Comparison between SeHCAT test and clinical response to cholestyramine in patients with chronic diarrhea and high suspicion of bile acid malabsorption: A single-center prospective study.

OBJECTIVES: We aimed to evaluate the clinical response to cholestyramine in patients with functional chronic diarrhea and a high clinical suspicion of bile-acid diarrhea (BAD) investigated with 75-selenium homocholic acid taurine (SeHCAT) test. METHODS: Adult patients attending our outpatient clinic between January and December 2021 for chronic diarrhea with suspicion of BAD were proposed SeHCAT testing and a therapeutic trial of cholestyramine 4-8 g daily. Clinical response to cholestyramine was evaluated at 1, 3, 6, and 12 months. Clinical and demographic data were analyzed according to SeHCAT test results. RESULTS: Among the 50 patients with chronic diarrhea and clinical suspicion of BAD, 13 (26.0%) refused either SeHCAT testing or cholestyramine therapy. Finally, 37 patients (31 females, age 44 ± 14 years) agreed to undergo SeHCAT and were started on cholestyramine (median follow-up 14 months [interquartile range 6-16 months]). Initial response to cholestyramine was similar in patients with positive and negative SeHCAT test results, but improved over time in those with a positive test result. Long-term response (100% vs 65.2%, P = 0.02) and necessity of maintenance therapy for symptom control were more common in those with positive SeHCAT test result (71.4% vs 26.1%, P = 0.02). However, response to cholestyramine was also frequent in patients with a negative test result. CONCLUSIONS: The SeHCAT test accurately identifies patients with BAD who benefit from long-term cholestyramine treatment. Nevertheless, cholestyramine may be also effective in patients with chronic diarrhea but negative SeHCAT test result.

A tri-modal tissue-equivalent anthropomorphic phantom for PET, CT and multi-parametric MRI radiomics.

PURPOSE: Radiomics has emerged as an advanced image processing methodology to define quantitative imaging biomarkers for prognosis and prediction of treatment response and outcome. The development of quantitative imaging biomarkers requires careful analysis to define their accuracy, stability and reproducibility through phantom measurements. Few efforts were devoted to develop realistic anthropomorphic phantoms. In this work, we developed a multimodality image phantom suitable for PET, CT and multiparametric MRI imaging. METHODS: A tissue-equivalent gel-based mixture was designed and tested for compatibility with different imaging modalities. Calibration measurements allowed to assess gel composition to simulate PET, CT and MRI contrasts of oncological lesions. The characterized gel mixture was used to create realistic synthetic lesions (e.g. lesions with irregular shape and non-uniform image contrast), to be inserted in a standard anthropomorphic phantom. In order to show phantom usefulness, issues related to accuracy, stability and reproducibility of radiomic biomarkers were addressed as proofs-of-concept. RESULTS: The procedure for gel preparation was straightforward and the characterized gel mixture allowed to mime simultaneously oncological lesion contrast in CT, PET and MRI imaging. Proofs-of-concept studies suggested that phantom measurements can be customized for specific clinical situations and radiomic protocols. CONCLUSIONS: We developed a strategy to manufacture an anthropomorphic, tissue-equivalent, multimodal phantom to be customized on specific radiomics protocols, for addressing specific methodological issues both in mono and multicentric studies.

A distinct complex of PRP19-related and trypanosomatid-specific proteins is required for pre-mRNA splicing in trypanosomes.

The pre-mRNA splicing factor PRP19 is recruited into the spliceosome after forming the PRP19/CDC5L complex in humans and the Nineteen complex in yeast. Additionally, 'PRP19-related' proteins enter the spliceosome individually or in pre-assemblies that differ in these systems. The protistan family Trypanosomatidae, which harbors parasites such as Trypanosoma brucei, diverged early during evolution from opisthokonts. While introns are rare in these organisms, spliced leader trans splicing is an obligatory step in mRNA maturation. So far, ∼70 proteins have been identified as homologs of human and yeast splicing factors. Moreover, few proteins of unknown function have recurrently co-purified with splicing proteins. Here we silenced the gene of one of these proteins, termed PRC5, and found it to be essential for cell viability and pre-mRNA splicing. Purification of PRC5 combined with sucrose gradient sedimentation revealed a complex of PRC5 with a second trypanosomatid-specific protein, PRC3, and PRP19-related proteins SYF1, SYF3 and ISY1, which we named PRP19-related complex (PRC). Importantly, PRC and the previously described PRP19 complex are distinct from each other because PRC, unlike PRP19, co-precipitates U4 snRNA, which indicates that PRC enters the spliceosome prior to PRP19 and uncovers a unique pre-organization of these proteins in trypanosomes.

