Transcriptomics in Alzheimer's Disease: Aspects and Challenges.

Alzheimer's disease (AD) is the most common cause of dementia. Although the heritability of AD is high, the knowledge of the disease-associated genes, their expression, and their disease-related pathways remain limited. Hence, finding the association between gene dysfunctions and pathological mechanisms, such as neuronal transports, APP processing, calcium homeostasis, and impairment in mitochondria, should be crucial. Emerging studies have revealed that changes in gene expression and gene regulation may have a strong impact on neurodegeneration. The mRNA-transcription factor interactions, non-coding RNAs, alternative splicing, or copy number variants could also play a role in disease onset. These facts suggest that understanding the impact of transcriptomes in AD may improve the disease diagnosis and also the therapies. In this review, we highlight recent transcriptome investigations in multifactorial AD, with emphasis on the insights emerging at their interface.

Clinical Trial of Erythropoietin in Young Children With Cerebral Palsy.

This study was conducted to assess the safety and efficacy of recombinant human erythropoietin in young children with cerebral palsy aged between 6 months and 3 years. All participants received subcutaneous recombinant human erythropoietin and 8 weeks of rehabilitation therapy. Adverse events, changes of vital signs, and hematologic tests were monitored up to 8 weeks postinjection. Functional measures of development at 4 and 8 weeks postinjection were compared with baseline values, and improvements were compared with those of an age-matched historical control group. Nine participants completed the trial from June 2012 to February 2015. No adverse events were related to recombinant human erythropoietin. Erythropoiesis was noted, although within normal range. Functional improvements were observed in all participants (P < .05) and increases in motor function were higher in recombinant human erythropoietin group than the control group. Accordingly, recombinant human erythropoietin administration was safe without any significant adverse events and improved the functional outcomes in young children with cerebral palsy.

Alternative application of Tau protein in Creutzfeldt-Jakob disease diagnosis: Improvement for weakly positive 14-3-3 protein in the laboratory.

The 14-3-3 protein has been used as a biomarker for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). However, weakly positive 14-3-3 leads to false positive results and an incorrect diagnosis. We attempted to use quantitative data for tau protein to provide an accurate diagnosis based on weak 14-3-3 protein. Sixty-two patients with sCJD, including pathologically confirmed, clinically definite, and probable cases, and 89 non-CJD patients were investigated based on a Korean population. Among them, 20 sCJD and 14 non-CJD showed weakly positive 14-3-3. The total tau (t-tau) and phosphorylated tau (p-tau) protein levels were measured by ELISA, and the p-tau to t-tau ratio (p/t ratio) was calculated. The combined use of the 14-3-3 protein assay, t-tau levels, and p/t ratio improved the specificity of diagnosis compared with the use of the 14-3-3 protein assay alone (47% for 14-3-3 alone; 85.94% for 14-3-3 combined with t-tau; 90.62% for 14-3-3 combined with the p/t ratio). In addition, 18 of 20 sCJD and 12 of 14 non-CJD who were weakly positive for 14-3-3 were positive for the p/t ratio and negative for the p/t ratio, respectively. When used in combination with the 14-3-3 protein, the tau protein is useful as a biomarker for the precise diagnosis of sCJD.

Involvement of Immune Responses in the Efficacy of Cord Blood Cell Therapy for Cerebral Palsy.

This study evaluated the efficacy of umbilical cord blood (UCB) cell for patients with cerebral palsy (CP) in a randomized, placebo-controlled, double-blind trial and also assessed factors and mechanisms related to the efficacy. Thirty-six children (ages 6 months to 20 years old) with CP were enrolled and treated with UCB or a placebo. Muscle strength and gross motor function were evaluated at baseline and 1, 3, and 6 months after treatment. Along with function measurements, each subject underwent (18)F-fluorodeoxyglucose positron emission tomography at baseline and 2 weeks after treatment. Cytokine and receptor levels were quantitated in serial blood samples. The UCB group showed greater improvements in muscle strength than the controls at 1 (0.94 vs. -0.35, respectively) and 3 months (2.71 vs. 0.65) after treatment (Ps<0.05). The UCB group also showed greater improvements in gross motor performance than the control group at 6 months (8.54 vs. 2.60) after treatment (P<0.01). Additionally, positron emission tomography scans revealed decreased periventricular inflammation in patients administered UCB, compared with those treated with a placebo. Correlating with enhanced gross motor function, elevations in plasma pentraxin 3 and interleukin-8 levels were observed for up to 12 days after treatment in the UCB group. Meanwhile, increases in blood cells expressing Toll-like receptor 4 were noted at 1 day after treatment in the UCB group, and they were correlated with increased muscle strength at 3 months post-treatment. In this trial, treatment with UCB alone improved motor outcomes and induced systemic immune reactions and anti-inflammatory changes in the brain. Generally, motor outcomes were positively correlated with the number of UCB cells administered: a higher number of cells resulted in better outcomes. Nevertheless, future trials are needed to confirm the long-term efficacy of UCB therapy, as the follow-up duration of the present trial was short.

Evaluation of five rapid diagnostic kits for influenza A/B virus.

Influenza viruses cause seasonal epidemics associated with high morbidity and mortality. However, even during periods of epidemic prevalence, clinical diagnoses are problematic. Rapid diagnostic tests for the detection of pandemic influenza A/B virus are valuable for their ease of use. Many rapid influenza diagnostic kits were introduced recently in the Republic of Korea (ROK), including Directizen EZ Flu A and B (Becton Dickinson, Sparks, USA), Binax Now Influenza A/B antigen kit (Binax, Portland, USA), Genedia influenza Ag (Green Cross, Yongin, ROK), Humasis Influenza A/B antigen test (Humasis, Anyang, ROK), and SD Bioline rapid influenza kit (Standard Diagnostics, Yongin, ROK). The objective of this study was to evaluate the performance of these five rapid diagnostic kits. The results were compared with those of viral culture and reverse transcription (RT)-PCR. A total of 253 nasopharyngeal swabs were analyzed from 253 patients (influenza A, n=67; B, n=86; negative samples, n=100). The specimens were tested immediately by conventional influenza virus culture and RT-PCR, stored at -80°C, and tested using five rapid test kits. The performance of the five rapid tests kits varied with sensitivities between 71.0 and 82.1% and between 37.2 and 47.7% for detecting influenza A and B, respectively. For influenza A, the sensitivities of the Directizen EZ Flu A and B, Binax Now Influenza A/B antigen kit, Genedia influenza Ag, Humasis Influenza A/B antigen test, and SD Bioline rapid influenza kits were 82.1%, 71.0%, 76.1%, 79.1%, and 82.1%, respectively; those for influenza B were 40.7%, 37.2%, 40.7%, 41.8%, and 47.7%, respectively. The specificity of all rapid tests was 100%. Commercial influenza antigen detection assays are useful tools for the rapid diagnosis of influenza. However, confirmatory testing is always recommended.