A Japanese Patient with Hereditary Myopathy with Early Respiratory Failure Due to the p.P31732L Mutation of Titin

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Effects of integrated hospital treatment on the default mode, salience, and frontal-parietal networks in anorexia nervosa: A longitudinal resting-state functional magnetic resonance imaging study.

The psychopathology of patients with anorexia nervosa has been hypothesized to involve inappropriate self-referential processing, disturbed interoceptive awareness, and excessive cognitive control, including distorted self-concern, disregard of their own starvation state, and extreme weight-control behavior. We hypothesized that the resting-state brain networks, including the default mode, salience and frontal-parietal networks, might be altered in such patients, and that treatment might normalize neural functional connectivity, with improvement of inappropriate self-cognition. We measured resting-state functional magnetic resonance images from 18 patients with anorexia nervosa and 18 healthy subjects before and after integrated hospital treatment (nourishment and psychological therapy). The default mode, salience, and frontal-parietal networks were examined using independent component analysis. Body mass index and psychometric measurements significantly improved after treatment. Before treatment, default mode network functional connectivity in the retrosplenial cortex and salience network functional connectivity in the ventral anterior insula and rostral anterior cingulate cortex were decreased in anorexia nervosa patients compared with those in controls. Interpersonal distrust was negatively correlated with salience network functional connectivity in the rostral anterior cingulate cortex. Default mode network functional connectivity in the posterior insula and frontal-parietal network functional connectivity in the angular gyrus were increased in anorexia nervosa patients compared with those in controls. Comparison between pre- and post-treatment images from patients with anorexia nervosa exhibited significant increases in default mode network functional connectivity in the hippocampus and retrosplenial cortex, and salience network functional connectivity in the dorsal anterior insula following treatment. Frontal-parietal network functional connectivity in the angular cortex showed no significant changes. The findings revealed that treatment altered the functional connectivity in several parts of default mode and salience networks in patients with anorexia nervosa. These alterations of neural function might be associated with improvement of self-referential processing and coping with sensations of discomfort following treatment for anorexia nervosa

Gut Dysbiosis in Patients with Anorexia Nervosa.

Anorexia nervosa (AN) is a psychological illness with devastating physical consequences; however, its pathophysiological mechanism remains unclear. Because numerous reports have indicated the importance of gut microbiota in the regulation of weight gain, it is reasonable to speculate that AN patients might have a microbial imbalance, i.e. dysbiosis, in their gut. In this study, we compared the fecal microbiota of female patients with AN (n = 25), including restrictive (ANR, n = 14) and binge-eating (ANBP, n = 11) subtypes, with those of age-matched healthy female controls (n = 21) using the Yakult Intestinal Flora-SCAN based on 16S or 23S rRNA-targeted RT-quantitative PCR technology. AN patients had significantly lower amounts of total bacteria and obligate anaerobes including those from the Clostridium coccoides group, Clostridium leptum subgroup, and Bacteroides fragilis group than the age-matched healthy women. Lower numbers of Streptococcus were also found in the AN group than in the control group. In the analysis based on AN subtypes, the counts of the Bacteroides fragilis group in the ANR and ANBP groups and the counts of the Clostridium coccoides group in the ANR group were significantly lower than those in the control group. The detection rate of the Lactobacillus plantarum subgroup was significantly lower in the AN group than in the control group. The AN group had significantly lower acetic and propionic acid concentrations in the feces than the control group. Moreover, the subtype analysis showed that the fecal concentrations of acetic acid were lower in the ANR group than in the control group. Principal component analysis confirmed a clear difference in the bacterial components between the AN patients and healthy women. Collectively, these results clearly indicate the existence of dysbiosis in the gut of AN patients

The BBB disruption was restored after adding GM6001 or a neutralizing anti-VEGF antibody to the sera from relapsing MS patients.

<p>(A)–(J) The effects of TNF-α, IFN-γ, IL-17 or VEGF neutralizing antibodies or a matrix- metalloproteinases (MMPs) inhibitor, GM6001, on the amount of tight junction proteins in TY09 cells after exposure to the sera from SPMS or RRMS-R patients was determined by a Western blot analysis. (K)–(N) Each bar graph reflects the combined densitometry data from each independent experiment (mean±SEM, SPMS n = 6, RRMS-R n = 4). (M) In patients with RRMS-R, preincubation with a VEGF neutralizing antibody or GM6001 increased the amount of claudin-5 protein in TY09 cells. Part 2 (O) The TEER value of the TY09 cells significantly increased after incubation with the sera from RRMS-R patients that had been pretreated with an anti-VEGF neutralizing antibody or GM 6001 (mean±SEM, n = 6). SPMS: conditioned medium containing a 10% concentration of serum from a SPMS patient diluted with non-conditioned DMEM containing 10% FBS; SPMS+TNF-α Ab: conditioned medium with 10% SPMS sera pretreated with a TNF-α neutralizing antibody; SPMS+IFN-γ Ab: conditioned medium with 10% SPMS sera pretreated with an IFN-γ neutralizing antibody; SPMS+IL-17 Ab: conditioned medium with 10% SPMS sera pretreated with an IL-17 neutralizing antibody; SPMS+VEGF Ab: conditioned medium with 10% SPMS sera pretreated with a VEGF neutralizing antibody; SPMS+GM6001: conditioned medium with 10% SPMS sera pretreated with GM6001; RRMS-R: conditioned medium containing a 10% concentration of serum from a RRMS-R patient diluted with non-conditioned DMEM containing 10% FBS; RRMS-R+TNF-α Ab: conditioned medium with 10% RRMS-R sera pretreated with a TNF-α neutralizing antibody; RRMS-R+IFN-γ Ab: conditioned medium with 10% RRMS-R sera pretreated with an IFN-γ neutralizing antibody; RRMS-R+IL-17 Ab: conditioned medium with 10% RRMS-R sera pretreated with an IL-17 neutralizing antibody; RRMS-R+VEGF Ab: conditioned medium with 10% RRMS-R sera pretreated with a VEGF neutralizing antibody; RRMS-R+GM6001: conditioned medium with 10% RRMS-R sera pretreated with GM6001.</p

The sera from relapsing MS increased the autocrine MMP-2/9 secretion in TY09 cells.

<p>(A)–(C) The VEGF or MMP-2/9 concentrations were analyzed in the sera from patients with SPMS, RRMS-R or RRMS-S, or from healthy control subjects. The bars indicate the mean of each group. No significant differences were observed between the four groups. (D)–(F) The amounts of VEGF or MMP-2/9 by TY09 cells after exposure to sera from SPMS, RRMS-R or RRMS-S patients. (G)–(I) Each bar graph reflects the combined densitometry data from each independent experiment (mean ± SEM, SPMS n = 6, RRMS-R n = 6, RRMS-S n = 6). The amounts of MMP-2 and MMP-9 protein in the TY09 cells were significantly increased after exposure to the sera from RRMS-R patients, although it did not change after exposure to the sera from SPMS or RRMS-S patients. Control: non-conditioned DMEM containing 20% FBS; SPMS: conditioned medium with 10% serum from an SPMS patient diluted with non-conditioned DMEM containing 10% FBS; RRMS-R: conditioned medium with a 10% concentration of serum from an RRMS-R patient diluted with non-conditioned DMEM containing 10% FBS; RRMS-S: conditioned medium with a 10% concentration of serum from an RRMS-S patient diluted with non-conditioned DMEM containing 10% FBS.</p

The effects of MS patients' sera on the tight junction proteins and adhesion molecules in TY09 cells.

<p>(A)–(D) The changes in the amounts of claudin-5, occludin and VCAM-1 in human brain microvascular endothelial cells, named “TY09 cells”, were determined after exposure to the sera from patients in the relapse phase of MS (RRMS-R), the stable phase of RRMS (RRMS-S) or secondary progressive MS (SPMS), or from healthy controls, as determined by a Western blot analysis. (E)(F)(G) Each bar graph reflects the combined densitometry data from each independent experiment (mean ± SEM, SPMS n = 8, RRMS-R n = 6, RRMS-S n = 9, Normal n = 6). (E)(F) The amount of claudin-5 protein in TY09 cells was significantly decreased after the exposure to sera from SPMS or RRMS-R patients, and the amount of occludin protein in TY09 cells was significantly reduced after exposure to sera from SPMS patients, whereas the amounts of the claudin-5 and occludin proteins were not significantly affected by exposure to sera from RRMS-S patients or healthy controls. (G) The amount of VCAM-1 was significantly increased after exposure to sera from RRMS-R, RRMS-S or SPMS patients (H) The TEER value of BMECs was significantly decreased after exposure to RRMS-R or SPMS sera, but was not influenced by exposure to sera from RRMS-S patients or healthy controls (mean±SEM, SPMS n = 8, RRMS-R n = 6, RRMS-S n = 9, Normal n = 6). Control: non-conditioned DMEM containing 20% FBS; SPMS: conditioned medium with 10% serum from an SPMS patient diluted with non-conditioned DMEM containing 10% FBS; RRMS-R: conditioned medium with a 10% concentration of serum from an RRMS-R patient diluted with non-conditioned DMEM containing 10% FBS; RRMS-S: conditioned medium with a 10% concentration of serum from an RRMS-S patient diluted with non-conditioned DMEM containing 10% FBS; Normal: conditioned medium with 10% serum from a healthy control diluted with non-conditioned medium of DMEM containing 10% FBS.</p