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1.
Environ Pollut ; 292(Pt B): 118457, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34742818

RESUMO

A high demand exists in bisphenols (BPs) screening studies for quick, reliable and straightforward analytical methods that generate data faster and simultaneously. Herein, we describe a combination of enzymatic probe sonication (EPS) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for quick extraction and simultaneous quantification of eight important BPs in animal-derived foods. Results obtained demonstrated that the ultrasonic probe power could not only enhance the enzymatic hydrolysis efficiency, but also accelerate the liquid-liquid extraction procedure. Under optimized EPS parameters, one sample could be exhaustively extracted within 120 s, as compared with 12 h needed for the conventional enzymatic extraction which is more suitable for high-throughput analysis. The method was successfully applied to analyze residual BPs in animal-derived foods collected from Beijing, China. Widespread occurrence of BPA, BPS, BPF, BPAF, BPP, and BPB were found, with detection frequencies of 65.2%, 42.4%, 33.7%, 29.4%, 28.3%, and 27.2%, respectively. The highest total concentration levels of BPs (sum of the eight BPs analyzed, ΣBPs) were found in chicken liver (mean 12.2 µg/kg), followed by swine liver (6.37 µg/kg), bovine muscle (3.24 µg/kg), egg (2.03 µg/kg), sheep muscle (2.03 µg/kg), chicken muscle (1.45 µg/kg), swine muscle (1.42 µg/kg), and milk (1.17 µg/kg). The estimated daily intake (EDI) of BPs, based on the mean and 95th percentile concentrations and daily food consumptions, was estimated to be 5.687 ng/kg bw/d and 22.71 ng/kg bw/d, respectively. The human health risk assessment in this work suggests that currently BPs do not pose significant risks to the consumers because the hazard index (HI) was <1.


Assuntos
Sonicação , Espectrometria de Massas em Tandem , Ração Animal , Animais , Compostos Benzidrílicos/análise , Bovinos , Cromatografia Líquida , Leite/química , Ovinos , Suínos
2.
Int Immunopharmacol ; : 108380, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34848154

RESUMO

Discovery of anti-inflammatory drugs that can suppress T lymphocyte activation and proliferation by inhibiting TCR/CD3 and IL-2/IL-2R signaling is still needed in clinic, though rapamycin and other related reagents have made great success. Taraxasterol (TAS) is an active ingredient of dandelion, an anti-inflammatory medicinal herb with low in vivo toxicity that has long been used in China. Yet the action mechanism of TAS on lymphocytes remains elusive. The anti-inflammatory effects of TAS were evaluated in C57BL/6 mouse primary lymphocytes stimulated with concanavalin A (Con A) in vitro and in mouse model of Con A-induced acute hepatitis in vivo. Our results showed that TAS significantly suppressed Con A-induced acute hepatitis in a mouse model, reducing the hepatic necrosis areas, the release of aminotransferases, and the production of IL-2 and other inflammatory cytokines. Supporting this, in vitro study also showed that TAS reduced the production of IL-2 and the expression of IL-2 receptor subunit α (CD25) upon the stimulation of Con A, which was likely mediated by suppressing NF-κB activation. The downstream pathways of IL-2/IL-2R signaling, including the activation of PI3K/PDK1/mTOR, STAT3 and STAT5, were also suppressed by TAS. Consistently, Con A-induced T cell proliferation was also inhibited by TAS in vitro. Our data indicate that TAS can suppress both T lymphocyte activation and cell proliferation by down-regulating IL-2 expression and its signaling pathway thereby ameliorating Con A-induced acute hepatitis, highlighting TAS as a potential drug candidate for treating inflammatory diseases including autoimmune hepatitis.

