Endocardite por Coxiella burnetii (febre Q): doença rara ou pouco diagnosticada? Relato de caso

A febre Q é uma zoonose de distribuição mundial causada por Coxiella burnetii, sendo raros os registros da doença no Brasil. Estudos soroepidemiológicos mostraram uma freqüência relativamente elevada de anticorpos contra Coxiella burnetii em populações com exposição ocupacional. Em humanos, pode se manifestar clinicamente como doença aguda ou crônica, sendo que a endocardite é a forma crônica mais freqüente da febre Q e de maior morbi-mortalidade. Relatamos um caso grave de endocardite por Coxiella burnetii adquirida no Brasil com desfecho fatal, apesar de antibioticoterapia adequada e tratamento cirúrgico valvar.

Molecular identification of the agent of Q fever – Coxiella burnetii – in domestic animals in State of Rio de Janeiro, Brazil

Introduction Over the last recent years, the number of Q fever cases have has increased throughout the world. An epidemiological investigation was performed in the area in which the first molecular documentation of Q fever in Brazil was previously reported. Methods Indirect immunofluorescence assay (IFA) and PCR of Coxiella burnetii targeting the htpAB gene were performed in samples from 14 dogs (blood); 1 cat (blood); 10 goats (blood, milk, vaginal swab and anal swab); 3 sheep (blood); and 2 horses (blood). Results Two dogs, two sheep and five goats were seroreactive. DNA was amplified from 6 milk and 2 blood samples from goats and from dogs, respectively. The sequence of the amplicons exhibited 99% sequence similarity with the homologous sequence of the htpAB gene of C. burnetii RSA 331 (GenBank - CP000890). Conclusions The results confirm C. burnetii infection in animals in Rio de Janeiro and reinforce the need for the surveillance of Q fever in Brazil.

G-quadruplex ligands for cancer therapy

DNA may fold into a diversity of structures and topologies such as duplexes and triplexes. Some specific guanine-rich DNA sequences may even fold into a higher order structures denominated guanine G-quadruplexes (G4). These G-quadruplex forming sequences have shown biological interest since were found in telomeres and in promoter region of oncogenes. Thus, these G4 forming sequences have been explored as therapeutic targets for cancer therapy, since G4 formation was demonstrated to inhibit RNA-polymerase and telomerase activity. However, the G4 structures are transient and are only formed under specific conditions. Hence the main objective of this work is to develop new G4-specific ligands which may potentially find applications in the therapeutic area. Several potential G4-binding ligands were synthesized and characterized. The synthesis of these compounds consisted on a procedure based on van Leusen chemistry and a cross-coupling reaction through C-H activation, affording phenanthroline compounds (Phen-1, 50%; Phen-2, 20%), phenyl (Iso-1, 61%; Iso-2, 21%; Ter-1, 85%; Ter-2, 35%), and quinolyl (Quin-1, 85%; Quin-2, 45%) compounds. Screening assays for selecting the potential G4 compounds were performed by FRET-melting, G4-FID, CD-melting and DSF. Qualitative biophysical studies were performed by fluorescence and CD spectroscopy. Two high-specific G-quadruplex ligands, Phen-1 and Phen-2, were found to effectively bind telomeric and c-myc G4 structures. Phen-1 was found to stabilize parallel telomeric 22AG and c-myc sequence by 4.1 and 4.3 ˚C, respectively. Phen-2 also displayed high affinity towards 22AG (

Nickel(II) complexes of bidentate N-N′ ligands containing mixed pyrazole, pyrimidine and pyridine aromatic rings as catalysts for ethylene polymerisation

