Development of a New Multispecies Protein A-Based ELISA for Serodiagnosis of Hepatitis E Infection with Validation in Domestic Swine.

Hepatitis E virus (HEV) infects roughly 20 million people worldwide, causing self-limiting acute hepatic disease that can evolve into a chronic course. HEV-3, HEV-4, and HEV-7 genotypes are zoonotic and transmitted to humans by consuming raw or undercooked meat. Here, we developed an indirect ELISA based on the recombinant HEV-3 capsid and performed a seroprevalence study on domestic swine in northeastern Brazil. Our in-house ELISA was initially validated using a subset of 79 sera characterized by concordant results for two distinct commercial ELISA kits. Our ELISA exhibited excellent sensitivity (94%) and specificity (100%), with an area under the curve of 0.99 Further testing, including 212 swine sera, revealed a seroprevalence of 57.5% (95% confidence interval, 50.6-64.3%). Our findings indicate that the novel ELISA test could accurately detect specific anti-HEV antibodies in domestic pigs and should be further validated in humans and other mammals.

Benzonidazole treatment has a beneficial effect on cells infected with the Colombian strain of Trypanosoma cruzi.

Benznidazole (Bz) is the recommended drug for the treatment of Chagas disease; however, its efficacy may vary according to the sensitivity of Trypanosoma cruzi strains to the drug and host immune background. The study evaluated the immune response of peripheral blood mononuclear cells (PBMC) that were infected in vitro with the Colombian strain (Col) and treated with Bz. The co-cultures were incubated for 24 h, 5 and 10 days, where cytokine dosage was performed in the supernatant and evaluation of the cells for CD28+ and CTLA-4+ molecules in CD4+ and CD8+ lymphocytes, and CD80+ , CD86+ and HLA-DR+ in CD14+ cells. The results showed that Col induced a strong inflammatory response, with an increase in IFN-γ and TNF early in the infection (24 h), however, from 5 days of infection on, TNF production declined, and IL-10 production increased, which may be associated with a control mechanism of the exacerbated inflammatory response. The Bz treatment did not significantly alter the frequencies of the phenotypes evaluated both T cell subsets and CD14+ cells. Therefore, this study reinforces the need for typing the patient's strain to guide therapy and promote individualized treatment protocols due to the heterogeneous genetic background among T. cruzi strains.

Hierarchical evaluation of histology and p16-labeling can improve the risk assessment on cervical intraepithelial neoplasia progression.

OBJECTIVE: High-grade cervical lesions (HSIL) are associated with the presence of high-risk HPV types, tissue expression of p16, and increased chance of malignant progression, requiring surgical intervention. To improve risk evaluation, we assessed the discriminatory power of the histological findings associated with p16 immunohistochemistry (IHC) staining to classify the low-grade cervical lesion (LSIL) and HSIL. METHODS: We collected cervical biopsies from colposcopy-visible lesions and non-affected tissue (adjacent to the lesions) of 62 Brazilian women and labeled them with anti-p16 antibodies. In addition to the observational pattern and labeling to define the latent classes (affected vs. non-affected), a computational tool was used for semi-quantitative analysis of p16 expression. The intensity of staining of the nucleus or cytoplasm was captured using the Gimp 2.10 software. ROC curves were used to determine cutoff values for p16 expression in patients classified as LSIL and HSIL by latent class statistics for each labeling stratum. RESULTS: p16 nuclear labeling showed the best sensitivity and specificity to discriminate LSIL with low p16 expression (62%) and HSIL with high p16 expression (37%). Many patients whose lesions had intermediate levels of p16 nuclear staining were subsequently stratified according to the expression of p16 in the cytoplasm, indicating that five of 21 LSIL were at risk of progression, and 13 of 41 HSIL at risk of regression. CONCLUSIONS: We suggest a hierarchical analysis, with histology at the first level, followed by a labeling analysis in the nucleus and then in the cytoplasm to increase the accuracy of the HPV cervical lesion stratification.

Tick infestation on birds in an urban Atlantic Forest fragment in north-eastern Brazil.

