Immunoglobulin G Subclass-Specific Glycosylation Changes in Primary Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) was previously shown to be associated with glycosylation changes of total serum and total IgG proteins. However, as a majority of previous studies analyzed released glycan profiles, still little is known about IgG subclass-specific alterations in ovarian cancer. Hence, in this study, we investigated EOC-related glycosylation changes of the three most abundant IgG subclasses, namely, IgG1, IgG2 and IgG3 isolated from sera of 87 EOC patients and 74 age-matched healthy controls. In order to separate IgG2 and IgG3, we performed a two-step affinity purification employing Protein A and Protein G Sepharose. After tryptic digestion, IgG glycopeptides were enriched and measured by MALDI-TOF-MS. Finally, EOC-related glycosylation changes were monitored at the level of total agalactosylation, monogalactosylation, digalactosylation, sialylation, bisection and fucosylation, which were calculated separately for each IgG subclass. Interestingly, aside from an EOC-related increase in agalactosylation/decrease in monogalactosylation and digalactosylation observed in all IgG subclasses, some subclass-specific trends were detected. Glycosylation of IgG1 was found to be most strongly affected in EOC, as it exhibited the highest number of significant differences between healthy controls and EOC patients. Specifically, IgG1 was the only subclass that showed a significant decrease in sialylation and a significant increase in fucosylation in EOC patients. Interestingly, IgG2 and IgG3 that were often investigated collectively in previous studies, were found to have distinct glycosylation patterns. IgG3 displayed stronger EOC-related increase in agalactosylation/decrease in digalactosylation and was characterized by notably higher sialylation, which consequently decreased in EOC patients. In conclusion, our study indicates that IgG subclasses exhibit subtly distinct glycosylation patterns of EOC-related alterations and that IgG1 and IgG3 agalactosylation show the strongest association with CA125, the routine diagnostic marker. Additionally, our results show that simultaneous analyses of IgG2 and IgG3 might lead to wrong conclusions as these two subclasses exhibit noticeably different glycosylation phenotypes

Coronavirus Disease 2019-Related Alterations of Total and Anti-Spike IgG Glycosylation in Relation to Age and Anti-Spike IgG Titer

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been affecting the world since January 2020 and has caused millions of deaths. To gain a better insight into molecular changes underlying the COVID-19 disease, we investigated here the N-glycosylation of three immunoglobulin G (IgG) fractions isolated from plasma of 35 severe COVID-19 patients, namely total IgG(1), total IgG(2), and anti-Spike IgG, by means of MALDI-TOF-MS. All analyses were performed at the glycopeptide level to assure subclass- and site-specific information. For each COVID-19 patient, the analyses included three blood withdrawals at different time-points of hospitalization, which allowed profiling longitudinal alterations in IgG glycosylation. The COVID-19 patients presented altered IgG N-glycosylation profiles in all investigated IgG fractions. The most pronounced COVID-19-related changes were observed in the glycosylation profiles of antigen-specific anti-Spike IgG(1). Anti-Spike IgG(1) fucosylation and galactosylation showed the strongest variation during the disease course, with the difference in anti-Spike IgG(1) fucosylation being significantly correlated with patients' age. Decreases in anti-Spike IgG(1) galactosylation and sialylation in the course of the disease were found to be significantly correlated with the difference in anti-Spike IgG plasma concentration. The present findings suggest that patients' age and anti-S IgG abundance might influence IgG N-glycosylation alterations occurring in COVID-19

A cross-cultural perspective on psychological determinants of chronic fatigue syndrome: A comparison between a portuguese and a dutch patient sample

