TGFß4 alleviates the phenotype of Charcot-Marie-Tooth disease type 1A.

The duplication of the peripheral myelin protein 22 (PMP22) gene causes a demyelinating type of neuropathy, commonly known as Charcot-Marie-Tooth disease type 1A (CMT1A). Development of effective drugs for CMT1A still remains as an unmet medical need. In the present study, we assessed the role of the transforming growth factor beta 4 (TGFß4)/Nodal axis in the pathogenesis of CMT1A. First, we identified PMP22 overexpression-induced Nodal expression in Schwann cells, which might be one of the downstream effectors in CMT1A. Administration of Nodal protein at the developmental stage of peripheral nerves induced the demyelinating phenotype in vivo. Second, we further isolated TGFß4 as an antagonist that could abolish Nodal-induced demyelination. Finally, we developed a recombinant TGFß4-fragment crystallizable (Fc) fusion protein, CX201, and demonstrated that its application had promyelinating efficacy in Schwann cells. CX201 administration improved the demyelinating phenotypes of CMT1A mouse models at both pre-symptomatic and post-symptomatic stages. These results suggest that the TGFß4/Nodal axis plays a crucial role in the pathogenesis of CMT1A and might be a potential therapeutic target for CMT1A.

A potential treatment option for advanced non-small cell lung cancer: Three cases.

OBJECTIVE: Recent progress in targeted therapy and immunotherapy has reduced the mortality of advanced-stage patients with non-small cell lung cancer (NSCLC). However, despite advances in treatment, only some patients are eligible for and benefit from genome-targeted therapy, while few patients are ineligible for genome-driven therapy or have limited treatment options due to performance status, comorbidity, and adverse events or rejection of chemotherapy. CLINICAL FEATURES AND OUTCOMES: We report the cases of three patients with advanced NSCLC who were not available to continue conventional anticancer therapy, who were able to maintain progression-free survival (PFS) or disease-free survival (DFS), and who have shown symptom amelioration after treatment with herbal Medicine. Patients were managed only with herbal medicines according to their disease status and symptoms, without conventional anticancer therapy. Two patients with metastatic NSCLC maintained PFS for 19 and 20 months after the discontinuation of chemotherapy, respectively. A patient with locally advanced NSCLC showed no evidence of recurrence for more than 5 years despite an increase in squamous cell carcinoma antigens. These patients had considerable clinical outcomes to maintain relatively long PFS and DFS. CONCLUSION: This study demonstrates the potential treatment option of herbal medicine in inhibiting tumor progression and prolonging PFS and DFS in patients with advanced NSCLC.

Cytokines secreted by mesenchymal stem cells reduce demyelination in an animal model of Charcot-Marie-Tooth disease.

INTRODUCTION: Demyelinating Charcot-Marie-Tooth disease (CMT) is caused by mutations in the genes that encode myelinating proteins or their transcription factors. Our study thus sought to assess the therapeutic effects of cytokines secreted from mesenchymal stem cells (MSCs) on this disease. METHODS: The therapeutic potential of Wharton's jelly MSCs (WJ-MSCs) and cytokines secreted by WJ-MSCs was evaluated on Schwann cells (SCs) exhibiting demyelination features, as well as a mouse model of demyelinating CMT. RESULTS: Co-culture with WJ-MSC protected PMP22-overexpressing SCs from apoptotic cell death. Using a cytokine array, the secretion of growth differentiation factor-15 (GDF-15) and amphiregulin (AREG) was found to be elevated in WJ-MSCs when co-incubated with the PMP22-overexpressing SCs. Administration of both cytokines into trembler-J (Tr-J) mice, an animal model of CMT, significantly enhanced motor nerve conduction velocity compared to the control group. More importantly, this treatment alleviated the demyelinating phenotype of Tr-J mice, as demonstrated by an improvement in the mean diameter and g-ratio of the myelinated axons. CONCLUSIONS: Our findings demonstrated that WJ-MSCs alleviate the demyelinating phenotype of CMT via the secretion of several cytokines. Further elucidation of the underlying mechanisms of GDF-15 and AREG in myelination might provide a robust basis for the development of effective therapies against demyelinating CMT.

A Compound Heterozygous Pathogenic Variant in B4GALNT1 Is Associated With Axonal Charcot-Marie-Tooth Disease.

