Mycobacterium tuberculosis-stimulated whole blood culture to detect host biosignatures for tuberculosis treatment response.

Host markers to monitor the response to tuberculosis (TB) therapy hold some promise. We evaluated the changes in concentration of Mycobacterium tuberculosis (M.tb)-induced soluble biomarkers during early treatment for predicting short- and long-term treatment outcomes. Whole blood samples from 30 cured and 12 relapsed TB patients from diagnosis, week 1, 2, and 4 of treatment were cultured in the presence of live M.tb for seven days and patients followed up for 24 weeks after the end of treatment. 57 markers were measured in unstimulated and antigen-stimulated culture supernatants using Luminex assays. Top performing multi-variable models at diagnosis using unstimulated values predicted outcome at 24 months after treatment completion with a sensitivity of 75.0% (95% CI, 42.8-94.5%) and specificity of 72.4% (95% CI, 52.8-87.3%) in leave-one-out cross validation. Month two treatment responder classification was correctly predicted with a sensitivity of 79.2% (95% CI, 57.8-92.9%) and specificity of 92.3% (95% CI, 64.0-99.8%). This study provides evidence of the early M.tb-specific treatment response in TB patients but shows that the observed unstimulated marker models are not outperformed by stimulated marker models. Performance of unstimulated predictive host marker signatures is promising and requires validation in larger studies.

Distinct serum biosignatures are associated with different tuberculosis treatment outcomes.

Biomarkers for TB treatment response and outcome are needed. This study characterize changes in immune profiles during TB treatment, define biosignatures associated with treatment outcomes, and explore the feasibility of predictive models for relapse. Seventy-two markers were measured by multiplex cytokine array in serum samples from 78 cured, 12 relapsed and 15 failed treatment patients from South Africa before and during therapy for pulmonary TB. Promising biosignatures were evaluated in a second cohort from Uganda/Brazil consisting of 17 relapse and 23 cured patients. Thirty markers changed significantly with different response patterns during TB treatment in cured patients. The serum biosignature distinguished cured from relapse patients and a combination of two clinical (time to positivity in liquid culture and BMI) and four immunological parameters (TNF-ß, sIL-6R, IL-12p40 and IP-10) at diagnosis predicted relapse with a 75% sensitivity (95%CI 0.38-1) and 85% specificity (95%CI 0.75-0.93). This biosignature was validated in an independent Uganda/Brazil cohort correctly classifying relapse patients with 83% (95%CI 0.58-1) sensitivity and 61% (95%CI 0.39-0.83) specificity. A characteristic biosignature with value as predictor of TB relapse was identified. The repeatability and robustness of these biomarkers require further validation in well-characterized cohorts.

An Extended Multilocus Sequence Typing (MLST) Scheme for Rapid Direct Typing of Leptospira from Clinical Samples.

BACKGROUND: Rapid typing of Leptospira is currently impaired by requiring time consuming culture of leptospires. The objective of this study was to develop an assay that provides multilocus sequence typing (MLST) data direct from patient specimens while minimising costs for subsequent sequencing. METHODOLOGY AND FINDINGS: An existing PCR based MLST scheme was modified by designing nested primers including anchors for facilitated subsequent sequencing. The assay was applied to various specimen types from patients diagnosed with leptospirosis between 2014 and 2015 in the United Kingdom (UK) and the Lao Peoples Democratic Republic (Lao PDR). Of 44 clinical samples (23 serum, 6 whole blood, 3 buffy coat, 12 urine) PCR positive for pathogenic Leptospira spp. at least one allele was amplified in 22 samples (50%) and used for phylogenetic inference. Full allelic profiles were obtained from ten specimens, representing all sample types (23%). No nonspecific amplicons were observed in any of the samples. Of twelve PCR positive urine specimens three gave full allelic profiles (25%) and two a partial profile. Phylogenetic analysis allowed for species assignment. The predominant species detected was L. interrogans (10/14 and 7/8 from UK and Lao PDR, respectively). All other species were detected in samples from only one country (Lao PDR: L. borgpetersenii [1/8]; UK: L. kirschneri [1/14], L. santarosai [1/14], L. weilii [2/14]). CONCLUSION: Typing information of pathogenic Leptospira spp. was obtained directly from a variety of clinical samples using a modified MLST assay. This assay negates the need for time-consuming culture of Leptospira prior to typing and will be of use both in surveillance, as single alleles enable species determination, and outbreaks for the rapid identification of clusters.

