Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Perianesth Nurs ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31495557

RESUMO

PURPOSE: This article describes the implementation and maintenance of obstructive sleep apnea (OSA) screening and capnography monitoring. DESIGN: A quality improvement project. METHODS: A multidisciplinary team provided staff education to three perianesthesia care units. Using the STOP-Bang screening tool, five or more positive responses indicated high risk for OSA. A postanesthesia care unit audit tool tracked STOP-Bang scores, capnography use, hypoventilation events, nursing interventions, and respiratory complications. FINDINGS: Among 314 patients with OSA, 36% were identified as high risk. Nurses used capnography on 76% of OSA patients and were able to readily identify hypoventilation and intervene. Respiratory complications occurred in 10.8% (n = 34) requiring a higher level of care. Postimplementation, all six postanesthesia care units employ this best practice. CONCLUSIONS: Perianesthesia nurses found OSA screening and capnography easy to incorporate into nursing practice. This process can reduce respiratory complications in the surgical patient with OSA. An Evidence-Based Practice Fellowship Program facilitated this practice change.

2.
Eat Disord ; : 1-19, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31314685

RESUMO

Suicidal ideation is a serious mental health concern reported by adolescents. Despite understanding of increased suicidal ideation in patients with eating disorders (EDs) and obesity, few studies have compared how disordered eating (bingeing, vomiting and over exercising) is associated with suicidal ideation in clinical and non-clinical samples of youth across the ED and weight spectrum. The present study aimed to 1) comparatively examine rates of suicidal ideation and disordered eating behaviors in clinical samples of youth with EDs, complex obesity, or from the community, and 2) examine whether disordered eating was associated with suicidal ideation above and beyond age, body mass index, diagnosis, treatment-seeking status, and depressive symptoms in large samples of males vs. females in an attempt to understand whether these behaviors should lead to concern regarding suicidal ideation. Data from charts on treatment-seeking adolescents diagnosed with either an ED (N = 315), severe complex obesity (N = 212), and from the community (N = 3036) were pooled together for comparative purposes. Results showed that suicidal ideation was higher in youth seeking treatment for an ED (50.2%) and obesity (23.7%) as compared to youth from the community (13%). Binary logistic regression analyses revealed that vomiting (OR = 1.73 for females, 8.17 for males) and over-exercising (OR = 1.47 for females, 1.68 for males) was significantly associated with suicidal ideation in both males and females. Findings underscore the importance of screening for suicidal ideation in youth who report vomiting or over-exercising despite diagnostic presentation, age, weight, or treatment setting.

3.
Ann Biomed Eng ; 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31342334

RESUMO

Ventricular Assist Devices (VADs) provide continuous mechanical circulatory support during in- and out-of-hospital care. However, limitations of the external wearable components influence patient quality of life. There is insufficient understanding of the issues with such components that combines a holistic viewpoint from both human factors and user (including patient and caregiver) experience perspectives. This paper comprehensively details the issues with VAD wearable systems and proposes a way for human-centered design to bridge the gap, addressing such issues synergistically. Through the review the authors investigated: the user issues caused by wearable components of VADs, and how human factors issues correlate to the VAD user experience. A Boolean search ("ventricular assist" AND "human factors" AND "experience") for peer-reviewed studies published between 2008 and 2018 returned 338 titles, with 35 relevant studies selected using a PRISMA process for inclusion in cross-study analysis and synthesis. This paper provides design recommendations for the issues found in the literature. Four key focus areas to inform the future design of VAD wearable components were identified-'Power Supply', 'Wearability and Travel Freedom', 'The Female Experience' and 'Intuitive Handling'. Using design to drive innovation could result in VAD wearable components which better meet or exceed users' quality of life goals.

4.
Nat Commun ; 10(1): 2825, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31249299

RESUMO

The formation of stomata and leaf mesophyll airspace must be coordinated to establish an efficient and robust network that facilitates gas exchange for photosynthesis, however the mechanism by which this coordinated development occurs remains unclear. Here, we combine microCT and gas exchange analyses with measures of stomatal size and patterning in a range of wild, domesticated and transgenic lines of wheat and Arabidopsis to show that mesophyll airspace formation is linked to stomatal function in both monocots and eudicots. Our results support the hypothesis that gas flux via stomatal pores influences the degree and spatial patterning of mesophyll airspace formation, and indicate that this relationship has been selected for during the evolution of modern wheat. We propose that the coordination of stomata and mesophyll airspace pattern underpins water use efficiency in crops, providing a target for future improvement.