BACKGROUND AND PURPOSE: Pathogenic variants in B4GALNT1 have been reported to cause hereditary spastic paraplegia 26. This study has revealed that a novel compound heterozygous pathogenic variant in B4GALNT1 is associated with axonal Charcot-Marie-Tooth disease (CMT). METHODS: Whole-exome sequencing (WES) was used to identify the causative factors and characterize the clinical features of a Korean family with sensorimotor polyneuropathy. Functional assessment of the mutant genes was performed using a motor neuron cell line. RESULTS: The WES revealed a compound heterozygous pathogenic variant (c.128dupC and c.451G>A) in B4GALNT1 as the causative of the present patient, a 53-year-old male who presented with axonal sensorimotor polyneuropathy and cognitive impairment without spasticity. The electrodiagnostic study showed axonal sensorimotor polyneuropathy. B4GALNT1 was critical to the proliferation of motor neuron cells. The compensation assay revealed that the pathogenic variants might affect the enzymatic activity of B4GALNT1. CONCLUSIONS: This study is the first to identify a case of autosomal recessive axonal CMT associated with a compound heterozygous pathogenic variant in B4GALNT1. This finding expands the clinical and genetic spectra of peripheral neuropathy.

Influence of FKBP5 Variants and Childhood Trauma on Brain Volume in Non-clinical Individuals.

The present study aimed to investigate the possible influence of childhood trauma and its interaction effect with 10 single-nucleotide polymorphisms (SNPs) of the FK506-binding protein 51 (FKBP5) gene on brain volume in non-clinical individuals. One hundred forty-four non-clinical volunteers (44 men and 100 women) were genotyped with respect to 10 variants (rs9296158, rs3800373, rs1360780, rs9470080, rs4713916, rs4713919, rs6902321, rs56311918, rs3798345, and rs9380528) of FKBP5. Participants underwent magnetic resonance imaging (MRI) scan and psychological assessments such as the childhood Trauma Questionnaire (CTQ), Hospital Anxiety and Depression Scale, rumination response scale, and quality of life assessment instrument. Individuals with the high CTQ score showed enlarged volume of the left orbitofrontal cortex (OFC) if they have childhood trauma-susceptible genotype of FKBP5 rs3800373, rs1360780, rs4713916, rs4713919, rs6902321, and rs3798345 and enlarged volume of the left middle temporal gyrus (MTG) if they have childhood trauma-susceptible genotype of FKBP5 rs3800373, rs1360780, rs4713916, and rs3798345. Among those with the childhood trauma-susceptible genotype, the left OFC and left MTG showed significant negative correlations with positive feelings about life, and the left OFC showed significant positive correlations with negative cognition. This is one of the few studies to identify the volume alteration of the left OFC and the left MTG for the FKBP5 gene-childhood trauma interaction in non-clinical individuals.

Gait parameters as tools for analyzing phenotypic alterations of a mouse model of Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT), a genetically heterogeneous group of diseases in the peripheral nervous system, is characterized by progressive and symmetrical distal weakness resulting in gait abnormality. The necessity of the diagnostic and prognostic biomarkers has been raised for both basic research and clinical practice in CMT. Since biomarkers for animal study of CMT are limited, we evaluated the feasibility of gait parameters as tool for measuring disease phenotype of CMT mouse model. Using a Trembler-J (Tr-J) mouse, a CMT type 1 (CMT1) mouse model, we analyzed kinematic parameters such as angles of hip, knee and ankle (sagittal plane), and spatial parameters including step width and stride length (transverse plane). Regarding of kinematic parameters, Tr-J mice exhibited less plantarflexed ankle during the swing phase and more dorsiflexed ankle at the terminal stance compared to control mice. The range of motion in ankle angle of Tr-J mice was significantly greater than that of control mice. In spatial parameter, Tr-J mice exhibited wider step width compared to control mice. These results are similar to previously reported gait patterns of CMT1 patients. In comparison with other markers such as nerve conduction study and rotarod test, gait parameters dynamically reflected the disease progression of CMT1 mice. Therefore, these data imply that gait parameters can be used as useful tools to analyzed the disease phenotype and progression during preclinical study of peripheral neuropathy such as CMT.

A potential treatment option for elderly non-Hodgkin lymphoma patients with multiple comorbidities: Two case reports and literature review.

Non-Hodgkin lymphoma (NHL) is a heterogeneous lymphoproliferative malignancy. More than half of the NHL cases occur in patients over 65 years of age. As elderly patients have a poor performance status and multiple comorbidities, the use of standard chemotherapy is often limited, leading to poor clinical outcomes and an increasing need for an alternate therapeutic modalities. A 73-year-old man was diagnosed with extranodal NK/T-cell lymphoma concurrently combined with recurrent gastric adenocarcinoma and metastatic prostate cancer. A 79-year-old woman was diagnosed with T-cell and B-cell dual-phenotype NHL on the right chest wall showing tumor thrombosis and multiple enlarged lymph nodes under chronic emphysema with extensive pleural calcification. Both elderly patients had multiple comorbidities and pathologically confirmed non-Hodgkin lymphoma. Both patients achieved tumor responses following anticancer treatment with Korean medicine (KM), suggesting that the extracts of Angelica gigas Nakai and Geopungtang are potential options for treating NHL in elderly patients with multiple comorbidities. Considering the clinical outcomes of KM treatment in the two elderly patients with NHL and multiple comorbidities, this study generates a research hypothesis for future prospective clinical studies in patients with NHL who are ineligible for conventional anticancer therapy.

Altered Cortical Thickness-Based Individualized Structural Covariance Networks in Patients with Schizophrenia and Bipolar Disorder.

Structural covariance is described as coordinated variation in brain morphological features, such as cortical thickness and volume, among brain structures functionally or anatomically interconnected to one another. Structural covariance networks, based on graph theory, have been studied in mental disorders. This analysis can help in understanding the brain mechanisms of schizophrenia and bipolar disorder. We investigated cortical thickness-based individualized structural covariance networks in patients with schizophrenia and bipolar disorder. T1-weighted magnetic resonance images were obtained from 39 patients with schizophrenia, 37 patients with bipolar disorder type I, and 32 healthy controls, and cortical thickness was analyzed via a surface-based morphometry analysis. The structural covariance of cortical thickness was calculated at the individual level, and covariance networks were analyzed based on graph theoretical indices: strength, clustering coefficient (CC), path length (PL) and efficiency. At the global level, both patient groups showed decreased strength, CC and efficiency, and increased PL, compared to healthy controls. In bipolar disorder, we found intermediate network measures among the groups. At the nodal level, schizophrenia patients showed decreased CCs in the left suborbital sulcus and the right superior frontal sulcus, compared to bipolar disorder patients. In addition, patient groups showed decreased CCs in the right insular cortex and the left superior occipital gyrus. Global-level network indices, including strength, CCs and efficiency, positively correlated, while PL negatively correlated, with the positive symptoms of the Positive and Negative Syndrome Scale for patients with schizophrenia. The nodal-level CC of the right insular cortex positively correlated with the positive symptoms of schizophrenia, while that of the left superior occipital gyrus positively correlated with the Young Mania Rating Scale scores for bipolar disorder. Altered cortical structural networks were revealed in patients, and particularly, the prefrontal regions were more altered in schizophrenia. Furthermore, altered cortical structural networks in both patient groups correlated with core pathological symptoms, indicating that the insular cortex is more vulnerable in schizophrenia, and the superior occipital gyrus is more vulnerable in bipolar disorder. Our individualized structural covariance network indices might be promising biomarkers for the evaluation of patients with schizophrenia and bipolar disorder.

Prognostic Value of Functional Assessment of Cancer Therapy-General (FACT-G) in Advanced Non-Small-Cell Lung Cancer Treated with Korean Medicine.

OBJECTIVES: The impact of health-related quality of life (HRQoL) on survival has been investigated in patients with various cancers. Here, we evaluated the prognostic value of HRQoL using the Functional Assessment of Cancer Therapy-General (FACT-G) in advanced non-small-cell lung cancer (NSCLC) patients treated with Korean medicine. METHODS: A retrospective review of medical records and FACT-G scores of patients with advanced NSCLC who received treatment with Korean medicine was conducted. The reliability of the FACT-G was determined using Cronbach's alpha and calculating floor-and-ceiling effects. Correlations between FACT-G scores were estimated using Pearson's correlation analysis. Overall survival was calculated using the Kaplan-Meier method, and the prognostic impact of FACT-G scores and patients' characteristics was evaluated with Cox proportional hazards regression. RESULTS: Of the 165 enrolled patients, 115 (70%) had extrathoracic metastasis and 139 (84%) had undergone prior anticancer treatment. The median overall survival was 10.1 months. The mean FACT-G score was 65.0, and Cronbach's alpha for the FACT-G was 0.917. Age ≥65 years, male sex, smoking history, squamous-cell carcinoma, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≥2, and presence of extrathoracic metastasis were associated with an increased risk of mortality. High FACT-G total scores, physical well-being (PWB), emotional well-being, and functional well-being were associated with prolonged survival. After adjusting for age, sex, smoking history, ECOG-PS, histological type, and presence of extrathoracic metastasis, a high FACT-G total score (hazard ratio (HR): 0.99, p=0.032) and high PWB score (HR: 0.94, p < 0.001) were associated with prolonged survival as independent prognostic factors in patients with advanced NSCLC. CONCLUSION: The FACT-G total score and PWB score as HRQoL measurements were significant prognostic factors for survival in advanced NSCLC patients treated with Korean medicine. This finding implies that the FACT-G can be used in clinical practice as a predictor of survival in patients with advanced NSCLC.

Riemannian classifier enhances the accuracy of machine-learning-based diagnosis of PTSD using resting EEG.

Recently, objective and automated methods for the diagnosis of post-traumatic stress disorder (PTSD) have attracted increasing attention. However, previous studies on machine-learning-based diagnosis of PTSD with resting-state electroencephalogram (EEG) have reported poor accuracies of as low as 60%. Here, a Riemannian geometry-based classifier, the Fisher geodesic minimum distance to the mean (FgMDM), was employed for PTSD classification for the first time. Eyes-closed resting-state EEG data of 39 healthy individuals and 42 PTSD patients were used for the analysis. EEG source activities in 148 cortical regions were parcellated based on the Destrieux atlas, and their covariances were evaluated for each individual. Thirty epochs of preprocessed EEG were employed to calculate source activities. In addition, the FgMDM approach was applied to each EEG source covariance to construct the classifier. For a comparison, linear discriminant analysis (LDA), support vector machine (SVM), and random forest (RF) classifiers employing source band powers and network features as feature candidates were also tested. The FgMDM classifier showed an average classification accuracy of 75.240.80%. In contrast, the maximum accuracies of LDA, SVM, and RF classifiers were 66.54 ± 2.99%, 61.11 ± 2.98%, and 60.99 ± 2.19%, respectively. Our study demonstrated that the diagnostic accuracy of PTSD with resting-state EEG could be significantly improved by employing the FgMDM framework, which is a type of Riemannian geometry-based classifier.

Clinical Implication of Altered Inhibitory Response in Patients with Post-traumatic Stress Disorder: Electrophysiological Evidence from a Go/Nogo Task.

Inhibitory dysfunction is closely associated to post-traumatic stress disorder (PTSD). The present study investigated the neurophysiological evidence for and the brain regions related to inhibitory dysfunction in PTSD. Fifty patients with PTSD and 63 healthy controls (HCs) participated in a Go/Nogo task combined with electroencephalographic recordings. The N2-P3 complexes of event-related potentials (ERPs) elicited during the Nogo condition were compared between groups. Participants underwent structural magnetic resonance imaging to examine cortical volumes and completed questionnaires. Correlations between altered ERPs and cortical volumes of regions of interest as well as psychological symptoms were analysed. Nogo-N2 latencies at five electrode sites (Fz, FCz, Cz, CPz, and Pz) were significantly delayed in patients with PTSD compared to HCs. Nogo-N2 latency had a significant negative correlation with the volume of gyrus in the inferior frontal cortex, orbitofrontal cortex, amygdala, and medial prefrontal cortex. Nogo-N2 latency was significantly and positively correlated with catastrophizing, anxiety, and perceived threat. These findings show inhibitory dysfunction in patients with PTSD, reflected by the delay in Nogo-N2 latencies. They also indicate that Nogo-N2 latencies are associated with smaller cortical volumes responsible for inhibition as well as with major symptoms of PTSD.

Energy efficient sludge solubilization by microwave irradiation under carbon nanotube (CNT)-coated condition.

