bluuebunny/crossref_metadata_2025 huggingface dataset:
CpG-B Oligodeoxynucleotides Inhibit TLR-Dependent and -Independent Induction of Type I IFN in Dendritic Cells
Authors: Liu Yi C. , Gray Reginald C. , Hardy Gareth A. D. , Kuchtey John , Abbott Derek W. , Emancipator Steven N. , Harding Clifford V.
Published: February 2010

CpG oligodeoxynucleotides (ODNs) signal through TLR9 to induce type I IFN (IFN-αβ) in dendritic cells (DCs). CpG-A ODNs are more efficacious than CpG-B ODNs for induction of IFN-αβ. Because IFN-αβ may contribute to autoimmunity, it is important to identify mechanisms to inhibit induction of IFN-αβ. In our studies, CpG-B ODN inhibited induction of IFN-αβ by CpG-A ODN, whereas induction of TNF-α and IL-12p40 by CpG-A ODN was not affected. CpG-B inhibition of IFN-αβ was observed in FLT3 ligand-induced murine DCs, purified murine myeloid DCs, plasmacytoid DCs, and human PBMCs. CpG-B ODN inhibited induction of IFN-αβ by agonists of multiple receptors, including MyD88-dependent TLRs (CpG-A ODN signaling via TLR9, or R837 or Sendai virus signaling via TLR7) and MyD88-independent receptors (polyinosinic:polycytidylic acid signaling via TLR3 or ds break-DNA signaling via a cytosolic pathway). CpG-B ODN did not inhibit the IFN-αβ positive feedback loop second-wave IFN-αβ, because IFN-αβ–induced expression of IFN-αβ was unaffected, and CpG-B inhibition of IFN-αβ was manifested in IFN-αβR−/− DCs, which lack the positive feedback mechanism. Rather, CpG-B ODN inhibited early TLR-induced first wave IFN-α4 and IFN-β. Chromatin immunoprecipitation revealed that association of IFN regulatory factor 1 with the IFN-α4 and IFN-β promoters was induced by CpG-A ODN but not CpG-B ODN. Moreover, CpG-A–induced association of IFN regulatory factor 1 with these promoters was inhibited by CpG-B ODN. Our studies demonstrate a novel mechanism of transcriptional regulation of first-wave IFN-αβ that selectively inhibits induction of IFN-αβ downstream of multiple receptors and may provide targets for future therapeutic inhibition of IFN-αβ expression in vivo.
IL-1 Receptor Antagonist Protects against Placental and Neurodevelopmental Defects Induced by Maternal Inflammation
Authors: Girard Sylvie , Tremblay Luc , Lepage Martin , Sébire Guillaume
Published: February 2010

The precise role of maternal bacterial infection and inflammation occurring at the end of gestation is a controversial matter. Although it is recognized as an independent risk factor for neurodevelopmental diseases such as cerebral palsy, mental deficiency, and autism, it remains unclear whether it is causal or simply associated with the diseases. In this study, we demonstrate that IL-1 plays a key role in mediating severe placental damage and neurodevelopmental anomalies in offspring. Our results show that end of gestation exposure of pregnant rats to systemic microbial product (LPS) triggers placental inflammation and massive cell death, fetal mortality, and both forebrain white matter and motor behavioral alterations in the offspring. All these effects are alleviated by the coadministration of IL-1 receptor antagonist with LPS, suggesting a possible protective treatment against human placental and fetal brain damage.
Desenvolvimento das habilidades motoras finas no primeiro ano de vida
Authors: Arias Amabile Vessoni , Gonçalves Vanda Maria Gimenes , Campos Denise , Santos Denise Castilho Cabrera , Goto Maura Mikie Fukujima , Zanelli Thatiane Moura Campos
Published: February 2010

Estudo realizado a partir de revisão da literatura teve por objetivo descrever as principais etapas do desenvolvimento das habilidades motoras finas no primeiro ano de vida, como o alcance, a preensão e a manipulação dos objetos. Enfatizou-se o aspecto evolutivo das aquisições que surgem progressivamente, em associação com a maturidade do sistema nervoso, musculoesquelético e com a experiência. Além disso, pôde-se constatar grande especificidade nos processos de desenvolvimento motor. O conhecimento detalhado das habilidades motoras finas típicas torna a percepção do examinador mais apurada para reconhecer e interpretar o desenvolvimento atípico possibilita o encaminhamento para a estimulação de habilidades específicas, auxilia na estruturação do programa de estimulação e na observação os ganhos advindos deste assim como facilita a orientação dos pais durante o programa.
Reliability of ultrasonography to detect synovitis in rheumatoid arthritis: A systematic literature review of 35 studies (1,415 patients)
Authors: Cheung Peter P. , Dougados Maxime , Gossec Laure
Published: February 2010

Objective

To perform a systematic review on the reliability of ultrasonographic (US) synovitis detection in rheumatoid arthritis (RA) by B‐mode and power Doppler (PD) in image acquisition and still‐image interpretation. US is a sensitive method for synovitis detection. However, reliability is still a key concern.

Methods

Articles reporting any US reliability results for synovitis in RA in PubMed, EMBase, the Cochrane Library, and meeting abstracts were selected. Data were extracted from the collection of data on US synovitis detection (either qualitatively [binary] or semiquantitatively [0–3 scale], for intraobserver and interobserver reliability in B‐mode and PD, and for image acquisition and still‐image interpretation). The type of joints tested, the experience of the ultrasonographer, and the quality of the studies were assessed. Data analysis involved descriptive and graphic interpretation of reliability and its potential determinants.

