bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights into the pathogenesis of Paget's disease
Authors: Roodman G. David
Published: April 2010

Paget's disease (PD) affects approximately 1.5 million persons in the United States and is characterized by grossly distorted bone remodeling, with increases in bone resorption and formation. Both environmental and genetic factors may contribute to the pathogenesis of PD. Mutations in sequestosome‐1 (p62) occur in 25–30% of patients with familial PD, and in ∼10% of patients with sporadic PD. Preclinical studies suggest that the p62P392L mutation predisposes patients to developing PD rather than causing it. Other studies have suggested that PD results from a chronic paramyxoviral infection. Transgenic mice expressing the measles virus nucleocapsid gene (MVNP) in osteoclasts (OCLs) develop pagetic bone lesions. Further, approximately 70% of patients harboring the p62P392L mutation we studied have detectable MVNP transcripts, and inhibiting MVNP expression in bone marrow cultures from those patients blocked pagetic OCL formation. These studies suggest that both genetic and environmental factors contribute to PD.
Purification and identification of estrogen receptor alpha co‐regulators in osteoclasts
Authors: Takada Ichiro , Tsuji Naoya , Youn Min‐Young , Fujiyama Sally , Okada Maiko , Imai Yuuki , Kondo Shino , Kitakawa Hirochika , Yasuda Hisataka , Kato Shigeaki
Published: April 2010

Mature osteoclasts are multinuclear, macrophage‐like cells derived from hematopoietic stem cells in the bone marrow. Several transcription factors regulating osteoclast differentiation have been identified. However, the molecular basis of transcriptional regulation in osteoclasts at epigenetic levels is largely unknown. In fact, no osteoclast‐specific transcriptional co‐regulators have been characterized. Recently, selective ablation of estrogen receptor alpha (ERα) in mature osteoclasts derived from female mice (ERαΔoc/Δoc) exhibited trabecular bone loss due to induced apoptosis via upregulated expression of Fas ligand mRNA. In general, the component composition of the ERα‐associated co‐activator complex and its expression levels are distinct among tissues. However, ERα transcriptional co‐regulators in mature osteoclasts remain unclear. In the present study, we achieved large‐scale cultivation of mature, multinucleated osteoclasts and established a purification system for ERα‐associated proteins. In addition to co‐regulators previously found in other ERα target cells, several unexpected factors were found such as CAP‐H. The mRNA expression level of CAP‐H was high during osteoclast differentiation. These results demonstrate the existence of osteoclast‐specific transcriptional co‐regulators supporting ERα function.
PLCγ2: where bone and immune cells find their common ground
Authors: Faccio Roberta , Cremasco Viviana
Published: April 2010

Identifying common signaling pathways to bone and immune system may lead to better therapeutic approaches in diseases such as inflammatory arthritis. In this context, PLCγ2 seems to be a promising target. PLCγ2 modulates bone homeostasis by affecting osteoclast recruitment and function. Via its catalytic activity and the adapter domains, PLCγ2 controls RANKL and αvβ3 integrin‐dependent signaling pathways in the resorbing cell. Thus, mice lacking PLCγ2 are osteopetrotic. PLCγ2 also regulates neutrophil degranulation after β2 integrin‐dependent attachment. Indeed PLCγ2−/− mice are protected from K/BxN serum transfer arthritis, which is known to require neutrophil activation. These studies position PLCγ2 as a critical regulator of the cellular and molecular mechanisms occurring in bone and immune cells during autoimmune inflammation.
The HSC niche concept has turned 31
Authors: Lymperi Stefania , Ferraro Francesca , Scadden David T.
Published: April 2010

The hematopoietic stem cell (HSC) niche is currently defined as the specific microenvironment in the bone marrow (BM) which anatomically harbors HSCs and governs their fate. It plays a pivotal role in regulating the survival and self‐renewal ability of HSCs, protecting them from exhaustion while preventing their excessive proliferation. Many different stromal cell types have been proposed as putative constituents of the niche, but their integrated function is still unrevealed. Mechanisms by which stem/progenitor cell behavior is regulated in the niche include cell‐to‐cell interaction and the production of growth factors, cytokines, and extracellular matrix proteins. The HSC niche is a dynamic entity reflecting and responding to the needs of the organism. An understanding of how the niche participates in the maintenance of tissue homeostasis and repair offers new opportunities for the development of novel therapeutic tools.
Congenital adrenal hyperplasia due to 21‐hydroxylase deficiency
Authors: Nimkarn Saroj , New Maria I.
Published: April 2010

21‐Hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia (CAH), an inherited disorder of steroidogenesis. In its severe form, CAH causes genital ambiguity in females. Molecular genetic analysis of fetal DNA obtained by amniocentesis or chorionic villus sampling is used to diagnose steroid 21‐OHD deficiency in utero. Large ongoing studies show that appropriate prenatal treatment of pregnant mothers with dexamethasone is effective and safe for both the fetus and the mother. It reduces ambiguous genitalia in the female affected fetus and thus avoids unnecessary genitoplasty in the newborn female.
Vitamin D action
Authors: Goltzman David
Published: April 2010

Mouse models with targeted deletion of the genes encoding the enzyme 25‐hydroxyvitamin D 1alpha‐hydroxylase [1α(OH)ase], and the vitamin D receptor (VDR), have provided considerable insight into the regulation of mineral and skeletal physiology by 1,25‐dihydroxyvitamin D [1,25(OH)2D]. Dietary manipulation induced different phenotypic changes and demonstrated that parathyroid gland function is coordinately regulated by calcium and 1,25(OH)2D, but that mineralization of bone reflects ambient calcium (and phosphorus) levels rather than direct actions of the 1,25(OH)2D/VDR system. In contrast, increased calcium absorption and optimal osteoblastogenesis and bone formation is modulated by the 1,25(OH)2D/VDR system. Similar models have also been employed to study extraskeletal vitamin D actions. For example, increased blood pressure, activation of the renin/angiotensin system, myocardial hypertrophy, and cardiac dysfunction were observed in 1αOHase−/− mice, and could be prevented by 1,25(OH)2D3 administration. These models allow controlled examination of the pathophysiology associated with1,25(OH)2D deficiency and intervention to prevent and treat these disorders.
Glucocorticoid‐induced bone fragility
Authors: Lane Nancy E. , Yao Wei
Published: April 2010

Glucocorticoid (GC) use results in rapid bone loss and an elevated risk of fracture. The excess bone fragility from GC treatment is multifactorial. GCs increase bone remodeling through reductions in gonadal hormones, elevations in PTH from negative calcium balance, early stimulation of osteoclast maturation and activity, and delayed, sustained reduction in osteogenesis and osteoblast activity. GCs also alter the metabolism of osteocytes so that increased osteocyte lacunae size, with demineralization around the osteocyte and reduced elastic modulus, is observed in a mouse model of GC‐induced bone loss. In summary, GC effects on bone fragility are multifactorial, and additional studies are now under way to clarify how GCs alter osteocyte metabolism and result in reduction in localized bone strength.
ACTH is a novel regulator of bone mass
Authors: Isales Carlos M. , Zaidi Mone , Blair Harry C.
Published: April 2010

Adrenocorticotropin (ACTH) is one of several peptide hormones derived from a larger molecule, proopiomelanocortin (POMC). ACTH is a classic endocrine hormone, processed and secreted from the pituitary to stimulate cortisol production from the fasciculata cells in the adrenal gland. However, ACTH is also produced by other cells, including macrophages, at many sites in the body. ACTH binds to a specific member of the melanocortin receptor family, the MC2R. MC2R is expressed in osteoblastic cells in vivo, as shown by in situ hybridization. MC2R expression is strongest at sites of active bone deposition, and thus ACTH response probably varies with osteoblastic activity or stage of osteoblast differentiation. In vitro ACTH stimulates proliferation of osteoblasts in a dose‐dependent manner. ACTH at 10 nM increases collagen I mRNA in the osteoblastic cell line SaOs2, although at lower concentrations ACTH may oppose osteoblast differentiation. ACTH is thus, at high concentrations, anabolic for the osteoblast, and it is highly likely that the hormone has concentration‐dependent effects on bone metabolism in vivo.
How does human bone resist fracture?
Authors: Ritchie Robert O.
Published: April 2010

The fracture of bone is clearly a major health concern, especially for the elderly. Medical therapies to reduce the possibility of bone fracture to date have principally centered on treating the loss in bone mass (bone mineral density) that accompanies aging (i.e., addressing the loss in bone quantity). However, it is now known that there is an additional, perhaps more significant, effect of the degradation in the inherent properties of bone (i.e., a loss in bone quality) with age. To address this issue, we review here the structure and properties of bone, focusing on its strength and fracture resistance from the perspective of the multidimensional hierarchical nature of its structure. We show that bone derives its resistance to fracture from a multitude of deformation and toughening mechanisms at many of these size‐scales, ranging from the nanoscale structure of its protein molecules to its macroscopic physiological state.
Role of HIF‐1α in skeletal development
Authors: Wan Chao , Shao Jin , Gilbert Shawn R. , Riddle Ryan C. , Long Fanxin , Johnson Randall S. , Schipani Ernestina , Clemens Thomas L.
Published: April 2010

Angiogenesis and osteogenesis are tightly coupled during bone development and regeneration. Mesenchymal cells in the developing stroma elicit angiogenic signals to recruit new blood vessels into bone. Reciprocal signals, likely emanating from the incoming vascular endothelium, stimulate mesenchymal cell specification through additional interactions with cells within the vascular stem cell niche. The hypoxia‐inducible factor‐1 alpha (HIF‐1) pathway has been identified as a key component in this process. We demonstrated that overexpression of HIF‐1 in mature osteoblasts through disruption of the von Hippel‐Lindau protein profoundly increases angiogenesis and osteogenesis; these processes appear to be coupled by cell nonautonomous mechanisms involving the action of vascular endothelial growth factor (VEGF) on the endothelial cells. The same occurred in the model of injury‐mediated bone regeneration (distraction osteogenesis). Surprisingly, manipulation of HIF‐1 does not influence angiogenesis of the skull bones, where earlier activation of HIF‐1 in the condensing mesenchyme upregulates osterix during cranial bone formation.
Role of the polycytin‐primary cilia complex in bone development and mechanosensing
Authors: Xiao Z.S. , Quarles L.D.
Published: April 2010

Pkd1 encodes PC1, a transmembrane receptor‐like protein, and Pkd2 encodes PC2, a calcium channel, which interact to form functional polycystin complexes that are widely expressed in many tissues and cell types. The study of autosomal dominant polycystic kidney disease (ADPKD), caused by inactivating mutations of PKD1 or PKD2 genes, has elucidated the functions of polycystins and their interdependence on primary cilia in renal epithelial cells. We have found that Pkd1 and Pkd2, as well as primary cilia, are present in osteoblasts and osteocytes. In addition, we have found that loss of polycystin‐1 (Pkd1) function in mice results in abnormal bone development and osteopenia due to the impaired differentiation of osteoblasts. It is likely that the polycytin/primary cilia complex responds to a multitude of environmental clues affecting skeletal development and bone formation postnatally. Overall, polycystins in bone may define a new target for developing anabolic agents to treat osteoporotic disorders.
Calmodulin—an often‐ignored signal in osteoclasts
Authors: Williams John P. , Micoli Keith , McDonald Jay M.
Published: April 2010

Calcium signaling plays a key role in bone turnover, regulating both osteoblasts and osteoclasts. Despite this the role of calmodulin, the primary intracellular calcium receptor regulatory protein, has received little attention. In this brief review, the function of Ca2+/calmodulin signaling in osteoclast development, function, and apoptosis is reviewed. Considerable evidence supports an important regulatory role for Ca2+/calmodulin signaling in each of these processes. The overall role of Ca2+/calmodulin in regulating bone turnover is also supported by animal and human studies showing that calmodulin antagonists preserve bone mass.
Osteocyte primary cilium and its role in bone mechanotransduction
Authors: Temiyasathit Sara , Jacobs Christopher R.
Published: April 2010

Bone is a dynamic tissue that adapts to its local loading environment. Mechanotransduction, the process by which cells convert mechanical forces into biochemical signals, is important for maintaining bone health and homeostasis. It is less clear, however, what the cellular mechanosensor(s) are that sense and initiate these signaling cascades. Primary cilia are solitary rigid structures that extend from the cell body into the extracellular space and as a consequence are prime candidates for mechanosensing in bone. Primary cilia have been shown to be critical in development and have been implicated in mechanosensing in other tissue types, including liver and kidney. In this review we discuss the potential for primary cilia to play an important role in bone mechanotransduction and possible avenues for future study.
Nuclear factor‐κB p50 subunits in chronic periodontitis and Porphyromonas gingivalis lipopolysaccharide‐pulsed dendritic cells
Authors: Jotwani Ravi , Moonga Baljit S. , Gupta Siddharth , Cutler Christopher W.
Published: April 2010

The pathogenesis of a number of chronic inflammatory diseases has been linked to dysregulated functioning of nuclear transcription factor (NF)‐κB. In the present study, we examine NF‐κB activation in human oral mucosal tissues of chronic periodontitis (CP) patients. Electrophoretic mobility shift assay and DNA‐binding enzyme‐linked immunosorbent assays indicate elevated levels of transcriptionally repressive p50 subunits and an increased p50/p65 ratio in CP tissues compared to healthy controls. Because Porphyromonas gingivalis has been recognized to be a causal factor in CP, we used P. gingivalis lipopolysaccharide (LPS) for in vitro studies with monocyte‐derived dendritic cells (MoDCs). Porphyromonas gingivalis LPS, unlike Escherichia coli LPS, induced an increased p50/p65 ratio in MoDCs. Using blocking antibodies, we demonstrated that while both Toll‐like receptor 2 (TLR2) and TLR4 are required for MoDC maturation by P. gingivalis LPS, only TLR4 signaling is sufficient to induce cytokine secretion. Our results suggest that increased levels of transcriptionally repressive p50 may be characteristic of CP and might be a result of suboptimal NF‐κB activation and dendritic cell maturation by P. gingivalis, a bacterium implicated in CP.
New immune connections in osteoclast formation
Authors: Takayanagi Hiroshi
Published: April 2010

Osteoimmunology is an interdisciplinary research field that investigates the interplay of the skeletal and immune systems at the molecular level. The interaction between immune cells and osteoclasts has been a major topic in this field. As osteoclasts are derived from the monocyte/macrophage lineage, the macrophage–osteoclast interaction has long been studied. The T cell–osteoclast interaction has also attracted much attention in the study of bone destruction in arthritis. In addition, recent reports have revealed new players linking osteoclasts and other immune cells, including B cells and dendritic cells. Thus, a large number of molecules are in fact shared by osteoclasts and immune cells. These findings will lead to a better understanding of the pathogenesis of diseases affecting both systems and will provide a molecular basis for novel therapeutic strategies.
Functions of nuclear factor κB in bone
Authors: Boyce Brendan F. , Yao Zhenqiang , Xing Lianping
Published: April 2010

Nuclear factor κB (NF‐κB) is a set of multifunctional transcription factors that regulate expression of genes involved in numerous normal cellular activities. They also are activated in many inflammatory and neoplastic conditions in which their expression may be stimulated by proinflammatory cytokines. NF‐κB, in turn, regulates the expression of cytokines and so can mediate autocrine self‐amplifying cycles of cytokine release and NF‐κB activation, leading to maintenance of inflammatory reactions beyond the initial stimulus, as seen in rheumatoid arthritis and asthma. Since discovery of the requirement of NF‐κB for basal and cytokine‐induced osteoclast formation in the mid‐1990s, much has been learned about the role of NF‐κB in bone. NF‐κB has roles in skeletal development, endochondral ossification, osteoclast and osteoblast functions, and common bone diseases. NF‐κB inhibitors have been developed, but none have made it to clinical trials for the treatment of common bone diseases. Here we review the roles for NF‐κB in bone and in common bone diseases.
Zinc finger protein 521, a new player in bone formation
Authors: Hesse Eric , Kiviranta Riku , Wu Meilin , Saito Hiroaki , Yamana Kei , Correa Diego , Atfi Azeddine , Baron Roland
Published: April 2010

Exploration of anabolic pathways in osteoblasts revealed that Zfp521, a 30‐zinc finger protein, is highly expressed at the periphery of mesenchymal condensations and in developing bones. In these structures it is expressed in chondroblasts, prehypertrophic chondrocytes, the periosteum, osteoblasts, osteoblast precursors, and osteocytes. Forced expression of Zfp521 in osteoblasts in vivo increases bone formation and bone mass, whereas preliminary data suggest that germline deletion leads to osteopenia. In contrast, overexpressing Zfp521 in vitro antagonizes, and knockdown favors, osteoblast differentiation and nodule formation. Zfp521 expression is inhibited by bone morphogenetic protein‐2 and stimulated by parathyroid hormone‐related protein. Mechanistically, Zfp521 binds to Runx2, repressing its transcriptional activity. These data support the hypothesis that Zfp521 both opposes the progression of precursors and promotes the maturation and function of mature osteoblasts. The balance between Zfp521 and Runx2 may therefore contribute to the regulation of osteoblast differentiation and bone formation.
Complexity in signal transduction
Authors: Iqbal Jameel , Sun Li , Zaidi Mone
Published: April 2010

This review is focused on complexity in cell signaling. Signaling experiments have demonstrated that many different stimuli activate the same signaling pathways yet result in different outcomes. Differences in the cellular machinery between cells explain response variation between cell types, but for a single cell type an appealing explanation is still lacking. The kinetic disconnect between cell signal transduction and a cellular action is highlighted; possible explanations for this disconnect, such as a series of cascading autocrine signaling molecules and new research suggesting that cells experience multiple rounds of reactivation in numerous cell signaling pathways, are reviewed. Additionally, evidence that kinase pathways exhibit frequency and amplitude modulation is examined. From this review, a new model of signal transduction is proposed whereby multiple signal transduction pathways are reactivated over time to orchestrate unique outcomes in physiological processes.
Suicide Terrorism
Authors: Weinberg Leonard , Pedahzur Ami
Published: April 2010

Suicide bombing has become the most potent weapon in the arsenal of terrorist groups in the Middle East, South Asia, and elsewhere. This analysis traces the weapon’s history, both ancient and modern to the present day. It includes commentary on the benefits and costs of suicide attacks as well as the motives of the ‘martyrs’ themselves and the organizations that send them on their way. Finally, the analysis pays attention to countermeasures, policies at the disposal of the authorities to stop or at least inhibit so‐called ‘martyrdom operations.’
Advancing Religious Pluralism in Islam
Authors: Sachedina Abdulaziz
Published: April 2010

Pluralism in the context of religion suggests both diversity of interpretation of the foundational sources of that tradition and relativity implied in such plurality of hermeneutics. At this time, a number of Muslim scholars writing from traditional centers of Islamic learning in the Middle East are resisting the implications of pluralistic discourse on religion. There is a deep‐seated fear of secularly inspired relativism about religious truth that, according to these scholars, belief in pluralism might destabilize the authority of revelation as well as the tradition that has determined the authenticity of its foundational sources and the praxis for the faith community. It is important to bear in mind that this traditional defensive discourse against pluralism has nothing to do with the recognition of peaceful interfaith relations as the cornerstone of contemporary pluralistic political and social order. In fact, the growing interest in minority jurisprudence (fiqh ) in a number of traditional centers indicates the acknowledgement, though not whole‐hearted acceptance, of the reality of the modern world in which plurality of religious traditions has been recognized as a major principle of co‐existence. However, this does not necessarily mean that pluralism has been acknowledged as an epistemic source of critical reassessment of Islamic theological and metaphysical notions for a new inclusive political theology.
Fungal Inactivation by Mexican Oregano (Lippia berlandieri Schauer) Essential Oil Added to Amaranth, Chitosan, or Starch Edible Films
Authors: Avila‐Sosa Raúl , Hernández‐Zamoran Erika , López‐Mendoza Ingrid , Palou Enrique , Munguía María Teresa Jiménez , Nevárez‐Moorillón Guadalupe Virginia , López‐Malo Aurelio
Published: April 2010

ABSTRACT:  Edible films can incorporate antimicrobial agents to provide microbiological stability, since they can be used as carriers of a wide number of additives that can extend product shelf life and reduce the risk of pathogenic bacteria growth on food surfaces. Addition of antimicrobial agents to edible films offers advantages such as the use of low antimicrobial concentrations and low diffusion rates. The aim of this study was to evaluate inhibition of Aspergillus niger and Penicillium spp. by selected concentrations of Mexican oregano (Lippia berlandieri Schauer) essential oil added to amaranth, chitosan, or starch edible films. Oregano essential oil was characterized by gas chromatography‐mass spectrometry (GC/MS) analysis. Amaranth, chitosan, and starch edible films were formulated with essential oil concentrations of 0%, 0.25%, 0.50%, 0.75%, 1%, 2%, and 4%. Mold radial growth was evaluated inoculating spores in 2 ways: edible films were placed over inoculated agar, Film/Inoculum mode (F/I), or the edible films were first placed in the agar and then films were inoculated, Inoculum/Film mode (I/F). The modified Gompertz model adequately described growth curves. There was no significant difference (P > 0.05) in growth parameters between the 2 modes of inoculation. Antifungal effectiveness of edible films was starch > chitosan > amaranth. In starch edible films, both studied molds were inhibited with 0.50% of essential oil. Edible films added with Mexican oregano essential oil could improve the quality of foods by controlling surface growth of molds.
Impact of Harvesting and Processing Conditions on Green Leaf Volatile Development and Phenolics in Concord Grape Juice
Authors: Iyer M.M. , Sacks G.L. , Padilla‐Zakour O.I.
Published: April 2010

ABSTRACT:  The disruption of plant cell walls during fruit juice processing results in the enzymatic formation of herbaceous‐smelling green leaf volatiles (GLVs). Our objective was to assess the impact of thermal processing conditions on resulting levels of GLVs (hexanal, trans‐2‐hexenal, hexanol, cis‐3‐hexenol, and trans‐2‐hexenol), total phenols, monomeric anthocyanins, and percent polymeric color in Concord grape juice. The effects of fruit maturity and stage of juice processing on juice GLV content was also assessed. Of the GLVs studied, only trans‐2‐hexenal routinely exceeded its published sensory threshold in finished juice. We observed an inverse linear correlation between berry maturity (total soluble solids) and trans‐2‐hexenal levels in finished juice (P < 0.05, R 2= 0.91). Trans‐2‐hexenal was at a maximum immediately following crushing (569 μg/kg, >30‐fold over detection threshold [DT]), decreased to 100 μg/kg following depectinization, pressing, and pasteurization, and to 32 μg/kg following cold‐stabilization. The loss of trans‐2‐hexenal could be explained primarily by its reduction to trans‐2‐hexenol, which increased from 53 μg/kg after crushing to 500 μg/kg after cold‐stabilization. High temperature pretreatment of must immediately following crushing (“hot break”) resulted in 5‐ to 6‐fold higher concentrations of trans‐2‐hexenal in the final bottled juice as compared to conventional hot press. Contrary to expectations, no significant increase in phenolics and anthocyanins were observed in hot break conditions. These results indicate that hot break procedures may thermally inactivate enzymes responsible for transforming trans‐2‐hexenal under normal processing conditions and potentially alter the flavor qualities of the finished Concord juice. Different equivalent pasteurization regimes (82 to 93 °C) prior to bottling had no significant effect on GLV content of the finished Concord juices (P > 0.05).

Practical Application: Introducing new processing techniques to fruit juice production can potentially result in undesirable changes to organoleptic properties. We have observed significantly higher levels of trans‐2‐hexenal, a potent herbaceous off‐flavor, in Concord grape juice prepared with an initial high temperature heat treatment (“hot break”). Concord juice producers should be cautious in using hot break processing, especially with immature fruit, as it may result in persistence of green aromas in juice.
Retention of Antioxidant Capacity of Vacuum Microwave Dried Cranberry
Authors: Leusink Gwen J. , Kitts David D. , Yaghmaee Parastoo , Durance Tim
Published: April 2010

ABSTRACT: In this study, cranberries were dried by vacuum‐microwave drying (VMD), freeze‐drying (FD), or hot air‐drying (AD), to compare the effects of different drying processes on both physical changes as well as the retention of bioactive components in dried samples. Total porosity (%) and average pore radius of dehydrated cranberries were greater using VMD compared to FD and AD (P < 0.05). Crude methanol cranberry powdered extracts were fractionated by solid phase extraction (SPE) into organic acid‐, total phenolics‐, anthocyanin‐, or proanthocyanidin‐enriched extracts, respectively. The chemical composition of the 60% acidified methanol fractions contained cyanidin‐3‐galactoside, cyanidin‐3‐arabinoside, peonidin‐3‐galactoside, and peonidin‐3‐arabinoside, as assessed by HPLC. Antioxidant activities of cranberry fractions were measured using chemical ORAC and ABTS methods. The 60% acidified methanol fraction had a significantly higher (P < 0.05) antioxidant potential than the other chemical fractions, which was largely attributed to the relatively higher anthocyanin content. In general, vacuum‐microwave drying and freeze‐drying resulted in similar retention of anthocyanins and antioxidant activity, which were both relatively higher (P < 0.05) than that recovered from cranberries dried by hot air drying.
The 6‐Minute Walk Is Associated With Frailty and Predicts Mortality in Older Adults With Heart Failure
Authors: Boxer Rebecca , Kleppinger Alison , Ahmad Amir , Annis Kristin , Hager David , Kenny Anne
Published: April 2010

Heart failure (HF) may contribute to the development of functional decline and frailty in older adults. Sixty HF patients with an ejection fraction ≤40% evaluated in 2004 and 2005 were reevaluated in 2008. Six‐minute walk distance (6MW), frailty score, and biomarkers (25‐hydroxyvitamin D, C‐reactive protein, and interleukin‐6 [IL‐6]) were measured. Participants were categorized at baseline and follow‐up into 3 groups: nonfrail/normal endurance (NF/NE), nonfrail/low endurance (NF/LE) and frail/low endurance (F/LE). Survival time was assessed according to frailty/endurance status and associated predictors of mortality. Forty‐three men, 17 women (mean age, 78±12 years) were contacted. At follow‐up, 20 had died, 20 participated, and 20 did not participate. There were no changes in frailty/endurance status over time (McNemar;P=.19). Deaths occurred in 18% of NF/NE, 45% of NF/LE, and 60% of F/LE persons. The NF/NE group had greater survival rates than the NF/LE (  P=.032) and F/LE (  P=.014) groups. The 6MW and frailty score were independently predictive of mortality, with hazard ratios of 0.82 (95% confidence interval, 0.72–0.94) and 1.64 (95% confidence interval, 1.19–2.26), respectively, as was New York Heart Association class and IL‐6. Backward stepwise Cox regression revealed that 6MW and frailty each were associated with mortality (P=.005) and highly correlated. Physical function is an important predictor of mortality in older adults with HF. The 6MW may be useful as a measure of frailty. Congest Heart Fail. 2010;16:208–213. © 2010 Wiley Periodicals, Inc.
Assessing Competencies in Couples and Family Therapy/Counseling: A Call to the Profession
Authors: Perosa Linda M. , Perosa Sandra L.
Published: April 2010

Psychometrically sound measures of family therapy competencies are necessary to assess the effectiveness of training on student performance. This article critiques the self‐report and observer rating measures developed to date to assess the clinical skills of trainees in the individual and in the family therapy fields. Suggestions are made to foster future instrument development specifically designed for the field of couples and family therapy/counseling.
Optimal cut‐off point of waist circumference for the diagnosis of metabolic syndrome in Japanese subjects
Authors: Ogawa Daisuke , Kahara Kenji , Shigematsu Terunobu , Fujii Soichiro , Hayakawa Nobuhiko , Okazaki Morihiro , Makino Hirofumi
Published: April 2010

Metabolic syndrome (MetS) has been redefined by a new criterion in Japan, in which waist circumference cut‐off points, that is 85 cm for men and 90 cm for women, are used; however, objections are rising against this criterion. The present study examined the criterion for waist circumference to predict the accumulation of the components of MetS. In the present study, we used data for 5972 Japanese people who received annual health examinations, and 621 men (16.3%) and 51 women (2.4%) were diagnosed as having MetS. A cut‐off point as a predictor for two or more components of MetS was evaluated by the sensitivity/specificity and a receiver operating characteristic analysis. The optimal point of waist circumference was estimated as being approximately 84 cm for men and 80 cm for women. We therefore recommend revising the cut‐off value for the criterion of MetS in women according to our results and studies from other investigators. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00020.x, 2010)
Effect of the combination of mitiglinide and metformin on glycemic control in patients with type 2 diabetes mellitus
Authors: Cho Young Min , Koo Bo Kyung , Son Ho Young , Lee Kwang Woo , Son Hyun Shik , Choi Dong Seop , Kim Bo Wan , Kim Yong Ki , Lee Moon Kyu , Lee Hyun Chul , Min Kyung Wan , Chung Min Young , Baek Hong Sun , Kim Youngkun , Yoo Hyung Joon , Park Kyong Soo , Lee Hong Kyu
Published: April 2010

Aims/Introduction: Mitiglinide is the newest drug in the meglitinide family. It increases the early‐phase insulin release through rapid association‐dissociation kinetics in the pancreatic β cells. The efficacy and safety of adding meglitinide to metformin monotherapy in patients with type 2 diabetes are unknown.

Materials and Methods: We carried out a prospective, randomized, multicenter trial to assess the efficacy and safety of combined treatment with mitiglinide and metformin for patients with type 2 diabetes who showed inadequate glycemic control with metformin monotherapy. Subjects with glycated hemoglobin (HbA1c) >7.0% after an 8‐week metformin run‐in phase were randomized to a 16‐week trial phase with metformin plus mitiglinide (Met + Mit) or metformin plus placebo (Met + Pcb).

Results: Compared with the Met + Pcb group, the Met + Mit group showed a greater reduction in HbA1c(−0.7 ± 0.6%vs−0.4 ± 0.7%,P = 0.002), fasting plasma glucose (−0.77 ± 1.76 mmol/Lvs−0.05 ± 1.60 mmol/L,P = 0.015) and 2‐h postprandial glucose (−3.76 ± 3.57 mmol/Lvs−0.84 ± 3.07 mmol/L,P < 0.0001). The proportion of the patients who achieved the target HbA1cvalue of <7% at the end of the study was also higher in the Met + Mit group than the Met + Pcb group (49.3%vs28.8%,P = 0.016). There were no differences in the adverse event rates between groups.

Conclusions: Combination therapy with metformin and mitiglinide is effective and safe for the treatment of patients with type 2 diabetes who have inadequate glycemic control with metformin monotherapy.(J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00023.x, 2010)
The effects of dexamethasone and prednisolone on pituitary and ovarian function in the mare
Authors: FERRIS R. A. , McCUE P. M.
Published: April 2010

Reasons for performing study:Persistent mating induced endometritis is among the most common causes of infertility in the mare. Recently, improved pregnancy rates have been reported when corticosteroids were administered to ‘problem mares’ specifically, to modulate the post mating inflammatory response; however, the effect of treatment on pituitary and ovarian function requires further study.

Objectives:To evaluate the effects of prolonged treatment with glucocorticoids on pituitary and ovarian function.

Methods:Eighteen cycling Quarter Horse mares in early oestrus were assigned randomly to one of 3 treatment groups: dexamethasone 0.05 mg/kg bwt i.v. twice a day, prednisolone 0.5 mg/kgper ostwice a day, or placebo for 5 days. Mares were examined by ultrasound daily to evaluate reproductive function. Blood samples were collected daily to measure luteinising hormone (LH), progesterone and cortisol levels.

Results:Dexamethasone treatment caused greater (P<0.05) suppression of endogenous cortisol concentration (9.4 ± 1.1 ng/ml) compared to prednisolone‐ (41.9 ± 4.0 ng/ml) or placebo‐treated mares (32.4 ± 3.8 ng/ml). After 24 h, mares treated with dexamethasone exhibited lower uterine oedema scores than prednisolone‐ or placebo‐treated mares. An ovulation rate of 40% was observed in dexamethasone‐treated mares (2/5) compared to 83% for prednisolone (5/6) and 100% for placebo‐treated (6/6) mares. An absence of a LH surge was noted in 3 of 5 dexamethasone‐treated mares and one of 6 prednisolone‐treated mares.

Conclusions:Repeated administration of dexamethasone to mares in oestrus is associated with decreased uterine oedema, suppression of LH and a high rate of ovulation failure. It is recommended that dexamethasone treatment is limited to only 1 or 2 days and that a lower dose is considered in the management of persistent mating induced endometritis to avoid potential adverse affects on reproductive function.
Lateralised motor behaviour leads to increased unevenness in front feet and asymmetry in athletic performance in young mature Warmblood horses
Authors: Van HEEL M. C. V. , Van DIERENDONCK M. C. , KROEKENSTOEL A. M. , BACK W.
Published: April 2010

Reason for performing study:Foot stance in grazing significantly influences hoof conformation and development from foal to yearling age.

Objectives:To conduct a longitudinal study to establish if the relationship between motor laterality and uneven front feet persisted in 3‐year‐old horses at the time of studbook selection and to investigate if such laterality and unevenness might influence the horses' ability to perform symmetrically while trotting, cantering and free jumping.

Methods:Seventeen clinically sound but untrained (with only minimal experience of handling) and sound Warmblood horses that had participated in a previous study were assessed as per the protocol reported. Laterality was tested in a preference test (PT) andz‐values were calculated for analysis purposes. Laterality and hoof unevenness were related to both relative limb length and relative head size, while the ability to perform symmetrically was tested in free trot‐canter transitions and free jumping exercises. Differences in performance between horses with and without a limb preference in the PT and those with ‘uneven’ and ‘even’ feet were tested for differences in performance metrics using Students'ttest, while linearity was tested using a regression analysis (P<0.05).

Results:Significant laterality was still present in 24% of the 3‐year‐old horses and the relationship between laterality and uneven feet pairs was stronger than at foal and yearling stages. Horses with significant motor laterality had almost 4 times more unevenness, a smaller head and longer limbs and the relationship between body conformation and laterality was still present. There was a strong linear relation between unevenness, laterality and a bias or side preference for trot‐canter transitions. However, this relationship was not significant during the free jumping exercise.

Conclusion:Motor laterality and uneven feet pairs were still present and significantly related in the 3‐year‐old horses and both variables were also strongly related to sidedness in trot‐canter transitions.

Potential relevance:Warmblood studbooks should include quantitative data on laterality at the time of studbook admission as part of the selection criteria.
CFD-Based Design of Microtubular Solid Oxide Fuel Cells
Authors: Cordiner Stefano , Mariani Alessandro , Mulone Vincenzo
Published: April 2010

Microtubular solid oxide fuel cells (MT-SOFCs) are interesting for portable and auxiliary power units energy production systems, due to their extremely fast startup time. However, a single cell provides power in the range of 1 W, thus the number of microtubes to reach a kW scale is relevant and packaging design issues arise also. In this paper a specifically developed design procedure is presented to face with system issues and bringing into account fluid-dynamic and thermal influence on system performance. The procedure also simplifies the stack manifold design by means of a modular scale-up procedure starting from a basic optimized configuration. To this aim, a computational fluid dynamics (CFD) model has been integrated with specific models for fuel cell simulation and then validated with tailored experimental data by varying operating conditions in terms of fuel utilization and electric load. A comprehensive three–dimensional (3D) thermal-fluid-dynamic model has then been applied to the analysis of both micro-assembly (i.e., 15 tube assembly) and midi-assembly (up to 45 tubes), showing an important role of local phenomena as current homogeneity and reactant local concentration that have a strong influence on power density and temperature distribution. Microreactor power density in the range of 0.3 kW/l have been demonstrated and a specific manifold design has been realized paving the way toward a modular realization of a 1 kW MT-SOFC.
Buoyancy Driven Heat Transfer of Nanofluids in a Tilted Enclosure
Authors: Kahveci Kamil
Published: April 2010

Buoyancy driven heat transfer of water-based nanofluids in a differentially heated, tilted enclosure is investigated in this study. The governing equations (obtained with the Boussinesq approximation) are solved using the polynomial differential quadrature method for an inclination angle ranging from 0 deg to 90 deg, two different ratios of the nanolayer thickness to the original particle radius (0.02 and 0.1), a solid volume fraction ranging from 0% to 20%, and a Rayleigh number varying from 104 to 106. Five types of nanoparticles, Cu, Ag, CuO, Al2O3, and TiO2 are taken into consideration. The results show that the average heat transfer rate from highest to lowest is for Ag, Cu, CuO, Al2O3, and TiO2. The results also show that for the particle radius generally used in practice (β=0.1 or β=0.02), the average heat transfer rate increases to 44% for Ra=104, to 53% for Ra=105, and to 54% for Ra=106 if the special case of θ=90 deg, which also produces the minimum heat transfer rates, is not taken into consideration. As for θ=90 deg, the heat transfer enhancement reaches 21% for Ra=104, 44% for Ra=105, and 138% for Ra=106. The average heat transfer rate shows an increasing trend with an increasing inclination angle, and a peak value is detected. Beyond the peak point, the foregoing trend reverses and the average heat transfer rate decreases with a further increase in the inclination angle. Maximum heat transfer takes place at θ=45 deg for Ra=104 and at θ=30 deg for Ra=105 and 106.
Determination of Time-Delay Parameters in the Dual-Phase Lagging Heat Conduction Model
Authors: Ordóñez-Miranda J. , Alvarado-Gil J. J.
Published: April 2010

The study of thermal transport based on the dual-phase lagging model involves not only the well known thermal properties but also two additional time parameters. Those parameters permit to take into account the thermal inertia and the microstructural interactions of the media in such a way that they establish the nonsimultaneity between temperature changes and heat flux. In the dual-phase lagging model, heat transport phenomena are extremely sensitive not only to the size of each time parameter but also to the relative size of them. In order to obtain useful and reliable results, it is important to develop methodologies for the determination of those time parameters. Additionally it is necessary to count with tools that allow evaluating easily the sensitivity of the temperature and heat to the changes in those time parameters. In this work, a system formed by a semi-infinite layer in thermal contact with a finite one, which is excited by a modulated heat flux, is studied. When the thermal effusivities of the layers are quite different, it is shown that a frequency range can be found in which the normalized amplitude and phase of the spatial component of the oscillatory surface temperature show strong oscillations. This behavior is used to obtain explicit formulas for determining simultaneously the time parameters as well as additional thermal properties of the finite layer, under the framework of the dual-phase lagging model of heat conduction. The limits of the corresponding equations for single-phase lagging models of heat conduction are also discussed.
Effects of Insulated and Isothermal Baffles on Pseudosteady-State Natural Convection Inside Spherical Containers
Authors: Duan Yuping , Hosseinizadeh S. F. , Khodadadi J. M.
Published: April 2010

The effects of insulated and isothermal thin baffles on pseudosteady-state natural convection within spherical containers were studied computationally. The computations are based on an iterative, finite-volume numerical procedure using primitive dependent variables. Natural convection effect is modeled via the Boussinesq approximation. Parametric studies were performed for a Prandtl number of 0.7. For Rayleigh numbers of 104, 105, 106, and 107, baffles with three lengths positioned at five different locations were investigated (120 cases). The fluid that is heated adjacent to the sphere rises replacing the colder fluid, which sinks downward through the stratified stable thermal layer. For high Ra number cases, the hot fluid at the bottom of the sphere is also observed to rise along the symmetry axis and encounter the sinking colder fluid, thus causing oscillations in the temperature and flow fields. Due to flow obstruction (blockage or confinement) effect of baffles and also because of the extra heating afforded by the isothermal baffle, multi-cell recirculating vortices are observed. This additional heat is directly linked to creation of another recirculating vortex next to the baffle. In effect, hot fluid is directed into the center of the sphere disrupting thermal stratified layers. For the majority of the baffles investigated, the Nusselt numbers were generally lower than the reference cases with no baffle. The extent of heat transfer modification depends on Ra, length, and location of the extended surface. With an insulated baffle, the lowest amount of absorbed heat corresponds to a baffle positioned horizontally. Placing a baffle near the top of the sphere for high Ra number cases can lead to heat transfer enhancement that is linked to disturbance of the thermal boundary layer. With isothermal baffles, heat transfer enhancement is achieved for a baffle placed near the bottom of the sphere due to interaction of the counterclockwise rotating vortex and the stratified layer. For some high Ra cases, strong fluctuations of the flow and thermal fields indicating departure from the pseudosteady-state were observed.
Relationships of Viscosity With Contact Hardness and Modulus of Bone Matrix Measured by Nanoindentation
Authors: Kim Do-Gyoon , Huja Sarandeep S. , Lee Hye Ri , Tee Boon Ching , Hueni Sarah
Published: April 2010

Creep is an active form of time-dependent viscoelastic deformation that occurs in bone tissue during daily life. Recent findings indicate bone mineralization, which is involved in determining the elastic and plastic properties of bone matrix, can also contribute in controlling its viscoelastic property. Nanoindentation viscosity was used as a direct measure for the capacity of a material to resist viscous-like flow under loading. The objectives of this study were to examine (1) whether the nanoindentation viscosity obtained using the traditional viscoelastic Voigt model can describe creep response of bone matrix and (2) how the nanoindentation viscosity is related to contact hardness and elastic modulus. The Voigt model accurately described the creep behavior of bone matrix (r2>0.96, p<0.001). The nanoindentation viscosity had strong relationships with nanoindentation contact hardness (r2=0.94, p<0.001) and modulus (r2=0.83, p<0.001) independent of tissue ages of osteonal bone matrix. The strong positive relationships of nanoindentation viscosity with contact hardness and modulus can be interpreted as increases in the mineral portion of bone matrix may limit the interfibril motion of collagen while enhancing the mechanical stability of bone. We suggest that previous nanoindentation results can be reanalyzed to characterize the viscoelastic creep using the Voigt model.