Plos One
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A key problem in neuroscience is understanding how the brain makes decisions under uncertainty. Important insights have been gained using tasks such as the random dots motion discrimination task in which the subject makes decisions based on noisy stimuli. A descriptive model known as the drift diffusion model has previously been used to explain psychometric and reaction time data from such tasks but to fully explain the data, one is forced to make ad-hoc assumptions such as a time-dependent collapsing decision boundary. ⋯ We show that the motion discrimination task reduces to the problems of (1) computing beliefs (posterior distributions) over the unknown direction and motion strength from noisy observations in a bayesian manner, and (2) selecting actions based on these beliefs to maximize the expected sum of future rewards. The resulting optimal policy (belief-to-action mapping) is shown to be equivalent to a collapsing decision threshold that governs the switch from evidence accumulation to a discrimination decision. We show that the model accounts for both accuracy and reaction time as a function of stimulus strength as well as different speed-accuracy conditions in the random dots task.
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C-reactive Protein (CRP) is used next to clinical scoring systems to recognize critically ill patients prone to develop complications on the Intensive Care Unit (ICU). The purpose of this study is to assess the predictive value of CRP as parameter for clinical deterioration and/or clinical decision making as ordering diagnostic procedures or performing (re)interventions. Also, we wanted to determine the value of CRP in early detection of surgical complications in the critically ill general surgical patient in the ICU and its interpretation in adjunct to a clinical scoring system, the Sequential Organ Failure Assessment Score. ⋯ An increase in C-reactive protein is a poor parameter for early detection of complications in the critically ill surgical patient in the ICU by means of diagnostic procedures or therapeutic (re)-interventions.
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Inhalation of crystalline silica (CS) particles increases the risk of pulmonary tuberculosis; however, the precise mechanism through which CS exposure facilitates Mycobacterium tuberculosis (Mtb) infection is unclear. We speculate that macrophage exposure to CS deregulates the cell death pathways that could explain, at least in part, the association observed between exposure to CS and pulmonary tuberculosis. We therefore established an in vitro model in which macrophages were exposed to CS and then infected with Mtb. ⋯ This pro-inflammatory profile of the macrophage unbalanced the apoptosis/necrosis pathway. Taken together, these data suggest that macrophages exposed to CS are sensitized to cell death by MAPK kinase-dependent signaling pathway. Secretion of TNF-α and IL-1β by Mtb-infected macrophages promotes necrosis, and this deregulation of cell death pathways may favor the release of viable bacilli, thus leading to the progression of tuberculosis.
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Dexmedetomidine (DEX) has been used under perioperative settings as an adjuvant to enhance the analgesic property of local anesthetics by some anesthesiologists. However, the analgesic mechanisms and neurotoxicity of DEX were poorly understood. This study examined the effect of DEX alone on inflammatory pain, and it also examined the underlying molecular mechanisms of DEX in the spinal cord. Furthermore, in vivo and in vitro experiments were performed to investigate the neurotoxicity of DEX on the spinal cord and cortical neurons. ⋯ Intrathecal injection of DEX alone or as an adjuvant might be potential for pain relief.
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The aim of the present study was to test the hypotheses that 1) a single exercise bout increases UCP1 mRNA in both inguinal (i)WAT and epididymal (e)WAT, 2) UCP1 expression and responsiveness to exercise are different in iWAT and eWAT, 3) PGC-1α determines the basal levels of UCP1 and PRDM16 in WAT and 4) exercise and exercise training regulate UCP1 and PRDM16 expression in WAT in a PGC-1α-dependent manner. ⋯ The present observations provide evidence that exercise training increases UCP1 protein in iWAT through PGC-1α, likely as a cumulative effect of transient increases in UCP1 expression after each exercise bout. Moreover, the results suggest that iWAT is more responsive than eWAT in exercise-induced regulation of UCP1. In addition, as PRDM16 mRNA content decreased in recovery from acute exercise, the present findings suggest that acute exercise elicits regulation of several brown adipose tissue genes in mouse WAT.