Birds are important hosts for various tick species, playing a significant role in their biological life cycle and dispersion. In this study, we investigated tick infestations on birds trapped in an urban remnant of Atlantic Forest in Pernambuco state, Brazil. From February 2015 to March 2017, 541 birds belonging to 52 species were trapped with mist nets and examined for ectoparasites. Birds trapped in the late successional forest were significantly more infested than birds trapped in the early successional forest. In the same way, ectoparasite infestation varied significantly according to bird weight and collection plot. Overall, 198 birds (36.6%) belonging to 27 species were parasitized by ectoparasites (i.e., ticks, lice and/or mites). Ectoparasites were effectively collected from 111 birds, of which 99 belonging to 20 species were infested by ticks (n = 261), namely, Amblyomma longirostre (13 nymphs), Amblyomma nodosum (21 nymphs), Amblyomma varium (one nymph), and Amblyomma spp. (five nymphs and 221 larvae). Most of the ticks (> 90%) were collected from Passeriformes. This study provides the second record of A. varium in Pernambuco state and confirms that birds, especially Passeriformes, are important hosts for larvae and nymphs of Amblyomma spp. in the Atlantic Forest biome of Pernambuco.

Metallic elements in aquatic herpetofauna (Crocodylia; Testudines) from a lentic Atlantic rainforest environment in northeastern Brazil.

In the present study, Fe, Cu, Cr, Cd, Pb, Ni, and Al concentrations in Caiman latirostris and Testudines blood from the Tapacurá reservoir, Pernambuco, Brazil, were investigated. Blood was acid digested with HNO3, and metals were determined by ICP-OES and FAAS. Lead showed concentrations below the established limit of detection. Eighty animals were evaluated, forty from each group. The levels of all elements were statistically significant when compared between the two studied taxa (p < 0.05). In caimans, significant differences between young and adults were observed for chromium (p = 0.0539) and aluminum (p = 0.0515). Testudines showed no statistically significant differences for the variable age structure. Gender did not influence metal concentrations detected in the present study for either group. Differences between species of testudines were significant for Fe between Mesoclemmys tuberculata vs Phrynops geoffroanus (p = 0.0932) and Kinosternon scorpioides vs Phrynops geoffroanus (p = 0.063). The inter-elementary correlations showed statistically significant differences between the elements Cr vs Al (R2 = 0.52), Cr vs Cd (0.43), Cd vs Cu (R2 = 0.41), Ni vs Cu (R2 = 0.31), Ni vs Cr (R2 = 0.30), Al vs Cd (R2 = 0.27), and Cd vs Fe (R2 = 0.26). It is concluded that blood is an excellent predictor of metals in crocodilians and testudines in the Tapacurá reservoir, with statistically significant differences when correlated to concentrations such as size and species studied. In addition, it evidenced data that prove the exposure of these animals to metals, with strong inter-elementary correlations and opening doors for future studies that seek to understand possible biological effects caused in the studied taxa.

Body Mass Index Profile of Adult Patients with Inflammatory Bowel Disease in a Multicenter Study in Northeastern Brazil.

Purpose: Inflammatory bowel disease (IBD) is a disease of increasing prevalence in developing countries. Obesity has emerged as a potential risk for IBD; however, the data in the literature are conflicting, and relevant studies in Brazil are limited. Here, we report body mass index profile (BMI) of patients with IBD treated at reference centers in three states of northeastern Brazil. Patients and Methods: Observational descriptive study conducted from January 2021 through December 2021 in patient with IBD. Results: Of 470 patients with IBD, 194 (41%) were classified as normal weight, 42 (9%) as underweight, 155 (33%) as overweight, and 79 (17%) as obese; CD patients were significantly more likely to be underweight than UC patients (p=0.031)Overweight patients were older (median age: 47 years) than normal-weight and underweight patients at diagnosis (38.5 and 35.5 years, respectively [p<0.0001]). IBD onset and diagnosis among overweight and obese individuals were associated with older age. More extensive disease behavior patterns predominated in UC, while forms associated with complications were prevalent in CD, irrespective of nutritional status. There was a higher frequency of compatible symptoms with axial joint inflammation among obese patients (p=0.005) and a lower frequency of compatible symptoms with peripheral joint inflammation in underweight patients (p=0.044) than in patients of normal weight. No significant difference in the frequency of different drug or surgical treatments was observed among the groups. Conclusion: Despite the predominance of overweight and obesity in patients with IBD, no differences in the patterns of disease were seen between the overweight and normal-weight groups; however, obesity was associated with IBD onset in older adults and a higher frequency compatible symptom with axial joint inflammation. These data reinforce the importance of monitoring the nutritional status of IBD patients and the need for a multidisciplinary approach, as recommended in the current guidelines.

