bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cucurbitacin B, a novel in vivo potentiator of gemcitabine with low toxicity in the treatment of pancreatic cancer
Authors: Iwanski Gabriela B , Lee Dhong H , En‐Gal Shlomit , Doan Ngan B , Castor Brandon , Vogt Marco , Toh Melvin , Bokemeyer Carsten , Said Jonathan W , Thoennissen Nils H , Koeffler H Phillip 
Published: March 2010

Background and purpose:  Pancreatic cancer is a highly aggressive malignancy, and improvement in systemic therapy is necessary to treat this frequently encountered metastatic disease. The current targeted agents used in combination with gemcitabine improved objective response rates, but with little or no improvements in survival and also increased toxicities in pancreatic cancer patients. Recently, we showed that the triterpenoid cucurbitacin B inhibited tumour growth in pancreatic cancer cells by inhibition of the JAK/STAT pathway, and synergistically increased antiproliferative effects of gemcitabine in vitro.Experimental approach:  The anti‐tumour effects and toxicities of cucurbitacin B in combination with gemcitabine were tested against human pancreatic cancer cells in a murine xenograft model.Key results:  Combined therapy with cucurbitacin B and gemcitabine at relatively low doses (0.5 mg·kg−1 and 25 mg·kg−1 respectively) resulted in highly significant tumour growth inhibition of pancreatic cancer xenografts (up to 79%). Remarkably, this therapy was well tolerated by the animals, as shown by histology of visceral organs, analysis of serum chemistry, full blood counts and bone marrow colony numbers. Western blot analysis of the tumour samples of mice who received both cucurbitacin B and gemcitabine, revealed stronger inhibition of Bcl‐XL, Bcl‐2 and c‐myc, and higher activation of the caspase cascades, than mice treated with either agent alone.Conclusions and implications:  Combination of cucurbitacin B and gemcitabine had profound anti‐proliferative effects in vivo against xenografts of human pancreatic cancer cells, without any significant signs of toxicity. This promising combination should be examined in therapeutic trials of pancreatic cancer.
Kinetic analysis of novel mono‐ and multivalent VHH‐fragments and their application for molecular imaging of brain tumours
Authors: Iqbal U , Trojahn U , Albaghdadi H , Zhang J , O'Connor‐McCourt M , Stanimirovic D , Tomanek B , Sutherland G , Abulrob A 
Published: March 2010

Background and purpose:  The overexpression of epidermal growth factor receptor (EGFR) and its mutated variant EGFRvIII occurs in 50% of glioblastoma multiforme. We developed antibody fragments against EGFR/EGFRvIII for molecular imaging and/or therapeutic targeting applications.Experimental approach:  An anti–EGFR/EGFRvIII llama single‐domain antibody (EG2) and two higher valency format constructs, bivalent EG2‐hFc and pentavalent V2C‐EG2 sdAbs, were analysed in vitro for their binding affinities using surface plasmon resonance and cell binding studies, and in vivo using pharmacokinetic, biodistribution, optical imaging and fluorescent microscopy studies.Key results:  Kinetic binding analyses by surface plasmon resonance revealed intrinsic affinities of 55 nM and 97 nM for the monovalent EG2 to immobilized extracellular domains of EGFR and EGFRvIII, respectively, and a 10‐ to 600‐fold increases in apparent affinities for the multivalent binders, V2C‐EG2 and EG2‐hFc, respectively. In vivo pharmacokinetic and biodistribution studies in mice revealed plasma half‐lives for EG2, V2C‐EG2 and EG2‐hFc of 41 min, 80 min and 12.5 h, respectively, as well as a significantly higher retention of EG2‐hFc compared to the other two constructs in EGFR/EGFRvIII‐expressing orthotopic brain tumours, resulting in the highest signal in the tumour region in optical imaging studies. Time domain volumetric optical imaging fusion with high‐resolution micro‐computed tomography of microvascular brain network confirmed EG2‐hFc selective accumulation/retention in anatomically defined tumour regions.Conclusions:  Single domain antibodies can be optimized for molecular imaging applications by methods that improve their apparent affinity and prolong plasma half‐life and, at the same time, preserve their ability to penetrate tumour parenchyma.
Phytocannabinoids beyond theCannabisplant – do they exist?
Authors: Gertsch Jürg , Pertwee Roger G , Di Marzo Vincenzo 
Published: March 2010

