Choroid Plexus Volume and Permeability at Brain MRI within the Alzheimer Disease Clinical Spectrum.

Background Mounting evidence suggests that the choroid plexus (CP) plays an important role in the pathophysiology of Alzheimer disease (AD), but its imaging profile in cognitive impairment remains unclear. Purpose To evaluate CP volume, permeability, and susceptibility by using MRI in patients at various stages of cognitive impairment. Materials and Methods This retrospective study evaluated patients with cognitive symptoms who underwent 3.0-T MRI of the brain, including dynamic contrast-enhanced (DCE) imaging and quantitative susceptibility mapping (QSM), between January 2013 and May 2020. CP volume was automatically segmented using three-dimensional T1-weighted sequences; the volume transfer constant (ie, Ktrans) and fractional plasma volume (ie, Vp) were determined using DCE MRI, and susceptibility was assessed using QSM. The effects of CP volume, expressed as the ratio to intracranial volume, on cognition were evaluated using multivariable linear regression adjusted for age, sex, education, apolipoprotein E ε4 allele status, and volumetric measures. Results A total of 532 patients with cognitive symptoms (mean age, 72 years ± 9 [SD]; 388 women) were included: 78 with subjective cognitive impairment (SCI), 158 with early mild cognitive impairment (MCI), 149 with late MCI, and 147 with AD. Among these, 132 patients underwent DCE MRI and QSM. CP volume was greater in patients at more severe stages (ratio of intracranial volume × 103: 0.9 ± 0.3 for SCI, 1.0 ± 0.3 for early MCI, 1.1 ± 0.3 for late MCI, and 1.3 ± 0.4 for AD; P < .001). Lower Ktrans (r = -0.19; P = .03) and Vp (r = -0.20; P = .02) were negatively associated with CP volume; susceptibility was not (r = 0.15; P = .10). CP volume was negatively associated with memory (B = -0.67; standard error of the mean [SEM], 0.21; P = .01), executive function (B = -0.90; SEM, 0.31; P = .01), and global cognition (B = -0.82; SEM, 0.32; P = .01). Conclusion Among patients with cognitive symptoms, larger choroid plexus volume was associated with severity of cognitive impairment in the Alzheimer disease spectrum. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Chiang in this issue.

Magnetic susceptibility in the deep gray matter may be modulated by apolipoprotein E4 and age with regional predilections: a quantitative susceptibility mapping study.

PURPOSE: To examine the relationship between apolipoprotein E gene (APOE) mutation status and iron accumulation in the deep gray matter of subjects with cognitive symptoms using quantitative susceptibility mapping (QSM). METHODS: A total of 105 patients with cognitive symptoms were enrolled. QSM data were generated from 3D gradient-echo data using an STI Suite algorithm. A region of interest-based analysis with QSM was performed in the deep gray matter. Differences between APOE4 carriers and non-carriers were assessed by analysis of covariance. Multiple regression analysis was performed to identify the factors associated with magnetic susceptibility. RESULTS: Clinical characters such as age, education, MMSE, vascular risk burden, and systolic blood pressure differ between APOE4 carrier and non-carrier groups. The APOE4 carrier group had higher magnetic susceptibility values than the non-carrier group, with significant differences in the caudate (p = 0.004), putamen (p < 0.0001), and globus pallidus (p < 0.0001) which imply higher iron accumulation. In a multiple regression analysis, APOE4 status was found to be a predictor of magnetic susceptibility value in the globus pallidus (p = 0.03); age for magnetic susceptibility value in the caudate nucleus (p = 0.0064); and age and hippocampal atrophy for magnetic susceptibility value in the putamen (p < 0.05). CONCLUSION: Our study demonstrates that magnetic susceptibility in globus pallidus is related to APOE4 status while those of caudate and putamen are related to other factors including age. It suggests that brain iron accumulation in the deep gray matter is modulated by APOE4 and age with differential regional predilection.

Male-Specific and Somatic Coliphage Profiles from Major Aquaculture Areas in Republic of Korea.

Human and animal feces are important sources of various types of microbial contamination in water. Especially, enteric viruses, the major agents of waterborne infection, can attain long-term survival in water environments due to their strong resistance to various environmental factors including pH, salinity, and temperature. Coliphages are promising viral indicators for fecal contamination in water environments. Here, we investigated the seasonal and spatial distribution of male-specific and somatic coliphages in surface water and seawater at three major aquaculture areas, including Goseong Bay, Aphae Island, and Gomso Bay, in Republic of Korea over a period of 1 year. We selected 6 surface water and 14 seawater sampling sites for each study area and collected a total of 480 water samples from March 2014 to February 2015. Overall, surface water samples contained higher occurrences of coliphages than seawater samples. The high coliphage concentrations were detected in spring (March to May 2014). The differences in geographical features and patterns in land usage of the three aquaculture areas may have affected the coliphage concentration and occurrence. Moreover, environmental factors such as cumulative precipitation were strongly correlated with coliphage concentrations. Therefore, we suggest that further longitudinal studies on coliphage concentrations and distributions should be performed to support the application of coliphages in tracking fecal contamination in water.

