Tissue Lesions Research Articles

Cannabidiol Alleviates Oral Mucositis by Inhibiting PI3K/Akt/NF-κB-Mediated Pyroptosis.

Cannabidiol (CBD), extracted from Cannabis sativa, has anticancer, anti-inflammation, and analgesic effects. Nevertheless, its therapeutic effect and the mechanism by which it alleviates oral mucositis (OM) remain unclear. To explore the impact of CBD on OM in mice and on human oral keratinocyte (HOK) cells. Expiremental study. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, GeneCard, DisGeNET, and Gene Expression Omnibus databases were used to conduct therapeutic target gene screening for drugs against OM. Cytoscape software was used to build networks linking components, targets, and diseases. The STRING database facilitated analysis of intertarget action relationships, and the target genes were analyzed for Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Occurrence of serum inflammation-related factors, hematoxylin and eosin staining, and immunohistochemistry were used to assess OM injury. Cell proliferation, migration, pyroptosis, and apoptosis of HOK cells under different treatments were assessed. Molecular mechanisms were elucidated through western blot and quantitative real-time polymerase chain reaction analyses. A total of 49 overlapping genes were pinpointed as potential targets, with NF-κB1, PIK3R1, NF-κBIA, and AKT1 being recognized as hub genes among them. Additionally, the PI3K/Akt/NF-κB and interleukin-17 signaling pathways were identified as relevant. Our in vivo experiments showed that CBD significantly reduced the proportion of lesion area, mitigated oral mucosal tissue lesions, and downregulated the expression levels of genes and levels of proteins, including NLRP3, P65, AKT, and PI3K. In vitro experiments indicated that CBD enhanced HOK cell proliferation and migration and reduced apoptosis through inhibition of the PI3K/Akt/NF-κB signaling pathway and pyroptosis. Our findings suggest a novel mechanism for controlling OM, in which CBD suppresses the PI3K/Akt/NF-κB signaling pathway and pyroptosis, thereby mitigating OM symptoms.

Somatic RIT1 delins in arteriovenous malformations hyperactivate RAS-MAPK signaling amenable to MEK inhibition.

Arteriovenous malformations (AVM) are benign vascular anomalies prone to pain, bleeding, and progressive growth. AVM are mainly caused by mosaic pathogenic variants of the RAS-MAPK pathway. However, a causative variant is not identified in all patients. Using ultra-deep sequencing, we identified novel somatic RIT1 delins variants in lesional tissue of three AVM patients. RIT1 encodes a RAS-like protein that can modulate RAS-MAPK signaling. We expressed RIT1 variants in HEK293T cells, which led to a strong increase in ERK1/2 phosphorylation. Endothelial-specific mosaic overexpression of RIT1 delins in zebrafish embryos induced AVM formation, highlighting their functional importance in vascular development. Both ERK1/2 hyperactivation in vitro and AVM formation in vivo could be suppressed by pharmacological MEK inhibition. Treatment with the MEK inhibitor trametinib led to a significant decrease in bleeding episodes and AVM size in one patient. Our findings implicate RIT1 in AVM formation and provide a rationale for clinical trials with targeted treatments.

Ultrasound fuzzy entropy imaging based on time-series signal for tissue characterization

This study proposed a parametric imaging method of fuzzy entropy based on time-series signal, which can enhance the contrast and augment the accuracy of the detection of lesions in soft tissue. Fuzzy entropy assesses the irregularity of ultrasound time-series data through the detection of similarities within the signal waveform. Applying fuzzy entropy in ultrasound tissue characterization can provide more tissue information. The sliding windows are performed to traverse across the whole image with the step of one pixel. The signal in the sliding window calculates the fuzzy entropy (FE), and the FE value is assigned to the window’s center pixel. The entropy image will be constructed after obtaining all fuzzy entropies. The performance of the proposed FE imaging was compared with weighted Shannon entropy (WSE) imaging and B-mode imaging by simulations, ex vivo experiments, and clinical data. FE imaging got superior lesion area prediction with the AUC of 0.959 ± 0.042 (p < 0.0001), the accuracy of 99.88 ± 0.09 % (p < 0.0001), and the contrast-to-noise ratio of 7.806 ± 4.476 (p < 0.001) in the thyroid nodule diagnostic tests. The results show that FE imaging significantly increases the contrast of the images. Compared with WSE, the FE imaging method has better sensitivity to disorder degree and better recovery ability of tissue information when the amplitude of the signal decreases or the change of signal properties is small. FE imaging considers the characteristics of ultrasound time series. It has a better recovery ability for ultrasound signals, which is a promising technique for soft tissue diagnosis and thermal ablation monitoring.

Loss of miR-145 promotes remyelination and functional recovery in a model of chronic central demyelination

Strategies for treating progressive multiple sclerosis (MS) remain limited. Here, we found that miR-145-5p is overabundant uniquely in chronic lesion tissues from secondary progressive MS patients. We induced both acute and chronic demyelination in miR-145 knockout mice to determine its contributions to remyelination failure. Following acute demyelination, no advantage to miR-145 loss could be detected. However, after chronic demyelination, animals with miR-145 loss demonstrated increased remyelination and functional recovery, coincident with altered presence of astrocytes and microglia within the corpus callosum relative to wild-type animals. This improved response in miR-145 knockout animals coincided with a pathological upregulation of miR-145-5p in wild-type animals with chronic cuprizone exposure, paralleling human chronic lesions. Furthermore, miR-145 overexpression specifically in oligodendrocytes (OLs) severely stunted differentiation and negatively impacted survival. RNAseq analysis showed altered transcriptome in these cells with downregulated major pathways involved in myelination. Our data suggest that pathological accumulation of miR-145-5p is a distinctive feature of chronic demyelination and is strongly implicated in the failure of remyelination, possibly due to the inhibition of OL differentiation together with alterations in other glial cells. This is mirrored in chronic MS lesions, and thus miR-145-5p serves as a potential relevant therapeutic target in progressive forms of MS.

Exploring the role of vitamin D-VDR pathway in pemphigus foliaceous: a novel perspective on disease pathogenesis.

Several auto-immune diseases have been linked to vitamin D deficiency as a contributing environmental factor. Its pleiotropic effects on the immune system, especially its essential role in maintaining immune tolerance, make the vitamin D pathway of great interest. In this study, we focused on Pemphigus foliaceous (PF) in Tunisian population. we aimed to quantify the Serum 25[OH]D levels using chemiluminescence assay and to analyze the differential expression of the VDR, CYP27B1 and CYP24A1 genes in the circulating blood cells and lesional skin tissue of PF patients using Q-PCR. A genetic explanation was then sought to explore any direct relationship between tag polymorphisms and the inherited features of PF. Results confirmed a vitamin D hypovitaminosis in Tunisian PF patients. Interestingly, a differential gene expression correlated to the disease stratification was noted. Indeed, at the systemic level, an upregulation of VDR and CYP27B1 genes was observed in healthy controls compared to PF patients. Notably, in lesional skin tissue, the clinical and serological remission phase was correlated with high transcriptional levels of the VDR gene and conversely a drop in expression of the CYP24A1 gene. Genetic analysis indicated the involvement of the most appealing polymorphisms, rs2228570 and poly (A) microsatellite, in PF etiopathogenesis. Indeed, CAC13 haplotype was associated with a higher risk of PF development. Our findings suggest that alterations in the vitamin D-VDR pathway may influence PF physiopathology, making this pathway a potential target for pharmacological modulation, especially for cortico-resistant PF patients.