It is intriguing that during human cultural evolution man has detected plant natural products that appear to target key protein receptors of important physiological systems rather selectively. Plants containing such secondary metabolites usually belong to unique chemotaxa, induce potent pharmacological effects and have typically been used for recreational and medicinal purposes or as poisons.Cannabis sativaL. has a long history as a medicinal plant and was fundamental in the discovery of the endocannabinoid system. The major psychoactiveCannabisconstituent Δ9‐tetrahydrocannabinol (Δ9‐THC) potently activates the G‐protein‐coupled cannabinoid receptor CB1and also modulates the cannabinoid receptor CB2. In the last few years, several other non‐cannabinoid plant constituents have been reported to bind to and functionally interact with CB receptors. Moreover, certain plant natural products, from bothCannabisand other plants, also target other proteins of the endocannabinoid system, such as hydrolytic enzymes that control endocannabinoid levels. In this commentary we summarize and critically discuss recent findings.This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visithttp://dx.doi.org/10.1111/j.1476‐5381.2010.00831.x
Favorable Glucose Tolerance and Lower Prevalence of Metabolic Syndrome in Offspring without Diabetes Mellitus of Nonagenarian Siblings: The Leiden Longevity Study
Authors: Rozing Maarten P. , Westendorp Rudi G. J. , de Craen Anton J. M. , Frölich Marijke , de Goeij Moniek C. M. , Heijmans Bastiaan T. , Beekman Marian , Wijsman Carolien A. , Mooijaart Simon P. , Blauw Gerard‐Jan , Slagboom P. Eline , van Heemst Diana ,   on behalf of the Leiden Longevity Study Group
Published: March 2010

OBJECTIVES: To explore measures of metabolic syndrome and glucose metabolism in families with exceptional longevity.DESIGN: Case–control study.SETTING: A university hospital in Leiden, the Netherlands.PARTICIPANTS: One hundred twenty‐one offspring of nonagenarian siblings, who were enriched for familial factors promoting longevity, and 113 of their partners. No subject had diabetes mellitus.MEASUREMENTS: Prevalence of metabolic syndrome was determined according to the criteria of the Third Report of the National Cholesterol Education Program. Glucose tolerance was assessed according to a 2‐hour oral glucose tolerance test.RESULTS: The offspring of nonagenarians siblings had a lower prevalence of metabolic syndrome (P=.03), similar body composition, lower mean fasting blood glucose levels (4.99 vs 5.16 mmol/L; P=.01), lower mean fasting insulin levels (5.81 vs 6.75 mU/L; P=.04), a higher mean homeostasis model assessment of insulin sensitivity (0.78 vs 0.65; P=.02), and a more‐favorable glucose tolerance (mean area under the receiver operating characteristic curve for glucose (13.2 vs 14.3; P=.007) than their partners. No significant differences were observed between the offspring and their partners in β‐cell function (insulogenic index 13.6 vs 12.5; P=.38).CONCLUSION: Despite similar body composition, the offspring of nonagenarian siblings showed a lower prevalence of metabolic syndrome and better glucose tolerance than their partners, centralizing the role of favorable glucose metabolism in familial longevity.
Choice of Initial Antiepileptic Drug for Older Veterans: Possible Pharmacokinetic Drug Interactions with Existing Medications
Authors: Pugh Mary Jo V. , VanCott Anne C. , Steinman Michael A. , Mortensen Eric M. , Amuan Megan E. , Wang Chen‐Pin , Knoefel Janice E. , Berlowitz Dan R. 
Published: March 2010

