Pharmacological Intervention Targeting FAF1 Restores Autophagic Flux for α-Synuclein Degradation in the Brain of a Parkinson's Disease Mouse Model.

α-Synuclein accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD). Previously, we reported that Fas-associated factor 1 (FAF1), which plays a role in PD pathogenesis, potentiates α-synuclein accumulation through autophagy impairment in dopaminergic neurons. In this study, we show that KM-819, a FAF1-targeting compound, which has completed phase I clinical trials, interferes with α-synuclein accumulation in the mouse brain, as well as in human neuronal cells (SH-SY5Ys). KM-819 suppressed the accumulation of monomeric, oligomeric, and aggregated forms of α-synuclein in neuronal cells. Furthermore, KM-819 restored the turnover rate of α-synuclein in FAF1-overexpressing SH-SY5Y cells, implicating KM-819-mediated reconstitution of the α-synuclein degradative pathway. In addition, KM-819 reconstituted autophagic flux in FAF1-transfected SH-SY5Y cells, also suppressing α-synuclein-induced mitochondrial dysfunction. Moreover, oral administration of KM-819 also interfered with α-synuclein accumulation in the midbrain of mice overexpressing FAF1 via an adeno-associated virus system. Consistently, KM-819 reduced α-synuclein accumulation in both the hippocampus and the midbrain of human A53T α-synuclein transgenic mice. Collectively, these data imply that KM-819 may have therapeutic potential for patients with PD.

Electron transport and photosynthetic performance in Fragaria × ananassa Duch. acclimated to the solar spectrum modified by a spectrum conversion film.

Functional films have been used in greenhouses to improve the light environment for plant growth. Among them, a spectrum conversion film converting the green light of incident sunlight into red light has been reported to increase the crop productivity. However, the results are not always consistent, and the reasons for the improvement are not fully understood. The objectives of this study were to reveal the cumulative effects of a green-to-red spectrum conversion film (SCF) on the electron transport and photosynthetic performance of Fragaria × ananassa Duch. The photosynthetic efficiency, leaf optical properties, chlorophyll content, chlorophyll fluorescence, growth, and fruit qualities when the plant was grown under a transparent polyethylene film (PE) and SCF were evaluated. The sunlight modified by SCF did not change the leaf optical properties and chlorophyll content but significantly increased the chlorophyll fluorescence parameters related to reduction end electron acceptors at PSI acceptor side and the efficiency of electron transport. Without an increase in nonphotochemical quenching, the effective quantum yields of PSII and PSI of leaves grown under SCF were significantly higher than those parameters when grown under PE. Forty eight days after transplanting, the photosynthetic efficiency and photosynthetic rates of leaves and whole plants increased significantly under SCF compared to PE. The vegetative growth was not affected by SCF, but the fruit weight, sweetness, acidity, and firmness under SCF were significantly improved. These results indicated that sunlight modified by SCF stimulates electron flow and improves photosynthetic capacity and fruit quality of Fragaria × ananassa Duch.

Fas-associated factor 1 induces the accumulation of α-synuclein through autophagic suppression in dopaminergic neurons.

Impairment of protein clearance mechanisms leads to α-synuclein accumulation in dopaminergic neurons, contributing to the pathogenesis of Parkinson's disease (PD). Based on the finding that Fas-associated factor 1 (FAF1), a positive modulator of PD, colocalizes with α-synuclein in PD patient brains, we investigated the existence of pathological interplay between FAF1 and α-synuclein. Monomeric and high-molecular-weight forms of α-synuclein were increased in FAF1-overexpressing SH-SY5Y cells. In particular, α-synuclein turnover was accelerated by genetic depletion of FAF1 in SH-SY5Y cells. Therefore, we questioned whether FAF1 is involved in the α-synuclein clearance process. Autophagy inhibitors, but not proteasome inhibitors, restored concurrent attenuation of α-synuclein expression by FAF1 depletion in SH-SY5Y cells. Moreover, we found alterations in autophagy markers in SH-SY5Y cells caused by FAF1 overexpression, indicating that FAF1 disturbed α-synuclein clearance through the autophagy-lysosome pathway. Indeed, FAF1 activated the mammalian target of rapamycin (mTOR) pathway, subsequently suppressing autophagosome formation. Consistently, α-synuclein-mediated mitochondrial dysfunction was observed in FAF1-overexpressing SH-SY5Y cells. Furthermore, FAF1 overexpression using stereotaxic injection of adeno-associated virus led to α-synuclein accumulation and autophagy dysregulation in the PD model mice. Taken together, our results reveal a novel role for FAF1: that of a negative regulator of autophagic α-synuclein clearance.

