Search Results (3,723)

Respiratory infections remain a significant global health concern, especially as multidrug-resistant (MDR) respiratory pathogens reduce the effectiveness of conventional antibiotics. Patients with chronic lung diseases face persistent biofilm-related infections that are difficult to treat, underscoring the urgency for new solutions. This challenge has renewed focus on bacteriophage therapy as a promising alternative in respiratory antimicrobial management. Bacteriophages are viruses that selectively infect and lyse bacteria, showing strong potential as a precise and effective therapy for resistant pulmonary infections. This review focuses on the mechanisms of phage biology and therapy in lung infections, highlighting their unique interactions with mucus, surfactants, and immune defenses—all of which are central to their clinical promise. The review examines advances in phage engineering, delivery strategies, and inhaled formulations aimed at maximizing phage stability and targeting within the airways. It summarizes recent preclinical and clinical progress targeting MDR respiratory pathogens and discusses regulatory, manufacturing, and safety considerations key to integrating phage therapy into mainstream respiratory care. Full article

Background: Chronic Obstructive Pulmonary Disease (COPD) is a common condition that can cause dyspnea, pain, and biomechanical-postural alterations, especially when overlapping with Myofascial Pain Syndrome (MPS). Balneological rehabilitation medicine can help manage COPD and MPS, but it lacks homogeneity and detailed descriptions of effective therapeutic protocols. Therefore, we conducted a case series to preliminarily evaluate the clinical effects of a detailed and codified approach, called Bio-Physico-Metric Integrated Thermal Care (BPM-ITC), for COPD+MPS. Methods: 10 patients were observed while undergoing 20 sessions of BPM-ITC in 4 weeks. Patients were assessed before and after the protocol using the Medical Research Council (MRC) dyspnea scale, Numeric Pain Rating Scale (NPRS), and the Bio-Postural Questionnaire (BPQ) for bio-physical health status. Treatments included manual therapy of key myofascial trigger points combined with crenotherapy, steam inhalations, mud therapy, vascular path, and water-based motor re-education. Results: At the end of the protocol, clinically relevant improvements were observed in almost all parameters considered in single observed cases; overall statistical analysis of the data highlighted significant positive effects in concomitance with the BPM-ITC protocol. Conclusions: The BPM-ITC protocol was followed by significant clinical improvements in the observed cases, suggesting its potential as a complementary approach for COPD+MPS. Further studies on this topic are recommended. Full article

The concentration of heavy metals in the environment has been steadily increasing, raising concerns about their adverse effects on ecosystems and human health. Fine-grained particulate matter is of particular concern due to its enhanced mobility, bioavailability, and potential for inhalation exposure. Facilities involved in the mechanical processing of electronic waste (e-waste) represent a significant potential source of metal-containing fine particles. In this study, crushed e-waste components containing precious metals were separated into particle-size fractions ranging from 3.0 to 0.15 mm using a vibratory sieving system. The elemental composition of the individual fractions was determined by energy-dispersive X-ray fluorescence spectrometry (ED-XRF), while the spatial distribution of selected metals in fine fractions was further investigated using scanning electron microscopy combined with energy-dispersive X-ray spectroscopy (SEM–EDS). The results demonstrate that e-waste contains a wide range of heavy non-ferrous metals whose distribution is strongly dependent on particle size. A pronounced enrichment of metals was observed in the finest fractions, particularly below 0.25 mm. Compared to the coarse fraction (>3 mm), the zinc concentration increased by approximately one order of magnitude, while chromium, nickel, and cadmium exhibited increases of up to approximately 20-fold. Lead showed particularly high enrichment, reaching approximately 2 wt.% in the finest fraction (<0.15 mm), corresponding to nearly fiftyfold enrichment relative to the coarse fraction. Tin concentrations also increased markedly, in some cases by up to two orders of magnitude. Trace amounts of arsenic and selenium were detected in the finest fractions, whereas mercury was not detected. The combined ED-XRF and SEM–EDS results confirm that fine-grained e-waste fractions are the dominant carriers of hazardous metals and respirable particles generated during mechanical processing. These findings highlight the dual character of fine fractions as both a critical environmental and occupational risk and a potentially valuable secondary resource. The study emphasizes the importance of controlled handling, effective dust management, and targeted processing strategies to minimize human exposure while enabling efficient recovery of valuable metals from e-waste. Full article

