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Polysomnographic analysis of arousal responses in obstructive sleep apnea syndrome by means of the cyclic alternating pattern.

Obstructive sleep apnea syndrome (OSAS) is characterized by multiple interruptions of airflow between periods of arousals. A key feature of OSAS is the 20- to 40-s cyclic pattern of electrophysiologic parameters. The periodicity of the OSAS-related phenomena is reminiscent of the natural electroencephalographic (EEG) arousal rhythm of non-rapid eye movement (NREM) sleep known as the cyclic alternating pattern (CAP). Morphologically, CAP consists of transient arousals (phase A) that periodically interrupt the tonic theta/delta activities of NREM sleep (phase B). Functionally, CAP translates a condition of sustained arousal instability oscillating between a greater arousal level (phase A) and a lesser arousal level (phase B). CAP is also related to the controls of the motor and autonomic mechanisms. On the basis of the information simultaneously derived from EEG activities, muscle tone, and neurovegetative responses, it is possible to distinguish three subtypes of A phases corresponding to different levels of arousal power: A1 (dominated by EEG synchronization and weak activation of polygraphic variables); A2 (mixture of EEG synchronization/desynchronization and intermediate activation of polygraphic variables); and A3 (dominated by EEG desynchronization and strong activation of polygraphic variables). Unlike standard criteria, CAP parameters offer a more suitable perspective for evaluating sleep pathologies in which brief and frequent arousals appear as a prominent feature. The present study aimed at (a) assessing CAP parameters in OSAS patients and (b) investigating the reciprocal interactions between CAP and the cyclic variations in respiratory rate. Twelve obese middle-aged OSAS subjects complaining of daytime sleepiness were polygraphically compared with age-matched and gender-matched volunteers in good health and with no complaints about sleep and wakefulness (controls). In OSAS patients, conventional parameters showed predictable decrements in total sleep time, slow wave sleep, and REM sleep and increases in stage 1 and nocturnal awakenings. Sleep fragmentation was associated with a significant enhancement of CAP and of the A phases with longer and more desynchronized EEG patterns (especially A3). The increase of A3 subtypes permitted scoring and detecting CAP also in REM sleep. The great majority of respiratory pauses (96% in NREM and 80% in REM sleep) were coupled with CAP. All CAP-related respiratory events rose in close temporal connection with a phase B, while effective breathing was always recovered during phase A (especially A2 and A3 subtypes). These data suggest that (a) phase B of CAP offers a vulnerable background for upper airway collapse and for attenuation of biochemical and neural mechanisms in the control of the ventilatory drive and (b) survival in OSAS patients is effected by the enhancement of the strongest components of the natural arousal rhythm at sleep quality's expense.

Arousal↗

Hepatic stellate cells express synemin, a protein bridging intermediate filaments to focal adhesions.

BACKGROUND AND AIMS: In the liver, stellate cells play several important (patho)physiological roles. They express a broad but variable spectrum of intermediate filament (IF) proteins. The aim of this study was to investigate the expression and functions of the intermediate filament protein synemin in hepatic stellate cells (HSCs). METHODS: In isolated and cultured rat HSCs, synemin expression was examined by quantitative reverse transcriptase polymerase chain reaction, western blotting, and immunocytochemistry. Protein-protein interaction between synemin and possible binding partners was investigated by co-immunoprecipitation and confocal microscopy. RESULTS: Expression of synemin was significantly downregulated with increased culture time. In 1-day cultured HSCs, synemin associated with other IF proteins (GFAP, desmin, and vimentin), and with the focal adhesion proteins vinculin and talin, but not with alpha-actinin or paxillin. Synemin IF and focal adhesion proteins co-localised in long slender processes, but not in the lamellipodia. In human and rat liver tissue, the presence of synemin was investigated by immunohistochemistry. In normal rat and human livers, synemin immunoreactivity was found in HSCs, smooth muscle cells of hepatic arterioles, and nerve bundles in portal tracts, but not in portal fibroblasts. In CCl4-intoxicated rat livers and in human cirrhotic livers, immunoreactivity for synemin in the parenchymal tissue was decreased. Thus synemin was expressed in quiescent HSCs but not in portal fibroblasts; and synemin expression decreased with HSC activation in vivo during chronic liver damage and with HSC activation in culture. CONCLUSIONS: Synemin forms heteropolymeric filaments with type-III IF proteins and acts as a bridging protein between IFs and a specific type of focal adhesions.

