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1.
Rev Med Suisse ; 15(662): 1625-1628, 2019 Sep 11.
Artigo em Francês | MEDLINE | ID: mdl-31508914

RESUMO

The salt sensitivity of the blood pressure (SSBP) is defined as a rise or fall in blood pressure induced by a change in sodium intake. There is an interindividual variation and no strong diagnostic criteria exist to date. The SSBP may lead to underestimation of the beneficial effect of sodium restriction in some patients in meta-analyzes. High sodium intake in salt sensitive patients results in an increase in the prevalence of hypertension and target organ damage. The etiology seems to be a failure of one or more natriuretic mechanisms. Some environmental, genetic and epidemiological factors increase its susceptibility. Per se, SSBP cannot be treated, but its identification may help in preventing hypertension and adapt the treatment in some populations.


Assuntos
Variação Biológica Individual , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Cloreto de Sódio na Dieta/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Humanos , Hipertensão/diagnóstico
2.
Artigo em Inglês | MEDLINE | ID: mdl-31527390

RESUMO

An overwhelming amount of evidence now suggests that some people are becoming overloaded with neurotoxins. This is mainly from changes in their living environment and style, coupled with the fact that all people are different and display a broad distribution of genetic susceptibilities. It is important for individuals to know where they lie concerning their ability to either reject or retain toxins. Everyone is contaminated with a certain baseline of toxins that are alien to the body, namely aluminum, arsenic, lead, and mercury. Major societal changes have modified their intake, such as vaccines in enhanced inoculation procedures and the addition of sushi into diets, coupled with the ever-present lead, arsenic, and traces of manganese. It is now apparent that no single toxin is responsible for the current neurological epidemics, but rather a collaborative interaction with possible synergistic components. Selenium, although also a neurotoxin if in an excessive amount, is always present and is generally more present than other toxins. It performs as the body's natural chelator. However, it is possible that the formation rates of active selenium proteins may become overburdened by other toxins. Every person is different and it now appears imperative that the medical profession establish an individual's neurotoxicity baseline. Moreover, young women should certainly establish their baselines long before pregnancy in order to identify possible risk factors.


Assuntos
Arsênico/sangue , Poluentes Ambientais/sangue , Metais Pesados/sangue , Síndromes Neurotóxicas , Selênio/sangue , Variação Biológica Individual , Biomarcadores/sangue , Humanos
3.
Kidney Blood Press Res ; 44(4): 727-742, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31387100

RESUMO

BACKGROUND: Studies have demonstrated that cholesterol variability is an independent predictor of cerebrovascular and cardiovascular events. OBJECTIVE: This study aimed to investigate the association of visit-to-visit variability in total cholesterol (TC) with kidney decline in a Chinese community-based population. METHODS: We assessed intraindividual variability in TC among 6,465 hypertensive participants and correlated the results with endpoints. TC variability was measured using standard deviation (SD), average successive variability (ASV), coefficient of variation (CV), and variability independent of the mean (VIM). The endpoint of this study was progression of renal function decline defined as a decrease in estimated glomerular filtration rate (eGFR) ≥30% and to a level <60 mL/min/1.73 m2 during follow-up if the baseline eGFR was ≥60 mL/min/1.73 m2, or a decrease in eGFR ≥50% during follow up if the baseline eGFR was <60 mL/min/1.73 m2. RESULTS: After a median follow-up of 27 months, 13.5% (n = 877) of the participants experienced progression of renal function decline. In the multivariable-adjusted Cox model, each 1-SD increase in TC variability (by SD) increased the risk of renal function decline by 11% (HR = 1.11; 95% CI 1.034-1.197; p = 0.004); this was independent of the baseline eGFR, mean follow-up TC levels, and the lipid-lowering therapy. Similar results were found for the 3 other measures of variability, i.e., ASV, CV, and VIM. CONCLUSION: In subjects with hypertension, visit-to-visit variability in TC is an independent predictor of renal function decline.