Hexavalent chromium (Cr(VI)) is a highly toxic and carcinogenic trace element. While carcinogenicity through inhalation is well-established, gastrointestinal (GI) carcinogenicity via oral ingestion remains contentious. This study aimed to measure GI cancer mortality at Oinofyta, Greece, where the toxic waste of industries was discarded in the village’s water source for a long time. An ecological study was carried out at the Oinofyta municipal unit, where the primary water supply had been contaminated with Cr(VI) for approximately three decades. Mortality data of all residents of Oinofyta for the period 2000–2021 were obtained from the Hellenic Statistical Authority, and causes of death were classified according to the ICD-10. Standardized Mortality Ratios (SMRs) were computed, stratified by five-year age groups, biological sex, and calendar year, using the population of the entire Voiotia regional unit as the reference population. A higher all GI cancer SMR was observed during the second decade (SMR = 1.44; 95%CI = 1.03, 1.95), but not the first (SMR = 0.98; 95%CI = 0.64, 1.44). Overall, the SMR was evidently higher for males (SMR = 1.35; 95%CI = 1.0, 1.8), but not for females (SMR = 0.97; 95%CI = 0.6, 1.49). A borderline higher SMR was also observed for colorectal cancer in males (SMR = 1.63; 95%CI = 0.93, 2.65; p = 0.08). Additionally, the SMR for all GI cancers demonstrated a significant increasing trend from 2000–2009 to 2010–2021 (0.98; 95%CI = 0.64, 1.44 to 1.44; 95%CI = 1.03, 1.95). This ecological study presents a population-level association between Cr(VI)-contaminated drinking water with certain GI cancers, suggesting further research for etiological associations. Full article

Tularemia is a plague-like, potentially fatal zoonosis caused by the coccobacillus Francisella tularensis. It was discovered at the beginning of the last century in the United States and was soon recognized in Japan and in the former Soviet Union as the cause of clinical conditions that had been known for one and two centuries, respectively. More than 250 animal species are susceptible to infection, with rodents and lagomorphs serving as key reservoirs, and several vectors may transmit the disease, mainly ticks and mosquitoes. Humans are incidental hosts and are infected primarily by two F. tularensis subspecies, tularensis and holarctica: the former is more severe and is found almost exclusively in North America, whereas the latter is distributed throughout the Northern Hemisphere, mainly in Europe and Asia. Tularemia is highly infectious; therefore, diagnostic cultures should be handled in biosafety level 3 laboratories. Nevertheless, interhuman transmission is exceedingly rare. Although tularemia is relatively uncommon, it shows a re-emerging pattern at the global level, particularly in Europe. As with plague, mitigation may be more effectively achieved through a One Health approach. Neither approved vaccines nor therapeutic antibodies are currently available, whereas aminoglycoside, tetracycline, and quinolone antibiotics are effective. Owing to its high infectivity, its ease of transmission by inhalation, its clinical severity, with a prolonged and debilitating course, and its potential lethality, F. tularensis has long been considered a potential biological weapon, particularly if antibiotic-resistant strains were used. Although natural antibiotic resistance has not been described to date, research programs aimed at obtaining resistant strains have been conducted. It has been suggested that the disease was already present in the Middle East during the second millennium BC; should this hypothesis be confirmed by paleogenomic studies, plague and tularemia would have coexisted for more than three millennia, with plague masking the less severe tularemia. Many challenges related to tularemia are still unresolved. Full article

Coccidioidomycosis (CM) is a fungal infection caused by the inhalation of airborne arthroconidia released by Coccidioides spp. Endemic areas include the southwestern United States, Mexico, and parts of South America. The estimated CM cases exceed 300,000 per year. Current treatment for CM is limited and primarily relies on antifungals such as azoles and Amphotericin B. Moreover, concerns about drug cytotoxicity and rising of azole-resistance underscore the need for alternative or adjunctive immune-based prevention and therapies. This review presents recent advances in immune CM intervention and discusses the potential application of emerging antifungal immunotherapy to treat invasive CM. For preventive vaccination, we reviewed the recent development of subunit protein vaccines and mRNA-based vaccines. Prospects for formulating vaccines with potent adjuvants and delivery systems to enhance protective immunity against CM are also provided. For immunotherapy, we reviewed recent reports of antifungal treatment with immunomodulators, CAR-cells and checkpoint inhibitors. Finally, we discuss the application of experimental animal and in vitro models for advancing vaccine and immunotherapeutic development for CM. Full article

