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1.
BMC Plant Biol ; 24(1): 382, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724900

RESUMO

The highly unique zigzag-shaped stem phenotype in tea plants boasts significant ornamental value and is exceptionally rare. To investigate the genetic mechanism behind this trait, we developed BC1 artificial hybrid populations. Our genetic analysis revealed the zigzag-shaped trait as a qualitative trait. Utilizing whole-genome resequencing, we constructed a high-density genetic map from the BC1 population, incorporating 5,250 SNP markers across 15 linkage groups, covering 3,328.51 cM with an average marker interval distance of 0.68 cM. A quantitative trait locus (QTL) for the zigzag-shaped trait was identified on chromosome 4, within a 61.2 to 97.2 Mb range, accounting for a phenotypic variation explained (PVE) value of 13.62%. Within this QTL, six candidate genes were pinpointed. To better understand their roles, we analyzed gene expression in various tissues and individuals with erect and zigzag-shaped stems. The results implicated CsXTH (CSS0035625) and CsCIPK14 (CSS0044366) as potential key contributors to the zigzag-shaped stem formation. These discoveries lay a robust foundation for future functional genetic mapping and tea plant genetic enhancement.


Assuntos
Camellia sinensis , Caules de Planta , Camellia sinensis/genética , Camellia sinensis/crescimento & desenvolvimento , Mapeamento Cromossômico , Polimorfismo de Nucleotídeo Único , Proteínas de Plantas/genética , Caules de Planta/genética , Caules de Planta/crescimento & desenvolvimento , Genes de Plantas , Locos de Características Quantitativas
2.
Support Care Cancer ; 32(7): 449, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904864

RESUMO

PURPOSE: Patients on oral anticancer agent (OAA) therapies have the autonomy to manage their cancer treatments in home settings. However, patients may not have adequate knowledge, confidence, or ability to effectively manage OAA-related consequences, which can significantly impact their treatment and health outcomes. This study aims to identify the associations between medication beliefs, patient activation, and self-rated health (SRH) among oncology patients taking OAAs and explore the potential mediation effects of patient activation on the relationship between medication beliefs and SRH. METHODS: A secondary data analysis was conducted on cross-sectional data from 114 patients who were diagnosed with breast, colorectal, lung, or prostate cancer. Patients completed a self-reported survey including items of SRH, Beliefs about Medicines Questionnaire (BMQ), and Patient Activation Measure (PAM-13). Descriptive statistics, bivariate correlation, hierarchical multiple linear regression, and mediation analysis were conducted. RESULTS: The results indicate that patients taking OAAs have ambivalent attitudes toward medication. Both medication necessity (r = - 0.27) and concerns (r = - 0.21) were negatively associated with SRH, while patient activation was positively associated with SRH (r = 0.38). Patient activation had a negative association with medication concerns (r = - 0.36) and fully mediated the relationship between medication concerns and SRH in patients taking OAAs (indirect effect = - 0.154, 95% confidence interval, - 0.276 to - 0.060). CONCLUSION: The findings highlight the significance of activating patients to better understand and manage their OAAs. It is crucial for oncology professionals to provide multifaceted interventions to promote patient activation with an effort to mitigate the negative impact of medication beliefs on patient-perceived health outcomes.


Assuntos
Antineoplásicos , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias , Participação do Paciente , Humanos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Idoso , Neoplasias/tratamento farmacológico , Neoplasias/psicologia , Inquéritos e Questionários , Administração Oral , Participação do Paciente/psicologia , Participação do Paciente/métodos , Autorrelato , Adulto , Idoso de 80 Anos ou mais
3.
Support Care Cancer ; 32(6): 352, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748294

RESUMO

PURPOSE: Oncology patients often struggle to manage their medications and related adverse events during transitions of care. They are expected to take an active role in self-monitoring and timely reporting of their medication safety events or concerns to clinicians. The purpose of this study was to explore the factors influencing oncology patients' willingness to report adverse events or concerns related to their medication after their transitions back home. METHODS: A qualitative interview study was conducted with adult patients with breast, prostate, lung, or colorectal cancer who experienced care transitions within the previous year. A semi-structured interview guide was developed to understand patients' perceptions of reporting mediation-related safety events or concerns from home. All interviews were conducted via phone calls, recorded, and transcribed for thematic data analysis. RESULTS: A total of 41 individuals participated in the interviews. Three main themes and six subthemes emerged, including patients' perceived relationship with clinicians (the quality of communication and trust in clinicians), perceived severity of adverse medication events (perceived severe vs. non-severe events), and patient activation in self-management (self-efficacy in self-management and engagement in monitoring health outcomes). CONCLUSION: The patient-clinician relationship significantly affects patients' reporting behaviors, which can potentially interact with other factors, including the severity of adverse events. It is important to engage oncology patients in medication safety self-reporting from home by enhancing health communication, understanding patients' perceptions of severe events, and promoting patient activation. By addressing these efforts, healthcare providers should adopt a more patient-centered approach to enhance the overall quality and safety of oncological care.


