Comparison of Capillary Architecture between Slow and Fast Muscles in Rats Using a Confocal Laser Scanning Microscope

The skeletal muscle is classified into 2 types, slow oxidative or fast glycolytic muscle. For further characterization, we investigated the capillary architecture in slow and fast muscles. The rat soleus and extensor digitorum longus (EDL) muscles were used as representatives of slow and fast muscles, respectively. To investigate capillary density, sections of both types of muscle were stained with alkaline phosphatase;the soleus muscle showed more intense reactivity, indicating that it had a denser capillary structure than the EDL muscle. We then injected fluorescent contrast medium into samples of both muscle types for light and confocal-laser microscopic evaluation. The capillary density and capillary-to-fiber ratio were significantly higher, and the course of the capillaries was more tortuous, in the soleus muscle than in the EDL muscle. Capillary coursed more tortuously in the soleus than in the EDL muscle. Succinate dehydrogenase (SDH) activity, an indicator of mitochondrial oxidative capacity, and vascular endothelial growth factor (VEGF) expression were also significantly higher in the soleus muscle. Thus, we conclude that slow oxidative muscle possess a rich capillary structure to provide demanded oxygen, and VEGF might be involved in the formation and/or maintenance of this highly capillarized architecture.</p

Effect of cognitive function on jumping to conclusion in patients with schizophrenia

The “jumping to conclusion” (JTC) bias is related to the formation and maintenance of delusions. Higher JTC bias can be based on both neurocognitive dysfunction and social cognitive dysfunction in patients with schizophrenia. The aim of this study was to assess the relationship between JTC bias, neurocognition, and social cognition in patients with schizophrenia. A total of 22 patients with schizophrenia and 21 controls participated in this study. Neurocognition and social cognition were assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) and Social Cognition Screening Questionnaire (SCSQ), respectively. The JTC bias and the decision confidence were assessed using the beads task. The patients were classified into the JTC group (with higher JTC bias; n = 10) and JTC-non group (n = 12). The JTC group scored significantly lower on verbal memory, working memory, and motor speed sub-scores of BACS than the JTC-non group. No difference in social cognition was observed between the two groups. The decision confidence was predicted by metacognition, which is an SCSQ sub-score. Similarly to the patients, the controls were classified into the JTC group (higher JTC bias; n = 9) and the JTC-non group (n = 12). There were no significant differences in neurocognition and social cognition between the control JTC and JTC-non groups. The present results indicated that JTC bias is related to neurocognition and decision confidence is related to social cognition in patients with schizophrenia. These findings may bridge the gaps between psychotic symptom and cognitive dysfunction in schizophrenia

Jumping to conclusion bias in adolescents with ASD

Background and Purpose: Jumping to conclusion (JTC)—a cognitive bias in thinking processes—leads to drawing conclusions based on little information, and could be related to psychosis and paranoia. While it has recently been pointed out that it could accompany the autism spectrum disorder (ASD), no interventions targeting this bias in adolescents with ASD have been reported. Therefore, this exploratory study investigated the effects of a group social cognition program on JTC bias in adolescents with ASD. Patients and Methods : Group rehabilitation using social cognition and interaction training (SCIT) was conducted for 12- to 18-year-old adolescents with ASD. An SCIT program comprehensively targets social cognitive functions, including interventions for JTC bias, and examines changes before and after the SCIT intervention, social cognitive functioning tasks, and subjective quality of life (QOL). Results : Thirteen adolescents with ASD participated in this program ; 10 (76.9%) stayed through it. The proportion of participants with JTC bias decreased significantly before and after SCIT (before : 7 / 10 ; after : 1 / 10 ; p = 0.041), and subjective QOL increased significantly (p = 0.014). Conclusion : The results show that a group social cognition program with a JTC bias approach improves the JTC bias and increases subjective QOL in adolescents with ASD

Detection of RBM15-MKL1 Fusion Was Useful for Diagnosis and Monitoring of Minimal Residual Disease in Infant Acute Megakaryoblastic Leukemia

