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The influenza A virus (IAV) consists of 8 single-stranded, negative-sense viral RNA (vRNA) segments. After infection, vRNA is transcribed, replicated, and wrapped by viral nucleoprotein (NP) to form viral ribonucleoprotein (vRNP). The transcription, replication, and nuclear export of the viral genome are regulated by the IAV protein, NS2, which is translated from spliced mRNA transcribed from viral NS vRNA. This splicing is inefficient, explaining why NS2 is present in low abundance after IAV infection. The levels of NS2 and its subsequent accumulation are thought to influence viral RNA replication and vRNP nuclear export. Here we show that NS2 is ubiquitinated at the K64 and K88 residues by K48-linked and K63-linked polyubiquitin (polyUb) chains, leading to the degradation of NS2 by the proteasome. Additionally, we show that a host deubiquitinase, OTUB1, can remove polyUb chains conjugated to NS2, thereby stabilizing NS2. Accordingly, knock down of OTUB1 by siRNA reduces the nuclear export of vRNP, and reduces the overall production of IAV. These results collectively demonstrate that the levels of NS2 in IAV-infected cells are regulated by a ubiquitination-deubiquitination system involving OTUB1 that is necessary for optimal IAV replication.
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Cisteína Endopeptidases , Vírus da Influenza A , Proteínas não Estruturais Virais , Replicação Viral , Animais , Cães , Humanos , Cisteína Endopeptidases/metabolismo , Cisteína Endopeptidases/genética , Enzimas Desubiquitinantes/metabolismo , Células HEK293 , Vírus da Influenza A/metabolismo , Influenza Humana/metabolismo , Influenza Humana/virologia , RNA Viral/metabolismo , RNA Viral/genética , Ubiquitinação , Proteínas não Estruturais Virais/metabolismo , Proteínas não Estruturais Virais/genética , Replicação Viral/fisiologia , Linhagem Celular , Células Vero , Chlorocebus aethiopsRESUMO
Astragalus polysaccharides (APSs), the compounds extracted from the common herb Astragalus membranaceus, have been extensively studied for their antitumor properties. In this study, we investigated the effect of APS on lung adenocarcinoma A549 cells. The effects of APS and the anti-diabetic drug metformin on apoptosis and ferroptosis were compared. Furthermore, the combination treatment of APS and metformin was also investigated. We found that APS not only reduced the growth of lung cancer cells but also had a synergistic effect with metformin on A549 cells. The study results showed that it may be promising to use APS and metformin as a combination therapy for the treatment of lung adenocarcinoma.
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Neutrophil extracellular traps (NETs) play a role in innate pathogen defense and also trigger B-cell response by providing antigens. NETs have been linked to vaccine-induced thrombotic thrombocytopenia. We postulated a potential link between NET biomarkers, NET-promoting autoantibodies, and adverse events (AEs) after COVID-19 vaccine boosters. Healthy donors (HDs) who received ChAdOx1-S (A), mRNA-1273 (M), or recombinant protein (MVC-COV1901) vaccines at the National Taiwan University Hospital between 2021 and 2022 were recruited. We measured serial NET-associated biomarkers, citrullinated-histone3 (citH3), and myeloperoxidase (MPO)-DNA. Serum citH3 and MPO-DNA were significantly or numerically higher in HDs who reported AEs (n = 100, booster Day 0/Day 30, p = 0.01/p = 0.03 and p = 0.30/p = 0.35, respectively). We also observed a positive correlation between rash occurrence in online diaries and elevated citH3. A linear mixed model also revealed significantly higher citH3 levels in mRNA-1273/ChAdOx1-S recipients than MVC-COV1901 recipients. Significant positive correlations were observed between the ratios of anti-heparin platelet factor 4 and citH3 levels on Booster Day 0 and naïve and between the ratios of anti-NET IgM and citH3 on Booster Day 30/Day 0 in the AA-M and MM-M group, respectively. The increased levels of citH3/MPO-DNA accompanied by NET-promoting autoantibodies suggest a potential connection between mRNA-1273/ChAdOx1-S vaccines and cardiovascular complications. These findings provide insights for risk assessments of future vaccines.
