Welfare Genome Project: A Participatory Korean Personal Genome Project With Free Health Check-Up and Genetic Report Followed by Counseling.

The Welfare Genome Project (WGP) provided 1,000 healthy Korean volunteers with detailed genetic and health reports to test the social perception of integrating personal genetic and healthcare data at a large-scale. WGP was launched in 2016 in the Ulsan Metropolitan City as the first large-scale genome project with public participation in Korea. The project produced a set of genetic materials, genotype information, clinical data, and lifestyle survey answers from participants aged 20-96. As compensation, the participants received a free general health check-up on 110 clinical traits, accompanied by a genetic report of their genotypes followed by genetic counseling. In a follow-up survey, 91.0% of the participants indicated that their genetic reports motivated them to improve their health. Overall, WGP expanded not only the general awareness of genomics, DNA sequencing technologies, bioinformatics, and bioethics regulations among all the parties involved, but also the general public's understanding of how genome projects can indirectly benefit their health and lifestyle management. WGP established a data construction framework for not only scientific research but also the welfare of participants. In the future, the WGP framework can help lay the groundwork for a new personalized healthcare system that is seamlessly integrated with existing public medical infrastructure

Can Continuous Positive Airway Pressure Reduce the Risk of Stroke in Obstructive Sleep Apnea Patients? A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE:Obstructive sleep apnea (OSA) has been shown to increase the risk of stroke. Although continuous positive airway pressure (CPAP) is considered the treatment of choice for OSA, whether treating OSA with CPAP reduces the risk of stroke remains unclear. We aimed to evaluate the effects of CPAP on incidence of stroke in patients with OSA. MATERIALS AND METHODS:We conducted a systematic review and meta-analysis of all published studies that provided the number of incident strokes in OSA patients in light of their treatment status with CPAP. RESULTS:We identified 8 relevant studies: one randomized controlled study (RCT), 5 cohort studies, and 2 studies using administrative health data. The two overlapping cohort studies in women and the elderly and the 2 studies using administrative health data had analyzed the impact of CPAP on stroke apart from cardiac events, whereas the others had focused on the overall cardiovascular events. Based on a meta-analysis of the cohort studies, treatment with CPAP was associated with a lower incidence of stroke and cardiac events with relative risks of 0.27 [0.14-0.53], and 0.54 [0.38-0.75], respectively, although this could not be reproduced in the RCT and the studies using administrative data. CONCLUSIONS:Treating with CPAP in patients with OSA might decrease the risk of stroke, although there is some conflicting evidence. Such effect was more pronounced in stroke than in cardiac events. Future studies analyzing stroke apart from cardiac disease would be of interest

Evolution of the multi-tRNA synthetase complex and its role in cancer

© 2019 Hyeon et al. Aminoacyl-tRNA synthetases (ARSs) are enzymes that ligate their cognate amino acids to tRNAs for protein synthesis. However, recent studies have shown that their functions are expanded beyond protein synthesis through the interactions with diverse cellular factors. In this review, we discuss how ARSs have evolved to expand and control their functions by forming protein assemblies. We particularly focus on a macromolecular ARS complex in eukaryotes, named multi-tRNA synthetase complex (MSC), which is proposed to provide a channel through which tRNAs reach bound ARSs to receive their cognate amino acid and transit further to the translation machinery. Approximately half of the ARSs assemble into the MSC through cis-acting noncatalytic domains attached to their catalytic domains and trans-acting factors. Evolution of the MSC included its functional expansion, during which the MSC interaction network was augmented by additional cellular pathways present in higher eukaryotes. We also discuss MSC components that could be functionally involved in the pathophysiology of tumorigenesis. For example, the activities of some trans-acting factors have tumor-suppressing effects or maintain DNA integrity and are functionally compromised in cancer. On the basis of Gene Ontology analyses, we propose that the regulatory activities of the MSC-associated ARSs mainly converge on five biological processes, including mammalian target of rapamycin (mTOR) and DNA repair pathways. Future studies are needed to investigate how the MSC-associated and free-ARSs interact with each other and other factors in the control of multiple cellular pathways, and how aberrant or disrupted interactions in the MSC can cause diseas

PRISMA flow diagram.

<p>Flow diagram demonstrating the process of article selection for systematic review and meta-analysis.</p

Enrichment of infection-associated bacteria in the low biomass brain bacteriota of Alzheimer's disease patients.

