Breast cancer: the real road of the Brazilian northeast.

Objective: To characterize the clinical and sociodemographic aspects of breast cancer patients undergoing cancer treatment in the State of Maranhão, in a public reference hospital. Methods: Descriptive, correlational and analytical cross-sectional study, conducted between January 2019 and February 2020, at the Tarquínio Lopes Filho State Cancer Hospital. The study population consisted of all women, in first consultation, with breast cancer undergoing chemotherapy, in agreement with the study and with no brain metastasis evidenced. Statistical analysis was performed using SPSS v. 19 software, considering a significance level of 5%. Results: Eighty adult women were part of the study, whose average age was 52.54. Most of the women were born in São Luís, white, housewives, sedentary, married, former smokers, and Catholic. They had technical/specialized training. In the clinical results, the histological type of infiltrative ductal carcinoma predominated, as well as stage III, mastectomy and the doxorubicin-cyclophosphamide-taxol chemotherapy regimen. Conclusion: The knowledge of each regional profile assists health professionals regarding the characterization of a target population and the design of targeted preventive and self-care strategies by managers.

Sixteen years of evolution of human respiratory syncytial virus subgroup A in Buenos Aires, Argentina: GA2 the prevalent genotype through the years.

Human respiratory syncytial virus (HRSV) is the main viral cause of acute lower respiratory tract infections (LRTI) in children worldwide. In recent years, several preclinical trials with vaccine candidates have been reported. It is in this sense that molecular epidemiological studies become important. Understanding viral dispersion patterns before and after the implementation of a vaccine can provide insight into the effectiveness of the control strategies. In this work we analyzed the molecular epidemiology of HRSV-A over a period of sixteen years (1999-2014) in Buenos Aires. By bioinformatic tools we analyzed 169 sequences of the G glycoprotein gene from hospitalized pediatric patients with LRTI. We found that GA2 was the most prevalent genotype (73.35%). GA5 genotype co-circulated in our region until 2009 when it was no longer detected, except in 2011. The recently globally emerging ON1 lineage with a 72-nt duplication increased its frequency to become the only lineage detected in Buenos Aires in 2014. By discrete phylogeographic analysis of global ON1 strains we could determine that Panama could be the location of the MRCA dated June 20, 2010; and this lineage could be introduced in Argentina from Spain in April 2011. This analysis also showed temporary and geographical clustering of ON1 strains observed as phylogenetic clades with strains exclusively associated from a single country, nevertheless among our 44 ON1 strains from three outbreaks (2012-2014) we could also detect posterior reintroductions and circulation from United States, Cuba, South Korea, and Spain. The continuous phylogeographic analysis of one sublineage of Argentine ON1 strains allowed us to establish that there could be a local clustering of some strains even in neighborhoods. This work shows the potential of this type of bioinformatic tools in the context of a future vaccine surveillance network to trace the spread of new genetic lineages in human populations.

Nitrogen and phosphorus discharge of animal origin in the Baixo Vouga: a spatial data analysis.

The livestock production is a strategic and crucial activity for it fixes populations in rural areas, contributing to its conservation, and most importantly because it ensures food production. By producing meat, milk or eggs, this sector contributes to national food self-sufficiency. However, intensive livestock farming activities carry a strong pollution load on the environment, particularly through the emission of nitrogen (N), phosphorus (P), and greenhouse gases (GHG). The Baixo Vouga region in Portugal due to its climatic conditions and soil characteristics holds a high number of livestock production units mainly cattle, poultry and swine. Thus such an activity contributes to a significant portion of the wealth created in this region. This high potential has collided with the existence of environmentally sensitive areas, many of which are protected by European environmental regulations. This work studies the geographical distribution of livestock population of cattle, poultry and swine in the Baixo Vouga region and quantifies its impacts on the environment by calculating the excretion loads of N and P of these species. In the cattle and poultry sectors two clusters or agglomerations are identified, the first in the northern region and the second in the inland region. Moreover, the cattle farming cluster overlaps on vulnerable zones requiring specific monitoring on effluent treatment issues.

