The detection of cervical intraepithelial neoplasia by electrical impedance spectroscopy: The effects of acetic acid and tissue homogeneity

Objective. To evaluate the efficacy of an electrical impedance probe (Epitheliometer) in the diagnosis of high grade cervical intraepithelial neoplasia (CIN) in women referred with cervical smear abnormalities and to assess the effect of acetic acid (AA) and tissue boundaries on the measurements. Methods. A prospective observational study was undertaken in the colposcopy clinic. One hundred and sixty-five women, either with a clinical indication or abnormal cervical cytology, were recruited into the study. A pencil type probe was used to record impedance spectra from 12 points on the cervix before and after the application of 5% AA. Spectra were also recorded from tissue boundaries. Colposcopic examinations, including probe positioning, were video recorded to allow for correlations between histopathological diagnosis of colposcopically directed biopsies, colposcopic impression and the diagnosis based on impedance measurements. Results. Receiver operating characteristic (ROC) curves were derived. The areas under the curves (AUCs) to discriminate original squamous from high grade CIN were 0.80 (pre AA) and 0.79 (post AA). Comparison of these curves showed no significant difference, indicating that application of AA does not produce a large change in spectra. The probe Could distinguish tissue boundaries from homogeneous tissue points. Conclusion. The Epitheliometer has the potential to be used as an adjunct to colposcopy in the diagnosis of high grade CIN. It has the advantage of real time results, decreasing the need for diagnostic cervical biopsies, and facilitates a wider use of the 'see and treat' policy without the risk of overtreatment. (C) 2009 Elsevier Inc. All rights reserved

Subjectivity and inadvertence in computational art: muta-morphosis

Creativity is stochastic and assumptive in nature. The importance of randomness in the creative process must not be ignored, underestimated or intentionally disregarded in a condescending way. Notions of chance, randomness, or unpredictability are much important, especially when it comes to artistic creation. In addition to above notions, serendipity can be seen as the expected contribution for making expedient discoveries by coincidence, by chance. To put serendipity into work, there is need to accumulate a list of questions that need solving, acquaintance with already existing answers, and their use in daily life. Only when this knowledge is present, ‘chance’ can take its part in establishing the perfect milieu for the ‘problem’ and the ‘solution’ to nd each other. If there is already a great deal of knowledge accrued in our minds about the problem and the requisites for the solution, chance adds the nal piece to the puzzle. It is when we can start to talk about a traditional ‘prescriptive, authoritarian and rather conventional’ aesthetics vs. a new ‘generative, irregular, unprescribed’ aesthetics

Barrett's esophagus: natural history

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86834/1/j.1749-6632.2011.06057.x.pd

Aspects on endoscopic characterization and clinical management of Barrett's esophagus

