-
BMJ Open Quality May 2024Sick preterm neonates are most vulnerable to developing skin injuries. Despite sound knowledge and application of evidence-based practices for preventing medical...
INTRODUCTION
Sick preterm neonates are most vulnerable to developing skin injuries. Despite sound knowledge and application of evidence-based practices for preventing medical adhesive-related skin injury (MARSI), the incidence of MARSI was 30 events per 1000 adhesive application days in our unit.
AIMS AND OBJECTIVES
We aimed to reduce the median MARSI rate from the existing 30 per 1000 MARSI days to <5 per 1000 MARSI over 5 months from June 2023 to October 2023.
MATERIAL & METHODS
With the point-of-care quality improvement (QI) approach, a prospective study was planned to reduce the incidence of MARSI among sick very preterm newborns (<32 weeks gestational age) and eventually improve overall skin condition during hospital stay. Sequential Plan-Do-Study-Act cycles were implemented based on the identified risk factors recognised during recurring team discussions.
RESULTS
We demonstrated a reduction in the MARSI rate from 30 events per 1000 adhesive applications (during baseline assessment) to zero events per 1000 adhesive applications at the end of the study period. It was temporally related to the assessment of skin risk stratification at admission using a validated tool, regular assessment of neonatal skin condition score based on the skin risk stratification, and reinforcement of MARSI prevention bundle by application of barrier spray. Awareness regarding 'skin injury prevention' bundles was continually generated among healthcare professionals. The MARSI rate remained <5 events per adhesive application in the sustenance phase over 6 months.
CONCLUSION
Implementing evidence-based skin care practices resulted in a significant reduction in iatrogenic cutaneous injury events in very preterm neonates.
Topics: Humans; Infant, Newborn; Quality Improvement; Prospective Studies; Intensive Care Units, Neonatal; Skin; Infant, Premature; Female; Male; Adhesives; Incidence
PubMed: 38816009
DOI: 10.1136/bmjoq-2023-002697 -
ELife May 2024Neurexins play diverse functions as presynaptic organizers in various glutamatergic and GABAergic synapses. However, it remains unknown whether and how neurexins are...
Neurexins play diverse functions as presynaptic organizers in various glutamatergic and GABAergic synapses. However, it remains unknown whether and how neurexins are involved in shaping functional properties of the glycinergic synapses, which mediate prominent inhibition in the brainstem and spinal cord. To address these issues, we examined the role of neurexins in a model glycinergic synapse between the principal neuron in the medial nucleus of the trapezoid body (MNTB) and the principal neuron in the lateral superior olive (LSO) in the auditory brainstem. Combining RNAscope with stereotactic injection of AAV-Cre in the MNTB of neurexin1/2/3 conditional triple knockout mice, we showed that MNTB neurons highly express all isoforms of neurexins although their expression levels vary remarkably. Selective ablation of all neurexins in MNTB neurons not only reduced the amplitude but also altered the kinetics of the glycinergic synaptic transmission at LSO neurons. The synaptic dysfunctions primarily resulted from an impaired Ca sensitivity of release and a loosened coupling between voltage-gated Ca channels and synaptic vesicles. Together, our current findings demonstrate that neurexins are essential in controlling the strength and temporal precision of the glycinergic synapse, which therefore corroborates the role of neurexins as key presynaptic organizers in all major types of fast chemical synapses.
Topics: Animals; Mice, Knockout; Glycine; Mice; Trapezoid Body; Synaptic Transmission; Neural Cell Adhesion Molecules; Superior Olivary Complex; Brain Stem; Synapses; Neurons; Cell Adhesion Molecules, Neuronal; Nerve Tissue Proteins; Neurexins; Calcium-Binding Proteins
PubMed: 38814174
DOI: 10.7554/eLife.94315 -
Turkish Journal of Medical Sciences 2023Atherosclerosis is significantly influenced by endothelial cell activation and dysfunction. Studies have demonstrated the substantial presence of fibronectin (Fn) within...