Assuntos
Células do Mesofilo/química , Células do Mesofilo/metabolismo , Estômatos de Plantas/química , Estômatos de Plantas/metabolismo , Arabidopsis/química , Arabidopsis/metabolismo , Gases/metabolismo , Porosidade , Triticum/química , Triticum/metabolismo , Água/metabolismo
5.
J Exp Bot ; 70(18): 4737-4748, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31172183

RESUMO

Wheat is a staple crop, frequently cultivated in water-restricted environments. Improving crop water-use efficiency would be desirable if grain yield can be maintained. We investigated whether a decrease in wheat stomatal density via the manipulation of epidermal patterning factor (EPF) gene expression could improve water-use efficiency. Our results show that severe reductions in stomatal density in EPF-overexpressing wheat plants have a detrimental outcome on yields. However, wheat plants with a more moderate reduction in stomatal density (i.e. <50% reduction in stomatal density on leaves prior to tillering) had yields indistinguishable from controls, coupled with an increase in intrinsic water-use efficiency. Yields of these moderately reduced stomatal density plants were also comparable with those of control plants under conditions of drought and elevated CO2. Our data demonstrate that EPF-mediated control of wheat stomatal development follows that observed in other grasses, and we identify the potential of stomatal density as a tool for breeding wheat plants that are better able to withstand water-restricted environments without yield loss.

6.
ASAIO J ; 65(8): 855-863, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30575626

RESUMO

This article seeks to review and analyze the emergence of digital channels designed for ventricular assist device (VAD) patients, caregivers, and practitioners and to understand how such digital channels support the user experience of VAD implantation. Following a content analysis methodology, the authors investigated 16 digital channels designed for VAD patients, caregivers, and practitioners, with data being analyzed thematically. Competitor Positioning Matrix diagrams were created to visually represent the landscape of digital channels that support VAD stakeholders. These matrices identified opportunities and potential areas for improvement in future VAD digital channel design, with an emphasis on interactivity coupled with intelligence and focus along the various stages of the VAD patient journey. Innovation in digital channels has the potential to reduce burden on all users by enabling communication, self-management, and remote monitoring. Digital channels can be information enhanced for point of care, function as a decision support tools or be used to empower patient-caregiver pairs to be more sufficient with self-management, while enabling communication with their practitioner.

7.
Artigo em Inglês | MEDLINE | ID: mdl-30241320

RESUMO

Newly arrived migrants to the EU/EEA (arrival within the past five years), as well as other migrant groups in the region, might be under-immunised and lack documentation of previous vaccinations, putting them at increased risk of vaccine-preventable diseases circulating in Europe. We therefore performed a systematic review conforming to PRISMA guidelines (PROSPERO CRD42016045798) to explore: (i) interventions that improve vaccine uptake among migrants; and (ii) cost-effectiveness of vaccination strategies among this population. We searched MEDLINE, Embase, CINAHL, and Cochrane Database of Systematic Reviews (CDSR) between 1 January 2006 to 18 June 2018. We included three primary intervention studies performed in the EU/EEA or high-income countries and one cost effectiveness study relevant to vaccinations in migrants. Intervention studies showed small but promising impact only on vaccine uptake with social mobilization/community outreach, planned vaccination programs and education campaigns. Targeting migrants for catch-up vaccination is cost effective for presumptive vaccination for diphtheria, tetanus, and polio, and there was no evidence of benefit of carrying out pre-vaccination serological testing. The cost-effectiveness is sensitive to the seroprevalence and adherence to vaccinations of the migrant. We conclude that scarce but direct EU/EEA data suggest social mobilization, vaccine programs, and education campaigns are promising strategies for migrants, but more research is needed. Research should also study cost effectiveness of strategies. Vaccination of migrants should continue to be a public heath priority in EU/EEA.