Assuntos
Neoplasias , Pesquisa Qualitativa , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Neoplasias/tratamento farmacológico , Neoplasias/psicologia , Adulto , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/psicologia , Relações Médico-Paciente , Entrevistas como Assunto , Comunicação , Antineoplásicos/efeitos adversos , Idoso de 80 Anos ou mais , Autogestão/métodos , Participação do Paciente/métodos , Participação do Paciente/psicologia
4.
J Med Internet Res ; 26: e47685, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457204

RESUMO

BACKGROUND: Actively engaging patients with cancer and their families in monitoring and reporting medication safety events during care transitions is indispensable for achieving optimal patient safety outcomes. However, existing patient self-reporting systems often cannot address patients' various experiences and concerns regarding medication safety over time. In addition, these systems are usually not designed for patients' just-in-time reporting. There is a significant knowledge gap in understanding the nature, scope, and causes of medication safety events after patients' transition back home because of a lack of patient engagement in self-monitoring and reporting of safety events. The challenges for patients with cancer in adopting digital technologies and engaging in self-reporting medication safety events during transitions of care have not been fully understood. OBJECTIVE: We aim to assess oncology patients' perceptions of medication and communication safety during care transitions and their willingness to use digital technologies for self-reporting medication safety events and to identify factors associated with their technology acceptance. METHODS: A cross-sectional survey study was conducted with adult patients with breast, prostate, lung, or colorectal cancer (N=204) who had experienced care transitions from hospitals or clinics to home in the past 1 year. Surveys were conducted via phone, the internet, or email between December 2021 and August 2022. Participants' perceptions of medication and communication safety and perceived usefulness, ease of use, attitude toward use, and intention to use a technology system to report their medication safety events from home were assessed as outcomes. Potential personal, clinical, and psychosocial factors were analyzed for their associations with participants' technology acceptance through bivariate correlation analyses and multiple logistic regressions. RESULTS: Participants reported strong perceptions of medication and communication safety, positively correlated with medication self-management ability and patient activation. Although most participants perceived a medication safety self-reporting system as useful (158/204, 77.5%) and easy to use (157/204, 77%), had a positive attitude toward use (162/204, 79.4%), and were willing to use such a system (129/204, 63.2%), their technology acceptance was associated with their activation levels (odds ratio [OR] 1.83, 95% CI 1.12-2.98), their perceptions of communication safety (OR 1.64, 95% CI 1.08-2.47), and whether they could receive feedback after self-reporting (OR 3.27, 95% CI 1.37-7.78). CONCLUSIONS: In general, oncology patients were willing to use digital technologies to report their medication events after care transitions back home because of their high concerns regarding medication safety. As informed and activated patients are more likely to have the knowledge and capability to initiate and engage in self-reporting, developing a patient-centered reporting system to empower patients and their families and facilitate safety health communications will help oncology patients in addressing their medication safety concerns, meeting their care needs, and holding promise to improve the quality of cancer care.


Assuntos
Tecnologia Digital , Neoplasias , Adulto , Masculino , Humanos , Estudos Transversais , Transferência de Pacientes , Inquéritos e Questionários , Neoplasias/tratamento farmacológico
5.
Int J Mol Sci ; 25(8)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38674133

RESUMO

The unique zigzag-patterned tea plant is a rare germplasm resource. However, the molecular mechanism behind the formation of zigzag stems remains unclear. To address this, a BC1 genetic population of tea plants with zigzag stems was studied using histological observation and bulked segregant RNA-seq. The analysis revealed 1494 differentially expressed genes (DEGs) between the upright and zigzag stem groups. These DEGs may regulate the transduction and biosynthesis of plant hormones, and the effects on the phenylpropane biosynthesis pathways may cause the accumulation of lignin. Tissue sections further supported this finding, showing differences in cell wall thickness between upright and curved stems, potentially due to lignin accumulation. Additionally, 262 single-nucleotide polymorphisms (SNPs) across 38 genes were identified as key SNPs, and 5 genes related to zigzag stems were identified through homologous gene function annotation. Mutations in these genes may impact auxin distribution and content, resulting in the asymmetric development of vascular bundles in curved stems. In summary, we identified the key genes associated with the tortuous phenotype by using BSR-seq on a BC1 population to minimize genetic background noise.


Assuntos
Camellia sinensis , Regulação da Expressão Gênica de Plantas , Polimorfismo de Nucleotídeo Único , RNA-Seq , Camellia sinensis/genética , Camellia sinensis/metabolismo , Caules de Planta/genética , Caules de Planta/metabolismo , Mutação , Fenótipo , Lignina/metabolismo , Lignina/biossíntese , Transcriptoma/genética , Perfilação da Expressão Gênica/métodos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
6.
Mol Med ; 29(1): 157, 2023 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-37953295

RESUMO

BACKGROUND: Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear. METHODS: In this study, we surgically constructed a mouse MI model using USP38 cardiac conditional knockout (USP38-CKO) and cardiac-specific overexpression (USP38-TG) mice and applied biochemical, histological, electrophysiological characterization and molecular biology to investigate the effects of USP38 on atrial inflammation, fibrosis, and AF and its mechanisms. RESULTS: Our results revealed that USP38-CKO attenuates atrial inflammation, thereby ameliorating fibrosis, and abnormal electrophysiologic properties, and reducing susceptibility to AF on day 7 after MI. USP38-TG showed the opposite effect. Mechanistically, The TAK1/NF-κB signaling pathway in the atria was significantly activated after MI, and phosphorylated TAK1, P65, and IκBα protein expression was significantly upregulated. USP38-CKO inhibited the activation of the TAK1/NF-κB signaling pathway, whereas USP38-TG overactivated the TAK1/NF-κB signaling pathway after MI. USP38 is dependent on the TAK1/NF-κB signaling pathway and regulates atrial inflammation, fibrosis, and arrhythmias after MI to some extent. CONCLUSIONS: USP38 plays an important role in atrial inflammation, fibrosis, and AF susceptibility after MI, providing a promising target for the treatment of AF after MI.


Assuntos
Fibrilação Atrial , Infarto do Miocárdio , Proteases Específicas de Ubiquitina , Animais , Camundongos , Fibrilação Atrial/genética , Fibrilação Atrial/metabolismo , Fibrose , Átrios do Coração/metabolismo , Inflamação/patologia , Infarto do Miocárdio/metabolismo , NF-kappa B/metabolismo , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo
7.
J Transl Med ; 21(1): 737, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37853469

RESUMO

BACKGROUND: BRAF non-V600 mutation occupies a relatively small but critical subset in colorectal cancer (CRC). However, little is known about the biological functions and impacts of BRAF class III mutation in CRC. Here, we aim to explore how D594A mutation impacts on biological behaviors and immune related signatures in murine CRC cells. METHODS: BRAF V600E (class I), G469V (class II) and D594A (class III) mutant cell lines were established based on MC38 cells. The biological behaviors of cells were evaluated in respect of cell growth, cell proliferation, cell apoptosis, cell migration and invasion by the methods of colony-forming assay, CCK-8 assay, Annexin V/PI staining and transwell assay. The concentrations of soluble cytokines were detected by ELISA. The membrane expression of immuno-modulatory molecules and the pattern of tumor infiltrating lymphocyte were evaluated by flow cytometry. The molecular mechanism was explored by RNA sequencing. Immunohistochemistry (IHC) staining was used for the detection of CD8α in tumor tissues. qRT-PCR and western blot were performed to assess the mRNA and protein expression. Anti-PD-L1 treatment and cytokines neutralization experiments were conducted in in vivo models. RESULTS: D594A mutant cells displayed lower grade malignancy characteristics than V600E (class I) and G469V (class II) mutant cells. Meanwhile, D594A mutation led to evident immuno-modulatory features including upregulation of MHC Class I and PD-L1. In vivo experiments displayed that the frequency of infiltrated CD8+ T cells was significantly high within D594A mutant tumors, which may provide potential response to anti-PD-L1 therapy. RNA sequencing analysis showed that D594A mutation led to enhanced expression of ATF3 and THBS1, which thus facilitated CXCL9 and CXCL10 production upon IFN-γ treatment. In addition, CXCL9 or CXCL10 neutralization reduced the infiltration of CD8+ T cells into THBS1-overexpressing tumors. CONCLUSIONS: D594A mutant CRC exhibited lower aggressiveness and immune-activated phenotype. ATF3-THBS1-CXCL9/CXCL10 axis mediated functional CD8+ T cells infiltration into the microenvironment of D594A mutant CRC. Our present study is helpful to define this mutation in CRC and provide important insights in designing effective immunotherapeutic strategies in clinic.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias Colorretais , Animais , Camundongos , Neoplasias Colorretais/patologia , Citocinas/genética , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Microambiente Tumoral
8.
Clin Sci (Lond) ; 137(21): 1665-1681, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37903290

RESUMO

BACKGROUND: The inflammatory response and subsequent ventricular remodeling are key factors contributing to ventricular arrhythmias (VAs) after myocardial infarction (MI). Ubiquitin-specific protease 38 (USP38) is a member of the USP family, but the impact of USP38 in arrhythmia substrate generation after MI remains unclear. This study aimed to determine the role of USP38 in post-MI VAs and its underlying mechanisms. METHODS AND RESULTS: Surgical left descending coronary artery ligation was used to construct MI models. Morphological, biochemical, histological, and electrophysiological studies and molecular analyses were performed after MI on days 3 and 28. We found that the USP38 expression was remarkably increased after MI. Cardiac-conditional USP38 knockout (USP38-CKO) reduces the expression of the inflammatory marker CD68 as well as the inflammatory factors TNF-α and IL-1ß after MI, thereby alleviating advanced cardiac fibrosis, electrical remodeling, ion channel remodeling, and susceptibility to VAs. In contrast, cardiac-specific USP38 overexpression (USP38-TG) showed a significant opposite effect, exacerbating the early inflammatory response and cardiac remodeling after MI. Mechanistically, USP38 knockout inhibited activation of the TAK1/NF-κB signaling pathway after MI, whereas USP38 overexpression enhanced activation of the TAK1/NF-κB signaling pathway after MI. CONCLUSIONS: Our study confirms that USP38-CKO attenuates the inflammatory response, improves ventricular remodeling after myocardial infarction, and reduces susceptibility to malignant VA by inhibiting the activation of the TAK1/NF-κB pathway, with USP38-TG playing an opposing role. These results suggest that USP38 may be an important target for the treatment of cardiac remodeling and arrhythmias after MI.


Assuntos
Infarto do Miocárdio , NF-kappa B , Humanos , Animais , NF-kappa B/metabolismo , Remodelação Ventricular , Infarto do Miocárdio/metabolismo , Coração , Transdução de Sinais , Modelos Animais de Doenças , Proteases Específicas de Ubiquitina
9.
BMC Urol ; 23(1): 31, 2023 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-36870955

RESUMO

BACKGROUND: Prostate artery embolization (PAE) is a relatively safe and effective alternative method for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. The adverse events caused by PAE are primarily mild, including urinary tract infection, acute urinary retention, dysuria, fever, etc. Severe complications, such as nontarget organ embolism syndrome or penile glans ischemic necrosis, are rare. Here, we report a case of severe ischemic necrosis of the glans penis after PAE and review the literature. CASE PRESENTATION: An 86-year-old male patient was admitted to the hospital due to progressive dysuria with gross hematuria. The patient underwent placement of a three-way urinary catheter to facilitate continuous bladder flushing, hemostasis, and rehydration. After admission, his hemoglobin decreased to 89 g/L. After an examination, the diagnosis was benign prostatic hyperplasia with bleeding. During communication with the patient regarding treatment, he requested prostate artery embolization due to his advanced age and concomitant disease status. He underwent bilateral prostate artery embolization under local anesthesia. His urine gradually turned clear. However, on the 6th day after embolization, the glans gradually showed ischemic changes. On the 10th day, there was partial necrosis and blackening of the glans. The glans completely healed, and the patient was able to urinate smoothly on the 60th day after local cleaning and debridement, the administration of pain relief, anti-inflammatory and anti-infection agents, and external application of burn ointment. CONCLUSION: Penile glans ischemic necrosis after PAE is rare. The symptoms include pain, congestion, swelling, and cyanosis in the glans.


Assuntos
Próstata , Hiperplasia Prostática , Masculino , Humanos , Idoso de 80 Anos ou mais , Disuria , Artérias , Necrose
10.
Telemed J E Health ; 29(6): 866-874, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36355055

RESUMO

Purpose: To describe cancer survivors' use of electronic communication (e-communication) with clinicians and identify factors associated with their use, including the COVID-19 pandemic. Methods: Secondary analysis included cancer survivors (N = 1,482) from the combined Health Information National Trends Survey HINTS 5 Cycle 3 and Cycle 4. Survivors' use of e-communication was defined by at least one of four e-communication use behaviors in the past 12 months. Bivariate analysis and logistic regression were conducted to examine factors associated with e-communication use. All analyses considered the complex survey design using the jackknife replication method. Results: The prevalence of e-communication use was 64% among cancer survivors. The overall e-communication use slightly increased after the start of the COVID-19 pandemic (63% vs. 64%, p = 0.79). Older adults (≥65 years old) were less likely to use e-communication (odds ratio [OR] = 0.55; 95% confidence interval [CI], 0.36-0.86); survivors who were white (OR = 2.30; 95% CI, 1.36-3.86), living in a metro area (OR = 2.47; 95% CI, 1.44-4.27), diagnosed with breast cancer (OR = 2.03; 95% CI, 1.06-3.88), seeking cancer-related information previously (OR = 2.89; 95% CI, 1.83-4.58), or having a regular health care provider (OR = 2.07,; 95% CI, 1.10-3.88) were more likely to use e-communication. The start of the COVID-19 pandemic was marginally associated with the increased e-communication use (p = 0.053) when other variables were controlled. Conclusion: This nationally representative survey analysis has identified disparities in e-communication use among cancer survivors and revealed the potential increase in e-communication use under the impact of the COVID-19 pandemic. Additional support is clearly warranted for those older, nonwhite, living in rural areas, or without a regular provider, to promote their e-communication use for the delivery of optimal and high-quality cancer care.


Assuntos
Neoplasias da Mama , COVID-19 , Sobreviventes de Câncer , Neoplasias , Humanos , Idoso , Feminino , Pandemias , COVID-19/epidemiologia , Comunicação , Neoplasias/epidemiologia , Neoplasias/terapia , Eletrônica
11.
Pharm Biol ; 61(1): 155-164, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36604840

RESUMO

CONTEXT: Salvia miltiorrhizae Bunge (Lamiaceae) is a traditional Chinese medicine (TCM) for the treatment of 'thoracic obstruction'. Transient receptor potential canonical channel 1 (TRPC1) is a important target for myocardial injury treatment. OBJECTIVE: This work screens the active component acting on TRPC1 from Salvia miltiorrhizae. MATERIALS AND METHODS: TCM Systems Pharmacology Database and Analysis Platform (TCMSP) was used to retrieve Salvia miltiorrhiza compounds for preliminary screening by referring to Lipinski's rule of five. Then, the compound group was comprehensively scored by AutoDock Vina based on TRPC1 protein. Surface plasmon resonance (SPR) was used to determine the affinity of the optimal compound to TRPC1 protein. Western blot assay was carried out to observe the effect of the optimal compound on TRPC1 protein expression in HL-1 cells, and Fura-2/AM detection was carried out to observe the effect of the optimal compound on calcium influx in HEK293 cells. RESULTS: Twenty compounds with relatively good characteristic parameters were determined from 202 compounds of Salvia miltiorrhiza. Rosmarinic acid (RosA) was obtained based on the molecular docking scoring function. RosA had a high binding affinity to TRPC1 protein (KD value = 1.27 µM). RosA (50 µM) could reduce the protein levels (417.1%) of TRPC1 after oxygen-glucose deprivation/reperfusion (OGD/R) in HL-1 cells and it could inhibit TRPC1-mediated Ca2+ influx injury (0.07 ΔRatio340/380) in HEK293 cells. DISCUSSION AND CONCLUSIONS: We obtained the potential active component RosA acting on TRPC1 from Salvia miltiorrhizae, and we speculate that RosA may be a promising clinical candidate for myocardial injury therapy.


Assuntos
Salvia miltiorrhiza , Humanos , Salvia miltiorrhiza/química , Simulação de Acoplamento Molecular , Células HEK293 , Cinamatos/farmacologia , Ácido Rosmarínico
12.
Int J Cancer ; 151(11): 1997-2003, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-35723079

RESUMO

Myosteatosis is a novel imaging biomarker for survival in gynecological cancer patients; however, the evidence is inconsistent. This meta-analysis aims to investigate the impact of myosteatosis on overall survival in the gynecological oncology setting. Three databases (PubMed, EMBASE and Web of Science) were systematically searched for relevant literature up to October 30, 2021. A random-effects model was used to evaluate the predictive effect of myosteatosis on overall survival in the gynecological cancer population. The Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies. Trial sequential analysis was used to control the risk of random errors. Twelve studies with a total of 2519 patients were included. Myosteatosis was associated with a 50% increased mortality risk (HR 1.50, 95% CI 1.24-1.82, P < .001) in gynecological cancer patients. Subgroup analyses stratified by study design, statistical model, treatment, sample size and stage confirmed the predictive value of myosteatosis on survival. However, the prognostic ability of myosteatosis only was held in the American and European populations but lost in Asians. Additionally, myosteatosis was not associated with the increased mortality in endometrial and cervical cancers, except for ovarian cancers. Overall, myosteatosis is a powerful predictor of reduced overall survival in gynecological cancer patients.


Assuntos
Neoplasias dos Genitais Femininos , Neoplasias Ovarianas , Feminino , Neoplasias dos Genitais Femininos/complicações , Humanos , Prognóstico
13.
Microb Pathog ; 162: 105335, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34861347

RESUMO

Protein-based subunit vaccine against tuberculosis (TB) is regarded as safer but with lower immunogenicity. To investigate effective adjuvant to improve the immunogenicity of TB subunit vaccine, we modified ploy(I:C) onto PLGA-PEG copolymer nanoparticle with polydopamine to produce a new nanoparticle adjuvant named "PLGA-PEG-poly(I:C)" (NP). M. tuberculosis fusion proteins Mtb10.4-HspX and ESAT-6-Rv2626c (M4) were encapsulated in the nanoparticles to produce the NP/M4 subunit vaccine. The PLGA-PEG/M4 nanoparticle was 200.21 ± 1.07 nm in diameter, and the polydispersity index (PDI) was 0.127 ± 0.02. Following modification with poly(I:C) by polydopamine, the NP/M4 was administered to C57BL/6 female mice intranasally and the immune responses were evaluated. The NP/M4 significantly induced antigen-specific CD4+ T cells proliferation, IL-2 and IFN-γ production. In addition, the NP/M4 could promote the production of antigen-specific IgG, IgG1, IgG2c in serum, and sIgA in lung washings. Overall, our results indicated that the NP would be a potential TB subunit vaccine adjuvant with the ability to induce strong Th1-type cell-mediated immunity and humoral immune responses.


Assuntos
Mycobacterium tuberculosis , Nanopartículas , Adjuvantes Imunológicos , Adjuvantes de Vacinas , Animais , Antígenos de Bactérias , Feminino , Imunidade Humoral , Camundongos , Camundongos Endogâmicos C57BL
14.
BMC Cancer ; 22(1): 950, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057578

RESUMO

BACKGROUND: More than 60% of cancer cases occur in older adults, and many are treated with oral anticancer agents. Yet, the treatment tolerability in older adults has not been fully understood due to their underrepresentation in oncology clinical trials, creating challenges for treatment decision-making and symptom management. The objective of this study was to investigate the tolerance of capecitabine, an example of oral chemotherapy, among older adults with cancer and explore factors associated with capecitabine-related side effects and treatment changes, to enhance supportive care. METHODS: A secondary analysis used combined data from electronic health records and a pilot study of patient-reported outcomes, with a total of 97 adult patients taking capecitabine during 2016-2017, including older adult patients aged 65 years or older (n = 43). The data extracted included patient socio-demographics, capecitabine information, side effects, and capecitabine treatment changes (dose reductions and dose interruptions). Bivariate correlations, negative binomial regression, and multiple linear regression were conducted for data analysis. RESULTS: Older adults were more likely to experience fatigue (86% vs. 51%, p = .001) and experienced more severe fatigue (ß = 0.44, p = 0.03) and hand-foot syndrome (HFS) (ß = 1.15, p = 0.004) than younger adults. The severity of fatigue and HFS were associated with the number of outpatient medications (ß = 0.06, p = 0.006) and the duration of treatment (ß = 0.50, p = 0.009), respectively. Correlations among side effects presented different patterns between younger and older adults. Although more older adults experienced dose reductions (21% vs. 13%) and dose interruptions (33% vs. 28%) than younger adults, the differences were not statistically different. Female sex, breast cancer diagnosis, capecitabine monotherapy, and severe HFS were found to be associated with dose reductions (p-values < 0.05). CONCLUSIONS: Older adults were less likely to tolerate capecitabine treatment and had different co-occurring side effects compared to younger adults. While dose reductions are common among older adults, age 65 years or older may not be an independent factor of treatment changes. Other socio-demographic and clinical factors may be more likely to be associated. Future studies can be conducted to further explore older adults' tolerance to a variety of oral anticancer agents to generate more evidence to support optimal treatment decision-making and symptom management.


Assuntos
Antineoplásicos , Neoplasias da Mama , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Síndrome Mão-Pé , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Capecitabina/efeitos adversos , Registros Eletrônicos de Saúde , Fadiga/induzido quimicamente , Feminino , Fluoruracila/uso terapêutico , Humanos , Medidas de Resultados Relatados pelo Paciente , Projetos Piloto
15.
J Med Internet Res ; 23(10): e27261, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-34637393

RESUMO

BACKGROUND: Health care organizations (HCOs) adopt strategies (eg. physical distancing) to protect clinicians and patients in intensive care units (ICUs) during the COVID-19 pandemic. Many care activities physically performed before the COVID-19 pandemic have transitioned to virtual systems during the pandemic. These transitions can interfere with collaboration structures in the ICU, which may impact clinical outcomes. Understanding the differences can help HCOs identify challenges when transitioning physical collaboration to the virtual setting in the post-COVID-19 era. OBJECTIVE: This study aims to leverage network analysis to determine the changes in neonatal ICU (NICU) collaboration structures from the pre- to the intra-COVID-19 era. METHODS: In this retrospective study, we applied network analysis to the utilization of electronic health records (EHRs) of 712 critically ill neonates (pre-COVID-19, n=386; intra-COVID-19, n=326, excluding those with COVID-19) admitted to the NICU of Vanderbilt University Medical Center between September 1, 2019, and June 30, 2020, to assess collaboration between clinicians. We characterized pre-COVID-19 as the period of September-December 2019 and intra-COVID-19 as the period of March-June 2020. These 2 groups were compared using patients' clinical characteristics, including age, sex, race, length of stay (LOS), and discharge dispositions. We leveraged the clinicians' actions committed to the patients' EHRs to measure clinician-clinician connections. We characterized a collaboration relationship (tie) between 2 clinicians as actioning EHRs of the same patient within the same day. On defining collaboration relationship, we built pre- and intra-COVID-19 networks. We used 3 sociometric measurements, including eigenvector centrality, eccentricity, and betweenness, to quantify a clinician's leadership, collaboration difficulty, and broad skill sets in a network, respectively. We assessed the extent to which the eigenvector centrality, eccentricity, and betweenness of clinicians in the 2 networks are statistically different, using Mann-Whitney U tests (95% CI). RESULTS: Collaboration difficulty increased from the pre- to intra-COVID-19 periods (median eccentricity: 3 vs 4; P<.001). Nurses had reduced leadership (median eigenvector centrality: 0.183 vs 0.087; P<.001), and neonatologists with broader skill sets cared for more patients in the NICU structure during the pandemic (median betweenness centrality: 0.0001 vs 0.005; P<.001). The pre- and intra-COVID-19 patient groups shared similar distributions in sex (~0 difference), race (4% difference in White, and 3% difference in African American), LOS (interquartile range difference in 1.5 days), and discharge dispositions (~0 difference in home, 2% difference in expired, and 2% difference in others). There were no significant differences in the patient demographics and outcomes between the 2 groups. CONCLUSIONS: Management of NICU-admitted patients typically requires multidisciplinary care teams. Understanding collaboration structures can provide fine-grained evidence to potentially refine or optimize existing teamwork in the NICU.


