"Antarctic yeasts as a source of L-asparaginase: Characterization of a glutaminase-activity free L-asparaginase from psychrotolerant yeast Leucosporidium scottii L115"

"Microorganisms from extreme environments, such as the Antarctic ecosystems, have a great potential to produce enzymes with novel characteristics. Within this context, L-asparaginase (ASNase) obtained from yeast species has been poorly studied. In this study, yeasts isolated from samples collected at Admiralty Bay (King George Island, Antarctica) were tested to produce ASNase. From an initial screening of 40 strains, belonging to 13 different species, Leucosporidium scottii L115 produced an ASNase activity (LsASNase activity: 6.24 U g-1 of dry cell weight) with the lowest glutaminase activity. The LsASNase was purified 227-fold, with a specific activity of 137.01 U mg-1 at 37 ◦C, without glutaminase activity. Moreover, the maximum enzyme activity was observed at pH 7.5 and at a temperature of 55 ◦C. The enzyme is a multimer of 462 kDa, presenting a single band of 53 kDa molecular mass in reduced conditions; after PGNase F treatment, a single band of 45 kDa was observed. The enzymatic kinetic evaluation revealed an allosteric regulation of the enzyme and the kinetic parameters were determined at 37 ◦C, pH 7.0 as substrate affinity constant, K0.5 = 233 μM, kcat = 54.7 s − 1 and Hill coefficient, nH = 1.52, demonstrating positive cooperativity by the enzyme and the substrate. This is the first study to report L. scottii as a source of glutaminase-activity free L-asparaginase, an acute lymphoblastic leukemia drug feature suitable for the treatment of asparagine synthetase negative cancer cells.

Primary Angioplasty in a Catastrophic Presentation: Acute Left Main Coronary Total Occlusion—The ATOLMA Registry

Objectives. To determine the outcome predictors of in-hospital mortality in acute total occlusion of the left main coronary artery (ATOLMA) patients referred to emergent angioplasty and to describe the clinical presentation and the long-term outcome of these patients.Background. ATOLMA is an uncommon angiographic finding that usually leads to a catastrophic presentation. Limited and inconsistent data have been previously reported regarding true ATOLMA, yet comprehensive knowledge remains scarce.Methods. This is a multicenter retrospective cohort that includes patients presenting with myocardial infarction due to a confirmed ATOLMA who underwent emergency percutaneous coronary intervention (PCI).Results. In the period of the study, 7930 emergent PCI were performed in the five participating centers, and 46 of them had a true ATOLMA (0.58%). At admission, cardiogenic shock was present in 89% of patients, and cardiopulmonary resuscitation was required in 67.4%. All the patients had right dominance. Angiographic success was achieved in 80.4% of the procedures, 13 patients (28.2%) died during the catheterization, and the in-hospital mortality rate was 58.6% (27/46). At one-year and at the final follow-up, 18 patients (39%) were alive, including four cases successfully transplanted. Multivariate analysis showed that postprocedural TIMI flow was the only independent predictor of in-hospital mortality (OR 0.23, (95% CI 0.1-0.36),p<0.001).Conclusions. Our study confirms that the clinical presentation of ATOLMA is catastrophic, presenting a high in-hospital mortality rate; nevertheless, primary angioplasty in this setting is feasible. Postprocedural TIMI flow resulted as the only independent predictor of in-hospital mortality. In-hospital survivors presented an encouraging outcome. ATOLMA and left dominance could be incompatible with life

Sex differences in treatment strategy for coronary artery aneurysms: Insights from the international Coronary Artery Aneurysm Registry

