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1.
Theranostics ; 12(8): 3676-3689, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35664056

RESUMO

Understanding cancer heterogeneity is essential to finding diverse genetic mutations in metastatic cancers. Thus, it is critical to isolate all types of CTCs to identify accurate cancer information from patients. Moreover, full automation robustly capturing the full spectrum of CTCs is an urgent need for CTC diagnosis to be routine clinical practice. Methods: Here we report the full capture of heterogeneous CTC populations using fully automated, negative depletion-based continuous centrifugal microfluidics (CCM). Results: The CCM system demonstrated high performance (recovery rates exceeding 90% and WBC depletion rate of 99.9%) across a wide range of phenotypes (EpCAM(+), EpCAM(-), small-, large-sized, and cluster) and cancers (lung, breast, and bladder). Applied in 30 lung adenocarcinoma patients harboring epidermal growth factor receptor (EGFR) mutations, the system isolated diverse phenotypes of CTCs in marker expression and size, implying the importance of unbiased isolation. Genetic analyses of intra-patient samples comparing cell-free DNA with CCM-isolated CTCs yielded perfect concordance, and CTC enumeration using our technique was correlated with clinical progression as well as response to EGFR inhibitors. Conclusion: Our system also introduces technical advances which assure rapid, reliable, and reproducible results, thus enabling a more comprehensive application of robust CTC analysis in clinical practice.


Assuntos
Células Neoplásicas Circulantes , Automação , Linhagem Celular Tumoral , Separação Celular/métodos , Molécula de Adesão da Célula Epitelial/genética , Receptores ErbB/genética , Humanos , Microfluídica/métodos , Células Neoplásicas Circulantes/metabolismo
2.
Stroke ; : 101161STROKEAHA121038196, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35713003

RESUMO

BACKGROUND: We aimed to verify the validity of the proportional recovery model for the lower extremity. METHODS: We reviewed clinical data of patients enrolled in the Korean Stroke Cohort for Functioning and Rehabilitation between August 2012 and May 2015. Recovery proportion was calculated as the amount of motor recovery over initial motor impairment, measured as the Fugl-Meyer Assessment of Lower Extremity score. We used the logistic regression method to model the probability of achieving the full Fugl-Meyer Assessment of Lower Extremity score, whereby we considered the ceiling effect of the score. To show the difference in the prevalence of achieving the full Fugl-Meyer Assessment of Lower Extremity score between 3 and 6 months poststroke, we constructed a marginal model through the generalized estimating equation method. We also performed the propensity score matching analysis to show the dependency of recovery proportion on the initial motor deficit at 3 and 6 months poststroke. RESULTS: We evaluated 1085 patients. The recovery proportions at 3 and 6 months poststroke were 0.67±0.42 and 0.75±0.39, respectively. A 1-unit decrease in the initial neurological impairment and the age at stroke onset increased the probability of achieving the full Fugl-Meyer Assessment of Lower Extremity score, which occurred at both 3 and 6 months poststroke. The prevalence of those who reach full lower limb motor recovery differs significantly between 3 and 6 months poststroke. We also found out that the recovery proportion at both 3 and 6 months poststroke is determined by the initial motor deficits of the lower limb. These results are not consistent with the proportional recovery model. CONCLUSIONS: Our results demonstrated that the proportional recovery model for the lower limb is invalid.

3.
Life (Basel) ; 12(4)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35454994

RESUMO

Membrane-free stem cell extract (MFSCE) of human adipose tissues possesses various biological activities. However, the effects of MFSCE on blood-brain barrier dysfunction and brain damage are unknown. In this study, we determined the role of MFSCE in an ischemic stroke mouse model. Mice were treated with MFSCE once daily for 4 days and 1 h before ischemic damage. Experimental ischemia was induced by photothrombosis. Pretreatment with MFSCE reduced infarct volume and edema and improved neurological, as well as motor functions. Evans blue leakage and water content in the brain tissue were reduced by MFSCE pretreatment relative to those in the vehicle group. MFSCE increased the expression of the tight junction proteins zonula occludens 1 and claudin-5, as well as vascular endothelial-cadherin, but decreased that of matrix metalloproteinase 9. Notably, MFSCE treatment decreased cell death and the level of NOD-like receptor protein 3 inflammasome, consistent with the downregulated expression of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-18 in the ischemic brain. These effects might have occurred via the suppression of the expression of Toll-like receptor 4 and activation of nuclear factor-κB. The results highlighted the potential of MFSCE treatment as a novel and preventive strategy for patients at a high risk of ischemic stroke.

