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1.
Int J Obes (Lond) ; 46(1): 100-106, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34508154

RESUMO

BACKGROUND: This study aimed to investigate the influence of body weight, exercise modality, and pace on physiological and perceptual responses to determine the relation between perceptual and physiological responses. METHODS: Aerobically untrained, normal weight, and overweight males and females participated. Participants were randomly assigned to one exercise condition for a 1-mile walk. RESULTS: Prescribed pace resulted in a greater physiological stress than self-selected pace (all p < 0.001) through blood lactate (1.3 ± 0.4 vs 1.7 ± 0.5 mmol), systolic blood pressure (128.9 ± 10.3 vs 139.2 ± 13.2 mmHg), heart rate recovery (2.1 ± 1.7 vs 4.5 ± 2.6 min), oxygen consumption (15.1 ± 2.6 vs 18.1 ± 3.6 ml/kg/min), heart rate (111.7 ± 16.6 vs 134.4 ± 8.3 bpm), and energy expenditure (5.5 ± 1.4 vs 6.8 ± 1.7 kcal/min). Overweight individuals exhibited higher values than normal weight for heart rate (113 ± 8.8 vs 125.5 ± 13.2 bpm, p < 0.001), percentage of max heart rate (60.7 vs 69.0%, p < 0.001), percent of VO2peak (42.2 vs 55.6%, p < 0.001), and total energy expenditure (100.9 ± 27.4 vs 114.1 ± 33.5 kcal, p = 0.022). Greater perceived effort was seen on a treadmill (6.3 ± 0.5 vs 12.5 ± 2.0 RPE, p < 0.001) and at prescribed pace (6.5 ± 1.1 vs 8.9 ± 1.9 RPE, p < 0.001). CONCLUSION: A novel finding of this study was the increased physiological stress and perception of effort on a treadmill and at a prescribed pace, while total energy expenditure showed no significant differences. This could indicate an unfavorable perception and less affective response to the treadmill modality. These results indicate exercise at self-selected pace in preferred environments promotes enjoyable experiences with similar health benefits as those during prescribed higher intensity exercise.


Assuntos
Sobrepeso/psicologia , Velocidade de Caminhada/fisiologia , Caminhada/fisiologia , Caminhada/psicologia , Adulto , Análise de Variância , Teste de Esforço/métodos , Feminino , Humanos , Masculino , Sobrepeso/complicações , Inquéritos e Questionários , Caminhada/estatística & dados numéricos
2.
Philos Trans A Math Phys Eng Sci ; 380(2215): 20210022, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-34865532

RESUMO

Permafrost thaw increases active layer thickness, changes landscape hydrology and influences vegetation species composition. These changes alter belowground microbial and geochemical processes, affecting production, consumption and net emission rates of climate forcing trace gases. Net carbon dioxide (CO2) and methane (CH4) fluxes determine the radiative forcing contribution from these climate-sensitive ecosystems. Permafrost peatlands may be a mosaic of dry frozen hummocks, semi-thawed or perched sphagnum dominated areas, wet permafrost-free sedge dominated sites and open water ponds. We revisited estimates of climate forcing made for 1970 and 2000 for Stordalen Mire in northern Sweden and found the trend of increasing forcing continued into 2014. The Mire continued to transition from dry permafrost to sedge and open water areas, increasing by 100% and 35%, respectively, over the 45-year period, causing the net radiative forcing of Stordalen Mire to shift from negative to positive. This trend is driven by transitioning vegetation community composition, improved estimates of annual CO2 and CH4 exchange and a 22% increase in the IPCC's 100-year global warming potential (GWP_100) value for CH4. These results indicate that discontinuous permafrost ecosystems, while still remaining a net overall sink of C, can become a positive feedback to climate change on decadal timescales. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 2)'.


