bluuebunny/crossref_metadata_2025 huggingface dataset:
No arguments for increased endothelial nitric oxide synthase activity in migraine based on peripheral biomarkers
Authors: Van der Schueren Bart J , Verbrugge Frederik H , Verbesselt René , Hecken Anne Van , Depré Marleen , de Hoon Jan N
Published: April 2010

Objectives: To assess whether migraine patients display a chronic nitric oxide synthase (NOS) hyperactivity by comparing the nitric oxide (NO) production before and following a loading dose of L-arginine between migraine patients (interictally) and matched healthy control subjects. In addition, we evaluated whether a loading dose of L-arginine triggers an acute migraine headache in migraineurs.

Subjects and methods: Twenty healthy subjects and 20 migraine patients participated in a 2-period, randomised, double-blind, placebo-controlled study. Each subject received a 30-min infusion, by peripheral vein, of 30 g L-arginine hydrochloride or placebo (i.e. an equal volume of 0.9% saline solution). Meanwhile, biomarkers associated with the L-arginine–NO pathway (i.e. exhaled NO/nasal NO), plasma citrulline and urinary excretion of nitrite/nitrate and cGMP were assessed before and for 6 h following the start of the infusion.

Results: At baseline, exhaled NO and nasal NO were higher in migraineurs compared to healthy subjects (mean ± 95% confidence interval): 15.9 (8.8, 23.0) parts per billion (ppb) versus 10.8 (7.0, 14.5) ppb for exhaled NO ( P = 0.04) and 76.3 (61.2, 91.4) versus 61.6 (51.2, 72.0) ppb for nasal NO ( P = 0.03), respectively. The AUC0–6in ppb for exhaled NO and nasal NO following L-arginine or saline infusion did not differ between both groups. The increase in L-citrulline, following L-arginine infusion, was smaller in migraine patients (15 (13, 18) µmol/l) compared to healthy volunteers (19 (16, 23) µmol/l; P = 0.046). In healthy subjects, both nitrate and cGMP excretion were higher following L-arginine compared to placebo infusion: 132.63 (100.24, 165.02) versus 92.07 (66.33, 117.82) µmol/mmol creatinine for nitrate ( P = 0.014) and 50.53 (42.19, 58.87) versus 39.64 (33.94, 45.34) nmol/mmol creatinine for cGMP ( P = 0.0003), respectively. In migraineurs, excretion of these biomarkers was comparable following L-arginine or saline infusion.

Conclusions: The results of the present study do not support the idea of a generalised increase in NO synthase activity in migraine patients outside of a migraine attack. The smaller increase in plasma L-citrulline, urinary nitrate and cGMP excretion following L-arginine infusion in migraine patients might indicate dysfunction of endothelial NO synthase.
Reversible cerebral vasoconstriction syndrome in two patients with a carotid glomus tumour
Authors: Verillaud Benjamin , Ducros Anne , Massiou Hélène , Huy Patrice Tran Ba , Bousser Marie-Germaine , Herman Philippe
Published: April 2010

We report two patients with reversible cerebral vasoconstriction syndrome (RCVS) and carotid glomus tumour. The first patient presented with multiple thunderclap headaches. Cervical and cerebral magnetic resonance imaging showed diffuse cerebral vasoconstriction on magnetic resonance angiogram (MRA) and a carotid glomus tumour. The second patient presented with a cervical mass and was diagnosed with a non-secreting paraganglioma of the carotid body. Surgery with pre-operative angiography was followed by thunderclap headaches and MRA showed segmental cerebral vasoconstriction. Both patients were treated with nimodipine and headaches stopped. Both had normal cerebral arteries on the control MRA at 3 months. These two cases suggest that a paraganglioma may increase the susceptibility to develop RCVS. As a consequence, patients with RCVS should be investigated for a carotid glomus tumour, and patients with paraganglioma reporting severe headaches should have a cerebral MRA in order to rule out cerebral vasoconstriction.
Episodic and chronic migraineurs are hypersensitive to thermal stimuli between migraine attacks
Authors: Schwedt Todd J , Krauss Melissa J , Frey Karen , Gereau Robert W
Published: April 2010

Objective: To determine if migraineurs have evidence of interictal cutaneous sensitisation.

Subjects and methods: Thermal and mechanical pain thresholds in 20 episodic migraineurs, 20 chronic migraineurs, and 20 non-migraine control subjects were compared. Quantitative sensory testing was conducted when subjects had been migraine-free for at least 48 h. Heat, cold and mechanical pain thresholds, and heat and cold pain tolerance thresholds were measured.

Results: Thermal pain thresholds and thermal pain tolerance thresholds differed significantly by headache group ( P = 0.001). During the interictal period, episodic and chronic migraineurs were more sensitive to thermal stimulation than non-migraine controls.

Conclusions: Interictal sensitisation may predispose the migraineur to development of headaches, may be a marker of migraine activity, and a target for treatment.
Rapid Isolation of Human Stem Cells (Connective Tissue Progenitor Cells) From the Proximal Humerus During Arthroscopic Rotator Cuff Surgery
Authors: Mazzocca Augustus D. , McCarthy Mary Beth R. , Chowaniec David M. , Cote Mark P. , Arciero Robert A. , Drissi Hicham
Published: April 2010

Background: Bone-to-tendon healing in the shoulder can be unpredictable. Biologic augmentation, through the implementation of adult mesenchymal stem cells, may improve this healing process.

Purpose: The purpose of this study was to (1) arthroscopically obtain bone marrow aspirates from the proximal humerus during rotator cuff repair, (2) purify and concentrate the connective tissue progenitor cells (CTPs) in the operating room efficiently, and (3)confirm these are stem cells through their ability to differentiate into bone cells. We hypothesize that CTPs can be quickly and efficiently isolated from bone marrow during arthroscopic surgery and that these cells are capable of osteogenesis.

Study Design: Cohort study; Level of evidence, 3; and Descriptive laboratory study.

Methods: Bone marrow aspirates were harvested through the anchor tunnel of the humeral head during arthroscopic rotator cuff repair in 23 patients. Twenty-three matched controls were selected from a clinical registry to evaluate for increased incidence of complication. Connective tissue progenitor cells were isolated using 2 accepted methods and compared with a novel, rapid method designed for use in the operating room. Osteogenic potential was assessed by cytochemical and molecular analysis.

Results: Reverse transcription polymerase chain reaction analysis and cellular staining confirmed the osteogenic potential of these CTPs. There was no statistical significant difference in the Single Assessment Numeric Evaluation score (aspirate, 86.3 ± 10.5; control, 83.6 ± 15.1; P = .54), range of motion measures (postoperative external rotation: aspirate, 65.0° ± 20.4°; control, 62.5° ± 17.1°; P = .67; postoperative forward elevation: aspirate, 163.0° ± 30.6°; control, 145.7° ± 41.4°; P = .12), or postoperative strength measures between groups (median, 5; range, 4-5 in the aspirate group compared with median, 5; range, 4-5 in the control group; P > .05).

Conclusion: Connective tissue progenitor cells can be safely and efficiently aspirated from the proximal humerus using the anchor tunnel created during arthroscopic rotator cuff surgery. These cells may play an important role in cell-based therapies involving rotator cuff repair.

Clinical Relevance: We have established a reliable, reproducible protocol for isolating CTPs in the operating room. These cells may have the potential to enhance the healing process after rotator cuff repair.
Evaluation of Telehealth for Preclinic Assessment and Follow-Up in an Interprofessional Rural and Remote Memory Clinic
Authors: Morgan Debra G. , Crossley Margaret , Kirk Andrew , McBain Lesley , Stewart Norma J. , D’Arcy Carl , Forbes Dorothy , Harder Sheri , Bello-Haas Vanina Dal , Basran Jenny
Published: April 2010

Using data from a sample of 169 patients, this study evaluates the acceptability and feasibility of telehealth videoconferencing for preclinic assessment and follow-up in an interprofessional memory clinic for rural and remote seniors. Patients and caregivers are seen via telehealth prior to the in-person clinic and followed up at 6 weeks, 12 weeks, 6 months, 1 year, and yearly. Patients are randomly assigned to in-person (standard care) or telehealth for the first follow-up, then alternating between the two modes of treatment, prior to 1-year follow-up. On average, telehealth appointments reduce participants’ travel by 426 km per round trip. Findings show that telehealth coordinators rated 85% of patients and 92% of caregivers as comfortable or very comfortable during telehealth. Satisfaction scales completed by patient–caregiver dyads show high satisfaction with telehealth. Follow-up questionnaires reveal similar satisfaction with telehealth and in-person appointments, but telehealth is rated as significantly more convenient. Predictors of discontinuing follow-up are greater distance to telehealth, old-age patient, lower telehealth satisfaction, and lower caregiver burden.
Life-cycle assessment (EASEWASTE) of two municipal solid waste incineration technologies in China
Authors: Dezhen Chen  , Christensen Thomas H.
Published: April 2010

The environmental profile of two municipal solid waste incineration (MSWI) technologies with semi-dry flue gas cleaning, namely grated firing incinerators (GFI) and fluidised bed incinerators (FBI) that are commonly used in China were evaluated and compared by life-cycle assessment (LCA) using the EASEWASTE model. All emissions of key pollutants as well as energy, resource and material inputs and outputs associated with the two MSWI technologies were determined and the corresponding environmental impact potentials were modelled. Incineration of MSW with a lower heating value (LHV) around 4.5 MJ kg—1 demands that auxiliary fuel is used, and both GFI and FBI caused environmental loads by contributing with environmental impact potentials in most categories except for some saving in global warming (GW100) and hazardous waste (HW). Coal combustion in FBI is a main contributor to the environmental impact potentials and thus should always be limited to a minimum. Auxiliary fuels can be avoided when the LHV of MSW is higher than 5—6 MJ kg— 1. For all scenarios, GFI saves more global warming potentials than FBI due to its higher net power generation from combustion of MSW itself. Leachate from the bunker could be sprayed into the furnace for evaporation under high temperature, as an alternative to waste-water treatment, without major changes in the environmental profile of the incinerator. The presented evaluations may contribute to a more balanced environmental assessment of the two incineration technologies with respect to incineration of MSW with low heating values as often found in Asia and China.
The Lived Experience of Feeling Misunderstood
Authors: Condon Barbara Backer
Published: April 2010

