Maladie maniacodépressive et créativité

On the basis of pathological, empirical-statistical and experimental investigations of grand creatives and of normal patients of the manic-depressive spectrum, as well as leaning on my own observations comparing mental states and stiles of behaviour, the relationship between manicdepressive illness and creativity is investigated. With respect to cognitive stiles in manic-depressives as well as in creatives, the significance of tolerance respective intolerance of ambiguity in both groups is particularly informative. The significance of creativity as an autopoiesis in the context of the structuring of identity in manic-depressives not only illuminates the essence of the manic-depressive illness and of creativity, but can also provide us with basics for a therapy oriented to creativity in these patients.     

A Statistical Physics View of Pitch Fluctuations in the Classical Music from Bach to Chopin: Evidence for Scaling

Because classical music has greatly affected our life and culture in its long history, it has attracted extensive attention from researchers to understand laws behind it. Based on statistical physics, here we use a different method to investigate classical music, namely, by analyzing cumulative distribution functions (CDFs) and autocorrelation functions of pitch fluctuations in compositions. We analyze 1,876 compositions of five representative classical music composers across 164 years from Bach, to Mozart, to Beethoven, to Mendelsohn, and to Chopin. We report that the biggest pitch fluctuations of a composer gradually increase as time evolves from Bach time to Mendelsohn/Chopin time. In particular, for the compositions of a composer, the positive and negative tails of a CDF of pitch fluctuations are distributed not only in power laws (with the scale-free property), but also in symmetry (namely, the probability of a treble following a bass and that of a bass following a treble are basically the same for each composer). The power-law exponent decreases as time elapses. Further, we also calculate the autocorrelation function of the pitch fluctuation. The autocorrelation function shows a power-law distribution for each composer. Especially, the power-law exponents vary with the composers, indicating their different levels of long-range correlation of notes. This work not only suggests a way to understand and develop music from a viewpoint of statistical physics, but also enriches the realm of traditional statistical physics by analyzing music.     

Epigenetics and the power of art

This review presents an epigenetic view on complex factors leading to development and perception of "genius." There is increasing evidence which indicates that artistic creativity is influenced by epigenetic processes that act both as targets and mediators of neurotransmitters as well as steroid hormones. Thus, perception and production of art appear to be closely associated with epigenetic contributions to physical and mental health.     

Driving Precision Medicine through Proteomics and Metabolomics - 12th Central and Eastern European Proteomic Conference (CEEPC), Bucharest,Romania

As Romanians prepared to celebrate 100 years of the '‘Great Unification of 1918?' which united all provinces into one Romania, the 12^th Central and Eastern European Proteomic Conference (CEEPC) jointly with the 39^th Anniversary of the Institute of Cellular Biology and Pathology '‘N. Simionescu’' (ICBP-NS), held their inaugural meeting at the Romanian Academy in Bucharest – a national forum of highest scientific recognition. With an exciting theme entitled, ‘Advances in Proteomics and Progress in Precision Medicine’, delegates gathered to debate Precision medicine’s revolution in diagnosis and treatment, which now accounts for predictive, preventative, and targeted treatment strategies with informed decisions according to individual’s unique clinical, molecular and genetic profile. Proteomics has a pivotal role to play in furthering precision health and medicine for the benefit of mankind. To this end, CEEPC continues to drive advances in proteomics, metabolomics, and diseases as well as raising awareness of pressing global humanitarian and health-care issues including mental health diseases, aging, chronic diseases, global epidemics and environmental issues. Today, CEEPC is a well-recognized major annual conference with a focused vision and a highly valued ideology as it continues to propagate scientific, medical and proteomic collaborations whilst expanding as more Eastern European countries prepare to join.     

