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Diabetic Ketoacidosis - What is Diabetic Ketoacidosis?Diabetic ketoacidosis (DKA) is a potentially life-threatening complication in patients with diabetes mellitus. Doctors usually arrive at diagnoses and treatments using an amorphous thought process that lacks structure, and is based largely on pattern recognition and past clinical experience. Psychological studies of scientists demonstrate strong evidence of cognitive limitations that lead to frequent judgment error and a very limited ability to deal with complex information. A new range of treatment is being proffered to the dental profession – treatment of benign non-apneic snoring. A further problem unique to snoring is that the snorer is usually unaware of the problem, and the initial complaint is that of the bed partner or listener of the snoring. Any membraneous part of the upper airway from the nose to the epiglottis that lacks cartilaginous or bony support may vibrate.
The health consequences of snoring range from none (benign clinical sign) to severe sleep disturbance with morbid consequences, in patients with obstructive sleep apnea. Hoffstein regards an AHI<10 in the absence of OSA symptoms such as nocturnal cessation of breathing or awakenings with gasping or choking as the cut-off defining non-apneic, benign snoring. Dentists are given courses in dental school on respiratory physiology, oral anatomy, swallowing, tongue function, orthopedic repositioning of the jaws, and oral prosthetics. Dentists make oral appliances as a result of their professional training and the scope of their license. Dentists are not trained to treat or deal with the morbid medical consequences of OSA such as heart attack, stroke, diabetes, cognitive dysfunction and depression. In oral appliance therapy for snoring and sleep apnea, a reliable ambulatory testing device to establish baseline OSA levels and evaluating treatment outcome is an essential requirement.
One such device is the Braebon Medibyte, an FDA approved miniature 12 channel Class 2 ambulatory polysomnographic recorder. The software allows the doctor to evaluate the entire study, rescore any events or accept the computer interpretation. Treatment results of oral appliances on benign non-apneic snoring can be objectively measured. On the flow sheet for diagnosis and treatment of benign non-apneic snoring we should logically be able to say that treatment outcome is either unsuccessful, is a qualified success or successful. There are numerous possible criteria for evaluation of successful treatment of benign non-apneic snoring. In an ideal world the subjective criteria could be scored on a visual analog scale (VAS), graded 1 – 5.
Should research scientists devise a study to test the minimum snore loudness in decibels that cause arousals in a population of snorers? There is no convincing evidence that benign non-apneic snoring will predictably advance to morbid health consequences as a continuum in the progression of OSA. What are the potential uses of human stem cells and the obstacles that must be overcome before these potential uses will be realized? In the 1960s, scientists who were studying rats discovered two regions of the brain that contained dividing cells that ultimately become nerve cells.
Adult stem cells have been identified in many organs and tissues, including brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium, and testis.
Typically, there is a very small number of stem cells in each tissue and, once removed from the body, their capacity to divide is limited, making generation of large quantities of stem cells difficult. Importantly, scientists must demonstrate that a single adult stem cell can generate a line of genetically identical cells that then gives rise to all the appropriate differentiated cell types of the tissue. As indicated above, scientists have reported that adult stem cells occur in many tissues and that they enter normal differentiation pathways to form the specialized cell types of the tissue in which they reside. Hematopoietic stem cells give rise to all the types of blood cells: red blood cells, B lymphocytes, T lymphocytes, natural killer cells, neutrophils, basophils, eosinophils, monocytes, and macrophages. Epithelial stem cells in the lining of the digestive tract occur in deep crypts and give rise to several cell types: absorptive cells, goblet cells, Paneth cells, and enteroendocrine cells.
Skin stem cells occur in the basal layer of the epidermis and at the base of hair follicles. Although isolated instances of transdifferentiation have been observed in some vertebrate species, whether this phenomenon actually occurs in humans is under debate by the scientific community. In a variation of transdifferentiation experiments, scientists have recently demonstrated that certain adult cell types can be "reprogrammed" into other cell types in vivo using a well-controlled process of genetic modification (see Section VI for a discussion of the principles of reprogramming). In addition to reprogramming cells to become a specific cell type, it is now possible to reprogram adult somatic cells to become like embryonic stem cells (induced pluripotent stem cells, iPSCs) through the introduction of embryonic genes.
How do adult stem cells evolve during development and how are they maintained in the adult? Why do stem cells remain in an undifferentiated state when all the cells around them have differentiated? Do adult stem cells have the capacity to transdifferentiate, and is it possible to control this process to improve its reliability and efficiency? If the beneficial effect of adult stem cell transplantation is a trophic effect, what are the mechanisms?
What are the factors that stimulate stem cells to relocate to sites of injury or damage, and how can this process be enhanced for better healing? Clinical decision-making arrived at by a progression of well- reasoned steps may take more time, but arrives at more logical conclusions and is easier to teach as a new discipline to students who have little or no experience.
When making clinical decisions, doctors’ brains have a very limited ability to manipulate more than four to five variables.
A flow chart creates a framework for conceptualization of the problem and reliable stations for sequential decisions in a logical progression.
