bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of birthweight discordance in the intellectual and motor outcome for triplets at early school age
Authors: NATALUCCI GIANCARLO , SEITZ JOCHEN , SIEBENTHAL KURT VON , BUCHER HANS U , MOLINARI LUCIANO , JENNI OSKAR G , LATAL BEATRICE
Published: June 2011

Aim  We assessed motor and intellectual outcome in triplets at school age and investigated the predictive value of perinatal and demographic factors.

Methods  Seventy‐one live‐born newborn infants (24 triplet pregnancies) were prospectively enrolled at birth. At the age of 6 years, 58 children (31 males, 27 females; mean gestational age 31.2wks [SD 2.2wks]; mean birthweight 1622g [SD 440g]) returned for a neurodevelopmental examination. A comparison group for triplets born before 32 gestational weeks comprising 26 gestational age‐, birthweight‐, and sex‐matched singletons was also recruited (mean gestational age 30.1wk [SD 1.5wk]; mean birthweight 1142g [SD 210g]; 12 males, 14 females). The Zurich Neuromotor Assessment was used to examine motor performance, and intellectual abilities were assessed with the Kaufman Assessment Battery for Children (K‐ABC).

Results  Motor performance and movement quality in these individuals was significantly reduced compared with the test norms for all motor tasks (p<0.001) other than static balance. The mean values on the Mental Processing Composite (95.3, SD 8.4) and the Achievement Scale (90.1, SD 13.8) of the K‐ABC were also lower than those in the test reference (p<0.05 and p<0.01 respectively). Triplets born at less than 32 weeks’ gestation showed poorer pure motor and adaptive gross motor performance (both p<0.05) than, but similar intellectual performance to, the gestational age‐, birthweight‐ and sex‐matched singletons. Poor outcome was predicted by low socio‐economic status and by intertriplet birthweight discordance (both p<0.01).

Interpretation  Triplets were at an increased risk of mild motor and intellectual impairments. This finding is important for tailoring therapeutic interventions for these children and for parental counselling. Very preterm triplets showed similar outcomes to the singleton comparison children, except that they had poorer motor performance. Low socio‐economic status was a major risk factor for impaired intellectual development. In addition, birthweight discordance may also be considered a predictor for poor long‐term motor and intellectual outcome in triplets.
Additional learning needs policy in the devolved polities of the UK: a systems perspective
Authors: Chaney Paul
Published: June 2011

Using a systems approach, this paper explores the impact of devolution on additional learning needs (ALN) policy in compulsory phase education. Focus is placed on ALN/SEN Codes of Practice, the schools curriculum, teacher training, and the work of education inspectorates and tribunals. Analysis reveals that the move to quasi‐federalism in the UK has led to a raft of territorially specific policies and resulted in contrasting legal rights for pupils and parents. The prevailing policy discourse is one of equality, inclusion and informed choice. Against this background, and with a number of reforms ongoing, there is evidence of progress in embedding measures to address ALN in the respective education systems. Notwithstanding this, analysis of the first decade of devolved policy and practice also reveals a number of shortcomings and challenges, including limitations in data‐gathering and staff training – as well as questions about the level of cohesion between the three elements of education provision identified by systems analysis.
Okadaic acid induces matrix metalloproteinase‐9 expression in fibroblasts: crosstalk between protein phosphatase inhibition and β‐adrenoceptor signalling
Authors: Rietz A , Volkov Y , Davies A , Hennessy M , Spiers JP
Published: June 2011

BACKGROUND AND PURPOSE Interactions between protein phosphatase inhibition and matrix metalloproteinase (MMP)‐9 expression have implications for tissue remodelling after injury. Stimulation of β‐adrenoceptors could affect such interactions as isoprenaline increases protein phosphatase 2A (PP2A) activity and MMP‐9 abundance. We investigated the effect of okadaic acid (OA) on MMP‐9 expression to assess interactions between phosphatase inhibition and β‐adrenoceptor signalling in fibroblasts.

EXPERIMENTAL APPROACH Fibroblasts were exposed to OA alone and in combination with isoprenaline. Effects on MMP‐9 expression and intracellular signalling were studied using promoter assays, Western blot analysis and siRNA methodologies.

KEY RESULTS Okadaic acid increased MMP‐9 abundance in human cardiac ventricular fibroblasts, NIH3T3 fibroblasts and hepatic stellate cells. This effect was unaffected by PP2A knockdown in NIH3T3 cells. OA increased phosphorylation of NF‐κB, but not NF‐κB promoter activity, IκBα degradation, or nuclear translocation of p65‐NF‐κB. Exposure to SB202190 (p38 MAPK), U0126 (ERK1/2) and NF‐κB III inhibitor revealed that OA induced MMP‐9 activity through p38 MAPK. Isoprenaline inhibited OA‐mediated MMP‐9 expression in NIH3T3, in a β‐arrestin 2‐ and PP2A‐dependent manner. Mutation of the activator protein‐1 (AP‐1) and NF‐κB binding sites demonstrated that OA‐induced MMP‐9 activity was mediated through the AP‐1 but not NF‐κB sites. The latter mediated the inhibitory effect of isoprenaline on OA‐induced MMP‐9 promoter activity.