Assuntos
Pergelissolo , Dióxido de Carbono , Ecossistema , Hidrologia , Metano
3.
Appetite ; 175: 106056, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35447162

RESUMO

In the UK, school food standards have looked to improve the nutritional profile of school food provision and the choices made; however, adolescents' choices tend to bias towards micronutrient poor and energy dense options. This study aimed to explore how adolescents make their school food choices, along with how they engage with their environments whilst selecting food. Seven focus group interviews took place with adolescents (n = 28; 13-14 years) in a secondary school in Northern England. Discussions with participants were audio-recorded, transcribed verbatim and then analysed using an inductive thematic approach. Six themes emerged from the data: (1) parents' and adolescents' roles in the home food environment, (2) burgeoning food autonomy, (3) school food choice factors, (4) social aspects of school food, (5) home versus school, (6) food knowledge & beliefs. Adolescents identified two distinct environments during the focus group discussions: the home and school environments. Adolescents juxtaposed the two, in terms of food provision, food choices, rules and customs surrounding food choice. This juxtaposition emerged as an indirect but important influence on adolescents' school food choices. The school and home environments both (in)directly influence adolescents' school food choices, which involve an integration of multiple, often conflicting influences. Adolescents may adopt a number of unhelpful dietary rationalisations as they try to manage and reconcile these influences. Consultation, together with consideration of relevant food choice models, is required to identify opportunities to influence adolescents' food choices at school.

4.
J Endocrinol Invest ; 44(11): 2417-2426, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33730349

RESUMO

PURPOSE: To determine the utility of estimated glucose disposal rate (eGDR) as a candidate biomarker for thrombotic biomarkers in patients with type 1 diabetes (T1D). METHODS: We reanalysed baseline pretreatment data in a subset of patients with T1D from two previous RCTs, consisting of a panel of thrombotic markers, including fibrinogen, tissue factor (TF) activity, and plasminogen-activator inhibitor (PAI)-1, and TNFα, and clinical factors (age, T1D duration, HbA1c, insulin requirements, BMI, blood pressure, and eGDR). We employed univariate linear regression models to investigate associations between clinical parameters and eGDR with thrombotic biomarkers. RESULTS: Thirty-two patients were included [mean ± SD age 31 ± 7 years, HbA1c of 58 ± 9 mmol/mol (7.5 ± 0.8%), eGDR 7.73 ± 2.61]. eGDR negatively associated with fibrinogen (P < 0.001), PAI-1 concentrations (P = 0.005), and TF activity (P = 0.020), but not TNFα levels (P = 0.881). We identified 2 clusters of patients displaying significantly different characteristics; 56% (n = 18) were categorised as 'higher-risk', eliciting significantly higher fibrinogen (+ 1514 ± 594 µg/mL; P < 0.001), TF activity (+ 59.23 ± 9.42 pmol/mL; P < 0.001), and PAI-1 (+ 8.48 ± 1.58 pmol/dL; P < 0.001), HbA1c concentrations (+ 14.20 ± 1.04 mmol/mol; P < 0.001), age (+ 7 ± 3 years; P < 0.001), duration of diabetes (15 ± 2 years; P < 0.001), BMI (+ 7.66 ± 2.61 kg/m2; P < 0.001), and lower mean eGDR (- 3.98 ± 1.07; P < 0.001). CONCLUSIONS: Compared to BMI and insulin requirements, classical surrogates of insulin resistance, eGDR is a suitable and superior thrombotic risk indicator in T1D. TRIAL REGISTRATION: ISRCTN4081115; registered 27 June 2017.


Assuntos
Glicemia , Diabetes Mellitus Tipo 1 , Fibrinogênio/análise , Hemoglobinas Glicadas , Insulina/uso terapêutico , Inibidor 1 de Ativador de Plasminogênio/sangue , Tromboplastina/análise , Trombose , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Coagulação Sanguínea/fisiologia , Glicemia/análise , Glicemia/metabolismo , Índice de Massa Corporal , Análise por Conglomerados , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Humanos , Resistência à Insulina , Masculino , Agregação Plaquetária/fisiologia , Medição de Risco , Trombose/sangue , Trombose/diagnóstico , Trombose/etiologia
5.
BMC Health Serv Res ; 21(1): 1097, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654429

RESUMO

BACKGROUND: Studies estimate that circumcising men between the ages of 20-30 years who have exhibited previous risky sexual behaviour could reduce overall HIV prevalence. Demand creation strategies for medical male circumcision (MMC) targeting men in this age group may significantly impact these prevalence rates. OBJECTIVES: The objective of this study is to evaluate the cost-effectiveness and cost-benefit of an implementation science, pre-post study designed to increase the uptake of male circumcision for ages 25-49 at a fixed MMC clinic located in Gauteng Province, South Africa. METHODS: A health care provider perspective was utilised to collect all costs. Costs were compared between the standard care scenario of routine outreach strategies and a full intervention strategy. Cost-effectiveness was measured as cost per mature man enrolled and cost per mature man circumcised. A cost-benefit analysis was employed by using the Bernoulli model to estimate the cases of HIV averted due to medical male circumcision (MMC), and subsequently translated to averted medical costs. RESULTS: In the 2015 intervention, the cost of the intervention was $9445 for 722 men. The total HIV treatment costs averted due to the intervention were $542,491 from a public care model and $378,073 from a private care model. The benefit-cost ratio was 57.44 for the public care model and 40.03 for the private care model. The net savings of the intervention were $533,046 or $368,628 - depending on treatment in a public or private setting. CONCLUSIONS: The intervention was cost-effective compared to similar MMC demand interventions and led to statistically significant cost savings per individual enrolled.


