Alkali-Rich Antiperovskite M3FCh (M = Li, Na; Ch = S, Se, Te): The Role of Anions in Phase Stability and Ionic Transport.

To improve ionic conductivity, solid-state electrolytes with polarizable anions that weakly interact with mobile ions have received much attention, a recent example being lithium/sodium-rich antiperovskite M3HCh (M = Li, Na; Ch = S, Se, Te). Herein, in order to clarify the role of anions in antiperovskites, the M3FCh family, in which the polarizable H- anion at the octahedral center is replaced by the ionic F- anion, is investigated theoretically and experimentally. We unexpectedly found that the stronger attractive interaction between F- and M+ ions does not slow down the M+ ion diffusion, with the calculated energy barrier being as low as that of M3HCh. This fact suggests that the low-frequency rotational phonon modes of the octahedron of cubic M3FCh (and M3HCh) are intrinsic to facilitate the fast ionic diffusion. A systematic analysis further reveals a correlation between the tolerance factor t and the ionic transport: as t decreases within the cubic phase, the rotational mode becomes softer, resulting in the reduction of the migration energy. The cubic iodine-doped Li3FSe has a room-temperature ionic conductivity of 5 × 10-5 S/cm with a bulk activation energy of 0.18 eV.

Influence of the false lumen status on clinical outcomes in patients with acute type B aortic dissection.

OBJECTIVE: Clinical outcomes in acute type B aortic dissection patients with partial thrombosis of the false lumen have not been clearly elucidated. The purpose of this study was to investigate long-term mortality and incidence of surgical treatment by focusing on the status of the false lumen including partial thrombosis. METHODS: One hundred three patients (69 males, mean age 67 ± 13 years) with acute type B aortic dissection were enrolled. Patients were divided into three groups according to the status of the false lumen on enhanced computed tomography image (complete thrombosis, n = 55; partial thrombosis, n = 25; patent, n = 23). RESULTS: Requirement of surgical (open or endovascular) treatment during initial hospitalization was significantly less frequent in patients with complete thrombosis (0% in complete thrombosis, 16% in partial thrombosis, and 26% in patent). The long-term mortality (mean follow-up term, 1143 ± 933 days) did not differ among the three groups. Long-term surgical treatment-free rate was significantly lower in patients with patent false lumen. Cox regression analysis revealed that age (P < .01) and male sex (P = .013) were significant predictive factors of long-term mortality. CONCLUSIONS: In acute type B aortic dissection, the incidence of surgical treatment was higher in patients with patent false lumen during long-term follow-up, whereas status of the false lumen did not influence long-term mortality.

Decision-making deficit of a patient with axonal damage after traumatic brain injury.

Patients with traumatic brain injury (TBI) were reported to have difficulty making advantageous decisions, but the underlying deficits of the network of brain areas involved in this process were not directly examined. We report a patient with TBI who demonstrated problematic behavior in situations of risk and complexity after cerebral injury from a traffic accident. The Iowa gambling task (IGT) was used to reveal his deficits in the decision-making process. To examine underlying deficits of the network of brain areas, we examined T1-weighted structural MRI, diffusion tensor imaging (DTI) and Tc-ECD SPECT in this patient. The patient showed abnormality in IGT. DTI-MRI results showed a significant decrease in fractional anisotropy (FA) in the fasciculus between the brain stem and cortical regions via the thalamus. He showed significant decrease in gray matter volumes in the bilateral insular cortex, hypothalamus, and posterior cingulate cortex, possibly reflecting Wallerian degeneration secondary to the fasciculus abnormalities. SPECT showed significant blood flow decrease in the broad cortical areas including the ventromedial prefrontal cortex (VM). Our study showed that the patient had dysfunctional decision-making process. Microstructural abnormality in the fasciculus, likely from the traffic accident, caused reduced afferent feedback to the brain, resulting in less efficient decision-making. Our findings support the somatic-marker hypothesis (SMH), where somatic feedback to the brain influences the decision-making process.

Accelerated decline in renal function after acute myocardial infarction in patients with high low-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol ratio.

High low-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol (L/H) ratio is associated with progressions of coronary arteriosclerosis and chronic kidney disease. On the other hand, renal function markedly declined after acute myocardial infarction (AMI). The aims of the present study were (1) to identify what type of patients with AMI would have high L/H ratio at follow-up and (2) to evaluate whether decline in renal function after AMI had accelerated or not in patients with high L/H ratio. The 190 eligible AMI patients who underwent primary percutaneous coronary intervention (PCI) and received atorvastatin (10 mg) were divided into one of two groups according to the L/H ratio at 6-month follow-up: L/H >2 group (n = 81) or L/H ≤2 group (n = 109). The characteristics on admission in the two groups were examined. Furthermore, changes in serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) during 1- and 6-month follow-up were compared between the two groups. L/H >2 group were significantly younger and had greater body mass index (BMI) and worse lipid profile on admission compared with L/H ≤2 group. Percentage increase in sCr and percentage decrease in eGFR during 1-month follow-up in L/H >2 group tended to be greater than in L/H ≤2 group, and those during 6-month follow-up were significantly greater (16.5 ± 2.77 vs. 9.79 ± 2.23 %, p = 0.03 and 11.8 ± 1.93 vs. 2.75 ± 3.85 %, p = 0.04, respectively). In AMI patients undergoing primary PCI, those who were young and had large BMI and poor lipid profile on admission were likely to have a high L/H ratio at follow-up despite statin therapy. In addition, the decline in renal function after AMI had significantly accelerated in patients with high L/H ratio.

Potassium-rich antiperovskites K3HTe and K3FTe and their structural relation to lithium and sodium counterparts.

Unlike perovskite oxides, antiperovskites M3HCh and M3FCh (M = Li, Na; Ch = S, Se, Te) mostly retain their ideal cubic structure over a wide range of compositions owing to anionic size flexibility and low-energy phonon modes that promote their ionic conductivity. In this study, we show the synthesis of potassium-based antiperovskites K3HTe and K3FTe and discuss the structural features in comparison with lithium and sodium analogues. It is shown experimentally and theoretically that both compounds maintain a cubic symmetry and can be prepared at ambient pressure, in contrast to most of the reported M3HCh and M3FCh which require high pressure synthesis. A systematic comparison of a series of cubic M3HTe and M3FTe (M = Li, Na, K) revealed that telluride anions contract in the order of K, Na, Li, with a pronounced contraction in the Li system. This result can be understood in terms of the difference in charge density of alkali metal ions as well as the size flexibility of Ch anions, contributing to the stability of the cubic symmetry.

Brain structural changes and neuropsychological impairments in male polydipsic schizophrenia.

BACKGROUND: Polydipsia frequently occurs in schizophrenia patients. The excessive water loading in polydipsia occasionally induces a hyponatremic state and leads to water intoxication. Whether polydipsia in schizophrenic patients correlates with neuropsychological impairments or structural brain changes is not clear and remains controversial. METHODS: Eight polydipsic schizophrenia patients, eight nonpolydipsic schizophrenia patients, and eight healthy controls were recruited. All subjects underwent magnetic resonance imaging (MRI) and neuropsychological testing. Structural abnormalities were analyzed using a voxel-based morphometry (VBM) approach, and patients' neuropsychological function was assessed using the Brief Assessment of Cognition in Schizophrenia, Japanese version (BACS-J). RESULTS: No significant differences were found between the two patient groups with respect to the clinical characteristics. Compared with healthy controls, polydipsic patients showed widespread brain volume reduction and neuropsychological impairment. Furthermore, the left insula was significantly reduced in polydipsic patients compared with nonpolydipsic patients. These nonpolydipsic patients performed intermediate to the other two groups in the neuropsychological function test. CONCLUSIONS: It is possible that polydipsia or the secondary hyponatremia might induce left insula volume reduction. Furthermore, this structural brain change may indirectly induce more severe neuropsychological impairments in polydipsic patients. Thus, we suggest that insula abnormalities might contribute to the pathophysiology of polydipsic patients.

Development of off-axis spiral phase mirrors for generating optical vortices in a range of millimeter waves.

In this paper, we report the development of off-axis spiral phase mirrors that can be used to generate optical vortices from a range of millimeter waves. An obliquely incident Gaussian beam is reflected from a spiral phase mirror and is converted into an optical vortex beam with a desired topological charge. The mirrors were fabricated by mechanical machining. The designed vortex properties of reflected waves were investigated experimentally by using a low-power test, where the designed topological charge was verified based on the interference pattern between a vortex beam and a Gaussian-like beam. The designed topological charge was also estimated by using a phase retrieval method specialized for a vortex beam. These off-axis spiral phase mirrors can be used for propagation experiments of radio frequency waves with helical wavefronts in magnetized plasma.

Quantitative analysis of cisplatin sensitivity of human esophageal squamous cancer cell lines using in-air micro-PIXE.

