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Mesenchymal stem cells, cardiac-derived progenitor cells, embryonic stem cells, induced pluripotent stem cells (iPSCs), and iPSC-derived cardiomyocytes release exosomes that have been shown to have cardioprotective, immunomodulatory, and reparative effects. Herein, we summarize the regulation roles of miRNAs and exosomes in cardiac stem cells.The dynamic balance between ubiquitination and deubiquitination is a key mechanism that regulates protein degradation and maintains cell protein homeostasis. Ubiquitin-specific peptidase 13 (USP13), a deubiquitinase (DUB), regulates various physiological and pathological processes, including cancer. A previous study reported that high USP13 mRNA expression confers poor prognosis in gastric cancer (GC). However, the biological function of USP13 in GC remains unknown. Here, we revealed that USP13 expression was upregulated in GC tissue samples compared to noncancerous tissues. USP13-positive expression was associated with poor differentiation, high invasiveness, and advanced tumor stage. Notably, upregulated USP13 expression was closely correlated with the reduced survival of GC patients. We also confirmed increased USP13 expression in GC cell lines. USP13 knockdown prominently suppressed MGC-803 cell migration and invasion. Conversely, USP13 overexpression markedly enhanced SGC-7901 cell motility. Furthermore, USP13 positively regulates the epithelial-mesenchymal transition (EMT) of GC cells. Interestingly, USP13 remarkably enhanced Snail protein expression but did not affect its mRNA levels in GC cells. We confirmed a positive correlation between USP13 and Snail expression in GC tissues. Mechanistically, USP13 knockdown promoted Snail degradation, which could be blocked by the proteasome inhibitor MG132. USP13 interacted with Snail to deubiquitinate and stabilize Snail in GC cells. Finally, Snail knockdown significantly blocked USP13-induced SGC-7901 cell migration and invasion. In conclusion, USP13 overexpression was frequently detected in GC and contributed to the EMT and metastasis of GC by stabilizing Snail.

In gastric cancer (GC), extracapsular growth (ECG) pattern of lymph node metastases is associated with decreased overall survival rates compared to intracapsular lymph node metastases (ICG). Epithelial-to-mesenchymal transition (EMT) plays a pivotal role in hematogenous metastatic spread. Aim of the present study was to analyze if EMT related genes are involved in the growth pattern of lymph node metastases in GC.

Out of our prospective database with 529 patients who underwent surgical resection for GC between 2002 and 2014 forty lymph node positive patients were identified (20 ECG, 20 ICG). The expression of 84 EMT-associated genes were analyzed by RT2 Profiler PCR Array (n=20). Results were validated by Real-Time PCR (n=20).

GC with ECG showed differently expressed EMT related genes. GC leading to ECG showed an upregulation of three and downregulation of eleven genes. Those differences, however, could not be confirmed in PCR analysis.

This study demonstrates that EMT related genes are not responsible for the different growth patterns of lymph node metastases in GC. Bemcentinib research buy Further studies are required to evaluate the underlying mechanisms of ECG in GC as it might provide a potential therapeutic target for this subgroup of more aggressive tumors in the future.

This study demonstrates that EMT related genes are not responsible for the different growth patterns of lymph node metastases in GC. Further studies are required to evaluate the underlying mechanisms of ECG in GC as it might provide a potential therapeutic target for this subgroup of more aggressive tumors in the future.

To identify semiologic features of automatisms correlating to different seizure onset zones (SOZ).

In total, 204 seizures from 74 patients with either oral or manual automatisms were assessed. Patients were divided into four groups depending on the SOZ into frontal, posterior, neocortical temporal, and mesial temporal cortex groups. A k-means analysis was applied on 11 semiologic features on a multi-criteria scale. Then, the resulting clinical patterns were correlated with the SOZs determined by presurgical anatomy-electroclinical data (25 cases with stereo-EEG).

Four clinical patterns of automatisms with different accompanying symptoms were identified. The clinical features of clusters 1 and 4 were mostly found in temporal epilepsy whereas clusters 2 and 3 were more frequent in extratemporal epilepsy. Cluster 1 was significantly correlated with mesial temporal lobe epilepsy (p=.017) and was characterised by aura, postictal confusion, short automatisms delay. Cluster 3 included 1/3 patients with frontal lobe epilepsy and was characterised by emotionality. Cluster 4 was related to neocortical temporal lobe epilepsy and characterised by dystonia and short automatism delay (p=.011).

The distinct semiologic patterns of automatisms may provide information which may allow clinicians to define the SOZs. These findings could improve diagnostic accuracy and surgical outcome.

The distinct semiologic patterns of automatisms may provide information which may allow clinicians to define the SOZs. These findings could improve diagnostic accuracy and surgical outcome.

For epilepsy patients with drug-resistant, unresectable epilepsy, vagus nerve stimulation (VNS) is an option for seizure control. Approximately 40-70% of patients will achieve ≥50% seizure reduction with VNS. New closed loop VNS models detect ictal tachycardia and responsively stimulate the vagus nerve. The effectiveness of closed loop VNS compared to traditional VNS for pediatric epilepsy is unknown.

An 11-year retrospective electronic medical record review at Children's Hospital of Pittsburgh was performed. Patients with drug-resistant epilepsy who underwent VNS implantation were included. Patients were divided into groups based on VNS model traditional versus closed loop. link2 Those who transitioned from traditional to closed loop VNS were excluded. Given potential for selection bias, propensity scores matching was utilized to compare traditional to closed loop VNS patients. Patients with focal versus generalized epilepsy were also separately analyzed. The primary outcome was "VNS response", defined as at lially among generalized epilepsy patients. Neither model of VNS allows patients to reduce antiseizure medication quantity after two years.

Among pediatric patients with drug-resistant epilepsy, closed loop VNS trends towards a higher rate of VNS response after two years of treatment, especially among generalized epilepsy patients. Neither model of VNS allows patients to reduce antiseizure medication quantity after two years.

To report the effect of the ketogenic diet (KD) on non-convulsive status epilepticus (NCSE) due to Angelman syndrome (AS) in two members of a large Georgian family affected by a novel frameshift variant in the UBE3A gene (NM_000462.3).

We evaluated two members of this family who were affected with clinical and EEG features of AS. Clinical history with special emphasis on development, seizure type, frequency, and treatment was reviewed. Routine and long-term video EEG monitoring were conducted, particularly during NCSE. A non-fasting inpatient KD protocol was implemented using blended food orally with full administration of 41 (fat to non-fat) ratio. Urine ketone bodies (KBs), measured with urine ketone acetone strips readings, reached 150mg/dL in both patients.

Patients had characteristic signs of AS and presented with epilepsy between the age of 2-4 years. As methylation tests were negative, next generation sequencing disclosed a c.2365del variant. link3 For both, NCSE was revealed by cognitive deterioration and did not respond to anti-seizure medication. As recommended, IV pyridoxine, benzodiazepines, and valproic acid were administered, but without success. For both patients, NCSE resolved on the second-third day of KD initiation, before the appearance of ketonuria and resulting in improved communication, mood and sleep.

KD is safe and effective for the treatment of NCSE due to AS. Resolution before the appearance of ketone bodies points to a possible mechanism of action of KD.

KD is safe and effective for the treatment of NCSE due to AS. Resolution before the appearance of ketone bodies points to a possible mechanism of action of KD.

Numerous research studies indicate that stuttering is associated with increased risk for social anxiety disorder (SAD). Interpretation bias is one of four cognitive biases thought to maintain symptoms associated with SAD. Interpretation bias occurs when one evaluates social situations as more negative than they actually are. The purpose of this study was to investigate if adults who do and do not stutter interpret positive, ambiguous, mildly negative, and profoundly negative social situations similarly, or-if like individuals with SAD-adults who stutter exhibit negative interpretation biases.

Forty-eight adults who stutter and 42 age-and gender-matched adults who do not stutter participated. Participants completed the Fear of Negative Evaluation (FNE) and were assigned to one of four groups adults who stutter with high FNE (AWS-High), adults who stutter with low FNE (AWS-Low), adults who do not stutter with high FNE (AWNS-High), and adults who do not stutter with low FNE (AWNS-Low). All participants compl stutter with low and high FNE interpret social situations similarly, and that no group demonstrated a negative interpretation bias consistent with what is observed in adults with SAD. The interpretations provided by each group were appropriate to the specific scenarios being evaluated.

Results suggested that adults who do and do not stutter with low and high FNE interpret social situations similarly, and that no group demonstrated a negative interpretation bias consistent with what is observed in adults with SAD. The interpretations provided by each group were appropriate to the specific scenarios being evaluated.

To determine whether there is a correlation between obesity-related variants and regional brain volumes.

Based on a mixed linear model (MLM), we analyzed the association between 1,498 obesity-related SNPs in the GWAS Catalog and 164 regional brain volumes from 29,420 participants (discovery cohort N=19,997, validation cohort N=9,423) in UK Biobank. The statistically significant brain regions in association analysis were classified into 6 major neural networks (dopamine (DA) motive system, central autonomic network (CAN), cognitive emotion regulation, visual object recognition network, auditory object recognition network, and sensorimotor system). We summarized the association between obesity-related variants (metabolically healthy obesity variants, metabolically unhealthy obesity variants, and unclassified obesity-related variants) and neural networks.

From association analysis, we determined that 17 obesity-related SNPs were associated with 51 regional brain volumes. Several single SNPs (e.g., rs1310735), and high mobility group protein AT-hook 2 (HMGA2 protein).

In summary, we found that obesity-related variants were associated with different brain volume measures. On the basis of the multiple SNPs, we found that metabolically healthy and unhealthy obesity-related SNPs were associated with different brain neural networks. Based on our enrichment analysis, modifications of the 5-HT4 pathway might be a promising therapeutic strategy for obesity.

In summary, we found that obesity-related variants were associated with different brain volume measures. On the basis of the multiple SNPs, we found that metabolically healthy and unhealthy obesity-related SNPs were associated with different brain neural networks. Based on our enrichment analysis, modifications of the 5-HT4 pathway might be a promising therapeutic strategy for obesity.