Parameters Influencing PET Imaging Features: A Phantom Study with Irregular and Heterogeneous Synthetic Lesions.

Aim: To evaluate reproducibility and stability of radiomic features as effects of the use of different volume segmentation methods and reconstruction settings. The potential of radiomics in really capturing the presence of heterogeneous tumor uptake and irregular shape was also investigated. Materials and Methods: An anthropomorphic phantom miming real clinical situations including synthetic lesions with irregular shape and nonuniform radiotracer uptake was used. 18F-FDG PET/CT measurements of the phantom were performed including 38 lesions of different shape, size, lesion-to-background ratio, and radiotracer uptake distribution. Different reconstruction parameters and segmentation methods were considered. COVs were calculated to quantify feature variations over the different reconstruction settings. Friedman test was applied to the values of the radiomic features obtained for the considered segmentation approaches. Two sets of test-retest measurement were acquired and the pairwise intraclass correlation coefficient was calculated. Fifty-eight morphological and statistical features were extracted from the segmented lesion volumes. A Mann-Whitney test was used to evaluate significant differences among each feature when calculated from heterogeneous versus homogeneous uptake. The significance of each radiomic feature in terms of capturing heterogeneity was evaluated also by testing correlation with gold standard indexes of heterogeneity and sphericity. Results: The choice of the segmentation method has a strong impact on the stability of radiomic features (less than 20% can be considered stable features). Reconstruction affects the estimate of radiomic features (only 26% are stable). Thirty-one radiomic features (53%) resulted to be reproducible, 11 of them are able to discriminate heterogeneity. Among these, we found a subset of 3 radiomic features strongly correlated with GS heterogeneity index that can be suggested as good features for retrospective evaluations.

Neurospora crassa developmental control mediated by the FLB-3 transcription factor.

Here, we report that the Neurospora crassa FLB-3 protein, the ortholog of the Aspergillus nidulans FlbC transcription factor, is required for developmental control. Deletion of flb-3 leads to changes in hyphae morphology and affects sexual and asexual development. We identified, as putative FLB-3 targets, the N. crassa aba-1, wet-1 and vos-1 genes, orthologs of the ones involved in A. nidulans asexual development and that work downstream of FlbC (abaA, wetA and vosA). In N. crassa, these three genes require FLB-3 for proper expression; however, they appear not to be required for normal development, as demonstrated by gene expression analyses during vegetative growth and asexual development. Moreover, mutant strains in the three genes conidiate well and produce viable conidia. We also determined FLB-3 DNA-binding preferences via protein-binding microarrays (PBMs) and demonstrated by chromatin immunoprecipitation (ChIP) that FLB-3 binds the aba-1, wet-1 and vos-1 promoters. Our data support an important role for FLB-3 in N. crassa development and highlight differences between the regulatory pathways controlled by this transcription factor in different fungal species.

Intervenções cognitivas e comportamentais para manejo de insônia em pacientes oncológicos / Cognitive and behavioural interventions for insomnia management in cancer patients / Intervenciones cognitivas y conductuales para el manejo de insomnio en pacientes oncológicos

Introdução: A prevalência de insônia em pacientes oncológicos oscila de 30 a 50%. As psicoterapias cognitivo-comportamentais apresentam eficácia comprovada para o tratamento desta condição. Objetivos: Identificar as principais intervenções cognitivas e comportamentais para manejo de insônia no contexto oncológico. Método: Realizar uma revisão sistemática da literatura produzida entre os anos de 2010 e 2015 nas bases: Pubmed Psych Info e Google Scholar. Foram utilizados os seguintes descritores: Insomnia, Cancer, Cognitive Behavioral Therapy, Randomized Controlled Trial. A qualidade metodológica dos artigos encontrados foi avaliada através da escala JADAD. Resultados: Intervenções cognitivo-comportamentais, incluindo Mindfulness, apresentam evidências de eficácia em pacientes oncológicos, com peculiaridades que devem ser consideradas pelos profissionais no momento da escolha da intervenção. Considerações Finais: Há necessidade de maior apropriação das técnicas por parte dos profissionais envolvidos na atenção em saúde mental no contexto oncológico. Ainda, novas pesquisas devem ser realizadas para verificação de eficácia considerando aspectos socioculturais da população brasileira.

