Pectoral nerves blocks (PECS) and sedation: A way to avoid general anesthesia in breast surgery - A single institution early experience.

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Comparison of Monocyte Distribution Width (MDW) and Procalcitonin for early recognition of sepsis

We carried out a prospective observational study to evaluate whether Monocyte Distribution Width (MDW) may play a role in identifying patients with sepsis in comparison with Procalcitonin (PCT). We prospectively enrolled all consecutive patients hospitalized at the Infectious Diseases Unit of Pescara General Hospital for bacterial infection or sepsis. MDW values were collected for all patients. Clinical characteristics, demographic data, past and present medical history, microbiological results, PCT, as well as neutrophil and monocytes indices at entry were compared in the 2 groups. Two-hundred-sixty patients were enrolled, 63.5% males, aged 59.1±19.5 years. Sepsis was diagnosed in 105 (40.4%); in 60 (57.1%) at least 1 microorganism was isolated from blood cultures. In multivariate models, MDW as a continuous variable (OR:1.57 for each unit increase; 95%CI: 1.31-1.87, p<0.001) and PCT˃1 ng/mL (OR: 48.5; 95%CI: 14.7-160.1, p<0.001) were independently associated with sepsis. Statistical best cut points associated with sepsis were 22.0 for MDW and 1.0 ng/mL for PCT whereas MDW values<20 were invariably associated with negative blood cultures. At ROC curve analysis, the AUC of MDW (0.87) was nearly overlapping that of PCT (0.88). Our data suggest that incorporating MDW within current routine WBC counts and indices may be of remarkable use for detection of sepsis. Further research is warranted

Morphometric analysis of lymphatics vessels in fibrotic human lung

In pulmonary fibrosis, the usual interstitial pneumonia (UIP) pattern is characterised by heterogeneous, patchy fibrosis, with areas of normal lung adjacent to areas of complete destruction (honeycombing) and by fibroblastic foci (FF). The NSIP pattern which is characteristic of systemic sclerosis, is characterised by a more homogeneous involvement of the lung without honeycombing and FF. Little is known on lymphatic vessels in lung fibrosis. Defective lymphatic clearance could lead to prolonged exposure to pathogenic antigens and/or pro-inflammatory/pro-fibrotic mediators. We evaluated the distribution and morphology of lymphatic vessels in lung biopsies of 6 patients with UIP, 6 NSIP and 5 controls. Consecutive sections were stained with Movat’s pentachrome and with double immunostaining for von Willebrand factor and podoplanin (D2-40). Area, perimeter and position were recorded for vessels with a diameter > 5µm. We investigated separately in lintralobular, sub-pleural, and interlobular spaces. Lymphatics were consistently larger in subpleural spaces and in interlobular septa than in intralobular tissue. In the latter, the density of lymphatic vessels was significantly reduced in NSIP and in UIP (both 21±1 mm-2) compared to controls (35±4 mm-2) . In controls, 85±6% of the intralobular lymphatics were close (< 100 µm) to a blood vessel, and only 5±4% were in the proximity of bronchoalveolar spaces, while in the disease groups they were less frequently perivascular (NSIP 55 ±3%, UIP 56 ±2%) and more frequently associated with the bronchoalveolar lumen (NSIP 85 ±3%, UIP 69 ±2%). By contrast, in interlobular septa, lymphatic density was significantly increased in NSIP (303±28 mm-2) and in UIP (286±124 mm-2) compared to controls (96±69 mm-2). No differences in lymphatic density was seen in subpleural spaces. Thus, our data show a marked redistribution of lymphatic vessels within the lung in pulmonary fibrosis, without noticeable differences between the NSIP and UIP patterns

Genetic determinants in a critical domain of ns5a correlate with hepatocellular carcinoma in cirrhotic patients infected with hcv genotype 1b

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain‐1 interacts with cellular proteins inducing pro‐oncogenic pathways. Thus, we explore genetic variations in NS5A domain‐1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype‐1b infected DAA‐naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7–82.3); p < 0.001). Focusing on HCC‐group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4–6.2) log IU/mL vs. 5.3 (4.4–5.6) log IU/mL, p = 0.02) and lower ALT (35 (30–71) vs. 83 (48–108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell‐cycle regulation (p53, p85‐PIK3, and β‐ catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV‐mediated oncogenesis. The role of these NS5A domain‐1 mutations in triggering pro‐oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation

Cortina d'Ampezzo: storia, arte e turismo

Lo scopo di questo progetto di tesi magistrale è quello di studiare la situazione storica, artistica, culturale, religiosa e turistica di Cortina d’Ampezzo, evidenziando quali sono i punti di forza di questo luogo ed inoltre cercare di capire come il sistema turistico è stato attuato e percepito nel territorio di Cortina. Questo lavoro è suddiviso in cinque capitoli: il primo momento riguarda le Dolomiti e Cortina d’Ampezzo: la descrizione dell’ambiente, del clima, degli aspetti naturali, oltre all’analisi geografica. Il secondo momento riguarda la storia di Cortina d’Ampezzo dalle origini fino ai giorni nostri, con un’attenzione particolare verso la cultura, l’arte, lo spettacolo. Il terzo momento riguarda il turismo a Cortina d’Ampezzo nei vari aspetti, in particolare quello turistico e quello religioso. Il quarto momento, invece, riguarda l’indagine sulla consistenza alberghiera a Cortina d’Ampezzo dal Novecento ai giorni nostri. Il quinto momento riguarda l’andamento degli arrivi e delle presenze a Cortina dall’inizio del Novecento ad oggi

