Local eosinophils are associated with increased IgA subclass levels in the sinonasal mucosa of chronic rhinosinusitis with polyp patients

Background: Chronic rhinosinusitis (CRS) describes an inflammatory condition affecting the sinonasal mucosa. As the immune system players such as immunoglobulins play prominent roles in the development of CRS, we aimed to investigate the expression of IgA subclasses and factors involved in IgA class switching in the sinonasal mucosa of CRS patients. Methods: Specimens were collected from the sinonasal mucosa of the healthy controls and CRS patients. Histological assessments were performed by H&E and immunohistochemistry. Real-time PCR and ELISA methods were applied to measure gene expression and protein levels extracted from tissue samples, respectively. Results: We observed that total IgA and subclass-positive cells were higher in the patient groups than controls. There was a significant correlation between the number of eosinophils and total IgA and subclasses-positive cells (Pv < 0.0001). The expression of CXCL13, BAFF, AID, and germline transcripts were increased in CRSwNP patients. In contrast to IgA2 levels, IgA1 levels were significantly increased in the sinonasal tissue of CRSwNP patients (Pv < 0.01). TGF-β was significantly elevated in the sinonasal tissue of patients with CRSsNP. Conclusions: Increased protein levels of IgA subclasses and related antibody-producing cells were associated with elevated eosinophils in CRSwNP patients which may result in eosinophil pathological functions. Several therapeutic approaches might be developed to modulate the IgA production to ameliorate the inflammatory mechanisms in CRSwNP patients.Figure not available: see fulltext. © 2020 The Author(s)

Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis.

Generalized lymphatic dysplasia (GLD) is a rare form of primary lymphoedema characterized by a uniform, widespread lymphoedema affecting all segments of the body, with systemic involvement such as intestinal and/or pulmonary lymphangiectasia, pleural effusions, chylothoraces and/or pericardial effusions. This may present prenatally as non-immune hydrops. Here we report homozygous and compound heterozygous mutations in PIEZO1, resulting in an autosomal recessive form of GLD with a high incidence of non-immune hydrops fetalis and childhood onset of facial and four limb lymphoedema. Mutations in PIEZO1, which encodes a mechanically activated ion channel, have been reported with autosomal dominant dehydrated hereditary stomatocytosis and non-immune hydrops of unknown aetiology. Besides its role in red blood cells, our findings indicate that PIEZO1 is also involved in the development of lymphatic structures

Early effects of parathyroid hormone on bisphosphonate/steroid-associated compromised osseous wound healing

Summary: Administration of intermittent parathyroid hormone (PTH) promoted healing of tibial osseous defects and tooth extraction wounds and prevented the development of necrotic lesions in rats on a combined bisphosphonate and steroid regimen. Introduction: Osteonecrosis of the jaw (ONJ) has emerged in association with antiresorptive therapies. The pathophysiology of ONJ is unknown and no established cure currently exists. Our objective was to determine the effect of intermittent PTH administration on early osseous healing in the jaw and long bones of rats receiving bisphosphonate and steroid treatment. Methods: Ovariectomized rats received the combination therapy of alendronate and dexamethasone (ALN/DEX) for 12 weeks. Osseous wounds were created in the jaw and tibia. PTH was administered intermittently and healing at 2 weeks post-op was compared between the jaw and tibia by microcomputed tomography and histomorphometric analyses. Results: ALN/DEX treatment was associated with necrotic open wounds in the jaw but had no negative effects on healing and promoted bone fill in tibial defects. PTH therapy prevented the development of necrotic lesions in the jaw and promoted healing of the tibial defects. PTH therapy was associated with the promotion of osteocyte survival in osseous wounds both in the jaw and tibia. Conclusions: Wound healing was impaired in the jaw in rats on a combined bisphosphonate and steroid regimen, and PTH therapy rescued necrotic lesions. These findings suggest that PTH therapy could be utilized to prevent ONJ from occurring in patients on combination antiresorptive and steroid therapy

Early Damage Detection for Partially Observed Structures with an Autoregressive Spectrum and Distance-Based Methodology

