Evaluation of radiological and pathological prognostic factors in surgically-treated patients with bronchoalveolar carcinoma

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Fluorescence lifetime microscopy unveils the supramolecular organization of liposomal Doxorubicin

The supramolecular organization of Doxorubicin (DOX) within the standard Doxoves® liposomal formulation (DOX®) is investigated using visible light and phasor approach to fluorescence lifetime imaging (phasor-FLIM). First, the phasor-FLIM signature of DOX® is resolved into the contribution of three co-existing fluorescent species, each with its characteristic mono-exponential lifetime, namely: crystallized DOX (DOXc, 0.2 ns), free DOX (DOXf, 1.0 ns), and DOX bound to the liposomal membrane (DOXb, 4.5 ns). Then, the exact molar fractions of the three species are determined by combining phasor-FLIM with quantitative absorption/fluorescence spectroscopy on DOXc, DOXf, and DOXb pure standards. The final picture on DOX® comprises most of the drug in the crystallized form (∼98%), with the remaining fractions divided between free (∼1.4%) and membrane-bound drug (∼0.7%). Finally, phasor-FLIM in the presence of a DOX dynamic quencher allows us to suggest that DOXf is both encapsulated and non-encapsulated, and that DOXb is present on both liposome-membrane leaflets. We argue that the present experimental protocol can be applied to the investigation of the supramolecular organization of encapsulated luminescent drugs/molecules all the way from the production phase to their state within living matter

Assessing the physicochemical stability and intracellular trafficking of mRNA-based COVID-19 vaccines

: The emergence of SARS-CoV-2 in Wuhan, China in 2019 has had a profound impact on humanity in every facet. While vaccines against this viral pathogen have been approved a year later, limitations to this therapeutic intervention persist, such as drug sensitivity to transportation and storage conditions, as well as significant financial losses from non-injected resuspended vials. Our research delves into the effects of thermal denaturation (4 - 40 °C) and light irradiation (720 and 10460 kJ/m2) on the mRNA-based vaccines BNT162b2 from BioNTech/Pfizer and mRNA-1273 from Moderna. We also investigated vaccine stability following incubation in syringes to simulate potential interactions with silicon oil. By assaying the effects of these stressors via biochemical and biophysical methods, we aim to elucidate the physicochemical properties, integrity, and stability of these mRNA-based vaccines. Furthermore, the incorporation of a fluorophore into both vaccines allowed us to monitor their localization within cells and assess their capacity to evade vesicular transport mechanisms, thus evaluating the differences between the two formulations. A comprehensive understanding of the aforementioned attributes can enable the establishment of optimal storage and manipulation conditions for these vaccines, thereby ensuring their safe and efficacious application while minimizing the waste of functional and safe therapeutic agents

Short-Term Repeatability of Noninvasive Aortic Pulse Wave Velocity Assessment: Comparison between Methods and Devices

BACKGROUND Aortic pulse wave velocity (PWV) is an indirect index of arterial stiffness and an independent cardiovascular risk factor. Consistency of PWV assessment over time is thus an essential feature for its clinical application. However, studies providing a comparative estimate of the reproducibility of PWV across different noninvasive devices are lacking, especially in the elderly and in individuals at high cardiovascular risk. METHODS Aimed at filling this gap, short-term repeatability of PWV, estimated with 6 different devices (Complior Analyse, PulsePen-ETT, PulsePen-ET, SphygmoCor Px/Vx, BPLab, and Mobil-O-Graph), was evaluated in 102 high cardiovascular risk patients hospitalized for suspected coronary artery disease (72 males, 65 ± 13 years). PWV was measured in a single session twice, at 15-minute interval, and its reproducibility was assessed though coefficient of variation (CV), coefficient of repeatability, and intraclass correlation coefficient. RESULTS The CV of PWV, measured with any of these devices, was <10%. Repeatability was higher with cuff-based methods (BPLab: CV = 5.5% and Mobil-O-Graph: CV = 3.4%) than with devices measuring carotid-femoral PWV (Complior: CV = 8.2%; PulsePen-TT: CV = 8.0%; PulsePen-ETT: CV = 5.8%; and SphygmoCor: CV = 9.5%). In the latter group, PWV repeatability was lower in subjects with higher carotid-femoral PWV. The differences in PWV between repeated measurements, except for the Mobil-O-Graph, did not depend on short-term variations of mean blood pressure or heart rate. CONCLUSIONS Our study shows that the short-term repeatability of PWV measures is good but not homogenous across different devices and at different PWV values. These findings, obtained in patients at high cardiovascular risk, may be relevant when evaluating the prognostic importance of PW

Comparison Between Invasive and Noninvasive Methods to Estimate Subendocardial Oxygen Supply and Demand Imbalance

