Morphological and molecular characterization of Langdonia walkerae sp. nov. infecting Aristida stricta and A. beyrichiana in longleaf pine-grassland ecosystems in the southeastern USA.

A smut fungus that hinders wiregrass restoration efforts in longleaf pine-grassland ecosystems was collected from Aristida stricta and A. beyrichiana (Poaceae) in three states in the southeastern USA. Morphological and phylogenetic characteristics of this fungus were examined. These data show that the specimens from both plant species were infected by the same fungus and represent a new species of Langdonia. The new species differs morphologically from other species of Langdonia by teliospores being solitary and not compacted into spore balls. Spore wall ornamentation and teliospore size also differ from other Langdonia species. Phylogenetic analyses of DNA sequences of the ITS, LSU, and EF-1α supported separation of the species from A. stricta and A. beyrichiana from other Langdonia species. Based on these results, a new species, Langdonia walkerae, is proposed.

Traumatic brain injury in pedestrian-vehicle collisions: Convexity and suitability of some functionals used as injury metrics.

BACKGROUND AND OBJECTIVE: Abrupt accelerations or decelerations can cause large strain in brain tissues and, consequently, different forms of Traumatic Brain Injury (TBI). In order to predict the effect of the accelerations on the soft tissues of the brain, many different injury metrics have been proposed (typically, an injury metric is a real valued functional of the accelerations). The objective of this article is to make a formal and empirical comparison, in order to identify general criteria for reasonable injury metrics, and propose a general guideline to avoid ill-proposed injury metrics. METHODS: A medium-sized sample of vehicle-pedestrian collisions, from Post Mortem Human Subject (PMHS) tests, is analyzed. A statistical study has been conducted in order to determine the discriminant power of the usual metrics. We use Principal Component Analysis to reduce dimensionality and to check consistency among the different metrics. In addition, this article compares the mathematical properties of some of these functionals, trying to identify the desirable properties that any of those functionals needs to fulfill in order to be useful for optimization. RESULTS: We have found a pair-wise consistency of all the currently used metrics (any two injury metrics are always positively related). In addition, we observed that two independent principal factors explain about 72.5% of the observed variance among all collision tests. This is remarkable because it indicates that despite high number of different injury metrics, a reduced number of variables can explain the results of all these metrics. With regard to the formal properties, we found that essentially all injury mechanisms can be accounted by means of scalable, differentiable and convex functionals (we propose to call minimization suitable injury metric any metric having these three formal properties). In addition three useful functionals, usable as injury metrics, are identified on the basis of the empirical comparisons. CONCLUSIONS: The commonly used metrics are highly consistent, but also highly redundant. Formal minimal conditions of a reasonable injury metric has been identified. Future proposals of injury metrics can benefit from the results of this study.

Human surrogates for injury biomechanics research.

This article reviews the attributes of the human surrogates most commonly used in injury biomechanics research. In particular, the merits of human cadavers, human volunteers, animals, dummies, and computational models are assessed relative to their ability to characterize the living human response and injury in an impact environment. Although data obtained from these surrogates have enabled biomechanical engineers and designers to develop effective injury countermeasures for occupants and pedestrians involved in crashes, the magnitude of the traffic safety problem necessitates expanded efforts in research and development. This article makes the case that while there are limitations and challenges associated with any particular surrogate, each provides a critical and necessary component in the continued quest to reduce crash-related injuries and fatalities.

White matter density is increased in patients with hypothalamic hamartoma and multiple seizure types.

Many patients with hypothalamic hamartomas present in infancy with gelastic seizures of subcortical origin, but later develop additional seizure types, including complex partial, tonic, and generalized tonic-clonic seizures. The basic cellular mechanisms responsible for this evolution in seizure types are unknown. Using voxel-based morphometry of T1 weighted MRI scans we compared eight patients with only gelastic seizures with 16 age-matched patients with multiple seizure types and found significantly greater white matter density in the temporal lobes and cerebellum in those with multiple seizure types. This suggests that increased white matter density, perhaps resulting from maturational changes and resulting in increased brain connectivity, is associated with a higher likelihood of cortical involvement in epilepsy resulting from hypothalamic hamartoma.

