New fecal bacterial signature for colorectal cancer screening reduces the fecal immunochemical test false-positive rate in a screening population

Guidelines recommend routine screening for colorectal cancer (CRC) in asymptomatic adults starting at age 50. The most extensively used noninvasive test for CRC screening is the fecal immunochemical test (FIT), which has an overall sensitivity for CRC of approximately 61.0%-91.0%, which drops to 27.0%-67.0% for advanced adenomas. These figures contain a high false-positive rate and a low positive predictive value. This work aimed to develop a new, noninvasive CRC screening tool based on fecal bacterial markers capable of decreasing FIT false-positive rates in a FIT-positive population. We defined a fecal bacterial signature (RAID-CRC Screen) in a proof-of-concept with 172 FIT-positive individuals and validated the obtained results on an external cohort of 327 FIT-positive subjects. All study participants had joined the national CRC screening program. In the clinical validation of RAID-CRC Screen, a sensitivity of 83.9% and a specificity of 16.3% were obtained for the detection of advanced neoplasm lesions (advanced adenomas and/or CRC). FIT 20 μg/g produced 184 false-positive results. Using RAID-CRC Screen, this value was reduced to 154, thus reducing the false-positive rate by 16.3%. The RAID-CRC Screen test could be implemented in CRC screening programs to allow a significant reduction in the number of colonoscopies performed unnecessarily for FIT-positive participants of CRC screening programs

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Comparação de tratamentos preventivos à calcificação em biomaterial (pericárdio bovino) empregado para a confecção de válvulas cardíacas protéticas

Biopróteses de válvulas cardíacas derivadas de tecidos animais que sofreram ligações cruzadas por ação do glutaraldeído, como o pericárdio bovino, têm uso terapêutico limitado devido ao fato de que tendem a sofrer processo de calcificação. Para prevenir a calcificação, diversas modificações podem ser feitas nos biomateriais; uma das estratégias empregadas é introduzir moléculas volumosas que podem ocupar os espaços entre as estruturas, e por efeito estérico, impedir o crescimento dos cristais de cálcio. Assim o objetivo deste trabalho foi depositar um filme de polímero fluorado (tipo Teflon®), e um filme de carbono amorfo tipo diamante por entre as fibras de colágeno que compõem o pericárdio bovino, e com isso promover um impedimento estérico nos locais onde os cristais de cálcio poderiam se desenvolver. Para tanto, foi empregada a estratégia de deposição de polímero à base de tetrafluoreto de carbono e hidrogênio e de carbono amorfo tipo diamante por plasma. Amostras dos grupos controle, e tratados com os dois processos foram submetidas ao ensaio de citotoxicidade empregando células de fibroblastos de camumdongos, L929, com resultados satisfatórios. A resistência mecânica, também comparativa, foi efetuada e permitiu definir para os dois grupos tratados (polímero à base de tetrafluoreto de carbono e carbono amorfo tipo diamante) respectivamente valor de média geral correspondente a (1,0737 e 0,8565) kgf. A temperatura de encolhimento abrupto das amostras, efetuada como medida do grau de estabilização do colágeno após fixação, e foram verificados valores médios semelhantes entre os dois grupos tratados (90,3 e 90,8)°C e por sua vez superiores aos do controle. As avaliações feitas em microscopia eletrônica de varredura evidenciaram, sob aumento de 372X, superfícies de menor rugosidade para ambos os grupos tratados comparativamente ao controle, característica positiva a princípio na hemocompatibilidade dos materiais. A superfície conseguida após tratamento com tetrafluoreto de carbono mostra-se mais uniforme que aquela submetida ao tratamento com carbono amorfo tipo diamante. As medições de cálcio por absorção atômica mostram diferenças intensas entre os valores medidos para controle, grupos tratados com tetrafluoreto de carbono e carbono amorfo tipo diamante. Os resultados obtidos a partir dos implantes subcutâneos, com tempo total de permanência de 25 dias, permitiram, após coloração de von Kossa, observar intenso contraste entre o grupo controle ( com grosseiro depósito de cálcio) e grupos tratados, praticamente isentos de cálcio, eficácia funcional do tratamento, conforme já permitiam antever os resultados químicos. Ainda na coloração do tricrômio de Masson, permitiu que fosse evidenciada a integridade das fibras de colágeno, corroborando com o resultado mecânico (tração) e físico-químico (encolhimento) anteriormente apresentados. Por sua vez, os resultados da coloração Hematoxilina-Eosina, evidenciando ausência de reações que caracterizam rejeição, degradação, reabsorção ou neovascularização. Portanto, além das vantagens funcionais, os resultados dos testes in vitro e in vivo caracterizam a biocompatibilidade do pericárdio submetido aos tratamentos propostos. Por fim, valorizam a sua adequação, merecendo imediata consideração em aplicações clínico-cirúrgicas, com nítidas vantagens a ambos os processos propostos no aspecto de melhoria funcional. Ainda, entre ambos, evidenciam-se melhores características para o tratado por deposição de polímero à base de tetrafluoreto de carbono.Bioprosthetic cardiac valves derived from glutaraldehyde cross-linked animal tissues, like fixed bovine pericardium, have limited therapeutic uses due to the fact that they tend to undergo a process of calcification. To prevent calcification a variety of modifications can be done to the biomaterials. One strategy is to introduce into biomaterials large molecules that can act as space-fillers, hindering the growth of calcium crystals. Plasma deposition process were used to introduce diamond like carbon and polymer from carbon tetrafluoride and hydrogen into the collagenic fibrous structure of the tissue. Samples of untreated pericardial patches ( control group) and patches treated by plasma deposition of diamond-like carbon and polymer from carbon tetrafluoride were evaluated initially by in vitro citotoxicity test − agar diffusion test with fibroblast cell line L929, showing satisfactory results. Tensile strength was measured and the results were (1,0737 and 0,8565) kgf respectively to tetrafluoride carbon and diamond like carbon groups. The shrinkage temperature was determined and the mean results were similar between the treated groups (90,3 and 90,8)°C, and bigger in both case than control group. The scanning electron microscopy showed at magnification 372X, smoothed surfaces to treated groups when compared to the control one. This fact is positive because increases the biomaterial haemocompatibility. Calcification was assessed by determining the calcium content of the patches using atomic absorption and revealed intensive differences between control and treated groups. From de subcutaneous explanted patches parallel assays were made in search of histopathological changes after implantation. At the von Kossas stain it was possible to observe the intensive contrast between the groups by the gross deposition of calcium to the contrai group, and sparce and scarce calcification in form of dots to the treated ones. At the Masson trichrome stain it was possible to examine the integrity of collagen fibers correlating to the results of mechanical strength and shrinkage temperature. At the hematoxilin-eosin stain it was not seen characteristics reactions of rejection, degradation, resorption or neovascularization. By this way, considering the functional advantages and the very good results obtained it is possible to characterize the biocompatibility of the treated pericardium by both process, increasing the possibility and adequacy of clinical application