RESUMO
BACKGROUND: Oral language skills provide the foundation for formal education, yet many children enter school with language weaknesses. This study evaluated the efficacy of a new language enrichment programme, the Nuffield Early Language Intervention-Preschool (NELI Preschool), delivered to children in the year before they enter formal education. METHODS: We conducted a preregistered cluster randomised controlled trial in 65 nursery schools in England (https://doi.org/10.1186/ISRCTN29838552). NELI Preschool consists of a 20-week whole-class language enrichment programme delivered by a teacher each day for 20 min. In addition, children with the weakest language skills in each class are allocated to receive additional targeted support delivered by classroom assistants (whole-class + targeted). The language skills of all children (n = 1,586) in participating classrooms were assessed using the LanguageScreen automated app (https://oxedandassessment.com/languagescreen/). Settings were then randomly allocated to an intervention or control group. The children with the weakest language in each class (whole-class + targeted children n = 438), along with four randomly selected children in each class allocated to the whole-class only programme (n = 288) were individually tested on a range of language measures. RESULTS: Children receiving NELI Preschool made larger gains than children in the control group on an oral language latent variable (whole-class children d = .26; whole-class + targeted children d = .16). CONCLUSIONS: This study provides good evidence that whole-class intervention delivered in preschool can produce educationally significant improvements in children's language skills. The intervention is scaleable and relatively low cost. These findings have important implications for educational and social policy.
Assuntos
Intervenção Educacional Precoce , Humanos , Pré-Escolar , Masculino , Feminino , Intervenção Educacional Precoce/métodos , Inglaterra , Desenvolvimento da Linguagem , Terapia da Linguagem/métodos , Transtornos do Desenvolvimento da Linguagem/terapia , Escolas Maternais , Linguagem InfantilRESUMO
INTRODUCTION: Aortic graft infection remains a considerable clinical challenge, and it is unclear which variables are associated with adverse outcomes among patients undergoing partial resection. METHODS: A retrospective, multi-institutional study of patients who underwent partial resection of infected aortic grafts from 2002 to 2014 was performed using a standard database. Baseline demographics, comorbidities, operative, and postoperative variables were recorded. The primary outcome was mortality. Descriptive statistics, Kaplan-Meier (KM) survival analysis, and Cox regression analysis were performed. RESULTS: One hundred fourteen patients at 22 medical centers in 6 countries underwent partial resection of an infected aortic graft. Seventy percent were men with median age 70 years. Ninety-seven percent had a history of open aortic bypass graft: 88 (77%) patients had infected aortobifemoral bypass, 18 (16%) had infected aortobiiliac bypass, and 1 (0.8%) had an infected thoracic graft. Infection was diagnosed at a median 4.3 years post-implant. All patients underwent partial resection followed by either extra-anatomic (47%) or in situ (53%) vascular reconstruction. Median follow-up period was 17 months (IQR 1, 50 months). Thirty-day mortality was 17.5%. The KM-estimated median survival from time of partial resection was 3.6 years. There was no significant survival difference between those undergoing in situ reconstruction or extra-anatomic bypass (Pâ¯=â¯0.6). During follow up, 72% of repairs remained patent and 11% of patients underwent major amputation. On univariate Cox regression analysis, Candida infection was associated with increased risk of mortality (HR 2.4; Pâ¯=â¯0.01) as well as aortoenteric fistula (HR 1.9, Pâ¯=â¯0.03). Resection of a single graft limb only to resection of abdominal (graft main body) infection was associated with decreased risk of mortality (HR 0.57, Pâ¯=â¯0.04), as well as those with American Society of Anesthesiologists classification less than 3 (HR 0.35, Pâ¯=â¯0.04). Multivariate analysis did not reveal any factors significantly associated with mortality. Persistent early infection was noted in 26% of patients within 30 days postoperatively, and 39% of patients were found to have any post-repair infection during the follow-up period. Two patients (1.8%) were found to have a late reinfection without early persistent postoperative infection. Patients with any post-repair infection were older (67 vs. 60 years, Pâ¯=â¯0.01) and less likely to have patent repairs during follow up (59% vs. 32%, Pâ¯=â¯0.01). Patients with aortoenteric fistula had a higher rate of any post-repair infection (63% vs. 29%, P < 0.01) CONCLUSION: This large multi-center study suggests that patients who have undergone partial resection of infected aortic grafts may be at high risk of death or post-repair infection, especially older patients with abdominal infection not isolated to a single graft limb, or with Candida infection or aortoenteric fistula. Late reinfection correlated strongly with early persistent postoperative infection, raising concern for occult retained infected graft material.
