Hydrogels can be equipped with functional groups for specific purposes. Isothiouronium groups can enhance adsorptivity, or allow coupling of other functional groups through mild reactions after ...transformation to thiol groups. Here we present a method to prepare multifunctional hydrogels by introducing isothiouronium groups into poly(ethylene glycol) diacrylate (PEGDA) hydrogels, and convert them into thiol-functionalized hydrogels by the reduction of the isothiouronium groups. For this purpose, the amphiphilic monomer 2-(11-(acryloyloxy)-undecyl)isothiouronium bromide (AUITB), containing an isothiouronium group, was synthesized and copolymerized with PEGDA. In this convenient way, it was possible to incorporate up to 3 wt% AUITB into the hydrogels without changing their equilibrium swelling degree. The successful functionalization was demonstrated by surface analysis of the hydrogels with water contact angle measurements and increased isoelectric points of the hydrogel surfaces from 4.5 to 9.0 due to the presence of the isothiouronium groups. The hydrogels showed a suitability as an adsorbent, as exemplified by the pronounced adsorption of the anionic drug diclofenac. The potential of the functionalization for (bio)conjugation reactions was demonstrated by the reduction of isothiouronium groups to thiols and subsequent immobilization of the functional enzyme horseradish peroxidase on the hydrogels. The results show that fully accessible isothiouronium groups can be introduced into radically cross-linked hydrogels.
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•Benchmarking the E. coli S30 lysate core proteome.•Classification of proteome subsets relevant for cell-free expression.•Tuning S30 cell-free lysate production for improved protein ...quality.•Quantitative proteome analysis of SOS response induced S30 lysates.
Protein production using processed cell lysates is a core technology in synthetic biology and these systems are excellent to produce difficult toxins or membrane proteins. However, the composition of the central lysate of cell-free systems is still a “black box”. Escherichia coli lysates are most productive for cell-free expression, yielding several mgs of protein per ml of reaction. Their preparation implies proteome fractionation, resulting in strongly biased and yet unknown lysate compositions. Many metabolic pathways are expected to be truncated or completely removed. The lack of knowledge of basic cell-free lysate proteomes is a major bottleneck for directed lysate engineering approaches as well as for assay design using non-purified reaction mixtures.
This study is starting to close this gap by providing a blueprint of the S30 lysate proteome derived from the commonly used E. coli strain A19. S30 lysates are frequently used for cell-free protein production and represent the basis of most commercial E. coli cell-free expression systems. A fraction of 821 proteins was identified as the core proteome in S30 lysates, representing approximately a quarter of the known E. coli proteome. Its classification into functional groups relevant for transcription/translation, folding, stability and metabolic processes will build the framework for tailored cell-free reactions. As an example, we show that SOS response induction during cultivation results in tuned S30 lysate with better folding capacity, and improved solubility and activity of synthesized proteins. The presented data and protocols can serve as a platform for the generation of customized cell-free systems and product analysis.
Untreated, one third of patients who undergo surgery will have postoperative nausea and vomiting. Although many trials have been conducted, the relative benefits of prophylactic antiemetic ...interventions given alone or in combination remain unknown.
We enrolled 5199 patients at high risk for postoperative nausea and vomiting in a randomized, controlled trial of factorial design that was powered to evaluate interactions among as many as three antiemetic interventions. Of these patients, 4123 were randomly assigned to 1 of 64 possible combinations of six prophylactic interventions: 4 mg of ondansetron or no ondansetron; 4 mg of dexamethasone or no dexamethasone; 1.25 mg of droperidol or no droperidol; propofol or a volatile anesthetic; nitrogen or nitrous oxide; and remifentanil or fentanyl. The remaining patients were randomly assigned with respect to the first four interventions. The primary outcome was nausea and vomiting within 24 hours after surgery, which was evaluated blindly.
Ondansetron, dexamethasone, and droperidol each reduced the risk of postoperative nausea and vomiting by about 26 percent. Propofol reduced the risk by 19 percent, and nitrogen by 12 percent; the risk reduction with both of these agents (i.e., total intravenous anesthesia) was thus similar to that observed with each of the antiemetics. All the interventions acted independently of one another and independently of the patients' baseline risk. Consequently, the relative risks associated with the combined interventions could be estimated by multiplying the relative risks associated with each intervention. Absolute risk reduction, though, was a critical function of patients' baseline risk.
Because antiemetic interventions are similarly effective and act independently, the safest or least expensive should be used first. Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may benefit from a single intervention, and multiple interventions should be reserved for high-risk patients.
