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Dual task performance after diazepam intake: can resource depletion explain the benzodiazepine-induced amnesia?

It was tested whether a depletion in resources can account for the benzodiazepine-induced memory impairment. In two experiments, it was examined whether dividing attention had a disproportionately detrimental effect on learning semantically related and unrelated word pairs after diazepam intake. Word pairs had to be learned in both a single task condition and while performing a visual discrimination task concurrently (dual task condition). Moreover, the complexity of the visual discrimination task was manipulated systematically. Diazepam (15 mg, orally) or placebo was administered in a double-blind, between-subjects design. Subjects after diazepam intake were clearly impaired in learning unrelated word pairs, but not in learning related word pairs. Dividing attention in the dual task condition was associated with a reduction in learning unrelated word pairs, but this was not disproportionately reduced after diazepam intake. Moreover, the magnitude of resource depletion did not correlate with the severity of the diazepam-induced memory impairment. In general, the pattern of results does not support the hypothesis that a depletion of resources can explain the benzodiazepine-induced memory impairment.

Adult↗

Modeling facilitative sugar transporters: transitions between single and double ligand occupancy of multiconformational channel models explain anomalous kinetics.

The four-state simple carrier model (SCM) is employed to describe ligand translocation by diverse passive membrane transporters. However, its application to systems like facilitative sugar transporters (GLUTs) is controversial: unidirectional fluxes under zero-trans and equilibrium-exchange experimental conditions fit a SCM, but flux data from infinite-cis and infinite-trans experiments appear not to fit the same SCM. More complex kinetic models have been proposed to explain this "anomalous" behavior of GLUTs, but none of them accounts for all the experimental findings. We propose an alternative model in which GLUTs are channels subject to conformational transitions, and further assume that the results from zero-trans and equilibrium-exchange experiments as well as trans-effects corresponds to a single-occupancy channel regime, whereas the results from the infinite-cis and infinite-trans experiments correspond to a regime including higher channel occupancies. We test the plausibility of this hypothesis by studying a kinetic model of a two-site channel with two conformational states. In each state, the channel can bind the ligand from only one of the compartments. Under single-occupancy, for conditions corresponding to zero-trans and equilibrium-exchange experiments, the model behaves as a SCM capable of exhibiting trans-stimulations. For a regime including higher degrees of occupancy and infinite-cis and infinite-trans conditions, the same channel model can exhibit a behavior qualitatively similar to a SCM, albeit with kinetic parameters different from those for the single-occupancy regime. Numerical results obtained with our model are consistent with available experimental data on facilitative glucose transport across erythrocyte membranes. Hence, if GLUTs are multiconformational channels, their particular kinetic properties can result from transitions between single and double channel occupancies.

Carbohydrate Metabolism↗

Heterozygote advantage fails to explain the high degree of polymorphism of the MHC.

Major histocompatibility (MHC) molecules are encoded by extremely polymorphic genes and play a crucial role in vertebrate immunity. Natural selection favors MHC heterozygous hosts because individuals heterozygous at the MHC can present a larger diversity of peptides from infectious pathogens than homozygous individuals. Whether or not heterozygote advantage is sufficient to account for a high degree of polymorphism is controversial, however. Using mathematical models we studied the degree of MHC polymorphism arising when heterozygote advantage is the only selection pressure. We argue that existing models are misleading in that the fitness of heterozygotes is not related to the MHC alleles they harbor. To correct for this, we have developed novel models in which the genotypic fitness of a host directly reflects the fitness contributions of its MHC alleles. The mathematical analysis suggests that a high degree of polymorphism can only be accounted for if the different MHC alleles confer unrealistically similar fitnesses. This conclusion was confirmed by stochastic simulations, including mutation, genetic drift, and a finite population size. Heterozygote advantage on its own is insufficient to explain the high population diversity of the MHC.

Animals↗

Topoisomerase II alpha content and topoisomerase II catalytic activity cannot explain drug sensitivities to topoisomerase II inhibitors in lung cancer cell lines.