Cisplatin is a key chemotherapeutic agent for the treatment of esophageal cancer. We examined the intracellular localization of cisplatin in esophageal cancer cell lines and determined their sensitivity to cisplatin using in-air micro-PIXE (particle induced X-ray emission). Two human esophageal squamous cell carcinoma (ESCC) cell lines, TE-2 and TE-13, were examined for their response to cisplatin using MTT assay, flow cytometry, and DNA fragmentation assays. Real-time reverse transcription-polymerase chain reaction was also used to evaluate the mRNA expression of multidrug resistance protein 2 (MRP2) in both cell lines. Platinum localizations of intracellular and intranuclear were measured using in-air micro-PIXE. TE-2 cells were more sensitive to cisplatin than TE-13 cells (IC(50): 37.5 mum and 56.3 mum, respectively). Flow cytometry analysis confirmed that more TE-2 than TE-13 cells were in the sub-G1 phase. DNA fragmentation assay was analyzed to confirm the MTT assay and flow cytometry results. The expression of MRP2 mRNA in TE-13 cells was stronger than in TE-2 cells. In-air micro-PIXE showed that TE-2 cells had higher intracellular cisplatin concentrations than TE-13 cells and the ratio of intranuclear to intracellular cisplatin in individual cells was not significantly different. We observed the intracellular and intranuclear localization of cisplatin using in-air micro-PIXE. The results of this study suggest that in-air micro-PIXE could be a useful quantitative method for evaluating the cisplatin sensitivity of individual cells. Finally, we speculate that MRP2 in the cell membrane may play an important role in regulating the cisplatin sensitivity of ESCC cells.

Peptides derived from a soluble molecule of the human leukocyte antigen (HLA) class I cause apoptosis in gastric cancer cell lines.

We have reported that the levels of the soluble molecule of the human leukocyte antigen class I (sHLA-I) in patients with advanced gastric cancer were significantly lower than those in patients with cancer in the early stages. However, the effect of sHLA-I on gastric cancer cells has not been elucidated. Using human gastric cancer cell lines, MKN28, MKN45, and MKN74, we evaluated the effects of sHLA-I on cell growth, DNA synthesis, and apoptosis induction. Three types of synthesized peptides derived from HLA-I were also examined for their capacity to induce apoptosis. sHLA-I and a synthesized peptide, nos. 220-232 of the alpha3 domain of HLA-B7, caused cell growth inhibition by inducing apoptosis in human gastric cancer cells. This peptide also inhibited the in vivo growth of cancer dissemination caused by an intraperitoneal injection of MKN45 into severe combined immunodeficient mice. In conclusion, sHLA-I and the peptides derived from HLA-I cause apoptosis in human gastric cancer cell lines.

Laparoscopic cholecystectomy using a novel two-port technique for surgical residency training.

For the cosmetic benefits of patients, many institutions attempted to perform laparoscopic cholecystectomy (LC) with a minimum port. It has not yet been discussed whether the number of ports used in LC affect an outcome in a residency training program. We enrolled 101 patients consecutively. Eight freshmen (PGY1) performed 32 operations (13 cases with two-port, 23 cases with four-port). Clinical data were compared with the data by the senior staff. In the freshman group, the duration of surgery was longer in the two-port group than in the four-port group (P = 0.0297); however, there were no complications. In the two-port group, the freshman group took longer than the senior group (P = 0.0266). As for the volume of intraoperative bleeding, there was no statistical significance. Our two-port technique seems to be a feasible, effective, and safe technique for performing LC in the residency training program on selected patients.

Cholesterol reduction and atherosclerosis inhibition by bezafibrate in low-density lipoprotein receptor knockout mice.

