#A3937, Sigma) at 2000 times dilution with immunoreaction enhance

#A3937, Sigma) at 2000 times dilution with immunoreaction enhancer (Can Get Signal® Solution 2, TOYOBO Co. Ltd.,

Osaka, Japan) for 1 hour at room temperature. After washing with TBS-T, signals were generated by overlaying the membrane with ECFTM substrate (GE Healthcare, Piscataway, NJ, USA) for 5 min at room temperature under dark conditions. The Attophos (Ex; 440nm, Em; 560nm) was detected by Molecular Imager Fx (Bio-Rad, Hercules, CA, USA). The densitometry of western blots was carried out by using Image J software (National Institutes of Health, Bethesda, MD, USA). Statistical analysis Normalized relative expression of each control data (showed PF-6463922 mw as the ratio to β-actin mRNA expression) was transferred to a normal distribution with a mean of 1.0. In order to normalize the control data, they were fitted by using the SNX-5422 research buy following function: Z(xi): all adjusted data; xi: ith experimental data, x(control): a mean of repeated control data; and σx was a standard deviation of repeated control or trial data. Similarly, normalized relative expression for heat-stable ETEC PAMPs and lactobacilli data was fitted to this function to show them as a fold value compared to the control data. Each of data number repeated in a same condition was from 8 to 10. Statistical analysis was performed by using SAS computer program, ver.6.0 and GLM procedure.

The multiple comparisons among means of fold expression were carried out by Fisher’s LEE011 mouse least significance differential test, LSD method. Differences were significant at 5% level and were showed in graphs with superscripts letters (for differences between means) or asterisks (for differences between each treatment a control). Results Expression of TLRs in BIE cells In order to study the mechanisms by which bovine IECs induce immune responses against intestinal

pathogens, we have previously established a clonal bovine intestinal epithelial cell line (BIE cells). When BIE cells are cultured they assume monolayer cobblestone and epithelial-like morphology with close contact between the cells [17]. Moreover, scanning electron microscopy examination of BIE cell reveled that 3-days old cells have irregular and slender microvilli-like structures on their surface and that this structures increase Abiraterone research buy in complexity as the cells grow [17]. In this work, we applied real-time quantitaive PCR to analyze the expression of TLRs mRNA in BIE cells. All TLRs genes were expressed in BIE cells (Figure 1A). Among TLR family, TLR1, 3, 4 and 6 were strongly expressed, followed by TLR5, 8, 9, 10, 2 and 7. We were particularly interested in expression of TLR2 and TLR4 as the main receptors detecting LAB and ETEC respectively. Therefore, to confirm these real-time PCR findings, we further examined the expression of TLR2 and 4 proteins in BIE cells using anti-TLRs antibodies that are able to cross-react with bovine TLRs (Figure 1B).

Journal of Exercise Physiology online 2003,6(4):16–22 84 Greenw

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Stout JR, Kerksick CM: Putting to rest the myth of creatine supplementation leading to muscle cramps and dehydration. Br J Sports Med 2008,42(7):567–73.PubMedCrossRef 87. Buford TW, Kreider RB, Stout JR, Greenwood M, Campbell B, Spano M, Ziegenfuss T, Lopez H, Landis J, Antonio J: International Society of Sports Nutrition position stand: creatine supplementation and exercise. J Int Soc Sports Nutr 2007, 4:6.PubMedCrossRef 88. Brown EC, DiSilvestro SGC-CBP30 mw RA, Babaknia A, Devor ST: Soy versus whey protein bars: effects on exercise training impact on lean body mass and antioxidant status. Nutr J 2004, 3:22.PubMedCrossRef 89. Candow DG, Burke NC, Smith-Palmer T, Burke DG: Effect of whey and soy protein supplementation combined with resistance training in young adults. Int J Sport Nutr Exerc Metab 2006,16(3):233–44.PubMed 90. Flakoll PJ, Judy T, Flinn K, Carr C, Flinn S:

Postexercise protein supplementation improves health and muscle soreness during basic military training in Marine recruits. J Appl Physiol 2004,96(3):951–6.PubMedCrossRef

