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1.
Nanomaterials (Basel) ; 11(10)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34684912

RESUMO

Recently, the effects of nanoplastics (NPs) on aquatic organisms have attracted much attention; however, research on the toxicity of NPs to microalgae has been insufficient. In the present study, the effects of polystyrene nanoplastics (nano-PS, 50 nm) on growth inhibition, chlorophyll content, oxidative stress, and algal toxin production of the marine toxigenic dinoflagellate Amphidinium carterae Hulburt were investigated. Chlorophyll synthesis was promoted by nano-PS on day 2 but was inhibited on day 4; high concentrations of nano-PS (≥50 mg/L) significantly inhibited the growth of A. carterae. Moreover, despite the combined effect of superoxide dismutase (SOD) and glutathione (GSH), high reactive oxygen species (ROS) level and malondialdehyde (MDA) content were still induced by nano-PS (≥50 mg/L), indicating severe lipid peroxidation. In addition, the contents of extracellular and intracellular hemolytic toxins in nano-PS groups were significantly higher than those in control groups on days 2 and 8, except that those of extracellular hemolytic toxins in the 100 mg/L nano-PS group decreased on day 8 because of severe adsorption of hemolytic toxins to the nano-PS. Hence, the effects of nano-PS on A. carterae are closely linked to nano-PS concentration and surface properties and exposure time. These findings provide a deep understanding of the complex effects of NPs on toxigenic microalgae and present valuable data for assessing their environmental risks.

2.
Environ Sci Technol ; 55(21): 14979-14989, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34677955

RESUMO

Nitrogen (N) fixation in soils is closely linked to microbially mediated molybdenum (Mo) cycling. Therefore, elucidating the mechanisms and factors that affect Mo bioavailability is crucial for understanding N fixation. Here, we demonstrate that long-term (26 years) manure fertilization increased microbial diversity and content of short-range ordered iron (oxyhydr)oxides that raised Mo bioavailability (by 2.8 times) and storage (by ∼30%) and increased the abundance of nifH genes (by ∼14%) and nitrogenase activity (by ∼60%). Nanosized iron (oxyhydr)oxides (ferrihydrite, goethite, and hematite nanoparticles) play a dual role in soil Mo cycling: (i) in concert with microorganisms, they raise Mo bioavailability by catalyzing hydroxyl radical (HO•) production via the Fenton reactions and (ii) they increase Mo retention by association with the nanosized iron (oxyhydr)oxides. In summary, long-term manure fertilization raised the stock and bioavailability of Mo (and probably also of other micronutrients) by increasing iron (oxyhydr)oxide reactivity and intensified asymbiotic N fixation through an increased abundance of nifH genes and nitrogenase activity. This work provides a strategy for increasing biological N fixation in agricultural ecosystems.


Assuntos
Molibdênio , Fixação de Nitrogênio , Disponibilidade Biológica , Ecossistema , Radicais Livres , Ferro , Óxidos , Solo
3.
J Med Genet ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544842