Introduction: The prevalence of insomnia in cancer patients ranges between 30 and 50%. Cognitive Behavioral psychotherapies have proven effective for treating insomnia. Objectives: Identify the main cognitive and behavioral interventions for insomnia management in the oncological context. Method: A systematic review of the literature produced between 2010 and 2015 was conducted based on: PsychInfo PubMed and Google Scholar. The following words were researched: Insomnia, Cancer, Cognitive Behavioral Therapy, and Randomized Controlled Trial. Methodological quality was assessed by JADAD scale by two independent evaluators. Results: The results in articles surveyed indicate that cognitive behavioral interventions, including Mindfulness, show evidence of effectiveness in cancer patients with peculiarities that must be considered by professionals when choosing the intervention. Conclusion: There is a need for mental health care professionals to fully grasp the techniques in order to work with oncological patients. More research is to be carried out to verify the effectiveness considering socio-cultural aspects of the Brazilian population.

Introducción: La prevalencia del insomnio en pacientes oncológicos varia de 30 a 50%. Las psicoterapias cognitivo-conductuales presentan una eficacia comprobada para el tratamiento de esta condición. Objetivo: Identificar las principales intervenciones cognitivas y conductuales para el manejo del insomnio en el contexto oncológico. Método: Realizar una revisión sistemática de la literatura producida entre los años 2010 y 2015 en las bases: Pubmed PsychInfo y Google Scholar. Fueron utilizados los siguientes descriptores: "Insomnia", "Cancer", "Cognitive Behavioral Therapy", "Randomized Controlled Trial". La calidad metodológica de los artículos encontrados fue evaluada a través de la escala JADAD. Resultados: Intervenciones cognitivo-conductuales, incluyendo Mindfulness, presentan evidencias de eficacia en pacientes oncológicos, con peculiaridades que deben ser consideradas por los profesionales en el momento de la elección de la intervención. Consideraciones finales: Hay necesidad de mayor apropiación de las técnicas por parte de los profesionales involucrados en la atención en salud mental en el contexto oncológico. Así como, nuevas investigaciones deben ser realizadas con el fin de verificar la eficacia, considerando aspectos socioculturales de la población brasileña.

A Method for Manufacturing Oncological Phantoms for the Quantification of 18F-FDG PET and DW-MRI Studies.

The aim of this work was to develop a method to manufacture oncological phantoms for quantitation purposes in 18F-FDG PET and DW-MRI studies. Radioactive and diffusion materials were prepared using a mixture of agarose and sucrose radioactive gels. T2 relaxation and diffusion properties of gels at different sucrose concentrations were evaluated. Realistic oncological lesions were created using 3D-printed plastic molds filled with the gel mixture. Once solidified, gels were extracted from molds and immersed in a low-radioactivity gel simulating normal background tissue. A breast cancer phantom was manufactured using the proposed method as an exploratory feasibility study, including several realistic oncological configurations in terms of both radioactivity and diffusion. The phantom was acquired in PET with 18F-FDG, immediately after solidification, and in DW-MRI the following day. Functional volumes characterizing the simulated BC lesions were segmented from PET and DW-MRI images. Measured radioactive uptake and ADC values were compared with gold standards. Phantom preparation was straightforward, and the time schedule was compatible with both PET and MRI measurements. Lesions appeared on 18F-FDG PET and DW-MRI images as expected, without visible artifacts. Lesion functional parameters revealed the phantom's potential for validating quantification methods, in particular for new generation hybrid PET-MRI systems.

Regulation of the reserve carbohydrate metabolism by alkaline pH and calcium in Neurospora crassa reveals a possible cross-regulation of both signaling pathways.

