Evaluation of bronchial hyperresponsiveness in asthmatic paediatric patients using mannitol challenge test - Impacts of body mass index.

Background: Increasing epidemiological studies reported that overweight/obese asthma patients had more frequent and severe symptoms and exacerbations, indicating their asthma management may not be sufficient. Airway hyperresponsiveness (AHR), a significant feature of asthma, was found to link with the body mass index (BMI) with mixed findings using the "direct" methacholine challenge test. The objective was to examine the association between BMI and asthma control, as reflected by the "indirect" AHR with the mannitol challenge test in a paediatric asthmatic population.

Robust peptide/RNA complexes prepared with microfluidic mixing for pulmonary delivery by nebulisation.

Small interfering RNA (siRNA) and messenger RNA (mRNA) have drawn considerable attention in recent years due to their ability to modulate the expression of specific disease-related proteins. However, it is difficult to find safe, robust, and effective RNA delivery systems suitable for pulmonary delivery to treat lung diseases. In this study, two cationic peptides, namely LAH4-L1 and PEGKL4, were employed as non-viral vectors for siRNA and mRNA delivery.

Comparing home polysomnography with transcutaneous CO monitoring to laboratory polysomnography in children with neuromuscular disorders.

Study Objectives: Clinical utility of home polysomnography in children with neuromuscular disorders is limited by lack of evidence that sleep-disordered breathing can be reliably identified and inability to diagnose hypoventilation as carbon dioxide is not measured.

Methods: This study aimed to determine feasibility, accuracy and parent satisfaction for home polysomnography performed with a Type 2 portable monitoring device and a transcutaneous CO monitor. Results of laboratory and home polysomnography were compared with Mann-Whitney U tests and random intercept regression models.

Phage-derived polysaccharide depolymerase potentiates ceftazidime efficacy against Acinetobacter baumannii pneumonia via low-serum-dependent mechanisms.

The emergence of multidrug-resistant Acinetobacter baumannii (MDR-AB), which most commonly manifests as pneumonia, has posed significant clinical challenges and called for novel treatment strategies. Phage depolymerases, which degrade bacterial surface carbohydrates, have emerged as potential antimicrobial agents. However, their preclinical application is limited to systemic infections due to their dependency on serum-mediated bacterial killing.

The Psychometric Performance of the Kansas City Cardiomyopathy Questionnaire-12 in Symptomatic Obstructive Hypertrophic Cardiomyopathy.

Background: A primary goal of treating patients with obstructive hypertrophic cardiomyopathy (oHCM) is to improve their symptoms, function and quality of life. Although the psychometric properties of the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ-23) have been described in oHCM, they have not been assessed for the shorter 12-item version (KCCQ-12), which is used increasingly in clinical practice.

Methods And Results: Using data from the EXPLORER-HCM trial, the psychometric properties of the KCCQ-12 were evaluated.

The Kansas City Cardiomyopathy Questionnaire in Relation to New York Heart Association Class.

Background: In order to identify candidacy and treatment response for patients with obstructive hypertrophic cardiomyopathy (oHCM), clinicians need an accurate means of assessing symptoms, function, and quality of life. While the New York Heart Association (NYHA) Classification is most often used for this purpose, the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) is more accurate and sensitive to change, although less familiar to practicing clinicians. To support interpreting the KCCQ-23, we describe cross-sectional and longitudinal changes in KCCQ scores in the context of the NYHA.

Childhood trauma, resilience, psychopathology and social functioning in schizophrenia: A network analysis.

The affective pathway to psychosis implicates affective symptoms and neuroticism as mediating steps between childhood trauma and symptoms of schizophrenia. Prior research seldom examined the interplay between childhood trauma, resilience, personality, social functioning and symptoms in schizophrenia patients. This study recruited 290 schizophrenia patients, and constructed a regularized partial correlation network of childhood trauma, resilience, big-five personality traits, symptoms and social functioning.

Objective monitoring tools for improved management of childhood asthma.

Asthma is a common chronic disease amongst children. Epidemiological studies showed that the mortality rate of asthma in children is still high worldwide. Asthma control is therefore essential to minimize asthma exacerbations, which can be fatal if the condition is poorly controlled.

Oral Delivery of Photopolymerizable Nanogels Loaded with Gemcitabine for Pancreatic Cancer Therapy: Formulation Design, and in vitro and in vivo Evaluations.

Background: Gemcitabine (GEM) faces challenges of poor oral bioavailability and extensive first-pass metabolism. Currently, only injectable formulations are available for clinical use. Hence, there is an urgent demand for the development of advanced, efficacious, and user-friendly dosage forms to maintain its status as the primary treatment for pancreatic ductal adenocarcinoma (PDAC).

Synergistic combination of antimicrobial peptide and isoniazid as inhalable dry powder formulation against multi-drug resistant tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB) has posed a serious threat to global public health, and antimicrobial peptides (AMPs) have emerged to be promising candidates to tackle this deadly infectious disease. Previous study has suggested that two AMPs, namely D-LAK120-A and D-LAK120-HP13, can potentiate the effect of isoniazid (INH) against mycobacteria. In this study, the strategy of combining INH and D-LAK peptide as a dry powder formulation for inhalation was explored.

Storage stability of lysostaphin solution and its pulmonary delivery.

Methicillin-resistant Staphylococcus aureus (MRSA) has become a leading causative pathogen of nosocomial pneumonia with an alarming in-hospital mortality rate of 30%. Last resort antibiotic, vancomycin, has been increasingly used to treat MRSA infections, but the rapid emergence of vancomycin-resistant strains urges the development of alternative treatment strategies against MRSA-associated pneumonia. The bacteriolytic enzyme, lysostaphin, targeting the cell wall peptidoglycan of S.

Co-delivery of PD-L1- and EGFR-targeting siRNAs by synthetic PEG-KL4 peptide to the lungs as potential strategy against non-small cell lung cancer.

Background: Small interfering RNA (siRNA) holds great promise for treating various lung diseases, but the lack of safe and efficient pulmonary siRNA delivery systems has hindered its advance into the clinics. The epidermal growth factor receptor (EGFR) which promotes cell proliferation, and the programmed cell death ligand 1 (PD-L1) which plays a crucial role in suppressing cytotoxic T cells activity, are two important targets for treating non-small cell lung cancer (NSCLC). Here, we explored the potential of PEG-KL4, a synthetic peptide, to deliver siRNA to various NSCLC cells and to lung tissues in mice.

Modifications to 1-(4-(2-Bis(4-fluorophenyl)methyl)sulfinyl)alkyl Alicyclic Amines That Improve Metabolic Stability and Retain an Atypical DAT Inhibitor Profile.

Atypical dopamine transporter (DAT) inhibitors have shown therapeutic potential in the preclinical models of psychostimulant use disorders (PSUD). In rats, 1-(4-(2-((bis(4-fluorophenyl)methyl)sulfinyl)ethyl)-piperazin-1-yl)-propan-2-ol () was effective in reducing the reinforcing effects of both cocaine and methamphetamine but did not exhibit psychostimulant behaviors itself. Improvements in DAT affinity and metabolic stability were desirable for discovering pipeline drug candidates.

Discovery of -Butyl Ester Based 6-Diazo-5-oxo-l-norleucine Prodrugs for Enhanced Metabolic Stability and Tumor Delivery.

The glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) exhibits remarkable anticancer efficacy; however, its therapeutic potential is hindered by its toxicity to gastrointestinal (GI) tissues. We recently reported the discovery of DRP-104, a tumor-targeted DON prodrug with excellent efficacy and tolerability, which is currently in clinical trials. However, DRP-104 exhibits limited aqueous solubility, and the instability of its isopropyl ester promoiety leads to the formation of an inactive M1-metabolite, reducing overall systemic prodrug exposure.

Obesity management for the hepatologist-What to do, how to do it and why?

Obesity is highly prevalent in hepatology clinics and has a significant impact on chronic liver disease and patient management. Hepatologists and gastroenterologists need to be actively engaged in the management of obesity. This review provides a detailed approach to this challenging comorbidity.

