bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of back and leg pain with health status and functional capacity of older adults: Findings from the retirement community back pain study
Authors: Hicks Gregory E. , Gaines Jean M. , Shardell Michelle , Simonsick Eleanor M. 
Published: August 2008

AbstractObjectiveLow back pain (LBP) is the most frequently reported musculoskeletal problem in older adults, but its impact on health status is not well understood. Our objective was to determine whether LBP and concurrent leg pain are associated with health‐related quality of life (HRQOL) and function in a cohort of older adults, and to examine care‐seeking behaviors related to LBP.MethodsThis was a population‐based, cross‐sectional survey study of 522 community‐dwelling men and women (67.4%) ages ≥62 living in 4 retirement communities in Maryland and northern Virginia. LBP status in the past year was categorized as no pain in the low back or leg, LBP only, and LBP with leg pain. HRQOL and function were measured with the Medical Outcomes Study Short Form 36 (SF‐36).ResultsA total of 26.8% of the sample reported LBP only and 21.3% reported LBP plus leg pain. Participants with LBP and LBP plus leg pain had lower scores in all SF‐36 domains, reflecting worse HRQOL (P < 0.0001). LBP and LBP plus leg pain were associated with 2‐fold greater odds of falling and increased difficulty lifting grocery bags, walking several blocks, and bathing. LBP plus leg pain was associated with difficulty in social interactions (odds ratio 10.63, 95% confidence interval 3.57–31.60). Less than half sought care for LBP and those who did had poorer health status and greater pain burden.ConclusionLBP is common among older adults and strongly associated with reduced HRQOL and function. These findings argue strongly for both identifying cases of LBP by health care practitioners and pursuing effective treatments for LBP given the potential consequences.
Effect of therapeutic exercise for hip osteoarthritis pain: Results of a meta‐analysis
Authors: Hernández‐Molina Gabriela , Reichenbach Stephan , Zhang Bin , Lavalley Michael , Felson David T. 
Published: August 2008

AbstractObjectiveRecommendations for lower extremity osteoarthritis (OA) and exercise have been primarily based on knee studies. To provide more targeted recommendations for the hip, we gathered evidence for the efficacy of exercise for hip OA from randomized controlled trials.MethodsA bibliographic search identified trials that were randomized, controlled, completed by ≥60% of subjects, and involved an exercise group (strengthening and/or aerobic) versus a nonexercise control group for pain relief in hip OA. Two reviewers independently performed the data extraction and contacted the authors when necessary. Effect sizes (ES) of treatment versus control and the I2statistic to assess heterogeneity across trials were calculated. Trial data were combined using a random‐effects meta‐analysis.ResultsNine trials met the inclusion criteria (1,234 subjects), 7 of which combined hip and knee OA; therefore, we contacted the authors who provided the data on hip OA patients. In comparing exercise treatment versus control, we found a beneficial effect of exercise with an ES of −0.38 (95% confidence interval [95% CI] −0.68, −0.08;P= 0.01), but with high heterogeneity (I2= 75%) among trials. Heterogeneity was caused by 1 trial consisting of an exercise intervention that was not administered in person. Removing this study left 8 trials (n = 493) with similar exercise strategy (specialized hands‐on exercise training, all of which included at least some element of muscle strengthening), and demonstrated exercise benefit with an ES of −0.46 (95% CI −0.64, −0.28;P< 0.0001).ConclusionTherapeutic exercise, especially with an element of strengthening, is an efficacious treatment for hip OA.
Effects of specialized footwear on joint loads in osteoarthritis of the knee
Authors: Shakoor Najia , Lidtke Roy H. , Sengupta Mondira , Fogg Louis F. , Block Joel A. 
Published: August 2008

AbstractObjectiveElevated dynamic joint loads have been associated with the severity and progression of osteoarthritis (OA) of the knee. This study compared the effects of a specialized shoe (the mobility shoe) designed to lower dynamic loads at the knee with self‐chosen conventional walking shoes and with a commercially available walking shoe as a control.MethodsSubjects with knee OA were evaluated in 2 groups. Group A (n = 28) underwent gait analyses with both their self‐chosen walking shoes and the mobility shoes. Group B (n = 20) underwent gait analyses with a control shoe and the mobility shoe. Frontal plane knee loads were compared between the different footwear conditions.ResultsGroup A demonstrated an 8% reduction in the peak external knee adduction moment with the mobility shoe compared with self‐chosen walking shoes (mean ± SD 49 ± 0.80 versus 2.71 ± 0.84 %BW × H; P < 0.05). Group B demonstrated a 12% reduction in the peak external knee adduction moment with the mobility shoe compared with the control shoe (mean ± SD 2.66 ± 0.69 versus 3.07 ± 0.75 %BW × H; P < 0.05).ConclusionSpecialized footwear can effectively reduce joint loads in subjects with knee OA, compared with self‐chosen shoes and control walking shoes. Footwear may represent a therapeutic target for the treatment of knee OA. The types of shoes worn by subjects with knee OA should be evaluated more closely in terms of their effects on the disease.
Features associated with, and the impact of, hemolytic anemia in patients with systemic lupus erythematosus: LX, results from a multiethnic cohort
Authors: Durán Sergio , Apte Mandar , Alarcón Graciela S. , Marion Miranda C. , Edberg Jeffrey C. , Kimberly Robert P. , Zhang Jie , Langefeld Carl D. , ViLá Luis M. , Reveille John D. 
Published: August 2008

AbstractObjectiveTo examine the clinical and genetic correlates of hemolytic anemia and its impact on damage accrual and mortality in systemic lupus erythematosus (SLE) patients.MethodsSLE patients (American College of Rheumatology [ACR] criteria) of Hispanic (Texan or Puerto Rican), African American, and Caucasian ethnicity from the LUMINA (LUpus in MInorities, NAture versus nurture) cohort were studied. Hemolytic anemia was defined as anemia with reticulocytosis (ACR criterion). The association between degrees of hemolytic anemia and socioeconomic/demographic, clinical, pharmacologic, immunologic, psychological, and behavioral variables was examined by univariable and multivariable (proportional odds model) analyses. Genetic variables (FCGR and Fas/Fas ligand polymorphisms) were examined by 2 degrees of freedom test of association and Cochran‐Armitage trend tests. The impact of hemolytic anemia on damage accrual and mortality was examined by multivariable linear and Cox regression analyses, respectively.ResultsOf 628 patients studied, 90% were women, 19% were Texan Hispanic, 16% were Puerto Rican Hispanic, 37% were African American, and 28% were Caucasian. Sixty‐five (10%) patients developed hemolytic anemia at some time during the disease course, 83% at or before diagnosis. Variables independently associated with degrees of hemolytic anemia were African American ethnicity, thrombocytopenia, and the use of azathioprine. Hemolytic anemia was associated with damage accrual after adjusting for variables known to affect this outcome; however, hemolytic anemia was not associated with mortality.ConclusionThe association of hemolytic anemia with thrombocytopenia suggests a common mechanism in their pathophysiology. Hemolytic anemia is an early disease manifestation and is associated with African American ethnicity and the use of azathioprine; it appears to exert an impact on damage but not on mortality.
Implementation of advanced technologies in commercial monoclonal antibody production
Authors: Zhou Joe X. , Tressel Tim , Yang Xiaoming , Seewoester Thomas 
Published: August 2008

AbstractProcess advancements driven through innovations have been key factors that enabled successful commercialization of several human therapeutic antibodies in recent years. The production costs of these molecules are higher in comparison to traditional medicines. In order to lower the development and later manufacturing costs, recent advances in antibody production technologies target higher throughput processes with increased clinical and commercial economics. In this review, essential considerations and trends for commercial process development and optimization are described, followed by the challenges to obtain a high titer cell culture process and its subsequent impact on the purification process. One of these recent technical advances is the development and implementation of a disposable Q membrane adsorber as an alternative to a Q‐packed‐bed column in a flow‐through mode. The scientific concept and principles underlining Q membrane technology and its application are also reviewed.
Application of magnetic force‐based cell patterning for controlling cell–cell interactions in angiogenesis
Authors: Ino Kosuke , Okochi Mina , Honda Hiroyuki 
Published: August 2008

AbstractTo investigate the effects of cell–cell interactions on cellular function, the microenvironment surrounding cells should be precisely controlled. Here, we describe a cell patterning technique, which utilizes magnetic force and magnetite nanoparticles. This method was used to develop cell culture arrays for investigation of cell behaviors in angiogenesis. Pin holder devices that contain more than 6,000 pillars on the surface are used for fabricating the cell culture arrays by setting it on a magnet. The magnetically labeled cells were arranged by magnetic distribution. When the human umbilical vein endothelial cells are arranged at 250 µm intervals (5.9 cells/spot), the cells spread toward other cell cluster on adjacent spots in 4.5 h, and formed cord‐like structures in 8.5 h. It was shown that cell–cell interactions were successfully investigated using magnetic cell arrangement. Biotechnol. Bioeng. 2009; 102: 882–890. © 2008 Wiley Periodicals, Inc.
Dynamic compressive loading influences degradation behavior of PEG‐PLA hydrogels
Authors: Nicodemus G.D. , Shiplet K.A. , Kaltz S.R. , Bryant S.J. 
Published: August 2008

