bluuebunny/crossref_metadata_2025 huggingface dataset:
Teacher’s Perceptions of Technology Use in the Schools
Authors: Mundy Marie-Anne , Kupczynski Lori , Kee Rick
Published: March 2012

Although many schools are equipped with the latest instructional technologies, multiple studies have indicated that more than half of the teachers equipped with computers only use them for administrative functions, and only half of their students report using technology more than once a week. Many faculty members lack the technological proficiency needed to take advantage of these new technologies, making them unable to bring these technologies into the classroom and leading to many standing unused in the classroom. This study analyzes teachers’ perceptions of technology use in the classroom by surveying those who participated in the TeachUp! technology empowerment program created and developed by Digital Opportunity Trust USA, Inc. (DOT USA). The results show that teachers who were part of DOT USA’s TeachUp! program perceived a significant increase in the areas of student engagement, student excitement, student acceleration of learning, and student proficiency with computer technology. The analysis has indicated that faculty members need not only to learn how to use technology at a basic level but also to learn how to integrate that technology into their curricula. In addition, newer teachers from digital native generations must be taught how their acquired skills can be used to integrate technology into the classroom curriculum to provide complex cognitive engagement for their students. It is essential that the role of the teacher as a professional in the classroom not be discounted when evaluating classroom curriculum development and strategy, including those that would integrate various technologies.
Phylogenetic comparison of exonic US4, US7 and UL44 regions of clinical herpes simplex virus type 1 isolates showed lack of association between their anatomic sites of infection and genotypic/sub genotypic classification
Authors: Harishankar Anusha , Jambulingam Malathi , Gowrishankar Raajaram , Venkatachalam Annapoorni , Vetrivel Umashankar , Ravichandran Sathyabaarathi , Yesupadam Samson Moses , Madhavan Hajib Narahari Rao
Published: March 2012

Background

HSV-1 genome is a mosaic of recombinants. Clinical Herpes simplex virus -1 (HSV1) isolates were already genotyped as A, B and C types based on nucleotide variations at Unique Short (US) 4 (gG) and US 7 (gI) regions through phylogeny. Analysis of Glycoprotein C (gC) exon present on the Unique Long (UL) region had also revealed the existence of different genotypes. Glycoprotein C is mainly involved in initial viral attachment to heparan sulphate on host cell surface facilitating the virus's binding and penetration into cell. As the amount of heparan sulphate on the host cell surface varies according to the cell type, it is plausible that different genotypes bind differentially to cell types. Hence, this study was framed to determine the existence of novel genotypes/sub genotypes in the US or UL regions which could associate with clinical entities.

Results

All the twenty five isolates analyzed in this study were of genotype A as per their gG gene sequences. In case of gI gene, 16 out of 25 were found to be type A and the remaining nine were type B putative intergenic recombinants. Intragenic recombinations were also encountered in both the US genes, with gG possessing novel subgenotypes, arbitrarily designated A1 and A2. The 9 type B isolates of gI genes also branched out into 2 clades due to genetic variations. Glycoprotein C of UL region had two distinct genotypic clades α and β, whose topological distribution was significantly different from that of the US region. Neither the US nor UL regions, however, showed any preference among the genotypes to a specific anatomic site of infection. Even the non synonymous variations identified in the functional domain of gC, were not confined to a particular genotype/clinical entity.

Conclusion

The analyses of the US and UL regions of the HSV-1 genome showed the existence of variegated genotypes in these two regions. In contrary to the documented literature, in which Asian strains were concluded as more conserved than European ones, our study showed the existence of a higher degree of variability among Indian strains. However, the identified novel genotypes and subgenotypes were not found associated with clinical entities.
Inclusion of a specific T cell epitope increases the protection conferred against foot-and-mouth disease virus in pigs by a linear peptide containing an immunodominant B cell site
Authors: Cubillos Carolina , de la Torre Beatriz G , Bárcena Juan , Andreu David , Sobrino Francisco , Blanco Esther
Published: March 2012

Background

Foot-and-mouth disease virus (FMDV) causes an economically important and highly contagious disease of cloven-hoofed animals. FMD control in endemic regions is implemented using chemically inactivated whole-virus vaccines. Currently, efforts are directed to the development of safe and marked vaccines. We have previously reported solid protection against FMDV conferred by branched structures (dendrimeric peptides) harbouring virus-specific B and T-cell epitopes. In order to gain insights into the factors determining a protective immune response against FMDV, in this report we sought to dissect the immunogenicity conferred by different peptide-based immunogens. Thus, we have assessed the immune response and protection elicited in pigs by linear peptides harbouring the same FMDV B-cell or B and T-cell epitopes (B and TB peptides, respectively).

Results

Pigs were twice immunized with either the B-cell epitope (site A) peptide or with TB, a peptide where the B-cell epitope was in tandem with the T-cell epitope [3A (21-35)]. Both, B and TB peptides were able to induce specific humoral (including neutralizing antibodies) and cellular immune responses against FMDV, but did not afford full protection in pigs. The data obtained showed that the T-cell epitope used is capable to induce efficient T-cell priming that contributes to improve the protection against FMDV. However, the IgA titres and IFNγ release elicited by these linear peptides were lower than those detected previously with the dendrimeric peptides.