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COVID-19 , Armadilhas Extracelulares , Humanos , Armadilhas Extracelulares/metabolismo , Vacinas contra COVID-19/efeitos adversos , Autoanticorpos , Vacina de mRNA-1273 contra 2019-nCoV , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , COVID-19/prevenção & controle , COVID-19/metabolismo , Biomarcadores , ChAdOx1 nCoV-19 , Vacinação , DNA/metabolismo , AdenoviridaeRESUMO
Multiplexed fluorescence detection has become increasingly important in the fields of biosensing and bioimaging. Although a variety of excitation/detection optical designs and fluorescence unmixing schemes have been proposed to allow for multiplexed imaging, rapid and reliable differentiation and quantification of multiple fluorescent species at each imaging pixel is still challenging. Here we present a pulsed interleaved excitation spectral fluorescence lifetime microscopic (PIE-sFLIM) system that can simultaneously image six fluorescent tags in live cells in a single hyperspectral snapshot. Using an alternating pulsed laser excitation scheme at two different wavelengths and a synchronized 16-channel time-resolved spectral detector, our PIE-sFLIM system can effectively excite multiple fluorophores and collect their emission over a broad spectrum for analysis. Combining our system with the advanced live-cell labeling techniques and the lifetime/spectral phasor analysis, our PIE-sFLIM approach can well unmix the fluorescence of six fluorophores acquired in a single measurement, thus improving the imaging speed in live-specimen investigation.
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Diagnóstico por Imagem , Transferência Ressonante de Energia de Fluorescência , Transferência Ressonante de Energia de Fluorescência/métodos , Corantes FluorescentesRESUMO
PURPOSE: We investigated the volumetric changes in the components of the cholinergic pathway for patients with early mild cognitive impairment (EMCI) and those with late mild cognitive impairment (LMCI). The effect of patients' apolipoprotein 4 (APOE-ε4) allele status on the structural changes were analyzed. METHODS: Structural magnetic resonance imaging data were collected. Patients' demographic information, plasma data, and validated global cognitive composite scores were included. Relevant features were extracted for constructing machine learning models to differentiate between EMCI (n = 312) and LMCI (n = 541) and predict patients' neurocognitive function. The data were analyzed primarily through one-way analysis of variance and two-way analysis of covariance. RESULTS: Considerable differences were observed in cholinergic structural changes between patients with EMCI and LMCI. Cholinergic atrophy was more prominent in the LMCI cohort than in the EMCI cohort (P < 0.05 family-wise error corrected). APOE-ε4 differentially affected cholinergic atrophy in the LMCI and EMCI cohorts. For LMCI cohort, APOE-ε4 carriers exhibited increased brain atrophy (left amygdala: P = 0.001; right amygdala: P = 0.006, and right Ch123, P = 0.032). EMCI and LCMI patients showed distinctive associations of gray matter volumes in cholinergic regions with executive (R2 = 0.063 and 0.030 for EMCI and LMCI, respectively) and language (R2 = 0.095 and 0.042 for EMCI and LMCI, respectively) function. CONCLUSIONS: Our data confirmed significant cholinergic atrophy differences between early and late stages of mild cognitive impairment. The impact of the APOE-ε4 allele on cholinergic atrophy varied between the LMCI and EMCI groups.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Disfunção Cognitiva/patologia , Imageamento por Ressonância Magnética/métodos , Colinérgicos , Apolipoproteínas E , Atrofia , Doença de Alzheimer/patologiaRESUMO
Gender self-identification (transgender) is not permitted in most Asian countries. In Taiwan, individuals recognized as transgender must meet requirements mandated by the Gender Recognition Act. Currently, lifting the requirement for proof of sex-reassignment surgery is pending. The aim of this study was to survey a large sample of Taiwanese to gain a better understanding of the general population's attitudes toward gender self-identification. A self-report survey, entitled "Opinions of Gender Self-Identification," collected demographic information and responses (agree = 1, disagree = 0) to 14 statements about transgender women and women's safety, personal rights, and the law; one statement discussed rights of transgender men to give birth; total scores ranged from 0 to 14. The online survey was distributed to non-government organizations across Taiwan and the Taiwanese islands and was available between April 16 and 30, 2022. Most of the 10,158 respondents were female (77.4%); ages of respondents ranged from 15 to > 65 years. The mean total score was 0.95 ± 2.27, indicating respondents strongly disagreed with support for transgender females; 91.56% disagreed with all statements. Although there were significant differences in scores between parents and non-parents, and those ≤ 35 years versus ≥ 36 years (p < .01), all strongly disagreed with gender self-identification. Given the majority of respondents were females, survey findings should be regarded with caution. Public acceptance of gender self-identification requires support from its residents. Our findings suggest that gender self-identification has not begun to approach even a moderate level of public support among survey respondents.
