Novel expression of Haemonchus contortus vaccine candidate aminopeptidase H11 using the free-living nematode Caenorhabditis elegans

With the problem of parasitic nematode drug resistance increasing, vaccine development offers an alternative sustainable control approach. For some parasitic nematodes, native extracts enriched for specific proteins are highly protective. However, recombinant forms of these proteins have failed to replicate this protection. This is thought to be due to differences in glycosylation and/or conformation between native and recombinant proteins. We have exploited the free-living nematode Caenorhabditis elegans to examine its suitability as an alternative system for recombinant expression of parasitic nematode vaccine candidates. We focussed on Haemonchus contortus aminopeptidase H11 glycoprotein, which is enriched in a gut membrane fraction capable of inducing significant protection against this important ovine gastrointestinal nematode. We show that H. contortus H11 expressed in C. elegans is enzymatically active and MALDI mass spectrometry identifies similar di- and tri-fucosylated structures to those on native H11, with fucose at the 3- and/or 6-positions of the proximal GlcNAc. Some glycan structural differences were observed, such as lack of LDNF. Serum antibody to native H11 binds to C. elegans recombinant H11 and most of the antibody to rH11 or native H11 is directed to glycan moieties. Despite these similarities, no reduction in worm burden or faecal egg count was observed following immunisation of sheep with C. elegans-expressed recombinant H11 protein. The findings suggest that the di- and tri-fucosylated N-glycans expressed on rH11 do not contribute to the protective effect of H11 and that additional components present in native H11-enriched extract are likely required for enhancing the antibody response necessary for protection

Recognition of hypovolemic shock: using base deficit to think outside of the ATLS box

Base deficit has frequently been utilized as an informal adjunct in the initial evaluation of trauma patients to assess the extent of their physiologic derangements. However, the current Advanced Trauma Life Support (ATLS) classification system for hypovolemic shock does not include base-deficit measurements and relies primarily on alterations in vital signs (heart rate, systolic blood pressure) and mental status (Glasgow Coma Scale) to estimate blood loss. The authors of this paper propose that the current ATLS system may not accurately reflect the degree of hypovolemic shock in many patients and that base-deficit measurements should be used in its place. The proposed system showed a greater correlation with transfusion requirements, need for massive transfusion, and mortality when compared with the ATLS classification system. Based on these findings, base-deficit measurement should be strongly considered during the initial trauma evaluation to identify the presence of hypovolemic shock and to guide blood product administration

Comparison of a Novel Curvilinear Approach to Conventional Rectilinear Approach for Prostate Seed Implant

Purpose: To evaluate dosimetric benefit of curvilinear distribution of seeds for low-dose-rate (LDR) prostate brachytherapy with I-125 isotopes. American Association of Physicists in Medicine (AAPM) 52nd Annual Meeting July 18-22, Philadelphia, P

The surgical workforce shortage and successes in retaining surgical trainees in Ethiopia: a professional survey

BACKGROUND: Medical workforce shortages represent a major challenge in low- and middle-income countries, including those in Africa. Despite this, there is a dearth of information regarding the location and practice of African surgeons following completion of their training. In response to the call by the WHO Global Code of Practice on the International Recruitment of Health Personnel for a sound evidence base regarding patterns of practice and migration of the health workforce, this study describes the current place of residence, practice and setting of Ethiopian surgical residency graduates since commencement of their surgical training in Ethiopia or in Cuba. METHODS: This study presents data from a survey of all Ethiopian surgical residency training graduates since the programme’s inception in 1985. RESULTS: A total of 348 Ethiopians had undergone surgical training in Ethiopia or Cuba since 1985; data for 327 (94.0 %) of these surgeons were collected and included in the study. The findings indicated that 75.8 % of graduates continued to practice in Ethiopia, with 80.9 % of these practicing in the public sector. Additionally, recent graduates were more likely to remain in Ethiopia and work within the public sector. The average total number of surgeons per million inhabitants in Ethiopia was approximately three and 48.0 % of Ethiopian surgeons practiced in Addis Ababa. CONCLUSIONS: Ethiopian surgeons are increasingly likely to remain in Ethiopia and to practice in the public sector. Nevertheless, Ethiopia continues to suffer from a drastic surgical workforce shortage that must be addressed through increased training capacity and strategies to combat emigration and attrition

From livelihoods to leisure and back: refugee ‘self-reliance’ as collective practices in Lebanon, India and Greece

Over the last two decades, leading humanitarian agencies in the Global North have increasingly promoted a policy of self-reliance, understood as making individual refugees financially independent from aid assistance through livelihood programmes. However, individual economic autonomy offers an incomplete picture of refugee well-being. Based on fieldwork conducted over 2017 in Halba (Lebanon), Delhi (India) and Thessaloniki (Greece), this multi-site study shows that non-camp refugees build on collective strategies at household, social network and community levels in efforts to develop mechanisms of survival and enfranchisement. These strategies include social and leisure activities as well as income-generating activities which are often organised compartmentally in humanitarian programming. We argue that while leisure and social mingling alone cannot ensure economic sustainability, they are fundamental dimensions of self-reliance as seen by refugees and should therefore be systematically included in livelihood programming. “It is on a living tree that the vine grows” (Ghanaian proverb teaching support, growth and interdependence on one another within the community)

Effects of EGFR Expression on Anti-tumor Efficacy of Vandetanib or Cediranib Combined with Radiotherapy (RT) in U87 Human Glioblastoma (GBM) Xenografts

Introduction: Vandetanib is a receptor tyrosine kinase inhibitor (RTKI) with activity against vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR). Cediranib is a highly potent VEGF RTKI that inhibits all three VEGF receptors. In this study we investigated the effect of exogenous overexpression of EGFR on sensitivity of human GBM U87 xenografts to vandetanib or cediranib, alone or in combination with RT. American Association for Cancer Research (AACR) 101st Annual Meeting April 17-21, Washington, DC