The Role of N-Methyl-D-Aspartate Receptor Neurotransmission and Precision Medicine in Behavioral and Psychological Symptoms of Dementia

While the world’s population is aging, the prevalence of dementia and the associated behavioral and psychological symptoms of dementia (BPSD) rises rapidly. BPSD are associated with worsening of cognitive function and poorer prognosis. No pharmacological treatment has been approved to be beneficial for BPSD to date. Dysfunction of the N-methyl-D-aspartate receptor (NMDAR)-related neurotransmission leads to cognitive impairment and behavioral changes, both of which are core symptoms of BPSD. Memantine, an NMDAR partial antagonist, is used to treat moderate to severe Alzheimer’s disease (AD). On the other hand, a D-amino acid oxidase inhibitor improved early-phase AD. Whether to enhance or to attenuate the NMDAR may depend on the phases of dementia. It will be valuable to develop biomarkers indicating the activity of NMDAR, particularly in BPSD. In addition, recent reports suggest that gender difference exists in the treatment of dementia. Selecting subpopulations of patients with BPSD who are prone to improvement with treatment would be important. We reviewed literatures regarding the treatment of BPSD, focusing on the NMDAR-related modulation and precision medicine. Future studies examining the NMDAR modulators with the aid of potential biomarkers to tailor the treatment for individualized patients with BPSD are warranted

Early Identification and Intervention of Schizophrenia: Insight From Hypotheses of Glutamate Dysfunction and Oxidative Stress

Schizophrenia is a severe mental disorder which leads to functional deterioration. Early detection and intervention are vital for better prognosis. However, the diagnosis of schizophrenia still depends on clinical observation to date. Without reliable biomarkers, schizophrenia is difficult to detect in its early phase. Further, there is no approved medication for prodromal schizophrenia because current antipsychotics fail to show satisfactory efficacy and safety. Therefore, to develop an effective early diagnostic and therapeutic approach for schizophrenia, especially in its prodromal phase, is crucial. Glutamate signaling dysfunction and dysregulation of oxidative stress have been considered to play important roles in schizophrenic prodrome. The N-methyl-D-aspartate receptor (NMDAR) is one of three types of ionotropic glutamate receptors. In this article, we reviewed literature regarding NMDAR hypofunction, oxidative stress, and the linkage between both in prodromal schizophrenia. The efficacy of NMDAR enhancers such as D-amino acid oxidase inhibitor was addressed. Finally, we highlighted potential biomarkers related to NMDAR and oxidative stress regulation, and therefore suggested the strategies of early detection and intervention of prodromal schizophrenia. Future larger-scale studies combining biomarkers and novel drug development for early psychosis are warranted

Benzoate, a D-Amino Acid Oxidase Inhibitor, for the Treatment of Early-Phase Alzheimer's Disease: A Randomized, Double-Blind, Placebo-Controlled Trial

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Combination of G72 Genetic Variation and G72 Protein Level to Detect Schizophrenia: Machine Learning Approaches

The D-amino acid oxidase activator (DAOA, also known as G72) gene is a strong schizophrenia susceptibility gene. Higher G72 protein levels have been implicated in patients with schizophrenia. The current study aimed to differentiate patients with schizophrenia from healthy individuals using G72 single nucleotide polymorphisms (SNPs) and G72 protein levels by leveraging computational artificial intelligence and machine learning tools. A total of 149 subjects with 89 patients with schizophrenia and 60 healthy controls were recruited. Two G72 genotypes (including rs1421292 and rs2391191) and G72 protein levels were measured with the peripheral blood. We utilized three machine learning algorithms (including logistic regression, naive Bayes, and C4.5 decision tree) to build the optimal predictive model for distinguishing schizophrenia patients from healthy controls. The naive Bayes model using two factors, including G72 rs1421292 and G72 protein, appeared to be the best model for disease susceptibility (sensitivity = 0.7969, specificity = 0.9372, area under the receiver operating characteristic curve (AUC) = 0.9356). However, a model integrating G72 rs1421292 only slightly increased the discriminative power than a model with G72 protein alone (sensitivity = 0.7941, specificity = 0.9503, AUC = 0.9324). Among the three models with G72 protein alone, the naive Bayes with G72 protein alone had the best specificity (0.9503), while logistic regression with G72 protein alone was the most sensitive (0.8765). The findings remained similar after adjusting for age and gender. This study suggests that G72 protein alone, without incorporating the two G72 SNPs, may have been suitable enough to identify schizophrenia patients. We also recommend applying both naive Bayes and logistic regression models for the best specificity and sensitivity, respectively. Larger-scale studies are warranted to confirm the findings

Hemispheric dispersion of radioactive plume laced with fission nuclides from the Fukushima nuclear event

Radioactivities of particulate 131I and 137Cs released from the Fukushima nuclear accident were monitored in a regional aerosol network including two high mountain sites (central Taiwan and Tibetan Plateau). The results were integrated with data measured elsewhere around the world, with special focus on the mid-latitudes. The hemispheric transport of the Fukushima radiation clouds (FRCs) by the westerlies took $18 days, displaying an exponential-like decrease eastward, with a dilution factor of at least five orders of magnitude following a full circuit around the globe. The initial two waves of FRCs may travel at different atitudes: the first one at$3–4 km, whereas the second one up to 5 km or more. 131I and 137Cs were fractionated during transport, with 137Cs concentrated in the shallower layer, susceptible to depositional removal, while 131I moving faster and higher. This accident may be exemplified to identify some atmospheric processes on the hemispheric scale

Relationship between overweight and obesity and insufficient micronutrient intake: a nationwide study in Taiwan

The aim of the present study is to examine whether overweight or obese people in Taiwan have an inadequate intake of selected micronutrients. A population-based study was conducted using data from the Nutrition and Health Survey in Taiwan (NAHSIT) 2013–2016. We evaluated fourteen nutrient intakes using the 24 h dietary recall method. The dietary reference intake (DRI) adherence was estimated by the prevalence of participants whose intake was lower than the recommended dietary allowance (RDA) or adequate intakes (AIs) for selected micronutrients. Body mass index (BMI) ≥ 27 kg/m2 and waist circumference (WC), with men having WC ≥ 90 cm or women having WC ≥ 80 cm, were defined as obesity. A total of 3075 participants aged 19 years and above were included. After adjusting for confounders, we found that obese women have a lower DRI adherence of vitamin C (odds ratio (OR) 0⋅73, 95 % confidence interval (CI) 0⋅56, 0⋅95) and magnesium (OR 0⋅72, 95 % CI 0⋅54, 0⋅95), compared with normal-weight women. Obese men have a higher DRI adherence of vitamin B3 (OR 1⋅70, 95 % CI 1⋅29, 2⋅23), iron (OR 1⋅46, 95 % CI 1⋅06, 2⋅00) and zinc (OR 1⋅41, 95 % CI 1⋅07, 1⋅85), compared with normal-weight men. Similar findings were found using WC to define obesity. We conclude that obese women may have insufficient intakes of vitamin A, vitamin C and magnesium