All people during sleep have increased inspiratory suction pressure, fast turbulent airflow, increased palatal resistance, negative inspiratory suction and prolonged inspiratory time. Everyone seems to know a snore when they hear one, but as of August 2008 no gold standard definition of a snore by objective measurement has been developed. In terms of signal analysis, interpretation, unique vocal tract characteristics and ideal receiver placement have presented daunting obstacles.
Examples of such structures with vibrating potential are swollen nasal membranes, soft palate, faucial pillars, pharyngeal walls, tonsils, adenoids, uvula and tongue.

While snoring usually accompanies OSA, snoring by itself provides a very low diagnostic predictability for OSA. No studies have implicated benign non-apneic snoring as being an increased risk factor for hypertension, vascular disease, heart attack or stroke. Dental education teaches about the morbidity and consequences of OSA, diabetes, depression, and obesity.
It records snores in decibels and allows the user to click and listen to any snore or series of snores desired. A second recording is done two to three weeks following delivery and fitting of the oral appliance, when the patient has had sufficient time to adjust to wearing their intraoral device. Frequency of snores, loudness of the loudest snores, average loudness of snores, and number of snores per hour can all be measured. Numeric values of 1 – 5 could also be assigned for the scoring of objective criteria and a scale devised such as the Epworth Sleepiness Scale. The primary roles of adult stem cells in a living organism are to maintain and repair the tissue in which they are found.
Scientists have found adult stem cells in many more tissues than they once thought possible. In the 1950s, researchers discovered that the bone marrow contains at least two kinds of stem cells. Despite these reports, most scientists believed that the adult brain could not generate new nerve cells.
Scientists in many laboratories are trying to find better ways to grow large quantities of adult stem cells in cell culture and to manipulate them to generate specific cell types so they can be used to treat injury or disease. In a living animal, adult stem cells are available to divide for a long period, when needed, and can give rise to mature cell types that have characteristic shapes and specialized structures and functions of a particular tissue. Those from bone marrow (bone marrow stromal stem cells, skeletal stem cells) give rise to a variety of cell types: bone cells (osteoblasts and osteocytes), cartilage cells (chondrocytes), fat cells (adipocytes), and stromal cells that support blood formation.
The epidermal stem cells give rise to keratinocytes, which migrate to the surface of the skin and form a protective layer.
Instead of transdifferentiation, the observed instances may involve fusion of a donor cell with a recipient cell. This strategy may offer a way to reprogram available cells into other cell types that have been lost or damaged due to disease. Thus, a source of cells can be generated that are specific to the donor, thereby increasing the chance of compatibility if such cells were to be used for tissue regeneration.
Is donor cell-recipient cell contact required, secretion of factors by the donor cell, or both? Strategies for chunking, organizing and prioritizing information also help sharpen doctors’ reasoning skills. Crude non-optimized flow charts have repeatedly been shown to be more reliable than subjective human judgment.
The pathogenesis of snoring is vibrating tissues accompanied by increased collapsibility and incomplete pharyngeal obstruction or narrowing of the pharyngeal airway. According to Victor Hoffstein, renowned author of several seminal treatises on snoring, there are no studies validating the electronic measurement of a sound scored as a snore by a PSG technician, by a computer or its perception as a snore by listeners. When both are measured simultaneously during sleep, no consistent temporal correlation is found between nasal resistance and snoring. In a study of a group of patients who snored, suspected of having OSAand tested with polysomnography, more than 50% had an AHI less than 10. Repeated studies have failed to support an association between benign non-apneic snoring and decreased daytime cognitive function.
Dental students are schooled in taking a good medical history and understanding the significance of their findings. Oral appliances for benign non-apneic snoring are the least invasive, highest compliance and most comfortable of the effective treatments available. The Medibyte is unique among ambulatory PSG units in that it records snoring at a high enough sampling rate to allow spectral analysis of the snore sound from 0 – 1000 Hz. The problem of patients with benign non-apneic snoring may not be the effect of snoring and the appliance on them but on their sleep partner.
Criteria and standards based on physiologic validation obtained by objective measurement is an ideal. It is the opinion of this clinician that a scale is not appropriate for evaluation of therapy for snoring. An average score on such an objective study would not be representative of a successful treatment standard for many snorers. Scientists also use the term somatic stem cell instead of adult stem cell, where somatic refers to cells of the body (not the germ cells, sperm or eggs). This finding has led researchers and clinicians to ask whether adult stem cells could be used for transplants. One population, called hematopoietic stem cells, forms all the types of blood cells in the body. It was not until the 1990s that scientists agreed that the adult brain does contain stem cells that are able to generate the brain's three major cell types—astrocytes and oligodendrocytes, which are non-neuronal cells, and neurons, or nerve cells. In many tissues, current evidence suggests that some types of stem cells are pericytes, cells that compose the outermost layer of small blood vessels. Some examples of potential treatments include regenerating bone using cells derived from bone marrow stroma, developing insulin-producing cells for type 1 diabetes, and repairing damaged heart muscle following a heart attack with cardiac muscle cells.
The following are examples of differentiation pathways of adult stem cells (Figure 2) that have been demonstrated in vitro or in vivo.
