Psychiatric Advance Directives and their relevance to improving psychiatric care in Asian countries

People with mental illness may be unable to provide critical input about the care they wish to receive during a psychiatric crisis because of altered mental states. It is therefore imperative that clinicians seek to understand service users' wishes for care while they are well and able to provide meaningful input into the discussion. Achieving such an end may be done by discussing and completing a psychiatric advance directive. However, very few Asian countries have legislation that supports such advance directives. The present article seeks to give physicians more information about advance psychiatric directives and the potential role they could play to improve the healthcare provided in Asia to people at risk of losing capacity due to a mental illness. The degree to which mental health legislation supports psychiatric advance directives is documented for each country of South East Asia and Eastern Asia.     

Social media as a platform for science and health engagement: challenges and opportunities

Social media has become a major platform for debates on science and health. This commentary argues that while social media can present challenges to communicating important health matters, it can also provide health experts a unique opportunity to engage with and build trust among members of the public.     

The ecological risk of heavy metals in sediment from the Danube Delta

The objectives of this study were to assess the sediment contamination with heavy metals and to investigate accordingly the ecological risk posed in the SE of the Danube Delta. Sediments are important in assessing the contamination as they act as reservoirs, transporters and contamination sources. Sediment samples were collected and analysed for lead, cadmium, arsenic and mercury, revealing levels higher than the background, especially for cadmium and mercury (Pb > As > Cd > Hg). Concentrations exceeding the probable effect limit were noticed for arsenic and mercury. The contamination indexes describe the study area as having almost half of the samples as contaminated (pollution load index-PLI 1.04), however the contamination is mostly low-to moderate (modified contamination degree-mCd 1.36). The sediment contamination poses mostly a low ecological risk (RI 94.8). The sediment quality guideline quotient (SQG-Q 0.29) describes a moderate impact, while the probable effect concentration quotient (PEC-Q 0.16) confirms that there are no levels likely to affect the aquatic biota. In our study area, the main Branch of the Danube River and the Secondary Delta are the most affected by contamination, while the narrow, reed abundant channels as the preferred habitat of most aquatic organisms, have a low contamination level.     

Intranasal Delivery of Exendin-4 Confers Neuroprotective Effect Against Cerebral Ischemia in Mice

Exendin-4 is now considered as a promising drug for the treatment of cerebral ischemia. To determine the neuroprotective effects of intranasal exendin-4, C57BL/6J mice were intranasally administered with exendin-4 daily for 7 days before middle cerebral artery occlusion (MCAO) surgery. Intranasally administered exendin-4 produced higher brain concentrations and lower plasma concentrations when compared to identical doses administered interperitoneally. Neurological deficits and volume of infarcted lesions were analyzed 24 h after ischemia. Intranasal administration of exendin-4 exhibited significant neuroprotection in C57BL/6 mice subjected to MCAO by reducing neurological deficit scores and infarct volume. The neuroprotective effects of exendin-4 were blocked by the knockdown of GLP-1R with shRNA. However, exendin-4 has no impact on glucose and insulin levels which indicated that the neuroprotective effect was mediated by the activation of GLP-1R in the brain. Exendin-4 intranasal administration restored the balance between pro- and anti-apoptotic proteins and decreased the expression of Caspase-3. The anti-apoptotic effect was mediated by the cAMP/PKA and PI3K/Akt pathway. These findings provided evidence that exendin-4 intranasal administration exerted a neuroprotective effect mediated by an anti-apoptotic mechanism in MCAO mice and protected neurons against ischemic injury through the GLP-1R pathway in the brain. Intranasal delivery of exendin-4 might be a promising strategy for the treatment of ischemic stroke.     

Anti-Inflammatory and Antioxidant Mechanism of Tangeretin in Activated Microglia

Tangeretin, a flavonoid from citrus fruit peels, has been proven to play an important role in anti-inflammatory responses and neuroprotective effects in several disease models, but further study is necessary for elucidating the detailed mechanisms of these effects. In this study, we examined the anti-inflammatory effect of tangeretin in lipopolysaccharide (LPS)-stimulated microglia. We first observed that tangeretin inhibited LPS-induced production of nitric oxide, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β, as well as LPS-induced mRNA expression of inducible nitric oxide synthases and cytokines. Additionally, we found that the activities, mRNA levels, and protein levels of matrix metalloproteinase (MMP)-3 and MMP-8 were inhibited, while the expression of tissue inhibitor of metalloproteinase-2 was enhanced by tangeretin in LPS-stimulated microglia. Further mechanistic study showed that tangeretin suppressed LPS-induced phosphorylation of mitogen-activated protein kinases and Akt. Also, tangeretin inhibited nuclear factor-κB by upregulating sirtuin 1 and 5′-adenosine monophosphate-activated protein kinase. We further demonstrated the antioxidant effect of tangeretin by showing that tangeretin inhibited reactive oxygen species production and p47^phox phosphorylation, while enhancing the expression of heme oxygenase-1 and the DNA binding activity of nuclear factor-erythroid 2-related factor 2 to the antioxidant response element in LPS-stimulated microglia. Taken together, the results of the present study demonstrate that tangeretin possesses a potent anti-inflammatory and antioxidant effect in microglia.     

Assessment of DCE–MRI parameters for brain tumors through implementation of physiologically–based pharmacokinetic model approaches for Gd-DOTA

Dynamic-contrast enhanced magnetic resonance imaging (DCE–MRI) is used for detailed characterization of pathology of lesions sites, such as brain tumors, by quantitative analysis of tracer’s data through the use of pharmacokinetic (PK) models. A key component for PK models in DCE–MRI is the estimation of the concentration–time profile of the tracer in a nearby vessel, referred as Arterial Input Function (AIF). The aim of this work was to assess through full body physiologically-based pharmacokinetic (PBPK) model approaches the PK profile of gadoteric acid (Gd-DOTA) and explore potential application for parameter estimation in DCE-MRI based on PBPK-derived AIFs. The PBPK simulations were generated through Simcyp^® platform and the predicted PK parameters for Gd-DOTA were compared with available clinical data regarding healthy volunteers and renal impairment patients. The assessment of DCE-MRI parameters was implemented by utilizing similar virtual profiles based on gender, age and weight to clinical profiles of patients diagnosed with glioblastoma multiforme. The PBPK–derived AIFs were then used to compute DCE-MRI parameters through the Extended Tofts Model and compared with the corresponding ones derived from image-based AIF computation. The comparison involved: (i) image measured AIF of patients vs AIF of in silico profile, and, (ii) population average AIF vs in silico mean AIFs. The results indicate that PBPK–derived AIFs allowed the estimation of comparable imaging biomarkers with those calculated from typical DCE–MRI image analysis. The incorporation of PBPK models and potential utilization of in silico profiles to real patient data, can provide new perspectives in DCE–MRI parameter estimation and data analysis.