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1.
Artigo em Inglês | MEDLINE | ID: mdl-35401031

RESUMO

Virtual advisors (VAs) are being utilised almost in every service nowadays from entertainment to healthcare. To increase the user's trust in these VAs and encourage the users to follow their advice, they should have the capability of explaining their decisions, particularly, when the decision is vital such as health advice. However, the role of an explainable VA in health behaviour change is understudied. There is evidence that people tend to change their intentions towards health behaviour when the persuasion message is linked to their mental state. Thus, this study explores this link by introducing an explainable VA that provides explanation according to the user's mental state (beliefs and goals) rather than the agent's mental state as commonly utilised in explainable agents. It further explores the influence of different explanation patterns that refer to beliefs, goals, or beliefs&goals on the user's behaviour change. An explainable VA was designed to advise undergraduate students how to manage their study-related stress by motivating them to change certain behaviours. With 91 participants, the VA was evaluated and the results revealed that user-specific explanation could significantly encourage behaviour change intentions and build good user-agent relationship. Small differences were found between the three types of explanation patterns.

2.
Environ Res ; 204(Pt D): 112345, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34774300

RESUMO

Goiter, abnormal enlargement of the thyroid gland, is a significant worldwide public health problem. Iodine deficiency is known as the most common cause. Iodine is actively transported as iodide ion (I-) using Sodium Iodide Symporter (NIS) and sufficient blocking of I- transportation prevents the synthesis of thyroid hormones. The transportation can be blocked by some polyatomic anions known as I- uptake inhibitors. Perchlorate (ClO4-), thiocyanate (SCN-) and nitrate (NO3-) are reported as the major I- uptake inhibitors and exposure could be through various routes. Drinking water is an important exposure route. Since water is essential to sustain life, drinking water safety is very important for the protection of public health. However, as a result of natural and human-based processes, water can be contaminated and contamination of drinking water is a global food safety problem due to causing significant health and environmental problemsIn that context, this study aims to determine exposure levels to I- uptake inhibitors that arise from drinking waters at five different districts in Antalya, Turkey. Collected water samples contained NO3- and ClO4- in the range of 0.86-47.42 mg/L and

Assuntos
Água Potável , Iodo , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Humanos , Iodetos , Pessoa de Meia-Idade , Nitratos/análise , Percloratos , Glândula Tireoide , Adulto Jovem
3.
Am J Lifestyle Med ; 15(3): 313-321, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34025324

RESUMO

Atherosclerosis develops over a long period of time and often begins in childhood. The goal of this study was to make a cross-sectional assessment of the pattern of cardiovascular disease risk factors among Australian vegetarian (n = 49) and nonvegetarian (n = 639) 14- to 17-year-old participants from New South Wales, Australia. Vegetarians had statistically significant lower mean total (4.05 vs 4.4 mmol/L;P < .001) and low-density lipoprotein (LDL) cholesterol (2.18 vs 2.55 mmol/L; P < .001) and lower incidence of abnormal total and LDL cholesterol (31.1% vs 46.2%, P = .036, having total cholesterol ≥4.4 mmol/L and 13.3% vs 29.6%, P = .021, having LDL cholesterol ≥2.84 mmol/L). Vegetarians had a higher diastolic BP (72.0 vs 69.7 mm Hg; P = .038). No statistically significant difference was found in other risk factors including high-density lipoprotein cholesterol (P = .83), triglycerides (P = .601), systolic blood pressure (P = .727), body mass index (P = .159), plasma glucose (P = .09), C-reactive protein (P = .527), or homocysteine (P = .45). The prevalence rate with 3 or more risk factors was 12.2% among vegetarians and 13.9% among nonvegetarians (P = .156). The high percentage of abnormal total cholesterol in both diet groups and, in addition, LDL cholesterol in nonvegetarians is a cause of concern and underlines the need for lifestyle change.

4.
Biomarkers ; 26(2): 114-118, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33284049

RESUMO

INTRODUCTION: Coronavirus disease-2019 (COVID-19) with lung involvement frequently causes morbidity and mortality. Advanced age appears to be the most important risk factor. The receptor for advanced glycation end-product (RAGE) pathway is considered to play important roles in the physiological aging and pathogenesis of lung diseases. This study aimed to investigate the possible relationship between COVID-19 and RAGE pathway. MATERIALS AND METHODS: This study included 23 asymptomatic patients and 35 patients with lung involvement who were diagnosed with COVID-19 as well as 22 healthy volunteers. Lung involvement was determined using computed tomography. Serum soluble-RAGE (sRAGE) levels were determined using enzyme-linked immunosorbent assay. RESULTS: The sRAGE levels were significantly higher in the asymptomatic group than in the control group. Age, fibrinogen, C-reactive protein, and ferritin levels were higher and the sRAGE level was lower in the patients with lung involvement than in the asymptomatic patients. CONCLUSIONS: In this study, patients with high sRAGE levels were younger and had asymptomatic COVID-19. Patients with low sRAGE levels were elderly patients with lung involvement, which indicates that the RAGE pathway plays an important role in the aggravation of COVID-19.


