This study evaluated 177 asymptomatic individuals at intermediate risk for coronary artery disease. Coronary artery calcium scoring (CACS) using multidetector computed tomography was performed and correlated with measures of endothelial function and inflammatory markers. CAC was detected in 82 individuals (46%) with a median CACS of 143 units. Higher CACS correlated with older age, higher levels of interleukin-6, and worse endothelial function. In multivariate analysis, older age, higher interleukin-6 levels, and worse endothelial function were independently associated with presence of CAC. The study suggests testing endothelial function and inflammatory markers like interleukin-6 may improve cardiovascular risk assessment beyond traditional risk factors.
Improved diagnosis and prognosis using Decisions Informed by Combining Entities (DICE): results from the NHLBI-sponsored Women’s Ischemia Syndrome Evaluation (WISE)
Authors: Mark Doyle, Gerald M. Pohost, C. Noel Bairey Merz, Leslee J. Shaw, George Sopko, William J. Rogers, Barry L. Sharaf, Carl J. Pepine, Diane A. Vido-Thompson, Geetha Rayarao, Lindsey Tauxe, Sheryl F. Kelsey, Douglas Mc Nair, Robert W. Biederman
http://www.ncbi.nlm.nih.gov/pubmed/24400205
http://www.thecdt.org/article/view/3004
Extracorporeal membrane oxygenation assisted cardiopulmonary resuscitation (ECPR) is an effective therapy to improve outcomes for children who experience cardiopulmonary arrest. Survival after ECLS varies between 60% and 75%. For ECPR survival is lower, with 40% to 50% of children surviving ECPR. After ECPR good neurological outcomes are seen in 40% to 60% of children. This contrasts with adult patients where neurological outcomes after ECPR are poor. Given these findings the American Heart Association has included ECPR in their 2015 guidelines for children who experience an in hospital cardiac arrest (IHCA).
Improved diagnosis and prognosis using Decisions Informed by Combining Entities (DICE): results from the NHLBI-sponsored Women’s Ischemia Syndrome Evaluation (WISE)
Authors: Mark Doyle, Gerald M. Pohost, C. Noel Bairey Merz, Leslee J. Shaw, George Sopko, William J. Rogers, Barry L. Sharaf, Carl J. Pepine, Diane A. Vido-Thompson, Geetha Rayarao, Lindsey Tauxe, Sheryl F. Kelsey, Douglas Mc Nair, Robert W. Biederman
http://www.ncbi.nlm.nih.gov/pubmed/24400205
http://www.thecdt.org/article/view/3004
Extracorporeal membrane oxygenation assisted cardiopulmonary resuscitation (ECPR) is an effective therapy to improve outcomes for children who experience cardiopulmonary arrest. Survival after ECLS varies between 60% and 75%. For ECPR survival is lower, with 40% to 50% of children surviving ECPR. After ECPR good neurological outcomes are seen in 40% to 60% of children. This contrasts with adult patients where neurological outcomes after ECPR are poor. Given these findings the American Heart Association has included ECPR in their 2015 guidelines for children who experience an in hospital cardiac arrest (IHCA).
Impact of percutaneous coronary intervention on the levels of interleukin-6 and C-reactive protein in the coronary circulation of subjects with coronary artery disease
Comparison of clinical, radiological and outcome characteristics of ischemic ...MIMS Hospital
Here is the latest publication from the department of Neurology in the Journal of Neurology Research, titled, ’Comparison of Clinical, Radiological and Outcome Characteristics of Ischemic Strokes in Different Vascular Territories’ authored by Ashraf V Valappila, c, Dhanya T Janardhanana, Praveenkumar Raghunatha, Abdulla Cherayakkatb, Girija ASa
Background: Arterial stiffness is an independent predictor of cardiovascular disease. Independent of aging and other cardiovascular risk factors, arterial stiffness increases from the proximal to the distal arterial compartments. The overall aim of this work is to establish a longitudinal mechanical mapping of the arterial tree in healthy individuals.
Methods: We report preliminary data quantifying stiffness of the abdominal aorta (AAA), common carotid artery (CCA) and brachial artery (BA) in adolescents. In group-1 subjects (from Melbourne, Australia), cine-loops of the AAA and CCA B-mode data were digitally recorded, whereas in group-2 (from Montreal, Canada), cine-loops of the CCA and BA B-mode data were acquired at the same clinical evaluation. Arterial wall elastic moduli (EIBM) were estimated off-line using our proprietary non-invasive imaging-based biomarker algorithm(ImBioMark).
Role of Left Ventricular Mass Index Versus Left Ventricular Relative Wall Thi...Premier Publishers
In non-cardioembolic stroke patients, the cardiac manifestations of elevated blood pressure are of particular interest. The value of LV geometry in the prediction of cardiovascular risk is controversial. Many reports detected that left ventricular hypertrophy is independently associated with risk of ischemic stroke. The primary objective of this study was to identify the frequency of different patterns of altered left ventricular geometry in patients with non cardioembolic stroke, and to assess whether a significant number of patients will miss the diagnosis of LV remodeling if the left ventricular relative wall thickness(RWT) is not evaluated or reported. 100 patients were referred within 48 hours after an acute non cardioembolic ischemic stroke for a transthoracic echocardiogram. The echocardiographic findings were analyzed. Mean age was 61.86 ± 12.59 years, 45 % men. Concentric remodeling carried the highest frequency (43%), followed by normal pattern (27%), concentric hypertrophy (22%), and eccentric hypertrophy (8%). The frequency of abnormal left ventricular RWT (61.4%) was significantly higher than that of abnormal LVMI.
Impact of percutaneous coronary intervention on the levels of interleukin-6 and C-reactive protein in the coronary circulation of subjects with coronary artery disease
Comparison of clinical, radiological and outcome characteristics of ischemic ...MIMS Hospital
Here is the latest publication from the department of Neurology in the Journal of Neurology Research, titled, ’Comparison of Clinical, Radiological and Outcome Characteristics of Ischemic Strokes in Different Vascular Territories’ authored by Ashraf V Valappila, c, Dhanya T Janardhanana, Praveenkumar Raghunatha, Abdulla Cherayakkatb, Girija ASa
Background: Arterial stiffness is an independent predictor of cardiovascular disease. Independent of aging and other cardiovascular risk factors, arterial stiffness increases from the proximal to the distal arterial compartments. The overall aim of this work is to establish a longitudinal mechanical mapping of the arterial tree in healthy individuals.