PURPOSE: Topoisomerase II alpha content, topoisomerase II catalytic activity and drug sensitivities to the topoisomerase II inhibitors, doxorubicin and etoposide, were examined in a panel of 14 unselected human lung cancer cell lines in order to determine the relationship between topoisomerase II and drug sensitivities to the topoisomerase II inhibitors. METHODS: Drug sensitivities were determined using a microculture tetrazolium assay. The topoisomerase II alpha levels were determined by Western blot analysis and the topoisomerase II catalytic activity was determined using a decatenation assay of kinetoplast DNA, using nuclear protein from cells of each cell line. RESULTS: Drug sensitivity tests revealed that small-cell lung cancer (SCLC) cell lines were more sensitive to drugs than non-small-cell lung cancer (NSCLC) cell lines. The relative topoisomerase II alpha levels and relative topoisomerase II catalytic activity from SCLC cell lines (mean +/- SD 0.89 +/- 0.54 and 5.3 +/- 3.4, respectively) were slightly higher than those from NSCLC cell lines (0.78 +/- 0.56 and 4.0 +/- 2.8, respectively), but the differences were not statistically significant, and not sufficient to account for the variation in drug sensitivities. Moreover, no clear association was observed between the topoisomerase II alpha levels or the topoisomerase II catalytic activity and drug sensitivities in the cell lines studied. CONCLUSIONS: These findings suggest that the difference in drug sensitivities to doxorubicin and etoposide in human lung cancer cell lines might not be explainable by the topoisomerase II alpha levels and topoisomerase II catalytic activity. Moreover, our results suggest that the topoisomerase II alpha levels and topoisomerase II catalytic activity may play a minor role in the determination of clinical drug resistance of human lung cancers.

Adenocarcinoma↗

The patient's informed consent for pacemakers and ICD implantation: how to write and how to explain it.

Written informed consent for pacemaker and ICD patients should be easy to understand and provided in written form in the patient's language. Comprehensiveness is required. It is essential to address driving and running machines, complication rates, benefits in appropriate hierarchical order and future necessary interventions. Eventually potential risks, e.g., flying, sports, sexual activity should be mentioned. It is important to explain pacemaker systems and ICD devices in details including cardiac resynchronization therapy (CRT) for heart failure. One of the main aspects concerns protection of human subjects participating in clinical studies. Informed consent necessitates a statement that the study involves research. This statement should include explanation of the purposes of the study, expected duration, description of the procedures, identification of experimental procedures, description of foreseeable risks or discomforts, and disclosure of alternative procedures. Further information should be given on psychological concerns, sexual activity, driving and quality of life in pacemaker and ICD patients.

Adult↗

Need and demand in psychiatric emergency service utilization: explaining topographic differences of a utilization sample in Mannheim.

Up to now all investigations about the topographic distribution of psychiatric utilization rates ignore whether or not the patients really require care (need for care) respectively express that need by themselves (demand for care). To analyze utilization rates of the psychiatric emergency service of the Central Institute of Mental Health in Mannheim (CIMH), variables differentiating between need and demand for emergency care were included. The investigation is based on contacts in the psychiatric emergency service between 1982 and 1993 and comprises 6463 patients with 14,628 contacts. To operationalize the concepts of need and demand the items "instance of consultation", "reasons for consultation", "inpatient admission" and "rated urgency" from the standardized record system of the psychiatric emergency service were used. The association between need, demand and ecological, socio-demographic and distance-related factors were analyzed. The results show that demand for psychiatric emergency care is an important factor for explaining topographic differences in service utilization. Demand correlates with ecological, socio-demographic and distance related factors; need only correlates with age. The amount of demand also varies with specific mental disorders.

Emergency Services, Psychiatric↗

Maximal strength-training effects on force-velocity and force-power relationships explain increases in aerobic performance in humans.

Maximal strength-training with an emphasis on maximal mobilization during cross-country skiing increases exercise economy when double-poling. The aim of this experiment was to investigate whether the mechanism of this increase is a change in the force-velocity relationship and the mechanical power output. A group of 19 cross-country skiers having an average peak oxygen uptake of 255 ml x kg(-0.67) body mass x min(-1) or 61 ml x kg(-1) x min(-1) were randomly assigned to either a high resistance-training group (n=10) or a control group (n=9). Upper body endurance was tested on a ski ergometer. The high-resistance-training group trained for 15 min on three occasions a week for 9 weeks. Training consisted of three series of five repetitions using 85% of one repetition maximum (1RM), with emphasis on high velocity in the concentric part of the movement. Upper body exercise economy, 1RM and time to exhaustion increased significantly in the high resistance-training group, but was unchanged in the control group. Peak power and the velocities for a given load increased significantly, except for the two lowest loads. We conclude that the increased exercise economy after a period of upper body high resistance-training can be partly explained by a specific change in the force-velocity relationship and the mechanical power output.

