Changes in MicroRNA Expression during Rabbit Hemorrhagic Disease Virus (RHDV) Infection.

Current knowledge on the role of microRNAs (miRNAs) in rabbit hemorrhagic disease virus (RHDV) infection and the pathogenesis of rabbit hemorrhagic disease (RHD) is still limited. RHDV replicates in the liver, causing hepatic necrosis and liver failure. MiRNAs are a class of short RNA molecules, and their expression profiles vary over the course of diseases, both in the tissue environment and in the bloodstream. This paper evaluates the expression of miRNAs in the liver tissue (ocu-miR-122-5p, ocu-miR-155-5p, and ocu-miR-16b-5p) and serum (ocu-miR-122-5p) of rabbits experimentally infected with RHDV. The expression levels of ocu-miR-122-5p, ocu-miR-155-5p, and ocu-miR-16b-5p in liver tissue were determined using reverse transcription quantitative real-time PCR (RT-qPCR), and the expression level of circulating ocu-miR-122-5p was established using droplet digital PCR (ddPCR). The expression levels of ocu-miR-155-5p and ocu-miR-16b-5p were significantly higher in the infected rabbits compared to the healthy rabbits (a fold-change of 5.8 and 2.5, respectively). The expression of ocu-miR-122-5p was not significantly di�erent in the liver tissue from the infected rabbits compared to the healthy rabbits (p = 0.990), while the absolute expression level of the circulating ocu-miR-122-5p was significantly higher in the infected rabbits than in the healthy rabbits (p < 0.0001). Furthermore, a functional analysis showed that ocu-miR-155-5p, ocu-miR-16b-5p, and ocu-miR-122-5p can regulate the expression of genes involved in processes correlated with acute liver failure (ALF) in rabbits. Search tool for the retrieval of interacting genes/proteins (STRING) analysis showed that the potential target genes of the three selected miRNAs may interact with each other in di�erent pathways. The results indicate the roles of these miRNAs in RHDV infection and over the course of RHD and may reflect hepatic inflammation and impairment/dysfunction in RHD

Hereditary xerocytosis - spectrum and clinical manifestations of variants in the PIEZO1 gene, including co-occurrence with a novel β-globin mutation

Hereditary xerocytosis (HX) is a rare, autosomal dominant congenital hemolytic anemia (CHA) characterized by erythrocyte dehydration with presentation of various degrees of hemolytic anemia. HX is often misdiagnosed as hereditary spherocytosis or other CHA. Here we report three cases of suspected HX and one case of HX associated with β-thalassemia. Sanger method was used for sequencing cDNA of the PIEZO1 gene. Variants were evaluated for potential pathogenicity by MutationTaster, PROVEAN, PolyPhen-2 and M-CAP software, and by molecular modeling. Four different variants in the PIEZO1 gene were found, including three substitutions (p.D669H, p.D1566G, p.T1732 M) and one deletion (p.745delQ). In addition, in the patient with the p.T1732 M variant we detected a 12-nucleotide deletion in the β-globin gene leading to a deletion of amino acids 62AHGK65. The joint presence of mutations in two different genes connected with erythrocytes markedly aggravated the presentation of the disease. Bioinformatic analysis and molecular modeling strongly indicated likely deleterious effects of all four PIEZO1 variants, but co-segregation analysis showed that the p.D1566G substitution is in fact non-pathogenic. Identification of causative mutations should improve the diagnosis and management of HX and provide a new insight into the molecular basis of this complex red blood cell abnormality

Serum microRNA in patients undergoing atrial fibrillation ablation.

MicroRNAs mediate posttranscriptional gene regulation. The aim of the study was to find a microRNA predictor of successful atrial fibrillation (AF) ablation. A total of 109 patients undergoing first-time AF ablation were included. Nineteen patients were selected to undergo serum microRNA sequencing (study group). The sequencing data were used to select several microRNAs that correlated with 12-month recurrences after AF ablation. Those microRNAs were validated by digital droplet PCR in samples from remaining 90 patients. All patients underwent pulmonary vein isolation (RF ablation, contact force catheter, electroanatomical system). The endpoint of the study was the 12-month AF recurrence rate; the overall recurrence rate was 42.5%. In total, levels of 34 miRNAs were significantly different in sera from patients with AF recurrence compared to patients without AF recurrence. Six microRNAs (miR-183-5p, miR-182-5p, miR-32-5p, miR-107, miR-574-3p, and miR-144-3p) were validated in the whole group. Data from the validation group did not confirm the observations from the study group, as no significant differences were found between miRNAs serum levels in patients with and without recurrences 12 months after AF ablation