Assuntos
Aorta/cirurgia , Implante de Prótese Vascular/efeitos adversos , Prótese Vascular/efeitos adversos , Remoção de Dispositivo , Procedimentos Endovasculares/efeitos adversos , Infecções Relacionadas à Prótese/cirurgia , Idoso , Implante de Prótese Vascular/instrumentação , Implante de Prótese Vascular/mortalidade , Remoção de Dispositivo/efeitos adversos , Remoção de Dispositivo/mortalidade , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/mortalidade , Reoperação , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: It is widely believed that increasing parental involvement can improve children's educational outcomes although we lack good evidence for such claims. This study evaluated the effectiveness of a parent-delivered early language enrichment programme. METHODS: We conducted a randomised controlled trial (RCT) with 208 preschool children and their parents living in socially diverse areas in the United Kingdom. Families were allocated to an oral language programme (N = 103) or an active control programme targeting motor skills (N = 105). Parents delivered the programmes to their child at home in daily 20-min sessions over 30 weeks of teaching. RESULTS: Children receiving the language programme made significantly larger gains in language (d = .21) and narrative skills (d = .36) than children receiving the motor skills programme at immediate posttest. Effects on language were maintained 6 months later (d = .34), and at this point, the language group also scored higher on tests of early literacy (d values=.35 and .42). There was no evidence that the movement programme improved motor skills. CONCLUSIONS: This study provides evidence for the effectiveness of a parent-delivered language enrichment programme. Further large-scale evaluations of the programme are needed to confirm and extend these findings.
Assuntos
Intervenção Educacional Precoce/métodos , Desenvolvimento da Linguagem , Idioma , Alfabetização , Destreza Motora/fisiologia , Avaliação de Resultados em Cuidados de Saúde , Pais , Pré-Escolar , Feminino , Humanos , Masculino , Pais/educação , Reino UnidoRESUMO
BACKGROUND: The practice of antenatal breast expression (ABE) has been proposed as a strategy to promote successful breastfeeding. Although there has been some focus on the evaluation of the effects of ABE in promotion of breastfeeding, little or no evidence exists on women's experiences of ABE or opinions on ABE, particularly amongst overweight or obese women. METHODS: This study aimed to explore women's knowledge, practices and opinions of ABE, and any differences within the overweight and obese subgroups. A cross-sectional survey was undertaken using an online questionnaire distributed by a maternity user group representative via social media. Quantitative data were analysed using Chi-square and Fisher's exact tests in SPSS. Simple thematic analysis was used for the qualitative data. RESULTS: A total of 688 responses were analysed; the sample represented a group of breastfeeding mothers, of whom 64.5% had heard of ABE, 8.2% had been advised to do ABE, and 14.2% had undertaken ABE. Of the women who had been advised to do ABE, 67.9% had complied. Most participants (58.6%) were unsure if ABE was a good idea; however 80.9% would consider doing ABE if it was found to be helpful to prepare for breastfeeding. Women in the overweight or obese subgroups were significantly more likely to have heard of ABE (p < 0.001), and positive opinion of ABE also increased with higher BMI groups. The qualitative data demonstrated participants felt ABE may be beneficial when mother or baby have medical problems, and in preparation for breastfeeding, but highlighted their concerns that it may interfere with nature and be harmful, and that they wanted more information and knowledge about ABE. CONCLUSIONS: Amongst women who have breastfed, many have heard of ABE, compliance with advice to undertake ABE is relatively high, and ABE is considered an acceptable practice. Further investigation into the benefits and safety of ABE is warranted, to address the needs of childbearing women for evidence-based information about this practice. If the evidence base is established, overweight and obese pregnant women could be an important target group for this intervention.
