bluuebunny/crossref_metadata_2025 huggingface dataset:
Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and chronic opiate treatments
Authors: Elhabazi K , Trigo JM , Mollereau C , Moulédous L , Zajac J‐M , Bihel F , Schmitt M , Bourguignon JJ , Meziane H , Petit‐demoulière B , Bockel F , Maldonado R , Simonin F
Published: June 2011

BACKGROUND AND PURPOSE Opiates remain the most effective compounds for alleviating severe pain across a wide range of conditions. However, their use is associated with significant side effects. Neuropeptide FF (NPFF) receptors have been implicated in several opiate‐induced neuroadaptive changes including the development of tolerance. In this study, we investigated the consequences of NPFF receptor blockade on acute and chronic stimulation of opioid receptors in mice by using RF9, a potent and selective antagonist of NPFF receptors that can be administered systemically.

EXPERIMENTAL APPROACH The effects of RF9 were investigated on opioid pharmacological responses including locomotor activity, antinociception, opioid‐induced hyperalgesia, rewarding properties and physical dependence.

KEY RESULTS RF9 had no effect on morphine‐induced horizontal hyperlocomotion and slightly attenuated the decrease induced in vertical activity. Furthermore, RF9 dose‐dependently blocked the long‐lasting hyperalgesia produced by either acute fentanyl or chronic morphine administration. RF9 also potentiated opiate early analgesic effects and prevented the development of morphine tolerance. Finally, RF9 increased morphine‐induced conditioned place preference without producing any rewarding effect by itself and decreased naltrexone‐precipitated withdrawal syndrome following chronic morphine treatment.

CONCLUSION AND IMPLICATIONS The NPFF system is involved in the development of two major undesirable effects: tolerance and dependence, which are clinically associated with prolonged exposure to opiates. Our findings suggest that NPFF receptors are interesting therapeutic targets to improve the analgesic efficacy of opiates by limiting the development of tolerance, and for the treatment of opioid dependence.
OX1 orexin/hypocretin receptor activation of phospholipase D
Authors: Jäntti MH , Putula J , Somerharju P , Frohman MA , Kukkonen JP
Published: June 2011

BACKGROUND AND PURPOSE

Orexin receptors potently signal to lipid messenger systems, and our previous studies have suggested that PLD would be one of these. We thus wanted to verify this by direct measurements and clarify the molecular mechanism of the coupling.

EXPERIMENTAL APPROACH

Orexin receptor‐mediated PLD activation was investigated in CHO cells stably expressing human OX1 orexin receptors using [14C]‐oleic acid‐prelabelling and the transphosphatidylation assay.

KEY RESULTS

Orexin stimulation strongly increased PLD activity – even more so than the phorbol ester TPA (12‐O‐tetradecanoyl‐phorbol‐13‐acetate), a highly potent activator of PLD. Both orexin and TPA responses were mediated by PLD1. Orexin‐A and ‐B showed approximately 10‐fold difference in potency, and the concentration–response curves were biphasic. Using pharmacological inhibitors and activators, both orexin and TPA were shown to signal to PLD1 via the novel PKC isoform, PKCδ. In contrast, pharmacological or molecular biological inhibitors of Rho family proteins RhoA/B/C, cdc42 and Rac did not inhibit the orexin (or the TPA) response, nor did the molecular biological inhibitors of PKD. In addition, neither cAMP elevation, Gαi/o nor Gβγ seemed to play an important role in the orexin response.

CONCLUSIONS AND IMPLICATIONS

Stimulation of OX1 receptors potently activates PLD (probably PLD1) in CHO cells and this is mediated by PKCδ but not other PKC isoforms, PKDs or Rho family G‐proteins. At present, the physiological significance of orexin‐induced PLD activation is unknown, but this is not the first time we have identified PKCδ in orexin signalling, and thus some specific signalling cascade may exist between orexin receptors and PKCδ.
Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/CXCR2 non‐competitive allosteric inhibitor
Authors: Bertini R , Barcelos LS , Beccari AR , Cavalieri B , Moriconi A , Bizzarri C , Di Benedetto P , Di Giacinto C , Gloaguen I , Galliera E , Corsi MM , Russo RC , Andrade SP , Cesta MC , Nano G , Aramini A , Cutrin JC , Locati M , Allegretti M , Teixeira MM
Published: June 2011

BACKGROUND AND PURPOSE DF 2156A is a new dual inhibitor of IL‐8 receptors CXCR1 and CXCR2 with an optimal pharmacokinetic profile. We characterized its binding mode, molecular mechanism of action and selectivity, and evaluated its therapeutic potential.

EXPERIMENTAL APPROACH The binding mode, molecular mechanism of action and selectivity were investigated using chemotaxis of L1.2 transfectants and human leucocytes, in addition to radioligand and [35S]‐GTPγS binding approaches. The therapeutic potential of DF 2156A was evaluated in acute (liver ischaemia and reperfusion) and chronic (sponge‐induced angiogenesis) experimental models of inflammation.

KEY RESULTS A network of polar interactions stabilized by a direct ionic bond between DF 2156A and Lys99 on CXCR1 and the non‐conserved residue Asp293 on CXCR2 are the key determinants of DF 2156A binding. DF 2156A acted as a non‐competitive allosteric inhibitor blocking the signal transduction leading to chemotaxis without altering the binding affinity of natural ligands. DF 2156A effectively and selectively inhibited CXCR1/CXCR2‐mediated chemotaxis of L1.2 transfectants and leucocytes. In a murine model of sponge‐induced angiogenesis, DF 2156A reduced leucocyte influx, TNF‐α production and neovessel formation. In vitro, DF 2156A prevented proliferation, migration and capillary‐like organization of HUVECs in response to human IL‐8. In a rat model of liver ischaemia and reperfusion (I/R) injury, DF 2156A decreased PMN and monocyte‐macrophage infiltration and associated hepatocellular injury.

