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1.
J Korean Med Sci ; 39(9): e88, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38469964

RESUMO

BACKGROUND: Liver transplantation (LT) patients appear to be more prone to neurological events compared to individuals undergoing other types of solid-organ transplantation. The aims of the present study were to analyze the prevalence of unruptured intracranial aneurysms (UIAs) in patients undergoing liver transplantation (LT) and to examine the perioperative occurrence of subarachnoid hemorrhage (SAH). Also, it intended to systematically identify the risk factors of SAH and hemorrhagic stroke (HS) within a year after LT and to develop a scoring system which involves distinct clinical features of LT patients. METHODS: Patients who underwent LT from January 2012 to March 2022 were analyzed. All included patients underwent neurovascular imaging within 6 months before LT. We conducted an analysis of prevalence and radiological features of UIA and SAH. The clinical factors that may have an impact on HS within one year of LT were also reviewed. RESULTS: Total of 3,487 patients were enrolled in our study after applying inclusion and exclusion criteria. The prevalence of UIA was 5.4%. The incidence of SAH and HS within one year following LT was 0.5% and 1.6%, respectively. We developed a scoring system based on multivariable analysis to predict the HS within 1-year after LT. The variables were a poor admission mental status, the diagnosis of UIA, serum ammonia levels, and Model for End-stage Liver Disease (MELD) scores. Our model showed good discrimination among the development (C index, 0.727; 95% confidence interval [CI], 0.635-0.820) and validation (C index, 0.719; 95% CI, 0.598-0.801) cohorts. CONCLUSION: The incidence of UIA and SAH was very low in LT patients. A poor admission mental status, diagnosis of UIA, serum ammonia levels, and MELD scores were significantly associated with the risk of HS within one year after LT. Our scoring system showed a good discrimination to predict the HS in LT patients.


Assuntos
Doença Hepática Terminal , Acidente Vascular Cerebral Hemorrágico , Aneurisma Intracraniano , Transplante de Fígado , Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Humanos , Aneurisma Intracraniano/diagnóstico , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/cirurgia , Acidente Vascular Cerebral Hemorrágico/complicações , Transplante de Fígado/efeitos adversos , Amônia , Doença Hepática Terminal/complicações , Índice de Gravidade de Doença , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/etiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
2.
ACS Nano ; 18(9): 7180-7191, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38373269

RESUMO

The need for reliable renewable energy storage devices has become increasingly important. However, the performance of current electrochemical energy storage devices is limited by either low energy or power densities and short lifespans. Herein, we report the synthesis and characterization of multilayer Ti4N3Tx MXene in various aqueous electrolytes. We demonstrate that Ti4N3Tx can be electrochemically activated through continuous cation intercalation over a 10 day period using cyclic voltammetry. A wide operating window of 2 V is maintained throughout activation. After activation, capacitance at 2 mV s-1 increases by 300%, 140%, and 500% in 1 M H2SO4, 1 M MgSO4, and 1 M KOH, respectively, while maintaining ∼600 F g-1 at 2 mV s-1 after 50000 cycles in 1 M H2SO4. This activation process is possibly attributed to the unique morphology of the multilayered material, allowing cation intercalation to increase access to redox-active sites between layers. This work adds to the growing repository of electrochemically stable MXenes reported for aqueous energy storage applications. These findings offer a reliable option for reliable energy storage devices with potential applications in large-scale grid storage and electric vehicles.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38389227

RESUMO

Objective: We evaluated the role of subgaleal closed suction drains in postoperative epidural hematoma (EDH) and wound complications following pterional craniotomy for cerebral aneurysm. Methods: We reviewed 5,280 pterional craniotomies performed on 5,139 patients between January 2006 and December 2020. A drain was placed subgalealy and tip of drain was positioned between the bone flap and the deep temporalis. 1,637 cases (31%) had a subgaleal suction drain. We analyzed demographic and clinical variables related to EDH requiring evacuation and wound complications in patients with and without drains. Univariate and multivariate logistic regression analyses were performed to determine the associated risk factors. Results: Fourteen cases (0.27%) of EDH requiring evacuation and 30 cases (0.57%) of wound complications were identified. Univariate analysis found that drain insertion, subarachnoid hemorrhage (SAH), and operation time were associated with EDH, while drain insertion, SAH, male gender, older age, and longer operation time were associated with wound complications. Multivariate analysis found no significant association between drain use and EDH (OR=1.62, p=0.402) or wound complications (OR=1.45, p=0.342). Conclusions: Routine use of subgaleal closed suction drains may not be necessary after pterional craniotomy, as drain insertion was not associated with a reduced risk of EDH requiring evacuation or wound complications.