91. Kalman D, Feldman S, Martinez M, Krieger DR, Tallon MJ: Effect of protein source and resistance training on body composition and sex hormones. J Int Soc Sports Nutr 2007, 4:4.PubMedCrossRef 92. Biolo G, Williams BD, Fleming RY, Wolfe RR: Insulin action on muscle protein kinetics mafosfamide and amino acid transport during recovery after resistance exercise. Diabetes 1999,48(5):949–57.PubMedCrossRef 93. Borsheim E, Tipton KD, Wolf SE, Wolfe RR: Essential amino acids and muscle protein recovery from resistance exercise. Am J Physiol Endocrinol Metab 2002,283(4):E648–57.PubMed 94. Burk A, Timpmann S, Medijainen L, Vahi M, Oopik V: Time-divided ingestion pattern of casein-based protein supplement stimulates an increase in fat-free body mass during resistance training in young untrained men. Nutr Res 2009,29(6):405–13.PubMedCrossRef 95. Cribb PJ, Williams AD, Carey MF, Hayes A: The effect of whey isolate and resistance training on strength, body composition, and plasma glutamine. Int J Sport Nutr Exerc Metab 2006,16(5):494–509.PubMed 96. Hoffman JR, Ratamess NA, Tranchina CP, Rashti SL, Kang J, Faigenbaum AD: Effect of protein-supplement timing on strength, power, and body-composition changes in resistance-trained men. Int J Sport Nutr Exerc Metab 2009,19(2):172–85.PubMed 97.

Psychol Med 32:333–345CrossRef Chandola T, Martikainen P, Bartley

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Your comprehensive knowledge of this research field has been bala

Your comprehensive knowledge of this research field has been balanced by an all-embracing intimacy with the rich spectrum of personalities within. Without your initiative and great effort their personal perspectives had hardly been told. We owe you a lot! Please, accept “meine herzlichen Glückwünsche zu Deinem 80-sten Geburtstag”, and my admiration for your rich life! [Govindjee’s association with Wolfgang Junge goes back many years into the 1970s. With his PhD student Rita Khanna, Govindjee went to Junge’s lab in Berlin and they

provided AR-13324 cell line the very first measurement showing involvement of bicarbonate in proton uptake and release (see Khanna et al. 1980). Several black and white photographs of Junge appear in a historical article Govindjee wrote (Govindjee and Yoo 2007)… JJE-R.] Nancy Kiang National Aeronautics and Space Administration (NASA) Goddard Institute for Space Studies New York, NY As a young postdoc exploring outside my field of PD-1/PD-L1 inhibitor biometeorology, with burning curiosity about the reason for the vegetation “red-edge,” and with no one to speak to about this, I came across an old textbook figure of absorbance spectra of photosynthetic pigments. The credit was [given to] Govindjee, so I desperately

tracked him down. That happy contact led to my introduction to the wonderful community of photosynthesis Temozolomide nmr researchers, whose characteristic collegial and nurturing interactions surely are so because of Govindjee’s warm and enthusiastic influence. Govindjee and I eventually updated that early figure, and co-authored two very well received papers (Kiang et al. 2007a, b), which further led to a Scientific American

article and now an on-line database of biological pigment spectra. I am happy to add walking the Great Wall 2 of China with Govindjee to my list of milestones. Thanks to Govindjee (see Fig. 4) for getting me on my feet and into the inspiring world of photosynthesis, the science and the people. David Knaff Editor-in-Chief, Photosynthesis Research Professor of Chemistry and Biochemistry Texas Tech University, Lubbock, TX It is a distinct pleasure to contribute a few personal remarks about Govindjee on the occasion of his Tau-protein kinase 80th birthday. When I agreed to become the editor-in-chief of Photosynthesis Research, I did so with considerable trepidation. This was in part because I would be succeeding Bob Blankenship and, given the outstanding job Bob had done during his tenure as editor, I knew that matching his performance would be no small task. On top of that, I could not avoid thinking of the fact that the bar for defining a successful editorship had already been set at a very high level in the earlier time when Govindjee had served as editor of the journal.

Light microscopy showed that culturing with cytokines resulted in

Light microscopy showed that culturing with cytokines resulted in large cells with oval or irregularly shaped nuclei and many small dendrites

(Fig. 2, compare panel B to panel A). Phenotypically, FACS analysis showed that fresh (i.e., uncultured) F4/80-B220-CD11c+ cells expressed moderate levels of CD40; low levels of Ia, CD80, CD86, and DEC-205 molecules; and were negative for F4/80 and CD8α antigen (Fig. 3). selleck Functionally, these cells were unable to stimulate allogeneic T cells in a MLR assay (Fig. 4). By contrast, cultured F4/80-B220-CD11c+ cells expressed high levels of Ia, CD86, CD80, and DEC-205 antigen (Fig. 3) and acquired the capacity to enhance allogeneic T cell proliferation INCB28060 datasheet as effectively as mature, BM-derived DCs (Fig. 4). Figure 2 Morphological characteristics of CCL3 and CCL20-recruited F4/80 – B220 – CD11c + cells before and after culture. (A), Fresh CCL3 and CCL20-recruited F4/80-B220-CD11c+ cells were sorted from PBMNCs of mice by FACS and observed by light microscopy (original magnification ×200). (B), These cells were cultured with GM-CSF and TNFα for 5~6 days, then were observed by light microscopy (Giemsa staining was performed, original

magnification ×400). Figure 3 Immunophenotypic analysis of CCL3 and CCL20-recruited F4/80 – B220 – CD11c + cells. CCL3 and CCL20-recruited F4/80-B220-CD11c+ cells cultured for 5~8 days were incubated with PE or FITC-labeled MAbs. The phenotype of these cells was analyzed by immunofluorescence

staining as described in the SCH727965 manufacturer Materials and Methods. Results are given as means ± SD from three independent experiments. Figure 4 The capacity of CCL3 and CCL20-recruited F4/80 – B220 – CD11c + cells to enhance allogeneic MLR. Allogeneic MLR were performed using splenic T cells purified from B6 mice as responder cells. Fresh and cultured F4/80-B220-CD11c+ 4��8C cells were treated with MMC to arrest cell proliferation and were used as stimulator cells at the indicated cell numbers, respectively. Macrophage were used as controls. T cell proliferation was determined with MTT after 5 days of culture. Results are expressed as the mean ± SD of triplicate cultures. All data are representative of three independent experiments. Generation of tumor-specific CTL induced byDC-Ad-MAGE-1 ex vivo To study the potential of CCL3 and CCL20-recruited DCs in anti-tumor immunity ex vivo, DC-MAGE-1 were employed after five days of culture with GM-CSF and IL-4. Splenic T cells from naïve mice were primed ex vivo with DC-Ad-MAGE-1 in the presence of IL-2 and IL-7 to elicit cytolytic reactivity against tumor cells. When T cells primed with DC-Ad-MAGE-1 were added to tumor cells, they were able to efficiently and specifically lyse MFC, but not B16F10 tumor cells, which do not express MAGE-1. The results also showed that T cells primed with DC-Ad-LacZ or untreated DC did not induce specific CTL (Fig. 5).

841 – 24 494)   Gendera Male

35 median 4 037 0 817 3 200

841 – 24.494)   Gendera Male

35 median 4.037 0.817 3.200 0.247 0.986 0.611 9.794 0.746 12.670 0.379       (range) (0.427 – 61.171)   (0.035 – 17.376)   (0.020 selleck products – 6.229)   (0.000 – 64.312)   (0.100 – 45.381)     Female 5 median 4.331   1.454   1.191   9.102   19.520         (range) (3.223 – 6.581)   (0.677 – 7.218)   (0.562 – 2.361)   (5.989 – 12.900)   (5.367 – 23.448)   T classificationb 1 2 coefficient rs = -0.264 0.114 rs = 0.089 0.583 rs = -0.017 0.919 rs = 0.223 0.170 rs = -0.327 0.041*   2 10                         3 22                         4 6                       LN metastasisa N (-) 15 median 2.399 0.037* 2.926 0.964 0.983 0.800 6.947 0.226 18.801 0.020*       (range) (0.427 – 6.092)   (0.059 – 11.250)   (0.193 – 5.137)   (0.000 – 42.360)   (0.841 – 45.381)     N (+) 25 median 4.443   3.602   1.094   12.037   10.688         (range) (1.379 – 61.171)   (0.035 – 17.376)   (0.020 – 6.229)   (0.936 – 64.312)   (0.100 – 23.697)   Histological gradeb I 21 coefficient rs = 0.155 0.338 rs = 0.462 0.004* rs = 0.374

0.021* rs = 0.381 0.019* rs = -0.026 0.873   II 12                         III 7                       Vascular invasiona Negative 32 median 3.478 0.133 3.393 0.360 1.006 0.608 9.369 0.913 14.999 0.085       (range) (0.640 – 61.171)   (0.035 – 17.376)   (0.020 – 5.538)   (0.000 – 64.312)   (0.100 – 45.381)     ACP-196 supplier Positive 8 median 10.759   2.250   1.264   9.794   7.799         (range) (0.427 – 43.355)   (0.059 Dabrafenib – 6.356) Sucrase   (0.193 – 6.229)   (1.246 – 29.053)   (0.841 – 23.697)   Lymphatic invasiona Negative 22 median 4.037 0.800 3.939 0.195 0.936 0.554 9.027 0.554 15.966 0.192       (range) (0.640 – 61.171)   (0.035 – 11.250)   (0 020 – 5.137)   (0.000 – 64.312)   (1.373 – 38.234)     Positive 18 median 4.733   2.155   1.104   10.915   10.694         (range) (0.427 – 60.921)  

(0.059 – 17.376)   (0.086 – 6.229)   (0.936 – 31.933)   (0.100 – 45.381)   Perineural invasiona Negative 30 median 4.128 0.841 2.212 0.016* 1.006 0.286 7.720 0.008* 14.891 0.617       (range) (0.427 – 61.171)   (0.035 – 11.250)   (0.020 – 5.137)   (0.000 0 64.312)   (0.100 – 38.234)     Positive 10 median 5.247   6.345   1.114   13.886   11.907         (range) (0.640 – 60.921)   (2.250 – 17.376)   (0.458 – 6.229)   (9.027 – 31.933)   (2.089 – 45.381)   aMann-Whithey U test, bSpearman rank correlation coefficient. *Statistically significant. LN = lymph node, rs = correlation coefficient. Univariate and multivariate analyses of risk factors affecting lymph node metastasis To determine the risk factors predictive of lymph node metastasis, we further examined the correlation of lymph node metastasis with other clinicopathological factors. As shown in Table 3, advanced T-classification was significantly correlated with lymph node metastasis (p = 0.036).

D Miller Seattle, WA, USA) Packaging cells were transfected with

D Miller Seattle, WA, USA). Packaging cells were transfected with plasmids pTG 5391 (FB29 LTR-lacZ-SV40-Puro-LTR, clone E17-12 -TG 5391) or pTG 9344 (FB29 LTR-PGK-TK-IRES-Neo -LTR clone E 17-21 pTG 9344) to isolate the retroviral producer clone E17-12 -TG 5391 and E 17-21 TG 9344 (Transgene S.A., Strasbourg, France). PF-02341066 cell line The retroviral producer clone were cultured in DMEM supplemented with 4.5 g/L of glucose, 1% non-essential amino acids, 40 μg/ml gentamycin (Sigma) and 10% calf serum. Culture supernatant was harvested, filtered through a 0.45 μm nitrocellulose filter (Sartorius, Goettingen, Germany) and used in the presence of polybrene (Sigma) at 8 μg/ml final concentration.

NIH 3T3 fibroblasts were cultured in DMEM supplemented with 40 μg/ml gentamycin and 10% heat inactivated NBBS (GIBCO/BRL). Retroviral titration was determined by infecting NIH 3T3 fibroblasts with serial dilutions of the culture medium and staining respectively for β-galactosidase activity with X-gal protocol [26] or for HSV-TK expression using monoclonal antibody anti-HSV-TK as described below. All point titrations were performed four times. The titer of viral preparation was 4.9 (± 1.2) × 106 focus-forming units (FFU/ml) for TG 9344 and 1.7 (± 0.9) × 107 FFU/ml for TG 5391. The absence of competent replication helper retrovirus was checked by NIH 3T3 mobilization assay Treatment of cells with MTX, ara-c or aphidicolin

DHDK12 and HT29 cells were plated into 12 well plates at

5.105 cells/well and treated with SYN-117 mouse 0.08 μM methotrexate Rebamipide (Wyeth-Lederle, Puteaux, France) or 0.075 μM 1-β-D-arabinofuranosyl (Cytarabin-Pharmacia-Upjohn) or 25 μM aphidicolin (Sigma) for 24 hr. The concentrations of the drugs used in our study were chosen according to ABT 888 previously published studies [19, 21, 22]. Furthermore, we determined the IC50 of these drugs by a growth curve analysis. All concentrations used in our study were lower than the calculated IC50 (Table 1). After treatment, the drug-containing medium was removed; the cells were washed twice with phosphate-buffered saline (PBS) and fresh medium was provided. Every 2 to 6 hr during 72 hr, cell cycle distribution were obtained by flow cytometric determination of the DNA content of propidium-iodide (PI)-stained cells as described previously [27]. The cells were analyzed on a cytofluorometer EPICS XL-MCL (Coulter Beckman, Miami, USA) with an argon laser emitting at a wavelength of 488 nm. The analysis of fluorescence was carried out starting from an acquisition window determined by a two dimensional histogram representing the structure of the cells scaled to their size. This acquisition window was then used to produce a histogram representing the number of PI positive cells sorted by intensity of fluorescence, expressed in logarithmic curve mode. Table 1 IC50 of Methotrexate, Ara-C and Aphidicolin in DHDK12 and HT29 cell lines IC 50 Methotrexate Ara-C Aphidicolin DHDK12 cells 0.16 μM 40 μM 30 μM HT29 cells 0.

A remarkable feature of evolution of phylogroup 1 Pav is the extr

A remarkable feature of evolution of phylogroup 1 Pav is the extremely fluid nature of their T3SE repertoires. Like other

phylogroup 1 strains, the frequency of T3SE acquisition is extremely high, with 27 T3SEs acquired since it diverged from the common ancestor of the group. However, the rate of T3SE loss is much higher than has been documented for any other P. syringae strain. A total of twelve Pav BP631 T3SEs are inferred to be non-functional. CP-690550 clinical trial By comparison, the strain with the second most T3SE pseudogenes is Pto DC3000 with seven [16]. All of the pseudogenization events in Pav BP631 appear to have happened since it diverged from Pmp 302280 and Pan 302091. Indeed, seven of them involve T3SEs that were acquired since this divergence, meaning that they were either acquired as nonfunctional genes or that they became pseudogenes after acquisition. The frequency of T3SE gain and loss is much lower in the phylogroup 2 Pav strains, with six and five gains for Pav Ve013 and Pav Ve037 respectively since they diverged from other phylogroup

2 strains. This is typical of the phylogroup as a whole, with three other strains that have acquired six or less T3SEs and the largest number of T3SE gains being twelve in Ppi 1704B. Two of the Pav BP631 T3SE putative pseudogenes, avrE1 and hopM1, are notable because they are located in the CEL, which is present in all P. syringae strains with canonical hrp/hrc type III secretion systems. AvrE1 is essential for virulence in some P. syringae strains [28], but is functionally redundant with HopM1 in Pto DC3000, where it suppresses salicylic acid-mediated CP673451 purchase immunity [29]. Frameshift mutations and truncations are common in hopM1, including in Pph 1448A [8], P. syringae pv.

Selleckchem Staurosporine aptata DSM 50252 [4] and Pto T1 [10]. To date, all sequenced strains have had intact avrE1 genes, except for Psv 3335 [15], which has a contig break in the gene and Por 1_6, which has a premature stop codon, but has an intact hopM1 gene [14]. Homologs of avrE are also present in a number of other plant pathogens, including Erwinia amylovora and Pantoea stewartii, where it is essential for virulence [30–32]. Since P. syringae mutants lacking both of these T3SEs have strongly impaired virulence [33] it is unclear how Pav BP631 is able to establish infection without functional MGCD0103 datasheet copies of either gene. It is possible that HopR1 [34] or another uncharacterized T3SE compensate for the loss of AvrE and HopM1 in hazelnut. Alternatively, a low level of translation might be initiated off the highly-atypical GTA start codon in avrE[23] or another in-frame start codon might be used, though this would be likely to have drastic effects on the N-terminal secretion signal and there are no other obvious candidates for ribosome binding sites. Of the twelve putatively non-functional T3SEs in Pav BP631, four have intact homologs in phylogroup 2 Pav.

Med Care 2007, 45:1195–1204 PubMedCrossRef 59 Meyers FJ, Linder

Med Care 2007, 45:1195–1204.PubMedCrossRef 59. Meyers FJ, Linder J: Simultaneous care: disease treatment and palliative AZD9291 care throughout illness. J Clin Oncol 2003, 21:1412–1415.PubMedCrossRef 60. Lagman R, Walsh D: Integration of palliative medicine into comprehensive cancer care. Semin Oncol 2005, 32:134–138.PubMedCrossRef 61. Malin JL: Bridging the divide: integrating cancer-directed therapy and palliative care. J Clin Oncol 2004, 22:3438–3440.PubMedCrossRef 62. Gelmon SB: Accreditation, core curriculum and allied health education: barriers and opportunities. J Allied Health 1997, 26:119–125.FK866 molecular weight PubMed 63. Insalaco

D, Ozkurt E, Santiago D: Attitudes and knowledge of students in the allied health professions toward their future professional team members. J Allied Health 2006, 35:142–146.PubMed 64. Strohschein this website J, Hagler P, May L: Assessing the

need for change in clinical education practices. Phys Ther 2002, 82:160–172.PubMed Competing interests The authors declare that they have no competing interests. Authors’ contributions MB conceived the paper, interpreted data and wrote the final manuscript; CZ conceived the paper, interpreted data and wrote the final manuscript; AP reviewed and commented the last version of the manuscript; AMDN helped to revise the first draft of the manuscript; MS and GS reviewed and commented the last version of the manuscript; FP interpreted data, reviewed and commented the last version of the manuscript. All authors read and approved the final manuscript.”
“Background The lymphatic system functions in regulating tissue fluid balance and immune cell trafficking, and it is involved in the pathogenesis of edema and metastasis. Tumor cell dissemination to lymph nodes (LNs) through the lymphatic system is common and early event in human malignant tumors. LN metastasis is the first sign of tumor progression in most malignant tumors, and is a crucial determinant in their staging, prognosis,

and treatment [1]. Lymphatic metastasis was considered a passive process, where detached tumor cells entered LNs via pre-existing lymphatic vessels proximate to the primary tumors [2]. Sentinel LNs (SLNs) Obatoclax Mesylate (GX15-070) are defined as the first LNs to receive cells and fluid from primary tumors through lymphatic vessels [3]. Malignant cells at SLNs were believed to then enter the blood stream via high endothelial venules or continue through the lymphatic drainage system, exiting into the blood stream via anastomoses such as the thoracic duct [4]. Changes in LNs begin before metastasis, a process termed tumor-reactive lymphadenopathy [5]. Regional LNs proximate to the primary tumors are commonly enlarged because of reactive lymphadenopathy, tumor metastasis, or both, suggesting that LN alteration results from interactions between tumors and the lymphatic system.

The main reason for the difficulties in demonstrating an impact o

The main reason for the difficulties in demonstrating an impact on fracture incidence in these long-term studies is the

absence of a placebo control. One solution is to compare fracture incidence with the first years of the study, in which selleckchem efficacy versus placebo has already been demonstrated. Thus, the 8-year pooled analysis of SOTI and TROPOS reported no statistical PF-4708671 cell line difference between incidence of fracture in the first 3 years of the trials (years 0 to 3) and the first 3 years of the extension (years 6 to 8) for vertebral, nonvertebral, or any osteoporotic fracture [13]. Our finding of similar rates in the first 5 years (years 0 to 5) and the last 5 years (years 6 to 10) reinforces the conclusion that the antifracture efficacy of strontium ranelate is sustained in the long-term. However, we also compared these cumulative incidences with those in a FRAX®-matched placebo population in the TROPOS study in an exploratory post hoc analysis. The advantage of FRAX® is that it provides estimates of 10-year fracture risk [16, 17], presenting the opportunity to identify patients at the same level of risk at the beginning of a 5-year observation period, as the 10-year population at year 5, reducing confounders such as aging of the population, prevalent fracture, and other risk factors. We used FRAX® scores calculated without BMD in patients already treated with strontium ranelate

for 5 years, precluding GSK1838705A any potential bias related to the effect of treatment on BMD. On the other hand, FRAX® does not account for the number MycoClean Mycoplasma Removal Kit and severity of prevalent fractures, which is a limitation of the tool. Our results of lower rates of fracture in the patients between 5 and 10 years of treatment versus this matched placebo group strongly support sustained long-term

antifracture efficacy of strontium ranelate over 10 years. Our observation of a similar efficacy between 6 and 10 years as in the first 5 years of treatment is also in line with the reported absence of influence of age, baseline BMD, or other risk factors on the efficacy of strontium ranelate [11]. Moreover, a recent analysis by Kanis confirmed that the efficacy of strontium ranelate in clinical and morphometric fracture did not depend on baseline fracture risk assessed by FRAX® [20], whereas the same analyses performed with antiresorptive agents such as denosumab [21] and clodronate [22] indicated efficacy against clinical osteoporotic fracture in patients at moderate and/or high risk only. The levels of compliance with strontium ranelate over 10 years compare well with those reported in the long-term studies with alendronate [2, 23], even considering the design of this extension study, in which the patients themselves chose to continue treatment. Our study has the limitations of many long-term trials in the management of a chronic disease (absence of comparator, small sample size, and open-label design).