Factors leading to surgical evacuation in first trimester medical termination of pregnancy

Background: Aim of the study was to determine factors leading to surgical evacuation in first trimester medical termination of pregnancy of women attending SAT hospital, medical college, Thiruvananthapuram.Methods: A case control study was conducted at the department of obstetrics and gynaecology, Government Medical college, Thiruvananthapuram. The sample size was calculated to be 58 in each group. Antenatal women attending family planning OPD for termination of pregnancy in first trimester at SAT hospital over a period of one year were recruited for this study. A structured questionnaire was used to record history, examination findings, and investigations including ultrasound. The clinical outcome was defined as successful medical abortion and failed medical abortion which leads to surgical evacuation due to retained products.Results: Previous caesarean, previous induced abortion, previous pregnancy loss or increasing gestational age showed increasing rate of failed medical abortion. Also, in patients with anaemia with haemoglobin <11 gm/dl or diabetes or hypertension showed independent association with failed medical abortion.Conclusions: If patient planning for medical abortion, can do at earlier gestational age as advancing gestation will leads to increasing rate of failed medical abortion and also after correcting anaemia, with proper medication

InMoov-robotin käsivarsien toteutus

Tiivistelmä. Erilaisia robotteja on käytetty jo kauan aikaa. Ensimmäiset robotit tehtiin teolliseen käyttöön, suurimmaksi osaksi liukuhihnatyöhön. Tällaisten robottien ei tarvitse mukautua ympäristöönsä, vaan ympäristö on rakennettu robotin ympärille. Robotiikan ja tekoälyn kehittyessä mahdollistuu myös täysin uudenlaisten robottien valmistus. Robotit voivat mukautua ympäristöönsä paremmin erilaisia sensoreita hyödyntäen. Nykyään robotteja käytetään monenlaiseen tarkoitukseen lääketieteestä autonomisiin autoihin. Robotit voivat olla kalliita suunnitella ja rakentaa, mutta 3d-tulostuksen mahdollistaman halvemman hinnan kautta myös tavallisilla ihmisillä on mahdollista kehittää protyyppejä. Tässä opinnäytetyössä keskitytään robotin rakentamiseen ja kokeiluun, sekä näissä nopean ja edullisen prototyyppien valmistuksen mahdollisuuksiin sekä ongelmiin. Työssä käytetään pohjana InMoov-robotin valmiita 3d-malleja ja Robot Operating System 2 -kirjastoa robotin ohjaamiseen. Näillä malleilla rakennetaan robotin kädet ja ne liitetään jo olemassa olevaan robottiin. Siinä kerrotaan miten servoa voidaan muokata, ja kuinka hammasrattaiden käyttöä voidaan hyödyntää robotin käsien liikuttamiseen. Verrattuna kaupallisiin robotteihin laadussa on eroja, mutta työn tarkoitus on olla esimerkkinä ja tukena muille, jotka haluavat kokeilla rakentaa robotin prototyyppiä edullisesti. 3d-tulostus mahdollistaa uusien osien tulostamisen helposti ja rikkinäiset osat voidaan vaihtaa. Keskeisiä ongelmia robotin rakentamisessa ovat mekaanisten osien heikkous, huonosti toteutetut johdotukset sekä sekava ohjelmistopuoli. Parannus- ja ratkaisuehdotuksia, toteutettuja ratkaisuja, sekä huomioitavia ja vältettäviä asioita esitetään työssä ja lisäksi pohditaan mahdollisia jatkotutkimuskohteita

Neurofilament Light Regulates Axon Caliber, Synaptic Activity, and Organelle Trafficking in Cultured Human Motor Neurons

Neurofilament light (NFL) is one of the proteins forming multimeric neuron-specific intermediate filaments, neurofilaments, which fill the axonal cytoplasm, establish caliber growth, and provide structural support. Dominant missense mutations and recessive nonsense mutations in the neurofilament light gene (NEFL) are among the causes of Charcot–Marie–Tooth (CMT) neuropathy, which affects the peripheral nerves with the longest axons. We previously demonstrated that a neuropathy-causing homozygous nonsense mutation in NEFL led to the absence of NFL in patient-specific neurons. To understand the disease-causing mechanisms, we investigate here the functional effects of NFL loss in human motor neurons differentiated from induced pluripotent stem cells (iPSC). We used genome editing to generate NEFL knockouts and compared them to patient-specific nonsense mutants and isogenic controls. iPSC lacking NFL differentiated efficiently into motor neurons with normal axon growth and regrowth after mechanical axotomy and contained neurofilaments. Electrophysiological analysis revealed that motor neurons without NFL fired spontaneous and evoked action potentials with similar characteristics as controls. However, we found that, in the absence of NFL, human motor neurons 1) had reduced axonal caliber, 2) the amplitude of miniature excitatory postsynaptic currents (mEPSC) was decreased, 3) neurofilament heavy (NFH) levels were reduced and no compensatory increases in other filament subunits were observed, and 4) the movement of mitochondria and to a lesser extent lysosomes was increased. Our findings elaborate the functional roles of NFL in human motor neurons. NFL is not only a structural protein forming neurofilaments and filling the axonal cytoplasm, but our study supports the role of NFL in the regulation of synaptic transmission and organelle trafficking. To rescue the NFL deficiency in the patient-specific nonsense mutant motor neurons, we used three drugs, amlexanox, ataluren (PTC-124), and gentamicin to induce translational read-through or inhibit nonsense-mediated decay. However, the drugs failed to increase the amount of NFL protein to detectable levels and were toxic to iPSC-derived motor neurons