The purpose of this study was to uncover the structure of the lived experience of feeling misunderstood. Parse’s phenomenological-hermeneutic research method was used to answer the research question: What is the structure of the lived experience of feeling misunderstood? Extraction-synthesis revealed four core concepts. The structure is the lived experience of feeling misunderstood is disheartening insignificance surfacing with discordant affiliations, as resignation with resiliency emerges with inventive endeavors. Implications for nursing research and practice are presented.
Patient Weight as a Predictor of Pain Response to Morphine in the Emergency Department
Authors: Patanwala Asad E. , Biggs Adam D. , Erstad Brian L.
Published: April 2010

Study Objectives: There is little evidence that patient weight is associated with pain response to morphine in the emergency department (ED). The primary outcome of this study is to identify demographic variables including patient weight that are associated with an adequate pain reduction after the first dose of morphine. Methods: A retrospective chart review of all patients with severe nontraumatic abdominal pain receiving intravenous morphine was conducted in our ED over a 3-month time period. Pain score, using an 11-point verbal numerical pain scale (0-10), was measured before and after each dose of morphine. Adequate response was defined as a ≥ 4-point reduction from baseline pain score. Results: A total of 105 patients were included in the analysis. Univariate logistic regression analyses stratified by dose (2 or 4 mg) showed that patient weight was not predictive of adequate pain response after the first dose of morphine (2 mg: odds ratio = 1; 95% confidence interval 0.97-1.03; P = .88; 4 mg: odds ratio = 1; 95% confidence interval 0.97-1.03; P = .86). Conclusions: Patient weight may not predict pain response to morphine in the ED. Dosing strategies based on patient weight may not be necessary in this patient population.
Effect of climatic and palaeoenvironmental changes on the occurrence of Holocene bats in the Swiss Alps
Authors: Blant Michel , Moretti Marco , Tinner Willy
Published: April 2010

A large-scale palaeozoological study compared 4514C-dated bat remains from the southern and northern Swiss Alps with palaeovegetational and palaeoclimatic data. Four thermophilous (warm-demanding) and four psychrophilous (cold-tolerant) bat species, mainly forest dwellers, were selected for the study. Myotis blythii is the oldest bat species recorded in the Alps, i.e. on the southern side, going back to the early Holocene at 10 500 cal. BP. Our study showed that thermophilous species (e.g. Myotis bechsteinii and Rhinolophus hipposideros) were most abundant during the Holocene climatic optimum in Central Europe (10 000—4000 cal. BP), when warm-demanding mixed forests were dominant. Psychrophilous species such as Myotis brandtii also occurred during the climatic optimum, but most of the samples fall into the onset of the late Holocene (Sub-Atlantic period), when summer temperatures were already declining. These species declined in the southern Alps after 4000 cal. BP, when fire was intensively used by humans to convert portions of the forest into open land. This fire practice modified forest species composition and structure, with effects on forest-dwelling bat communities. We conclude that during the early and mid Holocene bat community compositions mainly depended on climate and related vegetation and forest structure dynamics. With increasing land use during the mid and late Holocene, anthropogenic changes of forest composition and creation of open habitats increasingly co-determined bat-population dynamics in the Alps. These Swiss findings are in agreement with previous results from eastern Central Europe.
Ashtead Common, the evolution of a cultural landscape: A spatially precise vegetation record for the last 2000 years from southeast England
Authors: Waller Martyn
Published: April 2010

The results of palaeoecological (pollen and fungal spores) investigations of an abandoned clay pit on Ashtead Common, Surrey are presented and compared with archaeological and documentary evidence. The pit lies adjacent to a Roman industrial complex, with early Saxon activity recorded nearby. Prior to the early twentieth century AD the Common was managed as wood-pasture and it has a high nature conservation designation as a result of c. 2000 veteran pollarded oak trees which remain from this phase. The pit provides a record of landscape history from the Roman ( c. cal. AD 150) to the modern ( c. AD 1850) era which, in terms of spatial and temporal resolution, is unrivalled in southeast England. From the late Roman into the middle Saxon period the palaeoecological data are consistent with archaeological evidence for the continuity of settlement and land use. Subtle changes in woodland cover, probably reflecting changes in the importance of grazing against the exploitation of wood, are evident up to c. cal. AD 1200. Thereafter grazing pressure on the Common appears to have increased and the resulting shortage of underwood is likely to have led eventually (cal. AD 1490—1680) to the adoption of pollarding. Changes in depositional environment are shown to have a major impact on the fungal spore record. In general terms the stratigraphic data from the Ashtead Common pit accord well with archaeological/documentary evidence and demonstrate the utility of studies which use a combination of sources to reconstruct vegetation change in the historic era.
The role of heart-type fatty acid-binding protein in the evaluation of carbon monoxide poisoning in rats
Authors: Yardan Turker , Meric Murat , Bozkurt Ayhan , Bilge Sirri , Bas Duygu Belkis , Bedir Abdulkerim , Ozdemir Tulay , Baydin Ahmet
Published: April 2010

