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1.
J Cell Mol Med ; 28(12): e18489, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38899522

RESUMEN

This study explores the impact of senescence on autocrine C-C motif chemokine ligand 5 (CCL5) in human endothelial progenitor cell (EPCs), addressing the poorly understood decline in number and function of EPCs during ageing. We examined the effects of replication-induced senescence on CCL5/CCL5 receptor (CCR5) signalling and angiogenic activity of EPCs in vitro and in vivo. We also explored microRNAs controlling CCL5 secretion in senescent EPCs, its impact on EPC angiogenic activity, and validated our findings in humans. CCL5 secretion and CCR5 levels in senescent EPCs were reduced, leading to attenuated angiogenic activity. CCL5 enhanced EPC proliferation via the CCR5/AKT/P70S6K axis and increased vascular endothelial growth factor (VEGF) secretion. Up-regulation of miR-409 in senescent EPCs resulted in decreased CCL5 secretion, inhibiting the angiogenic activity, though these negative effects were counteracted by the addition of CCL5 and VEGF. In a mouse hind limb ischemia model, CCL5 improved the angiogenic activity of senescent EPCs. Analysis involving 62 healthy donors revealed a negative association between CCL5 levels, age and Framingham Risk Score. These findings propose CCL5 as a potential biomarker for detection of EPC senescence and cardiovascular risk assessment, suggesting its therapeutic potential for age-related cardiovascular disorders.


Asunto(s)
Senescencia Celular , Quimiocina CCL5 , Células Progenitoras Endoteliales , MicroARNs , Neovascularización Fisiológica , Animales , Humanos , Masculino , Ratones , Angiogénesis , Proliferación Celular , Quimiocina CCL5/metabolismo , Quimiocina CCL5/genética , Regulación hacia Abajo/genética , Células Progenitoras Endoteliales/metabolismo , Células Progenitoras Endoteliales/citología , Isquemia/metabolismo , Isquemia/patología , Isquemia/genética , MicroARNs/genética , MicroARNs/metabolismo , Neovascularización Fisiológica/genética , Receptores CCR5/metabolismo , Receptores CCR5/genética , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética
2.
Arterioscler Thromb Vasc Biol ; 43(10): 1935-1951, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37589139

RESUMEN

BACKGROUND: We examined the role of Panxs (pannexins) in human endothelial progenitor cell (EPC) senescence. METHODS: Young and replication-induced senescent endothelial colony-forming cells (ECFCs) derived from human circulating EPCs were used to examine cellular activities and senescence-associated indicators after transfection of short interference RNA specific to Panx1 or lentivirus-mediated Panx1 overexpression. Hind limb ischemia mice were used as in vivo angiogenesis model. Protein and phospho-kinase arrays were used to determine underlying mechanisms. RESULTS: Panx1 was the predominant Panx isoform in human ECFCs and upregulated in both replication-induced senescent ECFCs and circulating EPCs from aged mice and humans. Cellular activities of the young ECFCs were enhanced by Panx1 downregulation but attenuated by its upregulation. In addition, reduction of Panx1 in the senescent ECFCs could rejuvenate cellular activities with reduced senescence-associated indicators, including senescence-associated ß-galactosidase activity, p16INK4a (cyclin-dependent kinase inhibitor 2A), p21 (cyclin-dependent kinase inhibitor 1), acetyl-p53 (tumor protein P53), and phospho-histone H2A.X (histone family member X). In mouse ischemic hind limbs injected senescent ECFCs, blood perfusion ratio, salvaged limb outcome, and capillary density were all improved by Panx1 knockdown. IGF-1 (insulin-like growth factor 1) was significantly increased in the supernatant from senescent ECFCs after Panx1 knockdown. The enhanced activities and paracrine effects of Panx1 knockdown senescent ECFCs were completely inhibited by anti-IGF-1 antibodies. FAK (focal adhesion kinase), ERK (extracellular signal-regulated kinase), and STAT3 (signal transducer and activator of transcription 3) were activated in senescent ECFCs with Panx1 knockdown, in which the intracellular calcium level was reduced, and the activation was inhibited by supplemented calcium. The increased IGF-1 in Panx1-knockdown ECFCs was abrogated, respectively, by inhibitors of FAK (PF562271), ERK (U0126), and STAT3 (NSC74859) and supplemented calcium. CONCLUSIONS: Panx1 expression is upregulated in human ECFCs/EPCs with replication-induced senescence and during aging. Angiogenic potential of senescent ECFCs is improved by Panx1 reduction through increased IGF-1 production via activation of the FAK-ERK axis following calcium influx reduction. Our findings provide new strategies to evaluate EPC activities and rejuvenate senescent EPCs for therapeutic angiogenesis.


Asunto(s)
Factor I del Crecimiento Similar a la Insulina , Proteína p53 Supresora de Tumor , Animales , Humanos , Ratones , Calcio/metabolismo , Células Cultivadas , Senescencia Celular , Conexinas/genética , Conexinas/metabolismo , Quinasas Ciclina-Dependientes/metabolismo , Quinasas Ciclina-Dependientes/farmacología , Isquemia/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Proteína p53 Supresora de Tumor/genética
3.
Network ; : 1-29, 2024 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-38433470

RESUMEN

As the number of patients increases, physicians are dealing with more and more cases of degenerative spine pathologies on a daily basis. To reduce the workload of healthcare professionals, we propose a modified Swin-UNet network model. Firstly, the Swin Transformer Blocks are improved using a residual post-normalization and scaling cosine attention mechanism, which makes the training process of the model more stable and improves the accuracy. Secondly, we use the log-space continuous position biasing method instead of the bicubic interpolation position biasing method. This method solves the problem of performance loss caused by the large difference between the resolution of the pretraining image and the resolution of the spine image. Finally, we introduce a segmentation smooth module (SSM) at the decoder stage. The SSM effectively reduces redundancy, and enhances the segmentation edge processing to improve the model's segmentation accuracy. To validate the proposed method, we conducted experiments on a real dataset provided by hospitals. The average segmentation accuracy is no less than 95%. The experimental results demonstrate the superiority of the proposed method over the original model and other models of the same type in segmenting the spinous processes of the vertebrae and the posterior arch of the spine.

4.
Pediatr Int ; 66(1): e15777, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38863264

RESUMEN

BACKGROUND: We aimed to compare the clinical features and severity of the Omicron and Delta variant infections among children hospitalized for coronavirus disease 2019 (COVID-19). METHODS: Children 12 years old or less hospitalized for COVID-19 across five hospitals between January 1, 2021 and March 31, 2022 were identified using the state's pediatric COVID-19 registry. Delta and Omicron-infected patients without previous COVID-19 infection, COVID-19 vaccination, or co-infections were propensity-score matched 1:1 to control for differences in baseline characteristics. Clinical manifestations, treatments, and outcomes were analyzed. Disease severity was assessed using an adapted WHO ordinal scale. RESULTS: Of the initial 1367 patients, 668 had Delta infection and 699 had Omicron infection. Propensity-score matching produced 558 matched pairs. Patients with Omicron infection were more likely to present with croup (the odds ratio, OR, was 10.87, with a 95% confidence interval, CI, ranging from 2.54 to 46.59), lower respiratory tract infection (OR 2.32, 95% CI, 1.48-3.64) and seizures (OR 8.39, 95% CI, 5.04-13.99) compared with those with Delta infection. Omicron was associated with increased odds of moderate/severe disease (OR 6.14, 95% CI, 4.72-7.99) and a greater need for intravenous fluid therapy (OR 6.00, 95% CI, 4.29-8.39), corticosteroids (OR 3.08, 95% CI, 1.66-5.72), empirical antibiotics (OR 1.70, 95% CI, 1.10-2.64), and low-flow nasal oxygen therapy (OR 3.68, 95% CI, 2.17-6.22) in comparison with Delta. CONCLUSION: Children hospitalized with Omicron infection demonstrated a distinct clinical profile compared to those with Delta infection, with increased likelihood of moderate/severe disease and higher utilization of health-care resources.


Asunto(s)
COVID-19 , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Humanos , COVID-19/epidemiología , Niño , Masculino , Femenino , Preescolar , Lactante , Hospitalización/estadística & datos numéricos , Puntaje de Propensión , Estudios Retrospectivos , Sistema de Registros
5.
Int J Mol Sci ; 25(13)2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-39000454

RESUMEN

Chronic obstructive pulmonary disease (COPD) plays a significant role in global morbidity and mortality rates, typified by progressive airflow restriction and lingering respiratory symptoms. Recent explorations in molecular biology have illuminated the complex mechanisms underpinning COPD pathogenesis, providing critical insights into disease progression, exacerbations, and potential therapeutic interventions. This review delivers a thorough examination of the latest progress in molecular research related to COPD, involving fundamental molecular pathways, biomarkers, therapeutic targets, and cutting-edge technologies. Key areas of focus include the roles of inflammation, oxidative stress, and protease-antiprotease imbalances, alongside genetic and epigenetic factors contributing to COPD susceptibility and heterogeneity. Additionally, advancements in omics technologies-such as genomics, transcriptomics, proteomics, and metabolomics-offer new avenues for comprehensive molecular profiling, aiding in the discovery of novel biomarkers and therapeutic targets. Comprehending the molecular foundation of COPD carries substantial potential for the creation of tailored treatment strategies and the enhancement of patient outcomes. By integrating molecular insights into clinical practice, there is a promising pathway towards personalized medicine approaches that can improve the diagnosis, treatment, and overall management of COPD, ultimately reducing its global burden.


Asunto(s)
Biomarcadores , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/genética , Humanos , Biomarcadores/metabolismo , Estrés Oxidativo , Proteómica/métodos , Genómica/métodos , Metabolómica/métodos , Epigénesis Genética
6.
Medicina (Kaunas) ; 60(2)2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38399533

RESUMEN

Background and Objectives: Recent studies suggest that hydrogen gas possesses anti-inflammatory, antioxidant, and anti-apoptotic properties. This study aimed to explore the therapeutic potential of hydrogen gas and assess its safety and tolerability in individuals with chronic obstructive pulmonary disease (COPD). Materials and Methods: Enrolled COPD patients received standard treatments along with additional hydrogen inhalation for 30 min in the morning, afternoon, and evening over a 30-day period. The assessment included changes in the COPD Assessment Test (CAT), the modified Medical Research Council (mMRC) Dyspnea Scale, lung function, sleep quality, inflammation markers, and oxidative stress markers before and after hydrogen inhalation. Results: Six patients participated in this study. Patients 2, 3, 4, 5, and 6 demonstrated improvements in CAT scores following hydrogen gas intervention, with patients 2, 4, 5, and 6 also showing improvements in mMRC scores. Statistically, this study revealed significant improvements in CAT [15.5 (10.5-19.75) vs. 8.5 (3-13.5); p = 0.043] and mMRC scores [2.5 (1-4) vs. 2 (0-3.25); p = 0.046] before and after intervention, respectively. However, no significant differences were observed in lung function, DLCO, sleep quality, and 6 MWT before and after hydrogen therapy. CBC examination showed a significant difference in platelet count before and after treatment [247 (209.75-298.75) vs. 260 (232.75-314.5); p = 0.043], respectively, while other blood tests, inflammation markers, and oxidative stress markers did not exhibit significant differences before and after hydrogen therapy. All patients experienced no obvious side-effects. Conclusions: Adjuvant therapy with hydrogen gas demonstrated symptom improvements in specific COPD patients, and no significant adverse effects were observed in any of the patients. Hydrogen gas may also exert a modulatory effect on platelet count.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Humanos , Volumen Espiratorio Forzado , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Atención Odontológica , Inflamación , Terapia Combinada , Índice de Severidad de la Enfermedad
7.
BMC Infect Dis ; 23(1): 398, 2023 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-37308825

RESUMEN

BACKGROUND: Children account for a significant proportion of COVID-19 hospitalizations, but data on the predictors of disease severity in children are limited. We aimed to identify risk factors associated with moderate/severe COVID-19 and develop a nomogram for predicting children with moderate/severe COVID-19. METHODS: We identified children ≤ 12 years old hospitalized for COVID-19 across five hospitals in Negeri Sembilan, Malaysia, from 1 January 2021 to 31 December 2021 from the state's pediatric COVID-19 case registration system. The primary outcome was the development of moderate/severe COVID-19 during hospitalization. Multivariate logistic regression was performed to identify independent risk factors for moderate/severe COVID-19. A nomogram was constructed to predict moderate/severe disease. The model performance was evaluated using the area under the curve (AUC), sensitivity, specificity, and accuracy. RESULTS: A total of 1,717 patients were included. After excluding the asymptomatic cases, 1,234 patients (1,023 mild cases and 211 moderate/severe cases) were used to develop the prediction model. Nine independent risk factors were identified, including the presence of at least one comorbidity, shortness of breath, vomiting, diarrhea, rash, seizures, temperature on arrival, chest recessions, and abnormal breath sounds. The nomogram's sensitivity, specificity, accuracy, and AUC for predicting moderate/severe COVID-19 were 58·1%, 80·5%, 76·8%, and 0·86 (95% CI, 0·79 - 0·92) respectively. CONCLUSION: Our nomogram, which incorporated readily available clinical parameters, would be useful to facilitate individualized clinical decisions.


Asunto(s)
COVID-19 , Modelos Estadísticos , Humanos , Niño , Pronóstico , Factores de Riesgo , Gravedad del Paciente
8.
J Oncol Pharm Pract ; 29(6): 1374-1380, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36112905

RESUMEN

BACKGROUND: Painful paronychia and pseudopyogenic granuloma (PG) are common adverse drug reactions (ADRs) associated with the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) to treat non-small cell lung cancer (NSCLC). Multiple local management approaches have been tested with unsatisfactory results. We have introduced an occlusion therapy technique through which available topical drugs for longer than 2 years. METHODS: Based on the cancer registry and case management system of our hospital, from July 2019 to July 2020, we retrospectively enrolled patients with NSCLC who were treated with EGFR-TKIs and received applications of 0.5% timolol ophthalmic solution (TIMOPTOL XE 0.5%®) combined with a neomycin/tyrothricin ointment (Biomycin®) using the occlusion method to treat paronychia or PG. RESULTS: A total of 22 patients were enrolled, with a mean age of 66.5 years, most of whom were women (72.7%). Periungual lesion-related pain was reported by all patients, and periungual bleeding and PG were reported in 14% (3/22) and 64% (14/22) of patients, respectively. After the occlusion therapy application of timolol ophthalmic solution combined with neomycin/tyrothricin ointment twice daily, the overall response rate was 83.3%, including complete response in 18% (4/22) of cases and partial response in 68% (15/22) of cases. CONCLUSION: We presented an occlusion method using available topical beta-blockers and antibiotic ointment for EGFR-TKI-induced paronychia and PG in Taiwan. The result is favorable. Further randomized control trial is urgent to validate our findings.


Asunto(s)
Hiperplasia Angiolinfoide con Eosinofilia , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Paroniquia , Humanos , Femenino , Anciano , Masculino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Timolol/efectos adversos , Hiperplasia Angiolinfoide con Eosinofilia/inducido químicamente , Hiperplasia Angiolinfoide con Eosinofilia/tratamiento farmacológico , Estudios Retrospectivos , Antibacterianos/efectos adversos , Paroniquia/inducido químicamente , Paroniquia/tratamiento farmacológico , Pomadas/efectos adversos , Taiwán , Inhibidores de Proteínas Quinasas/efectos adversos , Neomicina/efectos adversos , Receptores ErbB , Tirotricina/efectos adversos , Soluciones Oftálmicas/efectos adversos , Mutación
9.
Pediatr Int ; 65(1): e15565, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37368506

RESUMEN

BACKGROUND: This study aimed to describe the clinical characteristics and severity of young infants hospitalized with COVID-19 and study the relationship between breastfeeding and maternal COVID-19 vaccination on the severity of COVID-19. METHODS: A retrospective, observational study was performed among infants aged 6 months and below hospitalized for COVID-19 in a tertiary state hospital in Malaysia between February 1 and April 30, 2022. The primary outcome was "serious disease," defined as pneumonia requiring respiratory support or dehydration with warning signs. Multivariate logistic regression was used to determine independent predictors for serious disease. RESULTS: A total of 102 infants were included in the study; 53.9% were males with a median age of 11 weeks (interquartile range: 5-20 weeks). Sixteen patients (15.7%) had pre-existing comorbidities, including preterm birth. Fever was the most common presenting symptom (82.4%), followed by cough (53.9%), and rhinorrhea (31.4%). Forty-one infants (40.2%) presented with serious disease, warranting either respiratory support or intravenous fluid therapy for dehydration. Recent maternal COVID-19 vaccination was associated with a reduced risk of serious disease on univariate analysis but was not significant after multivariate adjustment (adjusted odds ratio [aOR] 0.39; 95% CI: 0.14-1.11; p = 0.08). Exclusive breastfeeding was protective against serious COVID-19 in young infants, independent of other confounding factors (aOR 0.21, 95% CI: 0.06-0.71; p = 0.01). CONCLUSION: COVID-19 is a serious disease with non-specific clinical manifestations in young infants. Exclusive breastfeeding could play an important protective role.


Asunto(s)
Lactancia Materna , COVID-19 , Deshidratación , Neumonía , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Lactancia Materna/efectos adversos , COVID-19/diagnóstico , COVID-19/epidemiología , Vacunas contra la COVID-19/administración & dosificación , Deshidratación/complicaciones , Deshidratación/epidemiología , Gravedad del Paciente , Estudios Retrospectivos , Factores de Riesgo , Neumonía/complicaciones , Neumonía/epidemiología , Respiración Artificial , Hospitalización
10.
Pediatr Int ; 65(1): e15690, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38037505

RESUMEN

BACKGROUND: We describe the epidemiology, clinical characteristics, and outcomes of multisystem inflammatory syndrome in children (MIS-C) among children from Negeri Sembilan, Malaysia. METHODS: A retrospective, multicentre, observational study was performed among children ≤15 years old who were hospitalized for MIS-C between January 18, 2021 and June 30, 2023. The incidence of MIS-C was estimated using reported SARS-CoV-2 cases and census population data. Descriptive analyses were used to summarize the clinical presentation and outcomes. RESULTS: The study included 53 patients with a median age of 5.7 years (IQR 1.8-8.7 years); 75.5% were males. The overall incidence of MIS-C was approximately 5.9 cases per 1,000,000 person-months. Pediatric intensive care unit (PICU) admission was required for 22 (41.5%) patients. No mortalities were recorded. Children aged 6-12 years were more likely to present with cardiac dysfunction/shock (odds ratio [OR] 5.43, 95% confidence interval [CI] 1.67-17.66), whereas children below 6 years were more likely to present with a Kawasaki disease phenotype (OR 5.50, 95% CI 1.33-22.75). Twenty patients (37.7%) presented with involvement of at least four organ systems, but four patients (7.5%) demonstrated single-organ system involvement. CONCLUSION: An age-based variation in the clinical presentation of MIS-C was demonstrated. Our findings suggest MIS-C could manifest in a spectrum, including single-organ involvement. Despite the high requirement for PICU admission, the prognosis of MIS-C was favorable, with no recorded mortalities.


Asunto(s)
COVID-19 , Síndrome de Respuesta Inflamatoria Sistémica , Niño , Masculino , Humanos , Lactante , Preescolar , Adolescente , Femenino , Estudios Retrospectivos , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Síndrome de Respuesta Inflamatoria Sistémica/terapia , COVID-19/epidemiología , COVID-19/terapia , SARS-CoV-2
11.
Sensors (Basel) ; 23(13)2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37447987

RESUMEN

Distributed Denial of Service (DDoS) attacks pose a significant threat to internet and cloud security. Our study utilizes a Poisson distribution model to efficiently detect DDoS attacks with a computational complexity of O(n). Unlike Machine Learning (ML)-based algorithms, our method only needs to set up one or more Poisson models for legitimate traffic based on the granularity of the time periods during preprocessing, thus eliminating the need for training time. We validate this approach with four virtual machines on the CDX 3.0 platform, each simulating different aspects of DDoS attacks for offensive, monitoring, and defense evaluation purposes. The study further analyzes seven diverse DDoS attack methods. When compared with existing methods, our approach demonstrates superior performance, highlighting its potential effectiveness in real-world DDoS attack detection.


Asunto(s)
Algoritmos , Internet , Aprendizaje Automático
12.
Sensors (Basel) ; 23(23)2023 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-38067952

RESUMEN

Due to frequent traffic accidents around the world, people often take out car insurance to mitigate their losses and receive compensation in a traffic accident. However, in the existing car insurance claims process, there are problems such as insurance fraud, inability to effectively track and transmit insurance data, cumbersome insurance procedures, and high insurance data storage costs. Since the immutability and traceability features of blockchain technology can prevent data manipulation and trace past data, we have used the Elliptic Curve Digital Signature Algorithm (ECDSA) to sign and encrypt car insurance data, ensuring both data integrity and security. We propose a blockchain and IPFS-based anticounterfeiting and traceable car insurance claims system to improve the above problems. We incorporate the Interplanetary File System (IPFS) to reduce the cost of storing insurance data. This study also attempts to propose an arbitration mechanism in the event of a car insurance dispute.