8.
Artigo em Inglês | MEDLINE | ID: mdl-30050868

RESUMO

Cyclic-di-GMP (c-di-GMP) contributes to the regulation of processes required by the Lyme disease (LD) spirochetes to complete the tick-mammal enzootic cycle. Our understanding of the effector mechanisms of c-di-GMP in the Borrelia is evolving. While most LD spirochete isolates encode a single PilZ domain containing c-di-GMP receptor designated as PlzA, genome analyses have revealed that a subset encode a second PilZ domain protein (PlzB). The c-di-GMP binding potential of PlzB, and its role in LD spirochete biology, have not been investigated. To determine if PlzB binds c-di-GMP, plzB from B. burgdorferi isolate ZS7 was PCR amplified, cloned, and recombinant protein generated. PlzB bound c-di-GMP but not other nucleotides, indicating a specific binding interaction. To determine if PlzA and PlzB are functionally synonymous, a series of allelic-exchange gene deletion and cis-complemented strains were generated in the B. burgdorferi B31 background. B. burgdorferi B31-ΔplzA was competent to infect Ixodes scapularis larvae but not mice when delivered by either needle or tick feeding. B. burgdorferi B31-ΔplzA also displayed an atypical motility phenotype. Complementation in cis of B. burgdorferi B31-ΔplzA with plzA (B31-plzA KI) restored wild-type (wt) phenotype. However, a strain complemented in cis with plzB (B31-plzB KI) did not. The data presented here are consistent with an earlier study that demonstrated that PlzA plays an essential role in spirochete survival in the mammalian environment. We add to our understanding of the c-di-GMP regulatory network by demonstrating that while PlzB binds c-di-GMP, it is not functionally synonymous with PlzA. The absence of plzB from most strains suggests that it is not required for survival. One possibility is that cells that harbor both PlzA and PlzB might have enhanced biological fitness or increased virulence.

9.
J Nurs Care Qual ; 33(3): 213-220, 2018 Jul/Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29035906

RESUMO

Delirium is a potentially modifiable fall risk factor, but few studies address the effects of delirium programs on falls. Beginning in 2011, we implemented a nursing-driven hospitalwide delirium program targeting improvements in risk identification, prevention, detection, and treatment. Over the course of the program, delirium falls decreased from 0.91 to 0.50 per patient day (P = .0002). A decrease in overall falls was also noted (P = .0007).


Assuntos
Acidentes por Quedas/prevenção & controle , Delírio/diagnóstico , Delírio/prevenção & controle , Delírio/terapia , Avaliação em Enfermagem/métodos , Acidentes por Quedas/estatística & dados numéricos , Idoso , Registros Eletrônicos de Saúde/organização & administração , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Masculino , Recursos Humanos de Enfermagem no Hospital/educação , Equipe de Assistência ao Paciente/organização & administração , Fatores de Risco
10.
Plant Physiol ; 174(2): 776-787, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28461401

RESUMO

The epidermal patterning factor (EPF) family of secreted signaling peptides regulate the frequency of stomatal development in model dicot and basal land plant species. Here, we identify and manipulate the expression of a barley (Hordeum vulgare) ortholog and demonstrate that when overexpressed HvEPF1 limits entry to, and progression through, the stomatal development pathway. Despite substantial reductions in leaf gas exchange, barley plants with significantly reduced stomatal density show no reductions in grain yield. In addition, HvEPF1OE barley lines exhibit significantly enhanced water use efficiency, drought tolerance, and soil water conservation properties. Our results demonstrate the potential of manipulating stomatal frequency for the protection and optimization of cereal crop yields under future drier environments.


