Quality Management Program of Stroke Rehabilitation Using Adherence to Guidelines: A Nationwide Initiative in Japan.

BACKGROUND AND AIM: In recent years, interest in the quality of medical care has rapidly increased worldwide. However, quality indicators that contribute to establishing standard treatment in stroke medicine, especially rehabilitation, are not well-developed in Japan. Japan has established Kaifukuki (convalescent) rehabilitation wards, and the development of quality indicators for stroke rehabilitation in the convalescent phase is an urgent issue. METHODS: We first reviewed the literature regarding quality indicators for stroke rehabilitation. Next, we extracted candidate indicators from identified reports and guidelines and surveyed educational hospitals certified by the Japanese Association of Rehabilitation Medicine. On the basis of the survey results, we reevaluated the suitability of the proposed indicators in discussions with an expert panel. RESULTS: The questionnaire survey highlighted several important items that revealed there is room for improvement in adherence. For stroke rehabilitation in the convalescent phase, we adopted 15 indicators that were feasible as indicators to be used for comparisons between facilities, based on scoring by and opinions of the expert panel. These indicators measured structure (2 indicators), process (5 indicators), and outcome (8 indicators). CONCLUSION: This is the first study to establish quality indicators to standardize stroke rehabilitation in Japan. We developed this set of 15 indicators using an evidence-based approach. However, many tasks remain for continuous quality improvement.

Intra-rater and inter-rater reliability of the portable gait rhythmogram in post-stroke patients.

[Purpose] Gait analysis, such as portable gait rhythmogram (PGR) provides objective information that helps in the quantitative evaluation of human locomotion. The purpose of this study was to assess the reliability of PGR in post-stroke patients. [Subjects and Methods] Two raters (A and B) examined 44 post-stroke patients. To assess intra-rater reliability, rater A tested subjects on three separate occasions (Days 1, 2, and 3). To assess inter-rater reliability, raters A and B independently tested participants on the same occasion (Day 3). [Results] There was no significant systematic bias between test occasions or raters. Intraclass correlation coefficient values were 0.93-0.97 for intra-rater reliability at both the comfortable speed and maximum speed, and 0.97-0.98 (comfortable speed) and 0.87-0.99 (maximum speed) for inter-rater reliability. The standard error was 1.25-1.49 (comfortable speed) and 1.62-1.77 (maximum speed) for intra-rater investigation, and 1.04-1.32 (comfortable speed) and 0.91-1.26 (maximum speed) for inter-rater investigation. At the 90% confidence level, the minimum detectable change ranged from 2.9-4.1%, and the error of an individual's score at a given time point ranged from ±2.1-2.9%. [Conclusion] Based on this excellent reliability of the PGR in post-stroke patients, it can be recommended as a simple test of gait analysis in this population.

Pre-existing Mobile Cardiac Thrombus and the Risk of Early Recurrent Embolism after Intravenous Thrombolysis: A Case Report.

BACKGROUND: Early recurrence of an embolism is rarely observed in patients with stroke treated with intravenous thrombolysis. Pre-existing cardiac thrombus is thought as a risk factor for recurrent embolism, although the relationship remains unclear. METHODS: The present patient was a 30-year-old man with acute ischemic stroke. Transthoracic echocardiography performed before thrombolysis demonstrated an intraventricular mobile thrombus, and the patient was treated with intravenous thrombolysis 183 minutes after the onset of stroke. During thrombolysis, he suffered from a peripheral artery embolism, without further signs of neurologic deterioration. Repeated transthoracic echocardiography showed the disappearance of the intraventricular thrombus. However, follow-up magnetic resonance imaging disclosed new ischemic lesions at the splenium of the corpus callosum, and body computed tomography showed infarction of the spleen and kidney. The peripheral artery embolism improved spontaneously without further evidence of recurrent embolism. RESULTS: This is the first report to provide findings of an intracardiac mobile thrombus before thrombolysis and to demonstrate the acceleration of detachment of the thrombus during thrombolysis. CONCLUSIONS: Because there are currently no guidelines for the use of intravenous thrombolysis for acute ischemic stroke associated with a pre-existing intracardiac thrombus with respect to the efficacy and safety, physicians should pay special attention to similar cases.

Structure consideration of platinum nanoparticles constructing nanostructures obtained by electrochemical dealloying of a Cu-Pt alloy.

Many nanoporous metals have been applied for catalysis and show active properties. In this study, nanoporous platinum was successfully prepared from a Cu-Pt (50/50 w/w) alloy plate by electrochemical dealloying. In order to reveal their detailed structures in nanometer order, TEM observation of the surface area of the alloy plate was performed by using focused ion beam (FIB) for sample preparation. Peeling off the surface platinum nanoparticles could be also successfully preformed by using ultra sonification and their TEM observation revealed the units of the platinum nanoporous structures.

Disorders of Consciousness after Subacute Stroke Might Partly be Caused by Carnitine Deficiency: Two Case Reports.

Background: Carnitine is a vital human nutrient. Although there are many reports on carnitine deficiency, most studies have been conducted on children, patients with severe mental and physical disabilities, epileptic patients, patients with liver cirrhosis, and dialysis patients. To the best of our knowledge, there are no reports on carnitine administration for disorders of consciousness after stroke. We report two such cases in which carnitine administration improved disorders of consciousness. Cases: Case 1 was a woman in her sixties who was admitted to our rehabilitation center 4 months after the onset of subarachnoid hemorrhage. After admission, her disorders of consciousness worsened even though she was actively undergoing rehabilitation. Suspecting carnitine deficiency, we administered 1500 mg/day of L-carnitine, which resulted in improvement of her disorders of consciousness and disappearance of symptoms such as convulsions. Case 2 was a man in his thirties who was admitted to our rehabilitation center 5 months after the onset of cerebral hemorrhage. During active rehabilitation, he suffered worsening disorders of consciousness, convulsions, and cramps. We found carnitine deficiency with a blood carnitine concentration of 21 mg/dL, so we administered 1500 mg/day of L-carnitine; symptoms of disorders of consciousness and convulsions then improved. Discussion: It is possible that carnitine deficiency has been overlooked in some patients in rehabilitation wards, and measurement of ammonia might facilitate its detection. Because carnitine deficiency can interfere with active rehabilitation, nutritional management with attention to carnitine deficiency could be important during rehabilitation.

Microstructure and Strength of Ti-6Al-4V Samples Additively Manufactured with TiC Heterogeneous Nucleation Site Particles.

Our research aims to investigate the fabrication of additively manufactured (AMed) Ti-6Al-4V samples under reduced power with the addition of TiC heterogeneous nucleation site particles. For this aim, Ti-6Al-4V samples are fabricated with and without TiC heterogeneous nucleation site particles using an EOS M 290 machine under optimal parameters and reduced power conditions. The microstructure and tensile behavior of the produced samples were studied. In addition, a single-track test was performed to obtain a good understanding of the suppression of gas pores and balling formation with the addition of TiC heterogeneous nucleation site particles. It was found that the formation of gas pores and balling was suppressed with the addition of heterogeneous nucleation site particles within the metallic powder.

Four-year treatment continuation rates of osteoporosis drugs with different dosing intervals throughout Japan.

INTRODUCTION: There are approximately 13 million patients with osteoporosis in Japan; however, only 20% of them receive treatment. This study compared the 4-year continuation rates of osteoporosis drugs at different dosing intervals across throughout Japan. MATERIALS AND METHODS: Receipt data were analyzed to determine the continuation of osteoporosis medication in patients who began treatment at 210 hospitals throughout Japan between October 2016 and September 2017. Continuation rates were compared using Kaplan-Meier curves and log-rank tests. RESULTS: The 4-year continuation rates of daily, weekly, monthly, semi-annual, and yearly medications nationwide were 8.6%, 16.5%, 13.5%, 31.0%, and 26.0%, respectively. The 4-year continuation rates for semi-annual and yearly drugs were significantly higher than daily, weekly, monthly drugs. CONCLUSION: Throughout Japan, the 4-year treatment continuation rates of daily, weekly, monthly, semi-annual, and yearly osteoporosis drugs all decreased over time. However, the continuation rates of semi-annual and yearly drugs in the fourth year were significantly higher than those for the other dosing regimens. Therefore, injectable drugs with dosing intervals ≥6 months may improve continuation rates of osteoporosis drugs. Geriatr Gerontol Int 2023; 23: 665-670.

Reliability of the portable gait rhythmogram in post-stroke patients.

BACKGROUND: Gait analysis, such as portable gait rhythmogram (PGR), provides objective information that helps in the quantitative evaluation of human locomotion. OBJECTIVE: The purpose of this study was to assess the reliability of PGR in post-stroke patients. METHODS: Two raters (A and B) examined 48 post-stroke patients. To assess intra-rater reliability, rater A tested subjects on three separate occasions (Days 1, 2, and 3). To assess inter-rater reliability, raters A and B independently tested participants on the same occasion (Day 3). RESULTS: There was no significant systematic bias between test occasions or raters. Intraclass correlation coefficient values were 0.93-0.97 for intra-rater reliability at both the comfortable speed and maximum speed, and 0.97-0.98 (comfortable speed) and 0.97-0.99 (maximum speed) for inter-rater reliability. The standard error was 1.25-1.49 (comfortable speed) and 1.62-1.77 (maximum speed) for intra-rater investigation, and 1.04-1.32 (comfortable speed) and 0.91-1.26 (maximum speed) for inter-rater investigation. At the 90% confidence level, the minimum detectable change ranged from 2.9-4.1%, and the error of an individual's score at a given time point ranged from ±2.1-2.9%. CONCLUSIONS: Based on this excellent reliability of the PGR in post-stroke patients, it can be recommended as a simple test of gait analysis in this population.

Effects of concomitant neuromuscular electrical stimulation during repetitive transcranial magnetic stimulation before repetitive facilitation exercise on the hemiparetic hand.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) and Repetitive facilitative exercise (RFE) improves motor impairment after stroke. OBJECTIVE: To investigate whether neuromuscular electrical stimulation (NMES) can facilitate the effects of rTMS and RFE on the function of the hemiparetic hand in stroke patients. METHODS: This randomized double-blinded crossover study divided 20 patients with hemiparesis into two groups and provided treatment for 4 weeks at 5 days/week. NMES-before-sham group and NMES-following-sham group performed NMES sessions and sham NMES sessions for each 2 weeks. Patients received NMES or sham NMES for the affected extensor muscle concurrently with 1 Hz rTMS for the unaffected motor cortex for 10 min and performed RFE for 60 min. The Fugl-Meyer Assessment (FMA), Action Research Arm Test (ARAT), Box and Block Test (BBT) and Modified Ashworth Scale (MAS) were used for evaluation. RESULTS: FMA and ARAT improved significantly during both sessions. The gains in the BBT during an NMES session were significantly greater than those during a sham NMES session. MAS for the wrist and finger significantly decreased only during an NMES session. CONCLUSIONS: NMES combined with rTMS might facilitate, at least in part, the beneficial effects of RFE on motor function and spasticity of the affected upper limb.

Transdermal delivery of 40-nm silk fibroin nanoparticles.

Transdermal administration of drugs improves their bioavailability and is capable of systemic and local treatment. To improve the skin permeability of drugs, nano-sized systems have attracted attention as drug carriers for transdermal drug delivery system. We considered that silk fibroin composed of a crystalline region with many hydrophobic amino acids and an amorphous region with many hydrophilic amino acids was useful as a carrier for transdermal administration of a drug because of the balance between hydrophilicity and hydrophobicity. In this study, silk fibroin nanoparticles with mean volume diameters of 42.3 nm were successfully prepared, and storage stability was confirmed by storing the nanoparticle suspension at 4, 32, and 37 °C for a week. At any storage temperature, the mean volume diameter and standard deviation were stable. The polydispersity indexes were 0.19-0.23, and no specific trends were observed. Then, to investigate the transdermal delivery route of the silk fibroin nanoparticles, skin permeability in vivo was evaluated using mice. Six hours after administration, fluorescent substances were observed in the dermis in addition to the stratum corneum, hair follicles and the epidermis around them. This result indicated that fibroin nanoparticles with the mean volume diameter of 40-nm penetrated the stratum corneum and was delivered deep into the skin. Therefore, it was suggested that small nanoparticles prepared using silk fibroin are useful for drug delivery to the dermis.

