bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrition Challenges in a Patient With Sinusoidal Obstructive Syndrome Following an Allogeneic Stem Cell Transplant
Authors: Ringo Kristin , Chen Louise
Published: August 2012

Nutrition management of patients undergoing a hematopoietic stem cell transplant (HSCT) can be challenging. Fluid, macronutrient, and micronutrient needs are often altered due to a variety of therapy‐associated complications and changes in metabolism. Sinusoidal obstructive syndrome (SOS) is a complication characterized by fluid retention, ascites, and painful hepatomegaly that may complicate provision of adequate nutrition to HSCT patients. The nutrition implications and interventions in a patient who developed SOS following an allogeneic matched unrelated donor (Allo/MUD) HSCT are reviewed in the case report.
A scoping review of qualitative studies about children experiencing parental separation
Authors: Birnbaum Rachel , Saini Michael
Published: August 2012

This article explores a scoping review of qualitative studies about children’s experiences and feelings during times of parental separation. The purpose of the review was to explore children’s feelings and attitudes about their parents’ separation and how their voices are heard during times of parental separation. The scoping review examined 44 studies in 13 countries involving 1525 children. While the studies examine how and why children’s voices are important in the decision-making process adults typically remain the gatekeepers of their voices. Children’s participation in child custody decision-making must include them at all levels of practice, policy and research.
Syntheses of novel benzoxazines having vinyl groups and thermal properties of the thermosets
Authors: Takeichi Tsutomu , Thongpradith Soulideth , Hirai Shoko , Takiguchi Tomomi , Kawauchi Takehiro
Published: August 2012

Novel benzoxazines having vinyl groups were synthesized from phenol or bisphenol A, 3- or 4-vinylaniline and paraformaldehyde. The chemical structures of the monomers were confirmed by Fourier transform infrared and 1H-NMR analyses. The polymerization behavior of the monomers was monitored by differential scanning calorimetry. Exothermic peak of the monomers appeared in the range of 219–252 °C, due to the chain polymerization of the vinyl group and the ring-opening polymerization of benzoxazine occurring at the same temperature range. The thermal cure of the monomers afforded polybenzoxazines that have higher thermal properties than those from typical benzoxazines without vinyl groups. For example, glass transition temperature ( Tg) increased for 40 to 100 °C by the introduction of vinyl groups, the highest Tg being observed at 290 °C. The 5% weight loss temperature determined by thermogravimetric analysis also increased by the introduction of vinyl groups.
Climatic control of the biomass-burning decline in the Americas after ad 1500
Authors: Power MJ , Mayle FE , Bartlein PJ , Marlon JR , Anderson RS , Behling H , Brown KJ , Carcaillet C , Colombaroli D , Gavin DG , Hallett DJ , Horn SP , Kennedy LM , Lane CS , Long CJ , Moreno PI , Paitre C , Robinson G , Taylor Z , Walsh MK
Published: August 2012

The significance and cause of the decline in biomass burning across the Americas after ad 1500 is a topic of considerable debate. We synthesized charcoal records (a proxy for biomass burning) from the Americas and from the remainder of the globe over the past 2000 years, and compared these with paleoclimatic records and population reconstructions. A distinct post-ad 1500 decrease in biomass burning is evident, not only in the Americas, but also globally, and both are similar in duration and timing to ‘Little Ice Age’ climate change. There is temporal and spatial variability in the expression of the biomass-burning decline across the Americas but, at a regional–continental scale, ‘Little Ice Age’ climate change was likely more important than indigenous population collapse in driving this decline.
The effect of CYP1A1, GSTT1 and GSTM1 polymorphisms on the risk of lung cancer
Authors: Atinkaya Cansel , Taspinar Mehmet , Sakiragaoglu Onur , Oz Gurhan , Yazici Ulku , Oztuna Derya , Tastepe Irfan , Sunguroglu Asuman
Published: August 2012

Lung cancer, which is mainly affected by environmental factors, is a lethal malignancy. It is also important to investigate the effect of genetic factors on lung cancer aetiology. In this study, we aimed to investigate the distribution of CYP1A1*2C, GSTT1 and GSTM1 polymorphisms in Turkish lung cancer patients to determine whether any promoting effect of polymorphisms could cause development of lung cancer. For this purpose, genomic DNA samples obtained from peripheral blood of 128 patients with lung cancer and 122 healthy subjects were analyzed. Genotyping of polymorphic enzymes were carried out by polymerase chain reaction–restriction fragment length polymorphism methods. Although there were no significant differences between groups in terms of CYP1A1 polymorphism, the carriers of CYP1A1 Ile/Val genotype (odds ratio [OR] = 1.224, 95% confidence interval [CI]: 0.585–2.564) or CYP1A1 Val/Val genotype (OR = 3.058, 95% CI: 0.312–30.303) had an increased risk of lung cancer development. There was no statistical difference between groups in terms of both GSTT1 null genotype (OR = 1.114, 95% CI: 0.590–2.105) and GSTM1 null genotype (OR = 0.776, 95% CI: 0.466–1.290). This is the first case–control study investigating CYP1A1 Ile/Val, GSTT1 and GSTM1 polymorphisms in Turkish lung cancer patients. Although we suggest that other genes in addition to the proposed genes could play a role in lung cancer development, the results of our study will contribute to the possible associations between CYP1A1 Ile/Val, GSTT1 and GSTM1 gene polymorphism on the risk of lung cancer.
Citosol (thiamylal sodium) triggers apoptosis and affects gene expressions of murine leukemia RAW 264.7 cells
Authors: Wu RS-C , Yu C-S , Liu K-C , Huang H-Y , Ip S-W , Lin J-P , Chueh F-S , Yang J-S , Chung J-G
Published: August 2012

