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1.
Proc Natl Acad Sci U S A ; 119(20): e2119434119, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35561220

RESUMO

The ability of eukaryotic cells to differentiate surface stiffness is fundamental for many processes like stem cell development. Bacteria were previously known to sense the presence of surfaces, but the extent to which they could differentiate stiffnesses remained unclear. Here we establish that the human pathogen Pseudomonas aeruginosa actively measures surface stiffness using type IV pili (TFP). Stiffness sensing is nonlinear, as induction of the virulence factor regulator is peaked with stiffness in a physiologically important range between 0.1 kPa (similar to mucus) and 1,000 kPa (similar to cartilage). Experiments on surfaces with distinct material properties establish that stiffness is the specific biophysical parameter important for this sensing. Traction force measurements reveal that the retraction of TFP is capable of deforming even stiff substrates. We show how slow diffusion of the pilin PilA in the inner membrane yields local concentration changes at the base of TFP during extension and retraction that change with substrate stiffness. We develop a quantitative biomechanical model that explains the transcriptional response to stiffness. A competition between PilA diffusion in the inner membrane and a loss/gain of monomers during TFP extension/retraction produces substrate stiffness-dependent dynamics of the local PilA concentration. We validated this model by manipulating the ATPase activity of the TFP motors to change TFP extension and retraction velocities and PilA concentration dynamics, altering the stiffness response in a predictable manner. Our results highlight stiffness sensing as a shared behavior across biological kingdoms, revealing generalizable principles of environmental sensing across small and large cells.


Assuntos
Proteínas de Fímbrias , Fímbrias Bacterianas , Pseudomonas aeruginosa , Proteínas de Fímbrias/genética , Proteínas de Fímbrias/metabolismo , Fímbrias Bacterianas/genética , Fímbrias Bacterianas/fisiologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/patogenicidade , Propriedades de Superfície , Transcrição Gênica
2.
Nitric Oxide ; 148: 23-33, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38697467

RESUMO

Dietary nitrate (NO3-) supplementation can increase nitric oxide (NO) bioavailability, reduce blood pressure (BP) and improve muscle contractile function in humans. Plasma nitrite concentration (plasma [NO2-]) is the most oft-used biomarker of NO bioavailability. However, it is unclear which of several NO biomarkers (NO3-, NO2-, S-nitrosothiols (RSNOs)) in plasma, whole blood (WB), red blood cells (RBC) and skeletal muscle correlate with the physiological effects of acute and chronic dietary NO3- supplementation. Using a randomized, double-blind, crossover design, 12 participants (9 males) consumed NO3--rich beetroot juice (BR) (∼12.8 mmol NO3-) and NO3--depleted placebo beetroot juice (PL) acutely and then chronically (for two weeks). Biological samples were collected, resting BP was assessed, and 10 maximal voluntary isometric contractions of the knee extensors were performed at 2.5-3.5 h following supplement ingestion on day 1 and day 14. Diastolic BP was significantly lower in BR (-2 ± 3 mmHg, P = 0.03) compared to PL following acute supplementation, while the absolute rate of torque development (RTD) was significantly greater in BR at 0-30 ms (39 ± 57 N m s-1, P = 0.03) and 0-50 ms (79 ± 99 N m s-1, P = 0.02) compared to PL following two weeks supplementation. Greater WB [RSNOs] rather than plasma [NO2-] was correlated with lower diastolic BP (r = -0.68, P = 0.02) in BR compared to PL following acute supplementation, while greater skeletal muscle [NO3-] was correlated with greater RTD at 0-30 ms (r = 0.64, P=0.03) in BR compared to PL following chronic supplementation. We conclude that [RSNOs] in blood, and [NO3-] in skeletal muscle, are relevant biomarkers of NO bioavailability which are related to the reduction of BP and the enhanced muscle contractile function following dietary NO3- ingestion in humans.


