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Association of RAPD marker with linolenic acid concentration in the seed oil of rapeseed (Brassica napus L.).

The F2 progeny (64 individuals) from the cross between oilseed rape (Brassica napus L.) cultivar Topas and R4 (a low linolenic mutation line) was analyzed with 8 RFLPs and 34 RAPDs to discover a genetic tag for gene(s) affecting linolenic acid concentration. According to variance analysis (ANOVA), one RAPD marker (25a) was significantly associated with linolenic acid content; the linolenic acid concentration in the seeds of F2 individuals showing the marker (includes both homo- and hetero-zygotes) was 7.43 +/- 1.35% and in those lacking the marker was 5.70 +/- 1.52%. Marker 25a may be used to facilitate selection for fatty acid composition in future breeding programs of oilseed rape.

Base Sequence↗

Genome size variation in Hordeum spontaneum populations

Populations of wild barley, Hordeum spontaneum (C. Koch), originating from 10 ecologically and geographically different sites in Israel, were assessed for genome size. Measurements were obtained by flow cytometry using propidium iodide staining. Genome sizes ranged from 9.35 to 9.81 pg. Variance analysis indicated a significant difference between populations. Genome sizes were positively correlated with mean January temperature. Our results corroborate previous findings of intraspecific variation in genome size from different plant species. The positive correlations between climate and genome size suggest that the latter is adaptive and determined by natural selection.

Journal Article↗

Myocardial perfusion after angioplasty in patients suspected of having single-vessel coronary artery disease: improvement detected at rest-stress first-pass perfusion MR imaging--initial experience.

PURPOSE: To prospectively assess myocardial perfusion before and after successful intervention in patients suspected of having single-vessel coronary artery disease by using a steady-state free precession (SSFP) perfusion magnetic resonance (MR) imaging sequence. MATERIALS AND METHODS: Local ethics committee approval and informed consent were obtained. Rest-stress perfusion MR imaging studies were performed in 18 patients with coronary artery disease (12 men, six women; mean age, 58.6 years +/- 13.6 [standard deviation]; range, 30-79 years) at 1.5 T with a multisection saturation-recovery SSFP sequence and 0.025 mmol gadopentetate dimeglumine per kilogram of body weight. MR studies were performed before (n = 18), several days after (n = 18), and 8 months after (n = 10) coronary intervention. Nine patients underwent percutaneous transluminal coronary angioplasty (PTCA) alone, and nine patients underwent PTCA with stent placement. Myocardial perfusion reserve index (MPRI) was calculated by dividing results of myocardial perfusion at maximal vasodilation by results at rest. The standard for myocardial perfusion was technetium 99m tetrofosmin single photon emission computed tomography. Statistical significance was tested with univariate variance analysis and Student t tests. RESULTS: In the area of the stenosed vessel, MPRI was 1.04 +/- 0.24 before treatment and 2.18 +/- 0.57 several days afterward (P < .001). In remote areas, MPRI was 2.42 +/- 0.44. In the stent group, MPRI increased by 156%, from 0.99 +/- 0.20 before stent placement to 2.53 +/- 0.53 after (P < .001). Similarly, in the PTCA only group, MPRI increased by 72%, from 1.08 +/- 0.27 before PTCA to 1.87 +/- 0.39 after (P < .001). At follow-up in patients without recurring chest pain, MPRI was 2.14 +/- 0.37 in the area of the treated artery and 2.29 +/- 0.47 in remote areas (P = .06). CONCLUSION: The MPRI, derived from rest-stress examinations, can provide information on success of interventional procedures in stenosed coronary arteries.

Adult↗

Alpha-adrenoreceptor influences on liquid movements by in vitro lungs from fetal guinea pigs.