Assuntos
Antígenos de Neoplasias/metabolismo , COVID-19/fisiopatologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transdução de Sinais , Adulto , Idoso , Envelhecimento , COVID-19/complicações , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico por imagem , Pneumonia/etiologia , Tomografia Computadorizada por Raios X
5.
Breast Cancer Res ; 22(1): 113, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109232

RESUMO

BACKGROUND: Immunotherapy has recently been proposed as a promising treatment to stop breast cancer (BrCa) progression and metastasis. However, there has been limited success in the treatment of BrCa with immune checkpoint inhibitors. This implies that BrCa tumors have other mechanisms to escape immune surveillance. While the kynurenine pathway (KP) is known to be a key player mediating tumor immune evasion and while there are several studies on the roles of the KP in cancer, little is known about KP involvement in BrCa. METHODS: To understand how KP is regulated in BrCa, we examined the KP profile in BrCa cell lines and clinical samples (n = 1997) that represent major subtypes of BrCa (luminal, HER2-enriched, and triple-negative (TN)). We carried out qPCR, western blot/immunohistochemistry, and ultra-high pressure liquid chromatography on these samples to quantify the KP enzyme gene, protein, and activity, respectively. RESULTS: We revealed that the KP is highly dysregulated in the HER2-enriched and TN BrCa subtype. Gene, protein expression, and KP metabolomic profiling have shown that the downstream KP enzymes KMO and KYNU are highly upregulated in the HER2-enriched and TN BrCa subtypes, leading to increased production of the potent immunosuppressive metabolites anthranilic acid (AA) and 3-hydroxylanthranilic acid (3HAA). CONCLUSIONS: Our findings suggest that KMO and KYNU inhibitors may represent new promising therapeutic targets for BrCa. We also showed that KP metabolite profiling can be used as an accurate biomarker for BrCa subtyping, as we successfully discriminated TN BrCa from other BrCa subtypes.


Assuntos
Neoplasias da Mama/patologia , Hidrolases/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Quinurenina 3-Mono-Oxigenase/metabolismo , Cinurenina/metabolismo , Redes e Vias Metabólicas , Evasão Tumoral , Adulto , Idoso , Biomarcadores Tumorais/sangue , Neoplasias da Mama/classificação , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Linhagem Celular Tumoral , Estudos de Coortes , Bases de Dados Genéticas , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias
6.
PLoS One ; 13(8): e0201968, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30114226

RESUMO

High protein intake and reduced levels of the essential pyridine nucleotide nicotinamide adenine dinucleotide (NAD+) have both been independently associated with promotion of the ageing phenotype. However, it has not yet been shown whether these two independent observations are biochemically linked. To investigate this possibility, we used a cross-sectional study design of 100 apparently healthy middle-aged males (n = 48) and females, in which we assessed average dietary intakes of multiple components using a validated questionnaire. We also analysed fasting blood levels of urea, NAD+ and its metabolites, and inflammation-linked biomarkers, including interleukin-6 (IL-6), Kynurenine (Kyn), and Tryptophan (Trp). One-way ANOVA and ANCOVA were then performed for statistical analysis. Our results have shown for the first time that plasma levels of NAD+ and Total NAD(H) were lower with increasing protein intake (F (2, 92) = 4.61, P = 0.012; F (2, 92) = 4.55, P = 0.013, respectively). The associated decrease in NAD+ and NAD(H) levels was even stronger with increasing plasma levels of the protein breakdown product urea (F (2, 93) = 25.11, P≤0.001; F (2, 93) = 21.10, P≤0.001). These associations were all independent of age, gender and energy intake. However, no significant association was observed between protein intake or plasma urea, and plasma levels of NAD+ metabolites. We also observed that plasma levels of the inflammatory cytokine IL-6, and both Kyn, and Trp, but not the Kyn/Trp ratio were higher with increasing plasma urea levels (F (2, 94) = 3.30, P = 0.041; F (2, 95) = 7.41, P≤0.001; F (2, 96) = 4.23, P = 0.017, respectively). These associations were dependent on eGFR and energy intake, except for the urea and Trp association that was independent of all. In conclusion, we report for the first time, a novel association between protein intake, its metabolism, and plasma NAD+ levels with a possible link to inflammation. These findings provide further insight into how protein restriction may contribute to the anti-ageing process observed in several studies.


