N-methyl-D-aspartate (NMDA) receptor-evoked excitotoxicity contributes to region-specific loss of glutamatergic synapses responsible for cognitive decline in Alzheimer's disease (AD). Here, the post-synaptic scaffold proteins PSD-95 and SAP-102, which regulate NMDA receptor synaptic activity and expression, were investigated in human AD autopsy brain tissue. Using absolute quantification real-time PCR, we detected reduced expression of synaptophysin in both the pathologically susceptible inferior temporal cortex and hippocampus, consistent with previous reports. PSD-95 and SAP-102 mRNA was reduced, albeit not significantly. Proteins were precisely quantified against recombinant truncated protein standards. No differences were observed for proteins in AD spared occipital cortex between AD cases and controls. PSD-95 and SAP-102 protein expression was markedly reduced in the AD inferior temporal cortex. Both mRNA and protein levels were reduced according to disease severity. SAP102 protein levels were significantly reduced in AD subjects carrying a copy of the APOEε4 allele. This is the first study to investigate SAP-102 in the aging human brain and suggest a possible mechanism for NMDA receptor expression aberrations in AD.
Background Meningioma, a most common brain tumor, has a high rate of recurrence. Tumor-associated macrophages (TAMs) are the most abundant immune cell type in meningioma. TAMs display functional phenotypic diversity and may establish either an inflammatory and anti-tumoral or an immunosuppressive and pro-tumoral microenvironment. TAM subtypes present in meningioma and potential contribution to growth and recurrence is unknown. Methods Immunofluorescence staining was used to quantify M1 and M2 TAM populations in tissues obtained from 30 meningioma patients. Associations between M1 and M2 cells, M1:M2 cell ratio to tumor characteristics, WHO grade, recurrence, size, location, peri-tumoral edema, and patient demographics such as age and sex were examined. Results TAM cells accounted for ~18% of all cells in meningioma tissues. More than 80% of infiltrating TAMs were found to be of pro-tumoral M2 phenotype and correlated to tumor size (P = .0409). M1:M2 cell ratio was significantly decreased in WHO grade II, compared to grade I tumors (P = .009). Furthermore, a 2.3-fold difference in M1:M2 ratio between primary (0.14) and recurrent (0.06) tumors was observed (n = 18 and 12 respectively, P = .044). Conclusion This study is the first to confirm existence of pro-tumoral M2 TAMs in the meningioma microenvironment, emphasizing its potential role in tumor growth and recurrence.
SARS-CoV-2 antigen tests used at the point-of-care, such as the Abbott Panbio, have great potential to help combat the COVID-19 pandemic. The Panbio is Health Canada approved for the detection of SARS-CoV-2 in symptomatic individuals within the first 7 days of COVID-19 symptom onset(s). Symptomatic adults recently diagnosed with COVID-19 in the community were recruited into the study. Paired nasopharyngeal (NP), throat, and saliva swabs were collected, with one paired swab tested immediately with the Panbio, and the other transported in universal transport media and tested using real-time reverse-transcriptase polymerase chain reaction (RT-PCR). We also prospectively evaluated results from assessment centers within the community. For those individuals, an NP swab was collected for Panbio testing and paired with RT-PCR results from parallel NP or throat swabs. One hundred and forty-five individuals were included in the study. Collection of throat and saliva was stopped early due to poorer performance (throat sensitivity 57.7%, n=61, and saliva sensitivity 2.6%, n=41). NP swab sensitivity was 87.7% [n=145, 95% confidence interval (CI) 81.0-92.7%]. There were 1641 symptomatic individuals tested by Panbio in assessment centers with 268/1641 (16.3%) positive for SARS-CoV-2. There were 37 false negatives and 2 false positives, corresponding to a sensitivity and specificity of 86.1% [95% CI 81.3-90.0%] and 99.9% [95% CI 99.5-100.0%], respectively. The Panbio test reliably detects most cases of SARS-CoV-2 from adults in the community setting presenting within 7 days of symptom onset using nasopharyngeal swabs. Throat and saliva swabs are not reliable specimens for the Panbio.
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