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Objective: The sympathetic–parasympathetic (or axo–axonal) interaction mechanism mediated that neurogenic relaxation, which was dependent on norepinephrine (NE) releases from sympathetic nerve terminal and acts on β2‐adrenoceptor of parasympathetic nerve terminal, has been reported. As NE is a weak β2‐adrenoceptor agonist, there is a possibility that synaptic NE is converted to epinephrine by phenylethanolamine‐N‐methyltransferase (PNMT) and then acts on the β2‐adrenoceptors to induce neurogenic vasodilation. Methods: Blood vessel myography technique was used to measure relaxation and contraction responses of isolated basilar arterial rings of rats. Results: Nicotine‐induced relaxation was sensitive to propranolol, guanethidine (an adrenergic neuronal blocker), and Nω‐nitro‐l‐arginine. Nicotine‐ and exogenous NE‐induced vasorelaxation was partially inhibited by LY‐78335 (a PNMT inhibitor), and transmural nerve stimulation depolarized the nitrergic nerve terminal directly and was not inhibited by LY‐78335; it then induced the release of nitric oxide (NO). Epinephrine‐induced vasorelaxation was not affected by LY‐78335. However, these vasorelaxations were completely inhibited by atenolol (a β1‐adrenoceptor antagonist) combined with ICI‐118,551 (a β2‐adrenoceptor antagonist). Conclusions: These results suggest that NE may be methylated by PNMT to form epinephrine and cause the release of NO and vasodilation. These results provide further evidence supporting the physiological significance of the axo–axonal interaction mechanism in regulating brainstem vascular tone. [ABSTRACT FROM AUTHOR]

The goal of stroke rehabilitation is to establish a robust protocol for patients to live independently in community. Firstly, we examined the impact of 3 hybridized transcranial direct current stimulation (tDCS)-mirror therapy interventions on activities of daily life (ADL) in stroke patients. Secondly, we explored the underlying therapeutic mechanisms with theory-driven electroencephalography (EEG) indexes in the alpha band. This was achieved by identifying the unique contributions of alpha power in motor production to ADL in relation to the premotor cortex (PMC), primary cortex (M1), and Sham tDCS with mirror therapy. The results showed that, although post-intervention ADL improvement was comparable among the three tDCS groups, one of the EEG indexes differentiated the interventions. Neural-behavioral correlation analyses revealed that different types of ADL improvements consistently corresponded with alpha power in the temporal lobe exclusively in the PMC tDCS group (all rs > 0.39). By contrast, alterations in alpha power in the central-frontal region were found to vary, with ADL primarily in the M1 tDCS group (r = −0.6 or 0.7), with the benefit depending on the complexity of the ADL. In conclusion, this research suggested two potential therapeutic mechanisms and demonstrated the additive benefits of introducing theory-driven neural indexes in explaining ADL. [ABSTRACT FROM AUTHOR]

BackgroundApparent diffusion coefficients (ADCs) obtained with diffusion-weighted imaging (DWI) are highly valuable for the detection and staging of prostate cancer and for assessing the response to treatment. However, DWI suffers from significant anatomic distortions and susceptibility artifacts, resulting in reduced accuracy and reproducibility of the ADC calculations. The current methods for improving the DWI quality are heavily dependent on software, hardware, and additional scan time. Therefore, their clinical application is limited. An accelerated ADC generation method that maintains calculation accuracy and repeatability without heavy dependence on magnetic resonance imaging scanners is of great clinical value.ObjectivesWe aimed to establish and evaluate a supervised learning framework for synthesizing ADC images using generative adversarial networks.MethodsThis prospective study included 200 patients with suspected prostate cancer (training set: 150 patients; test set #1: 50 patients) and 10 healthy volunteers (test set #2) who underwent both full field-of-view (FOV) diffusion-weighted imaging (f-DWI) and zoomed-FOV DWI (z-DWI) with b-values of 50, 1,000, and 1,500 s/mm2. ADC values based on f-DWI and z-DWI (f-ADC and z-ADC) were calculated. Herein we propose an ADC synthesis method based on generative adversarial networks that uses f-DWI with a single b-value to generate synthesized ADC (s-ADC) values using z-ADC as a reference. The image quality of the s-ADC sets was evaluated using the peak signal-to-noise ratio (PSNR), root mean squared error (RMSE), structural similarity (SSIM), and feature similarity (FSIM). The distortions of each ADC set were evaluated using the T2-weighted image reference. The calculation reproducibility of the different ADC sets was compared using the intraclass correlation coefficient. The tumor detection and classification abilities of each ADC set were evaluated using a receiver operating characteristic curve analysis and a Spearman correlation coefficient.ResultsThe s-ADCb1000 had a significantly lower RMSE score and higher PSNR, SSIM, and FSIM scores than the s-ADCb50 and s-ADCb1500 (all P < 0.001). Both z-ADC and s-ADCb1000 had less distortion and better quantitative ADC value reproducibility for all the evaluated tissues, and they demonstrated better tumor detection and classification performance than f-ADC.ConclusionThe deep learning algorithm might be a feasible method for generating ADC maps, as an alternative to z-ADC maps, without depending on hardware systems and additional scan time requirements.

