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2.
Res Q Exerc Sport ; 94(2): 322-330, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35348439

RESUMO

Purpose: The purpose of this study was to compare the impact of interventions aimed at improving teacher's content knowledge on students' MVPA, on-task behavior, and skill performance. Differences between treatment and comparison groups were further examined by skill level and gender. Method: We conducted a retroactive analysis of teacher and student data from two randomly controlled trials and one well-controlled quasi-experimental trial measuring MVPA, student performance in badminton, and on-task behavior in lessons. We used descriptive and ANOVA analyses to determine our results. Results: The data show statistically significant effects for student performance and MVPA, and statistically significant effects for on-task performance between groups. Effect sizes for student performance exceed 1SD. MVPA for two of the three studies exceeded the 50% of the lesson criterion. Data are reported for high, average and low skilled students for each variable. Conclusions: This is the first study to examine three important outcomes of physical education, namely skill performance, MVPA, and on-task behavior in one investigation. Our results show that multiple objectives in physical education can be achieved. A strength of the study is that we did not sample any of our variables. The data represent a complete picture of every trial, and continuous interval recording for MVPA and on-task variables occurring in each lesson.


Assuntos
Exercício Físico , Instituições Acadêmicas , Humanos , Atividade Motora , Estudantes , Educação Física e Treinamento
3.
Healthcare (Basel) ; 10(11)2022 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-36421598

RESUMO

The coronavirus (COVID-19) pandemic has emphasized a need to assess the cause of vaccine hesitancy. This study verified the reliability and validity of the Korean versions of the COVID-19 vaccine hesitancy scale and vaccine conspiracy belief scale and the correlation between them. The COVID-19 vaccine hesitancy scale, Korean COVID-19 vaccine hesitancy scale, vaccine conspiracy beliefs scale, and self-efficacy scale were the study tools. Following translation into Korean, back translation into English, content validity verification, and preliminary survey, valid samples were obtained from 400 adults aged >20 years. Exploratory factor analysis revealed that "belief" and "lack of trust" accounted for 62.4% of the total variance. The model fit index of the vaccine conspiracy beliefs scale revealed that all values were in a good range. The Korean version of the COVID-19 vaccine hesitancy scale showed a positive correlation with vaccine conspiracy beliefs (r = 0.74, p < 0.001) and a significant negative correlation with self-efficacy (r = −0.17, p < 0.001). The validity and reliability of the COVID-19 vaccine hesitancy scale and vaccine conspiracy beliefs scale were verified. The Korean versions of the two scales can contribute to programs that measure and mediate various factors influencing vaccination during the COVID-19 pandemic.

4.
Eur J Nucl Med Mol Imaging ; 50(1): 14-26, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36028577

RESUMO

PURPOSE: Previous SPECT and PET semi-quantitative in vivo imaging studies in monkeys have demonstrated specific uptake of radiolabeled rhesus recombinant anti-CD4 monoclonal antibody fragment CD4R1-F(ab΄)2 in the spleen and clusters of lymph nodes (LNs) but yielded conflicting results of imaging the gut CD4 + T-cell pool. Here, using PET dynamic imaging with kinetic analysis, we performed a fully quantitative CD4 imaging in rhesus macaques. METHODS: The biodistributions of [89Zr]Zr-CD4R1-F(ab΄)2 and/or of [89Zr]Zr-ibalizumab were performed with static PET scans up to 144 h (6 days) post-injection in 18 rhesus macaques with peripheral blood CD4 + T cells/µl ranging from ~ 20 to 2400. Fully quantitative analysis with a 4-h dynamic scan, arterial sampling, metabolite evaluation, and model fitting was performed in three immunocompetent monkeys to estimate the binding potential of CD4 receptors in the LNs, spleen, and gut. RESULTS: The biodistributions of [89Zr]Zr-CD4R1-F(ab΄)2 and [89Zr]Zr-ibalizumab were similar in lymphoid tissues with a clear delineation of the CD4 pool in the LNs and spleen and a significant difference in lymphoid tissue uptake between immunocompetent and immunocompromised macaques. Consistent with our previous SPECT imaging of [99mTc]Tc-CD4R1-F(ab΄)2, the [89Zr]Zr-CD4R1-F(ab΄)2 and [89Zr]Zr-Ibalizumab uptakes in the gut were low and not different between uninfected and SIV-infected CD4-depleted monkeys. Ex vivo studies of large and small intestines confirmed the in vivo images. CONCLUSION: The majority of specific binding to CD4 + tissue was localized to LNs and spleen with minimal uptake in the gut. Binding potential derived from fully quantitative studies revealed that the contribution of the gut is lower than the spleen's contribution to the total body CD4 pool.


