bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundChildhood 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/DesignThe 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.DiscussionAn 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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
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.
Characterization of the New Serum Protein Reference Material ERM-DA470k/IFCC: Value Assignment by Immunoassay
Authors: Zegers Ingrid , Keller Thomas , Schreiber Wiebke , Sheldon Joanna , Albertini Riccardo , Blirup-Jensen Søren , Johnson Myron , Trapmann Stefanie , Emons Hendrik , Merlini Giampaolo , Schimmel Heinz 
Published: October 2010

BACKGROUNDThe availability of a suitable matrix reference material is essential for standardization of the immunoassays used to measure serum proteins. The earlier serum protein reference material ERM-DA470 (previously called CRM470), certified in 1993, has led to a high degree of harmonization of the measurement results. A new serum protein material has now been prepared and its suitability in term of homogeneity and stability has been verified; after characterization, the material has been certified as ERM-DA470k/IFCC.METHODSWe characterized the candidate reference material for 14 proteins by applying a protocol that is considered to be a reference measurement procedure, by use of optimized immunoassays. ERM-DA470 was used as a calibrant.RESULTSFor 12 proteins [α2 macroglobulin (A2M), α1 acid glycoprotein (orosomucoid, AAG), α1 antitrypsin (α1-protease inhibitor, AAT), albumin (ALB), complement 3c (C3c), complement 4 (C4), haptoglobin (HPT), IgA, IgG, IgM, transferrin (TRF), and transthyretin (TTR)], the results allowed assignment of certified values in ERM-DA470k/IFCC. For CRP, we observed a bias between the lyophilized and liquid frozen materials, and for CER, the distribution of values was too broad. Therefore, these 2 proteins were not certified in the ERM-DA470k/IFCC. Different value transfer procedures were tested (open and closed procedures) and found to provide equivalent results.CONCLUSIONSA new serum protein reference material has been produced, and values have been successfully assigned for 12 proteins.
A novel TMEM127 mutation in a patient with familial bilateral pheochromocytoma
Authors: Burnichon Nelly , Lepoutre-Lussey Charlotte , Laffaire Julien , Gadessaud Noémie , Molinié Vincent , Hernigou Anne , Plouin Pierre-François , Jeunemaitre Xavier , Favier Judith , Gimenez-Roqueplo Anne-Paule 
Published: October 2010

ObjectiveIn this report, we describe a new patient with unexplained familial bilateral pheochromocytoma. Following the recent description of TMEM127 as a new pheochromocytoma susceptibility gene, the aim of this study was to test the hypothesis of a causative TMEM127 gene mutation in this patient.DesignPheochromocytoma susceptibility genes were analyzed in germline DNA and losses of heterozygosity (LOH) assessed by BAC array comparative genomic hybridization in tumor DNA. SDHB expression and S6 kinase (S6K) phosphorylation were analyzed by immunohistochemistry. Genome-wide expression microarray studies were performed, and vascular density was quantified after CD34 immunohistochemistry.ResultsA first germline variant was identified in the SDHB gene (c.158G>A; p.Gly53Glu). However, a positive SDHB immunostaining in the tumor indicated that this SDHB variant was a non-functional polymorphism. A novel TMEM127 germline mutation (c.140C>A, p.Ala47Asp) associated with a 2q11 LOH was found. Transcriptome and immunohistochemical analyses showed that TMEM127-related pheochromocytoma clusterized with NF1-related and RET-related tumors in a large series of pheochromocytomas and paragangliomas, exhibited a reduced TMEM127 mRNA expression and displayed a low vascularization. The phosphorylation of S6K observed in this tumor was suggestive of an activation of the MTOR pathway.ConclusionsPathological and genomic data demonstrated that a TMEM127 gene mutation not previously described was causative of a new case of familial bilateral pheochromocytoma. This report highlights the importance of supplementary analyses on tumor tissue to provide an accurate pheochromocytoma/paraganglioma genetic testing result to affected patients.