Summary: Increased aerobic glycolysis is a hallmark of cancer metabolism. How cancer cells coordinate glucose metabolism with extracellular glucose levels remains largely unknown. Here, we report that coactivator-associated arginine methyltransferase 1 (CARM1 or PRMT4) signals glucose availability to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and suppresses glycolysis in liver cancer cells. CARM1 methylates GAPDH at arginine 234 (R234), inhibiting its catalytic activity. Glucose starvation leads to CARM1 upregulation, further inducing R234 hypermethylation and GAPDH inhibition. The re-expression of wild-type GAPDH, but not of its methylation-mimetic mutant, sustains glycolytic levels. CARM1 inhibition increases glycolytic flux and glycolysis. R234 methylation delays tumor cell proliferation in vitro and in vivo. Compared with normal tissues, R234 is hypomethylated in malignant clinical hepatocellular carcinoma samples. Notably, R234 methylation positively correlates with CARM1 expression in these liver cancer samples. Our findings thus reveal that CARM1-mediated GAPDH methylation is a key regulatory mechanism of glucose metabolism in liver cancer. : GAPDH is a critical enzyme in glycolysis. Zhong et al. find that CARM1 methylates GAPDH at R234 and inhibits its activity in an AMPK-dependent manner. R234 methylation inhibits glycolysis and proliferation of liver cancer cell lines. In hepatocellular carcinoma patient samples, GADPH R234 is hypomethylated, and there is a positive correlation between CARM1 levels and R234 methylation. Keywords: GAPDH, CARM1, arginine methylation, coenzyme affinity, glycolysis, AMPK, nutrient sensing, Warburg effect, metabolic reprogramming, liver cancer

To report two novel TTN variants associated with fetal recessive titinopathy, thereby broadening the range of TTN variants that can lead to titinopathy. Clinical information on the fetus and parents was gathered, and genomic DNAs were extracted from the fetal tissue and family members' peripheral blood samples. Exome sequencing on fetal DNA was performed and following bioinformatics analysis, the suspected pathogenic variants were confirmed through Sanger sequencing. Prenatal ultrasound performed at 29 weeks of gestation revealed hydrops fetalis, decreased fetal movements, multiple joint contractures and polyhydramnios. Intrauterine fetal death was noted in the third trimester. Exome sequencing revealed compound heterozygous variants in the TTN gene: a paternally inherited allele c.101227C>T (p.Arg33743Ter) and a maternally inherited c.104254C>T (p.Gln34752Ter) allele. These variants have not been previously reported and are evaluated to be likely pathogenic according to the American College of Medical Genetics and Genomics guidelines. We report a fetus with hydrops fetalis and arthrogryposis multiplex congenita associated with a compound heterozygote in the TTN gene. Our report broadens the clinical and genetic spectrum associated with the TTN‐related conditions. Key points: What is already known about this topic? Fetal hydrops, fetal hypokinesia/akinesia and cardiac dysfunction can be associated with biallelic truncating variants in exons encoding the M‐band region of titin. What does this study add? We describe a case of fetal recessive titinopathy associated with a compound heterozygote in the TTN gene.This broadens the clinical and genetic spectrum of TTN‐related conditions. [ABSTRACT FROM AUTHOR]

Background: We determined the feasibility of, and tissue response to silicone-covered biodegradable magnesium- and plastic-stent insertion into the esophagus in rabbits. Methods: The mechanical compression–recovery characteristics and degradation behaviors of the magnesium stent were investigated in vitro . A total of 45 rabbits were randomly divided into a magnesium- ( n = 15) and a plastic- ( n = 15) stent group, and underwent stent insertion into the lower third of the esophagus under fluoroscopic guidance; a control group ( n = 15) did not undergo the intervention. Esophagography was performed at 1, 2, and 4 weeks. Five rabbits in each group were euthanized at each time point for histological examination. Results: Silicone-covered magnesium stents showed similar radial force to plastic stents ( p > 0.05). The magnesium stents degraded rapidly in an acidic solution, but 90.2% ± 3.1% of the residual mass was maintained after a 2-week degradation in a solution with a pH of 4.0. All stent insertions were well tolerated. Magnesium stents migrated in six rabbits (one at 1 week, one at 2 weeks and four at 4 weeks), and plastic stents migrated in three rabbits (one at 2 weeks and two at 4 weeks; p > 0.05). Esophageal wall remodeling (thinner epithelial and smooth muscle layers) was similar in both stented groups ( p > 0.05), and the esophagus wall was found to be significantly thinner in the stented groups than in the control group ( p < 0.05). Esophageal injury and collagen deposition following stent insertion were similar and did not differ from the control group ( p > 0.05). Conclusions: Esophageal silicone-covered magnesium stents provided reliable support for at least 2 weeks, with acceptable migration rates and without causing severe injury or tissue reaction compared with plastic stents.

The present study aimed to investigate the acute effects and the mechanism of ketamine on nicotine-induced relaxation of the corpus cavernosum (CC) in mice. This study measured the intra-cavernosal pressure (ICP) of male C57BL/6 mice and the CC muscle activities using an organ bath wire myograph. Various drugs were used to investigate the mechanism of ketamine on nicotine-induced relaxation. Direct ketamine injection into the major pelvic ganglion (MPG) inhibited MPG-induced increases in ICP. D-serine/L-glutamate-induced relaxation of the CC was inhibited by MK-801 (N-methyl-D-aspartate (NMDA) receptor inhibitor), and nicotine-induced relaxation was enhanced by D-serine/L-glutamate. NMDA had no effect on CC relaxation. Nicotine-induced relaxation of the CC was suppressed by mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist), lidocaine, guanethidine (an adrenergic neuronal blocker), Nw-nitro-L-arginine (a non-selective nitric oxide synthase inhibitor), MK-801, and ketamine. This relaxation was almost completely inhibited in CC strips pretreated with 6-hydroxydopamine (a neurotoxic synthetic organic compound). Ketamine inhibited cavernosal nerve neurotransmission via direct action on the ganglion and impaired nicotine-induced CC relaxation. The relaxation of the CC was dependent on the interaction of the sympathetic and parasympathetic nerves, which may be mediated by the NMDA receptor. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of percutaneous aspiration thrombectomy (PAT) for infrainguinal arterial thromboembolism in patients undergoing endovascular recanalization (EVR) and to investigate the predictors for thromboembolic complications.In total, 23 patients (23 limbs) who underwent PAT for thromboembolism (PAT group, PG) during EVR and 237 patients (302 limbs) who underwent successful EVR without thromboembolic complications (control group, CG) were enrolled. Immediate post-operation and follow-up outcomes were compared between the two groups. Multivariate analysis was performed to identify the predictors of thromboembolic complications. Technical success of PAT was defined as achievement of

Importance: The Mini-Clinical Evaluation Exercise (Mini-CEX) is highly recommended for assessing interns' performance. Objective: To develop a pediatric occupational therapy–specific Mini-CEX and examine its psychometrics. Design: Stage 1 had a retrospective design; Stage 2 had a prospective design. Setting: Pediatric occupational therapy unit in a hospital in Taiwan. Participants: Thirty-four occupational therapy interns were evaluated with the Mini-CEX (physician version), and 57 were evaluated with the occupational therapy–specific Mini-CEX. Outcomes and Measures: The occupational therapy–specific Mini-CEX was developed with seven items on a 9-point scale categorized into three levels (unsatisfactory, satisfactory, highly satisfactory). Results: In Stage 1, the frequency of Mini-CEX (physician version) items receiving a rating of not applicable ranged from 1.9% to 88.1%. In Stage 2, the frequency of occupational therapy–specific Mini-CEX items receiving a rating of not applicable ranged from 3.5% to 31.6%. With the theme of evaluation taken into consideration, the frequency of not-applicable ratings was 0% to 8.8%. For the occupational therapy–specific Mini-CEX, content validity (item-level content validity index = 1, scale-level content validity index = 1) and internal consistency (Cronbach's α =.93) were excellent. The interns' scores on the second evaluation were significantly higher than those on their first evaluation, indicating good discriminant validity. Conclusions and Relevance: The occupational therapy–specific Mini-CEX appears to be reliable and valid, and it is appropriate for evaluating interns' skills and attitudes in pediatric occupational therapy practice. What This Article Adds: The results support the development of the occupational therapy–specific Mini-CEX and its application in pediatric internship training. The results of this study support the development of the occupational therapy–specific Mini-CEX and its application in evaluating interns' skills and attitudes in pediatric occupational therapy practice. [ABSTRACT FROM AUTHOR]