OBJECTIVES: To identify clinically meaningful potential drug–drug interactions (PDIs) with antiepileptic drugs (AEDs), the AEDs and co‐administered drugs commonly associated with AED‐PDIs, and characteristics of patients with high likelihood of AED‐PDI exposure.DESIGN: Five‐year retrospective cohort study of veterans with new‐onset epilepsy.SETTING: National Veterans Affairs and Medicare databases.PARTICIPANTS: Veterans aged 66 and older with a new diagnosis of epilepsy between October 1, 1999, and September 30, 2004 (N=9,682).MEASUREMENTS: AED‐PDI was restricted to clinically meaningful PDIs identified using prior literature review. AED‐PDIs were identified using participants' date of initial AED prescription and overlapping concomitant medications. Logistic regression analysis identified factors associated with AED‐PDI, including demographic characteristics, chronic disease states, and diagnostic setting.RESULTS: AED‐PDI exposure was found in 45.5% (4,406/9,682); phenytoin, a drug with many PDIs, was the most commonly prescribed AED. Cardiovascular drugs, lipid‐lowering medications, and psychotropic agents were the most commonly co‐administered AED‐PDI medications. Individuals with AED‐PDI exposure were more likely to have hypertension (odds ratio (OR)=1.46, 99% confidence interval (CI)=1.24–1.82) and hypercholesterolemia (OR=1.40, 99% CI=1.24–1.57) than those without and to be diagnosed in an emergency or primary care setting than a neurology setting (emergency: OR=1.30, 99% CI=1.08–1.58; primary care: OR=1.29 99% CI=1.12–1.49).CONCLUSION: Exposure to AED‐PDI was substantial but less common in patients with epilepsy diagnosed in a neurology setting. Because potential outcomes associated with AED‐PDI include stroke and myocardial infarction in a population already at high risk, clinicians should closely monitor blood pressure, coagulation, and lipid measures to minimize adverse effects of AED‐PDIs. Interventions to reduce AED‐PDIs may improve patient outcomes.
Frequency and Correlates of Caregiver‐Reported Sleep Disturbances in a Sample of Persons with Early Dementia
Authors: Rongve Arvid , Boeve Bradley F. , Aarsland Dag 
Published: March 2010

OBJECTIVES: To identify sleep disturbances in participants with subtypes of dementia and explore clinical correlates.DESIGN: Cross‐sectional.SETTING: Outpatient clinics in western Norway and the Mayo Clinic Study of Aging, Olmsted County, Minnesota.PARTICIPANTS: One hundred fifty‐one community‐dwelling western Norway residents referred for geriatric medicine, geriatric psychiatry or neurology evaluation and 420 participants without dementia from the Mayo Clinic Study of Aging.MEASUREMENTS: Dementia was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. The Mayo Sleep Questionnaire, an interview to detect sleep disturbances, was administered to diagnose probable rapid eye movement (REM) sleep behavior disorder, probable periodic leg movements during sleep, probable restless legs syndrome, probable sleepwalking, probable sleep‐related leg cramps, probable obstructive sleep apnea, and excessive daytime sleepiness. Insomnia was assessed using the Neuropsychiatric Inventory, an interview to detect neuropsychiatric symptoms in dementia.RESULTS: Seventy‐one percent of the participants with dementia and 55.7% of control participants had sleep disturbances (P=.001). Most frequently reported in the mild dementia participants were insomnia (29.9%), probable sleep‐related leg cramps (24.1%), excessive daytime sleepiness (22.6%), probable restless legs syndrome (20.7%), and probable REM sleep behavior disorder (18.5%). There were more sleep‐related problems reported in participants with Lewy body dementias (LBD) (dementia with Lewy bodies and Parkinson's disease dementia) than in those with Alzheimer's disease (P=.008). Having any sleep disorder correlated with depression (P=.03) and anxiety (P=.02).CONCLUSION: Sleep problems are common in dementia, particularly in subjects with LBD, and are associated with psychiatric symptoms. Further research is needed to understand these associations and identify treatment strategies.
Quality‐of‐Life Trajectories at the End of Life: Assessments over Time by Patients with and without Cancer
Authors: Downey Lois , Engelberg Ruth A. 
Published: March 2010

OBJECTIVES: To compare quality‐of‐life (QOL) ratings of terminally ill patients with and without cancer over time.DESIGN: Secondary analysis of prospective data from a randomized clinical trial.SETTING: Trial conducted with terminally ill patients in Seattle, Washington, testing the efficacy of massage and guided meditation in improving patients' QOL.PARTICIPANTS: One hundred sixty‐seven trial participants, of whom 127 provided follow‐up data and died before data analysis.MEASUREMENTS: At enrollment, participants reported demographic characteristics, symptom distress, QOL, and primary life‐limiting diagnosis. At enrollment and at follow‐up interviews after every two study‐provided treatment sessions, participants rated their perceived quality of life on a scale from 0 (no quality of life) to 10 (perfect quality). At the end of the study, the investigators added measures of patient's survival status, number of days between study enrollment and death, and receipt of hospice services to the data set.RESULTS: Multilevel models showed significantly steeper QOL declines for patients with cancer than for those without after adjustment for time between study enrollment and death. Over a 4‐month before‐death period, the average patient without cancer was estimated to experience a QOL decline of approximately 0.6 on a scale from 0 to 10, compared with a 1.2‐point decline for patients with cancer.CONCLUSION: Patients with cancer face more‐precipitous end‐of‐life challenges to quality of life than do other terminally ill persons. Therefore, clinicians must address QOL issues—not just symptom burden and distress. By introducing and discussing expected QOL declines at the end of life, clinicians may help to prepare, support, and reassure patients and their families.
Pragmatic, Cluster Randomized Trial of a Policy to Introduce Low‐Low Beds to Hospital Wards for the Prevention of Falls and Fall Injuries
Authors: Haines Terry P. , Bell Rebecca A.R. , Varghese Paul N. 
Published: March 2010