CONCLUSION AND IMPLICATIONS Okadaic acid induced MMP‐9 activity through p38 MAPK and was inhibited by isoprenaline via a pathway involving β‐arrestin 2, PP2A and an NF‐κB binding motif. These findings elucidate how phosphoprotein phosphatases and adrenoceptors may modulate tissue remodelling by affecting fibroblast function.
Amplified NO/cGMP‐mediated relaxation and ryanodine receptor‐to‐BKCa channel signalling in corpus cavernosum smooth muscle from phospholamban knockout mice
Authors: Joshi Shreena , Nelson Mark T , Werner Matthias E
Published: June 2011

BACKGROUND AND PURPOSE Relaxation of corpus cavernosum smooth muscle (CCSM) is induced by NO. NO promotes the formation of cGMP, which activates cGMP‐dependent protein kinase I (PKGI). The large conductance calcium‐activated potassium (BKCa) channel is regarded as a major target of NO/cGMP signalling; however, the mechanism of BKCa activation remains unclear. The aim of the present study was to determine whether sarcoplasmic reticulum (SR) Ca2+ load and Ca2+ release from the SR via ryanodine receptors (RyRs) is important for BKCa channel activation in response to NO/cGMP.

EXPERIMENTAL APPROACH In vitro myography was performed on CCSM strips from wild‐type and PLB knockout (PLB−/−) mice to evaluate contraction and relaxation in response to pharmacological agents and electrical field stimulation (EFS).

KEY RESULTS In CCSM strips from PLB−/− mice, a model of increased SR Ca2+ load, contractile force in response to EFS or phenylephrine (PE) was increased by nearly 100%. EFS of strips precontracted with PE induced transient relaxation in CCSM, an effect that was significantly larger in PLB−/− strips. Likewise, the relaxation of PE‐induced contraction in response to SNP and cGMP was greater in PLB−/−, as demonstrated by a shift in the concentration–response curve towards lower concentrations. Blocking RyRs and BKCa channels diminished the induced relaxations and eliminated the difference between wild‐type and PLB−/−.

CONCLUSIONS AND IMPLICATIONS NO/cGMP activates BKCa channels through RyR‐mediated Ca2+ release. This signalling pathway is responsible for approximately 40% of the NO/cGMP effects and is amplified by increased SR Ca2+ concentrations.
Translational approaches targeting the p53 pathway for anti‐cancer therapy
Authors: Essmann Frank , Schulze‐Osthoff Klaus
Published: June 2011

The p53 tumour suppressor blocks cancer development by triggering apoptosis or cellular senescence in response to oncogenic stress or DNA damage. Consequently, the p53 signalling pathway is virtually always inactivated in human cancer cells. This unifying feature has commenced tremendous efforts to develop p53‐based anti‐cancer therapies. Different strategies exist that are adapted to the mechanisms of p53 inactivation. In p53‐mutated tumours, delivery of wild‐type p53 by adenovirus‐based gene therapy is now practised in China. Also, remarkable progress has been made in the development of p53‐binding drugs that can rescue and reactivate the function of mutant or misfolded p53. Other biologic approaches include the development of oncolytic viruses that are designed to specifically replicate in and kill p53‐defective cells. Inactivation of wt‐p53 frequently results from dysregulation of MDM2, an E3 ligase that regulates p53 levels. Small‐molecule drugs that inhibit the interaction of MDM2 and p53 and block p53 degradation are currently tested in clinical trials. This survey highlights the recent developments that attempt to modulate the function of p53 and outlines strategies that are being investigated for pharmacological intervention in the p53 pathway.
Aspen and Willow Restoration Using Beaver on the Northern Yellowstone Winter Range
Authors: McColley Samuel D. , Tyers Daniel B. , Sowell Bok F.
Published: June 2011

Aspen (Populus tremuloides) on the northern Yellowstone winter range has declined over the last half‐century. Beaver (Castor canadensis) were reintroduced in Eagle Creek in 1991 in an attempt to reverse this trend. In 2005, we assessed the efficacy of this project by quantifying the long‐term effects of beaver on aspen stands and the riparian area in this drainage. Between 1990 and 2005, the canopy cover of mature aspen decreased more than 62%, whereas immature aspen cover more than tripled, resulting in a total aspen canopy cover decrease (p< 0.05) from 43 to 25% (a loss of 7.25 ha). Willow canopy cover increased from 10 to 14% during the same period. The impacts of beaver on aspen stands were estimated by comparing vegetative changes among control sites with less than 10% beaver use (n= 5), active beaver sites (n= 6), sites inactive for 1–3 years (n= 7), sites inactive for 4–6 years (n= 4), and sites inactive for 7–11 years (n= 5). Aspen sprout and sapling densities were greater (p= 0.01) on sites which were active and inactive for 1–3 years compared to the other sites. Aspen ramets were not able to grow taller than 2 m on sites without beaver activity for 4–11 years due to ungulate herbivory. Although beaver stimulated the growth of aspen sprouts and saplings, ungulate herbivory prevented successful aspen recovery in the Eagle Creek drainage of the northern Yellowstone winter range 14 years after beaver reintroduction.
American Chestnut Past and Future: Implications of Restoration for Resource Pulses and Consumer Populations of Eastern U.S. Forests
Authors: Dalgleish Harmony J. , Swihart Robert K.
Published: June 2011

Forests dominated by oak, beech, hornbeam, and boreal conifers are characterized by resource pulses. Contemporary eastern U.S. oak forests may exhibit dramatic resource pulses in part because of the loss of American chestnut, which comprised 25–50% of the canopy throughout its range. Chestnut loss may have reduced mast resources for wildlife. A newly developed, blight‐resistant hybrid makes reintroduction feasible within several years. We use historical data to model the effects of American chestnut mast on consumer populations, illuminating the potential ecological effects of a successful restoration. We parameterized a stochastic population growth model with mast production data to compare consumer population dynamics both pre‐ and post‐blight. We explored the effect of maximum intrinsic population growth rate, degree of density dependence, and reliance upon mast on consumer response to chestnut loss. We parameterized the models for white‐footed mouse, eastern chipmunk, gray squirrel, and white‐tailed deer. At a northern site 14 years post‐blight, simulated annual mast production decreased 80% and the coefficient of variation (CV) increased 60%. At a southern site 35 years post‐blight, annual mast production decreased by 35% and the CV increased by 76%. Smaller, more variable mast crops translated to reduced abundance and increased variability in simulated consumer populations. White‐footed mice were the most responsive, exhibiting a 48% decrease in population size and 57% increase in interannual variation post‐blight. The reintroduction of blight‐resistant chestnut may fundamentally alter predator–prey interactions, gypsy moth outbreaks, and Lyme disease hot spots through its effect on the character of resource pulses that drive consumer dynamics.
The Shifting of Ecological Restoration Benchmarks and Their Social Impacts: Digging Deeper into Pleistocene Re‐wilding
Authors: Toledo David , Agudelo Marta S. , Bentley Amanda L.
Published: June 2011

Current and projected rates of species loss prompt us to look for innovative conservation efforts. One such proposal is that large areas of North America be re‐wilded with old world species that descended from Pleistocene mega‐fauna. We argue that this approach overlooks many important ecological, evolutionary, cultural, and economic issues and detracts from conservation efforts by adding another arbitrary restoration benchmark. Our objectives are to specifically address the shifting benchmark for ecological restoration, explore the social dimensions of Pleistocene re‐wilding, which have been largely overlooked, and discuss why we think Pleistocene re‐wilding is not a proactive approach for conservation. This is not intended as a critique of innovative approaches. Instead it is an argument that human and ecological factors need to be considered in depth before any restoration initiative can be practically implemented. Proactive approaches should consider historical conditions while managing based on the present, should plan for the future, and should allow adaptation to changing conditions. We support the strategy to restore ecological interactions using species that coevolved with these interactions, bearing in mind the complexities of the socio‐ecological dimensions of any management action.
An Assessment of Introductory Restoration Courses in the United States and Canada
Authors: Bakker Jonathan D. , Howell Justin
Published: June 2011

A considerable number of institutions offer courses in restoration ecology and its application, ecological restoration. We quantified the scope and structure of introductory restoration courses at 67 post‐secondary institutions by reviewing institutional course catalogs and course syllabi. Most courses were available at Research‐level institutions. More than half of the courses were offered within departments that focused on natural resource management, and were required or optional in a degree program. Most courses were taught in classroom settings during the academic year and were geared toward advanced students. Course titles suggested an emphasis on the science of restoration ecology over the practice of ecological restoration, and learning objectives focused primarily on concepts and less on skills and attitudes. Assessment was largely via conventional methods, notably exams. Many courses assigned readings from the primary literature; there was little consensus in terms of text selection. We conclude that restoration is being presented to students as an advanced undertaking and in largely theoretical terms. Although we were unable to consider other important elements such as thematic content, class size, or pedagogical method, our study provides a baseline assessment of introductory restoration courses that can be used to evaluate changes in restoration education or opportunities for restoration education in other countries. These results can inform the development of new introductory restoration courses, and raise important considerations in light of the development of a Practitioners' Certification Program by the Society for Ecological Restoration.
Investigating Predictors of Plant Establishment During Roadside Restoration
Authors: Haan Nathan L. , Hunter MaryCarol R. , Hunter Mark D.
Published: June 2011

Ecological restoration on roadsides confers several ecological benefits, but also poses significant challenges. Native plants used in restoration efforts must survive compacted soil, harsh microclimates, prolific invasive species, and pollution from road salts and vehicle emissions. Criteria for both site and species selection need to be developed to assist practitioners in restoring roadside environments. We transplanted seedlings of 9 grassland plant species into plots within 8 highway interchanges surrounding Ann Arbor, Michigan, United States. To see if they might predict plant performance in roadside restoration, we assessed 2 indices: the coefficient of conservatism (CC) as an index of affinity to undisturbed habitat; and the number of U.S. counties in which each species occurs as an index of distribution. We measured seedling survival, height, and biomass during the first growing season, and survival 1 year after transplant. We also measured soil characteristics, air temperature, and humidity at each interchange. We found that soil characteristics largely determined plant survival. Plants were more likely to survive in sandier soils than in soils rich in silt or clay that had high bulk density, high pH, and high conductivity. Although plant survival varied among species and interchanges, neither CC nor county‐level distribution was a useful predictor of survival. Our results illustrate the importance of matching plant species with local soil characteristics when choosing restoration sites, and offer guidance to transportation officials considering roadside restoration with native plants, and practitioners working to restore any heavily disturbed site.
Anesthesia and Postoperative Delirium in Older Adults Undergoing Hip Surgery
Authors: Slor Chantal J. , de Jonghe Jos F.M. , Vreeswijk Ralph , Groot Erwin , Ploeg Tjeerd V.D. , van Gool Willem A. , Eikelenboom Piet , Snoeck Marc , Schmand Ben , Kalisvaart Kees J.
Published: June 2011

OBJECTIVES: To examine the effects of general anesthesia on the risk of incident postoperative delirium in older adults undergoing hip surgery.

DESIGN: Secondary analysis of haloperidol prophylaxis for delirium clinical trial data. Predefined risk factors for delirium were assessed prior to surgery. Primary outcome was postoperative delirium. Study outcome was compared across patient groups who received either general or regional anesthesia, and for individuals receiving various perioperative medications (benzodiazepines, anticholinergics, and opioids), using multivariable logistic regression after controlling for potential confounders. Subgroup analyses based on baseline cognitive impairment and delirium risk were also undertaken.

SETTING: Large medical school‐affiliated general hospital in Alkmaar, the Netherlands.

PARTICIPANTS: Five hundred twenty‐six adults aged 70 and older undergoing hip surgery.

MEASUREMENTS: The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria).

RESULTS: Sixty participants (11.4%) had incident postoperative delirium. One hundred eighty‐nine (35.9%) received general anesthesia, 18 (9.5%) of whom developed postoperative delirium, and 337 (64.1%) received regional anesthesia, 42 (12.5%) of whom developed postoperative delirium (adjusted odds ratio=0.81, 95% confidence interval=0.43–1.52, P=.51). Results were stratified for baseline cognitive impairment, age, acute admission, perioperative medication and other delirium risk factors. Delirium was not independently associated with specific drugs or the medication classes opioids, benzodiazepines, and anticholinergics.

CONCLUSION: General anesthesia has no distinct effect on incident postoperative delirium in older adults undergoing hip surgery. This also holds for individuals suffering from cognitive impairment or who are otherwise at risk for postoperative delirium. Perioperative use of narcotics, benzodiazepines, and anticholinergic agents was not associated with incident delirium in this cohort of older adults undergoing hip surgery.
A Randomized Controlled Clinical Trial of the Seattle Protocol for Activity in Older Adults
Authors: Teri Linda , McCurry Susan M. , Logsdon Rebecca G. , Gibbons Laura E. , Buchner David M. , Larson Eric B.
Published: June 2011

OBJECTIVES: To compare the efficacy of a physical activity program (Seattle Protocol for Activity (SPA)) for low‐exercising older adults with that of an educational health promotion program (HP), combination treatment (SPA+HP), and routine medical care control conditions (RMC).

DESIGN: Single‐blind, randomized controlled trial with two‐by‐two factorial design.

SETTING: Community centers in King County, Washington, from November 2001 to September 2004.

PARTICIPANTS: Two hundred seventy‐three community‐residing, cognitively intact older adults (mean age 79.2; 62% women).

INTERVENTIONS: SPA (in‐class exercises with assistance setting weekly home exercise goals) and HP (information about age‐appropriate topics relevant to enhancing health), with randomization to four conditions: SPA only (n=69), HP only (n=73), SPA+HP (n=67), and RMC control (n=64). Active‐treatment participants attended nine group classes over 3 months followed by five booster sessions over 1 year.

MEASUREMENTS: Self‐rated health (Medical Outcomes Study 36‐item Short‐Form Survey) and depression (Geriatric Depression Scale). Secondary ratings of physical performance, treatment adherence, and self‐rated health and affective function were also collected.

RESULTS: At 3 months, participants in SPA exercised more and had significantly better self‐reported health, strength, and general well‐being (P<.05) than participants in HP or RMC. Over 18 months, SPA participants maintained health and physical function benefits and had continued to exercise more than non‐SPA participants. SPA+HP was not significantly better than SPA alone. Better adherence was associated with better outcomes.

CONCLUSION: Older adults participating in low levels of regular exercise can establish and maintain a home‐based exercise program that yields immediate and long‐term physical and affective benefits.
Cerebrospinal Fluid β‐Amyloid and Tau Are Not Associated with Risk of Delirium: A Prospective Cohort Study in Older Adults with Hip Fracture
Authors: Witlox Joost , Kalisvaart Kees J. , de Jonghe Jos F.M. , Verwey Nicolaas A. , van Stijn Mireille F.M. , Houdijk Alexander P.J. , Traast Han S. , MacLullich Alasdair M.J. , van Gool Willem A. , Eikelenboom Piet
Published: June 2011

OBJECTIVES: To examine the association between cerebrospinal fluid (CSF) β‐amyloid (Aβ1–42), tau, and hyperphosphorylated tau (Ptau) and risk of delirium in older adults with hip fracture.

DESIGN: Prospective cohort study.

SETTING: University‐affiliated general hospital in Alkmaar, the Netherlands.

PARTICIPANTS: Seventy‐six participants aged 75 and older admitted for surgical repair of acute hip fracture.

MEASUREMENTS: Presurgical baseline screening and assessment included the Informant Questionnaire on Cognitive Decline—short form (IQCODE‐N), Mini‐Mental State Examination, standardized Snellen test for visual impairment, Geriatric Depression Scale, Barthel Index (BI), and Lawton Instrumental Activity of Daily Living (IADL) scale. The number of medical comorbidities and medications at home, American Society of Anesthesiologists score, and Acute Physiology and Chronic Health Evaluation II score were determined according to chart review. Delirium was diagnosed using the Confusion Assessment Method. CSF was collected at the onset of spinal anesthesia.

RESULTS: Postoperative delirium occurred in 30 (39.5%) participants. Participants with delirium were older, showed more signs of cognitive decline, were more dependent at home in activity of daily living and IADL functioning, and used more medications before admission. Preoperative CSF Aβ1‐42, tau, and Ptau levels were not significantly different in participants who did and did not develop delirium during subsequent hospitalization. In contrast, prefracture cognitive decline (IQCODE‐N) was significantly related to delirium (odds ratio=9.43, 95% confidence interval=2.45–36.31).

CONCLUSION: Cognitive impairment predisposes to delirium, but in this study, postoperative delirium was not associated with baseline CSF Aβ1‐42, tau, and Ptau levels. These findings suggest that CSF markers for plaque and tangle formation are not strongly associated with delirium risk in older adults with hip fracture.
Forced Expiratory Volume in 1 Second and Cognitive Aging in Men
Authors: Weuve Jennifer , Glymour M. Maria , Hu Howard , Sparrow David , Spiro Avron , Vokonas Pantel S. , Litonjua Augusto A.
Published: June 2011

OBJECTIVES: To evaluate forced expiratory volume in 1 second (FEV1, a measure of overall lung function), long‐term average FEV1, and rate of decline in FEV1 in relation to cognition and cognitive decline in older men.

DESIGN: Prospective observational study.

SETTING: Community‐based population.

PARTICIPANTS: Eight hundred sixty‐four older men from the Normative Aging Study.

MEASUREMENTS: Starting in 1984, participants underwent triennial clinical evaluations. Lung function assessments provided estimates of FEV1. Cognitive assessments entailing tests of several cognitive abilities began in 1993. FEV1 measured approximately 12 years before baseline cognitive testing, average FEV1 over the 12‐year period, and rate of change in FEV1 were all evaluated in relation to baseline and change in performance on the cognitive tests.

RESULTS: In multivariable‐adjusted analyses, associations between FEV1 and baseline cognitive scores were mixed, although average FEV1 predicted significantly better performance on tests of visuospatial ability (P=.04) and general cognition (P=.03). Higher FEV1 was more consistently associated with slower cognitive decline, but only the association between historical FEV1 and attention was significant (difference per standard deviation in FEV1=0.056, P=.05). Rate of FEV1 decline was not consistently associated with cognitive function or decline. Findings were generally similar or stronger in men who had never smoked. To account for potential bias due to selective attrition, inverse probability of censoring weights were applied to the cognitive decline analyses, yielding slightly larger estimates; the inadequate prognostic power of the censoring models limited this approach.

CONCLUSION: Overall, the data provide limited evidence of an inverse association between FEV1 and cognitive aging.
The Vulnerable Elders Survey‐13 Predicts Hospital Complications and Mortality in Older Adults with Traumatic Injury: A Pilot Study
Authors: Min Lillian , Ubhayakar Nitin , Saliba Debra , Kelley‐Quon Lorraine , Morley Eric , Hiatt Jonathan , Cryer Henry , Tillou Areti
Published: June 2011

OBJECTIVES: To determine whether the Vulnerable Elders Survey (VES)‐13, a survey based on functional status that has been validated in uninjured older populations, will predict complications and mortality in injured older adults.

DESIGN: Prospective observational pilot study.

SETTING: Level 1 trauma center.

PARTICIPANTS: Sixty‐three older adults (≥65) with a traumatic injury who survived and required inpatient care for at least 24 hours.

MEASUREMENTS: Predictor: preinjury VES‐13 score (0–10 points, higher=greater risk) obtained by interviewing participants or proxies. Outcomes: composite outcome of one or more medical complications (e.g., aspiration pneumonia, respiratory failure) or death, discharge destination (home, nursing home, death), length of stay, hospital charges. Covariates: Charlson Comorbidity Index (CCI), Injury Severity Score (ISS), and sex.

RESULTS: Of the 63 participants, 30 (48%) were discharged to home and 28 (44%) to a nursing facility, 21 (33%) developed one or more complications, and four (6%) died. In a model that also controlled for ISS and comorbidity, each additional VES‐13 point was associated with greater risk of complication or death (odds ratio=1.53 per point, 95% confidence interval=1.12–2.07).

CONCLUSION: The VES‐13, in combination with injury severity, may be useful early in the hospital course to predict complications and death in older adults with traumatic injury, potentially identifying candidates who may benefit from additional inpatient geriatric services.
Cognitive Impairment Predicts Fatal Incident Stroke: Findings from a National Sample of Older Adults
Authors: Clarke Philippa J. , Blount Vanessa , Colantonio Angela
Published: June 2011

OBJECTIVES: To investigate the effect of cognitive impairment on fatal and nonfatal incident stroke in older adults.

DESIGN: A large, national, prospective, population‐based study of a representative cohort of older Canadians followed over a 10‐year period.

SETTING: Secondary analyses were conducted using data from the Canadian Study of Health and Aging, a population‐based study of older adults followed prospectively from 1991 to 2001.

PARTICIPANTS: Nine thousand four hundred fifty‐one adults aged 65 and older who had not previously been diagnosed with stroke at baseline (in 1991).

MEASUREMENTS: In addition to known risk factors, the independent contribution of cognitive function (diagnosed in a clinical examination) was examined as a risk for stroke in older adults.

RESULTS: Multinomial logistic regression analyses showed that cognitive impairment was associated with twice the odds of fatal incident stroke, controlling for well‐established risk factors.

CONCLUSION: This study provides further evidence for the need to consider cognitive function in relation to stroke risk in older populations.
The Orientation Distributions of Lines, Surfaces, and Interfaces around Three‐Phase Boundaries in Solid Oxide Fuel Cell Cathodes
Authors: Dillon Shen J. , Helmick Lam , Miller Herbert M. , Wilson Lane , Gemman Randall , Petrova Rumyana V. , Barmak Katayun , Rohrer Gregory S. , Salvador Paul A.
Published: June 2011

Three‐dimensional electron backscatter diffraction was used to measure the crystallographic distribution of the electrochemically relevant triple phase boundary lines and surfaces near them in SOFC cathodes made up of a porous mixture of yttria‐stabilized zirconia and lanthanum strontium manganese oxide, both before and after mild electrochemical loading. All distributions were observed to be nearly isotropic, but non‐random textures above the detection threshold were observed. The distributions differ between the two cells, as do the phase fractions and the electrochemical history. The different distributions are interpreted as evidence that steady‐state distributions vary locally with phase fractions or that they evolve during the initial operation of the fuel cell. The rates at which triple lines, pore surfaces, and interface boundaries in the porous mixture approach a steady‐state value appear to decrease with the average amount of mass transport required to reorient that specific feature. This work provides initial insights into the crystallography of interfaces in a multiphase ceramic material.
Preparation of Sizable and Uniform‐Sized Spherical Ceramic Foams: Drop‐in‐Oil and Agar Gelation
Authors: Han Yosep , Kim Seongmin , Kim Hyunjung , Park Jaikoo
Published: June 2011

We propose a simple and environmentally friendly method to prepare uniform‐sized spherical ceramic foams (SCFs) with excellent pore properties by combining a drop‐in‐oil method with agar gelation. In addition, the change in size distribution and uniformity (characterized as coefficient of variation (C.V.)) and the corresponding pore‐related properties for the SCFs were systematically investigated as functions of agar concentration (i.e., 0.50–1.50 wt% with respect to dry alumina). The results showed that uniform‐sized SCFs were successfully fabricated regardless of agar concentration, that pore‐related properties were gradually improved by increasing the agar content, and that the most uniform‐sized SCFs were obtained when the agar concentration was 1.00 wt%. The extent of the improvement in size uniformity was evaluated by comparing the C.V. value for the drop‐in‐oil method with that for the pseudo‐double‐emulsion (PDE) method, which is an alternative method to fabricate SCFs. The C.V. values for the SCFs prepared by the drop‐in‐oil and the PDE method were determined to be 7% and 31%, respectively. The results clearly indicate that the size uniformity of the SCFs has been much improved for the drop‐in‐oil method as compared to the PDE method.
A New Rapid Route for In Situ Synthesizing Monolithic TiB Ceramic
Authors: Zhang Zhaohui , Shen Xiangbo , Wang Fuchi , Lee Shukui
Published: June 2011

Fine‐grained monolithic TiB ceramics were successfully in situ synthesized by spark plasma sintering (SPS) technique at temperatures of 1150°–1450°C and a pressure of 50 MPa, using Ti and TiB2 as reactants. Mechanical properties and densification behavior of the TiB ceramics were investigated. The results indicate that TiB ceramic sintered at 1450°C provide the optimal combination of dense microstructure and excellent properties, including the relative density of 98.2%, the microhardness of 21.2 ± 1.8 GPa, the flexural strength of 548 ± 45 MPa and the fracture toughness of 5.9 ± 0.4 MPa·m1/2. The dense and fine‐grained microstructures are the main factors to improve the mechanical properties of the TiB ceramic synthesized by SPS process.
Glasses in theBa–Si–O–NSystem
Authors: Ali Sharafat , Jonson Bo
Published: July 2011

The preparation and properties ofBa–Si–O–Nglasses are reported. These oxynitride glasses were prepared by melting mixtures ofBaH2,SiO2, andSi3N4powders in a nitrogen atmosphere at 1550°–1700°C. The glasses were characterized by X‐ray powder diffraction, differential thermal analysis, and scanning electron microscopy. Final glass compositions were calculated from analyses obtained by energy dispersive X‐ray (EDX) spectroscopy and combustion analysis, for cation and anion compositions, respectively. The glasses were found to be homogenous, translucent gray to opaque black, and consists ofNcontents of up to 42 equiv% andBacontents of up to 36 equiv%. Determined glass densities varied between 3.27 and 4.18 g/cm3, and calculated molar volumes varied between 10.28 and 11.11 cm3/mol. Both density and molar volume increase withBacontent. Glass compactness (0.45–0.49), glass transition temperature (786°–905°C), and microhardness (7.93–9.56 GPa) were found to increase linearly with N content. The refractive index increased from 1.66 to 1.91 and was found to be strongly correlated with the amounts ofBaandN.
Ascent™: A Novel Balloon Microcatheter Device Used as the Primary Coiling Microcatheter of a Basilar Tip Aneurysm
Authors: Kirmani Jawad F. , Paolucci Ugo
Published: June 2011

Intracranial aneurysms undergoing balloon‐assisted endovascular repair are particularly challenging given the concurrent use of one or more catheters in addition to the primary coiling microcatheter. Here, we describe a previously unreported novel device where a balloon catheter was used as the primary coiling microcatheter, thereby eliminated the need for additional catheters. J Neuroimaging 2012;22:191‐193.
Analysis of T2 Intensity by Magnetic Resonance Imaging of Deep Gray Matter Nuclei in Multiple Sclerosis Patients: Effect of Immunomodulatory Therapies
Authors: Pawate Siddharama , Wang Lily , Song Yanna , Sriram Subramaniam
Published: June 2011

OBJECTIVE

To investigate differences in T2 intensity of deep gray matter (dGM) structures by magnetic resonance imaging (MRI) in multiple sclerosis (MS) patients undergoing various immunomodulatory therapies.

BACKGROUND

In MS, dGM T2 hypointensities by MRI are hypothesized to represent iron deposition and are known to be associated with worse disease stage as assessed by brain atrophy, cognitive and physical disability. The relation between immunotherapies and T2 intensity, however, has been not been investigated in detail.

METHODS

A total of 255 MS patients were stratified into those on no treatment (NON, n= 45), and those on immunomodulatory treatments for ≥6 months (ie, interferon beta [IFNβ]n= 118, glatiramer acetate [GA]n= 41, natalizumab [NAT]n= 39, and mycophenolate mofetil [MMF]n= 12). T2 intensities of dentate nucleus (DN), substantia nigra (SN), red nucleus (RN), and globus pallidus (GP) were measured. Group differences in T2 intensities were assessed using a linear regression model with T2 intensities as outcome variable, treatment group as main independent variable, and clinical measures such as Expanded Disability Status Scale (EDSS) score, years of MS, and 25‐feet walk time (T25‐FW) as covariates. To compare T2 intensities before and after treatment in a subset of NAT‐treated patients, we used the Wilcoxon signed‐rank test.