RESUMO

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

4.
J Hematol Oncol ; 14(1): 140, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34493319

RESUMO

BACKGROUND: In the absence of randomized studies directly comparing chimeric antigen receptor T cell therapies, this study used matching-adjusted indirect comparisons (MAIC) to evaluate the comparative efficacy and safety of lisocabtagene maraleucel (liso-cel) versus axicabtagene ciloleucel (axi-cel) in patients with relapsed or refractory large B cell lymphoma (LBCL). METHODS: Primary data sources included individual patient data from the TRANSCEND NHL 001 study (TRANSCEND [NCT02631044]; N = 256 for efficacy set, N = 269 for safety set) for liso-cel and summary-level data from the ZUMA-1 study (NCT02348216; N = 101 for efficacy set, N = 108 for safety set) for axi-cel. Inter-study differences in design, eligibility criteria, baseline characteristics, and outcomes were assessed and aligned to the extent feasible. Clinically relevant prognostic factors were adjusted in a stepwise fashion by ranked order. Since bridging therapy was allowed in TRANSCEND but not ZUMA-1, the initial efficacy and safety analyses included bridging therapy use as a matching factor (TRANSCEND patients who received bridging therapy were removed). Subsequent sensitivity analyses excluded this matching factor. RESULTS: The initial analysis showed similar MAIC-weighted efficacy outcomes between TRANSCEND and ZUMA-1 for overall and complete response rates (odds ratio [95% confidence interval (CI)], 1.40 [0.56-3.49] and 1.21 [0.56-2.64], respectively) and for overall survival and progression-free survival (hazard ratio [95% CI], 0.81 [0.44-1.49] and 0.95 [0.58-1.57], respectively). MAIC-weighted safety outcomes favored liso-cel, with significantly lower odds of all-grade and grade ≥ 3 cytokine release syndrome (odds ratio [95% CI], 0.03 [0.01-0.07] and 0.08 [0.01-0.67], respectively) and study-specific neurological events (0.16 [0.08-0.33] and 0.05 [0.02-0.15], respectively). Efficacy and safety outcomes remained similar in sensitivity analyses, which did not include use of bridging therapy as a matching factor. CONCLUSIONS: After matching and adjusting for clinically relevant prognostic factors, liso-cel demonstrated comparable efficacy and a more favorable safety profile compared with axi-cel in patients with third- or later-line relapsed or refractory LBCL. TRIAL REGISTRATION: NCT02631044 and NCT02348216.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Produtos Biológicos/uso terapêutico , Imunoterapia Adotiva/métodos , Linfoma Difuso de Grandes Células B/terapia , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Produtos Biológicos/efeitos adversos , Feminino , Humanos , Imunoterapia Adotiva/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Resultado do Tratamento
5.
Clin Infect Dis ; 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34406358

RESUMO

BACKGROUND: Post-vaccination myopericarditis is reported after immunization with COVID-19 mRNA-vaccines. The effect of accidental intravenous injection of this vaccine on the heart is unknown. METHODS: We compared the clinical manifestations, histopathological changes, tissue mRNA expression and serum levels of cytokine/chemokine in Balb/c mice at different time points after intravenous(IV) or intramuscular(IM) vaccine injection with normal saline(NS) control. RESULTS: Though significant weight loss and higher serum cytokine/chemokine levels were found in IM group at 1 to 2 days post-injection(dpi), only IV group developed histopathological changes of myopericarditis as evidenced by cardiomyocyte degeneration, apoptosis and necrosis with adjacent inflammatory cell infiltration and calcific deposits on visceral pericardium, while evidence of coronary artery or other cardiac pathologies was absent. SARS-CoV-2 spike antigen expression by immunostaining was occasionally found in infiltrating immune cells of the heart or injection site, in cardiomyocytes and intracardiac vascular endothelial cells, but not skeletal myocytes. The histological changes of myopericarditis after the first IV-priming dose persisted for 2 weeks and were markedly aggravated by a second IM- or IV-booster dose. Cardiac tissue mRNA expression of IL-1ß, IFN-ß, IL-6 and TNF-α increased significantly from 1dpi to 2dpi in IV but not IM group, compatible with presence of myopericarditis in IV group. Ballooning degeneration of hepatocytes was consistently found in IV group. All other organs appeared normal. CONCLUSIONS: This study provided in-vivo evidence that inadvertent intravenous injection of COVID-19 mRNA-vaccines may induce myopericarditis. Brief withdrawal of syringe plunger to exclude blood aspiration may be one possible way to reduce such risk.

6.
Nanomaterials (Basel) ; 11(8)2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34443964

RESUMO

Graphene oxide (GO) is widely used in various fields and has raised concerns regarding its potential environmental fate and effect. However, there are few studies on its influence on coexisting pollutants. In this study, the phototransformation of GO and coexisting sulfamethazine (SMZ) under UV irradiation was investigated, with a focus on the role of reactive oxygen species. The results demonstrated that GO promoted the degradation of SMZ under UV irradiation. The higher the concentration of GO, the higher the degradation rate of SMZ, and the faster the first-order reaction rate. Two main radicals, ∙OH and 1O2, both contributed greatly in terms of regulating the removal of SMZ. Cl-, SO42-, and pH mainly promoted SMZ degradation by increasing the generation of ∙OH, while humic acid inhibited SMZ degradation due to the reduction of ∙OH. Moreover, after UV illumination, the GO suspension changed from light yellow to dark brown with increasing absorbance at a wavelength of 225 nm. Raman spectra revealed that the ID/IG ratio slightly decreased, indicating that some of the functional groups on the surface of GO were removed under low-intensity UV illumination. This study revealed that GO plays important roles in the photochemical transformation of environmental pollutants, which is helpful for understanding the environmental behaviors and risks of nanoparticles in aquatic environments.

7.
Sci Total Environ ; 797: 149180, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34311354

RESUMO

The toxicity of microplastics to marine organisms has attracted much attention; however, studies of their effects on marine microalgae remain limited. Here, the effects of the single and combined toxicity of polystyrene (PS) and triphenyl phosphate (TPhP) on the cell growth, photosynthesis, and oxidative stress of Chaetoceros meülleri were investigated. PS inhibited growth of the algae cells and caused a dose-dependent effect on oxidative stress. The significantly high production of reactive oxygen species (ROS) induced severe cell membrane damage, as confirmed by high fluorescence polarization. However, there was no obvious decrease in chlorophyll a content, and 80 mg/L of PS significantly promoted chlorophyll a synthesis. The TPhP also inhibited cell growth, except at low concentrations (0.2-0.8 mg/L), which stimulated algae growth over 48 h. Moreover, no obvious decrease in chlorophyll a and maximal photochemical efficiency of PSII was found in the TPhP experimental groups except for 3.2 mg/L TPhP, where the rapid light curves showed a significantly reduced photosynthetic capacity of algae. In addition, TPhP caused high ROS levels at 96 h, resulting in cell membrane damage. Using the additive index and independent action methods, the combined toxic effects of PS and TPhP on the algae were evaluated as antagonistic; however, cell membrane damage caused by high ROS levels was still noticeable. This study has shown the potential toxicity of PS and TPhP to marine microalgae, and provided insights into the combined risk assessment of TPhP and microplastics in the marine environment.


Assuntos
Poliestirenos , Poluentes Químicos da Água , Clorofila A , Organofosfatos , Estresse Oxidativo , Fotossíntese , Plásticos , Poliestirenos/toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
8.
Nat Commun ; 12(1): 4193, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234122

RESUMO

Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs. A similar spectrum of somatic aberrations and viral gene expression undermine innate immunity in 79% of cases and adaptive immunity in 47% of cases; mechanisms by which NPC may evade immune surveillance despite its pro-inflammatory phenotype. Additionally, genomic changes impairing TGFBR2 promote oncogenesis and stabilize EBV infection in tumor cells. Fine-mapping of CDKN2A/CDKN2B deletion breakpoints reveals homozygous MTAP deletions in 32-34% of NPCs that confer marked sensitivity to MAT2A inhibition. Our work concludes that NPC is a homogeneously NF-κB-driven and immune-protected, yet potentially druggable, cancer.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/imunologia , Evasão Tumoral/genética , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Carcinogênese/imunologia , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/terapia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Regulação Viral da Expressão Gênica/imunologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/patogenicidade , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Metionina Adenosiltransferase/antagonistas & inibidores , Metionina Adenosiltransferase/metabolismo , Camundongos , NF-kappa B/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/virologia , Nasofaringe/imunologia , Nasofaringe/patologia , Nasofaringe/cirurgia , Nasofaringe/virologia , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Deleção de Sequência , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Evasão Tumoral/efeitos dos fármacos , Sequenciamento Completo do Genoma , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Clin Cancer Res ; 27(15): 4230-4244, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34158359

RESUMO

PURPOSE: Circulating tumor DNA (ctDNA) enables personalized treatment strategies in oncology by providing a noninvasive source of clinical biomarkers. In patients with low ctDNA abundance, tumor-naïve methods are needed to facilitate clinical implementation. Here, using locoregionally confined head and neck squamous cell carcinoma (HNSCC) as an example, we demonstrate tumor-naïve detection of ctDNA by simultaneous profiling of mutations and methylation. EXPERIMENTAL DESIGN: We conducted CAncer Personalized Profiling by deep Sequencing (CAPP-seq) and cell-free Methylated DNA ImmunoPrecipitation and high-throughput sequencing (cfMeDIP-seq) for detection of ctDNA-derived somatic mutations and aberrant methylation, respectively. We analyzed 77 plasma samples from 30 patients with stage I-IVA human papillomavirus-negative HNSCC as well as plasma samples from 20 risk-matched healthy controls. In addition, we analyzed leukocytes from patients and controls. RESULTS: CAPP-seq identified mutations in 20 of 30 patients at frequencies similar to that of The Tumor Genome Atlas (TCGA). Differential methylation analysis of cfMeDIP-seq profiles identified 941 ctDNA-derived hypermethylated regions enriched for CpG islands and HNSCC-specific methylation patterns. Both methods demonstrated an association between ctDNA abundance and shorter fragment lengths. In addition, mutation- and methylation-based ctDNA abundance was highly correlated (r > 0.85). Patients with detectable pretreatment ctDNA by both methods demonstrated significantly worse overall survival (HR = 7.5; P = 0.025) independent of clinical stage, with lack of ctDNA clearance post-treatment strongly correlating with recurrence. We further leveraged cfMeDIP-seq profiles to validate a prognostic signature identified from TCGA samples. CONCLUSIONS: Tumor-naïve detection of ctDNA by multimodal profiling may facilitate biomarker discovery and clinical use in low ctDNA abundance applications.

12.
Adv Ther ; 38(6): 3266-3280, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33970454

RESUMO

Most patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have exhausted their treatment options and are deemed palliative. CD19-directed chimeric antigen receptor (CAR) T-cell therapy has recently been introduced as a new option for these patients. Lisocabtagene maraleucel (liso-cel) is an investigational CAR T-cell therapy that has shown promising activity in this setting. We used an unanchored matching-adjusted indirect comparison (MAIC) methodology to compare liso-cel, using individual patient-level data from the TRANSCEND NHL 001 (TRANSCEND; NCT02631044) trial, to salvage chemotherapy, using summary-level data from the SCHOLAR-1 study, for the treatment of patients with R/R LBCL. Standardized mean differences were used to evaluate imbalances between the TRANSCEND and SCHOLAR-1 studies. MAIC was conducted to determine the relative efficacy of liso-cel vs. salvage chemotherapy with regard to overall survival, complete response rate, and objective response rate. For all efficacy outcomes assessed, comparisons of clinical factors before MAIC showed that five of seven baseline characteristics were similar between the TRANSCEND and SCHOLAR-1 studies; however, age and R/R to last therapy status differed between studies, thus requiring matching and adjusting to ensure the validity of this analysis. The base case analyses demonstrated a significantly lower risk of mortality (hazard ratio, 0.5; 95% confidence interval [CI] 0.4-0.6; p < 0.001) with significantly higher rates of complete response (odds ratio, 12.9; 95% CI 8.0-20.7) and objective response (odds ratio, 7.0; 95% CI 4.6-10.5) for patients treated with liso-cel than patients treated with salvage chemotherapy. MAIC comparisons demonstrated favorable efficacy for liso-cel compared with salvage chemotherapy in the treatment of patients with R/R LBCL.Trial Registration ClinicalTrials.gov identifier: NCT02631044.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Antígenos CD19 , Humanos , Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B/tratamento farmacológico
13.
Nonlinear Dyn ; : 1-17, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34054221

RESUMO

In this paper, a novel two-stage epidemic model with a dynamic control strategy is proposed to describe the spread of Corona Virus Disease 2019 (COVID-19) in China. Combined with local epidemic control policies, an epidemic model with a traceability process is established. We aim to investigate the appropriate control strategies to minimize the control cost and ensure the normal operation of society under the premise of containing the epidemic. This work mainly includes: (i) propose the concept about the first and the second waves of COVID-19, as well as study the case data and regularity of four cities; (ii) derive the existence and stability of the equilibrium, the parameter sensitivity of the model, and the existence of the optimal control strategy; (iii) carry out the numerical simulation associated with the theoretical results and construct a dynamic control strategy and verify its feasibility.