Lungs from near-term fetal guinea pigs (60 +/- 2 days of gestation) were supported in vitro for 3 h; lung liquid production was monitored by a dye-dilution method. Studies of 30 fetuses showed that untreated preparations produced fluid at 1.34 +/- 0.21 ml.h-1.kg body wt-1, but epinephrine at concentrations known at delivery (10(-8) and 10(-7) M) produced significant reductions or fluid reabsorption (analysis of variance, regression analysis); at high levels (10(-6) and 10(-5) M, epinephrine had no effect. Maximal responses from 10(-7) M epinephrine involved alpha-adrenoreceptors, since they were abolished by 10(-6) M phentolamine (alpha-antagonist) but were unaffected by 10(-6) M propranolol (beta-antagonist; n = 36). Activation was through alpha2-adrenoreceptors, since responses were abolished by 10(-4) M yohimbine (alpha-antagonist; n = 24) but were resistant to 10(-5) M prazosin (alpha 1-antagonist; n = 24). At high levels of epinephrine (10(-5) M), where responses did not normally occur, reductions in lung liquid production were large if prazosin was also present (n = 24), and increases were significant if yohimbine was included (n = 24). In guinea pigs, epinephrine appears to activate lung fluid reabsorption through alpha 2-adrenoreceptors; at high concentrations only, it can also increase production through alpha 1-adrenoreceptors. Therefore, species differences appear to exist.

Adrenergic alpha-1 Receptor Antagonists↗

Control of the subthalamic innervation of substantia nigra pars reticulata by D1 and D2 dopamine receptors.

The effects of activating dopaminergic D1 and D2 class receptors of the subthalamic projections that innervate the pars reticulata of the subtantia nigra (SNr) were explored in slices of the rat brain using the whole cell patch-clamp technique. Excitatory postsynaptic currents (EPSCs) that could be blocked by 6-cyano-7-nitroquinoxalene-2,3-dione and D-(-)-2-amino-5-phosphonopentanoic acid were evoked onto reticulata GABAergic projection neurons by local field stimulation inside the subthalamic nucleus in the presence of bicuculline. Bath application of (RS)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF-38393), a dopaminergic D1-class receptor agonist, increased evoked EPSCs by approximately 30% whereas the D2-class receptor agonist, trans-(-)-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo(3,4-g)quinoline (quinpirole), reduced EPSCs by approximately 25%. These apparently opposing actions were blocked by the specific D1- and D2-class receptor antagonists: R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetra-hydro-1H-3-benzazepinehydrochloride (SCH 23390) and S-(-)-5-amino-sulfonyl-N-[(1-ethyl-2-pyrrolidinyl)-methyl]-2-methoxybenzamide (sulpiride), respectively. Both effects were accompanied by changes in the paired-pulse ratio, indicative of a presynaptic site of action. The presynaptic location of dopamine receptors at the subthalamonigral projections was confirmed by mean-variance analysis. The effects of both SKF-38393 and quinpirole could be observed on terminals contacting the same postsynaptic neuron. Sulpiride and SCH 23390 enhanced and reduced the evoked EPSC, respectively, suggesting a constitutive receptor activation probably arising from endogenous dopamine. These data suggest that dopamine presynaptically modulates the subthalamic projection that targets GABAergic neurons of the SNr. Implications of this modulation for basal ganglia function are discussed.

Animals↗

A voltage-dependent and calcium-permeable ion channel in fused presynaptic terminals of Torpedo.

