Novel bisphosphonate-based cathepsin K-triggered compound targets the enthesis without impairing soft tissue-to-bone healing

Background: Osteoadsorptive fluorogenic sentinel 3 (OFS-3) is a recently described compound that contains a bone-targeting bisphosphonate (BP) and cathepsin K (Ctsk)-triggered fluorescence signal. A prior study in a murine Achilles repair model demonstrated its effectiveness at targeting the site of tendon-to-bone repair, but the intrinsic effect of this novel bisphosphonate chaperone on tendon-to-bone healing has not been previously explored. We hypothesized that application of this bisphosphonate-fluorophore cargo conjugate would not affect the biomechanical properties or histologic appearance of tendon-bone repairs.Materials and Methods: Right hindlimb Achilles tendon-to-bone repair was performed on 12-week old male mice. Animals were divided into 2 groups of 18 each: 1) Achilles repair with OFS-3 applied directly to the repair site prior to closure, and 2) Achilles repair with saline applied prior to closure. Repaired hindlimbs from 12 animals per group were harvested at 6 weeks for biomechanical analysis with a custom 3D-printed jig. At 4 and 6 weeks, repaired hindlimbs from the remaining animals were assessed histologically using H&E, immunohistochemistry (IHC) staining for the presence of Ctsk, and second harmonic generation (SHG) imaging to evaluate collagen fibers.Results: At 6 weeks, there was no significant difference in failure load, stiffness, toughness, or displacement to failure between repaired hindlimbs that received OFS-3 versus saline. There was no difference in tissue healing on H&E or Ctsk staining on immunohistochemistry between animals that received OFS-3 versus saline. Finally, second harmonic generation imaging demonstrated no difference in collagen fiber parameters between the two groups.Conclusion: OFS-3 did not significantly affect the biomechanical properties or histologic appearance of murine Achilles tendon-to-bone repairs. This study demonstrates that OFS-3 can target the site of tendon-to-bone repair without causing intrinsic negative effects on healing. Further development of this drug delivery platform to target growth factors to the site of tendon-bone repair is warranted

Painted Women: Male Representations of Prostitutes in 19th Century American and French Literature and Visual Art

This thesis explores how 19th century American and French male literary and visual artists’ representations of prostitutes channel men’s anxieties about the economic positions of women in the modernizing cities of New York City and Paris. The first chapter asserts that Stephen Crane’s Maggie: A Girl of the Streets (1893) depicts how the patriarchal capitalist system oppresses the prostitute, Maggie, and actual women of her era. The second chapter demonstrates how Emile Zola’s Nana (1880) voices male fears about the capacity of female merchants, such as Nana, a prostitute who sells her body, and individuals of the popular class to disturb the socioeconomic hierarchy by usurping power traditionally held by aristocratic and bourgeois men. The third chapter analyzes the paintings of John Sloan, an American painter, who depicts prostitutes in “The Women’s Night Court: Before Her Makers and Her Judge,” (1913) 1 “Putting the Best Foot Forward,” (1913) 2 and “Three a.m.” (1909). 3 This chapter additionally examines “Nana” (1877) 4 and “Olympia,” (1863) 5 works that also represent prostitutes by French painter Edouard Manet. The chapter claims that these paintings, similar to the aforementioned literary works, uphold the stereotypes of women embedded in the literary works while granting women more control over their bodies. While the American tradition highlights the prostitute as a victim of the patriarchal economy and at best an actor within it, the French tradition proposes that the prostitute threatens the patriarchal economic system. Overall, this thesis argues that the literary and visual representations of prostitutes in New York City and Paris channel male observations and concerns about the power of women within their respective, modernizing patriarchal economies

Novel bisphosphonate-based cathepsin K-triggered compound targets the enthesis without impairing soft tissue-to-bone healing