Turner syndrome: skin, liver, eyes, dental and ENT evaluation should be improved.

Introduction: Turner syndrome association with multi-organ system comorbidities highlights the need for effective implementation of follow-up guidelines. We aimed to assess the adequacy of care with international guidelines published in 2007 and 2017 and to describe the phenotype of patients.

Methods: In this multicenter retrospective descriptive cohort study, we collected growth and pubertal parameters, associated comorbidities, treatment, and karyotype in patients diagnosed at age <18 years between 1993 and 2022.

Delivery technology of inhaled therapy for asthma and COPD.

Inhaled therapy is the cornerstone of the management of asthma and chronic obstructive pulmonary disease (COPD). Drugs such as bronchodilators and corticosteroids are administered directly to the airways for local effect and rapid onset of action while systemic exposure and side effects are minimized. There are four major types of inhaler devices used clinically to generate aerosols for inhalation, namely, pressurized metered-dose inhalers (pMDIs), nebulizers, Soft Mist™ inhalers (SMIs) and dry powder inhalers (DPIs).

Enhanced powder dispersion of dual-excipient spray-dried powder formulations of a monoclonal antibody and its fragment for local treatment of severe asthma.

The advent of biologics has brought renewed hope for patients with severe asthma, a condition notorious for being hampered by poor response to conventional therapies and adverse drug reactions owing to corticosteroid dependence. However, biologics are administered as injections, thereby precluding the benefits inhalation therapy could offer such as increased bioavailability at the site of action, minimal systemic side effects, non-invasiveness, and self-administration. Here, 2-hydroxypropyl-beta-cyclodextrin and ʟ-leucine were co-spray-dried, as protein stabiliser and dispersion enhancer, respectively, at various weight ratios to produce a series of formulation platforms.

Synthesis and Properties of Sucrose- and Lactose-Based Aromatic Ester Surfactants as Potential Drugs Permeability Enhancers.

The delivery of therapeutics across biological membranes (e.g., mucosal barriers) by avoiding invasive routes (e.

Factors Associated With the Quality of Life of Nursing Home Residents During the COVID-19 Pandemic: A Cross-Sectional Study.

Objectives: Quality of life (QoL) of nursing home (NH) residents is critical, yet understudied, particularly during the COVID-19 pandemic. Our objective was to examine whether COVID-19 outbreaks, lack of access to geriatric professionals, and care aide burnout were associated with NH residents' QoL.

Design: Cross-sectional study (July to December 2021).

Neutralisation of SARS-CoV-2 by monoclonal antibody through dual targeting powder formulation.

Neutralising monoclonal antibody (mAb) is an important weapon in our arsenal for combating respiratory viral infections. However, the effectiveness of neutralising mAb has been impeded by the rapid emergence of mutant variants. Early administration of broad-spectrum mAb with improved delivery efficiency can potentially enhance efficacy and patient outcomes.

Co-Delivery of D-LAK Antimicrobial Peptide and Capreomycin as Inhaled Powder Formulation to Combat Drug-Resistant Tuberculosis.

Introduction: The emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) posed a severe challenge to tuberculosis (TB) management. The treatment of MDR-TB involves second-line anti-TB agents, most of which are injectable and highly toxic. Previous metabolomics study of the Mtb membrane revealed that two antimicrobial peptides, D-LAK120-A and D-LAK120-HP13, can potentiate the efficacy of capreomycin against mycobacteria.

Inhalable neutralizing antibodies - promising approach to combating respiratory viral infections.

Monoclonal antibodies represent an exciting class of therapeutics against respiratory viral infections. Notwithstanding their specificity and affinity, the conventional parenteral administration is suboptimal in delivering antibodies for neutralizing activity in the airways due to the poor distribution of macromolecules to the respiratory tract. Inhaled therapy is a promising approach to overcome this hurdle in a noninvasive manner, while advances in antibody engineering have led to the development of unique antibody formats which exhibit properties desirable for inhalation.