-
The Canadian Journal of Infectious... 2024SARS-CoV-2 is a virus that affects the human immune system. It was observed to be on the rise since the beginning of 2020 and turned into a life-threatening pandemic.... (Review)
Review
SARS-CoV-2 is a virus that affects the human immune system. It was observed to be on the rise since the beginning of 2020 and turned into a life-threatening pandemic. Scientists have tried to develop a possible preventive and therapeutic drug against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and other related coronaviruses by assessing COVID-19-recovered persons' immunity. This study aims to review immunization against SARS-CoV-2, along with exploring the interventions that have been developed for the prevention of SARS-CoV-2. This study also highlighted the role of phototherapy in treating SARS-CoV infection. The study adopted a review approach to gathering the information available and the progress that has been made in the treatment and prevention of COVID-19. Various vaccinations, including nucleotide, subunit, and vector-based vaccines, as well as attenuated and inactivated forms that have already been shown to have prophylactic efficacy against the Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV, have been summarized. Neutralizing and non-neutralizing antibodies are all associated with viral infections. Because there is no specific antiviral vaccine or therapies for coronaviruses, the main treatment strategy is supportive care, which is reinforced by combining broad-spectrum antivirals, convalescent plasma, and corticosteroids. COVID-19 has been a challenge to keep reconsidering the usual approaches to regulatory evaluation as a result of getting mixed and complicated findings on the vaccines, as well as licensing procedures. However, it is observed that medicinal herbs also play an important role in treating infection of the upper respiratory tract, the principal symptom of SARS-CoV due to their natural bioactive composite. However, some Traditional Chinese Medicines contain mutagens and nephrotoxins and the toxicological properties of the majority of Chinese herbal remedies are unknown. Therefore, to treat the COVID-19 infection along with conventional treatment, it is recommended that herb-drug interaction be examined thoroughly.
PubMed: 38938549
DOI: 10.1155/2024/9952803 -
Frontiers in Pediatrics 2024Exercise induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young individuals, relevant to 5%-7% of young people. It is caused by...
BACKGROUND
Exercise induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young individuals, relevant to 5%-7% of young people. It is caused by paradoxical inspiratory adduction of laryngeal structures and diagnosed by continuous visualization of the larynx during high intensity exercise. Empirical data suggest that EILO consists of different subtypes that require different therapeutic approaches. Currently applied treatment approaches do not rest on randomized controlled trials (RCTs), and thus evidence-based guidelines cannot be established. This protocol describes the speech therapy treatment approach which is applied to EILO patients in a large prospective RCT called HelpILO.
METHODS AND ANALYSIS
Consenting patients consecutively diagnosed with EILO at Haukeland University Hospital are randomized into four treatment arms. Speech therapy is represented in two of these, provided in a structured manner based on general speech therapy principles and abdominal breathing, combined with experience obtained with these patients at our hospital during the last decades. The main outcome measure of HelpILO is changes of laryngoscopically visualized laryngeal adduction, rated at peak exercise before vs. after interventions, using a validated scoring system.
ETHICS AND DISSEMINATION
Despite widespread use of speech therapy in patients with EILO, this approach is insufficiently tested in RCTs, and the study is therefore considered ethically appropriate. The study will provide knowledge listed as a priority in a recent statement issued by major respiratory and laryngological societies and requested by clinicians and researchers engaged in this area. The results will be presented at relevant conferences, patient fora, and media platforms, and published in relevant peer reviewed international journals.
PubMed: 38938504
DOI: 10.3389/fped.2024.1356476 -
Open Veterinary Journal May 2024Computed tomography (CT) is the gold standard for diagnosing canine nasal diseases. However, it cannot easily detect minor abnormalities in inflammatory diseases because...
BACKGROUND
Computed tomography (CT) is the gold standard for diagnosing canine nasal diseases. However, it cannot easily detect minor abnormalities in inflammatory diseases because they are not accompanied by obvious morphological changes.
AIM
The present study aimed to compare the differences in normal CT findings of turbinate structure and mucosa between breeds to establish criteria for CT diagnosis of inflammatory diseases of the nasal cavity.