Assuntos
Circuncisão Masculina , Infecções por HIV , Adulto , Análise Custo-Benefício , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Comportamento Sexual , África do Sul/epidemiologia , Adulto Jovem
6.
Ann Oncol ; 30(6): 983-989, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31089709

RESUMO

BACKGROUND: Microseminoprotein-beta (MSP), a protein secreted by the prostate epithelium, may have a protective role in the development of prostate cancer. The only previous prospective study found a 2% reduced prostate cancer risk per unit increase in MSP. This work investigates the association of MSP with prostate cancer risk using observational and Mendelian randomization (MR) methods. PATIENTS AND METHODS: A nested case-control study was conducted with the European Prospective Investigation into Cancer and Nutrition (EPIC) with 1871 cases and 1871 matched controls. Conditional logistic regression analysis was used to investigate the association of pre-diagnostic circulating MSP with risk of incident prostate cancer overall and by tumour subtype. EPIC-derived estimates were combined with published data to calculate an MR estimate using two-sample inverse-variance method. RESULTS: Plasma MSP concentrations were inversely associated with prostate cancer risk after adjusting for total prostate-specific antigen concentration [odds ratio (OR) highest versus lowest fourth of MSP = 0.65, 95% confidence interval (CI) 0.51-0.84, Ptrend = 0.001]. No heterogeneity in this association was observed by tumour stage or histological grade. Plasma MSP concentrations were 66% lower in rs10993994 TT compared with CC homozygotes (per allele difference in MSP: 6.09 ng/ml, 95% CI 5.56-6.61, r2=0.42). MR analyses supported a potentially causal protective association of MSP with prostate cancer risk (OR per 1 ng/ml increase in MSP for MR: 0.96, 95% CI 0.95-0.97 versus EPIC observational: 0.98, 95% CI 0.97-0.99). Limitations include lack of complete tumour subtype information and more complete information on the biological function of MSP. CONCLUSIONS: In this large prospective European study and using MR analyses, men with high circulating MSP concentration have a lower risk of prostate cancer. MSP may play a causally protective role in prostate cancer.


Assuntos
Neoplasias da Próstata/sangue , Proteínas Secretadas pela Próstata/sangue , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Seguimentos , Humanos , Masculino , Análise da Randomização Mendeliana/métodos , Pessoa de Meia-Idade , Estado Nutricional , Prognóstico , Estudos Prospectivos , Fatores de Risco
7.
J Antimicrob Chemother ; 74(3): 547-552, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30590583

RESUMO

BACKGROUND: Methicillin resistance in staphylococci is conferred by an alternative PBP (PBP2a/2') with low affinity for most ß-lactam antibiotics. PBP2a is encoded by mecA, which is carried on a mobile genetic element known as SCCmec. A variant of mecA, mecC, was described in 2011 and has been found in Staphylococcus aureus from humans and a wide range of animal species as well as a small number of other staphylococcal species from animals. OBJECTIVES: We characterized a novel mecC allotype, mecC3, encoded by an environmental isolate of Staphylococcus caeli cultured from air sampling of a commercial rabbit holding. METHODS: The S. caeli isolate 82BT was collected in Italy in 2013 and genome sequenced using MiSeq technology. This allowed the assembly and comparative genomic study of the novel SCCmec region encoding mecC3. RESULTS: The study isolate encodes a novel mecA allotype, mecC3, with 92% nucleotide identity to mecC. mecC3 is encoded within a novel SCCmec element distinct from those previously associated with mecC, including a ccrAB pairing (ccrA5B3) not previously linked to mecC. CONCLUSIONS: This is the first description of the novel mecC allotype mecC3, the first isolation of a mecC-positive Staphylococcus in Italy and the first report of mecC in S. caeli. Furthermore, the SCCmec element described here is highly dissimilar to the archetypal SCCmec XI encoding mecC in S. aureus and to elements encoding mecC in other staphylococci. Our report highlights the diversity of mecC allotypes and the diverse staphylococcal species, ecological settings and genomic context in which mecC may be found.