INTRODUCTION: Sex disparities exist in coronary artery disease (CAD) in terms of risk profile, clinical management and outcome. It is unclear if differences are also present in coronary aneurysms, a rare variant of CAD. METHODS: Patients were selected from the international Coronary Artery Aneurysm Registry (CAAR; ClinicalTrials.gov: NCT02563626), and differences between groups were analysed according to sex. The CAAR database is a prospective multicentre registry of 1565 patients with coronary aneurysms (336 females). Kaplan-Meier method was used for event-free survival analysis for death, major adverse cardiac events (MACE: composite endpoint of death, heart failure and acute coronary syndrome) and bleeding. RESULTS: Female patients were older, were more often hypertensive and less frequently smoker. They were treated conservatively more often compared to male patients and received significantly less frequently aspirin (92% vs 88%, p = 0.002) or dual antiplatelet therapy (DAPT) (67% vs 58%, p = 0.001) at discharge. Median DAPT duration was also shorter (3 vs 9 months, p = 0.001). Kaplan-Meier analysis revealed no sex differences in death, MACE or bleeding during a median follow-up duration of 37 months, although male patients did experience acute coronary syndrome (ACS) more often during follow-up (15% vs 10%, p = 0.015). CONCLUSIONS: These CAAR findings showed a comparable high-risk cardiovascular risk profile for both sexes. Female patients were treated conservatively more often and received DAPT less often at discharge, with a shorter DAPT duration. ACS was more prevalent among male patients; however, overall clinical outcome was not different between male and female patients during follow-up

White privilege, empathy and alterity in higher education : Teaching about race and racism in the sociology of PE and sport

In this chapter we provide a reflexive account on personal experiences teaching in HE in order to consider the extent to which our status as white HE practitioners reinforces and/or undermines white privilege in HE. As lecturers teaching within the discipline of sociology in physical education (PE) and sport contexts, we question whether our delivery of lectures on race and racism effectively challenges racialised discourses and encourages social action within our field. Despite the fact that the undergraduate programmes we work on incorporate lectures on race and ethnicity as a crucial part of the curriculum, these sessions have rarely been delivered by black and minority ethnic (BME) academics. We therefore consider whether our practice can provide a critical pedagogic voice, or if it simply provides a platform for white academics to unconsciously reinforce the institutional whiteness of HE. In particular, we reflect upon the possibility for white academics to empathise with the racialised social experiences of BME students in our cohorts, and the potential risk that our practice simply offers tokenistic discussion of race which reinforce the current forms of inequality and white privilege, whilst violating the alterity of our students

Cyclooxygenase-2 and prostaglandin E<inf>2</inf> signaling through prostaglandin receptor EP- 2 favor the development of myocarditis during acute trypanosoma cruzi infection

Inflammation plays an important role in the pathophysiology of Chagas disease, caused by Trypanosoma cruzi. Prostanoids are regulators of homeostasis and inflammation and are produced mainly by myeloid cells, being cyclooxygenases, COX-1 and COX-2, the key enzymes in their biosynthesis from arachidonic acid (AA). Here, we have investigated the expression of enzymes involved in AA metabolism during T. cruzi infection. Our results show an increase in the expression of several of these enzymes in acute T. cruzi infected heart. Interestingly, COX-2 was expressed by CD68+ myeloid heart-infiltrating cells. In addition, infiltrating myeloid CD11b+Ly6G- cells purified from infected heart tissue express COX-2 and produce prostaglandin E2 (PGE2) ex vivo. T. cruzi infections in COX-2 or PGE2- dependent prostaglandin receptor EP-2 deficient mice indicate that both, COX-2 and EP-2 signaling contribute significantly to the heart leukocyte infiltration and to the release of chemokines and inflammatory cytokines in the heart of T. cruzi infected mice. In conclusion, COX-2 plays a detrimental role in acute Chagas disease myocarditis and points to COX-2 as a potential target for immune intervention.This work was supported by (NG) grants from “Fondo de Investigaciones Sanitarias” (PS09/00538 and PI12/00289); “Universidad Autónoma de Madrid” and “Comunidad de Madrid” (CC08-UAM/SAL-4440/08); by (MF) grants from “Ministerio de Ciencia e Innovación” (SAF2010-17833); “Red de Investigación de Centros de Enfermedades Tropicales” (RICET RD12/0018/0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet); AECID Cooperation with Argentine (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD- 2332) and “Fundación Ramón Areces”. NAG was recipient of a ISCIII Ph.D. fellowship financed by the Spanish “Ministerio de Sanidad”. CCM and HC were recipients of contracts from SAF2010-17833 and PI060388, respectively.Peer Reviewe

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised