Clarify Sit-to-Stand Muscle Synergy and Tension Changes in Subacute Stroke Rehabilitation by Musculoskeletal Modeling.

Post-stroke patients exhibit distinct muscle activation electromyography (EMG) features in sit-to-stand (STS) due to motor deficiency. Muscle activation amplitude, related to muscle tension and muscle synergy activation levels, is one of the defining EMG features that reflects post-stroke motor functioning and motor impairment. Although some qualitative findings are available, it is not clear if and how muscle activation amplitude-related biomechanical attributes may quantitatively reflect during subacute stroke rehabilitation. To better enable a longitudinal investigation into a patient's muscle activation changes during rehabilitation or an inter-subject comparison, EMG normalization is usually applied. However, current normalization methods using maximum voluntary contraction (MVC) or within-task peak/mean EMG may not be feasible when MVC cannot be obtained from stroke survivors due to motor paralysis and the subject of comparison is EMG amplitude. Here, focusing on the paretic side, we first propose a novel, joint torque-based normalization method that incorporates musculoskeletal modeling, forward dynamics simulation, and mathematical optimization. Next, upon method validation, we apply it to quantify changes in muscle tension and muscle synergy activation levels in STS motor control units for patients in subacute stroke rehabilitation. The novel method was validated against MVC-normalized EMG data from eight healthy participants, and it retained muscle activation amplitude differences for inter- and intra-subject comparisons. The proposed joint torque-based method was also compared with the common static optimization based on squared muscle activation and showed higher simulation accuracy overall. Serial STS measurements were conducted with four post-stroke patients during their subacute rehabilitation stay (137 ± 22 days) in the hospital. Quantitative results of patients suggest that maximum muscle tension and activation level of muscle synergy temporal patterns may reflect the effectiveness of subacute stroke rehabilitation. A quality comparison between muscle synergies computed with the conventional within-task peak/mean EMG normalization and our proposed method showed that the conventional was prone to activation amplitude overestimation and underestimation. The contributed method and findings help recapitulate and understand the post-stroke motor recovery process, which may facilitate developing more effective rehabilitation strategies for future stroke survivors.

Association between dyspeptic symptoms and endoscopic findings based on the Kyoto classification of gastritis in Japanese male.

The Kyoto gastritis classification is used to categorize the endoscopic characteristics of Helicobacter pylori infection-associated gastritis. We aimed to clarify the association among endoscopic findings and abdominal dyspeptic symptoms in Japanese male. We administered a questionnaire to 418 subjects who underwent endoscopy as part of a health check-up from August 2003 to April 2004 to investigate the association among endoscopic findings of the Kyoto classification and the presence of dyspeptic symptoms. Logistic regression analyses were performed to evaluate risk based on dyspeptic symptoms. Among 418 health check-up subjects, 21.3% (89/418) reported dyspeptic symptoms in the questionnaire. The incidence of fundic gland polyp among patients with dyspeptic symptoms was 12.4% (11/89), which was significantly higher than that among non-symptomatic subjects (4.3%, 14/329, p = 0.004). Logistic regression analyses showed that fundic gland polyp was a risk factor for dyspeptic symptoms [odds ratio (OR): 3.413, 95% confidence interval (CI): 1.430-8.142], while short-segment Barrett's esophagus and male sex were protective factors (OR: 0.569, 95% CI: 0.349-0.928 and OR: 0.333, 95% CI: 0.117-0.948, respectively). In conclusion, Endoscopic findings of fundic gland polyp may be associated with dyspeptic symptoms, which in turn may be a useful marker of gastric condition.

Classification of Motor Impairments of Post-Stroke Patients Based on Force Applied to a Handrail.

Many patients suffer from declined motor abilities after a brain injury. To provide appropriate rehabilitation programs and encourage motor-impaired patients to participate further in rehabilitation, sufficient and easy evaluation methodologies are necessary. This study is focused on the sit-to-stand motion of post-stroke patients because it is an important daily activity. Our previous study utilized muscle synergies (synchronized muscle activation) to classify the degree of motor impairment in patients and proposed appropriate rehabilitation methodologies. However, in our previous study, the patient was required to attach electromyography sensors to his/her body; thus, it was difficult to evaluate motor ability in daily circumstances. Here, we developed a handrail-type sensor that can measure the force applied to it. Using temporal features of the force data, the relationship between the degree of motor impairment and temporal features was clarified, and a classification model was developed using a random forest model to determine the degree of motor impairment in hemiplegic patients. The results show that hemiplegic patients with severe motor impairments tend to apply greater force to the handrail and use the handrail for a longer period. It was also determined that patients with severe motor impairments did not move forward while standing up, but relied more on the handrail to pull their upper body upward as compared to patients with moderate impairments. Furthermore, based on the developed classification model, patients were successfully classified as having severe or moderate impairments. The developed classification model can also detect long-term patient recovery. The handrail-type sensor does not require additional sensors on the patient's body and provides an easy evaluation methodology.

Synthesis and evaluation of in vivo anti-hypothermic effect of all stereoisomers of the thyrotropin-releasing hormone mimetic: Rovatirelin Hydrate.

We discovered the orally active thyrotropin-releasing hormone (TRH) mimetic: (4S,5S)-5-methyl-N-{(2S)-1-[(2R)-2-methylpyrrolidin-1-yl]-1-oxo-3-(1,3-thiazol-4-yl)propan-2-yl}-2-oxo-1,3-oxazolidine-4-carboxamide 1 (rovatirelin). The central nervous system (CNS) effect of rovatirelin after intravenous (iv) administration is 100-fold higher than that of TRH. As 1 has four asymmetric carbons in its molecule, there are 16 stereoisomers. We synthesized and evaluated the anti-hypothermic effect of all stereoisomers of 1, which has the (4S),(5S),(2S),(2R) configuration from the N-terminus to the C-terminus, in order to clarify the structure-activity relationship (SAR) of stereoisomers. The (4R),(5R),(2R),(2S)-isomer 16 did not show any anti-hypothermic effect. Only the (4S),(5S),(2S),(2S)-isomer 10, which has the (2S)-2-methylpyrrolidine moiety at the C-terminus showed the anti-hypothermic effect similar to 1. Stereoisomers, which have the (5R) configuration of the oxazolidinone at the N-terminus and the (2R) configuration at the middle-part, showed a much lower anti-hypothermic effect than that of 1. On the other hand, stereoisomers, which have the (4R) configuration of the oxazolidinone at the N-terminus or the (2S) configuration of the C-terminus, have little influence on the anti-hypothermic effect.

Temporal Features of Muscle Synergies in Sit-to-Stand Motion Reflect the Motor Impairment of Post-Stroke Patients.

Sit-to-stand (STS) motion is an important daily activity, and many post-stroke patients have difficulty performing STS motion. Previous studies found that there are four muscle synergies (synchronized muscle activations) in the STS motion of healthy adults. However, for post-stroke patients, it is unclear whether muscle synergies change and which features primarily reflect motor impairment. Here, we use a machine learning method to demonstrate that temporal features in two muscle synergies that contribute to hip rising and balance maintenance motion reflect the motor impairment of post-stroke patients. Analyzing the muscle synergies of age-matched healthy elderly people ( n = 12 ) and post-stroke patients ( n = 33 ), we found that the same four muscle synergies could account for the muscle activity of post-stroke patients. Also, we were able to distinguish post-stroke patients from healthy people on the basis of the temporal features of these muscle synergies. Furthermore, these temporal features were found to correlate with motor impairment of post-stroke patients. We conclude that post-stroke patients can still utilize the same number of muscle synergies as healthy people, but the temporal structure of muscle synergies changes as a result of motor impairment. This could lead to a new rehabilitation strategy for post-stroke patients that focuses on activation timing of muscle synergies.

Correction to Discovery of the Orally Effective Thyrotropin-Releasing Hormone Mimetic: 1-{N-[(4S,5S)-(5-Methyl-2-oxooxazolidine-4-yl)carbonyl]-3-(thiazol-4-yl)-l-alanyl}-(2R)-2-methylpyrrolidine Trihydrate (Rovatirelin Hydrate).

[This corrects the article DOI: 10.1021/acsomega.8b01481.].

Effects of the Number of Seeds per Berry on Fruit Growth Characteristics, Especially on the Duration of Stage II in Blueberry.

In present research, differences in the number of seeds per berry (NSB), berry fresh weight (BW), days to ripening from flowering (DRF), and the duration of a slow growth phase (DS II) among pollen sources were investigated in highbush blueberry (Vaccinium corymbosum). NSB, as well as BW and DRF, were significantly different among the pollen sources. Analysis of covariance (ANCOVA) with NSB as the covariate showed significant interaction between the NSB and pollen sources on BW and DRF when self-pollination was included. However, ANCOVA without self-pollination showed no significant effect of the pollen source on BW and DRF. On the other hand, DS II was negatively correlated with NSB, and no significant interaction between NSB and pollen sources was found, even though self-pollination was included. Although the relationship between NSB and DS II appeared not to be statistically influenced by the different pollen sources, there seemed to be some difference between self- and cross-pollination. DS II shortened as the NSB increased, which may have led to a decrease in DRF.

Discovery of the Orally Effective Thyrotropin-Releasing Hormone Mimetic: 1-{N-[(4S,5S)-(5-Methyl-2-oxooxazolidine-4-yl)carbonyl]-3-(thiazol-4-yl)-l-alanyl}-(2R)-2-methylpyrrolidine Trihydrate (Rovatirelin Hydrate).

We have explored orally effective thyrotropin-releasing hormone (TRH) mimetics, showing oral bioavailability and brain penetration by structure-activity relationship (SAR) study on the basis of in vivo antagonistic activity on reserpine-induced hypothermia in mice. By primary screening of the synthesized TRH mimetics, we found a novel TRH mimetic: l-pyroglutamyl-[3-(thiazol-4-yl)-l-alanyl]-l-prolinamide with a high central nervous system effect compared with TRH as a lead compound. Further SAR optimization studies of this lead compound led to discovery of a novel orally effective TRH mimetic: 1-{N-[(4S,5S)-(5-methyl-2-oxooxazolidine-4-yl)carbonyl]-3-(thiazol-4-yl)-l-alanyl}-(2R)-2-methylpyrrolidine trihydrate (rovatirelin hydrate), which was selected as a candidate for clinical trials.

A flow-through column electrolytic cell for supercritical fluid chromatography.

A novel flow-through column electrolytic cell was proposed as a detector to obtain current signals for supercritical fluid chromatography. The electrochemical cell consisted of two electrodes and its holder, and a working and a counter electrode were fabricated from 192 carbon strings, which were composed of 400 carbon fibers of 10 µm in diameter filled into a heat-shrinkable tube. These electrodes were placed in the center of a holder made from polyether ether ketone blocks and they were separated by polytetrafluoroethylene membrane filters. To evaluate the sensitivity of this cell, a standard solution of ferrocene was injected into the supercritical fluid chromatography system connected to the electrolytic cell. The ferrocene was eluted through a silica gel column using a mixture of a mobile phase of supercritical CO2 and a modifier of methanol containing ammonium acetate. The current peak area of ferrocene correlated to the ferrocene concentration in the range of 10-400 µmol/L (r = 0.999). Moreover, the limit of detection on the column estimated from a signal-to-noise ratio of 3 was 9.8  × 10-13  mol.

Novel treatment for early-stage nasal natural killer/T-cell lymphoma: intra-maxillary arterial infusion chemotherapy with concomitant radiotherapy.

Nasal natural killer (NK)/T-cell lymphoma (NNKTL) displays unusual clinicopathological features, and the prognosis is very poor, even in the early stages of the disease. For early stage NNKTL, we have developed a novel chemoradiotherapy regimen incorporating arterial infusion chemotherapy, administered via the superficial temporal artery, in combination with radiotherapy. The novel arterial infusion regimen consists of ifosfamide, carboplatin, methotrexate, peplomycin, and etoposide (MPVIC-P). From 2003 to 2011, 12 patients with early stage NNKTL were treated with the MPVIC-P regimen via arterial infusion with concomitant radiotherapy (54 Gy). We have previously reported on the presence of Epstein-Barr virus (EBV) genetic DNA in NNKTL. Therefore, the effect of the treatment was evaluated by using both clinical findings and serum EBV DNA copy number. The observation period ranged from 39 months to 111 months post-treatment (median: 81 months). All 12 patients achieved and maintained complete remission and, to date, show no sign of relapse. Serum EBV DNA copy numbers decreased to below detectable levels in all 12 patients tested. Manageable mucositis was the most common grade 3-4 toxicity, and it was seen in 10 (83%) patients. However, grade 3-4 hematological toxicity was only seen in 4 (33%) patients. We conclude that our regimen of intra-maxillary arterial chemotherapy with concomitant radiotherapy is an effective treatment with minimal toxicity for early stage NNKTL. Copyright © 2015 John Wiley & Sons, Ltd.

Full recovery case after 82 minutes out-of-hospital cardiac arrest: importance of chain of survival and predicting outcome.

A middle age man underwent immediate cardiopulmonary resuscitation (CPR) for ventricular fibrillation (VF) occurred in an ambulance. After arrival in a regional hospital, return of spontaneous circulation (ROSC) was achieved 82 minutes after the collapse. He was in coma even three hours after ROSC. So, he was transferred to our university hospital to receive therapeutic hypothermia (TH). An initial bispectral index (BIS) value suggested a favorable outcome. Thus we decided to aggressive therapies including TH of 34°C for 48 hours, followed by a very slow rewarming at the rate of 1°C per day. Eventually he was discharged from the hospital with good neurological state. This case shows us two points: 1) the importance of the chain of survival: CPR done immediately after the collapse, persistent CPR for refractory VF, followed by coronary interventions after ROSC, continuing care to the university hospital, 2) decision making for TH using BIS monitoring.

[A case of duplication of the transverse colon in adult, lined with ciliated columnar and squamous epithelium].

We report a rare case of duplication of the transverse colon in an adult. A 26-year-old male presented to our hospital with upper left abdominal pain and fever. An abdominal computed tomography scan revealed an inflammatory mass in the gastrocolic ligament. Although conservative management with fasting and antibiotics ameliorated the abdominal pain, the mass remained approximately 5cm at its largest diameter. Further investigation with a Gastrografin(®) enema revealed a fistula in the central part of the transverse colon. A perforation of the transverse colon was intraoperatively detected; therefore, both the intra-abdominal abscess and part of the transverse colon were excised. Pathological examination revealed duplication of the transverse colon that was lined with ciliated columnar epithelium, squamous epithelium, and heterotopic glands.

Development of an electric charge-tunable micro-column for capillary liquid chromatography.

An electric charge-tunable micro-column (CTMC) was developed as a precolumn for reversed-phase capillary chromatography using conductive carbon fibers as the stationary phase. The carbon fibers, which constitute one electrode, are packed into a heat-shrinkable tube, which is attached to a stainless-steel column body. The mobile phase flows into CTMC through a stainless-steel tube that acts as a counter electrode. The retention times for hydrophobic and ionic compounds are controlled by the applied potential. The characteristics, such as the electrolysis efficiency and shift in retention factor, were evaluated. As a case study, estrogens in spiked beef were analyzed by capillary chromatography. With no applied potential, the resolution between the unknown peak and estriol and the recoveries of estriol were 0.81 and 65.5%, respectively. These values improved to 1.2 and 78.8%, respectively, upon applying +500 mV. These results indicate that a high-resolution capillary chromatography system can be achieved with CTMC.

Crystal structure, spin polarization, solid-state electrochemistry, and high n-type carrier mobility of a paramagnetic semiconductor: vanadyl tetrakis(thiadiazole)porphyrazine.

We report the synthesis, crystal structure, and magnetic, electrochemical, and carrier-transport properties of vanadyl tetrakis(thiadiazole)porphyrazine (abbreviated as VOTTDPz) with S = ½. X-ray crystal analysis reveals two polymorphs, the α and ß forms; the former consists of a 1D regular π stacking, while the latter forms a 2D π network. Molecular orbital calculations suggest a V(4+)(d(1)) ground state and a characteristic spin polarization on the whole molecular skeleton. The temperature dependence of the paramagnetic susceptibility of the α form clearly indicates a ferromagnetic interaction with a positive Weiss constant of θ = 2.4 K, which is well-explained by McConnell's type I mechanism. VOTTDPz forms amorphous thin films with a flat and smooth surface, and their cyclic voltammogram curves indicate a one-electron reduction process, which is highly electrochromic, because of a reduction of the porphyrazine π ring. Thin-film field-effect transistors of VOTTDPz with ionic-liquid gate dielectrics exhibit n-type performance, with a high mobility of µ = 2.8 × 10(-2) cm(2) V(-1) s(-1) and an on/off ratio of 10(4), even though the thin films are amorphous.

IL-1beta in the trigeminal subnucleus caudalis contributes to extra-territorial allodynia/hyperalgesia following a trigeminal nerve injury.

It has been reported that the whisker pad (WP) area, which is innervated by the second branch of the trigeminal nerve, shows allodynia/hyperalgesia following transection of the mental nerve (MN: the third branch of the trigeminal nerve). However, the mechanisms of this extra-territorial pain induction still remain unclear. Glia and cytokines are known to facilitate perception of noxious input, raising a possibility that these non-neuronal elements are involved in the induction and spread of allodynia/hyperalgesia at non-injured skin territory. One day after MN transection, tactile allodynia/hyperalgesia developed on the ipsilateral WP area, which is in the non-injured skin territory. The tactile allodynia/hyperalgesia lasted for more than 56 days. In response to MN transection, astrocytes and microglia appeared to be in an activated state, and interleukin (IL)-1beta was up-regulated in astrocytes in the trigeminal subnucleus caudalis (Vc). Allodynia/hyperalgesia at WP area induced by MN transection was attenuated dose-dependently by IL-1 receptor antagonist IL-1ra (i.t., 0.05, 0.5, and 5 pg/rat). Fos-like immunoreactive (Fos-Li) neurons were observed in the Vc after non-noxious mechanical stimulation of the WP area in the rats with MN transection. Administration of IL-1ra also attenuated the number of Fos-Li neurons dose-dependently. Administration of a noncompetitive antagonist of NMDA receptors MK-801 (i.t., 5 µg/rat) reversed allodynia/hyperalgesia. IL-1 receptor type I (IL-1RI) was localized in Fos- and phospho NR1-immunoreactive neurons. These results suggest that IL-1beta in the Vc plays an important role in the development of extra-territorial tactile allodynia/hyperalgesia after MN transection.

Column switching high-performance liquid chromatography with two channels electrochemical detection for high-sensitive determination of isoflavones.

Column switching HPLC with electrochemical detection (HPLC-ED), which consists of one pre-column and two electrochemical detectors subsequent to each analytical column, called HPLC-2ED, has been developed for determining isoflavones (daidzin, genistin, daidzein, and genistein) with high sensitivity. In the present HPLC-2ED, the eluted daidzin and genistin from the pre-column were separated on an analytical column using a methanol-water-phosphoric acid mixture (30:70:0.5) as the mobile phase (MP), and daidzein and genistein were separated on another analytical column using a methanol-water-phosphoric acid mixture (50:50:0.5). The way of the elute flow from the pre-column was changed by rotating the switching valve at 17 min. The difference in retention times of genistein between isocratic HPLC-ED and HPLC-2ED was 52.2 min. The detection limit (S/N=3) per column injection (5 microL) of genistein was 0.5 pg. The sensitivity by the present method is superior to that of previously reported gradient HPLC-ED for the determination of isoflavones.

Role of Na+/L-carnitine transporter (OCTN2) in renal handling of pivaloylcarnitine and valproylcarnitine formed during pivalic acid-containing prodrugs and valproic acid treatment.

