Risk factors for paravalvular leak after transcatheter aortic valve replacement

Objective. To assess risk factors for paravalvular leak (PVL) after transcatheter aortic valve implantation (TAVI) in a large single-center cohort, including measurement of aortic valve calcification using a reproducible method. Methods. We retrospectively analyzed preoperative contrast-enhanced multidetector computed tomography (MDCT) scans of patients who underwent TAVI in our center between 2009 and 2016. Calcium volume was calculated for each aortic cusp in the aortic valve (AV), left ventricular outflow tract (LVOT) and device-landing zone (DLZ). Results. Overall, 539 patients were included in the study (Edwards SapienXT, n=192; Edwards Sapien3, n=206; Medtronic CoreValve EvolutR, n=44; Symetis Acurate, n=97). Median calcium volume in the DLZ was 757 mm3, with no significant differences among the four prosthesis groups. None of the patients had severe PVL. The overall incidence of mild-to-moderate PVL was 15.8% (95% CI: 12.8-19.1%). On multivariate logistic regression, DLZ calcification (p=0.00006; OR for an increase of 100 mm3 1.08; 95% CI: 1.04-1.13) and use of the CoreValve (p=0.0028; OR 4.1; 95% CI: 1.6-10 with SapienXT as reference) prosthesis were found to be associated with ≥mild PVL. In contrast, degree of oversizing (p=0.002; OR 0.97; 95% CI: 0.95-0.99), and use of Sapien3 (p=0.00005; OR 0.23; 95% CI: 0.11-0.47 with SapienXT as reference) were associated with a lower incidence of ≥mild PVL. Conclusions. Aortic calcification volume in the DLZ is associated with residual PVL after TAVI. When taking calcification into account, the balloon-expandable prosthesis Sapien3 seems to be associated with a lower incidence of PVL

Dissecting the molecular mechanisms of breast cancer bone metastasis for therapeutic targeting

Breast cancer that has metastasized to bone is currently an incurable disease, causing significant morbidity and mortality. The aim of this thesis work was to elucidate molecular mechanisms of bone metastasis and thereby gain insights into novel therapeutic approaches. First, we found that L‐serine biosynthesis genes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1) and phosphoserine phosphatase (PSPH), were up‐regulated in highly bone metastatic MDA‐MB‐231(SA) cells as compared with the parental breast cancer cell line. Knockdown of serine biosynthesis inhibited proliferation of MDA‐MB‐231(SA) cells, and L‐serine was essential for the formation of bone resorbing osteoclasts. Clinical data demonstrated that high expression of PHGDH and PSAT1 was associated with decreased relapse‐free and overall survival and with features typical of poor outcome in breast cancer. Second, RNA interference screening pointed out heparan sulfate 6‐O‐sulfotransferase 2 (HS6ST2) as a critical gene for transforming growth factor β (TGF‐β)‐induced interleukin 11 (IL‐11) production in MDA‐MB‐231(SA) cells. Exogenous heparan sulfate glycosaminoglycans heparin and K5‐NSOS also inhibited TGF‐β‐induced IL‐11 production in MDA‐MB‐231(SA) cells. Furthermore, K5‐NSOS decreased osteolytic lesion area and tumor burden in bone in mice. Third, we discovered that the microRNAs miR‐204, ‐211 and ‐379 inhibited IL‐11 expression in MDA‐MB‐231(SA) cells through direct targeting of the IL‐11 mRNA. MiR‐379 also inhibited Smad‐mediated signaling. Gene expression profiling of miR‐204 and ‐379 transfected cells indicated that these microRNAs down‐regulate several bone metastasis‐relevant genes, including prostaglandin‐endoperoxide synthase 2 (PTGS2). Taken together, this study identified three potential treatment strategies for bone metastatic breast cancer: inhibition of serine biosynthesis, heparan sulfate glycosaminoglycans and restoration of miR‐204/‐211/‐379.Siirretty Doriast

Cyanobacterial Acclimation to Changing Environmental Conditions - Roles for Group 2 Sigma Factors in Synechocystis sp. PCC 6803

Siirretty Doriast

Daunting, reliable, important or “trivial nitpicking?” Upper secondary students’ expectations and experiences of the English test in the Matriculation Examination

The Matriculation Examination, the school-leaving exam taken towards the end of upper secondary education, is the only high-stakes examination in the Finnish school system. As the exam may have a strong impact on the students’ further education opportunities, it evokes various feelings and thoughts in students. Yet, there is little research on these reactions. This article, based on a mixed-methods approach, sheds light on students’ expectation and experiences of the English test in the Matriculation Examination. A total of 142 second- and third-year students from one upper secondary school shared their views on the possible washback effect and test anxiety caused by the exam. Also, the students expressed their ideas and experiences of the validity, reliability and fairness of the test. Although the test did not seem to cause excessive washback, it caused significant stress and anxiety. Furthermore, students seemed rather critical of its validity and reliability

Beyond error correction in EFL writing in a Finnish upper secondary classroom: a practical approach

