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1.
J Neuroeng Rehabil ; 21(1): 115, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987817

RESUMO

BACKGROUND: Stroke causes long-term disabilities, highlighting the need for innovative rehabilitation strategies for reducing residual impairments. This study explored the potential of functional near-infrared spectroscopy (fNIRS) for monitoring cortical activation during rehabilitation using digital therapeutics. METHODS: This cross-sectional study included 18 patients with chronic stroke, of whom 13 were men. The mean age of the patients was 67.0 ± 7.1 years. Motor function was evaluated through various tests, including the Fugl-Meyer assessment for upper extremity (FMA-UE), grip and pinch strength test, and box and block test. All the patients completed the digital rehabilitation program (MotoCog®, Cybermedic Co., Ltd., Republic of Korea) while being monitored using fNIRS (NIRScout®, NIRx Inc., Germany). Statistical parametric mapping (SPM) was employed to analyze the cortical activation patterns from the fNIRS data. Furthermore, the K-nearest neighbor (K-NN) algorithm was used to analyze task performance and fNIRS data to classify the severity of motor impairment. RESULTS: The participants showed diverse task performances in the digital rehabilitation program, demonstrating distinct patterns of cortical activation that correlated with different motor function levels. Significant activation was observed in the ipsilesional primary motor area (M1), primary somatosensory area (S1), and contralateral prefrontal cortex. The activation patterns varied according to the FMA-UE scores. Positive correlations were observed between the FMA-UE scores and SPM t-values in the ipsilesional M1, whereas negative correlations were observed in the ipsilesional S1, frontal lobe, and parietal lobe. The incorporation of cortical hemodynamic responses with task scores in a digital rehabilitation program substantially improves the accuracy of the K-NN algorithm in classifying upper limb functional levels in patients with stroke. The accuracy for tasks, such as the gas stove-operation task, increased from 44.4% using only task scores to 83.3% when these scores were combined with oxy-Hb t-values from the ipsilesional M1. CONCLUSIONS: The results advocated the development of tailored digital rehabilitation strategies by combining the behavioral and cerebral hemodynamic data of patients with stroke. This approach aligns with the evolving paradigm of personalized rehabilitation in stroke recovery, highlighting the need for further extensive research to optimize rehabilitation outcomes.


Assuntos
Espectroscopia de Luz Próxima ao Infravermelho , Reabilitação do Acidente Vascular Cerebral , Extremidade Superior , Humanos , Masculino , Reabilitação do Acidente Vascular Cerebral/métodos , Idoso , Feminino , Extremidade Superior/fisiopatologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Estudos Transversais , Pessoa de Meia-Idade , Hemodinâmica/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem
2.
J Pers Med ; 14(6)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38929831

RESUMO

Many physical factors influence post-stroke functional outcomes. However, few studies have examined the influence of height on these outcomes. Here, data from the Korean Stroke Cohort for Functioning and Rehabilitation were used and patients' height was categorized into three groups: short (lower 25%), middle (middle 50%), and tall (upper 25%). Differences in the modified Rankin scale (mRS), functional ambulatory category (FAC), and Korean-translated version of the Modified Barthel Index (K-MBI) scores were analyzed for each group at 6 months post-stroke. A subgroup analysis was conducted based on the initial Fugl-Meyer Assessment (FMA) score. We analyzed functional outcomes in 5296 patients at 6 months post-stroke, adjusting for age and body mass index. The short-height group exhibited higher mRS scores (1.88 ± 0.043), lower FAC scores (3.74 ± 0.045), and lower K-MBI scores (82.83 ± 0.748) than the other height groups (p < 0.05). In the subgroup analysis, except for the very severe FMA group, the short-height group also exhibited worse outcomes in terms of mRS, FAC, and K-MBI scores (p < 0.05). Taken together, the short-height group exhibited worse outcomes related to disability, gait function, and ADLs at 6 months post-stroke.

