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Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. The association between AD and other diseases such as diabetes is well-studied. In parallel, potential disease-modifying effects of therapeutic agents used for diabetes have been investigated in the context AD of. Metformin is a biguanide and the most commonly prescribed medication for type 2 diabetes Due to its pleiotropic properties, metformin's potential disease-modifying effects are widely studied on different pathophysiological plyers of AD such as amyloid-β (Aβ) production and clearance, tau phosphorylation, and neuroinflammation, in relevant in vitro and in vivo models. In this review, we summarize the relevant scientific literature on the effects of metformin on various aspects of AD pathophysiology.
Influenza is a leading cause of community-acquired pneumonia (CAP), and results of influenza tests can direct therapy. However, among adults hospitalized with CAP, little is known about the frequency and timing of influenza testing, treatment, and their associations with outcomes.
In patients with CAP, is testing for influenza associated with antiviral treatment and shorter antibiotic courses, and is early treatment associated with better clinical outcomes?
This study included adults admitted with pneumonia in 2010 to 2015 to 179 US hospitals contributing to the Premier database. We assessed influenza testing and compared antimicrobial utilization and the outcomes of test-positive, test-negative, and untested patients. Associations of early antiviral treatment (oseltamivir) with 14-day in-hospital mortality, hospital length of stay, and cost were studied.
Among 166,268 patients with CAP, 38,703 (23.3%) were tested for influenza, of whom 11.5%tested positive. Testing increased from 15.4%to 35.6%from 20 influenza. A positive influenza test result was associated with antiviral treatment, and early treatment was associated with lower mortality, suggesting that more widespread testing might improve patient outcomes.Combined oral contraceptives (COCs) are commonly used by individuals for contraceptive and noncontraceptive purposes, such as the management of dysmenorrhea or to reduce risk for ovarian and endometrial cancer. However, a common consideration that continues to arise is whether COC use increases breast cancer risk. Many researchers have investigated this, but study results are varied and may be affected by variables such as hormone type, an individual's age, and the duration of COC use. In this article, we summarize select breast cancer risk considerations regarding COC use to assist clinicians when counseling individuals considering using oral contraceptives.Neuronal target recognition is performed by numerous cell-surface transmembrane proteins. Correct folding of these proteins occurs in the endoplasmic reticulum (ER) lumen of the neuronal cells before being transported to the plasma membrane of axons or dendrites. Disturbance in this protein folding process in the ER leads to dysfunction of neuronal cell surface molecules, resulting in abnormal neuronal targeting. In this study, we report that the ER-resident protein Meigo in Drosophila, governs the dendrite targeting of olfactory projection neurons (PNs) along the mediolateral axis of the antennal lobe by regulating Toll-6 localization. Loss of Meigo causes Toll-6 mislocalization in the PNs and mediolateral dendrite targeting defects, which are suppressed by Toll-6 overexpression. Furthermore, we found that the ER-chaperone protein, Gp93, also regulates the mediolateral targeting of PN dendrites by localization of the Toll-6 protein. Gp93 overexpression in the PN homozygous for the meigo mutation, partially rescued the dendrite targeting defect, while meigo knockdown decreased Gp93 expression levels in cultured cells. These results indicate that the ER-proteins Meigo and Gp93 regulate dendrite targeting by attenuating the amount and localization of cell surface receptors, including Toll-6, implying the unexpected but active involvement of ER proteins in neural wiring.The distribution, partitioning behavior, and diffusion of polycyclic aromatic hydrocarbons (PAHs) within sediment-porewater system were determined in two cores obtained from the Min-Zhe coastal mud of the East China Sea (ECS). Depth profiles of apparently dissolved PAH levels exhibited greater variabilities, with their elevated levels at depth and a high abundance of two-to three-ring PAHs observed. These distribution and composition patterns were inconsistent with the corresponding sediment PAHs, indicating differences in controlling factors for PAHs present in the system. In addition to compound's hydrophobicity, low detection of heavier PAHs in porewater was possibly correlated with the sediment transport process, as indicated by a relatively high weathering ratio in southern Min-Zhe coastal mud. PAH sorption affinity to the collected core sediments exhibited a generally decreasing trend downcore, as expressed by sediment-porewater partition coefficients. This was consistent with the higher content of porewater PAHs in deep core sediment. The established sediment total organic carbon (TOC)-porewater partitioning profiles in cores were predicted with amorphous organic carbon (AOC)-, coal tar-, and TOC-based distribution models, suggesting a dominant nonlinear sorption of PAHs to AOC. Through activity determinations, PAH diffusion within porewater was elucidated, with significant upward and downward mass transfer for PAHs occurring in both cores. The upward diffusion in the core collected from northern Min-Zhe coastal mud was in significant association with sediment TOC. This suggests that sediment TOC (especially AOC)-desorption of lighter PAHs into porewater, and therefore the possibility of their participation in environmental cycling. Baseline toxicity potential and toxic unit calculations indicated a relatively low exposure risk for benthic organisms to porewater PAHs.The impact of odorous gases emitted from refuse transfer stations has always been a concern raised by the surrounding residents. The emitted volatile organic compounds (VOCs) and odors were investigated in a rural solid waste transfer station (RSWTS) located in Southwest China. A total of 70 VOCs were identified and quantified. The total VOCs (TVOCs) concentrations varied from 848.38 to 31193.24 μg/m3. Inorganic odor and greenhouse gases concentrations ranged from 39.11 to 470.14 μg/m3 and 1.03-525.42 μg/m3, respectively. Oxygenated compounds contributed the most (58.25%) to the VOCs. Among the oxygenated compounds, ketones, esters, and ethers were the dominant categories, accounting for 67.5%, 12.70%, and 11.85%, respectively. The key odorants included propionaldehyde, hexanaldehyde, propionic acid, acetaldehyde, and disopropyl ether. N-nitrosodiethylamine, acrylonitrile, and 1,3-Butadiene were the three main carcinogens that pose considerable risk to human health. Allyl chloride was the most non-carcinogenic pathogen among the VOCs detected in RSWTS. With diffusion in the downwind direction, the concentration of VOCs decreased gradually, and their risks weakened accordingly. At the sampling site of RSWTS-10, located 100 m away from RSWTS, acrylonitrile and 1,3-Butadiene still presented an unacceptable carcinogenic risk to human health. This study provides new data for assessing the emission characteristics, olfactory effects, and health risks of trace VOCs, especially those released from RSWTS.
