Diagnostic accuracy of thromboelastometry and its correlation with the HPLC-MS/MS quantification test.

The aim of the study was to evaluate the diagnostic accuracy of thromboelastometry for assessing rivaroxaban concentrations. The accuracy of thromboelastometry was compared with the high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method, which is the gold standard for drug plasma monitoring (the reference standard). Forty-six clinically stable patients were treated with 10, 15, or 20 mg of rivaroxaban once daily (OD group) or 15 mg twice a day (BID group) (no particular indication for treatment). Patient samples were collected 2 h after the use of the medication (peak) and 2 h before the next dose (trough). The rivaroxaban plasma concentrations were determined via HPLC-MS/MS, and thromboelastometry was performed using a ROTEM® delta analyzer. There were significant prolongations in clotting time (CT) for the 10, 15, and 20 mg of rivaroxaban treatments in the OD groups. In the 15 mg BID group, the responses at the peak and trough times were similar. At the peak times, there was a positive correlation between the plasma concentration of rivaroxaban and CT (Spearman correlation rho=0.788, P<0.001) and clot formation time (rho=0.784, P<0.001), and a negative correlation for alpha angle (rho=-0.771, P<0.001), amplitude after 5 min (rho=-0.763, P<0.001), and amplitude after 10 min (rho=-0.680, P<0.001). The CT presented higher specificity and sensitivity using the cut-off determined by the receiver characteristics curve. ROTEM has potential as screening tool to measure possible bleeding risk associated with rivaroxaban plasma levels.

Diagnostic accuracy of thromboelastometry and its correlation with the HPLC-MS/MS quantification test

The aim of the study was to evaluate the diagnostic accuracy of thromboelastometry for assessing rivaroxaban concentrations. The accuracy of thromboelastometry was compared with the high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method, which is the gold standard for drug plasma monitoring (the reference standard). Forty-six clinically stable patients were treated with 10, 15, or 20 mg of rivaroxaban once daily (OD group) or 15 mg twice a day (BID group) (no particular indication for treatment). Patient samples were collected 2 h after the use of the medication (peak) and 2 h before the next dose (trough). The rivaroxaban plasma concentrations were determined via HPLC-MS/MS, and thromboelastometry was performed using a ROTEM® delta analyzer. There were significant prolongations in clotting time (CT) for the 10, 15, and 20 mg of rivaroxaban treatments in the OD groups. In the 15 mg BID group, the responses at the peak and trough times were similar. At the peak times, there was a positive correlation between the plasma concentration of rivaroxaban and CT (Spearman correlation rho=0.788, P<0.001) and clot formation time (rho=0.784, P<0.001), and a negative correlation for alpha angle (rho=−0.771, P<0.001), amplitude after 5 min (rho=−0.763, P<0.001), and amplitude after 10 min (rho=−0.680, P<0.001). The CT presented higher specificity and sensitivity using the cut-off determined by the receiver characteristics curve. ROTEM has potential as screening tool to measure possible bleeding risk associated with rivaroxaban plasma levels.

Therapeutic salivary monitoring of IV busulfan in patients undergoing hematopoietic stem cell transplantation: a pilot study.

Individual therapeutic monitoring of busulfan (BU) minimizes its toxicity and improves the therapeutic outcomes during hematopoietic stem cell transplantation (HSCT). For individual dose adjustment, several blood collections are performed that are uncomfortable for patients. The aim of this pilot study was to validate a laboratory method for quantification of BU in saliva and to present the results obtained using this protocol in HSCT patients. We performed analyses of selectivity, precision and accuracy of saliva with standard concentrations of BU using ultra-high-performance liquid chromatography with diode array detection. We also determined salivary and plasmatic concentrations of BU in six HSCT patients. Saliva exhibited excellent selectivity, precision and accuracy for quantification of BU. In the patient samples, significant correlations were noted between plasmatic and salivary concentrations of BU (r=0.97, P<0.001 in the test dose; r=0.93, P<0.001 in the adjusted dose). Passing &Bablok regression revealed good agreement between the two methods (R2=0.956 for test dose; R2=0.927 for adjusted dose). In conclusion, the saliva is safe for laboratory BU measurement. The good agreement with plasma encourages further clinical studies using saliva for BU therapeutic monitoring.