This work describes the synthesis and characterisation of Ni(II) complexes of the following neutral bidentate nitrogen ligands containing pyrazole (pz), pyrimidine (pm) and pyridine (py) aromatic rings: 2-pyrazol-1-yl-pyrimidine (pzpm), 2-(4-methyl-pyrazol-1-yl)-pyrimidine (4-Mepzpm), 2-(4-bromo-pyrazol-1-yl)-pyrimidine (4-Brpzpm), 2-(3,5-dimethyl-pyrazol-1-yl)-pyrimidine (pz*pm), 2-pyrazol-1-yl-pyridine (pzpy) and bis(3,5-dimethylpyrazol-1-yl)phenylmethane (bpz*mph). The complexes [NiBr2(pzpm)] (1), [NiBr2(4-Mepzpm)] (2), [NiBr2(4-Brpzpm)] (3), [NiBr2(pz*pm)] (4), [NiBr2(pzpy)] (5) and [NiBr2(bpz*mph)] (6) were tested as catalysts for ethylene polymerisation, in the presence of the cocatalysts methylaluminoxane (MAO) or diethylaluminium chloride (AlEt2Cl), the catalyst systems 1-3/MAO showing moderate to high activities up to the temperature of 20 °C only in the presence of MAO, whereas 4-6/MAO revealed to be inactive. Other related Pd(II) complexes, already reported in previous works, such as [PdClMe(pzpm)], [PdClMe(pz*pm)], [PdClMe(pzpy)] and [PdClMe(bpz*mph)], also showed to be inactive in the polymerisation of ethylene, when activated by MAO or AlEt2Cl. Selected samples of polyethylene products were characterised by GPC/SEC, 1H and 13C NMR and DSC, showing to be low molecular weight polymers with Mn values ranging from ca. 550 to 1500 g mol−1 and unusually low dispersities of 1.2–1.7, with total branching degrees generally varying between 2 and 12%, melting temperatures from 40 to 120 °C and crystallinities from 40 to 70%.

Validação para o português do Maugerl CaRdiac preventiOn-Questionnaire (MICRO-Q)

FUNDAMENTO: O Maugerl CaRdiac preventiOn-Questionnaire (MICRO-Q) é um instrumento específico, validado e utilizado para avaliar o conhecimento do paciente coronariano sobre aspectos relacionados à prevenção secundária da doença arterial coronariana (DAC). OBJETIVO: Traduzir, adaptar e validar o MICRO-Q para a língua portuguesa do Brasil. MÉTODOS: Duas traduções iniciais independentes foram realizadas para o português. Após sua comparação foi feita a tradução reversa, que foi revisada por um comitê e gerou a versão final, testada em um estudo-piloto. O instrumento foi aplicado em 212 pacientes coronarianos, com idade média de 60 a 72 anos (desvio padrão = 9,4; mín = 35; máx = 86), participantes de programas de reabilitação cardíaca. A consistência interna foi verificada por meio do coeficiente Alpha de Cronbach, a correlação através do Spearman Rho e a validade de construto foi verificada por análise fatorial exploratória. As médias foram analisadas comparando as escalas das questões corretas em função de variáveis, como idade, sexo, comorbidades associadas, grau de escolaridade, renda familiar, entre outros. RESULTADOS: A versão brasileira do MICRO-Q possui 25 questões. Essa versão, quanto à confiabilidade, apresentou Alpha de Cronbach de 0,64 e Spearman Rho das respostas corretas de 0,65. A análise fatorial revelou a existência de 6 fatores, relacionados aos domínios de conhecimento do questionário. A análise das características da população, em função das escalas das questões corretas, apresentou diferenças significativas apenas em função da renda familiar mensal e grau de escolaridade. CONCLUSÃO: A versão brasileira do MICRO-Q aprovada apresenta validade e confiabilidade adequadas para sua utilização em futuras pesquisas.

Construção e validação do "CADE-Q" para educação de pacientes em programas de reabilitação cardíaca

FUNDAMENTO: O conhecimento sobre a doença arterial coronariana pode ser considerado o primeiro passo para reduzir o risco de complicações cardíacas. OBJETIVOS: Construir e validar um instrumento capaz de avaliar e descrever o conhecimento do paciente coronariano em programas de reabilitação cardíaca, com a finalidade de educação. MÉTODOS: Para construção, foi realizada análise de artigos e estudo de campo para a apresentação de itens a uma equipe multidisciplinar associada à reabilitação cardíaca. Após análise, foi gerada a versão testada em um estudo-piloto. O instrumento, nomeado CADE-Q (Questionário para Educação do Paciente Coronariano), foi aplicado em 155 pacientes com idade de 61 ± 9 anos (mín = 36 ; máx = 86), participantes de programas de reabilitação cardíaca. Dos 155 pacientes, 114 eram homens. A consistência interna foi verificada pelo coeficiente Alpha de Cronbach. A reprodutibilidade foi testada através do coeficiente de correlação intraclasse (CCIC) e a validade de construto por análise fatorial exploratória. Foi realizada análise comparando os escores totais em função de características da população e entre os grupos de reabilitação (privado e público). RESULTADOS: A versão final possui 19 questões com 4 alternativas, com 4 quadrantes de conhecimento. O Alpha de Cronbach foi de 0,68 e CCIC foi de 0,783. A análise fatorial revelou 6 fatores, abrangendo três áreas de conhecimento, o que demonstra a multifatoriedade do instrumento. A análise das características da população em função do escore total apresentou diferenças significativas em função das variáveis do nível socioeconômico (tipo de reabilitação, renda familiar e escolaridade). CONCLUSÃO: O instrumento CADE-Q apresenta validade e confiabilidade adequadas para sua utilização na população brasileira em futuras pesquisas.