Assuntos
Variação Biológica Individual , Colesterol/sangue , Progressão da Doença , Hipertensão , Insuficiência Renal Crônica/diagnóstico , Idoso , Grupo com Ancestrais do Continente Asiático , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Saúde Pública , Insuficiência Renal Crônica/fisiopatologia , Reprodutibilidade dos Testes
4.
Nutrients ; 11(8)2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31387247

RESUMO

Plant-based diets rich in bioactive compounds such as polyphenols have been shown to positively modulate the risk of cardiometabolic (CM) diseases. The inter-individual variability in the response to these bioactives may affect the findings. This systematic review aimed to summarize findings from existing randomized clinical trials (RCTs) evaluating the effect of hydroxycinnamic acids (HCAs) on markers of CM health in humans. Literature searches were performed in PubMed and the Web of Science. RCTs on acute and chronic supplementation of HCA-rich foods/extracts on CM biomarkers were included. Forty-four RCTs (21 acute and 23 chronic) met inclusion criteria. Comparisons were made between RCTs, including assessments based on population health status. Of the 44 RCTs, only seven performed analyses on a factor exploring inter-individual response to HCA consumption. Results demonstrated that health status is a potentially important effect modifier as RCTs with higher baseline cholesterol, blood pressure and glycaemia demonstrated greater overall effectiveness, which was also found in studies where specific subgroup analyses were performed. Thus, the effect of HCAs on CM risk factors may be greater in individuals at higher CM risk, although future studies in these populations are needed, including those on other potential determinants of inter-individual variability. PROSPERO, registration number CRD42016050790.


Assuntos
Variação Biológica Individual , Doenças Cardiovasculares/prevenção & controle , Ácidos Cumáricos/administração & dosagem , Dieta , Suplementos Nutricionais , Doenças Metabólicas/prevenção & controle , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Ácidos Cumáricos/efeitos adversos , Dieta/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Feminino , Humanos , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/fisiopatologia , Pessoa de Meia-Idade , Estado Nutricional , Valor Nutritivo , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Comportamento de Redução do Risco , Adulto Jovem
5.
Psicothema (Oviedo) ; 31(3): 229-238, ago. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-185348

RESUMO

Background: Are cognitive and biological variables useful for predicting future behavioral outcomes?. Method: In two independent groups, we measured a set of cognitive (fluid and crystallized intelligence, working memory, and attention control) and biological (cortical thickness and cortical surface area) variables on two occasions separated by six months, to predict behavioral outcomes of interest (performance on an adaptive version of the n-back task) measured twelve and eighteen months later. We followed three stages: discovery, validation, and generalization. In the discovery stage, cognitive/biological variables and the behavioral outcome of interest were assessed in a group of individuals (in-sample). In the validation stage, the cognitive and biological variables were related with a parallel version of the behavioral outcome assessed several months later. In the generalization stage, the validation findings were tested in an independent group of individuals (out-of-sample). Results: The key finding revealed that cortical surface area variations within the right dorsolateral prefrontal cortex predict the behavioral outcome of interest in both groups, whereas the cognitive variables failed to show reliable predictive validity. Conclusions: Individual differences in biological variables might predict future behavioral outcomes better than cognitive variables concurrently correlated with these behavioral outcomes


Antecedentes: ¿Predicen las variables cognitivas y biológicas el futuro desempeño cognitivo? Método: en dos grupos independientes de participantes se miden variables cognitivas (inteligencia fluida y cristalizada, memoria operativa y control atencional) y biológicas (grosor y superficie cortical) en dos ocasiones separadas por seis meses, para predecir el desempeño en la tarea n-back valorado doce y dieciocho meses después. Se completan tres etapas: descubrimiento, validación y generalización. En la de descubrimiento se valoran en un grupo de individuos las variables cognitivas/biológicas y el desempeño a predecir. En la de validación, se relacionan las mismas variables con una versión paralela de la n-back completada meses después. En la de generalización, los resultados de la validación se replican en un grupo independiente de individuos. Resultados: las variaciones de superficie cortical en la corteza dorsolateral prefrontal derecha predicen el desempeño cognitivo en los dos grupos independientes de individuos, mientras que las variables cognitivas no contribuyen a la predicción del desempeño futuro. Conclusiones: las diferencias individuales en determinadas variables biológicas predicen el desempeño cognitivo mejor que las variables cognitivas que correlacionan concurrentemente con ese desempeño