BACKGROUND/AIM
Atherosclerosis is significantly influenced by endothelial cell activation and dysfunction. Studies have demonstrated the substantial presence of fibronectin (Fn) within atherosclerotic plaques, promoting endothelial inflammation and activation. However, cellular Fn (cFn) secreted by various cell types, including endothelial cells and smooth muscle cells, and plasma Fn (pFn) produced by hepatocytes. They are distinct forms of Fn that differ in both structure and function. The specific contribution of different types of Fn in promoting endothelial cell activation and dysfunction remain uncertain. Therefore, this study aimed to investigate the respective roles of pFn and endothelial cell-derived Fn (Fn) in promoting endothelial cell activation and dysfunction.
MATERIALS AND METHODS
Initially, endothelial cell injury was induced by exposing the cells to oxidized low-density lipoprotein (ox-LDL) and subsequently we generated a mutant strain of aortic endothelial cells with Fn knockdown (Fn). The impact of the Fn arel the addition of pFn on the expression levels of inflammatory factors, vasoconstrictors, and diastolic factors were compared.
RESULTS
The results showed that the Fn significantly inhibited ox-LDL-induced intercellular adhesion molecule 1 (ICAM-1, p < 0.05), vascular cell adhesion molecule (VCAM-1, p < 0.05), and endothelin (p < 0.05) expression, and nuclear factor kappa-B (NFκB, p < 0.05) activation. These results implied that Fn inhibited both endothelial cell activation and dysfunction. Surprisingly, the addition of pFn significantly inhibited the ox-LDL-induced ICAM-1 (p < 0.05), VCAM-1 (p < 0.05), and endothelin (p < 0.05) expression and NFκB (p < 0.05) activation. Implying that pFn inhibits endothelial cell activation and dysfunction. Additionally, the study revealed that ox-LDL stimulation enhanced the production of excessive nitric oxide, leading to severe endothelial cell damage.
CONCLUSION
Aortic Fn promotes endothelial cell activation and endothelial dysfunction, whereas pFn inhibits ox-LDL-induced endothelial cell activation and endothelial dysfunction.
Topics: Fibronectins; Lipoproteins, LDL; Endothelial Cells; Humans; Vascular Cell Adhesion Molecule-1; Intercellular Adhesion Molecule-1; Endothelium, Vascular; Cells, Cultured; NF-kappa B
PubMed: 38813506
DOI: 10.55730/1300-0144.5735 -
Turkish Journal of Medical Sciences 2023Surfactant is a surface-active substance that, in addition to its detergent effect, also has effects that reduce inflammation and fibrosis. Because of these effects, it...
BACKGROUND/AIM
Surfactant is a surface-active substance that, in addition to its detergent effect, also has effects that reduce inflammation and fibrosis. Because of these effects, it was aimed herein to investigate the effect of intraperitoneal surfactant application on preventing postoperative peritoneal adhesion formation in a uterine horn adhesion model.
MATERIALS AND METHODS
Twenty-one Wistar albino rats were randomly divided into 3 groups (G1-G3), as follows: G1 (n = 7): control group. The abdomen was opened and then closed; G2 (n = 7): adhesion group. The abdomen was opened. Then, a 2-cm linear incision was made over the right uterine horn, 2 mL of isotonic saline was administered intraperitoneally, and the abdomen was closed; and G3 (n = 7): treatment group. The abdomen was opened, a 2-cm linear incision was made over the right uterine horn, 2 mL (70 mg/kg) of surfactant was administered intraperitoneally, and the abdomen was closed. After 15 days, the rats were euthanized, the abdomens were reopened, and adhesion scoring was performed. After the right uterine horns were removed and fixed with 10% formalin, appropriate sections were taken from the traumatized tissue, stained with Masson's trichrome, and fibrosis and inflammation scoring were performed.
RESULTS
The adhesion area and intensity were significantly higher in G2 than in G1 and G3 (p = 0.001) and were similar in G1 and G3 (p = 0.165). While fibrosis and inflammation were significantly higher in G2 than in G1 and G3 (p = 0.001), there was no difference between G1 and G3 (p = 0.5).