Acute carbon monoxide (CO) poisoning can cause early and persistent damages in tissues sensitive to hypoxia. This study investigated serum heart-type fatty acid-binding protein (H-FABP) levels as a biomarker of acute CO poisoning in rats. The rats were exposed to a mixture of either 3000 (group A) or 5000 (group B) parts per million (ppm) CO in air, or to ambient air (group C, control group). Blood samples were taken just before, immediately after and 6 hours after the exposure, and serum H-FABP and troponin-I levels were measured. The consciousness level was evaluated just after the exposure. The survival rate was monitored for 7 days. Serum H-FABP levels increased just after the CO exposure in both groups A and B. Additionally, H-FABP level was higher in group B than in group A, immediately after the exposure. However, serum troponin-I levels only increased at 6 hours after the CO exposure in groups A and B. Consciousness and survival rates in group B were lower than that in group A. Our results suggest that H-FABP might have potential to be an early and quantitative parameter of clinical severity and prognosis in CO poisoning.
Effect of saccharin on albino rats’ blood indices and the therapeutic action of vitamins C and E
Authors: Abdelaziz Ismael , Ashour Abd El Rahiem A
Published: April 2010

The present work aimed to study some blood indices of rats as affected by saccharin and the therapeutic action of vitamins C and E. The used adult female Rattus norvegicus albino rats in the present study were weighing 100—120 g. Administration of saccharin at a dose of 35 mg kg—1 body weight (b.wt.) day—1 for 35 days significantly decreased serum glucose, triglycerides, cholesterol, total protein and albumin values. These decrements were by 20.16%, 22.76%, 44.92%, 20.16% and 40.44%, respectively, compared to control level (p value < 0.01). But it increased levels of kidney function indices. The effect of saccharin was more pronounced on creatinine. Activities of Alanine aminotranferease (ALT), aspartate aminotransferase (AST) and Alkaline phosphatase (ALP) increased significantly following saccharin treatment to rats. Concerning hematoligical parameters, the more obvious changes were observed in the increment of white blood cell (WBC), mean corpuscular volume (MCV) and platelets (PLT) and the decrease in hematocrit, hemoglobin (Hb) and red blood cells (RBCs) count in response to the administration of saccharin. In general, vitamin C or E (150 mg kg—1 b.wt. day—1 for 35 days) was able to reduce the effects of saccharin intake. Both vitamins, however, generally have beneficial effects in reducing the changes in the studied parameters.
Disease activity and damage accrual during the early disease course in a multinational inception cohort of patients with systemic lupus erythematosus
Authors: Nossent J. , Kiss E. , Rozman B. , Pokorny G. , Vlachoyiannopoulos P. , Olesinska M. , Marchesoni A. , Mosca M. , Påi S. , Manger K. , Schneider M. , Nielsen H. , van Vollenhoven R. , Swaak T.
Published: April 2010

An inception cohort of patients with systemic lupus erythematosus from 14 European centres was followed for up to 5 years in order to describe the current early disease course. At inclusion patients (n = 200, 89% female, mean age 35 years, 97% Caucasian, mean SLEDAI 12.2) fulfilled a mean of 6.5 ACR classification criteria. The most prevalent criteria were antinuclear Ab presence (97%) followed by anti-dsDNA Ab (74%), arthritis (69%), leukocytopenia (54%) and malar rash (53%), antiphospholipid Ab (48%) and anti-synovial membrane Ab (21.6%). Clinical signs of lupus nephritis (LN) were present in 39% with biopsy-confirmed LN seen in 25%. Frequent additional findings were hypocomplementaemia (54%), anti-SSA Ab (49%), alopecia (26%) and Raynaud’s phenomenon (31%). There were few regional differences in disease presentation and management. One and 5-year survival rates were 99% and 97% respectively. During the mean follow-up of 4.1 years 25% entered a state of early disease quiescence by global physician assessment, but the overall risk of subsequent flare was 60%. Maximum SLEDAI scores decreased over time, but 45% of patients accrued damage (SDI ≥1) for which baseline presence of proteinuria and persistent disease activity were independent predictors. The results indicate minor differences in SLE presentation and treatment within various regions of Europe and a high diagnostic reliance on anti-dsDNA Ab. Despite early reductions in disease activity and improved mortality, the risk for disease flare and damage development is, however, still substantial, especially in patients not entering an early remission.
Undergraduate International Medical Electives: Some Ethical and Pedagogical Considerations
Authors: Hanson Lori , Harms Sheila , Plamondon Katrina
Published: April 2010

The authors argue that attempts to establish more placements to meet the growing demands of undergraduate medical students in North America for international experiences may be outweighing critical reflection on the ethical issues, curricular content, and pedagogical strategies necessary to support equitable engagements with countries of the Global South. On the basis of a critical analysis of literature on international medical electives and experiences (IMEs), the article explores trends in IMEs and exposes several prominent issues, including paradoxes in underlying motivations, missing or ad hoc curricula and pedagogical approaches in IMEs, and ethical challenges that frequently arise. By engaging perspectives from critical educational theory, the authors suggest that IMEs as currently conceived are potentially ripe sites for the reproduction of colonialist ideas of North—South relationships. The authors conclude that IMEs will do little to address historically and politically rooted global health inequities unless critical consciousness is raised through improved global health curricula and appropriate pedagogical strategies.
Dynamic Optimization for Vibration Systems Including Hydraulic Engine Mounts
Authors: Jie Wu  , Shangguan Wen-Bin
Published: April 2010