Citosol (thiamylal sodium) is one of generally used anesthetic–sedative agents for clinical patients, and it has not been reported to show induction of cytotoxic effects in cancer cells, especially in mice leukemia RAW 264.7 cells in vitro. In the present study, we investigated the cytotoxic effects of citosol on mice leukemic RAW 264.7 cells, including the effects on protein and gene expression levels which are determined by Western blotting and DNA microarray methods, respectively. Results indicated that citosol induced cell morphological changes, cytotoxic effect, and induction of apoptosis in RAW 264.7 cells. Western blotting analysis demonstrated that citosol promoted the levels of Fas, cytochrome c, caspase 9 and 3 active form and Bax levels, but it suppressed Bcl-xl protein level that may lead to apoptotic death in RAW 264.7 cells. Furthermore, DNA microarray assay indicated that citosol significantly promoted the expression of 5 genes (Gm4884, Gm10883, Lce1c, Lrg1, and LOC100045878) and significantly inhibited the expression of 24 genes (Gm10679, Zfp617, LOC621831, Gm5929, Snord116, Gm3994, LOC380994, Gm5592, LOC380994, LOC280487, Gm4638, Tex24, A530064D06Rik, BC094916, EG668725, Gm189, Hist2h3c2, Gm8020, Snord115, Gm3079, Olfr198, Tdh, Snord115, and Olfr1249). Based on these observations, citosol induced cell apoptosis and influenced gene expression in mice leukemia RAW 264.7 cells in vitro.
A significant dose-dependent relationship between mercury exposure from dental amalgams and kidney integrity biomarkers
Authors: Geier DA , Carmody T , Kern JK , King PG , Geier MR
Published: August 2012

Dental amalgams are a commonly used dental restorative material. Amalgams are about 50% mercury (Hg), and Hg is known to significantly accumulate in the kidney. It was hypothesized that because Hg accumulates in the proximal tubules (PTs), glutathione- S-transferases (GST)-α (suggestive of kidney damage at the level of PT) would be expected to be more related to Hg exposure than GST-π (suggestive of kidney damage at the level of the distal tubules). Urinary biomarkers of kidney integrity were examined in children of 8–18 years old, with and without dental amalgam fillings, from a completed clinical trial (parent study). Our study determined whether there was a significant dose-dependent correlation between increasing Hg exposure from dental amalgams and GST-α and GST-π as biomarkers of kidney integrity. Overall, the present study, using a different and more sensitive statistical model than the parent study, revealed a statistically significant dose-dependent correlation between cumulative exposure to Hg from dental amalgams and urinary levels of GST-α, after covariate adjustment; where as, a nonsignificant relationship was observed with urinary levels of GST-π. Furthermore, it was observed that urinary GST-α levels increased by about 10% over the 8-year course of the study among individuals with an average exposure to amalgams among the study subjects from the amalgam group, in comparison with study subjects with no exposure to dental amalgams. The results of our study suggest that dental amalgams contribute to ongoing kidney damage at the level of the PTs in a dose-dependent fashion.
Application of response surface methodology for optimization of ionic liquid-based dispersive liquid–liquid microextraction of cadmium from water samples
Authors: Rajabi M , Kamalabadi M , Jamali MR , Zolgharnein J , Asanjarani N
Published: August 2012

A new, rapid, and simple method for the determination of cadmium in water samples was developed using ionic liquid-based dispersive liquid–liquid microextraction (IL-DLLME) coupled to flame atomic absorption spectrometry (FAAS). In the proposed approach, 2-(5-boromo-2-pyridylazo)-5-(diethyamino) phenol was used as a chelating agent and 1-hexyl-3-methylimidazolium bis(trifluoro methylsulfonyl)imide and acetone were selected as extraction and dispersive solvents, respectively. Sample pH, concentration of chelating agent, amount of ionic liquid (extraction solvent), disperser solvent volume, extraction time, salt effect, and centrifugation speed were selected as interested variables in IL-DLLME process. The significant variables affecting the extraction efficiency were determined using a Placket–Burman design. Thereafter, the significant variables were optimized using a Box–Behnken design and the quadratic model between the dependent and the independent variables was built. The optimum experimental conditions obtained from this statistical evaluation included: pH: 6.7; concentration of chelating agent: 1.1 × 10−3 mol L−1; and ionic liquid: 50.0 mg. Under the optimum conditions, the preconcentration factor obtained was 100. Calibration graph was linear in the range of 0.2–60 µg L−1 with correlation coefficient of 0.9992. The limit of detection was 0.06 µg L−1, which is lower than other reported approaches applied to the determination of cadmium using FAAS. The relative SD ( n = 8) was 2.4%. The proposed method was successfully applied to the determination of trace amounts of cadmium in the real water samples with satisfactory results.
A contemporary case series of lupus myocarditis
Authors: Zawadowski GM , Klarich KW , Moder KG , Edwards WD , Cooper LT
Published: August 2012