Utilização do yacon ( Smallanthus sonchifolius ) na proteção contra colonização intestinal de frangos de corte infectados por Salmonella Enteritidis / Use of yacon (Smallanthus sonchifolius) protect against intestinal colonization of broilers infectes by Salmonella Enteritidis]

Os frutanos do tipo inulina são oligossacarídeos que favorecem a multiplicação de determinados gêneros bacterianos no intestino, promovendo um efeito prebiótico. Este trabalho avaliou o efeito da inulina extraída de raízes de yacon (Smallanthus sonchifolius) sobre a colonização intestinal de frangos de corte experimentalmente infectados por Salmonella Enteritidis. Sessenta frangos de corte com um dia de idade foram divididos em três grupos de tratamento, com duas repetições, criados até 21 dias. As aves do grupo yacon receberam 100mg de inulina/dia, via oral, por três dias consecutivos. No sétimo dia de vida, as aves tratadas e o controle positivo foram desafiados pela via oral com uma cultura de S. Enteritidis. Não foram observadas diferenças de desempenho zootécnico entre os grupos. O índice de infectividade das aves suplementadas com yacon foi menor até o sexto dia após o desafio, mas, ao término do experimento, foi superior ao controle positivo. Os dados deste trabalho demonstram que o uso da inulina nos três primeiros dias de vida promoveu uma redução da colonização intestinal dos frangos por Salmonella Enteritidis na primeira semana após o desafio. Novos estudos são necessários para determinar a dose e o tempo de tratamento ideal para um efeito protetor de maior duração.(AU)

The fructan inulin-type oligosaccharides favor the multiplication of some bacterial genera in the intestine, promoting a prebiotic effect. This study evaluated the effect of inulin extracted from yacon roots (Smallanthus sonchifolius) on intestinal colonization of broilers experimentally infected with Salmonella Enteritidis. Sixty-one day old chicks were grouped into three treatments, with two replicates, and reared until 21 days. Birds in the yacon group received 100mg of inulin/day orally for three consecutive days. On the seventh day of life the treated birds and the positive control were challenged orally with a culture of S. Enteritidis. There were no differences between groups in live performance. The infectivity index of the chicks supplemented with yacon was lower until the sixth day after the challenge, but at the end of the experiment it was higher than the positive control. Data from this study show that the use of inulin during the first 3 days of life caused a reduction of intestinal colonization of chickens by Salmonella Enteritidis in the first week after challenge. Further studies are needed to determine the dose and the ideal time of treatment necessary for a longer protective effect.(AU)

The First population structure and comparative genomics analysis of Mycobacterium africanum strains from Ghana reveals higher diversity of Lineage 5.

OBJECTIVE/BACKGROUND: Mycobacterium africanum (MAF) remains an important TB causing pathogen in West Africa; however, little is known about its population structure and actual diversity which may have implications for diagnostics and vaccines. We carried out comparative genomics analysis of candidate Mycobacterium tuberculosis (MTB) and MAF using whole genome sequencing. METHODS: Clinical MTB complex strains (n=187) comprising L4 (n=22), L5 (n=126), and L6 (n=39) isolated over 8years from Ghana were whole genome sequenced. The reads were mapped onto a reference genome for phylogenetic and functional genomics analysis. A maximum likelihood tree with 100 bootstraps was constructed from the single nucleotide polymorphisms (SNPs) found using RAxML and clustered with hierBAPS. A total of 147 (18 L4, 36 L6, and 93 L5) of the genomes were de novo assembled and annotated for comparative pangenome analysis using Roary. RESULTS: The population structure of MAF revealed at least five clusters of L5 as compared to three for L6. We also identified a group of three multi-drug-resistants (MDRs) within a single cluster of L5 strains from Southern Ghana isolated in 2013. Among the global collection of MTB complex, there were four Ghana-specific L5 clusters of which one (L5.1.1) had traits of clonal expansion. From the 5947pan genes extracted from the collection, 3215 (54.1%) were core to all the 147 genomes whereas 719 (12.1%) were found in single genomes. Most of the variable genes were PE-PGRS/PPE (1,281) duplicates of other genes (431). The genome degradation was more pronounced in Lineages 4 and 6 as compared to Lineage 5. We identified the absence of some unique genes among specific lineages and/or clades with possible clinical implications. For example, mpt64 and mlaD encoding respectively an immunogenic protein and a mammalian cell entry protein were missing from all L6 genomes. In addition, all L5 strains had an amino acid substitution I43N within the mpt64 gene. Analysis of SNPs within some genes encoding proteins for substrate metabolism, ion transport and secretory systems showed higher proportion of SNPs among L6 compared to L5 and L4. We also identified a number of lineage/sublineage specific SNPs and indels that may be utilized in rapid PCR based genotyping of MTB complex. CONCLUSION: This work emphasizes on the possibility that the mpt64-based rapid diagnostic kit would not be effective in MAF endemic settings. More mutations in ESAT-6 secretory system of MAF compared to MTB sensu stricto can affect efficacy of ESAT-6-based vaccines in the future.

