Evidence that human and equine erythrocytes could have significant roles in the transport and delivery of amino acids to organs and tissues.

Erythrocytes have a well-defined role in the gaseous exchange of oxygen and carbon dioxide in the mammalian body. The erythrocytes can contain more than half of the free amino acids present in whole blood. Based on measures showing that venous erythrocyte levels of amino acids are much less than arterial erythrocyte levels, it has previously been proposed that erythrocytes also play a role in the delivery of amino acids to tissues in the body. This role has been dismissed because it has been assumed that to act as an amino acid transport vehicle, the erythrocytes should release their entire amino acid content in the capillary beds at the target tissues with kinetic studies showing that this would take too long to achieve. This investigation set out to investigate whether the equine erythrocytes could rapidly take up and release smaller packages of amino acids when exposed to high or low external concentrations of amino acids, because it seemed very unlikely that cells would be able to release all of their amino acids without serious impacts on osmotic balance. Freshly prepared erythrocytes were placed in alternating solutions of high and low amino acid concentrations in PBS to assess the capacities of these cells to rapidly take up and release amino acids depending on the nature of the external environment. It was found that amino acids were rapidly taken up and released in small quantities in each cycle representing 15% of their total load in equine erythrocytes and 16% in human erythrocytes. The capacity for rapid uptake/release of amino acids by equine and human erythrocytes provided evidence to support the theory that mammalian erythrocytes have a significant role in transport of amino acids from the liver to tissues, muscles and organs.

A randomized trial to examine the mechanisms of cognitive, behavioral and mindfulness-based psychosocial treatments for chronic pain: Study protocol.

This randomized trial will evaluate the mechanisms of three chronic pain treatments: cognitive therapy (CT), mindfulness meditation (MM), and activation skills (AS). We will determine the extent to which late-treatment improvement in primary outcome (pain interference) is predicted by early-treatment changes in cognitive content, cognitive process, and/or activity level. The shared versus specific role of these mechanisms across the three treatments will be evaluated during treatment (Primary Aim), and immediately post-treatment to examine relapse mechanisms (Secondary Aim). We will enroll 300 individuals with chronic pain (with low back pain as a primary or secondary condition), with 240 projected to complete the study. Participants will be randomly assigned to eight, 1.5 h telehealth group sessions of CT, MM, or AS. Mechanisms and outcomes will be assessed twice daily during 2-week baseline, 4-week treatment period, and 4-week post-treatment epoch via random cue-elicited ecological momentary assessment (EMA); activity level will be monitored during these time epochs via daily monitoring with ActiGraph technology. The primary outcome will be measured by the PROMIS 5-item Pain Interference scale. Structural equation modeling (SEM) will be used to test the primary aims. This study is pre-registered on clinicaltrials.gov (Identifier: NCT03687762). This study will determine the temporal sequence of lagged mediation effects to evaluate rates of change in outcome as a function of change in mediators. The findings will provide an empirical basis for enhancing and streamlining psychosocial chronic pain interventions. Further, results will guide future efforts towards optimizing maintenance of gains to effectively reduce relapse risk.

Investigation of The Effects of Prosthetic Knee Condition for Individuals with Transfemoral Amputation During Attempted Running.

