Diss. Umeå : Univ., 2004.

No description available.

This thesis presents data on two separate areas relevant to the prevention of HIV and sexually transmitted infection (STI) transmission in homosexual men. These data arise from the community-based Health in Men (HIM) cohort of HIV-negative homosexual men in Sydney. First, the association of circumcision status with HIV and STIs was examined. Older age, ethnicity and country of birth were demographic factors independently associated with circumcision status. Self-report was a valid measure of circumcision status in this population. Overall, being circumcised was associated with a non-significant reduced risk of HIV seroconversion in the HIM cohort (HR 0.76, 95% CI 0.41-1.41, p=0.381). Among the one-third of participants predominantly practising the insertive role in anal intercourse (AI), being circumcised was associated with a significantly reduced risk of HIV infection (HR 0.15, 95% CI 0.03-0.80, p=0.026). Circumcised HIM participants also had a lower risk of incident syphilis (HR 0.35, 95% CI 0.15-0.84, p=0.019), however circumcision status had no significant effect on the remainder of prevalent and incident STIs examined. Second, risk factors for pharyngeal gonorrhoea and chlamydia were investigated. The BD ProbeTec nucleic acid amplification test (NAAT) had a positive predictive value (PPV) for pharyngeal gonorrhoea diagnosis of only 30.4% (95% CI 25.2-36.1%) when compared to a previously validated NAAT targeting the gonococcal porA pseudogene. Pharyngeal gonorrhoea was common in HIM, mostly occurred without concurrent anogenital infection and may frequently spontaneously resolve. Infection was independently associated with younger age (p-trend=0.001), higher number of male partners (p-trend=0.002), contact with gonorrhoea (p<0.001) and insertive oro-anal sex with casual partners (p-trend=0.044). Pharyngeal chlamydia was less common but a high prevalence/incidence ratio suggested that infection may persist in the pharynx for long periods. Pharyngeal chlamydia was independently associated with receptive penile-oral sex with casual partners (p-trend=0.009). In conclusion, circumcision may have a role as an HIV prevention intervention among the subgroup of homosexual men who predominantly practise insertive rather than receptive AI. Regular screening of the pharynx including a validated supplemental NAAT for gonorrhoea diagnosis may prevent much transmission to anogenital sites, whereas chlamydia occurs too infrequently in the pharynx to recommend routine screening in homosexual men.

Low resolution pharyngeal manometry is an invasive diagnostic method that has recently been used as a biofeedback device for swallowing rehabilitation. The University of Canterbury Rose Centre uses pharyngeal manometry to diagnose and rehabilitate subjects who suffer from pharyngeal mis-sequencing. Pharyngeal mis-sequencing occurs when pressure is applied simultaneously throughout the pharynx rather than sequentially. Rehabilitation can only be performed in clinic due to the need for specialized equipment and trained staff, and the invasiveness of the test limits the time that can be spent training. As an alternative method to measure the pharyngeal pressure sequence, bioimpedance has been investigated by a previous University of Canterbury Master’s student. A prototype was developed that measured bioimpedance in two locations as a proxy for pharyngeal pressure sequence. The prototype device named GULPS (Guided Utility for Latency in Pharyngeal Swallowing), measured a change in impedance during swallowing. However, the features of this waveform were inconsistent and were not present during every swallow. The frequency of the current that passes through tissue affects its path through the tissue, therefore impacting the measured impedance. To improve the consistency of the impedance measurement, the effect of current injection frequency was investigated. A modular-hardware system was created from the original design to allow testing of different injection frequencies. The hardware was further developed by replacing the method of generating the constant amplitude current injection signal. The improvement to the design resulted in a differently-shaped waveform to that of the previous prototype, including a new feature. This feature is a single peak that occurred in both channels and was reproduced in every swallow. Experimentation showed that the features were not obviously frequency dependent. The separation between the peaks of the two impedance channels was compared with the separation between the two pressure peaks recorded during simultaneous pharyngeal manometry but there was no significant correlation between the two measures of peak-peak separations. Two alternative hardware/signal conditioning changes were trialled: electrical isolation of each channel and a subtraction method, which aims to remove the effect of the changing impedance between the two electrode channels. Electrical isolation of the two channels had no effect on the impedance waveforms. However, the subtraction method produced a different output and requires further investigation as the output was inconsistent. Bluetooth communication was integrated into the GULPS hardware, and a corresponding Android Application (App) was written. The developed App was successful in displaying the impedance measurement output and adds greater user flexibility, allowing the user to interface with the bioimpedance measurement hardware from their tablet or phone. With no measured significant correlation between GULPS and pharyngeal manometry, further research needs to be performed to better relate the features measured by GULPS to those seen during pharyngeal manometry. Until this can be achieved, the GULPS device cannot replace pharyngeal manometry for biofeedback-based rehabilitation of pharyngeal mis-sequencing.