Aggregated proteins in schizophrenia and other chronic mental diseases

Chronic mental diseases (CMD) like the schizophrenias are progressive diseases of heterogenous but poorly understood biological origin. An imbalance in proteostasis is a hallmark of dysfunctional neurons, leading to impaired clearance and abnormal deposition of protein aggregates. Thus, it can be hypothesized that unbalanced proteostasis in such neurons may also lead to protein aggregates in schizophrenia. These protein aggregates, however, would be more subtle then in the classical neurodegenerative diseases and as such have not yet been detected. The DISC1 (Disrupted-in-schizophrenia 1) gene is considered among the most promising candidate genes for CMD having been identified as linked to CMD in a Scottish pedigree and having since been found to associate to various phenotypes of CMD. We have recently demonstrated increased insoluble DISC1 protein in the cingular cortex in approximately 20% of cases of CMD within the widely used Stanley Medical Research Institute Consortium Collection. Surprisingly, in vitro, DISC1 aggregates were cell-invasive, i.e., purified aggresomes or recombinant DISC1 fragments where internalized at an efficiency comparable to that of α-synuclein. Intracellular DISC1 aggresomes acquired gain-of-function properties in recruiting otherwise soluble proteins such as the candidate schizophrenia protein dysbindin. Disease-associated DISC1 polymorphism S704C led to a higher oligomerization tendency of DISC1. These findings justify classification of DISC1-dependent brain disorders as protein conformational disorders which we have tentatively termed DISC1opathies. The notion of disturbed proteostasis and protein aggregation as a mechanism of mental diseases is thus emerging. The yet unidentified form of neuronal impairment in CMD is more subtle than in the classical neurodegenerative diseases without leading to massive cell death and as such present a different kind of neuronal dysfunctionality, eventually confined to highly selective CNS subpopulations.     

Organismic sets. Scientific creativity,its spread and applications

The phenomenon of mental creativity is considered from the standpoint of the theory of organismic sets, developed by the author in a series of previous publications. It is shown how the differences in creativity between different individuals may be interpreted on this basis, and why extreme creativity is rare. A parallel interpretation for facility in observation is given, and it is shown why facility in creativity and observation is much rarer than either individual facility. A further conclusion is drawn regarding the deducibility of the laws of nature by purely logical means.     

circRNA: Regulatory factors and potential therapeutic targets in inflammatory dermatoses

The skin is the largest organ of the human body and acts as the first line of defence against injury and infection. Skin diseases are among the most common health problems and are associated with a considerable burden that encompasses financial, physical and mental consequences for patients. Exploring the pathogenesis of skin diseases can provide insights into new treatment strategies. Inflammatory dermatoses account for a large proportion of dermatoses and have a great impact on the patients'' body and quality of life. Therefore, it is important to study their pathogenesis and explore effective treatment. Circular RNAs (circRNAs) are a special type of RNA molecules that play important regulatory roles in several diseases and are involved in skin pathophysiological processes. This review summarizes the biogenesis, properties and functions of circRNAs as well as their roles in the pathogenesis of inflammatory dermatoses, including psoriasis, lupus erythematosus, atopic dermatitis, lichen planus and severe acne and their potential as therapeutic targets.     

Who's afraid of a cognitive neuroscience of creativity?

This article has two goals. First, the ideas outlined here can be seen as a sustained and disciplined demolition project aimed at sanitizing our bad habits of thinking about creativity. Apart from the enormous amount of fluff out there, the study of creativity is, quite unfortunately, still dominated by a number of rather dated ideas that are either so simplistic that nothing good can possibly come out of them or, given what we know about the brain, factually mistaken. As cognitive neuroscience is making more serious contact with the knowledge base of creativity, we must, from the outset, clear the ground of these pernicious fossil traces from a bygone era. The best neuroimaging techniques help little if we don't know what to look for. Second, as an antidote to these theoretical duds, the article offers fresh ideas on possible mechanisms of creativity. Given that they are grounded in current understanding of cognitive and neural processes, it is hoped that these ideas represent steps broadly pointing in the right direction. In the end, the fundamental question we must ask ourselves is what, exactly, are the mental processes--or their critical elements--that yield creative thoughts.     