Background Estimation of the balance between subendocardial oxygen supply and demand could be a useful parameter to assess the risk of myocardial ischemia. Evaluation of the subendocardial viability ratio (SEVR, also known as Buckberg index) by invasive recording of left ventricular and aortic pressure curves represents a valid method to estimate the degree of myocardial perfusion relative to left ventricular workload. However, routine clinical use of this parameter requires its noninvasive estimation and the demonstration of its reliability. Methods and Results Arterial applanation tonometry allows a noninvasive estimation of SEVR as the ratio of the areas directly beneath the central aortic pressure curves obtained during diastole (myocardial oxygen supply) and during systole (myocardial oxygen demand). However, this "traditional" method does not account for the intra-ventricular diastolic pressure and proper allocation to systole and diastole of left ventricular isometric contraction and relaxation, respectively, resulting in an overestimation of the SEVR values. These issues are considered in the novel method for SEVR assessment tested in this study. SEVR values estimated with carotid tonometry by "traditional" and "new" method were compared with those evaluated invasively by cardiac catheterization. The "traditional" method provided significantly higher SEVR values than the reference invasive SEVR: average of differences +/- SD= 44 +/- 11% (limits of agreement: 23% - 65%). The noninvasive "new" method showed a much better agreement with the invasive determination of SEVR: average of differences +/- SD= 0 +/- 8% (limits of agreement: -15% to 16%). Conclusions Carotid applanation tonometry provides valid noninvasive SEVR values only when all the main factors determining myocardial supply and demand flow are considered

Metal Abundances of Red Clump Stars in Open Clusters: I. NGC 6819

We present an analysis of high dispersion spectra (R~40000) of three red clump stars in the old open cluster NGC 6819. The spectra were obtained with SARG, the high dispersion spectrograph of the Telescopio Nazionale Galileo. The spectra were analyzed using both equivalent widths measured with an automatic procedure, and comparisons with synthetic spectra. NGC 6819 is found to be slightly metal-rich ([Fe/H]= +0.09 +/-0.03, internal error); there are no previous high resolution studies to compare with. Most element-to-element abundance ratios are close to solar; we find a slight excess of Si, and a significant Na overabundance. Our spectra can also be used to derive the interstellar reddening towards the cluster, by comparing the observed colours with those expected from line excitation: we derive E(B-V)=0.14 +/-0.04, in agreement with the most recent estimate for this cluster.Comment: 30 pages, 4 encapsulated figures, uses aastex, AJ in pres

Dwarf Elliptical Galaxies: Structure, Star Formation, and Color-Magnitude Diagrams

The aim of this paper is to cast light on the formation and evolution of elliptical galaxies by means of N-body/hydro-dynamical simulations that include star formation, feed-back and chemical evolution. Particular attention is paid to the case of dwarf spheroidals of the Local Group which, thanks to their proximity and modern ground-based and space instrumentation, can be resolved into single stars so that independent determinations of their age and star formation history can be derived. Dwarf galaxies are known to exhibit complicated histories of star formation ranging from a single very old episode to a series of bursts over most of the Hubble time. We start from virialized haloes of dark matter, and follow the infall of gas into the potential wells and the formation of stars. We find that in objects of the same total mass, different star formation histories are possible, if the collapse phase started at different initial densities. We predict the final structure of dwarf spheroidal galaxies, their kinematics, their large scale distribution of gas and stars, and their detailed histories of the star formation and metal enrichment. Using a population synthesis technique, star formation and metal enrichment rates are then adopted to generate the present color-magnitude diagrams of the stellar populations hosted by dwarf spheroidal galaxies. varying the cosmological parameters $H_0$ and $q_0$. compared with the observational ones for some dwarf spheroidals of the Local Group.Comment: 12 pages, 11 figures, accepted for publication in MNRAS, figs 1,8,9,10 and 11 in jpeg forma

Whole Lung Irradiation after High-Dose Busulfan/Melphalan in Ewing Sarcoma with Lung Metastases: An Italian Sarcoma Group and Associazione Italiana Ematologia Oncologia Pediatrica Joint Study

