Synthesis of [1]Benzothieno[3,2-b][1]benzothiophenes through Iodine-Mediated Sulfur Insertion Reaction.

[1]Benzothieno[3,2-b][1]benzothiophenes (BTBTs) are important molecules that have been extensively studied as high-performance organic field-effect transistors (OFETs). Therefore, it is important to develop a simple synthetic method for these molecules. In this paper, a synthetic method to obtain the BTBTs from 2-arylbenzo[b]thiophenes and elemental sulfur, in which two C-S bonds are formed at once, is described. In this method, molecular iodine plays a very important role as an additive. The role of iodine is discussed in the presumed reaction pathways.

Impact of an enhanced recovery protocol in frail patients after intracorporeal urinary diversion.

OBJECTIVE: To determine whether an enhanced recovery after surgery (ERAS) protocol enhances bowel recovery and reduces postoperative ileus (POI) in both non-frail and frail patients after robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC). PATIENTS AND METHODS: This retrospective cohort study included 186 patients (104 with and 82 without ERAS) who underwent iRARC between 2012 and 2023. 'Frail' patients was defined as those with a low Geriatric-8 questionnaire score (≤13). The primary outcomes were postoperative bowel recovery and the incidence of POI. Secondary outcomes included length of stay (LOS), 30- and 90-day complications, 90-day readmission rate, and POI predictors. RESULTS: The ERAS group exhibited a significantly shorter LOS, early bowel recovery, a lower POI rate, fewer 90-day high-grade complications, and fewer 90-day readmissions than the non-ERAS group in the entire cohort. Non-frail patients in the ERAS group had a lower rate of POI (7.1% vs. 22.1%; P = 0.008), whereas ERAS did not reduce POI in frail patients (44.1% vs. 36.6%; P = 0.50). In the multivariate analysis, ERAS was associated with a reduced risk of POI in both the entire cohort (odds ratio [OR] 0.39, P = 0.01) and in non-frail patients (OR 0.24, P = 0.01), whereas ERAS was not likely to reduce POI (OR 1.14, P = 0.70) in frail patients. Prehabilitation was identified as a favourable predictor of POI. CONCLUSIONS: The ERAS protocol did not reduce POI in frail patients after iRARC, although it enhanced bowel recovery and reduced POI in non-frail patients. Prehabilitation for frail patients might reduce POI.

Synthesis of [1]Benzothieno[2,3-b][1]benzothiophenes from 3-Arylbenzo[b]thiophenes through Iodine-Mediated Sulfur Insertion Reaction.

The reaction of 3-arylbenzo[b]thiophenes and elemental sulfur to obtain [1]benzothieno[2,3-b][1]benzothiophenes (BTBTs) is reported. The addition of molecular iodine is essential for the reaction. In previous reactions that used 1,1-diarylethylenes as the starting material, side products that were difficult to separate were generated. The present reaction does not produce such side products and is therefore advantageous for obtaining BTBTs in high yield and purity.

Prevalence and genetic diversity in bovine parechovirus infecting Japanese cattle.

The first bovine parechovirus (Bo_ParV) was reported in 2021, and currently, only two nearly complete genome sequences of Bo_ParV are available. In this study, we detected Bo_ParVs in 10 out of 158 bovine fecal samples tested using real-time RT-PCR, and Bo_ParVs were isolated from three of these samples using MA104 cells. Analysis of the P1 region revealed that Bo_ParVs shared high pairwise amino acid sequence similarity (≥ 95.7% identity), suggesting antigenic similarity among Bo_ParVs, whereas nucleotide sequence identity values (≥ 84.8%) indicated more variability. A recombination breakpoint was identified in the 2B region, which may influence the evolution of this virus.

Four-dimensional flow magnetic resonance imaging visualizes reverse vortex pattern and energy loss increase in left bundle branch block.

