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The acid-base chemistry that drives catalysis in pyridoxal-5'-phosphate (PLP)-dependent enzymes has been the subject of intense interest and investigation since the initial identification of PLP's role as a coenzyme in this extensive class of enzymes. It was first proposed over 50 years ago that the initial step in the catalytic cycle is facilitated by a protonated Schiff base form of the holoenzyme in which the linking lysine ε-imine nitrogen, which covalently binds the coenzyme, is protonated. Here we provide the first (15)N NMR chemical shift measurements of such a Schiff base linkage in the resting holoenzyme form, the internal aldimine state of tryptophan synthase. Double-resonance experiments confirm the assignment of the Schiff base nitrogen, and additional (13)C, (15)N, and (31)P chemical shift measurements of sites on the PLP coenzyme allow a detailed model of coenzyme protonation states to be established.

Weather and climate extremes profoundly affect society and the environment, resulting in the loss of life, property, and habitat. The extremes discussed herein are causally related: extratropical storms account for the majority of extreme winds during the cold season, and extreme waves are largely driven by extreme winds. For assessment purposes, extremes are defined based on meteorological principles rather than physical destructiveness. Nevertheless, each of these extremes can result in substantial societal impacts. Estimates of extratropical storm activity primarily derive from two sources: atmospheric reanalyses and pressure-based indices. Reanalysis products have the advantage of uniform space and time fields on which to locate pressure minima or vorticity maxima, facilitating the identification of storm tracks. In contrast, pressure-based indices have the advantage of being directly computed from in situ observations, which often extend further back in time than most reanalyses.

Nicotine has been reported to produce both anxiolytic and/or anxiogenic effects in humans and animals.This study examined whether pretreatment with nicotine would alter anxiety in a unique runway model of approach–avoidance conflict.Food-restricted rats were trained to run a straight alley once a day to obtain food upon goal-box entry. Beginning on trial 11, food reward was followed by a series of five foot shocks (0.3–0.4 mA, 0.5 s) in the goal box. Non-shocked control rats continued to run for food only. The resulting association of the goal box with both a positive (food) and negative (foot shock) stimulus produced an approach–avoidance conflict (subjects exhibited “retreat behaviors” in which they would approach the goal box, stop, and then retreat back towards the start box). Once retreats were established, their sensitivity to nicotine pretreatment (0.0, 0.03, 0.045, 0.06, or 0.075 mg/kg, i.v.) was compared to saline. In subsequent tests, the effects of nicotine (0.06 or 0.03 mg/kg) were examined on spontaneous activity (locomotion) and center-square entries in an open field (anxiety).Doses of 0.06 and 0.075 mg/kg, but not lower doses of nicotine, reduced the number of runway retreats, and 0.06 mg/kg nicotine increased the number of open-field center entries relative to saline. No effects on locomotion were observed.Nicotine reduced approach–avoidance conflict and increased the rats’ willingness to enter the center of an open field, suggesting that the drug can produce anxiolytic properties and that such effects may serve as an important factor in the persistence of smoking behavior.

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A report on head trauma using the 2014 National Readmission Database described a significant readmission rate of 8.9%. This study was undertaken to reevaluate the rate based on more granular ICD10 codes and to identify any factors associated with readmission that may be targeted to reduce readmission. Patients were identified from the 2019 National Readmission Database with an ICD10 code for head trauma. Readmission was defined as occurring within 30 days of initial hospital admission. Comparisons were made using chi square, Mann Whitney rank sum, or multivariable logistic regression. The readmission rate was 5.0%. The rate was higher among men (5.6% vs 4.3%, P < 0.001) and patients ≥65 years of age (5.8% vs 3.9%, P < 0.001). Multiple injuries, discharge against medical advice, and government insurance were associated with higher rates. The mortality rate among those readmitted was 4.34%. Among patients readmitted, the most common primary nontrauma diagnoses were seizure disorder (7.7%) and cerebrovascular disease (3.4%). Younger patients had a higher rate of readmission for seizures (10.3% vs 6.1%, P < 0.001) and a lower rate of cerebrovascular disease (2.3% vs 6.4%, P = 0.004). The readmission rate was lower than previously described. Quality metrics used by hospitals should use the revised numbers. Based on the data, we suggest possible interventions to reduce readmission, including a trial among younger men of empirical antiepileptic medications and of prophylactic or continued antibiotics among elderly patients. These interventions should be evaluated to determine if they could reduce readmission, particularly among patients who leave against medical advice. [ABSTRACT FROM AUTHOR]

