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Statistical regularities and predictions can influence the earliest stages of visual processing. Studies examining their effects on detection, however, have yielded inconsistent results. In continuous flash suppression (CFS), where a static image projected to one eye is suppressed by a dynamic image presented to the other, the predictability of the suppressed signal may facilitate or delay detection. To identify the factors that differentiate these outcomes and dissociate the effects of expectation from those of behavioral relevance, we conducted three CFS experiments that addressed confounds related to the use of reaction time measures and complex images. In experiment 1, orientation recognition performance and visibility rates increased when a suppressed line segment completed a partial shape surrounding the CFS patch, demonstrating that valid configuration cues facilitate detection. In Experiment 2, however, predictive cues marginally affected visibility and did not modulate localization performance, challenging existing findings. In experiment 3, a relevance manipulation was introduced; participants pressed a key upon detecting lines of a particular orientation, ignoring the other possible orientation. Visibility and localization were enhanced for relevant orientations. Predictive cues modulated visibility, orientation recognition sensitivity, and response latencies, but not localization-an objective measure sensitive to partial breakthrough. Thus, while a consistent surround can strongly enhance detection during passive observation, predictive cueing primarily affects post-detection factors such as response readiness and recognition confidence. Relevance and predictability did not interact, suggesting that the contributions of these two processes to detection are mostly orthogonal., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A cognitive system faced with contingent events that cause rapid changes in sensory data may (i) incrementally incorporate new data into the ongoing perceptual and motor processing; or (ii) restart processing on each new event; or (iii) sample the data and hold onto the sample until its processing is complete, while disregarding any contingent changes. We offer a set of computational first-principles arguments for a hypothesis, according to which any system that contends with certain classes of perception and behavioral control tasks must include the sample-and-hold option (possibly alongside the other two, which may be useful in other tasks). This hypothesis has implications for understanding the dynamics of perception and action. In particular, a sample-and-hold channel necessarily processes sensory data on some kind of cycle (which does not imply precise periodicity). Further, being prepared to face the world at all times requires that the sampling that initiates each cycle be triggered by every significant action on part of the agent itself, such as saccades. We survey a range of evidence for the sample-and-hold functionality, touching upon diverse phenomena such as attentional blink and backward masking, the yoking of olfaction to respiration, thalamocortical interactions, and metastable brain dynamics in perception and consciousness., (© 2017 Elsevier B.V. All rights reserved.)

