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Abstract Background The increasing prevalence of heated tobacco products (HTPs) has heightened concerns regarding their potential health risks. Previous studies have demonstrated the toxicity of cigarette smoke extract (CSE) from traditional tobacco’s mainstream smoke, even after the removal of nicotine and tar. Our study aimed to investigate the cytotoxicity of CSE derived from HTPs and traditional tobacco, with a particular focus on the role of reactive oxygen species (ROS) and intracellular Ca2+. Methods A human oral squamous cell carcinoma (OSCC) cell line, HSC-3 was utilized. To prepare CSE, aerosols from HTPs (IQOS) and traditional tobacco products (1R6F reference cigarette) were collected into cell culture media. A cell viability assay, apoptosis assay, western blotting, and Fluo-4 assay were conducted. Changes in ROS levels were measured using electron spin resonance spectroscopy and the high-sensitivity 2ʹ,7ʹ-dichlorofluorescein diacetate assay. We performed a knockdown of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) by shRNA lentivirus in OSCC cells. Results CSE from both HTPs and traditional tobacco exhibited cytotoxic effects in OSCC cells. Exposure to CSE from both sources led to an increase in intracellular Ca2+ concentration and induced p38 phosphorylation. Additionally, these extracts prompted cell apoptosis and heightened ROS levels. N-acetylcysteine (NAC) mitigated the cytotoxic effects and p38 phosphorylation. Furthermore, the knockdown of CaMKK2 in HSC-3 cells reduced cytotoxicity, ROS production, and p38 phosphorylation in response to CSE. Conclusion Our findings suggest that the CSE from both HTPs and traditional tobacco induce cytotoxicity. This toxicity is mediated by ROS, which are regulated through Ca2+ signaling and CaMKK2 pathways. Graphical Abstract

Aortic leiomyosarcoma, a rare and elusive malignancy, presents diagnostic and therapeutic dilemmas due to its nonspecific symptoms and aggressive course. We report a unique case where the incidental discovery of arterial leiomyosarcoma occurred during acute cerebral infarction management. A previously healthy 58-year-old woman, initially presenting with severe neurological deficits indicative of acute ischemic stroke, underwent prompt recanalization therapy that resulted in successful restoration. Unexpectedly, a histopathological examination of the extracted thrombus revealed arterial leiomyosarcoma. The diagnostic process involved immunohistochemistry and contrast-enhanced computed tomography, confirming the presence of leiomyosarcoma originating from the ascending aorta. Given the patient's severe disability, a palliative care approach was chosen to prioritize comfort and quality of life. This case underscores the diagnostic potential of acute recanalization therapy for functional recovery as well as histopathological examination, shedding light on rare diseases. Further case accumulation is essential to refine treatment strategies and improve prognostic outcomes for vascular sarcomas.

Post-traumatic headache is a common secondary headache disorder caused by head or neck trauma. However, the etiology and management have not been established. Here, we present a unique case of steroid-responsive acute post-traumatic headache with neuroinflammation following a mild head injury.A 19-year-old female soccer player experienced persistent headache, vomiting, and low-grade fever after sustaining a mild sports-related head injury. Subsequent cerebrospinal fluid (CSF) examination and contrast-enhanced magnetic resonance imaging (MRI) revealed leptomeningeal contrast enhancement, elevated intracranial pressure, and an increased CSF cell count. Notably, the patient tested negative for viral, fungal, tumor, and autoimmune markers, thus a diagnosis of acute post-traumatic headache with neuroinflammation was determined. Treatment with dexamethasone (8 mg/day) resulted in rapid symptom relief, enabling the patient to return to sports without symptom recurrence.This case highlights the importance of considering post-traumatic headache with neuroinflammation in patients with atypical post-head injury symptoms. Although her condition shared clinical similarities with concussions, the presence of fever accompanied with specific MRI and CSF findings offered critical diagnostic differentiators. Additionally, our report highlights the potential underdiagnosis of steroid-responsive neuroinflammation following head injury and the necessity for active differential diagnosis.

Common carotid artery (CCA) occlusion (CCAO) is a rare cause of ischemic stroke and bypass surgery is the common treatment approach. However, safer alternatives should be developed to treat CCAO. A 68-year-old male was diagnosed with left-sided CCAO with decreased left visual acuity due to neck radiation therapy for laryngeal cancer. Recanalization therapy using a pull-through technique was initiated because cerebral blood flow progressively decreased during the follow-up period. First, after a short sheath was inserted into the CCA, the occluded CCA was retrogradely penetrated through the sheath. Second, a micro-guidewire was guided to the aorta from the femoral sheath where it was caught using a snare wire guided from the cervical sheath. Subsequently, the micro-guidewire was gently pulled out from the cervical sheath, penetrated the occluded lesion, and was secured to the femoral and cervical sheaths. Finally, the occluded lesion was dilated using a balloon, and the stent was placed. Five days postprocedure, the patient was discharged uneventfully and exhibited improved left visual acuity. In terms of reliable penetration of obstructive lesions and reduction of embolic and hemorrhagic complications, combined endovascular antegrade and direct retrograde carotid artery stenting is a versatile and minimally invasive treatment option for CCAO.

Abstract Background Subarachnoid hemorrhage and thyroid storm are similar in their clinical symptomatology, and diagnosis of these conditions, when they occur simultaneously, is difficult. Here, we report a rare case of concurrent subarachnoid hemorrhage and thyroid storm we encountered at our hospital. Case presentation The patient was a 52-year-old woman. While bathing at home, the patient experienced a sudden disturbance of consciousness and was brought to our hospital. The main physical findings upon admittance were Glasgow Coma Scale score of E1V2M4, elevated blood pressure (208/145 mmHg), and tachycardia with atrial fibrillation (180 bpm) along with body temperature of 36.1 °C. Brain computed tomography revealed subarachnoid hemorrhage associated with a ruptured aneurysm of the posterior communicating artery branching from the left internal carotid artery, and aneurysm clipping was performed. Blood tests upon admission revealed high levels of free T3 and free T4 and low levels of thyroid-stimulating hormone. Upon determining that the patient had hyperthyroidism, thiamazole was administered. However, due to continuous impaired consciousness, fever, and persistence of tachycardia, the patient was diagnosed with thyroid storm. Oral potassium iodide and hydrocortisone were added to the treatment. The treatment was successful as the patient’s symptoms improved, and she became lucid. In this case, we believe that in the presence of untreated hyperthyroidism, the onset of subarachnoid hemorrhage induced thyroid storm. Tachycardia of 130 bpm or higher, which is the diagnostic criterion for thyroid storm, rarely occurs with subarachnoid hemorrhage. Therefore, we believe it is an important factor for recognizing the presence of the thyroid storm. In this case, clipping surgery was prioritized which resulted in a favorable outcome. However, it is possible that invasive surgery may have exacerbated thyroid storm, suggesting that treatment should be tailored as per patient’s condition. Conclusion If a pulse rate of 130 bpm or higher is observed alongside subarachnoid hemorrhage, we recommend considering the possibility of concomitant thyroid storm and testing for thyroid hormone. If concomitant thyroid storm is present, we believe that a treatment plan tailored to the patient’s condition is critical, and early diagnosis will lead to a favorable outcome for the patient.

Background: Risk-benefit analysis results for the treatment of unruptured aneurysms smaller than 5 mm are controversial. This study aimed to identify the outcomes and complication associated with treating such unruptured aneurysms. Methods: This was a retrospective study of 165 consecutive patients who underwent endovascular procedures for unruptured cerebral aneurysms of a maximum diameter 5 mm between January 2018 and March 2021. Patient background, aneurysm characteristics, adjuvant technique, volume embolization rate (VER), symptomatic complications, and modified Rankin Scale (mRS) scores were examined. Results: Sixty patients with sufficient data were included in the study. The mean age was 62.1 ± 14.6 years, and the median follow-up period was 12 months. The mean maximum diameter was 4.16 ± 0.63 mm, the neck diameter was 2.73 ± 0.82 mm, and 90% of patients had anterior circulation. Complete occlusion was achieved in 34 cases (57.6%). Although there were no intraoperative ruptures, complications were observed in four patients (6.7%), and one patient (1.7%) had worsened mRS score. Only one patient (1.7%) required retreatment. The first coil VER was independently associated with complete occlusion after endovascular treatment. Univariate analysis of complications showed an association between hypertension, hyperlipidaemia, and the estimated glomerular filtration rate. Conclusions: No patient experienced mRS score deterioration, and only one patient developed permanent disability due to ischemic complications; hence, we could safely treat small unruptured aneurysms. Complications are not related to procedural factors such as coiling adjuvant technique. However, lifestyle-related diseases are related to complications, and we suggest that physicians should remain vigilant of the indication for coiling when treating patients with underlying diseases.

Introduction: Vertebral artery injury (VAI) due to blunt cervical spine injury (BCSI) can cause severe cerebral infarction. This study aimed to evaluate the risks of cerebral infarction and to develop a brain screening algorithm in patients with BCSI. Methods: We examined the characteristics of 37 consecutive patients diagnosed with BCSI at our institute between January 2017 and April 2021 and retrospectively analyzed the risk factors for post-trauma cerebral infarction, such as patient background characteristics, fracture side and level, vertebral artery (VA) status, details of treatment, and complications. Results: A total of 12 patients (32.4%) had VAI, of whom six were treated with intravascular coil embolization to prevent cerebral infarction after cervical spine surgery. Of the five patients (13.5%) with cerebral infarction, four had VAI and one had intact VAs but with a fracture of the intervertebral foramen on the dominant side of the VA (illustrative case). Only the presence of VAI showed a significant difference in the risk of cerebral infarction onset (p = 0.015). Coil embolization did not increase the risk of postoperative cerebral infarction (p = 0.12). Conclusion: VAI was the only risk factor for the development of cerebral infarction in patients with BCSI, suggesting that head magnetic resonance imaging (MRI) screening is recommended for those with VAI. In patients without VAI, vertebral fractures on the dominant side of the VA might be a risk for cerebral infarction, indicating that head MRI screening should also be considered in these patients.

This study investigated the effect of Mahjong, which is a table game played by three or four players and involves intellectual activity, on the intelligence quotient (IQ) of children. The participants were children between the age of 6 and 15 years, and their IQ was assessed immediately after enrolling in children's Mahjong classes and 1 year after the enrollment using the Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV). Twenty children were included in the analysis. Their mean age at the time of the initial evaluation was 9 years and 6 months. In addition, we conducted a 1-year post-examination. The change in the IQ of this group was compared to that of a historical control group with a similar age range and test–retest interval. The mean overall full-scale IQ of the 20 children during the initial and post-1-year examinations was 106.05 and 113.75, respectively, and showed a statistically significant increase (p < 0.01). Based on the subscale index, the verbal comprehension index (VCI) and processing speed index (PSI) scores both showed a statistically significant increase from 100.6 to 106.75 and from 108.05 to 119.05 (p < 0.01), respectively. The PSI of the children included in the analysis showed a statistically significant increase compared to the historical control group. This study suggests that children who participate in Mahjong classes during their childhood have increased PSI scores of WISC-IV.

Iron-salen, i.e., μ-oxo-N,N′-bis(salicylidene)ethylenediamine iron (Fe(Salen)) was a recently identified as a new anti-cancer compound with intrinsic magnetic properties. Chelation therapy has been widely used in management of metallic poisoning, because an administration of agents that bind metals can prevent potential lethal effects of particular metal. In this study, we confirmed the therapeutic effect of deferoxamine mesylate (DFO) chelation against Fe(Salen) as part of the chelator antidote efficacy. DFO administration resulted in reduced cytotoxicity and ROS generation by Fe(Salen) in cancer cells. DFO (25 mg/kg) reduced the onset of Fe(Salen) (25 mg/kg)-induced acute liver and renal dysfunction. DFO (300 mg/kg) improves survival rate after systematic injection of a fatal dose of Fe(Salen) (200 mg/kg) in mice. DFO enables the use of higher Fe(Salen) doses to treat progressive states of cancer, and it also appears to decrease the acute side effects of Fe(Salen). This makes DFO a potential antidote candidate for Fe(Salen)-based cancer treatments, and this novel strategy could be widely used in minimally-invasive clinical settings.

Abstract Shortage of autologous blood vessel sources and disadvantages of synthetic grafts have increased interest in the development of tissue-engineered vascular grafts. However, tunica media, which comprises layered elastic laminae, largely determines arterial elasticity, and is difficult to synthesize. Here, we describe a method for fabrication of arterial grafts with elastic layer structure from cultured human vascular SMCs by periodic exposure to extremely high hydrostatic pressure (HP) during repeated cell seeding. Repeated slow cycles (0.002 Hz) between 110 and 180 kPa increased stress-fiber polymerization and fibronectin fibrillogenesis on SMCs, which is required for elastic fiber formation. To fabricate arterial grafts, seeding of rat vascular SMCs and exposure to the periodic HP were repeated alternatively ten times. The obtained medial grafts were highly elastic and tensile rupture strength was 1451 ± 159 mmHg, in which elastic fibers were abundantly formed. The patch medial grafts were sutured at the rat aorta and found to be completely patent and endothelialized after 2.5 months, although tubular medial constructs implanted in rats as interpositional aortic grafts withstood arterial blood pressure only in early acute phase. This novel organized self-assembly method would enable mass production of scaffold-free arterial grafts in vitro and have potential therapeutic applications for cardiovascular diseases.

We consider the essence of human intelligence to be the ability to mentally (internally) construct a world in the form of stories through interactions with external environments. Understanding the principles of this mechanism is vital for realizing a human-like and autonomous artificial intelligence, but there are extremely complex problems involved. From this perspective, we propose a conceptual-level theory for the computational modeling of generative narrative cognition. Our basic idea can be described as follows: stories are representational elements forming an agent’s mental world and are also living objects that have the power of self-organization. In this study, we develop this idea by discussing the complexities of the internal structure of a story and the organizational structure of a mental world. In particular, we classify the principles of the self-organization of a mental world into five types of generative actions, i.e., connective, hierarchical, contextual, gathering, and adaptive. An integrative cognition is explained with these generative actions in the form of a distributed multiagent system of stories.

Objective: Carotid artery stenting embolic protection devices offer various options, among which distal filter protection is the simplest and easiest to handle. However, compared to balloon protection systems, distal filter protection has more embolic complications. Therefore, we explored the risk factors of distal filter protection, intending to achieve a safer carotid artery stenting. This retrospective study was conducted to identify prognostic factors following carotid artery stenting with only distal filter protection from July 2010 to June 2021. Methods: Information on patient background, procedures and devices, and complications was collected using medical records. The data pertaining to 187 patients were analyzed after excluding the data of patients in whom other protection devices (8 cases) were used. We used FilterWire EZ as the first choice for embolic protection device and SpiderFX when the patients had difficult-to-cross lesions. Results: The patients' mean age was 71.9 ± 6.9 years, and 72 (38.5%) were symptomatic. Symptomatic (odds ratio: 2.02, p = 0.035) and difficult-to-cross lesions (odds ratio: 3.63, p = 0.0013) were factors independently associated with symptomatic complications. Conclusion: This retrospective single-center study established independent prognostic factors for carotid artery stenting with distal filter protection. For patients with symptomatic lesions and severe stenosis or bends that are difficult to pass through, it is necessary to be careful when performing carotid artery stenting with distal filter protection. [ABSTRACT FROM AUTHOR]

Background Meningiomas are often embolized preoperatively to reduce intraoperative blood loss and facilitate tumor resection. However, the procedure is controversial and its effects have not yet been reported. We evaluated preoperative embolization for meningiomas and its effect on postoperative outcome and recurrence. Methods We retrospectively reviewed the medical records of 186 patients with WHO grade I meningiomas who underwent surgical treatment at our hospital between January 2010 and December 2020. We used propensity score matching to generate embolization and no-embolization groups (42 patients each) to examine embolization effects. Results Preoperative embolization was performed in 71 patients (38.2%). In the propensity-matched analysis, the embolization group showed favorable recurrence-free survival (RFS) (mean 49.4 vs 24.1 months; Wilcoxon p=0.049). The embolization group had significantly less intraoperative blood loss (178±203 mL vs 221±165 mL; p=0.009) and shorter operation time (5.6±2.0 hours vs 6.8±2.8 hours; p=0.036). There were no significant differences in Simpson grade IV resection (33.3% vs 28.6%; p=0.637) or overall perioperative complications (21.4% vs 11.9%; p=0.241). Tumor embolization prolonged RFS in a subanalysis of cases who experienced recurrence (n=39) among the overall cases before variable control (mean RFS 33.2 vs 16.0 months; log-rank p=0.003). Conclusions After controlling for variables, preoperative embolization for meningioma did not improve the Simpson grade or patient outcomes. However, it might have effects outside of surgical outcomes by prolonging RFS without increasing complications. [ABSTRACT FROM AUTHOR]