A majority rule approach for region-of-interest-guided streamline fiber tractography.

Hand-drawn gray matter regions of interest (ROI) are often used to guide the estimation of white matter tractography, obtained from diffusion-weighted magnetic resonance imaging (DWI), in healthy and in patient populations. However, such ROIs are vulnerable to rater bias of the individual segmenting the ROIs, scan variability, and individual differences in neuroanatomy. In this report, a "majority rule" approach is introduced for ROI segmentation used to guide streamline tractography in white matter structures. DWI of one healthy participant was acquired in ten separate sessions using a 3 T scanner over the course of a month. Four raters identified ROIs within the left hemisphere [Cerebral Peduncle (CPED); Internal Capsule (IC); Hand Portion of the Motor Cortex, or Hand Bump, (HB)] using a group-established standard operating procedure for ROI definition to guide the estimation of streamline tracts within the corticospinal tract (CST). Each rater traced the ROIs twice for each scan session. The overlap of each rater's two ROIs was used to define a representative ROI for each rater. These ROIs were combined to create a "majority rules" ROI, in which the rule requires that each voxel is selected by at least three of four raters. Reproducibility for ROIs and CST segmentations were analyzed with the Dice Similarity Coefficient (DSC). Intra-rater reliability for each ROI was high (DSCs ≥ 0.83). Inter-rater reliability was moderate to adequate (DSC range 0.54-0.75; lowest for IC). Using intersected majority rules ROIs, the resulting CST showed improved overlap (DSC = 0.82) in the estimated streamline tracks for the ten sessions. Despite high intra-rater reliability, there was lower inter-rater reliability consistent with the expectation of rater bias. Employing the majority rules method improved reliability in the overlap of the CST.

Accuracy of self-reported tobacco use status among hematopoietic SCT patients.

Tobacco use is a risk factor for adverse outcomes among hematopoietic SCT (HSCT) patients. Accurate identification of tobacco use offers a vital opportunity to treat this risk factor. The current study compared self-reported tobacco use status with serum cotinine levels among HSCT patients at the time of pre-transplant evaluation. A total of 444 participants completed both assessments; 44 participants (9.9%) were classified as tobacco users with serum cotinine concentrations >2 ng/mL vs 29 with self-reporting. Sensitivity and specificity of self-reporting were 65.9% and 100%, respectively. Positive and negative predictive values were 100% and 96.4%, respectively. Comparing tobacco use documented in the medical record with cotinine, sensitivity and specificity were 51.2% and 99.2%, respectively. Factors associated with tobacco use were male gender, single relationship status, less education and younger age. In summary, utilization of serum cotinine assays increased detection of tobacco use cases >50% over self-reporting. Results are discussed in the context of translation to care, including clinical and ethical implications, and current tobacco use treatment guidelines. When cotinine assays are not available, self-reporting of any tobacco use in the year before HSCT should trigger brief advice and cessation or relapse prevention counseling.

Methodical aspects of text testing in a driving simulator.

A test with 30 test persons was conducted in a driving simulator. The test was a concept exploration and comparison of existing user interaction technologies for text message handling with focus on traffic safety and experience (technology familiarity and learning effects). Focus was put on methodical aspects how to measure and how to analyze the data. Results show difficulties with the eye tracking system (calibration etc.) per se, and also include the subsequent raw data preparation. The physical setup in the car where found important for the test completion.

The impact of smoking on outcomes among patients undergoing hematopoietic SCT for the treatment of acute leukemia.

A paucity of research exists examining the potential impact of tobacco use on cancer treatment outcomes, especially among patients treated with hematopoietic SCT (HSCT). A retrospective cohort study design was used to examine the impact of smoking on duration of hospitalization and overall survival among 148 consecutive patients undergoing HSCT for treatment of acute leukemia from 1999 to 2005. Of the 148 patients, 15% reported current smoking, 30% former smoking, and 55% never used tobacco. Patients were followed for a median 3.5 years (interquartile range=2.1-5.5). Compared to no history of smoking, current smoking was associated with worse pre-HSCT pulmonary function tests (P<0.02 in each case), more days hospitalization (46.2 days versus 25.7 days, P=0.025), and poorer overall survival (hazard ratio (HR)=1.88; 95% CI 1.09-3.25). Results were similar after multivariate adjustment, although the association with overall survival attenuated slightly (HR=1.75; 95% CI 1.00-3.06). Current smoking appears to adversely affect the number of days hospitalized post HSCT and overall survival. Translational research focused on interventions to promote tobacco cessation may lead to improved HSCT outcomes.

