Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson's Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway.

We assessed the antioxidant potential of narcissoside from Sambucus nigra flowers (elderflowers) in Parkinson's disease models in vitro and in vivo. The results showed that narcissoside lessened the 6-hydroxydopamine (6-OHDA)-induced increase in reactive oxygen species (ROS) and apoptosis in SH-SY5Y cells. In the 6-OHDA-exposed Caenorhabditis elegans model, narcissoside reduced degeneration of dopaminergic neurons and ROS generation, and also improved dopamine-related food-sensitive behavior and shortened lifespan. Moreover, NCS increased total glutathione (GSH) by increasing the expression of the catalytic subunit and modifier subunit of γ-glutamylcysteine ligase in cells and nematodes. Treatment with a GSH inhibitor partially abolished the anti-apoptotic ability of narcissoside. Furthermore, narcissoside diminished the 6-OHDA-induced phosphorylation of JNK and p38, while rising activities of ERK and Akt in resisting apoptosis. The antioxidant response element (ARE)-luciferase reporter activity analysis and electromobility gel shift assay showed that narcissoside promotes the transcriptional activity mediated by Nrf2. Finally, we found that narcissoside augmented the expression of miR200a, a translational inhibitor of the Nrf2 repressor protein Keap1. Downregulation of Nrf2 and miR200a by RNAi and anti-miR200a, respectively, reversed the neuroprotective ability of narcissoside. In summary, narcissoside can enhance the miR200a/Nrf2/GSH antioxidant pathway, alleviate 6-OHDA-induced apoptosis, and has the neuroprotective potential.

Humanitarian Mission in Pediatric Cardiothoracic Surgery: A Recipient's Perspective.

Introduction: Pediatric cardiac surgical mission programs are deemed as common practice, especially in developing nations funded by international non-governmental organizations (NGOs). This article presents and discusses the results and strategies implemented by this partnership, aiming at achieving the autonomy of the local center by this collaboration. Materials and Methods: A retrospective review was conducted on patients with congenital heart disease who underwent surgical intervention from the beginning of the NGO collaboration (September 2015) until November 2018 in an existing cardiac center. In between those visits, any congenital heart disease patient with Risk Adjustment Congenital Heart Surgery (RACHS)-1 Category 1-3 would be discussed in a local multi-disciplinary meeting with regards to the feasibility of the surgery being performed by the local members. Results: A total of 60 operations were performed during the trips. Throughout the visit, 46% (28) of the operations were performed by the local surgeon, with or without assistance from the visiting surgeon. Between September 2015 and November 2018, 27 cases were also performed by the local team independently. For the 27 cases performed by the local team independently, the median age of the patient was 42 days (ranging from 14 days to 20 years old), with median body weight of 3.2 kg (ranging from 2.8 to 64 kg). Conclusion: Humanitarian pediatric cardiac surgical missions are safe to be done for the population in need. In order to achieve autonomy, continuous efforts by both teams are crucial, as the cooperation by the two parties ensures that the objectives are achieved.

Surgery for doubly committed ventricular septal defects.

OBJECTIVES: Doubly committed ventricular septal defects (VSDs) account for up to almost one-third of isolated ventricular septal defects in Asian countries, compared with only 1/20th in western populations. In our surgical experience, this type of defect accounted for almost three-quarters of our practice. To date, patch closure has been considered the gold standard for surgical treatment of these lesions. Our objectives are to evaluate the indications and examine the outcomes of surgery for doubly committed VSDs. METHODS: Between October 2013, when our service of paediatric cardiac surgery was opened, and December 2014, 24 patients were referred for surgical closure of VSDs. Among them, 17 patients (71%), with the median age of 6 years, ranging from 2 to 9 years, and with a median body weight of 19 kg, ranging from 11 to 56 kg, underwent surgical repair for doubly committed defects. In terms of size, the defect was considered moderate in 4 and large in 13. Aortic valvular regurgitation (AoVR) was present in 11 patients (65%) preoperatively, with associated malformations found in 14 (82%), with 5 patients (29%) having two or more associated defects. RESULTS: After surgery, there was trivial residual shunting in 2 patients (12%). AoVR persisted in 6 (35%), reducing to trivial in 5 (29%) and mild in 1 (6%). Mean stays in the intensive care unit and hospital were 2.6 ± 1.2 days, ranging from 2 to 7 days, and 6.8 ± 0.8 days, ranging from 6 to 9 days, respectively. The mean follow-up was 14 ± 4 months, ranging from 6 to 20 months, with no early or late deaths and without clinical deterioration. CONCLUSIONS: The incidence of doubly committed lesions is high in our experience, frequently associated with AoVR and other associated malformation. Early detection is crucial to prevent further progression of the disease. Patch closure remains the gold standard in management, not least since it allows simultaneous repair of associated intracardiac defects.

