Intra- and intermolecular effects on the Compton profile of the ionic liquid 1,3-dimethylimidazolium chloride.

We present a comprehensive simulation study on the solid-liquid phase transition of the ionic liquid 1,3-dimethylimidazolium chloride in terms of the changes in the atomic structure and their effect on the Compton profile. The structures were obtained by using ab initio molecular dynamics simulations. Chosen radial distribution functions of the liquid structure are presented and found generally to be in good agreement with previous ab initio molecular dynamics and neutron scattering studies. The main contributions to the predicted difference Compton profile are found to arise from intermolecular changes in the phase transition. This prediction can be used for interpreting future experiments.

Reproducibility of a task description questionnaire for working pregnant women.

The objective of this study was to evaluate the reproducibility of a Task Description Questionnaire that was designed to investigate exposures to, and influential factors for, problematic tasks experienced by working pregnant women. The questionnaire comprised questions concerning 22 task components (covering working posture, manual material handling, work pace, prolonged postures and others), eight influential factors contributing to problematic tasks, discomfort (measured using a body map) and level of effort to perform the tasks. Reproducibility of the questionnaire was assessed by interviewing participants on two occasions one week apart for interviews at both 20 and 34 weeks of pregnancy. Eleven and 13 problematic tasks were reported by 21 working pregnant women at 20 and 34 weeks of pregnancy, respectively. These tasks were surveyed using the Task Description Questionnaire. Kappa statistics and correlation coefficients (supplemented by paired t-tests) were used to examine the reproducibility of responses to the questionnaire. The results showed that most of the variables were measured with very good or satisfactory reproducibility. The reproducibility of exposure to work posture was higher than that of exposure to manual material handling. There was no significant difference between test and retest means for the discomfort scores measured on the body map, except for the maximum discomfort score for the whole body in the 34 weeks survey. The study suggests that the questionnaire can be reliably used in the study of problematic tasks experienced by pregnant women. But an initial preview of the questions by the subjects and explanation of the questions given to the subjects by the interviewer may help to produce more reliable results.

Viscous water meniscus under nanoconfinement.

A dramatic transition in the mechanical properties of water is observed at the nanometer scale. For a water meniscus formed between two hydrophilic surfaces in the attractive region, with < or = 1 nm interfacial separation, the measured viscosity is 7 orders of magnitude greater than that of bulk water at room temperature. Grand canonical Monte Carlo simulations reveal enhancement in the tetrahedral structure and in the number of hydrogen bonds to the surfaces as a source for the high viscosity; this results from a cooperative effect of hydrogen bonding of water molecules to both hydrophilic surfaces.

Analysis of self-reported problematic tasks for pregnant women.

The objective of this study was to identify major components of, and influential factors in, problematic tasks performed by pregnant women employed in education, health care and service areas. Seventy-two pregnant women were surveyed using specially designed questionnaires consisting of an Initial Survey, a Job Analysis Questionnaire and a Task Description Questionnaire. Forty-four subjects (60%) had difficulty performing at least one work task and reported 105 tasks that were problematic at work. Reaching above the head, bending forward, bending and twisting, pushing, repeating actions and working at a fast pace were identified as the task components requiring the greatest level of effort. Excessive effort, excessive time, getting tired, repetitive actions, stress and fear of injury were identified as factors that had strong associations with the six major task components. Findings of this study suggest that these task components and factors should be considered when designing, assigning or analysing tasks for working pregnant women.

Effects of human pregnancy on cardiac autonomic function above and below the ventilatory threshold.

This study examined the effects of human pregnancy on heart rate variability (HRV), spontaneous baroreflex (SBR) sensitivity, and plasma catecholamines at rest and during exercise. Subjects were 14 healthy, physically active pregnant women (PG; mean gestational age = 33.9 +/- 1.0 wk). Results were compared with an age-matched nonpregnant control group (NPG; n = 14) with similar characteristics. The electrocardiographic R-wave-R-wave interval and systolic blood pressure (via finger plethysmograph) were measured on a beat-to-beat basis at rest and during upright cycling at 60 and 110% of the ventilatory threshold (T(vent)). Parasympathetic nervous system (PNS) modulation (as reflected by HRV high-frequency/total power and SBR slope) was significantly reduced at rest in the PG vs. the NPG. During exercise, PNS modulation decreased significantly in both groups, but the magnitude of PNS withdrawal from rest to 110% T(vent) was smaller in the PG vs. NPG. Sympathetic nervous system (SNS) modulation (reflected by the low-frequency power-to-high-frequency power ratio) increased above resting values at 60 and 110% T(vent) in the NPG. SNS modulation at 110% T(vent) was significantly lower in the PG compared with the NPG. Plasma norepinephrine and epinephrine levels were also lower at 110% T(vent) in the PG. It was concluded that healthy pregnant women exhibit lower PNS modulation at rest and blunted SNS modulation during exercise above T(vent) in late gestation.