Assuntos
Microbiologia do Ar , Genes Bacterianos , Resistência a Meticilina , Proteínas de Ligação às Penicilinas/genética , Staphylococcus/efeitos dos fármacos , Staphylococcus/genética , Alelos , Animais , Genótipo , Itália , Coelhos , Homologia de Sequência do Ácido Nucleico , Staphylococcus/isolamento & purificação , Sequenciamento Completo do Genoma
8.
Clin Exp Immunol ; 195(2): 277-285, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30303525

RESUMO

Immunosuppression therapies including corticosteroids fail to prevent bronchiolitis obliterans syndrome (BOS), primarily a disease of the small airways, following lung transplantation. We reported increases in steroid-resistant proinflammatory lymphocytes and their loss of histone deacetylase 2 (HDAC2), an important mediator of steroid action, in the blood of stable lung transplant recipients. We noted similar increases in the steroid-resistant lymphocytes in both the blood and small airways in BOS compared with the large airways. We hypothesized that these small airway cells would also exhibit a loss of HDAC2, and that these changes could be reversed by treatment with theophylline (HDAC2 activator). Blood, bronchoalveolar lavage and large and small airway brushings were collected from lung transplant patients with BOS (n = 12) or stable lung function (n = 18) and healthy aged-matched controls (n = 13). Intracellular proinflammatory cytokines [interferon (IFN-γ) and tumour necrosis factor (TNF)-α and HDAC2 were measured in CD8+ T, natural killer (NK) T-like and NK cells from cultured small airway brushings ± 5 mg/l theophylline ± 1 µM prednisolone using flow cytometry. Increased small airway CD8 T, NK T-like and NK cells were identified in BOS versus stable transplant and controls. In BOS, these cells exhibited increased IFN-γ/TNF-α and a loss of HDAC2. HDAC2 expression by small airway CD8+ T cells correlated with forced expiratory volume in 1 s (FEV1 ) (R = 0·880, P = 0·031). Theophylline and prednisolone synergistically up-regulated HDAC2 in CD8+ T cells. BOS is associated with loss of HDAC2 from steroid-resistant proinflammatory CD8+ T, NK T-like and NK cells in the small airways. Therapeutically increasing HDAC2 in these lymphocytes may reduce steroid resistance and improve graft survival.


Assuntos
Broncodilatadores/farmacologia , Linfócitos T CD8-Positivos/metabolismo , Histona Desacetilase 2/metabolismo , Células Matadoras Naturais/metabolismo , Alvéolos Pulmonares/imunologia , Teofilina/farmacologia , Bronquiolite Obliterante/patologia , Bronquiolite Obliterante/prevenção & controle , Linfócitos T CD4-Positivos/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Histona Desacetilase 2/análise , Humanos , Interferon gama/análise , Transplante de Pulmão/efeitos adversos , Pessoa de Meia-Idade , Prednisolona/farmacologia , Fator de Necrose Tumoral alfa/análise
9.
Mol Psychiatry ; 23(5): 1287-1292, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28115737

RESUMO

Cannabis use is observationally associated with an increased risk of schizophrenia, but whether the relationship is causal is not known. Using a genetic approach, we took 10 independent genetic variants previously identified to associate with cannabis use in 32 330 individuals to determine the nature of the association between cannabis use and risk of schizophrenia. Genetic variants were employed as instruments to recapitulate a randomized controlled trial involving two groups (cannabis users vs nonusers) to estimate the causal effect of cannabis use on risk of schizophrenia in 34 241 cases and 45 604 controls from predominantly European descent. Genetically-derived estimates were compared with a meta-analysis of observational studies reporting ever use of cannabis and risk of schizophrenia or related disorders. Based on the genetic approach, use of cannabis was associated with increased risk of schizophrenia (odds ratio (OR) of schizophrenia for users vs nonusers of cannabis: 1.37; 95% confidence interval (CI), 1.09-1.67; P-value=0.007). The corresponding estimate from observational analysis was 1.43 (95% CI, 1.19-1.67; P-value for heterogeneity =0.76). The genetic markers did not show evidence of pleiotropic effects and accounting for tobacco exposure did not alter the association (OR of schizophrenia for users vs nonusers of cannabis, adjusted for ever vs never smoker: 1.41; 95% CI, 1.09-1.83). This adds to the substantial evidence base that has previously identified cannabis use to associate with increased risk of schizophrenia, by suggesting that the relationship is causal. Such robust evidence may inform public health messages about cannabis use, especially regarding its potential mental health consequences.