Adult↗

The generalized force-velocity relationship explains why the preferred pedaling rate of cyclists exceeds the most efficient one.

The most efficient pedaling rate (lowest oxygen consumption) at a workload of 50-300 W has been reported to be in the range of 42-60 rpm. By contrast, most competitive cyclists prefer a pedaling rate of more than 90 rpm. The reason for this difference is still unknown. We assume that the high pedaling rate preferred by cyclists can be explained by the inherent properties of muscle fibers. To obtain statements which do not depend on muscle's cross-section and length, we generalized Hill's characteristic equations where muscle force and heat liberation are related to shortening velocity. A pedaling rate of f (etamax) yields to maximal efficiency, whereas the higher pedaling rate f (Pmax) leads to maximal power. The ratio f (Pmax)/f (etamax) between these two pedaling rates ranges from 1.7 to 2.4, and it depends on the muscle's fiber-type composition. In sprints and competitions of very short duration, f (Pmax) is more advantageous because energy supply is not the predominant limiting factor. The price to be paid for the most powerful pedaling rate is lower efficiency and higher energy cost. In longer exercises, economy is more important and the optimal pedaling rate shifts toward f (etamax). We conclude that the optimal pedaling rate, representing the fastest race performance, is not fixed but depends on race duration; it ranges between f (etamax) and f (Pmax). Our results are not only of interest for competitive cyclists but also for investigations using cycle ergometers: maximum power might not be reached by using a pedaling rate near the most efficient one.

Computer Simulation↗

The postural reduction in middle cerebral artery blood velocity is not explained by PaCO2.

In the normocapnic range, middle cerebral artery mean velocity (MCA Vmean) changes approximately 3.5% per mmHg carbon-dioxide tension in arterial blood (PaCO2) and a decrease in PaCO2 will reduce the cerebral blood flow by vasoconstriction (the CO2 reactivity of the brain). When standing up MCA Vmean and the end-tidal carbon-dioxide tension (PETCO2) decrease, suggesting that PaCO2 contributes to the reduction in MCA Vmean. In a fixed body position, PETCO2 tracks changes in the PaCO2 but when assuming the upright position, cardiac output (Q) decreases and its distribution over the lung changes, while ventilation (VE) increases suggesting that PETCO2 decreases more than PaCO2. This study evaluated whether the postural reduction in PaCO2 accounts for the postural decline in MCA Vmean). From the supine to the upright position, VE, Q, PETCO2, PaCO2, MCA Vmean, and the near-infrared spectrophotometry determined cerebral tissue oxygenation (CO2Hb) were followed in seven subjects. When standing up, MCA Vmean (from 65.3+/-3.8 to 54.6+/-3.3 cm s(-1) ; mean +/- SEM; P<0.05) and cO2Hb (-7.2+/-2.2 micromol l(-1) ; P<0.05) decreased. At the same time, the VE/Q ratio increased 49+/-14% (P<0.05) with the postural reduction in PETCO2 overestimating the decline in PaCO2 (-4.8+/-0.9 mmHg vs. -3.0+/-1.1 mmHg; P<0.05). When assuming the upright position, the postural decrease in MCA Vmean seems to be explained by the reduction in PETCO2 but the small decrease in PaCO2 makes it unlikely that the postural decrease in MCA Vmean can be accounted for by the cerebral CO2 reactivity alone.

Adult↗

A comparison of models explaining muscle activation patterns for isometric contractions.