Assuntos
Tomografia por Emissão de Pósitrons , Zircônio , Animais , Macaca mulatta , Cinética , Tomografia por Emissão de Pósitrons/métodos
5.
AAPS J ; 24(4): 79, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35790574

RESUMO

On February 24, 2021, the U.S. Food and Drug Administration (FDA) approved an efficacy supplement for HUMIRA® (adalimumab) injection to expand the indication of treatment of moderately to severely active ulcerative colitis (UC) to include pediatric patients 5 years of age and older. The effectiveness in pediatric patients with moderately to severely active UC was studied in a multicenter, randomized, double-blind trial (Study PUC-I, NCT02065557) in 93 pediatric patients 5 to 17 years of age. Adalimumab has been widely studied in multiple indications in adult and pediatric populations with a well-established safety profile; no apparent exposure-safety relationship has been identified in various pediatric populations treated with adalimumab across multiple indications. The approved dosing regimen in pediatric patients with UC differs from the regimen studied in the clinical trial and was determined based on a model-informed exposure bridging strategy, incorporating both efficacy and safety considerations. Specifically, the differences included switches from body weight-based (mg/kg) dosing regimens used in the pediatric trial to body weight-tiered, fixed-dose regimens, changes in dosing schedule, and the addition of an option of a less frequent dosing regimen for maintenance that was not studied in the clinical trial. This article provides a case example of successful model-informed drug development (MIDD), where modeling and simulation were utilized in combination with observed data from a clinical trial of limited size and scope to ultimately support the adalimumab approval in pediatric patients with UC.


Assuntos
Adalimumab , Colite Ulcerativa , Adalimumab/uso terapêutico , Adolescente , Peso Corporal , Criança , Pré-Escolar , Colite Ulcerativa/tratamento farmacológico , Desenvolvimento de Medicamentos , Humanos , Estados Unidos , United States Food and Drug Administration
6.
PLoS One ; 17(5): e0266409, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35580109

RESUMO

Transforming growth factor-ß (TGF-ß) is an important inducer of the epithelial-to-mesenchymal transition (EMT) in various cancers. Our previous study demonstrated that prohaptoglobin (proHp) stimulates Smad1/5 activation via ALK1, a TGF-ß type I receptor, in endothelial cells, suggesting that proHp plays a role in TGF-ß signaling. However, the function of proHp in cellular events downstream of Smads remains unclear. The current study investigated the effects of proHp on TGF-ß-mediated Smad-dependent EMT induction and cell invasion in vitro using proHp-overexpressing SK-Hep1 liver cancer cells. The results of Western blotting, quantitative real-time RT-PCR, and immunocytochemistry indicated that proHp downregulated expression of mesenchymal marker and EMT regulator such as N-cadherin, vimentin, and twist, and upregulated expression of the epithelial marker E-cadherin. Compared with control cells, proHp-overexpressing cells exhibited high levels of ALK1/2/3 receptors and markedly increased Smad1/5 phosphorylation. Interestingly, proHp attenuated TGF-ß-induced expression of mesenchymal markers and Smad2/3 phosphorylation. It also significantly suppressed cell invasion and migration. Knockdown of Smad1/5 abolished the inhibitory effects of proHp on TGF-ß-stimulated Smad2/3 phosphorylation and mesenchymal marker expression. These findings indicate that proHp suppresses the TGF-ß-induced EMT and cell invasion in vitro by enhancing Smad1/5 activation via ALK1/2/3 receptors and thus suppressing the Smad2/3 signaling pathway in SK-Hep1 cells. This study suggests that proHp may prevent a de-differentiation of hepatic cells and induce a cell differentiation by regulating the Smad signaling pathway.


