Virtual Learning Environment of the Brazilian Health System (AVASUS): Efficiency of Results, Impacts, and Contributions.

The Virtual Learning Environment of the Brazilian Health System (AVASUS) is a free and open distance education platform of the Ministry of Health (MS). AVASUS is a scalable virtual learning environment that has surpassed 800,000 users, 2 million enrollments, and 310 courses in its catalog. The objective of this paper was to assess the impacts of the educational offerings on health services and AVASUS course participants' professional practice. This study analyzed data from AVASUS, the Brazilian National Registry of Health Care Facilities (CNES), the Brazilian Occupational Classification (CBO), and a questionnaire applied to 720-course participants from five regions of Brazil. After acquiring and extracting data, computational methods were used for the evaluation process. Only the responses of 462 participants were considered for data analysis, as they had a formal link to CNES. The results showed that respondents recommended 76.2% of AVASUS courses to peers. Accordingly, the quality of educational offerings motivated 81.3% of such recommendations. In addition, 75.6% of course participants who answered the questionnaire also indicated that AVASUS course contents contribute to enhancing existing health services in the health facilities where they work. Finally, 24.6% of all responses mentioned that courses available in AVASUS were essential in offering new health services in such facilities.

The Text Mining Technique Applied to the Analysis of Health Interventions to Combat Congenital Syphilis in Brazil: The Case of the "Syphilis No!" Project.

Congenital syphilis (CS) remains a threat to public health worldwide, especially in developing countries. To mitigate the impacts of the CS epidemic, the Brazilian government has developed a national intervention project called "Syphilis No." Thus, among its range of actions is the production of thousands of writings featuring the experiences of research and intervention supporters (RIS) of the project, called field researchers. In addition, this large volume of base data was subjected to analysis through data mining, which may contribute to better strategies for combating syphilis. Natural language processing is a form of knowledge extraction. First, the database extracted from the "LUES Platform" with 4,874 documents between 2018 and 2020 was employed. This was followed by text preprocessing, selecting texts referring to the field researchers' reports for analysis. Finally, for analyzing the documents, N-grams extraction (N = 2,3,4) was performed. The combination of the TF-IDF metric with the BoW algorithm was applied to assess terms' importance and frequency and text clustering. In total, 1019 field activity reports were mined. Word extraction from the text mining method set out the following guiding axioms from the bigrams: "confronting syphilis in primary health care;" "investigation committee for congenital syphilis in the territory;" "municipal plan for monitoring and investigating syphilis cases through health surveillance;" "women's healthcare networks for syphilis in pregnant;" "diagnosis and treatment with a focus on rapid testing." Text mining may serve public health research subjects when used in parallel with the conventional content analysis method. The computational method extracted intervention activities from field researchers, also providing inferences on how the strategies of the "Syphilis No" Project influenced the decrease in congenital syphilis cases in the territory.

Studies Into ß-Glucan Recognition in Fish Suggests a Key Role for the C-Type Lectin Pathway.

Immune-modulatory effects of ß-glucans are generally considered beneficial to fish health. Despite the frequent application of ß-glucans in aquaculture practice, the exact receptors and downstream signalling remains to be described for fish. In mammals, Dectin-1 is a member of the C-type lectin receptor (CLR) family and the best-described receptor for ß-glucans. In fish genomes, no clear homologue of Dectin-1 could be identified so far. Yet, in previous studies we could activate carp macrophages with curdlan, considered a Dectin-1-specific ß-(1,3)-glucan ligand in mammals. It was therefore proposed that immune-modulatory effects of ß-glucan in carp macrophages could be triggered by a member of the CLR family activating the classical CLR signalling pathway, different from Dectin-1. In the current study, we used primary macrophages of common carp to examine immune modulation by ß-glucans using transcriptome analysis of RNA isolated 6 h after stimulation with two different ß-glucan preparations. Pathway analysis of differentially expressed genes (DEGs) showed that both ß-glucans regulate a comparable signalling pathway typical of CLR activation. Carp genome analysis identified 239 genes encoding for proteins with at least one C-type Lectin Domains (CTLD). Narrowing the search for candidate ß-glucan receptors, based on the presence of a conserved glucan-binding motif, identified 13 genes encoding a WxH sugar-binding motif in their CTLD. These genes, however, were not expressed in macrophages. Instead, among the ß-glucan-stimulated DEGs, a total of six CTLD-encoding genes were significantly regulated, all of which were down-regulated in carp macrophages. Several candidates had a protein architecture similar to Dectin-1, therefore potential conservation of synteny of the mammalian Dectin-1 region was investigated by mining the zebrafish genome. Partial conservation of synteny with a region on the zebrafish chromosome 16 highlighted two genes as candidate ß-glucan receptor. Altogether, the regulation of a gene expression profile typical of a signalling pathway associated with CLR activation and, the identification of several candidate ß-glucan receptors, suggest that immune-modulatory effects of ß-glucan in carp macrophages could be a result of signalling mediated by a member of the CLR family.

ß-Glucan successfully stimulated the immune system in different jawed vertebrate species.

Several reports have shown the positive effects of ß-glucans on the immune. Howeverthese studies have a broad experimental design including ß-glucans compounds. Consequently, a study using the same ß-glucan molecule, administration route and experimental design is needed to compare the effects of ß-glucan across vertebrate species. For this end, during 28 days we fed four different vertebrate species: mice, dogs, piglets and chicks, with two ß-glucan molecules (BG01 and BG02). We measured the serum interleukin 2 as an indicator of innate immune response, the neutrophils and monocytes phagocytosis index as a cellular response and antibody formation as an adaptive response. The results clearly showed that the different ß-glucan molecules exhibited biologically differently behaviors, but both molecules stimulate the immune system in a similar pattern in these four species. This finding suggests that vertebrates shared similar mechanisms/patterns in recognizing the ß-glucans and confirms the benefits of ß-glucans across different vertebrate species.

BALB/c mice infected with DENV-2 strain 66985 by the intravenous route display injury in the central nervous system.

Dengue is a mild flu-like arboviral illness caused by dengue virus (DENV) that occurs in tropical and subtropical countries. An increasing number of reports have been indicating that dengue is also associated to neurological manifestations, however, little is known regarding the neuropathogenesis of the disease. Here, using BALB/c mice intravenously infected with DENV-2 strain 66985, we demonstrated that the virus is capable of invading and damaging the host's central nervous system (CNS). Brain and cerebellum of infected animals revealed histological alterations such as the presence of inflammatory infiltrates, thickening of pia matter and disorganization of white matter. Additionally, it was also seen that infection lead to altered morphology of neuroglial cells and apoptotic cell death. Such observations highlighted possible alterations that DENV may promote in the host's CNS during a natural infection, hence, helping us to better understand the neuropathological component of the disease.

Correction: Peripheral Organs of Dengue Fatal Cases Present Strong Pro-Inflammatory Response with Participation of IFN-Gamma-, TNF-Alpha- and RANTES-Producing Cells.

[This corrects the article DOI: 10.1371/journal.pone.0168973.].

Placental Histopathology and Clinical Presentation of Severe Congenital Zika Syndrome in a Human Immunodeficiency Virus-Exposed Uninfected Infant.

In the large Zika virus (ZIKV) epidemic that occurred in Brazil in 2015, the intrauterine fetal exposure to ZIKV was associated with a significant risk of developing microcephaly and neurological disorders in the infected infants. ZIKV-associated disease has since been reported in 24 countries in the Americas. At present, definitive evidence is lacking regarding the intrauterine co-exposure to ZIKV and other viral infections and whether the coinfection impacts the risk of acquiring either infection or disease severity. Here, we provide evidence of intrauterine exposure to both ZIKV and human immunodeficiency virus (HIV) infections, causing congenital Zika syndrome in an HIV-exposed uninfected infant. Clinical, imaging and laboratory examinations of the pregnant woman and the newborn were performed. Histopathology, ZIKV/HIV-specific immunoassays, and ultrastructural evaluation of the placenta were performed. The Zika-asymptomatic, HIV-positive pregnant woman underwent ultrasounds revealing fetal cerebral ventriculomegaly, microcephaly, and brain atrophy. Her baby girl was born small for gestational age and with the neurological sequelae of congenital Zika syndrome. The evaluation of the abnormally large term placenta revealed severe damage to the maternal decidua and chorionic villi, cells positive for ZIKV-specific antigens but not for HIV antigens, and intracellular membranous clusters of virus-like particles approximately 25 nm in diameter. The rapid progression and severity of the congenital Zika syndrome may be related to the uncontrolled HIV disease in the mother. The poor inflammatory response observed in the placenta may have reduced the inherent risk of mother-to-child transmission of HIV.

Dengue fatal cases present virus-specific HMGB1 response in peripheral organs.

Dengue is an important infectious disease that presents high incidence and yields a relevant number of fatal cases (about 20,000) every year worldwide. Despite its epidemiological relevance, there are many knowledge gaps concerning dengue pathogenesis, especially with regards to the circumstances that drive a mild clinical course to a severe disease. In this work, we investigated the participation of high mobility group box 1 (HMGB1), an important modulator of inflammation, in dengue fatal cases. Histopathological and ultrastructural analyses revealed that liver, lung and heart post-mortem samples were marked by tissue abnormalities, such as necrosis and apoptotic cell death. These observations go in line with an HMGB1-mediated response and raised concerns regarding the participation of this cytokine in promoting/perpetuating inflammation in severe dengue. Further experiments of immunohistochemistry (IHC) showed increased expression of cytoplasmic HMGB1 in dengue-extracted tissues when compared to non-dengue controls. Co-staining of DENV RNA and HMGB1 in the host cell cytoplasm, as found by in situ hybridization and IHC, confirmed the virus specific induction of the HMGB1-mediated response in these peripheral tissues. This report brings the first in-situ evidence of the participation of HMGB1 in severe dengue and highlights novel considerations in the development of dengue immunopathogenesis.

Staphylococcus aureus in Some Brazilian Dairy Industries: Changes of Contamination and Diversity.

Staphylococcus aureus, a major food-poisoning pathogen, is a common contaminant in dairy industries worldwide, including in Brazil. We determined the occurrence of S. aureus in five dairies in Brazil over 8 months. Of 421 samples, 31 (7.4%) were positive for S. aureus and prevalence varied from 0 to 63.3% between dairies. Sixty-six isolates from the 31 samples were typed by Multi-Locus Sequence Typing to determine if these isolates were persistent or continuously reintroduced. Seven known sequence types (STs), ST1, ST5, ST30, ST97, ST126, ST188 and ST398, and four new ST were identified, ST3531, ST3540, ST3562 and ST3534. Clonal complex (CC) 1 (including the four new ST), known as an epidemic clone, was the dominant CC. However, there were no indications of persistence of particular ST. The resistance toward 11 antibiotic compounds was assessed. Twelve profiles were generated with 75.8% of strains being sensitive to all antibiotic classes and no Methicillin-resistant S. aureus (MRSA) strains were found. The enterotoxin-encoding genes involved in food-poisoning, e.g., sea, sed, see, and seg were targeted by PCR. The two toxin-encoding genes, sed and see, were not detected. Only three strains (4.5%) harbored seg and two of these also harbored sea. Despite the isolates being Methicillin-sensitive S. aureus (MSSA), the presence of CC1 clones in the processing environment, including some harboring enterotoxin encoding genes, is of concern and hygiene must have high priority to reduce contamination.

New Composites LnBDC@AC and CB[6]@AC: From Design toward Selective Adsorption of Methylene Blue or Methyl Orange.

New porous composites LnBDC@AC (AC = Activated carbon, Ln = Eu and Gd and BDC = 1,4-benzenedicaboxylate) and CB[6]@AC (CB[6] = Cucurbit[6]uril) were obtained using hydrothermal route. The LnBDC and CB[B] are located inside the pore of the carbon materials as was observed in SEM-EDS, XRPD and FT-IR analysis. Porosimetry analysis showed values typically between AC and LnBDC material, with pore size and surface area, respectively, 29,56 Å and 353.98 m2g-1 for LnBDC@AC and 35,53 Å and 353.98 m2g-1 for CB[6]@AC. Both materials showed good absorptive capacity of metil orange (MO) and methylene blue (MB) with selectivity as a function of pH. For acid pH, both materials present selectivity by MB and alkaline pH for MO, with notable performance for CB[6]@AC. Additionally, europium luminescence was used as structural probe to investigate the coordination environment of Eu3+ ions in the EuBDC@AC composite after adsorption experiment.

Peripheral Organs of Dengue Fatal Cases Present Strong Pro-Inflammatory Response with Participation of IFN-Gamma-, TNF-Alpha- and RANTES-Producing Cells.

Dengue disease is an acute viral illness caused by dengue virus (DENV) that can progress to hemorrhagic stages leading to about 20000 deaths every year worldwide. Despite many clinical investigations regarding dengue, the immunopathogenic process by which infected patients evolve to the severe forms is not fully understood. Apart from differences in virulence and the antibody cross reactivity that can potentially augment virus replication, imbalanced cellular immunity is also seen as a major concern in the establishment of severe dengue. In this context, the investigation of cellular immunity and its products in dengue fatal cases may provide valuable data to help revealing dengue immunopathogenesis. Here, based in four dengue fatal cases infected by the serotype 3 in Brazil, different peripheral organs (livers, lungs and kidneys) were studied to evaluate the presence of cell infiltrates and the patterns of local cytokine response. The overall scenario of the studied cases revealed a considerable systemic involvement of infection with mononuclear cells targeted to all of the evaluated organs, as measured by immunohistochemistry (IHC). Quantification of cytokine-expressing cells in peripheral tissues was also performed to characterize the ongoing inflammatory process by the severe stage of the disease. Increased levels of IFN-γ- and TNF-α-expressing cells in liver, lung and kidney samples of post-mortem subjects evidenced a strong pro-inflammatory induction in these tissues. The presence of increased RANTES-producing cell numbers in all analyzed organs suggested a possible link between the clinical status and altered vascular permeability. Co-staining of DENV RNA and IFN-γ or TNF-α using in situ hibridization and IHC confirmed the virus-specific trigger of the pro-inflammatory response. Taken together, this work provided additional evidences that corroborated with the traditional theories regarding the "cytokine storm" and the occurrence of uneven cellular immunity in response to DENV as major reasons for progress to severe disease.

Evaluation of a special combination of glucan with organic selenium derivative in different murine tumor models.

ß-glucans are well-established immunomodulators with strong effects resulting in slowing or even inhibiting cancer growth. Recent studies have repeatedly suggested that the biological activities of ß-glucan can be potentiated by the addition of other bioactive agents. In the current study, we focused on the anticancer effects of a combination of yeast-derived ß-glucan and a selenium-linked pseudodisaccharide. Using three different models of murine cancer, we showed that this combination strongly suppressed the growth of all three types of cancers, most likely via the interaction with natural anticancer antibodies.

New lanthanide-CB[6] coordination compounds: relationships between the crystal structure and luminescent properties.

The reaction between cucurbit[6]uril (CB[6]) and lanthanide chlorides (Eu, Sm, Tb and Tm) in acidic aqueous media led to four new structures. The compounds obtained are isostructural with general formula [Ln2(H2O)12(H2O@CB[6])]Cl6(H2O)4 (Ln = Eu(3+) (1), Sm(3+) (2), Tb(3+) (3) and Tm(3+) (4)) and crystallize in the P21/c space group. For the complexes with Eu(3+), Sm(3+) and Tb(3+), the luminescent properties in the solid state and aqueous media were explored and all spectroscopic observations are in excellent agreement with the single crystal structure data. The excitation and emission spectra show the typical f-f transitions characteristic of the trivalent lanthanide ions. The transitions (7)FJ ← (5)D1 (J = 0,1,2) in the europium compound and (7)FJ ← (5)D4 (J = 0,1,2) in the terbium compound, not yet reported in lanthanide-CB[n] compounds, were also observed.

Photoinactivation of different human tumor cell lines and sheep red blood cells in vitro by liposome-bound Zn(II) Phthalocyanine: Effects of cholesterol.

The in vitro photoinactivation of human tumor cell lines and sheep red blood cells (SRBC) by Zinc (II) Phthalocyanine (ZnPc) was investigated using unilamellar liposome (LUV) as delivery system, in the presence and absence of cholesterol (CHOL) in the formulation. The presence of CHOL improves the stability of the system showing to be essential for the photodynamic action of ZnPc. LUVs prepared without CHOL did not present any antiproliferative effects neither induced significant photohaemolysis. The presence of ZnPc in the culture medium caused total cell growth inhibition (TGI) only at concentrations higher than 250 micromol dm(-3). For ZnPc in LUV/CHOL (mass ratio=3:1), the mean TGI values for almost all studied cells were around 80 micromol dm(-3), and 14 micromol dm(-3) for human ovarian carcinoma (NIH: OVCAR-3) cells. The cytoplasmic components of OVCAR-3 and SRBC when irradiated in presence of ZnPc in LUV/CHOL were completely destroyed, culminating in cell swelling, lysis and death by necrosis.

Colic caused by Panicum maximum toxicosis in equidae in northern Brazil.

In the Amazon region of northern Brazil, Panicum maximum cultivars Mombaça, Tanzânia, and Massai cause severe colic and death in horses and mules. The disease occurs in the rainy season, when sprouting pastures are grazed by equidae. In the 8 separate disease outbreaks studied, a total of 52 out of 153 equidae were affected, including 19 that died (10 mules and 9 horses). Clinical signs were colic and abdominal dilatation, with a clinical manifestation period of 12 hr to 4 days. Serum activities of gamma-glutamyl transferase and aspartate aminotransferase were within reference intervals; however, serum urea nitrogen and creatinine concentrations were occasionally elevated. The primary gross and histologic lesions were observed in the digestive system. The stomach, small intestine, and large intestine had severe hemorrhages and occasional mucosal erosions and ulcerations. Ulceration and hemorrhage of the urinary bladder were rarely observed. Histologic examination revealed diffuse lymphoplasmacytic gastritis and enteritis with severe congestion, hemorrhage, and occasional epithelial necrosis and ulceration. Lymphocellular necrosis was occasionally observed within gut-associated lymphoid tissue. Tubular nephrosis occurred in some animals. Degeneration and occasional necrosis of bile duct epithelial cells and degeneration of hepatocytes were observed in the liver. Toxic pastures were negative for diosgenin- and yamogenin-based saponins, and oxalate concentrations were within reference intervals for the species. The toxin or toxins causing disease and the reason for the toxicity of the plant in the northern region are unknown.

[Biology of Agistemus brasiliensis Matioli, Ueckermann & Oliveira (Acari: Stigmaeidae) and its predation potential on Brevipalpus phoenicis (Geijskes) (Acari: Tenuipalpidae)]. / Biologia de Agistemus brasiliensis Matioli, Ueckermann & Oliveira (Acari: Stigmaeidae) e sua potencialidade de predação sobre Brevipalpus phoenicis (Geijskes) (Acari: Tenuipalpidae).

The present work aimed to study the biology of Agistemus brasiliensis Matioli, Ueckermann & Oliveira at the following temperatures, namely 15, 20, 25, 30 and 35 degrees C, fed with Brevipalpus phoenicis (Geijskes) and Typha pollen, in laboratory conditions. Life tables were calculated to evaluate the biological parameters. The optimal development of A. brasiliensis took place at 29 degrees C. The values of T (time of generation - days), R0 and r m at 30 degrees C were, 13.95, 16.25 and 0.20, respectively. The prey consumption of A. brasiliensis was studied at the densities of 5, 10, 20, 40 and 60 leprosis mite females per cage (3 cm in diameter) on citrus fruits at 29 degrees C. The maximum prey, namely 7.6 B. phoenicis females per day, were consumed at a density of 20 leprosis mites. At densities of above 40 leprosis mites per cage, A. brasiliensis oviposits 4.7 eggs per day, in comparison to 2.5 eggs per day at 20 mites per cage.

[Mucoepidermoid carcinoma of the thyroid: a case report and literature review]. / Carcinoma mucoepidermóide de tireóide: relato de caso e revisão da literatura.

The mucoepidermoid carcinoma is a neoplasia that usually occurs at salivary glands, breast, pancreas and gastrointestinal tract. The primary occurrence on thyroid gland is rare and only 33 cases were previously published. Although the majority of cases of mucoepidermoid carcinoma of the thyroid (MECT) show a benign evolution, this paper describes a patient with an aggressive tumor. A literature review over clinical, histopathological, immunohistochemical features and histogenetic origin was discussed.