CONCLUSION AND IMPLICATIONS DF 2156A is a non‐competitive allosteric inhibitor of both IL‐8 receptors CXCR1 and CXCR2. It prevented experimental angiogenesis and hepatic I/R injury in vivo and, therefore, has therapeutic potential for acute and chronic inflammatory diseases.
Emodin induces chloride secretion in rat distal colon through activation of mast cells and enteric neurons
Authors: Xu J‐D , Liu S , Wang W , Li L‐S , Li X‐F , Li Y , Guo H , Ji T , Feng X‐Y , Hou X‐L , Zhang Y , Zhu J‐X
Published: June 2011

BACKGROUND AND PURPOSE Emodin (1,3,8‐trihydroxy‐6‐methylanthraquinone) is an active component of many herb‐based laxatives. However, its mechanism of action is unclear. The aim of the present study was to investigate the role of mast cells and enteric neurons in emodin‐induced ion secretion in the rat colon.

EXPERIMENTAL APPROACH Short‐circuit current (ISC) recording was used to measure epithelial ion transport. A scanning ion‐selective electrode technique was used to directly measure Cl‐ flux (JCl−) across the epithelium. RIA was used to measure emodin‐induced histamine release.

KEY RESULTS Basolateral addition of emodin induced a concentration‐dependent increase in ISC in colonic mucosa/submucosa preparations, EC50 75 µM. The effect of emodin was blocked by apically applied glibenclamide, a Cl‐ channel blocker, and by basolateral application of bumetanide, an inhibitor of the Na+‐K+‐2Cl‐ cotransporter. Emodin‐evoked JCl− in mucosa/submucosa preparations was measured by scanning ion‐selective electrode technique, which correlated to the increase in ISC and was significantly suppressed by glibenclamide and bumetanide. Pretreatment with tetrodotoxin and the muscarinic receptor antagonist atropine had no effect on emodin‐induced ΔISC in mucosa‐only preparations, but significantly reduced emodin‐induced ΔISC and JCl− in mucosa/submucosa preparations. The COX inhibitor indomethacin, the mast cell stabilizer ketotifen and H1 receptor antagonist pyrilamine significantly reduced emodin‐induced ΔISC in mucosa and mucosa/submucosa preparations. The H2 receptor antagonist cimetidine inhibited emodin‐induced ΔISC and JCl− only in the mucosa/submucosa preparations. Furthermore, emodin increased histamine release from the colonic mucosa/submucosa tissues.

CONCLUSIONS AND IMPLICATIONS The results suggest that emodin‐induced colonic Cl‐ secretion involves mast cell degranulation and activation of cholinergic and non‐cholinergic submucosal neurons.
Hepatic aflatoxin B1‐DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan
Authors: Shirabe Ken , Toshima Takeo , Taketomi Akinobu , Taguchi Kennichi , Yoshizumi Tomoharu , Uchiyama Hideaki , Harimoto Norifumi , Kajiyama Kiyoshi , Egashira Akinori , Maehara Yoshihiko
Published: June 2011

Background & aims: Hepatitis B or C virus infection is considered to be the main cause of hepatocellular carcinoma (HCC) in Japan. Aflatoxin B1 (AFB1) is a carcinogen associated with HCC in regions with high exposure. Mutations in codon 249, exon 7 are a hallmark of AFB1 exposure. Therefore, to clarify the role of AFB1 in hepatocarcinogenesis, we examined AFB1‐DNA in liver tissue and sequenced TP53 in Japanese patients with HCC.

Methods: Hepatocyte AFB1‐DNA adducts were determined immunohistochemically and direct sequencing of TP53 was done to determine mutations in 188 of 279 patients who underwent hepatic resection for HCC. We assessed hepatitis C virus antibodies (HCV Ab) and HBSAg expression; patients without either were defined as having non‐B non‐C hepatocellular carcinoma (NBNC HCC).

Results: AFB1‐DNA adducts were detected in hepatocyte nuclei in 18/279 patients (6%), including13/83 patients (16%) with NBNC HCC and 5/51 patients (10%) expressing hepatitis B surface antigen. None of the patients with HCV Ab (n=136) were positive for AFB1‐DNA. The incidence of the G–T transversion and mutations in exon 7 of TP53 in patients with AFB1‐DNA adducts were significantly higher in patients with than in patients without AFB1‐DNA adducts. All three patients with the codon 249 AGG–AGT mutation had AFB1‐DNA adducts.

Conclusion: Although exposure to AFB1 is thought to be low in Japan, it is still associated with hepatocarcinogenesis, particularly in NBNC HCC and hepatitis B individuals.
A systems biology approach for understanding the collagen regulatory network in alcoholic liver disease
Authors: Nieto Natalia
Published: June 2011