Assuntos
Dieta Rica em Proteínas , NAD/sangue , Adulto , Idoso , Austrália , Biomarcadores , Estudos de Coortes , Feminino , Voluntários Saudáveis , Humanos , Inflamação/sangue , Inflamação/epidemiologia , Mediadores da Inflamação/sangue , Masculino , Metaboloma , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Ureia/sangue
7.
Oxid Med Cell Longev ; 2018: 4504079, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29854082

RESUMO

Lifestyle behaviours have been closely linked to the progressive cell damage associated with oxidative stress (OS) and the development of cardiovascular disease (CVD). Early detection of lifestyle-linked OS may therefore be useful in the early identification of prodromal disease. To test this hypothesis, this study assessed the relationship between a comprehensive redox balance lifestyle score (RBLS) and carotid intima-media thickness (CIMT), a recognized marker for CVD, and plasma biomarkers of OS. In a cross-sectional study design, 100 apparently healthy middle-aged participants were asked to complete a comprehensive lifestyle questionnaire, followed by DXA scanning, CIMT ultrasonography, and blood collection. The RBLS was composed of lifestyle components with pro- and antioxidant properties with a higher score indicative of lower oxidative activity. Multiple linear regression and logistic regression analysis were performed for statistical analysis. The RBLS was significantly associated with the risk for increased CIMT that was independent of conventional CVD risk factors (χ2(9) = 35.60, P ≤ 0.001). The adjusted model explained 42.4% of the variance in CIMT. Participants with RBLS below the median were at significantly increased risk of higher CIMT compared to participants with RBLS above the median (OR = 3.60, 95% CI: 1.19-10.88, P = 0.023). Significant associations were also observed between the RBLS, plasma total antioxidant capacity (TAC) (r(99) = 0.28, P = 0.006), hydroperoxide (HPX) (rs(99) = -0.28, P = 0.005), TAC/HPX ratio (r(98) = 0.41, P ≤ 0.001), γ-glutamyltransferase (r(97) = -0.23, P = 0.024), uric acid (r(98) = -0.20, P = 0.045), and inflammatory C-reactive protein (rs(97) = -0.25, P = 0.012) and interleukin-1ß (r(97) = -0.21, P = 0.040). These findings highlight the importance of identifying the collective influence of lifestyle behaviours on OS activity and its potential to remodel the vascular endothelium.


Assuntos
Espessura Intima-Media Carotídea/instrumentação , Estilo de Vida , Estresse Oxidativo/fisiologia , Humanos , Projetos Piloto , Fatores de Risco
8.
PLoS One ; 12(11): e0187713, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29107974

RESUMO

Oxidative stress has been closely linked to the progressive cell damage associated with emerging non-communicable disease (NCDs). Early detection of these biochemical abnormalities before irreversible cell damage occurs may therefore be useful in identifying disease risk at an individual level. In order to test this hypothesis, this study assessed the relationship between a simple measure of redox status and lifestyle risk factors for NCDs, and the population-based risk score of Framingham. In a cross-sectional study design, 100 apparently healthy middle-aged males (n = 48) and females (n = 52) were asked to complete a comprehensive lifestyle assessment questionnaire, followed by body fat percentage and blood pressure measurements, and blood collection. The ratio of plasma total antioxidant capacity to hydroperoxide (TAC/HPX) was used as an index of redox balance. One-way ANOVA and multiple linear regression analysis were performed to analyse the association between TAC/HPX, lifestyle components and other plasma biomarkers. The TAC/HPX ratio was higher in males compared to females (t96 = 2.34, P = 0.021). TAC/HPX was also lower in participants with poor sleep quality (t93 = 2.39, P = 0.019), with high sleep apnoea risk (t62.2 = 3.32, P = 0.002), with high caffeine (F(2, 93) = 3.97, P = 0.022) and red meat intake (F(2, 93) = 5.55, P = 0.005). These associations were independent of gender. Furthermore, the TAC/HPX ratio decreased with increasing body fat percentage (F(2, 95) = 4.74, P = 0.011) and depression score (t94 = 2.38, P = 0.019), though these associations were dependent on gender. Importantly, a negative association was observed between TAC/HPX levels and the Framingham risk score in both males (r(45) = -0.39, P = 0.008) and females (r(50) = -0.33, P = 0.019) that was independent of other Framingham risk score components. Findings from this study suggests that a relatively simple measure of redox balance such as the TAC/HPX ratio may be a sensitive indicator of redox stress, and may therefore serve as a useful biomarker for assessing an individual's specific NCD risk linked to unhealthy lifestyle practices.


Assuntos
Estilo de Vida , Estresse Oxidativo , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
9.
Lipids Health Dis ; 16(1): 142, 2017 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-28738905