Assuntos
Haptoglobinas , Neoplasias Hepáticas , Proteínas Smad , Fator de Crescimento Transformador beta , Linhagem Celular Tumoral , Movimento Celular , Células Endoteliais/metabolismo , Transição Epitelial-Mesenquimal , Haptoglobinas/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Precursores de Proteínas/metabolismo , Transdução de Sinais , Proteínas Smad/metabolismo , Proteína Smad1/metabolismo , Proteína Smad3/metabolismo , Proteína Smad5/metabolismo , Fator de Crescimento Transformador beta/metabolismo
7.
Int J Stem Cells ; 15(2): 203-216, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34966003

RESUMO

Background and Objectives: Epidemiological investigations have shown positive correlations between increased diesel exhaust particles (DEP) in ambient air and adverse health outcomes. DEP are the major constituent of particulate atmospheric pollution and have been shown to induce proinflammatory responses both in the lung and systemically. Here, we report the effects of DEP exposure on the properties of human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs), including stemness, regeneration, and immunomodulation. Methods and Results: Non-apoptotic concentrations of DEP (10 µg/ml) inhibited the migration and osteogenic differentiation capacity of WJ-MSCs. Gene expression profiling showed that DEP increased intracellular reactive oxygen species (ROS) and expression of pro-inflammatory and metabolic-process-related genes including cFos. Furthermore, WJ-MSCs cultured with DEP showed impaired suppression of T cell proliferation that was reversed by inhibition of ROS or knockdown of cFos. ERK inhibition assay revealed that DEP-induced ROS regulated cFos through activation of ERK but not NF-κB signaling. Overall, low concentrations of DEP (10 µg/ml) significantly suppressed the stemness and immunomodulatory properties of WJ-MSCs through ROS/ERK/cFos signaling pathways. Furthermore, WJ-MSCs cultured with DEP impaired the therapeutic effect of WJ-MSCs in experimental colitis mice, but was partly reversed by inhibition of ROS. Conclusions: Taken together, these results indicate that exposure to DEP enhances the expression of pro-inflammatory cytokines and immune responses through a mechanism involving the ROS/ERK/cFos pathway in WJ-MSCs, and that DEP-induced ROS damage impairs the therapeutic effect of WJ-MSCs in colitis. Our results suggest that modulation of ROS/ERK/cFos signaling pathways in WJ-MSCs might be a novel therapeutic strategy for DEP-induced diseases.

8.
Photochem Photobiol ; 98(4): 949-957, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34808003

RESUMO

Edible bird's nest (EBN) is a nutritious food with many beneficial effects, including protecting cells against oxidation and infection due to wounds, bacteria or viruses. EBN has shown antiaging, anti-inflammatory and wound-healing properties in skin cells. Here, we investigated whether EBN has protective effects against photoaging, inflammation and immune-senescence in hairless mice treated with UVB irradiation. The skin thickness was lower in mice on an EBN diet than in mice treated with UVB alone. The level of hydration was significantly increased, while the index of transepidermal water loss decreased, in groups on the EBN diet. EBN also reduced erythema index in UVB-irradiated mice. At the molecular level, skin elasticity and antiaging are associated with high expression of elastin, collagen and filaggrin and low expression of the membrane metalloproteinases, MMP-1 and MMP-2. Inflammatory markers such as interleukins, IL-1ß and IL-6, and TNF-α decreased significantly in the EBN groups. Caspase-3, an important factor in the apoptotic pathway and in congenital and adaptive immune responses, decreased in the EBN groups. Moreover, EBN diminished the overexpression of immunoglobulin E and elevated mast cell counts in UVB-irradiated mice. Overall, these findings suggest that EBN protects skin against aging and alleviates inflammation in UVB-irradiated hairless mice.