Background Few studies focus on cross-cultural differences in Chronic fatigue syndrome (CFS). Purpose This study aimed to (1) compare fatigue severity and impairment, somatic complaints, psychological distress, and quality of life (QoL) in a population of Portuguese and Dutch patients; (2) explore the differential contribution of behavioral and cognitive determinants of fatigue severity; and (3) investigate the relation between fatigue severity and somatic complaints on one hand and QoL on the other in both populations. Method Eighty-five female patients from Portugal (Mean age0 47.54) and 167 female CFS patients from The Netherlands (Mean age044.93) participated in the study. All participants were surveyed for demographic and clinical characteristics, fatigue severity, somatic symptoms, psychological distress, (physical and psychological) QoL, physical activity, behavior regulation patterns, and illness representations. Results Cross-cultural differences were found in relation to working status, duration of fatigue symptoms, psychological distress, somatic complaints, and psychological QoL. Although behavioral characteristics and illness representations were significantly associated with fatigue severity in both Portuguese and Dutch patients, there were important differences in the determinants of CFS. Moreover, higher levels of fatigue and severity of other somatic complaints were related to poor QoL. Conclusions These findings show cross-cultural similarities and differences in clinical characteristics and psychological determinants of CFS that are important in view of diagnosis and treatment

Aerosol size distribution and gaseous products from the oven-controlled combustion of straw materials

A number of controlled combustions have been carried out in the laboratory using samples of oats and barley straw collected in Spain in order to establish the characteristic particle spectra of these emissions. In addition, chemical compounds such as CO2, NO2 and NO and gravimetric variations have been registered during the combustion processes. For each combustible the burning phase has also been defined. Burning barley generates a higher number of particles in the fine mode (with a diameter of less than 0.5 μm) than oats (74% vs. 59%). The distributions of particles emitted during the flaming phase have been characterized, as well as during the previous and subsequent phases. The average geometric diameter reached its maximum during the flaming phase, with 0.53 ± 0.10 μm and 0.44 ± 0.04 μm for oats and barley, respectively. After the flaming phase, oat straw generates coarser particles than barley.The authors would like to thank the Institute of the Environment, Natural Resources and Biodiversity (IMARENAB) of the University of León and its Director, Antonio Morán, for the permission to use the technical equipment. We would also like to thank José Merino Ibáñez (RIP), the farmers of Quintanilla de Onsoña, Jose Luis Marcos, Antonio Calvo and María Carmen Gordaliza for their help throughout the whole field campaign. The authors are also in debt to Noelia Ramón for translating this paper into English.publishe

Are schoolchildren less infected if they have good knowledge about parasitic worms? A case study from rural Côte d'Ivoire

Background: Parasitic worms (helminths) are common infections in low- and middle-income countries. For most helminth species, school-aged children are at highest risk of infection and morbidity, such as impaired cognitive and physical development. Preventive chemotherapy is the current mainstay for helminthiases control. Sanitation improvement and hygiene-related education are important complementary strategies, which act by altering children’s behaviour. However, little is known about the effect of improved knowledge on the risk of helminth infection. The aim of this study was to assess the potential influence of knowledge that children acquired at home or in school, without any specific health education intervention, on helminth infections. Methods: In May 2014, we conducted a cross-sectional survey in western Côte d’Ivoire. A total of 2498 children, aged 9-12 years, were subjected to three consecutive stool examinations using duplicate Kato-Katz thick smears to determine infections with soil-transmitted helminths and Schistosoma mansoni. Additionally, children were interviewed to assess their knowledge about helminth infections. Four knowledge scores were constructed by factor analysis; one, reflecting general knowledge about helminths and three manifesting helminth species-specific knowledge. The effect of general and specific knowledge on children’s helminth infection status was determined using meta-analysis. Results: Children who scored high in the hookworm-specific knowledge were less likely to be infected with hookworm but no association was found for the other helminth species. Moreover, greater general knowledge was not associated with lower odds of being infected with any helminth species. Most of the children interviewed believed that the effect of preventive chemotherapy is permanent, and hence, re-treatment is not necessary. Conclusions: Specific knowledge about different types of helminths might not suffice to induce behavioural change which in turn reduces infection and reinfection with helminths. Health education interventions should strive to strengthen the perception of risk and to clarify the true benefit of preventive chemotherapy.publishersversionpublishe

Cost-effectiveness analysis alongside the inter-B-NHL ritux 2010 trial:rituximab in children and adolescents with B cell non-Hodgkin’s lymphoma

