Plasticity After Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It

Motor, sensory, and autonomic functions can spontaneously return or recover to varying extents in both humans and animals, regardless of the traumatic spinal cord injury (SCI) level and whether it was complete or incomplete. In parallel, adverse and painful functions can appear. The underlying mechanisms for all of these diverse functional changes are summarized under the term plasticity. Our review will describe what is known regarding this phenomenon after traumatic SCI and focus on its relevance to motor and sensory recovery. Although it is still somewhat speculative, plasticity can be found throughout the neuraxis and includes various changes ranging from alterations in the properties of spared neuronal circuitries, intact or lesioned axon collateral sprouting, and synaptic rearrangements. Furthermore, we will discuss a selection of potential approaches for facilitating plasticity as possible SCI treatments. Because a mechanism underlying spontaneous plasticity and recovery might be motor activity and the related neuronal activity, activity-based therapies are being used and investigated both clinically and experimentally. Additional pharmacological and gene-delivery approaches, based on plasticity being dependent on the delicate balance between growth inhibition and promotion as well as the basic intrinsic growth ability of the neurons themselves, have been found to be effective alone and in combination with activity-based therapies. The positive results have to be tempered with the reality that not all plasticity is beneficial. Therefore, a tremendous number of questions still need to be addressed. Ultimately, answers to these questions will enhance plasticity’s potential for improving the quality of life for persons with SCI.     

Tumor Angiogenesis Phenotyping by Nanoparticle-facilitated Magnetic Resonance and Near-infrared Fluorescence Molecular Imaging

One of the challenges of tailored antiangiogenic therapy is the ability to adequately monitor the angiogenic activity of a malignancy in response to treatment. The α_vβ₃ integrin, highly overexpressed on newly formed tumor vessels, has been successfully used as a target for Arg-Gly-Asp (RGD)-functionalized nanoparticle contrast agents. In the present study, an RGD-functionalized nanocarrier was used to image ongoing angiogenesis in two different xenograft tumor models with varying intensities of angiogenesis (LS174T > EW7). To that end, iron oxide nanocrystals were included in the core of the nanoparticles to provide contrast for T₂*-weighted magnetic resonance imaging (MRI), whereas the fluorophore Cy7 was attached to the surface to enable near-infrared fluorescence (NIRF) imaging. The mouse tumor models were used to test the potential of the nanoparticle probe in combination with dual modality imaging for in vivo detection of tumor angiogenesis. Pre-contrast and post-contrast images (4 hours) were acquired at a 9.4-T MRI system and revealed significant differences in the nanoparticle accumulation patterns between the two tumor models. In the case of the highly vascularized LS174T tumors, the accumulation was more confined to the periphery of the tumors, where angiogenesis is predominantly occurring. NIRF imaging revealed significant differences in accumulation kinetics between the models. In conclusion, this technology can serve as an in vivo biomarker for antiangiogenesis treatment and angiogenesis phenotyping.     

The impact of class III (morbid) obesity on heterotopic ossification outcomes

PurposeObesity is associated with a chronic low inflammatory process that may act as common soil for the pathogenesis of obesity-related comorbidities including heterotopic ossification (HO). The purpose of this study is to compare the incidence of HO between patients with body mass index (BMI) <40 versus ≥40 after operative treatment of displaced acetabular fractures followed by radiation therapy (RT) ± indomethacin.Methods and MaterialsThis is a single institution retrospective chart review of 419 patients. All patients with well-documented BMI underwent operative treatment followed by RT ± indomethacin. All patients received 700 cGy to the soft tissues around the proximal femur and acetabulum without bone shielding. All RT were given postoperatively within 72 hours. The patients were divided into 2 groups: Group (A) BMI < 40 and Group (B) BMI ≥40. HO was assessed with X-ray. BMI was used as a surrogate measure to test the risk of HO despite prophylaxis.ResultsThe incidence of HO among all patients is 21% (89 of 419), while among those in group A (BMI <40), 68 of 374 patients developed HO (18%); in the morbidly obese group (BMI ≥40) 21of 45 patients developed HO (47%). The difference between the rates of HO in the 2 groups was 29%; the χ² test showed a significant difference between the 2 BMI groups (P < .001 at α = 0.05).ConclusionsThere is a higher incidence of HO among the morbidly obese patients despite RT ± indomethacin. RT doses for HO prophylaxis in morbidly obese patients need to be reassessed; also, understanding the signaling pathways in target tissues in obese patients at which adipokines control metabolism may reveal novel therapies. Higher radiation doses ± indomethacin may need to be considered and optimally evaluated in the context of a prospective, randomized clinical trial.     

Use of evidence to support healthy public policy: a policy effectiveness�Cfeasibility loop

Public policy plays a key role in improving population health and in the control of diseases, including non-communicable diseases. However, an evidence-based approach to formulating healthy public policy has been difficult to implement, partly on account of barriers that hinder integrated work between researchers and policy-makers. This paper describes a “policy effectiveness–feasibility loop” (PEFL) that brings together epidemiological modelling, local situation analysis and option appraisal to foster collaboration between researchers and policy-makers. Epidemiological modelling explores the determinants of trends in disease and the potential health benefits of modifying them. Situation analysis investigates the current conceptualization of policy, the level of policy awareness and commitment among key stakeholders, and what actually happens in practice, thereby helping to identify policy gaps. Option appraisal integrates epidemiological modelling and situation analysis to investigate the feasibility, costs and likely health benefits of various policy options. The authors illustrate how PEFL was used in a project to inform public policy for the prevention of cardiovascular diseases and diabetes in four parts of the eastern Mediterranean. They conclude that PEFL may offer a useful framework for researchers and policy-makers to successfully work together to generate evidence-based policy, and they encourage further evaluation of this approach.     

Cystatin C: a predictor of hepatorenal syndrome in patients with liver cirrhosis

Background  

Recent studies suggest that serum cystatin C (CysC) is a more sensitive marker of renal functions than serum creatinine (Cr).