Assuntos
Humanos , Feminino , Atenção/fisiologia , Comportamento , Cognição/fisiologia , Inteligência/fisiologia , Memória de Curto Prazo/fisiologia , Córtex Pré-Frontal/anatomia & histologia , Variação Biológica Individual , Mapeamento Encefálico , Estudos Controlados Antes e Depois/métodos , Lateralidade Funcional , Generalização (Psicologia) , Imagem por Ressonância Magnética , Córtex Pré-Frontal/diagnóstico por imagem , Testes Psicológicos , Reprodutibilidade dos Testes , Fatores de Tempo
7.
Psicothema ; 31(3): 229-238, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31292036

RESUMO

BACKGROUND: Are cognitive and biological variables useful for predicting future behavioral outcomes? METHOD: In two independent groups, we measured a set of cognitive (fluid and crystallized intelligence, working memory, and attention control) and biological (cortical thickness and cortical surface area) variables on two occasions separated by six months, to predict behavioral outcomes of interest (performance on an adaptive version of the n-back task) measured twelve and eighteen months later. We followed three stages: discovery, validation, and generalization. In the discovery stage, cognitive/biological variables and the behavioral outcome of interest were assessed in a group of individuals (in-sample). In the validation stage, the cognitive and biological variables were related with a parallel version of the behavioral outcome assessed several months later. In the generalization stage, the validation findings were tested in an independent group of individuals (out-of-sample). RESULTS: The key finding revealed that cortical surface area variations within the right dorsolateral prefrontal cortex predict the behavioral outcome of interest in both groups, whereas the cognitive variables failed to show reliable predictive validity. CONCLUSIONS: Individual differences in biological variables might predict future behavioral outcomes better than cognitive variables concurrently correlated with these behavioral outcomes.


Assuntos
Atenção/fisiologia , Comportamento , Cognição/fisiologia , Inteligência/fisiologia , Memória de Curto Prazo/fisiologia , Córtex Pré-Frontal/anatomia & histologia , Variação Biológica Individual , Mapeamento Encefálico , Estudos Controlados Antes e Depois/métodos , Feminino , Previsões , Lateralidade Funcional , Humanos , Imagem por Ressonância Magnética , Córtex Pré-Frontal/diagnóstico por imagem , Testes Psicológicos , Reprodutibilidade dos Testes , Fatores de Tempo
8.
Genes (Basel) ; 10(7)2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31311141

RESUMO

Over the last years, a growing body of evidence suggests that gut microbial communities play a fundamental role in many aspects of human health and diseases. The gut microbiota is a very dynamic entity influenced by environment and nutritional behaviors. Considering the influence of such a microbial community on human health and its multiple mechanisms of action as the production of bioactive compounds, pathogens protection, energy homeostasis, nutrients metabolism and regulation of immunity, establishing the influences of different nutritional approach is of pivotal importance. The very low carbohydrate ketogenic diet is a very popular dietary approach used for different aims: from weight loss to neurological diseases. The aim of this review is to dissect the complex interactions between ketogenic diet and gut microbiota and how this large network may influence human health.


Assuntos
Dieta Cetogênica , Microbiota , Animais , Variação Biológica Individual , Metabolismo dos Carboidratos , Microbioma Gastrointestinal , Humanos , Cetose
9.
Neuropsychology ; 33(5): 642-657, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31246073

