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Findings on the association between statin therapy and Parkinson's disease (PD) occurrence have been inconsistent. This study aimed to identify the association between statin use and PD in participants with a history of hyperlipidemia or blood cholesterol >200 in a Korean population to exclude nonstatin users owing to normal lipid values.

We conducted a nested case-control analysis using the Korean National Health Insurance Service-National Sample Cohort assessed between 2002 and 2015. We identified 3026 PD cases. A total of 12,104 controls were then individually matched by age, sex, income, and region of residence at a ratio of 14. Potential confounders comprised basic demographic factors, lifestyle factors, various medical conditions and comorbidities. A conditional/unconditional logistic regression method was applied.

Compared with statin use for <6 months, adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for 6-12 months of statin use and ≥12 months of statin use were 1.03 (0.92-1.15) and 1.61 (1.35-1.93) after adjustment for confounders, respectively (P=0.664 and P<0.001). In analyses according to statin solubility, only the association between lipophilic statin use for ≥12 months and PD maintained statistical significance, with an aOR of 1.64 (95% CI=1.34-2.01, P<0.001). These relations were consistent in subgroup analyses by covariates.

Statin use for more than 12 months was associated with a higher probability of PD in the Korean population with hyperlipidemia. This probability was significant for lipophilic statins but not hydrophilic statins.

Statin use for more than 12 months was associated with a higher probability of PD in the Korean population with hyperlipidemia. This probability was significant for lipophilic statins but not hydrophilic statins.

This study investigated the relationship between white matter hyperintensities (WMHs), nigrostriatal dopamine deficits, and cognitive decline in patients with drug-naïve early-stage Parkinson's disease (PD).

This cross-sectional study enrolled 309 non-demented patients with de novo PD who underwent [

F] N-(3-fluoropropyl)-2β-carbonethoxy-3β-(4-iodophenyl) nortropane positron emission tomography, brain magnetic resonance imaging, and a detailed neuropsychological test at baseline. We quantified dopamine transporter (DAT) availability in each striatal sub-region and applied the Scheltens scale to assess the severity of periventricular and deep WMHs. The relationships between WMHs, DAT availability, and cognition in PD were assessed using multivariate linear regression and mediation analyses while adjusting for age at parkinsonian symptom onset, sex, disease duration, and vascular risk factors.

The severities of periventricular and frontal WMHs were associated with striatal DAT availability. Periventricular WMHs affected the level of cognitive performance in all cognitive domains, while frontal WMHs affected the attention/working memory and frontal/executive function domains. The effects of WMHs on attention/working memory and frontal/executive dysfunction were mostly direct with minimal mediating effects through striatal DAT availability. Meanwhile, striatal DAT availability fully mediated the association between WMHs and cognitive impairment in the visuospatial and memory function domains.

This study demonstrated the different effects of WMHs on cognitive impairment depending on the cognitive domains in PD. These findings suggest a close link between comorbid WMHs, striatal dopamine depletion, and cognition in patients with PD.

