bluuebunny/crossref_metadata_2025 huggingface dataset:
Patients' Perspectives of a Multifaceted Intervention With a Focus on Technology
Authors: Lambert-Kerzner Anne , Havranek Edward P. , Plomondon Mary E. , Albright Karen , Moore Ashley , Gryniewicz Kelsey , Magid David , Ho P. Michael
Published: October 2010

Background—

Few studies have investigated the effectiveness of multifaceted interventions from the study participants' perspective. We conducted qualitative interviews to understand patients' experiences with a multifaceted blood pressure (BP) control intervention involving interactive voice response technology, home BP monitoring, and pharmacist-led BP management. In the randomized study, the intervention resulted in clinically significant decreases in BP.

Methods and Results—

We used insights generated from in-depth interviews from all study participants randomly assigned to the multifaceted intervention or usual care (n=146) to create a model explaining the observed improvements in health behavior and clinical outcomes. The data were analyzed using qualitative content analysis methods and consultative and reflexive team analysis. Six explanatory factors emerged from the patients' interviews: (1) improved relationships with medical personnel; (2) increased knowledge of hypertension; (3) increased participation in their health care and personal empowerment; (4) greater understanding of the impact of health behavior on BP; (5) high satisfaction with technology used in the intervention; and, for some patients, (6) increased health care utilization. Eighty-six percent of the intervention patients and 62% of the usual care patients stated that study participation had a positive effect on them. Of those expressing a positive effect, 68% (intervention) and 55% (usual care) reached their systolic BP goal.

Conclusions—

Establishing bidirectional conversations between patients and providers is a key element of successful hypertension management. Home BP monitoring coupled with interactive voice response technology reporting facilitates such conversations.
Biofilms Inducing Ultra-low Friction on Titanium
Authors: Souza J.C.M. , Henriques M. , Oliveira R. , Teughels W. , Celis J.-P. , Rocha L.A.
Published: October 2010

Biofilm formation is widely reported in the literature as a problem in the healthcare, environmental, and industrial sectors. However, the role of biofilms in sliding contacts remains unclear. Friction during sliding was analyzed for titanium covered with mixed biofilms consisting of Streptococcus mutans and Candida albicans. The morphology of biofilms on titanium surfaces was evaluated before, during, and after sliding tests. Very low friction was recorded on titanium immersed in artificial saliva and sliding against alumina in the presence of biofilms. The complex structure of biofilms, which consist of microbial cells and their hydrated exopolymeric matrix, acts like a lubricant. A low friction in sliding contacts may have major significance in the medical field. The composition and structure of biofilms are shown to be key factors for an understanding of friction behavior of dental implant connections and prosthetic joints. For instance, a loss of mechanical integrity of dental implant internal connections may occur as a consequence of the decrease in friction caused by biofilm formation. Consequently, the study of the exopolymeric matrix can be important for the development of high-performance novel joint-based systems for medical and other engineering applications.
Oral Health Literacy among Female Caregivers
Authors: Vann W.F. , Lee J.Y. , Baker D. , Divaris K.
Published: October 2010

The aim of this study was to investigate the association of female caregivers’ oral health literacy with their knowledge, behaviors, and the reported oral health status of their young children. Data on caregivers’ literacy, knowledge, behaviors, and children’s oral health status were used from structured interviews with 1158 caregiver/child dyads from a low-income population. Literacy was measured with REALD-30. Caregivers’ and children’s median ages were 25 yrs (range = 17-65) and 15 mos (range = 1-59), respectively. The mean literacy score was 15.8 (SD = 5.3; range = 1-30). Adjusted for age, education, and number of children, low literacy scores (< 13 REALD-30) were associated with decreased knowledge (OR = 1.86; 95% CI = 1.41, 2.45) and poorer reported oral health status (OR = 1.44; 95% CI = 1.02, 2.05). Lower caregiver literacy was associated with deleterious oral health behaviors, including nighttime bottle use and no daily brushing/cleaning. Caregiver oral health literacy has a multidimensional impact on reported oral health outcomes in infants and young children.
Indoor Air Pollution from Biomass Burning Activates Akt in Airway Cells and Peripheral Blood Lymphocytes
Authors: Mondal Nandan K. , Roy Amrita , Mukherjee Bidisha , Das Debangshu , Ray Manas R.
Published: October 2010

Biomass burning is a major source of indoor air pollution in rural India. The authors investigated in this study whether cumulative exposures to biomass smoke cause activation of the serine/threonine kinase Akt in airway cells and peripheral blood lymphocytes (PBL). For this, the authors enrolled 87 premenopausal (median age 34 years), nonsmoking women who used to cook with biomass (wood, dung, crop wastes) and 85 age-matched control women who cooked with cleaner fuel liquefied petroleum gas. Immunocytochemical and immunoblotting assays revealed significantly higher levels of phosphorylated forms of Akt protein (p-Aktser473 and p-Aktthr308) in PBL, airway epithelial cells, alveolar macrophages, and neutrophils in sputum of biomass-using women than control. Akt activation in biomass users was associated with marked rise in generation of reactive oxygen species and concomitant depletion of superoxide dismutase. Measurement of particulate matter having a diameter of less than 10 and 2.5 µm in indoor air by real-time aerosol monitor showed 2 to 4 times more particulate pollution in biomass-using households, and Akt activation was positively associated with particulate pollution after controlling potential confounders. The findings suggest that chronic exposure to biomass smoke activates Akt, possibly via generation of oxidative stress.
Military-Madrasa-Mullah Complex
Authors: Mohanty Sanjeeb Kumar , Mahanty Jinendra Nath
Published: October 2010