Vibration-based Structural Health Monitoring (SHM) methods often rely upon vibration responses measured with a pervasive network of sensors. In some cases, it does not look possible for technical and economic reasons to equip civil structures with a distributed sensing system. Hence, the amount of information to handle for damage detection may be seriously affected by environmental and/or operational variability, leading to false detection results. To address this challenge, we present a parametric spectral method based on AutoRegressive (AR) modeling to set the damage-sensitive structural features. The spectra of the AR models associated with the normal and damaged conditions are collected into two matrices, to provide individual multivariate feature datasets in the frequency domain. By vectorising the matrices, two series of feature samples relevant to the normal and damaged conditions are obtained. To detect damage, the Logspectral distance method is adopted to measure the similarity between the two aforementioned feature vectors. The effectiveness and accuracy of the proposed approach are assessed through limited vibration data relevant to the IASC-ASCE benchmark problem. Results show that the AR spectrum stands as a reliable and sensitive feature for partially observed structures, hence in the case of limited sensor locations; additionally, the presented distance methodology succeeds in detecting early damage

Protoplasmic astrocytoma with multifocal involvement: case report and radiological findings

Protoplasmic astrocytomas are a poorly characterized and extremely rare subtype of astrocytoma. We describe the CT, MR and 18F-fludeoxyglucose positron emission tomography (FDG-PET) findings of a multifocal protoplasmic astrocytoma in a 29-year-old male with neurological deficits. He was initially diagnosed with neurosarcoidosis based on imaging. MRI demonstrated intraparenchymal lesions involving the right temporal lobe and cerebellum. These appeared as extremely hyperintense signals on T2 weighted imaging and as homogeneous enhancements with a small non-enhancing cystic component on contrast-enhanced MR. Diffuse post-contrast enhancement of the craniospinal meninges was also noted. Post-radiation therapy PET-CT demonstrated a highly FDG-avid tumour in the right temporal lobe and left cerebellum. To our knowledge, a multifocal form of protoplasmic astrocytoma in an adult patient has not been previously described

Direct and indirect effects of exposure to 900 MHz GSM radiofrequency electromagnetic fields on CHO cell line: Evidence of bystander effect by non-ionizing radiation

© 2019 Introduction: The rapid rise in global concerns about the adverse health effects of exposure to radiofrequency radiation (RFR)generated by common devices such as mobile phones has prompted scientists to further investigate the biological effects of these environmental exposures. Non-targeted effects (NTEs)are responses which do not need a direct exposure to be expressed and are particularly significant at low energy radiations. Although NTEs of ionizing radiation are well documented, there are scarcely any studies on non-targeted responses such as bystander effect (BE)after exposure to non-ionizing radiation. The main goal of this research is to study possible RFR-induced BE. Material and methods: Chinese hamster ovary cells were exposed to 900 MHz GSM RFR at an average specific absorption rate (SAR)of 2 W/kg for 4, 12 and 24 hours (h). To generate a uniformly distributed electromagnetic field and avoid extraneous RF exposures a cavity was desined and used. Cell membrane permeability, cell redox activity, metabolic and mitotic cell death and DNA damages were analyzed. Then the most effective exposure durations and statistically significant altered parameters were chosen to assess the induction of BE through medium transfer procedure. Furthermore, intra and extra cellular reactive oxygen species (ROS)levels were measured to assess the molecular mechanism of BE induced by non-ionizing radiation. Results: No statistically significant alteration was found in cell membrane permeability, cell redox activity, metabolic cell activity and micronuclei (MN)frequency in the cells directly exposed to RFR for 4, 12, or 24 h. However, RFR exposure for 24 h caused a statistically significant decrease in clonogenic ability as well as a statistically significant increase in olive moment in both directly exposed and bystander cells which received media from RFR-exposed cells (conditioned culture medium; CCM). Exposure to RFR also statistically significant elevated both intra and extra cellular levels of ROS. Conclusion: Our observation clearly indicated the induction of BE in cells treated with CCM. To our knowledge, this is the first report that a non-ionizing radiation (900 MHz GSM RFR)can induce bystander effect. As reported for ionizing radiation, our results proposed that ROS can be a potential molecule in indirect effect of RFR. On the other hand, we found the importance of ROS in direct effect of RFR but in different ways