AbstractBiodegradable hydrogels are attractive 3D environments for cell and tissue growth. In cartilage tissue engineering, mechanical stimulation has been shown to be an important regulator in promoting cartilage development. However, the impact of mechanical loading on the gel degradation kinetics has not been studied. In this study, we examined hydrolytically labile gels synthesized from poly(lactic acid)‐b‐poly(ethylene glycol)‐b‐poly‐(lactic acid) dimethacrylate macromers, which have been used for cartilage tissue engineering. The gels were subject to physiological loading conditions in order to examine the effects of loading on hydrogel degradation. Initially, hydrogels were formed with two different cross‐linking densities and subject to a dynamic compressive strain of 15% at 0.3, 1, or 3 Hz. Degradation behavior was assessed by mass loss, equilibrium swelling and compressive modulus as a function of degradation time. From equilibrium swelling, the pseudo‐first‐order reaction rate constants were determined as an indication of degradation kinetics. The application of dynamic loading significantly enhanced the degradation time for the low cross‐linked gels (P < 0.01) while frequency showed no statistical differences in degradation rates or bulk erosion profiles. In the higher cross‐linked gels, a 3 Hz dynamic strain significantly increased the degradation kinetics resulting in an overall faster degradation time by 6 days compared to gels subject to the 0.3 and 1 Hz loads (P < 0.0001). The bioreactor set‐up also influenced overall degradation behavior where the use of impermeable versus permeable platens resulted in significantly lower degradation rate constants for both cross‐linked gels (P < 0.001). The compressive modulus exponentially decreased with degradation time under dynamic loading. Together, our findings indicate that both loading regime and the bioreactor setup influence degradation and should be considered when designing and tuning a biodegradable hydrogel where mechanical stimulation is employed. Biotechnol. Bioeng. 2009; 102: 948–959. © 2008 Wiley Periodicals, Inc.
Flow dynamics in bioreactors containing tissue engineering scaffolds
Authors: Lawrence Benjamin J. , Devarapalli Mamatha , Madihally Sundararajan V. 
Published: August 2008

AbstractBioreactors are widely used in tissue engineering as a way to distribute nutrients within porous materials and provide physical stimulus required by many tissues. However, the fluid dynamics within the large porous structure are not well understood. In this study, we explored the effect of reactor geometry by using rectangular and circular reactors with three different inlet and outlet patterns. Geometries were simulated with and without the porous structure using the computational fluid dynamics software Comsol Multiphysics 3.4 and/or ANSYS CFX 11 respectively. Residence time distribution analysis using a step change of a tracer within the reactor revealed non‐ideal fluid distribution characteristics within the reactors. The Brinkman equation was used to model the permeability characteristics with in the chitosan porous structure. Pore size was varied from 10 to 200 µm and the number of pores per unit area was varied from 15 to 1,500 pores/mm2. Effect of cellular growth and tissue remodeling on flow distribution was also assessed by changing the pore size (85–10 µm) while keeping the number of pores per unit area constant. These results showed significant increase in pressure with reduction in pore size, which could limit the fluid flow and nutrient transport. However, measured pressure drop was marginally higher than the simulation results. Maximum shear stress was similar in both reactors and ranged ∼0.2–0.3 dynes/cm2. The simulations were validated experimentally using both a rectangular and circular bioreactor, constructed in‐house. Porous structures for the experiments were formed using 0.5% chitosan solution freeze‐dried at −80°C, and the pressure drop across the reactor was monitored. Biotechnol. Bioeng. 2009; 102: 935–947. © 2008 Wiley Periodicals, Inc.
Evaluation of metabolism using stoichiometry in fermentative biohydrogen
Authors: Lee Hyung‐Sool , Rittmann Bruce E. 
Published: August 2008

