Search Results (136)

Background: Treatment compliant with the Global Initiative for Asthma (GINA) can promote more effective disease control. Single-inhaler triple therapy (SITT) is one method that is used to optimize therapy in this context, but TRIPLE therapy is still employed by physicians to a limited extent. Objective: This study aimed to describe the factors influencing challenges in optimizing asthma therapy. Methods: A 19-question survey, created via the CATI system, was distributed among pulmonologists, allergologists, general practitioners, and internal medicine specialists in Poland, Greece, Sweden, Slovenia, and Austria. Results: Statistically significant percentage differences in the use of TRIPLE therapy in the context of asthma management were observed among countries as well as between pulmonologists, allergists, and other specialists. Overuse of oral corticosteroids (OCSs) to treat nonsevere and severe asthma in the absence of an approach that focuses on optimizing inhalation therapy among asthma patients receiving TRIPLE therapy was observed in different countries as well as among physicians with different specialties. Twenty elements associated with the challenges involved in diagnosing and managing difficult-to-treat and severe asthma were identified. Six clinical categories for the optimization of asthma therapy via SITT were highlighted. The degree of therapeutic underestimation observed among severe asthma patients was assessed by comparing actual treatment with the recommendations of the GINA 2023 guidelines. Conclusions: Physicians of various specialties in Europe are subject to therapeutic inertia in terms of their compliance with the GINA 2023 guidelines. Full article

Background: Allergic rhinitis (AR) is a prevalent allergic disorder characterized by a complex pathogenesis. Drawing on traditional Chinese medicine theory and contemporary pharmacological principles, this study developed an inhalation-based herbal formulation, ZHW, to explore a novel non-invasive therapeutic approach. Objective: To investigate the therapeutic effects of ZHW on AR and elucidate its underlying mechanisms and potential targets through an integrated analysis of network pharmacology and proteomics. Materials and Methods: The volatile components of ZHW were analyzed by gas chromatography–mass spectrometry (GC-MS). The mouse model of AR was induced by OVA sensitization. The therapeutic efficacy of ZHW was assessed based on nasal symptom scores, histopathological examination, and inflammatory cytokine levels. Furthermore, the underlying mechanisms and potential targets of ZHW were investigated through integrated network pharmacology and proteomics analyses. Results: GC-MS analysis identified 39 bioactive compounds in ZHW. Inhalation treatment with ZHW demonstrated significant anti-allergic effects in OVA-sensitized mice, as evidenced by (1) reduced sneezing frequency and nasal rubbing behaviors; (2) decreased serum levels of IL-4, histamine, and OVA-specific IgE; (3) attenuated IL-4 concentrations in both nasal lavage fluid and lung tissue; (4) diminished nasal mucosal thickening; and (5) suppression of inflammatory cell infiltration. Integrated network pharmacology and proteomics analyses indicated that ZHW’s therapeutic effects were mediated through the modulation of multiple pathways, including the PI3K-Akt signaling pathway, the B cell receptor signaling pathway, oxidative phosphorylation, and the FcεRI signaling pathway. Key molecular targets involved Rac1, MAPK1, and SYK. Molecular docking simulations revealed strong binding affinities between ZHW’s primary bioactive constituents (linalool, levomenthol, linoleic acid, Linoelaidic acid, and n-Valeric acid cis-3-hexenyl ester) and these target proteins. Conclusions: The herbal formulation ZHW demonstrates significant efficacy in alleviating allergic rhinitis symptoms through multi-target modulation of key signaling pathways, including PI3K-Akt- and FcεRI-mediated inflammatory responses. These findings substantiate ZHW’s therapeutic potential as a novel, non-invasive treatment for AR and provide a strong basis for the development of new AR therapies. Future clinical development will require systematic safety evaluation to ensure optimal therapeutic outcomes. Full article

Asthma is a highly heterogeneous respiratory disease that, in its severe forms, is characterized by persistent symptoms, frequent exacerbations, and a significant impact on patients’ quality of life. Despite high-dose inhaled corticosteroids and long-acting bronchodilators, a subset of patients remains uncontrolled, necessitating advanced therapeutic strategies. The advent of biologic therapies has revolutionized the management of severe asthma, offering targeted interventions based on the underlying inflammatory endotypes, primarily T2-high and T2-low. However, selecting the most appropriate biologic remains challenging due to overlapping phenotypic features and the limited availability of validated biomarkers. This narrative review explores the clinical utility of key biomarkers, including blood eosinophils, fractional exhaled nitric oxide (FeNO), periostin, and total and specific IgE, in guiding biologic therapy. All the information provided is based on an extensive literature search conducted on PubMed. We also examine the clinical characteristics and comorbidities that influence therapeutic choices. Furthermore, we present a practical decision-making platform, including a clinical table matching phenotypes with biologic agents, such as omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab. By integrating biomarker analysis with clinical assessment, based on current guidelines and our extensive real-life experience, we aim to offer a logical framework to help clinicians select the most suitable biologic treatment for patients with uncontrolled severe asthma. Future research should focus on identifying novel biomarkers, refining patient stratification, and evaluating long-term outcomes to further advance precision medicine in the management of severe asthma. Full article

Purpose: Suicide is a leading cause of death among children and adolescents worldwide. This study examined the prevalence and characteristics of suicides among children and adolescents (aged ≤ 19 years) over a 13-year period in the broader area of Athens, Greece. Key aspects analyzed included victim demographics, circumstances surrounding the incidents, and methods employed. Methods: A retrospective analysis was conducted on autopsy cases performed at the Department of Forensic Medicine and Toxicology, National and Kapodistrian University of Athens, from 1 January 2011, to 31 December 2023. Results: Out of 5819 autopsies conducted between 2011 and 2023, 371 were classified as suicides. Among these, 12 cases (representing 3.2% of suicides) involved children and adolescents aged ≤ 19 years and met the study’s inclusion criteria for detailed forensic analysis. The average age of the victims was 17.7 ± 2.1 years (range: 14–19), with males representing 58.3% of cases. Hanging was the most common method of suicide (9 cases, 75.0%), followed by firearm use, falls from height, and hydrogen sulfide inhalation (one case each). Death occurred in the home in 10 cases (83.3%), with 6 specifically taking place in the bedroom. Scars indicative of prior self-harming behavior were present in two cases (16.7%), while suicide notes were found in three cases (25.0%). Toxicological analysis revealed alcohol and cannabis use in one case, cannabis alone in one case, and alcohol alone in two cases. Four victims (33.3%) had a documented psychiatric diagnosis, with two of them under antidepressant treatment at the time of death. Conclusions: This study highlights the forensic value of autopsy-based investigations in unveiling hidden patterns of adolescent suicidality and informs targeted prevention strategies. Integrating medico-legal findings into public health responses may enhance early identification and intervention in vulnerable youth populations. Full article

Anxiety disorders, as common neurological diseases in clinical practice, often coexist with depression. Epidemiological surveys indicate that approximately 85% of patients with depression exhibit significant anxiety symptoms. This comorbid state not only exacerbates clinical symptoms but also leads to treatment resistance and prolonged disease duration. This study innovatively developed a compound aromatic plant essential oil (EO) formulation with remarkable anxiolytic and antidepressant effects and systematically elucidated its mechanism of action. The study found that the essential oil formulation, administered via inhalation, could significantly improve behavioral abnormalities in animals subjected to the chronic unpredictable mild stress (CUMS) model, specifically manifesting as (1) the reversal of stress-induced weight gain retardation; (2) a significant increase in sucrose preference; (3) an increase in the total distance of spontaneous activity; and (4) the prolongation of exploration time in the open arms of the elevated plus maze. Neuropathological examinations confirmed that the formulation could effectively protect the structural integrity of hippocampal neurons and alleviate CUMS-induced neural damage. In terms of mechanism of action, the study revealed that the formulation regulates the neurotransmitter system through multiple targets: (1) the upregulation of serotonin (5-HT) and γ-aminobutyric acid (GABA) levels; (2) the downregulation of glutamate (GLU) concentration; and (3) key targets identified via network pharmacological analysis, such as ESR1, STAT3, and PPARG. These findings provide molecular-level evidence for understanding the neuromodulatory effects of aromatic essential oils. Pharmaceutical formulation studies showed that the oil-in-water (O/W) type compound essential oil microemulsion, prepared using microemulsification technology, has a uniform particle size and excellent stability, maintaining stable physicochemical properties at room temperature for an extended period, thus laying a foundation for its clinical application. This study not only validates the practical value of traditional medicine but also provides new ideas for the development of novel anxiolytic and antidepressant drugs, achieving an organic integration of traditional experience and modern technology. Full article

