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Ware, Alicia; Johnston, William; Delaney, Christopher; Butcher, Mark C.; Ramage, Gordon; Price, Lesley; Butcher, John; Kean, Ryan
doi: 10.1111/apm.70022pmid: 40194790
Candida auris is an enigmatic fungal pathogen, recently elevated as a critical priority group pathogen by the World Health Organisation, linked with its ability to cause outbreaks within nosocomial care units, facilitated through environmental persistence. We investigated the susceptibility of phenotypically distinct C. auris isolates to sodium hypochlorite (NaOCl), and evaluated the role of biofilms in surviving disinfection using a dry‐surface biofilm (DSB) model and transcriptomic profiling. Planktonic cells were tested for susceptibility to NaOCl, with biofilm formation using the 12‐day DSB model, assessed using viable counts, biomass assays and microscopy. Disinfection efficacy was assessed using clinical protocols of 500–1,000 ppm for 1–5 min. RNA sequencing was performed on untreated DSBs in comparison to planktonic cells. Isolates were found to be susceptible planktonically, but grew NaOCl‐tolerant biofilms, with only 2–4 log10 reductions in viable cells observed at highest concentrations. Transcriptomics identified DSB upregulation of ABC transporters and iron acquisition pathways relative to planktonic cells. Our findings optimized a DSB protocol in which C. auris can mediate tolerance to NaOCl disinfection, suggesting a lifestyle through which this problematic yeast can environmentally persist. Mechanistically, it has been shown for the first time that upregulation of small‐molecule and iron transport pathways are potential facilitators of environmental survival.
Zhang, Weiqiang; Shuai, Wenjun; Liu, Chunlan; Lai, Wenxia; Wang, Xiaohua
doi: 10.1111/apm.70020pmid: 40159712
This study aims to explore the clinical efficacy of calcium gluconate combined with ergometrine maleate in preventing and treating uterine atony‐induced postpartum hemorrhage (PPH) and its impacts on coagulation function. Ninety‐six postpartum women with uterine atony were randomly assigned into a study group and a control group (48 cases each) using a double‐blind method. The control group received calcium gluconate, while the study group received calcium gluconate combined with ergometrine maleate. Postpartum blood loss at 2 and 24 h, hemostasis time, hemoglobin levels, red blood cell (RBC) count, coagulation indices (PT, TT, APTT, D‐D, FIB), inflammatory markers (CRP, IL‐6, PCT), labor duration, hospital stay, menstruation recovery, stress‐related indicators, and blood viscosity were compared. The study group had significantly lower postpartum blood loss, shorter labor stages, and higher hemoglobin levels and RBC counts at 24 h (p < 0.05). Postpartum, PT, TT, APTT, D‐D, inflammatory markers, and stress indicators were lower, while FIB was higher in the study group (p < 0.05). The combination of ergometrine maleate and calcium gluconate effectively reduces PPH, improves stress‐related inflammation, and shortens hemostasis time, demonstrating significant clinical benefits.
doi: 10.1111/apm.70024pmid: 40214088
The phrase ‘All models are wrong but some are useful’ spoken by George Box in 1976 is as relevant today as ever. Modern research relies heavily on models and the use of in vitro models is the cornerstone of developing novel treatments for various infectious diseases. Simple growth media have been, and still are, heavily used when performing research involving biofilms and infectious pathogens. However, using modern technologies, large discrepancies are now being revealed between bacteria grown in simple media versus those grown in more authentic media. These discrepancies can lead to significant differences in bacterial tolerances, growth patterns, biofilm formation abilities, etc. Hence, if the aim is to replicate the in vivo situation in a laboratory setting, the creation of realistic simulated bodily fluids should be prioritised. This paper presents a range of simulated human fluids from various body sites where infections often occur. Bacterial behaviour has been evaluated in all these media and is often compared to a simple growth medium counterpart. In all instances, significant differences are observed which might lead to important discrepancies, particularly in potential treatment efficiency. We hope this may serve as inspiration for any researcher doing in vitro work, attempting to mimic reality.
doi: 10.1111/apm.70026pmid: 40259167
RETRACTION: C. Cayrou, B. Sambe, F. Armougom, D. Raoult, and M. Drancourt, “Molecular Diversity of the Planctomycetes in the Human Gut Microbiota in France and Senegal,” APMIS 121, no. 11 (2013): 1082–1090, https://doi.org/10.1111/apm.12087.
Allkja, Jontana; Bakri, Ahmed; Short, Bryn; Gilmour, Andrew; Brown, Jason L.; Bal, Abhijit M.; Newby, Kelly J. M.; Jenkins, Toby; Short, Rob D.; Williams, Craig; Ramage, Gordon
doi: 10.1111/apm.70025pmid: 40264255
Diabetic foot ulcers (DFUs) are common complications for diabetic patients, often exacerbated by complex polymicrobial biofilm infections. While the majority of DFU studies are bacterial focused, fungi have also been identified. This study aims to investigate the prevalence of fungi in DFUs, as well as their potential role and influence on persistence and wound healing. Consecutive DFU swabs were collected from 128 patients (n = 349). Fungal positivity was assessed using enhanced culture and real‐time qPCR. Routine microbiology cultures were carried out as part of standard care in the clinics, and their results were then compared to our laboratory investigation. Routine and enhanced culture resulted in similar rates of fungal detection (~9%), whereas qPCR resulted in a higher rate of detection (31%). Notably, the predominant yeast Candida parapsilosis was present in ischaemic and penetrating bone wounds. These findings support existing evidence of fungal presence in DFUs. We demonstrated that routine diagnostic methods are sufficient for fungal detection, but enhanced culture methods allow for more precise fungal identification. Finally, while fungal presence does not appear to impact patient outcomes in our study, their role within these infections remains poorly understood, and further studies are needed to fully understand their relationship to the microbiome.
Chen, Trina; Mennander, Ari; Paavonen, Timo; Kholová, Ivana
doi: 10.1111/apm.70023pmid: 40170509
This study investigated the distinguishing characteristics between acute type A aortic dissection (ATAAD) and aortic wall dilatation. Utilizing systematic histopathology criteria from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology consensus statement, the analysis focused on degeneration, atherosclerosis, and inflammation in patients undergoing surgery in a Finnish tertiary care hospital. The study included 156 patients, those undergoing surgery for ATAAD (n = 116) and those with dilatation (n = 40). Despite similar clinical characteristics, histological analysis of the aortic wall indicated a higher overall degeneration in ATAAD compared to dilatation (2.4 ± 0.6 vs. 1.9 ± 0.8, Point score unit (PSU), p < 0.001). Findings included increased intralamellar mucoid extracellular matrix accumulation (69 vs. 32, p = 0.020; extent 2.0 ± 0.3 vs. 1.7 ± 0.5, PSU, p < 0.001; severity 1.8 ± 0.6 vs. 1.5 ± 0.5, PSU, p = 0.005) elastic fiber thinning (68 vs. 9, p = 0.001; extent 1.0 ± 0.9 vs. 0.4 ± 0.8, PSU, p < 0.001; severity 0.8 ± 0.8 vs. 0.4 ± 0.8, PSU, p = 0.001), elastic fiber disorganization (89 vs. 21, p = 0.005; extent 1.2 ± 0.8 vs. 0.9 ± 0.9, PSU, p = 0.029) and laminar medial collapse (64 vs. 6, p < 0.001; type 0.7 ± 0.7 vs. 0.2 ± 0.4, PSU, p < 0.001; extent 0.9 ± 0.9 vs. 0.9 ± 0.9, PSU, p < 0.001) in ATAAD compared to dilatation. Elastic fiber pathology and laminar medial collapse are distinct features of ATAAD compared to aortic dilatation in patients undergoing ascending aorta surgery.
Wang, Chen; Liu, Jiangwen; Wu, Yali; Cai, Chen; Chai, Zhiwei; Jia, Ping; Yuan, Yueyue; Jiang, Zhixin
doi: 10.1111/apm.70021pmid: 40177797
Hepatocellular carcinoma (HCC) is a major cause of cancer‐related deaths worldwide. Aurora kinase B (AURKB), a critical regulator of mitosis, has been implicated in cancer progression, though its precise role in HCC remains unclear. In this study, AURKB expression was found to be significantly elevated in HCC tissues and cell lines compared to controls, as validated by GEPIA and ENCORI databases. Functional assays revealed that AURKB knockdown reduced cell proliferation, invasion, and migration, while increasing apoptosis. Furthermore, suppression of AURKB affected epithelial‐mesenchymal transition (EMT) markers, decreasing vimentin and N‐cadherin levels and increasing E‐cadherin expression. In vivo, a xenograft mouse model demonstrated that tumors derived from AURKB‐silenced cells exhibited reduced growth and fewer lung metastases. Histological and immunohistochemical analyses showed lower levels of Ki‐67, MMP‐9, and EMT markers in these tumors, alongside increased E‐cadherin. These findings highlight AURKB's critical role in promoting HCC progression, metastasis, and EMT regulation. Overexpression of AURKB was associated with poor prognosis, suggesting it could serve as a potential biomarker and therapeutic target for liver cancer. Overall, targeting AURKB may provide a novel approach to inhibit HCC growth and metastasis, improving patient outcomes.
Ataollahi, Mohammad Reza; Atashzar, Mohammad Reza; Asad, Ali Ghanbari; Tabar, Mohammad Mahdi Mokhtari; Amani, Davar
doi: 10.1111/apm.13512pmid: 40254968
Tumor‐associated antigens that can induce antitumor immune responses as well as endogenous microRNAs are found in tumor‐derived exosomes (TEXs). The objective of the current investigation was to assess the ability of MicroRNA (miR)‐211‐enriched TEX (TEXomiR) to induce antitumor immune responses in a melanoma mouse model. B16F10 melanoma cells in culture were used to extract exosomes. MiR‐211 mimics were introduced into the exosomes using a modified calcium chloride technique. In C57BL/6 mice, the effects of TEXomiR were assessed by measuring tumor growth, weight, immune cell populations in the tumor and spleen and cytokine release. PBS, TEX, or TEXomiR were given subcutaneously to mice three times every 3 days until tumors grew to a size of 100 mm3. In vivo experiments using B16F10‐bearing mice indicated that, in comparison with unmodified TEX and PBS, TEXomiR administration boosted improved antitumor immune responses. There was a notable increase in survival time. Mice treated with TEXomiR showed suppression of tumor development. Tumor tissue had much lower ratios of T regularity/CD8 T cells and CD4/CD8 T cells. Our findings showed that TEXomiR stimulates antitumor immune responses and that tumor‐derived exosomes are an effective vehicle for miR‐211 mimic delivery.
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