13.
Medicina (Kaunas) ; 59(2)2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36837592

RESUMEN

Background and Objectives: Exertional desaturation (ED) is common and is associated with poorer clinical outcomes in chronic obstructive pulmonary disease (COPD). The age, dyspnea, airflow obstruction (ADO) and body mass index, airflow obstruction, dyspnea, and exercise (BODE) indexes are used to predict the prognosis of COPD patients. This study aimed to investigate the relationship between these indexes, pulmonary function, medical costs, and ED in COPD patients. Materials and Methods: Data were collected from the electronic database of the Kaohsiung Chang Gung Memorial Hospital. This retrospective study included 396 patients categorized as either ED (n = 231) or non-ED (n = 165). Variables (including age, smoking history, body mass index (BMI), pulmonary function test, maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP), six minutes walking test distance (6MWD), SpO2, COPD Assessment Test (CAT) score, ADO index, BODE index, Charlson comorbidity index (CCI), and medical costs) were compared between the two groups, and their correlations were assessed. ED was defined as SpO2 less than 90% or SpO2 decrease of more than 4% compared to baseline levels during 6MWT. Results: A significant statistical difference was found regarding a lower score of the ADO index and the BODE index (both p < 0.001), better pulmonary function (forced expiratory volume in the first second (FEV1), p < 0.001; FEV1/ forced vital capacity (FVC), p < 0.001; diffusion capacity of the lung for carbon monoxide (DLCO), p < 0.001), and higher minimal oxygen saturation (p < 0.001) in non-ED COPD patients. No difference was found in the distance of the 6MWT (p = 0.825) and respiratory muscle strength (MIP; MEP, p = 0.86; 0.751). However, the adjusted multivariate logistic regression analysis showed that only SpO2 (minimal) had a significant difference between of the ED and non-ED group (p < 0.001). There was either no difference in the medical expenses between ED and non-ED COPD patients. Conclusions: SpO2 (minimal) during the 6MWT is the independent factor for ED. ED is related to BODE and ADO indices, but is not related to medical expense.


Asunto(s)
Tolerancia al Ejercicio , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Disnea , Pulmón , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Costos de la Atención en Salud , Pruebas de Función Respiratoria
14.
Medicina (Kaunas) ; 59(3)2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36984578

RESUMEN

Background and Objectives:The ADO (age, dyspnea, and airflow obstruction) and BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) indices are often used to evaluate the prognoses for chronic obstructive pulmonary disease(COPD); however, an index suitable for predicting medical costs has yet to be developed. Materials and Methods: We investigated the BODE and ADO indices to predict medical costs and compare their predictive power. A total of 396 patients with COPD were retrospectively enrolled. Results: For hospitalization frequencies, BODE was R2 = 0.093 (p < 0.001), and ADO was R2 = 0.065 (p < 0.001); for hospitalization days, BODE was R2 = 0.128 (p < 0.001), and ADO was R2 = 0.071 (p < 0.001); for hospitalization expenses, BODE was R2 = 0.020 (p = 0.047), and ADO was R2 = 0.012 (p = 0.179). BODE and ADO did not differ significantly in the numbers of outpatient visits (BODE, R2 = 0.012, p = 0.179; ADO, R2 = 0.017, p = 0.082); outpatient medical expenses (BODE, R2 = 0.012, p = 0.208; ADO, R2 = 0.008, p = 0.364); and total medical costs (BODE, R2 = 0.018, p = 0.072; ADO, R2 = 0.016, p = 0.098). In conclusion, BODE and ADO indices were correlated with hospitalization frequency and hospitalization days. However, the BODE index exhibits slightly better predictive accuracy than the ADO index in these items.


Asunto(s)
Costos de la Atención en Salud , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Índice de Masa Corporal , Estudios de Cohortes , Disnea/etiología , Pulmón , Enfermedad Pulmonar Obstructiva Crónica/economía , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
15.
J Org Chem ; 87(22): 15327-15332, 2022 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-36302512

RESUMEN

Hexamethyldisilazane was reacted with formamides to generate N,N-disubstituent formimidamide, after which a reaction with sulfonamides was induced to form sulfonylformamidines. This protocol can be applied for arylformamidine formation in which anilines are used as substrates under optimized conditions. The advantages of this method are high efficiency, structural diversity in products with good yields, and applicability in large-scale operations.


