In Vivo Reactive Astrocyte Imaging in Patients With Schizophrenia Using Fluorine 18-Labeled THK5351.

Importance: In vivo imaging studies of reactive astrocytes are crucial for understanding the pathophysiology of schizophrenia because astrocytes play a critical role in glutamate imbalance and neuroinflammation. Objective: To investigate in vivo reactive astrocytes in patients with schizophrenia associated with positive symptoms using monoamine oxidase B (MAO-B)-binding fluorine 18 ([18F])-labeled THK5351 positron emission tomography (PET). Design, Setting, and Participants: In this case-control study, data were collected from October 1, 2021, to January 31, 2023, from the internet advertisement for the healthy control group and from the outpatient clinics of Seoul National University Hospital in Seoul, South Korea, for the schizophrenia group. Participants included patients with schizophrenia and age- and sex-matched healthy control individuals. Main Outcomes and Measures: Standardized uptake value ratios (SUVrs) of [18F]THK5351 in the anterior cingulate cortex (ACC) and hippocampus as primary regions of interest (ROIs), with other limbic regions as secondary ROIs, and the correlation between altered SUVrs and Positive and Negative Syndrome Scale (PANSS) positive symptom scores. Results: A total of 68 participants (mean [SD] age, 32.0 [7.0] years; 41 men [60.3%]) included 33 patients with schizophrenia (mean [SD] age, 32.3 [6.3] years; 22 men [66.7%]) and 35 healthy controls (mean [SD] age, 31.8 [7.6] years; 19 men [54.3%]) who underwent [18F]THK5351 PET scanning. Patients with schizophrenia showed significantly higher SUVrs in the bilateral ACC (left, F = 5.767 [false discovery rate (FDR)-corrected P = .04]; right, F = 5.977 [FDR-corrected P = .04]) and left hippocampus (F = 4.834 [FDR-corrected P = .04]) than healthy controls. Trend-level group differences between the groups in the SUVrs were found in the secondary ROIs (eg, right parahippocampal gyrus, F = 3.387 [P = .07]). There were positive correlations between the SUVrs in the bilateral ACC and the PANSS positive symptom scores (left, r = 0.423 [FDR-corrected P = .03]; right, r = 0.406 [FDR-corrected P = .03]) in patients with schizophrenia. Conclusions and Relevance: This case-control study provides novel in vivo imaging evidence of reactive astrocyte involvement in the pathophysiology of schizophrenia. Reactive astrocytes in the ACC may be a future target for the treatment of symptoms of schizophrenia, especially positive symptoms.

Structural brain abnormalities and aggressive behaviour in schizophrenia: Mega-analysis of data from 2095 patients and 2861 healthy controls via the ENIGMA consortium.

Background: Schizophrenia is associated with an increased risk of aggressive behaviour, which may partly be explained by illness-related changes in brain structure. However, previous studies have been limited by group-level analyses, small and selective samples of inpatients and long time lags between exposure and outcome. Methods: This cross-sectional study pooled data from 20 sites participating in the international ENIGMA-Schizophrenia Working Group. Sites acquired T1-weighted and diffusion-weighted magnetic resonance imaging scans in a total of 2095 patients with schizophrenia and 2861 healthy controls. Measures of grey matter volume and white matter microstructural integrity were extracted from the scans using harmonised protocols. For each measure, normative modelling was used to calculate how much patients deviated (in z-scores) from healthy controls at the individual level. Ordinal regression models were used to estimate the associations of these deviations with concurrent aggressive behaviour (as odds ratios [ORs] with 99% confidence intervals [CIs]). Mediation analyses were performed for positive symptoms (i.e., delusions, hallucinations and disorganised thinking), impulse control and illness insight. Aggression and potential mediators were assessed with the Positive and Negative Syndrome Scale, Scale for the Assessment of Positive Symptoms or Brief Psychiatric Rating Scale. Results: Aggressive behaviour was significantly associated with reductions in total cortical volume (OR [99% CI] = 0.88 [0.78, 0.98], p = .003) and global white matter integrity (OR [99% CI] = 0.72 [0.59, 0.88], p = 3.50 × 10-5) and additional reductions in dorsolateral prefrontal cortex volume (OR [99% CI] = 0.85 [0.74, 0.97], p =.002), inferior parietal lobule volume (OR [99% CI] = 0.76 [0.66, 0.87], p = 2.20 × 10-7) and internal capsule integrity (OR [99% CI] = 0.76 [0.63, 0.92], p = 2.90 × 10-4). Except for inferior parietal lobule volume, these associations were largely mediated by increased severity of positive symptoms and reduced impulse control. Conclusions: This study provides evidence that the co-occurrence of positive symptoms, poor impulse control and aggressive behaviour in schizophrenia has a neurobiological basis, which may inform the development of therapeutic interventions.