Animals↗

[Predictive model for cocaine use in prisons in Rio de Janeiro, Brazil].

OBJECTIVE: To identify predictors of and groups vulnerable to cocaine use in prison. METHODS: We selected 376 inmates with history of cocaine use in prison (cases) and 938 inmates with no history of drug use (controls) serving sentences in the Rio de Janeiro State prison system in 1998. The analysis included exposure variables divided into three hierarchical levels: distal, intermediate, and proximal. We performed bivariate analysis using logistic regression and multivariate analysis using hierarchized regression; results are given in odds ratios. RESULTS: Variables associated with cocaine use in prison in the proximal level were use of alcohol and marijuana and duration of imprisonment in years. The effect of social vulnerability variables (distal level) was intermediated by variables in the next levels. Considering only the distal and intermediate levels, use of marijuana prior to imprisonment (OR=4.50; 95% CI: 3.17-6.41) and offence in order to obtain drugs (OR=2.96; 95% CI: 1.79-4.90) showed the strongest association with the outcome. For every additional year spent in prison, the odds of cocaine use increase by 13% (OR=1.13; 95% CI: 1.06-1.21). CONCLUSIONS: Considering the distal and intermediate levels, use of marijuana prior to imprisonment and perpetration of offence in order to obtain drugs were the variables with greatest predictive value. The final model showed alcohol and marijuana use in prison and duration of imprisonment as important predictors of the outcome. The prison environment appears as a factor stimulating drug use.

Adult↗

Expression of integrin receptors on 45 clinical neuroblastoma specimens.

Immunohistological expression of integrins has been analyzed on 45 neuroblastoma specimens representative of the different clinical and histological forms of the tumor. None of the specimens expressed the alpha 5 chain of the integrins. The beta 1 chain was expressed on all specimens, the alpha 1 chain on 44 specimens and the alpha 3 chain on 42; the 4 specimens which lacked alpha 1 or alpha 3 were stage-4 neuroblastomas. The alpha 2 chain was expressed on 18 specimens, and the alpha 6 chain on 17; 15 reacted with both. Their reactivity was related to the maturation of the tumor rather than the stage of the disease: they were expressed on low-grade, well-differentiated specimens; stage 3-4 neuroblastoma specimens analyzed at diagnosis were negative, but usually expressed both chains when analyzed after in vivo differentiation by chemotherapy. alpha v reacted with 18 specimens and beta 3 with 12, without strict relation with the stage of the disease and/or its degree of differentiation; 9 well-differentiated specimens expressed the beta 4 chain; only 4 well-differentiated specimens expressed the alpha 4 chain. The 4 specimens which lacked alpha 1-beta 1 or alpha 3-beta 1 expression had n-myc amplification, whereas those which expressed either alpha 4, beta 4, beta 3 or alpha v had no amplification. Furthermore, the expression of the 3 heterodimers alpha 4-beta 1, alpha v-beta 3 and alpha 6-beta 4 was essentially observed on primary tumors which developed in the mediastinum. The expression of alpha 2-beta 1 and alpha 6-beta 1 was observed on both n-myc-positive and -negative specimens. beta 1 and alpha 3 were diffusely expressed on all counterparts of these tumors, from undifferentiated neuroblasts to ganglion and Schwann cells. The alpha 1 chain reacted with undifferentiated and intermediate neuroblasts as well as with Schwann cells, but ganglion cells were negative. alpha 2 and alpha 6 chains were negative on undifferentiated neuroblasts, variably expressed on intermediate neuroblasts, and restricted to Schwann cells in ganglioneuroma. The expression of alpha 4 and beta 4 was restricted to Schwann cells. alpha v and beta 3 occasionally reacted with undifferentiated and intermediate neuroblasts; alpha v was strongly positive on Schwann cells but negative on ganglion cells, whereas beta 3 was positive on both neuronal and non-neuronal populations.

Ganglioneuroma↗

Exploratory causal modeling in epidemiology: are all factors created equal?

The purpose of this study was to demonstrate the consequences of analyzing sequentially caused relationships with models assuming equally proximate causation. Monte Carlo simulations of data with well defined causations were performed. The logistic modeling approach was strongly misleading if a distant causal factor was treated as a factor being equally distant to the outcome as a proximal causal factor. In contrast, simple pathway analysis was able to correctly identify the true causation. In causal pathways, the relative risk of an intermediate cause with respect to the outcome needs to have a certain magnitude for the effect of the distant variable to be passed on. The results further show that the true relative risk of the distant variable is not dependent on its baseline prevalence. In contrast, the prevalence of the intermediate variable must be small enough to carry the influence of the distant variable through the causal chain. Practical epidemiologic exploration of etiological factors is presently dominated by stepwise multiple regression. This type of exploration is not model free but is often intuitively based on the structural assumption of equal proximity of all potential factors to the outcome. Equal proximity, however, is not likely in many etiologies, especially not if the causal factors under consideration are of different quality, like psychological and biological factors. In cases of causal pathways with some factors more distant and others more proximal to the outcome, the former tend to be dismissed by equal proximity modeling. Upstream exploration of more distant etiological factors is hindered by endemic stepwise multiple regression modeling, treating all variables as being equal in proximity to the outcome.

Confounding Factors, Epidemiologic↗

Grading of ovarian carcinomas.

Grading of ovarian carcinomas can have important implications for therapeutic decisions, in particular in International Federation of Gynecology and Obstetrics (FIGO) stage I. However, there are no universally accepted grading guidelines for this type of cancer. We applied the grading system suggested by Shimizu et al. (1) to a series of ovarian carcinomas from a single institution to evaluate its prognostic significance in relation to other predictive factors. One hundred ninety-two cases of ovarian carcinomas were studied, including all major histologic types. The histologic slides were evaluated with regard to architecture (glandular = 1 point, papillary = 2 points, solid = 3 points), nuclear pleomorphism (nuclear variability < or = 2:1 = 1 point, intermediate nuclei = 2 points, nuclear variability > or = 4:1 = 3 points), and mitotic activity per 10 high-power fields using objective 40x, ocular 10x/20 (0-7 mitoses = 1 point, 8-18 mitoses = 2 points, > or = 9 mitoses = 3 points). Carcinomas with a total score of 3-5 points were designated as grade I, 6-7 points were designated as grade II, and 8-9 points were designated as grade III. Kaplan-Meier curves showed the following 5-year survival rates: grade I (n = 42) 88%, grade II (n = 98) 60%, grade III (n = 52) 38% (p < 0.0001); stage I 90%, stage II 60%, stage III 38%, stage IV 10% (p < 0.0001); residual disease < or = 2 cm 67% and > or = 2 cm 27% (p < 0.0001). Multivariate Cox analysis revealed that grade (p < 0.0002), as well as nuclear pleomorphism alone (p < 0.0001), both provided statistically significant independent prognostic information. Our observations showed that the grading system used can be easily applied to all histologic types of ovarian carcinomas yielding prognostically relevant information and can be incorporated into routine diagnostic practice.

Adenocarcinoma, Clear Cell↗

Standards in behavioral teratology testing: test variability and sensitivity.

