bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of Toll‐Like Receptor 3 in Spleen is Associated with Experimental Arthritis in Rats
Authors: Zhu W. , Meng L. , Jiang C. , Xu J. , Wang B. , Han Y. , Lu S.
Published: June 2012

This study is to investigate the regulation of Toll‐like receptor (TLR) expression in systemic immune reactions in different arthritis rat models, which will provide evidence to understand the mechanisms of rheumatoid arthritis further. Arthritis‐susceptible DA rats were used to induce arthritis by pristane or collagen type II, and TLR2, 3, 4 and 7 expression levels in spleen were detected by real‐time quantitative polymerase chain reaction. TLR3 mRNA expression in spleen of both collagen‐induced arthritis and pristane‐induced arthritis (PIA) rats was increased significantly at 26 and 70 days after arthritis induction. The overexpression of TLR3 was confirmed by Western blotting. Methotrexate was administrated peritoneally to PIA rats, and phytol was applied subcutaneously to PIA rats. Both methotrexate and phytol treatment could alleviate arthritis severity and block TLR3 induction. However, in arthritis‐resistant E3 rats injected with pristane, TLR3 expression of spleen was unaltered. PIA in MHC congenic DA.1U rats had mild symptoms, whereas TLR3 mRNA expression in spleen of DA.1U rats showed an impaired induction at D26. So we conclude that overexpression of splenic TLR3 is strongly associated with arthritis in rats, which suggests that TLR3 should be a most vital TLR in spleen to regulate the initiation and development of experimental arthritis and may be as an intriguing therapeutic opportunity for human rheumatoid arthritis.
Sindbis Virus Replicase‐based DNA Vaccine Construct Encoding FMDV‐specific Multivalent Epitope Gene: Studies on its Immune Responses in Guinea Pigs
Authors: Dar P. A. , Ganesh K. , Nagarajan G. , Sarika S. , Reddy G. R. , Suryanarayana V. V. S.
Published: June 2012

Foot‐and‐mouth disease (FMD) is still a perennial global menace affecting livestock health and production. It is imperative to figure out new ways to curb this disease. In this study, a sindbis virus replicase‐based DNA vaccine, pSinCMV‐Vac‐MEG990, encoding a multivalent epitope gene (representing tandemly linked VP1 C‐terminal halves of three foot‐and‐mouth disease virus (FMDV) serotypes) was constructed. In vitro transfection studies in BHK‐21 cells revealed that the construct was able to express FMDV‐specific antigen but does not overproduce the antigen. Immunization of guinea pigs with the construct at dose rate of 10, 5, 2 and 1 μg per animal through intramuscular route showed significant neutralizing antibody induction at all doses against all serotype tested as compared to non‐immunized controls. On viral challenge of guinea pigs 4 week post‐immunization with 1000 GPID50 of FMDV serotype A, it was observed that the immunization not only delayed the appearance and reduced the severity of FMD lesions significantly (P < 0.05) but also provided complete protection in several guinea pigs. In fact, two of six and one of six guinea pigs were completely protected in 10 and 5 μg immunized groups, respectively. These results suggest that the development of the replicase‐based DNA vaccine may provide a promising approach as an alternative vaccine strategy for controlling FMD.
Single Nucleotide Polymorphism in the Interleukin 12B Gene is Associated with Risk for Breast Cancer Development
Authors: Kaarvatn M. H. , Vrbanec J. , Kulic A. , Knezevic J. , Petricevic B. , Balen S. , Vrbanec D. , Dembic Z.
Published: June 2012

We analysed the association of a single nucleotide polymorphism (SNP) in the gene encoding the IL‐12 subunit p40 (IL12B, rs3212227, A>C) with breast cancer. The SNPs allelic and genotypic frequencies were compared between patients (n = 191) and healthy (n = 194) women in a case–control study from Croatia. The major allele (A) was associated with susceptibility to breast cancer (P = 0.003; OR = 1.67; 95% CI: 1.17–2.38). Likewise, the minor allele (C) was significantly correlated with protection (P = 0.003; OR = 0.60; 95% CI: 0.42–0.86). At the genotype level, AA homozygosity was significantly associated with predisposition to disease (P = 0.013; OR = 1.68, 95% CI: 1.09–2.59), whereas the minor allele homozygosity (CC) was correlated with protection to disease (P = 0.020, OR = 0.28, 95% CI: 0.09–0.91). The heterozygous genotype showed no significant correlation with disease. The product of the IL12B gene (IL‐12 p40) can either form a homodimeric cytokine or be part of two pro‐inflammatory (IL‐12 and IL‐23) cytokines. It is presently unclear whether the major allele is associated with higher or lower protein levels of IL‐12 p40 and IL‐12 p70, which are critical in inflammation and adaptive immune responses. However, as the A allele is high producer of IL12B (p40) mRNA, these results might imply that higher levels of IL‐12 p40 (either as homodimers or joined with one or both of the other two subunits) predispose to breast cancer.
Toll‐Like Receptor Gene Polymorphisms Confer Susceptibility to Graft‐Versus‐Host Disease in Allogenic Hematopoietic Stem Cell Transplantation
Authors: Sivula J. , Cordova Z. M. , Tuimala J. , Jaatinen T. , Partanen J. , Volin L. , Turpeinen H.
Published: June 2012