Among the pathogenesis and risk factors of alcoholic liver disease (ALD) are the source of dietary fat, obesity, insulin resistance, adipokines and acetaldehyde. Translocation of Gram‐negative bacteria from the gut, the subsequent effects mediated by endotoxin, and the increased production of matricellular proteins, cytokines, chemokines and growth factors, actively participate in the progression of liver injury. In addition, generation of reactive oxygen and nitrogen species and the activation of non‐parenchymal cells also contribute to the pathophysiology of ALD. A key event leading to liver damage is the transition of quiescent hepatic stellate cells into activated myofibroblasts, with the consequent deposition of fibrillar collagen I resulting in significant scarring. Thus, it is becoming clearer that matricellular proteins are critical players in the pathophysiology of liver disease; however, additional mechanistic insight is needed to understand the signalling pathways involved in the up‐regulation of collagen I protein. At present, systems biology approaches are helping to answer the many unresolved questions in this field and are allowing to more comprehensively identify protein networks regulating pathological collagen I deposition in hopes of determining how to prevent the onset of liver fibrosis and/or to slow disease progression. Thus, this review article provides a snapshot on current efforts for identifying pathological protein regulatory networks in the liver using systems biology tools. These approaches hold great promise for future research in liver disease.
Long‐term effect of maternal HBeAg on delayed HBeAg seroconversion in offspring with chronic hepatitis B infection
Authors: Tseng Yu‐Ru , Wu Jia‐Feng , Ni Yen‐Hsuan , Chen Huey‐Ling , Chen Chih‐Cheng , Wen Wan‐Hsin , Hsu Hong‐Yuan , Chang Mei‐Hwei
Published: June 2011

Background and aims: This cohort study investigated the long‐term effect of maternal hepatitis B virus (HBV) sero‐status on the spontaneous HBeAg seroconversion in offspring with chronic HBV infection.

Methods: A total of 185 HBeAg‐positive chronic HBV‐infected children, with maternal HBV seromarkers checked, were enrolled. The median age at enrolment and follow‐up duration was 5.7 years (range, neonate to 16.5 years) and 20.2 years (range, 4.2–31.0 years) respectively. These children were grouped according to the initial maternal HBsAg and HBeAg status: (i) children of non‐carrier mothers (n=48); (ii) children of HBeAg‐negative chronic HBV‐infected mothers (n=57); (iii) children of HBeAg‐positive chronic HBV‐infected mothers (n=80). HBV seromarkers and liver function profiles of these children were performed at 6‐month intervals.

Results: One hundred and twenty‐one (65.4%) subjects had achieved spontaneous HBeAg seroconversion at the end of this follow‐up study. Spontaneous HBeAg seroconversion was achieved in 83.3% of children with non‐carrier mothers, 73.7% of children with HBeAg‐negative chronic HBV‐infected mothers and 48.8% of children with HBeAg‐positive mothers during similar duration (P<0.001). Positive maternal HBeAg and genotype C were associated with delayed spontaneous HBeAg seroconversion in multivariate analysis (P=0.01 and P=0.002 respectively). In children of HBeAg‐positive chronic HBV‐infected mothers, persistent presence of maternal HBeAg showed a trend of association with delayed HBeAg seroconversion in their offspring (P=0.06). Children of late maternal HBeAg seroconversion (>40 years old) had delayed HBeAg seroconversion compared with those of early HBeAg seroconversion mothers (P=0.06).

Conclusions: Persistence of maternal HBeAg is an important risk factor for delayed spontaneous HBeAg seroconversion in children with chronic HBV infection.
Tooth Tissue Engineering: Optimal Dental Stem Cell Harvest Based on Tooth Development
Authors: Duailibi Monica Talarico , Duailibi Silvio Eduardo , Duailibi Neto Eduardo Felippe , Negreiros Renata Matalon , Jorge Waldyr Antonio , Ferreira Lydia Masako , Vacanti Joseph Phillip , Yelick Pamela Crotty
Published: June 2011

Our long‐term objective is to devise reliable methods to generate biological replacement teeth exhibiting the physical properties and functions of naturally formed human teeth. Previously, we demonstrated the successful use of tissue engineering approaches to generate small, bioengineered tooth crowns from harvested pig and rat postnatal dental stem cells (DSCs). To facilitate characterizations of human DSCs, we have developed a novel radiographic staging system to accurately correlate human third molar tooth developmental stage with anticipated harvested DSC yield. Our results demonstrated that DSC yields were higher in less developed teeth (Stages 1 and 2), and lower in more developed teeth (Stages 3, 4, and 5). The greatest cell yields and colony‐forming units (CFUs) capability was obtained from Stages 1 and 2 tooth dental pulp. We conclude that radiographic developmental staging can be used to accurately assess the utility of harvested human teeth for future dental tissue engineering applications.
Natural‐Channel‐Design Restorations That Changed Geomorphology Have Little Effect on Macroinvertebrate Communities in Headwater Streams
Authors: Ernst Anne G. , Warren Dana R. , Baldigo Barry P.
Published: June 2011

Stream restorations that increase geomorphic stability can improve habitat quality, which should benefit selected species and local aquatic ecosystems. This assumption is often used to define primary restoration goals; yet, biological responses to restoration are rarely monitored or evaluated methodically. Macroinvertebrate communities were inventoried at 6 study reaches within 5 Catskill Mountain streams between 2002 and 2006 to characterize their responses to natural‐channel‐design (NCD) restoration. Although bank stability increased significantly at most restored reaches, analyses of variation showed that NCD restorations had no significant effect on 15 of 16 macroinvertebrate community metrics. Multidimensional scaling ordination indicated that communities from all reach types within a stream were much more similar to each other within any given year than they were in the same reaches across years or within any type of reach across streams. These findings indicate that source populations and watershed‐scale factors were more important to macroinvertebrate community characteristics than were changes in channel geomorphology associated with NCD restoration. Furthermore, the response of macroinvertebrates to restoration cannot always be used to infer the response of other stream biota to restoration. Thus, a broad perspective is needed to characterize and evaluate the full range of effects that restoration can have on stream ecosystems.
Non‐Native Grass Removal and Shade Increase Soil Moisture and Seedling Performance during Hawaiian Dry Forest Restoration
Authors: Thaxton Jarrod M. , Cordell Susan , Cabin Robert J. , Sandquist Darren R.
Published: June 2011

