Fishersavage6479

Cerebrovascular impairment contributes to the pathogenesis of Alzheimer's disease (AD). However, it still lacks effective intervention in clinical practice. Here, we investigated the efficacy of electroacupuncture (EA) in cerebrovascular repair in 3xTg-AD mice and its mechanism.

3xTg-AD mice were employed to evaluate the protective effect of EA at ST36 acupoint (EAST36). Behavioral tests were performed to assess neurological disorders. Laser speckle contrast imaging, immunostaining, and Western blot were applied to determine EAST36-boosted cerebrovascular repair. The mechanism was explored in 3xTg mice and endothelial cell cultures by melatonin signaling modulation.

EAST36 at 20/100 Hz effectively alleviated the olfactory impairment and anxiety behavior and boosted cerebrovascular repair in AD mice. EAST36 attenuated cerebral microvascular degeneration in AD mice by modulating endothelial cell viability and injury. Consequently, the Aβ deposits and neural damage in AD mice were reversed after EAST36. Mechanistically, we revealed that EAST36 restored melatonin levels in AD mice. Melatonin supplement mimicked the EAST36 effect on cerebrovascular protection in AD mice and endothelial cell cultures. Importantly, blockage of melatonin signaling by antagonist blunted EAST36-induced cerebrovascular recovery and subsequent neurological improvement.

These findings provided strong evidence to support EAST36 as a potential nonpharmacological therapy against cerebrovascular impairment in AD. Further study is necessary to better understand how EAST36 treatment drives melatonin signaling.