Objectives: The purpose of this study was to describe clinical phenotype and treatment outcomes in lupus myocarditis (LM), an uncommon but serious manifestation of systemic lupus erythematosus (SLE). Methods: The study involved a 10-year retrospective case series of hospitalized patients with LM, with a search of a diagnosis database using systemic lupus erythematosus and either myocarditis, cardiomyopathy, or congestive heart failure, and of a pathology database for biopsy-proved LM. Results: Twenty-four patients met the study criteria, with 79% female and 82% white (age: mean (SD), 47.6 (20.4) years; follow-up: mean (SD), 9.2 (6.1) months). The frequency of antibodies SS-A (69%) and anti-RNP (62%) was greater than in published lupus populations (25%–40%). On echocardiography, the mean initial left ventricular ejection fraction was 33.8%, improving to 49.5% after a mean of 7.2 months. All patients received immunosuppression, most with high-dose corticosteroid treatment and subsequent corticosteroid taper. One patient died of cardiogenic shock during hospitalization; two patients died within one year posthospitalization. Conclusions: A high index of suspicion is necessary in suspected LM. Higher frequency of elevated SS-A and anti-RNP antibody levels in our series than in the literature is suggestive of an LM association. Echocardiography is a useful initial investigation for LM, but patients should be referred early for cardiac magnetic resonance imaging or endomyocardial biopsy to confirm diagnosis if it is clinically indicated in difficult cases.
Passive multi-source energy harvesting schemes
Authors: Schlichting Alexander , Tiwari Rashi , Garcia Ephrahim
Published: August 2012

Mobile electronics have continually decreased in size; however, mobile power sources have not had comparable increases in energy density or specific energy. Researchers are considering energy harvesting technologies to reduce dependence on batteries, providing alternate sources of power. Combining multiple energy harvesters onto a single platform is a logical and practical method to increase energy output and system robustness. This study explored the dynamics of two passive, multi-source energy harvesting schemes: disparate sources of piezoelectric and photovoltaic, as well as an array of piezoelectrics. A series and a parallel topology were explored for each scheme. For both the schemes, the series topology lends itself to high-level, low-duty cycle load characteristics as it is able to achieve greater amounts of energy on a storage capacitor. The parallel topology lends itself to low-level, high-duty cycle load characteristics due to increased maximum power levels. Both the parallel and the series topologies of the array of piezoelectrics effectively combine the power from the two harvesters in the absence of differences between the two signals. The series topology is insensitive to amplitude differences, and the parallel topology is insensitive to a phase angle or a frequency difference.
Fatigue damage prediction of cruciform specimen under biaxial loading
Authors: Luo Chuntao , Mohanty Subhasish , Chattopadhyay Aditi
Published: August 2012

This article investigates an energy-based multiscale damage criterion for a biaxial loading case. The criterion incorporates crystal plasticity at the microscale that produces a damage tensor, representing the local damage state derived from a least squares method. The damage tensor, driven by modification of strain energy density on each potential slip system, is averaged from local to grain level to obtain a damage vector for each grain. The Kreisselmeier–Steinhauser function, which produces an envelope function for multiobjective optimization is adopted to predict the failure of a meso–representative volume element, and to calculate the damage index for meso–representative volume element. A weighted averaging method is also used to simultaneously provide the most potential cracking directions for meso–representative volume element. In order to verify that the developed method is capable of producing an acceptable prediction of fatigue damage initiation and growth under multiaxial loading conditions, a cruciform specimen is used for biaxial loading. A biaxial torsion MTS machine is used to conduct fatigue tests on the cruciform specimen. Numerical fatigue analysis is also performed based on the multiscale fatigue damage criterion. Comparing the simulation results with the experimental data shows that the multiscale fatigue damage model can provide acceptable prediction of failure of meso–representative volume element and crack direction.
Early Interventionists’ Perspectives on Teaching Caregivers
Authors: Sawyer Brook E. , Campbell Philippa H.
Published: August 2012

Relatively little is known about the role of early interventionists as teachers of caregivers. The current study was conducted to better understand interventionists’ perspectives about teaching caregivers. A national sample of 1,525 multidisciplinary interventionists completed an online questionnaire, which elicited information about interventionists’ preferences for use of caregiver teaching strategies, factors influencing decisions about teaching strategy use as well as comfort in, frequency of, and barriers to teaching caregivers. Use of a range of teaching strategies across contexts was reported. Differences emerged in teaching strategy preference based on experience in teaching specific skills and years of experience in early intervention. Ten themes emerged as rationales for teaching strategy selection. Interventionists reported moderate confidence in and frequency of caregiver teaching and few barriers to teaching. Results suggest a preference for use of multiple strategies and selection factors based on experience, perceived caregiver benefit, or other general factors such as interventionist preference.
Measurements of lubrication characteristics of a tilting pad thrust bearing disturbed by a water-contaminated lubricant
Authors: Harika Elias , Bouyer Jean , Fillon Michel , Hélène Mathieu
Published: August 2012