Fibrates, peroxisome proliferator-activated receptor a agonists, are widely used as lipid-lowering agents with anti-atherogenic activity. However, conflicting results have been reported with regard to their pharmacological effects on plasma lipoprotein profiles as well as on atherosclerosis in animal models. Furthermore, the anti-atherogenic effects of bezafibrate, one of the most commonly used fibrates, in animal models have not been reported. In the present study, we investigated the effects of bezafibrate on lipoprotein profiles as well as on atherosclerosis in low-density lipoprotein receptor knockout (LDLR-/-) mice fed an atherogenic diet for 8 weeks. Bezafibrate decreased plasma levels of both cholesterol and triglycerides (TG), while increasing plasma levels of high-density lipoprotein-cholesterol (HDL-C). Since hepatic TG production was significantly reduced in the bezafibrate-treated mice lacking LDLR, the plasma lipid-lowering effects of bezafibrate might be primarily mediated by the suppression of hepatic production of apolipoprotein-B-containing lipoproteins. In parallel with the reduced ratio of non-HDL-C to HDL-C, bezafibrate suppressed fatty streak lesions in the aortic sinus by 51%. To determine whether or not bezafibrate directly alters the expression of genes relevant to atherosclerosis, we measured mRNA expression levels of three genes in the aorta by real-time PCR: ATP-binding cassette transporter A1, lipoprotein lipase, and monocyte chemoattractant protein-1. The results showed that there were no differences in the expression of these genes between mice treated with bezafibrate and those not. In conclusion, bezafibrate inhibits atherosclerosis in LDLR-/- mice primarily by decreasing the ratio of non-HDL-C to HDL-C.

Laparoscopic partial liver resection for hepatocellular carcinoma in liver cirrhosis.

BACKGROUND/AIMS: Liver resection by open surgery remains the treatment of choice for hepatocellular carcinoma (HCC). However, open surgery with a large skin incision carries the possibility of liver failure in patients with advanced liver cirrhosis, because large skin incisions lead to interruption of large collateral veins. Currently, laparoscopic liver resection is preferred to avoid postoperative liver failure in these circumstances. METHODOLOGY: We describe laparoscopic treatment of three patients with a single sub glissonian HCC, using small skin incisions. The tumor lesions were located in segment 3, segment 6 and segment 8, according to Couinaud's liver anatomy on each patient. In the patient with the S8 lesion, we approached the region from the pleural cavity using a THORACO-PORT. The diaphragm was incised with a Harmonic scalpel and the tumor was removed from the pleural cavity through a 5-cm long skin incision. In the patient with S3 and that with S6 lesion, we performed mobilization of the lateral segment or the right lobe by laparoscopy. We then used a mini-retractor and Nelaton tube to bring the tumor to the subcostal region and easily performed a partial resection, which was all that could be done under the circumstances. RESULTS: All the patients were able to start oral intake on the three postoperative days, and didn't require analgesic agent. The mean post operative stay was 8.7 days. CONCLUSION: in cases of hepatocellular carcinoma that require partial liver resection, a laparoscopic procedure is a reasonable approach to surgery, because of its lower invasiveness compared with conventional liver resection.

The effect of hyperbaric oxygen treatment on postoperative morbidity of left lobe donor in living donor adult liver transplantation.

BACKGROUND/AIMS: In living donor liver transplantation (LDLT), donor safety has top priority, and donor morbidity should be minimized to zero. However, several corporal problems still remain. The effect of hyperbaric oxygenation treatment (HBO) was evaluated for donor morbidity in LDLT. METHODOLOGY: A total of 14 consecutive donors were studied. The donors into were divided into 2 groups as follows: HBO group (n=7), which started HBO 3 days after operation, and a control group (n=7). Patient's factors, graft volume, liver regeneration rate, liver function tests and postoperative complications ware compared between the 2 groups. RESULTS: There was no significant difference between the groups in whole liver, graft and remnant liver volume. The incidence of wound numbness on POD 28 was 86% (6/7) in the control group and 29% (2/7) in the HBO group (p<0.05). Postoperative hospital stay was 14.4 and 14.6 days in the control and HBO group, respectively (p=NS). On POD 14, AST value in the HBO group was significantly lower than in the control group (p<0.05). PT% value in the HBO group was significantly higher than in the control group on POD 14 (p<0.05). Total bilirubin level in the HBO group was significantly lower than in the control group on POD 14 and 28 (p<0.05), and total bile acid value in the HBO group was significantly lower than the control group (p<0.05) on POD 14. Albumin level in the HBO group was significantly higher than the control group on POD 7, 10 and 28 (p<0.05). Four weeks after the operation, the regeneration rate was significantly higher in the HBO group than in the control group (p<0.05). CONCLUSIONS: Liver regeneration was promoted by HBO preserving a function in LDLT using left lobe graft. Hyperbaric oxygen therapy seems to be very useful to LDLT.

Development of a noninvasive method to measure intravascular and intracardiac pressure differences using magnetic resonance imaging.