Longitudinal evolution of electroencephalogram (EEG): Findings over five years of follow-up in children with Zika-related microcephaly from the Microcephaly Epidemic Research Group Pediatric Cohort (2015-2020).

OBJECTIVE: To assess the longitudinal evolution of EEG findings in children with Zika related-microcephaly (ZRM) and to evaluate the associations of these patterns with the children's clinical and neuroimaging characteristics. METHODS: As part of the follow-up of the Microcephaly Epidemic Research Group Pediatric Cohort (MERG-PC) in Recife, Brazil, we performed serial EEG recordings in a subgroup of children with ZRM to evaluate changes in background rhythms and epileptiform activity (EA). Latent class analysis was used to identify patterns in the evolution of EA over time; clinical and neuroimaging findings were compared across the identified groups. RESULTS: Out of the 72 children with ZRM who were evaluated during 190 EEGs/videoEEGs, all participants presented with abnormal background activity, 37.5% presented with an alpha-theta rhythmic activity, and 25% presented with sleep spindles, which were less commonly observed in children with epilepsy. EA changed over time in 79.2% of children, and three distinct trajectories were identified: (i) multifocal EA over time, (ii) no discharges/focal EA evolving to focal/multifocal EA, and (iii) focal/multifocal EA evolving to epileptic encephalopathy patterns (e.g., hypsarrhythmia or continuous EA in sleep). The multifocal EA over time trajectory was associated with periventricular and thalamus/basal ganglia calcifications, brainstem and corpus callosum atrophy and had less focal epilepsy, whereas the children in the trajectory which evolved to epileptic encephalopathy patterns had more frequently focal epilepsy. SIGNIFICANCE: These findings suggest that, in most children with ZRM, trajectories of changes in EA can be identified and associated with neuroimaging and clinical features.

Performance of IS6110-LAMP assay for detection of Mycobacterium tuberculosis complex in blood and urine samples from patients with extrapulmonary tuberculosis.

BACKGROUND: The diagnosis of extrapulmonary tuberculosis (EPTB) shows numerous difficulties because of non-specific symptomatology and low sensitivity of conventional methods. Loop-mediated isothermal amplification (LAMP) is a fast and low-cost technique, which can amplify under isothermal conditions an amount of target DNA copies into approximately a billion copies. OBJECTIVE: The present study aimed to evaluate a IS6110-LAMP system for Mycobacterium tuberculosis detection in blood and urine samples from patients with EPTB. METHODS: The collected samples (n = 122) were stratified in two groups: Group EPTB - patient samples with confirmed EPTB (n = 61); Group non-TB - patient samples without TB (n = 61). The urine samples underwent decontamination, and the components of blood samples were separated (plasma and PBMC). DNA extractions were performed in all biological samples followed by IS6110-LAMP assay technique. The detection limit was evaluated through dilution curves (1:10) using Mtb reference strain (H37Rv) genomic DNA. FINDINGS: The detection limit of IS6110-LAMP was 10 fg/µL (∼10-20 bacilli/µL). The IS6110-LAMP technique sensitivity and specificity were 95.65 % and 79.25 %, respectively, with a general kappa agreement index of 0.762. MAIN CONCLUSIONS: Based on these results, IS6110-LAMP test showed considerable diagnostic parameters, being able to aid in the speed and accuracy of the final EPTB diagnosis.

