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1.
J Nurs Scholarsh ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33829653

RESUMO

PURPOSE: The number of multicultural families has increased globally, and Korea has also witnessed a surge. Along with the various challenges experienced by these families, a child with a disability can pose additional challenges. In-depth knowledge about resilience factors among multicultural families of children with disabilities is important. The aim of this study was to examine relationships between family demands, family appraisals, family problem solving and coping, family resources, and family adaptation in multicultural families of children with disabilities in Korea as perceived by married immigrants. DESIGN: This study was based on a secondary analysis of national survey data in 2015 and 2018 in Korea. METHODS: A total of 256 multicultural families who have children with disabilities participated. Family demands were identified by examining marital conflict, cultural differences, marital status, and public assistance recipient households. Family appraisal was assessed by how the family perceived the married immigrant's culture. Family problem solving and coping were examined by how actively a married immigrant participated in social activities. Family resources were assessed by examining Korean language competency and the health status of immigrants. Family adaptation was identified by how immigrants perceived their life satisfaction. Path analysis was used to assess the factors. FINDINGS: Family demands had a direct impact on family resources and family adaptation. Family appraisal had a direct impact on family adaptation. Family resources mediated the effect of family demands on family adaptation. CONCLUSIONS: This study demonstrated that although a multicultural family of a child with a disability struggles with family demands, if the family receives positive resources from family members, they can adapt well. Current findings can be used to develop interventions that can foster greater resilience among families. CLINICAL RELEVANCE: This study provides evidence that nurses can target modifiable family aspects, including immigrants' health and family perceptions of immigrants' cultures identified in this study to enhance the immigrant and family adaptation.

3.
Cancers (Basel) ; 13(5)2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33804486

RESUMO

PURPOSE: Granulocyte colony-stimulating factor (G-CSF) and hypoxia modulate the tumour immune microenvironment. In model systems, hypoxia-induced carbonic anhydrase IX (CAIX) has been associated with G-CSF and immune responses, including M2 polarization of macrophages. We investigated whether these associations exist in human breast cancer specimens, their relation to breast cancer subtypes, and clinical outcome. METHODS: Using validated protocols and prespecified scoring methodology, G-CSF expression on carcinoma cells and CD163 expression on tumour-associated macrophages were assayed by immunohistochemistry and applied to a tissue microarray series of 2960 primary excision specimens linked to clinicopathologic, biomarker, and outcome data. RESULTS: G-CSFhigh expression showed a significant positive association with ER negativity, HER2 positivity, presence of CD163+ M2 macrophages, and CAIX expression. In univariate analysis, G-CSFhigh phenotype was associated with improved survival in non-luminal cases, although the CAIX+ subset had a significantly adverse prognosis. A significant positive association was observed between immune checkpoint biomarkers on tumour-infiltrating lymphocytes and both G-CSF- and CAIX-expressing carcinoma cells. Immune checkpoint biomarkers correlated significantly with favourable prognosis in G-CSFhigh/non-luminal cases independent of standard clinicopathological features. CONCLUSIONS: The prognostic associations linking G-CSF to immune biomarkers and CAIX strongly support their immunomodulatory roles in the tumour microenvironment.

4.
Assessment ; : 10731911211005183, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33794674

RESUMO

Both personality impairment and maladaptive-range traits are necessary for diagnosis in the alternative model of personality disorder. We clarified personality impairment-trait connections using measures of the interpersonal problems circumplex and personality traits among adult outpatients (N = 351) with major depressive disorder receiving cognitive therapy (CT). The trait scales' circumplex projections were summarized by elevation (correlations with general interpersonal problems), amplitude (specific relations to the circumplex dimensions of dominance and affiliation), and angle (predominant orientation in the two-dimensional circumplex). Most trait scales showed hypothesized circumplex relations, including substantive elevation (e.g., negative temperament, mistrust), amplitude (e.g., aggression, detachment), and expected angles (e.g., positive temperament and manipulativeness oriented toward overly nurturant/intrusive or domineering/vindictive problems, respectively), that were stable across time during CT. These results revealed meaningful and consistent impairment-trait connections, even during CT when mean depressive affect decreased substantially.

