Real Time 3D echocardiography (RT3D) for assessment of ventricular and vascular function in hypertensive and heart failure patients

RT-3D echo allows a non invasive, comprehensive assessment of cardiac and systemic hemodynamics, offering insight access to key variables – such as increased systemic vascular resistances in hypertensives and reduced ventricular-arterial coupling in heart failure patients

Acute Coronary Syndromes: From The Laboratory Markers To The Coronary Vessels

A number of “interesting” risk markers have been proposed as providing prognostic informations in acute coronary syndromes (ACS). Elevation in plasma inflammatory and necrosis biomarkers have been related to future cardiovascular events in individuals with or without prior myocardial infarction. Recently BNP and pro-BNP are entered in clinical practice to recognize patients at major risk, providing incremental information respect to the traditional markers. Together with these laboratory indexes, a few of promising laboratory markers once easily available, could become usefull in identification of patients at high risk

Molecular-Based Reappraisal of a Historical Record of Dothistroma Needle Blight in the Centre of the Mediterranean Region

In this work, we rechecked, using species-specific Loop mediated isothermal AMPlification (LAMP) diagnostic assays followed by sequencing of fungal isolates at the beta-2-tubulin (tub2) gene region, a historical and never confirmed report of Dothistroma needle blight (DNB) in the introduced Monterey pine (Pinus radiata D. Don) in the mountains in the extreme tip of southern Italy. The report dates back to the mid-1970s, and predates the molecular-based taxonomic revision of the genus Dothistroma that defined the species accepted today. In the fall of 2019, symptomatic needles of Monterey pine and Corsican pine (Pinus nigra subsp. laricio (Poir.) Palib. ex Maire) were sampled in the area of the first finding. The applied diagnostic methods revealed the presence of Dothistroma septosporum (Dorogin) M. Morelet on both pine species. In this way, we: (i) confirmed the presence of the disease; (ii) clarified the taxonomic identity of the causal agent now occurring at that site; (iii) validated the species-specific LAMP diagnostic protocol we recently developed for Dothistroma for use on a portable field instrument, and (iv) showed that the pathogen now also attacks the native P. nigra subsp. laricio, a species particularly susceptible to the disease, indigenous to the mountains of Calabria, which is one of the very few areas where the species’ genetic resources are conserved. Comparative genetic analysis of the rare populations of D. septosporum found in the central Mediterranean region and in the native range of P. nigra subsp. laricio could help to clarify the history of the spread of the pathogen in southern Europe and better evaluate the risk it poses to the conservation of native pine species

Pulmonary arterial hypertension and interstitial lung fibrosis in systemic sclerosis: One-stop shop assessment with cardiac and chest ultrasound

Background: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are common complications of systemic sclerosis (SSc). Echocardiography evaluates PAH, and chest sonography detects even mild ILC as ultrasound lung comets (ULC), i.e. multiple comet-tails fanning out from the lung surface and originating from subpleural interlobular septa thickened by fibrosis. Aim: to assess ILD and PAH by integrated cardiac and chest ultrasound in SSc. Materials and methods: We enrolled 30 consecutive SSc patients (age=54?13 years, 23 females) in the Rheumatology Clinic of Pisa University. In all, we assessed Systolic Pulmonary Arterial Pressure (SPAP), from maximal velocity of tricuspid regurgitation flow, and ULC score with chest sonography (summing the number of ULC from each scanning space of anterior and posterior right and left chest, from second to fifth intercostal space). All patients underwent plasma assay for anti-topoisomerase antibodies (anti-Scl70), associated with development of pulmonary fibrosis. Twenty-eight patients also underwent High Resolution Computed Tomography, HRCT (from 0=no fibrosis to 3=honey combing). Results: ULC number - but not SPAP - was correlated to HRCT fibrosis and presence SSc-70 antibodies (see figure). ULC number was similar in localized or diffuse forms (16?20 vs. 21?19, p=ns) and was unrelated to SPAP (r=0.216, p=ns). Conclusions: Cardiac and chest sonography assessment of SPAP and ULC allow a complete, simple, radiation-free characterization of vascular and interstitial lung involvement in SSc - all in one setting and with the same instrument, same transducer and the same sonographer. In particular, ULC number, but not SPAP, is associated with HRCT evidence of lung fibrosis and presence of Scl-70 antibodies

A novel phage-library-selected peptide inhibits human TNF-α binding to its receptors

We report the identification of a new human tumor necrosis factor-alpha (TNF-α) specific peptide selected by competitive panning of a phage library. Competitive elution of phages was obtained using the monoclonal antibody adalimumab, which neutralizes pro-inflammatory processes caused by over-production of TNF-α in vivo, and is used to treat severe symptoms of rheumatoid arthritis. The selected peptide was synthesized in monomeric and branched form and analyzed for binding to TNF-α and competition with adalimumab and TNF-α receptors. Results of competition with TNF-α receptors in surface plasmon resonance and melanoma cells expressing both TNF receptors make the peptide a candidate compound for the development of a novel anti-TNF-α drug