Objectives: The randomized controlled trial Inter-B-NHL ritux 2010 showed overall survival (OS) benefit and event-free survival (EFS) benefit with the addition of rituximab to standard Lymphomes Malins B (LMB) chemotherapy in children and adolescents with high-risk, mature B cell non-Hodgkin’s lymphoma. Our aim was to assess the cost-effectiveness of rituximab-chemotherapy versus chemotherapy alone in the French setting.Methods: We used a decision-analytic semi-Markov model with four health states and 1-month cycles. Resource use was prospectively collected in the Inter-B-NHL ritux 2010 trial (NCT01516580). Transition probabilities were assessed from patient-level data from the trial (n = 328). In the base case analysis, direct medical costs from the French National Insurance Scheme and life-years (LYs) were computed in both arms over a 3-year time horizon. Incremental net monetary benefit and cost-effectiveness acceptability curve were computed through a probabilistic sensitivity analysis. Deterministic sensitivity analysis and several sensitivity analyses on key assumptions were also conducted, including one exploratory analysis with quality-adjusted life years as the health outcome.Results: OS and EFS benefits shown in the Inter-B-NHL ritux 2010 trial translated into the model by rituximab-chemotherapy being the most effective and also the least expensive strategy over the chemotherapy strategy. The mean difference in LYs between arms was 0.13 [95% CI 0.02; 0.25], and the mean cost difference € − 3 710 [95% CI € − 17,877; € 10,525] in favor of rituximab-chemotherapy group. For a € 50,000 per LY willingness-to-pay threshold, the probability of the rituximab-chemotherapy strategy being cost-effective was 91.1%. All sensitivity analyses confirmed these findings.Conclusion: Adding rituximab to LMB chemotherapy in children and adolescents with high-risk mature B-cell non-Hodgkin's lymphoma is highly cost-effective in France.Trial registration: ClinicalTrials.gov identifier: NCT01516580

Experimental Tuberculosis in the Wistar Rat: A Model for Protective Immunity and Control of Infection

BACKGROUND: Despite the availability of many animal models for tuberculosis (TB) research, there still exists a need for better understanding of the quiescent stage of disease observed in many humans. Here, we explored the use of the Wistar rat model for the study of protective immunity and control of Mycobacterium tuberculosis (Mtb) infection. METHODOLOGY/PRINCIPAL FINDINGS: The kinetics of bacillary growth, evaluated by the colony stimulating assay (CFU) and the extent of lung pathology in Mtb infected Wistar rats were dependent on the virulence of the strains and the size of the infecting inoculums. Bacillary growth control was associated with induction of T helper type 1 (Th1) activation, the magnitude of which was also Mtb strain and dose dependent. Histopathology analysis of the infected lungs demonstrated the formation of well organized granulomas comprising epithelioid cells, multinucleated giant cells and foamy macrophages surrounded by large numbers of lymphocytes. The late stage subclinical form of disease was reactivated by immunosuppression leading to increased lung CFU. CONCLUSION: The Wistar rat is a valuable model for better understanding host-pathogen interactions that result in control of Mtb infection and potentially establishment of latent TB. These properties together with the ease of manipulation, relatively low cost and well established use of rats in toxicology and pharmacokinetic analyses make the rat a good animal model for TB drug discovery