Asunto(s)
Formamidas , Compuestos de Organosilicio , Formamidas/química , Aminas/química , Sulfonamidas/química , Sulfanilamida
16.
Arterioscler Thromb Vasc Biol ; 41(2): 915-930, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33356390

RESUMEN

OBJECTIVE: Circulating progenitor cells possess vasculogenesis property and participate in repair of vascular injury. Cx (connexin) 43-a transmembrane protein constituting gap junctions-is involved in vascular pathology. However, the role of Cx43 in smooth muscle progenitor cells (SPCs) remained unclear. Approach and Results: Human SPCs cultured from CD34+ peripheral blood mononuclear cells expressed smooth muscle cell markers, such as smooth muscle MHC (myosin heavy chain), nonmuscle MHC, calponin, and CD140B, and Cx43 was the most abundant Cx isoform. To evaluate the role of Cx43 in SPCs, short interference RNA was used to knock down Cx43 expression. Cellular activities of SPCs were reduced by Cx43 downregulation. In addition, Cx43 downregulation attenuated angiogenic potential of SPCs in hind limb ischemia mice. Protein array and ELISA of the supernatant from SPCs showed that IL (interleukin)-6, IL-8, and HGF (hepatocyte growth factor) were reduced by Cx43 downregulation. Simultaneously, Cx43 downregulation reduced the phosphorylation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and Akt (protein kinase B) pathway and reactivation of NF-κB and Akt using betulinic acid, and SC79 could restore the secretion of growth factors and cytokines. Moreover, FAK (focal adhesion kinase)-Src (proto-oncogene tyrosine-protein kinase Src) activation was increased by Cx43 downregulation, and inactivation of Akt-NF-κB could be restored by Src inhibitor (PP2), indicating that Akt-NF-κB inactivated by Cx43 downregulation arose from FAK-Src activation. Finally, the depressed cellular activities and secretion of SPCs after Cx43 downregulation were restored by FAK inhibitor PF-562271 or PP2. CONCLUSIONS: SPCs possess angiogenic potential to repair ischemic tissue mainly through paracrine effects. Gap junction protein Cx43 plays an important role in regulating cellular function and paracrine effects of SPCs through FAK-Src axis.


Asunto(s)
Conexina 43/metabolismo , Isquemia/cirugía , Músculo Esquelético/irrigación sanguínea , Miocitos del Músculo Liso/trasplante , FN-kappa B/metabolismo , Neovascularización Fisiológica , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Movimiento Celular , Proliferación Celular , Células Cultivadas , Conexina 43/genética , Modelos Animales de Enfermedad , Regulación hacia Abajo , Femenino , Miembro Posterior , Humanos , Mediadores de Inflamación/metabolismo , Isquemia/genética , Isquemia/metabolismo , Isquemia/fisiopatología , Ratones Endogámicos BALB C , Ratones Desnudos , Ratones Transgénicos , Miocitos del Músculo Liso/metabolismo , Fosforilación , Proto-Oncogenes Mas , Interferencia de ARN , Flujo Sanguíneo Regional , Transducción de Señal , Trasplante de Células Madre
17.
BMC Anesthesiol ; 22(1): 260, 2022 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-35971080

RESUMEN

BACKGROUND: The mainstream facilitation of one-lung ventilation is using double-lumen endobronchial tubes. However, it is more difficult to be positioned properly and more likely to cause airway injuries. How to place double-lumen endobronchial tubes rapidly and correctly is important for thoracic anesthesiologists. METHODS: One hundred eight patients with an American Society of Anesthesiologists physical status of I to III were 20 years of age or over, and required one-lung ventilation for thoracic surgery. They were randomly assigned to the conventional technique group (n = 36), the flexible fiberoptic bronchoscopy group (n = 36), or the Trachway® flexible stylet group (n = 36). The primary endpoint was the time needed for intubation. T1, the time from the tip of the blade passing between the patient's lips to identification of the vocal cords; and T2, the time from identification of the vocal cords to the bronchial lumen was in the correct position. RESULTS: T1 had no significant difference between groups, but T2 was significantly shorter in the Trachway® flexible stylet group (p < 0.0001) and longer in the conventional technique group (p < 0.0001). CONCLUSIONS: Using Trachway® flexible stylet for correct placement of double-lumen endobronchial tubes not only significantly shortened the intubation time, but also reduced incidence of carinal injuries. It is an alternative, and a choice with good safety. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02364622, 18/02/2015, Retrospectively registered.


Asunto(s)
Intubación Intratraqueal , Ventilación Unipulmonar , Bronquios , Broncoscopía/métodos , Humanos , Intubación Intratraqueal/métodos , Estudios Prospectivos
18.
J Paediatr Child Health ; 58(5): 769-773, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34723402

RESUMEN

AIM: Households are a significant venue for the transmission of SARS-CoV-2. We conducted a study to characterise the transmission dynamics and identify risk factors for household transmission of SARS-CoV-2 in Negeri Sembilan, Malaysia. METHODS: This retrospective observational study included 185 families of paediatric COVID-19 cases from 1 February 2020 to 31 December 2020. We identified the index case for each household and gathered the socio-demographic, epidemiological investigation results and risk factors for household transmission from medical case records. The secondary attack rate was calculated, and logistic regression analyses were used to identify risk factors associated with secondary household transmission of SARS-CoV-2. RESULTS: Of the 848 household contacts, 466 acquired secondary infections, resulting in a secondary attack rate of 55%. The median age of the secondary cases was 12 years. Female household contacts and household contacts who slept in the same room with the index case were significantly associated with increased risk for COVID-19. Other independent risk factors associated with higher transmission risk in the household included an index case who was symptomatic, a household index case aged greater than 18 years and a male household index case. CONCLUSIONS: High rates of household transmission of COVID-19 were found, indicating households were a major setting of transmission of SARS-CoV-2. Our data provide insight into the risk factors for household transmission of SARS-CoV-2 in Malaysia.


Asunto(s)
COVID-19 , SARS-CoV-2 , Anciano , COVID-19/epidemiología , Niño , Composición Familiar , Femenino , Humanos , Malasia/epidemiología , Masculino , Factores de Riesgo
19.
Sensors (Basel) ; 22(14)2022 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-35890848

RESUMEN

Smart devices have become an essential part of the architectures such as the Internet of Things (IoT), Cyber-Physical Systems (CPSs), and Internet of Everything (IoE). In contrast, these architectures constitute a system to realize the concept of smart cities and, ultimately, a smart planet. The adoption of these smart devices expands to different cyber-physical systems in smart city architecture, i.e., smart houses, smart healthcare, smart transportation, smart grid, smart agriculture, etc. The edge of the network connects these smart devices (sensors, aggregators, and actuators) that can operate in the physical environment and collects the data, which is further used to make an informed decision through actuation. Here, the security of these devices is immensely important, specifically from an authentication standpoint, as in the case of unauthenticated/malicious assets, the whole infrastructure would be at stake. We provide an updated review of authentication mechanisms by categorizing centralized and distributed architectures. We discuss the security issues regarding the authentication of these IoT-enabled smart devices. We evaluate and analyze the study of the proposed literature schemes that pose authentication challenges in terms of computational costs, communication overheads, and models applied to attain robustness. Hence, lightweight solutions in managing, maintaining, processing, and storing authentication data of IoT-enabled assets are an urgent need. From an integration perspective, cloud computing has provided strong support. In contrast, decentralized ledger technology, i.e., blockchain, light-weight cryptosystems, and Artificial Intelligence (AI)-based solutions, are the areas with much more to explore. Finally, we discuss the future research challenges, which will eventually help address the ambiguities for improvement.


Asunto(s)
Cadena de Bloques , Internet de las Cosas , Inteligencia Artificial , Ciudades , Seguridad Computacional
20.
Sensors (Basel) ; 22(2)2022 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-35062490

RESUMEN

Internet of Things (IoT) device security is one of the crucial topics in the field of information security. IoT devices are often protected securely through firmware update. Traditional update methods have their shortcomings, such as bandwidth limitation and being attackers' easy targets. Although many scholars proposed a variety of methods that are based on the blockchain technology to update the firmware, there are still demerits existing in their schemes, including large storage space and centralized stored firmware. In summary, this research proposes a highly secure and efficient protection mechanism that is based on the blockchain technology to improve the above disadvantages. Therefore, this study can reduce the need of storage space and improve system security. The proposed system has good performance in some events, including firmware integrity, security of IoT device connection, system security, and device anonymity. Furthermore, we confirm the high security and practical feasibility of the proposed system by comparing with the existing methods.

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