RESUMO

BACKGROUND: Uric acid (UA) has been suggested as a novel risk factor for diabetes. However, its definite role in this prevalent disease is still the subject of much discussion because it is always accompanied with other major risk factors such as obesity and high visceral adiposity. In order to clarify the role of UA in diabetes, this study aimed to investigate the associations between plasma UA and fasting plasma glucose, HbA1c, lipid profile and inflammatory markers after accounting for the contribution of other diabetes risk factors such as BMI and VAT fat mass. METHODS: In the present cross-sectional study, 100 non-diabetic middle-aged males (n = 48) and females (n = 52) were recruited. Central fat distribution measures including android to gynoid fat ratio, VAT and subcutaneous adipose tissue (SAT) fat mass were determined using dual-energy X-ray absorptiometry (DXA). Biochemical analysis was done using methods well established for clinical and research laboratories. Multiple linear regression analysis was performed to analyse the association between plasma UA and the biochemical and central fat distribution measures. RESULTS: UA was positivly associated with body mass index (BMI) (r (98) = 0.42, P ≤ 0.001), android to gynoid fat ratio (r (98) = 0.62, P ≤ 0.001) and VAT fat mass (r (96) = 0.55, P ≤ 0.001). UA was also positively associated with plasma glucose (r (98) = 0.33, P ≤ 0.001), hemoglobin A1c (r (93) = 0.25, P = 0.014), plasma triglyceride (r s (95) = 0.40, P ≤ 0.001), HDL cholesterol (r (98) = - 0.61, P ≤ 0.001) and CRP (r s (98) = 0.23, P = 0.026). However, these associations were no longer significant after accounting for BMI or/and VAT fat mass. No significant association was observed between UA and SAT fat mass (r (97) = 0.02, P ≥ 0.05), Total cholesterol (r (98) = 0.03, P ≥ 0.05), LDL cholesterol (r (98) = 0.13, P ≥ 0.05), TNF-α (r (97) = 0.12, P ≥ 0.05) and IL-6 (r (96) = -0.02, P ≥ 0.05). CONCLUSION: Results from this study suggest, for the first time, that the association between plasma UA and glucose in a non-diabetic population is not direct but rather dependent on VAT fat mass.


Assuntos
Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Gordura Intra-Abdominal/patologia , Ácido Úrico/sangue , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Jejum/sangue , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Gordura Subcutânea/patologia , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangue
10.
Sci Rep ; 7: 41473, 2017 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-28155867

RESUMO

Activation of the kynurenine pathway (KP) of tryptophan metabolism results from chronic inflammation and is known to exacerbate progression of neurodegenerative disease. To gain insights into the links between inflammation, the KP and multiple sclerosis (MS) pathogenesis, we investigated the KP metabolomics profile of MS patients. Most significantly, we found aberrant levels of two key KP metabolites, kynurenic acid (KA) and quinolinic acid (QA). The balance between these metabolites is important as it determines overall excitotoxic activity at the N-methyl-D-Aspartate (NMDA) receptor. We also identified that serum KP metabolic signatures in patients can discriminate clinical MS subtypes with high sensitivity and specificity. A C5.0 Decision Tree classification model discriminated the clinical subtypes of MS with a sensitivity of 91%. After validation in another independent cohort, sensitivity was maintained at 85%. Collectively, our studies suggest that abnormalities in the KP may be associated with the switch from early-mild stage MS to debilitating progressive forms of MS and that analysis of KP metabolites in MS patient serum may have application as MS disease biomarkers.


Assuntos
Progressão da Doença , Cinurenina/metabolismo , Redes e Vias Metabólicas , Metabolômica , Esclerose Múltipla/metabolismo , Adulto , Biomarcadores/metabolismo , Estudos de Coortes , Simulação por Computador , Demografia , Feminino , Seguimentos , Humanos , Imunidade Inata , Masculino , Metaboloma , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/imunologia , Índice de Gravidade de Doença
11.
Anesth Analg ; 123(4): 859-68, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27537929

RESUMO

BACKGROUND: Residual neuromuscular blockade (RNMB) has been linked to adverse respiratory events (AREs) in the postanesthetic care unit (PACU). However, these events are often not attributed to RNMB by anesthesiologists because they may also be precipitated by other factors including obstructive sleep apnea, opioids, or hypnotic agents. Many anesthesiologists believe RNMB occurs infrequently and is rarely associated with adverse outcomes. This study evaluated the prevalence and predictors of RNMB and AREs. METHODS: This prospective cohort study included 599 adult patients undergoing general anesthesia who received neuromuscular blocking agents. Baseline demographic, surgical, and anesthetic variables were collected. RNMB was defined as a train-of-four ratio below 0.90 measured by electromyography on admission to the PACU. AREs were defined based on the modified Murphy's criteria. RESULTS: RNMB was present in 186 patients (31% [95% confidence interval (CI), 27%-35%]) on admission to the PACU. One or more AREs were experienced by 97 patients (16% [95% CI 13-19]). AREs were more frequent in patients with RNMB (21% vs 14%, P = .033). RNMB was significantly associated with age (adjusted relative risk [RR], 1.17 [95% CI, 1.06-1.29] per 10-year increase), type of operation (adjusted RR, 0.59 [95% CI, 0.34-0.99] for laparoscopic surgery compared with open abdominal surgery), and duration of operation (adjusted RR, 0.59 [95% CI, 0.39-0.86] for ≥90 minutes compared with <90 minutes). Using multivariate logistic regression, AREs were found to be independently associated with decreased level of consciousness (adjusted RR, 4.76 [95% CI, 1.49-6.76] for unrousable/unconscious compared with alert/awake) and lower core temperature (adjusted RR, 1.43 [95% CI, 1.04-1.92] per 1°C decrease). Although univariate analysis found a significant association between AREs and RNMB, the significance became borderline after adjusting for other covariates (adjusted RR, 1.46 [95% CI, 0.99-2.08]). CONCLUSIONS: The prevalence of RNMB in the PACU was >30%. Older age, open abdominal surgery, and duration of operation <90 minutes were associated with increased risk of RNMB in our patients. Our RR estimate for AREs was highest for depressed level of consciousness. When AREs occur in the PACU, potentially preventable causes including RNMB, hypothermia, and reduced level of consciousness should be readily identified and treated appropriately. Delaying extubation until the patient is awake and responsive may reduce AREs.