Irisflorentin improves α-synuclein accumulation and attenuates 6-OHDA-induced dopaminergic neuron degeneration, implication for Parkinson's disease therapy.

Parkinson's disease (PD) is a degenerative disorder of the central nervous system that is characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta as well as motor impairment. Aggregation of α-synuclein in neuronal cells plays a key role in this disease. At present, therapeutics for PD provides moderate symptomatic benefits, but it is not able to delay the development of the disease. Current efforts toward the treatment of PD are to identify new drugs that slow or arrest the progressive course of PD by interfering with a disease-specific pathogenetic process in PD patients. Irisflorentin derived from the roots of Belamcanda chinensis (L.) DC. is an herb which has been used for the treatment of inflammatory disorders in traditional Chinese medicine. The purpose of the present study was to assess the potential for irisflorentin to ameliorate PD in Caenorhabditis elegans models. Our data reveal that irisflorentin prevents α-synuclein accumulation in the transgenic Caenorhabditis elegans model and also improves dopaminergic neuron degeneration, food-sensing behavior, and life-span in a 6-hydroxydopamine-induced Caenorhabditis elegans model, thus indicating its potential as a anti-parkinsonian drug candidate. Irisflorentin may exert its effects by promoting rpn-3 expression to enhance the activity of proteasomes and down-regulating egl-1 expression to block apoptosis pathways. These findings encourage further investigation on irisflorentin as a possible potent agent for PD treatment.

Comparative study of multimedia models applied to the risk assessment of soil and groundwater contamination sites in Taiwan.

The purpose of this study was to explore the applicability of two popular multimedia risk assessment models to three different soil and groundwater contamination sites in Taiwan. The Multimedia Environmental Pollutant Assessment System (MEPAS) and the Multimedia Contaminant Fate, Transport, and Exposure Model (MMSOILS) were selected because of their wide application and use. Three soil and groundwater contamination sites in Taiwan were employed as illustrative examples in the comparison of these two risk assessment models. Three exposure pathways were investigated, categorized as oral ingestion, dermal absorption, and inhalation. The results show that MEPAS and MMSOILS calculated similar cancer risks and hazard quotients in general, but were different by two orders of magnitude in cancer risk estimates for sites contaminated by volatile organic compounds (VOC). Using MMSOILS may not be appropriate for risk assessment of such sites, as it does not account for indoor inhalation as a potential exposure pathway in its risk calculations. Water ingestion, dermal absorption when showering and indoor inhalation were the three most predominant contributing exposure pathways for risk development among sites contaminated by VOCs. On the other hand, crop and meat ingestion were more important exposure pathways in the context of sites with non-VOC pollutants, because these hydrophobic contaminants may be bio-accumulative in plants and animals, and consequently enter the human body via food chains.

The Health Risk assessment of Pb and Cr leached from fly ash monolith landfill.

As of 2004, nearly two hundred thousand tons of fly ash monoliths are created each year in Taiwan to confine heavy metals for reducing the leaching quantity by precipitation. However, due to abnormal monolith fracture, poorly liner quality or exceeding usage over designed landfill capacity, serious groundwater pollution of the landfills has been reported. This research focuses on Pb and Cr leaching from monolithic landfill to assess the risk of groundwater pollution in the vicinity. The methodology combines water budget simulations using HELP model with fate and risk simulations using MMSOILS model for 5 kinds of landfill structures and 2 types of leaching models, and calculates the risk distribution over 400 grids in the down gradient direction of groundwater. The results demonstrated that the worst liner quality will cause the largest risk and the most significant exposure pathway is groundwater intake, which accounted for 98% of the total risk. Comparing Pb and Cr concentrations in the groundwater with the drinking water standards, only 14.25% of the total grids are found to be under 0.05 mg/L of Pb, and over 96.5% of the total grids are in the safety range of Cr. It indicates that Pb leaching from fly ash monolithic landfills may cause serious health risks. Without consideration of the parameters uncertainty, the cancer and noncancer risk of Pb with the sanitary landfill method was 4.23E-07 and 0.63, respectively, both under acceptable levels. However, by considering the parameters uncertainty, the non-carcinogenic risk of Pb became 1.43, exceeding the acceptable level. Only under the sealed landfill method was the hazard quotient below 1. It is important to use at least the sealed landfill for fly ash monoliths containing lead to effectively reduce health risks.