5.
eNeuro ; 8(2)2021.
Artigo em Inglês | MEDLINE | ID: mdl-33707203

RESUMO

Drugs of abuse engage overlapping but distinct molecular and cellular mechanisms to enhance dopamine (DA) signaling in the mesocorticolimbic circuitry. DA neurons of the ventral tegmental area (VTA) are key substrates of drugs of abuse and have been implicated in addiction-related behaviors. Enhanced VTA DA neurotransmission evoked by drugs of abuse can engage inhibitory G-protein-dependent feedback pathways, mediated by GABAB receptors (GABABRs) and D2 DA receptors (D2Rs). Chemogenetic inhibition of VTA DA neurons potently suppressed baseline motor activity, as well as the motor-stimulatory effect of cocaine and morphine, confirming the critical influence of VTA DA neurons and inhibitory G-protein signaling in these neurons on this addiction-related behavior. To resolve the relative influence of GABABR-dependent and D2R-dependent signaling pathways in VTA DA neurons on behavioral sensitivity to drugs of abuse, we developed a neuron-specific viral CRISPR/Cas9 approach to ablate D2R and GABABR in VTA DA neurons. Ablation of GABABR or D2R did not impact baseline physiological properties or excitability of VTA DA neurons, but it did preclude the direct somatodendritic inhibitory influence of GABABR or D2R activation. D2R ablation potentiated the motor-stimulatory effect of cocaine in male and female mice, whereas GABABR ablation selectively potentiated cocaine-induced activity in male subjects only. Neither D2R nor GABABR ablation impacted morphine-induced motor activity. Collectively, our data show that cocaine and morphine differ in the extent to which they engage inhibitory G-protein-dependent feedback pathways in VTA DA neurons and highlight key sex differences that may impact susceptibility to various facets of addiction.

6.
Cell Host Microbe ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33662277

RESUMO

Determining which immunological mechanisms contribute to the development of broad neutralizing antibodies (bNAbs) during HIV-1 infection is a major goal to inform vaccine design. Using samples from a longitudinal HIV-1 acute infection cohort, we found key B cell determinants within the first 14-43 days of viremia that predict the development of bNAbs years later. Individuals who develop neutralization breadth had significantly higher B cell engagement with the autologous founder HIV envelope (Env) within 1 month of initial viremia. A higher frequency of founder-Env-specific naive B cells was associated with increased B cell activation and differentiation and predictive of bNAb development. These data demonstrate that the initial B cell interaction with the founder HIV Env is important for the development of broadly neutralizing antibodies and provide evidence that events within HIV acute infection lead to downstream functional outcomes.

8.
Int J Cancer ; 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33586179

RESUMO

High-dose (HD) cisplatin remains the standard of care with chemoradiation for locally advanced oropharyngeal cancer (OPC). Cooperative group trials mandate bolus-HD (100 mg/m2 × 1 day, every 3 weeks) cisplatin administration at the beginning of the week to optimize radiosensitization-a requirement which may be unnecessary. This analysis evaluates the impact of chemotherapy administration day of week (DOW) on outcomes. We also report our institutional experience with an alternate dosing schedule, split-HD (50 mg/m2 × 2 days, every 3 weeks). We retrospectively reviewed 435 definitive chemoradiation OPC patients from 10 December 2001 to 23 December 2014. Those receiving non-HD cisplatin regimens or induction chemotherapy were excluded. Data collected included DOW, dosing schedule (bolus-HD vs split-HD), smoking, total cumulative dose (TCD), stage, Karnofsky Performance Status, human papillomavirus status and creatinine (baseline, peak and posttreatment baseline). Local failure (LF), regional failure (RF), locoregional failure (LRF), distant metastasis (DM), any failure (AF, either LRF or DM) and overall survival (OS) were calculated from radiation therapy start. Median follow-up was 8.0 years (1.8 months-17.0 years). DOW, dosing schedule and TCD were not associated with any outcomes in univariable or multivariable regression models. There was no statistically significant difference in creatinine or association with TCD in split-HD vs bolus-HD. There was no statistically significant association between DOW and outcomes, suggesting that cisplatin could be administered any day. Split-HD had no observed differences in outcomes, renal toxicity or TCD compared to bolus-HD cisplatin. Our data suggest that there is some flexibility of when and how to give HD cisplatin compared to clinical trial mandates.