4.
J Pers Med ; 12(3)2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35330389

RESUMO

BACKGROUND: This study investigated the impact of post-stroke depression (PSD) on cognitive aging in elderly stroke patients. METHODS: This study was an interim analysis of the Korean Stroke Cohort for Functioning and Rehabilitation. Among 10,636 patients with first-ever stroke, a total of 3215 patients with normal cognitive function three months post-stroke were included in the analysis. PSD was defined using the Korean Geriatric Depression Scale Short Form (K-GDS-SF) at three months. Cognitive aging was defined as a decline in the Korean version of the Mini-Mental Status Examination (K-MMSE) score to less than the second percentile. RESULTS: The hazard ratio (HR) of PSD for cognitive decline was 2.16 (95% CI, 1.34-3.50, p < 0.01) in the older group (age ≥65 years), and 1.02 (95% CI, 0.50-2.07, n.s.) in the younger group (age <65 years). When the older group was divided by sex, the HR was 2.50 (95% CI, 1.26-4.96, p < 0.01) in male patients and 1.80 (95% CI, 0.93-3.51, n.s.) in female patients. However, women showed a higher incidence of cognitive decline in both the PSD and no PSD groups. Among K-GDS-SF factors, "Negative judgment about the past, present, and future" increased the HR of PSD in older male patients. CONCLUSIONS: Early PSD increased the HR for cognitive decline in older stroke patients, mainly in males. Specifically, older male patients with negative thinking were at increased risk of cognitive decline. The findings also suggest that older women may be at risk for cognitive decline. Therefore, preventive interventions for cognitive decline should be tailored differently for men and women.

5.
Adv Sci (Weinh) ; 9(11): e2104629, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35076161

RESUMO

Photobiomodulation (PBM) has received attention due to its potential for improving tissue function and enhancing regeneration in stroke. A lightweight, compact, and simple system of miniaturized electronic devices consisting of packaged light-emitting diodes (LEDs) that incorporates a flexible substrate for in vivo brain PBM in a mouse model is developed. Using this device platform, the preventive and therapeutic effects of PBM affixed to the exposed skull of mice in the photothrombosis and middle cerebral artery occlusion stroke model are evaluated. Among the wavelength range of 630, 850, and 940 nm LED array, the PBM with 630-nm LED array is proved to be the most effective for reducing the infarction volume and neurological impairment after ischemic stroke. Moreover, the PBM with 630 nm LED array remarkably improves the capability of spatial learning and memory in the chronic poststroke phase, attenuates AIM2 inflammasome activation and inflammasome-mediated pyroptosis, and modulates microglial polarization in the hippocampus and cortex 7 days following ischemic stroke. Thus, PBM may prevent tissue and functional damage in acute ischemic injury, thereby attenuating the development of cognitive impairment after stroke.


Assuntos
AVC Isquêmico , Terapia com Luz de Baixa Intensidade , Acidente Vascular Cerebral , Animais , Inflamassomos , Camundongos , Crânio
6.
Front Neurol ; 13: 755316, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370909

RESUMO

Objective: To investigate the available evidence on early supported discharge (ESD) and transitional care (TC) delivery service in patients with cerebrovascular disease. Methods: A systematic literature search was conducted to collect all available evidence on the use of ESD and TC services. We included cluster-randomized pragmatic trials or randomized controlled trials (RCTs) that recruited patients with stroke or transient ischemic attack to receive either conventional care or any care service intervention that included rehabilitation or support provided by professional medical personnel with the aim of accelerating and supporting home discharge. Relevant data were electronically searched through international databases (Cochrane Library, EMBASE, and PubMed) and incorporated into a summary grid to investigate research outcomes and provide a narrative synthesis. Furthermore, we compared the outcomes in terms of length of hospital stay, patient and caregiver outcomes, and mortality through meta-analysis. Results: We identified and included a total of 20 publications of various original randomized studies. There were 18 studies conducted in western countries and 2 in eastern countries. The meta-analysis revealed a tendency that ESD or TC could decrease the length of hospital stay more than the usual care [standardized mean difference (SMD) -0.13; 95% confidence interval (CI) -0.31 to 0.04 days; P = 0.14]. Moreover, there was a tendency that ESD resulted in better activities of daily living (ADL) than usual care (SMD 0.29; 95% CI -0.04 to 0.61; P = 0.08). Patient outcome based on modified Rankin scale (mRS) score (SMD -0.11; 95% CI -0.38 to 0.17; P = 0.45] and mortality (odds ratio 0.80; 95% CI 0.56-1.17; P = 0.25) did not reveal any significant difference. The Caregiver Strain Index revealed no difference. Conclusion: We did not find a large effect size for the use of TC and ESD. When implementing the TC and ESD model from western to Asian countries, services should be prepared and implemented in accordance with national medical rehabilitation pathways for cerebrovascular disease.

