A Multi-Layer Non-Newtonian Model of Cardiovascular Inflammation

Cellular functions related to the maintenance of homoeostasis are regulated by shear forces sensed by endothelial cells. The endothelial cells sense local changes in shear stress. The resulting signals are either transduced into chemical responses or transmitted to the surroundings to regulate the cellular activity.

In the current literature, models of blood flow applied to the characterization of atherosclerotic plaques consider blood as a Newtonian fluid because of the characteristic length of the domain. At predilection sites for plaque deposition, the diameter of the blood particles is much smaller than the normal arterial diameter. However, under disease condition, the proportions can dramatically change due to a reduction greater than 80% in the arterial cross-section, in cases of severe stenosis. Here we show that in diseased arteries, the local particle concentration can peak at locations associated to high inflammation.

The Standing Acoustic Wave Principle within the Frequency Analysis of Acoustic Signals in the Cochlea

The organ of hearing is responsible for the correct frequency analysis of auditory perceptions coming from the outer environment. The article deals with the principles of the analysis of auditory perceptions in the cochlea only, i.e., from the overall signal leaving the oval window to its decomposition realized by the basilar membrane. The paper presents two different methods with the function of the cochlea considered as a frequency analyzer of perceived acoustic signals.

First, there is an analysis of the principle that cochlear function involves acoustic waves travelling along the basilar membrane; this concept is one that prevails in the contemporary specialist literature. Then, a new principle with the working name “the principle of standing acoustic waves in the common cavity of the scala vestibuli and scala tympani” is presented and defined in depth. According to this principle, individual structural modes of the basilar membrane are excited by continuous standing waves of acoustic pressure in the scale tympani.

Dose Optimization Studies by Selecting Kilovoltage in Oncologic Chest CT

In this work we have studied the adequacy of dose levels of irradiation in oncologic chest CT obtained in our daily practice. The secondary objective was to evaluate the effect on radiation dose of individual adjustment of kilovoltage in thoracic multidetector row computed tomography (MDCT) images acquired with both single and dual-source technology. The impact of lowering the kilovoltage in the diagnostic quality of these studies was also evaluated. 161 patients were included in the study. CT examinations were performed using two different equipments: a conventional CT scanner and a dual-source computed tomography. The average values of dose length product (DLP) obtained in our daily practice meet the recommendations of the existing referral guidelines. Lower values can be achieved through individual adjustment of kilovoltage and with dual-source CT technology, maintaining the diagnostic quality of these studies.

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A Revolutionary Method of Treatment

A tumor without a supporting network of blood vessel formation is like a car without wheels-it’s not going anywhere! But the multiple hemangiopericytoma type of brain tumors I’ve been shackled with over the last fourteen years were multiplying rapidly in the cancer lane and were driving me one hundred and ten miles an hour to my grave!

That was until suddenly, in early March, 2003, when Providence unexpectedly whisked me away from my home in Burbank, CA and guided me directly to the one person, who was to change my life forever so that I would be free of any new or recurring tumors of any variety, have a quality life and even have it extended several years! He is Mr. Nick Kostovic, a pioneer and visionary in energetic medicine, and his health clinic, the Bio Technological Health Center, Inc., in San Pedro, California is where he not only killed my malignant brain tumors, but where this brilliant, caring therapist is helping heal my malignant brain tumors, but where this brilliant, caring therapist is helping heal many other patients by eradicating other treacherous life threatening diseases such as diabetes, cancer, Lou Gehrig's Disease (ALS), Parkinson’s, MS, strokes and more.

Visually Guided Horizontal Saccades under the Double-Step Paradigm

Visually goal-oriented saccades were recorded under the double-step paradigm. Data were analyzed to produce parameter estimates using the system identification technique for a 3rd-order linear horizontal saccadic eye movement model. Statistical analysis of a large human saccade data set provided reliable conclusions of the response properties. Saccade amplitude, latency and inter-saccade interval were discussed with time delay, indicating the parallel programming mechanism, which two saccades to different targets could be programmed simultaneously. The results of neural input estimations suggested that the double-step visual targets may affect the synchronous firing of the saccade responsible neurons in the superior colliculus.