BACKGROUND: A number of individuals with unilateral transfemoral amputation (TFA) run in a prosthesis with an unlocked prosthetic knee, while others choose to run with a locked prosthetic knee to increase stability. Research regarding running with an unlocked knee (UK) versus a locked knee (LK), with respect to energy efficiency, is limited and might be enhanced by characterization of the impact of knee condition on kinematics. OBJECTIVES: To investigate the effect of an UK versus LK on hip kinematics, energy efficiency, and running speed. METHODOLOGY: Five male novice runners with unilateral TFA completed one three-minute self-selected running speed (SSRS) trial and three peak speed trials per knee condition. Hip kinematics, energy efficiency, and running speed were compared between conditions. FINDINGS: Four of the five subjects exhibited a fast walk, rather than a consistent run. Hip flexion increased for all subjects and hip abduction decreased for four subjects during swing phase for the UK condition. Hip kinematic asymmetry was reduced for the UK condition in the sagittal plane for four individuals; hip kinematic asymmetry was also reduced in the frontal plane for the UK condition for three of these individuals. Mean energy efficiency was better for the UK condition (UK: 0.282 mLO2/kg/m, LK: 0.328 mLO2/kg/m). Peak running speed did not differ significantly between knee conditions (UK: 1.47m/s, LK:1.32m/s). CONCLUSIONS: For novice recreational runners with unilateral transfemoral amputation, the UK condition resulted in improved energy efficiency and enhanced kinematic symmetry, despite comparable peak speed relative to the LK condition. Therefore the UK condition may be advantageous for mid-range distance running.

Modelling of protein turnover provides insight for metabolic demands on those specific amino acids utilised at disproportionately faster rates than other amino acids.

The nitrogen balance is regulated by factors such as diet, physical activity, age, pathogenic challenges, and climatic conditions. A paradigm was developed from published recommended rates of protein intake (g/kg/day) with corresponding rates of endogenous protein turnover and excretion, to extrapolate amino acid balances under various conditions. The average proportions of amino acids in the ingested proteins representing a well-balanced diet were used to assess intake and an average human composition profile from five major high-turnover proteins in the body to assess endogenous protein turnover. The amino acid excretion profiles for urine and sweat were constructed for males and females from published data. The model calculated the nitrogen balances for a range of amino acids to determine the amino acid requirements to support daily exertion. Histidine, serine, glycine, and ornithine were in negative balances in males and females and this potential deficit was greater in the higher body-mass ranges. Conversely, leucine, isoleucine, and valine were conserved during nitrogen flux and resulted in positive balances. The model was run under a scenario of high demand for the synthesis of IgG during a response to an infectious challenge which indicated that these were increased requirements for tyrosine, threonine, and valine. It was concluded that these amino acids represent points of limitation to anabolic metabolism by restriction of their supply at critical times of demand. This would especially occur under conditions of fitness training, maintaining intensive exercise regimes, facilitating responses to pathogenic challenge, or recovery from injury.

Pain referents used to respond to the pain catastrophizing scale.

BACKGROUND: Pain catastrophizing has emerged as a highly important construct in pain research. The Pain Catastrophizing Scale (PCS) is a widely used self-report measure used to determine a person's level of pain catastrophizing, assumed to be associated with an ongoing, recalled or anticipated pain experience. In practice, instructions for self-reporting catastrophizing typically do not provide a specific pain referent, even when assessing patients with chronic pain. Researchers have noted that it is not known what type of pain participants are referring to when responding to a catastrophizing questionnaire. METHOD: In the current study, 182 presumably healthy undergraduate students completed the PCS followed by a query regarding the pain referent used to complete the scale. In addition, they were asked if they have ever experienced chronic pain and to list their worst pain experience. RESULTS: The most commonly used primary referents included pain due to acute injury (26.4%), headache (18.0%) and general physical pain (11.5%). The type of primary referent and the number of referents did not influence the catastrophizing scores. However, the catastrophizing scores were influenced by the context of the primary pain referent, i.e., whether the primary pain referent was non-chronic worst pain, both chronic and worst pain, chronic pain or unrelated to either chronic or worst pain. Notably, a larger than expected proportion of participants reported having experienced chronic pain (44.5%; n = 81). CONCLUSION: The examination of pain referents while responding to a catastrophizing measure would add to our understanding of a person's pain experience and related catastrophic cognitions.

Analysis of electrical brain waves in neurotoxicology: γ-hydroxybutyrate.