7.
J Pers Med ; 11(11)2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34834503

RESUMO

One of the pathophysiologies of post-stroke spasticity (PSS) is the imbalance of the reticulospinal tract (RST) caused by injury to the corticoreticular pathway (CRP) after stroke. We investigated the relationship between injuries of the CRP and PSS using MR diffusion tensor imaging (DTI). The subjects were divided into spasticity and control groups. We measured the ipsilesional fractional anisotropy (iFA) and contralesional fractional anisotropy (cFA) values on the reticular formation (RF) of the CRP were on the DTI images. We carried out a retrospective analysis of 70 patients with ischemic stroke. The cFA values of CRP in the spasticity group were lower than those in the control group (p = 0.04). In the sub-ROI analysis of CRP, the iFA values of pontine RF were lower than the cFA values in both groups (p < 0.05). The cFA values of medullary RF in the spasticity group were lower than the iFA values within groups, and also lower than the cFA values in the control group (p < 0.05). This results showed the CRP injury and that imbalance of RST caused by CRP injury was associated with PSS. DTI analysis of CRP could provide imaging evidence for the pathophysiology of PSS.

8.
Ann Rehabil Med ; 45(5): 359-367, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34743479

RESUMO

OBJECTIVE: To investigate long-term and serial functional outcomes in ischemic stroke patients without diabetes with post-stroke hyperglycemia. METHODS: The Korean Stroke Cohort for Functioning and Rehabilitation (KOSCO) is a large, multi-center, prospective cohort study of stroke patients admitted to participating hospitals in nine areas of Korea. From KOSCO, ischemic stroke patients without diabetes were recruited and divided into two groups: patients without diabetes without (n=779) and with post-stroke hyperglycemia (n=223). Post-stroke hyperglycemia was defined as a glucose level >8 mmol/L. Functional assessments were performed 7 days and 3, 6, and 12 months after stroke onset. RESULTS: There were no significant differences in baseline characteristics between the groups, except in the age of onset and smoking. Analysis of the linear correlation between the initial National Institutes of Health Stroke Scale (NIHSS) score and glucose level showed no significant difference. Among our functional assessments, NIHSS, Fugl-Meyer Assessment (affected side), Functional Ambulatory Category, modified Rankin Scale, and Korean Mini-Mental State Examination (K-MMSE) showed statistically significant improvements in each group. All functional improvements except K-MMSE were significantly higher in patients without post-stroke hyperglycemia at 7 days and 3, 6, and 12 months. CONCLUSION: The glucose level of ischemic stroke patients without diabetes had no significant correlation with the initial NIHSS score. The long-term effects of stress hyperglycemia showed worse functional outcomes in ischemic stroke patients without diabetes with post-stroke hyperglycemia.

9.
PLoS One ; 16(10): e0258479, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34648529

RESUMO

OBJECTIVE: To investigate the effects of axial length (AL) on the peripapillary microvascular density acquired from optical coherence tomography angiography (OCTA). METHODS: Retrospective observational study. A total of 111 eyes from 111 normal healthy subjects were examined. The subjects were divided into three groups according to the AL: Group 1 (AL: < 24.0 mm; 35 eyes), Group 2 (AL: 24.0-25.99 mm; 37 eyes), and Group 3 (AL: ≥ 26 mm; 39 eyes). Peripapillary OCTA images were acquired using 6× 6 mm angiography scans, and vessel density (VD) and perfusion density (PD) of the superficial capillary plexus were calculated automatically. VD and PD were compared among the three groups according to the distance from the optic disc (inner and outer rings). Linear regression analyses were also performed to identify clinical factors associated with average VD. RESULTS: The average ALs of Groups 1-3 were 23.33± 0.57, 25.05± 0.60, and 27.42± 0.82, respectively. Average VD (P = 0.009) and PD (P = 0.029) in the inner ring increased with increasing AL. However, average VD (P < 0.001) and PD (P < 0.001) in the outer ring decreased with AL increased; the same trends were found for the full areas (VD, p<0.001; PD, p = 0.001). Average VDs in the inner and outer rings were not associated (P = 0.938). CONCLUSIONS: Peripapillary VD and PD were significantly associated with AL. Depending on the distance from the disc, peripapillary VDs and PDs of the inner and outer rings were differentially affected by AL. Physicians should therefore consider the effects of AL in the analyses of peripapillary microvasculature.