Overexpression of hns in the plant growth-promoting bacterium Enterobacter cloacae UW5 increases root colonization.

AIMS: Plant growth-promoting rhizobacteria (PGPR) introduced into soil often do not compete effectively with indigenous micro-organisms for plant colonization. The aim of this study was to identify novel genes that are important for root colonization by the PGPR Enterobacter cloacae UW5. METHODS AND RESULTS: A library of transposon mutants of Ent. cloacae UW5 was screened for mutants with altered ability to colonize canola roots using a thermal asymmetric interlaced (TAIL)-PCR-based approach. A PCR fragment from one mutant was reproducibly amplified at greater levels from genomic DNA extracted from mutant pools recovered from seedling roots 6 days after seed inoculation compared to that from the cognate inoculum cultures. Competition assays confirmed that the purified mutant designated Ent. cloacae J28 outcompetes the wild-type strain on roots but not in liquid cultures. In Ent. cloacae J28, the transposon is inserted upstream of the hns gene. Quantitative RT-PCR showed that transposon insertion increased expression of hns on roots. CONCLUSIONS: These results indicate that increased expression of hns in Ent. cloacae enhances competitive colonization of roots. SIGNIFICANCE AND IMPACT OF THE STUDY: A better understanding of the genes involved in plant colonization will contribute to the development of PGPR that can compete more effectively in agricultural soils.

A physiology based inverse dynamic analysis of human gait: potential and perspectives.

One approach to compute the musculotendon forces that underlie human motion is to combine an inverse dynamic analysis with a static optimisation procedure. Although computationally efficient, this classical inverse approach fails to incorporate constraints imposed by muscle physiology. The present paper reports on a physiological inverse approach (PIA) that combines an inverse dynamic analysis with a dynamic optimisation procedure. This allows the incorporation of a full description of muscle activation and contraction dynamics, without loss of computational efficiency. A comparison of muscle excitations and MT-forces predicted by the classical and the PIA is presented for normal and pathological gait. Inclusion of muscle physiology primarily affects the rate of active muscle force build-up and decay and allows the estimation of passive muscle force. Consequently, it influences the onset and cessation of the predicted muscle excitations as well as the level of co-contraction.

Capacity to increase walking speed is limited by impaired hip and ankle power generation in lower functioning persons post-stroke.

It is well known that stroke patients walk with reduced speed, but their potential to increase walking speed can also be impaired and has not been thoroughly investigated. We hypothesized that failure to effectively recruit both hip flexor and ankle plantarflexor muscles of the paretic side limits the potential to increase walking speed in lower functioning hemiparetic subjects. To test this hypothesis, we measured gait kinematics and kinetics of 12 persons with hemiparesis following stroke at self-selected and fast walking conditions. Two groups were identified: (1) lower functioning subjects (n=6) who increased normalized walking speed from 0.52 leg lengths/s (ll/s, SEM: 0.04) to 0.72 ll/s (SEM: 0.03) and (2) higher functioning subjects (n=6) who increased walking speed from 0.88 ll/s (SEM: 0.04) to 1.4 ll/s (SEM 0.03). Changes in spatiotemporal parameters, joint kinematics and kinetics between self-selected and fast walking were compared to control subjects examined at matched walking speeds (0.35 ll/s (SEM: 0.03), 0.63 ll/s (SEM: 0.03), 0.92 ll/s (SEM: 0.04) and 1.4 ll/s (SEM: 0.04)). Similar to speed-matched controls, the higher functioning hemiparetic subjects increased paretic limb hip flexion power and ankle plantarflexion power to increase walking speed. The lower functioning hemiparetic subjects did not increase power generation at the hip or ankle to increase walking speed. This observation suggests that impaired ankle power generation combined with saturation of hip power generation limits the potential to increase walking speed in lower functioning hemiparetic subjects.