Barrett's esophagus (BE) is considered to result from prolonged gastroesophageal reflux and is the only known precursor of esophageal adenocarcinoma. The clinical management of BE patients aims to control esophageal reflux to reduce mucosal injury and neoplastic progression, and to detect early neoplastic lesions in Barrett’s mucosa, suitable for curative endoscopic treatment. The first part of this thesis evaluates the effect of a stepwise increase in the dose of proton pump inhibitors (PPI), on esophageal acidic reflux, symptoms and histology in long segment BE patients (group 1, n=24). We also compare these outcomes in BE patients under PPI with the results of BE patients after clinically successful fundoplication (group 2, n=30). In all but one patient in group 1, it was possible to normalize acid reflux with PPI, resulting in improvements in symptom scores. However, symptomatic amelioration was only significant in the first step of PPI treatment. Patients with PPI or fundoplication had the same levels of symptom scores. Normalization of the acid reflux in both groups was associated with reductions of papillary length, thickness of the basal cell layers, dilation of intercellular spaces, and acute and chronic inflammation of the squamous epithelium. We did not find a significant change in markers of proliferation and differentiation in Barrett’s mucosa associated with normalization of acid reflux in either group. The second part of this thesis assesses 3 different endoscopic classification systems, Amsterdam, Kansas and Nottingham, developed for the characterization of Barrett’s mucosa. These classifications use magnification endoscopy with narrow band imaging (ME-NBI) for the identification of intestinal metaplasia and dysplasia in Barrett’s mucosa. We used 84 video segments from Barrett’s mucosa, that were randomly selected and blindly evaluated by 9 observers with different expertise in the field. All classifications were feasibly but showed suboptimal accuracy and low inter-observer agreement, with slightly better results for the Amsterdam classification. The last part of this thesis evaluates the role of a structured learning program for the application of the Amsterdam classification system. We used the first 70 videos from the 84 randomly selected videos from the previous study. While, during the learning process, there was a decrease in the time spent for evaluation and an increase in declared certainty of prediction, the accuracy in histological prediction did not improve. This classification system was found to be suboptimal in terms of accuracy and inter- and intra-observer agreements. This thesis shows that, in long segment BE patients, acid reflux and symptom scores correlated through several steps of the PPI treatment process, achieving the same level as after a successful fundoplication. If a single dose of PPI is associated with marked improvement of symptoms, higher doses still may be needed for complete acid suppression. Minor changes were found among morphological markers of reflux disease, both in the glandular and in the squamous epithelium, irrespective of medical or surgical treatment. Our results underscore the questionable utility of ME-NBI classification systems for clinical routine practice in BE

A characterisation of the integumentary skeleton of lizards (Reptilia: Squamata)

Osteoderms (ODs) are present within the dermis of 14 families of squamates although snakes and Sphenodontidae lack ODs. The expression of ODs within squamates has been described as highly variable and diverse since they were first reported. Some examples of squamate OD expression are as compound structures, fused together into overlapping, imbricating plates (as in Scincidae); as distorted, bent cylinders, partially overlapping one another (as in Varanidae), or as discrete, regularly tessellated, non-overlapping, polygonal beads (as in Helodermatidae), but this is not an exhaustive list. Currently, our understanding of OD structure-to-function relationships, general anatomy and internal composition remains limited. In this study, using histological staining, computed tomography, polarised light microscopy and electron microscopy, the microstructure of materials comprising ODs from multiple families of lizards is revealed. The results show that ODs are comprised of different proportions of numerous biomaterials including osteodermine, a highly mineralised, dense capping tissue on the apical surface of the osteoderm; lamellar bone rich in secondary osteons (haversian bone tissue), Sharpey-fibred bone, woven bone and parallel-fibred bone. These results are an indication that ODs of closely related families can differ substantially in terms of their overall anatomy, the structural composition of material elements and consequently their function and ontogeny. Histological variation within the biomineralised tissues is shown to relate to differences in overall OD architecture; these data provide insights into the mechanism of formation of ODs from different families and afford a direct comparison of the histological properties between the ODs of the multiple species. Attempts are made to elucidate the relationship between OD expression and other variables, such as function and phylogeny. Finally, the varied assortment of biomaterials found within ODs manifesting in diverse hierarchical structures are shown to be valuable in future translational applications, including the creation of bioinspired materials