14.
Comput Biol Med ; 133: 104400, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33930766

RESUMO

The field of radiomics is at the forefront of personalized medicine. However, there is concern that high variation in imaging parameters will impact robustness of radiomic features and subsequently the performance of the predictive models built upon them. Therefore, our review aims to evaluate the impact of imaging parameters on the robustness of radiomic features. We also provide insights into the validity and discrepancy of different methodologies applied to investigate the robustness of radiomic features. We selected 47 papers based on our predefined inclusion criteria and grouped these papers by the imaging parameter under investigation: (i) scanner parameters, (ii) acquisition parameters and (iii) reconstruction parameters. Our review highlighted that most of the imaging parameters are disruptive parameters, and shape along with First order statistics were reported as the most robust radiomic features against variation in imaging parameters. This review identified inconsistencies related to the methodology of the reviewed studies such as the metrics used for robustness, the feature extraction techniques, the reporting style, and their outcome inclusion. We hope this review will aid the scientific community in conducting research in a way that is more reproducible and avoids the pitfalls of previous analyses.


Assuntos
Benchmarking , Tomografia Computadorizada por Raios X , Reprodutibilidade dos Testes
15.
BMC Med Ethics ; 22(1): 29, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761938

RESUMO

BACKGROUND: Immense volumes of personal health information (PHI) are required to realize the anticipated benefits of artificial intelligence in clinical medicine. To maintain public trust in medical research, consent policies must evolve to reflect contemporary patient preferences. METHODS: Patients were invited to complete a 27-item survey focusing on: (a) broad versus specific consent; (b) opt-in versus opt-out approaches; (c) comfort level sharing with different recipients; (d) attitudes towards commercialization; and (e) options to track PHI use and study results. RESULTS: 222 participants were included in the analysis; 83% were comfortable sharing PHI with researchers at their own hospital, although younger patients (≤ 49 years) were more uncomfortable than older patients (50 + years; 13% versus 2% uncomfortable, p < 0.05). While 56% of patients preferred broad consent, 38% preferred specific consent; 6% preferred not sharing at all. The majority of patients (63%) preferred to be asked for permission before entry into a contact pool. Again, this trend was more pronounced for younger patients (≤ 49 years: 76%). Approximately half of patients were uncomfortable sharing PHI with commercial enterprises (51% uncomfortable, 27% comfortable, 22% neutral). Most patients preferred to track PHI usage (61%), with the highest proportion once again reported by the youngest patients (≤ 49 years: 71%). A majority of patients also wished to be notified regarding study results (70%). CONCLUSIONS: While most patients were willing to share their PHI with researchers within their own institution, many preferred a transparent and reciprocal consent process. These data also suggest a generational shift, wherein younger patients preferred more specific consent options. Modernizing consent policies to reflect increased autonomy is crucial in fostering sustained public engagement with medical research.


Assuntos
Inteligência Artificial , Registros de Saúde Pessoal , Humanos , Consentimento Livre e Esclarecido , Preferência do Paciente , Confiança
16.
Sci Rep ; 11(1): 4533, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-33633121

RESUMO

Multiple studies have reported a doubling in risk of Coronavirus Disease-2019 (COVID-19) among cancer patients. Here, we examine the potential biological rationale behind this recurrent epidemiological observation. By leveraging large-scale genome-wide transcriptional data of normal and malignant tissues from adults and children, we found evidence of increased expression of SARS-CoV-2 viral entry genes in the cancer state, particularly in respiratory, gastrointestinal, and genitourinary tract tissues, with decreased expression in pediatric vs. adult samples. Additionally, by interrogating the temporal effects of radiotherapy on human peripheral blood mononuclear and mucosal cells, we observed important treatment-related alterations in host innate immunity, specifically type I interferon responses. Overall, cancers enhance expression of critical viral entry genes, and innate viral defenses can be dysregulated transiently during radiation treatments. These factors may contribute to the observed increased susceptibility to SARS-CoV-2 entry and severity of COVID-19 in cancer patients.


Assuntos
COVID-19/complicações , Imunidade Inata , Neoplasias/complicações , SARS-CoV-2/fisiologia , Internalização do Vírus , Adulto , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia , COVID-19/genética , COVID-19/imunologia , Catepsina L/genética , Catepsina L/imunologia , Criança , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/radioterapia , Serina Endopeptidases/genética , Serina Endopeptidases/imunologia , Índice de Gravidade de Doença
17.
Infect Drug Resist ; 14: 467-473, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33603410

RESUMO

Objective: This study aimed to investigate the expression of natural killer (NK) cell subsets in patients with acquired immune deficiency syndrome (AIDS) and deep fungal infections and the significance of such expression. Methods: A total of 829 patients with AIDS, who were treated in People's Hospital of Deyang City our hospital between January 2011 and March 2019, were enrolled in the study. They were divided into two groups: those with human immunodeficiency virus (HIV) and invasive fungal infection (IFI) (HIV + IFI) (n = 390) and those with HIV and no IFI (HIV + non-IFI) (n = 439). Another 200 healthy volunteers were enrolled as the control group. The numbers of NK cell subsets in each group were compared. Results: The level of NK cells, number of NK cells in all lymphocytes, proportions of CD56bright, CD56dim, and CD56dim NK cells in NK cells, and the level of CD56-CD16+ NK cells were significantly lower in the HIV + IFI group than in the HIV + non-IFI group and control group (P < 0.05). Moreover, CD4+ T, CD4+/CD8+, and NK cells were negatively correlated with HIV-RNA expression (P < 0.05). Conclusion: A combination of AIDS and deep fungal infection can change the immune status of a patient. This condition can be diagnosed early through the detection of NK cell expression.

18.
Int J Radiat Oncol Biol Phys ; 110(3): 656-666, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33440225

RESUMO

PURPOSE: To evaluate the 15-year impact of a transdisciplinary research training program for graduate students, postdoctoral fellows, and clinical trainees focused on radiation science, entitled Strategic Training in Transdisciplinary Radiation Science for the 21st Century (STARS21) with a primary objective to build capacity in radiation research. METHODS AND MATERIALS: Alumni (n = 128) and mentors (n = 41) who participated in STARS21 between 2003 and 2018 were sent an anonymized online survey designed to evaluate the program. Twelve alumni and 7 mentors also volunteered to participate in semistructured interviews. The transcribed interviews were coded and analyzed using NVivo12-Pro software. Alumni employment and publications were assessed from program records and by web-based search queries. RESULTS: Alumni are located in 11 countries, and nearly 90% are employed in a research-oriented career and continue to publish in radiation medicine- or cancer-related fields. Of those invited, 46 alumni (36%) and 12 mentors (29%) completed the online survey. Approximately 87% of alumni valued interdisciplinary collaboration, and 80% indicated that STARS21 had encouraged them to pursue such collaborations. Alumni emphasized that STARS21 assisted their career development, and the majority of alumni and mentors would recommend STARS21 to other trainees (4.48 and 4.58, respectively; 5 = strongly agree). The time invested in the program was perceived by mentors as worthwhile for the knowledge and skills gained by trainees (4.67; 5 = strongly agree), and 64% of mentors indicated that these benefits were associated with improved trainee research productivity. From the alumni and mentor perspectives, the valuable skills acquired from STARS21 included scientific communication (85% and 83%, respectively) and networking (83% and 92%, respectively). CONCLUSIONS: STARS21 is an innovative research training program that promotes interdisciplinary collaboration in radiation medicine research, which is valued by alumni and mentor respondents. Alumni can acquire important skill sets for career development, with a large proportion of alumni currently engaged in radiation research around the world.