Advances in computer technology have allowed quantification of the electroencephalogram (EEG) and expansion of quantitative EEG (qEEG) analysis in neurophysiology, as well as clinical neurology, with great success. Among the variety of techniques in this field, frequency (spectral) analysis using Fast Fourier Transforms (FFT) provides a sensitive tool for time-course studies of different compounds acting on particular neurotransmitter systems. Studies presented here include Electrocorticogram (ECoG) analysis following exposure to a glutamic acid analogue - domoic acid (DOM), psychoactive indole alkaloid - ibogaine, as well as cocaine and gamma-hydroxybutyrate (GHB). The ECoG was recorded in conscious rats via a tether and swivel system. The EEG signal frequency analysis revealed an association between slow-wave EEG activity delta and theta and the type of behavioral seizures following DOM administration. Analyses of power spectra obtained in rats exposed to cocaine alone or after pretreatment with ibogaine indicated the contribution of the serotonergic system in ibogaine mediated response to cocaine (increased power in alpha(1) band). Ibogaine also lowered the threshold for cocaine-induced electrographic seizures (increased power in the low-frequency bands, delta and theta). Daily intraperitoneal administration of cocaine for two weeks was associated with a reduction in slow-wave ECoG activity 24 hrs following the last injection when compared with controls. Similar decreased cortical activity in low-frequency bands observed in chronic cocaine users has been associated with reduced metabolic activity in the frontal cortex. The FFT analyses of power spectra relative to baseline indicated a significant energy increase over all except beta(2) frequency bands following exposure to 400 and 800 mg/kg GHB. The EEG alterations detected in rats following exposure to GHB resemble absence seizures observed in human petit mal epilepsy. Spectral analysis of the EEG signals combined with behavioral observations may prove to be a useful approach in studying chronic exposure to drugs of abuse and treatment of drug dependence.

Assessment of antioxidant nutrient intake of a population of southern US African-American and Caucasian women of various ages when compared to dietary reference intakes.

Antioxidant nutrient intervention strategies to ameliorate negative health factors are of notable research interest. Central to the thesis that antioxidant nutrients improve biological defense systems and provide health benefits is an accurate indication of daily antioxidant nutrient intake. Little information is available concerning these nutrient intakes among non-affluent women of the southern U.S. This study examines the 24-h intake of vitamins: A, E, C, -carotene, a-tocopherol, riboflavin, and minerals: zinc, selenium, copper, manganese, iron, and molybdenum among 259 Caucasian (CA) and African-American (AA) women from small urban communities. Women were non-pregnant females, 19-93 y of age. Statistical comparisons of nutrient intake were made by least squares means within age groups. Intakes were compared to various Dietary Reference Intakes including Recommended Daily Allowance (RDA) and Estimated Average Requirement (EAR) values as established by the U.S. National Research Council. Numerous dietary deficiencies in important antioxidant nutrients associated with metabolic antioxidant systems were identified. Few race-related differences were detected. Intake of vitamin A was generally within recommended levels while vitamin E intake was below the EAR. The vitamin precursors, -carotene and a-tocopherol, were significantly (P<0.05) below customary intakes at all ages. More than 60% of this population reported dietary copper, zinc, and selenium intakes below recommended levels. A lack of race differences for most nutrient intakes suggests similar socioeconomic or endogeneous regional factors. All women in this population reported dietary intakes of antioxidant vitamins and minerals below recommended values, conditions that could contribute to subsequent health risks unless nutrient-dense food choices and antioxidant supplementation are considered in their overall nutritional support.

Theoretical perspectives on the relation between catastrophizing and pain.

The tendency to "catastrophize" during painful stimulation contributes to more intense pain experience and increased emotional distress. Catastrophizing has been broadly conceived as an exaggerated negative "mental set" brought to bear during painful experiences. Although findings have been consistent in showing a relation between catastrophizing and pain, research in this area has proceeded in the relative absence of a guiding theoretical framework. This article reviews the literature on the relation between catastrophizing and pain and examines the relative strengths and limitations of different theoretical models that could be advanced to account for the pattern of available findings. The article evaluates the explanatory power of a schema activation model, an appraisal model, an attention model, and a communal coping model of pain perception. It is suggested that catastrophizing might best be viewed from the perspective of hierarchical levels of analysis, where social factors and social goals may play a role in the development and maintenance of catastrophizing, whereas appraisal-related processes may point to the mechanisms that link catastrophizing to pain experience. Directions for future research are suggested.