Assuntos
COVID-19 , Unidades de Terapia Intensiva Neonatal , Humanos , Recém-Nascido , Unidades de Terapia Intensiva , Pandemias , Estudos Retrospectivos , SARS-CoV-2
16.
J Med Internet Res ; 23(3): e24638, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33709929

RESUMO

BACKGROUND: Electronic symptom self-reporting systems (e-SRS) have been shown to improve symptoms and survival in patients with cancer. However, patient engagement in using e-SRS for voluntary symptom self-reporting is less optimal. Multiple factors can potentially affect patients' acceptance and engagement in using home-based e-SRS. However, such factors have not been fully explored in cancer populations. OBJECTIVE: The aim of this study is to understand the acceptance and use of home-based e-SRS by patients with cancer and identify associated facilitators and barriers. METHODS: PubMed, CINAHL, Scopus, and PsycINFO (January 2010 to March 2020) were searched using a combination of Medical Subject Headings (MeSH) terms and keywords such as symptom self-reporting, electronic/technology, cancer, and their synonyms. Included studies focused on the use of home-based e-SRS by patients with cancer and their families. Studies on patients' use of e-SRS in clinical settings only were excluded. Of the 3740 papers retrieved, 33 were included in the final review. Factors associated with patient acceptance and use of e-SRS were extracted and synthesized. RESULTS: Most e-SRS were web based (22/33, 66%) or mobile app based (9/33, 27%). The e-SRS initial acceptance, represented by patient enrollment rates, ranged from 40% (22/55) to 100% (100/100). High e-SRS acceptance was rated by 69% (59/85) to 77.6% (337/434) of the patients after they used the system. The e-SRS use, measured by patients' response rates to questionnaires (ranging from 1596/3521, 45.33% to 92%) or system log-on rates (ranging from 4/12, 33% to 99/100, 99%), declined over time in general patterns. Few studies (n=7) reported e-SRS use beyond 6 months, with the response rates ranging from 62% (40/64) to 85.1% (541/636) and the log-on rates ranging from 63.6% (103/162) to 77% (49/64). The availability of compatible devices and technical support, interactive system features, information accessibility, privacy, questionnaire quality, patient physical/psychosocial status, and age were associated with patient acceptance and use of home-based e-SRS. CONCLUSIONS: Acceptance and use of home-based e-SRS by patients with cancer varied significantly across studies, as assessed by a variety of approaches. The lack of access to technology has remained a barrier to e-SRS adoption. Interactive system features and personalized questionnaires may increase patient engagement. More studies are needed to further understand patients' long-term use of home-based e-SRS behavior patterns to develop personalized interventions to support symptom self-management and self-reporting of patients with cancer for optimal health outcomes.


Assuntos
Aplicativos Móveis , Neoplasias , Autogestão , Telemedicina , Eletrônica , Humanos , Neoplasias/terapia , Autorrelato
17.
BMC Surg ; 21(1): 103, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632188

RESUMO

BACKGROUNDS: Pilocytic astrocytomas (PAs) are World Health Organization (WHO) grade I tumors, which are relatively common, and are benign lesions in children. PAs could originate from the cerebellum, optic pathways, and third ventricular/hypothalamic region. Traditional various transcranial routes are used for hypothalamic PAs (HPAs). However, there are few studies on hypothalamic PAs treated through the endoscopic endonasal approach (EEA). This study reports the preliminary experience of the investigators and results with HPAs via expanded EEAs. METHODS: All patients with HPAs, undergone EEA in our hospital from 2017 to 2019, were retrospectively reviewed. The demographic data, clinical symptoms, complications, skull base reconstruction, prognosis, and endocrinological data were all recorded and analyzed in detail. RESULTS: Finally, five female patients were enrolled. The average age of patients was 28.6 ± 14.0. All patients had complaints about their menstrual disorder. One patient had severe bilateral visual impairment. Furthermore, only one patient suffered from severe headache due to acute hydrocephalus, although there were four patients with headache or dizziness. Four cases achieved gross-total resection, and one patient achieved subtotal resection. Furthermore, there was visual improvement in one patient (case 5), and postoperative worsening of vision in one patient (case 4). However, only one patient had postoperative intracranial infection. None of the patients experienced a postoperative CSF leak, and in situ bone flap (ISBF) techniques were used for two cases for skull base repair. In particular, ISBF combined with free middle turbinate mucosal flap was used for case 5. After three years of follow-up, three patients are still alive, two patients had no neurological or visual symptoms, or tumor recurrence, and one patient had severe hypothalamic dysfunction. Unfortunately, one patient died of severe postoperative hypothalamus reaction, which presented with coma, high fever, diabetes insipidus, hypernatremia and intracranial infection. The other patient died of recurrent severe pancreatitis at one year after the operation. CONCLUSION: Although the data is still very limited and preliminary, EEA provides a direct approach to HPAs with acceptable prognosis in terms of tumor resection, endocrinological and visual outcomes. ISBF technique is safe and reliable for skull base reconstruction.