METHODS
CT data from 77 dogs of 5 breeds without nasal diseases were retrospectively studied. The nasal air percentage, which reflects the volume of the nasal turbinate structure and mucosa, was measured. The nasal turbinate mucosa was measured for contrast enhancement reflecting blood flow. Measurements were performed in the ventral and ethmoid turbinate (ET) regions. Comparisons were made between breeds and sections.
RESULTS
The air percentage in the ventral and ET regions was significantly different between breeds. Contrast enhancement was significantly different between breeds only in the ET. Moreover, different breeds had different correlations between body weight, age, nose length, and air percentage.
CONCLUSION
In this study, reference values for normal CT findings of the nasal structure and mucosa were obtained, taking into account the breed, measurement section, and patient factors. The results showed that the volume of the turbinate structure and contrast enhancement of nasal mucosa differed depending on the breed. The measured values also differed depending on the cross-sections and patient factors.
Topics: Animals; Dogs; Tomography, X-Ray Computed; Retrospective Studies; Female; Turbinates; Male; Nasal Mucosa; Dog Diseases; Nasal Cavity
PubMed: 38938433
DOI: 10.5455/OVJ.2024.v14.i5.13 -
Open Veterinary Journal May 2024The intramuscular (IM) administration of 7.5-10 mg/kg of alfaxalone produces anesthetic effects that enable endotracheal intubation with mild cardiorespiratory...
BACKGROUND
The intramuscular (IM) administration of 7.5-10 mg/kg of alfaxalone produces anesthetic effects that enable endotracheal intubation with mild cardiorespiratory depression in dogs. However, the effects of IM co-administration of medetomidine, butorphanol, and alfaxalone on cardiorespiratory function under inhalation anesthesia have not been studied.
AIM
To assess the cardiorespiratory function following the IM co-administration of 5 μg/kg of medetomidine, 0.3 mg/kg of butorphanol, and 2.5 mg/kg of alfaxalone (MBA) in dogs anesthetized with sevoflurane.
METHODS
Seven intact healthy Beagles (three males and four females, aged 3-6 years old and weighing 10.0-18.1 kg) anesthetized with a predetermined minimum alveolar concentration (MAC) of sevoflurane were included in this study. The baseline cardiorespiratory variable values were recorded using the thermodilution method with a pulmonary artery catheter after stabilization for 15 minutes at 1.3 times their individual sevoflurane MAC. The cardiorespiratory variables were measured again following the IM administration of MBA. Data are expressed as median [interquartile range] and compared with the corresponding baseline values using the Friedman test and Sheff's method. A < 0.05 was considered statistically significant.
RESULTS
The intramuscular administration of MBA transiently decreased the cardiac index [baseline: 3.46 (3.18-3.69), 5 minutes: 1.67 (1.57-1.75) l/minute/m : < 0.001], respiratory frequency, and arterial pH. In contrast, it increased the systemic vascular resistance index [baseline: 5,367 (3,589-6,617), 5 minutes:10,197 (9,955-15,005) dynes second/cm/m : = 0.0092], mean pulmonary arterial pressure, and arterial partial pressure of carbon dioxide.
CONCLUSION
The intramuscular administration of MBA in dogs anesthetized with sevoflurane transiently decreased cardiac output due to vasoconstriction. Although spontaneous breathing was maintained, MBA administration resulted in respiratory acidosis due to hypoventilation. Thus, it is important to administer MBA with caution to dogs with insufficient cardiovascular function. In addition, ventilatory support is recommended.
Topics: Animals; Sevoflurane; Butorphanol; Medetomidine; Dogs; Pregnanediones; Male; Female; Injections, Intramuscular; Anesthetics, Inhalation; Heart Rate; Blood Pressure
PubMed: 38938419
DOI: 10.5455/OVJ.2024.v14.i5.20 -
Journal of Translational Medicine Jun 2024Monocyte-derived alveolar macrophages (Mo_AMs) are increasingly recognised as potential pathogenic factors for idiopathic pulmonary fibrosis (IPF). While scRNAseq...