PURPOSE: We developed a noninvasive method using magnetic resonance (MR) imaging to measure differences in intravascular and intracardiac pressure, and we investigated the feasibility of the method's use in a pulsatile flow phantom and human studies. METHODS: We measured 3 velocity components using phase contrast MR imaging on a 1.5T MR scanner, used velocity data in Navier-Stokes equations to obtain pressure gradients, and directly integrated the in-plane pressure gradients to calculate pressure differences. To validate our method, we compared the pressure differences obtained by our method with the theoretical values obtained from an axisymmetric model of arterial stenosis. We also estimated the pressure differences in glass-tube phantoms simulating various vascular pathologies and in the left ventricle and aortic arch of a normal volunteer as clinical application. RESULTS: The pressure differences obtained by our method agreed well with theoretical values obtained using the straight-tube phantom with stenosis of 45%, but we observed some differences when stenosis was 65%. We clearly observed variations in pressure differences at specific locations at various phases of a cardiac cycle in both phantom and human studies. CONCLUSION: This method appears useful for measuring intravascular and intracardiac pressure differences.

The soluble form of human leukocyte antigen class I antigen causes apoptosis on hepatocellular carcinoma cell lines.

A soluble form of human leukocyte antigen class I antigen (sHLA-I) has been reported to cause apoptosis on cytotoxic T cells and inhibit killer activity of natural killer cells via killer-cell inhibitory receptors. However, its effect on cancer cells has not yet been elucidated. We examined the direct effect of sHLA-I on human liver cancer cell lines, HepG2, HLE and HLF. The effects of sHLA-I on cell growth, DNA synthesis, and apoptosis induction were evaluated. To elucidate the mechanisms, cDNA expression arrays were also examined. sHLA-I caused cell growth inhibition, resulting in apoptosis on human hepatocellular carcinoma, dose-dependently. In this process, caspase-3 was activated. sHLA-I also inhibited in vivo growth of hepatocellular carcinoma in severe combined immunodeficient mice. sHLA-I caused apoptosis on human hepatocellular carcinoma.

Laparoscopy-assisted distal pancreatectomy with mobilization of the distal pancreas and the spleen outside the abdominal cavity.

Laparoscopic ligation of the peripancreatic vessels or duct requires a particularly skillful technique. If the pancreatic tail and the spleen can be mobilized outside of the abdominal cavity, surgeons can perform these procedures as easily as ordinary open surgery. We developed a novel approach to laparoscopy-assisted distal pancreatectomy without hand-assist. In brief, the pancreatic tail and the spleen were mobilized laparoscopically from the retroperitoneum until the celiac axis was exposed, then the pancreatic tail and the spleen were laparoscopically mobilized outside the peritoneal cavity from a small incision at the upper abdomen. After mobilization, the distal pancreatectomy was performed as usual open method. This approach offers better results in coping with organs, which seem to be difficult to resect through laparoscopic surgery alone.

Lack of circadian change of concentration of C-type natriuretic peptide in rabbit aqueous humor.

PURPOSE: To determine whether there is a circadian change of the concentration of C-type natriuretic peptide (CNP) in rabbit aqueous humor. METHODS: Forty-one male white New Zealand rabbits were submitted to a 12 h light and 12 dark lighting schedule; lights on was at 0 h, lights off at 12 h. C-type natriuretic peptide was assayed at 3 light (2 h, 6 h and 10 h) and 3 dark (14,18 and 22 h) times. All groups consisted of four animals but two had more animals to increase the power of tests (6 h, n = 12; 22 h, n = 13). Dependence between the two eyes was tested by Pearson's correlation. The mean of two eyes was considered for analysis. Differences in concentration in pg/200 ml were evaluated by one-way ANOVA, t test and COSINOR analysis. RESULTS: There were no significant differences between the 6 analyzed groups (one-way ANOVA p = 0.157). Pooled into two groups (light and dark), the C-type natriuretic peptide concentration of the light group was lower, 2.626 +/- 0.92 pg/200 ml compared with the dark group 3.02 +/- 1.16 pg/200 ml but did not reach a significant difference (t test; p = 0.23). COSINOR analysis was not statistically significant (R% = 7.72 p = 0.209). CONCLUSION: These data demonstrate that the concentration of CNP in aqueous humor did not show a statistically significant circadian change in rabbits entrained to a 12 h light: 12 h dark lighting schedule.

A longitudinal, event-related potential pilot study of adult obsessive-compulsive disorder with 1-year follow-up.