Alzheimer's disease (AD) is a neurodegenerative disease accompanied by neuroimmune inflammation in the frontal cortex and hippocampus. Recently, the presence of bacteria in AD-affected brains has been documented, prompting speculation about their potential role in AD-associated neuroinflammation. However, the characterization of bacteriota in human brains affected by AD remains inconclusive. This study aimed to investigate potential associations between specific bacteria and AD pathology by examining brain tissues from AD-associated neurodegenerative regions (frontal cortex and hippocampus) and the non-AD-associated hypothalamus. Employing 16S rRNA gene sequencing, 30 postmortem brain tissue samples from four individuals with normal brain histology (N) and four AD patients were analyzed, along with three blank controls. A remarkably low biomass characterized the brain bacteriota, with their overall structures delineated primarily by brain regions rather than the presence of AD. While most analyzed parameters exhibited no significant distinction in the brain bacteriota between the N and AD groups, the unique detection of Cloacibacterium normanense in the AD-associated neurodegenerative regions stood out. Additionally, infection-associated bacteria, as opposed to periodontal pathogens, were notably enriched in AD brains. This study's findings provide valuable insights into potential link between bacterial infection and neuroinflammation in AD

Forest plots of the incidence of CVE.

<p>(A) Incidence of stroke. (B) Incidence of cardiac disease. (C) Incidence of overall CVE. Data were calculated by a random-effects model. The boxes represent standardized mean differences (SMDs), and lines depict 95% CIs. The vertical solid line represents no difference between CPAP and control. Values to the right of the solid line favor CPAP benefit. Pooled SMDs and 95% CIs are represented by the diamond shapes.</p

Forest plots of the mortality rates from CVE.

<p>(A) Mortality from stroke. (B) Mortality from cardiac disease. (C) Mortality from overall CVE.</p

Analysis of alpha- and beta-diversities in human brain tissues.

(A) OTUs of the HT, F, and HC, and those of N and AD are presented as box and whisker plots. (B) The Shannon indexes of the HT, F, and HC, and those of N and AD are presented as box and whisker plots (median: HT = 2.12, F = 1.34, HC = 2.64, N = 2.14, and AD = 2.03). (C) The multidimensional scaling (MDS) plot has been visualized using the Bray–Curtis and the significance of dissimilarities was examined by the permutational multivariate analysis of variance (HT vs F vs HC: R2 = 0.19, P = 0.001, N vs AD: R2 = 0.03, P = 0.647). (D) The Bray–Curtis distances of the N–N and AD–AD samples (Within), and those of N–AD samples (Between) were evaluated. (E) The Bray–Curtis distances of the (1)–(2) samples from the same donor (Within) and those of the samples from different donors (Between) were evaluated. The significance among the HT, F, and HC and between N and AD was examined by the Kruskal–Wallis test and Mann–Whitney U test, respectively.</p

Workflow of filtering steps of valid reads for microbiome analysis.

(A) Summary of filtering steps and the valid reads after each filter is presented. The 16S rRNA sequencing was performed on 30 human brain tissues from four normal individuals and four AD patients, and three negative controls. In the initial filtration phase, low-quality, off-target, and chimeric amplicons were eliminated from the dataset (Filter 1). Subsequently, species that displayed valid reads with ≤2 across all samples were excluded (Filter 2). The final filtration step involved the application of an exact binomial test to discern potential contaminants. Any identified potential contaminant was subsequently removed from the dataset (Filter 3) (B) The valid reads and (C) the copy number from the Filter 3 depending on groups are illustrated as box and whisker plots. The significance among the HT, F, and HC and between N and AD was examined by the Kruskal–Wallis test and Mann–Whitney U test, respectively.</p

Classification of species sources.

Alzheimer’s disease (AD) is a neurodegenerative disease accompanied by neuroimmune inflammation in the frontal cortex and hippocampus. Recently, the presence of bacteria in AD-affected brains has been documented, prompting speculation about their potential role in AD-associated neuroinflammation. However, the characterization of bacteriota in human brains affected by AD remains inconclusive. This study aimed to investigate potential associations between specific bacteria and AD pathology by examining brain tissues from AD-associated neurodegenerative regions (frontal cortex and hippocampus) and the non-AD-associated hypothalamus. Employing 16S rRNA gene sequencing, 30 postmortem brain tissue samples from four individuals with normal brain histology (N) and four AD patients were analyzed, along with three blank controls. A remarkably low biomass characterized the brain bacteriota, with their overall structures delineated primarily by brain regions rather than the presence of AD. While most analyzed parameters exhibited no significant distinction in the brain bacteriota between the N and AD groups, the unique detection of Cloacibacterium normanense in the AD-associated neurodegenerative regions stood out. Additionally, infection-associated bacteria, as opposed to periodontal pathogens, were notably enriched in AD brains. This study’s findings provide valuable insights into potential link between bacterial infection and neuroinflammation in AD.</div