Evaluating both humoral and cellular immunity is essential for optimizing vaccination strategies and preventing post-pandemic SARS-CoV-2 outbreaks. This cross-sectional study assessed cellular immunity by measuring CXCL10 mRNA expression and humoral immunity through SARS-CoV-2-specific IgG antibodies.

Whole blood samples were collected from 40 Peruvian volunteers. CXCL10 expression was evaluated in blood samples stimulated with Spike protein peptides from the Wuhan strain and Omicron BA.5 variant using RT-qPCR. Anti-spike IgG levels were measured with a semi-quantitative ELISA.

The median age was 31 years, with 62.5% females. A heterologous vaccination scheme was reported by 73%, but only 25% received their last dose within the past 6 months, and 55% completed three doses. The BNT162b2 vaccine was included in 88% of vaccination schemes, serving as the first and second dose in 48% of cases. All participants had detectable anti-spike IgG antibodies; 90% exhibited cellular responses to Wuhan peptides and 97.5% to Omicron peptides. CXCL10 mRNA expression (2^-ΔΔCT) was significantly higher for Omicron (median: 565.97; IQR: 565,148.34) compared to Wuhan (median: 18.55; IQR: 62,898.67). Higher anti-spike IgG levels correlated with age and the number of vaccine doses. Males had significantly higher CXCL10 and anti-spike IgG levels (p < 0.05). Antibody levels were greater in those recently boosted or vaccinated with mRNA-1273 (p = 0.001, p = 0.002).

Most participants exhibited robust immunity, characterized by elevated levels of CXCL10 and anti-SARS-CoV-2 IgG antibodies. These findings highlight the importance of boosters in enhancing immunity and the need for diverse techniques for measuring immunity.

Coal worker's pneumoconiosis (CWP) is an occupational disease, and the mechanisms underlying the development of its complication, nodular thyroid disease (NTD), remain unclear. This study aimed to investigate the role of miR-205-5p (miR-205-5p) in the development of nodular thyroid disease associated with coal worker's pneumoconiosis.

The potential role of pulmonary extracellular vesicles in triggering coal worker's pneumoconiosis-associated nodular thyroid disease was explored. RNA was extracted from isolated extracellular vesicle samples, and real-time fluorescent quantitative RT-qPCR was performed using specific primers and probes. The levels of miR-205-5p in the extracellular vesicles from the supernatant of each treatment group were compared, and the significant expression of miR-205-5p in the extracellular vesicles was detected by RT-qPCR to evaluate the regulatory role of lung-derived extracellular vesicles in the development of coal worker's pneumoconiosis-associated nodular thyroid disease. In addition, cell proliferation, apoptosis, and invasion capabilities were assessed using the CCK-8 assay for cell proliferation activity, Annexin V-FITC/PI double staining and flow cytometry for cell apoptosis rate, and Transwell assay for cell invasion ability.

By isolating, purifying, and analyzing extracellular vesicles from coal worker's pneumoconiosis patients and healthy controls, it was found that the expression of miR-205-5p in the plasma of coal worker's pneumoconiosis patients was significantly higher than that in the healthy controls (P<0.01). Furthermore, the expression levels of ATF4 and CHOP were also significantly increased in coal worker's pneumoconiosis patients (P<0.01), consistent with the expression trend of miR-205-5p. Further in vitro cell experiments demonstrated that miR-205-5p can promote the proliferation and formation of nodules in thyroid cells by regulating the expression of downstream target genes. This study revealed the critical role of miR-205-5p in the development of nodular thyroid disease associated with coal worker's pneumoconiosis and provided new experimental evidence for the diagnosis and treatment of this disease.

miR-205-5p in pulmonary extracellular vesicles mediates the development of nodular thyroid disease associated with coal worker's pneumoconiosis through the ATF4/CHOP signaling axis. Further research is essential to comprehensively investigate the specific targets through which miR-205-5p derived from pulmonary extracellular vesicles triggers the development of nodular thyroid disease associated with coal worker's pneumoconiosis via the ATF4/CHOP signaling axis.

In this article, we report the case of a 58-year-old man who was admitted to our institution with acute dyspnea and poor hemodynamic condition. He had undergone double mitral-aortic valve replacement five years earlier for rheumatic heart disease. Transthoracic echocardiography (TTE), cinefluoroscopy, and transesophageal echocardiography (TEE) revealed a significant reduction in the opening of the mechanical mitral valve leaflets. An urgent redo surgery was performed, during which the pannus was removed, ensuring the restoration of normal leaflet motion. This clinical case presents two rare circumstances: first, the unusual diaphragmatic pannus completely masking the mechanical mitral prosthetic valve, and second, the development of pannus at the level of the mitral mechanical prosthesis rather than the aortic mechanical prosthesis.

Previous studies have shown that asthma is associated with a less traditional diet pattern with an unbalanced polyunsaturated fatty acids (PUFAs) distribution. This study aimed to investigate the association between asthma and PUFA intake in Brazilian adolescents.

This is a cross-sectional study, using data from the Study of Cardiovascular Risks in Adolescents-ERICA, a national, school-based multicenter survey with a sample representative of Brazilian adolescents (12-17 years old). The presence of at least one wheezing attack in the last 12 months defined asthma. The intake of the following PUFAs was evaluated: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LA) and arachidonic acid (ARA) as well as N6N3 ratio (the sum of LA and ARA over ALA, DHA and EPA). The odds ratio (OR) and the respective 95% Confidence Interval (95% CI) between asthma and PUFAs intake, as well as other study variables was calculated using Logistic Regression.

A total of 64,904 participants were included for the analysis. After adjustment, asthma remained significantly associated with ALA (OR:1.05; CI95%:1.02-1.09) and EPA (OR:0.61; 95%CI:0.39-0.95), being the first a positive association and the latter a negative one. There were no significant association between asthma and N6N3 ratio, as well as the other PUFAs evaluated.

Our findings reveal a higher chance of asthma among Brazilian adolescents with increased ALA consumption and, elevated intake of EPA was associated with decreased odds.

Heart failure (HF) and pulmonary hypertension (PH) are prevalent cardiovascular diseases that often coexist and share common pathophysiological mechanisms, particularly dysregulation of nitric oxide metabolism, yet their clinical efficacy has been inconsistent.

We systematically searched databases including PubMed, Web of Science, Embase, and the Cochrane Library for studies published over the past 15 years assessing nitrate/nitrite effects on cardiac function, hemodynamics, and exercise capacity in HF or PH patients. Data were analyzed using a random-effects model, with results as mean differences (MD) and 95% confidence intervals (CI). PROSPERO registration: CRD42024614911.

14 trials (n = 469) involving HF, PH, or pulmonary hypertension due to left heart disease (PH-LHD) were included. During exercise, nitrates significantly improved cardiac function in HF/PH-LHD patients, increasing stroke volume by 0.86 mL (95% CI 0.35 to 1.36; P < 0.05) and cardiac output by 0.57 L/min (95% CI 0.12 to 1.02; P < 0.05). At rest, nitrates reduced hemodynamic parameters in HF/PH patients: systolic blood pressure  ,SBP (- 0.36 mmHg; 95% CI - 0.53 to - 0.18; P < 0.05), diastolic blood pressure, DBP (- 0.19 mmHg; 95% CI - 0.37 to - 0.01; P < 0.05), and right atrial pressure, RAP (- 0.70 mmHg; 95% CI - 1.35 to - 0.05; P < 0.05). These effects were attenuated during exercise. Neither administration methods, exercise intensity, nor ejection fraction significantly influenced hemodynamic improvements. Nitrates did not significantly improve oxygen consumption at rest (- 0.17 mL/min; 95% CI - 0.56 to 0.21; P = 0.65) or during exercise (0.25 mL/kg/min; 95% CI - 0.04 to 0.54; P = 0.10).

Nitrate/nitrite therapy improves cardiopulmonary hemodynamics at rest and enhances cardiac function during exercise in HF and PH patients, though the drug-related benefits appear more limited. These hemodynamic improvements occur consistently regardless of exercise intensity or baseline ejection fraction. The dissociation between hemodynamic and functional measures suggests nitrate medications may be particularly valuable for addressing resting hemodynamic overload in this population.

Ventilator-associated pneumonia (VAP) after tracheal intubation is a major infectious complication in patients in the intensive care unit (ICU), with an incidence of 8-28%. Oral care in the ICU is essential; however, the presence of an intubation tube and restricted mouth opening cause complications. A healthy commensal microflora in the oral cavity resists colonization by respiratory pathogens, and poor oral hygiene may increase the risk for VAP. In this study, we examined the effectiveness of oral care on oral bacterial counts and microbial diversity in patients admitted to the ICU.

Fifteen ICU patients were included in this study. Oral microbiome samples were collected by swabbing the surface of the tongue. Oral bacterial counts were measured at four time points: before and after oral care, both pre- and post-extubation. Additionally, microbiome analysis was conducted twice: once before oral care pre-extubation, and once before oral care post-extubation. Oral bacterial counts were assessed using a bacterial counter, and microbiome analysis was performed through 16S rRNA gene amplicon sequencing.

Oral bacterial counts significantly decreased after oral care at both pre- and post-extubation time points. Microbiome analysis revealed significant differences in alpha diversity pre- and post-extubation samples. Samples post extubation were less diverse.

This study demonstrates that oral care effectively reduces bacterial counts in ICU patients, both pre- and post-extubation. Microbiome analysis revealed shifts in microbial diversity, suggesting that the oral microbiota was disrupted during intubation. Given the risk of VAP, oral care may play an important role to prevent VAP in ICU settings.

Multidrug-resistant Klebsiella pneumoniae (MDR-KP) poses a significant global health threat, associated with high morbidity and mortality rates among hospitalized patients. The interaction between MDR-KP and its host is highly complex, and few studies have investigated these interactions from both the pathogen and host perspectives. Here, we explored these interactions in a mouse model of pneumonia using dual RNA-seq analysis.

PCR identification and antimicrobial susceptibility test were employed to screen for MDR-KP strains. A mouse model of pneumonia was established through aerosolized intratracheal inoculation with high-dose or low-dose bacteria. Bacterial loads, pathological changes, inflammatory cytokine expression, and immune cell infiltration were assessed post-challenge. Dual RNA-seq analysis was conducted on lung tissues following infection.

NY13307 was identified as an MDR-KP strain with minimal virulence factor genes and broad-spectrum drug resistance. High-dose bacteria induced more severe pulmonary pathological changes, a significant increase in bacterial load, and notably elevated secretion of inflammatory cytokines compared to low-dose bacteria. Alveolar macrophages and resident interstitial macrophages were identified as the primary sources of these cytokines. Further RNA-seq analysis revealed that, compared to the low-dose group, the high-dose group significantly upregulated hypoxia and pro-inflammatory cytokine-related genes in the host, and siderophore-related genes in the bacteria. Correlation analysis demonstrated a significant association between siderophore-related genes and clusters of genes related to pro-inflammatory cytokines and hypoxia.

In this mouse model of bacterial pneumonia, excessive siderophore expression may trigger the activation of hypoxia signaling pathways and the release of pro-inflammatory cytokines, ultimately reducing survival rates.

Scedosporium boydii infections pose diagnostic challenges due to their nonspecific clinical manifestations and slow growth characteristics in conventional cultures. This paper highlights the diagnostic value of molecular technology combined with targeted prolonged culture for rare fungi. Unitl now, only one case was identified using metagenomic next-generation sequencing (mNGS). This case represents the first report of a 20-day delayed culture confirmation of S. boydii guided by mNGS results in a non-immunocompromised chronic obstructive -with history of COPD who was admitted with fever and cough. Despite two weeks of antibacterial treatment, chest computed tomography (CT) showed worsening infection. To clarify the pathogen, mNGS and bacterial culture of bronchoalveolar lavage fluid (BALF) were performed. Subsequent culture and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) confirmed the growth of Scedosporium species. Based on clinical presentation, chest CT findings, mNGS results, pulmonary Scedosporiosis was diagnosed, and an antifungal treatment regimen (200 mg BID orally) was initiated. Subsequent culture confirmed S. boydii growth and antifungal susceptibility results were also obtained. After six weeks of voriconazole treatment, he was discharged from the hospital and continued to take oral medication for three months. He was fully recovered without recurrence after six months of follow-up. The present case suggests that mNGS findings can unveil cryptic pathogens like Scedosporium. Use mNGS results to trigger intentional, extended targeted cultivation- challenging standard incubation times- especially in non-immunocompromised hosts with underlying lung disease. Seamless clinician-laboratory collaboration is paramount for treatment success.

Eosinophils have been implicated as key effectors in the emergence of chronic cough. But causality has not been firmly established, and many patients with cough secondary to eosinophilic bronchitis (EB) are likely misdiagnosed as asthmatics based on successful empiric trials using inhaled corticosteroids. Better diagnostics and more precise therapeutic strategies for EB and other diseases that lead to chronic cough remain important but unmet clinical needs.

With the goal of better defining the mechanisms of cough in disease, we established a model of EB in guinea pigs using allergen challenges that induce a cough hypersensitivity responsive to steroid therapy.

The heightened cough responsiveness associated with the eosinophilic inflammation was mimicked by LTD₄ inhalation and prevented by cysLT₁ receptor blockade with pranlukast or montelukast. But cysLT₁ receptor antagonism failed to prevent the eosinophilic infiltration of the airways evoked by allergen challenge. Additionally, inhalation of the mast cell selective stimulant Compound 48/80 mimicked the effects of allergen challenge on cough but failed to significantly increase eosinophilic infiltration of the airways. We also observed that thromboxane A2, through TP receptor engagement, acts downstream from and simultaneously with the leukotrienes to promote cough hypersensitivity in EB.

These results suggest that mast cells and not eosinophils may be essential to the emergence of cough hypersensitivity in EB. We speculate that therapeutic strategies targeting mast cells, cysLT₁ receptors, and TP receptors may represent endotype-specific treatments for chronic cough.

Acute respiratory infections (ARI) are a major cause of morbidity and lost workdays in both military and non-military populations. To better understand these infections and their outcomes, the Infectious Diseases Clinical Research Program has enabled nine major ARI clinical research protocols in the last decade, including observational studies and trials, spanning emerging and reemerging ARI threats including Severe Acute Respiratory Syndrome Coronavirus 2, influenza, adenovirus, entero/rhinovirus, human metapneumovirus, respiratory syncytial virus, and other pathogens. These protocols have resulted in epidemiological, clinical and laboratory data and biospecimens from over 26,000 participants, most of whom were beneficiaries of a geographically distributed Military Health System.

The Acute Respiratory Infection Repository Protocol establishes a unique Department of Defense (DoD) research resource through the pooling of data and specimens from nine ARI protocols into a master, standardized database with a linked specimen repository. This will enable further targeted scientific questions in participant-level pooled meta-analyses and will serve as an on-demand repository for rapid assay development, sample size estimations for prospective studies, and observational study/clinical trial design (including as part of future rapid pandemic research response). Accordingly, the objectives and study design of this protocol are broad. This protocol will allow analyses on outcomes including: (i) short-term ARI outcomes such as hospitalization, work days lost, symptom severity and duration; (ii) post-acute ARI outcomes, including persistence of symptoms, return-to-health, post-ARI medical encounters; (iii) vaccine effectiveness for Coronavirus disease 2019 (COVID-19), influenza, and adenovirus vaccines; (iv) ARI infection and vaccination elicited immune responses (humoral, T-cell, other); (v) therapeutic effectiveness of COVID-19 and influenza antivirals (acute symptoms, hospitalization, post-acute sequelae); (vi) effectiveness of non-pharmaceutical interventions (e.g., masking) against infection; (vii) prognostic and mechanistic host viral biomarkers which correlate with the above outcomes; (viii) ARI diagnostic assay validity and performance. This repository protocol is inherently broad in scope; the collation of standardized data and phenotype-linked specimens is a fundamental, primary objective.

This protocol will support statistical and laboratory analyses, including activities related to rapid epidemic response such as assay development and rapid sample size calculations for clinical trials. A series of more specific scientific questions from current and future collaborators will leverage this joint database and specimen repository; these questions will target important aspects of ARI infection, transmission, outcomes, and treatment. Future protocols (and ongoing data from existing IDCRP protocols) will be added to this collaborative repository protocol.