Endoscopic resection of hypothalamic hamartomas for refractory symptomatic epilepsy.

BACKGROUND: Hypothalamic hamartomas (HHs), rare developmental abnormalities of the inferior hypothalamus, often cause refractory, symptomatic, mixed epilepsy, including gelastic seizures. We present 37 patients with HH who underwent transcortical transventricular endoscopic resection. METHODS: Between October 2003 and April 2005, 42 consecutive patients with refractory epilepsy who underwent endoscopic resection of HH were studied prospectively. The endoscope was held by an articulated pneumatic arm and tracked with a frameless stereotactic neuronavigation system. Data collection and follow-up were performed by personal interview. Five patients were excluded. The remaining 37 patients (22 males, 15 females; median age 11.8 years; range 8 months to 55 years) had frequent and usually multiple types of seizures. RESULTS: Postoperative MRI confirmed 100% resection of the HH from the hypothalamus in 12 patients. At last follow-up (median 21 months; range 13-28 months), 18 (48.6%) patients were seizure free. Seizures were reduced more than 90% in 26 patients (70.3%) and by 50% to 90% in 8 patients (21.6%). Overall, the mean postoperative stay was shorter in the endoscopic patients compared with our previously reported patients who underwent transcallosal resection (mean 4.1 days vs 7.7 days, respectively; p = 0.0006). The main complications were permanent short-term memory loss in 3 patients and small thalamic infarcts in 11 patients (asymptomatic in 9). CONCLUSIONS: Endoscopic resection of hypothalamic hamartoma (HH) is a safe and effective treatment for seizures. Its efficacy seems to be comparable to that of transcallosal resection of HH, but postoperative recovery time is significantly shorter.

Modeling and biochemical analysis of the activity of antibiofilm agent Dispersin B.

Bacteria in a biofilm are enmeshed in a self-synthesized extracellular polysaccharide matrix (PGA), which is a linear polymer of beta(1,6)-linked N-acetylglucosamine (GlcNAc) residues. Dispersin B (DspB), a soluble glycoside hydrolase produced by the periodontal pathogen Actinobacillus actinomycetemcomitans degrades PGA. The enzyme DspB is an alpha/beta TIM-barrel protein and belongs to family 20 glycosyl hydrolases members. The enzyme activity of DspB with regard to its substrate specificity towards beta(1,6)-linked GlcNAc polymers and its endo/exo character was investigated through ligand docking and the hydrolysis of synthetic oligosaccharides. Ligand docking analysis suggested that beta(1,6)-linked GlcNAc oligosaccharide bound to the active site better that beta(1,4)-linked GlcNAc oligosaccharide. Our combined results indicate that DspB is an exo-acting enzyme that hydrolyzes beta(1,6)-linked N-acetylglucosamine oligomers.

Nonlinear viscoelastic behavior of human knee ligaments subjected to complex loading histories.

The nonlinear viscoelastic structural response of the major human knee ligaments when subjected to complex loading histories is investigated, with emphasis on the collateral ligaments. Bone-ligament-bone specimens are tested in knee distraction loading, where the ligaments are in the anatomical position corresponding to a fully extended knee. Temporal nonlinearities for time scales in the range of 1

Hypothalamic hamartomas: Correlation of MR imaging and spectroscopic findings with tumor glial content.

BACKGROUND AND PURPOSE: There is variability in the literature concerning the appearance and histology of hypothalamic hamartomas. This study correlates the MR imaging and proton MR spectroscopic properties of hypothalamic hamartomas with histopathologic findings. METHODS: Studies were performed with 3T and 1.5T scanners. Single voxel hamartoma spectra were acquired by using short-echo-time point-resolved spectroscopy sequences (PRESS). 2D PRESS chemical shift imaging (CSI) spectroscopic sequences were also obtained for comparison of tumor-derived spectra with normal gray matter of the amygdala. Sequences were used to compare choline (Cho), N-acetylaspartate (NAA), and myoinositol (mI) resonances by using a creatine (Cr) reference. Spectral ratios and T2 signal intensity ratios of the hamartomas were then compared with histopathologic findings. RESULTS: Data from single voxel spectroscopic sequences demonstrated a statistically significant decrease in NAA/Cr and an increase in mI/Cr ratios in tumor tissue when compared with values in normal gray matter of the amygdala. In addition, Cho/Cr ratios were also increased when compared with those in normal gray matter controls. Among the 14 hamartomas sampled, a spectrum of increased mI/Cr ratios was seen. Those tumors with markedly elevated mI/Cr demonstrated an increased glial component when compared with the remaining tumors. Increased glial component was also found to have a positive correlation with hyperintensity of lesions on T2-weighted images. CONCLUSION: We have identified a correlation between the glial/neuronal fraction as determined by histopathology and MR spectral and T2 hyperintensity variations among hypothalamic hamartomas.