9.
Gynecol Oncol ; 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33597092

RESUMO

OBJECTIVE: Gaps in access to appropriate cancer care, and associated cancer mortality, have widened across socioeconomic groups. We examined whether demographic and socioeconomic factors influenced receipt of adjuvant radiation therapy (RT) in patients with high-risk, early-stage endometrial cancer. METHODS: A retrospective study cohort was selected from 349,404 endometrial carcinoma patients from the National Cancer Database in whom adjuvant RT would be recommended per national guidelines. The study included surgically treated patients with endometrioid endometrial cancer with one of the following criteria: 1) FIGO 2009 stage IB, grade 1/2 disease, age ≥ 60 years; 2) stage IB, grade 3 disease; or 3) stage II disease. Logistic regression analysis was performed to identify factors associated with omission of adjuvant RT. Association between adjuvant RT, covariables, and overall survival (OS) was assessed with multivariable Cox proportional hazards models. RESULTS: 19,594 patients were eligible for analysis; 47% did not receive adjuvant RT. Omission of adjuvant RT was more prevalent among African-American, Hispanic, and Asian compared to non-Hispanic white patients (OR 0.79, 95%CI: 0.69-0.91; OR 0.75, 95%CI: 0.64-0.87; OR 0.75, 95%CI: 0.60-0.94, respectively). Lower median household income of patient's area of residence, lack of health insurance, treatment at non-academic hospitals, farther distance to treatment facilities, and residence in metropolitan counties were associated with omission of adjuvant RT. Such omission was independently associated with worse OS (HR1.43, p < 0.001). CONCLUSION: Adjuvant RT is omitted in 47% of patients with early-stage, high-risk endometrial cancer, which is associated with poor access to appropriate, high-quality care and worse outcome.

10.
Head Neck ; 43(4): 1056-1062, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33606323

RESUMO

BACKGROUND: Proton beam radiation therapy (PBRT) has dosimetric advantages compared to photon radiation therapy for the treatment of major salivary gland tumors (MSGTs). METHODS: Patients with non-metastatic MSGTs treated at a single proton therapy center from October 2013 to October 2018 were retrospectively reviewed. RESULTS: Sixty-eight patients with MSGTs were included and the most common site and histology were the parotid gland (75.0%) and adenoid cystic carcinoma (22.1%), respectively. The 3-year rates of locoregional control, progression-free survival, and overall survival were 95.1% (95% CI: 89.9%-100.0%), 80.7% (70.2%-92.7%), and 96.1% (95% CI: 90.9%-100.0%), respectively. CONCLUSION: In a large cohort of MSGTs treated with PBRT, the rates of locoregional control were high in short-term follow-up and treatment was well tolerated.

