Holmankjellerup7801

RNA editing is one of the most prevalent and abundant forms of post-transcriptional RNA modification observed in normal physiological processes and often aberrant in diseases including cancer. RNA editing changes the sequences of mRNAs, making them different from the source DNA sequence. Edited mRNAs can produce editing-recoded protein isoforms that are functionally different from the corresponding genome-encoded protein isoforms. The major type of RNA editing in mammals occurs by enzymatic deamination of adenosine to inosine (A-to-I) within double-stranded RNAs (dsRNAs) or hairpins in pre-mRNA transcripts. Enzymes that catalyse these processes belong to the adenosine deaminase acting on RNA (ADAR) family. The vast majority of knowledge on the RNA editing landscape relevant to human disease has been acquired using in vitro cancer cell culture models. The limitation of such in vitro models, however, is that the physiological or disease relevance of results obtained is not necessarily obvious. In this review we focus on discussing in vivo occurring RNA editing events that have been identified in human cancer tissue using samples surgically resected or clinically retrieved from patients. We discuss how RNA editing events occurring in tumours in vivo can identify pathological signalling mechanisms relevant to human cancer physiology which is linked to the different stages of cancer progression including initiation, promotion, survival, proliferation, immune escape and metastasis.The present study was conducted to identify the kinematic variables associated with dolphin kick performance during the acceleration and deceleration phases. Nine male competitive swimmers performed 3-5 × 15-m dolphin kick swimming trials with maximum effort. The underwater motion of the dolphin kick was recorded using a digital video camera for a two-dimensional motion analysis. Upper-lower trunk and leg angles in addition to shoulder, hip, and knee joint angles were calculated as kinematic variables. The average horizontal velocity of the greater trochanter during two cycles of the dolphin kick correlated with the angular displacement of the lower trunk in the acceleration (r = -0.715, p less then 0.05) and deceleration phases (r = 0.682, p less then 0.05). Furthermore, greater angular displacement of the lower trunk was associated with smaller angular displacement of the upper leg and greater angular displacement of the hip, knee, and lower leg in both phases. These results suggest that the movement of the lower trunk is a key kinematic variable for dolphin kick performance, and also that swimming coaches and swimmers need to focus on the movement of the lower trunk as well as upper-lower legs in order to improve dolphin kick motion.Introduction Patients with epilepsy may experience seizure clusters (SCs), which are considered a medical emergency requiring immediate treatment. Besides seizures and seizure-related injuries, patients with SCs experience impaired quality of life and have a greater need for healthcare resources. Midazolam nasal spray (MDZ-NS) was approved by the United States Food and Drug Administration (FDA) for the treatment of SCs in 2019, and was the first FDA-approved nasally administered formulation for treating SCs.Areas covered This article provides a critical evaluation of MDZ-NS for the treatment of patients with SCs. It covers the chemistry, pharmacodynamic and pharmacokinetic properties of MDZ-NS, and safety, tolerability, and efficacy data from phase I and phase III trials. SC treatment guidelines in different countries and for alternative therapies are also discussed.Expert opinion Midazolam is a well-established drug that is familiar to physicians. The newer MDZ-NS formulation offers the benefits of intranasal administration, which allows for outpatient treatment by caregivers and other non-healthcare professionals when an SC occurs, and may be particularly meaningful to patients with limited treatment options because other routes of administration are unsuitable. MDZ-NS is effective and patients are known to return to baseline alertness and psychomotor function within 240 minutes after administration.Postpartum depression (PPD) is a major depressive disorder that affects women during the perinatal period. Our study aimed to evaluate the onset of psychological effects in spontaneous pregnancies in contrast with pregnancies resulting from in vitro fertilization (IVF). We carried out a prospective cohort study using the Edinburgh Postnatal Depression Scale to evaluate postpartum depression. Patients were divided into 3 different groups based on their conception method group A included spontaneous pregnancies, group B included pregnancies after homologous IVF, and group C pregnancies after heterologous IVF. The study included 245 patients. In the first year postpartum the incidence of psychological disorders was different exclusively at discharge from hospital (24.8% A vs. 38.7 B vs. 19% C) [P less then .05] and one year after childbirth (13.3% A vs. 3.4% B vs. 4.8% C) [P less then .05]. The multifactorial analysis showed a significant positive association between psychological distress and advanced maternal age, low parental education, nulliparity, preterm delivery and low fetal weight at birth, multiple pregnancies and multiple births, low pain threshold, and high rate of requesting analgesia intrapartum [P less then .05]. find more Our results suggest a high correlation between PPD and pregnancies resulting from homologous IVF at the time of discharge, whereas there is a higher chance that spontaneous pregnancies develop postpartum depression one year after delivery.The visual