271 research outputs found

    The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H\u3csub\u3e2\u3c/sub\u3e0\u3csub\u3e2\u3c/sub\u3e and plays an integral role in insulin signal transduction

    Get PDF
    Insulin stimulation of target cells elicits a burst of H2O2 that enhances tyrosine phosphorylation of the insulin receptor and its cellular substrate proteins as well as distal signaling events in the insulin action cascade. The molecular mechanism coupling the insulin receptor with the cellular oxidant-generating apparatus has not been elucidated. Using reverse transcription-PCR and Northern blot analyses, we found that Nox4, a homolog of gp91phox, the phagocytic NAD(P)H oxidase catalytic subunit, is prominently expressed in insulin-sensitive adipose cells. Adenovirus-mediated expression of Nox4 deletion constructs lacking NAD(P)H or FAD/NAD(P)H cofactor binding domains acted in a dominant-negative fashion in differentiated 3T3-L1 adipocytes and attenuated insulin-stimulated H2O2 generation, insulin receptor (IR) and IRS-1 tyrosine phosphorylation, activation of downstream serine kinases, and glucose uptake. Transfection of specific small interfering RNA oligonucleotides reduced Nox4 protein abundance and also inhibited the insulin signaling cascade. Overexpression of Nox4 also significantly reversed the inhibition of insulin-stimulated IR tyrosine phosphorylation induced by coexpression of PTP1B by inhibiting PTP1B catalytic activity. These data suggest that Nox4 provides a novel link between the IR and the generation of cellular reactive oxygen species that enhance insulin signal transduction, at least in part via the oxidative inhibition of cellular protein-tyrosine phosphatases (PTPases), including PTP1B, a PTPase that has been previously implicated in the regulation of insulin action

    Challenges and opportunities for the future of Brain-Computer Interface in neurorehabilitation

    Get PDF
    Brain-computer interfaces (BCIs) provide a unique technological solution to circumvent the damaged motor system. For neurorehabilitation, the BCI can be used to translate neural signals associated with movement intentions into tangible feedback for the patient, when they are unable to generate functional movement themselves. Clinical interest in BCI is growing rapidly, as it would facilitate rehabilitation to commence earlier following brain damage and provides options for patients who are unable to partake in traditional physical therapy. However, substantial challenges with existing BCI implementations have prevented its widespread adoption. Recent advances in knowledge and technology provide opportunities to facilitate a change, provided that researchers and clinicians using BCI agree on standardisation of guidelines for protocols and shared efforts to uncover mechanisms. We propose that addressing the speed and effectiveness of learning BCI control are priorities for the field, which may be improved by multimodal or multi-stage approaches harnessing more sensitive neuroimaging technologies in the early learning stages, before transitioning to more practical, mobile implementations. Clarification of the neural mechanisms that give rise to improvement in motor function is an essential next step towards justifying clinical use of BCI. In particular, quantifying the unknown contribution of non-motor mechanisms to motor recovery calls for more stringent control conditions in experimental work. Here we provide a contemporary viewpoint on the factors impeding the scalability of BCI. Further, we provide a future outlook for optimal design of the technology to best exploit its unique potential, and best practices for research and reporting of findings

    Stop-Signal Reaction Time Correlates With a Compensatory Balance Response

    Get PDF
    Background Response inhibition involves suppressing automatic, but unwanted action, which allows for behavioral flexibility. This capacity could theoretically contribute to fall prevention, especially in the cluttered environments we face daily. Although much has been learned from cognitive psychology regarding response inhibition, it is unclear if such findings translate to the intensified challenge of coordinating balance recovery reactions. Research question Is the ability to stop a prepotent response preserved when comparing performance on a standard test of response inhibition versus a reactive balance test where compensatory steps must be occasionally suppressed? Methods Twelve young adults completed a stop signal task and reactive balance test separately. The stop signal task evaluates an individual’s ability to quickly suppress a visually-cued button press upon hearing a ‘stop’ tone, and provides a measure of the speed of response inhibition called the Stop Signal Reaction Time (SSRT). Reactive balance was tested by releasing participants from a supported lean position, in situations where the environment was changed during visual occlusion. Upon receiving vision, participants were required to either step to regain balance following cable release (70% of trials), or suppress a step if an obstacle was present (30% of trials). The early muscle response of the stepping leg was compared between the ‘step blocked’ and ‘step allowed’ trials to quantify step suppression. Results SSRT was correlated with muscle activation of the stepping leg when sufficient time was provided to view the response environment (400 ms). Individuals with faster SSRTs exhibited comparably less leg muscle activity when a step was blocked, signifying a superior ability to inhibit an unwanted step. Significance Performance on a standardized test of response inhibition is related to performance on a reactive balance test where automated stepping responses must occasionally be inhibited. This highlights a generalizable neural mechanism for stopping action across different behavioral contexts

    Proyecto de inversión para la implementación de una empresa de administración, almacenamiento y digitalización de documentos (archivos pasivos) en la ciudad de Guayaquil

    Get PDF
    El proyecto de implementación de una empresa de administración, almacenamiento y digitalización de archivos pasivos en la ciudad de Guayaquil nace de la idea de tres estudiantes universitarios que desean conocer la factibilidad de este proyecto. Para esto, el amplio conocimiento de las diferentes técnicas aprendidas durante su carrera profesional ha ayudado a determinar paso a paso las metodologías necesarias para aplicarlas y conocer más de esta idea de negocio. Al principio, se conoce que este servicio es poco desarrollado en la ciudad de Guayaquil ya que las empresas existentes en el mercado no ofrecen un servicio completo para la gestión de documentos, tomando en cuenta que las organizaciones desean hacer mejor uso de su infraestructura y tiempo, dejando a terceros el manejo completo en la administración y almacenamiento de los archivos pasivos. A pesar de la gran complejidad que este negocio involucra, dada por su fuerte inversión inicial y por la falta credibilidad en el tipo de servicio que se ofrece, el estudio realizado muestra que existe una gran demanda insatisfecha, dejando una oportunidad de negocio por cubrir en el mercado guayaquileño. Además, la determinación de ingresos, costos y demás variables que se involucran en el desenvolvimiento fueron definidas durante el trayecto de la investigación, denominando una idea atractiva y rentable de implementar en la ciudad de Guayaquil

    Estrategias de comercio electrónico y su influencia en la decisión de compra online en los clientes de la Empresa Costa Gas Trujillo 2017

    Get PDF
    La presente investigación se realizó con el propósito de determinar cómo las estrategias de comercio electrónico influyeron en la decisión de compra online de los clientes de la empresa Costa Gas Trujillo. Este trabajo se ha desarrollado con el método de diseño transeccional de tipo causal, por cuanto los datos se tomaron de una muestra de 229 clientes de la empresa, previa aplicación de una prueba piloto mediante instrumentos de recolección de datos elaborados por los autores. Luego se procedió a la tabulación y vaciado de los datos. Para el análisis de los datos estadísticos obtenidos se emplearon tablas y gráficos que permitieron elaborar la interpretación de los mismos, cuyos resultados serán útiles para evaluar las estrategias de comercio electrónico que brinda la empresa Costa Gas Trujillo-Se ha concluido que, de las estrategias de comercio electrónico aplicadas, la interacción y fidelización tienen un impacto medio, pero de gran consideración en la decisión de compra online de los clientes de Costa Gas Trujillo, mientras que la estrategia de control presenta una enorme variación en cuanto a las demás, esto debido a que el cliente desea establecer su condición de consumidor teniendo amplio dominio de las alternativas de compra que tiene. Asimismo, se muestra cierta resistencia a efectuar compras online a causa del temor del mal uso de sus datos personales, siendo un punto de quiebre en la investigación.This research was conducted in order to determine how strategies of e commerce influence in the online purchase decision of the Costa Gas Trujillo’s customers.This research was developed with the transectional of causal type design method of testing; also data was taken from 229 customers, previous application of a pilot test with data recollection instruments developed by the authors. Then it proceeded to the tabulation and emptying data. To analyze the obtained statistical data, tables and graphs were used that permitted the interpretation, and the results will be useful to value the Costa Gas Trujillo e commerce strategies. It has been concluded that from the applied e commerce strategies, interaction and loyalty show a medium impact, but, at the same time, with a great consideration in the Costa Gas Trujillo online purchase decision’s customers, meanwhile control strategy shows a high level variation with the others, this happens because the customer wants to have all the control of the purchase choices. Also it is shown some resistance to buy online, all this for customers scare of the bad use of their personal info, being the breaking point of this research.Tesi

    Session availability as a result of prior injury impacts the risk of subsequent injury in elite male Australian footballers

    Get PDF
    Prior injury is a commonly identified risk factor for subsequent injury. However, a binary approach to classifying prior injury (i.e., yes/no) is commonly implemented and may constrain scientific findings, as it is possible that variations in the amount of time lost due to an injury will impact subsequent injury risk to differing degrees. Accordingly, this study investigated whether session availability, a surrogate marker of prior injury, influenced the risk of subsequent non-contact lower limb injury in Australian footballers. Data were collected from 62 male elite Australian footballers throughout the 2015, 2016, and 2017 Australian Football League seasons. Each athlete’s participation status (i.e., full or missed/modified) and any injuries that occurred during training sessions/matches were recorded. As the focus of the current study was prior injury, any training sessions/matches that were missed due to reasons other than an injury (e.g., load management, illness and personal reasons) were removed from the data prior to all analyses. For every Monday during the in-season periods, session availability (%) in the prior 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, and 84 days was determined as the number of training sessions/matches fully completed (injury free) relative to the number of training sessions/matches possible in each window. Each variable was modeled using logistic regression to determine its impact on subsequent injury risk. Throughout the study period, 173 non-contact lower limb injuries that resulted in at least one missed/modified training session or match during the in-season periods occurred. Greater availability in the prior 7 days increased injury probabilities by up to 4.4%. The impact of session availability on subsequent injury risk diminished with expanding windows (i.e., availability in the prior 14 days through to the prior 84 days). Lesser availability in the prior 84 days increased injury probabilities by up to 14.1%, only when coupled with greater availability in the prior 7 days. Session availability may provide an informative marker of the impact of prior injury on subsequent injury risk and can be used by coaches and clinicians to guide the progression of training, particularly for athletes that are returning from long periods of injury

    Modeling the Risk of Team Sport Injuries: A Narrative Review of Different Statistical Approaches

    Get PDF
    Injuries are a common occurrence in team sports and can have significant financial, physical and psychological consequences for athletes and their sporting organizations. As such, an abundance of research has attempted to identify factors associated with the risk of injury, which is important when developing injury prevention and risk mitigation strategies. There are a number of methods that can be used to identify injury risk factors. However, difficulty in understanding the nuances between different statistical approaches can lead to incorrect inferences and decisions being made from data. Accordingly, this narrative review aims to (1) outline commonly implemented methods for determining injury risk, (2) highlight the differences between association and prediction as it relates to injury and (3) describe advances in statistical modeling and the current evidence relating to predicting injuries in sport. Based on the points that are discussed throughout this narrative review, both researchers and practitioners alike need to carefully consider the different types of variables that are examined in relation to injury risk and how the analyses pertaining to these different variables are interpreted. There are a number of other important considerations when modeling the risk of injury, such as the method of data transformation, model validation and performance assessment. With these technical considerations in mind, researchers and practitioners should consider shifting their perspective of injury etiology from one of reductionism to one of complexity. Concurrently, research implementing reductionist approaches should be used to inform and implement complex approaches to identifying injury risk. However, the ability to capture large injury numbers is a current limitation of sports injury research and there has been a call to make data available to researchers, so that analyses and results can be replicated and verified. Collaborative efforts such as this will help prevent incorrect inferences being made from spurious data and will assist in developing interventions that are underpinned by sound scientific rationale. Such efforts will be a step in the right direction of improving the ability to identify injury risk, which in turn will help improve risk mitigation and ultimately the prevention of injuries

    Infrastructure Alignment

    Get PDF
    The academic library makes various commitments to infrastructure support, development, and maintenance in support of its scholarly publishing programs. Infrastructure may be collaborative, exploratory, innovative, or outsourced. How do library-based publishing programs make such commitments, and what initiatives presently underway will provide the next wave of infrastructure options. And further, how does the academic library context inform setup and infrastructure choices in ways that are distinct from similar decisions across the scholarly publishing landscape

    The dose-response of the nordic hamstring exercise on biceps femoris architecture and eccentric knee flexor strength : A randomized interventional trial

    Get PDF
    Purpose: To examine the dose–response of the Nordic hamstring exercise (NHE) on biceps femoris long head (BFlh) architecture and eccentric knee flexor strength. Design: Randomized interventional trial. Methods: Forty recreationally active males completed a 6-week NHE training program consisting of either intermittent low volumes (group 1; n = 10), low volumes (group 2; n = 10), initial high volumes followed by low volumes (group 3; n = 10), or progressively increasing volumes (group 4; n = 10). A 4-week detraining period followed each program. Muscle architecture was assessed weekly during training and after 2 and 4 weeks of detraining. Eccentric knee flexor strength was assessed preintervention and postintervention and after 2 and 4 weeks of detraining. Results: Following 6 weeks of training, BFlh fascicle length (FL) increased in group 3 (mean difference = 0.83 cm, d = 0.45, P = .027, +7%) and group 4 (mean difference = 1.48 cm, d = 0.94, P = .004, +14%). FL returned to baseline following detraining in groups 3 and 4. Strength increased in group 2 (mean difference = 53.6 N, d = 0.55, P = .002, +14%), group 3 (mean difference = 63.4 N, d = 0.72, P = .027, +17%), and group 4 (mean difference = 74.7, d = 0.83, P = .006, +19%) following training. Strength returned to baseline following detraining in groups 2 and 3 but not in group 4. Conclusions: Initial high volumes of the NHE followed by lower volumes, as well as progressively increasing volumes, can elicit increases in BFlh FL and eccentric knee flexor strength. Low volumes of the NHE were insufficient to increase FL, although as few as 48 repetitions in 6 weeks did increase strength

    Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting

    Get PDF
    BACKGROUND We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. METHODS In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3–receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide–doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. RESULTS In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P = 0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P = 0.002), and the overall 120-hour period (37% vs. 22%, P = 0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P = 0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. CONCLUSIONS Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.
    • …
    corecore