Microwaves (MW) have great potential for sludge solubilization, and carbon materials can act as good microwave absorbers and heat transfer media because of their high dielectric loss tangent and thermal conductivity. In this study, carbon nanotube-coated MW vessels were developed by preparing a silane-CNT mixture and spray coating. In addition, sludge solubilization by microwave irradiation was performed to evaluate the effects of the CNT-coating at different initial total suspended solid (TSS) concentrations, target temperatures, and MW irradiation times in the uncoated and CNT-coated MW vessels. The sludge solubilization efficiency increased with increasing MW irradiation time and temperature and followed a first-order reaction in both vessels. However, the energy requirement to maintain the temperature was reduced in the CNT-coated MW vessel compared to the uncoated vessel. In addition, the Arrhenius equation revealed the catalytic site in the CNT-coated MW vessel to have a temperature of around 130 °C at an average sludge temperature of 100 °C. The maximum chemical oxygen demand (COD) solubilization and soluble COD (sCOD) increase per MW energy used were 1.64 and 1.67 times higher in the CNT-coated MW vessel than in the uncoated vessel, respectively. The increase in soluble total nitrogen and phosphorus in the CNT-coated MW vessel was attributed to cell wall destruction and intracellular protoplast dissolution, because of the acceleration of the MW thermal effect and high conductivity of CNTs, as well as the MW-induced cell wall and membrane disruption by hot spots on the CNT surface. This suggests that CNTs can be applied to increase the energy efficiency in MW-based pretreatment methods.

Self-Awareness of Psychopathology and Brain Volume in Patients With First Episode Psychosis.

Memory impairment, excessive rumination, and increased interpersonal sensitivity are major characteristics of high psychosis risk or first episode psychosis (FEP). Herein, we investigated the relationship between brain volume and self-awareness of psychopathology in patients with FEP. All participants (FEP: 34 and HCs: 34) completed clinical assessments and the following self-reported psychopathology evaluations: prospective and retrospective memory questionnaire (PRMQ), ruminative response scale (RRS), and interpersonal sensitivity measure (IPSM). Structural magnetic resonance imaging was then conducted. The PRMQ, RRS, and IPSM scores were significantly higher in the FEP group than in the healthy controls (HCs). The volumes of the amygdala, hippocampus, and superior temporal gyrus (STG) were significantly lower in the FEP group than in the HCs. There was a significant group-dependent moderation effect between self-awareness of psychopathology (PRMQ, RRS, and IPSM scores) and right STG (rSTG) volume. In the FEP group, self-awareness of psychopathology was positively associated with rSTG volume, while in the HCs, this correlation was negative. Our results indicate that self-awareness of psychopathology impacts rSTG volume in the opposite direction between patients with FEP and HCs. In patients with FEP, awareness of impairment may induce increases in rSTG brain volume. However, HCs showed decreased rSTG volume when they were aware of impairment.

Prognostic Value of Ferritin-to-Hemoglobin Ratio in Patients with Advanced Non-Small-Cell Lung Cancer.

BACKGROUND: Among commonly used biomarkers that reflect overall health in patients with cancer, hemoglobin is an iron-containing, oxygen-carrying protein in red blood cells, and serum ferritin is an iron-storage protein. This study investigated the ability of the ferritin-to-hemoglobin ratio to predict survival in patients with advanced non-small-cell lung cancer (NSCLC). METHODS: The medical records of patients with pathologically confirmed advanced NSCLC were retrospectively reviewed. The ferritin level, hemoglobin level, and ferritin-to-hemoglobin ratio at the initiation of treatment were investigated. After descriptive analysis of the ferritin-to-hemoglobin ratio, the optimal diagnostic cutoff value for survival was determined using receiver operating characteristic analysis. After dichotomizing patients according to the optimal cutoff value, the prognostic effect of the ferritin-to-hemoglobin ratio was assessed. Overall survival (OS) was calculated using Kaplan-Meier analysis and compared using log-rank tests. Cox proportional hazards regression was used to evaluate the prognostic effect with respect to survival. RESULTS: Of the enrolled patients, 91.3% had stage IV NSCLC, 42.0% had an Eastern Cooperative Oncology Group-performance status (ECOG-PS) score of 2, and 56.5% previously underwent systemic chemotherapy. The median OS of enrolled patients was 11.5 months. The range of the ferritin-to-hemoglobin ratio was 0.6-294.2, and the optimal cutoff value of the ferritin-to-hemoglobin ratio for survival was 13.0 (sensitivity, 58.5%; specificity, 80.0%; area under the curve = 0.68; P = 0.004). The median OS of patients with a low ferritin-to-hemoglobin ratio (<13.0) was 19.7 months, whereas that of patients with a high ferritin-to-hemoglobin ratio (≥13.0) was 8.5 months (P < 0.001). After eliminating confounding factors such as age, sex, ECOG-PS, histologic type, and C-reactive protein level, a high ferritin-to-hemoglobin ratio was significantly associated with poor survival. The multivariate proportional hazards model revealed that the ferritin-to-hemoglobin ratio was an independent prognostic marker for survival (hazard ratio, 1.91; 95% confidence interval, 1.27-2.88; P = 0.002). CONCLUSION: The ferritin-to-hemoglobin ratio, a potential parameter of tumor progression, was a significant prognostic factor for OS, with a direct correlation to survival time in patients with advanced NSCLC.

