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Age-related macular degeneration (AMD) is a leading cause for visual impairment in aging populations with limited established therapeutic interventions available. Oxidative stress plays an essential role in the pathogenesis of AMD, damaging the retinal pigment epithelium (RPE), which is essential for the function and maintenance of the light-sensing photoreceptors. This study aimed to evaluate the effects of crocetin, one of the main components of Saffron, on an in vitro RPE model of tert-butyl hydroperoxide (TBHP) induced oxidative stress using ARPE19 cells. The effects of crocetin were assessed using lactate de-hydrogenase (LDH) and ATP assays, as well as immunocytochemistry for cell morphology, junctional integrity, and nuclear morphology. The mechanism of crocetin action was determined via assessment of energy production pathways, including mitochondrial respiration and glycolysis in real-time as well as investigation of extracellular signal-regulated kinase 1/2 (ERK1/2) activation and distribution. Our results show that crocetin pre-treatment protects ARPE19 cells from TBHP-induced LDH release, intracellular ATP depletion, nuclear condensation, and disturbance of junctional integrity and cytoskeleton. The protective effect of crocetin is mediated via the preservation of energy production pathways and activation of ERK1/2 in the first minutes of TBHP exposure to potentiate survival pathways. The combined data suggest that a natural antioxidant, such as crocetin, represents a promising candidate to prevent oxidative stress in RPE cells and might halt or delay disease progression in AMD.Along with animal production factors, it is important to understand whether demographic factors influence untrained consumer perceptions of eating quality. This study examined the impact of demographic factors and sheepmeat consumption preferences on eating quality scores of American, Australian and Chinese untrained consumers. M. longissimus lumborum (LL) and m. semimembranosus (SM) were grilled according to sheep Meat Standards Australia protocols and evaluated by 2160 consumers for tenderness, juiciness, flavour and overall liking. Linear mixed effects models were used to analyse the impact of demographic factors and sheepmeat consumption habits on eating quality scores. Consumer age, gender, number of adults in a household and income had the strongest effect on sensory scores (P ≤ 0.05), although, the impact was often different across countries. Frequency of lamb consumption had an impact on sensory scores of American, Australian and Chinese consumers but larger sample sizes in some underrepresented subclasses for Australian and Chinese consumers are needed. Results suggest it is important to balance sensory panels for demographic factors of age, gender, number of adults and income to ensure sensory preferences are accurately represented for these particular populations.Several cytochrome P450 (CYP) CYP3A polymorphisms were associated with reduced enzyme function. We aimed to evaluate the influence of these alleles on the pharmacokinetic parameters (PK) of several CYP3A substrates. We included 251 healthy volunteers who received a single dose of ambrisentan, atorvastatin, imatinib, aripiprazole, fentanyl, amlodipine, donepezil, olanzapine, fesoterodine, or quetiapine. The volunteers were genotyped for CYP3A4 and CYP3A5 polymorphisms by qPCR. To compare the PK across studies, measurements were corrected by the mean of each parameter for every drug and were logarithmically transformed. Neither CYP3A phenotype nor individual CYP3A4 or CYP3A5 polymorphisms were significantly associated with differences in PK. However, regarding the substrates that are exclusively metabolized by CYP3A, we observed a higher normalized AUC (p = 0.099) and a tendency of lower normalized Cl (p = 0.069) in CYP3A4 mutated allele carriers what was associated with diminished drug metabolism capacity. CYP3A4 polymorphisms did not show a pronounced influence on PK of the analysed drugs. If so, their impact could be detectable in a very small percentage of subjects. Although there are few subjects carrying CYP3A4 double mutations, the effect in those might be relevant, especially due to the majority of subjects lacking the CYP3A5 enzyme. In heterozygous subjects, the consequence might be less noticeable due to the high inducible potential of the CYP3A4 enzyme.Background The global push to achieve the 90-90-90 targets designed to end the HIV epidemic has called for the removing of policy barriers to prevention and treatment, and ensuring financial sustainability of HIV programs. Universal health insurance is one tool that can be used to this end. In sub-Saharan Africa, where HIV prevalence and incidence remain high, the use of health insurance to provide comprehensive HIV care is limited. This study looked at the factors that best predict social health insurance enrollment among HIV positive pregnant women using data from the Academic Model Providing Access to Healthcare (AMPATH) in western Kenya. Methods Cross-sectional clinical encounter data were extracted from the electronic medical records (EMR) at AMPATH. We used univariate and multivariate logistic regressions to estimate the predictors of health insurance enrollment among HIV positive pregnant women. The analysis was further stratified by HIV disease severity (based on CD4 cell count ) to test the possibilif healthcare facilities, increased the likelihood of health insurance enrollment within this population. selleck However, behavioral aspects, such as being lost to follow-up to HIV care during pregnancy and being on HIV treatment, had an ambiguous effect on insurance enrollment. This may potentially be because of adverse selection and information asymmetries. Further understanding of the relationship between insurance and HIV is needed if health insurance is to be utilized for HIV treatment and prevention in limited resource settings.Breast cancer is a common malignancy threatening women's health around the world. Despite improved treatments for different subtypes of breast tumors that have been put forward, there still exists a poor therapeutic response and prognosis. Magnetic fields, as a non-invasive therapy, have shown anti-tumor effects in vitro and in vivo; however, the detailed mechanisms involved are still not clear. In this study, we found that in exposure to low-frequency magnetic fields (LF-MFs) with an intensity of 1 mT and frequencies of 50, 125, 200, and 275 Hz, separately, the proliferation of breast cancer cells was inhibited and LF-MF with 200 Hz reached the optimum inhibition effect, on exposure time-dependently. Notably, we found that exposure to LF-MF led to MCF-7 and ZR-75-1 cell apoptosis and cell cycle arrest. Moreover, we also discovered that LF-MF effectively increased the level of reactive oxygen species (ROS), suppressed the PI3K/AKT signaling pathway, and activated glycogen synthase kinase-3β (GSK-3β). We demonstrated that the GSK3β activity contributed to LF-MF-induced cell proliferation inhibition and apoptosis, while the underlying mechanism was associated with the inhibition of PI3K/AKT through increasing the intracellular ROS accumulation.

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