Smad4 overexpression causes germ cell ablation and leydig cell hyperplasia in transgenic mice

Members of the transforming growth factor-beta (TGF-beta) superfamily play a variety of important roles in testicular development and function. The tumor suppressor gene, Smad4, is a common mediator of TGF-beta, activin, and bone morphogenetic protein-mediated signaling pathways. To investigate the role of the Smad4 gene during testicular development and function, transgenic mice were generated using a Flag-tagged Smad4 gene driven by 180-bp fragment of the Mullerian inhibiting substance upstream promoter sequence. Three Smad4 transgenic founders (A, B, and G) were detected by Southern blot analysis; line B showed the highest expression of the Smad4 transgene and was further studied. The fertility in F1 generation (B) and F2 generation (BB) of the Smad4 transgenic mice was not impaired. However, in the F3 generation (B2x) all animals were impacted by the overexpression of the Smad4 transgene and two kinds of phenotypes were observed. In one group animals were completely infertile, while in the other group animals were fertile and sired the normal number of pups/litter. These groups are designated as infertile and fertile in the text. Histological evaluation of the testes from the infertile group showed variable degrees of Leydig cell hyperplasia, apoptosis of germ cells, spermatogenic arrest, seminiferous tubule degeneration, and infertility. In the fertile group, there was no apparent change in the histology of the testis except for a slight increase in the number of Leydig cells. Serum follicle-stimulating hormone levels in the adult animals of both groups of Smad4 transgenic male mice were not significantly different from normal littermates; however, testosterone levels in both groups were significantly (P < 0.05) increased. These results suggest that overexpression of Smad4 leads to testicular abnormalities and infertility supporting the hypothesis that the TGF-beta signaling pathways are carefully orchestrated during testicular development. In the absence of normal levels of Smad4 testicular function is compromised.     

Temporal interactions of air-puff-evoked blinks and saccadic eye movements: insights into motor preparation

Following the initial, sensory response to stimulus presentation, activity in many saccade-related burst neurons along the oculomotor neuraxis is observed as a gradually increasing low-frequency discharge hypothesized to encode both timing and metrics of the impending eye movement. When the activity reaches an activation threshold level, these cells discharge a high-frequency burst, inhibit the pontine omnipause neurons (OPNs) and trigger a high-velocity eye movement known as saccade. We tested whether early cessation of OPN activity, prior to when it ordinarily pauses, acts to effectively lower the threshold and prematurely trigger a movement of modified metrics and/or dynamics. Relying on the observation that OPN discharge ceases during not only saccades but also blinks, air-puffs were delivered to one eye to evoke blinks as monkeys performed standard oculomotor tasks. We observed a linear relationship between blink and saccade onsets when the blink occurred shortly after the cue to initiate the movement but before the average reaction time. Blinks that preceded and overlapped with the cue increased saccade latency. Blinks evoked during the overlap period of the delayed saccade task, when target location is known but a saccade cannot be initiated for correct performance, failed to trigger saccades prematurely. Furthermore, when saccade and blink execution coincided temporally, the peak velocity of the eye movement was attenuated, and its initial velocity was correlated with its latency. Despite the perturbations, saccade accuracy was maintained across all blink times and task types. Collectively, these results support the notion that temporal features of the low-frequency activity encode aspects of a premotor command and imply that inhibition of OPNs alone is not sufficient to trigger saccades.     

Triglycidylamine crosslinking of porcine aortic valve cusps or bovine pericardium results in improved biocompatibility, biomechanics, and calcification resistance: chemical and biological mechanisms

We investigated a novel polyepoxide crosslinker that was hypothesized to confer both material stabilization and calcification resistance when used to prepare bioprosthetic heart valves. Triglycidylamine (TGA) was synthesized via reacting epichlorhydrin and NH(3). TGA was used to crosslink porcine aortic cusps, bovine pericardium, and type I collagen. Control materials were crosslinked with glutaraldehyde (Glut). TGA-pretreated materials had shrink temperatures comparable to Glut fixation. However, TGA crosslinking conferred significantly greater collagenase resistance than Glut pretreatment, and significantly improved biomechanical compliance. Sheep aortic valve interstitial cells grown on TGA-pretreated collagen did not calcify, whereas sheep aortic valve interstitial cells grown on control substrates calcified extensively. Rat subdermal implants (porcine aortic cusps/bovine pericardium) pretreated with TGA demonstrated significantly less calcification than Glut pretreated implants. Investigations of extracellular matrix proteins associated with calcification, matrix metalloproteinases (MMPs) 2 and 9, tenascin-C, and osteopontin, revealed that MMP-9 and tenascin-C demonstrated reduced expression both in vitro and in vivo with TGA crosslinking compared to controls, whereas osteopontin and MMP-2 expression were not affected. TGA pretreatment of heterograft biomaterials results in improved stability compared to Glut, confers biomechanical properties superior to Glut crosslinking, and demonstrates significant calcification resistance.     

Patient preferences for shared decisions: a systematic review

Objectives

Empirical literature on patient decision role preferences regarding treatment and screening was reviewed to summarize patients’ role preferences across measures, time and patient population.

Methods

Five databases were searched from January 1980 to December 2007 (1980-2007 Ovid MEDLINE, Cochrane Database of Systematic Reviews, PsychInfo, Web of Science and PubMed (2005-2007)). Eligible studies measured patient decision role preferences, described measures, presented findings as percentages or mean scores and were published in English from any country. Studies were compared by patient population, time of publication, and measure.

Results

115 studies were eligible. The majority of patients preferred sharing decisions with physicians in 63% of the studies. A time trend appeared. The majority of respondents preferred sharing decision roles in 71% of the studies from 2000 and later, compared to 50% of studies before 2000. Measures themselves, in addition to patient population, influenced the preferred decision roles reported.

Conclusion

Findings appear to vary with the measure of preferred decision making used, time of the publication and characteristics of the population.

Practice implications

The role preference measure itself must be considered when interpreting patient responses to a measure or question about a patient's preference for decision roles.     

Novel combined miniature optical coherence tomography ultrasound probe for in vivo intravascular imaging

We have developed a miniature integrated optical coherence tomography (OCT) ultrasound (US) probing system for intravascular imaging applications. In the OCT probe, the light coming out of a single mode fiber is focused by a gradient-index lens and then reflected by a right-angle prism from the side of the probe into the sample. It was combined with a 35 MHz PMN-PT side-viewing ultrasound transducer to obtain the ultrasound image as well. The OCT and ultrasound probes were integrated as a single probe to obtain OCT and ultrasound images simultaneously. The integrated probe has an outer diameter of 0.69 mm which, to our knowledge, is the smallest integrated OCT-US probe reported. Fast data acquisition and processing was implemented for real-time imaging. In vitro OCT and US images of human coronary artery with pathology, as well as in vivo images of normal rabbit abdominal aorta, were obtained using the integrated OCT-US probe to demonstrate its capability.