Assuntos
Fumar Maconha/genética , Esquizofrenia/etiologia , Esquizofrenia/genética , Adulto , Cannabis/metabolismo , Estudos de Casos e Controles , Feminino , Variação Genética , Humanos , Masculino , Abuso de Maconha/genética , Abuso de Maconha/psicologia , Fumar Maconha/efeitos adversos , Fumar Maconha/psicologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Distribuição Aleatória , Fatores de Risco , Fumantes/psicologia , População Branca/genética
10.
Lupus ; 28(8): 1013-1016, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31126212

RESUMO

Livedoid vasculopathy (LV) is a small vessel occlusive disease that can present with a painful purpuric eruption. Predominantly affecting young women, LV has been associated with hypercoagulable states and antiphospholipid syndrome. We present an unusual case of LV occurring in the setting of acute kidney injury secondary to lupus nephritis. It is important to differentiate LV from vasculitis as the treatment recommendation centers on anticoagulation therapy rather than immunosuppression. Additionally, antiphospholipid syndrome should be ruled out in cases of systemic lupus erythematosus with LV due to risk of thrombotic events.


Assuntos
Livedo Reticular/etiologia , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/etiologia , Trombose/etiologia , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica , Feminino , Humanos , Livedo Reticular/patologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Nefrite Lúpica/patologia , Trombose/prevenção & controle , Adulto Jovem
11.
Int J Syst Evol Microbiol ; 69(8): 2208-2213, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31225789

RESUMO

Strain S04009T, a Gram-stain-positive, coagulase-negative staphylococcus, was isolated from bovine mastitis in France. 16S rRNA gene analysis revealed it to be closely related to the coagulase-negative species Staphylococcusxylosus, Staphylococcussaprophyticus, Staphylococcuscaeli and Staphylococcus edaphicus. At the whole-genome level, strain S04009T had an average nucleotide identity value <95 % and an inferred DNA-DNA hybridization value <70 % when compared to these species. Furthermore, phenotypic characteristics distinguished S04009T from those species. From these related species only strain S04009T and S. xylosus are able to ferment xylose and these two can be distinguished by the inability of strain S04009T to express urease activity. Based on the genotypic and phenotypic results, it is proposed that this isolate is a novel species, with the name Staphylococcus pseudoxylosus sp. nov. The type strain is S04009T (=DSM 107950T=CCUG 72763T=NCTC 14184T).


Assuntos
Bovinos/microbiologia , Mastite Bovina/microbiologia , Filogenia , Staphylococcus/classificação , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Feminino , França , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Staphylococcus/isolamento & purificação
12.
Int J Syst Evol Microbiol ; 69(1): 82-86, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30427304

RESUMO

Strain 82T, a Gram-stain-positive, coagulase-negative staphylococcus was isolated from an air sample obtained from an industrial rabbit holding in Italy. It is phylogenetically closely related to the coagulase-negative species Staphylococcus saprophyticus, Staphylococcus xylosus and Staphylococcus edaphicus. However, it could be distinguished from these species by sequence differences between the 16S rRNA, hsp60, rpoB, dnaJ and gap genes. At the whole genome level, the isolate had an average nucleotide identity of <95 % and an inferred DNA-DNA hybridization of <70 % when compared to these species. Based on the genotypic results, it is proposed that this isolate is a novel species, with the name Staphylococcus caeli sp. nov. The type strain is 82BT (=NCTC 14063T=CCUG 71912T).


