and normative reflection is increasingly getting attention in academic circles and the public spheres, given the prevalence of urgent needs and challenges that society is facing on a global scale. The contemporary world is full of challenges or what some philosophers have called ‘existential risks’ to humanity. Nuclear wars, (...) natural and/or engineered pandemics, climate change, global totalitarianism, and emergent technologies, are some of the challenges mentioned by many authors devoted to the study of long-term potential risks for the survival of the human species. However, while there are many reasons to be a pessimist about the future of humanity, there is also a lot of ink wasted in showing that the world today is far better than we had in the past and also that there have been many instances of social and moral progress in the last centuries. Some authors have even claimed that “we have made more progress over the last 100 years than in the first 100,000”. According to ‘our world in data’, some of the most relevant advances of humanity in the last centuries have to do with the reduction of poverty and/or inequality, better health and security, the decline of violence and war, and the development of democracy and institutional mechanisms to guarantee individual freedom and rights. Yet, there is a more concrete concern that our world faces nowadays, and requires a particularly detailed analysis. In a few words, the advance in information and communication technologies, the huge volume of people migration because of prevalent instances of global inequality, and the reality of an interconnected world that just mirrors an extensive history of massive human intergroup relations open the question about the feasibility of social and moral progress in the contexts of diverse, multicultural, and unequal societies. This makes it crucial to reflect not only on whether human societies may keep advancing on a path of social progress, but how this can be achieved by addressing the challenges of inequality and potential intergroup conflict. This concern closely relates to the further consolidation of democratic values and the achievement of a more generalized consideration of the equal moral value of human individuals far from group, ethnic, or collective distinctions. This vision of progress follows the moral convictions that have been considered right and worthy to be pursued by most ethical theories explored by philosophers and social scientists so far. This work aims to contribute to the study of the mechanisms and feasibility of social and moral progress grounded on the precept of human equality and is guided by the idea that social and moral progress in a plural world requires the accomplishment of a more democratic and tolerant society. These forms of progress have already been defined by philosophers Allen Buchanan and Russel Powell as inclusivist forms of moral progress. According to these authors, inclusivist moral progress is featured by the transformation of moral judgments, motivations, and norms guided by the rejection of “group-based restrictions on moral standing and moral status” (2018). The work of Buchanan and Powell is fundamental for the argumentation developed in this work since they have pioneered a more complex debate in the field of evolutionary social sciences and philosophical anthropology. In brief, these authors have inquired how human nature, conceptualized by the advances in evolutionary thinking and the empirical sciences, is related to our moral convictions and the possibilities that we have to establish certain forms of social and moral progress. The work of Buchanan and Powell contributes to the debate on moral progress by incorporating empirically-informed concepts and arguments. With this objective in mind, they develop their discussion around a generalized tension between exclusivist and inclusivist forms of moral progress. This tension revolves around the question of whether and to what extent human moral concerns, motivations, and norms, are limited or bounded by social identities, group thinking, or collective values. This question is at the center of this work. In other words, I aim to answer whether and to what extent the nature of our social and moral cognition hinders or enables the development of inclusivist forms of morality and moral progress. As I mentioned so far, the distinction between exclusivist and inclusivist forms of morality has a practical implication and facilitates the reflection on the mechanisms and feasibility of concrete forms of progress based on the precept of human equality, which is the road to progress that we should follow according to most ethical theories. The distinction between exclusivist and inclusivist morality is not used here as a form of summarizing highly divergent descriptive approaches to morality, but as a way to address the practical implications of morality research, particularly around the question of the feasibility of social forms of progress based on the precept of equality and tolerance. My objective then has less to do with offering a conceptualization of human morality or with the proposition of a new ethical perspective. Instead, I aim to identify, from an empirically informed perspective, what enables the achievement of egalitarian forms of social progress, to subsequently offer a normative reflection about what we should do if we want to accomplish such