Microdialysis-integrated HPLC system with dual-electrode detection using track-etched membrane electrodes for in vivo monitoring of dopamine dynamics.

A capillary high-performance liquid chromatography (HPLC) system equipped with a dual-electrode detector utilizing track-etched membrane electrodes (TEMEs) was combined with a microdialysis sampling setup. The electrochemical detector benefits from the high electrolysis efficiency of TEMEs, allowing for calibration-free coulometric detection and simplifying data analysis to determine the dopamine recovery through a dialysis probe. Additionally, this system was used for in vivo monitoring of dopamine in the right striatum of a mouse brain. Temporal changes in dopamine levels, including an exponential decay immediately after the dialysis probe insertion and an excess release of dopamine induced by a high concentration of potassium ions, confirmed the system's proper operation. Furthermore, subsequent measurements following the intraperitoneal injection of mirtazapine showed no increase in dopamine levels in the right dorsal striatum. The dual-electrode system displayed characteristic dopamine detection behavior, with anodic and cathodic peak pairs indicative of reversible electrochemical reactions. This capability facilitated the identification of the dopamine peak within the complex chromatogram of the mouse brain dialysate. The consistency between dopamine collection efficiency from standard solutions and dialysate indicated the absence of interfering electroactive substances overlapping with the dopamine peak in the chromatogram. This integrated analysis system successfully tracked temporal fluctuations in dopamine concentration within the mouse brain.

Balloon pulmonary angioplasty under awake veno-arterial extracorporeal membrane oxygenation in a patient with class III obesity with chronic thromboembolic pulmonary hypertension complicated with multiple serious comorbidities.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a chronic disease that can rapidly deteriorate into circulatory collapse when complicated by comorbidities. We herein describe a case involving a 43-year-old woman with class III obesity (body mass index of 63 kg/m2) and severe CTEPH associated with total occlusion of the left main pulmonary artery who subsequently developed circulatory collapse along with multiple comorbidities, including acute kidney injury, pulmonary tuberculosis, and catastrophic antiphospholipid syndrome. The patient was successfully treated with two sessions of rescue balloon pulmonary angioplasty with veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support under local anesthesia without sedation, at cannulation and during the V-A ECMO run, to avoid invasive mechanical ventilation. This case suggests the potential usefulness of rescue balloon pulmonary angioplasty under awake V-A ECMO support for rapidly deteriorating, inoperable CTEPH in a patient with class III obesity complicated with multiple comorbidities.

Delayed formation and rupture of intracranial aneurysm following Abiotrophia defectiva endocarditis.

Abiotrophia defectiva is a type of Streptococci and is a rare cause of infectious endocarditis. The progression and outcomes of infectious intracranial aneurysms (IIAs) associated with this species are unknown due to a limited number of reported cases. A woman in her 20s with a sudden headache had a subarachnoid haemorrhage on a head CT scan. Cerebral angiography showed an aneurysm on the right middle cerebral artery. She was diagnosed with infectious endocarditis caused by A. defectiva and underwent parent artery occlusion. Despite initiating targeted antibiotic therapy, a new IIA developed and ruptured 14 days postadmission. A second parent artery occlusion was performed on the new IIA. Following 6 weeks of continued antibiotic therapy, she underwent mitral valve repair and was discharged with no neurological symptoms. Endocarditis caused by A. defectiva can lead to the delayed formation of an IIA. Endovascular treatment was effective for repeated ruptured IIAs.

Discovery of ex situ individuals of Andrias sligoi, an extremely endangered species and one of the largest amphibians worldwide.

The South China giant salamander, Andrias sligoi, is one of the largest extant amphibian species worldwide. It was recently distinguished from another Chinese species, the Chinese giant salamander, Andrias davidianus, which is considered Critically Endangered according to the International Union for Conservation of Nature (IUCN) Red List. It appears too late to save this extremely rare and large amphibian in situ. Another extant species of the same genus, Andrias japonicus, inhabits Japan. However, the introduction of Chinese giant salamanders into some areas of Japan has resulted in hybridization between the Japanese and Chinese species. During our genetic screening of giant salamanders in Japan, we unexpectedly discovered four individuals of the South China giant salamander: two were adult males in captivity, and one had recently died. The last individual was a preserved specimen. In this study, we report these extremely rare individuals of A. sligoi in Japan and discuss the taxonomic and conservational implications of these introduced individuals.

