Influence of the HLA-DQB1*0201 allele on the immune response in a Schistosoma mansoni infection

We previously reported the association of the major histocompatibility complex class II HLA-DQB1*0201 allele with hepatosplenic schistosomiasis. The aim of this study was to evaluate the cytokine responses of peripheral blood mononuclear cells (PBMCs) and the serum levels of immunoglobulin isotypes. The study population was selected from a schistosomiasis endemic area. No significant differences in cytokine profiles were detected in PBMCs stimulated with Schistosoma mansoni soluble egg antigen (SEA), regardless of the subjects DQB1*0201 genotype or infection status. However, previously infected DQB1*0201 positive individuals had significantly lower levels of IgG4 compared to DQB1*0201 negative individuals (P<0.05).     

Multicentre phase III trial on fludarabine, cytarabine (Ara-C), and idarubicin versus idarubicin, Ara-C and etoposide for induction treatment of younger, newly diagnosed acute myeloid leukaemia patients

Fludarabine plus cytarabine (Ara-C) and idarubicin (FLAI) is an effective and well-tolerated induction regimen for the treatment of acute myeloid leukaemia (AML). This phase III trial compared the efficacy and toxicity of FLAI versus idarubicin plus Ara-C and etoposide (ICE) in 112 newly diagnosed AML patients <60 years. Fifty-seven patients received FLAI, as the first induction-remission course, and 55 patients received ICE. Post-induction treatment consisted of high-dose Ara-C (HDAC). After HDAC, patients in complete remission (CR) received a second consolidation course (mitoxantrone, etoposide, Ara-C) and autologous stem cell transplantation (auto-SCT) or allogeneic (allo)-SCT, according to the age, disease risk and donor availability. After a single induction course, CR rate was 74% in the FLAI arm and 51% in the ICE arm (P = 0.01), while death during induction was 2% and 9% respectively. Both haematological (P = 0.002) and non-haematological (P = 0.0001) toxicities, especially gastrointestinal (i.e. nausea, vomiting, mucositis and diarrhoea), were significantly lower in FLAI arm. In both arms, relapses were more frequent in patients who were not submitted to allo-SCT. After a median follow-up of 17 months, 30% and 38% of the patients are in continuous CR in FLAI and ICE arm respectively. Our prospective randomised study confirmed the anti-leukaemic effect and the low toxic profile of FLAI as induction treatment for newly diagnosed AML patients.     

Comparative analysis of non-adherence to medication treatment for systemic arterial hypertension in urban and rural populations

OBJECTIVE:

to evaluate the indexes and the main factors associated with non-adherence to medication treatment for systemic arterial hypertension between urban and rural areas.

METHOD:

analytical study based on an epidemiological survey with a sample of 247 hypertensive residents of rural and urban areas, with application of a socio-demographic and economic questionnaire, and treatment adherence assessment. The Pearson''s Chi-square test was used and the odds ratio (OD) was calculated to analyze the factors related to non-adherence.

RESULTS:

the prevalence of non-adherence was 61.9% and it was higher in urban areas (63.4%). Factors significantly associated with non-adherence were: male gender (OR=1.95; 95% CI 1.08-3.50), age 20-59 years old (OR=2.51; 95% CI 1.44-4.39), low economic status (OR=1.95; 95% CI 1.09-3.47), alcohol consumption (OR=5.92, 95% CI 1.73-20.21), short time of hypertension diagnosis (OR=3.07; 95% CI 1.35-6.96) and not attending the health service for routine consultations (OR=2.45; 1.35-4.42).

CONCLUSION:

the socio-demographic/economic characteristics, lifestyle habits and how to relate to health services were the factors that presented association with non-adherence regardless of the place of residence.     

NADPH oxidase and enhanced superoxide generation in intrauterine undernourished rats: involvement of the renin-angiotensin system

OBJECTIVE: We previously reported that intrauterine undernutrition increased the oxidative stress by decreasing superoxide dismutase activity. In the present study, we tested whether NADPH oxidase, xanthine oxidase, cyclooxygenase or nitric oxide synthase are responsible for the increased O(2)(-) generation observed in rats submitted to intrauterine undernutrition. In addition, we investigated the effect of angiotensin II (ANG II) on O(2)(-) production via activation of NADPH oxidase. METHODS: Female pregnant Wistar rats were fed either normal or 50% of the normal intake diets, during the whole gestational period. At 16 weeks of age, the rats were used for the study of intravital fluorescence microscopy; microvascular reactivity, local ANG II concentration and AT(1), p22(phox) and gp91(phox) gene expression. In this study only the male offspring was used. RESULTS: Treatment of mesenteric arterioles with the xanthine oxidase inhibitor oxypurinol, the nitric oxide synthase inhibitor L-NAME or the cyclooxygenase inhibitor diclofenac did not significantly change superoxide production. Thus, these vascular sources of superoxide were not responsible for the increased superoxide concentration. In contrast, treatment with the NADPH oxidase inhibitor apocynin significantly decreased superoxide generation and improved vascular function. On the other hand, intrauterine undernutrition did not alter the gene expression for p22(phox) and gp91(phox). The fact that the local ANG II concentration was increased and the attenuation of oxidative stress by blocking AT(1) receptor with losartan, led us to suggest that ANG II induces O(2)(-) generation in intrauterine undernourished rats. CONCLUSION: Our study shows that NADPH oxidase inhibition attenuated superoxide anion generation and ameliorated vascular function in rats submitted to intrauterine undernutrition. Although it is not clear which mechanisms are responsible for the increase in NADPH oxidase activity, a role for ANG II-mediated superoxide production via activation of NADPH oxidase is suggested.     

<Emphasis Type="Italic">Acinetobacter</Emphasis> Infections in Neonates

Purpose of Review

MDR-Gram-negative bacteria are a great concern in the neonatal population, with a worldwide rise in the reported incidence and with very limited therapeutic options. Acinetobacter baumannii is responsible for many infections in neonates and outbreaks in neonatal intensive care unit (NICU); also, outbreaks caused by other Acinetobacter species have been reported. The aim of this review is to document the epidemiology of Acinetobacter spp. infections in neonates and risk factors for acquisition of Acinetobacter spp. in the NICU using data from published studies.

Recent Findings

Acinetobacter spp. infections are increasing in neonates in NICU. Outbreak caused by multidrug resistant (MDR) or extensively drug resistant (XDR) A. baumannii but also outbreak caused by susceptible A. soli and A. septicus sp. nov., were reported in neonates. Acinetobacter spp. were responsible for bloodstream infections and respiratory tract infections in neonates. Risk factors for A. baumannii acquisition in neonates were low birthweight, length of NICU stay, umbilical catheterization, central-venous catheterization, assisted ventilation, and prior antibiotic use.

Summary

This review highlights the importance of surveillance of risk factors for healthcare-associated infections in NICU to control MDR and XDR A. baumannii infections in neonates.

     

Status of allele frequency and diversity of Plasmodium falciparum msp1, msp2 and glurp before implementation of an artemisinin-based combined therapy in Northwestern Colombia.

Introduction:

The status of msp1, msp2 and glurp allele frequency and the diversity of Plasmodium falciparum in Northwestern Colombia before the implementation of an artemisinin-combined therapy have been explored only by a few authors and in a relatively small number of samples from this highly endemic region.

Objective:

To evaluate the frequency of msp1, msp2, and glurp alleles and the diversity of P. falciparum in two Colombian regions before the use of an artemisinin-combined therapy.

Methods:

This study was part of a major anti-malarial efficacy trial designed as a random, clinically-controlled study for which 224 subjects were recruited. Region 2 of msp1 and msp2 (central region) were amplified by a nested PCR; glurp (region R2) was amplified by a semi-nested PCR.

Results:

For msp1, five genotypes were observed, representing the K1, MAD20, and RO33 allelic families. All samples corresponded to a MAD20 150 bp allele. For msp2 (IC family), two alleles were detected and for glurp, eight were observed. A total 33 haplotypes were detected.

Conclusions:

Analysis of glurpcan be used to successfully genotype parasite populations in the new studies in Colombia aimed at exploring Plasmodium spp population dynamics. In addition, analysis of msp1 and msp2 can also be of value for comparisons with past studies, but not when the objective is to study parasites obtained from the same patient in a reduced period of time; for instance, during treatment efficacy studies.     

Characterization of the release profile of doxycycline by PLGA microspheres adjunct to non-surgical periodontal therapy

The aim of this pilot study was to assess the release of locally delivered doxycycline by poly (l-lactide-co-glycolide) (PLGA) microspheres in the periodontal pocket of patients with chronic periodontitis, treated by non-surgical periodontal therapy. Nineteen sites of non-adjacent teeth of four different patients were evaluated. Five milligram of PLGA microspheres loaded with 16 doxycycline hyclate (DOX) was administered per periodontal site. To quantify DOX released into the periodontal pocket, gingival crevicular fluid (GCF) was collected from the sites on days 2, 5, 7, 10, 15, and 20 after DOX application, and high-performance liquid chromatography was performed. Data were statistically assessed by ANOVA/Tukey test. At days 2, 5, and 7, the DOX concentration was stably sustained (23.33 ± 1.38, 23.4 ± 1.82, and 22.75 ± 1.33 μg/mL, respectively), with no significant differences over these assessment times (p > 0.05). At days 10 and 15, a tendency was observed toward a decrease in DOX concentration (21.74 ± 0.91 and 20.53 ± 4.88 μg/mL, respectively), but a significant decrease in GCF drug concentration (19.69 ± 4.70 μg/mL) was observed only on day 20. The DOX delivery system developed demonstrated a successful sustained release after local administration, as an adjunct to non-surgical periodontal therapy.     

Neurological disease caused by Oropouche virus in northern Brazil: should it be included in the scope of clinical neurological diseases?

Journal of NeuroVirology - We describe two neurological cases of Oropouche virus infection in northern Brazil, where the virus is endemic but neglected as a pathogen. This study reiterates the...     

Flow cytometry data mining by cytoChain identifies determinants of exhaustion and stemness in TCR-engineered T cells

The phenotype of infused cells is a major determinant of Adoptive T-cell therapy (ACT) efficacy. Yet, the difficulty in deciphering multiparametric cytometry data limited the fine characterization of cellular products. To allow the analysis of dynamic and complex flow cytometry samples, we developed cytoChain, a novel dataset mining tool and a new analytical workflow. CytoChain was challenged to compare state-of-the-art and innovative culture conditions to generate stem-like memory cells (T_SCM) suitable for ACT. Noticeably, the combination of IL-7/15 and superoxides scavenging sustained the emergence of a previously unidentified nonexhausted Fit-T_SCM signature, overlooked by manual gating and endowed with superior expansion potential. CytoChain proficiently traced back this population in independent datasets, and in T-cell receptor engineered lymphocytes. CytoChain flexibility and function were then further validated on a published dataset from circulating T cells in COVID-19 patients. Collectively, our results support the use of cytoChain to identify novel, functionally critical immunophenotypes for ACT and patients immunomonitoring.