MicroRNAs (miRNA) are central regulators of diverse biological processes and are important in the regulation of stem cell self-renewal. One of the widely studied miRNA-protein regulators is the Lin28-Let-7 pair. In this study, we demonstrate that contrary to the well-established models of mouse ES cells (mESC) and transformed human cancer cells, the pluripotent state of human ES cells (hESC) involves expression of mature Let-7 family miRNAs with concurrent expression of all LIN28 proteins. We show that mature Let-7 miRNAs are regulated during hESC differentiation and have opposite expression profile with LIN28B. Moreover, mature Let-7 miRNAs fine tune the expression levels of LIN28B protein in pluripotent hESCs, whereas silencing of LIN28 proteins have no effect on mature Let-7 levels. These results bring novel information to the highly complex network of human pluripotency and suggest that maintenance of hESC pluripotency differs greatly from the mESCs in regard to LIN28-Let-7 regulation., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Conflicting clinical evidence regarding the possible association between androgen deprivation therapy (ADT) with heart failure in men with prostate cancer is reviewed, including 2 population-based registries showing such an association, and 1 showing no association. Studies of the effects of androgens on cardiomyocyte contractility at the molecular level, the effects of testosterone on the cardiovascular system, particularly cardiac function, and the beneficial effects of testosterone therapy for patients with heart failure might help illuminate this controversy. Future studies are needed to evaluate the effect of ADT on end points of heart failure. The authors weigh the possible adverse effects of ADT on cardiac function and heart failure against its known benefits to cancer outcomes, defined according to published, randomized trials, in a discussion of the implications of the preclinical and clinical literature on the management of prostate cancer in men at risk for heart failure. In the absence of conclusive evidence that ADT causes heart failure, the authors discuss clinical situations in which ADT may be delayed, given on a short-term or intermittent basis, or withheld from treatment with the goal of reducing the risks of heart failure without compromising prostate cancer outcomes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Prepulse inhibition (PPI) of the startle response is a cross-species measure of sensorimotor gating that provides a valuable tool for assessing the capacity to effectively screen out irrelevant sensory input. Accumulating evidence suggests that PPI deficits may correlate with impairments in social cognition, i.e. the ability to construct representation about others, oneself and the relations between others and oneself. Social cognition deficits are commonly encountered within the framework of psychiatric disorders. In this study 113 healthy volunteers completed psychopyhsiological measures of sensorimotor gating (PPI) and social self-presentation style (the Concern for Appropriate (CAS) and the Revised Self-Monitoring (RSMS) scales). CAS measures a defensive and fearful social approach aiming at avoiding social threats; RSMS measures an active and flexible social approach aiming at gaining power and status. Analyses revealed an inverse correlation between PPI at the 120 ms prepulse-to-pulse interval and total CAS scores (r=-0.19, p=0.04), as well as with the Attention to Social Comparison Information (ASCI) subscale of the CAS (r=-0.23, p=0.01). These findings suggest that reduced PPI may contribute to the tendency to adopt a defensive and fearful "getting along" social approach. This study is, to our knowledge, the first to assess the relationship between sensorimotor gating and self-presentational style in humans. Its findings suggest that very basic perceptual deficits that can be assessed using the PPI paradigm, may reflect information processing abnormalities that impact negatively upon the perception of complex social interactions., (Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.)

Variation set structure--partial overlap of successive utterances in child-directed speech--has been shown to correlate with progress in children's acquisition of syntax. We demonstrate the benefits of variation set structure directly: in miniature artificial languages, arranging a certain proportion of utterances in a training corpus in variation sets facilitated word and phrase constituent learning in adults. Our findings have implications for understanding the mechanisms of L1 acquisition by children, and for the development of more efficient algorithms for automatic language acquisition, as well as better methods for L2 instruction.

There is a growing consensus that blood glucose control, and postprandial control in particular, must become more aggressive if we are to stem the growing tide of diabetes-related complications and mortality. For most patients, this means that insulin therapy must begin earlier and that insulin must be titrated sufficiently to achieve tighter glycemic targets. The limitations of traditional treatment regimens, delivery devices and conventional insulin formulations, in conjunction with patient factors, have prevented the majority of people with type-2 diabetes from realizing the potential benefits of insulin therapy and achieving recommended glycemic targets. Fortunately, modern insulin analog formulations, new treatment regimens, and advanced delivery devices are now available. This review will discuss features of these new tools, and compare the benefits of using premixed insulin versus a basal-only approach to initiating insulin therapy. Once physicians become familiar with these tools and incorporate them into daily practice, they will be able to better tailor diabetes self-management programs to the needs of individual patients. The result will be that more patients should be able to reach recommended glycemic targets with greater convenience and safety than has previously been available.

GafD in Escherichia coli G (F17) fimbriae is associated with diarrheal disease, and the structure of the ligand-binding domain, GafD1-178, has been determined at 1.7A resolution in the presence of the receptor sugar N-acetyl-D-glucosamine. The overall fold is a beta-barrel jelly-roll fold. The ligand-binding site was identified and localized to the side of the molecule. Receptor binding is mediated by side-chain as well main-chain interactions. Ala43-Asn44, Ser116-Thr117 form the sugar acetamide specificity pocket, while Asp88 confers tight binding and Trp109 appears to position the ligand. There is a disulfide bond that rigidifies the acetamide specificity pocket. The three fimbrial lectins, GafD, FimH and PapG share similar beta-barrel folds but display different ligand-binding regions and disulfide-bond patterns. We suggest an evolutionary path for the evolution of the very diverse fimbrial lectins from a common ancestral fold.

