Cardiac Surgery in Patients With Liver Cirrhosis (CASTER) Study: Early and Long-Term Outcomes

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Iloprost use and medical management of systemic sclerosis-related vasculopathy in Italian tertiary referral centers: results from the PROSIT study

Clinical and Experimental Medicine - Vasculopathy is a crucial feature of systemic sclerosis (SSc), and Raynaud’s phenomenon (RP) and digital ulcers (DU) have a deep impact on the quality of...     

Common fragile site instability in normal cells: Lessons and perspectives

Mechanisms and events related to common fragile site (CFS) instability are well known in cancer cells. Here, we argue that normal cells remain an important experimental model to address questions related to CFS instability in the absence of alterations in cell cycle and DNA damage repair pathways, which are common features acquired in cancer. Furthermore, a major gap of knowledge concerns the stability of CFSs during gametogenesis. CFS instability in meiotic or postmeiotic stages of the germ cell line could generate chromosome deletions or large rearrangements. This in turn can lead to the functional loss of the several CFS‐associated genes with tumor suppressor function. Our hypothesis is that such mutations can potentially result in genetic predisposition to develop cancer. Indirect evidence for CFS instability in human germ cells has been provided by genomic investigations in family pedigrees associated with genetic disease. The issue of CFS instability in the germ cell line should represent one of the future efforts, and may take advantage of the existence of sequence and functional conservation of CFSs between rodents and humans.     

The intra-oral effect on enamel demineralization of extracellular matrix material synthesized from sucrose by Streptococcus mutans

The role of extracellular matrix material (EMM) synthesized from sucrose (S) by Streptococcus mutans IB-1600 in altering the demineralizing potential of artificial plaque was evaluated with an intraoral enamel demineralization test (IEDT). The artificial plaque samples were prepared from cells cultivated in Todd-Hewitt broth (THB) supplemented with various S concentrations and by mixing THB-grown cells with increasing proportions of EMM (heat-killed THB + 2% S-cultivated cells). The samples were also evaluated for cell density (DNA content) and acidogenicity in vitro (pH-stat), as well as for in situ pH changes during a 45-minute intra-oral test following a 10% glucose rinse. An increase in the proportion of EMM relative to cell density was associated with an increase in enamel demineralization. This trend reversed when the ratio of cells to EMM was less than 1:19. Experiments involving strains of S. mitis, S. sanguis, and S. salivarius suggested a similar effect of EMM. The intra-oral pH data suggest that the presence of EMM may enhance demineralization by altering diffusion properties of plaque.     

Craniectomy and noggin application in an infant model.

INTRODUCTION: Noggin is an antagonist of bone morphogenetic proteins (BMP)-2, -4 and -7. Little data are available regarding its clinical utility. Two hypotheses were put forward: firstly, that spontaneous regeneration of calvarial defects with noggin protein would result in diminished bone volume when compared with calvarial defects not so treated. Secondly, that centrifugal cranial expansion would remain undisturbed whether noggin was applied or not. MATERIAL AND METHODS: A unilateral defect of the frontal and parietal bones (2x4cm) was generated by excising the right coronal suture in 2-month-old minipigs (n=10) and in group 1 (n=5) no further intervention was undertaken. In the second group (n=5), a collagen type I tissue fleece and noggin protein (1.05mg/ml) were applied. After 4 months the coronal suture regions of frontal sides were examined in each animal by computed tomography and non-decalcified histology. RESULTS: Bony gaps of equivalent size remained in animals of both groups. The differences in bone volumes of the experimental sides of group 1 were not statistically significantly different (p=0.117) when compared with those of group 2. A significant difference in the bone volumes of the experimental versus control (unoperated) sides was found in both group 1 (p=0.043) and group 2 (p=0.043). Internal skull diameters increased by 16.4% in both groups but the physiological centrifugal cranial expansion remained undisturbed. Bone densities of the experimental and control sides of groups 1 and 2 were not statistically significantly different (both p>0.05). CONCLUSIONS: The first hypothesis was contradicted: the quantity and quality of spontaneous bone regenerates was not altered by application of noggin protein. The second hypothesis was confirmed: no disruption of subsequent cranial development was seen. It may be that a single application of noggin protein in this study was insufficient. However, it may well be suggested that the continuous supplementation of noggin, for example by adenoviral noggin gene transfer may significantly reduce the quantity of spontaneous bone regeneration in a similar experiment.     

Validation of FreeSurfer-Estimated Brain Cortical Thickness: Comparison with Histologic Measurements

FreeSurfer software package automatically estimates the cerebral cortical thickness. Its use is widely accepted, albeit this tool was validated against histologic measurements in only two post-mortem isolated brain MR scans. Indeed, a comparison between histologic measurements and FreeSurfer estimation from in vivo data was never performed. At the “Claudio Munari” Center for Epilepsy and Parkinson Surgery we have included FreeSurfer in our presurgical workflow since 2008, mainly because the automatic reconstruction of the brain surface is useful for carefully planning the surgical resection. We therefore compared cortical thickness values obtained by the automatic software pipeline with manual histologic measurements performed on 27 histologic specimens resected from the corresponding brain regions of the same epileptic subjects. This method-comparison study, including Passing–Bablok regression and Bland-Altman plot analysis, showed a good agreement between FreeSurfer estimation and histologic measurements of cortical thickness. The mean cortical thickness values (±Standard Deviation) obtained with FreeSurfer and histologic measurements were 3.65 mm?±?0.44 and 3.72 mm?±?0.36, respectively (P value?=?0.32). Our findings strengthen previous reports on cortical thickness changes as biomarkers of different neurological conditions.