Dexamethasone in acute cardiopulmonary syndrome with hyperinflammatory state

Abstract Introduction Elderly patient hospitalized due to acute heart failure often have a concomitant acute lung disease (acute bronchitis, pneumonia, chronic obstructive pulmonary disease-COPD- exacerbation). Establishing the role of each disease in a clinical picture of acute cardiopulmonary syndrome can be challenging. Procalcitonin has been used as a guide to antibiotic therapy with contrasting results. A common thread of these diseases is inflammation; a hyperinflammatory response determines more serious symptoms and a worse prognosis. Purpose We evaluated the effectiveness of a treatment with dexamethasone in patients with acute cardiopulmonary syndrome and a strong inflammatory response. Materials and methods We evaluated 157 consecutive HFPEF (heart failure with preserved ejection fraction) patients ≥80 years of age, with concomitant symptoms attributable to acute bronchitis, pneumonia, or COPD exacerbation, hospitalized due to worsening dyspnoea, with an NT-proBNP ≥3,000 pg/ml, and a finding X-ray of lung congestion with or without a consolidation. Reactive C Protein was measured. Patients with SARS-CoV-2, indication to corticosteroids use for other clinical conditions or need for mechanical ventilation were excluded. The 96 patients with values>20 mg/dl were randomized into 2 groups: 48 patients were treated open-label with dexamethasone at a dose of 8 mg iv/day for a maximun of ten days, in addition to the usual therapies for acute heart failure and lung disease, while the same number of patients were treated with the usual therapy. In both groups the antibiotic was administered only if the procalcitonin was≥0.25 μg/L. Clinical recovery time, length of hospitalization, in-hospital mortality, the need for a new hospitalization and mortality at one month were evaluated. Results The mean age of the patients was 88±4 years in the dexamethasone group and 87±5 in the usual therapy group. The results are shown in Table 1. Patients treated with dexamethasone experienced a faster clinical recovery and a shorter length of hospitalization. No significant differences were found regarding either in-hospital mortality or need for rehospitalization and mortality at 30 days. Conclusions Very elderly patients with acute cardiopulmonary syndrome and hyperinflammatory state associated with an excessive increase in Reactive Protein C have a favorable response to dexamethasone therapy in addition to the usual therapy in terms of clinical improvement and length of hospitalization. Our case history is small to evaluate a possible improvement in mortality. These findings need to be consolidated from double-blind randomized controlled trials Funding Acknowledgement Type of funding sources: None. Table

A stochastic approach to LCA of internal insulation solutions for historic buildings

Internal insulation is a typical renovation solution in historic buildings with valuable facades. However, it entails moisture-related risks, which affect the durability and life-cycle environmental performance. In this context, the EU project RIBuild developed a risk assessment method for both hygrothermal and life-cycle performance of internal insulation, to support decision-making. This paper presents the stochastic Life Cycle Assessment method developed, which couples the LCA model to a Monte-Carlo simulation, providing results expressed by probability distributions. It is applied to five insulation solutions, considering different uncertain input parameters and building heating scenarios. In addition, the influence of data variability and quality on the result is analyzed, by using input data from two sources: distributions derived from a generic Life Cycle Inventory database and "deterministic" data from Environmental Product Declarations. The outcomes highlight remarkable differences between the two datasets that lead to substantial variations on the systems performance ranking at the production stage. Looking at the life-cycle impact, the general trend of the output distributions is quite similar among simulation groups and insulation systems. Hence, while a ranking of the solutions based on a "deterministic" approach provides misleading information, the stochastic approach provides more realistic results in the context of decision-making

Proteomic and ionomic profiling reveals significant alterations of protein expression and calcium homeostasis in cystic fibrosis cells

Cystic fibrosis (CF) is an autosomal recessive disorder associated with mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and defective chloride transport across the epithelial cell membranes. Abnormal epithelial ion transport is the primary cause of persistent airway infections and chronic inflammation in CF patients. In order to gain further insight into the mechanisms of epithelial dysfunctions linked to CFTR mutations, we performed and integrated proteomic and ionomic analysis of human bronchial epithelial IB3-1 cells and compared them with a CFTR-complemented isogenic cell line (C38). Aside from changes that were consistent with known effects related to CFTR mutations, such as differences in glycolytic and gluconeogenic pathways and unfolded protein responses, differential proteomics highlighted significant alteration of protein expression and, in particular, of the 14-3-3 signalling pathway that is known to be involved in cellular calcium (Ca) homeostasis. Of note, restoring chloride efflux by acting on Ca cellular homeostasis has been shown to be a promising therapeutic intervention for CF. Ionomic analysis showed significant changes in the IB3-1 element profile compared with C38 cells and in particular we observed an increase of intracellular Ca that significantly correlates with intracellular zinc (Zn) levels, suggesting a synergistic role of Ca and Zn influx. This finding is particularly intriguing because Zn has been reported to be effective in CF treatment increasing Ca influx. Taken together, our proteomic and ionomic data reveal that CFTR mutation sets in motion endogenous mechanisms counteracting impaired chloride transport mainly acting on epithelial ion transport and increasing intracellular Ca, suggesting potential links between protein expression and this response