This study demonstrated the different effects of WMHs on cognitive impairment depending on the cognitive domains in PD. These findings suggest a close link between comorbid WMHs, striatal dopamine depletion, and cognition in patients with PD.Multiple sclerosis (MS) was one of the major conditions causing neurological dysfunction and was an incurable progressive central nervous system disease. Experimental autoimmune encephalomyelitis (EAE) was the most commonly used experimental model of MS. Artemisinin have been shown to exhibit anti-inflammatory effects through unclear mechanisms. In this study, we aimed to evaluate the effect of administration of the artemisinin derivative TPN10466 in EAE. TPN10466 alleviated the severity of disease in EAE. Further studies showed that TPN10466 inhibited lymphocyte migration by downregulating chemokine expression and adhesion molecules. In addition, studies showed that TPN10466 directly inhibited Th1 and Th17 differentiation and reduced Th1 and Th17 infiltration into the central nervous system. In conclusion, our work demonstrated that TPN10466 provided protection against the autoimmune disease EAE by inhibiting the migration of immune cells and suppressing Th1/Th17 differentiation, suggesting that TPN10466 could be a potential for promising potential agent for the treatment of MS/EAE.The various fibroblast growth factors (FGF) regulate their function via binding to 4 main FGF receptor (FGFR) subtypes and their splice variants, FGFR1b, FGF1c, FGFR2b, FGFR2c and FGFR3c and FGFR4, but which of these FGFR are expressed in the granulosa (GC) and theca cells (TC), the 2 main cell layers of ovarian follicles, or change during follicular development is unknown. We hypothesized that FGFR1c, FGFR2c and FGFR3c (but not FGFR4) gene expression in GC (but not TC) would change with follicular development. Hence, the objective of this study was to determine if abundance of FGFR1c, FGFR2c, FGFR3c, and FGFR4 mRNA change according to follicular size, steroidogenic status, and days post-ovulation during growth of first-wave dominant follicles in Holstein cattle exhibiting regular estrous cycles. Estrous cycles of non-lactating dairy cattle were synchronized, and ovaries were collected on either d 3 to 4 (n = 8) or d 5 to 6 (n = 8) post-ovulation for GC and TC RNA extraction from small (1-5 mm), medium (5.1 towing phase of the first dominant follicle support an anti-differentiation role for FGF and their FGFR as well as support the idea that steroid-induced changes in FGF and their receptors may regulate selection of dominant follicles in cattle.Three dimensional (3D) printing technology has pushed state-of-the-art manufacturing towards more advanced processing methods through its ability to produce complex computer-designed 3D structures in a wide range of materials. Two-photon polymerization applied to the fabrication of ultraprecise 3D microstructures is one of the various innovative approaches to cutting-edge 3D printing. The integration of an ultrashort pulsed laser source and an appropriate photoresist has made it an attractive candidate for advanced photonics and biomedical applications. This paper presents the development of 3D solid microneedle arrays as a novel transdermal drug delivery system via two-photon polymerization in a single manufacturing step. Through a series of experiments, the best fabrication parameters are identified. Finite element simulations are then performed to investigate the interaction between a single microneedle and human skin. The results of this study highlight the influence of fabrication parameters such as laser power, scanning speed, hatch distance and layer height on the structural resolution and fabrication time of microneedles, as well as human skin deformation caused through application of force to a single polymer microneedle.Lipid peroxidation (LPO) plays a key role in many age-related neurodegenerative conditions and other disorders. Light irradiation can initiate LPO through various mechanisms and is of importance in retinal and dermatological pathologies. The introduction of deuterated polyunsaturated fatty acids (D-PUFA) into membrane lipids is a promising approach for protection against LPO. Here, we report the protective effects of D-PUFA against the photodynamically induced LPO, using illumination in the presence of the photosensitizer trisulfonated aluminum phthalocyanine (AlPcS3) in liposomes and giant unilamellar vesicles (GUV), as assessed in four experimental models 1) sulforhodamine B leakage from liposomes, detected with fluorescence correlation spectroscopy (FCS); 2) formation of diene conjugates in liposomal membranes, measured by absorbance at 234 nm; 3) membrane leakage in GUV assessed by optical phase-contrast intensity observations; 4) UPLC-MS/MS method to detect oxidized linoleic acid (Lin)-derived metabolites. Specifically, in liposomes or GUV containing H-PUFA (dilinoleyl-sn-glycero-3-phosphatidylcholine), light irradiation led to an extensive oxidative damage to bilayers. By contrast, no damage was observed in lipid bilayers containing 20% or more D-PUFA (D2-Lin or D10-docosahexanenoic acid). Remarkably, addition of tocopherol increased the dye leakage from liposomes in H-PUFA bilayers compared to photoirradiation alone, signifying tocopherol's pro-oxidant properties. However, in the presence of D-PUFA the opposite effect was observed, whereby adding tocopherol increased the resistance to LPO. These findings suggest a method to augment the protective effects of D-PUFA, which are currently undergoing clinical trials in several neurological and retinal diseases that involve LPO.

Photodynamic therapy (PDT) activates a photosensitizer by visible light to generate cytotoxic oxygen species that lead to cell death. With proper illumination, PDT is often used in applications on superficial and sub-surface lesions. Sporotrichosis infection occurs by Sporothrix fungi which causes a skin wound, worsened by Candida albicans infections. This study investigated the photosensitizing efficiency of the Ru(phen)

(pPDIp)(PF

)

complex, RupPDIp, against S. brasiliensis and C. albicans.

RupPDIp efficiency against these fungi was tested using 450nm (blue light and 36J/cm

) and 525nm (green light, 25.2J/cm

) at 0.05-20μM concentrations. To ensure PDT effectiveness, control groups were tested in the absence and in the presence of RupPDIp under light irradiation and in the dark.

RupPDIp eliminated both fungi at ≤5.0μM. Green light showed the best results, eliminating S. brasiliensis and C. albicans colonies at RupPDIp 0.5μM and 0.05μM, respectively.

RupPDIp is a promising photosensitizer in aPDT, eliminating 10

CFU/mL of both fungi at 450nm and 525nm, with lower light doses and concentrations when treated with the green light compared to the blue light.

RupPDIp is a promising photosensitizer in aPDT, eliminating 106 CFU/mL of both fungi at 450 nm and 525 nm, with lower light doses and concentrations when treated with the green light compared to the blue light.In this study, a plant-wide model describing the fate of C, N and P compounds, upgraded to account for (on-site/off-site) greenhouse gas (GHG) emissions, was implemented within the International Water Association (IWA) Benchmarking Simulation Model No. find more 2 (BSM2) framework. The proposed approach includes the main biological N2O production pathways and mechanistically describes CO2 (biogenic/non-biogenic) emissions in the activated sludge reactors as well as the biogas production (CO2/CH4) from the anaerobic digester. Indirect GHG emissions for power generation, chemical usage, effluent disposal and sludge storage and reuse are also included using static factors for CO2, CH4 and N2O. Global and individual mass balances were quantified to investigate the fluxes of the different components. Novel strategies, such as the combination of different cascade controllers in the biological reactors and struvite precipitation in the sludge line, were proposed in order to obtain high plant performance as well as nutrient recovery and mitigation of the GHG emissions in a plant-wide context.

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