Influence of childhood trauma and brain-derived neurotrophic factor Val66Met polymorphism on posttraumatic stress symptoms and cortical thickness.

Interaction between childhood trauma and genetic factors influences the pathophysiology of posttraumatic stress disorder (PTSD). This study examined the interaction effect of childhood trauma and brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on PTSD symptoms and brain cortical thickness. A total of 216 participants (133 healthy volunteers and 83 PTSD patients) were recruited. T1-weighted structural magnetic resonance imaging, BDNF rs6265 genotyping through blood sampling, and clinical assessments including the childhood trauma questionnaire (CTQ) and posttraumatic stress disorder Checklist (PCL) were performed. A moderated regression analysis, two-way multivariate analysis of covariance, and correlation analysis were conducted. An interaction between the CTQ and the BDNF polymorphism significantly influenced PTSD symptom severity. In fact, people with rs6265 Val/Val genotype and higher CTQ scores showed higher PCL scores. Additionally, this interaction was significant on both left fusiform and transverse temporal gyri thickness. Furthermore, the thickness of both brain regions was significantly correlated with psychological symptoms including depression, anxiety, rumination, and cognitive emotion regulation methods; yet this was mainly observed in people with the Val/Val genotype. The interaction between childhood trauma and BDNF polymorphism significantly influences both PTSD symptoms and cortical thickness and the Val/Val genotype may increase the risk in Korean population.

Mismatch Negativity and Cortical Thickness in Patients With Schizophrenia and Bipolar Disorder.

INTRODUCTION: Mismatch negativity (MMN) is a measure of automatic neurophysiological brain processes for detecting unexpected sensory stimuli. This study investigated MMN reduction in patients with schizophrenia and bipolar disorder and examined whether cortical thickness is associated with MMN, for exploratory purposes. METHODS: Electroencephalograms were recorded in 38 patients with schizophrenia, 37 patients with bipolar disorder, and 32 healthy controls (HCs) performing a passive auditory oddball paradigm. All participants underwent T1 structural magnetic resonance imaging scanning to investigate the cortical thickness of MMN-generating regions. Average MMN amplitudes from the frontocentral electrodes were analyzed. RESULTS: Patients with schizophrenia and bipolar disorder exhibited significantly reduced MMN amplitude compared with HCs. In bipolar disorder, we found intermediate MMN amplitude among the groups. Average MMN and cortical thickness of the right superior temporal gyrus (STG) were significantly negatively correlated in patients with schizophrenia. In patients with bipolar disorder, average MMN was significantly correlated with cortical thickness of the left anterior cingulate cortex and the right STG. MMN showed negative correlations with social and occupational functioning in schizophrenia, and with the Korean auditory verbal learning test for delayed recall in bipolar disorder. CONCLUSIONS: MMN reduction was associated with cortical thinning in frontal and temporal areas in patients, particularly with an auditory verbal hallucination-related region in schizophrenia and emotion-related regions in bipolar disorder. MMN was associated with functional outcomes in schizophrenia, whereas it was associated with neurocognition in bipolar disorder.

From Neurons to Social Beings: Short Review of the Mirror Neuron System Research and Its Socio-Psychological and Psychiatric Implications.

The mirror neuron system (MNS) is a brain network activated when we move our body parts and when we observe the actions of other agent. Since the mirror neuron's discovery in research on monkeys, several studies have examined its network and properties in both animals and humans. This review discusses MNS studies of animals and human MNS studies related to high-order social cognitions such as emotion and empathy, as well as relations between MNS dysfunction and mental disorders. Finally, these evidences are understood from an evolutionary perspective.

