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1.  The Soul and the Body in the Philosophy of the Rambam 
Among the wide-spectrum contribution of the Rambam – the Maimonides – in philosophy to the word and to Judaism are his ideas on the body and on the soul and on the relations between them. His major approaches in these subjects are the following: 1) The body is the home of the soul, and the soul guides the body. That means the body and the soul are one unit. 2) The soul has five virtual parts. Each part is responsible for another activity in the human being. 3) Except for the treatment of diseases of the body and the soul with drugs, foods, physical exercise, etc., the Rambam believes that maintaining the health – of the body and of the soul – lies first of all, and probably exclusively, in observing the commandments and improving one’s ways, morals and conduct up to their highest levels, toward all of the world’s creatures. 4) The Rambam is of the opinion that one needs to persist in learning the Torah. One should worship God with awe and love and observe good values and virtues. All of these build the frameworks that maintain mental health and strengthen man’s abilities to develop skills for maintaining bodily health. This is so because body and soul are one – which is the basis of the Rambam’s philosophy of health and medicine.
PMCID: PMC3678934  PMID: 23908798
Maimonides; Rambam; soul; body; soul-body
Ancient Science of Life  1989;8(3-4):191-195.
Alchemy as art tries to imitate creation such as spontaneous generation. The magic wands of creation, of Chinese origin, would be a compass and a triangular carpenter's square. Creation is represented by the dual-natured soul, comprising of the spirit (Ruh) and “the” soul (Nafs). The ultimate source is creative energy which emanates form the Divine word of command. Creative energy, in its non-manifest form, would be ultrasonic energy, which can be represented by a humming sourd. This would be sympolized by the humming sound. This would be symbolized by the humming sound of bees represent creative energy and in fig 3 the fiddle, as direct producers of a humming sound.
PMCID: PMC3336720  PMID: 22557649
3.  Understanding Brain, Mind and Soul: Contributions from Neurology and Neurosurgery 
Mens Sana Monographs  2011;9(1):129-149.
Treatment of diseases of the brain by drugs or surgery necessitates an understanding of its structure and functions. The philosophical neurosurgeon soon encounters difficulties when localising the abstract concepts of mind and soul within the tangible 1300-gram organ containing 100 billion neurones. Hippocrates had focused attention on the brain as the seat of the mind. The tabula rasa postulated by Aristotle cannot be localised to a particular part of the brain with the confidence that we can localise spoken speech to Broca’s area or the movement of limbs to the contralateral motor cortex. Galen’s localisation of imagination, reasoning, judgement and memory in the cerebral ventricles collapsed once it was evident that the functional units–neurones–lay in the parenchyma of the brain. Experiences gained from accidental injuries (Phineas Gage) or temporal lobe resection (William Beecher Scoville); studies on how we see and hear and more recent data from functional magnetic resonance studies have made us aware of the extensive network of neurones in the cerebral hemispheres that subserve the functions of the mind. The soul or atman, credited with the ability to enliven the body, was located by ancient anatomists and philosophers in the lungs or heart, in the pineal gland (Descartes), and generally in the brain. When the deeper parts of the brain came within the reach of neurosurgeons, the brainstem proved exceptionally delicate and vulnerable. The concept of brain death after irreversible damage to it has made all of us aware of ‘the cocktail of brain soup and spark’ in the brainstem so necessary for life. If there be a soul in each of us, surely, it is enshrined here.
PMCID: PMC3115284  PMID: 21694966
Brain; Brainstem; Mind; Soul; Neurology; Neurosurgery; Philosophy
4.  The soul and the pneuma in the function of the nervous system after Galen. 
Galen's teaching on anatomy and physiology was generally accepted in the Middle Ages and this applies to the part he thought was played by the pneuma in the functions of the body. In this essay I have outlined the advances made after Galen in the study of the nervous system leading eventually to a time when the soul and the pneuma were no longer thought necessary for the proper functioning of the brain and nerves.
PMCID: PMC1294649  PMID: 8046725
Ancient Science of Life  1988;8(2):113-116.
In this paper the author discusses five souls viz, prana, Apana, Udana, Samana and vyana of Indian physiology. Also aims to show that the last named two souls were unknown to Galen.
PMCID: PMC3331365  PMID: 22557641
Ancient Science of Life  1988;8(1):44-48.
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.
PMCID: PMC3331348  PMID: 22557629
Ancient Science of Life  1991;10(3):191-193.
The author presents in this article many evidence to prove that the cross is a symbol of soul.