The IARC perspective on cervical cancer screening

In May 2018, the World Health Organization (WHO) called for a global initiative to eliminate cervical cancer as a public health problem. To achieve this goal, global scale-up of effective vaccination against the human papillomavirus (HPV) as well as screening for and treatment of cervical cancer are required. Cervical cancer screening was evaluated in 2005 by the International Agency for Research on Cancer (IARC) Handbooks program,1 and a reevaluation was deemed to be timely given the major advances in the field since then. The new handbook provides updated evaluations of the effectiveness of screening methods, which were used as a basis for the update of the WHO Guideline for Screening and Treatment of Cervical Pre-cancer Lesions for Cervical Cancer Prevention.2 We convened an IARC Working Group of 27 scientists from 20 countries to assess the evidence on the current approaches to and technologies used in cervical cancer screening with the use of the newly updated Handbooks Preamble3 (Fig. 1) and Table 1).Fil: Bouvard, Véronique. International Agency For Research On Cancer; FranciaFil: Wentzensen, Nicolas. National Cancer Institute; Estados UnidosFil: Mackie, Anne. Public Health England; Reino UnidoFil: Berkhof, Johannes. University of Amsterdam; Países BajosFil: Brotherton, Julia. VCS Foundation; Australia. University of Melbourne; AustraliaFil: Giorgi Rossi, Paolo. Azienda Unità Sanitaria Locale Di Reggio Emilia; ItaliaFil: Kupets, Rachel. University of Toronto; CanadáFil: Smith, Robert. American Cancer Society; Estados UnidosFil: Arrossi, Silvina. Centro de Estudios de Estado y Sociedad; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bendahhou, Karima. Casablanca Cancer Registry; MarruecosFil: Canfell, Karen. The University Of Sydney; AustraliaFil: Chirenje, Z. Mike. University Of Zimbabwe; ZimbabueFil: Chung, Michael H.. University of Emory; Estados UnidosFil: del Pino, Marta. Hospital Clinico de Barcelona; EspañaFil: de Sanjosé, Silvia. Program for Appropriate Technology in Health; Estados UnidosFil: Elfström, Miriam. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Franco, Eduardo L.. McGill University; CanadáFil: Hamashima, Chisato. Teikyo University; JapónFil: Hamers, Françoise F.. French National Public Health Agency; FranciaFil: Herrington, C. Simon. University of Edinburgh; Reino UnidoFil: Murillo, Raúl. Hospital Universitario San Ignacio; ColombiaFil: Sangrajrang, Suleeporn. National Cancer Institute; TailandiaFil: Sankaranarayanan, Rengaswamy. Research Triangle Institute; Estados UnidosFil: Saraiya, Mona. Centers for Disease Control and Prevention; Estados UnidosFil: Schiffman, Mark. National Cancer Institute; Estados UnidosFil: Zhao, Fanghui. Chinese Academy of Medical Sciences & Peking Union Medical College; ChinaFil: Arbyn, Marc. Sciensano; BélgicaFil: Prendiville, Walter. International Agency For Research On Cancer; FranciaFil: Indave Ruiz, Blanca I.. International Agency For Research On Cancer; FranciaFil: Mosquera Metcalfe, Isabel. International Agency For Research On Cancer; FranciaFil: Lauby Secretan, Béatrice. International Agency For Research On Cancer; Franci

Are schoolchildren less infected if they have good knowledge about parasitic worms? A case study from rural Côte d'Ivoire

Parasitic worms (helminths) are common infections in low- and middle-income countries. For most helminth species, school-aged children are at highest risk of infection and morbidity, such as impaired cognitive and physical development. Preventive chemotherapy is the current mainstay for helminthiases control. Sanitation improvement and hygiene-related education are important complementary strategies, which act by altering children's behaviour. However, little is known about the effect of improved knowledge on the risk of helminth infection. The aim of this study was to assess the potential influence of knowledge that children acquired at home or in school, without any specific health education intervention, on helminth infections.; In May 2014, we conducted a cross-sectional survey in western Côte d'Ivoire. A total of 2498 children, aged 9-12 years, were subjected to three consecutive stool examinations using duplicate Kato-Katz thick smears to determine infections with soil-transmitted helminths and Schistosoma mansoni. Additionally, children were interviewed to assess their knowledge about helminth infections. Four knowledge scores were constructed by factor analysis; one, reflecting general knowledge about helminths and three manifesting helminth species-specific knowledge. The effect of general and specific knowledge on children's helminth infection status was determined using meta-analysis.; Children who scored high in the hookworm-specific knowledge were less likely to be infected with hookworm but no association was found for the other helminth species. Moreover, greater general knowledge was not associated with lower odds of being infected with any helminth species. Most of the children interviewed believed that the effect of preventive chemotherapy is permanent, and hence, re-treatment is not necessary.; Specific knowledge about different types of helminths might not suffice to induce behavioural change which in turn reduces infection and reinfection with helminths. Health education interventions should strive to strengthen the perception of risk and to clarify the true benefit of preventive chemotherapy

A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS)

Objectives Treat-to-target recommendations have identified 'remission' as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE. Methods An international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%. Results The task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions: 1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by . (reference to symptoms, signs, routine labs). 2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment. 3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics. The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life. Conclusions The work of this international task force provides a framework for testing different definitions of remission against long-term outcomes