Role of LIM domains in mediating signaling protein interactions.

LIM domains are double zinc-finger motifs that mediate protein interactions between transcription factors, cytoskeletal and signaling proteins. This review outlines the protein interactions mediated by LIM domains with signaling proteins including tyrosine and serine/threonine kinases and phosphatases.

Glutamatergic drugs exacerbate symptomatic behavior in a transgenic model of comorbid Tourette's syndrome and obsessive-compulsive disorder.

We previously created a transgenic mouse model of comorbid Tourette's syndrome and obsessive-compulsive disorder (TS+OCD), by expressing a neuropotentiating cholera toxin (CT) transgene in a subset of dopamine D1 receptor-expressing (D1+) neurons thought to induce cortical and amygdalar glutamate output. To test glutamate's role in the TS+OCD-like disorder of these transgenic mice (D1CT-7 line), the effects of glutamate receptor-binding drugs on their behavior were examined. MK-801, a non-competitive NMDA receptor antagonist that indirectly stimulates cortical-limbic glutamate output, aggravated a transgene-dependent abnormal behavior (repetitive climbing and leaping) in the D1CT-7 mice at doses insufficient to induce stereotypies, and more readily induced stereotypies and limbic seizure behaviors at high doses. NBQX, a seizure-inhibiting AMPA receptor antagonist, reduced only the MK-801-dependent stereotypic and limbic seizure behavior of D1CT-7 mice, but not their transgene-dependent behaviors. These data imply that TS+OCD-like behavior is mediated by cortical-limbic glutamate, but that AMPA glutamate receptors are not an essential part of this behavioral circuit. Our findings lead to the prediction that the symptoms of human Tourette's syndrome and obsessive-compulsive disorder are elicited by excessive forebrain glutamate output.

TS+OCD-like neuropotentiated mice are supersensitive to seizure induction.

Seizures can be induced by systemic dopamine D1 receptor agonists or by cortical-limbic neurostimulation non-selectively. Seizures are also often associated with tics and compulsions, which likewise involve cortical-limbic hyperactivity. To determine if selective potentiation of cortical-limbic D1 receptor-expressing (D1+) neurons increases seizure susceptibility, we administered pentylenetetrazole (PTZ) to mice that express a neuropotentiating transgene only in a glutamatergic, cortical-limbic subset of D1+ neurons (D1CT-7 line). These mice exhibited increased PTZ-dependent seizure incidence, onset rate and intensity. Because D1CT-7 mice also exhibit tic+compulsion-like behaviors, this implies that glutamatergic hyperactivity induced by cortical-limbic D1+ neuropotentiation facilitates not only epilepsy but also tics and compulsions. This suggests a dopamine-regulated glutamatergic basis for all three states and may explain why they often co-exist in humans.

Differing attitudes between psychiatrists and primary care providers at the interface.

OBJECTIVE: Market forces caused by managed care are shaping practice styles for both psychiatrists and primary care physicians. This study offers a sample of the attitudes of both groups of practitioners highlighting the differences. METHOD: Forty-two psychiatrists and primary care physicians (PCP) completed surveys. The responses of each group were compared using chi square analyses. RESULTS: Psychiatrists and PCPs differed significantly on their: 1) degree of comfort in the other's traditional service domain--with PCPs more comfortable dealing with their patients' psychiatric problems than psychiatrists were dealing with their patients' medical problems, 2) perceived barriers to effective communication-psychiatrists acknowledge their own time constraints while PCPs blame their colleagues unavailability (actually an agreement that psychiatrists' availability is a limiting factor), 3) projected areas of interface in the future--with psychiatrists prioritizing collaboration on health maintenance while PCPs valued collaboration on prevention and referral as equally significant. CONCLUSIONS: Conflict between needs and expectations found in this pilot study, if shown in larger studies to be representative, will impact the success of changes in practice patterns encouraged by emerging managed care initiatives. These findings suggest that the discordant expectations between psychiatrists and PCPs about the interface of their practices deserve further study.

Effects of pregnancy and chronic exercise on maternal cardiac structure and function.

This study examined the interactive effects of pregnancy and aerobic conditioning on maternal cardiac structure and function. Effects of closely monitored cycle ergometer conditioning were studied during the second (TM2) and third trimesters (TM3) in 22 previously sedentary pregnant women (exercised group, EG) and a nonexercising pregnant control group with similar characteristics (CG, n = 19). Subjects were studied in the resting state by two-dimensional echocardiography and during cycle ergometer exercise at three steady-state power outputs at the start of TM2 (ENTRY), at the end of TM2 and TM3 (postconditioning), and 3-4 months postpartum (NPR, nonpregnant reference, CG only). Aerobic conditioning did not increase left ventricular dimensions beyond those attributable to pregnancy itself. In addition, in contrast with previous studies of nonpregnant women, physical conditioning during pregnancy did not reduce heart rate (HR) in the resting state. During exercise, the slope of the HR versus oxygen uptake (VO2) regression decreased significantly between preconditioning and the end of TM3 in the EG, suggesting that training-induced reductions in HR become more evident with increasing exercise intensity. Also, significant reductions in oxygen pulse (VO2/HR) were observed at all three work rates in the CG, but not in the EG. These findings support the hypothesis that the cardiovascular effects of aerobic conditioning are obscured by more powerful effects of pregnancy in the resting state but become "unmasked" during strenuous exercise.

Socio-demographic variations in perspectives on cardiovascular disease and associated risk factors.

Coronary heart disease (CHD) rates in Ireland are very high but little is known about attitudes to the disease. Qualitative attitudinal data were collected in focus group settings from 74 individuals across socio-demographic categories in order to assess knowledge of and attitudes to CHD and associated risk factors. Focus group questions were derived from group deconstruction of constructs from the Health Belief Model, Theory of Planned Behaviour, Protection Motivation Theory and Social Learning Theory. Participants were drawn from the personnel lists of local government and a health authority hospital. Eight types of groups were constructed according to the various permutations of the three variables: age, gender and occupational group. Analyses revealed good knowledge levels about risk factors among participants. However, participants exhibited mixed loci of control and low motivation to change behaviours. Men generally were less motivated to change than women; older men thought it too late and younger ones too soon. Though white and blue collar groups' views were similar, the discussion in white collar groups was more varied. Participants were sceptical about apparently contradictory medical advice which undermined motivation to change. The data complement earlier work and suggest preventative initiatives should be more focused.

Characterization of two isoforms of the skeletal muscle LIM protein 1, SLIM1. Localization of SLIM1 at focal adhesions and the isoform slimmer in the nucleus of myoblasts and cytoplasm of myotubes suggests distinct roles in the cytoskeleton and in nuclear-cytoplasmic communication.

We have cloned and characterized a novel isoform of the skeletal muscle LIM protein 1 (SLIM1), designated SLIMMER. SLIM1 contains an N-terminal single zinc finger followed by four LIM domains. SLIMMER is identical to SLIM1 over the first three LIM domains but contains a novel C-terminal 96 amino acids with three potential bipartite nuclear localization signals, a putative nuclear export sequence, and 27 amino acids identical to the RBP-J binding region of KyoT2, a murine isoform of SLIM1. SLIM1 localized to the cytosol of Sol8 myoblasts and myotubes. SLIMMER was detected in the nucleus of myoblasts and, following differentiation into myotubes, was exclusively cytosolic. Recombinant green fluorescent protein-SLIM1 localized to the cytoplasm and associated with focal adhesions and actin filaments in COS-7 cells, while green fluorescent protein-SLIMMER was predominantly nuclear. SLIMMER truncation mutants revealed that the first nuclear localization signal mediates nuclear localization. The addition of the proposed nuclear export sequence decreased the level of exclusively nuclear expression and increased cytosolic SLIMMER expression in COS-7 cells. The leucine-rich nuclear export signal was required for the export of SLIMMER from the nucleus of myoblasts to the cytoplasm of myotubes. Collectively, these results suggest distinct roles for SLIM1 and SLIMMER in focal adhesions and nuclear-cytoplasmic communication.

Randomised, double-blind, placebo controlled pilot study assessing nitroglycerin as a tocolytic.

Thirty-three women in preterm labour were randomised in a double-blind fashion to receive either transdermal nitroglycerin (n = 17) or placebo (n = 16). Both groups had significant (P < 0.001) change in the cervix prior to randomisation. The primary outcome measure was delivery within 48 hours of randomisation. Fewer women randomised to nitroglycerin treatment (6/17) were delivered within 48 hours, compared with the placebo treatment (10/16) (RR 0.56, 95% CI 0.27 to 1.19). This pilot study lends support to two case series published that suggest that transdermal nitroglycerin may be promising as a safe, effective means for tocolysis.

Physical conditioning effects on fetal heart rate responses to graded maternal exercise.