One of the main problems in motor-control research is the muscle load sharing problem, which originates from the fact that the number of muscles spanning a joint exceeds the number of degrees of freedom of the joint. As a consequence, many different possibilities exist for the activation of muscles in order to produce a desired joint torque. Several models describing muscle activation have been hypothesized over the last few decades to solve this problem. This study presents theoretical analyses of the various models and compares the predictions of these models with new data on muscle activation patterns for isometric contractions in various directions. None of the existing models fitted the experimental data in all aspects. The best fit was obtained by models based on minimization of the squared sum of muscle forces ( summation operator(m)&phi;(2)(m), which is almost equivalent to the Moore-Penrose pseudo-inverse solution), muscle stress sigma ( summation operator(m)sigma(m)(2)) or muscle activation alpha ( summation operator(m)alpha(m)(2)). Since muscle activation patterns are different for isometric contractions and for movements, it could well be that other models or optimization criteria are better suited to describe muscle activation patterns for movements. The results of our simulations demonstrate that the predicted muscle activation patterns do not depend critically on the parameters in the model. This may explain why muscle activation patterns are highly stereotyped for all subjects irrespective of differences between subjects in many neuro-anatomical aspects, such as, for example, in the physiological cross-sectional area of muscle.

Models, Biological↗

Parasite mediated mortality and host immune response explain age-related differences in blood parasitism in birds.

An important pattern in host-parasite assemblages is a higher intensity of parasites in juveniles than in adults, but the reasons for these differences remain obscure. Three non-mutually exclusive hypotheses have been proposed: (1) heavily parasitized juveniles die before being recruited into the adult population ('selection' hypothesis); (2) the development of an acquired immunity by the host in front of the parasite reduces the intensity of the parasite in adult hosts ('immunity' hypothesis); and (3) differences in behavior makes adults less exposed to the parasite than juveniles ('vector exposure' hypothesis). Having rejected the 'vector exposure' hypothesis in a previous study, here we tested the 'selection' and 'immunity' hypotheses in feral pigeons (Columba livia) infected by the blood parasite Haemoproteus columbae. In agreement with the 'selection' hypothesis, young (but not adult) pigeons that were highly parasitized had a lower probability of surviving until adulthood, independent of their body condition. However, selection was not strong enough to account for the observed differences in parasite intensity between age-classes, and after selection parasite intensity of survivors still remained 85% higher in juveniles than in adults. In contrast, the 'immunity' hypothesis offered a greater explanatory power. The intensity of blood parasites in young pigeons, but not in adults, decreased over time so dramatically that by the time they had become adults their intensities were indistinguishable from that typically seen in adults. Therefore, while selection against highly parasitized juveniles can contribute to some extent to a reduction in parasitism seen in the adult population, age-specific blood parasitism in feral pigeons is best explained as a transitory phase just before the host develops an effective immune response.

Age Factors↗

Does initial litter chemistry explain litter mixture effects on decomposition?

We tested the hypothesis that interactions in litter mixtures (expressed as the difference between observed and expected decomposition rates) are greater when the component species differ more in their initial litter chemistry. Thereto, we collected freshly senesced leaf litter from a wide range of species from an old field and woodland vegetation, and a fen ecosystem in The Netherlands. Litterbags with either mono-specific litter (20 and 15 species), or litter mixtures (50 and 42 species pairs) of randomly drawn combinations of two representatives from different plant functional types were incubated for 20, 35 and 54 weeks in a purpose-built decomposition bed (woodland/old field) or in the field (fen). Species showed a wide range of decomposition rates. For the woodland/old field species, initial litter C and P concentrations were significantly correlated with litter decomposition rate. For the fen species, litter phenolics concentration was correlated with decomposition rate. If the Sphagnum species were left out of the analyses, initial litter P and phenolics concentration both showed a significant relationship, albeit only with the remaining mass after 1 year. Differences between observed and expected decomposition were often considerable in individual litter mixtures. Regression analysis showed that such differences were not related to the differences in litter chemistry of the component species. Furthermore, litter mixtures containing species with very different initial litter chemistry did not show stronger interaction when tested against litter mixtures containing chemically similar litter types. From these observations we conclude that the difference in initial single litter chemistry parameters of the component is not a useful concept to explain interactions in litter mixtures.

Biodegradation, Environmental↗

Foliar pH as a new plant trait: can it explain variation in foliar chemistry and carbon cycling processes among subarctic plant species and types?

Plant traits have become popular as predictors of interspecific variation in important ecosystem properties and processes. Here we introduce foliar pH as a possible new plant trait, and tested whether (1) green leaf pH or leaf litter pH correlates with biochemical and structural foliar traits that are linked to biogeochemical cycling; (2) there is consistent variation in green leaf pH or leaf litter pH among plant types as defined by nutrient uptake mode and higher taxonomy; (3) green leaf pH can predict a significant proportion of variation in leaf digestibility among plant species and types; (4) leaf litter pH can predict a significant proportion of variation in leaf litter decomposability among plant species and types. We found some evidence in support of all four hypotheses for a wide range of species in a subarctic flora, although cryptogams (fern allies and a moss) tended to weaken the patterns by showing relatively poor leaf digestibility or litter decomposability at a given pH. Among seed plant species, green leaf pH itself explained only up to a third of the interspecific variation in leaf digestibility and leaf litter up to a quarter of the interspecific variation in leaf litter decomposability. However, foliar pH substantially improved the power of foliar lignin and/or cellulose concentrations as predictors of these processes when added to regression models as a second variable. When species were aggregated into plant types as defined by higher taxonomy and nutrient uptake mode, green-specific leaf area was a more powerful predictor of digestibility or decomposability than any of the biochemical traits including pH. The usefulness of foliar pH as a new predictive trait, whether or not in combination with other traits, remains to be tested across more plant species, types and biomes, and also in relation to other plant or ecosystem traits and processes.

Animals↗

Multi-Unit and Multi-Path system of the neural network can explain the steep dose-response of MAC.

PURPOSE: The slope of the dose-response curves of inhalation anesthetics is steep around the minimum alveolar concentration of inhalation anesthetics (MAC) value. Contrastingly, the anesthetic dose-response curves of ion channels and enzymes are gradual. This discrepancy in the steepness may be a key to solve the mechanisms of anesthesia. To explain the steepness we propose a mathematical model of the neural network related to MAC. METHODS: We assumed that, in order to show movement in response to a noxious stimulus, a signal needed to be transmitted from A to B. There are m conduction pathways (Multi-Path) in the nerve network between A and B, and there are n conduction units (Multi-Unit) in each conduction pathway. Anesthetics bind to each conduction unit and block signal transmission. Anesthetics prevent movement in response to a stimulus, when at least one conduction unit among all conduction pathways has been blocked. We derived the equation for the probability of the signal being blocked by anesthetics. RESULTS: The steep dose-response curve of in vivo anesthesia requires a very large number of conduction units ( n > 100) and conduction pathways ( m > 10(6)). The EC50 for each conduction unit was at least 3.8-fold larger than the apparent EC50 for the whole system under the experimental condition of simulation. CONCLUSIONS: We constructed a model for the neural networks that relates to MAC as a Multi-Unit and Multi-Path system (MUMPS). To obtain highly cooperative dose-response curves comparable to those of in vivo anesthesia, at least 10(6) conduction pathways and more than 100 conduction units are required for each pathway. In these systems, the apparent anesthetic potency on the whole system (MAC) is much stronger than the anesthetic action on each unit. Because of this discrepancy, it is important to set anesthetic concentrations appropriately for experiments with in vitro systems.

Anesthetics, Inhalation↗

Neurovascular compression syndrome of the eighth cranial nerve. Can the site of compression explain the symptoms?

Considerable skepticism still exists concerning the concept of neurovascular compression (NVC) syndromes of the eighth cranial nerve (8th N). If such syndromes exist, the sites of compression of the nerve must explain the symptoms encountered. We recorded compound action potentials of the cochlear nerve (CCAPs) during neurovascular decompression (NVD) to examine the topography of the three components of the 8th N. The sites of compression of the 8th N in cases of NVC syndrome confirmed at surgery were superimposed on the topography of the CN and vestibular nerve (VN) in order to determine the relationship between the sites of compression and the symptoms. CCAPs were clearly and consistently recorded on the caudal surface of the 8th N along the midline. In patients with vertigo and tinnitus there was vascular compression of the rostroventral (VN) and caudal surface (CN) of the nerve, respectively. In patients with both vertigo and tinnitus, there was compression of both VN and CN. Our findings clearly demonstrate that the symptoms of NVC of the 8th N depend on the part of the nerve that is compressed by blood vessels, and they support the concept of NVC syndrome of the 8th N.

Action Potentials↗

Can gender differences in the prevalence of mental disorders be explained by sociodemographic factors?