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Pessoas Transgênero , Humanos , Taiwan , Pessoas Transgênero/psicologia , Pessoas Transgênero/estatística & dados numéricos , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Adolescente , Inquéritos e Questionários , Idoso , Adulto Jovem , Identidade de Gênero , AtitudeRESUMO
OBJECTIVE: To explore the impact on Taiwanese parents and children following an outbreak of the Omicron variant during the COVID-19 pandemic. METHODS: Data were collected following class cancellations mandated by the Ministry of Education due to an outbreak of the Omicron variant of COVID-19 in April 2022. A national parent organization developed self-report survey questionnaire, "Impact of the Pandemic-related School Closures/Class Cancellations" (IPRSCCC), assessed parents' perceived impact of school cancellations on their child/children' and on their adaptation. The online survey was available between May 4 and May 9, 2022, in 20 districts throughout Taiwan. RESULTS: A total of 2126 parents representing 2592 children responded. Total scores on the IPRSCCC were significantly higher for parents of children whose classes were cancelled (n = 891) compared with parents whose children continued in-person classes (n = 1053). Parents perceived the class cancellations of the child/children disrupted daily routine, learning loss and impacted academic motivation. They also reported emotional stress and no time for rest, which were associated with parental burnout. However for these parents, there were no significant differences in scores between parents living in low and high socioeconomic areas. Only the subscale score for disrupted daily routine was significantly higher for fathers, and emotional stress was significantly higher for parents with two, or ≥ 3 children. When academic impacts were examined using national examination scores for 12th grade students, the percent of students with scores of ≤ 6 in English, Chinese, and mathematics was higher in 2022 than in 2020. CONCLUSIONS: Higher IPRSCCC scores for parents of children whose classes were cancelled provides additional evidence of the impact of disruptions of in-person classes due to the COVID-19 pandemic. Examination scores confirmed class cancellations impacted academic performance.
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COVID-19 , Pais , SARS-CoV-2 , Instituições Acadêmicas , Humanos , COVID-19/epidemiologia , Taiwan/epidemiologia , Pais/psicologia , Criança , Masculino , Feminino , Adulto , Adaptação Psicológica , Adolescente , Inquéritos e Questionários , Pandemias , Surtos de DoençasRESUMO
BACKGROUND: Palliative care requires a multidisciplinary team to assist patients and their families to obtain good quality care at the end of life. Typically, community pharmacists have fewer opportunities to provide services for patients with palliative care needs than hospital pharmacists. Moreover, home-based palliative care (HBPC) by pharmacists remains low and there is a lack of research regarding HBPC provided by pharmacists. Therefore, this study sought to understand the views and reflections of community pharmacists in the clinical frontline providing palliative home services. METHODS: Purposive sampling was used to recruit six community pharmacists for one-on-one, in-depth, semi-structured interviews and the data were analysed using thematic analysis. RESULTS: Five major themes emerged: [1] Engagement, [2] Challenge, [3] Mission, [4] Career metamorphosis, and [5] Outlook. The pharmacists described how they engaged in HBPC and faced the challenges. They regarded opioid management as a burden. Moreover, some mentioned that reimbursement for palliative home care is low or non-profitable. They suggested building a platform to exchange advice and legislation adjustments so that they could pass on their experiences to less experienced pharmacists in HBPC. CONCLUSIONS: The involvement of pharmacists is crucial to provide better palliative care. Although the present study was small and might not fully represent the whole situation, the findings could still inform future education, training, and policy planning to promote pharmacists' participation in palliative care to generalise community palliative care.