PMCID: PMC3331288  PMID: 22556532
8.  Lifetime exposure to traumatic psychological stress is associated with elevated inflammation in the heart and soul study 
Brain, Behavior, and Immunity  2012;26(4):642-649.
Exposure to traumatic psychological stress increases risk for disease events and mortality in patients with cardiovascular disease (CVD). While the biological mechanisms of these effects are not known, inflammation may play a key role as it is both elevated by psychological stress and involved in the development and progression of CVD. In a prospective study of patients with stable CVD (n = 979), we examined if higher lifetime trauma exposure was associated with elevated levels of inflammation at baseline and at five-year follow-up, and with greater increases in inflammation over time. Inflammation was indexed by a composite score incorporating the inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and resistin. In follow-up analyses, we adjusted for sociodemographic factors, psychiatric disorders and health behaviors that were significantly associated with trauma exposure. Higher trauma exposure was associated with elevated inflammation at baseline (β = .09, p = .01) and at five-year follow-up (β = .09, p = .03). While levels of inflammation increased from baseline to follow-up in the sample, there was no significant association between trauma exposure and rate of change in inflammation. Findings were robust to adjustments for sociodemographic factors and psychiatric disorders, but health behaviors appeared to contribute to the association between trauma and inflammation at follow-up. This is the first large-scale demonstration of an association between lifetime trauma exposure and inflammation. High lifetime exposure to traumatic stress may contribute to an accelerated rate of CVD progression through elevated inflammation.
PMCID: PMC3322304  PMID: 22366689
Aging; cardiovascular disease; C-reactive protein; immune system; inflammation; interleukin-6; psychological stress; resistin; traumatic psychological stress; tumor necrosis factor-α
9.  Preliminary structural characterization of human SOUL, a haem-binding protein 
This manuscript describes the overexpression, purification and crystallization of human SOUL protein (hSOUL). hSOUL is a 23 kDa haem-binding protein that was first identified as the PP23 protein isolated from human full-term placenta.
Human SOUL (hSOUL) is a 23 kDa haem-binding protein that was first identified as the PP23 protein isolated from human full-term placentas. Here, the overexpression, purification and crystallization of hSOUL are reported. The crystals belonged to space group P6422, with unit-cell parameters a = b = 145, c = 60 Å and one protein molecule in the asymmetric unit. X-ray diffraction data were collected to 3.5 Å resolution at the ESRF. A preliminary model of the three-dimensional structure of hSOUL was obtained by molecular replacement using the structures of murine p22HBP (PDB codes 2gov and 2hva), obtained by solution NMR, as search models.
PMCID: PMC2705645  PMID: 19574650
haem-binding proteins; SOUL
10.  Structural changes in the BH3 domain of SOUL protein upon interaction with the anti-apoptotic protein Bcl-xL 
Biochemical Journal  2011;438(Pt 2):291-301.
The SOUL protein is known to induce apoptosis by provoking the mitochondrial permeability transition, and a sequence homologous with the BH3 (Bcl-2 homology 3) domains has recently been identified in the protein, thus making it a potential new member of the BH3-only protein family. In the present study, we provide NMR, SPR (surface plasmon resonance) and crystallographic evidence that a peptide spanning residues 147–172 in SOUL interacts with the anti-apoptotic protein Bcl-xL. We have crystallized SOUL alone and the complex of its BH3 domain peptide with Bcl-xL, and solved their three-dimensional structures. The SOUL monomer is a single domain organized as a distorted β-barrel with eight anti-parallel strands and two α-helices. The BH3 domain extends across 15 residues at the end of the second helix and eight amino acids in the chain following it. There are important structural differences in the BH3 domain in the intact SOUL molecule and the same sequence bound to Bcl-xL.
PMCID: PMC3174058  PMID: 21639858
apoptosis; Bcl-xL; Bcl-2 homology 3 domain (BH3 domain); crystal structure; NMR; SOUL; surface plasmon resonance; BH, Bcl-2 homology; HEBP, haem-binding protein; HSQC, heteronuclear single-quantum coherence; MPT, mitochondrial permeability transition; rmsd, root mean square deviation; RZPD, Deutsches Ressouroenzentrum für Genomforschung; SPR, surface plasmon resonance
Ancient Science of Life  1989;9(1):25.
The author traces in this paper the clue of the Tridosha Doctrine consisting of Air, water and heat. Breath contains all the three. Probably the Tridosha doctrine arose while considering breath as soul.