O-267 Extracellular vesicles as biomarkers of endometriosis

Abstract Study question Can extracellular vesicles serve as biomarkers of endometriosis, particularly for stages I and II, which are difficult to detect by ultrasound? Summary answer Our findings suggest the feasibility of defining a protein signature of endometriosis based on EV cargoes. What is known already Endometriosis is characterised by intraperitoneal lesions of endometrial tissue. Although ultrasound detection of severe endometriosis is possible, the diagnosis of peritoneal lesions currently relies on invasive laparoscopy, which leads to a delay of 8-10 years. We have previously shown that peritoneal fluid (PF) of women with endometriosis contains endometriosis specific EVs. Traced in peripheral blood (PB), EVs could serve as biomarkers of endometriosis, particularly for stages I and II, which are difficult to detect by ultrasound. Study design, size, duration Women 18-45 years of age undergoing laparoscopic surgery for endometriosis or unrelated conditions were invited to participate in our study (HREC 20-159A/HREC 20-882A). Following informed consent, we collected PF and PB samples from n = 101 participants (n = 47 controls, n = 54 cases). Exclusion criteria were pregnancy, malignancy, and menopause. Participants/materials, setting, methods We processed PF and PB samples by differential ultracentrifugation and validated the presence of EVs by nanoparticle tracking analysis (NTA), Western blotting and transmission electron microscopy (TEM). EVs were analysed by untargeted, label-based quantitative proteomics using Tandem Mass Tags (TMT). Data analysis was performed using Proteome Discoverer v2.4 (Thermo Fisher) followed by statistical analysis using R. Candidate biomarker proteins were tested by traditional and automated Western blotting (WES, ProteinSimple). Main results and the role of chance We ascertained the identity of EVs by TEM and NTA (mode size 121.8 ± 18.0 nm (blood, n = 5) and 155.9 ± 37.2 (PF, n = 6)), and signals for syntenin and ALIX in immunoblots as well as expression of CD9, CD63 and CD81 in capture bead-flow cytometry. Proteomic analysis identified 9145 protein groups across all sample groups, with 602 significantly regulated between comparisons (adjusted P-value &amp;lt;0.05). In PF, 533 proteins changed significantly in abundance (245 up/288 down), while in blood, only four proteins changed in abundance. We tested the presence/absence of two of these as candidate markers on PB EV protein preparations from n = 32 samples to date; our best marker showed a sensitivity of 67% and a specificity of 90%; upon exclusion of severe endometriosis cases, sensitivity improved to 80%. Limitations, reasons for caution Because of the changes in vesicle composition and amounts with the menstrual cycle, we have to group the samples by menstrual cycle phase and disease severity. This leaves relatively small numbers per group per condition. Another limitation concerns the relatively small amount of sample liquid and thus, EVs available for analysis. Wider implications of the findings Our findings suggest the feasibility of defining a protein signature of endometriosis based on EV cargoes. A non-invasive clinical test would allow for earlier diagnosis and thus treatment of endometriosis. It would also allow patients to initiate fertility treatment early. Trial registration number not applicable

Role of MRI in Patellofemoral Pain Syndrome (Anterior Knee Pain)

Abstract Background MRI is a good diagnostic tool in identifying cartilage and soft tissue lesions as well as detecting underlying predisposing anatomical factors of patellar instability, it has a high specification for detecting the grades and the types of some of these diseases or factors that may predispose to them such as trochlear dysplasia and patella alta. Aim of the Work The aim of this study was to evaluate the role of MRI in diagnosis of Patellofemoralpain syndrome which is the most common cause of anterior knee pain. Patients and Methods This prospective study was done on patients referred from the orthopedic clinic to the department of radiodiagnosis, MRI unit at Ain Shams University hospitals.Thirty patients were included (18 females and 12 males) and their age ranged from 20 to 64 years. Conclusion This study shows that MRI is useful in detecting various predisposing anatomical factors of patellofemoral instability and associated lesions of knee joint thereby enabling orthopedic surgeons to treat joint pathology as well as correct underlying anatomical abnormality.

Highly Drug-Loaded Nanoaggregate Microparticles for Pulmonary Delivery of Cyclosporin A.