3.
Front Plant Sci ; 12: 762889, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745194

RESUMO

Melon (Cucumis melo) is one of the top 10 fruits in the world, and its production often suffers due to soil-borne diseases. Grafting is an effective way to solve this problem. However, graft incompatibility between scion and rootstock limits the application of melon grafting. In this study, the melon was grafted onto eight Cucurbitaceae species (cucumber, pumpkin, melon, luffa, wax gourd, bottle gourd, bitter gourd, and watermelon), and graft compatibility evaluation and anatomical observation were conducted. Taking melon homo-grafted plants as control, melon grafted onto cucumber and pumpkin rootstocks was compatible, while melon grafted onto luffa, wax gourd, bottle gourd, bitter gourd, and watermelon rootstocks was incompatible based on the scion dry weight on day 42 after grafting. Meanwhile, we found that starch-iodine staining of scion stem base is an index to predict graft compatibility earlier, on day 14 after grafting. Further, microsection observations showed that there was more cell proliferation at graft junction of melon hetero-grafted combinations; vascular reconnection occurred in all graft combinations. However, excess callose deposited at graft junction resulted in the blockage of photosynthate transport, thus, leading to starch accumulation in scion stem base, and finally graft incompatibility. In addition, undegraded necrotic layer fragments were observed at graft junctions of melon grafted onto incompatible bitter gourd and watermelon rootstocks. The above results provide clues for the selection and breeding of compatible Cucurbitaceae rootstocks of melon and demonstrate that starch accumulation in scion base and callose deposition at graft junction is associated with melon graft compatibility.

4.
Toxicol Res (Camb) ; 10(4): 696-705, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34745557

RESUMO

This study aimed to clarify the mechanism of propofol on proliferation and apoptosis of colorectal cancer (CRC) cell. SW620 and HCT15 cells were exposed to different concentrations of propofol, the proliferation and apoptotic rate, were measured by MTT, colony formation and flow cytometry assays, respectively. The expressions of miR-1-3p and insulin-like growth factors 1 (IGF1) were examined by real-time polymerase chain reaction (RT-qPCR). Western bolt was employed to quantify the protein levels of IGF1 and apoptotic proteins. The molecular interaction between miR-1-3p and IGF1 was validated using dual-luciferase reporter assay. A xenograft tumor model was established to further assess the effects of propofol on CRC in vivo. Propofol dramatically decreased the proliferation and elevated apoptotic rate of CRC cells. RT-qPCR assay demonstrated that miR-1-3p was downregulated in CRC cells, and could be strikingly increased by propofol. Importantly, miR-1-3p inhibited IGF-1 expression through interacting with its 3'-UTR region, thus inactivating AKT/mTOR signals. Gain or loss of functional study revealed that miR-1-3p downregulation remarkedly diminished the anti-tumor roles of propofol by directly inhibiting IGF1. In vivo study showed that propofol inhibited tumor growth by regulating miR-1-3p/IGF1 axis. Our data eventually elucidated that propofol suppressed CRC progression by promoting miR-1-3p which targeted IGF1. These results might provide a scientific basis for the application of propofol on the clinical surgery and the prognosis of patients with CRC.

5.
J Transl Med ; 19(1): 463, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772407

RESUMO

BACKGROUND: Intestinal ischemia/reperfusion (I/R) injury commonly occurs during perioperative periods, resulting in high morbidity and mortality on a global scale. Dexmedetomidine (Dex) is a selective α2-agonist that is frequently applied during perioperative periods for its analgesia effect; however, its ability to provide protection against intestinal I/R injury and underlying molecular mechanisms remain unclear. METHODS: To fill this gap, the protection of Dex against I/R injury was examined in a rat model of intestinal I/R injury and in an inflammation cell model, which was induced by tumor necrosis factor-alpha (TNF-α) plus interferon-gamma (IFN-γ) stimulation. RESULTS: Our data demonstrated that Dex had protective effects against intestinal I/R injury in rats. Dex was also found to promote mitophagy and inhibit apoptosis of enteric glial cells (EGCs) in the inflammation cell model. PINK1 downregulated p53 expression by promoting the phosphorylation of HDAC3. Further studies revealed that Dex provided protection against experimentally induced intestinal I/R injury in rats, while enhancing mitophagy, and suppressing apoptosis of EGCs through SIRT3-mediated PINK1/HDAC3/p53 pathway in the inflammation cell model. CONCLUSION: Hence, these findings provide evidence supporting the protective effect of Dex against intestinal I/R injury and its underlying mechanism involving the SIRT3/PINK1/HDAC3/p53 axis.