Invasive non‐native species can create especially problematic restoration barriers in subtropical and tropical dry forests. Native dry forests in Hawaii presently cover less than 10% of their original area. Many sites that historically supported dry forest are now completely dominated by non‐native species, particularly grasses. Within a grass‐dominated site in leeward Hawaii, we explored the mechanisms by which non‐native Pennisetum setaceum, African fountain grass, limits seedlings of native species. We planted 1,800 seedlings of five native trees, three native shrubs, and two native vines into a factorial field experiment to examine the effects of grass removal (bulldozed vs. clipped plus herbicide vs. control), shade (60% shade vs. full sun), and water (supplemental vs. ambient) on seedling survival, growth, and physiology. Both grass removal and shade independently increased survival and growth, as well as soil moisture. Seedling survival and relative growth rate were also significantly dependent on soil moisture. These results suggest that altering soil moisture may be one of the primary mechanisms by which grasses limit native seedlings. Grass removal increased foliar nitrogen content of seedlings, which resulted in an increase in leaf‐level photosynthesis and intrinsic water use efficiency. Thus in the absence of grasses, native species showed increased productivity and resource acquisition. We conclude that the combination of grass removal and shading may be an effective approach to the restoration of degraded tropical dry forests in Hawaii and other ecologically similar ecosystems.
Incorporating Socio‐economic Factors into Restoration: Implications from Industrially Harvested Peatlands
Authors: Collier Marcus J.
Published: June 2011

In establishing effective restoration goals, one of the four key issues of increased attention that Hobbs calls for is in the area of incorporating socio‐economic investigations and theories into restoration practice in a synergistic manner. Although often commented upon by restoration practitioners, this is an area of research that is poorly developed, and because it relies on an uneasy combination of empirical and interpretative research methodologies a multidisciplinary alignment may be problematic in practice. This opinion piece is drawn from experiences in examining the after‐use of industrially mined peatland landscapes, and synthesizes ideas that have emerged from socio‐economic research over several years in order to offer an opinion on how Hobbs' call may be addressed. Because socio‐economic concerns are at the root of all restoration projects, sociological methods may be useful as tools in stakeholder engagement in research and planning for landscape rehabilitation as a mechanism for reducing the potential for conflict and for facilitating participative or collaborative restoration.
Outcomes of Displaced and Nondisplaced Pelvic and Sacral Fractures in Elderly Adults
Authors: Mears Simon C. , Berry Daniel J.
Published: June 2011

OBJECTIVES: To identify fracture types in a series of older adults with pelvic fractures and to determine whether the type of pelvic fracture affected short‐term outcomes and morbidity.

DESIGN: Retrospective chart review.

SETTING: Teaching hospital.

PARTICIPANTS: One hundred eighty‐one individuals aged 65 and older with low‐energy pelvic fractures.

MEASUREMENTS:

Fracture type, in‐hospital complications, mortality, maximal return to function, and return to living situation.

RESULTS: Of the 181 participants, 119 had unilateral displaced pubic rami fractures, 38 had nondisplaced pubic rami fractures, 14 had sacral insufficiency fractures, and 10 had bilateral displaced pubic rami fractures. There were no significant differences found in participant age; comorbidities; diagnosis of dementia; in‐hospital complications; or 30‐day, 90‐day, or 1‐year mortality rates between fracture types. Fracture type did not affect the ability of the participants to return home or their use of ambulatory aid.

CONCLUSION: For older adults, morbidity and mortality rates for nondisplaced pubic rami fractures and sacral insufficiency fractures are similar to those for displaced pelvic fractures.
Comparing Antidepressant Treatment Patterns in Older and Younger Adults: A Claims Database Analysis
Authors: Sanglier Thibaut , Saragoussi Delphine , Milea Dominique , Auray Jean‐Paul , Valuck Robert J. , Tournier Marie
Published: June 2011

OBJECTIVES: To compare depressed older (≥65) and younger (25–64) adults with regard to antidepressant treatment patterns and to assess factors associated with 180‐day nonpersistence.

DESIGN: Retrospective matched cohort study.

SETTING: U.S. managed care population.

PARTICIPANTS: Older and matched younger adults diagnosed with depression and treated with antidepressants.

MEASUREMENTS: Sociodemographic characteristics, comorbidities, polypharmacy, and characteristics of antidepressant treatment at 180 days were compared between older and younger adults. Analyses were conducted before and after the implementation of Medicare Part D on January 1, 2006, to consider the effect of this policy.

RESULTS: Few participants received psychotherapy, especially older ones; rates were constant before and after 2006. Before 2006, older adults more frequently received antidepressants at lower (odds ratio (OR)=5.38, 95% confidence interval (CI)=3.57–8.13) or intermediate dose (OR=2.42, 95% CI=1.93–3.02) and had poorer adherence to treatment (P<.001) than younger adults. After 2006, older adults received similar proportions of intermediate or high antidepressant doses as younger adults, but a lower dosage was still more likely to be prescribed (OR=1.87, 95% CI=1.09–3.20) and had higher treatment adherence (P<.001). Medication profile did not significantly affect the risk of nonpersistence, but increased with lower antidepressant dose (P<.001). Whereas nonpersistence was higher in older adults before 2006 (hazard ratio (HR)=1.25, 95% CI=1.22–1.46), the trend reversed after 2006 (HR=0.76, 95% CI=0.66–0.88).