These findings provided strong evidence to support EAST36 as a potential nonpharmacological therapy against cerebrovascular impairment in AD. Further study is necessary to better understand how EAST36 treatment drives melatonin signaling.Progressive supranuclear palsy (PSP) is a primary tauopathy affecting both neurons and glia and is responsible for both motor and cognitive symptoms. Recently, it has been suggested that PSP tauopathy may spread in the brain from cell to cell in a "prion-like" manner. However, direct experimental evidence of this phenomenon, and its consequences on brain functions, is still lacking in primates. In this study, we first derived sarkosyl-insoluble tau fractions from post-mortem brains of PSP patients. We also isolated the same fraction from age-matched control brains. Compared to control extracts, the in vitro characterization of PSP-tau fractions demonstrated a high seeding activity in P301S-tau expressing cells, displaying after incubation abnormally phosphorylated (AT8- and AT100-positivity), misfolded, filamentous (pFTAA positive), and sarkosyl-insoluble tau. We bilaterally injected two male rhesus macaques in the supranigral area with this fraction of PSP-tau proteopathic seeds, and two other macaques with ved tau aggregates can induce motor and behavioral impairments in non-human primates related to the prion-like seeding and spreading of typical pathological PSP lesions. This pilot study pave the way for supporting PSP-tau injected macaque as a relevant animal model to accelerate drug development targeting this rare and fatal neurodegenerative disease.Despite the advantages of mathematical bioprocess modeling, successful model implementation already starts with experimental planning and accordingly can fail at this early stage. For this study, two different modeling approaches (mechanistic and hybrid) based on a four-dimensional antibody-producing CHO fed-batch process are compared. Overall, 33 experiments are performed in the fractional factorial four-dimensional design space and separated into four different complex data partitions subsequently used for model comparison and evaluation. The mechanistic model demonstrates the advantage of prior knowledge (i.e., known equations) to get informative value relatively independently of the utilized data partition. The hybrid approach displayes a higher data dependency but simultaneously yielded a higher accuracy on all data partitions. Furthermore, our results demonstrate that independent of the chosen modeling framework, a smart selection of only four initial experiments can already yield a very good representation of a full design space independent of the chosen modeling structure. Academic and industry researchers are recommended to pay more attention to experimental planning to maximize the process understanding obtained from mathematical modeling.In rural, Indigenous Guatemala, women's healthcare is fragmented and inadequate. Our interdisciplinary, multinational research team aimed to 1) describe reproductive health in one rural Indigenous community; 2) explore contraceptive use; and 3) learn about and prioritize Indigenous Maya women's reproductive health beliefs and needs. Our study team conducted mixed-methods surveys with 62 women, led focus groups with 20 community health workers, and analyzed data using concurrent mixed methods analysis. We found that 51% of women surveyed reported current family planning, with 33% using a biomedical method. We found high mean fertility, 6.9 live births per woman aged 40-49 (national average 4.7), with significant socioeconomic variation. We also found that poverty correlated with total fertility, while education inversely correlated. Our research found that contraceptive use had a strong association with access to healthcare and with women's reported sexual autonomy (which we instrumentalized based on women's answers to the question "can you refuse to have sex with your husband?"). Many women we spoke to feared contraception, specifically concerned it could cause cancer. Overall, Guatemalan Indigenous women expressed unease seeking reproductive healthcare within health systems that have historically and currently excluded and mistreated Indigenous communities. Our research documented unexplored influences on contraceptive use, including the relationship between sexual autonomy and contraception and widespread concern of cancer with contraceptive use. We conclude, moving forward, that we and other researchers should continue to collaborate with communities to improve Indigenous women's reproductive healthcare.With the ever-increasing abundance of biomedical articles, improving the accuracy of keyword search results becomes crucial for ensuring reproducible research. However, keyword extraction for biomedical articles is hard due to the existence of obscure keywords and the lack of a comprehensive benchmark. PubMedAKE is an author-assigned keyword extraction dataset that contains the title, abstract, and keywords of over 843,269 articles from the PubMed open access subset database. This dataset, publicly available on Zenodo, is the largest keyword extraction benchmark with sufficient samples to train neural networks. Experimental results using state-of-the-art baseline methods illustrate the need for developing automatic keyword extraction methods for biomedical literature.The 2013-2016 Ebola virus disease (EVD) epidemic caused food insecurity during and immediately following local outbreaks in Sierra Leone, but longer-term effects are less well described, particularly among households with no EVD survivors. We conducted a qualitative sub-study in July 2018 in Kono District, Sierra Leone to understand the impact of food insecurity on EVD-affected households. Using data from a community-based cohort, we compiled a list of all households, within the sampled communities in Kono District, that had at least one EVD case during the epidemic. We used purposive sampling to recruit 30 households, inclusive of 10 households with no EVD survivors, to participate in the study. The research team conducted open-ended, semi-structured interviews with the head of each household. All 30 interviews were transcribed, translated, and analyzed using comparative content analysis consistent with a grounded theory approach. Most household members were facing persistent food insecurity as direct or indirect consequences of the EVD epidemic, regardless of whether they did or did not live with EVD survivors. Three major themes emerged as drivers and/or mitigators of EVD-related food insecurity. Financial instability and physical health complications were drivers of food insecurity in the population, whereas support provided by NGOs or governmental agencies was observed as a mitigator and driver of food insecurity after its removal. Among the EVD-households reporting long-term support through jobs and educational opportunities, there was sustained mitigation of food insecurity. EVD-affected households with and without survivors continue to face food insecurity three years after the EVD epidemic. Provision of support was a mitigator of food insecurity in the short term, but its removal was a driver of food insecurity in the longer term, suggesting the need for longer-term transitional support in affected households.Actual loss of lizard biodiversity continues, even with the implementation of conventional conservation programs. An approach including assisted reproductive techniques such as sperm cryopreservation may contribute to the management of endangered species. We developed a method for sperm cryopreservation in sceloporine lizards and compared the response among the studied species. Prior to the mating season, we obtained semen from adult males of Sceloporus aeneus (n = 21), Sceloporus grammicus (n = 20) and Sceloporus torquatus (n = 21) via pressure of the genital papilla. Volume and sperm concentration were measured before semen dilution in a Tris-egg yolk (TEY) medium to evaluate progressive motility, sperm viability, morphology, plasma membrane and acrosome integrity. Then, we cooled the remaining volumes to 5°C at a rate of 0.1°C per minute to incorporate glycerol (8% v/v) in two fractions. Immediately afterwards, we placed 40 μl of the mix on solid CO2 to form pellets and immersed them in liquid nitrogen for storage. We thawed the pellets at 29°C for 3 minutes and diluted them 11 (v/v) in TEY medium to assess sperm quality. We found a positive relationship between body weight and seminal volume in S. Linsitinib mw grammicus and S. torquatus and a negative correlation with sperm concentration in S. grammicus (P  less then  0.05). Moreover, we observed that the freezing-thawing process decreased sperm quality in the three species, mostly affecting motility and viability. However, S. torquatus and S. aeneus showed a higher sperm tolerance than S. grammicus.

Administrative databases are increasingly used in research studies to capture clinical outcomes such as sepsis. This systematic review and meta-analysis examines the accuracy of

, 10th revision (ICD-10), codes for identifying sepsis in adult and pediatric patients.

We searched MEDLINE, EMBASE, Web of Science, CENTRAL, Epistemonikos, and McMaster Superfilters from inception to September 7, 2021.

We included studies that validated the accuracy of sepsis ICD-10 codes against any reference standard.

Three authors, working in duplicate, independently extracted data. We conducted meta-analysis using a random effects model to pool sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). We evaluated individual study risk of bias using the Quality Assessment of Diagnostic Accuracy Studies tool and assessed certainty in pooled diagnostic effect measures using the Grading of Recommendations Assessment, Development, and Evaluation framework.

Thirteen eligible studies were included in the qualitative synthesis and the meta-analysis.