The effect of water contamination on the lubrication has been described in several studies. Water has been defined as a dangerous contaminant which has a very detrimental impact on bearing performance. Nevertheless, many of the previous studies are based on post-accidental analyses, made after the lubrication failure. Thus, these analyses do not take into account all the possible conditions of the presence of water in the oil that can describe the situation. For instance, the case of water-in-oil fine emulsion has never been considered neither the experimental study of the water effect in the case of bearings. Experiments presented in this study were carried out on an eight shoes tilting pad thrust bearing supplied with water-contaminated oil. The contamination rate reached 10% of water by mass while the mixture was a water-in-oil emulsion. Results show that the presence of water is not such detrimental as could have been expected for the cases studied and moreover, that the bearing could have an enhanced behaviour while operating with the presence of water in the oil.
Parliamentary party cohesion
Authors: Russell Meg
Published: August 2012

High levels of party voting cohesion are common in modern legislatures. Current explanations divide into sociological (based on norms and roles) and rational choice (based on systems of punishment and reward). The latter approach dominates, but cannot explain cohesion in systems with weak disciplinary sanctions, such as the British House of Lords. Social psychology has provided a great deal of insight into conformity in groups, but this has rarely been deployed in studying parties. Neuroscience now also allows us better to understand the physiological mechanisms underlying responses such as need to belong and fear of ostracism. This article outlines key theories and findings from psychology relevant to parliamentary party cohesion, and then explores these using survey data from the relatively ‘discipline free’ House of Lords. It is suggested that psychological factors such as social identity are important to the operation of party groups, and stronger interdisciplinary links are proposed between political science and psychology.
Psychopharmacology of autism spectrum disorders: A selective review
Authors: Mohiuddin Sarah , Ghaziuddin Mohammad
Published: August 2012

While there is no cure for autism spectrum disorder, psychopharmacologic agents are often used with behavioral and educational approaches to treat its comorbid symptoms of hyperactivity, irritability, and aggression. Studies suggest that at least 50% of persons with autism spectrum disorder receive psychotropic medications during their life span. This selective review examines recent studies about the use of psychotropic medications in persons with autism spectrum disorder. The aim was to focus on randomized controlled trials conducted from 1990 to 2010 on this topic. A comprehensive literature search was performed using PubMed and Cochrane databases. Out of 105 studies identified for the review, only 24 were randomized controlled trials. Thus, despite the common use of these medications in autism spectrum disorder, more controlled studies are needed to determine their long-term efficacy and safety.
Agitation and Psychosis Associated With Dementia With Lewy Bodies Exacerbated by Modafinil Use
Authors: Prado Eduardo , Paholpak Pongsatorn , Ngo Myha , Porter Verna , Apostolova Liana G. , Marrocos Rogério , Ringman John M.
Published: August 2012

Dementia with Lewy bodies (DLB) is commonly associated with excessive daytime somnolence (EDS). Modafinil is a wakefulness-promoting agent that is considered to have limited interaction with the dopaminergic system. As individuals with DLB are predisposed to psychotic symptoms that might be exacerbated by dopaminergic stimulation, modafinil is considered to be an attractive option for the treatment of EDS in DLB. We describe 2 cases in which administration of modafinil exacerbated agitation and hallucinations in DLB, and we also review data that may explain the mechanisms underlying this effect. In both cases, psychotic symptoms emerged concomitantly with modafinil administration and remitted following its discontinuation. Although definitive data regarding the benefits and adverse effects of modafinil for the treatment of EDS in DLB await controlled prospective randomized studies, our observations warrant caution regarding its use in this context.
Pay Equity as a Mediator of the Relationships Among Attitudes and Communication About Pay Level Determination and Pay Secrecy
Authors: Day Nancy E.
Published: August 2012

Although a limited amount of research exists on pay communication, most shows that pay communication is associated with positive attitudes. Little research exists on pay secrecy and its outcomes. Using equity theory, this article explores the dynamics of how perceived pay communication and perceived pay secrecy policies relate to desirable attitudes. The article proposes that pay equity is the link that mediates these relationships. Data were collected in a U.S. public utility, and findings reveal that perceived communication about how pay levels are determined is positively associated with affective organizational commitment and three dimensions of pay satisfaction, and most of these relationships are fully or partially mediated by pay equity. While perceived written pay secrecy policies show no relationship with attitudes, perceived unwritten secrecy policies negatively predict pay administration satisfaction and this relationship is mediated by pay equity. Finally, neither written nor unwritten pay secrecy policies are related to whether or not respondents report discussing their pay.
From Ethnography to Items
Authors: Crede Erin , Borrego Maura
Published: August 2012

As part of a sequential exploratory mixed methods study, 9 months of ethnographically guided observations and interviews were used to develop a survey examining graduate engineering student retention. Findings from the ethnographic fieldwork yielded several themes, including international diversity, research group organization and climate, perception of value, and individual and group learning. In this article, the authors present the final themes from the ethnographic analysis and discuss how these data were configured into constructs and survey questions. The authors discuss the final survey, including validity and reliability analysis, and how constructs were developed to test hypotheses for future studies. The article concludes with implications for mixed methods researchers interested in using qualitative methods to create new surveys.
Effect of massive outer leaf of an insulated cavity brick wall on heat loss
Authors: Lindberg Ralf W , Rantala Jukka V , Leivo Virpi M , Kiviste Mihkel
Published: August 2012