LAMP2 as a marker of EBV-mediated B lymphocyte transformation in the study of lysosomal storage diseases.

Following the degradative pathway, vesicles loaded with extracellular material, eventually, dock and fuse with lysosomes, acquiring specific membrane markers of these organelles and acid hydrolases responsible for digest their content. The lysosomal-associated membrane protein 2 (LAMP-2), the best characterized lysosomal membrane protein, is found in late stages of endosome maturation and may be used as a marker of lysosome-associated membranes. Lysosomal storage disorders (LSDs) are described by the absence or deficiency in hydrolase activity leading to substrate accumulation within lysosomal components and to the onset of several diseases. It is known that lymphocytes infected by Epstein-Barr virus (EBV) are able to form cytoplasmic vacuoles, which work as a storage compartment for lysosomal acidic hydrolases. At the present study, we validate the EBV as a transforming agent of B lymphocytes in stability studies of long-term stored samples, since the methods used to keep samples in liquid nitrogen and thaw them have all proven to be efficient in samples frozen for up to 2 years. To confirm and investigate some of the most prevalent LSDs in the South of Brazil-Pompe, Fabry and Gaucher diseases-we first measured the enzymatic activity of α-glicosidase, α-galactosidase, and ß-glicosidase in those cytoplasmic-formed vacuoles and then looked to LAMP-2 immunoreactivity by employing confocal microscopy techniques.

Genetic and phylogenetic analyses of influenza A H1N1pdm virus in Buenos Aires, Argentina.

An influenza pandemic caused by swine-origin influenza virus A/H1N1 (H1N1pdm) spread worldwide in 2009, with 12,080 confirmed cases and 626 deaths occurring in Argentina. A total of 330 H1N1pdm viruses were detected from May to August 2009, and phylogenetic and genetic analyses of 21 complete genome sequences from both mild and fatal cases were achieved with reference to concatenated whole genomes. In addition, the analysis of another 16 hemagglutinin (HA), neuraminidase (NA), and matrix (M) gene sequences of Argentinean isolates was performed. The microevolution timeline was assessed and resistance monitoring of an NA fragment from 228 samples throughout the 2009 pandemic peak was performed by sequencing and pyrosequencing. We also assessed the viral growth kinetics for samples with replacements at the genomic level or special clinical features. In this study, we found by Bayesian inference that the Argentinean complete genome sequences clustered with globally distributed clade 7 sequences. The HA sequences were related to samples from the northern hemisphere autumn-winter from September to December 2009. The NA of Argentinean sequences belonged to the New York group. The N-4 fragment as well as the hierarchical clustering of samples showed that a consensus sequence prevailed in time but also that different variants, including five H275Y oseltamivir-resistant strains, arose from May to August 2009. Fatal and oseltamivir-resistant isolates had impaired growth and a small plaque phenotype compared to oseltamivir-sensitive and consensus strains. Although these strains might not be fit enough to spread in the entire population, molecular surveillance proved to be essential to monitor resistance and viral dynamics in our country.

Non-influence of fetal gender on ductus venosus Doppler flow in the first trimester.

OBJECTIVES: Recent findings have suggested that ductus venosus blood flow may be influenced by fetal gender. The aim of this study was to investigate further the influence of fetal gender on ductus venosus Doppler flow in the first trimester. METHODS: This was a cross-sectional and retrospective study performed between January 1998 and January 2003. A total of 932 fetuses at between 10 and 14 weeks' gestation were included. The following inclusion criteria were used: singleton gestation; crown-rump length between 39 and 84 mm; and absence of fetal anomalies. The following variables of the ductus venosus were evaluated: peak velocity during ventricular systole (S-wave) and diastole (D-wave); nadir during atrial contraction in late diastole (A-wave); pulsatility index for veins (PIV); peak velocity index for veins (PVIV); and time-averaged maximum velocity (TAMXV). RESULTS: Four hundred and forty-eight (48.1%) female and 484 (51.9%) male fetuses were included in the study. Comparing males and females at between 10 and 14 weeks' gestation, there was no statistically significant difference in S-wave, D-wave, A-wave, PIV, PVIV or TAMXV. CONCLUSIONS: Our study suggests that fetal gender does not influence ductus venosus blood flow in the first trimester.

