LDOC-1 and PARP-1 mRNA expression in leukocytes of father and son with cutaneous malignant melanoma

Abstract Apoptosis is central to the biology of cutaneous malignant melanoma (CMM). The leucine zipper, down regulated in cancer 1 (LDOC-1) gene, is known to be a regulator of the nuclear factor kappa B (NF-kB) through inhibition of the same NF-kB. The poly (ADP-ribose) polymerase-1 (PARP1) gene plays an important role for the efficient maintenance of genome integrity. PARP-1 protein is required for the apoptosis-inducing factor (AIF) translocation from the mitochondria to the nucleus. We report here two interesting cases of family melanoma, a father and son 84 and 40 years old, respectively. The histological evaluation of the lesions of both men revealed diffused superficial melanoma with epithelioid cells. We evaluated the differential expression of LDOC-1 and PARP-1 mRNA in peripheral blood leukocytes of both the father and son. We found that both LDOC-1 and PARP-1 genes were down-regulated in both patients compared with those of controls. These data suggest that low levels of expression of LDOC-1 and PARP-1 mRNA may be associated with familial melanoma

Accuracy of 3 Tesla pelvic phased-array multiparametric MRI in diagnosing prostate cancer at repeat biopsy.

Introduction. Multiparametric pelvic magnetic resonance imaging (mpMRI) accuracy in prostate cancer (PCa) diagnosis was evaluated. Materials and Methods. From June 2011 to December 2013, 168 patients (median 65 years) with negative digital rectal examination underwent repeat transperineal saturation biopsy (SPBx; median 28 cores) for persistently high or increasing PSA values, PSA >10 ng/ml or PSA values between 4.1-10 o r 2.6-4 ng/ml with free/total PSA < 25% and < 20%, respectively. All patients underwent mpMRI using a 3.0 Tesla scanner equipped with surface 16 channels phased-array coil and lesions suspicious for PCa were submitted to additional targeted biopsies. Results. A T1c PCa was found in 66 (39%) cases; SPBx and mpMRI-suspicious targeted biopsy diagnosed 60 (91%) and 52 (78.8%) cancers missing 6 (all of the anterior zone) and 14 cancers (12 and 2 of the lateral margins and anterior zone), respectively; in detail, mpMRI missed 12 (18.1%) PCa charaterized by microfocal (1 positive core with greatest percentage of cancer and Gleason score equal to 5% and 6, respectively) disease at risk for insignificant cancer. The diameter of the suspicious mpMRI lesion was directly correlated to the diagnosis of PCa with poor Gleason score (p < 0.05); detection rate of cancer for each suspicious mpMRI core was 35.3%. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive value of mpMRI in diagnosing PCa was 75.7%, 82.5%, 71.8%, 78.9%, 87.9%, respectively. Conclusion. Multiparametric pMRI improved SPBx accuracy in diagnosing significant anterior PCa; the diameter of mpMRI suspicious lesion resulted significantly predictive of aggressive cancers

Cerebellar degeneration-related protein 1 expression in fibroblasts of patients affected by down syndrome

Down syndrome (DS) is the most common genetic cause of intellectual disability, resulting from lack of disjunction of sister chromatids of human chromosome 21 or not partial disjunction of chromoso..

Poly (ADP-ribose) polymerase 1 expression in fibroblasts of Down syndrome subjects

Abstract Down syndrome (DS) is the most common chromosomal disorder. It is featured by intellectual disability and is caused by trisomy 21. People with DS can develop some traits of Alzheimer disease at an earlier age than subjects without trisomy 21. Apoptosis is a programmed cell death process under both normal physiological and pathological conditions. Poly (ADP-ribose) polymerase 1 is a mediator of programmed-necrotic cell death and appears to be also involved in the apoptosis. The aim of the present work was to detect the intracellular distribution of PARP-1 protein using immunofluorescence techniques and the expression of PARP-1 mRNA in culture of fibroblasts of DS subjects. The analysis of the intracellular distribution of PARP-1 show a signal at the nuclear level in about 75 % of the cells of DS subjects with a slight uniformly fluorescent cytoplasm. In contrast, in about 65% of the analyzed fibroblasts of the normal subjects only a slight fluorescent was found. These observations have been confirmed by PARP-1 gene mRNA expression evaluation. The data obtained from this study strengthen the hypothesis that the over-expression of PARP-1 gene could have a role in the activation of the apoptotic pathways acting in the neurodegenerative processes in DS

LDOC1 expression in fibroblasts of patients with Down syndrome

Abstract Down syndrome (DS) is characterised by intellectual disability and is caused by trisomy 21. Apoptosis is a programmed cell death process and is involved in neurodegenerative diseases such as Alzheimer. People with DS can develop some traits of Alzheimer disease at an earlier age than subjects without trisomy 21. The leucine zipper, down regulated in cancer 1 (LDOC1) appears to be involved in the apoptotic pathways. The aim of the present work was to detect the presence of intracellular synthesis of LDOC1 protein and LDOC1 mRNA in fibroblast cultures from DS subjects. The western blot shows the presence of LDOC1 protein in fibroblasts of DS subjects but no evidence of LDOC1 protein in fibroblasts of normal subjects. LDOC1 gene mRNA expression is increased in fibroblasts from DS subjects compared to fibroblasts from normal subjects. The data obtained from this study strengthen the hypothesis that the over-expression of LDOC1 gene could play a role in determining the phenotype of individuals with DS but does not exclude that this results from apoptotic mechanisms

Microchimerism in multiple sclerosis: The association between sex of offspring and MRI features in women with multiple sclerosis

Aims: During pregnancy, fetal cells can migrate to the mother via blood circulation. A percentage of these cells survive in maternal tissues for decades generating a population of fetal microchimeric cells (fMCs), whose biological role is unclear. The aim of this study was to investigate the association between the sex of offspring, an indirect marker of fMCs, and magnetic resonance imaging (MRI) features in women with multiple sclerosis (MS). Methods: We recruited 26 nulliparous MS patients (NPp), 20 patients with at least one male son (XYp), and 8 patients with only daughters (XXp). Each patient underwent brain MR scan to acquire 3D-T2w FLAIR FatSat and 3D-T1w FSPGR/TFE. Lesion Segmentation Tool (LST) and FreeSurfer were used to obtain quantitative data from MRI. Additional data were collected using medical records. Multiple regression models were applied to evaluate the association between sex of offspring and MS data. Results: Comparing NPp and XXp, we found that NPp had larger 4th ventricle volume (2.02 ± 0.59 vs. 1.70 ± 0.41; p = 0.022), smaller left entorhinal volume (0.55 ± 0.17 vs. 0.68 ± 0.25; p = 0.028), and lower thickness in the following cortical areas: left paracentral (2.34 ± 0.16 vs. 2.39 ± 0.17; p = 0.043), left precuneus (2.27 ± 0.11 vs. 2.34 ± 0.16; p = 0.046), right lateral occipital (2.14 ± 0.11 vs. 2.25 ± 0.08; p = 0.006). NPp also had lower thickness in left paracentral cortex (2.34 ± 0.16 vs. 2.46 ± 0.17; p = 0.004), left precalcarine cortex (1.64 ± 0.14 vs. 1.72 ± 0.12; p = 0.041), and right paracentral cortex (2.34 ± 0.17 vs. 2.42 ± 0.14; p = 0.015) when compared to XYp. Comparing XYp and XXp, we found that XYp had higher thickness in left cuneus (1.80 ± 0.14 vs. 1.93 ± 0.10; p = 0.042) and left pericalcarine areas (1.59 ± 0.19 vs. 1.72 ± 0.12; p = 0.032) and lower thickness in right lateral occipital cortex (2.25 ± 0.08 vs. 2.18 ± 0.13; p = 0.027). Discussion: Our findings suggested an association between the sex of offspring and brain atrophy. Considering the sex of offspring as an indirect marker of fMCs, we speculated that fMCs could accumulate in different brain areas modulating MS neuropathological processes

Flood quantiles scaling with upper soil hydraulic properties for different land uses at catchment scale

[EN] Changes in land use within a catchment are among the causes of non-stationarity in the flood regime, as they modify the upper soil physical structure and its runoff production capacity. This paper analyzes the relation between the variation of the upper soil hydraulic properties due to changes in land use and its effect on the magnitude of peak flows: (1) incorporating fractal scaling properties to relate the effect of the static storage capacity (the sum of capillary water storage capacity in the root zone, canopy interception and surface puddles) and the upper soil vertical saturated hydraulic conductivity on the flood regime; (2) describing the effect of the spatial organization of the upper soil hydraulic properties at catchment scale; (3) examining the scale properties in the parameters of the Generalized Extreme Value (GEV) probability distribution function, in relation to the upper soil hydraulic properties. This study considered the historical changes of land use in the Combeima River catchment in South America, between 1991 and 2007, using distributed hydrological modeling of daily discharges to describe the hydrological response. Through simulation of land cover scenarios, it was demonstrated that it is possible to quantify the magnitude of peak flows in scenarios of land cover changes through its Wide-Sense Simple Scaling with the upper soil hydraulic properties.This research was funded partially by the COLCIENCIAS 567 doctoral fellowship program, Universidad del Tolima project 1300213 and Universidad de Ibague (Colombia) project 12-262-COL00, and by Universitat Politecnica de Valencia (Spain) and by the Spanish Research Project ECO-TETIS (ref. CGL2011-28776-C02-01) and TETIS-MED (ref. CGL2014-58127-C3-3-R). Thanks to The Shuttle Radar Topography Mission NASA, IDEAM and IGAC in Colombia, for providing digital elevation model, streamflow, rainfall data, and soil study of the Tolima Region.Peña-Rojas, LE.; Barrios Peña, MI.; Francés, F. (2016). Flood quantiles scaling with upper soil hydraulic properties for different land uses at catchment scale. Journal of Hydrology. 541:1258-1272. https://doi.org/10.1016/j.jhydrol.2016.08.031S1258127254

Cardiovascular magnetic resonance for the assessment of patients undergoing transcatheter aortic valve implantation: a pilot study

<p>Abstract</p> <p>Background</p> <p>Before trans-catheter aortic valve implantation (TAVI), assessment of cardiac function and accurate measurement of the aortic root are key to determine the correct size and type of the prosthesis. The aim of this study was to compare cardiovascular magnetic resonance (CMR) and trans-thoracic echocardiography (TTE) for the assessment of aortic valve measurements and left ventricular function in high-risk elderly patients submitted to TAVI.</p> <p>Methods</p> <p>Consecutive patients with severe aortic stenosis and contraindications for surgical aortic valve replacement were screened from April 2009 to January 2011 and imaged with TTE and CMR.</p> <p>Results</p> <p>Patients who underwent both TTE and CMR (n = 49) had a mean age of 80.8 ± 4.8 years and a mean logistic EuroSCORE of 14.9 ± 9.3%. There was a good correlation between TTE and CMR in terms of annulus size (R²= 0.48, p < 0.001), left ventricular outflow tract (LVOT) diameter (R²= 0.62, p < 0.001) and left ventricular ejection fraction (LVEF) (R²= 0.47, p < 0.001) and a moderate correlation in terms of aortic valve area (AVA) (R²= 0.24, p < 0.001). CMR generally tended to report larger values than TTE for all measurements. The Bland-Altman test indicated that the 95% limits of agreement between TTE and CMR ranged from -5.6 mm to + 1.0 mm for annulus size, from -0.45 mm to + 0.25 mm for LVOT, from -0.45 mm²to + 0.25 mm²for AVA and from -29.2% to 13.2% for LVEF.</p> <p>Conclusions</p> <p>In elderly patients candidates to TAVI, CMR represents a viable complement to transthoracic echocardiography.</p

Advanced Virgo Plus: Future Perspectives

While completing the commissioning phase to prepare the Virgo interferometer for the next joint Observation Run (O4), the Virgo collaboration is also finalizing the design of the next upgrades to the detector to be employed in the following Observation Run (O5). The major upgrade will concern decreasing the thermal noise limit, which will imply using very large test masses and increased laser beam size. But this will not be the only upgrade to be implemented in the break between the O4 and O5 observation runs to increase the Virgo detector strain sensitivity. The paper will cover the challenges linked to this upgrade and implications on the detector's reach and observational potential, reflecting the talk given at 12th Cosmic Ray International Seminar - CRIS 2022 held in September 2022 in Napoli