The Role of Vaginal Mesh Procedures in Pelvic Organ Prolapse Surgery in View of Complication Risk

Synthetic transvaginal mesh has been employed in the treatment of pelvic organ prolapse for more than a decade. As the use of these devices increased during this period so did adverse event reporting. In 2008, the Food and Drug Administration (FDA) Public Health Notification informed physicians and patients of rising concerns with the use of synthetic transvaginal mesh. Shortly thereafter and in parallel to marked increases in adverse event reporting within the Manufacturer and User Device Experience (MAUDE), the FDA released a Safety Communication regarding urogynecologic surgical mesh use. Following this report and in the wake of increased medical industry product withdrawal, growing medicolegal concerns, patient safety, and clinical practice controversy, many gynecologists and pelvic reconstructive surgeons are left with limited long-term data, clinical guidance, and growing uncertainty regarding the role of synthetic transvaginal mesh use in pelvic organ prolapse. This paper reviews the reported complications of synthetic transvaginal mesh with an evidence-based approach as well as providing suggested guidance for the future role of its use amidst the controversy

Comparison of Vaginal Hysterectomy Techniques and Interventions for Benign Indications: A Systematic Review

OBJECTIVE: To create evidence-based clinical practice guidelines based on a systematic review of published literature regarding the risks and benefits of available preoperative, intraoperative, and postoperative technical steps and interventions at the time of vaginal hysterectomy for benign indications. DATA SOURCES: We systematically searched the literature to identify studies that compared technical steps or interventions during the preoperative, intraoperative, and postoperative periods surrounding vaginal hysterectomy. We searched MEDLINE, Cochrane Central Register of Controlled Trials, Health Technology Assessments, and ClinicalTrials.gov from their inception until April 10, 2016, using the MeSH term "Hysterectomy, Vaginal" and associated text words. We included comparative studies, single-group studies, and systematic reviews published in English. METHODS OF STUDY SELECTION: We double-screened 4,250 abstracts, identifying 60 eligible studies. Discrepancies were adjudicated by a third reviewer. We followed standard systematic review methodology and the Grades for Recommendation, Assessment, Development and Evaluation approach to evaluate the evidence and generate guideline recommendations. TABULATION, INTEGRATION, AND RESULTS: Because of limited literature, only 16 perioperative risks, technical steps, and interventions were identified: obesity, large uteri, prior surgery, gonadotropin-releasing hormone agonists, vaginal antisepsis, bilateral salpingo-oophorectomy, morcellation, apical closure, uterine sealers, hemostatic injectants, hot cone, retractor, cystoscopy, vaginal packing, bladder management, and accustimulation. We organized and reported these as four domains: patient selection, preoperative, intraoperative, and postoperative. We did not identify any patient characteristics precluding a vaginal approach; chlorhexidine or povidone is appropriate for vaginal antisepsis; vasopressin decreases blood loss by 130 cc; tissue-sealing devices decrease blood loss by 44 cc and operative time by 15 minutes with uncertain complication implications; vertical cuff closure results in 1-cm increased vaginal length; either peritoneum or epithelium can be used for colpotomy closure; and routine vaginal packing is not advised. CONCLUSION: Minimal data exist to guide surgeons with respect to planning and performing a vaginal hysterectomy. This study identifies available information and future areas for investigation

Morphological, genomic and transcriptomic responses of Klebsiella pneumoniae to the last-line antibiotic colistin.

Colistin remains one of the few antibiotics effective against multi-drug resistant (MDR) hospital pathogens, such as Klebsiella pneumoniae. Yet resistance to this last-line drug is rapidly increasing. Characterized mechanisms of colR in K. pneumoniae are largely due to chromosomal mutations in two-component regulators, although a plasmid-mediated colR mechanism has recently been uncovered. However, the effects of intrinsic colistin resistance are yet to be characterized on a whole-genome level. Here, we used a genomics-based approach to understand the mechanisms of adaptive colR acquisition in K. pneumoniae. In controlled directed-evolution experiments we observed two distinct paths to colistin resistance acquisition. Whole genome sequencing identified mutations in two colistin resistance genes: in the known colR regulator phoQ which became fixed in the population and resulted in a single amino acid change, and unstable minority variants in the recently described two-component sensor crrB. Through RNAseq and microscopy, we reveal the broad range of effects that colistin exposure has on the cell. This study is the first to use genomics to identify a population of minority variants with mutations in a colR gene in K. pneumoniae.This work was supported by the Wellcome Trust grant number WT098051. The salaries of AKC and CJB were supported by the Medical Research Council [grant number G1100100/1] and MJE is supported by Public Health England. LB is supported by a research fellowship from the Alexander von Humboldt Stiftung/Foundation. KEH is supported by the NHMRC of Australia (Fellowship #1061409)

Normalized Lift: An Energy Interpretation of the Lift Coefficient Simplifies Comparisons of the Lifting Ability of Rotating and Flapping Surfaces

For a century, researchers have used the standard lift coefficient CL to evaluate the lift, L, generated by fixed wings over an area S against dynamic pressure, ½ρv2, where v is the effective velocity of the wing. Because the lift coefficient was developed initially for fixed wings in steady flow, its application to other lifting systems requires either simplifying assumptions or complex adjustments as is the case for flapping wings and rotating cylinders

Prenatal hypoxia induces increased cardiac contractility on a background of decreased capillary density.

Background: Chronic hypoxia in utero (CHU) is one of the most common insults to fetal development and may be associated with poor cardiac recovery from ischaemia-reperfusion injury,yet the effects on normal cardiac mechanical performance are poorly understood. Methods: Pregnant female wistar rats were exposed to hypoxia (12% oxygen, balance nitrogen)for days 10–20 of pregnancy. Pups were born into normal room air and weaned normally. At 10 weeks of age, hearts were excised under anaesthesia and underwent retrograde 'Langendorff' perfusion. Mechanical performance was measured at constant filling pressure (100 cm H2O) with intraventricular balloon. Left ventricular free wall was dissected away and capillary density estimated following alkaline phosphatase staining. Expression of SERCA2a and Nitric Oxide Synthases (NOS) proteins were estimated by immunoblotting. Results: CHU significantly increased body mass (P < 0.001) compared with age-matched control rats but was without effect on relative cardiac mass. For incremental increases in left ventricular balloon volume, diastolic pressure was preserved. However, systolic pressure was significantly greater following CHU for balloon volume = 50 μl (P < 0.01) and up to 200 μl (P < 0.05). For higher balloon volumes systolic pressure was not significantly different from control. Developed pressures were correspondingly increased relative to controls for balloon volumes up to 250 μl (P < 0.05).Left ventricular free wall capillary density was significantly decreased in both epicardium (18%; P <0.05) and endocardium (11%; P < 0.05) despite preserved coronary flow. Western blot analysis revealed no change to the expression of SERCA2a or nNOS but immuno-detectable eNOS protein was significantly decreased (P < 0.001) in cardiac tissue following chronic hypoxia in utero. Conclusion: These data offer potential mechanisms for poor recovery following ischaemia, including decreased coronary flow reserve and impaired angiogenesis with subsequent detrimental effects of post-natal cardiac performance

Interaction-Dependent PCR: Identification of Ligand−Target Pairs from Libraries of Ligands and Libraries of Targets in a Single Solution-Phase Experiment

Interaction-dependent PCR (IDPCR) is a solution-phase method to identify binding partners from combined libraries of small-molecule ligands and targets in a single experiment. Binding between DNA-linked targets and DNA-linked ligands induces formation of an extendable duplex. Extension links codes that identify the ligand and target into one selectively amplifiable DNA molecule. In a model selection, IDPCR resulted in the enrichment of DNA encoding all five known protein−ligand pairs out of 67 599 possible sequences.Chemistry and Chemical Biolog

The KELT Follow-Up Network And Transit False-Positive Catalog: Pre-Vetted False Positives For TESS

The Kilodegree Extremely Little Telescope (KELT) project has been conducting a photometric survey of transiting planets orbiting bright stars for over 10 years. The KELT images have a pixel scale of ~23\u27\u27 pixel⁻¹—very similar to that of NASA\u27s Transiting Exoplanet Survey Satellite (TESS)—as well as a large point-spread function, and the KELT reduction pipeline uses a weighted photometric aperture with radius 3\u27. At this angular scale, multiple stars are typically blended in the photometric apertures. In order to identify false positives and confirm transiting exoplanets, we have assembled a follow-up network (KELT-FUN) to conduct imaging with spatial resolution, cadence, and photometric precision higher than the KELT telescopes, as well as spectroscopic observations of the candidate host stars. The KELT-FUN team has followed-up over 1600 planet candidates since 2011, resulting in more than 20 planet discoveries. Excluding ~450 false alarms of non-astrophysical origin (i.e., instrumental noise or systematics), we present an all-sky catalog of the 1128 bright stars (6 \u3c V \u3c 13) that show transit-like features in the KELT light curves, but which were subsequently determined to be astrophysical false positives (FPs) after photometric and/or spectroscopic follow-up observations. The KELT-FUN team continues to pursue KELT and other planet candidates and will eventually follow up certain classes of TESS candidates. The KELT FP catalog will help minimize the duplication of follow-up observations by current and future transit surveys such as TESS

Measuring the functional sequence complexity of proteins

<p>Abstract</p> <p>Background</p> <p>Abel and Trevors have delineated three aspects of sequence complexity, Random Sequence Complexity (RSC), Ordered Sequence Complexity (OSC) and Functional Sequence Complexity (FSC) observed in biosequences such as proteins. In this paper, we provide a method to measure functional sequence complexity.</p> <p>Methods and Results</p> <p>We have extended Shannon uncertainty by incorporating the data variable with a functionality variable. The resulting measured unit, which we call Functional bit (Fit), is calculated from the sequence data jointly with the defined functionality variable. To demonstrate the relevance to functional bioinformatics, a method to measure functional sequence complexity was developed and applied to 35 protein families. Considerations were made in determining how the measure can be used to correlate functionality when relating to the whole molecule and sub-molecule. In the experiment, we show that when the proposed measure is applied to the aligned protein sequences of ubiquitin, 6 of the 7 highest value sites correlate with the binding domain.</p> <p>Conclusion</p> <p>For future extensions, measures of functional bioinformatics may provide a means to evaluate potential evolving pathways from effects such as mutations, as well as analyzing the internal structural and functional relationships within the 3-D structure of proteins.</p

Screening and Initial Binding Assessment of Fumonisin B1 Aptamers

Fumonisins are mycotoxins produced by Fusarium verticillioides and F. proliferatum, fungi that are ubiquitous in corn (maize). Insect damage and some other environmental conditions result in the accumulation of fumonisins in corn-based products worldwide. Current methods of fumonisin detection rely on the use of immunoaffinity columns and high-performance liquid chromatography (HPLC). The use of aptamers offers a good alternative to the use of antibodies in fumonisin cleanup and detection due to lower costs and improved stability. Aptamers are single-stranded oligonucleotides that are selected using Systematic Evolution of Ligands by EXponential enrichment (SELEX) for their ability to bind to targets with high affinity and specificity. Sequences obtained after 18 rounds of SELEX were screened for their ability to bind to fumonisin B1. Six unique sequences were obtained, each showing improved binding to fumonisin B1 compared to controls. Sequence FB1 39 binds to fumonisin with a dissociation constant of 100 ± 30 nM and shows potential for use in fumonisin biosensors and solid phase extraction columns

Modeling visual-based pitch, lift and speed control strategies in hoverflies

<div><p>To avoid crashing onto the floor, a free falling fly needs to trigger its wingbeats quickly and control the orientation of its thrust accurately and swiftly to stabilize its pitch and hence its speed. Behavioural data have suggested that the vertical optic flow produced by the fall and crossing the visual field plays a key role in this anti-crash response. Free fall behavior analyses have also suggested that flying insect may not rely on graviception to stabilize their flight. Based on these two assumptions, we have developed a model which accounts for hoverflies´ position and pitch orientation recorded in 3D with a fast stereo camera during experimental free falls. Our dynamic model shows that optic flow-based control combined with closed-loop control of the pitch suffice to stabilize the flight properly. In addition, our model sheds a new light on the visual-based feedback control of fly´s pitch, lift and thrust. Since graviceptive cues are possibly not used by flying insects, the use of a vertical reference to control the pitch is discussed, based on the results obtained on a complete dynamic model of a virtual fly falling in a textured corridor. This model would provide a useful tool for understanding more clearly how insects may or not estimate their absolute attitude.</p></div