Ductus venosus Doppler velocimetry in the first trimester: a new finding.

OBJECTIVES: To establish reference curves for ductus venosus blood flow velocities during the first trimester and compare them with previously published curves. METHODS: This was a cross-sectional and retrospective study performed between January 1998 and January 2003. The following inclusion criteria were used: singleton pregnancy, velocity measurements taken when the crown-rump length (CRL) was between 34 and 84 mm, absence of fetal anomalies, full-term pregnancy and newborn birth weight appropriate for gestational age. The following variables of the ductus venosus were measured: peak velocity during ventricular systole (S-wave) and diastole (D-wave), nadir during atrial contraction in late diastole (A-wave), time-averaged maximum velocity (TAMXV) and pulsatility index for veins (PIV). RESULTS: A total of 843 fetuses were included. The mean CRL was 62 (range, 34-84) mm. The S-wave, D-wave, TAMXV and PIV were normally distributed, and logarithmic transformation was performed to achieve a normal distribution for the A-wave. S-wave, D-wave and A-wave and TAMXV increased with CRL. PIV increased up to a CRL of 63 mm and decreased thereafter. Regression analysis revealed a significant quadratic relationship between PIV and CRL. CONCLUSIONS: S-wave, D-wave, A-wave velocities and TAMXV in the ductus venosus increase with CRL between 34 and 84 mm. The reference range for PIV has a biphasic pattern, with an initial non-significant increase up to a CRL of 63 mm and a fall thereafter.

An improved and cost-effective methodology for the reduction of autofluorescence in direct immunofluorescence studies on formalin-fixed paraffin-embedded tissues.

Interference by autofluorescence is one of the major shortcomes of immunofluorescence analysis by confocal laser scanning microscopy (CLSM). CLSM requires minimal tissue autofluorescence and reduced unspecific fluorescence background, requisites that become more critical when direct immunofluorescence studies are concerned. To control autofluorescence, different reagents and treatments can be used. Until now, the efficacy of the processes described depended on the tissue type and on the processing technique, no general recipe for the control of autofluorescence being available. Using paraffin sections of archival formalin-fixed murine liver, kidney and pancreas, we have found that previously described techniques were not able to reduce autofluorescence to levels that allowed direct immunofluorescence labelling. In this work, we aimed at improving currently described methodologies so that they would allow reduction of the autofluorescent background without affecting tissue integrity or direct immunofluorescence labelling. We have found that the combination of short-duration, high-intensity UV irradiation and Sudan Black B was the best approach to reduce autofluorescence in highly vascularised, high lipofuscins' content tissues, such as murine liver and kidney, and poorly vascularised, low lipofuscins' content tissues such as the pancreas. In addition, we herein show that this methodology is highly effective in reducing autofluorescent background to levels that allow detection of specific signals by direct immunofluorescence.

Validation of a melasma quality of life questionnaire for Brazilian Portuguese language: the MelasQoL-BP study and improvement of QoL of melasma patients after triple combination therapy.