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Stimuli-Responsive Hydrogels Bearing αamino acid Residues: a Potential Platform for Future Therapies

Vinyl hydrogels bearing α-amino acid residues have been explored as platforms for the treatment of cancer, glaucoma and mood disorder therapies. Ionic/ionizable groups of the L-valine, L-phenylalanine and L-histidine residues are able to modify the swelling properties of the hydrogel on the basis of their thermodynamic characteristics.

Greater basicity constants of functional groups improve a greater loading of the drug and a longer sustained-release pattern. The pH and the temperature affect the swelling of the hydrogel and increase ‘on demand’ the drug availability. A further stimulus based on alternating magnetic fields can be applied on hydrogels containing embedded magnetic nanoparticles used for site-specific controlled drug delivery. The diffusion process for the in vitro release of the drug (cisplatin, doxorubicin, pilocarpine, trazodone, citalopram and paroxetine) from the drug loaded hydrogels is mainly controlled by the drug-polymer interaction, that in the meanwhile preserves its bioactivity. The different interaction strength between the drug and the polymer may be a strategy to develop suitable capsules for long-term therapies.

Human-Organoid Models: Accomplishments to Salvage Test-Animals

Late stage attritions in drug discovery are costly and consuming. Improbable response of test molecules acquired in non-human systems is attributed to be the major cause of clinical failures. While conventional in vitro methods of drug discovery do not truly represent the human system, the animal models used for in vivo validation are also genetically and phenotypically distant from humans. 

However, recent developments in organoid culture are motivating and elevate hopes for replacing test animals with artificial human tissue models. Possibility of creating functional tissue ex vivo has a potential to revolutionize the way human therapeutics is perceived. Not only will it bridge the gap between drug development and its clinical efficacy but also help strategizing regenerative medicine. Successful human-tissue surrogates would liberate test animals or at least minimize their use for research purposes. Potential drug candidates tested on human-tissue equivalents are expected to generate clinically much more relevant data. Here we deliberate upon the options and possibilities of accomplishing human organoid models for in vitro testing and their significance in therapeutics.

Cardiopulmonary Resuscitation as a Graduation Requirement for Biomedical Engineering Students

At the end of a mountain road in Austria during the summer of 2003, I waited for a boat with my family on a dock at a large lake. Suddenly I saw a man fall to the side walk. His skin had turned that ashen blue color, and it was clear to me that he was in cardiac arrest. There was a crowd of more than 75 persons just standing and looking at him. 

I knew what to do when there was no detectable pulse or breathing. Cardio-Pulmonary Resuscitation (CPR) chest compressions were started immediately. His skin color returned to nearly normal. After a few minutes, a single bystander came up and said they knew how to do breaths. At that time, recommendations were for intermittent breathing as well as chest compressions. The stricken person made it alive to the EMS vehicle that took nearly 30 minutes to arrive. While I do not know the eventual outcome, I do know he was successfully resuscitated using an Automated External Defibrillator (AED). Furthermore with the quick application of CPR, he likely had a full recovery. Unfortunately, from the crowd response at that time, there were not enough people trained to act in this emergency situation where seconds really count.

Bioengineered Cranial Bones with Multiple Intelligent Functions for the Effective Treatment of Currently Intractable Brain Disorders: Prospects and Challenges

Many neurological and psychiatric disorders with predominantly cerebral cortical pathology, including most severe strokes, traumatic brain injuries, malignant brain tumors, intractable focal epilepsies and dementias such as Alzheimer’s disease are currently difficult, if not impossible, to treat. This causes suffering in almost 100 million people worldwide. 

We propose that bioengineered cranial bones with multiple intelligent functions, including site specific Tran’s meningeal drug delivery and neurotoxin drainage with EEG feedback, can provide effective treatment of these brain disorders by drug combinations that act on both synapses and genes with concomitant selective drainage of harmful extracellular molecules. After examining and summarizing the rationale and feasibility of this proposal, we suggest novel methods for extending the functions of the involved components including synergies with existing devices and we highlight relevant pre clinical results, discussing medical prospects of this novel neuro therapeutic approach. Finally, we discuss key engineering, scientific, clinical and ethical challenges to introducing bio engineered cranial bones with multiple intelligent functions to the clinic within a decade. 