In Finland, teachers have considerable autonomy over their assessment practices. Recent studies suggest that FL/L2 teachers, particularly at the upper secondary school, primarily focus on summative assessment rather than on formative assessment and feedback, which is in contrast with the latest Finnish National Core Curricula. Furthermore, while appreciating teacher feedback, learners do not perceive it as an integral part of assessment. In this paper, we propose formative classroom practices to support the learning process and go beyond error correction in FL/L2 writing. These practices are grounded on our earlier research, and they focus mainly on two themes: fostering learner choice in feedback and error correction methodology, and supporting peer feedback with the help of a checklist based on the Matriculation Examination rating scale. Drawing from students’ comments and texts, we will explore learner experiences with these assessment practices and the changes they may bring to the classroom.In Finland, teachers have considerable autonomy over their assessment practices. Recent studies suggest that FL/L2 teachers, particularly at the upper secondary school, primarily focus on summative assessment rather than on formative assessment and feedback, which is in contrast with the latest Finnish National Core Curricula. Furthermore, while appreciating teacher feedback, learners do not perceive it as an integral part of assessment. In this paper, we propose formative classroom practices to support the learning process and go beyond error correction in FL/L2 writing. These practices are grounded on our earlier research, and they focus mainly on two themes: fostering learner choice in feedback and error correction methodology and supporting peer feedback with the help of a checklist based on the Matriculation Examination rating scale. Drawing from students’ comments and texts, we will explore learner experiences with these assessment practices and the changes they may bring to the classroom

Using Stata for questionnaire development

In studies which collect survey data, the investigator(s) often construct the questionnaire using a word processor and then deliver it to a survey organization which translates it into an electronic data collection instrument (e.g., CAPI or CATI). Unfortunately, this approach suffers from the following problems: (1) a word processor is not well-suited to the development of a complex questionnaire, (2) time is wasted and errors may occur when translating the questionnaire into CAPI, and (3) background information about the individual questions which is often relevant for analysis of the data (e.g., question source and rationale, scoring instructions, etc.) is not preserved in the final data file. We shall describe a system we are developing which permits an investigator to construct a questionnaire in Stata by representing questions as variables and using labels and characteristics to specify attributes such as question text, response categories, and background information together with specifications regarding the structure of the interview (e.g., skip patterns and loops). The resulting .dta file is then automatically translated into a variety of useful forms, including a human-readable version of the questionnaire and a format that may be imported directly into CAPI. The file also serves as a shell into which the actual data may be placed so that researchers analyzing the data have easy access to question attributes.

Plant RNA Regulatory Network and RNA Granules in Virus Infection

Regulation of post-transcriptional gene expression on mRNA level in eukaryotic cells includes translocation, translation, translational repression, storage, mRNA decay, RNA silencing, and nonsense-mediated decay. These processes are associated with various RNA-binding proteins and cytoplasmic ribonucleoprotein complexes many of which are conserved across eukaryotes. Microscopically visible aggregations formed by ribonucleoprotein complexes are termed RNA granules. Stress granules where the translationally inactive mRNAs are stored and processing bodies where mRNA decay may occur present the most studied RNA granule types. Diverse RNP-granules are increasingly being assigned important roles in viral infections. Although the majority of the molecular level studies on the role of RNA granules in viral translation and replication have been conducted in mammalian systems, some studies link also plant virus infection to RNA granules. An increasing body of evidence indicates that plant viruses require components of stress granules and processing bodies for their replication and translation, but how extensively the cellular mRNA regulatory network is utilized by plant viruses has remained largely enigmatic. Antiviral RNA silencing, which is an important regulator of viral RNA stability and expression in plants, is commonly counteracted by viral suppressors of RNA silencing. Some of the RNA silencing suppressors localize to cellular RNA granules and have been proposed to carry out their suppression functions there. Moreover, plant nucleotide-binding leucine-rich repeat protein-mediated virus resistance has been linked to enhanced processing body formation and translational repression of viral RNA. Many interesting questions relate to how the pathways of antiviral RNA silencing leading to viral RNA degradation and/or repression of translation, suppression of RNA silencing and viral RNA translation converge in plants and how different RNA granules and their individual components contribute to these processes. In this review we discuss the roles of cellular RNA regulatory mechanisms and RNA granules in plant virus infection in the light of current knowledge and compare the findings to those made in animal virus studies.Peer reviewe

Axial Optical Traps: A New Direction for Optical Tweezers

AbstractOptical tweezers have revolutionized our understanding of the microscopic world. Axial optical tweezers, which apply force to a surface-tethered molecule by directly moving either the trap or the stage along the laser beam axis, offer several potential benefits when studying a range of novel biophysical phenomena. This geometry, although it is conceptually straightforward, suffers from aberrations that result in variation of the trap stiffness when the distance between the microscope coverslip and the trap focus is being changed. Many standard techniques, such as back-focal-plane interferometry, are difficult to employ in this geometry due to back-scattered light between the bead and the coverslip, whereas the noise inherent in a surface-tethered assay can severely limit the resolution of an experiment. Because of these complications, precision force spectroscopy measurements have adapted alternative geometries such as the highly successful dumbbell traps. In recent years, however, most of the difficulties inherent in constructing a precision axial optical tweezers have been solved. This review article aims to inform the reader about recent progress in axial optical trapping, as well as the potential for these devices to perform innovative biophysical measurements

In Teachers We Trust – the Finnish Way to Teach and Learn

Finland has received very good results in international student achievement tests such as PISA and ICCS in the 21st century. Consequently, education authorities and researchers from all over the world have attempted to find reasons for Finland’s success. In this article, we are looking at Finnish education from the inside, from the perspective of Finnish teachers and schools. Our hypothesis is that Finnish teachers, who have a high-quality academic education and who work as trusted professionals, have played a key role in making such results possible. Thus, we will concentrate on Finnish teachers, their role in education as well as teacher education and training in this article