Development of fructosyl amine oxidase specific to fructosyl valine by site-directed mutagenesis.

Docking models of fructosyl amine oxidase (FAOD) from the marine yeast Pichia N1-1 (N1-1 FAOD) with the substrates fructosyl valine (f-Val) and fructosyl-(epsilon)N-lysine (f-(epsilon)Lys) were produced using three-dimensional protein model as reported previously (Miura et al., 2006, Biotechnol. Lett., 28, 1895-1900). The residues involved in recognition of substrates were proposed, particularly Asn354, which interacts closely with f-(epsilon)Lys, but not with f-Val. Substitution of Asn354 to histidine and lysine simultaneously resulted in an increase in activity of f-val and a decrease in activity of f-(epsilon)Lys and thus, increasing the specificity for f-Val from 13- to 19-fold. In addition to creating two mutant FAODs with great potential for the measurement of glycated hemoglobin, we have provided the first structural model of substrate binding with eukaryotic FAOD, which is expected to contribute to further investigation of FAOD.

Mirror therapy for involuntary movement due to chronic thalamic hemorrhage: a case report.

BACKGROUND: Some stroke survivors suffer from involuntary movement, which often disturbs upper-limb function, but there are few effective modality options. CASE REPORT: A 70-year-old man presented with persisting right-upper-limb hemiballism due to left thalamic hemorrhage ten years before. We provided inpatient rehabilitation, including repetitive-facilitative exercise and task-related training, and prescribed clonazepam from day 5 after admission. However, the affected upper limb showed no significant change and remained nonfunctional. When we introduced mirror therapy (MT) to the rehabilitation program on day 14, hemiballism immediately decreased during the MT session, so we added daily MT sessions of 20 min/day. At discharge on day 42, he was able to use his right hand for eating meals and folding laundry. CLINICAL REHABILITATION IMPACT: This shows that MT may have the potential to be a novel therapeutic method for treating involuntary movement. Further research is needed to elucidate mechanisms by which MT may reduce hemiballism.

A proposal of clinical ECG index "vagal score" for determining the mechanism of paroxysmal atrioventricular block.

BACKGROUND: Paroxysmal atrioventricular block (P-AVB) is a well-known cause of syncope; however, its underlying mechanism is difficult to determine. This study aimed to evaluate a new ECG index, the "vagal score (VS)," to determine the mechanism of P-AVB. METHODS: We evaluated the VS in 20 patients with P-AVB (13 men, 7 women; aged 25-78 years [mean, 59.3 years]). The VS was developed by assigning 1 point each for the following: (1) no AVB or intraventricular conduction disturbance on the baseline ECG, (2) PR prolongation immediately before P-AVB, (3) sinus slowing immediately before P-AVB, (4) initiation of P-AVB by PP prolongation, (5) sinus slowing during ventricular asystole, and (6) resumption of AV conduction with PP shortening, and by assigning -1 point each for (7) the initiation of P-AVB by a premature beat, and (8) resumption of AV conduction by an escape beat. Based on the clinical situations and electrophysiologic findings, we considered the mechanism of P-AVB as vagally mediated or intrinsic conduction disease (ICD). RESULTS: The VS ranged from 5 to -2 points for each patient. Five patients with a definite vagally mediated P-AVB had high VSs (3-5 points). We observed characteristic ECG findings of ICD consisting of changes in AV conduction by an extrasystole and/or escape beat in only 5 of the 6 patients (83%) with a low VS (1 to -2). CONCLUSIONS: The VS is simple and potentially useful for determining the mechanism of P-AVB. P-AVB with a VS ≥3 strongly suggested a vagally mediated mechanism.

Left Atrial Appendage Volume and Plasma Docosahexaenoic Acid Levels Are Associated With Atrial Fibrillation Recurrence After Catheter Ablation.

BACKGROUND: Risk factors for atrial fibrillation (AF) recurrence in patients who have undergone AF catheter ablation have not been fully clarified. The objective of this study was to assess whether the left atrium (LA) and LA appendage (LAA) volumes, and cardio-metabolic markers such as polyunsaturated fatty acids (PUFAs) levels were associated with AF recurrence. METHODS: Seventy-seven consecutive patients with AF (mean age, 59 ± 8 years; male, 81%; paroxysmal AF, 64%) undergoing catheter ablation were enrolled. Using contrast-enhanced cardiac multi-detector computed tomography (MDCT) scan, the LA and LAA volume and orifice area were assessed. Radiofrequency ablation was performed by an irrigation catheter, initially targeting the pulmonary veins with a wide area circumferential ablation. RESULTS: Patients with AF recurrence (36%) exhibited both larger LAA volumes and an LAA orifice area than those without AF recurrence, whereas the LA diameter and LA volumes were not significantly different. Notably, AF recurrence occurred in all patients with a large LAA (≥ 25 mL), and the LAA volume was significantly and negatively associated with docosahexaenoic acid (DHA) levels (ß = -0.33, P = 0.003). A multiple regression analysis revealed that the log N-terminal proB-type natriuretic peptide and plasma DHA levels were independent factors for the LAA volume when adjusted for age, AF detected age, left ventricular (LV) ejection fraction, end-systolic LV diameter. CONCLUSIONS: These results suggest that the association between LAA volume and low plasma DHA levels may be an important factor for post-ablation AF recurrence.

Active site analysis of fructosyl amine oxidase using homology modeling and site-directed mutagenesis.

A three-dimensional structural model of fructosyl amine oxidase from the marine yeast Pichia N1-1 was generated using the crystal structure of monomeric sarcosine oxidase from Bacillus sp. B-0618 as template. The putative active site region was investigated by site-directed mutagenesis, identifying several amino acid residues likely playing important roles in the enzyme reaction. Asn354 was identified as a residue that plays an important role in substrate recognition and that can be substituted in order to change substrate specificity while maintaining high catalytic activity. While the Asn354Ala substitution had no effect on the V (max) K (m) (-1) value for fructosyl valine, the V (max) K (m) (-1) value for fructosyl-(epsilon) N-lysine was decreased 3-fold, thus resulting in a 3-fold improvement in specificity for fructosyl valine over fructosyl-(epsilon) N-lysine.

An adult case of polysplenia syndrome associated with sinus node dysfunction, dextrocardia, and systemic venous anomalies.

A 54-year-old woman was referred to our hospital for symptomatic sinus bradyarrhythmia with a sinus pause of 8 seconds. She was diagnosed with dextrocardia during childhood and discovered to have heterotaxy syndrome when she had an appendectomy during her teenager years. Chest and abdominal examinations by computed tomography showed multiple spleens located on the right side and abnormal drainages of the superior and inferior vena cava. Left isomerism was diagnosed by bilaterally bilobed lungs. Because of a patent bilateral superior vena cava, pacemaker leads were implanted using the right cephalic vein approach. Her fainting symptoms disappeared after pacemaker implantation.

Successful treatment of nocturnal eating/drinking syndrome with selective serotonin reuptake inhibitors.

Nocturnal eating/drinking disorder (NE/DS) is a rare syndrome that includes disorders of both eating and sleeping. It is characterized by awakening in the middle of the night, getting out of bed, and consuming large quantities of food quickly and uncontrollably, then returning to sleep. This may occur several times during the night. Some patients are fully conscious during their nocturnal eating, while some report total amnesia. The aetiology of NE/DS is still unclear, and there is no satisfactory treatment. Four patients with NE/DS are described. Treatment with a selective seroronin reuptake inhibitor (SSRI) was effective in controlling their episodes of nocturnal eating. To our knowledge, this is the first published case report of successful treatment with SSRIs in NE/DS.

