Fibromyalgia: A Unifying Neuroendocrinologic Model for Understanding Its Pathophysiology

Fibromyalgia is believed to affect at least 2% of the population. Despite advances in the scientific understanding of the derangements of central and peripheral pain processing mechanisms in fibromyalgia, no current models of its pathophysiology account for the other clinical conditions associated with it such as fatigue, migraine headache, irritable bowel syndrome, and sleep cycle abnormalities. A neuroendocrinologic model of fibromyalgia is presented that accommodates both its known central and peripheral pain mechanisms as well as the myriad of hormonal, visceral, and psychological symptoms associated with that disorder. This model also provides a unifying pathophysiologic basis of fibromyalgia and chronic muscle pain, and offers the potential for developing new avenues of research and treatment for these enigmatic, frequently disabling medical conditions

Extraction and selection of muscle based features for facial expression recognition

In this study we propose a new set of muscle activity based features for facial expression recognition. We extract muscular activities by observing the displacements of facial feature points in an expression video. The facial feature points are initialized on muscular regions of influence in the first frame of the video. These points are tracked through optical flow in sequential frames. Displacements of feature points on the image plane are used to estimate the 3D orientation of a head model and relative displacements of its vertices. We model the human skin as a linear system of equations. The estimated deformation of the wireframe model produces an over-determined system of equations that can be solved under the constraint of the facial anatomy to obtain muscle activation levels. We apply sequential forward feature selection to choose the most descriptive set of muscles for recognition of basic facial expressions.Publisher's VersionAuthor Post Prin

Co-occurrence of amyotrophic lateral sclerosis and Leber's hereditary optic neuropathy: is mitochondrial dysfunction a modifier?

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DETERMINATION OF THE EXTRAVASCULAR BURDEN OF CARBON MONOXIDE (CO) ON HUMAN HEART

Noninvasive measurements of myocardial carboxymyoglobin levels (%MbCO) and oxygen tensions (PtO2) are difficult to obtain experimentally. We have developed a compartmental model which allows prediction of myocardial %MbCO levels and PtO2 for varied carbon monoxide (CO) exposures. The cardiac compartment in the model consists of vascular subcompartments which contain two tissue subcompartments varying in capillary density. Mass-balance equations for oxygen (O2) and CO are applied for all compartments. Myocardial oxygen consumption and blood flow are quantified from predictive formulas based on heart rate. Model predictions are validated with experimental data at normoxia, hypoxia, exercise and hyperoxia. CO exposures of varying concentration and time (short-high, long-low), CO rebreathing during 100% O2, and exposure during exercise is simulated. Results of the simulations demonstrate that during CO exposures and subsequent therapies, the temporal changes of %MbCO in the heart differ from those of carboxyhemoglobin levels (%HbCO). Analysis of correlation between %HbCO, %MbCO and PtO2 was done to understand myocardial injury due to CO hypoxia. This thesis demonstrates that the model is able to anticipate the uptake and distribution of CO in the human myocardium and thus can be used to estimate the extravascular burden (MbCO, PtO2 ) of CO on the human heart

Label-free Raman spectroscopic imaging to extract morphological and chemical information from a formalin-fixed, paraffin-embedded rat colon tissue section.

Animal models and archived human biobank tissues are useful resources for research in disease development, diagnostics and therapeutics. For the preservation of microscopic anatomical features and to facilitate long-term storage, a majority of tissue samples are denatured by the chemical treatments required for fixation, paraffin embedding and subsequent deparaffinization. These aggressive chemical processes are thought to modify the biochemical composition of the sample and potentially compromise reliable spectroscopic examination useful for the diagnosis or biomarking. As a result, spectroscopy is often conducted on fresh/frozen samples. In this study, we provide an extensive characterization of the biochemical signals remaining in processed samples (formalin fixation and paraffin embedding, FFPE) and especially those originating from the anatomical layers of a healthy rat colon. The application of chemometric analytical methods (unsupervised and supervised) was shown to eliminate the need for tissue staining and easily revealed microscopic features consistent with goblet cells and the dense populations of cells within the mucosa, principally via strong nucleic acid signals. We were also able to identify the collagenous submucosa- and serosa- as well as the muscle-associated signals from the muscular regions and blood vessels. Applying linear regression analysis to the data, we were able to corroborate this initial assignment of cell and tissue types by confirming the biological origin of each layer by reference to a subset of authentic biomolecular standards. Our results demonstrate the potential of using label-free Raman microspectroscopy to obtain superior imaging contrast in FFPE sections when compared directly to conventional haematoxylin and eosin (H&E) staining

From Falx to Fingertips: An Exercise in Mind-Body Awareness Through Acupuncture

This is a subjective account of an acupuncture treatment that includes a brief scientific exploration of its mechanisms of action. Additionally, connections are made between acupuncture and osteopathic manual manipulation, yoga, and meditation

Doctor of Philosophy

dissertationThe mammalian diaphragm is the most critical skeletal muscle and defects in the development of the diaphragm give rise to congenital diaphragmatic hernias (CDH), which are common and frequently lethal birth defects. The diaphragm has been proposed to develop from multiple embryonic sources, but how these sources are integrated to form the diaphragm and how defects in diaphragm development induce CDH is poorly understood. Using mouse genetics we demonstrate that the pleuroperitoneal folds (PPF), transient developmental structures, will give rise to connective tissue fibroblasts throughout the diaphragm. Furthermore, we show that the PPFs non-cell autonomously regulate the somitically-derived muscle of the diaphragm and control the morphogenesis of the diaphragm. Deletion of candidate CDH genes, Gata4 and Porcn, specifically within the PPF generates CDH with 100% penetrance, demonstrating that the PPFs are the cellular source of CDH defects. Deletion of Gata4 in the PPF causes early defects in muscle progenitor number and localization, creating amuscularized regions that will form CDHs. Interestingly, PPF-specific deletion of Porcn, which is required for secretion of Wnt ligand, produces late defects in diaphragm development and prevents the diaphragm muscle from spreading completely to the most ventral region of the diaphragm. This demonstrates that Wnt signals from the PPF are critical for the formation of the ventral muscle of the diaphragm. Furthermore, we propose that signals from the PPF may be critical for inducing muscle precursors to migrate from the somites to the diaphragm and acquisition of these signals may have allowed evolution of the muscularized mammalian diaphragm. This work demonstrates the essential roles of the PPF-derived connective tissue fibroblasts in all steps of diaphragm development