Nitrous oxide (N₂O) was originally used for medical and industrial purposes, but its recreational use has dramatically increased, raising a major global public health concern. Chronic inhalation is associated with neurological, metabolic, and psychiatric complications, as well as addiction. To address these challenges, the PROTOSIDE network was developed to provide a multidisciplinary approach to management and prevention. This initiative relies on competence centers integrating specialists in emergency medicine, neurology, clinical biochemistry, and addiction medicine. PROTOSIDE aims to standardize diagnostic protocols, optimize patient care pathways, and strengthen addictovigilance. A strong emphasis is placed on prevention, including awareness campaigns and collaboration with healthcare professionals and educators. By facilitating access to advanced biochemical analyses (homocysteine, methylmalonic acid) and promoting international guidelines, PROTOSIDE represents an innovative model for a global response to N₂O misuse. This integrated approach enhances clinical management, reduces complications, and harmonizes public health strategies. Full article

The replication machinery of SARS-CoV-2 is a primary target for therapeutic intervention, and has led to significant progress in antiviral medication discovery. This review consolidates contemporary molecular insights into viral replication and rigorously assesses treatment methods at different phases of viruses’ clinical development. Direct-acting antivirals, such as nucleoside analogs (e.g., remdesivir, molnupiravir) and protease inhibitors (e.g., nirmatrelvir), have shown clinical effectiveness in diminishing morbidity and hospitalization rates. Simultaneously, host-targeted medicines like baricitinib, camostat, and brequinar leverage critical host–virus interactions, providing additional pathways to reduce viral replication while possibly minimizing the development of resistance. Notwithstanding these advancements, constraints in distribution methods, antiviral longevity, and the risk of mutational evasion demand novel strategies. Promising investigational approaches encompass CRISPR-mediated RNA degradation systems, inhalable siRNA-nanoparticle conjugates, and molecular glue degraders that target host and viral proteins. Furthermore, next-generation treatments aimed at underutilized enzyme domains (e.g., NiRAN, ExoN) and host chaperone systems (e.g., TRiC complex) signify a transformative approach in antiviral targeting. The integration of high-throughput phenotypic screening, AI-driven medication repurposing, and systems virology is transforming the antiviral discovery field. An ongoing interdisciplinary endeavor is necessary to convert these findings into versatile, resistance-resistant antiviral strategies that are applicable beyond the present pandemic and in future coronavirus epidemics. Full article