Neurorestorative Effects of a Novel Fas-Associated Factor 1 Inhibitor in the MPTP Model: An [18F]FE-PE2I Positron Emission Tomography Analysis Study.

Fas-associated factor 1 (FAF1), a Fas-binding protein, is implicated in neuronal cell death in Parkinson's disease (PD). We examined the effects of a novel FAF1 inhibitor, KM-819, in dopaminergic neurons in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model using [18F]FE-PE2I positron emission tomography (PET). The MPTP model was generated with subacute MPTP treatment (20 mg/kg/day, i.p.) for 5 consecutive days in C57bl/6J mice. This study included three groups: the control group (treatment with saline only), the MPTP model group with KM-819 treatment (20 mg/kg/day p.o.) for 6 days, and the MPTP model group without KM-819 treatment. [18F]FE-PE2I PET studies were conducted in the same animals before and after MPTP with or without KM-819 treatment to monitor changes in striatal dopamine transporter activity indicated by non-displaceable binding potential (BPND) of [18F]FE-PE2I, and the expression levels of tyrosine hydroxylase were assessed using immunohistochemistry before and after KM-819 treatment. After MPTP injection, decreased striatal BPND was observed in the MPTP model group compared with the control group. Striatal BPND increased in the MPTP model group with KM-819 treatment, but not in the MPTP model group without KM-819 treatment. The tyrosine hydroxylase expression levels also significantly increased in the MPTP model group with KM-819 treatment compared with the control group. This study indicates that inhibition of the Fas-mediated cell death pathway by KM-819 has neurorestorative effects in striatal dopamine neurons in the MPTP model. Further studies would be needed to investigate the potential of KM-819 as a therapeutic drug for PD treatment.

A first-in-human study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of KM-819 (FAS-associated factor 1 inhibitor), a drug for Parkinson's disease, in healthy volunteers.

BACKGROUND: KM-819 is a novel FAS-associated factor 1 (FAF1) inhibitor, and a neuroprotective agent, under clinical development for the treatment of Parkinson's disease as a disease-modifying drug. METHODS: This first-in-human, single and multiple ascending dose study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of KM-819 in healthy volunteers. Additionally, the effect of age on safety and pharmacokinetics were assessed. The starting dose was determined considering the no observed adverse effect level based on preclinical studies, and the dose escalations in subsequent cohorts were decided based on safety, tolerability, and pharmacokinetic data from previous dose cohorts. RESULTS: After a single dose, the KM-819 plasma exposure showed a less than dose-proportional increase across a dose range of 10-400 mg. After repeated dosing, KM-819 plasma exposure increased in an approximately dose-proportional manner across the evaluated dose range (30-400 mg once daily for 7 days). The mean elimination half-life was 1.8 to 4.8 h with the lower KM-819 doses (≤30 mg), which increased to around 9 h with the higher doses (100-400 mg). When administered to the elderly population, KM-819 plasma exposure increased to 102% after a 200 mg once-daily dosing for 7 days. No clear treatment-related effects on the estimated pharmacodynamic variables were observed. Single or multiple doses of KM-819 were generally well tolerated. CONCLUSION: The data from this study can be used to guide rational drug dosing and choose therapeutic regimens in subsequent clinical studies.

Novel Trajectories for Identifying Asthma Phenotypes: A Longitudinal Study in Korean Asthma Cohort, COREA.

BACKGROUND: Unbiased cluster analysis has identified several asthma phenotypes. However, these phenotypes did not consistently predict disease prognosis and reflect temporal variability in airway inflammation. OBJECTIVE: We aimed to identify longitudinal trajectories in terms of pulmonary function parameters and investigated whether the trajectories are associated with prognosis. METHODS: Data were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA). Three-year pulmonary function test results were used to apply finite mixture models for group-based trajectory in 486 patients with eligible data set. RESULTS: Two main sets of longitudinal trajectories were identified in terms of FEV1% predicted, and FEV1 variability. In the 4 trajectories determined with FEV1% predicted, the pulmonary function showed a consistent course in 4 stratified levels during 3 years of follow-up, which was associated with unexpected hospital visits and the use of steroid bursts due to exacerbation. The variability in pulmonary function showed 3 different patterns, and we found that higher blood and sputum eosinophil levels were associated with the higher variability in pulmonary function and more exacerbations. CONCLUSIONS: Trajectory analysis is a novel method that provides longitudinal asthma phenotypes and aids in prediction of future risk of exacerbation. Further analysis is needed to validate the usefulness of these trajectories in an independent population.