3.
J Neurophysiol ; 132(1): 78-86, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691520

RESUMO

Stroke-caused synergies may result from the preferential use of the reticulospinal tract (RST) due to damage to the corticospinal tract. The RST branches multiple motoneuron pools across the arm together resulting in gross motor control or abnormal synergies, and accordingly, the controllability of individual muscles decreases. However, it is not clear whether muscles involuntarily activated by abnormal synergy vary depending on the muscles voluntarily activated when motor commands descend through the RST. Studies showed that abnormal synergies may originate from the merging and reweighting of synergies in individuals without neurological deficits. This leads to a hypothesis that those abnormal synergies are still selectively excited depending on the context. In this study, we test this hypothesis, leveraging the Fugl-Meyer assessment that could characterize the neuroanatomical architecture in individuals with a wide range of impairments. We examine the ability to perform an out-of-synergy movement with the flexion synergy caused by either shoulder or elbow loading. The results reveal that about 14% [8/57, 95% confidence interval (5.0%, 23.1%)] of the participants with severe impairment (total Fugl-Meyer score <29) in the chronic phase (6 months after stroke) are able to keep the elbow extended during shoulder loading and keep the shoulder at neutral during elbow loading. Those participants underwent a different course of neural reorganization, which enhanced abnormal synergies in comparison with individuals with mild impairment (P < 0.05). These results provide evidence that separate routes and synergy modules to motoneuron pools across the arm might exist even if the motor command is mediated possibly via the RST.NEW & NOTEWORTHY We demonstrate that abnormal synergies are still selectively excited depending on the context.


Assuntos
Músculo Esquelético , Tratos Piramidais , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/fisiopatologia , Músculo Esquelético/fisiologia , Músculo Esquelético/fisiopatologia , Tratos Piramidais/fisiopatologia , Tratos Piramidais/fisiologia , Idoso , Adulto , Cotovelo/fisiologia , Cotovelo/fisiopatologia , Ombro/fisiologia , Ombro/fisiopatologia
4.
J Neurophysiol ; 132(1): 87-95, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38748436

RESUMO

The flexion synergy and extension synergy are a representative consequence of a stroke and appear in the upper extremity and the lower extremity. Since the ipsilesional corticospinal tract (CST) is the most influential neural pathway for both extremities in motor execution, damage by a stroke to this tract could lead to similar motor pathological features (e.g., abnormal synergies) in both extremities. However, less attention has been paid to the interlimb correlations in the flexion synergy and extension synergy across different recovery phases of a stroke. We used results of the Fugl-Meyer assessment (FMA) to characterize those correlations in a total of 512 participants with hemiparesis after stroke from the acute phase to 1 year. The FMA provides indirect indicators of the degrees of the flexion synergy and extension synergy after stroke. We found that, generally, strong interlimb correlations (r > 0.65 with all P values < 0.0001) between the flexion synergy and extension synergy appeared in the acute-to-subacute phase (<90 days). However, the correlations of the lower-extremity extension synergy with the upper-extremity flexion synergy and extension synergy decreased (down to r = 0.38) 360 days after stroke (P < 0.05). These results suggest that the preferential use of alternative neural pathways after damage by a stroke to the CST enhances the interlimb correlations between the flexion synergy and extension synergy. At the same time, the results imply that the recovery of CST integrity or/and the fragmentation (remodeling) of the alternative neural substrates in the chronic phase may contribute to diversity in neural pathways in motor execution, eventually leading to reduced interlimb correlations.NEW & NOTEWORTHY For the first time, this article addresses the asynchronous relationships in the strengths of flexion and extension synergy expressions between the paretic upper extremity and lower extremity across various phases of stroke.


Assuntos
Extremidade Inferior , Paresia , Acidente Vascular Cerebral , Extremidade Superior , Humanos , Masculino , Acidente Vascular Cerebral/fisiopatologia , Feminino , Extremidade Superior/fisiopatologia , Pessoa de Meia-Idade , Idoso , Paresia/fisiopatologia , Paresia/etiologia , Extremidade Inferior/fisiopatologia , Tratos Piramidais/fisiopatologia , Adulto
5.
Healthcare (Basel) ; 12(7)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38610177

RESUMO

Nurses play a key role in providing integrated supportive care to cancer patients for their various needs. Efforts should be made to identify the competencies required for nurses providing integrated supportive care to cancer survivors, evaluate the competence level with reliable and reasonable tools, and continuously improve them. In Phase 1, the items of the scale were developed through a literature review and by conducting a focus group interview. In Phase 2, the validity and reliability of the scale were analyzed. A total of 504 nurses participated. Data were analyzed using item analysis, exploratory factor analysis, confirmatory factor analysis, Pearson's correlation with other scales, internal consistency, and split-half reliability. The developed scale consisted of 22 items. These items were grouped into five subscales and labeled as professionalism enhancement, care coordination, comprehensive nursing needs assessment, providing tailored information and education, and recurrence surveillance and secondary cancer prevention. Confirmatory factor analysis supported good convergent and discriminant validities. The criterion validity was verified. The internal consistency of the scale measured by Cronbach's α was 0.91. The developed scale is expected to be used as an instrument to identify cancer survivor integrated supportive care competencies of nurses in practice.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38683717

RESUMO

Robot-assisted motor training is applied for neurorehabilitation in stroke patients, using motor imagery (MI) as a representative paradigm of brain-computer interfaces to offer real-life assistance to individuals facing movement challenges. However, the effectiveness of training with MI may vary depending on the location of the stroke lesion, which should be considered. This paper introduces a multi-task electroencephalogram-based heterogeneous ensemble learning (MEEG-HEL) specifically designed for cross-subject training. In the proposed framework, common spatial patterns were used for feature extraction, and the features according to stroke lesions are shared and selected through sequential forward floating selection. The heterogeneous ensembles were used as classifiers. Nine patients with chronic ischemic stroke participated, engaging in MI and motor execution (ME) paradigms involving finger tapping. The classification criteria for the multi-task were established in two ways, taking into account the characteristics of stroke patients. In the cross-subject session, the first involved a direction recognition task for two-handed classification, achieving a performance of 0.7419 (±0.0811) in MI and 0.7061 (±0.1270) in ME. The second task focused on motor assessment for lesion location, resulting in a performance of 0.7457 (±0.1317) in MI and 0.6791 (±0.1253) in ME. Comparing the specific-subject session, except for ME on the motor assessment task, performance on both tasks was significantly higher than the cross-subject session. Furthermore, classification performance was similar to or statistically higher in cross-subject sessions compared to baseline models. The proposed MEEG-HEL holds promise in improving the practicality of neurorehabilitation in clinical settings and facilitating the detection of lesions.


Assuntos
Algoritmos , Interfaces Cérebro-Computador , Eletroencefalografia , Aprendizado de Máquina , Reabilitação do Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Eletroencefalografia/métodos , Reabilitação do Acidente Vascular Cerebral/métodos , Idoso , Imaginação/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/complicações , Robótica , Adulto , Desempenho Psicomotor , AVC Isquêmico/fisiopatologia , AVC Isquêmico/reabilitação , Imagens, Psicoterapia/métodos
7.
Medicina (Kaunas) ; 60(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38674206

RESUMO

Long-term changes in caregiver burden should be clarified considering that extended post-stroke disability can increase caregiver stress. We assessed long-term changes in caregiver burden severity and its predictors. This study was a retrospective analysis of the Korean Stroke Cohort for Functioning and Rehabilitation. Patients with an acute first-ever stroke were enrolled from August 2012 to May 2015. Data were collected at 6 months and 6 years after stroke onset. The caregiver burden was measured with a subjective caregiver burden questionnaire based on the Korean version of the Caregiver Burden Inventory. The caregivers' characteristics and patients' clinical and functional status were also examined at each follow-up. A high caregiver burden, which suggests a risk of burnout, was reported by 37.9% and 51.7% of caregivers at 6 months and 6 years post-stroke, respectively. Both the caregiver burden total score and proportion of caregivers at risk of burnout did not decrease between 6 months and 6 years. The patients' disability (OR = 11.60; 95% CI 1.58-85.08; p = 0.016), caregivers' self-rated stress (OR = 0.03; 95% CI 0.00-0.47; p = 0.013), and caregivers' quality of life (OR = 0.76; 95% CI 0.59-0.99; p = 0.042) were burden predictors at 6 months. At 6 years, only the patients' disability (OR = 5.88; 95% CI 2.19-15.82; p < 0.001) and caregivers' psychosocial stress (OR = 1.26; 95% CI 1.10-1.44; p = 0.001) showed significance. Nearly half of the caregivers were at risk of burnout, which lasted for 6 years after stroke onset. The patients' disability and caregivers' stress were burden predictors in both subacute and chronic phases of stroke. The findings suggest that consistent interventions, such as emotional support or counseling on stress relief strategies for caregivers of stroke survivors, may reduce caregiver burden. Further research is needed to establish specific strategies appropriate for Korean caregivers to alleviate their burden in caring for stroke patients.