Nanoparticles have the advantages of improving the solubility of poorly water-soluble drugs, facilitating the drug across biological barriers, and reducing macrophage phagocytosis in pulmonary drug delivery. However, nanoparticles have a small aerodynamic particle size, which makes it difficult to achieve optimal deposition when delivered directly to the lungs. Therefore, delivering nanoparticles to the lungs effectively has become a popular research topic. Nanoaggregate microparticles were used as a pulmonary drug delivery strategy for the improvement of the bioavailability of cyclosporine A (CsA). The nanoaggregate microparticles were prepared with polyvinyl pyrrolidone (PVP) as the excipient by combining the anti-solvent method and spray drying process. The physicochemical properties, aerodynamic properties, in vivo pharmacokinetics and inhalation toxicity of nanoaggregate microparticles were systematically evaluated. The optimal nanoparticles exhibited mainly spherical shapes with the particle size and zeta potential of 180.52 nm and -19.8 mV. The nanoaggregate microparticles exhibited irregular shapes with the particle sizes of less than 1.6 µm and drug loading (DL) values higher than 70%. Formulation NM-2 as the optimal nanoaggregate microparticles was suitable for pulmonary drug delivery and probably deposited in the bronchiole and alveolar region, with FPF and MMAD values of 89.62% and 1.74 μm. In addition, inhaled NM-2 had C max and AUC0-∞ values approximately 1.7-fold and 1.8-fold higher than oral cyclosporine soft capsules (Neoral®). The inhalation toxicity study suggested that pulmonary delivery of NM-2 did not result in lung function damage, inflammatory responses, or tissue lesions. The novel nanoaggregate microparticles for pulmonary drug delivery could effectively enhance the relative bioavailability of CsA and had great potential for clinical application.

Spinal Infections? mNGS Combined with Microculture and Pathology for Answers.

This study evaluates the efficacy of metagenomic next-generation sequencing (mNGS) in diagnosing spinal infections and developing therapeutic regimens that combine mNGS, microbiological cultures, and pathological investigations. Data were collected from 108 patients with suspected spinal infections between January 2022 and December 2023. Lesion tissues were obtained via C-arm assisted puncture or open surgery for mNGS, conventional microbiological culture, and pathological analysis. Personalized antimicrobial therapies were tailored based on these findings, with follow-up evaluations 7 days postoperatively. The sensitivity and specificity of mNGS were assessed, along with its impact on treatment and prognosis. mNGS showed a significantly higher positive detection rate (61.20%) compared to conventional microbiological culture (30.80%) and PCT (28%). mNGS demonstrated greater sensitivity (79.41%) and negative predictive value (63.16%) than cultures (25% and 22.58%, respectively), with no significant difference in specificity and positive predictive value. Seven days post-surgery, a significant reduction in neutrophil percentage (NEUT%) was observed, though decreases in white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were not statistically significant. At the last follow-up, significant improved in Visual Analogue Scale (VAS) scores, Oswestry Disability Index (ODI), and Japanese Orthopaedic Association (JOA) scores were noted. mNGS outperforms traditional microbiological culture in pathogen detection, especially for rare and critical pathogens. Treatment protocols combining mNGS, microbiological cultures, and pathological examinations are effective and provide valuable clinical insights for treating spinal infections.

Association of Cortical Lesions With Regional Glutamate, GABA, N-Acetylaspartate, and Myoinositol Levels in Patients With Multiple Sclerosis.

Cortical lesions contribute to disability in multiple sclerosis (MS), but their impact on regional neurotransmitter levels remains to be clarified. We tested the hypothesis that cortical lesions are associated with regional glutamate and gamma-aminobutyric acid (GABA) concentrations within the affected cortical region. In this cross-sectional study, we used structural 7T MRI to segment cortical lesions and 7T proton MR-spectroscopy of the bilateral sensorimotor hand areas to quantify regional GABA, glutamate, N-acetylaspartate, and myoinositol concentrations in patients with MS (inclusion criteria: diagnosis of relapsing-remitting [RR] or secondary progressive MS [SPMS]; age 18-80 years) and age and sex-matched healthy controls. Data were collected at a single center between August 2018 and September 2020. Linear mixed-effects models were used to test for associations between metabolite concentrations and cortical lesion volumes within the same MR-spectroscopy voxel. Forty-seven patients with MS (34 RRMS, 13 SPMS; 45.1 ± 12.5 years; 31 women) and 23 healthy controls (44.4 ± 13 years, 15 women) were studied. In patients, higher regional glutamate and lower regional GABA concentrations were associated with larger cortical lesion volume within the MR-spectroscopy voxel [glutamate: 0.61 (95% CI 0.19-1.03) log(mm3), p = 0.005, GABA: -0.71 (-1.24 to -0.18) log(mm3), p = 0.01]. In addition, lower N-acetylaspartate levels [-0.37 (-0.67 to -0.07) log(mm3), p = 0.016] and higher myoinositol levels [0.48 (0.03-0.93) log(mm3), p = 0.037] were associated with a larger regional cortical lesion volume. Furthermore, glutamate concentrations were reduced in patients with SPMS compared with healthy participants [-0.75 (-1.3 to -0.19) mM, p = 0.005] and patients with RRMS [-0.55 (-1.07 to -0.02) mM, p = 0.04]. N-acetylaspartate levels were lower in both patients with RRMS [-0.81 (-1.39 to -0.24) mM, p = 0.003] and SPMS [-1.31 (-2.07 to -0.54) mM, p < 0.001] when compared with healthy controls. Creatine-normalized N-acetylaspartate levels were associated with performance in the 9-hole peg test of the contralateral hand [-0.004 (-0.007 to -0.002) log(s), p = 0.002], and reduced mean creatine-normalized glutamate was associated with increased Expanded Disability Status Scale (R = -0.39, p = 0.02). Cortical lesions are associated with local increases in glutamate and a reduction in GABA concentration within the lesional or perilesional tissue. Further studies are needed to investigate the causal relationship between cortical lesions and changes in neurotransmitter concentrations.