Le Q-sort, un outil pour la recherche en soins le cas des représentations chez les infirmiers en psychiatrie de l'âge avancé [Q-sort, a useful research method in care in cases of psychiatric nursing of the aged]

Q-sort is a research method which allows defining profiles of attitudes toward a set of statements, ordered in relation to each other. Pertaining to the Q Methodology, the qualitative analysis of the Q-sorts is based on quantitative techniques. This method is of particular interest for research in health professions, a field in which attitudes of patients and professionals are very important. The method is presented in this article, along with an example of application in nursing in old age psychiatry.

Characterisation of heteromers and oligomers in the TNF family of ligands and receptors

TNF family ligands and receptors fulfill a number of functions, mainly in the immune system. For example, the ligands BAFF and APRIL control growth and survival of mature Β cells at various stages of differentiation. TNF family ligands usually form homotrimers, but heteromers have also been described for lymphotoxin α1β2 and for BAFF and APRIL. Interestingly, twenty BAFF homotrimers can assemble into virus-like particles coined BAFF 60-mer, which are superior to BAFF 3-mer regarding their ability to signal in primary Β cells. A screen was performed in 293T cells, by co-transfecting differently tagged ligands, to identify six novel heteromers. The specificity of these novel heteromers, however, did not correspond to that of orphan receptors in the TNFR family. Little is known about heteromers of BAFF and APRIL, in particular their receptor-binding specificity and their ability to signal. A method to produce and purify heteromers of defined stoechiometry was developed, and the resulting reagents were used to demonstrate that BAFF2APRIL, like BAFF, binds to all BAFF receptors - namely BAFFR, TACI and Β CM A -, while APRIL2BAFF and APRIL only binds to TACI and BCMA. Heteromers could signal via their cognate receptors, sometimes as potently and sometimes less potently than homomers, depending on the receptors. A promising system to measure the activity of single-chain homo- and heteromers in vivo was set up: it measures mature Β cell rescue upon administration of single-chain ligands into BAFF-ko mice. To tackle the question of the physiological importance of BAFF 60-mer, a point mutation that prevents assembly of mouse BAFF into 60-mer while retaining its ability to form trimers was identified. This mutation (E247K) was introduced by homologous recombination into mouse embryonic stem cells that are now being used to generate knock-in mice. Results obtained in this work will help to better understand the role of various BAFF and APRIL forms that are elevated in a several autoimmune diseases. - Les ligands et récepteurs de la famille du TNF joue un rôle prédominant dans le système immunitaire. Par exemple, les ligands BAFF et APRIL contrôlent la croissance et la survie des cellules Β matures à différents stades de différenciation. Ces ligands existent souvent sous forme d'homotrimères (3-mer), bien que des héteromères aient été décrits pour la lymphotoxine α1β2 et pour BAFF et APRIL. Dans le cas de BAFF, vingt trimères peuvent, telle une particule virale, s'assembler en 60-mer qui surpasse le 3-mer pour signaler dans des cellules Β primaires. Un crible effectué dans des cellules 293T, par co-transfection de ligands différemment marqués, a permis d'identifier six nouveaux heteromères dont la spécificité n'a, hélas, pas correspondu à celle d'un récepteur orphelin de la famille du TNFR. Les connaissances sur la spécificité de liaison aux récepteurs et la capacité à signaler des heteromères de BAFF et d'APRIL sont fragmentaires. Une méthode pour produire et purifier des heteromères "simple chaîne" de stoechiométrie déterminée a été mise au point, et les réactifs ainsi obtenus utilisés pour démontrer que BAFF2APRIL, comme BAFF, lie tous les récepteurs de BAFF - c'est-à-dire BAFFR, TACI et BCMA -, alors qu'APRIL2BAFF et APRIL ne lient que TACI et BCMA. Les héteromères peuvent transmettre des signaux, parfois aussi bien et parfois plus faiblement que les homomères, selon les récepteurs. Un système prometteur pour mesurer l'activité des ligands simple chaîne in vivo a été mis au point. Il mesure la réapparition de cellules Β matures dans des souris déficientes pour BAFF après administration des ligands. Pour s'attaquer à la question de l'importance physiologique du 60-mer de BAFF, ime mutation empêchant l'assemblage en 60-mer sans affecter la capacité à former des trimères a été identifiée. Cette mutation (E247K) a été introduite par recombinaison homologue dans des cellules souches embryonnaires de souris qui sont utilisées pour obtenir des souris déficientes en BAFF 60-mer. Les résultats de ces travaux contribueront à mieux cerner le rôle des différentes formes de BAFF et d'APRIL produites en excès dans plusieurs maladies auto-immunes.

