Synapse Development: Ribonucleoprotein Transport from the Nucleus to the Synapse: A Dissertation

A key process underlying synapse development and plasticity is stimulus-dependent translation of localized mRNAs. This process entails RNA packaging into translationally silent granules and exporting them over long distances from the nucleus to the synapse. Little is know about (a) where ribonucleoprotein (RNP) complexes are assembled, and if in the nucleus, how do they exit the nucleus; (b) how RNPs are transported to specific synaptic sites. At the Drosophila neuromuscular junction (NMJ), we uncovered a novel RNA export pathway for large RNP (megaRNP) granules assembled in the nucleus, which exit the nucleus by budding through the nuclear envelope. In this process, megaRNPs are enveloped by the inner nuclear membrane (INM), travel through the perinuclear space as membrane-bound granules, and are deenveloped at the outer nuclear membrane. We identified Torsin (an AAA-ATPase that in humans is linked to dystonia), as mediator of INM scission. In torsin mutants, megaRNPs accumulate within the perinuclear space, and the mRNAs fail to localize to postsynaptic sites leading to abnormal NMJ development. We also found that nuclear envelope budding is additionally used for RNP export during Drosophila oogenesis. Our studies also suggested that the nuclear envelope-associated protein, Nesprin1, forms striated F-actin-based filaments or ‘‘railroad tracks,’’ that span from muscle nuclei to postsynaptic sites at the NMJ. Nesprin1 railroad tracks wrap aoround the postsynaptic regions of immature synaptic boutons, and serve to direct RNPs to sites of new synaptic bouton formation. These studies elucidate novel cell biological mechanisms for nuclear RNP export and trafficking during synapse development

Reproducibility and repeatability of measuring the electrical impedance of the pregnant human cervix-the effect of probe size and applied pressure

Background: The utility of cervical electrical impedance spectroscopy (EIS) as a diagnostic tool is being investigated in clinical trials. We sought to assess the reliability of two different sizes of tetrapolar probes used in measuring cervical impedance. Methods: Cervical transfer impedance was measured at 14 frequencies between 76 and 625 000 Hz from 11 pregnant subjects at term. Repeated measurements were taken with two probes (3 mm and 12 mm diameter) applied softly (approximately 0.7 Newton of force), and firmly (approximately 2.2 Newton) to the surface of the cervix by two observers. The intra-class correlation coefficient (ICC), coefficient of variation (CV) and repeatability standard deviations (SD) were derived from these measurements and compared. Results: Measurements taken by one observer were highly repeatable for both probes as demonstrated by high ICC and low CV values. Probe performance was improved further by firm application. Firm application of the 3 mm probe resulted in ICC values that ranged from 0.936 to 0.986 (p = 0.0001) and CV values between 1.0 and 3.4%. Firm pressure with the 12 mm probe resulted in ICC values that ranged between 0.914 and 0.988 (p = 0.0001) with CV values between 0.7 and 2.1%. In addition, the repeatability SD was low across all frequencies implying that there was low intra-observer variability. Measurements taken by 2 observers with firm application of the 12 mm probe demonstrated moderate reproducibility between 9.8 and 156 kHz, the frequency range in which previous clinical studies have shown predictive association between high cervical resistivity and vaginal delivery: ICC values ranged between 0.528 and 0.638 (p < 0.05), CV values were between 3.3 and 5.2% and reproducibility SD values were also low. In contrast the 3 mm probe demonstrated poor reproducibility at all study frequencies. Conclusion: Measuring cervical resistivity by a single observer with both the 3 and 12 mm probes is highly repeatable whilst inter-observer reproducibility is poor with the 3 mm probe but moderately good when the 12 mm probe is firmly applied to the cervix in the frequency range 9.8 to 156 kHz, consistent with our observations of probe performance in clinical trials

Final Evaluation Report: Pilot for New Model of Midwifery Supervision

The focus of the evaluation was a bridging programme to prepare existing supervisors of midwives (SOMs) to become professional midwifery advocates (PMAs) in order to deliver a new model of supervision (A-EQUIP). It set out to assess the bridging programme and the A-EQUIP model. This report documents the following stages of the evaluation: 1. Establish baseline data, prior to the adoption of the A-EQUIP pilot a. Development and completion of a site pro-forma to provide contextual organisational data 2. Evaluation of the preparation of the A-EQUIP practitioner and assessment of the A-EQUIP model through the following mechanisms: a. Documentary analysis b. Supervisor/PMA survey c. Supervisee survey d. Supervisor/PMA interview