The availability of coherent long-term measured data on climatic variables and building parameters forms the basis for predicting, analyzing, and simulating the heating or cooling energy demand on buildings. This article analyzes measured 4-year data considering the test building with an insulated cavity brick wall with a massive outer brick leaf. The results show that the solar radiation and the thermal inertia of massive outer leaf of a wall have a significant effect on the heat loss and energy consumption of the buildings throughout Finland and Scandinavia. Based on the average outdoor air temperatures, the nominal calculated heat losses could be overestimated. For more accurate heat losses, the outdoor surface temperature should be applied as a boundary condition. The measured results were verified with finite element method.
Effects of plerixafor in combination with BCR-ABL kinase inhibition in a murine model of CML
Authors: Agarwal Anupriya , Fleischman Angela G. , Petersen Curtis L. , MacKenzie Ryan , Luty Samuel , Loriaux Marc , Druker Brian J. , Woltjer Randall L. , Deininger Michael W.
Published: August 2012

Sequestration in the bone marrow niche may allow leukemic stem cells to evade exposure to drugs. Because the CXCR4/SDF-1 axis is an important mechanism of leukemic stem cell interaction with marrow stroma, we tested whether plerixafor, an antagonist of CXCR4, may dislodge chronic myeloid leukemia (CML) cells from the niche, sensitizing them to tyrosine kinase inhibitors. We initially treated mice with retrovirally induced CML-like disease with imatinib plus plerixafor. Plerixafor mobilized CXCR4+ cells, but no difference was observed in leukemia burden, possibly reflecting insufficient disease control by imatinib. In a second series of experiments, we tested the combination of plerixafor with dasatinib in the same as well as an attenuated CML model. Despite much improved leukemia control, plerixafor failed to reduce leukemia burden over dasatinib alone. In addition, mice receiving plerixafor had an increased incidence of neurologic symptoms in association with CNS infiltration by BCR-ABL–expressing cells. We conclude that plerixafor is ineffective in reducing leukemia burden in this model but promotes CNS infiltration. Beneficial effects of combining tyrosine kinase inhibitors with plerixafor may be observed in a situation of minimal residual disease, but caution is warranted when disease control is incomplete.
Endogenous HLA class II epitopes that are immunogenic in vivo show distinct behavior toward HLA-DM and its natural inhibitor HLA-DO
Authors: Kremer Anita N. , van der Meijden Edith D. , Honders Maria W. , Goeman Jelle J. , Wiertz Emmanuel J. H. J. , Falkenburg J. H. Frederik , Griffioen Marieke
Published: August 2012

CD4+ T cells play a central role in adaptive immunity. The acknowledgment of their cytolytic effector function and the finding that endogenous antigens can enter the HLA class II processing pathway make CD4+ T cells promising tools for immunotherapy. Expression of HLA class II and endogenous antigen, however, does not always correlate with T-cell recognition. We therefore investigated processing and presentation of endogenous HLA class II epitopes that induced CD4+ T cells during in vivo immune responses. We demonstrate that the peptide editor HLA-DM allowed antigen presentation of some (DM-resistant antigens) but abolished surface expression of other natural HLA class II epitopes (DM-sensitive antigens). DM sensitivity was shown to be epitope specific, mediated via interaction between HLA-DM and the HLA-DR restriction molecule, and reversible by HLA-DO. Because of the restricted expression of HLA-DO, presentation of DM-sensitive antigens was limited to professional antigen-presenting cells, whereas DM-resistant epitopes were expressed on all HLA class II–expressing cells. In conclusion, our data provide novel insights into the presentation of endogenous HLA class II epitopes and identify intracellular antigen processing and presentation as a critical factor for CD4+ T-cell recognition. This opens perspectives to exploit selective processing capacities as a new approach for targeted immunotherapy.
ROCK suppression promotes differentiation and expansion of endothelial cells from embryonic stem cell–derived Flk1+ mesodermal precursor cells
Authors: Joo Hyung Joon , Choi Dong-Kyu , Lim Joon Seo , Park Jin-Sung , Lee Seung-Hun , Song Sukhyun , Shin Jennifer H. , Lim Do-Sun , Kim Injune , Hwang Ki-Chul , Koh Gou Young
Published: August 2012

