Optimizing the synthesis of interleukin-12-loaded PLGA nanospheres (rmIL-12ns) via ultrasonication for treatment of metastatic osteosarcoma.

Clinical trials exploring bolus intravenous delivery of interleukin-12 (IL-12) for treatment of solid tumors ultimately failed due to lack of clinical response and severe dose-limiting toxicities. The present study was conducted to evaluate whether recombinant murine IL-12 (rmIL-12) could be successfully encapsulated within Poly (D, l-lactide-co-glycolide) (PLGA) nanospheres (rmIL-12ns) for safe and effective systemic delivery at pharmacologic scale. Optimal fabrication of rmIL-12ns occurs with dichloromethane as the organic solvent and emulsion formation via ultrasonication at 50% power (250 W sonicator) for 10 s (50W10s). We then determined whether utilization of synthesis modifiers including fetal bovine serum (FBS), magnesium hydroxide [Mg(OH)2 ], trehalose, or the surfactants polysorbate 80 and Span 60 alone or in combination could increase the encapsulation efficiency (EE) and/or modify the burst elution profile characteristic of the 50W10s rmIL-12ns formulation. The greatest EEs compared to the unmodified formulation were measured with modifications containing the surfactants polysorbate 80 and Span 60 (surfactant: 28.3 ± 6.10%, p = 0.29 and Surf/FBS: 85.4 ± 2.19%, p = 0.039). The Surf/FBS formulation was further modified for in vivo murine injection by substituting FBS with mouse serum albumin (MSA). The resulting Surf/MSA rmIL-12ns were then characterized before delivery at three doses (0.1, 1, and 10 mg rmIL-12ns) in our established murine model of metastatic osteosarcoma to assess efficacy. Preliminary results suggested no evidence of disease with delivery of the 0.1 mg dose in 75% of mice (3 of 4) versus a nontreated historical control (2 of 34).

Relevance of Medullary Vein Sign in Neurosarcoidosis.

BACKGROUND: Central nervous system involvement is uncommon in patients with sarcoidosis. It remains a diagnostic challenge for clinicians, as there is a broad differential diagnosis that matches the presenting neurological signs. Often, the imaging findings also overlap with other disease entities. One understudied finding in patients with neurosarcoidosis is the presence of medullary vein engorgement on SWI imaging, termed the "medullary vein sign", which has been postulated to be a specific sign for neurosarcoidosis. This study aims to provide an understanding of the diagnostic potential of the medullary vein sign. METHODS: Thirty-two patients who presented with neurologic signs concerning for possible neurosarcoidosis were analyzed retrospectively for the presence of the medullary vein sign. RESULTS: Out of these cases, 7 cases of definitive neurosarcoidosis cases were found based on other imaging signs, biopsy and CSF analysis; the remaining were classified into groups as possible (16), probable (5) and (4) cases of other infectious meningoencephalitis including 2 cases of autoimmune encephalitis. Seven patients among all of these cases were found to have the medullary vein sign on imaging, with five cases with confirmed and two cases from possible neurosarcoidosis. The sensitivity of the medullary vein sign in this study was 71.4%, and the specificity was 92.3%. DISCUSSION: The benefits of improving diagnostic criteria for neurosarcoidosis include more rapid diagnosis leading to more prompt treatment, less exposure to potentially harmful antibiotics or antifungals, and less long-term neurological effects. Our results support that the medullary vein sign will potentially fill in the diagnostic gaps that have challenged the timely diagnosis of neurosarcoidosis. CONCLUSIONS: Our findings support that the medullary vein sign has a high specificity and should be included in the diagnostic criteria for neurosarcoidosis.

Risk of Cardiovascular Disease in Male Farmers Over the Age of 45: A Review of Literature.

The prevalence of heart disease in farmers is well documented, but there is limited research characterizing the diverse risk factors associated specifically with male farmers over the age of 45 in the United States, while also providing a multifactorial strategy to address these concerns. The majority of current research either focuses on the general rural population or does not take into account different demographic variables. Hence, this review looked to address those gaps by focusing on those specific variables. A literature review was generated looking at risk factors associated with cardiovascular disease in farmers using key search terms. Next, an additional search was conducted focusing on treatment plans to address these concerns. The articles were then sorted based on the inclusion and exclusion criteria. The initial articles were sorted by one researcher and then reassessed on two separate occasions. The literature review was performed using these databases: PubMed, CINAHL, Cochrane, and Ovid Medline. A total of 221 articles were generated, of which 12 articles matched the criteria. The articles highlighted important risk factors that were either social or non-social determinants of health that negatively impacted the target population. These were followed up by offering solutions that attempted to provide a holistic approach, including clinical and community-based interventions. Male farmers over the age of 45 years are at an increased risk of being diagnosed with heart disease compared to non-farmers in the same demographic. When attempting to implement interventions, stress management should be incorporated into the treatment plan. In addition, a multifaceted approach targeting clinical and community concerns is recommended.