Using brain structural neuroimaging measures to predict psychosis onset for individuals at clinical high-risk.

Machine learning approaches using structural magnetic resonance imaging (sMRI) can be informative for disease classification, although their ability to predict psychosis is largely unknown. We created a model with individuals at CHR who developed psychosis later (CHR-PS+) from healthy controls (HCs) that can differentiate each other. We also evaluated whether we could distinguish CHR-PS+ individuals from those who did not develop psychosis later (CHR-PS-) and those with uncertain follow-up status (CHR-UNK). T1-weighted structural brain MRI scans from 1165 individuals at CHR (CHR-PS+, n = 144; CHR-PS-, n = 793; and CHR-UNK, n = 228), and 1029 HCs, were obtained from 21 sites. We used ComBat to harmonize measures of subcortical volume, cortical thickness and surface area data and corrected for non-linear effects of age and sex using a general additive model. CHR-PS+ (n = 120) and HC (n = 799) data from 20 sites served as a training dataset, which we used to build a classifier. The remaining samples were used external validation datasets to evaluate classifier performance (test, independent confirmatory, and independent group [CHR-PS- and CHR-UNK] datasets). The accuracy of the classifier on the training and independent confirmatory datasets was 85% and 73% respectively. Regional cortical surface area measures-including those from the right superior frontal, right superior temporal, and bilateral insular cortices strongly contributed to classifying CHR-PS+ from HC. CHR-PS- and CHR-UNK individuals were more likely to be classified as HC compared to CHR-PS+ (classification rate to HC: CHR-PS+, 30%; CHR-PS-, 73%; CHR-UNK, 80%). We used multisite sMRI to train a classifier to predict psychosis onset in CHR individuals, and it showed promise predicting CHR-PS+ in an independent sample. The results suggest that when considering adolescent brain development, baseline MRI scans for CHR individuals may be helpful to identify their prognosis. Future prospective studies are required about whether the classifier could be actually helpful in the clinical settings.

Aberrant hyperfocusing in schizophrenia indicated by elevated theta phase-gamma amplitude coupling.

OBJECTIVE: We aimed to investigate electroencephalographic (EEG) markers of aberrant hyperfocusing, a novel framework of impaired selective attention, in schizophrenia patients by using theta phase-gamma amplitude coupling (TGC). METHODS: Fifty-four schizophrenia patients and 73 healthy controls (HCs) underwent EEG recording during an auditory oddball paradigm. For the standard and target conditions, TGC was calculated using the source signals from 25 brain regions of interest (ROIs) related to attention networks and sensory processing; TGC values were then compared across groups and conditions using two-way analysis of covariance. Correlations of altered TGC with performance on the Trail Making Test Parts A and B (TMT-A/B), were explored. RESULTS: Compared to HCs, schizophrenia patients showed elevated TGC in the left inferior frontal gyrus (IFG) and superior temporal gyrus in the standard condition but not in the target condition. Correlation analyses revealed that the TGC in the left IFG was positively correlated with the TMT-A/B completion times. CONCLUSIONS: Aberrant hyperfocusing, as reflected by elevated TGC in attention-related brain regions, was related to behavioral performance on the TMT-A/B in schizophrenia patients. SIGNIFICANCE: This study suggests that TGC is a electrophysiological marker for aberrant hyperfocusing of attentional processes that may result in cognitive impairments in schizophrenia patients.

Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis.

Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. Design, Setting, and Participants: This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. Main Outcomes and Measures: For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < -1.96) or supranormal (z > 1.96) scores. Results: Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the mean (SD) age was 22.32 (4.95) years. Individuals with CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z scores, and all ADS values. For any given region, the proportion of individuals with CHR-P who had infranormal or supranormal values was low (up to 153 individuals [<11.42%]) and similar to that of healthy individuals (<115 individuals [<9.30%]). Individuals with CHR-P who converted to a psychotic disorder had a higher percentage of infranormal values in temporal regions compared with those who did not convert (7.01% vs 1.38%) and healthy individuals (5.10% vs 0.89%). In the CHR-P group, only the ADS SA was associated with positive symptoms (ß = -0.08; 95% CI, -0.13 to -0.02; P = .02 for false discovery rate) and IQ (ß = 0.09; 95% CI, 0.02-0.15; P = .02 for false discovery rate). Conclusions and Relevance: In this case-control study, findings suggest that macroscale neuromorphometric measures may not provide an adequate explanation of psychosis risk.

Fronto-striato-thalamic circuit connectivity and neuromelanin in schizophrenia: an fMRI and neuromelanin-MRI study.

Changes in dopamine and fronto-striato-thalamic (FST) circuit functional connectivity are prominent in schizophrenia. Dopamine is thought to underlie connectivity changes, but experimental evidence for this hypothesis is lacking. Previous studies examined the association in some of the connections using positron emission tomography (PET) and functional MRI (fMRI); however, PET has disadvantages in scanning patients, such as invasiveness. Excessive dopamine induces neuromelanin (NM) accumulation, and NM-MRI is suggested as a noninvasive proxy measure of dopamine function. We aimed to investigate the association between NM and FST circuit connectivity at the network level in patients with schizophrenia. We analysed substantia nigra NM-MRI and resting-state fMRI data from 29 schizophrenia patients and 63 age- and sex-matched healthy controls (HCs). We identified the FST subnetwork with abnormal connectivity found in schizophrenia patients compared to that of HCs and investigated the relationship between constituting connectivity and NM-MRI signal. We found a higher NM signal (t = -2.12, p = 0.037) and a hypoconnected FST subnetwork (FWER-corrected p = 0.014) in schizophrenia patients than in HCs. In the hypoconnected subnetwork of schizophrenia patients, lower left supplementary motor area-left caudate connectivity was associated with a higher NM signal (ß = -0.38, p = 0.042). We demonstrated the association between NM and FST circuit connectivity. Considering that the NM-MRI signal reflects dopamine function, our results suggest that dopamine underlies changes in FST circuit connectivity, which supports the dopamine hypothesis. In addition, this study reveals implications for the future use of NM-MRI in investigations of the dopamine system.

Beyond verbal fluency in the verbal fluency task: semantic clustering as a predictor of remission in individuals at clinical high risk for psychosis.

BACKGROUND: There have been conflicting reports on whether conventional verbal fluency measures can predict the prognosis of individuals at clinical high risk (CHR) for psychosis. We aimed to investigate whether verbal fluency task measures that represent semantic processing more directly than conventional measures could be more reliable predictors of later remission in CHR individuals. METHODS: We recruited CHR individuals and healthy controls to participate in a baseline verbal fluency assessment. We identified semantic clusters within the verbal fluency task responses based on cosine similarity between consecutive words, calculated from the word embedding model. Binomial logistic regression was performed to test whether average semantic cluster size and number of words produced could be predictors of remission in CHR individuals. RESULTS: Our study sample included 96 CHR individuals and 178 healthy controls. According to clinical assessment at the last follow-up, 23 CHR individuals were classified as remitters and 73 as nonremitters, including 29 individuals who converted to psychosis. The CHR remitters showed larger average and maximum semantic cluster sizes than CHR nonremitters and healthy controls. Average semantic cluster size, but not the number of words, was a significant predictor of later remission in CHR individuals. LIMITATIONS: Our sample included only native Korean speakers. CONCLUSION: A verbal fluency task measure that more specifically represents semantic processing may be a better neurocognitive predictive marker for remission in CHR individuals than conventional verbal fluency measures. Our results provide an explanation for heterogeneous reports on whether verbal fluency can predict prognosis in CHR individuals and suggest that semantic processing is a putative cognitive predictor of their prognosis.

