Revision of failed traditional fundoplication using EsophyX® transoral fundoplication

BACKGROUND: Laparoscopic revision of failed traditional fundoplication is difficult and involves risk of gastric, esophageal, and vagal nerve injury that is higher than that of the primary fundoplication. This study assessed feasibility and clinical outcomes of the transoral approach to revision of loose Nissen. METHODS: Between November 2009 and August 2011, a total of 11 patients underwent transoral repair as opposed to 70 patients who underwent laparoscopic or open revision of a failed fundoplication. Subjective and objective outcomes were evaluated with the GERD health-related quality of life (GERD-HRQL) questionnaire and the reflux symptom index (RSI) questionnaire and ambulatory pH testing. The competency of the new antireflux barrier was evaluated by endoscopy. Wilcoxon signed-rank test was used to compare pre- and postoperative variables. RESULTS: All 11 patients evidenced loosening of the Nissen fundoplication without evidence of hiatal failure. Mean age was 57 years, BMI was 25.1 kg/m(2), and 4 of 11 (36 %) were female. Indications for operation were abnormal pH-metry off PPIs (6), impedance/pH on PPIs (3), esophagitis (1), and evidence of free reflux on barium swallow (1). One patient developed a postoperative bleed requiring transfusion. Two patients had laparoscopic revision at 6 and 8 months after the transoral procedure. At a median follow-up of 14 (range = 6–28) months, 8/10 patients reported resolution of their primary symptoms. Eight patients had pH testing off PPIs both pre- and postoperatively; median % time with pH <4 improved by dropping from 8.1 % (21–4.8 %) to 0.6 % (13.4–0.01 %) (p = 0.008). Esophageal acid exposure normalized in 5/6 patients. Mean GERD-HRQL score improved significantly by dropping from 28.6 (10.6) preoperatively to 6.7 (6.1) post-TIF (p = 0.016). Mean RSI score improved more than 50 % in 5/7 patients. CONCLUSION: Transoral revision of failed traditional fundoplication without herniation is technically feasible. It results in symptomatic and objective improvement of GERD without the risks of laparoscopic dissection for a majority of patients

Analysis of the Intrinsically Disordered N-Terminus of the DNA Junction-Resolving Enzyme T7 Endonuclease I:Identification of Structure Formed upon DNA Binding

This work was supported by grants from The Engineering and Physical Sciences Research Council (EPSRC), Basic Technology EP/F039034/1, The Wellcome Trust, 099149/Z/12/Z, and Cancer Research UK (CRUK), C28/A18604.The four-way (Holliday) DNA junction of homologous recombination is processed by the symmetrical cleavage of two strands by a nuclease. These junction-resolving enzymes bind to four-way junctions in dimeric form, distorting the structure of the junction in the process. Crystal structures of T7 endonuclease I have been determined as free protein, and the complex with a DNA junction. In neither crystal structure was the N-terminal 16-amino acid peptide visible, yet deletion of this peptide has a marked effect on the resolution process. Here we have investigated the N-terminal peptide by inclusion of spin-label probes at unique sites within this region, studied by electron paramagnetic resonance. Continuous wave experiments show that these labels are mobile in the free protein but become constrained on binding a DNA junction, with the main interaction occurring for residues 7-10 and 12. Distance measurements between equivalent positions within the two peptides of a dimer using PELDOR showed that the intermonomeric distances for residues 2-12 are long and broadly distributed in the free protein but are significantly shortened and become more defined on binding to DNA. These results suggest that the N-terminal peptides become more organized on binding to the DNA junction and nestle into the minor grooves at the branchpoint, consistent with the biochemical data indicating an important role in the resolution process. This study demonstrates the presence of structure within a protein region that cannot be viewed by crystallography.Publisher PDFPeer reviewe

Female Sexual Function Index Short Version: A MsFLASH Item Response Analysis

The Female Sexual Function Index (FSFI) is a psychometrically sound and popular 19-item self-report measure, but its length may preclude its use in studies with multiple outcome measures, especially when sexual function is not a primary endpoint. Only one attempt has been made to create a shorter scale, resulting in the Italian FSFI-6, later translated into Spanish and Korean without further psychometric analysis. Our study evaluated whether a subset of items on the 19-item English-language FSFI would perform as well as the full-length FSFI in peri- and post-menopausal women. We used baseline data from 898 peri- and post-menopausal women recruited from multiple communities, ages 42–62 years, and enrolled in randomized controlled trials for vasomotor symptom management. Goals were to (1) create a psychometrically sound, shorter version of the FSFI for use in peri- and post-menopausal women as a continuous measure and (2) compare it to the Italian FSFI-6. Results indicated that a 9-item scale provided more information than the FSFI-6 across a spectrum of sexual functioning, was able to capture sample variability, and showed sufficient range without floor or ceiling effects. All but one of the items from the Italian 6-item version were included in the 9-item version. Most omitted FSFI items focused on frequency of events or experiences. When assessment of sexual function is a secondary endpoint and subject burden related to questionnaire length is a priority, the 9-item FSFI may provide important information about sexual function in English-speaking peri- and post-menopausal women

Association of magnetic resonance assessed disc degeneration and late clinical recurrence in dogs treated surgically for thoracolumbar intervertebral disc extrusions

BackgroundRadiographic signs of intervertebral disc mineralization are thought to indicate sites of future recurrence of disc extrusion (Hansen type I) but the relationship between evidence of disc degeneration on magnetic resonance imaging (MRI) and future disc extrusion with recurrence of clinical signs has not been examined.ObjectivesTo examine the relationship between MRI-assessed degeneration of thoracolumbar intervertebral discs and late recurrence of clinical signs in dogs presented with acute thoracolumbar intervertebral disc extrusion and treated by hemilaminectomy alone.AnimalsNinety-two client-owned dogs presented to 2 referral hospitals between 2009 and 2014.MethodsRetrospective analysis of association between clinical signs consistent with recurrent thoracolumbar intervertebral disc extrusion and MRI evidence of disc degeneration in dogs undergoing hemilaminectomy for acute thoracolumbar intervertebral disc extrusion. Univariable and multivariable Cox regression analyses were used to explore associations between recurrence of clinical signs and several characteristics of T10-L3 discs at initial diagnosis.ResultsNinety-two cases were included, of which 42 (46%) were Dachshunds and median age was 5.3 years. Clinical signs recurred in 33/92 (36%) dogs. Finding a completely degenerate disc in the T10 to L3 region (in addition to the operated site) at the time of surgery was associated with a hazard ratio of 2.92 (95% confidence interval: 1.37-6.20) for recurrence of clinical signs.Conclusions and clinical importanceOur results suggest that in cases of thoracolumbar intervertebral disc extrusion in dogs, recurrence of signs is likely if at least 1 completely degenerate disc in addition to the currently symptomatic disc is visible on MRI

Menopausal Quality of Life: A RCT of Yoga, Exercise and Omega-3 Supplements

Objective— Determine efficacy of three non-hormonal therapies for improving menopause- related quality of life (QOL) in women with vasomotor symptoms (VMS). Methods— 12-week 3×2 randomized, controlled, factorial design trial. Peri- and postmenopausal women, ages 40-62 years, were randomized to yoga (n=107), exercise (n=106), or usual activity (n=142), and also randomized to double-blind comparison of omega-3 (n=177) or placebo (n=178) capsules. Interventions: 1) weekly 90-minute yoga classes with daily at-home practice; 2) individualized facility-based aerobic exercise training 3 times/week; and 3) 0.615 gram omega-3 supplement, 3 times/day. Outcomes: Menopausal Quality of Life Questionnaire (MENQOL) total and domain (VMS, psychosocial, physical and sexual) scores. Results— Among 355 randomized women, average age 54.7 years, 338 (95%) completed 12- week assessments. Mean baseline VMS frequency was 7.6/day and mean baseline total MENQOL score was 3.8 (range 1-8 from better to worse) with no between-group differences. For yoga compared to usual activity, baseline to 12-week improvements were seen for MENQOL total -0.3 (95% CI -0.6 to 0.0, p=0.02), and VMS (p=0.02) and sexuality (p=0.03) domain scores. For exercise and omega-3 compared to controls, improvements in baseline to 12-week total MENQOL scores were not observed. Exercise showed benefit in the MENQOL physical domain score at 12- weeks (p=0.02). Conclusion— All women become menopausal and many seek medical advice on ways to improve quality of life; little evidence-based information exists. We found, among healthy sedentary menopausal women, yoga appears to improve menopausal QOL - the clinical significance of our finding is uncertain due to modest effect

Reconstructing Video from Interferometric Measurements of Time-Varying Sources

Very long baseline interferometry (VLBI) makes it possible to recover images of astronomical sources with extremely high angular resolution. Most recently, the Event Horizon Telescope (EHT) has extended VLBI to short millimeter wavelengths with a goal of achieving angular resolution sufficient for imaging the event horizons of nearby supermassive black holes. VLBI provides measurements related to the underlying source image through a sparse set spatial frequencies. An image can then be recovered from these measurements by making assumptions about the underlying image. One of the most important assumptions made by conventional imaging methods is that over the course of a night's observation the image is static. However, for quickly evolving sources, such as the galactic center's supermassive black hole (Sgr A*) targeted by the EHT, this assumption is violated and these conventional imaging approaches fail. In this work we propose a new way to model VLBI measurements that allows us to recover both the appearance and dynamics of an evolving source by reconstructing a video rather than a static image. By modeling VLBI measurements using a Gaussian Markov Model, we are able to propagate information across observations in time to reconstruct a video, while simultaneously learning about the dynamics of the source's emission region. We demonstrate our proposed Expectation-Maximization (EM) algorithm, StarWarps, on realistic synthetic observations of black holes, and show how it substantially improves results compared to conventional imaging algorithms. Additionally, we demonstrate StarWarps on real VLBI data of the M87 Jet from the VLBA