Assuntos
Secas , Hordeum/fisiologia , Proteínas de Plantas/genética , Estômatos de Plantas/fisiologia , Desidratação , Regulação da Expressão Gênica de Plantas , Hordeum/genética , Hordeum/crescimento & desenvolvimento , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas
11.
J Infect Dis ; 215(7): 1156-1166, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28329034

RESUMO

Background: Rapid diagnostic tests (RDTs) are an important tool for malaria diagnosis, with most using antibodies against Plasmodium falciparum histidine-rich protein 2 (PfHRP2). Reports of P. falciparum lacking this protein are increasing, creating a problem for diagnosis of falciparum malaria in locations without quality-assured microscopy. Methods: An agent-based stochastic simulation model of P. falciparum transmission was used to investigate the selective pressure exerted on parasite populations by use of RDTs for diagnosis of symptomatic cases. The model considered parasites with normal, reduced, or no PfHRP2, and diagnosis using PfHRP2-only or combination RDTs. Results: Use of PfHRP2-only RDTs in communities where a PfHRP2-negative parasite was introduced during the simulation resulted in transmission of the parasite in >80% of cases, compared with <30% for normal or PfHRP2-reduced parasites. Using PfHRP2-only RDTs in the presence of PfHRP2-negative parasites caused an increase in prevalence, reduced RDT positivity within symptomatic patients but no change in the number of antimalarial treatments due to false-negative RDT results. Diagnosis with PfHRP2/Pf-Plasmodium lactate dehydrogenase combination RDTs did not select for PfHRP2-negative parasites. Conclusions: The use of PfHRP2-only RDTs is sufficient to select P. falciparum parasites lacking this protein, thus posing a significant public health problem, which could be moderated by using PfHRP2/Pf-Plasmodium lactate dehydrogenase combination RDTs.

12.
Pathog Dis ; 74(8)2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27852620

RESUMO

The c-di-GMP network of Borrelia burgdorferi, a causative agent of Lyme disease, consists of Rrp1, a diguanylate cyclase/response regulator; Hpk1, a histidine kinase; PdeA and PdeB, c-di-GMP phosphodiesterases; and PlzA, a PilZ domain c-di-GMP receptor. Borrelia hermsii, a causative agent of tick-borne relapsing fever, possesses a putative c-di-GMP regulatory network that is uncharacterized. While B. burgdorferi requires c-di-GMP to survive within ticks, the associated effector mechanisms are poorly defined. Using site-directed mutagenesis, size exclusion chromatography, isothermal titration calorimetry and fluorescence resonance energy transfer, we investigate the interaction of c-di-GMP with the Borrelia PilZ domain-containing Plz proteins: B. burgdorferi PlzA and B. hermsii PlzC. The Plz proteins were determined to be monomeric in their apo and holo forms and to bind c-di-GMP with high affinity with a 1:1 stoichiometry. C-di-GMP binding induced structural rearrangements in PlzA and PlzC. C-di-GMP binding proved to be dependent on positive charge at R145 of the PilZ domain motif, R145xxxR. Comparative sequence analyses led to the identification of Borrelia consensus sequences for the PilZ domain signature motifs. This study provides insight into c-di-GMP:Plz receptor interaction and identifies a possible switch mechanism that may regulate Plz protein effector functions.


Assuntos
Proteínas de Bactérias/metabolismo , GMP Cíclico/análogos & derivados , Doença de Lyme/microbiologia , Febre Recorrente/microbiologia , Spirochaetaceae/metabolismo , Substituição de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Borrelia burgdorferi/genética , Borrelia burgdorferi/metabolismo , GMP Cíclico/metabolismo , Humanos , Mutação , Ligação Proteica , Conformação Proteica , Multimerização Proteica , Spirochaetaceae/genética
13.
Curr Biol ; 25(20): 2709-16, 2015 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-26455301