Inorganic lead (Pb) poses a significant public health concern due to its toxicity and widespread industrial use. Dermal contact, an under-researched pathway of Pb exposure relative to inhalation and ingestion, is typically not factored into regulatory exposure limits because of the paucity of validated studies. This study investigated the influence of sweat on the bioaccessibility of inorganic lead for dermal absorption. Dissolution testing was conducted to determine the dissolution kinetics of inorganic Pb (lead nitrate) in synthetic sweat relative to deionized water (DIW). Particle sizes of samples ranged from 0.70 µm to 118 µm. Non-linear dissolution kinetics were observed in both DIW (control) and sweat. The iPb ion concentration in DIW after 3 h (test period) accounted for 100% of the initial mass of iPb, compared to 67% of the initial mass of iPb in sweat. Higher variability was observed in sweat (SD: 1.47 to 8.2) compared to DIW (SD: 0.80 to 3.88). Precipitation was observed in sweat but not in DIW. Wilcoxon rank-sum test indicated a statistically significant difference in dissolution between sweat and deionized water (Z = −4.50, p < 0.0001). Findings suggest that sweat composition limits the extent of dissolution of soluble inorganic Pb, thereby influencing its dermal bioaccessibility. Full article

Background/Objectives: Behavior management is a major challenge in pediatric dentistry, particularly during the first dental visit, when anxiety, fear, and negative expectations can compromise cooperation and clinical outcomes. While evidence-based behavior guidance techniques are well established, their effectiveness depends on early identification of behavioral risk and individualized planning. This study aimed to develop and clinically evaluate a parent-completed digital pre-visit tool to support individualized behavior management and targeted use of digital distraction in pediatric dentistry. Methods: A web-based application was developed using HTML, CSS, and JavaScript. It was applied to a prospective observational cohort of 90 pediatric patients aged 4–8 years (mean 6.1 ± 1.2), including 48 girls and 42 boys. Parents completed a pre-visit questionnaire covering four domains: child’s age, previous dental experiences, reactions to unfamiliar situations, and individual interests, including stimuli to avoid. Based on predefined decision rules, the tool generated recommended clinical approaches, including behavior guidance techniques, digital distraction, and inhalation sedation. Results: Over 90% of children were successfully managed during their first visit. Children in low- and moderate-risk groups had significantly higher odds of treatment success compared to high-risk children. Low-risk children almost universally completed treatment at the first visit, while a substantial portion of moderate-risk children were successfully managed without an adaptation visit. Digital distraction, particularly when tailored to individual interests, enhanced cooperation and tolerance of procedures. Conclusions: The digital pre-visit tool enables early identification of behavioral risk and supports targeted application of digital distraction and sedation. This approach can improve child cooperation, reduce anxiety, optimize clinical efficiency, and contribute to positive early dental experiences. Full article

Background/Objectives: Q fever, caused by Coxiella burnetii, is typically treated with doxycycline, but its efficacy is limited in chronic cases and may be poorly tolerated. Systemic ciprofloxacin shows limited activity for acute Q fever. However, inhaled liposomal formulations may provide therapeutic benefit. Methods: Two inhaled ciprofloxacin formulations (Lipoquin^® and Apulmiq^®) were evaluated in an A/J mouse model of Q fever and compared with intraperitoneal ciprofloxacin and oral doxycycline. Initially, pharmacokinetic studies were performed to determine an appropriate dosing regimen for the inhaled ciprofloxacin formulations. A separate cohort of mice were then infected with C. burnetii and treated once daily via nebulisation with Lipoquin or Apulmiq, initiated at 24, 48, or 72 h post-challenge. Clinical signs, weight change, splenomegaly, bacterial burden, and lung histopathology were evaluated. Results: Pharmacokinetic analysis confirmed sustained lung concentrations of inhaled ciprofloxacin, supporting once-daily dosing. Inhaled Lipoquin and Apulmiq significantly reduced clinical signs, weight loss, splenomegaly, and pulmonary bacterial burden compared to untreated controls and doxycycline-treated mice. Histopathology revealed decreased lung inflammation and lesion severity following inhalational dosing. Systemic ciprofloxacin slightly reduced splenic bacterial burden but was less effective in controlling pulmonary infection. Conclusions: Inhaled liposomal ciprofloxacin demonstrated superior protection and reduced respiratory manifestations of Q fever compared to doxycycline and systemic ciprofloxacin. These findings suggest inhaled formulations may represent a viable alternative for the treatment of Q fever pneumonia. Further studies are needed to evaluate clinical applicability and long-term outcomes. Full article