AIM: Earlier brain imaging research studies have suggested that brain abnormalities in obsessive-compulsive disorder (OCD) normalize as clinical symptoms improve. However, although many studies have investigated event-related potentials (ERPs) in patients with OCD compared with healthy control subjects, it is currently unknown whether ERP changes reflect pharmacological and psychotherapeutic effects. As such, the current study examined the neurocognitive components of OCD to elucidate the pathophysiological abnormalities involved in the disorder, including the frontal-subcortical circuits. METHODS: The Yale-Brown Obsessive-Compulsive Scale was used to evaluate 14 adult patients with OCD. The present study also included ten age-, sex-, and IQ-matched controls. The P300 and mismatch negativity (MMN) components during an auditory oddball task at baseline for both groups and after 1 year of treatment for patients with OCD were measured. RESULTS: Compared with controls, P300 amplitude was attenuated in the OCD group at Cz and C4 at baseline. Pharmacotherapy and psychotherapy treatment for 1 year reduced OCD symptomology. P300 amplitude after 1 year of treatment was significantly increased, indicating normalization compared with baseline at Fz, Cz, C3, and C4. We found no differences in P300 latency, MMN amplitude, or MMN latency between baseline and after one year of treatment. CONCLUSION: ERPs may be a useful tool for evaluating pharmacological and cognitive behavioral therapy in adult patients with OCD.

MIB-1 labeling index, Ki-67, is an indicator of invasive intraductal papillary mucinous neoplasm.

Despite strict criteria for the observation of intraductal papillary mucinous neoplasm (IPMN), it remains difficult to distinguish invasive IPMN from non-invasive IPMN. The aim of the present study was to identify an indicator of invasive IPMN. The present study retrospectively evaluated 53 patients (28 with non-invasive and 25 with invasive IPMN) who underwent resection of IPMN, and examined the usefulness of the MIB-1 labeling index as an indicator of invasive IPMN. The MIB-1 labeling indexes in patients with invasive IPMN were significantly higher compared with those with non-invasive IPMN (P<0.001). A receiver operating characteristic curve revealed that the area under the curve was 0.822. These results suggested that a cut-off level for the MIB-1 labeling index should be set to 15.5% to distinguish invasive from non-invasive IPMN. A multivariate analysis using a logistic regression model revealed the MIB-1 labeling index (hazard ratio, 18.692; 95% confidential interval, 4.171-83.760; P<0.001) and the existence of mural nodules (hazard ratio, 6.187, 95% confidential interval, 1.039-36.861; P=0.045) were predictive factors for invasive IPMN. However, no statistically significant differences were observed between patients with a lower MIB-1 labeling index and patients with a higher MIB-1 labeling index (P=0.798). The MIB-1 labeling index must be considered as a candidate for the classification of IPMN.

Clinical features and course of patients with glaucoma with the E50K mutation in the optineurin gene.

PURPOSE: To investigate the clinical features of subjects with glaucoma with the E50K mutation in the optineurin (OPTN) gene and to compare the onset, severity, and clinical course of these patients with a control group of subjects with glaucoma without this mutation. METHODS: The phenotype of well-characterized subjects from Moorfields Eye Hospital, London, who had been identified as carrying the OPTN E50K mutation was examined. A wide range of structural, psychophysical, and demographic factors were then compared with those in a control group of subjects with glaucoma without this mutation. RESULTS: Eleven subjects with glaucoma with the E50K mutation (nine in two families and two sporadic cases) were studied. All 11 subjects had normal tension glaucoma (NTG), with presenting and highest IOP of 15.3 +/- 3.0 and 16.5 +/- 2.5 mm Hg (+/-SD) on diurnal testing. Compared with 87 NTG control subjects who did not have this mutation, subjects with E50K presented at a younger age (40.8 +/- 15 years, P = 0.0001) and had more advanced optic disc cupping (mean cup-disc ratio +/- SD 0.86 +/- 0.1, P = 0.001) and smaller neuroretinal rim area (+/-SD; 0.5 +/- 0.28 mm2, P = 0.001) at diagnosis. The rate of filtration surgery performed for progressive visual field loss in those with and without the E50K mutation was 72.7% and 25.3%, respectively (P = 0.003), and all subjects with E50K were found to have progressing visual fields. In addition, seven E50K mutation-carrying individuals in two families (age range, 23-58 years) presented with normal optic discs and visual fields and, as yet, no signs of glaucoma. CONCLUSIONS: In this study, subjects with glaucoma who had the OPTN E50K mutation were found to have NTG that appeared to be more severe than that in a control group of subjects with NTG without this mutation. The findings emphasize the importance of early detection and treatment of glaucoma in such individuals, to minimize visual loss.