BACKGROUND: Glycogen and trehalose are storage carbohydrates and their levels in microorganisms vary according to environmental conditions. In Neurospora crassa, alkaline pH stress highly influences glycogen levels, and in Saccharomyces cerevisiae, the response to pH stress also involves the calcineurin signaling pathway mediated by the Crz1 transcription factor. Recently, in yeast, pH stress response genes were identified as targets of Crz1 including genes involved in glycogen and trehalose metabolism. In this work, we present evidence that in N. crassa the glycogen and trehalose metabolism is modulated by alkaline pH and calcium stresses. RESULTS: We demonstrated that the pH signaling pathway in N. crassa controls the accumulation of the reserve carbohydrates glycogen and trehalose via the PAC-3 transcription factor, which is the central regulator of the signaling pathway. The protein binds to the promoters of most of the genes encoding enzymes of glycogen and trehalose metabolism and regulates their expression. We also demonstrated that the reserve carbohydrate levels and gene expression are both modulated under calcium stress and that the response to calcium stress may involve the concerted action of PAC-3. Calcium activates growth of the Δpac-3 strain and influences its glycogen and trehalose accumulation. In addition, calcium stress differently regulates glycogen and trehalose metabolism in the mutant strain compared to the wild-type strain. While glycogen levels are decreased in both strains, the trehalose levels are significantly increased in the wild-type strain and not affected by calcium in the mutant strain when compared to mycelium not exposed to calcium. CONCLUSIONS: We previously reported the role of PAC-3 as a transcription factor involved in glycogen metabolism regulation by controlling the expression of the gsn gene, which encodes an enzyme of glycogen synthesis. In this work, we extended the investigation by studying in greater detail the effects of pH on the metabolism of the reserve carbohydrate glycogen and trehalose. We also demonstrated that calcium stress affects the reserve carbohydrate levels and the response to calcium stress may require PAC-3. Considering that the reserve carbohydrate metabolism may be subjected to different signaling pathways control, our data contribute to the understanding of the N. crassa responses under pH and calcium stresses.

Eribulin across multiple lines of chemotherapy: a retrospective study on quality of life and efficacy in metastatic breast cancer patients.

This study evaluates efficacy, tolerability and health-related quality of life of eribulin in patients with metastatic breast cancer. Predictive and/or prognostic factors of outcome were also analyzed. Among 44 women receiving eribulin mesylate, one patient had a complete response, 22.7% a partial response and 25% a stable disease. Median overall survival and median progression-free survival were 11.8 and 4.5 months, respectively. Treatment was well tolerated; the most frequent adverse events were neutropenia (52%), leukopenia (50%), fatigue (38%) and alopecia (40%). No significant reductions of health-related quality of life parameters were observed. Disease control during previous chemotherapy lines was related with better outcome with eribulin. In conclusion, eribulin treatment should be considered in a multiple chemotherapy lines strategy in metastatic breast cancer.

Oleanonic acid from Lippia lupulina (Verbenaceae) shows strong in vitro antileishmanial and antitrypanosomal activity / Ácido oleanônico isolado de Lippia lupulina (Verbenaceae) apresenta potentes atividades leishmanicida e tripanocida

Leishmaniasis and Chagas disease affect millions of people in tropical and subtropical regions. Drugs used currently to treat such diseases often present undesirable side effects and low efficiency. The aim of this work was to identify extracts and isolated compounds from the genus Lippia with leishmanicidal and trypanocidal activity. Fifteen extracts from different plant parts of Lippia species with partially known chemical compositions, four partition fractions, six compounds and a mixture of four interconverting flavanones previously isolated from Lippia salviaefolia and Lippia lupulina were assayed in vitro towards epimastigote forms of Trypanosoma cruzi and promastigote forms of Leishmania amazonensis. The root extract of L. lupulina had potent activity against T. cruzi and L. amazonensis (IC50 of 20.0 and 54.5 µg mL-1, respectively). The triterpenoid oleanonic acid showed the strongest activity against these protozoans (IC50 of 18.5 and 29.9 µM, respectively). Our results indicate that Lippia plants and their derivatives deserve further investigation in the search for new antiprotozoal drugs, particularly for the treatment of leishmaniasis and Chagas disease.