Wood Densitometry in 17th and 18th Century Dutch,German, Austrian and French Violins,Compared to Classical Cremonese and Modern Violins

Classical violins produced by makers such as Antonio Stradivari and Guarneri del Gesu have long been considered the epitome of the luthier''s art and the expressive tool of choice for the most celebrated violinists. It has been speculated these makers had access to wood that was unique in some way and that this was responsible for their acclaimed tonal characteristics. In an attempt to discern whether the above conjecture is true, we analyzed 17 modern and classical Dutch, German, Austrian and French violins by wood densitometry using computed tomography and correlated these results with our previous study of modern and Cremonese violins; in all studying 30 instruments of the violin family. In order to make this comparison possible we developed methods to cross calibrate results from different CT manufacturers using calibration wood pieces. We found no significant differences in median densities between modern and classical violins, or between classical violins from different origins. These results suggest that it is unlikely classical Cremonese makers had access to wood with significantly different wood density characteristics than that available to contemporaneous or modern makers.     

Selective inhibition of the interaction of C1q with immunoglobulins and the classical pathway of complement activation by steroids and triterpenoids sulfates

Since undesirable activation of the complement system through the classical pathway is associated with tissue damage and other pathologic proinflammatory consequences at ischemia/reperfusion injury, autoimmune diseases, and rejection of allo- and xenografts, creation of selective inhibitors of the classical pathway leaving the alternative pathway intact is of great importance. Classical pathway is triggered by binding of its recognizing unit, protein C1q, to a number of targets like antibodies, pentraxins, apoptotic cells, and others. In order to obtain inhibitors blocking the first step of the classical cascade, synthesis of sulfates of steroids (Delta(5)-3beta-hydroxycholenic, Delta(5)-3beta-hydroxyetiocholenic, deoxycholic, and cholic acids) and triterpenoids (betulin, 20,29-dihydro-20,29-dichloromethylenbetulin, betulinic, ursolic, and oleanolic acids) has been performed. Testing of the compounds in classical pathway inhibition assay has displayed derivatives of triterpenoid betulin (betulin disulfate and betulinic acid sulfate) to be the most potent inhibitors. Further studies of the two compounds established that their activity to inhibit the classical pathway had been due to their capability to block the interaction of C1q with antibodies. Betulin disulfate and betulinic acid sulfate have shown weak inhibition of the alternative route of activation, what makes them promising inhibitors for the selective suppression of the classical complement pathway at the earliest possible level as well as perspective agents for blocking the interaction of C1q with its other targets.     

EPIDEMIOLOGY IN THE SOCIAL SCIENCES

The techniques and principles of epidemiology, so successfully utilized in the study and control of communicable diseases, should be applied to other mass phenomena in the community.The local health officer should apply them in his “diagnosis” of the sicknesses of his organized community.Epidemiological methods have been used to study mental diseases as well as chronic diseases, and an experiment in using epidemiological methods on the county level to study psychosocial disorders has been carried out.The impact of psychosocial episodes on somatic diseases is now generally accepted and well documented. Individual practitioners of medicine are becoming more interested in the significance of social tensions on the health of their patients.Public health physicians, specialists in preventive medicine, are the best equipped by training and experience to take the leadership in the application of epidemiological methods to sociomedical problems and are in a unique position to assist their colleagues in the private practice of medicine in providing modern helpful and meaningful health protection to their patients.Organized medicine might well become more cognizant of the sociological changes taking place in the nation as they relate to health and assume the responsibility for aggressive leadership in the anticipation of and the solution of these problems.     

Health and the city: physical health and mental health

In France, city size has very little bearing on the mortality rate as a function of age and life expectancy and it is in large cities that these indicators are the most favorable. No increase in maternal or infant mortality rates or deaths due to cancers has been observed in large cities. The lower mortality rate linked to respiratory and cardiovascular diseases in large urban areas contradicts the fears concerning the impact of air pollution. Deaths linked to lifestyle are less frequent in big cities, which could be due to social structures (socio-professional level: the proportion of white-collar workers and professionals is higher in bigger cities than in the suburbs or small cities). However, although the overall mortality rate is lower, it should be emphasized that there is in large cities a greater incidence of sexually transmitted diseases, AIDS and certain infectious diseases (because of social diversity and the fact that certain individuals seeking anonymity and marginality are drawn to large cities). In terms of mental health, the breakdown of family structures, instability, unemployment, the lack of parental authority and failing schools render adolescents vulnerable and hinder their social integration. When the proportion of adolescents at risk is high in a neighborhood, individual problems are amplified and social problems result. In order to restore mental and social health to these neighborhoods, ambitious strategies are necessary which take into account family and social factors as well as environmental ones. At the present time, when physical health is constantly improving, the most pressing problems are those related to lifestyle and mental health which depend for a large part on social factors.     