Assuntos
Aleitamento Materno/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Educação de Pacientes como Assunto , Cuidado Pré-Natal/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Gravidez , Cuidado Pré-Natal/métodos , Pesquisa Qualitativa , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Prenatal alcohol exposure (PAE) can result in physical and neurocognitive deficits that are collectively termed "fetal alcohol spectrum disorders" (FASD). Although FASD is associated with lifelong intellectual disability, the mechanisms mediating the emergence of secondary mental health and physical disabilities are poorly understood. Based on our previous data showing that maternal ethanol (EtOH) exposure in mice resulted in an immediate reduction in cranially directed fetal blood flow, we hypothesized that such exposure would also result in persistent alterations in cranially directed blood flow in the prenatally alcohol-exposed (PAE) adult. We also hypothesized that PAE adults exposed to an acute cerebrovascular insult would exhibit more brain damage and neurobehavioral impairment compared to non-PAE adult controls. METHODS: Pregnant C57BL/6 mice were exposed to EtOH, 3 g/kg, or water by intragastric gavage. Blood flow in carotid, renal, and femoral arteries was assessed by ultrasound imaging in PAE and control adults at 3, 6, and 12 months of age. To mimic ischemic stroke in young adult populations, 3-month-old PAE and control animals were subject to transient middle cerebral artery occlusion (MCAo) and subsequently assessed for behavioral recovery, stroke infarct volume, and brain cytokine profiles. RESULTS: PAE resulted in a significant age-related decrease in blood acceleration in adult mice, specifically in the carotid artery. A unilateral transient MCAo resulted in equivalent cortico-striatal damage in both PAE and control adults. However, PAE adult mice exhibited significantly decreased poststroke behavioral recovery compared to controls. CONCLUSIONS: Our data collectively show that PAE adult mice exhibit a persistent, long-term loss of cranially directed blood flow, and decreased capacity to compensate for brain trauma due to acute-onset adult diseases like ischemic stroke.
Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Circulação Cerebrovascular/fisiologia , Etanol/toxicidade , Ataque Isquêmico Transitório/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Etanol/administração & dosagem , Feminino , Ataque Isquêmico Transitório/induzido quimicamente , Ataque Isquêmico Transitório/diagnóstico por imagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/diagnóstico por imagemRESUMO
PURPOSE: Oral language skills provide a critical foundation for formal education and especially for the development of children's literacy (reading and spelling) skills. It is therefore important for teachers to be able to assess children's language skills, especially if they are concerned about their learning. We report the development and standardization of a mobile app-LanguageScreen-that can be used by education professionals to assess children's language ability. METHOD: The standardization sample included data from approximately 350,000 children aged 3;06 (years;months) to 8;11 who were screened for receptive and expressive language skills using LanguageScreen. Rasch scaling was used to select items of appropriate difficulty on a single unidimensional scale. RESULTS: LanguageScreen has excellent psychometric properties, including high reliability, good fit to the Rasch model, and minimal differential item functioning across key student groups. Girls outperformed boys, and children with English as an additional language scored less well compared to monolingual English speakers. CONCLUSIONS: LanguageScreen provides an easy-to-use, reliable, child-friendly means of identifying children with language difficulties. Its use in schools may serve to raise teachers' awareness of variations in language skills and their importance for educational practice.
Assuntos
Testes de Linguagem , Aplicativos Móveis , Psicometria , Humanos , Criança , Aplicativos Móveis/normas , Masculino , Feminino , Testes de Linguagem/normas , Pré-Escolar , Reprodutibilidade dos Testes , Psicometria/instrumentação , Psicometria/normas , Psicometria/métodos , Linguagem Infantil , Transtornos do Desenvolvimento da Linguagem/diagnósticoRESUMO
It has long been established that school psychology practitioners experience high levels of burnout. As a means of preventing burnout among future practitioners, school psychology training programs are frequently encouraged to teach and model self-care to students. This is particularly important as the current generation of graduate students experience high levels of anxiety and depression, but there have been very few examples in the research literature of how training programs should teach self-care and whether it is actually effective. The current study presents results from an exploratory case study, which integrated self-care instruction into graduate school psychology curriculum with a small sample (N = 22) of first-year school psychology students across two separate cohorts. Students created written plans with self-care strategies that they attempted to implement over the course of their first semester in graduate school. A qualitative review of their plans and written reflections revealed that students described many sources of stress upon entry into training, and most needed to revise their strategies for coping as stresses changed during the semester. Overall, student reflections revealed that the self-care activities were helpful to meet the demands of their graduate education.
RESUMO
In collaboration with the American College of Veterinary Pathologists.