Costs and quality of life of multiple sclerosis in the United Kingdom.

This cost-of-illness analysis for the United Kingdom is part of a Europe-wide study on the costs of multiple sclerosis (MS). The objective was to analyze the costs and quality of life (utility) related to the level of disease severity. People with MS from a database administered by a UK charity (the MS Trust) were asked to participate in the survey by answering a postal questionnaire. In addition to details on the disease (type of disease, relapses, level of functional disability), the questionnaire asked for information on all resource consumption, medical, non-medical, work absence and informal care as well as utility. The response rate was 19%, and a total of 2048 people were included. The mean age of the cohort was 51 years, and 23% of people were > or =60 years of age. Disease severity was concentrated in people with moderately severe MS (Expanded Disability Status Scale [EDSS] score of 4 to 6.5), with 21, 60 and 19% of people reporting mild, moderate and severe disease, respectively. Costs and utility are highly correlated with disease severity. Mean annual costs for all people in the study increase from approximately pound 12.000 at an EDSS score <4 to almost pound 60.000 at an EDSS score > or =7. In particular, employment rates are reduced from 82% in early disease to 2% at an EDSS score of 8, while the costs of inpatient care, investments, informal care and productivity losses increase by more than tenfold between an EDSS score of 0-1 and a score > or =7. Utility decreases from 0.92 at an EDSS score of 0 to a state worse than death in the most severe state (-0.18 at an EDSS score of 9). Compared to the results in an earlier cost study in the United Kingdom using a comparable methodology, costs have substantially increased, by roughly 40%. Part of the increase is due to a higher use of disease-modifying drugs and, possibly linked with this, a higher use of ambulatory care and services. Another part of the increase is most likely due to an increased age in the current sample, with more patients on early retirement due to MS and more intense use of informal care. However, another reason may lie in the methodology, e.g. different unit costs or differences in the sample distribution, despite a similar mean EDSS score of 5.1.

Pedestrian injuries: viscoelastic properties of human knee ligaments at high loading rates.

OBJECTIVE: Accidents involving pedestrians are very common, and often lead to severe injuries to the lower extremities. In a large portion of pedestrian-automobile collisions, knee ligament injuries are sustained. In this study, the viscoelastic properties of the four major human knee ligaments were investigated at loading rates representative for pedestrian-automobile collisions. METHODS: Bone-ligament-bone specimens were tested in knee distraction loading. The collateral ligaments and the separate functional bundles of the cruciate ligaments were tested in the anatomical position corresponding to a fully extended knee. A series of step-and-hold tests and ramp tests at different rates were conducted to characterize the time-dependent behavior of the knee ligaments for deformation rates associated with the pedestrian impact loading environment. The quasi linear viscoelastic (QLV) theory was used to describe the structural response of the knee ligaments and averaged parameters for this model were determined. RESULTS: The QLV theory was found to be applicable for the time range that is relevant for pedestrian-automobile collisions. The structural behavior of the knee ligaments was found to be particularly rate-sensitive for high elongation rates, as occur during these collisions. The ligament stiffness was found to increase with age for both the collateral ligaments and with weight for the medial collateral ligament. CONCLUSIONS: For the loading conditions that are relevant for pedestrian-automobile collisions, the use of the QLV model for the description of the mechanical behavior of knee ligaments is appropriate. The rate-sensitivity is particularly important for these extreme loading conditions. The relaxation behavior was found to be consistent between different ligament types and samples. Variations due to donor anthropometry were found predominantly for the instantaneous elastic behavior.