6.
J Control Release ; 341: 215-226, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34822908

RESUMO

Although the individual role of ligand modification or rigidity modulation on oral administration of nanoparticle (NP) has been investigated, how they mutually affect each other remains to be elucidated. Here, we fabricated different rigidity NP with or without surface decoration of FcBP, a neonatal Fc receptor domain-binding peptide. In vitro studies showed that, without FcBP modification, stiff NP had higher transcytosis efficiency across the epithelium than softer NP, due to the different endocytosis mechanisms, intracellular trafficking routes, and exocytosis rate. Notably, after FcBP modification, such difference was narrowed, in a manner that was more favorable for softer NP to "catch up" with stiff NP, suggesting ligand modification was more conducive to exert transcytosis-promoting efficacy on softer NP. In vivo experiments demonstrated that, for ligand-free NP, high rigidity was required for efficient oral absorption and liver distribution. Further FcBP modification decreased that "rigidity threshold", and expanded the feasible rigidity range from stiff NP to softer NP. Upon oral administration, FcBP-modified dexamethasone-loaded softer NP achieved a therapeutic efficacy comparable with stiff NP on alleviating liver fibrosis. Collectively, our study highlighted the necessity of coordinating ligand modification and rigidity modulation for oral drug delivery.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34817983

RESUMO

The protein corona on nanoparticles (NPs) is a critical problem that often screens the targeting molecules and becomes one of the key reasons for the lack of practical application in nanotherapy. It is critical to fully understand the mechanism of the nanoparticle-biological interactions to design the nanoparticle-based therapeutic agents. Some types of proteins can be precoated on the nanoparticles to avoid unwanted protein attachment; however, the ultralow level of protein corona is hard to achieve, and the relationship of the antifouling property of the precoated protein nanoparticles with protein conformation and protein-nanoparticle interaction energy has never been investigated. In this work, we provided the quantitative protein corona composition analysis on different precoated protein nanoparticles, and on the basis of the molecular simulation process, we found their antifouling property strongly depended on the interaction energy of the precoated protein-serum protein pair and the number of hydrogen bonds formed between them. Furthermore, it also depended on the nanoparticle-serum protein pair interaction energy and the protein conformation on the nanoparticle. The casein coated nanoparticle with the antifouling property was determined, and after aptamer conjugation and drug loading, they exhibited superior targeting and internalization behavior for photodynamic and photothermal therapy in vitro and in vivo. Our work adds to the understanding of the protein corona behavior of precoated protein nanoparticles, and the determined antifouling NP can potentially be used as a highly efficient nanodrug carrier.

8.
Genet Mol Biol ; 44(4): e20210095, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34826835

RESUMO

Blumea balsamifera (L.) DC., a medicinal plant with high economic value in the Asteraceae family, is widely distributed in China and Southeast Asia. However, studies on the population structure or phylogenetic relationships with other related species are rare owing to the lack of genome information. In this study, through high-throughput sequencing, we found that the chloroplast genome of B. balsamifera was 151,170 bp in length, with a pair of inverted repeat regions (IRa and IRb) comprising 24,982 bp, a large single-copy (LSC) region comprising 82,740 bp, and a small single-copy (SSC) region comprising 18,466 bp. A total of 130 genes were identified in the chloroplast genome of B. balsamifera, including 85 protein-coding, 37 transfer RNA, and 8 ribosomal RNA genes; furthermore, sequence analysis identified 53 simple sequence repeats. Whole chloroplast genome comparison indicated that the inverted regions (IR) were more conserved than large single-copy and SSC regions. Phylogenetic analysis showed that B. balsamifera is closely related to Pluchea indica. Conclusively, the chloroplast genome of B. balsamifera was helpful for species identification and analysis of the genetic diversity and evolution in the genus Blumea and family Asteraceae.