Regulatory guidelines have produced a need to develop behavioral screening techniques to accompany teratology and reproduction testing. In the repeated use of a provisional test battery, we have found that conclusions about the behavioral teratogenic potential of test compounds are most likely to be revealed using tests having intermediate levels of variability. The results obtained from examining animals exposed developmentally to brominated vegetable oil (BVO as 2.0, 1.0, 0.5, or 0.25 percent of the diet) and comparisons of the tests' coefficients of variation, offer an empirical example of this concept. Preweaning tests of locomotion and reflex development demonstrated numerous instances of developmental delay in the BVO-treated subjects, but postweaning tests revealed few abnormalities. Behavioral testing revealed functional deficits from BVO administration at doses lower than those which have adverse effects on reproduction. Examination of the tests' variability by using coefficients of variation as a comparative index, disclosed that the postweaning test variability was almost twice that of the preweaning tests. Thus, the lack of effects of BVO on most of the postweaning tests should not be conclusively interpreted as indicative of recovery of function, because this pattern is equally likely to have resulted from the lower sensitivity of these tests. An acceptable standard for future behavioral teratology screening requires a close examination of test variability, as it appears to be an important element in the sensitivity and, hence, the interpretation of such procedures.

Animals↗

Genetic variability of the mouse hepatoma cells MH-22a revealed by RAPD-PCR-fingerprinting under different conditions of cultivation.

AIM: to study genetic variability in clonal lines of the mouse hepatoma MH-22a and the dependence of the capability of different clonal line cells for differentiation on the amount of genetic disturbances revealed by the RAPD-PCR method. METHODS: The hepatoma MH-22a and its ten clonal lines were transplanted into subcutaneous connective tissue (SCT) and the eye anterior chamber (EAC) by injection of the cells to syngenic C3HA mice. The growth of transplants was checked in 15-20 days after transplantation. The tumors were fixed in neutral paraformaldehyde (10%), passed through ethanol of increasing concentrations, embedded in paraffin and stained by hematoxiline and eosine and Van Gisone. The genetic heterogeneity in the hepatoma cell population MH-22a and its clonal lines in vitro and in vivo was revealed by random amplified polymorphic DNA (RAPD-PCR). For the estimation of genetic variability revealed in the fingerprints was used the genetic variability index (GVI), based on the Bootstrep and Mikulinskaya's statistic programme. RESULTS: The comparative analysis of the genetic structure of the clonal line populations in vitro and in vivo has revealed that the amount of clones with the high, intermediate, and low variability is approximately the same in both cases. It was also shown that GVI in various clonal lines in vitro correlated with their vital ability: the clones yielding clone lines had the lowest GVI. The same GVI value was found in the clonal lines proliferated in the EAC regardless of their capability for differentiation. Intraclonal analysis has shown that the highest values of changes revealed on fingerprints of the amplification of DNA products do not prevent from differentiation of tumor hepatoma cells in the EAC. CONCLUSION: These data allow concluding that the mouse hepatoma cells MH-22a can preserve ability for differentiation in spite of significant changes in their genome.

Animals↗

Sleep laboratory study on single and repeated dose effects of paroxetine, alprazolam and their combination in healthy young volunteers.

AIMS: To evaluate the potential interaction of 20 mg paroxetine and 1 mg alprazolam (early morning once-daily administration) on polysomnographic (PSG) sleep and subjective sleep and awakening quality, both after a single intake and after reaching a steady-state concentration. METHODS: Twenty-two (11 for the PSG) healthy young volunteers of both sexes with no history of sleep disturbances (Pittsburgh Sleep Quality Index <5) participated in a double-blind, double-dummy, placebo-controlled, repeated-dose, 4-period, cross-over study. All volunteers received all 4 treatment sequences: paroxetine-alprazolam placebo (PAP); paroxetine placebo-alprazolam (PPA); paroxetine-alprazolam (PA), and paroxetine placebo-alprazolam placebo (PLA), in a randomized order. Each treatment was administered over 15 consecutive days, with a treatment-free interval of 7 days prior to the subsequent study period. In each experimental period, one PSG sleep study was performed on the 1st night (single-dose effects) and another study was performed on the 15th night (repeated-dose effects). Additionally, two other PSG studies were assessed: an adaptation recording, and a control night recording. All-night PSG recordings were obtained following standard procedures. Each 30-second period was scored according to the criteria of Rechtschaffen and Kales by means of an automatic sleep analysis system: Somnolyzer 24x7. A self-rating scale for sleep and awakening quality and early morning behavior was completed no later than 15 min after awakening over the 15 days of each experimental intervention. General lineal models (treatment/time) were applied separately to each variable. RESULTS: (1) No significant effects were observed in any sleep variables when control nights were compared with the 1st night with PLA. (2) Sleep continuity: After PAP a clear awakening effect was seen both in the first and second evaluations, mainly in wake time, movement time, number of awakenings and stage-1 duration. After PPA an evident hypnotic effect was observed on night 1. This effect was mainly observed in maintenance variables and slightly in sleep initiation variables; it had decreased by night 15. After PA an intermediate behavior in the variables related to sleep continuity was seen, highlighting the absence of the tolerance phenomenon observed when PPA was administered alone. (3) Sleep architecture: The most important effects in REM sleep were observed after PAP; an increase in REM latency and decreases in REM sleep. PAP also induced decreases in the number of non-REM and REM periods and increases in the average duration of non-REM periods and sleep cycles. PA presented a similar pattern to PAP, and PPA similar to PLA. In relation to non-REM sleep, PA showed more stage-2 and less slow-wave sleep (SWS). (4) Subjective perception: No significant differences were observed between treatments while they were being taken, but impairments in subjective sleep quality, awaking quality, latency and efficiency were seen, mainly after PA but also after PPA discontinuations. CONCLUSION: The combination of PAP and PPA presented an intermediate pattern in relation to sleep continuity, with less awaking effect than PAP alone and less hypnotic effect than PPA alone, and without developing tolerance. The PAP and PPA combination also showed a similar effect to PAP on REM sleep and was the treatment with the longest stage 2 and shortest SWS. No subjective sleep and awakening effects were seen during drug intake but subjective withdrawal reports were seen after abrupt interruption. The high agreement rate for the epoch-by-epoch comparison between automatic and human scoring confirms the validity of the Somnolyzer 24x7 and thus facilitates sleep studies in neuropsychopharmacological research.

Adult↗

A novel microdissection and genotyping of follicular-derived thyroid tumors to predict aggressiveness.

Distinguishing thyroid follicular adenoma from minimally invasive or encapsulated angioinvasive carcinoma can be diagnostically challenging. In some cases, tumors are distorted, fragmented, or stripped of their capsule, and a definitive diagnosis becomes nearly impossible. In other cases, the foci of capsular and/or vascular invasion are subtle, thus making the diagnosis of carcinoma difficult. We developed a microdissection genotyping assay for assessing a panel of tumor-suppressor genes for loss of heterozygosity mutations. The frequency of allelic loss (FAL) in follicular-derived neoplasms correlates with the histologic aggressiveness of the tumor. Furthermore, we calculated the amount of genetic heterogeneity within each tumor, as a second important measure of a tumor's ability for clonal expansion and a surrogate marker for its malignant potential. The follicular adenomas had a low FAL (average 9%) and low intratumoral heterogeneity (5% variability). The minimally invasive and encapsulated angioinvasive carcinomas had an intermediate FAL (average 30%) and intermediate intratumoral heterogeneity (10% variability). The widely invasive carcinomas had a high FAL (average 53%) and high intratumoral heterogeneity (24% variability). Although a larger retrospective study is needed to correlate genotyping studies with patient outcome and prognosis, our results indicate that performing a mutational genotyping assay can stratify tumors into the histologically well-defined categories of adenomas, minimally invasive/angioinvasive carcinomas, and widely invasive follicular carcinomas.

Adenoma↗

Enhancing the flexibility and adaptability of the DARC structural representation for computer-aided drug design.

Noticeable progress has been achieved in the determination of dynamic topochromatic variables for the structural representation of compounds and their situation in a given population. These independent structural variables can be further combined into more complex variables. Their contributions to the evolution of an associated property can therefore be evaluated with certainty. The risk of having correlated variables is avoided while the structural description remains exhaustive. In order to enhance the interpretative ability of the QSAR model, one or several physicochemical properties can be taken with these structural parameters as explanatory variables. Typically, partition coefficients, 3-D and quantum mechanical data are used for this purpose. The structural aspects not taken into account by the physicochemical parameters are reflected in the remaining topochromatic variables. The use of these new concepts is presented in a study of carbazole mutagenicity. The model explains 99% of the total variance with one external property and four additional topochromatic variables. The modulation of the heat of formation of an intermediate by two topochromatic variables suggests a much more precise interpretation than a simple combination of the usual external variables.

