AimsNovel cell-based therapeutic angiogenic treatments for patients with critical limb ischemia may afford limb salvage. Mesenchymal stem cells (MSCs) do not overexpress E-selectin; however, we have previously demonstrated the cell-adhesion molecule's vital role in angiogenesis and wound healing. Thus, we created a viral vector to overexpress E-selectin on MSCs to increase their therapeutic profile.Methods and ResultsFemoral artery ligation induced hind limb ischemia in mice and intramuscular injections were administered of vehicle or syngeneic donor MSCs, transduced ex vivo with an adeno-associated viral vector to express either GFP+ (MSCGFP) or E-selectin-GFP+ (MSCE−selectin−GFP). Laser Doppler Imaging demonstrated significantly restored reperfusion in MSCE−selectin−GFP-treated mice vs. controls. After 3 weeks, the ischemic limbs in mice treated with MSCE−selectin−GFP had increased footpad blood vessel density, hematoxylin and eosin stain (H&E) ischemic calf muscle sections revealed mitigated muscular atrophy with restored muscle fiber size, and mice were able to run further before exhaustion. PCR array-based gene profiling analysis identified nine upregulated pro-angiogenic/pro-repair genes and downregulated Tumor necrosis factor (TNF) gene in MSCE−selectin−GFP-treated limb tissues, indicating that the therapeutic effect is likely achieved via upregulation of pro-angiogenic cytokines and downregulation of inflammation.ConclusionThis innovative cell therapy confers increased limb reperfusion, neovascularization, improved functional recovery, decreased muscle atrophy, and thus offers a potential therapeutic method for future clinical studies.
a b s t r a c tPurpose: Child abuse is a national, often hidden, epidemic. The study objective was to determine at-risk populations that have been previously hospitalized prior to their admission for child abuse. Methods: The Nationwide Readmissions Database (NRD) was queried for all children hospitalized for abuse. Outcomes were previous admissions and diagnoses. χ 2 analysis was used; significance equals p b 0.05. Results: 31,153 children were hospitalized for abuse (half owing to physical abuse) during the study period. 11% (n = 3487) of these children had previous admissions (one in three to a different hospital), while 3% (n = 1069) had multiple hospitalizations. 60% of prior admissions had chronic conditions, and 12% had traumatic injuries. Children with chronic conditions were more likely to have sexual abuse (89% vs. 57%, p b 0. 001) and emotional abuse (75% vs. 60%, p b 0. 01). 25% of chronic diagnoses were psychiatric, who were also more likely to have sexual and emotional abuse (47% vs. 5.5% and 10% vs. 1%, all p b 0. 001). Conclusion: This study uncovers a hidden population of children with past admissions for chronic conditions, especially psychiatric diagnoses that are significantly associated with certain types of abuse. Improved measures to accurately identify at-risk children must be developed to prevent future childhood abuse and trauma. Level of evidence: Level III. Type of study: Retrospective comparative study.
Gastrointestinal stromal tumors are exceedingly rare tumors in the pediatric population, as a result many clinicians either may never see this diagnosis or will encounter it only a few times throughout their careers. It is imperative in the pediatric population to follow appropriate steps to ensure a swift diagnosis and referral to specialized centers that are equipped with the multidisciplinary teams accustomed to treating rare diseases. This review aims to discuss the most recent data available on the diagnostic modalities utilized in cases of suspected Pediatric GIST.
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