Assuntos
Patologia Veterinária , Médicos Veterinários , Animais , Humanos , Estados UnidosRESUMO
BACKGROUND: The cytologic diagnosis of inflammation on canine hepatic aspirates can be confounded by neutrophilic infiltrates in the liver of dogs with nodular regeneration, by extramedullary hematopoiesis, and by marked blood contamination. OBJECTIVES: We aimed to assess the association between neutrophil counts on hepatic cytology and the histopathologic diagnosis in dogs with hepatitis and non-inflammatory hepatopathy. We also sought to determine a cut-off value for the cytologic diagnosis of hepatitis. METHODS: In a retrospective blinded pilot study, three observers independently reviewed hepatic aspirates that had corresponding histopathologic examinations performed within 2 days. The number of neutrophils per 200 hepatocytes was determined and averaged among observers. Only neutrophils within or directly in contact with a cluster of ≥5 hepatocytes were counted, and only intact hepatocytes within an approximate monolayer were included. Data are presented as the median (range), and the Mann-Whitney U test is used to make comparisons between groups. RESULTS: Eighteen cases were included (13 hepatitis and five vacuolar hepatopathy). Aspirates with a histopathologic diagnosis of hepatitis had increased numbers of neutrophils compared with those of vacuolar hepatopathy (7.7 [0.3-18.3] vs 3.0 [1.0-5.3]; P = .038). Receiver operating characteristic curve analysis indicated that ≥6 neutrophils were 61.5% (CI 31.6%-86.1%) sensitive and 100% (CI 47.8%-100%) specific for identifying hepatitis. CONCLUSIONS: Liver aspirates from hepatitis cases have a higher number of neutrophils on cytology compared with those from vacuolar hepatopathy; however, larger studies, including those with dogs with other liver pathologies, are required. Identification of six or more neutrophils per 200 hepatocytes is highly suggestive of hepatitis.
Assuntos
Doenças do Cão , Hepatite , Hepatopatias , Animais , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Cães , Hepatopatias/veterinária , Neutrófilos/patologia , Projetos Piloto , Estudos RetrospectivosRESUMO
Antemortem diagnosis of neuroborreliosis in horses has been hindered by both the low sensitivity of PCR testing for Borrelia burgdorferi in CSF and the low specificity of serum:CSF ELISA ratios used to determine intrathecal antibody production against the bacterium. PCR testing of the CSF of an adult horse with acute neurologic disease for the B. burgdorferi flagellin gene was negative. However, we enriched B. burgdorferi DNA through nucleic acid hybrid capture, followed by next-generation sequencing, and identified B. burgdorferi in the CSF of the horse, confirming a diagnosis of neuroborreliosis.
Assuntos
Grupo Borrelia Burgdorferi , Borrelia burgdorferi , Doenças dos Cavalos , Doença de Lyme , Doenças do Sistema Nervoso , Animais , Anticorpos Antibacterianos , Borrelia burgdorferi/genética , Grupo Borrelia Burgdorferi/genética , Ensaio de Imunoadsorção Enzimática/veterinária , Genômica , Doenças dos Cavalos/diagnóstico , Cavalos , Doença de Lyme/diagnóstico , Doença de Lyme/veterinária , Doenças do Sistema Nervoso/veterináriaRESUMO
Evaluation and management of recumbent horses are challenging. Familiarity with disorders that can result in recumbency will facilitate more rapid diagnosis and more appropriate formulation of a prognosis. With rapid and appropriate diagnosis, appropriate treatment can be pursued and, with good nursing care, can result in a favorable outcome.
Assuntos
Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/terapia , Doenças do Sistema Nervoso/veterinária , Exame Neurológico/veterinária , Animais , Cavalos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/terapia , PrognósticoRESUMO
OBJECTIVE: To determine whether sublingual detomidine gel administration to horses would be effective in providing an appropriate degree of sedation and restraint to facilitate completion of veterinary and husbandry procedures under field conditions. DESIGN: Multicenter, prospective, randomized, blinded, placebo-controlled clinical study. ANIMALS: 270 client-owned horses known to require sedation or strong restraint to enable veterinary and husbandry procedures to be performed. PROCEDURES: Horses randomly received a single dose of detomidine gel (0.04 mg/kg [0.018 mg/lb]) or placebo gel administered sublingually. Horses were sedated to facilitate cleaning the prepuce, cutting of hair with electric clippers, hoof trimming or application of shoes, manual dental floating (ie, rasping or filing of the teeth to remove irregularities), nasogastric passage of a stomach tube or endoscope, and radiography. The primary determinant of efficacy was an assessment by a veterinarian on the ability or inability to successfully conduct the procedure. RESULTS: 171 horses met all the study protocol criteria. One hundred twenty-nine horses were treated with detomidine. The procedure was completed successfully for 76% (98/129) of the detomidine-treated horses, while the procedure was completed successfully for only 7% (3/42) of the placebo-treated horses. The percentage of horses in which the procedure was successfully completed was significantly different between detomidine-treated horses and placebo-treated horses. No serious adverse effects were reported. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine gel administered to horses sublingually at a dose of 0.04 mg/kg provided an appropriate degree of sedation and restraint to facilitate completion of veterinary and husbandry procedures in horses known to require sedation for such procedures.
Assuntos
Hipnóticos e Sedativos/uso terapêutico , Imidazóis/uso terapêutico , Administração Sublingual , Animais , Sedação Consciente/veterinária , Feminino , Hipnóticos e Sedativos/administração & dosagem , Imidazóis/administração & dosagem , MasculinoRESUMO
PURPOSE: The retinal degeneration (rd1) mouse undergoes a rapid loss of rod photoreceptors due to a defect in the cGMP-phosphodiesterase gene. We have previously demonstrated that dopamine (DA) antagonists or DA depletion blocks photoreceptor degeneration and that DA is necessary for photoreceptor degeneration in the rd1 mouse retinal organ culture model. Antagonists for either D1- or D2-family DA receptors are protective in rd1 organ cultures. METHODS: To determine whether photoreceptor survival can be increased in vivo in the rd1 mouse, we used both a pharmacological and a genetic approach. The pharmacological approach involved three techniques to administer 6-hydroxydopamine (6-OHDA) in an attempt to deplete DA in postnatal mouse retina in vivo. As a genetic alternative, DA receptor signaling was inactivated by crossbreeding rd1 mice to D1, D2, D4, and D5 knockout mice to create four lines of double mutants. RESULTS: Pharmacological DA depletion was incomplete due to the limiting size of the postnatal mouse eye and the lethality of systemic inhibition of DA signaling. In all four lines of double mutants, no increase in rod photoreceptor survival was observed. To determine whether protection of rd1 photoreceptors by inhibition of dopaminergic signaling is a result of conditions specific to the organ culture environment, we grew in vitro retinas from the four lines of double mutant mice for four weeks. Again, no increase in photoreceptor survival was seen. Finally, three triple mutants were generated that lacked two DA receptors (D1/D2; D1/D4; and D2/D4) on a rd1 background. In all three cases, rod photoreceptors were not protected from degeneration. CONCLUSIONS: The dramatic protection of rd1 rod photoreceptors by inhibition of DA signaling in organ culture has not been reproduced in vivo by either a pharmacological approach, due to technical limitations, or by genetic manipulations. The possible role of compensatory effects during retinal development in DA receptor deficient mice is considered.
Assuntos
Receptores Dopaminérgicos/deficiência , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/patologia , Animais , Animais Recém-Nascidos , Sobrevivência Celular , Camundongos , Técnicas de Cultura de Órgãos , Receptores Dopaminérgicos/metabolismoRESUMO
Human hunting activity and disturbance can significantly impact prey species through both consumptive and nonconsumptive effects. The nonconsumptive effects of rabbit hunting on Northern Bobwhite (Colinus virginianus; hereafter, bobwhite) are currently unknown. Increased perceived risk of predation by bobwhite during rabbit hunting events may elicit antipredator responses among bobwhite that impact fitness via changes in behavior that ultimately impact population growth.We estimated the nonconsumptive effects of rabbit hunting on bobwhite behavior using telemetry across varying rabbit hunting intensities. Movements were analyzed using Bayesian hierarchical modeling with a before-after-control-impact (BACI) design to determine the effect of rabbit hunting on bobwhite.We observed an overall reduction in bobwhite movement in the presence of rabbit hunting, with a 38% (Posterior Overlap = 0.01) increase in bobwhite step length in the absence of rabbit hunting. We also observed bobwhite maintaining closer proximity to hardwood and escape cover under high rabbit hunting intensity, with a 59% (Posterior Overlap = 0.03) increase in distance from hardwood and a 28% (Posterior Overlap = 0.14) increase in distance from escape cover when rabbit hunting was removed. Synthesis and applications. Heightened antipredator behavior through decreased movement may assist with bobwhite predator avoidance. However, decreased movement and increased use of poor habitats may also have negative effects as a result of reduced foraging time or increased susceptibility to other predators. Future research should attempt to quantify the effect of decreased movement on bobwhite fitness through the evaluation of foraging time and survival in order to continue to improve management efforts for the species.
RESUMO
BACKGROUND: Prognosis associated with lymphoma in horses is poorly characterized, and treatment is often palliative. Long-term outcome after chemotherapy for horses with lymphoma is not well documented. OBJECTIVE: To report long-term outcome of horses with lymphoma treated with chemotherapy. ANIMALS: Fifteen equids. METHODS: Retrospective case series. Medical record search and call for cases on the ACVIM listserv for horses treated with chemotherapy for lymphoma. RESULTS: Fifteen cases with adequate data were identified. Complete remission was achieved in 5 horses (33.3%), partial response was achieved in 9 equids (60%), and stable disease was achieved in 1 horse. Overall response rate was 93.3% (14/15). Overall median survival time was 8 months (range, 1-46 months). Nine horses experienced a total of 14 adverse effects attributable to chemotherapy. Adverse effects were graded according to the Veterinary Cooperative Oncology Group common terminology criteria for adverse events grading system (grade 1 alopecia, n = 2; grade 1 neutropenia, n = 2; grade 1 lymphopenia, n = 3; grade 1 lethargy, n = 1; grade 2 neurotoxicity, n = 1; grade 2 colic, n = 1; grade 1 hypersensitivity, n = 1; grade 2 hypersensitivity, n = 2; grade 5 hypersensitivity, n = 1). Higher grade adverse effects most commonly were associated with doxorubicin administration (n = 4), including 1 horse that died 18 hours post-administration. CONCLUSIONS AND CLINICAL IMPORTANCE: Chemotherapy can be used successfully for treatment of horses with lymphoma. Adverse effects, most commonly mild, occurred in approximately two-thirds of treated horses.
Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Linfoma/veterinária , Resultado do Tratamento , Animais , Equidae , Feminino , Cavalos , Linfoma/tratamento farmacológico , Masculino , Indução de Remissão , Estudos RetrospectivosRESUMO
In normal cells, aberrant oncogene expression leads to the accumulation of cytotoxic metabolites, including reactive oxygen species (ROS), which can cause oxidative DNA-damage and apoptosis as an intrinsic barrier against neoplastic disease. The c-Myc oncoprotein is overexpressed in many lymphoid cancers due to c-myc gene amplification and/or 8q24 chromosomal translocations. Intriguingly, p53 is a downstream target of c-Myc and hematological malignancies, such as adult T-cell leukemia/lymphoma (ATL), frequently contain wildtype p53 and c-Myc overexpression. We therefore hypothesized that p53-regulated pro-survival signals may thwart the cell's metabolic anticancer defenses to support oncogene-activation in lymphoid cancers. Here we show that the Tp53-induced glycolysis and apoptosis regulator (TIGAR) promotes c-myc oncogene-activation by the human T-cell leukemia virus type-1 (HTLV-1) latency-maintenance factor p30II, associated with c-Myc deregulation in ATL clinical isolates. TIGAR prevents the intracellular accumulation of c-Myc-induced ROS and inhibits oncogene-induced cellular senescence in ATL, acute lymphoblastic leukemia, and multiple myeloma cells with elevated c-Myc expression. Our results allude to a pivotal role for p53-regulated antioxidant signals as mediators of c-Myc oncogenic functions in viral and non-viral lymphoid tumors.