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Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Cuidados Paliativos , Humanos , Farmacêuticos , Papel Profissional , Atitude do Pessoal de Saúde , Pesquisa QualitativaRESUMO
OBJECTIVES: To determine the location and intensity of the corneal pigmented arc in orthokeratology (ortho-k)-treated children and its relationship with annual axial length (AL) change using Pentacam. METHODS: This retrospective cohort study enrolled children aged 9 to 15 years who had been followed up for at least one year after ortho-k treatment for myopia control. A Pentacam was used to determine the location and intensity of pigmented arc after lens wear. Annual AL changes were further used as the outcome measurement to determine their relationships with the location and intensity of pigmented arc using generalized estimating equations (GEE). RESULTS: In total, 62 eyes from 33 patients (mean age 10.9 years) were included in our final analysis. The mean follow-up time was 30.6 months. The mean annual AL changes were 0.10 mm. Age statistically correlated with annual AL change (GEE, P= 0.033). In addition, the annual AL change was negatively associated with the relative vertical distance of the lowest density of pigmented arc point based on the visual center, pupil center, and corneal thinnest point after adjustment with age ( P =0.005, P =0.004, and P< 0.001, respectively). CONCLUSIONS: Pentacam could be a useful tool for evaluating the location and intensity of the corneal pigmented arc. In addition, there was a negative correlation between the vertical distance of the pigmented arc and annual AL change. These findings may provide important information regarding myopia control, next-generation ortho-k design, and prescription.
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Lentes de Contato , Miopia , Procedimentos Ortoceratológicos , Transtornos da Pigmentação , Criança , Humanos , Estudos Retrospectivos , Córnea , Miopia/terapia , Topografia da Córnea , Refração Ocular , Transtornos da Visão , Comprimento Axial do OlhoRESUMO
ABSTRACT: Myoepithelial carcinomas of soft tissue are rare, and most are malignant. The optimal treatment is surgical excision. The arches of the foot are a composite structure responsible for weight bearing and pressure distribution, so it is a vast challenge in reconstruction. We report a case of reconstruction of the midfoot with a free fibular bone flap and tendon graft. We review the literature to compare various options in foot reconstructions and sort out the outcomes of different bone flaps. The free fibula osteocutaneous flap is the superior choice for midfoot reconstruction owing to its sufficient length, strength, flexible skin paddles, easy-to-withstand osteotomy, and simultaneous tendon graft harvesting.
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Fíbula , Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Humanos , Fíbula/transplante , Procedimentos de Cirurgia Plástica/métodos , Retalhos de Tecido Biológico/transplante , Mioepitelioma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Patients with traumatic brain injuries (TBIs) often experience concurrent facial bone fractures. In 2021, a prediction model with 10 variables was published and precisely predicted concomitant facial fractures in TBI patients. Herein, external validation and simplification of this model was performed. METHODS: Traumatic brain injury patients treated at a major referral trauma center were retrospectively reviewed for 1 year. The original prediction model (published in 2021), which was developed from a rural level II trauma center, was applied for external validation. A new and simplified model from our level I trauma center was developed and backwardly validated by rural level II trauma center data. RESULTS: In total, 313 TBI patients were enrolled; 101 (32.3%) had concomitant facial fractures. When the previous prediction model was applied to the validation cohort, it achieved acceptable discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.713 and good precision, with a Brier score of 0.083. A new and simplified model with 6 variables (age, tooth rupture, epistaxis, facial lesion, eye injury, and intracranial hemorrhage) was created with excellent discrimination (AUC = 0.836) and good precision (Brier score of 0.055). The backward validation of this new model also showed excellent discrimination in the cohort used to develop the original model (AUC = 0.875). CONCLUSION: The original model provides an acceptable and reproducible prediction of concomitant facial fractures among TBI patients. A simplified model with fewer variables and the same accuracy could be applied in the emergency department and at higher- and lower-level trauma centers.