Preliminary Evaluation of the Effects of Cold Atmospheric Plasma Application Rate on the Proliferation Behavior of Keratinocytes in Vitro Measured Using CK-5, CK-10, CK-14, Ki-67 and p53 Expression

Tissue tolerable plasma has been used in preclinical and more recently in clinical settings for the debridement of dead tissue and the removal of bacterial biofilms. Cold plasma therapy is an emerging field in medical sciences; it is mainly due to the beneficial effects that low temperature plasma has demonstrated: anti-inflammatory, ant tumorigenic and anti-microbial effects. 

The advantage of cold plasma therapy over conventional thermal plasma treatments, arc coagulators and desiccators, is that it allows for more precise application and therefore more controllable effects on the tissue. Additionally, cold plasma treatment showed stimulatory effects on wound healing and tissue regeneration. Experiments show that cold atmospheric plasma treatment allows for efficient, non-contact, painless, and antiseptic effects without damaging healthy tissue. As a result of the better understanding of complex plasma phenomena and the development of new plasma sources in the past few years, plasma medicine has developed into an innovative and promising field of research.

Analytic Formulas for the Clinical Issues of a UV-Light-Activated Corneal Crosslinking Device

Modeling the critical issues of the dynamics of UV-light-initiated crosslinking of corneal collagen including the new safety criteria, crosslinking time and the efficacy. A coupled dynamic equations is numerically solved and analytic formulas are derived for three critical parameters: the safety dose (E*), the cross linking time (T*) and the efficacy defined by the increase of corneal stiffness (S). The critical issues of corneal crosslinking is explored by nine parameters: the three extinction coefficients, concentration and diffusion depth of the riboflavin solution, the UV light dose, irradiation duration, the cytotoxic energy threshold of endothelial cells and the corneal thickness.

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New Insights on the Cardiovascular Inflammation due to Multi Layered Plaque Accumulation

Cellular functions such as the maintenance of homoeostasis are regulated by shear forces sensed by endothelial cells. The endothelial cells sense local changes by absorbing the stress and produces signals that either transduce chemical responses or transmit the same to regulate the cellular activity. Certain parts of our body are prone to plaque phenotype and they rupture due to plaque accumulation. The blood cells that are smaller in size under the normal conditions grow in size to block the blood flow through the arteries. Severe stenosis and the local particle concentration leads to high cardio vascular inflammation.

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Solid-phase Immuno Radio Metric Assay (IRMA) of 25-hydroxy Vitamin D and Displacement from Serum Binding Proteins for Resource-limited Settings

The development of a solid-phase immune radiometric assay to satisfy the pressing need for a simple yet effective method for measuring 25-hydroxyvitamin D[25(OH)D] in a serum and thus more suited to routine use in clinical biochemical laboratories. The aim of this study was not to compare our home made with commercially available method but tested for general assay performance, including homemade polyclonal antibody specificity. Methods: We used our home made radioiodine (125I)-based IRMA kit for the detection of 25(OH)D. 

It is based upon, non-competitive displacement agents which enable effective separation of vitamin D metabolites from binding proteins to enable the amount of vitamin D metabolites to be measured, without competing with the proteins or requiring its solvent extraction from the serum.Our package called: “cgea 25(OH)D-irma” is analytically, all qualities we expect from a good medical test kit, with a precision of coefficients below 13%as well as intra-series that in inter-series and inter-batch accuracy with a linearity estimated at 0.8ng/ml and good stability of the radio labeled trace(60 days). Conclusion: Simplification of the methods for extraction and separation has been a key feature in the improvement of assays for vitamin D in Democratic Republic of Congo. 

Old Wine in a New Bottle: Harnessing the Therapeutic Properties of Emodin Derivatives

Studies involving mechanism of emodin, an herbal extract, has revealed its potential as anti-inflammatory, antioxidant and anti-cancer agent. Emodin has been shown to successfully induce apoptosis, down-regulate cancer inducing genes, proving it to be a therapeutically significant pharmacophore. 

Modification of emodin and synthesis of various derivatives have successfully increased efficacy of the molecule in regulating various cellular pathway like MAPK signaling pathway, NF-κβsignaling pathway, ROS mediated pathways and apoptotic pathways. With the advent of various, anti-bacterial properties of emodin may come in rescue to combat emerging drug resistant microbial and parasitic strains. Different emodin derivatives, including the recently reported haloemodin, which inhibits bacterial topoisomerases, can be designed to generate future drugs against resistant pathogens. 

