Chronic rhinosinusitis with nasal polyposis (CRSwNP): the correlation between expression of Galectin-10 and Clinical-Cytological Grading (CCG)

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is typically characterized by Type 2 inflammation. Several biomarkers of eosinophilic inflammation, including Galectin-10, also known as Charcot-Leyden crystal protein (CLCP), have been identified to establish eosinophilic infiltration of polyps, a reliable predictor of recurrence. Objective: We aimed to evaluate the Galectin-10 expression in nasal polyps of patients with CRSwNP and to assess the correlation of Charcot-Leyden crystals expression to the severity of CRSwNP according to Clinical-Cytological Grading (CCG). Methods A double-label immunofluorescence was performed to evaluate the expression of Gal-10, CD15, Tryptase, and CD63 and their eventual co-localization on histological samples of 18 patients with CRSwNP. Double-positive Gal-10+CD15+ and Galectin-10+Tryptase+ inflammatory cells were counted by confocal microscopy. Results Galectin-10 was detectable in all examined tissues from CRSwNP patients, and its expression increased as low, medium and high CCG tissues were examined, respectively. Galectin-10 was extensively present in inflammatory cells, while limited Galectin-10 deposits were detected around mucosal epithelial cells. Conclusion We showed the strong correlation between CCG and Galectin-10 expression, mainly colocalized with infiltrating eosinophils and mast-cells, in patients affected by CRSwNP.

Prefrontal cortex neural compensation during an operant devaluation task

Deficits in goal-directed action are reported in multiple neuropsychiatric conditions, including schizophrenia. However, dysfunction is not always apparent in early stages of schizophrenia, possibly due to neural compensation. We designed a novel devaluation task in which goal-directed action could be guided by stimulus-outcome (S-O) [presumably orbitofrontal cortex (OFC)-mediated] or response-outcome (R-O) associations [presumably prelimbic cortex (PL)-mediated]. We previously found suggestive evidence that OFC and PL could compensate for each other in this task, and we more directly assessed this potential compensation here. In Experiment 1, rats received OFC, PL, combined OFC+PL, or sham lesions and then completed our devaluation task. The OFC+PL lesion group exhibited impaired devaluation. In Experiment 2, rats received cholera-toxin-b (CTb) into OFC and either neurotoxic or sham PL lesions. Rats were then sacrificed on the last training day to double-label for Arc and CTb. We found increased Arc+CTb in mediodorsal thalamus (MD) and increased Arc+ neurons in OFC when PL was lesioned, suggesting that PL lesions lead to a compensatory increased activation of the MD->OFC circuit. Our results suggest that our devaluation task can model neural compensation between OFC and PL and this compensation may be regulated by MD.

Microglial response to experimental periodontitis in a murine model of Alzheimer’s disease

Periodontal disease (PD) has been suggested to be a risk factor for Alzheimer’s disease (AD). We tested the impact of ligature-induced PD on 5xFAD mice and WT littermates. At baseline, 5xFAD mice presented significant alveolar bone loss compared to WT mice. After the induction of PD, both WT and 5xFAD mice experienced alveolar bone loss. PD increased the level of Iba1-immunostained microglia in WT mice. In 5xFAD mice, PD increased the level of insoluble Aβ42. The increased level in Iba1 immunostaining that parallels the accumulation of Aβ in 5xFAD mice was not affected by PD except for a decrease in the dentate gyrus. Analysis of double-label fluorescent images showed a decline in Iba1 in the proximity of Aβ plaques in 5xFAD mice with PD compared to those without PD suggesting a PD-induced decrease in plaque-associated microglia (PAM). PD reduced IL-6, MCP-1, GM-CSF, and IFN-γ in brains of WT mice and reduced IL-10 in 5xFAD mice. The data demonstrated that PD increases neuroinflammation in WT mice and disrupts the neuroinflammatory response in 5xFAD mice and suggest that microglia is central to the association between PD and AD.

Research on Automated Warehouse Scheduling System Based on Double Label and Sorting Algorithm

Through the research on the RFID’s User tag memory and its coding mode, a double-label management mode based on the combination of RFID tag and barcode is proposed, which realizes the binding of information in the warehouse logistics process, the convenient transmission and traceability between the upstream and downstream departments. The interface between the scheduling system and the equipment control system is designed, and the scheduling algorithm based on priority ranking is put forward to realize material outbound in order in warehouse logistics system. This method is an extension of the warehouse and logistics information system, which can solve the problem of the accuracy of the material outbound in sequence to the downstream departments.

Microvascular pathology of Friedreich cardiomyopathy

Nikolaus Friedreich (1877) was aware of heart disease in his patients but thought it was unrelated to the neurological disorder. In 1946, Dorothy Russell considered cardiomyopathy an integral part of Friedreich ataxia (FA). In addition to sparse inflammatory infiltration, sections show fibrosis and capillary hyperplasia. We examined the left ventricular walls of 41 homozygous FA patients aged 10–87 and 21 controls aged 2–69. An antibody to CD34 enabled quantitative capillary profile counts for a comparison with cardiomyocyte counts in the same field. Mean capillary counts in normals were 1926±341/mm2, and the median ratio of capillaries to cardiomyocytes was 1.0 (interquartile range [IQR]: 0.9-1.2). In FA, however, the number of cardiomyocytes/mm2 was less, and the median ratio of capillaries to heart fibers was 2.0 (IQR 1.4-2.4). There was a significant correlation of the higher guanine-adenine-adenine trinucleotide length (shorter allele, GAA1) with the younger age of onset, shorter disease duration, and lower cardiomyocyte counts. The ratio of capillaries to heart fibers was higher in patients with long GAA1 repeat expansions (e.g., 3.31 in GAA1 of 1200). Double-label immunofluorescence for CD34 and S100A4 revealed co-expression in endothelial cells, supporting endothelial-to-mesenchymal transition in the pathogenesis of cardiac fibrosis (supported by Friedreich’s Ataxia Research Alliance).LEARNING OBJECTIVESThe presentation will enable the learner to:1.Describe endothelial-to-mesenchymal transition in the pathogenesis of cardiac fibrosis in Friedreich cardiomyopathy