Clinicopathological study of benign ovarian tumuors

Background: The incidence of ovarian tumor amongst gynecological admissions have been reported to vary from 1-3 %. About 75% of these tumors have been found to be benign. Ovarian malignancies represent the greatest clinical challenge of all the gynecological malignancies. During the reproductive years most of the ovarian tumors encountered are benign. About 2/3 of the ovarian tumors are encountered in this group only. The chance that an ovarian tumor is malignant in a patient younger than 45 years is 1 in 15. The differentiation of the benign from malignant tumors can go wrong even with imaging modalities.CA125 along with ultrasound are useful in differentiating benign from malignant tumors. Histopathological examination is gold standard for diagnosis of ovarian neoplasm.Methods: The present study includes consecutive cases of histopathologically proven ovarian tumors of 3 years from June 2010 to May 2013 reported by the Department of Pathology of our tertiary care center. It includes total 150 cases. After careful study of gross findings, appropriate bits were taken from received ovarian specimen, followed by routine paraffin processing to make H and E stained slides. Special stains were used wherever needed.Results: Majority of the cases 91 (60.67%) were benign, 53 (35.33%) were malignant and 6 (4.0%) were borderline. Surface epithelial tumours were the most common type (68.13%) of ovarian neoplasm in this study. Most of tumours in our study occurred in the age group of 21-40 years. Mucinous cystadenomas were most common benign surface epithelial tumour and most common benign tumors overall. There were 22 cases of benign germ cell tumor, all were mature teratoma. All the sex-cord stromal tumours were diagnosed in women older than 40 years. Most common benign lesion in our study is surface epithelial tumour and in age group of 21-40 years. 84% patients studied had symptoms at presentation, out of which 26% of patient presented with dull/dragging pain. Pan hysterectomy was the most common procedure for surgical management.Conclusions: Most of ovarian neoplasm are benign with mucinous cystadenoma being commonest entity. Commonest age group is 21-40 years. Commonest benign germ cell tumor is Mature cystic teratoma. Commonest clinical symptom is dull/dragging pain. Pan hysterectomy was the most common procedure for surgical management.

Влияние фосфатных связующих на физико-механические свойства периклазохромитовых огнеупоров

У данній статті наведено та порівняно фізико-механічні властивості периклазо-хромітових матеріалів в залежності від різних типів фосфатних зв’язуючих та введення різних домішок. Визначено, що найбільш раціональним є введення триполіфосфату натрію.In given clause are resulted and the physycal-mechanical properties periclase-cgromite of materials are compared depending on different of types phosphate binding and introduction of the various additives. Is determined, that most rational is the introduction treepolyphosphate sodume

Disclosure of donor conception in the era of non-anonymity: safeguarding and promoting the interests of donor-conceived individuals?

This article responds to a debate article published in Human Reproduction earlier this year. In that article, the authors suggested that parents should be encouraged to disclose the use of donor gametes to their children given rapid and widespread advances in genetic testing and sequencing. However, there is an urgent need to engage with the assertion that in this context, telling children about their donor conception both safeguards and promotes their interests, particularly if such disclosure is motivated by parents' anxieties about accidental discovery. Disclosure that is motivated by the notion of non-anonymity may also encourage parents to share misinformation about donors and encourage their children to have unrealistic expectations. Fertility professionals must remain mindful of these outcomes when discussing disclosure and the future implications of increasing access to genetic information with both prospective and current parents. It is strongly advised that future discussions about the end of donor anonymity are not conflated with the debate on disclosure.The Brocher Foundation (Geneva) , Corpus Christi College (Cambridge)This is the author accepted manuscript. The final version is available from Oxford University Press via http://dx.doi.org/10.1093/humrep/dew24

Pregnancy and neonatal outcomes of COVID-19: The PAN-COVID study

Objective To assess perinatal outcomes for pregnancies affected by suspected or confirmed SARS-CoV-2 infection. Methods Prospective, web-based registry. Pregnant women were invited to participate if they had suspected or confirmed SARS-CoV-2 infection between 1st January 2020 and 31st March 2021 to assess the impact of infection on maternal and perinatal outcomes including miscarriage, stillbirth, fetal growth restriction, pre-term birth and transmission to the infant. Results Between April 2020 and March 2021, the study recruited 8239 participants who had suspected or confirmed SARs-CoV-2 infection episodes in pregnancy between January 2020 and March 2021. Maternal death affected 14/8197 (0.2%) participants, 176/8187 (2.2%) of participants required ventilatory support. Pre-eclampsia affected 389/8189 (4.8%) participants, eclampsia was reported in 40/ 8024 (0.5%) of all participants. Stillbirth affected 35/8187 (0.4 %) participants. In participants delivering within 2 weeks of delivery 21/2686 (0.8 %) were affected by stillbirth compared with 8/4596 (0.2 %) delivering ≥ 2 weeks after infection (95 % CI 0.3–1.0). SGA affected 744/7696 (9.3 %) of livebirths, FGR affected 360/8175 (4.4 %) of all pregnancies. Pre-term birth occurred in 922/8066 (11.5%), the majority of these were indicated pre-term births, 220/7987 (2.8%) participants experienced spontaneous pre-term births. Early neonatal deaths affected 11/8050 livebirths. Of all neonates, 80/7993 (1.0%) tested positive for SARS-CoV-2. Conclusions Infection was associated with indicated pre-term birth, most commonly for fetal compromise. The overall proportions of women affected by SGA and FGR were not higher than expected, however there was the proportion affected by stillbirth in participants delivering within 2 weeks of infection was significantly higher than those delivering ≥ 2 weeks after infection. We suggest that clinicians’ threshold for delivery should be low if there are concerns with fetal movements or fetal heart rate monitoring in the time around infection

Cytokines and their receptors in human placental implantation

Available from British Library Document Supply Centre-DSC:D064183 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo