New rat model of spinal cord infarction with long-lasting functional disabilities generated by intraspinal injection of endothelin-1.

BACKGROUND: The current method for generating an animal model of spinal cord (SC) infarction is highly invasive and permits only short-term observation, typically limited to 28 days. OBJECTIVE: We aimed to establish a rat model characterised by long-term survival and enduring SC dysfunction by inducing selective ischaemic SC damage. METHODS: In 8-week-old male Wistar rats, a convection-enhanced delivery technique was applied to selectively deliver endothelin-1 (ET-1) to the anterior horn of the SC at the Th13 level, leading to SC infarction. The Basso, Beattie and Bresnahan (BBB) locomotor score was assessed for 56 days. The SC was examined by a laser tissue blood flowmeter, MRI, immunohistochemistry, triphenyl tetrazolium chloride (TTC) staining, Western blots and TUNEL staining. RESULTS: The puncture method was used to bilaterally inject 0.7 µL ET-1 (2.5 mg/mL) from the lateral SC into the anterior horns (40° angle, 1.5 mm depth) near the posterior root origin. Animals survived until day 56 and the BBB score was stably maintained (5.5±1.0 at day 14 and 6.2±1.0 at day 56). Rats with BBB scores ≤1 on day 1 showed stable scores of 5-6 after day 14 until day 56 while rats with BBB scores >1 on day 1 exhibited only minor dysfunction with BBB scores >12 after day 14. TTC staining, immunostaining and TUNEL staining revealed selective ischaemia and neuronal cell death in the anterior horn. T2-weighted MR images showed increasing signal intensity at the SC infarction site over time. Western blots revealed apoptosis and subsequent inflammation in SC tissue after ET-1 administration. CONCLUSIONS: Selective delivery of ET-1 into the SC allows for more precise localisation of the infarcted area at the targeted site and generates a rat SC infarction model with stable neurological dysfunction lasting 56 days.

Sensory and physicochemical characteristics of Japanese jidori chicken (Choshu-Kurokashiwa) and broiler thigh meat: Effect of cooking procedure.

This study aimed to investigate the effects of various cooking procedures on the sensory and physicochemical properties of Japanese jidori chicken (Choshu-Kurokashiwa) and broiler thigh meat. Thigh meats were cooked using three different procedures: grilling, boiling, and deep-frying. Subsequently, we performed sensory evaluation by a trained panel and instrumental analysis on both raw and cooked meat to determine changes in pH, shear force value, cooking loss, nucleotide metabolite contents, and proximate, free amino acid, and fatty acid composition. From the sensory evaluation, "springiness" and "chewiness" were found to be characteristics of Choshu-Kurokashiwa thigh meat among all cooking procedures. In terms of "juiciness" and "sulfur flavor," chicken breed and cooking procedure interacted, and these were considerably higher in Choshu-Kurokashiwa meat than in broiler meat only when boiling. In the instrumental analysis, Choshu-Kurokashiwa meat showed a considerably higher shear force value and lower free amino acid content than broiler meat, regardless of the cooking procedure used. Again, in terms of cooking loss, chicken breed and cooking procedure interacted, and this was considerably lower in Choshu-Kurokashiwa meat than in broiler meat only when boiling. These results showed that cooking procedure should be considered when describing the sensory characteristics of jidori thigh meat.

Theoretical Study on the Open-Shell Electronic Structure and Electron Conductivity of [18]Annulene as a Molecular Parallel Circuit Model.

Herein, the electron conductivities of [18]annulene and its derivatives are theoretically examined as a molecular parallel circuit model consisting of two linear polyenes. Their electron conductivities are estimated by elastic scattering Green's function (ESGF) theory and density functional theory (DFT) methods. The calculated conductivity of the [18]annulene does not follow the classical conductivity, i.e., Ohm's law, suggesting the importance of a quantum interference effect in single molecules. By introducing electron-withdrawing groups into the annulene framework, on the other hand, a spin-polarized electronic structure appears, and the quantum interference effect is significantly suppressed. In addition, the total current is affected by the spin polarization because of the asymmetry in the coupling constant between the molecule and electrodes. From these results, it is suggested that the electron conductivity as well as the quantum interference effect of π-conjugated molecular systems can be designed using their open-shell nature, which is chemically controlled by the substituents.

Dynamic Changes of Gene Expression in Mouse Mural Trophectoderm Regulated by Cdx2 During Implantation.

Implantation of the blastocyst into the uterus is a specific and essential process for mammalian embryonic development. In mice, implantation is initiated from the mural trophectoderm of the blastocyst and the mTE controls implantation progression by acquiring the ability to attach and invade into the endometrium while differentiating into primary trophoblast giant cells. Nevertheless, it remains largely unclear when and how the mTE differentiates and acquires this ability during implantation. Here, by RNA sequencing analysis with the pre- and peri-implantation mTE, we show that the mTE undergoes stage-specific and dynamic changes of gene expression during implantation. We also reveal that the mTE begins down-regulating Cdx2 and up-regulating differentiation marker genes during the peri-implantation stage. In addition, using trophectoderm (TE) -specific lentiviral vector-mediated gene transduction, we demonstrate that TE-specific Cdx2 overexpression represses differentiation of the mTE into the primary trophoblast giant cells. Moreover, we reveal that TE-specific Cdx2 overexpression also represses the up-regulation of cell adhesion- and migration-related genes, including Slc6a14, Slc16a3, Itga7, Itgav and Itgb3, which are known to regulate migration of trophectoderm cells. In particular, the expression of Itgb3, an integrin subunit gene, exhibits high inverse correlation with that of Cdx2 in the TE. Reflecting the down-regulation of the genes for TE migration, TE-specific Cdx2 overexpression causes suppression of the blastocyst outgrowth in vitro and abnormal progression of implantation in vivo. Thus, our results specify the time-course changes of global gene expression in the mTE during implantation and uncover the significance of Cdx2 down-regulation for implantation progression.

Plasma tRNA derivatives concentrations for detecting early brain damage in patients with acute large vessel occlusion and predicting clinical outcomes after endovascular thrombectomy.

OBJECTIVE: Transfer RNA (tRNA) is involved in the acute stress response, which results in conformational changes and subsequent fragmentation. Using an antibody against tRNA-specific modified nucleoside 1-methyladenosine, we can selectively detect blood tRNA derivatives from damaged tissues, including neuronal tissue, which serves as a potential marker of early tissue damage. This preliminary study aimed to investigate the correlation between tRNA derivatives and clinical outcomes in patients with acute anterior large vessel occlusion, especially those who underwent endovascular thrombectomy (EVT). METHODS: Patients with acute ischemic stroke due to anterior circulation large vessel occlusion were prospectively enrolled in this study. Plasma tRNA derivatives were measured using an enzyme-linked immunosorbent assay with an anti-modified nucleoside 1-methyladenosine antibody. RESULTS: Seventeen patients were included. The plasma tRNA derivatives concentrations on admission increased significantly, corresponding to the infarction size (r = 0.492, p = 0.038), and were associated with clinical outcomes (p = 0.00309). A good clinical outcome (90-day modified Rankin scale score: 0-2) was achieved in seven patients (41.2%), and all had undergone EVT. Among these patients, tRNA derivatives concentrations were the only preoperative predictor, which was associated with good outcomes (modified Rankin scale score: 0-2) and was significantly lower than those with poor outcomes (modified Rankin scale score: 3-6) (p = 0.0333). Receiver operating characteristic analysis revealed that a tRNA derivative value of ≤ 142.0 mg/mL was associated with good clinical outcomes, with a sensitivity of 85.7% and a specificity of 100% (area under the curve, 0.952; 95% confidence interval: 0.82-1). CONCLUSION: tRNA derivatives concentration may be a sensitive marker of early brain damage in patients with acute large vessel occlusion. Patients with low levels of tRNA derivatives on arrival are likely to benefit from thrombectomy and have the potential to achieve good clinical outcomes.

Meat consumption and consumer attitudes in Japan: An overview.

Among Asian countries, Japan has the shortest history of eating meat in its food culture. It was only after 2007 that household fresh meat consumption surpassed fresh fish consumption in Japan. Although it was forecast that slowing population and economic growth would limit the demand for meat, household meat consumption in 2020 increased remarkably from that in 2019, perhaps due to COVID-19. Meat consumption has regional variations within Japan attributable to historical background. Japanese consumers prefer domestically produced meat and focus on the visual characteristics of meat, in particular marbling. Extrinsic factors such as information also contribute to Japanese consumers' meat choices more than the quality of the meat. Although Japanese consumers are concerned about the safety of meat, reassurance from appropriate inspection will restore their purchasing intention. Novel factors such as animal welfare and environment-friendly production are also recognized in Japan. Also notable is that wild animal meat consumption is beginning to increase in recent years.

Diversity of Japanese consumers' requirements, sensory perceptions, and eating preferences for meat.

Japanese consumers are generally characterized as preferring high marbling in beef and pork and choosing domestic products. However, the Japanese food market is not homogenous. Understanding the diversity of Japanese consumers will provide benefits for the optimization of meat production and distribution in Japan. This article focuses on three factors affecting purchasing decisions and eating satisfaction, namely, requirements, sensory perception, and eating preferences, in order to understand the diversity of Japanese consumers in a simplified manner. Diversity was observed in Japanese consumers in all three of these factors (requirements, perception, and preference) using a questionnaire survey, sensory and biological procedures, and an eating preference test. These diversities are due to not only sociodemographic characteristics but also biological and physiological factors, background culture, and individual attitudes and criteria. Although consumer variation based on sociodemographic characteristics is of course important, it is equally important to understand diversity by focusing on the individual differences among consumers.

Estimation of discrimination threshold for emulsified chicken oil in chicken broth.

Although fat content affects the texture and flavor of meat and meat products, the fat discrimination thresholds are unknown. This study aimed to elucidate the discrimination threshold of fat in meat products using broth from chicken thigh meat as a meat taste model. In Experiment 1, triangle tests were conducted between 1%, 0.2%, 0.04%, and 0.008% (w/v) chicken oil-supplemented broth and broth without chicken oil. The results indicated the discrimination threshold to be between 0.04% and 0.008% (w/v). In Experiment 2, similar triangle tests were conducted using oil supplementation at 0.1%, 0.0333%, 0.0111%, and 0.0037% to refine the discrimination threshold. Logistic regression analysis revealed that the discrimination threshold of emulsified chicken oil in chicken broth was 0.0387% (w/v). We demonstrated that chicken oil made a sensory difference in chicken broth at a low concentration and indicates that the chicken oil strongly affects the sensory characteristics of chicken broth.

Giant Intraosseous Meningioma Associated with Calvarial Hyperostosis and Subcutaneous Invasion: Case Reports and Literature Review.

Most meningiomas grow intracranially, and primary intraosseous meningioma is rarely reported. We present two rare surgical cases of giant intraosseous meningothelial meningioma. The first patient was a 35-year-old male with parietal skull deformity without neurological symptoms. Total resection was successful. The origin was the parasagittal intraosseous layer, and the superior sagittal sinus was partially opened. The second patient was a 20-year-old female with a slightly upward protrusion of the frontal skull without pain or neurological deficits. The lesion was totally resected, and the origin was the parasagittal intraosseous layer invading into the dura matter and subcutaneous layer. The clinical management of these cases presented a surgical challenge because of detachment and repair from venous sinuses. The current report provides surgical tips for such rare diseases and is a good reference for the future treatment of similar diseases.

Distribution of dietary protein intake in daily meals influences skeletal muscle hypertrophy via the muscle clock.

The meal distribution of proteins throughout the day is usually skewed. However, its physiological implications and the effects of better protein distribution on muscle volume are largely unknown. Here, using the two-meals-per-day feeding model, we find that protein intake at the early active phase promotes overloading-induced muscle hypertrophy, in a manner dependent on the local muscle clock. Mice fed branched-chain amino acid (BCAA)-supplemented diets at the early active phase demonstrate skeletal muscle hypertrophy. However, distribution-dependent effects are not observed in ClockΔ19 or muscle-specific Bmal1 knockout mice. Additionally, we examined the relationship between the distribution of proteins in meals and muscle functions, such as skeletal muscle index and grip strength in humans. Higher muscle functions were observed in subjects who ingested dietary proteins mainly at breakfast than at dinner. These data suggest that protein intake at breakfast may be better for the maintenance of skeletal muscle mass.

H3K27M and TERT promoter mutations are poor prognostic factors in surgical cases of adult thalamic high-grade glioma.

BACKGROUND: Thalamic high-grade gliomas (HGGs) are rare tumors with a dismal prognosis. H3K27M and telomerase reverse transcriptase promoter (TERTp) mutations reportedly contribute to poor prognoses in HGG cases. We investigated the outcomes of surgically treated adult thalamic HGGs to evaluate the prognostic significance of H3K27M and TERTp mutations. METHODS: We retrospectively analyzed 25 adult patients with thalamic HGG who underwent maximum surgical resection from January 1997 to March 2020. The histological and molecular characteristics, progression-free survival (PFS), and overall survival (OS) of the patients were compared. For molecular characteristics, target sequencing was used to determine the H3F3A, HIST1H3B, and TERTp mutations. RESULTS: H3K27M mutations were detected in 12/25 (48.0%) patients. TERTp mutations were not detected in H3K27M-mutant gliomas but were detected in 8/13 (61.5%) of H3 wild-type gliomas. Although it was not significant, H3K27M-mutant gliomas tended to have a shorter PFS (6.7 vs 13.1 months; P = .2928) and OS (22.8 vs 24.4 months; P = .2875) than H3 wild-type gliomas. Moreover, the prognosis of TERTp-mutant gliomas was as poor as that of H3K27M-mutant gliomas. Contrary, 5 gliomas harboring both H3 and TERTp wild-type showed a better median PFS (59.2 vs 6.4 months; P = .0456) and OS (71.8 vs 24.4 months; P = .1168) than those harboring H3K27M or TERTp mutations. CONCLUSIONS: TERTp-mutant gliomas included in the H3 wild-type glioma group limited patient survival as they exhibited an aggressive course similar to H3K27M-mutant gliomas. Comprehensive molecular work-up for the H3 wild-type cases may further confirm this finding.

Standard values for temporal muscle thickness in the Japanese population who undergo brain check-up by magnetic resonance imaging.

BACKGROUND: Skeletal muscle mass is an important factor for various diseases' outcomes. The psoas muscle cross-sectional area on the abdominal computed tomography (CT), gait speed, and handgrip strength is used to measure it. However, it is difficult to measure the neurological patients' muscle mass or function because (1) we do not perform abdominal CT. (2) Such patients have impaired consciousness, gait disturbance, paresis, and need of rest. Temporal muscle thickness (TMT) on magnetic resonance imaging (MRI) is now attractive for skeletal muscle volume indicator, but the reference values are not established. We herein investigated the standard value of the Japanese TMT using the brain check-up database by MRI. METHODS: We retrospectively investigated 360 Japanese individuals from two institutions between 2017 and 2019. We measured TMT on the T1-weighted images in the previously reported way. The associations between TMT and other variables were analyzed. RESULTS: TMT of 214 women and 146 men, ranging from 35 to 84 years old, was investigated. TMT ranged from 3.69 to 16.90 mm. Mean TMT values were significantly higher in men compared to women except for the over 70-year-old cohort. TMT was correlated to weight and body mass index in both sexes. CONCLUSION: This is the first retrospective study on the standard TMT values from the Japanese brain check-up database. Our results were just reference values, but these would be useful for further investigation in other neurosurgical and neurological diseases regarding muscle volume or sarcopenia.

Oocyte-specific gene knockdown by intronic artificial microRNAs driven by Zp3 transcription in mice.

Conditional knockout technology is a powerful tool for investigating the spatiotemporal functions of target genes. However, generation of conditional knockout mice involves complicated breeding programs and considerable time. A recent study has shown that artificially designed microRNAs (amiRNAs), inserted into an intron of the constitutively expressed gene, induce knockdown of the targeted gene in mice, thus creating a simpler method to analyze the functions of target genes in oocytes. Here, to establish an oocyte-specific knockdown system, amiRNA sequences against enhanced green fluorescent protein (EGFP) were knocked into the intronic sites of the Zp3 gene. Knock-in mice were then bred with EGFP transgenic mice. Our results showed that Zp3-derived amiRNA successfully reduced EGFP fluorescence in the oocytes in a size-dependent manner. Importantly, knockdown of EGFP did not occur in somatic cells. Thus, we present our knockdown system as a tool for screening gene functions in mouse oocytes.

A Transcranial Magnetic Stimulation Trigger System for Suppressing Motor-Evoked Potential Fluctuation Using Electroencephalogram Coherence Analysis: Algorithm Development and Validation Study.

BACKGROUND: Transcranial magnetic stimulation (TMS), when applied over the primary motor cortex, elicits a motor-evoked potential (MEP) in electromyograms measured from peripheral muscles. MEP amplitude has often been observed to fluctuate trial to trial, even with a constant stimulus. Many factors cause MEP fluctuations in TMS. One of the primary factors is the weak stationarity and instability of cortical activity in the brain, from which we assumed MEP fluctuations originate. We hypothesized that MEP fluctuations are suppressed when TMS is delivered to the primary motor cortex at a time when several electroencephalogram (EEG) channels measured on the scalp are highly similar in the frequency domain. OBJECTIVE: We developed a TMS triggering system to suppress MEP fluctuations using EEG coherence analysis, which was performed to detect the EEG signal similarity between the 2 channels in the frequency domain. METHODS: Seven healthy adults participated in the experiment to confirm whether the TMS trigger system works adequately, and the mean amplitude and coefficient of the MEP variation were recorded and compared with the values obtained during the control task. We also determined the experimental time under each condition and verified whether it was within the predicted time. RESULTS: The coefficient of variation of MEP amplitude decreased in 5 of the 7 participants, and significant differences (P=.02) were confirmed in 2 of the participants according to an F test. The coefficient of variation of the experimental time required for each stimulus after threshold modification was less than that without threshold modification, and a significant difference (P<.001) was confirmed by performing an F test. CONCLUSIONS: We found that MEP could be suppressed using the system developed in this study and that the TMS trigger system could also stabilize the experimental time by changing the triggering threshold automatically.

Intractable Hiccups as the Primary Symptom of a Perimedullary Arteriovenous Fistula at the Craniocervical Junction.

BACKGROUND: Hiccups are a well-known short-term phenomenon in daily life. If they persist or become intractable, they may be a primary symptom of a disease. Recent studies identified the medulla oblongata as the neuroanatomic center of the hiccup reflex arc. In previous cases, an isolated lesion at the dorsal side of the medulla oblongata induced intractable hiccups. CASE DESCRIPTION: We herein describe a patient with a perimedullary arteriovenous fistula (PMAVF) at the craniocervical junction who had intractable hiccups. A 70-year-old male presented with a 3-year history of intractable hiccups that continued for a few days every week. An initial examination failed to identify the underlying cause, and neither medicine nor self-treatment attenuated his symptoms. Intracranial T2-weighted magnetic resonance imaging showed a hyperintensity area within the dorsolateral medulla and flow voids along the dorsal side of the cervical spine. Angiography revealed PMAVF fed by the left C1 radiculomedullary artery. Obliteration of the fistula was performed, after which intractable hiccups had completely disappeared within 1 week. CONCLUSIONS: This is the first case report of PMAVF at the craniocervical junction presenting with intractable hiccups that suggested a lesion in the dorsal side of the medulla. The mechanisms underlying hiccups are also discussed.

Temporal muscle thickness and area with various characteristics data of the patients with aneurysmal subarachnoid hemorrhage who underwent endovascular coiling.

These data present the characteristics of patients with subarachnoid hemorrhage who underwent endovascular coiling. We retrospectively collected data from the medical records of Iwaki City Medical Center including physiological symptoms, laboratory data, radiological data on admission, and modified Rankin Scale scores at 6 months. Our article entitled "Temporal Muscle as an Indicator of Sarcopenia is Independently Associated with Hunt and Kosnik Grade on Admission and the Modified Rankin Scale at 6 Month of Patients with Subarachnoid Hemorrhage Treated by Endovascular Coiling" was based on these data [1]. We previously reported similar small dataset of elderly patients with subarachnoid hemorrhage who underwent surgical clipping [2], [3]. However, remarkably, this is the largest and the first dataset on temporal muscle thickness or area of patients of all ages with subarachnoid hemorrhage who underwent endovascular coiling, not surgical clipping.

Efficacy of intra-arterial indocyanine green angiography for the microsurgical treatment of dural arteriovenous fistula: A case report.

BACKGROUND: In this study, we report a case of dural arteriovenous fistula (dAVF) that was successfully treated using intra-arterial indocyanine green (IA-ICG) videoangiography during open surgery. Moreover, the findings of IA-ICG videoangiography were compared with those of intraoperative digital subtraction angiography (DSA). CASE DESCRIPTION: A 72-year-old male patient with a history of hypertension, hyperlipidemia, and thrombocytosis presented with generalized seizure. DSA revealed Cognard Type III dAVF in the superior wall of the left transverse sinus, which was fed by a single artery (the left occipital artery [OA]) and drained into a single vein (the left temporal cortical vein), without drainage into a venous sinus. Since transarterial embolization was considered challenging due to the tortuosity of the left OA, surgical interruption of the shunt was performed by craniotomy. After excising the feeding artery, we were unable to observed dAVF on intraoperative DSA. However, IA-ICG videoangiography revealed the remaining shunt, which was fed by the collateral route from the feeding artery. The shunting point and draining vein were then surgically resected to eliminate the shunt. The shunt was not observed during the second IA-ICG videoangiography conducted after resection. CONCLUSION: ICG videoangiography is a better method compared with DSA in terms of visualizing fine vascular lesions. In contrast to the typical intravenous administration, selective IA-ICG can be repeatedly injected at a minimal dose. IA-ICG is a useful intraoperative tool that can be used to evaluate the elimination of the dAVF.

Temporal Muscle as an Indicator of Sarcopenia is Independently Associated with Hunt and Kosnik Grade on Admission and the Modified Rankin Scale Score at 6 Months of Patients with Subarachnoid Hemorrhage Treated by Endovascular Coiling.

OBJECTIVE: Sarcopenia is defined as the loss of skeletal muscle mass and is considered an important factor for clinical outcomes in various diseases. Recent studies have shown that temporal muscle thickness (TMT) and area (TMA) can be novel indicators of sarcopenia. We examined clinical characteristics, including TMT and TMA, of patients with subarachnoid hemorrhage (SAH) treated by endovascular coiling. METHODS: A retrospective analysis of 298 patients with SAH who were treated with endovascular coiling from 2009 to 2019 was conducted. Their premorbid modified Rankin Scale (mRS) score was 0-2. The association between the factors and Hunt and Kosnik (H-K) grades on admission and that between the clinical variables and mRS scores 6 months after the operation were analyzed. RESULTS: In all 298 patients with SAH, Fisher group 4 and TMA <200 mm2 were independently associated with H-K grade III-V on admission in the multivariate analysis. In 254 patients with H-K grades I-III on admission, age, H-K grade III, presence of ventriculoperitoneal shunt, presence of postoperative complications, and TMA <200 mm2 were independent factors related to poor outcomes in the multivariate analysis. CONCLUSIONS: The H-K grade on admission was independently associated with TMA. The mRS score 6 months after aneurysm treatment in patients with H-K grades I-III was also independently associated with TMA. Sarcopenia could be one of a few modifiable factors that prevent severe symptoms of SAH and improve outcomes after coiling by strengthened nutrition and physical activity.

Thoracic Dural Arteriovenous Fistula Presenting with Isolated Pseudobulbar Palsy Mimicking Brainstem Lesion.

BACKGROUND: Spinal dural arteriovenous fistulas (DAVFs) are usually associated with neurologic dysfunction adjacent to the shunt point; however, the symptoms are uncommon far from the site of the fistula. To our knowledge, this is the first report of a patient with rapidly progressive isolated pseudobulbar palsy because of thoracic DAVF. CASE DESCRIPTION: We report a patient with thoracic DAVF presenting with remote symptoms of brainstem congestion. The patient was a 36-year-old man who presented with a sudden history of vomiting, dysphagia, and flaccid weakness in the 4 limbs. Intracranial magnetic resonance (MR) imaging at a local hospital demonstrated T2 signal hyperintensity within the medulla, and he was referred to our hospital for a suspected brainstem lesion. However, cervical MR imaging revealed a dilated and tortuous perimedullary venous plexus, and spinal angiography revealed DAVF in T5-6 with a feeding artery from the intercostal artery. After obliteration of the fistula, the progression of the disease was stopped and the symptoms improved. CONCLUSIONS: Although rare, thoracic DAVFs may present symptoms resembling brainstem infarction. Prompt surgical intervention is necessary for patients with thoracic DAVF presenting with rapidly progressive pseudobulbar palsy.