PMCID: PMC3331300  PMID: 22557670
12.  A home for body and soul: Substance using women in recovery 
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.
PMCID: PMC3878194  PMID: 24359089
13.  Process evaluation of Healthy Bodies, Healthy Souls: a church-based health intervention program in Baltimore City 
Health Education Research  2013;28(3):392-404.
Soaring obesity rates in the United States demand comprehensive health intervention strategies that simultaneously address dietary patterns, physical activity, psychosocial factors and the food environment. Healthy Bodies, Healthy Souls (HBHS) is a church-based, community-participatory, cluster-randomized health intervention trial conducted in Baltimore City to reduce diabetes risk among urban African Americans by promoting healthy dietary intake, increased physical activity and improvement to the church food environment. HBHS was organized into five 3–8-week phases: Healthy Beverages, Healthy Desserts, Healthy Cooking, Healthy Snacking and Eating Out and Physical Activity. A three-part process evaluation was adopted to evaluate implementation success: an in-church instrument to assess the reach, dose delivered and fidelity of interactive sessions; a post-intervention exposure survey to assess individual-level dose received in a sample of congregants and an evaluation form to assess the church food environment. Print materials were implemented with moderate to high fidelity and high dose. Program reach was low, which may reflect inaccuracies in church attendance rather than study implementation issues. Intervention components with the greatest dose received were giveaways (42.0–61.7%), followed by taste tests (48.7–53.7%) and posters (34.3–65.0%). The dose received of general program information was moderate to high. The results indicate successful implementation of the HBHS program.
PMCID: PMC3649211  PMID: 23525780
14.  The Apoptosome: Heart and Soul of the Cell Death Machine 
Neoplasia (New York, N.Y.)  1999;1(1):5-15.
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.
PMCID: PMC1716059  PMID: 10935465
apoptosis; apoptosome; cell death; death receptor
15.  Telomere Length Trajectory and Its Determinants in Persons with Coronary Artery Disease: Longitudinal Findings from the Heart and Soul Study 
PLoS ONE  2010;5(1):e8612.
Leukocyte telomere length, an emerging marker of biological age, has been shown to predict cardiovascular morbidity and mortality. However, the natural history of telomere length in patients with coronary artery disease has not been studied. We sought to investigate the longitudinal trajectory of telomere length, and to identify the independent predictors of telomere shortening, in persons with coronary artery disease.
Methodology/Principal Findings
In a prospective cohort study of 608 individuals with stable coronary artery disease, we measured leukocyte telomere length at baseline, and again after five years of follow-up. We used multivariable linear and logistic regression models to identify the independent predictors of leukocyte telomere trajectory. Baseline and follow-up telomere lengths were normally distributed. Mean telomere length decreased by 42 base pairs per year (p<0.001). Three distinct telomere trajectories were observed: shortening in 45%, maintenance in 32%, and lengthening in 23% of participants. The most powerful predictor of telomere shortening was baseline telomere length (OR per SD increase = 7.6; 95% CI 5.5, 10.6). Other independent predictors of telomere shortening were age (OR per 10 years = 1.6; 95% CI 1.3, 2.1), male sex (OR = 2.4; 95% CI 1.3, 4.7), and waist-to-hip ratio (OR per 0.1 increase = 1.4; 95% CI 1.0, 2.0).
Leukocyte telomere length may increase as well as decrease in persons with coronary artery disease. Telomere length trajectory is powerfully influenced by baseline telomere length, possibly suggesting negative feedback regulation. Age, male sex, and abdominal obesity independently predict telomere shortening. The mechanisms and reversibility of telomeric aging in cardiovascular disease deserve further study.
PMCID: PMC2797633  PMID: 20072607
16.  Are Eyes Windows to a Deceiver's Soul? Children's Use of Another's Eye Gaze Cues in a Deceptive Situation 
Developmental psychology  2004;40(6):1093-1104.
Three experiments examined 3- to 5-year-olds' use of eye gaze cues to infer truth in a deceptive situation. Children watched a video of an actor who hid a toy in 1 of 3 cups. In Experiments 1 and 2, the actor claimed ignorance about the toy's location but looked toward 1 of the cups, without (Experiment 1) and with (Experiment 2) head movement. In Experiment 3, the actor provided contradictory verbal and eye gaze clues about the location of the toy. Four- and 5-year-olds correctly used the actor's gaze cues to locate the toy, whereas 3-year-olds failed to do so. Results suggest that by 4 years of age, children begin to understand that eye gaze cues displayed by a deceiver can be informative about the true state of affairs.