AbstractWe first constructed full stoichiometry, including cell synthesis, for glucose mixed‐acid fermentation at different initial substrate concentrations (0.8–6 g‐glucose/L) and pH conditions (final pH 4.0–8.6), based on experimentally determined electron‐equivalent balances. The fermentative bioH2 reactions had good electron closure (−9.8 to +12.7% for variations in glucose concentration and −3 to +2% for variations in pH), and C, H, and O errors were below 1%. From the stoichiometry, we computed the ATP yield based on known fermentation pathways. Glucose‐variation tests (final pH 4.2–5.1) gave a consistent fermentation pattern of acetate + butyrate + large H2, while pH significantly shifted the catabolic pattern: acetate + butyrate + large H2 at final pH 4.0, acetate + ethanol + modest H2 at final pH 6.8, and acetate + lactate + trivial H2 at final pH 8.6. When lactate or propionate was a dominant soluble end product, the H2 yield was very low, which is in agreement with the theory that reduced ferredoxin (Fdred) formation is required for proton reduction to H2. Also consistent with this hypothesis is that high H2 production correlated with a high ratio of butyrate to acetate. Biomass was not a dominant sink for electron equivalents in H2 formation, but became significant (12%) for the lowest glucose concentration (i.e., the most oligotrophic condition). The fermenting bacteria conserved energy similarly at ∼3 mol ATP/mol glucose (except 0.8 g‐glucose/L, which had ∼3.5 mol ATP/mol glucose) over a wide range of H2 production. The observed biomass yield did not correlate with ATP conservation; low observed biomass yields probably were caused by accelerated rates of decay or production of soluble microbial products. Biotechnol. Bioeng. 2009; 102: 749–758. © 2008 Wiley Periodicals, Inc.
Generation of New Derivatives of the Antitumor Antibiotic Mithramycin by Altering the Glycosylation Pattern through Combinatorial Biosynthesis
Authors: Pérez María , Baig Irfan , Braña Alfredo F. , Salas José A. , Rohr Jürgen , Méndez Carmen 
Published: August 2008

AbstractMithramycin is an antitumor drug produced by Streptomyces argillaceus. It consists of a tricyclic aglycone and five deoxyhexoses that form a disaccharide and a trisaccharide chain, which are important for target interaction and therefore for the antitumor activity. Using a combinatorial biosynthesis approach, we have generated nine mithramycin derivatives, seven of which are new compounds, with alterations in the glycosylation pattern. The wild‐type S. argillaceus strain and the mutant S. argillaceus M7U1, which has altered D‐oliose biosynthesis, were used as hosts to express various “sugar plasmids”, each one directing the biosynthesis of a different deoxyhexose. The newly formed compounds were purified and characterized by MS and NMR. Compared to mithramycin, they contained different sugar substitutions in the second (D‐olivose, D‐mycarose, or D‐boivinose instead of D‐oliose) and third (D‐digitoxose instead of D‐mycarose) sugar units of the trisaccharide as well as in the first (D‐amicetose instead of D‐olivose) sugar unit of the disaccharide. All compounds showed antitumor activity against different tumor cell lines. Structure–activity relationships are discussed on the basis of the number and type of deoxyhexoses present in these mithramycin derivatives.
Site‐Specific Chemical Modification of Proteins with a Prelabelled Cysteine Tag Using the Artificially Split Mxe GyrA Intein
Authors: Kurpiers Thomas , Mootz Henning D. 
Published: August 2008

AbstractThe selective modification of proteins with a synthetic probe is of central interest for many aspects of protein chemistry. We have recently reported a new approach in which a short cysteine‐containing tag (CysTag) fused to one part of a split intein is first modified with a sulfhydryl‐reactive probe. In a second step, protein trans‐splicing is used to link the labelled CysTag to a target protein that has been expressed in fusion with the complementary split intein fragment. Here, we present the generation and biochemical characterisation of the artificially split Mycobacterium xenopi GyrA intein. We show that this split intein is active without a renaturation step and that it provides a significant improvement for the CysTag protein‐labelling approach in terms of product yields and target protein tolerance. Two proteins with multiple cysteine residues, human growth hormone and a multidomain nonribosomal peptide synthetase, were site‐specifically modified with high yields. Our approach combines the benefits of the plethora of commercially available cysteine‐reactive probes with a straightforward route for their site‐specific incorporation even into complex and cysteine‐rich proteins.
Comparison of Design Strategies for Promotion of β‐Peptide 14‐Helix Stability in Water
Authors: Vaz Esther , Pomerantz William C. , Geyer Matthias , Gellman Samuel H. , Brunsveld Luc 
Published: August 2008

AbstractMany short β‐peptides adopt well‐defined conformations in organic solvents, but specialized stabilizing elements are required for folding to occur in aqueous solution. Several different strategies to stabilize the 14‐helical secondary structure in water have been developed, and here we provide a direct comparison of three such strategies. We have synthesized and characterized β‐peptide heptamers in which variously a salt bridge between side chains, a covalent link between side chains, or two cyclically constrained residues have been incorporated to promote 14‐helicity. The incorporation of a salt bridge does not generate significant 14‐helicity in water, according to CD and 2D NMR data. In contrast, incorporation either of a lactam bridge between side chains or of cyclic residues results in stable 14‐helices in water. The β‐peptides featuring trans‐2‐aminocyclohexanecarboxylic acid (ACHC) residues show the highest 14‐helical backbone stability, with hardly any sensitivity to pH or ionic strength. The β‐peptides featuring side‐chain‐to‐side‐chain cyclization show lower 14‐helical backbone stability and higher sensitivity to pH and ionic strength, but increased order between the side chains because of the cyclization.
Small‐Molecule Negative Modulators of Adrenomedullin: Design, Synthesis, and 3D‐QSAR Study
Authors: Roldós Virginia , Martín‐Santamaría Sonsoles , Julián Miguel , Martínez Alfredo , Choulier Laurence , Altschuh Danièle , de Pascual‐Teresa Beatriz , Ramos Ana 
Published: August 2008

AbstractAdrenomedullin (AM) is a peptidic hormone that was isolated in 1993, the function of which is related to several diseases such as diabetes, hypertension, and cancer. Compound 1 is one of the first nonpeptidic small‐molecule negative modulators of AM, identified in a high‐throughput screen carried out at the National Cancer Institute. Herein we report the synthesis of a series of analogues of 1. The ability of the synthesized compounds to disrupt the binding between AM and its monoclonal antibody has been measured, together with surface plasmon resonance (SPR)‐based binding assays as implemented with Biacore technology. These data were used to derive a three‐dimensional quantitative structure–activity relationship (3D‐QSAR) model, with a q2 (LOO) value of 0.8240. This study has allowed us to identify relevant features for effective binding to AM: the presence of a hydrogen‐bond donor group and an aromatic ring. Evaluation of the ability of selected compounds to modify cAMP production in Rat2 cells showed that the presence of a free carboxylic acid is essential for negative AM modulation.
Apoptosis‐Inducing High .NO Concentrations Are Not Sustained Either in Nascent or in Developed Cancers
Authors: Heller Adam 
Published: August 2008

AbstractNitric oxide (.NO) induces apoptosis at high concentrations by S‐nitrosating proteins such as glyceraldehyde‐3‐phosphate dehydrogenase. This literature analysis revealed that failure to sustain high .NO concentrations is common to all cancers. In cervical, gastric, colorectal, breast, and lung cancer, the cause of this failure is the inadequate expression of inducible nitric oxide synthase (iNOS), resulting from the inhibition of iNOS expression by TGF‐β1 at the mRNA level. In bladder, renal, and prostate cancer, the reason for the insufficient .NO levels is the depletion of arginine, resulting from arginase overexpression. Arginase competes with iNOS for arginine, catalyzing its hydrolysis to ornithine and urea. In gliomas and ovarian sarcomas, low .NO levels are caused by inhibition of iNOS by N‐chlorotaurine, produced by infiltrating neutrophils. Stimulated neutrophils express myeloperoxidase, catalyzing H2O2 oxidation of Cl− to HOCl, which N‐chlorinates taurine at its concentration of 19 mM in neutrophils. In squamous cell carcinomas of the skin, ovarian cancers, lymphomas, Hodgkin's disease, and breast cancers, low .NO concentrations arise from the inhibition of iNOS by N‐bromotaurine, produced by eosinophil‐peroxidase‐expressing infiltrating eosinophils. Eosinophil peroxidase catalyzes the H2O2 oxidation of Br− to HOBr, which N‐brominates taurine to N‐bromotaurine at its concentration of 15 mM in eosinophils. In microvascularized tumors, the .NO concentration is further depleted; .NO is rapidly consumed by red blood cells (RBCs) through S‐nitrosation of RBC glutathione and hemoglobin, and by oxidation to nitrate by RBC oxyhemoglobin. Angiogenesis‐inhibiting antibodies are currently used to treat cancers; their mode of action is not, as previously thought, reduction of the tumor O2 or nutrient supply. They actually decrease the loss of .NO to RBCs.