Leishmaniose e doença de Chagas afetam milhões de pessoas em regiões tropicais e subtropicais. As drogas atualmente usadas para tratar estas doenças frequentemente apresentam efeitos colaterais indesejáveis e baixa eficiência. Este trabalho teve como objetivo encontrar extratos, frações e compostos isolados de espécies do gênero Lippia com atividades leishmanicida e tripanocida. Quinze extratos de diferentes partes de plantas do gênero Lippia, com composições químicas parcialmente conhecidas, quatro frações de partição, seis substâncias e uma mistura de quatro flavanonas interconversíveis isolados de Lippia salviaefolia e Lippia lupulina foram testados, in vitro, frente a formas epimastigotas de Trypanosoma cruzi e promastigotas de Leishmania amazonensis. O extrato etanólico das raízes de L. lupulina apresentou atividade potente contra T. cruzi e L. amazonensis (IC50 de 20,0 e 54,5 µg mL-1, respectivamente), enquanto que o ácido oleanônico mostrou as atividades mais fortes contra estes protozoários, com IC50 de 18,5 e 29,9 µM, respectivamente. Estes resultados indicam que espécies do gênero Lippia e seus derivados merecem investigações adicionais na busca por novas terapias antiprotozoárias, especialmente para o tratamento de leishmaniose e doença de Chagas.

Cyclin-Dependent Kinase CRK9, Required for Spliced Leader trans Splicing of Pre-mRNA in Trypanosomes, Functions in a Complex with a New L-Type Cyclin and a Kinetoplastid-Specific Protein.

In eukaryotes, cyclin-dependent kinases (CDKs) control the cell cycle and critical steps in gene expression. The lethal parasite Trypanosoma brucei, member of the phylogenetic order Kinetoplastida, possesses eleven CDKs which, due to high sequence divergence, were generically termed CDC2-related kinases (CRKs). While several CRKs have been implied in the cell cycle, CRK9 was the first trypanosome CDK shown to control the unusual mode of gene expression found in kinetoplastids. In these organisms, protein-coding genes are arranged in tandem arrays which are transcribed polycistronically. Individual mRNAs are processed from precursor RNA by spliced leader (SL) trans splicing and polyadenylation. CRK9 ablation was lethal in cultured trypanosomes, causing a block of trans splicing before the first transesterification step. Additionally, CRK9 silencing led to dephosphorylation of RNA polymerase II and to hypomethylation of the SL cap structure. Here, we tandem affinity-purified CRK9 and, among potential CRK9 substrates and modifying enzymes, discovered an unusual tripartite complex comprising CRK9, a new L-type cyclin (CYC12) and a protein, termed CRK9-associated protein (CRK9AP), that is only conserved among kinetoplastids. Silencing of either CYC12 or CRK9AP reproduced the effects of depleting CRK9, identifying these proteins as functional partners of CRK9 in vivo. While mammalian cyclin L binds to CDK11, the CRK9 complex deviates substantially from that of CDK11, requiring CRK9AP for efficient CRK9 complex formation and autophosphorylation in vitro. Interference with this unusual CDK rescued mice from lethal trypanosome infections, validating CRK9 as a potential chemotherapeutic target.

Haemostasis monitored in stored red blood cells, plasma and platelet concentrates in the proportion of 4 :  4 :  1 diluted with crystalloids and colloids.

The aim of this in-vitro study was to evaluate haemostasis analysed with thromboelastometry and blood gas and blood count variables, in stored blood components and the effects after dilution with Ringer[Combining Acute Accent]s acetate, albumin and hydroxyethyl starch (HES). Aliquots from stored red blood cells, plasma and platelet concentrates were mixed in the proportion of 4 : 4 : 1 and analysed with rotational thromboelastometry (ROTEM), blood count [haemoglobin (Hb), haematocrit, platelet count] and blood gas (pH, calcium, sodium, potassium, glucose levels). The blood mix was thereafter diluted 20 and 33% with Ringer's acetate, albumin or HES. The stored blood component mix in a ratio of 4 : 4 : 1 had a low pH (7.11 ±â€Š0.03, mean ±â€Šstandard deviation), nonmeasurable calcium level, and high concentrations of sodium, potassium and glucose but ROTEM curves within normal range after recalcification. With Ringer's acetate dilution, the ROTEM variables changed almost linearly with increasing dilution volume. When albumin was used in the 33% dilution, the clot firmness of the fibrin clot (FibTEM) was further reduced, and with HES dilution, there was a pronounced impairment. The stored blood mix had a low pH and calcium level, both of which might have a significant influence on the coagulation process but normal ROTEM curves after recalcification. Dilution with Ringer's acetate and albumin resulted in moderate deterioration, while dilution with HES showed severely impaired haemostasis.

[Social support to women after mastectomy: a review study]. / Apoio social à mulher mastectomizada: um estudo de revisão.