AIMS: This study aimed to investigate the intraventricular blood flow pattern of patients with left bundle branch block (LBBB) using four-dimensional flow magnetic resonance imaging (4D-flow MRI). METHODS AND RESULTS: We performed 4D-flow MRI for 16 LBBB patients (LBBB group) and 16 propensity score-matched patients with a normal QRS duration (non-LBBB group). The energy loss (EL) in the left ventricle was evaluated. In both groups, blood flow from the mitral valve to the apex of the heart and left ventricular (LV) outflow tract during LV diastole were observed. Vortices were also observed in both groups. There were two patterns of vortices: unidirectional clockwise rotation and counterclockwise rotation taking place from the mid-diastole to the systole (reverse pattern). The reverse pattern was observed significantly more frequently in the LBBB group (LBBB 94% vs. non-LBBB 19%, P < 0.001). The interobserver agreement for the streamline analysis was good (kappa = 0.68). The maximum EL was significantly higher in the LBBB group [LBBB 12 (11-15) mW vs. non-LBBB 8.0 (6.2-9.7) mW, P < 0.001]. CONCLUSION: Left bundle branch block patients may suffer from inefficient LV haemodynamics reflected by non-physiological counterclockwise vortices and increased EL. Thus, the shape of the vortices and EL in the left ventricle can serve as markers of LV mechanical dyssynchrony in LBBB patients and could be investigated as predictors of response to cardiac resynchronization therapy.

Usefulness of P-wave peak time as an electrocardiographic parameter in predicting left ventricular diastolic dysfunction in patients with mitral regurgitation.

INTRODUCTION: Conventional Doppler measurements have limitations in predicting left ventricular diastolic dysfunction (LVDD) in patients with mitral regurgitation (MR). Recently, electrocardiographic P-wave peak time (PWPT) has been proposed as a parameter of detecting LVDD. This study aimed to evaluate the association between PWPT and left ventricular end-diastolic pressure (LVEDP) in patients with MR. METHODS: We performed echocardiography and cardiac catheterization in 82 patients with moderate or severe MR. We classified patients into two groups: low LVEDP group (L-LVEDP) (LVEDP <16 mmHg, n = 40) and high LVEDP group (H-LVEDP) (LVEDP ≥16 mmHg, n = 42). We evaluated LVDD and PWPT based on echocardiographic and electrocardiographic findings in both groups. RESULTS: The PWPT in lead II (PWPTII ) was significantly longer in patients in the H-LVEDP group than in those in the L-LVEDP group (67 vs. 47 ms, p < .001). Using correlation analysis, LVEDP was positively correlated with PWPTII (r = .577, p < .001). Using multivariate analysis, PWPTII was found to be an independent predictor of increased LVEDP (95% CI: 0.1030-0.110; p < .001). Using receiver operating characteristic (ROC) curve analysis, the optimal cutoff value of PWPTII for predicting elevated LVEDP was 58.9 ms, with a sensitivity of 80.0% and a specificity of 73.8% (area under curve: 0.809, 95% CI: 0.713-0.905). CONCLUSION: To the best of our knowledge, this is the first study to assess the effect of a significant valvular disease on PWPT in lead II. These findings suggest that prolonged PWPTII may be an independent predictor of increased LVEDP in patients with moderate or severe MR.

Amygdalohippocampal Area Neurons That Project to the Preoptic Area Mediate Infant-Directed Attack in Male Mice.

Male animals may show alternative behaviors toward infants: attack or parenting. These behaviors are triggered by pup stimuli under the influence of the internal state, including the hormonal environment and/or social experiences. Converging data suggest that the medial preoptic area (MPOA) contributes to the behavioral selection toward the pup. However, the neural mechanisms underlying how integrated stimuli affect the MPOA-dependent behavioral selection remain unclear. Here we focus on the amygdalohippocampal area (AHi) that projects to MPOA and expresses oxytocin receptor, a hormone receptor mediating social behavior toward pups. We describe the activation of MPOA-projection AHi neurons in male mice by social contact with pups. Input mapping using the TRIO method reveals that MPOA-projection AHi neurons receive prominent inputs from several regions, including the thalamus, hypothalamus, and olfactory cortex. Electrophysiological and histologic analysis demonstrates that oxytocin modulates inhibitory synaptic responses on MPOA-projection AHi neurons. In addition, AHi forms the excitatory monosynapse to MPOA, and pharmacological activation of MPOA-projection AHi neurons enhances only aggressive behavior, but not parental behavior. Interestingly, this promoted behavior was related to social experience in male mice. Collectively, our results identified a presynaptic partner of MPOA that can integrate sensory input and hormonal state, and trigger pup-directed aggression.SIGNIFICANCE STATEMENT The medial preoptic area (MPOA) plays critical roles in parental behavior, such as motor control, motivation, and social interaction. The MPOA projects to multiple brain regions, and these projections contribute to several neural controls in parental behavior. In contrast, how inputs to MPOA are regulated by social and environmental information is poorly understood. In this study, we focus on the amygdalohippocampal area (AHi) that connects to MPOA and expresses oxytocin receptor. We demonstrate the disruption of the expression of parental behavior triggered by the activation of MPOA-projection AHi neurons. This behavior may be regulated not only by oxytocin but also by neural input from several regions.