Temporal coherence among tropical coastal lagoons: a search for patterns and mechanisms.

Temporal coherence (i.e., the degree of synchronicity of a given variable among ecological units within a predefined space) has been shown for several limnological features among temperate lakes, allowing predictions about the structure and function of ecosystems. However, there is little evidence of temporal coherence among tropical aquatic systems, where the climatic variability among seasons is less pronounced. Here, we used data from long-term monitoring of physical, chemical and biological variables to test the degree of temporal coherence among 18 tropical coastal lagoons. The water temperature and chlorophyll-a concentration had the highest and lowest temporal coherence among the lagoons, respectively, whereas the salinity and water colour had intermediate temporal coherence. The regional climactic factors were the main factors responsible for the coherence patterns in the water temperature and water colour, whereas the landscape position and morphometric characteristics explained much of the variation of the salinity and water colour among the lagoons. These results indicate that both local (lagoon morphometry) and regional (precipitation, air temperature) factors regulate the physical and chemical conditions of coastal lagoons by adjusting the terrestrial and marine subsidies at a landscape-scale. On the other hand, the chlorophyll-a concentration appears to be primarily regulated by specific local conditions resulting in a weak temporal coherence among the ecosystems. We concluded that temporal coherence in tropical ecosystems is possible, at least for some environmental features, and should be evaluated for other tropical ecosystems. Our results also reinforce that aquatic ecosystems should be studied more broadly to accomplish a full understanding of their structure and function.

IL-10 and TGF-beta immunoregulatory cytokines rather than natural regulatory T cells are associated with the resolution phase of Vogt-Koyanagi-Harada (VKH) syndrome.

The pro-inflammatory cytokines play a critical role in the initiation and propagation of ocular autoimmune diseases. Regulation of these cytokines is generally mediated by the immunoregulatory cytokine such as IL-10 or TGF-beta. In this study, we investigated the immunoregulatory cytokine profile and frequency of natural regulatory T cells (nTregs) in patients with Vogt-Koyanagi-Harada (VKH). We obtained the peripheral blood mononuclear cells (PBMC) from patients with VKH and healthy controls. The cytokine profile from supernatants of PBMC cultured with or without phytohaemagglutinin (PHA) was measured by ELISA, the percentage of CD4(+) Foxp3(+) and CD25(high)Foxp3(+) T regulatory cells were analysed by flow cytometry, and the transcriptional level of Foxp3 expression was analysed by real-time quantitative PCR. The immunoregulatory cytokines, TGF-beta and IL-10, increased in patients with VKH in the inactive stage of the disease. We observed no significant difference in the CD4(+) Foxp3(+) and CD25(high)Foxp3(+) T cells as well as no reduction in FOXP3 mRNA expression in the patients with VKH when compared to healthy controls. We showed in our work, an increase in IFN-gamma secretion by PBMC of patients with VKH in the active stage of the disease when compared to healthy controls and patients in the inactive stage. Our data suggest that IL-10 and TGF-beta cytokines, rather than nTregs are associated with the resolution phase of the disease and may have a more relevant role in controlling this disease.

Wrestling with typology: penetrating the "black box" of managed care by focusing on health care system characteristics.

The health care system has undergone a fundamental transformation undermining the usefulness of the typology of the health maintenance organization, the independent practice association, the preferred provider organization, and so forth. The authors present a new approach to studying the health care system. In matrix form, they have identified a set of organizational and delivery characteristics with the potential to influence outcomes of interest, such as access to services, quality, health status and functioning, and cost. The matrix groups the characteristics by domain--financial features, structure, care delivery and management policies, and products--and by key roles in the health care system--sponsor, plan, provider intermediary organization, and direct services provider. The matrix is a tool for researchers, administrators, clinicians, data collectors, regulators, and other policy makers. It suggests a new set of players to be studied, emphasizes the relationships among the players, and provides a checklist of independent, control, and interactive variables to be included in analyses.

