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PloS One 2024Despite integrated prevention and control measures, the prevalence of hookworm is still high in Ethiopia. The re-infection rates and predictors are poorly addressed....
BACKGROUND
Despite integrated prevention and control measures, the prevalence of hookworm is still high in Ethiopia. The re-infection rates and predictors are poorly addressed. Therefore, this study aimed to determine the patterns of hookworm re-infection rates and predictors among schoolchildren in northwest Ethiopia.
METHODS
A prospective follow-up study was conducted among 86 schoolchildren from May to December 2022. Data on predictors was collected using a questionnaire. Stool samples were collected and processed via Kato-Katz, McMaster, and spontaneous tube sedimentation techniques. All hookworm-infected children were treated with albendazole and followed for six months. The re-infection rates of hookworm were checked in the 4th and 6th months. Data was entered into Epi-data version 3.1 and analysed using SPSS version 25. Descriptive statistics were used to compute the re-infection rate. The associations of predictors with hookworm re-infection rates were calculated by logistic regression. Variables with a p-value < 0.05 were considered statistically significant.
RESULTS
Of the 86, 81 schoolchildren completed the study. The prevalence of hookworm re-infection in the 4th and 6th months was 23.5% and 33.3%, respectively. Living with family members greater than five (p = .017), poor utilization of latrine (p = .008), infrequent shoe wear (p = .039), and participating in irrigation (p = .020) were the predictors significantly associated with hookworm re-infections.
CONCLUSIONS
The re-infection rate was high during the fourth and sixth months. Participating in irrigation, infrequent shoe wear, and poor latrine utilization were predictors of hookworm re-infection. Therefore, mass drug administration, regular shoe wearing, and health education should be advocated.
Topics: Humans; Ethiopia; Child; Male; Female; Hookworm Infections; Prospective Studies; Albendazole; Prevalence; Reinfection; Adolescent; Feces; Follow-Up Studies; Anthelmintics; Ancylostomatoidea; Schools; Animals
PubMed: 38805475
DOI: 10.1371/journal.pone.0303502 -
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 -
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 -
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 -
Brazilian Dental Journal 2024This study assessed the intratubular antibacterial ability of different activated irrigations after chemical mechanical preparation. Seventy-two palatal root canals of...
This study assessed the intratubular antibacterial ability of different activated irrigations after chemical mechanical preparation. Seventy-two palatal root canals of upper molars were infected with Enterococcus faecalis for 4 weeks, and then initial bacterial collection from the main root canal was performed. The root canals were prepared by using a WaveOne Gold large (45/.05) and distributed into 6 groups according to the activation of the final irrigation: ultrasonic activation (UA), XP-Endo Finisher (25/.00), XP Clean (25/.02), EasyClean (25/.04) in reciprocating motion and continuous rotary motion (ECRot), and conventional irrigation. After final irrigation, another bacterial collection from the main root canal was performed, and the root was sectioned transversely in three-thirds and stained for analysis by confocal laser microscopy. Intratubular bacteria were collected through dentin powder and plated for bacterial viability analysis. Intergroup and intragroup comparisons were performed by using analysis of variance and repeated measures analysis of variance, respectively, both at 5% significance. ECRot had higher antibacterial ability than UA (p<0.05), and both were superior to the other groups (p<0.05) in both methodologies. It can be concluded that activation of final irrigation enhances the disinfection of the root canal system, and activators have different efficacies.
Topics: Humans; Root Canal Irrigants; Root Canal Preparation; Enterococcus faecalis; Anti-Bacterial Agents; Dental Pulp Cavity; Microscopy, Confocal; Therapeutic Irrigation; Molar
PubMed: 38775594
DOI: 10.1590/0103-6440202405883 -
Frontiers in Cellular and Infection... 2024Traditional microbiological detection methods used to detect pulmonary infections in people living with HIV (PLHIV) are usually time-consuming and have low sensitivity,...
BACKGROUND
Traditional microbiological detection methods used to detect pulmonary infections in people living with HIV (PLHIV) are usually time-consuming and have low sensitivity, leading to delayed treatment. We aimed to evaluate the diagnostic value of metagenomics next-generation sequencing (mNGS) for microbial diagnosis of suspected pulmonary infections in PLHIV.
METHODS
We retrospectively analyzed PLHIV who were hospitalized due to suspected pulmonary infections at the sixth people hospital of Zhengzhou from November 1, 2021 to June 30, 2022. Bronchoalveolar lavage fluid (BALF) samples of PLHIV were collected and subjected to routine microbiological examination and mNGS detection. The diagnostic performance of the two methods was compared to evaluate the diagnostic value of mNGS for unknown pathogens.
RESULTS
This study included a total of 36 PLHIV with suspected pulmonary infections, of which 31 were male. The reporting period of mNGS is significantly shorter than that of CMTs. The mNGS positive rate of BALF samples in PLHIV was 83.33%, which was significantly higher than that of smear and culture (44.4%, P<0.001). In addition, 11 patients showed consistent results between the two methods. Futhermore, mNGS showed excellent performance in identifying multi-infections in PLHIV, and 27 pathogens were detected in the BALF of 30 PLHIV by mNGS, among which 15 PLHIV were found to have multiple microbial infections (at least 3 pathogens). Pneumocystis jirovecii, human herpesvirus type 5, and human herpesvirus type 4 were the most common pathogen types.
CONCLUSIONS
For PLHIV with suspected pulmonary infections, mNGS is capable of rapidly and accurately identifying the pathogen causing the pulmonary infection, which contributes to implement timely and accurate anti-infective treatment.
Topics: Humans; High-Throughput Nucleotide Sequencing; Metagenomics; Male; Female; HIV Infections; Retrospective Studies; Bronchoalveolar Lavage Fluid; Adult; Middle Aged; China; Coinfection; Respiratory Tract Infections
PubMed: 38774626
DOI: 10.3389/fcimb.2024.1395239 -
Biomedicine & Pharmacotherapy =... Jun 2024Penicilazaphilone C (PAC) is hypothesized to potentially serve as a therapeutic treatment for allergic airway inflammation by inhibiting the NLRP3 inflammasome and...
AIMS
Penicilazaphilone C (PAC) is hypothesized to potentially serve as a therapeutic treatment for allergic airway inflammation by inhibiting the NLRP3 inflammasome and reducing oxidative stress.
METHODS
An allergic asthma model was induced in female BALB/c mice of the OVA, OVA+PAC, OVA+PAC+LPS, and OVA+Dex groups by sensitizing and subsequently challenging them with OVA. The OVA+PAC and Normal+PAC groups were treated with PAC, while the OVA+PAC+LPS group also received LPS. The OVA+Dex group was given dexamethasone (Dex). Samples of serum, bronchoalveolar lavage fluid (BALF), and lung tissue were collected for histological and cytological analysis.
RESULTS
Allergic mice treated with PAC or Dex showed inhibited inflammation and mucus production in the lungs. There was a decrease in the number of inflammatory cells in the BALF, lower levels of inflammatory cytokines in the serum and BALF, and a reduction in the protein expression of NLRP3, ASC, cleaved caspase-1, IL-1β, activated gasdermin D, MPO, Ly6G, and ICAM-1. Additionally, oxidative stress was reduced, as shown by a decrease in MDA and DCF, but an increase in SOD and GSH. Treatment with PAC also resulted in a decrease in pulmonary memory CD4+ T cells and an increase in regulatory T cells. However, the positive effects seen in the PAC-treated mice were reversed when the NLRP3 inflammasome was activated by LPS, almost returning to the levels of the Sham-treated mice.
SIGNIFICANCE
PAC acts in a similar way to anti-allergic inflammation as Dex, suggesting it may be a viable therapeutic option for managing allergic asthma inflammation.
Topics: Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Mice, Inbred BALB C; Female; Inflammasomes; Asthma; Bronchoalveolar Lavage Fluid; Mice; Lung; Oxidative Stress; Ovalbumin; Cytokines; Inflammation; Disease Models, Animal; Dexamethasone; Anti-Inflammatory Agents
PubMed: 38772153
DOI: 10.1016/j.biopha.2024.116788 -
Infection and Immunity Jun 2024Polymyxin resistance in carbapenem-resistant bacteria is associated with high morbidity and mortality in vulnerable populations throughout the world. Ineffective...
Polymyxin resistance in carbapenem-resistant bacteria is associated with high morbidity and mortality in vulnerable populations throughout the world. Ineffective antimicrobial activity by these last resort therapeutics can occur by transfer of , a plasmid-mediated resistance gene, causing modification of the lipid A portion of lipopolysaccharide (LPS) and disruption of the interactions between polymyxins and lipid A. Whether this modification alters the innate host immune response or carries a high fitness cost in the bacteria is not well established. To investigate this, we studied infection with (KP) ATCC 13883 harboring either the plasmid (p) or the vector control (pBCSK) ATCC 13883. Bacterial fitness characteristics of acquisition were evaluated. Differentiated human monocytes (THP-1s) were stimulated with KP bacterial strains or purified LPS from both parent isolates and isolates harboring . Cell culture supernatants were analyzed for cytokine production. A bacterial pneumonia model in WT C57/BL6J mice was used to monitor immune cell recruitment, cytokine induction, and bacterial clearance in the bronchoalveolar lavage fluid (BALF). Isolates harboring had increased colistin MIC compared to the parent isolates but did not alter bacterial fitness. Few differences in cytokines were observed with purified LPS from expressing bacteria . However, in a mouse pneumonia model, no bacterial clearance defect was observed between p-harboring KP and parent isolates. Consistently, no differences in cytokine production or immune cell recruitment in the BALF were observed, suggesting that other mechanisms outweigh the effect of these lipid A mutations in LPS.
Topics: Animals; Klebsiella pneumoniae; Colistin; Lipid A; Immunity, Innate; Mice; Klebsiella Infections; Disease Models, Animal; Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Pneumonia, Bacterial; Mice, Inbred C57BL; Cytokines; Bronchoalveolar Lavage Fluid; Female
PubMed: 38771050
DOI: 10.1128/iai.00016-24