Animals↗

Etiology of common acquired melanocytic nevi: constitutional variables, sun exposure, and diet.

Associations were sought between prevalence of nevi on the arms and other variables in controls from a case-control study of cutaneous malignant melanoma. The prevalence of nevi was higher in women than men, fell with age up to about 35 years of age, and was low in those born outside Australia. Among pigmentary characteristics, there was strong evidence only of an association with skin color of the upper inner arm. The highest prevalence of nevi was in those with skin of intermediate darkness. Peak prevalence of nevi was also seen in intermediate categories of variables indicating sun exposure, particularly mean annual hours of bright sunlight at places of residence when 10-24 years of age, total outdoor exposure time per week in the summer at 10-24 years of age, and usual summer suntan on the arms in the last 10 years. These dose-effect patterns may indicate conflicting effects of sun exposure on appearance and disappearance of nevi. The protective effect of birthplace outside Australia appeared to be due to the corresponding low mean annual hours of bright sunlight at places of residence when 10-24 years of age. The prevalence of nevi was comparatively lower in those who drank alcohol and in those who had average or high daily intakes of retinol. These associations were not explained by those of any of the other variables.

Adolescent↗

Effects of additional starch or fat in late-gestating high nonstarch polysaccharide diets on litter performance and glucose tolerance in sows.

The effects of feeding additional starch or fat from d 85 of gestation until parturition on litter performance and on glucose tolerance in sows that were fed a diet with a high level of fermentable nonstarch polysaccharides (NSP) were studied. The day after breeding, 141 multiparous sows were assigned to the experiment. At d 85 of gestation, sows were assigned to the treatments. Sows were fed 3.4 kg/d (as-fed basis) of a high-NSP diet or the same quantity of the high-NSP diet and an additional 360 g of starch (from wheat starch) daily, or the same quantity of the high-NSP diet and an additional 164 g of fat (from soybean oil) daily. During lactation, all sows were given free access to the same lactation diet. Approximately 1 wk before the expected time of parturition, an oral glucose tolerance test was performed in 38 randomly chosen sows by feeding pelleted glucose (3 g/kg BW0.75). Blood samples for glucose analyses were taken at -10, 10, 20, 30, 40, 50, 60, 70, 80, 90, 105, and 120 min after glucose was fed. The supply of additional dietary starch or fat did not increase piglet birth weight or total litter weight at birth. Sows that were fed the high-NSP diet had more (P = 0.097) live-born piglets and fewer (P = 0.084) stillborn piglets than did sows that were fed additional fat, whereas sows that were fed additional starch were intermediate for these variables. Piglet mortality after birth was not affected by dietary treatment. Body weight and backfat gains in the last month of gestation were higher for sows fed additional starch or fat than for sows fed the high-NSP diet (P < 0.001 and P = 0.017, respectively). Feed intake in lactation was greatest by sows fed the high-NSP diet, least by sows fed additional starch at the end of gestation, and intermediate by sows fed additional fat (P = 0.099). The differences in lactation feed intake did not result in differences in BW and backfat losses during lactation. Sows that were fed additional fat had the greatest glucose area under the curve (P = 0.044), indicating that these sows were less tolerant to glucose. In conclusion, feeding additional energy (starch or fat) in late-gestating sows that are fed a high-NSP diet did not increase litter weight at birth or piglet survival, but did increase maternal gain. Feeding sows additional energy from fat might induce glucose intolerance, whereas feeding sows additional energy from starch did not induce glucose intolerance.

Animals↗

[Family and psychosocial variables in the choice of university studies].

INTRODUCTION: Family order of the children and family size as well as other psychosocial variables on University of the Basque Country (UBC) students are compared in order to relate these data with the choice of type of university studies. METHODS: As a sample, we studied 6,013 students from the UBC in different careers and courses. Mean age was 20.26 years. The following instruments were used: a sociodemographic questionnaire, the Eysenck Personality Scale and Yllá Alexithymia Scale. All them were validated for our country. RESULTS: The presence of women was greater in all the career studies except for engineering where the proportion of men was greater. The data verify the relationship between being the youngest or intermediate child of a family of three or more children and studying Journalism and Fine Arts and that the first born of families of two or more children are more represented in Engineering. It is interesting that there are fewer only children in Medicine where children of families of three or more, both first-born as well as intermediate, go. These variables, as well as extraversion, neuroticism and alexithymia, were different in the different career studies. It was also observed that the female university students scored higher in the neuroticism scale and that the levels of Alexithymia were higher among the men. Further, relations were found between child birth order and family size and personality, in the sense that the Medical and Odontology careers presented lower scores in Alexithymia while the more technical careers such as Engineering are those that present a higher alexithymia. Medicine and Odontology, followed by Mathematics and Journalism, obtained the highest scores in neuroticism. Engineering students obtain the lowest neuroticism. The most extroverted students are those from Journalism, Chemistry, Economics and Odontology. CONCLUSIONS: The choice of university studies is associated to gender, birth order, family size and personality patterns. Personality variables are related to gender, birth order and family size.

Adult↗

Inter-observer variability in the measurement of body composition.

The inter-observer variation in simple bedside assessments of body composition has been evaluated in 12 healthy adult subjects (6 male and 6 female) by 6 observers. Systematic bias between observers was found to be evident in each of the basic measurements (except height) and in each of the estimates of body composition (except those derived from weight and height alone). The largest residual coefficients of variation (rCV) for the basic measurements were found for skinfold thickness (11-18 per cent for individual skinfold thicknesses, and 9 per cent for the sum of four skinfold thicknesses), and the lowest for weight (0.01 per cent for digital scales, and 0.05 per cent for beam balance) and height (0.4 per cent). The rCV for whole-body resistance (1.2 per cent), forearm resistance (5.4 per cent) and near infra-red interactance (optical density 1: 5.6 per cent and optical density 2: 6.2 per cent) measurements were found to have intermediate values. The variability in the estimate of body fat obtained by skinfold thickness (rCV = 4.6 per cent) and near infra-red interactance methods (rCV = 4.2 per cent) was found to be greater than that from the resistance method (rCV = 2.6 per cent) and by methods based on weight and height alone (rCV = 1.1 per cent). The variability in the estimate of fat-free mass showed the same trend as that for body fat, but the rCVs were less due to the greater mass of the fat-free body compared to body fat.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The variability and accurate assessment of microinflammation in haemodialysis patients.

BACKGROUND: Systemic microinflammation is correlated with atherosclerosis. It needs a reliable assessment. This study explores the temporal variations of three inflammatory indexes [C-reactive protein (CRP), serum amyloid A (SAA) and interleukin-6 (IL-6)] in a period free of clinical events and tests the reliability of their multiple measurements for the assessment of microinflammation in haemodialysis (HD) patients, a population at high risk of atherosclerotic cardiovascular disease. METHODS: For 4 months, serum CRP, SAA and IL-6 were measured in 29 HD patients during the weeks they were free of inflammatory clinical events (> or =12 measurements for each index in every patient). The components of the variance as well as the reliability of two to five measurements for each index, aimed at assessing microinflammation precisely, were computed. RESULTS: The median (interquartile range) of CRP was 2.3 (0.9-4.9) mg/l, of SAA 3.7 (2.1-9.3) mg/l and of IL-6 4.4 (2.2-7.7) pg/ml. Patients were approximately equally distributed between three groups of low, intermediate and high variability for each index. The contribution of intraindividual (biological) variation to the total of variance was 71.3%, 69.3% and 86.7% for CRP, SAA and IL-6, respectively (higher than in all other similar studies in healthy populations). Using two measurements, the estimated reliability was 57-68% for CRP in two-thirds of the patients (comparable with that found in healthy subjects) and 57% for SAA and IL-6 in only one-third of the patients. Increasing the number of measurements up to five did not change the reliability. CONCLUSIONS: Individual factors significantly influence the levels of inflammatory indexes in HD patients in periods free of inflammatory clinical events. The mean of two weekly CRP measurements, but not of SAA or IL-6, seems to assess microinflammation in most patients with a sufficient reliability.