BACKGROUND
Monocyte-derived alveolar macrophages (Mo_AMs) are increasingly recognised as potential pathogenic factors for idiopathic pulmonary fibrosis (IPF). While scRNAseq analysis has proven valuable in the transcriptome profiling of Mo_AMs, the integration analysis of multi-omics may provide additional dimensions of understanding of these cellular populations.
METHODS
We performed multi-omics analysis on 116 scRNAseq, 119 bulkseq and five scATACseq lung tissue samples from IPF. We built a large-scale IPF scRNAseq atlas and conducted the Monocle 2/3 as well as the Cellchat to explore the developmental path and intercellular communication on Mo_AMs. We also reported the difference in metabolisms, tissue repair and phagocytosis between Mo_AMs and tissue-resident alveolar macrophages (TRMs). To determine whether Mo_AMs affected pulmonary function, we projected clinical phenotypes (FVC%pred) from the bulkseq dataset onto the scRNAseq atlas. Finally, we used scATATCseq to uncover the upstream regulatory mechanisms and determine key drivers in Mo_AMs.
RESULTS
We identified three Mo_AMs clusters and the trajectory analysis further validated the origin of these clusters. Moreover, via the Cellchat analysis, the CXCL12/CXCR4 axis was found to be involved in the molecular basis of reciprocal interactions between Mo_AMs and fibroblasts through the activation of the ERK pathway in Mo_AMs. SPP1_RecMacs (RecMacs, recruited macrophages) were higher in the low-FVC group than in the high-FVC group. Specifically, compared with TRMs, the functions of lipid and energetic metabolism as well as tissue repair were higher in Mo_AMs than TRMs. But, TRMs may have higher level of phagocytosis than TRMs. SPIB (PU.1), JUNB, JUND, BACH2, FOSL2, and SMARCC1 showed stronger association with open chromatin of Mo_AMs than TRMs. Significant upregulated expression and deep chromatin accessibility of APOE were observed in both SPP1_RecMacs and TRMs.
CONCLUSION
Through trajectory analysis, it was confirmed that SPP1_RecMacs derived from Monocytes. Besides, Mo_AMs may influence FVC% pred and aggravate pulmonary fibrosis through the communication with fibroblasts. Furthermore, distinctive transcriptional regulators between Mo_AMs and TRMs implied that they may depend on different upstream regulatory mechanisms. Overall, this work provides a global overview of how Mo_AMs govern IPF and also helps determine better approaches and intervention therapies.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Macrophages, Alveolar; Monocytes; Male; Gene Expression Profiling; Female; Receptors, CXCR4; Middle Aged; Phenotype; Lung; Gene Expression Regulation
PubMed: 38937806
DOI: 10.1186/s12967-024-05398-y -
Journal of Translational Medicine Jun 2024Interstitial lung disease (ILD) is the primary cause of mortality in systemic sclerosis (SSc), an autoimmune disease characterized by tissue fibrosis. SSc-related ILD...
BACKGROUND
Interstitial lung disease (ILD) is the primary cause of mortality in systemic sclerosis (SSc), an autoimmune disease characterized by tissue fibrosis. SSc-related ILD (SSc-ILD) occurs more frequently in females aged 30-55 years, whereas idiopathic pulmonary fibrosis (IPF) is more prevalent in males aged 60-75 years. SSc-ILD occurs earlier than IPF and progresses rapidly. FCN1, FABP4, and SPP1 macrophages are involved in the pathogenesis of lung fibrosis; SPP1 macrophages demonstrate upregulated expression in both SSc-ILD and IPF. To identify the differences between SSc-ILD and IPF using single-cell analysis, clarify their distinct pathogeneses, and propose directions for prevention and treatment.
METHODS
We performed single-cell RNA sequencing on NCBI Gene Expression Omnibus (GEO) databases GSE159354 and GSE212109, and analyzed lung tissue samples across healthy controls, IPF, and SSc-ILD. The primary measures were the filtered genes integrated with batch correction and annotated cell types for distinguishing patients with SSc-ILD from healthy controls. We proposed an SSc-ILD pathogenesis using cell-cell interaction inferences, and predicted transcription factors regulating target genes using SCENIC. Drug target prediction of the TF gene was performed using Drug Bank Online.
RESULTS
A subset of macrophages activates the MAPK signaling pathway under oxidative stress. Owing to the lack of inhibitory feedback from ANNEXIN and the autoimmune characteristics, this leads to an earlier onset of lung fibrosis compared to IPF. During initial lung injury, fibroblasts begin to activate the IL6 pathway under the influence of SPP1 alveolar macrophages, but IL6 appears unrelated to other inflammatory and immune cells. This may explain why tocilizumab (an anti-IL6-receptor antibody) only preserves lung function in patients with early SSc-ILD. Finally, we identified BCLAF1 and NFE2L2 as influencers of MAPK activation in macrophages. Metformin downregulates NFE2L2 and could serve as a repurposed drug candidate.
CONCLUSIONS
SPP1 alveolar macrophages play a role in the profibrotic activity of IPF and SSc-ILD. However, SSc-ILD is influenced by autoimmunity and oxidative stress, leading to the continuous activation of MAPK in macrophages. This may result in an earlier onset of lung fibrosis than in IPF. Such differences could serve as potential research directions for early prevention and treatment.
Topics: Humans; Scleroderma, Systemic; Macrophages; Lung Diseases, Interstitial; Female; Male; Middle Aged; Adult; Idiopathic Pulmonary Fibrosis; Aged; Gene Expression Regulation; Single-Cell Analysis; Lung
PubMed: 38937794
DOI: 10.1186/s12967-024-05403-4 -
BMC Oral Health Jun 2024To examine the patterns of pretreatment facial soft tissue shape in orthodontic cases with premolar extraction using artificial intelligence (AI) and to investigate the... (Comparative Study)
Comparative Study
OBJECTIVE
To examine the patterns of pretreatment facial soft tissue shape in orthodontic cases with premolar extraction using artificial intelligence (AI) and to investigate the corresponding changes.
METHODS
One hundred and fifty-two patients who underwent orthodontic treatment with premolar extraction were enrolled. Lateral cephalograms were obtained before and after the treatment. For each record, the outlines of the nose-lip-chin profile and corresponding 21 cephalometric variables were extracted. The AI method classified pretreatment records into three subject groups based on the feature variables extracted from the outline. Dentoskeletal and soft tissue facial form changes observed after treatment were compared statistically (P < 0.05) between the groups using ANOVA. Multivariate regression models were used for each group.
RESULTS
Group 1 (n = 59) was characterized by Class II high-angle retrognathic mandible with an incompetent lip, group 2 (n = 55) by Class I malocclusion with retruded and thin lips, and group 3 (n = 38) by Class I malocclusion with an everted superior lip before treatment. The ratios of anteroposterior soft tissue to hard tissue movements in Group 1 were 56% (r = 0.64) and 83% (r = 0.75) for the superior and inferior lips, respectively, whereas those in Group 2 were 49% (r = 0.78) and 91% (r = 0.80), and 40% (r = 0.54) and 79% (r = 0.70), respectively, in Group 3.
CONCLUSIONS
The modes of facial form changes differed depending on the pre-treatment profile patterns classified by the AI. This indicates that the determination of the pre-treatment profile pattern can help in the selection of soft tissue to hard tissue movement ratios, which helps estimate the post-treatment facial profile with a moderate to high correlation.
Topics: Humans; Cephalometry; Face; Bicuspid; Tooth Extraction; Female; Male; Lip; Adolescent; Nose; Malocclusion, Angle Class I; Artificial Intelligence; Chin; Malocclusion, Angle Class II; Mandible; Tooth Movement Techniques; Child; Young Adult; Malocclusion
PubMed: 38937790
DOI: 10.1186/s12903-024-04512-2 -
NPJ Primary Care Respiratory Medicine Jun 2024The British Thoracic Society (BTS) and Scottish Intercollege Guidelines Network (SIGN), as well as National Institute for Health and Care Excellence (NICE), have... (Review)
Review
The British Thoracic Society (BTS) and Scottish Intercollege Guidelines Network (SIGN), as well as National Institute for Health and Care Excellence (NICE), have previously produced separate asthma guidance differing in some key aspects in diagnosis and management leading to confusion, potentially hampering guideline dissemination and uptake. While there are inherent challenges, the upcoming release of new joint BTS/SIGN/NICE asthma guidance presents an opportunity to assess guideline adoption and its impact on clinical practice. The use of prescription data via databases such as OpenPrescribing can be used as a surrogate for guideline adoption and potentially linked to clinical outcomes such as hospital episode statistics (HES). The potential recommendation for anti-inflammatory reliever therapy (AIR) and maintenance and reliever therapy (MART) with inhaled corticosteroid/formoterol combination therapy in the next iteration of UK asthma guidance will require the accurate coding for the respective therapeutic approaches on prescribing platforms in order to assess their impact in real-life clinical practice. This could then direct targeted measures to improve wider guidance adoption leading to better clinical care in asthma based on up to date evidence.
Topics: Humans; Asthma; Practice Guidelines as Topic; United Kingdom; Anti-Asthmatic Agents; Guideline Adherence; Adrenal Cortex Hormones
PubMed: 38937520
DOI: 10.1038/s41533-024-00379-6 -
Scientific Reports Jun 2024Exploring a novel approach to mental health technology, this study illuminates the intricate interplay between exteroception (the perception of the external world), and...
Exploring a novel approach to mental health technology, this study illuminates the intricate interplay between exteroception (the perception of the external world), and interoception (the perception of the internal world). Drawing on principles of sensory substitution, we investigated how interoceptive signals, particularly respiration, could be conveyed through exteroceptive modalities, namely vision and hearing. To this end, we developed a unique, immersive multisensory environment that translates respiratory signals in real-time into dynamic visual and auditory stimuli. The system was evaluated by employing a battery of various psychological assessments, with the findings indicating a significant increase in participants' interoceptive sensibility and an enhancement of the state of flow, signifying immersive and positive engagement with the experience. Furthermore, a correlation between these two variables emerged, revealing a bidirectional enhancement between the state of flow and interoceptive sensibility. Our research is the first to present a sensory substitution approach for substituting between interoceptive and exteroceptive senses, and specifically as a transformative method for mental health interventions, paving the way for future research.
Topics: Humans; Interoception; Female; Male; Adult; Young Adult; Acoustic Stimulation; Respiration; Photic Stimulation
PubMed: 38937475
DOI: 10.1038/s41598-024-63231-4 -
Nature Communications Jun 2024The genome of Mycobacterium tuberculosis encodes for a large repertoire of toxin-antitoxin systems. In the present study, MenT3 and MenT4 toxins belonging to MenAT...
The genome of Mycobacterium tuberculosis encodes for a large repertoire of toxin-antitoxin systems. In the present study, MenT3 and MenT4 toxins belonging to MenAT subfamily of TA systems have been functionally characterized. We demonstrate that ectopic expression of these toxins inhibits bacterial growth and this is rescued upon co-expression of their cognate antitoxins. Here, we show that simultaneous deletion of menT3 and menT4 results in enhanced susceptibility of M. tuberculosis upon exposure to oxidative stress and attenuated growth in guinea pigs and mice. We observed reduced expression of transcripts encoding for proteins that are essential or required for intracellular growth in mid-log phase cultures of ΔmenT4ΔT3 compared to parental strain. Further, the transcript levels of proteins involved in efficient bacterial clearance were increased in lung tissues of ΔmenT4ΔT3 infected mice relative to parental strain infected mice. We show that immunization of mice and guinea pigs with ΔmenT4ΔT3 confers significant protection against M. tuberculosis infection. Remarkably, immunization of mice with ΔmenT4ΔT3 results in increased antigen-specific T1 bias and activated memory T cell response. We conclude that MenT3 and MenT4 are important for M. tuberculosis pathogenicity and strains lacking menT3 and menT4 have the potential to be explored further as vaccine candidates.
Topics: Animals; Guinea Pigs; Mycobacterium tuberculosis; Mice; Bacterial Proteins; Tuberculosis; Female; Lung; Gene Deletion; Bacterial Toxins; Mice, Inbred C57BL; Tuberculosis Vaccines; Oxidative Stress; Virulence
PubMed: 38937463
DOI: 10.1038/s41467-024-49246-5