Differential expression of host biomarkers in saliva and serum samples from individuals with suspected pulmonary tuberculosis.

The diagnosis of tuberculosis remains challenging in individuals with difficulty in providing good quality sputum samples such as children. Host biosignatures of inflammatory markers may be valuable in such cases, especially if they are based on more easily obtainable samples such as saliva. To explore the potential of saliva as an alternative sample in tuberculosis diagnostic/biomarker investigations, we evaluated the levels of 33 host markers in saliva samples from individuals presenting with pulmonary tuberculosis symptoms and compared them to those obtained in serum. Of the 38 individuals included in the study, tuberculosis disease was confirmed in 11 (28.9%) by sputum culture. In both the tuberculosis cases and noncases, the levels of most markers were above the minimum detectable limit in both sample types, but there was no consistent pattern regarding the ratio of markers in serum/saliva. Fractalkine, IL-17, IL-6, IL-9, MIP-1 ß , CRP, VEGF, and IL-5 levels in saliva and IL-6, IL-2, SAP, and SAA levels in serum were significantly higher in tuberculosis patients (P < 0.05). These preliminary data indicate that there are significant differences in the levels of host markers expressed in saliva in comparison to those expressed in serum and that inflammatory markers in both sample types are potential diagnostic candidates for tuberculosis disease.

Avaliação dos contextos de atuação, atribuições e mercado profissional: opinião da população sobre a Psicologia e o Psicólogo / Evaluation of the contexts of performance, assignments, and professional market: the population’s opinion on Psychologist and Psychology

Identificar como as pessoas percebem uma prática profissional possibilita o reconhecimento de seus aspectos positivos e debilidades, seja no processo de formação acadêmica, ou no próprio exercício da profissão. É nesse contexto que este estudo visa verificar a opinião da população sobre o profissional de Psicologia, principalmente quanto ao contexto de atuação, atribuições e mercado profissional. Para tanto, realizou-se um estudo descritivo, que analisou 102 respostas hospedadas em um sítio eletrônico na internet. Os resultados sugerem o reconhecimento de quatro contextos de atuação (clínica, organizacional, escolar e hospitalar), no entanto, com atribuições esperadas da prática clínica, por meio das categorias: facilita o autoconhecimento, cura, aumento da qualidade de vida, escuta e aconselhamento psicológico. Opiniões opostas quanto ao mercado de trabalho foram observadas: alguns percebem a Psicologia como um campo flexível e em crescimento, enquanto outros destacam a saturação do mercado e desvalorização do profissional.

Identifying how people perceive a professional practice enables the recognition of their strengths and weaknesses, whether in the academic learning process, or in the exercise of the profession. In this context, this study aims to verify the population’s opinion on the Psychology professional, mainly in the context of performance, assignments, and professional market. For this purpose, we conducted a descriptive study, which analyzed 102 responses hosted on an electronic site on the Internet. The results suggest mainly the recognition of four contexts of activity (clinic, organization, school, and hospital), however, with assignments expected in the clinical practice, expressed by the categories: facilitating the process of self-knowledge, healing, increased quality of life, listening and counseling. Opposing views on the labor market have been observed in this study: some perceive psychology as a flexible and growing field, while others emphasize the market saturation and profession devaluation.

Development of a diagnostic gene expression assay for tuberculosis and its use under field conditions in African buffaloes (Syncerus caffer).

The development of diagnostic tests for tuberculosis (TB) in exotic species is constrained by host biology and the limited availability of suitable assay reagents. As such, we evaluated a gene expression assay (GEA) which is easily modified for novel species and allows for initial sample processing under field conditions. African buffaloes (Syncerus caffer) were categorized using the single comparative intradermal tuberculin test, and blood from test-positive and test-negative animals was incubated for 20 h in "Nil" tubes (containing saline) and "TB Antigen" tubes (containing Mycobacterium tuberculosis complex (MTC)-specific antigens) of a commercial human TB test, the QuantiFERON(®)-TB Gold (In-Tube) (QFT) assay. Blood samples were then stabilized in RNAlater(®) and transported to the laboratory for RNA extraction. A Custom TaqMan GEA was used to calculate the relative abundance of interferon-gamma (IFN-γ) mRNA in the TB Antigen tube compared to that in the Nil tube as a marker of immune activation in response to MTC antigen recognition. The GEA results from the two buffalo groups were compared and a cutoff value of 2.85 was calculated to differentiate between animals from these groups with a sensitivity of 80% (95% C.I.: 56-94%) and a specificity of 95% (95% C.I.: 75-100%). Further optimization of this assay could provide a highly useful tool for the diagnosis of MTC infection in exotic species.