Adult↗

Period doubling of calcium spike firing in a model of a Purkinje cell dendrite.

Recordings from cerebellar Purkinje cell dendrites have revealed that in response to sustained current injection, the cell firing pattern can move from tonic firing of Ca(2+) spikes to doublet firing and even to quadruplet firing or more complex firing. These firing patterns are not modified substantially if Na(+) currents are blocked. We show that the experimental results can be viewed as a slow transition of the neuronal dynamics through a period-doubling bifurcation. To further support this conclusion and to understand the underlying mechanism that leads to doublet firing, we develop and study a simple, one-compartment model of Purkinje cell dendrite. The neuron can also exhibit quadruplet and chaotic firing patterns that are similar to the firing patterns that some of the Purkinje cells exhibit experimentally. The effects of parameters such as temperature, applied current, and potassium reversal potential in the model resemble their effects in experiments. The model dynamics involve three time scales. Ca(2+)- dependent K(+) currents, with intermediate time scales, are responsible for the appearance of doublet firing, whereas a very slow hyperpolarizing current transfers the neuron from tonic to doublet firing. We use the fast-slow analysis to separate the effects of the three time scales. Fast-slow analysis of the neuronal dynamics, with the activation variable of the very slow, hyperpolarizing current considered as a parameter, reveals that the transitions occurs via a cascade of period-doubling bifurcations of the fast and intermediate subsystem as this slow variable increases. We carry out another analysis, with the Ca(2+) concentration considered as a parameter, to investigate the conditions for the generation of doublet firing in systems with one effective variable with intermediate time scale, in which the rest state of the fast subsystem is terminated by a saddle-node bifurcation. We find that the scenario of period doubling in these systems can occur only if (1) the time scale of the intermediate variable (here, the decay rate of the calcium concentration) is slow enough in comparison with the interspike interval of the tonic firing at the transition but is not too slow and (2) there is a biostability of the fast subsystem of the spike-generating variables.

Action Potentials↗

Mechanisms for the development of genetically variable mycorrhizal mycelia in the ectomycorrhizal fungus Laccaria bicolor.

An in vitro study investigated mechanisms for the development of genetically variable mycorrhizal mycelia for Laccaria bicolor. Seedlings of jack pine (Pinus banksiana) grown nonaseptically in an autoclaved soil substrate were given different L. bicolor inoculum treatments. These included (i) a dikaryotic mycelium genotype (D); (ii) D and basidiospores collected from one group of five sporophores (T1); (iii) D and basidiospores collected from 10 sporophores, two from each of five different groups (T5); (iv) T1 alone; (v) T5 alone; and (vi) a noninoculated control. Dikaryotic mycelial inoculum was provided at the time of sowing, while basidiospore inoculum was added at 10 weeks after seed germination. Sporophore formation was induced after 20 weeks of growth, and dikaryotic cultures were isolated from their tissue. Seedlings were harvested, and growth and mycorrhization were assessed. Levels of both were generally lower for T1-treated seedlings, compared with seedlings receiving D, while levels for T5-treated seedlings were intermediate. Sporophore genotype variability was assessed for inoculum treatments by using the isoenzymatic marker leucine aminopeptidase. The greatest genetic variability was seen with the basidiospore treatments T1 and T5, with up to four leucine aminopeptidase patterns per seedling. The mixed treatments D plus T1 and D plus T5 produced most frequently, but not exclusively, the inoculated dikaryon genotype. After isoenzyme results were assessed, variable sporophore isolates of mixed treatments were analyzed with randomly amplified polymorphic DNA and PCR mitochondrial DNA markers to determine if they were formed by dikaryon-monokaryon crosses between the inoculated dikaryon and monosporous mycelia.(ABSTRACT TRUNCATED AT 250 WORDS)

Agaricales↗