Assuntos
Biomarcadores , Pressão Sanguínea , Estudos Cross-Over , Suplementos Nutricionais , Nitratos , Óxido Nítrico , Humanos , Nitratos/administração & dosagem , Nitratos/farmacologia , Nitratos/sangue , Masculino , Biomarcadores/sangue , Feminino , Óxido Nítrico/metabolismo , Óxido Nítrico/sangue , Adulto , Método Duplo-Cego , Pressão Sanguínea/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Adulto Jovem , Beta vulgaris/química , Nitritos/sangue
3.
Phys Rev Lett ; 130(21): 218402, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37295076

RESUMO

The bacterium Myxococcus xanthus produces multicellular droplets called fruiting bodies when starved. These structures form initially through the active dewetting of a vegetative biofilm into surface-associated droplets. This motility-driven aggregation is succeeded by a primitive developmental process in which cells in the droplets mature into nonmotile spores. Here, we use atomic force microscopy to probe the mechanics of these droplets throughout their formation. Using a combination of time- and frequency-domain rheological experiments, we characterize and develop a simple model of the linear viscoelasticity of these aggregates. We then use this model to quantify how cellular behaviors predominant at different developmental times-motility during the dewetting phase and cellular sporulation during later development-manifest as decreased droplet viscosity and increased elasticity, respectively.


Assuntos
Myxococcus xanthus , Esporos Bacterianos , Proteínas de Bactérias
4.
Nitric Oxide ; 138-139: 1-9, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37268184

RESUMO

Dietary nitrate (NO3-) supplementation can enhance nitric oxide (NO) bioavailability and lower blood pressure (BP) in humans. The nitrite concentration ([NO2-]) in the plasma is the most commonly used biomarker of increased NO availability. However, it is unknown to what extent changes in other NO congeners, such as S-nitrosothiols (RSNOs), and in other blood components, such as red blood cells (RBC), also contribute to the BP lowering effects of dietary NO3-. We investigated the correlations between changes in NO biomarkers in different blood compartments and changes in BP variables following acute NO3- ingestion. Resting BP was measured and blood samples were collected at baseline, and at 1, 2, 3, 4 and 24 h following acute beetroot juice (∼12.8 mmol NO3-, ∼11 mg NO3-/kg) ingestion in 20 healthy volunteers. Spearman rank correlation coefficients were determined between the peak individual increases in NO biomarkers (NO3-, NO2-, RSNOs) in plasma, RBC and whole blood, and corresponding decreases in resting BP variables. No significant correlation was observed between increased plasma [NO2-] and reduced BP, but increased RBC [NO2-] was correlated with decreased systolic BP (rs = -0.50, P = 0.03). Notably, increased RBC [RSNOs] was significantly correlated with decreases in systolic (rs = -0.68, P = 0.001), diastolic (rs = -0.59, P = 0.008) and mean arterial pressure (rs = -0.64, P = 0.003). Fisher's z transformation indicated no difference in the strength of the correlations between increases in RBC [NO2-] or [RSNOs] and decreased systolic blood pressure. In conclusion, increased RBC [RSNOs] may be an important mediator of the reduction in resting BP observed following dietary NO3- supplementation.


Assuntos
Beta vulgaris , Hipotensão , S-Nitrosotióis , Humanos , Pressão Sanguínea , Nitratos , Nitritos , Dióxido de Nitrogênio , Óxido Nítrico/farmacologia , Suplementos Nutricionais , Eritrócitos , S-Nitrosotióis/farmacologia , Ingestão de Alimentos , Método Duplo-Cego
5.
Nitric Oxide ; 121: 1-10, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35032643

RESUMO

Dietary nitrate (NO3-) ingestion can be beneficial for health and exercise performance. Recently, based on animal and limited human studies, a skeletal muscle NO3- reservoir has been suggested to be important in whole body nitric oxide (NO) homeostasis. The purpose of this study was to determine the time course of changes in human skeletal muscle NO3- concentration ([NO3-]) following the ingestion of dietary NO3-. Sixteen participants were allocated to either an experimental group (NIT: n = 11) which consumed a bolus of ∼1300 mg (12.8 mmol) potassium nitrate (KNO3), or a placebo group (PLA: n = 5) which consumed a bolus of potassium chloride (KCl). Biological samples (muscle (vastus lateralis), blood, saliva and urine) were collected shortly before NIT or PLA ingestion and at intervals over the course of the subsequent 24 h. At baseline, no differences were observed for muscle [NO3-] and [NO2-] between NIT and PLA (P > 0.05). In PLA, there were no changes in muscle [NO3-] or [NO2-] over time. In NIT, muscle [NO3-] was significantly elevated above baseline (54 ± 29 nmol/g) at 0.5 h, reached a peak at 3 h (181 ± 128 nmol/g), and was not different to baseline from 9 h onwards (P > 0.05). Muscle [NO2-] did not change significantly over time. Following ingestion of a bolus of dietary NO3-, skeletal muscle [NO3-] increases rapidly, reaches a peak at ∼3 h and subsequently declines towards baseline values. Following dietary NO3- ingestion, human m. vastus lateralis [NO3-] expressed a slightly delayed pharmacokinetic profile compared to plasma [NO3-].


Assuntos
Músculo Esquelético/química , Nitratos/análise , Nitritos/análise , Adulto , Suplementos Nutricionais , Feminino , Humanos , Masculino , Nitratos/administração & dosagem , Fatores de Tempo , Adulto Jovem
6.
J Sports Sci ; 40(23): 2585-2594, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36759944

RESUMO

The purpose of this study was to investigate effects of concurrent and independent administration of dietary nitrate (NO3-), administered as NO3--rich beetroot juice (BR; ~12.4 mmol of NO3-), and N-acetylcysteine (NAC; 70 mg·kg-1) on physiological responses during prolonged exercise and subsequent high-intensity exercise tolerance. Sixteen recreationally active males supplemented with NO3--depleted beetroot juice (PL) or BR for 6 days and ingested an acute dose of NAC or maltodextrin (MAL) 1 h prior to performing 1 h of heavy-intensity cycling exercise immediately followed by a severe-intensity time-to-exhaustion (TTE) test in four conditions: 1) PL+MAL, 2) PL+NAC, 3) BR+MAL and 4) BR+NAC. Pre-exercise plasma [NO3-] and nitrite ([NO2-]) were elevated following BR+NAC  and BR+MAL (both P < 0.01) compared with PL+NAC and PL+MAL; plasma [cysteine] was increased in PL+NAC  and BR+NAC (both P < 0.01) compared to PL+MAL. Muscle excitability declined over time during the prolonged cycling bout in all conditions  but was better preserved in PL+NAC  compared to BR+NAC (P < 0.01) and PL+MAL (P < 0.05). There was no effect of supplementation on subsequent TTE . These findings indicate that co-ingestion of BR and NAC does not appreciably alter physiological responses during prolonged heavy-intensity cycling or enhance subsequent exercise tolerance.


Assuntos
Acetilcisteína , Suplementos Nutricionais , Exercício Físico , Sucos de Frutas e Vegetais , Nitratos , Extratos Vegetais , Humanos , Masculino , Exercício Físico/fisiologia , Nitratos/sangue , Acetilcisteína/administração & dosagem , Antioxidantes/administração & dosagem , Estudos Cross-Over , Espécies Reativas de Oxigênio , Treino Aeróbico , Consumo de Oxigênio/fisiologia , Nitritos/sangue , Adulto , Extratos Vegetais/farmacologia , Raízes de Plantas
7.
Artigo em Inglês | MEDLINE | ID: mdl-35856134

RESUMO

BACKGROUND: Peripartum antibiotics are commonly administered. Little is known of the attitudes of pregnant women toward peripartum antibiotics. AIM: We aimed to assess the awareness of and attitudes toward peripartum antibiotic use in Australian women. MATERIALS AND METHODS: We surveyed post-partum women at three hospitals over six months. Women reported if they received antibiotics 48 h either side of delivery and responded to statements assessing attitudes to peripartum antibiotic use. Administered antibiotics were recorded. We reported the proportion receiving antibiotics and the proportion aware of receiving them. Participants responded on five-point Likert scales and selected side effects of concern. RESULTS: Participants responding were 248 of 299 (83%, Royal Brisbane and Women's Hospital), 56 of 106 (53%, Caboolture Hospital) and 17 (Redcliffe Hospital, denominator not recorded). Of 183 (57%) receiving antibiotics, 134 (73%) received them pre-delivery only, 18 (10%) post-delivery only and 31 (17%) pre- and post-delivery. Pre-delivery, the most common indication was pre-incisional prophylaxis for caesarean delivery (93 of 160 responses, 58%). Seventy-nine (51%, 156 responses) of those receiving pre-delivery antibiotics were aware. Of 49 women receiving post-delivery antibiotics, 36 (73%) were aware. Most agreed they were worried that pre-delivery antibiotics would affect their baby (198, 62%) and 160 (50%) were concerned about effects on their own microbiome. Most (204, 65%) agreed they would rather not take antibiotics while breastfeeding. CONCLUSION: Many women were unaware of receiving pre-delivery antibiotics. Most had concerns about side effects. Improved communication regarding peripartum antibiotic use would improve patient-centred care.

8.
J Clin Microbiol ; 59(7): e0018221, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-33910964

RESUMO

Rapid and precise detection of Chlamydia trachomatis, the leading global cause of sexually transmitted infections (STI), at the point of care (POC) is required for treatment decisions to prevent transmission and sequelae, including pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, and preterm birth. We developed a rapid POC test (POCT), termed LH-POCT, which uses loop-mediated amplification (LAMP) of nucleic acids. We performed a head-to-head comparison with the Cepheid Xpert CT/NG assay using clinician-collected, deidentified paired vaginal samples from a parent study that consecutively enrolled symptomatic and asymptomatic females over 18 years of age from the Ministry of Health and Medical Services Health Centers in Fiji. Samples were processed by the Xpert CT/NG assay and LH-POCT, blinded to the comparator. Discrepant samples were resolved by quantitative PCR. Deidentified clinical data and tests for Trichomonas vaginalis, Candida, and bacterial vaginosis (BV) were provided. There were a total of 353 samples from 327 females. C. trachomatis positivity was 16.7% (59/353), while the prevalence was 16.82% (55/327) after discrepant resolution. Seven discrepant samples resolved to four false negatives, two false positives, and one true positive for the LH-POCT. The sensitivity of the LH-POCT was 93.65% (95% confidence interval [CI], 84.53% to 98.24%), and specificity was 99.31% (95% CI, 97.53% to 99.92%). Discrepant samples clustered among women with vaginal discharge and/or BV. The prototype LH-POCT workflow has excellent performance, meeting many World Health Organization ASSURED criteria for POC tests, including a sample-to-result time of 35 min. Our LH-POCT holds promise for improving clinical practice to prevent and control C. trachomatis STIs in diverse health care settings globally.


Assuntos
Infecções por Chlamydia , Gonorreia , Nascimento Prematuro , Adolescente , Adulto , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis/genética , Feminino , Fiji , Humanos , Recém-Nascido , Neisseria gonorrhoeae , Testes Imediatos , Gravidez
9.
Proc Natl Acad Sci U S A ; 115(51): 12979-12984, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30498027

RESUMO

Bacteria under external stress can reveal unexpected emergent phenotypes. We show that the intensely studied bacterium Escherichia coli can transform into long, highly motile helical filaments poized at a torsional buckling criticality when exposed to minimum inhibitory concentrations of several antibiotics. While the highly motile helices are physically either right- or left-handed, the motile helices always rotate with a right-handed angular velocity [Formula: see text], which points in the same direction as the translational velocity [Formula: see text] of the helix. Furthermore, these helical cells do not swim by a "run and tumble" but rather synchronously flip their spin [Formula: see text] and thus translational velocity-backing up rather than tumbling. By increasing the translational persistence length, these dynamics give rise to an effective diffusion coefficient up to 20 times that of a normal E. coli cell. Finally, we propose an evolutionary mechanism for this phenotype's emergence whereby the increased effective diffusivity provides a fitness advantage in allowing filamentous cells to more readily escape regions of high external stress.


Assuntos
Escherichia coli/efeitos dos fármacos , Evolução Biológica , Movimento Celular/efeitos dos fármacos , Quimiotaxia , Escherichia coli/fisiologia , Escherichia coli/ultraestrutura , Testes de Sensibilidade Microbiana , Estresse Fisiológico
10.
J Physiol ; 597(23): 5565-5576, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31350908

RESUMO

KEY POINTS: Nitric oxide (NO), a potent vasodilator and a regulator of many physiological processes, is produced in mammals both enzymatically and by reduction of nitrite and nitrate ions. We have previously reported that, in rodents, skeletal muscle serves as a nitrate reservoir, with nitrate levels greatly exceeding those in blood or other internal organs, and with nitrate being reduced to NO during exercise. In the current study, we show that nitrate concentration is substantially greater in skeletal muscle than in blood and is elevated further by dietary nitrate ingestion in human volunteers. We also show that high-intensity exercise results in a reduction in the skeletal muscle nitrate store following supplementation, likely as a consequence of its reduction to nitrite and NO. We also report the presence of sialin, a nitrate transporter, and xanthine oxidoreductase in human skeletal muscle, indicating that muscle has the necessary apparatus for nitrate transport, storage and metabolism. ABSTRACT: Rodent skeletal muscle contains a large store of nitrate that can be augmented by the consumption of dietary nitrate. This muscle nitrate reservoir has been found to be an important source of nitrite and nitric oxide (NO) via its reduction by tissue xanthine oxidoreductase. To explore if this pathway is also active in human skeletal muscle during exercise, and if it is sensitive to local nitrate availability, we assessed exercise-induced changes in muscle nitrate and nitrite concentrations in young healthy humans, under baseline conditions and following dietary nitrate consumption. We found that baseline nitrate and nitrite concentrations were far higher in muscle than in plasma (∼4-fold and ∼29-fold, respectively), and that the consumption of a single bolus of dietary nitrate (12.8 mmol) significantly elevated nitrate concentration in both plasma (∼19-fold) and muscle (∼5-fold). Consistent with these observations, and with previous suggestions of active muscle nitrate transport, we present western blot data to show significant expression of the active nitrate/nitrite transporter sialin in human skeletal muscle. Furthermore, we report an exercise-induced reduction in human muscle nitrate concentration (by ∼39%), but only in the presence of an increased muscle nitrate store. Our results indicate that human skeletal muscle nitrate stores are sensitive to dietary nitrate intake and may contribute to NO generation during exercise. Together, these findings suggest that skeletal muscle plays an important role in the transport, storage and metabolism of nitrate in humans.


Assuntos
Suplementos Nutricionais , Exercício Físico/fisiologia , Músculo Esquelético/metabolismo , Nitratos/metabolismo , Adolescente , Adulto , Feminino , Humanos , Pulmão/metabolismo , Masculino , Nitratos/administração & dosagem , Nitratos/sangue , Nitritos/sangue , Nitritos/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Consumo de Oxigênio , Simportadores/metabolismo , Xantina Desidrogenase/metabolismo , Adulto Jovem
11.
J Sports Sci ; 37(8): 902-910, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30387374

RESUMO

PURPOSE: To determine the accuracy of critical power (CP) and W' (the curvature constant of the power-duration relationship) derived from self-paced time-trial (TT) prediction trials using mobile power meters to predict 16.1-km road cycling TT performance. This study also aimed to assess the agreement between functional threshold power (FTP) and CP. METHODS: Twelve competitive male cyclists completed an incremental test to exhaustion, a FTP test and 4-5 self-paced TT bouts on a stationary bike within the lab, and a 16.1 km road TT, using mobile power meters. RESULTS: CP and W' derived from the power-duration relationship closely predicted TT performance. The 16.1-km road TT completion time (26.7 ± 2.2 min) was not significantly different from and was significantly correlated with the predicted time-to-completion (27.5 ± 3.3 min, r = 0.89, P < 0.01). CP and FTP were not significantly different (275 ± 40 W vs. 278 ± 42 W, P > 0.05); however, the limits of agreement between CP and FTP were 30 to -36 W. DISCUSSION: The findings of this study indicate that CP and W' determined using mobile power meters during maximal, self-paced TT prediction trials can be used to accurately predict 16.1-km cycling performance, supporting the application of the CP and W' for performance prediction. However, the limits of agreement were too large to consider FTP and CP interchangeable.


Assuntos
Desempenho Atlético/fisiologia , Ciclismo/fisiologia , Teste de Esforço/métodos , Adulto , Teste de Esforço/instrumentação , Humanos , Masculino , Consumo de Oxigênio , Troca Gasosa Pulmonar , Equipamentos Esportivos , Fatores de Tempo
13.
Eur Heart J ; 37(46): 3434-3439, 2016 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-26543045

RESUMO

Advanced heart failure is a growing epidemic that leads to significant suffering and economic losses. The development of left ventricular assist devices (LVADs) has led to improved quality of life and long-term survival for patients diagnosed with this devastating condition. This review briefly summarizes the short history and clinical outcomes of LVADs and focuses on the current controversies and issues facing LVAD therapy. Finally, the future directions for the role of LVADs in the treatment of end-stage heart failure are discussed.


Assuntos
Coração Auxiliar , Insuficiência Cardíaca , Humanos , Qualidade de Vida
14.
J Physiol ; 594(15): 4407-23, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-26940850

RESUMO

KEY POINTS: The power-asymptote (critical power; CP) of the hyperbolic power-time relationship for high-intensity exercise defines a threshold between steady-state and non-steady-state exercise intensities and the curvature constant (W') indicates a fixed capacity for work >CP that is related to a loss of muscular efficiency. The present study reports novel evidence on the muscle metabolic underpinnings of CP and W' during whole-body exercise and their relationships to muscle fibre type. We show that the W' is not correlated with muscle fibre type distribution and that it represents an elevated energy contribution from both oxidative and glycolytic/glycogenolytic metabolism. We show that there is a positive correlation between CP and highly oxidative type I muscle fibres and that muscle metabolic steady-state is attainable CP. Our findings indicate a mechanistic link between the bioenergetic characteristics of muscle fibre types and the power-time relationship for high-intensity exercise. ABSTRACT: We hypothesized that: (1) the critical power (CP) will represent a boundary separating steady-state from non-steady-state muscle metabolic responses during whole-body exercise and (2) that the CP and the curvature constant (W') of the power-time relationship for high-intensity exercise will be correlated with type I and type IIx muscle fibre distributions, respectively. Four men and four women performed a 3 min all-out cycling test for the estimation of CP and constant work rate (CWR) tests slightly >CP until exhaustion (Tlim ), slightly CP Tlim isotime to test the first hypothesis. Eleven men performed 3 min all-out tests and donated muscle biopsies to test the second hypothesis. Below CP, muscle [PCr] [42.6 ± 7.1 vs. 49.4 ± 6.9 mmol (kg d.w.)(-1) ], [La(-) ] [34.8 ± 12.6 vs. 35.5 ± 13.2 mmol (kg d.w.)(-1) ] and pH (7.11 ± 0.08 vs. 7.10 ± 0.11) remained stable between ∼12 and 24 min (P > 0.05 for all), whereas these variables changed with time >CP such that they were greater [[La(-) ] 95.6 ± 14.1 mmol (kg d.w.)(-1) ] and lower [[PCr] 24.2 ± 3.9 mmol (kg d.w.)(-1) ; pH 6.84 ± 0.06] (P < 0.05) at Tlim (740 ± 186 s) than during the

Assuntos
Ciclismo/fisiologia , Exercício Físico/fisiologia , Fibras Musculares Esqueléticas/fisiologia , Adulto , Metabolismo Energético , Fadiga/fisiopatologia , Feminino , Humanos , Masculino , Adulto Jovem
15.
J Child Psychol Psychiatry ; 57(8): 927-37, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27090613

RESUMO

BACKGROUND: Machine learning (ML) provides novel opportunities for human behavior research and clinical translation, yet its application can have noted pitfalls (Bone et al., 2015). In this work, we fastidiously utilize ML to derive autism spectrum disorder (ASD) instrument algorithms in an attempt to improve upon widely used ASD screening and diagnostic tools. METHODS: The data consisted of Autism Diagnostic Interview-Revised (ADI-R) and Social Responsiveness Scale (SRS) scores for 1,264 verbal individuals with ASD and 462 verbal individuals with non-ASD developmental or psychiatric disorders, split at age 10. Algorithms were created via a robust ML classifier, support vector machine, while targeting best-estimate clinical diagnosis of ASD versus non-ASD. Parameter settings were tuned in multiple levels of cross-validation. RESULTS: The created algorithms were more effective (higher performing) than the current algorithms, were tunable (sensitivity and specificity can be differentially weighted), and were more efficient (achieving near-peak performance with five or fewer codes). Results from ML-based fusion of ADI-R and SRS are reported. We present a screener algorithm for below (above) age 10 that reached 89.2% (86.7%) sensitivity and 59.0% (53.4%) specificity with only five behavioral codes. CONCLUSIONS: ML is useful for creating robust, customizable instrument algorithms. In a unique dataset comprised of controls with other difficulties, our findings highlight the limitations of current caregiver-report instruments and indicate possible avenues for improving ASD screening and diagnostic tools.


Assuntos
Algoritmos , Transtorno do Espectro Autista/diagnóstico , Escalas de Graduação Psiquiátrica , Máquina de Vetores de Suporte , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Eur J Appl Physiol ; 116(11-12): 2415-2422, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27787608

RESUMO

PURPOSE: The parameters of the power-duration relationship (i.e., the critical power, CP, and the curvature constant, W') may theoretically predict maximal performance capability for exercise above the CP. The CP and W' are associated with the parameters of oxygen uptake ([Formula: see text]O2) kinetics, which can be altered by manipulation of the work-rate forcing function. We tested the hypothesis that the CP and W' derived from constant work-rate (CWR) prediction trials would overestimate ramp incremental exercise performance. METHODS: Thirty subjects (males, n = 28; females, n = 2) performed a ramp incremental test, and 3-5 CWR prediction trials for the determination of the CP and W'. Multiple ramp incremental tests and corresponding CP and W' estimates were available for some subjects such that in total 51 ramp test performances were predicted. RESULTS: The ramp incremental test performance (729 ± 113 s) was overestimated by the CP and W' estimates derived from the best (751 ± 114 s, P < 0.05) and worst (749 ± 111 s, P < 0.05) individual fits of CWR prediction trial data. The error in the prediction was inversely correlated with the magnitude of the W' for the best (r = -0.56, P < 0.05) and worst individual fits (r = -0.36, P < 0.05). CONCLUSIONS: The overestimation of ramp incremental performance suggests that the CP and W' derived from different work-rate forcing functions, thus resulting in different [Formula: see text]O2 kinetics, cannot be used interchangeably. The present findings highlight a potential source of error in performance prediction that is of importance to both researchers and applied practitioners.


Assuntos
Algoritmos , Teste de Esforço/métodos , Treinamento Intervalado de Alta Intensidade/métodos , Consumo de Oxigênio/fisiologia , Esforço Físico/fisiologia , Análise e Desempenho de Tarefas , Adulto , Simulação por Computador , Feminino , Humanos , Masculino , Modelos Biológicos , Força Muscular , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
Eur J Appl Physiol ; 115(9): 1825-34, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25846114

RESUMO

UNLABELLED: It is possible that dietary nitrate (NO3 (-)) supplementation may improve both physical and cognitive performance via its influence on blood flow and cellular energetics. PURPOSE: To investigate the effects of dietary NO3 (-) supplementation on exercise performance and cognitive function during a prolonged intermittent sprint test (IST) protocol, which was designed to reflect typical work patterns during team sports. METHODS: In a double-blind randomised crossover study, 16 male team-sport players received NO3 (-)-rich (BR; 140 mL day(-1); 12.8 mmol of NO3 (-)), and NO3 (-)-depleted (PL; 140 mL day(-1); 0.08 mmol NO3 (-)) beetroot juice for 7 days. On day 7 of supplementation, subjects completed the IST (two 40-min "halves" of repeated 2-min blocks consisting of a 6-s "all-out" sprint, 100-s active recovery and 20 s of rest), on a cycle ergometer during which cognitive tasks were simultaneously performed. RESULTS: Total work done during the sprints of the IST was greater in BR (123 ± 19 kJ) compared to PL (119 ± 17 kJ; P < 0.05). Reaction time of response to the cognitive tasks in the second half of the IST was improved in BR compared to PL (BR first half: 820 ± 96 vs. second half: 817 ± 86 ms; PL first half: 824 ± 114 vs. second half: 847 ± 118 ms; P < 0.05). There was no difference in response accuracy. CONCLUSIONS: These findings suggest that dietary NO3 (-) enhances repeated sprint performance and may attenuate the decline in cognitive function (and specifically reaction time) that may occur during prolonged intermittent exercise.


Assuntos
Desempenho Atlético/fisiologia , Cognição/fisiologia , Suplementos Nutricionais , Exercício Físico/fisiologia , Nitratos/administração & dosagem , Corrida/fisiologia , Administração Oral , Cognição/efeitos dos fármacos , Método Duplo-Cego , Humanos , Nitratos/farmacocinética , Esforço Físico/efeitos dos fármacos , Esforço Físico/fisiologia , Resultado do Tratamento , Adulto Jovem
18.
bioRxiv ; 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38853967

RESUMO

Many bacteria inhabit thin layers of water on solid surfaces both naturally in soils or on hosts or textiles and in the lab on agar hydrogels. In these environments, cells experience capillary forces, yet an understanding of how these forces shape bacterial collective behaviors remains elusive. Here, we show that the water menisci formed around bacteria lead to capillary attraction between cells while still allowing them to slide past one another. We develop an experimental apparatus that allows us to control bacterial collective behaviors by varying the strength and range of capillary forces. Combining 3D imaging and cell tracking with agent-based modeling, we demonstrate that capillary attraction organizes rod-shaped bacteria into densely packed, nematic groups, and profoundly influences their collective dynamics and morphologies. Our results suggest that capillary forces may be a ubiquitous physical ingredient in shaping microbial communities in partially hydrated environments.

19.
Free Radic Biol Med ; 2024 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-39401733

RESUMO

Dietary nitrate (NO3-) supplementation has been shown to reduce blood pressure (BP), improve exercise performance, and alter the oral microbiome. Following a "control" diet (CON), we manipulated dietary NO3- intake to examine the effect of a short-term (7-day) low NO3- diet (LOW) followed by a 3-day high NO3- diet (HIGH), compared to a 7-day standard (STD) NO3- diet followed by HIGH, on saliva, plasma, and muscle [NO3-] and nitrite [NO2-], BP, and cycling exercise performance in healthy young adults. We also examined the effect of LOW on the oral microbiome. Saliva [NO3-] and [NO2-], and plasma [NO3-] were significantly lower than CON following LOW (all P<0.05) but there was no change in plasma [NO2-] or muscle [NO3-] and [NO2-] (all P>0.05). Following HIGH, saliva and plasma [NO3-] and [NO2-], and muscle [NO3-], were significantly elevated above CON, LOW and STD (all P<0.05), but there was no difference between CON-LOW-HIGH and CON-STD-HIGH (P<0.05). BP and exercise performance were not altered following LOW (P>0.05). HIGH significantly reduced systolic and diastolic BP compared to CON when preceded by STD (both P<0.05) but not when preceded by LOW (P>0.05). Peak (+4%) and mean (+3%) power output during sprint cycling was significantly improved following HIGH (both P<0.05), with no differences between CON-LOW-HIGH and CON-STD-HIGH (both P>0.05). LOW altered the oral microbiome composition, including decreases in relative abundances of phylum Proteobacteria and genus Neisseria. The findings indicate that a short-term low NO3- diet lowers plasma but not skeletal muscle [NO3-]. The maintenance of plasma [NO2-] and muscle [NO3-] and [NO2-] following LOW may be indicative of their importance to biological functions, including BP regulation and exercise performance.

20.
Langmuir ; 29(8): 2588-94, 2013 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-23360324

RESUMO

We explore the role of polymer chains on deposition of colloidal particles at solid surfaces from drying aqueous drops and show that the kinetics of phase separation of colloids and polymers can be explained by spinodal decomposition of binary systems. Concentrations of polymer solutions and polymer chain lengths were varied to understand the aggregation dynamics of colloidal particles via a polymer bridging mechanism. We show that when polymer concentration in the droplet is increased, particles spatially order upon drying due to a combination of the phase separation of highly bridged particles and the Marangoni flow effect. The demonstrated effect of particle-adsorbing, water-soluble polymers on the coffee-ring formation opens up new ways of creating highly ordered, long-range patterned surfaces using a facile, template-free approach.


Assuntos
Poliestirenos/química , Coloides/química , Tamanho da Partícula , Propriedades de Superfície , Água/química
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