(1) Background: Stereological estimations significantly contributed to our anatomical and physiological understanding of the lung by providing an average distribution of measured parameters over the entire lung parenchyma. However, most structural lung diseases show a very inhomogeneous pattern of alterations. (2) Methods: We developed a novel protocol for the analysis of all pulmonary airspaces. Our pipeline starts with high-resolution synchrotron radiation-based X-ray tomographic microscopy (SRXTM) and consists of (i) image segmentation with the combination of the free machine-learning tool Ilastik and ImageJ and (ii) calculation of the airspace diameter distribution of an entire lung using a diameter map function. To evaluate the new pipeline, lungs from adult mice with cystic fibrosis (CF)-like lung disease (ENaC-transgenic mice) or mice with elastase-induced emphysema were compared to healthy controls. (3) Results: We were able to show the distribution of airspace diameters throughout the entire lung, as well as separately for the conducting airways and the gas-exchange area. In the pathobiological context, we observed an irregular widening of parenchymal airspaces in mice with CF-like lung disease and elastase-induced emphysema. Comparable results were obtained when analyzing lungs imaged with μCT, suggesting that our pipeline is applicable to different kinds of imaging modalities. (4) Conclusions: We conclude that the airspace diameter map is well suited for a detailed analysis of unevenly distributed structural alterations in chronic muco-obstructive lung diseases such as cystic fibrosis and COPD.

This study evaluated the effectiveness of an electronic system for managing drug-sensitive pulmonary tuberculosis patients in the Kyrgyz Republic. This was a cohort study using programmatic data. The study included patients registered on the paper-based system in 2019 and the electronic system between June 2021 and May 2022. Data was taken from 302 individuals from the electronic system for completeness and concordance in comparison with the paper-based system. The study showed that for most variables the completeness and concordance was 85.3%-93.0% and was lowest for non-mandatory fields such as medication side effects (26.8% vs 13.6%). No significant difference was observed in time taken from symptom onset to diagnosis and treatment initiation between the two systems. However, the electronic system had a significantly higher percentage of patients who initiated treatment on the same day of diagnosis (80.3% vs. 57.1%). The proportion with successful outcomes was similar in both groups, but the electronic system had a significantly lower proportion of patients with outcomes that were not evaluated or recorded (4.8% vs. 14.3%, p < 0.001). The study highlights the potential advantages of implementing an electronic TB register system for improving records. We advocate for similar studies in other regions in Kyrgyz Republic.

The efficacy of an intranasal (IN) bovine respiratory syncytial virus (BRSV) administered in the face of passive immunity was assessed. Pooled colostrum was administered by intubation to fifty (50) beef-dairy crossbred calves the day they were born. The calves were transported to a research facility and were blocked by age and sex and randomly assigned into two groups, a sham-vaccinated intranasally with a placebo (sterile water) or vaccinated with a tri-valent modified live viral (MLV) vaccine. The calves were 92 days old when vaccinated (day 0). The calves were challenged by aerosolized BRSV on day 80 and day 81 as a respiratory challenge. The study was terminated on day 88. Lung lesion scores (LLS) were significantly lower for calves vaccinated with tri-valent MLV vaccine than those for calves that were sham-vaccinated. Serum neutralization (SN) antibody against BRSV in calves vaccinated with the tri-valent MLV vaccine demonstrated an anamnestic response on day 88. After challenge, the calves sham-vaccinated with the placebo lost weight while those vaccinated with the tri-valent MLV vaccine gained weight. In this study colostrum-derived antibodies did not interfere with the immune response or protection provided by one dose of the tri-valent MLV vaccine.

Engineered nanomaterials (ENMs) are of significant relevance due to their unique properties, which have been exploited for widespread applications. Cerium oxide nanoparticles (CeO2-NPs) are one of most exploited ENM in the industry due to their excellent catalytic and multi-enzyme mimetic properties. Thus, toxicological effects of these ENMs should be further studied. Acute and subchronic toxicity of CeO2-NPs were assessed. First an in vitro multi-dose short-term (24h) toxicological assessment was performed in three different cell lines: A549 and Calu3, representing the lung tissue, and 3T3 as an interstitial tissue model. After that, a sub-chronic toxicity assessment (90 days) of these NPs was carried out on a realistic and well stablished reconstituted primary human airway epithelial model (MucilAir™), cultured at the Air-Liquid Interface (ALI), to study long-term effects of these particles. Results showed minor toxicity of CeO2-NPs in acute exposures. However, in subchronic exposures, cytotoxic and inflammatory responses were observed in the human airway epithelial model after 60 days of exposure to CeO2-NPs. These results suggest that acute toxicity approaches may underestimate the toxicological effect of some ENM, highlighting the need of subchronic toxicological studies in order to accurately assess the toxicity of ENM and their cumulative effects in the organism.