Since the 1970s, the military-madrasa-mullah complex in Pakistan has nurtured a relationship that has transformed Islam into a fundamentalist creed which has spawned a militant brand of Islam to fight its existential enemies. In the absence of competing ideologies and by confusing religiosity with religion, the Islamist radicals are emotionally tempted towards the ideological appeals of extremism. The political use of religion (Islam) in terms of jihad to fight the Soviets was a primary factor in militarising the Pakistani society. The jihadis, in an effort to take Islam back to its pristine glory, have transformed the rhetoric of jihad into actual violence through promotion of Islamic terror. With least commitment to the existing social order, these Islamists with their politics of extremism have defamed Islam in general and Pakistan in particular.
Using Audacity and One Classroom Computer to Experiment With Timbre
Authors: Smith Kenneth H.
Published: October 2010

One computer, one class, and one educator can be an effective combination to engage students as a group in music composition, performance, and analysis. Having one desktop computer and a television monitor in the music classroom is not an uncommon or new scenario, especially in a time when many school budgets are being cut. This article investigates the creative applications of inexpensive software, such as Audacity, that students can use to analyze and create music individually or as a group. Audacity provides many tools to manipulate the musical elements of pitch, tempo, dynamics, and timbre. Analysis tools allow students to visualize sound waves and to experiment with the relationship of overtones to the sound of unique instrumental and vocal timbres. The manipulation of timbres provides one example of using a simple audio editing computer application to engage students in group instruction and experimentation. Several other strategies for using Audacity with students are included in a table. Teachers are encouraged to think of creative ways to use computer software beyond its primary function.
Aspects of quality of life in adults diagnosed with autism in childhood
Authors: Billstedt Eva , Gillberg I. Carina , Gillberg Christopher
Published: October 2010

The present study is a long-term prospective follow-up study of a population-based cohort of 120 individuals diagnosed with autism in childhood, followed into late adolescence/early adulthood. Specific aims of the study were to attempt to measure and study social aspects/quality of life in those 108 individuals with autism alive and available for study at the time of follow-up (13—22 years after original diagnosis). A newly constructed scale for rating ‘autism-friendly environment’/quality of life was used alongside a structured parent/carer interview assessing current occupation, educational history, services provided, accommodation type, and recreational activities. The majority of the group with autism remained dependent on parents/caregivers for support in education, accommodation and occupational situations. In spite of this, the estimation of the study group’s general quality of life was encouragingly positive. Nevertheless, there was an obvious need for improvements in the areas of occupation and recreational activities. Future studies need to look in more depth at the concept of an autism-friendly environment and develop more detailed quality of life assessment tools relevant for people in the autism spectrum.
Explaining autism
Authors: Hobson R. Peter
Published: October 2010

My aim in this paper is to present reasons for adopting a focus on the development of self/other-awareness when characterizing the developmental psychopathology of autism. The strengths of such a position include an emphasis on children’s emotional relations with embodied persons as foundational for their growing understanding of minds. I give special attention to the process of identifying with the attitudes of others, and experience of other-person-centred emotions, for the development of communication and thinking. The study of limitations in these aspects of self-other relatedness among individuals with autism is pivotal for understanding the pathogenesis of the syndrome.
Delayed video self-recognition in children with high Vo functioning autism and Asperger’s disorder
Authors: Dissanayake Cheryl , Shembrey Joh , Suddendorf Thomas
Published: October 2010

Two studies are reported which investigate delayed video self-recognition (DSR) in children with autistic disorder and Asperger’s disorder relative to one another and to their typically developing peers. A secondary aim was to establish whether DSR ability is dependent on metarepresentational ability. Children’s verbal and affective responses to their image were also measured. Three groups of male children between 5 and 9 years, comprising 15 with high-functioning autistic disorder (HFA), 12 with Asperger’s disorder (AspD), and 15 typically developing (TD) children, participated in Study 1. Study 2 included two groups of younger children (18 HFA; 18 TD) aged 4 to 7 years. Participant groups in each study were equally able to recognize themselves using delayed video feedback, and responded to their marked image with positive affect. This was so even amongst children with HFA who were impaired in their performance on false belief tasks, casting doubt on a metarepresentational basis of DSR.
Social Stories™ to improve social skills in children with autism spectrum disorder
Authors: Karkhaneh Mohammad , Clark Brenda , Ospina Maria B. , Seida Jennifer C. , Smith Veronica , Hartling Lisa
Published: October 2010