PURPOSE: This study examined the effects of advancing gestational age and maternal aerobic conditioning (stationary cycling) on fetal heart rate (FHR) responses to strenuous non-steady-state maternal exercise. METHODS: Subjects chose to participate in either an exercise group (EG) or control group (CG). Fourteen healthy, previously sedentary pregnant women participated in the exercise group, and six pregnant controls remained sedentary. Stationary cycling (heart rate target: 145 beats x min(-1)) was performed 3 d x wk(-1) by the exercised group. Exercise duration was increased from 14 to 25 min x session(-1) during the second trimester and was maintained at 25 min x session(-1) throughout the third trimester. FHR was monitored before, during, and after a progressive submaximal cycle ergometer test (peak heart rate = 170 beats x min(-1)) performed at approximately 27 and 37 wk gestation. RESULTS: Mean FHR increased significantly (P < 0.05) during exercise, followed by a modest suppression and then a delayed rise during the recovery period at both observation times. Fetal bradycardia was not observed in any of the exercise tests. Effects of advancing gestational age included a lower FHR baseline both at rest and in response to maternal exercise and a lower incidence of exercise-induced tachycardia. Maternal physical conditioning did not significantly alter FHR response to maternal exercise. CONCLUSION: Our results support the hypothesis that FHR responses to strenuous exercise are altered by advancing gestational age and a brief progressive exercise test terminated at a maternal heart rate of 170 beats x min(-1) does not induce fetal distress during a healthy pregnancy.

Behavioral effects of cocaine on a transgenic mouse model of cortical-limbic compulsion.

We previously created a transgenic mouse model of cortical-limbic induced compulsions in which dopamine D1 receptor-expressing (D1+) neurons in restricted regional subsets of the cortex and amygdala express a neuropotentiating cholera toxin (CT) transgene. These 'D1CT' mice engage in complex behavioral abnormalities uniquely resembling human compulsions, such as non-aggressive biting of cagemates during grooming, repeated leaping and episodes of perseverance of any and all normal behaviors. Because both compulsions and cocaine-induced behaviors may represent forms of psychomotor activation that have a shared or overlapping neurological basis, we have examined the behavioral response of these 'compulsive' mice to cocaine. In both control and D1CT mice, cocaine increased the amount of time spent engaged in typical cocaine-dependent stereotypies such as locomotion, sniffing, or gnawing, while the remainder of behaviors within their normally complete behavioral repertoires decreased. Cocaine also decreased, rather than facilitated, the incidence of D1CT transgene-induced compulsion-like behaviors such as repeated leaping and perseverance of any and all normal behaviors. The indistinguishable cocaine responses of D1CT and normal mice, as well as the masking (rather than potentiation) of D1CT mouse compulsion-like behaviors by cocaine, suggests that cortical-limbic induced compulsions are significantly different in their origin or circuitry from cocaine-induced stereotyped behaviors. Specifically, these data suggest that the motor circuits stimulated in compulsions represent only a subset of the parallel circuits stimulated by cocaine. These data are, thus, consistent with the hypothesis that topographically restricted subsets of parallel cortical-striatal-thalamic loops induce different types of compulsive behaviors.

OCD-Like behaviors caused by a neuropotentiating transgene targeted to cortical and limbic D1+ neurons.

To study the behavioral role of neurons containing the D1 dopamine receptor (D1+), we have used a genetic neurostimulatory approach. We generated transgenic mice that express an intracellular form of cholera toxin (CT), a neuropotentiating enzyme that chronically activates stimulatory G-protein (Gs) signal transduction and cAMP synthesis, under the control of the D1 promoter. Because the D1 promoter, like other CNS-expressed promoters, confers transgene expression that is regionally restricted to different D1+ CNS subsets in different transgenic lines, we observed distinct but related psychomotor disorders in different D1CT-expressing founders. In a D1CT line in which transgene expression was restricted to the following D1+ CNS regions-the piriform cortex layer II, layers II-III of somatosensory cortical areas, and the intercalated nucleus of the amygdala-D1CT mice showed normal CNS and D1+ neural architecture but increased cAMP content in whole extracts of the piriform and somatosensory cortex. These mice also exhibited a constellation of compulsive behavioral abnormalities that strongly resembled human cortical-limbic-induced compulsive disorders such as obsessive-compulsive disorder (OCD). These compulsive behaviors included episodes of perseverance or repetition of any and all normal behaviors, repetitive nonaggressive biting of siblings during grooming, and repetitive leaping. These results suggest that chronic potentiation of cortical and limbic D1+ neurons thought to induce glutamatergic output to the striatum causes behaviors reminiscent of those in human cortical-limbic-induced compulsive disorders.

Differential response of cortical-limbic neuropotentiated compulsive mice to dopamine D1 and D2 receptor antagonists.

We previously created transgenic mice in which dopamine D1 receptor-expressing (D1+) neurons in regional subsets of the cortex and amygdala express a neuropotentiating cholera toxin (CT) transgene. These 'D1CT' mice engage in complex biting, locomotor and behavioral perseverance-repetition abnormalities that resemble symptoms of human compulsive disorders associated with cortical-limbic hyperactivity. Because excessive cortical-limbic stimulation of striatal motor pathways may play a critical role in causing compulsive disorders, we examined the responsiveness of D1CT mice to dopamine D1 and D2 receptor antagonists. D1CT mice were found to be largely resistant to the cataleptic action of the D1 receptor antagonist SCH23390. The abnormal repetitive leaping of D1CT mice was similarly unaffected by SCH23390. In contrast, the D1CT mice displayed supersensitivity to cataleptic induction by the D2 receptor antagonist sulpiride. These data are consistent with the hypothesis that complex compulsions are mediated by chronic excessive corticostriatal (and/or amygdalostriatal) glutamatergic stimulation of the striatal direct and indirect motor pathways.

The cardiac expression of striated muscle LIM protein 1 (SLIM1) is restricted to the outflow tract of the developing heart.

LIM proteins perform critical roles in development and tissue differentiation. The skeletal muscle LIM protein 1 (SLIM1) comprises four and a half LIM domains. Northern blot analysis demonstrated high level expression of SLIM1 mRNA in adult human skeletal muscle with intermediate expression in adult heart and lower expression in other tissues. Western blot analysis using specific affinity-purified anti-SLIM1 antipeptide antibodies demonstrated a 32 kDa polypeptide in the aorta and atria of rabbit heart, but not in vena cava, interventricular septum or ventricular muscle. SLIM1 was also demonstrated in rabbit skeletal muscle. In situ hybridization of whole mouse embryos confirmed the cardiac expression of SLIM1 was restricted to the cardiac outflow tract from embryonic day 8.5-11. No expression was seen in atrial or ventricular muscle. SLIM1 mRNA was also demonstrated in the hindbrain, neural tube and somites. The localized expression of SLIM1 to the outflow tract of the embryonic heart implies an important role for the protein in the development of this region and possibly in congenital heart anomalies involving the separation and formation of the aortic and pulmonary trunks.

The role of cognitive and affective processing in a transgenic mouse model of cortical-limbic neuropotentiated compulsive behavior.

Obsessive compulsive disorder (OCD) may involve abnormal cortical-limbic processing or responsiveness. Mice with behaviors resembling the symptoms of OCD and related disorders were made by expression of a neuropotentiating cholera toxin (CT) transgene in cortical-limbic D1 receptor-expressing neurons. Because these D1CT mice express CT in the piriform cortex and amygdala (major cognitive and affective olfactory processing areas) it was tested whether abnormal odor perception, discrimination, or responsiveness facilitates their compulsion-like behavior. The mice exhibited normal olfactory discriminative capability. An anxiogenic odor potentiated their abnormal repetitive leaping, but novel or familiar nonthreatening odors did not. These data suggest that compulsions can be triggered not by impaired cortical-limbic processing but by increased cortical-limbic responsiveness, particularly to sensory or cognitive stimuli with affective properties.

Anxiety in a transgenic mouse model of cortical-limbic neuro-potentiated compulsive behavior.

Anxiety and amygdalar stimulation may induce or exacerbate compulsions triggered by cortical-limbic hyperactivity, as in human obsessive-compulsive disorder (OCD). We previously created transgenic mice that exhibit OCD-like biting, movement and behavioral perseverance abnormalities. These behaviors are caused by expression of a neuro-potentiating cholera toxin (CT) transgene in dopamine D1 receptor-expressing (D1+) neurons within the amygdalar intercalated nucleus (ICN) and within cortical areas that project to orbitofrontal cortex and striatum. Here we tested whether anxiety and increased amygdalar stimulation may play a role in eliciting or exacerbating such behaviors. D1CT mice exhibited increased thigmotaxis (tendency of mice to remain along the perimeter of open areas) in the open field assay, and increased latency to first transit and reduced transit number in the light-dark assay. These studies indicate that the D1CT mice exhibit a significant increase in behavioral indicators of anxiety. Furthermore, yohimbine, a drug that induces both amygdalar stimulation and behavioral indicators of anxiety, exacerbated abnormal leaping in D1CT mice but failed to exacerbate their abnormal behavioral perseverance. These data suggest that chronic potentiation of D1+ neurons in the amygdalar ICN increases anxiety and facilitates particular compulsive behaviors.