Assuntos
Sobrecarga do Cuidador , Cuidadores , Qualidade de Vida , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/complicações , Estudos Retrospectivos , Cuidadores/psicologia , Cuidadores/estatística & dados numéricos , Idoso , Inquéritos e Questionários , República da Coreia , Qualidade de Vida/psicologia , Sobrecarga do Cuidador/psicologia , Sobreviventes/psicologia , Sobreviventes/estatística & dados numéricos , Adulto , Estresse Psicológico/psicologia , Estresse Psicológico/complicações , Estresse Psicológico/etiologia , Reabilitação do Acidente Vascular Cerebral/psicologia , Reabilitação do Acidente Vascular Cerebral/estatística & dados numéricos
8.
Phytopathology ; 114(5): 982-989, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38451552

RESUMO

Pine, an evergreen conifer, is widely distributed worldwide. It is economically, scientifically, and ecologically important. However, pine wilt disease (PWD) induced by the pine wood nematode (PWN) adversely affects pine trees. Many studies have been conducted on the PWN and its beetle vectors to prevent the spread of PWD. However, studies providing a comprehensive understanding of the pine tree transcriptome in response to PWN infection are lacking. Here, we performed temporal profiling of the pine tree transcriptome using PWD-infected red pine trees, Pinus densiflora, inoculated with the PWN by RNA sequencing. Our analysis revealed that defense-responsive genes involved in cell wall modification, jasmonic acid signaling, and phenylpropanoid-related processes were significantly enriched 2 weeks after PWD infection. Furthermore, some WRKY-type and MYB-type transcription factors were upregulated 2 weeks after PWD infection, suggesting that these transcription factors might be responsible for the genome-wide reprogramming of defense-responsive genes in the early PWD stage. Our comprehensive transcriptome analysis will assist in developing PWD-resistant pine trees and identifying genes to diagnose PWD at the early stage of infection, during which large-scale phenotypic changes are absent in PWD-infected pine trees.


Assuntos
Perfilação da Expressão Gênica , Pinus , Doenças das Plantas , Transcriptoma , Pinus/parasitologia , Pinus/genética , Animais , Doenças das Plantas/parasitologia , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
9.
Cell Rep Med ; 5(3): 101461, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38460517

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal types of cancer, and novel treatment regimens are direly needed. Epigenetic regulation contributes to the development of various cancer types, but its role in the development of and potential as a therapeutic target for PDAC remains underexplored. Here, we show that PRMT1 is highly expressed in murine and human pancreatic cancer and is essential for cancer cell proliferation and tumorigenesis. Deletion of PRMT1 delays pancreatic cancer development in a KRAS-dependent mouse model, and multi-omics analyses reveal that PRMT1 depletion leads to global changes in chromatin accessibility and transcription, resulting in reduced glycolysis and a decrease in tumorigenic capacity. Pharmacological inhibition of PRMT1 in combination with gemcitabine has a synergistic effect on pancreatic tumor growth in vitro and in vivo. Collectively, our findings implicate PRMT1 as a key regulator of pancreatic cancer development and a promising target for combination therapy.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Humanos , Camundongos , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Linhagem Celular Tumoral , Epigênese Genética , Gencitabina , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/uso terapêutico , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
10.
medRxiv ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38370652

RESUMO

Objective: The flexion synergy and extension synergy are a representative consequence of a stroke and appear in the upper extremity and lower extremity. Since the ipsilesional corticospinal tract (CST) is the most influential neural pathway for both extremities in motor execution, damage by a stroke to this tract could lead to similar motor pathological features (e.g., abnormal synergies) in both extremities. However less attention has been paid to the inter-limb correlations in the flexion synergy and extension synergy across different recovery phases of a stroke. Methods: In this study, we used results of the Fugl-Meyer assessment (FMA) to characterize those correlations in a total of 512 participants with hemiparesis post stroke from the acute phase to 1 year. The FMA provides indirect indicators of the degrees of the flexion synergy and extension synergy post stroke. Results: We found that generally, strong inter-limb correlations (r>0.65 with all p-values<0.0001) between the flexion synergy and extension synergy appeared in the acute-to-subacute phase (<90 days). But correlations of lower-extremity extension synergy with upper-extremity flexion synergy and extension synergy decreased (down to r=0.38) around 360 days after stroke (p<0.05). Interpretation: These results suggest that the preferential use of alternative neural pathways after damage by a stroke to the CST enhances inter-limb correlations between the flexion synergy and extension, however a recovery of the CST or/and the functional fragmentation (remodeling) of the alternative neural substrates in the chronic phase contribute to diversity in neural pathways in motor execution, eventually leading to reduced inter-limb correlations.

11.
Sci Rep ; 14(1): 4483, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38396060

RESUMO

This study investigates whether simultaneous high-definition transcranial direct current stimulation (HD-tDCS) enhances the effects of robot-assisted gait training in stroke patients. Twenty-four participants were randomly allocated to either the robot-assisted gait training with real HD-tDCS group (real HD-tDCS group) or robot-assisted gait training with sham HD-tDCS group (sham HD-tDCS group). Over four weeks, both groups completed 10 sessions. The 10 Meter Walk Test, Timed Up and Go, Functional Ambulation Category, Functional Reach Test, Berg Balance Scale, Dynamic Gait Index, Fugl-Meyer Assessment, and Korean version of the Modified Barthel Index were conducted before, immediately after, and one month after the intervention. The real HD-tDCS group showed significant improvements in the 10 Meter Walk Test, Timed Up and Go, Functional Reach Test, and Berg Balance Scale immediately and one month after the intervention, compared with before the intervention. Significant improvements in the Dynamic Gait Index and Fugl-Meyer Assessment were also observed immediately after the intervention. The sham HD-tDCS group showed no significant improvements in any of the tests. Application of HD-tDCS during robot-assisted gait training has a positive effect on gait and physical function in chronic stroke patients, ensuring long-term training effects. Our results suggest the effectiveness of HD-tDCS as a complementary tool to enhance robotic gait rehabilitation therapy in chronic stroke patients.


Assuntos
Robótica , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Robótica/métodos , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/terapia , Marcha/fisiologia , Resultado do Tratamento
12.
J Am Heart Assoc ; 13(4): e032377, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38348806

RESUMO

BACKGROUND: Information on the long-term prognosis in patients with isolated thalamic stroke is sparse. We report the functional outcomes of patients with thalamic stroke up to 24 months from the KOSCO (Korean Stroke Cohort for Functioning and Rehabilitation) study. METHODS AND RESULTS: Isolated thalamic stroke was defined as the presence of lesions solely in the thalamus, excluding cases with lesions in other brain parenchyma areas apart from the thalamus, as identified by brain magnetic resonance imaging or computed tomography scans. The Fugl-Meyer Assessment, the Functional Ambulatory Category, the Korean Mini-Mental State Examination, the American Speech-Language-Hearing Association National Outcome Measurement System Swallowing Scale, and the short version of the Korean Frenchay Aphasia Screening Test were used to assess physical impairment. The Functional Independence Measure and modified Rankin Scale were used to assess functional outcomes. All measurements were conducted up to 24 months poststroke. A total of 297 patients were included, consisting of 235 with ischemic and 62 with hemorrhagic stroke. Except for the Functional Ambulatory Category and Functional Independence Measure, all physical impairments showed significant improvement up to 3 months poststroke (P<0.001) and reached a plateau. The Functional Ambulatory Category and Functional Independence Measure scores continued to improve up to 12 months poststroke (P<0.05) and reached a plateau. At 7 days poststroke, 47.5% of patients had no disability (modified Rankin Scale score<2), whereas at 24 months poststroke, 76.4% of patients had no significant disability. CONCLUSIONS: Patients showed rapid recovery from physical impairment up to 3 months poststroke, with additional improvements in ambulatory function and independence observed up to 12 months poststroke. Additionally, relatively favorable long-term functional prognosis at 24 months after onset was demonstrated. These results could provide insights into the proper management regarding functional outcomes of patients with isolated thalamic stroke.


Assuntos
Acidente Vascular Cerebral Hemorrágico , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Prognóstico , Imageamento por Ressonância Magnética , Recuperação de Função Fisiológica
13.
Cancer Sci ; 115(4): 1283-1295, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38348576

RESUMO

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in circulating tumor deoxyribonucleic acid (ctDNA) have been reported as representative noninvasive prognostic markers for pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to evaluate single KRAS mutations as prognostic and predictive biomarkers, with an emphasis on potential therapeutic approaches to PDAC. A total of 128 patients were analyzed for multiple or single KRAS mutations (G12A, G12C, G12D, G12R, G12S, G12V, and G13D) in their tumors and plasma using droplet digital polymerase chain reaction (ddPCR). Overall, KRAS mutations were detected by multiplex ddPCR in 119 (93%) of tumor DNA and 68 (53.1%) of ctDNA, with a concordance rate of 80% between plasma ctDNA and tumor DNA in the metastatic stage, which was higher than the 44% in the resectable stage. Moreover, the prognostic prediction of both overall survival (OS) and progression-free survival (PFS) was more relevant using plasma ctDNA than tumor DNA. Further, we evaluated the selective tumor-suppressive efficacy of the KRAS G12C inhibitor sotorasib in a patient-derived organoid (PDO) from a KRAS G12C-mutated patient using a patient-derived xenograft (PDX) model. Sotorasib showed selective inhibition in vitro and in vivo with altered tumor microenvironment, including fibroblasts and macrophages. Collectively, screening for KRAS single mutations in plasma ctDNA and the use of preclinical models of PDO and PDX with genetic mutations would impact precision medicine in the context of PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Biomarcadores Tumorais/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/diagnóstico , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , DNA de Neoplasias/genética , Mutação , Microambiente Tumoral
14.
Tob Induc Dis ; 222024.
Artigo em Inglês | MEDLINE | ID: mdl-38333885

RESUMO

INTRODUCTION: The study aimed to identify predictors associated with long-term tobacco cessation at 12-month follow-up among users of the National Smoking Cessation Services (NSCS) in Korea. METHODS: To measure the long-term effect of NSCS delivery, the target sample size of 5167 adult smokers registered in the NSCS in 2018 was enrolled with proportional random sampling. A multiple logistic regression analysis (crude, adjusted) was performed to identify the changes in smoking status at the 12-month follow-up after the last NSCS enrollment and the potential factors associated with changes in smoking status. RESULTS: The response rate to reach the number of subjects targeted was 22.4%. A total of 41.2% of the tobacco users enrolled had successfully quit at baseline, and the 7-day point prevalence of tobacco cessation at the follow-up at 12 months, via a telephone survey, was 34.4%. Factors positively associated with cessation at the 12-month follow-up were longer experience with tobacco abstinence and additional quitting attempts with or without NSCS enrollment, although every additional quit attempt with NSCS use had a better outcome. In addition, having a successful quit outcome with NSCS use at the baseline and having more satisfaction with the service of professional counseling or incentives than others provided by NSCS, increased cessation at follow-up after adjustment of other factors considered. CONCLUSIONS: In addition to multiple quitting attempts, longer experience with tobacco abstinence, and additional enrollment in NSCS, the service experience, and satisfaction with the content that NSCS offered, might improve the lasting success of abstinence. These results might be considered to improve the contents and protocols of the NSCS for better outcomes.

15.
J Proteome Res ; 23(3): 905-915, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38293943

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis due to the absence of diagnostic markers and molecular targets. Here, we took an unconventional approach to identify new molecular targets for pancreatic cancer. We chose uncharacterized protein evidence level 1 without function annotation from extensive proteomic research on pancreatic cancer and focused on proline and serine-rich 2 (PROSER2), which ranked high in the cell membrane and cytoplasm. In our study using cell lines and patient-derived orthotopic xenograft cells, PROSER2 exhibited a higher expression in cells derived from primary tumors than in those from metastatic tissues. PROSER2 was localized in the cell membrane and cytosol by immunocytochemistry. PROSER2 overexpression significantly reduced the metastatic ability of cancer cells, whereas its suppression had the opposite effect. Proteomic analysis revealed that PROSER2 interacts with STK25 and PDCD10, and their binding was confirmed by immunoprecipitation and immunocytochemistry. STK25 knockdown enhanced metastasis by decreasing p-AMPK levels, whereas PROSER2-overexpressing cells increased the level of p-AMPK, indicating that PROSER2 suppresses invasion via the AMPK pathway by interacting with STK25. This is the first demonstration of the novel role of PROSER2 in antagonizing tumor progression via the STK25-AMPK pathway in PDAC. LC-MS/MS data are available at MassIVE (MSV000092953) and ProteomeXchange (PXD045646).