SIMPLE SUMMARY: The lung is the most frequent site of metastasis in Ewing sarcoma, the second most common bone cancer affecting children, adolescents and young adults. The five-year overall survival of patients with isolated lung metastasis is approximately 50% after multimodal treatments including chemotherapy, surgery and radiotherapy. This retrospective study aimed to investigate the feasibility and the predictors of survival in 68 Ewing sarcoma patients with lung metastases who received high-dose chemotherapy with busulfan and melphalan, followed by reduced dose whole-lung irradiation, as part of two prospective and consecutive treatment protocols. This combined treatment strategy is feasible and might contribute to the disease control in lung metastatic Ewing sarcoma with responsive disease. Furthermore, the results of this study provide support to explore the treatment stratification for lung metastatic Ewing sarcoma based on the histological response of the primary tumor. ABSTRACT: Purpose: To analyze toxicity and outcome predictors in Ewing sarcoma patients with lung metastases treated with busulfan and melphalan (BU-MEL) followed by whole-lung irradiation (WLI). Methods: This retrospective study included 68 lung metastatic Ewing Sarcoma patients who underwent WLI after BU-MEL with autologous stem cell transplantation, as part of two prospective and consecutive treatment protocols. WLI 12 Gy for <14 years old and 15 Gy for ≥14 years old patients were applied at least eight weeks after BU-MEL. Toxicity, overall survival (OS), event-free survival (EFS) and pulmonary relapse-free survival (PRFS) were estimated and analyzed. Results: After WLI, grade 1–2 and grade 3 clinical toxicity was reported in 16.2% and 5.9% patients, respectively. The five-year OS, EFS and PRFS with 95% confidence interval (CI) were 69.8% (57.1–79.3), 61.2% (48.4–71.7) and 70.5% (56.3–80.8), respectively. Patients with good histological necrosis of the primary tumor after neoadjuvant chemotherapy showed a significant decreased risk of pulmonary relapse or death compared to patients with poor histological necrosis. Conclusions: WLI at recommended doses and time interval after BU-MEL is feasible and might contribute to the disease control in Ewing sarcoma with lung metastases and responsive disease. Further studies are needed to explore the treatment stratification based on the histological response of the primary tumor

Epidemiology and Microbiology of Skin and Soft Tissue Infections: Preliminary Results of a National Registry

Skin and soft tissue infections (SSTIs) represent a wide range of clinical conditions characterized by a considerable variety of clinical presentations and severity. Their aetiology can also vary, with numerous possible causative pathogens. While other authors previously published analyses on several types of SSTI and on restricted types of patients, we conducted a large nationwide surveillance programme on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients. Twenty-five Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. All the cases included in our database, independently from their severity, have been managed by ID specialists joining the study while SSTIs from other wards/clinics have been excluded from this analysis. Here, we report the preliminary results of our study, referring to a 12-month period (October 2016–September 2017). During this period, the study population included 254 adult patients and a total of 291 SSTI diagnoses were posed, with 36 patients presenting more than one SSTIs. The type of infection diagnosed, the aetiological micro-organisms involved and some notes on their antimicrobial susceptibilities were collected and are reported herein. The enrichment of our registry is ongoing, but these preliminary results suggest that further analysis could soon provide useful information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy

Stellar Population Astrophysics (SPA) with the TNG. Stock 2, a little-studied open cluster with an eMSTO

Stock 2 is a little-studied open cluster that shows an extended main-sequence turnoff (eMSTO). In order to investigate this phenomenon and characterise the cluster itself, we performed high-resolution spectroscopy in the framework of the Stellar Population Astrophysics project. We employed the High Accuracy Radial velocity Planet Searcher in the Northern hemisphere spectrograph at the Telescopio Nazionale Galileo (TNG). We completed our observations with additional spectra taken with the Catania Astrophysical Observatory Spectropolarimeter. We observed 46 stars (dwarfs and giants). They represent by far the largest sample collected for this cluster to date. We provide the stellar parameters, the extinction, and the radial and projected rotational velocities for most of the stars. Chemical abundances for 21 species with atomic numbers up to 56 have also been derived. We note a differential reddening in the cluster field with an average value of 0.27 mag. This appears the main cause for the observed eMSTO because it cannot be explained as the result of different rotational velocities, as found in other clusters. We estimate an age for Stock 2 of 450 ± 150 Ma, which corresponds to a MSTO stellar mass of ≈2.8 M⊙. The cluster mean radial velocity is about 8.0 km s−1. We find a solar-like metallicity for the cluster, [Fe/H] = −0.07 ± 0.06, compatible with its galactocentric distance. The chemical abundances of main-sequence stars and giants are compatible within the errors. The exceptions are barium and strontium, which are clearly overabundant in giants, and cobalt, which is only marginally overabundant. Finally, the chemical composition of Stock 2 is fully compatible with the composition observed in other open clusters of the Galactic thin-disc population. Based on observations made with the Italian Telescopio Nazionale Galileo (TNG) operated on the island of La Palma by the Fundación Galileo Galilei of the INAF (Istituto Nazionale di Astrofisica) at the Observatorio del Roque de los Muchachos. This study is part of the Large Program titled SPA - Stellar Population Astrophysics: the detailed, age-resolved chemistry of the Milky Way disk (PI: L. Origlia), granted observing time with HARPS-N and GIANO-B echelle spectrographs at the TNG