Background: Tau is secreted unconventionally, possibly explaining increased CSF phosphotau levels in early AD. Results: M1C cells secrete selectively phosphorylated, exosomal tau. These characteristics in early AD CSF tau suggest that CSF tau is secreted, not shed from dead neurons. Conclusion: Tau secretion occurs early and may explain lesion spreading in AD. Significance: Secretion biomarkers may become revolutionary prospective AD diagnostics.
IMPORTANCE Potentially harmful chemicals are released when tissues are vaporized. Laser hair removal (LHR) causes heating and often vaporization of hairs, producing both a signature malodorous plume and visible particulates.OBJECTIVE To characterize the chemical composition and quantify the ultrafine particle content of the plume generated during LHR. DESIGN, SETTING, AND PARTICIPANTSIn the laser center of a large academic hospital, discarded terminal hairs from the trunk and extremities were collected from 2 adult volunteers. The hair samples were sealed in glass gas chromatography chambers and treated with a laser. The laser plume was analyzed by gas chromatography-mass spectrometry (GC-MS). During LHR treatment, two 6-L negative pressure canisters were used to capture 30 seconds of laser plume, and a portable condensation particle counter was used to measure ultrafine particulates (<1 μm). Ultrafine particle concentrations were measured within the treatment room, within the waiting room, and outside the building. MAIN OUTCOMES AND MEASURESThe chemical content of the laser plume was analyzed with GC-MS and screened for aerosolized toxins using Environmental Protection Agency-certified methods. The ambient concentration of ultrafine particles during LHR was measured by condensation particle counters.RESULTS Analysis with GC-MS identified 377 chemical compounds. Sixty-two of these compounds, of which 13 are known or suspected carcinogens and more than 20 are known environmental toxins, exhibited strong absorption peaks. During LHR, the portable condensation particle counters documented an 8-fold increase compared with the ambient room baseline level of ultrafine particle concentrations (ambient room baseline, 15 300 particles per cubic centimeter [ppc]; LHR with smoke evacuator, 129 376 ppc), even when a smoke evacuator was in close proximity (5.0 cm) to the procedure site. When the smoke evacuator was turned off for 30 seconds, there was a more than 26-fold increase in particulate count compared with ambient baseline levels (ambient baseline, 15 300 ppc; LHR without smoke evacuator for 30 seconds, 435 888 ppc). CONCLUSIONS AND RELEVANCEThese findings establish the concern that the burning-hair plume often present during LHR should be considered a biohazard, warranting the use of smoke evacuators, good ventilation, and respiratory protection, especially for health care workers with prolonged exposure to LHR plume.
Tau misprocessing to form aggregates and other toxic species has emerged as a major feature in our developing understanding of the etiology and pathogenesis of Alzheimer's Disease (AD). The significance of tau misprocessing in AD has been further emphasized by recent studies showing that tau can be secreted from neurons via exosomes and may itself be an important agent in the spreading of neurofibrillary lesions within the brain. Tau secretion occurs most readily under disease-associated conditions in cellular models, suggesting that cellular changes responsible for secretion, possibly including tau oligomerization, could play a key role in the propagation of neurofibrillary lesions in neurodegenerative disease. Here we show that overexpression of 4R0N human tau in neuroblastoma cells recruits mitochondrial and axonogenesis-associated proteins relevant to neurodegeneration into the exosomal secretion pathway via distinct mechanisms. The recruitment of mitochondrial proteins appears to be linked to autophagy disruption (exophagy) in multiple neurodegenerative conditions but but has few known direct links to AD and tau. By contrast, the involvement of synaptic plasticity and axonogenesis markers is highly specific to both tau and AD and may be relevant to the reactivation of developmental programs involving tau in AD and the recently demonstrated ability of secreted tau to establish tissue distribution gradients in CNS neuropil. We also found a highly significant correlation between genes that are significantly downregulated in multiple forms of AD and proteins that have been recruited to exosomes by tau, which we interpret as strong evidence for the central involvement of tau secretion in AD cytopathogenesis. Our results suggest that multiple cellular mechanisms may link tau secretion to both toxicity and and neurofibrillary lesion spreading in Alzheimer's disease and other tauopathies.
(Abstracted from Cell 2020;181:1680–1692) Pregnancy is a vital time period for both mothers and fetuses, and obstetric care can greatly increase positive outcomes of mothers and children. Accurate prediction of gestational age is one of the many important components of care during pregnancy.
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