RESUMO

An integral part of global environment change is an increase in the atmospheric concentration of CO2 ([CO2]) [1]. Increased [CO2] reduces leaf stomatal apertures and density of stomata that plays out as reductions in evapotranspiration [2-4]. Surprisingly, given the importance of transpiration to the control of terrestrial water fluxes [5] and plant nutrient acquisition [6], we know comparatively little about the molecular components involved in the intracellular signaling pathways by which [CO2] controls stomatal development and function [7]. Here, we report that elevated [CO2]-induced closure and reductions in stomatal density require the generation of reactive oxygen species (ROS), thereby adding a new common element to these signaling pathways. We also show that the PYR/RCAR family of ABA receptors [8, 9] and ABA itself are required in both responses. Using genetic approaches, we show that ABA in guard cells or their precursors is sufficient to mediate the [CO2]-induced stomatal density response. Taken together, our results suggest that stomatal responses to increased [CO2] operate through the intermediacy of ABA. In the case of [CO2]-induced reductions in stomatal aperture, this occurs by accessing the guard cell ABA signaling pathway. In both [CO2]-mediated responses, our data are consistent with a mechanism in which ABA increases the sensitivity of the system to [CO2] but could also be explained by requirement for a CO2-induced increase in ABA biosynthesis specifically in the guard cell lineage. Furthermore, the dependency of stomatal [CO2] signaling on ABA suggests that the ABA pathway is, in evolutionary terms, likely to be ancestral.


Assuntos
Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Dióxido de Carbono/metabolismo , Transdução de Sinais , Estômatos de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
14.
PLoS One ; 9(12): e115494, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25545393

RESUMO

Babesia microti and Borrelia burgdorferi, the respective causative agents of human babesiosis and Lyme disease, are maintained in their enzootic cycles by the blacklegged tick (Ixodes scapularis) and use the white-footed mouse (Peromyscus leucopus) as primary reservoir host. The geographic range of both pathogens has expanded in the United States, but the spread of babesiosis has lagged behind that of Lyme disease. Several studies have estimated the basic reproduction number (R0) for B. microti to be below the threshold for persistence (<1), a finding that is inconsistent with the persistence and geographic expansion of this pathogen. We tested the hypothesis that host coinfection with B. burgdorferi increases the likelihood of B. microti transmission and establishment in new areas. We fed I. scapularis larva on P. leucopus mice that had been infected in the laboratory with B. microti and/or B. burgdorferi. We observed that coinfection in mice increases the frequency of B. microti infected ticks. To identify the ecological variables that would increase the probability of B. microti establishment in the field, we integrated our laboratory data with field data on tick burden and feeding activity in an R0 model. Our model predicts that high prevalence of B. burgdorferi infected mice lowers the ecological threshold for B. microti establishment, especially at sites where larval burden on P. leucopus is lower and where larvae feed simultaneously or soon after nymphs infect mice, when most of the transmission enhancement due to coinfection occurs. Our studies suggest that B. burgdorferi contributes to the emergence and expansion of B. microti and provides a model to predict the ecological factors that are sufficient for emergence of B. microti in the wild.


Assuntos
Babesia microti/patogenicidade , Babesiose/transmissão , Borrelia burgdorferi/patogenicidade , Animais , Coinfecção/microbiologia , Coinfecção/parasitologia , Ixodes/microbiologia , Ixodes/parasitologia , New England , Peromyscus/microbiologia , Peromyscus/parasitologia
15.
J Hosp Med ; 9(10): 658-62, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25130651

RESUMO

BACKGROUND: We hypothesized that delirium contributes to combative behavior requiring intervention in hospitalized patients. Delirium identification would therefore potentially provide an opportunity for prevention and early identification of patients at risk, thereby improving safety for patients and staff. OBJECTIVE: To determine whether delirium is associated with combative behavior requiring intervention in a general hospital population. DESIGN: Case control study. SETTING: A 336-bed, nonuniversity, teaching hospital serving adults in the Pacific Northwest. PATIENTS: One hundred twenty consecutive hospitalized patients with combative behavior requiring intervention compared to 159 randomly selected inpatient control subjects, all from 2011. INTERVENTION: Bivariate statistics were used to compare demographics; diagnoses; presence of delirium, dementia, substance use, other psychiatric diagnosis; medications; hospital length of stay; and discharge disposition. We used stepwise logistic regression to determine the association of combative behavior requiring intervention with delirium after adjustment for covariates. RESULTS: Delirium preceding the combative behavior was present in 50% (60/120) of patients with combative behavior requiring intervention compared to 16% (26/159) of controls (P < 0.001). Combative-behavior patients were hospitalized longer (9.4 vs 4.5 days, P < 0.001), and were more likely to be discharged to a skilled nursing facility (26%, 31/120) or to leave against medical advice (10%, 12/120, P < 0.001). Delirium was strongly associated with combative behavior requiring intervention, after adjustment (odds ratio: 3.8, 95% confidence interval: 2.0-7.3, P < 0.001). CONCLUSION: Delirium is strongly associated with combative behavior requiring intervention, which poses a significant safety risk for patients and staff.


