Dual endothelin-converting enzyme/neutral endopeptidase blockade in rats with D-galactosamine-induced liver failure

Secondary activation of the endothelin system is thought to be involved in toxic liver injury. This study tested the hypothesis that dual endothelin-converting enzyme / neutral endopeptidase blockade might be able to attenuate acute toxic liver injury

Hormone replacement therapy, mammography screening and changing age-specific incidence rates of breast cancer: an ecological study comparing two European populations

Background: In 2003, for the first time, US breast cancer incidence rates have fallen. Experts argue whether this is due to the reduced uptake of screening mammography or to lower use of Hormone Replacement Therapy (HRT). This study aims to disentangle the respective impact of screening and HRT on age-incidence rates and histology of breast cancer, by comparing two populations with comparably high levels of screening mammography, but with different prevalence of HRT. Methods: We included all invasive breast cancers recorded at the Geneva cancer registry (n=4,909) and the Netherlands Cancer Registry (n=152,428) between 1989-2003. We compared age-specific incidence rates and trends in histological subtyping between the two populations. Results: Between 1989-1991, incidence rates increased with age in both populations. In 2001-2003, women aged 60-64years showed highest incidence rates in Geneva, while in the Netherlands incidence rates continued to increase with age. The annual increase in ductal cancer incidence was similar in the Netherlands (2.3%) and Geneva (2.5%), but the annual increase in lobular cancer was sharper in Geneva (10%) than in the Netherlands (5%). Conclusion: The sharp differences in age distribution and histological subtyping of breast cancer between two European populations are not attributable to screening, since both populations have a high uptake of mammography screening. Since the prevalence of HRT use is very high in Geneva and rather low in the Netherlands, HRT may explain these discrepancies. However, other etiological factors and differences in histological assessment may also have played a rol

Internal avalanches in a pile of superconducting vortices

Using an array of miniature Hall probes, we monitored the spatiotemporal variation of the internal magnetic induction in a superconducting niobium sample during a slow sweep of external magnetic field. We found that a sizable fraction of the increase in the local vortex population occurs in abrupt jumps. The size distribution of these avalanches presents a power-law collapse on a limited range. In contrast, at low temperatures and low fields, huge avalanches with a typical size occur and the system does not display a well-defined macroscopic critical current.Comment: 5 pages including 5 figure

M2 pyruvate kinase provides a mechanism for nutrient sensing and regulation of cell proliferation

We show that the M2 isoform of pyruvate kinase (M2PYK) exists in equilibrium between monomers and tetramers regulated by allosteric binding of naturally occurring small-molecule metabolites. Phenylalanine stabilizes an inactive T-state tetrameric conformer and inhibits M2PYK with an IC(50) value of 0.24 mM, whereas thyroid hormone (triiodo-l-thyronine, T3) stabilizes an inactive monomeric form of M2PYK with an IC(50) of 78 nM. The allosteric activator fructose-1,6-bisphosphate [F16BP, AC(50) (concentration that gives 50% activation) of 7 μM] shifts the equilibrium to the tetrameric active R-state, which has a similar activity to that of the constitutively fully active isoform M1PYK. Proliferation assays using HCT-116 cells showed that addition of inhibitors phenylalanine and T3 both increased cell proliferation, whereas addition of the activator F16BP reduced proliferation. F16BP abrogates the inhibitory effect of both phenylalanine and T3, highlighting a dominant role of M2PYK allosteric activation in the regulation of cancer proliferation. X-ray structures show constitutively fully active M1PYK and F16BP-bound M2PYK in an R-state conformation with a lysine at the dimer-interface acting as a peg in a hole, locking the active tetramer conformation. Binding of phenylalanine in an allosteric pocket induces a 13° rotation of the protomers, destroying the peg-in-hole R-state interface. This distinct T-state tetramer is stabilized by flipped out Trp/Arg side chains that stack across the dimer interface. X-ray structures and biophysical binding data of M2PYK complexes explain how, at a molecular level, fluctuations in concentrations of amino acids, thyroid hormone, and glucose metabolites switch M2PYK on and off to provide the cell with a nutrient sensing and growth signaling mechanism

Two noteworthy Calea (Asteraceae: Neurolaeneae) from contact areas of the Atlantic Forest and Cerrado of Brazil.

Systematic studies in the Calea myrtifolia complex have revealed two noteworthy new taxa from the contact, relict and transitional areas of the Atlantic Forest and Cerrado domains in Brazil: Calea grandiflora and Calea × parviantha, both having been treated as C. myrtifolia, now considered endemic to Minas Gerais state, Brazil. Thus, we herein provide morphological descriptions, illustrations, geographical distribution maps and discuss their taxonomic affinities. Moreover, their potential distributions are predicted. Calea grandiflora is related to C. arachnoidea and is recognized by the basal acrodromous venation (vs. semicraspedodromous), outer phyllary series 12.2?20 × 4.2?10.6 mm long (vs. 9?12 × 3?5 mm), and ray floret corolla 16.9?31 mm long (vs. 10?12 mm). Calea × parviantha is a new nothospecies, supported by a unique set of character states partially shared with the parental species C. parvifolia and C. triantha. The new hybrid species has intermediate morphology, as demonstrated by a multivariate analysis. It differs from C. parvifolia by the hispid, hispidulous or glabrous stems (vs. puberulous or puberulent) and coriaceous leaves (vs. chartaceous leaves), and from C. triantha by the rounded leaf base, sometimes subcordate (vs. cordate) and pappus scales 1.1?2.7 mm long (vs. 0.8?1.3 mm). Furthermore, we provide a taxonomic key for Calea in the states of São Paulo and Paraná

An Evaluation of Agreement of Breathing Rates Measured by a Novel Device, Manual Counting, and Other Techniques Used in Clinical Practice: Protocol for the Observational VENTILATE Study.

BACKGROUND: Respiratory rate (RR) is the most sensitive physiological observation to predict clinical deterioration on hospital wards, and poor clinical monitoring has been highlighted as a primary contributor to avoidable mortality. Patients in intensive care have their RR monitored continuously, but this equipment is rarely available on general hospital wards. OBJECTIVE: The primary objective is to assess the accuracy of the RespiraSense device in comparison with other methods currently used in clinical practice. The secondary objective is to assess the accuracy of the RespiraSense device in participants in different positions and when reading aloud. METHODS: A single-center, prospective observational study will investigate the agreement of the RespiraSense device as compared with other device measurements (capnography, electrocardiogram) and the current standard measurement of RR (manual counting by a trained health care professional). The different methods will be employed concurrently on the same participant as part of a single study visit. RESULTS: Recruitment to this study has not yet started as funding decisions are still pending. Therefore, results are not available at this stage. It is anticipated that the data required could be collected within 2 months of first recruitment to the study and data analysis completed within 6 months of the study start date. CONCLUSIONS: The Evaluation of Agreement of Breathing Rates Measured by a Novel Device, Manual Counting, and Other Techniques Used in Clinical Practice (VENTILATE) study will provide further validation of the use of the RespiraSense device in subjects with abnormal respiratory rates. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/15437