Summary
Aims
Chronic obstructive pulmonary disease (COPD) is usually a progressive condition. Undiagnosed early‐stage disease, particularly in symptomatic patients, is likely to become more severe ...with time. Hence, prevention or reduction in disease progression is highly relevant. We evaluated the published data and discussed the potential impact of early intervention on the course of COPD.
Methods
We performed PubMed searches of studies in early or mild COPD, focusing on those relating to lung function decline.
Results
Smoking cessation reduced lung function decline at all stages of COPD, and the earlier the intervention, the greater the impact on lung function. Accumulating data from placebo‐controlled trials suggested that long‐acting bronchodilators can slow the decline in lung function, as well as reduce exacerbation and mortality rates and improve health‐related quality of life (HRQoL) in patients with mild‐to‐moderate COPD. Inhaled corticosteroids (ICS) do not impact lung function in early COPD, and further research is needed on the role of long‐acting β2‐agonist‐ICS combination therapy in these patients.
Conclusions
Initiating treatment early in the course of COPD is likely to slow disease progression and improve HRQoL. Current data support maintenance treatment with a long‐acting bronchodilator in this patient group. However, many questions remain unanswered regarding the optimal treatment of mild COPD, and further research is required to develop evidence‐based recommendations in this field.
Recently, two "fixed triple" single-inhaler combinations of an inhaled corticosteroid (ICS), a long-acting β
-agonist (LABA), and a long-acting muscarinic antagonist (LAMA) have become available for ...patients with COPD. This review presents the clinical evidence that led to the approval of these triple therapies, discusses the role of ICS in patients with COPD, and presents data on the relative efficacy of "fixed triple" (ICS/LAMA/LABA) therapy vs LAMA, ICS/LABA, and LAMA/LABA combinations, and summarizes studies in which ICS/LABAs were combined with LAMAs to form "open triple" combinations. Of the five main fixed triple studies completed so far, three evaluated the efficacy and safety of an extrafine formulation of beclometasone dipropionate, formoterol fumarate, and glycopyrronium; the other two studies evaluated fluticasone furoate, vilanterol, and umeclidinium. Overall, compared to LAMA, ICS/LABA, or LAMA/LABA, triple therapy decreased the risk of exacerbations and improved lung function and health status, with a favorable benefit-to-harm ratio. Furthermore, triple therapy showed a promising signal in terms of improved survival. The evidence suggests that triple therapy is the most effective treatment in moderate/severe symptomatic patients with COPD at risk of exacerbations, with marginal if any risk of side effects including pneumonia. Ongoing studies are examining the role of triple therapy in less severe symptomatic patients with COPD and asthma-COPD overlap.
•Al-Si/Mg2Si in-situ composite were fabricated by FSP at solid state.•Modification of Al-Si cast structure with uniform distribution of Mg2Si particles.•Formation of Mg2Si at the expense of Si ...particles can increase the Hardness.
Al/Mg2Si in-situ cast composites are very popular in Al casting industries, but they suffer low toughness due to very coarse Mg2Si particles. The friction stir processing (FSP) method can produce composites with very fine and uniform distribution of the reinforcement phase. Hence, in the present research, for the first time, FSP was used to fabricate Al/Mg2Si in-situ composites. For this purpose, pure Mg was added to Al-Si cast eutectic alloy by FSP. The formation of Mg2Si was studied by a variety of analysis techniques. The results prove the applicability of FSP for producing of Al/Mg2Si composite. The hardness of the prepared composite shows moderate improvement (~15%) compared to the FSPed base alloy.
Background
Asthma and other Th2 inflammatory conditions have been associated with increased susceptibility to viral infections. The mechanisms by which Th2 cytokines can influence immune responses to ...infections are largely unknown.
Methods
We measured the effects of Th2 cytokines (IL‐4 and IL‐13) on bronchial epithelial cell innate immune antiviral responses by assessing interferon (IFN‐β and IFN‐λ1) induction following rhinovirus (RV)‐16 infection. We also investigated the modulatory effects of Th2 cytokines on Toll‐like receptor 3 (TLR3), interferon‐responsive factor 3 (IRF3) and nuclear factor (NF)‐kB, that is key molecules and transcription factors involved in the rhinovirus‐induced interferon production and inflammatory cascade. Pharmacological and redox modulation of these pathways was also assessed.
Results
Th2 cytokines impaired RV‐16‐induced interferon production, increased rhinovirus replication and impaired TLR3 expression in bronchial epithelial cells. These results were replicated in vivo: we found increased IL‐4 mRNA levels in nasal epithelial cells from nasal brushing of atopic rhinitis patients and a parallel reduction in TLR3 expression and increased RV‐16 replication compared to nonatopic subjects. Mechanistically, Th2 cytokines impaired RV‐16‐induced activation of IRF3, but had no effects on RV‐16‐induced NF‐kB activation in bronchial epithelial cell cultures. N‐acetylcysteine and phosphoinositide 3‐kinase (PI3K) inhibitor restored the inhibitory effects of Th2 cytokines over RV‐16‐induced activation of IRF3.
Conclusions
IL‐4 and IL‐13, through inhibition of TLR3 expression and signalling (IRF3), impair immune response to RV‐16 infection. These data suggest that Th2 conditions increase susceptibility to infections and identify pharmacological approaches with potential to restore impaired immune response in these conditions.