PMCID: PMC2567061  PMID: 15535759
17.  Usefulness of Diastolic Dominant Pulmonary Vein Flow to Predict Hospitalization for Heart Failure and Mortality in Ambulatory Patients with Coronary Heart Disease (From the Heart and Soul Study) 
The American journal of cardiology  2008;103(4):482-485.
Diastolic dysfunction is usually identified by the combination of characteristic mitral and pulmonary vein flow patterns. However, obtaining a complete set of echocardiographic parameters can be technically difficult and data may conflict. We hypothesized that, as a stand alone variable, diastolic (ventricular diastole) dominant pulmonary vein flow predicts heart failure (HF) hospitalizations and cardiovascular (CV) death. Standard transthoracic echocardiograms were performed in 906 participants from the Heart and Soul Study, a prospective study of the effects of depression on coronary heart disease. Pulmonary vein flow pattern was determined by the dominant velocity time integral. Cardiac events were determined by two independent adjudicators and Cox proportional hazards models were used. Systolic dominant pulmonary vein flow was present in 89% of the participants, and diastolic dominant in the remaining 11%. During an average 4.1 years of follow-up, participants with diastolic dominant pulmonary vein flow had a 25% rate of HF hospitalization and 9% rate of CV death. After multivariate adjustment including left ventricular ejection fraction, diastolic pulmonary vein flow was associated with a three-fold risk for HF hospitalization (p=0.001) and a two-fold risk for HF hospitalization or death (p=0.004). In conclusion, diastolic dominant pulmonary vein flow pattern is a stand alone predictor of adverse cardiac events and its presence is associated with significantly higher rates of HF hospitalizations and CV death.
PMCID: PMC2680227  PMID: 19195506
pulmonary vein flow; echocardiography; heart failure; prognosis
18.  The Soul’s Wisdom: Stories of Living and Dying 
Current Oncology  2008;15(Suppl 2):s107.es48-s107.es52.
Cancer can lead to spiritual transformation, which can be seen as a form of alchemy. During this process, patients, family members, and even professional caregivers can find themselves having spiritual experiences that go beyond any they had previously encountered. This paper provides qualitative descriptions of the “Field” or “Soul Wisdom” experienced by patients and caregivers.
PMCID: PMC2528551  PMID: 18769614
19.  Relation of Beta Blocker Use With Frequency of Hospitalization for Heart Failure in Patients With Left Ventricular Diastolic Dysfunction (From the Heart and Soul Study) 
The American journal of cardiology  2010;105(2):223-228.
Heart failure (HF) is a common public health problem, and many new cases are now recognized to occur in patients with preserved left ventricular (LV) ejection fraction. Beta blockers improve outcomes in patients with known LV systolic dysfunction, but whether beta blockers provide similar protection in patients with LV diastolic dysfunction is unclear. We studied the association between the use of beta blockers and subsequent hospitalization for HF in patients with diastolic dysfunction and stable coronary heart disease (CHD). We evaluated medication use and performed echocardiography at baseline in a prospective cohort of 911 outpatients with known CHD from the Heart and Soul Study. Hospitalizations for HF were assessed by blinded review of medical records during an average of 5.2 years of follow-up. Of the 911 participants, 118 (13%) had diastolic dysfunction, of which 2 were lost to follow-up. Among the 116 remaining patients, 25% (19/77) of those using beta blockers were hospitalized for HF compared with 41% (16/39) of those not using beta blockers [age-adjusted hazard ratio (HR) 0.51, 95% Confidence Interval 0.26-1.00; p = 0.05]. This association remained after further adjustment for sex, smoking, history of myocardial infarction, diabetes, and creatinine (HR 0.46, 0.23-0.93; p = 0.03). Results were similar after excluding 31 participants with a history of self-reported HF (HR 0.33, 0.13-0.86; p = 0.02) and 24 participants with concurrent systolic dysfunction (HR 0.36, 0.14-0.89; p = 0.03). In conclusion, the use of beta blockers is associated with a decreased risk of hospitalization for HF in patients with diastolic dysfunction and stable CHD.
PMCID: PMC2827308  PMID: 20102923
Coronary disease; diastole; echocardiography; heart failure; adrenergic beta antagonists
20.  Fibroblast growth factor-23 and early decrements in kidney function: the Heart and Soul Study 
Background. Fibroblast growth factor-23 (FGF-23) is associated with mortality in dialysis patients, and concentrations are elevated in moderate chronic kidney disease (CKD). The threshold of CKD or albuminuria at which FGF-23 begins to change is unknown.