Application of electrophysiological method to study interactions between ibogaine and cocaine.

The psychoactive indole alkaloid, ibogaine (IBO), has been investigated for over a decade concerning its reported anti-addictive properties for opioids as well as psychomotor stimulants. The mechanism for the anti-addictive action of IBO is still unclear. IBO interactions with opioid, NMDA, nicotinic, adrenergic, and serotonergic receptor sites have been suggested. The involvement of the dopaminergic system in IBO action is well documented. Increased or decreased levels of dopamine (DA) in specific brain regions following IBO pretreatment have been seen concomitantly with increased or decreased motor activity after subsequent amphetamine or cocaine administration. In this report, in vivo electrophysiological measures were monitored in awake adult male rats in order to investigate alterations of the electrocorticogram (ECoG) resulting from interactions between IBO and cocaine (COC). Rats were implanted bilaterally with bipolar ECoG electrodes. They were either injected with saline, COC alone (20 mg/kg, i.p.) or IBO (50 mg/kg, i.p.) and COC 1 hr later. The concentrations of DA, 5-HT, and their metabolites DOPAC, HVA, and 5-HIAA were assessed in the caudate nucleus in separate groups of saline-, COC-, and IBO/COC-treated rats. An alpha1 power increase was observed within 10 min after COC injection, which lasted for less than 20 min. A desynchronization over alpha2 and both beta power bands was observed throughout the recording. In IBO/COC-treated rats, a significant increase in delta, theta, and alpha1 power occurred within 20 min after COC injection (p <0.05). This effect lasted for up to an hour. DA levels significantly increased after COC only and decreased after IBO administration. A further decrease in levels of DA was observed in IBO/COC-treated rats. DA turnover increased significantly after IBO alone but was not observed after IBO/COC treatment. The alterations in ECoG and neurotransmitter levels suggest a decreased response to COC following IBO pretreatment.

Bioassays of shortened duration for drugs: statistical implications.

Declining survival rates in rodent carcinogenesis bioassays have raised a concern that continuing the practice of terminating such studies at 24 months could result in too few live animals at termination for adequate pathological evaluation. One option for ensuring sufficient numbers of animals at the terminal sacrifice is to shorten the duration of the bioassay, but this approach is accompanied by a reduction in statistical power for detecting carcinogenic potential. The present study was conducted to evaluate the loss of power associated with early termination. Data from drug studies in rats were used to formulate biologically based dose-response models of carcinogenesis using the 2-stage clonal expansion model as a context. These dose-response models, which were chosen to represent 6 variations of the initiation-promotion-completion cancer model, were employed to generate a large number of representative bioassay data sets using Monte Carlo simulation techniques. For a variety of tumor dose-response trends, tumor lethality, and competing risk-survival rates, the power of age-adjusted statistical tests to assess the significance of carcinogenic potential was evaluated at 18 and 21 months, and compared to the power at the normal 24-month stopping time. The results showed that stopping at 18 months would reduce power to an unacceptable level for all 6 submodels of the 2-stage clonal expansion model, with the pure-promoter and pure-completer models being most adversely affected. For the 21-month stopping time, the results showed that, unless pure promotion can be ruled out a priori as a potential carcinogenic mode of action, the loss of power is too great to warrant early stopping.

The relation between pain beliefs, negative thoughts, and psychosocial functioning in chronic pain patients.

