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The current study examined the relationship between scores on social complexity and psychological health. A sample of 202 college students yielded positive correlations for propensity to join and maintain memberships in diverse groups with psychological health, thereby replicating past research.
PURPOSE: Mice favoring Th1 (C57BL/6, C57BL/10, and B10.D2/nSn) versus Th2 (BALB/c, BALB/cBy, BALB.B, and BALB.K) response development were evaluated for their response to infection with Pseudomonas aeruginosa. This study addresses the question of whether Th1 versus Th2 response propensity affects the pathogenesis of bacterial keratitis in mice. METHODS: Ocular disease was determined by mean clinical score, slit lamp, plate counts, and histopathology, and antigen-specific cellular responses were assessed by immunostaining and measurement of delayed type hypersensitivity (DTH). RESULTS: Strains of mice favoring Th1 (B6, BL10, and B10.D2) versus Th2 (BALB/c, BALB/cBy, BALB.B, and BALB.K) responsiveness were infected with P. aeruginosa. Mice favoring Th1 response development exhibited a similar course of disease and the infected eyes of all mice perforated by 7 days postinfection (p.i.). Strains (BALB/c, BALB/cBy, BALB.B, and BALB.K) favoring Th2 response development exhibited a milder course of disease, and none of the infected corneas perforated at 7 days p.i. In a Th1-responsive strain (B10.D2), positive immunostaining for CD4+ and CD8+ T cells was observed in the cornea by 3 days p.i. and by 5 days p.i., respectively, some cells stained positively for IL2-R, indicating that the cells were activated. In contrast, in a Th2 responder strain (BALB/c), there was no detectable positive immunostaining in cornea for any of the T-cell markers tested and DTH was significantly elevated in B10.D2 versus BALB/c mice. CONCLUSIONS: These studies are the first to provide evidence that in P. aeruginosa ocular infection, mouse strains favoring development of a Th1-type response are susceptible (cornea perforates), whereas strains favoring Th2 response development are resistant (no corneal perforation).
The prognosis of canine soft-tissue sarcomas (STS) has traditionally been based on histologic grading. We have recently demonstrated the prognostic value of cellular proliferation markers in canine STS. Another method of predicting the behavior of neoplasms is intratumoral microvessel density (IMD), which is a measure of tumor angiogenesis. The prognostic significance of IMD has been documented in many human neoplasms and in a limited number of canine and feline neoplasms. To evaluate the prognostic value of IMD in canine STS, we studied 57 STS and compared IMD with histologic features, histologic grade, cellular proliferation, metastatic propensity, and survival. Using immunohistochemistry, the STS were labeled with anti-factor VIII-related antigen (FVIII-RA) and anti-CD31 antibodies to determine 3 IMD parameters: mean microvessel density, high microvessel density, and microvessel area. Using FVIII-RA and CD31, increasing IMD was statistically associated with increasing histologic grade, necrosis scores, and mitotic scores. Higher FVIII-RA IMD values were significantly associated with higher median argyrophilic nucleolar organizing region (AgNOR) values (as previously investigated) and increased metastatic propensity. Fibrosarcomas appear to be the least vascularized of STS. There is no correlation between IMD and survival. Our results indicate that IMD is of prognostic value for histologic grade, histologic features, cellular proliferation (based on AgNOR), and metastatic propensity of canine STS, specifically when using FVIII-RA as the endothelial marker. Assessing histologic grading, cellular proliferation, and IMD of canine STS at the time of diagnosis could therefore provide better prognostic information for the veterinary clinician.
Most polysomnograms are performed because sleep-disordered breathing (SDB) is suspected, but periodic leg movements during sleep (PLMS) are frequent incidental findings, and their significance is not well understood. In a clinical series of 1,124 adult patients with suspected or confirmed SDB, we tested for an association between the rate of periodic leg movements and one important outcome, the severity of daytime sleepiness. Objective sleepiness was assessed by the Multiple Sleep Latency Test in all subjects, problem sleepiness by self-rating in 873, and subjective sleep propensity by the Epworth Sleepiness Scale in 201. Increased leg movements were associated with decreased objective sleepiness (p = 0.03) but explained less than 1% of the variance. When nocturnal arousals were scored (n = 321 subjects), rates of leg movements associated with arousals predicted less objective sleepiness (p = 0.008); rates of leg movements without arousals predicted nothing. The rates of leg movements showed no association with subjective problem sleepiness or sleep propensity. We conclude that incidental periodic leg movements during sleep are not associated with excessive daytime sleepiness, and therefore appear unlikely to contribute to this problem. Increased sleepiness may reduce the likelihood of arousal with each leg movement.