This thesis presents data on two separate areas relevant to the prevention of HIV and sexually transmitted infection (STI) transmission in homosexual men. These data arise from the community-based Health in Men (HIM) cohort of HIV-negative homosexual men in Sydney. First, the association of circumcision status with HIV and STIs was examined. Older age, ethnicity and country of birth were demographic factors independently associated with circumcision status. Self-report was a valid measure of circumcision status in this population. Overall, being circumcised was associated with a non-significant reduced risk of HIV seroconversion in the HIM cohort (HR 0.76, 95% CI 0.41-1.41, p=0.381). Among the one-third of participants predominantly practising the insertive role in anal intercourse (AI), being circumcised was associated with a significantly reduced risk of HIV infection (HR 0.15, 95% CI 0.03-0.80, p=0.026). Circumcised HIM participants also had a lower risk of incident syphilis (HR 0.35, 95% CI 0.15-0.84, p=0.019), however circumcision status had no significant effect on the remainder of prevalent and incident STIs examined. Second, risk factors for pharyngeal gonorrhoea and chlamydia were investigated. The BD ProbeTec nucleic acid amplification test (NAAT) had a positive predictive value (PPV) for pharyngeal gonorrhoea diagnosis of only 30.4% (95% CI 25.2-36.1%) when compared to a previously validated NAAT targeting the gonococcal porA pseudogene. Pharyngeal gonorrhoea was common in HIM, mostly occurred without concurrent anogenital infection and may frequently spontaneously resolve. Infection was independently associated with younger age (p-trend=0.001), higher number of male partners (p-trend=0.002), contact with gonorrhoea (p<0.001) and insertive oro-anal sex with casual partners (p-trend=0.044). Pharyngeal chlamydia was less common but a high prevalence/incidence ratio suggested that infection may persist in the pharynx for long periods. Pharyngeal chlamydia was independently associated with receptive penile-oral sex with casual partners (p-trend=0.009). In conclusion, circumcision may have a role as an HIV prevention intervention among the subgroup of homosexual men who predominantly practise insertive rather than receptive AI. Regular screening of the pharynx including a validated supplemental NAAT for gonorrhoea diagnosis may prevent much transmission to anogenital sites, whereas chlamydia occurs too infrequently in the pharynx to recommend routine screening in homosexual men.

The pharyngeal foregut endoderm (PFE) gives rise to several important organs including the thyroid, thymus and parathyroid glands. In mice and humans, defects in the development of PFE can lead to thymic aplasia and aberrations in thymic epithelial cell (TEC) function can lead to immunodeficiency or autoimmune disease. Successful differentiation of pluripotent stem cells (PSCs) to PFE could provide a renewable cell source that enables the study of human diseases that originate in the PFE. Here, I identify signaling pathways that influence the differentiation of PSCs to PFE. Firstly, using a novel mouse reporter PSC line we develop a protocol that generates a Pax9 expressing population that is enriched for PFE markers and upon transplantation can form organized epithelial structures. However, since this protocol was inefficient for human PSCs, we subsequently identified additional signaling pathways required for the efficient generation of human PFE and determined a key role for retinoic acid. Upon transplantation, the human PFE gives rise to TECs, a ventral PFE derivative. Finally, to facilitate future investigation into the gene regulatory networks in PFE, we develop a CRISPR-effector system to modulate endogenous gene expression in PSCs. We demonstrate that developmentally relevant genes can be repressed or induced, thereby influencing the cellular state. These data present strategies to generate cells of the PFE lineage from PSCs, facilitating the production of cells for patient-specific disease modeling or cell replacement therapies, and a method to interrogate gene and regulatory element function in PFE and its derivatives.

