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Coronavirus disease 2019 (COVID-19) induces respiratory dysfunction as well as kidney injury. Although the kidney is considered a target organ of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and affected by the COVID-19-induced cytokine storm, the mechanisms of renal reaction in SARS-CoV-2 infection are unknown. In this study, a murine COVID-19 model was induced by nasal infection with mouse-adapted SARS-CoV-2 (MA10). MA10 infection induced body weight loss along with lung inflammation in mice 4 days after infection. Serum creatinine levels and the urinary albumin/creatinine ratio increased on day 4 after MA10 infection. Measurement of the urinary neutrophil gelatinase-associated lipocalin/creatinine ratio and hematoxylin and eosin staining revealed tubular damage in MA10-infected murine kidneys, indicating kidney injury in the murine COVID-19 model. Interferon (IFN)-γ and interleukin-6 upregulation in the sera of MA10-infected mice, along with the absence of MA10 in the kidneys, implied that the kidneys were affected by the MA10 infection-induced cytokine storm rather than by direct MA10 infection of the kidneys. RNA-sequencing analysis revealed that antiviral genes, such as the IFN/Janus kinase (JAK) pathway, were upregulated in MA10-infected kidneys. Upon administration of the JAK inhibitor baricitinib on days 1-3 after MA10 infection, an antiviral pathway was suppressed, and MA10 was detected more frequently in the kidneys. Notably, JAK inhibition upregulated the hypoxia response and exaggerated kidney injury. These results suggest that endogenous antiviral activity protects against SARS-CoV-2-induced kidney injury in the early phase of infection, providing valuable insights into the pathogenesis of COVID-19-associated nephropathy.NEW & NOTEWORTHY Patients frequently present with acute kidney injury or abnormal urinary findings after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we investigated how the kidneys respond during SARS-CoV-2 infection using a murine coronavirus disease 2019 (COVID-19) model and showed that Janus kinase-mediated endogenous antiviral activity protects against kidney injury in the early phase of SARS-CoV-2 infection. These findings provide valuable insights into the renal pathophysiology of COVID-19.
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COVID-19 , Inhibidores de las Cinasas Janus , Purinas , Pirazoles , SARS-CoV-2 , Sulfonamidas , Animales , COVID-19/complicaciones , Inhibidores de las Cinasas Janus/farmacología , Inhibidores de las Cinasas Janus/uso terapéutico , Sulfonamidas/farmacología , Ratones , Purinas/farmacología , Pirazoles/farmacología , Modelos Animales de Enfermedad , Lesión Renal Aguda/virología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/metabolismo , Azetidinas/farmacología , Azetidinas/uso terapéutico , Quinasas Janus/metabolismo , Quinasas Janus/antagonistas & inhibidores , Riñón/patología , Riñón/virología , Riñón/metabolismo , Riñón/efectos de los fármacos , Tratamiento Farmacológico de COVID-19 , Antivirales/farmacología , Antivirales/uso terapéutico , Masculino , Ratones Endogámicos C57BLRESUMEN
The majority of low-grade isocitrate dehydrogenase-mutant (IDHmt) gliomas undergo malignant progression (MP), but their underlying mechanism remains unclear. IDHmt gliomas exhibit global DNA methylation, and our previous report suggested that MP could be partly attributed to passive demethylation caused by accelerated cell cycles. However, during MP, there is also active demethylation mediated by ten-eleven translocation, such as DNA hydroxymethylation. Hydroxymethylation is reported to potentially contribute to gene expression regulation, but its role in MP remains under investigation. Therefore, we conducted a comprehensive analysis of hydroxymethylation during MP of IDHmt astrocytoma. Five primary/malignantly progressed IDHmt astrocytoma pairs were analyzed with oxidative bisulfite and the Infinium EPIC methylation array, detecting 5-hydroxymethyl cytosine at over 850,000 locations for region-specific hydroxymethylation assessment. Notably, we observed significant sharing of hydroxymethylated genomic regions during MP across the samples. Hydroxymethylated CpGs were enriched in open sea and intergenic regions (p < 0.001), and genes undergoing hydroxymethylation were significantly associated with cancer-related signaling pathways. RNA sequencing data integration identified 91 genes with significant positive/negative hydroxymethylation-expression correlations. Functional analysis suggested that positively correlated genes are involved in cell-cycle promotion, while negatively correlated ones are associated with antineoplastic functions. Analyses of The Cancer Genome Atlas clinical data on glioma were in line with these findings. Motif-enrichment analysis suggested the potential involvement of the transcription factor KLF4 in hydroxymethylation-based gene regulation. Our findings shed light on the significance of region-specific DNA hydroxymethylation in glioma MP and suggest its potential role in cancer-related gene expression and IDHmt glioma malignancy.
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Neoplasias Encefálicas , Metilación de ADN , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Glioma , Isocitrato Deshidrogenasa , Factor 4 Similar a Kruppel , Mutación , Humanos , Isocitrato Deshidrogenasa/genética , Glioma/genética , Glioma/patología , Glioma/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Islas de CpG/genética , Femenino , Masculino , Astrocitoma/genética , Astrocitoma/patología , Astrocitoma/metabolismo , Persona de Mediana Edad , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , AdultoRESUMEN
Ependymomas encompass multiple clinically relevant tumor types based on localization and molecular profiles. Tumors of the methylation class "spinal ependymoma" (SP-EPN) represent the most common intramedullary neoplasms in children and adults. However, their developmental origin is ill-defined, molecular data are scarce, and the potential heterogeneity within SP-EPN remains unexplored. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and NF2 mutations, but neither types and frequency of these alterations nor their clinical relevance have been described in a large, epigenetically defined series. Transcriptomic (n = 72), epigenetic (n = 225), genetic (n = 134), and clinical data (n = 112) were integrated for a detailed molecular overview on SP-EPN. Additionally, we mapped SP-EPN transcriptomes to developmental atlases of the developing and adult spinal cord to uncover potential developmental origins of these tumors. The integration of transcriptomic ependymoma data with single-cell atlases of the spinal cord revealed that SP-EPN display the highest similarities to mature adult ependymal cells. Unsupervised hierarchical clustering of transcriptomic data together with integrated analysis of methylation profiles identified two molecular SP-EPN subtypes. Subtype A tumors primarily carried previously known germline or sporadic NF2 mutations together with 22q loss (bi-allelic NF2 loss), resulting in decreased NF2 expression. Furthermore, they more often presented as multilocular disease and demonstrated a significantly reduced progression-free survival as compared to SP-EP subtype B. In contrast, subtype B predominantly contained samples without NF2 mutation detected in sequencing together with 22q loss (monoallelic NF2 loss). These tumors showed regular NF2 expression but more extensive global copy number alterations. Based on integrated molecular profiling of a large multi-center cohort, we identified two distinct SP-EPN subtypes with important implications for genetic counseling, patient surveillance, and drug development priorities.
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Ependimoma , Neoplasias de la Médula Espinal , Adulto , Niño , Humanos , Transcriptoma , Perfilación de la Expresión Génica , Mutación , Epigénesis GenéticaRESUMEN
We present the photoreaction of newly prepared bis(6,6'-dimethyl-2,2'-bipyridine)(oxalato)rhodium(III) ([Rh(N^N)2(ox)]+) in CD3OD. Photoirradiation of this complex causes the dissociation of ox, followed by the formation of the unprecedented Rh(III) complex with Rh-H and Rh-C s bonds, [Rh(N^N)(C^N)(H)(CD3OD)]+ (C^N = [6,6'-dimethyl-2,2'-bipyridine]-3-yl-κC3,κN1'). This hydride formation and cyclometallation spontaneously proceed owing to the conflict between the steric hindrance arising from the methyl groups of N^N and the driving force for the structural change due to [Rh(N^N)2]+ formation. Although [Rh(N^N)(C^N)(H)(CD3OD)]+ is initially converted to [Rh(N^N)2]+ by photoirradiation, it is immediately regenerated by the rollover cyclometallation of the [Rh(N^N)2]+ complex. [Rh(N^N)(C^N)(H)(CD3OD)]+ undergoes H/D exchange for the H atoms in the Rh-H bond and at the 3, 3'-positions of the N^N ligand during the photoirradiation. DFT calculations predict with reasonable certainty the spontaneous structural change of [Rh(N^N)2]+ to [Rh(N^N)(C^N)(H)(CD3OD)]+ and the subsequent photodriven Rh-C bond rupture leading to the formation of [Rh(N^N)2]+ accompanied by H/D exchange reactions.
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AIMS: The study was to identify the genes involved in phage resistance and to develop an effective biocontrol method to improve the lytic activity of phages against foodborne pathogens. METHODS AND RESULTS: A total of 3,909 single gene-deletion mutants of Escherichia coli BW25113 from the Keio collection were individually screened for genes involved in phage resistance. Phage S127BCL3 isolated from chicken liver, infecting both E. coli BW25113 and O157: H7, was characterized and used for screening. The 10 gene-deletion mutants showed increased susceptibility to phage S127BCL3. Among them, priA gene-deletion mutant strain showed significant susceptibility to the phages S127BCL3 and T7. Furthermore, we investigated the substances that have been reported to inhibit the function of primosomal protein A (PriA) and were used to confirm increased phage susceptibility in E. coli BW25113 (Parent strain) and O157: H7. CONCLUSION: PriA inhibitors at a low concentration showed combined effects with phage against E. coli O157: H7 and delayed the regrowth rate of phage-resistant cells.
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Bacteriófagos , Escherichia coli O157 , Proteínas de Escherichia coli , Bacteriófagos/genética , Proteína Estafilocócica A , ADN Helicasas , Proteínas de Escherichia coli/genéticaRESUMEN
The number of patients with type 2 diabetes is increasing worldwide. The mechanisms leading to type 2 diabetes and its complications is being researched; however, the pathological mechanisms of diabetes in the small intestine remain unclear. Therefore, we examined these pathological mechanisms in the small intestine using a mouse model of type 2 diabetes (KK-Ay/TaJcl) aged 10 and 50 weeks. The results showed that diabetes worsened with age in the mice with type 2 diabetes. In these mice, advanced glycation end products (AGEs) in the small intestine and mast cell expression increased, whereas diamine oxidase (DAO) decreased; increased tumor necrosis factor (TNF)-α and histamine levels in the plasma and small intestine were also detected. Additionally, the expression of zonula occludens (ZO)-1 and Claudin1 and cell adhesion molecules in the small intestine reduced. These results exacerbated with age. These findings indicate that type 2 diabetes causes AGE/mast cell/histamine and TNF-α signal transmission in the small intestine and decreases small intestinal wall cell adhesion molecules cause TNF-α and histamine to flow into the body, worsening the diabetic condition. In addition, this sequence of events is suggested to be strengthened in aged mice with type 2 diabetes, thus exacerbating the disease. These findings of this study may facilitate the elucidation of the pathological mechanisms of type 2 diabetes and its associated complications.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Histamina/metabolismo , Intestino Delgado/metabolismo , Moléculas de Adhesión Celular , Productos Finales de Glicación Avanzada/metabolismoRESUMEN
5-Fluorouracil (5-FU), an effective chemotherapeutic agent for many solid tumors, has long been reported to cause pigmentation in patients treated intravenously, which occurs with increasing frequency of administration and decreases the QOL of the patients. Although melanin accumulation is thought to be the cause, the mechanism of pigmentation induced by 5-FU administration remains unclear, and there is no effective treatment for this problem. In this study, we investigated the mechanism of pigmentation induced by continuous 5-FU administration in 9-week-old male HRM-2 hairless mice for 8 weeks by focusing on the blood vessels for basic verification. In the auricular skin of 5-FU-administered mice, hyperpigmentation caused by melanin accumulation was observed macroscopically and by Fontana-Masson Staining. In addition, the expression of tyrosinase, melanin synthase, and blood vessel markers in the auricular skin was increased by 5-FU-administration in mice auricular skin. Other anticancer agents, cytarabine (Ara-C) and irinotecan (CPT-11), were also administered, and the differences between them and 5-FU were investigated; these changes were not observed in the auricles of these mice. These results suggest that tyrosinase is associated with 5-FU-induced melanin production and that an increase in blood vessels may be involved. Furthermore, pigmentation with melanin accumulation in the basal epidermal layer is a characteristic finding of 5-FU compared with Ara-C and CPT-11. In conclusion, this study indicates that 5-FU causes hyperpigmentation by melanin accumulation in a characteristic manner, including an increase in blood vessels.
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Hiperpigmentación , Melaninas , Humanos , Masculino , Animales , Ratones , Melaninas/metabolismo , Ratones Pelados , Fluorouracilo/efectos adversos , Irinotecán/uso terapéutico , Monofenol Monooxigenasa/metabolismo , Calidad de Vida , Pigmentación de la Piel , Hiperpigmentación/inducido químicamente , Citarabina/uso terapéuticoRESUMEN
INTRODUCTION: The characteristics of ski- and snowboard-related fatalities at Japanese ski resorts remain unknown. We aimed to analyze the characteristics of this in the current study. METHODS: Using the Ski Resort Injury Report data for the 13-y period between the 2011-12 and 2022-23 seasons, we described the characteristics of fatal accidents due to exogenous causes. RESULTS: Eighty-four subjects (48 skiers and 36 snowboarders) were analyzed. Males accounted for 73 cases of all 84 fatalities (86.9%), including 44 skiers (91.7%) and 29 snowboarders (80.6%). Skiers aged ≥50 y and snowboarders aged 20-35 y had the highest number of fatal accidents (32 and 18 cases, respectively). Regarding location, 26 fatal accidents occurred on slopes, and 58 occurred out of slopes (skiers, 11 and 37 cases; snowboarders, 15 and 21 cases, respectively). Among skiers, head and neck trauma accounted for the cause of death in 13 cases (27.1%) and asphyxiation in 11 cases (22.9%). Among snowboarders, head and neck trauma accounted for the cause of death in 14 cases (38.9%) and asphyxiation in 14 cases (38.9%). CONCLUSIONS: Males, particularly those aged ≥50 among skiers and 20-35 among snowboarders, should be wary of the potential for injuries to the head, neck, and airway when skiing or snowboarding. In this study, traumatic deaths from crashing into trees and asphyxiation from deep snow immersion accidents accounted for approximately half of fatal ski accidents in Japan.
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Accidentes , Asfixia , Masculino , Humanos , Japón/epidemiología , Estudios Retrospectivos , Asfixia/epidemiología , Asfixia/etiología , Proyectos de InvestigaciónRESUMEN
The superior petrosal sinus and petrosal vein are important drainage routes for the posterior cranial fossa, with some variations and collateral vessels. An anterolateral-type tentorial dural arteriovenous fistula, which occurs around the petrosal vein, often develops aggressive symptoms due to venous reflux to the brainstem and cerebellum. Neuroendovascular treatment of this fistula is usually challenging because transarterial embolization has a high risk and indications for transvenous embolization are limited. In the cavernous sinus and transverse sinus/sigmoid sinus dural arteriovenous fistulas, venous reflux to the petrosal vein is dangerous, and a treatment strategy with the occlusion of the petrosal vein is indispensable. Furthermore, attention should be paid to venous approaches through the superior petrosal sinus.
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Malformaciones Vasculares del Sistema Nervioso Central , Humanos , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Malformaciones Vasculares del Sistema Nervioso Central/terapia , Malformaciones Vasculares del Sistema Nervioso Central/cirugía , Senos Craneales/diagnóstico por imagen , Senos Craneales/cirugía , Venas Cerebrales/diagnóstico por imagen , Embolización Terapéutica/métodosRESUMEN
Preoperative embolization(POE)of intracranial meningioma is performed worldwide. Although clear evidence of the effectiveness of POE has not been reported in the literature, the technique plays an important role in open surgery, especially for large or skull base meningiomas. The purposes of embolization include: 1)induction of tumor necrosis, resulting in a safer operation, 2)reduction in intraoperative bleeding, and 3)decrease in operative time. Knowledge of the functional vascular anatomy, embolic materials, and endovascular techniques is paramount to ensure safe embolization. Our standard procedure is as follows: 1)embolization is performed several days before open surgery; 2)in cases with strong peritumoral edema, steroid administration or embolization may be performed immediately prior to surgery; 3)patients undergo the procedure under local anesthesia; 4)the microcatheter is inserted as close as possible to the tumor; 5)particulate emboli are the first-line material; 6)embolization is occasionally performed with N-butyl cyanoacrylate(NBCA)glue; and 7)if possible, additional proximal feeder occlusion with coils is performed. The JR-NET study previous showed the situation regarding intracranial tumor embolization in Japan. Endovascular neurosurgeons should fully discuss the indications and strategies for POE with tumor neurosurgeons to ensure safe and effective procedures.
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Embolización Terapéutica , Neoplasias Meníngeas , Meningioma , Cuidados Preoperatorios , Humanos , Embolización Terapéutica/métodos , Meningioma/cirugía , Meningioma/diagnóstico por imagen , Meningioma/terapia , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/terapia , Neoplasias Meníngeas/diagnóstico por imagenRESUMEN
The ventriculoperitoneal (VP) shunt is one of the most common surgical procedures in neurosurgery, frequently resulting in malfunctions. Shunt malfunctions, which can include mechanical failure, obstruction, infection, or disconnection, occur in a significant percentage of patients, often necessitating multiple revisions. These revisions can lead to increased healthcare costs due to additional surgeries or treatments. Therefore, addressing the economic impacts of these revisions is crucial. Our report presents a cost-effective approach to shunt revisions, demonstrated through a case study of an 82-year-old woman with hydrocephalus. Although initially treated with a VP shunt, she required a revision after six years due to shunt malfunction. Through comprehensive preoperative and intraoperative evaluations, including a shuntogram with iodine contrast and meticulous examination, we identified the cause of malfunction as a connective tissue sac blocking the peritoneal catheter. The surgery involved flushing the catheter lumen with saline to confirm the obstruction and careful removal of the obstructive tissue. This accurate diagnosis facilitated a minimally invasive revision, enabling the reuse of existing shunt components and avoiding the need for new devices, thus reducing costs and surgical invasiveness. Our study serves as a call to action for healthcare providers and surgeons to consider more cost-effective and patient-friendly approaches in managing VP shunt malfunctions, ultimately benefiting both the healthcare system and the patients it serves.
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Despite a long history of research, neurodegenerative diseases and malignant brain tumor gliomas are both considered incurable, facing challenges in the development of treatments. Recent evidence suggests that RNA modifications, previously considered as static components of intracellular RNAs, are in fact dynamically regulated across various RNA species in cells and play a critical role in major biological processes in the nervous system. Innovations in next-generation sequencing have enabled the accurate detection of modifications on bases and sugars within various RNA molecules. These RNA modifications influence the stability and transportation of RNA, and crucially affect its translation. This review delves into existing knowledge on RNA modifications to offer a comprehensive inventory of these modifications across different RNA species. The detailed regulatory functions and roles of RNA modifications within the nervous system are discussed with a focus on neurodegenerative diseases and gliomas. This article presents a comprehensive overview of the fundamental mechanisms and emerging roles of RNA modifications in these diseases, which can facilitate the creation of innovative diagnostics and therapeutics for these conditions.
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Neoplasias Encefálicas , Glioma , Enfermedades Neurodegenerativas , Humanos , Enfermedades Neurodegenerativas/patología , Glioma/genética , Neoplasias Encefálicas/genética , ARNRESUMEN
Gliomas with Isocitrate dehydrogenase (IDH) mutation represent a discrete category of primary brain tumors with distinct and unique characteristics, behaviors, and clinical disease outcomes. IDH mutations lead to aberrant high-level production of the oncometabolite D-2-hydroxyglutarate (D-2HG), which act as a competitive inhibitor of enzymes regulating epigenetics, signaling pathways, metabolism, and various other processes. This review summarizes the significance of IDH mutations, resulting upregulation of D-2HG and the associated molecular pathways in gliomagenesis. With the recent finding of clinically effective IDH inhibitors in these gliomas, this article offers a comprehensive overview of the new era of innovative therapeutic approaches based on mechanistic rationales, encompassing both completed and ongoing clinical trials targeting gliomas with IDH mutations.
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Neoplasias Encefálicas , Glioma , Isocitrato Deshidrogenasa , Mutación , Humanos , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/antagonistas & inhibidores , Glioma/tratamiento farmacológico , Glioma/genética , Glioma/patología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Inhibidores Enzimáticos/uso terapéutico , Inhibidores Enzimáticos/farmacología , Glutaratos/metabolismo , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Animales , Terapia Molecular DirigidaRESUMEN
BACKGROUND & AIMS: Muscle atrophy is an early event that occurs after stroke, but there are few reports on the changes in skeletal muscle thickness in acute stroke. This study investigated the factors contributing to reduced muscle thickness in patients with acute stroke. METHODS: In total, 51 patients with stroke and the National Institute of the Health Stroke Scale (NIHSS) > 3 were included in our study. They were admitted to our hospital between July 2017 and May 2020. The quadriceps muscle thickness was measured with an ultrasound device within 2 days after admission and 14 days later. The collected data included age, sex, body mass index, stroke type, neuromuscular electrical stimulation, NIHSS, serum albumin at admission, start of enteral nutrition, Functional Oral Intake Scale (FOIS), start of mobilization and ambulation, number of physical and occupational therapy units, C-reactive protein at admission and whether surgery had been performed. These data were retrospectively retrieved from medical documents. A dietician calculated energy intake, protein intake, and energy adequacy. Multiple regression analysis was used to identify the factors associated with reduced quadriceps muscle thickness. The independent variables were NIHSS, date of start of enteral feeding, protein intake, FOIS, date of mobilization, and date of start of ambulation training. RESULTS: The rate of change in quadriceps muscle thickness of the paretic limb was -15.3 % (interquartile range, -46.1-14.8 %). Multiple regression analysis showed that the factors responsible for the decrease in muscle thickness on the paretic side were FOIS (ß: 0.376; 95 % Cl, 0.999 to 4.541) and the start date of ambulation (ß: -0.378; 95 % Cl, -2.575 to -0.543), with a multiple correlation coefficient of 0.456. CONCLUSION: The FOIS and the start date of ambulation after acute stroke were related to the rate of reduction in muscle thickness on the paretic side.
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Músculo Cuádriceps , Accidente Cerebrovascular , Humanos , Músculo Cuádriceps/diagnóstico por imagen , Estudios Retrospectivos , Accidente Cerebrovascular/complicaciones , Músculo Esquelético , Atrofia Muscular/patologíaRESUMEN
The medulla oblongata is one of the rarest sites of occurrence for germ cell tumors (GCTs) of the central nervous system. As there is scant data regarding epidemiology, clinical presentations, optimal intervention, and long-term prognosis, we aimed to delineate the features of this rare entity by presenting our representative case and performing a quantitative review of the literature. A 24-year-old woman presented to our department with vertigo and swallowing difficulties. Magnetic resonance imaging revealed a homogenously enhanced exophytic lesion arising from the medulla oblongata and extending to the fourth ventricle. Surgical resection was performed and a histological diagnosis of pure germinoma was made. The patient underwent chemotherapy and whole-ventricular irradiation. No recurrence has been experienced for 4 months after the surgery. According to the literature, the prognosis of GCTs at the medulla oblongata seems no worse than those at typical sites. Striking features including occurrence at an older age, female preponderance, and a predominance of germinoma were noteworthy. The pattern of local recurrence suggests extensive radiation coverage is not a prerequisite. Special attention is needed for cardiac and respiratory functions as the main factors eliciting mortality.
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A chiral platinum(II) complex with a helical Schiff-base [4]helicene ligand exhibits intense red circularly polarized phosphorescence (CPP) with a glum of 0.010 in the dilute solution state. The intense CPP was caused by a change in the electronic transition character based on the induction of the helical structure.
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Surgical resection is considered for most brain tumors to obtain tissue diagnosis and to eradicate or debulk the tumor. Glioma, the most common primary malignant brain tumor, generally has a poor prognosis despite the multidisciplinary treatments with radical resection and chemoradiotherapy. Surgical resection of glioma is often complicated by the obscure border between the tumor and the adjacent brain tissues and by the tumor's infiltration into the eloquent brain. 5-aminolevulinic acid is frequently used for tumor visualization, as it exhibits high fluorescence in high-grade glioma. Here, we provide an overview of the fluorescent probes currently used for brain tumors, as well as those under development for other cancers, including HMRG-based probes, 2MeSiR-based probes, and other aminopeptidase probes. We describe our recently developed HMRG-based probes in brain tumors, such as PR-HMRG, combined with the existing diagnosis approach. These probes are remarkably effective for cancer cell recognition. Thus, they can be potentially integrated into surgical treatment for intraoperative detection of cancers.
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A woman in her 90s presented with loss of appetite, lower back pain, abdominal pain, and fever. Physical examination and subsequent blood tests indicated an inflammatory process, and computed tomography (CT) scans revealed gallbladder torsion with necrosis and abscess formation. The case involved successful management of this rare condition through percutaneous drainage without the need for surgical intervention, avoiding complications during follow-up. Remarkably, post-treatment CT showed complete resolution of the gallbladder abscess and the gallbladder itself was no longer visible. This case highlights the effectiveness of minimally invasive treatment for gallbladder torsion in elderly patients and underscores the potential for non-surgical intervention in managing complex abdominal conditions.
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This study aimed to identify the reasons for transferring athletes to local medical facilities during the Olympic and Paralympic Games. Data on 567 injuries and other illnesses of athletes treated at the on-site clinics were collected from the Tokyo 2020 Organizing Committee. Of these, 84 athletes who required outpatient care during the Games were registered for this survey. During the Olympic and Paralympic Games, 66 (8.3/1 000) and 18 (7.2/1 000) athletes, respectively, consulted external medical facilities. In the Olympic Games, the reasons for these visits included 48 cases (72.7%) of injuries, 13 (19.7%) cases of illnesses, and 5 (7.6%) cases of heat stroke illness (HSI). Of these patients, 56 (84.9%) were treated as outpatients and 10 (15.1%) were hospitalized, while three of these patients required hospitalization for > 7 days. On the other hand, in the Paralympics Games, there were 7 (38.8%) cases of injuries, 9 (50.0%) other illnesses, 1 (5.6%) case of HSI, and 1 (5.6%) other cases, of which 11 (61.1%) were treated as outpatients and 7 (38.9%) were hospitalized, but none was hospitalized for > 7 days. Injuries accounted for 70% of the total cases at the 2021 Olympic Games, but only three (0.05%) were severe cases that required hospitalization for more than 1 week. In contrast, in the Paralympic Games, other illnesses accounted for approximately half of the total cases. This study provides details on the extent of injuries and other illnesses that were transferred to outside facilities, which has not been documented in previous games.
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Background: Glioblastoma (GBM) is a highly lethal brain tumor. The effectiveness of temozolomide (TMZ) treatment in GBM is linked to the methylation status of O6-methyl-guanine DNA methyltransferase (MGMT) promoter. Patients with unmethylated MGMT promoter have limited treatment options available. Consequently, there is a pressing need for alternative therapeutic strategies for such patients. Methods: Data, including transcriptomic and clinical information, as well as information on MGMT promoter methylation status in primary GBM, were obtained from The Cancer Genome Atlas (TCGA) (n=121) and Chinese Glioma Genome Atlas (CGGA) (n=83) datasets. Samples were categorized into high and low MGMT expression groups, MGMT-high (MGMT-H) and MGMT-low (MGMT-L) tumors. A comprehensive transcriptome analysis was conducted to explore the tumor-immune microenvironment. Furthermore, we integrated transcriptome data from 13 GBM patients operated at our institution with findings from tumor-infiltrating lymphocyte (TIL) cultures, specifically investigating their response to autologous tumors. Results: Gene signatures associated with various immune cells, including CD8 T cells, helper T cells, B cells, and macrophages, were noted in MGMT-H tumors. Pathway analysis confirmed the enrichment of immune cell-related pathways. Additionally, biological processes involved in the activation of monocytes and lymphocytes were observed in MGMT-H tumors. Furthermore, TIL culture experiments showed a greater presence of tumor-reactive T cells in MGMT-H tumors compared to MGMT-L tumors. These findings suggest that MGMT-H tumors has a potential for enhanced immune response against tumors mediated by CD8 T cells. Conclusion: Our study provides novel insights into the immune cell composition of MGMT-H tumors, which is characterized by the infiltration of type 1 helper T cells and activated B cells, and also the presence of tumor-reactive T cells evidenced by TIL culture. These findings contribute to a better understanding of the immune response in MGMT-H tumors, emphasizing their potential for immunotherapy. Further studies are warranted to investigate on the mechanisms of MGMT expression and antitumor immunity.