We have developed the following web servers for protein structural modeling and analysis at http://theory.med.buffalo.edu: THUMBUP, UMDHMM(TMHP) and TUPS, predictors of transmembrane helical protein topology based on a mean-burial-propensity scale of amino acid residues (THUMBUP), hidden Markov model (UMDHMM(TMHP)) and their combinations (TUPS); SPARKS 2.0 and SP3, two profile-profile alignment methods, that match input query sequence(s) to structural templates by integrating sequence profile with knowledge-based structural score (SPARKS 2.0) and structure-derived profile (SP3); DFIRE, a knowledge-based potential for scoring free energy of monomers (DMONOMER), loop conformations (DLOOP), mutant stability (DMUTANT) and binding affinity of protein-protein/peptide/DNA complexes (DCOMPLEX & DDNA); TCD, a program for protein-folding rate and transition-state analysis of small globular proteins; and DOGMA, a web-server that allows comparative analysis of domain combinations between plant and other 55 organisms. These servers provide tools for prediction and/or analysis of proteins on the secondary structure, tertiary structure and interaction levels, respectively.
67Gallium-citrate scans were performed on 45 patients with acute lymphoblastic leukemia (ALL) at the time of diagnosis. The extent of uptake and distribution of gallium were compared to known prognostic indicators of age, initial white count, and bone marrow lymphoblast immune markers (T, B, and null cell). Selective increased uptake was noted in bone, kidney, liver/spleen, lymph nodes, or other sites in 29 patients, and 16 patients had "normal" scans. A scoring system giving one point for selective uptake in each organ system was used. Patients were grouped according to scores of zero, 1--2, and 3 or greater. There was no significant correlation found between total gallium scores and any of the three prognostic indicators. There was also no significant correlation when prognostic factors were compared to uptake in the individual organ systems except that T cell disease was associated with a significantly greater propensity for lymph node uptake. There was a suggestion that children with "normal" gallium scans may have a better long-term prognosis, since 6 of 7 nonrelapsers observed for longer than 18 months had scores of zero at diagnosis compared to 4 of 6 early deaths with scores greater than zero. This study indicates that the 67Ga scan does not significantly correlate with known prognostic indicators, with the possible exception of lymph node uptake in T cell disease, and its value as an independent indicator of long-term survival will require longer follow-up.
Human Rad51 and Rad52 are implicated in DNA repair during replication. Here we show, by pull-down assays, that purified hRad51 and hRad52 interact with each other as well as with Mini chromosome maintenance (MCM) proteins in HeLa cell extracts. Furthermore, immunoprecipitation experiments corroborate the same where hRad51 and hRad52 proteins not only cross-talk with each other but also pull down MCM3 and MCM2/3 proteins, respectively. The interaction scoring assays, performed reciprocally, demonstrate the same specificity, based on which, we speculate that MCM complex exhibits strong propensity to get physically recruited to the sites where hRad51 and hRad52-mediated homologously aligned ends need to be replicationally repaired.
The identification and annotation of protein domains provides a critical step in the accurate determination of molecular function. Both computational and experimental methods of protein structure determination may be deterred by large multi-domain proteins or flexible linker regions. Knowledge of domains and their boundaries may reduce the experimental cost of protein structure determination by allowing researchers to work on a set of smaller and possibly more successful alternatives. Current domain prediction methods often rely on sequence similarity to conserved domains and as such are poorly suited to detect domain structure in poorly conserved or orphan proteins. We present here a simple computational method to identify protein domain linkers and their boundaries from sequence information alone. Our domain predictor, Armadillo (http://armadillo.blueprint.org), uses any amino acid index to convert a protein sequence to a smoothed numeric profile from which domains and domain boundaries may be predicted. We derived an amino acid index called the domain linker propensity index (DLI) from the amino acid composition of domain linkers using a non-redundant structure dataset. The index indicates that Pro and Gly show a propensity for linker residues while small hydrophobic residues do not. Armadillo predicts domain linker boundaries from Z-score distributions and obtains 35% sensitivity with DLI in a two-domain, single-linker dataset (within +/-20 residues from linker). The combination of DLI and an entropy-based amino acid index increases the overall Armadillo sensitivity to 56% for two domain proteins. Moreover, Armadillo achieves 37% sensitivity for multi-domain proteins, surpassing most other prediction methods. Armadillo provides a simple, but effective method by which prediction of domain boundaries can be obtained with reasonable sensitivity. Armadillo should prove to be a valuable tool for rapidly delineating protein domains in poorly conserved proteins or those with no sequence neighbors. As a first-line predictor, domain meta-predictors could yield improved results with Armadillo predictions.
A study on the epidemiology and seasonal dynamics of gastrointestinal nematode infections of sheep was carried out in a semi-arid region of eastern Ethiopia for 2.5 years (May 2003 to September 2005). The experimental flock comprised a total of 60 Black Head Ogaden sheep, consisting of four equal groups of young male and female and old male and female sheep. These grazed on communal pastures together with a larger university flock, as well as with animals owned by neighbouring small-holder farmers. A new experimental flock was established each year of the study. Parasitological data (EPG, faecal culture L3, PCV and FAMACHA estimates) and animal performance (weight change) were recorded each month on all experimental animals. In addition, four tracer lambs were assigned each month to the flock to determine the seasonal patterns of infective larvae acquired from pasture. Results showed distinct seasonal patterns associated with the bi-modal annual rainfall. High levels of infection occurred during the short and long rain seasons with peaks occurring in May and September of each year. Haemonchus contortus was the most prevalent parasite, followed by Trichostrongylus spp., with a number of other nematode species being occasionally recorded. H. contortus showed and increased propensity to undergo arrested development during the dry seasons. Correlations between EPG and PCV, EPG and FAMACHA eye scores, and PCV and FAMACHA eye scores were all highly significant (P<0.001). However, there was no significant association between the EPG and LW of the study animals during each study year. This information will provide a basis for developing epidemiologically based control strategies for gastrointestinal nematode parasites that are appropriate for flocks owned by small-holder farmers of semi-arid areas of eastern Ethiopia.
ArchPRED server (http://www.fiserlab.org/servers/archpred) implements a novel fragment-search based method for predicting loop conformations. The inputs to the server are the atomic coordinates of the query protein and the position of the loop. The algorithm selects candidate loop fragments from a regularly updated loop library (Search Space) by matching the length, the types of bracing secondary structures of the query and by satisfying the geometrical restraints imposed by the stem residues. Subsequently, candidate loops are inserted in the query protein framework where their side chains are rebuilt and their fit is assessed by the root mean square deviation (r.m.s.d.) of stem regions and by the number of rigid body clashes with the environment. In the final step remaining candidate loops are ranked by a Z-score that combines information on sequence similarity and fit of predicted and observed [/psi] main chain dihedral angle propensities. The final loop conformation is built in the protein structure and annealed in the environment using conjugate gradient minimization. The prediction method was benchmarked on artificially prepared search datasets where all trivial sequence similarities on the SCOP superfamily level were removed. Under these conditions it was possible to predict loops of length 4, 8 and 12 with coverage of 98, 78 and 28% with at least of 0.22, 1.38 and 2.47 A of r.m.s.d. accuracy, respectively. In a head to head comparison on loops extracted from freshly deposited new protein folds the current method outperformed in a approximately 5:1 ratio an earlier developed database search method.
This study evaluated the effects of different amounts of sleep and SWS restriction on the ensuing day-time sleepiness. Six healthy selected males, after one adaptation night and an initial 8-hr baseline night, were allowed to sleep 5, 4, 3, 2, and 1 hr with a 1-week interval between conditions. The following day, 4 sleep onset MSLT trials and 2 Wilkinson Auditory Vigilance Task (WAVT) were administered. Before each MSLT, self evaluations of sleepiness and activation on a visual analogue scale (ADAS) were assessed. Each restriction night was followed by an 8-hr recovery night, and a final 8-hr baseline night was recorded. The day after each night the same diurnal tests were repeated. Results indicated a linear increase in the propensity to sleep (MSLT) and of subjective sleepiness as a function of the increase in sleep restrictions. Performance scores (WAVT) showed that vigilance is partially affected by sleep restrictions. For each measure, regression analyses showed that the effect of sleep reduction is better predicted by the total duration of sleep than by the amount of SWS. Correlations between measures were negligible with the exception of those between performance and subjective sleepiness measures.
BACKGROUND: Reports of major and minor sequelae following lidocaine spinal anesthesia have generated interest in an alternative short-acting intrathecal agent. Of the available anesthetics suitable for short-duration spinal anesthesia, prilocaine is perhaps the most promising agent. However, data comparing the neurotoxicity of these agents are lacking. Accordingly, the present experiments investigate whether prilocaine and lidocaine differ with respect to sensory impairment and histologic damage when administered intrathecally in the rat. METHODS: Ninety rats were divided into three groups to receive an intrathecal infusion of 2.5% prilocaine in saline, 2.5% lidocaine in saline, or normal saline. The animals were assessed for persistent sensory impairment 4 days after anesthetic administration using the tail-flick test. Three days later, the animals were killed, and specimens of the spinal cord and nerve roots were obtained for histopathologic examination. RESULTS: Prilocaine and lidocaine produced equivalent elevations in tail-flick latency that differed significantly from saline. Histologic injury scores with prilocaine were greater than with lidocaine, but this difference did not reach statistical significance. CONCLUSIONS: The propensity for persistent functional impairment or morphologic damage with intrathecal prilocaine is at least as great as with lidocaine. Although the substitution of prilocaine for lidocaine may reduce the incidence of transient neurologic symptoms, it is unlikely to reduce the risk of actual neural injury. This discrepancy may indicate that transient neurologic symptoms and neurologic deficits after spinal anesthesia are not mediated by the same mechanism.
Data from 27 girls of 10 to 12 years were obtained on the Fear Survey Schedule for Children--Revised and from their parents on the Fear Survey Schedule for Adults-III and the California F Scale. Analyses indicated fathers' authoritarianism scores and mothers' fear scores have independent associations with children's fears and suggested greater behavioural overcontrol by fathers and the greater propensity of mothers to communicate threatening information.
BACKGROUND: Only little is known about factors that influence the smokers' propensity to start smoking cessation therapy and stay within such programs. METHODS: One hundred fifteen subjects that were current smokers and presented at the angiologic outpatient unit were enrolled in a prospective cohort study. All patients were invited to take part in a smoking cessation program. Patients' history, noninvasive vascular, cardiac, and pulmonary parameters, state of atherosclerotic disease (SMART-score), smoking history, and Fagerström index were obtained and the carbon monoxide breathing test was performed. RESULTS: Lower age and heavy smoking were associated with less propensity to start smoking cessation therapy. The degree of atherosclerosis significantly predicted short-term commitment to smoking cessation therapy (relative risk for discontinuation: 0.82; 95% CI: 0.70-0.96). Single factors predictive for staying within the therapy were peripheral arterial occlusive disease and hyperlipidemia, while neither prior myocardial infarction nor pulmonary function was associated with compliance. Fifty-four percent of patients that completed 3 months of therapy quit smoking. CONCLUSIONS: Counseling in smokers with preexistent or newly diagnosed atherosclerotic diseases or risk factors should include their specific vascular condition and information on positive consequences on the progress of these conditions. Counseling for initiation of smoking cessation therapy should apply different strategies as used in the maintenance phase of therapy.
BACKGROUND: Risedronate increases bone mineral density in elderly women, but whether it prevents hip fracture is not known. METHODS: We studied 5445 women 70 to 79 years old who had osteoporosis (indicated by a T score for bone mineral density at the femoral neck that was more than 4 SD below the mean peak value in young adults [-4] or lower than -3 plus a nonskeletal risk factor for hip fracture, such as poor gait or a propensity to fall) and 3886 women at least 80 years old who had at least one nonskeletal risk factor for hip fracture or low bone mineral density at the femoral neck (T score, lower than -4 or lower than -3 plus a hip-axis length of 11.1 cm or greater). The women were randomly assigned to receive treatment with oral risedronate (2.5 or 5.0 mg daily) or placebo for three years. The primary end point was the occurrence of hip fracture. RESULTS: Overall, the incidence of hip fracture among all the women assigned to risedronate was 2.8 percent, as compared with 3.9 percent among those assigned to placebo (relative risk, 0.7; 95 percent confidence interval, 0.6 to 0.9; P=0.02). In the group of women with osteoporosis (those 70 to 79 years old), the incidence of hip fracture among those assigned to risedronate was 1.9 percent, as compared with 3.2 percent among those assigned to placebo (relative risk, 0.6; 95 percent confidence interval, 0.4 to 0.9; P=0.009). In the group of women selected primarily on the basis of nonskeletal risk factors (those at least 80 years of age), the incidence of hip fracture was 4.2 percent among those assigned to risedronate and 5.1 percent among those assigned to placebo (P=0.35). CONCLUSIONS: Risedronate significantly reduces the risk of hip fracture among elderly women with confirmed osteoporosis but not among elderly women selected primarily on the basis of risk factors other than low bone mineral density.
The frequencies of occurrence of atom arrangements in high-resolution protein structures provide some of the most accurate quantitative measures of interaction energies in proteins. In this report we extend our development of a consistent set of statistical potentials for quantifying local interactions between side-chains and the polypeptide backbone, as well as nearby side-chains. Starting with phi/psi/chi1 propensities that select for optimal interactions of the 20 amino acid side-chains with the 2 flanking peptide bonds, the following 3 new terms are added: (1) a distance-dependent interaction between the side-chain at i and the carbonyl oxygens and amide protons of the peptide units at i +/- 2, i +/- 3, and i +/- 4; (2) a distance-dependent interaction between the side-chain at position i and side-chains at positions i + 1 through i + 4; and (3) an orientation-dependent interaction between the side-chain at position i and side-chains at i + 1 through i + 4. The relative strengths of these 4 pseudo free energy terms are estimated by the average information content of each scoring matrix and by assessing their performance in a simple fragment threading test. They vary from -0.4 - -0.5 kcal/mole per residue for phi/psi/chi1 propensities to a range of -0.15 - -0.6 kcal/mole per residue for each of the other 3 terms. The combined energy function, containing no interactions between atoms more than 4 residues apart, identifies the correct structural fragment for randomly selected 15 mers over 40% of the time, after searching through 232,000 alternative conformations. For 14 out of 20 sets of all-atom Rosetta decoys analyzed, the native structure has a combined score lower than any of the 1700-1900 decoy conformations. The ability of this energy function to detect energetically important details of local structure is demonstrated by its power to distinguish high-resolution crystal structures from NMR solution structures.
The aim of this population based case-control study was to examine the association between risk-taking behaviour, motor coordination and upper limb fractures in children aged 9-16 years. A total of 321 fracture cases and 321 randomly selected individually matched controls were studied. The number for different types of upper limb fractures was 91 for hand, 190 for wrist and forearm and 40 for upper arm. Risk-taking behaviour was determined by a 5-item interview-administered questionnaire. Motor coordination was assessed by the 8-point movement ABC that tests manual dexterity, ball skills as well as static and dynamic balance. Bone mass was assessed by dual energy X-ray absorptiometry (DXA) and metacarpal morphometry. In general, there was heterogeneity by fracture site with regard to associations. Risk-taking behaviour was associated with hand fracture risk but not other fracture sites for downhill cycling behaviour (OR: 2.0/category, 95% CI: 1.1-3.7), dare behaviour (OR: 3.3/category, 95% CI: 1.1-10.0) and total risk-taking score (OR: 2.6/category, 95% CI: 1.3-5.7). Conversely, coordination measures were associated with wrist and forearm fractures only: cutting/threading (OR: 1.2/unit, 95% CI: 1.0-1.4); flower trail (OR: 1.2/unit, 95% CI: 1.0-1.4) and dynamic balance score (OR: 1.1/unit, 95% CI: 1.0-1.2). Backward stepwise analysis selected total risk taking score for hand fracture, and dynamic balance score for wrist and forearm fracture. None of the risk-taking or coordination scores were associated with upper arm fractures. These associations were unchanged following adjustment for bone mass. In conclusion, the propensity to take risks is most strongly associated with hand fracture risk while dynamic balance is most strongly associated with wrist and forearm fracture risk in children. These results inform the development of fracture prevention strategies in children.
The paper focuses on studying the cognitive determinants of obesity within the framework of the cognitive orientation (CO) theory. This theory assumes that cognitive contents and processes guide behavior, and specifies procedures for predicting and changing behaviors. The subjects were 64 obese and 64 nonobese women matched in age, height and other demographic variables. They were administered the MMPI and a CO questionnaire of obesity which assessed beliefs of four types (about goals, rules and norms, self and general beliefs) concerning 20 themes found to represent the meanings of food, eating and obesity. The results showed that the groups did not differ and had no elevated scores on any of the MMPI scales. The obese had higher scores than the controls on each of the belief types, an overall belief index, 19 themes and a conflict propensity measure. A discriminant analysis showed 88.3 percent correct identifications on the basis of the beliefs. Discussion focused on the role of conflicts and the different themes in obesity and on outlining the elements of a CO model of obesity with therapeutic implications.