CONCLUSION: More than half of participants with depression discontinued antidepressant treatment, and psychotherapy was rarely used. Implementation of Medicare Part D was associated with substantial changes in treatment of older adults with depression. The presence of comorbidities or polypharmacy was not associated with nonpersistence in depressed older adults.
Systematic Review and Meta‐Analysis: Do Clinical Trials Testing Antimuscarinic Agents for Overactive Bladder Adequately Measure Central Nervous System Adverse Events?
Authors: Paquette Amélie , Gou Pauline , Tannenbaum Cara
Published: June 2011

Experimental studies in healthy volunteers suggest that some antimuscarinic agents confer a risk of cognitive impairment, yet clinical trials of people with overactive bladder report only rare central nervous system (CNS) side effects. A lack of systematic measurement and reporting of CNS outcomes in clinical trials may partially explain this discrepancy. The purpose of this review and meta‐analysis was to ascertain the reporting bias associated with adverse CNS events in clinical drug trials of younger and older adults with overactive bladder. Articles were identified from MEDLINE and EMBASE databases until 2010 using the search terms “clinical trial” AND (one of) “oxybutynin, tolterodine, fesoterodine, propiverine, solifenacin, darifenacin, and trospium.” Eligibility criteria included original randomized trials involving adults with overactive bladder; standard doses of medication; reports of confusion, somnolence, sedation, dizziness, drowsiness, asthenia, insomnia, and vertigo; no evidence of dementia at baseline; and trials in English. Seventy‐seven percent (242/314) of eligible trials identified in the search neither measured nor reported CNS outcomes. Of the remaining 23%, it was difficult to distinguish whether CNS adverse events were systematically measured or spontaneously reported. Only one of 72 trials that were retained objectively measured changes in cognitive performance (Mini‐Mental State Examination). Dizziness was the most frequently reported side effect, in 3% of oxybutynin, 3.2% of propiverine, and 1.8% of tolterodine users, compared with 1.6% with placebo. Confusion was reported in fewer than 1% of cases. Age‐stratified analyses of CNS outcomes from trials in adults aged 65 and older with overactive bladder were found in only eight publications. Meta‐analyses were conducted with 33 randomized, double‐blind, placebo‐controlled trials to determine the effect of each drug and dose on different CNS outcomes. Study heterogeneity, dosing inconsistency, and reporting bias limited interpretation of the findings from the meta‐analyses. More‐detailed standardized measurement of age‐stratified CNS outcomes in clinical trials is required to better inform patients and clinicians about CNS risks associated with antimuscarinic agents.
Sustained Economic Benefits of Resistance Training in Community‐Dwelling Senior Women
Authors: Davis Jennifer C. , Marra Carlo A. , Robertson M. Clare , Najafzadeh Mehdi , Liu‐Ambrose Teresa
Published: June 2011

OBJECTIVES:

To determine whether the health and cost benefits of resistance training were sustained 12 months after formal cessation of the intervention.

DESIGN:Cost–utility analysis conducted alongside a randomized controlled trial.

SETTING:Community‐dwelling women aged 65 to 75 living in Vancouver, British Columbia.

PARTICIPANTS:One hundred twenty‐three of the 155 community‐dwelling women aged 65 to 75 years who originally were randomly allocated to once‐weekly resistance training (n=54), twice‐weekly resistance training (n=52), or twice‐weekly balance and tone exercises (control group; n=49) participated in the 12‐month follow‐up study. Of these, 98 took part in the economic evaluation (twice‐weekly balance and tone exercises, n=28; once‐weekly resistance training, n=35; twice‐weekly resistance training, n=35).

MEASUREMENTS:The primary outcome measure was incremental cost per quality‐adjusted life year (QALY) gained. Healthcare resource utilization was assessed over 21 months (2009 prices); health status was assessed using the EuroQol‐5D to calculate QALYs using a 21‐month time horizon.

RESULTS:Once‐ and twice‐weekly resistance training were less costly than balance and tone classes, with incremental mean healthcare costs of Canadian dollars (CAD$)1,857 and CAD$1,077, respectively. The incremental QALYs for once‐ and twice‐weekly resistance training were −0.051 and −0.081, respectively, compared with balance and tone exercises.

CONCLUSION:The cost benefits of participating in a 12‐month resistance training intervention were sustained for the once‐ and twice‐weekly resistance training group, whereas the health benefits were not.
Risk of Cerebrovascular Accident Associated with Use of Antipsychotics: Population‐Based Case–Control Study
Authors: Laredo Leonor , Vargas Emilio , Blasco Antonio Javier , Aguilar Maria Dolores , Moreno Alfonso , Portolés Antonio
Published: June 2011

OBJECTIVES: To explore the association between use of antipsychotics and risk of cerebrovascular accident (CVA) in individuals with dementia aged 65 and older.

DESIGN: Population‐based case–control study.

SETTING: UK‐based electronic primary care records in the General Practice Research Database (GPRD).

PARTICIPANTS: Individuals with dementia aged 65 and older registered in the database between January 1, 1995, and June 22, 2007.

MEASUREMENTS: Odds ratio (OR) of CVA in users versus nonusers of antipsychotics (typical or atypical) and in users of typical versus atypical antipsychotics. Multivariate analyses were performed using logistic regression models to adjust for potential confounders: demographic variables, comorbidity, and concomitant treatments.

RESULTS: After adjusting for confounding variables, the OR of CVA associated with use of only typical antipsychotics versus no antipsychotics in individuals with dementia aged 65 and older was 1.16 (95% confidence interval (CI)=1.07–1.27) and for use of only atypical antipsychotics versus no antipsychotics was 0.62 (95% CI=0.53–0.72). In the comparison of typical versus atypical antipsychotics, the OR was 1.83 (95% CI=1.57–2.14).

CONCLUSION: No reasons were found to question the cerebrovascular safety of atypical antipsychotics in older adults with dementia. The typical antipsychotics appear to be associated with a higher risk of CVA, although the risk disappears after use is discontinued.
Vulnerability of Older Latino and Asian Immigrants with Limited English Proficiency
Authors: Kim Giyeon , Worley Courtney B. , Allen Rebecca S. , Vinson Latrice , Crowther Martha R. , Parmelee Patricia , Chiriboga David A.
Published: June 2011

OBJECTIVES: To explore the implications of limited English proficiency (LEP) for disparities in health status and healthcare service use of older Latino and Asian immigrants.

