Use of a high sensitive nanofluidic array for the detection of rare copies of BCR-ABL1 transcript in patients with Philadelphia-positiveacute lymphoblastic leukemia in complete responseIlaria

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Identification by High-Throughput Screening of Pseudomonas Acyl-Coenzyme A Synthetase Inhibitors

Pseudomonas infections are common among hospitalized, immunocompromised, and chronic lung disease patients. These infections are recalcitrant to common antibacterial therapies due to inherent antibiotic resistance. To meet the need of new anti- Pseudomonas drugs, a sensitive, homogenous, and robust assay was developed with the aim of identifying inhibitors of acyl-coenzyme A synthetases (ACSs) from Pseudomonas. Given the importance of fatty acids for in vivo nutrition of Pseudomonas, such inhibitors might have the potential to reduce the bacterial fitness during infection. The assay, based on a coupled reaction between the Pseudomonas spp. ACS and the firefly luciferase, allowed the identification of three classes of inhibitors by screening of a diverse compound collection. These compounds were confirmed to reversibly bind ACS with potencies in the micromolar range. Two classes were found to compete with acyl-coenzyme A, while the third one was competitive with fatty acid binding. Although these compounds inhibit the bacterial ACS in cell-free assays, they show modest or no effect on Pseudomonas growth in vitro

The Choice of Antithrombotic Therapy in a Patient with New-Onset Atrial Fibrillation and High Coronary Thrombotic Risk

Current guidelines are mandatory in the choice of anticoagulant and/or antiplatelet therapy in patients with atrial fibrillation undergoing percutaneous transluminal coronary angioplasty and in patients with coronary artery disease and previous percutaneous transluminal coronary angioplasty that develop atrial fibrillation. However, in the real world there are crossroads with multiple choices, especially taking into account patient's peculiar characteristics and risk factors, which sometimes are not well represented in the guidelines. The reported clinical case focuses on the choice of anticoagulation therapy in a patient with chronic and severe coronary artery disease and new diagnosis of atrial fibrillation who, considering his specifically high coronary thrombotic risk, probably should continue antiplatelet therapy

Discovery of 4-((1-(1H-imidazol-2-yl)alkoxy)methyl)pyridines as a new class of Trypanosoma cruzi growth inhibitors

The identification of a new series of growth inhibitors of Trypanosoma cruzi, the causative agent of Chagas' disease, is described. In vitro screening of a subset of compounds from our in-house compound collection against the parasite led to the identification of hit compound 1 with low micromolar inhibition of T. cruzi growth. SAR exploration on the hit compound led to the identification of compounds that show nanomolar parasite growth inhibition (T. cruzi EC; 50; ≤ 100 nM) and no cytotoxicity in human cells (HeLa CC; 50; > 50 μM). Further investigation identified CYP51 inhibition (compound 11 CYP51 IC; 50; 52 nM) as a possible mechanism of action of this new class of anti-parasitic agents

Earth observation for monitoring and mapping of cyanobacteria blooms. Case studies on five Italian lakes

Cyanobacterial blooms occur in many parts of the world as a result of entirely natural causes or human activity. Due to their negative effects on water resources, efforts are made to monitor cyanobacteria dynamics. This study discusses the contribution of remote sensing methods for mapping cyanobacterial blooms in lakes in northern Italy. Semi-empirical approaches were used to flag scum and cyanobacteria and spectral inversion of bio-optical models was adopted to retrieve chlorophyll-a (Chl-a) concentrations. Landsat-8 OLI data provided us both the spatial distribution of Chl-a concentrations in a small eutrophic lake and the patchy distribution of scum in Lake Como. ENVISAT MERIS time series collected from 2003 to 2011 enabled the identification of dates when cyanobacterial blooms affected water quality in three small meso-eutrophic lakes in the same region. On average, algal blooms occurred in the three lakes for about 5 days a year, typically in late summer and early autumn. A suite of hyperspectral sensors on air- and space-borne platforms was used to map Chl-a concentrations in the productive waters of the Mantua lakes, finding values in the range of 20 to 100 mgm-3. The present findings were obtained by applying state of the art of methods applied to remote sensing data. Further research will focus on improving the accuracy of cyanobacteria mapping and adapting the algorithms to the new-generation of satellite sensors.</p

Early decrease of oxidative stress by non-invasive ventilation in patients with acute respiratory failure