4.
Sci Rep ; 14(1): 56, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167529

RESUMO

To investigate the association between chemical markers (triglyceride, C-reactive protein (CRP), and inflammation markers) and perfusion markers (relative cerebral vascular reserve (rCVR)) with moyamoya disease progression and complication types. A total of 314 patients diagnosed with moyamoya disease were included. Triglyceride and CRP levels were assessed and categorized based on Korean guidelines for dyslipidemia and CDC/AHA guidelines, respectively. Perfusion markers were evaluated using Diamox SPECT. Cox proportional hazard analysis was performed to examine the relationship between these markers and disease progression, as well as complication types (ischemic stroke, hemorrhagic stroke, and rCVR deterioration). Elevated triglyceride levels (≥ 200) were significantly associated with higher likelihood of end-point events (HR: 2.292, CI 1.00-4.979, P = 0.03). Severe decreased rCVR findings on Diamox SPECT were also significantly associated with end-point events (HR: 3.431, CI 1.254-9.389, P = 0.02). Increased CRP levels and white blood cell (WBC) count were significantly associated with moyamoya disease progression. For hemorrhagic stroke, higher triglyceride levels were significantly associated with end-point events (HR: 5.180, CI 1.355-19.801, P = 0.02). For ischemic stroke, severe decreased rCVR findings on Diamox SPECT (HR: 5.939, CI 1.616-21.829, P < 0.01) and increased CRP levels (HR: 1.465, CI 1.009-2.127, P = 0.05) were significantly associated with end-point events. Elevated triglyceride, CRP, and inflammation markers, as well as decreased rCVR, are potential predictors of moyamoya disease progression and complication types. Further research is warranted to understand their role in disease pathophysiology and treatment strategies.


Assuntos
Acidente Vascular Cerebral Hemorrágico , AVC Isquêmico , Doença de Moyamoya , Acidente Vascular Cerebral , Humanos , Acetazolamida , Acidente Vascular Cerebral Hemorrágico/complicações , Perfusão/efeitos adversos , Proteína C-Reativa , Progressão da Doença , AVC Isquêmico/complicações , Inflamação/complicações , Triglicerídeos , Acidente Vascular Cerebral/complicações
5.
J Korean Neurosurg Soc ; 66(6): 618-631, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37840243

RESUMO

The brain houses vital hormonal regulatory structures such as the hypothalamus and pituitary gland, which may confer unique susceptibilities to critical illness-related corticosteroid insufficiency (CIRCI) in patients with neurological disorders. In addition, the frequent use of steroids for therapeutic purposes in various neurological conditions may lead to the development of steroid insufficiency. This abstract aims to highlight the significance of understanding these relationships in the context of patient care and management for physicians. Neurological disorders may predispose patients to CIRCI due to the role of the brain in hormonal regulation. Early recognition of CIRCI in the context of neurological diseases is essential to ensure prompt and appropriate intervention. Moreover, the frequent use of steroids for treating neurological conditions can contribute to the development of steroid insufficiency, further complicating the clinical picture. Physicians must be aware of these unique interactions and be prepared to evaluate and manage patients with CIRCI and steroid insufficiency in the context of neurological disorders. This includes timely diagnosis, appropriate steroid administration, and careful monitoring for potential adverse effects. A comprehensive understanding of the interplay between neurological disease, CIRCI, and steroid insufficiency is critical for optimizing patient care and outcomes in this complex patient population.

