This paper depicts e paraphernalia of an alchemist who believed in imitating creation and generating a soul thereby. The magic wands of creation are a compass and a triangular carpenter's square. They can produce the dual natured soul Ruh or Spirit symbolized as Cock and Nafs of “the soul” as snake: The real creative energy by nature is ultrasonic energy, characterizing the word of command of the creator. Ultrasonic energy can be produced by fiddle which is depicted also as such a producer. Thus all the elements necessary to imitate creation have been depicted here.
Galen's three souls incorporate previously existing ideas of soul. Soul is matter – cum – energy. As matter it is airlike, the finest by nature and as movement, like sound, the form of energy most subtle of its kind. Creator is depicted with Creation as the Cosmic egg and snake as Cosmic soul and the syllable Om, as the word incorporating creative energy. Om as humming sound is symbolized by Bees which produce such sound.
The availability of the recently completed Streptomyces coelicolor genome sequence provides a link between the folklore of antibiotics and other bioactive compounds to underlying biochemical, molecular genetic and evolutionary principles.
The world's most creative producers of natural pharmaceutical compounds are soil-dwelling bacteria classified as Streptomyces. The availability of the recently completed Streptomyces coelicolor genome sequence provides a link between the folklore of antibiotics and other bioactive compounds to underlying biochemical, molecular genetic and evolutionary principles.
Prime Matter is matter-cum-energy. The first substance identified as such was lead. When gently heated it becomes red and redness means soul or energy so that lead was potentially red or soul-like and as such dual natured. Mercury also becomes red and can return to white metal. It was thus dual natured and was the second substance recognized as Prime Matter. First lead alone and then lead and mercury were considered as the source of all metals.
This paper investigates John Dee’s relationship with two kinds of alchemist: the authorities whose works he read, and the contemporary practitioners with whom he exchanged texts and ideas. Both strands coincide in the reception of works attributed to the famous English alchemist, George Ripley (d. c. 1490). Dee’s keen interest in Ripley appears from the number of transcriptions he made of ‘Ripleian’ writings, including the Bosome book, a manuscript discovered in 1574 and believed to have been written in Ripley’s own hand. In 1583, Dee and his associate Edward Kelley left England for East Central Europe, taking with them a proportion of Dee’s vast library, including alchemical books—the contents of which would soon pique the interest of continental practitioners. Kelley used Ripley’s works, including the Bosome book, not only as sources of practical information, but as a means of furthering his own relationships with colleagues and patrons: transactions that in turn influenced Ripley’s posthumous continental reception. The resulting circulation of texts allows us to trace, with unusual precision, the spread of English alchemical ideas in the Holy Roman Empire from the late sixteenth century.
John Dee; Edward Kelley; George Ripley; Alchemy; Rudolf II; Prague; Manuscript circulation
In China the antecedent of alchemy is represented by the god of longevity emerging from the peach. The first synthetic drug, Kim-Yeh, red colloidal gold, signified gold-cum -herbal juice. Kim-Yeh=Kimiya (Arabic) =chemeia (Greek). Translated this gave Chrusozomion=Gold Ferment, specifying the drug. Rasayana was translated as Chumeia, herbal juice-incorporate and signified the art alchemy. Chemeia was Chinese and Chumeia, Indian. Originally each signified both, a drug of longevity and the art, alchemy. Finally the art of making red gold was misunderstood as the art of making gold itself
The creative processes of understanding patients’ experiences in phenomenological research are difficult to articulate. Drawing on life philosophy as represented by the Danish philosopher K.E. Løgstrup (1905–1981), this article aims to illustrate Løgstrup's thinking as a way to elaborate the creation of cognition and understanding of patients’ experiences. We suggest that Løgstrup's thoughts on sensation can add new dimensions to an increased understanding of the creative process of phenomenological research, and that his thinking can be seen as an epistemological ground for these processes. We argue with Løgstrup that sense-based impressions can facilitate an flash of insight, i.e., the spontaneous, intuitive flash of an idea. Løgstrup stresses that an “flash of insight” is an important source in the creation of cognition and understanding. Relating to three empirical phenomenological studies of patients’ experiences, we illustrate how the notions of impression and flash of insight can add new dimensions to increased understanding of the creative processes in phenomenological research that have previously not been discussed. We illustrate that sense-based impressions can facilitate creative flash of insights that open for understanding of patients’ experiences in the research process as well as in the communication of the findings. The nature of impression and flash of insight and their relevance in the creation of cognition and understanding contributes to the sparse descriptions in the methodological phenomenological research literature of the creative processes of this research. An elaboration of the creative processes in phenomenological research can help researchers to articulate these processes. Thus, Løgstrup's life philosophy has proven to be valuable in adding new dimensions to phenomenological empirical research as well as embracing lived experience.
Caring science; phenomenological philosophy; phenomenological research; Løgstrup
Concepts from cognitive neuroscience strongly suggest that the prefrontal cortex (PFC) plays a crucial role in the cognitive functions necessary for creative thinking. Functional imaging studies have repeatedly demonstrated the involvement of PFC in creativity tasks. Patient studies have demonstrated that frontal damage due to focal lesions or neurodegenerative diseases are associated with impairments in various creativity tasks. However, against all odds, a series of clinical observations has reported the facilitation of artistic production in patients with neurodegenerative diseases affecting PFC, such as frontotemporal dementia (FTD). An exacerbation of creativity in frontal diseases would challenge neuroimaging findings in controls and patients, as well as the theoretical role of prefrontal functions in creativity processes. To explore this paradox, we reported the history of a FTD patient who exhibited the emergence of visual artistic productions during the course of the disease. The patient produced a large amount of drawings, which have been evaluated by a group of professional artists who were blind to the diagnosis. We also reviewed the published clinical cases reporting a change in the artistic abilities in patients with neurological diseases. We attempted to reconcile these clinical observations to previous experimental findings by addressing several questions raised by our review. For instance, to what extent can the cognitive, conative, and affective changes following frontal damage explain changes in artistic abilities? Does artistic exacerbation truly reflect increased creative capacities? These considerations could help to clarify the place of creativity—as it has been defined and explored by cognitive neuroscience—in artistic creation and may provide leads for future lesion studies.
creativity; prefrontal cortex; frontotemporal dementia; artistic; divergent thinking
Perrow's models of organizational technologies provide a framework for analyzing clinical work processes and identifying the management structures and informatics tools to support each model. From this perspective, health care is a mixed model in which knowledge workers require flexible management and a variety of informatics tools. A Venn diagram representing the content of clinical decisions shows that uncertainties in the components of clinical decisions largely determine which type of clinical work process is in play at a given moment. By reducing uncertainties in clinical decisions, informatics tools can support the appropriate implementation of knowledge and free clinicians to use their creativity where patients require new or unique interventions.
Outside health care, information technologies have made possible breakthrough strategies for business success that would otherwise have been impossible. Can health informatics work similar magic and help health care agencies fulfill their social mission while establishing sound business practices? One way to do this would be through personalized health care. Extensive data collected from patients could be aggregated and analyzed to support better decisions for the care of individual patients as well as provide projections of the need for health services for strategic and tactical planning. By making excellent care for each patient possible, reducing the “inventory” of little-needed services, and targeting resources to population needs, informatics can offer a route to the “promised land” of adequate resources and high-quality care.
The conscious field includes not only representations about external stimuli (e.g., percepts), but also conscious contents associated with internal states, such as action-related intentions (e.g., urges). Although understudied, the latter may provide unique insights into the nature of consciousness. To illuminate these phenomena, in a new experimental paradigm [Reflexive Imagery Task (RIT)], participants were instructed to not subvocalize the names of visually-presented objects. Each object was presented for 10 s on a screen. Participants indicated whenever they involuntarily subvocalized the object name. Research has revealed that it is difficult to suppress such subvocalizations, which occur on over 80% of the trials. Can the effect survive if one intentionally generates a competing (internally-generated) conscious content? If so, this would suggest that intentional and unintentional contents can co-exist simultaneously in consciousness in interesting ways. To investigate this possibility, in one condition, participants were instructed to reiteratively subvocalize a speech sound (“da, da, da”) throughout the trial. This internally generated content is self-generated and intentional. Involuntary subvocalizations of object names still arose on over 80% of the trials. One could hypothesize that subvocalizations occurred because of the pauses between the intended speech sounds, but this is inconsistent with the observation that comparable results arose even when participants subvocalized a continuous, unbroken hum (“daaa….”) throughout the trial. Regarding inter-content interactions, the continuous hum and object name seem to co-exist simultaneously in consciousness. This intriguing datum requires further investigation. We discuss the implications of this new paradigm for the study of internally-generated conscious contents.
consciousness; mental imagery; cognitive control; ironic processing; mind wandering; involuntary processing
Understanding the creative process is essential for realizing human potential. Over the past four decades, the author has explored this subject through his brain-inspired drawings, paintings, symbolic sculptures, and experimental art installations that present myriad impressions of human creativity. These impressionistic artworks interpret rather than illustrate the complexities of the creative process. They draw insights from empirical studies that correlate how human beings create, learn, remember, innovate, and communicate. In addition to offering fresh aesthetic experiences, this metaphorical art raises fundamental questions concerning the deep connections between the brain and its creations. The author describes his artworks as embodiments of everyday observations about the neuropsychology of creativity, and its all-purpose applications for stimulating and accelerating innovation.
ArtScience; creativity; discovery; invention; innovation
Creativity requires the rapid combination and recombination of existing
mental representations to create novel ideas and ways of thinking. The
hippocampal system, through its interaction with neocortical storage sites,
provides a relational database necessary for the creation, updating,
maintenance, and juxtaposition of mental representations used in service of
declarative memory. Given this functionality, we hypothesized that hippocampus
would play a critical role in creative thinking. We examined creative thinking,
as measured by verbal and figural forms of the Torrance Tests of Creative
Thinking (TTCT), in a group of participants with hippocampal damage and severe
declarative memory impairment as well as in a group of demographically matched
healthy comparison participants. The patients with bilateral hippocampal damage
performed significantly worse than comparison participants on both the verbal
and figural portions of the TTCT. These findings suggest that hippocampus plays
a role critical in creative thinking, adding to a growing body of work pointing
to the diverse ways the hallmark processing features of hippocampus serve a
variety of behaviors that require flexible cognition.
hippocampus; creativity; representational flexibility; relational binding; amnesia
An interesting area with great potential for benefiting and enriching the lives and conditions of people and animals is opening to us in research, service and teaching. By working with colleagues in other disciplines, we can develop new and creative ways to realize the great promise inherent in people-animal interactions properly studied and utilized.
Veterinarians who understand that a strong human-companion animal bond can augment people's mental and physical states will help develop sound and effective companion animal programs for individuals who are lonely or handicapped and for persons in the school systems of the community, as well as its hospices, nursing and convalescent homes, prisons and other institutions. Children experiencing the deep satisfaction of interacting with animals while young will more likely become responsible pet owners and advocates as adults. The image of the profession is enhanced when children and adults see veterinarians as concerned teachers and compassionate health professionals.
We as professionals will be required not only to update our knowledge and skills, but to acquire new knowledge in fields of animal and human behavior, psychology and sociology. We are needed on interdisciplinary research teams to study human-animal interactions. We will also be asked to commit time and personal energies in community programs, sometimes with no remuneration. But if skilled health professionals like veterinarians do not take the lead in establishing sound, long-term companion animal programs in their own communities, everyone will suffer including the animals. How we, as individual professionals, respond will be an important reflection of our compassion and our humanity.
The relationship between intelligence and creativity has been subject to empirical research for decades. Nevertheless, there is yet no consensus on how these constructs are related. One of the most prominent notions concerning the interplay between intelligence and creativity is the threshold hypothesis, which assumes that above-average intelligence represents a necessary condition for high-level creativity. While earlier research mostly supported the threshold hypothesis, it has come under fire in recent investigations. The threshold hypothesis is commonly investigated by splitting a sample at a given threshold (e.g., at 120 IQ points) and estimating separate correlations for lower and upper IQ ranges. However, there is no compelling reason why the threshold should be fixed at an IQ of 120, and to date, no attempts have been made to detect the threshold empirically. Therefore, this study examined the relationship between intelligence and different indicators of creative potential and of creative achievement by means of segmented regression analysis in a sample of 297 participants. Segmented regression allows for the detection of a threshold in continuous data by means of iterative computational algorithms. We found thresholds only for measures of creative potential but not for creative achievement. For the former the thresholds varied as a function of criteria: When investigating a liberal criterion of ideational originality (i.e., two original ideas), a threshold was detected at around 100 IQ points. In contrast, a threshold of 120 IQ points emerged when the criterion was more demanding (i.e., many original ideas). Moreover, an IQ of around 85 IQ points was found to form the threshold for a purely quantitative measure of creative potential (i.e., ideational fluency). These results confirm the threshold hypothesis for qualitative indicators of creative potential and may explain some of the observed discrepancies in previous research. In addition, we obtained evidence that once the intelligence threshold is met, personality factors become more predictive for creativity. On the contrary, no threshold was found for creative achievement, i.e. creative achievement benefits from higher intelligence even at fairly high levels of intellectual ability.
•We investigate the threshold hypothesis on the relationship of intelligence and creativity.•Segmented regression analysis is used for empirical detection of the IQ breakpoint.•Threshold hypothesis is confirmed for different indicators of creative potential.•IQ thresholds are higher for more demanding measures of creative potential.•Intelligence reflects a necessary but not sufficient condition for high creative potential.
Threshold hypothesis; Intelligence; Creativity; Segmented regression; Breakpoint detection
Adherence to effective malaria medication is extremely important in the context of Cambodia’s elimination targets and drug resistance containment. Although the public sector health facilities are accessible to the local ethnic minorities of Ratanakiri province (Northeast Cambodia), their illness itineraries often lead them to private pharmacies selling “cocktails” and artemether injections, or to local diviners prescribing animal sacrifices to appease the spirits.
The research design consisted of a mixed methods study, combining qualitative (in-depth interviews and participant observation) and quantitative methods (household and cross-sectional survey).
Three broad options for malaria treatment were identified: i) the public sector; ii) the private sector; iii) traditional treatment based on divination and ceremonial sacrifice. Treatment choice was influenced by the availability of treatment and provider, perceived side effects and efficacy of treatments, perceived etiology of symptoms, and patient-health provider encounters. Moreover, treatment paths proved to be highly flexible, changing mostly in relation to the perceived efficacy of a chosen treatment.
Despite good availability of anti-malarial treatment in the public health sector, attendance remained low due to both structural and human behavioral factors. The common use and under-dosage of anti-malaria monotherapy in the private sector (single-dose injections, single-day drug cocktails) represents a threat not only for individual case management, but also for the regional plan of drug resistance containment and malaria elimination.
Children consume restaurant-prepared foods at high rates, suggesting that interventions and policies targeting consumption of these foods have the potential to improve diet quality and attenuate excess energy intake. One approach to encouraging healthier dietary intake in restaurants is to offer fruits and vegetables (FV) as side dishes, as opposed to traditional, energy-dense accompaniments like French fries. The aims of the current study were to examine: children's views about healthier side dishes at restaurants; current side dish offerings on children's menus at leading restaurants; and potential energy reductions when substituting FV side dishes in place of French fries.
To investigate children’s attitudes, a survey was administered to a nationally representative sample of U.S. 8- to 18-year-olds (n = 1178). To examine current side dish offerings, children's menus from leading quick service (QSR; n = 10) and full service restaurant chains (FSR; n = 10) were analyzed. Energy reductions that could result from substituting commonly-offered FV side dishes for French fries were estimated using nutrition information corresponding to the children's menu items.
Two-thirds of children reported that they would not feel negatively about receiving FV sides instead of French fries with kids' meals. Liking/taste was the most common reason that children gave to explain their attitudes about FV side dishes. Nearly all restaurants offered at least 1 FV side dish option, but at most restaurants (60% of QSR; 70% of FSR), FV sides were never served by default. Substituting FV side dishes for French fries yielded an average estimated energy reduction of at least 170 calories.
Results highlight some healthy trends in the restaurant context, including the majority of children reporting non-negative attitudes about FV side dishes and the consistent availability of FV side dish options at leading QSR and FSR. Yet the minority of restaurants offer these FV sides by default. Promoting creative, appealing FV side dishes can result in healthier, less energy-dense meals for children. Substituting or displacing energy-dense default side dishes with such FV dishes show promise as part of continued, comprehensive efforts to increase the healthfulness of meals consumed by children in restaurant settings.
Restaurants; Children; Food away from home; Fruit; Vegetables; Side dishes; Defaults; Healthy eating; Childhood obesity
The author presents in this article many evidence to prove that the cross is a symbol of soul.
Human genetic variations primarily result from single nucleotide polymorphisms (SNPs) that occur approximately every 1000 bases in the overall human population. The non-synonymous SNPs (nsSNPs) that lead to amino acid changes in the protein product may account for nearly half of the known genetic variations linked to inherited human diseases. One of the key problems of medical genetics today is to identify nsSNPs that underlie disease-related phenotypes in humans. As such, the development of computational tools that can identify such nsSNPs would enhance our understanding of genetic diseases and help predict the disease.
We propose a method, named Parepro (Predicting the amino acid replacement probability), to identify nsSNPs having either deleterious or neutral effects on the resulting protein function. Two independent datasets, HumVar and NewHumVar, taken from the PhD-SNP server, were applied to train the model and test the robustness of Parepro. Using a 20-fold cross validation test on the HumVar dataset, Parepro achieved a Matthews correlation coefficient (MCC) of 50% and an overall accuracy (Q2) of 76%, both of which were higher than those predicted by the methods, such as PolyPhen, SIFT, and HydridMeth. Further analysis on an additional dataset (NewHumVar) using Parepro yielded similar results.
The performance of Parepro indicates that it is a powerful tool for predicting the effect of nsSNPs on protein function and would be useful for large-scale analysis of genomic nsSNP data.
Whether the integration of genetic/omic technologies in sports contexts will facilitate player success, promote player safety, or spur genetic discrimination depends largely upon the game rules established by those currently designing genomic sports medicine programs. The integration has already begun, but there is not yet a playbook for best practices. Thus far discussions have focused largely on whether the integration would occur and how to prevent the integration from occurring, rather than how it could occur in such a way that maximizes benefits, minimizes risks, and avoids the exacerbation of racial disparities. Previous empirical research has identified members of the personal genomics industry offering sports-related DNA tests, and previous legal research has explored the impact of collective bargaining in professional sports as it relates to the employment protections of the Genetic Information Nondiscrimination Act (GINA). Building upon that research and upon participant observations with specific sports-related DNA tests purchased from four direct-to-consumer companies in 2011 and broader personal genomics (PGx) services, this anthropological, legal, and ethical (ALE) discussion highlights fundamental issues that must be addressed by those developing personal genomic sports medicine programs, either independently or through collaborations with commercial providers. For example, the vulnerability of student-athletes creates a number of issues that require careful, deliberate consideration. More broadly, however, this ALE discussion highlights potential sports-related implications (that ultimately might mitigate or, conversely, exacerbate racial disparities among athletes) of whole exome/genome sequencing conducted by biomedical researchers and clinicians for non-sports purposes. For example, the possibility that exome/genome sequencing of individuals who are considered to be non-patients, asymptomatic, normal, etc. will reveal the presence of variants of unknown significance in any one of the genes associated with hypertrophic cardiomyopathy (HCM), long QT syndrome (LQTS), Marfan’s syndrome, and other conditions is not inconsequential, and how this information is reported, interpreted, and used may ultimately prevent the individual from participation in competitive sports. Due to the distribution of genetic diversity that reflects our evolutionary and demographic history (including the discernible effects of restricted gene flow and genetic drift associated with cultural constructs of race) and in recognition of previous policies for “leveling” the playing field in competitive sports based on “natural” athletic abilities, preliminary recommendations are provided to discourage genetic segregation of sports and to develop best practice guidelines for genomic sports medicine programs that will facilitate player success, promote player safety, and avoid genetic discrimination within and beyond the program.
Legal issues; Personal genomics; Athletes; Sports; GINA; ELSI; Discrimination; Privacy; Sports medicine; Genetic screening
To evaluate whether the evidence-based Body & Soul program, when disseminated and implemented without researcher or agency involvement and support, would achieve similar results to earlier efficacy and effectiveness trials.
Prospective group randomized trial.
Churches with predominantly African American membership.
A total of 1033 members from the fifteen churches completed baseline surveys. Of these, 562 (54.4%) completed the follow-up survey six months later.
Church-based nutrition program for African Americans that included pastoral involvement, educational activities, church environmental changes, and peer counseling.
Main Outcome Measure
Daily fruit and vegetable (FV) intake was assessed at pre- and post-test.
Mixed-effects linear models.
At posttest, there was no statistically significant difference in daily servings of FV between the early intervention group participants compared to control group participants (4.7 vs, 4.4, P=0.38). Process evaluation suggested that added resources such as technical assistance could improve program implementation.
Conclusions and Implications
The disseminated program may not produce improvements in FV intake equal to those in the earlier efficacy and effectiveness trials, primarily due to lack of program implementation. Program dissemination may not achieve public health impact unless support systems are strengthened for adequate implementation at the church level.
diet; health behavior; health promotion; program evaluation; African Americans
We report on an in-depth qualitative study of 28 active and former substance addicted women of low or marginal income on the core components of a harm reduction-based addiction recovery program. These women volunteered to be interviewed about their perceptions of their therapeutic needs in their transition from substance addiction to recovery.
Data were gathered about women’s experiences and essential needs in addiction recovery, what helped and what hindered their past efforts in recovery, and their views of what would constitute an effective woman-centred recovery program. The research was based upon the experience and knowledge of the women in interaction with their communities and with recovery programs. The study was informed by harm reduction practice principles that emphasize the importance of individual experience in knowledge construction, reduction of harm, low threshold access, and the development of a hierarchy of needs in regard to addiction recovery.
Three core needs were identified by study participants: normalization and structure, biopsychosocial-spiritual safety, and social connection. What hindered recovery efforts as identified by participants was an inner urban location, prescriptive recovery, invidious treatment, lack of safety, distress-derived distraction, problem-focused treatment, coercive elements of mutual support groups, and social marginalization. What helped included connection in counselling and therapy, multidisciplinary service provision, spirituality focus, opportunities for learning and work, and a safe and flexible structure. Core components of an effective recovery program identified by women themselves stand in contrast to the views of service providers and policymakers, particularly in regard to the need for a rural location for residential programs, low threshold access, multidisciplinary service provision of conventional and complementary modalities and therapies for integrated healing, long-term multi-phase recovery, and variety and choice of programming.
A key barrier to the addiction recovery of women is the present framework of addiction treatment, as well as current drug laws, policies and service delivery systems. The expectation of women is that harm reduction-based recovery services will facilitate safe, supportive transitioning from the point of the decision to access services, through independent living with community integration.
To examine the relationship between cardiac self-efficacy and health status, including symptom burden, physical limitation, quality of life, and overall health among outpatients with stable coronary heart disease (CHD). We hypothesized that lower self-efficacy would predict worse health status, independent of CHD severity and depression.
We performed a cross-sectional study of 1024 outpatients with CHD, who were recruited between 2000 and 2002 for the Heart and Soul Study. We administered a validated measure of cardiac self-efficacy, assessed cardiac function using exercise treadmill testing with stress echocardiography, and measured depressive symptoms using the Patient Health Questionnaire. Health status outcomes (symptom burden, physical limitation, and quality of life) were assessed using the Seattle Angina Questionnaire, and overall health was measured as fair or poor (versus good, very good, or excellent).
After adjustment for CHD severity and depressive symptoms, each standard deviation (4.5-point) decrease in self-efficacy score was independently associated with greater symptom burden (adjusted odds ratio (OR) = 2.1, p = .001), greater physical limitation (OR = 1.8, p < .0001), worse quality of life (OR = 1.6, p < .0001), and worse overall health (OR = 1.9, p < .0001). Depressive symptoms and poor treadmill exercise capacity were also associated with poor health status, but left ventricular ejection fraction and ischemia were not.
Among patients with CHD, low cardiac self-efficacy is associated with poor health status, independent of CHD severity and depressive symptoms. Further study should examine if self-efficacy constitutes a useful target for cardiovascular disease management interventions.
self-efficacy; health status; heart disease; epidemiology
Cystatin C, an alternative serum measure of kidney function, is a stronger predictor of cardiovascular events than creatinine or estimated glomerular filtration rate (eGFR). We hypothesized that serum cystatin C concentration would have a stronger more linear association with cardiovascular functional status than creatinine-based measures in outpatients with established coronary heart disease (CHD).
We measured serum cystatin C, serum creatinine, and eGFR in 906 outpatients with established CHD. We examined the association of these 3 measures of kidney function with treadmill exercise capacity (metabolic equivalent tasks achieved) and heart rate recovery (HRR) between peak and 1 minute after exercise by using linear and logistic regression.
