Matrix modification for enhancing the transport properties of the human cartilage endplate to improve disc nutrition.

Poor solute transport through the cartilage endplate (CEP) impairs disc nutrition and could be a key factor that limits the success of intradiscal biologic therapies. Here we demonstrate that treating the CEP with matrix metalloproteinase-8 (MMP-8) reduces the matrix constituents that impede solute uptake and thereby improves nutrient diffusion. Human CEP tissues harvested from four fresh cadaveric lumbar spines (age range: 38-66 years old) were treated with MMP-8. Treatment caused a dose-dependent reduction in sGAG, localized reductions to the amount of collagen, and alterations to collagen structure. These matrix modifications corresponded with 16-24% increases in the uptake of a small solute (376 Da). Interestingly, the effects of MMP-8 treatment depended on the extent of non-enzymatic glycation: treated CEPs with high concentrations of advanced glycation end products (AGEs) exhibited the lowest uptake compared to treated CEPs with low concentrations of AGEs. Moreover, AGE concentrations were donor-specific, and the donor tissues with the highest AGE concentrations appeared to have lower uptake than would be expected based on the initial amounts of collagen and sGAG. Finally, increasing solute uptake in the CEP improved cell viability inside diffusion chambers, which supports the nutritional relevance of enhancing the transport properties of the CEP. Taken together, our results provide new insights and in vitro proof-of-concept for a treatment approach that could improve disc nutrition for biologic therapy: specifically, matrix reduction by MMP-8 can enhance solute uptake and nutrient diffusion through the CEP, and AGE concentration appears to be an important, patient-specific factor that influences the efficacy of this approach

The Grizzly, February 2, 1979

Frat Beating Draws Administrative Fire • New Frat Gathers Steam • Holiday Thefts: Negligence or Lack of Concern? • In Memoriam • Judiciary Board Revival • Cultural Kaleidoscope • Letters to the Editor: Snack shop complaint • Roving Reporter: Greaseband opinions • Dishroom Profile: Roy Schuetz, Man or Myth? • Grease Is The Word • Nicolette Larson Debuts In Style • USGA Elections • Portrait of the Professor: Dr. Conrad E. Kruse • Raquetball Review • Bio Club Spawned • R.A. Applications Available; Ruby Seeks Editor • Gymnasts Place Third In Tourney • Bears Turning Corner • Slavin Breaks Record Mermaids Lose • Wrestlers Manhandle Mules • Badminton Drops Onehttps://digitalcommons.ursinus.edu/grizzlynews/1011/thumbnail.jp

Civil Society, Everyday Life and the Possibilities for Development Studies

Civil society is one of the most contentious terms in political thought. There is considerable, and highly significant, difference between academic debate about the meaning of ‘civil society’ and the way the term is mobilized in international development discourse. In particular, narratives of civil society in international development are often dominated by reference to organizational descriptions and measurability. But I would like to suggest here that the term should be reclaimed as a way of giving meaning to the stories of the everyday lives of the people who create, shape and embody civil society. Used in this way, the idea of civil society can be understood as intersecting emotions, discourses and practices and can add to the body of scholarly work that nurtures and values everyday life as a lens through which to view wider social processes. Paying attention to the everyday life of civil society may have implications for that way the civil society is engaged with academically, and also has the potential to refresh how civil society is thought about in development practice

Long-Term Efficacy and Safety of Adalimumab in Pediatric Patients with Crohn's Disease

Background: IMAgINE 1 assessed 52-week efficacy and safety of adalimumab in children with moderate to severe Crohn's disease. Long-Term efficacy and safety of adalimumab for patients who entered the IMAgINE 2 extension are reported. Methods: Patients who completed IMAgINE 1 could enroll in IMAgINE 2. Endpoints assessed from weeks 0 to 240 of IMAgINE 2 were Pediatric Crohn's Disease Activity Index remission (Pediatric Crohn's Disease Activity Index ≤ 10) and response (Pediatric Crohn's Disease Activity Index decrease ≥15 from IMAgINE 1 baseline) using observed analysis and hybrid nonresponder imputation (hNRI). For hNRI, discontinued patients were imputed as failures unless they transitioned to commercial adalimumab (with study site closure) or adult care, where last observation was carried forward. Corticosteroid-free remission in patients receiving corticosteroids at IMAgINE 1 baseline, discontinuation of immunomodulators (IMMs) in patients receiving IMMs at IMAgINE 2 baseline, and linear growth improvement were reported as observed. Adverse events were assessed for patients receiving ≥1 adalimumab dose in IMAgINE 1 and 2 through January 2015. Results: Of 100 patients enrolled in IMAgINE 2, 41% and 48% achieved remission and response (hNRI) at IMAgINE 2 week 240. Remission rates were maintained by 45% (30/67, hNRI) of patients who entered IMAgINE 2 in remission. At IMAgINE 2 week 240, 63% (12/19) of patients receiving corticosteroids at IMAgINE 1 baseline achieved corticosteroid-free remission and 30% (6/20) of patients receiving IMMs at IMAgINE 2 baseline discontinued IMMs. Adalimumab treatment led to growth velocity normalization. No new safety signals were identified. Conclusions: Efficacy and safety profiles of prolonged adalimumab treatment in children with Crohn's disease were consistent with IMAgINE 1 and adult Crohn's disease adalimumab trials

Next-Generation Sequencing Reveals High Concordance of Recurrent Somatic Alterations Between Primary Tumor and Metastases From Patients With Non-Small-Cell Lung Cancer

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