DESIGN: Cross‐sectional analysis of existing secondary data.

SETTING: The 2007 California Health Interview Survey.

PARTICIPANTS: Latino and Asian immigrants aged 60 and older (n=1,745) were divided into three language proficiency groups: older adults who have LEP, are proficient in English but also speak another language at home (EP), and speak English only (EO).

MEASUREMENTS: Sociodemographic characteristics, health status, health service use, and barriers to service use were compared.

RESULTS: Older Latino and Asian immigrants with LEP tended to have poorer self‐rated health and higher psychological distress than the EP and EO groups. They were also less likely than the EP and EO groups to use health services and more likely to experience barriers to service use (e.g., difficulty understanding written information at the doctor's office).

CONCLUSION: Older Latinos and Asians with LEP are at higher risk for poor physical and mental health outcomes and inadequate health care. Healthcare systems should consider strategies to address the language needs of older immigrants to reduce the effect of linguistic disparities on access to care and ultimately to improve health status for these vulnerable populations.
Effect of a High‐Intensity Functional Exercise Program on Functional Balance: Preplanned Subgroup Analyses of a Randomized Controlled Trial in Residential Care Facilities
Authors: Littbrand Håkan , Carlsson Maine , Lundin‐Olsson Lillemor , Lindelöf Nina , Håglin Lena , Gustafson Yngve , Rosendahl Erik
Published: June 2011

OBJECTIVES: To evaluate whether age, sex, depression, dementia disorder, nutritional status, or level of functional balance capacity influences the effect of a high‐intensity functional weight‐bearing exercise program on functional balance.

DESIGN: Preplanned subgroup analyses of a randomized controlled trial.

SETTING: Nine residential care facilities.

PARTICIPANTS: One hundred ninety‐one people aged 65 to 100 dependent in activities of daily living and with Mini‐Mental State Examination scores of 10 or greater.

INTERVENTION: A high‐intensity functional weight‐bearing exercise program or a control activity, each comprising 29 sessions over 3 months.

MEASUREMENTS: Functional balance capacity was assessed blindly using the Berg Balance Scale (BBS) at baseline, 3 months, and 6 months. The BBS consists of 14 tasks, common in everyday life, such as standing up from sitting and, while standing, reaching forward or turning 360°. Interactions between allocation to activity group and each subgroup were evaluated according to the intention‐to‐treat principle.

RESULTS: The subgroup analyses revealed no statistically significant interaction for age, sex, depression, dementia disorder, nutritional status, or level of functional balance capacity at 3 (P=.65, .65, .51, .78, .09, .67, respectively) or 6 (P=.69, .62, .20, .94, .48, .85, respectively) months. In addition, at 3 and 6 months there was no significant interaction for cognitive level (P=.28, .47, respectively) or number of depressive symptoms (P=.85, .49, respectively).

CONCLUSION: Older age, female sex, depression, mild to moderate dementia syndrome, malnutrition, and severe physical impairment do not seem to have a negative effect on functional balance from a high‐intensity functional weight‐bearing exercise program. Consequently, people with these characteristics in residential care facilities should not be excluded from offers of rehabilitation including high‐intensity exercises.
Effect of an Inpatient Geriatric Consultation Team on Functional Outcome, Mortality, Institutionalization, and Readmission Rate in Older Adults with Hip Fracture: A Controlled Trial
Authors: Deschodt Mieke , Braes Tom , Broos Paul , Sermon An , Boonen Steven , Flamaing Johan , Milisen Koen
Published: June 2011

OBJECTIVES: To evaluate the effect of an inpatient geriatric consultation team (IGCT) on end points of interest in people with hip fracture: length of stay, functional status, mortality, new nursing home admission, and hospital readmission.

DESIGN: Controlled trial based on assignment by convenience.

SETTING: Trauma ward in a university hospital.

PARTICIPANTS: One hundred seventy‐one people with hip fracture aged 65 and older.

INTERVENTION: Participants were assigned to a multidisciplinary geriatric intervention (n=94) or usual care (n=77) during hospitalization after hip fracture.

MEASUREMENTS: End points were functional status, length of stay, mortality, new nursing home admission, and hospital readmission 6 weeks, 4 months, and 12 months after surgery.

RESULTS: Mean length of stay was 11.1 ± 5.1 days in the intervention group and 12.4 ± 8.5 days in the control groups (P=.24). Complete adherence to IGCT recommendations was 56.8%. A significant benefit of intervention on functional status in univariate analyses (P=.02) 8 days after surgery disappeared in a linear mixed model. Participants with dementia had better functional status in a linear mixed model than those without (P=.03), but this effect was no longer significant after Bonferroni correction for multiple testing. After 6 weeks, 4 months, and 12 months, no between‐group differences could be documented for mortality, new nursing home admission, or readmission rate.

CONCLUSION: This trial could not document functional benefits of an IGCT intervention in people with hip fracture. More research is needed to investigate whether a more‐intensive approach with more‐direct control over patient management, more‐specific recommendations, and more‐intense education would be effective.
White Matter Lesions on Brain Magnetic Resonance Imaging Scan and 5‐Year Cognitive Decline: The Honolulu‐Asia Aging Study
Authors: Inaba Michiko , White Lon , Bell Christina , Chen Randi , Petrovitch Helen , Launer Lenore , Abbott Robert D. , Ross G. Webster , Masaki Kamal
Published: June 2011

OBJECTIVES: To study white matter lesions (WMLs) and 5‐year cognitive decline in elderly Japanese‐American men.