Results

Thirty‐five studies (12 for B‐mode, 11 for PD, or 12 for both) with a total of 1,415 patients were analyzed. Intraobserver and interobserver reliability for still images in B‐mode and PD was high (κ = 0.5–1.0 [14,991 joints] for intraobserver reliability for B‐mode, κ = 0.59–1.0 [14,934 joints] for PD, κ = 0.49–1.0 [3,138 joints] for interobserver for B‐mode, and κ = 0.66–1.0 [3,325 joints] for PD). Interobserver reliability for image acquisition in both US modes was lower than still‐image interpretation (κ = 0.22–0.95). Few studies reported intraobserver image acquisition reliability.

Conclusion

Intraobserver and interobserver reliability of still‐image interpretation was high, especially for PD, in published studies involving highly trained observers. However, reliability of acquisition of US should be further assessed.
Prevalence, severity, and clinical correlates of pain in patients with systemic sclerosis
Authors: Schieir Orit , Thombs Brett D. , Hudson Marie , Boivin Jean‐François , Steele Russell , Bernatsky Sasha , Hanley James , Baron Murray ,   Canadian Scleroderma Research Group
Published: February 2010

Objective

Large descriptive studies of pain in systemic sclerosis (SSc) are lacking. The present study estimated prevalence, severity, and associations between SSc clinical variables and pain in all patients with SSc and in limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets.

Methods

Patients enrolled in a multicenter SSc registry (n = 585) completed a standardized clinical assessment and questionnaires about their physical and psychosocial health, including a pain severity numerical rating scale (NRS; range 0–10). Pain prevalence and severity were estimated with descriptive statistics. Crude and adjusted associations between specific SSc clinical variables and pain were estimated with linear regression for the entire group and by SSc subtype.

Results

Of the patients, 484 (83%) reported pain (268 [46%] mild pain [NRS 1–4], 155 [27%] moderate pain [NRS 5–7], and 61 [10%] severe pain [NRS 8–10]). More frequent episodes of Raynaud's phenomenon, active ulcers, worse synovitis, and gastrointestinal (GI) symptoms were associated with pain in multivariate analysis adjusting for demographic variables, depressive symptoms, and comorbid conditions. Patients with dcSSc reported only slightly higher mean ± SD pain than those with lcSSc (dcSSc 3.9 ± 2.8 versus lcSSc 3.4 ± 2.7; Hedges's g = 0.18, P = 0.05). Regression estimates did not differ significantly between SSc subsets.

Conclusion

Pain symptoms were common in the present study of patients with SSc and were independently associated with more frequent episodes of Raynaud's phenomenon, active ulcers, worse synovitis, and GI symptoms. Subsetting by extent of skin involvement was only minimally related to pain severity and did not affect associations with clinical variables. More attention to pain and how to best manage it is needed in SSc.
Fish movements: the introduction pathway for topmouth gudgeon Pseudorasbora parva and other non‐native fishes in the UK
Authors: Copp G. H. , Vilizzi L. , Gozlan R. E.
Published: February 2010

The contamination of fish consignments (for stocking or aquaculture) is a major pathway by which non‐native organisms, including fish, are introduced to new areas. One of the best examples of this is the topmouth gudgeon Pseudorasbora parva, which was accidentally imported into Romania and then throughout Europe in consignments of Asian carp species.

The introduction and spread of topmouth gudgeon in the UK has been linked to imports and movements of the ornamental variety (golden orfe) of ide Leuciscus idus. To examine this hypothesis, relationships between authorized movements of both native and non‐native fish species (in particular ide) and the occurrence in England of topmouth gudgeon were tested at the 10×10 km scale.

Topmouth gudgeon occurrence in the wild was significantly correlated with the trajectories of movements of ornamental fish species (ide/orfe, sunbleak Leucaspius delineatus) as well as a few non‐ornamental fish species (European catfish Silurus glanis, Atlantic salmon Salmo salar and grass carp Ctenopharyngodon idella).

These results highlight the mechanism by which non‐native fish species disperse from the point of first introduction, and especially that movements of fish within the country represent an important mechanism for accidental introductions of non‐native species. © Crown copyright 2010. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd.
Two‐year clinical and radiographic results with combination etanercept–methotrexate therapy versus monotherapy in early rheumatoid arthritis: A two‐year, double‐blind, randomized study
Authors: Emery Paul , Breedveld Ferdinand , van der Heijde Désirée , Ferraccioli Gianfranco , Dougados Maxime , Robertson Deborah , Pedersen Ronald , Koenig Andrew S. , Freundlich Bruce
Published: February 2010

Objective

To evaluate how continuation of and alterations to initial year 1 combination etanercept–methotrexate (MTX) therapy and MTX monotherapy regimens affect long‐term remission and radiographic progression in early, active rheumatoid arthritis.

Methods

Subjects were randomized at baseline for the entire 2‐year period; those who completed 1 year of treatment with combination or MTX monotherapy entered year 2. The original combination group either continued combination therapy (the EM/EM group; n = 111) or received etanercept monotherapy (the EM/E group; n = 111) in year 2; the original MTX monotherapy group either received combination therapy (the M/EM group; n = 90) or continued monotherapy (the M/M group; n = 99) in year 2. Efficacy end points included remission (a Disease Activity Score in 28 joints [DAS28] <2.6) and radiographic nonprogression (change in the modified Sharp/van der Heijde score ≤0.5) at year 2. A last observation carried forward analysis from the modified intention‐to‐treat population (n = 398) and a post hoc nonresponder imputation (NRI) analysis (n = 528) were performed for remission.