Assuntos
Microvasos/fisiologia , Tomografia de Coerência Óptica/métodos , Adulto , Estudos de Casos e Controles , Feminino , Angiofluoresceinografia , Humanos , Modelos Lineares , Masculino , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Disco Óptico/fisiologia , Estudos Retrospectivos
10.
Front Neurol ; 12: 710640, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566853

RESUMO

Introduction: Early supported discharge (ESD) is a transitional care model aimed at facilitating post-acute stroke patients' discharge to home. Previous studies have demonstrated that ESD provides equivalent patient and caregiver outcomes with superior cost-effectiveness compared to conventional rehabilitation (CR). This study intends to examine the feasibility of ESD in Korea. Methods and Analysis: This study is designed as a multicenter assessor-blinded, randomized controlled trial. Ninety post-acute stroke patients with mild to moderate disability (modified Rankin Scale 1-3) will be recruited from three university hospitals (30 patients per hospital) in Korea and allocated to either the ESD group or the CR group in a 1:1 ratio. Patients in the ESD group will receive individualized discharge planning and goal setting, a 4-week home-based rehabilitation program, and liaison service to community-based resources by a multidisciplinary team. Patients in the CR group will receive rehabilitation practices according to their current hospital policy. Outcomes: The primary outcome is the Korean version of the modified Barthel Index, and the primary endpoint was post-onset 3 months. Clinical outcomes, patient/caregiver reported outcomes, and socioeconomic outcomes will be measured at baseline, 1 month after discharge, 2 months after discharge, and 3 months after onset. Discussion: The efficacy and cost-effectiveness of ESD can vary according to the healthcare system and sociocultural aspects. To establish ESD as an alternative transitional care model for post-acute stroke patients in Korea, its feasibility needs to be examined in prior. This study will add evidence on the applicability of ESD in Korea. Ethical Considerations: The study protocol was reviewed and approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB number B-2012/654-308). The study protocol was registered at ClinicalTrials.gov (Identifier NCT04720820). Disseminations will include submission to peer-reviewed journals and presentations at conferences.

11.
J Alzheimers Dis ; 83(4): 1513-1519, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34420956

RESUMO

BACKGROUND: Photobiomodulation (PBM) affects local blood flow regulation through nitric oxide generation, and various studies have reported on its effect on improving cognitive function in neurodegenerative diseases. However, the effect of PBM in the areas of the vertebral arteries (VA) and internal carotid arteries (ICA), which are the major blood-supplying arteries to the brain, has not been previously investigated. OBJECTIVE: We aimed to determine whether irradiating PBM in the areas of the VA and ICA, which are the major blood-supplying arteries to the brain, improved regional cerebral blood flow (rCBF) and cognitive function. METHODS: Fourteen patients with mild cognitive impairments were treated with PBM. Cognitive assessment and single-photon emission computed tomography were implemented at the baseline and at the end of PBM. RESULTS: Regarding rCBF, statistically significant trends were found in the medial prefrontal cortex, lateral prefrontal cortex, anterior cingulate cortex, and occipital lateral cortex. Based on the cognitive assessments, statistically significant trends were found in overall cognitive function, memory, and frontal/executive function. CONCLUSION: We confirmed the possibility that PBM treatment in the VA and ICA areas could positively affect cognitive function by increasing rCBF. A study with a larger sample size is needed to validate the potential of PBM.