CONCLUSION
Intraperitoneal surfactant administration at a dose of 70 mg/kg was found to be effective in preventing intraabdominal adhesion formation in a rat uterine horn model.
Topics: Animals; Tissue Adhesions; Rats, Wistar; Female; Surface-Active Agents; Rats; Postoperative Complications; Injections, Intraperitoneal; Uterus; Disease Models, Animal
PubMed: 38813488
DOI: 10.55730/1300-0144.5752 -
Frontiers in Molecular Neuroscience 2024The synaptic adhesion molecule neuroligin-1 (NLGN1) is involved in the differentiation of excitatory synapses, but the precise underlying molecular mechanisms are still...
INTRODUCTION
The synaptic adhesion molecule neuroligin-1 (NLGN1) is involved in the differentiation of excitatory synapses, but the precise underlying molecular mechanisms are still debated. Here, we explored the role of NLGN1 tyrosine phosphorylation in this process, focusing on a subset of receptor tyrosine kinases (RTKs), namely FGFR1 and Trks, that were previously described to phosphorylate NLGN1 at a unique intracellular residue (Y782).
METHODS
We used pharmacological inhibitors and genetic manipulation of those RTKs in dissociated hippocampal neurons, followed by biochemical measurement of NLGN1 phosphorylation and immunocytochemical staining of excitatory synaptic scaffolds.
RESULTS
This study shows that: (i) the accumulation of PSD-95 at NLGN1 clusters induced by neurexin crosslinking is reduced by FGFR and Trk inhibitors; (ii) the increase in PSD-95 puncta caused by NLGN1 over-expression is impaired by FGFR and Trk inhibitors; (iii) TrkB activation by BDNF increases NLGN1 phosphorylation; and (iv) TrkB knock-down impairs the increase of PSD-95 puncta caused by NLGN1 over-expression, an effect which is not seen with the NLGN1 Y782A mutant.
DISCUSSION
Together, our data identify TrkB as one of the major RTKs responsible for NLGN1 tyrosine phosphorylation, and reveal that TrkB activity is necessary for the synaptogenic effects of NLGN1.
PubMed: 38813439
DOI: 10.3389/fnmol.2024.1359067 -
International Journal of General... 2024Gallstone disease (GS) is an important risk factor for Gallbladder cancer (GBC). However, the mechanisms of the progression of GS to GBC remain unclear. Long non-coding...
BACKGROUND
Gallstone disease (GS) is an important risk factor for Gallbladder cancer (GBC). However, the mechanisms of the progression of GS to GBC remain unclear. Long non-coding RNA (lncRNA), modulates DNA/RNA/proteins at epigenetic, pre-transcriptional, transcriptional and posttranscriptional levels, and plays a potential therapeutic role in various diseases. This study aims to identify lncRNAs that have a potential impact on GS-promoted GBC progression.
METHODS AND RESULTS
Six GBC patients without GS, six normal gallbladder tissues, nine gallstones and nine GBC patients with GS were admitted to our hospital. The next-generation RNA-sequencing was performed to analyze differentially expressed (DE) lncRNA and messenger RNA (mRNA) in four groups. Then overlapping and specific molecular signatures were analyzed. We identified 29 co-DEGs and 500 co-DElncRNAs related to gallstone or GBC. The intersection and concatenation of co-DEGs and co-DElncRNA functionally involved in focal adhesion, Transcriptional misregulation in cancers, Protein digestion and absorption, and ECM-receptor interaction signaling pathways may contribute to the development of gallbladder cancer. Further exploration is necessary for early diagnosis and the potential treatment of GBC. FXYD2, MPZL1 and PAH were observed in both co-DEGs and co-DElncRNA and validated by qRT-PCR.
CONCLUSION
Our data identified a series of DEGs and DElncRNAs, which were involved in the progression of GBC and GS-related metabolism pathways. Compared to GBC, the GS profile was more similar to para-tumor tissues in transcriptome level and lower risk of cancer. Further exploration is necessary from GBC patients with different periods of follow-up gallstone.