A novel microRNA differentially expressed in patients with persistent and paroxysmal atrial fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the general population. The estimated prevalence of this arrhythmia in adults ranges from 2% to 4%.1 AF is one of the leading causes of stroke, heart failure, other thromboembolic complications, and sudden death. On the basis of the duration of an arrhythmia episode, AF is classified as first-diagnosed, paroxysmal, persistent, long-standing persistent, or permanent.2 In recent years, there has been a growing body of evidence that microRNAs (miRNAs) play an important role in AF development and progression.3 Advances in next-generation sequencing technologies made it possible to identify and evaluate putative novel miRNAs associated with this arrhythmia. Hence, the main goal of this study was to identify novel circulating serum miRNAs that can differentiate between paroxysmal and persistent AF, and may serve as potential diagnostic biomarkers

A Family Affected by a Life-Threatening Erythrocyte Defect Caused by Pyruvate Kinase Deficiency With Normal Iron Status: A Case Report

Background: Red cell pyruvate kinase deficiency (PKD) is a defect of glycolysis causing congenital non-spherocytic hemolytic anemia. PKD is transmitted as an autosomal recessive trait. The clinical features of PKD are highly variable, from mild to life-threatening anemia which can lead to death in the neonatal period. Most patients with PKD must receive regular transfusions in early childhood and as a consequence suffer from iron overloading. Patient: Here, we report a Polish family with life-threatening hemolytic anemia of unknown etiology. Whole exome sequencing identified two heterozygous mutations, c.1529 G > A (p.R510Q) and c.1495 T > C (p.S499P) in the PKLR gene. Molecular modeling showed that the both PKLR mutations are responsible for major disturbance of the protein structure and functioning. Despite frequent transfusions the patients do not show any signs of iron overload and hepcidin, a major regulator of iron uptake, is undetectable in their serum. The patients were homozygous for the rs855791 variant of the TMPRSS6 gene which has earlier been shown to down-regulate iron absorption and accumulation. Conclusion: The lack of iron overload despite a reduced level of hepcidin in two transfusion-dependent PKD patients suggests the existence of a hepcidin-independent mechanism of iron regulation preventing iron overloading

Expression of versican mRNA transcript to predict cardiac remodelling after myocardial infarction

Background: Adverse left-ventricular remodelling (LVR) is defined as an increase in end-diastolic left-ventricular volume by 20% 6 months after acute myocardial infarction (AMI). LVR is associated with cardiac dysfunction, therefore deteriorating the prognosis. Aims: We aimed to compare the concentrations of messenger RNA transcripts in the peripheral blood of patients with and without LVR at 6 months. Methods: The study included 75 patients with first ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention. Whole blood concentrations of 6 transcripts were determined 24 hours after AMI using droplet digital polymerase chain reaction. The correlations between mRNA transcript expression and left ventricular ejection fraction (LVEF) and N-terminal-pro B type natriuretic peptide (NT-proBNP) concentration were evaluated. Results: Among 75 patients, 4 were lost to follow-up and 71 were included in the analysis. Seventeen (24%) patients developed LVR at 6 months. Versican (VCAN) mRNA expression was lower in patients who developed LVR, compared to those who did not (P = 0.02), and discriminated between these patients (area under the ROC curve 67%; P = 0.04). Expression of VCAN transcript < 75.3 normalized units predicted LVR with 71% sensitivity and 67% specificity. In a multivariable regression analysis, VCAN expression remained the only independent predictor of LVR (OR 3.475; 95% CI, 1.000-12.075; P = 0.04). Conclusions: Dysregulation of VCAN expression in the acute phase of AMI may contribute to LVR at 6 months. Whether decreased expression of VCAN might be a useful tool to predict LVR in clinical practice remains to be established

System design for social intervention : improving throuhg interior design the client’s experience and staff productivity