Assuntos
Encéfalo/efeitos da radiação , Circulação Cerebrovascular/efeitos da radiação , Cognição/efeitos da radiação , Disfunção Cognitiva/terapia , Terapia com Luz de Baixa Intensidade , Idoso , Artéria Carótida Interna/efeitos da radiação , Função Executiva/efeitos da radiação , Feminino , Humanos , Masculino , Memória/efeitos da radiação , Pessoa de Meia-Idade , Testes Neuropsicológicos , Projetos Piloto , Fluxo Sanguíneo Regional , Tomografia Computadorizada de Emissão de Fóton Único
12.
Arch Phys Med Rehabil ; 102(12): 2343-2352.e3, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34348122

RESUMO

OBJECTIVE: To identify the incidence of dysphagia after ischemic stroke and determine factors affecting the presence of dysphagia. DESIGN: Retrospective case-control study. This was an interim analysis of a prospective multicenter Korean stroke cohort. SETTING: Acute care university hospitals. PARTICIPANTS: Patients (N=6000) with first-ever acute ischemic stroke. Patients were divided into 2 groups according to the presence or absence of dysphagia confirmed at 7 days after onset using the American Speech-Language-Hearing Association National Outcomes Measurement System (ASHA-NOMS) scale, which was determined after conducting screening or standardized tests. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Age at stroke onset, body mass index (BMI), premorbid modified Rankin Scale (mRS), brainstem lesions, National Institutes of Health Stroke Scale (NIHSS), poststroke mRS, and ASHA-NOMS swallowing level at poststroke day 7 were evaluated. RESULTS: Among patients with ischemic stroke, 32.3% (n=1940) had dysphagia at 7 days after stroke onset. At discharge, 80.5% (n=1561) still had dysphagia. The prediction model for the presence of dysphagia identified age at onset, underweight (BMI <18.5 kg/m2), premorbid mRS, brainstem lesions, and NIHSS as independent predictors. The odds ratio (OR) for the presence of dysphagia significantly increased with underweight (OR, 1.6684; 95% confidence interval [CI], 1.27-2.20), increased age at onset (OR, 1.0318; 95% CI, 1.03-1.04), premorbid mRS (OR, 1.1832; 95% CI, 1.13-1.24), brainstem lesions (OR, 1.6494; 95% CI, 1.39-1.96), and NIHSS (OR, 1.2073; 95% CI, 1.19-1.23). CONCLUSIONS: The incidence of dysphagia after ischemic stroke was 32.3%. The prediction model for the presence of dysphagia identified age, low BMI, premorbid disabilities, brainstem lesions, and NIHSS as predictive factors.


Assuntos
Transtornos de Deglutição/etiologia , AVC Isquêmico/complicações , Idoso , Estudos de Coortes , Avaliação da Deficiência , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recuperação de Função Fisiológica , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários
13.
J Pers Med ; 11(6)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208352

RESUMO

The objective of this study was to evaluate whether Cerebrolysin combined with rehabilitation therapy supports additional motor recovery in stroke patients with severe motor impairment. This study analyzed the combined data from the two phase IV prospective, multicenter, randomized, double-blind, placebo-controlled trials. Stroke patients were included within seven days after stroke onset and were randomized to receive a 21-day treatment course of either Cerebrolysin or placebo with standardized rehabilitation therapy. Assessments were performed at baseline, immediately after the treatment course, and 90 days after stroke onset. The plasticity of the motor system was assessed by diffusion tensor imaging and resting state fMRI. In total, 110 stroke patients were included for the full analysis set (Cerebrolysin n = 59, placebo n = 51). Both groups showed significant motor recovery over time. Repeated-measures analysis of varianceshowed a significant interaction between time and type of intervention as measured by the Fugl-Meyer Assessment (p < 0.05). The Cerebrolysin group demonstrated less degenerative changes in the major motor-related white matter tracts over time than the placebo group. In conclusion, Cerebrolysin treatment as an add-on to a rehabilitation program is a promising pharmacologic approach that is worth considering in order to enhance motor recovery in ischemic stroke patients with severe motor impairment.