Assuntos
Período de Recuperação da Anestesia , Recuperação Demorada da Anestesia/diagnóstico , Hipotermia/diagnóstico , Bloqueio Neuromuscular/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Transtornos Respiratórios/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Recuperação Demorada da Anestesia/induzido quimicamente , Recuperação Demorada da Anestesia/epidemiologia , Feminino , Humanos , Hipotermia/induzido quimicamente , Hipotermia/epidemiologia , Masculino , Pessoa de Meia-Idade , Bloqueio Neuromuscular/tendências , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/epidemiologia , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Transtornos Respiratórios/induzido quimicamente , Transtornos Respiratórios/epidemiologia , Resultado do Tratamento
12.
J Pharm Biomed Anal ; 120: 190-7, 2016 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-26744989

RESUMO

Goiter is an important health problem all over the world and iodine deficiency is its most common cause. Perchlorate, thiocyanate and nitrate (called as major NIS inhibitors) are known to competitively inhibit iodide uptake by the thyroid gland and thus, human exposure to major NIS inhibitors is a public health concern. In this study, an ion chromatographic method for the determination of most common NIS inhibitor ions in drinking waters was developed and validated. This is the first study where an analytical method is used for the determination of major NIS inhibitors in drinking water by an ion chromatography system in a single run. Chromatographic separations were achieved with an anion-exchange column and separated ions were identified by a conductivity detector. The method was found to be selective, linear, precise accurate and true for all of interested ions. The limits of the detections (LOD) were estimated at 0.003, 0.004 and 0.025mgL(-1) for perchlorate, thiocyanate and nitrate, respectively. Possible interference ions in drinking waters were examined for the best separation of NIS inhibitors. The excellent method validation data and proficiency test result (Z-score for nitrate: -0.1) of the FAPAS(®) suggested that the developed method could be applied for determination of NIS inhibitor residues in drinking waters. To evaluate the usefulness of the method, 75 drinking water samples from Antalya/Turkey were analyzed for NIS inhibitors. Perchlorate concentrations in the samples ranged from not detected (less than LOD) to 0.07±0.02mgL(-1) and the range of nitrate concentrations were found to be 3.60±0.01mgL(-1) and 47.42±0.40mgL(-1). No thiocyanate residues were detected in tested drinking water samples.


Assuntos
Técnicas de Química Analítica/métodos , Água Potável/análise , Simportadores/análise , Poluentes Químicos da Água/análise , Cromatografia por Troca Iônica/métodos , Humanos
13.
Autism Res ; 9(6): 621-31, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26497015

RESUMO

Dysfunction of the serotoninergic and glutamatergic systems is implicated in the pathogenesis of autism spectrum disorder (ASD) together with various neuroinflammatory mediators. As the kynurenine pathway (KP) of tryptophan degradation is activated in neuroinflammatory states, we hypothesized that there may be a link between inflammation in ASD and enhanced KP activation resulting in reduced serotonin synthesis from tryptophan and production of KP metabolites capable of modulating glutamatergic activity. A cross-sectional study of 15 different Omani families with newly diagnosed children with ASD (n = 15) and their age-matched healthy siblings (n = 12) was designed. Immunological profile and the KP metabolic signature were characterized in the study participants. Our data indicated that there were alterations to the KP in ASD. Specifically, increased production of the downstream metabolite, quinolinic acid, which is capable of enhancing glutamatergic neurotransmission was noted. Correlation studies also demonstrated that the presence of inflammation induced KP activation in ASD. Until now, previous studies have failed to establish a link between inflammation, glutamatergic activity, and the KP. Our findings also suggest that increased quinolinic acid may be linked to 16p11.2 mutations leading to abnormal glutamatergic activity associated with ASD pathogenesis and may help rationalize the efficacy of sulforaphane treatment in ASD. Autism Res 2016, 9: 621-631. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.


