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Particle and Fibre Toxicology May 2024Rural regions of the western United States have experienced a noticeable surge in both the frequency and severity of acute wildfire events, which brings significant...
BACKGROUND
Rural regions of the western United States have experienced a noticeable surge in both the frequency and severity of acute wildfire events, which brings significant challenges to both public safety and environmental conservation efforts, with impacts felt globally. Identifying factors contributing to immune dysfunction, including endocrinological phenotypes, is essential to understanding how hormones may influence toxicological susceptibility.
METHODS
This exploratory study utilized male and female C57BL/6 mice as in vivo models to investigate distinct responses to acute woodsmoke (WS) exposure with a focus on sex-based differences. In a second set of investigations, two groups were established within the female mouse cohort. In one group, mice experienced ovariectomy (OVX) to simulate an ovarian hormone-deficient state similar to surgical menopause, while the other group received Sham surgery as controls, to investigate the mechanistic role of ovarian hormone presence in driving immune dysregulation following acute WS exposure. Each experimental cohort followed a consecutive 2-day protocol with daily 4-h exposure intervals under two conditions: control HEPA-filtered air (FA) and acute WS to simulate an acute wildfire episode.
RESULTS
Metals analysis of WS particulate matter (PM) revealed significantly increased levels of Cu, W, Pb, and U, compared to filtered air (FA) controls, providing insights into the specific metal components most impacted by the changing dynamics of wildfire occurrences in the region. Male and female mice exhibited diverse patterns in lung mRNA cytokine expression following WS exposure, with males showing downregulation and females displaying upregulation, notably for IL-1β, TNF-α, CXCL-1, CCL-5, TGF-β, and IL-6. After acute WS exposure, there were notable differences in the responses of macrophages, neutrophils, and bronchoalveolar lavage (BAL) cytokines IL-10, IL-6, IL-1β, and TNF-α. Significant diverse alterations were observed in BAL cytokines, specifically IL-1β, IL-10, IL-6, and TNF-α, as well as in the populations of immune cells, such as macrophages and polymorphonuclear leukocytes, in both Sham and OVX mice, following acute WS exposure. These findings elucidated the profound influence of hormonal changes on inflammatory outcomes, delineating substantial sex-related differences in immune activation and revealing altered immune responses in OVX mice due to ovarian hormone deficiency. In addition, the flow cytometry analysis highlighted the complex interaction between OVX surgery, acute WS exposure, and their collective impact on immune cell populations within the hematopoietic bone marrow niche.
CONCLUSIONS
In summary, both male and female mice, alongside females subjected to OVX and those who had sham surgery, exhibit significant variations in the expression of proinflammatory cytokines, chemokines, lung mRNA gene expression, and related functional networks linked to signaling pathways. These differences potentially act as mediators of sex-specific and hormonal influences in the systemic inflammatory response to acute WS exposure during a wildfire event. Understanding the regulatory roles of genes expressed differentially under environmental stressors holds considerable implications, aiding in identifying sex-specific therapeutic targets for addressing acute lung inflammation and injury.
Topics: Animals; Female; Male; Mice, Inbred C57BL; Inhalation Exposure; Wildfires; Particulate Matter; Sex Factors; Cytokines; Lung; Smoke; Air Pollutants; Bronchoalveolar Lavage Fluid; Ovariectomy; Mice; Ovary
PubMed: 38797836
DOI: 10.1186/s12989-024-00587-5 -
International Journal of Molecular... May 2024Lefamulin is a first-in-class systemic pleuromutilin antimicrobial and potent inhibitor of bacterial translation, and the most recent novel antimicrobial approved for...
Lefamulin is a first-in-class systemic pleuromutilin antimicrobial and potent inhibitor of bacterial translation, and the most recent novel antimicrobial approved for the treatment of community-acquired pneumonia (CAP). It exhibits potent antibacterial activity against the most prevalent bacterial pathogens that cause typical and atypical pneumonia and other infectious diseases. Early studies indicate additional anti-inflammatory activity. In this study, we further investigated the immune-modulatory activity of lefamulin in the influenza A/H1N1 acute respiratory distress syndrome (ARDS) model in BALB/c mice. Comparators included azithromycin, an anti-inflammatory antimicrobial, and the antiviral oseltamivir. Lefamulin significantly decreased the total immune cell infiltration, specifically the neutrophils, inflammatory monocytes, CD4 and CD8 T-cells, NK cells, and B-cells into the lung by Day 6 at both doses tested compared to the untreated vehicle control group (placebo), whereas azithromycin and oseltamivir did not significantly affect the total immune cell counts at the tested dosing regimens. Bronchioalveolar lavage fluid concentrations of pro-inflammatory cytokines and chemokines including TNF-α, IL-6, IL-12p70, IL-17A, IFN-γ, and GM-CSF were significantly reduced, and MCP-1 concentrations were lowered (not significantly) by lefamulin at the clinically relevant 'low' dose on Day 3 when the viral load peaked. Similar effects were also observed for oseltamivir and azithromycin. Lefamulin also decreased the viral load (TCID) by half a log10 by Day 6 and showed positive effects on the gross lung pathology and survival. Oseltamivir and lefamulin were efficacious in the suppression of the development of influenza-induced bronchi-interstitial pneumonia, whereas azithromycin did not show reduced pathology at the tested treatment regimen. The observed anti-inflammatory and immune-modulatory activity of lefamulin at the tested treatment regimens highlights a promising secondary pharmacological property of lefamulin. While these results require confirmation in a clinical trial, they indicate that lefamulin may provide an immune-modulatory activity beyond its proven potent antibacterial activity. This additional activity may benefit CAP patients and potentially prevent acute lung injury (ALI) and ARDS.
Topics: Animals; Influenza A Virus, H1N1 Subtype; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections; Disease Models, Animal; Diterpenes; Cytokines; Azithromycin; Oseltamivir; Female; Lung; Antiviral Agents; Tetrahydronaphthalenes; Respiratory Distress Syndrome; Immunomodulating Agents; Bronchoalveolar Lavage Fluid; Polycyclic Compounds; Thioglycolates
PubMed: 38791439
DOI: 10.3390/ijms25105401 -
Biomedicines May 2024Post-irradiation xerostomia remains a significant quality of life concern for patients with head and neck cancers. Conventional therapies offer limited effectiveness....
Post-irradiation xerostomia remains a significant quality of life concern for patients with head and neck cancers. Conventional therapies offer limited effectiveness. This study aims to investigate the therapeutic potential of office-based salivary ductal steroid irrigation in patients with post-irradiation xerostomia. This single-center observational study recruited 147 head and neck cancer patients suffering from post-irradiation xerostomia between November 2020 and October 2022. All included subjects received at least one round of successful salivary ductal cannulation and irrigation. The primary measure of efficacy was improvement in subjective xerostomia and objective salivary amylase levels. A logistic regression was employed to evaluate factors affecting treatment responsiveness. The response rate among nasopharyngeal cancer (NPC) patients was 74.8%, and that among non-NPC cancer was 65.6%, without significant intergroup differences. The statistical analysis revealed no significant influence of age, gender, or disease stage on treatment responsiveness. Post-treatment salivary amylase levels were significantly higher in responsive non-NPC patients. In conclusion, salivary ductal steroid irrigation emerged as a promising therapeutic modality for the management of post-irradiation xerostomia in head and neck cancer patients. While no explicit factors were predictive of responsiveness, the high rate of symptom improvement suggests that this therapy may be a viable alternative for patients that are refractory to standard treatments.
PubMed: 38790995
DOI: 10.3390/biomedicines12051033 -
Hand Surgery & Rehabilitation Jun 2024A 41-year-old male presented with an insidious onset of pain and swelling about the dorsal wrist, and was found to have a Brodie's abscess in the distal radius. The...
CASE
A 41-year-old male presented with an insidious onset of pain and swelling about the dorsal wrist, and was found to have a Brodie's abscess in the distal radius. The patient had a history of a distal radius fracture, treated with external fixation, nineteen years prior, which we believe contributed to the infection. The patient was treated surgically with abscess irrigation, debridement, bony curettage, bioactive glass S53P4 allograft, with concurrent antibiotic therapy.
CONCLUSION
Brodie's abscesses can have atypical presentations, and a thorough history must be obtained from patients to identify any potential sources of infection.
Topics: Humans; Male; Adult; Radius Fractures; Abscess; Debridement; Fracture Fixation; External Fixators; Anti-Bacterial Agents; Osteomyelitis
PubMed: 38788799
DOI: 10.1016/j.hansur.2024.101722 -
Antibiotics (Basel, Switzerland) May 2024Periprosthetic shoulder infection (PSI) remains a challenging complication after shoulder arthroplasty. Therapeutic options include one- or two-stage revision,... (Review)
Review
Periprosthetic shoulder infection (PSI) remains a challenging complication after shoulder arthroplasty. Therapeutic options include one- or two-stage revision, irrigation and debridement, and resection arthroplasty. With our systematic review and meta-analysis, we aimed to compare one- and two-stage revisions for periprosthetic shoulder joint infections and determine the most appropriate therapeutic procedure. We performed an extensive literature search in PubMed, Ovid Medline, Cochrane Library, Web of Science, and CINAHL and filtered out all relevant studies. The meta-analysis was performed using the random-effects model, heterogeneity was analyzed using I, and publication bias was assessed using the Egger's test. A total of 8 studies with one-stage revisions, 36 studies with two-stage revisions, and 12 studies with both one-stage and two-stage revisions were included. According to the random-effects model, the reinfection rate for the entirety of the studies was 12.3% (95% Cl: 9.6-15.3), with a low-to-moderate heterogeneity of I = 47.72%. The reinfection rate of the one-stage revisions was 10.9%, which was significantly lower than the reinfection rate of the two-stage revisions, which was 12.93% ( = 0.0062). The one-stage revision rate was significantly lower with 1.16 vs. 2.25 revisions in the two-stage revision group ( < 0.0001). The postoperative functional outcome in one-stage-revised patients was comparable but not statistically significant ( = 0.1523). In one- and two-stage revisions, most infections were caused by . In summary, our systematic review and meta-analysis show the superiority of single-stage revision regarding reinfection and revision rates in periprosthetic shoulder joint infection.
PubMed: 38786168
DOI: 10.3390/antibiotics13050440 -
Zhonghua Yi Xue Za Zhi May 2024To investigate the effects of the epidermal growth factor receptor(EGFR) inhibitor Gefitinib on airway inflammation and airway remodelling in asthmatic C57BL/6 mice,...
To investigate the effects of the epidermal growth factor receptor(EGFR) inhibitor Gefitinib on airway inflammation and airway remodelling in asthmatic C57BL/6 mice, and to analyze its possible mechanisms. Male C57BL/6 mice, aged 6-8 weeks, were randomly assigned into five groups: Group A (control group), Group B (asthma group), Group C (asthma+20 mg/kg gefitinib group), Group D (asthma+40 mg/kg gefitinib group), and Group E (40 mg/kg gefitinib group), with seven mice per group. Mice were sensitized by intraperitoneal injection of a mixture of 0.2 ml solution containing OVA and Al(OH) [20 μg OVA+2 mg Al(OH) dissolved in 0.2 ml of physiological saline] at Day 0 and 14. Starting from Day 25 to 31, Group B, C, and D were challenged with nebulization of 1% OVA solution (8 ml) to induce asthma, once a day for approximately 40 minutes, with continuous aerosolization for 7 days. Group C and D were given 0.2 ml of Gefitinib dissolved in 0.5% carboxymethylcellulose sodium (CMCNa) by gavage half an hour before challenging, and Group E was simultaneously given with 0.2 ml of Gefitinib dissolved in 0.5% CMCNa only. Group A and B were given an equivalent volume of 0.5% CMCNa by gavage. After 24 h of final challenge, the bronchoalveolar lavage fluid (BALF) was prepared for the determination of total cell count and eosinophil count. The levels of total immune globulin E (IgE) in serum and interleukin (IL)-4, IL-5 and IL-13 in BALF and lung tissue homogenates were measured by ELISA. The mRNA expression levels of IL-4, IL-5, IL-13 in lung were measured. Immunohistochemistry and Western blot experiments were used to detect the expression levels of EGFR in lung tissues. In Group B, the level of total IgE in serum, total cell count, eosinophil count, the levels of IL-4, IL-5, IL-13 in BALF and the phosphorylation of EGFR and its downstream activation in lung were higher than those in Group A (all <0.05). The levels of total IgE in serum [(261.32±44.38) ng/ml, (194.09±52.39) ng/ml vs (1 023.70±105.51) ng/ml], total cell count [(23.70±4.08)×10/ml, (14.92±4.06)×10/ml vs (35.36±6.30)×10/ml], eosinophil count [(108.00±13.69)×10/ml, (67.00±17.28)×10/ml vs (147.86±20.06)×10/ml], IL-4 [(36.42±4.48) pg/ml, (30.45±8.12) pg/ml vs (58.72±7.17) pg/ml], IL-5 [(16.20±4.62) pg/ml, (13.38±5.14) pg/ml vs (23.46±5.38) pg/ml], IL-13 [(18.45±7.28) pg/ml, (14.33±7.70) pg/ml vs (104.12±24.66) pg/ml] in BALF of Group C and D were lower than those in Group B (all <0.05). The levels of IL-4, IL-5, and IL-13 as well as their mRNA levels in the lung tissue of Group C and D were lower than those in Group B (all <0.05). In Group C and D, the positive expression rate of phosphorylated epidermal growth factor receptor (p-EGFR) in lung tissue [(40.53±6.80)%, (23.60±4.42)% vs (70.78±5.36)%], p-EGFR/EGFR (61.68±7.48, 51.13±5.19 vs 105.90±11.66), phosphorylated extracellular regulated protein kinase (p-Erk)/extracellular regulated protein kinase (Erk) (75.28±7.11, 47.54±4.83 vs 98.76±4.71), and phosphorylated protein kinase B (p-Akt)/protein kinase B (Akt) (96.24±5.40, 68.52±2.73 vs 103.30±4.52) was lower than those of Group B (all <0.05). There was no statistically significant difference in the relevant indicators between Group A and E (all >0.05). Gefitinib may alleviate airway inflammation and airway remodeling in asthmatic mice by inhibiting EGFR phosphorylation and affecting the activation of downstream Erk and Akt.
Topics: Animals; Asthma; Mice; Mice, Inbred C57BL; Gefitinib; Airway Remodeling; Male; Bronchoalveolar Lavage Fluid; Inflammation; Interleukin-4; Quinazolines; ErbB Receptors; Ovalbumin; Lung; Interleukin-5; Interleukin-13; Eosinophils; Disease Models, Animal
PubMed: 38782755
DOI: 10.3760/cma.j.cn112137-20231205-01297 -
Compendium of Continuing Education in... Mar 2024The objective of this in vitro study was to compare the area of oral biofilm removal by the Philips Sonicare Quad Stream (PSQS) nozzle (used on a Philips® Sonicare®... (Comparative Study)
Comparative Study
The objective of this in vitro study was to compare the area of oral biofilm removal by the Philips Sonicare Quad Stream (PSQS) nozzle (used on a Philips® Sonicare® Power Flosser) and a traditional oral irrigator with a standard nozzle (TOIS) when used per the directions for use (DFU) instructions for both devices.
Topics: Biofilms; Humans; Therapeutic Irrigation; In Vitro Techniques; Equipment Design
PubMed: 38781414
DOI: No ID Found -
Compendium of Continuing Education in... Mar 2024Interdental cleaning is critical to maintaining oral health, preventing dental issues, and promoting overall well-being. However, many patients either struggle with...
Interdental cleaning is critical to maintaining oral health, preventing dental issues, and promoting overall well-being. However, many patients either struggle with consistently following recommended interdental care routines or have poor technique when complying with recommendations. Addressing this problem requires a multifaceted approach comprised of tailored patient education and patient-clinician partnership to provide both an effective interdental cleaning tool and an accessible method for the patient to implement the modified interdental habit into their routine. The aim of this article is to discuss the different modalities for interdental cleaning, how to assess patient candidacy for different interdental cleaning modalities, and behavior-change strategies to promote patient compliance to recommended interdental care.
Topics: Humans; Patient Compliance; Oral Hygiene; Patient Education as Topic; Therapeutic Irrigation; Dental Devices, Home Care; Health Behavior
PubMed: 38781409
DOI: No ID Found -
MSphere Jun 2024Clinical metaproteomics has the potential to offer insights into the host-microbiome interactions underlying diseases. However, the field faces challenges in...
UNLABELLED
Clinical metaproteomics has the potential to offer insights into the host-microbiome interactions underlying diseases. However, the field faces challenges in characterizing microbial proteins found in clinical samples, usually present at low abundance relative to the host proteins. As a solution, we have developed an integrated workflow coupling mass spectrometry-based analysis with customized bioinformatic identification, quantification, and prioritization of microbial proteins, enabling targeted assay development to investigate host-microbe dynamics in disease. The bioinformatics tools are implemented in the Galaxy ecosystem, offering the development and dissemination of complex bioinformatic workflows. The modular workflow integrates MetaNovo (to generate a reduced protein database), SearchGUI/PeptideShaker and MaxQuant [to generate peptide-spectral matches (PSMs) and quantification], PepQuery2 (to verify the quality of PSMs), Unipept (for taxonomic and functional annotation), and MSstatsTMT (for statistical analysis). We have utilized this workflow in diverse clinical samples, from the characterization of nasopharyngeal swab samples to bronchoalveolar lavage fluid. Here, we demonstrate its effectiveness via analysis of residual fluid from cervical swabs. The complete workflow, including training data and documentation, is available via the Galaxy Training Network, empowering non-expert researchers to utilize these powerful tools in their clinical studies.
IMPORTANCE
Clinical metaproteomics has immense potential to offer functional insights into the microbiome and its contributions to human disease. However, there are numerous challenges in the metaproteomic analysis of clinical samples, including handling of very large protein sequence databases for sensitive and accurate peptide and protein identification from mass spectrometry data, as well as taxonomic and functional annotation of quantified peptides and proteins to enable interpretation of results. To address these challenges, we have developed a novel clinical metaproteomics workflow that provides customized bioinformatic identification, verification, quantification, and taxonomic and functional annotation. This bioinformatic workflow is implemented in the Galaxy ecosystem and has been used to characterize diverse clinical sample types, such as nasopharyngeal swabs and bronchoalveolar lavage fluid. Here, we demonstrate its effectiveness and availability for use by the research community via analysis of residual fluid from cervical swabs.
Topics: Proteomics; Humans; Workflow; Computational Biology; Host Microbial Interactions; Mass Spectrometry; Microbiota; Bronchoalveolar Lavage Fluid; Bacterial Proteins
PubMed: 38780289
DOI: 10.1128/msphere.00793-23 -
Zhongguo Gu Shang = China Journal of... May 2024To explore the clinical efficacy of antibiotic bone cement covered reconstruction steel plate in the treatment of infected anterior pelvic ring fracture.
OBJECTIVE
To explore the clinical efficacy of antibiotic bone cement covered reconstruction steel plate in the treatment of infected anterior pelvic ring fracture.
METHODS
From January 2017 to March 2022, 11 patients with infected anterior pelvic ring fracture were treated with antibiotic bone cement covered reconstruction steel plate including 7 males and 4 females and the age ranged from 27 to 49 years old. The pelvic fractures were classified according to the Tile typology: 4 cases of C1 type, 4 cases of C2 type, and 3 cases of C3 type. Among them, 2 cases of infected anterior ring were infected after internal fixation of anterior ring, and 9 patients were infected with infected anterior ring due to incomplete early debridement, which was classified as infected according to the injury severity score(ISS) for 24 to 38 scores. The anterior ring was internally fixed by extended debridement, irrigation, and antibiotic bone cement covered reconstruction plate, and the posterior ring fractures were all closed reduction and internally fixed with sacroiliac screws.
RESULTS
All 11 cases obtained follow-up from 13 to 20 months. Among them, 2 patients had recurrence of postoperative infection, 1 case was re-dissected and replaced with antibiotic bone cement-coated internal fixation, and 1 case had a milder infection without accumulation of the medullary cavity, and the infection was controlled by retaining the plate and replacing the antibiotic bone cement only after dissecting. Two cases developed incisional oozing, which healed after removal of the internal fixation three months postoperatively. All patients did not show pelvic fracture redisplacement or reinfection during the follow-up period. All 11 cases eventually healed bony. At the final follow-up, according to the Matta score, the fracture reduction was excellent in 6 cases, good in 4, and possible in 1. According to the Majeed functional score, it was excellent in 6, good in 3, and possible in 2.
CONCLUSION
Antibiotic bone cement covered reconstruction plate is effective in the treatment of infected anterior pelvic ring fracture, with high intraoperative safety and low recurrence rate of infection, which is conducive to the early postoperative rehabilitation and significantly shortens the course of the disease.
Topics: Humans; Male; Female; Adult; Middle Aged; Bone Cements; Pelvic Bones; Bone Plates; Fractures, Bone; Anti-Bacterial Agents; Fracture Fixation, Internal; Plastic Surgery Procedures
PubMed: 38778527
DOI: 10.12200/j.issn.1003-0034.20230926