There has been increasing attention on the associations between ambient particulate matter (PM) in early-life and neurodevelopmental disorders (NDDs). However, the associations remained unclear when considering different types of NDDs and different sizes of PM, and vulnerable exposure windows during early-life were not identified yet.
To synthesize the published literature on the associations between ambient particulate matter (PM) and risk of different types of neurodevelopmental disorders (NDDs) in a systematic review and meta-analysis.
A systematic search of Medline, Embase, PubMed, Cochrane Library, and Web of Science was performed from inception through 24 January 2022. Two reviewers conducted the study selection, data extraction, and quality appraisal. A random-effects model was used for meta-analyses with two quality-of-evidence assessments (the Grading of Recommendations Assessment, Development, and Evaluation system and the best evidence synthesis system).
A total of 6554 articles were screen appeared to be the critical exposure window. High-quality studies are needed to assess the evidence for other types of NDDs.
Long-term exposure to ambient ozone (O
) and residential greenness independently relate to altered hormones levels in urban settings and developed countries. However, independent and their joint associations with progestogen and androgen were sparsely studied in rural regions.
A total of 6211 individuals were recruited in this study. Random forest model was applied to predict the daily average concentrations of O
using the satellites data. Residential greenness was reflected by the normalized difference vegetation index (NDVI). Liquid chromatography-tandem mass spectrometry was used to measure serum progestogen and androgen concentrations. Gender and menopausal status modified associations of long-term exposure to O
and residential greenness with hormones levels were analyzed by generalized linear models.
Long-term exposure to O
was negatively related to 17-hydroxyprogesterone, testosterone, and androstenedione in both men and women (premenopausal and postmenopausal); the estimated β and 95% CI onness places in women regardless of menopause status. Future studies are needed to confirm the positive health effects of residential greenness on the potential detrimental effects due to exposure to O3.
The SARS-CoV-2 virus pandemic is primarily transmitted by direct contact between infected and uninfected people, though, there are still many unknown factors influencing the survival and transmission of the virus. Air temperature is one of the main susceptible factors. This study aimed to explore the impact of air and land surface temperatures on Covid-19 transmission in a region of Iran.
Daily Land Surface Temperature (LST) measured by satellite and Air Temperature measured by weather station were used as the predictors of Covid-19 transmission. The data were obtained from February 2020 to April 2021. Spatio-temporal kriging was used in order to predict LST in some days in which no image was recorded by the satellite. The validity of the predicted values was assessed by Bland-Altman technique. The impact of the predictors was analyzed by Distributed Lag Non-linear Model (DLNM). In addition to main effect of temperature, its linear as well as non-linear interaction effect with relative humidity were consis. Because of local based evidence, the wide confidence intervals and then non-significant values should be cautiously interpreted.In this study, the composition of mainstream smoke was investigated with an emphasis on a list of volatile organic compounds (VOCs e.g., isoprene, acrylonitrile, methyl ethyl ketone, benzene, toluene, m-xylene and styrene) using the two types of flavor capsule cigarettes (FCCs, here coded as F1 and F2) in reference to one commercial, non-flavored (NF) and 3R4F cigarette. The concentrations of all the target compounds from FCCs were quantified under two contrasting conditions (i.e., with and without breaking the capsules). The effect of breaking the capsule was apparent in the FCC products with the enhancement of VOC levels, specifically between after and before breaking the capsules (e.g., 1.10-1.58 folds (benzene) and 1.30-1.53 folds (acetonitrile)). Such increases were apparent in both FCC samples if assessed in terms of the total amount of VOCs (TVOC) (1) F1 (from 2159 to 2530 μg cig-1 (p = 9.42 × 10-6)) and (2) F2 (from 1470 to 2014 μg cig-1 (p = 0.05)). In addition, these TVOC levels determined from the FCCs were 1.