It is necessary to understand how social support can contribute to minimize the impact of the diagnosis and treatment of mammary tumors in order to underpin the actions of comprehensive women's health care. This study seeks to analyze the contribution of the national and international literature regarding the perceived social support by women diagnosed with breast cancer. Twelve studies were selected from the MedLine, Lilacs and PsycINFO databases over a 10-year period (2000-2010) with pre-defined criteria for inclusion. The results were organized into thematic categories: the perception of family support; perceived social support; the perception of educational support; the need to improve the research and the assistance given to women after mastectomy and their families. The studies dedicated to the subjective dimension of social support are still incipient. The available evidence suggests that the literature is limited to topics of interest to the traditional health professions, such as Nursing and Medicine, focusing on constructs that can be directly quantified. The concern with social support must be present from the time of diagnosis to psychosocial rehabilitation, as part of the process of tackling the situation.

Apoio social à mulher mastectomizada: um estudo de revisão / Social support to women after mastectomy: a review study

Para fundamentar as ações de cuidado integralizado em saúde da mulher é necessário compreender de que modo o apoio social pode contribuir para minimizar as repercussões do diagnóstico e do tratamento da neoplasia mamária. O objetivo deste estudo é analisar a contribuição da produção científica nacional e internacional acerca do apoio social percebido por mulheres diagnosticadas com câncer de mama. A amostra foi constituída de 12 publicações, obtidas a partir de critérios de inclusão preestabelecidos, nas bases de dados MedLine, Lilacs e PsycINFO, na última década (2000-2010). Os resultados foram sistematizados em categorias temáticas: percepção do apoio familiar, apoio social percebido, percepção do apoio educacional, necessidade de aprimoramento da pesquisa e assistência às mastectomizadas e suas famílias. Os estudos dedicados à dimensão subjetiva do apoio social ainda são incipientes. As evidências disponíveis sugerem que a literatura é circunscrita a temas de interesse das profissões tradicionais da área da saúde, como Enfermagem e Medicina, privilegiando construtos que podem ser diretamente quantificados. A preocupação com o apoio social deve estar presente desde a fase de diagnóstico até a reabilitação psicossocial, como parte do processo de enfrentamento.

It is necessary to understand how social support can contribute to minimize the impact of the diagnosis and treatment of mammary tumors in order to underpin the actions of comprehensive women's health care. This study seeks to analyze the contribution of the national and international literature regarding the perceived social support by women diagnosed with breast cancer. Twelve studies were selected from the MedLine, Lilacs and PsycINFO databases over a 10-year period (2000-2010) with pre-defined criteria for inclusion. The results were organized into thematic categories: the perception of family support; perceived social support; the perception of educational support; the need to improve the research and the assistance given to women after mastectomy and their families. The studies dedicated to the subjective dimension of social support are still incipient. The available evidence suggests that the literature is limited to topics of interest to the traditional health professions, such as Nursing and Medicine, focusing on constructs that can be directly quantified. The concern with social support must be present from the time of diagnosis to psychosocial rehabilitation, as part of the process of tackling the situation.

The spliceosomal PRP19 complex of trypanosomes.

In trypanosomes, mRNAs are processed by spliced leader (SL) trans splicing, in which a capped SL, derived from SL RNA, is spliced onto the 5' end of each mRNA. This process is mediated by the spliceosome, a large and dynamic RNA-protein machinery consisting of small nuclear ribonucleoproteins (snRNPs) and non-snRNP proteins. Due to early evolutionary divergence, the amino acid sequences of trypanosome splicing factors exhibit limited similarity to those of their eukaryotic orthologs making their bioinformatic identification challenging. Most of the ~ 60 protein components that have been characterized thus far are snRNP proteins because, in contrast to individual snRNPs, purification of intact spliceosomes has not been achieved yet. Here, we characterize the non-snRNP PRP19 complex of Trypanosoma brucei. We identified a complex that contained the core subunits PRP19, CDC5, PRL1, and SPF27, as well as PRP17, SKIP and PPIL1. Three of these proteins were newly annotated. The PRP19 complex was associated primarily with the activated spliceosome and, accordingly, SPF27 silencing blocked the first splicing step. Interestingly, SPF27 silencing caused an accumulation of SL RNA with a hypomethylated cap that closely resembled the defect observed previously upon depletion of the cyclin-dependent kinase CRK9, indicating that both proteins may function in spliceosome activation.

Restaging clear cell renal carcinoma with 18F-FDG PET/CT.

AIM: The aim of our retrospective study was to assess the usefulness of F-FDG PET/CT in the restaging of clear cell renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: Sixty-nine patients (median age = 62 years; range = 36-86 years) affected by clear cell RCC (TNM at staging: T1, 42 patients; T2, 13 patients; T3, 11 patients; T4, 3 patients; Fuhrman grade: G2, 47 patients; G3, 20 patients; G4, 2 patients) underwent whole-body F-FDG PET/CT to restage the disease after nephrectomy for clinical or radiological suspicion of metastases. Areas of abnormal uptake at PET/CT were classified, taking the liver uptake as reference, as follows: 1 = faint uptake, lower than liver; 2 = moderate uptake, equal to liver; and 3 = high uptake, higher than liver. Validation of F-FDG PET/CT results was established by (1) biopsy (23 patients) and (2) other imaging modalities (addressed BS; c.e.CT; MRI; F-fluoride PET/CT; subsequent F-FDG PET/CT), and/or clinical and radiological follow-up of 12 months (46 patients). RESULTS: F-FDG PET/CT was positive in 42 patients and negative in 27 patients. Sixteen patients presented single lesions and 26 patients presented multiple localizations of the disease. On a patient basis, 40 patients resulted true positive, 2 patient false positive, 23 patients true negative, and 4 patients false negative. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 90%, 92%, 91%, 95%, and 85%, respectively. On a lesion basis, PET/CT detected 114 areas of abnormal uptake in 42 positive patients of which 112 resulted to be true positive. FDG uptake of the true positive lesions resulted to be high in 83 cases, moderate in 17 lesions, and finally faint in 12 lesions. CONCLUSIONS: F-FDG PET/CT demonstrated a good sensitivity in the restaging of clear cell RCC. Most of the lesions showed intense activity. According to our results, it seems that the use of F-FDG PET/CT in the restaging of RCC is feasible because the number of false-negative cases is limited.

Evolutionary relationships of the Triatoma matogrossensis subcomplex, the endemic triatoma in Central-Western Brazil, based on mitochondrial DNA sequences.

The phylogenetic relationships among species of Triatoma matogrossensis subcomplex (T. baratai, T. guazu, T. matogrossensis, T. sordida, T. vandae, and T. williami) was addressed by using fragments of cytochrome oxidase I (COI), 16S rDNA (16S), and cytochrome b (Cytb) through Bayesian and parsimony analyses. We did not recover a monophyletic T. matogrossensis subcomplex, and their members were found clustered in three strongly supported clades, as follows: i) T. jurbergi + T. matogrossensis + T. vandae + T. garciabesi + T. sordida; ii) with T. guasayana as the sister group of clade (i); and iii) T. williami + T. guazu, however not closely related to the clade formed by the previously mentioned species. The other two endemic species from Central-Western Brazil, T. baratai and T. costalimai, were not recovered with strong clade support as related to other members of this subcomplex. Results call for a further revision in the classification of the subcomplexes within the genus Triatoma.

Attenuation correction for small animal PET images: a comparison of two methods.

In order to extract quantitative parameters from PET images, several physical effects such as photon attenuation, scatter, and partial volume must be taken into account. The main objectives of this work were the evaluation of photon attenuation in small animals and the implementation of two attenuation correction methods based on X-rays CT and segmentation of emission images. The accuracy of the first method with respect to the beam hardening effect was investigated by using Monte Carlo simulations. Mouse- and rat-sized phantoms were acquired in order to evaluate attenuation correction in terms of counts increment and recovery of uniform activity concentration. Both methods were applied to mice and rat images acquired with several radiotracers such as(18)F-FDG, (11)C-acetate, (68)Ga-chloride, and (18)F-NaF. The accuracy of the proposed methods was evaluated in heart and tumour tissues using (18)F-FDG images and in liver, kidney, and spinal column tissues using (11)C-acetate, (68)Ga-chloride, and (18)F-NaF images, respectively. In vivo results from animal studies show that, except for bone scans, differences between the proposed methods were about 10% in rats and 3% in mice. In conclusion, both methods provide equivalent results; however, the segmentation-based approach has several advantages being less time consuming and simple to implement.