Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is known to cause annual epidemics of respiratory infections; however, the lack of specific treatment options for this disease poses a challenge. In light of this, there has been a concerted effort to identify small molecules that can effectively combat RSV. This article focuses on the mechanism of action of compound K142, which was identified as a primary screening leader in the earlier stages of the project. The research conducted demonstrates that K142 significantly reduces the intensity of virus penetration into the cells, as well as the formation of syncytia from infected cells. These findings show that the compound's interaction with the surface proteins of RSV is a key factor in its antiviral activity. Furthermore, pharmacological modeling supports that K142 effectively interacts with the F-protein. However, in vivo studies have shown only weak antiviral activity against RSV infection, with a slight decrease in viral load observed in lung tissues. As a result, there is a need to enhance the bioavailability or antiviral properties of this compound. Based on these findings, we hypothesize that further modifications of the compound under study could potentially increase its antiviral activity.

Metallization system as a part of thermal memory.

This study aims to substantiate the potential of using "classical" metallization systems as microelectronic thermal memory cells. An experimental simulation is used to demonstrate that thermal information can be stored in memory for a certain time and then read without distortion. The possibility of using thin metal films on single-crystal silicon wafers as thermal memory cells is discussed. An experimental parametric study of "recording" thermal pulses and the temperature dynamics after their interruption is performed. This study uses rectangular current pulses with an amplitude of (1 … 6) × 1010 A/m2 and a duration of up to 1 ms. The temperature dynamics of a "thermal cell" are oscillographically studied up to the critical conditions when the contact area and metal film start degrading. The conditions of interconnections overheating up to the circuit break are considered.

Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort.

The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.

Correction to: Vilnius Declaration on chronic respiratory diseases: multisectoral care pathways embedding guided self-management, mHealth and air pollution in chronic respiratory diseases.

An amendment to this paper has been published and can be accessed via the original article.

Injury affects coelomic fluid proteome of the common starfish, Asterias rubens.

Echinoderms, possessing outstanding regenerative capabilities, provide a unique model system for the study of response to injury. However, little is known about the proteomic composition of coelomic fluid, an important biofluid circulating throughout the animal's body and reflecting the overall biological status of the organism. In this study, we used LC-MALDI tandem mass spectrometry to characterize the proteome of the cell-free coelomic fluid of the starfish Asterias rubens and to follow the changes occurring in response to puncture wound and blood loss. In total, 91 proteins were identified, of which 61 were extracellular soluble and 16 were bound to the plasma membrane. The most represented functional terms were 'pattern recognition receptor activity' and 'peptidase inhibitor activity'. A series of candidate proteins involved in early response to injury was revealed. Ependymin, ß-microseminoprotein, serum amyloid A and avidin-like proteins, which are known to be involved in intestinal regeneration in the sea cucumber, were also identified as injury-responsive proteins. Our results expand the list of proteins potentially involved in defense and regeneration in echinoderms and demonstrate dramatic effects of injury on the coelomic fluid proteome.

Vilnius Declaration on chronic respiratory diseases: multisectoral care pathways embedding guided self-management, mHealth and air pollution in chronic respiratory diseases.

BACKGROUND: Over 1 billion people suffer from chronic respiratory diseases such as asthma, COPD, rhinitis and rhinosinusitis. They cause an enormous burden and are considered as major non-communicable diseases. Many patients are still uncontrolled and the cost of inaction is unacceptable. A meeting was held in Vilnius, Lithuania (March 23, 2018) under the patronage of the Ministry of Health and several scientific societies to propose multisectoral care pathways embedding guided self-management, mHealth and air pollution in selected chronic respiratory diseases (rhinitis, chronic rhinosinusitis, asthma and COPD). The meeting resulted in the Vilnius Declaration that was developed by the participants of the EU Summit on chronic respiratory diseases under the leadership of Euforea. CONCLUSION: The Vilnius Declaration represents an important step for the fight against air pollution in chronic respiratory diseases globally and has a clear strategic relevance with regard to the EU Health Strategy as it will bring added value to the existing public health knowledge.