Osteoarthritis of the equine temporomandibular joint

Degeneration of the temporomandibular joint (TMJ) is a well reported condition in several mammalian species, including man. Yet, for the length of time that horses have been domesticated, we understand very little about the conditions affecting their TMJs. Up to this point, equine temporomandibular joint disease (TMJD) has been infrequently reported, with cases occurring secondary to a traumatic event, one that results in overt inflammation, either due to facture, joint sepsis, or both. With various etiologic causes of degenerative joint disease (DJD) in other joints, the apparent absence of these causes within equine TMJD is an enigma. As such, the focus of this work is to characterize the clinical effect of TMJ inflammation on mastication and histologically evaluate the changes seen within equine TMJs as horses age. The first work is a retrospective case report describing the occurrence of bilateral, non- traumatic, DJD in the TMJs, of a geriatric horse. The focus-patient had no history of trauma, but slowly developed signs of headshaking and began suffering from several bouts of impaction colic. When eating, the horse would consistently drop partially chewed feed (quid) and the jaw would make an audible ‘clicking’ sound. Computed tomography of the TMJs demonstrated bilateral mineralization of the rostral aspect of both intra-articular discs. Intraarticular injection of corticosteroid resulted in temporary resolution of the quidding behavior, the ‘clicking’ sound, and the recurrent episodes of colic. The occurrence of bilateral TMJD in an elderly horse, without evidence of trauma or sepsis, is unique. It suggests that, like many other joints, age-related changes occur within the TMJ, predisposing the joint to degeneration. The second study examines the relationship between the onset of acute unilateral inflammation of the TMJ and the development of clinical signs; distortion of the masticatory cycle, effusion of the affected TMJ, and aversion behavior suggestive of pain. Using a three-dimensional (3-D) motion tracking system, the authors examined the masticatory cycle of six horses, free of dental abnormalities. Horses were observed chewing grass hay over three minute intervals. Regardless of the side of mastication, all horses were injected in the left TMJ with lipopolysaccharide. Six hours post-injection the horses were re-assessed. All data were compared using paired t-tests. iii Four of six horses developed effusion of the injected TMJs; two also began quidding. All horses injected on the “chewing side”, switched sides post-injection; the two injected contralateral to the “chewing side” did not. All horses showed reduced vertical pitch of the mandible (mouth opening), but not lateral movement, post-injection. Overall rostrocaudal movement of the mandible did not change, but timing relative to the opening and closing phases of the cycle was different. Although horses demonstrated aversion behavior, all subjects continued to eat. The third, and final, study analyses the histologic presence of age-related change within the TMJs of 11 clinically normal horses. Each TMJ was frozen in-situ and sectioned in 5 mm slices, at random (transverse or sagittal direction). A histologic assessment for age-related change was made using a modified Mankin scoring system. The horses were divided into three age groups. The overall joint score was not significantly different between left and right joints within each age group. As the age of the horses in each group increased, there was a significant increase in the total joint score (accumulation of age-related changes); the youngest group of horses were significantly different than those in the oldest group, but neither were significantly different from the middle- aged group of horses

The relationship between cholesterol crystals, foamy macrophages and haemosiderin in odontogenic cysts

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Integrin-mediated traction force enhances paxillin molecular associations and adhesion dynamics that increase the invasiveness of tumor cells into a three-dimensional extracellular matrix.

Metastasis requires tumor cells to navigate through a stiff stroma and squeeze through confined microenvironments. Whether tumors exploit unique biophysical properties to metastasize remains unclear. Data show that invading mammary tumor cells, when cultured in a stiffened three-dimensional extracellular matrix that recapitulates the primary tumor stroma, adopt a basal-like phenotype. Metastatic tumor cells and basal-like tumor cells exert higher integrin-mediated traction forces at the bulk and molecular levels, consistent with a motor-clutch model in which motors and clutches are both increased. Basal-like nonmalignant mammary epithelial cells also display an altered integrin adhesion molecular organization at the nanoscale and recruit a suite of paxillin-associated proteins implicated in invasion and metastasis. Phosphorylation of paxillin by Src family kinases, which regulates adhesion turnover, is similarly enhanced in the metastatic and basal-like tumor cells, fostered by a stiff matrix, and critical for tumor cell invasion in our assays. Bioinformatics reveals an unappreciated relationship between Src kinases, paxillin, and survival of breast cancer patients. Thus adoption of the basal-like adhesion phenotype may favor the recruitment of molecules that facilitate tumor metastasis to integrin-based adhesions. Analysis of the physical properties of tumor cells and integrin adhesion composition in biopsies may be predictive of patient outcome