Circulating miRNA-4701-3p as a predictive biomarker of cardiovascular disease which induces angiogenesis by inhibition of TOB2.

Angiogenesis is mainly regulated by the delivery of VEGF-dependent signaling to cells. However, the angiogenesis mechanism regulated by VEGF-induced miRNA is still not understood. After VEGF treatment in HUVECs, we screened the changed miRNAs through small-RNA sequencing and found VEGF-induced miR-4701-3p. Furthermore, the GFP reporter gene was used to reveal that TOB2 expression was regulated by miR-4701-3p, and it was found that TOB2 and miR-4701-3p modulation could cause angiogenesis in an in-vitro angiogenic assay. Through the luciferase assay, it was confirmed that the activation of the angiogenic transcription factor MEF2 was regulated by the suppression and overexpression of TOB2 and miR-4701-3p. As a result, MEF2 downstream gene mRNAs that induce angiogenic function were regulated. We used the NCBI GEO datasets to reveal that the expression of TOB2 and MEF2 was significantly changed in cardiovascular disease. Finally, it was confirmed that the expression of circulating miR-4701-3p in the blood of myocardial infarction patients was remarkably increased. In patients with myocardial infarction, circulating miR-4701-3p was increased regardless of age, BMI, and sex, and showed high AUC levels in specificity and sensitivity analysis (AUROC) (AUC = 0.8451, 95 % CI 0.78-0.90). Our data showed TOB2-mediated modulation of MEF2 and its angiogenesis by VEGF-induced miR-4701-3p in vascular endothelial cells. In addition, through bioinformatics analysis using GEO data, changes in TOB2 and MEF2 were revealed in cardiovascular disease. We suggest that circulating miR-4701-3p has high potential as a biomarker for myocardial infarction.

Factors Affecting Delirium in ICU Patients.

This study examined delirium severity using a delirium screening tool and analyzed the predictors, including pain, acuity, level of consciousness, fall risk, and pain score, to increase understanding of delirium and present foundational data for developing nursing interventions for delirium prevention. This was a retrospective study of 165 patients admitted to three intensive care units (ICUs). the Nursing Delirium Screening Scale (Nu-DESC) was used as a research tool to screen for delirium and measure the degree of delirium. The incidence of delirium in patients was 53.3%, and the average delirium score in the delirium group was 2.40 ± 0.56. Nu-DESC scores were significantly correlated with ICU days, ventilator days, restraint applications, the number of catheters inserted, sedative medication use, the Simplified Acute Physiology Score (SAPS III), the Morse Fall Scale (MFS), the Glasgow Coma Scale (GCS) scores, pain scores, and blood urea nitrogen (BUN). Stepwise multiple linear regression showed that the number of restraint applications, GCS score, ICU days, and BUN levels were factors influencing delirium. Based on the findings, ICU nurses should use delirium screening tools to ensure accurate delirium screening and work to reduce the incidence and degree of delirium by observing factors affecting delirium in patients.

Effects of genomic estimated breeding value and dietary energy to protein ratio on growth performance, carcass trait, and lipogenic gene expression in Hanwoo steer.

"Genome-based precision feeding" is a concept that involves the application of customised diets to different genetic groups of cattle. We investigated the effects of the genomic estimated breeding value (gEBV) and dietary energy to protein ratio (DEP) on growth performance, carcass traits, and lipogenic gene expression in Hanwoo (Korean cattle) steers. Forty-four Hanwoo steers (BW = 636 kg, age = 26.9 months) were genotyped using the Illumina Bovine 50 K BeadChip. The gEBV was calculated using genomic best linear unbiased prediction. Animals were separated into high gEBV of marbling score or low-gMS groups based on the upper and lower 50% groupings of the reference population, respectively. Animals were assigned to one of four groups in a 2 × 2 factorial arrangement: high gMS/high DEP (0.084 MJ/g), high gMS/low DEP (0.079 MJ/g), low gMS/high DEP, and low gMS/low DEP. Steers were fed concentrate with a high or low DEP for 31 weeks. The BW tended to be higher (0.05 < P < 0.1) in the high-gMS groups compared to the low-gMS groups at 0, 4, 8, 12, and 20 weeks. The average daily gain (ADG) tended to be lower (P = 0.08) in the high-gMS group than in the low-gMS group. Final BW and measured carcass weight (CW) were positively correlated with the gEBV of carcass weight (gCW). The DEP did not affect ADG. Neither the gMS nor the DEP affected the MS and beef quality grade. The intramuscular fat (IMF) content in the longissimus thoracis (LT) tended to be higher (P = 0.08) in the high-gMS groups than in the low-gMS groups. The mRNA levels of lipogenic acetyl-CoA carboxylase and fatty acid binding protein 4 genes in the LT were higher (P < 0.05) in the high-gMS group than in the low-gMS group. Overall, the IMF content tended to be affected by the gMS, and the genetic potential (i.e., gMS) was associated with the functional activity of lipogenic gene expression. The gCW was associated with the measured BW and CW. The results demonstrated that the gMS and the gCW may be used as early prediction indexes for meat quality and growth potential of beef cattle.

Effect of Treatment Adherence Improvement Program in Hemodialysis Patients: A Systematic Review and Meta-Analysis.

Herein, we performed a meta-analysis evaluating the effects of treatment adherence enhancement programs on treatment adherence and secondary outcomes for hemodialysis patients. Twenty-five Korean and international articles published prior to 31 March 2022 were selected following the PRISMA and Cochrane Systematic Review guidelines. We calculated summary effect sizes, conducted homogeneity and heterogeneity testing, constructed a funnel plot, and performed Egger's regression test, Begg's test, trim-and-fill method, subgroup analyses, and univariate meta-regression. The overall effect of treatment adherence enhancement programs for hemodialysis patients was statistically significant (Hedges' g = 1.10, 95% CI: 0.77, 1.43). On performing subgroup analysis to determine the cause of effect size heterogeneity, statistically significant moderating effects were found for a range of input variables (Asian countries, study centers, sample size, study design, intervention types, number of sessions, quality assessment scores, funding, and evidence-based interventions). On univariate meta-regression, larger synthesized effect sizes were found for a range of study characteristics (Asian populations, single-center studies, studies with <70 participants, quasi-experimental studies, educational interventions, studies with >12 sessions, studies with quality assessment scores above the mean, unfunded studies, and non-theory-based interventions). Our results provide evidence-based information for enhancing program efficacy when designing treatment adherence enhancement programs for hemodialysis patients.

Over 500 Liver Transplants Including More Than 400 Living-Donor Liver Transplants in 2019 at Asan Medical Center.

BACKGROUND: More than 400 liver transplants were performed at Asan Medical Center (AMC) in 2011, and over 500 liver transplants including 420 living-donor liver transplants (LDLTs) were performed in 2019. Herein, we report the methodology of these procedures. METHODS: Since the first adult LDLTs at AMC using the left and right lobes were successfully performed, various innovative techniques and approaches have been developed: modified right lobe, dual graft, donor exchange for ABO incompatibility, expansion of indications and no-touch techniques for hepatocellular carcinoma, intraoperative cine-portogram and additional intervention for large collaterals, management of portal vein thrombosis (PVT) and stenosis, salvage LDLT after major hepatectomy, and timely LDLT for patients with acute-on-chronic liver failure. RESULTS: Four hundred twenty LDLTs in 403 adult and 17 pediatric patients and 85 deceased-donor liver transplants in 74 adult and 11 pediatric patients were performed. The number of deceased-donor liver transplants remained constant since 2011, but the number of LDLTs increased steadily. One hundred thirty patients (25.7%) required urgent liver transplantations and 24 patients with acute-on-chronic liver failure underwent LDLT. PVT including grade 1,2,3, and 4 was reported in 91 patients (18.0%), and Yerdel's grade 2, 3, and 4 PVT was reported in 47 patients (51.6%); all patients with PVT were successfully treated. Adult LDLTs for hepatocellular carcinoma and ABO incompatibility accounted for 52.6% and 24.3% of the cases, respectively. In-hospital mortality in 2019 was 2.97%. CONCLUSION: Continual efforts to overcome challenging problems in LDLT with various innovations and dedication of the team members during the perioperative period to improve patient outcomes were crucial in increasing the number of liver transplantations at Asan Medical Center.

Lupus Low Disease Activity State Achievement Is Important for Reducing Adverse Outcomes in Pregnant Patients With Systemic Lupus Erythematosus.

OBJECTIVE: This study aimed to examine the frequency and risk factors of complications during pregnancy in women with systemic lupus erythematosus (SLE). METHODS: The medical records of patients with SLE and age-matched controls at Ajou University Hospital were collected. Clinical features and pregnancy complications in women with SLE were compared to those of the controls. Multivariate logistic regression analysis was performed to determine the predictors of adverse maternal and fetal outcomes. RESULTS: We analyzed 163 pregnancies in patients with SLE and 596 pregnancies in the general population; no significant differences regarding demographic characteristics were noted. Patients with SLE experienced a higher rate of stillbirth (OR 13.2), preeclampsia (OR 4.3), preterm delivery (OR 2.8), intrauterine growth retardation (OR 2.5), admission to neonatal intensive care unit (OR 2.2), and emergency cesarean section (OR 1.9) than the control group. Multivariate regression analysis revealed that thrombocytopenia, low complement, high proteinuria, high SLE Disease Activity Index (SLEDAI), low Lupus Low Disease Activity State (LLDAS) achievement rate, and high corticosteroid (CS) dose were associated with adverse pregnancy outcomes. In the receiver-operating characteristic curve analysis, the optimal cutoff value for the cumulative and mean CS doses were 3500 mg and 6 mg, respectively. CONCLUSION: Pregnant women with SLE have a higher risk of adverse pregnancy outcomes. Pregnancies are recommended to be delayed until achieving LLDAS and should be closely monitored with the lowest possible dose of CS.

Life-Threatening Portal Flow Steal Reappearing Under Increased Intrahepatic Vascular Resistance After Living Donor Liver Transplantation.

Maintenance of adequate portal inflow is crucial for graft regeneration in adult living donor liver transplantation (ALDLT) to allow the recipients to meet their early metabolic demands. A persistent large spontaneous portosystemic shunt can divert portal flow away from the liver graft, leading to impaired or delayed graft regeneration and subsequent graft failure. The importance of obliterating huge portosystemic shunt during liver transplantation is obvious for successful ALDLT. However, in partial liver graft with a relatively small graft-to-recipient weight ratio (GRWR) (compared with deceased donor whole graft liver transplantation), even the persisting small portosystemic shunt may result in repeated portal flow steal when a liver graft faces increased intrahepatic vascular resistance caused by rejection or graft congestion with hepatic venous outflow stenosis. We present 2 complicated cases of reappearing portal flow steal that were derived from the remaining small portosystemic shunt under the increased vascular resistance of the liver graft, even after interruption of a large portosystemic shunt during ALDLT. Because ALDLT is always a partial liver graft, even when GRWR is over 1%, it is much more vulnerable to hemodynamic changes in portal flow by rejection or graft congestion by hepatic venous outflow obstruction. Therefore, a comprehensive understanding of complex portosystemic shunt and complete reinterruption of reappearing portosystemic shunt, even though small and insignificant, during ALDLT is important for graft salvage procedures before irreversible liver graft damage.

Technical refinement of prosthetic vascular graft anastomosis to recipient inferior vena cava for secure middle hepatic vein reconstruction in living donor liver transplantation.

BACKGROUNDS/AIMS: Hemashield vascular grafts has been used for middle hepatic vein (MHV) reconstruction during living donor liver transplantation (LDLT). We occasionally encounter outflow disturbance of MHV conduit at the anastomotic stump of the middle-left hepatic vein (MLHV) trunk. To mitigate the disturbance, we carried out a series of studies regarding hemodynamics-compliant MHV reconstruction. METHODS: This study comprised of three parts: Part 1: Determining the causes of outflow disturbance; Part 2: Computational simulative analysis; and, Part 3: Clinical application of our refined technique. The types of Hemashield conduit-MLHV stump reconstruction were end-to-end anastomosis (type 1), side-to-end anastomosis (type 2), and oblique cutting of the conduit end and patch plasty (type 3). RESULTS: In Part 1 study, the reconstruction types were type 1 in 23, type 2 in 25, and type 3 in 2. Significant anastomotic stenosis was identified in 7 (30.4%) in type 1, 6 (24.0%) in type 2, and none (0%) in type 3. The size of MLHV stump was the most important factor for anastomotic stenosis. Through Part 2 study, technical knacks were developed as follows: the conduit end was cut in a dumb-bell shape and a vessel patch attached; and then sutured bidirectionally from the 9 o'clock direction. In Part 3 study, these knacks were applied to 5 patients and none of them experienced noticeable anastomotic stenosis. CONCLUSIONS: Our refined technique to perform conduit-MLHV stump anastomosis appears to reduce the risk of anastomotic outflow disturbance for relatively small MLHV stump.

Determination of Hepatitis B Immunoglobulin Infusion Interval Using Pharmacokinetic Half-life Simulation for Posttransplant Hepatitis B Prophylaxis.

BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. This study established an individualized HBV prophylaxis protocol, through optimization of hepatitis B immunoglobulin (HBIG) administration, with application of simulative half-life (SHL). METHODS: This study involved five parts: Part 1 developed the SHL estimation method with 20 patients; Parts 2 and 3 assessed the SHL variability and developed a simulation model to apply SHL in 100 patients; Part 4 validated the simulation model in 114 patients, and Part 5 was a cross-sectional study on the current status of HBIG infusion intervals in 660 patients. RESULTS: In Part 1, infusion of 10,000 IU HBIG induced add-on rise hepatitis B surface antibody (anti-HBs) titer of 5,252.5 ± 873.7 IU/L, which was 4.4% lower than actual measurement. Mean SHL of 20.0 ± 3.7 days was 2.2% longer than actual measurement. In Part 2, the medians of the intra- and inter-individual coefficient of variation in SHL were 13.5% and 18.5%, respectively. Pretransplant HBV DNA load and posttransplant antiviral therapy did not affect SHL. In Part 3, a simulation model was developed to determine the interval of HBIG infusion, by using SHL. In Part 4, all 114 patients were successfully managed with regular HBIG infusion intervals of ≥ 8 weeks, and the interval was prolonged to ≥ 12 weeks in 89.4%, with a target trough anti-HBs titer ≥ 200 IU/L. In Part 5, 47.4% of our patients received HBIG excessively, at a target trough titer of 500 IU/L. CONCLUSION: SHL estimation using only clinically available parameters seems to be reliably accurate when compared with actual measurements. We believe that SHL estimation is helpful to establish a personalized HBV prophylaxis protocol for optimizing HBIG administration.

Assessment of patient safety and the efficiency of facility utilization following simplified ultra-rapid intravenous infusion of hepatitis B immunoglobulin in a high-volume liver transplantation center.

BACKGROUNDS/AIMS: This study intended to evaluate patient safety and efficiency of facility utilization following simplified ultra-rapid intravenous infusion of hepatitis B immunoglobulin (HBIG) in recipients of hepatitis B virus-associated adult liver transplantation (LT), who visited our outpatient clinic. METHODS: Our simplified ultra-rapid infusion protocol was to directly infuse 50 ml volume of 10,000 IU HBIG for 20-25 minutes on an ambulatory basis. The incidence of adverse side-effects and the efficiency of facility utilization were assessed retrospectively. RESULTS: A total of 1,513 patients received 12,472 sessions of HBIG infusion according to simplified ultra-rapid infusion method. Of these, 1,172 patients were converted from conventional ultra-rapid infusion method, and received 8,352 sessions of HBIG infusion for 18 months (mean 7.1 times; 4.8 times per year). The remaining 341 de novo patients received 4,120 sessions of HBIG infusion for 18 months (mean 12.1 times; 8.1 times per year). None of these patients experienced any adverse side-effects following the simplified ultra-rapid infusion. The maximal capacity of HBIG infusion sessions at the injection facility of our outpatient clinic was increased from 65-70 sessions to 80 sessions, after introduction of simplified ultra-rapid infusion method. Mean trough anti-HBs titer was lower, and mean interval of HBIG infusion was longer in the combination therapy group compared with HBIG monotherapy group. CONCLUSIONS: Our high-volume study indicates that in nearly all LT recipients, rapid infusion of highly purified HBIG within 30 minutes was well-tolerated. This suggests that it would be reasonable to perform simplified ultra-rapid infusion protocol widely for patient convenience.

Factors associated with regression from prediabetes to normal glucose tolerance in a Korean general population: A community-based 10-year prospective cohort study.

AIM: A proportion of people with prediabetes convert back to normal glucose tolerance. We sought to determine the clinical variables associated with conversion from prediabetes to normal glucose tolerance, with a focus on insulin secretory capacity, insulin sensitivity and body composition. METHODS: We followed 1731 people with prediabetes at baseline from the Korean Genome and Epidemiology Study every 2 years for 10 years. Oral glucose tolerance tests (OGTT) were performed, and muscle and fat mass were estimated using bioelectrical impedance analysis. RESULTS: During 10 years of follow-up, 36% (623/1731) of people with prediabetes converted to normal glucose tolerance. Higher baseline fasting glucose, 2-h OGTT glucose and triglyceride levels were inversely associated with this conversion. Higher 60-min insulinogenic index (IGI60 ) at baseline was independently associated with this conversion [HR per sd (95% CI) 1.09 (1.02-1.17); P = 0.01]. However, other indices reflecting insulin sensitivity, including the composite insulin sensitivity index, were not associated with this conversion. In addition, a higher baseline muscle to fat ratio was independently associated with conversion to normal glucose tolerance [HR per sd (95% CI) 1.15 (1.04-1.26); P = 0.005]. People with conversion to normal glucose tolerance showed a greater increase in the 60-min insulinogenic index and disposition index and a smaller decrease in the composite insulin sensitivity index compared with people without conversion during 10 years of follow-up (all p-values < 0.001). CONCLUSION: A higher insulin secretory capacity at baseline and during follow-up and higher baseline muscle to fat ratio were independently associated with an improvement in glucose tolerance in Korean adults with prediabetes.

Improved recombinant protein production in Arabidopsis thaliana.

Production and isolation of recombinant proteins are key steps in modern Molecular Biology. Expression vectors and platforms for various hosts, including both prokaryotic and eukaryotic systems, have been used. In basic plant research, Arabidopsis thaliana is the central model for which a wealth of genetic and genomic resources is available, and enormous knowledge has been accumulated over the past years - especially since elucidation of its genome in 2000. However, until recently an Arabidopsis platform had been lacking for preparative-scale production of homologous recombinant proteins. We recently established an Arabidopsis-based super-expression system, and used it for a structural pilot study of a multi-subunit integral membrane protein complex. This review summarizes the benefits and further potential of the model plant system for protein productions. ABBREVIATIONS: Nb, Nicotiana benthamiana; OT, oligosaccharyltransferase.

Characteristics and prognosis of breast cancer after liver or kidney transplantation.

PURPOSE: Immunoediting is crucial in cancer development and progression. This study compared the characteristics and prognosis of post-transplant breast cancer (PTBC) patients receiving immunosuppressants and general breast cancer patients. METHODS: Data from the Asan Medical Center Breast Cancer (AMCBC), kidney transplantation, and liver transplantation databases recorded during 1989-2013 were retrospectively analyzed. Four controls of AMCBC cohort per one case of PTBC cohort were selected based on tumor size, lymph node metastasis, and age. RESULTS: After a median of 61 and 90.8 months after liver and kidney transplantation, respectively, 8 and 16 patients were diagnosed with breast cancer, respectively (p = 0.178). Mean age at breast cancer diagnosis was 51.9 (±8.7) and 45.2 (±4.5) years in liver and kidney transplantation patients, respectively. Age at diagnosis was significantly younger in kidney transplantation patients than in general breast cancer patients (45.2 ± 4.5 vs. 48.5 ± 10.1 years; p = 0.008). Cancer was detected via asymptomatic screening in 41.7% of the PTBC cohort but 30.6% of the control cohort (p = 0.241). In the PTBC cohort, 7 (29.2%) patients had stage 0 breast cancer compared with 1704 (9.7%) in the control cohort (p = 0.022); 22 (91.7%) patients had lymph node-negative cancer compared with 11,704 (66.8%) in the control cohort (p = 0.01). Estrogen receptor, progesterone receptor, and HER2 positivity did not differ between cohorts. Immunosuppressant use was not a poor prognostic factor for breast cancer patients. CONCLUSIONS: Age at breast cancer diagnosis was younger in patients who received kidney transplants; the subtype and prognosis of breast cancer were comparable with that in the general cohort. Immunosuppressants do not adversely affect breast cancer prognosis.

Monitoring rate and predictability of intraoperative monitoring in patients with intradural extramedullary and epidural metastatic spinal tumors.

STUDY DESIGN: Single-center retrospective study. OBJECTIVES: To evaluate the monitoring rate, sensitivity and specificity of intraoperative monitoring (IOM) during removal of intradural extramedullary (IDEM) or epidural metastatic spinal tumors. Also, to assess the efficacy of monitoring somatosensory-evoked potentials (SSEP) when motor-evoked potentials (MEP) are not measurable. SETTING: The Neuro-Oncology Clinic, National Cancer Center, Korea. METHODS: Patients (n=101) with IDEM or epidural metastatic spinal tumors at the cord level underwent surgeries monitored with SSEP and/or MEP. The monitoring rate was defined as negative when MEP or SSEP could not be measured after reversal of the neuromuscular block under general anesthesia. Positive IOM changes included more than a 50% change in the MEP or SSEP amplitude and more than a 10% delay in SSEP latency. RESULTS: MEP was measurable in 73% of patients. The MEP monitoring rate in patients with motor power grades of 3 or less was 39%, which was lower than that of SSEP (83%). The sensitivity, specificity and predictability of MEP for motor changes were 93, 90 and 91%, respectively. Conversely, the sensitivity, specificity and predictability of SSEP were 62, 97 and 89%, respectively. In patients in whom MEP was not measurable (n=24), SSEP was monitored with a predictability of 83%. CONCLUSION: In cases of extramedullary spinal tumors, MEP shows a higher sensitivity than SSEP does. However, the monitoring rate of MEP in non-ambulatory patients was lower than that of SSEP. In those cases, SSEP can be useful to monitor for postoperative neurological deficits.

Normal-appearing white matter demyelination in neuromyelitis optica spectrum disorder.

BACKGROUND AND PURPOSE: Increasing evidence suggests the presence of demyelination in the normal-appearing white matter (NAWM) of patients with neuromyelitis optica spectrum disorder (NMOSD). The objective was to determine the presence of subclinical demyelination in the NAWM of patients with NMOSD using myelin water imaging (MWI). METHODS: Whole brain and regions-of-interest (ROIs) analyses, including the centrum semiovale, corona radiata, genu and splenium of the corpus callosum, and optic radiation, were conducted in the NAWM of 28 NMOSD patients and 18 healthy controls (HCs) using two MWI modalities: conventional MWI and direct visualization of short transverse relaxation time component (ViSTa) MWI. RESULTS: Conventional myelin water fractions (MWFs) of the global NAWM and three ROIs (centrum semiovale, corona radiata, and genu of the corpus callosum) were slightly lower in NMOSD patients than in HCs, although not statistically significant. On the other hand, ViSTa MWF values of the global NAWM and all ROIs except the genu of the corpus callosum were significantly lower in NMOSD patients relative to HCs. In particular, the MWF in the optic radiation was significantly reduced in NMOSD patients relative to HCs in both MWI methods, even in patients who had no brain involvement. Additionally, patients with optic neuritis showed lower MWF than patients without optic neuritis and a negative correlation was identified between the MWF of the optic radiation and visual functional system score. CONCLUSIONS: This study identified the presence of widespread demyelination in the NAWM of NMOSD patients and highlighted the optic radiation as a site of marked demyelination.

