Preclinical Target Validation Using Patient-derived Cells.

The Structural Genomics Consortium (SGC) and its clinical, industry and disease-foundation partners are launching open-source preclinical translational medicine studies.

Immediate implants placed into infected sockets: a case report with 3-year follow-up

The esthetics and functional integrity of the periodontal tissue may be compromised by dental loss. Immediate implants became a viable option to maintain the periodontal architecture because of their anatomic compatibility with the dental socket and the possibility of eliminating local contamination. This article describes the procedure of immediate implant placement in the anterior maxilla replacing teeth with chronic periapical lesions, which were condemned due to endodontic lesions persisting after failed endodontic treatment and endodontic surgery, and discusses the relationship between the procedure and periapical lesions. Surgical removal of hopeless teeth 11, 12 and 21 was performed conservatively in such a way to preserve the anatomy and gingival esthetics. A second surgical access was gained at the apical level, allowing the debridement of the surgical chamber for elimination of the periapical lesion, visual orientation for setting of the implants and filling of the surgical chamber with xenogenous bovine bone graft. After this procedure, the bone chamber was covered with an absorbent membrane and the healing screws were positioned on the implants. Later, a provisional partial removable denture was installed and the implants were inserted after 6 months. After 3 years of rehabilitation, the implants present satisfactory functional and esthetic conditions, suggesting that immediate implant placement combined with guided bone regeneration may be indicated for replacing teeth lost due to chronic periapical lesions with endodontic failure history in the anterior maxilla.

The Effects of Commercially Available Preservative-Free FDA-Approved Triamcinolone (Triesence (R)) on Retinal Cells in Culture

Purpose: To evaluate the effects of Triesence (R) (TRI), a new preservative-free triamcinolone approved by the U. S. Food and Drug Administration (FDA) for intraocular use, on human retina pigment epithelial (ARPE-19) and rat neurosensory (R28) cells in culture. Methods: ARPE-19 and R28 cell cultures were treated 24 h with 1,000, 500, 200, or 100 mu g/mL of crystalline (cTRI) or 1,000, 500, or 200 mu g/mL of solubilized (sTRI). TRI was solubilized by centrifuging the drug, discarding the supernatant containing the vehicle and then resuspending the drug pellet in an equivalent amount of Dimethyl sulfoxide to achieve the same concentration as the commercial preparation. Percentage of cell viability (CV) was evaluated by a trypan blue dye-exclusion assay. The mitochondrial membrane potential (Delta Psi m) was analyzed with the JC-1 assay. The caspase-3/7 activity was measured by a fluorochrome assay. Results: In the ARPE-19 cultures, the cTRI caused a decrease in CV at 1,000 mg/mL (13.03 +/- 6.51; P < 0.001), 500 mu g/mL (28.87 +/- 9.3; P < 0.001), 200 mu g/mL (54.93 +/- 5.61; P < 0.001), and 100 mu g/mL (82.53 +/- 0.65; P < 0.005) compared with the untreated controls (96.98 +/- 0.16). In R28 cultures, the cTRI treatment also reduced CV values significantly (P < 0.001) for the 1,000 mu g/mL (22.73 +/- 2.44), 500 mu g/mL (34.63 +/- 1.91), 200 mu g/mL (58.70 +/- 1.39), and 100 mu g/m (75.33 +/- 2.47) compared with the untreated controls (86.08 +/- 3.54). Once the TRI was solubilized (sTRI), the CV and Delta Psi m remained similar to the untreated controls for both ARPE-19 and R28 cells. The sTRI treatment with 1,000, 500, and 200 mu g/mL increased in caspase-3/7 activity in ARPE-19 cells (P < 0.01) and in R28 cells (P < 0.05) compared with dimethyl sulfoxide equivalent controls. Conclusion: The crystalline form of TRI (cTRI) can cause a significant decrease in CV to cultured retinal cells. Once the TRI is solubilized (sTRI), at the same concentrations, the cells remain viable with no decrease in CV or Delta Psi m. The sTRI can, however, increase caspase-3/7 activity, thus suggesting some degree of apoptosis.