14.
Stroke ; 52(10): 3167-3175, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34134508

RESUMO

Background and Purpose: The aim of this study was to verify the validity of the proportional recovery model in view of the ceiling effect of the Fugl-Meyer Assessment. Methods: We reviewed the medical records of patients enrolled in the Korean Stroke Cohort for Functioning and Rehabilitation between August 2012 and May 2015. Recovery proportion was defined as the actual change in Fugl-Meyer Assessment score of the upper extremity between 7 days and 6 months poststroke, relative to the initial neurological impairment. We then used logistic regression to identify clinical factors attributable to a ceiling effect of the Fugl-Meyer Assessment score of the upper extremity and propensity score matching to verify the validity of the proportional recovery rule. Results: We screened 10 636 patients and analyzed 849 patients (mean age, 65.4±11.9 years; female, 320 [37.7%]) with first-ever ischemic stroke. We found, through logistic regression analysis, that a one-unit increase in the initial neurological impairment and the age at stroke onset affected the odds ratio (1.0386 and 0.9736, respectively) of achieving the full Fugl-Meyer Assessment score of the upper limb at 6 months poststroke. We also demonstrated, through propensity score matching, that the difference in initial neurological impairment of the upper extremity resulted in discrepancy of the recovery proportion (0.92±0.20 [0­1] versus 0.81±0.31 [0­1], P<0.001). Conclusions: We demonstrated that the ceiling effect of the Fugl-Meyer Assessment score of the upper extremity is pronounced in patients with mild initial motor deficits of the upper extremity and that the recovery proportion varies according to the initial motor deficit of the upper limb using logistic regression analysis and propensity score matching, respectively. These results suggest that the proportional recovery model is not valid.


Assuntos
Recuperação de Função Fisiológica , Reabilitação do Acidente Vascular Cerebral/estatística & dados numéricos , Acidente Vascular Cerebral/fisiopatologia , Extremidade Superior/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Avaliação da Deficiência , Potenciais Evocados , Feminino , Humanos , AVC Isquêmico/fisiopatologia , AVC Isquêmico/reabilitação , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Pontuação de Propensão , República da Coreia , Resultado do Tratamento , Adulto Jovem
15.
Curr Oncol ; 28(3): 1927-1937, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065612

RESUMO

To identify cancer/testis (CT) antigens and immunogenic proteins, immunoscreening of testicular and small-cell lung cancer cell line NCI-H889 cDNA libraries was performed using serum obtained from a small-cell lung cancer (SCLC) patient. We obtained 113 positive cDNA clones comprised of 74 different genes, designated KP-SCLC-1 through KP-SCLC-74. Of these genes, 59 genes were found to be related to cancers by EMBASE analysis. Three of these antigens, including KP-SCLC-29 (NOL4), KP-SCLC-59 (CCDC83), and KP-SCLC-69 (KIF20B), were CT antigens. RT-PCR and western blot analysis showed that NOL4 was frequently present in small-cell lung cancer cell lines (8/9, 8/9). In addition, NOL4 mRNA was weakly, or at a low frequency, or not detected in various cancer cell lines. Our results reveal that NOL4 was expressed at protein levels in small-cell lung cancer tissues (10/10) but not detected in lung adenocarcinoma and squamous cell carcinoma by immunohistochemical analysis. Serological response to NOL4 was also evaluated by western blot assay using NOL4 recombinant protein. A humoral response against NOL4 proteins was detected in 75% (33/44) of small-cell lung cancer patients and in 65% (13/20) of healthy donors by a serological western blot assay. These data suggest that NOL4 is a specific target that may be useful for diagnosis and immunotherapy in SCLC.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Antígenos de Neoplasias/genética , Biblioteca Gênica , Humanos , Neoplasias Pulmonares/genética , Masculino , Proteínas Nucleares , Carcinoma de Pequenas Células do Pulmão/genética , Testículo
16.
Retina ; 41(11): 2301-2309, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33830961

RESUMO

PURPOSE: It is hypothesized that an unstable tear film would affect the quality and repeatability of optical coherence tomography angiography (OCTA). Therefore, OCTA repeatability according to tear break-up time (TBUT) was compared. METHODS: The 3 × 3 OCTA was performed twice and, the eyes were divided into 3 groups according to the TBUT (Group 1: TBUT ≤ 5 seconds, 43 eyes; Group 2: 5 seconds < TBUT ≤ 10 seconds, 35 eyes; Group 3: TBUT > 10 seconds, 34 eyes). The intraclass correlation coefficient, coefficient of variation, and test-retest SD were calculated and compared. RESULTS: The signal strengths of OCTA were 9.1 ± 1.2, 9.5 ± 0.8, and 9.5 ± 0.8 in each group from Groups 1, 2, and 3, respectively, which showed significant difference (P = 0.049). The intraclass correlation coefficient of vessel density were 0.733, 0.840, and 0.974 in Groups 1 to 3, respectively, and the values increased in the order of Groups 1, 2, and 3. The coefficient of variation were 6.41 ± 6.09, 3.29 ± 2.22, and 1.30 ± 1.17, and the test-retest SD were 0.83 ± 0.70, 0.47 ± 0.31, and 0.19 ± 0.17 in Groups 1, 2, and 3, respectively. The coefficient of variation and test-retest SD values decreased in the order of Groups 1, 2, and 3, and showed a significant difference (all, P < 0.05). CONCLUSION: The repeatability of OCTA tended to decrease with a shorter TBUT. When the TBUT is <5 seconds, care must be taken to interpret the OCTA results correctly.


Assuntos
Síndromes do Olho Seco/diagnóstico , Angiofluoresceinografia/métodos , Microvasos/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem , Lágrimas/metabolismo , Tomografia de Coerência Óptica/métodos , Adulto , Síndromes do Olho Seco/metabolismo , Feminino , Seguimentos , Fundo de Olho , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
17.
Front Neurosci ; 15: 629323, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841079

RESUMO

BACKGROUND: Brain disorders are gradually becoming the leading cause of death worldwide. However, the lack of knowledge of brain disease's underlying mechanisms and ineffective neuropharmacological therapy have led to further exploration of optimal treatments and brain monitoring techniques. OBJECTIVE: This study aims to review the current state of brain disorders, which utilize transcranial electrical stimulation (tES) and daily usable noninvasive neuroimaging techniques. Furthermore, the second goal of this study is to highlight available gaps and provide a comprehensive guideline for further investigation. METHOD: A systematic search was conducted of the PubMed and Web of Science databases from January 2000 to October 2020 using relevant keywords. Electroencephalography (EEG) and functional near-infrared spectroscopy were selected as noninvasive neuroimaging modalities. Nine brain disorders were investigated in this study, including Alzheimer's disease, depression, autism spectrum disorder, attention-deficit hyperactivity disorder, epilepsy, Parkinson's disease, stroke, schizophrenia, and traumatic brain injury. RESULTS: Sixty-seven studies (1,385 participants) were included for quantitative analysis. Most of the articles (82.6%) employed transcranial direct current stimulation as an intervention method with modulation parameters of 1 mA intensity (47.2%) for 16-20 min (69.0%) duration of stimulation in a single session (36.8%). The frontal cortex (46.4%) and the cerebral cortex (47.8%) were used as a neuroimaging modality, with the power spectrum (45.7%) commonly extracted as a quantitative EEG feature. CONCLUSION: An appropriate stimulation protocol applying tES as a therapy could be an effective treatment for cognitive and neurological brain disorders. However, the optimal tES criteria have not been defined; they vary across persons and disease types. Therefore, future work needs to investigate a closed-loop tES with monitoring by neuroimaging techniques to achieve personalized therapy for brain disorders.

18.
Acta Ophthalmol ; 99(7): e1056-e1062, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33555661

RESUMO

PURPOSE: To determine longitudinal changes of the ganglion cell-inner plexiform layer (GC-IPL) thickness in patients with non-exudative age-related macular degeneration (AMD) without other ophthalmic disease. METHODS: Thirty-three eyes of 33 patients with early and intermediate non-exudative AMD (non-exudative AMD group) and 33 normal control eyes were followed for 2 years, and GC-IPL thickness was measured by spectral domain optical coherence tomography at 1-year intervals. The mean rate of GC-IPL reduction was estimated using a linear mixed model and compared between two groups. RESULTS: The mean age of patients in the non-exudative AMD group and control groups were 68.82 ± 6.81 years and 67.73 ± 5.87 years, respectively (p = 0.488). The mean GC-IPL thickness at the first visit was 76.61 ± 16.33 µm in the non-exudative AMD and 81.76 ± 3.69 µm in control group (p = 0.387), and these values significantly decreased over time, with an average reduction rate of average GC-IPL -0.86 µm/year in the non-exudative AMD group and -0.32 µm/year in the control group. The difference between two groups was statistically significant (p < 0.001), and there was also a significant interaction between group and duration in linear mixed models in mean GC-IPL thickness (p = 0.001). CONCLUSIONS: The reduction rate of the GC-IPL thickness was greater in non-exudative AMD eyes, even at relatively early stages of the disease. Physicians should maintain awareness of the presence of non-exudative AMD in various cases of ophthalmic diseases where GC-IPL thickness evaluation is necessary.


Assuntos
Degeneração Macular/diagnóstico , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Idoso , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Fibras Nervosas/patologia , Estudos Prospectivos
19.
Eye (Lond) ; 35(11): 3064-3070, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33423044

RESUMO

PURPOSE: To compare visual improvements between initial intravitreal t-PA with gas injection before anti-vascular endothelial growth factor (VEGF) and anti-VEGF injection monotherapy for submacular haemorrhage (SMH) associated with age-related macular degeneration (AMD). METHODS: We retrospectively reviewed medical records of naive patients treated with intravitreal t-PA with gas injection before anti-VEGF (Group 1) or only with intravitreal anti-VEGF injection (Group 2) for SMH [disc area (DA) ≥ 2] associated with AMD from two institutions. Both groups received 3 monthly loads of anti-VEGF injections followed by injections as needed for AMD treatment. Changes in best-corrected visual acuity (BCVA, logMAR) between the initial visit and after 6 months of treatment were compared between two groups. RESULTS: A total of 82 patients were enroled. Of these, 32 patients and 50 patients were grouped in Groups 1 and 2, respectively. The mean change in BCVA over 6 months for Group 1 was -0.52 ± 0.88, which was significantly larger (p = 0.044) than the mean change for Group 2 (-0.15 ± 0.58). We compared visual improvements between the two groups based on the following SMH size categories: ≤5, >5, and ≤15, and >15 DA. When the SMH size was ≤5, or >5 and ≤15 DA, the mean change in BCVA was larger for Group 1 than for Group 2, but this difference was not significant. When SMH size was >15 DA, Group 1 patients exhibited a mean visual improvement of -0.79 ± 0.80, which was significantly greater (p = 0.029) than that of Group 2 (-0.06 ± 0.67). CONCLUSIONS: Patients that were primarily treated for SMH associated with AMD using t-PA and gas injection (followed by anti-VEGF injection) exhibited better visual improvement than those treated with anti-VEGF monotherapy, especially in patients exhibiting larger SMH sizes (>15 DA) at the initial visit.


Assuntos
Degeneração Macular , Ativador de Plasminogênio Tecidual , Fibrinolíticos/uso terapêutico , Angiofluoresceinografia , Humanos , Degeneração Macular/complicações , Degeneração Macular/tratamento farmacológico , Hemorragia Retiniana/tratamento farmacológico , Hemorragia Retiniana/etiologia , Estudos Retrospectivos , Acuidade Visual
20.
Lung ; 199(1): 55-61, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33458798

RESUMO

INTRODUCTION: The purpose of this study was to identify the prevalence and severity of dysphagia in patients diagnosed with aspiration pneumonia, with and without neurologic disorders. METHODS: We retrospectively reviewed the medical records of inpatients with aspiration pneumonia who underwent a videofluoroscopic swallowing study (VFSS) for evaluation of dysphagia. Patients were divided into two groups based on the presence or absence of neurologic disorders. The prevalence and severity of aspiration and pharyngeal residue due to dysphagia were assessed using the penetration-aspiration scale (PAS) and pharyngeal residue grade (PRG). RESULTS: A total of 784 patients were enrolled; of these, 58.7% were males and the mean age was 76.12 ± 6.69. Penetration-aspiration-related dysphagia (PAS scores 3-8) was seen in 56.5% of all subjects, and 32.5% showed silent aspiration (PAS 8). Pharyngeal residue-related dysphagia (PRG scores 2-3) was seen in 65.2% of all patients, and the PAS and PRG were positively correlated. On dividing the subjects into two groups based on the presence of neurologic disorders, there was no significant difference in prevalence of the dysphagia between groups (PAS: p = 0.641; PRG: p = 0.872) with the proportion of silent aspiration (p = 0.720). CONCLUSION: In patients hospitalized for aspiration pneumonia, there was a high prevalence of dysphagia. There were no differences in the prevalence and severity of dysphagia in patients with aspiration pneumonia based on the presence or absence of a neurologic disorder. Therefore, diagnostic evaluation of dysphagia is necessary regardless of the presence of neurologic disorders.


Assuntos
Transtornos de Deglutição/etiologia , Fluoroscopia , Pneumonia Aspirativa/complicações , Gravação em Vídeo , Idoso , Transtornos de Deglutição/diagnóstico , Feminino , Humanos , Masculino , Prevalência , Estudos Retrospectivos , Índice de Gravidade de Doença
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