Assuntos
Transtorno Autístico/imunologia , Transtorno Autístico/metabolismo , Ácido Glutâmico/imunologia , Ácido Glutâmico/metabolismo , Cinurenina/imunologia , Cinurenina/metabolismo , Adolescente , Animais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Omã , Irmãos
14.
Nutr Neurosci ; 18(8): 355-64, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26263423

RESUMO

OBJECTIVE: To evaluate the relationship between folate, cobalamin (Cbl), and homocysteine (Hcy), and markers of inflammation and oxidative stress within the periphery and central nervous system (CNS) of a healthy human cohort. METHODS: Thirty-five matched cerebrospinal fluid (CSF) and plasma samples were collected from consenting participants who required a spinal tap for the administration of anaesthetic. Plasma concentrations of Hcy and both plasma and CSF levels of folate, Cbl, nicotinamide adenine dinucleotide (NAD(H)) and markers of inflammation (interleukin-6, IL-6), and oxidative stress (F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and total antioxidant capacity (TAC)) were quantified. RESULTS: In the peripheral circulation, positive associations were observed between plasma folate and Cbl, and plasma TAC (P ≤ 0.01; P ≤ 0.01) and plasma NAD(H) (P ≤ 0.05; P ≤ 0.05) levels, respectively. Plasma folate was inversely associated with plasma Hcy concentrations (P ≤ 0.05); however, no statistically significant relationships were observed between plasma Hcy and plasma markers of inflammation, oxidative stress, or [NAD(H)]. Within the CNS plasma Hcy correlated positively with CSF IL-6 (P ≤ 0.01) and negatively with CSF NAD(H) (P ≤ 0.05) concentrations. An inverse association was observed between CSF folate and CSF levels of IL-6 (P ≤ 0.05). Unexpectedly, a positive association between CSF Cbl and CSF 8-OHdG levels was also found (P ≤ 0.01). DISCUSSION: These results indicate that folate and Cbl concentrations may influence the levels of oxidative damage, inflammation, and NAD(H), both systemically and within the CNS.


Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Ácido Fólico/administração & dosagem , Inflamação/sangue , NAD/sangue , NAD/líquido cefalorraquidiano , Estresse Oxidativo , Vitamina B 12/administração & dosagem , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Idoso , Antioxidantes/metabolismo , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Sistema Nervoso Central/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Desoxiguanosina/líquido cefalorraquidiano , F2-Isoprostanos/sangue , F2-Isoprostanos/líquido cefalorraquidiano , Feminino , Ácido Fólico/sangue , Ácido Fólico/líquido cefalorraquidiano , Homocisteína/sangue , Homocisteína/líquido cefalorraquidiano , Humanos , Interleucina-6/sangue , Interleucina-6/líquido cefalorraquidiano , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Vitamina B 12/sangue , Vitamina B 12/líquido cefalorraquidiano
15.
Eur J Orthod ; 37(6): 578-83, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25608834

RESUMO

AIM: The purpose of this study was to assess the difference of removal torque values (RTV) and the bone-to-implant contact (BIC) between the sand-blasted, large grit, and acid-etched (SLA) surface-treated and the machined surface (MA) miniscrews. MATERIAL AND METHODS: Miniscrews used in this study were 6mm long with a diameter of 1.5mm. A total of 23 SLA miniscrews and 24 MA miniscrews were placed into the distal femoral condyle of 24 New Zealand rabbits. Removal torque test and the BIC was histologically evaluated at 0 and 8 weeks. RESULTS: There was no statistical difference between the RTV in the MA group versus the SLA group at both 0 and 8 weeks. Comparing 0-8 weeks, there was no significant difference in RTV of the SLA group (P = 0.48), however the change in the MA group was statistically significant (P = 0.006). Histological observation showed a significant decrease in BIC comparing 0 and 8 weeks for the MA group. The BIC ratio at 8 weeks was statistically significantly higher in the SLA group compared to the MA group. CONCLUSION: SLA surface preparation does not increase the RTV of miniscrews. Further investigations under loading and a large sample size are required.


Assuntos
Parafusos Ósseos , Interface Osso-Implante/anatomia & histologia , Procedimentos de Ancoragem Ortodôntica/instrumentação , Desenho de Aparelho Ortodôntico , Condicionamento Ácido do Dente/métodos , Ligas , Animais , Interface Osso-Implante/fisiologia , Ligas Dentárias/química , Corrosão Dentária/métodos , Fêmur/anatomia & histologia , Fêmur/fisiologia , Fêmur/cirurgia , Masculino , Teste de Materiais , Miniaturização , Osseointegração/fisiologia , Coelhos , Propriedades de Superfície , Fatores de Tempo , Titânio/química , Torque
16.
J Neuroinflammation ; 11: 117, 2014 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-24985027

