Piloting a Layperson Prehospital Care System in Rural Uganda.

INTRODUCTION: In many low-income countries, basic prehospital Emergency Medical Services (EMS) remain under-developed, resulting in significant delays or the complete inability to access care. STUDY OBJECTIVE: The purpose of this study was to analyze the effectiveness of a layperson EMS training targeting motorcycle taxi (boda) drivers in a rural region of Uganda. METHODS: Fifty (50) adult boda drivers from Masindi, Uganda were selected for a one-day training course including lectures and simulation. Course content covered basic prehospital skills and transport. Participants were given a first responder kit at completion of the course. Understanding of material was assessed prior to training, immediately after course completion, and four months from the initial course using the same ten question test. Test means were analyzed using a standard linear regression model. At the four-month follow up, all 50 boda drivers participated in semi-structured small group qualitative interviews regarding their perception of the course and experiences implementing course skills in the community. Boda drivers were asked to complete a brief form on each patient transported during the study period. For patients transported to Masindi Kitara Medical Center (MKMC), hospital trauma registry data were analyzed. RESULTS: Trainees showed both knowledge acquisition and retention with pre-test scores of 21.8% improving to 48.0% at course completion and 57.7% at the four-month follow up. Overall, participant's scores increased by an average of 35% from the pre-test to the second post-test (P <.001). A total of 69 patient forms were completed on transported patients over the initial four-month period. Ninety-five percent (95%) of these were injured patients, and motorcycle crash was the predominant mechanism of injury (48% of injuries). Eight patients were transported to MKMC, but none of these patients were recorded in the hospital trauma registry. Major barriers identified through semi-structured interviews included harassment by police, poor road conditions, and lack of basic resources for transport. Ninety-four percent (94%) of trainees strongly agreed that the training was useful. Total costs were estimated at $3,489 USD, or $69 per trainee. CONCLUSION: Motorcycle taxi drivers can be trained to provide basic prehospital care in a short time and at a low cost. While there is much enthusiasm for additional training and skill acquisition from this cohort, the sustainability and scalability of such programs is still in question.

Neoadjuvant Therapy Is Associated with Improved Chemotherapy Delivery and Overall Survival Compared to Upfront Resection in Pancreatic Cancer without Increasing Perioperative Complications.

The role of neoadjuvant chemoradiotherapy and/or chemotherapy (neoCHT) in patients with pancreatic ductal adenocarcinoma (PDAC) is poorly defined. We hypothesized that patients who underwent neoadjuvant therapy (NAT) would have improved systemic therapy delivery, as well as comparable perioperative complications, compared to patients undergoing upfront resection. This is an IRB-approved retrospective study of potentially resectable PDAC patients treated within an academic quaternary referral center between 2011 and 2018. Data were abstracted from the electronic medical record using an institutional cancer registry and the National Surgical Quality Improvement Program. Three hundred and fourteen patients were eligible for analysis and eighty-one patients received NAT. The median overall survival (OS) was significantly improved in patients who received NAT (28.6 vs. 20.1 months, p = 0.014). Patients receiving neoCHT had an overall increased mean duration of systemic therapy (p < 0.001), and the median OS improved with each month of chemotherapy delivered (HR = 0.81 per month CHT, 95% CI (0.76-0.86), p < 0.001). NAT was not associated with increases in early severe post-operative complications (p = 0.47), late leaks (p = 0.23), or 30-90 day readmissions (p = 0.084). Our results show improved OS in patients who received NAT, driven largely by improved chemotherapy delivery, without an apparent increase in early or late perioperative complications compared to patients undergoing upfront resection.

Measuring the Effects of Cytokines on the Modification of Pericellular Rheology by Human Mesenchymal Stem Cells.

Implantable hydrogels are designed to treat wounds by providing structure and delivering additional cells to damaged tissue. These materials must consider how aspects of the native wound, including environmental chemical cues, affect and instruct delivered cells. One cell type researchers are interested in delivering are human mesenchymal stem cells (hMSCs) due to their importance in healing. Wound healing involves recruiting and coordinating a variety of cells to resolve a wound. hMSCs coordinate the cellular response and are signaled to the wound by cytokines, including transforming growth factor-ß (TGF-ß) and tumor necrosis factor-α (TNF-α), present in vivo. These cytokines change hMSC secretions, regulating material remodeling. TGF-ß, present from inflammation through remodeling, directs hMSCs to reorganize collagen, increasing extracellular matrix (ECM) structure. TNF-α, present primarily during inflammation, cues hMSCs to clear debris and degrade ECM. Because cytokines change how hMSCs degrade their microenvironment and are naturally present in the wound, they also affect how hMSCs migrate out of the scaffold to conduct healing. Therefore, the effects of cytokines on hMSC remodeling are important when designing materials for cell delivery. In this work, we encapsulate hMSCs in a polymer-peptide hydrogel and incubate the scaffolds in media with TGF-ß or TNF-α at concentrations similar to those in wounds. Multiple particle tracking microrheology (MPT) measures hMSC-mediated scaffold degradation in response to these cytokines, which mimics aspects of the in vivo microenvironment post-implantation. MPT uses video microscopy to measure Brownian motion of particles in a material, quantifying structure and rheology. Using MPT, we measure increased hMSC-mediated remodeling when cells are exposed to TNF-α and decreased remodeling after exposure to TGF-ß when compared to untreated hMSCs. This agrees with previous studies that measure: (1) TNF-α encourages matrix reorganization and (2) TGF-ß signals the formation of new matrix. These results enable material design that anticipates changes in remodeling after implantation, improving control over hMSC delivery and healing.

Mercury(II) binds to both of chymotrypsin's histidines, causing inhibition followed by irreversible denaturation/aggregation.

The toxicity of mercury is often attributed to its tight binding to cysteine thiolate anions in vital enzymes. To test our hypothesis that Hg(II) binding to histidine could be a significant factor in mercury's toxic effects, we studied the enzyme chymotrypsin, which lacks free cysteine thiols; we found that chymotrypsin is not only inhibited, but also denatured by Hg(II). We followed the aggregation of denatured enzyme by the increase in visible absorbance due to light scattering. Hg(II)-induced chymotrypsin precipitation increased dramatically above pH 6.5, and free imidazole inhibited this precipitation, implicating histidine-Hg(II) binding in the process of chymotrypsin denaturation/aggregation. Diethylpyrocarbonate (DEPC) blocked chymotrypsin's two histidines (his40 and his57 ) quickly and completely, with an IC50 of 35 ± 6 µM. DEPC at 350 µM reduced the hydrolytic activity of chymotrypsin by 90%, suggesting that low concentrations of DEPC react with his57 at the active site catalytic triad; furthermore, DEPC below 400 µM enhanced the Hg(II)-induced precipitation of chymotrypsin. We conclude that his57 reacts readily with DEPC, causing enzyme inhibition and enhancement of Hg(II)-induced aggregation. Above 500 µM, DEPC inhibited Hg(II)-induced precipitation, and [DEPC] >2.5 mM completely protected chymotrypsin against precipitation. This suggests that his40 reacts less readily with DEPC, and that chymotrypsin denaturation is caused by Hg(II) binding specifically to the his40 residue. Finally, we show that Hg(II)-histidine binding may trigger hemoglobin aggregation as well. Because of results with these two enzymes, we suggest that metal-histidine binding may be key to understanding all heavy metal-induced protein aggregation.