Pivalic acid and valproic acid decreases L-carnitine concentration in the body via urinary excretion of their acylcarnitines, pivaloylcarnitine (PC) and valproylcarnitine (VC). To obtain an information about the mechanism of the physiological response, we investigated the renal handling of these acylcarnitines by Na+/L-carnitine cotransporter, OCTN2 using the isolated perfused rat kidney, rat OCTN2 (rOCTN2) and human OCTN2 (hOCTN2) expressing cells. In the perfused rat kidney, PC and VC were strongly reabsorbed with an efficiency comparable to L-carnitine, and these reabsorption were inhibited by 1 mM L-carnitine, suggesting that the interaction of L-carnitine with PC and VC reabsorption would be responsible for renal handling of these acylcarnitines in rats. The rOCTN2-mediated uptake of PC was lower than that of L-carnitine, whereas rOCTN2-mediated uptake of VC was as high as that of L-carnitine, indicating that contribution of rOCTN2 in renal handling of PC and VC would be different. Furthermore, hOCTN2-mediated uptake of these acylcarnitines was markedly lower than that of L-carnitine. On the other hand, both PC and VC inhibited L-carnitine reabsorption in the perfused rat kidney and their concentration-dependent inhibition was also observed for rOCTN2 and hOCTN2. These results suggest that low renal reabsorption and interaction of hOCTN2 for these acylcarnitines might possibly affect the decrease of L-carnitine concentration in humans.

[A case of toxic epidermal necrolysis with severe intestinal manifestation].

TEN is a severe dermatological disorder characterized by extended epidermal necrosis. Disseminated mucosal erosions have been occasionally reported to occur in the gastrointestinal tract. We report a case of toxic epidermal necrolysis (TEN) with severe intestinal manifestation. A 52-year-old woman was admitted with high fever, skin eruption and severe diarrhea. She was diagnosed as toxic epidermal necrolysis (TEN), which was most likely due to nonsteroidal anti-inflammatory drugs (NSAIDs). After skin lesion recovered, fever and bloody diarrhea went on. Colonoscopy and X-ray revealed lead-pipe like stenotic long loops which was caused by erosion and sublation of whole mucosa of large intestinum, and severe stenosis of ileum end. The ileo-cecal region was resected on the 216(th) hospital day. Pathological examination showed sublation of mucoepithelium and inflammatory change in the muco-submucosal layer, but muscular layers of mucosa remained intact. Pathologically, the intestinal lesion resemble the changes in the early skin lesions and seems to be part of the systemic lesion of TEN.

Attomole catechins determination by capillary liquid chromatography with electrochemical detection.

Attomole quantities of catechins were determined by a capillary liquid chromatography system with electrochemical detection (CLC-ECD) and the system is applied to the determination of catechins in human plasma. The eight catechins: catechin (C), epicatechin (EC), gallocatechin (GC), epigallocatechin (EGC), catechin gallate (Cg), epicatechin gallate (ECg), gallocatechin gallate (GCg), and epigallocatechin gallate (EGCg), were separated within 10 min using a capillary column (0.2 mm i.d.) and a mobile phase of phosphoric acid (85%)-methanol-water (0.5:27.5:72.5, v/v/v), and were detected at +0.85 V vs. Ag/AgCl. Peak heights were found to be linearly related to the amount of catechins injected, from 200 amol to 500 fmol (r > 0.998). The detection limits of the catechins were 61 amol for EGC, 75 amol for EC, 54 amol for GC, 61 amol for C, 67 amol for GCg, 75 amol for EGCg, 75 amol for ECg and 89 amol for Cg (S/N = 3). Because the present method is highly sensitive and allows facile pretreatment for plasma sample, the time courses of concentrations of catechins (GCg, EC, EGCg, ECg, and Cg) and their conjugates in human plasma obtained from a 10 microl plasma sample after ingestion of green tea could be determined.

The use of enamel matrix derivative (Emdogain) for improvement of probing attachment level of the autotransplanted teeth.

The enamel matrix derivative (EMD, Emdogain) was used for the purpose to obtain the periodontal regeneration on the denuded root-surfaces of the donor teeth in two cases of the immediate tooth-transplantation. The root-surfaces at the cervical portion of the teeth were denuded because of extrusion. The healthy periodontium of each tooth remained at the apical portion of the roots. The denuded root-surfaces were cleansed before extraction. Then, the donor teeth were gently extracted with forceps, administered EMD, and transplanted so that the denuded surfaces were covered by gingival flaps. After the transplantation, the mean probing attachment level (PAL) improved 3.2 mm and 1.5 mm, respectively. The mean probing pocket depth was within normal level. The actual supporting areas of the roots of the transplanted teeth increased and the teeth worked as the abutments of prosthetic bridges.