The usefulness of a delivery catheter system for right ventricular "true" septal pacing.

Right ventricular (RV) septum is an alternate site for the placement of RV lead tip instead of RV apex. Recent studies have demonstrated that less than half of the RV leads targeted for septal implantation are placed on the RV septum using a conventional stylet system; new guiding catheter systems have become available for RV lead placement. This study aimed to investigate the usefulness of the delivery catheter system in lead placement on the RV septum when compared with the stylet system. We retrospectively evaluated 198 patients who underwent fluoroscopically guided pacemaker implantation with RV leads targeted to be placed in the RV septum and in whom computed tomography was incidentally and subsequently performed. A delivery catheter was used in 16 patients, and a stylet in 182 patients. The primary endpoint of this study was the success rate of RV lead placement on the RV septum. The proportion of RV lead placement on the RV septum was higher in the delivery catheter group than in the stylet group (100% vs. 44%; p < 0.001). In the stylet group, the lead tips were placed at the hinge in 92 cases (51%) and on the free wall in 9 cases (5%). Paced QRS duration was narrower in the delivery catheter group than in the stylet group (128 ± 16 vs. 150 ± 21 ms, p < 0.01). The delivery catheter system designated for pacing leads may aid in selecting RV septal sites and achieve good physiologic ventricular activation.

Impact of Hydrostatic Pressure Variations Caused by Height Differences in Supine and Prone Positions on Fractional Flow Reserve Values in the Coronary Circulation.

OBJECTIVES: To examine the influence of hydrostatic pressure on fractional flow reserve (FFR) in vivo. BACKGROUND: Systematic differences in FFR values have been observed previously in the left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA). It has been suggested that as the hydrostatic pressure variations caused by the height differences between the catheter tip (mean aortic pressure (Pa)) and pressure-wire sensor (mean distal intracoronary pressure (Pd)) are small, intracoronary pressure need not be corrected. METHODS: Resting Pd/Pa and FFR values in 23 patients (27 lesions) were measured and compared in supine and prone positions. These values were corrected by hydrostatic pressure influenced by height levels and compared. Height differences between Pa and Pd were calculated using coronary computed tomography angiographies. RESULTS: In LAD, resting Pd/Pa and FFR values were significantly higher in the prone position than in the supine position (0.97 ± 0.05 vs 0.89 ± 0.04, P < 0.001 (resting Pd/Pa); 0.81 ± 0.09 vs 0.72 ± 0.07, P < 0.001 (FFR)). Conversely, in LCX and RCA, these values were significantly lower in the prone position (LCX: 0.93 ± 0.03 vs 0.98 ± 0.03, P < 0.001 (resting Pd/Pa); 0.84 ± 0.05 vs 0.89 ± 0.04, P < 0.001 (FFR); RCA: 0.91 ± 0.04 vs 0.98 ± 0.03, P=0.005 (resting Pd/Pa); 0.78 ± 0.07 vs 0.84 ± 0.07, P=0.019 (FFR)). FFR values corrected by hydrostatic pressure showed good correlations in the supine and prone positions (R 2 = 0.948 in LAD; R 2 = 0.942 in LCX; R 2 = 0.928 in RCA). CONCLUSIONS: Hydrostatic pressure variations due to height levels influence intracoronary pressure measurements and largely affect resting Pd/Pa and FFR, which might have caused systematic differences in FFR values between the anterior and posterior coronary territories.

Human mitotic chromosomes consist predominantly of irregularly folded nucleosome fibres without a 30-nm chromatin structure.

How a long strand of genomic DNA is compacted into a mitotic chromosome remains one of the basic questions in biology. The nucleosome fibre, in which DNA is wrapped around core histones, has long been assumed to be folded into a 30-nm chromatin fibre and further hierarchical regular structures to form mitotic chromosomes, although the actual existence of these regular structures is controversial. Here, we show that human mitotic HeLa chromosomes are mainly composed of irregularly folded nucleosome fibres rather than 30-nm chromatin fibres. Our comprehensive and quantitative study using cryo-electron microscopy and synchrotron X-ray scattering resolved the long-standing contradictions regarding the existence of 30-nm chromatin structures and detected no regular structure >11 nm. Our finding suggests that the mitotic chromosome consists of irregularly arranged nucleosome fibres, with a fractal nature, which permits a more dynamic and flexible genome organization than would be allowed by static regular structures.