Methods: We report preliminary data quantifying stiffness of the abdominal aorta (AAA), common carotid artery (CCA) and brachial artery (BA) in adolescents. In group-1 subjects (from Melbourne, Australia), cine-loops of the AAA and CCA B-mode data were digitally recorded, whereas in group-2 (from Montreal, Canada), cine-loops of the CCA and BA B-mode data were acquired at the same clinical evaluation. Arterial wall elastic moduli (EIBM) were estimated off-line using our proprietary non-invasive imaging-based biomarker algorithm(ImBioMark).
Role of Left Ventricular Mass Index Versus Left Ventricular Relative Wall Thi...Premier Publishers
In non-cardioembolic stroke patients, the cardiac manifestations of elevated blood pressure are of particular interest. The value of LV geometry in the prediction of cardiovascular risk is controversial. Many reports detected that left ventricular hypertrophy is independently associated with risk of ischemic stroke. The primary objective of this study was to identify the frequency of different patterns of altered left ventricular geometry in patients with non cardioembolic stroke, and to assess whether a significant number of patients will miss the diagnosis of LV remodeling if the left ventricular relative wall thickness(RWT) is not evaluated or reported. 100 patients were referred within 48 hours after an acute non cardioembolic ischemic stroke for a transthoracic echocardiogram. The echocardiographic findings were analyzed. Mean age was 61.86 ± 12.59 years, 45 % men. Concentric remodeling carried the highest frequency (43%), followed by normal pattern (27%), concentric hypertrophy (22%), and eccentric hypertrophy (8%). The frequency of abnormal left ventricular RWT (61.4%) was significantly higher than that of abnormal LVMI.
Evaluation Of Channel Function After Alteration Of Amino Acid Residues At The...Taruna Ikrar
Evaluation of channel function after alteration of amino acid residues at the pore center of KCNQ1 channel
The effect of the electrical charge or the size of the amino acid residue at the pore center of a slowly activation component of the delayed rectifier potassium channel: KCNQ1 was studied. K+ currents were measured after transfection of one of four KCNQ1 mutants: substituting Isoleucine with Lysine, Glutamate, Valine or Glycine and then transfected in COS-7 cells. Both the negatively- and positive charged residue I313 K and I313E showed a loss of function when expressed alone and a dominant negative suppression when co-expressed with wild type KCNQ1. When the site was substituted with the smallest neutral amino acid residue: I313G, there was a small reduction of current when transfected alone and a gain of function when co-transfected with the wild type. I313V showed no difference from the wild type. Changes of amino acid residue at the pore center of KCNQ1 may alter the channel function but this depends on the electrical charge or the size of amino acid residue.
Keywords: Long QT syndrome; Missense mutation; KCNQ1; IKs; Pore center; Amino acid residue
Abstract In the mammalian neocortex, excitatory neurons provide excitation in both columnar and laminar dimensions, which is modulated further by inhibitory neurons. However, our understanding of intracortical excitatory and inhibitory synaptic inputs in relation to principal excitatory neurons remains incomplete, and it is unclear how local excitatory and inhibitory synaptic connections to excitatory neurons are spatially organized on a layer-by-layer basis. In the present study, we combined whole cell recordings with laser scanning photostimulation via glutamate uncaging to map excitatory and inhibitory synaptic inputs to single excitatory neurons throughout cortical layers 2/3–6 in the mouse primary visual cortex (V1). We find that synaptic input sources of excitatory neurons span the radial columns of laminar microcircuits, and excitatory neurons in different V1 laminae exhibit distinct patterns of layer-specific organizationofexcitatoryinputs.Remarkably,thespatialextentofinhibitoryinputsofexcitatory neurons for a given layer closely mirrors that of their excitatory input sources, indicating that excitatory and inhibitory synaptic connectivity is spatially balanced across excitatory neuronal networks. Strong interlaminar inhibitory inputs are found, particularly for excitatory neurons in layers 2/3 and 5. This differs from earlier studies reporting that inhibitory cortical connections to excitatory neurons are generally localized within the same cortical layer. On the basis of the functional mapping assays, we conducted a quantitative assessment of both excitatory and inhibitory synaptic laminar connections to excitatory cells at single cell resolution, establishing precise layer-by-layer synaptic wiring diagrams of excitatory neurons in the visual cortex.
An inhibitory pull–push circuit in frontal cortexTaruna Ikrar
Push–pull is a canonical computation of excitatory cortical circuits. By contrast, we identify a pull–push inhibitory circuit in frontal cortex that originates in vasoactive intestinal polypeptide (VIP)-expressing interneurons. During arousal, VIP cells rapidly and directly inhibit pyramidal neurons; VIP cells also indirectly excite these pyramidal neurons via parallel disinhibition. Thus, arousal exerts a feedback pull–push influence on excitatory neurons—an inversion of the canonical push–pull of feedforward input.
A disinhibitory microcircuit initiates critical period plasticity in the visu...Taruna Ikrar
Earlysensoryexperienceinstructsthematurationofneuralcircuitry in the cortex1,2. This has been studied extensively in the primary visualcortex,inwhichlossofvisiontooneeyepermanentlydegrades corticalresponsivenesstothateye3,4,aphenomenonknownasocular dominance plasticity (ODP). Cortical inhibition mediates this process4–6,butthepreciseroleofspecificclassesofinhibitoryneurons in ODP is controversial. Here we report that evoked firing rates of binocular excitatory neurons in the primary visual cortex immediatelydropbyhalfwhenvisionisrestrictedtooneeye,butgradually return to normal over the followingtwenty-four hours, despite the fact that vision remains restricted to one eye. This restoration of binocular-like excitatory firing rates after monocular deprivation resultsfromarapid,althoughtransient,reductioninthefiringrates of fast-spiking, parvalbumin-positive (PV) interneurons, which in turncanbeattributedtoadecreaseinlocalexcitatorycircuitinput onto PV interneurons.This reduction in PV-cell-evoked responses after monocular lid suture is restricted to the critical period for ODPandappearstobenecessaryforsubsequentshiftsinexcitatory ODP. Pharmacologically enhancing inhibition at the time of sight deprivation blocks ODP and, conversely, pharmacogenetic reduction of PV cell firing rates can extend the critical period for ODP. Thesefindingsdefinethemicrocircuitchangesinitiatingcompetitive
plasticityduringcriticalperiodsofcorticaldevelopment.Moreover, they show that the restoration of evoked firing rates of layer 2/3 pyramidal neurons by PV-specific disinhibition is a key step in the progression of ODP.