RESUMO

BACKGROUND: The consumption of foods rich in carotenoids that possess significant antioxidant and inflammatory modulating properties has been linked to reduced risk of neuropathology. The objective of this study was to evaluate the relationship between plasma carotenoid concentrations and plasma and cerebrospinal fluid (CSF) markers of inflammation, oxidative stress and nicotinamide adenine dinucleotide (NAD+) in an essentially healthy human cohort. METHODS: Thirty-eight matched CSF and plasma samples were collected from consenting participants who required a spinal tap for the administration of anaesthetic. Plasma concentrations of carotenoids and both plasma and cerebrospinal fluid (CSF) levels of NAD(H) and markers of inflammation (IL-6, TNF-α) and oxidative stress (F2-isoprostanes, 8-OHdG and total antioxidant capacity) were quantified. RESULTS: The average age of participants was 53 years (SD=20, interquartile range=38). Both α-carotene (P=0.01) and ß-carotene (P<0.001) correlated positively with plasma total antioxidant capacity. A positive correlation was observed between α-carotene and CSF TNF-α levels (P=0.02). ß-cryptoxanthin (P=0.04) and lycopene (P=0.02) inversely correlated with CSF and plasma IL-6 respectively. A positive correlation was also observed between lycopene and both plasma (P<0.001) and CSF (P<0.01) [NAD(H)]. Surprisingly no statistically significant associations were found between the most abundant carotenoids, lutein and zeaxanthin and either plasma or CSF markers of oxidative stress. CONCLUSION: Together these findings suggest that consumption of carotenoids may modulate inflammation and enhance antioxidant defences within both the central nervous system (CNS) and systemic circulation. Increased levels of lycopene also appear to moderate decline in the essential pyridine nucleotide [NAD(H)] in both the plasma and the CSF.


Assuntos
Carotenoides/sangue , Carotenoides/líquido cefalorraquidiano , Interleucina-6/líquido cefalorraquidiano , NAD/líquido cefalorraquidiano , Estresse Oxidativo , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Idoso , Antioxidantes/metabolismo , Estudos de Casos e Controles , Cromatografia , Estudos de Coortes , Desoxiguanosina/análogos & derivados , Desoxiguanosina/líquido cefalorraquidiano , F2-Isoprostanos/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Nutr Res ; 34(5): 391-400, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24916552

RESUMO

Research indicates that energy-dense foods increase inflammation and oxidative activity, thereby contributing to the development of vascular disease. However, it is not clear whether the high kilojoule load alone, irrespective of the nutritional content of the ingested food, produces the postprandial oxidative and inflammatory activity. This study investigated the hypothesis that ingestion of a high-fat, high-sugar, phytonutrient-reduced food (ice cream) would increase oxidative and inflammatory activity greater than a kilojoule-equivalent meal of a phytonutrient-rich whole food (avocado). The individual contributions of the fat/protein and sugar components of the ice cream meal to postprandial inflammation and oxidative stress were also quantified. Using a randomized, crossover design, 11 healthy participants ingested 4 test meals: ice cream, avocado, the fat/protein component in ice cream, and the sugar equivalent component in ice cream. Plasma glucose, cholesterol, triglycerides, and inflammatory and oxidative stress markers were measured at baseline and 1, 2, and 4 hours (t1, t2, t4) after ingestion. Lipid peroxidation was increased at 2 hours after eating fat/protein (t0-t2, P < .05) and sugar (t1-t2, P < .05; t1-t4, P < .05). Antioxidant capacity was decreased at 4 hours after eating ice cream (t0-t4, P < .01) and sugar (t0-t4, P < .01). Ingestion of a kilojoule-equivalent avocado meal did not produce any changes in either inflammatory or oxidative stress markers. These data indicate that the ingestion of a phytonutrient-poor food and its individual fat/protein or sugar components increase plasma oxidative activity. This is not observed after ingestion of a kilojoule-equivalent phytonutrient-rich food.


Assuntos
Antioxidantes/administração & dosagem , Dieta , Frutas , Sorvetes , Estresse Oxidativo , Compostos Fitoquímicos/administração & dosagem , Período Pós-Prandial , Adulto , Idoso , Ingestão de Energia , Feminino , Humanos , Peroxidação de Lipídeos , Masculino , Refeições , Pessoa de Meia-Idade , Valor Nutritivo , Persea
18.
Lipids Health Dis ; 12: 79, 2013 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-23710642

RESUMO

BACKGROUND: In recent years the physiological and pathological importance of fatty acids in both the periphery and central nervous system (CNS) has become increasingly apparent. However surprisingly limited research has been conducted comparing the fatty acid composition of central and peripheral lipid stores. METHODS: The present study compared the distribution of polyunsaturated (PUFA), as well as specific saturated (SFA) and monounsaturated (MUFA) fatty acids in the whole blood and cerebrospinal fluid (CSF) of humans. Gas chromatography with flame ionization detection was used to determine the fatty acid profiles of twenty-eight matched CSF and whole blood samples. Multiple linear regression modeling, controlling for age, was used to identify significant relationships. RESULTS: A significant positive relationship was seen between whole blood total omega-3 fatty acids and the CSF omega-3 subfractions, docosapentaenoic acid (DPA) (P = 0.019) and docosahexaenoic acid (DHA) (P = 0.015). A direct association was also observed between the whole blood and CSF omega-6 PUFA, arachidonic acid (AA) (P = 0.045). Interestingly an inverse association between central and peripheral oleic acid was also found (P = 0.045). CONCLUSIONS: These findings indicate a relationship between central and peripheral fatty acids of varying degrees of unsaturation and chain length and support the view that some systemic fatty acids are likely to cross the human blood brain barrier (BBB) and thereby influence central fatty acid concentrations.