Antimicrobial resistance (AMR) is a major global concern in both human and veterinary medicine. Among antimicrobial resistance (AMR) bacteria, Extended-Spectrum Beta-Lactamases (ESBLs) pose a serious health risk because infections can be difficult to treat. These Gram-negative bacteria can be frequently found in poultry and in Italy, where such protein production is established. ESBL-producing Escherichia coli, Salmonella and Klebsiella in chicken and turkey may pose a significant public health risk due to potential transmission between poultry and humans. This review aims to assess the prevalence of ESBL-producing E. coli, Salmonella and Klebsiella phenotypically and genotypically in Italian poultry, identifying the most common genes, detection methods and potential information gaps. An initial pool of 1462 studies found in scientific databases (Web of Sciences, PubMed, etc.) was screened and 29 were identified as eligible for our review. Of these studies, 79.3% investigated both phenotypic and genotypic ESBL expression while ${bla}_{CTX-M}$, ${bla}_{TEM}$ and ${bla}_{SHV}$ were considered as targeted gene families. Large differences in prevalence were reported (0–100%). The ${bla}_{CTX-M-1}$ and ${bla}_{TEM-1}$ genes were the most prevalent in Italian territory. ESBL-producing E. coli, Salmonella and Klebsiella were frequently detected in farms and slaughterhouses, posing a potential threat to humans through contact (direct and indirect) with birds through handling, inhalation of infected dust, drinking contaminated water, ingestion of meat and meat products and the environment. Considering the frequent occurrence of ESBL-producing bacteria in Italian poultry, it is advisable to further improve biosecurity and to introduce more systematic surveillance. Additionally, the focus should be on the wild birds as they are ESBL carriers. Full article

Multidrug-resistant tuberculosis (MDR-TB) is a significant public health challenge globally, exacerbated by the limited efficacy of existing therapeutic approaches, prolonged treatment duration, and severe side effects. As drug resistance continues to emerge, innovative drug delivery systems and treatment strategies are critical to combating this crisis. This review highlights the molecular mechanisms underlying resistance to drugs in Mycobacterium tuberculosis, such as genetic mutation, efflux pump activity, and biofilm formation, contributing to the persistence and difficulty in eradicating MDR-TB. Current treatment options, including second-line drugs, offer limited effectiveness, prompting the need for innovation of advanced therapies and drug delivery systems. The progression in drug discovery has resulted in the approval of innovative therapeutics, including bedaquiline and delamanid, amongst other promising candidates under investigation. However, overcoming the limitations of traditional drug delivery remains a significant challenge. Nanotechnology has emerged as a promising solution, with nanoparticle-based drug delivery systems offering improved bioavailability and targeted and controlled release delivery, particularly for pulmonary targeting and intracellular delivery to macrophages. Furthermore, the development of inhalable formulations and the potential of nanomedicines to bypass drug resistance mechanisms presents a novel approach to enhancing drug efficacy. Moreover, adjunctive therapies, including immune modulation and host-directed therapies, are being explored to improve treatment outcomes. Immunotherapies, such as cytokine modulation and novel TB vaccines, offer complementary strategies to the use of antibiotics in combating MDR-TB. Personalized medicine approaches, leveraging genomic profiling of both the pathogen and the host, offer promise in optimizing treatment regimens and minimizing drug resistance. This review underscores the importance of multidisciplinary approaches, combining drug discovery, advanced delivery system development, and immune modulation to address the complexities of treating MDR-TB. Continued innovation, global collaboration, and improved diagnostics are essential to developing practical, accessible, and affordable treatments for MDR-TB. Full article

Chronic Obstructive Pulmonary Disease (COPD) manifests as a genetically diverse and intricate lung condition with various subtypes. The development of the disease and response to treatment are influenced by the interplay between genetic and environmental factors. The predominant therapeutic approaches include bronchodilator therapy and corticosteroid treatment. Studies in COPD pharmacogenetics involve genome-wide association (GWA) studies, gene profiling, whole-genome sequencing, and other omics-based investigations. Many of these investigations have focused on the association between genetic variations and the response to β2 agonist treatment. Additionally, several studies have explored the impact of gene variations on the response to inhaled corticosteroid (ICS) treatment, with a specific focus on polymorphisms in the glucocorticoid receptor (GR) signaling pathway. However, a significant challenge lies in the inconclusive or inconsistent results of these pharmacogenetic studies, underscoring the research community’s struggle to provide sufficient evidence for the clinical implementation of COPD pharmacogenetics. To address these challenges, further research and larger genome-wide studies are essential. These efforts aim to uncover additional COPD subtypes, identify predictors of treatment response, and discover novel genetic markers for COPD. The integration of genomics, detailed evaluations such as chest CT scans, spirometry tests, and blood analyses, along with DNA collection in clinical research, is critical for translating COPD pharmacogenetics into clinical practice. Furthermore, advancing our understanding of the complex interactions between genetics, phenotypes, and environmental factors will be pivotal for improving individualized prognostic assessments and enhancing treatment outcomes in COPD. Full article