Assembly and disassembly dynamics of the cyanobacterial periodosome.

In vitro incubation of three Kai proteins, KaiA, KaiB, and KaiC, with ATP induces a KaiC phosphorylation cycle that is a potential circadian clock pacemaker in cyanobacterium Synechococcus elongatus PCC 7942. The Kai proteins assemble into large heteromultimeric complexes (periodosome) to effect a robust oscillation of KaiC phosphorylation. Here, we report real-time measurements of the assembly/disassembly dynamics of the Kai periodosome by using small-angle X-ray scattering and determination of the low-resolution shapes of the KaiA:KaiC and KaiB:KaiC complexes. Most previously identified period-affecting mutations could be mapped to the association interfaces of our complex models. Our results suggest that the assembly/disassembly processes are crucial for phase entrainment in the early synchronizing stage but are passively driven by the phosphorylation status of KaiC in the late oscillatory stage. The Kai periodosome is assembled in such a way that KaiA and KaiB are recruited to a C-terminal region of KaiC in a phosphorylation-dependent manner.

Accumulation of endocrine disrupting chemicals (EDCs) in the polychaete Paraprionospio sp. from the Yodo River mouth, Osaka Bay, Japan.

This study presents the levels of endocrine disrupting chemicals (EDCs) accumulated by Paraprionospio sp. from the Yodo River mouth, Osaka Bay. Since high concentrations of nonylphenol (NP), bisphenol A (BP), octylphenol (OP), 17ß-estradiol (E2), and estrone (E1) have been measured in sediment from Osaka Bay, some bioaccumulation could be expected particularly in benthic animals. EDCs were analysed in Paraprionospio sp., a dominant benthic species in Osaka Bay. The results showed that Paraprionospio sp. had accumulated varying concentrations (wet weight; w.w.) of NP at 1,460-4,410 ng/g; BP at 22.5-39.6 ng/g; OP at 18.9-45.4 ng/g; E2 at 0.89-4.35 ng/g; and E1 at 0.06-2.50 ng/g. Accumulation of NP and OP were highest among the samples gathered in summer (July 2008), while concentrations of BP, E2, and E1 did not much differs within 3 years. EDC levels in Paraprionospio sp. were apparently greater than those in sediments showing bioaccumulation.

Gamified exercise for the distal upper extremity in people with post-stroke hemiparesis: feasibility study on subjective perspectives during daily continuous training.

INTRODUCTION: Dose (number of repetitions) has been suggested as a key element in the effectiveness of rehabilitation exercises to promote motor recovery of the hemiparetic upper limb. However, rehabilitation exercises tend to be monotonous and require significant motivation to continue, making it difficult to increase the exercise dose. To address this issue, gamification technology has been implemented in exercises to promote self-engagement for people with hemiparesis in continuing monotonous repetitive movements. This study aimed to investigate how subjective perspectives, specifically enjoyability, motivation to continue, and expectancy of effectiveness, change through continuous daily exercise using a developed gamified exercise system. MATERIALS AND METHOD: Ten people with stroke suffering upper limb dysfunction underwent daily gamified exercise for seven days. The gamified exercise consisted of an electromyography (EMG)-controlled operating system that enabled users to play virtual games using repetitive finger movements. The participants performed conventional self-exercise on the same day as the control exercise, and rated their subjective perspectives on both exercises on a numerical rating scale on each exercise day. RESULTS: Ratings for enjoyability and motivation to continue consistently showed significantly higher scores for the gamified exercise than for conventional self-exercise on all exercise days. A similar trend was observed in the ratings for the expectancy of effectiveness. No changes over time were found in any of the ratings throughout the exercise period. CONCLUSIONS: Exercise using the developed EMG-controlled gamified system may have the potential to maintain motivation and enjoyment in people with stroke to continue monotonous repetitive finger movements.