The outflow tract of crocodilians resembles that of birds and mammals as ventricular septation is complete. The arterial anatomy however, presents with a pulmonary trunk originating from the right ventricular cavum, and two aortae originating from either the right or left ventricular cavum. Mixing of blood in crocodilians cannot occur at ventricular level as in other reptiles, but instead takes place at aortic root level by a shunt, the Foramen of Panizza, the opening of which is guarded by two facing semilunar leaflets of both bicuspid aortic valves. Methods. Developmental stages of Alligator mississipiensis, Crocodilus niloticus and Caiman latirostris, have been studied. Results and Conclusions. The outflow tract septation complex can be divided into 2 components. The aorto-pulmonary septum divides the pulmonary trunk from both aortae, whereas the interaortic septum divides the systemic from the visceral aorta. Neural crest cells are most likely involved in the formation of both components. Remodeling of the endocardial cushions and both septa results in the formation of bicuspid valves in all three arterial trunks. The foramen of Panizza originates intracardially as a channel in the septal endocardial cushion.

Acute high altitude illnesses are of great concern for physicians and people traveling to high altitude. High Altitude Pulmonary Edema (HAPE) can be better understood through the Oxygen Transport Triad which involves the Pneumo-Dynamic Pump (Ventilation), the Hemo-Dynamic Pump (Heart and circulation), and Hemoglobin. The two pumps are the first physiologic response upon initial exposure to hypobaric hypoxia. Hemoglobin is the balancing energy-saving time-evolving equilibrating factor. The increased hemoglobin at high altitude reduces the percentage of dissolved oxygen in the arterial oxygen content with respect to sea level. At high altitude, the acid-base balance must be adequately interpreted using the high altitude Van-Slyke correction factors. Pulse-oximetry measurements during breath-holding at high altitude allow for the evaluation of high altitude diseases. The Tolerance to Hypoxia Formula shows that, paradoxically, the higher the altitude the more tolerance to hypoxia. All organisms adapt physiologically and optimally to a high-altitude environment to survive. Reduction of pulmonary hypertension in HAPE through oxygen administration results in a favorable outcome.

C-C motif chemokine ligand 2 (CCL2), also called monocyte chemoattractant protein-1 (MCP-1) is a key β-chemokine involved in the migration of monocytes and macrophages, playing a significant role in the inflammatory responses in the airways. We aimed to assess the serum levels of MCP-1/CCL2 in a pilot cross-sectional study of Bulgarian children with bronchial asthma (BA) and cystic fibrosis (CF). Forty-two children were recruited to the study as follows: twenty with BA, twelve with CF and ten healthy children. Serum MCP-1/CCL2 levels were measured using ELISA. We found higher serum level of MCP-1/CCL2 in children with BA (191.09±64.96 pg/ml) and CF (258.51±76.45 pg/ml) compared to healthy children (70.30±64.30 pg/ml, p=0.022, and p=0.068, respectively). Younger patients with BA had higher levels of MCP-1/CCL2, as well as children with CF, with levels decreasing gradually with age. We observed also higher levels of MCP-1/CCL2 in children with moderate to severe BA compared to mild BA. We documented the significantly higher level of MCP-1/CCL2 in children with these chronic pulmonary diseases than in healthy controls, which suggesting that investigation of serum MCP-1/CCL2 levels could turn out to be beneficial for the severity of the disease.

Backround: Thoracic trauma causes life-threatening organ injuries, ranging from simple abrasions to contusions of intrathoracic organs. In this study, we aimed to investigate the effects of bosentan on endothelin-1 (ET-1), hypoxia-inducible factor-1 (HIF-1), nuclear factor-kappa B (NF-κB), tumor necrosis factor (TNF)-α as inflammation markers, pro-oxidant antioxidant balance (PAB) and total antioxidant capacity (TAC) levels as oxidative stress parameters in lung tissues of rats in experimental model of pulmonary contusion (PC) induced by blunt thoracic trauma. Methods: Thirty-seven animals male Sprague-Dawley rats were divided into 5 groups. All 4 groups, except for the control group, were performed to PC. In the first group, C: control group (n=6) consisted of unprocessed and untreated. The second group, PC3 (n=8) underwent of 3 days PC performed. The third group, PC-B3 (n=8) received 100 mg/kg bosentan was given orally once a day for 3 days. The fourth group, PC7 group (n=7) underwent of 7 days PC performed, and the fifth group PC-B7 (n=8) received 100 mg/kg bosentan was given orally once a day for 7 days. While ET-1, NF-B, TNF-, and HIF-1 was measured by ELISA method, TAC and PAB by spectrophotometric in lung tissue samples. Results: ET-1, NF-B, TNF-, HIF-1, and PAB levels were higher, while TAC activities were lower in all groups compared with the control (p < 0.05). There was no significant difference in ET-1 and TNF-- levels between the PC-B3 and PC-B7 groups and the control group (p < 0.05) while NF-B, HIF-1, and PAB levels were still higher in both the PC-B3 and PC-B7 groups than in the control group. Bosentan treatment causes decreased ET-1, NF-B, TNF-, HIF-1, and PAB and increased TAC levels in comparison to the nontreated groups (p < 0.05). Conclusions: We found that the use of bosentan decreased the severity of oxidative stress in the lung and reduced the inflammatory reaction in rats with PC induced by blunt thoracic trauma. This suggests that bosentan may have protective effects on lung injury mechanisms by reducing hypoxia, inflammation and oxidative stress. If supported by similar studies, bosentan can be used in both pulmonary and emergency clinics to reduce ischemic complications, inflammation, oxidative stress in some diseases that may be accompanied by ischemia.

Cisplatin (CDDP) is a platinum-based drug effective against various cancers, including lung, bladder, prostate, ovarian, esophageal, stomach, and cervical cancer and malignant lymphoma. It plays a central role as the first choice in current anticancer therapy. However, CDDP causes serious side effects, such as neurological disorders, myelosuppression, and renal damage, because it is a small molecule indiscriminately distributed in normal tissues. Therefore, it is very important to prevent or attenuate CDDP toxicity. We hypothesized that liposomalization of CDDP could alleviate serious side effects. Therefore, this study aimed to evaluate the safety and efficacy of CDDP liposomes. A patient with multiple recurrent liver metastases from metastatic nasal carcinoma was administered CDDP liposomes with consent. Magnetic resonance imaging showed that the patient remained stable-diseased; however, no apparent side effects were observed, and blood draw data showed no worsening of renal function. Patients undergoing partial pancreatectomy and jejunoileal biliary anastomosis for biliary tract cancer who consented to receive CDDP liposomes demonstrated a partial response on angiographic computed tomography; however, they showed slight fatigue. To our knowledge, the present study is the first in Japan to suggest that liposomalization of CDDP may have anticancer effects while alleviating renal damage and bone marrow suppression.

Background: In chronic obstructive pulmonary disease (COPD), there are two known classifications for assessing what is called disease severity. One is the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, which is based on the post-bronchodilator value of FEV1 (% reference). The other is the STaging of Airflow obstruction by Ratio (STAR). Methods: We reanalyzed data from our outpatient cohort study, which included 141 participants with COPD from 2015 to 2023. We compared mortality and COPD-specific health status between the GOLD 1 to 4 groups and the STAR 1 to 4 groups. Results: By simple calculation, GOLD and STAR severity classes coincided in 75 participants (53.2%). The weighted Bangdiwala B value with linear weights was 0.775. The participants were observed for up to 95 months, with a median of 54 months. Death was confirmed in 29 participants (20.5%). In univariate Cox proportional hazards analyses, there was a significant difference in mortality between the GOLD 1 and GOLD 3+4 groups, with the GOLD 1 group used as the reference [Hazard Ratio 4.222 (95% CI 1.298 - 13.733), p=0.017]. However, there was no statistically significant predictive relationship between STAR 1 and STAR 2, or between STAR 1 and STAR 3+4. The St. George's Respiratory Questionnaire (SGRQ) Total and COPD Assessment Test (CAT) scores were significantly different between all GOLD groups, except for the CAT score between GOLD 1 and GOLD 2. The SGRQ Total and CAT scores were significantly different between STAR 1 and STAR 3+4, but not between STAR 1 and STAR 2. Conclusion: From the perspective of all-cause mortality and COPD-specific health status, the GOLD classification is more discriminative than STAR.

The study comprehensively evaluated the prognostic roles of PLR, NLR, MLR, BLR, and ELR in patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD). 619 patients with AECOPD and 300 healthy volunteers were retrospectively included into the study. The clinical characteristics containing laboratory findings of the AECOPD patients and the blood cell counts (CBCs) of the healthy volunteers were collected. Compared with the healthy volunteers, PLR, NLR, and MLR were elevated in COPD patients in stable condition, and were further ele-vated during exacerbation. ELR showed the opposite trend. PLR, NLR, and MLR were all posi-tively correlated with hospital LOS as well as CRP. In contrast, ELR was negatively correlated with hospital LOS as well as CRP. Elevated PLR, NLR, and MLR were all associated with more serious airflow limitation in AECOPD. Elevated PLR, NLR, and MLR were all associated with increased in-hospital mortality while Elevated ELR was associated with decreased in-hospital mortality in AECOPD. A nomogram was construct to predict in-hospital mortality in AECOPD. The nomo-gram had a C-index of 0.850 (95% CI: 0.799 – 0.901) with good predictive value and clinical ap-plicability. In summary, PLR, NLR, MLR, and ELR served as predictors for clinical outcomes in patients with AECOPD.