6.
Mol Neurobiol ; 60(11): 6212-6226, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37436602

RESUMO

Cognitive impairment refers to notable declines in cognitive abilities including memory, language, and emotional stability leading to the inability to accomplish essential activities of daily living. Astrocytes play an important role in cognitive function, and homeostasis of the astrocyte-neuron lactate shuttle (ANLS) system is essential for maintaining cognitive functions. Aquaporin-4 (AQP-4) is a water channel expressed in astrocytes and has been shown to be associated with various brain disorders, but the direct relationship between learning, memory, and AQP-4 is unclear. We examined the relationship between AQP-4 and cognitive functions related to learning and memory. Mice with genetic deletion of AQP-4 showed significant behavioral and emotional changes including hyperactivity and instability, and impaired cognitive functions such as spatial learning and memory retention. 18 F-FDG PET imaging showed significant metabolic changes in the brains of AQP-4 knockout mice such as reductions in glucose absorption. Such metabolic changes in the brain seemed to be the direct results of changes in the expression of metabolite transporters, as the mRNA levels of multiple glucose and lactate transporters in astrocytes and neurons were significantly decreased in the cortex and hippocampus of AQP-4 knockout mice. Indeed, AQP-4 knockout mice showed significantly higher accumulation of both glucose and lactate in their brains compared with wild-type mice. Our results show that the deficiency of AQP-4 can cause problems in the metabolic function of astrocytes and lead to cognitive impairment, and that the deficiency of AQP4 in astrocyte endfeet can cause abnormalities in the ANLS system.


Assuntos
Aquaporina 4 , Disfunção Cognitiva , Ácido Láctico , Animais , Humanos , Camundongos , Aquaporina 4/genética , Aquaporina 4/metabolismo , Astrócitos/metabolismo , Disfunção Cognitiva/metabolismo , Glucose/metabolismo , Ácido Láctico/metabolismo , Camundongos Knockout , Neurônios/metabolismo
7.
Korean J Neurotrauma ; 19(2): 128-148, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37431371

RESUMO

Decompressive craniectomy (DCE) and cranioplasty (CP) are surgical procedures used to manage elevated intracranial pressure (ICP) in various clinical scenarios, including ischemic stroke, hemorrhagic stroke, and traumatic brain injury. The physiological changes following DCE, such as cerebral blood flow, perfusion, brain tissue oxygenation, and autoregulation, are essential for understanding the benefits and limitations of these procedures. A comprehensive literature search was conducted to systematically review the recent updates in DCE and CP, focusing on the fundamentals of DCE for ICP reduction, indications for DCE, optimal sizes and timing for DCE and CP, the syndrome of trephined, and the debate on suboccipital CP. The review highlights the need for further research on hemodynamic and metabolic indicators following DCE, particularly in relation to the pressure reactivity index. It provides recommendations for early CP within three months of controlling increased ICP to facilitate neurological recovery. Additionally, the review emphasizes the importance of considering suboccipital CP in patients with persistent headaches, cerebrospinal fluid leakage, or cerebellar sag after suboccipital craniectomy. A better understanding of the physiological effects, indications, complications, and management strategies for DCE and CP to control elevated ICP will help optimize patient outcomes and improve the overall effectiveness of these procedures.

8.
Korean J Neurotrauma ; 19(2): 162-176, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37431377

RESUMO

Mannitol, derived from mannose sugar, is crucial in treating patients with elevated intracranial pressure (ICP). Its dehydrating properties at the cellular and tissue levels increase plasma osmotic pressure, which is studied for its potential to reduce ICP through osmotic diuresis. While clinical guidelines support mannitol use in these cases, the best approach for its application continues to be debated. Important aspects needing further investigation include: 1) bolus administration versus continuous infusion, 2) ICP-based dosing versus scheduled bolus, 3) identifying the optimal infusion rate, 4) determining the appropriate dosage, 5) establishing fluid replacement plans for urinary loss, and 6) selecting monitoring techniques and thresholds to assess effectiveness and ensure safety. Due to the lack of adequate high-quality prospective research data, a comprehensive review of recent studies and clinical trials is crucial. This assessment aims to bridge the knowledge gap, improve understanding of effective mannitol use in elevated ICP patients, and provide insights for future research. In conclusion, this review aspires to contribute to the ongoing discourse on mannitol application. By integrating the latest findings, this review will offer valuable insights into the function of mannitol in decreasing ICP, thereby informing better therapeutic approaches and enhancing patient outcomes.

9.
J Korean Med Sci ; 38(21): e161, 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37270916

RESUMO

BACKGROUND: Subarachnoid hemorrhage (SAH) patients have oxidative stress results in inflammation, tissue degeneration and neuronal damage. These deleterious effects cause aggravation of the perihematomal edema (PHE), vasospasm, and even hydrocephalus. We hypothesized that antioxidants may have a neuroprotective role in acute aneurysmal SAH (aSAH) patients. METHODS: We conducted a prospective, multicenter randomized (single blind) trial between January 2017 and October 2019, investigating whether antioxidants (acetylcysteine and selenium) have the potential to improve the neurologic outcome in aSAH patients. The antioxidant patient group received antioxidants of acetylcysteine (2,000 mg/day) and selenium (1,600 µg/day) intravenously (IV) for 14 days. These drugs were administrated within 24 hours of admission. The non-antioxidant patient group received a placebo IV. RESULTS: In total, 293 patients were enrolled with 103 patients remaining after applying the inclusion and exclusion criteria. No significant differences were observed in the baseline characteristics between the antioxidant (n = 53) and non-antioxidant (n = 50) groups. Among clinical factors, the duration of intensive care unit (ICU) stay was significantly shortened in patients who received antioxidants (11.2, 95% confidence interval [CI], 9.7-14.5 vs. 8.3, 95% CI, 6.2-10.2 days, P = 0.008). However, no beneficial effects were observed on radiological outcomes. CONCLUSION: In conclusion, antioxidant treatment failed to show the reduction of PHE volume, mid-line shifting, vasospasm and hydrocephalus in acute SAH patients. A significant reduction in ICU stay was observed but need more optimal dosing schedule and precise outcome targets are required to clarify the clinical impacts of antioxidants in these patients. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0004628.


Assuntos
Hidrocefalia , Selênio , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Acetilcisteína/uso terapêutico , Selênio/uso terapêutico , Estudos Prospectivos , Método Simples-Cego , Resultado do Tratamento , Hidrocefalia/etiologia , Hidrocefalia/complicações
10.
Artigo em Inglês | MEDLINE | ID: mdl-37308453

RESUMO

The brain houses vital hormonal regulatory structures such as the hypothalamus and pituitary gland, which may confer unique susceptibilities to critical illness-related corticosteroid insufficiency (CIRCI) in patients with neurological disorders. In addition, the frequent use of steroids for therapeutic purposes in various neurological conditions may lead to the development of steroid insufficiency. This abstract aims to highlight the significance of understanding these relationships in the context of patient care and management for physicians. Neurological disorders may predispose patients to CIRCI due to the role of the brain in hormonal regulation. Early recognition of CIRCI in the context of neurological diseases is essential to ensure prompt and appropriate intervention. Moreover, the frequent use of steroids for treating neurological conditions can contribute to the development of steroid insufficiency, further complicating the clinical picture. Physicians must be aware of these unique interactions and be prepared to evaluate and manage patients with CIRCI and steroid insufficiency in the context of neurological disorders. This includes timely diagnosis, appropriate steroid administration, and careful monitoring for potential adverse effects. A comprehensive understanding of the interplay between neurological disease, CIRCI, and steroid insufficiency is critical for optimizing patient care and outcomes in this complex patient population.

11.
Nucleic Acids Res ; 51(13): 6540-6553, 2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37254785

RESUMO

Bacteriophage T7 single-stranded DNA-binding protein (gp2.5) binds to and protects transiently exposed regions of single-stranded DNA (ssDNA) while dynamically interacting with other proteins of the replication complex. We directly visualize fluorescently labelled T7 gp2.5 binding to ssDNA at the single-molecule level. Upon binding, T7 gp2.5 reduces the contour length of ssDNA by stacking nucleotides in a force-dependent manner, suggesting T7 gp2.5 suppresses the formation of secondary structure. Next, we investigate the binding dynamics of T7 gp2.5 and a deletion mutant lacking 21 C-terminal residues (gp2.5-Δ21C) under various template tensions. Our results show that the base sequence of the DNA molecule, ssDNA conformation induced by template tension, and the acidic terminal domain from T7 gp2.5 significantly impact on the DNA binding parameters of T7 gp2.5. Moreover, we uncover a unique template-catalyzed recycling behaviour of T7 gp2.5, resulting in an apparent cooperative binding to ssDNA, facilitating efficient spatial redistribution of T7 gp2.5 during the synthesis of successive Okazaki fragments. Overall, our findings reveal an efficient binding mechanism that prevents the formation of secondary structures by enabling T7 gp2.5 to rapidly rebind to nearby exposed ssDNA regions, during lagging strand DNA synthesis.


Assuntos
Bacteriófago T7 , Proteínas Virais , Bacteriófago T7/genética , DNA/metabolismo , Replicação do DNA , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/metabolismo , Conformação Molecular , Proteínas Virais/metabolismo
12.
Sensors (Basel) ; 23(8)2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37112234

RESUMO

The Light Detection and Ranging (LiDAR) sensor has become essential to achieving a high level of autonomous driving functions, as well as a standard Advanced Driver Assistance System (ADAS). LiDAR capabilities and signal repeatabilities under extreme weather conditions are of utmost concern in terms of the redundancy design of automotive sensor systems. In this paper, we demonstrate a performance test method for automotive LiDAR sensors that can be utilized in dynamic test scenarios. In order to measure the performance of a LiDAR sensor in a dynamic test scenario, we propose a spatio-temporal point segmentation algorithm that can separate a LiDAR signal of moving reference targets (car, square target, etc.), using an unsupervised clustering method. An automotive-graded LiDAR sensor is evaluated in four harsh environmental simulations, based on time-series environmental data of real road fleets in the USA, and four vehicle-level tests with dynamic test cases are conducted. Our test results showed that the performance of LiDAR sensors may be degraded, due to several environmental factors, such as sunlight, reflectivity of an object, cover contamination, and so on.

13.
Clin Neurol Neurosurg ; 228: 107703, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37058770

RESUMO

OBJECTIVE: Many neurosurgeons routinely perform postoperative intensive care unit (ICU) management after clipping of unruptured intracranial aneurysms (UIAs). However, whether routine postoperative ICU care is necessary remains a clinical question. Therefore, we investigated which factors acted as risk factors that actually required ICU care after microsurgical clipping of unruptured aneurysms. METHODS: We included a total of 532 patients who underwent clipping surgery for UIA between January 2020 and December 2020. The patients were divided into two groups: those who really required ICU care (41 patients, 7.7%) and those who did not (491 patients, 92.3%). A backward stepwise logistic regression model was used to identify factors that were independently associated with ICU care requirement. RESULTS: The mean hospital stay duration and the operation time were significantly longer in the ICU requirement group than in the no ICU requirement group (9.9 ± 10.7 vs. 6.3 ± 3.7 days, p = 0.041), (259.9 ± 128.4 vs. 210.5 ± 46.1 min, p = 0.019). The transfusion rate was significantly higher (p = 0.024) in the ICU requirement group. Multivariable logistic regression analysis identified male sex (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.15-4.76; p = 0.0195), operation time (OR, 1.01; 95% CI, 1.00-1.01; p = 0.0022), and transfusion (OR, 2.35; 95% CI, 1.00-5.51; p = 0.0500) as independent risk factors for requiring ICU care after clipping. CONCLUSIONS: Postoperative ICU management may not be mandatory after clipping surgery for UIAs. Our results suggest that postoperative ICU management may be more required in the male sex, patients with longer operation times, and those who received a transfusion.


Assuntos
Aneurisma Intracraniano , Humanos , Masculino , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/etiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Tempo de Internação , Instrumentos Cirúrgicos , Fatores de Risco , Estudos Retrospectivos , Resultado do Tratamento
14.
J Transl Med ; 21(1): 69, 2023 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-36732815

RESUMO

BACKGROUND: Recurrence is common in glioblastoma multiforme (GBM) because of the infiltrative, residual cells in the tumor margin. Standard therapy for GBM consists of surgical resection followed by chemotherapy and radiotherapy, but the median survival of GBM patients remains poor (~ 1.5 years). For recurrent GBM, anti-angiogenic treatment is one of the common treatment approaches. However, current anti-angiogenic treatment modalities are not satisfactory because of the resistance to anti-angiogenic agents in some patients. Therefore, we sought to identify novel prognostic biomarkers that can predict the therapeutic response to anti-angiogenic agents in patients with recurrent glioblastoma. METHODS: We selected patients with recurrent GBM who were treated with anti-angiogenic agents and classified them into responders and non-responders to anti-angiogenic therapy. Then, we performed proteomic analysis using liquid-chromatography mass spectrometry (LC-MS) with formalin-fixed paraffin-embedded (FFPE) tissues obtained from surgical specimens. We conducted a gene-ontology (GO) analysis based on protein abundance in the responder and non-responder groups. Based on the LC-MS and GO analysis results, we identified potential predictive biomarkers for anti-angiogenic therapy and validated them in recurrent glioblastoma patients. RESULTS: In the mass spectrometry-based approach, 4957 unique proteins were quantified with high confidence across clinical parameters. Unsupervised clustering analysis highlighted distinct proteomic patterns (n = 269 proteins) between responders and non-responders. The GO term enrichment analysis revealed a cluster of genes related to immune cell-related pathways (e.g., TMEM173, FADD, CD99) in the responder group, whereas the non-responder group had a high expression of genes related to nuclear replisome (POLD) and damaged DNA binding (ERCC2). Immunohistochemistry of these biomarkers showed that the expression levels of TMEM173 and FADD were significantly associated with the overall survival and progression-free survival of patients with recurrent GBM. CONCLUSIONS: The candidate biomarkers identified in our protein analysis may be useful for predicting the clinical response to anti-angiogenic agents in patients with recurred GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Proteômica , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Recidiva Local de Neoplasia/genética , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Biomarcadores , Proteína Grupo D do Xeroderma Pigmentoso
15.
Acta Neurochir (Wien) ; 165(2): 501-515, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36652012

RESUMO

PURPOSE: An anterior communicating artery is a common location for both ruptured and unruptured intracranial aneurysms, and microsurgery is sometimes necessary for their successful treatment. However, postoperative infarction should be considered during clipping due to the complex surrounding structures of anterior communicating artery aneurysms. This study aimed to evaluate the risk factors of postoperative infarction after surgical clipping of unruptured anterior communicating artery aneurysms and its clinical outcomes. METHODS: The data of patients who underwent microsurgical clipping of an unruptured anterior communicating artery aneurysm in our hospital between January 2008 and December 2020 were retrospectively analyzed. The patients' demographic data, anatomical features of the anterior communicating artery complex and aneurysm, surgical technique, characteristics of postoperative infarction, and its clinical course were evaluated. RESULTS: Notably, among 848 patients, 66 (7.8%) and 34 (4%) patients had radiologic and symptomatic infarctions, respectively. Univariate and multivariate logistic regression analyses showed that hypertension (odds ratio (OR), 1.99; [Formula: see text]), previous stroke (OR, 3.89; [Formula: see text]), posterior projection (OR, 5.58; [Formula: see text]), aneurysm size (OR, 1.17; optimal cut-off value, 6.14 mm; [Formula: see text]), and skull base-to-aneurysm distance (OR, 1.15; optimal cut-off value, 11.09 mm; [Formula: see text]) were associated with postoperative infarction. In the pterional approach, a closed A2 plane was an additional risk factor (OR, 1.88; [Formula: see text]). Infarction of the subcallosal and hypothalamic branches was significantly associated with symptomatic infarction ([Formula: see text]). CONCLUSION: Hypertension, previous stroke, posteriorly projecting aneurysms, aneurysm size, and highly positioned aneurysms are independent risk factors for postoperative infarction during surgical clipping of an unruptured anterior communicating artery aneurysm. Additionally, a closed A2 plane is an additional risk factor of postoperative infarction in patients undergoing clipping via the pterional approach.