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Lesões Encefálicas Traumáticas , Fraturas Cranianas , Humanos , Estudos Retrospectivos , Fraturas Cranianas/complicações , Fraturas Cranianas/diagnóstico , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico , Curva ROC , Centros de TraumatologiaRESUMO
BACKGROUND: A prediction system for common bile duct (CBD) stones was originally published by the American Society for Gastrointestinal Endoscopy (ASGE) in 2010 and was last revised in 2019. We wanted to investigate its application in an Asian population, who have different etiologies of bile duct stone formation and accessibility to medical service compared to the West. METHODS: This is a single center retrospective study. Patients who received endoscopic ultrasound (EUS) for suspected CBD stones were collected from our endoscopic record system over a 10-year period. The accuracy of the revised ASGE criteria was estimated according to the results of EUS. A minimum follow-up of 6 months was required to detect false negative results. RESULTS: 142 patients were enrolled, 87 (61%) patients had CBD stones. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the revised ASGE criteria for high-risk patients were 69%, 38%, 64%, 44%, and 57%. 36% of the ASGE-defined high-risk patients negative for CBD stones on EUS. The two significant predictors for CBD stone were CBD dilatation (adjusted OR 3.06, 95% C.I. 1.31-7.17, p = 0.010) and ascending cholangitis (adjusted OR 2.28, 95% C.I. 1.01-5.15, p = 0.047). CONCLUSION: ASGE recommends that patients defined as high-risk for choledocholithiasis be considered for direct ERCP without prior need for confirmation imaging. However, our findings indicate a high rate (36%) of patients in that group negative for CBD stones on EUS. Hence, EUS is still be suggested first in selective high-risk patients so that diagnostic ERCP can be avoided in our Asian society.
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Coledocolitíase , Cálculos Biliares , Humanos , Colangiopancreatografia Retrógrada Endoscópica , Estudos Retrospectivos , Endossonografia/métodos , Coledocolitíase/diagnóstico por imagem , Cálculos Biliares/diagnóstico , Endoscopia GastrointestinalRESUMO
BACKGROUND/PURPOSE: Endoscopic stenting at malignant distal duodenum stenosis (MDDS) is challenging because of the duodenal C-loop configuration, the acute angle of the duodenojejunal junction, and the limited length of the endoscope. Few studies have investigated the clinical outcomes of stenting at the distal duodenum. Therefore, this study aimed to investigate the clinical outcomes of treating MDDS with different types of metallic stents. METHODS: From January 2012 to December 2020, fifty-six patients with MDDS who underwent duodenal stenting were enrolled for analysis. Thirty-five patients received uncovered self-expandable metallic stents (UC-SEMS), and twenty-one patients received partially covered self-expandable metallic stents (PC-SEMS). All patients were followed up till death or for 18 months. The clinical success rate, stent dysfunction rate, and stent patency were compared between the groups. Multivariate analysis was conducted to identify factors related to stent dysfunction. RESULTS: The clinical success rates were 85.7 % in both the UC-SEMS and PC-SEMS groups. Stent dysfunction rates (UC-SEMS: 34.3 %, PC-SEMS: 38.1 %, p = 0.773) and the average stent patency (UC-SEMS: 117.2 days, PC-SEMS: 100.0 days, p = 0.576) were not statistically different between the groups. Multivariate analysis disclosed the age ≥65 years was significantly related to stent dysfunction (odds ratio: 4.78, p = 0.031). CONCLUSION: Both UC-SEMS and PC-SEMS are safe and effective treatment options for MDDS. However, stent dysfunction remains a significant issue to overcome, particularly in the elderly. Further research is needed to explore novel strategies that can improve the effectiveness of stent placement and reduce the risk of stent dysfunction.
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Obstrução Duodenal , Stents Metálicos Autoexpansíveis , Humanos , Feminino , Masculino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Obstrução Duodenal/etiologia , Obstrução Duodenal/cirurgia , Obstrução Duodenal/terapia , Resultado do Tratamento , Idoso de 80 Anos ou mais , Stents/efeitos adversos , Constrição Patológica , Duodeno/cirurgia , TaiwanRESUMO
OBJECTIVES: This consensus was developed by the Asian EUS Group (AEG), who aimed to formulate a set of practice guidelines addressing various aspects of endoscopic ultrasound-guided tissue acquisition (EUS-TA). METHODS: The AEG initiated the development of consensus statements and formed an expert panel comprising surgeons, gastroenterologists, and pathologists. Three online consensus meetings were conducted to consolidate the statements and votes. The statements were presented and discussed in the first two consensus meetings and revised according to comments. Final voting was conducted at a third consensus meeting. The Grading of Recommendations, Assessment, Development, and Evaluation system was adopted to define the strength of the recommendations and quality of evidence. RESULTS: A total of 20 clinical questions and statements regarding EUS-TA were formulated. The committee recommended that fine-needle biopsy (FNB) needles be preferred over conventional fine-needle aspiration (FNA) needles for EUS-TA of subepithelial lesions. For solid pancreatic masses, rapid on-site evaluation is not routinely recommended when FNB needles are used. For dedicated FNB needles, fork-tip and Franseen-tip needles have essentially equivalent performance. CONCLUSION: This consensus provides guidance for EUS-TA, thereby enhancing the quality of EUS-TA.
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Consenso , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Humanos , Ásia , Endossonografia , Guias de Prática Clínica como AssuntoRESUMO
This study applied machine learning for the early prediction of 30-day mortality at sepsis diagnosis time in critically ill patients. Retrospective study using data collected from the Medical Information Mart for Intensive Care IV database. The data of the patient cohort was divided on the basis of the year of hospitalization, into training (2008-2013), validation (2014-2016), and testing (2017-2019) datasets. 24,377 patients with the sepsis diagnosis time < 24 h after intensive care unit (ICU) admission were included. A gradient boosting tree-based algorithm (XGBoost) was used for training the machine learning model to predict 30-day mortality at sepsis diagnosis time in critically ill patients. Model performance was measured in both discrimination and calibration aspects. The model was interpreted using the SHapley Additive exPlanations (SHAP) module. The 30-day mortality rate of the testing dataset was 17.9%, and 39 features were selected for the machine learning model. Model performance on the testing dataset achieved an area under the receiver operating characteristic curve (AUROC) of 0.853 (95% CI 0.837-0.868) and an area under the precision-recall curves of 0.581 (95% CI 0.541-0.619). The calibration plot for the model revealed a slope of 1.03 (95% CI 0.94-1.12) and intercept of 0.14 (95% CI 0.04-0.25). The SHAP revealed the top three most significant features, namely age, increased red blood cell distribution width, and respiratory rate. Our study demonstrated the feasibility of using the interpretable machine learning model to predict mortality at sepsis diagnosis time.
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Estado Terminal , Sepse , Humanos , Estudos Retrospectivos , Sepse/diagnóstico , Algoritmos , Aprendizado de MáquinaRESUMO
A-to-I RNA editing, catalyzed by the ADAR protein family, significantly contributes to the diversity and adaptability of mammalian RNA signatures, aligning with developmental and physiological needs. Yet, the functions of many editing sites are still to be defined. The Unc80 gene stands out in this context due to its brain-specific expression and the evolutionary conservation of its codon-altering editing event. The precise biological functions of Unc80 and its editing, however, are still largely undefined. In this study, we first demonstrated that Unc80 editing occurs in an ADAR2-dependent manner and is exclusive to the brain. By employing the CRISPR/Cas9 system to generate Unc80 knock-in mouse models that replicate the natural editing variations, our findings revealed that mice with the "gain-of-editing" variant (Unc80G/G) exhibit heightened basal neuronal activity in critical olfactory regions, compared to the "loss-of-editing" (Unc80S/S) counterparts. Moreover, an increase in glutamate levels was observed in the olfactory bulbs of Unc80G/G mice, indicating altered neurotransmitter dynamics. Behavioral analysis of odor detection revealed distinctive responses to novel odors-both Unc80 deficient (Unc80+/-) and Unc80S/S mice demonstrated prolonged exploration times and heightened dishabituation responses. Further elucidating the olfactory connection of Unc80 editing, transcriptomic analysis of the olfactory bulb identified significant alterations in gene expression that corroborate the behavioral and physiological findings. Collectively, our research advances the understanding of Unc80's neurophysiological functions and the impact of its editing on the olfactory sensory system, shedding light on the intricate molecular underpinnings of olfactory perception and neuronal activity.
