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Recent advancements in in vitro transcribed mRNA (IVT-mRNA) vaccine manufacturing have attracted considerable interest as advanced methods for combating viral infections. The respiratory mucosa is a primary target for pathogen attack, but traditional intramuscular vaccines are not effective in generating protective ion mucosal surfaces. Mucosal immunization can induce both systemic and mucosal immunity by effectively eliminating microorganisms before their growth and development. However, there are several biological and physical obstacles to the administration of genetic payloads, such as IVT-mRNA and DNA, to the pulmonary and nasal mucosa. Nucleic acid vaccine nanocarriers should effectively protect and load genetic payloads to overcome barriers i.e., biological and physical, at the mucosal sites. This may aid in the transfection of specific antigens, epithelial cells, and incorporation of adjuvants. In this review, we address strategies for delivering genetic payloads, such as nucleic acid vaccines, that have been studied in the past and their potential applications.
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Imunidade nas Mucosas , Nanopartículas , Vacinação , Humanos , Animais , Vacinação/métodos , Vacinas de DNA/imunologia , Vacinas de DNA/administração & dosagem , Vacinas Baseadas em Ácido Nucleico/imunologia , Vacinas Baseadas em Ácido Nucleico/genética , Vacinas Baseadas em Ácido Nucleico/administração & dosagemRESUMO
Bacterial biofilms are organized heterogeneous assemblages of microbial cells encased within a self-produced matrix of exopolysaccharides, extracellular DNA and proteins. Over the last decade, more and more biofilm-associated proteins have been discovered and investigated. Furthermore, omics techniques such as transcriptomes, proteomes also play important roles in identifying new biofilm-associated genes or proteins. However, those important data have been uploaded separately to various databases, which creates obstacles for biofilm researchers to have a comprehensive access to these data. In this work, we constructed BBSdb, a state-of-the-art open resource of bacterial biofilm-associated protein. It includes 48 different bacteria species, 105 transcriptome datasets, 21 proteome datasets, 1205 experimental samples, 57,823 differentially expressed genes (DEGs), 13,605 differentially expressed proteins (DEPs), 1,930 'Top 5% differentially expressed genes', 444 'Threshold-based DEGs' and a predictor for prediction of biofilm-associated protein. In addition, 1,781 biofilm-associated proteins, including annotation and sequences, were extracted from 942 articles and public databases via text-mining analysis. We used E. coli as an example to represent how to explore potential biofilm-associated proteins in bacteria. We believe that this study will be of broad interest to researchers in field of bacteria, especially biofilms, which are involved in bacterial growth, pathogenicity, and drug resistance. Availability and implementation: The BBSdb is freely available at http://124.222.145.44/#!/.
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Proteínas de Bactérias , Biofilmes , Biofilmes/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Bactérias/genética , Bactérias/metabolismo , Bactérias/classificação , Transcriptoma , Proteoma , Escherichia coli/genética , Escherichia coli/metabolismo , Biologia Computacional/métodosRESUMO
This comprehensive review analysis examines the domain of composite thermoelectric materials that integrate nanoparticles, providing a critical assessment of their methods for improving thermoelectric properties and the procedures used for their fabrication. This study examines several approaches to enhance power factor and lattice thermal conductivity, emphasizing the influence of secondary phases and structural alterations. This study investigates the impact of synthesis methods on the electrical characteristics of materials, with a particular focus on novel techniques such as electrodeposition onto carbon nanotubes. The acquired insights provide useful guidance for the creation of new thermoelectric materials. The review also compares and contrasts organic and inorganic thermoelectric materials, with a particular focus on the potential of inorganic materials in the context of waste heat recovery and power production within industries. This analysis highlights the role of inorganic materials in improving energy efficiency and promoting environmental sustainability.