Methods. In 792 outpatients with stable cardiovascular disease (CVD) and normal kidney function to moderate CKD, we evaluate the associations of estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) with plasma FGF-23 concentrations.
Results. Compared to participants with eGFR ≥90 ml/min/1.73m2, mean FGF-23 concentrations were 7.8 RU/ml higher (4.3–11.5, P = 0.01) in those with eGFR 60–89 ml/min/1.73m2 in models adjusted for age, sex, race, ACR, blood pressure, diabetes and body mass index. More advanced decrements in eGFR were associated with much higher FGF-23 concentrations. In spline analysis, the slope of change in FGF-23 concentration was evident at eGFR <90 ml/min/1.73m2. Compared to participants with ACR <30 mg/g, mean FGF-23 concentrations were 18.4 RU/ml higher (9.3–29.2, P < 0.001) in those with ACR 30–299 mg/g in models adjusted for identical covariates plus eGFR and much higher in individuals with ACR ≥300 mg/g. Spline analysis demonstrated a linear relationship of ACR with FGF-23, independent of eGFR, even among persons with ACR <30 mg/g.
Conclusion. Modest decrements in eGFR or elevations in albuminuria are each independently associated with higher FGF-23 concentrations in outpatients with stable CVD.
PMCID: PMC2902926  PMID: 20037168
albuminuria; chronic; fibroblast growth factor-23; kidney disease; osteodystrophy
21.  Urinary Creatinine Excretion Rate and Mortality in Persons with Coronary Artery Disease: The Heart and Soul Study 
Circulation  2010;121(11):1295-1303.
In persons with coronary artery disease (CAD), low body mass index is associated with greater mortality, however it is uncertain if low muscle mass is a risk factor for mortality in this setting.
Methods and Results
903 individuals with CAD provided 24-hour urine collections. We measured urine creatinine and volume, and calculated creatinine excretion rate (CER), a marker of muscle mass. Cox proportional hazards models evaluated the association of CER with mortality risk during follow-up. Two-hundred thirty-two participants (26%) died over a median follow-up of 6.0 years. Compared to the highest sex-specific CER tertile, the lowest tertile (< 1,068 mg/day in men, < 766 mg/day in women) was associated with > 2-fold risk of mortality (hazard ratio [HR] 2.30; 95% confidence interval [CI] 1.51–3.51) in models adjusted for age, sex, race, cystatin C-based eGFR, body mass index, traditional CVD risk factors, and C-reactive protein levels. The association was essentially unaltered with further adjustment for physical fitness, left ventricular (LV) mass, LV ejection fraction, or fasting insulin and glucose levels.
Lower CER is strongly associated with mortality in outpatients with CAD, independent of conventional measures of body composition, kidney function, and traditional CAD risk factors. Future studies should determine whether low CER may be a modifiable risk factor for mortality among persons with CAD, potentially through resistive exercise training or nutrition interventions.
PMCID: PMC2844485  PMID: 20212276
Cardiovascular disease; mortality; lean mass; muscle mass; creatinine
22.  Prognostic value of electrocardiographic detection of unrecognized myocardial infarction in persons with stable coronary artery disease: data from the Heart and Soul Study 
Clinical Research in Cardiology  2010;100(4):359-366.
Unrecognized myocardial infarction (MI) carries a poor prognosis in the general population, but its prognostic value is less clear in high-risk patients. We sought to determine whether Q waves on electrocardiogram (ECG), suggestive of unrecognized MI, predict cardiovascular events in patients with stable coronary artery disease (CAD), but without a prior history of MI. We studied 462 patients enrolled in the Heart and Soul Study with stable CAD but without a prior history of MI. All patients had baseline ECGs. The baseline prevalence of unrecognized myocardial infarction was 36%. After a mean of 6.3 years of follow-up, there were a total of 141 cardiovascular events. The presence of Q waves in any ECG lead territory predicted cardiovascular events before (unadjusted HR 1.41, 95% CI 1.01–1.97) and after adjustment for demographics, medical history, diastolic function, and ejection fraction (HR 1.55, 95% CI 1.06–2.26). This association was partly attenuated after adjustment for the presence of inducible ischemia at baseline (HR 1.43, 95% CI 0.96–2.12). When specific territories were analyzed separately, Q waves in anterior leads were predictive of cardiovascular events in both unadjusted and adjusted models (adjusted HR 1.85, 95% CI 1.14–3.00), and this association was partly attenuated after adjustment for inducible ischemia. In conclusion, in patients with CAD but no history of prior MI, the presence of any Q waves or anterior Q waves alone is independently predictive of adverse cardiovascular events.