Cognitions and beliefs appear important in predicting adjustment to chronic pain. The current study examines how cognitions and beliefs are related to psychosocial functioning. One hundred and sixty-three chronic pain out-patients were assessed. Regression analyses were performed using scores on the Pain Beliefs and Perceptions Inventory and the Inventory of Negative Thoughts in Response to Pain as predictor variables and responses to the West Haven Yale Multidimensional Pain Inventory as criterion variables. Pain cognitions and pain beliefs were correlated. After controlling for demographics, employment status and pain severity, pain beliefs and cognitions accounted for a significant amount of the variance in general activity, pain interference, and affective distress. Negative cognitions, particularly negative self-statements, were more predictive of outcome than pain beliefs. Although these data are correlational, they provide additional support for a biopsychosocial model of adjustment to chronic pain.

The effect of pain on memory for affective words.

Memory is a key cognitive variable in pain management, but lacks extensive research. This study is a replication and extension of Seltzer and Yarczower's investigation of pain's influence on memory for affective words, which found fewer positive words and more negative words recalled if subjects were in acute pain (versus no pain). In the present study, two experiments were conducted: one with a recall memory test and one with a recognition memory test. One hundred sixty undergraduate subjects were randomly placed in one of four groups: two groups had the same condition (pain or no pain) for both the encoding task and memory test, and two groups had mixed conditions (pain at encoding-no pain at memory test or no pain at encoding-pain at memory test). Pain was induced by 0 degrees-2 degrees C water immersion. At encoding, subjects categorized words by judging them as either positive or negative. Results of both experiments show that pain impairs memory. In neither experiment were differences found on memory for positive and negative words. These results do not support Seltzer and Yarczower's discriminative effects of pain on word category, but they are consistent with other research using acute pain manipulations and chronic pain populations, suggesting that pain interferes with memory. It is hypothesized that pain depletes scarce attentional resources, thereby interfering with concurrent cognitive tasks such as thinking, reasoning, and remembering.

Alteration of electroencephalogram and monoamine concentrations in rat brain following ibogaine treatment.

Ibogaine (IBO) is a psychoactive indole alkaloid that has antiaddictive properties. However, treatment with IBO may lead to neurotoxicity, since IBO and its metabolites interact persistently with many neurotransmitter systems. Here, we recorded cortical electroencephalogram (EEG) signals from rats anesthetized with isoflurane. The heart rate (HR) was monitored via electrocardiogram (EKG) electrodes. After the baseline EEG was recorded, rats received one intraperitoneal (i.p.) dose of 50 mg/kg IBO. EEG signals were recorded for 2 hr. Rats were then sacrificed and brains dissected into frontal cortex (FC), caudate nucleus (CN), hippocampus (HIP), and brain stem (BS). The level of dopamine (DA), serotonin (5-HT), and their metabolites were determined by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). Compared with baseline, a decrease in HR immediately after IBO injection and a decrease in delta, theta, alpha and beta power spectra frequency bands (1-4, 4-8, 8-13, 13-32 Hz) during the first 30 min after IBO administration was observed. EEG recovered within the next 15 min. In CN, the level of DA decreased and DA turnover rate increased significantly. The levels of 5-HT increased in FC. The pattern of EKG AND EEG response to IBO may be due to multiple receptor interactions of IBO.

Assessment of ventricular volumes using cine magnetic resonance in the intact dog. A comparison of measurement methods.

UNLABELLED: RATIONALE, OBJECTIVE AND METHODS: The authors recently combined magnetic resonance imaging with high-fidelity left ventricular (LV) pressure measurement in a closed-chested, intact animal model. However, LV volumes derived from summated serial short axis slices require long imaging times and make it difficult to record LV volumes in response to acute alterations in load. In this study, geometry-based LV end-systolic volume estimates calculated from a single long-axis image (Area-Length formula) and from a long-axis and short-axis image (Bullet formula) were compared to those derived from summated short-axis images of the left ventricle (Simpson's rule) during altered loading conditions in six anesthetized, intact dogs. RESULTS: Angiotensin infusion produced three different LV systolic pressures (89 +/- 8 vs. 123 +/- 12 vs. 151 +/- 10 mmHg, P < .001). Area-Length and Bullet formula end-systolic volumes correlated with Simpson's rule volumes (r = .95 and .97; respectively). However, Bullet formula end-systolic volumes provided a significantly better agreement with Simpson's rule end-systolic volumes. CONCLUSIONS: The Bullet formula can be substituted for Simpson's rule to record magnetic resonance LV volumes during steady-state alterations in load in our intact animal model.