Assuntos
Microbiologia do Ar , Criação de Animais Domésticos , Filogenia , Staphylococcus/classificação , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Genes Bacterianos , Itália , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética , Coelhos , Análise de Sequência de DNA , Staphylococcus/isolamento & purificação
13.
Adv Gerontol ; 32(3): 422-430, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31512430

RESUMO

We used quantitative real-time PCR method to analyse mtDNA copy number in a random subsample (n=996; 358 men aged 66,31±7,24 years; 468 women aged 67,62±7,1 years) selected from a population cohort (n=9 630) examined at baseline in international project HAPIEE in Novosibirsk, Russia, in 2003-2005. The participants were re-examined after 12 years in 2015-2017. The average relative number of mtDNA copies in peripheral blood leukocytes was greater in women than in men, independently of age and smoking (p=0,001). mtDNA copy number was inversely correlated with age both in men (p=0,005) and women (p<0,001). In age adjusted analysis, mtDNA copy number was inversely associated with waist, hip and heart rate in both sexes. In addition, mtDNA copy number in women was inversely associated with triglycerides and glucose, aterogenity index and positively with HDL cholesterol. In men, mtDNA copy number was positively associated with physical activity. The age-adjusted mean of mtDNA copy number among male never-smokers was greater than in smokers (p=0,003), and the mean mtDNA copy number was lower in women with diabetes than in women without diabetes (p=0,005). In both sexes, subjects with baseline history of hypertension had lower mtDNA copy number after 12-year follow-up than those without hypertension (p=0,05). This broadly supports the hypothesis that mtDNA copy number may act as biomarker of ageing.


Assuntos
Envelhecimento , Biomarcadores , Variações do Número de Cópias de DNA , DNA Mitocondrial , Diagnóstico , Leucócitos , Idoso , Envelhecimento/genética , Biomarcadores/análise , Feminino , Humanos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Federação Russa , Fatores Sexuais
14.
Clin Exp Immunol ; 192(2): 242-250, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29352737

RESUMO

Immunosuppressive therapy fails to suppress the production of proinflammatory cytokines, particularly by CD8+ T cells, in stable lung transplant recipients and those undergoing chronic rejection, suggesting that some patients may become relatively resistant to immunosuppressants such as glucocorticoids (GC). We have shown loss of GC receptor (GCR) from the CD8+ cells, and we hypothesized that the drug membrane efflux pump, p-glycoprotein-1 (Pgp), may also be involved in lymphocyte steroid resistance following lung transplant. Pgp/GCR expression and interferon (IFN)-γ/tumour necrosis factor (TNF)-α proinflammatory cytokine production was measured in blood lymphocytes from 15 stable lung transplant patients, 10 patients with bronchiolitis obliterans syndrome (BOS) and 10 healthy aged-matched controls (± prednisolone ± Pgp inhibitor, cyclosporin A ± GCR activator, Compound A) using flow cytometry. Both Pgp+ and Pgp- lymphocyte subsets from all subjects produced IFN-γ/TNF-α proinflammatory cytokines. Pgp expression was increased in CD8+ Pgp+ T cells and correlated with IFN-γ/TNF-α expression and BOS grade. Reduced GCR was observed in CD8+ Pgp- T, natural killer (NK) T-like and NK cells from stable patients compared with controls, and reduced further in CD8+ Pgp- T cells in BOS. The addition of 2·5 ng/ml cyclosporin A and 1 µM prednisolone inhibit IFN-γ/TNF-α production significantly by CD8+ Pgp+ T cells from BOS patients. The addition of 10 µM Compound A and 1 µM prednisolone inhibit IFN-γ/TNF-α production significantly by CD8+ Pgp- T cells from BOS patients. BOS is associated with increased Pgp expression and loss of GCR from steroid-resistant proinflammatory CD8+ T cells. Treatments that inhibit Pgp and up-regulate GCR in CD8+ T cells may improve graft survival.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Bronquiolite Obliterante/imunologia , Linfócitos T CD8-Positivos/metabolismo , Transplante de Pulmão , Receptores de Glucocorticoides/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Bronquiolite Obliterante/genética , Linfócitos T CD8-Positivos/efeitos dos fármacos , Resistência a Medicamentos , Citometria de Fluxo , Humanos , Interferon gama/sangue , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Pessoa de Meia-Idade , Receptores de Glucocorticoides/genética , Esteroides/administração & dosagem , Fator de Necrose Tumoral alfa/sangue , Membro 4 da Subfamília B de Transportadores de Cassetes de Ligação de ATP
15.
Phys Rev Lett ; 119(7): 075002, 2017 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-28949680