However, it is not yet clear how similar or dissimilar mesenchymal cells derived from non-bone marrow sources are to those from bone marrow stroma.
Another possibility is that transplanted stem cells are secreting factors that encourage the recipient's own stem cells to begin the repair process. For example, one recent experiment shows how pancreatic beta cells, the insulin-producing cells that are lost or damaged in diabetes, could possibly be created by reprogramming other pancreatic cells.
However, like embryonic stem cells, determination of the methods by which iPSCs can be completely and reproducibly committed to appropriate cell lineages is still under investigation.

The three necessary conditions for snoring are vibrating tissue, flow limitation and sleep. The relevant physiological parameters in snorers compared to non-snorers are upper airway diameter, cross sectional area of the pharynx, pharyngeal shape, pharyngeal collapsibility, nasal and pharyngeal resistance to airflow. Snoring, taken alone as a symptom, has a very low diagnostic accuracy to predict sleep apnea.
Also significant is the fact that benign non-apneic snoring does not have anywhere near the morbidity of OSA.
Reduction of frequency and loudness of snores may not be as meaningful as the sensitivity of the sleep partner. In sleep medicine many definitions are arbitrarily set and not based on scientifically validated parameters.
The state of sleep science is such that snoring is too heterogeneous a problem for a single number to represent all the factors necessary to determine success at treatment of snoring. Also the study would have to be repeated on the sleep partners of the snorers because it is often their arousal level that determines both the need for therapy and the measure of success of the snoring therapy. Success of treatment is mutually agreed upon on an individual case basis by clinician and patient, and in many cases the sleep partner. Unlike embryonic stem cells, which are defined by their origin (cells from the preimplantation-stage embryo), the origin of adult stem cells in some mature tissues is still under investigation.
In fact, adult hematopoietic, or blood-forming, stem cells from bone marrow have been used in transplants for more than 40 years. A second population, called bone marrow stromal stem cells (also called mesenchymal stem cells, or skeletal stem cells by some), were discovered a few years later. Stem cells may remain quiescent (non-dividing) for long periods of time until they are activated by a normal need for more cells to maintain tissues, or by disease or tissue injury. Even when transdifferentiation has been detected, only a very small percentage of cells undergo the process.
By "re-starting" expression of three critical beta cell genes in differentiated adult pancreatic exocrine cells, researchers were able to create beta cell-like cells that can secrete insulin. It has been attributed to sleep fragmentation, as a result of snoring arousals, but the arousal frequency did not correlate to amplitude or frequency of snores.
They are already looking at the same anatomic structures used to determine a referral for diagnosis of OSA and signs that suggest a patient may be snoring. The cost of the Medibyte is very reasonable, the cost per study for expendables is cheap and the reliability is excellent. There is an ongoing debate in the sleep community whether snoring is under central control or peripheral mediation by anatomic characteristics.
Dentists having the correct measurement devices and training are logical health care specialists for diagnosis and treatment of benign non-apneic snoring.
Scientists now have evidence that stem cells exist in the brain and the heart, two locations where adult stem cells were not at first expected to reside.
These non-hematopoietic stem cells make up a small proportion of the stromal cell population in the bone marrow and can generate bone, cartilage, and fat cells that support the formation of blood and fibrous connective tissue.
Snoring can occur during exclusive nasal breathing, exclusive oral breathing or combined oronasal breathing. Objective measurement tools to localize the originating site of snores have not been devised.
Further, they are examining these characteristics based on a higher level of formal training than most physicians receive in this area.
The data is presented in a language that facilitates excellent communication and reports to referring doctors.
The parameters defining mild, moderate and severe obstructive sleep apnea are arbitrarily set. Snoring is a complex multifactorial problem whose etiology may vary from patient to patient. The uniqueness of each patient’s physiological and anatomic characteristics, the limitations of scientific knowledge of snoring and the limitations of each available therapy must be appreciated in determining clinical success. Trial and error, patience by the clinician and patient and confidence in the relationship are all variables determining satisfaction.
Following this protocol, dentists involved in the diagnosis and treatment of benign non-apneic snoring should also be the best resource for referral of OSA patients to sleep specialists. If the differentiation of adult stem cells can be controlled in the laboratory, these cells may become the basis of transplantation-based therapies.
While not transdifferentiation by definition, this method for reprogramming adult cells may be used as a model for directly reprogramming other adult cell types. It is logical and sensible that dentistry as a profession should be among the very best screeners and referrers of OSA patients to sleep specialists. It allows a clinician to practice at the state of the science and retest patients as frequently as needed to get it right. Research criteria for success of oral appliance therapy for OSA, 50% reduction of AHI, AHI below 10, or both, are arbitrary. It is not like dentistry does not know much about snoring – current medical science does not know any more.
Rejection of payment for UARS by insurance companies and rejection of payment for OSA if the AHI is below 10 are arbitrary and not based on any scientific criteria.
Successful treatment using “The Protocol” is based on maximum improvement attainable using an oral appliance. The clinician and patient should be satisfied and agree that all possible alternatives have been tried.

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