11.
Int Ophthalmol ; 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33609201

RESUMO

PURPOSE: To investigate aqueous cytokine levels in association with hemorrhage in proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus. METHODS: Sixty-six eyes with treatment-naïve PDR, including 26 hemorrhagic and 40 nonhemorrhagic eyes were included in this institutional study. Aqueous humor levels of interleukin (IL)-1b, IL-6, IL-8, IL-10, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), and soluble VEGF receptor-1 were obtained by multiplex bead assay. Visual acuity and hemorrhage area measurements were obtained, and correlations between cytokine levels and hemorrhage were identified. RESULTS: Levels of MCP-1, TNF-α, and VEGF were higher in hemorrhagic eyes (1506.77 vs. 2131.31 pg/mL, 0.43 vs. 0.63 pg/mL, and 103.96 vs. 206.96 pg/mL; P = 0.050, 0.022, and 0.027, respectively). The levels of IL-8, MCP-1, TNF-α, and VEGF showed positive correlation with visual acuity (P = 0.019, 0.015, 0.001, and 0.014, respectively). The hemorrhage area revealed positive correlation with TNF-α and VEGF levels (P = 0.001 and < 0.001, respectively). CONCLUSION: The presence and amount of hemorrhage in PDR were associated not only with VEGF concentration, but also with the levels of certain inflammatory cytokines, suggesting a role of both VEGF and inflammation in hemorrhagic eyes.

12.
Bioorg Med Chem ; 31: 115969, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33422910

RESUMO

P38α/MAPK14 is intracellular signalling regulator involved in biosynthesis of inflammatory mediator cytokines (TNF-α, IL-1, IL-6, and IL-1b), which induce the production of inflammatory proteins (iNOS, NF-kB, and COX-2). In this study, drug repurposing strategies were followed to repositioning of a series of B-RAF V600E imidazol-5-yl pyridine inhibitors to inhibit P38α kinase. A group 25 reported P38α kinase inhibitors were used to build a pharmacophore model for mapping the target compounds and proving their affinity for binding in P38α active site. Target compounds were evaluated for their potency against P38α kinase, compounds 11a and 11d were the most potent inhibitors (IC50 = 47 nM and 45 nM, respectively). In addition, compound 11d effectively inhibited the production of proinflammatory cytokinesTNF-α, 1L-6, and 1L-1ß in LPS-induced RAW 264.7 macrophages with IC50 values of 78.03 nM, 17.6 µM and 82.15 nM, respectively. The target compounds were tested for their anti-inflammatory activity by detecting the reduction of Nitric oxide (NO) and prostaglandin (PGE2) production in LPS-stimulated RAW 264.7 macrophages. Compound 11d exhibited satisfied inhibitory activity of the production of PGE2 and NO with IC50 values of 0.29 µM and 0.61 µM, respectively. Molecular dynamics simulations of the most potent inhibitor 11d were carried out to illustrate its conformational stability in the binding site of P38α kinase.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33430335

RESUMO

The purpose of this scoping review was to identify the family and child quality of life variables that have been studied in relation to one another in children with Down syndrome, the frequency with which different relationships have been studied, and the extent to which family variables were the focus of the research aims. A literature search was conducted to find studies published between January 2007 and June 2018. The initial search yielded 2314 studies; of these, 43 were selected for a final review. Researchers most often addressed family resources and family problem-solving and coping concerning child personal development and physical well-being. Little attention to child emotional well-being was observed, with none considering family appraisal of child emotional well-being. The relationship between family variables and child QoL rarely was the primary focus of the study. Methodologically, most reviewed studies used cross-sectional designs, were conducted in North America and based on maternal report. From future research considering the issues found in this review, healthcare providers can obtain an in-depth understanding of relationships between children and family variables.


Assuntos
Síndrome de Down , Qualidade de Vida , Adaptação Psicológica , Criança , Estudos Transversais , Humanos , América do Norte
14.
Environ Monit Assess ; 193(1): 35, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33409602

RESUMO

Birds can serve as effective biomonitors of air pollution, yet few studies have quantified external particulate matter accumulation on bird feathers. Biomonitoring of airborne elemental carbon (EC) is of critical significance because EC is a component of particulate matter with adverse effects on air quality and human health. To assess their effectiveness for use in EC monitoring, we compared EC accumulation on bird feathers at two sites that differed in vehicular traffic volume in an urban environment within the Dallas-Fort Worth Metropolitan Area, USA. Moulted flight feathers from domestic chickens were experimentally exposed to ambient EC pollution for 5 days in two urban microenvironments 1.5 km distant from each other that differed in traffic volume--adjacent to an interstate highway and a university campus bus stop. Feathers near the highway accumulated approximately eight times more EC (307 ± 34 µg m-2 day-1), on average, than feathers near the bus stop (40 ± 9 µg m-2 day-1). These findings indicate that EC accumulation on feathers varies over short distances within urban areas and that bird feathers potentially can be used for biomonitoring airborne EC.


Assuntos
Poluentes Atmosféricos , Plumas , Poluentes Atmosféricos/análise , Animais , Carbono/análise , Galinhas , Monitoramento Ambiental , Plumas/química , Humanos , Material Particulado/análise , Emissões de Veículos/análise
15.
Personal Ment Health ; 15(1): 26-31, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33336513

RESUMO

This commentary on Livesley's paper in this special issue on International Classification of Diseases (ICD)-11's personality disorder (PD) section addresses each of four issues that Livesley claims are impeding progress towards an evidence-based system for the classification of personality pathology. I focus my commentary on the third issue, but also comment briefly on the others. Regarding, first, the complexity of personality pathology and, second, problematic assumptions about the nature of personality pathology, I contend that Livesley's comments are accurate, but omit that the fundamental impediment is the refusal of the Diagnostic and Statistical Manual of Mental Disorders (DSM) establishment to allow the official classification to reflect the reality of personality pathology that he describes, in contrast to its acceptance in the ICD-11. In response to Livesley's third claim that a viable alternative to categorical diagnosis is not available, I take issue with various aspects of his assertions and develop arguments that the ICD-11 PD model provides a useful, although admittedly imperfect, system. Finally, I agree with Livesley that the revision processes for official classifications are conservative and open to non-scientific influences, but maintain that whereas the Diagnostic and Statistical Manual of Mental Disorders establishment held fast to the status quo, the ICD-11 PD Working Group made considerable progress towards a valid PD diagnostic system. © 2020 John Wiley & Sons, Ltd.

16.
Child Care Health Dev ; 47(1): 85-93, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32997835

RESUMO

BACKGROUND: To date, investigations of quality of life (QoL) in children with Down syndrome (DS) are rather limited. The purpose of this study was twofold: to examine QoL in children with DS and to explore possible differences in the QoL by age and gender. METHODS: A cross-sectional study of 211 parents of children with DS was conducted using an online survey that included a consent form, a demographic questionnaire and the English version of KidsLife, which is a measure of children's QoL. RESULTS: Our results demonstrated moderate or favourable levels of QoL except for the emotional well-being domain among children with DS. The children's QoL showed no variance by gender. However, emotional and material well-being, interpersonal relations and social inclusion varied by age. CONCLUSIONS: The current findings provide important evidence that will help healthcare, educational and social services professionals to understand the multiple aspects of QoL in children with DS and support parents in their efforts to ensure the child's QoL. The results also point to the need to develop interventions aimed at improving QoL in those areas where children with DS are at increased risk for poorer QoL.

17.
Ann Am Thorac Soc ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33284738

RESUMO

RATIONALE: There are limited data on mechanical discontinuation practices in Asia. OBJECTIVES: To document self-reported mechanical discontinuation practices and determine whether there is clinical equipoise regarding protocolized weaning amongst Asian Intensive Care specialists. METHODS: Survey using a validated questionnaire, distributed using a snowball method to Asian Intensive Care specialists. RESULTS: Of 2,967 invited specialists from 20 territories, 2,074 (69.9%) took part. 60.5% were from China. 42% of all respondents worked in Intensive Care units where respiratory therapists were present. 78.9% used a spontaneous breathing trial as the initial weaning step. 44.3% frequently-always used pressure support alone, 53.4% intermittent spontaneous breathing trials with pressure support in between and 19.8% synchronized intermittent mandatory ventilation with pressure support as a weaning mode. 56.3% routinely stopped feeds before extubation. 71.5% generally followed a sedation protocol or guideline. 61.8% worked in an Intensive Care unit with a weaning protocol. Of these 78.2% frequently-always followed the protocol. Multivariate analysis involving a modified Poisson regression analysis showed that working in an Intensive Care unit with a weaning protocol and frequently-always following it was positively associated with upper-middle income territory, university affiliated hospital, or in an Intensive Care unit that employed respiratory therapists; and negatively with low-income or low-middle income territory or a public hospital. There was no significant association with "in house" intensivist at night, multidisciplinary Intensive Care unit, closed Intensive Care unit or nurse-patient ratio. There was heterogenity in agreement/disagreement with the statement "evidence clearly supports protocolized weaning over non-protocolized weaning". CONCLUSIONS: A substantial minority of Asian Intensive Care specialists do not wean patients in accordance with best available evidence or current guidelines. There is clinical equipoise regarding the benefit of protocolized weaning.

18.
PLoS Pathog ; 16(12): e1009101, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33290394

RESUMO

The RV144 vaccine efficacy clinical trial showed a reduction in HIV-1 infections by 31%. Vaccine efficacy was associated with stronger binding antibody responses to the HIV Envelope (Env) V1V2 region, with decreased efficacy as responses wane. High levels of Ab-dependent cellular cytotoxicity (ADCC) together with low plasma levels of Env-specific IgA also correlated with decreased infection risk. We investigated whether B cell priming from RV144 vaccination impacted functional antibody responses to HIV-1 following infection. Antibody responses were assessed in 37 vaccine and 63 placebo recipients at 6, 12, and 36 months following HIV diagnosis. The magnitude, specificity, dynamics, subclass recognition and distribution of the binding antibody response following infection were different in RV144 vaccine recipients compared to placebo recipients. Vaccine recipients demonstrated increased IgG1 binding specifically to V1V2, as well as increased IgG2 and IgG4 but decreased IgG3 to HIV-1 Env. No difference in IgA binding to HIV-1 Env was detected between the vaccine and placebo recipients following infection. RV144 vaccination limited the development of broadly neutralizing antibodies post-infection, but enhanced Fc-mediated effector functions indicating B cell priming by RV144 vaccination impacted downstream antibody function. However, these functional responses were not associated with clinical markers of disease progression. These data reveal that RV144 vaccination primed B cells towards specific binding and functional antibody responses following HIV-1 infection.

19.
Transfusion ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33269472

RESUMO

BACKGROUND: Recruitment of committed unrelated hematopoietic stem cell donors from the most-needed demographics remains a challenge for donor recruitment organizations worldwide. Multimedia resources are gaining attention as a modality to support recruitment efforts; however, there is a lack of guidance for the development of such tools. This qualitative study explores the perspectives of eligible stem cell donors on an educational whiteboard video about stem cell donation, generating insights into how whiteboard videos and related multimedia may be optimized for donor recruitment. STUDY DESIGN AND METHODS: Eight semistructured focus groups were conducted with 38 potential donors from the most-needed demographics (young, male, and non-Caucasian) after they had watched a 3.5-minute whiteboard video explaining key concepts in stem cell donation (https://youtu.be/V4fVBtxnWfM). Constructivist grounded theory was used to identify themes and to develop a framework for understanding participants' preferred features of recruitment multimedia. RESULTS: Participants identified a range of features contributing to the effectiveness of recruitment multimedia, adding that the whiteboard video is an effective, integrated, and readily accessible format for supporting donor recruitment. Topics that participants felt are important to address include knowledge gaps regarding donation procedures, concerns about donor safety, and the particular need for specific donor demographics. Suggested avenues for improvement include the addition of donor/recipient/patient personal experiences, attention-grabbing hooks, and a call to action including opportunities for further learning. CONCLUSIONS: Several considerations were generated to inform the development of future multimedia for donor education/recruitment and are relevant to donor recruitment organizations worldwide.

20.
JAMA Oncol ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33270082
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