Assuntos
Agressão , Delírio/epidemiologia , Delírio/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Hospitais de Ensino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Pessoa de Meia-Idade , Entorpecentes/administração & dosagem , Alta do Paciente/estatística & dados numéricos , Fatores de Risco
16.
J Interpers Violence ; 28(5): 1088-108, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23071083

RESUMO

The court system is a central part of the societal response to intimate partner violence (IPV), and is a frequently used source of help for victims. The concept of therapeutic jurisprudence suggests that the court should be evaluated not just for its potential effect on recidivism, but for its impact on the well-being of all those who participate in it, and IPV scholars suggest that empowerment is a key component of any therapeutic intervention for victims. Research in these areas is limited by the lack of a standard method for examining victim experience in the court system. This article describes the development and piloting of a 23-item measure designed to address this gap. The pilot sample included 157 victims of IPV seeking civil protection orders (CPOs). Exploratory factor analysis yielded 5 factors: Negative Impact, Positive Impact, Fear, Validation, and Network Impact. Validation was most strongly correlated with global satisfaction with the court process. Implications and applications for work in therapeutic jurisprudence and empowerment are discussed.


Assuntos
Atitude , Mulheres Maltratadas , Função Jurisdicional , Maus-Tratos Conjugais/legislação & jurisprudência , Inquéritos e Questionários , Mulheres Maltratadas/psicologia , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Projetos Piloto , Poder (Psicologia) , Psicometria , Reprodutibilidade dos Testes , Maus-Tratos Conjugais/prevenção & controle , Estados Unidos
17.
J Invest Dermatol ; 131(5): 1139-48, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21150922

RESUMO

Longwave UVA is an independent class I carcinogen. A complete understanding of UVA-induced DNA damage and how this damage is processed in skin cells is therefore of utmost importance. A particular question that has remained contentious is whether UVA induces DNA double-strand breaks (DSBs), either directly or through processing of other types of DNA damage, such as recombination repair of replication forks stalled at DNA photoproducts. We therefore studied activation of the recombination repair pathway by solar available doses of UVA and assessed formation of DNA DSBs in primary skin fibroblasts. We found that, unlike ionizing radiation or UVB, UVA does not activate the Fanconi anemia/BRCA DNA damage response pathway or the "recombinase" RAD51 in primary skin fibroblasts. The fact that this pathway mediates recombination repair of DNA DSBs suggests that DNA DSBs are not formed by UVA. This is further supported by findings that UVA did not induce DNA DSBs, as assayed by neutral single-cell electrophoresis or by formation of γ-H2AX nuclear foci, considered the most sensitive assay for DNA DSBs. The lack of sufficient evidence for formation of DNA DSBs underlines the pivotal role of UVA-induced DNA photoproducts in UVA mutagenesis and carcinogenesis.


Assuntos
Quebras de DNA de Cadeia Dupla/efeitos da radiação , Reparo do DNA/efeitos da radiação , Fibroblastos/efeitos da radiação , Recombinação Genética/efeitos da radiação , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Técnicas de Cultura de Células , Histonas/efeitos da radiação , Humanos , Masculino , Recombinases/efeitos da radiação
18.
Cancer Res ; 66(23): 11140-7, 2006 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-17145857