Modeling absorption spectra for detection of the combustion products of jet engines by laser remote sensing.

The absorption spectra of exhaust gases (H2O, CO, CO2, NO, NO2, and SO2) and aerosol (soot and Al2O3) particles were modeled at different temperatures for the first time and suitable spectral ranges were determined for conducting laser remote sensing of the combustion products of jet engines. The calculations were conducted on the basis of experimental concentrations of the substances and the sizes of the aerosol particles. The temperature and geometric parameters of jet engine exhausts were also taken from the literature. The absorption spectra were obtained via the line-by-line method, making use of the spectral line parameters from the authors' own high-temperature databases (for NO2 and SO2 gases) and the HITEMP 2010 database, and taking into account atmospheric transmission. Finally, the theoretical absorption spectra of the exhaust gases were plotted at temperatures of 400, 700, and 1000 K, and the impact of aerosol particles on the total exhaust spectra was estimated in spectral ranges suitable for remote sensing applications.

BAL fluid cells and pulmonary function in different radiographic stages of newly diagnosed sarcoidosis.

PURPOSE: Sarcoidosis affected lungs detected in more than 90% of patients. The relationship between different stages of pulmonary sarcoidosis and pulmonary function tests (PFT) as well as bronchoalveolar lavage fluid (BALF) cells can be established. Geographic and ethnic factors are known to be linked to the specific characteristics of patients with sarcoidosis. The purpose of the study was to evaluate peculiarities of BALF cells pattern and pulmonary function tests at the time of the diagnosis of different radiographic types of sarcoidosis in a large group of Lithuanian sarcoid patients. MATERIAL AND METHODS: This is the prospective study of BALF cells and PFT of patients with newly diagnosed sarcoidosis. The study population consisted of 221 non-treated non-smoker patients. All patients underwent BAL and the majority of them underwent PFT. RESULTS: Comparing Stage I to Stage III groups, a slight increase in the macrophage and neutrophil count and a decrease of lymphocyte count was apparent. However, the leukocyte population difference was not statistically significant. We have observed significant increase of CD8 cell count, as well as a decrease of both the CD4 cell count and the CD4/CD8 ratio from Stage I to Stage III. We have determined statistically significant differences in all PFT parameters among the patient groups with different radiographic stages of sarcoidosis. The values of FVC, VC and TLC tended to decrease with an elevation of BALF neutrophils and/or eosinophils count. However BALF cells did not correlate well with PFT indices. CONCLUSIONS: In newly diagnosed sarcoid patients, BALF cell and PFT markers depend on the sarcoidosis stage.

Significance of bronchoscopic lung biopsy in clinical practice.

PURPOSE: At present bronchoscopic lung biopsy (BLB) is widely used to diagnose various lung diseases. However placing of BLB in the diagnostic sequence of various clinical situations is not so clear. The purpose of the study was to evaluate the diagnostic value of BLB in a daily clinical practice. MATERIAL AND METHODS: The data obtained from the case records of all 304 patients who had undergone BLB since January 1996 to December 2007 at the Centre of Pulmonology and Allergology of Vilnius University Hospital Santariskiu klinikos (Vilnius, Lithuania) were examined. RESULTS: Most of indications for BLB were a peripheral lung nodule (40% of all the cases), dissemination in the lung (24% of all BLBs) and non-resolving pulmonary infiltrates (16.3% of all biopsies). Adequate lung tissue for histological examination was obtained in 85% of the cases. Based on the pathological diagnosis and findings of other diagnostic methods the final clinical diagnosis was verified for most of the patients. However, at least in 8% of the cases, the final clinical diagnosis was yet syndromic. Of all the BLBs, serious complications occurred in 8 (2.6%) patients. Clinically significant pneumothorax requiring chest tube treatment occurred in 5 (1.6%) of 304 patients. Severe bleeding occurred in 3 (1%) out of all BLBs. CONCLUSION: BLB is a relatively effective and safe method for diagnosing lung diseases. In most cases of the lung infiltrate, nodule, dissemination and diffuse changes, BLB is suitable to choose method for lung biopsy.