Search Results (94)

The use of implants in the trachea is increasing in respiratory diseases as an alternative to address pathological problems with airway obstruction. This article presents the design and development of a three-way cannula and its evaluation in a testbed capable of emulating the human breathing cycle. The new tracheal cannula allows airflow through a third duct (vertical one) towards the vocal folds, enabling phonation. The testbed assesses Total Lung Capacity (TLC) and endotracheal pressure by considering the cannula inside a replica of a trachea. The flow is generated by a mechanism composed of electronic elements, and the implementation of instruments for measuring pressure and lung capacity enables the visual and continuous collection of data. The three-way cannula offers improvements in airway capacity, with an average of up to 1.766 L of airflow and a pressure of 17.083 mbar. The airflow at the upper branch allows for improvement, enabling the patient to phonate even with the implant in place, while preserving patency due to the biocompatibility and elasticity of platinum silicone. Full article

Calreticulin is a highly conserved and multifunctional molecular chaperone ubiquitously expressed in humans and animals. Beyond its well-established roles in calcium homeostasis, protein folding, and immune regulation, recent studies in aquatic species have suggested a previously unrecognized antimicrobial function of calreticulin. These findings raise the question of whether calreticulin also exerts antibacterial activity in terrestrial mammals, which has not been systematically investigated to date. To address this knowledge gap, we successfully constructed and expressed recombinant goat calreticulin using the Pichia pastoris expression system, yielding a protein of over 99% purity that predominantly exists in dimeric form. Functional assays demonstrated that both recombinant goat and human calreticulin exhibited preliminary inhibitory activity against Escherichia coli, Salmonella typhimurium, and Pasteurella multocida. Calreticulin was capable of binding to these three bacterial species as well as bacterial lipopolysaccharides (LPS). Notably, in the presence of Ca²⁺, calreticulin induced bacterial aggregation, indicating a potential mechanism for limiting bacterial dissemination and proliferation. Given the high anatomical, genetic, and physiological similarity between goats and humans—particularly in respiratory tract structure and mucosal immune function—neonatal goats were selected as a relevant model for evaluating the in vivo antimicrobial efficacy of calreticulin. Accordingly, we established an intranasal infection model using Pasteurella multocida to assess the protective role of calreticulin against respiratory bacterial challenge. Following infection, calreticulin expression was markedly upregulated in the nasal mucosa, trachea, and lung tissues. Moreover, intranasal administration of exogenous calreticulin significantly alleviated infection-induced pathological injury to the respiratory system and effectively decreased bacterial loads in infected tissues. Collectively, this study systematically elucidates the antimicrobial activity of calreticulin in a mammalian model and highlights its potential as a natural immune effector, providing novel insights for the development of host-targeted antimicrobial strategies. Full article

Advancements in endovascular stent graft design have enabled the treatment of distal aortic arch pathologies. However, the length of the proximal landing zone remains a limitation, especially with vascular anomalies like an aberrant right subclavian artery (ARSA) posing additional challenges. A 78-year-old patient underwent computed tomography angiography (CTA), which revealed progressive enlargement of a distal aortic arch aneurysm located beyond an ARSA that coursed between the esophagus and trachea. Following evaluation by the multidisciplinary Aortic Team, a hybrid procedure was planned. A right carotid-to-ARSA bypass was performed and a Castor single-branched stent graft (CSBSG) was deployed in the aortic arch with its side branch directed into the left subclavian artery (LSA), thereby covering the origin of the ARSA. To prevent a type II endoleak, plug embolization of the ARSA origin was subsequently performed. CSBSG is a feasible treatment for distal aortic arch aneurysms, even in the presence of vascular anomalies such as ARSA. Full article

In computed tomography (CT)-based evaluation of the extent of cystic changes in the lungs of patients with cystic lung diseases, such as Lymphangioleiomyomatosis (LAM), there is a lack of a lung phantom containing air-filled cavities that mimic pulmonary cysts to calibrate the measurement of cystic volumes from CT scans. We describe an easy-to-replicate cystic lung phantom consisting of basic lung structures of a trachea and two lung compartments. The lung compartments contain air cavities of varying sizes to mimic cystic lesions. The lung compartments are made of a foam material recommended by NIST to simulate the radiodensity of human lung parenchyma. In tests performed on a clinical scanner, various structures in the lung phantom were correctly recognized by two types of lung analysis software. The resulting cystic volume measurements revealed the relationship between the size of the cysts and the accuracy of the measurement. The significant finding was that the volumes of individual cysts were underestimated for small cysts. The error increased with decreasing cyst sizes. Such underestimation has not been mentioned previously and deserves the attention of clinicians using CT scans to assess the cyst burden in the lungs, particularly in patients presenting with numerous small pulmonary cysts. Full article

