Insights on the Evolution of Prolyl 3-Hydroxylation Sites from Comparative Analysis of Chicken and Xenopus Fibrillar Collagens

Recessive mutations that prevent 3-hydroxyproline formation in type I collagen have been shown to cause forms of osteogenesis imperfecta. In mammals, all A-clade collagen chains with a GPP sequence at the A1 site (P986), except α1(III), have 3Hyp at residue P986. Available avian, amphibian and reptilian type III collagen sequences from the genomic database (Ensembl) all differ in sequence motif from mammals at the A1 site. This suggests a potential evolutionary distinction in prolyl 3-hydroxylation between mammals and earlier vertebrates. Using peptide mass spectrometry, we confirmed that this 3Hyp site is fully occupied in α1(III) from an amphibian, Xenopus laevis, as it is in chicken. A thorough characterization of all predicted 3Hyp sites in collagen types I, II, III and V from chicken and xenopus revealed further differences in the pattern of occupancy of the A3 site (P707). In mammals only α2(I) and α2(V) chains had any 3Hyp at the A3 site, whereas in chicken all α-chains except α1(III) had A3 at least partially 3-hydroxylated. The A3 site was also partially 3-hydroxylated in xenopus α1(I). Minor differences in covalent cross-linking between chicken, xenopus and mammal type I and III collagens were also found as a potential index of evolving functional differences. The function of 3Hyp is still unknown but observed differences in site occupancy during vertebrate evolution are likely to give important clues

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Outcome and hospitalization costs after aneurysmal subarachnoid hemorrhage : a single center retrospective analysis

Aneurysmal subarachnoid hemorrhage (aSAH) has a highly variable clinical outcome. Extended ICU and hospital stay often result in increased healthcare related costs. This study aimed to examine the relationship between aSAH severity, hospital costs and functional outcome in patients who required urgent or semi-urgent endovascular repair. Patients treated with endovascular repair after experiencing aSAH from January 2017 until September 2018 were included in this retrospective single center study. aSAH severity upon admission was classified by the World Federation of Neurosurgical Societies (WFNS) grade, dichotomized into WFNS grade 1-2, 'low grade aSAH' and WFNS grade 3-5, 'high grade aSAH'. Functional outcome was assessed at ICU discharge and 1 year post aSAH by utilizing the modified Rankin Scale (mRS) and converted to quality adjusted life years (QALY) for the latter time point. Healthcare related costs during index hospital stay were analyzed. A total of 69 patients were included with 44 (63,8%) suffering from low grade aSAH and 25 (36,2%) from high grade aSAH. Median utility scores at 1 year were 0,93 (IQR 0,83-0,93) for low grade aSAH and 0,42 (IQR 0-0,83) for high grade aSAH (p<0,001). Mean total costs were 56.150 euro (IQR 25.572-62.060) in high grade and 26.288 euro (IQR 18.893-29.993) in low grade aSAH (p=0,003). Cost per 0.1 QALY gain in high grade aSAH was 13.233 euro (IQR 2.803-23.072) and higher than in low grade aSAH 3.497 euro (IQR 2.200-3.344) (p=0,027). Short term healthcare related costs strongly depend on aSAH severity. ICU stay and ICU related complications were important cost driving factors. High grade aSAH is also accompanied by lower functional outcomes at 1 year and decreased cost-effectiveness in comparison to low grade aSAH

A Novel Framework for Technological Evolution within Product Architecture

Part 1: Sustainable ProductionInternational audienceNowadays, products are increasingly complex mostly in the area of high value-added products such as airplanes, oil rigs, digger or central power generation. More generally, these products are more complex due to successive and concatenation of innovations introductions while products constraints needs a capitalization of all developed technologies. This paper introduces a novel framework for technological evolution/introduction within product architecture in order to assess and manage product family and modular architecture to personalize and customize products. This framework is based on a medical analogy to walk through customer need recognition, product portfolio, and new technological introduction in all product lifecycle. To be proactive, this challenge highlight the need to capitalize knowledge and lesson learned on the past, present and future of the product architecture and technology used in today’s products based on innovative processes. More than one part, a technology is characterized by resources needed by this artifact in order to answer to an added function, new requirements, or added services. So a methodology will be proposed to tackle this challenge to be innovative in product design

Fungal Biotechnology in Space: Why and How?

Fungi have been companions of mankind for millennia. Mushrooms inspired our eating culture, and yeasts and filamentous fungi were developed into highly efficient cell factories during the last 100 years to produce many products utilized in different industries worldwide. What more is to come in the next 100 years? We propose here that fungi can become important cell factories for life in space, especially regarding the filamentous fungus Aspergillus niger as the cutting-edge must-have for space travel in the twenty-first century and beyond. First, it is one of the most robust and efficient production systems used nowadays in industrial biotechnology. Second, it is a multipurpose cell factory that produces a diverse range of organic acids, proteins, enzymes and natural products. And third, it is a common fungal isolate of the International Space Station. A. niger could thus become an essential companion of astronauts for the autonomous production of food, enzymes and antibiotics during space travel. What needs to be done to achieve these visionary goals? In this chapter, we will discuss the opportunities of A. niger as a cell factory spanning from Earth to space. We summarize the current state of the art of A. niger biotechnology on Earth and discuss the general tools and technologies still in need of development to take a new step for mankind: space biotechnology