A Multicentre Study of the Clinical and Epidemiological Profile of Inflammatory Bowel Disease in Northeast Brazil.

Purpose: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBDs) with multifactorial causes. They are becoming more prevalent in developing countries such as Brazil; however, relevant studies in poorer regions of the country are limited. Here, we report the clinical-epidemiological profile of patients with IBD treated at reference centers in three states of Northeast Brazil. Patients and Methods: This was a prospective cohort study involving patients at referral outpatient clinics for IBD from January 2020 through December 2021. Results: Of 571 patients with IBD, 355 (62%) had UC, and 216 (38%) had CD. The patients were predominantly women (355, 62%) for both UC and CD. Extensive colitis was the pattern present in 39% of the UC cases. For CD, ileocolonic disease was the predominant manifestation (38%), with 67% of cases showing penetrating and/or stenosing behavior. The majority of patients were diagnosed between the ages of 17 and 40, corresponding to 60.2% in CD and 52.7% in UC. The median time between symptom onset and diagnosis was 12 months for CD and 8 months for UC (p=0.042). Joint involvement was the most frequent extraintestinal manifestation, with arthralgia and arthritis present in 41.9% and 18.6% of the patients, respectively. Biological therapy was prescribed to 73% of CD patients and 26% of UC patients. A progressive increase in new cases was observed in every 5-year interval over the last five decades, with 58.6% being diagnosed in the last 10 years. Conclusion: More extensive disease behavior patterns predominated in UC, while forms associated with complications were prevalent in CD. A prolonged time to diagnosis may have contributed to these findings. A progressive increase in IBD incidence was observed and may be related to greater urbanization and better access to specialized outpatient clinics, resulting in improvements in diagnosis.

Associated factors for treatment delay in pulmonary tuberculosis in HIV-infected individuals: a nested case-control study.

BACKGROUND: The delay in initiating treatment for tuberculosis (TB) in HIV-infected individuals may lead to the development of a more severe form of the disease, with higher rates of morbidity, mortality and transmissibility. The aim of the present study was to estimate the time interval between the onset of symptoms and initiating treatment for TB in HIV-infected individuals, and to identify the factors associated to this delay. METHODS: A nested case-control study was undertaken within a cohort of HIV-infected individuals, attended at two HIV referral centers, in the state of Pernambuco, Brazil. Delay in initiating treatment for TB was defined as the period of time, in days, which was greater than the median value between the onset of cough and initiating treatment for TB. The study analyzed biological, clinical, socioeconomic, and lifestyle factors as well as those related to HIV and TB infection, potentially associated to delay. The odds ratios were estimated with the respective confidence intervals and p-values. RESULTS: From a cohort of 2365 HIV-infected adults, 274 presented pulmonary TB and of these, 242 participated in the study. Patients were already attending 2 health services at the time they developed a cough (period range: 1 - 552 days), with a median value of 41 days. Factors associated to delay were: systemic symptoms asthenia, chest pain, use of illicit drugs and sputum smear-negative. CONCLUSION: The present study indirectly showed the difficulty of diagnosing TB in HIV-infected individuals and indicated the need for a better assessment of asthenia and chest pain as factors that may be present in co-infected patients. It is also necessary to discuss the role played by negative sputum smear results in diagnosing TB/HIV co-infection as well as the need to assess the best approach for drug users with TB/HIV.

Neutralizing antibodies against SARS-CoV-2 in Brazilian pregnant women vaccinated with one or two doses of BNT162b2 mRNA vaccine (Pfizer/WyethTM).