Results

At year 2, DAS28 remission was achieved by 62/108, 54/108, 51/88, and 33/94 subjects in the EM/EM, EM/E, M/EM, and M/M groups, respectively (P< 0.01 for the EM/EM and M/EM groups versus the M/M group). This effect was corroborated by a more conservative post hoc 2‐year NRI analysis, with remission observed in 59/131, 50/134, 48/133, and 29/130 of the same respective groups (P< 0.05 for each of the EM/EM, EM/E, and M/EM groups versus the M/M group). The proportions of subjects achieving radiographic nonprogression (n = 360) were 89/99, 74/99, 59/79, and 56/83 in the EM/EM (P< 0.01 versus each of the other groups), EM/E, M/EM, and M/M groups, respectively. No new safety signals or between‐group differences in serious adverse events were seen.

Conclusion

Early sustained combination etanercept–MTX therapy was consistently superior to MTX monotherapy. Combination therapy resulted in important clinical and radiographic benefits over 2 study years, without significant additional safety risk.
Sensing the mechanical state of the axoneme and integration of Ca2+ signaling by outer arm dynein
Authors: King Stephen M.
Published: February 2010

Axonemal dyneins have been demonstrated to monitor the mechanical state of the axoneme and must also alter activity in response to various signaling pathways. The central pair/radial spoke systems are clearly involved in controlling inner dynein arm function; however, the mechanisms by which the outer dynein arm transduces regulatory signals appear quite distinct at the molecular level. In Chlamydomonas, these regulatory components include thioredoxins involved in response to redox changes, molecules that tether the γ heavy‐chain motor unit to the A‐tubule of the outer doublet and a Ca2+‐binding protein that controls the structure of the γ heavy‐chain N‐terminal domain. Together, these studies now suggest that the γ heavy chain acts as a key regulatory node for controlling outer arm function in response to alterations in curvature and ligand binding. Furthermore, they allow us to propose a testable molecular mechanism by which altered Ca2+ levels might lead to a change in ciliary waveform by controlling whether one heavy chain of outer arm dynein acts as a microtubule translocase or as an ATP‐dependent brake that limits the amount of interdoublet sliding. © 2010 Wiley‐Liss, Inc.
Synthesis of 1,3‐Diphospha‐2,3‐dihydro‐1H‐phenalenes
Authors: Tarasevych Arkadii , Shevchenko Igor , Rozhenko Alexander B. , Röschenthaler Gerd‐Volker
Published: February 2010

The reaction of 1,8‐dilithionaphthalene (1) with methylenebis[(dialkylamino)chlorophosphanes] [R2N(Cl)PCH2P(Cl)NR2; R = Me (2a), Et (2b)] leads to the formation of new heterocyclic compounds, 1,3‐diphospha‐2,3‐dihydro‐1H‐phenalenes 3a,b as a mixture of cis and trans isomers. DFT calculations indicate that the cis isomers are thermodynamically more stable by about 1–3 kcal/mol than the trans isomers. Compounds 3a,b can be converted into dithio the derivatives 5a,b and the borane complexes 6a,b, which were characterized by NMR spectroscopy and investigated by X‐ray diffraction analysis. The dialkylamino groups in 3 can be substituted by chlorine to give the chlorophosphane 7.
Thermal Rearrangements of (Arylimino)diaziridines by Simultaneous Cascades of Pericyclic Reactions
Authors: Quast Helmut , Ross Karl‐Heinz , Philipp Gottfried
Published: February 2010

(Arylimino)diaziridines rearrange in several cascade reactions at temperatures 60–100 °C. Those that possess unoccupied ortho positions yield fluorescent 3‐amino‐2H‐indazoles and 2‐amino‐1H‐benzimidazoles. If both ortho positions are blocked by methyl groups, indazoles are not formed and deeply yellow 2‐imino‐2,3‐dihydro‐3aH‐benzimidazoles are formed, which partly dimerize through Diels–Alder reaction or regenerate the aromatic system by formal loss of CH2. In addition, one of the methyl groups of 2,6‐dimethylphenyl rings is involved in a [1,7] H shift affording orthoquinonoid intermediates which undergo 1,6‐electrocyclization to furnish 2‐amino‐3,4‐dihydroquinazolines. The formation of five‐membered ring heterocycles is interpreted in terms of valence isomerization by [1,3] N shift to yield elusive 1‐aryl‐3‐iminodiaziridines as first step. These immediately experience triaza‐Cope rearrangement to benzimidazole derivatives or electrocyclic opening of the N–C bond to generate conjugated azomethine imines (1,5‐dipoles), followed by their 1,5‐electrocyclization to indazoles. First‐order rate constants of the decay of (arylimino)diaziridines refer to the [1,3] N shifts as rate‐determining steps. They are larger than the corresponding rate constants for alkylsubstituted iminodiaziridines.
Journal of Bone and Mineral Research
Authors: DR. Briançon D. , D'Aranda P. , Quillet P. , Duplan B. , Chapuy M. C. , Arlot M. , Meunier P. J.
Published: February 2010

To assess whether an interval of a few hours would be advisable between an intake of sodium fluoride (NaF) and that of calcium salts when treating osteoporotic patients with vertebral collapse, we carried out three pharmacokinetic studies in 12 healthy fasting volunteer subjects to compare the fluoride bioavailability provided by NaF alone and NaF combined with two calcium salts. The results were as follows: (1) When NaF is accompanied by calcium, the fluoride peak level is lower and delayed. (2) Fluoride absorption varied greatly among individuals in both experiments, but none of the 6 subjects proved to be nonabsorbers. (3) The areas under the curves obtained with each of the three preparations were not significantly different, but 24-h urinary fluoride was significantly lower in volunteers receiving simultaneously NaF and calcium salts than in volunteers receiving only NaF.
Journal of Bone and Mineral Research
Authors: Dr. Zerwekh Joseph E. , Padalino Paulette K. , Pak Charles Y. C. , Morris Alan C. , Gottschalk Frank
Published: February 2010