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Adenosina Desaminase , Percepção Olfatória , Edição de RNA , Animais , Camundongos , Percepção Olfatória/fisiologia , Adenosina Desaminase/metabolismo , Adenosina Desaminase/genética , Bulbo Olfatório/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Neurônios/metabolismo , Sistemas CRISPR-Cas , Masculino , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismoRESUMO
Platelets assume a pivotal role in the pathogenesis of cardiovascular diseases (CVDs), emphasizing their significance in disease progression. Consequently, addressing CVDs necessitates a targeted approach focused on mitigating platelet activation. Eugenol, predominantly derived from clove oil, is recognized for its antibacterial, anticancer, and anti-inflammatory properties, rendering it a valuable medicinal agent. This investigation delves into the intricate mechanisms through which eugenol influences human platelets. At a low concentration of 2 µM, eugenol demonstrates inhibition of collagen and arachidonic acid (AA)-induced platelet aggregation. Notably, thrombin and U46619 remain unaffected by eugenol. Its modulatory effects extend to ATP release, P-selectin expression, and intracellular calcium levels ([Ca2+]i). Eugenol significantly inhibits various signaling cascades, including phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3ß, mitogen-activated protein kinases, and cytosolic phospholipase A2 (cPLA2)/thromboxane A2 (TxA2) formation induced by collagen. Eugenol selectively inhibited cPLA2/TxA2 phosphorylation induced by AA, not affecting p38 MAPK. In ADP-treated mice, eugenol reduced occluded lung vessels by platelet thrombi without extending bleeding time. In conclusion, eugenol exerts a potent inhibitory effect on platelet activation, achieved through the inhibition of the PLCγ2-PKC and cPLA2-TxA2 cascade, consequently suppressing platelet aggregation. These findings underscore the potential therapeutic applications of eugenol in CVDs.
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Eugenol , Embolia Pulmonar , Humanos , Camundongos , Animais , Eugenol/farmacologia , Eugenol/uso terapêutico , Eugenol/metabolismo , Fosfolipase C gama/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Modelos Animais de Doenças , Ativação Plaquetária , Agregação Plaquetária , Plaquetas/metabolismo , Fosforilação , Proteína Quinase C/metabolismo , Tromboxano A2/metabolismo , Colágeno/metabolismo , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/metabolismo , Fosfolipases A2 Citosólicas/metabolismoRESUMO
OBJECTIVE: This study aimed to explore the impact of physical activity on health among older adults in urban and rural areas in Taiwan. METHODS: This study employed a cross-sectional design and data were analyzed from 2015 to 2019 from the Hualien County Health Bureau. Participants were divided into urban (n = 4780) and rural groups (n = 4983), and logistic regression models were employed to examine how physical activity relates to their health condition in urban and rural older adults. RESULTS: Results indicated lower physical activity levels and higher unhealthy behavior rate in rural older adults compared to their urban counterparts. Rural older adults had higher rates of cardiovascular diseases and diabetes but lower rates of mental illness. Physical activity demonstrated greater physical health benefits for urban older adults than rural older people. Conversely, rural individuals who engaged in physical activity 150 min/week exhibited greater mental health benefits than their urban counterparts. CONCLUSIONS: Physical activity offers significant mental health benefits for both urban and rural older adults; however, notable improvements in physical health among urban older adults was found. If in the presence of unhealthy behaviors, regular physical activity may not effectively prevent chronic diseases. It is crucial to promote physical activity and healthy behaviors in rural areas.
