Immediate versus postponed single blastocyst transfer in modified natural cycle frozen embryo transfer (mNC-FET): a study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Today, it is widespread practice to postpone frozen embryo transfer (FET) in a modified natural cycle (mNC) for at least one menstrual cycle after oocyte retrieval and failed fresh embryo transfer or freeze-all. The rationale behind this practice is the concern that suboptimal ovarian, endometrial or endocrinological conditions following ovarian stimulation may have a negative impact on endometrial receptivity and implantation. However, two recent systematic reviews and meta-analyses based on retrospective data did not support this practice. As unnecessary delay in time to transfer and pregnancy should be avoided, the aim of this study is to investigate if immediate single blastocyst transfer in mNC-FET is non-inferior to standard postponed single blastocyst transfer in mNC-FET in terms of live birth rate. METHODS AND ANALYSIS: Multicentre randomised controlled non-blinded trial including 464 normo-ovulatory women aged 18-40 years undergoing single blastocyst mNC-FET after a failed fresh or freeze-all cycle. Participants are randomised 1:1 to either FET in the first menstrual cycle following the stimulated cycle (immediate FET) or FET in the second or subsequent cycle following the stimulated cycle (postponed FET). The study is designed as a non-inferiority trial and primary analyses will be performed as intention to treat and per protocol. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Scientific Ethical Committee of the Capital Region of Denmark (J-nr.: H-19086300). Data will be handled according to Danish law on personal data protection in accordance with the general data protection regulation. Participants will complete written consent forms regarding participation in the study and storage of blood samples in a biobank for future research. The study will be monitored by a Good Clinical Practice (GCP)-trained study nurse not otherwise involved in the study. The results of this study will be disseminated by publication in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT04748874; Pre-results.

The splicing factor RBM25 controls MYC activity in acute myeloid leukemia.

Cancer sequencing studies have implicated regulators of pre-mRNA splicing as important disease determinants in acute myeloid leukemia (AML), but the underlying mechanisms have remained elusive. We hypothesized that "non-mutated" splicing regulators may also play a role in AML biology and therefore conducted an in vivo shRNA screen in a mouse model of CEBPA mutant AML. This has led to the identification of the splicing regulator RBM25 as a novel tumor suppressor. In multiple human leukemic cell lines, knockdown of RBM25 promotes proliferation and decreases apoptosis. Mechanistically, we show that RBM25 controls the splicing of key genes, including those encoding the apoptotic regulator BCL-X and the MYC inhibitor BIN1. This mechanism is also operative in human AML patients where low RBM25 levels are associated with high MYC activity and poor outcome. Thus, we demonstrate that RBM25 acts as a regulator of MYC activity and sensitizes cells to increased MYC levels.

Heteromeric Slick/Slack K+ channels show graded sensitivity to cell volume changes.

Slick and Slack high-conductance K+ channels are found in the CNS, kidneys, pancreas, among other organs, where they play an important role in cell excitability as well as in ion transport processes. They are both activated by Na+ and Cl- but show a differential regulation by cell volume changes. Slick has been shown to be regulated by cell volume changes, whereas Slack is insensitive. α-subunits of these channels form homomeric as well as heteromeric channels. It is the aim of this work to explore whether the subunit composition of the Slick/Slack heteromeric channel affects the response to osmotic challenges. In order to provide with the adequate water permeability to the cell membrane of Xenopus laevis oocytes, mRNA of aquaporin 1 was co-expressed with homomeric or heteromeric Slick and Slack α-subunits. Oocytes were superfused with hypotonic or hypertonic buffers and changes in currents were measured by two-electrode voltage clamp. This work presents the first heteromeric K+ channel with a characteristic graded sensitivity to small and fast changes in cell volume. Our results show that the cell volume sensitivity of Slick/Slack heteromeric channels is dependent on the number of volume sensitive Slick α-subunits in the tetrameric channels, giving rise to graded cell volume sensitivity. Regulation of the subunit composition of a channel may constitute a novel mechanism to determine volume sensitivity of cells.

Post spinal puncture headache, an old problem and new concepts: review of articles about predisposing factors.

Post spinal puncture headache (PSPH) is a well known complication of spinal anesthesia. It occurs after spinal anesthesia induction due to dural and arachnoid puncture and has a significant effect on the patient's postoperative well being. This manuscript is based on an observational study that runs on Babol University of Medical Sciences and review of literatures about current concepts about the incidence, risk factors and predisposing factors of post spinal puncture headache. The overall incidence of post-dural puncture headache after intentional dural puncture varies form 0.1-36%, while it is about 3.1% by atraumatic spinal needle 25G Whitacre. 25G Quincke needle with a medium bevel cutting is popular with widespread use and the incidence of PSPH is about 25%, but its incidence obtained 17.3% by spinal needle 25G Quincke in our observation. The association of predisposing factors like female, young age, pregnancy, low body mass index, multiple dural puncture, inexpert operators and past medical history of chronic headache, expose the patient to PSPH. The identification of factors that predict the likelihood of PSPH is important so that measures can be taken to minimize this painful complication resulting from spinal anesthesia.

Addition of intrathecal Dexamethasone to Bupivacaine for spinal anesthesia in orthopedic surgery.

OBJECTIVES: Spinal anesthesia has the advantage that profound nerve block can be produced in a large part of the body by the relatively simple injection of a small amount of local anesthetic. Intrathecal local anesthetics have limited duration. Different additives have been used to prolong spinal anesthesia. The effect of corticosteroids in prolonging the analgesic effects of local anesthetics in peripheral nerves is well documented. The purpose of this investigation was to determine whether the addition of dexamethasone to intrathecal bupivacaine would prolong the duration of sensory analgesia or not. METHODS: We conducted a randomized, prospective, double-blind, case-control, clinical trial. A total of 50 patients were scheduled for orthopedic surgery under spinal anesthesia. The patients were randomly allocated to receive 15 mg hyperbaric bupivacaine 0.5% with 2 cc normal saline (control group) or 15 mg hyperbaric bupivacaine 0.5% plus 8 mg dexamethasone (case group) intrathecally. The patients were evaluated for quality, quantity, and duration of block; blood pressure, heart rate, nausea, and vomiting or other complications. RESULTS: There were no signification differences in demographic data, sensory level, and onset time of the sensory block between two groups. Sensory block duration in the case group was 119±10.69 minutes and in the control group was 89.44±8.37 minutes which was significantly higher in the case group (P<0.001). The duration of analgesia was 401.92±72.44 minutes in the case group; whereas it was 202±43.67 minutes in the control group (P<0.001). The frequency of complications was not different between two groups. CONCLUSION: This study has shown that the addition of intrathecal dexamethasone to bupivacaine significantly improved the duration of sensory block in spinal anesthesia without any changes in onset time and complications.