Near-infrared quantum dots labelled with a tumor selective tetrabranched peptide for in vivo imaging

Near-infrared quantum dots (NIR QDs) are a new class of fluorescent labels with excellent bioimaging features, such as high fluorescence intensity, good fluorescence stability, sufficient electron density, and strong tissue-penetrating ability. For all such features, NIR QDs have great potential for early cancer diagnosis, in vivo tumor imaging and high resolution electron microscopy studies on cancer cells

Determination of volatile organic compounds in exhaled breath of heart failure patients by needle trap micro-extraction coupled with gas chromatography-tandem mass spectrometry

The analytical performances of needle trap micro-extraction (NTME) coupled with gas chromatography tandem mass spectrometry were evaluated by analyzing a mixture of twenty-two representative breath VOCs belonging to different chemical classes (i.e. hydrocarbons, ketones, aldehydes, aromatics and sulfurs). NTME is an emerging technique that guarantees detection limits in pptv range by pre-concentrating low volumes of sample, and it is particularly suitable for breath analysis. For most VOCs, detection limits between 20 and 500 pptv were obtained by pre-concentrating 25 mL of a humidified standard gas mixture at a flow rate of 15 mL/min. For all compounds, inter- and intra-day precisions were always below 15%, confirming the reliability of the method. The procedure was successfully applied to the analysis of exhaled breath samples collected from forty heart failure patients during their stay in the University Hospital of Pisa. The majority of patients (about 80%) showed a significant decrease of breath acetone levels (a factor of 3 or higher) at discharge compared to admission (acute phase) in correspondence to the improved clinical conditions during hospitalization, thus making this compound eligible as a biomarker of heart failure exacerbation

Coupling to a cancer-selective heparan-sulfate-targeted branched peptide can by-pass breast cancer cell resistance to methotrexate

Cancer-selective tetra-branched peptides, named NT4, can be coupled to different functional units for cancer cell imaging or therapy. NT4 peptides specifically bind to lipoprotein receptor-related proteins (LRP) receptors and to heparan sulfate chains on membrane proteoglycans and can be efficiently internalized by cancer cells expressing these membrane targets. Since binding and internalization of NT4 peptides is mediated by specific NT4 receptors on cancer cell membranes and this may allow drug resistance produced by drug membrane transporters to be by-passed, we tested the ability of drug-armed NT4 to by-pass drug resistance in cancer cell lines. We found that MTX-conjugated NT4 allows drug resistance to be by-passed in MTX-resistant human breast cancer cells lacking expression of folate reduced carrier. NT4 peptides appear to be extremely promising cancer-selective targeting agents that can be exploited as theranostics in personalized oncological applications

Antibacterial and Anti-Inflammatory Activity of Branched Peptides Derived from Natural Host Defense Sequences

Antibiotic resistance is a major global health threat, necessitating the development of new treatments and diverse molecules to combat severe infections and preserve the efficacy of existing drugs. Antimicrobial peptides (AMPs) offer a versatile arsenal against bacteria, and peptide structure branching can enhance their resistance to proteases and improve their overall efficacy. A small library of peptides derived from natural host defense peptides and synthesized in a tetrabranched form was selected against E. coli. Six selected branched peptides were further studied for antibacterial activity against a panel of strains, biofilm inhibition, protease resistance, and cytotoxicity. Their structure was predicted computationally and their mechanism of action was investigated by electron microscopy and by using fluorescent dyes. The peptide BAMP2 showed promise in a mouse skin infection model, indicating the potential for local infection treatment

Ultrasound lung comets in systemic sclerosis: a chest sonography hallmark of pulmonary interstitial fibrosis

Objective. To assess the correlation between ultrasound lung comets (ULCs, a recently described echographic sign of interstitial lung fibrosis) and the current undisputed gold-standard high-resolution CT (HRCT) to detect pulmonary fibrosis in patients with SSc. Methods. We enrolled 33 consecutive SSc patients (mean age 5413 years, 30 females) in the Rheumatology Clinic of the University of Pisa. We assessed ULCs and chest HRCT within 1 week independently in all the patients. ULC score was obtained by summing the number of lung comets on the anterior and posterior chest. Pulmonary fibrosis was quantified by HRCT with a previously described 30-point Warrick score. Results. Presence of ULCs (defined as a total number more than 10) was observed in 17 (51%) SSc patients. Mean ULC score was 3750, higher in the diffuse than in the limited form (7366 vs 2135; P<0.05). A significant positive linear correlation was found between ULCs and Warrick scores (r?0.72; P<0.001). Conclusions. ULCs are often found in SSc, are more frequent in the diffuse than the limited form and are reasonably well correlated with HRCT-derived assessment of lung fibrosis. They represent a simple, bedside, radiation-free hallmark of pulmonary fibrosis of potential diagnostic and prognostic value