Assuntos
Envelhecimento da Pele , Animais , Aves/metabolismo , Imunidade , Inflamação , Camundongos , Camundongos Pelados
9.
JAMA ; 326(3): 240-249, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34180947

RESUMO

Importance: In 2019, the US Food and Drug Administration (FDA) received a citizen petition indicating that ranitidine contained the probable human carcinogen N-nitrosodimethylamine (NDMA). In addition, the petitioner proposed that ranitidine could convert to NDMA in humans; however, this was primarily based on a small clinical study that detected an increase in urinary excretion of NDMA after oral ranitidine consumption. Objective: To evaluate the 24-hour urinary excretion of NDMA after oral administration of ranitidine compared with placebo. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, crossover clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) conducted in 18 healthy participants. The study began in June 2020, and the end of participant follow-up was July 1, 2020. Interventions: Participants were randomized to 1 of 4 treatment sequences and over 4 periods received ranitidine (300 mg) and placebo (randomized order) with a noncured-meats diet and then a cured-meats diet. The cured-meats diet was designed to have higher nitrites, nitrates (nitrate-reducing bacteria can convert nitrates to nitrites), and NDMA. Main Outcome and Measure: Twenty-four-hour urinary excretion of NDMA. Results: Among 18 randomized participants (median age, 33.0 [interquartile range {IQR}, 28.3 to 42.8] years; 9 women [50%]; 7 White [39%], 11 African American [61%]; and 3 Hispanic or Latino ethnicity [17%]), 17 (94%) completed the trial. The median 24-hour NDMA urinary excretion values for ranitidine and placebo were 0.6 ng (IQR, 0 to 29.7) and 10.5 ng (IQR, 0 to 17.8), respectively, with a noncured-meats diet and 11.9 ng (IQR, 5.6 to 48.6) and 23.4 ng (IQR, 8.6 to 36.7), respectively, with a cured-meats diet. There was no statistically significant difference between ranitidine and placebo in 24-hour urinary excretion of NDMA with a noncured-meats diet (median of the paired differences, 0 [IQR, -6.9 to 0] ng; P = .54) or a cured-meats diet (median of the paired differences, -1.1 [IQR, -9.1 to 11.5] ng; P = .71). No drug-related serious adverse events were reported. Conclusions and Relevance: In this trial that included 18 healthy participants, oral ranitidine (300 mg), compared with placebo, did not significantly increase 24-hour urinary excretion of NDMA when participants consumed noncured-meats or cured-meats diets. The findings do not support that ranitidine is converted to NDMA in a general, healthy population. Trial Registration: ClinicalTrials.gov Identifier: NCT04397445.


Assuntos
Dimetilnitrosamina/urina , Antagonistas dos Receptores H2 da Histamina/farmacocinética , Ranitidina/farmacocinética , Administração Oral , Adulto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Antagonistas dos Receptores H2 da Histamina/administração & dosagem , Humanos , Masculino , Placebos/farmacocinética , Ranitidina/administração & dosagem
10.
Artigo em Inglês | MEDLINE | ID: mdl-33916718

RESUMO

The purpose of this study was to evaluate the reliability and validity of a Korean version of the 20-item COVID-19 phobia tool, which was developed through a translation-reverse translation process. These data were collected from 226 persons using a self-reported questionnaire. Exploratory and confirmatory factor analyses were used to test construct validity. Finally, for 19 out of 20 items, the item-level convergence and differential validity were confirmed. In addition, the reliability and validity of the tool as a whole has been verified. For the subscales, Cronbach's α was 0.90 for psychological, 0.87 for psychosomatic, 0.86 for economic, and 0.87 for social. Appropriate reliability was confirmed. Correlations between the COVID-19 phobia tool and fear of COVID-19 confirmed validity. The Korean version of the COVID-19 phobia tool is an appropriate scale for measuring the fear of COVID-19 and relevant psychological characteristics. Therefore, future studies in areas such as health and nursing could use this tool as required.