Detecting and measuring deprivation in primary care: development, reliability and validity of a self-reported questionnaire: the DiPCare-Q.

OBJECTIVES: Advances in biopsychosocial science have underlined the importance of taking social history and life course perspective into consideration in primary care. For both clinical and research purposes, this study aims to develop and validate a standardised instrument measuring both material and social deprivation at an individual level. METHODS: We identified relevant potential questions regarding deprivation using a systematic review, structured interviews, focus group interviews and a think-aloud approach. Item response theory analysis was then used to reduce the length of the 38-item questionnaire and derive the deprivation in primary care questionnaire (DiPCare-Q) index using data obtained from a random sample of 200 patients during their planned visits to an ambulatory general internal medicine clinic. Patients completed the questionnaire a second time over the phone 3 days later to enable us to assess reliability. Content validity of the DiPCare-Q was then assessed by 17 general practitioners. Psychometric properties and validity of the final instrument were investigated in a second set of patients. The DiPCare-Q was administered to a random sample of 1898 patients attending one of 47 different private primary care practices in western Switzerland along with questions on subjective social status, education, source of income, welfare status and subjective poverty. RESULTS: Deprivation was defined in three distinct dimensions: material (eight items), social (five items) and health deprivation (three items). Item consistency was high in both the derivation (Kuder-Richardson Formula 20 (KR20) =0.827) and the validation set (KR20 =0.778). The DiPCare-Q index was reliable (interclass correlation coefficients=0.847) and was correlated to subjective social status (r(s)=-0.539). CONCLUSION: The DiPCare-Q is a rapid, reliable and validated instrument that may prove useful for measuring both material and social deprivation in primary care.

Parallel spinors on pseudo-riemannian spin(q) manifolds

We study simply-connected irreducible non-locally symmetric pseudo-Riemannian Spin(q) manifolds admitting parallel quaternionic spinors.

Altered ligands reveal limited plasticity in the T cell response to a pathogenic epitope.

Experimental leishmaniasis offers a well characterized model of T helper type 1 cell (Th1)-mediated control of infection by an intracellular organism. Susceptible BALB/c mice aberrantly develop Th2 cells in response to infection and are unable to control parasite dissemination. The early CD4(+) T cell response in these mice is oligoclonal and reflects the expansion of Vbeta4/ Valpha8-bearing T cells in response to a single epitope from the parasite Leishmania homologue of mammalian RACK1 (LACK) antigen. Interleukin 4 (IL-4) generated by these cells is believed to direct the subsequent Th2 response. We used T cells from T cell receptor-transgenic mice expressing such a Vbeta4/Valpha8 receptor to characterize altered peptide ligands with similar affinity for I-Ad. Such altered ligands failed to activate IL-4 production from transgenic LACK-specific T cells or following injection into BALB/c mice. Pretreatment of susceptible mice with altered peptide ligands substantially altered the course of subsequent infection. The ability to confer a healer phenotype on otherwise susceptible mice using altered peptides that differed by a single amino acid suggests limited diversity in the endogenous T cell repertoire recognizing this antigen.