Some Like It Fat: Comparative Ultrastructure of the Embryo in Two Demosponges of the Genus Mycale (Order Poecilosclerida) from Antarctica and the Caribbean

0000-0002-7993-1523© 2015 Riesgo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License [4.0], which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

Modeling healthcare authorization and claim submissions using the openEHR dual-model approach

<p>Abstract</p> <p>Background</p> <p>The TISS standard is a set of mandatory forms and electronic messages for healthcare authorization and claim submissions among healthcare plans and providers in Brazil. It is not based on formal models as the new generation of health informatics standards suggests. The objective of this paper is to model the TISS in terms of the openEHR archetype-based approach and integrate it into a patient-centered EHR architecture.</p> <p>Methods</p> <p>Three approaches were adopted to model TISS. In the first approach, a set of archetypes was designed using ENTRY subclasses. In the second one, a set of archetypes was designed using exclusively ADMIN_ENTRY and CLUSTERs as their root classes. In the third approach, the openEHR ADMIN_ENTRY is extended with classes designed for authorization and claim submissions, and an ISM_TRANSITION attribute is added to the COMPOSITION class. Another set of archetypes was designed based on this model. For all three approaches, templates were designed to represent the TISS forms.</p> <p>Results</p> <p>The archetypes based on the openEHR RM (Reference Model) can represent all TISS data structures. The extended model adds subclasses and an attribute to the COMPOSITION class to represent information on authorization and claim submissions. The archetypes based on all three approaches have similar structures, although rooted in different classes. The extended openEHR RM model is more semantically aligned with the concepts involved in a claim submission, but may disrupt interoperability with other systems and the current tools must be adapted to deal with it.</p> <p>Conclusions</p> <p>Modeling the TISS standard by means of the openEHR approach makes it aligned with ISO recommendations and provides a solid foundation on which the TISS can evolve. Although there are few administrative archetypes available, the openEHR RM is expressive enough to represent the TISS standard. This paper focuses on the TISS but its results may be extended to other billing processes. A complete communication architecture to simulate the exchange of TISS data between systems according to the openEHR approach still needs to be designed and implemented.</p

Clinical characteristics associated with the severity of Clostridium [Clostridioides] difficile infection in a tertiary teaching hospital from Mexico

Background: Clostridium difficile infection (CDI) is a leading cause of healthcare-associated diarrhea worldwide. In this study, risk factors associated with the development of severe-complicated and recurrent outcomes in CDI patients in different age groups, including the non-elderly, were assessed in a third-level hospital. Methods: CDI cases were detected by clinical data and polymerase-chain-reaction (PCR). Clinical, demographic, epidemiological, and microbiological risk factors for CDI were evaluated. Results: During the study period, 248 out of 805 patients with nosocomial diarrhea were diagnosed with CDI and the majority were severe-complicated cases (87.90%). Female gender (OR 3.19, 95% CI 1.19e8.55, p ¼ 0.02) and lymphoma (OR 3.95, 95% CI 1.03e15.13, p ¼ 0.04) were risk factors for severe-complicated CDI. Mature adulthood (51e60 years) (OR 5.80, 95% CI 1.56e21.62, p ¼ 0.01), previous rifampicin use (OR 7.44, 95% CI 2.10e26.44, p ¼ 0.00), and neoplasm (solid malignant neoplasm or hematological malignancies) (OR 4.12, 95% CI 1.01e16.83, p ¼ 0.04) were risk factors for recurrent infection. Autoimmune disorders (OR 6.62, CI 95% 1.26e34.73, p ¼ 0.02), leukemia (OR 4.97, 95% CI 1.05e23.58, p ¼ 0.04), lymphoma (OR 3.79, 95% CI 1.03e12.07, p ¼ 0.04) and previous colistin treatment (OR 4.97, 95% CI 1.05e23.58, p ¼ 0.04) were risk factors for 30-day mortality. Conclusion: Newly identified risk factors for recurrent CDI were rifampicin treatment and age between 51 and 60 years; colistin treatment was identified as a risk factor for 30-day mortality. Previously identified risk factors for severe-complicated CDI were confirmed, but with a major impact on non-elderly patients

A BAX/BAK and Cyclophilin D-Independent Intrinsic Apoptosis Pathway

Most intrinsic death signals converge into the activation of pro-apoptotic BCL-2 family members BAX and BAK at the mitochondria, resulting in the release of cytochrome c and apoptosome activation. Chronic endoplasmic reticulum (ER) stress leads to apoptosis through the upregulation of a subset of pro-apoptotic BH3-only proteins, activating BAX and BAK at the mitochondria. Here we provide evidence indicating that the full resistance of BAX and BAK double deficient (DKO) cells to ER stress is reverted by stimulation in combination with mild serum withdrawal. Cell death under these conditions was characterized by the appearance of classical apoptosis markers, caspase-9 activation, release of cytochrome c, and was inhibited by knocking down caspase-9, but insensitive to BCL-XL overexpression. Similarly, the resistance of BIM and PUMA double deficient cells to ER stress was reverted by mild serum withdrawal. Surprisingly, BAX/BAK-independent cell death did not require Cyclophilin D (CypD) expression, an important regulator of the mitochondrial permeability transition pore. Our results suggest the existence of an alternative intrinsic apoptosis pathway emerging from a cross talk between the ER and the mitochondria

Anti-neoplastic drugs increase caveolin-1-dependent migration, invasion and metastasis of cancer cells

Indexación: Scopus.Expression of the scaffolding protein Caveolin-1 (CAV1) enhances migration and invasion of metastatic cancer cells. Yet, CAV1 also functions as a tumor suppressor in early stages of cancer, where expression is suppressed by epigenetic mechanisms. Thus, we sought to identify stimuli/mechanisms that revert epigenetic CAV1 silencing in cancer cells and evaluate how this affects their metastatic potential. We reasoned that restricted tissue availability of anti-neoplastic drugs during chemotherapy might expose cancer cells to sub-therapeutic concentrations, which activate signaling pathways and the expression of CAV1 to favor the acquisition of more aggressive traits. Here, we used in vitro [2D, invasion] and in vivo (metastasis) assays, as well as genetic and biochemical approaches to address this question. Colon and breast cancer cells were identified where CAV1 levels were low due to epigenetic suppression and could be reverted by treatment with the methyltransferase inhibitor 5'-azacytidine. Exposure of these cells to anti-neoplastic drugs for short periods of time (24-48 h) increased CAV1 expression through ROS production and MEK/ERK activation. In colon cancer cells, increased CAV1 expression enhanced migration and invasion in vitro via pathways requiring Src-family kinases, as well as Rac-1 activity. Finally, elevated CAV1 expression in colon cancer cells following exposure in vitro to sub-cytotoxic drug concentrations increased their metastatic potential in vivo. Therefore exposure of cancer cells to anti-neoplastic drugs at non-lethal drug concentrations induces signaling events and changes in transcription that favor CAV1-dependent migration, invasion and metastasis. Importantly, this may occur in the absence of selection for drug-resistance.http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=22955&path[]=7243

Genesis and growth of extracellular vesicle-derived microcalcification in atherosclerotic plaques

Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification zones. We also show that calcification morphology and the plaque’s collagen content – two determinants of atherosclerotic plaque stability - are interlinked

Neuronal Assembly Detection and Cell Membership Specification by Principal Component Analysis

In 1949, Donald Hebb postulated that assemblies of synchronously activated neurons are the elementary units of information processing in the brain. Despite being one of the most influential theories in neuroscience, Hebb's cell assembly hypothesis only started to become testable in the past two decades due to technological advances. However, while the technology for the simultaneous recording of large neuronal populations undergoes fast development, there is still a paucity of analytical methods that can properly detect and track the activity of cell assemblies. Here we describe a principal component-based method that is able to (1) identify all cell assemblies present in the neuronal population investigated, (2) determine the number of neurons involved in ensemble activity, (3) specify the precise identity of the neurons pertaining to each cell assembly, and (4) unravel the time course of the individual activity of multiple assemblies. Application of the method to multielectrode recordings of awake and behaving rats revealed that assemblies detected in the cerebral cortex and hippocampus typically contain overlapping neurons. The results indicate that the PCA method presented here is able to properly detect, track and specify neuronal assemblies, irrespective of overlapping membership

HADES RV Programme with HARPS-N at TNG. IV. Time resolved analysis of the Ca II H&K and Hα chromospheric emission of low-activity early-type M dwarfs

Context. M dwarfs are prime targets for current and future planet search programs, particularly those focused on the detection and characterization of rocky planets in the habitable zone. In this context, understanding their magnetic activity is important for two main reasons: it affects our ability to detect small planets and it plays a key role in the characterization of the stellar environment. Aims: We analyze observations of the Ca II H&K and Hα lines as diagnostics of chromospheric activity for low-activity early-type M dwarfs. Methods: We analyze the time series of spectra of 71 early-type M dwarfs collected in the framework of the HADES project for planet search purposes. The HARPS-N spectra simultaneously provide the Ca II H&K doublet and the Hα line. We develop a reduction scheme able to correct the HARPS-N spectra for instrumental and atmospheric effects, and also to provide flux-calibrated spectra in units of flux at the stellar surface. The Ca II H&K and Hα fluxes are then compared with each other, and their time variability is analyzed. Results: We find that the Ca II H and K flux excesses are strongly correlated with each other, while the Hα flux excess is generally less correlated with the Ca II H&K doublet. We also find that Hα emission does not increase monotonically with the Ca II H&K line flux, showing some absorption before being filled in by chromospheric emission when Ca II H&K activity increases. Analyzing the time variability of the emission fluxes, we derive a tentative estimate of the rotation period (on the order of a few tens of days) for some of the program stars, and the typical lifetime of chromospheric active regions (on the order of a few stellar rotations). Conclusions: Our results are in good agreement with similar previous studies. In particular, we find evidence that the chromospheres of early-type M dwarfs could be characterized by different filament coverage, affecting the formation mechanism of the Hα line. We also show that chromospheric structure is likely related to spectral type

HADES RV Programme with HARPS-N at TNG . III. Flux-flux and activity-rotation relationships of early-M dwarfs

Context. Understanding stellar activity in M dwarfs is crucial for the physics of stellar atmospheres and for ongoing radial velocity exoplanet programmes. Despite the increasing interest in M dwarfs, our knowledge of the chromospheres of these stars is far from being complete. Aims: We test whether the relations between activity, rotation, and stellar parameters and flux-flux relationships previously investigated for main-sequence FGK stars and for pre-main-sequence M stars also hold for early-M dwarfs on the main-sequence. Although several attempts have been made so far, here we analyse a large sample of stars undergoing relatively low activity. Methods: We analyse in a homogeneous and coherent way a well-defined sample of 71 late-K/early-M dwarfs that are currently being observed in the framework of the HArps-N red Dwarf Exoplanet Survey (HADES). Rotational velocities are derived using the cross-correlation technique, while emission flux excesses in the Ca II H & K and Balmer lines from Hα up to H∊ are obtained by using the spectral subtraction technique. The relationships between the emission excesses and the stellar parameters (projected rotational velocity, effective temperature, kinematics, and age) are studied. Relations between pairs of fluxes of different chromospheric lines (flux-flux relationships) are also studied and compared with the literature results for other samples of stars. Results: We find that the strength of the chromospheric emission in the Ca II H & K and Balmer lines is roughly constant for stars in the M0-M3 spectral range. Although our sample is likely to be biased towards inactive stars, our data suggest that a moderate but significant correlation between activity and rotation might be present, as well as a hint of kinematically selected young stars showing higher levels of emission in the calcium line and in most of the Balmer lines. We find our sample of M dwarfs to be complementary in terms of chromospheric and X-ray fluxes with those of the literature, extending the analysis of the flux-flux relationships to the very low flux domain. Conclusions: Our results agree with previous works suggesting that the activity-rotation-age relationship known to hold for solar-type stars also applies to early-M dwarfs. We also confirm previous findings that the field stars which deviate from the bulk of the empirical flux-flux relationships show evidence of youth. Based on observations made with the Italian Telescopio Nazionale Galileo (TNG), operated on the island of La Palma by the Fundación Galileo Galilei of the INAF (Istituto Nazionale di Astrofisica) at the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias

Locus for severity implicates CNS resilience in progression of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and is a common cause of chronic neurological disability in young adults(1,2). Here, to provide insight into the potential mechanisms involved in progression, we conducted a genome-wide association study of the age-related MS severity score in 12,584 cases and replicated our findings in a further 9,805 cases. We identified a significant association with rs10191329 in the DYSF-ZNF638 locus, the risk allele of which is associated with a shortening in the median time to requiring a walking aid of a median of 3.7 years in homozygous carriers and with increased brainstem and cortical pathology in brain tissue. We also identified suggestive association with rs149097173 in the DNM3-PIGC locus and significant heritability enrichment in CNS tissues. Mendelian randomization analyses suggested a potential protective role for higher educational attainment. In contrast to immune-driven susceptibility(3), these findings suggest a key role for CNS resilience and potentially neurocognitive reserve in determining outcome in MS