Indirect Effects of Oral Tolerance Inhibit Pulmonary Granulomas to Schistosoma mansoni Eggs

Parenteral injection of tolerated proteins into orally tolerant mice inhibits the initiation of immunological responses to unrelated proteins and blocks severe chronic inflammatory reactions of immunological origin, such as autoimmune reactions. This inhibitory effect which we have called “indirect effects of oral tolerance” is also known as “bystander suppression.” Herein, we show that i.p. injection of OVA + Al(OH)3 minutes before i.v. injection of Schistosoma mansoni eggs into OVA tolerant mice blocked the increase of pulmonary granulomas. In addition, the expression of ICAM-1 in lung parenchyma in areas outside the granulomas of OVA-orally tolerant mice was significantly reduced. However, at day 18 after granuloma induction there was no difference in immunofluorescency intensity to CD3, CD4, F4/80, andα-SMA per granuloma area of tolerant and control groups. Reduction of granulomas by reexposure to orally tolerated proteins was not correlated with a shift in Th-1/Th-2 cytokines in serum or lung tissue extract

Outcrossing rate in olive assessed by microsatellite and inter simple sequence repeat (ISSR) markers

Olive is known to be an allogamous species. The aim of this study was to estimate the magnitude of cross-pollination rate using microsatellite simple sequence repeats (SSR) and inter simple sequence repeats (ISSR) molecular markers in olive genotypes. The DNA from maternal plants and 23 progenies of two different accessions, Ascolano USA and MGS GRAP541 were extracted and screened with two microsatellite and ten ISSR markers. The outcrossing rate and other related parameters were analyzed using the MLTR application. The set of estimates, individually and collectively, support the hypothesis of frequent allogamy in both olive genotypes evaluated, with high rates of outcrossing in both markers.Keywords: Olea europaea L., outcrossing rate, zygotic embryos, mating system, molecular marker

Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study

IntroductionSARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators.MethodsA sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array.ResultsIn the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester.Discussion and conclusionFrom an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Efeitos inibitórios da exposição parenteral a antígenos tolerados sobre a reação granulomatosa a ovos de Schistosoma mansoni

Exportado OPUSMade available in DSpace on 2019-08-14T20:45:55Z (GMT). No. of bitstreams: 1 tese_de_doutorado_g._magela.pdf: 4319438 bytes, checksum: 277d73b2898844e690ad8dd69d3bf0d1 (MD5) Previous issue date: 24A injeção parenteral de proteínas previamente administradas por via oral inibe o desencadeamento de respostas imunes à proteínas não especificamente relacionadas e bloqueia reações inflamatórias de origem imunológica, tais como doenças auto-imunes. Este efeito inibitório que denominamos efeitos indiretos da tolerância oral também é conhecido como bystander suppression. Neste trabalho mostrou-se que a injeção i.p. de OVA+Al(OH)3 minutos antes da injeção i.v. de ovos de Schistosoma mansoni em camundongos tolerantes a OVA bloqueia a formação de granulomas pulmonares. Demonstrou-se que há menor expressão de ICAM-1 no parênquima pulmonar adjacente aos granulomas de camundongos tolerantes à OVA e imunizados com OVA+Al(OH)3 em comparação com grupos controles. Aos 18 dias após a inoculação dos ovos, não foram observadas diferenças na intensidade de expressão dea CD3, CD4, F4/80 e -SMA nos granulomas de grupos tolerante e controles. A redução dos granulomas após a re-exposição parenteral de proteínas toleradas não foi correlacionada com alterações nos níveis de citocinas Th1/Th2 presentes no soro ou em extratos pulmonaresParenteral injection of tolerated proteins into orally tolerant mice inhibits the initiation of immunological responses to unrelated proteins and blocks severe chronic inflammatory reactions of immunological origin, such as autoimmune reactions. This inhibitory effect wich we have called indirect effects of oral tolerance is also known as bystander suppression. Herein, we show that i.p. injection of OVA + Al(OH)3 minutes before i.v. injection of Schistosoma mansoni eggs into OVA tolerant mice blocked the increase of pulmonary granulomas. In addition, the expression of ICAM-1 in lung parenchyma in areas outside the granulomas of OVA orally tolerant mice was significantly reduced. However, at day 18 after granuloma induction there was no difference in immunofluorescency intensity to CD3, CD4, F4/80, and -SMA per granuloma area of tolerant and control groups. Reduction of granulomas by reexposure to orally tolerated proteins was not correlated with a shift in Th-1/Th-2 cytokines in serum or lung extrac

Impact of compression therapy using Unna's boot on the self-esteem of patients with venous leg ulcers

Objective: To assess self-esteem in patients with venous leg ulcers treated with Unna's boot.Method: A descriptive, analytic, clinical study was conducted from June 2010 to May 2011 in an outpatient wound care clinic in Sao Paulo, Brazil. Patients of both sexes, aged >= 18 years, who had had a venous leg ulcer for more than one year and a Doppler ankle brachial index ranging from 0.8-1.0 were consecutively selected for inclusion. Patients were treated with wound dressings and Unna's boot. Self-esteem was assessed using the Brazilian version of the Rosenberg Self-Esteem Scale (RSE) at inclusion (baseline) and after 4, 8, and 12 months of compression therapy using Unna's boot. The scale is reverse-scored; thus lower scores indicate higher levels of self-esteem.Results: The patients showed a slight but significant improvement in self-esteem after 4 months of treatment (mean RSE score= 17.12) compared with baseline (mean RSE score= 24.90). However, a marked and significant improvement in self-esteem was observed after 8 months (mean RSE score=7.40) and 12 months (mean RSE score=2.10) of compression therapy using Unna's boot.Conclusion: Patients with venous leg ulcers treated with Unna's boot for 12 months showed a significant improvement in self-esteem.Declaration of interest: All authors declare that no competing financial interests exist. There was no external funding for this study.Sapucai Valley Univ UNIVAS, Pouso Alegre, MG, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilWeb of Scienc

The impact of compression therapy with Unna's boot on the functional status of VLU patients

Objective: To assess disability in patients with venous leg ulcers treated with compression therapy with Unna's boot.Method: A descriptive analytic case control study was conducted from June 2010 to May 2011 in an outpatient wound care clinic in interior Brazil. Fifty patients of both sexes, aged 18 years or above, who had had a venous leg ulcer for more than 1 year and a Doppler ankle-brachial index of 0.8-1.0 were selected for the study. Patients were treated with wound dressings and Unna's boot. Disability was assessed using the 20-item Stanford Health Assessment Disability Scale (HAQ-20). Statistical analysis was performed using the Student's t-test, the Kruskal-Wallis test and the chi-square test of independence, all at a significance level of 0.05 (p<0.05).Results: The mean overall HAQ score at inclusion (baseline) was 2.98, indicating impaired functional capacity. After 8 and 12 months of compression treatment with Unna's boot, the mean overall HAQ scores were 1.35 and 1.0, respectively, indicating good functional capacity.Conclusion: Patients with venous leg ulcer reported severe difficulty or serious disability in their daily functioning at baseline; after 8 months of treatment with Unna's boot, these patients were able to perform activities of daily living.Univ Vale do Sapucai UNIVAS, Pouso Alegre, MG, BrazilUniv Fed Sao Paulo UNIFESP, Div Plast Surg, Sao Paulo, BrazilUniv Fed Sao Paulo UNIFESP, Div Plast Surg, Sao Paulo, BrazilWeb of Scienc