sFlt-1/PIGF no Diagnóstico Preditivo de Pré-eclâmpsia: Estudo de Impacto Económico em Portugal

Overview and Aims: The last decade brought relevant insights into the pathophysiology of preeclampsia (PE), namely the role of the circulating levels of placental growth factor (PlGF) and soluble Fms-like tyrosine kinase-1 (sFlt-1). The purpose of this study is to estimate the financial impact of introducing the sFlt-1/PlGF ratio for the evaluation of women with suspicion of PE in the Portuguese National Healthcare System (SNS). Study Design: budget impact study evaluating short-term costs associated with the introduction of the sFlt-1/PlGF ratio from the SNS payer’s perspective. The time horizon for the study is 1 year. Population: The target population consists of women presenting to the healthcare system with signs or symptoms su ggestive of preeclampsia (estimated in 8500 subjects). Methods: A decision-tree model was used to estimate the budget impact of the introduction of the sFlt-1/PlGF ratio in the SNS. The model compares the management costs in the current clinical practice (“no test” scenario) vs. current diagnostic procedures plus the sFlt-1/PlGF ratio (“test” scenario). Clinical inputs have been derived primarily from literature review and, where data was unavailable, expert opinion. Resources and unit costs have been obtained from Portugal-specific sources. Results: In the current standard practice (no test), total costs were estimated to be €9 863 264 (€1160 per patient), with unnecessary admissions representing about €3,5 million. Total costs in the test scenario sum up to €9 781 194 (€1150 per patient), representing a cost saving to the system of €82 070 (€10 per patient), mainly due to a reduction of false positives and related unnecessary hospitalizations of women not developing PE. Conclusions: There is favorable economic evidence about the introduction of the sFlt- 1/PlGF ratio in the SNS. The generated savings appear to offset the costs related to the test.info:eu-repo/semantics/publishedVersio

Acute kidney injury in pregnancy: a clinical challenge

The incidence of acute kidney injury in pregnancy declined significantly over the second half of the 20th century; however, it is still associated with major maternal and perinatal morbidity and mortality. A set of systemic and renal physiological adaptive mechanisms occur during a normal gestation that will constrain several changes in laboratory parameters of renal function, electrolytes, fluid and acid-base balances. The diagnosis of acute kidney injury in pregnancy is based on the serum creatinine increase. The usual formulas for estimating glomerular filtration rate are not validated in this population. During the first trimester of gestation, acute kidney injury develops most often due to hyperemesis gravidarum or septic abortion. In the third trimester, the differential diagnosis is more challenging for the obstetrician and the nephrologist and comprises some pathologies that are reviewed in this article: preeclampsia/HELLP syndrome, acute fatty liver of pregnancy and thrombotic microangiopathies

Gauge symmetry and W-algebra in higher derivative systems

The problem of gauge symmetry in higher derivative Lagrangian systems is discussed from a Hamiltonian point of view. The number of independent gauge parameters is shown to be in general {\it{less}} than the number of independent primary first class constraints, thereby distinguishing it from conventional first order systems. Different models have been considered as illustrative examples. In particular we show a direct connection between the gauge symmetry and the W-algebra for the rigid relativistic particle.Comment: 1+22 pages, 1 figure, LaTeX, v2; title changed, considerably expanded version with new results, to appear in JHE

Genome-wide signatures of complex introgression and adaptive evolution in the big cats.

The great cats of the genus Panthera comprise a recent radiation whose evolutionary history is poorly understood. Their rapid diversification poses challenges to resolving their phylogeny while offering opportunities to investigate the historical dynamics of adaptive divergence. We report the sequence, de novo assembly, and annotation of the jaguar (Panthera onca) genome, a novel genome sequence for the leopard (Panthera pardus), and comparative analyses encompassing all living Panthera species. Demographic reconstructions indicated that all of these species have experienced variable episodes of population decline during the Pleistocene, ultimately leading to small effective sizes in present-day genomes. We observed pervasive genealogical discordance across Panthera genomes, caused by both incomplete lineage sorting and complex patterns of historical interspecific hybridization. We identified multiple signatures of species-specific positive selection, affecting genes involved in craniofacial and limb development, protein metabolism, hypoxia, reproduction, pigmentation, and sensory perception. There was remarkable concordance in pathways enriched in genomic segments implicated in interspecies introgression and in positive selection, suggesting that these processes were connected. We tested this hypothesis by developing exome capture probes targeting ~19,000 Panthera genes and applying them to 30 wild-caught jaguars. We found at least two genes (DOCK3 and COL4A5, both related to optic nerve development) bearing significant signatures of interspecies introgression and within-species positive selection. These findings indicate that post-speciation admixture has contributed genetic material that facilitated the adaptive evolution of big cat lineages

Heterologous expression screens in Nicotiana benthamiana identify a candidate effector of the wheat Yellow Rust Pathogen that associates with processing bodies

Rust fungal pathogens of wheat (Triticum spp.) affect crop yields worldwide. The molecular mechanisms underlying the virulence of these pathogens remain elusive, due to the limited availability of suitable molecular genetic research tools. Notably, the inability to perform high-throughput analyses of candidate virulence proteins (also known as effectors) impairs progress. We previously established a pipeline for the fast-forward screens of rust fungal candidate effectors in the model plant Nicotiana benthamiana. This pipeline involves selecting candidate effectors in silico and performing cell biology and protein-protein interaction assays in planta to gain insight into the putative functions of candidate effectors. In this study, we used this pipeline to identify and characterize sixteen candidate effectors from the wheat yellow rust fungal pathogen Puccinia striiformis f sp tritici. Nine candidate effectors targeted a specific plant subcellular compartment or protein complex, providing valuable information on their putative functions in plant cells. One candidate effector, PST02549, accumulated in processing bodies (P-bodies), protein complexes involved in mRNA decapping, degradation, and storage. PST02549 also associates with the P-body-resident ENHANCER OF mRNA DECAPPING PROTEIN 4 (EDC4) from N. benthamiana and wheat. We propose that P-bodies are a novel plant cell compartment targeted by pathogen effectors

Illiteracy, low educational status, and cardiovascular mortality in India

Background: Influence of education, a marker of SES, on cardiovascular disease (CVD) mortality has not been evaluated in low-income countries. To determine influence of education on CVD mortality a cohort study was performed in India. Methods: 148,173 individuals aged ≥ 35 years were recruited in Mumbai during 1991-1997 and followed to ascertain vital status during 1997-2003. Subjects were divided according to educational status into one of the five groups: illiterate, primary school ( ≦ 5 years of formal education), middle school (6-8 years), secondary school (9-10 years) and college (> 10 years). Multivariate analyses using Cox proportional hazard model was performed an

Behavior and Impact of Zirconium in the Soil–Plant System: Plant Uptake and Phytotoxicity

Because of the large number of sites they pollute, toxic metals that contaminate terrestrial ecosystems are increasingly of environmental and sanitary concern (Uzu et al. 2010, 2011; Shahid et al. 2011a, b, 2012a). Among such metals is zirconium (Zr), which has the atomic number 40 and is a transition metal that resembles titanium in physical and chemical properties (Zaccone et al. 2008). Zr is widely used in many chemical industry processes and in nuclear reactors (Sandoval et al. 2011; Kamal et al. 2011), owing to its useful properties like hardness, corrosion-resistance and permeable to neutrons (Mushtaq 2012). Hence, the recent increased use of Zr by industry, and the occurrence of the Chernobyl and Fukashima catastrophe have enhanced environmental levels in soil and waters (Yirchenko and Agapkina 1993; Mosulishvili et al. 1994 ; Kruglov et al. 1996)

Where form and substance meet: using the narrative approach of re-storying to generate research findings and community rapprochement in (university) mathematics education

Storytelling is an engaging way through which lived experience can be shared and reflected upon, and a tool through which difference, diversity—and even conflict—can be acknowledged and elaborated upon. Narrative approaches to research bring the richness and vibrancy of storytelling into how data is collected and interpretations of it shared. In this paper, I demonstrate the potency of the narrative approach of re-storying for a certain type of university mathematics education research (non-deficit, non-prescriptive, context-specific, example-centred and mathematically focused) conducted at the interface of two communities: mathematics education and mathematics. I do so through reference to Amongst Mathematicians (Nardi, 2008), a study carried out in collaboration with 20 university mathematicians from six UK mathematics departments. The study deployed re-storying to present data and analyses in the form of a dialogue between two fictional, yet entirely data-grounded, characters—M, mathematician, and RME, researcher in mathematics education. In the dialogues, the typically conflicting epistemologies—and mutual perceptions of such epistemologies—of the two communities come to the fore as do the feasibility-of, benefits-from, obstacles-in and conditions-for collaboration between these communities. First, I outline the use of narrative approaches in mathematics education research. Then, I introduce the study and its use of re-storying, illustrating this with an example: the construction of a dialogue from interview data in which the participating mathematicians discuss the potentialities and pitfalls of visualisation in university mathematics teaching. I conclude by outlining re-storying as a vehicle for community rapprochement achieved through generating and sharing research findings—the substance of research—in forms that reflect the fundamental principles and aims that underpin this research. My conclusions resonate with sociocultural constructs that view mathematics teacher education as contemporary praxis and the aforementioned inter-community discussion as taking place within a third space

SREBP-2/PNPLA8 axis improves non-alcoholic fatty liver disease through activation of autophagy

Dysregulated autophagy is associated with steatosis and non-alcoholic fatty liver disease (NAFLD), however the mechanisms connecting them remain poorly understand. Here, we show that co-administration of lovastatin and ezetimibe (L/E) significantly reverses hepatic triglyceride accumulation concomitant with an increase in SREBP-2 driven autophagy in mice fed a high-fat diet (HFD). We further show that the statin mediated increase in SREBP-2 directly activates expression of patatin-like phospholipase domain-containing enzyme 8 (PNPLA8) gene, and PNPLA8 associates with autophagosomes and is associated with a decrease in cellular triglyceride. Moreover, we show that over-expression of PNPLA8 dramatically decreases hepatic steatosis through increased autophagy in hepatocytes of HFD-fed mice. Live-cell imaging analyses also reveal that PNPLA8 dynamically interacts with LC3 and we suggest that the SREBP-2/PNPLA8 axis represents a novel regulatory mechanism for lipid homeostasis. These data provide a possible mechanism for the reported beneficial effects of statins for decreasing hepatic triglyceride levels in NAFLD patients.ope