Linear Quadratic Tracking Control of Smooth Pursuit Eye Movements

Conventional feedback control models of the oculo motor system fail to account for the destabilizing effects of neural transmission delays. To address this short coming, a linear quadratic tracking algorithm used to control smoothly pursuing eye movements of various target trajectories is presented. 

Based on the type of input to the system, itis shown that stability, in the presence of large motor feedback delays, can be maintained by modulating weighting factors intrinsic to the model. Conditions, such as the initial orientation of the eye relative to the location of where a target first becomes salient and the possible oscillatory nature that the reference trajectory may present, play important roles in determining the optimal cost to go motor control strategy at the onset of a tracking movement.

Multi-layered Non-Newtonian Plaque Formation causes Inflammation and Cardiovascular Diseases

Heart is a sensitive organ prone to vulnerabilities like plaque phenotype, leading to increased rupture. Blood particles get concentrated as a result of such stress in the blood circulation and distribution. Endothelial cells that are crucial for the maintenance of Cellular functions like homoeostasis are able to sense the changes in its surroundings and induce chemical responses. It may transmit the stress to regulate the cellular activity, leading to concentration of cells and inflammation and cardio-vascular diseases.   

A Multiscale Haemorheological Computer-Based Model of Atherosclerosis: An In-Depth Investigation of Erythrocytes-Driven Flow Characteristics in Atheroma Development

The mortality caused by cardiovascular diseases is dramatically increasing. Atherosclerosis is among the main contributors to this extremely high cardiovascular disease mortality. Atherosclerosis is controlled by mechanical forces exerted by the flow of blood on the inner lining of arteries, the endothelium. 

In order to fight this lethal disease a realistic computational model is required that offers an accurate understanding of the effect of blood flow on the arterial wall. In order to realistically describe complex blood flow patterns and their interaction with the arterial wall, we have developed an integrated computational technique that takes into account both the particulate cellular composition of the blood and the interactions between the particulate blood and the vessel wall, in macro-circulation.

Preface or the Truth Revealed

The truth revealed was when a young man, Nick Kostovic, made public his findings about the power of the Universe, the achieved knowledge he performs in the healing systems of our days. Doctors, patients, and common people thought of him as a magician who penetrated from the clouds to announce a new truth. And this is what it was-a new truth. 

The community of coastal Los Angeles became stunned when terminally sick people began to feel better, when invalids began to walk, when memories returned to Parkinson’s and Alzheimer’s-diseased patients. For the past thirty years, Kostovic has conducted research on the effects of neurological disorders on human beings and spent the last fifteen years working on several projects in connection with bioenergetic physical therapy. 

A Multi-Layer Non-Newtonian Model of Cardiovascular Inflammation

We found that such locations are correlated to the vulnerable plaque phenotype, which is prone to rupture. Our results demonstrate that at locations of high particle concentration, blood particles change the shear stress distribution and magnitude. 

Therefore, the non-Newtonian blood flow assumption provides new insights in the characterisation of plaque built up. These results are combined to in-vitro experiments that suggest the influence of blood particles in the activity of cytokines. An unbalance in pro and anti-inflammatory cytokines has been associated to an increase in inflammation and, consequently, in the volume of plaques forming.

The Standing Acoustic Wave Principle within the Frequency Analysis of Acoustic Signals in the Cochlea

The frequency analysis of auditory perceptions takes place in the cochlea of the inner ear. The cochlea’s task is to transform the entrance vibrations of the oval window into individual frequency components of the acoustic signal entering the outer ear. This frequency analysis is provided by a coupling between the overall acoustic wave in the perilymph and the vibrations of the basilar membrane. 

With regard to the analyzed transformation of signals, the scala vestibuli, scale tympani, basilar membrane and organ of Corti are of the highest importance, the latter of which transforms deformations of the basilar membrane into tension pulses that are further conveyed to the relevant part of the brain. The cavities of the scala vestibuli and scale tympani are filled with the same liquid-perilymph. They are interconnected with a narrow opening called the helicotrema.