The SET and transposase domain protein Metnase enhances chromosome decatenation: regulation by automethylation

Metnase is a human SET and transposase domain protein that methylates histone H3 and promotes DNA double-strand break repair. We now show that Metnase physically interacts and co-localizes with Topoisomerase IIα (Topo IIα), the key chromosome decatenating enzyme. Metnase promotes progression through decatenation and increases resistance to the Topo IIα inhibitors ICRF-193 and VP-16. Purified Metnase greatly enhanced Topo IIα decatenation of kinetoplast DNA to relaxed circular forms. Nuclear extracts containing Metnase decatenated kDNA more rapidly than those without Metnase, and neutralizing anti-sera against Metnase reversed that enhancement of decatenation. Metnase automethylates at K485, and the presence of a methyl donor blocked the enhancement of Topo IIα decatenation by Metnase, implying an internal regulatory inhibition. Thus, Metnase enhances Topo IIα decatenation, and this activity is repressed by automethylation. These results suggest that cancer cells could subvert Metnase to mediate clinically relevant resistance to Topo IIα inhibitors

High throughput mutagenesis for identification of residues regulating human prostacyclin (hIP) receptor

The human prostacyclin receptor (hIP receptor) is a seven-transmembrane G protein-coupled receptor (GPCR) that plays a critical role in vascular smooth muscle relaxation and platelet aggregation. hIP receptor dysfunction has been implicated in numerous cardiovascular abnormalities, including myocardial infarction, hypertension, thrombosis and atherosclerosis. Genomic sequencing has discovered several genetic variations in the PTGIR gene coding for hIP receptor, however, its structure-function relationship has not been sufficiently explored. Here we set out to investigate the applicability of high throughput random mutagenesis to study the structure-function relationship of hIP receptor. While chemical mutagenesis was not suitable to generate a mutagenesis library with sufficient coverage, our data demonstrate error-prone PCR (epPCR) mediated mutagenesis as a valuable method for the unbiased screening of residues regulating hIP receptor function and expression. Here we describe the generation and functional characterization of an epPCR derived mutagenesis library compromising >4000 mutants of the hIP receptor. We introduce next generation sequencing as a useful tool to validate the quality of mutagenesis libraries by providing information about the coverage, mutation rate and mutational bias. We identified 18 mutants of the hIP receptor that were expressed at the cell surface, but demonstrated impaired receptor function. A total of 38 non-synonymous mutations were identified within the coding region of the hIP receptor, mapping to 36 distinct residues, including several mutations previously reported to affect the signaling of the hIP receptor. Thus, our data demonstrates epPCR mediated random mutagenesis as a valuable and practical method to study the structurefunction relationship of GPCRs. © 2014 Bill et al

Network Clustering Revealed the Systemic Alterations of Mitochondrial Protein Expression

The mitochondrial protein repertoire varies depending on the cellular state. Protein component modifications caused by mitochondrial DNA (mtDNA) depletion are related to a wide range of human diseases; however, little is known about how nuclear-encoded mitochondrial proteins (mt proteome) changes under such dysfunctional states. In this study, we investigated the systemic alterations of mtDNA-depleted (ρ0) mitochondria by using network analysis of gene expression data. By modularizing the quantified proteomics data into protein functional networks, systemic properties of mitochondrial dysfunction were analyzed. We discovered that up-regulated and down-regulated proteins were organized into two predominant subnetworks that exhibited distinct biological processes. The down-regulated network modules are involved in typical mitochondrial functions, while up-regulated proteins are responsible for mtDNA repair and regulation of mt protein expression and transport. Furthermore, comparisons of proteome and transcriptome data revealed that ρ0 cells attempted to compensate for mtDNA depletion by modulating the coordinated expression/transport of mt proteins. Our results demonstrate that mt protein composition changed to remodel the functional organization of mitochondrial protein networks in response to dysfunctional cellular states. Human mt protein functional networks provide a framework for understanding how cells respond to mitochondrial dysfunctions