Assuntos
Aneurisma Roto , Aneurisma Intracraniano , Acidente Vascular Cerebral , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/complicações , Estudos Retrospectivos , Infarto/complicações , Fatores de Risco , Acidente Vascular Cerebral/complicações , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/cirurgia , Aneurisma Roto/complicações , Resultado do Tratamento
16.
Nat Biotechnol ; 41(5): 686-697, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36624149

RESUMO

Cytosine base editors (CBEs) enable programmable genomic C·G-to-T·A transition mutations and typically comprise a modified CRISPR-Cas enzyme, a naturally occurring cytidine deaminase, and an inhibitor of uracil repair. Previous studies have shown that CBEs utilizing naturally occurring cytidine deaminases may cause unguided, genome-wide cytosine deamination. While improved CBEs that decrease stochastic genome-wide off-targets have subsequently been reported, these editors can suffer from suboptimal on-target performance. Here, we report the generation and characterization of CBEs that use engineered variants of TadA (CBE-T) that enable high on-target C·G to T·A across a sequence-diverse set of genomic loci, demonstrate robust activity in primary cells and cause no detectable elevation in genome-wide mutation. Additionally, we report cytosine and adenine base editors (CABEs) catalyzing both A-to-I and C-to-U editing (CABE-Ts). Together with ABEs, CBE-Ts and CABE-Ts enable the programmable installation of all transition mutations using laboratory-evolved TadA variants with improved properties relative to previously reported CBEs.


Assuntos
Citosina , Edição de Genes , Mutação/genética , Citidina Desaminase/genética , Genoma , Sistemas CRISPR-Cas/genética
17.
Brain Tumor Res Treat ; 10(3): 172-182, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35929115

RESUMO

BACKGROUND: There are numerous factors to consider in deciding whether to undergo surgical treatment for brain metastasis from lung cancer. Herein, we aimed to analyze the survival outcome and predictors of recurrence of surgically treated brain metastasis from non-small cell lung cancer (NSCLC). METHODS: A total of 197 patients with brain metastasis from NSCLC who underwent microsurgery were included in this study. RESULTS: A total of 114 (57.9%) male and 83 (42.1%) female patients with a median age of 59 years (range, 27-79) was included in this study. The median follow-up period was 22.7 (range, 1-126) months. The 1-year and 2-year overall survival (OS) rates of patients with brain metastasis secondary to NSCLC were 59% and 43%, respectively. The 6-month and 1-year progression-free survival (PFS) rates of local recurrence were 80% and 73%, respectively, whereas those of distant recurrence were 84% and 63%, respectively. En-bloc resection of tumor resulted in better PFS for local recurrence (1-year PFS: 79% vs. 62%, p=0.02). Ventricular opening and direct contact between the tumor and the subarachnoid space were not associated with distal recurrence and leptomeningeal seeding. The difference in PFS of local recurrence according to adjuvant resection bed irradiation was not significant. Moreover, postoperative whole-brain irradiation did not show a significant difference in PFS of distant recurrence. In multivariate analysis, only en-bloc resection was a favorable prognostic factor for local recurrence. Contrastingly, multiple metastasis was a poor prognostic factor for distant recurrence. CONCLUSION: En-bloc resection may reduce local recurrence after surgical resection. Ventricular opening and contact between the tumor and subarachnoid space did not show a statistically significant result for distant recurrence and leptomeningeal seeding. Multiple metastasis was only meaningful factor for distant recurrence.

18.
J Biol Chem ; 298(6): 101996, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35500649

RESUMO

The T7 primase-helicase plays a pivotal role in the replication of T7 DNA. Using affinity isolation of peptide-nucleic acid crosslinks and mass spectrometry, we identify protein regions in the primase-helicase and T7 DNA polymerase that form contacts with the RNA primer and DNA template. The contacts between nucleic acids and the primase domain of the primase-helicase are centered in the RNA polymerase subdomain of the primase domain, in a cleft between the N-terminal subdomain and the topoisomerase-primase fold. We demonstrate that residues along a beta sheet in the N-terminal subdomain that contacts the RNA primer are essential for phage growth and primase activity in vitro. Surprisingly, we found mutations in the primase domain that had a dramatic effect on the helicase. Substitution of a residue conserved in other DnaG-like enzymes, R84A, abrogates both primase and helicase enzymatic activities of the T7 primase-helicase. Alterations in this residue also decrease binding of the primase-helicase to ssDNA. However, mass photometry measurements show that these mutations do not interfere with the ability of the protein to form the active hexamer.


Assuntos
Bacteriófago T7 , DNA Helicases , DNA Primase , DNA , Proteínas Virais , Sequência de Aminoácidos , Bacteriófago T7/enzimologia , DNA/metabolismo , DNA Helicases/química , DNA Helicases/metabolismo , DNA Primase/química , DNA Primase/genética , DNA Primase/metabolismo , Mutação , Proteínas Virais/química , Proteínas Virais/metabolismo
19.
Molecules ; 27(8)2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35458627

RESUMO

The volatile compounds and sensory profiles of 18 different types of distilled soju, chosen with regard to various raw materials and distillation methods (atmospheric vs. vacuum), were explored using headspace solid-phase microextraction (HS-SPME) with gas chromatography-mass spectrometry (GC-MS) and descriptive analysis. General chemical properties such as pH, total acidity (TA), total soluble solids (°Brix), and lactic acid concentration were also determined. A total of 56 volatile compounds, comprising 31 esters, 11 alcohols, 1 acid, 4 aldehydes, 3 ketones, and 6 miscellaneous compounds, were identified. From the principal component analysis (PCA) of the volatile data, samples made using atmospheric distillation such as MSO and PJU showed a clear difference from decompressed distillation samples. Based on the PCA of the sensory data, there was also a clear distinction between samples by their distillation method. To explore relationships among chemical, volatile, and sensory data sets, multiple factor analysis (MFA) was applied. Yeasty and earthy flavors showed a close relationship with 1-nonanol, octatonic acid, and longer-chain esters such as ethyl phenylacetate and ethyl tetradecanoate, and with chemical parameters such as TA, °Brix, and lactic acid.


Assuntos
Microextração em Fase Sólida , Compostos Orgânicos Voláteis , Ésteres/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Ácido Láctico/análise , República da Coreia , Microextração em Fase Sólida/métodos , Compostos Orgânicos Voláteis/análise
20.
Neurosurg Rev ; 45(3): 2457-2470, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35304692

RESUMO

Posterior communicating artery (PCoA) aneurysm is common and sometimes requires microsurgery; however, as data on premammillary artery (PMA) infarction after clipping is scarce, we retrospectively reviewed cases of post-clipping PMA infarction to analyze incidence, independent risk factors of infarction, and anatomical considerations. Data from 569 consecutive patients who underwent microsurgical clipping for unruptured PCoA aneurysm between January 2008 and December 2020 were included. Patients were categorized into the normal or the PMA infarction group. Statistical analyses and comparisons between the two groups were used to determine the influence of various factors. The normal group included 515 patients while the PMA infarction group had 31. The mean length of hospital stay was significantly longer in the PMA infarction group (10.3 ± 9.1 days) than in the normal group (6.5 ± 6.4 days; p < 0.0001). The distribution of Glasgow Outcome Scale at discharge was significantly different between the two groups (p ≤ 0.0001) but was not so at 6 months after discharge (p = 0.0568). Multivariate logistic regression analysis identified aneurysm size (odds ratio [OR], 1.194; 95% confidence interval [CI], 1.08-1.32; p = 0.0005) and medial direction of aneurysm (OR, 4.615; 95% CI, 1.224-17.406; p = 0.0239) as independent risk factors of post-clipping PMA infarction. Surgeons must beware of PMA infarction after clipping of large aneurysms that are medial in direction. Intraoperative verification of the patency of the PCoA and the PMA from various angles using various intraoperative methods can reduce morbidity due to PMA infarction.


Assuntos
Aneurisma Roto , Aneurisma Intracraniano , Aneurisma Roto/cirurgia , Artérias , Humanos , Infarto/etiologia , Infarto/cirurgia , Aneurisma Intracraniano/etiologia , Aneurisma Intracraniano/cirurgia , Microcirurgia/efeitos adversos , Microcirurgia/métodos , Procedimentos Neurocirúrgicos/métodos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
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