Assuntos
Pesquisa Biomédica/educação , Pesquisadores/educação , Humanos , Mentores , Avaliação de Programas e Projetos de Saúde , Inquéritos e Questionários
19.
Clin Infect Dis ; 73(3): e719-e734, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-33515458

RESUMO

BACKGROUND: Mass vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing amidst widespread transmission during the coronavirus disease-2019 (COVID-19) pandemic. Disease phenotypes of SARS-CoV-2 exposure occurring around the time of vaccine administration have not been described. METHODS: Two-dose (14 days apart) vaccination regimen with formalin-inactivated whole virion SARS-CoV-2 in golden Syrian hamster model was established. To investigate the disease phenotypes of a 1-dose regimen given 3 days prior (D-3), 1 (D1) or 2 (D2) days after, or on the day (D0) of virus challenge, we monitored the serial clinical severity, tissue histopathology, virus burden, and antibody response of the vaccinated hamsters. RESULTS: The 1-dose vaccinated hamsters had significantly lower clinical disease severity score, body weight loss, lung histology score, nucleocapsid protein expression in lung, infectious virus titers in the lung and nasal turbinate, inflammatory changes in intestines, and a higher serum neutralizing antibody or IgG titer against the spike receptor-binding domain or nucleocapsid protein when compared to unvaccinated controls. These improvements were particularly noticeable in D-3, but also in D0, D1, and even D2 vaccinated hamsters to varying degrees. No increased eosinophilic infiltration was found in the nasal turbinate, lung, and intestine after virus challenge. Significantly higher serum titer of fluorescent foci microneutralization inhibition antibody was detected in D1 and D2 vaccinated hamsters at day 4 post-challenge compared to controls despite undetectable neutralizing antibody titer. CONCLUSIONS: Vaccination just before or soon after exposure to SARS-CoV-2 does not worsen disease phenotypes and may even ameliorate infection.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Cricetinae , Humanos , Mesocricetus , Vacinas de Produtos Inativados
20.
Int J Radiat Oncol Biol Phys ; 109(3): 656-660, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33516435

RESUMO

PURPOSE: The Accelerated Education Program (AEP) at the Princess Margaret Cancer Centre (PM) has been offering continuing medical education courses since 2006. The purpose of this study was to assess learner experiences, perspectives, and outcomes using Kirkpatrick's Four Level Training Evaluation Model (ie, reaction, learning, behavior, results) to ascertain whether it was meeting stated goals. METHODS AND MATERIALS: Past course participants (2010-2018) were invited to participate in a semistructured interview. Interviews were transcribed verbatim; thematic analysis was conducted by a 4-person research team. RESULTS: Seventeen participants including 2 medical physicists, 6 radiation oncologists, and 9 radiation therapists from 6 countries on 4 continents participated in the study. Interviews lasted an average of 25 minutes. Consistently positive outcomes were reported at each level of Kirkpatrick's model. At the reaction level, participants liked the small, interactive case-based design, exposure to renowned faculty and practices from PM and other major centers, and the interprofessional practice (IPP) approach. Suggestions for improvements include enhancing practical content. At the learning level, participants reported gaining new knowledge or skills and new awareness or attitudes. Behavior changes described included sharing learnings with colleagues, implementing changes in practice or techniques, departmental structure, and IPP. Participants described the effects on clinical practice (results) in quality of care, access to care, and academic contribution. Identified barriers to change related to the restricted internal capacity for change and the need for wider staff training. CONCLUSIONS: AEP courses were found to have a positive effect on local practices ranging from confirmation of current practice through to increased access to and quality of advanced radiotherapeutic techniques and care. Our findings confirm that AEP is achieving its goal of "putting innovation to work" and suggest curricular improvements that can enhance these effects.


Assuntos
Educação Médica Continuada , Internacionalidade , Radioterapia (Especialidade)/educação , Atitude do Pessoal de Saúde , Educação Médica Continuada/métodos , Humanos , Aprendizagem , Ontário , Pesquisa Qualitativa , Radio-Oncologistas/educação , Radio-Oncologistas/estatística & dados numéricos
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