OBJECTIVES: To evaluate the efficacy of a policy to introduce low‐low beds for the prevention of falls and fall injuries on wards that had not previously accessed low‐low beds.DESIGN: This was a pragmatic, matched, cluster randomized trial with wards paired according to rate of falls. Intervention and control wards were observed for a 6‐month period after implementation of the low‐low beds on the intervention wards. Data from a 6‐month period before this were also collected and included in analyses to ensure comparability between intervention and control group wards.SETTING: Public hospitals located in Queensland, Australia.PARTICIPANTS: Patients of 18 public hospital wards.INTERVENTION: Provision of one low‐low bed for every 12 on a hospital ward, with written guidance for identifying patients at greatest risk of falls.MEASUREMENTS: Falls and fall injuries in the hospital measured using a computerized incident reporting system.RESULTS: There were 10,937 admissions to control and intervention wards combined during the pre‐intervention period. There was no significant difference in the rate of falls per 1,000 occupied bed days between intervention and control group wards after the introduction of the low‐low beds (generalized estimating equation coefficient=0.23, 95% confidence interval=−0.18–0.65, P=.28). The rate of bed falls, falls resulting in injury, and falls resulting in fracture also did not differ between groups. Some difficulties were encountered in intervention group wards in using the low‐low beds as directed.CONCLUSION: A policy for the introduction of low‐low beds did not appear to reduce falls or falls with injury, although larger studies would be required to determine their effect on fall‐related fractures.
Frequency and Pattern of Emergency Department Visits by Long‐Term Care Residents—A Population‐Based Study
Authors: Gruneir Andrea , Bell Chaim M. , Bronskill Susan E. , Schull Michael , Anderson Geoffrey M. , Rochon Paula A. 
Published: March 2010

OBJECTIVES: To obtain population‐based estimates of emergency department (ED) visits by long‐term care (LTC) residents.DESIGN: Retrospective cohort study using administrative data.SETTING: All LTC facilities in Ontario, Canada.PARTICIPANTS: All LTC residents who visited an ED at least once during a 6‐month period.MEASUREMENTS: All ED visits were described using the National Ambulatory Care Reporting System. Two distinct visit types were defined. Potentially preventable visits were defined as those for any ambulatory care sensitive condition; these are conditions for which exacerbations that result in hospital use suggest lack of access to adequate primary care. Low‐acuity visits were defined as those triaged as nonurgent at ED registration and ended with return to the LTC facility without hospital admission.RESULTS: Nearly one‐quarter of LTC residents visited the ED at least once in 6 months. Of all visits, 24.6% were for a potentially preventable reason, most commonly pneumonia, urinary tract infection, and congestive heart failure. These visits had a high frequency of ambulance transport (90.4%), emergent triage (35.3%), hospital admission (62.4%), and death within 30 days (23.6%). Of all visits, 11.0% were low acuity. Fall‐related injury was the most common cause. Low‐acuity visits were the shortest (mean length 4.5 ± 4.0 hours) and had the lowest frequency of death within 30 days (4.3%).CONCLUSION: LTC residents made frequent visits to the ED. The visit types showed distinct patterns that suggest a need for better access to medical care for common conditions and a greater emphasis on fall prevention in LTC.
Screening for Abuse and Neglect of People with Dementia
Authors: Wiglesworth Aileen , Mosqueda Laura , Mulnard Ruth , Liao Solomon , Gibbs Lisa , Fitzgerald William 
Published: March 2010