9.
BMC Med Inform Decis Mak ; 21(Suppl 1): 308, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34736437

RESUMO

BACKGROUND: Disease-drug associations provide essential information for drug discovery and disease treatment. Many disease-drug associations remain unobserved or unknown, and trials to confirm these associations are time-consuming and expensive. To better understand and explore these valuable associations, it would be useful to develop computational methods for predicting unobserved disease-drug associations. With the advent of various datasets describing diseases and drugs, it has become more feasible to build a model describing the potential correlation between disease and drugs. RESULTS: In this work, we propose a new prediction method, called LMFDA, which works in several stages. First, it studies the drug chemical structure, disease MeSH descriptors, disease-related phenotypic terms, and drug-drug interactions. On this basis, similarity networks of different sources are constructed to enrich the representation of drugs and diseases. Based on the fused disease similarity network and drug similarity network, LMFDA calculated the association score of each pair of diseases and drugs in the database. This method achieves good performance on Fdataset and Cdataset, AUROCs were 91.6% and 92.1% respectively, higher than many of the existing computational models. CONCLUSIONS: The novelty of LMFDA lies in the introduction of multimodal fusion using low-rank tensors to fuse multiple similar networks and combine matrix complement technology to predict potential association. We have demonstrated that LMFDA can display excellent network integration ability for accurate disease-drug association inferring and achieve substantial improvement over the advanced approach. Overall, experimental results on two real-world networks dataset demonstrate that LMFDA able to delivers an excellent detecting performance. Results also suggest that perfecting similar networks with as much domain knowledge as possible is a promising direction for drug repositioning.


Assuntos
Biologia Computacional , Preparações Farmacêuticas , Algoritmos , Bases de Dados Factuais , Descoberta de Drogas , Reposicionamento de Medicamentos
10.
Pediatr Cardiol ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34779880

RESUMO

The relationship between center-specific variation in indication for pediatric heart transplantation and short-term outcomes after heart transplantation is not well described. We used merged patient- and hospital-level data from the United Network for Organ Sharing and the Pediatric Health Information Systems to analyze outcomes according to transplant indication for a cohort of children (≤ 21 years old) who underwent heart transplantation between 2004 and 2015. Outcomes included 30-day mortality, transplant hospital admission mortality, and hospital length of stay, with multivariable adjustment performed according to patient and center characteristics. The merged cohort reflected 2169 heart transplants at 20 U.S. centers. The median number of transplants annually at each center was 11.6, but ranged from 3.5 to 22.6 transplants/year. Congenital heart disease was the indication in the plurality of cases (49.2%), with cardiomyopathy (46%) and myocarditis (4.8%) accounting for the remainder. There was significant center-to-center variability in congenital heart disease as the principal indication, ranging from 15% to 66% (P < 0.0001). After adjustment, neither center volume nor proportion of indications for transplantation were associated with 30-day or transplant hospital admission mortality. In this large, merged pediatric cohort, variation was observed at center level in annual transplant volume and prevalence of indications for heart transplantation. Despite this variability, center volume and proportion of indications represented at a given center did not appear to impact short-term outcomes.

11.
Nanomaterials (Basel) ; 11(11)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34835542

RESUMO

Metal-supported catalyst with high activity and relatively simple preparation method is given priority to industrial production. In this work, this study reported an easily accessible synthesis strategy to prepare Mott-Schottky-type N-doped carbon encapsulated metallic Co (Co@Np+gC) catalyst by high-temperature pyrolysis method in which carbon nitride (g-C3N4) and dopamine were used as support and nitrogen source. The prepared Co@Np+gC presented a Mott-Schottky effect; that is, a strong electronic interaction of metallic Co and N-doped carbon shell was constructed to lead to the generation of Mott-Schottky contact. The metallic Co, due to high work function as compared to that of N-doped carbon, transferred electrons to the N-doped outer shell, forming a new contact interface. In this interface area, the positive and negative charges were redistributed, and the catalytic hydrogenation mainly occurred in the area of active charges. The Co@Np+gC catalyst showed excellent catalytic activity in the hydrogenation of phenylacetylene to styrene, and the selectivity of styrene reached 82.4%, much higher than those of reference catalysts. The reason for the promoted semi-hydrogenation of phenylacetylene was attributed to the electron transfer of metallic Co, as it was caused by N doping on carbon.