Calverley PMA, Papi A, Page C, et al. 2022;17:1909-1920. The authors wish to correct Figure 1 on page 1912 after it came to their attention an error had been made in the second box of the last row ...(moderate-to-severe exacerbations), the correct number is 7 not 36. The corrected Figure 1 is shown below: The authors affirm that this error does not affect the results, discussion, and conclusions of the reported study and apologize for any inconvenience caused to the readers.
The integrated low-level trigger and data acquisition (TDAQ) system of the NA62 experiment at CERN is described. The requirements of a large and fast data reduction in a high-rate environment for a ...medium-scale, distributed ensemble of many different sub-detectors led to the concept of a fully digital integrated system with good scaling capabilities. The NA62 TDAQ system is rather unique in allowing full flexibility on this scale, allowing in principle any information available from the detector to be used for triggering. The design concept, implementation and performances from the first years of running are illustrated.
Abstract Randomized Controlled Trials (RCTs) are the “gold standard” for evaluating treatment outcomes providing information on treatments “efficacy”. They are designed to test a therapeutic ...hypothesis under optimal setting in the absence of confounding factors. For this reason they have high internal validity. The strict and controlled conditions in which they are conducted, leads to low generalizability because they are performed in conditions very different from real life usual care. Conversely, real life studies inform on the “effectiveness” of a treatment, that is, the measure of the extent to which an intervention does what is intended to do in routine circumstances. At variance to RCTs, real life trials have high generalizability, but low internal validity. Recently the number of real life studies has been rapidly growing in different areas of respiratory medicine, particularly in asthma and COPD. The role of such studies is becoming a hot topic in respiratory medicine, attracting research interest and debate. In the first part of this review we discuss some of the advantages and disadvantages of different types of RCTs and analyze the strengths and weaknesses of real life trials, considering the recent examples of some studies conducted in COPD. We then discuss methodological approaches and options to overcome some of the limitations of real life studies. Comparing the conclusions of effectiveness and efficacy trials can provide important pieces of information. Indeed, these approaches can result complementary, and they can guide the interpretation of each other results.
In the present work, we report an innovative approach for immunosensors construction. The experimental strategy is based on the anchoring of biological material at screen-printed carbon electrode ...(SPE) modified with electrodeposited Graphene Quantum Dots (GQD) and polyhydroxybutyric acid (PHB). It was used as functional substract basis for the recognition site receptor-binding domain (RBD) from coronavirus spike protein (SARS-CoV-2), for the detection of Anti-S antibodies (AbS). SEM images and EDS spectra suggest an interaction of the protein with GQD-PHB sites at the electrode surface. Differential pulse voltametric (DPV) measurements were performed before and after incubation, in presence of the target, shown a decrease in voltametric signal of an electrochemical probe (Fe(CN)63/4-). Using the optimal experimental conditions, analytical curves were performed in PBS and human serum spiked with AbS showing a slight matrix effect and a relationship between voltametric signal and AbS concentration in the range of 100 ng mL−1 and 10 μg mL−1. The selectivity of the proposed sensor was tested against yellow fever antibodies (YF) and the selective layer on the electrode surface did not interact with these unspecific antibodies. Eight samples of blood serum were analyzed and 87.5% of these total investigated provided adequate results. In addition, the present approach showed better results against traditional EDC/NHS reaction with enhancements in time and the possibility to develop an immunosensor in a single drop, since the proteins can be anchored prior to the electrode modification step.
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•An innovative approach for immunosensors construction based on the anchoring of biological material at screen-printed carbon electrode (SPE) modified.•Graphene Quantum Dots (GQD) and polyhydroxybutyric acid (PHB) as functional surface to anchor the recognition site receptor-binding domain (RBD).•Successfully detection of Anti-S antibodies (AbS) in human serum samples.•Feasible strategy for construction of immunosensor by exploring a single-step.
We investigated the anticancer effect of EGCG treatment on a breast carcinoma cell line resistant to tamoxifen (MCF-7Tam cells). As there are no reports about the molecular mechanisms implicated in ...EGCG treatment of tamoxifen resistant breast carcinoma cells, we studied the effects of EGCG treatment on three plasma membrane proteins that are involved in the mechanism of drug-resistance: Multidrug Resistance Protein (MRP1), P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). EGCG treatment (10-100
μg/ml for 24-72
hours) caused cell growth inhibition and dose-dependent apoptosis: after 100
μg/ml EGCG treatment for 24
hours, Bax expression increased and Bcl2 expression decreased (p<0.05). Coherently, Annexin V-FITC apoptosis assay detected a significant increase in labelled cells (p<0.05). EGCG did not affect MRP1: in contrast, 100
μg/ml EGCG administration caused P-gp decrease to 53% of control cells (p<0.001) and this effect was not due to downregulation of P-gp gene expression. EGCG induced P-gp decrease even when MG132, a strong proteasome inhibitor, was given together with EGCG to MCF-7Tam cells. EGCG treatment also inhibited BCRP activity: mRNA transcription and protein level did not change after treatment, but mitoxantrone test demonstrated a strong inhibition of BCRP activity (p<0.001). In conclusion, the present results showed that EGCG could down-regulate the activity of two molecules that play a key role in drug metabolism and transport and that are highly expressed in tamoxifen resistant breast carcinoma cells. The interaction of EGCG and drugs used in the therapy of estrogen sensitive breast carcinoma ought to be subject of studies and the potential use of EGCG in drug-resistant diseases ought to be better considered.
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