BACKGROUND: Pigmentation disorders, such as melasma, greatly influence the quality of life (QoL) of affected individuals who usually consider the disorder to be more severe than the objective clinical scores. Several instruments have been successfully developed to evaluate QoL. However, they must be adapted to the target population in terms of language and cultural diversity. The first, specific QoL questionnaire for melasma (MelasQoL) was developed for English speaking patients. OBJECTIVES: To validate the Brazilian Portuguese version of the MelasQoL evaluation questionnaire for patients with melasma (MelasQoL-BP) and to assess the impact of treatment with a triple combination cream (hydroquinone, fluocinolone acetonide and tretinoin) on the QoL of patients with moderate-to-severe melasma. METHODS AND RESULTS: Three hundred individuals from the five Brazilian geographic regions took part in this multicentre study. Their mean age was 42 years and skin phototype distribution was: type II 7.0% of patients, III 23.7%, IV 42.7% and V 22.7%. Melasma Area and Severity Index (MASI), MelasQoL-BP and the short version of the QoL assessment instrument from the World Health Organization (WHOQOL-BREF) were used to assess melasma severity and QoL at baseline. MelasQoL-BP was previously translated and culturally adapted from the English version, with participation of the authors and according to the standards of the World Health Organization (WHO). From the original sample, we randomized150 volunteers to treat melasma and repeated the evaluation after 8 weeks. The analysis of the MelasQoL-BP baseline answers demonstrated an important impact of the disease on skin appearance (65% of patients were bothered all the time or most of the time), frustration (55%), embarrassment (57%) and influence of the disease on interpersonal relationships (42%). Forty-three per cent of patients felt not attractive or even dirty due to their skin condition. MelasQoL-BP results showed significant internal consistency (Cronbach's alpha coefficient 0.919; P < 0.001) and good correlation with MASI scores. After treatment, the global assessment showed good or excellent results in 91.4% of the patients. The clinical outcome was not associated with the initial MASI score (P = 0.814; chi-square), skin colour (P = 0.449; probability ratio) or skin pigmentation (P = 0.814; chi-square). There was also a significant reduction on MelasQoL-BP scores (Wilcoxon test; P < 0.001) after treatment, with the mean +/- SD results shifting from 44.4 +/- 14.9 at baseline to 24.3 +/- 15.5 after treatment. The analysis of the MelasQoL-BP before and after treatment showed an important effect of the impact of treatment on a number of QoL measures. Of note, skin appearance (69.8 vs. 10.1% of patients were bothered all the time or most of the time, respectively), frustration (59.7% vs. 12.2%, respectively), embarrassment (56% vs. 9.3%, respectively) and influence of the disease on interpersonal relationships (35.3% vs. 5.8%, respectively) were greatly improved. CONCLUSIONS: This study demonstrates that MelasQoL-BP is a valid instrument and can be used to evaluate the quality of life and response to melasma treatment in Brazilian patients. The triple combination treatment produced significant results, regarding both clinical severity and quality of life.

Detection of interleukin 10 in cerebrospinal fluid of patients with subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disorder due to persistent measles virus infection, with high level of measles-specific antibodies in cerebrospinal fluid (CSF). To analyze whether such response arises from a TH2-biased response, the authors determined TH1 (interferon [IFN]-gamma) and TH2 (interleukin [IL]-4 and IL-10) cytokines in CSF, taken at diagnosis, of eight SSPE patients (median age, 57.5 month, range 42 to 76 months). All patients presented IL-10 (median 29.3 pg/ml, range 4.3 to 162 pg/ml), but not IL-4 (<10 pg/ml); only one case showed IFN-gamma (162 pg/ml). These results are consistent with a TH2 bias or with a local, anti-inflammatory or neuroprotective mechanism involving IL-10.

Entomophthoramycosis by Conidiobolus coronatus. Report of a case successfully treated with the combination of itraconazole and fluconazole.

Rhinoentomophthoramycosis caused by Conidiobolus coronatus in a 61-year old woman was unsuccessfully treated during 8 years with all the antifungals available in the Brazilian market, including potassium iodide for 1 month, sulfamethoxazole plus trimethoprim for 2 months, amphotericin B, total dose of 1130 mg, cetoconazole, 400 mg/day for 6 months, fluconazole, 200 mg/day, for at least 2 months and, itraconazole, 400 mg/day for 2 months, followed by 200 mg/day for 4 more months. Complete clinical and mycological cure was achieved using itraconazol 400 mg/day in association with fluconazol 200 mg/day during 24 months. After cure she was submitted to plastic surgery to repair her facial deformation. Today she remains clinically and mycologically cured after 59/60 months (5 years!) without any specific antifungal. We thus suggest the use of the combination of itraconazole and fluconazole as an additional option for the treatment of this mycosis.

Relating induced changes in EEG signals to orientation of visual stimuli using the ESI-256 machine.