PubMed: 38813241
DOI: 10.2147/IJGM.S442379 -
Frontiers in Bioengineering and... 2024To study the ability of theaflavin-3,3'-digallate (TF3)/ethanol solution to crosslink demineralized dentin collagen, resist collagenase digestion, and explore the...
OBJECTIVES
To study the ability of theaflavin-3,3'-digallate (TF3)/ethanol solution to crosslink demineralized dentin collagen, resist collagenase digestion, and explore the potential mechanism.
METHODS
Fully demineralized dentin blocks were prepared using human third molars that were caries-free. Then, these blocks were randomly allocated into 14 separate groups (n = 6), namely, control, ethanol, 5% glutaraldehyde (GA), 12.5, 25, 50, and 100 mg/ml TF3/ethanol solution groups. Each group was further divided into two subgroups based on crosslinking time: 30 and 60 s. The efficacy and mechanism of TF3's interaction with dentin type I collagen were predicted through molecular docking. The cross-linking, anti-enzymatic degradation, and biomechanical properties were studied by weight loss, hydroxyproline release, scanning/transmission electron microscopy (SEM/TEM), zymography, surface hardness, thermogravimetric analysis, and swelling ratio. Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy were utilized to explore its mechanisms. Statistical analysis was performed using one and two-way analysis of variance and Tukey's test.
RESULTS
TF3/ethanol solution could effectively crosslink demineralized dentin collagen and improve its resistance to collagenase digestion and biomechanical properties ( < 0.05), showing concentration and time dependence. The effect of 25 and 50 mg/ml TF3/ethanol solution was similar to that of 5% GA, whereas the 100 mg/mL TF3/ethanol solution exhibited better performance ( < 0.05). TF3 and dentin type I collagen are mainly cross-linked by hydrogen bonds, and there may be covalent and hydrophobic interactions.
CONCLUSION
TF3 has the capability to efficiently cross-link demineralized dentin collagen, enhancing its resistance to collagenase enzymatic hydrolysis and biomechanical properties within clinically acceptable timeframes (30 s/60 s). Additionally, it exhibits promise in enhancing the longevity of dentin adhesion.
PubMed: 38812911
DOI: 10.3389/fbioe.2024.1401032 -
Ultrasound International Open 2024Arthroscopy is one of the most common interventions in orthopedics. Hence it is important to train users early in order to ensure the safest possible identification...
Arthroscopy is one of the most common interventions in orthopedics. Hence it is important to train users early in order to ensure the safest possible identification of access portals (AP). This prospective study aimed to compare a palpatory (PalpMethod) with a sonographic (SonoMethod) method for AP location in the shoulder and knee joints. The study included trainee doctors (n=68) attending workshops (lasting approx. 90 minutes). In these workshops a teaching video initially demonstrated the PalpMethod and SonoMethod of AP identification. An experienced operator first marked the access portals on the test subject with a UV pen (determined ideal point [DIP]). Adhesive film was then affixed to the puncture regions. Subsequently participants marked on shoulders and knees first the point determined by palpation, then the point determined by sonography. Analysis involved DIP visualization with a UV lamp and employed a coordinate system around the central DIP. In addition, participants completed an evaluation before and after the workshop. The analysis included 324 measurements (n=163 shoulders and n= 161 knees). The majority of participants had not previously attended any courses on manual examination (87.9%) or musculoskeletal ultrasound (93.9%). Overall, the markings participants made on the shoulder using the SonoMethod were significantly closer to the DIP than those made by the PalpMethod (Palp 18.8mm ± 14.5mm vs. Sono 11.2mm ± 7.2mm; p<0.001). On the knee, however, the markings made by the PalpMethod were significantly closer to the DIP overall (Palp 8.0mm ± 3.2mm vs. Sono 12.8mm ± 5.2mm; p<0.001). Conclusion The results show that the SonoMethod produces more accurate markings on the shoulder, while the PalpMethod is superior for the knee.