Oxidative stress plays an important role in chronic respiratory diseases where the use of non-invasive ventilation seems to reduce the oxidative damage. Data on acute respiratory failure are still lacking. The aim of the study is to investigate the interplay between oxidative stress and acute respiratory failure, and the role of non-invasive ventilation in this setting. We enrolled 60 patients suffering from acute respiratory failure (PaO2/FiO2 ratio &lt;300): 30 consecutive patients treated with non-invasive ventilation and 30 consecutive patients treated with conventional oxygen therapy. Serum levels of soluble Nox2-derived peptide (sNOX2-dp), a marker of NADPH-oxidase activation, and 8-iso-PGF2α and H2O2, markers of oxidative stress, were evaluated at baseline and after 3&nbsp;h of treatment. At baseline, higher values of sNOX2-dp, 8-iso-PGF2α and H2O2 are associated with lower values of PaO2/FiO2 ratio (p&nbsp;&lt;&nbsp;0.001). After 3&nbsp;h, serum levels of sNOX2-dp, H2O2, and 8-iso-PGF2α significantly decrease in patients treated with non-invasive ventilation, but not in patients treated with conventional oxygen therapy. Delta changes of oxidative stress parameters correlate inversely with the delta changes of PaO2/FiO2 (R&nbsp;=&nbsp;-0.623, p&nbsp;&lt;&nbsp;0.001 for sNOX2-dp; R&nbsp;=&nbsp;-0.428, p&nbsp;&lt;&nbsp;0.001 for H2O2; R&nbsp;=&nbsp;-0.548, p&nbsp;&lt;&nbsp;0.001 for 8-iso-PGF2α). In the acute respiratory failure setting, treatment with non-invasive ventilation reduces the levels of oxidative stress in the first hours. This reduction is associated with an improvement of PaO2/FiO2 ratio as well as in a reduction of NADPH-oxidase activity

Specific detection of cyanobacteria blooms in lakes through remote sensing: the approach of the project BLASCO (Blending Laboratory And Satellite Techniques For Detecting Cyanobacteria)

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Time to hospitalisation, CT pulmonary involvement and in-hospital death in COVID-19 patients in an Emergency Medicine Unit

Background: Patients with coronavirus disease 2019 (COVID- 19) are often treated at home given the limited healthcare resources. Many patients may have sudden clinical worsening and may be already compromised at hospitalisation. We investigated the burden of lung involvement according to the time to hospitalisation. Methods: In this observational cohort study, 55 consecutive COVID- 19- related pneu- monia patients were admitted to the Emergency Medicine Unit. Groups of lung in- volvement at computed tomography were classified as follows: 0 (75%). We also investigated in- hospital death and the predictive value of Yan- XGBoost model and PREDI- CO scores for death. Results: The median age was 74 years and 34 were men. Time to admission increased from 2 days in group 0 to 8.5- 9 days in groups 3 and 4. A progressive increase in LDH, CRP and d- dimer was found across groups, while a decrease of lymphocytes paO2/FiO2 ratio and SpO2 was found. Ten (18.2%) patients died during the in- hospital staying. Patients who died were older, with a trend to lower lymphocytes, a higher d- dimer, creatine phosphokinase and troponin T. The Yan- XGBoost model did not ac- curately predict in- hospital death with an AUC of 0.57 (95% confidence interval [CI] 0.37- 0.76), which improved after the addition of the lung involvement groups (AUC 0.68, 95%CI 0.45- 0.90). Conversely, a good predictive value was found for the origi- nal PREDI- CO score with an AUC of 0.76 (95% CI 0.58- 0.93) which remained similar after the addition of the lung involvement (AUC 0.76, 95% CI 0.57- 0.94). Conclusion: We found that delayed hospital admission is associated with higher lung involvement. Hence, our data suggest that patients at risk for more severe disease, such as those with high LDH, CRP and d- dimer, should be promptly referred to hos- pital care

Defecography: a still needful exam for evaluation of pelvic floor diseases

The aim of this discussion is to describe what is a defecography, how we have to perform it, what can we see and to present the main physio-pathological illnesses of pelvic floor and anorectal region that can be studied with this method and its advantages over other screening techniques. Defecography is a contrastographic radiological examination that highlights structural and functional pelvic floor diseases. Upon preliminary ileum-colic opacification giving to patient radiopaque contrast, are first acquired static images (at rest, in maximum voluntary contraction of the pelvic muscles, while straining) and secondarily dynamic sequences (during evacuation), allowing a complete evaluation of the functionality of the anorectal region and the pelvic floor. Defecography is an easy procedure to perform widely available, and economic, carried out in conditions where the patient experiences symptoms, the most realistic possible. It can be still considered reliable technology and first choice in many patients in whom the clinic alone is not sufficient and it is not possible or necessary to perform a study with MRI