1. We used a preparation of fused presynaptic nerve terminals of Torpedo electromotor nerve and the patch-clamp technique for characterization of single ion channels. We report here of a large, nonselective ion channel which is highly voltage dependent. 2. The slope conductance of the I-V relation was estimated by either direct measurement of the single-channel current amplitude at different voltages (850 +/- 18 pS (SE); n = 9) or by variance analysis (834 +/- 23 pS; n = 5). 3. The voltage dependence was examined in three ways. At steady-state DC voltage conditions, NPo (the open probability times the number of channels in the patch) was estimated. At potentials < 0 mV, the probability of the channel to open is negligible and increases dramatically, within a very narrow voltage range, to > 50% at +8 mV (n = 8). 4. In pulse experiments, the activation time delay is shorter as the voltage step reaches more positive values. The mean time for half activation (T1/2) decreases from 15 ms at +10 mV to 4 ms at +30 mV (n = 5). 5. Ensemble currents exhibit rectification in response to voltage ramps at negative potentials (n = 10). 6. The channel was found to be nonselective. Its permeability to Na+, K+, Cl-, glutamate, Ba+2, and Ca+2, relative to Na+, was 1.00, 1.00, 1.22, 1.07, 0.85, and 0.62, respectively. 7. Based on the transport number of calcium, the calculated driving force, and the mean channel open time, we estimated the number of calcium ions entering the nerve terminal upon depolarization. This number is not substantially different from the number of ions entering through voltage-dependent, calcium-selective channels in other cells. 8. We speculate that this nonselective ion channel, may serve as a calcium entry route into the nerve terminal and hence be involved in transmitter release.

Animals↗

Afterhyperpolarization current in myenteric neurons of the guinea pig duodenum.

Whole cell patch and cell-attached recordings were obtained from neurons in intact ganglia of the myenteric plexus of the guinea pig duodenum. Two classes of neuron were identified electrophysiologically: phasically firing AH neurons that had a pronounced slow afterhyperpolarization (AHP) and tonically firing S neurons that lacked a slow AHP. We investigated the properties of the slow AHP and the underlying current (I(AHP)) to address the roles of Ca(2+) entry and Ca(2+) release in the AHP and the characteristics of the K(+) channels that are activated. AH neurons had a resting potential of -54 mV and the AHP, which followed a volley of three suprathreshold depolarizing current pulses delivered at 50 Hz through the pipette, averaged 11 mV at its peak, which occurred 0.5-1 s following the stimulus. The duration of these AHPs averaged 7 s. Under voltage-clamp conditions, I(AHP)'s were recorded at holding potentials of -50 to -65 mV, following brief depolarization of AH neurons (20-100 ms) to positive potentials (+35 to +50 mV). The null potential of the I(AHP) at its peak was -89 mV. The AHP and I(AHP) were largely blocked by omega-conotoxin GVIA (0.6-1 microM). Both events were markedly decreased by caffeine (2-5 mM) and by ryanodine (10-20 microM) added to the bathing solution. Pharmacological suppression of the I(AHP) with TEA (20 mM) or charybdotoxin (50-100 nM) unmasked an early transient inward current at -55 mV following step depolarization that reversed at -34 mV and was inhibited by niflumic acid (50-100 microM). Mean-variance analysis performed on the decay of the I(AHP) revealed that the AHP K(+) channels have a mean chord conductance of ~10 pS, and there are ~4,000 per AH neuron. Spectral analysis showed that the AHP channels have a mean open dwell time of 2.8 ms. Cell-attached patch recordings from AH neurons confirmed that the channels that open following action currents have a small unitary conductance (10-17 pS) and open with a high probability (</=0.5) within the first 2 s following an action potential. These results indicate that the AHP is largely a consequence of Ca(2+) entry through omega-conotoxin GVIA-sensitive Ca(2+) channels during the action potential, Ca(2+)-triggered Ca(2+) release from caffeine-sensitive stores and the opening of Ca(2+)-sensitive small-conductance K(+) channels.

Action Potentials↗

Positive allosteric modulators of AMPA receptors reduce proton-induced receptor desensitization in rat hippocampal neurons.

Whole-cell or outside-out patch recordings were used to investigate the effects of protons and positive modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on the desensitization of glutamate-evoked AMPA receptor currents in isolated hippocampal CA1 neurons. Protons inhibited glutamate-evoked currents (IC(50) of 6.2 pH units) but also enhanced the apparent rate and extent of AMPA receptor desensitization. The proton-induced enhancement of desensitization could not be attributed to a reduction in the rate of recovery from desensitization or to a change in the kinetics of deactivation. Non-stationary variance analysis indicated that protons reduced maximum open probability without changing the conductance of AMPA channels. The positive modulators of AMPA receptor desensitization, cyclothiazide and GT-21-005 (an organic nitrate), reduced the proton sensitivity of AMPA receptor desensitization, which suggests that they interact with protons to diminish desensitization. In contrast, the effects of wheat germ agglutinin and aniracetam on AMPA receptor desensitization were independent of pH. These results demonstrate that a reduction in the proton sensitivity of receptor desensitization contributes to the mechanism of action of some positive modulators of AMPA receptors.

Allosteric Regulation↗

Gadolinium reduces AMPA receptor desensitization and deactivation in hippocampal neurons.

The actions of the trivalent cation Gd(3+) on whole cell AMPA receptor-mediated currents were studied in isolated hippocampal neurons, in nucleated or outside-out patches taken from cultured hippocampal neurons, and on miniature excitatory postsynaptic currents (mEPSCs) recorded in cultured hippocampal neurons. Glutamate, AMPA, or kainate was employed to activate AMPA receptors. Applications of relatively low concentrations of Gd(3+) (0.1-10 microM) substantially enhanced steady-state whole cell glutamate and kainate-evoked currents without altering peak currents, suggesting that desensitization was reduced. However, higher concentrations (>30 microM) depressed steady-state currents, indicating an underlying inhibition of channel activity. Lower concentrations of Gd(3+) also increased the potency of peak glutamate-evoked currents without altering that of steady-state currents. An ultrafast perfusion system and nucleated patches were then used to better resolve peak glutamate-evoked currents. Low concentrations of Gd(3+) reduced peak currents, enhanced steady-state currents, and slowed the onset of desensitization, providing further evidence that this cation reduces desensitization. In the presence of cyclothiazide, a compound that blocks desensitization, a low concentration Gd(3+) inhibited both peak and steady-state currents, indicating that Gd(3+) both reduces desensitization and inhibits these currents. Gd(3+) reduced the probability of channel opening at the peak of the currents but did not alter the single channel conductance calculated using nonstationary variance analysis. Recovery from desensitization was enhanced, and glutamate-evoked current activation and deactivation were slowed by Gd(3+). The Gd(3+)-induced reduction in desensitization did not require the presence of the GluR2 subunit as this effect was seen in hippocampal neurons from GluR2 null-mutant mice. Gd(3+) reduced the time course of decay of mEPSCs perhaps as a consequence of its slowing of AMPA receptor deactivation although an increase in the frequency of mEPSCs also suggested enhanced presynaptic release of transmitter. These results demonstrate that Gd(3+) potently reduces AMPA receptor desensitization and mimics a number of the properties of the positive modulators of AMPA receptor desensitization such as cyclothiazide.

Animals↗

A genome scan for QTL influencing milk production and health traits in dairy cattle.

A genome scan was conducted in the North American Holstein-Friesian population for quantitative trait loci (QTL) affecting production and health traits using the granddaughter design. Resource families consisted of 1,068 sons of eight elite sires. Genome coverage was estimated to be 2,551 cM (85%) for 174 genotyped markers. Each marker was tested for effects on milk yield, fat yield, protein yield, fat percentage, protein percentage, somatic cell score, and productive herd life using analysis of variance. Joint analysis of all families identified marker effects on 11 chromosomes that exceeded the genomewide, suggestive, or nominal significance threshold for QTL effects. Large marker effects on fat percentage were found on chromosomes 3 and 14, and multimarker regression analysis was used to refine the position of these QTL. Half-sibling families from Israeli Holstein dairy herds were used in a daughter design to confirm the presence of the QTL for fat percentage on chromosome 14. The QTL identified in this study may be useful for marker-assisted selection and for selection of a refined set of candidate genes affecting these traits.

Animals↗

[Antibiotic resistance transformation in community-acquired urinary infections].