RESUMO

A nonlinear absorber in which the excited state absorption is larger than the ground state can undergo a process called reverse saturable absorption. It is a well-known phenomenon in laser physics in the optical regime, but is more difficult to generate in the x-ray regime, where fast nonradiative core electron transitions typically dominate the population kinetics during light matter interactions. Here, we report the first observation of decreasing x-ray transmission in a solid target pumped by intense x-ray free electron laser pulses. The measurement has been made below the K-absorption edge of aluminum, and the x-ray intensity ranges are 10^{16} -10^{17} W/cm^{2}. It has been confirmed by collisional radiative population kinetic calculations, underscoring the fast spectral modulation of the x-ray pulses and charge states relevant to the absorption and transmission of x-ray photons. The processes shown through detailed simulations are consistent with reverse saturable absorption, which would be the first observation of this phenomena in the x-ray regime. These light matter interactions provide a unique opportunity to investigate optical transport properties in the extreme state of matters, as well as affording the potential to regulate ultrafast x-ray free-electron laser pulses.

16.
Lupus ; 26(8): 857-864, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28121495

RESUMO

Background Belimumab is a monoclonal antibody that reduces B lymphocyte survival by blocking the binding of soluble human B lymphocyte stimulator (BLyS) to its B cell receptors. The utility of belimumab for management of resistant systemic lupus erythematosus (SLE) skin manifestations has not been reported. We present our experience of using this novel molecule for the successful management of cutaneous lupus at our center. Methods We studied five patients with significant SLE skin manifestations. All patients met 1997 American College of Rheumatology (ACR) SLE criteria and had failed multiple medications to control their skin disease. SLE disease activity indexes (SLEDAI), Cutaneous LE disease Area and Severity Index (CLASI) and patient's global assessment (PGA) were recorded before and 16 weeks after belimumab treatment. Belimumab was added to concomitant standard therapy. Results All five patients demonstrated marked clinical improvement subsequent to belimumab treatment. The average time to clinical improvement after treatment initiation was 8-12 weeks. SLEDAI scores (median, range) improved in all the patients ((2, 2-6) to (0, 0-4); p = 0.025). PGA scores (median, range) were better in all patients ((3, 2-3) to (1, 0-1); p = 0.039). CLASI activity scores (median, range) improved dramatically in all patients ((17, 9-31) to (3, 2-14); p = 0.043). There was no worsening of the CLASI damage scores. The mean daily prednisone dose decreased significantly from 31 mg (±18.8) at baseline to 3 mg (± 2.7) ( p = 0.042). Conclusion In this case series, the addition of belimumab to standard therapy improved the signs and symptoms of refractory cutaneous lupus. This is one of the first reports highlighting the potential utility of this medication for the treatment of severe skin involvement in SLE refractory to conventional therapies. Additional studies need to be performed to assess the use of belimumab in the treatment of cutaneous lupus.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Prednisona/administração & dosagem , Adulto , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/administração & dosagem , Humanos , Lúpus Eritematoso Cutâneo/fisiopatologia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
17.
Eur J Cancer Care (Engl) ; 25(2): 262-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26918691

RESUMO

This study aims to examine the survival disparity between Maori men and New Zealand (NZ) Europeans diagnosed with prostate cancer. We identified men aged 40+ years in the Midland Cancer Network region registered with prostate cancer in 2007-2010 in the Cancer Registry. Data were extracted from patient notes of all Maori men and a sample of NZ Europeans. The survival disparity between Maori men and Europeans was estimated by the Kaplan-Meier method and Cox proportional-hazards regression models after adjusting for other factors. This study included 535 men with prostate cancer (135 Maori men and 400 Europeans). The 5-year cancer-specific survival was 98.6% for men diagnosed with localised cancer, 88.8% for locally advanced disease and 19.1% for metastatic cancer. The all-cause survival and the cancer-specific survival were both significantly poorer for Maori men than for NZ Europeans (log rank test: P = 0.004, 0.006 respectively). The hazard ratio of cancer-specific survival for Maori men was 2.01 (95% CI: 1.21-3.36) compared with NZ Europeans. Maori men with prostate cancer had poorer all-cause survival and cancer-specific survival than NZ Europeans. Maori men were at risk of having more advanced disease at diagnosis, which explains most of the survival inequity between Maori men and NZ Europeans.


Assuntos
Disparidades nos Níveis de Saúde , Havaiano Nativo ou Outro Ilhéu do Pacífico , Neoplasias da Próstata/mortalidade , População Branca , Adulto , Idoso , Comorbidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nova Zelândia , Modelos de Riscos Proporcionais , Neoplasias da Próstata/patologia
18.
J Antimicrob Chemother ; 70(6): 1622-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25722301

RESUMO

OBJECTIVES: To characterize the staphylococcal cassette chromosome mec (SCCmec), virulence and antimicrobial susceptibility of Staphylococcus aureus ST130 isolated from mara (Dolichotis patagonum), a large rodent species native to South America and kept in captivity at Copenhagen Zoo. METHODS: The presence of mecC was confirmed by PCR in 15 S. aureus ST130 isolated from mara during a previous study. WGS was performed on two randomly selected isolates to characterize their genomes with respect to SCCmec, virulence and resistance gene content. Antimicrobial susceptibility was tested using commercial broth microdilution tests. RESULTS: All the isolates belonged to spa type t528 ST130 and carried mecC. Based on WGS, mecC was 100% identical to the prototype sequence of S. aureus strain LGA251. The sequence of SCCmec type XI in the mara isolates had 23 SNPs compared with the one described in LGA251. The two sequenced strains harboured a set of virulence factors and other genomic features previously observed in ST130. Both strains carried norA as the only putative antimicrobial resistance gene in addition to mecC. CONCLUSIONS: Our findings support the notion that a genetically conserved mecC-carrying MRSA ST130 clone is widespread in a variety of unrelated hosts in Denmark. Since the mara at Copenhagen Zoo have limited contact with humans and other animal species, it remains unclear whether mara are natural hosts of ST130 or acquired this lineage from unknown sources. The broad host range of MRSA ST130 supports its designation as a generalist lineage.


Assuntos
Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Roedores/microbiologia , Infecções Estafilocócicas/veterinária , Animais , Animais de Zoológico/microbiologia , Antibacterianos/farmacologia , DNA Bacteriano/química , DNA Bacteriano/genética , Dinamarca , Genes Bacterianos , Genoma Bacteriano , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Infecções Estafilocócicas/microbiologia , Fatores de Virulência/genética
19.
Appl Environ Microbiol ; 81(21): 7431-42, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26276115

RESUMO

To gain insight into the mechanisms controlling methanogenic pathways in the Florida Everglades, the distribution and functional activities of methanogens and sulfate-reducing prokaryotes (SRPs) were investigated in soils (0 to 2 or 0 to 4 cm depth) across the well-documented nutrient gradient in the water conservation areas (WCAs) caused by runoff from the adjacent Everglades Agricultural Area. The methyl coenzyme M reductase gene (mcrA) sequences that were retrieved from WCA-2A, an area with relatively high concentrations of SO4 (2-) (≥39 µM), indicated that methanogens inhabiting this area were broadly distributed within the orders Methanomicrobiales, Methanosarcinales, Methanocellales, Methanobacteriales, and Methanomassiliicoccales. In more than 3 years of monitoring, quantitative PCR (qPCR) using newly designed group-specific primers revealed that the hydrogenotrophic Methanomicrobiales were more numerous than the Methanosaetaceae obligatory acetotrophs in SO4 (2-)-rich areas of WCA-2A, while the Methanosaetaceae were dominant over the Methanomicrobiales in WCA-3A (with relatively low SO4 (2-) concentrations; ≤4 µM). qPCR of dsrB sequences also indicated that SRPs are present at greater numbers than methanogens in the WCAs. In an incubation study with WCA-2A soils, addition of MoO4 (2-) (a specific inhibitor of SRP activity) resulted in increased methane production rates, lower apparent fractionation factors [αapp; defined as (amount of δ(13)CO2 + 1,000)/(amount of δ(13)CH4 + 1,000)], and higher Methanosaetaceae mcrA transcript levels compared to those for the controls without MoO4 (2-). These results indicate that SRPs play crucial roles in controlling methanogenic pathways and in shaping the structures of methanogen assemblages as a function of position along the nutrient gradient.


Assuntos
Biota , Metano/metabolismo , Células Procarióticas/classificação , Células Procarióticas/metabolismo , Microbiologia do Solo , Sulfatos/metabolismo , Primers do DNA/genética , Florida , Dados de Sequência Molecular , Oxirredução , Oxirredutases/genética , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/genética , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA
20.
Phys Rev Lett ; 114(1): 015003, 2015 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-25615475

RESUMO

High-intensity x-ray pulses from an x-ray free-electron laser are used to heat and probe a solid-density aluminum sample. The photon-energy-dependent transmission of the heating beam is studied through the use of a photodiode. Saturable absorption is observed, with the resulting transmission differing significantly from the cold case, in good agreement with atomic-kinetics simulations.

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