Graft‐versus‐host disease (GvHD) is a major complication in hematopoietic stem cell transplantation (HSCT). The immune response against gut microbes is thought to be an important factor in the beginning of GvHD. Toll‐like receptors (TLR) recognize molecular structures of microbes and viruses and play central part in the innate immunity. We studied whether genetic variation in the TLR1, TLR2, TLR4, TLR5, TLR6 and TLR10 genes confers susceptibility to GvHD in 305 human leucocyte antigen‐identical sibling donor HSCT's performed in a single Finnish centre. The results showed that the genetic markers rs4833079 (P = 0.035) in TLR1, rs4837656 (P = 0.032) and rs17582214 (P = 0.029) in TLR4, rs10737416 (P = 0.048) in TLR5, rs6531656 (P = 0.035) in TLR6, and rs337629 (P = 0.005) in TLR10 were associated with the occurrence of acute GvHD. Interestingly, two markers in the TLR5 gene, rs2800230 (P = 0.010) and rs2800237 (P = 0.017), were associated with chronic GvHD. These results indicate that many genes of the TLR system are involved in the overall genetic risk for GvHD and emphasize the role of innate immunity in GvHD.
Transcriptome Analysis of the Interferon‐Signature Defining the Autoimmune Process of Sjögren’s Syndrome
Authors: Peck A. B. , Nguyen C. Q.
Published: June 2012

Sjögren’s syndrome (SS) of humans and SS‐like (SjS‐like) diseases in mouse models are characterized by chronic immune attacks against the salivary and lacrimal glands leading to exocrine dysfunction. One characteristic of SS and SjS‐like diseases repeatedly observed is a strong upregulated expression of both the type I (α/β) and type II (γ) interferons (IFNs). In addition, recent global transcriptome studies have identified a variety of IFN‐stimulated gene (ISG) transcripts differentially expressed in tissues of SS patients and mouse models exhibiting SjS‐like disease. Analyses of these transcriptome databases indicate that the sets of differentially expressed genes are highly restricted, suggesting that there is a unique specificity in ISGs activated (or suppressed) during development and onset of disease. As a result, these observations have led to both SS and SjS‐like diseases being designated as ‘interferon‐signature’ diseases. While SS and SjS‐like diseases may be designated as such, very little effort has been made to determine what an interferon‐signature might signify relative to autoinflammation and whether it might point directly to an underlying etiopathological mechanism. Here, we review these limited data and provide a model of how the products of these genes interact molecularly and biologically to define critical details of SS pathology.
Arabidopsis thaliana CENTRORADIALIS homologue(ATC) acts systemically to inhibit floral initiation in Arabidopsis
Authors: Huang Nien‐Chen , Jane Wann‐Neng , Chen Jychian , Yu Tien‐Shin
Published: June 2012

Floral initiation is orchestrated by systemic floral activators and inhibitors. This remote‐control system may integrate environmental cues to modulate floral initiation. Recently, FLOWERING LOCUS T (FT) was found to be a florigen. However, the identity of systemic floral inhibitor or anti‐florigen remains to be elucidated. Here we show thatArabidopsis thaliana CENTRORADIALIS homologue(ATC), an ArabidopsisFThomologue, may act in a non‐cell autonomous manner to inhibit floral initiation. Analysis of theATCnull mutant revealed thatATCis a short‐day‐induced floral inhibitor. Cell type‐specific expression showed that companion cells and apex that expressATCare sufficient to inhibit floral initiation. Histochemical analysis showed that the promoter activity ofATCwas mainly found in vasculature but under the detection limit in apex, a finding that suggests thatATCmay move from the vasculature to the apex to influence flowering. Consistent with this notion, Arabidopsis seedling grafting experiments demonstrated thatATCmoved over a long distance and that floral inhibition byATCis graft transmissible. ATC probably antagonizes FT activity, because both ATC and FT interact with FD and affect the same downstream meristem identity genesAPETALA1, in an opposite manner. Thus, photoperiodic variations may trigger functionally oppositeFThomologues to systemically influence floral initiation.
Rhomboid proteins in the chloroplast envelope affect the level of allene oxide synthase in Arabidopsis thaliana
Authors: Knopf Ronit Rimon , Feder Ari , Mayer Kristin , Lin Albina , Rozenberg Mor , Schaller Andreas , Adam Zach
Published: June 2012

Rhomboids are intra‐membrane serine proteases whose sequences are found in nearly all organisms. They are involved in a variety of biological functions in both eukaryotes and prokaryotes. Localization assays revealed that two Arabidopsis thaliana rhomboid‐like proteases (AtRBL), AtRBL8 and AtRBL9, are targeted to the chloroplast. Using transgenic plants expressing epitope‐tagged AtRBL9, we localized AtRBL9 to the chloroplast inner envelope membrane, with both its N‐ and C‐termini facing the stroma. Mass spectrometry analyses confirmed this localization, and suggested that this is also the case for AtRBL8. Both are proteins of very low abundance. The results of size‐exclusion chromatography implied that AtRBL9 forms homo‐oligomers. In search of a putative function, a comparative proteomic analysis was performed on wild‐type and double‐knockout plants, lacking both AtRBL8 and AtRBL9, using the iTRAQ method. Of 180 envelope proteins, the level of only a few was either increased or decreased in the mutant line. One of the latter, allene oxide synthase, is involved in jasmonic acid biosynthesis. This observation provides an explanation for the recently reported aberration in flower morphology that is associated with the loss of AtRBL8.
New Antagonistic Strains of Non‐Pathogenic Agrobacterium vitis to Control Grapevine Crown Gall
Authors: Kawaguchi Akira , Inoue Koji
Published: June 2012

