Pulmonary alveolar proteinosis (PAP) is a rare, diffuse lung disease characterized by accumulation of lipoprotein in lung surfactant in the alveolar space and terminal bronchioles, leading to impaired gas exchange and arterial hypoxemia. We present the case of a 51-year-old woman who was admitted with a diagnosis of severe SARS-CoV-2 pneumonia. Her condition did not improve with corticosteroids. A chest CT scan revealed ground-glass opacities in all lung lobes, with septal thickening. A differential diagnosis was proposed with other diseases. Bronchoscopy revealed milky bronchoalveolar lavage fluid, and staining with periodic acid-Schiff was positive, thus indicating PAP. Therefore, the patient underwent whole lung lavage, which led to clinical, radiological, and functional improvement. In the context of the COVID-19 pandemic, differential diagnosis ensures that appropriate attention is given to less prevalent entities such as PAP.
Gain suppression induced by excess carriers in Low Gain Avalanche Detectors (LGADs) has been investigated using 3 MeV protons in a nuclear microprobe. In order to modify the ionization density inside the detector, Ion Beam Induced Current (IBIC) measurements were performed at different proton beam incidence angles between 0° and 85°. The experimental results have been analyzed as a function of the ionization density projected on the multiplication layer, finding that the increase of ionization density leads to greater gain suppression. For bias voltages close to the gain onset value, this decrease in gain results into a significant distortion of the transient current waveforms measured by the Time-Resolved IBIC (TRIBIC) technique due to a deficit in the secondary holes component. For angles of incidence such that the Bragg peak falls within the sensitive volume of the detector, the formation of microplasmas modifies the behavior of the gain curves, producing an abrupt decrease in gain as the angle increases.
Lysosomes, the acidic degradation compartments of eukaryotic cells, play an essential role in many physiological processes. Their dysfunction is associated with a number of diseases, which are often related to an altered localization or luminal pH. Thus, the in-depth characterization of lysosomes within the intact eukaryotic cell is of utmost interest. For microscopic evaluation of lysosomal distribution and acidity, a number of labels have been developed, but many showed poor organelle specificity or rapid clearing from lysosomes, rendering them unsuitable for long-term observations. Here, we describe the synthesis and spectroscopic properties of a novel small molecule marker for lysosomes based on naphthalene monoimide with reversible, pH-dependent spectral shifts in both the absorption and the emission spectrum and acidity-associated changes in fluorescence lifetime. The dye can be excited either with single- or two-photon excitation and appears to be very stably associated with lysosomes for several days. We used this chromophore to detect chemically-induced changes of lysosomal pH in HeLa cells by ratiometric and FLIM imaging.
Fluorescent Dyes/analysis , Lysosomes/chemistry , Molecular Imaging/methods , Naphthalenes/analysis , Time-Lapse Imaging/methods , Fluorescent Dyes/metabolism , HeLa Cells , Humans , Hydrogen-Ion Concentration , Lysosomes/metabolism , Microscopy, Fluorescence/methods , Naphthalenes/metabolism
Introduction: Non-invasive respiratory therapies (NRT) were widely used in the first wave of the COVID-19 pandemic in different settings, depending on availability. The objective of our study was to present 90-day survival and associated factors in patients treated with NRT in a tertiary hospital without an Intermediate Respiratory Care Unit. The secondary objective was to compare the outcomes of the different therapies. Methods: Observational study of patients treated with NRT outside of an intensive care or intermediate respiratory care unit setting, diagnosed with COVID-19 and acute respiratory distress syndrome by radiological criteria and SpO2/FiO2 ratio. A multivariate logistic regression model was developed to determine independently associated variables, and the outcomes of high flow nasal cannula and continuous positive airway pressure were compared. Results: In total, 107 patients were treated and 85 (79.4%) survived at 90 days. Before starting NRT, the mean SpO2/FiO2 ratio was 119.8 ± 59.4. A higher SOFA score was significantly associated with mortality (OR 2,09; 95% CI 1.34-3.27), while self-pronation was a protective factor (OR 0.23; 95% CI 0.06-0.91). High flow nasal cannula was used in 63 subjects (58.9%), and continuous positive airway pressure in 41 (38.3%), with no differences between them. Conclusion: Approximately 4 out of 5 patients treated with NRT survived to 90 days, and no significant differences were found between high flow nasal cannula and continuous positive airway pressure.
Proton therapy has gained interest in recent years due to its excellent clinical outcomes. However, the lack of accurate biological data, especially in the Bragg peak region of clinical beams, makes it difficult to implement biophysically optimized treatment plans in clinical practice. In this context, low energy proton accelerator facilities provide the perfect environment to collect good radiobiological data, as they can produce high LET beams with narrow energy distributions. This study presents the radiobiology beam line that has been designed at the 18 MeV proton cyclotron facility at the National Centre of Accelerators (CNA, Seville, Spain), to perform irradiations of mono-layer cell cultures. To ensure that all the cells receive the same dose with a suitable dose rate, low beam intensities and broad and homogeneous beam profiles are necessary. To do so, at the CNA an unfocused beam has been used, broadened with a 500 µm thick aluminium scattering foil. Homogeneous dose profiles, with deviations lower than 10% have been obtained over a circular surface of 35 mm diameter for an incident average energy of 12.8 MeV. Further, a Monte Carlo simulation of the beam line has been developed with Geant4, and benchmarked towards experimental measurements, with differences generally below 1%. Once validated, the code has been used, together with an ionization chamber, for dosimetry studies, to characterize the beam and monitor the dose. Finally, cultures of Human Bone Osteosarcoma cells (U2OS) have been successfully irradiated at the radiobiology beam line, investigating the effects of radiation in terms of DNA damage induction.
Cyclotrons , Proton Therapy/instrumentation , Radiobiology , Monte Carlo Method , Radiometry
BACKGROUND: Bronchial thermoplasty (BT) is a minimally invasive procedure consisting of application of thermal energy into the airways to produce ablation of the hypertrophic smooth muscle. It was approved for use in moderate-severe asthma in Spain in 2010. OBJECTIVES: The aims of the present study are to analyze the effectiveness and the safety of BT in clinical practice in our center. METHODS: Participants had a confirmed diagnosis of severe asthma and poor control without therapeutic alternative. Effectiveness was measured by comparing exacerbations, admissions rates, asthma control, and medication 1 year prior and 1 year after BT was completed. All complications appearing during the procedure and in the first year were recorded. RESULTS: Patients had a mean age of 51 (SD 8) years and were predominantly female (17/23). The average number of activations per patient was 147 (16). The number of severe exacerbations was reduced by 75% (p < 0.001). A 38% reduction in admissions per year was also observed (p = 0.03). The Asthma Control Test improved by 7.1 (3.7) points (p = 0.018). Before BT, the dose of inhaled corticosteroids was 1,621 (1,015) µg of budesonide-equivalent and the dose of oral corticosteroids was 15 (13) mg of prednisone-equivalent. There was a reduction in 430 (731) µg of budesonide-equivalent (p = 0.02) and 4 (11) mg of prednisone (p = 0.094). No changes in lung function were observed. Complications were related mostly to exacerbation of asthma in the days following the procedure. CONCLUSIONS: BT is effective and safe for severe uncontrolled bronchial asthma in real clinical practice.
