The C-terminal region of Trypanosoma cruzi MASPs is antigenic and secreted via exovesicles.

Trypanosoma cruzi is the etiological agent of Chagas disease, a neglected and emerging tropical disease, endemic to South America and present in non-endemic regions due to human migration. The MASP multigene family is specific to T. cruzi, accounting for 6% of the parasite's genome and plays a key role in immune evasion. A common feature of MASPs is the presence of two conserved regions: an N-terminal region codifying for signal peptide and a C-terminal (C-term) region, which potentially acts as GPI-addition signal peptide. Our aim was the analysis of the presence of an immune response against the MASP C-term region. We found that this region is highly conserved, released via exovesicles (EVs) and has an associated immune response as revealed by epitope affinity mapping, IFA and inhibition of the complement lysis assays. We also demonstrate the presence of a fast IgM response in Balb/c mice infected with T. cruzi. Our results reveal the presence of non-canonical secreted peptides in EVs, which can subsequently be exposed to the immune system with a potential role in evading immune system targets in the parasite

Indoor use of attractive toxic sugar bait in combination with long-lasting insecticidal net against pyrethroid-resistant Anopheles gambiae: an experimental hut trial in Mbé, central Côte d'Ivoire.

BACKGROUND: Indoor attractive toxic sugar bait (ATSB) has potential as a supplementary vector-control and resistance-management tool, offering an alternative mode of insecticide delivery to current core vector-control interventions, with potential to deliver novel insecticides. Given the high long-lasting insecticidal bed net (LLIN) coverage across Africa, it is crucial that the efficacy of indoor ATSB in combination with LLINs is established before it is considered for wider use in public health. METHODS: An experimental hut trial to evaluate the efficacy of indoor ATSB traps treated with 4% boric acid (BA ATSB) or 1% chlorfenapyr (CFP ATSB) in combination with untreated nets or LLINs (holed or intact), took place at the M'bé field station in central Côte d'Ivoire against pyrethroid resistant Anopheles gambiae sensu lato. RESULTS: The addition of ATSB to LLINs increased the mortality rates of wild pyrethroid-resistant An. gambiae from 19% with LLIN alone to 28% with added BA ATSB and to 39% with added CFP ATSB (p < 0.001). Anopheles gambiae mortality with combined ATSB and untreated net was similar to that of combined ATSB and LLIN regardless of which insecticide was used in the ATSB. The presence of holes in the LLIN did not significantly affect ATSB-induced An. gambiae mortality. Comparative tests against pyrethroid resistant and susceptible strains using oral application of ATSB treated with pyrethroid demonstrated 66% higher survival rate among pyrethroid-resistant mosquitoes. CONCLUSION: Indoor ATSB traps in combination with LLINs enhanced the control of pyrethroid-resistant An. gambiae. However, many host-seeking An. gambiae entering experimental huts with indoor ATSB exited into the verandah trap without sugar feeding when restricted from a host by a LLIN. Although ATSB has potential for making effective use of classes of insecticide otherwise unsuited to vector control, it does not exempt potential selection of resistance via this route

The radium legacy: Contaminated land and the committed effective dose from the ingestion of radium contaminated materials

The manufacture and use of radium in the early to mid-20th century within industrial, medicinal and recreational products have resulted in a large number of contaminated sites across a number of countries with notable examples in the USA and Europe. These sites, represent a significant number of unregulated sources of potential radiological exposure that have collectively and hitherto not been well characterised. In 2007, the Radioactive Contaminated Land (RCL) Regulations came into force in the UK, providing the statutory guidance for regulators to classify and deal with RCL. Here we report on results derived from digestion experiments to estimate committed effective dose, a key aspect of the RCL Regulations, from the ingestion of radium contaminated sources that can be found in the environment. This case study includes particles, clinker and artefacts that arise from past military activities on a site that was once an airfield at Dalgety Bay on the Firth of Forth, UK. Since 2011 the number of radium contaminated finds has increased by one order of magnitude on the foreshore areas of Dalgety Bay. The increase in finds may in large part be attributed to a change in monitoring practice. A subsample of sixty sources was selected, on the basis of their activity and dimensions, and subjected to digestion in simulated stomach and lower intestine solutions. The study demonstrated that more radium-226 (226Ra) and lead-210 (210Pb; driven by Polonium solubility) are dissolved from sources in artificial &lsquo;stomach' solutions compared with &lsquo;lower intestine' solutions. The combined &lsquo;gut' solubility for 226Ra and apparent 210Pb varied from less than 1% to up to 35% ICRP 72 conversion factors were used to convert the activities measured in solution to committed effective dose. A little over 10% of the sources tested dissolved sufficient radioactivity to result in 100 mSv committed effective dose to an infant. Using the solubility of 35% as a worst case, minimum source activities necessary to deliver 100 mSv to the full age range of users of the foreshore were estimated. All the estimated activities have been detected and recovered through routine monitoring

Using the Pneumatic method to estimate embolism resistance in species with long vessels: A commentary on the article “A comparison of five methods to assess embolism resistance in trees”