12.
Heart Rhythm ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34843967

RESUMO

BACKGROUND: Mutations in cardiac sodium channel Nav1.5 cause Brugada syndrome (BrS). MOG1 is a chaperon that binds to Nav1.5, facilitates Nav1.5 trafficking to cell surface, and enhances amplitude of sodium current INa. OBJECTIVE: To identify structural elements involved in MOG1-Nav1.5 interaction and their relevance to the pathogenesis of BrS. METHODS: Systematic analyses of large deletions, microdeletions and point mutations. Glutathione S-transferases pull-down, co-immunoprecipitation, cell surface protein quantification and patch-clamping of INa. RESULTS: Large deletion analysis defined the MOG1-Nav1.5 interaction domain to amino acids S476-H585 of Nav1.5 Loop I connecting transmembrane domains I and II. Microdeletion and point mutation analyses further defined the domain to F530T531F532R533R534R535. Mutations F530A, F532A, R533A and R534A, but not T531A and R535A, significantly reduced MOG1-Nav1.5 interaction, and eliminated MOG1-enhanced INa. Mutagenesis analysis identified D24, E36, D44, E53, and E101A of MOG1 as critical residues for interaction with Nav1.5 Loop I. We then characterized three mutations at the MOG1-Nav1.5 interaction domain, p.F530V, p.F532C and p.R535Q reported from patients with LQTS and BrS. We found that p.F532C reduced MOG1-Nav1.5 interaction, and eliminated MOG1 function on INa; p.R535Q is also a loss-of-function mutation that reduces INa amplitude in a MOG1-independent manner, whereas p.F530V is benign as it does not have apparent effect on MOG1 and INa. CONCLUSIONS: Our findings define the MOG1-Nav1.5 interaction domain to a 5-amino-acid motif of F530T531F532R533R534 in Loop I. Mutation p.F532C associated with BrS abolishes Nav1.5 interaction with MOG1 and reduces MOG1-enhanced INa density, thereby uncovering a novel molecular mechanism for the pathogenesis of BrS.

13.
ACS Nano ; 15(10): 16589-16596, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34606233

RESUMO

Microscopically visualizing the evolution of electronic structures at the interface between two electron-correlated domains shows fundamental importance in both material science and physics. Here, we report scanning tunneling microscopy and spectroscopy studies of the interfacial electronic structures evolution in a phase-engineered monolayer NbSe2 heterostructure. The H-NbSe2 metallic state penetrates the Mott insulating T-NbSe2 at the H/T phase interface, with a prominent 2D charge density wave (CDW) proximity effect. Moreover, an insulating Mott gap collapse with the disappearance of the upper Hubbard band is detected at the electronic phase transition region. Theoretical calculations reveal that such insulating Mott gap collapse can be attributed to the electron doping effect induced by the interface. Our findings promote a microscopical understanding of the interactions between different electron-correlated systems and provide an effective method for controlling the Mott insulating states with phase engineering.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34672476