Intergenerational Transmission of Child Abuse Among Married Women in South Korea: A Multigroup Analysis of Empathetic Communication (TSL: Thanks, Sorry, and Love).

Intergenerational transmission of child abuse (hereinafter referred to as ITCA) has been continuously reported. Supportive relations with others have also been discussed as a protective factor to prevent this cycle. However, research has mainly investigated supportive adult and peer relationships formed in childhood, with little discussion of the impact of supportive partner relationships formed after becoming an adult. This study examined whether empathetic communication (hereinafter referred to as TSL: "Thanks, Sorry, and Love") attenuates the transmission of married women's child abuse experiences to subsequent generations mediated by intimate partner violence (hereinafter referred to as IPV). TSL is a communication strategy that promotes positive communication between intimate partners. We expected TSL to promote positive communication between couples through a process of self-transformation. Data from 1,122 married women were obtained from a nation-wide survey conducted in South Korea. All the survey respondents lived with partners and their own children simultaneously. For this study, structural equation model multigroup analysis was conducted to determine whether the pathways would be attenuated by TSL levels, showing that a high level of TSL communication attenuated the ITCA mediated by IPV. However, this process was maintained in the low-level TSL group. TSL is thus a protective factor against the ITCA. The findings suggest that healing processes can occur not only through childhood relationships but also through those formed after adulthood. Ultimately, to help victims recover, it is necessary to expand communication programs such as TSL that help victims learn how to express their feelings through healthy relationships with their partners.

Normative modeling of brain morphometry in Clinical High-Risk for Psychosis.

Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in the majority of individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high-risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. Design Setting and Participants: Clinical, IQ and FreeSurfer-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1,340 CHR-P individuals [47.09% female; mean age: 20.75 (4.74) years] and 1,237 healthy individuals [44.70% female; mean age: 22.32 (4.95) years] from 29 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. Main Outcomes and Measures: For each regional morphometric measure, z-scores were computed that index the degree of deviation from the normative means of that measure in a healthy reference population (N=37,407). Average deviation scores (ADS) for CT, SA, SV, and globally across all measures (G) were generated by averaging the respective regional z-scores. Regression analyses were used to quantify the association of deviation scores with clinical severity and cognition and two-proportion z-tests to identify case-control differences in the proportion of individuals with infranormal (z<-1.96) or supranormal (z>1.96) scores. Results: CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z-scores, and all ADS vales. The proportion of CHR-P individuals with infranormal or supranormal values in any metric was low (<12%) and similar to that of healthy individuals. CHR-P individuals who converted to psychosis compared to those who did not convert had a higher percentage of infranormal values in temporal regions (5-7% vs 0.9-1.4%). In the CHR-P group, only the ADSSA showed significant but weak associations (|ß|<0.09; PFDR<0.05) with positive symptoms and IQ. Conclusions and Relevance: The study findings challenge the usefulness of macroscale neuromorphometric measures as diagnostic biomarkers of psychosis risk and suggest that such measures do not provide an adequate explanation for psychosis risk.

Altered intrinsic cerebellar-cerebral functional connectivity is related to negative symptoms in patients with first-episode psychosis.

