RNA sequencing of chorionic villi from recurrent pregnancy loss patients reveals impaired function of basic nuclear and cellular machinery

Recurrent pregnancy loss (RPL) concerns similar to 3% of couples aiming at childbirth. In the current study, transcriptomes and miRNomes of 1st trimester placental chorionic villi were analysed for 2 RPL cases (>= 6 miscarriages) and normal, but electively terminated pregnancies (ETP; n = 8). Sequencing was performed on Illumina HiSeq 2000 platform. Differential expression analyses detected 51 (27%) transcripts with increased and 138 (73%) with decreased expression in RPL compared to ETP (DESeq: FDR P <0.1 and DESeq2: <0.05). RPL samples had substantially decreased transcript levels of histones, regulatory RNAs and genes involved in telomere, spliceosome, ribosomal, mitochondrial and intra-cellular signalling functions. Downregulated expression of HIST1H1B and HIST1H4A (Wilcoxon test, fcPeer reviewe

Extensive shift in placental transcriptome profile in preeclampsia and placental origin of adverse pregnancy outcomes

One in five pregnant women suffer from gestational complications, prevalently driven by placental malfunction. Using RNASeq, we analyzed differential placental gene expression in cases of normal gestation, late-onset preeclampsia (LO-PE), gestational diabetes (GD) and pregnancies ending with the birth of small-for-gestational-age (SGA) or large-for-gestational-age (LGA) newborns (n = 8/group). In all groups, the highest expression was detected for small noncoding RNAs and genes specifically implicated in placental function and hormonal regulation. The transcriptome of LO-PE placentas was clearly distinct, showing statistically significant (after FDR) expressional disturbances for hundreds of genes. Taqman RT-qPCR validation of 45 genes in an extended sample (n = 24/group) provided concordant results. A limited number of transcription factors including LRF, SP1 and AP2 were identified as possible drivers of these changes. Notable differences were detected in differential expression signatures of LO-PE subtypes defined by the presence or absence of intrauterine growth restriction (IUGR). LO-PE with IUGR showed higher correlation with SGA and LO-PE without IUGR with LGA placentas. Whereas changes in placental transcriptome in SGA, LGA and GD cases were less prominent, the overall profiles of expressional disturbances overlapped among pregnancy complications providing support to shared placental responses. The dataset represent a rich catalogue for potential biomarkers and therapeutic targets.Peer reviewe

Infographic consensus recommendations on the classification, definition and diagnostic criteria of hip-related pain in young and middle-aged active adults from the International Hip-related Pain Research Network, Zurich 2018

**Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliate “Michael Drew" is provided in this record*

Mapping memory binding onto the connectome's temporal dynamics:toward a combined biomarker for Alzheimer's disease

En este trabajo proponemos que tras la caída de la hipótesis de cascada amiloide en al enfermedad del Alzheimer (EA), la conectividad cerebral distribuida (que va más allá de regiones clásicamente asociadas a AD, como el hipocampo) y que se extiende a regiones parietales podría representar una nueva línea de investigación. Más aun, la combinación de la conectividad de redes espontaneas junto con las respuestas cerebrales durante tareas de memoria de integración podría permitir identificar y caracterizar las etapas preclínicas de la EA.Fil: Ibáñez Barassi, Agustín Mariano. Instituto de Neurología Cognitiva. Laboratorio de Psicología Experimental y Neurociencia; Argentina. Universidad Diego Portales; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Parra, Mario A.. University of Edinburgh; Reino Unido. Scottish Dementia Clinical Research Network. Alzheimer Scotland Dementia Research Centre; Reino Unid

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): And randomised, phase 3, open-label, multicentre study

Background: Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods: In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m2 on days 1 and 2 of cycle 1; 56 mg/m2 thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m2; intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. Findings: Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11·9 months (IQR 9·3-16·1) in the carfilzomib group and 11·1 months (8·2-14·3) in the bortezomib group. Median progression-free survival was 18·7 months (95% CI 15·6-not estimable) in the carfilzomib group versus 9·4 months (8·4-10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53 [95% CI 0·44-0·65]; p<0·0001). On-study death due to adverse events occurred in 18 (4%) of 464 patients in the carfilzomib group and in 16 (3%) of 465 patients in the bortezomib group. Serious adverse events were reported in 224 (48%) of 463 patients in the carfilzomib group and in 162 (36%) of 456 patients in the bortezomib group. The most frequent grade 3 or higher adverse events were anaemia (67 [14%] of 463 patients in the carfilzomib group vs 45 [10%] of 456 patients in the bortezomib group), hypertension (41 [9%] vs 12 [3%]), thrombocytopenia (39 [8%] vs 43 [9%]), and pneumonia (32 [7%] vs 36 [8%]). Interpretation: For patients with relapsed or refractory multiple myeloma, carfilzomib with dexamethasone could be considered in cases in which bortezomib with dexamethasone is a potential treatment option. Funding: Onyx Pharmaceuticals, Inc., an Amgen subsidiary

Patient-reported outcome measures for hip-related pain: A review of the available evidence and a consensus statement from the International Hip-related Pain Research Network, Zurich 2018

Hip-related pain is a well-recognised complaint among active young and middle-aged active adults. People experiencing hip-related disorders commonly report pain and reduced functional capacity, including difficulties in executing activities of daily living. Patient-reported outcome measures (PROMs) are essential to accurately examine and compare the effects of different treatments on disability in those with hip pain. In November 2018, 38 researchers and clinicians working in the field of hip-related pain met in Zurich, Switzerland for the first International Hip-related Pain Research Network meeting. Prior to the meeting, evidence summaries were developed relating to four prioritised themes. This paper discusses the available evidence and consensus process from which recommendations were made regarding the appropriate use of PROMs to assess disability in young and middle-aged active adults with hip-related pain. Our process to gain consensus had five steps: (1) systematic review of systematic reviews; (2) preliminary discussion within the working group; (3) update of the more recent high-quality systematic review and examination of the psychometric properties of PROMs according to established guidelines; (4) formulation of the recommendations considering the limitations of the PROMs derived from the examination of their quality; and (5

RNA kvaliteedi mõju transkriptoomi sekveneerimise tulemustele

2018-05-2

Notas respecto a la investigación histórica reciente en América del Sur: el caso de Chile

Describimos brevemente aspectos importantes de la historiografía convencional chilena y su continuidad temática, las nuevas contribuciones en el ámbito de la historia política y enunciamos algunos de los temas emergentes de investigación histórica existentes en nuestro medio. Se proporcionarán algunas ideas relacionadas con diversos problemas históricos y algunas de sus correspondientes fuentes mediante las cuales sea posible abordarlos, desde una perspectiva histórica actual. En primer lugar, se tratará los aspectos tradicionales de la historiografía mientras que en segundo los concernientes a la ¿Nueva Historia¿. Además, por cada una de las temáticas abordadas por la historiografía, indicaremos una diversidad de estudios realizados, lo cual servirá para que el lector pueda tener un marco general acerca de las diferentes áreas de estudio e investigación, ilustrando mejor nuestra exposición. Finalmente, presentamos algunas conclusiones con respecto al estudio realizado

Notas respecto a la investigación histórica reciente en América del Sur: el caso de Chile

<p><span class="blk9">Describimos brevemente aspectos importantes de la historiografía convencional chilena y su continuidad temática, las nuevas contribuciones en el ámbito de la historia política y enunciamos algunos de los temas emergentes de investigación histórica existentes en nuestro medio. Se proporcionarán algunas ideas relacionadas con diversos problemas históricos y algunas de sus correspondientes fuentes mediante las cuales sea posible abordarlos, desde una perspectiva histórica actual. En primer lugar, se tratará los aspectos tradicionales de la historiografía mientras que en segundo los concernientes a la “Nueva Historia”. Además, por cada una de las temáticas abordadas por la historiografía, indicaremos una diversidad de estudios realizados, lo cual servirá para que el lector pueda tener un marco general acerca de las diferentes áreas de estudio e investigación, ilustrando mejor nuestra exposición. Finalmente, presentamos algunas conclusiones con respecto al estudio realizado.</span></p><p><span class="blk9">___________________</span></p><p><span class="blk9"><strong>ABSTRACT:</strong></span></p><p><span class="blk9">This article briefly describes important points of the conventional Chilean historiography, its thematic continuity, and the new contributions in the field of politic history; and the same time it presents some of the new emerging subjects in historical investigation. It also provides new ideas related with diverse historical problems, and some of their corresponding sources, through which they could be dealt, always from a contemporary historical perspective. Firstly, it deals with the traditional aspects of historiography, to continue then with those concerning the "New History". In addition, it supplies a list of multiple studies linked to each one of the subjects studied by historiography that will provide the readers a good general view of the different fields of study and investigation, explaining better the present exposition. Finally, it presents some conclusions obtained after this study.<br /></span></p