Risk assessment of exposure to volatile organic compounds in groundwater in Taiwan.

The purpose of this study is to assess the risks from exposure to 14 volatile organic compounds (VOCs) in selected groundwater sites in Taiwan. The study employs the multimedia environment pollutant assessment system (MEPAS) model to calculate the specific non-cancer and cancer risks at an exposure level of 1 microg/L of each VOC for a variety of exposure pathways. The results show that the highest specific non-cancer risk is associated with water ingestion of vinyl chloride (VC) and that the highest specific cancer risk is associated with indoor breathing of VC. The three most important exposure pathways for risk assessment for both non-cancer and cancer risks are identified as water ingestion, dermal absorption when showering, and indoor breathing. Excess tetrachloroethylene (PCE), trichloroethylene (TCE), dichloroethylene (DCE), and VC are detected in the groundwater aquifers of one dump site and one factory. However, the study suggests that the pollutants in the contaminated groundwater aquifers do not travel extensively with groundwater flow and that the resulting VOC concentrations are below detectable levels for most of the sampled drinking-water treatment plants. Nevertheless, the non-cancer and cancer risks resulting from use of the contaminated groundwater are found to be hundred times higher than the general risk guidance values. To ensure safe groundwater utilisation, remediation initiatives for soil and groundwater are required. Finally, the study suggests that the current criteria for VOCs in drinking water might not be capable of ensuring public safety when groundwater is used as the primary water supply; more stringent quality criteria for drinking water are proposed for selected VOCs.

Preparation, electrochemical and spectral properties of free-base and manganese N-methyl-pyridylethynyl porphyrins.

Two series of free-base and manganese N-methyl-pyridylethynyl-5,15-biphenyl porphyrins were synthesized, and their UV-Visible, electrochemical and spectro-electrochemical properties were studied. Cyclic voltammetry experiments showed positive shifts in the reduction potentials and the UV-Visible spectra showed significant red-shifts in the absorption wavelengths of these porphyrins, indicating the effects of N-methyl-pyridylethynyl substituents.

Combining the cost of reducing uncertainty with the selection of risk assessment models for remediation decision of site contamination.

The decision as to whether a contaminated site poses a threat to human health and should be cleaned up relies increasingly upon the use of risk assessment models. However, the more sophisticated risk assessment models become, the greater the concern with the uncertainty in, and thus the credibility of, risk assessment. In particular, when there are several equally plausible models, decision makers are confused by model uncertainty and perplexed as to which model should be chosen for making decisions objectively. When the correctness of different models is not easily judged after objective analysis has been conducted, the cost incurred during the processes of risk assessment has to be considered in order to make an efficient decision. In order to support an efficient and objective remediation decision, this study develops a methodology to cost the least required reduction of uncertainty and to use the cost measure in the selection of candidate models. The focus is on identifying the efforts involved in reducing the input uncertainty to the point at which the uncertainty would not hinder the decision in each equally plausible model. First, this methodology combines a nested Monte Carlo simulation, rank correlation coefficients, and explicit decision criteria to identify key uncertain inputs that would influence the decision in order to reduce input uncertainty. This methodology then calculates the cost of required reduction of input uncertainty in each model by convergence ratio, which measures the needed convergence level of each key input's spread. Finally, the most appropriate model can be selected based on the convergence ratio and cost. A case of a contaminated site is used to demonstrate the methodology.

Model comparison for risk assessment: a case study of contaminated groundwater.

Many environmental multimedia risk assessment models have been developed and widely used along with increasing sophistication of the risk assessment method. Despite of the considerable improvement, uncertainty remains a primary threat to the credibility of and users' confidence in the model-based risk assessments. In particular, it has been indicated that scenario and model uncertainty may affect significantly the assessment outcome. Furthermore, the uncertainty resulting from choosing different models has been shown more important than that caused by parameter uncertainty. Based on the relationship between exposure pathways and estimated risk results, this study develops a screening procedure to compare the relative suitability between potential multimedia models, which would facilitate the reduction of uncertainty due to model selection. MEPAS, MMSOILS, and CalTOX models, combined with Monte Carlo simulation, are applied to a realistic groundwater-contaminated site to demonstrate the process. It is also shown that the identification of important parameters and exposure pathways, and implicitly, the subsequent design of uncertainty reduction and risk management measures, would be better-formed.