In view of the paucity of detailed information in the literature relevant to the upper digestive tract of the Nile crocodile, this study describes the morphological and histological features of the oral cavity (gingivae, palate and tongue), pharyngeal cavity and oesophagus of the Nile crocodile, Crocodylus niloticus (Laurenti, 1768) using light microscopy. The findings, which were supplemented by scanning electron microscopy, were compared with published information. The ciliated component of the oesophagus was also examined using transmission electron microscopy. The oral cavity had the form of a triangle and was dorso-ventrally flattened. The dorsal limit was formed by the palate and the ventral limit by the broad-based tongue. The close proximity of the tongue and palate severely limited the space within the cavity. The caudal border of the cavity was formed by the dorsal and ventral components of the gular valve. The epithelium of the palate, gingivae and tongue was stratified squamous in nature and appeared lightly keratinised. Specialised epithelial structures in the palate, gingivae and tongue, revealed by both light microscopy (LM) and scanning electron microscopy (SEM), bore characteristics resembling structures responsible for pressure and taste reception. Glandular tissue in the tongue was arranged in a triangular formation in the posterior region and displayed morphological features ascribed to salt secreting glands described in other Crocodilia. There were no palatine glands in the oral region of the palate, except that the oral surface of the dorsal gular fold contained branched tubular mucus secreting glands. The pharyngeal cavity was also dorso-ventrally flattened and was bordered rostrally by the flaccid dorsal gular fold, which displayed a median apical notch, and the ventral gular fold, which was supported internally by the broad rostral tip of the basihyal plate (hyaline cartilage). In the occluded mouth, the dorsal gular fold and the more rostrally positioned ventral component of the gular valve isolated the pharyngeal cavity. This arrangement is essential in preventing the crocodile from drowning (flooding of the pharyngeal cavity) while capturing prey. The roof of the pharyngeal cavity was characterised by the opening to the internal nares (an extension of the nasal passage from the external nares), the fibrous Eustachian plug sealing the common opening to the paired Eustachian ducts and a nodular tonsillar region, which was situated caudo-laterally to the Eustachian plug. Throughout this region, the epithelium was typically ciliated with goblet cells. However, the tonsillar nodules displayed regions of partial or no ciliation on their surface. SEM and stereomicroscopic observations showed fine longitudinal mucosal folding throughout the pharynx the distension of which, together with the large capacity for mucus production (produced by intraepithelial glands and mucus secreting glands), would facilitate the swallowing of large chunks of food in the living state. The ventrally situated laryngeal mound containing the slit-like glottis also displayed longitudinal folds and a ciliated epithelium. Anatomically, the oesophagus could be divided into two clear regions. The cranial, approximate two-thirds appeared broad and flabby. At the tracheal bifurcation, the oesophagus narrowed significantly and indicated a greater muscular content, confirmed by light microscopy. LM and SEM examination of the oesophagus, however, revealed three regional components, viz., the cranial, mid- and caudal regions. In the cranial region, the epithelium was densely ciliated with intervening goblet cells being present. In the mid-region the ciliated component decreased with a concomitant increase in the goblet cell component. In the caudal region there was a further decrease in the number of ciliated cells and a higher concentration of goblet cells. Transmission electron microscopy (TEM) of the ciliated component of the oesophagus showed typical ultrastructural features of both the ciliated and goblet cells. / Dissertation (MSc (Veterinary Science))--University of Pretoria, 2002. / Anatomy and Physiology / unrestricted

No description available.

No description available.

No description available.