Ameliorative Effect and Underlying Mechanisms of Total Triterpenoids from Psidium guajava Linn (Myrtaceae) Leaf on High-Fat Streptozotocin-induced Diabetic Peripheral Neuropathy in Rats

Purpose: To investigate whether the total triterpenoids extracted from Psidium Guajava leaves (TTPGL) attenuate the development of diabetic peripheral neuropathy in rats by regulating the NF-κB pathway of the inflammatory process and its signaling mediators.Methods: All the Sprague Dawley rats used were maintained in a clean environment on a 12 h light/12h dark cycle. High-fat feeding and intraperitoneal injection of 40 mg/kg streptozotocin (STZ) were used to induce diabetes in the rats. The rats were randomly divided into 5 groups: diabetic mellitus (DM) group; TTPGL - 30 group, TTPGL - 60 group and TTPGL - 120 group treated by intragastric administration (i.g) with 30, 100 and 120 mg/kg/day TTPGL, respectively. The well-established drug, rosiglitazone (RSG, 3 mg/k/d, i.g.), was used as positive control. Normal rats served as control group. Nerve conduction velocity and sensitive tests were measured on weeks 1, 4 and 8. After 8 weeks administration, expression of pro-inflammatory molecules (TNF - α, IL - 6 and iNOS) and tissue proteins (Akt, IKKα, and NF – κB - p65) were evaluated to assess biochemical changes.Results: Compared to DM group, TTPGL (especially 120 mg / kg dose) treatment improved (p < 0.05) physical functions and provided neuronal protection in high - fat/streptozotocin - induced peripheral neuropathy rats. We found that the expressions of several pro - inflammatory factors such as tumor necrosis factor - α (TNF - α), IL - 6 and inducible nitric oxide synthase (iNOS) were highly suppressed (p < 0.05 or p < 0.01) by TTPGL in sciatic nerve. Mechanism analysis indicated that the ameliorative effect of TTPGL, in part, is through suppression of the expression of pro - inflammatory cytokines by NF - κB pathway mediation.Conclusion: TTPGL offers a potential therapeutic approach for the treatment of diabetic peripheral neuropathy.Keywords: Triterpenoids, Psidium Guajava, Diabetic peripheral neuropathy, Pro inflammatory cytokines, NF-κB pathwa

Fund for Shared Insight: Media Analysis

Fund for Shared Insight ("Shared Insight") is a collaborative effort among fundersthat pools financial and other resources to make grants to improve philanthropy. Shared Insight believes philanthropy can have a greater social and environmental impact if foundations and nonprofits listen to the people they seek to help, act on what they hear, and openly share what they learn.Related to feedback loops, Shared Insight's work is focused on increasingthe extent to which foundations listen to others—especially the people they seek to help—and respond to their expressed interests. When Shared Insight talks about "the people they seek to help," they are referring to the individuals who receive programs and services from nonprofit organizations; for example, the students served by charter schools, the recently released prisoners benefiting from job-training services, and the low-income first-time mothers participating in prenatal through birth programs.Over the next three years, Shared Insight would hope to see changes in the amount and kind of discourse in the field related tobeneficiary feedback loops. In the summer of 2015, one year since the launch of the collaborative, ORS Impact repeated a media analysis of relevant blogs, periodicals, and reports. The following memo outlines changes in the amount and kind of discourse in the field around feedback loops compared to the year before Shared Insight launched. We raise a few observations and considerations. More detailed methodological notes follow

Overall survival.

<p>The outcomes of the univariate analysis of risk factors influencing the perioperative flap survival rate. The univariate analysis was performed using the Kaplan-Meier method coupled with a log-rank test.</p

Reconstruction of the Foot and Ankle Using Pedicled or Free Flaps: Perioperative Flap Survival Analysis

<div><p>Objective</p><p>The purpose of this study is to determine the correlation between non-technical risk factors and the perioperative flap survival rate and to evaluate the choice of skin flap for the reconstruction of foot and ankle.</p><p>Methods</p><p>This was a clinical retrospective study. Nine variables were identified. The Kaplan-Meier method coupled with a log-rank test and a Cox regression model was used to predict the risk factors that influence the perioperative flap survival rate. The relationship between postoperative wound infection and risk factors was also analyzed using a logistic regression model.</p><p>Results</p><p>The overall flap survival rate was 85.42%. The necrosis rates of free flaps and pedicled flaps were 5.26% and 20.69%, respectively. According to the Cox regression model, flap type (hazard ratio [HR] = 2.592; 95% confidence interval [CI] (1.606, 4.184); P < 0.001) and postoperative wound infection (HR = 0.266; 95% CI (0.134, 0.529); P < 0.001) were found to be statistically significant risk factors associated with flap necrosis. Based on the logistic regression model, preoperative wound bed inflammation (odds ratio [OR] = 11.371,95% CI (3.117, 41.478), P < 0.001) was a statistically significant risk factor for postoperative wound infection.</p><p>Conclusion</p><p>Flap type and postoperative wound infection were both independent risk factors influencing the flap survival rate in the foot and ankle. However, postoperative wound infection was a risk factor for the pedicled flap but not for the free flap. Microvascular anastomosis is a major cause of free flap necrosis. To reconstruct complex or wide soft tissue defects of the foot or ankle, free flaps are safer and more reliable than pedicled flaps and should thus be the primary choice.</p></div

Multivariate Cox model results for predictive factors of pedicled flap (n = 87) necrosis

<p>Multivariate Cox model results for predictive factors of pedicled flap (n = 87) necrosis</p

Multivariate Cox model results for predictive factors of free flap (n = 55) necrosis

<p>Multivariate Cox model results for predictive factors of free flap (n = 55) necrosis</p

A 49-year-old male patient suffered from a mutilating forefoot injury, and the forefoot was reconstructed using the contralateral free plantar medial flap.

<p>a, Mutilating forefoot injury; b, after forefoot debridement; c and d, design and harvesting of free medial plantar flap; e and f, PN of the flap on the sixth postoperative day.</p

The results of the 144 skin flaps

<p>The results of the 144 skin flaps</p