Iron oxide particles (magnetite Fe₃O₄, hematite α-Fe₂O₃, and maghemite γ-Fe₂O₃) are prevalent constituents of atmospheric particulate matter (PM) and have gained increasing attention due to potential health implications. This scoping review provides a broad mapping of published in vivo and in vitro studies addressing the biological and toxicological effects of iron oxide particles across particle size fractions (PM10, PM2.5, PM1.0, and nanoscale) and exposure routes, including inhalation, intranasal instillation, and intravenous administration. As a scoping review, no formal risk-of-bias appraisal was conducted; however, studies were selected through predefined eligibility criteria and a structured screening workflow. Iron oxide exposure is consistently associated with oxidative stress and inflammatory responses, while mitochondrial dysfunction, genotoxicity, and neurological effects are frequently reported depending on particle characteristics and exposure context. Among studies with explicit crystalline phase identification, magnetite is most frequently associated with higher biological reactivity, whereas hematite and maghemite display more variable and context-dependent responses. Limited human evidence aligns with experimental findings, identifying magnetite-rich nanoparticles in neural and cardiovascular tissues alongside markers of oxidative and mitochondrial damage. Overall, this scoping review highlights dominant research trends, mechanistic pathways, and key knowledge gaps regarding iron oxide-containing PM, emphasizing the need for integrative approaches linking atmospheric particle characterization with toxicological research. Full article

Oxygen therapy is one of the most widely used interventions in critical care, yet it remains poorly individualized. Recent trials and meta-analysis suggest no mortality difference between conservative and liberal oxygen strategies, reinforcing the perception that dose does not matter within usual ranges. From this perspective, we argue that this apparent neutrality may largely reflect methodological and conceptual limitations, although true clinical equivalence in some patient populations remains plausible and cannot be excluded based on current evidence. Heterogeneous populations, overlapping oxygenation targets, and the absence of exposure metrics (time in hyperoxia, time in hypoxemia, and cumulative partial pressure of arterial oxygen/peripheral oxygen saturation curves) dilute phenotype-specific signals and force distinct physiological responses into a single pooled estimate. We propose a conceptual model in which oxygen behaves as a dose-dependent, time-dependent drug with phenotype-specific therapeutic windows, particularly in chronic hypercapnia, traumatic brain injury, sepsis, and early versus late acute respiratory distress syndrome. Building on this model, we outline a methodological agenda for precision oxygen trials: defining interventions by actual exposure, pre-specifying pathophysiological subgroups, adopting patient-centered core outcome sets, and using adaptive, target-range designs and individual patient data meta-analyses. For contemporary guidelines and research, the key question is no longer whether conservative or liberal oxygen therapy is superior on average, but how to match the right oxygenation range to the right intensive care unit phenotype at the right time. Moving from population-averaged comparisons to exposure-aware, phenotype-oriented strategies is essential if oxygen therapy is to become a truly precision intervention in critical care. Full article

Chronic exposure to heavy metals poses significant health risks. This study analyzed the concentrations of toxic (Cr, Pb, Cd, Ni) and essential (Cu, Zn, Se, Mn) elements in autopsy samples (the frontal pole area of the brain, the 6th intercostal space of the liver, and lungs (average of left and right lung samples) from 45 residents of South-Eastern Poland using ICP-MS. The aim was to determine the average body burden and organ-specific accumulation in a moderately industrialized region. HDBSCAN clustering revealed highly homogeneous elemental profiles, suggesting a unifying influence of local environmental factors. The liver acted as a metabolic hub, showing preferential sequestration (p < 0.0001) of essential elements (Zn, Se, Mn, Cu) regulated by homeostatic mechanisms. Toxic metals exhibited ‘metabolic trap’ patterns, particularly Cd and Pb in the liver and Cr in the lungs, due to their long biological half-lives. Strong positive correlations (Se–Zn, Se–Cu) indicated integrated antioxidant responses, while toxic pairs (Cr–Ni, Pb–Cd) suggested shared exposure pathways and molecular mimicry via transporters such as DMT1. Results confirmed long-term bioaccumulation, with toxic elements in the brain remaining below 0.25 µg/g. In the lungs, the accumulation hierarchy (Pb > Mn > Cd > Cr) reflected inhalation exposure. These findings emphasize the role of organ-specific sequestration in assessing long-term environmental exposure. Full article

