Conclusions A delicate balance between innate and adaptive immuni

Conclusions A delicate balance between innate and adaptive immunity is required for efficient functioning of the immune system. This balance is important in cancer immunity, immune response against pathogens, and avoiding hypersensitivity reactions [20]. In this study, we have demonstrated that carbon dots could adjust the immune function of BALB/c mice by inducing Th1 and Tc responses. However, these effects were see more not enough to induce the morphological change of immune organs. The mechanism by which carbon dots modulate the immune system remains unclear. More systematic and profound studies are needed, and the pertinent testing guidelines for immunological evaluation of nanoparticles need to be formulated

quickly. Acknowledgments We are grateful for the financial support from the 973 Program. This work was supported by grants from National Basic Research Program of China (2010CB933904), National Natural Science Foundation of China (31170961,81101169) and Biomedical

and Engineering Multidisciplinary Funding of SJTU no Captisol price YG2012MS13. References 1. Cahalan MD, Parker I, Wei SH, Miller MJ: Two-photon tissue imaging: seeing the immune system in a fresh light. Nat Rev Immunol 2002, 2:872–880. 10.1038/nri935 2749751 12415310CrossRef 2. Helmchen F, Denk W: Deep tissue two-photon microscopy. Nat Methods 2005, 2:932–940. 10.1038/nmeth818 16299478CrossRef 3. Zheng H, Chen G, DeLouise LA, Lou Z: Detection of the cancer marker CD146 expression in melanoma cells with semiconductor quantum dot label. J Biomed Nanotechnol 2010, 6:303–311. 10.1166/jbn.2010.1136 21323102CrossRef 4. Zhang X, Li D, Wang C, Zhi X, Zhang C, Wang K, Cui D: A CCD-based reader combined quantum dots-labeled lateral flow strips for ultrasensitive quantitative detection of anti-HBs antibody. J Biomed Nanotechnol 2012, 8:372–379. 10.1166/jbn.2012.1401 22764406CrossRef 5. Zhao L, Caot JT, Wu ZQ, Li JX, Zhu JJ: Lab-on-a-Chip for anticancer drug screening using quantum dots probe based apoptosis assay. J Biomed Nanotechnol 2013, 9:348–356. 10.1166/jbn.2013.1546

Amisulpride 23620989CrossRef 6. Chan WC, Nie S: Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 1998, 281:2016–2018. 9748158CrossRef 7. Hardman R: A toxicologic selleck chemicals llc review of quantum dots: toxicity depends on physicochemical and environmental factors. Environ Health Perspectives 2006, 114:165–172. 10.1289/ehp.8284CrossRef 8. Sun YP, Zhou B, Lin Y, Wang W, Fernando KA, Pathak P, Meziani MJ, Harruff BA, Wang X, Wang H, Luo PG, Yang H, Kose ME, Chen B, Veca LM, Xie SY: Quantum-sized carbon dots for bright and colorful photoluminescence. J Am Chem Soc 2006, 128:7756–7757. 10.1021/ja062677d 16771487CrossRef 9. Cao L, Wang X, Meziani MJ, Lu F, Wang H, Luo PG, Lin Y, Harruff BA, Veca LM, Murray D, Xie SY, Sun YP: Carbon dots for multiphoton bioimaging. J Am Chem Soc 2007, 129:11318–11319. 10.1021/ja073527l 2691414 17722926CrossRef 10.

These differences suggest that master’s and bachelor’s programs m

These differences suggest that master’s and bachelor’s programs may be, in general, approaching sustainability from fundamentally different perspectives. Less than a quarter of core sustainability courses check details shared any PARP inhibitor one text in their reading material, suggesting that there is currently no widely agreed upon

foundational literature for teaching sustainability. In particular, it is striking that, of the most widely used texts (Table 3), several are more than 40 years old, and only two include the word “sustainable” or “sustainability” in their titles (although four of the eight texts include “resilience”). Further, none of the more recent literature widely cited within the scholarly field of sustainability (e.g., Kates et al. 2001; Clark and Dickson 2003) is currently being widely used in teaching sustainability. This divergence between the scholarly literature Q-VD-Oph supplier and the texts being used in educational programs shows that the field is taking a diverse set of content and institutional approaches under the heading of sustainability. While this may benefit the creativity of the

field, there may be a useful role for a foundational text for education in sustainability to ensure some coherence between programs. One option is presented by the reading lists supplied in the Ruffolo Curriciulum on Sustainability Science (Andersson et al. 2008). Disciplinary vs. interdisciplinary content Overall, courses within the applied sustainability, applied work, and research categories are more prevalent in master’s programs than in bachelor’s programs, which contain more disciplinary courses in the natural sciences, and arts and humanities (Fig. 4). This disparity may explain the lack of stand-alone courses in natural sciences, arts and humanities, and critical social sciences at the master’s level, with these approaches being covered

in these interdisciplinary, more generalist courses. Moreover, it raises the question of how best to integrate the diverse fields that contribute to sustainability education. The approach in master’s programs appears to favor the integration of disciplines in interdisciplinary and applied or research courses, while bachelor’s programs service Dehydratase the interdisciplinary nature of sustainability through existing disciplinary courses. Though the varying approaches taken may reflect the nature of these degrees in general, in both instances it must also be appropriate to the specific requirements of sustainability education. It remains unclear whether discipline-based bachelor’s programs can adequately meet the requirements of sustainability education. More broadly, this analysis raises the question as to what is the appropriate approach to disciplinary content.

Overall, severe

Overall, severe trauma affected adults: 4206 cases in age 0–45, 7495 cases after 45 years. MG-132 Mortality increased with age, reaching nearly 50% in trauma victims older than 75 years. Similarly, hospital and ICU-LOS, rate of admission to ICU and reimbursed DRG, all increased with age, with the higher levels in ages between 13 and 74 years. On the contrary,

pediatric cases (age group 0–12) were CBL-0137 supplier only 482 in three years, with shorter ICU LOS, decreased mortality and lower levels of reimbursement. All of these differences were statistically significant (p < .0001, ANOVA). Table 2 Severe trauma hospitalized in Lombardia according age groups

  Modality of trauma: absolute values Age groups Number Deceased %_ deceased LOS (±SD) % ICU adm ICU LOS (±SD) Avg remb (€) (±SD) 00-06 322 15 4.65 10.65 (15.22) 79.165 3.36 (7.49) 6˙588.98 (11828.14) 07-12 160 4 2.50 12.50 (12.74) 88.75 3.88 (7.81) 7˙492.89 (10229.22) 13-17 411 19 4.62 17.20 (15.94) 95.38 6.39 (9.20) 12˙908.43 (16509.47) 18-45 3313 334 10.08 20.88 (21.35) GSK690693 mouse 93.96 7.66 (11.25) 16˙144.73 (19550.47) 46-64 2148 356 16.57 21.01 (22.31) 85.52 7.57 (12.74) 16˙207.54 (21784.13) 65-74 1657 407 24.56 20.39 (21.06) 74.83 7.13 (11.93) 16˙224.24 (21679.17) >74 3690 1693 45.88 15.21 (16.34) 45.85 3.74 (9.20) 10˙067.29 (16701.65) All differences significant (p < .0001) at D-malate dehydrogenase ANOVA. In

three cases age informations have been missed. The cause of accident has been indicated in 72.98% of cases (Tables 3 and 4) and “other mechanism”, road-related trauma, injured in domestic pertinences and at workplace were the principal conditions. As expected, accidents on the road and at the workplace were the principal causes of trauma for males aging from 18 to 64 years. On the contrary, accidents in domestic pertinences increased with age, being the principal cause of trauma after 64 years, and old women were affected the most. Violence inflicted by others (assault) or self-inflicted violence was rare in Lombardia and affected people 18 to 64 years old. In pediatric age most of cases were domestic or road-related. Statistic analysis demonstrated a significant association at chi-square test between gender and modality of trauma: males had more occupational injuries, trauma on the road and injuries caused by violence by others, while females were more subjected to domestic injuries and self inflicted violence.

tigurinus In total, 20 out of 51 individuals had nicotine consump

tigurinus In total, 20 out of 51 individuals had nicotine consumption, of which 11 had S. tigurinus detected in at least the saliva and/or plaque samples. This was not significant compared to individuals without nicotine consumption (31 out of 51, 16 with S. tigurinus detected in the oral samples), P = 0.813. In the periodontitis group, the number of patients with nicotine consumption and S. tigurinus detected in the oral samples