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Humanos , Proteínas Quinases Ativadas por AMP , Cromatografia Líquida , Proteômica , Proliferação de Células , Movimento Celular , Espectrometria de Massas em Tandem , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/genética , Modelos Animais de Doenças , Proteínas Serina-Treonina Quinases , Peptídeos e Proteínas de Sinalização Intracelular
16.
Am J Phys Med Rehabil ; 103(4): 325-332, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37903631

RESUMO

OBJECTIVE: This study aimed to demonstrate the incidence of altered level of consciousness after hemorrhagic stroke and identify factors associated with altered level of consciousness at 3 mos after stroke. DESIGN: This study used data from a prospective multicenter cohort study conducted in nine hospitals in Korea and included 1677 patients with first-ever hemorrhagic stroke. Patients were dichotomized into those with and without altered level of consciousness at 3 mos after stroke. Multivariate logistic regression analysis was performed to identify factors associated with subacute to chronic stage altered level of consciousness. RESULTS: Among patients with hemorrhagic stroke (age: 20-99 yrs, female 50.21%), the prevalence of altered level of consciousness at admission was 38.58% (25.4% [drowsy], 6.38% [stupor], and 6.8% [coma]) and 17.29% 3 mos after stroke. Multivariate logistic regression analysis revealed that independent factors associated with altered level of consciousness at 3 mos after stroke included late seizure (odds ratio [95% confidence interval], 5.93 [1.78-20.00]), stroke progression (3.84 [1.48-9.64]), craniectomy (2.19 [1.19-4.00]), history of complications (1.74 [1.18-2.55]), age at stroke onset (1.08 [1.07-1.10]), and initial Glasgow Coma Scale score category (0.36 [0.30-0.44]). CONCLUSIONS: The factors associated with altered level of consciousness at 3 mos after stroke should be considered when explaining long-term consciousness status and focused management of modifiable factors in acute care hospitals could help ameliorate altered level of consciousness and promote recovery after stroke.


Assuntos
Acidente Vascular Cerebral Hemorrágico , Acidente Vascular Cerebral , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Estudos de Coortes , Estado de Consciência , Transtornos da Consciência/epidemiologia , Transtornos da Consciência/etiologia , Escala de Coma de Glasgow , Incidência , Estudos Prospectivos , República da Coreia/epidemiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia
17.
Genes (Basel) ; 14(11)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38003017

RESUMO

M. incognita, a root-knot nematode (RKN), infects the roots of several important food crops, including sweet potato (Ipomoea batatas Lam.), and severely reduces yields. However, the molecular mechanisms underlying infection remain unclear. Previously, we investigated differential responses to RKN invasion in susceptible and resistant sweet potato cultivars through RNA-seq-based transcriptome analysis. In this study, gene expression similarities and differences were examined in RKN-susceptible sweet potato cultivars during the compatible response to RKN infection. Three susceptible cultivars investigated in previous research were used: Dahomi (DHM), Shinhwangmi (SHM), and Yulmi (YM). Of the three cultivars, YM had the highest number of genes with altered expression in response to infection. YM was also the cultivar with the highest susceptibility to RKN. Comparisons among cultivars identified genes that were regulated in more than one cultivar upon infection. Pairwise comparisons revealed that YM and DHM shared the most regulated genes, whereas YM and SHM shared the lowest number of regulated genes. Five genes were up-regulated, and two were down-regulated, in all three cultivars. Among these, four genes were highly up-regulated in all cultivars: germin-like protein, anthranilate synthase α subunit, isocitrate lyase, and uncharacterized protein. Genes were also identified that were uniquely regulated in each cultivar in response to infection, suggesting that susceptible cultivars respond to infection through shared and cultivar-specific pathways. Our findings expand the understanding of the compatible response to RKN invasion in sweet potato roots and provide useful information for further research on RKN defense mechanisms.


Assuntos
Ipomoea batatas , Infecções por Nematoides , Tylenchoidea , Animais , Transcriptoma/genética , Ipomoea batatas/genética , Tylenchoidea/genética , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Doenças das Plantas/genética , Perfilação da Expressão Gênica
18.
Transplant Proc ; 55(9): 2143-2158, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37867003