Pten and eph b4 regulate the establishment of perisomatic inhibition in mouse...Taruna Ikrar
Perisomatic inhibition of pyramidal neurons is established by fast-spiking, parvalbuminexpressing interneurons (PV cells). Failure to assemble adequate perisomatic inhibition is thought to underlie the aetiology of neurological dysfunction in seizures, autism spectrum disorders and schizophrenia. Here we show that in mouse visual cortex, strong perisomatic inhibition does not develop if PV cells lack a single copy of Pten. PTEN signalling appears to drive the assembly of perisomatic inhibition in an experience-dependent manner by suppressing the expression of EphB4; PVcells hemizygous for Pten show an B2-fold increase in expression of EphB4, and over-expression of EphB4 in adult PV cells causes a dismantling of perisomatic inhibition. These findings implicate a molecular disinhibitory mechanism driving the establishment of perisomatic inhibition whereby visual experience enhances Pten signalling, resulting in the suppression of EphB4 expression; this relieves a native synaptic repulsion between PV cells and pyramidal neurons, thereby promoting the assembly of perisomatic inhibition.
A characteristic of the developing mammalian visual system is a brief interval of plasticity, termed the “critical period,” when the circuitry of
primary visual cortex is most sensitive to perturbation of visual experience. Depriving one eye of vision (monocular deprivation [MD]) during
the critical period alters ocular dominance (OD) by shifting the responsiveness of neurons in visual cortex to favor the nondeprived eye. A
disinhibitory microcircuit involving parvalbumin-expressing (PV) interneurons initiates this OD plasticity. The gene encoding the neuronal
nogo-66-receptor1(ngr1/rtn4r) is required to close the critical period.Herewecombinedmousegenetics, electrophysiology,andcircuitmapping
with laser-scanning photostimulation to investigate whether disinhibition is confined to the critical period by ngr1.We demonstrate that ngr1
mutant mice retain plasticity characteristic of the critical period as adults, and that ngr1 operates within PV interneurons to restrict the loss of
intracortical excitatory synaptic input following MD in adult mice, and this disinhibition induces a “lower PV network configuration” in both
critical-period wild-type miceandadult ngr1/mice.Wepropose that ngr1 limits disinhibition to close the critical period forODplasticityand
that a decrease in PV expression levels reports the diminished recent cumulative activity of these interneurons.
A disinhibitory microcircuit initiates critical period plasticity in the visu...Taruna Ikrar
Early sensory experience instructs the maturation of neural circuitry in the cortex1, 2. This has been studied extensively in the primary visual cortex, in which loss of vision to one eye permanently degrades cortical responsiveness to that eye3, 4, a phenomenon known as ocular dominance plasticity (ODP). Cortical inhibition mediates this process4, 5, 6, but the precise role of specific classes of inhibitory neurons in ODP is controversial. Here we report that evoked firing rates of binocular excitatory neurons in the primary visual cortex immediately drop by half when vision is restricted to one eye, but gradually return to normal over the following twenty-four hours, despite the fact that vision remains restricted to one eye. This restoration of binocular-like excitatory firing rates after monocular deprivation results from a rapid, although transient, reduction in the firing rates of fast-spiking, parvalbumin-positive (PV) interneurons, which in turn can be attributed to a decrease in local excitatory circuit input onto PV interneurons. This reduction in PV-cell-evoked responses after monocular lid suture is restricted to the critical period for ODP and appears to be necessary for subsequent shifts in excitatory ODP. Pharmacologically enhancing inhibition at the time of sight deprivation blocks ODP and, conversely, pharmacogenetic reduction of PV cell firing rates can extend the critical period for ODP. These findings define the microcircuit changes initiating competitive plasticity during critical periods of cortical development. Moreover, they show that the restoration of evoked firing rates of layer 2/3 pyramidal neurons by PV-specific disinhibition is a key step in the progression of ODP.
Characteristics of coronary artery ectasia and its association with carotid i...Premier Publishers
This study was conducted to uncover the relation between coronary artery ectasia (CAE) and markers of atherosclerosis. A total of 1611 coronary angiograms were prospectively examined to find out patients with CAE. Those patients were divided into 2 groups: Mixed CAE with stenotic coronary artery disease (CAD) “group 1” and pure CAE “group 2”. Two control groups of age-adjusted subjects were selected consecutively in a 1:1 fashion; one with normal coronaries “group 3” (Pure CAE: normal coronaries) and the other with obstructive CAD only “group 4” (Mixed CAE: obstructive CAD). All recruited subjects underwent carotid intima-media thickness (IMT) and high sensitivity C-reactive protein (hs-CRP) level measurements. Out of examined angiograms, 35 subjects showed mixed CAE “group 1” and 26 showed pure CAE “group 2”. Age and gender-adjusted logistic regression analysis model revealed that significant independent predictors for CAE were: hypertension, smoking, absence of DM and hs-CRP level > 3 mg/L. Mean carotid IMT was significantly higher in group 2 than group 3 and in group 4 than group 1 (1±0.1 versus 0.4±0.2 mm and 1.4±0.4 versus 1±0.2 mm respectively, P < 0.001 for both). Mean hs-CRP level was significantly higher in group 1 than group 4 and in group 2 than group 3 (7±2 versus 3±0.8 mg/L and 6±2 versus 1±0.6 mg/L respectively, P < 0.001 for both). We concluded that atherosclerosis may not be the only plausible explanation for CAE.
Functional genomics has led to an improvement of our understanding of CVD and can be translated to clinical utility. Gene-based pre-symptomatic prediction of illness, finer diagnostic sub-classifications and improved risk assessment tools will permit earlier and more targeted intervention. Pharmacogenetics will guide our therapeutic decisions and monitor response to therapy. Personalised medicine requires the integration of clinical information, stable and dynamic genomics and molecular phenotyping.