Background and Clinical Significance: This article explores the complexity of large-cell neuroendocrine carcinoma (LCNEC) by presenting a clinical case involving a 17-year-old admitted for persistent wheezing, with no history of respiratory toxin exposure, a background of atopy, and a suspected diagnosis of bronchial asthma. Given the patient’s age and the nature of the symptoms, the condition was initially diagnosed as asthma, leading to the initiation of maximum inhalation therapy. Case Presentation: Despite proper adherence and correct administration, symptoms persisted, necessitating the use of oral corticosteroids. Imaging revealed an extensive inhomogeneous mass in the cervical esophagus and trachea, along with a similar tumor in the right hilum, prompting bronchoscopy. The diagnosis of LCNEC was confirmed through imaging, histopathological findings, and a detailed immunohistochemical profile. Initially misdiagnosed as adenoid cystic carcinoma, this case highlights the diagnostic challenges and the importance of rigorous evaluation. Conclusions: It emphasizes that recurrent wheezing in adolescents is not always indicative of asthma and requires careful differential diagnosis to uncover less common causes. Full article

Parainfluenza viruses are a common cause of respiratory illness in many species. In this study, experimental, alphavirus-derived RNA particle vaccines either with or without adjuvant were evaluated against porcine parainfluenza virus 1 (PPIV1) challenge and compared to live virus exposure. Groups of ten, three-week-old pigs were vaccinated intramuscularly with an adjuvanted RNA particle (RPAdj/C) or non-adjuvanted RP (RP/C) or administered an intranasal live exposure (LE/C) dose of PPIV1 at 0- and 21-days post vaccination (DPV) followed by challenge with PPIV1 at 40 DPV. In addition, two groups were included as non-vaccinated, non-challenged (NV/NC) and non-vaccinated, challenged (NV/C) controls. Intranasal virus exposure and RP vaccination, regardless of adjuvant, reduced PPIV1 shedding in nasal swabs by 5 days post inoculation (DPI). All vaccinated or exposed pigs seroconverted as shown by enzyme-linked immunosorbent assay and serum virus neutralization. The antibody isotype detected in bronchoalveolar lavage fluid (BALF) LE/C was predominantly IgA while RP vaccination induced an IgG response. Reduced PPIV1 antigen was observed in the LE/C, RP/C and RPAdj/C groups in lung, trachea, or nasal turbinate epithelium. Additionally, the RPAdj vaccine significantly reduced nasal shedding compared to NV/C pigs although not as much as LE/C pigs. These results suggest vaccination could mitigate PPIV1 infection in commercial systems. Full article

Objective: To investigate the effect of Lipopolysaccharide (LPS)-induced acute lung injury (ALI) on the pulmonary pharmacokinetics (PK) of a systemically administered antibody in mice. Method: The PK of a non-target-binding antibody was evaluated in healthy mice and mice with intratracheal instillation of 5 mg/kg LPS. The plasma, bronchoalveolar lavage (BAL), trachea, bronchi, and lung homogenate PK of the antibody were measured following intravenous administration of 5 mg/kg antibody dose. Noncompartmental analysis was performed to determine AUC values. Antibody concentrations in all biological matrices were quantified using qualified ELISA. The effect of ALI on BAL albumin and total protein concentrations was also determined. BAL protein concentrations were corrected for dilution using plasma urea concentrations. Results: Intratracheal instillation of LPS and the resultant ALI led to ~2–4-fold higher concentrations of albumin and proteins in the BAL. LPS-induced ALI also notably altered the pulmonary PK of the antibody. The effect of ALI on the antibody PK was time and tissue dependent. The trachea and bronchi showed ~1.7-fold and ~1.4-fold lower antibody exposure compared with the control group, but the BAL fluid exhibited ~4-fold increase in antibody exposure following LPS treatment. Most noticeable changes in antibody PK occurred 24 h after LPS administration, and the effect was temporary for the bronchi and trachea. However, the changes in lung homogenate and, more notably, in BAL persisted until the end of the experiment. Thus, our investigation suggests that due to the acute nature of ALI-induced pathophysiology and the changing severity of the disease, the dose and timing of antibody administration following ALI may need to be optimized based on the target site of action (e.g., bronchi, trachea, BAL, lung parenchyma, etc.) to maximize the therapeutic effect of the antibody. Conclusions: ALI may significantly affect pulmonary PK of systemically administered antibodies. Changes caused by ALI are time and tissue dependent, and hence, the timing and dose of antibody following ALI may need to be optimized to maximize the therapeutic effect of the antibody at the site of action. Full article