Assuntos
Sistema Nervoso Central/metabolismo , Ácidos Graxos Ômega-3/sangue , Sistema Nervoso Periférico/metabolismo , Adulto , Ácidos Graxos/sangue , Ácidos Graxos/líquido cefalorraquidiano , Ácidos Graxos/classificação , Ácidos Graxos Monoinsaturados/sangue , Ácidos Graxos Monoinsaturados/líquido cefalorraquidiano , Ácidos Graxos Monoinsaturados/classificação , Ácidos Graxos Ômega-3/líquido cefalorraquidiano , Ácidos Graxos Ômega-3/classificação , Ácidos Graxos Insaturados/sangue , Ácidos Graxos Insaturados/líquido cefalorraquidiano , Ácidos Graxos Insaturados/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Transfusion ; 52(5): 1079-85, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21980987

RESUMO

BACKGROUND: Cord blood (CB) is a product rich in primitive adult stem cells used in hematopoietic stem cell transplantation. After collection, the CB is transported to a facility where the unit is processed and then frozen up to 48 hours later. These processes can lead to compromised white blood cell (WBC) viability. This study investigates the factors that affect WBC viability before freezing of the cells. STUDY DESIGN AND METHODS: We retrospectively analyzed WBC viability from 9918 CB collections harvested from 2003 to 2010 to determine if collection volume and time to freezing (TTF) had a significant effect on WBC viability. CB was collected in dispersed clinical locations by local staff trained to the same methods. CB was transported to the central lab under controlled conditions for analysis and processing. RESULTS: The collected CB units had a mean volume of 77.1 ± 31.3 mL, mean WBC count of 10.5 × 10(8) ± 5.6 × 10(8) , mean total CD34+ cell count of 4.0 × 10(6) ± 3.7 × 10(6) , and mean WBC viability of 91.7% ± 6.5%. WBC viability was most significantly affected by the volume of CB collected and the TTF. As collection volumes increased, WBC viability increased, with mean viability of 95.0% ± 3.5% in CB collections of more than 120 mL. Decreased viability was associated with volumes of less than 60 mL and TTF of more than 24 hours. From these data we have developed decision tables that estimate WBC viability based on CB volume and TTF. CONCLUSION: This study identifies optimal TTF for different collection volumes to maintain WBC viability of the collected CB.


Assuntos
Coleta de Amostras Sanguíneas , Sangue Fetal , Leucócitos/fisiologia , Volume Sanguíneo , Sobrevivência Celular , Feminino , Congelamento , Humanos , Contagem de Leucócitos , Gravidez , Estudos Retrospectivos
20.
Asia Pac J Clin Nutr ; 19(4): 526-33, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21147714

RESUMO

In Western countries the increasing prevalence of obesity in young people is a major public health concern. While the focus has been on reducing obesity, paradoxically the success of these campaigns may result in unhealthy nutritional practices. The aim of this study was to investigate the use and impact of weight control techniques on the health of adolescent females. Using Analysis of Variance we compared physiological and biochemical markers of health against responses to a modified, Schools Physical Activity and Nutrition Survey (SPANS) in 482 adolescent females (14-17 yrs) from secondary schools in the northern Sydney and Central Coast regions of New South Wales, Australia. Participants who 'often' used weight control methods had, on average, a healthy BMI of 22.5 (SD=3.7). However, comparison of blood derived markers between participants who 'never', 'occasionally' or 'often' used weight reduction techniques showed that, those who 'often' used weight control methods had significantly lower haemoglobin (p<0.05), alkaline phosphatase (p<0.001), bilirubin (p<0.05), albumin (p<0.05), total protein (p<0.05), and calcium (p<0.05), but higher blood levels of creatinine (p<0.05) and potassium (p<0.05). These data suggest that the use of common weight control techniques by healthy weight adolescent females can produce a metabolically divergent group whose biochemical markers are consistent with subtle levels of chronic under-nutrition.


Assuntos
Dieta Redutora/efeitos adversos , Dieta Redutora/métodos , Desnutrição/epidemiologia , Adolescente , Fenômenos Fisiológicos da Nutrição do Adolescente , Albuminas , Fosfatase Alcalina/sangue , Análise de Variância , Austrália/epidemiologia , Bilirrubina/sangue , Biomarcadores/sangue , Proteínas Sanguíneas , Cálcio/sangue , Causalidade , Estudos de Coortes , Creatinina/sangue , Feminino , Hemoglobinas , Humanos , Desnutrição/sangue , Inquéritos Nutricionais/métodos , Inquéritos Nutricionais/estatística & dados numéricos , Potássio/sangue
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