Chromobacterium violaceum infection in Brazil: a case report

We report the second case of infection with Chromobacterium violaceum that occurred in Brazil. A farm worker living in the State of São Paulo presented fever and severe abdominal pain for four days. At hospitalization the patient was in a toxemic state and had a distended and painful abdomen. Chest X-ray and abdominal ultrasound revealed bilateral pneumonia and hypoechoic areas in the liver. The patient developed failure of multiple organs and died a few hours later. Blood culture led to isolation of C. violaceum resistant to ampicillin and cephalosporins and sensitive to chloramphenicol, tetracyclin, aminoglicosydes, and ciprofloxacin. Autopsy revealed pulmonary microabscesses and multiple abscesses in the liver. The major features of this case are generally observed in infections by C. violaceum: rapid clinical course, multiple visceral abscesses, and high mortality. Because of the antimicrobial resistance profile of this Gram-negative bacillus, for appropriate empirical antibiotic therapy it is important to consider chromobacteriosis in the differential diagnosis of severe community infections in Brazil.

[The students' page. Are we making good use of this space?]. / Página do estudante--estamos ocupando este espaço?

The current study aimed to make a survey of the articles written by nursing students that were published through the Students' Pages in the Brazilian Nursing Journal, Nursing Journal from Bahia and Nursing Journal from São Paulo from 1982 to 1995, in order to verify if this space is being used and the themes that have been approached. This investigation evidenced that, from the three studied periodicals, 109 issues were available in the library, 15 presented articles published in the Students' Pages and 21 texts were found. Among these, the most approached themes are related to nursing practice.

Tratamento da mordida cruzada anterior com plano inclinado de acrílico / Anterior cross-bite treated with acrilic inclined plane

Os autores fazem um levantamento sobre a incidência, etiologia, diagnóstico e tratamento da mordida cruzada anterior e, ilustram com a apresentaçäo de caso clínico de um incisivo central em mordida cruzada, tratada com plano inclinado de acrílico

[The quantitative assessment of drug use]. / Avaliação qualitativa no uso de medicamentos.

In a large number of countries where a national health care or a comparable institution is established, precise data on drug utilization are not generally available and often difficult to obtain. This unsatisfactory situation is particularly evident in cases where the preference for drugs in the treatment of certain diseases differ substantially among various countries, since there exists no information about the comparative benefits of the diverse drug regimens. The use of a defined daily dose (DDD) as a unit of measurement makes it possible to compile comparative drug statistics at any time and between regions and countries, independent of changes in prices and currency, as well as differences in drug assortment. The DDD is defined as the assumed average daily doses for adults in the main indication of the drug. It should be emphasized that the DDD is not the recommended dose, but simply a technical unit of measurement.

A flebografia pelvica e a laparoscopia no estudo da congestao pelvica cronica. / Pelvic phlebography and laparoscopy in the study of chronic pelvic congestion

A comparacao dos dados clinicos com os quadros flebograficos e laparoscopicos deixou a impressao de que pode haver alteracao de retorno na pelve, traduzida por um esvaziamento lento do contraste de rede venosa visceral, sem que haja ainda aspecto de varizes pelvicas, enquanto, ao contrario, nao verificamos casos com varizes evidentes a flebografia e/ou laparoscopia com tempos de esvaziamento normais. Ja em relacao a correspondencia entre os dados objetivos fornecidos pelos dois metodos de exame e a clinica de dor pelvica cronica, esta correlacao deixa muito a desejar.Comparando os resultados dos dois metodos, a taxa e de positividade foi de 85% para a laparoscopia e de 70% para a flebografia.E importante salientar que, em cinco casos em que a flebografia foi normal, a laparoscopia mostrou sinais de congestao e/ou varizes nas veias viscerais da pelve. Parece-nos, assim, que a laparoscopia apresenta sobre a flebografia pelvica por via endouterina, em nossa experiencia inicial, claras vantagens como metodo de investigacao para o estudo da circulacao de retorno na pelve

Carriage of Streptococcus agalactiae in women and neonates and distribution of serological types: a study in Brazil.

The prevalence of group B streptococcal carriage was evaluated in nonpregnant women and in mothers and their offsprings. The overall carriage rate of group B streptococci at one site was 18.2%. Streptococci were recovered from one or more of the sites sampled in 25.6% of mothers and 15.4% of newborn infants. The maternal genital carriage rate was 18.6%, and acquisition of the organism from the mother was assessed by serological typing of group B streptococcal isolates in the mother-infant pairs. A cervical carriage rate of 16.3% was seen in nonpregnant women.