DESIGN: Longitudinal cohort study.

SETTING: Population‐based study in Honolulu, Hawaii.

PARTICIPANTS: Japanese‐American men aged 74 to 95 from the Honolulu‐Asia Aging Study (HAAS) who were free of prevalent dementia, underwent a protocol brain MRI scan at the fifth HAAS examination (1994–1996), and returned for cognitive testing 5 years later (N=267).

MEASUREMENTS: WMLs were dichotomized as present (grade 3–9, 38.2%) or absent (grade 1–2, 61.8%). Cognitive function was measured using the Cognitive Abilities Screening Instrument (CASI), and 5‐year cognitive decline was defined as a drop in CASI score of 12 points or more (1 standard deviation).

RESULTS: Men with WMLs on MRI at baseline were significantly more likely to experience cognitive decline at 5 years than those without (22.4% vs 34.4%, P=.03). Using multiple logistic regression, adjusting for age, education, apolipoprotein (Apo)E4 allele, large or small infarcts on MRI, baseline CASI score, and hypertension, those with WMLs were significantly more likely to develop 5‐year cognitive decline (odds ratio=2.00, 95% confidence interval=1.10–3.65, P=.02). This association was stronger in men who were cognitively intact and free of the ApoE4 genotype and clinical stroke at baseline.

CONCLUSION: Presence of WMLs on MRI was significantly associated with higher odds of 5‐year cognitive decline in older Japanese‐American men. Presence of WMLs may help identify people at risk for developing dementia, who may benefit from early intervention.
Anticholinergic Medication Use and Cognitive Impairment in the Older Population: The Medical Research Council Cognitive Function and Ageing Study
Authors: Fox Chris , Richardson Kathryn , Maidment Ian D. , Savva George M. , Matthews Fiona E. , Smithard David , Coulton Simon , Katona Cornelius , Boustani Malaz A. , Brayne Carol
Published: June 2011

OBJECTIVES: To determine whether the use of medications with possible and definite anticholinergic activity increases the risk of cognitive impairment and mortality in older people and whether risk is cumulative.

DESIGN: A 2‐year longitudinal study of participants enrolled in the Medical Research Council Cognitive Function and Ageing Study between 1991 and 1993.

SETTING: Community‐dwelling and institutionalized participants.

PARTICIPANTS: Thirteen thousand four participants aged 65 and older.

MEASUREMENTS: Baseline use of possible or definite anticholinergics determined according to the Anticholinergic Cognitive Burden Scale and cognition determined using the Mini‐Mental State Examination (MMSE). The main outcome measure was decline in the MMSE score at 2 years.

RESULTS: At baseline, 47% of the population used a medication with possible anticholinergic properties, and 4% used a drug with definite anticholinergic properties. After adjusting for age, sex, educational level, social class, number of nonanticholinergic medications, number of comorbid health conditions, and cognitive performance at baseline, use of medication with definite anticholinergic effects was associated with a 0.33‐point greater decline in MMSE score (95% confidence interval (CI)=0.03–0.64, P=.03) than not taking anticholinergics, whereas the use of possible anticholinergics at baseline was not associated with further decline (0.02, 95% CI=−0.14–0.11, P=.79). Two‐year mortality was greater for those taking definite (OR=1.68; 95% CI=1.30–2.16; P<.001) and possible (OR=1.56; 95% CI=1.36–1.79; P<.001) anticholinergics.

CONCLUSION: The use of medications with anticholinergic activity increases the cumulative risk of cognitive impairment and mortality.
Risk Perception and Information Processing: The Development and Validation of a Questionnaire to Assess Self‐Reported Information Processing
Authors: Smerecnik Chris M. R. , Mesters Ilse , Candel Math J. J. M. , De Vries Hein , De Vries Nanne K.
Published: June 2011

The role of information processing in understanding people's responses to risk information has recently received substantial attention. One limitation of this research concerns the unavailability of a validated questionnaire of information processing. This article presents two studies in which we describe the development and validation of the Information‐Processing Questionnaire to meet that need. Study 1 describes the development and initial validation of the questionnaire. Participants were randomized to either a systematic processing or a heuristic processing condition after which they completed a manipulation check and the initial 15‐item questionnaire and again two weeks later. The questionnaire was subjected to factor reliability and validity analyses on both measurement times for purposes of cross‐validation of the results. A two‐factor solution was observed representing a systematic processing and a heuristic processing subscale. The resulting scale showed good reliability and validity, with the systematic condition scoring significantly higher on the systematic subscale and the heuristic processing condition significantly higher on the heuristic subscale. Study 2 sought to further validate the questionnaire in a field study. Results of the second study corresponded with those of Study 1 and provided further evidence of the validity of the Information‐Processing Questionnaire. The availability of this information‐processing scale will be a valuable asset for future research and may provide researchers with new research opportunities.
Reversing the Trend: The Recent Expansion of the Reverse Mortgage Market
Authors: Shan Hui
Published: June 2011

Reverse mortgages allow elderly homeowners to tap into their housing wealth without having to sell or move out of their homes. However, very few eligible homeowners used reverse mortgages to achieve consumption smoothing until recently, when the reverse mortgage market in the United States witnessed substantial growth. In this article, I examine 1989–2007 loan‐level reverse mortgage data and conduct three sets of analyses to better understand the demand for reverse mortgages among elderly homeowners. First, I study the ZIP code characteristics correlated with reverse mortgage originations. Second, I show that recent reverse mortgage borrowers are significantly different from earlier borrowers in many respects. Third, I investigate the reasons why the reverse mortgage market experienced substantial growth in the mid‐2000s. Combining the reverse mortgage data with county‐level house price data, I find that higher house prices lead to more reverse mortgage originations. Specifically, the increases in house prices account for about one‐third of the overall growth in the reverse mortgage market from 2003 to 2007.
Thy Neighbor’s Mortgage: Does Living in a Subprime Neighborhood Affect One’s Probability of Default?
Authors: Agarwal Sumit , Ambrose Brent W. , Chomsisengphet Souphala , Sanders Anthony B.
Published: June 2011