RESULTS

When adjusted for EDSS, duration of disease and T25‐FW, across all deep nuclei, NAT‐treated patients had significantly higher T2 intensities than untreated patients (DN p= 1.65 × 10−5; SN p= 2.37 × 10−5; RN p= 3.90 × 10−6; GP p= 1.05 × 10−6), IFNβ‐treated patients (DN p= 1.65 × 10−5; SN p= 2.37 × 10−5; RN p= 3.90 × 10−6; GP p= 1.05 × 10−6), and GA‐treated patients (DN p= 1.65 × 10−5; SN p= 2.37 × 10−5; RN p= 3.90 × 10−6; GP p= 1.05 × 10−6). In a subset of MS patients receiving NAT, there was a significant increase in T2 intensities in all the dGM nuclei after 24 months of treatment (DN p= 0.00021; SN p= <0.0001; RN p= 0.00015; GP p= 0.00011).

CONCLUSION

Our preliminary observations suggest that long‐term NAT therapy in MS patients may affect T2 intensity levels of dGM brain nuclei, hence suggesting a potential effect of NAT beyond anti‐inflammatory effect. Prospective studies are warranted to provide more insights into our preliminary observations. J Neuroimaging 2012;22:137‐144.
Melatonin alleviates cadmium‐induced cellular stress and germ cell apoptosis in testes
Authors: Ji Yan‐Li , Wang Hua , Meng Can , Zhao Xian‐Feng , Zhang Cheng , Zhang Ying , Zhao Mei , Chen Yuan‐Hua , Meng Xiu‐Hong , Xu De‐Xiang
Published: June 2011

Abstract: Increasing evidence demonstrates that melatonin has an anti‐apoptotic effect in somatic cells. However, whether melatonin can protect against germ cell apoptosis remains obscure. Cadmium (Cd) is a testicular toxicant and induces germ cell apoptosis. In this study, we investigated the effects of melatonin on Cd‐evoked germ cell apoptosis in testes. Male ICR mice were intraperitoneally (i.p.) injected with melatonin (5 mg/kg) every 8 hr, beginning at 8 hr before CdCl2(2.0 mg/kg, i.p.). As expected, acute Cd exposure resulted in germ cell apoptosis in testes, as determined by terminal dUTP nick‐end labeling (TUNEL) staining. Melatonin significantly alleviated Cd‐induced testicular germ cell apoptosis. An additional experiment showed that spliced form of XBP‐1, the target of the IRE‐1 pathway, was significantly increased in testes of mice injected with CdCl2. GRP78, an endoplasmic reticulum (ER) chaperone, and CHOP, a downstream target of the PERK pathway, were upregulated in testes of Cd‐treated mice. In addition, acute Cd exposure significantly increased testicular eIF2α and JNK phosphorylation, indicating that the unfolded protein response (UPR) pathway was activated by CdCl2. Interestingly, melatonin almost completely inhibited Cd‐induced ER stress and the UPR in testes. In addition, melatonin obviously attenuated Cd‐induced heme oxygenase (HO)‐1 expression and protein nitration in testes. Taken together, these results suggest that melatonin alleviates Cd‐induced cellular stress and germ cell apoptosis in testes. Melatonin may be useful as pharmacological agents to protect against Cd‐induced testicular toxicity.
Melatonin modulates autophagy through a redox‐mediated action in female Syrian hamster Harderian gland controlling cell types and gland activity
Authors: Vega‐Naredo Ignacio , Caballero Beatriz , Sierra Verónica , García‐Macia Marina , de Gonzalo‐Calvo David , Oliveira Paulo J. , Rodríguez‐Colunga María Josefa , Coto‐Montes Ana
Published: June 2011

Abstract:  The Syrian hamster Harderian gland exhibits sexually dimorphic porphyrin biosynthesis, wherein the female glands display an extraordinarily high concentration of porphyrins. Damage derived from this production of porphyrins, mediated by reactive oxygen species, causes the glands to develop autophagic processes, which culminate in detachment‐derived cell death; these cells normally play a central role in the secretory activity of the gland. The main aim of this study was to analyze how a change in the redox state impacts autophagy. Female Syrian hamsters were treated daily with melatonin (25 μg, subcutaneously) at ZT 10 for 1–2 months (N‐acetyl‐5‐methoxytryptamine), an endogenous antioxidant that ameliorates the deleterious effects of free radicals via a variety of mechanisms. The length of treatment affected the redox balance, the autophagy machinery, and the activation of p53 and NF‐κB. One‐month treatment displaces redox balance to the antioxidant side, promotes autophagy through a p53‐mediated mechanism, and increases cell detachment. Meanwhile, 2‐month treatment restores redox balance to the oxidant side, activates NF‐κB reducing autophagy to basal levels, increases number of type II cells, and reduces number of detached cells. Our results conclude that the redox state can modulate autophagy through redox‐sensitive transcriptions factors. Additionally, these findings support a hypothesis that ascribes differences in the autophagic‐lysosomal pathway to epithelial cell types, thereby restricting detachment‐induced autophagic cell death to epithelial cell type I.
CD39 Reveals Novel Insights into the Role of Transmembrane Domains in Protein Processing, Apical Targeting and Activity
Authors: Papanikolaou Agathi , Papafotika Alexandra , Christoforidis Savvas
Published: June 2011

Cargo proteins of the biosynthetic secretory pathway are folded in the endoplasmic reticulum (ER) and proceed to the trans Golgi network for sorting and targeting to the apical or basolateral sides of the membrane, where they exert their function. These processes depend on diverse protein domains. Here, we used CD39 (NTPdase1), a modulator of thrombosis and inflammation, which contains an extracellular and two transmembrane domains (TMDs), as a model protein to address comprehensively the role of native TMDs in folding, polarized transport and biological activity. In MDCK cells, CD39 exits Golgi dynamin‐dependently and is targeted to the apical side of the membrane. Although the N‐terminal TMD possesses an apical targeting signal, the N‐ and C‐terminal TMDs are not required for apical targeting of CD39. Folding and transport to the plasma membrane relies only on the C‐terminal TMD, while the N‐terminal one is redundant. Nevertheless, both N‐ and C‐terminal anchoring as well as genuine TMDs are critical for optimal enzymatic activity and activation by cholesterol. We conclude therefore that TMDs are not just mechanical linkers between proteins and membranes but are also able to control folding and sorting, as well as biological activity via sensing components of lipid bilayers.
Effects of mechanical stress on cytokine production in mandible‐derived osteoblasts
Authors: Yamamoto K , Yamamoto T , Ichioka H , Akamatsu Y , Oseko F , Mazda O , Imanishi J , Kanamura N , Kita M
Published: June 2011

Oral Diseases (2011) 17, 712–719

Objective:  Mechanical stress is known to be an important factor in the regulation of bone remodeling, and mandibular bone is continuously exposed to mechanical stressors such as occlusal force. Therefore, in this study, we investigated the effects of mechanical stress approaching occlusal force, to which mandible‐derived osteoblasts (MDOB) are exposed, on cytokine expression and production using an original hydrostatic pressure apparatus.

Materials and Methods:  The levels of cytokine in MDOB were examined by real‐time RT‐PCR, ELISA, and western blotting. In addition, mitogen‐activated protein kinase inhibitor for ERK1/2, JNK, and p‐38 pathways was used to identify the signal transduction pathway.

Results:  Hydrostatic pressure increased the expression of IL‐6 and TNF‐α mRNA in a magnitude‐ and time‐dependent manner and also enhanced IL‐6 and TNF‐α protein production. Furthermore, hydrostatic pressure changed the RANKL/OPG ratio in favor of RANKL for both mRNA and protein levels. Specific inhibitor of p‐38 pathway but not that of the ERK1/2 and JNK pathways suppressed the up‐regulation of RANKL production induced by hydrostatic pressure loading.

Conclusion:  These results suggest that MDOB play a role in cytokine production in response to mechanical stress and that occlusal force may support the maintenance of mandible bone homeostasis by activating bone remodeling through osteoclastogenesis.
Increased white matter integrity of posterior cingulate gyrus in the evolution of post-traumatic stress disorder
Authors: Zhang Li , Li Weihui , Shu Ni , Zheng Huirong , Zhang Zhijun , Zhang Yan , He Zhong , Hou Cailan , Li Zexuan , Liu Jun , Wang Lifeng , Duan Lian , Jiang Tianzi , Li Lingjiang
Published: June 2011

Objective:Functional imaging studies of post-traumatic stress disorder (PTSD) have shown an increased activation of posterior cingulate gyrus (PCG) of the brain. The aim of this study was to explore white matter integrity of PCG in PTSD subjects.

Methods:White matter integrity, as determined from fractional anisotropy (FA) value using diffusion tensor imaging, was assessed for PCG in subjects with and without PTSD from a severe mine accident. All subjects were also measured by the PTSD Checklist Civilian Version (PCL-C), the State-Trait Anxiety Inventory (STAI), the logical memory subtest and the visual reproduction subtest of the Wechsler Memory Scale-Revised in China. Sixteen PTSD subjects (8 subjects in each group) in the longitudinal study and 13 PTSD subjects as well as 14 non-PTSD controls in the cross-sectional case–control study were respectively recruited.

Results:In the longitudinal study, subjects with PTSD showed increased FA values in left PCG during the follow-up scan. In the cross-sectional study, FA values in bilateral PCG in PTSD subjects were higher than controls. Within the PTSD group (n= 13), FA values in the left PCG correlated positively with logical memory and negatively with PCL-C intrusion and STAI-trait (STAI-t) subscores. FA values in right PCG correlated negatively with STAI-t and STAI-state subscores.

Conclusion:These findings suggest that alterations of white matter integrity in PCG link to mnemonic and affective processing in PTSD over the long-term follow-up period.
Excessive activation of the loop between the NR2B subunit of the N-methyl-d-aspartate receptor and glycogen synthase kinase-3βin the hippocampi of patients with major depressive disorder
Authors: Oh Dong Hoon , Park Seon-Cheol , Park Yong Chon , Kim Seok Hyeon
Published: June 2011

Objective:We showed previously that glycogen synthase kinase-3β(GSK-3β) levels are significantly elevated in the hippocampi of patients with major depressive disorder (MDD). However, the exact cause of this elevation and its function are unknown. Recent animal studies have suggested a mechanism involving the N-methyl-d-aspartate (NMDA) NR2B–GSK-3βloop.

Methods:To investigate the existence of an NR2B–GSK-3βloop in the hippocampi of patients with MDD, we examined the expression of NR2B. We also attempted to identify markers that correlate with NR2B levels in the hippocampus, using the Stanley Neuropathology Consortium Integrative Database (SNCID). The SNCID is a web-based tool used to integrate Stanley Medical Research Institute (SMRI) data sets.

Results:We found that hippocampal levels of NR2B and DLGAP1 mRNA were higher in the MDD group (n= 8) than in unaffected controls (n= 12) (p< 0.05). NR2B expression levels were correlated with the expression levels of NR2A, NR1, DLGAP1, GSK-3βand nitric oxide synthase 1, as well as with the number of calretinin-immunoreactive neurons in the hippocampus in all subjects in the SNC (n= 42,p< 0.001).

Conclusion:The results of our study show the possible involvement of excessive activation of the NR2B–GSK-3βloop in the overexpression of GSK-3βin the hippocampi of patients with MDD.