Pregnant women have an increased risk of developing severe coronavirus disease. In Brazil, the number of hospitalizations and adverse outcomes, including death caused by COVID-19, in women during the pregnancy-puerperal cycle was high in the first pandemic year. Doubts regarding vaccines' efficacy and safety for the mother and fetus delayed vaccination. This study evaluated the generation of IgG titers and neutralizing antibodies to the BNT162b2 mRNA vaccine in 209 healthy pregnant women. For this, were used the QuantiVac ELISA (IgG) and SARS-CoV-2 NeutraLISA kits (EUROIMMUN, Lübeck, SH) following the manufacturer's recommendations. One dose vaccine produced anti-SARS-CoV-2 IgG in 85% (81/95), and two produced in 95% (76/80) women. Among unvaccinated women, four of 34 (12%) showed protection. The first dose of the BNT162b2 vaccine protected 69% of the women with neutralizing antibodies (median of %IH = 97). In the second dose, protection occurred in 94% of the pregnant women (median of IH% = 97). This study showed no differences in IgG antibody titers between one- and two-dose of the BNT162b2 mRNA vaccine groups, boosting with the second dose increased the number of women who produced specific IgG and neutralizing antibodies, raising by 114-folds the chance of producing the SARS-CoV-2 neutralizing antibodies compared to the unvaccinated pregnant woman, which may contribute to reduce the chance of severe COVID-19.

Cytokines and Soluble HLA-G Levels in the Acute and Recovery Phases of Arbovirus-Infected Brazilian Patients Exhibiting Neurological Complications.

Severe neurological complications following arbovirus infections have been a major concern in seasonal outbreaks, as reported in the Northeast region of Brazil, where the same mosquito transmitted Zika (ZIKV), Dengue (DENV), and Chikungunya (CHIKV) viruses. In this study, we evaluated the levels of 36 soluble markers, including cytokines, chemokines, growth factors, and soluble HLA-G (Luminex and ELISA) in: i) serum and cerebrospinal fluid (CSF), during the acute phase and two years after the infection (recovery phase, only serum), ii) the relationship among all soluble molecules in serum and CSF, and iii) serum of infected patients without neurological complications, during the acute infection. Ten markers (sHLA-G, IL-10, IL-22, IL-8, MIP-1α, MIP-1ß, MCP-1, HGF, VEGF, and IL-1RA) exhibited differential levels between the acute and recovery phases, with pronounced increases in MIP-1α (P<0.0001), MCP-1 (P<0.0001), HGF (P= 0.0001), and VEGF (P<0.0001) in the acute phase. Fourteen molecules (IL-1ß, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-13, IL-15, IL-17A, IFN-α, TNF, and G-CSF) exhibited distinct levels between arbovirus patients presenting or not neurological complications. IL-8, EGF, IL-6, and MCP-1 levels were increased in CSF, while RANTES and Eotaxin levels were higher in serum. Soluble serum (IL-22, RANTES, Eotaxin) and CSF (IL-8, EGF, IL-3) mediators may discriminate putative risks for neurological complications following arbovirus infections. Neurological complications were associated with the presence of a predominant inflammatory profile, whereas in non-complicated patients an anti-inflammatory profile may predominate. Mediators associated with neuroregeneration (EGF and IL-3) may be induced in response to neurological damage. Broad spectrum immune checkpoint molecules (sHLA-G) interact with cytokines, chemokines, and growth factors. The identification of soluble markers may be useful to monitor neurological complications and may aid in the development of novel therapies against neuroinflammation.

The 1G/1G+1G/2G Genotypes of MMP1 rs1799750 Are Associated with Higher Levels of MMP-1 and Are Both Associated with Lipodystrophy in People Living with HIV on Antiretroviral Therapy.

In HIV-infected patients, antiretroviral therapy (ART) is associated to adipose tissue redistribution known as lipodystrophy (LD). This study aimed at verifying the association between the polymorphism of the MMP1 gene (rs1799750) (1G/2G) and the serum levels of matrix metalloproteinase 1 (MMP-1) with LD and its subtypes in people living with HIV on ART. This is a cross-secional study. LD was self-reported. The determination of the MMP1 rs1799750 gene polymorphism was performed by real-time PCR, and the serum concentrations of MMP-1 were quantified by the enzyme-linked immunosorbent assay (ELISA) method. Of 404 participants, 204 (51%) were diagnosed with LD, of whom 89 (43%) had mixed lipodystrophy (ML), 72 (35%) had lipohypertrophy (LH), and 43 (22%) had lipoatrophy (LA). There was an association between the genotypes 1G/1G+1G/2G and higher serum levels of MMP-1 (p = .025). There was no association of MMP1 (1G/2G) with LD. Other factors associated with LD were current CD4 ≤ 350 [odds ratio (OR) = 4.85, confidence interval (CI) = 1.78-47.99, p = .0033] and serum MMP-1 levels >6.81 (OR = 2.67, CI = 1.21-6.08, p = .0165). Factors associated with ML: current CD4 ≤ 350 (OR = 5.59, CI = 1.69-20.39, p = .006); with LH: number of antiretroviral regimens used: 2 (OR = 2.06, CI = 1.01-4.20, p = .0460) and 3+ (OR = 2.09, CI = 1.00-4.35, p = .0477), and current CD4 ≤ 350 (OR = 2.08, CI = 1.00-4.24, p = .0461); and with LA: current viral load >40 (OR = 2.52, CI = 1.03-5.91, p = .0372) and current use of zidovudine (OR = 2.97, CI = 1.32-6.54, p = .0074). Higher levels of MMP-1 were associated with genotypes 1G/2G+1G/1G and with LD. Other individual risk factors were independently associated with LD, and its subtypes, suggesting that the pathogenesis itself is differently manifested for each type of LD.

Correlation of biological serum markers with the degree of hepatic fibrosis and necroinflammatory activity in hepatitis C and schistosomiasis patients.

Liver biopsy is the gold-standard method to stage fibrosis; however, it is an invasive procedure and is potentially dangerous. The main objective of this study was to evaluate biological markers, such as cytokines IL-13, IFN-gamma, TNF-alpha and TGF-beta, platelets, bilirubins (Bil), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total proteins, gamma-glutamil transferase (gamma-GT) and alkaline phosphatase (AP), that could be used to predict the severity of hepatic fibrosis in schistosomiasis and hepatitis C (HC) as isolated diseases or co-infections. The following patient groups were selected: HC (n = 39), HC/hepatosplenic schistosomiasis (HSS) (n = 19), HSS (n = 22) and a control group (n = 13). ANOVA and ROC curves were used for statistical analysis. P < 0.05 was considered significant. With HC patients we showed that TNF-alpha (p = 0.020) and AP (p = 0.005) could differentiate mild and severe fibrosis. With regard to necroinflammatory activity, AST (p = 0.002), gamma-GT (p = 0.034) and AP (p = 0.001) were the best markers to differentiate mild and severe activity. In HC + HSS patients, total Bil (p = 0.008) was capable of differentiating between mild and severe fibrosis. In conclusion, our study was able to suggest biological markers that are non-invasive candidates to evaluate fibrosis and necroinflammatory activity in HC and HC + HSS.

Social conditions and immune response in human immunodeficiency virus-seropositive pregnant women: a cross-sectional study in Brazil.

INTRODUCTION: The functioning of the immune system during pregnancy is altered in both human immunodeficiency virus (HIV)-infected and uninfected women. Unfavorable socioeconomic conditions have been indicative of higher morbidity and mortality and worsening of the immune system. The aim of this study was to correlate social status with levels of interleukin (IL)-10 (non-inflammatory) and interferon-gamma (IFN-γ; inflammatory) cytokines. METHODS: A cross-sectional study was conducted with three groups of women: 33 pregnant HIV-infected (G1); 40 non-pregnant, HIV-infected (G2); and 35 pregnant, HIV-uninfected. To measure the social status, a compound indicator called the social status index (SSI), was established using sociodemographic variables (i.e., education level, housing conditions, per capita income, and habitation and sanitary conditions). RESULTS: The HIV-infected women had a higher proportion of unfavorable SSI (73% and 75% of G1 and G2, respectively). There were significantly lower IL-10 levels in the G1 group with both unfavorable and favorable SSI than in the other groups. No significant difference in IFN-γ levels was observed among groups. However, the G1 group had higher IFN-γ values among both favorable and unfavorable SSI groups. CONCLUSIONS: Higher rates of unfavorable conditions, including lower education levels, IL-10 levels, and a trend for higher IFN-γ levels, were identified among HIV-infected women, pregnant and non-pregnant. These factors may interfere in health care and lead to poor outcomes during pregnancy. Therefore, we suggest that health policies could be created to specifically address these factors in this population.

