Reference Limits of Plasma Fibrinogen

Peer Reviewe

An accurate approach for computational pKa determination of phenolic compounds

Computational chemistry is a valuable tool, as it allows for in silico prediction of key parameters of novel compounds, such as pKa. In the framework of computational pKa determination, the literature offers several approaches based on different level of theories, functionals and continuum solvation models. However, correction factors are often used to provide reliable models that adequately predict pKa. In this work, an accurate protocol based on a direct approach is proposed for computing phenols pKa. Importantly, this methodology does not require the use of correction factors or mathematical fitting, making it highly practical, easy to use and fast. Above all, DFT calculations performed in the presence two explicit water molecules using CAM-B3LYP functional with 6-311G+dp basis set and a solvation model based on density (SMD) led to accurate pKa values. In particular, calculations performed on a series of 13 differently substituted phenols provided reliable results, with a mean absolute error of 0.3. Furthermore, the model achieves accurate results with -CN and -NO2 substituents, which are usually excluded from computational pKa studies, enabling easy and reliable pKa determination in a wide range of phenols

Generation of a flat-top laser beam for gravitational wave detectors by means of a nonspherical Fabry-Perot resonator

We have tested a new kind of Fabry-Perot long-baseline optical resonator proposed to reduce the thermal noise sensitivity of gravitational wave interferometric detectors--the "mesa beam" cavity--whose flat top beam shape is achieved by means of an aspherical end mirror. We present the fundamental mode intensity pattern for this cavity and its distortion due to surface imperfections and tilt misalignments, and contrast the higher order mode patterns to the Gauss-Laguerre modes of a spherical mirror cavity. We discuss the effects of mirror tilts on cavity alignment and locking and present measurements of the mesa beam tilt sensitivity

Prolyl 3‐hydroxylase 2 is a molecular player of angiogenesis

Prolyl 3‐hydroxylase 2 (P3H2) catalyzes the post‐translational formation of 3‐ hydroxyproline on collagens, mainly on type IV. Its activity has never been directly associated to angiogenesis. Here, we identified P3H2 gene through a deep‐sequencing transcriptome analysis of human umbilical vein endothelial cells (HUVECs) stimulated with vascular endothelial growth factor A (VEGF‐A). Differently from many previous studies we carried out the stimulation not on starved HUVECs, but on cells grown to maintain the best condition for their in vitro survival and propagation. We showed that P3H2 is induced by VEGF‐A in two primary human endothelial cell lines and that its transcription is modulated by VEGF‐A/VEGF receptor 2 (VEGFR‐2) signaling pathway through p38 mitogen‐activated protein kinase (MAPK). Then, we demonstrated that P3H2, through its activity on type IV Collagen, is essential for angiogenesis properties of endothelial cells in vitro by performing experiments of gain‐ and loss‐of‐function. Immunofluorescence studies showed that the overexpression of P3H2 induced a more condensed status of Collagen IV, accompanied by an alignment of the cells along the Collagen IV bundles, so towards an evident pro‐angiogenic status. Finally, we found that P3h2 knockdown prevents pathological angiogenesis in vivo, in the model of laser‐induced choroid neovascularization. Together these findings reveal that P3H2 is a new molecular player involved in new vessels formation and could be considered as a potential target for anti‐angiogenesis therapy

Surgical Treatment with Locoregional Flap for the Nose

Nonmelanotic skin cancers (NMSCs) are the most frequent of all neoplasms and nasal pyramid represents the most common site for the presentation of such cutaneous malignancies, particularly in sun-exposed areas: ala, dorsum, and tip. Multiple options exist to restore functional and aesthetic integrity after skin loss for oncological reasons; nevertheless, the management of nasal defects can be often challenging and the best "reconstruction" is still to be found. In this study, we retrospectively reviewed a total of 310 patients who presented to our Department of Plastic and Reconstructive Surgery for postoncological nasal reconstruction between January 2011 and January 2016. Nasal region was classified into 3 groups according to the anatomical zones affected by the lesion: proximal, middle, and distal third. We included an additional fourth group for complex defects involving more than one subunit. Reconstruction with loco regional flaps was performed in all cases. Radical tumor control and a satisfactory aesthetic and functional result are the primary goals for the reconstructive surgeon. Despite tremendous technical enhancements in nasal reconstruction techniques, optimal results are usually obtained when "like is used to repair like." Accurate evaluation of the patients clinical condition and local defect should be always considered in order to select the best surgical option

Towards the development of antioxidant cerium oxide nanoparticles for biomedical applications: Controlling the properties by tuning synthesis conditions

In this work CeO2 nanoparticles (CeO2-NPs) were synthesized through the thermal de-composition of Ce(NO3)3·6H2O, using as capping agents either octylamine or oleylamine, to evaluate the effect of alkyl chain length, an issue at 150 °C, in the case of octylamine and at 150 and 250 °C, in the case of oleylamine, to evaluate the effect of the temperature on NPs properties. All the nanoparticles were extensively characterized by a multidisciplinary approach, such as wide-angle X-ray diffraction, transmission electron microscopy, dynamic light scattering, UV-Vis, fluorescence, Raman and FTIR spectroscopies. The analysis of the experimental data shows that the capping agent nature and the synthesis temperature affect nanoparticle properties including size, morphology, aggregation and Ce3+/Ce4+ ratio. Such issues have not been discussed yet, at the best of our knowledge, in the literature. Notably, CeO2-NPs synthesized in the presence of oleylamine at 250 °C showed no tendency to aggregation and we made them water-soluble through a further coating with sodium oleate. The obtained nanoparticles show a less tendency to clustering forming stable aggregates (ranging between 14 and 22 nm) of few NPs. These were tested for biocompatibility and ROS inhibiting activity, demonstrating a remarkable antioxidant activity, against oxidative stress

Correction for Tarallo et al., “Altered Fecal Small RNA Profiles in Colorectal Cancer Reflect Gut Microbiome Composition in Stool Samples”

Dysbiotic configurations of the human gut microbiota have been linked to colorectal cancer (CRC). Human small noncoding RNAs are also implicated in CRC, and recent findings suggest that their release in the gut lumen contributes to shape the gut microbiota. Bacterial small RNAs (bsRNAs) may also play a role in carcinogenesis, but their role has been less extensively explored. Here, we performed small RNA and shotgun sequencing on 80 stool specimens from patients with CRC or with adenomas and from healthy subjects collected in a cross-sectional study to evaluate their combined use as a predictive tool for disease detection. We observed considerable overlap and a correlation between metagenomic and bsRNA quantitative taxonomic profiles obtained from the two approaches. We identified a combined predictive signature composed of 32 features from human and microbial small RNAs and DNA-based microbiome able to accurately classify CRC samples separately from healthy and adenoma samples (area under the curve [AUC] = 0.87). In the present study, we report evidence that host-microbiome dysbiosis in CRC can also be observed by examination of altered small RNA stool profiles. Integrated analyses of the microbiome and small RNAs in the human stool may provide insights for designing more-accurate tools for diagnostic purposes.IMPORTANCE The characteristics of microbial small RNA transcription are largely unknown, while it is of primary importance for a better identification of molecules with functional activities in the gut niche under both healthy and disease conditions. By performing combined analyses of metagenomic and small RNA sequencing (sRNA-Seq) data, we characterized both the human and microbial small RNA contents of stool samples from healthy individuals and from patients with colorectal carcinoma or adenoma. With the integrative analyses of metagenomic and sRNA-Seq data, we identified a human and microbial small RNA signature which can be used to improve diagnosis of the disease. Our analysis of human and gut microbiome small RNA expression is relevant to generation of the first hypotheses about the potential molecular interactions occurring in the gut of CRC patients, and it can be the basis for further mechanistic studies and clinical test

Altered Fecal Small RNA Profiles in Colorectal Cancer Reflect Gut Microbiome Composition in Stool Samples

Dysbiotic configurations of the human gut microbiota have been linked to colorectal cancer (CRC). Human small noncoding RNAs are also implicated in CRC, and recent findings suggest that their release in the gut lumen contributes to shape the gut microbiota. Bacterial small RNAs (bsRNAs) may also play a role in carcinogenesis, but their role has been less extensively explored. Here, we performed small RNA and shotgun sequencing on 80 stool specimens from patients with CRC or with adenomas and from healthy subjects collected in a cross-sectional study to evaluate their combined use as a predictive tool for disease detection. We observed considerable overlap and a correlation between metagenomic and bsRNA quantitative taxonomic profiles obtained from the two approaches. We identified a combined predictive signature composed of 32 features from human and microbial small RNAs and DNA-based microbiome able to accurately classify CRC samples separately from healthy and adenoma samples (area under the curve [AUC] = 0.87). In the present study, we report evidence that host-microbiome dysbiosis in CRC can also be observed by examination of altered small RNA stool profiles. Integrated analyses of the microbiome and small RNAs in the human stool may provide insights for designing more-accurate tools for diagnostic purposes.IMPORTANCE The characteristics of microbial small RNA transcription are largely unknown, while it is of primary importance for a better identification of molecules with functional activities in the gut niche under both healthy and disease conditions. By performing combined analyses of metagenomic and small RNA sequencing (sRNA-Seq) data, we characterized both the human and microbial small RNA contents of stool samples from healthy individuals and from patients with colorectal carcinoma or adenoma. With the integrative analyses of metagenomic and sRNA-Seq data, we identified a human and microbial small RNA signature which can be used to improve diagnosis of the disease. Our analysis of human and gut microbiome small RNA expression is relevant to generation of the first hypotheses about the potential molecular interactions occurring in the gut of CRC patients, and it can be the basis for further mechanistic studies and clinical test