The focus of this study is to investigate the relations that exist between changes in the orientation of simple visual stimuli displayed to a subject and the induced changes in brain activity recorded as EEG signals. These signals are recorded using the Electric Source Imaging with 256 electrodes (ESI-256). The 256-channel EEG signals of four subjects were measured monopolarly. Each subject was stimulated visually for approximately 7.5 minutes. The stimuli consisted of a series of 300 images depicting four basic orientations of a simple graphical element: a white bar on a black background, with each one of the four orientations (horizontal, vertical, +45 degrees and -45 degrees) shown a total of 75 times in a random order. The notion of missing information under certain orientations is not addressed at this juncture. The EEG signals produced by each subject were recorded in a continuous mode using a sampling rate of 1 kHz. Pre-processing of the raw EEG data obtained consisted of epoching, exclusion of faulty electrodes, and reduction of electro-oculogram (EOG) noise due to eye blinks. Topographical maps displaying brain activities and their individual electrode recordings are used as two different means for assessing these changes. It is important to note that the simplicity of the visual stimuli was considered in view of the massive data collected for interpretation. Our goal is to observe and determine new measures that would allow for the quantification and interpretation of such EEG brain activities. Such findings might prove useful for the later use of more complex stimuli and the potential development of size and orientation independent algorithms in image processing.

Differential expression of and responsiveness to transforming growth factor-beta (TGF-beta) isoforms in hormone-dependent and independent lines of mouse mammary tumors.

Transforming growth factor-beta2 (TGF-beta2) and -beta3 mRNA expressions were studied in ductal hormone-dependent (HD) and -independent (HI) in vivo lines of the medroxyprogesterone acetate (MPA)-induced mammary tumor model in Balb/c mice. MPA treatment of HD tumors induced a significant decrease in TGF-beta2 and -beta3 mRNA levels. Progression to an HI phenotype of ductal tumors was associated with reduced TGF-beta2 and -beta3 expressions, as compared with their HD counterparts. Exogenously added TGF-beta1, -beta2, and -beta3 (1 ng/ml) inhibited the proliferation of primary cultures of epithelial cells from ductal HD and HI tumors. In addition, TGF-beta expression and effects were studied in the other type of MPA-induced mammary tumors, which are of lobular origin and lack steroid hormone receptors and evidence an HI behavior. These lobular HI lines showed TGF-beta2 levels similar to those found in HD lines growing in MPA-treated mice. In contrast, TGF-beta3 mRNA levels were 12- to 20-fold higher than in HD tumors. Primary cultures of lobular HI epithelial cells required either TGF-beta concentrations of 10 ng/ml to show an inhibitory response, or were completely resistant to TGF-beta inhibition. Studies of the molecular mechanisms involved in reduction or loss of TGF-beta responsiveness in lobular HI tumors showed that cell surface type II TGF-beta receptor levels were lower in these tumors than those present in HD tumors. Our results support the hypothesis that TGF-beta could play a role as an autocrine growth inhibitor in HD and HI ductal tumors. Autonomous growth of lobular HI tumors could be favored by undetectable or low TGF-beta1 and -beta2 expressions and by reduced or lost sensitivity of epithelial cells to TGF-beta's antiproliferative effects. However, the extremely high levels of TGF-beta3 expression in lobular HI tumors, in spite of reduced sensitivity to TGF-beta3 inhibitory growth effect in tumor epithelial cells, suggest a net positive role for TGF-beta3 in these tumors.

Ilio-psoas abscess in the neonate.

Ilio-psoas abscess is rare in children and exceptional in the neonate. This report describes a case of idiopathic ilio-psoas abscess in a neonate with no etiologic factor known. The diagnosis was made by ultrasonography and computed axial tomography. The treatment was extraperitoneal surgical drainage and systemic antibiotics.