Higher cystatin C concentrations were associated linearly with worse treadmill exercise capacity and HRR. The proportion of participants with poor exercise capacity (metabolic equivalent tasks achieved < 5) was 45% (99 of 222 participants) among those with cystatin C levels in the highest quartile (>1.30 mg/L) compared with 12% (29 of 241 participants) among those with cystatin C levels in the lowest quartile (<0.92 mg/L; adjusted odds ratio, 3.2; 95% confidence interval, 1.6 to 6.5; P = 0.001). The proportion of participants with poor HRR (<16 beats/min) was 42% (92 of 214 participants) among those with cystatin C levels in the highest quartile compared with 16% (37 of 238 participants) among those with cystatin C levels in the lowest quartile (adjusted odds ratio, 2.2; 95% confidence interval, 1.2 to 4.0; P = 0.01). The lowest quartile of eGFR (<61.8 mL/min [<1.03 mL/s]) was associated with decreased exercise capacity and prolonged HRR, but no difference was observed across the upper 3 quartiles of eGFR.
In patients with established CHD, cystatin C concentrations are associated linearly with worse exercise capacity and HRR. Cystatin C detects an association of impaired kidney function with decreased HRR and exercise capacity that is not fully captured using creatinine-based measurements.
Coronary artery disease; cystatin C; creatinine; renal function; exercise capacity; heart rate recovery
Apoptosis is a fundamental biologic process by which metazoan cells orchestrate their own self-demise. Genetic analyses of the nematode C elegans identified three core components of the suicide apparatus which include CED-3, CED-4, and CED-9. An analogous set of core constituents exists in mammalian cells and includes caspase-9, Apaf-1, and bcl-2/xl, respectively. CED-3 and CED-4, along with their mammalian counterparts, function to kill cells, whereas CED-9 and its mammalian equivalents protect cells from death. These central components biochemically intermingle in a ternary complex recently dubbed the “apoptosome.” The C elegans protein EGL-1 and its mammalian counterparts, pro-apoptotic members of the bcl-2 family, induce cell death by disrupting apoptosome interactions. Thus, EGL-1 may represent a primordial signal integrator for the apoptosome. Various biochemical processes including oligomerization, adenosine triphosphate ATP/dATP binding, and cytochrome c interaction play a role in regulating the ternary death complex. Recent studies suggest that cell death receptors, such as CD95, may amplify their suicide signal by activating the apoptosome. These mutual associations by core components of the suicide apparatus provide a molecular framework in which diverse death signals likely interface. Understanding the apoptosome and its cellular connections will facilitate the design of novel therapeutic strategies for cancer and other disease states in which apoptosis plays a pivotal role.
apoptosis; apoptosome; cell death; death receptor
Fetuin-A is a multifunctional hepatic secretory protein that inhibits dystrophic vascular and valvular calcification. Lower serum fetuin-A concentrations are associated with valvular calcification in persons with end-stage renal disease. Whether fetuin-A is associated with valvular calcification in other patient populations is unknown.
Methods and Results
We evaluated the associations among serum fetuin-A concentrations, mitral annular calcification, and aortic stenosis in 970 ambulatory persons with coronary heart disease and without severe kidney disease. The presence or absence of mitral annular calcification and aortic stenosis was determined by transthoracic echocardiography. The subjects’ mean age was 66 years; 81% were men; 189 (20%) had mitral annular calcification; and 79 (8%) had aortic stenosis. Participants were categorized by tertiles of fetuin-A concentrations. Those within the highest fetuin-A tertile had significantly lower odds of mitral annular calcification compared with the lowest tertile (adjusted odds ratio, 0.47; 95% confidence interval, 0.29 to 0.77; P=0.002); this association was similar regardless of diabetes status (P for interaction=0.34). In contrast, the association of fetuin-A with aortic stenosis was modified by the presence or absence of diabetes mellitus (P for interaction=0.03). Among participants without diabetes, the highest fetuin-A tertile had a significantly lower odds of aortic stenosis compared with the lowest tertile (adjusted odds ratio, 0.37; 95% confidence interval, 0.15 to 0.92; P=0.03), whereas among participants with diabetes, no statistically significant association was observed between fetuin-A and aortic stenosis (adjusted odds ratio, 1.49; 95% confidence interval, 0.48 to 4.63; P=0.49).
Among persons with coronary heart disease, we observed an inverse association of fetuin-A and mitral annular calcification. An inverse association also was observed between fetuin-A and aortic stenosis among participants without diabetes mellitus. Fetuin-A may represent an important inhibitor of dystrophic calcification in persons with coronary heart disease.
alpha2HS-glycoprotein; calcium; diabetes mellitus; fetuin-A, human; valves