OBJECTIVE: To detect the prevalence of uropathogens in community-acquired urinary tract infection in our environment, and the degree of sensitivity to antibiotics used as empirical treatment. PATIENTS AND METHOD: Retrospective longitudinal study on 16,392 consecutive urine cultures collected in the emergency department of Hospital del Mar, between January 1997 and December 2001. Resistance rates were compared through variance analysis. RESULTS: 8,743 urine cultures with significant count were obtained. 6,062 Escherichia coli (69.3%), 517 Proteus mirabilis (5.9%) and 390 Klebsiella pneumoniae (4.5%) were identified. Escherichia coli showed progressive growth rate and significant resistances to most of antibiotics evaluated, especially to quinolones which came close to 30%. Fosfomycin showed the least resistance rate (0.9%) and remained stable along the years studied. CONCLUSIONS: These results suggest that higher rate of resistance to quinolones does not advise its use as empirical in community-acquired urinary tract infection treatment in our environment. According to our experience, fosfomycin can be an excellent option for cystitis treatment in patients without risk factors, while for the treatment of parenchymatous urinary tract infection, complicated urinary tract infections, and urinary tract infections associated to risk factors, preference could be second or third generation oral cephalosporins, or amoxicillin-clavulanic acid.

Adolescent↗

[Women's satisfaction with pregnancy follow-up. Differences among healthcare levels].

OBJECTIVES: To determine women's satisfaction with pregnancy follow-up and to evaluate possible differences among healthcare levels. METHODS: Cross-sectional study in women who had given birth in the University Hospital of Salamanca (Spain) between November 2002 and April 2003. Satisfaction was measured by a self-completed questionnaire after delivery. The questionnaire contained 28 items, with five optional answers (1, not satisfied; 5, highly satisfied), distributed in four dimensions: accessibility, equipment, organization of the consultation, and professional competence. Social demographic and healthcare-related variables were also included. Student's t-test, variance analysis, Pearson's correlation coefficient and logistic regression were used to study the association between these variables and satisfaction. RESULTS: A total of 27.1% of pregnancies were followed-up in primary care. The mean global satisfaction was 3.92 (95% CI, 3.88-3.97), and satisfaction was higher in women followed-up in primary care than those followed-up in specialized care. All dimensions obtained a global satisfaction of more than 3; "accessibility" received the worst score and "professional competence" the highest. The factors significantly associated with satisfaction were age, educational level, the presence of risk factors and complications, and the possibility of choosing the physician. CONCLUSIONS: General satisfaction was good. Because satisfaction was higher in women followed-up in primary care than in those followed-up in specialized care, pregnancy follow-up at this level of healthcare should be supported.

Adult↗

[Factors determining the duration of temporary disability and return to work in a health district of Galicia].

OBJECTIVE: To determine the factors associated with the incidence and duration of temporary work incapacity (TWI) in a health district. DESIGN: Descriptive and retrospective study. SETTING: South health district of the province of Lugo, Spain. PARTICIPANTS: A random sample of 1513 cases was selected among the total of episodes of TWI, during 3 years period. MAIN MEASURES: The main factors analyzed are, on the one hand, the socio-demographic characteristics of the patient, his or her social security (SS) scheme, diagnosis that justifies the TWD, and the prescription date; and, on the other hand, the age, sex, specialised training, time in the post and years in practice of the physician who prescribes the TWI. The comparison of the means was carried out using variance analysis and the Kruskal-Wallis test. The relative effect of each variable on the probability of returning to the work was estimated through Cox regression models. RESULTS: The mean duration of the episodes of TWI was of 74+/-103 days. The most frequent diagnoses were those of the bones-muscles and joints (BMAJ), injuries and poisonings (IAP), and respiratory diseases (RD). The probability of returning to work is reduced with the increase of the age, with agrarian and autonomous SS affiliates, with diagnoses of mental disease or diagnoses of the circulatory system, and in cases prescribed by older doctors or less time in the post. CONCLUSIONS: The mean duration of the episodes of TWD is higher than that of other Spanish studies. The most influential factors in the return to work are the age of the patient, the SS scheme and the diagnosed illness.

Adult↗

Evaluation of nasal mucociliary functions with rhinoscintigraphy in coal workers' pneumoconiosis.

OBJECTIVE: To compare nasal mucociliary clearance (NMC) functions in coal workers with pneumoconiosis, coal workers without pneumoconiosis and healthy controls by using technetium-99m-labeled macroaggregated albumin rhinoscintigraphy. METHODS: Sixty-five of the 86 coal workers were clinically documented as suffering from coal workers' pneumoconiosis (CWP group). CWP workers were divided into two groups according to smoking status: 44 smokers (CWP-S) and 21 nonsmokers (CWP-NS). Twenty-one workers without pneumoconiosis (NCWP group) were similarly divided into two groups: 12 smokers (NCWP-S) and 9 nonsmokers (NCWP-NS). Thirty-three healthy male volunteers were selected for the control group [15 smokers (control-S), 18 nonsmokers (control-NS)]. The half-time (t1/2) value for the clearance of the radiopharmaceutical was calculated for each patient. RESULTS: Mean t1/2 values for CWP-S, CWP-NS, NCWP-S, NCWP-NS, control-S and control-NS were 25.10 +/- 7.75, 10.97 +/- 3.24, 14.68 +/- 4.98, 9.17 +/- 3.71, 19.15 +/- 5.04 and 15.08 +/- 5.11, respectively (p < 0.001, Kruskal-Wallis variance analysis). Further, mean t1/2 values of smokers versus nonsmokers in CWP, NCWP and control groups were compared, and it was found that although smoking prolonged nasal transport time in all three groups, the difference was significant only in the CWP group (p < 0.001, p < 0.023 and p < 0.027, respectively, Bonferroni-adjusted Mann-Whitney test). CONCLUSION: Our findings demonstrated a synergistic detrimental effect of smoking with coal dust exposure on nasal transport time.

Adult↗

Fractional urea clearance in continuous ambulatory peritoneal dialysis: effects of volume disturbances.

The effects of volume disturbances on the KT/V were investigated prospectively in 133 consecutive urea clearance studies on patients on continuous ambulatory peritoneal dialysis (CAPD). Four subjects (group A) had fluid loss (actual weight < dry weight), 57 (group B) were studied on the basis of their dry weight, 58 (group C) had moderate fluid excess (0.5% of dry weight), and 14 patients (group D) had severe fluid excess (> 5% of dry weight). The KT/V was calculated on the basis of dry weight and actual weight with V obtained from the Watson anthropometric formulae which were applied either uncorrected or with a correction for changes in body water from dry weight conditions. The groups compared by variance analysis. The following weekly KT/V estimates were obtained: (1) using dry weight V: group A 1.81 +/- 0.17, group B 2.0 +/- 0.59, group C 1.79 +/- 0.46, group D 1.85 +/- 0.37 (no difference between groups); (2) using uncorrected actual weight V: group A 1.85 +/- 0.15, group B 2.05 +/- 0.59, group C 1.77 +/- 0.45, group D 1.78 +/- 0.37 (group B had a higher KT/V than group C, p < 0.05), and (3) using corrected actual weight V: group A 1.93 +/- 0.14, group B 2.05 +/- 0.59, group C 1.70 +/- 0.43, group D 1.63 +/- 0.36, (group B had a higher KT/V than either group C or group D, both at p < 0.01). In CAPD, fluid deficit is rare and causes a small increase in KT/V, whereas fluid retention is frequent and causes a decrease in KT/V. This decrease is pronounced in patients with severe fluid excess. The uncorrected Watson formulae underestimate V and, consequently, overestimate KT/V in CAPD patients with fluid excess.

Aged↗

Algorithm for short-term prescription of phenprocoumon.