Prognostic Significance of Host-related Biomarkers for Survival in Patients with Advanced Non-Small Cell Lung Cancer.

OBJECTIVE: This study identified host-related prognostic biomarkers for survival in patients with advanced non-small cell lung cancer (NSCLC). METHODS: This study was based on the retrospective review of the medical records of 135 patients with pathologically confirmed advanced NSCLC. The host-related biomarkers assessed in this study that reflected patient condition included hemoglobin (Hb) levels; platelet (PLT), neutrophil, lymphocyte, and monocyte counts; and ferritin concentrations. The overall survival (OS) was calculated by Kaplan-Meier analysis and compared using log-rank tests. Univariate and multivariate analyses of Cox proportional hazards regression were used to evaluate the prognostic impact for survival. RESULTS: Of the enrolled patients, 91.1% had stage IV NSCLC, 42.2% had ECOG-PS scores of 2, and 57% had undergone multiple rounds of prior systemic therapy. The prognostic factors included low Hb concentration (men: Hb < 13 g/dL, women: Hb < 12 g/dL; p = 0.046), increased neutrophil count (> 7,700 cells/µL; p < 0.001), decreased lymphocyte count (≤ 1500 cells/µL; p = 0.011), increased monocyte count (> 800 cells/µL; p < 0.001), and high ferritin level (men: > 200 ng/mL, women: > 150 ng/mL; p < 0.001), which were associated with poor OS and increased hazard of mortality. The multivariate proportional hazards model revealed that lymphocyte count, monocyte count, and ferritin level were independent host-related prognostic biomarkers for survival. Increased monocyte count (HR, 3.15; 95% CI, 1.64-6.04; p < 0.001) and high ferritin level (HR, 1.81; 95% CI, 1.24-2.64; p = 0.002) were significantly associated with poor survival, whereas increased lymphocyte count (HR, 0.57; 95% CI, 0.40-0.83; p = 0.004) showed prolonged survival. CONCLUSION: Immune factors, such as lymphocyte and monocyte counts, as well as serum ferritin levels, are significant host-related prognostic biomarkers for survival with direct relevance to survival time in patients with advanced NSCLC.

Neural correlates of the eye dominance effect in human face perception: the left-visual-field superiority for faces revisited.

Faces are processed best when they are presented in the left visual field (LVF), a phenomenon known as LVF superiority. Although one eye contributes more when perceiving faces, it is unclear how the dominant eye (DE), the eye we unconsciously use when performing a monocular task, affects face processing. Here, we examined the influence of the DE on the LVF superiority for faces using event-related potentials. Twenty left-eye-dominant (LDE group) and 23 right-eye-dominant (RDE group) participants performed the experiments. Face stimuli were randomly presented in the LVF or right visual field (RVF). The RDE group exhibited significantly larger N170 amplitudes compared with the LDE group. Faces presented in the LVF elicited N170 amplitudes that were significantly more negative in the RDE group than they were in the LDE group, whereas the amplitudes elicited by stimuli presented in the RVF were equivalent between the groups. The LVF superiority was maintained in the RDE group but not in the LDE group. Our results provide the first neural evidence of the DE's effects on the LVF superiority for faces. We propose that the RDE may be more biologically specialized for face processing.

Improved physicochemical properties and hepatic protection of Maillard reaction products derived from fish protein hydrolysates and ribose.

High amounts of waste products generated from fish-processing need to be disposed of despite their potential nutritional value. A variety of methods, such as enzymatic hydrolysis, have been developed for these byproducts. In the current study, we investigated the physicochemical, biological and antioxidative properties of fish protein hydrolysates (FPH) conjugated with ribose through the Maillard reaction. These glycated conjugates of FPH (GFPH) had more viscous rheological properties than FPH and exhibited higher heat, emulsification and foaming stability. They also protected liver HepG2 cells against t-BHP-induced oxidative stress with enhanced glutathione synthesis in vitro. Furthermore, it was shown that GFPH induced upregulation of phase II enzyme expression, such as that of HO-1 and γ-GCL, via nuclear translocation of Nrf2 and phosphorylation of ERK. Taken together, these results demonstrate the potential of GFPH for use as a functional food ingredient with improved rheological and antioxidative properties.