Background: Carcinogenic, Mutagenic, and Reprotoxic (CMR) substances are among the most significant occupational health hazards in healthcare and research laboratories. Despite preventive measures and regulations, exposure assessment and risk management remain complex due to varied working practices, mixed exposures, and the lack of harmonized monitoring protocols. This systematic review investigates occupational exposure to CMR substances in laboratory and healthcare environments. Methods: Searches were conducted in PubMed, Scopus, and Web of Science up to February 2025 using tailored keyword strategies. Studies published between 2020 and 2025 reporting exposure assessment, monitoring, and/or risk management of CMR chemicals were included; non-English papers and irrelevant studies were excluded. Titles/abstracts and full texts were screened independently by two reviewers with arbitration by a third. Risk of bias was assessed by three authors who independently evaluated each study. A narrative synthesis with frequency tables was performed; no meta-analysis was conducted. Results: Of 446 screened records, 50 studies were included. Formaldehyde (25 studies) and antineoplastic drugs (18 studies) were most frequently examined. Healthcare settings—e.g., hospital pharmacies, oncology wards, and pathology laboratories—were predominant, while research laboratories were underrepresented. Inhalation was the main exposure route for formaldehyde, whereas dermal uptake and surface contamination predominated for antineoplastic drugs. Monitoring methods included air sampling, surface wipe testing, and biological assays; preventive strategies varied and were inconsistently applied. Most included studies involved environmental monitoring and did not report participant numbers, so a total number of participants cannot be aggregated; for the main outcomes, participant counts were often not available. Limitations of the evidence include marked heterogeneity across settings, matrices, analytical methods, and reporting units, which precluded meta-analysis, as well as imprecision and incomplete reporting in several studies. Conclusions: Findings reveal persistent gaps in harmonized exposure limits, monitoring standards, and long-term health surveillance, underscoring the need for comprehensive prevention strategies. This review was not registered and did not receive any external funding. Full article

Brucella infection is frequently acquired by inhalation, but the pathogen disseminates systemically from the lungs. However, little is known about the interaction of Brucella spp. with the airways. Using a 3D air-exposed organotypic human bronchial tissue model (polarized 16HBE14o- bronchial epithelial cells grown over a collagen matrix containing MRC-5 lung fibroblasts), we analyzed Brucella abortus replication, translocation and cytokine responses over prolonged post-infection times. Apically inoculated B. abortus invaded, replicated and persisted during the whole follow-up (16 days) within the bronchial tissue without inducing cytotoxicity. Viable bacteria were also detected in the conditioned medium (CM) since day five post-infection, indicating release from the basolateral side. In parallel experiments, no invasion or bacterial release was detected for Escherichia coli. The levels of IL-6, IL-8 and MCP-1 were increased in CM from Brucella-infected 3D cultures and in monocultures of polarized bronchial epithelial cells or lung fibroblasts. Collagenase/gelatinase activity was increased in 3D cultures and MRC-5 monocultures. Infection transference from bronchial cells to lung fibroblasts was documented using monocultures. An immune cross-talk was detected, as cytokine levels were increased in fibroblasts stimulated with bronchial CM, and vice versa. These results suggest that the bronchial mucosa can sustain B. abortus persistence, replication and dissemination, and that it induces a proinflammatory response to which both epithelial cells and fibroblasts contribute. Full article

Inhaled Treprostinil is the primary treatment of pulmonary hypertension related to interstitial lung disease (PH-ILD). Despite treatment effectiveness in clinical trials, the real-world safety and tolerability of this therapy remains unclear. We conducted a multicenter, retrospective review of adults with PH-ILD who were prescribed inhaled treprostinil. We assessed clinical outcomes, 6 min walk distance (6MWD) and changes in natriuretic peptides (BNP, NT-proBNP), as well as medication tolerance. Eighty-three patients met the inclusion criteria. The 6MWD data was collected but a limited number of patients had results within close proximity to initiation of inhalational treprostinil with only seven patients having assessments within the 3 months prior to initiation as well as 3 months post therapy. Limited 6MWD data is likely due, in part, to coinciding with the COVID pandemic, limiting face-to-face interactions and exercise testing. The majority of our subjects, 63%, had an absolute improvement in their BNP level, over a mean duration of 170 days. However, no significant difference was detected between baseline and follow-up natriuretic peptide levels. Adherence was assessed and the majority (77%) of patients remained on therapy at the time of censoring, with three-quarters (75%) meeting the target dose. Of the 15 patients intolerant to nebulized treprostinil who were transitioned to a dry powder inhaler, the majority (87%) were able to tolerate the other formulation. The medication was well-tolerated with a large percentage of patients remaining on therapy indefinitely and reaching the targeted therapeutic dose. Full article