Complex biological functions emerge through intricate protein-protein interaction networks. An important class of protein-protein interaction corresponds to peptide-mediated interactions, in which a ...short peptide stretch from one partner interacts with a large protein surface from the other partner. Protein-peptide interactions are typically of low affinity and involved in regulatory mechanisms, dynamically reshaping protein interaction networks. Due to the relatively small interaction surface, modulation of protein-peptide interactions is feasible and highly attractive for therapeutic purposes. Unfortunately, the number of available 3D structures of protein-peptide interfaces is very limited. For typical cases where a protein-peptide structure of interest is not available, the PepSite web server can be used to predict peptide-binding spots from protein surfaces alone. The PepSite method relies on preferred peptide-binding environments calculated from a set of known protein-peptide 3D structures, combined with distance constraints derived from known peptides. We present an updated version of the web server that is orders of magnitude faster than the original implementation, returning results in seconds instead of minutes or hours. The PepSite web server is available at http://pepsite2.russelllab.org.
Dengue is the most important arthropod-borne viral disease worldwide. Infection with any of the four dengue virus (DENV) serotypes can be asymptomatic or lead to disease with clinical symptoms ...ranging from undifferentiated and self-limiting fever to severe dengue disease, which can be fatal in some cases. Currently, no specific antiviral compound is available for treating DENV. The aim of this study was to identify compounds in plants from Paraguayan folk medicine with inhibitory effects against DENV. We found high virucidal activity (50% maximal effective concentration (EC50) value of 24.97 µg/mL) against DENV-2 in the ethanolic extract of the roots of Solanum sisymbriifolium Lam. (Solanaceae) without an evident cytotoxic effect on Vero E6 cells. Three saponins isolated from the root extract showed virucidal effects (EC50 values ranging from 24.9 to 35.1 µg/mL) against DENV-2. Additionally, the saponins showed inhibitory activity against yellow fever virus (EC50 values ranging from 126 to 302.6 µg/mL), the prototype virus of the Flavivirus genus, suggesting that they may also be effective against other members of this genus. Consequently, these saponins may be lead compounds for the development of antiviral agents.
OBJECTIVE:To evaluate the association of hysterectomy on ovarian function by comparing antimüllerian hormone, a marker of ovarian reserve, before and after hysterectomy.
METHODS:The Prospective ...Research on Ovarian Function study prospectively followed 1) premenopausal women undergoing ovary-sparing hysterectomy for benign indications, and 2) a referent cohort with similar age distributions and intact reproductive organs; they reported that women undergoing hysterectomy became menopausal 1.9 years earlier than referents. In a planned secondary analysis, baseline antimüllerian hormone levels and the absolute change and percentage change in antimüllerian hormone levels between baseline and 1-year follow-up were compared between groups.
RESULTS:Baseline median antimüllerian hormone levels were similar between the hysterectomy group (n=148) and the referent group (n=172). After 1 year, patients undergoing hysterectomy had a significantly greater median percentage decrease (−40.7% compared with −20.9%; P<.001), had a higher proportion with undetectable antimüllerian hormone (12.8% compared with 4.7%; P=.02), and had on average 0.77 times the antimüllerian hormone level (P=.001) compared with referents. These differences were attenuated among white women but remained significant among black women. Comparisons of women stratified by low or high ovarian reserve at baseline or among propensity score-matched cohorts showed similar findings; however, the absolute median change in antimüllerian hormone levels was similar between groups (−0.3 compared with −0.2; P=.31).
CONCLUSION:Women undergoing hysterectomy had similar antimüllerian hormone levels at baseline and experienced a greater percentage decrease in levels after 1 year compared with referents, suggesting that hysterectomy may lead to ovarian damage that is unrelated to baseline ovarian reserve.
The Learning Curve of Robotic Hysterectomy Woelk, Joshua L; Casiano, Elizabeth R; Weaver, Amy L ...
Obstetrics and gynecology (New York. 1953),
2013-January, 2013-Jan, 2013-01-00, 20130101, Letnik:
121, Številka:
1
Journal Article
Recenzirano
OBJECTIVE:To evaluate the learning curve of robotic hysterectomy using objective, patient-centered outcomes and analytic methods proposed in the literature.
METHODS:All cases of robotic hysterectomy ...performed at Mayo Clinic, Rochester, Minnesota, from January 1, 2007, through December 31, 2009, were collected. Experience was analyzed in 6-month periods. Operative time, complications, and length of stay longer than 1 day were compared between periods for significant change. For learning curve analysis, standard and risk-adjusted cumulative summation charting was used for the two most experienced robotic surgeons (A and B). Outcomes of interest were intraoperative complications and intraoperative or postoperative complications within 6 weeks. Proficiency was defined as the point at which each surgeonʼs curve crossed H0 based on complication rates of abdominal hysterectomy. Cumulative summation parameters were p0=5.7% and p1=11.4% for outcome 1 and p0=36.0% and p1=50% for outcome 2.
RESULTS:In 325 cases, operative time decreased significantly from 3.5 to 2.7 hours during the 3-year period. The proportion of patients with length of stay longer than 1 day decreased significantly from 49.2% to 14.7%. Complications did not decrease significantly. The average number of procedures to cross H0 was 91 for outcome 1 and 44 for outcome 2. Observed cumulative summation curves of surgeons A and B differed from the average number of attempts calculated from p0 and p1.
CONCLUSIONS:Operative time and length of stay decrease with 36 months of experience with robotic hysterectomy, whereas complications may not. Cumulative summation analysis provides an objective, individualized tool to evaluate surgical proficiency and suggests this occurs after performing approximately 91 procedures.
LEVEL OF EVIDENCE:III
Biological molecules are often asymmetric with respect to stereochemistry, and correct stereochemistry is essential to their function. Molecular dynamics simulations of biomolecules have increasingly ...become an integral part of biophysical research. However, stereochemical errors in biomolecular structures can have a dramatic impact on the results of simulations.
Here we illustrate the effects that chirality and peptide bond configuration flips may have on the secondary structure of proteins throughout a simulation. We also analyze the most common sources of stereochemical errors in biomolecular structures and present software tools to identify, correct, and prevent stereochemical errors in molecular dynamics simulations of biomolecules.
Use of the tools presented here should become a standard step in the preparation of biomolecular simulations and in the generation of predicted structural models for proteins and nucleic acids.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To compare perioperative costs and morbidity between open and robotic sacrocolpopexy after implementation of enhanced recovery after surgery (ERAS) pathway.
Methods
The present ...retrospective cohort study of patients undergoing open or robotic sacrocolpopexy (January 1, 2014, through November 30, 2017) used an ERAS protocol with liposomal bupivacaine infiltration of laparotomy incisions. Primary outcomes were costs associated with index surgery and hospitalization, determined with Medicare cost‐to‐charge ratios and reimbursement rates and adjusted for variables expected to impact costs. Secondary outcomes included narcotic use, length of stay (LOS), and complications from index hospitalization to postoperative day 30.
Results
For the total of 231 patients (open cohort, 90; robotic cohort, 141), the adjusted mean cost of robotic surgery was $3239 higher compared with open sacrocolpopexy (95% confidence interval CI $1331–$5147; P < 0.001). Rates were not significantly different for intraoperative complications (robotic, 4.3% 6/141; open, 5.6% 5/90; P = 0.754), 30‐day postoperative complications (robotic, 11.4% 16/141; open, 16.7% 15/90; P = 0.322), or readmissions (robotic, 5.7% 8/141; open, 3.3% 3/90; P = 0.535). The percentage of patients dismissed on postoperative day 1 was greater in the robotic group (89.4% 126/141 vs. 48.9% 44/90, P < 0.001).
Conclusions
Decreased LOS associated with ERAS provided significant cost savings with open sacrocolpopexy versus robotic sacrocolpopexy without adverse impacts on perioperative complications or readmissions.
Synopsis
Decreased length of stay with enhanced recovery after surgery provided significant cost savings for patients undergoing open compared with robotic sacrocolpopexy with similar perioperative outcomes.
A consensus standardized definition of success after stress urinary incontinence surgical treatment is lacking, which precludes comparisons between studies and affects patient counseling.
This study ...aimed to identify optimal patient-centric definition(s) of success after stress urinary incontinence surgical treatment and to compare the identified “more accurate” treatment success definitions with a commonly used composite definition of success (ie, no reported urine leakage, negative cough stress test result, and no retreatment).
We evaluated 51 distinct treatment success definitions for participants enrolled in a previously conducted randomized trial of stress urinary incontinence treatments concomitantly performed with sacrocolpopexy (NCT00934999). For each treatment success definition, we calculated the mean (SD) of participant-assessed symptom improvement and participant-assessed surgical success scores with an 11-point Likert scale among those achieving success and failure. The “more accurate” treatment success definition(s) were identified by measuring the magnitude of the mean difference of participant assessments with Hedges g values. The treatment success definitions with the highest Hedges g values were considered “more accurate” treatment success definitions and were then compared with the composite definition of success.
The percentage of participants who had treatment success (6.4% to 97.3%) and Hedges g values (−4.85 to 1.25) varied greatly according to each treatment success definition. An International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form score ≤5, Urogenital Distress Inventory-6 score ≤33.3, and a no/mild stress urinary incontinence response on Urogenital Distress Inventory-6 question 3 had the highest Hedges g values and were considered the top 3 “more accurate” treatment success definitions. Paradoxically, treatment success definitions that required a negative cough stress test result or no persistent urinary leakage greatly reduced the ability to differentiate between participant-assessed symptom improvement and surgical success. When the “more accurate” treatment success definitions were compared with the composite definition, patients with failed treatment according to the composite definition had lower Urinary Impact Questionnaire-7 scores and a higher proportion of survey responses indicating complete satisfaction or some level of satisfaction and very good/perfect bladder condition. In addition, the composite definition had considerably fewer favorable outcomes for participants than did the top 3 “more accurate” treatment success definitions.
Successful outcomes of stress urinary incontinence surgical treatments for women undergoing concurrent sacrocolpopexy varied greatly depending on the definition used. However, stringent definitions (requiring complete dryness) and objective testing (negative cough stress test result) had decreased, rather than increased, participant-assessed symptom improvement and surgical success scores. The “more accurate” treatment success definitions better differentiated between participant-assessed symptom improvement and surgical success than the composite definition. The composite definition disproportionately misidentified participants who reported minor symptoms or complete/partial satisfaction with their outcome as having treatment failures and yielded a considerably lower proportion of women who reported favorable outcomes than did the top 3 “more accurate” treatment success definitions.
The technique of mutual approximations accurately gives the central instant of the maximum apparent approximation of two moving natural satellites in the plane of the sky. This can be used in ...ephemeris fitting to infer the relative positions of satellites with high precision. Only mutual phenomena-occultations and eclipses-can achieve better results. However, mutual phenomena only occur every six years in the case of Jupiter. Mutual approximations do not have this restriction and can be observed at any time in the year as long as the satellites are visible. In this work, we present 104 central instants determined from the observations of 66 mutual approximations between the Galilean moons carried out at different sites in Brazil and France during the period 2016-2018. For 28 events, we have at least two independent observations. All telescopes were equipped with a narrow-band filter centred at 889 nm with a width of 15 nm to eliminate the scattered light from Jupiter. The telescope apertures ranged between 25 and 120 cm. For comparison, the precision of the positions obtained with classical CCD astrometry is about 100 mas, for mutual phenomena it can be 10 mas or less, and the average internal precision obtained with mutual approximations is 11.3 mas. This new type of simple, yet accurate, observations can significantly improve the orbits and ephemeris of Galilean satellites and thus it can be very useful for the planning of future space missions to the Jovian system.
Enhanced recovery in gynecologic surgery Kalogera, Eleftheria; Bakkum-Gamez, Jamie N; Jankowski, Christopher J ...
Obstetrics and gynecology (New York. 1953),
08/2013, Letnik:
122, Številka:
2 Pt 1
Journal Article
Recenzirano
Odprti dostop
To investigate the effects of enhanced recovery (a multimodal perioperative care enhancement protocol) in patients undergoing gynecologic surgery.
Consecutive patients managed under an enhanced ...recovery pathway and undergoing cytoreduction, surgical staging, or pelvic organ prolapse surgery between June 20, 2011, and December 20, 2011, were compared with consecutive historical controls (March to December 2010) matched by procedure. Wilcoxon rank-sum, χ, and Fisher's exact tests were used for comparisons. Direct medical costs incurred in the first 30 days were obtained from the Olmsted County Healthcare Expenditure and Utilization Database and standardized to 2011 Medicare dollars.
A total of 241 enhanced recovery women in the case group (81 cytoreduction, 84 staging, and 76 vaginal surgery) were compared with women in the control groups. In the cytoreductive group, patient-controlled anesthesia use decreased from 98.7% to 33.3% and overall opioid use decreased by 80% in the first 48 hours with no change in pain scores. Enhanced recovery resulted in a 4-day reduction in hospital stay with stable readmission rates (25.9% of women in the case group compared with 17.9% of women in the control group) and 30-day cost savings of more than $7,600 per patient (18.8% reduction). No differences were observed in rate (63% compared with 71.8%) or severity of postoperative complications (grade 3 or more: 21% compared with 20.5%). Similar, albeit less dramatic, improvements were observed in the other two cohorts. Ninety-five percent of patients rated satisfaction with perioperative care as excellent or very good.
Implementation of enhanced recovery was associated with acceptable pain management with reduced opioids, reduced length of stay with stable readmission and morbidity rates, good patient satisfaction, and substantial cost reductions.
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