Chronic Cough Patient Perspective: questionnaire validation and symptom impact.

Background: Chronic cough (CC) is underevaluated and underreported. The introduction of a tool that is easy to complete, score and interpret and with the psychometric properties requested for use in individual patients could improve clinical practice.

Objective: This cross-sectional study aimed to validate the Chronic Cough Patient Perspective (CCPP) for assessing CC in daily practice.

Activity of Membrane-Permeabilizing Lpt Peptides.

Herein, we investigated the toxicity and membrane-permeabilizing capabilities of Lpt and Lpt-like peptides, belonging to type I toxin-antitoxin systems carried by plasmid DNA of strains. These 29 amino acid peptides are predicted to form α-helical structures with a conserved central hydrophobic sequence and differently charged hydrophilic termini. Like Lpt, the expression of Lpt-like in induced growth arrest, nucleoid condensation, and cell membrane damage, suggesting membrane interaction as the mode of action.

Molecular Characterization of the Allergenic Arginine Kinase from the Edible Insect Hermetia illucens (Black Soldier Fly).

Scope: Arginine kinase (AK) is an important enzyme for energy metabolism of invertebrate cells by participating in the maintenance of constant levels of ATP. However, AK is also recognized as a major allergen in insects and crustaceans capable of cross-reactivity with sera of patients sensitized to orthologous proteins. In the perspective of introducing insects or their derivatives in the human diet in Western world, it is of primary importance to evaluate possible risks for allergic consumers.

3-O-Methyltolcapone and Its Lipophilic Analogues Are Potent Inhibitors of Transthyretin Amyloidogenesis with High Permeability and Low Toxicity.

Transthyretin (TTR) is an amyloidogenic homotetramer involved in the transport of thyroxine in blood and cerebrospinal fluid. To date, more than 130 TTR point mutations are known to destabilise the TTR tetramer, leading to its extracellular pathological aggregation accumulating in several organs, such as heart, peripheral and autonomic nerves, and leptomeninges. Tolcapone is an FDA-approved drug for Parkinson's disease that has been repurposed as a TTR stabiliser.

Clinical Characteristics and Outcomes of Patients with Acute Respiratory Failure Due to SARS-CoV-2 Interstitial Pneumonia Treated with CPAP in a Medical Intermediate Care Setting: A Retrospective Observational Study on Comparison of Four Waves.

Background: In COVID-19 patients non-invasive-positive-pressure-ventilation (NIPPV) has held a challenging role to reduce mortality and the need for invasive mechanical ventilation (IMV). The aim of this study was to compare the characteristics of patients admitted to a Medical Intermediate Care Unit for acute respiratory failure due to SARS-CoV-2 pneumonia throughout four pandemic waves.

Methods: The clinical data of 300 COVID-19 patients treated with continuous positive airway pressure (CPAP) were retrospectively analysed, from March-2020 to April-2022.

Severe asthma: One disease and multiple definitions.

Introduction: There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used.

Strategies to Investigate Membrane Damage, Nucleoid Condensation, and RNase Activity of Bacterial Toxin-Antitoxin Systems.

A large number of bacterial toxin-antitoxin (TA) systems have been identified so far and different experimental approaches have been explored to investigate their activity and regulation both in vivo and in vitro. Nonetheless, a common feature of these methods is represented by the difficulty in cell transformation, culturing, and stability of the transformants, due to the expression of highly toxic proteins. Recently, in dealing with the type I Lpt/RNAII and the type II YafQ/DinJ TA systems, we encountered several of these problems that urged us to optimize methodological strategies to study the phenotype of recombinant host cells.

Sprouting of Sorghum ( [L.] Moench): Effect of Drying Treatment on Protein and Starch Features.

The nutritional and physicochemical properties of sorghum proteins and starch make the use of this cereal for food production challenging. Sprouting is a cost-effective technology to improve the nutritional and functional profile of grains. Two drying treatments were used after sorghum sprouting to investigate whether the drying phase could improve the protein and starch functionalities.

Increasing dosages of low-molecular-weight heparin in hospitalized patients with Covid-19.

We conducted an observational cohort study in adult patients consecutively admitted for the respiratory illness Covid-19 to our hub hospital from March 9 to April 7, 2020. The high observed rate of venous thromboembolism prompted us to increase the prophylactic doses of enoxaparin from 40 mg daily up to 1 mg/kg twice daily in patients admitted to intensive care units (ICU), 0.7 mg/kg twice daily in high-intensity of care wards and 1 mg/kg daily in low-intensity of care wards.

Shotgun proteomics, in-silico evaluation and immunoblotting assays for allergenicity assessment of lesser mealworm, black soldier fly and their protein hydrolysates.

Since 2018, insects have belonged the category of Novel Foods and the presence of allergens represents one of the main hazards connected to their consumption, also due to the potential cross-reactivity with Arthropoda pan-allergens. In the present work, the allergenicity assessment of black soldier fly and lesser mealworm was performed with a shotgun bottom-up proteomic approach combined with in-silico assessment, followed by IgG- and IgE-immunoblotting experiments. The peptides identified, filtered for their abundance and robustness, belonged mainly to muscle proteins, which represented the most abundant protein group.

Evolving phenotypes to endotypes: is precision medicine achievable in asthma?

: The development of biologic molecules led to a drastic change in the therapeutic approach to asthma. With the prospect of acting on different pathophysiological mechanisms of the disease, the idea of precision medicine was developed, in which a single molecule is able to modify a specific triggering mechanism. Thus, it seemed limiting to stop at the distinction of patients phenotypes and the concept of endotypes became more relevant in the therapeutic approach.

Functional characterization of the type I toxin Lpt from Lactobacillus rhamnosus by fluorescence and atomic force microscopy.

Lpt is a 29 amino acid long type I toxin identified in the plasmid DNA of wild Lactobacillus rhamnosus strains isolated from food. We previously reported that transcription of the encoding gene was upregulated under nutritional starvation conditions mimicking cheese ripening environment. The heterologous expression of the Lpt peptide in E.

Expression of DinJ-YafQ System of Group Strains in Response to Food Processing Stresses.

Toxin-antitoxin (TA) systems are widely distributed in bacterial genomes and are involved in the adaptive response of microorganisms to stress conditions. Few studies have addressed TA systems in and their role in the adaptation to food environments and processes. In this work, for six strains belonging to group isolated from dairy products, the expression of DinJ-YafQ TA system was investigated after exposure to various food-related stresses (nutrient starvation, low pH, high salt concentration, oxidative stress, and high temperature), as well as to the presence of antibiotics.

Structure-activity relationships of flurbiprofen analogues as stabilizers of the amyloidogenic protein transthyretin.

The inherent amyloidogenic potentialof wild type transthyretin (TTR) is enhanced by a large number of point mutations, which destabilize the TTR tetramer, thereby promoting its disassembly and pathological aggregation responsible for TTR-related amyloidosis. TTR stabilizers are able to interact with the thyroxine-binding sites of TTR, stabilizing its tetrameric native state and inhibiting amyloidogenesis. Herein, we report on in vitro, ex vivo, and X-ray analyses to assess the TTR structural stabilization by analogues of flurbiprofen, a non-steroidal anti-inflammatory drug (NSAID).

Identification and first characterization of DinJ-YafQ toxin-antitoxin systems in Lactobacillus species of biotechnological interest.

DinJ-YafQ is a type II TA system comprising the ribosome-dependent RNase YafQ toxin and the DinJ antitoxin protein. Although the module has been extensively characterized in Escherichia coli, little information is available for homologous systems in lactic acid bacteria. In this study, we employed bioinformatics tools to identify DinJ-YafQ systems in Lactobacillus casei, Lactobacillus paracasei and Lactobacillus rhamnosus species, commonly used in biotechnological processes.

Diatom Allantoin Synthase Provides Structural Insights into Natural Fusion Protein Therapeutics.

Humans have lost the ability to convert urate into the more soluble allantoin with the evolutionary inactivation of three enzymes of the uricolytic pathway. Restoration of this function through enzyme replacement therapy can treat severe hyperuricemia and Lesch-Nyhan disease. Through a genomic exploration of natural gene fusions, we found that plants and diatoms independently evolved a fusion protein (allantoin synthase) complementing two human pseudogenes.

Toward the identification of a type I toxin-antitoxin system in the plasmid DNA of dairy Lactobacillus rhamnosus.

Plasmids carry genes that give bacteria beneficial traits and allow them to survive in competitive environments. In many cases, they also harbor toxin-antitoxin (TA) systems necessary for plasmid maintenance. TA systems are generally characterized by a stable "toxin", a protein or peptide capable of killing the cell upon plasmid loss and by an unstable "antitoxin", a protein or a non-coding RNA that inhibits toxin activity.

Catalysis and Structure of Zebrafish Urate Oxidase Provide Insights into the Origin of Hyperuricemia in Hominoids.

Urate oxidase (Uox) catalyses the first reaction of oxidative uricolysis, a three-step enzymatic pathway that allows some animals to eliminate purine nitrogen through a water-soluble compound. Inactivation of the pathway in hominoids leads to elevated levels of sparingly soluble urate and puts humans at risk of hyperuricemia and gout. The uricolytic activities lost during evolution can be replaced by enzyme therapy.