PMCID: PMC3062762  PMID: 21103882
Q wave; Unrecognized myocardial infarction; Electrocardiogram; Coronary artery disease
23.  The Associations of Fibroblast Growth Factor 23 and Uncarboxylated Matrix Gla Protein With Mortality in Coronary Artery Disease: The Heart and Soul Study 
Annals of internal medicine  2010;152(10):640-648.
Fibroblast growth factor 23 (FGF23), uncarboxylated matrix Gla protein (ucMGP), and fetuin-A are regulators of mineral metabolism and inhibitors of vascular calcification. Whether circulating levels of each are associated with cardiovascular disease (CVD) events or mortality in populations without end-stage renal disease is unknown.
To evaluate the associations of FGF23, ucMGP, and fetuin-A with mortality and CVD events.
Observational study.
12 outpatient clinics in the San Francisco Bay area.
833 outpatients with stable coronary artery disease (CAD), recruited from 11 September 2000 to 20 December 2002.
Fibroblast growth factor 23, ucMGP, and fetuin-A concentrations were measured at baseline. Participants were followed until 1 December 2008 for mortality and CVD events.
During a median follow-up of 6.0 years, 220 participants died and 182 had CVD events. Compared with participants with FGF-23 levels in the lowest tertile, those in the highest tertile had 2-fold greater risk for mortality (hazard ratio [HR], 2.15 [95% CI, 1.43 to 3.24]) and CVD events (HR, 1.83 [CI, 1.15 to 2.91]) after adjustment for traditional CVD risk factors, C-reactive protein levels, and kidney function. The highest ucMGP tertile was associated with lower mortality risk (HR, 0.48 [CI, 0.31 to 0.75]) and showed a nonsignificant trend toward lower CVD event risk by tertile analysis (HR, 0.65 [CI, 0.40 to 1.05])—an association that was significant when modeled continuously (P = 0.029). No significant association of fetuin-A with mortality (HR, 0.84 [CI, 0.55 to 1.27]) or CVD events (HR, 0.99 [CI, 0.64 to 1.55]) was observed.
Participants had prevalent CAD.
In outpatients with stable CAD, higher FGF23 and lower ucMGP levels are independently associated with mortality and CVD events.
Primary Funding Source
American Heart Association.
PMCID: PMC3079370  PMID: 20479029
24.  The Association of Uncarboxylated Matrix Gla Protein with Mitral Annular Calcification Differs by Diabetes Status: The Heart and Soul Study 
Atherosclerosis  2009;210(1):320-325.
Mitral annular calcification (MAC) and aortic stenosis (AS) are associated with systemic calcification and cardiovascular disease (CVD) events. Matrix Gla protein (MGP) is an inhibitor of vascular calcification and lower levels of its precursor – uncarboxylated MGP (ucMGP) – are associated with vascular calcification in pilot studies.
Methods and Results
In this cross-sectional study of 839 outpatients with stable CVD, we measured serum ucMGP, and evaluated MAC and AS by echocardiography. The association of ucMGP with MAC differed by diabetes status (interaction P<0.001). Among participants without diabetes (n=615), higher ucMGP (per standard deviation [1,178 nM] increase) was associated with lower odds of MAC (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.55-0.97) in models adjusted for traditional CVD risk factors, C-reactive protein, and kidney function. Among persons with diabetes (n=221), higher ucMGP was associated with higher odds of MAC (OR 1.89; 95% CI 1.29-2.78). Results were qualitatively similar for the association of ucMGP with AS although not statistically significant.
Among outpatients with stable CVD, higher ucMGP is associated with lower odds of MAC in persons without diabetes, and higher odds of MAC in persons with diabetes. Future studies should determine whether ucMGP levels are associated with CVD events, and whether such associations differ by diabetes status.
PMCID: PMC2862076  PMID: 20015492
aortic stenosis; calcification; diabetes mellitus; matrix Gla protein; mitral annular calcification
25.  Can a cell have a soul? 
BMJ : British Medical Journal  2008;336(7653):1132.
PMCID: PMC2386625  PMID: 18483057

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