Although dose (number of repetitions) has been suggested as a key element in the effectiveness of rehabilitation exercises to promote motor recovery of the hemiparetic upper limb, rehabilitation exercises tend to be monotonous and require significant motivation to continue.Gamification technology has been implemented in exercises to promote self-engagement for people with hemiparesis in continuing monotonous repetitive movements.Exercises using the developed EMG-controlled gamified system may have the potential to maintain motivation and enjoyment in people with stroke to continue monotonous repetitive finger movements.

Short- and long-term performance of risk calculation tools for mortality in patients with acute coronary syndrome.

Background: The mortality rate of acute coronary syndrome (ACS) remains high. Therefore, patients with ACS should undergo early risk stratification, for which various risk calculation tools are available. However, it remains uncertain whether the predictive performance varies over time between risk calculation tools for different target periods. This study aimed to compare the predictive performance of risk calculation tools in estimating short- and long-term mortality risks in patients with ACS, while considering different observation periods using time-dependent receiver operating characteristic (ROC) analysis. Methods: This study included 404 consecutive patients with ACS who underwent coronary angiography at our hospital from March 2017 to January 2021. The ACTION and GRACE scores for short-term risk stratification purposes and CRUSADE scores for long-term risk stratification purposes were calculated for all participants. The participants were followed up for 36 months to assess mortality. Using time-dependent ROC analysis, we evaluated the area under the curve (AUC) of the ACTION, CRUSADE, and GRACE scores at 1, 6, 12, 24, and 36 months. Results: Sixty-six patients died during the observation periods. The AUCs at 1, 6, 12, 24, and 36 months of the ACTION score were 0.942, 0.925, 0.889, 0.856, and 0.832; those of the CRUSADE score were 0.881, 0.883, 0.862, 0.876, and 0.862; and those of the GRACE score 0.949, 0.928, 0.888, 0.875, and 0.860, respectively. Conclusions: The ACTION and GRACE scores were excellent risk stratification tools for mortality in the short term. The prognostic performance of each risk score was almost similar in the long term, but the CRUSADE score might be a superior risk stratification tool in the longer term than 3 years.

Bioaccumulation of dietary endocrine disrupting chemicals (EDCs) by the polychaete, Perinereis nuntia.

To investigate the biomagnification factor (BMF) of EDCs by the polychaete, Perinereis nuntia, organisms were exposed to EDCs through their diet. BMF values ranged from 0.001 to 0.028 indicating that EDCs were not biomagnified. Elimination rates were (0.20-0.25 day(-1)) and were higher than uptake rate (0.0003-0.003 day(-1)) verifying that EDCs were not biomagnified by P. nuntia due to their fast elimination. The calculated half-life of each EDC in this study varies from 2.76 to 3.45 days. Overall, the findings from this study demonstrated that the studied EDCs are not biomagnified in P. nuntia but exposure does occur from the diet.

Mechanism of Drug-Eluting Stent Thrombosis Diagnosed by Histopathological Evaluation of Directional Coronary Atherectomy Specimen.

An 89-year-old man with a history of percutaneous coronary intervention using a sirolimus-eluting stent presented with recurrent in-stent occlusion. Pathological assessment of the neointima resected via directional coronary atherectomy revealed a double-layered thrombus. Clopidogrel resistance and limited antithrombotic regimen owing to high bleeding risk likely resulted in the in-stent thrombotic occlusion.

Electromyography-controlled gamified exercise system for the distal upper extremity: a usability assessment in subacute post-stroke patients.

PURPOSE: Movement repetition is known to play a key role in promoting functional improvements or maintaining functional levels in post-stroke hemiparetic patients. However, repetitive movements tend to be monotonous, making it challenging for patients to continue. Here, we developed a new gamified system to allow patients perform repetitive movements with enjoyment. The present study aimed to examine the usability of the system in subacute stroke patients. METHOD: The exercise system comprised an electromyography-controlled operating system that enabled users to play a virtual game by repetitive finger and wrist movements on the affected side. A total of 13 patients with upper-limb hemiparesis underwent a single bout of exercise using the system and assessed its usability, satisfactoriness, enjoyability, etc. using the System Usability Scale (SUS), Quebec User Evaluation of Satisfaction with assistive Technology (QUEST)-like questionnaire, and numerical rating scale (NRS). RESULTS: All the participants, who had a wide range of paretic levels, were able to perform the exercise using the system. Participants scored the system a median of 85.0 for SUS and 4.2 for the QUEST-like questionnaire, with an "excellent" in usability and "satisfied" in user satisfaction with the system. The median NRS scores for enjoyability, potential for continuous use, and effectiveness were 8.0, 9.0, and 9.0, respectively, which were greater than the scores for usual rehabilitation training for the upper extremity. CONCLUSIONS: The novel electromyography-controlled gamified exercise system may have sufficient usability and enjoyability to motivate patients with a wide range of paretic levels to perform repetitive finger and wrist movements.IMPLICATIONS FOR REHABILITATIONThe electromyography-controlled gamified exercise system had overall positive perspectives on the usability of the system.This exercise system could help motivate patients with a wide range of paretic levels to perform repetitive finger and wrist movements.

Differences in prion strain conformations result from non-native interactions in a nucleus.

Aggregation-prone proteins often misfold into multiple distinct amyloid conformations that dictate different physiological impacts. Although amyloid formation is triggered by a transient nucleus, the mechanism by which an initial nucleus is formed and allows the protein to form a specific amyloid conformation has been unclear. Here we show that, before fiber formation, the prion domain (Sup35NM, consisting of residues 1-254) of yeast prion Sup35, the [PSI(+)] protein determinant, forms oligomers in a temperature-dependent, reversible manner. Mutational and biophysical analyses revealed that 'non-native' aromatic interactions outside the amyloid core drive oligomer formation by bringing together different Sup35NM monomers, which specifically leads to the formation of highly infectious strain conformations with more limited amyloid cores. Thus, transient non-native interactions in the initial nucleus are pivotal in determining the diversity of amyloid conformations and resulting prion strain phenotypes.

Distinct conformations of in vitro and in vivo amyloids of huntingtin-exon1 show different cytotoxicity.

A hallmark of polyglutamine diseases, including Huntington disease (HD), is the formation of beta-sheet-rich aggregates, called amyloid, of causative proteins with expanded polyglutamines. However, it has remained unclear whether the polyglutamine amyloid is a direct cause or simply a secondary manifestation of the pathology. Here we show that huntingtin-exon1 (thtt) with expanded polyglutamines remarkably misfolds into distinct amyloid conformations under different temperatures, such as 4 degrees C and 37 degrees C. The 4 degrees C amyloid has loop/turn structures together with mostly beta-sheets, including exposed polyglutamines, whereas the 37 degrees C amyloid has more extended and buried beta-sheets. By developing a method to efficiently introduce amyloid into mammalian cells, we found that the formation of the 4 degrees C amyloid led to substantial toxicity, whereas the toxic effects of the 37 degrees C amyloid were very small. Importantly, thtt amyloids in different brain regions of HD mice also had distinct conformations. The thermolabile thtt amyloid with loop/turn structures in the striatum showed higher toxicity, whereas the rigid thtt amyloid with more extended beta-sheets in the hippocampus and cerebellum had only mild toxic effects. These studies show that the thtt protein with expanded polyglutamines can misfold into distinct amyloid conformations and, depending on the conformations, the amyloids can be either toxic or nontoxic. Thus, the amyloid conformation of thtt may be a critical determinant of cytotoxicity in HD.

Effectiveness of Repetitive Facilitative Exercise Combined with Electrical Stimulation Therapy to Improve Very Severe Paretic Upper Limbs in with Stroke Patients: A Randomized Controlled Trial.

Background: The difference in the effects of combined therapy with repetitive facilitative exercise (RFE) and neuromuscular electrical stimulation (NMES) on stroke upper limb paralysis was only reported by a pilot study; it has not been investigated in many patients. Objective: We investigated the effect of combined therapy with RFE and NMES on stroke patients with severe upper paresis. Methods: This study included 99 of the very severe paresis stroke patients with scores of zero or 1a in the Finger-Function test of the Stroke Impairment Assessment Set (SIAS). We randomly divided the patients into four groups, namely, NMES, RFE, RFE under NMES, and conventional training (CT) groups. A total of 20 min of group-specific training in addition to 40 min of conventional exercise per day, seven times a week for 4 weeks after admission, was performed. The upper extremity items of the Fugl-Meyer Assessment (FMA) were evaluated before and after the training period. Results: The total score gains of the FMA, FMA wrist item, and FMA finger item were significantly larger in the RFE under NMES group than those in the CT group (p < 0.05). Conclusion: The combination of voluntary movement and electrical stimulation may promote the activation of paralyzed muscles and improve distal function for very severe paralyzed upper limbs.