RESUMO

Recombination repair plays an important role in the processing of DNA double-strand breaks (DSB) and DNA cross-links, and has been suggested to be mediated by the activation of the Fanconi anemia (FA)/BRCA pathway. Unlike DNA damage generated by ionizing radiation or DNA cross-linking, UV light-induced DNA damage is not commonly thought to require recombination for processing, as UV light does not directly induce DSBs or DNA cross-links. To elucidate the role of recombination repair in the cellular response to UV, we studied the FA/BRCA pathway in primary skin cells exposed to solar-simulated light. UV-induced monoubiquitination of the FANCD2 protein and formation of FANCD2 nuclear foci confirmed the activation of the pathway by UV light. This was only observed when cells were irradiated during S phase and was not caused by directly UV-induced DSBs. UV-exposed cells did not exhibit FANCD2 nuclear foci once they entered mitosis or when growth-arrested. In addition, UV-induced nuclear foci of the recombination proteins, RAD51 and BRCA1, colocalized with FANCD2 foci. We suggest that in response to UV light, when nucleotide excision repair failed to repair, or when translesional DNA synthesis failed to bypass UV-induced DNA photoproducts, the FA/BRCA pathway mediates the recombination repair of replication forks stalled at DNA photoproducts as a third line of defense.


Assuntos
Proteína BRCA1/metabolismo , Reparo do DNA/efeitos da radiação , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Transdução de Sinais/efeitos da radiação , Raios Ultravioleta , Ciclo Celular/efeitos da radiação , Núcleo Celular/metabolismo , Núcleo Celular/efeitos da radiação , Células Cultivadas , Relação Dose-Resposta à Radiação , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Humanos , Immunoblotting , Imuno-Histoquímica , Recém-Nascido , Masculino , Rad51 Recombinase/metabolismo , Recombinação Genética/efeitos da radiação , Fatores de Tempo
19.
Vaccine ; 20(31-32): 3658-67, 2002 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-12399193

RESUMO

As new vaccines are developed, novel adjuvants may play an important role in eliciting an effective immune response. We evaluated the safety and adjuvant properties of monophosphoryl lipid A (MPL in 129 healthy toddlers immunized with two doses of nine-valent pneumococcal-CRM(197) protein conjugate vaccine (PCV9) combined with 10, 25, or 50 micro g of MPL with or without alum (AlPO(4)). Vaccine-specific humoral and cell-mediated responses were examined following the second dose of study vaccine. All doses of MPL were well-tolerated and a dose-dependent effect of MPL on specific cellular responses was observed. The 10 micro g MPL dose significantly enhanced CRM(197)-specific T-cell proliferation (P=0.02) and interferon-gamma (INF-gamma) production (P=0.009) compared to responses of controls who received PCV9 with AlPO(4). In contrast, CRM(197)-specific T-cell proliferation and interferon-gamma production of the 50 micro g MPL/AlPO(4) group were decreased when compared to controls although these differences did not reach statistical significance. IL-5 and IL-13 responses after immunization showed a similar pattern with increased production in the 10 micro g MPL group and decreased production in the 50 micro g MPL/AlPO(4) group compared to controls. There were no differences in serum IgG antibody concentrations to the nine vaccine pneumococcal capsular polysaccharides and carrier protein between the MPL-containing and control vaccine groups. These findings demonstrate a dose-dependent effect of MPL on T-helper cell type 1 (TH-1) responses to the carrier protein and also suggest an effect on T-helper cell type 2 (TH-2) responses.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Proteínas de Bactérias/administração & dosagem , Lipídeo A/análogos & derivados , Lipídeo A/administração & dosagem , Polissacarídeos Bacterianos/administração & dosagem , Linfócitos T Auxiliares-Indutores/imunologia , Adjuvantes Imunológicos/efeitos adversos , Compostos de Alumínio/administração & dosagem , Compostos de Alumínio/efeitos adversos , Compostos de Alumínio/imunologia , Compostos de Alumínio/farmacologia , Anticorpos Antibacterianos/biossíntese , Antígenos de Bactérias/administração & dosagem , Antígenos de Bactérias/efeitos adversos , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/efeitos adversos , Proteínas de Bactérias/imunologia , Pré-Escolar , Citocinas/biossíntese , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Celular/imunologia , Imunoglobulina G/biossíntese , Lactente , Lipídeo A/efeitos adversos , Lipídeo A/imunologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Masculino , Fosfatos/administração & dosagem , Fosfatos/efeitos adversos , Fosfatos/imunologia , Fosfatos/farmacologia , Polissacarídeos Bacterianos/efeitos adversos , Polissacarídeos Bacterianos/imunologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA