RESUMO
Glucocorticoids are the standard of care for the treatment of immune-mediated disorders, and ciclosporin is increasingly being used off-label as an adjunct immunosuppressive drug in dogs. However, opportunistic infections can develop during combination immunosuppressive regimens. This case series describes atypical fungal infections in eight dogs treated with immunosuppressive dosages of glucocorticoids and ciclosporin. The median duration of combined treatment prior to the identification of fungal infection was 31 (range, 13 to 201) days, although two dogs received glucocorticoids for prolonged periods prior to the addition of ciclosporin. The estimated prevalence of serious fungal infections with this drug combination appears to be low (approximately 1 · 67%), but these infections led directly or indirectly to death or euthanasia in five of eight (63%) dogs. These cases highlight the need for frequent clinical monitoring of dogs receiving immunosuppressive dosages of glucocorticoids and ciclosporin.
RESUMO
Glutathione-S-transferase enzymes (GSTs) play an important role in the detoxification of environmental carcinogens. Defective GST genotypes are over-represented in human cancers; in particular, low activity GSTT1 genotypes are risk factors for non-Hodgkin lymphoma. We hypothesized that defective GSTT1 genotypes would be associated with lymphoma risk in dogs. To address this, we resequenced the exons, splice junctions, and 3'-UTR of canine GSTT1 in dogs with lymphoma (n = 93) and age-matched unaffected dogs (n = 86). Of 27 canine GSTT1 variants identified, the I2+28 G>A was significantly associated with lymphoma [odds ratio (OR) 6.26, 95% confidence interval (CI), 1.77-22.2], with the AA genotype found in 18.3% of affected dogs but only 3.5% of controls (P = 0.002). This intronic variant was predicted to perturb GSTT1 mRNA splicing, and may increase lymphoma risk by impairing detoxification of environmental chemicals. Confirmation of this finding in a larger population of dogs may support the inclusion of GSTT1 genotyping in epidemiologic studies of canine lymphoma risk.
Assuntos
Doenças do Cão/enzimologia , Regulação Enzimológica da Expressão Gênica , Predisposição Genética para Doença , Glutationa Transferase/metabolismo , Linfoma/veterinária , Polimorfismo Genético , Animais , Estudos de Casos e Controles , Doenças do Cão/genética , Cães , Regulação Neoplásica da Expressão Gênica , Genótipo , Glutationa Transferase/genética , Linfoma/enzimologia , Linfoma/genética , Mutação PuntualRESUMO
BACKGROUND: The diagnosis of intestinal lymphangiectasia (IL) has been associated with characteristic duodenal mucosal changes. However, the sensitivity and specificity of the endoscopic duodenal mucosal appearance for the diagnosis of IL are not reported. HYPOTHESIS/OBJECTIVES: To evaluate the utility of endoscopic images of the duodenum for diagnosis of IL. Endoscopic appearance of the duodenal mucosal might predict histopathologic diagnosis of IL with a high degree of sensitivity and specificity. ANIMALS: 51 dogs that underwent upper gastrointestinal (GI) endoscopy and endoscopic biopsies. METHODS: Retrospective review of images acquired during endoscopy. Dogs were included if adequate biopsies were obtained during upper GI endoscopy and digital images were saved during the procedure. Images were assessed for the presence and severity of IL. Using histopathology as the gold standard, the sensitivity and specificity of endoscopy for diagnosing IL were calculated. RESULTS: Intestinal lymphangiectasia (IL) was diagnosed in 25/51 dogs. Gross endoscopic appearance of the duodenal mucosa had a sensitivity and specificity (95% confidence interval) of 68% (46%, 84%) and 42% (24%, 63%), respectively for diagnosis of IL. Endoscopic images in cases with lymphopenia, hypocholesterolemia, and hypoalbuminemia had a sensitivity of 80%. CONCLUSIONS AND CLINICAL IMPORTANCE: Endoscopic duodenal mucosa appearance alone lacks specificity and has only a moderate sensitivity for diagnosis of IL. Evaluation of biomarkers associated with PLE improved the sensitivity; however, poor specificity for diagnosis of IL supports the need for histopathologic confirmation.
Assuntos
Doenças do Cão/patologia , Duodenopatias/veterinária , Endoscopia do Sistema Digestório/veterinária , Linfangiectasia Intestinal/veterinária , Animais , Biópsia/veterinária , Doenças do Cão/diagnóstico , Cães , Duodenopatias/diagnóstico , Duodenopatias/patologia , Endoscopia do Sistema Digestório/métodos , Endoscopia do Sistema Digestório/normas , Feminino , Linfangiectasia Intestinal/diagnóstico , Linfangiectasia Intestinal/patologia , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade , Estatísticas não ParamétricasRESUMO
We use split ring resonators (SRRs) at optical frequencies to study strong coupling between planar metamaterials and phonon vibrations in nanometer-scale dielectric layers. A series of SRR metamaterials were fabricated on a semiconductor wafer with a thin intervening SiO(2) dielectric layer. The dimensions of the SRRs were varied to tune the fundamental metamaterial resonance across the infrared (IR) active phonon band of SiO(2) at 130 meV (31 THz). Strong anticrossing of these resonances was observed, indicative of strong coupling between metamaterial and phonon excitations. This coupling is very general and can occur with any electrically polarizable resonance including phonon vibrations in other thin film materials and semiconductor band-to-band transitions in the near to far IR. These effects may be exploited to reduce loss and to create unique spectral features that are not possible with metamaterials alone.
RESUMO
Over the last few years, more than 40 partitioning interwell tracer tests (PITTs) have been conducted at many different sites to measure nonaqueous phase liquid (NAPL) saturations in the subsurface. While the main goal of these PITTs was to estimate the NAPL volume in the subsurface, some were specifically conducted to assess the performance of remedial actions involving NAPL removal. In this paper, we present a quantitative approach to assess the performance of remedial actions to recover NAPL that can be used to assess any NAPL removal technology. It combines the use of PITTs (to estimate the NAPL volume in the swept pore volume between injection and extraction wells of a test area) with the use of several cores to determine the vertical NAPL distribution in the subsurface. We illustrate the effectiveness of such an approach by assessing the performance of a surfactant/foam flood conducted at Hill Air Force Base, UT, to remove a TCE-rich NAPL from alluvium with permeability contrasts as high as one order of magnitude. In addition, we compare the NAPL volumes determined by the PITTs with volumes estimated through geostatistical interpolation of aquifer sediment core data collected with a vertical frequency of 5-10 cm and a lateral borehole spacing of 0.15 m. We demonstrate the use of several innovations including the explicit estimation of not only the errors associated with NAPL volumes and saturations derived from PITTs but also the heterogeneity of the aquifer sediments based upon permeability estimates. Most importantly, we demonstrate the reliability of the
Assuntos
Monitoramento Ambiental/métodos , Poluição Ambiental/prevenção & controle , Poluentes do Solo/análise , Poluentes da Água/análise , Sedimentos Geológicos/química , Abastecimento de ÁguaRESUMO
Minority ethnic groups have low income in later life from private pensions, partly due to shorter employment records in Britain since migration. Yet disadvantage and discrimination in the labour market, as well as differences in cultural norms concerning women's employment, may lead to persistence of ethnic variation in private pension acquisition. Little is known about the pension arrangements made by men and women in minority ethnic groups during the working life. This paper examines the extent of ethnic disadvantage in private pension scheme arrangements and analyses variation according to gender and specific ethnic group, using three years of the British Family Resources Survey, which provides information on over 97,000 adults aged 20-59, including over 5,700 from ethnic minorities. Both men and women in minority ethnic groups were less likely to have private pension coverage than their white counterparts but the extent of the difference was most marked for Pakistanis and Bangladeshis. Ethnicity interacted with gender, so that Blacks showed the least gender inequality in private pension arrangements, reflecting the relatively similar full-time employment rates of Black men and women. A minority ethnic disadvantage in private pension coverage, for both men and women, remained after taking account of age, marital and parental status, years of education, employment variables, class and income. The research suggests that minority ethnic groups - especially women - will be disproportionately dependent on means-tested benefits in later life, due to the combined effects of low private pension coverage and the policy of shifting pension provision towards the private sector.
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Etnicidade/estatística & dados numéricos , Grupos Minoritários/estatística & dados numéricos , Pensões/estatística & dados numéricos , Privatização/economia , Adulto , Carência Cultural , Coleta de Dados , Emprego/estatística & dados numéricos , Feminino , Humanos , Renda/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Fatores Socioeconômicos , Reino UnidoRESUMO
Yeast Spt16/Cdc68 and Pob3 form a heterodimer that acts in both DNA replication and transcription. This is supported by studies of new alleles of SPT16 described here. We show that Spt16-Pob3 enhances HO transcription through a mechanism that is affected by chromatin modification, since some of the defects caused by mutations can be suppressed by deleting the histone deacetylase Rpd3. While otherwise conserved among many eukaryotes, Pob3 lacks the HMG1 DNA-binding motif found in similar proteins such as the SSRP1 subunit of human FACT. SPT16 and POB3 display strong genetic interactions with NHP6A/B, which encodes an HMG1 motif, suggesting that these gene products function coordinately in vivo. While Spt16-Pob3 and Nhp6 do not appear to form stable heterotrimers, Nhp6 binds to nucleosomes and these Nhp6-nucleosomes can recruit Spt16-Pob3 to form SPN-nucleosomes. These complexes have altered electrophoretic mobility and a distinct pattern of enhanced sensitivity to DNase I. These results suggest that Spt16-Pob3 and Nhp6 cooperate to function as a novel nucleosome reorganizing factor.
Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas de Grupo de Alta Mobilidade/metabolismo , Proteínas Nucleares/metabolismo , Nucleossomos/fisiologia , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/fisiologia , Fatores de Transcrição , Fatores de Elongação da Transcrição , Alelos , Substituição de Aminoácidos , Antígenos Nucleares , Proteínas de Transporte/genética , Proteínas de Ligação a DNA/genética , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Genótipo , Proteínas HMGN , Proteínas de Grupo de Alta Mobilidade/genética , Histonas/metabolismo , Humanos , Mutagênese Sítio-Dirigida , Proteínas Associadas à Matriz Nuclear , Proteínas Nucleares/genética , Nucleossomos/genética , Fenótipo , Subunidades Proteicas , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/genética , Fuso Acromático , Transcrição GênicaRESUMO
OBJECTIVE: Acute upper gastrointestinal (UGI) hemorrhage is a common, often serious condition encountered in the emergency department (ED). Previous research has suggested that transfusion of blood products may interfere with the hypercoagulable state induced by significant blood loss. Our objective was to determine whether the frequency of rebleeding is higher in patients with UGI bleeding who have received early blood transfusion. METHODS: The study was a retrospective chart review of patients admitted to hospital through the ED with a diagnosis of UGI hemorrhage. Inclusion criteria limited analysis to patients presenting with hematemesis, melena, or bloody nasogastric aspirate, in whom a UGI lesion was confirmed endoscopically during admission. RESULTS: A total of 214 charts were analyzed. Baseline demographic characteristics were similar in transfused and non-transfused patients. Presenting hemoglobin level was lower in the transfused group (86.5 v. 119.2 g/L, p < 0.001). Recurrent bleeding occurred in 99 (46%) patients and was more common in transfused patients (67 [66%] v. 33 [29%], p < 0.001). Logistic regression analysis revealed that transfusion and presenting hemoglobin level were the only variables with a statistically significant independent association with bleeding recurrence (p < 0.001 and p < 0.05 respectively). CONCLUSIONS: Our results support previous research suggesting that transfused UGI bleed patients have a higher rate of rebleeding. However, because of the retrospective design, causality cannot be inferred.
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[formula: see text] The dimethyl(methylthio)sulfonium tetrafluoroborate induced cyclization of various bis(methylsulfanyl) carbonyl compounds is described. The reaction proceeds by methylthiolation of the thioacetal group to give a thionium ion which undergoes subsequent cyclization with the neighboring carbonyl group. This is followed by an elimination reaction to furnish the furan ring.
Assuntos
Acetais/química , Furanos/síntese química , Ciclização , Furanos/químicaAssuntos
Mobilidade Ocupacional , Identidade de Gênero , Renda , Preconceito , Adulto , Feminino , Humanos , Satisfação no Emprego , Masculino , Casamento/psicologia , Pessoa de Meia-Idade , Reino UnidoRESUMO
Little research attention has been given to examining inequalities in the health of elderly women and men, in spite of their high use of health services and the importance of health to maintaining independence in later life. This paper uses data from the British General Household Survey to analyse the variation in health of elderly women and men by class and material circumstances. Two measures of health are used; self-assessed health and functional disability. Elderly women assess their own health less positively than men, and are seriously disadvantaged compared to men in terms of functional disability. Class based on the individual's own previous main occupation is strongly associated with the two measures of health for elderly women and men at all ages. For elderly women, an 'individualistic' approach, using the woman's own last occupation, is compared with the 'conventional' approach of measuring class, which for married women uses their husband's last occupation and for other women their own last occupation. Using the two approaches makes little difference to the strength of association between class and health. Elderly women and men who live in advantaged material circumstances, in terms of income, car ownership and housing tenure, report significantly better health, after controlling for age and class. Level of functional disability is influenced by previous position in the labour market but not current material circumstances. Although elderly women suffer greater morbidity than elderly men, structural inequalities in health are equally pronounced for women and men in later life.