This article focuses on the potential externalities associated with subprime mortgage origination activity. Specifically, we examine whether negative spillover effects from subprime mortgage originations result in higher default rates in the surrounding area. Our empirical analysis controls for loan characteristics, house price changes and alternative loan products. Our results indicate that, after controlling for these characteristics, the concentration of subprime lending in a neighborhood does not lead to greater default risks for surrounding borrowers. However, we do find that more aggressive mortgage products (such as hybrid adjustable rate mortgages and low/no‐documentation loans) had significant negative spillovers on other borrowers. Stated differently, the aggressive alternative mortgage designs were more toxic to the housing and mortgage market than previously believed.
Ablation of Epicardial Right Ventricular Tachycardia Provoked by Proarrhythmic RV Pacing in a Patient with Dilated Cardiomyopathy
Authors: TANIGUCHI HIROSHI , UNO KIKUYA , KOMATSU YUKI , IESAKA YOSHITO
Published: June 2011

Ventricular arrhythmias are common in the setting of nonischemic dilated cardiomyopathy (NIDCM). However, the characterization of the substrate and mechanism of epicardial ventricular tachycardia (VT) associated with NIDCM is limited, and to the best of our knowledge VT due to myocardial reentry within the right ventricular (RV) epicardium associated with NIDCM has not been reported. We report a case of RV epicardial VT provoked by RV pacing that was successfully ablated. (PACE 2012; 35:e140–e143)
The 11th World Survey of Cardiac Pacing and Implantable Cardioverter‐Defibrillators: Calendar Year 2009–A World Society of Arrhythmia's Project
Authors: MOND HARRY G. , PROCLEMER ALESSANDRO
Published: June 2011

A worldwide cardiac pacing and implantable cardioverter‐defibrillator (ICD) survey was undertaken for calendar year 2009 and compared to a similar survey conducted in 2005. There were contributions from 61 countries: 25 from Europe, 20 from the Asia Pacific region, seven from the Middle East and Africa, and nine from the Americas. The 2009 survey involved 1,002,664 pacemakers, with 737,840 new implants and 264,824 replacements. The United States of America (USA) had the largest number of cardiac pacemaker implants (225,567) and Germany the highest new implants per million population (927). Virtually all countries showed increases in implant numbers over the 4 years between surveys. High‐degree atrioventricular block and sick sinus syndrome remain the major indications for implantation of a cardiac pacemaker. There remains a high percentage of VVI(R) pacing in the developing countries, although compared to the 2005 survey, virtually all countries had increased the percentage of DDDR implants. Pacing leads were predominantly transvenous, bipolar, and active fixation. The survey also involved 328,027 ICDs, with 222,407 new implants and 105,620 replacements. Virtually all countries surveyed showed a significant rise in the use of ICDs with the largest implanter being the USA (133,262) with 434 new implants per million population. This was the largest pacing and ICD survey ever performed, because of mainly a group of loyal enthusiastic survey coordinators. It encompasses more than 80% of all the pacemakers and ICDs implanted worldwide during 2009. (PACE 2011; 34:1013–1027)
The Hemodynamic Effect of Right Ventricle (RV), RT3DE Targeted Left Ventricle (LV) and Biventricular (BIV) Pacing in the Early Postoperative Period After Cardiac Surgery
Authors: STRAKA FRANTISEK , PIRK JAN , PINDAK MARIAN , SKALSKY IVO , VANCURA VLASTIMIL , CIHAK ROBERT , MAREK TOMAS , LUPINEK PETR , MASIN JAROSLAV , SCHORNIK DAVID , ZEMAN MICHAL , SKROBAKOVA JANKA , DORAZILOVA ZORA , SKIBOVA JELENA
Published: June 2011

Background: Congestive heart failure negatively impacts the prognosis in patients after cardiac surgery. The aim of our study was to assess the value of targeted cardiac resynchronization therapy (CRT) within 72 hours after cardiac surgery in patients with mechanical dyssynchrony, who had an ejection fraction ≤ 35%, QRS ≥150 ms or between 120 and 150 ms.

Methods: A prospective randomized trial based on three‐dimensional echocardiography (RT3DE) and optimized sequential dual‐chamber (DDD
) pacing in patients after cardiac surgery. DDD epicardial pacing (Medtronic coaxial epicardial leads 6495) was provided by a modified Medtronic INSYNC III Pacemaker (Medtronic Inc., Minneapolis, MN, USA).

Summary of results:
The study included 21 patients with ischemic heart disease (HD) or valvular HD (16 men, 5 women, average age 69 years) with left ventricle (LV) dysfunction after cardiac surgery
. Patients with biventricular (BIV) (CO 6.7 ± 1.7 L/min, CI 3.5 ± 0.8 L/min/m2) and LV (CO 6.2 ± 1.5 L/min, CI 3.2 ± 0.7 L/min/m2) pacing had statistically significantly higher CO and CI than patients with right ventricular (RV) (CO 5.4 ± 1.4 L/min, CI 2.8 ± 0.6 L/min/m2) pacing (BIV vs RV P ≤ 0.001; LV vs RV P ≤ 0.05; BIV vs LV P ≤ 0.05).

Conclusions: RT3DE targeted and optimized CRT in the early postperative period after cardiac surgery provided better hemodynamic results than RV pacing. (PACE 2011; 34:1231–1240)