Representaçöes de pacientes mastectomizadas sobre doença e mutiliaçäo e seu impacto no diagnóstico precoce do câncer de mama / Representation of mastectomized patient about disease and mutilation and impact in diagnosis of breast cancer

A partir de uma nova rotina de atendimento implantada pelos serviços implicados, foram analisadas as representaçöes das pacientes que se submetem a tratamento cirúrgico do câncer de mama. O atendimento multidisciplinar revelou-se importante para a humanizaçäo do atendimento, fato que está presente no discursos da pacientes. Foram atendidas 57 pacientes, no período de 2 anos e meio. Os temores relativos à mutilaçäo e aos danos do tratamento, bem como outras representaçöes sobre a causa da doença, revelaram-se, em muitos casos, impeditivos da procura precoce do tratamento especializado, tendo relevância na prevençäo secundária da enfermidade

Representacoes de pacientes mastectomizadas sobre doenca e mutilacao e seu impacto no diagnostico precoce do cancer de mama

A partir de uma nova rotina de atendimento implantada pelos servicos implicados, foram analisadas as representacoes das pacientes que se submetem a tratamento cirurgico do cancer de mama. O atendimento multidisciplinar revelou-se importante para a humanizacao do atendimento, fato que esta presente no discurso das pacientes. Foram atendidas 57 pacientes, no periodo de 2 anos e meio. Os temores relativos a mutilacao e aos danos do tratamento, bem como outras representacoes sobre a causa da doenca, revelaram-se, em muitos casos, impeditivos da procura precoce do tratamento especializada, tendo relevancia na prevencao secundaria da enfermidade.

The tyrosine kinase activity of the epidermal-growth-factor receptor is necessary for phospholipase A2 activation.

We have previously reported that epidermal growth factor (EGF) activates phospholipase A2 (PLA2) independently of phospholipase C (PLC) in renal mesangial cells. In this study we use NIH 3T3 cell lines transfected with the normal EGF receptor (HER14 cells) or with EGF receptor defective in tyrosine kinase activity (K721A cells), to determine whether the intrinsic tyrosine kinase activity of the EGF receptor is required for the PLC-independent activation of PLA2. Intact cells were preincubated with EGF or other ligands, and then PLA2 activity was assayed in cell-free extracts with 1-stearoyl-2-[14C]arachidonyl phosphatidylcholine as the substrate. In HER14 cells, EGF increased PLA2 activity by 226 +/- 30%, and the tumour promoter phorbol myristate acetate (PMA) increased activity by 223 +/- 30%. The effect of EGF was not mediated through protein kinase C (PKC), whose activation by EGF requires tyrosine kinase activity, since raising intracellular Ca2+ alone with the Ca2+ ionophore A23187 did not mimic its effect, and the effect of EGF persisted in PKC-down-regulated cells. In K721A cells EGF was ineffective, whereas PMA was still active. Furthermore, in intact HER14 cells prelabelled with [14C]arachidonate, EGF-stimulated release of [14C]arachidonic acid was synergistic with A23187, but was unaccompanied by a rise in [14C]diacylglycerol. EGF had no effect on [14C]arachidonic acid release in intact K721A cells. We conclude that the tyrosine kinase activity of the EGF receptor is necessary for the PLC-independent stimulation of PLA2 by EGF.

[Pitted keratolysis of hyperkeratotic form and isolation of the etiologic agent: Corynebacterium sp]. / Queratólisis en hoyuelos (pitted keratolysis) a forma hiperqueratósica y aislamiento del agente etiológico: Corynebacterium sp.

Two cases of "pitted keratolysis" with a very accentuated plantar hyperkeratosis, and the isolation on chocolate thelurite agar of the presumptive etiologic agent, Corynebacterium sp., is presented. In order to keep permanently in mind, for a proper diagnosis, the original description of the disease as "keratoma plantare sulcatum" (Castellani, 1910), we are proposing to distinguish two different clinical forms: The hyperkeratotic one and the common or usual form of "pitted keratolysis" with keratolysis as the main sign. The prosecution of our biochemical studies with a significant number of strains isolated from both "pitted keratolysis" and from classical erythrasma cases, will surely permit us to definitively determine if all of them should or not be assimilated to Corynebacterium minutissimum.