It is now possible to systematically search the entire human genome for common variants that are associated with a particular phenotype. (HGP, HAP MAP)
Predictors of Ischaemia and Outcomes in Egyptian Patients with Diabetes Mellitus Referred for Perfusion Imaging. Samir Rafla*, Ahmed Abdel-Aaty, Mohamed Ahmed Sadaka, Aly Ahmed Abo Elhoda and Ahmed Mohamed Shams
Novel Method for Automated Analysis of Retinal Images: Results in Subjects wi...Mutiple Sclerosis
Michele Cavallari, Claudio Stamile, Renato Umeton, Francesco Calimeri, and Francesco Orzi
Morphological analysis of the retinal vessels by fundoscopy provides noninvasive means for detecting and staging systemic microvascular damage. However, full exploitation of fundoscopy in clinical settings is limited by paucity of quantitative, objective information obtainable through the observer-driven evaluations currently employed in routine practice. Here, we report on the development of a semiautomated, computer-based method to assess retinal vessel morphology. The method allows simultaneous and operator-independent quantitative assessment of arteriole-to-venule ratio, tortuosity index, and mean fractal dimension. The method was implemented in two conditions known for being associated with retinal vessel changes: hypertensive retinopathy and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). The results showed that our approach is effective in detecting and quantifying the retinal vessel abnormalities. Arteriole-to-venule ratio, tortuosity index, and mean fractal dimension were altered in the subjects with hypertensive retinopathy or CADASIL with respect to age- and gender-matched controls. The interrater reliability was excellent for all the three indices (intraclass correlation coefficient ≥ 85%). The method represents simple and highly reproducible means for discriminating pathological conditions characterized by morphological changes of retinal vessels. The advantages of our method include simultaneous and operator-independent assessment of different parameters and improved reliability of the measurements.
Construction and Validation of Prognostic Signature Model Based on Metastatic...daranisaha
Colorectal Cancer (CRC) is a common malignant cancer with a poor prognosis. Liver metastasis is the dominant cause of death in CRC patients, and it often involves changes in various gene expression profiling. This study proposed to construct and validate a risk model based on differentially expressed genes between the primary and liver metastatic tumors from CRC for prognostic prediction.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
CDSCO and Phamacovigilance {Regulatory body in India}NEHA GUPTA
The Central Drugs Standard Control Organization (CDSCO) is India's national regulatory body for pharmaceuticals and medical devices. Operating under the Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, the CDSCO is responsible for approving new drugs, conducting clinical trials, setting standards for drugs, controlling the quality of imported drugs, and coordinating the activities of State Drug Control Organizations by providing expert advice.
Pharmacovigilance, on the other hand, is the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. The primary aim of pharmacovigilance is to ensure the safety and efficacy of medicines, thereby protecting public health.
In India, pharmacovigilance activities are monitored by the Pharmacovigilance Programme of India (PvPI), which works closely with CDSCO to collect, analyze, and act upon data regarding adverse drug reactions (ADRs). Together, they play a critical role in ensuring that the benefits of drugs outweigh their risks, maintaining high standards of patient safety, and promoting the rational use of medicines.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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1. Circ J 2008; 72: 778 – 785
Evaluation of Coronary Calcium Score by Multidetector
Computed Tomography in Relation to Endothelial
Function and Inflammatory Markers
in Asymptomatic Individuals
Mahmoud M. Ramadan, MD*,**; Essam M. Mahfouz, MD**; Gamal F. Gomaa, MD**;
Tarek A. El-Diasty, MD†; Louie Alldawi, MD*; Taruna Ikrar, MD*;
Ding Limin, MD*; Makoto Kodama, MD*; Yoshifusa Aizawa, MD*
Background Coronary calcification has been correlated with the presence and extent of coronary artery disease
(CAD), so in the present study the associations between coronary artery calcification score (CACS) and endothe-
lial dysfunction, as well as the important inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and
oxidized low-density lipoprotein (OxLDL), were studied in asymptomatic individuals at intermediate risk for
CAD.
Methods and Results The study group comprised 177 subjects (103 males) aged 50.6±5.9 years. CACS was
measured by multidetector computed tomography using the Agatston method. Endothelium-dependent flow-
mediated dilatation (FMD) and endothelium-independent nitroglycerin-mediated dilatation (NMD) were
measured by high-resolution external brachial ultrasound. Coronary artery calcification (CAC) was detected in
82 subjects (52 males), and the median CACS was 143 [31–311.25] units. After adjusting for gender and body
mass index, log (CACS +1) correlated positively with age (r=0.401, p<0.001) and IL-6 levels (r=0.442, p<0.001),
and negatively with FMD (r=–0.511, p<0.001). The correlations of log (CACS +1) with CRP and OxLDL levels,
and with NMD, were non-significant. In a multivariate-adjusted logistic regression model, age (odds ratio (OR) =
1.083 [1.014–1.156]), serum IL-6 level (OR=3.837 [2.166–6.798]) and FMD (OR=0.851 [0.793–0.913]) were
significantly and independently associated with CAC.
Conclusions Peripheral endothelial function inversely correlated with CACS, whereas IL-6 level was associ-
ated with CACS. Testing for endothelial function and IL-6 level may improve cardiovascular risk assessment
and help target the therapeutic strategies in asymptomatic patients at intermediate CAD risk. (Circ J 2008; 72:
778 – 785)
Key Words: C-reactive protein; Coronary calcification; Endothelial dysfunction; Interleukin-6; Oxidized low-
density lipoprotein
C
oronary artery calcification (CAC) is an anatomic lium-independent nitroglycerin-mediated dilatation (NMD)
disease marker that has been correlated with the of the brachial artery via external brachial ultrasound. How-
presence and extent of coronary artery disease ever, only 2 previous studies5,6 have investigated the rela-
1
(CAD). Fortunately, noninvasive detection of CAC and tionship between the extent of CAC and endothelial func-
quantitative estimation of its score (CACS) can be done by tion in subjects along the whole risk spectrum for CAD, and
multidetector computed tomography (CT). they reported conflicting results. Therefore, in this study we
Endothelial dysfunction is now recognized as a key early tested the hypothesis that CACS is associated with endo-
event in atherogenesis, because it is linked to CAD risk3 and
2 thelial dysfunction as reflected by FMD and NMD of the
4
future adverse cardiovascular events. It is now possible to brachial artery, focusing on asymptomatic subjects at inter-
indirectly test endothelial function by means of endothelium- mediate risk for CAD, which is the category of patients of
dependent flow-mediated dilatation (FMD) and endothe- particular interest for the purposes of primary prevention
and risk identification and reduction.