OBJECTIVE: To investigate characteristics of people with dementia and their caregivers (CGs) that are associated with mistreatment in order to inform clinicians about screening for mistreatment.DESIGN: A convenience sample of CG–care recipient (CR) dyads were assessed for literature‐supported factors associated with mistreatment, and evidence of mistreatment for the prior year was collected. An expert panel considered the evidence and decided on occurrences of psychological abuse, physical abuse, and neglect based on criteria adopted before data collection.SETTING: Participants' homes.PARTICIPANTS: One hundred twenty‐nine persons with dementia and their CGs.MEASUREMENTS: CG and CR characteristics (demographic, health, and psychosocial variables), relationship characteristics, and three elder abuse and neglect detection instruments.RESULTS: Mistreatment was detected in 47.3%. Variables associated with different kinds and combinations of mistreatment types included the CG's anxiety, depressive symptoms, social contacts, perceived burden, emotional status, and role limitations due to emotional problems and the CR's psychological aggression and physical assault behaviors. The combination of CR's physical assault and psychological aggression provided the best sensitivity (75.4%) and specificity (70.6%) for elder mistreatment as defined by the expert panel. This finding has potential to be useful as a clinical screen for detecting mistreatment.CONCLUSIONS: The findings suggest important characteristics of older adults with dementia and their CGs that have potential for use in a clinical screening tool for elder mistreatment. Potential screening questions to be asked of CGs of people with dementia are suggested.
Serum Lipid Levels and Cognitive Change in Late Life
Authors: Reynolds Chandra A. , Gatz Margaret , Prince Jonathan A. , Berg Stig , Pedersen Nancy L. 
Published: March 2010

OBJECTIVES: To assess the effect of lipids and lipoproteins on longitudinal cognitive performance and cognitive health in late life and to consider moderating factors such as age and sex that may clarify conflicting prior evidence.DESIGN: Prospective cohort study.SETTING: A 16‐year longitudinal study of health and cognitive aging.PARTICIPANTS: Eight hundred nineteen adults from the Swedish Adoption Twin Study of Aging aged 50 and older at first cognitive testing, including 21 twin pairs discordant for dementia.MEASUREMENTS: Up to five occasions of cognitive measurements encompassing verbal, spatial, memory, and perceptual speed domains across a 16‐year span; baseline serum lipids and lipoproteins including high‐density lipoprotein cholesterol (HDL‐C), apolipoprotein (apo)A1, apoB, total serum cholesterol, and triglycerides.RESULTS: The effect of lipids on cognitive change was most evident before age 65. In women, higher HDL‐C and lower apoB and triglycerides predicted better maintenance of cognitive abilities, particularly verbal ability and perceptual speed, than age. Lipid values were less predictive of cognitive trajectories in men and, where observed, were in the contrary direction (i.e., higher total cholesterol and apoB values predicted better perceptual speed performance though faster rates of decline). In twin pairs discordant for dementia, higher total cholesterol and apoB levels were observed in the twin who subsequently developed dementia.CONCLUSION: High lipid levels may constitute a more important risk factor for cognitive health before age 65 than after. Findings for women are consistent with clinical recommendations, whereas for men, the findings correspond with earlier age‐associated shifts in lipid profiles and the importance of lipid homeostasis to cognitive health.
Influence of Microwave Disinfection on the Dimensional Stability of Denture Reline Polymers
Authors: Basso Michael Frederico Manzolli , Giampaolo Eunice Teresinha , Vergani Carlos Eduardo , Machado Ana Lúcia , Pavarina Ana Cláudia , Ribeiro Roberta Chuqui 
Published: March 2010

Abstract Purpose: The purpose of this study was to evaluate the effect of microwave disinfection (3 minutes at 650 W) on the dimensional stability of hard chairside reline resins (Kooliner, Tokuyama Rebase II, Ufi Gel hard, New Truliner) and one heat‐polymerizing denture base resin (Lucitone 550). Materials and Methods: A split mold with reference points was used to make specimens (50.0‐mm diameter, 0.5‐mm thick) from each material, divided into five test groups (n = 8). The distances between the points on the mold were measured (gold standard), and compared with those obtained from the specimens after polymerization (baseline readings) after one, two, three, and four cycles of disinfection by microwave irradiation. Results: ANOVA and Tukey tests (α= 0.05) showed that Kooliner was significantly affected by all disinfection cycles (p < 0.05) when compared with baseline measurements. New Truliner resin was significantly affected by three and four cycles of microwave disinfection when compared with baseline measurements (p < 0.05). For Tokuyama Rebase II, Ufi Gel hard, and Lucitone 550, no significant dimensional changes were found. Conclusions: Microwave disinfection promoted shrinkage of Kooliner and New Truliner. The dimensional stability of Tokuyama Rebase II, Ufi Gel Hard, and Lucitone 550 was not affected by microwave disinfection.