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BACKGROUND: Interdisciplinary collaboration is known to foster professional innovation and enhance student learning across different domains. However, the research on the effectiveness of integration of interdisciplinary learning in pediatric nursing education is limited. Therefore, this study aimed to examine the effectiveness of integrating game-based learning, an interdisciplinary approach to teaching, into pediatric nursing education's play courses. METHODS: We used a mixed methods study with pre-test/post-test quantitative analyses and a descriptive qualitative analysis of students' reflection journals. Data were collected between August 2019 and July 2020 to gauge course effectiveness. Quantitative data obtained from the questionnaires were analyzed using a t-test, correlation, and regression analysis. Qualitative data using students' reflective journals were collected and analyzed using content analysis. One hundred and three second-year nursing students enrolled in a four-year nursing program. Nursing students attended classes in university classrooms and served learning in a kindergarten or hospital in Northern Taiwan. RESULTS: The subscales of Students' Learning Outcome in knowledge, abilities, and attitudes showed significantly higher mean post-test scores compared to pre-test scores: 26.15 (SD = 3.35) vs. 16.82 (SD = 4.49), p < .001; 18.03 (SD = 2.13) vs. 11.43 (SD = 2.95), p < .001; and 12.90 (SD = 2.12) vs. 8.72 (SD = 2.52), p < .001. Furthermore, scores on the Service-Learning Abilities Scale indicated a significant increase in communication, problem-solving, knowledge application, and cross-cultural competence. Integrating instruction to improve problem-solving skills and knowledge application predicts student learning outcomes. Qualitative findings revealed nursing students' reflections on integrating different learning areas, communication, problem-solving, and practical knowledge skills. CONCLUSIONS: Integration of interdisciplinary learning effectively stimulates learning among nursing students and enhances their knowledge, abilities, and attitudes toward therapeutic play, benefiting children's health. Our findings demonstrate that integration of interdisciplinary learning significantly enhances nursing students' healthcare-giving competence, particularly in communication, problem-solving, knowledge application, and cross-cultural competence as measured by the Service-Learning Scale. Integrating social service with integration of interdisciplinary learning exposes nursing students to diverse challenges and needs, thereby enhancing their communication skills, knowledge application, and problem-solving abilities. Nursing students can blend knowledge and skills through integrated learning, which is crucial for nursing career preparation. TRIAL REGISTRATION: N/A. It was a survey on educational activities.
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BACKGROUND: The pathophysiology of the reversible cerebral vasoconstriction syndrome (RCVS) remains enigmatic and the role of glymphatics in RCVS pathophysiology has not been evaluated. We aimed to investigate RCVS glymphatic dynamics and its clinical correlates. METHODS: We prospectively evaluated the glymphatic function in RCVS patients, with RCVS subjects and healthy controls (HCs) recruited between August 2020 and November 2023, by calculating diffusion-tensor imaging along the perivascular space (DTI-ALPS) index under a 3-T MRI. Clinical and vascular (transcranial color-coded duplex sonography) investigations were conducted in RCVS subjects. RCVS participants were separated into acute (≤ 30 days) and remission (≥ 90 days) groups by disease onset to MRI interval. The time-trend, acute stage and longitudinal analyses of the DTI-ALPS index were conducted. Correlations between DTI-ALPS index and vascular and clinical parameters were performed. Bonferroni correction was applied to vascular investigations (q = 0.05/11). RESULTS: A total of 138 RCVS patients (mean age, 46.8 years ± 11.8; 128 women) and 42 HCs (mean age, 46.0 years ± 4.5; 35 women) were evaluated. Acute RCVS demonstrated lower DTI-ALPS index than HCs (p < 0.001) and remission RCVS (p < 0.001). A continuously increasing DTI-ALPS trend after disease onset was demonstrated. The DTI-ALPS was lower when the internal carotid arteries resistance index and six-item Headache Impact test scores were higher. In contrast, during 50-100 days after disease onset, the DTI-ALPS index was higher when the middle cerebral artery flow velocity was higher. CONCLUSIONS: Glymphatic function in patients with RCVS exhibited a unique dynamic evolution that was temporally coupled to different vascular indices and headache-related disabilities along the disease course. These findings may provide novel insights into the complex interactions between glymphatic transport, vasomotor control and pain modulation.