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OBJECTIVE: To compare the susceptibility of colistin by two methods in extensive drug-resistant (XDR) Gram-negative isolates from ICU patients. STUDY DESIGN: Cross-sectional comparative analysis. Place and Duration of the Study: Department of Microbiology, Combined Military Hospital Karachi, Pakistan, from August 2022 to February 2023. METHODOLOGY: A total of 100 clinical specimens received from the intensive care unit yielded growth of extensively drug-resistant gram-negative bacteria, which were evaluated for polymyxin E susceptibility. The agar dilution method was compared with the reference broth microdilution (BMD) method. Minimum inhibitory concentration (MIC) was noted for both methods. RESULTS: Comparison of the MIC method by agar dilution showed a 90% correlation with the reference method of broth microdilution. With MICs within the acceptable range of the clinical and laboratory standards institute (CLSI) recommendations, 89 isolates were susceptible to colistin, whereas only 11 remained resistant. Polymyxin E's MIC 50 and MIC 90 were determined to be 1 and 2 µg/ml, respectively, with 97% susceptibility. CONCLUSION: Agar dilution susceptibility method can be used for screening purposes for the susceptibility testing of polymyxin E. This method is reliable and can easily identify the heteroresistance. KEY WORDS: Extensively drug-resistant, Broth microdilution, Multidrug-resistant, Agar dilution, Minimum inhibitory concentration, Colony forming unit.
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Antibacterianos , Colistina , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , Unidades de Terapia Intensiva , Testes de Sensibilidade Microbiana , Colistina/farmacologia , Humanos , Testes de Sensibilidade Microbiana/métodos , Antibacterianos/farmacologia , Estudos Transversais , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Paquistão , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológicoRESUMO
Conventional geodetic methods rely on point measurements, which have drawbacks for detecting and tracking geologic disasters at specific locations. In this study, the time series Interferometric Synthetic Aperture Radar (InSAR) approach was incorporated to estimate non-linear surface deformation caused by tectonic, shoreline reclamation, and other anthropogenic activities in economically important urban regions of Pakistan's southern coast, which possesses around 270 km. The shoreline is extended from the low-populated area on the premises of the Hub River in the west to the highly populated Karachi City and Eastern Industrial Zone, where we collected the Sentinel-1A C-band data from 2017 to 2023 to address urban security and threats to human life and property. The main advantage of opting for the non-linear persistent scatterer interferometric SAR (PSInSAR) approach for this study is that it exposes minute movements without any prior consideration of conventional monitoring techniques, making it valid in continuously varying regions. An average vertical displacement range of - 170 to + 82 mm per year was found, which was used to investigate the potential correlation with the most effective causative parameters of deformation. The densely populated areas of the study area experience an annual subsidence of 170 mm, and the less populated western region experiences an uplift of 82 mm annually. Land deformation varies along the coast of the study area, where the eastern region is highly reclaimed and is affected by erosion. Groundwater table-depleting regions experienced high levels of land subsidence, and tectonic activities controlled vertical displacement in the region. Major variation was detected after an earthquake occurred along fault lines. This study was designed because a non-linear approach is required to address ground movement activities acutely, and it will make it possible to plan surface infrastructure and handle issues brought on by subsidence more effectively.
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Aims: This proof-of-concept study sought to evaluate changes in heart rate (HR) obtained from a consumer wearable device and compare against implantable loop recorder (ILR)-detected recurrence of atrial fibrillation (AF) and atrial tachycardia (AT) after AF ablation. Methods and results: REMOTE-AF (NCT05037136) was a prospectively designed sub-study of the CASA-AF randomized controlled trial (NCT04280042). Participants without a permanent pacemaker had an ILR implanted at their index ablation procedure for longstanding persistent AF. Heart rate and step count were continuously monitored using photoplethysmography (PPG) from a commercially available wrist-worn wearable. Photoplethysmography-recorded HR data were pre-processed with noise filtration and episodes at 1-min interval over 30â min of HR elevations (Z-score = 2) were compared with corresponding ILR data. Thirty-five patients were enrolled, with mean age 70.3 ± 6.8 years and median follow-up 10 months (interquartile range 8-12 months). Implantable loop recorder analysis revealed 17 out of 35 patients (49%) had recurrence of AF/AT. Compared with ILR recurrence, wearable-derived elevations in HR ≥ 110 beats per minute had a sensitivity of 95.3%, specificity 54.1%, positive predictive value (PPV) 15.8%, negative predictive value (NPV) 99.2%, and overall accuracy 57.4%. With PPG-recorded HR elevation spikes (non-exercise related), the sensitivity was 87.5%, specificity 62.2%, PPV 39.2%, NPV 92.3%, and overall accuracy 64.0% in the entire patient cohort. In the AF/AT recurrence only group, sensitivity was 87.6%, specificity 68.3%, PPV 53.6%, NPV 93.0%, and overall accuracy 75.0%. Conclusion: Consumer wearable devices have the potential to contribute to arrhythmia detection after AF ablation. Study Registration: ClinicalTrials.gov Identifier: NCT05037136 https://clinicaltrials.gov/ct2/show/NCT05037136.
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Background: The aim of this study was to examine the impact of different stages of dengue infection on immune cell counts among dengue patients and to compare them with cases of non-dengue febrile illness. Methods: The recruited patients were divided into two groups: the first group served as a control (n = 55), representing non-dengue febrile illness, and the second group was identified as dengue febrile illness (n = 149), which was further divided into three groups based on infection stage. Blood samples were collected from the selected patients and subjected to blood cell component analysis. To find IgG and IgM as well as the dengue virus non-structural antigen-1 (NS1), an immunochromatographic test (ICT) kit was utilized. Additionally, a hematological analyzer was used to determine complete blood cell counts (CBC). Data was thoroughly analyzed using Graph Pad Prism 6 software. The differences in means of different groups were calculated by applying the student's t-test. Results: The findings revealed the presence of severe leucopenia and thrombocytopenia at stages 1 and 2, accompanied by lymphopenia at stage 1. Group comparisons indicated that only teenagers exhibited a significantly lower white blood cell count compared to older individuals, while no significant differences were observed in lymphocytes, platelets, and monocytes across all age groups. Comparing different age groups of normal individuals to dengue-infected patients, the results unveiled that leucopenia was most severe in adults, followed by teenagers and children, with no significant difference in the elderly. Furthermore, adults showed the greatest degree of thrombocytopenia, followed by teens and kids, with the elderly showing the greatest degree of thrombocytopenia. Adults and teens showed extreme neutrophilia, whereas young children and the elderly showed no discernible abnormalities. Elderly patients experienced a marked decrease in monocyte count, a phenomenon not observed in other age groups. Conclusion: In conclusion both, leucopenia & thrombocytopenia, are most severe in stages 1 and 2, whereas neutrophilia & lymphopenia are predominantly severe in stage 1. These results imply that the consequences associated with dengue infection are more severe in the early stages and tend to ameliorate as the patient progresses toward recovery.
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BACKGROUND: Long-term clinical outcomes of catheter ablation (CA) compared to thoracoscopic surgical ablation (SA) to treat patients with long-standing persistent atrial fibrillation (LSPAF) are not known. OBJECTIVE: The purpose of this study was to compare the long-term (36-month) clinical efficacy, quality of life, and cost-effectiveness of SA and CA in LSPAF. METHODS: Participants were followed up for 3 years using implantable loop recorders and questionnaires to assess the change in quality of life. Intention-to-treat analyses were used to report the findings. RESULTS: Of the 115 patients with LSPAF treated, 104 (90.4%) completed 36-month follow-up [CA: n = 57 (95%); SA: n = 47 (85%)]. After a single procedure without antiarrhythmic drugs, 7 patients (12%) in the CA arm and 5 (11%) in the SA arm [hazard ratio 1.22; 95% confidence interval (CI) 0.81-1.83; P = .41] were free from atrial fibrillation/tachycardia (AF/AT) ≥30 seconds at 36 months. Thirty-three patients (58%) in the CA arm and 26 (55%) in the SA arm (hazard ratio 1.04; 95% CI 0.57-1.88; P = .91) had their AF/AT burden reduced by ≥75%. The overall impact on health-related quality of life was similar, with mean quality-adjusted life year estimates of 2.45 (95% CI 2.31-2.59) for CA and 2.32 (95% CI 2.13-2.52) for SA. Estimated costs were higher for SA (mean £24,682; 95% CI £21,746-£27,618) than for CA (mean £18,002; 95% CI £15,422-£20,581). CONCLUSION: In symptomatic LSPAF, CA and SA were equally effective at achieving arrhythmia outcomes (freedom from AF/AT ≥30 seconds and ≥75% burden reduction) after a single procedure without antiarrhythmic drugs. However, SA is significantly more costly than CA. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04280042.