Assuntos
Astrocitoma , Hipotálamo , Cirurgia Endoscópica por Orifício Natural , Adulto , Astrocitoma/cirurgia , Feminino , Humanos , Hipotálamo/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
18.
Sensors (Basel) ; 21(11)2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067296

RESUMO

In multi-target tracking, the sequential Monte Carlo probability hypothesis density (SMC-PHD) filter is a practical algorithm. Influenced by outliers under unknown heavy-tailed measurement noise, the SMC-PHD filter suffers severe performance degradation. In this paper, a robust SMC-PHD (RSMC-PHD) filter is proposed. In the proposed filter, Student-t distribution is introduced to describe the unknown heavy-tailed measurement noise where the degrees of freedom (DOF) and the scale matrix of the Student-t distribution are respectively modeled as a Gamma distribution and an inverse Wishart distribution. Furthermore, the variational Bayesian (VB) technique is employed to infer the unknown DOF and scale matrix parameters while the recursion estimation framework of the RSMC-PHD filter is derived. In addition, considering that the introduced Student- t distribution might lead to an overestimation of the target number, a strategy is applied to modify the updated weight of each particle. Simulation results demonstrate that the proposed filter is effective with unknown heavy-tailed measurement noise.

19.
Pharm Biol ; 59(1): 222-231, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33600735

RESUMO

CONTEXT: Rosmarinic acid (RosA), a natural poly-phenolic compound isolated from a variety of Labiatae herbs, has been reported to have a range of biological effects. OBJECTIVE: To investigate the cardioprotective effects of RosA against myocardial ischaemia/reperfusion (I/R) injury. MATERIALS AND METHODS: Male C57BL/6J mice were given RosA (100 mg/kg) via intragastric administration. After 1 week of administration, the mice were subjected to 30 min/24 h myocardial I/R injury. The mice were randomly subdivided into 4 groups: Vehicle, RosA, Vehicle + I/R, and RosA + I/R. Infarct size (IS), cardiac function (including EF, FS), histopathology, serum enzyme activities, ROS changes, cis aconitase (ACO) activity, and specific mRNA and protein levels were assessed in vivo. HL-1 cells were pre-treated with or without RosA (50 µM), followed by stimulation with 9 h/6 h of oxygen and glucose deprivation/re-oxygenation (OGD/R). The cells were randomly subdivided into 4 groups: Vehicle, RosA, Vehicle + OGD/R, and RosA + OGD/R. Lactate dehydrogenase (LDH) levels, ACO activity, ROS changes and protein levels were measured in vitro. RESULTS: Treatment with RosA reduced the following indicators in vivo (p < 0.05): (1) IS (14.5%); (2) EF (-23.4%) and FS (-18.4%); (3) the myocardial injury enzymes CK-MB (20.8 ng/mL) and cTnI (7.7 ng/mL); (4) DHE-ROS: (94.1%); (5) ACO activity (-2.1 mU/mg protein); (6) ogdh mRNA level (122.9%); and (7) OGDH protein level (69.9%). Moreover, treatment with RosA attenuated the following indicators in vitro (p < 0.05): (1) LDH level (191 U/L); (2) DHE-ROS: (165.2%); (3) ACO activity (-3.2 mU/mg protein); (4) ogdh mRNA level (70.0%); and (5) OGDH (110.1%), p-IκB-a (56.8%), and p-NF-κB (57.7%) protein levels. CONCLUSIONS: RosA has the potential to treat myocardial I/R injury with potential application in the clinic.


Assuntos
Cardiotônicos/farmacologia , Cinamatos/farmacologia , Depsídeos/farmacologia , Inflamação/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Inflamação/patologia , L-Lactato Desidrogenase/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/fisiopatologia , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ácido Rosmarínico
20.
J Biomed Inform ; 110: 103556, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32916305

RESUMO

OBJECTIVE: The use of poorly designed and improperly implemented health information technology (HIT) may compound risks because it can disrupt established work patterns and encourage workarounds. Analyzing and learning from HIT events could reduce the risks and improve safety but are limited by accessible HIT event reports. In this study, we propose a hybrid deep learning model to identify HIT event reports from the FDA resource and thus establish the first publicly accessible database for HIT event reports. MATERIALS AND METHODS: 6994 samples (3521 HIT and 3473 non-HIT events) extracted from the FDA MAUDE database were employed to assess nine individual and 120 hybrid models on the task of HIT identification. The optimal model was evaluated on an independent dataset prior to its application for establishing the HIT event database. RESULTS: The hybrid model consisting of logistic regression, CNN, and Hierarchical RNN (ACC = 0.903, AUC = 0.954, F1 score = 0.876) is superior to all the other models. The causes of errors include lack of root cause (72.3%), short descriptions (19.7%), and model undertrained (8.0%). The accuracy of the hybrid model on an independent dataset is reported as 0.862. We applied the optimal model to the entire MAUDE database (1991-2018) and generated an HIT event database with 48,997 reports. CONCLUSION: The first HIT event database contains 48,997 reports with an annual growth rate of 10% (~5000 reports). The strategy of HIT event identification and establishment of the database could help healthcare professionals describe, understand, integrate the events and propose solutions in the context of a fuller spectrum of HIT events.


Assuntos
Aprendizado Profundo , Informática Médica , Tecnologia Biomédica , Bases de Dados Factuais , Relatório de Pesquisa
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