Grape is the most consumed nectar in Brazil and a relatively expensive beverage. Therefore, it is susceptible to fraud by substitution with other less expensive fruit juices. Adulterations of grape ...nectars by the addition of apple juice, cashew juice, and mixtures of both were evaluated by using low-field nuclear magnetic resonance (LF-NMR) and supervised multivariate classification methods. Two different approaches were investigated using one-class (only unadulterated samples (UN) were modeled) and multiclass (three classes were modeled: UN, adulterated with cashew (CAS), and adulterated with apple (APP)) strategies. For the one-class approach, soft independent modeling of class analogy (SIMCA), one-class partial least squares (OCPLS), and data-driven SIMCA (DD-SIMCA) models were built. For the multiclass approach, partial least squares discriminant analysis (PLS-DA) and multiclass SIMCA models were built. The results obtained demonstrated good performances by all the one-class methods with efficiency rates higher than 93%. For the multiclass approach, the classification of samples containing only one type of adulterant presented efficiencies higher than 90% and 97% using SIMCA and PLS-DA, respectively. The classification of samples containing blends of two adulterants was satisfactory for the CAS class, but not for the APP class when applying PLS-DA. Nevertheless, multiclass SIMCA did not provide satisfactory predictions for either of these two classes.
A sepse é descrita como uma disfunção orgânica ameaçadora à vida secundária à resposta desregulada do organismo a uma infecção, e é responsável por uma alta e crescente taxa de internação hospitalar ...no Brasil e no mundo. Apesar da diminuição da mortalidade ao longo do tempo, efeitos da doença a longo prazo como infecções secundárias e mortes tardias têm sido observadas. A sepse caracteriza-se pela liberação de mediadores inflamatórios e posterior imunossupressão compensatória, e o distúrbio na homeostase pode causar danos às células e órgãos levando a um estado mais grave da doença. Os linfócitos T reguladores (Tregs) são células responsáveis pela tolerância periférica e modulação de processos inflamatórios e são essenciais na imunossupressão observada na sepse. Este trabalho teve por objetivo estudar a relação entre a atividade imunológica (quantificação de Tregs, monócitos e citocinas inflamatórias) e a susceptibilidade a novas infecções e mortalidade em pacientes sépticos admitidos na Unidade de Emergência do HC-FMRP-USP. Foram incluídos 33 pacientes sépticos e 34 controles saudáveis, entre outubro de 2014 e novembro de 2015. Os pacientes foram acompanhados durante a internação na admissão (D0), D2, D7, D14, D21 e D28, e 12 pacientes retornaram para avaliação pelo menos três meses após a alta. Os pacientes tiveram porcentagens de Treg em linfócitos CD4+ elevados em relação aos controles nos momentos D2 e retorno (p = 0,0004), sendo que no D2 pacientes que desenvolveram complicação infecciosa tiveram porcentagens significativamente menores que os que não desenvolveram complicação (p = 0,0015). Além disso, porcentagens altas de Treg na admissão (D0) correlacionaram-se inversamente com o tempo de internação dos pacientes sobreviventes (p = 0,0271). Valores absolutos de Treg nos pacientes estiveram significativamente elevados no retorno em relação à admissão (p = 0,0074). Pacientes no retorno tiveram maior porcentagem de monócitos CD163+ em relação aos controles (p = 0,036). Pacientes na admissão tiveram menor porcentagem demonócitos HLA-DR+ em relação aos controles e aos pacientes no retorno (p = 0,0057). Pacientes tiveram valores de IL-6, IL-8, IL-10 e ST2 superiores em relação aos controles em diversos momentos da internação e retorno (p < 0,0001, p < 0,0001, p = 0,0030 e p < 0,0001, respectivamente). Valores de ST2 na admissão correlacionaram-se com o escore SOFA (p = 0,0252), tempo de internação (p = 0,0105), presença de complicação infecciosa (p = 0,0356) e mortalidade (p = 0,0114) dos pacientes. Valores de IL-8 na admissão também se correlacionaram com a presença de complicação infecciosa (p = 0,0387). Podemos inferir, portanto, que apesar de uma inflamação exacerbada já na admissão dos pacientes, evidenciada por altos valores de citocinas inflamatórias, há um aumento posterior de células Treg, imunorreguladoras, no D2, e o mesmo foi benéfico em relação à recuperação mais rápida dos pacientes e instalação de uma nova infecção. Porém, a imunossupressão continua sendo exibida mesmo após a alta dos pacientes, como podemos observar com a alta porcentagem de Tregs e monócitos CD163+ e valores de IL-10 nos pacientes em retorno em relação aos controles. Além disso, muitos dos pacientes sobreviventes à primeira internação foram internados novamente, e alguns deles foram a óbito no ano seguinte.
Sepsis is defined by a life-threatening organ dysfunction caused by a dysregulated host response to infection, and it is responsible for a high and increasing rate of hospital admission in Brazil and worldwide. Despite the decrease in mortality over time, long-term disease effects such as secondary infections and late deaths have been observed. Sepsis is characterized by the release of inflammatory mediators and subsequent compensatory immunosuppression, and the homeostasis disorder can cause damage to cells and organs leading to a more severe disease state. Regulatory T lymphocytes (Tregs) are cells responsible for peripheral toleran ce and modulation of inflammatory processes and are essential in the immunosuppression observed in sepsis. This study aimed to investigate the relationship between immunological activity (quantification of Tregs, monocytes and inflammatory cytokines) and susceptibility to new infections and mortality in septic patients admitted to the HC-FMRP-USP Emergency Unit. Thirty-three septic patients and 34 healthy controls were included between October 2014 and November 2015. Patients were followed up at admission (D0) and during hospitalization at D2, D7, D14, D21 and D28, and 12 patients returned for evaluation at least three months after discharge. Patients had higher Treg percentages on CD4 + lymphocytes than had controls at D2 and on return (p = 0.0004), whereas in D2 patients who developed infectious complications had significantly lower percentages than those who did not develop complications (p = 0.0015). In addition, high percentages of Treg at admission (D0) correlated inversely with the length of hospital stay of surviving patients (p = 0.0271). Absolute values of Treg in patients were significantly elevated in the return relative to admission (p = 0.0074). Patients on return had a higher percentage of CD163 + monocytes than controls (p = 0.036). Patients on admission had a lower percentage of HLA-DR+ monocytes than controls and patients on return (p = 0.0057). Patients had higher IL-6, IL-8, IL-10 and ST2 levels than controls at various times ofhospitalization and return (p < 0.0001, p < 0.0001, p = 0.0030 and p < 0.0001, respectively). ST2 values at admission were correlated with SOFA score (p = 0.0252), length of hospital stay (p = 0.0105), presence of infectious complication (p = 0.0356) and mortality (p = 0.0114). IL-8 values at admission also correlated with the presence of infectious complication (p = 0.0387). We can infer, therefore, that despite exacerbated inflammation as soon as at the admission of the patients, demonstrated by high levels of inflammatory cytokines, there is a posterior increase of immunoregulatory Treg cells at D2, and that was beneficial in relation to the faster recovery of the patients and setting up of new infection. However, immunosuppression continues to appear even after discharge of patients, as can be observed with the high percentage of CD163 + monocytes, Tregs and L-10 levels in patients on return compared to controls. In addition, many of the patients surviving the first hospitalization were hospitalized again, and some of them died the following year.
A sepse é responsável por uma alta taxa de internação hospitalar e morbimortalidade. Devido à gravidade do quadro clínico e às limitações dos métodos tradicionais para identificação e isolamento ...bacteriano, é recomendado o início empírico de antimicrobiano(s) de largo espectro. O desenvolvimento da biologia molecular, particularmente da reação em cadeia da polimerase (PCR), tornou possível o diagnóstico rápido de agentes infecciosos. Entretanto, devido à diversidade dos possíveis agentes etiológicos na sepse, a utilização da PCR com primers específicos para cada agente se torna pouco prática. Com a PCR de largo espectro é possível que em uma só reação se identifique qualquer bactéria, possibilitando um tratamento precoce e direcionado. Desta forma, este trabalho teve como objetivo avaliar o papel da PCR de largo espectro no diagnóstico etiológico de pacientes com sepse e a comparação desta técnica com os métodos tradicionais de cultura. Foram incluídos 74 pacientes com diagnóstico de sepse atendidos na Unidade de Emergência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto USP e 14 voluntários sadios. Foi realizada a extração do DNA do soro, plasma e buffy-coat dos pacientes, seguida da realização da PCR de largo espectro com dois diferentes pares de primers, e sequenciamento das amostras positivas. Dos 74 pacientes, 39 (53%) eram homens; a média de idade foi 55 ± 19 anos; 37 (50%) tiveram sepse grave e 37 (50%) choque séptico; e a mortalidade foi 51%. A maioria das infecções primárias teve origem respiratória (66%), seguida de infecções gênito-urinárias (20%). A hemocultura foi positiva em 22 (30%) pacientes, e sua positividade foi significativamente maior em pacientes mais velhos (p< 0,05) e com valores mais altos de proteína C reativa (CRP) (p< 0,05). A PCR de largo espectro foi positiva em 44 (59%) pacientes considerando os dois pares de primers, sendo sua positividade significativamente maior que a da hemocultura (p< 0,001). Para o par Bak11W/Bak2 ela foi positiva em 25 (34%) pacientes, e para o par Taf/Tar, em 29 (39%) pacientes. Em relação às frações do sangue, amostras de 24 pacientes foram positivas na fração soro; 22 na fração plasma; e 18 na fração buffy-coat. Nenhuma característica clínica ou demográfica dos pacientes influenciou a positividade da PCR de largo espectro. A PCR de largo espectro foi negativa em todas as frações do sangue dos voluntários sadios. A sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo da PCR foram 59%, 100%, 100% e 32%, respectivamente. Em 40 (54%) pacientes os resultados da PCR e hemocultura foram concordantes. O coeficiente de concordância kappa obtido foi 0,147 (p = 0,131). Em relação ao sequenciamento, em 21 amostras de 16 pacientes foi possível identificar um agente etiológico. As bactérias mais detectadas foram Escherichia coli (3), Enterococcus sp. (2), Staphylococcus sp. (2) e Ralstonia sp. (2). Em apenas dois pacientes as amostras tiveram a mesma espécie bacteriana detectada na hemocultura e PCR de largo espectro (E. coli e Streptococcus pneumoniae). Em resumo, a PCR de largo espectro foi mais sensível do que a hemocultura na identificação bacteriana em pacientes com sepse atendidos em um Hospital de Emergência
Sepsis is responsible for a high rate of hospitalization and mortality. Due to the severity of clinical presentation and limitation of traditional methods for bacterial identification and isolation, it is recommended to initiate empirically broad-spectrum antimicrobial treatment. The development of molecular biology, particularly the polymerase chain reaction (PCR), enabled to realize a rapid diagnosis of infectious agents. However, due to the diversity of possible etiologic agents in sepsis, the use of PCR with specific primers for each agent becomes impractical. With the broad-range PCR, it is possible, in a single reaction, to identify any bacteria, allowing an early and directed treatment. Thus, this study aimed to evaluate the role of broad-range PCR in the etiologic diagnosis of patients with sepsis and compare this technique with traditional methods of culture. Seventy-four patients with sepsis admitted to the Emergency Unit of Clinical Hospital of Ribeirão Preto Medical School USP and 14 controls were included in the study. DNA from serum, plasma and buffy-coat were extracted from all patients and controls. Broad-range PCR was performed in all samples, followed by DNA sequencing of the amplicons. Out of 74 patients, 39 (53%) were male, mean age was 55 ± 19 years old; 37 (50%) patients had severe sepsis and 37 (50%) septic shock; the mortality rate was 51%. Most of primary infections were from respiratory tract (66%), followed by urinary tract infection (20%). Blood culture was positive in 22 (30%) patients, and its positivity was greater in older patients (p< 0,05) and patients with higher levels of C reactive protein (CRP) (p< 0,05). Broad-range PCR was positive in 44 (59%) patients, when considering both pairs of primers, and was significantly increased compared to blood culture positivity (p< 0,001). Broad-range PCR using Bak11W/Bak2 primers was positive in 25 (34%) patients, and using Taf/Tar primers, in 29 (39%) patients. Related to blood fractions, samples from 24 patients were positive in serum; 22 in plasma fraction; and 18 in buffy-coat. None of clinical and demographic characteristics influenced the broad-range PCR positivity. The sensitivity, specificity, positive predicted value and negative predictive value, when considered healthy persons as negative control, were 59%, 100%, 100% and 32%, respectively. In 40 (54%) patients, blood culture and PCR results were concordant. The concordance coefficient kappa obtained was 0,147 (p = 0,131). Regarding to etiologic agents, in 21 samples, from 16 patients, a bacteria was identified by sequencing. The most common bacteria were Escherichia coli (3), Enterococcus sp. (2), Staphylococcus sp. (2) and Ralstonia sp. (2). In only two patients, the same bacterial species were identified in both, blood culture and broad-range PCR (E. coli e Streptococcus pneumoniae). In conclusion, broad-range PCR was more sensitive than blood culture for bacterial identification in septic patients admitted to an Emergency Unit
Sepsis is an overwhelming systemic inflammation resulting from an uncontrolled infection that causes extensive tissue damage, organ dysfunction and eventually death. A growing body of evidence ...indicates that impaired neutrophil migration to the site of infection is associated with poor outcome in sepsis. Here we show that galectin-3 (Gal-3), an endogenous glycan-binding protein, plays a critical role in sepsis outcome. We found that serum Gal-3 concentration increased in patients with septic shock and mice undergoing sepsis induced by cecal ligation and puncture (CLP). Mice deficient in Gal-3 (Gal-3 KO) are more resistant to sepsis induced by CLP, showing lower levels of biochemical markers and neutrophil infiltration for organ injury/dysfunction than those observed in wild-type mice (WT). Furthermore, Gal-3 KO mice show an increased number of neutrophils in the primary focus of infection and reduced bacterial loads in the peritoneal cavity, blood, and lungs. Mechanistically, blood neutrophils from septic mice show higher levels of surface-bound Gal-3 than neutrophils from naive mice. The deficiency of Gal-3 was associated with increased rolling and adhesion of these cells in mesenteric venules. Our results indicate that Gal-3, secreted during sepsis, inhibits neutrophil migration into the infectious focus, which promotes the bacterial spread and worsens the outcome of sepsis.
OBJETIVO: Avaliar o estado nutricional de ferro, a prevalência de anemia e fatores associados, em crianças de 6 a 24 meses frequentadoras de creche pública em Cascavel, Região Oeste do Paraná, ...Brasil. MÉTODOS: O estudo transversal foi realizado com amostra aleatória de 256 crianças. A coleta de dados (questionário, medidas antropométricas e amostras de sangue) ocorreu de julho a setembro de 2007. A deficiência de ferro foi avaliada em termos de transferrina, hemoglobina, volume corpuscular médio, ferro sérico e eosinófilos. Na análise estatística dos dados foram obtidas as odds ratio bruta e ajustada (regressão logística), bem como os respectivos níveis de significância (p-valor). Para identificar diferenças significativas entre as medidas quantitativas, adotou-se a Análise de Variância e o teste de comparação múltipla de Tukey. RESULTADOS: A prevalência da anemia foi de 29,7%, sendo que 77,3% das amostras apresentaram baixa concentração de ferro. A antropometria não apontou deficiência de macronutrientes, porém mostrou obesidade acima dos índices médios. Os fatores associados à anemia e à deficiência de ferro foram: doenças frequentes na família (OR=10,02), condições de moradia (OR=5,05), tempo de creche (OR=3,05), número de moradores na residência (OR=2,83) e falta de saneamento (OR=2,20). CONCLUSÃO: A prevalência de anemia e a elevada deficiência de ferro detectada evidenciam um grave problema de saúde pública entre os pré-escolares do município de Cascavel, Paraná. Apesar da amplitude do problema, a anemia não está sendo reconhecida, prevenida e tratada adequadamente. Neste estudo são sugeridas algumas possíveis intervenções.
Sepsis is a severe syndrome that arises when the host response to an insult is exacerbated, leading to organ failure and frequently to death. How a chronic infection that causes a prolonged Th1 ...expansion affects the course of sepsis is unknown. In this study, we showed that mice chronically infected with
were more susceptible to sepsis induced by cecal ligation and puncture (CLP). Although
-infected mice exhibited efficient control of the bacterial burden, they showed increased mortality compared to the control groups. Mechanistically, chronic
infection induces the suppression of Th2 lymphocytes via
-repressive methylation and simultaneously induces long-lived IFN-γ-producing CD4
T lymphocytes, which promotes systemic inflammation that is harmful during CLP. Chronic
infection intensifies local and systemic Th1 cytokines as well as nitric oxide production, which reduces systolic and diastolic arterial blood pressures after sepsis induction, thus predisposing the host to septic shock. Blockade of IFN-γ prevented arterial hypotension and prolonged the host lifespan by reducing the cytokine storm. Interestingly, these data mirrored our observation in septic patients, in which sepsis severity was positively correlated to increased levels of IFN-γ in patients who were serologically positive for
. Collectively, these data demonstrated that chronic infection with
is a critical factor for sepsis severity that needs to be considered when designing strategies to prevent and control the outcome of this devastating disease.
OBJETIVO: Analisar a distribuição dos diagnósticos de enfermagem presentes em adultos de uma clínica de hemodiálise de Petrópolis - Rio de Janeiro. MÉTODOS: Estudo quantitativo do tipo transversal, ...de caráter exploratório e descritivo. Foram avaliados 20 pacientes nos meses de abril e maio de 2006. Os instrumentos de coleta de dados foram: roteiro de entrevista e exame físico. RESULTADOS: Verificou-se que metade eram mulheres, sendo a maioria casada, com média de 2 filhos. Foram identificados 16 diagnósticos de enfermagem, quatro desses acima do percentil 75, são eles: Risco de infecção; Perfusão tissular ineficaz: renal; Padrão de sono perturbado e Intolerância à atividade. CONCLUSÃO: O estudo proporcionou maior conhecimento da realidade desses pacientes, contribuindo para uma possível implementação de ações de enfermagem mais eficientes para a solução dos problemas identificados.
OBECTIVE: to analyze the nursing diagnoses present in adults from a hemodialysis clinic in Petrópolis - Rio de Janeiro. METHODS: This is a cross-sectional, exploratory and descriptive study. Twenty patients were evaluated from April to May 2006. The data collection instruments used were: Interview and physical examination. RESULTS: half the patients were women, most were married, and had, in average, two children. Sixteen nursing diagnosis were identified, four of which were above the 75 percentile: Risk of infection; ineffective tissue perfusion: renal; Disturbed sleep pattern and activity intolerance. CONCLUSION: The study provided better knowledge about the reality of patients' lifestyle, thus contributing with the implementation of a more efficient nursing action in order to solve specific problems.
OBJETIVO: Analizar la distribución de los diagnósticos de enfermería presentes en adultos de una clínica de hemodiálisis de Petrópolis - Rio de Janeiro. MÉTODOS: Se trata de un estudio cuantitativo de tipo transversal, de carácter exploratorio y descriptivo. Fueron evaluados 20 pacientes en los meses de abril y mayo del 2006. Los instrumentos de recolección de datos fueron: una guía de entrevista y examen físico. RESULTADOS: Se verificó que la mitad eran mujeres, siendo la mayoría casadas, con un promedio de 2 hijos. Se identificaron 16 diagnósticos de enfermería, cuatro de ellos encima del percentil 75, que son: Riesgo de infección; Perfusión tisular ineficaz: renal; Patrón de sueño perturbado e Intolerancia a la actividad. CONCLUSIÓN: El estudio proporcionó mayor conocimiento de la realidad de esos pacientes, contribuyendo a una posible implementación de acciones de enfermería más eficientes para la solución de los problemas identificados.
A series of indeno1,2-bindole-9,10-dione derivatives were synthesized as human casein kinase II (CK2) inhibitors. The most potent inhibitors contained a N 5-isopropyl substituent on the C-ring. The ...same series of compounds was found to also inhibit the breast cancer resistance protein ABCG2 but with totally different structure–activity relationships: a N 5-phenethyl substituent was critical, and additional hydrophobic substituents at position 7 or 8 of the D-ring or a methoxy at phenethyl position ortho or meta also contributed to inhibition. The best ABCG2 inhibitors, such as 4c, 4h, 4i, 4j, and 4k, behaved as very weak inhibitors of CK2, whereas the most potent CK2 inhibitors, such as 4a, 4p, and 4e, displayed limited interaction with ABCG2. It was therefore possible to convert, through suitable substitutions of the indeno1,2-bindole-9,10-dione scaffold, potent CK2 inhibitors into selective ABCG2 inhibitors and vice versa. In addition, some of the best ABCG2 inhibitors, which displayed a very low cytotoxicity, thus giving a high therapeutic ratio, and appeared not to be transported, constitute promising candidates for further investigations.
Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities ...collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience.
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