In cancer follow-up, in addition to the evaluation of survival probabilities, there is a fundamental need of assessing recurrence dynamics for optimal disease management. Although the time-dependent ...effect of the oestrogen receptor (ER) status of the tumour has already been described, so far no factor has proven to disentangle the multi-peak behaviour observed for breast cancer recurrences. Here, we aimed at investigating whether adiposity at diagnosis, reflected by increased patient's body mass index (BMI), could be associated with breast cancer recurrence patterns over time after primary cancer therapy.
We retrieved BMI from 734 of 777 patients with node-positive breast cancer from a phase III randomised clinical trial, which compared different chemotherapy regimens and had a median follow-up of 15.4 years. Cumulative incidence estimation as well as piecewise exponential models were carried out to estimate the distant recurrence dynamics, in all patients, as well as in subgroups based on the ER status, with the ER-positive group being further split according to the menopausal status.
In patients with ER-negative breast cancer, time-dependent analyses revealed that the hazard of late relapses could mainly be attributed to the overweight and obese patients. Within the subgroup of premenopausal patients with ER-positive tumours, obesity was associated with an early high narrow peak of distant recurrences followed by another main peak after 5 years of follow-up. The risk for overweight patients was intermediate between obese and normal-weight patients. In the postmenopausal subgroup of patients with ER-positive tumours, the distant recurrence rate was significantly more elevated in the overweight patients compared to the other BMI categories, and a second late peak of recurrences was also observed for the obese patients.
These results demonstrate that the patient's BMI at diagnosis is associated with cancer recurrence dynamics. Patient adiposity should therefore be central to the exploration of late adjuvant treatment modalities.
•The body mass index (BMI) at diagnosis is influencing breast cancer recurrence patterns over time.•Late relapses could mainly be attributed to the overweight and obese patients in the oestrogen-receptor negative disease.•Obese patients display a first high peak of recurrence followed by a delayed clustering of late distant events.•These findings support the consideration of patient's BMI for adequate treatment management over time.
Abstract Study Objective To evaluate strategies to treat postoperative nausea and vomiting (PONV) in patients undergoing elective breast surgery. Design Prospective, randomized, double-blinded, ...placebo-controlled trial. Setting University-affiliated hospital. Patients 480 patients with risk factors for PONV. Interventions Patients were randomized to three groups to receive an antiemetic prophylactic combination of haloperidol and tropisetron (Group HT), dimenhydrinate and dexamethasone (Group DD), or no prophylaxis (Group P). Anesthesia was maintained with volatile anesthesia (desflurane or sevoflurane) and fentanyl or total intravenous anesthesia (TIVA). Measurements Incidence of nausea, emesis, or both in the early (0 - 2 hrs) and late (2 - 24 hrs) postoperative periods were recorded, as were the number of episodes and the time of each occurrence; and patient assessment of the PONV experience on a scale comparable to a numeric rating scale (NRS). Main Results Both antiemetic combinations significantly reduced PONV incidence. In patients who received no prophylaxis, PONV incidence was 48.2% in patients given volatile anesthetics and 43.8% in those who received TIVA. PONV incidence was 17.5% in the Group HT patients who received volatile anesthetics, and 25% in the Group HT patients who received TIVA. PONV incidence was 11.4% in Group DD patients given volatile anesthetics, and 15% in Group DD patients receiving TIVA. TIVA reduced the incidence of PONV in the early postoperative period (0-2 hrs), but increased PONV incidence in the late period (2-24 hrs). Patients given TIVA with propofol and remifentanil intraoperatively required more opioids postoperatively than patients given volatile anesthetics. Conclusion The frequency of PONV was reduced significantly with both antiemetic combinations.
Mechanical properties of metallic materials are often optimized by a specific heat treatment to adjust a required grain size. Thereby solute atoms, impurities or precipitates play an important role ...due to their retarding forces on the grain boundary movement. However, they not only stabilize small grain sizes during a heat treatment, it is also suggested that they introduce abnormal grain growth whereby for a small amount of grains the grain size increases tenfold and more. On the one hand abnormal grain growth impedes the adjustment of a required grain size; on the other hand it can be used to introduce bimodal grain structures which are known to combine opposing mechanical properties such as a high toughness and a high ductility. Therefore, the mechanisms of abnormal grain growth are investigated by varying the content of additives during the deposition process. Particle pinning is suggested as the mechanism responsible for abnormal grain growth at least in the initial stage, while a second phase may introduce extraordinary cubic grains growing abnormally in the late stage.
This paper introduces the CableRobot simulator, which was developed at the Max Planck Institute for Biological Cybernetics in cooperation with the Fraunhofer Institute for Manufacturing Engineering ...and Automation IPA. The simulator is a completely novel approach to the design of motion simulation platforms in so far as it uses cables and winches for actuation instead of rigid links known from hexapod simulators. This approach allows to reduce the actuated mass, scale up the workspace significantly, and provides great flexibility to switch between system configurations in which the robot can be operated. The simulator will be used for studies in the field of human perception research and virtual reality applications. The paper discusses some of the issues arising from the usage of cables and provides a system overview regarding kinematics and system dynamics as well as giving a brief introduction into possible application use cases.
Routine use of a nasogastric (NG) tube has been suggested to prevent postoperative nausea and vomiting (PONV) despite conflicting data. Accordingly, we tested the hypothesis that routine use of a NG ...tube does not reduce PONV. Our work is based on data from a large trial of 4055 patients initially designed to quantify the effectiveness of combinations of antiemetic treatments for the prevention of PONV. This analysis uses propensity scores for case matching to ensure group comparability on baseline factors. Intraoperative NG tube use patients and perioperative NG tube use patients were respectively matched to nonuse patients on all available potential confounders. Matched-pairs were identified using propensity scores for 1032 patients with or without intraoperative NG tube use and 176 patients with or without perioperative NG tube use. The incidences of PONV in the intraoperative group were 44.4% vs 41.5% (P = 0.35) with and without tube use, respectively, and 27.8% vs 31.3% (P = 0.61) in the perioperative group. Our results provide evidence that routine use of a NG tube does not reduce the incidence of PONV.
This paper describes a randomized prospective study conducted in 308 patients undergoing caesarean section in spinal anaesthesia at a single hospital between 2010 and 2012 to find a suitable ...anti-emetic strategy for these patients.
Spinal anesthesia was performed in left prone position, at L3/L4 with hyperbaric 0.5% Bupivacaine according to a cc/cm body height ratio. There were no opioids given peri-operatively. The patients received either no prophylaxis (Group I) or tropisetron and metoclopramide (Group II) or dimenhydrinate and dexamethasone (Group III), or tropisetron as a single medication (Group IV). The primary outcome was nausea and/or vomiting (NV) in the intraoperative, early (0-2 h) or late (2-24 h) postoperative period. Multivariate statistical analysis was conducted with a regression analysis and a backward elimination of factors without significant correlation.
All prophylactic agents significantly reduced NV incidence intraoperatively. Relative risk reduction for NV by prophylaxis was most effective (59.5%) in Group II (tropisetron and metoclopramide). In Group III (dimenhydrinate and dexamethasone), NV risk was reduced by 29.9% and by 28.7% in Group IV (tropisetron mono-therapy). The incidence of NV in the early (0?2 h) and the late (2?24 h) postoperative period was low all over (7.8%), but the relative risk reduction of NV in the early postoperative period was 54.1% (Group IV), 45.1% (Group III), and 34.8% (Group II), respectively. In the late postoperative period, there was no significant difference between the 4 groups.
We recommend a prophylactic medication with tropisetron 2 mg and metoclopramide 20 mg for patients during caesarean section. These agents are safe, reasonably priced, and highly efficient in preventing nausea and vomiting.
To compare a full-dose epirubicin-cyclophosphamide (HEC) regimen with classical cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy and with a moderate-dose epirubicin-cyclophosphamide ...regimen (EC) in the adjuvant therapy of node-positive breast cancer.
Node-positive breast cancer patients who were aged 70 years or younger were randomly allocated to one of the following treatments: CMF for six cycles (oral cyclophosphamide); EC for eight cycles (epirubicin 60 mg/m(2), cyclophosphamide 500 mg/m(2); day 1 every 3 weeks); and HEC for eight cycles (epirubicin 100 mg/m(2), cyclophosphamide 830 mg/m(2); day 1 every 3 weeks).
Two hundred fifty-five, 267, and 255 eligible patients were treated with CMF, EC, and HEC, respectively. Patient characteristics were well balanced among the three arms. One and three cases of congestive heart failure were reported in the EC and HEC arms, respectively. Three cases of acute myeloid leukemia were reported in the HEC arm. After 4 years of median follow-up, no statistically significant differences were observed between HEC and CMF (event-free survival EFS: hazards ratio HR = 0.96, 95% confidence interval CI, 0.70 to 1.31, P =.80; distant-EFS: HR = 0.97, 95% CI, 0.70 to 1.34, P =.87; overall survival OS: HR = 0.97, 95% CI, 0.65 to 1.44, P =.87). HEC is more effective than EC (EFS: HR = 0.73, 95% CI, 0.54 to 0.99, P =.04; distant-EFS: HR = 0.75, 95% CI, 0.55 to 1.02, P =.06; OS HR = 0.69, 95% CI, 0.47 to 1.00, P =.05).
This three-arm study does not show an advantage in favor of an adequately dosed epirubicin-based regimen over classical CMF in the adjuvant therapy of node-positive pre- and postmenopausal women with breast cancer. Moreover, this study confirms that there is a dose-response curve for epirubicin in breast cancer adjuvant therapy.
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