RESUMO

BACKGROUND: Port-wine stains occur in 0.3-0.5% newborns, mainly on the face and neck. Pulsed dye laser is recognized as the gold standard treatment; nevertheless, it is associated with a low cure rate and a high recurrence rate. AIMS: This study aims to evaluate the efficacy of hemoporfin photodynamic therapy for pulsed dye laser-resistant port-wine stains in children. METHODS: We studied 107 children who received hemoporfin photodynamic therapy for port-wine stains on the face and neck that were resistant to pulsed dye laser. After intravenous injection of 5 mg/kg hemoporfin, the local lesion was irradiated with 532 nm LED green light for 20 min with a power density of 80-100 mW/cm2. A total of 65 patients were given a second treatment after eight weeks. The efficacy and therapeutic responses were recorded at four days and eight weeks after each treatment. RESULTS: The efficacy was positively correlated with the number of treatments received; two treatment sessions yielded significantly better results compared to a single treatment with a response rate of 96.9%, a significant response rate of 50.8% and a cure rate of 21.5%, respectively (P < 0.001). After two treatment sessions, the efficacy was negatively correlated with age (P = 0.04). The efficacy for port-wine stains located on the lateral part was better than that of the central face (P = 0.04). The efficacy for the pink type was better than that for the red and purple types (P = 0.03). No allergic or systematic adverse reactions were reported. LIMITATIONS: No objective measurement data were available. CONCLUSION: Hemoporfin photodynamic therapy is effective and safe for pulsed dye laser-resistant facial port-wine stains in children.

15.
Bioinorg Chem Appl ; 2021: 4763944, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34691164

RESUMO

Development of multiple agents has a significant impact on the cancer diagnosis and therapy. Several fluorescent dyes including near-infrared (NIR) fluorescent agents have been already well studied in the field of photodynamic therapy (PDT). In the present study, we reported a novel fluorescent dye could obviously inhibit cancer cell proliferation with slight toxic effects on the biological organism. Furthermore, it displayed selective staining on cancer cells, particularly on cancer stem cells (CSCs), rather than normal cells. Mechanically, this dye preferred to invading mitochondria of cancer cells and inducing overwhelming reactive oxygen species (ROS) production. The in vivo experiments further demonstrated that this dye could image cancer cells and even CSCs in a short-time intratumor injection manner using a zebrafish model and subsequently inhibit cancer cell proliferation after a relatively long-time drug exposure. Taken together, the future development of this agent will promise to make an essential contribution to the cancer diagnosis and therapeutics.

16.
Build Simul ; : 1-18, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34659649

RESUMO

This study conducted the numerical models validated by wind-tunnel experiments to investigate the issues of Re-independence of indoor airflow and pollutant dispersion within an isolated building. The window Reynolds number (Re w ) was specified to characterize the indoor flow and dispersion. The indicators of RRC (ratio of relative change) or DR (K_DR) (difference ratio of dimensionless concentration) ≤ 5% were applied to quantitatively determine the critical Re w for indoor flow and turbulent diffusion. The results show that the critical Re (Re crit) value is position-dependent, and Re crit at the most unfavorable position should be suggested as the optimal value within the whole areas of interest. Thus Re H,crit = 27,000 is recommended for the outdoor flows; while Re w,crit = 15,000 is determined for the indoor flows due to the lower part below the window showing the most unfavorable. The suggested Re w,crit (=15,000) for indoor airflow and cross ventilation is independence of the window size. Moreover, taking K_DR ≤ 5% as the indicator, the suggested Re w,crit for ensuring indoor pollutant diffusion enter the Re-independence regime should also be 15,000, indicating that indoor passive diffusion is completely determined by the flow structures. The contours of dimensionless velocity (U/U 0) and concentration (K) against the increasing Re w further confirmed this critical value. This study further reveals the Re-independence issues for indoor flow and dispersion to ensure the reliability of the data obtained by reduced-scale numerical or wind-tunnel models.