Over the past 20 years a variety of treatments have been developed to remediate deficits associated with autism. Since the early 1990s, Social Stories™ have been suggested to positively affect the social development of children with autism spectrum disorder (ASD). Despite much research, there remains uncertainty regarding the effectiveness of this modality. We conducted a systematic review of the literature using pre-defined, rigorous methods. Studies were considered eligible if they were controlled trials evaluating Social Stories™ among persons with ASD. Two reviewers independently screened articles for inclusion, applied eligibility criteria, extracted data, and assessed methodological quality. A qualitative analysis was conducted on six eligible controlled trials. Five of the six trials showed statistically significant benefits for a variety of outcomes related to social interaction. This review underscores the need for further rigorous research and highlights some outstanding questions regarding maintenance and generalization of the benefits of Social Stories™.
Talin1 is required for integrin-dependent B lymphocyte homing to lymph nodes and the bone marrow but not for follicular B-cell maturation in the spleen
Authors: Manevich-Mendelson Eugenia , Grabovsky Valentin , Feigelson Sara W. , Cinamon Guy , Gore Yael , Goverse Gera , Monkley Susan J. , Margalit Raanan , Melamed Doron , Mebius Reina E. , Critchley David R. , Shachar Idit , Alon Ronen
Published: October 2010

Talin1 is a key integrin coactivator. We investigated the roles of this cytoskeletal adaptor and its target integrins in B-cell lymphogenesis, differentiation, migration, and function. Using CD19 Cre-mediated depletion of talin1 selectively in B cells, we found that talin1 was not required for B-cell generation in the bone marrow or for the entry of immature B cells to the white pulp of the spleen. Loss of talin1 also did not affect B-cell maturation into follicular B cells but compromised differentiation of marginal zone B cells. Nevertheless, serum IgM and IgG levels remained normal. Ex vivo analysis of talin1-deficient spleen B cells indicated a necessary role for talin1 in LFA-1 and VLA-4 activation stimulated by canonical agonists, but not in B-cell chemotaxis. Consequently, talin1 null B splenocytes could not enter lymph nodes nor return to the bone marrow. Talin1 deficiency in B cells was also impaired in the humoral response to a T cell-dependent antigen. Collectively, these results indicate that talin1 is not required for follicular B-cell maturation in the spleen or homeostatic humoral immunity but is critical for integrin-dependent B lymphocyte emigration to lymph nodes and optimal immunity against T-dependent antigens.
Evaluation of endogenous references for gene expression profiling in different tissues of the oriental fruit fly Bactrocera dorsalis (Diptera: Tephritidae)
Authors: Shen Guang-Mao , Jiang Hong-Bo , Wang Xiao-Na , Wang Jin-Jun
Published: October 2010

Background

Quantitative real-time reverse transcriptase PCR (RT-qPCR) has been widely used for quantification of mRNA as a way to determine key genes involved in different biological processes. For accurate gene quantification analysis, normalization of RT-qPCR data is absolutely essential. To date, normalization is most frequently achieved by the use of internal controls, often referred to as reference genes. However, several studies have shown that the reference genes used for the quantification of mRNA expression can be affected by the experimental set-up or cell type resulting in variation of the expression level of these key genes. Therefore, the evaluation of reference genes is critical for gene expression profiling, which is often neglected in gene expression studies of insects. For this purpose, ten candidate reference genes were investigated in three different tissues (midgut, Malpighian tubules, and fat body) of the oriental fruit fly, Bactrocera dorsalis (Hendel).

Results

Two different programs, geNorm and Normfinder, were used to analyze the data. According to geNorm, α-TUB + ACT5 are the most appropriate reference genes for gene expression profiling across the three different tissues in the female flies, while ACT3 + α-TUB are considered as the best for males. Furthermore, we evaluated the stability of the candidate reference genes to determine the sexual differences in the same tissue. In the midgut and Malpighian tubules, ACT2 + α-TUB are the best choice for both males and females. However, α-TUB + ACT1 are the best pair for fat body. Meanwhile, the results calculated by Normfinder are quite the same as the results with geNorm; α-TUB is always one of the most stable genes in each sample validated by the two programs.

Conclusions

In this study, we validated the suitable reference genes for gene expression profiling in different tissues of B. dorsalis. Moreover, appropriate reference genes were selected out for gene expression profiling of the same tissues taking the sexual differences into consideration. This work not only formed a solid basis for future gene expression study in B. dorsalis, but also will serve as a resource to screen reference genes for gene expression studies in any other insects.
Genetic and epigenetic characteristics of human multiple hepatocellular carcinoma
Authors: Taniguchi Kazuya , Yamada Terumasa , Sasaki Yo , Kato Kikuya
Published: October 2010

Background

Multiple carcinogenesis is one of the major characteristics of human hepatocellular carcinoma (HCC). The history of multiple tumors, that is, whether they derive from a common precancerous or cancerous ancestor or individually from hepatocytes, is a major clinical issue. Multiple HCC is clinically classified as either intratumor metastasis (IM) or multicentric carcinogenesis (MC). Molecular markers that differentiate IM and MC are of interest to clinical practitioners because the clinical diagnoses of IM and MC often lead to different therapies.

Methods

We analyzed 30 multiple tumors from 15 patients for somatic mutations of cancer-related genes, chromosomal aberrations, and promoter methylation of tumor suppressor genes using techniques such as high-resolution melting, array-comparative genomic hybridization (CGH), and quantitative methylation-specific PCR.

Results

Somatic mutations were found in TP53 and CTNNB1 but not in CDKN2A or KRAS. Tumors from the same patient did not share the same mutations. Array-CGH analysis revealed variations in the number of chromosomal aberrations, and the detection of common aberrations in tumors from the same patient was found to depend on the total number of chromosomal aberrations. A promoter methylation analysis of genes revealed dense methylation in HCC but not in the adjacent non-tumor tissue. The correlation coefficients (r) of methylation patterns between tumors from the same patient were more similar than those between tumors from different patients. In total, 47% of tumor samples from the same patients had an r ≥ 0.8, whereas, in contrast, only 18% of tumor samples from different patients had an r ≥ 0.8 (p = 0.01). All IM cases were highly similar; that is, r ≥ 0.8 (p = 0.025).

Conclusions

The overall scarcity of common somatic mutations and chromosomal aberrations suggests that biological IM is likely to be rare. Tumors from the same patient had a methylation pattern that was more similar than those from different patients. As all clinical IM cases exhibited high similarity, the methylation pattern may be applicable to support the clinical diagnosis of IM and MC.
Impact of maternal metabolic abnormalities in pregnancy on human milk and subsequent infant metabolic development: methodology and design
Authors: Ley Sylvia H , O'Connor Deborah L , Retnakaran Ravi , Hamilton Jill K , Sermer Mathew , Zinman Bernard , Hanley Anthony J
Published: October 2010

Background

Childhood obesity is on the rise and is a major risk factor for type 2 diabetes later in life. Recent evidence indicates that abnormalities that increase risk for diabetes may be initiated early in infancy. Since the offspring of women with diabetes have an increased long-term risk for obesity and type 2 diabetes, the impact of maternal metabolic abnormalities on early nutrition and infant metabolic trajectories is of considerable interest. Human breast milk, the preferred food during infancy, contains not only nutrients but also an array of bioactive substances including metabolic hormones. Nonetheless, only a few studies have reported concentrations of metabolic hormones in human milk specifically from women with metabolic abnormalities. We aim to investigate the impact of maternal metabolic abnormalities in pregnancy on human milk hormones and subsequently on infant development over the first year of life. The objective of this report is to present the methodology and design of this study.

Methods/Design

The current investigation is a prospective study conducted within ongoing cohort studies of women and their offspring. Pregnant women attending outpatient obstetrics clinics in Toronto, Canada were recruited. Between April 2009 and July 2010, a total of 216 pregnant women underwent a baseline oral glucose tolerance test and provided medical and lifestyle history. Follow-up visits and telephone interviews are conducted and expected to be completed in October 2011. Upon delivery, infant birth anthropometry measurements and human breast milk samples are collected. At 3 and 12 months postpartum, mothers and infants are invited for follow-up assessments. Interim telephone interviews are conducted during the first year of offspring life to characterize infant feeding and supplementation behaviors.

Discussion

An improved understanding of the link between maternal metabolic abnormalities in pregnancy and early infant nutrition may assist in the development of optimal prevention and intervention strategies and in the protection of nutritionally vulnerable offspring who are at risk for obesity and diabetes later in life.
Monitoring of malaria parasite resistance to chloroquine and sulphadoxine-pyrimethamine in the Solomon Islands by DNA microarray technology
Authors: Ballif Marie , Hii Jeffrey , Marfurt Jutta , Crameri Andreas , Fafale Adam , Felger Ingrid , Beck Hans-Peter , Genton Blaise
Published: October 2010

Background

Little information is available on resistance to anti-malarial drugs in the Solomon Islands (SI). The analysis of single nucleotide polymorphisms (SNPs) in drug resistance associated parasite genes is a potential alternative to classical time- and resource-consuming in vivo studies to monitor drug resistance. Mutations in pfmdr1 and pfcrt were shown to indicate chloroquine (CQ) resistance, mutations in pfdhfr and pfdhps indicate sulphadoxine-pyrimethamine (SP) resistance, and mutations in pfATPase6 indicate resistance to artemisinin derivatives.

Methods

The relationship between the rate of treatment failure among 25 symptomatic Plasmodium falciparum-infected patients presenting at the clinic and the pattern of resistance-associated SNPs in P. falciparum infecting 76 asymptomatic individuals from the surrounding population was investigated. The study was conducted in the SI in 2004. Patients presenting at a local clinic with microscopically confirmed P. falciparum malaria were recruited and treated with CQ+SP. Rates of treatment failure were estimated during a 28-day follow-up period. In parallel, a DNA microarray technology was used to analyse mutations associated with CQ, SP, and artemisinin derivative resistance among samples from the asymptomatic community. Mutation and haplotype frequencies were determined, as well as the multiplicity of infection.

Results

The in vivo study showed an efficacy of 88% for CQ+SP to treat P. falciparum infections. DNA microarray analyses indicated a low diversity in the parasite population with one major haplotype present in 98.7% of the cases. It was composed of fixed mutations at position 86 in pfmdr1, positions 72, 75, 76, 220, 326 and 356 in pfcrt, and positions 59 and 108 in pfdhfr. No mutation was observed in pfdhps or in pfATPase6. The mean multiplicity of infection was 1.39.

Conclusion

This work provides the first insight into drug resistance markers of P. falciparum in the SI. The obtained results indicated the presence of a very homogenous P. falciparum population circulating in the community. Although CQ+SP could still clear most infections, seven fixed mutations associated with CQ resistance and two fixed mutations related to SP resistance were observed. Whether the absence of mutations in pfATPase6 indicates the efficacy of artemisinin derivatives remains to be proven.
Regulation of Erk1/2 activation by osteopontin in PC3 human prostate cancer cells
Authors: Robertson Brian W , Bonsal Lauren , Chellaiah Meenakshi A
Published: October 2010

Background

Osteopontin (OPN) has been shown to play many roles in the progression of cancer. We have recently demonstrated the activation of Akt by OPN. Integrin-linked kinase and PI3-kinase are integral proteins in OPN/AKT pathway in PC3 cells. To investigate the role of the extracellular receptors in OPN signaling, we have examined the spatio-temporal regulation of CD44 and integrin αvβ3 receptor in OPN-induced Akt activation in PC3 cells.

Results

Here, our studies demonstrate that OPN can activate Akt either through the αVβ3 integrin or the CD44 cell surface receptor. Members of the Mitogen Activated Protein Kinase (MAPK) family have been shown to be up-regulated in a variety of human cancers and have been implicated in the metastatic behavior. Our studies have demonstrated an increase in the phosphorylation of c-Raf at Ser259 and Ser338 in PC3 cells over-expressing OPN. This increase matches up with the Erk1/2 phosphorylation at Thr202/204 and activation. However, the inhibition of Akt activity augments the phosphorylation state of ERK1/2 to two to three fold with a concomitant reduction in the phosphorylation state of c-Raf at Ser259.

Conclusions

Regulation c-Raf phosphorylation at Ser259 has a role in the anti-apoptotic pathways mediated by Akt or Raf/MEK/ERK proteins. OPN may have dual effects in the activation of Erk1/2. We propose this based on the observations that while OPN activates c-Raf and Erk1/2; it also acts to inhibit c-Raf and Erk1/2 activation through Akt pathway. Our observations suggest that the activation of c-Raf-ERK cascade may promote cell cycle arrest in prostate cancer cells and OPN signaling has a role in the anti-apoptotic mechanism.
Association of the LIPG 584C > T polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations
Authors: Liu Wan-Ying , Yin Rui-Xing , Zhang Lin , Cao Xiao-Li , Miao Lin , Wu Dong-Feng , Aung Lynn Htet Htet , Hu Xi-Jiang , Lin Wei-Xiong , Yang De-Zhai
Published: October 2010

Background

Endothelial lipase (EL) is a major determinant of high-density lipoprotein-cholesterol (HDL-C) metabolism, but the association of endothelial lipase gene (LIPG) polymorphism and serum HDL-C levels is scarce and conflicting in diverse populations. Bai Ku Yao is an isolated subgroup of the Yao minority in China. This study was designed to detect the association of LIPG 584C > T (rs2000813) polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.

Methods

A total of 645 subjects of Bai Ku Yao and 638 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of the LIPG 584C > T was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.

Results

The levels of serum total cholesterol (TC), HDL-C, low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (P < 0.05 - 0.001). The frequency of C and T alleles was 73.5% and 26.5% in Bai Ku Yao, and 67.9% and 32.1% in Han (P < 0.01); respectively. The frequency of CC, CT and TT genotypes was 50.4%, 46.2% and 3.4% in Bai Ku Yao, and 41.4%, 53.1% and 5.5% in Han (P < 0.01); respectively. Serum HDL-C levels in both ethnic groups were different among the three genotypes (P < 0.05 for each). Serum TC levels in both ethnic groups were also different between the CC and CT/TT genotypes (P < 0.05 for each). The T allele carriers had higher serum HDL-C and TC levels than the T allele noncarriers. Multivariate logistic regression analysis showed that the levels of HDL-C and ApoB were correlated with genotypes in Bai Ku Yao (P < 0.05 for each), whereas the levels of TC and HDL-C were associated with genotypes in Han Chinese (P < 0.05 and P < 0.01). Serum lipid parameters were also correlated with several environmental factors in the both ethnic groups.

Conclusions

The frequency of LIPG 584T allele is lower in Bai Ku Yao than in Han Chinese. The LIPG 584T allele is associated with increased serum HDL-C, TC and ApoB levels. The differences in serum HDL-C, TC and ApoB levels between the two ethnic groups might partly result from different genotypic and allelic frequencies of LIPG 584C > T or different LIPG-enviromental interactions.
Biophysical analysis of HTLV-1 particles reveals novel insights into particle morphology and Gag stoichiometry
Authors: Grigsby Iwen F , Zhang Wei , Johnson Jolene L , Fogarty Keir H , Chen Yan , Rawson Jonathan M , Crosby Aaron J , Mueller Joachim D , Mansky Louis M
Published: October 2010

Background

Human T-lymphotropic virus type 1 (HTLV-1) is an important human retrovirus that is a cause of adult T-cell leukemia/lymphoma. While an important human pathogen, the details regarding virus replication cycle, including the nature of HTLV-1 particles, remain largely unknown due to the difficulties in propagating the virus in tissue culture. In this study, we created a codon-optimized HTLV-1 Gag fused to an EYFP reporter as a model system to quantitatively analyze HTLV-1 particles released from producer cells.

Results

The codon-optimized Gag led to a dramatic and highly robust level of Gag expression as well as virus-like particle (VLP) production. The robust level of particle production overcomes previous technical difficulties with authentic particles and allowed for detailed analysis of particle architecture using two novel methodologies. We quantitatively measured the diameter and morphology of HTLV-1 VLPs in their native, hydrated state using cryo-transmission electron microscopy (cryo-TEM). Furthermore, we were able to determine HTLV-1 Gag stoichiometry as well as particle size with the novel biophysical technique of fluorescence fluctuation spectroscopy (FFS). The average HTLV-1 particle diameter determined by cryo-TEM and FFS was 71 ± 20 nm and 75 ± 4 nm, respectively. These values are significantly smaller than previous estimates made of HTLV-1 particles by negative staining TEM. Furthermore, cryo-TEM reveals that the majority of HTLV-1 VLPs lacks an ordered structure of the Gag lattice, suggesting that the HTLV-1 Gag shell is very likely to be organized differently compared to that observed with HIV-1 Gag in immature particles. This conclusion is supported by our observation that the average copy number of HTLV-1 Gag per particle is estimated to be 510 based on FFS, which is significantly lower than that found for HIV-1 immature virions.

Conclusions

In summary, our studies represent the first quantitative biophysical analysis of HTLV-1-like particles and reveal novel insights into particle morphology and Gag stochiometry.
GPI-anchored single chain Fv - an effective way to capture transiently-exposed neutralization epitopes on HIV-1 envelope spike
Authors: Wen Michael , Arora Reetakshi , Wang Huiqiang , Liu Lihong , Kimata Jason T , Zhou Paul
Published: October 2010

Background

Identification of broad neutralization epitopes in HIV-1 envelope spikes is paramount for HIV-1 vaccine development. A few broad neutralization epitopes identified so far are present on the surface of native HIV-1 envelope spikes whose recognition by antibodies does not depend on conformational changes of the envelope spikes. However, HIV-1 envelope spikes also contain transiently-exposed neutralization epitopes, which are more difficult to identify.

Results

In this study, we constructed single chain Fvs (scFvs) derived from seven human monoclonal antibodies and genetically linked them with or without a glycosyl-phosphatidylinositol (GPI) attachment signal. We show that with a GPI attachment signal the scFvs are targeted to lipid rafts of plasma membranes. In addition, we demonstrate that four of the GPI-anchored scFvs, but not their secreted counterparts, neutralize HIV-1 with various degrees of breadth and potency. Among them, GPI-anchored scFv (X5) exhibits extremely potent and broad neutralization activity against multiple clades of HIV-1 strains tested. Moreover, we show that GPI-anchored scFv (4E10) also exhibited more potent neutralization activity than its secretory counterpart. Finally, we demonstrate that expression of GPI-anchored scFv (X5) in the lipid raft of plasma membrane of human CD4+ T cells confers long-term resistance to HIV-1 infection, HIV-1 envelope-mediated cell-cell fusion, and the infection of HIV-1 captured and transferred by human DCs.

Conclusions

Thus GPI-anchored scFv could be used as a general and effective way to identify antibodies that react with transiently-exposed neutralization epitopes in envelope proteins of HIV-1 and other enveloped viruses. The GPI-anchored scFv (X5), because of its breadth and potency, should have a great potential to be developed into anti-viral agent for HIV-1 prevention and therapy.
Effects of dihydrocapsiate on adaptive and diet-induced thermogenesis with a high protein very low calorie diet: a randomized control trial
Authors: Lee TszYing Amy , Li Zhaoping , Zerlin Alona , Heber David
Published: October 2010

Background

Dihydrocapsiate (DCT) is a natural safe food ingredient which is structurally related to capsaicin from chili pepper and is found in the non-pungent pepper strain, CH-19 Sweet. It has been shown to elicit the thermogenic effects of capsaicin but without its gastrointestinal side effects.

Methods

The present study was designed to examine the effects of DCT on both adaptive thermogenesis as the result of caloric restriction with a high protein very low calorie diet (VLCD) and to determine whether DCT would increase post-prandial energy expenditure (PPEE) in response to a 400 kcal/60 g protein liquid test meal. Thirty-three subjects completed an outpatient very low calorie diet (800 kcal/day providing 120 g/day protein) over 4 weeks and were randomly assigned to receive either DCT capsules three times per day (3 mg or 9 mg) or placebo. At baseline and 4 weeks, fasting basal metabolic rate and PPEE were measured in a metabolic hood and fat free mass (FFM) determined using displacement plethysmography (BOD POD).

Results

PPEE normalized to FFM was increased significantly in subjects receiving 9 mg/day DCT by comparison to placebo (p < 0.05), but decreases in resting metabolic rate were not affected. Respiratory quotient (RQ) increased by 0.04 in the placebo group (p < 0.05) at end of the 4 weeks, but did not change in groups receiving DCT.