Widespread cortical thinning in patients with neuromyelitis optica spectrum disorder.

BACKGROUND AND PURPOSE: Studies on cortical involvement and its relationship with cognitive function in patients with neuromyelitis optica spectrum disorder (NMOSD) remain scarce. The objective of this study was to compare cortical thickness on magnetic resonance imaging (MRI) between patients with NMOSD and multiple sclerosis (MS) and to investigate its relationship with clinical features and cognitive function. METHODS: This observational clinical imaging study of 91 patients with NMOSD, 52 patients with MS and 44 healthy controls was conducted from 1 December 2013 to 30 April 2015 at the institutional referral center. Three tesla MRI of the brain and neuropsychological tests were performed. Cortical thickness was measured using three-dimensional surface-based analysis. RESULTS: Both sets of patients exhibited cortical thinning throughout the entire brain cortex. Patients with MS showed a significantly greater reduction in cortical thickness over broad regions of the bilateral frontal and parieto-temporal cortices and the left precuneus compared to those with NMOSD. Memory functions in patients with MS were correlated with broad regional cortical thinning, whereas no significant associations were observed between cortical thickness and cognitive function in patients with NMOSD. CONCLUSIONS: Widespread cortical thinning was observed in patients with NMOSD and MS, but the extent of cortical thinning was greater in patients with MS. The more severe cortical atrophy may contribute to memory impairment in patients with MS but not in those with NMOSD. These results provide in vivo evidence that the severity and clinical relevance of cortical thinning differ between NMOSD and MS.

Color moiré simulations in contact-type 3-D displays.

A new method of color moiré fringe simulation in the contact-type 3-D displays is introduced. The method allows simulating color moirés appearing in the displays, which cannot be approximated by conventional cosine approximation of a line grating. The color moirés are mainly introduced by the line width of the boundary lines between the elemental optics in and plate thickness of viewing zone forming optics. This is because the lines are hiding some parts of pixels under the viewing zone forming optics, and the plate thickness induces a virtual contraction of the pixels. The simulated color moiré fringes are closely matched with those appearing at the displays.

Gemcitabine-oxaliplatin plus prednisolone is active in patients with castration-resistant prostate cancer for whom docetaxel-based chemotherapy failed.

BACKGROUND: There has been no previous study on the activity of gemcitabine in combination with oxaliplatin (GemOx) for castration-resistant prostate cancer (CRPC). METHODS: The GemOx was preclinically tested for cytotoxic activity in human prostate cancer cell lines. Clinically, patients with CRPC who failed prior docetaxel were treated with gemcitabine 1000 mg m(-2) and oxaliplatin 100 mg m(-2) intravenously every 2 weeks and prednisolone 5 mg orally twice daily. The primary end point was the prostate-specific antigen (PSA) response rate. RESULTS: The GemOx displayed synergistic effects based on Chou and Talalay analysis. In the phase II study, 33 patients were accrued. The median dose of docetaxel exposure was 518 mg m(-2). A total of 270 cycles were administered with a median of eight cycles per patient. A PSA response rate was 55% (95% CI, 38-72) and radiologic response rate was 82% (9 out of 11). With a median follow-up duration of 20.5 months, the median time to PSA progression was 5.8 months (95% CI, 4.4-7.2) and the median overall survival was 17.6 months (95% CI, 12.6-22.6). The most frequently observed grade 3 or 4 toxicities were neutropenia (13%) and thrombocytopenia (13%). CONCLUSIONS: The GemOx is active and tolerable in patients with metastatic CRPC after docetaxel failure (NCT 01487720).