BACKGROUND: Negative symptoms in schizophrenia include cognitive and affective dysfunction, such as diminished expression and amotivation. Although the cerebellar posterior hemisphere and vermis are involved in cognitive and affective functioning, previous studies on the neural mechanism of negative symptoms have mostly been confined to the cerebral cortex. This study aimed to investigate whether resting-state cerebellar-cerebral functional connectivity (FC) is altered in first-episode psychosis (FEP) patients and whether this connectivity is related to negative symptoms. METHODS: Resting-state functional magnetic resonance images were obtained from 38 FEP patients and 100 healthy controls (HCs). Using the posterior hemisphere and vermis of the cerebellum as seeds, whole-brain FC was compared between FEP patients and HCs. As cerebellar-parietal cortex connectivity is associated with negative symptoms and sociocognitive dysfunctions in schizophrenia patients, its correlation with negative symptoms was explored in FEP patients. RESULTS: FEP patients showed hyperconnectivity between the cerebellum and bilateral frontal pole (FP), occipital pole, fusiform gyrus, right lingual gyrus, central opercular cortex, anterior middle temporal gyrus, precuneus, and subcallosal cortex. Hypoconnectivity was found between the cerebellum and left FP, right anterior supramarginal gyrus (aSMG), and cerebellum crus I. FC between the left crus II and right aSMG was negatively correlated with the severity of negative symptoms and diminished expression. CONCLUSIONS: Altered FC between the cerebellum and cerebral regions related to cognitive, affective, and sensory processing was found in FEP patients and was connected to negative symptoms. These results suggest that the cerebellum plays a role in the pathophysiology of negative symptoms in schizophrenia.

Volume deficits in hippocampal subfields in unaffected relatives of schizophrenia patients with high genetic loading but without any psychiatric symptoms.

BACKGROUND: Hippocampal volume changes have been reported in schizophrenia patients and their relatives and are proposed to contribute to the pathophysiology of schizophrenia. However, volume changes in the total hippocampus have not been consistently reported in relatives. The hippocampus consists of multiple subregions, and based on previous inconsistent results, subtle changes in specific subregions may occur in relatives. Here, we examined the subregion volumes in unaffected, high-functioning relatives (URs) without any psychiatric symptoms with high genetic loading with at least one first-degree relative diagnosed with schizophrenia and at least one or more other affected first- to third-degree relatives. METHODS: We acquired structural magnetic resonance imaging data from 50 URs, 101 first-episode psychosis (FEP) patients, and 101 healthy controls (HCs). The cornu ammonis (CA), dentate gyrus, and subiculum subfields were automatically segmented using FreeSurfer 7.1.0. Each subregion volume was compared across the groups. RESULTS: Compared with the HCs, the URs had a significant volume reduction in the left anterior CA (p = 0.039, Cohen's d = 0.480). In addition, the URs had a significantly larger right posterior subiculum (p = 0.001, Cohen's d = 0.541) than the FEP. CONCLUSIONS: The smaller left anterior CA in the URs may reflect their genetic vulnerability to schizophrenia and supports previous findings suggesting specific vulnerability in this region. The volume differences between the URs and FEP patients in the right posterior subiculum may suggest that a smaller volume in this region may reflect a risk for schizophrenia other than genetic vulnerability.

Epidemiology and prognostic indicators in laryngeal lymphoma: A population-based analysis.

OBJECTIVES/HYPOTHESIS: To characterize the epidemiology of primary laryngeal lymphoma and to determine the prognostic factors affecting survival in patients with this disease. STUDY DESIGN: A retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database, including cases from 1973 to 2014. METHODS: A population-based analysis was conducted with patients from more than 15 different geographic regions across the United States. Patients were chosen based on a diagnosis of lymphoma and a primary lymphoma site within the larynx. Two hundred cases were eligible based on the inclusion criteria, and characteristic as well as clinical variables were then extracted from the database and analyzed. Characteristic and clinical variables included age, race, sex, primary site of lymphoma involvement, general histology, specific histologic subtype, tumor grade, and Ann Arbor staging. Exposure variables that were analyzed included radiation therapy and chemotherapy. Overall survival (OS) and disease-specific survival (DSS) were the main outcomes calculated using multivariate analysis. RESULTS: A total of 200 cases of laryngeal lymphoma were identified. The mean age at diagnosis was 64.2 years. The cohort was composed of 53% males. B-cell non-Hodgkin's lymphoma (NHL) accounted for 74% of cases, whereas natural killer/T-cell NHL accounted for 10% of cases. A total of 53.1% of patients received radiation therapy, whereas 47.5% received chemotherapy. The median OS was 9.15 years and median DSS was 24.5 years. OS at 2, 5, and 10 years was 74%, 63%, and 44%, respectively. On multivariate analysis, older age, male sex, and advanced Ann Arbor staging were associated with worse OS, whereas only male sex and advanced Ann Arbor staging were associated with worse DSS (all P values < .05). Radiation and chemotherapy were not associated with improved survival. CONCLUSIONS: Female sex and lower Ann Arbor staging are independent positive prognostic indicators for survival, whereas other clinical variables such as grade and histology do not have an effect on survival. Radiation and chemotherapy do not appear to confer a mortality benefit in patients with primary laryngeal lymphoma, which may have implications on clinical decision making as well as patient education about disease prognosis. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:2044-2049, 2018.