The cognitive and identity development of twins at 16 years of age: a follow-up study of 32 twin pairs.

This is a follow up study of twins within the Stockholm area, including 32 families and their twins attending grade nine. The twins have been followed from birth to 16 years of age. The main purpose of this study from its inception was to assess mental and cognitive development at different ages. Another aim was to see how the twins who were born prematurely are developing during the school ages. A third aim has been to gain a deeper insight into the relationship between co-twins and the development of their identities, which is the focus of this paper. Several ability tests have been used, as well as questionnaires about interests, attitudes toward school, and leisure activities. At the 16-year follow-up, a psychological method, the Wartegg drawing test, designed to examine identity, ego strength, dependency, ambition, anxiety, willpower, creativity, empathy and coping strategies has been used. The results indicate that it is difficult for twins to develop independence and a positive identity, as they have to emancipate themselves both from their parents and from their co-twins. Some differences in identity, anxiety and ambition were observed between female and male twins, MZ and DZ twins, preterm and fullterm twins. Prematurity, sex and zygosity no longer had any relation to cognitive development at 16 years of age.     

Models and Myths of Science: Views of the Elephant

I discuss selected philosophies of science in terms of the roleof rationalism in science and the reality status of the productsof scientific reasoning. A model is then presented in whichI argue that creativity in science involves the mental manipulationof images which are later compared to the shared empirical experienceof the scientific community. The assimilation of a scientificconcept involves a re-creation of the concept through a similarmanipulation of images and empirical experience. The processof recreation can distort the original concept. The result ofthis process of creation and recreation is neither an objectivediscovery of truth nor a subjective invention of truth but aninteractive reality composed of the inquiring human mind andan objectively unknowable nature. Since the model or myth ofscience we accept influences many aspects of the science-societyinteraction, the model I present here as well as models presentedby others ought to be carefully evaluated through the studyof the history of science.     

Alternative reality and art: the creative world of Walter Inglis Anderson

Both mental illness and creativity run in families. This observation suggests the possibility of genetic predisposition; in light of the known dynamic interrelationships among the environment, the personality, and the brain, however, it does not diminish the possibility of significant environmental influence on personal development. An examination of the biological, psychological, and social forces impacting the life of Walter Inglis Anderson (1903-1965), the South's most important artist, serves as a case in point. Anderson's upbringing, including his mother's determination that her sons become artists and her beliefs about the shamanistic role of artists in society, might have played a large part in establishing an unusual and indelible frame of reference in a family whose history insinuated the possibility of untoward outcomes.Walter Anderson's life as an artist--one who lived at times in an alternative reality--raises questions about how a different set of circumstances might have affected his mental state as well as his talent. This essay discusses some of the important relationships, events, and circumstances in Walter Anderson's life from a biopsychosocial perspective, with emphasis on psychodynamic implications of his illness and its questionable diagnosis as schizophrenia.     

Estimating the Effects of September 11th and Other Forms of Violence on the Mental Health and Social Development of New York City's Youth: A Matter of Context

This longitudinal study examines the effects of exposure to the terrorist attack of September 11th as well as exposure to other forms of community violence on change in the mental health and social attitudes of youths in New York City. Three quarters of the youths reported some form of direct exposure to the events of September 11th, and 80% reported a lot of exposure to at least 1 form of media coverage of September 11th; these rates were comparable with the citywide survey of public school students in New York City conducted by the New York City Department of Education. Results of a structural equation model that included controls for previous levels of mental health and social attitudes, as well as a range of demographic factors, indicated that direct exposure and family exposure to the event did not predict change in any mental health outcomes, but did predict change in levels of social mistrust; media exposure did predict posttraumatic stress disorder symptoms. In contrast, victimization by other forms of violence was strongly associated with change in or current levels of all of the examined mental health symptoms, whereas witnessing other forms of violence was associated with change in or levels of 3 of 4 mental health symptoms and with increased hostile attribution bias and levels of social mistrust. Implications of the results for applied developmental and public mental health strategies in response to traumatic events are discussed.     

