Various probiotic strains have been reported to affect emotional behavior. However, the underlying mechanisms by which specific probiotic strains change brain function are not clearly understood. Here, we report that extracellular vesicles derived from Lactobacillus paracasei (Lpc-EV) have an ability to produce genome-wide changes against glucocorticoid (GC)-induced transcriptional responses in HT22 hippocampal neuronal cells. Genome-wide analysis using microarray assay followed by Rank-Rank Hypergeometric Overlap (RRHO) method leads to identify the top 20%-ranked 1,754 genes up- or down-regulated following GC treatment and their altered expressions are reversed by Lpc-EV in HT22 cells. Serial k-means clustering combined with Gene Ontology enrichment analyses indicate that the identified genes can be grouped into multiple functional clusters that contain functional modules of “responses to stress or steroid hormones”, “histone modification”, and “regulating MAPK signaling pathways”. While all the selected genes respond to GC and Lpc-EV at certain levels, the present study focuses on the clusters that contain Mkp-1, Fkbp5, and Mecp2, the genes characterized to respond to GC and Lpc-EV in opposite directions in HT22 cells. A translational study indicates that the expression levels of Mkp-1, Fkbp5, and Mecp2 are changed in the hippocampus of mice exposed to chronic stress in the same directions as those following GC treatment in HT22 cells, whereas Lpc-EV treatment restored stress-induced changes of those factors, and alleviated stress-induced depressive-like behavior. These results suggest that Lpc-EV cargo contains bioactive components that directly induce genome-wide transcriptional responses against GC-induced transcriptional and behavioral changes.

Purpose: This study aimed to investigate whether a deep learning model for automated detection of unruptured intracranial aneurysms on time-of-flight (TOF) magnetic resonance angiography (MRA) can achieve a target diagnostic performance comparable to that of human radiologists for approval from the Korean Ministry of Food and Drug Safety as an artificial intelligence-applied software. Materials and Methods: In this single-center, retrospective, confirmatory clinical trial, the diagnostic performance of the model was evaluated in a predetermined test set. After sample size estimation, the test set consisted of 135 aneurysm-containing examinations with 168 intracranial aneurysms and 197 aneurysm-free examinations. The target sensitivity and specificity were set as 87% and 92%, respectively. The patient-wise sensitivity and specificity of the model were analyzed. Moreover, the lesion-wise sensitivity and false-positive detection rate per case were also investigated. Results: The sensitivity and specificity of the model were 91.11% [95% confidence interval (CI): 84.99, 95.32] and 93.91% (95% CI:89.60, 96.81), respectively, which met the target performance values. The lesion-wise sensitivity was 92.26%. The overall falsepositive detection rate per case was 0.123. Of the 168 aneurysms, 13 aneurysms from 12 examinations were missed by the model. Conclusion The present deep learning model for automated detection of unruptured intracranial aneurysms on TOF MRA achieved the target diagnostic performance comparable to that of human radiologists. With high standalone performance, this model may be useful for accurate and efficient diagnosis of intracranial aneurysm.

Purpose: This study aimed to investigate whether a deep learning model for automated detection of unruptured intracranial aneurysms on time-of-flight (TOF) magnetic resonance angiography (MRA) can achieve a target diagnostic performance comparable to that of human radiologists for approval from the Korean Ministry of Food and Drug Safety as an artificial intelligence-applied software. Materials and Methods: In this single-center, retrospective, confirmatory clinical trial, the diagnostic performance of the model was evaluated in a predetermined test set. After sample size estimation, the test set consisted of 135 aneurysm-containing examinations with 168 intracranial aneurysms and 197 aneurysm-free examinations. The target sensitivity and specificity were set as 87% and 92%, respectively. The patient-wise sensitivity and specificity of the model were analyzed. Moreover, the lesion-wise sensitivity and false-positive detection rate per case were also investigated. Results: The sensitivity and specificity of the model were 91.11% [95% confidence interval (CI): 84.99, 95.32] and 93.91% (95% CI:89.60, 96.81), respectively, which met the target performance values. The lesion-wise sensitivity was 92.26%. The overall falsepositive detection rate per case was 0.123. Of the 168 aneurysms, 13 aneurysms from 12 examinations were missed by the model. Conclusion The present deep learning model for automated detection of unruptured intracranial aneurysms on TOF MRA achieved the target diagnostic performance comparable to that of human radiologists. With high standalone performance, this model may be useful for accurate and efficient diagnosis of intracranial aneurysm.

Emerging evidence has suggested that the gut microbiota contribute to brain dysfunction, including pathological symptoms of Alzheimer disease (AD). Microbiota secrete membrane vesicles, also called extracellular vesicles (EVs), which contain bacterial genomic DNA fragments and other molecules and are distributed throughout the host body, including blood. In the present study, we investigated whether bacteria-derived EVs in blood are useful for metagenome analysis in an AD mouse model. Sequence readings of variable regions of 16S rRNA genes prepared from blood EVs in Tg-APP/PS1 mice allowed us to identify over 3,200 operational taxonomic units corresponding to gut microbiota reported in previous studies. Further analysis revealed a distinctive microbiota landscape in Tg-APP/PS1 mice, with a dramatic alteration in specific microbiota at all taxonomy levels examined. Specifically, at the phylum level, the occupancy of p_Firmicutes increased, while the occupancy of p_Proteobacteria and p_Bacteroidetes moderately decreased in Tg-APP/PS1 mice. At the genus level, the occupancy of g_Aerococcus, g_Jeotgalicoccus, g_Blautia, g_Pseudomonas and unclassified members of f_Clostridiale and f_Ruminococcaceae increased, while the occupancy of g_Lactobacillus, unclassified members of f_S24-7, and g_Corynebacterium decreased in Tg-APP/PS1 mice. A number of genus members were detected in Tg-APP/PS1 mice, but not in wild-type mice, while other genus members were detected in wild-type mice, but lost in Tg-APP/PS1 mice. The results of the present study suggest that the bodily microbiota profile is altered in Tg-APP/PS1 mice, and that blood EVs are useful for the metagenome analysis of bodily microbiota in AD.
Alzheimer Disease* ; Animals ; Brain ; Classification ; DNA ; Extracellular Vesicles ; Gastrointestinal Microbiome ; Genes, rRNA ; Membranes* ; Metagenome* ; Metagenomics ; Mice* ; Microbiota* ; Reading

PURPOSE: Infants with Alagille syndrome (AGS) are occasionally misdiagnosed as biliary atresia and subsequently undergo Kasai operation. The purpose of this study was to investigate the outcome of patients with AGS who had previously received Kasai operation during infancy. METHODS: This retrospective study was conducted at the Department of Pediatrics, Samsung Medical Center. We compared the prognosis and mortality between those who had undergone Kasai operation during infancy (Kasai group) and those who had not (non-Kasai group). RESULTS: Among the 15 children with AGS, five had received Kasai operation, while 10 had not. All subjects in the Kasai group revealed neonatal cholestasis, while 70% of the non-Kasai group showed neonatal cholestasis. Liver transplantation was performed in 100% (5/5) among the Kasai group, and 20.0% (2/10) among the non-Kasai group (p=0.007). Mortality was observed in 60.0% (3/5) among the Kasai group, and 10.0% (1/10) among the non-Kasai group (p=0.077). CONCLUSION: Although overall mortality rate did not significantly differ between the two groups, the proportion of patients receiving liver transplantation was significantly higher in the non-Kasai group. The relatively worse outcome in AGS patients who had received Kasai operation may be due to the unfavorable influences of Kasai operation on the clinical course of AGS, or maybe due to neonatal cholestasis, irrespective of the Kasai operation.
Alagille Syndrome* ; Biliary Atresia ; Child ; Cholestasis ; Humans ; Infant ; Liver Transplantation ; Mortality ; Pediatrics ; Prognosis ; Retrospective Studies

BACKGROUND/AIMS: Liver stiffness (LS) as assessed by transient elastography (TE) can change longitudinally in patients with chronic hepatitis B (CHB). The aim of this study was to identify the factors that improve LS. METHODS: Between April 2007 and December 2012, 151 patients with CHB who underwent two TE procedures with an interval of about 2 years were enrolled. Ninety-six of the 151 patients were treated with nucleos(t)ide analogues [the antiviral therapy (+) group], while the remaining 55 patients were not [the antiviral therapy (-) group]. The two groups of patients were stratified according to whether they exhibited an improvement or a deterioration in LS during the study period (defined as an LS change of < or =0 or >0 kPa, respectively, over a 1-year period), and their data were compared. RESULTS: No differences were observed between the antiviral therapy (+) and (-) groups with respect to either their clinical characteristics or their initial LS. The observed LS improvement was significantly greater in the antiviral therapy (+) group than in the antiviral therapy (-) group (-3.0 vs. 0.98 kPa, P=0.011). In the antiviral therapy (+) group, the initial LS was higher in the LS improvement group (n=63) than in the LS deterioration group (n=33; 7.9 vs. 4.8 kPa, P<0.001). However, there were no differences in any other clinical characteristic. In the antiviral therapy (-) group, the initial LS was also higher in the LS improvement group (n=29) than in the LS deterioration group (n=26; 8.3 vs. 6.5 kPa, P=0.021), with no differences in any other clinical characteristic. CONCLUSIONS: A higher initial LS was the only factor associated with LS improvement in patients with CHB in this study.
Adult ; Aged ; Alanine Transaminase/blood ; Antiviral Agents/therapeutic use ; DNA, Viral/blood ; Elasticity Imaging Techniques ; Female ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/drug therapy/pathology/*ultrasonography ; Humans ; Logistic Models ; Longitudinal Studies ; Male ; Middle Aged

Animal models of depression are used to study pathophysiology of depression and to advance therapeutic strategies. Stress-induced depression models in rodents are widely used. However, amenable behavioral criteria and experimental procedures that are suitable for animal models have not been established. Given that depression is clinically diagnosed by multiple symptomatic criteria and stress effects are imposed to the brain non-specifically in stress-induced depression models, analyses of depression states in rodents using multiple symptomatic criteria may provide more power than any methods relying on a single symptomatic criterion. To address this, C57BL/6 inbred mice were restrained for 2 h daily for 14 d, and depression states of individual mice were assessed using the U-field test, behavioral assessment developed to measure animal's sociability, and the tail suspension test and/or forced swim test, which are the typical methods that measure psychomotor withdrawal states. Although the majority of these mice showed severe depressive behaviors in both tests, a significant proportion of them, which were all inbred mice and received the same amount of restraints, expressed differential depression states in the sociability test and psychomotor withdrawal tests. To easily read-out differential depression states of individuals in two different tests, a standard method and basic parameters required to construct two-way behavior matrix were introduced. The utility and features of this two-way behavior analysis method for studies of different depressive states of individuals were discussed.
Animals ; Brain ; Depression* ; Hindlimb Suspension ; Mice ; Models, Animal ; Rodentia*

BACKGROUND: This study was designed to find appropriate lubricant for streamed lined liner of pharyngeal airway(TM) (SLIPA(TM)). We evaluated the incidence of sore throat, nausea, vomiting, hoarseness, paresthesia and blood stain after using saline, water soluble gel and 2% lidocaine gel as a SLIPA(TM) lublicant. METHODS: One hundred twenty three patients scheduled for minor surgery to whom the SLIPA(TM) was considered suitable were randomly allocated to one of three groups which receive normal saline, water soluble gel or 2% lidocaine gel as a SLIPA(TM) lublicant. Patients were interviewed at recovery room, post operation 6-12 hour, post operation 18-24 hour about sore throat and other complications. RESULTS: There were no statistical difference in sore throat and blood stain among three groups. Also there were no statistical differences in hoarseness, nausea, vomiting. The incidence of paresthesia in 2% lidocaine gel group was significantly higher than those of the other two groups immediately after operation, but it was resolved after leaving the recovery room. CONCLUSIONS: Our results suggest that normal saline, water soluble gel and 2% lidocaine gel are all available as a SLIPA(TM) lubricant. Size of SLIPA(TM), insertion technique and difficulty of insertion should be further investigated as the main causes of a sore throat and other complications which can occur after the insertion of SLIPA(TM).
Blood Stains ; Hoarseness ; Humans ; Incidence ; Lidocaine* ; Nausea ; Paresthesia ; Pharyngitis ; Recovery Room ; Rivers ; Surgical Procedures, Minor ; Vomiting

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) may be one of the important causes of cryptogenic hepatocellular carcinoma (HCC). The aim of this study was to evaluate whether patients with cryptogenic HCC share clinical features similar to that of NAFLD. METHODS: Cryptogenic HCC was defined as HCC that occurs in patients with the following conditions: HBsAg(-), anti-HCV(-), and alcohol ingestion of less than 20 g/day. All patients diagnosed with cryptogenic HCC from 2005 to 2012 (cryptogenic HCC group), and all patients diagnosed with HBV associated HCC between 2008 and 2012 (HBV-HCC group) were enrolled in the present study. Clinical features, BMI, lipid profiles, presence of diabetes mellitus, hypertension, and metabolic syndrome were compared between the two groups. RESULTS: Cryptogenic HCC group was composed of 35 patients (19 males and 16 females) with a mean age of 70+/-11 years. HBV-HCC group was composed of 406 patients (318 males and 88 females) with a mean age of 56+/-7 years. Patients in the cryptogenic HCC group were older (p=0.001) and female dominant (p=0.042) than those in the HBV-HCC group. There were no differences in the laboratory test results including lipid profiles and Child-Turcotte-Pugh class between the two groups. Patients in the cryptogenic HCC group had higher prevalence of diabetes (37% vs. 17%, p=0.015), hypertension (49% vs. 27%, p=0.051), metabolic syndrome (37% vs. 16%, p=0.001), and higher BMI (25.3 kg/m2 vs. 24.1 kg/m2, p=0.042) than those in the HBV-HCC group. The tumor stage was more advanced (stage III and IV) at diagnosis in the cryptogenic HCC group than in the HBV-HCC group (60% vs. 37%, p=0.007). CONCLUSIONS: Cryptogenic HCC has clinical features similar to that of NAFLD and is diagnosed at a more advanced tumor stage.
Age Factors ; Aged ; Body Mass Index ; Carcinoma, Hepatocellular/*diagnosis/etiology/pathology ; Diabetes Complications ; Diabetes Mellitus/pathology ; Female ; Hepatitis B/complications ; Humans ; Hypertension/complications ; Lipids/blood ; Liver Neoplasms/*diagnosis/etiology/pathology ; Male ; Metabolic Syndrome X/complications ; Middle Aged ; Neoplasm Staging ; Non-alcoholic Fatty Liver Disease/*diagnosis/pathology ; Risk Factors ; Severity of Illness Index ; Sex Factors

BACKGROUND: The diagnostic criteria of complex regional pain syndrome (CRPS) have mainly focused on dichotomous (yes/no) categorization, which makes it difficult to compare the inter-patient's condition and to evaluate the intra-patient's subtle severity over the course of time. To overcome this limitation, many efforts have been made to create laboratory methods or scoring systems to reflect the severity of CRPS; measurement of the skin temperature asymmetry is one of the former, and the CRPS severity score (CSS) is one of the latter. However, there has been no study on the correlations among the CSS, temperature asymmetry and subjective pain score. The purpose of this study was to evaluate whether there is any correlation between the CSS, skin temperature asymmetry and subjective pain score. METHODS: Patients affected with CRPS in a unilateral limb were included in this study. After making a diagnosis of CRPS according to the Budapest criteria, the CSS and skin temperature difference between the affected and unaffected limb (DeltaT) was measured in each patient. Finally, we conducted a correlation analysis among the CSS, DeltaT and visual analogue scale (VAS) score of the patients. RESULTS: A total of 42 patients were included in this study. There was no significant correlation between the DeltaT and VAS score (Spearman's rho = 0.066, P = 0.677). Also, the CSS and VAS score showed no significant correlation (Spearman's rho = 0.163, P = 0.303). CONCLUSIONS: The DeltaT and CSS do not seem to reflect the degree of subjective pain in CRPS patients.
Diagnosis ; Extremities ; Humans ; Pain Measurement ; Severity of Illness Index ; Skin Temperature*