17.
Insects ; 12(10)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34680687

RESUMO

Whole mitogenomes are a useful data source for a wide variety of research goals due to the vastly cheaper sequencing cost and the far less demanding high-quality templates. The mitogenome has demonstrated great potential in resolving phylogenetic questions in Orthoptera at different taxonomic scales as well as exploring patterns of molecular and morphological character evolutions. In this study, the complete mitogenome of Alulacrisshilinensis (Zheng, 1977) was sequenced using next-generation sequencing, the characteristics of the mitogenome are presented briefly, and the phylogeny of the Melanoplinae and Catantopinae was reconstructed using a selected dataset of mitogenome sequences under maximum likelihood and Bayesian inference frameworks. The results show that the genus was consistently assigned to the subfamily Melanoplinae rather than Catantopinae in all phylogenetic trees deduced from different datasets under different frameworks, and this finding is entirely consistent with its morphological characters. Therefore, it is more appropriate to place the genus Alulacris in Melanoplinae rather than in Catantopinae.

18.
Cancer ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34644414

RESUMO

BACKGROUND: The objective of this study was to examine long-term outcomes among children newly diagnosed with cancer who were treated in dexrazoxane-containing clinical trials. METHODS: P9404 (acute lymphoblastic leukemia/lymphoma [ALL]), P9425 and P9426 (Hodgkin lymphoma), P9754 (osteosarcoma), and Dana-Farber Cancer Institute 95-01 (ALL) enrolled 1308 patients between 1996 and 2001: 1066 were randomized (1:1) to doxorubicin with or without dexrazoxane, and 242 (from P9754) were nonrandomly assigned to receive dexrazoxane. Trial data were linked with the National Death Index, the Organ Procurement and Transplantation Network, the Pediatric Health Information System (PHIS), and Medicaid. Osteosarcoma survivors from the Childhood Cancer Survivor Study (CCSS; n = 495; no dexrazoxane) served as comparators in subanalyses. Follow-up events were assessed with cumulative incidence, Cox regression, and Fine-Gray methods. RESULTS: In randomized trials (cumulative prescribed doxorubicin dose, 100-360 mg/m2 ; median follow-up, 18.6 years), dexrazoxane was not associated with relapse (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63-1.13), second cancers (HR, 1.19; 95% CI, 0.62-2.30), all-cause mortality (HR, 1.07; 95% CI, 0.78-1.47), or cardiovascular mortality (HR, 1.45; 95% CI, 0.41-5.16). Among P9754 patients (all exposed to dexrazoxane; cumulative doxorubicin, 450-600 mg/m2 ; median follow-up, 16.6-18.4 years), no cardiovascular deaths or heart transplantation occurred. The 20-year heart transplantation rate among CCSS osteosarcoma survivors (mean doxorubicin, 377 ± 145 mg/m2 ) was 1.6% (vs 0% in P9754; P = .13). Among randomized patients, serious cardiovascular outcomes (cardiomyopathy, ischemic heart disease, and stroke) ascertained by PHIS/Medicaid occurred less commonly with dexrazoxane (5.6%) than without it (17.6%; P = .02), although cardiomyopathy rates alone did not differ (4.4% vs 8.1%; P = .35). CONCLUSIONS: Dexrazoxane did not appear to adversely affect long-term mortality, event-free survival, or second cancer risk.

19.
J Affect Disord ; 295: 839-845, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34706454

RESUMO

BACKGROUND: We investigated factors associated with vulnerability to the psychological impact of celebrity suicide news reporting after the suicide of an emerging Taiwanese novelist, Ms Yi-Han Lin. METHODS: We conducted a cross-sectional online survey. Participants completed a questionnaire which asked whether they were affected by the media coverage of Lin's suicide and whether they would seek help if affected. Logistic regression was used to identify factors associated with being affected by the celebrity suicide media reporting and, among those affected, factors associated with feeling suicidal or not seeking help. RESULTS: A total of 1258 respondents (81% females) completed the survey. Affected individuals (n=907; 70%) were more likely to be females, younger (age < 40 years), have past psychiatric treatment, and show increased interest in the incident (e.g., spending more time on reading the celebrity suicide news) than non-affected individuals. Among those affected, negative views of the media reporting impact, pessimistic attitude toward both depression treatment and suicide prevention, and having a history of past psychiatric treatment were associated with feeling suicidal, while low education attainment, increased interest in the celebrity suicide, and permissive attitude toward inappropriate media reporting were additionally associated with not seeking help. LIMITATIONS: Selection bias of participants through internet-based surveying should be considered. CONCLUSION: Individuals affected by the media coverage of celebrity suicide showed similar demographic and mental health characteristics as those of the deceased celebrity. Poor mental health and suicide prevention literacy may increase the risk of psychological impact and not seeking help. Future interventions could target at enhancing mental health literacy and help seeking intention in vulnerable individuals.


