Leveraging an advanced simulated moving bed approach to achieve 3-component separation for enhanced impurity removal in a non-affinity cation exchange capture step.

One of the key challenges in downstream bioprocessing is to obtain products of high purity in a productive fashion through the effective removal of process and product related impurities. While a classical simulated moving bed (SMB) system operation can typically achieve a 2-component separation between the weakly bound impurities and target species, here we present an advanced SMB approach that can achieve a 3-component separation, including the removal of the strongly bound impurities from the target species. As a proof-of-concept, we demonstrate the enhanced removal of strongly bound host cell proteins (HCP) from the target monoclonal antibody (mAb) through the utilisation of the advanced SMB approach in a non-affinity cation exchange (CEX) capture step. In this way, 1 less polishing step was required to achieve the therapeutic requirements of < 100 ppm HCP and the overall process recovery was increased by ~ 6% compared to the corresponding process that utilised a batch CEX operation. The non-affinity CEX capture platform technology established through the utilisation of the advanced SMB approach presented here can potentially be further applied to address the downstream processing challenges presented by other challenging biotherapeutic modalities to yield a final target product with improved purity and recovery.

[Sports-Related Concussion:Update beyond the Japanese Guidelines for the Treatment and Management of Head Trauma].

All the statements regarding sports-related concussion(SRC)in our guidelines are generally simple but somewhat unfavorable. SRC is diagnosed solely by symptoms, without any definitive diagnostic measures. Various pathophysiologies are suspected to underlie SRC, making single diagnostic biomarker or neuroimaging unreliable. It is widely acknowledged that casualties of SRC should return to play gradually in a stepwise fashion; however, effective treatment and rehabilitation need to be determined. Although the pathological findings of chronic traumatic encephalopathy(CTE), possibly the result of repetitive injuries, have been elucidated, further research is needed to establish a clinical diagnosis and testing modalities for CTE.

Biomechanical Analysis of Serious Neck Injuries Resulting from Judo.

To establish a basis for initial diagnosis and for proposing preventive measures for the serious neck injuries occasionally experienced by judo practitioners, the biomechanical mechanisms of these injuries were analyzed. Two male judo experts repeatedly threw an anthropomorphic test device (POLAR dummy) using three throwing techniques (Seoi-nage, Osoto-gari, and Ouchi-gari). The dummy's kinematic data were captured using a high-speed digital camera, and the load and moment of the neck were measured with load cells. The neck injury criterion (Nij) and beam criterion were also calculated. In Seoi-nage, the anterior and parietal regions of the dummy's head contacted the tatami (judo mat). Subsequently, most of the body weight was applied, with the neck experiencing the highest compression. However, in Osoto-gari and Ouchi-gari, the occipital region of the dummy's head contacted the tatami. Significantly higher values of both Nij (median 0.68) and beam criterion (median 0.90) corresponding to a 34.7% to 37.1% risk of neck injury with an abbreviated injury scale score ≥2 were shown in Seoi-nage than in either Ouchi-gari or Osoto-gari. In judo, when thrown by the Seoi-nage technique, serious neck injuries can occur as a result of neck compression that occurs when the head contacts the ground.

Middle meningeal artery embolization for chronic subdural hematoma with high risk of recurrence: A single institution experience.

BACKGROUND: Middle meningeal artery (MMA) embolization can be a treatment option for selected cases of chronic subdural hematoma (CSDH) patients. However, appropriate timing of this procedure or the conditions to be considered are still not standardized. METHODS: Between 2008 and 2018, 18 symptomatic CSDH patients underwent MMA embolization at our institution. The timing of embolization and the risk factors for recurrence of CSDH, the recurrence rate after an embolization, and the complication were thoroughly reviewed. RESULTS: Of the 18 cases, 16 patients were male. The median age at MMA embolization was 78.5 years (range, 66-98 years). The median follow-up period were eight months (range, 2-53 months). Possible risk factors for CSDH recurrence harbored by those patients were age > 74 yrs (10), brain atrophy (4), separated hematoma (3), coagulopathy (3), anticoagulant administration (3), and thrombocytopenia (1). No recurrence or complication was observed in any of the patients after the embolization. CONCLUSIONS: MMA embolization is effective and safe in preventing recurrence of CSDH with high risk of recurrence, and could be a standard treatment for such cases.

Ukemi Technique Prevents the Elevation of Head Acceleration of a Person Thrown by the Judo Technique 'Osoto-gari'.

Biomechanical analysis was performed to evaluate the effectiveness of mastering ukemi in preventing severe head injury in judo. One judo expert (tori) threw another judo expert (uke) with a skilled break-fall (ukemi) four times. We obtained kinematic data of uke with a digital video camera. Both translational and rotational accelerations were measured with a six-degree-of-freedom sensor affixed to uke's forehead. When Osoto-gari was performed, uke fell backward and his arm made contact with the tatami; the translational and rotational accelerations rose to peak values. The peak resultant translational and rotational accelerations were respectively 10.3 ± 1.6 G and 679.4 ± 173.6 rad/s2 (mean ± standard deviation). Furthermore, when comparing the values obtained for the judo experts with those obtained using an anthropomorphic test device (ATD: the POLAR dummy) that did not perform ukemi, both the peak resultant translational (P = 0.021) and rotational (P = 0.021) accelerations of uke were significantly lower than those for the ATD, whose head struck the tatami. Additionally, there was no significant difference among the three axis directions for either translational (ax: 7.4 ± 0.2, ay: 8.5 ± 2.1, az: 7.2 ± 0.8 G) or rotational (αx: 576.7 ± 132.7, αy: 401.0 ± 101.6, αz: 487.8 ± 66.6 rad/s2) acceleration. We confirmed that performing correct ukemi prevented the elevation of head acceleration by avoiding head contact with the tatami when a judoka is thrown by Osoto-gari. Judoka should therefore undertake intensive practice after they have acquired ukemi skills.

Biomechanical Analysis of the Head Movements of a Person Thrown by the Judo Technique 'Seoi-nage'.

The present study examined the kinematics and biomechanical parameters of the head of a person thrown forward by the judo technique 'Seoi-nage'. A judo expert threw an anthropomorphic test device (the POLAR dummy) five times. Kinematics data were obtained with a high-speed digital video camera. Linear and angular accelerations of the head were measured by accelerometers mounted at the center of gravity of the dummy's head. When Seoi-nage was performed, the dummy fell forward accompanied by contacting the anterior parietal regions of the head to the tatami, and the linear and angular accelerations of most axes reached peak values when the head contacted the tatami. Peak resultant linear and angular accelerations were 20.3 ± 9.8 G and 1890.1 ± 1151.9 rad/s2, respectively (means ± standard deviation). Peak values in linear and angular acceleration did not significantly differ between the three directional axes. Absolute angular accelerations in all axes observed in Seoi-nage were high and the resultant value was approximately equal to the already reported in Ouchi-gari, one of the predominant techniques causing judo-related acute subdural hematoma. However, the remarkable increase of linear acceleration in the longitudinal direction and/or angular acceleration in the sagittal plane, as previously reported in techniques being thrown backward (i.e., Ouchi-gari and Osoto-gari), was not detected. The likely mechanism of acute subdural hematoma caused by Seoi-nage is that a large angular acceleration causes large strains and deformations of the brain surface and subsequent rupture of cortical vessels.

Fractionation of the stable carbon isotope ratio of essential fatty acids in zebrafish Danio rerio and mud snails Bellamya chinensis.

Fractionation of stable carbon (C) isotopes in the essential fatty acids 18:2n-6, 18:3n-3, 20:4n-6, 20:5n-3, and 22:6n-3 was investigated in the zebrafish Danio rerio and the mud snail Bellamya chinensis fed the same two diets. These diets differed in essential fatty acid compositions: (1) TetraMin contained all five fatty acids, and (2) Chlorella contained only two, 18:2n-6 and 18:3n-3. On average, the isotopic fractionation was -0.5 ± 0.9 ‰ for 18:2n-6 and 18:3n-3 for all experiments, indicating that the fractionation of these essential fatty acids was negligible. However, the isotopic fractionation of 20:4n-6, 20:5n-3, and 22:6n-3 varied greatly between species and between diets. The isotopic fractionation of the Chlorella diet was -0.2 and -6.9 ‰ for zebrafish and mud snail, but 4.2 and -1.3 ‰, respectively, when these consumers were fed TetraMin. This variation could be explained by the different amount of assimilation and the biosynthesis of these fatty acids from their precursors (i.e., 18:2n-6 and 18:3n-3). These results indicate that the isotopic composition of C20 and C22 essential fatty acids was strongly influenced by the fatty acid composition in the diets. Thus the stable C isotope ratios of C18 essential fatty acids in consumers are more useful as dietary tracers in food web studies.

Biomechanical analysis of acute subdural hematoma resulting from judo.

This study investigated biomechanical mechanisms of acute subdural hematoma caused by judo and sought preventive measures to reduce injury. A Japanese judo expert repeatedly threw an anthropometric test device using two throwing techniques, Osoto-gari and Ouchi-gari. Linear and angular accelerations of the head were measured. Both throwing techniques resulted in the dummy falling backwards, with the occipital area of the head contacting the mat, and peak linear and angular accelerations being observed when the head contacted the mat. For linear acceleration, the posterior-anterior direction showed the greatest force (41.0 ± 2.6 G using Osoto-gari, and 86.5 ±4.3 G using Ouchi-gari). For angular acceleration, values for sagittal plane rotation were greatest among the three directions measured (3315 ± 168 rad/s(2) using Osoto-gari, and 1328 ± 201 rad/s(2) using Ouchi-gari). We concluded that occipital head contact produced the most forceful longitudinal linear and sagittal plane angular accelerations; subsequent stretches and ruptures of parasagittal bridging veins resulting in acute subdural hematoma. As severe head injuries can result if a person's head comes into contact with the mat, offensive throwing techniques should be restricted to participants able to sufficiently demonstrate the Ukemi technique.

Rotational acceleration during head impact resulting from different judo throwing techniques.

Most severe head injuries in judo are reported as acute subdural hematoma. It is thus necessary to examine the rotational acceleration of the head to clarify the mechanism of head injuries. We determined the rotational acceleration of the head when the subject is thrown by judo techniques. One Japanese male judo expert threw an anthropomorphic test device using two throwing techniques, Osoto-gari and Ouchi-gari. Rotational and translational head accelerations were measured with and without an under-mat. For Osoto-gari, peak resultant rotational acceleration ranged from 4,284.2 rad/s(2) to 5,525.9 rad/s(2) and peak resultant translational acceleration ranged from 64.3 g to 87.2 g; for Ouchi-gari, the accelerations respectively ranged from 1,708.0 rad/s(2) to 2,104.1 rad/s(2) and from 120.2 g to 149.4 g. The resultant rotational acceleration did not decrease with installation of an under-mat for both Ouchi-gari and Osoto-gari. We found that head contact with the tatami could result in the peak values of translational and rotational accelerations, respectively. In general, because kinematics of the body strongly affects translational and rotational accelerations of the head, both accelerations should be measured to analyze the underlying mechanism of head injury. As a primary preventative measure, throwing techniques should be restricted to participants demonstrating ability in ukemi techniques to avoid head contact with the tatami.

Simple strategy to prevent severe head trauma in Judo.

To determine whether the use of an under-mat has an effect on impact forces to the head in Judo, a Judo expert threw an anthropomorphic test device using the Osoto-gari and Ouchi-gari techniques onto a tatami (judo mat) with and without an under-mat. Head acceleration was measured and the head injury criterion (HIC) values with or without under-mat were compared. The use of an under-mat significantly decreased (p = 0.021) the HIC values from 1174.7 ± 246.7 (without under-mat) to 539.3 ± 43.5 in Ouchi-gari and from 330.0 ± 78.3 (without under-mat) to 156.1 ± 30.4 in Osoto-gari. The use of an under-mat simply reduces impact forces to the head in Judo. Rule changes are not necessary and the enjoyment and health benefits of Judo are maintained.

Altered blood flow distribution in the rat spinal cord under chronic compression.

STUDY DESIGN: Sham-operation-controlled animal study to assess alterations in blood flow in the spinal cord in a chronic compression model. Laboratory investigation. OBJECTIVE: Cervical myelopathy is a common cause of disability in elderly patients. Hypothesis was made that ischemia subsequent to the spinal cord compression plays an important role in the pathogenesis of the spinal cord dysfunction. This study was undertaken to assess alterations in the blood flow of the spinal cord under chronic compression in a rat model. SUMMARY OF BACKGROUND DATA: Histologic study of spinal cord from patients with spondylotic myelopathy showed ischemic tissue changes. Experimentally, spinal cord hypoperfusion in combination with chronic spinal cord compression induced myelopathy in dogs. We previously showed that chronic compression of the spinal cord in rats produces gradual deterioration of mobility of the animals accompanied by cord tissue degeneration compatible with ischemic changes. METHODS: Chronic compression of the cervical spinal cord was implemented by implantation of a thin urethane polymer sheet under the C5-C6 laminae, which expands by absorbing tissue water over 48-72 hours. The control group underwent sham operation. Twelve weeks later, blood flow to the C3-C4 and C5-C6 spinal cord segments were measured by fluorescent microsphere methods. RESULTS: In the control group, the blood flow in the C5-C6 segment was larger than C3-C4 segment. In the compression group, the blood flow in the C5-C6 was significantly reduced compared to the C3-C4 segment. CONCLUSION: Under chronic focal spinal cord compression, there was a decrease of the blood flow in the compressed segment in comparison to the rostral segment. Our data are compatible with the hypothesis that alteration in the spinal cord blood flow contributes to pathogenesis of myelopathy.

Is postoperative CT scanning predictive of subdural electrode placement complications in pediatric epileptic patients?

AIMS: To understand the reliability of postoperative CT scans to predict the development of intracranial hemorrhagic complications associated with subdural electrode implants for monitoring intractable seizure, we reviewed the data of a consecutive series of children treated at our institution. METHODS: Forty children (mean age: 11.4 years) with subdural electrode implants were reviewed. The immediate postoperative CT scans were evaluated for the presence of hemorrhagic complications and/or brain swelling resulting in a midline shift. RESULTS: Twenty-six patients (65%) presented a postoperative midline shift (range = 2-10 mm; mean shift = 4.0 mm). Two children had a midline shift of >5 mm. Two patients with a shift of <5 mm at the first CT scan required a repeat craniotomy. These patients experienced worsening neurologic symptoms in a delayed fashion on postoperative days 1 and 4, respectively. This was correlated to an increase in midline shift of >5 mm. CONCLUSIONS: Subdural electrode implants in children are safe. The presence of a midline shift of <5 mm is common postoperatively. The presence and extension of the midline shift at the first CT scan does not seem to be predictive of the development of symptomatic complications with a mass effect. Complications happened in a delayed fashion.

[Basic investigation of software named "Heart Risk View" to estimate the probability of cardiac events, for the purpose of evaluating the availability in clinical practice].

We validated Heart Risk View (HRV) software for estimating cardiac event probability in patients with suspected ischemic heart disease. This software is based on the results of the J-ACCESS (Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT). The HRV software can calculate stress summed scores (SSS), summed rest scores (SRS), and summed difference scores automatically using the 5 point, 20 or 17 segment model of myocardial SPECT images. It can also calculate the probability of cardiac events occurring in patients within 3 years using SSS and parameters obtained from the results of gated SPECT. Changing the threshold of % uptake for determining SPECT scores elevated the agreement of SSS (kappa = 0.269 to 0.657). Cardiac event probability calculated from Perfusion and Function Assessment for Myocardial SPECT (p-FAST) using end systolic volume (ESV), tended to be higher than that calculated from Quantitative Gated SPECT software (QGS). In contrast, cardiac event probability calculated from QGS and p-FAST using left ventricle ejection fraction (LVEF) closely agreed.

Electroencephalography-guided resection of dysembryoplastic neuroepithelial tumor: case report.

A 3-year-old girl presented with a dysembryoplastic neuroepithelial tumor in the right cingulate gyrus manifesting as epilepsy refractory to anticonvulsant medication. Computed tomography and magnetic resonance imaging revealed a cystic tumor in the right cingulate gyrus. The tumor was removed under intraoperative electrocorticography guidance. Abnormal spikes recorded adjacent to the tumor disappeared immediately after total removal. Histological examination showed a multinodular, multicystic structure, satisfying the criteria for the diagnosis of dysembryoplastic neuroepithelial tumor. She has remained seizure-free for more than 4 years without complications. In this case, intraoperative electrocorticography was very useful to identify the possible focus and prevent unnecessary resection of the adjacent tissue. Total removal of the tumor resulted in a dramatic reduction of seizure activity.

Comparison of numerical change of epidermal growth factor receptor gene among pre- and postradiation glioma, and gliosis, and its clinical use.

Surgery with following chemoradiotherapy is the mainstream glioma treatment. In the course of postradiation events, however, it is sometimes difficult for neurosurgeons, radiologists, and pathologists to discriminate tumor recurrence from radiation necrosis. The epidermal growth factor receptor (EGFR) gene, on chromosome 7, is known to gain in copy number frequently in high-grade gliomas. The authors applied the fluorescence in situ hybridization (FISH) method to observe the gene's numerical status in pre- and postradiation glioma samples to elucidate whether this technique is useful in the discrimination of glioma recurrence from radiation necrosis. When 15 postradiation glioma samples and 4 postradiation nonglioma samples were tested, all the recurrent glioma tissue harbored numerical aberrations of the gene, whereas no abnormality could be observed in necrosis or in nonglioma gliosis. FISH could even prove a residual glioma cell in a gliotic tissue taken by needle biopsy after gamma-knife radiosurgery, which had been executed on a supposed metastatic brain tumor. FISH is considered to be of help in accurate diagnosis, especially when the usual histopathological diagnosis is difficult because of radiation effects or small sample size.

Locally advanced and metastatic breast cancer with cartilaginous and/or osseous metaplasia showing excellent response to chemotherapy.

Breast cancer with cartilaginous and/or osseous metaplasia is considered a rare disease, but several cases have been reported recently. We report a case of breast cancer with cartilaginous and/or osseous metaplasia that was StageIV,(T4bN0M1b (PUL)), on the basis of the Japanese General Rules for Clinical and Pathological Recording of Breast Cancer, which responded well to chemotherapy. A 58-year-old women visited our hospital with a chief complaint of a palpable breast mass that had increased in size in March 2002. It was 20 x 15 x 14 cm and occupied the entire right breast. Chest computed tomography (CT) demonstrated multiple lung metastases. Histology of the biopsy specimens revealed a spindle-shaped cell carcinoma. It was ER(-), PgR(-), and HER2/neu Score 0. CAF was given to the patient as preoperative chemotherapy. Five cycles of treatment yielded improvement at the primary site and improvement of the metastatic lung lesions, which was judged as a partial response. Subsequently, one cycle of weekly paclitaxel 80 mg/m2 and oral administration of 5'-DFUR 800 mg/day were given. In November 2002, the patient underwent a right simple mastectomy with whole-layer skin grafting from the abdomen. The final pathological diagnosis was a rare type of breast cancer with cartilaginous and/or osseous metaplasia. Preoperative chemotherapy had caused necrosis in most of the tumor cells, and the efficacy was judged as Grade 2. From the third week postoperatively, weekly paclitaxel (80 mg/m2) was given. Six months after the operation, the multiple lung metastases were completely eliminated and new metastasis to liver or bone or local recurrence have not been observed.

Axilloaxillary bypass for the treatment of subclavian artery stenosis complicated by bilateral common carotid artery occlusion: technical case report.

OBJECTIVE AND IMPORTANCE: We successfully treated a patient with stenosis of the left subclavian artery, complicated by bilateral common carotid artery occlusion, via axilloaxillary bypass surgery. CLINICAL PRESENTATION: A 67-year-old patient with a history of hypertension and cerebral infarction underwent neck irradiation for treatment of a vocal cord tumor. Three months later, he began to experience transient tetraparesis several times per day. The blood pressure measurements for his right and left arms were different. Supratentorial blood flow was markedly low. The common carotid arteries were bilaterally occluded, and the right vertebral artery was hypoplastic. Therefore, only the left vertebral artery contributed to the patient's cerebral circulation; his left subclavian artery was severely stenotic. INTERVENTION: The patient underwent axilloaxillary bypass surgery because the procedure avoids thoracotomy or sternotomy, manipulation of the carotid artery, and interruption of the vertebral artery blood flow. The patient has been free of symptoms for more than 5 years. CONCLUSION: Neurosurgeons should be aware that extra-anatomic bypass surgery is an effective treatment option for selected patients with cerebral ischemia.

Postischemic hypothermia inhibits the generation of hydroxyl radical following transient forebrain ischemia in rats.

A small reduction of body temperature during reperfusion following cerebral ischemia has been known to ameliorate neuronal injury. However, the mechanisms underlying postischemic hypothermia-induced neuroprotection are poorly understood. The burst of reactive oxygen species (ROS) formation that occurs during reperfusion has been documented to be involved in ischemic neuronal degeneration. In this study, we investigated the effect of postischemic hypothermia on ROS production following transient forebrain ischemia using an in vivo microdialysis technique. Forebrain ischemia was induced by bilateral carotid artery occlusion combined with hemorrhagic hypotension for 20 min in male Wistar rats. The body temperature was kept at 37 degrees C during ischemia and controlled at either 32 degrees C or 37 degrees C after reperfusion. The amount of hydroxyl radical produced in striatum was evaluated by measurement of 2,3- and 2,5-dihydroxybenzoic acid (DHBA), which is generated by salicylate hydroxylation. We also measured the extracellular concentration of xanthine, while determining striatal blood flow by the hydrogen clearance technique. In animals whose postischemic body temperature was maintained at 37 degrees C, the levels of 2,3- and 2,5-DHBA significantly increased after reperfusion. The peak levels of 2,3- and 2,5- DHBA were 2.9-fold and 2.7-fold increased above the corresponding baseline values, respectively. Postischemic hypothermia completely inhibited the hydroxyl radical formation. Likewise, xanthine formation was also inhibited by postischemic hypothermia. In contrast, striatal cerebral blood flow was not altered by temperature modulation during reperfusion. These results suggest that inhibition of ROS production accompanied with suppression of xanthine formation is implicated in the neuroprotection of postischemic hypothermia.

Dural arteriovenous fistula and progressive conus medullaris syndrome as complications of lumbar discectomy. Case report.

A case of a dural arteriovenous fistula (DAVF) that developed at the site of nerve root sleeve damage as a result of lumbar disc extrusion is reported. A 60-year-old man who had undergone lumbar discectomy 3 years previously for severe left-sided sciatica and L5-S1 disc herniation presented with progressive gait disturbance. After the initial surgery, the symptoms resolved. Fourteen months after the operation, however, he started to experience dysesthesias in both legs and progressive gait and urinary disturbances. Physical examination revealed a weakness of the anterior tibialis and the gastrocnemius muscles, as well as decreased contractility of the anal sphincter and marked sacral hypesthesia. Magnetic resonance (MR) imaging revealed swelling and a T2 signal elongation in the conus medullaris; angiography demonstrated arteriovenous dural shunting between the left lateral sacral artery and the left S-1 radicular vein at the site of the previous operation. Surgery was conducted to excise the DAVF on the S-1 nerve root sleeve and an arterialized intradural vein on the root. The procedure resulted in resolution of the symptoms and disappearance of the abnormal angiographically and MR imaging-documented anomalies. This is the first report of a DAVF in which progressive conus myelopathy developed after a lumbar discectomy.