Conclusions

We conclude that the incorporation of a FMDV specific T-cell epitope in the peptide formulation allows a significant reduction in virus excretion and clinical score after challenge. However, the linear TB peptide did not afford full protection in challenged pigs, as that previously reported using the dendrimeric construction indicating that, besides the inclusion of an adecuate T-cell epitope in the formulation, an efficient presentation of the B-cell epitope is crucial to elicit full protection by peptide vaccines.
Evolution of African cassava mosaic virus by recombination between bipartite and monopartite begomoviruses
Authors: Tiendrébéogo Fidèle , Lefeuvre Pierre , Hoareau Murielle , Harimalala Mireille A , De Bruyn Alexandre , Villemot Julie , Traoré Valentin SE , Konaté Gnissa , Traoré Alfred S , Barro Nicolas , Reynaud Bernard , Traoré Oumar , Lett Jean-Michel
Published: March 2012

Background

Cassava mosaic disease (CMD) is a major constraint on cassava cultivation in Africa. The disease is endemic and is caused by seven distinct cassava mosaic geminiviruses (CMGs), some of them including several variants.

Findings

From cassava leaf samples presenting CMD symptoms collected in Burkina Faso, four DNA-A begomovirus components were cloned and sequenced, showing 99.9% nucleotide identity among them. These isolates are most closely related to African cassava mosaic virus (ACMV) but share less than 89% nucleotide identity (taxonomic threshold) with any previously described begomovirus. A DNA-B genomic component, sharing 93% nucleotide identity with DNA-B of ACMV, was also characterized. Since all genomic components have a typical genome organization of Old World bipartite begomoviruses, this new species was provisionally named African cassava mosaic Burkina Faso virus (ACMBFV). Recombination analysis of the new virus demonstrated an interspecies recombinant origin, with major parents related to West African isolates of ACMV, and minor parents related to Tomato leaf curl Cameroon virus and Cotton leaf curl Gezira virus.

Conclusion

This is the first report of an ACMV-like recombinant begomovirus arisen by interspecific recombination between bipartite and monopartite African begomoviruses.
Expression of genes involved in hepatic carnitine synthesis and uptake in dairy cows in the transition period and at different stages of lactation
Authors: Schlegel Gloria , Keller Janine , Hirche Frank , Geißler Stefanie , Schwarz Frieder J , Ringseis Robert , Stangl Gabriele I , Eder Klaus
Published: March 2012

Background

In rodents and pigs, it has shown that carnitine synthesis and uptake of carnitine into cells are regulated by peroxisome proliferator-activated receptor α (PPARA), a transcription factor which is physiologically activated during fasting or energy deprivation. Dairy cows are typically in a negative energy balance during early lactation. We investigated the hypothesis that genes of carnitine synthesis and uptake in dairy cows are enhanced during early lactation.

Results

mRNA abundances of PPARA and some of its classical target genes and genes involved in carnitine biosynthesis [trimethyllysine dioxygenase (TMLHE), 4-N-trimethylaminobutyraldehyde dehydrogenase (ALDH9A1), γ-butyrobetaine dioxygenase (BBOX1)] and uptake of carnitine [novel organic cation transporter 2 (SLC22A5)] as well as carnitine concentrations in liver biopsy samples of 20 dairy cows in late pregnancy (3 wk prepartum) and early lactation (1 wk, 5 wk, 14 wk postpartum) were determined. From 3 wk prepartum to 1 wk postpartum, mRNA abundances of PPARΑ and several PPARΑ target genes involved in fatty acid uptake, fatty acid oxidation and ketogenesis in the liver were strongly increased. Simultaneously, mRNA abundances of enzymes of carnitine synthesis (TMLHE: 10-fold; ALDH9A1: 6-fold; BBOX1: 1.8-fold) and carnitine uptake (SLC22A5: 13-fold) and the concentration of carnitine in the liver were increased from 3 wk prepartum to 1 wk postpartum (P < 0.05). From 1 wk to 5 and 14 wk postpartum, mRNA abundances of these genes and hepatic carnitine concentrations were declining (P < 0.05). There were moreover positive correlations between plasma concentrations of non-esterified fatty acids (NEFA) and hepatic carnitine concentrations at 1 wk, 5 wk and 14 wk postpartum (P < 0.05).

Conclusions

The results of this study show for the first time that the expression of hepatic genes of carnitine synthesis and cellular uptake of carnitine is enhanced in dairy cows during early lactation. These changes might provide an explanation for increased hepatic carnitine concentrations observed in 1 wk postpartum and might be regarded as a physiologic means to provide liver cells with sufficient carnitine required for transport of excessive amounts of NEFA during a negative energy balance.
Value-added uses for crude glycerol--a byproduct of biodiesel production
Authors: Yang Fangxia , Hanna Milford A , Sun Runcang
Published: March 2012

Biodiesel is a promising alternative, and renewable, fuel. As its production increases, so does production of the principle co-product, crude glycerol. The effective utilization of crude glycerol will contribute to the viability of biodiesel. In this review, composition and quality factors of crude glycerol are discussed. The value-added utilization opportunities of crude glycerol are reviewed. The majority of crude glycerol is used as feedstock for production of other value-added chemicals, followed by animal feeds.
Centromeric association of small supernumerary marker chromosomes with their sister-chromosomes detected by three dimensional molecular cytogenetics
Authors: Klein Elisabeth , Manvelyan Marina , Simonyan Isabella , Hamid Ahmed B , Guilherme Roberta Santos , Liehr Thomas , Karamysheva Tatyana
Published: March 2012

Background

Small supernumerary marker chromosomes (sSMC) are detected in 0.043% of general population and can be characterized for their chromosomal origin, genetic content and shape by molecular cytogenetic approaches. Even though recently progress was achieved towards genotype-phenotype-correlations of sSMC, nothing is known on the influence that an additional derivative extra chromosome has on the nuclear architecture.

Results

Here we present the first three-dimensional interphase fluorescence in situ hybridization (FISH) studies for the nuclear architecture of sSMC. It could be shown that sSMC derived from chromosomes 15, 16 or 18 preferentially colocalized with one of their corresponding sister chromosomes. This was true in B- and T-lymphocytes as well as in skin fibroblasts. Additionally, a case with a complex sSMC with a karyotype 47,XY,+der(18)t(8;18)(8p23.2 ~ 23.1;18q11.1) was studied. Here the sSMC co-localized with one homologous chromosome 8 instead of 18.

Conclusion

Overall, there is a kind of "attraction" between an sSMC and one of its homologous sister chromosomes. This seems to be transmitted by the euchromatic part of the sSMC rather than its heterochromatic one.
Prevalence and factors associated with cryptococcal antigenemia among severely immunosuppressed HIV‐infected adults in Uganda: a cross‐sectional study
Authors: Oyella Jacinta , Meya David , Bajunirwe Francis , Kamya Moses R
Published: March 2012

Background

Cryptococcal infection is a common opportunistic infection among severely immunosuppressed HIV patients and is associated with high mortality. Positive cryptococcal antigenemia is an independent predictor of cryptococcal meningitis and death in patients with severe immunosuppression. We evaluated the prevalence and factors associated with cryptococcal antigenemia among patients with CD4 counts of 100 cells/mm3 or less in Mulago Hospital, Kampala, Uganda. Screening of a targeted group of HIV patients may enable early detection of cryptococcal infection and intervention before initiating antiretroviral therapy. Factors associated with cryptococcal antigenemia may be used subsequently in resource‐limited settings in screening for cryptococcal infection, and this data may also inform policy for HIV care.

Methods

In this cross‐sectional study, HIV‐infected patients aged 18 years and older with CD4 counts of up to 100 cells/mm3 were enrolled between December 2009 and March 2010. Data on socio‐demographics, physical examinations and laboratory tests were collected. Factors associated with cryptococcal antigenemia were analyzed using multiple logistic regression.

Results

We enrolled 367 participants and the median CD4 count was 23 (IQR 9‐51) cells/mm3. Sixty‐nine (19%) of the 367 participants had cryptococcal antigenemia. Twenty‐four patients (6.5%) had cryptococcal meningitis on cerebrospinal fluid analysis and three had isolated cryptococcal antigenemia. Factors associated with cryptococcal antigenemia included: low body mass index of 15.4 kg/m2 or less (adjusted odds ratio, AOR = 0.5; 95% CI 0.3‐1.0), a CD4+ T cell count of less than 50 cells/mm3 (AOR = 2.7; 95% CI1.2‐6.1), neck pain (AOR = 2.3; 95% CI 1.2‐4.6), recent diagnosis of HIV infection (AOR = 1.9; 95% CI 1.1‐3.6), and meningeal signs (AOR = 7.9; 95% CI 2.9‐22.1). However, at sub‐analysis of asymptomatic patients, absence of neck pain (AOR = 0.5), photophobia (AOR = 0.5) and meningeal signs (AOR = 0.1) were protective against cryptococcal infection.

Conclusions

Cryptococcal antigenemia is common among severely immunosuppressed HIV patients in Mulago Hospital, Kampala, Uganda. Independent predictors of positive serum cryptococcal antigenemia were CD4+ T cell counts of less than 50 cells/mm, low body mass index, neck pain, signs of meningeal irritation, and a recent diagnosis of HIV infection. Routine screening of this category of patients may detect cryptococcosis, and hence provide an opportunity for early intervention. Absence of neck pain, photophobia and meningeal signs were protective against cryptococcal infection compared with symptomatic patients.
Value of self-performed joint counts in rheumatoid arthritis patients near remission
Authors: Radner Helga , Grisar Johannes , Smolen Josef S , Stamm Tanja , Aletaha Daniel
Published: March 2012

Introduction

To determine the validity and reliability of patients' self-performed joint counts compared to joint counts by professional assessors in rheumatoid arthritis (RA) patients in different disease activity states.

Methods

In patients with established RA we determined the inter-rater reliability of joint counts performed by an independent evaluator and the patient using intraclass correlation (ICC), and agreement on activity in individual joints by kappa statistics. We also performed longitudinal analyses to assess consistency of assessments over time. Finally, we investigated the concordance of joint counts of different assessors in patients with different levels of disease activity.

Results

The reliability of patient self-performed joint counts was high when compared to independent objective assessment (ICC; 95%confidence interval (CI)) for the assessment of swelling (0.32; 0.15 to 0.46) and tenderness (0.75; 0.66 to 0.81), with higher agreement for larger joints (kappa: 0.57 and 0.45, respectively) compared to smaller joints (metacarpo-phalangeal joint (MCPs): 0.31 and 0.45; and proximal interphalangeal joint (PIPs): 0.22 and 0.47, for swelling and tenderness, respectively).

Patients in remission according to the Simplified Disease Activity Index (SDAI ≤ 3.3) showed better concordance of the joint counts (swollen joint count (SJC) ties 25/37, tender joint count (TJC) ties 26/37) compared to moderate/high disease activity states (SDAI > 11; MDA/HDA: SJC ties 9/72, TJC ties 21/72). Positive and negative predictive values regarding the presence of SDAI remission were reasonably good (0.86 and 0.95, respectively). A separate training session for patients did not improve the reliability of joint assessment. The results were consistent in the longitudinal analyses.

Conclusions

Self-performed joint counts are particularly useful for monitoring in patients having attained remission, as these patients seem able to detect state of remission.
TNFα modulates protein degradation pathways in rheumatoid arthritis synovial fibroblasts
Authors: Connor Alison M , Mahomed Nizar , Gandhi Rajiv , Keystone Edward C , Berger Stuart A
Published: March 2012

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory and destructive disease of the joint. The synovial lining consists of two main types of cells: synovial fibroblasts and macrophages. The macrophage-derived cytokine TNFα stimulates RA synovial fibroblasts to proliferate and produce growth factors, chemokines, proteinases and adhesion molecules, making them key players in the RA disease process. If proteins are not correctly folded, cellular stress occurs that can be relieved in part by increased degradation of the aberrant proteins by the proteasome or autophagy. We hypothesized that the activity of the protein degradation pathways would be increased in response to TNFα stimulation in RA synovial fibroblasts compared with control fibroblasts.

Methods

Endoplasmic reticulum (ER) stress markers were examined in synovial fibroblasts by immunoblotting and PCR. Use of the autophagy and proteasome protein degradation pathways in response to TNFα stimulation was determined using a combination of experiments involving chemical inhibition of the autophagy or proteasome pathways followed by immunoblotting for the autophagy marker LC3, measurement of proteasome activity and long-lived protein degradation, and determination of cellular viability.

Results

RA synovial fibroblasts are under acute ER stress, and the stress is increased in the presence of TNFα. Autophagy is the main pathway used to relieve the ER stress in unstimulated fibroblasts, and both autophagy and the proteasome are more active in RA synovial fibroblasts compared with control fibroblasts. In response to TNFα, the autophagy pathway but not the proteasome is consistently stimulated, yet there is an increased dependence on the proteasome for cell viability. If autophagy is blocked in the presence of TNFα, an increase in proteasome activity occurs in RA synovial fibroblasts but not in control cells.

Conclusions

TNFα stimulation of synovial fibroblasts results in increased expression of ER stress markers. Survival of synovial fibroblasts is dependent on continuous removal of proteins by both the lysosome/autophagy and ubiquitin/proteasome protein degradation pathways. Both pathways are more active in RA synovial fibroblasts compared with control fibroblasts. These results may provide a better understanding of the mechanism of TNFα on prolonging the survival of synovial fibroblasts in RA tissue.
Clinical features of symptomatic patellofemoral joint osteoarthritis
Authors: Peat George , Duncan Rachel C , Wood Laurence RJ , Thomas Elaine , Muller Sara
Published: March 2012

Introduction

Patellofemoral joint osteoarthritis (OA) is common and leads to pain and disability. However, current classification criteria do not distinguish between patellofemoral and tibiofemoral joint OA. The objective of this study was to provide empirical evidence of the clinical features of patellofemoral joint OA (PFJOA) and to explore the potential for making a confident clinical diagnosis in the community setting.

Methods

This was a population-based cross-sectional study of 745 adults aged ≥50 years with knee pain. Information on risk factors and clinical signs and symptoms was gathered by a self-complete questionnaire, and standardised clinical interview and examination. Three radiographic views of the knee were obtained (weight-bearing semi-flexed posteroanterior, supine skyline and lateral) and individuals were classified into four subsets (no radiographic OA, isolated PFJOA, isolated tibiofemoral joint OA, combined patellofemoral/tibiofemoral joint OA) according to two different cut-offs: 'any OA' and 'moderate to severe OA'. A series of binary logistic and multinomial regression functions were performed to compare the clinical features of each subset and their ability in combination to discriminate PFJOA from other subsets.

Results

Distinctive clinical features of moderate to severe isolated PFJOA included a history of dramatic swelling, valgus deformity, markedly reduced quadriceps strength, and pain on patellofemoral joint compression. Mild isolated PFJOA was barely distinguished from no radiographic OA (AUC 0.71, 95% CI 0.66, 0.76) with only difficulty descending stairs and coarse crepitus marginally informative over age, sex and body mass index. Other cardinal signs of knee OA - the presence of effusion, bony enlargement, reduced flexion range of movement, mediolateral instability and varus deformity - were indicators of tibiofemoral joint OA.

Conclusions

Early isolated PFJOA is clinically manifest in symptoms and self-reported functional limitation but has fewer clear clinical signs. More advanced disease is indicated by a small number of simple-to-assess signs and the relative absence of classic signs of knee OA, which are predominantly manifestations of tibiofemoral joint OA. Confident diagnosis of even more advanced PFJOA may be limited in the community setting.
Functional role of IL-22 in psoriatic arthritis
Authors: Mitra Anupam , Raychaudhuri Smriti K , Raychaudhuri Siba P
Published: March 2012

Introduction

Interleukin-22 (IL-22) is a cytokine of IL-10 family with significant proliferative effect on different cell lines. Immunopathological role of IL-22 has been studied in rheumatoid arthritis (RA) and psoriasis. Here we are reporting the functional role of IL-22 in the inflammatory and proliferative cascades of psoriatic arthritis (PsA).

Method

From peripheral blood and synovial fluid (SF) of PsA (n = 15), RA (n = 15) and osteoarthritis (OA, n = 15) patients, mononuclear cells were obtained and magnetically sorted for CD3+ T cells. Fibroblast like synoviocytes (FLS) were isolated from the synovial tissue of PsA (n = 5), RA (n = 5) and OA (n = 5) patients. IL-22 levels in SF and serum were measured by enzyme linked immunosorbent assay (ELISA). Proliferative effect of human recombinant IL-22 (rIL-22) on FLS was assessed by MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a yellow tetrazole) and CFSE dilution (Carboxyfluorescein succinimidyl ester) assays. Expression of IL-22Rα1 in FLS was determined by western blot.

Results

IL-22 levels were significantly elevated in SF of PsA patients (17.75 ± 3.46 pg/ml) compared to SF of OA (5.03 ± 0.39 pg/ml), p < 0.001. In MTT and CFSE dilution assays, rIL-22 (MTT, OD: 1.27 ± 0.06) induced significant proliferation of FLS derived from PsA patients compared to media (OD: 0.53 ± 0.02), p < 0.001. In addition, rIL-22 induced significantly more proliferation of FLS in presence of TNF-α. IL-22Rα1 was expressed in FLS of PsA, RA and OA patients. Anti IL-22R antibody significantly inhibited the proliferative effect of rIL-22. Further we demonstrated that activated synovial T cells of PsA and RA patients produced significantly more IL-22 than those of OA patients.

Conclusion

SF of PsA patients have higher concentration of IL-22 and rIL-22 induced marked proliferation of PsA derived FLS. Moreover combination of rIL-22 and TNF-α showed significantly more proliferative effect on FLS. IL-22Rα1 was expressed in FLS. Successful inhibition of IL-22 induced FLS proliferation by anti IL-22R antibody suggests that blocking of IL-22/IL-22R interaction may be considered as a novel therapeutic target for PsA.
Making Sense of the Global Health Crisis: Policy Narratives, Conflict, and Global Health Governance
Authors: Ney Steven
Published: March 2012

Health has become a policy issue of global concern. Worried that the unstructured, polycentric, and pluralist nature of global health governance is undermining the ability to serve emergent global public health interests, some commentators are calling for a more systematic institutional response to the “global health crisis.” Yet global health is a complex and uncertain policy issue. This article uses narrative analysis to explore how actors deal with these complexities and how uncertainties affect global health governance. By comparing three narratives in terms of their basic assumptions, the way they define problems as well as the solutions they propose, the analysis shows how the unstructured pluralism of global health policy making creates a wide scope of policy conflict over the global health crisis. This wide scope of conflict enables effective policy-oriented learning about global health issues. The article also shows how exclusionary patterns of cooperation and competition are emerging in health policy making at the global level. These patterns threaten effective learning by risking both polarization of the policy debate and unanticipated consequences of health policy. Avoiding these pitfalls, the analysis suggests, means creating global health governance regimes that promote openness and responsiveness in deliberation about the global health crisis.
Effect of Medication Reconciliation at Hospital Admission on Medication Discrepancies During Hospitalization and at Discharge for Geriatric Patients
Authors: Cornu Pieter , Steurbaut Stephane , Leysen Tinne , Baere Eva De , Ligneel Claudine , Mets Tony , Dupont Alain G
Published: March 2012

Background:

Medication discrepancies have the potential to cause harm. Medication reconciliation by clinical pharmacists aims to prevent discrepancies and other drug-related problems.

Objective:

To determine how often discrepancies in the physician-acquired medication history result in discrepancies during hospitalization and at discharge. Secondary objectives were to determine the influence of clinical pharmacists’ interventions on discrepancies and to investigate possible patient-related determinants for experiencing discrepancies.

Methods:

This was a retrospective, single-center, cohort study of patients who were admitted to the acute geriatric department of a Belgian university hospital and followed up by clinical pharmacists between September 2009 and April 2010. Patients were limited to those 65 years or older who were taking 1 or more prescription drug. Medication reconciliation at admission, during hospitalization, and at discharge was conducted by an independent pharmacist who gathered information via chart reviews.

Results:

The reconciliation process at admission identified 681 discrepancies in 199 patients. Approximately 81.9% (163) of patients had at least 1 discrepancy in the physician-acquired medication history. The clinical pharmacists performed 386 interventions, which were accepted in 279 cases (72.3%). A quarter of the medication history discrepancies (165; 24.2%) resulted in discrepancies during hospitalization, mostly because the intervention was not accepted. At discharge, 278 medication history discrepancies (40.8%) resulted in discrepancies in the discharge letter, accounting for 50.2% of all 554 discrepancies identified in the discharge letters. The likelihood for experiencing discrepancies at admission increased by 47% for every additional drug listed in the medication history.

Conclusions:

Discrepancies in the physician-acquired medication history at admission do not always correlate with discrepancies during hospitalization because of clinical pharmacists’ interventions; however, discrepancies at admission may be associated with at least half of the discrepancies at discharge. Clinical pharmacist–conducted medication reconciliation can reduce these discrepancies, provided the erroneous information in the physician-acquired medication history is corrected and each intentional change in the medication plan is well documented during hospitalization and at discharge.
Prolonged Disynaptic Inhibition in the Cortex Mediated by Slow, Non-α7 Nicotinic Excitation of a Specific Subset of Cortical Interneurons
Authors: Arroyo Sergio , Bennett Corbett , Aziz David , Brown Solange P. , Hestrin Shaul
Published: March 2012

Cholinergic activation of nicotinic receptors in the cortex plays a critical role in arousal, attention, and learning. Here we demonstrate that cholinergic axons from the basal forebrain of mice excite a specific subset of cortical interneurons via a remarkably slow, non-α7 nicotinic receptor-mediated conductance. In turn, these inhibitory cells generate a delayed and prolonged wave of disynaptic inhibition in neighboring cortical neurons, altering the spatiotemporal pattern of inhibition in cortical circuits.
Spike Resonance Properties in Hippocampal O-LM Cells Are Dependent on Refractory Dynamics
Authors: Kispersky Tilman J. , Fernandez Fernando R. , Economo Michael N. , White John A.
Published: March 2012

During a wide variety of behaviors, hippocampal field potentials show significant power in the theta (4–12 Hz) frequency range and individual neurons commonly phase-lock with the 4–12 Hz field potential. The underlying cellular and network mechanisms that generate the theta rhythm, however, are poorly understood. Oriens-lacunosum moleculare (O-LM) interneurons have been implicated as crucial contributors to generating theta in local hippocampal circuits because of their unique axonal projections, slow synaptic kinetics and the fact that spikes are phase-locked to theta field potentialsin vivo. We performed experiments in brain slice preparations from Long–Evans rats to investigate the ability of O-LM cells to generate phase-locked spike output in response to artificial synaptic inputs. We find that O-LM cells do not respond with any preference in spike output at theta frequencies when injected with broadband artificial synaptic inputs. However, when presented with frequency-modulated inputs, O-LM spike output shows the ability to phase-lock well to theta-modulated inputs, despite their strong low-pass profiles of subthreshold membrane impedance. This result was dependent on spike refractory dynamics and could be controlled by real-time manipulation of the postspike afterhyperpolarization. Finally, we show that the ability of O-LM cells to phase-lock well to theta-rich inputs is independent of the h-current, a membrane mechanism often implicated in the generation of theta frequency activity.
Repetitive Intermittent Hypoxia Induces Respiratory and Somatic Motor Recovery after Chronic Cervical Spinal Injury
Authors: Lovett-Barr Mary R. , Satriotomo Irawan , Muir Gillian D. , Wilkerson Julia E. R. , Hoffman Michael S. , Vinit Stéphane , Mitchell Gordon S.
Published: March 2012

Spinal injury disrupts connections between the brain and spinal cord, causing life-long paralysis. Most spinal injuries are incomplete, leaving spared neural pathways to motor neurons that initiate and coordinate movement. One therapeutic strategy to induce functional motor recovery is to harness plasticity in these spared neural pathways. Chronic intermittent hypoxia (CIH) (72 episodes per night, 7 nights) increases synaptic strength in crossed spinal synaptic pathways to phrenic motoneurons below a C2 spinal hemisection. However, CIH also causes morbidity (e.g., high blood pressure, hippocampal apoptosis), rendering it unsuitable as a therapeutic approach to chronic spinal injury. Less severe protocols of repetitive acute intermittent hypoxia may elicit plasticity without associated morbidity. Here we demonstrate that daily acute intermittent hypoxia (dAIH; 10 episodes per day, 7 d) induces motor plasticity in respiratory and nonrespiratory motor behaviors without evidence for associated morbidity. dAIH induces plasticity in spared, spinal pathways to respiratory and nonrespiratory motor neurons, improving respiratory and nonrespiratory (forelimb) motor function in rats with chronic cervical injuries. Functional improvements were persistent and were mirrored by neurochemical changes in proteins that contribute to respiratory motor plasticity after intermittent hypoxia (BDNF and TrkB) within both respiratory and nonrespiratory motor nuclei. Collectively, these studies demonstrate that repetitive acute intermittent hypoxia may be an effective and non-invasive means of improving function in multiple motor systems after chronic spinal injury.
Corticomuscular Coherence Is Tuned to the Spontaneous Rhythmicity of Speech at 2–3 Hz
Authors: Ruspantini Irene , Saarinen Timo , Belardinelli Paolo , Jalava Antti , Parviainen Tiina , Kujala Jan , Salmelin Riitta
Published: March 2012

Human speech features rhythmicity that frames distinctive, fine-grained speech patterns. Speech can thus be counted among rhythmic motor behaviors that generally manifest characteristic spontaneous rates. However, the critical neural evidence for tuning of articulatory control to a spontaneous rate of speech has not been uncovered. The present study examined the spontaneous rhythmicity in speech production and its relationship to cortex–muscle neurocommunication, which is essential for speech control. Our MEG results show that, during articulation, coherent oscillatory coupling between the mouth sensorimotor cortex and the mouth muscles is strongest at the frequency of spontaneous rhythmicity of speech at 2–3 Hz, which is also the typical rate of word production. Corticomuscular coherence, a measure of efficient cortex–muscle neurocommunication, thus reveals behaviorally relevant oscillatory tuning for spoken language.
Synaptotagmin 1 Is Necessary for the Ca2+Dependence of Clathrin-Mediated Endocytosis
Authors: Yao Li-Hua , Rao Yan , Varga Kelly , Wang Chun-Yang , Xiao Peng , Lindau Manfred , Gong Liang-Wei
Published: March 2012

The role of Ca2+in synaptic vesicle endocytosis remains uncertain due to the diversity in various preparations where several forms of endocytosis may contribute variably in different conditions. Although recent studies have demonstrated that Ca2+is important for clathrin-mediated endocytosis (CME), the mechanistic role of Ca2+in CME remains to be elucidated. By monitoring CME of single vesicles in mouse chromaffin cells with cell-attached capacitance measurements that offer millisecond time resolution, we demonstrate that the dynamics of vesicle fission during CME is Ca2+dependent but becomes Ca2+independent in synaptotagmin 1 (Syt1) knock-out cells. Our results thus suggest that Syt1 is necessary for the Ca2+dependence of CME.
Categorical Speech Processing in Broca's Area: An fMRI Study Using Multivariate Pattern-Based Analysis
Authors: Lee Yune-Sang , Turkeltaub Peter , Granger Richard , Raizada Rajeev D. S.
Published: March 2012

Although much effort has been directed toward understanding the neural basis of speech processing, the neural processes involved in the categorical perception of speech have been relatively less studied, and many questions remain open. In this functional magnetic resonance imaging (fMRI) study, we probed the cortical regions mediating categorical speech perception using an advanced brain-mapping technique, whole-brain multivariate pattern-based analysis (MVPA). Normal healthy human subjects (native English speakers) were scanned while they listened to 10 consonant–vowel syllables along the /ba/–/da/ continuum. Outside of the scanner, individuals' own category boundaries were measured to divide the fMRI data into /ba/ and /da/ conditions per subject. The whole-brain MVPA revealed that Broca's area and the left pre-supplementary motor area evoked distinct neural activity patterns between the two perceptual categories (/ba/ vs /da/). Broca's area was also found when the same analysis was applied to another dataset (Raizada and Poldrack, 2007), which previously yielded the supramarginal gyrus using a univariate adaptation–fMRI paradigm. The consistent MVPA findings from two independent datasets strongly indicate that Broca's area participates in categorical speech perception, with a possible role of translating speech signals into articulatory codes. The difference in results between univariate and multivariate pattern-based analyses of the same data suggest that processes in different cortical areas along the dorsal speech perception stream are distributed on different spatial scales.
Lateral Hypothalamic Orexin/Hypocretin Neurons That Project to Ventral Tegmental Area Are Differentially Activated with Morphine Preference
Authors: Richardson Kimberlei A. , Aston-Jones Gary
Published: March 2012

Orexin (or hypocretin) is synthesized exclusively in dorsomedial, perifornical, and lateral hypothalamus (LH). These neurons are implicated in several functions, including reward processing. We examined the ventral tegmental area (VTA) as a possible site of orexin action for drug preference during protracted morphine abstinence, and studied functional topography of orexin projections to VTA. Male Sprague Dawley rats were used to investigate whether orexin cells that project to VTA exhibit Fos activation with morphine conditioned place preference (CPP), and whether these cells exhibit increased Fos with morphine CPP during protracted abstinence. Unilateral injections of a retrograde tracer (WGA-Au, 350–400 nl) were made into the VTA or a nonreward area, locus ceruleus, and morphine or placebo pellets were implanted for 14 d. Approximately 2 weeks after pellet removal (post dependence), CPP conditioning and testing were conducted. Triple labeling for WGA-Au, Fos, and orexin revealed that the percentage of VTA-projecting orexin neurons Fos activated on the CPP test day significantly increased in post-dependent (vs nondependent) rats, and was exclusive to LH orexin neurons (not dorsomedial or perifornical). Post-dependent animals showed a positive correlation between CPP scores and percentages of Fos-activated, caudal VTA-projecting LH orexin cells. Unlike afferents to caudal VTA, percentages of rostral VTA-projecting, LH orexin cells that were Fos activated showed a positive correlation with CPP only in nondependent animals. Fos in LC-projecting orexin cells was not correlated with CPP in any group. These results indicate that VTA is a heterogeneous and functionally significant target of orexin neurons for morphine reward during protracted abstinence.
ArfGAP1 Is a GTPase Activating Protein for LRRK2: Reciprocal Regulation of ArfGAP1 by LRRK2
Authors: Xiong Yulan , Yuan Changqing , Chen Rong , Dawson Ted M. , Dawson Valina L.
Published: March 2012

Both sporadic and autosomal dominant forms of Parkinson's disease (PD) have been causally linked to mutations in leucine-rich repeat kinase 2 (LRRK2), a large protein with multiple domains. The kinase domain plays an important role in LRRK2-mediated toxicity. Although a number of investigations have focused on LRRK2 kinase activity, less is known about the GTPase function of LRRK2. The activity of GTPases is regulated by GTPase activating proteins (GAPs) and GTP exchange factors. Here, we identify ArfGAP1 as the first GAP for LRRK2. ArfGAP1 binds LRRK2 predominantly via the WD40 and kinase domain of LRRK2, and it increases LRRK2 GTPase activity and regulates LRRK2 toxicity bothin vitroandin vivoinDrosophila melanogaster. Unexpectedly, ArfGAP1 is an LRRK2 kinase substrate whose GAP activity is inhibited by LRRK2, whereas wild-type and G2019S LRRK2 autophosphorylation and kinase activity are significantly reduced in the presence of ArfGAP1. Overexpressed ArfGAP1 exhibits toxicity that is reduced by LRRK2 bothin vitroandin vivo. Δ64–ArfGAP1, a dominant-negative ArfGAP1, and shRNA knockdown of ArfGAP1 reduce LRRK2 toxicity. Thus, LRRK2 and ArfGAP1 reciprocally regulate the activity of each other. Our results provide insight into the basic pathobiology of LRRK2 and indicate an important role for the GTPase domain and ArfGAP1 in LRRK2-mediated toxicity. These data suggest that agents targeted toward regulation of LRRK2 GTP hydrolysis might be therapeutic agents for the treatment of PD.
The Microtubule-Stabilizing Agent, Epothilone D, Reduces Axonal Dysfunction, Neurotoxicity, Cognitive Deficits, and Alzheimer-Like Pathology in an Interventional Study with Aged Tau Transgenic Mice
Authors: Zhang Bin , Carroll Jenna , Trojanowski John Q. , Yao Yuemang , Iba Michiyo , Potuzak Justin S. , Hogan Anne-Marie L. , Xie Sharon X. , Ballatore Carlo , Smith Amos B. , Lee Virginia M.-Y. , Brunden Kurt R.
Published: March 2012

Neurodegenerative tauopathies, such as Alzheimer's disease (AD), are characterized by insoluble deposits of hyperphosphorylated tau protein within brain neurons. Increased phosphorylation and decreased solubility has been proposed to diminish normal tau stabilization of microtubules (MTs), thereby leading to neuronal dysfunction. Earlier studies have provided evidence that small molecule MT-stabilizing drugs that are used in the treatment of cancer may have utility in the treatment of tauopathies. However, it has not been established whether treatment with a small molecule MT-stabilizing compound will provide benefit in a transgenic model with pre-existing tau pathology, as would be seen in human patients with clinical symptoms. Accordingly, we describe here an interventional study of the brain-penetrant MT-stabilizing agent, epothilone D (EpoD), in aged PS19 mice with existing tau pathology and related behavioral deficits. EpoD treatment reduced axonal dystrophy and increased axonal MT density in the aged PS19 mice, which led to improved fast axonal transport and cognitive performance. Moreover, the EpoD-treated PS19 mice had less forebrain tau pathology and increased hippocampal neuronal integrity, with no dose-limiting side effects. These data reveal that brain-penetrant MT-stabilizing drugs hold promise for the treatment of AD and related tauopathies, and that EpoD could be a candidate for clinical testing.
Neural Activity in Cortical Area V4 Underlies Fine Disparity Discrimination
Authors: Shiozaki Hiroshi M. , Tanabe Seiji , Doi Takahiro , Fujita Ichiro
Published: March 2012

Primates are capable of discriminating depth with remarkable precision using binocular disparity. Neurons in area V4 are selective for relative disparity, which is the crucial visual cue for discrimination of fine disparity. Here, we investigated the contribution of V4 neurons to fine disparity discrimination. Monkeys discriminated whether the center disk of a dynamic random-dot stereogram was in front of or behind its surrounding annulus. We first behaviorally tested the reference frame of the disparity representation used for performing this task. After learning the task with a set of surround disparities, the monkey generalized its responses to untrained surround disparities, indicating that the perceptual decisions were generated from a disparity representation in a relative frame of reference. We then recorded single-unit responses from V4 while the monkeys performed the task. On average, neuronal thresholds were higher than the behavioral thresholds. The most sensitive neurons reached thresholds as low as the psychophysical thresholds. For subthreshold disparities, the monkeys made frequent errors. The variable decisions were predictable from the fluctuation in the neuronal responses. The predictions were based on a decision model in which each V4 neuron transmits the evidence for the disparity it prefers. We finally altered the disparity representation artificially by means of microstimulation to V4. The decisions were systematically biased when microstimulation boosted the V4 responses. The bias was toward the direction predicted from the decision model. We suggest that disparity signals carried by V4 neurons underlie precise discrimination of fine stereoscopic depth.
In VivoNerve–Macrophage Interactions Following Peripheral Nerve Injury
Authors: Rosenberg Allison F. , Wolman Marc A. , Franzini-Armstrong Clara , Granato Michael
Published: March 2012

In vertebrates, the peripheral nervous system has retained its regenerative capacity, enabling severed axons to reconnect with their original synaptic targets. While it is well documented that a favorable environment is critical for nerve regeneration, the complex cellular interactions between injured nerves with cells in their environment, as well as the functional significance of these interactions, have not been determinedin vivoand in real time. Here we provide the first minute-by-minute account of cellular interactions between laser transected motor nerves and macrophages in live intact zebrafish. We show that macrophages arrive at the lesion site long before axon fragmentation, much earlier than previously thought. Moreover, we find that axon fragmentation triggers macrophage invasion into the nerve to engulf axonal debris, and that delaying nerve fragmentation in a Wldsmodel does not alter macrophage recruitment but induces a previously unknown ‘nerve scanning’ behavior, suggesting that macrophage recruitment and subsequent nerve invasion are controlled by separate mechanisms. Finally, we demonstrate that macrophage recruitment, thought to be dependent on Schwann cell-derived signals, occurs independently of Schwann cells. Thus, live cell imaging defines novel cellular and functional interactions between injured nerves and immune cells.