HLA-G is expressed in intestinal samples of ulcerative colitis and Crohn's disease patients and HLA-G5 expression is differentially correlated with TNF and IL-10 cytokine expression.

HLA-G is an immunomodulatory molecule that can be produced by epithelial cells. Considering that TNF and IL-10 participate in bowel inflammatory disorders and that both cytokines modulate HLA-G, we evaluated HLA-G, TNF and IL-10 mRNA expression by qPCR and HLA-G protein levels by immunohistochemistry in two intestinal samples exhibiting different degree of inflammation within a patient suffering from Crohn's disease (CD) or ulcerative colitis (UC). Tissue HLA-G5 (P < 0.0001), TNF (P = 0.0004) and IL-10 (P = 0.0169) mRNA expression levels were higher in intestinal areas exhibiting intense inflammation compared to areas of low inflammation, and HLA-G protein levels were not associated with degree of mucosal inflammation. In CD, the expression of TNF was correlated with IL-10 in low inflamed areas, exhibiting a TNF:IL-10 ratio = 3, but in inflamed areas the ratio increased to 9-folds. In UC, the expression of TNF was correlated to IL-10, irrespective of the inflammation grade, with little variation of the TNF:IL-10 ratio in the various inflamed areas. TNF and IL-10 expression was correlated with HLA-G5 expression in mild inflamed areas. Both CD and UC samples exhibited gene and protein expression of HLA-G; and the HLA-G5 expression is differentially correlated with TNF and IL-10 levels depending on the type of the underlying inflammatory bowel disorder.

Variation sites at the HLA-G 3' untranslated region confer differential susceptibility to HIV/HPV co-infection and aneuploidy in cervical cell.

Post-transcriptional regulatory elements associated with transcript degradation or transcript instability have been described at the 3' untranslated region (3'UTR) of the HLA-G gene. Considering that HPV infection and aneuploidy, which causes gene instability, are associated with cervical cell malignancy, as well as the fact that HIV infection and HLA-G may modulate the immune response, the present study aimed to compare the frequencies of HLA-G 3'UTR polymorphic sites (14-base pair insertion/deletion, +3142C/G, and +3187A/G) between 226 HIV+ women co-infected (n = 82) or not with HPV (n = 144) and 138 healthy women. We also evaluated the relationship between those HLA-G 3'UTR variants and aneuploidy in cervical cells. HPV types and HLA-G polymorphisms were determined by PCR and sequencing of cervical samples DNA. Aneuploidy in cervical cell was measured by flow cytometry. The HLA-G 3'UTR 14-bp ins/del was not associated with either HIV nor HIV/HPV co-infection. The +3142G allele (p = 0.049) and +3142GG genotype (p = 0.047) were overrepresented in all HIV-infected women. On the other hand, the +3187G allele (p = 0.028) and the +3187GG genotype (p = 0.026) predominated among healthy women. The +3142G (p = 0.023) and +3187A (p = 0.003) alleles were associated with predisposition to HIV infection, irrespective of the presence or not of HIV/HPV co-infection. The diplotype formed by the combination of the +3142CX (CC or CG) and +3187AA genotype conferred the highest risk for aneuploidy in cervical cell induced by HPV. The HLA-G 3'UTR +3142 and +3187 variants conferred distinct susceptibility to HIV infection and aneuploidy.

A comercialização de agrotóxicos e o modelo químico-dependente da agricultura do Brasil / The commercialization of pesticides and the chemical-dependent model of agriculture in Brazil

RESUMO Com o objetivo de analisar a comercialização de agrotóxicos no Brasil, suas regiões e estados, desenvolveu-se um estudo ecológico de série temporal no período de 2000 a 2014. Foram utilizados os dados sobre vendas de agrotóxicos do Instituto Brasileiro do Meio Ambiente e dos Recursos Naturais Renováveis e do Sindicato Nacional da Indústria de Produtos para Defesa Vegetal. A comercialização de agrotóxicos foi calculada como o quociente da quantidade de ingredientes ativos, em quilogramas, e a área plantada das principais lavouras, em hectares, anualmente, nos estados e regiões. Os programas Excel® e R foram utilizados para processamento e análise dos dados. Para análise de tendência, utilizou-se a regressão linear com nível de significância de 5%. Observou-se tendência à elevação da comercialização em todas as regiões do País no período (p<0,001), com o maior registro no Sudeste (4,88 kg/ha/ano); e o maior incremento nas regiões Norte e Nordeste. As maiores médias de vendas, em kg/ha/ano, ocorreram em São Paulo (8,43), Goiás (5,34) e Mato Grosso (4,92). O maior incremento de vendas por estado no período ocorreu no Acre (99,52%), Piauí (94,19%) e Distrito Federal (91,55%). Tornam-se imperativas medidas de regulação, fiscalização e normatização contra o agravamento da situação de saúde da população e contaminação do ambiente.

ABSTRACT Aiming to analyzing the commercialization of pesticides in Brazil, its regions and states, an ecological time series study was developed from 2000 to 2014, based on data on sales of pesticides from the Brazilian Institute of the Environment and Renewable Natural Resources and the National Union of Plant Protection Products Industry. The commercialization was calculated as the quotient of the quantity of active ingredients, in kilograms, and the planted area of the main crops, in hectares, annually in the states and regions. The Excel® and R programs were used for data analysis. For trend analysis, linear regression was used with a 5% significance level. There was a trend towards an increase in sales in all regions of the country in the period (p<0.001), with the highest record in the Southeast (4.88 kg/ha/year), and the largest increase in the North and Northeast regions. The highest average sales, in kg/ha/year, occurred in São Paulo (8.43), Goiás (5.34), and Mato Grosso (4.92). The biggest increase in sales by state occurred in Acre (99.52%), Piauí (94.19%), and Distrito Federal (91.55%). Regulatory, inspection, and standardization measures against the worsening of the population's health situation and contamination of the environment are imperative.

New index for the diagnosis of liver fibrosis in Schistosomiasis mansoni.

BACKGROUND: - Periportal fibrosis is the major pathological consequence of the Schistosoma mansoni infection. OBJECTIVE: - To evaluate the accuracy of serum markers and to construct an index to assess fibrosis. METHODS: - Patients (n=116) with schistosomiasis were evaluated by ultrasound scan and measurements of serum levels of aminotransferases, γ-glutamyl transferase, alkaline phosphatase, hyaluronic acid, cytokines and platelets. Ultrasound images were used to evaluate the fibrosis using Niamey's classification and identified 19 patients without periportal fibrosis (patterns A and B), 48 with mild to moderate fibrosis (C and D) and 49 with advanced fibrosis (E and F). RESULTS: - Using multivariate analysis, a model was created, which involved alkaline phosphatase and platelets and could separate patients with different patterns of fibrosis. This index showed a better performance in separating patients without fibrosis from with advanced periportal fibrosis. The biological index showed an area under the ROC curve of 1.000. Using values below the lowest or above the highest cut-off point, the presence or absence of advanced fibrosis could be predicted in all patients. CONCLUSION: - The index constructed can be used to separate patients with different patterns of periportal fibrosis, specially to predict advanced fibrosis in schistosomiasis patients.

Evaluation of serum levels of IL-9 and IL-17 in human Schistosoma mansoni infection and their relationship with periportal fibrosis.

Serum levels of IL-9 and IL-17 cytokines were evaluated in patients in the acute, chronic phases and clinical forms of human schistosomiasis and in different classifications of periportal fibrosis. No significant differences between the groups of the disease with serum levels of cytokine were found. However, this study discusses the results of some cytokines that have not fully defined roles in the pathology of human schistosomiasis. Furthermore, an examination was made of subjects in the acute phase. This is an important group that is difficult to identify in areas where the disease is endemic. More studies are being undertaken to study the role of IL-9 and IL-17 in human Schistosoma mansoni infection and their relationship with the immunopathogenesis of disease.