Acute megakaryocytic leukemia (AMKL) with t(1;22)(p13;q13) is a distinct category of myeloid leukemia by WHO classification and mainly reported in infants and young children. Accurate diagnosis of this type of AMKL can be difficult, because a subset of patients have a bone marrow (BM) blast percentage of less than 20% due to BM fibrosis. Therefore, it is possible that past studies have underestimated this type of AMKL. We present here the case of a 4-month-old female AMKL patient who was diagnosed by presence of the RBM15-MKL1 (OTT-MAL) fusion transcript by RT-PCR. In addition, we monitored RBM15-MKL1 fusion at several time points as a marker of minimal residual disease (MRD), and found that it was continuously negative after the first induction chemotherapy even by nested RT-PCR. Detection of the RBM15-MKL1 fusion transcript thus seems to be useful for accurate diagnosis of AMKL with t(1;22)(p13;q13). We recommend that the RBM15-MKL1 fusion transcript be analyzed for all suspected AMKL in infants and young children. Furthermore, monitoring of MRD using this fusion transcript would be useful in treatment of AMKL with t(1;22)(p13;q13)

Mitochondrial intermediate peptidase is a novel regulator of sirtuin-3 activation by caloric restriction

Sirtuin-3 (SIRT3) regulates mitochondrial quality and is involved in the anti-ageing and pro-longevity actions of caloric restriction (CR). Here, we show that CR upregulates the mature form of SIRT3 and mitochondrial intermediate peptidase (MIPEP), a mitochondrial signal peptidase (MtSPase), in white adipose tissue. We also demonstrate that upregulation of mature SIRT3 is dependent on MIPEP in 3T3-L1 cells, suggesting that MIPEP may contribute to the maintenance of mitochondrial quality during CRvia activation of SIRT3. This novel mechanism of SIRT3 activation through MIPEP facilitates the elucidation of additional molecular pathways of CR

統合失調症におけるSalience Network機能障害、抑うつ気分、および主観的QOLの因果関係を評価する構造方程式モデリングアプローチ : 独立成分分析による安静時ｆMRI研究

Purpose: Quality of life (QOL) is an important clinical outcome for patients with schizophrenia, and recent studies have focused on subjective QOL. We evaluated the causal relationship between psychosocial aspect of subjective QOL, symptoms, cognitive functions, and salience network (SN) dysfunction in schizophrenia using structural equation modeling (SEM). Patients and methods: We performed a cross-sectional study of 21 patients with symptomatically stabilized schizophrenia and 21 age-, sex-, and education level-matched healthy controls who underwent resting-state functional magnetic resonance imaging. We evaluated SN dysfunction in schizophrenia using independent component analysis (ICA). We rated participant psychopathology using the Positive and Negative Syndrome Scale (PANSS), the Brief Assessment of Cognition in Schizophrenia (BACS), and the Calgary Depression Scale for Schizophrenia (CDSS). We rated psychosocial aspect of subjective QOL using the Schizophrenia Quality of Life Scale (SQLS) psychosocial subscale. We applied SEM to examine the relationships between SN dysfunction, PANSS positive and negative scores, CDSS total scores, BACS composite scores, and SQLS psychosocial subscale scores. Results: In second-level analysis after group ICA, patient group had significant lower right pallidum functional connectivity (FC) within the SN than the controls did (Montreal Neurological Institute [MNI] [x y z] = [22 -2 -6]) (p = 0.027, family-wise error [FWE] corrected). In SEM, we obtained a good fit for an SEM model in which SN dysfunction causes depressed mood, which in turn determines psychosocial aspect of subjective QOL (chi-squared p = 0.9, root mean square error of approximation (RMSEA) < 0.001, comparative fit index [CFI] = 1.00, and standardized root mean square residual [SRMR]= 0.020). Conclusion: We found a continuous process by which SN dysfunction causes depressed moods that determine psychosocial aspect of subjective QOL in schizophrenia. This is the first report that offers a unified explanation of functional neuroimaging, symptoms, and outcomes. Future studies combining neuroimaging techniques and clinical assessments would elucidate schizophrenia’s pathogenesis