Use of coliphages to investigate norovirus contamination in a shellfish growing area in Republic of Korea.

A number of severe norovirus outbreaks due to the consumption of contaminated shellfish have been reported recently. In this study, we evaluated the distribution of coliphage densities to determine their efficacy as fecal indicators of enteric viruses, including noroviruses, in water samples collected from a shellfish growing area in Republic of Korea over a period of approximately 1 year. Male-specific and somatic coliphages in water samples were analyzed using the single agar layer method, and norovirus genogroups I and II, which infect mainly humans, were analyzed using duplex reverse transcription quantitative PCR. Male-specific and somatic coliphages were detected widely throughout the study area. Several environmental parameters, including salinity, precipitation, temperature, and wind speed were significantly correlated with coliphage concentrations (P < 0.05). Moreover, the concentrations of male-specific coliphages were positively correlated with the presence of human noroviruses (r = 0.443; P < 0.01). The geospatial analysis with coliphage concentrations using a geographic information system revealed that densely populated residential areas were the major source of fecal contamination. Our results indicate that coliphage monitoring in water could be a useful approach to prevent norovirus contamination in shellfish.

Host-Specific Bacteroides Markers-Based Microbial Source Tracking in Aquaculture Areas.

Various waterborne pathogens originate from human or animal feces and may cause severe gastroenteric outbreaks. Bacteroides spp. that exhibit strong host- or group-specificities are promising markers for identifying fecal sources and their origins. In the present study, 240 water samples were collected from two major aquaculture areas in Republic of Korea over a period of approximately 1 year, and the concentrations and occurrences of four host-specific Bacteroides markers (human, poultry, pig, and ruminant) were evaluated in the study areas. Host-specific Bacteroides markers were detected widely in the study areas, among which the poultry-specific Bacteroides marker was detected at the highest concentration (1.0-1.2 log10 copies L-1). During the sampling period, high concentrations of host-specific Bacteroides markers were detected between September and December 2015. The host-specific Bacteroides marker-combined geospatial map revealed the up-to-downstream gradient of fecal contamination, as well as the effects of land-use patterns on host-specific Bacteroides marker concentrations. In contrast to traditional bacterial indicators, the human-specific Bacteroides marker correlated with human specific pathogens, such as noroviruses (r=0.337; P<0.001). The present results indicate that host-specific Bacteroides genetic markers with an advanced geospatial analysis are useful for tracking fecal sources and associated pathogens in aquaculture areas.

Re-emergence of a GII.4 Norovirus Sydney 2012 Variant Equipped with GII.P16 RdRp and Its Predominance over Novel Variants of GII.17 in South Korea in 2016.

Noroviruses are major causative pathogen of nonbacterial acute gastroenteritis worldwide. Of the seven genogroups of noroviruses suggested recently, genogroup II genotype 4 (GII.4) had been the most common genotype identified in hospitalized patients in the last few decades. However, since the latter half of 2014, new variants of GII.17 have been reported as the main causes of outbreaks over GII.4 in East Asia and have also occurred in America and Europe. In this study, we monitored norovirus GII in coastal streams at South Gyeongsang province and South Jeolla province of South Korea from March 2015 to May 2016. Norovirus GII.17 capsid sequences were predominantly detected until September 2015 in water samples. However, we found that the number of positive cases of the norovirus GII.4 Sydney 2012 capsid sequence has been increasing since December 2015, overtaking that of GII.17 in 2016. The RdRp genotype of this predominant GII.4 variant in 2016 was identified as GII.P16. The emergence and predominance of the GII.4 pandemic capsid sequence harboring a different RdRp genotype suggested the potential for a future pandemic.

Identification of novel therapeutic target genes in acquired lapatinib-resistant breast cancer by integrative meta-analysis.

Acquired resistance to lapatinib is a highly problematic clinical barrier that has to be overcome for a successful cancer treatment. Despite efforts to determine the mechanisms underlying acquired lapatinib resistance (ALR), no definitive genetic factors have been reported to be solely responsible for the acquired resistance in breast cancer. Therefore, we performed a cross-platform meta-analysis of three publically available microarray datasets related to breast cancer with ALR, using the R-based RankProd package. From the meta-analysis, we were able to identify a total of 990 differentially expressed genes (DEGs, 406 upregulated, 584 downregulated) that are potentially associated with ALR. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs showed that "response to organic substance" and "p53 signaling pathway" may be largely involved in ALR process. Of these, many of the top 50 upregulated and downregulated DEGs were found in oncogenesis of various tumors and cancers. For the top 50 DEGs, we constructed the gene coexpression and protein-protein interaction networks from a huge database of well-known molecular interactions. By integrative analysis of two systemic networks, we condensed the total number of DEGs to six common genes (LGALS1, PRSS23, PTRF, FHL2, TOB1, and SOCS2). Furthermore, these genes were confirmed in functional module eigens obtained from the weighted gene correlation network analysis of total DEGs in the microarray datasets ("GSE16179" and "GSE52707"). Our integrative meta-analysis could provide a comprehensive perspective into complex mechanisms underlying ALR in breast cancer and a theoretical support for further chemotherapeutic studies.