Successful differentiation and expansion of endothelial cells (ECs) from embryonic stem cell (ESC)–derived Flk1+ mesodermal precursor cells (MPCs) requires supplementation of vascular endothelial growth factor-A (VEGF-A). While analyzing VEGF-A/VEGFR2 downstream signaling pathway that underlies the VEGF-A-induced differentiation and expansion of ECs, we fortuitously found that Rho-associated protein kinase (ROCK) inhibitor Y27632 profoundly promoted the differentiation and expansion of ECs from Flk1+ MPCs while reducing the differentiation and expansion of mural cells. The ROCK suppression-induced expansion of ECs appears to have resulted from promotion of proliferation of ECs via activation of PI3-kinase-Akt signaling. The ECs obtained by the combination of ROCK suppression and VEGF-A supplementation faithfully expressed most pan-EC surface makers, and phenotypic analyses revealed that they were differentiated toward arterial EC. Further incubation of the ICAM2+ ECs with Y27632 and VEGF-A for 2 days promoted expansion of ECs by 6.5-fold compared with those incubated with only VEGF-A. Importantly, the ROCK suppression-induced ECs displayed neovasculogenic abilities in vitro and in vivo. Thus, supplementation of ROCK inhibitor Y27632 along with VEGF-A in 2D Matrigel culture system provides a simple, efficient, and versatile method for obtaining ample amount of ESC-derived ECs at high purity suitable for use in therapeutic neovascularization.
Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial
Authors: Mateos María-Victoria , Oriol Albert , Martínez-López Joaquín , Gutiérrez Norma , Teruel Ana-Isabel , López de la Guía Ana , López Javier , Bengoechea Enrique , Pérez Montserrat , Polo Marta , Palomera Luis , de Arriba Felipe , González Yolanda , Hernández Jose-Mariano , Granell Miquel , Bello José-Luis , Bargay Joan , Peñalver Francisco-Javier , Ribera José-María , Martín-Mateos María-Luisa , García-Sanz Ramón , Lahuerta Juan-José , Bladé Joan , San-Miguel Jesús F.
Published: August 2012

Maintenance therapy has become a hot field in myeloma, and it may be particularly relevant in elderly patients because the major benefit results from the initial therapy. We report the results of a randomized comparison of maintenance with bortezomib plus thalidomide (VT) or prednisone (VP) in 178 elderly untreated myeloma patients who had received 6 induction cycles with bortezomib plus either melphalan and prednisone or thalidomide and prednisone. The complete response (CR) rate increased from 24% after induction up to 42%, higher for VT versus VP (46% vs 39%). Median progression-free survival (PFS) was superior for VT (39 months) compared with VP (32 months) and overall survival (OS) was also longer in VT patients compared with VP (5-year OS of 69% and 50%, respectively) but the differences did not reach statistical significance. CR achievement was associated with a significantly longer PFS (P < .001) and 5-year OS (P < .001). The incidence of G3-4 peripheral neuropathy was 9% for VT and 3% for VP. Unfortunately, this approach was not able to overcome the adverse prognosis of cytogenetic abnormalities. In summary, these maintenance regimens result in a significant increase in CR rate, remarkably long PFS, and acceptable toxicity profile. The trial is registered at www.clinicaltrials.gov as NCT00443235.
B cells from patients with chronic GVHD are activated and primed for survival via BAFF-mediated pathways
Authors: Allen Jessica L. , Fore Matthew S. , Wooten Jenna , Roehrs Philip A. , Bhuiya Nazmim S. , Hoffert Todd , Sharf Andrew , Deal Allison M. , Armistead Paul , Coghill James , Gabriel Don A. , Irons Robert , Essenmacher Amber , Shea Thomas C. , Richards Kristy , Cutler Corey , Ritz Jerome , Serody Jonathan , Baldwin Albert S. , Sarantopoulos Stefanie
Published: August 2012

Recent data reveal an important role for B cells in the pathogenesis of chronic GVHD (cGVHD). Patients with cGVHD have delayed B-cell reconstitution and elevated BAFF to B-cell ratios compared to patients without cGVHD. The mechanisms promoting and sustaining B-cell activation in this disease, however, remain unknown. As BAFF increases murine B-cell metabolism and survival and maintains autoreactive B-cell clones, we performed ex vivo analyses of peripheral B cells from 51 patients who either had or did not have active cGVHD and were greater than 1 year from the time of allogeneic hematopoietic stem cell transplantation. We found that B cells from patients with active cGVHD were in a heightened metabolic state and were resistant to apoptosis. Exogenous BAFF treatment amplified cell size and survival in B cells from these patients. We found significantly increased signaling through ERK and AKT that associated with decreased levels of proapoptotic Bim, suggesting a mechanistic link between elevated BAFF levels and aberrant B-cell survival. Thus, we identify a role for BAFF in the pathogenesis of cGVHD and define B-cell activation and survival pathways suitable for novel therapeutic development in cGVHD.
Inhibitory effects of 405 nm irradiation on Chlamydia trachomatis growth and characterization of the ensuing inflammatory response in HeLa cells
Authors: Wasson Cassandra J , Zourelias Jessica L , Aardsma Nathan A , Eells Janis T , Ganger Mike T , Schober Justine M , Skwor Troy A
Published: August 2012

Background

Chlamydia trachomatis is an intracellular bacterium that resides in the conjunctival and reproductive tract mucosae and is responsible for an array of acute and chronic diseases. A percentage of these infections persist even after use of antibiotics, suggesting the need for alternative treatments. Previous studies have demonstrated anti-bacterial effects using different wavelengths of visible light at varying energy densities, though only against extracellular bacteria. We investigated the effects of visible light (405 and 670 nm) irradiation via light emitting diode (LEDs) on chlamydial growth in endocervical epithelial cells, HeLa, during active and penicillin-induced persistent infections. Furthermore, we analyzed the effect of this photo treatment on the ensuing secretion of IL-6 and CCL2, two pro-inflammatory cytokines that have previously been identified as immunopathologic components associated with trichiasis in vivo.