VLBI studies of DAGN and SMBHB hosting galaxies

Dual active galactic nuclei (DAGN) and supermassive black hole binaries (SMBHBs) at kpc and pc-scale separations, respectively, are expected during stages of galaxy merger and evolution. Their observational identification can address a range of areas of current astrophysics frontiers including the final parsec problem and their contribution towards the emission of low-frequency gravitational waves. This has however been difficult to achieve with current spectroscopy and time domain strategies. Very long baseline interferometry (VLBI) as a method of directly imaging radio structures with milli-arcsecond (mas) and sub-mas resolutions is introduced as a possible means of detecting DAGN and SMBHBs. We motivate its usage with expected observational signatures and cite some studies from literature to illustrate its current status, and present an updated list of candidates imaged with high-resolution radio observations. We then recall some shortcomings of the method with possible solutions and discuss future directions, relevant to large surveys with the upcoming Square Kilometer Array and future space VLBI missions.Comment: 13 pages, 2 table; Radio Science (accepted

timed flat infusion tfi 5 fluorouracil with irinotecan and oxaliplatin in pancreatic adenocarcinomas a single institution experience with fir fox regimen

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Deep-Manager: a versatile tool for optimal feature selection in live-cell imaging analysis

One of the major problems in bioimaging, often highly underestimated, is whether features extracted for a discrimination or regression task will remain valid for a broader set of similar experiments or in the presence of unpredictable perturbations during the image acquisition process. Such an issue is even more important when it is addressed in the context of deep learning features due to the lack of a priori known relationship between the black-box descriptors (deep features) and the phenotypic properties of the biological entities under study. In this regard, the widespread use of descriptors, such as those coming from pre-trained Convolutional Neural Networks (CNNs), is hindered by the fact that they are devoid of apparent physical meaning and strongly subjected to unspecific biases, i.e., features that do not depend on the cell phenotypes, but rather on acquisition artifacts, such as brightness or texture changes, focus shifts, autofluorescence or photobleaching. The proposed Deep-Manager software platform offers the possibility to efficiently select those features having lower sensitivity to unspecific disturbances and, at the same time, a high discriminating power. Deep-Manager can be used in the context of both handcrafted and deep features. The unprecedented performances of the method are proven using five different case studies, ranging from selecting handcrafted green fluorescence protein intensity features in chemotherapy-related breast cancer cell death investigation to addressing problems related to the context of Deep Transfer Learning. Deep-Manager, freely available at https://github.com/BEEuniroma2/Deep-Manager, is suitable for use in many fields of bioimaging and is conceived to be constantly upgraded with novel image acquisition perturbations and modalities

Chandra Observations of Candidate Subparsec Binary Supermassive Black Holes

We present analysis of Chandra X-ray observations of seven quasars that were identified as candidate subparsec binary supermassive black hole (SMBH) systems in the Catalina Real-Time Transient Survey based on the apparent periodicity in their optical light curves. Simulations predict that close-separation accreting SMBH binaries will have different X-ray spectra than single accreting SMBHs, including harder or softer X-ray spectra, ripple-like profiles in the Fe K-α line, and distinct peaks in the spectrum due to the separation of the accretion disk into a circumbinary disk and mini disks around each SMBH. We obtained Chandra observations to test these models and assess whether these quasars could contain binary SMBHs. We instead find that the quasar spectra are all well fit by simple absorbed power-law models, with the rest-frame 2–10 keV photon indices, Γ, and the X-ray-to-optical power slopes, α_(OX), indistinguishable from those of the larger quasar population. This may indicate that these seven quasars are not truly subparsec binary SMBH systems, or it may simply reflect that our sample size was too small to robustly detect any differences. Alternatively, the X-ray spectral changes might only be evident at energies higher than probed by Chandra. Given the available models and current data, no firm conclusions are drawn. These observations will help motivate and direct further work on theoretical models of binary SMBH systems, such as modeling systems with thinner accretion disks and larger binary separations