Aim
Minimally invasive approaches to proctectomy for rectal cancer have not been widely adopted due to inherent technical challenges. A modification of traditional transabdominal mobilization, termed ...transanal total mesorectal excision (TaTME), has the potential to improve access to the distal rectum. The aim of the current study is to assess outcomes following TaTME for rectal cancer.
Method
This is a retrospective analysis of a prospectively maintained database of consecutive patients who underwent TaTME for rectal cancer at a single institution. The study period was from 1 March 2012 to 31 July 2015.
Results
During the study period 50 patients underwent TaTME. The median tumour distance from the anal verge was 4.4 (3.0–5.5) cm. The rate of conversion from a planned minimally invasive approach was 2.2%. The median operative time was 267.0 (227.0–331.0) min. The median lymph node yield was 18.0 (12.0–23.8), the macroscopic quality assessment of the resected specimen was incomplete in 2% and the circumferential resection margin positivity rate was 4%. Intra‐operative morbidity occurred in 6% and the 30 day morbidity rate was 36%. The median length of stay was 4.5 (4.0–8.0) days. The median follow‐up was 15.1 (7.0–23.2) months; two patients have developed a local recurrence and eight patients have developed distant recurrence.
Conclusion
These data suggest that TaTME for rectal cancer is feasible with an acceptable pathological outcome and morbidity profile. Further data on functional and long‐term survival outcomes are required.
•CycLuc1 outperforms D-luciferin for bioluminescence imaging in live mice.•Luciferin substrates can be formed by reaction of component parts in vivo.•Caged luciferins can report on cellular ...proximity.•Caged luciferins can report on multiple enzymatic activities or analytes.•Enzymes from nonluminescent organisms can function as luciferases.
The light-emitting chemical reaction catalyzed by the enzyme firefly luciferase is widely used for noninvasive imaging in live mice. However, photon emission from the luciferase is crucially dependent on the chemical properties of its substrate, D-luciferin. In this review, we describe recent work to replace the natural luciferase substrate with synthetic analogs that extend the scope of bioluminescence imaging.
The multi-band template analysis (MBTA) pipeline is a low-latency coincident analysis pipeline for the detection of gravitational waves (GWs) from compact binary coalescences. MBTA runs with a low ...computational cost, and can identify candidate GW events online with a sub-minute latency. The low computational running cost of MBTA also makes it useful for data quality studies. Events detected by MBTA online can be used to alert astronomical partners for electromagnetic follow-up. We outline the current status of MBTA and give details of recent pipeline upgrades and validation tests that were performed in preparation for the first advanced detector observing period. The MBTA pipeline is ready for the outset of the advanced detector era and the exciting prospects it will bring.
Although the zebrafish is a major model organism, how they determine sex is not well understood. In domesticated zebrafish, sex determination appears to be polygenic, being influenced by multiple ...genetic factors that may vary from strain to strain, and additionally can be influenced by environmental factors. However, the requirement of germ cells for female sex determination is well documented: animals that lack germ cells, or oocytes in particular, develop exclusively as males. Recently, it has been determined that oocytes are also required throughout the adult life of the animal to maintain the differentiated female state. How oocytes control sex differentiation and maintenance of the sexual phenotype is unknown. We therefore generated targeted mutations in genes for two oocyte produced signaling molecules, Bmp15 and Gdf9 and here report a novel role for Bmp15 in maintaining adult female sex differentiation in zebrafish. Females deficient in Bmp15 begin development normally but switch sex during the mid- to late- juvenile stage, and become fertile males. Additionally, by generating mutations in the aromatase cyp19a1a, we show that estrogen production is necessary for female development and that the function of Bmp15 in female sex maintenance is likely linked to the regulation of estrogen biosynthesis via promoting the development of estrogen-producing granulosa cells in the oocyte follicle.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bioluminescence imaging is a powerful approach for visualizing specific events occurring inside live mice. Animals can be made to glow in response to the expression of a gene, the activity of an ...enzyme, or the growth of a tumor. But bioluminescence requires the interaction of a luciferase enzyme with a small‐molecule luciferin, and its scope has been limited by the mere handful of natural combinations. Herein, we show that mutants of firefly luciferase can discriminate between natural and synthetic substrates in the brains of live mice. When using adeno‐associated viral (AAV) vectors to express luciferases in the brain, we found that mutant luciferases that are inactive or weakly active with d‐luciferin can light up brightly when treated with the aminoluciferins CycLuc1 and CycLuc2 or their respective FAAH‐sensitive luciferin amides. Further development of selective luciferases promises to expand the power of bioluminescence and allow multiple events to be imaged in the same live animal.
Glowing mutant brains: Bioluminescence requires the interaction of a luciferase enzyme with a small‐molecule luciferin, and its scope has been limited by the mere handful of natural combinations. Firefly luciferase mutants were developed that can discriminate between natural and synthetic substrates in the brains of live mice.
Firefly luciferase is the most widely used optical reporter for noninvasive bioluminescence imaging (BLI) in rodents. BLI relies on the ability of the injected luciferase substrate D-luciferin to ...access luciferase-expressing cells and tissues within the animal. Here we show that injection of mice with a synthetic luciferin, CycLuc1, improves BLI with existing luciferase reporters and enables imaging in the brain that could not be achieved with D-luciferin.
Bioluminescence occurs when an enzyme, known as a luciferase, oxidizes a small‐molecule substrate, known as a luciferin. Nature has evolved multiple distinct luciferases and luciferins independently, ...all of which accomplish the impressive feat of light emission. One of the best‐known examples of bioluminescence is exhibited by fireflies, a class of beetles that use d‐luciferin as their substrate. The evolution of bioluminescence in beetles is thought to have emerged from ancestral fatty acyl‐CoA synthetase (ACS) enzymes present in all insects. This theory is supported by multiple lines of evidence: Beetle luciferases share high sequence identity with these enzymes, often retain ACS activity, and some ACS enzymes from nonluminous insects can catalyze bioluminescence from synthetic d‐luciferin analogues. Recent sequencing of firefly genomes and transcriptomes further illuminates how the duplication of ACS enzymes and subsequent diversification drove the evolution of bioluminescence. These genetic analyses have also uncovered candidate enzymes that may participate in luciferin metabolism. With the publication of the genomes and transcriptomes of fireflies and related insects, we are now better positioned to dissect and learn from the evolution of bioluminescence in beetles.
Why can fireflies glow, but most insects cannot? Firefly bioluminescence requires a small molecule, d‐luciferin, and the enzyme luciferase. Nonluminous insects express enzymes that are closely related to luciferase, but they lack its unique substrate. Here, we discuss how bioluminescence may have evolved via the enzymatic promiscuity of fatty acid‐adenylating enzymes and the biosynthesis of an oxygen‐reactive luminogenic molecule.
Spin manipulation using electric currents is one of the most promising directions in the field of spintronics. We used neutron scattering to observe the influence of an electric current on the ...magnetic structure in a bulk material. In the skyrmion lattice of manganese silicon, where the spins form a lattice of magnetic vortices similar to the vortex lattice in type II superconductors, we observe the rotation of the diffraction pattern in response to currents that are over five orders of magnitude smaller than those typically applied in experimental studies on current-driven magnetization dynamics in nanostructures. We attribute our observations to an extremely efficient coupling of inhomogeneous spin currents to topologically stable knots in spin structures.
Clinical prediction rules Adams, Simon T; Leveson, Stephen H
BMJ,
01/2012, Letnik:
344, Številka:
7842
Journal Article
Recenzirano
Odprti dostop
Clinical prediction rules are mathematical tools that are intended to guide clinicians in their everyday decision making. The popularity of such rules has increased greatly over the past few years. ...This article outlines the concepts underlying their development and the pros and cons of their use
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