Nitrogen availability patterns in white-sand vegetations of Central Brazilian Amazon

Addressing spatial variability in nitrogen (N) availability in the Central Brazilian Amazon, we hypothesized that N availability varies among white-sand vegetation types (campina and campinarana) and lowland tropical forests (dense terra-firme forests) in the Central Brazilian Amazon, under the same climate conditions. Accordingly, we measured soil and foliar N concentration and N isotope ratios (delta(15)N) throughout the campina-campinarana transect and compared to published dense terra-firme forest results. There were no differences between white-sand vegetation types in regard to soil N concentration, C:N ratio and delta(15)N across the transect. Both white-sand vegetation types showed very low foliar N concentrations and elevated foliar C:N ratios, and no significant difference between site types was observed. Foliar delta(15)N was depleted, varying from -9.6 to 1.6aEuro degrees in the white-sand vegetations. The legume Aldina heterophylla had the highest average delta(15)N values (-1.5aEuro degrees) as well as the highest foliar N concentration (2.1%) while the non-legume species had more depleted delta(15)N values and the average foliar N concentrations varied from 0.9 to 1.5% among them. Despite the high variation in foliar delta(15)N among plants, a significant and gradual (15)N-enrichment in foliar isotopic signatures throughout the campina-campinarana transect was observed. Individual plants growing in the campinarana were significantly enriched in (15)N compared to those in campina. In the white-sand N-limited ecosystems, the differentiation of N use seems to be a major cause of variations observed in foliar delta(15)N values throughout the campina-campinarana transect.

Comparison of Quantitative T-Wave Alternans Profiles of Healthy Subjects and ICD Patients

Background: Current relevance of T-wave alternans is based on its association with electrical disorder and elevated cardiac risk. Quantitative reports would improve understanding on TWA augmentation mechanisms during mental stress or prior to tachyarrhythmias. However, little information is available about quantitative TWA values in clinical populations. This study aims to create and compare TWA profiles of healthy subjects and ICD patients, evaluated on treadmill stress protocols. Methods: Apparently healthy subjects, not in use of any medication were recruited. All eligible ICD patients were capable of performing an attenuated stress test. TWA analysis was performed during a 15-lead treadmill test. The derived comparative profile consisted of TWA amplitude and its associated heart rate, at rest (baseline) and at peak TWA value. Chi-square or Mann-Whitney tests were used with p values <= 0.05. Discriminatory performance was evaluated by a binary logistic regression model. Results: 31 healthy subjects (8F, 23M) and 32 ICD patients (10F, 22M) were different on baseline TWA (1 +/- 2 mu V; 8 +/- 9 mu V; p < 0.001) and peak TWA values (26 +/- 13 mu V; 37 +/- 20 mu V; p = 0,009) as well as on baseline TWA heart rate (79 +/- 10 bpm; 67 +/- 15 bpm; p < 0.001) and peak TWA heart rate (118 +/- 8 bpm; 90 +/- 17 bpm; p < 0.001). The logistic model yielded sensitivity and specificity values of 88.9% and 92.9%, respectively. Conclusions: Healthy subjects and ICD patients have distinct TWA profiles. The new TWA profile representation (in amplitude-heart rate pairs) may help comparison among different research protocols. Ann Noninvasive Electrocardiol 2009;14(2):108-118.

Soroepidemiologia da tripanosomíase americana na região do litoral sul, São Paulo