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordComparisons among methods are essential to validate plant traits measured across studies. However, a rigorous analysis is a complex task that needs to take into account not only the principle of the method and its correct use, but also inherent intraspecific trait variability, something we feel is not fully considered by Sergent et al. (2020). They compared the Bench dehydration, MicroCT, and Pneumatic methods using three long-vesseled species and found divergence among these methods. As a key finding, Sergent and colleagues reported unreliable estimates of Ψ50 for Olea europaea when using the Pneumatic method in a such long-vesseled species. Here, we tested this finding by measuring independently vulnerability curves for O. europaea. Our results reinforce the viability of the Pneumatic method to estimate embolism vulnerability in long-vesseled species, as already found by others. Briefly, we also discuss important procedures when using the Pneumatic method and encourage further experiments, as the only way to know better the limitations of available methods and improve our understanding about plant water relations.São Paulo Research Foundation (FAPESP)Royal SocietyNational Council for Scientific and Technological Development (CNPq, Brazil

Firm insoles effectively reduce hemolysis in runners during long distance running - a comparative study

<p>Abstract</p> <p>Background</p> <p>Shock absorbing insoles are effective in reducing the magnitude and rate of loading of peak impact forces generated at foot strike during running, whereas the foot impact force during running has been considered to be an important cause of intravascular hemolysis in long distance runners. Objective of this study was to evaluate the intravascular hemolysis during running and compare the effect of two different types of insoles (Soft and Firm) on hemolysis.</p> <p>Methods</p> <p>Twenty male long and middle distance runners volunteered to participate in this study. We selected two insoles (Soft and Firm) according to their hardness level (SHORE 'A' scale). Participants were randomly assigned to the soft insole (group 1) and firm insole (group 2) group with ten athletes in each group. Each athlete completed one hour of running at the calculated target heart rate (60-70%). Venous blood samples were collected before and immediately after running. We measured unconjucated bilirubin (mg/dl), lactate dehydrogenase (μ/ml), hemoglobin (g/l) and serum ferritin (ng/ml) as indicators of hemolysis.</p> <p>Results</p> <p>Our study revealed a significant increase in the mean values of unconjucated bilirubin (P < 0.05) while running with soft insoles indicating the occurrence of hemolysis in this group of athletes. Graphical analysis revealed an inverse relationship between hardness of insoles and hemolysis for the observed values.</p> <p>Conclusion</p> <p>Our results indicate that intravascular hemolysis occurs in athletes during long distance running and we conclude that addition of firm insoles effectively reduces the amount of hemolysis in runners compared to soft insoles.</p

Late cardiotoxicity after low dose of anthracycline therapy for acute lymphoblastic leukemia in childhood

Introduction Late cardiotoxicity is a known complication of anthracycline therapy but the long-term effects of low cumulative doses are not well documented. We studied late cardiotoxicity in survivors of childhood acute lymphoblastic leukemia (ALL) treated with low anthracycline doses 10 to 20 years earlier. Methods Seventy-seven ALL survivors who received a cumulative anthracycline dose <250 mg/m(2) and were at least 10 years after treatment were evaluated for signs of clinical heart failure. Cardiac function was assessed by echocardiography including tissue Doppler measurements of the septal mitral annulus in 37 ALL survivors 10.6-18.3 years (median 13.3 years) after anthracycline treatment with cumulative doses of 180 (n=19) or 240 mg/m(2) (n=18). The control group consisted of 30 healthy volunteers matched for age, sex, BSA, and BMI. Results No clinical relevant cardiotoxicity was found. Left ventricular shortening fraction (SF) was significantly reduced in male ALL survivors. Three of the 19 male ALL survivors had an SF below 30%. Male ALL survivors showed a significantly lower early filling velocity to atrial contraction velocity ratio but myocardial velocity during early filling was comparable between patients and controls. ALL survivors had a significantly longer isovolumetric relaxation time (IVRT). Thirty percent of the ALL survivors have an abnormal IVRT compared to the normal range of the controls. Conclusion and implications for cancer survivors At a median of 13.3 years after exposure to cumulative doses of anthracyclines of 180 or 240 mg/m(2), no clinical relevant cardiotoxicity was found but subclinical cardiac abnormalities were present in 30% of the patients

A phase I study of pemetrexed (LY231514) supplemented with folate and vitamin B12 in Japanese patients with solid tumours

The purpose of this study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of pemetrexed with folate and vitamin B12 supplementation (FA/VB12) in Japanese patients with solid tumours and to investigate the safety, efficacy, and pharmacokinetics of pemetrexed. Eligible patients had incurable solid tumours by standard treatments, a performance status 0–2, and adequate organ function. Pemetrexed from 300 to 1200 mg m−2 was administered as a 10-min infusion on day 1 of a 21-day cycle with FA/VB12. Totally, 31 patients were treated. Dose-limiting toxicities were alanine aminotransferase (ALT) elevation at 700 mg m−2, and infection and skin rash at 1200 mg m−2. The MTD/RD were determined to be 1200/1000 mg m−2, respectively. The most common grade 3/4 toxicities were neutropenia (grade (G) 3:29, G4:3%), leucopenia (G3:13, G4:3%), lympopenia (G3:13%) and ALT elevation (G3:13%). Pemetrexed pharmacokinetics in Japanese were not overtly different from those in western patients. Partial response was achieved for 5/23 evaluable patients (four with non-small cell lung cancer (NSCLC) and one with thymoma). The MTD/RD of pemetrexed were determined to be 1200/1000 mg m−2, respectively, that is, a higher RD than without FA/VB12 (500 mg m−2). Pemetrexed with FA/VB12 showed a tolerable toxicity profile and potent antitumour activity against NSCLC in this study