Both C-reactive protein (CRP) and interleukin-6 (IL-6)
(Received August 13, 2007; revised manuscript received December 3, 7,8
2007; accepted December 13, 2007)
are closely associated with CAD pathogenesis. Similarly,
*Division of Cardiology, First Department of Internal Medicine, oxidized low-density lipoprotein (OxLDL) is believed to
9
play a key role in the development of atherosclerosis. How-
Niigata University Graduate School of Medical and Dental Sciences,
Niigata, Japan, **Department of Cardiology, Mansoura Faculty of ever, studies of CAC in relation to inflammatory markers
Medicine and †Department of Radiology, Mansoura Urology and (other than CRP) are generally scarce. To test whether im-
Nephrology Center, Mansoura University, Mansoura, Egypt portant inflammatory markers, such as CRP, IL-6, and
Mailing address: Mahmoud M. Ramadan, MD, Division of Cardiolo-
gy, Niigata University Hospital, 1-754 Asahimachi Dori, Niigata 951-
OxLDL, are related to coronary atherosclerotic burden (as
8510, Japan. E-mail: amamod@med.niiagata-u.ac.jp defined by CACS) beyond established risk factors in
All rights are reserved to the Japanese Circulation Society. For per- asymptomatic individuals at intermediate risk for CAD, we
missions, please e-mail: cj@j-circ.or.jp sought to determine the benefit of including information on
Circulation Journal Vol.72, May 2008
2. CAC and Endothelial Dysfunction/Inflammatory Markers 779
endothelial function and inflammatory markers in the cur- Laboratory Methods
rent models of CAD risk assessment, prevention, and treat- On the day of screening after a 12-h fast, antecubital
ment used for this category of patients. venous blood samples were drawn into vacuum tubes with
appropriate additives for assessment of glucose, lipids, liver
function, complete blood count, serum electrolytes, serum
Methods creatinine, and uric acid. Serum high-sensitive CRP was
Study Design and Participants measured by particle-enhanced immunoturbidometric latex
From January, 2002 to February, 2004, we enrolled 177 agglutination assay (Dade Behring, Newark, DE, USA)
asymptomatic, ethnically Middle Eastern Egyptians of both and IL-6 was measured by high-sensitivity immunoassay
genders who were in the intermediate-risk category accord- (Quantikine human IL-6, R&D Systems, Minneapolis,
ing to the 10-year Framingham Study risk score (FRS) for MN, USA). OxLDL was measured by a sensitive ELISA
CAD events. We used the risk factor information to calcu- method specific for detecting malondialdehyde-modified
late the risk of coronary events during a 10-year period LDL. 11
according to the FRS calculation algorithm10 and included
only those with a 10–20% risk of developing CAD. Endothelial Measurements
Subjects aged 40–59 years with at least 1 coronary risk FMD of the brachial artery following transient ischemia
factor were recruited from an internal database comprising is a noninvasive method of assessing endothelial function,
more than 6,000 outpatients of Mansoura University Hos- which we performed according to the guidelines described
pital, Mansoura, Egypt, who were asymptomatic for CAD. 12
by Corretti et al. Following an overnight fast, and approxi-
Initially, 965 subjects were invited to participate in our mately 1 h after the CT scanning was completed, the subject
study by letter (another was sent in cases of non-response) remained supine (although this is not superior to the seated
and telephone calls (whenever possible). Agreement to par- position13) while the right brachial artery was scanned in
ticipate was received from 786 subjects, 48 of whom later the longitudinal section 3–5 cm above the antecubital fossa.
withdrew. Thus, 738 subjects aged 40–59 years with at least Brachial artery diameter was measured on B-mode ultra-
1 coronary risk factor remained and underwent the prelimi- sound images using a 7.0-MHz linear-array transducer and
nary evaluation. Subjects were also excluded if they had a a standard Acuson 128 XP/10 system (Mountain View, CA,
history of ischemic heart disease. USA). After recording baseline measurements, the cuff was
All subjects were interviewed to complete a detailed placed proximal to the scanned section of brachial artery
health questionnaire. Family history of CAD was pertinent and inflated to ≥50 mmHg above the subject’s systolic ABP
if established CAD was present in a first-degree male rela- for 5 min to create forearm ischemia. Subsequently, the
tive aged ≤55 years or female relative aged ≤65 years of cuff was deflated and the arterial diameter was measured
age. Current or past history of smoking was relevant if the 60 s after deflation. Endothelium-dependent dilatation was
subject had smoked >10 cigarettes/day for at least 1 year. expressed as the percentage change in brachial artery diam-
Hypertension was defined as systolic pressure ≥140 mmHg, eter from baseline to reactive hyperemia.
diastolic pressure ≥90 mmHg, or current use of antihyper- Endothelium-independent dilatation was assessed by
tensive medication. Diabetes was defined as fasting glucose measuring changes in brachial artery diameter after sublin-
>125 mg/dl (if untreated) or previous physician diagnosis gual nitroglycerin administration. Following endothelium-
and treatment with diet, oral hypoglycemic drugs, or insulin. dependent measurements for 15 min, baseline resting images
Body mass index was calculated as weight/height2 (kg/m2); were again taken, followed by sublingual administration of
and obesity was defined as body mass index ≥30 kg/m2. Hy- 0.5 mg nitroglycerin; measurements were repeated 3 min
percholesterolemia was defined as a total cholesterol level later. Endothelium-independent dilatation was expressed as
>200 mg/dl or the use of cholesterol-lowering medications. the percentage change in brachial artery diameter from
Participants were given appointments to undergo the baseline to that following sublingual nitroglycerin adminis-
planned investigations, stressing an overnight fast (includ- tration.
ing stoppage of all medications) for at least 12 h prior to
testing. Resting systolic and diastolic arterial blood pres- Coronary Calcium Imaging and Quantification
sures (ABP) were recorded by mercury sphygmomanometer CAC scanning was performed using an 8-slice multi-
as the average of the last 2 of 3 readings, each 5 min apart detector-row CT scanner (Light Speed Plus CT scanner,
with the subject seated. Standard 12-lead electrocardio- General Electric Medical Systems, Milwaukee, WI, USA)
grams (ECGs) were recorded to evaluate the presence of with prospective ECG gating using sequential data acquisi-
left ventricular hypertrophy (LVH), which was diagnosed as tion. Scans were prospectively initiated at 50% of the RR
Cornell voltage duration product >2,440 mV/ms. Addition- interval. CT scanning was postponed if the resting pulse
ally, 2-dimensional echocardiographic examination was rate exceeded 75 beats/min, in which case controlling the
preformed and the left ventricular mass (g) was calculated pulse rate with intravenous -blocker was attempted and
according to the method recommended by the American the scan was performed 20 min later if this was successful.
Society of Echocardiography [LV mass =0.8 (1.04 [LVDd + Forty-eight consecutive non-overlapping 2.5 mm-thick
IVST + PWT]3 – LVDd3) + 0.6, where LVDd = left ventricu- slices were acquired, with simultaneous acquisition of 8
lar diastolic dimension (mm), IVST = interventricular sep- slices (140 kV, 150 mA, gantry rotation time 500 ms, and
tum thickness (mm), and PWT = posterior wall thickness temporal resolution 330 ms). All sections were reviewed by
(mm)] followed by indexing to body surface area (m2). 2 experienced radiologists who were unaware of all clinical
The study protocol was reviewed and accepted by the data. Image review and CAC scoring were done at a special
local Ethical Review Board of the Mansoura University Advantage Window 4.1 workstation (General Electric
Faculty of Medicine, and written informed consent was Medical Systems) using SmartScore software.
given by each participant. CACS was quantified by the method of Agatston et al14
in which CAC is defined as an area of at least 2 contiguous
Circulation Journal Vol.72, May 2008
3. 780 RAMADAN MM et al.
Table 1 Baseline Characteristics and Comparisons of Subjects With and Without CAC
Total CAC-positive CAC-negative
p value
(n=177) (n=82) (n=95)
History
Age (years) 50.6±5.9 52.3±5.1 48.7±6.1 <0.001**
Gender
M 103 (58.2%) 52 (63.4%) 51 (53.7%)
0.248
F 74 (41.8%) 30 (36.6%) 44 (46.3%)
Medications
ACEIs/ARBs 99 (55.9%) 45 (54.9%) 54 (56.8%) 0.912
Aspirin 108 (61.0%) 49 (59.8%) 59 (62.1%) 0.869
-blockers 34 (19.2%) 19 (23.2%) 15 (15.8%) 0.293
Calcium-channel blockers 46 (26.0%) 20 (24.4%) 26 (27.4%) 0.781
Diuretics 86 (48.6%) 41 (50.0%) 45 (47.4%) 0.843
Statins 27 (15.3%) 12 (14.6%) 15 (15.8%) 0.997
CAD risk factors
CAD family history 81 (45.8%) 40 (48.8%) 41 (43.2%) 0.551
Current smoking 68 (38.4%) 27 (32.9%) 41 (43.2%) 0.215
Diabetes mellitus 117 (66.1%) 56 (68.3%) 61 (64.2%) 0.681
Hypertension 108 (61.0%) 53 (64.6%) 55 (57.9%) 0.446
Obesity (BMI ≥30 kg/m2) 79 (44.6%) 37 (45.1%) 42 (44.2%) 0.903
10-year FRS 15.2 [11.5–17.9] 17.7 [11.9–18.4] 14.2 [11.0–16.6] 0.045*
Anthropometric/medical measurements
Body weight (kg) 82.3±15.8 83.2±13.9 81.6±17.3 0.527
Height (cm) 167.0±8.2 167.7±7.8 166.4±8.4 0.284
BMI (kg/m2) 29.7±6.1 29.7±5.4 29.6±6.7 0.939
Systolic ABP (mmHg) 135 [125–155] 137.5 [125–155] 135 [125–155] 0.807
Diastolic ABP (mmHg) 90 [80–100] 90 [80–100] 90 [75–100] 0.579
Mean ABP (mmHg) 105 [95–117.5] 104.5 [95–117.1] 105 [93.3–118.3] 0.641
Laboratory measurements
Fasting glucose (mg/dl) 168.0±53.3 172.0±49.0 164.0±56.7 0.321
Hemoglobin A1c (%) 6.02±2.05 6.09±2.12 5.95±1.98 0.637
Total cholesterol (mg/dl) 196 [166.8–266.2] 210.5 [169.4–266.5] 180 [162–266] 0.121
HDL-cholesterol (mg/dl) 39.4±8.5 38.6±8.1 40.1±8.8 0.267
LDL-cholesterol (mg/dl) 120 [95.2–190.1] 133.1 [103.8–198] 108.8 [90.6–189] 0.019*
Triglycerides (mg/dl) 153 [111–199] 149 [107.5–199.3] 159 [116–198] 0.496
CRP (mg/L) 2.19±1.43 2.42±1.44 1.99±1.39 0.043*
Interleukin-6 (pg/ml) 1.92±0.866 2.31±0.932 1.59±0.643 <0.001*
OxLDL (U/L) 188.8±53.9 190.0±54.7 187.8±53.5 0.784
ECG data and Echo measurements
LVH on ECG 52 (29.4%) 20 (24.4%) 32 (33.7%) 0.235
Fractional shortening (%) 35 [32–38] 35.5 [33–39] 35 [32–37] 0.121
Ejection fraction (%) 65.7±6.6 66.1±6.7 65.3±6.5 0.384
LVMI (g/m2) 58.0±18.8 56.9±17.2 58.9±20.2 0.479
Endothelial measurements
FMD (%) 9.9±7.2 6.7±4.6 12.6 ±7.9 <0.001**
NMD (%) 13.4±5.7 12.8±5.7 13.9±5.6 0.164
Values are mean ± SD, median [interquartile range] or number of subjects (%).
Statistical significance at *p<0.05 and **p<0.001.
CAC, coronary artery calcification; ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin-II receptor blockers; CAD,
coronary artery disease; BMI, body mass index; FRS, Framingham Study risk score; ABP, arterial blood pressure; HDL, high-density
lipoprotein; LDL, low-density lipoprotein; CRP, C-reactive protein; OxLDL, oxidized low-density lipoprotein; ECG, electrocardiogra-
phy; Echo, echocardiography; LVH, left ventricular hypertrophy; LVMI, left ventricular mass index; FMD, flow-mediated dilatation;
NMD, nitroglycerin-mediated dilatation.
pixels with a CT density threshold of 130 Hounsfield units. half of the study participants had a CACS of 0; as such, it
CACS was calculated by multiplying the area of CAC by a was resistant to normalization by log transformation and
factor rated 1–4 dictated by the maximum CT density with- other techniques. Therefore, the CACS values were grouped
in that lesion. CACS values were grouped into 4 ascending into a dichotomous variable (ie, presence of any calcifica-
CAC grades: 0 (absent; rating =0), 1–99 (mild; rating =1), tion or total absence of CAC) for use in logistic regression.