Type 2 diabetes is a common disorder often accompanied by numerous metabolic abnormalities leading to a high risk of cardiovascular morbidity and mortality. Results from the UKPDS have confirmed that intensive glucose control delays the onset and retards the progression of microvascular disease and possibly of macrovascular disease in patients with type 2 diabetes. In the early stages of the disease, insulin resistance plays a major role in the development of hyperglycemia and other metabolic abnormalities, and patients with type 2 diabetes often benefit from measures to improve insulin sensitivity such as weight loss, dietary changes, and exercise. Later, the use of oral insulin secretagogues and insulin sensitizers as monotherapy and in combination helps maintain glycemia for varying periods of time. Ultimately, because of the progressive nature of the disease and the progressive decline in pancreatic beta-cell function, insulin therapy is almost always obligatory to achieve optimal glycemic goals. Not all patients are candidates for aggressive insulin management; therefore, the goals of therapy should be modified, especially in elderly individuals and those with co-morbid conditions. Candidates for intensive management should be motivated, compliant, and educable, without other major medical conditions and physical limitations that would preclude accurate and reliable HGM and insulin administration. In selected patients, combination therapy with insulin and oral antidiabetic medications can be an effective method for normalizing glycemia without the need for rigorous multiple-injection regimens. The patients for whom combination therapy is most commonly successful are those who do not achieve adequate glycemic control using daytime oral agents but who still show some evidence of responsiveness to the medications. Bedtime intermediate-acting or predinner premixed intermediate- and rapid-acting insulin is administered and progressively increased until the FPG concentration is normalized. If combination therapy is not successful, a split-mixed regimen of intermediate- and rapid-acting insulin equally divided between the prebreakfast and pre-dinner periods is advised for oese patients, and more intensive regimens are advised for thin patients. Insulin therapy is invariably associated with weight gain and hypoglycemia. The use of metformin or glitazones in combination with insulin has been demonstrated to have insulin-sparing properties. Also, metformin use may ameliorate weight gain. The use of continuous subcutaneous insulin infusion pumps can be particularly beneficial in treating patients with type 2 diabetes mellitus who do not respond satisfactorily to more conventional treatment strategies. Intraperitoneal insulin delivery systems hold considerable promise in type 2 diabetes because of their more physiologic delivery of insulin and their ability to inhibit hepatic glucose production selectively, with less peripheral insulinemia than with subcutaneous insulin injections. Newer insulin analogues such as the rapidly acting Lispro insulin and the peakless, long-acting glargine insulin are increasingly being used because of their unique physiologic pharmacokinetics. New developments such as inhaled and buccal insulin preparations will also make it easier for many patients to initiate and maintain a proper insulin regimen. Finally, a new generation of gut peptides such as amylin and GLP-1 will add a new dimension to glycemic control through modification of nutrient delivery and other mechanisms; however, the ultimate goal in the management of type 2 diabetes is the primary prevention of the disease. The Diabetes Prevention Program (DPP) sponsored by the National Institutes of Health has currently randomly assigned more than 3000 persons with impaired glucose tolerance and at high risk of developing diabetes into three treatment arms: metformin arm, an intensive lifestyle-modification arm, and a placebo arm. The study will conclude in 2002 after all participants have been followed for 3 to 6 years.

To facilitate timely application of new forms of cardiac support to patients at highest risk after cardiotomy despite conventional support with the intraaortic balloon pump, an accurate prediction of survival must be available at the time of weaning from cardiopulmonary bypass. We, therefore, acquired 240 demographic, disease, and perioperative characteristics of 322 patients (mortality rate, 48.4%) who required IABP support to separate from bypass. Four variables available before or within 10 minutes of the first attempt at weaning from bypass significantly predicted mortality by stepwise logistic regression: complete heart block as demonstrated by need for temporary pacing at weaning (p < 0.001), advanced age (p < 0.002), preoperative blood urea nitrogen concentration (p = 0.036), and female sex (p = 0.048). An equation generated by the logistic model predicted a 72.2% survival rate in the 25% of patients at least risk (actual survival rate, 71.6%); in the 25% at greatest risk, death was predicted in 73.0%, and the actual mortality rate was 74.1%. The equation was then prospectively applied to 330 intraaortic balloon pump-supported patients managed at another institution. The overall mortality rate there was 41.2%; in the 25% at least risk, predicted survival rate was 70.5% (actual survival rate, 77.1%), and in the 25% at greatest risk, predicted mortality rate was 75.7% (actual mortality rate, 62.7%). Thus, retrospectively at one institution and prospectively at another, the equation generated by this model based only on data available at the time of weaning from bypass was able to define one subgroup of patients 2.6 to 2.7 times as likely to die as another subgroup from within similar cohorts.(ABSTRACT TRUNCATED AT 250 WORDS)

In this study, we compared the procedure-related complications of inpatient and outpatient cardiac catheterization when performed at the same institution by the same group of cardiologists. The majority of the studies were done using a brachial arterial cutdown approach. The mean age, sex, cardiac diagnosis, mean left ventricular ejection fraction, and the distribution of coronary arterial lesions were similar in both groups. There were relatively more patients in the New York Heart Association's class 4 in the inpatient group (p less than 0.01). In the outpatient group (676 patients), there were no major complications, and the rate of minor complications was 1 percent. In the inpatient group (1,106 patients), the rate of major complications was 0.4 percent and of minor complications 1.4 percent. The rates of major, minor, and total complications were statistically similar between the two groups. In the outpatient group the presence of left main coronary arterial disease, triple-vessel coronary disease, a left ventricular ejection fraction less than 30 percent, or a history of a recent myocardial infarction did not alter rates of complications. The hospital-related cost of the procedure on an outpatient basis was 26 percent less than on an inpatient basis. Our findings indicate that outpatient cardiac catheterization, using a brachial cutdown approach, is safe even in a higher risk subgroup of patients and provides significant financial savings.

NADH-cytochrome b5 reductase is the predominant NADH-diaphorase found in the human neutrophil (Blood 62:152, 1983). Although this reductase segregates with the light membranes of nitrogen-cavitated neutrophils separated on Percoll gradients (which include the plasma membrane markers alkaline phosphatase and NADPH-oxidase), it is approximately 95% excluded from plasma membrane-enriched phagocytic vacuoles. The reductase constitutes approximately 5% of the light membrane fraction FAD-flavoprotein (14.8 +/- 5.5 pmol/mg protein) and was found in equimolar concentration with a high potential b cytochrome also present in this light membrane fraction and tentatively identified as cytochrome b5. Isolation of the reductase from human neutrophils was accomplished by Triton X-114 solubilization of the light Percoll gradient membranes, followed by temperature-dependent phase separation and then affinity chromatography on AMP-Sepharose. The active preparation contained 1.3 mol FAD/mol protein, migrated on sodium dodecyl sulfate-polyacrylamide gels as a single band corresponding to an apparent mol wt of 45,000 daltons, exhibited a pl of 5.7 on chromatofocusing and was obtained in greater than 70% yield, with an overall purification of almost 900-fold. The purified enzyme was characterized by a high specificity for NADH as electron donor (Km = 6.4 mumol/L v Km greater than 1.6 mmol/L for NADPH) and exhibited a maximal turnover of ca. 30,000 min-1 at 22 degrees C with either ferricyanide or cytochrome b5 (Km = 10 nmol/L) as electron acceptor. Although the physical characterization and biochemical properties described here demonstrate that this neutrophil NADH b5 reductase is similar to the corresponding liver and erythrocyte enzymes, its unique function in the neutrophil has yet to be determined.