Senescence-associated secretory phenotypes in mesenchymal cells contribute to cytotoxic immune response in oral lichen planus.

Oral lichen planus is a chronic inflammatory condition that adversely affects the oral mucosa; however, its etiology remains elusive. Consequently, therapeutic interventions for oral lichen planus are limited to symptomatic management. This study provides evidence of the accumulation of senescent mesenchymal cells, CD8 + T cells, and natural killer cells in patients with oral lichen planus. We profiled the patients' tissues using the National Center for Biotechnology Information Gene Expression Omnibus database and found that senescence-related genes were upregulated in these tissues by gene set enrichment analysis. Immunohistochemical analysis showed increased senescent mesenchymal cells in the subepithelial layer of patients with oral lichen planus. Single-cell RNA-seq data retrieved from the Gene Expression Omnibus database of patients with oral lichen planus revealed that mesenchymal cells were marked by the upregulation of senescence-related genes. Cell-cell communication analysis using CellChat showed that senescent mesenchymal cells significantly influenced CD8 + T cells and natural killer cells via CXCL12-CXCR4 signaling, which is known to activate and recruit CD8 + T cells and NK cells. Finally, in vitro assays demonstrated that the secretion of senescence-associated factors from mesenchymal cells stimulated the activation of T cells and natural killer cells and promoted epithelial cell senescence and cytotoxicity. These findings suggest that the accumulation of mesenchymal cells with senescence-associated secretory phenotype may be a key driver of oral lichen planus pathogenesis.

Proposal for a Simple Equation for Limb Muscle Weight Calculation.

BACKGROUND Although body mass index (BMI) is currently being utilized frequently as an indicator of obesity, it provides little information concerning body composition; key components such as fat and muscle cannot be differentiated. It is especially non-sensitive in identifying muscle mass, which can be challenging to examine without the use of radiologic methods. We sought to identify whether biometric values such as upper arm subcutaneous fat thickness/circumference could provide an adequate indicator of muscle mass. MATERIAL AND METHODS Patients admitted to our clinic for various causes were retrospectively studied in 95 consecutive cases. Physical parameters including upper arm subcutaneous fat thickness, upper arm circumference, weight, and height were measured. Then, values such as limb muscle weight (LMWDXA) and total fat weight (FWDXA) were obtained from dual-energy X-ray absorptiometry. Pearson's correlation coefficients were calculated and linear regression analysis was conducted. RESULTS Neither upper arm subcutaneous fat thickness nor upper arm circumference was correlated with LMWDXA. FWDXA also showed a correlation with BMI (r=0.823, P<0.001). LMWDXA also significantly correlated with measured body weight (BWm)-BMI (r=0.719, P<0.001). CONCLUSIONS From our analytic data we propose an equation for calculating muscle mass, designated the Simple Muscle Weight (SMW): SMW=289.2×(BWm-BMI)+3631. SMW calculation has potential for use as an easy and simple first-line diagnostic tool to identify diminished muscle mass.

Fisetin reduces the senescent tubular epithelial cell burden and also inhibits proliferative fibroblasts in murine lupus nephritis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease characterized by the involvement of multiple organs. Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in SLE patients. Hence, designing effective drugs is pivotal for treating individuals with LN. Fisetin plays a senolytic role by specifically eliminating senescent cells, inhibiting cell proliferation, and exerting anti-inflammatory, anti-oxidant, and anti-tumorigenic effects. However, limited research has been conducted on the utility and therapeutic mechanisms of fisetin in chronic inflammation. Similarly, whether the effects of fisetin depend on cell type remains unclear. In this study, we found that LN-prone MRL/lpr mice demonstrated accumulation of Ki-67-positive myofibroblasts and p15INK4B-positive senescent tubular epithelial cells (TECs) that highly expressed transforming growth factor ß (TGF-ß). TGF-ß stimulation induced senescence of NRK-52E renal TECs and proliferation of NRK-49F renal fibroblasts, suggesting that TGF-ß promotes senescence and proliferation in a cell type-dependent manner, which is inhibited by fisetin treatment in vitro. Furthermore, fisetin treatment in vivo reduced the number of senescent TECs and myofibroblasts, which attenuated kidney fibrosis, reduced senescence-associated secretory phenotype (SASP) expression, and increased TEC proliferation. These data suggest that the effects of fisetin vary depending on the cell type and may have therapeutic effects in complex and diverse LN pathologies.

Balloon Pulmonary Angioplasty for Takayasu Arteritis and Peripheral Pulmonary Artery Stenosis Mimicking Chronic Thromboembolic Pulmonary Hypertension.

Balloon pulmonary angioplasty (BPA) has been reported to be effective and safe to an acceptable level in patients with distal-type, inoperable chronic thromboembolic pulmonary hypertension (CTEPH), resulting in improved long-term survival. However, evidenced treatment options and strategy including medical therapy of antithrombotic therapy, glucocorticoids, immunosuppressants, and pulmonary hypertension (PH)-specific therapies are scarce in patients with significant PH and right heart failure associated with Takayasu arteritis and peripheral pulmonary artery stenosis, both of which mimic CTEPH. Moreover, there has been still concern on safety and lack of established methodology in performing BPA for these conditions. In this report, we would like to review recent publications including several case reports and discuss the efficacy, safety, and suitable methods of BPA in this population.

Intrathecal Injection of Mesenchymal Stromal Cell Cultured on 3D Fiber Ameliorates Multiple Organ Damage in Murine Lupus.

Up to 60% of patients with systemic lupus erythematosus (SLE) experience autonomic symptom. Sympathetic nervous system damage can cause dysfunction of the bone marrow that activates inflammatory cells, potentially causing multiple organ damage. We hypothesized that sympathetic nervous system damage would induce bone marrow dysfunction with multiple organ damage in SLE, and that multiple organ damage could be improved by therapy targeting the nervous system. Here, we showed that damage to autonomic nerves and Schwann cells occurred in the bone marrow and central nervous system of SLE model mice. A neurotoxic drug increased mortality and induced severe neuropathy and multiple organ damage, while a neuroprotective drug prevented multiple organ damage. The administration of bone marrow-derived mesenchymal stromal cells (BMSCs) cultured on a 3-dimensional fiber scaffold improved bone marrow neuropathy, skin lesions, kidney function, and mortality. Our results reveal that bone marrow neuropathy influence multiple organ damage associated with SLE, and improvement of bone marrow neuropathy by intrathecal injection of BMSC may be a target for SLE multiple-organ damage.

Altered regulation of mesenchymal cell senescence in adipose tissue promotes pathological changes associated with diabetic wound healing.

Pathologic diabetic wound healing is caused by sequential and progressive deterioration of hemostasis, inflammation, proliferation, and resolution/remodeling. Cellular senescence promotes wound healing; however, diabetic wounds exhibit low levels of senescent factors and accumulate senescent cells, which impair the healing process. Here we show that the number of p15INK4B + PDGFRα + senescent mesenchymal cells in adipose tissue increases transiently during early phases of wound healing in both non-diabetic mice and humans. Transplantation of adipose tissue from diabetic mice into non-diabetic mice results in impaired wound healing and an altered cellular senescence-associated secretory phenotype (SASP), suggesting that insufficient induction of adipose tissue senescence after injury is a pathological mechanism of diabetic wound healing. These results provide insight into how regulation of senescence in adipose tissue contributes to wound healing and could constitute a basis for developing therapeutic treatment for wound healing impairment in diabetes.

Predictors of recurrence of atrial tachyarrhythmias after pulmonary vein isolation by functional and structural mapping of nonparoxysmal atrial fibrillation.

BACKGROUND: This study aimed to evaluate the predictors of recurrence of atrial tachyarrhythmias by structural and functional mapping: voltage, dominant frequency (DF), and rotor mapping after a pulmonary vein isolation (PVI) in nonparoxysmal atrial fibrillation (AF) patients. METHODS: A total of 66 nonparoxysmal AF patients were prospectively investigated. After the PVI, an online real-time phase mapping system was used to detect the location of rotors with critical nonpassively activated ratios (%NPs) of ≧50% in each left atrial (LA) segment, and high-DFs of ≧7 Hz were simultaneously mapped. After restoring sinus rhythm, low-voltage areas (LVAs < 0.5 mV) were mapped using the Advisor HD grid catheter (HDG). RESULTS: Sixty-four of 66 (97%) AF patients had minimum to mild LVAs regardless of an enlarged LAD and LA volume (45 ± 6.0 mm and 141 ± 29 ml). There were no significant differences in the max and mean DF values and %NPs between the patients with and without recurrent atrial tachyarrhythmias. However, there was a significant difference in the LVA/LA surface area between the patients with and without recurrent atrial tachyarrhythmias (p = .004). Atrial tachyarrhythmia freedom was significantly greater in those with LVAs of ≤3.3% than in those >3.3% after one procedure over 11.6 ± 0.8 months of follow-up (77.1% vs. 33.3%, p < .001). In a multivariate analysis, the LVA/LA surface area after the PVI (HR 1.079; CI, 1.025-1.135, p = .003) was an independent predictor of AF recurrence. CONCLUSIONS: The predictor of atrial tachyarrhythmia recurrence after the PVI was LVAs rather than DFs and rotors in nonparoxysmal AF patients.

A Case of an Early Pregnant Woman with Congenital Protein S Deficiency Who Underwent Mechanical Thrombectomy.

Objective: Large vessel occlusion (LVO) stroke during pregnancy is rare but a life-threatening issue for the mother and fetus. We report a rare case of a pregnant woman with congenital protein S deficiency who underwent mechanical thrombectomy. Case Presentation: A 35-year-old woman presented with right hemiplegia and aphasia. The National Institutes of Health Stroke Scale was 23 and MRI revealed acute infarction on the left hemisphere. MRA showed disruption of the left middle cerebral artery. Mechanical thrombectomy was performed following intravenous thrombolysis, and then complete recanalization was achieved. The reduction in protein S activity due to pregnancy was suspected to have affected LVO. Subsequently, the patient was diagnosed with congenital protein S deficiency and recovered to modified Rankin scale 2 at 3 months after the onset. Conclusion: Aggravation of congenital protein S deficiency due to pregnancy led to the onset of LVO. The patient showed a good outcome after mechanical thrombectomy.

Accumulation of Senescent Neural Cells in Murine Lupus With Depression-Like Behavior.

Neuropsychiatric manifestations targeting the central, peripheral, and autonomic nervous system are common in systemic lupus erythematosus (SLE); collectively, these symptoms are termed neuropsychiatric SLE (NPSLE). Among a wide variety of neuropsychiatric symptoms, depression is observed in about 24-39% of SLE patients. Several cytokines and chemokines have been identified as biomarkers or therapeutic targets of NPSLE; in particular, the levels of type 1 interferons, TNFs, and IL-6 are elevated in SLE patient's cerebrospinal fluid (CSF), and these factors contribute to the pathology of depression. Here, we show that senescent neural cells accumulate in the hippocampal cornu ammonis 3 (CA3) region in MRL/lpr SLE model mice with depressive behavior. Furthermore, oral administration of fisetin, a senolytic drug, reduced the number of senescent neural cells and reduced depressive behavior in the MRL/lpr mice. In addition, transcription of several senescence and senescence-associated secretory phenotype (SASP) factors in the hippocampal region also decreased after fisetin treatment in the MRL/lpr mice. These results indicate that the accumulation of senescent neural cells in the hippocampus plays a role in NPSLE pathogenesis, and therapies targeting senescent cells may represent a candidate approach to treat NPSLE.

A Case of Spinal Ependymoma Developed in the Extramedullary Location: A Case Report and Literature Review.

Intradural extramedullary (IDEM) ependymoma except for tumors originated from the filum terminale or conus medullaris is rare. The present study showed a case of IDEM ependymoma. A 16-year-old boy was referred to our hospital with a complaint of right hypochondriac pain and motor weakness in his right leg. MRI revealed a solitary intradural tumor at Th5-8 level with syringomyelia at Th2-4 level. Microscopic total tumor resection was performed with right hemi-laminectomy of Th4-9. Histological diagnosis was ependymoma (WHO grade 2). Although his leg weakness was worsened transiently, he showed improvement in leg weakness being able to go up and down the stairs 1 month after the surgery. There was no tumor recurrence until now, 7 years after the surgery, without any adjunctive therapies. A total of 44 cases of IDEM ependymoma had been reported in the past literatures. They are thought to arise from ependymal cells which remained during the process of neural tube closure. Like intramedullary ependymomas, most of the IDEM ependymomas have clear border to surrounding tissue and often removed completely. However, a small number of recurrences and malignant transformations had been reported after complete resections despite benign histological features tumors. In the case of totally resected low grade IDEM ependymoma, it is thought to be reasonable to perform long-term periodical radiographic follow-up without postoperative adjunctive therapy.

Ruptured Blister-like Aneurysm Arising From the Proximal Posterior Cerebral Artery.

BACKGROUND: Blister-like aneurysms (BLAs) arise mostly at the supraclinoid internal carotid artery. We report a rare case of ruptured BLA arising at the P1 segment of the posterior cerebral artery (PCA). CASE DESCRIPTION: A 34-year-old woman presented with disturbance of consciousness. Computed tomography (CT) of the head showed diffuse subarachnoid hemorrhage (SAH). A tiny bulge on the right PCA P1 segment was observed on initial CT angiography. The lesion enlarged little-by-little, with re-rupture occurring 10 days after initial hemorrhage. We diagnosed BLA arising at the P1 segment, and performed emergent endovascular parent artery occlusion (PAO) of the P1 segment. No infarction was observed in the territory of the PCA postoperatively. CONCLUSIONS: Proximal PCA is a rare but possible location for BLA. When the cause of bleeding SAH cannot be identified, repeated radiologic assessments including posterior circulation should be performed. If perforators of the unaffected site supply the thalamus and midbrain bilaterally and an ipsilateral posterior communicating artery exists, PAO of P1 seems feasible as a treatment. Elective intervention is not recommended because of the characteristics of ruptured BLAs.

Neurosarcoidosis Presenting with Obstructive Hydrocephalus Successfully Treated with Endoscopic Third Ventriculostomy.

A 58-year-old Japanese woman complained of unstable gait and dizziness lasting for a month. She had been diagnosed histologically with pulmonary and cutaneous sarcoidosis and attended outpatient clinics for routine checkups. Head computed tomography and magnetic resonance imaging (MRI) indicated obstructive hydrocephalus caused by a contrast-enhanced lesion in the cerebral aqueduct. The patient underwent endoscopic third ventriculostomy and a biopsy of the lesion, leading to the diagnosis of neurosarcoidosis. This was a rare case of neurosarcoidosis presenting with obstructive hydrocephalus that was treated with endoscopic third ventriculostomy and diagnosed histologically via an intraoperative biopsy.

Cervical Open-Door Laminoplasty by Hydroxyapatite Implant Insertion Without Suturing.

OBJECTIVE: To assess the efficacy of cervical open-door laminoplasty by hydroxyapatite implant insertion between the lamina and the lateral mass without suturing. METHODS: All patients who underwent cervical open-door laminoplasty with C2/C7 undermining and insertion of hydroxyapatite implants from C3 to C6 were retrospectively evaluated for surgical time and neurological outcomes according to the Japanese Orthopaedic Association (JOA) score. To assess the alignment of the cervical spine and postoperative cervical pain, the C2-7 angle and a visual analogue scale score were used, respectively. RESULTS: The population consisted of 102 women and 222 men ranging in age from 32 to 90 years. The average surgical time was 86 minutes. Fourteen of 1,296 hydroxyapatite implants were kept in place with sutures due to a weak restoration force of the hinge during surgery. No hydroxyapatite implant dislocation was detected on cervical computed tomography at 1 year after surgery. The average JOA score was 10.2±2.5 before surgery and 14.6±2.8 at 1 year after surgery. The average recovery rate was 61.8%. The average C2-7 angle at the neutral position was 7.1°±6.2° before surgery and 6.5°±6.3° at 1 year after surgery. CONCLUSION: This method enabled us to achieve minimal exposure of the lateral mass, prevention of lateral mass injury and dural injury, and a shorter surgical time while maintaining acceptable surgical outcomes. The idea that firm suture fixation is needed to prevent spacer deviation during cervical open-door laminoplasty may need to be revisited.

Short-Term Results of Carotid Endarterectomy and Stenting After the Introduction of Carotid Magnetic Resonance Imaging: A Single-Institution Retrospective Study.

OBJECTIVE: Although carotid artery stenting (CAS) has been gaining popularity as an alternative to carotid endarterectomy (CEA), perioperative stroke rate following contemporary CAS remains significantly higher than stroke rate after CEA. The purpose of this study was to assess perioperative (within 30 days) therapeutic results in patients with carotid stenosis (CS) after introduction of preoperative carotid magnetic resonance imaging plaque evaluation in a single center performing both CEA and CAS. METHODS: Based on prospectively collected data for patients with CS who were scheduled for carotid revascularization, retrospective analysis was conducted of 295 consecutive patients with CS. An intervention was selected after consideration of periprocedural risks for both CEA and CAS. Concerning risk factors for CAS, results of magnetic resonance imaging plaque evaluation were emphasized with a view toward reducing embolic complications. RESULTS: CAS was performed in 114 patients, and CEA was performed in 181 patients. Comparing baseline characteristics of the 295 patients, age, T1 signal intensity of plaque, symptomatic CS, urgent intervention, and diabetes mellitus differed significantly between CAS and CEA groups. Among patients who underwent CAS, new hyperintense lesions on diffusion-weighted imaging were confirmed in 47 patients. New hyperintense lesions on diffusion-weighted imaging were recognized in 21.4% of patients who underwent CEA (n = 39), significantly less frequent than in patients who underwent CAS. CONCLUSIONS: The overall short-term outcome of CEA and CAS is acceptable. Preoperative carotid magnetic resonance imaging evaluation of plaque might contribute to low rates of ischemic complications in CAS.

Reduced cerebrovascular reserve is associated with an increased risk of postoperative ischemic lesions during carotid artery stenting.

BACKGROUND: Reduced cerebrovascular reserve (CVR) is associated with increased risk of ischemic events in carotid steno-occlusive diseases. OBJECTIVE: To determine whether pretreatment CVR can predict postoperative ischemic lesions after carotid artery stenting (CAS) by retrospective analysis. METHODS: We retrospectively reviewed the medical records of 46 patients (42 men; mean age 74.2±8.3 years) who underwent CAS and preprocedural cerebral blood flow measurement by quantitative single-photon emission CT. Ischemic lesions were evaluated by diffusion-weighted image (DWI) within 72 h after the intervention. We also evaluated plaque characteristics using black-blood MR plaque imaging. RESULTS: New ipsilateral DWI-positive lesions were found in 11 cases (23.9%). Patients were classified into two groups based on the presence or absence of new DWI-positive lesions, and no significant differences in characteristics were found between the DWI-positive and DWI-negative groups, except for age and CVR of the ipsilateral middle cerebral artery (MCA) territory. The DWI-positive group was significantly older than the DWI-negative group (79.7±4.1 vs 72.5±8.6 years; p=0.0085) and had lower average regional CVR (1.4±18.2% vs 22.4±25.8%; p=0.016). MR plaque imaging showed no significant difference in relative overall plaque MR signal intensity between the two groups (1.53±0.37 vs 1.34±0.26; p=0.113). In multivariate logistic regression analysis, lower CVR of the ipsilateral MCA territory (<11%) was the only independent risk factor for new ischemic lesions following CAS (OR=6.99; 95% CI 1.17 to 41.80; p=0.033). CONCLUSIONS: Impaired pretreatment CVR was associated with increased incidence of new infarction after CAS.