100–399 (moderate; rating =2) and ≥400 (severe; rating =3). Comparisons of means and medians of continuous data
For each patient, CACS can be calculated for each of the across a factor with 2 levels were done by Student’s t-test
major coronary arteries: left main, left anterior descending, and the Mann-Whitney U-test for normal and skewed data,
left circumflex, and right coronary arteries; the sum of respectively. Comparisons of group means across CAC
these gives the total CACS. grades were done by 1-way analysis of variance (ANOVA),
with post-hoc tests (Scheffe or Games-Howell). Compari-
Statistical Analysis sons of proportions were done by the 2 test. The correla-
Normality of distribution of the different variables was tions between CACS and the continuous variables’ values
assessed by the 1-sample Kolmogorov-Smirnov test. The were assessed by the Spearman test. A 2-sided significance
distribution of CACS was markedly skewed, because about level of 0.05 was used for all analyses, which were con-
Circulation Journal Vol.72, May 2008
4. CAC and Endothelial Dysfunction/Inflammatory Markers 781
Table 2 Mean Distribution of Continuous Variables Across Ordinal CAC Grades
CAC grade
Absent Mild Moderate Severe p value p-for-
[CACS=0] [CACS=1–99] [CACS=100–399] [CACS ≥400] (ANOVA) trend
(n=95) (n=34) (n=33) (n=15)
Age (years) 48.7±6.1a,b 51.4±5.4 52.2±4.7 54.7±4.9 <0.001** <0.001**
FMD (%) 12.6±7.9a,b,c 8.5±4.8a 6.1±4.3 4.2±3.6 <0.001** <0.001**
Interleukin-6 (pg/ml) 1.59±0.64a,b,c 2.08±0.71 2.34±1.01 2.73±1.10 <0.001** <0.001**
CRP (mg/L) 1.99±1.39 2.61±1.68 2.18±1.19 2.53±1.38 0.125 0.129
OxLDL (U/L) 187.8±53.5 191.2±57.7 182.5±50.9 203.9±56.4 0.631 0.641
NMD (%) 13.9±5.6 13.5±6.8 12.1±4.6 12.7±5.3 0.408 0.127
ap<0.05 vs severe coronary calcification group; bp<0.05 vs moderate coronary calcification group; cp<0.05 vs mild coronary cal-
cification group.
Statistical significance at **p<0.001.
ANOVA, analysis of variance; CACS, CAC score. Other abbreviations as in Table 1.
ducted using SPSS 15 for Windows (SPSS Inc, Chicago, stepwise logistic regression model: age, 10-year FRS, LDL-
IL, USA). cholesterol, CRP, IL-6, and FMD. This model was also ad-
justed for the essential confounders (gender and body mass
index). We found that age, IL-6 levels, and FMD percent-
Results age values were significantly and independently associated
We studied 177 subjects (103 males, 74 females) aged with the presence of CAC (Table 3). The final logistic
40–59 years. CAC was detected in 82 subjects (46% of regression model proved to be highly significant (p<0.001),
sample: 52 males, 30 females). In the CAC-positive group, with good calibration (Hosmer-Lemeshow Goodness-of-fit
the CACS range was 10–1,901 Agatston units (median 2 =6.33, p=0.610) and high discriminative power (C-statis-
[interquartile range] of 143 [31–311.25] units). The median tic=0.85 [0.80–0.91]; p<0.001, Nagelkerke R2 =0.45). The
CACS was higher in males than in females (2 [0–202] vs 1 model’s correlation matrix was carefully checked to avoid
[0–97.5] units), but the difference was not significant (p= collinearity, which was excluded on the basis of reasonable
0.117). Baseline characteristics and comparisons of subjects correlations (generally, r<±0.5).
with and without CAC are shown in Table 1. The CAC-
positive group showed significantly higher means (medians)
for age, 10-year FRS, LDL-cholesterol, CRP, and IL-6 Discussion
level than the CAC-negative group, but significantly lower CAC, which occurs exclusively in atherosclerotic arte-
mean FMD. ries and is absent in normal ones, is an early step in the
Variance analysis (Table 2) revealed significant differ- 15
development of atherosclerosis. Quantification of CACS
ences in the mean distribution of age, serum IL-6 levels, provides accurate assessment of the overall atherosclerotic
and FMD percentage values across CAC grades, reflecting plaque burden in the coronary tree;1 however, calcium does
the possible associations of these variables with the incre- not concentrate exclusively at sites with severe coronary
ment of CACS categories. The differences in mean serum 16
artery stenoses. There is no proven relationship between
CRP levels, NMD percentage values, and OxLDL levels CAC and either vulnerable (complications-prone) plaque17
were insignificant. Obviously, we found a significant trend 18,19
or the probability of plaque rupture. However, pathology
with increasing mean age and IL-6 level, and a reciprocal studies have shown that the extent of CAC within plaques
decremental trend of FMD as the CAC grade increased (p- tends to be related to the presence of healed plaque rup-
for-trend <0.001). 20
tures. Moreover, vulnerable plaques tend to be those with
After adjusting for gender and body mass index, signifi- less extensive calcium deposits and are frequently seen in a
cant positive correlations were found between log (CACS + 20
spotty distribution, a finding supported by intravascular
1) values and age (r=0.401; p<0.001), 10-year FRS (r= ultrasound studies of patients with acute coronary syn-
0.453; p=0.002) [Fig 1A], and serum IL-6 levels (r=0.442; 21
dromes. In addition, a recent study that used spectral
p<0.001) [Fig 1B]. On the other hand, CACS correlated analysis of intravascular ultrasound radiofrequency data has
negatively with FMD (r=–0.511; p<0.001) [Fig 1C]. CACS reported an association between dense calcium deposition
correlations with serum CRP levels (r=0.111, p=0.221) and culprit coronary atherosclerotic plaques with negative
[Fig 1D], OxLDL levels (r=0.013, p=0.866) [Fig 1E], NMD 22
remodeling. Recently, Motoyama et al proposed spotty
values (r=–0.124; p=0.203) [Fig 1F] and the other continu- calcification as 1 of the triad CT features characterizing
ous variables were insignificant. The correlations between culprit lesions associated with acute coronary syndromes. 23
FMD values and the biomarkers (adjusted for age, gender, The present study shows clearly the incremental value of
and body mass index) were insignificant (r=–0.058, p= studying CAC in the present, and the results suggest that it
0.444 for CRP; r=–0.089, p=0.241 for IL-6; r=–0.093, p= may have more widespread use for a variety of indications
0.223 for OxLDL), and the same was found for the correla- in the future. In fact, CAC scoring may be able to globally
tions of NMD values to these biomarkers (r=0.011–0.049; define a patient’s CAD event risk by virtue of its strong
p=0.523–0.886). association with total coronary atherosclerotic disease bur-
Following univariate logistic regression analysis for each den, as shown by correlation with pathologic specimens. 1,24
independent variable against the CAC-positive outcome, Asymptomatic individuals with an intermediate FRS (be-
the following were associated with CAC presence at p≤0.1 tween 10 and 20% 10-year risk of estimated coronary
(the entry threshold), and were thus included in the final events) may be reasonable candidates for CAD testing
Circulation Journal Vol.72, May 2008
5. 782 RAMADAN MM et al.