We examined the effect of fluoride (F) on intracellular ionic calcium [Ca2+]i in normal human osteoblasts maintained in culture. Cells were grown on glass coverslips to near-confluency and loaded with the Ca-sensitive dye, fura-2AM. Fluorescence changes were monitored in single cells using an inverted microscope coupled by fiberoptic to a microspectrofluoremeter. The addition of F (100 ng/mL) to the medium promoted a rapid and significant increase in free [Ca2+]i from a resting level of 245 ± 36 SE nM to a peak concentration of 440 ± 51 nM (p < 0.04). This increase in [Ca2+]i began at 10–20 s after addition of F and was maximal by 30 s. Intracellular [Ca2+]i levels then returned to near resting values by 60–80 s after F addition. This response was evident with as little as 25 ng/ml of fluoride and was dose dependent up to 500 ng/ml. At concentrations greater than 500 ng/ml, there appeared to be an attenuation of the rise in [Ca2+]i. The observed rise in [Ca2+]i was dependent on extracellular calcium since lowering extracellular calcium concentration or incubation with calcium channel blockers abolished the response. This observation supports a role of increased [Ca2+]i as one of the initial events of fluoride on action osteoblasts.
Journal of Bone and Mineral Research
Authors: Schnitzler Christine M. , Mesquita Julia M. , Gear Ann K. , Robson Heather J. , Wing Jeffrey R. , Smyth Amelia E.
Published: February 2010

We attempted to identify risk factors for the development of lower limb stress fractures during fluoride therapy for osteoporosis (OP). We compared 18 patients who developed 41 such fractures (26 periarticular, 6 femoral neck, 5 long bone shaft, 1 greater trochanter and 3 pubic rami fractures) during fluoride therapy, with 24 similarly treated patients who did not develop stress fractures. Treatment consisted of sodium fluoride 0.99 mg/kg per day, elemental calcium 1 g/day, and vitamin D. We obtained a previous fracture history, annual radiographs of the spine (fractures), hands (metacarpal cortical index, MCI) and pelvis (Singh index, femoral cortical index), three-monthly serum fluoride and alkaline phosphatase levels, and pretreatment transiliac bone biopsies (routine histomorphometry). The stress fracture group was found to have, before treatment: lower MCI (p < 0.05), lower trabecular bone volume (p < 0.05), a lower number of trabeculae (p < 0.05), greater trabecular separation (p < 0.05), less extensive eroded surfaces (p < 0.05), a lower double/single tetracycline label ratio (p < 0.05); and during treatment: more new spinal fractures (p < 0.05) and higher serum alkaline phosphatase levels (p < 0.01). We conclude that stress fracture patients had more severe trabecular and cortical OP and possibly a poorer bone-forming capacity before therapy than patients without stress fractures. We suspect that fluoride therapy may temporarily further weaken bone and so lead to stress fractures in severely osteoporotic patients. To prevent stress fractures we recommend that fluoride therapy be commenced before OP is profound and that lower fluoride dosage, or intermittent therapy be employed in patients with cortical as well as trabecular OP, especially when alkaline phosphatase levels rise above 1.6 times the upper limit of normal, or when new spinal fractures develop.
Journal of Bone and Mineral Research
Authors: Melton L. Joseph
Published: February 2010

Age-related fractures, especially hip fractures, produce sufficient morbidity and mortality to make osteoporosis a disease worth preventing, and accurate techniques exist to identify groups at high risk of fracture by virtue of low bone mass. While the need for prevention is evident, no specific program of fluoride use for this purpose has been devised, and epidemiologic data provide little support for the notion that exposure to fluoride reduces hip fracture incidence. At present, fluoride cannot be recommended as a prophylactic agent for the fractures that are the primary adverse health outcome of osteoporosis.
Journal of Bone and Mineral Research
Authors: Kraenzlin M. E. , Kraenzlin C. , Farley S. M. G. , Fitzsimmons R. J. , Baylink D. J.
Published: February 2010

In this study, the relationship between fluoride pharmacokinetics and the response in spinal bone density to fluoride treatment was studied in 14 patients with primary osteoporosis treated with fluoride for at least 1 year. Serum concentrations and urinary excretion of fluoride were determined after ingestion of 10 mg fluoride as monofluorophosphate. The pharmacokinetic parameters were calculated according to a linear one-compartment open model. The fasting serum fluoride level was 8.8 ± 0.98 μmol/liter. The peak serum fluoride level was 20.5 ± 1.4 μmol/liter and was reached within 2 h after ingestion of fluoride. When the patients were divided into good and poor responders, based on whether they did or did not exhibit a change in spinal bone density of 13 mg/cc per year or more, we found that good responders had decreased renal fluoride clearance (−62 ± 13%, p < .02), increased maximum change in serum fluoride (+38 ± 18%, p < .01), increased extrarenal clearance (+62 ± 57%, p < .05) and increased change in serum alkaline phosphatase (ALP) (+241 ± 169%, p < 0.02) compared with poor responders. Our data suggest that one factor accounting for a good response is a relatively high serum level of fluoride. However, although the maximum change in serum fluoride was greater in good responders compared with poor responders, variations in fluoride levels could not explain all of the variation in spinal bone density. Therefore, we propose that in addition to differences in serum fluoride, other factors are also responsible for the good response.
Journal of Bone and Mineral Research
Authors: Professor Carter Dennis R. , Beaupré Gary S.
Published: February 2010

Bone mass and architecture in appendicular and most axial sites is controlled primarily by the tissue-loading history. We introduce a conceptual framework for understanding how fluoride treatment alters this control and can cause systemic increases in bone mass. Due to possible adverse influences of fluoride on the mineralized tissue physical characteristics, however, the increase in bone mass does not necessarily result in an increase in bone strength. Using engineering analyses of bone trabeculae, we calculate the losses in trabecular strength which can be caused by the presence of hypomineralized or hypermineralized fluorotic tissue. Significant increases in bone volume fraction and bone mass may be required to overcome these strength deficits.
Journal of Bone and Mineral Research
Authors: DR. Ekstrand Jan , Spak Carl-Johan
Published: February 2010

This report reviews some aspects of fluoride pharmacokinetics in relation to the treatment of osteoporosis. The bioavailability of conventional plain NaF tablets has been shown to be close to 100, for sustained-release NaF tablets close to 90%, and for enteric-coated NaF tablets 65%. The simultaneous intake of food and/or calcium tablets reduces the bioavailability by 30 to 40%. Fluoride renal clearance is influenced by both urinary pH and flow and the clinical consequences of this is discussed. Studies on plasma kinetics of fluoride during chronic fluoride intake suggests that a plasma sample taken at mid-dosage intervals will give reproducible “mean steady-state” levels. It is suggested that improvements of the clinical benefit of fluoride therapy in osteoporosis might be achieved if the dosage regimen were based on the pharmacokinetic properties of the fluoride preparation used as well as plasma fluoride monitoring.
Journal of Bone and Mineral Research
Authors: Okuda A. , Kanehisa J. , Heersche J. N. M.
Published: February 2010

It is not clear to what extent the increased bone mass observed in vertebral trabecular bone of fluoride-treated mammals is a consequence of effects of fluoride on the number and activity of osteoclasts or of osteoblasts. In the present communication, we have analyzed the effects of NaF on the activity of isolated rabbit osteoclasts cultured on thin slices of devitalized compact bovine bone. Osteoclastic resorption was quantitated by counting the number of resorption lacunae and measuring their surface area and their depth using scanning electron microscopy. Our results show that NaF in concentrations of 0.5–1.0 mM decreased the number of resorption lacunae made by individual osteoclasts and decreased the resorbed area per osteoclast. We argue that the concentration of fluoride in these experiments may be within the range “seen” by osteoclasts in mammals treated for prolonged periods with approximately 1 mg of NaF/kg body weight (bw) per day.
Journal of Bone and Mineral Research
Authors: Boivin Georges , Chavassieux Pascale , Chapuy Marie-Claire , Meunier Pierre J. , Baud Charles A.
Published: February 2010

Histomorphometric analysis of undecalcified sections was performed in transiliac biopsy cores taken from 29 patients (16 men, 13 women, aged 51 ± 17 years) suffering from skeletal fluorosis due to chronic exposure to fluoride. The origin of the exposure, known in 20 patients, was either hydric (endemic or sporadic), or industrial, or in a few cases iatrogenic. Measured on calcined bone using a specific ion electrode, bone fluoride content was significantly high in each specimen (mean ± SD: 0.79 ± 0.36% of bone ash) as compared to control values (< 0.10%). The radiologically evident osteosclerosis observed in each patient was confirmed by the significant increase of cancellous bone volume (40.1 ± 11.2 vs. 19.0 ± 2.8% in controls, p < 0.0001). There were significant increases in cortical width (1292 ± 395 vs. 934 ± 173 μm, p < 0.0001) and porosity (14.4 ± 6.4 vs. 6.5 ± 1.7%, p < 0.002), but without reduction of cortical bone mass. Osteoid parameters were significantly increased in fluorotic patients. The increase in cancellous osteoid perimeter was almost threefold greater than that noted in cancellous eroded perimeter. The fluorotic group had a greater number of osteoblasts than controls, with a very high proportion of flat osteoblasts. In 15 patients doubly labeled with tetracycline, the mineral apposition rate was significantly decreased, while mineralization lag time significantly increased. Bone formation rate and adjusted apposition rate were significantly decreased in skeletal fluorosis. Cancellous wall width was normal in fluorosis but the formation period and active formation period were significantly increased. Skeletal fluorosis is thus characterized by an unbalanced coupling in favor of bone formation, and also by a great number of osteoblasts with a high proportion of flat osteoblasts. These osteoblasts have a very increased formation period mainly due to a prolonged inactive formation period. Our results support the view that fluoride may have a dual effect on osteoblasts: an increased birthrate at the tissue level, and a toxic effect at the individual cell level. The addition of these two effects represents, however, a marked increase of bone formation at the organ level.
Cross‐cutting moraines reveal evidence for North Atlantic influence on glaciers in the tropical Andes
Authors: Smith Jacqueline A. , Rodbell Donald T.
Published: February 2010

Surface exposure dating of boulders on an exceptionally well‐preserved sequence of moraines in the Peruvian Andes reveals the most detailed record of glaciation heretofore recognised in the region. The high degree of moraine preservation resulted from dramatic changes in the flow path of piedmont palaeoglaciers at the southern end of the Cordillera Blanca (10° 00′ S, 77° 16′ W), which, in turn, generated a series of cross‐cutting moraines. Sixty 10Be surface exposure ages indicate at least four episodes of palaeoglacier stabilisation (>65, ca. 65, ca. 32 and ca. 18–15 ka) and several minor advances or stillstands on the western side of the Nevado Jeulla Rajo massif. The absence of ages close to the global Last Glacial Maximum (ca. 21 ka) suggests that if an advance culminated at that time any resulting moraines were subsequently overridden. The timing of expanded ice cover in the central Peruvian Andes correlates broadly with the timing of massive iceberg discharge (Heinrich) events in the North Atlantic Ocean, suggesting a possible causal connection between southward migration of the Intertropical Convergence Zone during Heinrich events and a resultant increase in precipitation in the tropical Andes. Copyright © 2010 John Wiley & Sons, Ltd.
Heterodyne interferometric polarization coherent anti‐Stokes Raman scattering (HIP‐CARS) spectroscopy
Authors: Orsel K. , Garbacik E. T. , Jurna M. , Korterik J. P. , Otto C. , Herek J. L. , Offerhaus H. L.
Published: February 2010

We demonstrate a new technique that combines polarization sensitivity of the coherent anti‐Stokes Raman scattering (CARS) response with heterodyne amplification for background‐free detection of CARS signals. In this heterodyne interferometric polarization CARS (HIP‐CARS), the major drawbacks of polarization and heterodyne CARS are rectified. Using a home‐built picosecond optical parametric oscillator, we are able to address vibrational stretches between 600 and 1650 cm−1 and record continuous high‐resolution Raman equivalent HIP‐CARS spectra. Copyright © 2010 John Wiley & Sons, Ltd.
Corrosion behavior of polypyrrole/hydroxyapatite nanocomposite thin films electropolymerized on NiTi substrates in simulated body fluid
Authors: Torabi M. , Sadrnezhaad S. K.
Published: February 2010

Hydroxyapatite (HAp) nanoparticles synthesized via microwave irradiation. Polypyrrole (PPy)/HAp nanocomposite was obtained using electropolymerization on nitinol (Ni) titanium (Ti) substrates. Fourier transform infrared was employed to characterize the nanocomposite formation. Electrochemical properties of the nanocomposite were investigated using polarization and electrochemical impedance spectroscopy (EIS) in simulated body fluid (SBF, 37 ± 0.1 °C). It was concluded that the NiTi specimen coated with PPy/HAp nanocomposite, has higher corrosion resistance than the NiTi coated with pure PPy in the SBF; however, NiTi was better than both coated NiTi. EIS results confirmed corrosion properties. Also, EIS was used to predict the morphology of the coatings. It predicted fine and compact morphology of the nanocomposite that was confirmed using scanning electron microscopy.
Fatigue behaviour of welded joints from magnesium alloy (AZ31) according to the local strain concept
Authors: Karakas Ö. , Gülsöz A. , Kaufmann H. , Sonsino C. M.
Published: February 2010

In the present study, the results of fatigue tests with the magnesium alloy AZ31 (ISO‐MgAl3Zn1) in the material states base metal, heat affected zone and weld metal obtained under strain control at room temperature within a range from 2·102 to 5·106 cycles are presented. The fatigue behaviour was characterized by the Coffin–Manson–Basquin equations and the stress – strain behaviour by the Ramberg–Osgood equation. The data can be used to assess welded magnesium joints according to the local strain concept.
Inflammation and Parkinson's disease pathogenesis
Authors: Przedborski Serge
Published: February 2010

Inflammation is a neuropathological feature of parkinsonian brains and also in experimental models of the disease. It is believed that activated glial cells, which compose the majority of this inflammatory response contribute to the neurodegenerative process through the production of toxic molecules. Therapeutic strategies geared toward reducing inflammation and inhibiting the production of these glial‐derived toxic molecules may be a promising neuroprotective strategy for the treatment of Parkinson's disease and related conditions. © 2010 Movement Disorder Society
Examining Braak's hypothesis by imaging Parkinson's disease
Authors: Brooks David J.
Published: February 2010

In this review, in vivo patterns of structural, metabolic, and neurotransmitter binding changes revealed by imaging in both symptomatic Parkinson's disease (PD) and at‐risk subjects are compared with those predicted at different Braak stages. It is concluded that the dysfunction revealed by imaging in PD is only partially in line with the sequential ascending topography of Lewy body pathology reported by Braak, suggesting that neurons in different brain regions are likely to be selectively vulnerable to the presence of intracellular synuclein aggregates. © 2010 Movement Disorder Society
The behavior of α‐synuclein in neurons
Authors: Fortin Doris L. , Nemani Venu M. , Nakamura Ken , Edwards Robert H.
Published: February 2010

Despite considerable evidence linking α‐synuclein with membranes in vitro, it has proven difficult to demonstrate membrane association of the protein in vivo. α‐Synuclein localizes to the nerve terminal, but biochemical experiments have not revealed a tight association with membranes. To address the dynamics of the protein in live cells, we have used photobleaching and found that α‐synuclein exhibits high mobility, although distinctly less than an entirely soluble protein. Further, neural activity controls the distribution of α‐synuclein, causing its dispersion from the synapse. In addition to the presumed role of α‐synuclein dynamics in synaptic function, changes in its physiological behavior may underlie the pathological changes associated with Parkinson's disease. © 2010 Movement Disorder Society
Enhancing neuroplasticity in the basal ganglia: The role of exercise in Parkinson's disease
Authors: Petzinger Giselle M. , Fisher Beth E. , Van Leeuwen Jon‐Eric , Vukovic Marta , Akopian Garnik , Meshul Charlie K. , Holschneider Daniel P. , Nacca Angelo , Walsh John P. , Jakowec Michael W.
Published: February 2010

Epidemiological and clinical trials have suggested that exercise is beneficial for patients with Parkinson's disease (PD). However, the underlying mechanisms and potential for disease modification are currently unknown. This review presents current findings from our laboratories in patients with PD and animal models. The data indicate that alterations in both dopaminergic and glutamatergic neurotransmission, induced by activity‐dependent (exercise) processes, may mitigate the cortically driven hyper‐excitability in the basal ganglia normally observed in the parkinsonian state. These insights have potential to identify novel therapeutic treatments capable of reversing or delaying disease progression in PD. © 2010 Movement Disorder Society
The nonmotor symptoms of Parkinson's disease—An overview
Authors: Lim Shen‐Yang , Lang Anthony E.
Published: February 2010

Nonmotor symptoms (NMS) are very common in Parkinson's disease (PD) and may result in significant disability. The increased focus on these important clinical features represents a major advance in the care of PD patients. In this article, we provide an overview of recent developments in the field. © 2010 Movement Disorder Society
Therapeutic directions for Parkinson's disease
Authors: Shoulson Ira
Published: February 2010

The focus on disease‐modifying treatments and cures for Parkinson's disease (PD) has raised expectations for quantum leaps and overshadowed incremental gains that have been slowly achieved. Large multi‐center clinical trials such as DATATOP and PRECEPT keep on generating new knowledge that is relevant to clinical care as well as experimental therapeutics. The largely unforeseen relationship between circulating uric acid and the occurrence and progression of PD was developed and confirmed in these clinical trials. Systematic follow‐up of clinical trial cohorts after conclusion of the interventional phase provides added value that continues to inform about natural history, state and trait biomarkers, and genotype‐phenotype relationships. These efforts are enhanced by data mining, public reporting, and timely sharing of data and biological samples. © 2010 Movement Disorder Society
A molecular basis for the increased vulnerability of substantia nigra dopamine neurons in aging and Parkinson's disease
Authors: Chan C. Savio , Gertler Tracy S. , Surmeier D. James
Published: February 2010

Parkinson's disease (PD) is a common neurodegenerative disorder of unknown etiology. There is no cure or proven strategy for slowing the progression of the disease. Although there are signs of pathology in many brain regions, the core symptoms of PD are attributable to the selective degeneration of dopaminergic neurons in the substantia nigra pars compacta. A potential clue to the vulnerability of these neurons is an increasing reliance with age upon L‐type Ca2+channels with a pore‐forming Cav1.3 subunit to support autonomous activity. This reliance could pose a sustained stress on mitochondrial ATP generating oxidative phosphorylation, accelerating cellular aging and death. Systemic administration of isradipine, a dihydropyridine blocker of these channels, forces dopaminergic neurons in rodents to revert to a juvenile, L‐type Ca2+channel independent mechanism to generate autonomous activity. This “rejuvenation” confers protection against toxins that produce experimental Parkinsonism, pointing to a potential neuroprotective strategy for PD. Their decades‐long track record of safe use in the treatment of hypertension makes dihydropyridines particularly attractive as a therapeutic tool in PD. © 2010 Movement Disorder Society
First trimester maternal serum ADAM12s levels in twin pregnancies
Authors: Linskens I. H. , Twisk J. W. R. , Blankenstein M. A. , van Vugt J. M. G.
Published: February 2010

Background

A disintegrin and metalloprotease 12s (ADAM12s) is a potential first trimester serum marker for fetal trisomy and adverse pregnancy outcome in singletons. In this study, ADAM12s levels in first trimester serum of uncomplicated and complicated twins were evaluated.

Methods

ADAM12s was studied in maternal serum of 215 twin pregnancies, collected between 2004 and 2008. ADAM12s was measured ‘blind to outcome’ using AutoDelfia (PerkinElmer, Turku, Finland). As a reference, data from 2423 singletons were used.

Results

The median ADAM12s level was increased in euploid twins [1.61 multiples of the median (MoM); n = 209] compared with singletons. The median ADAM12s MoM was significantly lower in monochorionic (1.36 MoM; n = 41) compared with dichorionic twins (1.67 MoM; n = 168) (Mann‐Whitney U test, p = 0.005). Trisomy 21 was identified in two pregnancies. Median ADAM12s MoM in twins complicated by hypertensive disorders (1.77 MoM, n = 35) or small for gestational age fetus (1.54 MoM; n = 24) was not significantly different from uncomplicated twins (1.64 MoM; n = 134).

Conclusion

Median ADAM12s MoM in euploid twins was increased compared with singletons. Monochorionic had significantly lower median ADAM12s MoM than dichorionic twins. Median ADAM12s MoMs were not significantly different in twins complicated by hypertensive disorders or small for gestational age fetus compared with uncomplicated twins. Copyright © 2010 John Wiley & Sons, Ltd.
Resolvent of large random graphs
Authors: Bordenave Charles , Lelarge Marc
Published: February 2010

We analyze the convergence of the spectrum of large random graphs to the spectrum of a limit infinite graph. We apply these results to graphs converging locally to trees and derive a new formula for the Stieltjes transform of the spectral measure of such graphs. We illustrate our results on the uniform regular graphs, Erdös‐Rényi graphs and graphs with a given degree sequence. We give examples of application for weighted graphs, bipartite graphs and the uniform spanning tree of n vertices. © 2010 Wiley Periodicals, Inc. Random Struct. Alg., 2010
A closer look at the internal corrosion test for automotive heat exchangers: the OY water test
Authors: Szala E. , Wainer M. , Vieregge K.
Published: February 2010

Nowadays, automotive heat exchangers are mainly made from aluminum. Over the last few decades, the development of aluminum brazing sheet has been mainly focused on the improvement of the external corrosion resistance. Recently, the interest of the heat exchanger manufacturers has also moved toward the assessment of the internal corrosion resistance. Accelerated tests are used to simulate in‐service conditions. These tests are crucial as they provide information to predict the material and product performance. Various internal corrosion tests have been developed, the so‐called ‘OY water tests’. Among all companies, the testing parameters can be varied in terms of ion concentrations or pH. Although the OY water tests are constantly being improved, there is so far no common internal corrosion standard as existing for external corrosion assessment. The present work aims at providing better understanding corrosion mechanisms encountered in the OY water media. The role of various elements present in the solution, cupric, chloride, sulfate ions, has been determined. These parameters were assessed via immersion testing. In order to get better understanding of the corrosion mechanism, electrochemical analysis combined with SEM characterization was carried out. The electrochemical analysis enables the understanding of the thermodynamics and kinetics of the corrosion process while immersion tests are performed to quantify the level of corrosion and follow the surface evolution over time. Copyright © 2010 John Wiley & Sons, Ltd.
Apatite–nanodiamond composite as a functional coating of stainless steel
Authors: Pecheva E. , Pramatarova L. , Hikov T. , Fingarova D. , Tanaka Y. , Sakamoto H. , Doi H. , Tsutsumi Y. , Hanawa T.
Published: February 2010

Biological apatite (AP) is the main component of human bones, and it is a highly bioactive and biocompatible inorganic material. However, it has insufficient mechanical parameters and adhesion to surfaces. Carbon‐based coatings, such as diamond‐like carbon, carbon nanotubes and amorphous carbon are found to significantly improve the mechanical properties of AP, increase its adhesion, prevent metal ion release from metal implants and inhibit the formation of fibrous tissue and blood clotting upon implantation.

In this study, nanodiamond (ND)‐reinforced AP composite coating was prepared by electrodeposition on austenitic stainless steel from simulated body fluid (SBF) containing ND particles. Results revealed the formation of dense and homogeneous AP coating, containing CO3 and HPO4 groups similar to the biological AP. The composite coating was characterized by ductility, improved hardness and adhesion to the steel surface in comparison to pure AP. Mineralization experiment in a simulated body fluid revealed that the composite coating is potentially biologically active. Copyright © 2010 John Wiley & Sons, Ltd.
Blessures dans la filiation et infertilité masculine : étude comparative et psychodynamique
Authors: Jaoul M. , Albert M. , Bailly M. , Selva J. , Molina Gomes D.
Published: February 2010

Cette recherche est née de la constatation clinique, à travers les récits de vie d’hommes infertiles, de l’existence de perturbations dans leur filiation. Dans un premier temps, il s’agira de déterminer, à l’aide d’une grille de filiation construite à partir d’une clinique psychanalytique, si, pour certains de ces hommes infertiles, le projet de devenir père pourrait être entravé par leur difficulté à se situer dans leur généalogie et à s’identifier à leur propre père. La comparaison d’un groupe de 30 hommes infertiles avec un groupe de 30 hommes fertiles permet de mettre en évidence l’impact de certains événements dans la filiation sur la capacité à procréer. Le second temps de la recherche sera consacré à une approche psychodynamique qui tentera d’éclairer l’hypothèse d’un lien entre l’impact traumatique de ces événements sur les sujets et sa traduction dans une expression somatique.
Le deuil de la fertilité dans l’insémination avec sperme de donneur (IAD)
Authors: Mazzone J.-C.
Published: February 2010

La pratique de l’IAD suscite paradoxalement chez l’homme stérile un blocage du deuil de sa fertilité. La mise en secret de la conception de l’enfant en est le symptôme. L’aide psychologique nécessaire à l’élaboration du deuil permettra la levée de ce secret, mais cela n’est pas suffisant pour l’accès de cet homme à la paternité. Il devra, en se reconnaissant actif et concepteur de son enfant, s’affronter à l’homosexualité latente inhérente à la pratique de l’IAD. Le travail de deuil mené à son terme verra l’homme stérile devenir un père authentique et serein.
A Review and Illustration of Contemporary Percutaneous Nephrolithotomy Practice Using Intracorporeal Techniques through Single Punctures for Complex Stone Burden in a UK Tertiary Referral Centre
Authors: Heer Rakesh , Veeratterapillay Rajan , Haslam Philip , Hasan S. Tahseen
Published: February 2010

Objective:

The treatment of complex renal stones remains challenging for surgeons using percutaneous nephrolithotomy (PCNL). A number of contemporary accessory techniques can help improve stone clearance allowing a reduction of multiple punctures and morbidity. We report our experience using a single puncture for complex stone cases.

Patients and methods:

We reviewed the practice of single puncture for complex stones (partial staghorns involving multiple calyces and complete staghorns) in our Institute from 2004 to 2007. These cases included paediatric patients who would otherwise typically endure open nephrolithotomy. Stone clearance, by intra-operative renoscopy and post-operative KUB, and requirement for ancillary procedures was assessed.

Results:

In total 35 complex stone cases were identified that matched the inclusion criteria (4 children). All patients were treated with a solitary puncture and two cases were abandoned due to excessive bleeding at the time of percutaneous access. Of the 33/35 cases that progressed fluoroscopic stone clearance was achieved. Case-based illustrations are presented showing accessory techniques such as intracorporeal catheters, flexible cystoscopy, basketing, lasering and percutaneous needle manipulations that facilitated these results.

Conclusions:

In cases of complex renal stone disease, the use of contemporary PCNL techniques can allow significant stone clearance through a single puncture in most cases. A team approach with intervention radiologists is emphasized.
Ceramide‐rich platforms in transmembrane signaling
Authors: Stancevic Branka , Kolesnick Richard
Published: February 2010

Recent evidence suggests that ceramide regulates stress signaling via reorganization of the plasma membrane. The focus of this review will be to discuss the mechanism by which acid sphingomyelinase (ASMase)‐generated ceramide initiates transmembrane signaling in the plasma membrane exoplasmic leaflet. In particular, we review the unique biophysical properties of ceramide that render it proficient in formation of signaling domains termed ceramide‐rich platforms (CRPs), and the role of CRPs in the pathophysiology of various diseases. The biomedical significance of CRPs makes these structures an attractive therapeutic target.