Sexual misconduct in psychotherapy: reactions to a consumer-oriented brochure.

Reactions of subjects to a brochure addressing the topic of sexual intimacy in psychotherapy was assessed. Fifty-four psychotherapy clients and 52 licensed psychologists responded favorably to the brochure, with the majority indicating that the brochure should be made available before therapy begins or during the first session. Potential clients (120 college students) read either the brochure on sexual misconduct or a control brochure containing general information about psychology. Subjects who read the sexual misconduct brochure showed increased ability to understand what is appropriate and inappropriate therapist behavior, see unwanted touch as nontherapeutic, regard a therapist talking a lot about his or her own sex life as inappropriate, view sex in the therapeutic relationship as inappropriate, and intend to behave assertively within the session if their therapist's behavior should make them feel uncomfortable. Subjects who read the control brochure showed no such changes.

Goals for coping with pain mitigate time distortion.

The cold pressor test was used to investigate the effect of specific versus nonspecific time-oriented goals on perception of time by a person experiencing pain. Headache pain has been shown to attenuate the retrospective estimates of time passage. In the present study, laboratory-induced (cold pressor) pain produced results congruent with those of a previous clinical report on headache. In addition, results indicated that giving a specific time goal for coping with pain minimized the time distortion. Time estimations of subjects in pain with a specified goal were found to be significantly longer (and more accurate) than time estimations of subjects who were in pain but not given a time-specific goal.

Time-varying wall stress: an index of ventricular vascular coupling.

Previous work in the isolated heart and intact circulation has suggested that the relationship between wall stress and time during left ventricular (LV) ejection is linear and that the slope, which will be referred to as time-varying wall stress, increases in response to augmentation in afterload. However, the etiology of the increase in slope has not been determined in an intact animal. Magnetic resonance imaging coupled with high-fidelity LV pressure measurement using a nonferrous catheter-tip manometer generates a detailed assessment of wall stress in an animal model where the thorax and pericardium have never been disturbed. Accordingly, six anesthetized dogs were studied during autonomic blockade with atropine and propranolol during angiotensin infusion, producing three widely disparate left ventricular systolic pressures (87 +/- 7 vs. 124 +/- 13 vs. 152 +/- 10 mmHg, P less than 0.001). Time-varying wall stress did not change from low to medium load (-42.4 +/- 9.5 to -27.3 +/- 22.3 g.cm-2.ms-1) but increased significantly at high load (-21.7 +/- 14.9 g.cm-2.ms-1, P less than 0.05). Analysis of the relative contribution of pressure, chamber radius, wall thickness, and long-axis dimension to the changes in time-varying wall stress demonstrated only the pressure component to change its relative contribution at medium (P less than 0.001) and high load (P less than 0.001). Therefore, we conclude that the increase in time-varying wall stress results from augmentation of pressure in the latter one-half of systole that is incompletely offset by shortening and wall thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

An "open-transformed scale" for correcting ceiling effects and enhancing retest reliability: the example of pain.

The use of closed scales (with anchors at each end) to measure pain was found to produce ceiling effects characterized by a deceleration of ratings toward the upper end of the scale. This was consistent with previous research. Apart from producing nonlinear functions, the closed scale also limited test-retest reliability because of subjects' tendencies to correct their distorted ratings in subsequent trials. However, an open-ended scale coupled with transformation of reported ratings into a decile scale virtually eliminated the ceiling effect, thus producing consistently linear functions and maximizing test-retest reliability. This finding may have implications for the measurement of other sensory and psychological phenomena, especially those in which the property evaluated varies in a continuous fashion.