Morphometric analysis of intralobular, interlobular and pleural lymphatics in normal human lung

In spite of their presumed relevance in maintaining interalveolar septal fluid homeostasis, the knowledge of the anatomy of human lung lymphatics is still incomplete. The recent discovery of reliable markers specific for lymphatic endothelium has led to the observation that, contrary to previous assumptions, human lymphatic vessels extend deep inside the pulmonary lobule in association with bronchioles, intralobular arterioles or small pulmonary veins. The aim of this study was to provide a morphometric characterization of lymphatic vessels in the periphery of the human lung. Human lung sections were immunolabelled with the lymphatic marker D2-40, followed by blood vessel staining with von Willebrand Factor. Lymphatic vessels were classified into: intralobular (including those associated with bronchovascular bundles, perivascular, peribronchiolar and interalveolar), pleural (in the connective tissue of the visceral pleura), and interlobular (in interlobular septa). The percentage area occupied by the lymphatic lumen was much greater in the interlobular septa and in the subpleural space than in the lobule. Most of the intralobular lymphatic vessels were in close contact with a blood vessel, either alone or within a bronchovascular bundle, whereas 7\% were associated with a bronchiole and < 1\% were not connected to blood vessels or bronchioles (interalveolar). Intralobular lymphatic size progressively decreased from bronchovascular through to peribronchiolar, perivascular and interalveolar lymphatics. Lymphatics associated with bronchovascular bundles had similar morphometric characteristics to pleural and interlobular lymphatics. Shape factors were similar across lymphatic populations, except that peribronchiolar lymphatics had a marginally increased roundness and circularity, suggesting a more regular shape due to increased filling, and interlobular lymphatics had greater elongation, due to a greater proportion of conducting lymphatics cut longitudinally. Unsupervised cluster analysis confirmed a marked heterogeneity of lymphatic vessels both within and between groups, with a cluster of smaller vessels specifically represented in perivascular and interalveolar lymphatics within the alveolar interstitium. Our data indicate that intralobular lymphatics are a heterogeneous population, including vessels surrounding the bronchovascular bundle analogous to the conducting vessels present in the pleural and interlobular septa, many small perivascular lymphatics responsible for maintaining fluid balance in the alveolar interstitium, and a minority of intermediate lymphatics draining the peripheral airways. These lymphatic populations could be differentially involved in the pathogenesis of diseases preferentially involving distinct lung compartments

(R)-α-lipoyl-glycyl-L-prolyl-L-glutamyl dimethyl ester codrug as a multifunctional agent with potential neuroprotective activities

The (R)-α-lipoyl-glycyl-L-prolyl-L-glutamyl dimethyl ester codrug (LA-GPE, 1) was synthesized as a new multifunctional drug candidate with antioxidant and neuroprotective properties for the treatment of neurodegenerative diseases. Physicochemical properties, chemical and enzymatic stabilities were evaluated, along with the capacity of LA-GPE to penetrate the blood-brain barrier (BBB) according to an in vitro parallel artificial membrane permeability assay for the BBB. We also investigated the potential effectiveness of LA-GPE against the cytotoxicity induced by 6-hydroxydopamine (6-OHDA) and H2O2 on the human neuroblastoma cell line SH-SY5Y by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Our results show that codrug 1 is stable at both pH 1.3 and 7.4, exhibits good lipophilicity (log P=1.51) and a pH-dependent permeability profile. Furthermore, LA-GPE was demonstrated to be significantly neuroprotective and to act as an antioxidant against H2O2- and 6-OHDA-induced neurotoxicity in SH-SY5Y cells.status: publishe

Lymphatic and blood vessels in scleroderma skin, a morphometric analysis

Vascular involvement is frequent in systemic sclerosis, but the role of the lymphatic vasculature is poorly known. Our aim was to evaluate lymphatic vessels in systemic sclerosis skin lesions. We studied skin forearm biopsies of 9 patients with systemic sclerosis and 7 age-matched controls. Lymphatic vessels were labeled with the monoclonal antibody D2-40 and blood vessels with a polyclonal antibody to von Willebrand Factor. All blood and lymphatic vessels present in each section were counted and total area, inner luminal area, and shape factors were measured. The number of blood and lymphatic vessels in papillary dermis was greater and their diameter lower than in reticular dermis both in systemic sclerosis and controls. In the reticular dermis, the number of lymphatic vessels was markedly reduced in systemic sclerosis (4.9 ± 1.1 μm−2 versus 8.9 ± 1.2 μm−2P = .03), and a similar trend was observed in papillary dermis (8.4 ± 3.7 μm−2 versus 8.1 ± 5.3 μm−2). Interestingly, the number of periglandular lymphatics in systemic sclerosis was not different from controls. The inner luminal area (possibly indicating compensatory dilation) of lymphatic vessels, particularly the periglandular ones, was greater in systemic sclerosis than in controls. No differences were observed in the number of blood vessels, but the percentage of blood vessel profiles (without lumen) was significantly less in systemic sclerosis both in papillary and in reticular dermis. In conclusion, our data show that skin lesions in systemic sclerosis are characterized by a selective rarefaction of lymphatic vasculature that spares periglandular vessels and that might have a pathogenic role in the evolution and in the clinical manifestations of the disease