In this paper we present a calculation method in the time domain for vibration systems including hydraulic engine mounts (HEMs) to evaluate the vibrations of a body that is a sprung mass in bounce and roll modes. A fractional derivative model is used to describe the frequency-dependent dynamic properties of a HEM. A two degree-of-freedom vibration system with two mounts is considered to demonstrate the use of the method. An optimization method is proposed to suppress body vibrations in the two modes. Optimization results show that body vibrations can be effectively suppressed using the HEMs designed on the basis of the optimization method.
Impact Response of Torsionally Coupled Base-isolated Structures
Authors: Matsagar V.A. , Jangid R.S.
Published: April 2010

The seismic response of a single-story asymmetric structure supported on various base isolation systems during impact with adjacent structures is investigated. Eccentricities arising due to elastic forces in the columns at the top-deck and the restoring forces in the isolation systems at the base-raft are considered. The adjacent structures (i.e. retaining walls or entry bridges) surrounding the base-isolated structure on all four sides are modeled in the form of springs and dashpots. The coupled differential equations of motion for the isolated system are derived and solved in incremental form using Newmark’s method to obtain the seismic response with and without impact. The variation of superstructure acceleration and isolation level displacement during impact upon the adjacent structures under the action of real earthquakes are computed to study the behavior of torsionally coupled structures and compare the performance of various isolation systems. The torsional impact response of isolated structures is studied under the variation of important system parameters such as the sizes of gaps, the stiffness of adjacent structures, superstructure flexibility and different eccentricities in the base-isolated structure. It is concluded that the lateral-torsional response of the base-isolated structure is adversely affected when impact takes place with the adjacent structures. The superstructure acceleration increases and the base-raft displacement decreases due to impact with the adjacent structures; nevertheless, the isolation remains effective as compared to the nonisolated case. Further, it is also observed that superstructure acceleration increases with increase of the isolation gap distances up to a certain value and then the acceleration decreases with its further increase. The effects of impact are found to be severe for systems with flexible superstructure, stiffer adjacent structures and increased eccentricities.
Exploring the Impact of Race on Mental Health Service Utilization Among African Americans and Whites With Severe Mental Illness
Authors: DeCoux Hampton Michelle , Chafetz Linda , White Mary C.
Published: April 2010

BACKGROUND: Disparities among African Americans and Whites with severe mental illness have been identified in numerous studies. Yet it remains unknown if disparities are associated with race or other vulnerabilities common to this population. OBJECTIVES: This study used the Behavioral Model for Vulnerable Populations to examine mental health service utilization among 155 African Americans and Whites with severe mental illness for 12 months after discharge from a residential crisis program. DESIGN: This cross-sectional study was a secondary analysis of data from a randomized trial. RESULTS: Race did not emerge as a significant predictor of mental health service utilization. Factors associated with frequency of service use were diagnosis, age, drug use, gender, health benefit status, and enrollment in an outpatient mental health program. CONCLUSION: It is possible that the geographic location of the study, equal access to services, and equal rates of substance use between racial groups explain the lack of racial differences found in this sample.
Rapid Response Team for Behavioral Emergencies
Authors: Loucks Jeannine , Rutledge Dana N. , Hatch Beverly , Morrison Victoria
Published: April 2010

Behaviors of patients with psychiatric illness who are hospitalized on nonbehavioral health units can be difficult to address by staff members. Instituting a rapid response team to proactively de-escalate potential volatile situations on nonpsychiatric units in a hospital allows earlier treatment of behavioral issues with these patients. The behavioral emergency response team (BERT) consists of staff members (registered nurses, social workers) from behavioral health services who have experience in caring for patients with acute psychiatric disorders as well as competence in management of assaultive behavior. BERT services were trialed on a medical pulmonary unit; gradual housewide implementation occurred over 2 years. Tools developed for BERT include an activation algorithm, educational cue cards for staff, and a staff survey. Results of a performance improvement survey reveal that staff nurses have had positive experiences with BERT but that many nurses are still not comfortable caring for psychiatric patients on their units.
Role of Hyperparathyroidism in the Management of Depression and Anxiety
Authors: Allen Kathleen S. , Bostwick Jolene R.
Published: April 2010

A thorough workup of patients who present with depression and anxiety is imperative to treat underlying conditions in order to potentially decrease psychiatric symptoms. This case describes the hospital course of a patient previously diagnosed with depression and anxiety who experienced an exacerbation of symptoms that may have been related to hyperparathyroidism.
Self-efficacy is associated with walking ability in persons with diabetes mellitus and peripheral arterial disease
Authors: Collins Tracie C , Lunos Scott , Ahluwalia Jasjit S
Published: April 2010

Self-efficacy is a known predictor for behavior change. Little is known about the association of self-efficacy with walking ability in individuals with diabetes mellitus and peripheral arterial disease (PAD). The objective of this study was to determine the association of self-efficacy with walking ability in individuals with diabetes mellitus and PAD. In this cross-sectional study, baseline data were analyzed from individuals with diabetes mellitus type 1 or 2 and PAD who were enrolled in a walking intervention clinical trial. As part of the baseline assessment, individuals completed questionnaires to ascertain self-efficacy and co-existing illnesses. In addition, participants completed a treadmill walking test and a 6-minute walking test. A total of 145 individuals were enrolled (mean age 66.5 ± 10.1 years) with diabetes mellitus and PAD; 45 (31%) were women. The mean ankle—bracial index was 0.70 (range − 0.18—2.20) and the mean glycosylated hemoglobin value was 7.1 (SD 1.2). The mean distance walked, as per the treadmill walking test, was 418 meters (SD 258) and the mean distance walked, as per the 6-minute walking test, was 272 meters (SD 74). As measured by the treadmill walking test and the 6-minute walking test, self-efficacy was associated with treadmill walking distance, coefficient 33.0 (95% CI 11.0, 55.1; p = 0.0036), and the 6-minute walking test, coefficient 10.4 (95% CI 3.0, 17.7; p = 0.0061), after adjusting for comorbidities, social habits, and disease severity. In conclusion, self-efficacy, a psychosocial mediator for behavior change, was significantly associated with walking ability in individuals with diabetes mellitus and PAD. Future studies should determine the benefits of targeting self-efficacy to improve adherence to walking therapy in patients with PAD.
Performance Gains from Speech-enhanced Simulation in Military Flying Training
Authors: Bell Benjamin , Billington Stacie , Bennett Winston , Billington Ian , Ryder Joan
Published: April 2010

Flight simulation is a proven technique for training technical and procedural skills, but team skills present needs that remain unmet by simulator technology. Communication and coordination, two skills representative of this gap, are typically incorporated into simulation via human role players, a practice that entails cost, introduces variation, and can compromise availability of training. In this article we explore the use of speech-interactive synthetic teammates to bring team skills into simulation-based training. We report on a US Air Force study that led to the development of a desktop air traffic pattern simulation for practicing radio communications, and present findings from a study conducted with US Air Force student pilots who employed this system during part of their pilot training. The work reported here addresses two questions. First, can contemporary desktop simulation augmented with intelligent agents and voice recognition provide training gains in communications performance among student pilots? Second, will users accept this approach?
Myxedema Coma Precipitated by Diabetic Ketoacidosis
Authors: Kelekar Gauri , Milanesi Anna , Yu Run
Published: April 2010

Objective:

To describe a rare case of myxedema coma with atypical presentation precipitated by diabetic ketoacidosis.

Methods:

The authors present a case report, including the detailed clinical and laboratory data, and review other significant reports available in the literature.

Results:

A 62-year-old woman with recent history of radioactive iodine therapy for Graves’ disease was admitted to the hospital for altered mental status and hyperglycemia. After treatment for diabetic ketoacidosis with intravenous fluid and insulin, hyperglycemia and ketonuria corrected, but her mental status remained profoundly compromised. Clinical conditions rapidly improved after initiation of treatment for myxedema coma with intravenous levothyroxine.

Conclusion:

This is a rare case of myxedema coma precipitated by diabetic ketoacidosis. Moreover, our case suggests that diabetic ketoacidosis can mask the typical clinical and laboratory features of myxedema coma, making the final diagnosis very challenging. Early recognition of an atypical presentation of myxedema coma is important to avoid the potential fatal outcome.
Implementation of a High-Dose Interleukin-2 Immunostimulation Biotherapy Program
Authors: Yost C. Spencer , Daud Adil , Gropper Michael A.
Published: April 2010

Interleukin-2 (IL-2) is a cytokine that produces an in vivo immunostimulating effect when given systemically. This action may arise from stimulating the growth and expansion of cytotoxic T cells that in turn activate natural killer cells to attack tumors such as malignant melanoma and renal cell carcinoma. Therefore, administration of high-dose IL-2 can invoke an antitumor response in some patients. However, high-dose IL-2 induces severe and sometimes life-threatening toxicity, including vascular leak syndrome, hypotension, fever, and end-organ damage. Renal, hepatic, pulmonary, cardiac, and neurologic side effects have been described. Patients receiving IL-2 therefore require close monitoring to detect and treat life-threatening complications arising from treatment. The authors describe the steps taken to begin an IL-2 biotherapy program in a small ICU at a regional comprehensive cancer center. The addition of “elective” IL-2 admissions to the ICU has had a beneficial effect on stabilizing the daily census. In addition, it has brought a new cohort of patients who are highly appreciative of the care they receive and provides the nursing staff a new opportunity to develop expertise with cancer biotherapy.
Interleukin-2 Infusions and Systemic Inflammatory Response Syndrome
Authors: Henderson-MacLennan Leon
Published: April 2010

Warren Roston, MD, is a board-certified pulmonologist in Los Angeles. He is a voluntary staff member at a major teaching hospital and practices inpatient medicine with a mixed hospitalist- and intensive-care focus. In this profile, he was interviewed regarding his experience as a patient who experienced systemic inflammatory response syndrome in the context of treatment for melanoma with interleukin-2.
A Primer
Authors: Hackner Dani
Published: April 2010

In this 2-part article, we hope to join the reader in the broader discussion over ICU staffing. From the perspective of the clinician, we provide references to central concepts and landmark studies identifying organizational elements linked to patient outcomes. From the perspective of the unit management, we provide access to the literature on clinician interaction and organizational ethics. From the human resources (HR) literature, we provide relevant principles, standard practices, and concerns that should alert clinicians to seek HR and risk management consultation. In Part 1, we introduce many of the concepts relevant to staffing, hiring, and orienting teams toward performance. In Part 2, we explore management and business models as well as unit operations in relation to staff interests and concerns. The primer encourages managers and directors as well as clinicians and support staff to take a mindful stroll through each others’ concerns and published literature.
Review: Diagnostic Modalities for Diseased Articular Cartilage-From Defect to Degeneration: A Review
Authors: Bekkers J.E.J. , Creemers L.B. , Dhert W.J.A. , Saris D.B.F.
Published: April 2010

The progression of cartilage matrix damage to generalized degeneration is associated with specific pathophysiological and clinical aspects. Reliable detection of stage-related characteristics of cartilage disease serves both a therapeutic and prognostic goal. Over the past years, several (pre)clinical diagnostic modalities for cartilage pathologies have been advocated. Each modality focuses on different aspects of the disease. Early diagnosis, before irreversible damage has occurred, opens up the possibility for better treatment and improves the patients’ prognosis. This article gives an overview of the diagnostic modalities available for monitoring cartilage pathology and focuses on reliability, clinical value, current status, and possible applications.
An investigation of dynamic recrystallisation on Cu–Sn bronze using 3D EBSD
Authors: Gholinia A. , Brough I. , Humphreys J. , McDonald D. , Bate P.
Published: April 2010

A focused ion beam and electron backscatter diffraction were used to investigate the three-dimensional microstructure of small dynamically recrystallised grains in a deformed Cu–Sn alloy and to determine their orientation relationships. It was found that many of the grains, which form as thin sheets at the prior boundaries, are twin related. It is concluded that dynamical recrystallisation usually starts in regions where plastic deformation has resulted in significant lattice rotations beside the grain boundaries. Once such a new grain has formed, dynamic recrystallisation is propagated by successive twinning from the new grain, along the prior grain boundary, resulting in families of several hundred twin related dynamically recrystallised grains.
Sensitive and selective detection of free FXIII activation peptide: a potential marker of acute thrombotic events
Authors: Ortner Elisabeth , Schroeder Verena , Walser Reto , Zerbe Oliver , Kohler Hans P.
Published: April 2010

Coagulation factor XIII (FXIII) stabilizes fibrin fibers and is therefore a major player in the maintenance of hemostasis. FXIII is activated by thrombin resulting in cleavage and release of the FXIII activation peptide (AP-FXIII). The objective of this study was to characterize the released AP-FXIII and determine specific features that may be used for its specific detection. We analyzed the structure of bound AP-FXIII within the FXIII A-subunit and interactions of AP-FXIII by hydrogen bonds with both FXIII A-subunit monomers. We optimized our previously developed AP-FXIII ELISA by using 2 monoclonal antibodies. We determined high binding affinities between the antibodies and free AP-FXIII and demonstrated specific binding by epitope mapping analyses with surface plasmon resonance and enzyme-linked immunosorbent assay. Because the structure of free AP-FXIII had been characterized so far by molecular modeling only, we performed structural analysis by nuclear magnetic resonance. Recombinant AP-FXIII was largely flexible both in plasma and water, differing significantly from the rigid structure in the bound state. We suggest that the recognized epitope is either occluded in the noncleaved form or possesses a structure that does not allow binding to the antibodies. On the basis of our findings, we propose AP-FXIII as a possible new marker for acute thrombotic events.
A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma
Authors: Görgün Güllü , Calabrese Elisabetta , Hideshima Teru , Ecsedy Jeffrey , Perrone Giulia , Mani Mala , Ikeda Hiroshi , Bianchi Giada , Hu Yiguo , Cirstea Diana , Santo Loredana , Tai Yu-Tzu , Nahar Sabikun , Zheng Mei , Bandi Madhavi , Carrasco Ruben D. , Raje Noopur , Munshi Nikhil , Richardson Paul , Anderson Kenneth C.
Published: April 2010

Aurora-A is a mitotic kinase that regulates mitotic spindle formation and segregation. In multiple myeloma (MM), high Aurora-A gene expression has been correlated with centrosome amplification and proliferation; thus, inhibition of Aurora-A in MM may prove to be therapeutically beneficial. Here we assess the in vitro and in vivo anti-MM activity of MLN8237, a small-molecule Aurora-A kinase inhibitor. Treatment of cultured MM cells with MLN8237 results in mitotic spindle abnormalities, mitotic accumulation, as well as inhibition of cell proliferation through apoptosis and senescence. In addition, MLN8237 up-regulates p53 and tumor suppressor genes p21 and p27. Combining MLN8237 with dexamethasone, doxorubicin, or bortezomib induces synergistic/additive anti-MM activity in vitro. In vivo anti-MM activity of MLN8237 was confirmed using a xenograft-murine model of human-MM. Tumor burden was significantly reduced (P = .007) and overall survival was significantly increased (P < .005) in animals treated with 30 mg/kg MLN8237 for 21 days. Induction of apoptosis and cell death by MLN8237 were confirmed in tumor cells excised from treated animals by TdT-mediated dUTP nick end labeling assay. MLN8237 is currently in phase 1 and phase 2 clinical trials in patients with advanced malignancies, and our preclinical results suggest that MLN8237 may be a promising novel targeted therapy in MM.
Hematopoietic activity of human short-term repopulating cells in mobilized peripheral blood cell transplants is restricted to the first 5 months after transplantation
Authors: Zavidij Oksana , Ball Claudia R. , Herbst Friederike , Fessler Sylvia , Schmidt Manfred , von Kalle Christof , Glimm Hanno
Published: April 2010

Kinetics of hematopoietic recovery driven by different types of human stem and progenitor cells after transplantation are not fully understood. Short-term repopulating cells (STRCs) dominate early hematopoiesis after transplantation. STRCs are highly enriched in adult mobilized peripheral blood compared with cord blood, but the length of their contribution to hematopoiesis remains unclear. To understand posttransplantation durability and lineage contribution of STRCs, we compared repopulation kinetics of mobilized peripheral blood (high STRC content) with cord blood transplants (low STRC content) in long-lived NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (IL2RG−/−) mice. This comparison demonstrates that quantitative contribution of human STRCs to hematopoiesis is restricted to the first 5 months after transplantation. The ratio of STRCs to long-term repopulating cells dramatically changes during ontogeny. This model enables to precisely determine early and late engraftment kinetics of defined human repopulating cell types and to preclinically assess the engraftment kinetics of engineered stem cell transplants.
Significantly improved precision of cell migration analysis in time-lapse video microscopy through use of a fully automated tracking system
Authors: Huth Johannes , Buchholz Malte , Kraus Johann M , Schmucker Martin , von Wichert Götz , Krndija Denis , Seufferlein Thomas , Gress Thomas M , Kestler Hans A
Published: April 2010

Background

Cell motility is a critical parameter in many physiological as well as pathophysiological processes. In time-lapse video microscopy, manual cell tracking remains the most common method of analyzing migratory behavior of cell populations. In addition to being labor-intensive, this method is susceptible to user-dependent errors regarding the selection of "representative" subsets of cells and manual determination of precise cell positions.

Results

We have quantitatively analyzed these error sources, demonstrating that manual cell tracking of pancreatic cancer cells lead to mis-calculation of migration rates of up to 410%. In order to provide for objective measurements of cell migration rates, we have employed multi-target tracking technologies commonly used in radar applications to develop fully automated cell identification and tracking system suitable for high throughput screening of video sequences of unstained living cells.

Conclusion

We demonstrate that our automatic multi target tracking system identifies cell objects, follows individual cells and computes migration rates with high precision, clearly outperforming manual procedures.
Exocrine-to-endocrine differentiation is detectable only prior to birth in the uninjured mouse pancreas
Authors: Kopinke Daniel , Murtaugh L Charles
Published: April 2010

Background

Histological evidence suggests that insulin-producing beta (β)-cells arise in utero from duct-like structures of the fetal exocrine pancreas, and genetic lineage tracing studies indicate that they are maintained in the adult by self-renewal. These studies have not addressed the origin of the new β-cells that arise in large numbers shortly after birth, and contradictory lineage tracing results have been published regarding the differentiation potential of duct cells in this period. We established an independent approach to address this question directly.

Results

We generated mice in which duct and acinar cells, comprising the exocrine pancreas, can be genetically marked by virtue of their expressing the mucin gene Muc1. Using these mice, we performed time-specific lineage tracing to determine if these cells undergo endocrine transdifferentiation in vivo. We find that Muc1+ cells do give rise to β-cells and other islet cells in utero, providing formal proof that mature islets arise from embryonic duct structures. From birth onwards, Muc1 lineage-labeled cells are confined to the exocrine compartment, with no detectable contribution to islet cells.

Conclusions

These results argue against a significant contribution by exocrine transdifferentiation to the normal postnatal expansion and maintenance of β-cell mass. Exocrine transdifferentiation has been proposed to occur during injury and regeneration, and our experimental model is suited to test this hypothesis in vivo.
Cerebrospinal fluid promotes survival and astroglial differentiation of adult human neural progenitor cells but inhibits proliferation and neuronal differentiation
Authors: Buddensiek Judith , Dressel Alexander , Kowalski Michael , Runge Uwe , Schroeder Henry , Hermann Andreas , Kirsch Matthias , Storch Alexander , Sabolek Michael
Published: April 2010

Background

Neural stem cells (NSCs) are a promising source for cell replacement therapies for neurological diseases. Growing evidence suggests an important role of cerebrospinal fluid (CSF) not only on neuroectodermal cells during brain development but also on the survival, proliferation and fate specification of NSCs in the adult brain. Existingin vitrostudies focused on embryonic cell lines and embryonic CSF. We therefore studied the effects of adult human leptomeningeal CSF on the behaviour of adult human NSCs (ahNSCs).

Results

Adult CSF increased the survival rate of adult human NSCs compared to standard serum free culture media during both stem cell maintenance and differentiation. The presence of CSF promoted differentiation of NSCs leading to a faster loss of their self-renewal capacity as it is measured by the proliferation markers Ki67 and BrdU and stronger cell extension outgrowth with longer and more cell extensions per cell. After differentiation in CSF, we found a larger number of GFAP+astroglial cells compared to differentiation in standard culture media and a lower number of β-tubulin III+neuronal cells.

Conclusions

Our data demonstrate that adult human leptomeningeal CSF creates a beneficial environment for the survival and differentiation of adult human NSCs. Adult CSF isin vitroa strong glial differentiation stimulus and leads to a rapid loss of stem cell potential.