Aggregation induced emission of diketopyrrolopyrrole (DPP) derivatives for highly fluorescent red films.

A large number of diketopyrrolopyrrole (DPP) compounds showing aggregation induced emission (AIE) have been reported in the past few years. However, although DPP compounds exhibited AIE and excellent luminescence properties, their luminescence properties in solid or film states were not much focused on. Here we synthesized and characterized a series of DPP compounds with triphenylamine (TPA) moieties to investigate the AIE properties in the solid film state depending on the functional groups (TPA, BTPA, and MTPA) attached to the TPA moieties. T2 and D2 thin films showed excellent fluorescence quantum yields of 31% and 26%, respectively, compared to an M2 thin film (9%). The restriction of an intramolecular rotation process could inhibit the aggregation induced quenching process and play a key role in achieving highly fluorescent molecules in the solid state.

Prediction of emergence agitation using withdrawal reaction following rocuronium injection in preschool-aged patients undergoing inguinal herniorrhaphy: a preliminary exploratory observational trial.

PURPOSE: The development of emergence agitation (EA) is associated with several factors including age, preoperative anxiety, postoperative pain, anesthesia method, and surgery type. No studies have investigated whether the withdrawal reaction following rocuronium injection can predict the occurrence of EA. Therefore, we investigated this relationship in preschool-aged children undergoing inguinal herniorrhaphy, and which grade of withdrawal reaction is appropriate for identifying patients at risk of experiencing EA. METHODS: A total of 40 patients were enrolled in this study. During anesthesia induction, the withdrawal reaction after loss of consciousness following rocuronium injection was assessed using a 4-point scale. After surgery, EA was assessed using the Watcha scale. RESULTS: There was a correlation between withdrawal reaction and EA on admission to the postanesthesia care unit (PACU). Patients with a severe withdrawal reaction (grade 3) showed a significantly higher incidence of severe EA requiring medication on admission to the PACU. CONCLUSION: The findings of this preliminary exploratory observational study suggest that it is possible for withdrawal movement following rocuronium injection during anesthesia induction to reflect pain sensitivity of pediatric patients, which in turn may be useful in identifying those at risk of severe EA on admission to the PACU among preschool children undergoing inguinal herniorrhaphy. Further studies with a larger sample size are required to validate these findings. The exact correlation between pain reaction following rocuronium injection and postoperative pain or pain-related phenomenon should be elucidated.

Simple modification of basic dyes with bulky &symmetric WCAs for improving their solubilities in organic solvents without color change.

A simple and easy solubility enhancement of basic dyes was performed with bulky and symmetric weakly coordinating anions (WCAs). The WCAs decreased the ionic character of the dyes by broadening the partial charge distribution and causing a screening effect on the ionic bonding. This new modification with WCAs has advantages in that it has no influence on the optical properties of the dyes. The solubilities of unmodified and modified dyes were tested in several organic solvents. X-ray powder diffraction patterns of the dyes were measured. Color films were prepared with the dyes and their color loci were analyzed to evaluate the optical properties. By the modification with WCAs, commercial basic dyes showed sufficient solubilities for be applied to various applications while preserving their superior optical properties.

Identification of Korean-specific SNP markers from whole-exome sequencing data.

Analysis of large numbers of single-nucleotide polymorphisms (SNPs) can increase individual discrimination power, and, particularly, it can supply important evidence for kinship or ethnic identification. We identified 300 Korean-specific SNPs from 306 Korean whole-exome sequencing (WES) data. Functionally significant SNPs (variants in splicing site, missense, nonsense, and exonic indels) were filtered out from the variant pool, and SNPs with minor allele frequencies (MAFs) of <0.3 in the 1000 Genomes (1000G) database but >0.3 in the Korean population were selected. Genotypes obtained from WES were confirmed by the Sanger sequencing method. The identified markers were evenly distributed throughout the autosomal chromosomes. All the SNPs were in the Hardy-Weinberg equilibrium with a mean MAF of 0.415 (0.161 in 1000G). The mean heterozygosities were 0.476 (observed) and 0.470 (experimental). The combined power of discrimination was very high. Korean MAFs in most SNPs were similar to those for the Chinese and Japanese populations, but were significantly higher than those for several other ethnic populations. These selected SNPs will be used to develop forensic markers and are expected to be widely used for additional individual identification, ethnic discrimination, and linkage analysis for kinship tests.

Centroid method: an alternative method of determining coronal curvature in scoliosis. A comparative study versus Cobb method in the degenerative spine.

BACKGROUND CONTEXT: Although the Cobb method is considered the gold standard, the centroid method may offer a reasonable alternative in adult scoliosis because it has better inter- and intraobserver reliabilities in adolescent scoliosis. PURPOSE: To compare the reliabilities of the Cobb and the centroid methods for measuring coronal curvature in degenerative scoliosis in older patients. STUDY DESIGN: Observational study involving three examiners. PATIENT SAMPLE: Sixty whole spine posteroanterior (PA) radiographs were collected. OUTCOME MEASURES: Data were analyzed to determine inter- and intraobserver reliabilities. METHODS: Sixty whole spine PA radiographs of patients older than 60 years were collected to compare the reliabilities of the centroid and the Cobb methods for measuring coronal curvature in degenerative scoliosis. Three examiners using both methods independently measured radiographs twice. Data were analyzed to determine inter- and intraobserver reliabilities. RESULTS: Intraobserver comparisons of all the 60 radiographs revealed that inter- and intraclass correlation coefficients (ICCs) of the Cobb and the centroid methods were both excellent (greater than 0.979 vs. greater than 0.918), and mean absolute differences (MADs) were similar (less than 1.58 vs. less than 2.02). In interobserver comparisons, ICCs of the Cobb method were higher than that of the centroid method (greater than 0.922 vs. greater than 0.799), and the MADs of the Cobb method were lower than that of the centroid method (less than 2.91 vs. less than 4.84). Comparisons of radiographs subdivided by severity showed that the ICCs of the Cobb and the centroid methods were both excellent (greater than 0.819 vs. greater than 0.801), and their MADs were similar (less than 2.29 vs. less than 2.53) for intraobserver comparisons. Interobserver comparisons showed that ICCs and MADs were dependent on the severity of coronal curvature, and the ICCs of the Cobb method (greater than 0.698) were greater than that of the centroid method (greater than 0.507). Furthermore, MAD values for the Cobb method were lower than that for the centroid method (less than 3.59 vs. less than 6.07). Moreover, these results are contradictory to the previous study, which showed the higher reliability of the centroid method in measures of adolescent scoliosis. CONCLUSIONS: In the present study, the reliability of the centroid method was found to be more susceptible to the severity of disease in older patients, despite its demonstrated greater reliability in adolescent scoliosis. Our findings show that the selective use of these two methods in old and young patients can increase the reliabilities of measurements made.

Gender differences of the morphology of the distal femur and proximal tibia in a Korean population.

PURPOSE: We conducted this study to determine whether the sizes of distal femurs and proximal tibiae in Korean men and women are different, and to assess suitability of the sizes of prostheses currently used in Korea. MATERIALS AND METHODS: We performed morphological analysis of proximal tibia and distal femur on 115 patients (56 male, 59 female) using MRI to investigate a gender difference. Tibial mediolateral dimension (tMAP), tibial medial anteroposterior dimension (tMAP), tibial lateral anteroposterior dimension (tLAP) femoral mediolateral dimension (fML), femoral medial anteroposterior dimension (fMAP), and femoral lateral anteroposterior dimension (fLAP) were measured. The ratio of tMAP and tLAP to tML (plateau aspect ratio, tAP/tML×100%), and that of fMAP and fLAP to fML (condylar aspect ratio, fAP/fML×100%) were calculated. The measurements were compared with the similar dimensions of four total knee implants currently used. RESULTS: The tML and tAP lengths showed a significant gender difference (P<0.05). The plateau aspect ratio (tMAP/tML) revealed a significant difference between male (0.74±0.05) and female (0.68±0.04, P<0.05). For morphotype of distal femur, males were found to have significantly large values (P<0.05) in the parameters, except for fLAP. With regards to the ratio of the ML width to the AP length, the women showed a narrower ML width than the men. Both genders were distributed within the range of the dimensions of the prostheses currently used prostheses. CONCLUSIONS: Korean population revealed that women have smaller dimensions than male counterparts. In both genders, a relatively small size of prostheses matches distal femur and proximal tibia better among the implants currently used in Korea.