Rattus norvegicus (brown rat), a widely distributed rodent and common biomedical model, is a known reservoir for many zoonotic pathogens but has not been traditionally recognized as a host for influenza A virus (IAV). To evaluate their susceptibility, we intranasally inoculated Sprague-Dawley rats with various IAV subtypes, including H5Nx, H7N9, H9N2, H10N8 and the 2009 pandemic H1N1. All strains productively infected the rats, inducing seroconversion without overt clinical signs. While replication efficiency varied, all viruses caused significant lung injury with a preferential tropism for the upper respiratory tract. Investigation of receptor distribution revealed a predominance of α2,3-linked sialic acid (SA) in the nasal turbinates and trachea, whereas α2,6-linked SA was more abundant in the lungs. Notably, both receptor types coexisted throughout the respiratory tract, aligning with the observed tissue-specific replication patterns and broad viral infectivity. These findings demonstrate that rats are permissive hosts for multiple IAV subtypes, challenging their exclusion from IAV ecology. The asymptomatic yet pathogenic nature of infection, combined with the global synanthropy of rats, underscores their potential role as cryptic reservoirs in viral maintenance and transmission. This study highlights the need for expanded surveillance of rodents in influenza ecology to mitigate zoonotic risks. Full article

Background/Objectives: Acute upper respiratory tract infections (URIs) are defined as inflammatory diseases of the nose, sinuses, pharynx, larynx, or trachea. They are common in children. The prescription of antibiotics for the treatment of URIs became a relevant theme in the scientific literature in recent decades. One of the most important ways to deal with increasing antimicrobial resistance is rational antibiotic therapy. This study aimed to evaluate the tendencies of antibiotic prescribing practices for Lithuanian children with URIs from 2018 to 2022. We describe how many children with URIs were prescribed antibiotics, which antibiotics were used, and whether prescribing practices meet national guidelines. Methods: Secondary data, which were used in this observational study, were collected from the Lithuanian Compulsory Health Insurance Fund (CHIF) electronic records. The study population consisted of children aged between 0 and 18 years who visited their primary care doctors (pediatricians or family doctors) between January 2018 and December 2022 and were prescribed antibiotics for the treatment of URIs. Results: Between 2018 and 2022, there were 445,328 visits reported when antibiotics, which belong to the J01 group according to the Anatomical Therapeutic Chemical Classification (ATC), were prescribed to children aged 0–18. In more than half of the visits (51.70%), children aged 0–5 were consulted. Penicillins were mostly prescribed for the treatment of acute nasopharyngitis. Macrolides were mostly used to treat acute laryngitis and tracheitis. Of all penicillin-class antibiotics, the most popular choice was amoxycillin. The primary choice of cephalosporin was cefadroxil, and the primary choice of macrolide was clarithromycin. Conclusions: During the period of 2018–2022, the number of prescriptions for antibiotics for URTIs decreased, but prescriptions for penicillin-class antibiotics increased in a relative manner. The most common diagnoses during these visits were acute tonsillitis and acute pharyngitis, and most antibiotic prescriptions were for children in the 0–5 age group. If Lithuania’s National Recommendations on the Rational Use of Antibiotics were implemented during the analyzed period, the prescribing tendencies would not meet them. Full article