RESUMO

BACKGROUND: Although liver transplantation (LT) is one of the definitive treatments for patients with end-stage liver failure, it inevitably results in ischemic reperfusion injury. It is known that prognosis is improved when temporary ischemic conditioning (IC) is applied to patients with ischemic reperfusion injury. The objective of this meta-analysis was to determine the short-term and long-term effects of IC on the clinical outcomes of LT recipients. METHODS: Randomized controlled studies on IC in patients with LTs were included. Patients were compared between an IC group and a sham group. Studies were retrieved from PubMed, Embase, and Cochrane Library. The risk of bias was evaluated using RoB 2.0. Mortality, graft function, and major complications were synthesized using RevMan 5.4.1. RESULTS: Among 316 papers, 17 articles (1196 patients) were included. There was an insignificant increase in short-term mortality (risk ratio [RR]: 3.00, 95% CI: 0.32-28.14, P = .34). However, long-term mortality was lower in the IC group than in the sham group, but not significantly (RR: 0.75; 95% CI: 0.47-1.20, P = .23). Short-term graft function (acute graft rejection and primary graft non-function) was not improved by IC. One-year graft loss tended to show better results in the IC group (RR: 0.53, 95% CI: 0.26-1.07, P = .08). CONCLUSION: Ischemic conditioning did not have a beneficial effect on LT. Although long-term outcomes appear to be better in the IC group than in the sham group, further randomized controlled trials are needed.


Assuntos
Transplante de Fígado , Traumatismo por Reperfusão , Humanos , Transplante de Fígado/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/prevenção & controle
19.
Exp Mol Med ; 55(10): 2127-2137, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37779144

RESUMO

Recent discoveries in stem cell and developmental biology have introduced a new era marked by the generation of in vitro models that recapitulate early mammalian development, providing unprecedented opportunities for extensive research in embryogenesis. Here, we present an overview of current techniques that model early mammalian embryogenesis, specifically noting models created from stem cells derived from two significant species: Homo sapiens, for its high relevance, and Mus musculus, a historically common and technically advanced model organism. We aim to provide a holistic understanding of these in vitro models by tracing the historical background of the progress made in stem cell biology and discussing the fundamental underlying principles. At each developmental stage, we present corresponding in vitro models that recapitulate the in vivo embryo and further discuss how these models may be used to model diseases. Through a discussion of these models as well as their potential applications and future challenges, we hope to demonstrate how these innovative advances in stem cell research may be further developed to actualize a model to be used in clinical practice.


Assuntos
Embrião de Mamíferos , Células-Tronco , Humanos , Animais , Camundongos , Desenvolvimento Embrionário , Biologia do Desenvolvimento , Mamíferos
20.
Medicina (Kaunas) ; 59(10)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37893569

RESUMO

Background and Objectives: Patients recovering from mild coronavirus disease (COVID-19) reportedly have dysphagia or difficulty in swallowing. We compared the prevalence of dysphagia between patients diagnosed with mild COVID-19 and those diagnosed with aspiration pneumonia alone. Materials and Methods: A retrospective study was conducted from January 2020 to June 2023 in 160 patients referred for a videofluoroscopic swallowing study (VFSS) to assess for dysphagia. The cohort included 24 patients with mild COVID-19 and aspiration pneumonia, 30 with mild COVID-19 without aspiration pneumonia, and 106 with aspiration pneumonia alone. We reviewed the demographic data, comorbidities, and VFSS results using the penetration-aspiration scale (PAS) and functional dysphagia scale (FDS). Results: In a study comparing patients with mild COVID-19 (Group A) and those with aspiration pneumonia alone (Group B), no significant differences were observed in the baseline characteristics, including the prevalence of dysphagia-related comorbidities between the groups. Group A showed milder dysphagia, as evidenced by lower PAS and FDS scores, shorter oral and pharyngeal transit times (p = 0.001 and p = 0.003, respectively), and fewer residues in the vallecula and pyriform sinuses (p < 0.001 and p < 0.03, respectively). When Group A was subdivided into those with COVID-19 with (Group A1) and without aspiration pneumonia (Group A2), both subgroups outperformed Group B in terms of specific VFSS metrics, such as oral transit time (p = 0.01), pharyngeal transit time (p = 0.04 and p = 0.02, respectively), and residue in the vallecula (p = 0.04 and p = 0.02, respectively). However, Group B showed improved triggering of the pharyngeal swallowing reflex compared with Group A2 (p = 0.02). Conclusion: Mild COVID-19 patients showed less severe dysphagia than those with aspiration pneumonia alone. This finding was consistent across VFSS parameters, even when the COVID-19 group was subdivided based on the status of aspiration pneumonia.


Assuntos
COVID-19 , Transtornos de Deglutição , Pneumonia Aspirativa , Humanos , Transtornos de Deglutição/diagnóstico por imagem , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Deglutição , Estudos Retrospectivos , Prevalência , COVID-19/complicações , COVID-19/epidemiologia , Pneumonia Aspirativa/epidemiologia , Pneumonia Aspirativa/etiologia
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