The protective effect of karanjin against sepsis-induced acute lung injury in mice is involved in the suppression of the TLR4 pathway.

Sepsis-induced acute lung injury (ALI) is a severe complication of sepsis. Karanjin, a natural flavonoid compound, has been proved to have anti-inflammatory function, but its role in sepsis-stimulated ALI is uncertain. Herein, the effect of karanjin on sepsis-stimulated ALI was investigated. We built a mouse model of lipopolysaccharide (LPS)-stimulated ALI. The histopathological morphology of lung tissues was scrutinized by hematoxylin-eosin (H&E) staining. The lung injury score and lung wet/dry weight ratio were detected. The myeloperoxidase (MPO) activity and malondialdehyde (MDA) content were scrutinized by commercial kits. Murine alveolar lung epithelial (MLE-12) cells were treated with LPS to mimic a cellular model of ALI. The cell viability was scrutinized by the CCK-8 assay. The contents of proinflammatory cytokines were scrutinized by qRT-PCR and ELISA. The TLR4 and MyD88 contents were scrutinized by qRT-PCR and western blotting. Results showed that karanjin alleviated LPS-stimulated ALI in mice by inhibiting lung tissue lesions, edema, and oxidative stress. Moreover, karanjin inhibited LPS-stimulated inflammation and TLR4 pathway activation in mice. However, treatment with GSK1795091, an agonist of TLR4, attenuated the effects of karanjin on LPS-induced ALI. Furthermore, karanjin repressed LPS-stimulated inflammatory response and TLR4 pathway activation in MLE-12 cells. Overexpression of TLR4 attenuated karanjin effects on LPS-stimulated inflammatory responses in MLE-12 cells. In conclusion, karanjin repressed sepsis-stimulated ALI in mice by suppressing the TLR4 pathway.

Study on the relationship between Methylation of Neuregulin (NRG) Gene and Cervical Carcinoma.

To investigate the relationship between the DNA methylation state of NRG1 promoter and its expression changes, and to analyze the clinical significance of its regulatory mechanism of DNA methylation in cervical carcinoma. This was a retrospective study. One-hundred and twenty patients from the Department of Gynecology of Cangzhou People's Hospital from September 2017 to September 2019 were selected, including 40 cases of cervical SCC, 40 cases of high grade squamous intraepithelial lesions(HSIL) and 40 cases of control cervical tissues. RT-qPCR, immunohistochemistry and DNA methylation-specific PCR(MSP) were used to detect the mRNA and protein expression of NRG1 and DNA methylation status in different tissue types. Immunohistochemical results showed that the positive protein expression rate of NRG1 gene in the SCC group was lower than that in both HSIL and Control groups. RT-qPCR results showed that the mRNA gene of NRG1 gradually decreased in expression with the increase of cervical tissue lesions, with a statistically significant difference. Similarly, it also found that the mRNA expression level of NRG1 in the SCC group was independent of patients' age (p>0.05), but significantly correlated with tumor pathological staging, surgical pathology staging and lymphatic metastasis (p<0.05). Furthermore, methylation-specific PCR results revealed a significantly higher DNA methylation rate of NRG1 gene in the SCC group than in both HSIL and Control groups, with a statistically significant difference. Moreover, the methylation degree of NRG1 gene in SCC tissues was negatively correlated with its mRNA expression (p<0.05). Abnormal DNA hypermethylation of NRG1 gene inhibits the expression of mRNA and protein in the progression of cervical tissue from normal to cancerous state, which is involved in the occurrence and development of cervical carcinoma.