Graft unions of nursery stock of grapevine (Vitis vinifera L.) collected in Japan yielded non‐pathogenic strains of Agrobacterium. On the basis of classic diagnostic tests, a sequence analysis and a previously reported multiplex PCR method, the non‐pathogenic strains ARK‐1, ARK‐2 and ARK‐3 were identified as Agrobacterium vitis. Stems of grapevine seedlings were inoculated with both a cell suspension of seven mixed strains of A. vitis (Ti) as a pathogen and one of a new strain or A. vitis strain VAR03‐1, one of the biological control agents against crown gall previously reported, as competitors to assay the suppression of tumour formation caused by the pathogen. In a test with a 1:1 cell ratio of pathogen/nonpathogen, strains ARK‐1, ARK‐2 and ARK‐3 reduced the tumour incidence.. In particular, strain ARK‐1 was strongest at inhibiting tumour formation in this study. Strain ARK‐1 established populations on roots of grapevine tree rootstock and persisted on roots for a year. ARK‐1, ARK‐2 and ARK‐3 did not produce a halo of inhibition against A. vitis (Ti) strain on YMA medium. Moreover, strain ARK‐1 did not reduce tumour incidence on the stems of grapevine when ARK‐1 was dead or only culture filtrate was used. This result indicates the possibility that these new strains inhibit grapevine crown gall in planta by a different mechanism other than VAR03‐1. In particular, one of the new strains, named ARK‐1, was most effective in inhibiting tumour formation on grapevine and appears to be a promising new agent to control grapevine crown gall.
Cell Cycle–dependent Dynamics of Cytoskeleton Involving Mitochondrial Redistribution in Hamster Embryos
Authors: Kabashima K , Yoshinaga D , Fang J , Matsuzaki M , Suzuki H
Published: June 2012

Contents

Mitochondria–cytoskeleton interactions were studied in the hamster embryos during interphase and M phase of the cell cycle. Two‐cell embryos were cultured for 1 h with nocodazole, cytochalasin D or in a combination of both inhibitors and then centrifuged at 10 000×g for 2 min. The control embryos were only centrifuged with no inhibitor treatment. Centrifuged embryos were fluorescently stained to examine the distribution of active mitochondria and nuclear configuration. In the control 2‐cell embryos, most mitochondria were accumulated at the perinuclear region with some at the cell cortex. Neither each inhibitor nor centrifugation did affect the distribution of mitochondria in interphase blastomeres. However, mitochondria were spun down towards the centrifugal pole in 71% (n = 41) of the interphase blastomeres treated with centrifugation following a combination of nocodazole plus cytochalasin D, suggesting that both microtubules and microfilaments may involve in mitochondrial redistribution during interphase of the cell cycle. In contrast, when M‐phase blastomeres were treated with all drug treatments applied, including cytochalasin D, mitochondria had been usually dislocated in a unipolar cluster, suggesting that microfilaments, not microtubules, may involve in the mitochondrial redistribution during M phase of the cell cycle. The data indicate that microfilaments function in mitochondrial redistribution regardless of the stages of the cell cycle and that microtubules may strongly associate with mitochondria during the interphase but dissociate from them during the M phase.
Effect of nitric oxide donors S‐nitroso‐N‐acetyl‐dl‐penicillamine, spermine NONOate and propylamine propylamine NONOate on intracellular pH in cardiomyocytes
Authors: Pravdic Danijel , Vladic Nikolina , Cavar Ivan , Bosnjak Zeljko J
Published: June 2012

Previous studies suggest that exogenous nitric oxide (NO) and NO‐dependent signalling pathways modulate intracellular pH (pHi) in different cell types, but the role of NO in pHi regulation in the heart is poorly understood. Therefore, in the present study we investigated the effect of the NO donors S‐nitroso‐N‐acetyl‐dl‐penicillamine, spermine NONOate and propylamine propylamine NONOate on pHi in rat isolated ventricular myocytes.

Cells were isolated from the hearts of adult Wistar rats and pHi was monitored using the pH‐sensitive fluorescent indicator 5‐(and‐6)‐carboxy seminaphtharhodafluor (SNARF)‐1 (10 μmol/L) and a confocal microscope. To test the effect of NO donors on the Na+/H+ exchanger (NHE), basal pHi in Na+‐free buffer and pHi recovery from intracellular acidosis after an ammonium chloride (10 mmol/L) prepulse were monitored. The role of carbonic anhydrase was tested using acetazolamide (50 μmol/L). 4,4‐Diisothiocyanatostilbene‐2,2′‐disulphonic acid (0.5 mmol/L; DIDS) was used to inhibit the Cl−/OH− and Cl−/exchangers. Acetazolamide and DIDS were applied via the superfusion system 1 and 5 min before the NO donors.

All three NO donors acutely decreased pHi and this effect persisted until the NO donor was removed. In Na+‐free buffer, the decrease in basal pHi was increased, whereas inhibition of carbonic anhydrase and Cl−/OH− and Cl−/ exchangers did not alter the effects of the NO donors on pHi. After an ammonium preload, pHi recovery was accelerated in the presence of the NO donors.

In conclusion, exogenous NO decreases basal pHi, leading to increased NHE activity. Carbonic anhydrase and chloride‐dependent sarcolemmal and OH− transporters are not involved in the NO‐induced decrease in pHi in rat isolated ventricular myocytes.
Suspected macular degeneration in a captive western lowland gorilla (gorilla gorilla gorilla)
Authors: Steinmetz Andrea , Bernhard Andreas , Sahr Sabine , Oechtering Gerhard
Published: June 2012

The case of a 31‐year‐old captive female Western lowland gorilla (Gorilla gorilla gorilla) with decreased near vision but good distance vision is presented. Examination of the fundus revealed drusen‐like bodies in the macula presumably because of an age‐related macular degeneration (AMD).
Abundant immunoglobulin E‐positive cells in skin lesions support an allergic etiology of atopic dermatitis in the elderly
Authors: Tanei R. , Hasegawa Y. , Sawabe M.
Published: June 2012

Background/Objectives  Atopic dermatitis (AD) in the elderly is gradually increasing in industrialized countries in association with the aging of society. We report herein four cases of elderly AD {three extrinsic [immunoglobulin (Ig)E‐mediated allergy]; one intrinsic (non‐IgE‐allergy)} in which we investigated the presence of IgE+ cells in lesional skin.