Cloning and expression of fructosyl-amine oxidase from marine yeast Pichia species N1-1.

The gene encoding the fructosyl-amine oxidase (FAOD) from the marine yeast Pichia sp. N1-1 was cloned and expressed in Escherichia coli. Partial amino acid sequence analysis of the Pichia sp. N1-1 FAOD allowed the design of oligonucleotide primers for the amplification of the gene by inverse polymerase chain reaction. The FAOD gene was found to be devoid of introns and to encode a 48-kDa protein composed of 429 amino acid residues. The FAD-binding consensus sequence GXGXXG: and the FAD covalent attachment-site cysteine residue have been identified within the predicted amino acid sequence. Comparisons with the amino acid sequences of other eukaryotic FAODs showed only 30% to 40% identities, establishing that the isolated Pichia N1-1 gene encodes a unique FAOD. Recombinant FAOD expression levels in E. coli reached 0.48 U/mg of soluble protein, which is considerably greater than native expression levels by inducing Pichia sp. N1-1 with fructosyl-valine (f-Val). The kinetic properties of the recombinant enzyme were almost indistinguishable from those of the native enzyme. We previously reported on the construction of a number of effective Pichia sp. N1-1 FAOD-based biosensors for measuring f-Val, a model compound for glycated hemoglobin. The further development of these biosensor systems can now greatly benefit from protein engineering and recombinant expression of the FAOD from Pichia N1-1.

A Multilayered Cell Culture Model for Transport Study in Solid Tumors: Evaluation of Tissue Penetration of Polyethyleneimine Based Cationic Micelles.

Limited drug distribution is partially responsible for the efficacy gap between preclinical and clinical studies of nano-sized drug carriers for cancer therapy. In this study, we examined the transport behavior of cationic micelles formed from a triblock copolymer of poly(D,L-lactide-co-glycolide)-block-branched polyethyleneimine-block-poly(D,L-lactide-co-glycolide) using a unique in vitro tumor model composed of a multilayered cell culture (MCC) and an Ussing chamber system. The Cy3-labeled cationic micelles showed remarkable Cy3 distribution in the MCC whereas charge-shielded micelles with a poly(ethylene glycol) surface accumulated on the surface of the MCC. Penetration occurred against convectional flow caused by a hydraulic pressure gradient. The study using fluorescence resonance energy transfer (FRET) showed that the cationic micelles dissociate at the interface between the culture media and the MCC or possibly inside of the first-layer cells and penetrates into the MCC as unimers. The penetration and distribution were energy-dependent and suppressed by various endocytic inhibitors. These suggest that cationic unimers mainly utilized clathrin-mediated endocytosis and macropinocytosis for cellular entry and a significant fraction were exocytosed by an unknown mechanism.

pH-responsive and charge shielded cationic micelle of poly(L-histidine)-block-short branched PEI for acidic cancer treatment.

To address cancer cell heterogeneity while endowing tumor specificity, the approach of charge shielding/deshielding was tested in vitro and in vivo with a paclitaxel loaded cationic micelle from a block copolymer of poly(L-histidine) (3.7kDa) and short branched polyethyleneimine (1.8 kDa). The cationic micelle surface was shielded by electrostatically complexing with a negatively charged mPEG (2 kDa)-block-polysulfadimethoxine (4 kDa) (mPEG-b-PSDM) at pH7.4. Unshielded micelle at pH7.4 and deshielded micelle at tumor extracellular pH were readily taken up by two wild types of human cancer cell lines, MCF-7 breast adenocarcinoma and SKOV-3 ovarian carcinoma, while the uptake of the shielded micelle at pH7.4 was minimal. The preliminary in vivo results from a mouse model xenografted with MCF-7 showed significant anticancer therapeutic efficacy and deep penetration of the micelle into tumor tissues after deshielding, supporting the unique pH-responsive mechanism to treat acidic cancer.