Dynamic bending tolerance and elastic-plastic material properties of the human femur.

The objective of this study was to provide data on the structural tolerance and material properties of the human femur in dynamic bending. Fifteen (15) isolated femurs from eight (8) males were tested in either posterior-to-anterior or lateral-to-medial three-point bending. The failure moment was 458 +/- 95 Nm and did not differ significantly with loading direction. A method was developed to estimate the elastic-plastic material properties of the bone using both force-deflection data and strain gauge measurements. The bone material appeared to yield at about one third of the ultimate strain level prior to fracture. It is hoped that these data will aid in the development of injury criteria and finite element models for predicting injuries to pedestrians and vehicle occupants.

A structural model for the ternary cleavable complex formed between human topoisomerase I, DNA, and camptothecin.

Using the X-ray crystal structure of the human topoisomerase I (TOP1)-DNA cleavable complex, we have developed a general model for the ternary drug-DNA-TOP1 cleavable complex formed with camptothecin (CPT) and its analogues. This model has the drug intercalated between the -1 and +1 base pairs, with the E-ring pointing into the minor groove and the A-ring directed toward the major groove. The ternary complex is stabilized by an array of hydrogen bonding and hydrophobic interactions between the drug and both the enzyme and the DNA. Significantly, the proposed model is consistent with the current body of experimental mutation, cross-linking, and structure-activity data. In addition, the model reveals potential sites of interaction that can provide a rational basis for the design of next generation compounds as well as for de novo drug design.

Ascobotryozyma americana gen. nov. et sp. nov. and its anamorph Botryozyma americana, an unusual yeast from the surface of nematodes.

A new teleomorphic genus Ascohotryozyma, with a single species, A. americana, is proposed. Its anamorph is a Botryozyma that differs from the type species, B. nematodophila, on distributional, physiological, and molecular criteria; it is described as Botryozyma americana, anam. sp. nov. Ascobotryozyma is characterized by globose asci bearing four lunate ascospores. Fusion of thallus cells precedes ascus formation. Ascobotryozyma americana was isolated from the surface of nematodes (Panagrellus dubius) associated with galleries of the poplar borer (Saperda calcarata) in trembling aspen (Populus tremuloides) in eastern Washington, USA. The teleomorph has not been produced in pure culture.

6-Acylamino-2-1[(ethylsulfonyl)oxy]-1H-isoindole-1,3-diones mechanism-based inhibitors of human leukocyte elastase and cathepsin G: effect of chirality in the 6-acylamino substituent on inhibitory potency and selectivity.

Inhibition of human leukocyte elastase(HLE) by a series of 6-acylamino-2-[(ethylsulfonyl)oxy)]-1H-isoindole-1,3-diones was determined and compared to their inhibition of ChT, PPE, and Cat G. The best inhibitor of the series was 6-((1'S)-camphanyl)amino-2-[(ethylsulfonyl) oxy]-1H-isoindole-1,3-dione 5b, with a k(obs)/[I] = 11,000 M(-1) s(-1). This study revealed that HLE shows a preference for the S stereochemistry and tolerates hydrophobic substituents in the Sn' binding sites. Molecular modeling of non-covalent HLE-inhibitor complexes was used as a tool to investigate our binding model. Buffer stability assays reveal that these compounds are susceptible to hydrolysis at physiological pH.

Matrix turnover.

This review concentrates on how the major component of extracellular matrix, collagen, is catabolized. This process is important in a number of aspects of orthodontics since matrix is constantly turning over, the rate of which differs in embryogenesis, ageing, disease, and physiological processes, such as orthodontic tooth movement. It is not the purpose of this review to consider each process in detail. The aim is to give a clear account of the matrix metalloproteinases (a major family of proteinases) including their classification, properties, and functions.

Ganaxolone for treating intractable infantile spasms: a multicenter, open-label, add-on trial.

This is a multicenter, open-label, add-on trial, investigating the safety and efficacy of ganaxolone (GNX) in a population of children with refractory infantile spasms, or with continuing seizures after a prior history of infantile spasms. A total of 20 children aged 7 months to 7 years were enrolled in this dose-escalation study, after baseline seizure frequencies were established. Concomitant antiepilepsy drugs were maintained throughout the study period. The dose of GNX was progressively increased to 36 mg/kg/d (or to the maximally tolerated dose) over a period of 4 weeks, then maintained for 8 weeks before tapering and discontinuation. Seizure diaries were maintained by the families, and spasm frequency was compared with the baseline period. The occurrence of adverse events was clinically monitored, and global evaluations of seizure severity and response to treatment were obtained. A total of 16 of the 20 subjects completed the study, 15 of whom had refractory infantile spasms at the time of study enrollment. Spasm frequency was reduced by at least 50% in 33% of these subjects, with an additional 33% experiencing some improvement (25-50% reduction in spasm frequency). Ganaxolone was well tolerated, and adverse events attributed to GNX were generally mild. Ganaxolone was safe and effective in treating this group of refractory infantile spasms patients in an open-label, add-on trial. Further investigation with randomized, controlled study design is warranted.

Temporal changes in collagen composition and metabolism during rodent palatogenesis.

Cleft lip and palate is a common craniofacial malformation in man. The aetiology is multifactorial and not known. Since collagen is a major structural component of the developing palate, we studied its composition and metabolism during palate shelf formation and elevation in the rat. Palatal shelves were harvested at embryonic days (E) 15, 16 and 17 as well as post-partum. Palatal collagen increased threefold from E15 to E17 and tenfold from E17 to 5-day-old pups. Palatal calcification was seen in the main, post-partum. Collagen cross-linking, which may be important in shelf elevation and union, varied. The concentration of hydroxylysyl-pyridinolone cross-links was greatest prior to shelf elevation, declining thereafter. Similarly, the highest concentration of dihydroxylysinononorleucine was seen at E16 and this supports the concept of a compliant mesenchymal shelf responding to an intrinsic elevating force. We then determined if enzymes responsible for matrix degradation, matrix metalloproteinases (MMP) and the tissue inhibitors of metalloproteinases (TIMPs) altered over the same time periods. MMP-2, and TIMP-1 and TIMP-2 were identified by gelatin zymography and reverse zymography, respectively. MMP-3 activity was determined with a fluorogenic substrate assay. TIMP-1, TIMP-2 and MMP-3 levels remained constant from E15 to E17. The MMP-2 levels showed a significant elevation from E15 to E16 and E16 to E17. This suggests the regulation of extracellular matrix is likely to be of importance in palate morphogenesis.

Adjunctive therapy with oxcarbazepine in children with partial seizures. The Oxcarbazepine Pediatric Study Group.

OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) as adjunctive therapy in children with inadequately controlled partial seizures on one or two concomitant antiepileptic drugs (AEDs). BACKGROUND: OXC has shown antiepileptic activity in several comparative monotherapy trials in newly diagnosed patients with epilepsy, and in a placebo-controlled monotherapy trial in hospitalized patients evaluated for epilepsy surgery. DESIGN: A total of 267 patients were evaluated in a multicenter, randomized, placebo-controlled trial consisting of three phases: 1) a 56-day baseline phase (patients maintained on their current AEDs); 2) a 112-day double-blind treatment phase (patients received either OXC 30-46 mg/kg/day orally or placebo); and 3) an open-label extension phase. Data are reported only from the double-blind treatment phase; the open-label extension phase is ongoing. METHODS: Children (3 to 17 years old) with inadequately controlled partial seizures (simple, complex, and partial seizures evolving to secondarily generalized seizures) were enrolled. RESULTS: Patients treated with OXC experienced a significantly greater median percent reduction from baseline in partial seizure frequency than patients treated with placebo (p = 0.0001; 35% versus 9%, respectively). Forty-one percent of patients treated with OXC experienced a > or =50% reduction from baseline in partial seizure frequency per 28 days compared with 22% of patients treated with placebo (p = 0.0005). Ninety-one percent of the group treated with OXC and 82% of the group treated with placebo reported > or =1 adverse event; vomiting, somnolence, dizziness, and nausea occurred more frequently (twofold or greater) in the group treated with OXC. CONCLUSION: OXC adjunctive therapy administered in a dose range of 6 to 51 mg/kg/day (median 31.4 mg/kg/day) is safe, effective, and well tolerated in children with partial seizures.