Methods/Results  Single immunohistochemical and double immunofluorescence stainings were performed for skin biopsy specimens from AD patients and non‐atopic control subjects with chronic eczema. In the lesional lichenified skin of patients with extrinsic elderly AD, numerous IgE+ cells were found among inflammatory cells infiltrates in the upper dermis. Comparative analysis of single immunohistochemistry results using serial paraffin and/or frozen sections found that many IgE+ cells showed identical distributions to tryptase+ mast cells. IgE+ cells coincident with CD1a+ Langerhans cells in the epidermis were found in small numbers only in frozen sections. Double immunofluorescence staining for IgE and CD11c revealed cells coexpressing IgE and CD11c with a dendritic morphology in the papillary and upper dermis. These IgE+ mast cells and IgE+ CD11c+ cells were also found in cured normal‐looking skin from a patient with extrinsic elderly AD after successful treatment. Although only a few weakly positive IgE+ cells were detected, no IgE+CD11c+ cells were found in specimens from patients with intrinsic elderly AD or non‐atopic chronic eczema.

Conclusion  IgE‐mediated allergic inflammation may play an important role in the pathobiology of elderly AD, similar to other age groups of AD.
Evaluation and cross‐cultural adaptation of the Hendrich II Fall Risk Model to Portuguese
Authors: Caldevilla Mª Nilza , Costa Mª Arminda M. , Teles Paulo , Ferreira Pedro M.
Published: June 2012

Scand J Caring Sci; 2013; 27; 468–474

Evaluation and cross‐cultural adaptation of the Hendrich II Fall Risk Model to Portuguese

Background:  Several tools for the assessment of the risk of falling are used commonly by clinical nurses, but none have been validated in Portuguese.

Aims:  To adapt and evaluate the Hendrich II Fall Risk Model (HIIFRM) for use with elderly Portuguese inpatients.

Method:  We conducted a prospective study of 586 older inpatients in acute care hospitals, from November 2007 to May 2010.

Results:  The study involved 270 men and 316 women. The most frequent risk factor on admission and at discharge was a score ≥3 on the ‘Get Up and Go’ test. The adapted HIIFRM showed a sensitivity of 93.2% and 75.7%, and a specificity of 35% and 46.7%, on admission and at discharge, respectively. A positive predictive value of 17.2% on admission and 17% at discharge and a negative predictive value of 97.3% and 93%, respectively, were estimated.

Conclusions:  The HIIFRM was shown to be a useful tool in predicting falls by patients. Nevertheless, the research model suggested that only four risk factors affected the occurrence of falls significantly on admission and two risk factors at discharge. Further research is required in Portuguese hospital settings.
High tryptophan diet reduces CA1 intraneuronal β‐amyloid in the triple transgenic mouse model of Alzheimer’s disease
Authors: Noristani Harun N. , Verkhratsky Alexei , Rodríguez José J.
Published: June 2012

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that impairs mnesic functions. The histopathology of the disease is manifested by the accumulation of intracellular β‐amyloid (Aβ) and subsequent formation of neuritic plaques as well as the presence neurofibrillary tangles in specific brain regions associated with learning and memory including the hippocampus. Here, we analysed the effect of chronic (1 month) food diets containing low (LTrP), normal (NTrP) and high tryptophan (HTrP), 0.04, 0.20 and 0.40 g/100 g, respectively, on CA1 serotonin transporter (SERT) fibre density, intraneuronal Aβ deposition and total number of serotonergic (5‐HT) neurons in an AD triple transgenic (3xTg‐AD) mouse model. Nontransgenic (non‐Tg) animals fed with HTrP displayed increased SERT fibre density in CA1 (35%) and in stratum lacunosum moleculare (S.Mol) (48%) compared to LTrP diet. Transgenic animals showed increased SERT fibre density in CA1 S.Mol compared to diet‐matched non‐Tg irrespective of dietary tryptophan content (104% for LTrP, 74% for NTrP and 35% for HTrP); no differences were observed in the total number of 5‐HT neurons neither in the dorsal nor in the median raphe nuclei. However, and more relevant to AD, HTrP diet reduced intraneuronal Aβ density (by a 17%) in transgenic animals compared to transgenic animals fed with NTrP diet. Our results show that increased dietary TrP intake reduces intraneuronal Aβ load in the 3xTg‐AD mouse model of AD, suggesting that enhanced TrP intake and in consequence a potential increase in 5‐HT neurotransmission may be effective in reducing plaque pathology in AD.
Deviation of innate circadian period from 24 h reduces longevity in mice
Authors: Libert Sergiy , Bonkowski Michael S. , Pointer Kelli , Pletcher Scott D. , Guarente Leonard
Published: June 2012

The variation of individual life spans, even in highly inbred cohorts of animals and under strictly controlled environmental conditions, is substantial and not well understood. This variation in part could be due to epigenetic variation, which later affects the animal’s physiology and ultimately longevity. Identification of the physiological properties that impact health and life span is crucial for longevity research and the development of anti‐aging therapies. Here, we measured individual circadian and metabolic characteristics in a cohort of inbred F1 hybrid mice and correlated these parameters to their life spans. We found that mice with innate circadian periods close to 24 h (revealed during 30 days of housing in total darkness) enjoyed nearly 20% longer life spans than their littermates, which had shorter or longer innate circadian periods. These findings show that maintenance of a 24‐h intrinsic circadian period is a positive predictor of longevity. Our data suggest that circadian period may be used to predict individual longevity and that processes that control innate circadian period affect aging.
Recovery of Function Following a Hip Fracture in Geriatric Ambulatory Persons Living in Nursing Homes: Prospective Cohort Study
Authors: Beaupre Lauren A. , Jones C. Allyson , Johnston D. William C. , Wilson Donna M. , Majumdar Sumit R.
Published: June 2012

Objectives

To measure 1‐year post‐hip fracture functional recovery, health‐related quality of life (HRQL), and mortality in nursing home residents.

Design

Prospective longitudinal cohort study.

Setting and Participants

Ambulatory nursing home residents with or without impaired cognition consecutively admitted with hip fracture to three Canadian tertiary‐care hospitals from March 2008 through November 2009.

Measurements

Participants or proxy respondents completed the Functional Independence Measure Motor score (FIMmotor) and EuroQol5D index score (EQ‐5Dindex) in the hospital (prefracture status) and 3, 6, and 12 months after fracture. Complications over the first postfracture year were also ascertained; the primary outcome was functional recovery (change in FIMmotor score).

Results

Of 92 eligible participants, 60 (64%) were enrolled. The mean age was 86.9 ± 8.1, 42 (70%) were female, and 45 (75%) had three or more comorbidities. Forty‐three (72%) walked independently with or without aids before fracture. By 12 months, 27 (45%) participants had died, and 10 (17%) had withdrawn. Of the remaining 23 participants, functional status according to FIMmotor score dropped substantially and significantly after the fracture (3 months, 34.0 ± 19.7; 6 months, 33.2 ± 19.7; 12 months, 32.0 ± 20.0; P < .001 from a baseline FIMmotor score of 50.1 ± 16.1). By 12 months after the fracture, only eight (35%) were walking independently, and 11 (48%) were no longer ambulatory. HRQL according to the EQ‐5Dindex also decreased significantly (P = .003), from 0.62 ± 0.20 before fracture to 0.42 ± 0.30 by 12 months after fracture.

Conclusion

Hip fracture for nursing home residents was associated with substantial loss of functional independence, ambulation, and HRQL. Little recovery was evident after the first 3 months; there was almost 50% mortality within 12 months.
Fatigability in Basic Indoor Mobility in Nonagenarians
Authors: Mänty Minna , Ekmann Anette , Thinggaard Mikael , Christensen Kaare , Avlund Kirsten
Published: June 2012

Objectives

To evaluate the prevalence and associated health factors of indoor mobility–related fatigability in nonagenarians.

Design

A cross‐sectional observational study of all Danes born in 1905 and assessed in 1998.

Setting

Community, sheltered housing and nursing homes.

Participants

Individuals aged 92 and 93 (N = 1,181) who were independent of help in basic indoor mobility.

Measurements

Fatigability in basic indoor mobility was defined as a subjective feeling of fatigue when transferring or walking indoors. Other standardized assessments include self‐report measures of medical history and performance‐based assessments of walking speed and maximum handgrip strength.

Results

Twenty‐six percent of participants reported fatigability when transferring or walking indoors; fatigability was more common in participants living in sheltered housing (32%) than in those living independently (23%, P < .001). Cardiovascular diseases, musculoskeletal pain, medications, walking speed, and depressive symptoms were independently associated with fatigability.

Conclusion

Fatigability in basic everyday mobility is common in nondisabled nonagenarians. The results also indicate important associations between fatigability and potentially modifiable health factors.
Use of an Online Curriculum to Teach Delirium to Fourth‐Year Medical Students: A Comparison with Lecture Format
Authors: Chao Serena H. , Brett Belle , Wiecha John M. , Norton Lisa E. , Levine Sharon A.
Published: June 2012

Web‐based learning methods are being used increasingly to teach core curriculum in medical school clerkships, but few studies have compared the effectiveness of online methods with that of live lectures in teaching the same topics to students. Boston University School of Medicine has implemented an online, case‐based, interactive curriculum using videos and text to teach delirium to fourth‐year medical students during their required 1‐month Geriatrics and Home Medical Care clerkship. A control group of 56 students who received a 1‐hour live delirium lecture only was compared with 111 intervention group students who completed the online delirium curriculum only. Evaluation consisted of a short‐answer test with two cases given as a pre‐ and posttest to both groups. The total possible maximum test score was 34 points, and the lowest possible score was −8 points. Mean pre‐ and posttest scores were 10.5 ± 4.0 and 12.7 ± 4.4, respectively, in the intervention group and 9.9 ± 3.5 and 11.2 ± 4.5, respectively, in the control group. The intervention group had statistically significant improvement between the pre‐ and posttest scores (2.21‐point difference; P < .001), as did the control group (1.36‐point difference; P = .03); the difference in test score improvement between the two groups was not statistically significant. An interactive case‐based online curriculum in delirium is as effective as a live lecture in teaching delirium, although neither of these educational methods alone produces robust increases in knowledge.
Discrepancy Between Self‐ and Proxy‐Rated Pain in Alzheimer's Disease: Results from the Danish Alzheimer Intervention Study
Authors: Jensen‐Dahm Christina , Vogel Asmus , Waldorff Frans B. , Waldemar Gunhild
Published: June 2012

Objectives

To investigate the prevalence of self‐ and proxy‐reported pain in a cohort with Alzheimer's disease (AD) and to identify characteristics of individuals with AD reporting pain.

Design

Data were collected at the baseline visit of the Danish Alzheimer Intervention Study.

Setting

Community.

Participants

Three hundred twenty‐one community‐living individuals with AD (MMSE ≥ 20) and their primary caregivers.

Measurements

Pain was assessed as part of the EuroQol EQ‐5D (caregiver‐ and self‐rated). The Cornell Scale for Depression in Dementia, Quality of Life in Alzheimer's Disease Scale, EQ‐5D visual analog scale, Mini‐Mental State Examination, and Neuropsychiatric Inventory Questionnaire were also used.

Results

Fair agreement was found between self‐ and proxy ratings on pain (kappa = 0.34). Thirty‐three percent of individuals with AD reported pain, whereas caregivers reported that 52% had pain (
P
 < .001). Individuals who had self‐ or proxy‐rated pain were significantly more likely to be female, had more depressive and other neuropsychiatric symptoms, and rated their quality of life lower.

Conclusion

Self‐ and proxy‐reported pain differ in individuals with mild AD, with proxies rating more pain than the individuals with AD. Self‐ and proxy‐rated pain was significantly associated with more neuropsychiatric and depressive symptoms and lower quality of life. In general, this study indicates that pain occurs frequently even in individuals with mild AD and that pain assessment may require self‐ and proxy report to identify individuals with need for possible treatment.
Ethnic Disparities in Adherence to Antihypertensive Medications of Medicare Part D Beneficiaries
Authors: Holmes Holly M. , Luo Ruili , Hanlon Joseph T. , Elting Linda S. , Suarez‐Almazor Maria , Goodwin James S.
Published: June 2012

Objectives

To determine the level of adherence to medications and characteristics of Part D beneficiaries associated with higher levels of antihypertensive medication adherence.

Design

Retrospective cohort study.

Setting

Medicare claims and Part D event files.

Participants

Medicare Part D enrollees with prevalent uncomplicated hypertension who filled at least one antihypertensive prescription in 2006 and two prescriptions in 2007.

Measurements

Medication adherence was defined as an average medication possession ratio of 80% or greater. Potential factors associated with adherence evaluated were age, sex, race or ethnicity, socioeconomic factors, comorbidity, medication use, copayments, being in the coverage gap, and number of unique prescribers.

Results

Overall adherence was 79.5% of 168,522 Medicare Part D enrollees with prevalent uncomplicated hypertension receiving antihypertensive medicines in 2007. In univariate analysis, adherence varied significantly according to most patient factors. In multivariable analysis, lower odds of adherence persisted for blacks (odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.51–0.55), Hispanics (OR = 0.58, 95% CI = 0.55–0.61), and other non‐white races (OR = 0.80 95% CI = 0.75–0.85) than for whites. Greater comorbidity and concurrent medication use were also associated with poorer adherence. Adherence was significantly different across several geographic regions.

Conclusion

A number of associations were identified between patient factors and adherence to antihypertensive drugs, with significant differences in adherence according to ethnicity. Improving adherence could have significant public health implications and could improve outcomes specific to hypertension, as well as improving cost and healthcare utilization.
Association Between Mobility, Participation, and Wheelchair‐Related Factors in Long‐Term Care Residents Who Use Wheelchairs as Their Primary Means of Mobility
Authors: Mortenson W. Ben , Miller William C. , Backman Catherine L. , Oliffe John L.
Published: June 2012

Objectives

To explore how wheelchair‐related factors, mobility, and participation are associated in a sample of long‐term care residents who use wheelchairs as their primary means of mobility.

Design

Cross‐sectional survey.

Setting

Eleven residential care facilities in the lower mainland of British Columbia, Canada.

Participants

One hundred forty‐six self‐responding residents and 118 proxy respondents: mean age 84 (range 60–103). Most were female (69%), and a small proportion (9%) drove a power wheelchair.

Measurements

The Nursing Home Life Space Diameter Assessment was used to measure resident mobility, and the Late Life Function and Disability Instrument: Disability Component was used to measure participation frequency in daily activities.

Results

Path analysis indicated that wheelchair‐related factors were associated with participation frequency directly and indirectly through their relationship with mobility. The final model explained 46% of the variance in resident mobility and 53% of the variance in resident participation frequency. Wheelchair skills, which include the ability to transfer in and out of and propel a wheelchair, were important predictors of life‐space mobility and frequency of participation, and life space mobility was a significant predictor of frequency of participation. Depression was associated with poorer wheelchair skills and mobility and less‐frequent participation. Counterintuitively, perceived environmental barriers were positively associated with frequency of participation.

Conclusion

The findings suggest that, by addressing wheelchair‐related factors, resident's mobility and participation may be improved, but the efficacy of this approach needs to be confirmed experimentally.
Environmental Determinants of Quality of Life in Nursing Home Residents with Severe Dementia
Authors: Garre‐Olmo Josep , López‐Pousa Secundino , Turon‐Estrada Antoni , Juvinyà Dolors , Ballester David , Vilalta‐Franch Joan
Published: June 2012

Objectives

To determine the relationship between quality of life (QOL) and environmental factors of temperature, noise, and lighting in nursing home residents with severe dementia.

Design

Cross‐sectional, observational, analytical.

Setting

Eight public, long‐term care nursing homes in the province of Girona, Spain.

Participants

Random sample of 160 nursing home residents with severe dementia.

Measurements

Functional and cognitive impairment, pain, neuropsychiatric disturbances, and QOL were determined using standardized instruments. Temperature, noise, and lighting in bedrooms, dining rooms, and living rooms were measured in the morning and afternoon using a multifunction environment meter in a standardized manner.

Results

Adjusted multivariate linear regression models demonstrated that environmental measures were independently associated with QOL and related factors. High temperature in the bedroom was associated with lower QOL (standardized β = 0.184), high noise levels in the living room were associated with low behavioral signs of social interactions (β = 0.196), and low lighting levels in the bedroom were associated with number of signs of negative affective mood (β = −0.135).

Conclusion

The QOL of nursing home residents with severe dementia was related to environmental factors such as temperature, noise, and lighting. The monitoring of these environmental factors may improve these individuals' QOL.
Glycosylated Hemoglobin and Functional Decline in Community‐Dwelling Nursing Home–Eligible Elderly Adults with Diabetes Mellitus
Authors: Yau Celia K. , Eng Catherine , Cenzer Irena Stijacic , John Boscardin W. , Rice‐Trumble Kathy , Lee Sei J.
Published: June 2012

Objectives

To determine whether glycosylated hemoglobin (HbA1c) levels predict functional decline in older adults.

Design

Longitudinal cohort study.

Participants

Community‐dwelling, nursing home (NH)‐eligible individuals with diabetes mellitus enrolled at On Lok between October 2002 and December 2008 (367 participants, 1,579 HbA1c measurements).

Setting

On Lok Lifeways, the original model for Programs of All‐Inclusive Care for the Elderly.

Measurements

The outcomes were functional decline or death at 2 years. The primary predictor was HbA1c. Age, sex, race and ethnicity, baseline function, comorbid conditions, length of time enrolled at On Lok, insulin use, and clustering of HbA1c within participants were adjusted for with mixed‐effects Poisson regression.

Results

Mean age was 80, and 185 participants (50%) were taking insulin. Sixty‐three percent of participants experienced functional decline, and 75% experienced death or functional decline during the study period. At 2 years, higher HbA1c was associated with less functional decline or death (P for trend = .006). Accounting for clustering and confounding factors, HbA1c of 8.0% to 8.9% was associated with a lower likelihood (relative risk = 0.88, 95% confidence interval = 0.79–0.99) of functional decline or death than HbA1c of 7.0% to 7.9%.

Conclusion

In community‐dwelling, NH‐eligible individuals with diabetes mellitus, HbA1c of 8.0% to 8.9% is associated with better functional outcomes at 2 years than HbA1c of 7.0% to 7.9%, suggesting that the current American Geriatrics Society guideline recommending a HbA1c target of 8.0% or less for older adults with limited life expectancy may be lower than necessary to maintain function.
Kidney Function and Cognitive and Functional Decline in Elderly Adults: Findings from the Singapore Longitudinal Aging Study
Authors: Feng Liang , Yap Keng Bee , Yeoh Lee Ying , Ng Tze Pin
Published: June 2012

Objectives

To investigate whether lower estimated glomerular filtration rate (eGFR) or chronic kidney disease (CKD) was associated with subsequent cognitive and instrumental activity of daily living (IADL) decline in a prospective cohort study.

Design

Prospective cohort study, followed for up to 4 years.

Setting

General community.

Participants

One thousand three hundred fifteen adults aged 55 and older from the Singapore Longitudinal Aging Study.

Measurements

Baseline data included eGFR levels, presence of CKD (eGFR < 60 mL/min per 1.73 m2), and known confounders. Cognitive decline was defined as a drop of 2 or more points on the Mini‐Mental State Examination (MMSE) and functional decline as a drop of 2 or more points in IADL score.

Results

Decreasing levels of eGFR and the presence of CKD were associated with greater odds of cognitive decline at follow‐up independent of confounding risk factors in multivariate analyses: estimated 14% increment in odds of cognitive decline per 10 mL/min/1.73 m2 decrease in eGFR (odds ratio = 1.94, 95% confidence interval = 1.23–3.05; P = .004 for CKD vs non‐CKD). Similar associations were found in a cognitively normal subgroup (MMSE > 23) at baseline. In the whole sample, CKD, but not eGFR, was found to be significantly associated with higher risk of IADL decline.

Conclusion

CKD in older persons was significantly associated with cognitive and functional decline. Future research should target the development and evaluation of strategies to delay or prevent cognitive decline and physical disability in elderly adults with impaired kidney function.
Objectively Measured Sleep Quality and Nursing Home Placement in Older Women
Authors: Spira Adam P. , Covinsky Kenneth , Rebok George W. , Stone Katie L. , Redline Susan , Yaffe Kristine
Published: June 2012

Objectives

To determine the association between objectively measured sleep and subsequent placement in a nursing home or a personal care home.

Design

Prospective cohort.

Setting

Participants' homes and sites of the Study of Osteoporotic Fractures.

Participants

One thousand six hundred sixty‐four community‐dwelling women with a mean age of 83 ± 4.

Measurements

At baseline, participants completed an average of 4 nights of wrist actigraphy; they provided data on place of residence at baseline and at follow‐up, 5 years later.

Results

At baseline, participants had a mean total sleep time of 408 ± 72 minutes, mean wake after sleep onset of 71 ± 43 minutes, and mean sleep efficiency of 79 ± 11%. At follow‐up, 71 (4%) were residing in a nursing home, and 127 (8%) were in a personal care home. Women with the most wake after sleep onset (by quartile) had more than twice the odds as those with the least of placement in a nursing home (adjusted odds ratio (AOR) = 2.94, 95% confidence interval (CI) = 1.34–6.44) or a personal care home (AOR = 2.33, 95% CI = 1.26–4.30). Similarly, women with the lowest sleep efficiency had more than three times the odds as those with the highest of nursing home placement (AOR = 3.25, 95% CI = 1.35, 7.82) and more than twice the odds of placement in a personal care home (AOR = 2.38, 95% CI = 1.33, 4.24). There was no association between sleep duration and placement.

Conclusion

In very old community‐dwelling women, greater wake after sleep onset and lower sleep efficiency are risk factors for placement in a nursing home or personal care home. Sleep duration alone does not appear to increase the risk of placement in these long‐term care settings.
The response of cortical alpha activity to pain and neuromuscular changes caused by exercise‐induced muscle damage
Authors: Plattner K. , Lambert M. I. , Tam N. , Baumeister J.
Published: June 2012

Exercise‐induced muscle damage (EIMD) is characterized by pain, swelling, and shortening of the muscle; increased serum creatine kinase; decreased force output; and altered neuromuscular function. The aim of this study was to investigate the effects of EIMD to determine the relationship between the peripheral symptoms, neuromuscular changes, and delayed pain sensation during a submaximal movement of the biceps brachii on cortical alpha (α) activity. In contrast to the control (n = 12) group, the experimental (n = 16) group participated in an EIMD protocol, and both groups were monitored for 132 h post‐EIMD protocol. At 12 h, neuromuscular functioning was already disturbed while the sensation of pain was perceived, but not fully developed. Muscle pain scores in the experimental group peaked after 36 h with the lowest torque reported at 12 h. α‐1 activity increased significantly in the motor and somatosensory area 12 h post‐EIMD while α‐2 activity increased in the contralateral fronto‐central area. At 36 h, pain had further increased and neuromuscular function improved while α‐1 and α‐2 activities had decreased. We hypothesize that α‐1 activity over the motor and somatosensory cortex of the experimental group displays a compensatory increase in response to the changes in neuromuscular function during movement, while an increase in α‐2 activity is related to the suppression of pain experienced within the first 12 h.
Stimulation of bone formation in the expanding premaxillary suture with a GSK‐3β inhibitor
Authors: Jiang Y , Liu HX , Guo JJ , Tang GH , Qian YF
Published: June 2012

Oral Diseases (2012) 19, 73–79

Objectives:  Glycogen synthase kinase‐3β (GSK‐3β)/β‐catenin signaling mediates osteogenesis in response to mechanical loading. We tested the hypothesis that local administration of a GSK‐3β inhibitor could stimulate new bone formation in the expanding premaxillary suture.

Materials and methods:  Thirty‐five Sprague–Dawley rats were subjected to premaxillary suture expansion using a helix spring. The experimental rats were given one or two local injections of SB‐415286, a small‐molecule GSK‐3β inhibitor. Animals were administered calcein and sacrificed on day 7 to quantify new bone formation. To evaluate the proliferation and differentiation of osteoblasts, rats were labeled with bromodeoxyuridine on day 1 and sacrificed on day 2 or 4. β‐catenin expression was evaluated by immunohistochemical staining.

Results:  Two injections of SB‐415286 led to an elevation of β‐catenin expression and an increase in the number of proliferating osteoblasts in expanding sutures on day 2 and day 4. Consequently, new bone formation in the suture increased significantly on day 7.

Conclusions:  These results suggest that local delivery of a GSK‐3β inhibitor could stimulate bone formation in the expanding premaxillary suture by eliciting β‐catenin signaling. GSK‐3β could be a pharmaceutical target for improving the effect of orthodontic treatments such as rapid palatal expansion.
Transnationalism and Development: Mexican and Chinese Immigrant Organizations in the United States
Authors: Portes Alejandro , Zhou Min
Published: June 2012

The literature on development in economics and sociology has tended to focus on capital flows, investments, and, more recently, institutions as key causal factors. International migration, when discussed, is relegated to the status of a symptom of underdevelopment and even a factor contributing to it. The more recent literature on migrant remittances has partially reversed this view by documenting large hard currency transfers made by expatriates to their home countries. This changed approach to migration and development does not go far enough because it does not take into account the organized efforts of immigrant communities themselves. Nor does it consider important developmental synergies produced by the rising interactions between immigrant organizations and sending‐country governments. Using data from a recently completed comparative study, we document these processes for two major countries of out‐migration—Mexico and China. The study compiled inventories of migrant organizations from both countries in the United States, interviewed leaders of the major ones, and complemented these data with interviews with officials and community leaders in each sending country. Profiles of these transnational ties were constructed, exemplifying their increasing density and developmental impact at the local and national levels. Theoretical and policy implications of the findings are discussed.
Identification of FDA‐approved Drugs that Computationally Bind to MDM2
Authors: Warner Wayne A. , Sanchez Ricardo , Dawoodian Alex , Li Esther , Momand Jamil
Published: June 2012

The integrity of the p53 tumor suppressor pathway is compromised in the majority of cancers. In 7% of cancers p53 is inactivated by abnormally high levels of MDM2 – an E3 ubiquitin ligase that polyubiquitinates p53, marking it for degradation. MDM2 engages p53 through its hydrophobic cleft, and blockage of that cleft by small molecules can re‐establish p53 activity. Small molecule MDM2 inhibitors have been developed, but there is likely to be a high cost and long time period before effective drugs reach the market. An alternative is to repurpose FDA‐approved drugs. This report describes a new approach, called Computational Conformer Selection, to screen for compounds that potentially inhibit MDM2. This screen was used to computationally generate up to 600 conformers of 3244 FDA‐approved drugs. Drug conformer similarities to 41 computationally‐generated conformers of MDM2 inhibitor nutlin 3a were ranked by shape and charge distribution. Quantification of similarities by Tanimoto combo scoring resulted in scores that ranged from 0.142 to 0.802. In silico docking of drugs to MDM2 was used to calculate binding energies and to visualize contacts between the top‐ranking drugs and the MDM2 hydrophobic cleft. We present 15 FDA‐approved drugs predicted to inhibit p53/MDM2 interaction.