inclusivist forms of progress. This task is of great relevance, having in mind that some theoretical proposals on the matter have claimed that human prosocial behavior and morality are constrained by exclusivist fixed tendencies as a product of our evolutionary history. According to these views, human morality is a group-centered cognitive and behavioral expression that has severe limits in its scope and extent, which hinders in the end the emergence of inclusivist forms of moral concerns and behaviors. These claims align with the philosophical intuition about the ‘dissociation of empathy’, or the fact that human individuals tend to express empathy and sympathy preferably for members of their group whereas their empathic and moral concern and recognition for outgroup individuals tend to be reduced or eliminated in real-life social interactions. Multiple theorists have expressed, however, that these assumptions are wrong for empirical and philosophical reasons, which results in a serious challenge to the conception of human morality as exclusivist by nature. Furthermore, simple intuition and practical experience constantly show us that human individuals can develop and endorse a broad spectrum of moral considerations and adopt an arguably inclusivist stance concerning the kind of persons or agents that deserve moral concern. Moreover, and adopting a historical perspective, the expansion of cultural and commercial exchanges, the consolidation of democracy, the development of welfare states, or the emergence of institutions based on the concept of universal human rights, have partially driven human progress based on the impartial concern for the well-being of persons. These historical instances of cultural evolution and institutional design have shown that it is feasible to promote behaviors and attitudes grounded in impersonal prosocial and inclusivist principles. This optimistic perspective, however, still begs the question of the exact relationship between social, cultural, and historical contexts, and the emergence of certain behavioral expressions of inclusivist morality. This is crucial since a great number of human individuals around the world still do not make part of these instances of social progress, and some authors have suggested that such instances of social and moral progress are particularly favored by the contexts of the WEIRD world, that is the world of Western, Educated, Industrialized, Rich, and Democratic societies. Some of these approaches consider moral inclusivity a ‘luxury good’ and follow the ‘dependency thesis’ according to which the expression of moral inclusivity depends on the presence of very concrete material conditions that trigger inclusivist and impersonal prosocial tendencies that human beings are not able to express in threatening contexts without physical security. This thesis is problematic for various reasons and has led to incomplete explanations about the enabling and causal factors of inclusivist moral progress, as well as unsatisfactory suggestions about what we should do to foster the accomplishment of more generalized instances of progress based on inclusivist concerns. In an attempt to contribute to this debate, the main objective of this thesis is to offer an alternative proposal about the nature of human morality and a more detailed reflection on what we should do if we want to further accomplish such instances of progress. More precisely, this work adopts a particular developmental and constructivist vision of human morality to answer the question of how feasible it is to reach generalized forms of social progress based on the precepts of moral inclusivity. Furthermore, it offers some ideas about what are the most adequate and favorable conditions to foster such progress both at the individual and the collective level. At this point, a preliminary clarification of some starting points is necessary. In the first place, and contrary to what other authors have proposed when debating moral progress from an empirically-based approach, my perspective adopts a radical developmental and constructivist perspective, following particularly the conceptual and empirical ideas of the social-domain theory in moral psychology. From this perspective, morality is a domain of normative and social knowledge that develops and emerges in human interactions. Moral concerns, judgments, and norms are not only the result of the expression of innate adaptive intuitions, nor the product of social conformity and a simple process of mirroring the normativity that communities have established to organize their social life. Human individuals, instead, construct moral concerns and judgments during their situated interactions. More specifically, the constructivist tradition claims that we need to research how moral concerns, judgments, and reasons emerge in social interactions and how human beings construct the content of their moral knowledge in the first place. Based on these ideas, morality is defined here as the result of a constructive process through which human individuals, by the means of constant interactions on a background of mutual respect and recognition, develop evaluative concerns about how we ought to treat others, and how to ‘care’ and ‘respect’ others’ well-being, needs, and vulnerabilities. This developmental-constructivist theory of human psychology contributes to an alternative understanding of the origins of moral variability and informs a very particular normative stance about the most desirable contexts needed for the urgent accomplishment of inclusivist forms of morality in contemporary societies. This is so given that the very same definition of morality adopted presupposes the feature of inclusivity. The main objective of this work is then to argue, based on a developmental perspective, what are the most favorable conditions to foster the development of moral inclusivity and what we should do to accomplish concrete instances of moral progress that truly help us to overcome our most urgent moral challenges. The whole thesis is organized as follows. In part I, I show how received visions about human social evolution have informed conceptions of morality as an adaptive function evolved to solve the challenges of cooperative life. Based on these assumptions, some theories argue that human morality is limited by the boundaries of group thinking, and always obeys the mandates of collective interests and the will of the majority. However, this conception has problematic implications from a normative and ethical perspective. The aim of Chapter 1 is to present this introductory debate in detail. In chapter 2, I consider a relevant amount of scientific evidence that helps to consolidate a more optimistic and inclusivist perspective about the starting conditions of human prosocial behavior. Later, I will summarize some ideas offered to explain the possible evolutionary mechanisms that led to the consolidation of these inclusivist capacities. However, I will also show how evolutionary theories that share the same adaptationist foundations but initially seem relevant to explain the feasibility of moral inclusivity, result incomplete when considering the complexity of moral behavior and its ethical implications. Part II is devoted to presenting a developmental alternative to the adaptationist versions around the starting conditions of morality. In this section, I first summarize the epistemological, conceptual, and empirical basis of a constructivist perspective already proposed by several authors in the last decades. This is the goal of chapter 3. More precisely, I adopt the conceptualization of morality established by the social-domain theory school and clarify its conception of the situated development of moral concerns, motivations, and norms. All these ideas are essential for my argumentation on the feasibility of inclusivist moral progress offered later. Chapter 4 provides a more detailed idea of constructivist thinking about moral development, by analyzing one particular dimension: the development of moral concerns for fairness and the sense of justice in distributive dilemmas. In Part III, I assume a constructivist perspective on morality to contribute to the philosophy of moral progress. In particular, I discuss the implications of such a perspective for the conceptualization of human moral nature and discuss what are the most favorable conditions for moral inclusivity to emerge. Answering that question is of enormous relevance since favoring the transition of human societies towards more inclusivist forms of moral concern and behavior supposes a more generalized accomplishment of our most urgent moral convictions. Previous developmental or culturally-sensible attempts to explore this issue are already on the market. As mentioned before, most authors have approached the topic by situating the cultural evolution and development of (inclusivist) moral progress in the WEIRD world. For instance, some of these authors claim that very concrete material conditions (mostly present in the Western World) have been necessary for triggering inclusivist and impersonal prosocial tendencies that human beings are not able to express in threatening contexts without physical security. Despite their interest in explaining inclusivist morality and the feasibility of inclusivist forms of progress following a naturalistic and culturally situated approach, these theories are problematic for two main reasons. In the first place, most of the authors that explain moral progress tend to focus exclusively on the consolidation of liberal values in the Western world and the underlying adoption of laws, social-epistemic practices, and public narratives about tolerance and inclusivity, as unequivocal signs of inclusivist morality. Nevertheless, there is an enormous distance between the institutional and public support of inclusivist moral values or the construction of public images of tolerance and inclusivity, and the real materialization of impersonal moralities in situated social interactions. Secondly, the variability of human moral behavior is far bigger than most of the theories in moral psychology and moral progress tend to assume. Accordingly, inclusivist and exclusivist forms of morality may develop simultaneously in similar or divergent geographical and socio-ecological environments, including those with harsh conditions such as competition for scarce resources, potential intergroup conflict, and risks of disease transmission. In addition, harsh environmental conditions are usually present in almost all societies around the globe, and the presence of socio-ecological conditions such as physical security and prosperity, predominant in highly resourced populations, do not prevent the existence of exclusivist moral tendencies. My model explores a different perspective on the relationships between cultural, institutional, and historical factors, and the situated development of human morality. This supposes a clear distinction from previous approaches to the matter since it offers a different view on what we should do to pursue further instances of inclusivist social progress. In the fifth chapter, I first analyze the proposals of some defenders of the ‘dependency’ theory. The attention is focused on the ‘Evolutionary Developmental Model’ proposed by Buchanan and Powell (2018). Based on a critique of this approach, I will argue that to explain the evolution and development of human morality in its multiple manifestations, it is essential to put focus on social interactions. This also involves a different perspective on human-environment relations that in line with a constructivist worldview makes an innovative contribution to the philosophy of moral behavior and moral progress. Later, in the sixth chapter, I will define my alternative relational view of inclusivist morality and I will offer my view on how to establish favorable conditions that make inclusivist morality possible. Complementing the constructivist approach, my conception is based on the essential role of equality and individuality and on how moral inclusivity is favored if moral concerns do not develop driven by the accomplishment of group-centered, binding, and communitarian concerns and values. In brief, my relational model suggests that the accomplishment of moral inclusivity not only depends on the overall achievement of certain levels of physical security or economic prosperity. Instead, its development is favored by transforming the interactional contexts in which moral concerns towards autonomy and individuality emerge. In arguing so, I will need to start with a critique of contemporary situated and embodied approaches in ethics. Then, I will show how societies guided by the accomplishment of group-centered values of power, dominance, and relational inequality tend to express exclusivist moral behaviors, while individualistic societies tend to be more inclusivist. Starting from this diagnosis, my final attempt is then to reflect on which are the best conditions for the moral valuation of individuality to emerge and what we should do to promote the accomplishment of moral inclusivity at the societal level. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Black Horseman Lane: A ReflectionJanet PniewskiI felt a sinking feeling in the pit of my stomach upon getting the news this particular patient, let’s call him Stan, had burned through yet another nurse case manager and it would now be my responsibility to take charge of his care. As the medical director read aloud his patient profile, “Sixty–eight year old frail appearing Caucasian male with a terminal diagnosis of...” (...) I was already formulating excuses in my head as to why I would not be able to accept this charge. However, when she finished, I dutifully replied, “Ok, I’ll give it my best shot.” At the time, I was well aware that this assignment would test my resolve and commitment to providing the same high quality compassionate [End Page 117] care to every patient, but what I did not realize was how much I would grow personally and professionally in the process.Stan was well known in the organization for being “non–compliant” and “difficult.” Through his past actions he earned the label of racist and misogynist, having zero tolerance for people whom he perceived as different from him in any way. He was profoundly disrespectful toward women and was known to abuse his animals. Having been raised in a liberal household in New Jersey, surrounded by civil rights activists, animal activists and feminists, I was genetically programmed to abhor social injustice and raised to serve as an advocate for the disenfranchised and vulnerable. Since childhood, I’ve experienced visceral reactions to acts of injustice or cruelty of any kind. The very idea of someone like Stan was appalling.I found myself assigned to Stan’s case by default. He fired his first nurse because she was African American and painted her as dishonest and incompetent. He fired his second nurse because he was male and therefore must be gay. He fired his social worker because she was overweight, which certainly meant she was lazy. He fired the chaplain because he was not Catholic and thus unworthy of having any meaningful spiritual discourse. He would not accept the recommendations of our medical director because she was a woman. His family had given up on him a long time ago. His wife left him shortly after his youngest child had gone off to college, and all four of his children were estranged. Stan’s disease was progressing, despite therapy, and he was becoming too weak to care for himself at home without hospice support. His oncologist pleaded with us to give it one more try, even though we were running out of staff. These people that Stan had dismissed so unpleasantly were my colleagues and friends. The first nurse Stan dismissed served as my ever patient and knowledgeable preceptor when I was new to hospice and fumbling my way through unfamiliar protocols. The second nurse Stan rejected was a dedicated colleague and devoted friend, supporting me through several life challenges. I had witnessed our chaplain, judged as unworthy by Stan, tirelessly provide comfort to patients, family members and staff members in the darkest of hours. I knew them all as well–meaning, competent and compassionate team members and Stan’s disrespect for them offended me.Apparently, Stan was offended as well. His oncologist revealed to us that Stan was angered by his referral to hospice. He felt abandoned. I was Stan’s last hope; however, he didn’t see it that way. Neither Stan nor I was enthusiastic about our impending partnership.Stan was an engineer by trade, and apparently very successful in business. He lived on a sprawling plantation located at the end of his private road, which he named Black Horseman Lane. As I turned down the drive, aware of his reputation as a bigot, I contemplated how Stan might have arrived at this name. With the assistance of my smartphone, I was able to ascertain that there was, indeed, a Black Horseman of the Apocalypse, which was associated with famine. Delving further, into Wikipedia, my interpretation was that the Black Horseman’s famine decimated the grain crop, sparing the olive groves and grapevines, driving up the price of grain but leaving oil and wine... (shrink)

Regulatory approach to the right to abortion in Europe is diverse and basically related to the issue of when the right to life begins and how this question is reflected in national legislation. Such an approach and diversity is tolerated by the European Court of Human Rights, but only if some specific standards and criteria formulated in the jurisprudence of the European Court of Human Rights are reflected in national legislation. Research of the Lithuanian legal acts conducted in the light (...) of the jurisprudence of the Court shows that they are not in accordance with the jurisprudence of the European Court of Human Rights and the solutions are therefore suggested. The aim of the article is to systematically analyse the Lithuanian legal acts regulating issues of abortion and to identify the existing problems and provide suggestions as to how to solve those problems with the help of the jurisprudence of the European Court of Human Rights in abortion cases. Analysis of the Lithuanian legal acts reveals that the existing legal regulation and practice is confusing and ambiguous. Abortion questions are regulated in Lithuania by means of secondary legislation, namely by order of the Health Minister which is more than 15 years old, and the classification of diseases dangerous to woman’s health and life is based on international classification that is invalid. The order is not in reconciled with the Lithuanian criminal law. Some other ambiguities and problems are identified in the article. Abortion on a woman’s request in Lithuania is possible by the end of the 12 week of pregnancy and during the entire pregnancy, if it causes danger to woman’s health and life. The Lithuanian legislator requires that both conditions – danger to woman’s health and life – are met in order to terminate pregnancy what is unnecessary and sometimes even confusing. The author suggests providing two separate bases for abortion – danger to woman’s life or health. Foetus problems – if a foetus is irreversibly damaged or suffering from an incurable life-threatening disease, it is not a separate basis for abortion in Lithuania, however those abnormalities of the foetus are related to the health and life of a pregnant woman. In the opinion of the author, looking into the practice of the other EU countries, it is better to provide a separate ground for abortion because of abnormalities of the foetus. The basic problem in Lithuania that is similar in Poland and in Ireland is that there is no clear procedure in case a pregnant woman is not satisfied with the decision of the medical commission regarding the question of her abortion or if the opinion of members of the commission is diverse – no time guidance or appeal institution is provided. (shrink)

Oncological treatments are responsible for many of the physical changes associated with cancer. Because of this, cancer patients are at high risk of developing mental health problems. The aim of this study is to propose an innovative Virtual Reality training that uses a somatic technique to create a bridge with the bodily dimension of cancer. After undergoing a psycho-educational procedure, a combination of exposure, out-of-body experience, and body swapping will gradually train the patient to cope with cancer-related difficulties, increasing stress (...) tolerance, and patient empowerment. The most engaging step of this advanced form of Stress Inoculation Training is the body swapping experience, which will guide the patient in embodying a resilient cancer patient who is facing similar difficulties. Through the VR ability to simulate the human brain functioning, and the potential of embodiment to hook to the somatic dimension of illness, we expect that once the concepts endured through the patient’s experience of resilience are triggered, the patient will be more prone to implement functional coping strategies in real life, reaching empowerment and adjusting to the post-treatment difficulties. When the scenarios are built and the training tested, our intervention could be used to support patients with different oncological diseases and who are treated in different cancer hospitals, as well as patients with other non-oncological problems. Future research should focus on using our paradigm for other clinical populations, and supporting cancer patients in coping with different distressing situations. (shrink)