Data from the start of anticoagulation therapy using the coumarin derivative phenprocoumon were obtained retrospectively for 101 patients, and the correct long-term maintenance dose (MD) of the drug was determined. The average loading dose was 23.2 +/- 7.8 mg and the average MD 2.14 +/- 0.99 mg. The physician's prescription on discharge tended to underestimate the true MD by 0.29 +/- 0.64 mg. Significant positive correlations with MD were noted for loading dose and weight and negative correlations for age, serum creatinine, initial prothrombin ratio, and length of treatment pause (days) for patients receiving an excessive loading dose. Using stepwise variance analysis, an algorithm was obtained that predicted the MD: MD = -0.7 + loading dose/10 - treatment pause/7 - age/60 + initial prothrombin ratio. The accuracy (0.02 +/- 0.54 mg) was similar to that of the discharging physician. The algorithm required an average observation period of 5.4 days and the physician's estimate 12.4 days. It is suggested that the use of the algorithm would lead to shorter hospitalization without loss of treatment accuracy.

4-Hydroxycoumarins↗

Genetic variation in white matter hyperintensity volume in the Framingham Study.

BACKGROUND AND PURPOSE: In a previous study of normal elderly male twins, the heritability of quantitative white matter hyperintensity (WMH) volume has been estimated to be high (0.73). We investigated heritability of WMH in a family-based sample of the Framingham Heart Study for sex differences and the impact of age. METHODS: Brain magnetic resonance scans were performed on 2012 individuals in the cohort and offspring of the Framingham study. This report was limited to 1330 stroke-free and dementia-free members (mean age 61.0 years) of the Framingham offspring. Individuals with a history of multiple sclerosis, stroke, dementia, or other neurological condition including traumatic brain injury were excluded from this analysis. WMH volume and total cranial volume (TCV) were quantified using a previously published algorithm. Because of extreme skewing, measures of WMH were log-transformed before analysis. Variance components methods were used to estimate heritability of WMH after adjusting for sex, age, age2, and TCV. RESULTS: In the full dataset, WMH heritability was 0.55 (P<0.0001). Heritability among women was 0.78 (P<0.0001) whereas heritability among men was 0.52 (P<0.0003). Heritability varied as average age increased, with a peak of 0.68 (P<0.0001) in individuals aged 55 or older. CONCLUSIONS: Using a family-based study design comprising generally healthy individuals, this study found high heritability of WMH overall and similar heritability for both men and women. In addition, the heritability of WMH remained high among individuals in whom the prevalence of cerebrovascular brain injury was generally low, suggesting that WMH is also likely to be an excellent genetic marker of brain aging.

Adult↗

Central compensation at short muscle range is differentially affected in cortical versus subcortical strokes.

BACKGROUND AND PURPOSE: The active force generated by a single muscle fiber is greatest in midrange. In healthy subjects, the reduced muscle force at short muscle length is partially compensated by modified patterns of muscle activation, probably central in origin. These patterns are presumed to be deficient after stroke. We examined the excitability muscle-length relation in stroke patients and healthy controls and hypothesized about its alteration in stroke patients. METHODS: Corticospinal excitability was assessed in 31 stroke patients (19 subcortical, 12 cortical) and 19 healthy volunteers by transcranial magnetic stimulation. We recorded the motor evoked potentials (MEPs) simultaneously from the biceps brachii and the triceps brachii muscles at 0 degrees, 20 degrees, 40 degrees, 60 degrees, 80 degrees, 100 degrees, and 120 degrees degrees of elbow flexion (0 degrees being full elbow extension). RESULTS: Normal subjects revealed a significant increase in MEP amplitudes at shortened muscle lengths for both the flexor and extensor muscles (P<0.001). Multivariate variance analysis revealed that the MEP-angle curves of cortical stroke patients were significantly different from those of the control group for both muscles, lacking an increase of corticospinal excitability at short muscle length. Yet the MEP-angle curves for the subcortical stroke patients did not show a statistically significant difference from the control group for either muscle. CONCLUSIONS: Cortical and subcortical strokes differentially affect the corticospinal excitability muscle-length relation. This may account for the reported disproportionate decrease in muscle strength at shortened range after stroke.

Adaptation, Physiological↗