OBJETIVO: Analisar dados de reações sorológicas realizadas em dois períodos, entre fins da década de 1960 e o ano de 1983, quando a sorologia passou a complementar a informação sobre triatomíneos vetores do Estado de São Paulo e, de 1984 até 1999, caracterizando o panorama atual da endemia nessa região. MÉTODOS: Foram realizadas análises soroepidemiológicas de reações, obtidas em inquéritos escolares (fins da década de 1960 e entre 1973 e 1983), em inquéritos populacionais em Cananéia, Iguape e Peruíbe (entre 1980 e 1982) e em moradores de unidades domiciliares. Os resultados da análise foram associados a informações obtidas sobre os vetores encontrados. RESULTADOS: Manteve-se a sororreatividade entre escolares em patamares baixos, porém constantes, ao longo dos anos 1973 a 1982, tornando-se nulos em 1983. A curva de freqüência de distribuição de títulos demonstrou um padrão típico de área negativa no município de Cananéia e de baixa endemicidade nos demais. A investigação de casos revelou predominância de importados e, quando autóctones, sugestivos de transmissão oral. Foram observadas 1.261 unidades domiciliares com relato de presença de triatomíneos vetores (principais espécies: Panstrongylus megistus e Triatoma tibiamaculata), com um total de 5.338 amostras de sangue colhidas e 40 sororreagentes (0,75%). Exemplares adultos predominaram no intradomicílio e cerca da metade deles sem ingesta de sangue humano. Não foi observada diferença entre resultados de sorologia em moradores de casas com triatomíneos infectados e não infectados por Trypanosoma cruzi. CONCLUSÕES: Os resultados mostram ser necessário desenvolver um trabalho integrado entre instituições, que permita o isolamento e estudos de cepas e de isolados de tripanosomatídeos presentes em vetores, reservatórios (domésticos ou não) e humanos, com o objetivo de observar a interação dos pontos de vista evolutivo, de patogenia e de ecologia, de eventuais diferentes linhagens.

Reliability of a questionnaire on substance use among adolescent students, Brazil

OBJECTIVE: To analyze reliability of a self-applied questionnaire on substance use and misuse among adolescent students. METHODS: Two cross-sectional studies were carried out for the instrument test-retest. The sample comprised male and female students aged 1119 years from public and private schools (elementary, middle, and high school students) in the city of Salvador, Northeastern Brazil, in 2006. A total of 591 questionnaires were applied in the test and 467 in the retest. Descriptive statistics, the Kappa index, Cronbach's alpha and intraclass correlation were estimated. RESULTS: The prevalence of substance use/misuse was similar in both test and retest. Sociodemographic variables showed a "moderate" to "almost perfect" agreement for the Kappa index, and a "satisfactory" (>0.75) consistency for Cronbach's alpha and intraclass correlation. The age which psychoactive substances (tobacco, alcohol, and cannabis) were first used and chronological age were similar in both studies. Test-retest reliability was found to be a good indicator of students' age of initiation and their patterns of substance use. CONCLUSIONS: The questionnaire reliability was found to be satisfactory in the population studied.

Eficiência do diagnóstico coproscópico de Schistosoma mansoni em fezes prensadas

A eficácia do controle da esquistossomose depende em grande parte da sensibilidade da coproscopia. Passamos a utilizar, além da técnica de Kato-Katz, a de prensagem de fezes entre lâmina e lamínula de polipropileno, segundo Ferreira. De 1.282 amostras fecais colhidas entre 1998 e 2000 no Bairro da Palha, Município de Bananal, São Paulo, Brasil, 105 (8,2%) resultaram positivas. A primeira técnica revelou 90 (7%) e a segunda, 88 (6,9%) amostras positivas. Os resultados concordaram, segundo a estatística kappa. Valores baixos de percentagens de positivos e de opg (ovos por grama) de fezes, em Bananal, demandaram aumento do volume de material a examinar. Além de permitir a observação da viabilidade dos ovos de Schistosoma mansoni, a segunda técnica dispensa o uso de glicerina, de placa medidora e de tamisação; esta última, responsável por ulterior perda de precisão nas determinações de opg.