BACKGROUND AND AIMS: Epidemiological studies throughout the world consistently reported higher rates of depression and anxiety disorders in women, whereas men consistently show higher rates of substance and antisocial disorders. The present study examined factors potentially contributing to these gender differences using general population data. METHODS: The sample was drawn from population registries (N=4181) and can be regarded as representative for the adult German population aged 18-65. Mental disorders (DSM-IV) were assessed with a diagnostic interview (CIDI) carried out by clinically trained interviewers. A range of sociodemographic variables was analysed within men, within women, and between genders. RESULTS: The prevalence of common mental disorders (mood, anxiety, substance use and somatoform disorders) is higher among females, with the exception of substance use disorders. Young age was related to substance disorders both in women and in men. Not being married and being unemployed were associated with increased rates of mental disorders in both sexes, but in men stronger than in women. Being retired was associated with depression only in women, whereas belonging to a higher social class, working fulltime and having children appeared to be protective factors for men only. Other sociodemographic factors (concerning education, employment and family status) were not associated with increased rates of mental disorders both in women and men. CONCLUSION: Overall the emotional advantages or disadvantages of marital status, employment status, number of children, parenthood and social class apply equally to men and women. We cannot explain the female preponderance in most mental disorders by detecting specific unfavourable patterns of sociodemographic correlates, suggesting that determinants of gender differences in common mental disorders are still far from being understood.

Adolescent↗

Normal female anal sphincter: difficulties in interpretation explained.

PURPOSE: Our aims were to quantify the nature, characteristics, and frequency of variations in female anal sphincter anatomy. METHODS: Nulliparous patients from the antenatal clinic and healthy volunteers of both genders were studied. Sphincter length was determined by the position of the puborectalis sling. Defects in the external anal sphincter were defined at each level and recorded in degrees. Cylindric longitudinal images of the endoanal scans were created by a three-dimensional-representation software package. Manometry was performed by a pull-through technique. RESULTS: Fifty-seven nulliparous patients and 18 healthy volunteers were included in the study. The mean age was 39 years for males and 28.35 years for females. There was no significant difference in overall sphincter length or in the internal anal sphincter length as a percentage of overall sphincter length between genders. All nine males had a complete ring of external anal sphincter along the full sphincter length. In the external anal sphincter below the level of the puborectalis sling, a natural gap occurred in 43 nulliparous (75 percent) and all 9 female volunteers. The greater the size of the defect, the greater its extent (mean 1.33 cm for >90 degrees and 1.16 cm for <90 degrees; chi-squared P = 0.008, eight degrees of freedom). Manometry provided confirmatory evidence of the gaps seen. Anal manometry was analyzed by Mann-Whitney U test for continuous nonparametric data and t-test for comparison between genders. CONCLUSION: The female sphincter has a variable natural defect occurring along its anterior length. This makes interpretation of the isolated endoanal ultrasound difficult and explains previous overreporting of obstetric sphincter defects.

Adult↗

Explaining change over time in quality of life of adult patients with anorectal malformations or Hirschsprung's disease.

PURPOSE: The aim of this study was to examine changes in the quality of life of adult patients with anorectal malformations or Hirschsprung's disease over a three-year interval and to identify demographic, clinical, and psychosocial variables that explain possible quality-of-life changes. Understanding the factors that affect changes in quality of life over time is particularly important to provide adequate care. METHODS: Questionnaires were administered to 261 patients (77 percent), with a three-year interval. Background characteristics, including demographic and clinical variables, and psychosocial variables (i.e., self-esteem, mastery, social support, disease cognition) were measured on one occasion. Generic and disease-specific quality of life were measured twice. RESULTS: On average patients indicated no change in quality-of-life level after three years. However, variance in the change scores revealed individual variation, indicating the presence of patients who improved and patients who deteriorated. Patients who were female, older, have other congenital diseases, or a stoma reported poorer quality of life over time. The psychosocial variable "disease cognition" most strongly affected the change in quality of life of patients with anorectal malformations or Hirschsprung's disease. CONCLUSIONS: Our results could alert clinicians to patients who are at risk for quality-of-life deterioration and might therefore be in need for extra care. Our findings illustrate the importance of psychosocial functioning for enhancing the quality of life over time of these patients.

Adolescent↗