(n = 7) did not differ significantly from the patients without Ferrostatin-1 nicotine consumption and S. tigurinus in the mouth (n = 6), P = 0.543, respectively. Similar results were observed in the non-periodontitis control group, 4 individuals with nicotine consumption and S. tigurinus detected in the oral DNA Damage inhibitor samples were identified compared to 10 individuals without nicotine consumption but S. tigurinus detected in the mouth, P = 0.793. Discussion Members of the microbial flora originating from the oral cavity may be involved in the pathogenesis of systemic infections [18]. Biofilm formation, complex mechanisms with other bacteria or underlying

diseases might play a crucial role in the development of invasive infections. Regarding the pathogenesis selleck kinase inhibitor of chronic periodontal diseases, complex host-bacterial interactions are responsible for the initiation of tissue destruction [19,20]. Earlier studies have demonstrated that S. mitis, which is the closest related species to S. tigurinus, is a predominant early colonizing species of dental biofilms [21]. Although S. mitis is not a potent

N-acetylglucosamine-1-phosphate transferase inducer of immune responses, it can antagonize the capacity of A. actinomycetemcomitans to stimulate IL-8 [22]. Interaction of S. tigurinus with A. actinomycetemcomitans (a key pathogen associated with aggressive form of periodontitis in younger individuals) might be of interest [23]. Since its recent identification [11,12], it is not clear whether modifying factors are associated with the presence of S. tigurinus in the human oral microbiome and if its detection in the oral cavity has direct clinical implications in systemic diseases. Our data shows that S. tigurinus is a frequent bacterium colonizing the human oral cavity in periodontal health and disease.

The data retention of approximately 103 s is also

The data buy Epacadostat retention of approximately 103 s is also observed under a low operation current of 1 nA (Figure  9b). The resistance ratio is approximately 102. Further study is needed to improve the cross-point resistive switching memory characteristics under low-current operation. In addition, the read pulse endurances of LRS and HRS are more than 105 cycles with a large resistance ratio of >104, and both resistance states are very stable without significant resistance variation for a retention test of more than 104 s under a CC of 50 μA (not shown here), which can be applicable for future low-power high-density nonvolatile memory applications. Figure 9 Switching cycles and data retention. (a) Repeatable

switching cycles and (b) data retention of the Cu/GeO x /W cross-point memory devices under a low CC of 1 nA. Conclusions Resistive switching memory

characteristics using Cu and Al TEs on the GeO GDC-0994 x /W cross-point memory devices have been compared. Improved memory characteristics of the Cu/GeO x /W structures under low current varying from 1 nA to 50 μA and a low voltage operation of ±2 V are observed MI-503 supplier as compared to those of the Al/GeO x /W structures. These cross-point memory structures are observed by HRTEM. The formation of AlO x layer with a thickness of approximately 5 nm at the Al/GeO x interface is observed, which is unstable to control the resistive switching phenomena. The RESET current scalability is observed for Cu TE, while it is high (>1 mA) and independent for the Al TE with CCs varying from

1 nA to 500 μA. Superior resistive switching memory performances in terms of high resistance ratio (102 to 104 under bipolar and approximately 108 under unipolar modes), long pulse endurance of >105 cycles under a CC of 50 μA, and good scalability potential are observed for the Cu/GeO x /W cross-point memory devices. Repeatable switching cycles and data retention of 103 s are also observed under a low CC of 1 nA. This study is important for high-density low-power 3D architecture in the future. Acknowledgements This work was supported by the National Science Council (NSC), Taiwan, under contract numbers NSC-101-2221-E-182-061 and NSC-102-2221-E-182-057-MY2. References 1. Sawa A: Resistive switching in transition metal oxides. Mater Today Resveratrol 2008, 11:28.CrossRef 2. Kim DC, Seo S, Ahn SE, Suh DS, Lee MJ, Park BH, Yoo IK, Baek IG, Kim HJ, Yim EK, Lee JE, Park SO, Kim HS, Chung UI, Moon JT, Ryu BI: Electrical observations of filamentary conductions for the resistive memory switching in NiO films. Appl Phys Lett 2006, 88:202102.CrossRef 3. Waser R, Aono M: Nanoionics-based resistive switching memories. Nat Mater 2007, 6:833.CrossRef 4. Sun X, Li G, Chen L, Shi Z, Zhang W: Bipolar resistance switching characteristics with opposite polarity of Au/SrTiO 3 /Ti memory cells. Nanoscale Res Lett 2011, 6:599.CrossRef 5.

Particle size was evaluated by intensity distribution Atomic for

Particle size was evaluated by intensity distribution. Atomic force microscopy (AFM) study was performed on a Nanoscope Multimode atomic force microscope (Veeco Instruments Inc., New York, USA). Transmission electron microscopy (TEM) image was obtained on a JEM 2100 transmission electron microscope (JEOL, Tokyo, Japan). The amount of drug in the supernatant was assayed using a high-performance

liquid chromatography (Waters Associates, Milford, MA, USA) system with the following conditions: stationary phase, Hypersill ODS column (250 mm × 4.6 mm, 5 μm); Selleck Sapitinib mobile phase, potassium dihydrogen phosphate buffer (pH 4.5)-acetonitrile (88:12); elution flow rate, 1 mL/min; and detection wavelength, 303 nm. The drug-loading content was calculated according to the previous report [12]. In vitro stability tests PBS stability test against ionic strength and plasma SC79 stability test against protein adsorption were evaluated immediately after preparation and subsequently at regular intervals. Briefly, 5 mg of the lyophilized (MTX + PEG)-CS-NPs were suspended in PBS (pH 7.4) or 10% selleck (v/v) plasma/heparin in PBS and stored at 37°C for 120 h. The particle size was determined at 0, 24, 48, 72, 96, and 120 h, respectively. In vitro drug release In vitro release of MTX from the (MTX + PEG)-CS-NPs

was evaluated by a dialysis method. The lyophilized (MTX + PEG)-CS-NPs suspended in 10% plasma (with or without isothipendyl the presence of crude proteases) were added into a dialysis bag (Mw = 6,000 to 8,000 Da) and immersed into the release medium at 37°C with agitation. At the predesigned time points, 2 mL of the release medium was completely withdrawn and subsequently replaced with the same volume of fresh PBS. For comparison, in vitro release of the free MTX was evaluated as a control. Cell culture HeLa cells were cultured in FA-deficient Dulbecco’s Modified Eagle’s Medium

(DMEM) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin. MC 3 T3-E1 cells were cultured in Minimum Essential Medium, Alpha Modified (α-MEM), under similar conditions. The two cell lines have different levels of FA receptor expression. In particular, HeLa cells (cancer cells) are FA receptor positive, and MC 3 T3-E1 cells (normal cells) are FA receptor negative. All of the cells were cultivated in a 5% CO2-humidified atmosphere at 37°C. In vitro cellular uptake To qualitatively investigate the cellular uptake of the PEG-CS-NPs, (FA + PEG)-CS-NPs or (MTX + PEG)-CS-NPs, fluorescein isothiocyanate (FITC) was conjugated to different formulations to prepare the FITC-PEG-CS-NPs, FITC-(FA + PEG)-CS-NPs or FITC-(MTX + PEG)-CS-NPs. HeLa cells were seeded at a density of 8 × 104 cells per well into 6-well plates with their specific cell culture medium. The cells were incubated at 37°C and 5% CO2 for 24 h.

Most importantly, inclusion of epitopes that are immuno-responsiv

Most importantly, inclusion of epitopes that are immuno-responsive

to different arms of the host immune machinery, such as CTL and Th epitope combinations can enable stronger and more efficient immune responses, similar to responses achieved with adjuvant therapies (e.g., [45, 48, 49, 103]). Thus, our study provides a unique strategy to identify suitable epitope candidates for multi-gene/multi-type vaccines that are both highly conserved across the global HIV-1 population and highly likely to co-occur together in the same viral genome in various click here HIV-1 subtypes and thus can be simultaneously targeted by multi-epitope vaccines. Some of these conserved epitopes have been included in Pictilisib in vitro several recently tested vaccine candidates that showed promising results; however, none have included associated epitopes from all three genes. For example, segments of Gag, Pol and Nef were included in the recent LIPO-5 lipopeptide vaccine trial that see more showed T-cell responses

in ~50% of vaccines [104], yet it lacked associated epitopes from Pol (Additional file 11). Further, because the included epitopes are already derived from the lists of epitopes with experimentally demonstrated immunogenicity in humans, (e.g., the list of “”best defined”" CTL epitopes by Frahm et al., 2007 [56]), many challenges associated with the accuracy of computational epitope prediction (e.g., [87, 105, 106]) can be avoided. Moreover, while sequence conservation does not assure that the epitope will be strongly immunogenic (e.g., [107, 108]), associated epitopes reported in this study also exhibit a high degree of nucleotide sequence conservation which is not readily identifiable Thymidylate synthase by other tools, such as Epitope

Conservancy Analysis Tool [107], making them suitable targets for other types of treatments such as RNA interference [109]. Notably, a high degree of amino acid sequence conservation is not the only factor that influences identification of epitopes as promising candidates. For example, several epitopes included in the association rule mining, namely, PIPIHYCAPA (Ab, Env), WASRELERF (CTL, Gag) and RKAKIIRDY (CTL, Pol), were not involved in any of the 60626 associations that we discovered, showing that high conservation at the amino acid level does not automatically translate into involvement in association rules and that other factors are also at play.

PubMedCrossRef 7 Sawers RG: Expression of fnr is constrained by

PubMedCrossRef 7. Sawers RG: Expression of fnr is constrained by an upstream IS5 insertion in certain Escherichia coli K-12 strains. J Bacteriol 2005, 187:2609–2617.PubMedCrossRef 8. Lintner RE, Mishra PK, Srivastava P, Martinez-Vaz BM, Khodursky AB, Blumenthal RM: Limited functional conservation of a global regulator among related bacterial genera: Lrp in Escherichia, Proteus and Vibrio . BMC Microbiol 2008, 8:60.PubMedCrossRef 9. Gentry DR, Hernandez VJ, Nguyen LH, Jensen DB, Cashel M: Synthesis of Selleck CFTRinh-172 the stationary-phase sigma factor sigma S is positively regulated by ppGpp. J Bacteriol 1993, 175:7982–9.PubMed

10. Jishage M, Kvint K, Shingler V, Nyström T: Regulation of sigma factor competition by the alarmone ppGpp. Genes Dev 2002, 16:1260–1270.PubMedCrossRef 11. Ferenci T: Maintaining a healthy SPANC balance through regulatory and mutational adaptation. Mol Microbiol 2005, 57:1–8.PubMedCrossRef 12. Typas A, Becker G, Idasanutlin datasheet Hengge R: The molecular basis of selective promoter activation by the sigmaS subunit of RNA polymerase. Mol Microbiol 2007, 63:1296–1306.PubMedCrossRef 13. Storz G, Hengge-Aronis

R: Bacterial stress responses. ASM Press; 2000. 14. Weber H, Polen T, Heuveling J, Wendisch VF, Hengge R: Genome-wide analysis of the general stress response network in Escherichia coli : sigmaS-dependent genes, promoters, and sigma factor selectivity. J Bacteriol 2005, 187:1591–1603.PubMedCrossRef 15. Potrykus K, Cashel M: (p)ppGpp: still magical? Annu Rev Microbiol 2008, 62:35–51.PubMedCrossRef 16. Cashel M, Gallant J: Two compounds implicated in the function of the BAY 63-2521 price RC gene

of Escherichia Dichloromethane dehalogenase coli . Nature 1969, 221:838–841.PubMedCrossRef 17. Lazzarini RA, Cashel M, Gallant J: On the regulation of guanosine tetraphosphate levels in stringent and relaxed strains of Escherichia coli . J Biol Chem 1971, 246:4381–4385.PubMed 18. Spira B, Silberstein N, Yagil E: Guanosine 3′,5′-bispyrophosphate (ppGpp) synthesis in cells of Escherichia coli starved for Pi. J Bacteriol 1995, 177:4053–8.PubMed 19. Bougdour A, Gottesman S: ppGpp regulation of RpoS degradation via anti-adaptor protein IraP. Proc Natl Acad Sci USA 2007, 104:12896–12901.PubMedCrossRef 20. Cashel M, Gentry DM, Hernandez VJ, Vinella D: The stringent response. In Escherichia coli and Salmonella: cellular and molecular biology. Volume 1. Edited by: Neidhart FC (Ed. in Chief). American Society for Microbiology Washington, D.C; 1996:1458–1496. 21. Spira B, Hu X, Ferenci T: Strain variation in ppGpp concentration and RpoS levels in laboratory strains of Escherichia coli K-12. Microbiology 2008, 154:2887–95.PubMedCrossRef 22. Kvint K, Farewell A, Nyström T: RpoS-dependent promoters require guanosine tetraphosphate for induction even in the presence of high levels of sigma(S). J Biol Chem 2000, 275:14795–14798.PubMedCrossRef 23. Nyström T: Growth versus maintenance: a trade-off dictated by RNA polymerase availability and sigma factor competition? Mol Microbiol 2004, 54:855–862.PubMedCrossRef 24.

Patrick DL, Burke LB, Gwaltney CJ, Leidy NK, Martin ML, Molsen E,

Patrick DL, Burke LB, Gwaltney CJ, Leidy NK, Martin ML, Molsen E, Ring L (2011) Content validity—establishing and reporting the evidence in newly

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“Introduction Teeth and bones are regarded the most mineralized tissues in humans. Several reports suggest association between tooth loss or small number of remaining teeth and reduced bone mineral density (BMD) [1–5]. There is also evidence of the effect of periodontal disease and osteoporosis in the elderly [6–11]. Furthermore, periodontal Navitoclax concentration disease has also been reported an important and common coincidence of systemic bone loss in both women and men [12–16]. It has been shown that the reduction of systemic BMD may be a risk factor for the development of tooth loss and oral health problems [2, 7, 17] suggesting possible cause–effect link, particularly in postmenopausal women with osteoporosis [13, 18, 19]. Some studies also show that dental status impairment related to osteoporosis may

result from a considerable decrease of mandibular bone mass [20, 21], though the contributing factors remain unclear. Possible mechanisms may include tooth loss during ageing as a natural process secondary to the systemic bone loss; however, the age-related progressive dental decline may AMP deaminase also co-exist with deficits in BMD [17, 21]. These associations are well recognized among the elderly but there are still limited data on such associations in younger age. Accelerated tooth wear appears one of the conditions affecting enamel, independently of age, so that it may occur in younger otherwise healthy people. It is well known that tooth enamel is the hardest tissue in the human body. Although enamel does not have the typical find more structure of human bone, its chemical composition is similar. Hydroxyapatite and magnesium phosphate are building minerals essential for bone structure, quality, and resistance whereas some trace elements (i.e.

[65] 1 60 Right femoral diaphysis (Taken after initial, right fra

[65] 1 60 Right Selleckchem SCH727965 femoral diaphysis (Taken after initial, right fracture) Minor lateral cortical thickening on left femur Yes Mild pain in right thigh before right fracture, none before left fracture Yes (GIO) ALN 8 Pred   Left femoral diaphysis (2 years later) Giusti et al. [50] 8 60 Right subtrochanteric femur   Yes Pain in right hip No

ALN 4 Ca, D, pred, inhaled GCs, esomeprazole, repaglinide, metformine, azathioprine, rosuvastatin No (6) Left subtrochanteric Selleck Saracatinib femur (9 months later) 36 Femoral shaft   No   Yes ALN 8 D, pred, simvastatine, cyclosporine, amlopidine, atenolol, lisinopril Yes 64 Left and right subtrochanteric femur (1 complete, 1 insufficiency ABT-263 molecular weight fracture)   Yes Pain in right thigh No ALN 2.5 Ca, D, pred, omeprazole, azathioprine, losartan, triamteren, HCT No (18) 62 Right and left femoral shaftb   Yes Pain in right thigh and hip Yes Oral

pamidronate 4 Ca, D, Yes 58 Femoral shaft   No Pain in left thigh Yes Intravenous pamidronate 3 Ca, D No (12) 58 Subtrochanteric femur   No Pain in left hip No RIS 5.5 Ca, D, pred, inhaled GCs, omeprazole, pravastatine, ibuprofen No (12) 72 Left subtrochanteric femur   Yes Pain in left thigh and hip Yes (GIO) Oral pamidronate followed by ALN 7 + 5 Ca, D, inhaled GCs, esomeprazole, simvastatine, captopril, irbesartan, clopidogrel Yes (12) Right subtrochanteric femur (insufficiency fracture 1 year later) 75 Femoral shaft (insufficiency fracture)     Severe pain

in left thigh and hip Yes RIS 6 Ca, D, esomeprazole, etoricoxib   Femoral shaft (insufficiency fracture 1 year later) Pain in hip ALN alendronate, BP bisphosphonate, Ca calcium, D vitamin D, FS femoral shaft, GCs glucocorticoids, GIO glucocorticoid-induced osteoporosis, HCT hydrochlorothiazide, PF proximal femur, RIS risedronate, ST subtrochanteric, Pred prednisone aMale patient bFirst fracture prior to GBA3 BP treatment; contralateral fracture following 4 years’ BP treatment; refracture of contralateral femoral shaft 4 years after second fracture cPatient was prescribed alendronate in 1996 and took it for 6 years. Fracture occurred 1 year after discontinuation and had not completely healed when reported in 2006 dPatient began teriparatide immediately after fracture In addition to case reports, several case reviews have been published, which are summarized in Table 2.