Mucociliary clearance, the ability of the respiratory tract to protect the integrity of the airways through the mechanical removal of potentially harmful substances, is of enormous importance during intensive care treatment. The present study aimed to evaluate the influence of clinically relevant inotropic agents on mucociliary clearance. The particle transport velocity (PTV) of isolated murine tracheae was measured as a surrogate for mucociliary clearance in the presence of dobutamine, epinephrine, and milrinone. Inhibitory substances were applied to elucidate the signal transduction cascades and the value and origin of calcium ions which provoke alterations in mucociliary clearance function. Dobutamine, epinephrine, and milrinone increased the PTV in a dose-dependent manner with half maximal effective concentrations of 75.7 nM, 87.0 nM, and 13.7 µM, respectively. After the depletion of intracellular calcium stores, no increase in PTV was observed after administering any of the three inotropic agents. While dobutamine and epinephrine activated β-adrenergic receptors, epinephrine used both the phospholipase C (PLC) and protein kinase A (PKA) pathway to promote the release of intracellular Ca²⁺. However, dobutamine primarily acted on the PKA pathway, having only a minor influence on the PLC pathway. The induced changes in PTV following milrinone administration required both the PKA and PLC pathway, although the PKA pathway was responsible for most of the induced changes. In conclusion, the common inotropic agents dobutamine, epinephrine, and milrinone increase murine PTV in a concentration-dependent manner and ultimately release Ca²⁺ from intracellular calcium stores, suggesting the function of changes in mucociliary clearance in the respiratory tract. Full article

The electrolarynx (EL) is a common device for voice reconstruction in laryngectomy patients, but its mechanical sound source generates significant radiation noise, affecting the naturalness and acceptability of the speech. The parametric acoustic array (PAA), which produces directionally propagated difference-frequency sound waves, presents a promising alternative for creating a more natural glottal-like voice source in the trachea while reducing radiation noise. In this study, we developed a tissue-mimicking phantom to simulate human neck tissue and used a single-transducer-based PAA platform to generate modulated ultrasound signals with glottal waveform characteristics. Ultrasonic microphones captured sound signals fromthe trachea and surrounding air, and signal processing was used to isolate the difference-frequency signals. The results demonstrated that difference-frequency signals were successfully detected in the phantom’s trachea, with time-domain waveforms and frequency spectra closely resembling the designed glottal waveform (Pearson correlation coefficient = 0.9438). Additionally, radiation noise produced by the PAA was significantly lower (23 dB, p < 0.0001) compared to the traditional EL. These findings demonstrate the potential of PAA for voice source reconstruction in laryngectomy patients and suggest its capacity to enhance speech rehabilitation outcomes. Further research is required to refine the frequency range and evaluate clinical applicability. Full article

As yet, no systematic review on commercial deep learning-based auto-segmentation (DLAS) software for breast cancer radiation therapy (RT) planning has been published, although NRG Oncology has highlighted the necessity for such. The purpose of this systematic review is to investigate the performances of commercial DLAS software packages for breast cancer RT planning and methods for their performance evaluation. A literature search was conducted with the use of electronic databases. Fifteen papers met the selection criteria and were included. The included studies evaluated eight software packages (Limbus Contour, Manteia AccuLearning, Mirada DLCExpert, MVision.ai Contour+, Radformation AutoContour, RaySearch RayStation, Siemens syngo.via RT Image Suite/AI-Rad Companion Organs RT, and Therapanacea Annotate). Their findings show that the DLAS software could contour ten organs at risk (body, contralateral breast, esophagus-overlapping area, heart, ipsilateral humeral head, left and right lungs, liver, and sternum and trachea) and three clinical target volumes (CTVp_breast, CTVp_chestwall, and CTVn_L1) up to the clinically acceptable standard. This can contribute to 45.4%–93.7% contouring time reduction per patient. Although NRO Oncology has suggested that every clinical center should conduct its own DLAS software evaluation before clinical implementation, such testing appears particularly crucial for Manteia AccuLearning, Mirada DLCExpert, and MVision.ai Contour+ as a result of the methodological weaknesses of the corresponding studies such as the use of small datasets collected retrospectively from single centers for the evaluation. Full article

Objective. Our objective was to assess the proportion of false-positive CHD cases at the first-trimester evaluation of the fetal heart, performed by experienced operators. Methods. This multicenter retrospective study included of pregnant women with suspicion of CHDs during first-trimester screening for aneuploidies. In all cases, the fetal heart assessments were performed by obstetricians with extensive experience in first-trimester scanning, following an extended protocol proposed by SIEOG national guidelines, which included an axial view of the fetal abdomen and chest to assess visceral situs and evaluation of the four-chamber view (4CV) and three-vessel trachea view (3VTV) with color Doppler. In all suspected cases, fetal echocardiography was offered within 16 and/or at 19–22 weeks’ gestation. Results. From a population of 4300 fetuses, 46 CHDs were suspected. Twenty-four cases were excluded from this analysis because the parents opted for early termination of the pregnancies due to associated structural and/or genetic anomalies. For the remaining 22, echocardiography was performed by 16 weeks in 14 cases (64%) and after 16 weeks in 8 cases. In 19 cases (86.4%), a fetal cardiologist confirmed the presence of a CHD. In three cases (13%), the cardiac anatomy was found to be normal at the fetal echocardiography and postnatally. Conclusions. This study shows that the proportion of false-positive cases at the first-trimester ultrasound examination of the fetal heart, performed by experienced operators, may carry a higher risk of false-positive diagnosis than expected. Therefore, this issue must be discussed in instances where a CHD is suspected at the first-trimester screening. Full article

Exercise-Induced Pulmonary Hemorrhage (EIPH) is a common pulmonary disease among racehorses, diagnosed by the detection of blood in the trachea after strenuous exercise or the presence of hemosiderophages in the bronchoalveolar lavage fluid (BALF). Although the latter is considered the most sensitive method to diagnose EIPH, it is perceived as a less practical and more invasive procedure compared to tracheal wash (TW) collection among racehorse trainers. The present retrospective study aimed to verify the agreement between Tracheal wash and BALF cytology in assessing EIPH in racehorses. For this purpose, cytological data from 172 patients regarding hemosiderophage percentage, hemosiderin score, and percentage of recent, intermediate, and old EIPH were reviewed, and the simplified Total Hemosiderin Score (sTHS) was calculated. Non-parametric statistical tests were used to assess the difference and the correlation between TW and BALF. The two cytological methods strongly agreed in evaluating EIPH in racehorses for hemosiderophage percentage (ρ = 0.89, p < 0.001), hemosiderin score (k = 0.63, p < 0.001), sTHS (ρ = 0.87, p < 0.001), percentage of recent EIPH (ρ = 0.95, p < 0.001), intermediate EIPH (ρ = 0.92, p < 0.001), and old EIPH (ρ = 0.85, p < 0.001). In conclusion, TW showed to be a reliable method, which might substitute BALF in assessing EIPH in racehorses. Full article

To evaluate the immunoprotective effect of bacterial biomimetic vesicles (BBVs) against avian pathogenic Escherichia coli (APEC), a ΔtolA J11 mutant strain was generated by deleting the tolA gene in the low pathogenic O78 serotype J11 strain. The total protein content of outer membrane vesicles (OMVs) derived from the ΔtolA J11 strain exhibited a sevenfold increase compared to the wild-type strain. Additionally, high-pressure homogenization technology was employed to produce BBVs, resulting in a sixfold increase in total protein content compared to spontaneously secreted OMVs from ΔtolA J11. The immunogenicity of both OMVs and BBVs was assessed through intranasal or intramuscular immunization in specific pathogen-free (SPF) chickens. Results demonstrated that intranasal immunization with OMVs or BBVs in chickens elicited specific IgY antibodies against APEC outer membrane proteins and specific sIgA antibodies in the nasal cavity and trachea, as well as a significant increase in the proliferation response of chicken peripheral blood lymphocytes. The bacterial load in the blood and various organs of the challenged chickens were significantly reduced, resulting in a 66.67% and 58.30% survival rate against a high pathogenic serotype O78 strain challenge, while the control group exhibited only a 16.67% survival rate. The intramuscular immunization with OMVs or BBVs in chickens only induced specific IgY antibodies, with a survival rate of only 33.33% for challenged chickens during the same period. Therefore, intranasal vaccination of the highly productive BBVs is capable of eliciting an immune response similar to that of OMVs and providing protection against APEC infection, thus offering innovative insights for the advancement of APEC vaccines. Full article