BACKGROUND Voiding disorders in humans, particularly in children are associated with increased incidence of behavioral issues as well as past history of childhood abuse. We hypothesized that creating stress in mice, utilizing either a chronic social defeat model (SD) or restraint stress in shallow water model (RSSW), would engender changes in bladder function, morphology, and behavior, thereby enabling us to study the resultant voiding dysfunction. METHODS For SD stress (14 days), C57BL/6 male mice were exposed daily to a larger aggressive CD-1 male for 10 minutes, followed by sensory exposure in a barrier cage for 24 hours. Control mice were similarly housed with no exposure. For RSSW (21 days), C57BL/6 mice were put in a perforated conical tube with feet immersed in water daily for 4 hours, then returned to single housing cages. Control mice were also in single housing. After the stress period, voiding patterns were obtained on filter paper, followed by behavioral tests. At necropsy, blood was taken for corticosterone analysis, and bladder and body weights measured. Bladder cryosections were stained with hematoxylin and eosin (H&E) for morphological assessment. Sequential sections were immunostained with antibodies to Ki-67 as a proliferation marker, CD31 (endothelial cell marker), and Uroplakin-II. Image J software was used to measure bladder wall thickness on blinded H&E photomicrographs as well as quantitate CD31 staining. Both Ki-67 -positive and -negative nuclei were counted with Imaris software to obtain a proliferation index. RESULTS Only SD mice had a single large void pattern. Bladder -to -body weight ratios increased in SD mice (p≤ 0.02) but not in RSSW mice. Plasma corticosterone levels were elevated in all stressed mice. SD mice exhibited lower levels of locomotor activity compared with controls; RSSW mice were hyperactive. In SD mice, bladder wall thickness was increased (p ≤ 0.003) but no change was seen in Ki-67 proliferation index, consistent with hypertrophy. No difference with control mice was seen in vascularity as visualized by CD31 staining. Uniform Uroplakin-II staining lined the urothelium of both SD and control mice. CONCLUSIONS Mice exposed to repeated SD (14 days) respond with altered voiding indicative of urine retention, and exhibit bladder wall changes consistent with hypertrophy while the urothelial barrier is maintained. These changes were not observed with repeated RSSW. SD, in contrast to RSSW, provides a model of psychological stress to further study the interplay of behavior and bladder dysfunction, enabling an improved understanding of voiding dysfunction, and the ability to create innovative and more effective management pathways for children who present with voiding dysfunction.
In 1997 Lasmo Oil Pakistan Ltd (Lasmo) gained a significant position in the offshore Indus Basin with the award of the Indus A and B Blocks. The main hydrocarbon play comprises Miocene shelf-delta sands interbedded with intraformational shale seals and sourced by gas-prone offshore equivalents. Approximately 12 000 km of seismic data have been interpreted in the detailed evaluation of these blocks. However, only four wells have tested the preferred play type and no core or rock data were available to provide further insights into facies or age dating. Log data from two key wells in the offshore Indus area record the initial infilling of the basin by shale-dominated basinal or outer shelf sediments, followed by stacked thin-bedded sandstone-shale sequences of a shelf-delta nature. A zone of progradational sequences marks the transition between the two, but no other workable stratigraphic divisions were apparent. Regional seismic correlation established the diachronous nature of the prograding shelf package and this was matched by distinct bands of seismic progrades. A series of simple palaeogeographies of the prograding shelf margin were developed showing initial sediment input from the north and rapid progradation towards the south and west. The Oligo-Miocene basin fill of the offshore Indus Basin appears to be a ‘one-step’ fill process of a significant depocentre created between the Karachi Platform and the Murray Ridge. Canyons are a very distinct feature on seismic profiles and two main phases of development are apparent. The earlier phase is interpreted to be of Early Miocene age. Downcutting at this time rarely exceeded 400 m. The second phase of canyon development occurred during Plio-Pleistocene time, and these younger canyons often dominate the shallow section, with multiple phases of downcutting sometimes exceeding 1000 m. Where drilled, canyons of both ages have been found to be shale prone. These drilled canyons are interpreted to be on the palaeo-slope where erosion and sediment by-pass occurred during the active phase, and were subsequently filled by fine-grained deposits after abandonment. The two phases of canyoning are considered to relate to phases of tectonic activity in the collision zone between the western margin of the Indo-Pakistan plate and the Eurasian plate.
There are significant differences in urine calcium-to-citrate ratios between solitary and recurrent calcium stone forming children. Solitary stone formers trended higher compared to controls. These findings may allow more precise risk stratification and treatment to prevent recurrent stone episodes.
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