Conclusions

These data provide evidence for postprandial increases in thermogenesis and fat oxidation secondary to administration of dihydrocapsiate.

Trial registration

clinicaltrial.govNCT01142687
Regulation of Hip1r by epsin controls the temporal and spatial coupling of actin filaments to clathrin-coated pits
Authors: Brady Rebecca J. , Damer Cynthia K. , Heuser John E. , O'Halloran Theresa J.
Published: October 2010

Recently, it has become clear that the actin cytoskeleton is involved in clathrin-mediated endocytosis. During clathrin-mediated endocytosis, clathrin triskelions and adaptor proteins assemble into lattices, forming clathrin-coated pits. These coated pits invaginate and detach from the membrane, a process that requires dynamic actin polymerization. We found an unexpected role for the clathrin adaptor epsin in regulating actin dynamics during this late stage of coated vesicle formation. In Dictyostelium cells, epsin is required for both the membrane recruitment and phosphorylation of the actin- and clathrin-binding protein Hip1r. Epsin-null and Hip1r-null cells exhibit deficiencies in the timing and organization of actin filaments at clathrin-coated pits. Consequently, clathrin structures persist on the membranes of epsin and Hip1r mutants and the internalization of clathrin structures is delayed. We conclude that epsin works with Hip1r to regulate actin dynamics by controlling the spatial and temporal coupling of actin filaments to clathrin-coated pits. Specific residues in the ENTH domain of epsin that are required for the membrane recruitment and phosphorylation of Hip1r are also required for normal actin and clathrin dynamics at the plasma membrane. We propose that epsin promotes the membrane recruitment and phosphorylation of Hip1r, which in turn regulates actin polymerization at clathrin-coated pits.
The cargo-selective retromer complex is a recruiting hub for protein complexes that regulate endosomal tubule dynamics
Authors: Harbour Michael E. , Breusegem Sophia Y. A. , Antrobus Robin , Freeman Caroline , Reid Evan , Seaman Matthew N. J.
Published: October 2010

The retromer complex is required for the efficient endosome-to-Golgi retrieval of the CIMPR, sortilin, SORL1, wntless and other physiologically important membrane proteins. Retromer comprises two protein complexes that act together in endosome-to-Golgi retrieval; the cargo-selective complex is a trimer of VPS35, VPS29 and VPS26 that sorts cargo into tubules for retrieval to the Golgi. Tubules are produced by the oligomerization of sorting nexin dimers. Here, we report the identification of five endosomally-localised proteins that modulate tubule formation and are recruited to the membrane via interactions with the cargo-selective retromer complex. One of the retromer-interacting proteins, strumpellin, is mutated in hereditary spastic paraplegia, a progressive length-dependent axonopathy. Here, we show that strumpellin regulates endosomal tubules as part of a protein complex with three other proteins that include WASH1, an actin-nucleating promoting factor. Therefore, in addition to a direct role in endosome-to-Golgi retrieval, the cargo-selective retromer complex also acts as a platform for recruiting physiologically important proteins to endosomal membranes that regulate membrane tubule dynamics.
Optimizing Helicopter Transport of Oil Rig Crews at Petrobras
Authors: Menezes Fernanda , Porto Oscar , Reis Marcelo L. , Moreno Lorenza , Aragão Marcus Poggi de , Uchoa Eduardo , Abeledo Hernán , Nascimento Nelci Carvalho do
Published: October 2010

Petrobras produces nearly 90 percent of Brazil's oil at about 80 offshore oil platforms. It transports approximately 1,900 employees daily between these platforms and four mainland bases, using more than 40 helicopters that vary in capacity, operating costs, and performance characteristics. Each day, flight planners must select the helicopter routes and schedules that satisfy passenger demands. We developed a system that requires less than one hour to generate optimized flight plans that meet operational guidelines, improve travel safety, and minimize operating costs. By using this system, Petrobras reduced its number of offshore landings by 18 percent, total flight time by 8 percent, and flight costs by 14 percent, resulting in annual savings of more than $20 million. Our optimization model is a large-scale mixed integer program that generalizes prior helicopter routing models. We designed a column-generation algorithm that exploits the problem structure to overcome its computational difficulties. As part of the solution method, we use a network flow model to optimally assign passengers to selected routes.
Teaching Note—Spreadsheet Modeling to Determine the Optimum Hotel Room Rate for a Short High-Demand Period
Authors: Leong Thin-Yin , Lee Wee-Leong
Published: October 2010

In this article, we describe a business modeling exercise that helps students understand the complex relationship between demand and price. The exercise seeks to determine the optimum pricing, in view of anticipated occupancy response that maximises profit for a hotel. Through the exercise, students are introduced to advanced Excel operations such as Goal Seek and Solver. This exercise goes through a systematic series of basic modeling steps, starting from identifying input variables and performance measures, and building from a basic model to a final model with sufficient complexity to represent reality. A problem commonly encountered when modeling real-world problems is the lack of complete information; often, information has to be inferred from what little is available from the past. This is demonstrated in developing the hotel occupancy and rate relationship. To ensure the model is robust, we show how trade-off and sensitivity analyses can be conducted.
Service Engineering: Data-Based Course Development and Teaching
Authors: Mandelbaum Avishai , Zeltyn Sergey
Published: October 2010

In this exposition, we discuss empirically based teaching in the newly emerging field of “service engineering.” Specifically, we survey a service engineering course, taught at the Technion–Israel Institute of Technology. The course was “born” about 15 years ago as a graduate seminar and ultimately took its present form as a core course for the undergraduate program in industrial engineering and management. The role of measurements and data as teaching-enhancers and research-drivers is underscored. In addition, we emphasize that data granularity must reach the individual-transaction level. We describe customized databases and software tools that facilitate operational and statistical analysis of services; this includes the use of SEEStat, a data-user interface that was developed at the Technion's SEE Laboratory, for research and educational purposes. Some unique aspects of the course are the incorporation of state-of-the-art research and real-world data in lectures, recitations, and home assignments, as amply presented throughout this work. The application focus of the surveyed course has been telephone call centers, which constitute an explosively growing branch of the service industry. The course is now expanding to also cover healthcare, especially hospitals; some examples from other service areas (e.g., the justice system) are described as well.
DTaP-Tdap Mix-ups in ISMP Medication Errors Reporting: Program Now Involve Hundreds of Patients: Postproduction Intravenous Admixture Checks Less than Ideal: Air Embolism Risk with Pressurized Sprayers: Acetaminophen Study Yields Worrisome Results
Authors: Cohen Michael R. , Smetzer Judy L.
Published: October 2010

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs.

Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below.

Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
Potential Risk of Medication Discrepancies and Reconciliation Errors at Admission and Discharge from an Inpatient Medical Service
Authors: Climente-Martí Mónica , García-Mañón Elda R , Artero-Mora Arturo , Jiménez-Torres N Víctor
Published: October 2010

Background:

Medication discrepancies, defined as unexplained variations among drug regimens at care transitions, are common. Some are unintended and cause reconciliation errors that are potentially detrimental for patients.

Objective:

To determine the prevalence of medication discrepancies and reconciliation errors at admission and discharge in hospitalized patients and explore risk factors for reconciliation errors and their potential clinical impact.

Methods:

An observational prospective study was conducted at a general teaching hospital. Patients who were admitted to the internal medicine service and were receiving chronic preadmission treatment were included in the study. Preadmission treatment was compared with the treatment prescribed on admission (first 48 hours) and at hospital discharge, and discrepancies and reconciliation errors were identified. The primary endpoint was the presence of reconciliation errors at admission and/or discharge. Potential risk factors (patient-, medication-, and system-related) for reconciliation errors were analyzed using a multivariate logistic regression model.

Results:

Of the 120 patients enrolled in the study between April and August 2009, 109 (90.8%) showed 513 discrepancies. The prevalence of patients with reconciliation errors was 20.8% (95% CI 13.6 to 28.1). Intended medication discrepancies were more frequent at admission (96.6%) than at discharge (75.5%), while reconciliation errors were more frequent at discharge (24.5%) than at admission (3.4%). The prevalence ratio (admission vs discharge) was 2.4 (95% CI 1.9 to 3.0) for discrepancies and 0.65 (95% CI 0.32 to 1.32) for reconciliation errors. The logistic regression analysis revealed an association between the number of discrepancies at admission (OR 1.21; 95% CI 1.01 to 1.44) and age (OR 1.05; 95% CI 0.99 to 1.10) and an increased risk of reconciliation errors.

Conclusions:

Medication reconciliation strategies should focus primarily on avoiding errors at discharge. Since medication discrepancies at admission may predispose patients to reconciliation errors, early detection of such discrepancies would logically reduce the risk of reconciliation errors. Medication reconciliation programs must implement a process for gathering accurate preadmission drug histories and must submit this information to a critical assessment of patients' needs.
Autoregressive-Model-Based Fluorescence-Lifetime Measurements by Phase-Modulation Fluorometry Using a Pulsed-Excitation Light Source and a High-Gain Photomultiplier Tube
Authors: Iwata Tetsuo , Ito Ritsuki , Mizutani Yasuhiro , Araki Tsutomu
Published: October 2010

We propose a novel method for measuring fluorescence lifetimes by use of a pulsed-excitation light source and an ordinary or a high-gain photomultiplier tube (PMT) with a high-load resistor. In order to obtain the values of fluorescence lifetimes, we adopt a normal data-processing procedure used in phase-modulation fluorometry. We apply an autoregressive (AR)-model-based data-analysis technique to fluorescence- and reference-response time-series data obtained from the PMT in order to derive plural values of phase differences at a repetition frequency of the pulsed-excitation light source and its harmonic ones. The connection of the high-load resistor enhances sensitivity in signal detection in a certain condition. Introduction of the AR-model-based data-analysis technique improves precision in estimating the values of fluorescence lifetimes. Depending on the value of the load resistor and that of the repetition frequency, plural values of fluorescence lifetimes are obtained at one time by utilizing the phase information of harmonic frequencies. Because the proposed measurement system is simple to construct, it might be effective when we need to know approximate values of fluorescence lifetimes readily, such as in the field of biochemistry for a screening purpose.