Fig 1. Scatter plots showing the correlations between log (CACS +1) and 10-year Framingham Study risk score (A),
interleukin-6 levels (B), flow-mediated dilatation percentage values (C), C-reactive protein levels (D), oxidized low-den-
sity lipoprotein levels (E), and nitroglycerin-mediated dilatation percentage values (F). CACS, coronary artery calcification
score.
Circulation Journal Vol.72, May 2008
6. CAC and Endothelial Dysfunction/Inflammatory Markers 783
Table 3 Results of Final Multivariate Logistic Regression Model Used to Test the Independent Association of the Input
Variables With Positive Coronary Calcification Outcome
-coefficient OR 95%CI for OR p value
Age (years) 0.079 1.083 1.014–1.156 0.018*
FMD (%) –0.162 0.851 0.793–0.913 <0.001**
Interleukin-6 (pg/ml) 1.345 3.837 2.166–6.798 <0.001**
10-year FRS 0.022 1.022 0.975–1.071 0.361
LDL-cholesterol (mg/dl) –0.003 0.997 0.988–1.005 0.445
CRP (mg/L) 0.096 1.101 0.846–1.431 0.476
Statistical significance at *p<0.05 and **p<0.001.
OR, odds ratio; CI, confidence interval. Other abbreviations as in Table 1.
using CAC as a potential means of modifying risk predic- have had a significant influence.
25
tion and altering therapy. This category of patients repre- Park et al found that CACSs and plasma CRP levels pro-
sents the population of particular interest for the purpose of vided incremental information regarding the risk of clinical
primary prevention and risk identification and reduction. cardiovascular events in asymptomatic non-diabetic sub-
We found CAC in 46% of subjects in the aforementioned 30
jects. In our study, we found a borderline significant asso-
category. In addition, we found a significant moderate ciation between CRP level and CAC presence per se, which
association between CAC/endothelial dysfunction and 1 failed to persist after multivariate adjustment, denoting a
(IL-6), but not the other (CRP, OxLDL), inflammatory possible effect of the other confounders. Similar to our re-
markers we tested. sults, the Study of Inherited Risk of Coronary Atheroscle-
It has been reported that age and gender are the strongest rosis (SIRCA) documented a gender-specific association
26
clinical correlates of CAC. Also, high CAC prevalence is between CRP and CAC that was completely lost after
reported in subjects >60 years regardless of the presence of 31
adjustment for measures of adiposity. Although many
27
risk factors. In agreement those findings, 26,27 we found an studies have reported conflicting results about the relation-
independent association between age and CAC even before ship between CRP and CAC in asymptomatic individuals,
the 7th decade. The proportion of CAC-positive subjects the importance of the SIRCA study derives from its use of
rose steeply in the 6th decade (56%) compared with the 5th the largest sample set to date.
(34%) and 4th (10%) decades (p-for-trend =0.030). In con- To our knowledge, only 1 study has evaluated the rela-
trast to the other studies,26,27 we did not find a significant tionship between OxLDL and CACS in patients with CAD
influence of gender upon CAC presence. 32
and documented a non-significant correlation. In our study,
To the best of our knowledge, only 2 prior studies have we investigated this relationship in asymptomatic subjects
investigated the association of CAC (by electron-beam CT) with a relatively larger sample size than that of Sherer et
with endothelial function in symptomatic5 and asympto- 32
al. We did not find any significant association between
matic6 individuals along the entire CAD risk spectrum. Our OxLDL and CACS. Although the presence and magnitude
results reveal a significant association between endothelial 33
of CAC is related to the level of LDL-cholesterol, it seems
dysfunction (ie, reduced FMD) and CAC after multivariate that the oxidation of LDL might not significantly partici-
adjustment, which is in accordance with the results of pate in the process of CAC pathogenesis.
5
Huang et al, but contradictory to the findings of Kullo et al.6 A novel result reported here is the association of IL-6 not
The reasons for the discrepancies with the latter study are only with CACS in the univariate and variance analyses, but
not fully clear; however, differences in study design, also as an important independent correlate of CAC in the
methods, and population characteristics may be possible multivariate analysis. Thus, the possible role of IL-6 in the
factors. In our study, the lack of association between CACS CAD/CAC interaction matrix may be a reasonable ratio-
and NMD (which reflects endothelium-independent dilata- nale for its inclusion in cardiovascular risk prediction and
tion via passive donation of nitric oxide), together with the therapeutic algorithms. However, to address why only IL-6,
emergence of FMD as an independent inverse correlate of but neither CRP nor OxLDL, was associated with CAC, we
CAC, signify a possible role of abnormal endothelium in the must consider the mechanism of vascular calcification. It is
pathogenesis of CAC, which may involve pathways other now known that vascular calcification is a regulated proc-
than reduced nitric oxide release. In this respect, one might 34
ess similar in many respects to bone formation. Also, cells
consider for future CAC studies using biomarkers that are with osteoblastic characteristics, termed “calcifying vascu-
more specifically linked with endothelial function, such as lar cells”, have been isolated from the vascular media. 35,36
looking at the levels of CD34+KDR+ endothelial progenitor Well-documented findings suggest that differentiation of
cells28 in peripheral blood in this category of patients. In vascular cells plays a pivotal role by proceeding along
fact, the use of this cellular marker would unify the com- osteogenic and chondrogenic lineages, resulting in calcified
plex interactions of multiple negative factors and may yield vascular tissues.35,37 One may hypothesize that an increase
a better picture of in vivo mechanisms. Budoff et al29 ex-
28 of IL-6 level would induce the latter process, whereas a
amined the association of CACS with brachial artery mea- similar induction by CRP or OxLDL may not be sufficient-
sures (distensibility and resistance) in 201 asymptomatic ly strong in asymptomatic individuals with subclinical
subjects (70% men) referred by physicians for risk evalua- atherosclerosis.
tion using electron-beam CT scans. They demonstrated a The present findings support the utility of including
fair correlation between decreasing brachial artery mea- information on endothelial function and serum IL-6 level in
surements and increasing CACS. However, that study did current methods of global risk assessment and in practice
not evaluate FMD, NMD, or inflammatory markers, so the guidelines for asymptomatic patients in the intermediate-
results were not adjusted for these biomarkers, which might risk category of the 10-year FRS for CAD events. Measures
Circulation Journal Vol.72, May 2008
7. 784 RAMADAN MM et al.
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