Background: Osteoadsorptive fluorogenic sentinel 3 (OFS-3) is a recently described compound that contains a bone-targeting bisphosphonate (BP) and cathepsin K (Ctsk)-triggered fluorescence signal. A prior study in a murine Achilles repair model demonstrated its effectiveness at targeting the site of tendon-to-bone repair, but the intrinsic effect of this novel bisphosphonate chaperone on tendon-to-bone healing has not been previously explored. We hypothesized that application of this bisphosphonate-fluorophore cargo conjugate would not affect the biomechanical properties or histologic appearance of tendon-bone repairs. Materials and Methods: Right hindlimb Achilles tendon-to-bone repair was performed on 12-week old male mice. Animals were divided into 2 groups of 18 each: 1) Achilles repair with OFS-3 applied directly to the repair site prior to closure, and 2) Achilles repair with saline applied prior to closure. Repaired hindlimbs from 12 animals per group were harvested at 6 weeks for biomechanical analysis with a custom 3D-printed jig. At 4 and 6 weeks, repaired hindlimbs from the remaining animals were assessed histologically using H&E, immunohistochemistry (IHC) staining for the presence of Ctsk, and second harmonic generation (SHG) imaging to evaluate collagen fibers. Results: At 6 weeks, there was no significant difference in failure load, stiffness, toughness, or displacement to failure between repaired hindlimbs that received OFS-3 versus saline. There was no difference in tissue healing on H&E or Ctsk staining on immunohistochemistry between animals that received OFS-3 versus saline. Finally, second harmonic generation imaging demonstrated no difference in collagen fiber parameters between the two groups. Conclusion: OFS-3 did not significantly affect the biomechanical properties or histologic appearance of murine Achilles tendon-to-bone repairs. This study demonstrates that OFS-3 can target the site of tendon-to-bone repair without causing intrinsic negative effects on healing. Further development of this drug delivery platform to target growth factors to the site of tendon-bone repair is warranted

The Right to Play Versus the Right to War? Vulnerable Childhood in Lebanon’s NGOization

International audienceIn the wake of the massive human displacement from Syria (2011–), some international NGOs (INGOs) have intervened in Lebanon to prevent Lebanese and Syrian youth from “radicalizing” and joining armed groups. In the framework of international humanitarian assistance within the “Global South,” while refugee adults are expected to become self-reliant, children and youth are often addressed as objects of universal concern and rarely as aware subjects of decision-making. Drawing on interviews conducted between Spring 2015 and Autumn 2016 with INGO workers and child players and their parents, we consider INGO play activities in contexts where political violence is widespread and longstanding, such as the Tripoli governorate in northern Lebanon. This chapter first aims to unpack the INGO discourse on children’s vulnerability. Second, we analyze INGO discourses and practices in a bid to critically examine the humanitarian and developmental attempts at providing politically neutral spaces for refugee and local children. We therefore build a threefold analysis focusing on the dehistoricization of political violence in the Arab Levant, the employment of the “Sport for Development” formula as a path to social cohesion, and the weak cultural literacy of INGOs in regard to contextual adult-child relations. Thereby, we argue that while INGOs tend to commodify the child as an a priori humanitarian victim, the international assistance community should rather strive to provide children with alternate avenues for political engagement in order to counter war recruitment

Age and frailty are independently associated with increased COVID-19 mortality and increased care needs in survivors: results of an international multi-centre study

Introduction: Increased mortality has been demonstrated in older adults with coronavirus disease 2019 (COVID-19), but the effect of frailty has been unclear. Methods: This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS) and delirium on risk of increased care requirements on discharge, adjusting for the same variables. Results: Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, interquartile range [IQR] 54–83; 55.2% male). The risk of death increased independently with increasing age (>80 versus 18–49: hazard ratio [HR] 3.57, confidence interval [CI] 2.54–5.02), frailty (CFS 8 versus 1–3: HR 3.03, CI 2.29–4.00) inflammation, renal disease, cardiovascular disease and cancer, but not delirium. Age, frailty (CFS 7 versus 1–3: odds ratio 7.00, CI 5.27–9.32), delirium, dementia and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. Conclusion: Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age.</p