Indications for synergetic and antagonistic effects between trace elements in the environment to human health

The objective of this work was to investigate the interactions between the level of concentrations of Ca, V Cr, Mn, Fe, Ni, Cu, Zn, As and Pb in potable water, soil, vegetation and school children hair and disease incidences of neoplasms, diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism, endocrine, nutritional and metabolic diseases, mental and behavioral disorders and diseases of the circulatory system on the population groups which are homogeneously exposed to the environmental conditions. It was found that potable water among the other investigated aspects of the physical environment has the greatest impact on the public health. The environment-disease incidence interactions have been found for all investigated diseases groups. The results reported here emphasize the importance of the observation of the mutual effects of the environmental variables on the human health for the identification of their synergetic as well as antagonistic effects.     

Phosphoproteomics of human platelets: A quest for novel activation pathways

Besides their role in hemostasis, platelets are also highly involved in the pathogenesis and progression of cardiovascular diseases. Since important and initial steps of platelet activation and aggregation are regulated by phosphorylation events, a comprehensive study aimed at the characterization of phosphorylation-driven signaling cascades might lead to the identification of new target proteins for clinical research. However, it becomes increasingly evident that only a comprehensive phosphoproteomic approach may help to characterize functional protein networks and their dynamic alteration during physiological and pathophysiological processes in platelets. In this review, we discuss current methodologies in phosphoproteome research including their potentials as well as limitations, from sample preparation to classical approaches like radiolabeling and state-of-the-art mass spectrometry techniques.     

12th international TNF conference: The good,the bad and the scientists

Members of the TNF superfamily control numerous aspects of immune defense as well as various processes of homeostasis and embryonic development. Recent advances in our knowledge of both the beneficial and the deleterious activities of these cytokines were thoroughly discussed at this conference. Participants presented new information about signaling mechanisms that these cytokines activate, with special attention to cell-death regulation, ubiquitination of signaling-proteins as a means of regulating their function, and complex systems of gene and signaling regulation. Sessions were devoted specifically to aberrations in functions of the TNF-family that contribute to the pathology of infectious, autoimmune and neurodegenerative diseases and to cancer, and to the application of our knowledge to therapy.     

Aggregated proteins in schizophrenia and other chronic mental diseases: DISC1opathies

Chronic mental diseases (CMD) like the schizophrenias are progressive diseases of heterogenous but poorly understood biological origin. An imbalance in proteostasis is a hallmark of dysfunctional neurons, leading to impaired clearance and abnormal deposition of protein aggregates. Thus, it can be hypothesized that unbalanced proteostasis in such neurons may also lead to protein aggregates in schizophrenia. These protein aggregates, however, would be more subtle then in the classical neurodegenerative diseases and as such have not yet been detected. The DISC1 (Disrupted-in-schizophrenia 1) gene is considered among the most promising candidate genes for CMD having been identified as linked to CMD in a Scottish pedigree and having since been found to associate to various phenotypes of CMD. We have recently demonstrated increased insoluble DISC1 protein in the cingular cortex in approximately 20% of cases of CMD within the widely used Stanley Medical Research Institute Consortium Collection. Surprisingly, in vitro, DISC1 aggregates were cell-invasive, i.e., purified aggresomes or recombinant DISC1 fragments where internalized at an efficiency comparable to that of α-synuclein. Intracellular DISC1 aggresomes acquired gain-of-function properties in recruiting otherwise soluble proteins such as the candidate schizophrenia protein dysbindin. Disease-associated DISC1 polymorphism S704C led to a higher oligomerization tendency of DISC1. These findings justify classification of DISC1-dependent brain disorders as protein conformational disorders which we have tentatively termed DISC1opathies. The notion of disturbed proteostasis and protein aggregation as a mechanism of mental diseases is thus emerging. The yet unidentified form of neuronal impairment in CMD is more subtle than in the classical neurodegenerative diseases without leading to massive cell death and as such present a different kind of neuronal dysfunctionality, eventually confined to highly selective CNS subpopulations.