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Reactive astrocytes and dystrophic neurites, most aberrant presynaptic elements, are found surrounding amyloid-β plaques in Alzheimer's disease (AD). We have previously shown that reactive astrocytes enwrap, phagocytose, and degrade dystrophic synapses in the hippocampus of APP mice and AD patients, but affecting less than 7% of dystrophic neurites, suggesting reduced phagocytic capacity of astrocytes in AD. Here, we aimed to gain insight into the underlying mechanisms by analyzing the capacity of primary astrocyte cultures to phagocytose and degrade isolated synapses (synaptoneurosomes, SNs) from APP (containing dystrophic synapses and amyloid-β peptides), Tau (containing AT8- and AT100-positive phosphorylated Tau) and WT (controls) mice. Trichostatin A We found highly reduced phagocytic and degradative capacity of SNs-APP, but not AT8/AT100-positive SNs-Tau, as compared with SNs-WT. The reduced astrocyte phagocytic capacity was verified in hippocampus from 12-month-old APP mice, since only 1.60 ± 3.81% of peri-plaque astrocytes presented phagocytic structures. This low phagocytic capacity did not depend on microglia-mediated astrocyte reactivity, because removal of microglia from the primary astrocyte cultures abrogated the expression of microglia-dependent genes in astrocytes, but did not affect the phagocytic impairment induced by oligomeric amyloid-β alone. Taken together, our data suggest that amyloid-β, but not hyperphosphorylated Tau, directly impairs the capacity of astrocytes to clear the pathological accumulation of oligomeric amyloid-β, as well as of peri-plaque dystrophic synapses containing amyloid-β, perhaps by reducing the expression of phagocytosis receptors such as Mertk and Megf10, thus increasing neuronal damage in AD. Therefore, the potentiation or recovery of astrocytic phagocytosis may be a novel therapeutic avenue in AD.
To investigate the effects of various types of Dead Sea mud (DSM) on skin barrier properties over a period of four weeks.
The effects of a 4-week application of three types of DSM (as is mud, mud with extra Dead Sea salt, and over the shelf mud) on the barrier properties of normal skin were investigated. Preparations were applied onto forearms of healthy volunteers every other day for 4weeks, and skin hydration, transepidermal water loss (TEWL), melanin, erythema level, skin pH, skin elasticity, dermal thickness, and collagen content were measured at predefined circular areas on subjects' forearms at baseline, week 1, week 2, and week 4 during the treatment phase and on week 5 following a 1-week regression period in which no mud was applied.
The use of DSM for 4 weeks was well tolerated with no noticeable changes in TEWL, skin pH, melanin, and erythema levels. A slight firming effect was observed in the forearms treated with salted DSM. Skin hydration was not significantly affected by any type of DSM. However, a slight drying effect of "as is" and "salted" DSM and slight hydration effect of "over the shelf" DSM were observed. This effect could be attributed to the content of DSM rather than to disruption of skin integrity as confirmed by TEWL values.
Long-term use of all types of DSM did not compromise the barrier integrity of the skin. This provides dermatologists with needed information on safety of DSM and lack of skin disruption activity upon long-term use.
Long-term use of all types of DSM did not compromise the barrier integrity of the skin. This provides dermatologists with needed information on safety of DSM and lack of skin disruption activity upon long-term use.
Dual energy radiography (DER) makes it possible to obtain separate images for soft-tissue and bony structures (tissue maps) based on the acquisition of two radiographs at different source peak-kilovoltage values. Current DER studies are based on the weighted subtraction method, which requires either manual tuning or the use of precomputed tables, or on decomposition methods, which make use of a calibration to model soft-tissue and bone components. In this study, we examined in depth the optimum method to perform this calibration.
We used simulations to optimize the calibration protocol and evaluated the effect of the material and size of a calibration phantom composed of two wedges and its positioning in the system. Evaluated materials were water, PMMA and A-150 as soft-tissue equivalent, and Teflon, B-100 and aluminum as bone equivalent, with sizes from 5 to 30cm. Each material combination was compared with an ideal phantom composed of soft tissue and bone. Our simulation results enabled us to propose four designs that were tested with the NOVA FA X-ray system with a realistic thorax phantom.
Calibration based on a very simple and inexpensive phantom with no strict requirements in its placement results in appropriate separation of the spine (a common focus in densitometry studies) and the identification of nodules as small as 6mm, which have been reported to have a low rate of detection in radiography.
The proposed method is completely automatic, avoiding the need for a radiology technician with expert knowledge of the protocol, as is the case in densitometry exams. The method provides real mass thickness values, enabling quantitative planar studies instead of relative comparisons.
The proposed method is completely automatic, avoiding the need for a radiology technician with expert knowledge of the protocol, as is the case in densitometry exams. The method provides real mass thickness values, enabling quantitative planar studies instead of relative comparisons.Sexual function is a vital aspect of quality of life among adolescent and young adult (AYA) (ages 15-39 years) cancer survivors. Sexual function encompasses physical, psychosocial, and developmental factors that contribute to sexual health, all of which may be negatively impacted by cancer and treatment. However, limited information is available to inform the care of AYA cancer survivors in this regard. This scoping review, conducted by the Children's Oncology Group AYA Oncology Discipline Committee, summarizes available literature regarding sexual function among AYA cancer survivors, including relevant psychosexual aspects of romantic relationships and body image. Results suggest that, overall, AYA cancer survivors experience a substantial burden of sexual dysfunction. Both physical and psychosocial sequelae influence survivors' sexual health. Interventions to support sexual health and psychosexual adjustment after cancer treatment are needed. Collaborations between the Children's Oncology Group and adult-focused cooperative groups within the National Cancer Institute's National Clinical Trials Network are warranted to advance prospective assessment of sexual dysfunction and test interventions to improve sexual health among AYA cancer survivors.
My Website: https://www.selleckchem.com/products/Trichostatin-A.html
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