Assuntos
Carcinogênese , Regulação Viral da Expressão Gênica/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Oncogenes/fisiologia , Estresse Oxidativo/fisiologia , Proteínas dos Retroviridae/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Reguladoras de Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Monoéster Fosfórico Hidrolases , Espécies Reativas de Oxigênio , Proteínas dos Retroviridae/genéticaRESUMO
BACKGROUND: Phagocytic activity of neonatal foals has been reported to be similar to that of adult horses, but serum opsonization capacity develops with age and may be further altered when opsonins are consumed during infection. HYPOTHESIS: Phagocytosis, oxidative burst activity, and serum opsonization capacity in neonatal foals admitted to an intensive care unit are reduced in comparison with control foals. ANIMALS: Blood samples were collected from hospitalized neonatal foals and from control foals. Hospitalized foals were characterized as sick or septic on the basis of a sepsis score and received intravenous plasma transfusion. METHODS: Phagocytosis, oxidative burst activity, and serum opsonization capacity were tested with flow cytometric analysis. Serum immunoglobulin and complement component 3 concentrations were determined with radial immunodiffusion. Serum amyloid A concentration was assayed with a commercially available solid-phase Sandwich ELISA Kit. Data were analyzed with nonparametric and regression methods. Alpha was set at P = .05. RESULTS: Phagocytic functions of septic and sick foals were lower than control foals in the initial phase of the study (P = .01). Opsonization capacity was significantly higher when bacteria were opsonized with serum from septic (P = .029) and sick (P = .006) foals than from control foals on day 1. Opsonization capacity in septic foals was comparable with control foals on days 2 and 5. This effect was not accompanied by an increase in serum complement C3 or immunoglobulin G concentrations independently. CONCLUSIONS AND CLINICAL IMPORTANCE: Our results suggest that phagocytic function could be decreased in hospitalized foals. The synergistic effect of opsonic elements provided by plasma transfusion may sustain opsonization capacity during sepsis.
Assuntos
Doenças dos Cavalos/metabolismo , Proteínas Opsonizantes/sangue , Explosão Respiratória/fisiologia , Animais , Animais Recém-Nascidos , Complemento C3/metabolismo , Feminino , Doenças dos Cavalos/sangue , Cavalos , Imunoglobulinas/sangue , Unidades de Terapia Intensiva , Masculino , Proteínas Opsonizantes/metabolismo , Fagocitose , Sepse/sangue , Sepse/metabolismo , Proteína Amiloide A Sérica/metabolismoRESUMO
We have developed transgenic Chinese hamster V79 cell lines in order to examine the potential for a mouse aldo-keto reductase, AKR7A5, to protect against the toxicity of 4-hydroxynonenal (4-HNE) and related toxic aldehydes. Stable expression of mouse AKR7A5 in V79 cells conferred four-fold increased resistance to 4-HNE cytotoxicity using the MTT assay compared to empty vector-transfected V79 cells. Cells expressing AKR7A5 showed a decrease in mutation rate compared to control cells in the presence of 4-HNE as measured by HGPRT mutagenicity assay. Furthermore, the cells expressing AKR7A5 showed decreased 4-HNE-induced caspase-3 activity in both a time and dose-dependent manner compared to control cells. These results show that in V79 cells 4-HNE mediates apoptosis via caspase-3 activation and that the AKR7A5 enzyme is able to metabolize 4-HNE in cells, thereby attenuating 4-HNE-induced apoptosis. AKR7A isozymes may therefore be important in protecting against toxic aldehydes derived from lipid peroxidation in vivo.
Assuntos
Oxirredutases do Álcool/fisiologia , Aldeídos/toxicidade , Apoptose/efeitos dos fármacos , Inibidores de Cisteína Proteinase/toxicidade , Aldeído Redutase , Aldeídos/antagonistas & inibidores , Aldo-Ceto Redutases , Animais , Western Blotting , Caspase 3 , Caspases/metabolismo , Linhagem Celular , Cricetinae , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Testes de Mutagenicidade , Sais de Tetrazólio , Tiazóis , TransfecçãoRESUMO
The purpose of this study was to test the hypothesis that horses with right dorsal displacement of the large colon (RDDLC) have elevations in serum gamma glutamyl transferase (GGT) activity when compared with horses with left dorsal displacement of the large colon (LDDLC). Medical records from 37 horses with RDDLC and 48 horses with LDDLC were reviewed. Horses were included for study if the RDDLC or LDDLC was confirmed by exploratory laparotomy or postmortem examination and if a serum GGT measurement was obtained within 24 hours before surgery. The proportion of horses with GGT activity within or above the reference range was determined. Of 37 horses, 18 (49%; exact binomial 95% confidence interval, 32-66%) with RDDLC and, of 48 horses, 1 (2%; 95% CI, 0-11%) with LDDLC had GGT above the reference range. Horses with RDDLC had higher serum GGT than did horses with LDDLC. Of 37 horses, 36 (97%) with RDDLC were discharged with a good prognosis and none returned as a result of hepatic disease. Evaluation of surgical and postmortem examinations revealed that positioning of the colon in horses with RDDLC results in compression of the bile duct, which can cause extrahepatic bile duct obstruction and a subsequent elevation in serum GGT activity.