Results

C. trachomatis-infected HeLa cells were treated with 405 or 670 nm irradiation at varying energy densities (0 – 20 J/cm2). Bacterial growth was assessed by quantitative real-time PCR analyzing the 16S: GAPDH ratio, while cell-free supernatants were examined for IL-6 and monocyte chemoattractant protein-1 (CCL2) production. Our results demonstrated a significant dose-dependent inhibitory effect on chlamydial growth during both active and persistent infections following 405 nm irradiation. Diminished bacterial load corresponded to lower IL-6 concentrations, but was not related to CCL2 levels. In vitro modeling of a persistent C. trachomatis infection induced by penicillin demonstrated significantly elevated IL-6 levels compared to C. trachomatis infection alone, though 405 nm irradiation had a minimal effect on this production.

Conclusion

Together these results identify novel inhibitory effects of 405 nm violet light on the bacterial growth of intracellular bacterium C. trachomatis in vitro, which also coincides with diminished levels of the pro-inflammatory cytokine IL-6.
Dairy calcium intake and lifestyle risk factors for bone loss in hiv-infected and uninfected mediterranean subjects
Authors: Vecchi Valentina Li , Soresi Maurizio , Giannitrapani Lydia , Mazzola Giovanni , La Sala Sara , Tramuto Fabio , Caruso Giuseppe , Colomba Claudia , Mansueto Pasquale , Madonia Simona , Montalto Giuseppe , Di Carlo Paola
Published: August 2012

Background

Despite the reported high prevalence of osteoporosis in the human immunodeficiency virus (HIV)-population, there have been no previous studies examining dairy calcium intake and bone mineral density (BMD) in HIV-subjects.

We assessed the prevalence of low BMD in HIV-infected and uninfected subjects and analyzed the effects of calcium intake, lifestyle and HIV-related risk factors on BMD.

Methods

One hundred and twelve HIV-infected subjects were consecutively enrolled. Seventy- six HIV-uninfected subjects matched for age and sex were enrolled as the control group. The HIV-subjects were interviewed about lifestyle habits and completed a weekly food-frequency questionnaire to estimate calcium intake. HIV-RNA, CD4+ T-cell count and data on antiretroviral therapy were also recorded. Both biochemical bone turnover markers and BMD, assessed by dual-energy radiographic absorptiometry (DXA) were recorded in the HIV-cases and controls. We also calculated the 10-year fracture risks using the WHO FRAX equation.

Results

Osteoporosis prevalence was significantly higher in the HIV-cases than controls (p < 0.05). BMI values were positively correlated with BMD (p < 0.05). Vitamin D levels were lower in the HIV-subjects (p < 0.02). No correlation was found with daily calcium intake.

BMI values were significantly correlated with dairy intake quartiles (p < 0.003). In HIV-subjects, the mean of FRAX score was 1.2 % for hip and 4.7 % for major osteoporotic fractures. On multivariate analysis of the lumbar spine DXA T-score, age (p < 0.005) and HIV/hepatitis C virus co-infection (p < 0.0001) were negatively correlated with BMD, while yogurt intake was a protective predictor of BMD (p < 0.05). In the femur DXA T-score, age (p < 0.01), nadir CD4 + T-cell count < 200 cells/μL (p < 0.05) and drug addiction ( p < 0.0001) were negatively correlated with BMD.

Conclusions

Among the foods rich in calcium, yogurt was a protective predictor of BMD in HIV-subjects. HIV/HCV co-infection, nadir CD4 + T-cell count < 200 cells/μL and drug addiction were independent predictors of severe BMD. Promoting behavioral changes in food intake and lifestyle, aimed at the primary prevention of bone disease in the chronically-infected subjects seems to be essential for implementing medical intervention in these cases.
BAC CGH-array identified specific small-scale genomic imbalances in diploid DMBA-induced rat mammary tumors
Authors: Samuelson Emma , Karlsson Sara , Partheen Karolina , Nilsson Staffan , Szpirer Claude , Behboudi Afrouz
Published: August 2012

Background

Development of breast cancer is a multistage process influenced by hormonal and environmental factors as well as by genetic background. The search for genes underlying this malignancy has recently been highly productive, but the etiology behind this complex disease is still not understood. In studies using animal cancer models, heterogeneity of the genetic background and environmental factors is reduced and thus analysis and identification of genetic aberrations in tumors may become easier. To identify chromosomal regions potentially involved in the initiation and progression of mammary cancer, in the present work we subjected a subset of experimental mammary tumors to cytogenetic and molecular genetic analysis.

Methods

Mammary tumors were induced with DMBA (7,12-dimethylbenz[a]anthrazene) in female rats from the susceptible SPRD-Cu3 strain and from crosses and backcrosses between this strain and the resistant WKY strain. We first produced a general overview of chromosomal aberrations in the tumors using conventional kartyotyping (G-banding) and Comparative Genome Hybridization (CGH) analyses. Particular chromosomal changes were then analyzed in more details using an in-house developed BAC (bacterial artificial chromosome) CGH-array platform.

Results

Tumors appeared to be diploid by conventional karyotyping, however several sub-microscopic chromosome gains or losses in the tumor material were identified by BAC CGH-array analysis. An oncogenetic tree analysis based on the BAC CGH-array data suggested gain of rat chromosome (RNO) band 12q11, loss of RNO5q32 or RNO6q21 as the earliest events in the development of these mammary tumors.