The training of animals is an ancient anthropogenic process; however, it was not until the birth of comparative psychology, as a science, that the mysterious ways of the animal trainer were formally explained. In this review I will discuss the contributions of comparative psychology both past and present in animal training. The discoveries of comparative psychologists have greatly enhanced the animal training process and resulted in new methods for training animals; for example, training animals using social models. Despite, comparative psychology being a quantitative science we have still to empirically evaluate the animal training process. I therefore suggest how we might further our understanding of animal training and hence animal learning processes through the collection of data and meta-analyses.Training in the circus world (as well as outside it) is surrounded with secrets, mystic and magic. Trainers seem almost frightened that their secrets will out...Kiley-Worthington, 1990, p. 140.

INTRODUCTIONNative Americans have been subjected to colonial domination by European nations for five centuries, resulting in a radical destabilization of their sociocultural and economic systems, a general deterioration of health, and rapid depopulation. The resulting effects of cultural differences and conflicts, learned dependency, poverty, and feelings of powerlessness and low self-regard have impacted dramatically the health and quality of Native life. American Indians in the United States today are facing major health and social problems such as diabetes, substance abuse, poor nutrition, obesity, vehicular accidents, and suicides. Alcohol abuse, for example, is implicated in four of the ten leading causes of death among Native Americans. Entire communities are crippled by health problems, which ultimately feed into a cycle of despair, cultural dislocation, and lack of self-sufficiency.This article explores how participants in a self-empowerment program have understood and translated the training into self-sufficiency both at the personal and community levels. In analyzing this process we will listen to the participants’ voices, the words and the meanings they give to what they have learned from the program, and what enabled them to do something for themselves and others.

Importance: Current eligibility criteria for lung cancer (LC) screening are derived from randomised controlled trials and primarily based on age and smoking history. However, the individual benefits of screening are highly variable and potentially attenuated by co-morbidities such as advanced airflow limitation (AL).Objective: To examine the relationship between the presence and severity of AL and screening outcomes.Methods: This was a secondary analysis of 18 463 high-risk smokers, a substudy from the National Lung Screening Trial, who underwent pre-bronchodilator spirometry at baseline and median follow-up of 6.1 years. We used descriptive statistics and a competing risk proportional hazards model to examine differences in screening outcomes by chronic obstructive pulmonary disease severity group.Results: The risk of developing LC increased with worsening AL (effect size=0.34, p<0.0001), as did the risk of dying of LC (effect size=0.35, p<0.0001). While those with severe AL (Global Initiative for Obstructive Lung Disease, GOLD grade 3-4) had the highest risk of LC and the highest LC mortality, they also had fewer adenocarcinomas (effect size=-0.20, p=0.008) and a lower surgery rate (effect size=-0.16, p=0.014) despite comparable staging, and greater non-LC mortality relative to LC mortality (effect size=0.30, p<0.0001). In participants with no AL, screening with CT was associated with a significant reduction in LC deaths relative to chest X-ray (30.3%, 95% CI 4.5% to 49.2%, p<0.05). The clinically relevant but attenuated reduction in those with AL (18.5%, 95% CI -8.4% to 38.7%, p>0.05) could be attributed to GOLD 3-4, where no appreciable mortality reduction was observed.Conclusion: Despite a greater risk of LC, severe AL was not associated with any apparent reduction in LC mortality following screening. [ABSTRACT FROM AUTHOR]

The purpose of this study is to examine the perceptions of online master's students regarding their best learning experiences. The authors surveyed 86 graduate students concerning what helped them learn in the online environment. Results indicate that although graduate students learned using the same technological tools as undergraduates, they desired a deeper level of learning that requires more instructional forethought and planning. Student experiences were consistent with the constructivist theory, and implications for improving teaching based upon the constructivist theory are highlighted.