Benign Fibrous Histiocytoma of Gingiva: A Rare Case Report

Abstract Fibrous histiocytoma is a benign soft-tissue neoplasm that commonly involves the dermis. It is rare in the oral cavity. This lesion creates a diagnostic dilemma due to its nonspecific clinical appearance and microscopic similarities with other benign fibrous tissue lesions. Microscopically, it shows the proliferation of both spindle-shaped fibroblasts and histiocytes. Surgical excision is the treatment of choice with a good prognosis. The purpose of this paper is to report a rare case of gingival benign fibrous histiocytoma occurring in an 11-year-old female patient. The diagnosis of this lesion is based on combined clinical, histopathological, and immunohistochemical features.

Performance Comparison of Augmented Reality Versus Ultrasound Guidance for Puncture: A Phantom Study.

Augmented reality (AR) is an innovative approach that could assist percutaneous procedures; by directly seeing "through" a phantom, targeting a lesion might be more intuitive than using ultrasound (US). The objective of this study was to compare the performance of experienced interventional radiologists and operators untrained in soft tissue lesion puncture using AR guidance and standard US guidance. Three trained interventional radiologists with 5-10years of experience and three untrained operators performed punctures of five targets in an abdominal phantom, with US guidance and AR guidance. Correct targeting, accuracy (defined as the Euclidean distance between the tip and the center of the target), planning time, and puncture time were documented. Accuracy was higher for the trained group than the untrained group using US guidance (1mm versus 4mm, p = 0.001), but not when using AR guidance (4mm vs. 4mm, p = 0.76). All operators combined, no significant difference was found concerning accuracy between US and AR guidance (2mm vs. 4mm, p = 0.09), but planning time and puncture time were significantly shorter using AR (respectively, 15.1s vs. 74s, p < 0.001; 16.1s vs. 59s; p < 0.001). Untrained and trained operators obtained comparable accuracy in percutaneous punctures when using AR guidance whereas US performance was better in the experienced group. All operators together, accuracy was similar between US and AR guidance, but shorter planning time, puncture time were found for AR guidance.

The Patient Acceptable Symptom State (PASS) after proximal and distal femoral replacement

IntroductionFemoral megaprostheses are used for bone reconstruction surgery in patients with local tumors or who require multiple revisions. Patient reported outcome measures (PROMs) provide a subjective result and, like patient satisfaction, have become an integral part of the outcomes in orthopedics. However, the threshold of satisfaction (PASS: Patient Acceptable Symptom State) has not yet been defined in a French population after this type of arthroplasty. This led us to carry out a retrospective study on a population of patients who received a femoral reconstruction megaprosthesis in order to 1) define the PASS for the Harris Hip Score (HHS), Knee Society Score (KSS) and the Musculoskeletal Tumor Society score (MSTS), 2) study the complications. HypothesisThe PASS threshold for proximal femur and distal femur reconstruction prothesis for the HHS and the KSS, respectively, will be lower than the threshold for these same scores for primary arthroplasty. Materials and methodsForty-four patients who were operated on between 2009 and 2020 were included: 23 received a proximal femur prosthesis and 21 received a distal femur prosthesis. The PASS threshold was defined using an anchoring strategy by analyzing ROC curves for the HSS for the proximal femur, KSS for the distal femur and the MSTS for all the prostheses. Complications were classified according to Henderson. ResultsThe mean follow-up was 4.5 ± 3.6 (1–12.5) years. The PASS threshold was 47.5 (area under curve (AUC) 0.71 (0.45–0.97)) for the HHS, 69.5 (AUC 0.97 (0.92–1.0)) for the KSS knee and 62.5 (AUC 0.81 (0.61–0.99)) for the KSS function. Thirteen patients (29%) had complications, nine of whom required another surgery (20%). The most frequent were Henderson type 1 (soft tissue lesions, n = 5/44 [11%]) and type 2 (loosening, n = 5/44 [11%]) There was no relationship between satisfaction and postoperative complications (p = 0.071). DiscussionMost of the patients who undergo femoral resection and reconstruction (59%) are satisfied with their function, albeit reduced, despite a high complication rate (29%). Our hypothesis is confirmed for the PASS threshold for the HHS (47.5 versus 93) and the KSS knee and function (69.5 and 62.5 versus 85.5 and 72.5). Level of evidenceIV; retrospective observational single-center study.