統合失調症患者において否定的、肯定的自己認知は主観的QOLを予測する

Purpose: Recently, cognitive variables such as negative and positive self-belief and thoughts have attracted much attention because they are associated with functional outcomes and quality of life (QOL). However, it is unclear how cognitive variables affect subjective and objective QOL. This study aimed to investigate the relationship of negative and positive self-belief and thoughts with subjective and objective QOL. Participants and methods: Thirty-six people with schizophrenia participated in this study. Subjective and objective QOL were assessed with the Schizophrenia Quality of Life Scale (SQLS) and Quality of Life Scale (QLS), respectively. Neurocognitive function was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Clinical symptoms were assessed with the Positive and Negative Syndrome Scale and Calgary Depression Scale for Schizophrenia. Side effects were assessed with the Drug-induced Extrapyramidal Symptoms Scale (DIEPSS). Negative and positive self-belief and thoughts were assessed with the Defeatist Performance Belief Scale and Automatic Thoughts Questionnaire-Revised. A generalized linear model was tested, with subjective and objective QOL as the response variable and symptoms, neurocognitive function, and cognitive variables that were significantly correlated with subjective and objective QOL as explanatory variables. Results: In the schizophrenia group, the common objects score on the QLS was predicted by the composite BACS score, and the total QLS score was predicted by the DIEPSS score. Motivation and Energy, Psychosocial, and Symptoms and Side effects scores on the SQLS were predicted by depression and by negative automatic thought (NAT) and positive automatic thought (PAT). Conclusion: Our results indicated that key targets for improving objective and subjective QOL in people with schizophrenia are side effects, neurocognitive function, depression, and NAT and PAT

Effect of cognitive function on jumping to conclusion in patients with schizophrenia

The “jumping to conclusion” (JTC) bias is related to the formation and maintenance of delusions. Higher JTC bias can be based on both neurocognitive dysfunction and social cognitive dysfunction in patients with schizophrenia. The aim of this study was to assess the relationship between JTC bias, neurocognition, and social cognition in patients with schizophrenia. A total of 22 patients with schizophrenia and 21 controls participated in this study. Neurocognition and social cognition were assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) and Social Cognition Screening Questionnaire (SCSQ), respectively. The JTC bias and the decision confidence were assessed using the beads task. The patients were classified into the JTC group (with higher JTC bias; n = 10) and JTC-non group (n = 12). The JTC group scored significantly lower on verbal memory, working memory, and motor speed sub-scores of BACS than the JTC-non group. No difference in social cognition was observed between the two groups. The decision confidence was predicted by metacognition, which is an SCSQ sub-score. Similarly to the patients, the controls were classified into the JTC group (higher JTC bias; n = 9) and the JTC-non group (n = 12). There were no significant differences in neurocognition and social cognition between the control JTC and JTC-non groups. The present results indicated that JTC bias is related to neurocognition and decision confidence is related to social cognition in patients with schizophrenia. These findings may bridge the gaps between psychotic symptom and cognitive dysfunction in schizophrenia

Physiological mouse brain Abeta levels are not related to the phosphorylation state of threonine-668 of Alzheimer's APP.

Amyloid-beta peptide species ending at positions 40 and 42 (Abeta40, Abeta42) are generated by the proteolytic processing of the Alzheimer's amyloid precursor protein (APP). Abeta peptides accumulate in the brain early in the course of Alzheimer's disease (AD), especially Abeta42. The cytoplasmic domain of APP regulates intracellular trafficking and metabolism of APP and its carboxyl-terminal fragments (CTFalpha, CTFbeta). The role of protein phosphorylation in general, and that of the phosphorylation state of APP at threonine-668 (Thr668) in particular, has been investigated in detail by several laboratories (including our own). Some investigators have recently proposed that the phosphorylation state of Thr668 plays a pivotal role in governing brain Abeta levels, prompting the current study