system and lifestyle characteristics make the even-toed ungulates an excellent model for the studies of behavioural lateralization. Recent research has focused on these mammals providing evidence of lateralization in a wide range of behaviours. This provides an opportunity for the collation of the current theoretical assumptions and the existing empirical evidence for visual lateralization in artiodactyls. In the present study, we aim first to gain a fuller picture of hemispheric specializations in saiga antelopes by investigating the lateralization of vigilance and novel object inspection in the wild. Second, we summarized the results of the research into visual lateralization in even-toed ungulates and attempted to assess the applicability of two popular hypotheses about the division of hemispheric roles. The results on saigas show a significant preference for head turns to the right visual field during vigilance which was more robust in individuals in larger groups. When an unfamiliar artificial object was placed in their natural setting, saigas preferentially viewed it predominantly with the right eye. These results, together with the cumulative evidence in artiodactyls, do not follow either the approach-withdrawal or positivity-negativity dichotomous patterns widely used to explain the division of functions between the hemispheres.Introduction Osimertinib is a third-generation anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), that irreversibly binds to mutant EGFR, specifically to the T790M EGFR mutant non-small cell lung cancer (NSCLC). Since its approval, osimertinib has been tested in multiple scenarios, including the first-line and adjuvant setting of EGFR-mutant disease.Areas covered The authors summarize the most recent evidence about osimertinib in NSCLC, covering its use as a first-line therapy, its activity on central nervous system metastatic disease, and in elderly patients. Moreover, the authors focus on resistance to this drug and on the therapeutic strategies that may be used to overcome this issue.Expert opinion Osimertinib is a key player in the treatment ofEGFR mutant NSCLC and will probably be used in earlier clinical settings in the future, giving rise to an emerging variety of resistance mechanisms. These could be potentially overcome in several ways e.g. as an oligo-progressive disease local therapy, maintaining osimertinib might be a reasonable option; however, for widespread progressive disease, a switch to chemotherapy should be considered. Finally, either liquid biopsy or tissue biopsy might be considered in patients progressing to osimertinib, as they can lead to the identification of potentially targetable resistance mechanisms.Anemia is common in patients with systemic lupus erythematosus (SLE). The association between thalassemia and SLE is rare. In this study, we report the first patient who was found to have a severe hemolytic anemia caused by combination of SLE and Hb H disease. The patient had a more severe presentation in the hematological system. Our case indicates that for a patient who was diagnosed with SLE and developed deterioration in her hematological cell lines, investigation of other possible coexisting causes would be warranted.Introduction The kinds of costs included in cost-effectiveness analyses (CEAs) for vaccines, such as direct medical costs and indirect costs, may affect their outcomes. While some guidelines recommend inclusion of costs associated with productivity losses/gains, very little guidance is provided about the productivity elements to include and their calculation approach.Areas covered We conducted a systematic review of CEAs for vaccines and vaccine programs published between 1 January 2010 and 19 November 2019 that included productivity costs using Medline, Embase, and the Cochrane Library. The kind of productivity elements included their calculation approach, and the impact of their inclusion on cost-effectiveness are summarized. Among 88 studies identified, productivity elements included were reported for 71 studies (81%) with absenteeism being the most commonly included element. Only 24 studies (27%) reported the approach used to calculate productivity costs (human capital vs. friction approach). Most studies (81%) reported a more favorable cost-effectiveness with the inclusion of productivity losses/gains.Expert opinion Inclusion of productivity losses/gains for CEAs for vaccines has resulted in more favorable cost-effectiveness based on the studies reviewed. However, clearer guidance on the productivity elements to include by disease area and more transparency on the calculation method used may be needed.Introduction Axial osteosarcoma and Ewing sarcoma are rare, aggressive neoplasms with a worse prognosis than with tumors involving the extremities because they are more likely to be associated with larger tumor volumes, older age, primary metastases, and a poor histological response to chemotherapy. The 5-year OS rates are reportedly in the range of 18-41% for axial osteosarcoma, and 46-64% for Ewing sarcoma.Area covered The treatment of axial bone tumors is the same as for extremity bone tumors, and includes chemotherapy, surgery and/or radiotherapy.Expert opinion Local treatment of axial tumors is particularly difficult due to their proximity to neurological and vascular structures, which often makes extensive and en bloc resections impossible without causing significant morbidity. The incidence of local relapse is consequently high, and this is the main issue in the treatment of these tumors. Radiotherapy is an option in the case of surgical resections with close or positive margins, as well as for inoperable tumors.