PubMed: 38812890
DOI: 10.1055/a-2271-0098 -
Frontiers in Microbiology 2024Folate supplementation is crucial for the human body, and the chemically synthesized folic acid might have undesirable side effects. The use of molecular breeding...
INTRODUCTION
Folate supplementation is crucial for the human body, and the chemically synthesized folic acid might have undesirable side effects. The use of molecular breeding methods to modify the genes related to the biosynthesis of folate by probiotics to increase folate production is currently a focus of research.
METHODS
In this study, the folate-producing strain of B1-28 was isolated from human breast milk, and the difference between B1-28 and gene deletion strain was investigated by phenotyping, probiotic evaluation, metabolism and transcriptome analysis.
RESULTS
The results showed that the folate producted by the was 2-3 folds that of the B1-28. Scanning electron microscope showed that had rougher surface, and the acid-producing capacity ( = 0.0008) and adhesion properties ( = 0.0096) were significantly enhanced than B1-28. Transcriptomic analysis revealed that differentially expressed genes were mainly involved in three pathways, among which the biosynthesis of ribosome and aminoacyl-tRNA occurred in the key metabolic pathways. Metabolomics analysis showed that affected 5 metabolic pathways, involving 89 different metabolites.
DISCUSSION
In conclusion, the editing of a key gene of in folate biosynthesis pathway provides a feasible pathway to improve folate biosynthesis in breast milk-derived probiotics.
PubMed: 38812695
DOI: 10.3389/fmicb.2024.1402654 -
Frontiers in Bioscience (Landmark... May 2024Osteosarcoma (OS) is the most prevalent orthopedic malignancy with a dismal prognosis. Disulfidptosis-related lncRNAs (DRLncs) may be related to the progression of OS,...
BACKGROUND
Osteosarcoma (OS) is the most prevalent orthopedic malignancy with a dismal prognosis. Disulfidptosis-related lncRNAs (DRLncs) may be related to the progression of OS, but their potential molecular regulatory role is still unclear.
METHODS
Based on the data collected from The Cancer Genome Atlas (TCGA), we conducted correlation analysis and the univariate Cox analysis to screen prognosis-related DRLncs, followed by developing genotyping patterns and corresponding classifier. Subsequently, the survival analysis, enrichment analysis, drug sensitivity analysis and immune infiltration analysis were performed. Afterward, multivariate Cox regression was used to construct a risk model, which was further validated by the receiver operating characteristic (ROC) curve. The aberrant expression of hub DRLncs in OS was validated using the Reverse Transcription Polymerase Chain Reaction (RT-qPCR) assay.
RESULTS
We identified 262 DRLncs and eleven prognosis-related DRLncs through filtering. We then constructed two distinct expression patterns of prognosis-related DRLncs and developed a classifier. We obtained 393 differentially expressed genes (DEGs) between different subtypes, which were significantly enriched in biological processes related to the extracellular matrix, integrin binding, focal adhesion, and Wnt signaling pathways. Through immune infiltration analysis, the activated CD4 memory T cells, resting natural killer (NK) cells, M1 macrophages, and resting dendritic cells (DC) were observed to exhibit different abundance in distinct subtypes. In the drug sensitivity analysis, tamoxifen showed a promising effect for drug-resistant OS. Furthermore, we identified five hub DRLncs and constructed a risk model. The RT-qPCR confirmed the aberrant expression of five hub DRLncs in OS.
CONCLUSIONS
The present study identified DRLncs in OS, and conducted a comprehensive investigation of DRLncs-related expression patterns, survival status, immune landscape and drug sensitivity to reveal the difference in prognostic, pharmacological and immunological phenotype characteristics between distinct subtypes. Additionally, we developed a risk model to predict the prognosis, and constructed a genotyping classifier to predict the above phenotype characteristics in OS.
Topics: Humans; Osteosarcoma; RNA, Long Noncoding; Prognosis; Bone Neoplasms; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor; Genotype; Gene Expression Profiling; Tumor Microenvironment; Female; Male
PubMed: 38812298
DOI: 10.31083/j.fbl2905193