Does unilateral pedaling activate a rhythmic locomotor pattern in the nonpedaling leg in post-stroke hemiparesis?

Recent investigation in persons with clinically complete spinal cord injury has revealed that locomotor activity in one limb can activate rhythmic locomotor activity in the opposite limb. Although our previous research has demonstrated profound influences of the nonparetic limb on paretic limb motor activity poststroke, the potency of interlimb pathways for increasing recruitment of the paretic limb motor pattern is unknown. This experiment tested whether there is an increased propensity for rhythmic motor activity in one limb (pedaling limb) to induce rhythmic motor activity in the opposite limb (test limb) in persons poststroke. Forty-nine subjects with chronic poststroke hemiparesis and twenty controls pedaled against a constant mechanical load with their pedaling leg while we recorded EMG and pedal forces from the test leg. For the experimental conditions, subjects were instructed to either pedal with their test leg (bilateral pedaling) or rest their test leg while it was either stationary or moved anti-phased (unilateral pedaling). In persons poststroke, unilateral pedaling activated a complete pattern of rhythmic alternating muscle activity in the nonpedaling, test leg. This effect was most clearly demonstrated in the most severely impaired individuals. In most of the control subjects, unilateral pedaling activated some muscles in the nonpedaling leg weakly, if at all. We propose that, ipsilateral excitatory pathways associated with contralateral pedaling in control subjects are increasingly up-regulated in both legs in persons with hemiparesis as a function of increased hemiparetic severity. This enhancement of interlimb pathways may be of functional importance since contralateral pedaling induced a complete motor pattern of similar amplitude to the bilateral pattern in both the paretic and nonparetic leg of the subjects with severe hemiparesis.

Interlimb influences on paretic leg function in poststroke hemiparesis.

After stroke, paretic leg motor impairment is typically viewed as a unilateral control deficit. However, much of the neural circuitry controlling normal leg function is organized bilaterally to produce coordinated, task-specific activity in the two legs. Thus, as a result of contralesional neural control processes, paretic leg motor pattern generation may be substantially influenced by the nonparetic leg sensorimotor state during bilateral lower limb tasks. Accordingly, we investigated whether different paretic leg motor patterns are observed during mechanically equivalent bilateral and unilateral tasks and, if so, whether nonparetic leg participation improved or exacerbated paretic leg coordination deficits. A pedaling apparatus that mechanically decoupled the legs was used to present subjects with increasingly complex bi- and unilateral motor tasks: isometric force generation, discrete movement, and pedaling. Bilateral electromyographic and pedal force data were collected from 21 persons with chronic poststroke hemiparesis and 11 similarly aged controls. During isometric force generation and discrete movements, nonparetic leg influences on paretic leg coordination were similar and not markedly different from interlimb influences in controls. In bilateral pedaling, however, interlimb influences differed from controls such that paretic leg coordination deficits were exacerbated. During pedaling movements, the suppression of interlimb influences similar to those observed in isometric and discrete movement may occur in controls but may be disrupted in hemiparesis. We suggest that the coupling of pattern generation between the two legs may result in greater, albeit more impaired, paretic leg motor output during bilateral pedaling than during unilateral pedaling.

Microarray analysis of RpoS-mediated gene expression in Escherichia coli K-12.

The alternative sigma factor RpoS controls the expression of many stationary-phase genes in Escherichia coli and other bacteria. Though the RpoS regulon is a large, conserved system that is critical for adaptation to nutrient deprivation and other stresses, it remains incompletely characterized. In this study, we have used oligonucleotide arrays to delineate the transcriptome that is controlled by RpoS during entry into stationary phase of cultures growing in rich medium. The expression of known RpoS-dependent genes was confirmed to be regulated by RpoS, thus validating the use of microarrays for expression analysis. The total number of positively regulated stationary-phase genes was found to be greater than 100. More than 45 new genes were identified as positively controlled by RpoS. Surprisingly, a similar number of genes were found to be negatively regulated by RpoS, and these included almost all genes required for flagellum biosynthesis, genes encoding enzymes of the TCA cycle, and a physically contiguous group of genes located in the Rac prophage region. Negative regulation by RpoS is thus much more extensive than has previously been recognized, and is likely to be an important contributing factor to the competitive growth advantage of rpoS mutants reported in previous studies.

Interindividual variability in acetaminophen glucuronidation by human liver microsomes: identification of relevant acetaminophen UDP-glucuronosyltransferase isoforms.

Interindividual variability in acetaminophen (APAP) glucuronidation may contribute to differences in susceptibility to APAP intoxication in humans. The purpose of this study was to identify the relevant UDP-glucuronosyltransferase (UGT) isoforms mediating APAP-UGT activity in human liver microsomes (HLMs). APAP-UGT activities and enzyme kinetics were determined using HLMs from 56 donors and nine recombinant human UGTs. Activities mediated by UGT1A1, UGT1A4, UGT1A9, and UGT2B7, and relative UGT1A6 protein content were quantified using 20 livers. More than 15-fold variation in liver microsomal APAP-UGT activities was observed with a distribution skewed toward lower activities. Although most UGTs could glucuronidate APAP, UGT1A1, UGT1A6, and UGT1A9 were most active. UGT1A6 was a relatively high-affinity (K(m) = 2.2 mM), low-capacity enzyme; UGT1A1 was intermediate in affinity (K(m) = 9.4 mM) and capacity; and UGT1A9 was a low-affinity (K(m) = 21 mM), high-capacity enzyme. K(m) values were similar to UGT1A1 in high- and intermediate-activity HLMs (6-10 mM) and UGT1A9 in low-activity HLMs (10-55 mM). APAP-UGT activities correlated best with propofol-UGT (r = 0.85; UGT1A9) and bilirubin-UGT (r = 0.66; UGT1A1) activities, but poorly with UGT1A6 protein (r = 0.30). A kinetic model was constructed from these data that identified UGT1A9 as the predominant APAP-UGT (>55% total activity) in HLMs over a clinically relevant APAP concentration range (50 microM-5 mM). UGT1A1 was also predicted to contribute substantially at toxic concentrations (>1 mM; >28% activity), whereas UGT1A6 was most active at relatively low concentrations (<50 microM; >29% activity).

Persistence of depressive symptoms in adolescents.

To examine factors related to the persistence of depressive symptoms, we used a longitudinal follow-up survey of 1,176 adolescents aged 12 to 18 in the United States who reported notable depressive symptoms at baseline. Adolescents were interviewed by telephone at baseline in 1989 and at follow-up in 1993. The outcome of interest was a self-report measure of depressive symptoms experienced within the past 12 months at follow-up. Overall, 38.5% of adolescents reported persistent depressive symptoms. Marked gender differences were found, with 44.5% of girls reporting notable depressive symptoms at follow-up compared with 28.2% for boys. Moreover, current established smokers or experimenters were significantly more likely to report notable depressive symptoms compared with never smokers (42.2%, 41.4% and 33.6%, respectively). Significant multivariate predictors of notable depressive symptoms at follow-up were female gender, change in sleep problems from 1989 to 1993, change in cigarette smoking status from 1989 to 1993, engaging in physical fights, and lack of participation in sports. Many adolescents report continued depressive symptoms over a period spanning four years. Several predictors of persistent depression were identified that could be important components of interventions targeting depressed adolescents.

Behavioral treatment for smokers with a history of alcoholism: predictors of successful outcome.

This study examined baseline predictors associated with smoking abstinence among 205 smokers (113 men, 92 women) with a past history of alcoholism. Their mean age was 41.8 years, and 93% were Caucasian. Participants were randomly assigned to standard treatment (ST), behavioral counseling plus exercise (BEX), or behavioral counseling plus nicotine gum (BNIC). Factors multivariately associated with point-prevalence smoking abstinence at posttreatment (1 week after target quit date) were a longer duration of prior smoking abstinence and an interaction between treatment group and having an active 12-step sponsor. ST was more effective for those with an active sponsor, whereas both BEX and BNIC were more effective for those without an active sponsor. At 1-year follow-up, independent predictors of point-prevalence smoking abstinence were a lower Fagerström Tolerance Questionnaire score (K. O. Fagerström, 1978) and fewer years of smoking.

A community-wide smoking cessation program: Quit and Win 1998 in Olmsted county.

BACKGROUND: Quit and Win is a community-wide stop smoking contest to help cigarette smokers stop smoking and educate the general public concerning smoking hazards. METHODS: All community residents, 15 years of age or older, were eligible to participate in either the stop smoking contest or the supporter contest. A random telephone survey to local households was conducted before and after the Quit and Win contest to assess the level of knowledge and attitude changes about smoking. RESULTS: Of the 304 smokers enrolled in the contest, 42% self-reported continuous tobacco abstinence for the 4-week contest period and 11% were abstinent at 1 year postcontest. Significant predictors for tobacco abstinence during the contest were formal education beyond high school, absence of other smokers in the household, having a support person enrolled in the support person contest, and the type of relationship that the support person had with their smoker. Survey results showed that this contest changed some local attitudes and increased general knowledge of smoking hazards. CONCLUSIONS: Community-wide stop smoking contests can be used to engage smokers and their support in the community and can be successful in reducing tobacco use.

Tobacco use outcomes of adolescents treated clinically for nicotine dependence.

OBJECTIVE: To evaluate the tobacco use outcomes and baseline characteristics of adolescents treated for nicotine dependence. DESIGN: Retrospective cohort study. SETTING: Mayo Clinic Nicotine Dependence Center, Rochester, Minn. PATIENTS: Ninety-six adolescents (60 boys, 36 girls) receiving clinical services for treatment of nicotine dependence between January 1, 1988, and November 30, 1997. Their mean age was 15.6 years (range, 11-17 years), and 91.7% were white. INTERVENTION: The Nicotine Dependence Center intervention involves a 45-minute consultation with a nicotine dependence counselor. A treatment plan individualized to the patient's needs is then developed. Telephone follow-up is conducted at 6 and 12 months. As part of this study, a long-term follow-up was conducted by telephone at a mean of 5.3 years (range, 1.6-10.6 years) following the intervention. MAIN OUTCOME MEASURES: Self-reported 7-day point-prevalence abstinence from tobacco at 6 and 12 months, and 30-day point-prevalence tobacco abstinence at the long-term follow-up. RESULTS: The tobacco abstinence rates were 17.7% (17/96 patients) at 6 months, 7.3% (7/96 patients) at 12 months, and 11.5% (11/96 patients) at the long-term follow-up. A high proportion of the sample had smoking-related medical morbidity and psychiatric diagnoses documented in the medical record prior to or at the time of the intervention. CONCLUSIONS: Adolescents utilize the medical community to seek treatment for nicotine dependence. The 6-month tobacco abstinence rate is higher than the estimates of the natural history of smoking cessation in adolescents. Medical and psychiatric diagnoses are common in this population.

Alternative splicing determines the function of CYP4F3 by switching substrate specificity.

Diversity of cytochrome P450 function is determined by the expression of multiple genes, many of which have a high degree of identity. We report that the use of alternate exons, each coding for 48 amino acids, generates isoforms of human CYP4F3 that differ in substrate specificity, tissue distribution, and biological function. Both isoforms contain a total of 520 amino acids. CYP4F3A, which incorporates exon 4, inactivates LTB4 by omega-hydroxylation (Km = 0.68 microm) but has low activity for arachidonic acid (Km = 185 microm); it is the only CYP4F isoform expressed in myeloid cells in peripheral blood and bone marrow. CYP4F3B incorporates exon 3 and is selectively expressed in liver and kidney; it is also the predominant CYP4F isoform in trachea and tissues of the gastrointestinal tract. CYP4F3B has a 30-fold higher Km for LTB4 compared with CYP4F3A, but it utilizes arachidonic acid as a substrate for omega-hydroxylation (Km = 22 microm) and generates 20-HETE, an activator of protein kinase C and Ca2+/calmodulin-dependent kinase II. Homology modeling demonstrates that the alternative exon has a position in the molecule which could enable it to contribute to substrate interactions. The results establish that tissue-specific alternative splicing of pre-mRNA can be used as a mechanism for changing substrate specificity and increasing the functional diversity of cytochrome P450 genes.