Innate immune training restores pro-reparative myeloid functions to promote remyelination in the aged central nervous system

The reduced ability of the central nervous system to regenerate with increasing age limits functional recovery following demyelinating injury. Previous work has shown that myelin debris can overwhelm the metabolic capacity of microglia, thereby impeding tissue regeneration in aging, but the underlying mechanisms are unknown. In a model of demyelination, we found that a substantial number of genes that were not effectively activated in aged myeloid cells displayed epigenetic modifications associated with restricted chromatin accessibility. Ablation of two class I histone deacetylases in microglia was sufficient to restore the capacity of aged mice to remyelinate lesioned tissue. We used Bacillus Calmette-Guerin (BCG), a live-attenuated vaccine, to train the innate immune system and detected epigenetic reprogramming of brain-resident myeloid cells and functional restoration of myelin debris clearance and lesion recovery. Our results provide insight into aging-associated decline in myeloid function and how this decay can be prevented by innate immune reprogramming.

Histological Findings of Osteomyelitis in Patients with Diabetic Foot and Their Correlation with Radiologic Findings

Objective: Osteomyelitis in patients with diabetic foot has been diagnosed clinically, radiologically, and histologically. However, the accuracy of these diagnostic modalities is not well established. In this study, we histologically reviewed patients who underwent surgical procedures for diabetic foot osteomyelitis and correlated these histological features with radiological findings.Methods: Eighty patients who were clinically diagnosed with diabetic foot osteomyelitis, who underwent surgical treatment between November 2017 and February 2022, were enrolled. Hematoxylin and eosin-stained slides and radiological findings were reviewed.Results: Eighty patients were radiologically examined by magnetic resonance imaging (MRI) (49 cases) and/or 99mTc-hexamethyl-propylene amine oxime-labeled white blood cells single-photon emission computed tomography (SPECT)/computed tomography (CT) (65 cases). MRI findings were suggestive of osteomyelitis in 35 cases (71.4%) and soft tissue inflammation in 46 cases (93.8%). In SPECE/CT, 60 cases (92.3%) and 64 cases (98.4%) showed signs of osteomyelitis and soft tissue inflammation, respectively. Histologically, both bone and soft tissue lesions were found in 32 cases (40%), only bone tissue lesions in seven cases (8.8%), and only soft tissue lesions in 40 cases (50%). The sensitivity and specificity of MRI for osteomyelitis were 83.3% (10/12) and 28.6% (4/14), and that of SPECT/CT was 100.0% (12/12) and 12.5% (2/16), respectively. Moreover, those of by MRI findings for soft tissue inflammation were 90.6% (29/32) and 0% (0/12), while that of SPECT/CT was 97.4% (38/39) and 0% (0/18), respectively.Conclusion: For accurate histological diagnosis of diabetic foot osteomyelitis, sufficient specimens should be obtained. White blood cell SPECT/CT seems to be a more sensitive modality than MRI for the detection of osteomyelitis.

Comprehensive insights into Menkes disease: Genetics, pathophysiology, animal models, diagnosis, and therapeutic strategies

Menkes disease (MD) is an inherited disorder affecting primarily the males which is X-linked recessive in inheritance pattern due to mutation in ATP7A gene that codes for copper transporter protein. This results in neurological complications and connective tissue lesions that make affected males succumb to death. MD can be classified as the classical and Occipital Horn Syndrome (OHS) varieties, though the severity and early presentation of the classical MD is more pronounced. Diagnostic assays include determination of serum copper and ceruloplasmin concentrations; neurochemical studies are also performed. The standard treatment usually entails the use of copper supplements with copper – Histidine being one of the most effective. Therefore, it is necessary to investigate the molecular pathophysiology of ATP7A disorder to come up with different therapies. Animal models such as zebrafish, fruit flies etc. are beneficial to know about MD pathology to get treatment. In summary, the early and accurate diagnosis of MD, followed by immediate treatment, plays a critical role in successful management of the disorder.

Deciphering the pathogenesis of melanized focal changes in the white skeletal muscle of farmed Atlantic salmon (Salmo salar).

Melanized focal changes (MFCs) in the fillet of farmed Atlantic salmon is a major quality concern. The changes are thought to initially appear as acute red focal changes (RFCs) that progress into chronic MFCs. Recent findings have indicated that hypoxia may be important in their development, possibly leading to necrosis affecting not only myocytes but also adipocytes. Thus, the aim of this study was to investigate possible hypoxic conditions in RFCs and the subsequent inflammatory responses and lesions in the adipose tissue in RFCs and MFCs. A collection of RFCs, MFCs and control muscle samples from several groups of farmed salmon was studied. Using immunohistochemistry, we found induction of the hypoxia-inducible factor 1 pathway in RFCs. Histological investigations of RFCs and MFCs revealed different stages of fat necrosis, including necrotic adipocytes, a myospherulosis-like reaction and the formation of pseudocystic spaces. Accumulations of foamy macrophages were detected in MFCs, indicating degradation and phagocytosis of lipids. Using insitu hybridization, we showed the presence of tyrosinase- and tyrosinase-related protein-1-expressing amelanotic cells in RFCs, which in turn became melanized in MFCs. In conclusion, we propose a sequence of events leading to the formation of MFCs, highlighting the pivotal role of adiposity, hypoxia and fat necrosis.

Clinical characteristic, management, and outcomes of cervical spinal brucellosis: a retrospective cohort study over 1-year postoperative follow-up

BackgroundThe incidence of cervical spinal brucellosis is low, only a few case reports have been published, and case series are not widely reported in the medical literature. Therefore, clinical features, management, and outcomes of cervical spinal brucellosis are relatively unknown. In this series, the authors report 15 cases of patients with cervical spinal brucellosis, including clinical characteristic, imaging findings, management plans, the institution’s experience, and outcomes at 1 year postoperatively.MethodsThe study reviewed the clinical and radiographic records of 15 patients who received antimicrobial pharmacotherapy, and anterior cervical debridement and fusion for cervical spinal brucellosis. The data collected included patient demographic characteristics, spinal level affected, abscess, neurology, pathological reports, duration and type of antimicrobial regimens, details of orthopedic management, and complications incurred during the procedure.ResultsNeck pain (100%) and limb paralysis (86.7%) were the most common clinical presentations, and the disease had a rapid progression. The C6-7 segment was the most commonly affected segment, followed by C4-5 and C5-6. Imaging commonly revealed epidural or paravertebral abscesses (80%). There was a significant improvement in the VAS, JOA, and NDI scores three months after surgery, and the scores continued to improve until the final follow-up. There was a statistically significant difference between the pre- and postoperative scores (P < 0.05). The ESR and CRP levels returned to normal within three months postoperatively, being 7.7 ± 4.5 mm/h and 7.55 ± 3.48 mg/L, respectively. There were statistically significant differences between the pre- and postoperative levels (P < 0.05). The positive rate of bacterial culture testing of pus or lesion tissues was only 40%, but blood cultures revealed an even lower positivity rate (33.3%). The average antimicrobial pharmacotherapy regimen duration was 6.1 ± 1.9 months. All patients achieved intervertebral bone fusion within 8 months (4.8 ± 1.4 months) after surgery and were cured with non-recurrence.ConclusionsSpinal brucellosis rarely affects the cervical region, but its impact is more dangerous due to potential complications such as paraplegia or tetraplegia arising from epidural abscesses that compress the spinal cord. Surgical debridement, along with essential antimicrobial therapy, is an effective strategy and can lead to satisfactory prognosis in managing cervical spinal brucellosis.