Conclusions

Some of the identified changes appear to be more specific for DMBA-induced mammary tumors and some are similar to those previously reported in ACI rat model for estradiol-induced mammary tumors. The later group of changes is more interesting, since they may represent anomalies that involve genes with a critical role in mammary tumor development. Genetic changes identified in this work are at very small scales and thus may provide a more feasible basis for the identification of the target gene(s). Identification of the genes underlying these chromosome changes can provide new insights to the mechanisms of mammary carcinogenesis.
Hepatitis B virus X protein suppresses caveolin-1 expression in hepatocellular carcinoma by regulating DNA methylation
Authors: Yan Jun , Lu Qian , Dong Jiahong , Li Xiaowu , Ma Kuansheng , Cai Lei
Published: August 2012

Background

To understand the molecular mechanisms of caveolin-1 downregulation by hepatitis B virus X protein (HBx).

Methods

The DNA methylation status of the caveolin-1 promoter was examined by nested methylation-specific PCR of 33 hepatitis B virus (HBV)-infected hepatocellular carcinoma (HCC) samples. The SMMC-7721 hepatoma cell line was transfected with a recombinant HBx adenoviral vector, and the effects of HBx protein on caveolin-1 expression and promoter methylation were examined and confirmed by sequencing. A reporter gene containing the caveolin-1 promoter region was constructed, and the effects of HBx on the transcriptional activity of the promoter were also studied.

Results

Methylation of the caveolin-1 promoter was detected in 84.8% (28/33) of HBV-infected HCC samples. Expression of caveolin-1 was significantly downregulated (P = 0.022), and multiple CpG sites in the promoter region of caveolin-1 were methylated in SMMC-7721 cells after HBx transfection. Transfected HBx significantly suppressed caveolin-1 promoter activity (P = 0.001).

Conclusions

HBx protein induces methylation of the caveolin-1 promoter region and suppresses its expression.
Solar ultraviolet-B radiation and vitamin D: a cross-sectional population-based study using data from the 2007 to 2009 Canadian Health Measures Survey
Authors: Greenfield Jamie A , Park Philip S , Farahani Ellie , Malik Suneil , Vieth Reinhold , McFarlane Norman A , Shepherd Theodore G , Knight Julia A
Published: August 2012

Background

Exposure to solar ultraviolet-B (UV-B) radiation is a major source of vitamin D3. Chemistry climate models project decreases in ground-level solar erythemal UV over the current century. It is unclear what impact this will have on vitamin D status at the population level. The purpose of this study was to measure the association between ground-level solar UV-B and serum concentrations of 25-hydroxyvitamin D (25(OH)D) using a secondary analysis of the 2007 to 2009 Canadian Health Measures Survey (CHMS).

Methods

Blood samples collected from individuals aged 12 to 79 years sampled across Canada were analyzed for 25(OH)D (n = 4,398). Solar UV-B irradiance was calculated for the 15 CHMS collection sites using the Tropospheric Ultraviolet and Visible Radiation Model. Multivariable linear regression was used to evaluate the association between 25(OH)D and solar UV-B adjusted for other predictors and to explore effect modification.

Results

Cumulative solar UV-B irradiance averaged over 91 days (91-day UV-B) prior to blood draw correlated significantly with 25(OH)D. Independent of other predictors, a 1 kJ/m2 increase in 91-day UV-B was associated with a significant 0.5 nmol/L (95% CI 0.3-0.8) increase in mean 25(OH)D (P = 0.0001). The relationship was stronger among younger individuals and those spending more time outdoors. Based on current projections of decreases in ground-level solar UV-B, we predict less than a 1 nmol/L decrease in mean 25(OH)D for the population.

Conclusions

In Canada, cumulative exposure to ambient solar UV-B has a small but significant association with 25(OH)D concentrations. Public health messages to improve vitamin D status should target safe sun exposure with sunscreen use, and also enhanced dietary and supplemental intake and maintenance of a healthy body weight.
Changes of gluteus medius muscle in the adult patients with unilateral developmental dysplasia of the hip
Authors: Liu RuiYu , Wen XiaoDong , Tong ZhiQin , Wang KunZheng , Wang ChunSheng
Published: August 2012

Background

The gluteus medius muscle is essential for gait and hip stability. Changes that occur in the gluteus medius muscles in patients with developmental dysplasia of the hip (DDH) are not well understood. A better understanding of DDH related changes will have positive repercussions toward hip soft tissue reconstruction.

Methods

19 adult patients with unilateral DDH scheduled for total hip arthroplasty were assessed for: cross-sectional area (CSA), radiological density (RD) and the length of gluteus medius using computed tomograhpy(CT) (scanned before THA). Hip abductor moment arm and gluteus medius activation angle were also measuredviahip anteroposterior radiographs.

Results

Both CSA and RD of gluteus medius muscle were significantly reduced (p < 0.05) in the affected hip compared to the control. In the affected hip, the length of the gluteus medius muscle was reduced by 8-11 % (p < 0.05) while the gluteus medius activation angle was significantly increased (p < 0.05) and the hip abductor moment arm was decreased (p < 0.05).

Conclusions

The gluteus medius showed substantial loss of CSA, RD as well as decreased length in patients with DDH in the affected hip. These changes should be considered in both hip reconstruction and postoperative rehabilitation training in patients with DDH.