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MSystems Jun 2024Airway microbiota are known to contribute to lung diseases, such as cystic fibrosis (CF), but their contributions to pathogenesis are still unclear. To improve our...
Airway microbiota are known to contribute to lung diseases, such as cystic fibrosis (CF), but their contributions to pathogenesis are still unclear. To improve our understanding of host-microbe interactions, we have developed an integrated analytical and bioinformatic mass spectrometry (MS)-based metaproteomics workflow to analyze clinical bronchoalveolar lavage (BAL) samples from people with airway disease. Proteins from BAL cellular pellets were processed and pooled together in groups categorized by disease status (CF vs. non-CF) and bacterial diversity, based on previously performed small subunit rRNA sequencing data. Proteins from each pooled sample group were digested and subjected to liquid chromatography tandem mass spectrometry (MS/MS). MS/MS spectra were matched to human and bacterial peptide sequences leveraging a bioinformatic workflow using a metagenomics-guided protein sequence database and rigorous evaluation. Label-free quantification revealed differentially abundant human peptides from proteins with known roles in CF, like neutrophil elastase and collagenase, and proteins with lesser-known roles in CF, including apolipoproteins. Differentially abundant bacterial peptides were identified from known CF pathogens (e.g., ), as well as other taxa with potentially novel roles in CF. We used this host-microbe peptide panel for targeted parallel-reaction monitoring validation, demonstrating for the first time an MS-based assay effective for quantifying host-microbe protein dynamics within BAL cells from individual CF patients. Our integrated bioinformatic and analytical workflow combining discovery, verification, and validation should prove useful for diverse studies to characterize microbial contributors in airway diseases. Furthermore, we describe a promising preliminary panel of differentially abundant microbe and host peptide sequences for further study as potential markers of host-microbe relationships in CF disease pathogenesis.IMPORTANCEIdentifying microbial pathogenic contributors and dysregulated human responses in airway disease, such as CF, is critical to understanding disease progression and developing more effective treatments. To this end, characterizing the proteins expressed from bacterial microbes and human host cells during disease progression can provide valuable new insights. We describe here a new method to confidently detect and monitor abundance changes of both microbe and host proteins from challenging BAL samples commonly collected from CF patients. Our method uses both state-of-the art mass spectrometry-based instrumentation to detect proteins present in these samples and customized bioinformatic software tools to analyze the data and characterize detected proteins and their association with CF. We demonstrate the use of this method to characterize microbe and host proteins from individual BAL samples, paving the way for a new approach to understand molecular contributors to CF and other diseases of the airway.
PubMed: 38934598
DOI: 10.1128/msystems.00929-23 -
Heliyon Jun 2024Current biofilm modelling of the opportunistic pathogen, (PA) in people with cystic fibrosis (PwCF) is limited in its ability to mimic the complexities of the cystic...
Current biofilm modelling of the opportunistic pathogen, (PA) in people with cystic fibrosis (PwCF) is limited in its ability to mimic the complexities of the cystic fibrosis (CF) lung environment. Recent adaptations of the Microbial Identification after Passive CLARITY Technique (MiPACT) in CF research have allowed for the direct imaging of PA biofilm spatial organization and structure in expectorated sputum. Here, we performed a comparative analysis of and within patient () measures of PA biofilms using sputa from new onset infected children with CF. MiPACT-fluorescent hybridization (FISH) and fluorescent anti-Psl monoclonal antibody (mAb) staining was performed to directly visualize PA and Psl (exopolysaccharide in PA biofilm matrix) in 11 CF sputum specimens. Corresponding PA isolates, recovered from the same sputum samples, were grown as biofilms in a glass slide chamber model, then visualized by fluorescent live-cell and anti-Psl mAb staining. We observed that PA biovolume, aggregation and Psl antibody binding (normalized per PA biovolume) in CF sputum did not correlate with the model, although a trend towards significance in the biovolume relationship was observed with the addition of sputum supernatant to the model.
PubMed: 38933957
DOI: 10.1016/j.heliyon.2024.e32424 -
Infection and Drug Resistance 2024Carbapenem-resistant (CRKP) infections are a great threat to public health worldwide. Ceftazidime-avibactam (CZA) is an effective -lactam/-lactamase inhibitors against...
BACKGROUND
Carbapenem-resistant (CRKP) infections are a great threat to public health worldwide. Ceftazidime-avibactam (CZA) is an effective -lactam/-lactamase inhibitors against CRKP. However, reports of resistance to CZA, mainly caused by carbapenemase (KPC) variants, have increased in recent years. In this study, we aimed to describe the resistance characteristics of KPC-12, a novel KPC variant identified from a CZA resistant .
METHODS
The YFKP-97 collected from a patient with respiratory tract infection was performed whole-genome sequencing (WGS) on the Illumina NovaSeq 6000 platform. Genomic characteristics were analyzed using bioinformatics methods. Antimicrobial susceptibility testing was conducted by the broth microdilution method. Induction of resistant strain was carried out in vitro as previously described. The killing assay was used to evaluate the pathogenicity of strains, and the conjugation experiment was performed to evaluate plasmid transfer ability.
RESULTS
Strain YFKP-97 was a multidrug-resistant clinical ST11-KL47 confers high-level resistance to CZA (16/4 μg/mL). WGS revealed that a KPC variant, KPC-12, was carried by the IncFII (pHN7A8) plasmids (pYFKP-97_a and pYFKP-97_b) and showed significantly decreased activity against carbapenems. In addition, there was a dose-dependent effect of on its activity against ceftazidime. In vitro inducible resistance assay results demonstrated that the KPC-12 variant was more likely to confer resistance to CZA than the KPC-2 and KPC-3 variants.
DISCUSSION
Our study revealed that patients who was not treated with CZA are also possible to be infected with CZA-resistant strains harbored a novel KPC variant. Given that the transformant carrying was more likely to exhibit a CZA-resistance phenotype. Therefore, it is important to accurately identify the KPC variants as early as possible.
PubMed: 38933778
DOI: 10.2147/IDR.S465699 -
Archives of Rheumatology Jun 2024This study aimed to analyze the risk factors for mortality of idiopathic inflammatory myopathy (IIM) patients admitted with interstitial lung disease (ILD) to guide...
OBJECTIVES
This study aimed to analyze the risk factors for mortality of idiopathic inflammatory myopathy (IIM) patients admitted with interstitial lung disease (ILD) to guide rapid and accurate judgment of clinical prognosis.
PATIENTS AND METHODS
This retrospective, single-center cohort study was conducted with 135 participants (37 males, 98 females; mean age: 54.8±11.1 years; range, 24 to 85 years) between June 1, 2016, and June 30, 2021. The participants were categorized into the survival group (n=111) and nonsurvivors (n=24) according to whether they survived during the one-year follow-up. The independent risk factors for mortality in one year after discharge were analyzed. Receiver operating characteristic curve analysis was used to determine the accuracy of oxygenation index at baseline combined with pulmonary infection (PI) at follow-up to indicate death in IIM-ILD patients.
RESULTS
Compared to the survival group, nonsurvivors were older (p=0.006) and had a higher proportion of anti-MDA5 (melanoma differentiation-associated protein 5) positivity (p<0.001). The ILD duration was shorter (p=0.006), the oxygenation index was lower (p<0.001), and the intensive care unit occupancy rate (p<0.001) and ventilator utilization rate (p<0.001) were elevated in nonsurvivors compared to the survival group. Oxygenation index at baseline (odds ratio [OR]=1.021, 95% confidence interval [CI]: 1.001-1.023, p=0.040) and PI (clinical judgment) at follow-up (OR=16.471, 95% CI: 1.565-173.365, p=0.020) were found as independent risk factors for death in the year after discharge in IIM inpatients with ILD. An oxygenation index ≤279 mmHg at baseline combined with PI at follow-up exhibited a promising predictive value for all-cause death in IIM-ILD patients within one year.
CONCLUSION
Oxygenation index at baseline and PI during follow-up were independent risk factors for death of IIM-ILD patients within one year after discharge. Patients with an oxygenation index ≤279 mmHg at baseline had an increased risk of death once they developed PI during the one-year follow-up.
PubMed: 38933718
DOI: 10.46497/ArchRheumatol.2024.10418 -
Frontiers in Pharmacology 2024We conducted an overview to assess immune adverse effects associated with the COVID-19 vaccine, guiding safer choices and providing evidence-based information to...
BACKGROUND
We conducted an overview to assess immune adverse effects associated with the COVID-19 vaccine, guiding safer choices and providing evidence-based information to clinicians.
METHODS
Forty-three studies on adverse effects of vaccines were reviewed from PubMed, Embase, and Web of Science. Single-arm meta-analyses estimated summary effects, incidence, presentation, etc. An overview using single-arm meta-analysis and reported the findings following the guidelines outlined in the 'Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) specifically focusing on myocarditis and thrombosis. After screening 2,591 articles, 42 studies met the inclusion criteria. Methodological quality was evaluated using AMSTAR 2. Disagreements were resolved via consensus. Data analysis utilized a random-effects model in R software to estimate incidence rates of selected adverse events.
RESULTS
After removing 1,198 duplicates and screening out irrelevant articles from a total of 2,591, we included 42 studies. Adverse reactions to vaccinations include myocarditis, thrombosis, skin reactions, GBS, etc. thrombosis and myocarditis are the most dangerous diseases associated with vaccination. Myocarditis occurred in 6% of Vector vaccine recipients, compared to 61% of mRNA vaccine recipients. Thrombosis was more common after Vector vaccination (91%) than after mRNA vaccination (9%). Furthermore, eight studies conducted anti-PF4 antibody tests and yielded a positivity rate of 67%. Meta-analysis showed that among all patients with Vaccine-induced Thrombotic Thrombocytopenia, cerebral venous sinus thrombosis occurred in 66%, and intracranial hemorrhage occurred in 43%. The rates of deep vein thrombosis and pulmonary thromboembolism in vaccinated patients were 13% and 23%, respectively, with a pooled case fatality rate of 30%.
CONCLUSION
The results of this overview indicate the majority of adverse reactions are self-limiting and require minimal intervention, while rare occurrences such as myocarditis and thrombosis pose a potentially fatal threat.
PubMed: 38933672
DOI: 10.3389/fphar.2024.1308768 -
Frontiers in Rehabilitation Sciences 2024Cough is a powerful, protective expulsive behavior that assists in maintaining respiratory health by clearing foreign material, pathogens, and mucus from the airways.... (Review)
Review
Cough is a powerful, protective expulsive behavior that assists in maintaining respiratory health by clearing foreign material, pathogens, and mucus from the airways. Therefore, cough is critical to survival in both health and disease. Importantly, cough protects the airways and lungs from both antegrade (e.g., food, liquid, saliva) and retrograde (e.g., bile, gastric acid) aspirate contents. Aspiration is often the result of impaired swallowing (dysphagia), which allows oral and/or gastric contents to enter the lung, especially in individuals who also have cough dysfunction (dystussia). Cough hyposensitivity, downregulation, or desensitization- collectively referred to as - is common in individuals with dysphagia, and increases the likelihood that aspirated material will reach the lung. The consequence of hypotussia with reduced airway clearance can include respiratory tract infection, chronic inflammation, and long-term damage to the lung parenchyma. Despite the clear implications for health, the problem of managing hypotussia in individuals with dysphagia is frequently overlooked. Here, we provide an overview of the current interventions and treatment approaches for hypotussic cough. We synthesize the available literature to summarize research findings that advance our understanding of these interventions, as well as current gaps in knowledge. Further, we highlight pragmatic resources to increase awareness of hypotussic cough interventions and provide support for the clinical implementation of evidence-based treatments. In culmination, we discuss potential innovations and future directions for hypotussic cough research.
PubMed: 38933659
DOI: 10.3389/fresc.2024.1394110 -
Cureus May 2024Cystic echinococcosis, a zoonotic disease caused by the larval form of , predominantly affects the liver and lungs, with humans acting as accidental hosts.
INTRODUCTION
Cystic echinococcosis, a zoonotic disease caused by the larval form of , predominantly affects the liver and lungs, with humans acting as accidental hosts.
METHODS
Our retrospective study at the Department of Radiology and Imageology, Nizam's Institute of Medical Sciences, included 187 histopathologically or serologically proven cases. The mean age of presentation was 49.4 years.
RESULTS
Liver involvement was most prevalent, accounting for 83.4% (n=156) of cases, followed by sporadic involvement of other organs such as the mesentery, spleen, pancreas, thalamus, kidney, lung, spine, and omentum. Characteristic diagnostic features observed on imaging included peripheral calcifications in 33% of cases, internal septations in 25% (n=47), dense calcifications in 15% (n=29), daughter cysts in 6% (n=11), and floating membranes in 5% (n=10). Among hepatic lesions, 90% (n=141) were showing involvement of a single lobe. Notably, 78% (n=110) of lesions were limited to the right lobe, 21% (n=30) to the left lobe, and 1% (n=1) to the caudate lobe. The most affected hepatic segment was segment VIII, while the least common was segment I (caudate lobe). Complications were identified in 13% (n=25) of cases of hepatic hydatidosis.
CONCLUSIONS
The findings of our study emphasize the systemic nature of infection which can affect various organs in the body. It also illustrates the invaluable insights imaging provides for timely and accurate diagnosis of hydatid disease.
PubMed: 38933644
DOI: 10.7759/cureus.61180 -
Frontiers in Oncology 2024MUC21, also known as Epiglycanin, is a high-molecular-weight glycoprotein with transmembrane mucin properties. It consists of a tandem repeat domain, a stem domain, a... (Review)
Review
MUC21, also known as Epiglycanin, is a high-molecular-weight glycoprotein with transmembrane mucin properties. It consists of a tandem repeat domain, a stem domain, a transmembrane domain and a cytoplasmic tail. MUC21 is expressed is observed in normal tissues in organs like the thymus, testes, lungs, and large intestine. Research has shown that MUC21 is expressed in esophageal squamous cell carcinoma, lung adenocarcinoma, glioblastoma, thyroid cancer, melanoma, and various other malignant tumors in distinctive manner. Additionally, tumor invasion, metastasis, and poor prognosis are linked to it. Some researchers believe that MUC21 has the potential to become a new target in cancer treatment. This review aims to deliver a comprehensive overview of the glycosylation, function, and research progress of MUC21 in multiple types of cancer and infectious diseases.
PubMed: 38933439
DOI: 10.3389/fonc.2024.1410761 -
The Pan African Medical Journal 2024tuberculosis (TB) and Human Immunodeficiency Virus (HIV) remain major public health threats globally and worse when they co-exist in susceptible individuals. The study...
INTRODUCTION
tuberculosis (TB) and Human Immunodeficiency Virus (HIV) remain major public health threats globally and worse when they co-exist in susceptible individuals. The study examined TB treatment outcomes and their predictive factors among people living with HIV (PLHIVs).
METHODS
a review of TB/HIV co-infected patients who had TB treatments across comprehensive antiretroviral therapy (ART) sites with ≥500 patients was conducted in seven United States of America President's Emergency Plan for AIDS Relief (PEPFAR)-supported States in Nigeria. Data on patient background, HIV and TB care, and TB treatment outcomes were collected using an Excel abstraction template. The data was analyzed using SPSS and an association was examined using a chi-square test while binary logistic regression was used to determine predictors of TB treatment outcomes (P< 0.05).
RESULTS
two thousand six hundred and fifty-two co-infected patients participated in the study. The mean age of participants was 37 ± 14 years. A majority had TB treatment success (cured = 1059 (39.9%), completed = 1186 (44.7%)). Participants who had pulmonary TB, virally suppressed and commenced isoniazid (INH) before TB diagnosis were more likely to have a favorable TB treatment outcome compared to those who had extrapulmonary TB (AOR = 7.110, 95% CI = 1.506 - 33.565), virally unsuppressed (AOR = 1.677, 95% CI = 1.036 - 2.716) or did not commence INH before TB diagnosis (AOR = 1.486, 95% CI = 1.047 - 2.109).
CONCLUSION
site of infection, immune status, exposure to ART, and INH prophylaxis were found to predict TB treatment outcomes among PLHIVs. Stakeholders should ensure early commencement of ART and INH prophylaxis for PLHIVs.
Topics: Humans; Nigeria; HIV Infections; Adult; Female; Antitubercular Agents; Male; Tuberculosis; Middle Aged; Coinfection; Treatment Outcome; Young Adult; Anti-HIV Agents; Isoniazid; Retrospective Studies; Tuberculosis, Pulmonary
PubMed: 38933432
DOI: 10.11604/pamj.2024.47.149.35719 -
Health Science Reports Jun 2024Impaired lung function has been observed in patients following COVID-19 infection, with studies reporting persistent lung volume and diffusing capacity impairments. Some...
INTRODUCTION
Impaired lung function has been observed in patients following COVID-19 infection, with studies reporting persistent lung volume and diffusing capacity impairments. Some studies have demonstrated significantly higher small airway resistance in COVID-19 positive cases. This retrospective study aims to examine impulse oscillometry (IOS) data of patients with persistent symptoms after COVID-19 infection, focusing on the relationship between time and symptoms.
MATERIAL AND METHOD
The study analyzed data from adult patients with persistent symptoms who underwent IOS testing within and after 84 days from the diagnosis date.
RESULT
The results showed that patients within 84 days and those between 31 and 84 days had higher small airway resistance values, indicating peripheral airway disease. Patients with dyspnea exhibited higher IOS values compared to those with cough symptoms, suggesting more significant impairment in the peripheral airways.
CONCLUSION
The study highlights the importance of using comprehensive diagnostic tools like IOS to assess respiratory impairments in post-COVID-19 patients, particularly in the small airways. Understanding the relationship between time and symptoms can provide valuable insights for the treatment of peripheral airway dysfunction in post-COVID-19 patients.
PubMed: 38933420
DOI: 10.1002/hsr2.2191