Prenatal Treatment for Serious Neurological Sequelae of Congenital Toxoplasmosis: An Observational Prospective Cohort Study

Background: The effectiveness of prenatal treatment to prevent serious neurological sequelae (SNSD) of congenital toxoplasmosis is not known.Methods and Findings: Congenital toxoplasmosis was prospectively identified by universal prenatal or neonatal screening in 14 European centres and children were followed for a median of 4 years. We evaluated determinants of postnatal death or SNSD defined by one or more of functional neurological abnormalities, severe bilateral visual impairment, or pregnancy termination for confirmed congenital toxoplasmosis. Two-thirds of the cohort received prenatal treatment (189/293; 65%). 23/293 (8%) fetuses developed SNSD of which nine were pregnancy terminations. Prenatal treatment reduced the risk of SNSD. The odds ratio for prenatal treatment, adjusted for gestational age at maternal seroconversion, was 0.24 (95% Bayesian credible intervals 0.07-0.71). This effect was robust to most sensitivity analyses. The number of infected fetuses needed to be treated to prevent one case of SNSD was three (95% Bayesian credible intervals 2-15) after maternal seroconversion at 10 weeks, and 18 (9-75) at 30 weeks of gestation. Pyrimethamine-sulphonamide treatment did not reduce SNSD compared with spiramycin alone (adjusted odds ratio 0.78, 0.21-2.95). The proportion of live-born infants with intracranial lesions detected postnatally who developed SNSD was 31.0% (17.0%-38.1%).Conclusion: The finding that prenatal treatment reduced the risk of SNSD in infected fetuses should be interpreted with caution because of the low number of SNSD cases and uncertainty about the timing of maternal seroconversion. As these are observational data, policy decisions about screening require further evidence from a randomized trial of prenatal screening and from cost-effectiveness analyses that take into account the incidence and prevalence of maternal infection

The effects of Acute Δ9-tetrahydrocannabinol on striatal glutamatergic function: a proton magnetic resonance spectroscopy study

Background: Cannabis and its main psychoactive component, Δ9-tetrahydrocannabinol (THC), can elicit transient psychotic symptoms. A key candidate biological mechanism of how THC induces psychotic symptoms is the modulation of glutamate in the brain. We sought to investigate the effects of acute THC administration on striatal glutamate levels and its relationship to the induction of psychotic symptoms. Methods: We used proton magnetic resonance spectroscopy to measure glutamate levels in the striatum in 20 healthy participants after THC (15 mg, oral) and matched placebo administration in a randomized, double-blind, placebo-controlled design. Psychotic symptoms were measured using the Psychotomimetic States Inventory. Results: We found that THC administration did not significantly change glutamate (glutamate plus glutamine relative to creatine) concentration in the striatum (p =.58; scaled Jeffreys-Zellner-Siow Bayes factor = 4.29). THC increased psychotic symptoms, but the severity of these symptoms was not correlated with striatal glutamate levels. Conclusions: These findings suggest that oral administration of 15 mg of THC does not result in altered striatal glutamate levels. Further work is needed to clarify the effects of THC on striatal glutamate

Pooled Analysis of Six Pharmacologic and Nonpharmacologic Interventions for Vasomotor Symptoms

Objective: To describe the effects of six interventions for menopausal vasomotor symptoms relative to control in a pooled analysis, facilitating translation of the results for clinicians and symptomatic women. The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network tested these interventions in three randomized clinical trials. Methods: An analysis of pooled individual-level data from three randomized clinical trials is presented. Participants were 899 perimenopausal and postmenopausal women with at least 14 bothersome vasomotor symptoms per week. Interventions included 10-20 mg escitalopram per day, nonaerobic yoga, aerobic exercise, 1.8 g per day omega-3 fatty acid supplementation, 0.5 mg low-dose oral 17-beta-estradiol (E2) per day, and 75 mg low-dose venlafaxine XR per day. The main outcome measures were changes from baseline in mean daily vasomotor symptom frequency and bother during 8-12 weeks of treatment. Linear regression models estimated differences in outcomes between each intervention and corresponding control group adjusted for baseline characteristics. Models included trial-specific intercepts, effects of the baseline outcome measure, and time. Results: The 8-week reduction in vasomotor symptom frequency from baseline relative to placebo was similar for escitalopram at -1.4 per day (95% confidence interval [CI] -2.7 to -0.2), low-dose E2 at -2.4 (95% CI -3.4 to -1.3), and venlafaxine at -1.8 (95% CI -2.8 to -0.8); vasomotor symptom bother reduction was minimal and did not vary across these three pharmacologic interventions (mean -0.2 to -0.3 relative to placebo). No effects on vasomotor symptom frequency or bother were seen with aerobic exercise, yoga, or omega-3 supplements. Conclusion: These analyses suggest that escitalopram, low-dose E2, and venlafaxine provide comparable, modest reductions in vasomotor symptom frequency and bother among women with moderate hot flushes