Assuntos
COVID-19 , Transtornos Fóbicos , Humanos , Transtornos Fóbicos/diagnóstico , Psicometria , Reprodutibilidade dos Testes , República da Coreia , SARS-CoV-2 , Inquéritos e Questionários
12.
J Clin Pharmacol ; 60(6): 775-784, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31967340

RESUMO

Chemotherapy-induced nausea and vomiting (CINV) is a common treatment-related adverse event that negatively impacts the quality of life of cancer patients. During pediatric drug development, extrapolation of efficacy from adult to pediatric populations is a pathway that can minimize the exposure of children to unnecessary clinical trials, improve efficiency, and increase the likelihood of success in obtaining a pediatric indication. The acceptability of the use of extrapolation depends on a series of evidence-based assumptions regarding the similarity of disease, response to intervention, and exposure-response relationships between adult and pediatric patients. This study evaluated publicly available summaries of data submitted to the US Food and Drug Administration for drugs approved for CINV to assess the feasibility of extrapolation for future development programs. Extracted data included trial design, emetogenic potential of chemotherapy, primary end points, participant enrollment criteria, and antiemetic pharmacokinetics. Adult and pediatric clinical trial designs for assessment of efficacy and safety shared key design elements. Antiemetic drugs found to be efficacious in adults were also efficacious in pediatric patients. Systemic drug concentrations at approved doses were similar for ondansetron, granisetron, and aprepitant, but an exposure-response analysis of palonosetron in children suggested that higher palonosetron systemic exposure is necessary for the prevention of CINV in the pediatric population. For 5-hydroxytryptamine-3 and neurokinin-1 receptor antagonist antiemetic drugs, efficacy in adults predicts efficacy in children, supporting the extrapolation of effectiveness of an antiemetic product in children from adequate and well-controlled studies in adult patients with CINV.


Assuntos
Antieméticos/farmacocinética , Aprepitanto/farmacocinética , Granisetron/farmacocinética , Náusea/prevenção & controle , Ondansetron/farmacocinética , Palonossetrom/farmacocinética , Vômito/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antieméticos/administração & dosagem , Antineoplásicos/efeitos adversos , Aprepitanto/administração & dosagem , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Interpretação Estatística de Dados , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Feminino , Granisetron/administração & dosagem , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Antagonistas dos Receptores de Neurocinina-1/administração & dosagem , Antagonistas dos Receptores de Neurocinina-1/farmacocinética , Ondansetron/administração & dosagem , Palonossetrom/administração & dosagem , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration , Vômito/induzido quimicamente , Adulto Jovem
13.
J. Phys. Educ. (Maringá) ; 31: e3121, 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1134723

RESUMO

ABSTRACT The study examined offensive tactical actions performed by U-15 soccer players with different competitive contexts. 34 matches played by three different contexts of U-15 soccer clubs were used; brazilian national (BN), brazilian regional (BR), and italian national (IN). Five categories where used to analyze the soccer offensive actions: "number of players involved" (NJ), "ball touches" (NT), "passes" (NP), "corridor changes" (NTC), and "duration of ball possession" (TRA); the results were coded using Match Vision Studio® software. The BN presented higher values in all five offensive categories (p < 0.05) when compared to the IN. Multinomial regression evidenced relative contributions of NJ and NP on the chances of results in the BN. The increase of one player involved in the offensive action decreases by 84% the chances of "total success" with respect to "unsuccessful" (p < 0.05). The performance of each additional pass increases 4.9 times the chance of the play ending in "total success" and 4.7 times (p < 0.05) in "partial success" when compared to the "unsuccessful" category. The NJ in the action and the NP have a direct influence on the outcome of the offensive actions of the BN.


RESUMO O estudo examinou ações táticas ofensivas realizadas por jogadores de futebol sub-15 em diferentes contextos competitivos. Foram analisados 34 jogos disputados por clubes sub-15 de três diferentes contextos competitivos, sendo estes: brasileiro nacional (BN), brasileiro regional (BR) e italiano nacional (IN). Cinco categorias foram utilizadas para analisar as ações futebolísticas ofensivas: "número de jogadores envolvidos" (NJ), "toques sobre a bola" (NT), "passes" (NP), "mudanças de corredor" (NTC) e "duração da posse de bola". "(TRA); os resultados foram codificados usando o software Match Vision Studio®. O BN apresentou valores maiores nas cinco categorias ofensivas (p <0,05) quando comparado ao IN. A regressão multinominal evidenciou contribuições relativas de NJ e NP nas chances de resultados no BN. O aumento de um jogador envolvido na ação ofensiva diminuiu em 84% as chances de "êxito total" em relação a "sem êxito" (p <0,05). O desempenho de cada passe adicional aumentou em 4,9 vezes a chance da jogada terminar em "êxito total" e 4,7 vezes (p <0,05) em "êxito parcial" quando comparado à categoria "sem êxito". O NJ na ação e o NP tiveram influência direta no resultado das ações ofensivas do BN.


Assuntos
Humanos , Adolescente , Futebol , Adolescente , Esportes Juvenis , Jogos e Brinquedos , Esportes , Ensino , Eficiência , Desempenho Atlético , Atletas
14.
ACS Nano ; 13(10): 11453-11459, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31539228

RESUMO

Plasmonic molecules are building blocks of metallic nanostructures that give rise to intriguing optical phenomena with similarities to those seen in molecular systems. The ability to design plasmonic hybrid structures and molecules with nanometric resolution would enable applications in optical metamaterials and sensing that presently cannot be demonstrated, because of a lack of suitable fabrication methods allowing the structural control of the plasmonic atoms on a large scale. Here we demonstrate a wafer-scale "lithography-free" parallel fabrication scheme to realize nanogap plasmonic meta-molecules with precise control over their size, shape, material, and orientation. We demonstrate how we can tune the corresponding coupled resonances through the entire visible spectrum. Our fabrication method, based on glancing angle physical vapor deposition with gradient shadowing, permits critical parameters to be varied across the wafer and thus is ideally suited to screen potential structures. We obtain billions of aligned dimer structures with controlled variation of the spectral properties across the wafer. We spectroscopically map the plasmonic resonances of gold dimer structures and show that they not only are in good agreement with numerically modeled spectra, but also remain functional, at least for a year, in ambient conditions.

15.
PLoS One ; 14(4): e0216289, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31034502

RESUMO

A potential role of haptoglobin in arterial restructuring has been suggested, and our previous study demonstrated that prohaptoglobin, the precursor of haptoglobin, stimulates endothelial angiogenesis. However, the mechanisms underlying the angiogenic effects of prohaptoglobin are still unclear. Here, we investigated angiogenic signaling induced by prohaptoglobin using human umbilical vein endothelial cells. Prohaptoglobin upregulated the expression of placental growth factor (PlGF), vascular endothelial growth factor (VEGF)-A, and VEGF receptor 1 and 2, and also induced cell migration and tube network formation. PlGF knockdown attenuated these angiogenic effects of prohaptoglobin. Furthermore, a transcription factor profiling assay indicated that Smad is involved in PlGF expression in response to prohaptoglobin. Transforming growth factor-ß1 (TGF-ß1) expression and Smad1/5 phosphorylation were also induced by prohaptoglobin treatment. Blockade of TGF-ß1 signaling using the TGF-ß receptor kinase inhibitor LY2109761 or Smad1/5 siRNA reduced the prohaptoglobin-induced PlGF expression and in vitro tube formation. Knockdown of the TGF-ß receptor ALK1, but not ALK5, with a specific siRNA blocked the Smad1/5 phosphorylation and PlGF expression induced by prohaptoglobin. These findings suggest that the angiogenic effects of prohaptoglobin are dependent on PlGF and mediated via a TGF-ß1-ALK1-Smad1/5-PlGF/VEGFR1-VEGF-A/VEGFR2 signaling pathway.


Assuntos
Receptores de Activinas Tipo II/metabolismo , Haptoglobinas/metabolismo , Neovascularização Fisiológica , Fator de Crescimento Placentário/metabolismo , Precursores de Proteínas/metabolismo , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima , Animais , Células COS , Chlorocebus aethiops , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Modelos Biológicos , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
16.
Int J Health Plann Manage ; 33(4): 1178-1188, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30160794

RESUMO

We explored the barriers to reporting patient safety incidents experienced by nurses and resident physicians while working in tertiary hospitals in South Korea. Sixteen in-depth interviews with 10 nurses and 6 resident physicians, all of whom had experienced patient safety incidents, were conducted. The interviews were analyzed using directed content analysis in accordance with a coding scheme developed in this study, which contains 4 categories (incidents and reporters, reporting procedures and systems, feedbacks, and reporting culture) and 9 subcategories. The barriers to reporting near-misses included the following: characteristics of the incident (eg, nonhazardous and high frequency), reporters' lack of knowledge, uncertainty, fear of blame, lack of role model, and inappropriate responses. Reporting adverse/sentinel events was also prevented by feelings of pressure or guilt, the fact that reporting was nonmandatory, and a belief that reporting was not part of the job. Some other barriers included lack of education, review process after reporting, lack of confidentiality when reporting, absence of feedback for reporting, unfair reporting based on work experience, perception of potential blame, and stigmatization resulting from it. In South Korea, a national system for reporting and learning of patient safety accidents has been operating since July 2016. To fully implement this system, it is necessary to encourage reporting at the institutional level. Our results might help reduce the barriers to patient safety incident reporting among nurses and resident physicians in tertiary hospitals in Korea through informing the development of improvement plans.


Assuntos
Documentação , Corpo Clínico Hospitalar/psicologia , Segurança do Paciente , Centros de Atenção Terciária , Documentação/métodos , Humanos , Entrevistas como Assunto , Cultura Organizacional , Pesquisa Qualitativa , República da Coreia
17.
JCI Insight ; 3(13)2018 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-29997291

RESUMO

The peripheral blood represents only a small fraction of the total number of lymphocytes in the body. To develop a more thorough understanding of T cell dynamics, including the effects of SIV/SHIV/HIV infection on immune cell depletion and immune reconstitution following combination antiretroviral therapy (cART), one needs to utilize approaches that allow direct visualization of lymphoid tissues. In the present study, noninvasive in vivo imaging of the CD4+ T cell pool has revealed that the timing of the CD4+ T cell pool reconstitution following initiation of ART in SIV-infected nonhuman primates (NHPs) appears seemingly stochastic among clusters of lymph nodes within the same host. At 4 weeks following initiation or interruption of cART, the changes observed in peripheral blood (PB) are primarily related to changes in the whole-body CD4 pool rather than changes in lymphocyte trafficking. Lymph node CD4 pools in long-term antiretroviral-treated and plasma viral load-suppressed hosts appear suboptimally reconstituted compared with healthy controls, while splenic CD4 pools appear similar between the 2 groups.


Assuntos
Antirretrovirais/farmacologia , Linfócitos T CD4-Positivos/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/diagnóstico por imagem , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Animais , Haplorrinos , Tecido Linfoide/imunologia , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vírus da Imunodeficiência Símia/imunologia , Vírus da Imunodeficiência Símia/patogenicidade , Crânio/diagnóstico por imagem , Baço/diagnóstico por imagem , Baço/imunologia , Carga Viral
18.
Contrast Media Mol Imaging ; 2018: 2461257, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29720923

RESUMO

We investigated the effect of shed antigen mesothelin on the tumor uptake of amatuximab, a therapeutic anti-mesothelin mAb clinically tested in mesothelioma patients. The B3 mAb targeting a nonshed antigen was also analyzed for comparison. The mouse model implanted with A431/H9 tumor, which expresses both shed mesothelin and nonshed Lewis-Y antigen, provided an ideal system to compare the biodistribution and PET imaging profiles of the two mAbs. Our study demonstrated that the tumor and organ uptakes of 89Zr-B3 were dose-independent when 3 doses, 2, 15, and 60 µg B3, were compared at 24 h after injection. In contrast, tumor and organ uptakes of 89Zr-amatuximab were dose-dependent, whereby a high dose (60 µg) was needed to achieve tumor targeting comparable to the low dose (2 µg) of 89Zr-B3, suggesting that shed mesothelin may affect amatuximab tumor targeting as well as serum half-life. The autoradiography analysis showed that the distribution of 89Zr-B3 was nonuniform with the radioactivity primarily localized at the tumor periphery independent of the B3 dose. However, the autoradiography analysis for 89Zr-amatuximab showed dose-dependent distribution profiles of the radiolabel; at 10 µg dose, the radiolabel penetrated toward the tumor core with its activity comparable to that at the tumor periphery, whereas at 60 µg dose, the distribution profile became similar to those of 89Zr-B3. These results suggest that shed antigen in blood may act as a decoy requiring higher doses of mAb to improve serum half-life as well as tumor targeting. Systemic mAb concentration should be at a severalfold molar excess to the shed Ag in blood to overcome the hepatic processing of mAb-Ag complexes. On the other hand, mAb concentration should remain lower than the shed Ag concentration in the tumor ECS to maximize tumor penetration by passing binding site barriers.


Assuntos
Anticorpos Monoclonais/farmacocinética , Zircônio , Animais , Antígenos de Neoplasias/imunologia , Linhagem Celular Tumoral , Micropartículas Derivadas de Células/imunologia , Proteínas Ligadas por GPI/imunologia , Meia-Vida , Xenoenxertos , Antígenos do Grupo Sanguíneo de Lewis/imunologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Mesotelina , Mesotelioma/imunologia , Mesotelioma/metabolismo , Mesotelioma Maligno , Camundongos , Radioisótopos , Distribuição Tecidual
19.
Med Sci Law ; 58(1): 16-24, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29065775

RESUMO

The aim of this study was to find out the risk factors through analysis of seven medical malpractice judgments related to fall injuries. The risk factors were analysed by using the framework that approaches falls from a systems perspective and comprised people, organisational or environmental factors, with each factor being comprised of subfactors. The risk factors found in each of the seven judgments were aggregated into one framework. The risk factors related to patients (i.e. the people factor) were age, pain, related disease, activities and functional status, urination state, cognitive function impairment, past history of fall, blood transfusion, sleep endoscopy state and uncooperative attitude. The risk factors related to the medical staff and caregivers (i.e. people factor) were observation negligence, no fall prevention activities and negligence in managing high-risk group for fall. Organisational risk factors were a lack of workforce, a lack of training, neglecting the management of the high-risk group, neglecting the management of caregivers and the absence of a fall prevention procedure. Regarding the environment, the risk factors were found to be the emergency room, chairs without a backrest and the examination table. Identifying risk factors is essential for preventing fall accidents, since falls are preventable patient-safety incidents. Falls do not happen as a result of a single risk factor. Therefore, a systems approach is effective to identify risk factors, especially organisational and environmental factors.


Assuntos
Acidentes por Quedas , Imperícia/legislação & jurisprudência , Segurança do Paciente/legislação & jurisprudência , Acidentes por Quedas/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Instalações de Saúde , Humanos , Pessoa de Meia-Idade , República da Coreia , Fatores de Risco
20.
Sensors (Basel) ; 17(11)2017 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-29165373

RESUMO

This paper presents a price-searching model in which a source node (Alice) seeks friendly jammers that prevent eavesdroppers (Eves) from snooping legitimate communications by generating interference or noise. Unlike existing models, the distributed jammers also have data to send to their respective destinations and are allowed to access Alice's channel if it can transmit sufficient jamming power, which is referred to as collaborative jamming in this paper. For the power used to deliver its own signal, the jammer should pay Alice. The price of the jammers' signal power is set by Alice and provides a tradeoff between the signal and the jamming power. This paper presents, in closed-form, an optimal price that maximizes Alice's benefit and the corresponding optimal power allocation from a jammers' perspective by assuming that the network-wide channel knowledge is shared by Alice and jammers. For a multiple-jammer scenario where Alice hardly has the channel knowledge, this paper provides a distributed and interactive price-searching procedure that geometrically converges to an optimal price and shows that Alice by a greedy selection policy achieves certain diversity gain, which increases log-linearly as the number of (potential) jammers grows. Various numerical examples are presented to illustrate the behavior of the proposed model.

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