RESUMO

OBJECTIVE: Mean speed of responding is the most commonly used measure in the assessment of reaction time (RT). An alternative measure is intraindividual variability (IIV): the inconsistency of responding across multiple trials of a test. IIV has been suggested as an important indicator of central nervous system functioning, and as such, there has been increasing interest in the associations between IIV and brain imaging metrics. Results however, have been inconsistent. The present seeks to provide a comprehensive evaluation of the associations between a variety of measures of brain white matter integrity and individual differences in choice RT (CRT) IIV. METHOD: MRI brain scans of members of the Lothian Birth Cohort 1936 were assessed to obtain measures of the volume and severity of white matter hyperintensities, and the integrity of brain white matter tracts. CRT was assessed with a 4 CRT task on a separate occasion. Data were analyzed using multiple regression (N range = 358-670). RESULTS: Greater volume of hyperintensities and more severe hyperintensities in frontal regions were associated with higher CRT IIV. White matter tract integrity, as assessed by both fractional anisotropy and mean diffusivity, showed the smallest effect sizes in associations with CRT IIV. Associations with hyperintensities were attenuated and no longer significant after controlling for M CRT. CONCLUSIONS: Taken together, the results of the present study suggested that IIV was not incrementally predictive of white matter integrity over mean speed. This is in contrast to previous reports, and highlights the need for further study. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Envelhecimento/patologia , Envelhecimento/fisiologia , Variação Biológica Individual , Lobo Frontal/patologia , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Substância Branca/patologia , Idoso , Envelhecimento Cognitivo/fisiologia , Estudos de Coortes , Imagem de Difusão por Ressonância Magnética , Feminino , Lobo Frontal/diagnóstico por imagem , Humanos , Masculino , Substância Branca/diagnóstico por imagem
10.
Drugs R D ; 19(2): 201-212, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31073875

RESUMO

BACKGROUND AND OBJECTIVE: Given that a high intrapatient variability (IPV) of tacrolimus whole blood concentration increases the risk for a poor kidney transplant outcome, some experts advocate routine IPV monitoring for detection of high-risk patients. However, attempts to estimate the variance of tacrolimus trough concentrations (TTC) are limited by the need for patients to receive a fixed dose over time and/or the use of linear statistical models. A goal of this study is to overcome the current limitations through the novel application of statistical methodology generalizing the relationship between TTC and dose through the use of nonparametric functional regression modeling. METHODS: With TTC as a response and dose as a covariate, the model employs an unknown bivariate function, allowing for the potentially complex, nonlinear relationship between the two parameters. A dose-adjusted variance of TTC is then derived based on standard functional principal component analysis (FPCA). To assess the model, it was compared against an FPCA-based model and linear mixed-effects models using prediction error, bias, and coverage probabilities for simulated data as well as phase III data from the Astellas new drug application studies for extended-release tacrolimus. RESULTS: Our numerical investigation indicates that the new model better predicts dose-adjusted TTCs compared with the prediction of linear mixed effects models. Estimated coverage probabilities also indicate that the new model accurately accounts for the variance of TTC during the periods of large fluctuation in dose, whereas the linear mixed effects model consistently underestimates the coverage probabilities because of the inaccurate characterization of TTC fluctuation. CONCLUSION: This is the first known application of a functional regression model to assess complex relationships between TTC and dose in a real clinical setting. This new method has applicability in future clinical trials including real-world data sets due to flexibility of the nonparametric modeling approach.


Assuntos
Monitoramento de Medicamentos/métodos , Imunossupressores/farmacocinética , Modelos Biológicos , Tacrolimo/farmacocinética , Área Sob a Curva , Variação Biológica Individual , Ensaios Clínicos Fase III como Assunto , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Relação Dose-Resposta a Droga , Estudos de Viabilidade , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Tacrolimo/administração & dosagem
11.
PLoS One ; 14(5): e0216209, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31120896

RESUMO

BACKGROUND: Preoperative cognitive reserve and brain integrity may explain commonly observed intraoperative fluctuations seen on a standard anesthesia depth monitor used ubiquitously in operating rooms throughout the nation. Neurophysiological variability indicates compromised regulation and organization of neural networks. Based on theories of neuronal integrity changes that accompany aging, we assessed the relative contribution of: 1) premorbid cognitive reserve, 2) current brain integrity (gray and white matter markers of neurodegenerative disease), and 3) current cognition (specifically domains of processing speed/working memory, episodic memory, and motor function) on intraoperative neurophysiological variability as measured from a common intraoperative tool, the Bispectral Index Monitor (BIS). METHODS: This sub-study included participants from a parent study of non-demented older adults electing unilateral Total Knee Arthroplasty (TKA) with the same surgeon and anesthesia protocol, who also completed a preoperative neuropsychological assessment and preoperative 3T brain magnetic resonance imaging scan. Left frontal two-channel derived EEG via the BIS was acquired preoperatively (un-medicated and awake) and continuously intraoperatively with time from tourniquet up to tourniquet down. Data analyses used correlation and regression modeling. RESULTS: Fifty-four participants met inclusion criteria for the sub-study. The mean (SD) age was 69.5 (7.4) years, 54% were male, 89% were white, and the mean (SD) American Society of Anesthesiologists score was 2.76 (0.47). We confirmed that brain integrity positively and significantly associated with each of the cognitive domains of interest. EEG intra-individual variability (squared deviation from the mean BIS value between tourniquet up and down) was significantly correlated with cognitive reserve (r = -.40, p = .003), brain integrity (r = -.37, p = .007), and a domain of processing speed/working memory (termed cognitive efficiency; r = -.31, p = .021). Hierarchical regression models that sequentially included age, propofol bolus dose, cognitive reserve, brain integrity, and cognitive efficiency found that intraoperative propofol bolus dose (p = .001), premorbid cognitive reserve (p = .008), and current brain integrity (p = .004) explained a significant portion of intraoperative intra-individual variability from the BIS monitor. CONCLUSIONS: Older adults with higher premorbid reserve and less brain disease were more stable intraoperatively on a depth of anesthesia monitor. Researchers need to replicate findings within larger cohorts and other surgery types.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Reserva Cognitiva/efeitos dos fármacos , Reserva Cognitiva/fisiologia , Idoso , Anestesia Geral/métodos , Variação Biológica Individual , Biomarcadores/metabolismo , Encéfalo/metabolismo , Monitores de Consciência , Eletroencefalografia/métodos , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/fisiopatologia , Testes Neuropsicológicos , Período Pré-Operatório , Propofol/administração & dosagem
12.
Eur J Clin Pharmacol ; 75(8): 1069-1075, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31139866

RESUMO

BACKGROUND: Routine laboratory monitoring of rivaroxaban and dose adjustment relating to exposure is currently not recommended. However, in certain clinical situations, assessment of rivaroxaban levels is desirable. OBJECTIVES: To examine inter- and intra-subject plasma rivaroxaban variability in patients with atrial fibrillation (AF) and to correlate these results to clinical outcomes. PATIENTS/METHODS: We included 60 patients with AF treated with rivaroxaban: half on 20 mg daily (R20) and half on 15 mg daily (R15). Three trough and peak blood samples were collected with an interval of 6-8 weeks apart. Plasma rivaroxaban concentration was measured directly by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) and indirectly by anti-Xa for rivaroxaban, prothrombin time (PT), and activated partial thromboplastin time (APTT). RESULTS: Patients on R15 were older (76 ± 6 vs 71 ± 6 years), had lower creatinine clearance (60 ± 26 vs 99 ± 32 mL/min), higher CHADS2 (2.5 ± 1.2 vs 1.8 ± 1.3), all p < 0.01, but had similar rivaroxaban concentrations in trough samples to patients on R20. There was no significant intra-individual variability for trough or peak rivaroxaban concentration assessed by LC-MS/MS, anti-Xa, or PT. Trough rivaroxaban levels determined by LC-MS/MS (48 ± 30 vs 34 ± 26, p = 0.02) and anti-Xa, but not with PT and APTT, were higher in patients with bleeding than in patients without it. CONCLUSIONS: There is a pronounced inter-, but not intra-individual variability in the rivaroxaban trough levels in patients with AF. Assessment of trough rivaroxaban concentration with LC-MS/MS or anti-Xa, but not with APTT or PT, may help to identify patients at increased risk of bleeding.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Variação Biológica Individual , Variação Biológica da População , Inibidores do Fator Xa/farmacologia , Hemorragia/epidemiologia , Rivaroxabana/farmacologia , Idoso , Idoso de 80 Anos ou mais , Testes de Coagulação Sanguínea/estatística & dados numéricos , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/estatística & dados numéricos , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Medição de Risco , Rivaroxabana/uso terapêutico
13.
Arch Soc Esp Oftalmol ; 94(7): 337-342, 2019 Jul.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31122680

RESUMO

OBJECTIVE: Because of high variability, tear film osmolarity measures have been questioned in dry eye assessment. Understanding the origin of such variability would aid data interpretation. This study aims to evaluate osmolarity variability in a clinical setting. MATERIAL AND METHODS: Twenty dry eyes and 20 control patients were evaluated. Three consecutive osmolarity measurements per eye at 5min intervals were obtained. Variability was represented by the difference between both extreme readings per eye. Machine learning techniques were used to quantify discrimination capacity of tear osmolarity for dry eye. RESULTS: Mean osmolarities in the control and dry eye groups were 295.1±7.3mOsm/L and 300.6±11.2mOsm/L, respectively (P=.004). Osmolarity variabilities were 7.5±3.6mOsm/L and 16.7±11.9mOsm/L, for the control and dry eye groups, respectively (P<.001). Based on osmolarity, a logistic classifier showed an 85% classification accuracy. CONCLUSIONS: In the clinical setting, both mean osmolarity and osmolarity variability in the dry eye group were significantly higher than in the control group. Machine learning techniques showed good classification accuracy. It is concluded that higher variability of tear osmolarity is a dry eye feature.


Assuntos
Síndromes do Olho Seco/diagnóstico , Aprendizado de Máquina , Lágrimas/química , Adolescente , Adulto , Variação Biológica Individual , Síndromes do Olho Seco/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Adulto Jovem
14.
Vet J ; 247: 61-64, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30971353

RESUMO

Calprotectin is a useful biomarker of inflammation in dogs. However, the biological variation of serum canine calprotectin is unknown. Indices of biological variation were determined in serial serum samples (n=147) from 11 healthy dogs (males/females: 4/7, median age: 5 years): analytical (3.0%), intra-individual (29.9%), and inter-individual variation (33.2%), reciprocal index of individuality (1.1), and index of heterogeneity (4.9). Serum calprotectin concentrations measured by ELISA and by the previous radioimmunoassay were highly correlated, but a constant and proportional bias exists between both assays. A de novo ELISA-reference interval (RI) for serum calprotectin concentration was established (0.6-11.8mg/L). Moderate changes in serum calprotectin (minimum critical difference: 6.4mg/L) between sequential measurements are needed to be considered relevant, and a population-based RI may or may not be appropriate for serum calprotectin.


Assuntos
Cães/sangue , Ensaio de Imunoadsorção Enzimática/veterinária , Complexo Antígeno L1 Leucocitário/sangue , Animais , Variação Biológica Individual , Cães/imunologia , Feminino , Mediadores da Inflamação/sangue , Masculino
15.
Neuron ; 102(1): 48-59, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30946825

RESUMO

Addiction is a disease in which, after a period of recreational use, a subset of individuals develops compulsive use that does not stop even in light of major negative consequences. Here, we review the evidence for underlying epigenetic remodeling in brain in two settings. First, excessive dopamine signaling during drug use may modulate gene expression, altering synaptic function and circuit activity and leading over time to maladaptive behaviors in vulnerable individuals. Second, on a longer timescale, life experience can shape the epigenetic landscape in brain and thereby may contribute to an individual's vulnerability by amplifying drug-induced changes in gene expression that drive the transition to addiction. We conclude by exploring how epigenetic mechanisms might serve as therapeutic targets for addiction treatments.


Assuntos
Encéfalo/metabolismo , Epigênese Genética/genética , Plasticidade Neuronal/genética , Transtornos Relacionados ao Uso de Substâncias/genética , Sinapses/genética , Transmissão Sináptica/genética , Animais , Variação Biológica Individual , Encéfalo/fisiopatologia , Cromatina/metabolismo , Humanos , Vias Neurais/metabolismo , Vias Neurais/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Sinapses/metabolismo
16.
Am J Physiol Renal Physiol ; 316(6): F1114-F1123, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30908934

RESUMO

Little is known about the population genetics of water balance. A recent meta-genome-wide association study on plasma sodium concentration identified novel loci of high biological plausibility, yet heritability of the phenotype has never been convincingly shown in European ancestry. The present study linked the Vietnam Era Twin Registry with the Department of Veterans Affairs VistA patient care clinical database. Participants (n = 2,370, 59.6% monozygotic twins and 40.4% dizygotic twins) had a median of seven (interquartile range: 3-14) plasma sodium determinations between October 1999 and March 2017. Heritability of the mean plasma sodium concentration among all twins was 0.41 (95% confidence interval: 0.35-0.46) and 0.49 (95% confidence interval: 0.43-0.54) after exclusion of 514 twins with only a single plasma sodium determination. Heritability among Caucasian (n = 1,958) and African-American (n = 268) twins was 0.41 (95% confidence interval: 0.34-0.47) and 0.36 (95% confidence interval: 0.17-0.52), respectively. Exclusion of data from twins who had been prescribed medications known to impact systemic water balance had no effect. The ability of the present study to newly detect substantial heritability across multiple racial groups was potentially a function of the cohort size and relatedness, exclusion of sodium determinations confounded by elevated plasma glucose and/or reduced glomerular filtration rate, transformation of plasma sodium for the independent osmotic effect of plasma glucose, and use of multiple laboratory determinations per individual over a period of years. Individual-level plasma sodium concentration exhibited longitudinal stability (i.e., individuality); the degree to which individual-level means differed from the population mean was substantial, irrespective of the number of determinations. In aggregate, these data establish the heritability of plasma sodium concentration in European ancestry and corroborate its individuality.


Assuntos
Heterogeneidade Genética , Hereditariedade , Sódio/sangue , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Veteranos , Equilíbrio Hidroeletrolítico/genética , Afro-Americanos/genética , Variação Biológica Individual , Bases de Dados Factuais , Grupo com Ancestrais do Continente Europeu/genética , Genética Populacional , Taxa de Filtração Glomerular/genética , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estados Unidos
17.
Yale J Biol Med ; 92(1): 13-20, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30923469

RESUMO

In this study we examined attention-related reaction time (RT) and intra-individual variability (IIV) in younger and older adults using an iPad-based visual search test, in which, for each trial, participants were required to sequentially press a series of on-screen stimuli numbered from 1 to 8. Although overall performance RT was significantly slower, with greater IIV for the older compared to the younger adult group, there was also a disproportionately slowed RT and greater IIV for the first item in the series compared to all other responses within the trial. When the response to the first stimulus was removed from statistical analysis, the significant age-related RT slowing effect remained, but IIV was no longer significantly greater for the older compared to the younger adults. This pattern of results reveals a dichotomy between the preservation of RT and IIV in aging, and one that is strongly related to research methodology. A finding that may account, at least in part, for the outcome heterogeneity in the study of IIV in aging.


Assuntos
Variação Biológica Individual , Processamento Eletrônico de Dados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Tempo de Reação/fisiologia , Adulto Jovem
18.
Neuropsychology ; 33(5): 599-608, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30896235

RESUMO

OBJECTIVE: Intraindividual cognitive variability (IIV), a measure of within-person variability across cognitive measures at a single time point, is associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Little is known regarding brain changes underlying IIV, or the relationship between IIV and functional ability. Therefore, we investigated the association between IIV and cerebral atrophy in AD-vulnerable regions and everyday functioning in nondemented older adults. METHOD: 736 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants (285 cognitively normal [CN]; 451 MCI) underwent neuropsychological testing and serial MRI over 2 years. Linear mixed effects models examined the association between baseline IIV and change in entorhinal cortex thickness, hippocampal volume, and everyday functioning. RESULTS: Adjusting for age, sex, apolipoprotein E genotype, amyloid-ß positivity, and mean level of cognitive performance, higher baseline IIV predicted faster rates of entorhinal and hippocampal atrophy, as well as functional decline. Higher IIV was associated with both entorhinal and hippocampal atrophy among MCI participants but selective vulnerability of the entorhinal cortex among CN individuals. CONCLUSIONS: IIV was associated with more widespread medial temporal lobe (MTL) atrophy in individuals with MCI relative to CN, suggesting that IIV may be tracking advancing MTL pathologic changes across the continuum of aging, MCI, and dementia. Findings suggest that cognitive dispersion may be a sensitive marker of neurodegeneration and functional decline in nondemented older adults. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Envelhecimento/patologia , Envelhecimento/fisiologia , Variação Biológica Individual , Disfunção Cognitiva/patologia , Disfunção Cognitiva/fisiopatologia , Córtex Entorrinal/patologia , Hipocampo/patologia , Idoso , Idoso de 80 Anos ou mais , Atrofia/patologia , Biomarcadores , Disfunção Cognitiva/diagnóstico por imagem , Córtex Entorrinal/diagnóstico por imagem , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
19.
Cardiovasc Diabetol ; 18(1): 42, 2019 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-30922303

RESUMO

Cardiovascular (CV) events or their minor syndromes, as various forms of ischemia, are medical emergencies that do not allow enough time for a guiding anamnesis or proper clinical examination, and lead to relying on Treatment Guidelines, but in many situations it is appropriate to deviate from them. Pathological studies have associated 75% of coronary artery events with atherosclerotic plaque rupture; it is now known that rupture alone is not enough for obstruction or occlusion of the vessel lumen. Concomitant conditions are required for the clinical manifestation of cardiovascular disease, including prothrombogenic and dysfunctional endothelium, less fibrinolytic capacity to protect it, increased platelet activation, increased adrenergic tone, microcirculation vasoconstriction, and other countless factors that contribute to thrombus formation, causing ischemia or infarction. But in most cases, repair of plaque rupture and re endothelization of the lesion are asymptomatic and silent. Atherosclerotic process is a chronic and progressive immune inflammation. Most of the therapeutic indications include statins, which cause side effects in 10% of patients, with a range varying between 7 and 21%, according to different authors. Many investigators have proved that statin use contribute to the genesis of diabetes, reports vary between 1 and 46%, where marked elevation of blood glucose fasting levels and glycosylated hemoglobin have been observed, be it by increased tissue resistance to insulin or by reduced ß-cell insulin secretion. Physicians should base their indications on the recommendations provided by Guidelines, but they should not forget that every patient is different, and they should not get confused due to lack of time in an emergency nor be influenced by the latest publications or techniques until they have been properly tested.


Assuntos
Doenças Cardiovasculares/terapia , Diabetes Mellitus/terapia , Fidelidade a Diretrizes/normas , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Variação Biológica Individual , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Tomada de Decisão Clínica , Comorbidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Medicina Baseada em Evidências/normas , Predisposição Genética para Doença , Nível de Saúde , Humanos , Seleção de Pacientes , Fatores de Risco , Resultado do Tratamento
20.
PLoS One ; 14(3): e0213010, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30845260

RESUMO

Working memory performance is a key indicator of cognitive and developmental status. While recent evidence indicates that stabilizing neural gain supports the stabilization of working memory during adolescence, the computational mechanisms linking neural stabilization to behavior are poorly understood. We develop a mechanistic account of behavior during the memory-guided saccade task based on a stochastic accumulator framework. Results indicate that a specific balance of independent gain signals affecting working memory representations and oculomotor response thresholds can account for a peculiar U-shaped feature of the speed-accuracy relationship. Additionally, aspects of behavioral variability and mean behavioral performance, as well as subtle shifts in the shape of the speed-accuracy relationship across development, can be accounted for by the stabilization of these two sources of variability. Thus, the stabilization of neural variability can, in part, account for developmental improvements in behavioral variability as well as some improvement in mean behavioral performance.


Assuntos
Comportamento do Adolescente/fisiologia , Desenvolvimento do Adolescente/fisiologia , Memória de Curto Prazo/fisiologia , Adolescente , Adulto , Variação Biológica Individual , Criança , Feminino , Humanos , Masculino , Modelos Psicológicos , Estimulação Luminosa , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Movimentos Sacádicos/fisiologia , Adulto Jovem
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