Risk factors associated with positive QuantiFERON-TB Gold In-Tube and tuberculin skin tests results in Zambia and South Africa.

INTRODUCTION: The utility of T-cell based interferon-gamma release assays for the diagnosis of latent tuberculosis infection remains unclear in settings with a high burden of tuberculosis. OBJECTIVES: To determine risk factors associated with positive QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST) results and the level of agreement between the tests; to explore the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST. METHODS: Adult household contacts of tuberculosis patients were invited to participate in a cross-sectional study across 24 communities in Zambia and South Africa. HIV, QFT-GIT and TST tests were done. A questionnaire was used to assess risk factors. RESULTS: A total of 2,220 contacts were seen. 1,803 individuals had interpretable results for both tests, 1,147 (63.6%) were QFT-GIT positive while 725 (40.2%) were TST positive. Agreement between the tests was low (kappa = 0.24). QFT-GIT and TST results were associated with increasing age (adjusted OR [aOR] for each 10 year increase for QFT-GIT 1.15; 95% CI: 1.06-1.25, and for TST aOR: 1.10; 95% CI 1.01-1.20). HIV positivity was less common among those with positive results on QFT-GIT (aOR: 0.51; 95% CI: 0.39-0.67) and TST (aOR: 0.61; 95% CI: 0.46-0.82). Smear positivity of the index case was associated with QFT-GIT (aOR: 1.25; 95% CI: 0.90-1.74) and TST (aOR: 1.39; 95% CI: 0.98-1.98) results. We found little evidence in our data to support our hypotheses. CONCLUSION: QFT-GIT may not be more sensitive than the TST to detect risk factors associated with tuberculous infection. We found little evidence to support the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST.

Distribuição da procedência de pacientes operados de câncer de pele não-melanoma no Hospital Aristides Maltez e sua relação com mapeamento populacional no estado da Bahia / Distribution of the precedence from non-melanoma skin cancer operated patients in Hospital Aristides Maltez during 2002 and their relationship with populational studies in Bahia

O câncer de pele é o mais freqüente entre os humanos sendo o Melanoma Maligno (MM) um dos mais letais, apresentando maiores índices de mortalidade nos países menos desenvolvidos onde o Câncer de Pele Não-Melanoma (CPNM) costuma ser um grave problema de saúde pública. No Brasil o difícil acesso ao tratamento do câncer de pele entre as populações pobres permite óbito na maioria dos casos de MM e um número importante de mutilações por CPNM. Com uma predominância bem estabelecida entre as populações brancas em todo o mundo assim como uma marcante relação com foto-exposição solar, o Câncer de Pele necessita de maiores estudos epidemiológicos em nossa região. O objetivo deste trabalho foi distribuir a procedência dos pacientes operados de CPNM no serviço de dermatologia do hospital referência para câncer na Bahia pelas áreas anteriormente mapeadas como de população branca, por Azevedo e cols. para verificar se a maioria deles realmente provinha destas áreas. Como resultado foram obtidos 88 protocolos dos pacientes operados dos quais 54 vieram da área de brancos e 34 da área de não-brancos, um resultado estatisticamente significante (p<0,05). Conclui-se que esse mapeamento anterior correspondia à procedência da maioria dos pacientes o que pode servir como subsídio para futuras ações preventivas e curativas que possam ser adotadas para a prevenção do câncer de pele na Bahia.

Psoríase / Psoriasis

Os autores descrevem dois casos clínicos de psoríasis, um dos quais em que as lesões são de localização exclusivamente bucal. Fazem revisão da literatura médica e odontológica, demonstrando o pouco conhecimento que se tem com relação à localização bucal desta enfermidade