A comparative analysis of 4 curvature measurement methods in early-onset scoliosis.

STUDY DESIGN: Observational study with 3 examiners. OBJECTIVE: The aim of this study was to enhance the reproducibility and reliability of coronal curvature measurements in early-onset scoliosis. SUMMARY OF BACKGROUND DATA: Previous reports show high variability of the Cobb method, especially on the measurement of the immature spine. METHODS: A total of 115 whole-spine posteroanterior radiographs were collected to compare the reliability of the Cobb, lateral tangent, pedicle, and centroid methods in early-onset scoliosis. Radiographs were measured twice by each of the 3 examiners using the 4 measurement methods. Statistical analysis was performed to determine the inter- and intraobserver reliability. RESULTS: In this study, total inter- and intraobserver inter- and intraclass correlation coefficients (ICCs) in 115 radiographs were excellent in all methods (ICCs >0.961). However, mean absolute differences (MADs) in the lateral tangent method were less than 3.78°, which was higher than other methods (MADs <2.95°). In analysis of different severity groups (<15°, 15°-30°, and >30°), total inter- and intraobserver ICCs gradually increased with increasing the severity of the deformity, whereas MADs of each severity group were similar despite their increased measurement scale. Particularly, interobserver ICCs and MADs of lateral tangent method were more than 0.474 and less than 3.76° with poor reliability, which showed high variability in the less deformed spine group (<15°). However, intraobserver ICCs and MADs of pedicle method were more than 0.853 and less than 2.61°, interobserver ICCs and MADs were more than 0.729 and less than 2.86° with excellent reliability, which showed constantly high reliability regardless of coronal curvature severity. CONCLUSION: In this study, the pedicle method showed constantly higher ICCs and lower MAD values in the early-onset scoliosis regardless of severity. However, the other 3 methods showed lower ICCs and higher MAD values, which showed lowest reliability in the lateral tangent method. For improved treatment of early-onset scoliosis, we recommend the pedicle method for measuring curvature regardless of severity.

Hemiarthroplasty in a patient with pigmented villonodular synovitis of the shoulder.

We report the 2-year follow-up results of a hemiarthroplasty in a 29-year-old patient with pigmented villonodular synovitis (PVNS) with extra-articular extension and severe bony destruction. The patient presented with diffuse pain and swelling of the right shoulder for several years. Radiographs showed severe osteolytic lesions in the humeral head and neck, greater tuberosity, and a small osteolytic lesion in the glenoid neck area. Further examination with magnetic resonance imaging of the shoulder joint showed a large, lobulated soft tissue mass extending from the subdeltoid area to the chest wall invading the adjacent bony structures. The operative findings included a large, multilobulated, yellowish-brown mass extending from the subdeltoid area to the axillary pouch, subacromial space, and thoracic wall. The mass invaded the anatomical neck area of the humeral head and caused a fracture of the humeral head. We observed a complete rupture of the long head of the biceps tendon, supraspinatus tendon, and infraspinatus tendon, but the subscapularis tendon was partially ruptured. We performed the complete excision and cemented hemiarthroplasty. At 2-year follow-up, no signs of local recurrence were present. The patient had no significant pain and achieved a good functional result.To the best of our knowledge, 1 report with shoulder hemiarthroplasty in PVNS of the shoulder has been published in the English literature. For PVNS of the shoulder with a large extra-articular extension and bony destruction, shoulder arthroplasty with total synovectomy produces the lowest recurrence rates because of better access and excision to the posterior location of the PVNS lesion.

Secondary omental infarction related to open and laparoscopic-assisted distal gastrectomy: report of two cases.

Omental infarction occurring after open and laparoscopic-assisted distal gastrectomy with partial omentectomy for gastric cancer was a very rare disease in the past, but its incidence has increased as more partial omentectomies are now being performed. But there are few case reports or radiologic studies on its increasing incidence. It is necessary to differentiate omental infarction from carcinomatosis peritonei, since both have similar imaging findings. In this report, we describe two cases of omental infarction; each occurred after open and laparoscopic-assisted distal gastrectomy in early gastric cancer patients. Partial omentectomy was performed in both cases. Omental infarction following distal gastrectomy with partial omentectomy can be discriminated from carcinomatosis peritonei by comparing with different initial and follow up CT findings.

Bone quality and growth characteristics of growth plates following limb transplantation between animals of different ages--results of an experimental study in male syngeneic rats.

INTRODUCTION: The purpose of this study was to identify graft osteoporosis post transplantation by micro-CT analysis, and the growth potential of growth plates in the transplanted limb. METHODS: Ten juvenile to juvenile and five juvenile to adult hind limb transplants were performed in male syngeneic Lewis rats. Upper tibial bone density in isochronograft and heterochronograft limbs was measured by 3D micro-CT and compared with that of the opposite non-operated limbs. RESULTS: We observed inferior bone quality (p < 0.05) in heterochronografts compared to isochronografts. After transplantation, isochronografts did not exhibit increases in tibial lengths compared to opposite juvenile non-operated tibias (p = 0.66) or heterochronograft tibias (p = 0.61). However, significant differences were observed between heterochrongraft tibial lengths when and opposite adult non operated tibial lengths (p < 0.001). CONCLUSIONS: Age dependent alterations affect bone quality, resulting in post transplantation osteoporosis in heterochronografts, but not isochronografts. However, the growth plates of transplanted limbs retain their properties of longitudinal growth and continue to grow at the same rate.

Chemical genetics identifies Rab geranylgeranyl transferase as an apoptotic target of farnesyl transferase inhibitors.

A chemical genetics approach identified a cellular target of several proapoptotic farnesyl transferase inhibitors (FTIs). Treatment with these FTIs caused p53-independent apoptosis in Caenorhabditis elegans, which was mimicked by knockdown of endosomal trafficking proteins, including Rab5, Rab7, the HOPS complex, and notably the enzyme Rab geranylgeranyl transferase (RabGGT). These FTIs were found to inhibit mammalian RabGGT with potencies that correlated with their proapoptotic activity. Knockdown of RabGGT induced apoptosis in mammalian cancer cell lines, and both RabGGT subunits were overexpressed in several tumor tissues. These findings validate RabGGT, and by extension endosomal function, as a therapeutically relevant target for modulation of apoptosis, and enhance our understanding of the mechanism of action of FTIs.

Pseudomyxoma peritonei: extraperitoneal spread to the pleural cavity and lung.

Abdominal and pelvic recurrence of pseudomyxoma peritonei after the surgery is occasionally seen but extraperitoneal spread and hematogeneous metastases are rare. This case of pseudomyxoma peritonei provides interesting radiologic findings of extraperitoneal spread, which occurred after an extremely long interval from initial diagnosis.

[A study for clinical correlation of neuropsychological test and brain magnetic resonance spectroscopy in patients with minimal hepatic encephalopathy].

BACKGROUND/AIMS: The aim of the study was to correlate neuropsychological test results with regional cerebral biochemistry determined by magnetic resonance spectroscopy (MRS) in patients with minimal hepatic encephalopathy (MHE). METHODS: The patients with liver disease were divided into 4 groups; group 1 chronic hepatitis; group 2, liver cirrhosis (LC) without a history of HE; group 3, LC with a history of HE of no manifestation, and group 4, LC with overt HE. All patients were examined using neuropsychological tests and brain MRS. RESULTS: Trail making, Digit span, Digit symbol, and Peg board test in groups 2 and 3 were significantly different compared with control. These neuropsychological tests were regarded more available test for diagnosis of MHE. In the LC patients, compared with control, MRS results showed a typical pattern with decrease of myoinositol/Cr (0.24+/-0.24 vs. 0.68+/-0.10, p<0.05) and increased glutamine-glutamate/Cr (2.97+/-0.80 vs. 1.94+/-0.47, p<0.05). The difference of myoinositol/Cr and glutamine-glutamate/Cr between patients with MHE and control was statistically significant (0.16+/-0.15 vs. 0.68+/-0.10, 3.11+/-0.72 vs. 1.94+/-0.47, p<0.05). CONCLUSIONS: Neuropsychological tests and MRS maybe useful for diagnosing MHE.