Santa Casa de Misericordia is an organization, whose mission is to treat and support the sick and disabled, as well as assist “exposed ones”. Principally, it is recognizable by its social services. Big matters of society are social exclusion, loneliness, managing unemployment, etc. At some point of our lives we will all need some kind of level of care. By intervention is destined any program, service, policy, or product that is intended to eventually influence or change people´s social, environmental, and organizational conditions as well as their choices, attitudes, beliefs, and behaviors. Social care interventions tend to be compound, programmatic and dependent. They occur through investigation and analysis and discovering solutions at the end. To achieve this, there is a need to select, adapt and evaluate given information and apply it to present environment. This dissertation aims to create physical surroundings that are “psychologically supportive”, where a significant relationship exists between a client and organization. Different features are studied, in order to achieve a matching solution and interior design guides to create a specific type of space. There is scientific evidence, that poor design works in contradiction of the well being of clients of social services, also its employees. The second part of this study is based on existing facility located in Rua das Janelas Verdes. It is a base for project, helping to understand the space and relationships occurring there. I have used methods of Evidance Based Design and a questionnaire to collect primary data. By changing the interior design of this facility, it was intended to improve mostly patient´s experience with Santa Casa de Misericordia, but also the employees. Improving facilities image may help clients enjoy better the service and help the employees cope better with workplace stress and to provide a better service, while outcomes will rise. Current design and floor plans were investigated and studied. Its exploration, observation and analysis led me to significant solutions and conclusions. Environmental factors do have an influence, on how service is perceived but its clients. Not only clients, but also employees are always a part of it. Interior and exterior surroundings have impact on all human beings. Textures, lights, nature and art have individual responses and the majority of respondeds believed that the social care environment had a direct influence on well-being, productivity and coping with stres

The combined impact of mechanical factors on the wall stress of the human ascending aorta – a finite elements study

Abstract Background Biomechanical factors influence stress in the aortic wall. The aim of this study was to assess how the diameter and shape of the vessel, blood pressure and longitudinal systolic aortic stretching (SAS) caused by the contraction of the myocardium influence stress in the aortic wall. Methods Three computational models of the non-dilated aorta and aneurysms of the ascending aorta and aortic root were created. Then, finite elements analyses were carried out. The models were subjected to blood pressure (120 mmHg and 160 mmHg) and longitudinal systolic aortic stretching (0 mm, 5 mm, 10 mm and 15 mm). The influence of wall elasticity was examined too. Results Blood pressure had a smaller impact on the stress than the SAS. An increase in blood pressure from 120 mmHg to 160 mmHg increased the peak wall stress (PWS) on average by 0.1 MPa in all models. A 5 mm SAS caused a 0.1–0.2 MPa increase in PWS in all the models. The increase in PWS caused by a 10 mm and 15 mm SAS was 0.2 MPa and 0.4 MPa in the non-dilated aorta, 0.2–0.3 MPa and 0.3–0.5 MPa in the aneurysm of the ascending aorta, and 0.1–0.2 MPa and 0.2–0.3 MPa in the aortic root aneurysm model, respectively. The loss of elasticity of the aneurysmal wall resulted in an increase of PWS by 0.1–0.2 MPa. Conclusions Aortic geometry, wall stiffness, blood pressure and SAS have an impact on PWS. However, SAS had the biggest impact on wall stress. The results of this study may be useful in future patient-specific computational models used to assess the risk of aortic complications

The Dancing Brain: Structural and Functional Signatures of Expert Dance Training

Dance – as a ritual, therapy, and leisure activity – has been known for thousands of years. Today, dance is increasingly used as therapy for cognitive and neurological disorders such as dementia and Parkinson’s disease. Surprisingly, the effects of dance training on the healthy young brain are not well understood despite the necessity of such information for planning successful clinical interventions. Therefore, this study examined actively performing, expert-level trained college students as a model of long-term exposure to dance training. To study the long-term effects of dance training on the human brain, we compared 20 young expert female Dancers with normal body mass index with 20 age- and education-matched Non-Dancers with respect to brain structure and function. We used diffusion tensor, morphometric, resting state and task-related functional MRI, a broad cognitive assessment, and objective measures of selected dance skill (Dance Central video game and a balance task). Dancers showed superior performance in the Dance Central video game and balance task, but showed no differences in cognitive abilities. We found little evidence for training-related differences in brain volume in Dancers. Dancers had lower anisotropy in the corticospinal tract. They also activated the action observation network (AON) to greater extent than Non-Dancers when viewing dance sequences. Dancers showed altered functional connectivity of the AON, and of the general motor learning network. These functional connectivity differences were related to dance skill and balance and training-induced structural characteristics. Our findings have the potential to inform future study designs aiming to monitor dance training-induced plasticity in clinical populations