Efeitos das mudanças do uso da terra na biogeoquímica dos corpos d'água da bacia do rio Ji-Paraná, Rondônia

Este trabalho discute os efeitos das mudanças do uso do solo na biogequímica dos rios da bacia de drenagem do rio Ji-Paraná (Rondônia). Nesta região, a distribuição espacial do desmatamento e das propriedades do solo resultam em sinais diferentes, possibilitando a divisão dos sistemas fluviais em três grupos: rios com águas pobres em íons e baixo impacto; rios com conteúdo iônico intermediário e impacto médio e rios com elevados conteúdo iônico e impacto antropogênico. As características biogeoquímicas dos rios têm relação significativa com a área de pasto, melhor parâmetro para prever a condutividade elétrica (r² = 0,87) e as concentrações de sódio (r² = 0,75), cloreto (r² = 0,69), potássio (r² = 0,63), fosfato (r² = 0.78), nitrogênio inorgânico (r² = 0.52), carbono inorgânico (r² = 0.81) e carbono orgânico (rain ² = 0.51) dissolvidos. Cálcio e magnésio tiveram sua variância explicada pelas características do solo e pastagem. Nossos resultados indicam que as mudanças observadas na micro-escala constituem "sinais biogeoquímicos" gerados pelo processamento do material nas margens dos rios. A medida em que os rios evoluem para ordens superiores, os sinais persistentes nos canais fluviais estão mais associdados às características da bacia de drenagem (solos e uso da terra). Apesar dos efeitos das mudanças observadas no uso do solo não serem ainda detectáveis na macro-escala (bacia amazônica), a disrupção da estrutura e funcionamento dos ecossistemas é detectável nas micro e meso escalas, com alterações significativas na ciclagem de nutrientes nos ecossistemas fluviais.

Die Tier- und Pflanzenwelt des Süsswassers : Einführung in das Studium derselben.

2

Die Tier- und Pflanzenwelt des Süsswassers : Einführung in das Studium derselben.

1

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Multivariate contemporaneous-threshold autoregressive models

This paper proposes a contemporaneous-threshold multivariate smooth transition autoregressive (C-MSTAR) model in which the regime weights depend on the ex ante probabilities that latent regime-specific variables exceed certain threshold values. A key feature of the model is that the transition function depends on all the parameters of the model as well as on the data. Since the mixing weights are also a function of the regime-specific innovation covariance matrix, the model can account for contemporaneous regime-specific co-movements of the variables. The stability and distributional properties of the proposed model are discussed, as well as issues of estimation, testing and forecasting. The practical usefulness of the C-MSTAR model is illustrated by examining the relationship between US stock prices and interest rates.

State-dependent threshold STAR models

In this paper we consider extensions of smooth transition autoregressive (STAR) models to situations where the threshold is a time-varying function of variables that affect the separation of regimes of the time series under consideration. Our specification is motivated by the observation that unusually high/low values for an economic variable may sometimes be best thought of in relative terms. State-dependent logistic STAR and contemporaneous-threshold STAR models are introduced and discussed. These models are also used to investigate the dynamics of U.S. short-term interest rates, where the threshold is allowed to be a function of past output growth and inflation.

Schistosomiasis mansoni in Bananal (State of São Paulo, Brazil): IV. Study on the public awareness of its risks in the Palha District

A rather high prevalence of mansoni schistosomiasis has been observed in some localities of Bananal, State of São Paulo, during the past decade. The highest prevalence of schistosomiasis was found in the Palha District; it was thus considered adequate for an evaluation of public awareness of the risks involved in acquiring schistosomiasis, a likely outcome of certain behavior patterns. We interviewed 542 district-dwellers. The 5-to-39 age-group constituted 65.5% of the whole sample. Concerning the infection, 69.2% had hearsay information; 46.1% know the infection; 69.6% know how it is acquired; 31.5% know about the symptoms and 57.1% know what can be done to avoid infection; 17.7% declared to have acquired the infection at least once in their lifetime; 62.3% reported total or partial immersion in collections of water of Bananal, once or twice a week, 53.9% of these for bathing or fishing. Although most (91.7%) households have treated running water, are connected to the sewage network or have septic tanks, 9% of the people interviewed use to defecate on the field. It became clear that the educational messages aimed at this population had not been adequate, having failed to fulfil any expectations. The local people received only piecemeal and subjective information about their problem. The control of schistosomiasis requires an integrated practice, which includes the analysis of macro-determinant factors, such as basic sanitation, habitation, education and health care. In short, we require a multidisciplinary vision of the mechanisms of transmission of the infection, which depends upon adequate planning and well trained personnel, intent on their educational work, to attain satisfactory results.