Relationship of mood disturbance to cigarette smoking status among 252 patients with a current mood disorder.

BACKGROUND: The relationship between cigarette smoking and mood has received increasing attention. This retrospective study evaluated the relationship between mood disturbance and cigarette smoking status among patients with a current mood disorder. The association between level of nicotine dependence and severity of mood disturbance was also evaluated among current smokers. METHOD: Retrospective data for 252 patients (63.5% male, 85.0% white) admitted for treatment of a mood disorder at the San Diego Veteran Affairs Mental Health Clinical Research Center between November 1988 and June 1997 were studied. All current cigarette smokers at admission (N = 126) were matched with nonsmokers (N = 126) on the primary DSM-IV Axis I mood disorder diagnosis, admission status (inpatient or outpatient), gender, age (+/- 5 years), and ethnicity. The Hamilton Rating Scale for Depression (HAM-D), the Beck Depression Inventory, and the Profile of Mood States (POMS) were administered to patients on admission. Conditional logistic regression analysis for matched sets with a backward elimination was used to identify factors independently predictive of current smoking status. RESULTS: A greater number of cups of coffee consumed per day (p = .002), a history of alcoholism (p = .004), and higher POMS fatigue subscale scores (p = .007) were predictive of current smoking status. Among current smokers, the HAM-D terminal insomnia item was positively associated with mean number of cigarettes smoked per day (p = .012). CONCLUSION: Cigarette smoking should be addressed in the treatment of patients with a current mood disorder. Smokers experience greater levels of fatigue than nonsmokers. In addition, higher cigarette consumption levels are associated with mild-to-severe symptoms of terminal insomnia.

Adaptations in maximal motor unit discharge rate to strength training in young and older adults.

Six young (mean = 23 years) and 6 older (mean = 76 years) adults participated in isometric resistance training 5 days/week for 6 weeks. The task involved isometric fifth finger abduction. Maximal motor unit discharge rates (MUDRs) were obtained from the abductor digiti minimi of each hand at 0, 2, 14, and 42 days of training using a quadrifilar needle electrode and automatic spike recognition software. In agreement with previous findings, maximal MUDR at baseline was significantly lower in older adults (P < 0.001), averaging 51.5 (+/-17.13) HZ in young and 43.3 (+/-14.88) HZ in older adults. In response to resistance training, maximal voluntary force increased 25% in young and 33% in older subjects (P < 0.001). Maximal MUDR increased significantly (11% young, 23% older) on day 2 [F(3,36) = 2.58, P < 0.05], but in older subjects returned to baseline levels thereafter. These adaptations in abductor digiti minimi MUDR suggest a two-part response to strengthening fifth finger abduction: early disinhibition followed by altered MU activation.

The effects of transdermal nicotine therapy for smoking cessation on depressive symptoms in patients with major depression.

This study examines the effects of transdermal nicotine patches for smoking cessation on depressive and withdrawal symptoms among 38 non-medicated subjects with Major Depressive Disorder. The study was conducted over a 29-day period, which included a 7 day baseline phase, a 14 day treatment phase, and an 8 day placebo phase. During the treatment phase subjects received either active nicotine patches (N = 18) or placebo patches (N = 20) that were administered in a randomized, double-blind fashion. The target quit date (TQD) was day 8. Significantly, more subjects in the placebo group than in the nicotine group resumed smoking following the TQD (50% vs. 22%). There was little evidence for effects of active nicotine patches on measures of mood (HRSD, BDI, POMS) or withdrawal symptoms among subjects that remained abstinent throughout the study (N = 24). Those who resumed smoking had more severe withdrawal symptoms than those who remained abstinent. One patient in the placebo group (n = 20) became more depressed after 2 weeks of abstinence. None of the patients in the nicotine group (n = 18) became more depressed.