Weight Change Is a Characteristic Non-Motor Symptom in Drug-Naïve Parkinson's Disease Patients with Non-Tremor Dominant Subtype: A Nation-Wide Observational Study.

Despite the clinical impact of non-motor symptoms (NMS) in Parkinson's disease (PD), the characteristic NMS in relation to the motor subtypes of PD is not well elucidated. In this study, we enrolled drug-naïve PD patients and compared NMS between PD subtypes. We enrolled 136 drug-naïve, early PD patients and 50 normal controls. All the enrolled PD patients were divided into tremor dominant (TD) and non-tremor dominant (NTD) subtypes. The Non-Motor Symptom Scale and scales for each NMS were completed. We compared NMS and the relationship of NMS with quality of life between normal controls and PD patients, and between the PD subtypes. Comparing with normal controls, PD patients complained of more NMS, especially mood/cognitive symptoms, gastrointestinal symptoms, unexplained pain, weight change, and change in taste or smell. Between the PD subtypes, the NTD subtype showed higher total NMS scale score and sub-score about weight change. Weight change was the characteristic NMS related to NTD subtype even after controlled other variables with logistic regression analysis. Even from the early stage, PD patients suffer from various NMS regardless of dopaminergic medication. Among the various NMS, weight change is the characteristic NMS associated with NTD subtype in PD patients.

Effects of granular activated carbon on methane removal performance and methanotrophic community of a lab-scale bioreactor.

Two identical lab-scale bioreactor systems were operated to examine the effects of granular activated carbon (GAC) on methane removal performance and methanotrophic community. Both bioreactor systems removed methane completely at a CH4 loading rate of 71.2 g-CH4·d(-1) for 17 days. However, the methane removal efficiency declined to 88% in the bioreactor without GAC, while the bioreactor amended with GAC showed greater methane removal efficiency of 97% at a CH4 loading rate of 107.5 g-CH4·d(-1). Although quantitative real-time PCR showed that methanotrophic populations were similar levels of 5-10 × 10(8) pmoA gene copy number·VSS(-1) in both systems, GAC addition changed the methanotrophic community composition of the bioreactor systems. Microarray assay revealed that GAC enhanced the type I methanotrophic genera including Methylobacter, Methylomicrobium, and Methylomonas of the system, which suggests that GAC probably provided a favorable environment for type I methanotrophs. These results indicated that GAC is a promising support material in bioreactor systems for CH4 mitigation.

Mild cognitive impairment due to alzheimer disease is less likely under the age of 65.

Patients with amnestic mild cognitive impairment (aMCI) are considered to have a high risk for Alzheimer dementia (AD). Even high positive predictive values, however, cannot be guaranteed even by tests with high sensitivity and specificity when disease prevalence is low. If we regard the clinical criteria for aMCI as a test for predicting aMCI due to AD, the positive predictive value of the criteria will be low by definition in young patients with aMCI (age below 65 years) because of the low prevalence of AD in this age group. To test this hypothesis, we compared CSF biomarkers for AD between young (age below 65 years) and old (age 65 years or older) age groups of normal cognition, aMCI, and AD of the Alzheimer's Disease Neuroimaging Initiative database. Using these biomarkers, we observed that the prevalence of aMCI due to AD differed significantly between the young and the old. For example, only 28.2% young aMCI, but 63.2% old aMCI, had abnormal CSF amyloid measures consistent with AD pathology. As posited, the presence of aMCI due to AD was lower in young aMCI than in old aMCI. Given that the likelihood of aMCI due to AD is reduced in younger subjects, more attention to and evaluation of alternative diagnoses need to be considered in this group.

Subcortical vascular dementia (SVaD) without hypertension (HTN) may be a unique subtype of vascular dementia (VaD).

Although HTN is the most important factor in the pathogenesis of SVaD, about 20% of patients with SVaD do not have HTN. We hypothesize that SVaD without HTN may have strong risk factors other than HTN, and the study on this group can elucidate the risk factors for SVaD. We included 332 patients with SVaD from the database of the Clinical Research Center for Dementia of South Korea (CREDOS) study. Among them, 26.2% of patients (87 out of 332) had no history of HTN. We analyzed the differences in risk factors, clinical features, and survival time of SVaD according to HTN. Contrary to our expectations, SVaD without HTN had less known vascular risk factors such as diabetes mellitus (DM), dyslipidemia, and obesity. In addition, SVaD without HTN had different clinical features including less depression, focal neurological signs or symptoms and more features of disinhibition. However, although SVaD without HTN had less known vascular risk factors that can shorten survival times, the survival times did not differ according to the presence of HTN. SVaD without HTN may be a unique subtype of SVaD and can be a target group for studies of unknown risk factors for SVaD.

Distribution of the corticobulbar tract in the internal capsule.

It is generally thought that the corticobulbar tract descends through the genu of the internal capsule (IC). There have been several reports that genu lesions cause bulbar symptoms such as facial palsies, dysarthria, and dysphagia. However, the precise location of the corticobulbar tract in the IC remains controversial. The purpose of our study is to assess whether the corticobulbar tract passes through the IC genu. We reviewed 26 patients with selective IC infarction and located the sites related to bulbar symptoms. In addition, using diffusion tensor imaging, we reconstructed tracts passing through the IC in ten subjects without cerebral infarction. Patients with genu infarction, which extended to more than half of the posterior limb of the IC, showed bulbar symptoms. However, patients with genu infarction, which was limited to the genu, did not have bulbar symptoms. In contrast, patients with lesions limited to the posterior limb may show bulbar symptoms. According to statistical maps of the region of interest, the lesions related to bulbar symptoms were localized to areas that were beyond the midpoint of the posterior limb of the IC. In diffusion tensor imaging of subjects without cerebral infarctions, the corticobulbar and corticospinal tracts did not pass through the IC genu. Our data provide evidence that the corticobulbar tract does not pass through the IC genu. The proposed location of the corticobulbar tract in the level of the IC lies beyond the midpoint of the posterior limb.

Effect of trichloroethylene and tetrachloroethylene on methane oxidation and community structure of methanotrophic consortium.

The methane oxidation rate and community structure of a methanotrophic consortium were analyzed to determine the effects of trichloroethylene (TCE) and tetrachloroethylene (PCE) on methane oxidation. The maximum methane oxidation rate (Vmax ) of the consortium was 326.8 µmol·g-dry biomass(-1)·h(-1), and it had a half-saturation constant (Km ) of 143.8 µM. The addition of TCE or PCE resulted in decreased methane oxidation rates, which were decreased from 101.73 to 5.47-24.64 µmol·g-dry biomass(-1)·h(-1) with an increase in the TCE-to-methane ratio, and to 61.95-67.43 µmol·g-dry biomass(-1)·h(-1) with an increase in the PCE-to-methane ratio. TCE and PCE were non-competitive inhibitors for methane oxidation, and their inhibition constants (Ki ) were 33.4 and 132.0 µM, respectively. When the methanotrophic community was analyzed based on pmoA using quantitative real-time PCR (qRT-PCR), the pmoA gene copy numbers were shown to decrease from 7.3 ± 0.7 × 10(8) to 2.1-5.0 × 10(7) pmoA gene copy number · g-dry biomass(-1) with an increase in the TCE-to-methane ratio and to 2.5-7.0 × 10(7) pmoA gene copy number · g-dry biomass(-1) with an increase in the PCE-to-methane ratio. Community analysis by microarray demonstrated that Methylocystis (type II methanotrophs) were the most abundant in the methanotrophic community composition in the presence of TCE. These results suggest that toxic effects caused by TCE and PCE change not only methane oxidation rates but also the community structure of the methanotrophic consortium.