Background: In the cardio-respiratory rehabilitation field, thermal medicine represents an interesting complementary therapy approach. It can aid in complex medical contexts characterized by cardio-respiratory deficiency, functional limitation, and pain determined by the invasiveness of pharmacological and surgical treatments in combination with limited post-surgical physical activity. Methods: We investigated the evolution of cardio-respiratory and functional performances following the application of the Integrated Thermal Care (ITC) protocol in 11 mastectomized/quadrantectomized women (mean age of 54 years). The ITC protocol consisted of hydroponic treatments, steam inhalations treatment, hydrokinesitherapy, and manual treatments. Patients were assessed before and after a cycle of 1 h long treatment sessions, which were performed 5 days a week for 4 weeks. The outcomes were measured through the following scales and tests: Piper Fatigue Scale (PIPER), 6-Minute Walking Test (6MWT), Five Times Sit-to-Stand (5STS), Range of Arm Motion (ROM), Disability of the Arm–Shoulder–Hand Scale (DASH), and Numeric Pain Rating Scale (NPRS). Results: We found appreciable improvements in cardio-respiratory efficiency and in pain perception exemplified by a reduction of PIPER, 5STS, DASH, and NPRS values together with an increase in 6MWT and ROM values. Conclusions: We conclude that ITC is a promising rehabilitative tool to enhance cardio-respiratory and functional performance and reduce pain after mastectomy/quadrantectomy. Full article

Background: Depression ranks among the most severe mental health conditions, and poses a burden on global health. Agarwood, an aromatic medicinal plant, has shown potential for improving mental symptoms. As a common folk medicine, agarwood has been applied as an alternative method for mental disorders such as depression through aromatherapy. Previous studies have found that the therapeutic effects of agarwood aromatherapy are primarily related to its volatile components. This study aimed to examine the antidepressant properties and underlying mechanisms of agarwood essential oil (AEO), a collection of the volatile components of agarwood utilized through aromatherapy inhalation and injection administration in mice. Methods: A lipopolysaccharide (LPS)-induced inflammatory depression model was used to evaluate the effects of AEO inhalation and injection on depression-like symptoms. Behavioral assessments included the open-field, tail suspension, and forced swimming tests. Western blot (WB) and ELISA techniques were used to further verify the mechanistic insights. Results: In the LPS-induced depression-like model, AEO inhalation and injection significantly improved depression-like symptoms, decreased immobility duration in both the tail suspension and forced swimming tests in model mice, and reduced the levels of inflammatory cytokines IL-1β, IL-6, and TNF-α. WB experiments demonstrated that AEO inhibited the NF-κB/IκB-α inflammatory pathway and activated the BDNF/TrkB/CREB pathway in the hippocampus of the LPS-depression model mice. Notably, AEO extracted by hydrodistillation was more effective in alleviating LPS-induced depressive-like behaviors than using supercritical CO₂ fluid extraction. Conclusions: Both the inhalation and the injection administration of AEO exerted notable antidepressant effects, potentially associated with reducing inflammation levels in the brain, downregulating inflammatory NF-κB/IκB-α, and upregulating the neuroprotective BDNF/TrkB/CREB signaling pathway. In the future, it is necessary to further determine the pharmacodynamic components, key targets and specific molecular mechanisms of AEO’s antidepressant effects so as to provide more support for the neuroprotective research of medicinal plants. Full article

Pulmonary arterial hypertension (PAH) is a chronic and progressive disease marked by vascular remodeling, inflammation, and smooth muscle cell proliferation, with limited treatment options focused primarily on symptom management. The multifactorial nature of PAH, encompassing genetic, autoimmune, and connective tissue contributions, complicates its treatment, while irreversible vascular changes, such as fibrosis, remain unaddressed by current therapies. Fundamental research on molecular pathways and targeted delivery systems has paved the way for advanced therapeutic strategies that aim to modify disease progression rather than merely manage symptoms. Nanoparticle-based drug delivery systems, leveraging controlled release and pulmonary targeting, offer a promising avenue to overcome these challenges. Such systems enable precise localization to pulmonary vasculature, minimize systemic side effects, and support emerging approaches like gene therapy and combination treatments. Future research should focus on refining nanoparticle formulations for personalized medicine, optimizing inhalation delivery systems, and integrating multi-target approaches to achieve curative outcomes in PAH. This review explores pathophysiology of PAH, current pharmacological strategies, and innovative nanoparticle-based therapies, emphasizing their potential to transform PAH treatment and address its underlying mechanisms. Full article

Background: Angiotensin-converting enzyme inhibitors, such as enalapril, are foundational in treating pediatric heart failure. However, they are often administered off-label to young children using extemporaneous formulations. This study, conducted as part of the EU-funded Labeling of Enalapril from Neonates up to Adolescents (LENA) project, aimed to evaluate the acceptability and palatability of an age-appropriate enalapril orodispersible minitablet (ODMT). These factors are critical for ensuring adherence, efficacy, and safety in pediatric patients. Methods: An 8-week trial was conducted in children with heart failure caused by dilated cardiomyopathy or congenital heart disease. Enalapril ODMTs (0.25 mg or 1.0 mg) were dose-titrated and administered to 38 children aged 0–6 months and 22 children aged 6 months to 6 years. This study aimed to assess its acceptability and palatability, key factors contributing to adherence, and therefore, efficacy and safety. Results: Across all 169 assessments in 38 children aged 0–6 months and 22 aged 6 months to 6 years, complete or partial swallowability was observed, and the acceptability rate was 100%. There were no cases of choking, inhalation/coughing, or spitting out. A favorable or neutral rating was observed in 96% of palatability assessments based on observations of facial expressions. Acceptability and palatability were higher in subjects aged 6 months–6 years than 0–6 months, with no significant influence from repeated administration. Conclusions: Enalapril ODMTs are widely accepted and well-tolerated among young children, including neonates, with heart failure. These findings suggest that ODMTs are a suitable and effective method for administering pediatric medicinal products. Full article

Complementary and alternative medicine (CAM) encompasses a variety of ancient therapies with origins in cultures such as those of China, Egypt, Greece, Iran, India, and Rome. The National Institutes of Health (NIH) classifies these integrative therapies into five categories: (1) mind–body therapies, (2) biological practices, (3) manipulative and body practices, (4) energy medicine, and (5) whole medical systems, including traditional Chinese medicine and Ayurvedic medicine. This review explores the role of biological practices utilizing aromatic plants, particularly through inhalation aromatherapy and massage with essential oils, as effective complementary strategies within health systems. The review compiles information on the most commonly used plants and essential oils for holistic health maintenance from a complementary and alternative perspective. Given their accessibility and relative safety compared to conventional treatments, these therapies have gained popularity worldwide. Furthermore, the integration of essential oils has been shown to alleviate various psychological and physiological symptoms, including anxiety, depression, fatigue, sleep disorders, neuropathic pain, nausea, and menopausal symptoms. Among the studied plants, lavender has emerged as being particularly notable due to its broad spectrum of therapeutic effects and its designation by the US Food and Drug Administration (FDA) as “Generally Recognized as Safe”. Other essential oils under investigation include eucalyptus, damask rose, sandalwood, vetiver, calamus, frankincense, chamomile, lemon, grapefruit, tangerine, orange, sage, rosemary, garlic, and black pepper. This study emphasizes the potential benefits of these aromatic plants in enhancing patient well-being. Additionally, it underscores the importance of conducting further research to ensure the safety and efficacy of these therapies. Full article