Assuntos
Pessoas Famosas , Suicídio , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Ideação Suicida , Inquéritos e Questionários
20.
JAMA Netw Open ; 4(10): e2128385, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34709389

RESUMO

Importance: Pediatric acute myeloid leukemia (AML) requires multiple courses of intensive chemotherapy that result in neutropenia, with significant risk for infectious complications. Supportive care guidelines recommend hospitalization until neutrophil recovery. However, there are little data to support inpatient over outpatient management. Objective: To evaluate outpatient vs inpatient neutropenia management for pediatric AML. Design, Setting, and Participants: This cohort study used qualitative and quantitative methods to compare medical outcomes, patient health-related quality of life (HRQOL), and patient and family perceptions between outpatient and inpatient neutropenia management. The study included patients from 17 US pediatric hospitals with frontline chemotherapy start dates ranging from January 2011 to July 2019, although the specific date ranges differed for the individual analyses by design and relative timing. Data were analyzed from August 2019 to February 2020. Exposures: Discharge to outpatient vs inpatient neutropenia management. Main Outcomes and Measures: The primary outcomes of interest were course-specific bacteremia incidence, times to next course, and patient HRQOL. Course-specific mortality was a secondary medical outcome. Results: Primary quantitative analyses included 554 patients (272 [49.1%] girls and 282 [50.9%] boys; mean [SD] age, 8.2 [6.1] years). Bacteremia incidence was not significantly different during outpatient vs inpatient management (67 courses [23.8%] vs 265 courses [29.0%]; adjusted rate ratio, 0.73; 95% CI, 0.56 to 1.06; P = .08). Outpatient management was not associated with delays to the next course compared with inpatient management (mean [SD] 30.7 [12.2] days vs 32.8 [9.7] days; adjusted mean difference, -2.2; 95% CI, -4.1 to -0.2, P = .03). Mortality during intensification II was higher for patients who received outpatient management compared with those who received inpatient management (3 patients [5.4%] vs 1 patient [0.5%]; P = .03), but comparable with inpatient management at other courses (eg, 0 patients vs 5 patients [1.3%] during induction I; P = .59). Among 97 patients evaluated for HRQOL, outcomes did not differ between outpatient and inpatient management (mean [SD] Pediatric Quality of Life Inventory total score, 70.1 [18.9] vs 68.7 [19.4]; adjusted mean difference, -2.8; 95% CI, -11.2 to 5.6). A total of 86 respondents (20 [23.3%] in outpatient management, 66 [76.7%] in inpatient management) completed qualitative interviews. Independent of management strategy received, 74 respondents (86.0%) expressed satisfaction with their experience. Concerns for hospital-associated infections among caregivers (6 of 7 caregiver respondents [85.7%] who were dissatisfied with inpatient management) and family separation (2 of 2 patient respondents [100%] who were dissatisfied with inpatient management) drove dissatisfaction with inpatient management. Stress of caring for a neutropenic child at home (3 of 3 respondents [100%] who were dissatisfied with outpatient management) drove dissatisfaction with outpatient management. Conclusions and Relevance: This cohort study found that outpatient neutropenia management was not associated with higher bacteremia incidence, treatment delays, or worse HRQOL compared with inpatient neutropenia management among pediatric patients with AML. While outpatient management may be safe for many patients, course-specific mortality differences suggest that outpatient management in intensification II should be approached with caution. Patient and family experiences varied, suggesting that outpatient management may be preferred by some but may not be feasible for all families. Further studies to refine and standardize safe outpatient management practices are warranted.

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